Nobuo Ohta

Expression of Pendrin Periostin in Allergic Rhinitis Chronic Rhinosinusitis

BACKGROUNDnPendrin and periostin are newly identified mediators of the inflammatory process. The expression of these proteins in human sinonasal tissue and their roles in allergic rhinitis and chronic rhinosinusitis remain to be elucidated. This study investigated the expression of pendrin and periostin in sinonasal tissue of patients with allergic rhinitis, chronic rhinosinusitis, and aspirin-induced asthma. Prospective control study conducted at Yamagata University, Japan.nnnMETHODSnSurgical samples were investigated by means of real-time reverse transcription-polymerase chain reaction to evaluate the expression of pendrin and periostin mRNA. The presence and location of pendrin and periostin were determined by immunohistochemistry and Western blotting.nnnRESULTSnPendrin and periostin production was significantly higher in patients with nasal disorders than in controls. Further significant increases in periostin expression were noted in patients with chronic rhinosinusitis with nasal polyps and in those with aspirin-induced asthma. Immunohistochemistry revealed positive staining for pendrin in epithelial cells and submucosal glands and for periostin in the basement membrane in all three disorders, and additionally for periostin in nasal polyp tissue in chronic rhinosinusitis and aspirin-induced asthma.nnnCONCLUSIONSnProduction of pendrin and periostin is upregulated in allergic rhinitis, chronic rhinosinusitis with nasal polyps, and aspirin-induced asthma. These findings suggest that pendrin can induce mucus production and that periostin can induce tissue fibrosis and remodeling in the nasal mucosa. Therefore, these mediators may be therapeutic target candidates for allergic rhinitis, chronic rhinosinusitis with nasal polyps, and aspirin-induced asthma.

Clinical and pathological characteristics of IgG4-related sclerosing sialadenitis†

A new concept of IgG4‐related sclerosing sialadenitis characterized by high serum IgG4 levels and tissue infiltration of IgG4‐expressing plasmacytes has recently been proposed. To determine appropriate serum levels of IgG4 for monitoring disease activity, a total of 36 serum samples and eight tissue samples from patients with IgG4‐related sclerosing sialadenitis were studied.

Effects and mechanism of OK-432 therapy in various neck cystic lesions

Abstract Conclusion: Our results confirmed that OK-432 therapy is simple, easy, safe, and effective and can be used as a substitute for surgery in the treatment of benign neck cysts. In OK-432 therapy, inflammatory cytokines may play important roles in shrinkage of the cystic spaces. Objective: The aim of this study was to evaluate the outcome and mechanism of action of OK-432 therapy in benign neck cysts. Methods: We tried OK-432 therapy in 83 patients with benign neck cysts between April 1997 and August 2009. We aspirated as much of the fluid content of each cystic lesion as possible, and then replaced the volume of aspirated fluid with about half the volume of OK-432 solution. We evaluated the mechanism of action of OK-432 in 43 of the patients. The intracystic fluid in the cysts was aspirated before and after OK-432 therapy, and cytokine production in each aspirate was analyzed by ELISA. Results: Disappearance of the lesion was observed in 63 of 83 patients (76%). Marked reduction was observed in 13 of the 83 patients (16%). Partial reduction was observed in two patients (2%) and no response was seen in five (6%). Local discomfort at the injection site and low-grade fever were side effects observed in half of the patients, but such problems resolved within a few days. No local scarring or deformity of the injected sites occurred in any patient. We performed OK-432 therapy on an outpatient basis without hospitalization. Levels of various cytokines, including tumor necrosis factor, interleukin-8, interleukin-6, interferon gamma, and vascular endothelial growth factor, were significantly elevated in each aspirate after OK-42 therapy.

Treatments of various otolaryngological cystic diseases by OK-4321: its indications and limitations.

OBJECTIVES/HYPOTHESISnThe aim of this study was to evaluate the indications for, and outcomes and limitations of, OK-432 therapy in various otolaryngological cystic diseases.nnnSTUDY DESIGNnA retrospective clinical study at Yamagata University School of Medicine and the Fukase Clinic in Japan.nnnMETHODSnBetween April 1996 and November 2009 we tried OK-432 therapy in 148 patients with otolaryngological cystic diseases. In cases of plunging ranulas, lymphangiomas, branchial cleft cysts, thyroglossal duct cysts, thyroid cysts, and cervical lymphocele, we aspirated as much of the fluid content of each cystic lesion as possible, and we then replaced the volume of aspirated fluid with about half the volume of OK-432 solution.nnnRESULTSnDisappearance of the lesion was observed in 119 of 148 patients (80%). Marked reduction was observed in 20 of 148 patients (14%). Partial reduction was observed in four patients (3%), and no response was seen in five patients (3%). Plunging ranula, lymphangioma, thyroglossal duct cyst, thyroid cyst, auricular hematoma, and salivary mucocele showed better responses to OK-432 therapy than did branchial cleft cyst. Serious complications with OK-432 therapy were infrequent, and the therapy seemed to have no influence on future surgery.nnnCONCLUSIONSnOur results confirmed that OK-432 therapy is simple, easy, safe, and effective and can be used as a substitute for surgery in the treatment of various otolaryngological cystic diseases.

CD80 (B7-1) and CD86 (B7-2) antigens on house dust mite–specific T cells in atopic disease function through T-T cell interactions

BACKGROUNDnCD80 (B7-1) and CD86 (B7-2) play an important role in antigen presentation to effector cells. Recent studies have demonstrated that these costimulatory molecules are also expressed on activated T cells. However, the functional role of CD80 and CD86 expressed on allergen-specific T cells in atopic diseases has not yet been clarified.nnnOBJECTIVEnWe sought to determine the functional role of CD80 and CD86 expressed on allergen-specific T cells in atopic diseases.nnnMETHODSnWe assayed the expression of CD80 and CD86 on allergen-specific T-cell lines from patients with perennial allergic rhinitis stimulated by Dermatophagoides farinae-crude (Der f-c) antigen, 1 of the major allergens causing house dust mite allergy. T-cell proliferation induced by Der f-c-specific T-T cell interactions was measured, and the role of CD80 and CD86 in this proliferation was examined. In addition, we compared the proportion of CD45RO+CD86(+) T cells in primary culture of PBMCs stimulated by Der f-c antigen between patients with perennial allergic rhinitis and control subjects.nnnRESULTSnOn T-cell activation, CD86 antigen was upregulated earlier than CD80. Both CD80 and CD86 expressed on Der f-c-specific T cells could provide costimulatory signals to induce allergen-specific T-cell proliferation that was partially inhibitable by both anti-CD80 and anti-CD86 mAbs. The proportion of CD45RO+CD86(+) T cells in primary culture from atopic patients was significantly higher than that from control subjects.nnnCONCLUSIONnThese results suggest that costimulatory molecules, such as CD80 and CD86, expressed on allergen-specific T cells may be involved in the amplification of allergen-specific immune responses through T-T cell interactions in atopic diseases.

Roles of IL-17, Th1, and Tc1 Cells in Patients With IgG4-Related Sclerosing Sialadenitis

Immunoglobulin G4 (IgG4)‐related sclerosing sialadenitis is a recently recognized disease entity characterized by high serum IgG4 concentration and IgG4‐producing plasma cell expansion in affected organs, which show fibrotic or sclerotic changes. However, little is known about the roles of CD4+ and CD8+ T cells or interleukin (IL)‐17 in this disease. The purpose of this study was to evaluate the characteristics of CD4+ and CD8+ T cells and IL‐17 in patients with IgG4‐related sclerosing sialadenitis.

Serum levels of soluble adhesion molecules ICAM-1, VCAM-1 and E-selectin in patients with Wegener's granulomatosis

OBJECTIVEnTo examine the role of soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1), and soluble E-selectin (sE-selectin) in the pathogenesis of Wegeners granulomatosis (WG) and the values of measuring serum levels of these soluble adhesion molecules for monitoring disease activity during follow-up, a total of 24 serum samples from 16 patients with WG were studied.nnnMETHODSnThe serum concentrations of soluble adhesion molecules (sICAM-1, sVCAM-1 and sE-selectin) and cytokines (tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6)) of patients with WG were measured by ELISA.nnnRESULTSnThe serum levels of sICAM-1 were significantly elevated in active WG and correlated with disease activity. At the time of relapse, a significant increase of sICAM-1 was also observed. The serum levels of TNF-alpha and IL-6 were also significantly elevated in active WG.nnnCONCLUSIONnThese findings suggest that sICAM-1 plays an important role in the pathogenesis of WG and may be used as an additional parameter of disease activity.

The role of periostin in eosinophilic otitis media

Abstract Conclusion: We investigated the localization of periostin in middle ear specimens from patients with eosinophilic otitis media (EOM) and from a newly constructed animal model for EOM. Periostin-positive immunostaining was observed in the middle ear sections obtained from the EOM patients. Immunoreactivity for periostin was also seen in the animal model. These results suggest that periostin plays an important role in subepithelial fibrosis in the middle ear in EOM. Objective: The purpose of the present study was to investigate the role of periostin in the middle ear of EOM patients and an animal model. Methods: Histological and immunohistochemical analyses for periostin were carried out in the middle ear specimens of six EOM patients with/without asthma. An animal model of EOM was constructed by intraperitoneal and topical sensitization with ovalbumin (OVA). Histological and immunocytochemical analyses for periostin were also performed in this model. Results: Immunoreactivities for periostin were observed in the basement membrane and extracellular matrix of the middle ear sections obtained from all EOM patients with/without asthma. In the animal model, eosinophil infiltration and middle ear mucosa thickness were observed. Moreover, periostin-positive immunostaining was shown in the extracellular matrix of the middle ear mucosa on the side topically boosted by OVA.

Treatment of auricular hematoma by OK-432

Objectives: Intralesional injection therapy with OK-432 was developed as a therapy for operatively difficult lymphangioma (cystic hygroma) and is currently becoming a first-choice treatment for this disease. The aim of this article was to evaluate the outcome and complications of the treatment of patients with auricular hematoma by OK-432 therapy. Study Design: Case series with planned data collection. Setting: Yamagata University School of Medicine. Subjects and Methods: We tried this therapy in 21 patients with auricular hematoma between January 2001 and February 2009. We injected OK-432 solution into the lesion with a 27-gauge needle to prevent the leak of the agent out of the hematoma. We performed this treatment on an outpatient basis without hospitalization. Results: Disappearance or marked reduction of the lesion were observed in all patients who had this therapy, and local scarring and deformity of the auricle did not occur in any patients. As for side effects, local pain at the injection site and fever (37°C-38°C) were observed in a few of the patients who had this therapy, but such problems resolved within a few days. Conclusion: These results may allow us to speculate that intralesional injection therapy with OK-432 is simple, easy, safe, and effective and can be used as a substitute for surgery in the treatment of auricular hematoma.

Analysis of the Comorbidity of Bronchial Asthma and Allergic Rhinitis by Questionnaire in 10,009 Patients

BACKGROUNDnBronchial asthma (BA) and allergic rhinitis (AR) are thought to share a common pathogenesis. However, reports concerning the comorbidity of the two diseases in a large-scaled population are rare in Japan. In the present study, we performed an analysis on the two diseases using questionnaires that addressed the diagnosis, symptoms and period of occurrence in more than 10,000 patients with BA or AR.nnnMETHODSnPatients with BA (adult: n = 2,781, childhood: n = 3,283) and AR (n = 3,945) were enrolled in the present study during the 3 months from August 1, 2006 to October 31, 2006.nnnRESULTSnSixty one percent of the patients with adult BA showed symptoms of AR. Among them, 68% of the patients were diagnosed with AR. Among the patients with childhood BA, 68% showed AR symptoms and 60% were diagnosed with AR. On the other hand, 49% of AR patients showed BA symptoms and 35% of them were diagnosed with BA. The symptoms of both BA and AR in the BA and AR patients were frequent in two seasons, March and April, and September and October. In addition, BA and AR symptoms often co-occurred in the patients with BA and AR.nnnCONCLUSIONSnComorbidity of BA and AR was high in both populations of BA and AR. The symptoms of both BA and AR co-occurred on both a daily and seasonal basis. These results suggested that BA and AR share a common immuno-pathogenesis in the airway and need to be treated as a single airway disease.