Dai Takagi

Otologic Manifestations of Wegener's Granulomatosis

Objective/Hypothesis To evaluate the clinical features, treatment, and outcomes of otologic manifestations in Wegeners granulomatosis (WG) treated at Hokkaido University Graduate School of Medicine, Sapporo, Japan.

Clinical study of adenoid cystic carcinoma of the head and neck.

OBJECTIVE We examined prognostic factors and outcome of the primary treatment in patients with adenoid cystic carcinoma (ACC) of the head and neck. METHODS Twenty patients with ACC of the head and neck who had been treated in our institution from 1985 to 1998 were enrolled in this study. Disease-specific survival rate was analyzed by the Kaplan-Mejer method, and the log-rank test was applied to compare the survival rates. RESULTS The overall 5- and 10-year survival rates determined by Kaplan-Meier analysis were 81 and 57%, respectively. Patients with major salivary gland ACC obtained the best 10-year survival rate (83%), while those with paranasal sinus ACC had the worst survival rate (33%). Predominance of the solid component on pathological examination might indicate a worse prognosis. Our study revealed that postoperative radiotherapy could yield better control of the lesion focus. Chemotherapy failed in some patients and was not dramatically effective by itself. CONCLUSIONS The long-term prognosis of ACC was poor. Long-term follow-up is necessary for better prognosis of patients treated with radical treatment regimens.

Nasal manifestations of immunoglobulin G4‐related disease

Immunoglobulin (Ig)G4‐related disease is a systemic syndrome, characterized by sclerosing lesions that mainly affect the exocrine tissue. Although some patients with IgG4‐related disease complain of nasal symptoms, there are few reports concerning the nasal manifestations of this disease. We investigated the clinical and pathological features of the nasal manifestations of IgG4‐related disease.

Immunoregulatory defects of Vα24+Vβ11+ NKT cells in development of Wegener's granulomatosis and relapsing polychondritis

The frequency of either CD4–8– (double negative; DN) or CD4+ Vα24+Vβ11+ NKT cells, the expression of CD1d and the binding of CD1d‐tetramer loaded with α‐galactosylceramide (α‐GalCer) to NKT cells were analysed in peripheral blood mononuclear cells (PBMCs) of patients with Wegeners granulomatosis (WG), relapsing polychondritis (RP) and healthy subjects (HS). DN and CD4+ Vα24+Vβ11+ NKT cells as well as CD1d‐α‐GalCer tetramer‐positive NKT cells, were significantly decreased in number in both WG and RP patients compared to those from HS. When cytokine profiles were analysed in these PBMCs upon stimulation with phorbol ester and calcium ionophore, CD4+ T cells from patients with WG and RP exhibited a Th1 bias, whereas CD4+ NKT cells from WG patients in remission showed a Th2 bias. These findings suggest that NKT cells (especially CD4+ NKT cells) play a regulatory role in Th1 autoimmunity in patients with WG and RP. The reduction in NKT cell counts appears to be associated with the low responsiveness to α‐GalCer. The dysfunction of NKT cells to recognize ligands such as α‐GalCer may also contribute to the defects observed in NKT cells from WG and RP patients.

Preservation of the nasolacrimal duct during endoscopic medial maxillectomy for sinonasal inverted papilloma.

BACKGROUND To assess the efficacy of a new endonasal medial maxillectomy technique (EMM) for the treatment of inverted papilloma (IP). METHODOLOGIES A prospective series of 55 consecutive patients diagnosed with IP between March 2002 and April 2009 were entered into this study. The new surgical technique was applied to tumors arising from the anterior part of the maxillary sinus. After conventional EMM, the entire nasolacrimal duct was separated from the bony component of the nasolacrimal canal and preserved. Schirmer`s test and a visual analog scale (VAS) score were used to assess the lacrimal duct function after surgery. RESULTS Ten of the 55 patients underwent the new surgical procedure. All patients were categorized with stage T3 or T4 tumors. No patients suffered tumor recurrence. There was no difference in lacrimal duct function between the diseased side and healthy side of the nasolacrimal duct. The mean VAS score was 2.8/100. CONCLUSIONS This new surgical technique preserves the whole length of the nasolacrimal unit. It also offers several advantages including good visualization, nasolacrimal function after surgery and fewer adverse effects such as facial numbness and epiphora.

TRIM39 negatively regulates the NFκB-mediated signaling pathway through stabilization of Cactin

NFκB is one of the central regulators of cell survival, immunity, inflammation, carcinogenesis and organogenesis. The activation of NFκB is strictly regulated by several posttranslational modifications including phosphorylation, neddylation and ubiquitination. Several types of ubiquitination play important roles in multi-step regulations of the NFκB pathway. Some of the tripartite motif-containing (TRIM) proteins functioning as E3 ubiquitin ligases are known to regulate various biological processes such as inflammatory signaling pathways. One of the TRIM family proteins, TRIM39, for which the gene has single nucleotide polymorphisms, has been identified as one of the genetic factors in Behcet’s disease. However, the role of TRIM39 in inflammatory signaling had not been fully elucidated. In this study, to elucidate the function of TRIM39 in inflammatory signaling, we performed yeast two-hybrid screening using TRIM39 as a bait and identified Cactin, which has been reported to inhibit NFκB- and TLR-mediated transcriptions. We show that TRIM39 stabilizes Cactin protein and that Cactin is upregulated after TNFα stimulation. TRIM39 knockdown also causes activation of the NFκB signal. These findings suggest that TRIM39 negatively regulates the NFκB signal in collaboration with Cactin induced by inflammatory stimulants such as TNFα.

Clinical features of bilateral progressive hearing loss associated with myeloperoxidase-antineutrophil cytoplasmic antibody.

In this study, we analyzed the clinical features, diagnostic criteria, treatment, and outcome of atypical bilateral progressive hearing loss associated with myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA). The evaluation was made by audiogram and laboratory data in 6 cases treated at Hokkaido University Hospital. We measured MPO-ANCA by enzyme-linked immunosorbent assay; the result was positive in all cases. The hearing loss developed bilaterally and progressed to total deafness within several weeks. The onset of hearing loss was not simultaneous in the 2 ears. Methylprednisolone pulse therapy was effective in 9 ears. Three ears showed no improvement; 2 of the 3 ears had already exhibited total deafness at the first visit. After the treatment. the titer of MPO-ANCA decreased in all patients. The level of MPO-ANCA should be tested in patients with bilateral progressive hearing loss of unknown origin and can be used as a marker of the diseases activity.

Otologic Manifestations of Immunoglobulin G4-Related Disease:

Objective: Immunoglobulin (Ig) G4-related disease is systemic, and it has been reported that patients with IgG4-related disease complain of symptoms involving numerous organs. However, there are few reports concerning the otologic manifestations of IgG4-related disease. The purpose of this study is to investigate the clinical features of the otologic manifestations in IgG4-related disease. Methods: We recruited 39 consecutive patients diagnosed with IgG4-related disease. Otologic symptoms, laboratory data, and audiogram findings were retrospectively examined. Mucosal tissues from the inferior turbinate were obtained from subjects before treatment. The serum IgG4 and eosinophil levels together with clinical features were analyzed. Results: Five of the 39 cases had some otologic symptoms. Otitis media with effusion was present in 2 patients. Sensorineural hearing loss was also present in 1 patient. Eosinophilic otitis media was present in 2 patients with bilateral rhinosinusitis and bronchial asthma, and elevated serum eosinophil levels. Oral prednisolone was effective in the treatment of IgG4-related disease. Conclusion: We revealed a new clinical entity associated with the otologic manifestations of IgG4-related disease.

Macrophage migration inhibitory factor in allergic rhinitis: its identification in eosinophils at the site of inflammation.

The aim of this study was to assess the potential role of macrophage migration inhibitory factor (MIF) in the pathogenesis of allergic rhinitis (AR). Serum MIF concentrations were measured by a specific enzyme-linked immunosorbent assay. In order to elucidate the cellular source of MIF, we performed double immunostaining of biopsy specimens of the nasal mucous membrane with markers for MIF and for inflammatory cells. The mean MIF level in sera from patients with AR was significantly higher than that in sera from healthy controls. Moreover, the levels were significantly correlated with the severity of the clinical symptoms. The majority of the MIF-positive cells at the site of allergic inflammation were eosinophils. These data suggest that MIF plays a role in the initiation and maintenance of AR. Eosinophils formed the largest population of MIF-producing cells; this finding suggests that they may be a major source of MIF at inflammatory sites in atopic disease.

Otolaryngologic Manifestations of Antineutrophil Cytoplasmic Antibody–Associated Vasculitis

Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis is characterized by systemic necrotizing vasculitis, and patients fall into 2 groups: those with proteinase 3–ANCA and those with myeloperoxidase-ANCA. As infections are a trigger of ANCA-associated vasculitis, this disease tends to localize in areas around the upper airway. In this study, the authors compared ear and nasal symptoms between patients with proteinase 3–ANCA and those with myeloperoxidase-ANCA. We undertook a retrospective case series study of 34 patients diagnosed with ANCA-associated vasculitis. The otologic symptoms were divided into 3 types: chronic otitis media, secretory otitis media, and sensorineural hearing loss. Chronic otitis media was more common in patients with proteinase 3–ANCA (P = .001), whereas secretory otitis media was more frequently found in patients with myeloperoxidase-ANCA (P = .007). Crust formation (P = .001), saddle nose (P = .024), and sinusitis (P = .001) were more common in patients with proteinase 3–ANCA than in those with myeloperoxidase-ANCA. Marked differences were observed in the disease spectrum between the 2 ANCA groups.