Junichiro Ohori

Inhibition of Vascular Endothelial Growth Factor by Macrolides in Cultured Fibroblasts from Nasal Polyps

Objective: In order to study a new mechanism of efficacy of 14‐membered ring macrolides in treating chronic rhinosinusitis, inhibitory effects of macrolides on vascular endothelial growth factor production were examined in vitro.

The role of vascular endothelial growth factor in pediatric otitis media with effusion

OBJECTIVES Vascular endothelial growth factor (VEGF) is a potent and critical inducer of angiogenesis and vascular permeability, and has been shown to play an important role in inflammatory events, together with hypoxia and inflammatory cytokines. VEGF messenger ribonucleic acid (mRNA) is expressed in the middle ear in an experimental animal model of otitis media with effusion (OME) and in patients with OME. However, the protein levels of VEGF in middle ear effusions (MEEs) are unknown and the role of VEGF in the pathogenesis of OME is unclear. The goals of this study were to determine the VEGF levels in MEEs and to investigate the role of VEGF in production of MEEs by comparing these levels with those of interleukin-8 (IL-8), endotoxin, and albumin. METHODS Forty-six MEEs obtained from 33 children (24 boys, 9 girls) were used in the study. The mean age of the subjects was 6.3 years old (range, 1-12 years old). The patients underwent myringotomy and/or insertion of a ventilation tube for treatment of OME. After myringotomy, MEEs were collected with a Juhn Tym-Tap. The samples were divided into serous and mucoid types based on observation by the naked eye. After measuring the weight of the MEE, the sample was diluted with phosphate-buffered saline and frozen until use. The concentrations of VEGF and IL-8 in the MEEs were determined by enzyme-linked immunosorbent assays, endotoxin concentrations were measured by the Limulus Amebocyte Lysate test, and albumin levels were determined using an immunoturbidimetric assay. RESULTS VEGF, endotoxin, IL-8, and albumin were detected in 100%, 89%, 98%, and 100% of the 46 MEEs, respectively. The concentrations of VEGF, endotoxin, and IL-8 were significantly higher in mucoid MEEs than in serous MEEs (p<0.01), whereas there was no significant difference in the albumin concentration between mucoid and serous MEEs. The VEGF levels were positively correlated with those of endotoxin (R(2)=0.17, p<0.05) and albumin (R(2)=0.65, p<0.01) in mucoid MEEs, but not in serous MEEs. CONCLUSIONS Our results suggest that VEGF is produced in response to bacterial components such as endotoxin in the middle ear cavity and is associated with production of mucoid MEEs by increasing serum exudation and mucosal secretion.

Effect of vascular endothelial growth factor on nasal vascular permeability

One of the major functions of vascular endothelial growth factor (VEGF) is increasing vascular permeability. We previously reported that VEGF is present in nasal secretions in rhinosinusitis, particularly in allergic rhinitis, and is hyperproduced immediately after antigen provocation. However, its function in nasal mucosa has not yet been investigated. This study was designed to estimate the increased vascular permeability by VEGF in nasal mucosa and to discuss its possible role in allergic rhinitis.

Vascular endothelial growth factor produced in nasal glands of perennial allergic rhinitis.

Background Vascular endothelial growth factor (VEGF), a pleiotropic polypeptide that mediates endothelial cell-specific responses such as induction of angiogenesis and vascular leakage, is hyperproduced in a variety of inflammatory disorders. In asthma, VEGF hyperproduction promotes mucosal edema by enhancing vascular leakage. However, in allergic rhinitis, details of the pathophysiological importance remain unclear. This study was designed to investigate and discuss the pathophysiological significance of VEGF in nasal secretions from perennial allergic rhinitis sufferers. Methods Seven allergic rhinitis patients sensitized with house-dust mites and 12 chronic rhinosinusitis patients were enrolled. Nasal secretion VEGF was quantified and compared between groups. In allergic rhinitis cases, nasal lavage VEGF was estimated before and after the antigen provocation. Nasal gland VEGF was immunohistochemically investigated. VEGF messenger RNA (mRNA) levels in serous and mucous acini were analyzed by laser microdissection and light cycler-polymerase chain reaction. Results VEGF levels in nasal secretions and nasal lavage from allergic rhinitis were higher than in nonallergic rhinosinusitis, after rather than before antigen provocation. VEGF mRNA expression was higher in serous versus mucous acini. These results are consistent with the immunohistochemistry results. Conclusion In allergic rhinitis, there was significant VEGF production in serous acini, which was hypersecreted after antigen provocation. VEGF may play an important role in pathophysiology of allergic rhinitis.

Clinical classification of peritonsillar abscess based on CT and indications for immediate abscess tonsillectomy

OBJECTIVE To clarify indications for immediate abscess tonsillectomy (IAT) for peritonsillar abscess (PTA). METHODS A retrospective study was performed on 99 patients who were diagnosed with PTA on the basis of computed tomography (CT). Based on CT findings, PTA patients were classified into two categories by abscess shape: Oval type and Cap type. Furthermore, abscess location was differentiated into superior and inferior, resulting in a final classification of 4 categories: superior Oval type; superior Cap type; inferior Oval type; and inferior Cap type. In addition, the proportion of PTA patients showing extraperitonsillar spread into parapharyngeal spaces in each category was examined. RESULTS Superior Oval-type PTA was the most common. Thirteen patients showed extraperitonsillar spread. When CT classifications were compared with clinical findings, patients with inferior Cap-type abscess displayed extraperitonsillar spread more frequently than the other categories of PTA. In all 13 patients, the parapharyngeal space was involved. In addition, 3 patients displayed retropharyngeal space involvement. In all 13 cases, abscess remained above the hyoid bone. CONCLUSIONS Inferior Cap-type PTA may need more intensive and reliable treatment, such as IAT, which might be effective for PTA showing extraperitonsillar spread.

Epithelial-myoepithelial carcinoma of the parotid gland: correlation of dynamic magnetic resonance imaging, 18F-fluorodeoxyglucose-positron emission tomography, and pathological findings

We encountered two cases of epithelialmyoepithelial carcinoma (EMC), a rare low-grade malignant tumor of the parotid gland. These two EMCs showed similar imaging findings: gradual contrast enhancement on dynamic magnetic resonance imaging (MRI), intense 18F-fluorodeoxyglucose (FDG) uptake in the solid tumor portion, and little enhancement and little FDG uptake in the hemorrhagic necrotic tumor portion. When a parotid gland tumor shows gradual MRI contrast enhancement and focally intense FDG uptake, EMC should be included in the differential diagnosis.

Mucosal and systemic immune response to sublingual or intranasal immunization with phosphorylcholine

OBJECTIVE Phosphorylcholine (PC) is a structural component of a wide variety of pathogens including Streptococcus pneumoniae and Haemophilus influenzae. Here, the immune response in mice to PC immunization via the sublingual (SL) route versus the intranasal (IN) route was investigated in terms of efficacy and safety. METHODS BALB/c mice were immunized with PC-keyhole limpet hemocyanin (KLH) plus cholera toxin (CT) or CT alone via the IN or SL route. The immune response generated was studied in terms of PC-specific antibody titers, interferon (IFN)-γ and interleukin (IL)-4 production by CD4+ T cells, and cross-reactivity of PC-specific immunoglobulin (Ig)-A antibodies in nasal washes against S. pneumoniae and non-typeable H. influenzae. RESULTS SL and IN immunization with PC-KLH plus CT resulted in a marked increase in the levels of PC-specific, mucosal IgA and serum IgM, IgG, and IgA antibodies. Additionally, SL immunization elicited significantly higher levels of PC-specific IgG2a subclass antibodies and IFN-γ in serum. On the other hand, IN immunization with CT alone remarkably increased the total IgE level in serum compared with SL and IN immunization with PC-KLH plus CT. PC-specific IgA antibodies in nasal wash samples reacted to most strains of S. pneumoniae and non-typeable H. influenzae. CONCLUSION SL immunization is as effective as IN immunization to induce PC-specific immune responses and more effective than IN immunization to reduce the production of IgE and to prevent the sensitization to allergen causing type I allergy.

Effects of benzalkonium chloride on histamine H1 receptor mRNA expression in nasal epithelial cells.

OBJECTIVE To better understand the causes of the exacerbation of rhinitis medicamentosa (RM) induced by oxymetazoline (OMZ) or benzalkonium chloride (BKC), we examined the impact of pretreatment with OMZ or BKC on cultured human nasal epithelial cells. We also examined the effect of mometasone furoate (MF) on the cultured human nasal epithelial cells treated with OMZ or BKC. METHODS Cells of the human nasal epithelial cell line HNEpC were treated with OMZ or BKC, and the OMZ- and BKC-induced expression of histamine H1 receptor (H1R) mRNA was assayed using real-time polymerase chain reaction. In some experiments, 1.0×10(-5)M MF was added to the HNEpC cells for 24h before treatment with OMZ or BKC. RESULTS Treatment with OMZ slightly increased the expression level of H1R mRNA in HNEpC cells. This enhanced expression was not significantly reduced by pretreatment with MF. In contrast, treatment with BKC remarkably increased the expression level of H1R mRNA in HNEpC cells. In addition, this enhanced expression was significantly reduced by pretreatment with MF. CONCLUSION These results suggest that the increased expression of H1R mRNA due to treatment with OMZ or BKC might be one of the factors underlying the exacerbation of symptoms in patients with RM and those complicated with allergic rhinitis. The concomitant use of a nasal steroid might reduce the exacerbation of symptoms caused by BKC, although there remains a risk of developing histamine hypersensitivity from the long-term use of a topical steroid-containing BKC.

Presence of keratin-specific antibody-forming cells in palatine tonsils of patients with pustulosis palmaris et plantaris (PPP) and its correlation with prognosis after tonsillectomy

Abstract Conclusion: Keratin-specific immune responses in tonsils may be associated with the pathogenesis of pustulosis palmaris et plantaris (PPP). Evaluation of keratin-specific immune responses in tonsils might be useful to predict the effectiveness of tonsillectomy for patients with PPP. Objectives: The aim of the present study was to clarify the role of keratin-specific immune responses in the pathogenesis of PPP in tonsils. It has been reported that anti-keratin antibodies in serum were higher in patients with PPP and decreased after tonsillectomy, indicating that anti-keratin antibodies might be generated in tonsils. Methods: In order to demonstrate the presence of keratin-specific immune responses in tonsils, the numbers of keratin-specific antibody-forming cells (AFCs) in tonsillar and peripheral blood lymphocytes were examined by enzyme-linked immunospot assay. The prognosis of PPP was compared after tonsillectomy. Results: The numbers of keratin-specific IgM and IgG AFCs in tonsils and of IgG AFCs in peripheral blood were significantly increased in patients with PPP. The numbers of keratin-specific IgG AFCs in peripheral blood correlated positively with tonsil and serum IgG antibodies specific to keratin. Our data show that a good prognosis in patients with PPP depended on the numbers of keratin-specific IgG and IgM AFCs in peripheral blood and the levels of keratin-specific IgG antibodies in serum being significantly decreased 6 months after tonsillectomy.

Transcutaneous immunization with pneumococcal surface protein A in mice: Transcutaneous Immunization With PspA

Pneumococcal infection caused by Streptococcus pneumoniae is a major upper respiratory tract disease that causes severe illness and mortality. Therefore, it is important to develop safe and effective vaccines to prevent pneumococcal infections. The goal of the study was to investigate the effectiveness of transcutaneous immunization (TCI) for induction of pneumococcal surface protein A (PspA) responses in the upper respiratory tract.