Sawako Hyo

A 13-year Study of Japanese Cedar Pollinosis in Japanese Schoolchildren

BACKGROUND Japanese cedar pollen (JCP) sensitization and Japanese cedar pollinosis (JCPS) appear to be increasingly prevalent in younger children. The present study investigated factors affecting JCP sensitization and JCPS development in school children. METHODS In May or June each year from 1994 to 2006, 275-510 children were assessed for serum JCP-IgE and house dust mite (HDM)-IgE levels, and surveyed regarding rhinoconjunctival symptoms. RESULTS Strong JCP sensitization (IgE > or = 17.5 U(A)/ml) was associated with age (odds ratio (OR) = 2.65), the amount of dispersed pollen in the observed year (OR = 2.03) and in the year following birth (OR = 1.51), the month of birth (OR = 2.18), and the recent birth cohort (OR = 1.96). Symptoms were negatively correlated with the recent birth cohort (OR = 0.69) after adjusting for JCP-IgE levels. Strong HDM sensitization was associated with gender (OR = 0.65 for girls) and the recent birth cohort (OR = 1.76). CONCLUSIONS JCP sensitization appeared to be associated with the recent birth cohort and to increases in dispersed pollen just after birth and in the observed season. Although the recent birth cohort was more easily sensitized, they were not more likely to develop symptoms. In contrast to JCP sensitization, strong HDM sensitization appeared to develop prior to commencement of primary school and was more likely to affect boys.

Simultaneous expression of cyclooxygenase-2 and microsomal prostaglandin E synthase in squamous cell carcinoma of the larynx.

Conclusion. In laryngeal cancer, arachidonic acid may be metabolized to PGE2 via the cooperative actions of COX-2 and mPGES, which are induced in response to various stimuli. The COX-2-mPGES-PGE2 system may induce differentiation of cancer cells and prevent metastasis, thus improving the survival rate. Objective. To examine the expression of COX-1, COX-2, and two downstream enzymes – microsomal PGE synthase (mPGES) and PGD synthase (PGDS) – using immunohistochemistry in human laryngeal squamous cell carcinoma (SCC). Patients and methods. Patients with laryngeal carcinoma were referred to the Department of Otolaryngology for treatment. Formalin-fixed, paraffin-embedded laryngeal carcinoma specimens were obtained from 24 patients. Immunohistochemical expression of COX-1, COX-2, mPGES, LPGDS, and HPGDS was investigated in 24 laryngeal carcinoma samples. Results. Among the carcinomas, cytoplasmic immunoreactivity for COX-2 was found in tumor cells in 18 of 24 cases (72%) and that for mPGES in tumor cells in 23 of 24 cases (92%). The localization of mPGES was very similar to that of COX-2. COX-2 in well-differentiated SCCs was higher than in poorly/moderately differentiated SCCs. In terms of lymph node metastasis, there was a significant difference in COX-2 expression.

The efficacy of short-term administration of 3 antihistamines vs placebo under natural exposure to Japanese cedar pollen.

BACKGROUND Japanese cedar pollinosis, a common disease with morbidity of approximately 20% in the Japanese population, is characterized by subjectively irritating symptoms during an annual 3-month period. OBJECTIVE To investigate the effectiveness of cetirizine hydrochloride, loratadine, and fexofenadine hydrochloride in reducing pollinosis symptoms induced while walking in a park during the pollen season. METHODS A randomized, double-masked, placebo-controlled trial was conducted in 113 individuals with Japanese cedar pollinosis during 2 days in March 2003 in Osaka Expo Park, Osaka, Japan. Participants (aged 20-57 years) were divided into 4 groups according to treatment assignment: cetirizine hydrochloride, 10 mg/d; fexofenadine hydrochloride, 120 mg/d; loratadine, 10 mg/d; and placebo (lactose), twice daily. Symptoms were recorded hourly during the study. Furthermore, all the patients completed the Japanese version of the Rhinoconjunctivitis Quality of Life Questionnaire before and after the trial. RESULTS Self-evaluated symptom scores in all 3 active treatment groups showed significant improvements compared with the placebo group. Furthermore, the cetirizine group showed significant improvement in the domains of frequency of nose blowing and nasal obstruction compared with placebo. In addition, improvement in Japanese Rhinoconjunctivitis Quality of Life Questionnaire scores was higher in the cetirizine group than in the loratadine and placebo groups. CONCLUSION Cetirizine seems to be more effective than fexofenadine and loratadine at reducing subjective symptoms in this study population.

Expression of cyclooxygenase-2 and microsomal prostagalandin E synthase-1 in head and neck squamous cell carcinoma

OBJECTIVE Our aim was to examine the expression of COX-2 and microsomal prostaglandin E synthase-1 (mPGES-1), and compare the results with clinical data. PATIENTS AND METHODS Expression of COX-1, COX-2, and mPGS-1 was evaluated by immunohistochemistry in head and neck squamous cell carcinoma (HNSCC) from 25 patients and mRNA levels were determined by the quantitative reverse transcription polymerase chain reaction. RESULTS COX-2 overexpression was noted in tumor cells from 19 of the 25 carcinoma patients and mPGES was expressed by tumor cells from 21 patients. Localization of COX-2 and mPGES-1 was very similar, and well-differentiated tumors showed stronger expression than poorly/moderately differentiated tumors. The COX-2/GAPDH and mPGES/GAPDH mRNA ratios were significantly higher in well-differentiated carcinomas and N0 patients. CONCLUSIONS There was overexpression of COX-2 and its downstream enzyme mPGES-1, and their localization in tumor cells was similar, suggesting that these enzymes play both an important role in the development and proliferation of HNSCC. Furthermore, COX-2 and mPGES-1 were strongly expressed by well-differentiated carcinomas, suggesting their involvement in the differentiation of cancer.

Evaluating the effects of testing period on pollinosis symptoms using an allergen challenge chamber

BACKGROUND We previously built a pollen challenge test unit (allergen challenge chamber: ACC) to collect objective data about Japanese cedar pollinosis. In this study, we investigated adequate conditions for pollen challenge using the ACC. METHODS The study consisted of two parts. The first part was conducted in November, which is not in pollen season. Subjects were exposed to Japanese cedar pollen at a concentration of 50,000 grains/m3 in the chamber for 120 min each day over the course of three consecutive days. The second part was conducted in April, which is just after pollen season. Subjects were exposed to Japanese cedar pollen at the same concentration (50,000 grains/m3) in the chamber for 90 min on a single day. Subjects recorded nasal and ocular symptoms before challenge and every 15 min after challenge initiation. The minimum cross-sectional area in the nasal cavity was measured using acoustic rhinometry before and after challenge as an indicator of nasal obstruction. Inflammatory markers in nasal lavage fluid and serum were also measured before and after challenge. RESULTS Nasal and ocular symptoms were significantly exacerbated after challenge on all days of the single and 3-consecutive-day challenge tests, particularly on the third day of the consecutive challenge test. Nasal and ocular symptoms were also quickly induced with challenge immediately after the end of pollen season. No significant changes in inflammatory markers were seen. CONCLUSIONS Care is needed with regard to pollen challenge conditions in the ACC, including timing of the challenge, to induce pollinosis symptoms that accurately reflect chronic inflammation.

Preliminary study of a challenge test to the patients with Japanese cedar pollinosis using an environmental exposure unit

OBJECTIVE Although clinical studies on pollinosis have been performed employing placebo-controlled double-blind comparative and field techniques, accurate evaluation is difficult because the scattering pollen count and climatic conditions vary between years and regions, leading to a bias in the results. Thus, we prepared a pollen challenge test unit (allergen challenge chamber: ACC) which facilitates quantitative pollen challenge at any time, and, so, the acquisition of objective data. METHODS The control of constant conditions and maintenance of specified pollen concentrations in ACC were investigated. In addition, the pollen distribution in ACC was measured while maintaining the level at 10,000 counts/m(3). The pollen levels were measured employing the aspiration and Durham methods, and the measured values were compared. Furthermore, whether symptoms are adequately induced in the chamber during the non-cedar pollen-scattering season was investigated in 14 volunteers with cedar pollinosis. RESULTS When the pollen level in ACC was set at 6000 counts/m(3) or higher, the rate of variation was +/-15%, within the adjustable range, and that of the pollen distribution in the chamber was within +/-20%. When the volunteers with cedar pollinosis were exposed to cedar pollen in ACC, pollinosis symptoms were induced, and challenge for 2 consecutive days significantly induced symptoms. CONCLUSIONS The temporal and spatial variations of the pollen level in ACC were small, facilitating stable pollen challenge, and pollinosis symptoms were induced in the volunteers with cedar pollinosis. The challenge chamber may be useful to judge the effects of therapy against pollinosis.

Continuous 6-Year Follow-Up Study of Sensitization to Japanese Cedar Pollen and Onset in Schoolchildren

BACKGROUND Intra individual longitudinal data has been lacking for IgE-mediated seasonal allergic rhinitis (SAR), especially in young children. Little is known about the development and natural course of SAR in terms of prevalence and incidence rates in schoolchildren. METHODS In May or June each year from 1994 to 2007, schoolchildren were assessed for serum Japanese cedar pollen (JCP)-IgE and house dust mite (HDM)-IgE levels, and surveyed regarding nasal symptoms. RESULTS Among the 220 children initially assessed in the first grade, 69 (31.4%) were already sensitized to JCP at first grade and 119 (54.1%) did not develop JCP sensitivity during the 6-year study at all. In the first grade children who were HDM-sensitized but JCP non-sensitized, JCP-IgE level was significantly elevated compared to the JCP and HDM non-sensitized group. This seems to indicate that HDM sensitization was very strongly associated with JCP sensitization. CONCLUSIONS Elevated serum IgE is a consequence of specific sensitization to HDM and HDM sensitization appeared to develop prior to the start of primary school which distinguishes HDM sensitization from JCP sensitization.

Allergic Potency of Japanese Cedar Pollen Cry j 1 Is Reduced by a Low Concentration of Hypochlorous Acid Generated by Electolysis

BACKGROUND Although Japanese cedar (Cryptomeria japonica) pollinosis has developed into a health problem, few methods eradicate indoor allergens completely. In a recent study, however, the effectiveness of inactivation with sodium hypochlorite (NaOCl) treatment was revealed. Therefore, the present study aimed to elucidate the ability of chlorine bleach (NaOCl) to reduce the immunogenicity of the major allergenic protein of Japanese cedar (Cry j 1). METHODS Sodium dodecyl sulfate polyacrylamide gel electrophoresis, Western blotting, enzyme-linked immunosorbant assay, and skin testing were carried out in 7 individuals. RESULTS The allergenic protein was undetectable using sodium dodecyl sulfate polyacrylamide gel electrophoresis and silver staining at a sodium hypochlorite/allergenic protein molar ratio of 457. Western blotting with human sera showed the same dose-dependent efficacy. The immunogenicity of the purified protein and cedar pollen was also demonstrated on enzyme-linked immunosorbant assay to be reduced by sodium hypochlorite treatment in a dose- and time-dependent manner. Moreover, sodium hypochlorite-treatment inhibited the skin test response to the protein in all 7 individuals. CONCLUSIONS Hypochlorous acid generated by electrolysis is an effective method for significantly reducing the immunogenicity of Cry j 1.

Interleukin-19 Downregulates Interleukin-4-Induced Eotaxin Production in Human Nasal Fibroblasts

BACKGROUND Interleukin-19 (IL-19), a member of the IL-10 family, is characterized as the cytokine suppressing the release and function of several proinflammatory cytokines. For regulation of local reaction in allergic rhinitis (AR), IL-19 might play an especially important role. METHODS We examined effects of IL-19 on IL-4-induced eotaxin production by human nasal fibroblasts. Early receptor-mediated events (expression of the suppressors of cytokine signaling (SOCS) and phosphorylation of signal transducer and activator of transcription 6 [STAT6]) by IL-19 was examined. Knockdown methods by RNAi were administered to investigate the involvement of those signal transductions. RESULTS Pretreatment with IL-19 downregulates IL-4-induced eotaxin production, but not interferon-γ(IFN-γ)-induced RANTES. Pretreatment with IL-19 suppressed the IL-4-induced STAT6 phosphorylation. The IL-19 induced SOCS-1, but not SOCS-3 or SOCS-5. The SOCS-1 knockdown by RNAi diminished pretreatment with IL-19-induced down-regulation of eotaxin production. CONCLUSIONS These results suggest that IL-19 down-regulates IL-4-induced eotaxin production via SOCS-1 in human nasal fibroblasts. In non-hematopoietic cells in AR, IL-19 might be an immunosuppressive factor.

Expression of cyclooxygenase in laryngeal granuloma

Abstract Objectives: The aim of this study was to elucidate the role of arachidonic acid metabolism in the growth of laryngeal granuloma via the cyclooxygenase pathway. Methods: We examined expression of cyclooxygenase-1 and -2 (COX-1 and COX-2) in laryngeal granuloma in 6 patients. For controls, normal vocal fold in 6 cases were examined in the same method that were obtained from the totally resected larynx because of noninflammatory diseases. Results: Expression of COX2 was observed in the epithelial cells of laryngeal granuloma, however, less expression of COX2 in epithelial cells of the vocal fold. Conclusion: Arachidonic acid metabolism may promote the growth of laryngeal granuloma. This evidence suggests the effectiveness of steroids or NSAIDs in the treatment of laryngeal granuloma.