Search

We developed novel closo -dodecaborate ([B 12 H 11 ] 2- ) anion-containing translocator protein (TSPO) ligand as a boron carrier for boron neutron capture therapy. This compound shows high water solubility and can deliver boron to TSPO highly expressed in breast cancer cells. We describe the synthesis and in vitro evaluation of a dodecaborate-based pyrazolopyrimidine., Competing Interests: The authors declare no competing financial interest., (© 2021 American Chemical Society.)

Hydrolysates of an emetic toxin cereulide were found in the broth of Bacillus cereus. The ester cleaved depsipeptides of cereulide were synthesized using liquid phase fragment condensation method starting from commercially available amino acids. The chemical structure of hydrolysates was verified tetradepsipeptide l-O-Val-l-Val-D-O-Leu-d-Ala and dodecadepsipeptide (D-O-Leu-d-Ala-l-O-Val-l-Val) 3 using LC-TOFMS. Quantitative analysis of cereulide in the broth revealed production of cereulide in the stationary phase and decomposition in the death phase. The increase in tetradepsipeptide continued after the stationary phase until decomposition occurred., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: We performed a follow up study about willingness and behaviors to quit smoking among smokers with schizophrenia in Japan., Methods: Participants were outpatients with schizophrenia aged 20-69 years who had been visiting the hospital for ≥1 year as of April 1, 2016, and had visited the hospital more than once in the previous 6 months. A baseline survey on smoking behaviors including current smoking status and smoking cessation stage, was administered in 420 participants that were randomly extracted from a patient pool (n = 680) in 2016, and a follow-up survey was administered in 2017. We calculated the distribution and change in smoking cessation stage, number of smokers and nonsmokers after 1 year, and quitting rate from a naturalistic 1-year smoking-cessation follow up., Results: The number of baseline respondents was 350; 113 current smokers and 68 former smokers. Among the 113 current smokers, 104 (92.0%) were followed for 1 year, 79 (70.0%) were interested in smoking cessation, and only 7 had received smoking cessation treatments at baseline. Among the tracked 104 participants, only 6 (5.8%) stopped smoking after 1 year. Among the 25 participants who had intentions to quit smoking within 6 months at baseline, 6 (24.0%) maintained their intention to quit smoking for 1 year, and 16 (64.0%) did not maintain their intention to quit smoking., Conclusions: Our findings showed that many smokers with schizophrenia were interested in quitting smoking, but few patients received treatment and actually quit smoking. Timely intervention, including the option to receive smoking cessation treatment, is necessary for those patients with schizophrenia who smoke., Trial Registration: UMIN Clinical Trials Registry (UMIN000023874, registered on August 31, 2016).

Homocereulide, isolated from marine bacterium Bacillus cereus, is an analog of emetic toxin cereulide. There is no report on its structure determination and involvement in B. cereus-associated food poisoning. Homocereulide is a cyclic dodecadepsipeptide composed of l-O-Val-l-Val-d-O-Leu-d-Ala and l-O-allo-Ile-d-Val-d-O-Leu-d-Ala. Here, we synthesized homocereulide using liquid phase fragment condensation. The NMR spectrum of synthesized homocereulide confirmed the intended structure and LC-MS results were consistent with natural products. Morphological evaluation using HEp-2 cells showed higher toxicity with homocereulide (1.39 nM) than cereulide (3.95 nM). Though cereulide is the main component in broth culture, homocereulide is also likely involved in B. cereus-associated food poisoning., (Copyright © 2019. Published by Elsevier Ltd.)

There was a significant amount of non-specific, but not of allergen (e.g., papain, mite feces and four kinds of pollen)-specific, IgE antibodies (Abs) in the sera of normal mice. An i.n. injection of each allergen without adjuvant into mice caused an increase in total IgE Ab titers with a similar time course in the serum. However, the stage of initiation of allergy varied from allergen to allergen. Submandibular lymph node cells from normal mice contained papain-, but not mite feces- or pollen-specific IgE + cells and an i.n. injection of papain induced papain-specific IgE Abs in the serum. In contrast, one (i.n.) or two (i.n. and s.c) injections of mite feces induced neither mite feces-specific IgE + cells in the lymph nodes nor mite feces-specific IgE Abs in the serum. I.n. sensitization with cedar pollen induced cedar pollen-specific IgE + small B cells in the lymph nodes on Day 10, when non-specific IgE Ab titers reached a peak in the serum, implying induction of related allergen-specific IgE + small cells as well. In fact, a second (s.c.) injection of ragweed (or cedar) pollen into mice sensitized i.n. once with cedar (or ragweed) pollen, but not with mite feces, induced a large amount of ragweed (or cedar) pollen-specific IgE Abs in the serum. These results indicate that when firstly-sensitized non-specific IgE + small B cells in mouse lymph nodes include some secondly-sensitized allergen-specific ones, mice produce IgE Abs specific for the secondly-injected allergen., (© 2018 The Societies and John Wiley & Sons Australia, Ltd.)

We report a case of unnoticed pregnancy that was maintained during low estrogen and progesterone circumstances, that showed menses-like bleeding, and was then discovered after ovarian hyperstimulation during the next period. The patient was 39 years old and primigravid. She underwent intrauterine insemination, followed by luteal support with human chorionic gonadotrophin and progestin; however, she experienced menstruation-like bleeding 15 days later. As low estradiol and progesterone levels were confirmed on the 2nd day of bleeding, ovarian hyperstimulation of short protocol for in vitro fertilization was commenced. Although 13 mature follicles were observed, only six oocytes were retrieved and one developed into a blastocyst. Four days after oocyte pick-up, a gestational sac was seen in utero. The fetus is currently growing uneventfully. This case suggests that pregnancy can be maintained during ovarian hyperstimulation, even if menstruation-like bleeding is shown in low-progesterone circumstances., (© 2016 Japan Society of Obstetrics and Gynecology.)

Long-period ground motions in plain and basin areas on land can cause large-scale, severe damage to structures and buildings and have been widely investigated for disaster prevention and mitigation. However, such motions in ocean-bottom areas are poorly studied because of their relative insignificance in uninhabited areas and the lack of ocean-bottom strong-motion data. Here, we report on evidence for the development of long-period (10-20 s) motions using deep ocean-bottom data. The waveforms and spectrograms demonstrate prolonged and amplified motions that are inconsistent with attenuation patterns of ground motions on land. Simulated waveforms reproducing observed ocean-bottom data demonstrate substantial contributions of thick low-velocity sediment layers to development of these motions. This development, which could affect magnitude estimates and finite fault slip modelling because of its critical period ranges on their estimations, may be common in the source areas of subduction earthquakes where thick, low-velocity sediment layers are present.

The detection of boron-containing compounds requires very expensive facilities and/or tedious sample pretreatments. In an effort to develop a convenient detection method for boronic acid derivatives, boron chelating-ligands were synthesized for use as fluorescent sensors. In this paper, the synthesis and properties of fluorescent sensors for boronic acid derivatives are reported.

Purpose: To determine the prevalence of insulin resistance (IR) and impaired glucose tolerance (IGT) in PCOS patients, the optimal screening method, and to compare our findings between nonobese and obese Japanese women with PCOS., Methods: Ninety-eight PCOS patients were included in this research from 2006 to 2013. Glucose tolerance test (OGTT) was performed. Serum glucose and insulin concentration were assayed before and 30, 60, and 120 min after taking 75 g of glucose., Results: All examined metabolic parameters were significantly favorable in the nonobese subjects, below 25 kg/m 2 . HOMA-IR, fasting insulin, glucose 120 , and insulin 120 showed strong correlations with BMI. A total of 1.4 % of nonobese women had IR based on fasting insulin or HOMA-IR. However, 15.5 % (11/71) of nonobese women had IR as determined by a continuous increase of serum insulin level in OGTT. In comparison, the prevalence of IR among the obese women ranged from 41 to 59 %. AUC glucose , glucose 60 , glucose 120 , and insulin 120 in nonobese women with a continuous insulin increase were higher than those without such a continuous increase., Conclusions: All examined metabolic parameters were significantly correlated with BMI. As the presence of a continuous increase of insulin level reflects to some degree poorer glucose tolerance, delayed insulin secretion, and enhanced insulin response compared with non-continuous insulin increase, OGTT might not been excluded to determine IR and IGT for nonobese women with PCOS., Competing Interests: H. Negishi, K. Nakao, M. Kimura, H. Takenaka, and M. Horikawa declare that they have no conflicts of interest.

Boron-neutron capture therapy (BNCT) is an attractive technique for cancer treatment. As such, α, α-cycloalkyl amino acids containing thiododecaborate ([B12H11](2-)-S-) units were designed and synthesized as novel boron delivery agents for BNCT. In the present study, new thiododecaborate α, α-cycloalkyl amino acids were synthesized, and biological evaluation of the boron compounds as boron carrier for BNCT was carried out.

Like asthma and atopic dermatitis, allergic rhinitis is an allergic disease, but of the three, it is the only type I allergic disease. Allergic rhinitis includes pollinosis, which is intractable and reduces quality of life (QOL) when it becomes severe. A guideline is needed to understand allergic rhinitis and to use this knowledge to develop a treatment plan. In Japan, the first guideline was prepared after a symposium held by the Japanese Society of Allergology in 1993. The current 7th edition was published in 2013, and is widely used today. To incorporate evidence based medicine (EBM) introduced from abroad, the most recent collection of evidence/literature was supplemented to the Practical Guideline for the Management of Allergic Rhinitis in Japan 2013. The revised guideline includes assessment of diagnosis/treatment and prescriptions for children and pregnant women, for broad clinical applications. An evidence-based step-by-step strategy for treatment is also described. In addition, the QOL concept and cost benefit analyses are also addressed. Along with Allergic Rhinitis and its Impact of Asthma (ARIA), this guideline is widely used for various clinical purposes, such as measures for patients with sinusitis, childhood allergic rhinitis, oral allergy syndrome, and anaphylaxis and for pregnant women. A Q&A section regarding allergic rhinitis in Japan was added to the end of this guideline.

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.

Like asthma and atopic dermatitis, allergic rhinitis is an allergic disease, but of the three, it is the only type I allergic disease. Allergic rhinitis includes pollinosis, which is intractable and reduces quality of life (QOL) when it becomes severe. A guideline is needed to understand allergic rhinitis and to use this knowledge to develop a treatment plan. In Japan, the first guideline was prepared after a symposium held by the Japanese Society of Allergology in 1993. The current 7th edition was published in 2013, and is widely used today. To incorporate evidence based medicine (EBM) introduced from abroad, the most recent collection of evidence/literature was supplemented to the Practical Guideline for the Management of Allergic Rhinitis in Japan 2013. The revised guideline includes assessment of diagnosis/treatment and prescriptions for children and pregnant women, for broad clinical applications. An evidence-based step-by-step strategy for treatment is also described. In addition, the QOL concept and cost benefit analyses are also addressed. Along with Allergic Rhinitis and its Impact of Asthma (ARIA), this guideline is widely used for various clinical purposes, such as measures for patients with sinusitis, childhood allergic rhinitis, oral allergy syndrome, and anaphylaxis and for pregnant women. A Q&A section regarding allergic rhinitis in Japan was added to the end of this guideline., (© 2014 Japanese Society of Allergology.)

Although the outcomes of various treatment modalities for vitiligo have been studied extensively, the influence of the participant's characteristics on treatment response has not been thoroughly investigated. Therefore, we retrospectively investigated treatment effects and their association with clinical characteristics in Japanese patients with vitiligo. The charts of patients with vitiligo treated in our institution were reviewed. Clinical response was evaluated as a marked response rate, defined as repigmentation in >75% of the initial lesional area. 162 patients were treated with phototherapy, while 69 were treated with topical mono-therapy. The patients treated with phototherapy and those treated with both phototherapy and topical treatment demonstrated significantly higher clinical response rates compared to patients treated solely with topical mono-therapy (marked response rate: 19.1% vs. 5.8%, P<0.05; and 23.5% vs. 5.8%, P<0.01, respectively). Among the phototherapy-treated patients, younger subjects (≤15 years old) were more responsive to phototherapy compared to older patients (37.0% vs. 15.6%; P=0.015). The disease subtypes did not affect treatment response. In conclusion, phototherapy appears to have a therapeutic effect superior to topical mono-therapy on both focal and generalized vitiligo, especially in younger patients. Thus, any type of psychosocially devastating lesions in a pediatric patient may be a good target for phototherapy.

Objective: The assessment of asthma control is pivotal to treatment decisions. A questionnaire that assesses the Global Initiative for Asthma (GINA)-defined control requires four questions. A visual analog scale (VAS) to evaluate asthma control can be simply marked, but its correlation with GINA-defined control has been insufficiently evaluated. The purpose of this study is to evaluate whether VAS levels can predict GINA-defined asthma control with particular emphasis on the distinctions between "partly controlled" and "uncontrolled" and between "partly controlled" and "controlled" asthma,, Methods: A cross-sectional multicenter study was carried out throughout Japan (SACRA) from March to August 2009 among patients with a diagnosis and treatment of asthma. Asthma control was studied using the GINA questionnaire and a VAS measurement of asthma severity. Pulmonary function testing was not carried out,, Results: 1910 physicians enrolled 29,518 patients with asthma. 15,051 (51.0%) questionnaires were administered by physicians; patients filled out 14,076 (47.7%) questionnaires themselves. 28,225 (95.6%) of the patients were evaluable. VAS measurement of asthma symptoms was useful in predicting levels of GINA-defined control categories (the area under the receiver operating characteristic curve ranging from 0.704 to 0.837). Patients with "controlled," "partly controlled," and "uncontrolled" asthma were discriminated by VAS levels (1.50, 4.79, and 7.19). Similar results have been obtained with self- and physician-administered questionnaires showing the validity of results., Conclusion: Measurement of VAS levels is able to discriminate between patients with "controlled," "partly controlled," and "uncontrolled" asthma. The VAS score could be a simple guide in clinical situations requiring daily or regular evaluation of asthma control.

Many countries throughout the world have experienced an increase in the prevalence of allergic rhinitis (AR), which has come to be a major cause of morbidity in developed countries. The pathology underlying AR is regarded as IgE-mediated type I allergy characterized by mucosal inflammation that occurs in response to allergen exposure. In Japan, AR caused by Japanese cedar pollen, the most common allergic disease, has become a salient public health challenge. Almost all primary care physicians and otorhinolaryngologists have been consulted by AR patients between February and April. Although most such patients have received treatment, numerous patients with AR have not received proper examinations for AR. Clinical guidelines are systematically developed statements that are designed to help practitioners make decisions about appropriate and effective health care. Guidelines in many countries including Japan have been published for AR. Unfortunately, those guidelines have remained untested. Moreover, they might be difficult for non-specialists to use. In this review, we specifically examine the present standard examination for diagnosis of AR and optimal classification for AR in Japan. We hope that this review would be used not only for the support of daily practice but also for selection of AR patients for clinical trials., (Copyright © 2012. Published by Elsevier Ireland Ltd.)

The production of allergen-specific IgE antibodies (Abs) in allergen-sensitized patients or animals has a mutual relationship with the immunologic response leading to allergic rhinitis. We recently reported that, after an intranasal injection of cedar pollen into mice, an interleukin-4 (IL-4)-dependent increase in serum nonspecific IgE Abs was a prerequisite for the production of serum allergen-specific IgE Abs. Here, we explored which lymphoid organs were responsive to the intranasally injected allergen and how IL-4 and IgE Abs were produced in the lymphocytes. Time-dependent changes in the total cell numbers and in in vitro IgE Ab production in various lymphoid organs revealed that the submandibular lymph nodes were the main responsible organ. After treatment with allergen (for IgE production) or allergen and complete Freund's adjuvant (for IgG production), we separated submandibular lymph node cells into macrophage-, lymphocyte-, and granulocyte-rich populations by discontinuous Percoll density-gradient centrifugation. Unexpectedly, bulk cells, but not the lymphocyte- or macrophage-rich populations, produced significant amounts of IL-4, IgE, and IgG; whereas production was restored by addition of Mac-1(+) cells from the macrophage-rich to the lymphocyte-rich fraction. Furthermore, a combination of the lymphocyte-rich population (for IgG [or IgE]) production) and the macrophage-rich population (for IgE [or IgG]) production) produced a large amount of IgE (or IgG). These results indicate that, in the initiation of allergic rhinitis, macrophages in the submandibular lymph nodes are essential not only for IL-4 or immunoglobulin production, but also for class switching of immunoglobulin in lymphocytes., (© 2012 The Societies and Blackwell Publishing Asia Pty Ltd.)

Wound healing is a sophisticated biologic process. In the case of hemithyroidectomy, the operation time is relatively short with small tissue damage and without skin excision, and bacterial contamination before, during, and after the operation is uncommon. Here, we explored which cytokine(s) affected the rates of healing of skin wounds after hemithyroidectomy of 29 patients. We assessed the amounts of cytokines (e.g., interleukin-6, platelet-derived growth factor, basic fibroblast growth factor, vascular endothelial growth factor, and tumor necrosis factor-α) in either the preoperative or postoperative lavage fluids, or in the drainage fluids on postoperative days (PODs) 1-8. All of these cytokines showed a similar pattern; after reaching a peak on POD1, the production fell sharply on POD2-8, revealing that wound healing commenced on POD1. The rates of wound healing were inversely related to the levels of histamine in six patients (i.e., those with the three largest and those with the three smallest total volumes of drainage fluid on POD1): high (or low) levels of histamine in the postoperative lavage fluids with low (or high) levels in the drainage fluids on POD1 caused earlier (or the delay of) wound healing, suggesting involvement of histamine in the acceleration and delay of wound healing., (© 2012 by the Wound Healing Society.)

Background: The relationship between chronic rhinosinusitis (CRS) and asthma has been known for a long time. However, no large studies on the relationship between CRS and lower airway diseases have been reported to date in Japan. Additionally, eosinophilic chronic rhinosinusitis (ECRS) in Japan is considered to be a subgroup of CRS with nasal polyps (CRSwNP) characterized by eosinophil-dominant inflammation. However, the diagnostic criteria of ECRS have not been established., Methods: To investigate clinical and epidemiological features of patients with CRS from the aspect of their associations with lower airway diseases, 553 patients with CRS who visited one of six local university hospitals were examined and interviewed. Local eosinophilic infiltration was evaluated pathologically by examining NPs., Results: The prevalences of olfactory dysfunction (OD) in the patients with nasal polyps (NPs) and those without NPs were 57.0% and 13.7%, respectively (p < 0.0001). The prevalence of asthma in all patients was 23.1%. Furthermore, the prevalences of NPs and OD in the patients with asthma and those without asthma were 81.0% and 50.1% (p < 0.0001) and 64.2% and 35.7% (p < 0.0001), respectively. 97.4% of the patients with asthma had ≥ 15% mucosal eosinophils, and 87.9% of the patients without asthma had <15% mucosal eosinophils., Conclusions: Similar to the relationship between nasal allergy and asthma, CRSwNP may be applicable to the concept of "one airway, one disease".

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.

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.

Like asthma and atopic dermatitis, allergic rhinitis is an allergic disease, but of the three, it is the only type I allergic disease. Allergic rhinitis includes pollinosis, which is intractable and reduces quality of life (QOL) when it becomes severe. A guideline is needed to understand allergic rhinitis and to use this knowledge to develop a treatment plan. In Japan, the first guideline was prepared after a symposium held by the Japanese Society of Allergology in 1993. The current 6th edition was published in 2009, and is widely used today. To incorporate evidence based medicine (EBM) introduced from abroad, the most recent collection of evidence/literature was supplemented to the Practical Guideline for the Management of Allergic Rhinitis in Japan 2009. The revised guideline includes assessment of diagnosis/treatment and prescriptions for children and pregnant women, for broad clinical applications. An evidence-based step-by-step strategy for treatment is also described. In addition, the QOL concept and cost benefit analyses are also addressed. Along with Allergic Rhinitis and its Impact of Asthma (ARIA), this guideline is widely used for various clinical purposes, such as measures for patients with sinusitis, childhood allergic rhinitis, oral allergy syndrome, and anaphylaxis and for pregnant women.

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., (Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.)

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., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)

The aim of this study is to investigate the clinical and pathological characteristics of basal cell adenoma (BCA) and to compare the diagnosis/treatment of BCA with those of Warthin's tumor (WT) and pleomorphic adenoma (PA). Among 192 patients with benign tumors of the parotid gland who underwent surgery, 9 had BCA. All of these tumors showed a benign pattern on computed tomography and magnetic resonance imaging. The accuracy of fine needle aspiration biopsy (FNAB) for diagnosis of BCA was slightly lower than for PA and WT. Most PA and BCA lesions developed in the upper part of the parotid gland. Considering the gender difference, tumor site, and age, it is necessary to differentiate BCA from PA rather than from WT. There were no significant differences in the duration of surgery, the blood loss, and the incidence of transient facial paralysis between surgical resection of BCA and surgery for PA or WT. BCA is the third most common of the benign parotid tumors, following WT and PA, although its incidence is low. When PA and WT are ruled out by FNAB after a tentative diagnosis of benign tumor has been based on imaging findings, BCA should be considered.

Conclusion: The novel midline electroneurography (ENoG) method may have advantages over the standard method in terms of ease of electrode setting, and the ENoG value may be a useful prognostic factor., Objective: We compared ENoG performed in patients with facial palsy using two different methods--the new midline method and standard method--in terms of the amplitudes of the compound muscle action potentials(CMAPs) and relationship between the ENoG value and clinical course., Methods: A total of 64 patients with facial palsy were enrolled. CMAPs were recorded using the midline method, in which the recording electrodes were placed on the mental protuberance and philtrum over the orbicularis oris muscle, and the standard method, in which the recording electrodes were set close to the nasolabial fold. Percutaneous electrical stimulation was applied to the main trunk of the facial nerve.The amplitudes of the CMAPs and the relationship between the ENoG value and the period to full recovery from the facial palsy were compared., Results: The midline method had larger CMAP amplitudes on both sides and a stronger negative correlation in the relationship between the ENoG value and period to full recovery from palsy than the standard method statistically.

Conclusions: Elective neck dissection (END) may not be necessary in patients with low-grade malignancy. However, currently, END should be performed in all patients with parotid carcinoma because the preoperative diagnosis of lymph node metastasis is limited and the accuracy of preoperative grade diagnosis is low., Objective: Our aim was to examine the indication for END in N0 patients and the extent of dissection by investigating the accuracy of diagnosing the grade and lymph node metastasis of parotid carcinoma., Patients and Methods: The subjects were 77 patients with parotid carcinoma. Among N0 patients, modified radical neck dissection (MRND) was conducted in those in whom the histological grade was evaluated as high, and selective neck dissection (SND) in other patients., Results: Lymph node metastasis was detected in 27 of 71 patients who underwent neck dissection. Node metastasis was detected in 19 (61.3%) of 31 patients in whom high-grade malignancy was suggested and in 8 (22.9%) of 35 patients in whom intermediate-grade malignancy was suggested preoperatively. There was no metastasis in any of the five patients in whom low-grade malignancy was suggested. Occult metastasis was noted in 8 of 51 patients. The rate at which the histological grade was accurately diagnosed before surgery was low, especially in patients with low-grade malignancy.

Conclusion: Considering the incidence of metastasis from papillary thyroid carcinoma (PTC) with respect to the lateral cervical regions and limited detection on preoperative ultrasonography (US), level II to IV dissection may be essential when lateral node metastasis (LNM) is detected on preoperative US., Objectives: LNM is frequent in patients with PTC. However, a consensus regarding its preoperative diagnosis and the indication/extent of lateral node dissection (LND) has not been reached. We prepared criteria for diagnosing LNM from PTC using US. Furthermore, we investigated the usefulness and limits of US and appropriate extent of dissection., Patients and Methods: We conducted a retrospective study in 70 patients with PTC (80 sides) in whom LNM was detected preoperatively, and level II to V LND was performed. We compared the results of the preoperative diagnosis of LNM using US in accordance with the criteria with those of histopathological diagnosis after LND., Results: Diagnostic criteria for LNM were a minor axis of 6 mm or more and a minor/major axis ratio of 0.5 or more. Histopathologically, metastasis was detected in 467 lymph nodes. Of these, 199 (43%) were detected on US, and met the diagnostic criteria.

Simultaneous activation of murine mast cells by monomeric IgE and toll-like receptor (TLR) ligands was examined. Inflammatory cytokine production elicited by the binding of IgE in the absence of antigen, was further enhanced by the addition of lipopolysaccharide (LPS) or peptidoglycan (PGN). Enhancement by LPS or PGN on cytokine production was mediated by TLR4 and TLR2, respectively, since TLR4- and TLR2-deficient mast cells did not show synergistic activation by monomeric IgE and LPS/PGN. Synergistic activation of mast cells was obtained via phosphorylation of several mitogen-activated protein kinases (MAPK). Furthermore, MAPK inhibitors, significantly attenuated the augmentation of inflammatory cytokine production by monomeric IgE and LPS or PGN. Altogether, these results suggest that simultaneous TLR activation of mast cells with IgE molecules, particularly highly cytokinergic (HC) IgE, might contribute to the exacerbation of allergic diseases associated with infection even in the absence of a specific antigen., (Copyright 2009 Elsevier Inc. All rights reserved.)

Objectives/hypothesis: We present the case of a 21-year-old woman who underwent endoscopy-assisted surgery with topical mitomycin for a large cholesterol granuloma in the petrous apex that involved the eustachian tube., Study Design: Case report., Methods: Minimally invasive surgery was performed on the cholesterol granuloma with endoscopic assistance, and topical mitomycin (0.4 mg/mL) was administered to prevent scarring of the newly created drainage/ventilation route. With the endoscopic approach, the drainage/ventilation route was secured not only from the tympanic cavity, but also using a guidewire inserted from the pharyngeal orifice of the eustachian tube., Results: The drainage/ventilation route between the nasopharynx and middle ear cavity involving the cholesterol granuloma has been preserved more than for 9 months postoperatively. Her hearing has recovered., Conclusions: This less invasive technique is a surgical option for patients with a large cholesterol granuloma in the petrous apex involving the eustachian tube.

We examined the effect of the cytosolic Ca(2+) concentration ([Ca(2+)](c)) in marginal cells on the asphyxia- or furosemide-induced decrease in the endocochlear potential (EP) by perfusing the endolymph with or without a Ca(2+) chelator or inhibitors of Ca(2+)-permeable channels or Ca(2+)-pump during transient asphyxia or intravenous administration of furosemide. We obtained the following results. (1) Endolymphatic administration of SKF96365 (an inhibitor of TRPC and L-type Ca(2+) channels) or EGTA-acetoxymethyl ester (EGTA-AM) significantly inhibited both the transient asphyxia-induced decrease in EP (TAID) and the furosemide-induced decrease in EP (FUID). (2) Endolymphatic perfusion with nifedipine significantly inhibited the TAID but not the FUID. (3) The recovery from the FUID was significantly suppressed by perfusing the endolymph with EGTA-AM, nifedipine, or SKF96365. (4) Endolymphatic administration of thapsigargin inhibited both the FUID and TAID. (5) The recovery rate from the FUID was much slower than that from the TAID, indicating that furosemide may inhibit the Ca(2+)-pump. (6) A strong reaction in immunohistochemical staining for TRPC channels was observed in the luminal and basolateral membranes of marginal cells. (7) A positive staining reaction for the gamma subunit of epithelial Na(+) channels was observed in the luminal and basolateral membranes of marginal cells. (8) Positive EP was diminished toward 0 mV by the endolymphatic perfusion with 10 muM amiloride or 10 muM phenamil. Taken together, these findings suggest that [Ca(2+)](c) regulated by endoplasmic Ca(2+)-pump and Ca(2+)-permeable channels in marginal cells may regulate the positive EP, which is partly produced by the diffusion potential of Na(+) across the basolateral membrane in marginal cells.

Objective: Parathyroidectomy (PTx) is sometimes performed to treat secondary hyperparathyroidism (2HPT) related to long-term dialysis. In this procedure, all four parathyroid glands should be resected. However, in patients with 2HPT, the four glands are not uniformly enlarged; therefore, preoperative diagnosis is difficult in comparison with primary hyperparathyroidism. We compared glands detected on preoperative ultrasonography (US) with those resected during PTx to examine the usefulness and limitations of US., Methods: The subjects were 44 patients with 2HPT who underwent PTx between December 2003 and November 2007. Surgery was indicated for patients meeting the following three conditions: a serum intact PTH (iPTH) level of 500 pg/ml or more; a maximum glandular volume of 500 mm3 or more; and increased bone metabolism. Before surgery, we detected the parathyroid glands using US, and three-dimensionally measured their sizes. PTx was performed based on US diagnosis, and resected glands were weighed., Results: Assuming that four parathyroid glands are present in each patient, the total number of glands in the 44 patients was 176. Of the 176 glands, 139 were detected on preoperative US. However, 27 could not be resected. Therefore, the detection rate on US was 63.6% (112/176). Of 37 glands that could not be detected on preoperative US, 30 were detected during surgery, and resected. There was a positive correlation between the glandular volume measured on US and isolated gland weight. However, there was no correlation between the preoperative serum iPTH level and the sum of the four isolated gland weights., Conclusion: On preoperative US, approximately 80% of the glands were detected. However, the misdiagnosis rate was approximately 20%. The rate of accurate diagnosis was 63.6%. Even when glands were misdiagnosed or could not be confirmed on preoperative US, approximately 80% of them could be detected and resected during surgery. It may be impossible to estimate the glandular volume based on the preoperative serum iPTH level.

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.

Objective: Canal wall down (CWD) tympanoplasty with soft-wall reconstruction (SWR) is a unique technique for cholesteatoma surgery. The external auditory canal shape after surgery-retracted like a radical mastoid cavity or preserved intact-depends on postoperative aeration in the mastoid cavity. However, the relationship between postoperative middle ear aeration and hearing outcome with this procedure is unknown. We characterized this relationship and propose an ideal state of middle ear aeration to obtain satisfactory postoperative hearing after CWD tympanoplasty with SWR., Study Design: Retrospective case series., Patients: Seventy-eight patients (78 ears) with fresh cholesteatomas treated surgically at our hospital by planned 2-stage CWD tympanoplasty and SWR were included., Main Outcome Measures: Postoperative middle ear aeration was scored 1 year after second-stage surgery by computed tomography. The patients were divided into 4 bins according to postoperative audiometric air-bone (A-B) gaps: 0-10, 11-20, 21-30, and greater than 30 dB., Results: Postoperative middle ear aeration was significantly greater in the smaller gap bins (0-10 and 11-20 dB) compared with the larger A-B gap bins (21-30 and >30 dB). In contrast to the larger A-B gap bins, those with smaller A-B gaps showed reaeration of the antrum and mastoid cavity. No significant differences were observed in postoperative middle ear aeration or hearing outcome between the 2 cholesteatoma types., Conclusion: Promoting postoperative aeration of the entire middle ear is necessary to achieve better hearing outcome in patients undergoing CWD tympanoplasty and SWR for cholesteatoma.

Background: We describe the first case of extensive squamous cell carcinoma in the temporal bone recurring after surgery, conventional radiotherapy, and chemotherapy, which was treated using planned fractionated boron neutron capture therapy (BNCT)., Methods: A 42-year-old patient received BNCT twice with a 1-month interval to ensure neutron capture in the deep lesion. We used an epithermal neutron beam as the neutron source and boronophenylalanine as the boron compound. The total radiation doses in the tumor beneath the skin, at the deepest point of the tumor, and in the skin around the right auricle were estimated as 41.8, 36.9, and 15.8 Gy-Eq, respectively., Results: Radiological studies performed 6 months after the first BNCT showed obvious tumor shrinkage and no evidence of residual tumor., Conclusion: We believe that planned fractionated BNCT is an effective treatment option for patients with inoperative extended carcinomas in the temporal bone.

It was recently reported by us that either primary i.n. or i.p. injection of cedar pollen extract into BALB/c mice, or a second s.c. injection of the allergen into i.v. or s.c. sensitized mice, causes an IL-4-dependent increase in total IgE serum antibody to produce allergen-specific IgE antibody upon further s.c. sensitization. To determine the biology of total IgE antibody, in the present study IgE+ cells in peripheral blood or lymphoid tissues of allergen-sensitized BALB/c mice have been characterized. In peripheral blood, mice sensitized one to three times with the allergen produced a 2.5- to 4-fold increase in the number of IgE+ cells, with a time-course similar to that of the concentration of total IgE antibody in serum. These IgE+ cells were basophils. On the other hand, the number of IgE+ cells in the lymphoid tissues did not change significantly after an i.n., i.p., i.v. or s.c. injection of allergen into the mice, whereas a second s.c. injection of the allergen into the i.v.-, but not into the i.n.-, i.p.- or s.c.-, sensitized mice induced a small number of IgE+/IgM+/B220+ B cells in the spleen. In contrast, IgE+ cells were not seen in the blood or spleen of IL-4 -/- mice after sensitization with the allergen. These results suggest that IgE+ basophils in the peripheral blood, and IgE+ B cells in the spleen, might be IL-4-dependently induced as an indicator of sensitization with allergen, and a precursor of cells secreting allergen-specific IgE antibody, respectively.

Background: As a non-injection route for immunotherapy, local nasal immunotherapy has been examined in allergic rhinitis patients. However, it is unclear how the immunotherapy affects sneezing, biphasic nasal blockage and nasal hyperresponsiveness. Thus, we evaluated the therapeutic effects of nasal immunotherapy on the symptoms of guinea pig allergic rhinitis. Additionally, we also evaluated whether the immunotherapy relieved pollen-induced allergic conjunctivitis., Methods: Sensitized animals were repeatedly challenged by pollen inhalation once every week. After the 7th challenge, the pollen extract was intranasally administered 6 times a week until the 30th challenge. Sneezing frequency was counted after each of the challenges. As an indicator of nasal blockage, changes in specific airway resistance were measured. Nasal hyperresponsiveness was assessed by measuring leukotriene D(4)-induced nasal blockage. Additionally, during the immunotherapy, we applied pollen onto the ocular surface to induce the allergic conjunctivitis symptoms., Results: At the 11th-30th challenges, the nasal immunotherapy showed inhibition or a tendency to inhibit the biphasic nasal blockage although the inhibitions were variable at respective challenges. The development of nasal hyperresponsiveness was markedly suppressed by the immunotherapy. Nevertheless, neither sneezing nor antigen-specific IgE antibody production was substantially influenced by the immunotherapy. On the other hand, the nasal immunotherapy did not affect the induction of allergic conjunctivitis symptoms., Conclusions: Local nasal immunotherapy may be clinically useful for allergic nasal blockage associated with nasal hyperresponsiveness. The mechanisms responsible for this effectiveness might not be related to IgE production. Additionally, the effectiveness for nasal tissue was dissociated from that seen for the ocular tissue.

Synovial sarcomas account for 5% of pediatric soft tissue sarcomas, and primarily arise in the extremities. We report a case of synovial sarcoma in the parotid region. A 29-year-old woman presented with a 3-year history of a slow-growing, slight painful swelling in the preauricular region. The patient underwent right deep parotidectomy preserved with facial nerve. In immunohistochemistry, the epithelial cells were positive for cytokeratin AE1/3 and epithelial membrane antigen. The stromal cells were immunoreactive for vimentin and BCL2. The both types of cells were positive for CD99. The SYT-SSX fusion gene from chromosomal translocation was detected by fluorescence in situ hybridization in this case.

Objectives: We compared the use of the pedicled temporoparietal fascial flap (TPFF) with the use of free deep temporal fascia (DTF) in soft-wall reconstruction after canal wall-down tympanoplasty., Methods: In the TPFF group (6 ears), the pedicled TPFF that includes the superficial temporal artery and vein was raised ipsilaterally and rotated into the eradicated mastoid cavity. The tympanic membrane and external auditory canal (EAC) were reconstructed by gluing one side of the TPFF to the mucosal layer of the tympanic membrane and the reverse side of the posterior EAC skin. In the DTF group (21 ears), reconstruction was performed similarly with free DTF. The postoperative period for epithelialization of the tympanic membrane and EAC skin, postoperative complications, and reaeration in the middle ear revealed by computed tomography were reviewed in both groups., Results: In the TPFF group, the mean (+/- SD) period to epithelialization was 25.5 +/- 2.8 days versus 38.4 +/- 12.0 days in the DTF group; the two groups differed statistically (Welch's t-test, p = 0.0002). No postoperative complications occurred in the TPFF group, whereas 2 patients in the DTF group underwent graft necrosis with infection. Three of the 6 patients in the TPFF group showed reaeration not only in the tympanic cavity, but also in the mastoid cavity. However, no statistical differences between the two groups were observed in terms of postoperative complications or reaeration of the mastoid cavity., Conclusions: Our preliminary findings suggest that the pedicled TPFF has positive effects on quick epithelialization. Further prospective studies are needed to reveal the superiority of the pedicled TPFF over free DTF with regard to postoperative infection and recovery of mastoid aeration.

Objective: To compare the incidence and localization of residual cholesteatomas in canal wall down tympanoplasty with soft-wall reconstruction with results with the canal wall down and open tympanoplasty or canal wall up tympanoplasty., Design: Retrospective case-series study., Setting: Tertiary care university hospital., Patients: Eighty-five patients (85 ears) with fresh extensive cholesteatomas who underwent canal wall down tympanoplasty with soft-wall reconstruction as first-stage surgery and a second operation after 1 year to confirm residual cholesteatomas and perform ossiculoplasty., Main Outcome Measures: The incidence and localization of residual cholesteatomas in the middle ear were compared between surgery using the canal wall down and open tympanoplasty and canal wall up tympanoplasty. Possible technical causes of the residua were reviewed in a retrospective videotape analysis of the first-stage operations., Results: Of the 85 ears operated on, 18 had residual cholesteatomas, for an overall incidence of 21%, with 1 residuum per ear. Six cholesteatomas were located in the epitympanum (33%), 3 in the sinus tympani (17%), 3 in the antrum (17%), 2 on the stapes (11%), 2 on the tympanic membrane (11%), 1 on the tympanic portion of the facial canal (6%), and 1 just under the skin of the external auditory canal (6%). The retrospective videotape analysis revealed that the main cause of residual cholesteatomas in the epitympanum and sinus tympani was incomplete removal of the matrix under an indirect surgical view because of insufficient drilling. Residual matrix in a bony defect in the middle cranial fossa or facial canal was the cause of residual cholesteatomas in the antrum or facial canal. Inappropriate keratinizing epithelium rolling during tympanic membrane or external auditory canal reconstruction was the cause of residual cholesteatomas in the tympanic membrane or external auditory canal., Conclusions: The incidence of residual cholesteatomas in patients who underwent canal wall down tympanoplasty with soft-wall reconstruction was similar to that in patients who underwent surgery involving the canal wall down and open tympanoplasty or canal wall up tympanoplasty. In terms of localization, with canal wall down tympanoplasty with soft-wall reconstruction, there is the possibility of residua not only in the tympanic cavity but also in the antrum or mastoid cavity, as with the canal wall up method. Results of this study suggest that in patients with extensive cholesteatoma, canal wall down tympanoplasty with soft-wall reconstruction should be followed by a second procedure to detect any residual cholesteatomas in the tympanic cavity, antrum, or mastoid cavity.

We recently reported a system for inactivating antineoplastics in which sodium hypochlorite is supplied by the electrolysis of sodium chloride solution. In this study, we designed an electrolysis apparatus for inactivating the cytotoxicity of antineoplastics in clinical wastewater using the system. The apparatus consists of an electrolysis cell with platinum-iridium electrodes, a pool tank, a circulating system for wastewater, a safety system for explosive gas and overflow, and an exhaust duct. The free chlorine concentration increased linearly up to 6500 mg l(-1), and pH also increased to 9.0-10.0 within 2h, when 0.9% sodium chloride solution was electrolyzed. We examined its efficacy with model and clinical wastewaters. The reciprocal of dilution factor for disappearance of cytotoxicity using Molt-4 cells was compared before and after electrolysis. In the model wastewater, that was 9.10 x 10(4) before electrolysis, and 3.56 x 10(2) after 2h of electrolysis. In the clinical wastewater (n=26), that was 6.90 x 10(3)-1.02 x 10(6) before electrolysis, and 1.08 x 10(2)-1.45 x 10(4) after 2h of electrolysis. Poisonous and explosive gases released by the electrolysis were measured; however, they were found to be negligible in terms of safety. The environmental load was evaluated by carbon dioxide generation as an index and it was found that the carbon dioxide generated by the electrolysis method was 1/70 lower than that by the dilution method with tap water. Moreover, the cost of the electrolysis method was 1/170 lower than that of the dilution method. This method was found to be both effective and economically valuable.

To establish a simple, reproducible procedure for studying facial motor nerve conduction (MNC), we determined the optimal electrode position to record evoked compound muscle action potentials (CMAPs) from perioral muscles in normal subjects. We examined three new electrode positions in which the electrode connected to the one input of the amplifier was placed on the mental protuberance, and the one connected to the other input was placed on the skin over the orbicularis oris muscle (the philtrum, mouth angle, or lower lip). We then compared the morphology and amplitudes of the CMAPs, right-left differences, and the reproducibility of CMAP amplitudes with recordings taken from the standard electrode position in which one electrode was placed on the nasolabial fold closely lateral to the ala nasi, and the other was placed on the skin over the orbicularis oris. Percutaneous supramaximal electrical stimulation was applied to the main trunk of the facial nerve. All three of the new recording positions showed greater amplitudes and more obvious biphasic CMAPs than the standard method. Positioning the electrode connected to the negative input on the philtrum was optimal in terms of right-left differences and the reproducibility of CMAP amplitudes. Therefore, this midline recording is a simple, reproducible method for calculating the CMAP amplitude ratio. However, prior to clinical use of this procedure, analyses of patients with facial palsy are required.

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.

The apoptosis of bone marrow-derived mast-cells (BMMCs) after growth factor withdrawal was significantly prevented by a high concentration of IgE in the absence of antigen, and further enhanced by the presence of Toll-like receptor4 (TLR4) ligand, lipopolysaccharide (LPS). The effect of LPS was mediated by TLR4, since TLR4-deficient BMMCs did not show synergistic effects with IgE. The neutralizing amount of anti-IL-3 did not reverse the anti-apoptotic effects of both IgE and combination with LPS. LPS treatment with monomeric IgE synergistically prevented the loss of mitochondrial membrane potentials and was associated with an enhanced expression of anti-apoptotic protein, Bcl-xL, or with a reduced expression of proapoptotic protein, Puma, and Bim, respectively. Altogether, these results suggest that LPS, in a TLR4-dependent manner, together with IgE, synergistically prevent mast-cell apoptosis and may contribute to regulate the tissue mast-cell number.

To explore which cytokine or cell is essential for the production of antibodies (Abs) of the IgE class in allergic diseases, we injected cedar pollen into wild-type, interferon-gamma(-/-) (IFN-gamma(/)), or interleukin-4(-/-) (IL-4(-/-)) BALB/c mice through four (i.n., i.p., s.c., and i.v.) different routes without adjuvant. Wild-type or IFN-gamma(-/-), but not IL-4(-/-), mice sensitized once or twice showed a significant increase in total IgE Ab in their serum, revealing the essential role of IL-4 in the production of total IgE Ab. We separated peripheral blood mononuclear cells (PBMCs) from untreated or sensitized mice into monocyte-rich, lymphocyte-rich, and granulocyterich populations by Percoll density-gradient centrifugation or into specific antigen cells by flow cytometry, cultured the cells in various combinations, and examined the levels of cytokines and IgE Ab released into the medium. The PBMCs from mice sensitized s.c. once, but not those from untreated animals, produced significant amounts of IL-4 and total IgE Ab, whereas the lymphocyte-rich population alone did not. Unexpectedly, IL-4 and IgE Ab production was restored by the addition of Mac-1(+) cells in the monocyte-rich fraction to the lymphocyte-rich fraction. These results indicate the essential role of monocytes in the production of IL-4 and total IgE Ab by lymphocytes during the initial stage of sensitization.

To elucidate the mechanisms underlying nasal symptoms in patients with aspirin hypersensitivity, we evaluated the effects of orally administered non-steroidal anti-inflammatory drugs (NSAIDs) on the nasal patency of guinea pigs with cedar pollen-induced chronic allergic rhinitis. Indomethacin (10 mg/kg) administered 1 h before a pollen challenge amplified the antigen-induced nasal blockage. More interestingly, even in the absence of the pollen challenge, indomethacin induced nasal blockage at 30 min at 4 h after administration. However, indomethacin-induced nasal blockage was not provoked in non-sensitized animals. Another NSAID, diclofenac (30 mg/kg), also evoked nasal blockage, but unexpectedly, aspirin (500 mg/kg) did not affect nasal patency. Indomethacin-induced nasal blockage was unaffected by a cysteinyl leukotriene receptor (CysLT(1) receptor) antagonist, pranlukast (30 mg/kg, p.o.), or by prostaglandin E2 (10(-3) M, intranasal), suggesting that the nasal blockage may not be due to hyperproduction of cysteinyl leukotrienes or inhibition of prostaglandin E2 production. These results indicate that the indomethacin-induced nasal blockage may not be an identical phenomena to airway symptoms in aspirin hypersensitivity patients. However, because chronic nasal inflammation is indispensable for the development of nasal blockage, indomethacin-induced nasal blockage may become a clue to elucidate new mechanisms underlying hypersensitivity to NSAIDs.

Using immunohistochemical and electrophysiological methods, we investigated the role of L-type Ca(2+) channels in the regulation of the endocochlear potential (EP) of the endolymphatic surface cells (ESC) of the guinea pig stria vascularis. The following findings were made: (1) Administration of 30 microg/ml nifedipine via a vertebral artery significantly suppressed the transient asphyxia-induced decrease in the EP (TAID) and the transient asphyxia-induced increase in the Ca(2+), referred to as TAIICa, concentration in the endolymph ([Ca](e)). (2) The endolymphatic administration of 1 microg/ml nifedipine significantly inhibited the TAID as well as the TAIICa. The endolymphatic administration of nifedipine (0.001-10 microg/ml) inhibited the TAID in a dose-dependent manner. (3) The endolymphatic administration of (+)-Bay K8644, an L-type Ca(2+) channel closer, significantly inhibited the TAID, whereas (-)-Bay K8644, an L-type Ca(2+) channel opener, caused a large decrease in the EP from approximately +75 mV to approximately +20 mV at 10 min after the endolymphatic administration. (4) By means of immunohistochemistry, a positive staining reaction with L-type Ca(2+) channels was detected in the marginal cells of the stria vascularis. (5) Under the high [Ca](e) condition, we examined the mechanism of the TAIICa and hypothesized that the TAIICa might have been caused by the decrease in the EP through a shunt pathway in the ESC. (6) The administration of nifedipine to the endolymph significantly inhibited the Ba(2+)-induced decrease in the EP. These findings support the view that L-type Ca(2+) channels in the marginal cells regulate the EP, but not directly the TAIICa.