記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMED CENTRAL LTD  

Background: Regenerating gene (REG) family is composed of antiapoptotic factors and growth factors that affect epithelial cells within the digestive system. Regenerating gene-I has been studied in different cancers. However, it has never been studied in head and neck cancer. We investigated the expression of REG-I in head and neck SCC and its relevance to patient survival rates.
Methods: Untreated biopsy specimens of 60 patients with stage IV head and neck SCC were collected, and the expression of REG-I was evaluated using immunohistochemistry. The association between REG-I expression and clinico-pathological features or survival status of the patients was assessed by Chi-square test, Fisher's exact test and Kaplan-Meier method. Cox proportional hazard model was used to identify the independent prognostic factors.
Results: Incidence of lymphatic permeation, vascular invasion and pathological lymph nodes was significantly higher in REG-I negative group (p = 0.008, 0.030 and 0.015, respectively). Overall and cancer-free survival rates were significantly higher in REG-I positive group (p = 0.000434 and 1.0847E-8, respectively). Univariate analysis showed that REG-I was an independent prognostic factor for predicting long-term overall survival (p = 0.002), and multivariate analysis showed that REG-I and lymphatic permeation were independent prognostic factors for predicting long-term disease-free survival (p = 0.001 and 0.022, respectively).
Conclusion: Our results showed for the first time that, REG-I is expressed in head and neck SCC. REG-I expression is associated with a longer survival status. We conclude that, REG-I might be a prognostic marker in head and neck SSC and should be further investigated.

DOI： 10.1186/s13000-016-0526-y

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記述言語：英語   出版者・発行元：CURRENT MEDICINE GROUP  

The traditional paradigm of eosinophils as endstage damaging cells has mainly relied on their release of cytotoxic proteins. Cytokine-induced cell survival and secretion of granular contents from tissue-dwelling eosinophil are thought to be important mechanisms for eosinophilic inflammatory disorders, although the occurrence of cytolysis and its products (i.e., free extracellular granules) has been observed in affected lesions. Recent evidence indicates that activated eosinophils can exhibit a non-apoptotic cell death pathway, namely extracellular trap cell death (ETosis) that mediates the eosinophil cytolytic degranulation. Here, we discuss the current concept of eosinophil ETosis which provides a new look at eosinophilic inflammation. Lessons from eosinophilic chronic rhinosinusitis revealed that ETosis-derived DNA traps, composed of stable web-like chromatin, contribute to the properties of highly viscous eosinophilic mucin and impairments in its clearance. Intact granules entrapped in DNA traps are causing long-lasting inflammation but also might have immunoregulatory roles. Eosinophils possess a way to have post-postmortem impacts on innate immunity, local immune response, sterile inflammation, and tissue damage.

DOI： 10.1007/s11882-016-0634-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPANESE SOCIETY ALLERGOLOGY  

Background: The chemokine receptor, CC-chemokine receptor 3 (CCR3), and its major ligands, eotaxin, RANTES, and MCP-4, are involved in eosinophil chemotaxis. It is thought that CCR3 plays an important role in the recruitment and activation of eosinophils in nasal polyposis. We examined nasal polyp extract-induced eosinophil chemotaxis and the effect of a CCR3 antagonist using EZ-TAXIScan, a novel real-time chemotaxis assay device.
Methods: Nasal polyps were obtained from chronic rhinosinusitis (CRS) patients during surgery. The polyps were homogenized and eotaxin levels in the extracts were measured. Eosinophils were purified from human peripheral blood by the CD16 negative selection method. Nasal polyp extract-induced eosinophil chemotaxis, with or without CCR3 antagonist, was assessed by EZ-TAXIScan.
Results: There was a significant positive correlation between the eosinophil counts in nasal polyp and eotaxin levels in the nasal polyp extracts. Using EZ-TAXIScan, eosinophil chemotactic responses were observed following stimulation with nasal polyp extracts. There was a significant positive correlation between the chemotactic index toward the nasal polyp extracts and their eotaxin levels. Nasal polyp extract-induced chemotaxis was completely inhibited by CCR3 antagonist but not by chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) antagonist which inhibited PGD(2)-induced eosinophil chemotaxis.
Conclusions: The CCR3 pathway may play an important role in the pathogenesis of eosinophil recruitment in nasal polyps through selective eosinophil chemotaxis. Copyright (C) 2016, Japanese Society of Allergology. Production and hosting by Elsevier B.V.

DOI： 10.1016/j.alit.2016.01.001

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI LTD  

Objective: Sublingual immunotherapy (SLIT) appears to offer practical advantages for the treatment of allergic rhinitis (AR). Based on a review of the scientific literature, we present recommendations as guiding principles to administer SLIT safely.
Methods: Clinical questions concerning SLIT were prepared. Literature published between January 2003 and December 2012 was searched from PubMed, the Cochrane Library, and Japana Centra Revuo Medicina. Qualified studies were analyzed and the results were evaluated, consolidated, and codified. We answered 17 clinical questions and, based on this, presented evidence-based recommendations.
Results: Sublingual immunotherapy improved symptoms (e.g., quality of life [QOL]) and reduced medication scores in seasonal AR and perennial AR. Most SLIT-induced adverse effects were local oral reactions, although systemic adverse effects such as gastrointestinal symptoms, urticaria, and asthma are occasionally reported. There have been no reports of lethal anaphylactic reactions by SLIT. When SLIT is continued for 3-4 years, its effect persists long after discontinuation.
Conclusion: A correct diagnosis of AR and sufficient informed consent from patients are required before initiating SLIT. Sublingual immunotherapy should be continued for 3 years or longer. The initial administration of SLIT during the uptitration of an allergen vaccine and the general condition of patients are critical for the safe performance of SLIT. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.anl.2015.08.015

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MOSBY-ELSEVIER  

Background: Activated human eosinophils, as well as neutrophils, can release extracellular chromatin to form DNA traps through cytolytic extracellular trap cell death (ETosis). Although formations of neutrophil DNA traps are recognized in patients with various inflammatory conditions, neither the presence of ETosis-derived eosinophil DNA traps in human allergic diseases nor the characteristics of these DNA traps have been studied.
Objective: We investigated the presence of ETosis-derived DNA traps in eosinophil-rich sinus and ear secretions and the functional attributes of ETosis DNA traps.
Methods: Eosinophil-rich secretions obtained from patients with eosinophilic chronic rhinosinusitis and eosinophilic otitis media were studied microscopically. In vitro studies of ETosis and DNA trap formation used blood-derived eosinophils and neutrophils, and studies of the binding capacities of DNA traps used labeled bacteria and fluorescent microbeads. Stabilities of DNA traps were evaluated by using fluorescence microscopy. Results: Abundant nuclear histone H1-bearing DNA traps formed in vivo in the eosinophilic secretions and contributed to their increased viscosity. In vitro, after brief shear flow, eosinophil ETosis-elicited DNA traps assembled to form stable aggregates. Eosinophil DNA traps entrapped bacteria and fungi and, through hydrophobic interactions, microbeads. In comparison with neutrophil-derived DNA traps, eosinophil DNA traps ultrastructurally exhibited thicker fibers with globular structures and were less susceptible to leukocyte-derived proteolytic degradation, likely because of the lesser protease activities of eosinophils.
Conclusions: In human allergic diseases local cytolysis of eosinophils not only releases free eosinophil granules but also generates nuclear-derived DNA traps that are major extracellular structural components within eosinophil-rich secretions.

DOI： 10.1016/j.jaci.2015.04.041

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MANEY PUBLISHING  

S-1 granulated powder has recently been released to the market as an additional format to that of the capsule. Patients who previously found it difficult to swallow the capsules are now able to take S-1 in powder form. This study evaluated the feasibility of S-1 granulated powder as adjuvant chemotherapy for advanced head and neck cancer. S-1 was orally administered for 2 weeks, followed by 1 week of rest (one course) for 12 months (16 courses). Twenty-four stage III and IV head and neck cancer patients were enrolled in this study. In total, 10 (47.6%) of the patients follow the planned schedule and dose. Severe adverse events were observed in 22 patients (91.7%), whereas no grade 4 adverse events were observed. S-1 granulated powder should be presented as an additional option for the treatment of head and neck cancer, especially for patients experiencing difficulty in swallowing oral medications.

DOI： 10.1179/1973947815Y.0000000014

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：INFORMA HEALTHCARE  

Conclusions: Because computed tomography (CT) lymphography provides preoperative images of anatomic relationships between a tumor, its associated lymph vessels, and the sentinel lymph node (SLN), it may aid in directing the SLN biopsy for management of early tongue cancer. Objectives: SLN biopsy using a radioisotope (RI) generally has been performed in head and neck cancer. However, this method can be performed only at institutions that are licenced for its use. In this study, we evaluated the utility of performing SLN biopsy in patients with early tongue cancer using the newly developed technique of CT lymphography. Methods: Enrolled in this study were 31 patients with T1N0 or T2N0 tongue cancer. CT images were obtained before and after injection of iopamidol into the peritumoral region and the SLN was identified as the first enhanced lymph node. SLN biopsy was performed using CT lymphographic guidance combined with blue dye injection. Results: The SLN was detected by CT lymphography in 28 cases (90.3%). By intraoperative frozen section examination, metastases to SLNs were found in 4 (14.3%) (T1N0, 1 patient; T2N0, 3 patients) of the 28 patients. Of these four, SLN micrometastases were found in one patient.

DOI： 10.3109/00016489.2015.1010126

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI LTD  

The patient is a 64-year-old woman who developed a sensation of right ear fullness and hearing loss in early November 2010. Physical examination revealed a painless reddish granular lesion filling in the right external auditory canal. Her right ear was deaf, and no facial palsy was noted. Computed tomography, magnetic resonance imaging and positron emission tomography revealed a middle ear mass extending to the external auditory canal with intracranial invasion causing temporal lobe retraction and inferiorly extending just anterior to the jugular bulb as well. A combination of transmastoid and middle cranial fossa approach along with anterior rerouting of the facial nerve was employed for a near-total removal of the tumor. Based upon the operative findings, it was deemed that the tumor could have arisen from the Jacobson's nerve. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.anl.2014.05.005

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記述言語：英語  

DOI： 10.1055/s-0034-1376428

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI LTD  

Objective: Hearing screening programs in schools are particularly important for children because they can enable early detection of hearing problems and early intervention. However, there has been little research on this topic. The MB11BERAphone(R) is a novel, accurate and efficient Automated Auditory Brainstem Response device for hearing screening in infants. The aim of this study was to investigate the validity of the MB11BERAphone(R) as a hearing screening device for pre-school, school-age and young-adult individuals.
Methods: Between January 2010 and March 2012, 163 normal and hearing impaired individuals, corresponding to 321 ears from subjects aged 3-22 years 11 months at Luther Aiji Kindergarten and Nakadori General Hospital in Akita, Japan, underwent primarily conditional play audiometry or conventional audiometry followed by the Automated Auditory Brainstem Response by MB11BERAphone(R). The statistical analysis was performed with the Predictive Analytics Software (PASW Statistics 18) and presented as the mean, standard deviation (SD) and frequency distribution. The sensitivity, specificity and false-positive and false-negative rates were estimated to analyze the validity of the MB11BERAphone(R) test over audiometry.
Results: Among the normal and hearing impaired ears, 140 were scored as "REFER" and 181 were scored as "PASS" during the hearing screening examination conducted using the MB11BERAphone(R) device. The specificity was 95.1%, and the sensitivity was 96.3%. The false positive rate was 5%, and the false negative rate was 4%. The overall timing without precise measurement was less than 7 min. The individuals were divided into groups: pre-schoolers (3-5 years), school-age (6-17 years) and young-adults (18-22 years). When the audiometry and MB11BERAphone(R) results were compared, no statistically significant differences (p = ns) were detected among general (pre-schoolers + school-age + young-adult), preschool, school-age, and young-adult groups.
Conclusion: The results suggest that the MB11BERAphone(R) is not only useful for newborn hearing screening but also for hearing screening in older individuals, due to the low cost of the integrated electrodes and the speed with which the examination can be performed. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.anl.2013.08.001

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI LTD  

Objective: In anticipation of the development of guidelines for antigen-specific subcutaneous immunotherapy (SCIT), we present recommendations that can serve as guiding principles based on a review of the scientific literature.
Methods: Clinical questions (CQs) concerning SCIT were prepared. Literature searches for publications between January 1990 and February 2011 were performed in PubMed, the Cochrane Library, and Japana Centra Revuo Medicina Web version 4. Qualified studies were analyzed and the results were evaluated, consolidated, and codified.
Results: We present answers for 13 CQs on the indications, methods, effectiveness and mechanisms of SCIT, with evidence-based recommendations.
Conclusion: The guiding principles are intended to be applied to children (<= 15 years old) and adults (>= 16 years old) with allergic rhinitis (AR). These principles can be used by otorhinolaryngologists for diagnosis of AR, evaluation of severity and rhinoscopic findings, performance of antigen challenge tests, and management of systemic anaphylactic reactions associated with SCIT. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.anl.2013.06.003

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPANESE SOCIETY ALLERGOLOGY  

Background: The prevalence of Japanese cedar (JC) pollinosis in Japanese children is increasing. However, few studies have reported the relationship between pollen count levels and the prevalence of pollinosis. To evaluate the relationship between JC pollen count levels and the prevalence of pollinosis in children, we investigated the sensitization and development of symptoms for JC pollen in two areas of Akita in northeast Japan with contrasting levels of exposure to JC pollen.
Methods: The study population consisted of 339 elementary school students (10-11 years of age) from the coastal and mountainous areas of Akita in 2005-2006. A questionnaire about symptoms of allergic rhinitis was filled out by the students' parents. A blood sample was taken to determine specific IgE antibodies against five common aeroallergens.
Results: The mean pollen count in the mountainous areas was two times higher than that in the coastal areas in 1996-2006. The prevalence rates of nasal allergy symptoms and sensitization for mites were almost the same in both areas. On the other hand, the rates of nasal allergy symptoms and sensitization for JC pollen were significantly higher in the mountainous areas than in the coastal areas. The rate of the development of symptoms among children sensitized for JC pollen was almost the same in both areas.
Conclusions: These results suggest that pollen count levels may correlate with the rate of sensitization for JC pollinosis, but may not affect the rate of onset among sensitized children in northeast Japan.

DOI： 10.2332/allergolint.12-OA-0526

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記述言語：日本語   出版者・発行元：一般社団法人 日本耳鼻咽喉科学会  

重心動揺の測定は, 平衡機能や姿勢制御機能を評価する方法として従来から日常臨床の場で広く実施されてきた. しかし高齢者にみられるような加齢に伴う平衡障害など, このような検査では評価が困難な例も多い. また姿勢制御の本質的な評価には, 重心動揺だけでなく頭部動揺も含めた全身的な解析が重要であるといわれてきたが, これらを正確にかつ簡便に計測する方法は少ない. 本研究では, 磁気式モーションキャプチャーシステムを用いて直立時の頭部と体幹の動きを記録し, 加齢による変化を観察するとともに本システムの有用性を検討した. 66歳から83歳までの高齢者7名を対象に, 重心動揺計の上に開眼と閉眼でそれぞれ30秒間の両脚起立を行い, 頭部, 頸部, 腰部の動揺を三次元的に記録し, 重心の動揺と比較した. その結果, 直立時の身体動揺は頭部が最も大きく, 次が頸部, 腰部の順であった. また腰部動揺の軌跡は重心動揺の軌跡とよく一致していた. これら身体動揺は年齢に伴って大きくなり, ふらつきを訴える患者でより大きな動揺が観察された. 腰部動揺に対する頭部動揺の比率も年齢とともに大きくなり, 姿勢制御機能を評価するための有効な指標となると思われた. 磁気式モーションキャプチャーシステムは, 正確かつ簡便なため日常診療の検査にも応用可能で, これを用いて身体の動揺を計測することにより, 従来の検査でははっきりしない潜在的な異常も検出できる可能性が示唆された.

DOI： 10.3950/jibiinkoka.116.1106

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1159/000327294

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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

DOI： 10.2332/allergolint.08-OA-0004

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Society of Allergology  

Background: Peroxisome proliferator-activated receptor γ (PPAR-γ) has been shown to play an important role in the control of inflammatory responses acting on macrophages, mast cells, T cells, and eosinophils. The present study was aimed at investigating the effects of PPAR-γ agonist on nasal symptoms and eosinophil accumulations in nasal mucosa by using a murine allergic rhinitis model. Furthermore, we examined the expression of PPAR-γ in the nasal mucosa in mice. Methods: BALBac mice were sensitized and challenged intranasally with ovalbumin. Ciglitazone, a PPAR-γ agonist, was administered orally 6 hours before each nasal challenge. Results: Administration of PPAR-γ agonist significantly decreased the number of nasal rubs, nasal histamine responsiveness, serum IgE, IL-5 production from the spleen, and eosinophilic infiltration in the nasal mucosa. Furthermore, PPAR-γ was expressed in eosinophils and epithelial cells in the nasal mucosa by immunohistochemistry. Conclusions: PPAR-γ was expressed in eosinophils and epithelial cells in the nasal mucosa. Also, the oral administration of ciglitazone is effective in upper airway allergic inflammation in mice. © 2009 Japanese Society of Allergology.

DOI： 10.2332/allergolint.08-OA-0047

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：W B SAUNDERS CO-ELSEVIER INC  

Giant cell tumor is a bony tumor which primarily occurs in third to fourth decade after skeletal maturation. Usually, this tumor arises in the distal end of long bone and is quite rare in the head and neck region. We had a elderly female patient with giant cell tumor at lateral skull base of the left temporal bone without classic symptoms. Team approach with neurosurgeon was used to eradicate the tumor. The detail of this case in conjunction with treatment of giant cell tumor was reported while reviewing pertinent papers. (c) 2006 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.amjoto.2005.05.021

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MOSBY, INC  

Background: Allergic asthma is associated with persistent functional and structural changes in the airways and involves many different cell types. Peroxisome proliferator-activated receptor gamma (PPAR-gamma), a member of the nuclear hormone receptor superfamilly, is predominantly expressed in adipose tissue and plays a major role in regulating adipocyte differentiation and glucose metabolism. Recently, PPAR-gamma has been shown to play an important role in the control of inflammatory responses, including within the lung, acting on both immune and nonimmune cells.
Objective: Our aim was to assess the anti-inflammatory potential of a PPAR-gamma agonist locally delivered by means of nebulization.
Methods: We used a mouse model of asthma induced by sensitization and airway challenge with ovalbumin. Ciglitazone, a PPAR-gamma agonist, was administered by means of nebulization alone at the time of antigen challenge or by means of gavage and nebulization. Treatments with both ciglitazone and GW9662, a specific antagonist, were also performed to verify that ciglitazone's effects were mediated through PPAR-gamma activation.
Results: Our results show that PPAR-gamma is mainly expressed in airway epithelium on antigen sensitization. Treatment with ciglitazone reduced PPAR-gamma levels in the lung, whereas combined treatment with GW9662 abrogated this inhibition. Importantly, nebulization with ciglitazone decreased airway hyperresponsiveness, basement membrane thickness, mucus production, collagen deposition, and TGF-beta synthesis. A significant correlation was also found between airway hyperresponsiveness, basement membrane thickness, and TGF-beta levels.
Conclusion: These results demonstrate that inhaled agonistic ligands of PPAR-gamma might have new therapeutic potential for airway asthmatic inflammation.

DOI： 10.1016/j.jaci.2004.02.036

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ROCKEFELLER UNIV PRESS  

Allergic asthma is characterized by airway hyperresponsiveness, eosinophilia, and mucus accumulation and is associated with increased IgE concentrations. We demonstrate here that peroxisome proliferator-activated receptors (PPARs), PPAK-alpha and PPAR-gamma, which have been shown recently to be involved in the regulation of various cell types within the immune system, decrease antigen-induced air-way hyperresponsiveness, lung inflammation, eosinophilia, cytokine production, and GATA-3 expression as well as serum levels of antigen-specific IgE in a murine model of human asthma. In addition, we demonstrate that PPAR-alpha and -gamma are expressed in eosinophils and their activation inhibits in vitro chemotaxis and antibody-dependent cellular cytotoxicity. Thus, PPAR-alpha and -gamma (co)agonists might be of therapeutic interest for the regulation of allergic or inflammatory reactions by targeting both regulatory and effector cells involved in the immune response.

DOI： 10.1084/jem.20021384

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI LTD  

Cases with maxillary cancer are most frequently found in the 5th to the 7th decades of life, and then rarely occur in adolescence, even less so in a children. One does not expect to encounter this tumor in children, considering that most have a non-epithelial origin. However, we had a case of maxillary squamous cell carcinoma which appeared in a 12-year-old boy. He was initially considered to have sinusitis. and received conservative treatment for a while. After diagnosis, a combination therapy consisting of preoperative irradiation along intra-arterial administration of 5-FU and CBDCA was followed by total maxillectomy and primary reconstruction, Unfortunately about 2 months later, distant metastasis developed along with local recurrence, and the boy died about 1 year 6 months after the initial presentation. The clinical details of this rare case will be discussed in conjunction with some important considerations in dealing with this type of malignancy in a child. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

DOI： 10.1016/S0385-8146(02)00109-8

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