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• Exhaled nitric oxide and inducible nitric oxide synthase gene polymorphism in Japanese asthmatics

  S. Sato, X. Wang, J. Saito, A. Fukuhara, M. Uematsu, Y. Suzuki, Y. Sato, K. Misa, T. Nikaido, N. Fukuhara, Y. Tanino, M. Munakata

  Allergology International (2016).

  
  

  Abstract

  Inducible nitric oxide synthase (iNOS) induced by inflammatory cytokines and iNOS activity in bronchial epithelial cells is a major determinant of fractional exhaled nitric oxide (FeNO) levels. The aim of this study was to investigate the association of iNOS promoter gene polymorphisms and FeNO levels in Japanese asthmatics before the introduction of asthma treatment. Asthmatics were recruited from Fukushima Medical University Hospital. Genotyping of the pentanucleotide repeat (CCTTT)n and seven previously detected single nucleotide polymorphisms (SNPs) in the iNOS promoter lesion was performed. The relationships between the genotypes and FeNO levels before the introduction of asthma treatment were compared. In 91 asthmatics, the number of microsatellite repeats ranged from 9 to 20 and showed a bimodal distribution. According to this distribution, asthmatics were divided into two groups: genotypes with at least one long allele with more than 14 repeats (L/s or L/L) and genotypes with both short alleles with 14 or fewer repeats (s/s). No significant differences were observed in each parameter between the two groups. The mean FeNO level before treatment was significantly higher in the L/s or L/L subjects than in the s/s subjects. After treatment, the lowest FeNO level did not differ between the two groups. Three SNPs detected in the Japanese subjects were not associated with FeNO levels. The number of CCTTT repeats in the iNOS promoter region was associated with FeNO levels in asthmatics before treatment, suggesting the importance of iNOS genotype in the clinical application of FeNO for asthmatics.

  Abstract
  Inducible nitric oxide synthase (iNOS) induced by inflammatory cytokines and iNOS activity in bronchial epithelial cells is a major determinant of fractional exhaled nitric [...]

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• Accidental usage of an adrenaline auto-injector in Japanese children with a food allergy

  K. Sasaki, T. Nakagawa, S. Sugiura, N. Kando, K. Ito

  Allergology International (2016).

  
  

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• Eosinophil chemotaxis assay in nasal polyps by using a novel optical device EZ-TAXIScan: Role of CC-chemokine receptor 3

  H. Saito, K. Honda, C. Asaka, S. Ueki, K. Ishikawa

  Allergology International (2016).

  
  

  Abstract

  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. 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. 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 PGD2-induced eosinophil chemotaxis. The CCR3 pathway may play an important role in the pathogenesis of eosinophil recruitment in nasal polyps through selective eosinophil chemotaxis.

  Abstract
  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 [...]

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• Effect of intranasal corticosteroid on pre-onset activation of eosinophils and mast cells in experimental Japanese cedar pollinosis

  Y. Noyama, M. Okano, T. Fujiwara, S. Kariya, S. Makihara, T. Haruna, K. Kanai, T. Higaki, K. Nishizaki

  Allergology International (2016).

  
  

  Abstract

  Minimal persistent inflammation (MPI) contributes to hyperreactivity in allergic rhinitis. However, little is known regarding whether pre-onset activation of eosinophils and mast cells is present or not in Japanese cedar pollinosis (JCP). Furthermore, a prophylactic effect of intranasal corticosteroids on such MPI in JCP has not been investigated. We designed a double-blinded, randomized, placebo-controlled, crossover trial. Twenty patients with JCP were examined outside the pollen season (UMIN000008410). Nasal provocation with paper discs containing extracts of Japanese cedar pollen was performed once a day for 3 consecutive days. Onset of nasal symptoms was monitored over 15 min after each provocation. The levels of eosinophil cationic protein (ECP) and tryptase in nasal secretions were examined. Fluticasone furoate nasal spray or placebo treatment was started one day before the first provocation. In the placebo group, 25% of the patients showed onset of nasal symptoms following provocation on the first day. In addition, 75% and 68% of the patients showed symptom onset on the second and third day of provocation, respectively. After the first provocation, the levels of ECP and tryptase in nasal secretions were significantly increased. These increases were seen not only in symptomatic but also in asymptomatic subjects in response to provocation, and the levels were similar between these subjects. Prophylactic treatment with fluticasone significantly suppressed the increase in nasal ECP and tryptase associated with repeated provocations. These results suggest that pre-onset activation of eosinophils and mast cells is present in experimental JCP, and that prophylactic treatment with intranasal corticosteroids has the potential to control such activation.

  Abstract
  Minimal persistent inflammation (MPI) contributes to hyperreactivity in allergic rhinitis. However, little is known regarding whether pre-onset activation of eosinophils and [...]

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• Anaphylaxis caused by casein used in artificially marbled beef: A case report

  S. Narabayashi, I. Okafuji, Y. Tanaka, S. Tsuruta, N. Takamatsu

  Allergology International (2016).

  
  

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• Cross-reactivity between major IgE core epitopes on Cry j 2 allergen of Japanese cedar pollen and relevant sequences on Cha o 2 allergen of Japanese cypress pollen

  K. Miyaji, N. Okamoto, A. Saito, H. Yasueda, Y. Takase, H. Shimakura, S. Saito, M. Sakaguchi

  Allergology International (2016).

  
  

  Abstract

  Cry j 2 and Cha o 2 are major allergens in Japanese cedar (Cryptomeria japonica; CJ) and Japanese cypress (Chamaecyparis obtusa; CO) pollen, respectively. Here, we assessed the epitopes related to the cross-reactivity between Cry j 2 and Cha o 2 using in vitro analyses. Peptides were synthesized based on Cry j 2 sequential epitopes and relevant Cha o 2 amino acid sequences. Four representative monoclonal antibodies (mAbs) against Cry j 2 were used according to their epitope recognitions. Serum samples were collected from 31 patients with CJ pollinosis. To investigate cross-reactivity between Cry j 2 and Cha o 2, ELISA and inhibition ELISA were performed with mAbs and sera from patients with CJ pollinosis. Two of four mAbs had reactivity to both Cry j 2 and Cha o 2. Of these two mAbs, one mAb (T27) recognized the amino acid sequence 169KVVNGRTV176 on Cha o 2. This is related to the core epitope 169KWVNGREI176 on Cry j 2, which is an important IgE epitope. In addition, we found that these correlative sequences and purified allergens showed cross-reactivity between Cry j 2 and Cha o 2 in IgE of CJ patients. We demonstrated the importance of 169KVVNGRTV176 in Cha o 2 for cross-reactivity with the Cry j 2 epitope 169KWVNGREI176, which plays an important role in allergenicity in CJ pollinosis. Our results are useful for the development of safer and more efficient therapeutic strategies for the treatment of CJ and CO pollen allergies.

  Abstract
  Cry j 2 and Cha o 2 are major allergens in Japanese cedar (Cryptomeria japonica; CJ) and Japanese cypress (Chamaecyparis obtusa; CO) pollen, respectively. Here, we assessed [...]

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• Filaggrin exists in human nose

  M. Miwa, S. Hasan, M. Miwa, K. Okubo

  Allergology International (2016).

  
  

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• Persistently high exhaled nitric oxide and loss of lung function in controlled asthma

  K. Matsunaga, T. Hirano, A. Oka, K. Ito, N. Edakuni

  Allergology International (2016).

  
  

  Abstract

  It remains unclear whether a persistently high exhaled nitric oxide fraction (FeNO) in patients with controlled asthma is associated with the progressive loss of lung function. This was a 3-year prospective study. We examined the changes in pre- and post-bronchodilator forced expiratory volume in 1 s (FEV1) and FeNO in 140 patients with controlled asthma. We initially determined the FeNO cut-off point for identifying patients with a rapid decline in FEV1 (>40 mL/yr). Next, a total of 122 patients who maintained high or non-high FeNO were selected, and the associations between the FeNO trend and changes in FEV1 and bronchodilator response (BDR) were investigated. A FeNO level >40.3 ppb yielded 43% sensitivity and 86% specificity for identifying patients with a rapid decline in FEV1. Patients with persistently high FeNO had higher rates of decline in FEV1 (42.7 ± 37.5 mL/yr) than patients with non-high FeNO (16.7 ± 31.5 mL/yr) (p 

  Abstract
  It remains unclear whether a persistently high exhaled nitric oxide fraction (FeNO) in patients with controlled asthma is associated with the progressive loss of lung function. [...]

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• Reactive airways dysfunction syndrome after hydrofluoric acid inhalation

  T. Lee, H. Yoo, S. Bae, M. Kim, G. Kim, A. Jang

  Allergology International (2016).

  
  

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• In vivo imaging in autoimmune diseases in the central nervous system

  N. Kawakami

  Allergology International (2016).

  
  

  Abstract

  Intravital imaging is becoming more popular and is being used to visualize cellular motility and functions. In contrast to in vitro analysis, which resembles in vivo analysis, intravital imaging can be used to observe and analyze cells directly in vivo. In this review, I will summarize recent imaging studies of autoreactive T cell infiltration into the central nervous system (CNS) and provide technical background. During their in vivo journey, autoreactive T cells interact with many different cells. At first, autoreactive T cells interact with endothelial cells in the airways of the lung or with splenocytes, where they acquire a migratory phenotype to infiltrate into the CNS. After arriving at the CNS, they interact with endothelial cells of the leptomeningeal vessels or the choroid plexus before passing through the blood–brain barrier. CNS-infiltrating T cells become activated by recognizing endogenous autoantigens presented by local antigen-presenting cells (APCs). This activation was visualized in vivo by using protein-based sensors. One such sensor detects changes in intracellular calcium concentration as an early marker of T cell activation. Another sensor detects translocation of Nuclear factor of activated T-cells (NFAT) from cytosol to nucleus as a definitive sign of T cell activation. Importantly, intravital imaging is not just used to visualize cellular behavior. Together with precise analysis, intravital imaging deepens our knowledge of cellular functions in living organs and also provides a platform for developing therapeutic treatments.

  Abstract
  Intravital imaging is becoming more popular and is being used to visualize cellular motility and functions. In contrast to in vitro analysis, which resembles in vivo analysis, [...]

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