Details of a Researcher - OGASAWARA Noriko

Papers - OGASAWARA Noriko

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TNF induces production of type 2 cytokines in human group 2 innate lymphoid cells.

Noriko Ogasawara, Julie A Poposki, Aiko I Klingler, Bruce K Tan, Kathryn E Hulse, Whitney W Stevens, Anju T Peters, Leslie C Grammer, Kevin C Welch, Stephanie S Smith, David B Conley, Ken-Ichi Takano, Tetsuo Himi, Robert C Kern, Robert P Schleimer, Atsushi Kato

The Journal of allergy and clinical immunology 145 ( 1 ) 437 - 440 2020.01 [Refereed] [International journal]

DOI PubMed

Role of RANK-L as a potential inducer of ILC2-mediated type 2 inflammation in chronic rhinosinusitis with nasal polyps.

Noriko Ogasawara, Julie A Poposki, Aiko I Klingler, Bruce K Tan, Kathryn E Hulse, Whitney W Stevens, Anju T Peters, Leslie C Grammer, Kevin C Welch, Stephanie S Smith, David B Conley, Joseph R Raviv, Pejman Soroosh, Ken-Ichi Takano, Tetsuo Himi, Robert C Kern, Robert P Schleimer, Atsushi Kato

Mucosal immunology 13 ( 1 ) 86 - 95 2020.01 [Refereed] [International journal]

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by type 2 inflammation with accumulation of activated group 2 innate lymphoid cells (ILC2s) and elevation of thymic stromal lymphopoietin (TSLP). A member of the TNF superfamily (TNFSF), TNFSF15, is known to induce the production of type 2 cytokines in ILC2s. Although ILC2s have been implicated in CRSwNP, the presence and role of TNFSFs in ILC2-mediated type 2 inflammation in CRSwNP has not been elucidated. Here, we investigate the involvement of TNFSFs in ILC2-mediated type 2 inflammation in CRSwNP. We found that receptor activator of NF-κB (RANK) ligand (RANK-L (TNFSF11)) was significantly elevated in nasal polyps (NPs), and that the receptor of RANK-L, RANK, was expressed on ILC2s in human peripheral blood and NPs. An agonistic antibody against RANK induced production of type 2 cytokines in human ILC2s, and TSLP significantly enhanced this reaction. The membrane-bound RANK-L was detected mainly on CD45 + immune cells, including TH2 cells in NPs. The co-culture of NP-derived ILC2s and TH2 cells significantly enhanced production of type 2 cytokines, and anti-RANK-L monoclonal antibody suppressed this enhancement. In conclusion, RANK-L, together with TSLP, may play an inductive role in the ILC2-mediated type 2 inflammation in CRSwNP.

DOI PubMed

Epithelial activators of type 2 inflammation: Elevation of thymic stromal lymphopoietin, but not IL-25 or IL-33, in chronic rhinosinusitis with nasal polyps in Chicago, Illinois.

Noriko Ogasawara, Aiko I Klingler, Bruce K Tan, Julie A Poposki, Kathryn E Hulse, Whitney W Stevens, Anju T Peters, Leslie C Grammer, Kevin C Welch, Stephanie S Smith, David B Conley, Robert C Kern, Robert P Schleimer, Atsushi Kato

Allergy 73 ( 11 ) 2251 - 2254 2018.11 [Refereed] [International journal]

DOI PubMed

Up-regulation of serum periostin and squamous cell carcinoma antigen levels in infants with acute bronchitis due to respiratory syncytial virus.

Hiroaki Nakamura, Kenichi Akashi, Masako Watanabe, Shoichiro Ohta, Junya Ono, Yoshinori Azuma, Noriko Ogasawara, Keisuke Yamamoto, Norikazu Shimizu, Hiroyuki Tsutsumi, Kenji Izuhara, Toshio Katsunuma

Allergology international : official journal of the Japanese Society of Allergology 67 ( 2 ) 259 - 265 2018.04 [Refereed] [International journal]

BACKGROUND: Periostin and squamous cell carcinoma antigen (SCCA) are involved in the pathogenesis of asthma. Acute bronchitis due to respiratory syncytial virus (RSV) infection during infancy exhibits an asthma-like pathogenesis, suggesting that it may be associated with the subsequent development of asthma. However, the mechanism by which RSV infection leads to development of asthma has not yet been fully elucidated. METHODS: Infants younger than 36 months were enrolled and classified into three groups. Group I included patients hospitalized with RSV-induced bronchitis. These patients were further stratified into two sub-groups according to whether the criteria for the modified Asthma Predictive Index (mAPI) had been met: Group I consisted of mAPI (+) and mAPI (-) patients; Group II included patients with food allergy as a positive control group; and Group III included children with no allergy as a negative control group. Serum periostin and SCCA levels were measured in the groups. This study was registered as a clinical trial (UMIN000012339). RESULTS: We enrolled 14 subjects in Group I mAPI (+), 22 in Group I mAPI (-), 18 in Group II, and 18 in Group III. In Group I, the serum periostin and SCCA levels were significantly higher during the acute phase compared with the recovery phase. However, no significant differences were found between Group I mAPI (+) and mAPI (-). CONCLUSIONS: The serum periostin and SCCA levels increased during acute RSV bronchitis. Both periostin and SCCA may play a role in the pathogenesis of acute bronchitis due to RSV.

DOI PubMed

IL-10, TGF-β, and glucocorticoid prevent the production of type 2 cytokines in human group 2 innate lymphoid cells.

Noriko Ogasawara, Julie A Poposki, Aiko I Klingler, Bruce K Tan, Ava R Weibman, Kathryn E Hulse, Whitney W Stevens, Anju T Peters, Leslie C Grammer, Robert P Schleimer, Kevin C Welch, Stephanie S Smith, David B Conley, Joseph R Raviv, Pejman Soroosh, Omid Akbari, Tetsuo Himi, Robert C Kern, Atsushi Kato

The Journal of allergy and clinical immunology ( Mosby Inc. ) 141 ( 3 ) 1147 - 1151 2018.03 [Refereed] [International journal]

DOI PubMed

Evaluation of consistency in quantification of gene copy number by real-time reverse transcription quantitative polymerase chain reaction and virus titer by plaque-forming assay for human respiratory syncytial virus.

Keisuke Yamamoto, Noriko Ogasawara, Soh Yamamoto, Kenichi Takano, Tsukasa Shiraishi, Toyotaka Sato, Hiroyuki Tsutsumi, Tetsuo Himi, Shin-Ichi Yokota

Microbiology and immunology 62 ( 2 ) 90 - 98 2018.02 [Refereed] [International journal]

The plaque-forming assay is the standard technique for determining viral titer, and a critical measurement for investigating viral replication. However, this assay is highly dependent on experimental technique and conditions. In the case of human respiratory syncytial virus (RSV) in particular, it can be difficult to objectively confirm the accuracy of plaque-forming assay because the plaques made by RSV are often small and unclear. In recent studies, RT-qPCR methods have emerged as a supportive procedure for assessment of viral titer, yielding highly sensitive and reproducible results. In this report, we compare the viral replication, as determined by plaque-forming assay, and the copy numbers of RSV genes NS1, NS2, N, and F, as determined by RT-qPCR. Two real-time PCR systems, SYBR Green and TaqMan probe, gave highly similar results for measurement of copy numbers of RSV N genes of virus subgroups A. We determined the RSV gene copy numbers in the culture cell supernatant and cell lysate measured at various multiplicities of infection. We found that copy number of the RSV N gene in the culture supernatant and cell lysate was highly correlated with plaque-forming units. In conclusion, RT-qPCR measurement of RSV gene copy number was highly dependent on viral titer, and the detailed comparison between each gene copy number and virus titer should be useful and supportive in confirming RSV plaque-forming assay and virus dynamics. The technique may also be used to estimate the amount of RSV present in clinical specimens.

DOI PubMed

Mitochondrial proteins NIP-SNAP-1 and -2 are a target for the immunomodulatory activity of clarithromycin, which involves NF-κB-mediated cytokine production.

Soh Yamamoto, Noriko Ogasawara, Keisuke Yamamoto, Chika Uemura, Yoshiaki Takaya, Tsukasa Shiraishi, Toyotaka Sato, Shin Hashimoto, Hiroyuki Tsutsumi, Kenichi Takano, Tetsuo Himi, Shin-Ichi Yokota

Biochemical and biophysical research communications ( ACADEMIC PRESS INC ELSEVIER SCIENCE ) 483 ( 3 ) 911 - 916 2017.02 [Refereed] [International journal]

Macrolide antibiotics have immunomodulatory activities, including suppression of cytokine production, cell adhesion molecule expression, and mucin production. These immunomodulatory activities improve the symptoms of respiratory diseases associated with chronic inflammation. However, the underlying molecular mechanism(s) is not well understood yet. To address this, we prepared clarithromycin (CAM)-conjugated Sepharose and examined bound cellular proteins by proteome analysis. We identified mitochondrial proteins 4-nitrophenylphosphatase domain and non-neuronal synaptosomal associated protein 25-like protein homolog (NIP-SNAP)-1 and -2 and very long-chain acyl-CoA dehydrogenase (VLCAD) as CAM-binding proteins. Production of proinflammatory cytokines (IL-8 and IL-6) induced by lipopolysaccharides (LPSs) and Pam3-CSK4 in human epithelial cell lines BEAS-2B and T24 were suppressed by knockdown of NIP-SNAP-1 or -2, and partly by knockdown of VLCAD. Also, knockdown of NIP-SNAP-1 or -2 in various cell lines suppressed LPS-induced expression of IL-8 and IL-6 mRNA and NF-κB activity. Thus, CAM suppresses NF-κB-mediated proinflammatory cytokine production by interacting with mitochondrial proteins, NIP-SNAP-1 and -2.

DOI PubMed

NIP-SNAP-1 and -2 mitochondrial proteins are maintained by heat shock protein 60.

Soh Yamamoto, Tomoya Okamoto, Noriko Ogasawara, Shin Hashimoto, Tsukasa Shiraishi, Toyotaka Sato, Keisuke Yamamoto, Hiroyuki Tsutsumi, Kenichi Takano, Testuo Himi, Hideaki Itoh, Shin-Ichi Yokota

Biochemical and biophysical research communications ( ACADEMIC PRESS INC ELSEVIER SCIENCE ) 483 ( 3 ) 917 - 922 2017.02 [Refereed] [International journal]

NIP-SNAP-1 and -2 are ubiquitous proteins thought to be associated with maintenance of mitochondrial function, neuronal transmission, and autophagy. However, their physiological functions remain largely unknown. To elucidate their functional importance, we screened for proteins that interact with NIP-SNAP-1 and -2, resulting in identification of HSP60 and P62/SQSTM1 as binding proteins. NIP-SNAP-1 and -2 localized in the mitochondrial inner membrane space, whereas HSP60 localized in the matrix. Native gel electrophoresis and filter trap assays revealed that human HSP60 prevented aggregation of newly synthesized NIP-SNAP-2 in an in vitro translation system. Moreover, expression levels of NIP-SNAP-1 and -2 in cells were decreased by knockdown of HSP60, but not HSP10. These findings indicate that HSP60 promotes folding and maintains the stability of NIP-SNAP-1 and -2.

DOI PubMed

Clarithromycin prevents human respiratory syncytial virus-induced airway epithelial responses by modulating activation of interferon regulatory factor-3

Keisuke Yamamoto, Soh Yamamoto, Noriko Ogasawara, Kenichi Takano, Tsukasa Shiraishi, Toyotaka Sato, Ryo Miyata, Takuya Kakuki, Ryuta Kamekura, Takashi Kojima, Hiroyuki Tsutsumi, Tetsuo Himi, Shin-ichi Yokota

PHARMACOLOGICAL RESEARCH ( ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD ) 111 804 - 814 2016.09 [Refereed]

Macrolide antibiotics exert immunomodulatory activity by reducing pro-inflammatory cytokine production by airway epithelial cells, fibroblasts, vascular endothelial cells, and immune cells. However, the underlying mechanism of action remains unclear. Here, we examined the effect of clarithromycin (CAM) on pro-inflammatory cytokine production, including interferons (IFNs), by primary human nasal epithelial cells and lung epithelial cell lines (A549 and BEAS-2B cells) after stimulation by Toll-like receptor (TLR) and RIG-I-like receptor (RLR) agonists and after infection by human respiratory syncytial virus (RSV). CAM treatment led to a significant reduction in poly I:C-and RSV-mediated IL-8, CCL5, IFN-beta and -lambda production. Furthermore, IFN-beta promoter activity (activated by poly I:C and RSV infection) was significantly reduced after treatment with CAM. CAM also inhibited IRF-3 dimerization and subsequent translocation to the nucleus. We conclude that CAM acts a crucial modulator of the innate immune response, particularly IFN production, by modulating IRF-3 dimerization and subsequent translocation to the nucleus of airway epithelial cells. This newly identified immunomodulatory action of CAM will facilitate the discovery of new macrolides with an anti-inflammatory role. (C) 2016 Elsevier Ltd. All rights reserved.

DOI PubMed

Rapid and Integrated Bacterial Evolution Analysis unveils gene mutations and clinical risk of Klebsiella pneumoniae.

Kojiro Uemura, Toyotaka Sato, Soh Yamamoto, Noriko Ogasawara, Jirachaya Toyting, Kotaro Aoki, Akira Takasawa, Masayuki Koyama, Atsushi Saito, Takayuki Wada, Kaho Okada, Yurie Yoshida, Koji Kuronuma, Chie Nakajima, Yasuhiko Suzuki, Motohiro Horiuchi, Kenichi Takano, Satoshi Takahashi, Hirofumi Chiba, Shin-Ichi Yokota

Nature communications 16 ( 1 ) 2917 - 2917 2025.03 [International journal]

Bacteria continually evolve. Previous studies have evaluated bacterial evolution in retrospect, but this approach is based on only speculation. Cohort studies are reliable but require a long duration. Additionally, identifying which genetic mutations that have emerged during bacterial evolution possess functions of interest to researchers is an exceptionally challenging task. Here, we establish a Rapid and Integrated Bacterial Evolution Analysis (RIBEA) based on serial passaging experiments using hypermutable strains, whole-genome and transposon-directed sequencing, and in vivo evaluations to monitor bacterial evolution in a cohort for one month. RIBEA reveals bacterial factors contributing to serum and antimicrobial resistance by identifying gene mutations that occurred during evolution in the major respiratory pathogen Klebsiella pneumoniae. RIBEA also enables the evaluation of the risk for the progression and the development of invasive ability from the lung to blood and antimicrobial resistance. Our results demonstrate that RIBEA enables the observation of bacterial evolution and the prediction and identification of clinically relevant high-risk bacterial strains, clarifying the associated pathogenicity and the development of antimicrobial resistance at genetic mutation level.

DOI PubMed

Bacillaceae serine proteases and Streptomyces epsilon-poly-l-lysine synergistically inactivate Caliciviridae by inhibiting RNA genome release

Soh Yamamoto, Noriko Ogasawara, Yuka Sudo-Yokoyama, Sachiko Sato, Nozomu Takata, Nana Yokota, Tomomi Nakano, Kyoko Hayashi, Akira Takasawa, Mayumi Endo, Masako Hinatsu, Keitaro Yoshida, Toyotaka Sato, Satoshi Takahashi, Kenichi Takano, Takashi Kojima, Jun Hiraki, Shin-ich Yokota

Scientific Reports ( Springer Science and Business Media LLC ) 14 ( 1 ) 2024.07

Abstract Human norovirus (HuNoV) is an enteric infectious pathogen belonging to the Caliciviridae family that causes occasional epidemics. Circulating alcohol-tolerant viral particles that are readily transmitted via food-borne routes significantly contribute to the global burden of HuNoV-induced gastroenteritis. Moreover, contact with enzymes secreted by other microorganisms in the environment can impact the infectivity of viruses. Hence, understanding the circulation dynamics of Caliciviridae is critical to mitigating epidemics. Accordingly, in this study, we screened whether environmentally abundant secretase components, particularly proteases, affect Caliciviridae infectivity. Results showed that combining Bacillaceae serine proteases with epsilon-poly-l-lysine (EPL) produced by Streptomyces—a natural antimicrobial—elicited anti-Caliciviridae properties, including against the epidemic HuNoV GII.4_Sydney_2012 strain. In vitro and in vivo biochemical and virological analyses revealed that EPL has two unique synergistic viral inactivation functions. First, it maintains an optimal pH to promote viral surface conformational changes to the protease-sensitive structure. Subsequently, it inhibits viral RNA genome release via partial protease digestion at the P2 and S domains in the VP1 capsid. This study provides new insights regarding the high-dimensional environmental interactions between bacteria and Caliciviridae, while promoting the development of protease-based anti-viral disinfectants.

DOI

The clarithromycin-binding proteins NIPSNAP1 and 2 regulate cytokine production through mitochondrial quality control.

Soh Yamamoto, Noriko Ogasawara, Yukari Mitsuhashi, Kenichi Takano, Shin-Ichi Yokota

Scientific reports 14 ( 1 ) 2354 - 2354 2024.01 [International journal]

The mechanism underlying the anti-inflammatory effect of macrolide antibiotics, such as clarithromycin (CAM), remains to be clarified. The CAM-binding proteins 4-nitrophenylphosphatase domain and non-neuronal synaptosomal associated protein 25 (SNAP25)-like protein homolog (NIPSNAP) 1 and 2 are involved in the immune response and mitochondrial homeostasis. However, the axis between CAM-NIPSNAP-mitochondria and Toll-like receptor (TLR) and their molecular mechanisms remain unknown. In this study, we sought to elucidate the relationship between mitochondrial homeostasis mediated by NIPSNAP1 and 2 and the immunomodulatory effect of CAM. NIPSNAP1 or 2 knockdown (KD) by RNA interference impaired TLR4-mediated interleukin-8 (IL-8) production. Similar impairment was observed upon treatment with mitochondrial function inhibitors. However, IL-8 secretion was not impaired in NIPSNAP1 and 2 individual knockout (KO) and double KO (DKO) cells. Moreover, the oxygen consumption rate (OCR) in mitochondria measured using a flex analyzer was significantly reduced in NIPSNAP1 or 2 KD cells, but not in DKO cells. CAM also dose-dependently reduced the OCR. These results indicate that CAM suppresses the IL-8 production via the mitochondrial quality control regulated by temporary functional inhibition of NIPSNAP1 and 2. Our findings provide new insight into the mechanisms underlying cytokine production, including the TLR-mitochondria axis, and the immunomodulatory effects of macrolides.

DOI PubMed

Affinity of β-Lactam Antibiotics for Neisseria gonorrhoeae Penicillin-Binding Protein 2 Having Wild, Cefixime-Reduced-Susceptible, and Cephalosporin (Ceftriaxone)-Resistant penA Alleles.

Yoshiki Hiyama, Soh Yamamoto, Toyotaka Sato, Noriko Ogasawara, Naoya Masumori, Satoshi Takahashi, Shin-Ichi Yokota

Microbial drug resistance (Larchmont, N.Y.) 2024.01 [International journal]

Multidrug-resistant Neisseria gonorrhoeae is a serious concern worldwide. Resistance to β-lactam antibiotics occurs through mutations in penicillin-binding proteins (PBPs), acquisition of β-lactamases, and alteration of antibiotic penetration. Mosaic structures of penA, which encodes PBP2, play a major role in resistance to β-lactams, especially cephalosporins. Ceftriaxone (CRO) is recognized as the only satisfiable antibiotic for the treatment of gonococcal infections; however, CRO-resistant isolates have emerged in the community. Here, we examined the affinity of β-lactam antibiotics for recombinant PBP2 in a competition assay using fluorescence-labeled penicillin. We found no or little difference in the affinities of penicillins and meropenem (MEM) for PBP2 from cefixime (CFM)-reduced-susceptible strain and cephalosporin-resistant strain. However, the affinity of cephalosporins, including CRO, for PBP2 from the cephalosporin-resistant strain was markedly lower than that for PBP2 from the CFM-reduced-susceptible-resistant strain. Notably, piperacillin (PIP) showed almost the same affinity for PBP2 from penicillin-susceptible, CFM-reduced-susceptible, and cephalosporin (including CRO)-resistant strains. Thus, PIP/tazobactam and MEM are candidate antibiotics for the treatment of CRO-resistant/multidrug-resistant N. gonorrhoeae.

DOI PubMed

Serotype replacement and an increase in non-encapsulated isolates among community-acquired infections of Streptococcus pneumoniae during post-vaccine era in Japan.

Shin-Ichi Yokota, Naoyuki Tsukamoto, Toyotaka Sato, Yasuo Ohkoshi, Soh Yamamoto, Noriko Ogasawara

IJID regions 8 105 - 110 2023.09 [International journal]

OBJECTIVES: It is feared that the serotype replacement of Streptococcus pneumoniae occurred by the introduction of pneumococcal vaccines as periodical inoculation leads to reduced efficacy of the approved vaccines and altered antimicrobial susceptibility. METHODS: We determined serotypes of 351 S. pneumoniae isolates collected at a commercial clinical laboratory in Hokkaido prefecture, Japan, from December 2018 to February 2019 by using the polymerase chain reaction procedure of the US Centers for Disease Control and Prevention. Antimicrobial susceptibility and resistance gene profiles were also examined. RESULTS: Vaccine coverage rates were 7.9% for 13-valent conjugate vaccine, and 32.5% for 23-valent polysaccharide vaccine, respectively. Non-typable strains were 19.7%. cpsA-positive isolates (group I), and null capsule clade (NCC)1, NCC2 and NCC3 (group II) comprised 31.3%, 28.4%, 32.8%, and 7.5% of the 69 non-typable strains, respectively. No penicillin-resistant/intermediate isolates were found; however, serotypes 35B and 15A/F showed low susceptibility to β-lactams. Only five strains (1.4%) were levofloxacin-resistant, and all were from the older persons, and three strains were serotype 35B. CONCLUSION: The progression of serotype replacement in non-invasive pneumococcal infections has occurred during the post-vaccine era in Japan, and non-encapsulated isolates, such as NCC, have increased. Antimicrobial susceptibility is not worsened.

DOI PubMed

当院における人工内耳装用者(児)への遠隔地マッピングの取り組み

海崎文, 新谷朋子, 才川悦子, 小笠原徳子, 木村綾美, 佐藤楓, 高野賢一

Audiology Japan ( (一社)日本聴覚医学会 ) 66 ( 5 ) 370 - 370 2023.09

片耳伝音難聴の軟骨伝導補聴器試聴から装用の現状

木村綾美, 新谷朋子, 才川悦子, 小笠原徳子, 海崎文, 佐藤楓, 高野賢一

Audiology Japan ( (一社)日本聴覚医学会 ) 66 ( 5 ) 426 - 426 2023.09

High prevalence of colistin heteroresistance in specific species and lineages of Enterobacter cloacae complex derived from human clinical specimens.

Shota Fukuzawa, Toyotaka Sato, Kotaro Aoki, Soh Yamamoto, Noriko Ogasawara, Chie Nakajima, Yasuhiko Suzuki, Motohiro Horiuchi, Satoshi Takahashi, Shin-Ichi Yokota

Annals of clinical microbiology and antimicrobials 22 ( 1 ) 60 - 60 2023.07 [International journal]

BACKGROUND: Colistin (CST) is a last-line drug for multidrug-resistant Gram-negative bacterial infections. CST-heteroresistant Enterobacter cloacae complex (ECC) has been isolated. However, integrated analysis of epidemiology and resistance mechanisms based on the complete ECC species identification has not been performed. METHODS: Clinical isolates identified as "E. cloacae complex" by MALDI-TOF MS Biotyper Compass in a university hospital in Japan were analyzed. Minimum inhibitory concentrations of CST were determined by the broth microdilution method. The population analysis profiling (PAP) was performed for detecting the heteroresistant phenotype. The heat shock protein 60 (hsp60) cluster was determined from its partial nucleotide sequence. From the data of whole-genome sequencing, average nucleotide identity (ANI) for determining ECC species, multilocus sequence type, core genome single-nucleotide-polymorphism-based phylogenetic analysis were performed. phoPQ-, eptA-, and arnT-deleted mutants were established to evaluate the mechanism underlying colistin heteroresistance. The arnT mRNA expression levels were determined by reverse transcription quantitative PCR. RESULTS: Thirty-eight CST-resistant isolates, all of which exhibited the heteroresistant phenotype by PAP, were found from 138 ECC clinical isolates (27.5%). The prevalence of CST-resistant isolates did not significantly differ among the origin of specimens (29.0%, 27.8%, and 20.2% for respiratory, urine, and blood specimens, respectively). hsp60 clusters, core genome phylogeny, and ANI revealed that the CST-heteroresistant isolates were found in all or most of Enterobacter roggenkampii (hsp60 cluster IV), Enterobacter kobei (cluster II), Enterobacter chuandaensis (clusters III and IX), and Enterobacter cloacae subspecies (clusters XI and XII). No heteroresistant isolates were found in Enterobacter hormaechei subspecies (clusters VIII, VI, and III) and Enterobacter ludwigii (cluster V). CST-induced mRNA upregulation of arnT, which encodes 4-amino-4-deoxy-L-arabinose transferase, was observed in the CST-heteroresistant isolates, and it is mediated by phoPQ pathway. Isolates possessing mcr-9 and mcr-10 (3.6% and 5.6% of total ECC isolates, respectively) exhibited similar CST susceptibility and PAP compared with mcr-negative isolates. CONCLUSIONS: Significant prevalence (approximately 28%) of CST heteroresistance is observed in ECC clinical isolates, and they are accumulated in specific species and lineages. Heteroresistance is occurred by upregulation of arnT mRNA induced by CST. Acquisition of mcr genes contributes less to CST resistance in ECC.

DOI PubMed

Colistin-resistant bacteria poses few risks under physiological conditions

Soh Yamamoto, Masaru Usui, Noriko Ogasawara, Wataru Hayashi, Masato Suzuki, Noriyuki Nagano, Chie Nakajima, Yasuhiko Suzuki, Motohiro Horiuchi, Satoshi Takahashi, Shin-ichi Yokota, Yutaka Tamura, Toyotaka Sato

Research Square ( Research Square Platform LLC ) 2023.06

Abstract Globally, 5.0 million people die annually from infections associated with antimicrobial-resistant bacteria, most commonly Escherichia coli¹. As colistin is a last-resort antibiotic for multidrug-resistant bacterial infections, the global spread of plasmid-mediated colistin resistance genes (mcr) gene is considered a major public health risk^2-4. However, the actual health risks of colistin resistance in hazardous bacteria have never been evaluated under physiological conditions. Here, we show that the fitness/virulence and colistin resistance of the pandemic multidrug-resistant E. coli clone ST131⁵ very depending on the acquired colistin resistance determinants and differ between physiological and in vitro conditions. The fitness/virulence of ST131 was unaffected by chromosomal-gene (pmrB) mutations or the acquisition of mcr-5-harbouring plasmids in mouse models. However, the acquisition of mcr-1- or mcr-3-harbouring plasmids attenuated fitness/virulence and promoted colistin susceptibility in human serum. We identified two virulence attenuation factors (vafA and vafB) on the pIncI2_mcr-1 plasmid that hijacked the ST131 transcriptome and inhibited nucleotide synthesis, attenuating colistin resistance. Our results demonstrate that colistin resistance poses much less of a threat than believed^6,7. We suggest that “nonresistance genes,” rather than resistance genes, are important antimicrobial resistance determinants for human health because they determine fitness/virulence and ultimately antimicrobial susceptibility under physiological conditions.

DOI

Rapid, simple, and cost-effective plaque assay for murine norovirus using microcrystalline cellulose.

Soh Yamamoto, Yuka Sudo-Yokoyama, Noriko Ogasawara, Shin-Ichi Yokota

Journal of virological methods 316 114715 - 114715 2023.06 [International journal]

Murine norovirus (MNV) is used widely as a practical alternative to human norovirus (HuNoV). Plaque-forming assays for MNV are important for developing therapeutic agents against HuNoV infections. Although agarose-overlay MNV assays have been reported, recent improvements in cellulose derivatives suggest that they could be optimized further, particularly with respect to improving the overlay material. To determine which overlay material is optimal for the MNV plaque assay, we compared four typical cellulose derivatives [microcrystalline cellulose (MCC), hydroxyethyl cellulose (HEC), hydroxypropyl methylcellulose (HPMC), and carboxymethyl cellulose (CMC)] with conventional agarose. We found that 3.5% (w/v) MCC-containing medium provided clear round-shaped plaques on RAW 264.7 cells 1 day after inoculation; the visibility of plaques was comparable with that of the original agarose-overlay assay. Removing residual MCC powder from the MCC-overlay assay before fixing was important for obtaining distinct plaques that are clearly countable. Finally, after calculating the plaque diameter as a percentage of well diameter, we found that 12- and 24-well plates were better than other plates for accurate plaque counting. The MCC-based MNV plaque assay is cost-effective and rapid, and produces plaques that are easy to count. Accurate virus quantification using this optimized plaque assay will enable reliable estimation of norovirus titers.

DOI PubMed

抗菌性物質・薬剤耐性/生体防御大腸菌ST131におけるmcr-1保有プラスミドの獲得による病原性減弱機構(Antimicrobial agents and resistance/Host defense Virulent attenuation mechanism by acquisition of mcr-1-harboring plasmid into Escherichia coli ST131)

佐藤豊孝, 山本聡, 小笠原徳子, 臼井優, 長野則之, 土井洋平, 堀内基広, 高橋聡, 横田伸一, 田村豊

日本細菌学雑誌 ( 日本細菌学会 ) 78 ( 1 ) 48 - 48 2023.02

COVID-19における嗅裂閉鎖所見と嗅覚障害の検討

山本圭佑, 藤谷好弘, 山直也, 黒沼幸治, 小笠原徳子, 横田伸一, 高橋聡, 高野賢一

日本耳鼻咽喉科免疫アレルギー感染症学会誌 ( 日本耳鼻咽喉科免疫アレルギー感染症学会 ) 2 ( 2 ) 49 - 54 2022.06

A Hydroxypropyl Methylcellulose Plaque Assay for Human Respiratory Syncytial Virus.

Yuka Takumi-Tanimukai, Soh Yamamoto, Noriko Ogasawara, Sayaka Nakabayashi, Katsumi Mizuta, Keisuke Yamamoto, Ryo Miyata, Takuya Kakuki, Sumito Jitsukawa, Toyotaka Sato, Hiroyuki Tsutsumi, Takashi Kojima, Kenichi Takano, Shin-Ichi Yokota

Journal of virological methods 304 114528 - 114528 2022.03 [International journal]

Quantifying proliferative virus particles is one of the most important experimental procedures in virology. Compared with classical overlay materials, newly developed cellulose derivatives enable a plaque-forming assay to produce countable clear plaques easily. HEp-2 cells are widely used in plaque assays for human respiratory syncytial virus (RSV). It is crucial to use an overlay material to keep HEp-2 cell proliferation and prevent RSV particles from spreading over the fluid. Among four cellulose derivatives, carboxymethyl cellulose sodium salt (CMC), hydroxypropyl methylcellulose (HPMC), microcrystalline cellulose (MCC), and hydroxyethyl cellulose (HEC), we found that HPMC was the optimal overlay material because HPMC maintained HEp-2 cell proliferation and RSV infectivity. Although MCC was unsuitable for RSV, it assisted the plaque-forming by human metapneumovirus in TMPRSS2-expressing cells. Therefore, depending on the cells and viruses, it is necessary to use different overlay materials at varying concentrations.

DOI PubMed

[ROLE OF GROUP 2 INNATE LYMPHOID CELLS IN ALLERGIC INFLAMMATION OF THE UPPER RESPIRATORY TRACT].

Noriko Ogasawara, Atsushi Kato

Arerugi = [Allergy] 71 ( 3 ) 195 - 199 2022 [Domestic journal]

DOI PubMed

Self-reported Smell and Taste Disorders in Patients With COVID-19: A Japanese Single-center Study.

Keisuke Yamamoto, Yoshihiro Fujiya, Koji Kuronuma, Noriko Ogasawara, Tsuyoshi Ohkuni, Shin-Ichi Yokota, Satoshi Takahashi, Kenichi Takano

In vivo (Athens, Greece) 36 ( 2 ) 918 - 924 2022 [International journal]

BACKGROUND/AIM: Smell and taste disorders are among the most common symptoms of COVID-19. However, the relationship between smell and taste disorders and systemic symptoms is not fully understood in Japan. PATIENTS AND METHODS: Questionnaires were mailed to 105 of 111 COVID-19 patients who were hospitalized at our hospital between March and July 2020 in Japan. RESULTS: A total of 74 patients (response rate: 70.5%) completed the survey. Of these, six patients (8.1%) presented with smell disorders only, 16 (21.6%) presented with taste disorders only, and 17 (23.0%) presented with both smell and taste disorders. The mean Visual Analog Scale for smell and taste was 0.5 and 20, respectively, at the time of the most severe symptoms. CONCLUSION: Among COVID-19 patients in Japan, smell and taste disorders are often followed by fever and may not be the first symptoms. Sense of smell is particularly impaired. These symptoms often improve, although they sometimes persist for a long time as sequelae.

DOI PubMed

Reduction of susceptibility to azoles and 5-fluorocytosine and growth acceleration in Candida albicans in glucosuria.

Yoshiki Hiyama, Toyotaka Sato, Satoshi Takahashi, Soh Yamamoto, Noriko Ogasawara, Naoya Masumori, Shin-Ichi Yokota

Diagnostic microbiology and infectious disease 102 ( 1 ) 115556 - 115556 2021.09 [International journal]

Diabetes mellitus is a chronic metabolic disease characterized by hyperglycemia and glucosuria, and is a risk factor for Candida infections. To reveal the potential effects of glucosuria on Candida spp., we investigated their growth and antifungal susceptibilities in normal human urine to which glucose was added. The viable cell numbers of Candida spp. were more than 10 fold higher in the urine added 3000 mg/dL glucose than in plain urine. In antifungal susceptibility, more than 80% of Candida albicans clinical isolates increased minimum inhibitory concentrations of azoles and 5-fluorocytosine with the addition of glucose, and exceeded their breakpoints. In most of the C. albicans clinical isolates, the mRNA expression of the azole resistance genes ERG11, CDR1, CDR2, and MDR1 in the presence of glucose in urine. These observations provide valuable information about the clinical course and therapeutic effects of azoles against C. albicans infections in patients with diabetes mellitus and hyperglucosuria.

DOI PubMed

A nationwide epidemiologic, clinical, genetic study of Usher syndrome in Japan

Hidekane Yoshimura, Shin ya Nishio, Yuichi Isaka, Toru Kurokawa, Shin ichi Usami, Katada Akihiro, Noriko Ogasawara, Tomoko Shintani, Yumiko Kobayashi, Hiroaki Sato, Seiji Kakehata, Daisuke Kikuchi, Tetsuo Ikezono, Kotaro Ishikawa, Kyoko Shirai, Masahiro Takahashi, Satoshi Iwasaki, Yasuhiro Arai, Hajime Sano, Mayuri Okami, Hiroshi Nakanishi, Tomoko Esaki, Michihiko Sone, Jun Nakayama, Takayuki Okano, Yumi Ota, Hiroshi Nishimura, Yasushi Naito, Yuko Kataoka, Akiko Sugaya, Yukihide Maeda, Shin Masuda, Kazuma Sugawara, Hiroshi Yamashita, Naoto Hato, Takashi Nakagawa, Akira Ganaha, Tetsuya Tono, Ikuyo Miyanohara, Mikio Suzuki

Acta Oto-Laryngologica 141 ( 9 ) 841 - 846 2021

Background: Usher syndrome (USH) typically leads to deaf-blindness, requiring the provision of extensive education and rehabilitation services. Therefore, investigating the prevalence is crucial to requests for proper government support for USH patients. Objective: The aim was to perform a nationwide epidemiologic survey of USH in Japan to estimate the prevalence of USH and reveal the relative frequency and characteristics of the three USH subtypes. Methods: To estimate the number of USH patients visiting hospitals over a 1-year period, 1,628 hospitals were randomly selected from all Departments of Otorhinolaryngology and Ophthalmology in Japan. Subsequently, we collected data regarding the clinical characteristics of each patient treated and the results of genetic testing, if performed. Results: We found that the prevalence of USH was at least 0.4 per 100,000 population. The frequency of clinical subtypes and causal genes for USH were consistent with previous reports. Also, we demonstrated the feasibility of genetic counseling for USH patients based on the results of genetic testing. Conclusion: USH is a rare disease, but requires social support due to the severity of symptoms. To minimize these issues, understanding the clinical characteristics and performing comprehensive genetic testing could allow early and accurate diagnosis as well as medical intervention.

DOI PubMed

The Prevalence and Clinical Characteristics of TECTA-Associated Autosomal Dominant Hearing Loss.

Rika Yasukawa, Hideaki Moteki, Shin-Ya Nishio, Kotaro Ishikawa, Satoko Abe, Yohei Honkura, Misako Hyogo, Ryota Mihashi, Tetsuo Ikezono, Tomoko Shintani, Noriko Ogasawara, Kyoko Shirai, Hiroshi Yoshihashi, Takashi Ishino, Koshi Otsuki, Tsukasa Ito, Kazuma Sugahara, Shin-Ichi Usami

Genes 10 ( 10 ) 2019.09 [Refereed] [International journal]

TECTA is well known as a causative gene for autosomal dominant mid-frequency hearing loss observed in various populations. In this study, we performed next-generation sequencing analysis of a large Japanese hearing loss cohort, including eight hundred and twelve (812) subjects from unrelated autosomal dominant hearing loss families, to estimate the prevalence and phenotype-genotype correlations in patients with TECTA mutations. The prevalence of TECTA mutations in Japanese autosomal dominant sensorineural hearing loss families was found to be 3.2%. With regard to the type of hearing loss, the patients with mutations in the nidogen-like domain or ZA domain of TECTA showed varied audiograms. However, most of the patients with mutations in the ZP domain showed mid-frequency hearing loss. The rate of hearing deterioration in TECTA-associated hearing loss patients and in the normal hearing Japanese control population were the same and regression lines for each group were parallel. We carried out haplotype analysis for four families which had one recurring missense variant, c.5597C>T (p.Thr1866Met). Our results revealed four different haplotypes, suggesting that this mutation occurred independently in each family. In conclusion, TECTA variants represent the second largest cause of autosomal dominant sensorineural hearing loss in Japan. The hearing loss progression observed in the patients with TECTA mutations might reflect presbycusis. The c.5597C>T mutation occurred in a mutational hot spot and is observed in many ethnic populations.

DOI PubMed

Cutting Edge: A Critical Role of Lesional T Follicular Helper Cells in the Pathogenesis of IgG4-Related Disease.

Ryuta Kamekura, Kenichi Takano, Motohisa Yamamoto, Koji Kawata, Katsunori Shigehara, Sumito Jitsukawa, Tomonori Nagaya, Fumie Ito, Akinori Sato, Noriko Ogasawara, Chieko Tsubomatsu, Hiroki Takahashi, Hiroshi Nakase, Tetsuo Himi, Shingo Ichimiya

Journal of immunology (Baltimore, Md. : 1950) ( AMER ASSOC IMMUNOLOGISTS ) 199 ( 8 ) 2624 - 2629 2017.10 [Refereed] [International journal]

IgG4-related disease (IgG4-RD) is a newly recognized systemic chronic fibroinflammatory disease. However, the pathogenesis of IgG4-RD remains unknown. To determine the pathophysiologic features of IgG4-RD, we examined T follicular helper (Tfh) cells in lesions and blood from patients with IgG4-RD. Patients with IgG4-related dacryoadenitis and sialadenitis (IgG4-DS) showed increased infiltration of Tfh cells highly expressing programmed death 1 and ICOS in submandibular glands. Tfh cells from IgG4-DS submandibular glands had higher expression of B cell lymphoma 6 and a greater capacity to help B cells produce IgG4 than did tonsillar Tfh cells. We also found that the percentage of programmed death 1hi circulating Tfh cells in IgG4-DS patients was higher than that in healthy volunteers and was well correlated with clinical parameters. Our findings indicate that anomalous Tfh cells in tissue lesions of IgG4-RD have features distinct from those in lymphoid counterparts or blood and potentially regulate local IgG4 production in IgG4-RD.

DOI PubMed

Regulation of claudin-4 via p63 in human epithelial cells.

Takashi Kojima, Takayuki Kohno, Terufumi Kubo, Yakuto Kaneko, Takuya Kakuki, Akito Kakiuchi, Makoto Kurose, Ken-Ichi Takano, Noriko Ogasawara, Kazufumi Obata, Kazuaki Nomura, Ryo Miyata, Takumi Konno, Shingo Ichimiya, Tetsuo Himi

Annals of the New York Academy of Sciences ( WILEY ) 1405 ( 1 ) 25 - 31 2017.10 [Refereed] [International journal]

P63 is a regulator of cell-cell junction complexes in the epidermis. Claudin-4 is regulated via various factors in normal epithelial cells and diseases. We found that claudin-4 was directly regulated via p63 (TAp63 and ΔNp63) in human keratinocytes and nasal epithelial cells. In the epidermis of atopic dermatitis (AD), which contains ΔNp63-deficient keratinocytes, high expression of claudin-4 was observed. In primary keratinocytes, downregulation of ΔNp63 by treatment with short interfering RNA (siRNA)-p63 induced claudin-4 expression. In nasal epithelial cells in the context of rhinitis or nasal polyps, upregulation of TAp63 and downregulation of claudin-4 were observed. In primary nasal epithelial cells transfected with the human telomerase reverse transcriptase gene, knockdown of p63 by siRNAs induced claudin-4 expression. Taken together, these findings indicate that p63 is a negative regulator of claudin-4 expression. Understanding the regulation of claudin-4 via p63 in human epithelial cells may be important for developing therapies for allergies and drug delivery systems.

DOI PubMed

The role of transcriptional factor p63 in regulation of epithelial barrier and ciliogenesis of human nasal epithelial cells.

Yakuto Kaneko, Takayuki Kohno, Takuya Kakuki, Ken-Ichi Takano, Noriko Ogasawara, Ryo Miyata, Shin Kikuchi, Takumi Konno, Tsuyoshi Ohkuni, Ryoto Yajima, Akito Kakiuchi, Shin-Ichi Yokota, Tetsuo Himi, Takashi Kojima

Scientific reports ( NATURE PUBLISHING GROUP ) 7 ( 1 ) 10935 - 10935 2017.09 [Refereed] [International journal]

Disruption of nasal epithelial tight junctions (TJs) and ciliary dysfunction are found in patients with chronic rhinosinusitis (CRS) and nasal polyps (NPs), along with an increase of p63-positive basal cells and histone deacetylase (HDAC) activity. To investigate these mechanisms, primary cultures of HNECs transfected with human telomerase reverse transcriptase (hTERT-HNECs) were transfected with siRNAs of TAp63 and ΔNp63, treated with the NF-kB inhibitor curucumin and inhibitors of HDACs, and infected with respiratory syncytial virus (RSV). In TERT-HNECs, knockdown of p63 by siRNAs of TAp63 and ΔNp63, induced claudin-1 and -4 with Sp1 activity and enhanced barrier and fence functions. The knockdown of p63 enhanced the number of microvilli with the presence of cilia-like structures. Treatment with curcumin and inhibitors of HDACs, or infection with RSV prevented expression of p63 with an increase of claudin-4 and the number of microvilli. The knockdown or downregulation of p63 inhibited phospho-p38MAPK, and the p38MAPK inhibitor downregulated p63 and upregulated the barrier function. Thus, epithelial barrier and ciliogenesis of nasal epithelium are regulated in a p63-negative manner in normal and upper airway diseases. Understanding of the regulation of p63/p38 MAPK/NF-κB may be important in the therapy for airway allergy and its drug delivery system.

DOI PubMed

Chorda tympani nerve dysfunction associated with congenital microtia.

Kenichi Takano, Nozomi Takahashi, Noriko Ogasawara, Takatoshi Yotsuyanagi, Tetsuo Himi

Acta oto-laryngologica ( TAYLOR & FRANCIS LTD ) 137 ( 7 ) 686 - 689 2017.07 [Refereed] [International journal]

CONCLUSION: This is the first report to investigate the correlation between ear anomalies related to the development of specific ear structures and chorda tympani dysfunction (CTD) in congenital microtia. CTD is not always consistent with the severity of the ear anomaly or the presence of facial nerve paralysis (FNP). OBJECTIVES: To investigate the relationship between the severity of ear anomalies and CTD as well as FNP in congenital microtia. METHODS: A retrospective assessment was performed for all patients with microtia over the period 2010-2016. All ears were graded based on the severity of ear deformity using the Jahrsdoerfer system, based on findings on computed tomography of the temporal bone. Electrogustometry (EGM) was performed to evaluate CTD. RESULTS: The group included 110 male and 62 female patients. The right ear was the most commonly affected (right 106, left 47). Eighteen patients (10.5%) had abnormal EGM thresholds. The mean (± SD) Jahrsdoerfer scores in the without CTD and positive for CTD groups were 6.53 ± 0.32 and 7.06 ± 0.37, respectively. In terms of sub-total points, there was no significant correlation between anatomic structure and CTD. There was no significant correlation between CTD and the presence of FNP.

DOI PubMed

Tigecycline Nonsusceptibility Occurs Exclusively in Fluoroquinolone-Resistant Escherichia coli Clinical Isolates, Including the Major Multidrug-Resistant Lineages O25b:H4-ST131-H30R and O1-ST648.

Toyotaka Sato, Yuuki Suzuki, Tsukasa Shiraishi, Hiroyuki Honda, Masaaki Shinagawa, Soh Yamamoto, Noriko Ogasawara, Hiroki Takahashi, Satoshi Takahashi, Yutaka Tamura, Shin-Ichi Yokota

Antimicrobial agents and chemotherapy ( AMER SOC MICROBIOLOGY ) 61 ( 2 ) 2017.02 [Refereed] [International journal]

Tigecycline (TGC) is a last-line drug for multidrug-resistant Enterobacteriaceae We investigated the mechanism(s) underlying TGC nonsusceptibility (TGC resistant/intermediate) in Escherichia coli clinical isolates. The MIC of TGC was determined for 277 fluoroquinolone-susceptible isolates (ciprofloxacin [CIP] MIC, <0.125 mg/liter) and 194 fluoroquinolone-resistant isolates (CIP MIC, >2 mg/liter). The MIC50 and MIC90 for TGC in fluoroquinolone-resistant isolates were 2-fold higher than those in fluoroquinolone-susceptible isolates (MIC50, 0.5 mg/liter versus 0.25 mg/liter; MIC90, 1 mg/liter versus 0.5 mg/liter, respectively). Two fluoroquinolone-resistant isolates (O25b:H4-ST131-H30R and O125:H37-ST48) were TGC resistant (MICs of 4 and 16 mg/liter, respectively), and four other isolates of O25b:H4-ST131-H30R and an isolate of O1-ST648 showed an intermediate interpretation (MIC, 2 mg/liter). No TGC-resistant/intermediate strains were found among the fluoroquinolone-susceptible isolates. The TGC-resistant/intermediate isolates expressed higher levels of acrA and acrB and had lower intracellular TGC concentrations than susceptible isolates, and they possessed mutations in acrR and/or marR The MICs of acrAB-deficient mutants were markedly lower (0.25 mg/liter) than those of the parental strain. After continuous stepwise exposure to CIP in vitro, six of eight TGC-susceptible isolates had reduced TGC susceptibility. Two of them acquired TGC resistance (TGC MIC, 4 mg/liter) and exhibited expression of acrA and acrB and mutations in acrR and/or marR In conclusion, a population of fluoroquinolone-resistant E. coli isolates, including major extraintestinal pathogenic lineages O25b:H4-ST131-H30R and O1-ST648, showed reduced susceptibility to TGC due to overexpression of the efflux pump AcrAB-TolC, leading to decreased intracellular concentrations of the antibiotics that may be associated with the development of fluoroquinolone resistance.

DOI PubMed

HIV-associated cystic lesions of the parotid gland

Noriko Ogasawara, Ken-ichi Takano, Hajime Kobayashi, Keisuke Kikuchi, Hiroshi Matsumiya, Iwao Yoshioka, Tetsuo Himi

AURIS NASUS LARYNX ( ELSEVIER SCI LTD ) 44 ( 1 ) 126 - 130 2017.02 [Refereed]

We present two cases of an HIV-associated parotid gland cyst. One case was a 36-year-old HIV infected woman. She was diagnosed with HIV infection and presented with slowly enlarged parotid gland cysts together with elevation of HIV viral RNA copies/mL in her serum. She was performed parotid gland biopsy under the general anesthesia. The histopathologic analysis revealed negative HIV p24-antigen in her parotid gland tissue. The other case was a 43-year-old man found his parotid gland swelling shortly after highly active antiretroviral therapy (HAART). He was diagnosed with HIV infection 2 years previously. He had started HAART several days before. He showed exceeding elevation of IgE in his serum. We treated him with medication using anti-histamic drugs for his cyst. A computed tomography scan revealed a complete response of his parotid gland cyst 4 weeks after the medication. His serum IgE level was decreased to half of the level before the medication. These findings suggested that the parotid gland swelling associated with HIV was due to various factors including immune reconstitution inflammatory syndrome (IRIS). In case such a parotid gland swelling, we could avoid invasive treatments. (C)2016 Elsevier Ireland Ltd. All rights reserved.

DOI PubMed

Lipid mediators foster the differentiation of T follicular helper cells.

Tomonori Nagaya, Koji Kawata, Ryuta Kamekura, Sumito Jitsukawa, Terufumi Kubo, Motonari Kamei, Noriko Ogasawara, Ken-Ichi Takano, Tetsuo Himi, Shingo Ichimiya

Immunology letters ( ELSEVIER SCIENCE BV ) 181 51 - 57 2017.01 [Refereed] [International journal]

Lipid mediators such as leukotrienes and lipoxines broadly regulate innate and acquired immunity, and their dysfunction causes various immune-mediated disorders. We previously reported a salient feature of arachidonate 5-lipoxyganase (Alox5), which is responsible for the production of such lipid mediators, in the regulation of high affinity antibodies in vivo. The aim of this study was to determine the functional significance of Alox5-related lipid mediators during the processes of acquired humoral responses. The results of in vitro experiments using lymphocytes in tonsils and blood specimens showed that lipoxin A4 (LXA4) and leukotriene B4 (LTB4) have the capacity to differentiate naïve CD4+ T cells into T follicular helper (Tfh) cells, which activate naïve B cells to form germinal centers. Such a function of LXA4 was further supported by results of in vitro studies using BML-111 and BOC-2, which are an agonist and an antagonist, respectively, of FPR2 of an LXA4-specific cell-surface receptor. The results suggest that such lipid mediators have a potential role in the development of lymphoid follicles through the regulation of Tfh cell differentiation.

DOI PubMed

Mechanism of Reduced Susceptibility to Fosfomycin in Escherichia coli Clinical Isolates.

Yasuo Ohkoshi, Toyotaka Sato, Yuuki Suzuki, Soh Yamamoto, Tsukasa Shiraishi, Noriko Ogasawara, Shin-Ichi Yokota

BioMed research international ( HINDAWI LTD ) 2017 5470241 - 5470241 2017 [Refereed] [International journal]

In recent years, multidrug resistance of Escherichia coli has become a serious problem. However, resistance to fosfomycin (FOM) has been low. We screened E. coli clinical isolates with reduced susceptibility to FOM and characterized molecular mechanisms of resistance and reduced susceptibility of these strains. Ten strains showing reduced FOM susceptibility (MIC ≥ 8 μg/mL) in 211 clinical isolates were found and examined. Acquisition of genes encoding FOM-modifying enzyme genes (fos genes) and mutations in murA that underlie high resistance to FOM were not observed. We examined ability of FOM incorporation via glucose-6-phosphate (G6P) transporter and sn-glycerol-3-phosphate transporter. In ten strains, nine showed lack of growth on M9 minimum salt agar supplemented with G6P. Eight of the ten strains showed fluctuated induction by G6P of uhpT that encodes G6P transporter expression. Nucleotide sequences of the uhpT, uhpA, glpT, ptsI, and cyaA shared several deletions and amino acid mutations in the nine strains with lack of growth on G6P-supplemented M9 agar. In conclusion, reduction of uhpT function is largely responsible for the reduced sensitivity to FOM in clinical isolates that have not acquired FOM-modifying genes or mutations in murA. However, there are a few strains whose mechanisms of reduced susceptibility to FOM are still unclear.

DOI PubMed

Pathogenic Lineage of mcr-Negative Colistin-Resistant Escherichia coli, Japan, 2008-2015.

Toyotaka Sato, Akira Fukuda, Yuuki Suzuki, Tsukasa Shiraishi, Hiroyuki Honda, Masaaki Shinagawa, Soh Yamamoto, Noriko Ogasawara, Masaru Usui, Hiroki Takahashi, Satoshi Takahashi, Yutaka Tamura, Shin-Ichi Yokota

Emerging infectious diseases ( CENTERS DISEASE CONTROL ) 22 ( 12 ) 2223 - 2225 2016.12 [Refereed] [International journal]

DOI PubMed

Outcomes of visually impaired patients who received cochlear implantations.

Kenichi Takano, Aya Kaizaki, Etsuko Saikawa, Ayami Konno, Noriko Ogasawara, Tetsuo Himi

Nihon Jibiinkoka Gakkai kaiho ( Oto-Rhino-Laryngological Society of Japan Inc. ) 119 ( 12 ) 1551 - 2 2016.12 [Refereed] [Domestic journal]

DOI PubMed

The Association of External and Middle Ear Anomaly and Mandibular Morphology in Congenital Microtia

Kenichi Takano, Nozomi Takahashi, Noriko Ogasawara, Tetsuo Himi

OTOLOGY & NEUROTOLOGY ( LIPPINCOTT WILLIAMS & WILKINS ) 37 ( 7 ) 889 - 894 2016.08 [Refereed]

Objective: To investigate the relationship between the severity of ear anomaly and mandibular dysplasia in congenital microtia. Study Design: Retrospective case review. Setting: Sapporo Medical University Hospital. Patients: Congenital microtia: 44 patients over a period of 4 years. Interventions: The height of the condylar process of the mandible was assessed by three-dimensional computed tomography (CT), and the patients were divided into three groups based on the ratio of the condylar process height on the affected side to that on the unaffected side: Group A, >= 1.00; Group B, 0.99 to 0.85; Group C, <0.85. Developmental abnormalities of the ear were evaluated using Jahrsdoerfer's scoring system on high-resolution CT scans. Main Outcome Measures: Nonparametric statistical tests were used to determine correlations between the height of the condylar process of the mandible and Jahrsdoerfer's score. Results: The total Jahrsdoerfer's score for each group was 7.36 +/- 2.23, 7.28 +/- 0.10, and 4.52 +/- 0.30, respectively; this value was significantly lower in Group C than in the other groups. In terms of subtotal points, oval window open, middle ear aeration, and mastoid pneumatization correlated significantly with mandibular dysplasia. Patients in Group C tended to have grade III microtia, by Marx's classification. Facial nerve weakness was not significantly correlated with mandibular dysplasia. Conclusions: In congenital microtia, mandibular development correlated significantly with aeration of the middle ear space, pneumatization of the mastoid, and formation of the oval window, but not with the presence of a bony part of the external auditory canal or with ossicular development.

DOI PubMed

Bob1 limits cellular frequency of T-follicular helper cells (vol 46, pg 1361, 2016)

Yamashita Keiji, Kawata Koji, Matsumiya Hiroshi, Kamekura Ryuta, Jitsukawa Sumito, Nagaya Tomonori, Ogasawara Noriko, Takano Ken-ichi, Kubo Terufumi, Kimura Sachiko, Shigehara Katsunori, Himi Tetsuo, Ichimiya Shingo

EUROPEAN JOURNAL OF IMMUNOLOGY 46 ( 8 ) 2054 2016.08 [Refereed]

Measles Virus Genotype D Wild Strains Suppress Interferon-Stimulated Gene Expression More Potently than Laboratory Strains in SiHa Cells

Masaru Jinushi, Soh Yamamoto, Noriko Ogasawara, Hideki Nagano, Shin Hashimoto, Hiroyuki Tsutsumi, Tetsuo Himi, Shin-ichi Yokota

VIRAL IMMUNOLOGY ( MARY ANN LIEBERT, INC ) 29 ( 5 ) 296 - 306 2016.06 [Refereed]

Changes in interferon (IFN)-stimulated gene (ISG) expression in cells infected with measles virus (MeV), four wild strains (belonging to different genotypes), and the laboratory strain Edmonston were examined. ISGs [MxA, 2'-5'-oligoadenylate synthetase, and interferon regulatory factor-1] were upregulated in an MeV-infection- induced manner and in an IFN-induced manner. In MeV-infected SiHa cell lines, the MeV infection-induced expression levels were in the order of A>H1>D8>D5>D3. On the other hand, all infected cell lines abolished type I and III IFN-induced ISG expression. However, partial type II IFN-mediated induction was observed in the MeV-infected cells. The wild strain of genotype D3 was the most potent inhibitor of MeV infection-induced and IFN-induced ISG expression and generated the highest titer of infectious viral particles. Edmonston triggered the highest levels of MeV infection-induced ISG expression in SiHa cells and produced the lowest titer of infectious particles. Expression of the viral C protein was associated with suppression of MeV infection-induced and type II IFN-induced ISG expression.

DOI PubMed

Bob1 limits cellular frequency of T-follicular helper cells

Keiji Yamashita, Koji Kawata, Hiroshi Matsumiya, Ryuta Kamekura, Sumito Jitsukawa, Tomonori Nagaya, Noriko Ogasawara, Ken-ichi Takano, Terufumi Kubo, Sachiko Kimura, Katsunori Shigehara, Tetsuo Himi, Shingo Ichimiya

EUROPEAN JOURNAL OF IMMUNOLOGY ( WILEY ) 46 ( 6 ) 1361 - 1370 2016.06 [Refereed]

T follicular helper (Tfh) cells are involved in specific humoral immunity at initial and recall phases. The fact that the transcription repressors B-cell lymphoma-6 and Blimp-1 determine lineages of Tfh cells and other types of effector CD4(+) T cells, respectively, suggests that there are unique mechanisms to establish Tfh-cell identity. In this study, we found that Tfh cells preferentially express the transcriptional coactivator Bob1. Bob1 of Tfh cells was dispensable for the expression of B-cell lymphoma-6 and the functional property of the cells for B cell help. However, upon initial immunization of foreign antigens, the percentages of Tfh cells in Bob1(-/-) mice were much higher than those inwild-type (WT) mice. In addition, expansion of Tfh cells within Bob1(-/-)CD4(+) T cells transferred into WT mice revealed that the high frequency of Tfh cells was caused by a T-cell-intrinsic mechanism. These findings were further supported by the results of in vitro studies demonstrating that Bob1(-/-) Tfh cells had greater proliferative activity in response to stimuli by CD3/CD28 monoclonal antibody and were also refractory to CD3-induced cell death in comparison to WT Tfh cells. These results suggest that Tfh cells harbor a Bob1-related mechanism to restrict numerical frequency against stimulation of TCRs.

DOI PubMed

Outcomes of visually impaired patients who received cochlear implantations

Kenichi Takano, Aya Kaizaki, Etsuko Saikawa, Ayami Konnno, Noriko Ogasawara, Tetsuo Himi

AURIS NASUS LARYNX ( ELSEVIER SCI LTD ) 43 ( 3 ) 242 - 246 2016.06 [Refereed]

Objective: Patients with multiple sensory deficits, including hearing loss and visual impairment, present a unique problem. We evaluated the clinical outcomes of cochlear implantation in patients with severe to profound sensorineural hearing loss and visual impairment. Methods: We retrospectively reviewed eight patients with severe sensorineural hearing loss and visual impairment who underwent cochlear implantation at our institution between 1993 and 2014. The follow-up period was between 2 and 20 years. We evaluated the case histories, etiologies of hearing loss and visual impairment, pre- and postoperative pure-tone thresholds, speech perception rates after CI using the Japanese CD speech discrimination scoring system (CI-2004 test) for words and sentences, and pre- and postoperative communication means. Postoperative speech discrimination scores were compared between patients with and without visual impairment who underwent cochlear implantation. Results: The outcomes of cochlear implantation were good in all patients, with seven showing the ability to hold a conversation with others. The average proportion of correct answers for words and sentences in the CI-2004 test was 72.3 +/- 19.1% and 86.0 +/- 16.1%, respectively, for the patients with visual impairment and 62.1 +/- 21.7% and 78.5 +/- 20.9%, respectively, for those without visual impairment (based on auditory senses only). There were no significant differences in results between the patients with and without visual impairment. Conclusions: Cochlear implantation is important for the rehabilitation of patients with severe auditory loss and visual impairment. Medical staff members require additional skills to perform auditory evaluations and rehabilitate patients with multiple sensory deficits. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

DOI PubMed

A novel nonsense mutation in the NOG gene causes familial NOG-related symphalangism spectrum disorder.

Kenichi Takano, Noriko Ogasawara, Tatsuo Matsunaga, Hideki Mutai, Akihiro Sakurai, Aki Ishikawa, Tetsuo Himi

Human genome variation 3 16023 - 16023 2016 [Refereed] [International journal]

The human noggin (NOG) gene is responsible for a broad spectrum of clinical manifestations of NOG-related symphalangism spectrum disorder (NOG-SSD), which include proximal symphalangism, multiple synostoses, stapes ankylosis with broad thumbs (SABTT), tarsal-carpal coalition syndrome, and brachydactyly type B2. Some of these disorders exhibit phenotypes associated with congenital stapes ankylosis. In the present study, we describe a Japanese pedigree with dactylosymphysis and conductive hearing loss due to congenital stapes ankylosis. The range of motion in her elbow joint was also restricted. The family showed multiple clinical features and was diagnosed with SABTT. Sanger sequencing analysis of the NOG gene in the family members revealed a novel heterozygous nonsense mutation (c.397A>T; p.K133*). In the family, the prevalence of dactylosymphysis and hyperopia was 100% while that of stapes ankylosis was less than 100%. Stapes surgery using a CO2 laser led to a significant improvement of the conductive hearing loss. This novel mutation expands our understanding of NOG-SSD from clinical and genetic perspectives.

DOI PubMed

Accessory parotid gland tumors: A series of 4 cases

Takuya Kakuki, Kenichi Takano, Makoto Kurose, Atsushi Kondo, Tsuyoshi Okuni, Noriko Ogasawara, Tetsuo Himi

Ear, Nose and Throat Journal ( Medquest Communications LLC ) 95 ( 7 ) E35 - 8 2016 [Refereed]

Accessory parotid gland tumors are clinically rare, and their management remains unclear. In this article, we describe our experience with 4 patients-2 males and 2 females, aged 13 to 66 years-who were diagnosed with an accessory parotid gland tumor. All patients presented with an asymptomatic midcheek swelling, and all underwent fine-needle aspiration biopsy, ultrasonography, computed tomography, and magnetic resonance imaging. A standard parotidectomy was performed on all patients. Postoperatively, 2 patients were found to have a malignant tumor, while the other 2 had a pleomorphic adenoma. No patient experienced any obvious facial nerve injuries postoperatively, and no recurrences were observed. We discuss the preoperative evaluation, treatment, and prognosis of these tumors, and we briefly describe the literature. The first choice of treatment for accessory parotid gland tumors is surgical resection. In our experience, a standard parotidectomy approach is safe and cosmetically appealing.

PubMed

Congenital microtia treated at Sapporo Medical University Hospital: Clinical characteristics and associated anomalies

Noriko Ogasawara, Sumito Jitsukawa, Nozomi Takahashi, Kenichi Takano, Tetsuo Himi

Advances in Oto-Rhino-Laryngology ( S. Karger AG ) 77 12 - 16 2016 [Refereed]

Seventy-three children who underwent plastic surgery for their external ear malformations between December 2010 and May 2013 at the Sapporo Medical University Hospital were evaluated. The predominance of right-sided malformation (62%) in males (71%) was similar to that reported previously, but the number of bilateral cases (9.3%) was lower than that in previous reports. We classified patients' ears using Marx's classification. The pure-tone average (average air conduction thresholds measured at 500, 1,000 and 2,000 Hz) was used as the representative value for the hearing level, which was compared with a patient's Marx classification. We evaluated the facial nerve position using high-resolution computed tomography scans. A thorough understanding of anatomical variations and complications, as well as performing appropriate treatments, is required for otolaryngologists to effectively manage congenital microtia.

DOI PubMed

Clinical review of cochlear implantation performed at sapporo medical university hospital

Noriko Ogasawara, Kenichi Takano, Tomoko Shintani, Etsuko Saikawa, Nozomi Takahashi, Fumie Ito, Tetsuo Himi

Advances in Oto-Rhino-Laryngology ( S. Karger AG ) 77 1 - 6 2016 [Refereed]

More than 20 years have passed since cochlear implantation (CI) was first introduced in Japan. We began CI at the Sapporo Medical University Hospital in 1988 since then, up to the first half of 2015, we have performed CI on 280 ears. In patients aged less than and those aged over 18 years, 121 and 159 ears, respectively, have undergone surgery. This report presents typical cases of CI, such as an adult case, a bilateral case, a case where both hearing and vision were impaired, a pediatric case, a case with multiple handicaps, a case with a genetic mutation leading to severe hearing loss, and a complicated case. In addition, complications with CI cases experienced during extended follow-up periods are also summarized.

DOI PubMed

Relationship between otitis media and epithelial function in the lymphoepithelium of pediatric adenoids

Noriko Ogasawara, Keisuke Yamamoto, Kenichi Takano, Tetsuo Himi

Advances in Oto-Rhino-Laryngology ( S. Karger AG ) 77 33 - 39 2016 [Refereed]

Nose- or nasopharynx-associated lymphoid tissue (NALT) has a unique role that is distinct from that of other lymphoid tissues. During upper airway mucosal immune response, NALT induces a variety of responses, including cytokine and chemokine production and innate immune response, to establish acquired immunity. NALT consists of epithelial cells, epithelium-associated lymphoid tissues such as IgA-committed B cells, innate lymphocytes, T helper cells and dendritic cells. Intranasal immunization has recently been shown to effectively induce a proactive immune response in the local mucosa in addition to a systemic immune response. A variety of factors can cause otitis media, including Eustachian tube dysfunction, inflammation, allergy and viral and bacterial infections. However, the detailed pathogenesis of otitis media is not yet completely understood. In this report, we provide evidence suggesting that adenoid tissue as a component of NALT in children may play an important role in inducing innate immunity following viral infection.

DOI PubMed

Cochlear implantation in children with cochlear malformation

Etsuko Saikawa, Kenichi Takano, Noriko Ogasawara, Chieko Tsubomatsu, Nozomi Takahashi, Hideaki Shirasaki, Tetsuo Himi

Advances in Oto-Rhino-Laryngology ( S. Karger AG ) 77 7 - 11 2016 [Refereed]

Cochlear implantation (CI) has proven to be an effective treatment for severe bilateral sensorineural hearing loss (SNHL). Inner ear malformation is a rare anomaly and occurs in approximately 20% of cases with congenital SNHL. In cases with cochlear malformation, CI can be successfully performed in nearly all patients, the exceptions being those with complete labyrinthine and cochlear aplasia. It is important to evaluate the severity of inner ear deformity and other associated anomalies during the preimplantation radiological assessment in order to identify any complication that may potentially occur during the surgery and subsequent patient management.

DOI PubMed

Mumps Virus Induces Protein-Kinase-R-Dependent Stress Granules, Partly Suppressing Type III Interferon Production.

Shin Hashimoto, Soh Yamamoto, Noriko Ogasawara, Toyotaka Sato, Keisuke Yamamoto, Hiroshi Katoh, Toru Kubota, Tsukasa Shiraishi, Takashi Kojima, Tetsuo Himi, Hiroyuki Tsutsumi, Shin-Ichi Yokota

PloS one ( PUBLIC LIBRARY SCIENCE ) 11 ( 8 ) e0161793 2016 [Refereed] [International journal]

Stress granules (SGs) are cytoplasmic granular aggregations that are induced by cellular stress, including viral infection. SGs have opposing antiviral and proviral roles, which depend on virus species. The exact function of SGs during viral infection is not fully understood. Here, we showed that mumps virus (MuV) induced SGs depending on activation of protein kinase R (PKR). MuV infection strongly induced interferon (IFN)-λ1, 2 and 3, and IFN-β through activation of IFN regulatory factor 3 (IRF3) via retinoic acid inducible gene-I (RIG-I) and the mitochondrial antiviral signaling (MAVS) pathway. MuV-induced IFNs were strongly upregulated in PKR-knockdown cells. MuV-induced SG formation was suppressed by knockdown of PKR and SG marker proteins, Ras-GTPase-activating protein SH3-domain-binding protein 1 and T-cell-restricted intracellular antigen-1, and significantly increased the levels of MuV-induced IFN-λ1. However, viral titer was not altered by suppression of SG formation. PKR was required for induction of SGs by MuV infection and regulated type III IFN (IFN-λ1) mRNA stability. MuV-induced SGs partly suppressed type III IFN production by MuV; however, the limited suppression was not sufficient to inhibit MuV replication in cell culture. Our results provide insight into the relationship between SGs and IFN production induced by MuV infection.

DOI PubMed

Intrafamilial, Preferentially Mother-to-Child and Intraspousal, Helicobacter pylori Infection in Japan Determined by Mutilocus Sequence Typing and Random Amplified Polymorphic DNA Fingerprinting

Shin-ichi Yokota, Mutsuko Konno, Shin-ichi Fujiwara, Nariaki Toita, Michiko Takahashi, Soh Yamamoto, Noriko Ogasawara, Tsukasa Shiraishi

HELICOBACTER ( WILEY-BLACKWELL ) 20 ( 5 ) 334 - 342 2015.10 [Refereed]

Background: The infection route of Helicobacter pylori has been recognized to be mainly intrafamilial, preferentially mother-to-child, especially in developed countries. To determine the transmission route, we examined whether multilocus sequence typing (MLST) was useful for analysis of intrafamilial infection. The possibility of intraspousal infection was also evaluated. Materials and Methods: Clonal relationships between strains derived from 35 index Japanese pediatric patients, and their family members were analyzed by two genetic typing procedures, MLST and random amplified polymorphic DNA (RAPD) fingerprinting. Results: Mostly coincident results were obtained by MLST and RAPD. By MLST, the allele of loci in the isolates mostly matched between the index child and both the father and mother for 9 (25.7%) of the 35 patients, between the index child and the mother for 25 (60.0%) of the 35 patients. Conclusions: MLST is useful for analyzing the infection route of H. pylori as a highly reproducible method. Intrafamilial, especially mother-to-children and sibling, infection is the dominant transmission route. Intraspousal infection is also thought to occur in about a quarter in the Japanese families.

DOI PubMed

Poly(I:C) induced microRNA-146a regulates epithelial barrier and secretion of proinflammatory cytokines in human nasal epithelial cells

Ryo Miyata, Takuya Kakuki, Kazuaki Nomura, Tsuyoshi Ohkuni, Noriko Ogasawara, Ken-ichi Takano, Takumi Konno, Takayuki Kohno, Norimasa Sawada, Tetsuo Himi, Takashi Kojima

EUROPEAN JOURNAL OF PHARMACOLOGY ( ELSEVIER SCIENCE BV ) 761 375 - 382 2015.08 [Refereed]

Human nasal epithelial cells (HNECs) are important in the tight junctional barrier and innate immune defense protecting against pathogens invading via Toll-like receptors (TERs). MicroRNAs (miRNAs) I egulate expression of tight junctions as direct or indirect targeting genes and maintain the barrier Function. However, the roles of miRNAs in the epithelial barrier of HNECs via TLRs remain unknown. In the present study, to investigate the effects of miRNAs on the epithelial barrier of HNECs via TLRs, primary cultured HNECs transfected with human telomerase reverse transcriptase (hTERT-HNECs), were treated with the TLR3 ligand poly(I:C) and miRNA array analysis was performed. In the miRNA array of the cells treated with poly(I:C), upregulation of miR-187, -146a, -574, -4274, -4433, -4455 and -4750, and downregulation of miR-4785 by more than twofold compared to the control were observed. When control HNECs were treated with mimics and inhibitors of these miRNAs, an miR-146a mimic induced expression of tight junction proteins claudin-1, occludin and JAM-A together with an increase of the epithelial barrier function. The poly(I:C)-induced miR-146a was regulated via the distinct TLR3-mediatecl signal pathways PI3K, JNK and NE-kappa B. Furthermore, the miR-146a mimic prevented downregulation of claudin-1 and JAM-A and the secretion of proinflammatory cytokines IL-8 and TNF-alpha induced by poly (I:C) by targeting TRAFG. These findings indicate that, in HNECs, miRNA-146a plays crucial roles in maintenance of the tight junction barrier and innate immune defense protecting against invading pathogens. (C) 2015 Elsevier B.V. All rights reserved.

DOI PubMed

Vascular tumors of the external auditory canal: three case reports and a review of the literature

Keisuke Yamamoto, Noriko Ogasawara, Nobuhiko Seki, Nobuhiro Konno, Hiroshi Tsubota, Tetsuo Himi

SPRINGERPLUS ( SPRINGER INTERNATIONAL PUBLISHING AG ) 4 307 2015.07 [Refereed]

Background: Benign vascular tumors are frequently found in the head and neck, however, such tumors of the external auditory canal are extremely rare. We report three cases of benign vascular tumors limited to the external auditory canal. Case description: A 50-year-old woman was diagnosed during an episode of ear fullness and hearing loss. A 10-year-old boy consulted our department about an episode of recurrent otorrhagia. A 20-year-old man found a bulge of his external auditory canal by chance. Complete surgical resection was performed for the first patient. The second patient underwent electro-coagulation of the lesion. In the third patient, to exclude the possibility of a malignant tumor, a biopsy was performed under local anesthesia. Histopathological analysis demonstrated the characteristic of vascular tumors. The lesion showed remarkable reduction during his treatment with antibiotics and cleaning. He remains under careful observation. Discussion and evaluation: In diagnosis, there is sometimes confusion between vascular tumors and malformations. Generally, vascular malformations can be differentiated from vascular tumors since they are present at birth and are generally stable. Conclusion: Decision making about treatment of benign vascular tumors is sometimes confusing because of the difficulty in diagnosis. We performed biopsy for only one of our three cases because we regard that informal biopsy should not be conducted for lesions with difficult hemostic conditions and locations.

DOI PubMed

Alteration of circulating type 2 follicular helper T cells and regulatory B cells underlies the comorbid association of allergic rhinitis with bronchial asthma

Ryuta Karnekura, Katsunori Shigehara, Satsuki Miyajima, Sumito Jitsukawa, Koji Kawata, Keiji Yamashita, Tomonori Nagaya, Ayako Kumagai, Akinori Sato, Hiroshi Matsumiya, Noriko Ogasawara, Nobuhiko Seki, Kenichi Takano, Yasuo Kokai, Hiroki Takahashi, Tetsuo Himi, Shingo Ichimiya

CLINICAL IMMUNOLOGY ( ACADEMIC PRESS INC ELSEVIER SCIENCE ) 158 ( 2 ) 204 - 211 2015.06 [Refereed]

Allergic rhinitis (AR), the most common allergic disorder of the airway, is often accompanied by bronchial asthma. However, little is known about the mechanism by which AR advances to AR comorbid with bronchial asthma (AR + Asthma). To determine the pathophysiologic features of AR and AR + Asthma, we examined subsets of follicular helper T (Tfh) cells and regulatory B (Breg) cells in peripheral blood from AR and AR + Asthma patients. The results showed polarization of Tfh2 cells within Tfh cell subsets in both AR and AR + Asthma cases. Interestingly, the %Breg cells in total B cells were decreased in AR cases and, more extensively, in AR + Asthma cases. Moreover, we found significant correlations of fractional exhaled nitricoxide and blood eosinophil levels with the index %Tfh2 cells per %Breg cells. Our findings indicate that relative decrease in Breg cells under the condition of Tfh2 cell skewing is a putative exaggerating factor of AR to bronchial asthma. (C) 2015 The Authors. Published by Elsevier Inc.

DOI PubMed

当科における2歳未満の人工内耳埋込術症例の検討

高野賢一, 才川悦子, 小笠原徳子, 高橋希, 氷見徹夫

小児耳鼻咽喉科 ( 日本小児耳鼻咽喉科学会 ) 36 ( 2 ) 221 - 221 2015.04

アレルギー性気道疾患の病態形成における濾胞ヘルパーT細胞と制御性B細胞の役割

亀倉隆太, 重原克則, 實川純人, 小笠原徳子, 高野賢一, 氷見徹夫, 一宮慎吾

アレルギー ( (一社)日本アレルギー学会 ) 64 ( 3-4 ) 570 - 570 2015.04

当科における人工内耳埋め込み術の術後合併症に関する検討

小笠原徳子, 才川悦子, 高野賢一, 新谷朋子, 氷見徹夫

Otology Japan ( (一社)日本耳科学会 ) 25 ( 1 ) 51 - 57 2015.02

当科では1988年から人工内耳埋め込み術を行っている。導入から25年以上が経過し、これまでに経験した術後合併症についてその原因と対策を検討することを目的として後ろ向き調査を行った。1988年から2013年5月までに札幌医科大学病院耳鼻咽喉科にて人工内耳埋め込み術を施行した248耳を調査対象とした。術後合併症を「人工内耳埋め込み術後に何らかの追加の診療・治療・処置を必要とした症状」と定義し、診療録からの記載をもとに検討した。結果として248耳中、92耳(37%)に何らかの術後合併症を認めた。観血的治療を必要とした重度合併症は12耳(4%)であった。人工内耳機器は時代により変遷しており、手術方法、適応基準、適応年齢に変化が生じてきている。これまでの報告と同様に、きめ細かな配慮を丁寧に行い、手術実施医療機関において長期の経過観察を行うことが合併症の減少につながると考えられた。(著者抄録)

当科における中等度難聴児の検討

今野綾美, 才川悦子, 新谷朋子, 小笠原徳子, 海崎文, 吉野真代, 北川可恵, 氷見徹夫

Audiology Japan ( (一社)日本聴覚医学会 ) 57 ( 5 ) 447 - 448 2014.10

3歳以降に診断をうけた中等度・高度難聴症例の検討

才川悦子, 新谷朋子, 小笠原徳子, 高橋希, 海崎文, 吉野真代, 今野綾美, 北川可恵, 氷見徹夫

Audiology Japan ( (一社)日本聴覚医学会 ) 57 ( 5 ) 445 - 446 2014.10

Cochlear implantation in a patient with Paget's disease

Kenichi Takano, Etsuko Saikawa, Noriko Ogasawara, Tetsuo Himi

AMERICAN JOURNAL OF OTOLARYNGOLOGY ( W B SAUNDERS CO-ELSEVIER INC ) 35 ( 3 ) 408 - 410 2014.05 [Refereed]

Paget's disease of the temporal bone can cause hearing loss that eventually develops into profound deafness. However, the treatment options for hearing loss associated with Paget's disease are limited. Thus far, only 3 cases of cochlear implantation in patients with Paget's disease have been reported. In this study, we describe a 62-year-old woman who underwent cochlear implantation for progressive bilateral sensorineural hearing loss. The patient gained useful open-set speech perception over a 5-year postoperative period. Cochlear implantation can be beneficial in patients with profound hearing loss associated with Paget's disease. (C) 2014 Elsevier Inc. All rights reserved.

DOI PubMed

A clinical study of stapes fixation

Kenichi Takano, Tsuyoshi Okuni, Noriko Ogasawara

Otolaryngology - Head and Neck Surgery (Japan) 86 ( 2 ) 171 - 177 2014.02

We analyzed the result of stapes surgery patients including otosclerosis (56 ears) and congenital foot plate ankylosis (15 ears) between 1999 and 2011 in our hospital. The success rates of hearing improvement according to the statement of Otological Society of Japan were 92.6% at otosclerosis and 92.0% at congenital foot plate ankylosis. One revision case of otosclerosis showed an extensive incus erosion during revision surgery. In mixed congenital auditory ossicular malformation with especially stapes footplate fixation, the preoperative diagnosis might be difficult and requiring unexpected procedures with a poor hearing outcome.

視聴覚障害者の人工内耳装用の現状

海﨑文, 新谷朋子, 才川悦子, 小笠原徳子, 吉野真代, 今野綾美, 北川可恵, 氷見徹夫

ＡＵＤＩＯＬＯＧＹＪＡＰＡＮ ( 一般社団法人日本聴覚医学会 ) 57 ( 5 ) 293 - 294 2014

DOI CiNii

当院で人工内耳手術を行った小児進行性難聴例の検討

髙橋希, 才川悦子, 新谷朋子, 小笠原徳子, 海﨑文, 吉野真代, 今野綾美, 北川可恵

ＡＵＤＩＯＬＯＧＹＪＡＰＡＮ ( 一般社団法人日本聴覚医学会 ) 57 ( 5 ) 283 - 284 2014

DOI CiNii

Humulone suppresses replication of respiratory syncytial virus and release of IL-8 and RANTES in normal human nasal epithelial cells

Jun Fuchimoto, Takashi Kojima, Tamaki Okabayashi, Tomoyuki Masaki, Noriko Ogasawara, Kazufumi Obata, Kazuaki Nomura, Satoshi Hirakawa, Naoyuki Kobayashi, Tatsuro Shigyo, Shin-ichi Yokota, Nobuhiro Fujii, Hiroyuki Tsutsumi, Tetsuo Himi, Norimasa Sawada

MEDICAL MOLECULAR MORPHOLOGY ( SPRINGER JAPAN KK ) 46 ( 4 ) 203 - 209 2013.12 [Refereed]

Respiratory syncytial virus (RSV) is the major infectious agent causing serious respiratory tract inflammation in infants and young children. However, an effective vaccine and anti-viral therapy for RSV infection have not yet been developed. Hop-derived bitter acids have potent pharmacological effects on inflammation. Therefore, we investigated the effects of humulone, which is the main constituent of hop bitter acids, on the replication of RSV and release of the proinflammatory cytokine IL-8 and chemokine RANTES in RSV-infected human nasal epithelial cells (HNECs). We found that humulone prevented the expression of RSV/G-protein, formation of virus filaments and release of IL-8 and RANTES in a dose-dependent manner in RSV-infected HNECs. These findings suggest that humulone has protective effects against the replication of RSV, the virus assembly and the inflammatory responses in HNECs and that it is a useful biological product for the prevention and therapy for RSV infection.

DOI PubMed

Regulation of Tight Junctions in Upper Airway Epithelium

Takashi Kojima, Mitsuru Go, Ken-ichi Takano, Makoto Kurose, Tsuyoshi Ohkuni, Jun-ichi Koizumi, Ryuta Kamekura, Noriko Ogasawara, Tomoyuki Masaki, Jun Fuchimoto, Kazufumi Obata, Satoshi Hirakawa, Kazuaki Nomura, Takashi Keira, Ryou Miyata, Nobuhiro Fujii, Hiroyuki Tsutsumi, Tetsuo Himi, Norimasa Sawada

BIOMED RESEARCH INTERNATIONAL ( HINDAWI PUBLISHING CORPORATION ) 2013 947072 2013 [Refereed]

The mucosal barrier of the upper respiratory tract including the nasal cavity, which is the first site of exposure to inhaled antigens, plays an important role in host defense in terms of innate immunity and is regulated in large part by tight junctions of epithelial cells. Tight junction molecules are expressed in both M cells and dendritic cells as well as epithelial cells of upper airway. Various antigens are sampled, transported, and released to lymphocytes through the cells in nasal mucosa while they maintain the integrity of the barrier. Expression of tight junction molecules and the barrier function in normal human nasal epithelial cells (HNECs) are affected by various stimuli including growth factor, TLR ligand, and cytokine. In addition, epithelial-derived thymic stromal lymphopoietin (TSLP), which is a master switch for allergic inflammatory diseases including allergic rhinitis, enhances the barrier function together with an increase of tight junction molecules in HNECs. Furthermore, respiratory syncytial virus infection in HNECs in vitro induces expression of tight junction molecules and the barrier function together with proinflammatory cytokine release.. is paper summarizes the recent progress in our understanding of the regulation of tight junctions in the upper airway epithelium under normal, allergic, and RSV-infected conditions.

DOI PubMed

Solitary fibrous tumor of the head and neck in a child: Case report and review of the literature

Ogasawara Noriko, Kikuchi Keisuke, Yoshioka Iwao, Yamashita Keiji, Himi Tetsuo

Journal of Pediatric Surgery Case Reports ( Elsevier Inc. ) 1 ( 8 ) 194 - 196 2013

DOI

Hop water extract inhibits double-stranded RNA-induced thymic stromal lymphopoietin release from human nasal epithelial cells

Jun Fuchimoto, Takashi Kojima, Naoyuki Kobayashi, Tsuyoshi Ohkuni, Noriko Ogasawara, Tomoyuki Masaki, Kazufumi Obata, Kazuaki Nomura, Atsushi Kondoh, Tatsuro Shigyo, Tetsuo Himi, Norimasa Sawada

AMERICAN JOURNAL OF RHINOLOGY & ALLERGY ( OCEAN SIDE PUBLICATIONS INC ) 26 ( 6 ) 433 - 438 2012.11 [Refereed]

Background: Thymic stromal lymphopoietin (TSLP) acts as a master switch for allergic inflammation and plays a key role in allergic diseases, including allergic rhinitis. Double-stranded RNA (dsRNA) recognized by Toll-like receptor 3 (TLR3) strongly activates TSLP release from human nasal epithelial cells (HNECs). Hop (Humulus lupulus L.) extracts have been shown to have potent pharmacologic effects on inflammation. Methods: To investigate whether a hop water extract (HWE) prevents TSLP release from HNECs, human telomerase reverse transcriptase (hTERT)-transfected HNECs, used as a model of normal HNECs, were pretreated with HWE before treatment with the TLR3 ligand Polyinosine-polycytidylic acid (poly[I:C]). Results: In the hTERT-transfected HNECs, treatment with HWE significantly reduced poly(I:C)-induced production and release of TSLP in a dose-dependent manner, as well as dexamethasone. Treatment with the protein kinase C (PKC) inhibitor GF109203X and NF-kappa B inhibitor IMD-0354 also reduced poly(I:C)-induced TSLP release from hTERT-transfected HNECs. Treatment with HWE efficiently prevented up-regulation of PKC activity by 12-O-tetradecanoyl phorbol-13-acetate but not NF-kappa B activity induced by IL-1 beta in hTERT-transfected HNECs. Conclusion: Our results clearly indicated that HWE inhibited dsRNA-induced production and release of TSLP via a PKC signal pathway in HNECs and it may have potent preventive effects against allergic rhinitis.

DOI PubMed

ヒト鼻粘膜上皮細胞を用いたcurcuminによるRSvirusの複製阻害およびタイト結合発現誘導のメカニズム解析

小幡和史, 小島隆, 正木智之, 渕本潤, 平川賢史, 野村一顕, 高澤啓, 小笠原徳子, 氷見徹夫, 澤田典均

日本病理学会会誌 ( (一社)日本病理学会 ) 101 ( 1 ) 280 - 280 2012.03

Altered expression of claudin-1, claudin-7, and tricellulin regardless of human papilloma virus infection in human tonsillar squamous cell carcinoma

Atsushi Kondoh, Ken-Ichi Takano, Takashi Kojima, Tsuyoshi Ohkuni, Ryuta Kamekura, Noriko Ogasawara, Mitsuru Go, Norimasa Sawada, Tetsuo Himi

ACTA OTO-LARYNGOLOGICA ( INFORMA HEALTHCARE ) 131 ( 8 ) 861 - 868 2011.08 [Refereed]

Conclusions: Altered expression of claudin-1, claudin-7, and tricellulin in early tonsillar squamous cell carcinoma (SCC) independent of human papilloma virus (HPV) infection may lead to tumor progression. Objectives: Integral tight junction proteins, the claudins and tricellulin, play a crucial role in all tissues. HPV is significantly associated with tonsillar SCC. We sought to determine the expression of claudin-1, claudin-7, and tricellulin in HPV-infected and HPV-free tonsillar SCC. Methods: Twenty-eight tonsillar SCCs were studied by immunohistochemical analysis and real-time reverse transcription polymerase chain reaction with in situ hybridization analysis. Results: Compared with normal tissues, claudin-1 was strongly expressed, whereas claudin-7 and tricellulin were weakly expressed or were absent in primary SCC and metastatic lymph nodes. Claudin-7 and tricellulin were markedly reduced at all stages of tumor development. In situ hybridization analysis showed no correlation between HPV infection and altered expression of the tight junction proteins.

DOI PubMed

A nuclear factor-kappa B signaling pathway via protein kinase C delta regulates replication of respiratory syncytial virus in polarized normal human nasal epithelial cells

Tomoyuki Masaki, Takashi Kojima, Tamaki Okabayashi, Noriko Ogasawara, Tsuyoshi Ohkuni, Kazufumi Obata, Akira Takasawa, Masaki Murata, Satoshi Tanaka, Satoshi Hirakawa, Jun Fuchimoto, Takafumi Ninomiya, Nobuhiro Fujii, Hiroyuki Tsutsumi, Tetsuo Himi, Norimasa Sawada

MOLECULAR BIOLOGY OF THE CELL ( AMER SOC CELL BIOLOGY ) 22 ( 13 ) 2144 - 2156 2011.07 [Refereed]

Respiratory syncytial virus (RSV) is the major cause of bronchitis, asthma, and severe lower respiratory tract disease in infants and young children. The airway epithelium, which has a well-developed barrier regulated by tight junctions, is the first line of defense during respiratory virus infection. In upper airway human nasal epithelial cells (HNECs), however, the primary site of RSV infection, the mechanisms of replication and budding of RSV, and the epithelial cell responses, including the tight junctional barrier, remain unknown. To investigate the detailed mechanisms of replication and budding of RSV in HNECs and the epithelial cell responses, we established an RSV-infected model using human telomerase reverse transcriptase-transfected HNECs. We first found that the expression and barrier function of tight junction molecules claudin-4 and occludin were markedly induced together with production of proinflammatory cytokines interleukin 8 and tumor necrosis factor-alpha in HNECs after RSV infection, and the induction of tight junction molecules possibly contributed to budding of RSV. Furthermore, the replication and budding of RSV and the epithelial cell responses in HNECs were regulated via a protein kinase C delta/hypoxia-inducible factor-1 alpha/nuclear factor-kappa B pathway. The control of this pathway in HNECs may be useful not only for prevention of replication and budding of RSV, but also in therapy for RSV-induced respiratory pathogenesis.

DOI PubMed

Epithelial barrier and antigen uptake in lymphoepithelium of human adenoids

Noriko Ogasawara, Takashi Kojima, Mitsuru Go, Ken-Ichi Takano, Ryuta Kamekura, Tsuyoshi Ohkuni, Jun-Ichi Koizumi, Tomoyuki Masaki, Jun Fuchimoto, Kazufumi Obata, Makoto Kurose, Tomoko Shintani, Norimasa Sawada, Tetsuo Himi

ACTA OTO-LARYNGOLOGICA ( INFORMA HEALTHCARE ) 131 ( 2 ) 116 - 123 2011.02 [Refereed]

Invasion of antigens through the mucosal surface can be prevented by the common mucosal immune system, including Peyer's patches (PPs) and nasopharyngeal-associated lymphoreticular tissue (NALT). The adenoids (nasopharyngeal tonsils) comprise one of the NALTs and constitute the major part of Waldeyer's lymphoid ring in humans. However, the role of the lymphoepithelium, including M cells and dendritic cells (DCs), in the adenoids is unknown compared with the epithelium of PPs. NALTs also have unique functions such as the barrier of epithelial cells and uptake of antigens by M cells and DCs, and may play a crucial role in airway mucosal immune responses. The lymphoepithelium of adenoids has well-developed tight junctions that play an important role in the barrier function, the same as nasal epithelium but not palatine tonsillar epithelium. Tight junction molecules are expressed in both M cells and DCs as well as epithelial cells, and various antigens may be sampled, transported, and released to lymphocytes through the cells while they maintain the integrity of the epithelial barrier. This review summarizes the recent progress in our understanding of how M cells and DCs control the epithelial barrier in the adenoids.

DOI PubMed

Poly(I:C) reduces expression of JAM-A and induces secretion of IL-8 and TNF-alpha via distinct NF-kappa B pathways in human nasal epithelial cells

Tsuyoshi Ohkuni, Takashi Kojima, Noriko Ogasawara, Tomoyuki Masaki, Jun Fuchimoto, Ryuta Kamekura, Jun-ichi Koizumi, Shingo Ichimiya, Masaki Murata, Satoshi Tanaka, Tetsuo Himi, Norimasa Sawada

TOXICOLOGY AND APPLIED PHARMACOLOGY ( ACADEMIC PRESS INC ELSEVIER SCIENCE ) 250 ( 1 ) 29 - 38 2011.01 [Refereed]

Human nasal epithelium is an important physical barrier and innate immune defense protecting against inhaled substances and pathogens. Toll-like receptor (TLR) signaling, which plays a key role in the innate immune response, has not been well characterized in human nasal epithelial cells (HNECs), including the epithelial tight junctional barrier. In the present study, mRNAs of TLR1-10 were detected in hTERT-transfected HNECs, which can be used as an indispensable and stable model of normal HNECs, similar to primary cultured HNECs. To investigate the changes of tight junction proteins and the signal transduction pathways via TLRs in HNECs in vitro, hTERT-transfected HNECs were treated with TLR2 ligand P(3)CSK(4), TLR3 ligand poly(I:C), TLR4 ligand LPS, TLR7/8 ligand CL097, TLR8 ligand ssRNA40/LyoVec, and TLR9 ligand ODN2006. In hTERT-transfected HNECs, treatment with poly(I:C) significantly reduced expression of the tight junction protein JAM-A and induced secretion of proinflammatory cytokines IL-8 and TNF-alpha. Both the reduction of JAM-A expression and the induction of secretion of IL-8 and TNF-alpha after treatment with poly(I:C) were modulated by distinct signal transduction pathways via EGFR. PI3K, and p38 MAPK and finally regulated by a TLR3-mediated NF-kappa B pathway. The control of TLR3-mediated signaling pathways in HNECs may be important not only in infection by viral dsRNA but also in autoimmune diseases caused by endogenous dsRNA released from necrotic cells. (C) 2010 Elsevier Inc. All rights reserved.

DOI PubMed

Mucosal Immune Barrier and Antigen-Presenting System in Human Nasal Epithelial Cells

Tetsuo Himi, Ken-ichi Takano, Noriko Ogasawara, Mitsuru Go, Makoto Kurose, Jun-ichi Koizumi, Ryuta Kamekura, Atsushi Kondo, Tsuyoshi Ohkuni, Tomoyuki Masaki, Takashi Kojima, Norimasa Sawada, Hiroyuki Tsutsumi

RECENT ADVANCES IN TONSILS AND MUCOSAL BARRIERS OF THE UPPER AIRWAYS ( KARGER ) 72 28 - + 2011 [Refereed]

The upper respiratory tract including the nasal cavity, which is the first site of invading antigen exposure, plays a crucial role in host defense via the mucosal immune response. The epithelium of nasal mucosa forms a continuous barrier against a wide variety of exogenous antigens. The epithelial barrier function is regulated in large part by the apical-most intercellular junction, referred to as the tight junction. Antigen-presenting cells, particularly dendritic cells (DCs), are known to play an important role in human nasal mucosa. Recently, the author and colleagues discovered a new mechanism for pathogen uptake in the nasal mucosa, by which DCs open the tight junctions between epithelial cells and send dendrites outside the epithelium to directly sample the pathogen. In order to preserve the integrity of the epithelial barrier and penetrate beyond well-developed epithelial tight junctions, DCs express tight junction proteins. We also found that these DCs are activated by nasal epithelial-derived TSLP induced by stimuli such as cytokines and Toll-like receptor ligands. In this lecture, I will talk about the novel mechanisms in host defense in terms of innate immunity of the nasal mucosa from the point of view of the mucosal barrier function. Copyright (C) 2011 S. Karger AG, Basel

DOI PubMed

Carbon ion radiotherapy as an initial treatment in an unresectable head and neck soft tissue tumor

Noriko Ogasawara, Naoki Hyakushima, Keisuke Kikuchi, Tomonori Nagaya, Iwao Yoshioka, Masao Murakami, Yoshio Hishikawa

Practica Oto-Rhino-Laryngologica 104 ( 12 ) 899 - 903 2011 [Refereed]

Soft tissue tumor is a rare disease in the head and neck regions which is difficult to diagnose and treat. We report on a case of unresectable soft tissue tumor in the head and neck. The patient was a 41-year-old man who noticed some swelling on the right side of his neck which had started three months prior to presenting. A tumor was found in the right neck surrounding his common carotid artery which was judged unresectable because of its location and size. The differentiated diagnosis between a synovial sarcoma and a malignant peripheral nerve sheath tumor (MPNST) was difficult. The patient underwent carbon ion radiotherapy as an initial treatment in the Hyogo Ion Beam Medical Center. There was a partial response from the tumor in his neck tumor, but it metastasized to the lung and bone and the patient died of pulmonary failure nine months after the initial treatment.

DOI

c-Jun N-Terminal Kinase Is Largely Involved in the Regulation of Tricellular Tight Junctions via Tricellulin in Human Pancreatic Duct Epithelial Cells

Takashi Kojima, Jun Fuchimoto, Hiroshi Yamaguchi, Tatsuya Ito, Akira Takasawa, Takafumi Ninomiya, Shin Kikuchi, Noriko Ogasawara, Tsuyoshi Ohkuni, Tomoyuki Masaki, Koichi Hirata, Tetsuo Himi, Norimasa Sawada

JOURNAL OF CELLULAR PHYSIOLOGY ( WILEY-LISS ) 225 ( 3 ) 720 - 733 2010.12 [Refereed]

Tricellulin (TRIC) is a tight junction protein at tricellular contacts where three epithelial cells meet, and it is required for the maintenance of the epithelial barrier. To investigate whether TRIC is regulated via a c-Jun N-terminal kinase (JNK) pathway, human pancreatic HPAC cells, highly expressed at tricellular contacts, were exposed to various stimuli such as the JNK activators anisomycin and 12-O-tetradecanoylphorbol 13-acetate (TPA), and the proinflammatory cytokines IL-1 beta, TNF alpha, and IL-1 alpha. TRIC expression and the barrier function were moderated by treatment with the JNK activator anisomycin, and suppressed not only by inhibitors of JNK and PKC but also by siRNAs of TRIC. TRIC expression was induced by treatment with the PKC activator TPA and proinflammatory cytokines IL-1 beta, TNF alpha, and IL-1 alpha, whereas the changes were inhibited by a JNK inhibitor. Furthermore, in normal human pancreatic duct epithelial cells using hTERT-transfected primary cultured cells, the responses of TRIC expression to the various stimuli were similar to those in HPAC cells. TRIC expression in tricellular tight junctions is strongly regulated together with the barrier function via the JNK transduction pathway. These findings suggest that JNK may be involved in the regulation of tricellular tight junctions including TRIC expression and the barrier function during normal remodeling of epithelial cells, and prevent disruption of the epithelial barrier in inflammation and other disorders in pancreatic duct epithelial cells. J. Cell. Physiol. 225: 720-733, 2010. (C) 2010 Wiley-Liss, Inc.

DOI PubMed

ヒト鼻粘膜上皮細胞における新規タイト結合分子tricellulinの発現調節

大國毅, 小島隆, 小笠原徳子, 正木智之, 澤田典均, 氷見徹夫

日本鼻科学会会誌 ( (一社)日本鼻科学会 ) 49 ( 3 ) 425 - 425 2010.07

PPAR gamma agonists upregulate the barrier function of tight junctions via a PKC pathway in human nasal epithelial cells

Noriko Ogasawara, Takashi Kojima, Mitsuru Go, Tsuyoshi Ohkuni, Jun-ichi Koizumi, Ryuta Kamekura, Tomoyuki Masaki, Masaki Murata, Satoshi Tanaka, Jun Fuchimoto, Tetsuo Himi, Norimasa Sawada

PHARMACOLOGICAL RESEARCH ( ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD ) 61 ( 6 ) 489 - 498 2010.06 [Refereed]

Peroxisome proliferator activated (PPAR)gamma plays a critical role in the control of not only adipocyte differentiation, lipid metabolism and immunity but also the barrier functions of epithelial and endothelial cells. In the present study, to investigate effects of PPAR gamma agonists on the tight junctional barrier of human nasal epithelial cells (HNECs), hTERT-transfected HNECs, which highly express both PPAR gamma and tight junction proteins, were treated with the PPAR gamma agonists rosiglitazone and troglitazone. Treatment with the PPAR gamma agonists enhanced the barrier function of hTERT-transfected HNECs together with the upregulation of tight junction molecules claudin-1 and -4, occludin, and tricellulin at the transcriptional level. A significant increase of tight junction strands was also observed after treatment with rosiglitazone. Treatment with PPAR gamma agonists induced the activity of phospho-PKC in hTERT-transfected HNECs. The upregulation of the tight junction molecules in hTERT-transfected HNECs by rosiglitazone was inhibited by not only PPAR gamma antagonists GW9662 and T0070907, but also the panPKC inhibitor GF109203X. These findings suggest that PPAR gamma agonists upregulate the barrier function of tight junctions of human nasal epithelial cells via a PKC signaling pathway and could be novel drugs for protection against inhaled substances and pathogens in the airway epithelium of human nasal mucosa. (C) 2010 Elsevier Ltd. All rights reserved.

DOI PubMed

Toll様受容体刺激によるヒト鼻粘膜上皮細胞タイト結合分子発現変化について

大國毅, 小島隆, 小笠原徳子, 正木智之, 澤田典均, 氷見徹夫

日本耳鼻咽喉科学会会報 ( (一社)日本耳鼻咽喉科頭頸部外科学会 ) 113 ( 4 ) 405 - 405 2010.04

Thymic stromal lymphopoietin induces tight junction protein claudin-7 via NF-kappa B in dendritic cells

Ryuta Kamekura, Takashi Kojima, Akira Takashima, Jun-ichi Koizumi, Noriko Ogasawara, Mitsuru Go, Ken-ichi Takano, Masaki Murata, Satoshi Tanaka, Shingo Ichimiya, Tetsuo Himi, Norimasa Sawada

HISTOCHEMISTRY AND CELL BIOLOGY ( SPRINGER ) 133 ( 3 ) 339 - 348 2010.03 [Refereed]

Epithelial-derived thymic stromal lymphopoietin (TSLP) is an IL-7-like cytokine that triggers dendritic cell (DC)-mediated Th2-type inflammatory responses. The activated DCs can penetrate the epithelium to directly take up antigen without compromising the barrier function. Although it is reported that DCs express tight junction molecules and can establish tight junction-like structures with adjacent epithelial cells to preserve the epithelial barrier, the regulation of expression of tight junction molecules in DCs remains unknown. In the present study, to investigate the mechanical regulation of expression of tight junction molecules in DCs, XS52 DCs that was a long-term DC line established from the epidermis of a newborn BALB/c mouse, were treated with TSLP or toll-like receptor (TLR) ligands. In XS52 cells, tight junction molecules claudin-1, -3, -4, -6, -7, -8, and occludin were detected. mRNA expression of TSLP receptor and all these tight junction molecules was significantly increased in activated XS52 cells after treatment with TSLP. In addition, expression of claudin-7 protein was increased in dose- and time-dependent manner. In XS52 cells, which express TLR2, TLR3, TLR4, and TLR7, but not TLR9, expression of claudin-7 protein was also increased after treatment with ligands of TLR2, TLR4 or TLR7/8, Pam(3)Cys-Ser-(Lys)(4), LPS, or CL097. The NF-kappa B inhibitor IMD-0354 prevented upregulation of claudin-7 after treatment with TSLP or TLR ligands. These findings indicate that TSLP induces expression of tight junction protein claudin-7 in DCs via NF-kappa B as well as via TLRs and may control tight junctions of DCs to preserve the epithelial barrier during allergic inflammation.

DOI PubMed

RSウイルス感染ヒト鼻粘膜上皮細胞におけるタイト結合の誘導

正木智之, 小島隆, 大國毅, 小笠原徳子, 氷見徹夫, 村田雅樹, 田中敏, 澤田典均

日本病理学会会誌 ( (一社)日本病理学会 ) 99 ( 1 ) 191 - 191 2010.03

鼻粘膜上皮細胞における自然免疫toll like receptorによるタイト結合分子発現調節

大國毅, 小島隆, 小笠原徳子, 正木智之, 澤田均典, 氷見徹夫

アレルギーの臨床 ( (株)北隆館 ) 30 ( 1 ) 88 - 89 2010.01

The acid-sensing ion channel 2 (ASIC2) of ciliated cells in the developing rat nasal septum

Shin Kikuchi, Takafumi Ninomiya, Tomoyuki Kawamata, Noriko Ogasawara, Takashi Kojima, Nobutada Tachi, Haruyuki Tatsumi

ARCHIVES OF HISTOLOGY AND CYTOLOGY ( INT SOC HISTOLOGY & CYTOLOGY ) 73 ( 2 ) 81 - 89 2010 [Refereed]

The airway epithelium is exposed to an acidic environment in certain conditions. The acid-sensing ion channel 2 (ASIC2) belongs to the epithelial amiloride-sensitive sodium channel and degenerin (ENaC/DEG) family and is expressed on cilia of the respiratory epithelium. The aim of this study was to detect the expression of ASIC2 in the nasal septum in the embryonic stage of the rat. ASIC2 expression was not observed in the primary cilium but was found in some cilia on embryonic day 17 (E17). After E18, all cilia showed ASIC2 immunoreactivity. RT-PCR analysis revealed that ASIC2b, a subtype of ASIC2, was expressed in the nasal septum while ASIC2a was not. Quantitative Real-time RT-PCR studies indicated that the expression level of ASIC2 mRNA was highest on E21, just before birth. These results imply that ASIC2 plays little part in the development of the nasal septum epithelium. On the other hand, ASIC2, especially ASIC2b, may function for the survival and retention of ciliated cells of the nasal septum against dynamic changes in the pH environment at birth.

DOI PubMed

Expression and localization of tricellulin in human nasal epithelial cells in vivo and in vitro

Tsuyoshi Ohkuni, Takashi Kojima, Noriko Ogasawara, Tomoyuki Masaki, Takafumi Ninomiya, Shin Kikuchi, Mitsuru Go, Ken-ichi Takano, Tetsuo Himi, Norimasa Sawada

MEDICAL MOLECULAR MORPHOLOGY ( SPRINGER TOKYO ) 42 ( 4 ) 204 - 211 2009.12 [Refereed]

Tricellulin was identified as the first marker of the tricellular tight junction, which forms at the meeting points of three cells, and it is required for the maintenance of the transepithelial barrier. Although it is also considered to be important for the mucosal barrier of the upper respiratory tract, little is known about its expression and localization. In the present study, we examined the expression and localization of tricellulin in normal human nasal epithelial cells in vivo and in vitro, especially using primary cultures and telomerase reverse transcriptase (hTERT)-transfected cells. In human nasal epithelial cells in vivo and in vitro, mRNA and protein of tricellulin were detected. It was localized not only at tricellular contacts but also at bicellular borders, and in part colocalized with occludin. In human nasal epithelium, by immunoelectron microscopy analysis, tricellulin-associated gold particles were observed around the junction-like structure of the uppermost region. By treatment with 10% fetal bovine serum (FBS), expression of tricellulin mRNA was weakly increased, whereas that of bicellular tight junction molecules was strongly increased, in real-time PCR. These results suggest that tricellulin is stably expressed in human nasal epithelial cells and may play an important role for the sealing of the corner at tricellular contacts to prevent infiltration by various inhaled viruses and antigens.

DOI PubMed

Thymic stromal lymphopoietin enhances tight-junction barrier function of human nasal epithelial cells

Ryuta Kamekura, Takashi Kojima, Jun-ichi Koizumi, Noriko Ogasawara, Makoto Kurose, Mitsuru Go, Atsushi Harimaya, Masaki Murata, Satoshi Tanaka, Hideki Chiba, Tetsuo Himi, Norimasa Sawada

CELL AND TISSUE RESEARCH ( SPRINGER ) 338 ( 2 ) 283 - 293 2009.11 [Refereed]

Epithelial-derived thymic stromal lymphopoietin (TSLP) triggers dendritic cell (DC)-mediated Th2-type inflammatory responses and is a master switch for allergic inflammatory diseases. In the present study, the expression and induction of TSLP and the effects of TSLP on the tight-junctional barrier of human nasal epithelial cells (HNECs) have been investigated in order to elucidate the role of TSLP in allergic rhinitis. We have found high expression of TSLP in the epithelium from patients with allergic rhinitis with recruitment and infiltration of DCs. In vitro, TSLP is significantly produced in HNECs after treatment with a toll-like receptor 2 (TLR2) ligand, Pam(3)Cys-Ser-(Lys)(4), and a mixture of interleukin-1 beta and tumor necrosis factor-alpha. Treatment with TSLP rapidly enhances the barrier function of cultured HNECs, together with an increase of tight-junction proteins claudin-1, -4, -7, and occludin. The nasal-epithelial-derived TSLP thus not only activates DCs but also preserves the epithelial barrier via the upregulation of tight-junction proteins, thereby regulating antigen sensitization during the early stage of allergic rhinitis.

DOI PubMed

Induction of JAM-A during differentiation of human THP-1 dendritic cells

Noriko Ogasawara, Takashi Kojima, Mitsuru Go, Jun Fuchimoto, Ryuta Kamekura, Jun-ichi Koizumi, Tsuyoshi Ohkuni, Tomoyuki Masaki, Masaki Murata, Satoshi Tanaka, Shingo Ichimiya, Tetsuo Himi, Norimasa Sawada

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS ( ACADEMIC PRESS INC ELSEVIER SCIENCE ) 389 ( 3 ) 543 - 549 2009.11 [Refereed]

Junctional adhesion molecule (JAM)-A is not only localized at tight junctions of endothelial and epithelial cells but is also expressed on circulating leukocytes and dendritic cells (DCs). In the present study, to investigate the regulation of JAM-A in DCs, mature DCs were differentiated from the human monocytic cell THP-1 by treatment with IL-4, GM-CSF, TNF-alpha, and ionomycin, and some cells were pretreated with the PPAR-gamma agonists. In the THP-1 monocytes, mRNAs of tight junction molecules, occludin, tricellulin, JAM-A, ZO-1, ZO-2 and claudin-4, -7, -8, and -9 were detected by RT-PCR. In mature DCs that had elongated dendrites, mRNA and protein of JAM-A were significantly increased compared to the monocytes. PPAR-gamma agonists prevented the elongation of dentrites but not upregulation of JAM-A in mature DCs. These findings indicated that the induction of JAM-A Occurred during differentiation of human THP-1 DCs and was independent of PPAR-gamma and the p38 MAPK pathway. (C) 2009 Elsevier Inc. All rights reserved.

DOI PubMed

ヒト鼻粘膜上皮細胞を用いたRSウイルス感染モデルの確立と上皮タイト結合への影響

正木智之, 小島隆, 大國毅, 小笠原徳子, 岡林環樹, 藤井暢弘, 堤裕幸, 澤田典均, 氷見徹夫

日本鼻科学会会誌 ( (一社)日本鼻科学会 ) 48 ( 3 ) 323 - 323 2009.08

ヒト鼻粘膜の機能解析から見えてくること

氷見徹夫, 郷充, 近藤敦, 高野賢一, 正木智之, 小泉純一, 亀倉隆太, 大國毅, 小笠原徳子, 小島隆, 澤田典均

耳鼻咽喉科展望 ( 耳鼻咽喉科展望会 ) 52 ( 補冊1 ) 9 - 18 2009.08

ヒト鼻粘膜上皮の初代培養系を用いたバリア機能の解析は経鼻投与による炎症制御の方法論の確立に重要である。タイト結合はバリア機能に関連し物質の透過性に関与する因子のひとつであり、この機能を調節するメカニズムを解明することは炎症制御に重要である。さらに、樹状細胞やM細胞(micro-folds cell)のような抗原サンプリングに関与する免疫担当細胞の検討は経鼻投与によるアレルギー・感染などの免疫療法の効率化に寄与する。また、タイト結合などの細胞接着に関与する因子はウイルスの受容体であることが示されており、この意味ではウイルス感染の予防のための治療戦略としてタイト結合タンパクの研究を進めることは意義のあることと考えられる。ここでは鼻粘膜上皮と上皮内樹状細胞、さらに鼻粘膜のM細胞の存在について言及し、タイト結合とウイルス感染との関連、さらに、タイト結合タンパクの調節のメカニズムについても言及する。(著者抄録)

What was clarified from a function analysis of the human nasal mucosa?

Tetsuo Himi, Mitsuru Go, Atsushi Kondo, Ken-Ichi Takano, Tomoyuki Masaki, Jun-Ichi Koizumi, Ryuta Kamekura, Atsushi Ohkuni, Noriko Ogasawara, Takashi Kojima, Norimasa Sawada

Oto-Rhino-Laryngology Tokyo 52 ( 1 ) 9 - 18 2009.08

Analysis of the mucosal barrier function using a primary culture system of human nasal mucosal epithelium is important to establish a methodology of inflammation control by the transnasal drug delivery route. Tight junctions are one of the important factors contributing to the permeability of the nasal mucosa to drugs, and it is important to study the factors regulating the nasal mucosal permeability to drugs. Furthermore, examination of the immunocompetence of an individual by sampling cells such as dendritic cells and M cells may be expected to contribute to the establishment of immunotherapy for allergic rhinitis or upper respiratory infections using the transnasal approach. In addition, tight junctions are also known as one of the viral receptors, and it is important for the future to study the characteristics of tight junctions to develop treatment strategies for the prevention of viral infections.

ヒト鼻粘膜上皮細胞と樹状細胞のタイト結合蛋白はthymic stromal lymphopoietin(TSLP)によって誘導される

亀倉隆太, 小島隆, 小笠原徳子, 大國毅, 高野賢一, 郷充, 澤田典均, 氷見徹夫

日本耳鼻咽喉科学会会報 ( (一社)日本耳鼻咽喉科頭頸部外科学会 ) 112 ( 4 ) 376 - 376 2009.04

核内受容体PPAR-γを介したヒト鼻粘膜におけるタイト結合の発現調節機構

小笠原徳子, 小島隆, 郷充, 亀倉隆太, 大國毅, 正木智之, 村田雅樹, 田中敏, 千葉英樹, 氷見徹夫, 澤田典均

日本病理学会会誌 ( (一社)日本病理学会 ) 98 ( 1 ) 323 - 323 2009.03

Lingual hamartoma in a newborn with chromosome 2q terminal deletion

Nobuhiko Seki, Tomoko Shintani, Hiroshi Tsubota, Kazumasa Watanabe, Noriko Ogasawara, Yu-uki Ueda, Tetsuo Himi

International Journal of Pediatric Otorhinolaryngology Extra 3 ( 3 ) 109 - 112 2008.09 [Refereed]

Hamartoma, defined as tumour-like overgrowths of tissue, may occur in any organ in the body and is commonly seen in liver, spleen, kidney and lung, however, lingual hamartoma is a rare entity. Terminal deletion of chromosome 2q is a chromosomal abnormality causing various craniofacial malformations, and no reports can be obtained about patients who have chromosomal disorder presenting with lingual hamartoma. We describe the first case of lingual hamartoma in a patient with terminal deletion of chromosome 2, and summarize the clinical management and the histogenesis of lingual hamartoma from the literature. A 9-month-old girl who had chromosome 2q terminal deletion consulted Sapporo Medical University hospital for evaluation of upper airway obstruction. She had retractive breathing soon after birth and required treatment with continuous positive airway pressure (CPAP). Physical examination showed craniofacial abnormalities, such as round face, high palate, aural atresia, anotia and so on. Fiberoptic examination and CT scan revealed a mass on the right side of the tongue base. She underwent surgical resection and the tumour was pathologically diagnosed as hamartoma. After surgery, her respiratory condition improved to the extent where CPAP was withdrawn. There has been no tumour recurrence during the 1-year follow-up period. © 2007 Elsevier Ireland Ltd. All rights reserved.

DOI

Protein kinase C enhances tight junction barrier function of human nasal epithelial cells in primary culture by transcriptional regulation

Jun-ichi Koizumi, Takashi Kojima, Noriko Ogasawara, Ryuta Kamekura, Makoto Kurose, Mitsuru Go, Atsushi Harimaya, Masaki Murata, Makoto Osanai, Hideki Chiba, Tetsuo Himi, Norimasa Sawada

MOLECULAR PHARMACOLOGY ( AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS ) 74 ( 2 ) 432 - 442 2008.08 [Refereed]

The epithelium of upper respiratory tissues such as human nasal mucosa forms a continuous barrier via tight junctions, which is thought to be regulated in part through a protein kinase C (PKC) signaling pathway. To investigate the mechanisms of the regulation of PKC-mediated tight junction barrier function of human nasal epithelium in detail, primary human nasal epithelial cells were treated with the PKC activator 12-O-tetradecanoylophorbol-13-acetate (TPA). In primary human nasal epithelial cells, treatment with TPA led not only to activation of phosphorylation of PKC, myristoylated alanine-rich C kinase substrate, and mitogen-activated protein kinase but also expression of novel PKC-delta, PKC-theta, and PKC-epsilon. Treatment with TPA increased transepithelial electrical resistance, with tight junction barrier function more than 4-fold that of the control, together with up-regulation of tight junction proteins, occludin, zona occludens (ZO)-1, ZO-2 and claudin-1 at the transcriptional level. Furthermore, it affected the subcellular localization of the tight junction proteins and the numbers of tight junction strands. The up-regulation of barrier function and tight junction proteins was prevented by a pan-PKC inhibitor, and the inhibitors of PKC-delta and PKC-theta but not PKC-epsilon. In primary human nasal epithelial cells, transcriptional factors GATA-3 and -6 were detected by reverse transcription-polymerase chain reaction. The knockdown of GATA-3 using RNA interference resulted in inhibition of up-regulation of ZO-1 and ZO-2 by treatment with TPA. These results suggest that TPA-induced PKC signaling enhances the barrier function of human nasal epithelial cells via transcriptional up-regulation of tight junction proteins, and the mechanisms may contribute to a drug delivery system.

DOI PubMed

ヒト鼻粘膜上皮バリアにおけるPKCシグナルを介したタイト結合の調節機構

小島隆, 小泉純一, 小笠原徳子, 亀倉隆太, 黒瀬誠, 今野信宏, 郷充, 高野賢一, 氷見徹夫, 澤田典均

Inflammation and Regeneration ( (一社)日本炎症・再生医学会 ) 28 ( 4 ) 354 - 354 2008.07

Expression of tight junction proteins in epithelium including Ck20-positive M-like cells of human adenoids in vivo and in vitro

Ken-ichi Takano, Takashi Kojima, Noriko Ogasawara, Mitsuru Go, Shin Kikuchi, Takafumi Ninomiya, Makoto Kurose, Jun-ichi Koizumi, Ryuta Kamekura, Masaki Murata, Satoshi Tanaka, Hideki Chiba, Tetsuo Himi, Norimasa Sawada

JOURNAL OF MOLECULAR HISTOLOGY ( SPRINGER ) 39 ( 3 ) 265 - 273 2008.06 [Refereed]

The human adenoid epithelium forms a continuous barrier against a wide variety of exogenous antigens. In this study, to elucidate the structures of the epithelial barrier in the human adenoid, including M-cells, we identified M-cells using an anti-cytokeratin 20 (Ck20) antibody and investigated expression of tight junction proteins in human adenoid epithelium in vivo and in vitro. In human adenoid epithelium and primary cultures, mRNAs of occludin, junctional adhesion molecule-A, ZO-1, and claudin-1, -4, -7, and -8 were detected by reverse transcription-polymerase chain reaction, whereas claudin-2 and -9 were expressed in vitro. In the epithelium in vivo, some Ck20-positive cells were randomly observed and indicated pocket-like structures, whereas Ck7 was positive in almost cells. Transmission electron microscopy revealed that Ck20-associated gold particles could be identified in M-like cells which had short microvilli and harboured the lymphocyte in the pocket-like structure. In primary cultures in vitro, Ck20-positive cells were also detected and had a function to take up fluorescent microparticles. In Ck20-positive cells in vivo and in vitro, expression of occludin, ZO-1, claudin-1 and -7 were observed at cell borders. These results indicate that the epithelial barrier of the human adenoid is stably maintained by expression of tight junction proteins in the epithelium including Ck20-positive M-like cells.

DOI PubMed

Expression of thymic stromal lymphopoietin (TSLP) in allergic rhinitis : Induction of tight junction proteins in human nasal epithelial cells and dendritic cells by epithelial-derived TSLP

KAMEKURA Ryuta, KOJIMA Takashi, KOIZUMI Jun-ichi, OGASAWARA Noriko, KUROSE Makoto, TAKANO Ken-ichi, GO Mitsuru, HIMI Tetsuo, SAWADA Norimasa

Inflammation and Regeneration ( The Japanese Society of Inflammation and Regeneration ) 28 ( 3 ) 160 - 165 2008.05

Thymic stromal lymphopoietin (TSLP) is an interleukin 7-like cytokine that triggers dendritic cell (DC)-mediated T helper 2-type inflammatory responses and is considered to be a master switch for allergic inflammation such as that in asthma and atopic dermatitis. Furthermore, proinflammatory cytokines and Toll-like receptor ligands can induce TSLP production in human bronchial epithelial cells and human keratinocytes. We first found high expression of endogenous TSLP in the epithelium of allergic rhinitis with recruitment and infiltration of DCs. In culture, the TSLP production in human nasal epithelial cells was markedly and significantly increased by treatment with the proinflammatory cytokines interleukin 1β/tumor necrosis factor-α and a Toll-like receptor 2 ligand, P₃CSK₄. Since it is also thought that TSLP expression not only activates DCs but also affects the epithelial barrier in allergic rhinitis, we investigated the effects of TSLP on tight junctions of human nasal epithelial cells and DCs in vitro. Treatment with TSLP enhanced the barrier function of human nasal epithelial cells in vitro together with an increase of the tight junction proteins claudin-1,-4,-7, and occludin. Furthermore, TSLP could exclusively induce claudin-7 expression in mouse DC line XS52, which expressed tight junction molecules claudin-1,-3,-4,-6,-7,-8, occludin and tricellulin.
These findings suggest that nasal epithelial-derived TSLP plays an important role in allergic rhinitis as well as asthma and atopic dermatitis and may control tight junctions of epithelial cells and DCs to preserve the epithelial barrier and promote direct sampling of antigens by DCs.

DOI CiNii

当科における副咽頭間隙悪性腫瘍症例の検討、及びアプローチ法としてのmaxillary swingの経験

坪田大, 郷充, 金泉悦子, 関伸彦, 小笠原徳子, 新谷朋子, 氷見徹夫

頭頸部癌 ( (一社)日本頭頸部癌学会 ) 34 ( 2 ) 212 - 212 2008.05

ヒト鼻粘膜上皮バリアにおけるPKCシグナルを介したタイト結合の調節機構

小泉純一, 小島隆, 黒瀬誠, 亀倉隆太, 小笠原徳子, 今野信宏, 郷充, 澤田典均, 氷見徹夫

日本鼻科学会会誌 ( (一社)日本鼻科学会 ) 46 ( 3 ) 263 - 263 2007.08

中耳結核の3症例

小笠原徳子, 新谷朋子, 関伸彦, 金泉悦子, 坪田大, 氷見徹夫

耳鼻咽喉科臨床補冊 ( 耳鼻咽喉科臨床学会 ) ( 補冊120 ) 55 - 55 2007.07

テロメラーゼ遺伝子導入培養ヒト鼻粘膜上皮細胞のタイト結合の発現と機能

小島隆, 黒瀬誠, 亀倉隆太, 小泉純一, 小笠原徳子, 氷見徹夫, 澤田典均

Inflammation and Regeneration ( (一社)日本炎症・再生医学会 ) 27 ( 4 ) 439 - 439 2007.07

Angioleiomyoma of the left subcutaneous external nose

Noriko Ogasawara, Hiroshi Tsubota, Tomoko Shintani, Masako Watanabe, Kazumasa Watanabe, Nobuhiko Seki, Tetsuo Himi

Practica Oto-Rhino-Laryngologica ( Society of Practical Otolaryngology ) 100 ( 9 ) 709 - 713 2007 [Refereed]

Angioleiomyoma is a benign tumor composed of smooth muscle cells and vascular endothelial cells, which is most commonly found in the uterus, skin, and alimentary canal as a painful mass. In the head and neck region, the incidence of this tumor is rare and pain is usually absent. We report a rare case of angioleiomyoma occurring in the left subcutaneous extrernal nose. A 41-year-old man visited our hospital complaining of a swelling on the left side of the nose. Physical examination revealed a soft mass in the left subcutaneous extrernal nose. CT scan and MRI with gadolinium enhancement showed well-enhanced mass in the left subcutaneous extrernal nose without bone destruction or apparent invasion into the left nasal cavity. Aspiration biopsy cytology revealed blood only. The tumor was fully excised without major intraoperative bleeding, and the postoperative course was successful. Immunohistochemical study revealed postive staining for vimentin and α-smooth muscle actin in tumor cells, and the tumor was diagnosed as angioleiomyoma. For over a year following surgery, there has been no evidence of recurrence.

DOI

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