Faculty Profiles - Seiichiro Makihara

Papers - Seiichiro Makihara

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Pulmonary function in patients with chronic rhinosinusitis and allergic rhinitis Reviewed

S. Kariya, M. Okano, T. Oto, T. Higaki, S. Makihara, T. Haruna, K. Nishizaki

Journal of Laryngology and Otology 128 ( 3 ) 255 - 262 2014.3

Publishing type：Research paper (scientific journal)

Background: A close relationship between upper and lower respiratory tract diseases has been reported. However, little is known about pulmonary function in patients with upper respiratory tract diseases. Methods: Pulmonary function was measured in: 68 patients with chronic rhinosinusitis without nasal polyps, 135 patients with chronic rhinosinusitis with nasal polyps, 89 patients with allergic rhinitis and 100 normal control subjects. The relationships between pulmonary function and clinical parameters were assessed. These parameters included radiographic severity of chronic rhinosinusitis, serum total immunoglobulin E levels, concentrations of cytokines in nasal secretions and exhaled nitric oxide levels. Results: The pulmonary function of patients with chronic rhinosinusitis was significantly affected. The level of interleukin-5 in nasal secretions was significantly correlated with pulmonary function in patients with chronic rhinosinusitis. Conclusion: The findings indicated latent obstructive lung function changes in chronic rhinosinusitis patients. The cytokines in nasal secretions might be related to obstructive lung function changes in chronic rhinosinusitis.

DOI： 10.1017/S0022215114000450

【スギ花粉症の発症と初期治療】鼻噴霧ステロイド薬を用いた初期治療の有効性

小山貴久, 岡野光博, 春名威範, 野山和廉, 假谷伸, 檜垣貴哉, 牧原靖一郎, 西崎和則

臨床免疫・アレルギー科 60 ( 6 ) 664 - 667 2013.12

当院における外来化学療法室の現状と課題

滝本秀隆, 坂本路代, 藤浦美佐, 土佐直子, 亀井美紀, 能願美由紀, 中尾三千代, 乃一真由美, 香川秀子, 永田拓也, 井上秀幸, 木村圭吾, 村岡篤, 平下浩司, 牧原靖一郎, 水野全裕, 川田昭徳, 香川労災病院化学療法委員会

香川労災病院雑誌 ( 19 ) 1 - 5 2013.10

鼻出血を契機に発見された鼻腔原発のglomangiopericytomaの1例 Reviewed

大道亮太郎, 假谷伸, 岡野光博, 牧原靖一郎, 小野田友男, 江口元治, 西崎和則

頭頸部外科 23 ( 2 ) 141 - 144 2013.10

Language：Japanese Publisher：(NPO)日本頭頸部外科学会

glomangiopericytomaは鼻副鼻腔原発の血管周囲筋様細胞の表現型を伴う境界から低悪性度の新生物である。その発生頻度は全鼻副鼻腔腫瘍のうち1%以下とされており、非常にまれな腫瘍である。この腫瘍は従来hemangiopericytomaの一亜型とされてきたが、一般的な軟部組織に発生するhemangiopericytomaとは発生部位、生物学的挙動、組織学的特徴の観点から区別され、2005年のWHO基準にて正式に疾患分類として登録された。比較的新しい疾患概念であることなどから、hemangiopericytomaとの鑑別が十分なされていないことがあり、注意を要する疾患とされている。われわれは今回鼻出血を主訴に来院した右鼻腔原発のglomangiopericytomaに対し、内視鏡下に切除手術を施行し、良好な経過を得た1例を経験したので報告する。(著者抄録)

Other Link： https://search.jamas.or.jp/default/link?pub_year=2013&ichushi_jid=J04210&link_issn=&doc_id=20131127350004&doc_link_id=10.5106%2Fjjshns.23.141&url=https%3A%2F%2Fdoi.org%2F10.5106%2Fjjshns.23.141&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Neutralizing antibody against granulocyte/macrophage colony-stimulating factor inhibits inflammatory response in experimental otitis media. Reviewed International journal

Shin Kariya, Mitsuhiro Okano, Takaya Higaki, Seiichiro Makihara, Takenori Haruna, Motoharu Eguchi, Kazunori Nishizaki

The Laryngoscope 123 ( 6 ) 1514 - 8 2013.6

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

OBJECTIVES/HYPOTHESIS: Granulocyte/macrophage colony-stimulating factor is important in the pathogenesis of acute and chronic inflammatory disease. We hypothesized that granulocyte/macrophage colony-stimulating factor plays a pivotal role in middle ear inflammation and that neutralization of granulocyte/macrophage colony-stimulating factor would inhibit neutrophil migration into the middle ear and production of inflammatory mediators. STUDY DESIGN: Animal experiment. METHODS: We used transtympanic administration of lipopolysaccharide, a major component of gram-negative bacteria, into mice to induce an experimental otitis media. Control mice received injection of phosphate-buffered saline into the middle ear cavity. Mice were systemically treated with granulocyte/macrophage colony-stimulating factor neutralizing antibody or control immunoglobulin G via intraperitoneal injection 2 hours before transtympanic injection of lipopolysaccharide or phosphate-buffered saline. Middle ear effusions were collected. Concentrations of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, keratinocyte chemoattractant, and macrophage inflammatory protein-2 in middle ear effusions were measured by enzyme-linked immunosorbent assay. Histologic examination of the middle ear was also performed. RESULTS: Transtympanic injection of lipopolysaccharide upregulated levels of granulocyte/macrophage colony-stimulating factor, IL-1β, TNF-α, keratinocyte chemoattractant, and macrophage inflammatory protein-2 in the middle ear. Concentrations of cytokines and chemokines were significantly decreased in mice injected with granulocyte/macrophage colony-stimulating factor neutralizing antibody. Infiltration of inflammatory cells into the middle ear cavity induced by lipopolysaccharide was also significantly reduced by neutralization of granulocyte/macrophage colony-stimulating factor. CONCLUSIONS: Systemic injection of granulocyte/macrophage colony-stimulating factor neutralizing antibody inhibits the middle ear inflammation induced by lipopolysaccharide in mice. Our findings suggest that granulocyte/macrophage colony-stimulating factor may offer a novel therapeutic target for the management of intractable otitis media.

DOI： 10.1002/lary.23795

鼻中隔膿瘍を伴った浸潤型蝶形骨洞アスペルギルス症例 Reviewed

牧原靖一郎, 竹内彩子, 山本美紀, 妹尾一範, 赤木成子, 福本晶, 津村宗近, 石原久司, 假谷伸, 岡野光博, 西崎和則

耳鼻咽喉科臨床 106 ( 3 ) 213 - 220 2013.3

Authorship：Lead author Language：Japanese Publisher：耳鼻咽喉科臨床学会

86歳男。鼻中隔膿瘍は切開排膿によって改善した。蝶形骨洞アスペルギルス症に対しては内視鏡下鼻内副鼻腔手術による真菌塊除去後にボリコナゾール(VRCZ)投与を開始したが、症状は増悪した。その後、鼻中隔膿瘍の菌培養検査での真菌MIC値を参考にして抗真菌剤をミカファンギンナトリウムとイトラコナゾールに変更したところ、症状は改善した。本例はVRCZに抵抗性のアスペルギルス症であり、真菌MIC値は薬剤選択に非常に有用であった。

Other Link： https://search.jamas.or.jp/default/link?pub_year=2013&ichushi_jid=J00580&link_issn=&doc_id=20130227280005&doc_link_id=10.5631%2Fjibirin.106.213&url=https%3A%2F%2Fdoi.org%2F10.5631%2Fjibirin.106.213&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

Characterization of IL-18 expression and release in the pathogenesis of chronic rhinosinusitis. Reviewed International journal

Mitsuhiro Okano, Tazuko Fujiwara, Seiichiro Makihara, Rumi Fujiwara, Takaya Higaki, Shin Kariya, Yohei Noda, Takenori Haruna, Kazunori Nishizaki

International archives of allergy and immunology 160 ( 3 ) 275 - 86 2013

Language：English Publishing type：Research paper (scientific journal) Publisher：KARGER

BACKGROUND: Interleukin-18 (IL-18) is a member of the IL-1 cytokine family that affects chronic inflammation. We sought to characterize IL-18 expression and investigate its release during chronic rhinosinusitis (CRS). METHODS: The expression of IL-18 in nasal polyps (NPs) and uncinate tissues (UTs) from both CRS and non-CRS patients was examined via immunohistochemistry. After culturing dispersed NP cells (DNPCs) with or without various stimulations, IL-18 levels were measured in the culture supernatants. Furthermore, the effect of IL-18 neutralization on staphylococcus enterotoxin B (SEB)-induced cytokine production was also examined. RESULTS: Similar expression of IL-18 in the epithelial layers was observed between the NPs and UTs. However, there was a significantly higher number of IL-18(+) cells in the lamina propria from NPs compared to UTs without CRS. This increased number was significantly correlated with the radiological severity of sinusitis and local eosinophilia. After the dispersion, IL-18 was spontaneously released by NP cells in a phase-dependent manner. While SEB, fungal antigens, and TLR agonists did not enhance the release, exposure to protease or one cycle of a freeze-and-thaw treatment did induce release of IL-18 from rested DNPCs. In addition, neutralization of IL-18 significantly suppressed SEB-induced IL-5, IL-13, and IFN-γ, but not IL-17A production. CONCLUSIONS: These results suggest that the pro-inflammatory effect of IL-18 released by danger signals may be involved in the pathogenesis of CRS, which includes eosinophilic inflammation and NP formation, via the augmentation of both Th2- and Th1-associated cytokine production.

DOI： 10.1159/000341668

Early interventional treatment with intranasal corticosteroids compared with postonset treatment in pollinosis. Reviewed International journal

Takaya Higaki, Mitsuhiro Okano, Seiichiro Makihara, Tazuko Fujiwara, Takenori Haruna, Yohei Noda, Shin Kariya, Kazunori Nishizaki

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology 109 ( 6 ) 458 - 64 2012.12

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE INC

BACKGROUND: The usefulness of early interventional treatment (EIT) with intranasal corticosteroids (INSs) compared with postonset treatment (POT) has not been clarified. OBJECTIVES: To study the efficacy and safety of EIT with INSs compared with POT and placebo in Japanese cedar/cypress pollinosis. METHODS: We designed a 3-armed, double-blinded, randomized, placebo-controlled trial. Patients received mometasone furoate nasal spray (EIT group: n = 25), placebo (n = 25), or 4 weeks of placebo followed by 8 weeks of mometasone (POT group: n = 25) for a 12-week period starting on February 1, 2011. The primary end point was the comparison of the total nasal symptom score (TNSS) among the 3 groups. Total ocular symptom score (TOSS), total naso-ocular symptom score (TSS), Allergic Rhinitis and Its Impact (ARIA) on Asthma classification, and safety were the main secondary end points. RESULTS: The placebo and POT groups, but not the EIT group, had a significant exacerbation of TNSS and TOSS soon after the start of pollen counts being high on consecutive days. The 12-week mean TSS in the EIT group (score, 2.3) was significantly lower than in the placebo (5.0; P < .01) and POT (3.9; P = .03) groups. All patients in the placebo and POT groups were classified as having persistent rhinitis, whereas 80% of the EIT group met the ARIA classification criteria (P = .03). The quality-of-life score and nasal eosinophil cationic protein levels were lower in the EIT and POT groups compared with the placebo group. Daytime sleepiness, smell disturbance, and the mean dose of loratadine taken as the rescue medication were similar. Treatment with mometasone was well tolerated. CONCLUSION: EIT with INSs is superior to POT in controlling pollinosis.

DOI： 10.1016/j.anai.2012.08.016

Roles of IL-17, Th1, and Tc1 cells in patients with IgG4-related sclerosing sialadenitis. Reviewed International journal

Nobuo Ohta, Seiichiro Makihara, Mitsuhiro Okano, Kazuya Kurakami, Akihiro Ishida, Takatoshi Furukawa, Yusuke Suzuki, Tomoo Watanabe, Seiji Kakehata, Masaru Aoyagi

The Laryngoscope 122 ( 10 ) 2169 - 74 2012.10

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

OBJECTIVES/HYPOTHESIS: Immunoglobulin G4 (IgG4)-related sclerosing sialadenitis is a recently recognized disease entity characterized by high serum IgG4 concentration and IgG4-producing plasma cell expansion in affected organs, which show fibrotic or sclerotic changes. However, little is known about the roles of CD4+ and CD8+ T cells or interleukin (IL)-17 in this disease. The purpose of this study was to evaluate the characteristics of CD4+ and CD8+ T cells and IL-17 in patients with IgG4-related sclerosing sialadenitis. STUDY DESIGN: A retrospective clinical study at the Yamagata University School of Medicine. METHODS: The patient group consisted of six males and four females with an average age of 57.9 years (range, 38 to 73 years). Subsets of T helper (Th)1, Th2, T cytotoxic type (Tc)1, and Tc2 cells from patients with IgG4-related sclerosing sialadenitis were examined by using intracellular cytokine flow cytometry. Expression of IL-17 in the patients' lesions was also investigated immunohistochemically. RESULTS: Six patients with IgG4-related sclerosing sialadenitis with high ratios of IgG4/IgG and prominent infiltration of IgG4-positive plasmacytes in the involved salivary glands had systemic complications, including pancreatitis, retroperitoneal fibrosis, and/or inflammatory pseudotumor of the lung after the initial swelling of the salivary glands. Populations of Th1 and Tc1 cells were significantly greater in IgG4-related sclerosing sialadenitis than in the controls (P < .05), but Th2 and Tc2 cell populations were not significantly increased. Expression of IL-17 was observed in the lesions of affected patients. CONCLUSIONS: Increases in Th1 and Tc1 cell populations and IL-17 expression might be involved in the mechanism of pathogenesis of IgG4-related sclerosing sialadenitis.

DOI： 10.1002/lary.23429

COX/PGE<inf>2</inf> axis critically regulates effects of LPS on eosinophilia-associated cytokine production in nasal polyps Reviewed

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

Clinical and Experimental Allergy 42 ( 8 ) 1217 - 1226 2012.8

Publishing type：Research paper (scientific journal)

Background: Lipopolysaccharide (LPS) has shown heterogeneous effects on eosinophilic inflammation in airways. However, little is known about how LPS regulates pathogenesis of chronic rhinosinusitis with nasal polyps, a major form of eosinophilic inflammation in the upper airway. Objective: We sought to investigate the effect of LPS on cytokine production by dispersed nasal polyp cells (DNPCs). Methods: Either diclofenac-treated or untreated DNPCs were cultured with or without staphylococcal enterotoxin B (SEB) in the presence or absence of LPS, after which the levels of IL-5, IL-13, IL-17A and IFN-γ within the supernatant were measured. The effects of PGE2 on LPS-induced responses by diclofenac-treated DNPCs were also examined. LPS-induced PGE2 production and mRNA expression of COX-1, COX-2 and microsomal PGE2 synthase-1 (m-PGES-1) were measured. Results: Staphylococcal enterotoxin B induced IL-5, IL-13, IL-17A and IFN-γ production by DNPCs. Pre-treatment with LPS prior to SEB stimulation inhibited production of these cytokines. After stimulation with LPS, PGE2 production and expression of COX-2 and m-PGES-1 mRNA by DNPCs increased significantly. In the presence of diclofenac, the suppressive effects of LPS were eliminated. LPS pre-treatment enhanced SEB-induced IL-5, IL-13 and IL-17A production in diclofenac-treated DNPCs, while addition of PGE2 inhibited IL-5, IL-13 and IFN-γ production. LPS alone induced IL-5, IL-13 and IFN- γ production by diclofenac-treated DNPCs, while the addition of EP2 and EP4 receptor-selective agonists, as well as PGE2 itself, inhibited IL-5 and IL-13 production. Conclusions and Clinical Relevance: These results suggest that the regulatory effects of LPS on eosinophilic airway inflammation are controlled via the COX-2/PGE2 axis. For clinical implications, indiscreet use of non-steroidal anti-inflammatory drugs should be avoided in patients with chronic rhinosinusitis with nasal polyps. © 2012 Blackwell Publishing Ltd.

DOI： 10.1111/j.1365-2222.2012.04015.x

滲出性中耳炎を合併した翼口蓋窩嚢胞例 Reviewed

牧原靖一郎, 岡野光博, 折田頼尚, 小野田友男, 假谷伸, 津村宗近, 西崎和則

耳鼻咽喉科臨床 105 ( 7 ) 631 - 636 2012.7

Authorship：Lead author Language：Japanese Publisher：耳鼻咽喉科臨床学会

67歳女性。咬合時の左顔面違和感を主訴に近医を受診、CT検査にて左翼口蓋窩腫瘍を疑われ、著者らの施設へ紹介となった。所見では副鼻腔CTで左上顎洞後方、翼口蓋窩に長径14mmと短径6mmのニ房性の嚢胞状腫瘤が認められた。また、MRIでは同部位にT1にて低信号、T2にて低信号と高信号が混在する腫瘤が確認された。以上、これらの画像所見を踏まえ、本症例は嚢胞性病変を考え、しばらく経過観察としていたが、左滲出性中耳炎を合併し、MRIで腫瘤サイズの増大とともに左乳突蜂巣に液体貯留が認められた。そこで、診断確定目的で内視鏡下鼻内副鼻腔手術を行なったところ、病理組織学的に翼口蓋窩に発生した類表皮嚢胞と診断された。経過は術後より咬合時の左顔面違和感が改善し、左滲出性中耳炎も治癒が得られた。目下、術後1年経過で開放部の閉塞や滲出性中耳炎の再燃はみられていない。

Other Link： https://search.jamas.or.jp/default/link?pub_year=2012&ichushi_jid=J00580&link_issn=&doc_id=20120705310005&doc_link_id=10.5631%2Fjibirin.105.631&url=https%3A%2F%2Fdoi.org%2F10.5631%2Fjibirin.105.631&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

Early interventional treatment with intranasal mometasone furoate in Japanese cedar/cypress pollinosis: a randomized placebo-controlled trial. Reviewed International journal

Seiichiro Makihara, Mitsuhiro Okano, Tazuko Fujiwara, Masayo Kimura, Takaya Higaki, Takenori Haruna, Yohei Noda, Kengo Kanai, Shin Kariya, Kazunori Nishizaki

Allergology international : official journal of the Japanese Society of Allergology 61 ( 2 ) 295 - 304 2012.6

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：JAPANESE SOCIETY ALLERGOLOGY

BACKGROUND: Little is known about the safety and effectiveness of early interventional treatment (EIT) with intranasal corticosteroids for seasonal allergic rhinitis. We designed a double-blinded, randomized, placebo-controlled 12-week trial of EIT with mometasone furoate nasal spray (MFNS) for Japanese cedar/cypress pollinosis (JCCP). METHODS: A total of 50 JCCP patients received MFNS (200μg once daily: n = 25) or placebo (n = 25) starting on February 1, 2010. Treatments continued until the end of April. The primary endpoint was the comparison of the total nasal symptom score (TNSS) between the MFNS and placebo groups. The secondary endpoints included comparisons of QOL, daytime sleepiness, nasal ECP levels, and safety. RESULTS: Continuous dispersion of Japanese cedar pollen began on February 22. Although the placebo group showed a significant worsening of symptoms after the start of the continuous dispersion, no worsening occurred in the MFNS group. A significant difference in the TNSS between the two groups was seen starting at 4 weeks after the treatment. Similar results were seen for QOL and sleepiness. Nasal ECP levels in March were significantly lower in the MFNS group. A total of 56% of the MFNS group progressed to a persistent allergic rhinitis state in accordance with the ARIA classification, as opposed to 84% of the placebo group. MFNS was well tolerated, and the plasma cortisol concentrations were similar between the two groups. CONCLUSIONS: EIT with MFNS for JCCP is both safe and effective. This treatment can potentially lessen symptoms and help pollinosis patients remain in the intermittent state.

DOI： 10.2332/allergolint.11-OA-0382

Lipopolysaccharide induces proinflammatory cytokines and chemokines in experimental otitis media through the prostaglandin D<inf>2</inf> receptor (DP)-dependent pathway Reviewed

M. Eguchi, S. Kariya, M. Okano, T. Higaki, S. Makihara, T. Fujiwara, K. Nagata, H. Hirai, S. Narumiya, M. Nakamura, K. Nishizaki

Clinical and Experimental Immunology 163 ( 2 ) 260 - 269 2011.2

Publishing type：Research paper (scientific journal)

Otitis media is one of the most common and intractable ear diseases, and is the major cause of hearing loss, especially in children. Multiple factors affect the onset or development of otitis media. Prostaglandin D2 is the major prostanoid involved in infection and allergy. However, the role of prostaglandin D2 and prostaglandin D2 receptors on the pathogenesis of otitis media remains to be determined. Recent studies show that D prostanoid receptor (DP) and chemoattractant receptor-homologous molecule expressed on T helper type 2 (Th2) cells (CRTH2) are major prostaglandin D2 receptors. In this study, homozygous DP single gene-deficient (DP-/-) mice, CRTH2 single gene-deficient (CRTH2-/-) mice and DP/CRTH2 double gene-deficient (DP-/- CRTH2-/-) mice were used to investigate the role of prostaglandin D2 and its receptors in otitis media. We demonstrate that prostaglandin D2 is induced by lipopolysaccharide (LPS), a major component of Gram-negative bacteria, and that transtympanic injection of prostaglandin D2 up-regulates macrophage inflammatory protein 2 (MIP-2), interleukin (IL)-1β and IL-6 in the middle ear. We also show that middle ear inflammatory reactions, including infiltration of inflammatory cells and expression of MIP-2, IL-1β and IL-6 induced by LPS, are reduced significantly in DP-/- mice and DP-/- CRTH2-/- mice. CRTH2-/- mice display inflammatory reactions similar to wild-type mice. These findings indicate that prostaglandin D2 may play significant roles in LPS-induced experimental otitis media via DP. © 2010 The Authors. Clinical and Experimental Immunology © 2010 British Society for Immunology.

DOI： 10.1111/j.1365-2249.2010.04292.x

Role of fungal antigens in eosinophilia-associated cellular responses in nasal polyps: A comparison with enterotoxin Reviewed

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

Clinical and Experimental Allergy 41 ( 2 ) 171 - 178 2011.2

Publishing type：Research paper (scientific journal)

Summary: Background Fungi and/or Staphylococcus aureus enterotoxins (SEs) may participate in the pathogenesis of eosinophilic inflammation in cases of chronic rhinosinusitis with nasal polyps (CRSwNP).Objective We sought to determine the effects of fungal antigens on eosinophilia-associated cellular responses in nasal polyps.Methods Dispersed nasal polyp cells (DNPCs) were prepared from 13 patients with CRSwNP. DNPCs were cultured with fungal extracts (Aspergillus, Alternaria and Candida) or SEB for 72 h, after which the levels of IL-5, IL-13 and RANTES were measured within the supernatant. Responses to β-d-glucan, mannan and chitin were also examined.Results 38.5%, 69.2% and 30.8% of DNPCs produced IL-5, IL-13 and RANTES, respectively, in response to 200 μg/mL of Aspergillus. 53.8%, 53.8% and 7.7% of DNPCs produced IL-5, IL-13 and RANTES, respectively, in response to 200 μg/mL of Alternaria. 53.8%, 38.5% and 15.4% of DNPCs produced IL-5, IL-13 and RANTES, respectively, in response to 200 μg/mL of Candida. All DNPCs produced these cytokines in response to 0.1 μg/mL of SEB. SEB induced significantly greater cytokine levels than the fungal extracts. No correlation between cytokine production following exposure to each of the fungal extracts or SEB and various clinical features, including nasal polyp eosinophilia and radiological severity of sinusitis was observed. Neither sensitization to fungus nor comorbidity with bronchial asthma was correlated with the fungal extract-induced cytokine production by DNPCs. β-d-glucan, mannan and chitin did not induce significant cytokine production.Conclusions These results suggest that, although DNPCs produce IL-5, IL-13 and RANTES in response to fungal extracts, fungal antigens including major carbohydrates are less capable of inducing eosinophilia-associated cellular responses in nasal polyps than SEB. © 2011 Blackwell Publishing Ltd.

DOI： 10.1111/j.1365-2222.2010.03584.x

Characterization of pollen antigen-induced IL-31 production by PBMCs in patients with allergic rhinitis. Reviewed International journal

Mitsuhiro Okano, Tazuko Fujiwara, Takaya Higaki, Seiichiro Makihara, Takenori Haruna, Yohei Noda, Kengo Kanai, Shin Kariya, Hiroshi Yasueda, Kazunori Nishizaki

The Journal of allergy and clinical immunology 127 ( 1 ) 277 - 9 2011.1

慢性上気道炎症におけるIL-17A発現の臨床的意義とその制御機構

牧原靖一郎, 岡野光博, 藤原田鶴子, 檜垣貴哉, 野田洋平, 假谷伸, 西崎和則

耳鼻咽喉科免疫アレルギー 28 ( 3 ) 217 - 222 2010.9

Regulation and characterization of IL-17A expression in patients with chronic rhinosinusitis and its relationship with eosinophilic inflammation. Reviewed International journal

Seiichiro Makihara, Mitsuhiro Okano, Tazuko Fujiwara, Shin Kariya, Yohei Noda, Takaya Higaki, Kazunori Nishizaki

The Journal of allergy and clinical immunology 126 ( 2 ) 397 - 400 2010.8

【ステロイドによる局所療法のアップデート】新規鼻噴霧用ステロイド薬の急性鼻副鼻腔炎に対する欧米での評価

牧原靖一郎, 岡野光博

アレルギー・免疫 17 ( 4 ) 591 - 598 2010.3

Authorship：Lead author Language：Japanese Publisher：(株)医薬ジャーナル社

本邦では、リン酸デキサメタゾンなどの全身性ステロイド薬はネブライザーなどの投与に限り副鼻腔炎に対する適応を有するが、鼻噴霧用ステロイド薬は副鼻腔炎に対する適応を有さない。一方、海外ではmometasone furoate(MFNS)やfluticasone propionate(FP)のようなバイオアベイラビリティが低く、局所への効果の強い鼻噴霧用ステロイド薬(intranasal corticosteroids;INCS)は急性副鼻腔炎に対して、抗生剤に上乗せすることで抗生剤単独よりも症状改善をきたすことが示されている。INCSが高用量の場合はさらに効果が増すことも示唆されている。INCS単剤投与の場合は、中等症以下の急性副鼻腔炎に対し、アモキシシリン単剤投与よりも効果が認められた報告もみられる。一方、INCS使用はプラセボと比較し目立った副作用は認められず、高い安全性が示されている。(著者抄録)

Prostaglandin E(2) suppresses staphylococcal enterotoxin-induced eosinophilia-associated cellular responses dominantly through an E-prostanoid 2-mediated pathway in nasal polyps. Reviewed International journal

Mitsuhiro Okano, Tazuko Fujiwara, Takenori Haruna, Shin Kariya, Seiichiro Makihara, Takaya Higaki, Kazunori Nishizaki

The Journal of allergy and clinical immunology 123 ( 4 ) 868 - 74 2009.4

Language：English Publishing type：Research paper (scientific journal) Publisher：MOSBY-ELSEVIER

BACKGROUND: Recent investigations have revealed that staphylococcal enterotoxins (SEs), COX metabolism, or both might participate in the pathogenesis of eosinophilic airway diseases, such as chronic rhinosinusitis with nasal polyposis. OBJECTIVE: We sought to determine whether COX metabolism, especially prostaglandin (PG) E(2), plays a significant role in SE-induced cellular responses in nasal polyps. METHODS: Dispersed nasal polyp cells (DNPCs) were prepared from nasal polyps by means of enzymatic digestion. DNPCs were cultured with SEB in the presence or absence of COX inhibitors (diclofenac and indomethacin) for 72 hours; then the levels of IL-5, IL-13, RANTES, and eotaxin in the supernatants were measured. The effect of PGE(2) on SEB-induced responses by diclofenac-treated DNPCs was examined, especially in terms of receptor specificity. RESULTS: DNPCs produced significant amounts of IL-5, IL-13, and RANTES in response to SEB. COX inhibitors significantly increased the production of these cytokines. The degree of local eosinophilia was significantly and positively correlated with the changes in IL-5 production induced by diclofenac treatment. PGE(2) significantly and dose-dependently inhibited SEB-induced IL-5, IL-13, and RANTES production by diclofenac-treated DNPCs. E-prostanoid (EP) 2 receptor-selective agonist strongly inhibited the production of all 3 cytokines. EP3 and EP4 receptor-selective agonists partially suppressed these responses, whereas EP1 receptor-selective agonist did not. Interestingly, all of the combined treatments with 2 of the 4 EP receptor-selective agonists significantly inhibited the SEB-induced responses by diclofenac-treated DNPCs. CONCLUSIONS: These results suggest that PGE(2) inhibits the pathogenesis of SEB-induced eosinophilic inflammation primarily through the EP2-mediated pathway in patients with chronic rhinosinusitis with nasal polyposis.

DOI： 10.1016/j.jaci.2009.01.047

A case of renal metastasis originating from primary hypopharyngeal and esophageal cancer Reviewed

NOMIYA Shigenobu, MAKIHARA Seiichirou, MATSUMOTO Rie, ORITA Yorihisa, KARIYA Shin, ONODA Tomoo, TOMINAGA Susumu, NISHIZAKI Kazunori

Stomato-pharyngology 20 ( 3 ) 293 - 298 2008

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Japan Society of Stomato-pharyngology

Renal metastasis originating from metachronous development of hypopharyngeal and esophageal cancer is reported. A 60-year-old man had received pharyngolaryngectomy for hypopharyngeal cancer in 2003. He had stomachache in 2005 and a right renal tumor was found with CT and MRI. Percutaneous needle biopsy was performed and histological results showed squamous cell carcinoma. At the same time, squamous cell carcinoma was detected in the esophagus. He had chemotherapy but it was ineffective. This case was thought to be a rare case of metastatic renal cancer arising from multiple primary cancers.

DOI： 10.14821/stomatopharyngology1989.20.293

Other Link： http://search.jamas.or.jp/link/ui/2008358660

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