研究者情報

マスター

アカウント（マスター）

• 氏名

  南場　研一(ナンバ　ケンイチ), ナンバ　ケンイチ

所属（マスター）

• 医学研究院　専門医学系部門　感覚器病学分野

所属（マスター）

• 医学研究院　専門医学系部門　感覚器病学分野

独自項目

syllabus

• 2021, 基本医学研究, Master's Thesis Research in Medical Sciences, 修士課程, 医学院, 眼科、眼疾患、視覚
• 2021, 基本医学総論, Basic Principles of Medicine, 修士課程, 医学院, 眼科、眼疾患、視覚
• 2021, 医学総論, Principles of Medicine, 博士後期課程, 医学院, 眼科、眼疾患、視覚
• 2021, 基盤医学研究, Dissertation Research in Medical Sciences, 博士後期課程, 医学院, 眼科、眼疾患、視覚 Ophthalmology, Ocular diseases, Vision
• 2021, 臨床医学研究, Dissertation Research in Clinical Medicine, 博士後期課程, 医学院, 眼科、眼疾患、視覚

researchmap

プロフィール情報

学位

• 医学博士（北海道大学大学院医学研究科）

プロフィール情報

• 姓

  南場, ナンバ

• 名

  研一, ケンイチ

• ID各種

  201201029207201024

対象リソース

http://kaken.nii.ac.jp/d/r/70333599.ja.html

業績リスト

研究キーワード

• ぶどう膜炎   EAU   実験的自己免疫性網膜ぶどう膜炎   OCH   TLR   糖鎖   グライコミクス   Jα-281ノックアウトマウス   aGalCel   CD1ノックアウトマウス   樹状細胞   α-GC   CD1   NKT細胞   Ja281   グライコブロッティング   ベーチェット病   難治性内眼炎   マイクロサテライト   原田病   アデノウイルス角結膜炎   流行性結膜炎   pooled DNA法   院内感染株   エンドトキシ   コキサンチン   遺伝子   臨床遺伝子   免疫学   臨床   

研究分野

• ライフサイエンス / 眼科学

学歴

• 1995年04月 - 1999年03月   北海道大学大学院医学研究科
• 1986年04月 - 1992年03月   北海道大学医学部

論文

• Adalimumab in Active and Inactive, Non-Infectious Uveitis: Global Results from the VISUAL I and VISUAL II Trials.

  Goto H, Zako M, Namba K, Hashida N, Kaburaki T, Miyazaki M, Sonoda KH, Abe T, Mizuki N, Kamoi K, Brézin AP, Dick AD, Jaffe GJ, Nguyen QD, Inomata N, Kwatra NV, Camez A, Song AP, Kron M, Tari S, Ohno S

  Ocular immunology and inflammation 1 - 11 2018年07月 [査読有り][通常論文]
  
• Two cases of cytomegalovirus panuveitis in immunocompetent patients

  Masato Sakai, Hiroshi Takase, Kenichi Namba, Kazuomi Mizuuchi, Daiju Iwata, Susumu Ishida

  American Journal of Ophthalmology Case Reports 10 189 - 191 2018年06月01日 [査読有り][通常論文]
   

  Purpose: To report two cases of panuveitis in immunocompetent patients in which cytomegalovirus was involved. Observation: Case 1 was a 46-year-old man who had a history of recurrent anterior chamber inflammations in his left eye. After Nd:YAG laser posterior capsulotomy, he developed panuveitis with vitreous haze and periphlebitis. Polymerase chain reaction (PCR) examination revealed the presence of cytomegalovirus (CMV) DNA in the anterior chamber (AC). He responded well to a series of intravitreal injections of ganciclovir (GCV). Case 2 was a 63-year-old woman who had a history of recurrent anterior uveitis in her left eye. Two years after cataract surgery, AC inflammation, diffuse vitreous haze, and periphlebitis had developed. CMV DNA was detected in the AC. Intravitreal injections of GCV and oral valganciclovir were administered, and ocular inflammation finally improved. Conclusions: and importance: We experienced two cases of CMV panuveitis in immunocompetent adults, both of which responded well to anti-viral therapies.
• Cytopathologic findings of cell block materials from the vitreous: Diagnostic distinction between intraocular lymphoma and non-lymphomatous diseases

  Hiromi Kanno-Okada, Emi Takakuwa, Yoshiaki Tagawa, Satoru Kase, Kanako C. Hatanaka, Yutaka Hatanaka, Kenichi Namba, Tomoko Mitsuhashi, Yoshihiro Matsuno

  PATHOLOGY INTERNATIONAL 67 7 342 - 349 2017年07月 [査読有り][通常論文]
   

  Intraocular lymphoma is a rare neoplasm that occurs only in the eyes and/or central nervous system. Diagnosis of intraocular lymphoma is difficult because its clinical manifestations mimic chronic uveitis. Pathological examination of the vitreous is one of the main diagnostic tools for intraocular lymphoma, but this is challenging due to the sparse cellularity and specimen degeneration. Here, we reviewed 33 cell block preparations from vitreous perfusion fluid in order to examine the significance of cytopathological findings for differential diagnosis using vitreous samples. The cases comprised 12 intraocular lymphomas and 21 non-lymphomatous diseases. Cytologically, vitreous samples from non-lymphoma cases showed lower cellularity than the lymphoma cases. Whereas vitreous material from cases with infectious endophthalmitis showed prominent neutrophilic infiltration, material from sarcoidosis cases showed infiltration of small lymphoid cells, especially CD4-positive T cells. On the other hand, lymphoma cases showed higher cellularity, with large, irregular and atypical lymphoid cells, frequent necrotic cells in the background, and less pronounced neutrophil infiltration. Immunocytochemically, 11 of the 12 lymphoma cases were of the B-cell phenotype and the remaining case was of the T/NK-cell phenotype. In conclusion, careful cytopathological examination or immunocytochemistry of vitreous material facilitates appropriate diagnosis of intraocular lymphoma.
• A Novel Single-Strand RNAi Therapeutic Agent Targeting the (Pro)renin Receptor Suppresses Ocular Inflammation

  Atsuhiro Kanda, Erdal Tan Ishizuka, Atsushi Shibata, Takahiro Matsumoto, Hidekazu Toyofuku, Kousuke Noda, Kenichi Namba, Susumu Ishida

  MOLECULAR THERAPY-NUCLEIC ACIDS 7 116 - 126 2017年06月 [査読有り][通常論文]
   

  The receptor-associated prorenin system (RAPS) refers to the pathogenic mechanism whereby prorenin binding to the (pro) renin receptor [(P) RR] dually activates the tissue reninangiotensin system (RAS) and RAS-independent intracellular signaling. Here we revealed significant upregulation of prorenin and soluble (P) RR levels in the vitreous fluid of patients with uveitis compared to non-inflammatory controls, together with a positive correlation between these RAPS components and monocyte chemotactic protein-1 among several upregulated cytokines. Moreover, we developed a novel single-strand RNAi agent, proline-modified short hairpin RNA directed against human and mouse (P) RR [(P) RR-PshRNA], and we determined its safety and efficacy in vitro and in vivo. Application of (P) RR-PshRNA in mice caused significant amelioration of acute (uveitic) and chronic (diabetic) models of ocular inflammation with no apparent adverse effects. Our findings demonstrate the significant implication of RAPS in the pathogenesis of human uveitis and the potential usefulness of (P) RR-PshRNA as a therapeutic agent to reduce ocular inflammation.
• Evaluating the efficacy of epinastine ophthalmic solution using a conjunctivitis allergen challenge model in patients with birch pollen allergic conjunctivitis

  Yoshiaki Tagawa, Kenichi Namba, Yumi Nakazono, Daiju Iwata, Susumu Ishida

  ALLERGOLOGY INTERNATIONAL 66 2 338 - 343 2017年04月 [査読有り][通常論文]
   

  Background: The efficacy of epinastine 0.05% ophthalmic solution for pollen allergic conjunctivitis has already been shown in a conjunctival allergen challenge (CAC) test using cedar pollen as a challenge. The present study investigated the efficacy of this solution against birch pollen conjunctivitis in a CAC test. Methods: Ten adult subjects (eight males and two females) with asymptomatic birch pollen conjunctivitis were enrolled in this study. The average age of the subjects was 41.1 years. This study was conducted during a period without birch pollen dispersion. In each subject, the epinastine 0.05% ophthalmic solution was instilled in one eye, and an artificial tear fluid was instilled in the fellow eye in a double-blind manner. Five minutes or 4 h after the drug instillation, both eyes were challenged with an optimal concentration of birch pollen, and ocular itching and conjunctival hyperemia were then graded. Tears were collected before the drug instillation and 20 min after the pollen challenge, and the histamine level was measured. Results: The ocular itching scores and palpebral conjunctival hyperemia scores of the epinastine-treated eyes were significantly lower than those of the contralateral control eyes when the eyes were pretreated with the drug 4 h before the CAC. There was a significant correlation between the tear histamine level and mean ocular itching score of three time points (3, 5 and 10 min) following the CAC in the control eyes but not the epinastine-treated eyes. Conclusions: Epinastine is effective in suppressing ocular itching and conjunctival hyperemia in birch pollen conjunctivitis. Copyright (C) 2017, Japanese Society of Allergology. Production and hosting by Elsevier B.V.
• Japanese guidelines for allergic conjunctival diseases 2017

  Etsuko Takamura, Eiichi Uchio, Nobuyuki Ebihara, Shigeaki Ohno, Yuichi Ohashi, Shigeki Okamoto, Naoki Kumagai, Yoshiyuki Satake, Jun Shoji, Yayoi Nakagawa, Kenichi Namba, Kazumi Fukagawa, Atsuki Fukushima, Hiroshi Fujishima

  ALLERGOLOGY INTERNATIONAL 66 2 220 - 229 2017年04月 [査読有り][通常論文]
   

  The definition, classification, pathogenesis, test methods, clinical findings, criteria for diagnosis, and therapies of allergic conjunctival disease are summarized based on the Guidelines for Clinical Management of Allergic Conjunctival Disease (Second Edition) revised in 2010. Allergic conjunctival disease is defined as "a conjunctival inflammatory disease associated with a Type I allergy accompanied by some subjective or objective symptoms." Allergic conjunctival disease is classified into allergic conjunctivitis, atopic keratoconjunctivitis, vernal keratoconjunctivitis, and giant papillary conjunctivitis. Representative subjective symptoms include ocular itching, hyperemia, and lacrimation, whereas objective symptoms include conjunctival hyperemia, swelling, folliculosis, and papillae. Patients with vernal keratoconjunctivitis, which is characterized by conjunctival proliferative changes called giant papilla accompanied by varying extents of corneal lesion, such as corneal erosion and shield ulcer, complain of foreign body sensation, ocular pain, and photophobia. In the diagnosis of allergic conjunctival diseases, it is required that type I allergic diathesis is present, along with subjective and objective symptoms accompanying allergic inflammation. The diagnosis is ensured by proving a type I allergic reaction in the conjunctiva. Given that the first-line drug for the treatment of allergic conjunctival disease is an antiallergic eye drop, a steroid eye drop will be selected in accordance with the severity. In the treatment of vernal keratoconjunctivitis, an immunosuppressive eye drop will be concomitantly used with the abovementioned drugs. Copyright (C) 2016, Japanese Society of Allergology. Production and hosting by Elsevier B.V.
• Investigation of the association between IL10 gene polymorphisms and Vogt-Koyanagi-Harada disease in a Japanese population

  Kaori Higashi, Akira Meguro, Masaki Takeuchi, Takahiro Yamane, Nobuyoshi Kitaichi, Yukihiro Horie, Kenichi Namba, Shigeaki Ohno, Kumiko Nakao, Taiji Sakamoto, Tsutomu Sakai, Hiroshi Tsuneoka, Hiroshi Keino, Annabelle A. Okada, Atsunobu Takeda, Takako Fukuhara, Hisashi Mashimo, Nobuyuki Ohguro, Shinichirou Oono, Hiroshi Enaida, Satoshi Okinami, Nobuhisa Mizuki

  OPHTHALMIC GENETICS 38 2 187 - 189 2017年03月 [査読有り][通常論文]
  
• Steroid-Sparing Effect of 0.1% Tacrolimus Eye Drop for Treatment of Shield Ulcer and Corneal Epitheliopathy in Refractory Allergic Ocular Diseases

  Dai Miyazaki, Atsuki Fukushima, Yuichi Ohashi, Nobuyuki Ebihara, Eiichi Uchio, Shigeki Okamoto, Jun Shoji, Etsuko Takamura, Yayoi Nakagawa, Kenichi Namba, Hiroshi Fujishima

  OPHTHALMOLOGY 124 3 287 - 294 2017年03月 [査読有り][通常論文]
   

  Purpose: To evaluate the effects of 0.1% topical tacrolimus alone or in combination with steroids for the treatment of shield ulcers and corneal epitheliopathy in patients with refractory allergic ocular diseases. Design: Open cohort study. Participants: Patients with refractory allergic conjunctivitis epitheliopathy, shield ulcers, or corneal plaques (N = 791). Methods: The 791 patients were treated with topical tacrolimus alone or in combination with topical or oral steroids. The effectiveness of the treatments was determined by a corneal epitheliopathy score during the 3-month follow-up period. The clinical signs were rated on a 4-grade scale. Corneal epitheliopathy with no corneal staining was graded as 0, and shield ulcers or plaques were graded as 3, the highest grade. The effects of tacrolimus with and without topical steroids on the epitheliopathy scores were assessed after adjustments for the severity of the clinical signs and characteristics. Main Outcome Measures: Changes in the corneal epitheliopathy score. Results: Adjusted mean epitheliopathy score at the baseline was 1.73 (95% confidence interval [CI], 1.65-1.81) for patients treated with tacrolimus alone, and this was significantly reduced by -0.93 at 1 month. The reduction of the score by topical and oral steroids was -0.02 for fluorometholone, 0.02 for betamethasone, and -0.02 for oral steroids, and these reductions were not significant compared with the reduction effect of topical tacrolimus alone at -0.93. The 238 patients with shield ulcer (score 3) were analyzed with adjustments, and the mean epitheliopathy score at 1 month was reduced to 1.38 with tacrolimus alone (95% CI, 1.24-1.51), 1.41 (95% CI, 1.26-1.56) with adjuvant fluorometholone, and 1.46 (95% CI, 1.32-1.61) with adjuvant betamethasone. No significant difference was observed in the adjunctive topical steroids. The presence of severe palpebral conjunctival symptoms, including giant papillae, was a significant resisting factor for topical tacrolimus. Conclusions: The significant effects of topical tacrolimus alone on shield ulcers and corneal epitheliopathy suggest that it may be used without the need for steroids. (C) 2016 by the American Academy of Ophthalmology.
• Early post-treatment choroidal thickness to alert sunset glow fundus in patients with Vogt-Koyanagi- Harada disease treated with systemic corticosteroids

  Kiriko Hirooka, Wataru Saito, Kenichi Namba, Kazuomi Mizuuchi, Daiju Iwata, Yuki Hashimoto, Susumu Ishida

  PLOS ONE 12 2 e0172612  2017年02月 [査読有り][通常論文]
   

  Purpose To determine if early post-treatment central choroidal thickness (CCT) changes can predict sunset glow fundus (SGF) development in patients with Vogt-Koyanagi-Harada (VKH) disease treated using systemic corticosteroids. Methods This retrospective case series included 39 eyes of 21 treatment-naive patients with acute VKH disease who could be followed up for more than 12 months after systemic corticosteroid therapy. The eyes were divided into two groups according to whether SGF was present or absent at 12 months (9 eyes of 5 patients versus 30 eyes of 16 patients, respectively). Using enhanced depth imaging optical coherence tomography, CCT values were measured before treatment, then at 1 week and 1 and 3 months after treatment in both groups and compared between the two groups. Results Development of SGF was found 4-11 months after treatment. Mean post-treatment CCT decreased significantly at all examinations compared with baseline in both groups, along with resolution of serous retinal detachment. One week after treatment, mean CCT was significantly higher in eyes with SGF than in those without (P = 0.024). SGF was present at 12 months in 9 of 22 eyes with CCT values > 410 mu m at 1 week after starting treatment, in contrast with none of 17 eyes with CCT <= 410 mu m at this time (P = 0.003). Conclusions The current study suggested the potential validity of early post-treatment CCT as a feasible index to alert future progression to SGF in patients with VKH disease treated using systemic corticosteroids.
• HLA-B51 Carriers are Susceptible to Ocular Symptoms of Behçet Disease and the Association between the Two Becomes Stronger towards the East along the Silk Road: A Literature Survey.

  Horie Y, Meguro A, Ohta T, Lee EB, Namba K, Mizuuchi K, Iwata D, Mizuki N, Ota M, Inoko H, Ishida S, Ohno S, Kitaichi N

  Ocular immunology and inflammation 25 1 37 - 40 2017年 [査読有り][通常論文]
   

  Purpose: Behcet disease (BD) is predominantly found between East Asia and the Mediterranean basin along the historic Silk Road. HLA-B51 is known to be strongly associated with BD. We investigated the association between HLA-B51 and the ocular manifestations of BD among various ethnic groups. Methods: A literature survey was conducted, and 18 articles written in English were reviewed. Results: A strong correlation was found between HLA-B51 and ocular lesions in the entire cohort discussed in the reviewed articles (OR = 1.76, p = 0.000057). HLA-B51 was shown to have a strong association with ocular manifestations of BD patients in East-Eurasian (OR = 2.40, p = 0.0030) and Middle-Eurasian (OR = 1.87, p = 0.0045), but not in West-Eurasian (OR = 1.28, p = 0.35) areas. This correlation seemed to become stronger towards the east. Conclusions: A meta-analysis showed that the correlation became stronger towards the east along the Silk Road. The study results may facilitate understanding of the etiology and characteristics of BD.
• Serial Frequencies and Clinical Features of Uveitis in Hokkaido, Japan

  Daiju Iwata, Kazuomi Mizuuchi, Koki Aoki, Yukihiro Horie, Satoru Kase, Kenichi Namba, Shigeaki Ohno, Susumu Ishida, Nobuyoshi Kitaichi

  OCULAR IMMUNOLOGY AND INFLAMMATION 25 sup1 S15 - S18 2017年 [査読有り][通常論文]
   

  Purpose: Environmental and lifestyle changes influence the clinical features of uveitis. This study reviewed the epidemiologic trends of uveitis in the Japanese population.Methods: A retrospective review of the past 80 years of reports from Hokkaido University Hospital.Results: In the 1930s, tuberculosis accounted for 46% and syphilitic uveitis for 31% of cases. The frequency of these diseases decreased to 12% in the 1950s; 8% in 1969; 0.6% in the 1990s; and 0.8% in the 2000s, while the rate of non-infectious uveitis increased. The three most common specific diagnoses were: sarcoidosis, Vogt-Koyanagi-Harada disease, and Behcet disease. Although Behcet disease was the most frequent non-infectious uveitis until the 1980s, sarcoidosis is now the most frequent cause of newly diagnosed non-infectious uveitis.Conclusions: The etiology of uveitis has changed with the times. Tubercular and syphilitic cases have greatly decreased, and sarcoidosis is the most frequent type of uveitis today.
• Choroidal circulation impairment during the anterior recurrence of Vogt-Koyanagi-Harada disease confirmed with indocyanine green angiography and laser speckle flowgraphy

  Yuko Takemoto, Kenichi Namba, Kazuomi Mizuuchi, Daiju Iwata, Tomoe Uno, Shigeaki Ohno, Kiriko Hirooka, Yuki Hashimoto, Wataru Saito, Kazuhisa Sugiyama, Susumu Ishida

  ACTA OPHTHALMOLOGICA 94 7 E629 - E636 2016年11月 [査読有り][通常論文]
   

  PurposeTo assess choroidal inflammation-related circulatory changes associated with the anterior recurrence of Vogt-Koyanagi-Harada (VKH) disease, using indocyanine green angiography (ICGA) and laser speckle flowgraphy (LSFG). MethodsThis retrospective case series included 17 eyes of 11 patients with VKH disease showing recurrent inflammatory findings in the anterior, but not posterior, segment (i.e. anterior recurrence). Indocyanine green angiography (ICGA) and LSFG were performed at the time of recurrence and one month after the initiation of corticosteroid therapy. The number and total area of hypofluorescent dark dots (HDDs) on ICGA were independently counted by three physicians and measured with ImageJ, respectively. Mean blur rate (MBR), a quantitative index of relative blood flow velocity, was calculated via the LSFG Analyzer software. ResultsHypofluorescent dark dots (HDDs) were identified on ICGA in 13 of 17 eyes (76%) with the anterior recurrence of VKH disease. The number and total area of HDDs significantly decreased from 203101 dots to 59 +/- 51 dots and from 48789 +/- 24251 pixels to 15664 +/- 13254 pixels, respectively. The change ratio of MBR significantly increased by 17.9 +/- 16.3% after the treatment. Importantly, there was no significant association between the change ratios of HDDs and MBR. ConclusionsThese findings on LSFG and ICGA clearly demonstrated subclinical involvement as well as post-treatment improvement of choroidal circulation impairment due to granulomatous inflammation in eyes with the anterior recurrence of VKH disease. The present data suggest the validity of using these two examinations, capable of detecting different circulatory changes, in the management of recurrent VKH disease.
• Choroidal thickening prior to anterior recurrence in patients with Vogt-Koyanagi-Harada disease

  Yoshiaki Tagawa, Kenichi Namba, Kazuomi Mizuuchi, Yuko Takemoto, Daiju Iwata, Tomoe Uno, Takako Fukuhara, Kiriko Hirooka, Nobuyoshi Kitaichi, Shigeaki Ohno, Susumu Ishida

  BRITISH JOURNAL OF OPHTHALMOLOGY 100 4 473 - 477 2016年04月 [査読有り][通常論文]
   

  Aim To assess choroidal thickness changes associated with anterior segment recurrences in patients with Vogt-Koyanagi-Harada (VKH) disease using enhanced depth imaging optical coherence tomography (EDI-OCT). Methods EDI-OCT images were obtained periodically from 11 patients with VKH disease (22 eyes) who were followed-up due to anterior segment recurrences. Subfoveal choroidal thickness (SCT) values at the following stages were evaluated: (1) during the remission phase, (2) 1 month before detecting the anterior recurrence, (3) during the anterior recurrence and (4) after systemic prednisolone (PSL) treatment leading to remission. In comparison with SCT values in remission as baseline, the changing ratios of SCT were statistically analysed at subsequent three stages. Results The average of the SCT changing ratios compared with the remission phase significantly increased to 1.45 +/- 0.11 during anterior segment recurrences (p=0.00044) lacking any funduscopic signs of posterior involvement. Interestingly, the average SCT ratio 1 month before detecting the recurrence had already increased to 1.30 +/- 0.08 (p=0.002). After the PSL treatment, the ratio of SCT recovered to 0.95 +/- 0.03, which was equivalent to the remission level. However, in patients with their remission SCT values less than 240 mm, the SCT ratio did not increase significantly at any time points evaluated. Conclusions The choroid in eyes with VKH disease thickened in association with the anterior segment recurrence, and this thickening was observed prior to the recurrence. EDI-OCT may be useful for detecting latent choroidal inflammation in VKH disease, whereas it may not for patients with the relatively thin choroid.
• Diagnostic efficacy of cell block method for vitreoretinal lymphoma

  Satoru Kase, Kenichi Namba, Daiju Iwata, Kazuomi Mizuuchi, Nobuyoshi Kitaichi, Yoshiaki Tagawa, Hiromi Okada-Kanno, Yoshihiro Matsuno, Susumu Ishida

  DIAGNOSTIC PATHOLOGY 11 29  2016年03月 [査読有り][通常論文]
   

  Background: Vitreoretinal lymphoma (VRL) is a life- and sight-threatening disorder. The aim of this study was to analyze the usefulness of the cell block method for diagnosis of VRL. Methods: Sixteen eyes in 12 patients with VRL, and 4 eyes in 4 patients with idiopathic uveitis presenting with vitreous opacity were enrolled in this study. Both undiluted vitreous and diluted fluids were isolated during micro-incision vitrectomy. Cell block specimens were prepared in 19 eyes from diluted fluid containing shredding vitreous. These specimens were then submitted for HE staining as well as immunocytological analyses with antibodies against the B-cell marker CD20, the T-cell marker CD3, and cell proliferation marker Ki67. Conventional smear cytology was applied in 14 eyes with VRL using undiluted vitreous samples. The diagnosis of VRL was made based on the results of cytology, concentrations of interleukin (IL)-10 and IL-6 in undiluted vitreous, and immunoglobulin heavy chain gene rearrangement analysis. Results: Atypical lymphoid cells were identified in 14 out of 15 cell block specimens of VRL (positive rate: 93.3 %), but in 5 out of 14 eyes in conventional smear cytology (positive rate: 35.7 %). Atypical lymphoid cells showed immunoreactivity for CD20 and Ki67. Seven cell block specimens were smear cytology-negative and cell block-positive. The cell block method showed no atypical lymphoid cells in any patient with idiopathic uveitis. Conclusions: Cell block specimens using diluted vitreous fluid demonstrated a high diagnostic sensitivity and a low pseudo-positive rate for the cytological diagnosis of VRL. The cell block method contributed to clear differentiation between VRL and idiopathic uveitis with vitreous opacity.
• A Case of Severe Panuveitis Associated with Psoriasis Vulgaris Successfully Treated with Infliximab

  Yuri Sakurai, Kenichi Namba, Kazuomi Mizuuchi, Toshihumi Nomura, Susumu Ishida

  Case Reports in Ophthalmology 7 1 191 - 194 2016年 [査読有り][通常論文]
   

  Purpose: Uveitis associated with psoriasis vulgaris is usually seen as an anterior segment inflammation, and it is very rare that the inflammation extends to the posterior segment. We herein report a case of severe panuveitis associated with psoriasis vulgaris presenting as retinal neovascularization, leading to vitreous hemorrhages that were successfully treated with infliximab (IFX). Case Report: A 27-year-old male with psoriasis vulgaris was referred to our hospital due to prolonged severe uveitis OU. He showed a severe anterior chamber inflammation with fibrin formation and total posterior iris synechia OU. With topical corticosteroid treatment, these conditions were relieved for a short time however, the intraocular inflammation was exacerbated with vitreous hemorrhages caused by retinal neovascularization OS. After the administration of IFX therapy, the intraocular inflammation and retinal neovascularization was resolved, and so far, no severe recurrences have been seen for 3 years with the therapy. Conclusion: When we see patients with severe panuveitis associated with psoriasis extending to the posterior segment, IFX treatment may be a good therapeutic option.
• Ocular Behçet's disease is less complicated with allergic disorders. A nationwide survey in Japan.

  Horie Y, Kitaichi N, Hijioka K, Sonoda KH, Saishin Y, Kezuka T, Goto H, Takeuchi M, Nakamura S, Kimoto T, Shimakawa M, Kita M, Sugita S, Mochizuki M, Hori J, Iwata M, Shoji J, Fukuda M, Kaburaki T, Numaga J, Kawashima H, Fukushima A, Joko T, Takai N, Ozawa Y, Meguro A, Mizuki N, Namba K, Ishida S, Ohno S

  Clinical and experimental rheumatology 34 6 Suppl 102 111 - 114 2016年 [査読有り][通常論文]
   

  Objective. Behçet's disease (BD) is a systemic inflammatory disorder polarised to the Th1 and Th17 immune systems. Allergic diseases are polarised to the Th2 immune system. The aim of the present study is to investigate the prevalence of allergic diseases in patients who have BD. Methods. The study involved a largescale interview survey of Japanese patients with BD at 21 institutes of ophthalmology 353 patients (255 males and 98 females) were recruited for this study. We analysed the history of allergic diseases such as atopic dermatitis (AD), allergic rhinitis (AR), bronchial asthma (BA) and drug/food allergies (FA). Results. Oral aphthous ulcers, ocular lesions, skin lesions, genital ulcers, arthritis, neurological lesions, intestinal lesions, deep vein thrombosis and epididymitis were reported in 95.8%, 98.6%, 72.5%, 44.8%, 13.9%, 6.8%, 6.2%, 3.7% and 1.4% of the patients, respectively. It was also reported that 73 patients (20.7%) had histories of allergic diseases: AD (5 cases, 1.4%), AR (36 cases, 10.2%), BA (19 cases, 5.4%) and FA (30 cases, 8.5%). This percentage was significantly lower than in a survey that Japan's Ministry of Health, Labour and Welfare conducted for healthy population (47.6%) (odds ratio = 0.29, 95% confidence interval = 0.22-0.38, p=4.9×10-22). Frequencies of posterior/pan-uveitis, relatively severe ocular findings, and visual prognosis were not affected by a history of allergic diseases in BD. Conclusion. Patients with BD had fewer complications from allergic diseases than did the entire population of Japan.
• Significant role of the choroidal outer layer during recovery from choroidal thickening in Vogt-Koyanagi-Harada disease patients treated with systemic corticosteroids

  Kiriko Hirooka, Wataru Saito, Kenichi Namba, Kazuomi Mizuuchi, Daiju Iwata, Yuki Hashimoto, Susumu Ishida

  BMC OPHTHALMOLOGY 15 181  2015年12月 [査読有り][通常論文]
   

  Background: Which of the choroidal layers suffers the most extensive morphological changes during the course of Vogt-Koyanagi-Harada (VKH) disease is still unknown. The aim of this study was to investigate the relationship between total thickness and the thickness of inner or outer layers in the choroid during systemic corticosteroid therapy in patients with VKH disease. Methods: This retrospective case series included 15 eyes of 10 patients with treatment-naive VKH disease (4 men and 6 women; mean age, 41.4 +/- 14.7 years) received systemic corticosteroid therapy. Whole, inner, and outer choroidal thickness was measured manually at 1 week and at 1 and 3 months after initiation of systemic corticosteroid therapy using enhanced depth imaging optical coherence tomography. The mean thickness values of the layers were compared at each stage. Results: Compared with the 1-week baseline, the mean whole and outer choroidal layer thicknesses were significantly lower at 1 (P = 0.008 and 0.03, respectively) and 3 months (P = 0.008 and 0.02, respectively), whereas the inner layer did not significantly thin. Importantly, there was a significant positive correlation between the rates of change of whole and outer layer thickness from 1 week to 3 months (R = 0.9312, P < 0.0001), but not between the rates of whole and inner layer thickness changes. Conclusions: The thinning of total choroidal thickness observed after treatment with corticosteroids strongly correlated with outer layer thinning, suggesting that the choroidal outer layer is the primary target in acute-stage VKH disease.
• A case of tuberculous endophthalmitis successfully treated with vitrectomy followed by antituberculous agents

  Keitaro Hase, Kenichi Namba, Wataru Saito, Shigeaki Ohno, Susumu Ishida

  Journal of Ophthalmic Inflammation and Infection 5 1 14  2015年12月01日 [査読有り][通常論文]
   

  Background: Tuberculous endophthalmitis is very rare with only 18 reports published worldwide and only a few cases in Japan. We report a case of tuberculous endophthalmitis successfully treated with vitrectomy followed by antituberculous agents. Findings: An 81-year-old man was referred to us due to the exacerbation of vitreous opacity on his left eye(OS) after he had received the corticosteroid therapy. His best corrected visual acuity was light perception OS, and he had severe intraocular inflammation with fibrin formation in the anterior chamber and dense vitreous opacity. A chest CT showed miliary nodules indicating miliary tuberculosis, and pars plana vitrectomy was performed. Intraoperative observation showed that the vitreous cavity was filled by fibrin, and large elevated subretinal yellow-white lesions were present at the mid-periphery. The patient immediately received triple antituberculous agents orally, and Mycobacterium tuberculosis was detected in vitreous fluids. The intraocular inflammation gradually decreased, and the subretinal mass regressed within 2 weeks. Conclusions: We encountered a case of tuberculous endophthalmitis successfully treated with vitrectomy followed by antituberculous agents. If endophthalmitis is suspected in a patient with systemic tuberculosis infection, prompt vitrectomy along with the administration of antituberculous agents may be necessary.
• Relationship between choroidal blood flow velocity and choroidal thickness during systemic corticosteroid therapy for Vogt-Koyanagi-Harada disease

  Kiriko Hirooka, Wataru Saito, Kenichi Namba, Yuko Takemoto, Kazuomi Mizuuchi, Tomoe Uno, Yoshiaki Tagawa, Yuki Hashimoto, Susumu Ishida

  GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY 253 4 609 - 617 2015年04月 [査読有り][通常論文]
   

  To investigate the relationship between circulation hemodynamics and morphology in the choroid during systemic corticosteroid therapy for patients with Vogt-Koyanagi-Harada (VKH) disease. This retrospective case series includes 18 eyes of nine patients with VKH disease (two men and seven women; average age, 40.8 years) who received systemic corticosteroid therapy. Laser speckle flowgraphy (LSFG) and enhanced-depth imaging optical coherence tomography (EDI-OCT) were performed before treatment and at 1 week and 1 and 3 months after treatment. The average values of the mean blur rate (MBR) at the macula and the central choroidal thickness (CCT) were compared at each stage. The changing rates of the average MBR significantly increased at all examinations after the start of treatment compared with the pre-treatment value with resolution of serous retinal detachment (SRD) (P = 0.0002 for all). The CCT decreased significantly at all examinations after the start of treatment compared with the pre-treatment value (P = 0.0002 for all). Changes in MBR and CCT during the 3-month follow-up period correlated significantly (R = -0.5913, P = 0.0097). The best-corrected visual acuity at pre-treatment correlated significantly with the changing rate of the MBR from 0 to 3 months (R = 0.5944, P = 0.0093) but not with CCT. Our data suggest that circulatory disturbances and increased thickness of the choroid relate to the pathogenesis of VKH disease with link mutually. LSFG is useful as an index for evaluating the choroiditis activity of VKH disease as well as EDI-OCT.
• Acute Zonal Occult Outer Retinopathy in Japanese Patients: Clinical Features, Visual Function, and Factors Affecting Visual Function

  Saho Saito, Wataru Saito, Michiyuki Saito, Yuki Hashimoto, Shohei Mori, Kousuke Noda, Kenichi Namba, Susumu Ishida

  PLOS ONE 10 4 e0125133  2015年04月 [査読有り][通常論文]
   

  Purpose To evaluate the clinical features and investigate their relationship with visual function in Japanese patients with acute zonal occult outer retinopathy (AZOOR). Methods Fifty-two eyes of 38 Japanese AZOOR patients (31 female and 7 male patients; mean age at first visit, 35.0 years; median follow-up duration, 31 months) were retrospectively collected: 31 untreated eyes with good visual acuity and 21 systemic corticosteroid-treated eyes with progressive visual acuity loss. Variables affecting the logMAR values of best-corrected visual acuity (BCVA) and the mean deviation (MD) on Humphrey perimetry at initial and final visits were examined using multiple stepwise linear regression analysis. Results In untreated eyes, the mean MD at the final visit was significantly higher than that at the initial visit (P = 0.00002). In corticosteroid-treated eyes, the logMAR BCVA and MD at the final visit were significantly better than the initial values (P = 0.007 and P = 0.02, respectively). The final logMAR BCVA was 0.0 or less in 85% of patients. Variables affecting initial visual function were moderate anterior vitreous cells, myopia severity, and a-wave amplitudes on electroretinography; factors affecting final visual function were the initial MD values, female sex, moderate anterior vitreous cells, and retinal atrophy. Conclusions Our data indicated that visual functions in enrolled patients significantly improved spontaneously or after systemic corticosteroids therapy, suggesting that Japanese patients with AZOOR have good visual outcomes during the follow-up period of this study. Furthermore, initial visual field defects, gender, anterior vitreous cells, and retinal atrophy affected final visual functions in these patients.
• Single center study on ethnic and clinical features of Behcet's disease in Moscow, Russia

  Anton Lennikov, Zemfira Alekberova, Regina Goloeva, Nobuyoshi Kitaichi, Lev Denisov, Kenichi Namba, Mitsuhiro Takeno, Yoshiaki Ishigatsubo, Nobuhisa Mizuki, Eugeny Nasonov, Susumu Ishida, Shigeaki Ohno

  CLINICAL RHEUMATOLOGY 34 2 321 - 327 2015年02月 [査読有り][通常論文]
   

  For the purpose of investigating Behcet's disease (BD) in Russia, 250 consecutive patients (177 men and 73 women) diagnosed with BD between 1990 and 2010 at the Research Institute of Rheumatology, Russian Academy of Medical Sciences in Moscow were enrolled in this study. The ethnic backgrounds of the patients were reported as follows: 23.2 % (58 cases) from Russia, 12.8 % (32 cases) from Azerbaijan, 14.4 % (36 cases) from Armenia, 8.8 % (22 cases) from Chechnya, and 21.6 % (55 cases) from Dagestan. The remaining 19.2 % (48 cases) were from other regions or of unknown origin. More than half (57.6 %) of the Behcet's disease patients originated from Central Asia, specifically Azerbaijan, Armenia, Chechnya, and Dagestan. The mean age at disease onset was 31.5 +/- 9.38 (13-60) years old, and the most typical initial manifestations were oral aphthous ulcers. Patients aged 20-39 years old were more commonly affected and displayed a wide clinical spectrum of the disease, with varieties of severe internal organ involvement. The manifestations observed throughout the course of the disease included oral aphthous ulcers (100 %), various cutaneous lesions (88.8 %), genital ulcers (81.2 %), and ocular lesions (54.0 %). Besides these, many organs/systems were implicated in patient cases, namely joint (53.2 %), vascular (25.2 %), neurological (8.0 %), gastrointestinal (25.2 %), and cardiac (5.6 %) systems. Involvements of ocular (p < 0.01) and skin (p < 0.01) lesions were more frequent in men than in women. HLA-B51 and HLA-A26 typing was performed in 127 patients and 508 healthy controls. HLA-B51 was found in 63.0 % of BD patients compared to 20.7 % of the healthy control subjects (p < 0.001), and HLA-A26 was present in 11.3 % of BD patients and 18.9 % of the control group. This study shows the presence of BD in Russia, and it is suggested that its prevalence in Central Asian people is much higher than that in White Russian.
• A Major Review: Current Aspects of Ocular Behçet's Disease in Japan.

  Namba K, Goto H, Kaburaki T, Kitaichi N, Mizuki N, Asukata Y, Fujino Y, Meguro A, Sakamoto S, Shibuya E, Yokoi K, Ohno S

  Ocular immunology and inflammation 23 Suppl 1 S1 - 23 2015年 [査読有り][通常論文]
  
• A case of mature natural killer-cell neoplasm manifesting multiple choroidal lesions: Primary intraocular natural killer-cell lymphoma

  Yoshiaki Tagawa, Reiki Ogasawara, Hiromi Kanno, Susumu Ishida, Kenichi Namba

  Case Reports in Ophthalmology 6 3 380 - 384 2015年 [査読有り][通常論文]
   

  Purpose: Natural killer (NK) cell neoplasm is a rare disease that follows an acute course and has a poor prognosis. It usually emerges from the nose and appears in the ocular tissue as a metastasis. Herein, we describe a case of NK-cell neoplasm in which the eye was considered to be the primary organ. Case: A 50-year-old female displayed bilateral anterior chamber cells, vitreous opacity, bullous retinal detachment, and multiple white choroidal mass lesions. Although malignant lymphoma or metastatic tumor was suspected, various systemic examinations failed to detect any positive results. A vitrectomy was performed OS however, histo-cytological analyses from the vitreous sample showed no definite evidence of malignancy, and IL-10 concentration was low. Enlarged choroidal masses were fused together. Three weeks after the first visit, the patient suddenly developed an attack of fever, night sweat, and hepatic dysfunction, and 5 days later, she passed away due to multiple organ failure. Im-munohistochemisty and in situ hybridization revealed the presence of atypical cells positive for CD3, CD56, and Epstein-Barr virus-encoded RNAs, resulting in the diagnosis of NK-cell neoplasm. With the characteristic clinical course, we concluded that this neoplasm was a primary intraocular NK-cell lymphoma. Conclusions: This is the first report to describe primary intraocular NK-cell neoplasm. When we encounter atypical choroidal lesions, we should consider the possibility of NK-cell lymphoma, even though it is a rare disease.
• Development and validation of new diagnostic criteria for acute retinal necrosis

  Hiroshi Takase, Annabelle A. Okada, Hiroshi Goto, Nobuhisa Mizuki, Kenichi Namba, Nobuyuki Ohguro, Koh-Hei Sonoda, Makoto Tomita, Hiroshi Keino, Takeshi Kezuka, Reo Kubono, Kazuomi Mizuuchi, Etsuko Shibuya, Hiroyuki Takahashi, Ryoji Yanai, Manabu Mochizuki

  JAPANESE JOURNAL OF OPHTHALMOLOGY 59 1 14 - 20 2015年01月 [査読有り][通常論文]
   

  The purposes of this study are to develop and validate new diagnostic criteria for acute retinal necrosis (ARN) based on the ocular findings, clinical course, and virologic testing of intraocular fluids. The Japanese ARN Study Group, comprising 8 uveitis specialists and 1 statistician, was formed to develop new diagnostic criteria for ARN. The criteria used a combination of clinical features consistent with ARN including 6 early-stage ocular findings ([1a] anterior chamber cells or mutton-fat keratic precipitates; [1b] yellow-white lesion(s) in the peripheral retina [granular or patchy in the early stage, then gradually merging]; [1c] retinal arteritis; [1d] hyperemia of the optic disc; [1e] inflammatory vitreous opacities; and [1f] elevated intraocular pressure), 5 clinical courses ([2a] rapid expansion of the retinal lesion(s) circumferentially, [2b] development of retinal breaks or retinal detachment, [2c] retinal vascular occlusion, [2d] optic atrophy, and [2e] response to antiviral agents), and the results of virologic testing of intraocular fluids by means of either polymerase chain reaction or the Goldmann-Witmer coefficient for herpes simplex virus or varicella zoster virus. Various combinations of findings were analyzed to maximize the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The criteria were then used to retrospectively analyze patients who had been diagnosed as having ARN or control uveitis. Patients were followed at 1 of 7 tertiary uveitis clinics between 2009 and 2011. Analysis of the data allowed delineation of 2 levels of diagnosis: "virus-confirmed ARN" (defined as the presence of both early-stage ocular findings 1a and 1b, the presence of any 1 of the 5 clinical courses, and a positive virologic test result) and "virus-unconfirmed ARN" (defined as the presence of 4 of 6 early-stage ocular findings including 1a and 1b, presence of any 2 of the 5 clinical courses, and a negative virologic test result, or when virologic testing had not been performed). The new diagnostic criteria were applied to 45 patients with ARN and 409 patients with control uveitis, resulting in a sensitivity of 0.89, a specificity of 1.00, a PPV of 1.00, and an NPV of 0.99. New diagnostic criteria for ARN were developed and found to achieve high statistical values.
• Amelioration of experimental autoimmune uveoretinitis by inhibition of glyceraldehyde-derived advanced glycation end-product formation

  Zhenyu Dong, Daiju Iwata, Nobuyoshi Kitaichi, Masayoshi Takeuchi, Masashi Sato, Noriko Endo, Kazuya Iwabuchi, Ryo Ando, Junichi Fukuhara, Satoshi Kinoshita, Anton Lennikov, Mizuki Kitamura, Kazuomi Mizuuchi, Atsuhiro Kanda, Kousuke Noda, Kenichi Namba, Sho-Ichi Yamagishi, Shigeaki Ohno, Susumu Ishida

  JOURNAL OF LEUKOCYTE BIOLOGY 96 6 1077 - 1085 2014年12月 [査読有り][通常論文]
   

  Formation of glyceraldehyde-derived advanced glycation endoproducts contributes to the pathogenesis of endogenous uvetitis in human and animals. AGEs are permanently modified macromolecule derivatives that form through nonenzymatic glycation of amino groups of proteins. Glycer-AGEs are highly toxic and play an important role in the pathogenesis of chronic inflammatory diseases. However, the contribution of glycer-AGEs to the pathogenesis of uveitis is unclear. In this study, we measured serum levels of glycer-AGEs in 100 patients with endogenous uveitis (22 with HLA-B27-associated uveitis, 20 with VKH disease, 14 with Behcet's disease, and 44 with sarcoidosis) and 33 healthy volunteers. We then examined the effect of the AGE inhibitor in a mouse model of human endogenous uveitis (EAU) by continuous oral administration of pyridoxamine at 200 or 400 mg/kg/day. Regardless of the etiology, serum glycer-AGE levels were significantly higher in patients with uveitis than in healthy subjects. Treatment with 400 mg/kg pyridoxamine significantly reduced the clinical and histological severity of EAU and was accompanied by a significant decrease in serum and retinal glycer-AGE levels and suppression of translocation of NF-B p65 into the nucleus of retinal cells. Serum glycer-AGE levels may therefore serve as a biomarker of human uveitis, as well as systemic inflammation, and may contribute to the progression of uveitis, including diabetic iritis, via the activation of NF-B.
• Evaluation of the long-term efficacy and safety of infliximab treatment for uveitis in Behçet's disease: a multicenter study.

  Takeuchi M, Kezuka T, Sugita S, Keino H, Namba K, Kaburaki T, Maruyama K, Nakai K, Hijioka K, Shibuya E, Komae K, Hori J, Ohguro N, Sonoda KH, Mizuki N, Okada AA, Ishibashi T, Goto H, Mochizuki M

  Ophthalmology 121 10 1877 - 1884 2014年10月 [査読有り][通常論文]
   

  Purpose: To evaluate the long-term efficacy and safety of infliximab for the treatment of uveitis in Behcet's disease (BD). Design: Retrospective multicenter study using a questionnaire. Participants: A total of 164 consecutive patients with BD treated with infliximab for more than 1 year were studied. The mean age at initiation of infliximab treatment was 42.6 +/- 11.7 years, and the mean treatment duration was 32.9 +/- 14.4 months. Methods: Data before and at the last visit during infliximab treatment were analyzed in 4 groups divided by duration of treatment: group A (n = 43, 12-<24 months), group B (n = 62, 24-<36 months), group C (n = 42, 36-<48 months), and group D (n = 17, >= 48 months). Main Outcome Measures: Best-corrected visual acuity (BCVA), relapse of ocular inflammation, numbers of ocular inflammatory attacks per year, and adverse effects of infliximab therapy. Results: The frequency of ocular attacks decreased in all groups (from 5.3 +/- 3.0 to 1.0 +/- 0.3 in group A, 4.8 +/- 4.6 to 1.4 +/- 0.3 in group B, 4.1 +/- 2.9 to 0.9 +/- 0.3 in group C, and 9.5 +/- 5.8 to 1.6 +/- 0.5 in group D; all P < 0.05). The BCVA was improved in approximately 55% of the eyes after treatment. Mean BCVA converted to logarithm of the minimum angle of resolution was improved after treatment with infliximab in groups A to C (from 0.79 +/- 1.04 to 0.59 +/- 0.94 in group A, 0.59 +/- 1.07 to 0.41 +/- 1.04 in group B, and 1.15 +/- 1.77 to 0.92 +/- 1.73 in group C; all P < 0.05) but not in group D. Uveitis relapsed in 59.1% of all patients after infliximab treatment, and no difference in duration until relapse was observed between individual groups. Approximately 80% of relapses occurred within 1 year after the initiation of infliximab treatment in all groups, 90% of which were controlled by increasing doses of topical corticosteroids and shortening the interval of infliximab infusion. Adverse effects were observed in 65 cases or 35% of all subjects. Infliximab treatment was continued in 85% of the patients, but 15% of the patients discontinued infliximab treatment because of adverse effects or insufficient efficacy. Conclusions: Infliximab reduced the frequency of ocular attacks and improved visual acuity in patients with BD-related uveitis and was generally well tolerated with few serious adverse events. (C) 2014 by the American Academy of Ophthalmology.
• Therapeutic effects of 0.1% tacrolimus eye drops for refractory allergic ocular diseases with proliferative lesion or corneal involvement

  Atsuki Fukushima, Yuichi Ohashi, Nobuyuki Ebihara, Eiichi Uchio, Shigeki Okamoto, Naoki Kumagai, Jun Shoji, Etsuko Takamura, Yayoi Nakagawa, Kenichi Namba, Hiroshi Fujishima, Dai Miyazaki

  BRITISH JOURNAL OF OPHTHALMOLOGY 98 8 1023 - 1027 2014年08月 [査読有り][通常論文]
   

  Background The objective of this study was to investigate the efficacy of topical 0.1% tacrolimus in treating refractory allergic conjunctivitis with proliferative lesions and/or corneal involvement. Methods This prospective observational study included 1436 patients with refractory allergic conjunctivitis whose condition had responded poorly to conventional antiallergic drugs and/or topical steroids and/or topical cyclosporine. All patients received tacrolimus eye drops twice daily during the study period. Ten clinical signs and six clinical symptoms were rated on a four-grade scale. The primary endpoint was the change from baseline in total clinical signs and symptoms score at the last observation or following 6 months of treatment. Results Total signs and symptoms score significantly decreased after 1 month of treatment (p<0.001). Giant papillae and corneal lesions were also reduced by tacrolimus eye drop use (p<0.001). The drug proved effective in patients whose condition did not respond well to topical cyclosporine therapy. About 50% of all patients using topical steroids were weaned. The most common adverse reaction was a transient burning sensation (3.20%). Conclusions Tacrolimus eye drops are highly effective in treating refractory allergic conjunctivitis with proliferative lesions and/or corneal involvement, and may reduce or replace topical steroid use.
• [A case report of malignant lymphoma receiving infliximab therapy with Behçet's disease].

  Sonoda KH, Fukuhara T, Yoshikawa H, Takeda A, Yoshimura T, Akahoshi M, Kusumoto H, Kohno K, Kato K, Akashi K, Kohashi K, Aijima S, Namba K, Ishibashi T

  Nippon Ganka Gakkai zasshi 118 5 440 - 445 2014年05月 [査読有り][通常論文]
  
• Behçet's disease ocular attack score 24: evaluation of ocular disease activity before and after initiation of infliximab.

  Kaburaki T, Namba K, Sonoda KH, Kezuka T, Keino H, Fukuhara T, Kamoi K, Nakai K, Mizuki N, Ohguro N, Ocular Behçet, Disease Research, Group of Japan

  Japanese journal of ophthalmology 58 2 120 - 130 2014年03月 [査読有り][通常論文]
   

  We developed a novel scoring system for uveitis due to Beh double dagger et's disease (BD), termed Beh double dagger et's disease ocular attack score 24 (BOS24), and examined its validity and usefulness by estimating changes in ocular disease activities both before and after initiation of infliximab therapy. BOS24 consists of a total 24 points divided into 6 parameters of ocular inflammatory symptoms. To examine the validity of our scoring system, 5 uveitis specialists examined the severity of 50 ocular attacks in clinical charts using both our system and a physician's impression score (grade 1-10). In addition, ocular disease activities both before and after initiation of infliximab were retrospectively examined in 150 cases of ocular BD using BOS24. The average BOS24 for the 5 doctors was highly correlated with the average physician's impression score (p < 0.0001), whereas the coefficient of variance for BOS24 among doctors was much lower than that for the physician's impression score (p < 0.0001). Summation of BOS24 over a 6-month period (BOS24-6M) was significantly reduced after starting infliximab therapy (p < 0.0001). The average BOS24 for individual ocular attacks was also significantly decreased after starting infliximab, with scores for the posterior pole and fovea notably improved. BOS24 was highly related to severity noted by the physician's impression and had a low level of variability among the examined doctors. Using our novel scoring system, infliximab therapy was shown to reduce not only the frequency of ocular attacks, but also the severity of each attack. BOS24 is a promising tool for evaluating ocular BD activities.
• Amelioration of endotoxin-induced uveitis treated with the sea urchin pigment echinochrome in rats

  Anton Lennikov, Nobuyoshi Kitaichi, Kousuke Noda, Kazuomi Mizuuchi, Ryo Ando, Zhenyu Dong, Junichi Fukuhara, Satoshi Kinoshita, Kenichi Namba, Shigeaki Ohno, Susumu Ishida

  MOLECULAR VISION 20 171 - 177 2014年02月 [査読有り][通常論文]
   

  Purpose: Echinochrome is a pigment present in the shells and spines of sea urchins. It has been reported to have several biologic protective effects, including in experimental models of myocardial ischemia/reperfusion injury, for which the proposed mechanisms are scavenging reactive oxygen species (ROS) and chelating iron. Endotoxin-induced uveitis (EIU) is an animal model of acute anterior segment intraocular inflammation that is induced by the injection of lipopolysaccharide (LPS). In this study, the therapeutic effect of echinochrome was examined in uveitis using the EIU model. Methods: EIU was induced in Lewis rats via 200 mu g subcutaneous injections of LPS from Escherichia coli. Echinochrome was administered intravenously in 10, 1, or 0.1 mg/kg doses suspended in PBS (controls were injected with PBS only). Twenty-four hours after LPS injection, the number of infiltrating cells and the protein concentration in aqueous humor were determined. Aqueous tumor necrosis factor alpha (TNF-alpha) concentration was quantified with enzyme-linked immunosorbent assay, eyes were stained with nuclear factor (NF) kappa B antibodies, and ROS production was determined by dihydroethidium staining in fresh frozen samples. Results: The number of inflammatory aqueous cells and protein levels were lower in the groups treated with 10 and 1 mg/kg of echinochrome than in the untreated LPS group (p<0.01). Treatment with 10 and 1 mg/kg of echinochrome significantly reduced TNF-alpha concentrations in aqueous humor (p<0.01). The numbers of NF kappa B-positive cells and ROS signals were also reduced by echinochrome administration (p<0.05). Conclusions: Echinochrome ameliorated intraocular inflammation caused by EIU by reducing ROS production, thereby also decreasing the expression of NF kappa B and TNF-alpha. As a natural pigment, echinochrome may therefore be a promising candidate for the safe treatment of intraocular inflammation. The use of sea urchin shells and spines in health foods and medical products is thus both economically and environmentally meaningful.
• Genome-wide association study identifies GIMAP as a novel susceptibility locus for Behcet's disease

  Yun Jong Lee, Yukihiro Horie, Graham R. Wallace, Yong Seok Choi, Ji Ah Park, Ji Yong Choi, Ran Song, Young-Mo Kang, Seong Wook Kang, Han Joo Baek, Nobuyoshi Kitaichi, Akira Meguro, Nobuhisa Mizuki, Kenichi Namba, Susumu Ishida, Jinhyun Kim, Edyta Niemczyk, Eun Young Lee, Yeong Wook Song, Shigeaki Ohno, Eun Bong Lee

  ANNALS OF THE RHEUMATIC DISEASES 72 9 1510 - 1516 2013年09月 [査読有り][通常論文]
   

  Objectives To identify non-major histocompatibility complex susceptible genes that might contribute to Behcet's disease (BD). Methods We performed a genome-wide association study using DNA samples from a Korean population consisting of 379 BD patients and 800 controls. A replication study was performed in a Japanese population (363 BD patients and 272 controls). To evaluate the functional implication of the target single nucleotide polymorphisms (SNP), gene expression levels in peripheral T cells, allele-specific modulation of promoter activity and biological effect of mRNA knockdown were investigated. Results We found a novel association of BD to the GIMAP locus, mapped to chromosome 7q36.1 (rs1608157, p=6.01x10(-8) in a minor allele dominant model; rs11769828, allele based p=1.60x10(-6)). A fine mapping study identified an association with four additional SNP: rs1522596 (OR=1.45, p=7.70x10(-6)) in GIMAP4; rs10266069 (OR=1.32, p=2.67x10(-4)) and rs10256482 (OR=1.27, p=5.27x10(-4)) in GIMAP2; and rs2286900 (OR=1.61, p=3.53x10(-5)) in GIMAP1 areas. Replication study using DNA samples from the Japanese population validated the significant association between BD and the GIMAP locus. The GIMAP4 promoter construct plasmid with the minor allele of rs1608157 displayed significantly lower activity than one with the major allele. Moreover, CD4 T cells from BD patients showed a lower level of GIMAP4 mRNA, and GIMAP4 knockdown was protective against Fas-mediated apoptosis. Conclusions These results suggest that a GIMAP cluster is a novel susceptibility locus for BD, which is involved in T-cell survival, and T-cell aberration can contribute to the development of BD.
• Clinical features of human T lymphotropic virus type 1-associated uveitis in Hokkaido, Japan

  Satoru Kase, Kenichi Namba, Nobuyoshi Kitaichi, Daiju Iwata, Shigeaki Ohno, Susumu Ishida

  JAPANESE JOURNAL OF OPHTHALMOLOGY 57 4 379 - 384 2013年07月 [査読有り][通常論文]
   

  To clarify the clinical features of human lymphotropic virus type 1 (HTLV-1)-associated uveitis (HAU) in patients of Hokkaido University Hospital, Hokkaido, northern Japan. We reviewed the records of a consecutive series of 21 patients with HAU who were followed up for more than 12 months at Hokkaido University Hospital. Of the 21 patients enrolled in this study, 19 as well as their parents (90.5 %) were born in Hokkaido. One patient was a member of the Ainu ethnic group. Unilateral involvement was found in 16 cases (76 %). In the ophthalmological examinations, vitreous opacity was most frequently followed by keratic precipitate, iris/gonio nodules, and posterior synechiae, while hypopyon, retinal vasculitis, and neovascularization were rarely observed. Intraocular inflammation was controlled by topical treatment, while systemic corticosteroids were required in less than one-fourth of patients. Visual acuity improved in 15 patients, remained unchanged in four patients, and deteriorated in two patients. HAU was observed in two patients with adult T-cell leukemia/lymphoma (ATLL). Three out of the four patients (75 %) for whom HLA typing was available had HLA-A26. A number of clinical features were unique to Hokkaido, namely, predominant unilateral involvement, as well as two HAU patients with ATLL. The phylogenetic difference of HTLV-1 and HLA typing may correlate with different clinical manifestations in HAU.
• Trabecular meshwork depigmentation in Vogt-Koyanagi-Harada disease.

  Kazuomi Mizuuchi, Nobuyoshi Kitaichi, Kenichi Namba, Yukihiro Horie, Susumu Ishida, Shigeaki Ohno

  Japanese journal of ophthalmology 57 3 245 - 51 2013年05月 [査読有り][通常論文]
   

  PURPOSE: Since some patients develop depigmentation of the trabecular meshwork in the course of Vogt-Koyanagi-Harada (VKH) disease, we examined the incidence of trabecular depigmentation and its correlation with other ocular findings and systemic symptoms. METHODS: We retrospectively reviewed the clinical charts of 53 Japanese patients diagnosed with VKH disease. The scores of trabecular and limbal pigmentation of all patients were recorded. We then examined the correlation between trabecular pigmentation and the presence of sunset glow fundus or skin lesions. RESULTS: Trabecular pigmentation was significantly lower in the patients with sunset glow fundus than in those without it (P = 0.022), whereas limbal pigmentation showed no significance. However, there were no significant differences in trabecular and limbal pigmentation between the patients with and those without skin lesions. Furthermore, there was no correlation between trabecular and limbal pigmentation. CONCLUSIONS: Depigmentation of the trabecular meshwork develops in some patients in the course of VKH disease. This depigmentation is significantly correlated with sunset glow fundus, but not with limbal depigmentation or skin lesions.
• Acute retinal necrosis: factors associated with anatomic and visual outcomes

  Chiharu Iwahashi-Shima, Atsushi Azumi, Nobuyuki Ohguro, Annabelle A. Okada, Toshikatsu Kaburaki, Hiroshi Goto, Koh-Hei Sonoda, Kenichi Namba, Nobuhisa Mizuki, Manabu Mochizuki

  JAPANESE JOURNAL OF OPHTHALMOLOGY 57 1 98 - 103 2013年01月 [査読有り][通常論文]
   

  To examine the factors associated with anatomic and visual outcomes in Japanese patients with acute retinal necrosis (ARN). One hundred four patients with ARN who were followed for more than 1 year at nine referral centers were reviewed. Retinal involvement at initial presentation was classified into four groups: zone 1 (posterior pole, n = 22), zone 2 (midperiphery, n = 54), zone 3 (periphery, n = 25), and unknown (n = 3). Forty-eight eyes underwent prophylactic vitrectomy before development of retinal detachment (vitrectomy group); 56 eyes were treated conventionally without prophylactic vitrectomy (observation group). The retina was attached in 28 of 48 eyes (58.3 %) in the vitrectomy group and 42 of 56 eyes (75.0 %) in the observation group at the final visit (P = 0.071). At 1 year, 56 eyes (53.8 %) had a best-corrected visual acuity (BCVA) of 20/200 or worse. Multivariate logistic regression analyses identified zone 1 disease (odds ratio = 4.983) and optic nerve involvement (odds ratio = 5.084) as significantly associated with BCVA of 20/200 or worse. Among the zone 3 eyes, significantly (P = 0.012) more eyes in the observation group than in the vitrectomy group had an attached retina. Prophylactic vitrectomy did not improve the final BCVA in any eyes. Zone 3 eyes had better outcomes without prophylactic vitrectomy.
• Two cases of subfoveal choroidal neovascularization with tubulointerstitial nephritis and uveitis syndrome

  Yuko Takemoto, Kenichi Namba, Kazuomi Mizuuchi, Shigeaki Ohno, Susumu Ishida

  European Journal of Ophthalmology 23 2 255 - 257 2013年 [査読有り][通常論文]
   

  Purpose. Tubulointerstitial nephritis and uveitis (TINU) syndrome usually shows anterior segment intraocular inflammation, but severe posterior segment intraocular inflammation is rarely observed. We report 2 children with TINU syndrome complicated by subfoveal choroidal neovascularization (CNV). Methods. Case reports. Results. Patients were a 12-year-old girl and a 12-year-old boy diagnosed with probable TINU syndrome on the basis of typical ocular findings and high value of urinary β2 microglobulin even though renal biopsy was not performed. The girl showed development of CNV with subretinal macular hemorrhage along with the exacerbation of anterior chamber inflammation in her left eye. Subretinal macular hemorrhage recurred frequently even with oral prednisolone therefore, intravitreal injection of bevacizumab (IVB) was performed. After IVB, the subretinal proliferative tissue shrunk and subretinal hemorrhage has not recurred for 5 years. The boy showed subretinal hemorrhage from CNV with severe anterior chamber inflammation in his left eye. With oral prednisolone, anterior chamber inflammation and subretinal hemorrhage disappeared, but shrunken subretinal fibrosis in the macula remained. Final visual acuity was poor due to residual subretinal fibrosis in both cases. Conclusions. Tubulointerstitial nephritis and uveitis syndrome has a potential to develop CNV that leads to severe visual loss therefore, prompt anti-inflammatory therapy is required, and IVB should be regarded as a potential choice of treatment. © 2013 Wichtig Editore.
• Bacterial endophthalmitis caused by an intraocular cilium in a patient under treatment with infliximab

  Xue-Hai Jin, Kenichi Namba, Wataru Saito, Daiju Iwata, Susumu Ishida

  Journal of Ophthalmic Inflammation and Infection 3 1 1 - 3 2013年 [査読有り][通常論文]
   

  Background: We report a case of bacterial endophthalmitis caused by an intraocular cilium in a patient without any history of trauma or ocular surgery. Findings: A 32-year-old Caucasian male showed symptoms of orbital myositis and scleritis, with no intraocular inflammation in the right eye. The patient had been treated with infliximab for Crohn's disease. Three weeks after initiation of oral prednisolone therapy, he developed bacterial endophthalmitis. During pars plana vitrectomy, a cilium in the massive vitreous opacity was found. A focal scleral necrosis was detected just outside where the cilium was intraoperatively observed. Vitreous culture showed the presence of Staphylococcus aureus. Conclusions: The intraocular cilium seemed to be the aetiology of the endophthalmitis in this case, which suggests that anti-tumour necrosis factor-α therapy may play a role in the migration of cilia into the globe and the occurrence of endophthalmitis. © 2013 Jin et al.
• Genetic Characterization and Susceptibility for Sarcoidosis in Japanese Patients: Risk Factors of BTNL2 Gene Polymorphisms and HLA Class II Alleles

  Hitomi Suzuki, Masao Ota, Akira Meguro, Yoshihiko Katsuyama, Tatukata Kawagoe, Mami Ishihara, Yuri Asukata, Masaki Takeuchi, Norihiko Ito, Etsuko Shibuya, Eiichi Nomura, Riyo Uemoto, Tadayuki Nishide, Kenichi Namba, Nobuyoshi Kitaichi, Shin-ichiro Morimoto, Toshikatsu Kaburaki, Yasutaka Ando, Shinobu Takenaka, Jutaro Nakamura, Kozou Saeki, Shigeaki Ohno, Hidetoshi Inoko, Nobuhisa Mizuki

  INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 53 11 7109 - 7115 2012年10月 [査読有り][通常論文]
   

  PURPOSE. Sarcoidosis is a heterogeneous and multisystem granulomatous disorder. The etiology still is uncertain, but the disease currently is thought to be triggered by various genetic as well as environmental factors. Recently, an association between sarcoidosis and the butyrophilin-like 2 (BTNL2) gene located in close proximity to the HLA-DRB1 gene was reported. The purpose of our study was to verify the relationship between BTNL2 and HLA risk alleles for the susceptibility to sarcoidosis, and to assess whether the BTNL2 association is independent of the HLA risk alleles. METHODS. In our study, 11 single nucleotide polymorphisms (rs28362677, rs2076533, rs2076530, rs2076529, rs2294881, rs3763304, rs2076523, rs28362682, rs3806156, rs9268499, rs3763317), including the functional rs2076530 (G > A) of the BTNL2 gene, and HLA-DRB1 and -DQB1 alleles, were genotyped in 237 Japanese patients diagnosed with sarcoidosis and 287 healthy Japanese control subjects. RESULTS. In the patient group, the HLA-DRB1*08:03 (P = 6.15 X 10(-5), odds ratio [OR] = 2.43) and BTNL2 rs2076530_A (P = 6.90 X 10(-6), OR = 1.84) were associated with disease susceptibility. Upon stratification analysis in search for a synergistic effect given the extensive linkage disequilibrium between BTNL2 rs2076530_A and HLA-DRB1*08:03, our results suggested that the risk-bearing allele of these two loci interact negatively. No significant differences were observed in allele frequencies for alleles in patients with ocular and other systemic sarcoidosis. CONCLUSIONS. Our studies implicated that the HLA-DRB1 allele is a major contributing genetic factor in the development of sarcoidosis in Japan. However, further studies are needed to verify how HLA or BTNL2 alleles confer the disease phenotype, severity of sarcoidosis. (Invest Ophthalmol Vis Sci. 2012;53:7109-7115) DOI:10.1167/iovs.12-10491
• Amelioration of endotoxin-induced uveitis treated with an IκB kinase β inhibitor in rats.

  Lennikov A, Kitaichi N, Noda K, Ando R, Dong Z, Fukuhara J, Kinoshita S, Namba K, Mizutani M, Fujikawa T, Itai A, Ohno S, Ishida S

  Molecular vision 18 267-70 2586 - 2597 2012年10月 [査読有り][通常論文]
   

  Purpose: Endotoxin-induced uveitis (EIU) is an animal model for acute ocular inflammation. Several substances play major roles in the development of inflammatory changes in EIU, including tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, and IL-6. These inflammatory cytokines trigger the degradation of I kappa B by activating I kappa B kinases (IKKs). Released nuclear factor kappaB (NF kappa B) subsequently translocates to the nucleus, where NF kappa B expresses its proinflammatory function. IMD-0354, N-(3,5-Bis-trifluoromethylphenyl)-5-chloro-2-hydroxybenzamide, selectively inhibits IKK beta, particularly when induced by proinflammatory cytokines, such as TNF-alpha and IL-1 beta. In the present study, we examined whether IKK beta inhibition has therapeutic effects on EIU by using IMD-0354 and its prodrug IMD-1041. Methods: Six-week-old male Lewis rats were used. EIU was induced with subcutaneous injections of 200 mu g of lipopolysaccharide (LPS) from Escherichia coli that had been diluted in 0.1 ml of phosphate-buffered saline. IMD-0354 was administered intraperitoneally at 30, 10, 3, or 0 mg/kg, suspended in 1.0 ml of 0.5% carboxymethyl cellulose sodium. The prodrug IMD-1041 (100 mg/kg) was also administered orally. The rats were euthanized 24 h after LPS injection, and EIU severity was evaluated histologically. The number of infiltrating cells and the protein, TNF-alpha, and monocyte chemoattractant protein-1 (MCP-1) concentrations in the aqueous humor were determined. TNF-alpha and MCP-1 concentrations were quantified with enzyme-linked immunosorbent assay. Eye sections were also stained with anti-NF kappa B and phosphorylated I-kappa B alpha antibodies. Results: The number of infiltrating cells in aqueous humor was 53.6 +/- 9.8x10(5), 72.5 +/- 17.0x10(5), 127.25 +/- 32.0x10(5), and 132.0 +/- 25.0x10(5) cells/ml in rats treated with 30, 10, 3, or 0 mg/kg of IMD-0354, respectively. The total protein concentrations of aqueous humor were 92.6 +/- 3.1 mg/ml, 101.5 +/- 6.8 mg/ml, 112.6 +/- 1.9 mg/ml, and 117.33 +/- 1.8 mg/ml in rats treated with 30, 10, 3, and 0 mg/kg of IMD-0354, respectively. Infiltrating cells and protein concentrations were significantly decreased by treatment with IMD-0354 (p < 0.01). IMD-0354 treatment significantly reduced the concentration of TNF-alpha (p < 0.05) and MCP-1 (p < 0.01) in aqueous humor. The number of NF kappa B positive nuclei was reduced when treated with IMD-0354. Furthermore, IMD-0354-treated EIU rats showed only background levels of phosphorylated I-kappa B alpha; however, it was strongly expressed in the iris-ciliary body cell cytoplasm of the IMD-0354 untreated EIU rats. Oral administration of IMD-1041 also decreased the cell number (p < 0.01) and protein concentration (p < 0.05) of aqueous humor in EIU. Conclusions: Acute uveitis was ameliorated by inhibition of IKK beta in rats. IMD-0354 and its prodrug IMD-1041 seem to be promising candidates for treating intraocular inflammation/uveitis.
• Correlation between elevation of serum antinuclear antibody titer and decreased therapeutic efficacy in the treatment of Behçet's disease with infliximab.

  Iwata D, Namba K, Mizuuchi K, Kitaichi N, Kase S, Takemoto Y, Ohno S, Ishida S

  Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 250 7 1081 - 1087 7 2012年07月 [査読有り][通常論文]
   

  Infliximab, an anti-TNF-alpha monoclonal antibody, administered to Beh double dagger et's disease (BD) patients in Japan with refractory intraocular inflammation, has shown excellent clinical results. However, some patients demonstrate a decreased response to infliximab during the course of the treatment. In the present study, we investigated the correlation between this reduced therapeutic effect and elevation of the serum antinuclear antibody (ANA) titers in patients with BD who were undergoing infliximab therapy. Seventeen patients (14 males and three females) with uveitis in BD who were undergoing treatment with infliximab for 2 years or longer were enrolled. Their blood test results and clinical histories were obtained from medical records. One patient (5.9%) was ANA-positive prior to the initiation of infliximab, and 11 patients (64.7%) developed positive ANA during the therapy. The appearance of ANA was observed 6 months after the initiation of the infliximab therapy, and its titers gradually increased. None of the patients showed lupus symptoms. Five patients (29.4%) have suffered from ocular inflammatory attacks since the sixth month from the initiation of infliximab treatment and all of them were ANA-positive. In contrast, four patients (23.5%) who were ANA-negative experienced no ocular attacks during the follow-up period. Here we report the positive conversion and subsequent elevation of serum ANA titers in some patients with BD after the initiation of infliximab therapy. Since all recurrences of uveitis were shown only in the ANA-positive patients, serum ANA titer may be a helpful biomarker for predicting the recurrence of ocular attacks in BD patients treated with anti-TNF-alpha antibody therapies.
• Replication of a microsatellite genome-wide association study of Behcet's disease in a Korean population

  Yukihiro Horie, Akira Meguro, Nobuyoshi Kitaichi, Eun Bong Lee, Atsuhiro Kanda, Kousuke Noda, Yeong Wook Song, Kyung Sook Park, Kenichi Namba, Masao Ota, Hidetoshi Inoko, Nobuhisa Mizuki, Susumu Ishida, Shigeaki Ohno

  RHEUMATOLOGY 51 6 983 - 986 2012年06月 [査読有り][通常論文]
   

  Objective. Behcet's disease is one of the major aetiologies of uveitis causing blindness in Asian countries. A genome-wide association study identified six microsatellite markers as disease susceptibility loci for Japanese patients with Behcet's disease. To confirm our recent results, these microsatellite markers were examined in a Korean population as a replication study. Methods. Study participants included 119 Behcet's disease patients and 141 controls. All were enrolled in Korea. Association between the six reported microsatellite markers (D3S0186i, D6S0014i, D6S0032i, 536G12A, D12S0645i and D22S0104i) and Behcet's disease was analysed. HLA-B was genotyped by sequence-based typing methods. Results. A microsatellite marker located near the HLA-B region demonstrated significant association with Behcet's disease (P = 0.028). The genotype and phenotype frequencies of the HLA-B*51 gene were significantly increased in patients (23.1 and 39.5%, respectively) compared with healthy controls (11.2 and 20.1%, respectively; P < 0.001). Conclusion. Microsatellite analysis revealed that the HLA-B*51 gene was strongly associated with Behcet's disease in a Korean population.
• Blood Level of Tacrolimus in Patients with Severe Allergic Conjunctivitis Treated by 0.1% Tacrolimus Ophthalmic Suspension

  Nobuyuki Ebihara, Yuichi Ohashi, Hiroshi Fujishima, Atsuki Fukushima, Yayoi Nakagawa, Kenichi Namba, Shigeki Okamoto, Jun Shoji, Etsuko Takamura, Eiichi Uchio, Dai Miyazaki

  ALLERGOLOGY INTERNATIONAL 61 2 275 - 282 2012年06月 [査読有り][通常論文]
   

  Background: To estimate the efficacy and safety of 0.1% tacrolimus ophthalmic suspension based on the blood level of tacrolimus in patients with severe allergic conjunctivitis. Methods: Fifty-two patients in whom topical anti-allergic agents had been ineffective were treated with 0.1% tacrolimus ophthalmic suspension twice daily for 12 weeks. Adverse drug reactions were monitored, as well as ocular symptoms and signs. The blood concentration of tacrolimus was measured before the initiation of treatment and 4 and 12 weeks later. Results: About 75% of the patients without concomitant using of tacrolimus ointment had blood levels of tacrolimus below the detection limit of the assay (0.5 ng/mL). On the other hand, 71% (week 4) and 57% (week 12) of patients with concomitant using of tacrolimus ointment had blood levels above the detection limit of the assay. However, the maximum blood concentration was less than 2 ng/mL. Adverse drug reactions occurred in 16 patients. These were disorders of the eye such as warmness, irritation, and a burning sensation. However, all of the patients could continue treatment with tacrolimus for 12 weeks. There were no serious adverse events such as increased intraocular pressure or ocular infection during the study. All symptoms and signs improved over time. Conclusions: The good safety profile of 0.1% tacrolimus ophthalmic suspension based on the low blood concentration of tacrolimus, coupled with demonstrated efficacy, make it an important tool for treating severe allergic conjunctivitis.
• Spontaneous Regression of Intraocular Lymphoma

  Satoru Kase, Kenichi Namba, Xue-Hai Jin, Kanako C. Kubota, Susumu Ishida

  OPHTHALMOLOGY 119 5 1083 - 1084 2012年05月 [査読有り][通常論文]
  
• Chickenpox chorioretinitis with retinal exudates and periphlebitis.

  Hirokuni Kitamei, Kenichi Namba, Nobuyoshi Kitaichi, Akiko Wakayama, Shigeaki Ohno, Susumu Ishida

  Case reports in ophthalmology 3 2 180 - 4 2012年05月 [査読有り][通常論文]
   

  BACKGROUND: Chickenpox is rarely associated with posterior segment inflammation. We report on a case of unilateral chickenpox chorioretinitis with retinal exudates and periphlebitis. CASE PRESENTATION: A 21-year-old healthy man, who suffered from chickenpox 2 weeks prior to symptom development, exhibited mild anterior chamber cells, vitreous opacity, sheathing of retinal veins, and yellow-white exudates in his right eye. Varicella zoster virus DNA was detected by polymerase chain reaction in the aqueous humor. He was treated with intravenous acyclovir followed by oral prednisolone and valaciclovir. Aqueous cells quickly disappeared and retinal exudates diminished within 1 month, leaving faint retinal scarring. Retinal arteritis had never been observed in this patient. CONCLUSIONS: ALTHOUGH THE OCULAR FINDINGS IN THIS CASE WERE SIMILAR TO ACUTE RETINAL NECROSIS (ARN), THE CLINICAL FEATURES DIFFERED FROM ARN IN THE FOLLOWING POINTS: (1) mild anterior chamber inflammation, (2) absence of retinal arteritis, and (3) prompt resolution of inflammatory findings. The distinctive clinical features indicated that chorioretinitis associated with chickenpox may not have the same pathological conditions as ARN.
• Lack of association between IL10 polymorphisms and sarcoidosis in Japanese patients

  Kenichi Sakuyama, Akira Meguro, Masao Ota, Mami Ishihara, Riyo Uemoto, Haruyasu Ito, Eiichi Okada, Kenichi Namba, Nobuyoshi Kitaichi, Shin-ichiro Morimoto, Toshikatsu Kaburaki, Yasutaka Ando, Shinobu Takenaka, Takenosuke Yuasa, Shigeaki Ohno, Hidetoshi Inoko, Nobuhisa Mizuki

  MOLECULAR VISION 18 56 512 - 518 2012年02月 [査読有り][通常論文]
   

  Purpose: To investigate whether interleukin 10 (IL10) gene polymorphisms are associated with the development of sarcoidosis in Japanese patients. Methods: Two hundred and eighty-eight Japanese sarcoidosis patients and 310 Japanese healthy controls were recruited. We genotyped 9 single-nucleotide polymorphisms in IL10 and assessed the allelic diversity between cases and controls. Results: No significant differences in the frequency of IL10 alleles, genotypes, and haplotypes in the sarcoidosis cases compared to the controls were detected. Conclusions: Our results suggest that IL10 polymorphisms are not significantly related to the pathogenesis of sarcoidosis in the Japanese population.
• Intravitreal injection of bevacizumab in a case of occlusive retinal vasculitis accompanied by syphilitic intraocular inflammation

  Kan Ishijima, Kenichi Namba, Shigeaki Ohno, Kiyofumi Mochizuki, Susumu Ishida

  Case Reports in Ophthalmology 3 3 434 - 437 2012年 [査読有り][通常論文]
   

  Background: We report a rare case of syphilitic intraocular inflammation with occlusive retinal vasculitis treated with intravitreal injection of bevacizumab (IVB) in addition to conventional therapy for syphilis. Case: A 24-year-old woman who complained floaters in both her eyes showed occlusive retinal vasculitis OU. According to the high titer of the Treponema antigen and characteristic cutaneous eruption, she was diagnosed as secondary syphilis. Observation: She was treated with oral amoxicillin and retinal photocoagulation OU. Then, administration of prednisolone was required to the intraocular inflammations considered as Jarisch-Herxheimer reactions. IVB was also performed toward exacerbated retinal neovascularization and showed transient effects. Conclusion: We experienced a rare case of occlusive retinal vasculitis accompanied by syphilis intraocular inflammation. IVB was considered to be effective as an adjunctive therapy for inflammatory neovascularizations. © 2012 S. Karger AG, Basel.
• Investigation of Association between TLR9 Gene Polymorphisms and VKH in Japanese Patients

  Ryuta Ito, Masao Ota, Akira Meguro, Yoshihiko Katsuyama, Riyo Uemoto, Eiichi Nomura, Tadayuki Nishide, Nobuyoshi Kitaichi, Yukihiro Horie, Kenichi Namba, Shigeaki Ohno, Hidetoshi Inoko, Nobuhisa Mizuki

  OCULAR IMMUNOLOGY AND INFLAMMATION 19 3 202 - 205 2011年06月 [査読有り][通常論文]
   

  Purpose: Vogt-Koyanagi-Harada (VKH) disease is an autoimmune disorder affecting melanocytes in the skin, eyes, inner ear, and meninges. The Epstein-Barr virus and cytomegalovirus (CMV) antigen have been hypothesized as possible triggering factors for the disease. Toll-like receptors (TLRs) play an important role in the induction of defense mechanisms of the innate and adaptive immune responses to microbial pathogens. Among TLRs, TLR9 recognizes unmethylated 2'-deoxyribo (cytidine-phosphate guanosine)(CpG) DNA motifs that are frequently present in viruses and plays a central role in the host defense against viral infection. The aim of this study was to investigate whether TLR9 polymorphisms were associated with VKH in a Japanese population. Methods: Ninety-four Japanese patients diagnosed with VKH and 125 healthy control subjects were recruited. Five single-nucleotide polymorphisms (SNPs: rs187084, rs5743836, rs352139, rs352140, rs5743845) in the TLR9 gene were genotyped, and allelic and phenotypic diversity was assessed between cases and control subjects. Results: Strong linkage disequilibrium was observed among three SNPs (D'' > 0.99), which were located in one haplotype block. Two SNPs (rs5743836 and rs5743845) were monopolymorphic in both cases and controls. No statistically significant association was observed for any of the SNPs between cases and controls. Conclusion: Three SNPs in the TLR9 gene were not significantly associated with susceptibility to VKH.
• [A prospective, observational, all-prescribed-patients study of cyclosporine 0.1% ophthalmic solution in the treatment of vernal keratoconjunctivitis].

  Takamura E, Uchio E, Ebihara N, Okamoto S, Kumagai N, Shoji J, Nakagawa Y, Namba K, Fukushima A, Fujishima H, Miyazaki D, Ohashi Y

  Nippon Ganka Gakkai zasshi 115 508 - 515 6 2011年06月 [査読有り][通常論文]
  
• Toll-like receptor 2 (TLR2) gene polymorphisms are not associated with sarcoidosis in the Japanese population.

  Sato M, Kawagoe T, Meguro A, Ota M, Katsuyama Y, Ishihara M, Namba K, Kitaichi N, Morimoto S, Kaburaki T, Ando Y, Takenaka S, Ohno S, Inoko H, Mizuki N

  Molecular vision 17 731 - 736 2011年03月 [査読有り][通常論文]
  
• Japanese guideline for allergic conjunctival diseases

  Etsuko Takamura, Eiichi Uchio, Nobuyuki Ebihara, Shigeaki Ohno, Yuichi Ohashi, Shigeki Okamoto, Naoki Kumagai, Yoshiyuki Satake, Jun Shoji, Yayoi Nakagawa, Kenichi Namba, Kazumi Fukagawa, Atsuki Fukushima, Hiroshi Fujishima

  Allergology International 60 2 191 - 203 2011年 [査読有り][通常論文]
   

  The definition, classification, pathogenesis, test methods, clinical findings, criteria for diagnosis, and therapies of allergic conjunctival disease are summarized based on the Guidelines for Clinical Management of Allergic Conjunctival Disease (Second Edition) revised in 2010. Allergic conjunctival disease is defined as "a conjunctival inflammatory disease associated with a Type I allergy accompanied by some subjective or objective symptoms." Allergic conjunctival disease is classified into allergic conjunctivitis, atopic keratoconjunctivitis, vernal keratoconjunctivitis, and giant papillary conjunctivitis. Representative subjective symptoms include ocular itching, hyperemia, and lacrimation, whereas objective symptoms include conjunctival hyperemia, swelling, folliculosis, and papillae. Patients with vernal keratoconjunctivitis, which is characterized by conjunctival proliferative changes called giant papilla accompanied by varying extents of corneal lesion, such as corneal erosion and shield ulcer, complain of foreign body sensation, ocular pain, and photophobia. In the diagnosis of allergic conjunctival diseases, it is required that type I allergic diathesis is present, along with subjective and objective symptoms accompanying allergic inflammation. The diagnosis is ensured by proving a type I allergic reaction in the conjunctiva. Given that the first-line drug for the treatment of allergic conjunctival disease is an antiallergic eye drop, a steroid eye drop will be selected in accordance with the severity. In the treatment of vernal keratoconjunctivitis, an immunosuppressive eye drop will be concomitantly used with the abovementioned drugs. ©2011 Japanese Society of Allergology.
• Genome-wide association studies identify IL23R-IL12RB2 and IL10 as Behçet's disease susceptibility loci.

  Mizuki N, Meguro A, Ota M, Ohno S, Shiota T, Kawagoe T, Ito N, Kera J, Okada E, Yatsu K, Song YW, Lee EB, Kitaichi N, Namba K, Horie Y, Takeno M, Sugita S, Mochizuki M, Bahram S, Ishigatsubo Y, Inoko H

  Nature genetics 42 8 703 - U83 8 2010年08月 [査読有り][通常論文]
   

  Behcet's disease is a chronic systemic inflammatory disorder characterized by four major manifestations: recurrent ocular symptoms, oral and genital ulcers and skin lesions(1). We conducted a genome-wide association study in a Japanese cohort including 612 individuals with Behcet's disease and 740 unaffected individuals (controls). We identified two suggestive associations on chromosomes 1p31.3 (IL23R-IL12RB2, rs12119179, P = 2.7 x 10(-8)) and 1q32.1 (IL10, rs1554286, P = 8.0 x 10(-8)). A meta-analysis of these two loci with results from additional Turkish and Korean cohorts showed genome-wide significant associations (rs1495965 in IL23R-IL12RB2, P = 1.9 x 10(-11), odds ratio = 1.35; rs1800871 in IL10, P = 1.0 x 10(-14), odds ratio = 1.45).
• Amelioration of Experimental Autoimmune Uveoretinitis with Nuclear Factor-kappa B Inhibitor Dehydroxy Methyl Epoxyquinomicin in Mice

  Daiju Iwata, Nobuyoshi Kitaichi, Akiko Miyazaki, Kazuya Iwabuchi, Kazuhiko Yoshida, Kenichi Namba, Michitaka Ozaki, Shigeaki Ohno, Kazuo Umezawa, Kenichiro Yamashita, Satoru Todo, Susumu Ishida, Kazunori Onoe

  INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 51 4 2077 - 2084 2010年04月 [査読有り][通常論文]
   

  PURPOSE. Experimental autoimmune uveoretinitis (EAU), a Th1/Th17 cell-mediated autoimmune disease induced in mice, serves as a model of human endogenous uveitis. In this model, proinflammatory cytokines and various stimuli activate the transcriptional factor, nuclear factor-kappa B (NF-kappa B), in the retina. The therapeutic effect of the NF-kappa B inhibitor, dehydroxy methyl epoxyquinomicin (DHMEQ), was examined on EAU. METHODS. EAU was induced in B10.BR mice by K2 peptide immunization. DHMEQ (40 mg/kg/d) was administered daily by intraperitoneal injection. Clinical severity and histopathologic severity were assessed. Translocation of NF-kappa B p65 into the nucleus in EAU retina was assessed. T cells were collected from draining lymph nodes of the K2-immunized mice to examine antigen (Ag)-specific T-cell active responses and cytokine production in vitro. RESULTS. Disease onset was significantly delayed in DHMEQ-treated mice (15.6 days) compared with untreated mice (12.6 days; P < 0.01). Histologic severity was significantly milder in DHMEQ-treated mice (score, 1.13) than in controls (score, 2.33; P < 0.05). DHMEQ suppressed the Ag-specific T-cell active responses and downregulated the productions of Th-1 type cytokines in vitro in a dose-dependent manner. Alternation was not observed in Th-2 type cytokines. Pretreatment of primed T cells or Ag-presenting cells with DHMEQ reduced T-cell activation and Th1/Th17 cytokine production. DHMEQ treatment suppressed the translocation of the NF-kappa B p65 subunit into the nuclei. CONCLUSIONS. Systemic administration of DHMEQ suppressed NF-kappa B translocation in the retina, which might have reduced the inflammation of ocular tissues. DHMEQ-mediated regulation of NF-kappa B p65 could be a therapeutic target for the control of endogenous ocular inflammatory diseases. (Invest Ophthalmol Vis Sci. 2010; 51: 2077-2084) DOI:10.1167/iovs.09-4030
• A Randomized, Placebo-Controlled Clinical Trial of Tacrolimus Ophthalmic Suspension 0.1% in Severe Allergic Conjunctivitis

  Yuichi Ohashi, Nobuyuki Ebihara, Hiroshi Fujishima, Atsuki Fukushima, Naoki Kumagai, Yayoi Nakagawa, Kenichi Namba, Shigeki Okamoto, Jun Shoji, Etsuko Takamura, Kunihiko Hayashi

  JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS 26 2 165 - 173 2010年04月 [査読有り][通常論文]
   

  Aims: To examine the efficacy of tacrolimus ophthalmic suspension 0.1% in treating severe allergic conjunctivitis. Methods: This was a multicenter, randomized, double-masked, placebo-controlled clinical trial. Fifty-six patients with severe allergic conjunctivitis in whom topical antiallergic agents and corticosteroids had been ineffective were randomized to tacrolimus or placebo treatment. Patients were treated either with tacrolimus or placebo twice-daily for 4 weeks. Severity of objective signs in palpebral and bulbar conjunctiva, limbus, and corneal involvement was assessed using 4 grades. Seven subjective symptoms were evaluated by visual analog scale (VAS) assessment. The primary efficacy endpoint was change in the total score of objective signs at the end of treatment. The secondary efficacy endpoints included change in the score for each objective sign and change in the VAS for each subjective symptom. Safety was assessed based on the severity and the incidence of adverse events. Results: Mean change from baseline in total score for objective signs was significantly greater in the tacrolimus (-5.6 +/- 5.1) than in the placebo group (-0.1 +/- 4.5; P < 0.001). Tacrolimus significantly improved giant papillae (P = 0.001) and corneal involvement (P = 0.005). Five subjective symptoms (itching, discharge, hyperemia, lacrimation, and foreign body sensation) were significantly better in the tacrolimus than in the placebo group. The most frequent treatment-related adverse event in the tacrolimus group was mild ocular irritation upon topical instillation, which was well-tolerated. Conclusion: Tacrolimus ophthalmic suspension 0.1% is effective in treating severe allergic conjunctivitis.
• [Infliximab treatment for Behçet's disease--beginning of the biological drug era].

  Namba K

  Nippon Ganka Gakkai zasshi 114 85 - 86 2 2010年02月 [査読有り][通常論文]
  
• Prevention of experimental autoimmune uveoretinitis by blockade of osteopontin with small interfering RNA

  Daiju Iwata, Mizuki Kitamura, Nobuyoshi Kitaichi, Yoshinari Saito, Shigeyuki Kon, Kenichi Namba, Junko Morimoto, Akiko Ebihara, Hirokuni Kitamei, Kazuhiko Yoshida, Susumu Ishida, Shigeaki Ohno, Toshimitsu Uede, Kazunori Onoe, Kazuya Iwabuchi

  EXPERIMENTAL EYE RESEARCH 90 1 41 - 48 2010年01月 [査読有り][通常論文]
   

  Osteopontin (OPN) is elevated during the progression of experimental autoimmune uveoretinitis (EAU) in C57BL/6 (B6) mice. Furthermore, EAU symptoms are ameliorated in OPN knockout mice or in B6 mice treated with anti-OPN antibody (M5). Recently, OPN has been shown to promote the Th1 response not only in the extracellular space as a secretory protein but also in cytosol as a signaling component. Thus, we attempted to reduce OPN in both compartments by using a small interfering RNA (siRNA) targeting the OPN coding sequence (OPN-siRNA). EAU was induced in B6 mice by immunization with human interphotoreceptor retinoid-binding protein (hIRBP) peptide sequence 1-20. The OPN- or control-siRNA was administered with hydrodynamic methods 24 h before and simultaneously with immunization (prevention regimen). When plasma OPN levels were quantified following siRNA administration with the prevention regimen, the level in the OPN-siRNA-treated group was significantly lower than that in the control-siRNA-treated group. Accordingly, the clinical and histopathological scores of EAU were significantly reduced in B6 mice when siRNA caused OPN blockade. Furthermore, TNF-alpha, IFN-gamma, IL-2, GM-CSFand IL-17 levels in the culture supernatants were markedly suppressed in the OPN-siRNA-treated group, whereas the proliferative responses of T lymphocytes from regional lymph nodes against immunogenic peptides was not significantly reduced. On the other hand, the protection was not significant if the mice received the OPN-siRNA treatment on day 7 and day 8 after immunization when the clinical symptoms appeared overt (reversal regimen). Our results Suggest that OPN blockade with OPN-siRNA can be an alternative choice for the usage of anti-OPN antibody and controlling uveoretinitis in the preventive regimen. (C) 2009 Elsevier Ltd. All rights reserved.
• Elevation of surfactant protein D, a pulmonary disease biomarker, in the sera of uveitis patients with sarcoidosis

  Nobuyoshi Kitaichi, Mizuki Kitamura, Kenichi Namba, Susumu Ishida, Shigeaki Ohno

  JAPANESE JOURNAL OF OPHTHALMOLOGY 54 1 81 - 84 2010年01月 [査読有り][通常論文]
   

  Surfactant protein D (SP-D) is found in the epithelial cells of multiple mucosal surfaces. It is commonly used to diagnose and screen for pulmonary diseases. In the present study, serum levels of SP-D were measured in patients with uveitis to ascertain whether SP-D is a clinically useful laboratory parameter to diagnose sarcoidosis. Sera were obtained from 81 patients with sarcoidosis, 16 patients with Beh double dagger et disease, 40 patients with HLA-B27 associated uveitis, 50 patients with Vogt-Koyanagi-Harada (VKH) disease, and 33 healthy volunteers. Serum SP-D levels were quantified with an SP-D enzyme immunoassay kit. In the healthy control subjects, the average serum SP-D level was 39.70 ng/ml; in the uveitis patients with sarcoidosis, the mean serum SP-D level was 57.0 ng/ml, and in the uveitis patients with other etiologies the mean levels were 38.63 ng/ml for Beh double dagger et disease, 38.18 ng/ml for HLA-B27 associated uveitis, and 31.32 ng/ml for the VKH patients. The average serum SP-D levels of patients with sarcoidosis were significantly higher than those of patients with any other uveitis etiologies or healthy controls (P < 0.01). SP-D may be a less invasive and less expensive laboratory examination for sarcoidosis screening. SP-D should be considered as a new laboratory parameter for the diagnosis of uveitis and sarcoidosis.
• Lack of association between toll-like receptor 4 gene polymorphisms and sarcoidosis-related uveitis in Japan

  Yuri Asukata, Masao Ota, Akira Meguro, Yoshihiko Katsuyama, Mami Ishihara, Kenichi Namba, Nobuyoshi Kitaichi, Shin-ichiro Morimoto, Toshikatsu Kaburaki, Yasutaka Ando, Shinobu Takenaka, Hidetoshi Inoko, Shigeaki Ohno, Nobuhisa Mizuki

  MOLECULAR VISION 15 283-88 2673 - 2682 2009年12月 [査読有り][通常論文]
   

  Purpose: Toll-like receptors (TLRs) are pattern-recognition receptors that play an important role in innate and adaptive immune responses to microbial pathogens. Among TLRs, TLR4 recognizes lipopolysaccharides of Gram-negative bacteria. Genetic polymorphisms within the TLR4 gene have been reported to be associated with various inflammatory diseases; therefore, TLR4 appears to be a susceptibility gene for sarcoidosis. Although sarcoidosis has various clinical manifestations, its association with uveitis is more common in Japan than in other countries. The aim of this study was to investigate whether TLR4 polymorphisms were associated with sarcoidosis-related uveitis in a Japanese population. Methods: Two hundred twenty-three patients with sarcoidosis and 206 healthy control subjects were recruited at seven sites in Japan. Eight single-nucleotide polymorphisms (SNPs) in TLR4 were genotyped with a TaqMan assay, and allelic and phenotypic diversity were assessed in affected and control subjects. Results: We found no association with susceptibility to sarcoid-related uveitis for any of the SNPs analyzed. Strong linkage disequilibrium was observed among all the SNPs analyzed (D'=0.78), which were located in one haplotype block. Conclusion: TLR4 polymorphisms do not play an important role in the development of uveitis in Japanese patients with sarcoidosis.
• Clinical features of intraocular inflammation in Hokkaido, Japan

  Hirokuni Kitamei, Nobuyoshi Kitaichi, Kenichi Namba, Satoshi Kotake, Chiho Goda, Mizuki Kitamura, Akiko Miyazaki, Shigeaki Ohno

  ACTA OPHTHALMOLOGICA 87 4 424 - 428 2009年06月 [査読有り][通常論文]
   

  We aimed to investigate the clinical features of intraocular inflammation/uveitis in Hokkaido, Japan. We retrospectively reviewed the medical records of 1240 uveitis patients (511 men, 729 women) who visited Hokkaido University Hospital, Sapporo, Japan between 1994 and 2003. Mean age at disease onset was 41.7 +/- 17.8 years in men and 45.7 +/- 18.3 years in women. Anterior, posterior and combined anterior and posterior segment intraocular inflammation accounted for 45.1%, 4.7% and 50.2% of cases, respectively. Sarcoidosis was the most frequent aetiology (14.9%), followed by Vogt-Koyanagi-Harada (VKH) disease (9.7%) and Behcet's disease (6.7%). Aetiologies in 49.8% patients were unknown. In sarcoidosis, women represented 72.4% of patients, and disease onset occurred at 35.1 +/- 19.0 years of age in men and 50.3 +/- 16.5 years in women. In VKH disease, 54.2% of patients were women, and disease onset took place at 45.9 +/- 15.8 years in men and 46.4 +/- 14.1 years in women. In Behcet's disease, men accounted for 56.6% of patients, and disease onset occurred at 35.5 +/- 8.5 years in men and 44.5 +/- 11.5 years in women. Women were more prone to developing sarcoidosis compared with men. By contrast, men were more prone to developing Behcet's disease. The mean age at disease onset in both sarcoidosis and Behcet's disease was significantly lower in men than in women.
• Association of TLR4 polymorphisms with Behets disease in a Korean population

  Yukihiro Horie, Akira Meguro, Masao Ota, Nobuyoshi Kitaichi, Yoshihiko Katsuyama, Yuko Takemoto, Kenichi Namba, Kazuhiko Yoshida, Yeong Wook Song, Kyung Sook Park, Eun Bong Lee, Hidetoshi Inoko, Nobuhisa Mizuki, Shigeaki Ohno

  RHEUMATOLOGY 48 6 638 - 642 2009年06月 [査読有り][通常論文]
   

  Objectives. HLA-B51 is strongly associated with Behets disease (BD) in any ethnic background. We recently reported that another gene, Toll-like receptor-4 (TLR4) is also implicated in BD in a Japanese population. To confirm these results, we investigated polymorphisms in the TLR4 gene in Korean patients with BD. Methods. In this study, 119 patients with BD and 141 healthy controls were enrolled; every participant was a Korean. Nine single nucleotide polymorphisms previously detected in TLR4 by direct sequencing were analysed for an association with BD. Results. The most frequent haplotype, TAGCGGTAA, was significantly increased in HLA-B51-positive BD patients (49.5), compared with healthy control participants [32.3; P0.029; odds ratio (OR)2.01; 95 CI 1.253.23]. This haplotype was also significantly increased in BD patients with arthritis (48.2; P0.003; OR1.96; 95 CI 1.263.26). There were no significant differences in the allele and genotype frequencies of patients and controls for each single nucleotide polymorphism. Conclusions. The haplotype of TLR4 may increase the risk for developing BD and the complication of arthritis in the Korean population.
• Elevated choroidal blood flow velocity during systemic corticosteroid therapy in Vogt-Koyanagi-Harada disease

  Shigeki Hirose, Wataru Saito, Kazuhiko Yoshida, Michiyuki Saito, Zhenyu Dong, Kenichi Namba, Hisao Satoh, Shigeaki Ohno

  ACTA OPHTHALMOLOGICA 86 8 902 - 907 2008年12月 [査読有り][通常論文]
   

  Laser speckle flowgraphy (LSFG) can be used to non-invasively visualize the haemodynamics of choroidal circulation and the vascular pattern. The purpose of this study was to examine the ability of LSFG to quantitatively evaluate blood flow velocity at the macula in patients with Vogt-Koyanagi-Harada (VKH) disease before and after systemic corticosteroid therapy. Prednisolone (200 mg/day) was systemically administered in 10 VKH disease patients with serous retinal detachment at the macular area. The drug was gradually tapered to zero over a 6-month period. Laser speckle flowgraphy measurements were taken in the 20 eyes of these patients at their initial visit and at 1, 4 and 12 weeks after the onset of therapy. Square blur rate (SBR), a quantitative index of relative blood flow velocity, was calculated using LSFG. Serous retinal detachment resolved within 4 weeks after treatment and visual acuities improved to > 1.0 in almost all cases. There were significant increases in average SBR at the macula at 4 weeks after treatment compared with at 1 week after treatment, and also at 12 weeks after treatment compared with at 4 weeks after treatment. These results suggest that systemic corticosteroid therapy improves inflammation-related impairment in choroidal blood flow velocity at the macula. Laser speckle flowgraphy can evaluate the effect of systemic corticosteroid therapy by enabling comparisons between measurements of blood flow velocity, which is considered to reflect inflammation activity in the choroid.
• Efficacy and complications of intravitreal injection of triamcinolone acetonide for refractory cystoid macular edema associated with intraocular inflammation

  Zhenyu Dong, Kenichi Namba, Nobuyoshi Kitaichi, Chiho Goda, Mizuki Kitamura, Shigeaki Ohno

  JAPANESE JOURNAL OF OPHTHALMOLOGY 52 5 374 - 379 2008年09月 [査読有り][通常論文]
   

  To assess the effects and complications of intravitreal injection of triamcinolone acetonide (IVTA) for posterior sub-Tenon injection of triamcinolone acetonide (PSTA)-resistant cystoid macular edema (CME) with intraocular inflammation. Medical records of eight eyes of six patients with PSTA-resistant CME were retrospectively examined. Each eye received a 4-mg IVTA, and an additional injection was performed when CME recurred. Visual acuity as logarithm of the minimum angle of resolution (logMAR), intraocular pressure (IOP), and central macular thickness (CMT) were assessed before and after each treatment. CME improved in six eyes (75%) with mean visual acuity recovering from 0.56 +/- 0.29 to 0.41 +/- 0.195 (logMAR, P = 0.13) and mean CMT decreasing from 470 mu m (range, 275-660 mu m) to 297 mu m (range, 150-697 mu m) (P = 0.04) 2 months after the initial IVTA. CME recurred an average of 9 months (range, 5-11 months) after IVTA. A higher dose (16-mg) IVTA was effective for two eyes refractory to repeated 4-mg IVTA. IOP was elevated in two eyes (25%), of which one required filtration surgery (12.5%). In phakic eyes, cataracts progressed and necessitated surgery. IVTA is effective for PSTA-resistant CME with intraocular inflammation, and its efficacy might be dose dependent.
• H2-D-d-mediated upregulation of interleukin-4 production by natural killer T-cell and dendritic cell interaction

  Kazuomi Mizuuchi, Yoshiki Yanagawa, Kazuya Iwabuchi, Kenichi Namba, Nobuyoshi Kitaichi, Shigeaki Ohno, Kazunori Onoe

  IMMUNOLOGY 124 1 102 - 111 2008年05月 [査読有り][通常論文]
   

  Natural killer T (NKT) cells are capable of subserving apparently opposite functions, the interferon-gamma (IFN-gamma)-mediated enhancement of host defence and interleukin-4 (IL-4) -mediated immune regulation. Although dendritic cells (DCs) potently activate NKT cells, DC regulation of the IL-4-IFN-gamma balance via NKT-cell activation is not well characterized. In the present study, we examined the effect of DC treatment with CpG oligodeoxynucleotide (ODN), a Toll-like receptor 9 ligand, on the induction of NKT-cell cytokine production. CpG-ODN-conditioned and alpha-galactosylceramide (alpha-GalCer)-loaded myeloid DCs (CpG-DCs) from BALB/c mice showed enhanced ability to induce NKT-cell production of IL-4, but not IFN-gamma, compared to alpha-GalCer-loaded control DCs (not treated with CpG-ODN). The CpG-DCs expressed significantly higher levels of H2-D-d than control DCs, and blocking of the H2-D-d and Ly49 receptor interaction during antigen presentation completely abolished the enhanced ability of the CpG-DCs to induce NKT-cell production of IL-4. These findings demonstrate that DC recognition of the CpG motif leads to induction of enhanced IL-4 production by NKT cells via interaction of the augmented H2-D-d with Ly49 receptors on NKT cells.
• Sister cases of Behcet's disease and Vogt-Koyanagi-Harada disease

  Yukihiro Horie, Kenichi Namba, Nobuyoshi Kitaichi, Shigeaki Ohno

  BRITISH JOURNAL OF OPHTHALMOLOGY 92 3 433 - 434 2008年03月 [査読有り][通常論文]
  
• Polymorphism of IFN-gamma gene and Vogt-Koyanagi-Harada disease

  Yukihiro Horie, Nobuyoshi Kitaichi, Yuko Takemoto, Kenichi Namba, Kazuhiko Yoshida, Shigeto Hirose, Yukiko Hasumi, Masao Ota, Hidetoshi Inoko, Nobuhisa Mizuki, Shigeaki Ohno

  MOLECULAR VISION 13 261-65 2334 - 2338 2007年12月 [査読有り][通常論文]
   

  Purpose: Interferon-gamma (IFN-gamma) is a key cytokine in inflammatory disorders. Elevated aqueous and serum levels of IFN-gamma levels have been reported to be elevated in patients with Vogt-Koyanagi-Harada (VKH) disease. The aim of this study was to determine the IFN-gamma gene polymorphisms in VKH disease. Methods: The study involved 136 VKH patients and 176 healthy controls, who were genotyped for functional single nucleotide polymorphism (SNP; rs2430561; A/T) and functional microsatellite (CA) repeats (rs3138557) in the first intron of the IFN-gamma gene. Moreover, clinical manifestations of the patients were also analyzed. Results: Diffuse choroiditis/staining of fluorescein angiography was seen in all VKH patients in this study. Sunset glow fundus and nummular chorioretinal depigmented scars were observed in 83.9%, and 36.1% of the patients, respectively. Neurological and auditory disorders were observed in 90.1% of the patients: meningismus (79.8%), tinnitus (53.0%), and cerebrospinal fluid pleocytosis (70.0%). Dermatologic manifestations were observed in 22.9% of the patients, manifesting as alopecia (6.9%), poliosis (17.6%), and vitiligo (13.0%). In addition, 22.1% of the patients were classified as having complete VKH disease, while 65.4% as having incomplete VKH disease, and 12.5% as having probable VKH disease. There were no significant differences in the allele and genotype frequencies between VKH patients and healthy controls. In addition, we found no association between each clinical manifestation and SNP (re2430561) in the healthy control subject. A strong linkage disequilibrium (LD) was found in the functional SNP T allele and functional microsatellite 12 (CA) repeats (D' = 0.96-0.99). Conclusions: The functional SNP T allele and microsatellite 12 (CA) repeats were found to have a strong LD, although a genetic susceptibility for the IFN-gamma gene could not be demonstrated among the Japanese VKH patients.
• Osteopontin aggravates experimental autoimmune uveoretinitis in mice

  Mizuki Kitamura, Kazuya Iwabuchi, Nobuyoshi Kitaichi, Shigeyuki Kon, Hirokuni Kitamei, Kenichi Namba, Kazuhiko Yoshida, David T. Denhardt, Susan R. Rittling, Shigeaki Ohno, Toshimitsu Uede, Kazunori Onoe

  JOURNAL OF IMMUNOLOGY 178 10 6567 - 6572 2007年05月 [査読有り][通常論文]
   

  Human endogenous uveitis is a common sight-threatening intraocular inflammatory disease and has been studied extensively using a murine model of experimental autoimmune uveoretinitis (EAU). It is possibly mediated by Th1 immune responses. In the present study, we investigated the role of osteopontin (OPN), a protein with pleiotropic functions that contributes to the development of Th1 cell-mediated immunity. Accompanying EAU progression, OPN was elevated in wild-type (WT) mice that had been immunized with human interphotoreceptor retinoid-binding protein (hIRBP) peptide 1-20. OPN-deficient (OPN-/-) mice showed milder EAU progression in clinical and histopathological scores compared with those of WT mice. The T cells from hIRBPimmunized OPN-/- mice exhibited reduced Ag-specific proliferation and proinflammatory cytokine (TNF-alpha and IFN-,gamma) production compared with those of WT T cells. When hIRBP-immunized WT mice were administered M5 Ab reacting to SLAYGLR sequence, a cryptic binding site to integrins within OPN, EAU development was significantly ameliorated. T cells from hIRBPimmunized WT mice showed significantly reduced proliferative responses and proinflammatory cytokine production upon stimulation with hIRBP peptide in the presence of M5 Ab in the culture. Our present results demonstrate that OPN may represent a novel therapeutic target to control uveoretinitis. The Journal of Immunology, 2007, 178: 6567-6572.
• Genetic polymorphisms in the promoter of the interferon gamma receptor 1 gene are associated with atopic cataracts

  Akira Matsuda, Nobuyuki Ebihara, Naoki Kumagai, Ken Fukuda, Koji Ebe, Koji Hirano, Chie Sotozono, Mamoru Tei, Koichi Hasegawa, Makiko Shimizu, Mayumi Tamari, Kenichi Namba, Shigeaki Ohno, Nobuhisa Mizuki, Zenro Ikezawa, Taro Shirakawa, Junji Hamuro, Shigeru Kinoshita

  INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 48 2 583 - 589 2007年02月 [査読有り][通常論文]
   

  PURPOSE. Previous reports have shown genetic predisposition for atopic dermatitis ( AD). Some of the severe complications of AD manifest in the eye, such as cataract, retinal detachment, and keratoconjunctivitis. This study was conducted to examine the genetic association between the atopy-related genes and patients with ocular complications ( ocular AD). METHODS. Seventy-eighty patients with ocular AD and 282 healthy control subjects were enrolled in an investigation of the association between the atopy-related genes ( FCERB, IL13, and IFNGR1) and ocular AD. Genetic association studies and functional analysis of single nucleotide polymorphisms ( SNPs) were performed. RESULTS. The -56TT genotype in the IFNGR1 promoter region was significantly associated with an increased risk of ocular AD under recessive models ( chi(2) test, raw P = 0.0004, odds ratio 2.57). The -56TT genotype was more common in atopic cataracts. A reporter gene assay showed that, after stimulation with IFN-gamma, the IFNGR1 gene promoter construct that contained the -56T allele, a common allele in ocular AD patients, manifested higher transcriptional activity in lens epithelial cells ( LECs) than did the construct with the -56C allele. Real-time PCR analysis demonstrated higher IFNGR1 mRNA expression in the LECs in atopic than in senile cataracts. iNOS expression by IFNGR1-overexpressing LECs was enhanced on stimulation with IFN-gamma and LPS. CONCLUSIONS. The -56T allele in the IFNGR1 promoter results in higher IFNGR1 transcriptional activity and represents a genetic risk factor for atopic cataracts.
• Association of heat shock protein 70 induction and the amelioration of experimental autoimmune uveoretinitis in mice

  Hirokuni Kitamei, Nobuyoshi Kitaichi, Kazuhiko Yoshida, Akira Nakai, Mitsuaki Fujimoto, Mizuki Kitamura, Kazuya Iwabuchi, Akiko Miyazaki, Kenichi Namba, Shigeaki Ohno, Kazunori Onoe

  IMMUNOBIOLOGY 212 1 11 - 18 2007年 [査読有り][通常論文]
   

  Experimental autoimmune uveoretinitis (EAU) serves as a model of human endogeneous uveitis. In the present study we examined whether induction of heat shock protein (HSP) 70 by oral geranylgeranyl acetone (GGA) administration had a therapeutic effect on murine EAU. When C57BL/6 mice that had received oral administration of GGA (500mg/kg) were immunized with interphotoreceptor retinoid-binding protein (IRBP)-derived peptide plus adjuvants, the expression levels of HSP70 mRNA and protein were rapidly and transiently upregulated in eyes of the GGA-treated mice, compared with those from vehicle-pretreated and IRBP-immunized mice. The antigen-specific T cell proliferation was partially suppressed in these mice treated with GGA. The mean EAU scores of the GGA-treated mice on day 21 and 28 (2.4 +/- 0.2 and 2.1 +/- 0.2, respectively) were significantly lower than those in the controls (3.0 +/- 0.1 and 2.6 +/- 0.2, respectively p < 0.01). The histopathological severity of the GGA-treated mice (average 0.33) was markedly milder than that in the controls (average 1.63, p < 0.05) at day 21. The present findings demonstrate that the pharmacological induction of HSP70 may be applicable to the amelioration of ocular autoimmune diseases. (c) 2006 Elsevier GmbH. All rights reserved.
• Repeated exacerbations of ocular inflammation with vitreous hemorrhage in a patient with HLA-B27 associated uveitis

  Satoru Kase, Kenichi Namba, Yukihiro Horie, Satoshi Kotake, Shigeaki Ohno

  Journal of Medical Investigation 54 3-4 350 - 353 2007年 [査読有り][通常論文]
   

  HLA-B27 associated uveitis is characterized by recurrent alternating acute unilateral attacks of intraocular inflammation in the anterior chamber. The aim of this study was to report an unusual case of repeated exacerbations with vitreous hemorrhage in HLA-B27 associated uveitis. Thirty four-year-old man was diagnosed as HLA-B27 associated uveitis in his right eye. He showed repeated exacerbation of ocular inflammation with retinal vein dilation and small retinal hemorrhage following vitreous hemorrhage. Fluorescein fundus angiography a week before the appearance of vitreous hemorrhage showed no neovascularization. Oral prednisolone administration was started from 40 mg/day with gradual tapering. About 3 weeks after the onset, most of the vitreous hemorrhage disappeared and visual acuity was improved to 20/20. Through the decreased vitreous hemorrhage, Weiss ring was detected later. The vitreous hemorrhage found in this patient is a severe exacerbation, and might be a consequence of the vitritis that leads to posterior vitreous detachment.
• Elevation of serum Krebs von den Lunge-6 levels in patients with tubulointerstitial nephritis and Uveitis syndrome

  Satoru Kase, Nobuyoshi Kitaichi, Kenichi Namba, Akiko Miyazaki, Kazuhiko Yoshida, Kenji Ishikura, Masahiro Ikeda, Taiji Nakashima, Shigeaki Ohno

  AMERICAN JOURNAL OF KIDNEY DISEASES 48 6 935 - 941 2006年12月 [査読有り][通常論文]
   

  Background Tubulointerstitial nephritis and uveitis (TINU) syndrome is characterized by a combination of idiopathic acute tubulointerstitial nephritis and uveitis. Krebs von den Lunge-6 (KL-6) is a human glycoprotein secreted by type II alveolar cells in the lung, and its serum levels increase in patients with pneumonia of various causes, as well as ocular sarcoidosis. The aim of the present study is to quantify serum KL-6 levels in patients with TINU syndrome, which has no pulmonary and sarcoid lesions, and elucidate the usefulness of KL-6 for the diagnosis and follow-up of this syndrome. Methods: Serum and urinary samples were obtained from 17 patients with TINU syndrome and 36 age-matched patients with uveitis from other causes. Sarcoidosis was eliminated because serum KL-6 levels increased during their lung lesion. Serum KL-6 level was determined by using a human KL-6 electrochemiluminescence immunoassay. Formalin-fixed paraffin-embedded renal tissue sections were incubated with anti-KL-6 monoclonal antibody, then examined immunohistochemically. Results: Mean serum KL-6 levels for patients with TINU syndrome and those with uveitis from other causes were 363.35 +/- 51.06 and 213.19 +/- 10.28 U/mL, respectively (P < 0.001). Urinary beta(2)-Microglobulin levels of patients with TINU syndrome and uveitis from other causes were 4.06.+/- 1.31 and 0.16 +/- 0.20 mg/L, respectively (P < 0.001). All patients with TINU syndrome showed a simultaneous decrease in serum KL-6 and urinary beta(2)-Microglobulin levels after the beginning of treatment. Strong immunoreactivity for KL-6 was observed in renal distal tubules in biopsy tissue of patients with TINU syndrome. Conclusion: We show a significant increase in serum KL-6 levels in patients with TINU syndrome, whereas levels were normal in patients with other causes of uveitis without nephritis. Renal distal tubules stained strongly with anti-KL-6 antibody, suggesting that high KL-6 levels may reflect the renal lesion of TINU syndrome. Serum KL-6 may be a potential laboratory parameter for the diagnosis and follow-up of patients with TINU syndrome that could complement urinary beta(2)-Microglobulin measurements.
• Tyrosinase gene family and Vogt-Koyanagi-Harada disease in Japanese patients

  Yukihiro Horie, Yuko Takemoto, Akiko Miyazaki, Kenichi Namba, Satoru Kase, Kazuhiko Yoshida, Masao Ota, Yukiko Hasumi, Hidetoshi Inoko, Nobuhisa Mizuki, Shigeaki Ohno

  MOLECULAR VISION 12 182-86 1601 - 1605 2006年12月 [査読有り][通常論文]
   

  Purpose: The aim of the present study was to examine the genetic background of Vogt-Koyanagi-Harada (VKH) disease in a Japanese population by analyzing the tyrosinase gene family (TYR, TYRP1, and dopachrome tautomerase (DCT)). Methods: 87 VKH patients and 122 healthy controls were genotyped using seven microsatellite markers on the candidate loci. We analyzed microsatellite (MS) polymorphisms at regions within tyrosinase gene family loci. In addition, the haplotype frequencies were also estimated and statistical analysis was performed. HLA-DRB1 genotyping was performed by the PCR-restriction fragment length polymorphism (RFLP) method. Results: No significant evidence for an association was found. HLA-DRB1*0405 showed a highly significant association with VKH disease compared with the healthy controls (Pc=0.000000079), as expected. Conclusions: We concluded that there is no genetic susceptibility or increased risk attributed to the tyrosinase gene family. Our results suggest the need for further genetic study and encourage a search for novel genetic loci and predisposing genes in order to elucidate the genetic mechanisms underlying VKH disease.
• Chronic panuveitis and scleritis in a patient with cryptogenic organizing pneumonia

  Wataru Saito, Akari Saito, Kenichi Namba, Satoru Kase, Masanori Shiratori, Shigeaki Ohno

  JAPANESE JOURNAL OF OPHTHALMOLOGY 50 6 558 - 561 2006年11月 [査読有り][通常論文]
  
• Granulocytapheresis in patients with refractory ocular Behcet's disease

  Kenichi Namba, Koh-Hei Sonoda, Hirokuni Kitamei, Kenji Shiratori, Akiko Ariyama, Kazuya Iwabuchi, Kazunori Onoe, Abby R. Saniabadi, Shoichi Inaba, Tatsuro Ishibashi, Shigeaki Ohno

  JOURNAL OF CLINICAL APHERESIS 21 2 121 - 128 2006年07月 [査読有り][通常論文]
   

  Intraocular inflammation (uveoretinitis) is one major complication of Behcet's disease (BD) and responds poorly to drug therapy. This open prospective study was to assess the efficacy of selective granulocytapheresis in patients with refractory uveoretinitis of BD. Fourteen patients aged 20-56 years were treated. Granulocytapheresis was done with an Adacolumn filled with cellulose acetate leucocyte carries or beads that adsorb granulocytes and monocytes from the blood in the column. Each patient received 5 Adacolumn sessions at one session/week over 5 consecutive weeks. The study was designed to allow each patient to serve as his or her own control. The total numbers of ocular attacks (OA) were monitored for 6 months before and after 5 Adacolumn sessions. The number of OA (mean SD) per patient for the 6 months before Adacolumn was 4.21 +/- 1.6 and for the 6 months post Adacolumn was 2.93 +/- 1.39 (P = 0.0275). Nine patients (64%) improved and 5 did not change or worsened. Further, for a sub-group (n = 7) with duration of BD >= 5 years, the number of OA were 4.71 +/- 1.89 for the first 6 months and 2.29 +/- 1.38 for the second 6 months (P = 0.0054). The corresponding values for a sub-group (n = 7) with duration of BD < 5 years were 3.71 +/- 1.25 and 3.57 +/- 1.13, indicating that patients with long duration of BD are better responders. We conclude that granulocytapheresis might be effective and safe for patients with refractory ocular BD. Further studies are necessary to fully evaluate the clinical efficacy of granulocytapheresis for BD.
• Amelioration of experimental autoimmune uveoretinitis (EAU) with an inhibitor of nuclear factor-kappa B (NF-kappa B), pyrrolidine dithiocarbamate

  Hirokuni Kitamei, Kazuya Iwabuchi, Kenichi Namba, Kazuhiko Yoshida, Yoshiki Yanagawa, Nobuyoshi Kitaichi, Mizuki Kitamura, Shigeaki Ohno, Kazunori Onoe

  JOURNAL OF LEUKOCYTE BIOLOGY 79 6 1193 - 1201 2006年06月 [査読有り][通常論文]
   

  Experimental autoimmune uveoretinitis (EAU) is a T helper type I cell-mediated autoimmune disease, which serves as a model of human chronic uveitis. In this model, cells of a monocyte/ macrophage lineage and retinal antigen (Ag)-specific T cells infiltrate into the retina and cause inflammatory lesion, where proinflammatory cytokines and various stimuli activate a transcriptional factor, nuclear factor-kappa B (NF-kappa B), which modulates inflammation and enhances immune responses. In the present study, the therapeutic effect of administration of a NF-kappa B inhibitor, pyrrolidine dithiocarbamate (PDTC), was examined in a murine EAU model. It was shown that PDTC ameliorated the clinical symptoms of EAU mice and significantly reduced the histopathological score compared with those in untreated mice. mRNA expressions of tumor necrosis factor alpha and interleukin-1 beta were suppressed in eyes of PDTC-treated EAU juice. However, when T cells from PDTC-treated EAU mice, Ag-presenting cells (APC), and the retinal Ag peptides were cocultured, these T cells showed the same level of proliferation as those from control mice. Furthermore, addition of PDTC in the culture of T cells from EAU mice, Ag, and APC completely abrogated the T cell-proliferative response and cytokine production. Pretreatment of Ag-primed T cells or APC with PDTC in vitro also reduced these responses. These results indicate that the inhibitory effect of PDTC is attributed mainly to the suppression of effector-phase responses including inflammation but not to the inhibition of T cell priming. Regulation of NF-kappa B pathway in the lesion could be a novel target for the successful control of uveoretinitis.
• Usefulness of quantifying serum KL-6 levels in the follow-up of uveitic patients with sarcoidosis

  N Kitaichi, T Ariga, S Kase, K Yoshida, K Namba, S Ohno

  GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY 244 4 433 - 437 2006年04月 [査読有り][通常論文]
   

  Background: KL-6 is a human glycoprotein secreted by type II alveolar cells in the lung, and its serum levels increase in pneumonia of various causes. We previously reported that serum KL-6 levels in uveitis patients with sarcoidosis were significantly higher than those of other uveitis patients and healthy controls. Additionally, the combined measurement of serum KL-6 and angiotensin converting enzyme (ACE) was useful for screening uveitic patients to diagnose sarcoidosis. The purpose of the present study was to investigate the clinical usefulness of quantifying serum KL-6 levels for following-up the patients with sarcoidosis. Methods: Sera were obtained from 36 uveitic patients diagnosed with sarcoidosis and the same number of healthy volunteers. To examine the influence of systemic medication, we also collected blood samples from four more sarcoidosis patients, who were systemically treated with corticosteroid or angiotensin converting enzyme (ACE) inhibitor, an anti-hypertensive drug. The serum concentration of KL-6 was measured by a human KL-6 electrochemiluminescence immunoassay (ECLIA). Results: The mean KL-6 concentrations of sarcoidosis patients and healthy controls were 449.3 +/- 66.3 (mean +/- SE) and 192.1 +/- 11.3, respectively. The average levels of serum KL-6 were significantly elevated in sarcoidosis patients compared with healthy control subjects (P < 0.001), and there were significant correlations between serum KL-6 and ACE levels in the patients with sarcoidosis (r=0.70 and P < 0.0001). Moreover, serum KL-6 concentrations were less affected by systemic corticosteroid, and unaffected by ACE inhibitory drugs in contrast to ACE levels. Conclusions: Measurement of serum KL-6 in the uveitic patients may be useful to follow-up the diagnosed sarcoidosis, as well as for diagnosing sarcoidosis, because the serum KL-6 level was well correlated with the ACE level, and less affected by systemic medication than ACE levels.
• Clinical features in tubulointerstitial nephritis and uveitis (TINU) syndrome

  C Goda, S Kotake, A Ichiishi, K Namba, N Kitaichi, S Ohno

  AMERICAN JOURNAL OF OPHTHALMOLOGY 140 4 637 - 641 2005年10月 [査読有り][通常論文]
   

  PURPOSE: To analyze clinical features of the tubulointerstitial nephritis and uveitis (TINU) syndrome in Japan, especially exacerbations or recurrences of uveitis. DESIGN: Retrospective observational study. METHODS: We reviewed the clinical features in 12 patients with TINU syndrome diagnosed by renal biopsy, who were evaluated and treated at the Department of Ophthalmology, Hokkaido University Hospital. Visual acuity was measured using decimal visual acuity. RESULTS: Patient age ranged from 10 to 33 years (mean 21 years), and females accounted for 83% of the cases. Both eyes were affected in 11 patients (92%). All 12 patients initially experienced ocular symptoms, with hyperemia being the chief complaint. We diagnosed patients as having uveitis and conducted blood tests and urinalysis. Urinalysis did show characteristic findings, most notably glucosuria, increased beta 2 microglobulin that were >= 10 times that of normal levels, and increased N-acetylglucosaminidose levels in a high percentage of patients. Recurrent or exacerbating uveitis was seen in six patients (50%). In exacerbated or recurrent uveitis, inflammation was more severe (>= 3 + cells of the anterior eye segment). The ocular inflammation generally responded well to treatment with oral corticosteroids, and the number of recurrences was lower at corticosteroid doses of :prednisolone 40 mg. CONCLUSIONS: Ophthalmologists play an important role in the initial discovery of patients with TINU syndrome. Because inflammation was more severe in exacerbated or recurrent uveitis, in instances where uveitis is refractory to local therapy, oral corticosteroids should be considered as early as possible. (Am J Ophthalmol 2005. (c) 2005 by Elsevier Inc. All rights reserved.)
• Expression of thymidine phosphorylase in choroidal malignant melanoma associated with neovascular glaucoma

  S Kase, W Saito, K Yoshida, K Namba, M Osaki, K Ohgami, K Shiratori, N Kitaichi, H Adachi, H Ito, S Ohno

  PATHOLOGY INTERNATIONAL 55 9 569 - 573 2005年09月 [査読有り][通常論文]
   

  Reported herein is a case of 62-year-old man who complained of blurred vision and ocular pain in his right eye. The patient was diagnosed with choroidal melanoma complicated by neovascular glaucoma (NVG) and total retinal detachment, and he underwent enucleation of the eye. The isolated tumor was 2.5 x 2.5 cm in size. It was accompanied by intratumoral calcification, and consisted of epithelioid and spindle melanoma cells. There were a variety of microvessels in the stroma of the iris. The expression of thymidine phosphorylase (dThdPase), an angiogenic factor, was examined immunohistochemically. Cytoplasmic immunoreactivity for dThdPase was more prominent in the epithelioid cells than in spindle tumor cells. Another case of choroidal melanoma without NVG had less marked immunoreactivity. These results suggest that the production of dThdPase by melanoma cells correlates with the pathogenesis of NVG.
• Comparative study of two sets of criteria for the diagnosis of Vogt-Koyanagi-Harada's disease

  M Kitamura, K Takami, N Kitachi, K Namba, H Kitamei, S Kotake, S Ohno

  AMERICAN JOURNAL OF OPHTHALMOLOGY 139 6 1080 - 1085 2005年06月 [査読有り][通常論文]
   

  PURPOSE: The Vogt-Koyanagi-Harada's (VKH) Dis- ease Committee established the "Revised diagnostic criteria for VKH disease" in 2001. The purpose of the present study was to assess the concordance between these criteria and the traditional Sugiura's diagnosis system. DESIGN: Observational case series. METHODS: The medical records of patients previously diagnosed with VKH disease based upon Sugiura's criteria at the Uveitis Survey Clinic of the Hokkaido University Hospital between 1991 and 2003 were retrospectively reevaluated using the VKH Committee's revised diagnostic criteria for VKH disease. RESULTS: Sugiura's criteria were used to identify 169 patients with VKH disease. All patients were Japanese, and 95 cases (56%) were women. Mean age at the time of their first visit to our clinic was 44.7 +/- 13.9 years (range, 9 to 74 years). Using the VKH Committee's new criteria, 91.7% of the previously diagnosed VKH patients were classified as having the disease. Of this group, 11.8% were classified as complete, 71% incomplete, and 8.9% as probable VKH disease. CONCLUSIONS: The VKH Committee's revised diagnostic criteria proved useful for VKH disease diagnosis, as the concordance rate for the two criteria was more than 90%. However, patients who had prior cataract surgery or who lacked signs of serous retinal detachment were not classified as having VKH disease because of exclusion by the VKH Committee's new criteria. (c) 2005 by Elsevier Inc. All rights reserved.
• Inducible immune regulation following autoimmune disease in the immune-privileged eye

  N Kitaichi, K Namba, AW Taylor

  JOURNAL OF LEUKOCYTE BIOLOGY 77 4 496 - 502 2005年04月 [査読有り][通常論文]
   

  The immune-privileged eye has the potential to induce regulatory immunity along with local mechanisms of immunosuppression. Rodent models of human antoimmune uveoretinitis [experimental antoimmune uveoretinitis (EAU)] recover without spontaneous recurrence of uveitis, which differs from uveitis in some humans. This raises the possibility that the mechanism of immune privilege in the rodent eye can reimpose itself during autoimmune uveoretinitis and re-establish tolerance to antoantigen. To investigate this possibility, we examined the spleens of EAU-recovered mice for regulatory immunity. We detected regulatory immunity when we adoptively transferred post-EAU spleen cells into other mice immunized for EAU. We could not detect this regulatory immunity in enucleated mice nor in naive mice. Moreover, unlike the mechanisms of anterior chamber-associated immune deviation, the suppression was only mediated by post-EAU CD4(+) T cells, which required activation with antoantigen presented by post-EAU spleen antigen-presenting cells (APC). Our results demonstrate that when the immune-privileged ocular microenvironment recovers from an autoimmune response, it has influenced systemic immunity to retinal antoantigen by affecting APC and mediating induction of potential regulatory CD4+ T cells laying in wait in the post-EAU spleen for restimulation.
• Increase of KL-6 in sera of uveitis patients with sarcoidosis

  N Kitaichi, S Kotake, H Shibuya, Y Yamada, H Chiba, K Namba, S Ohno

  GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY 241 11 879 - 883 2003年11月 [査読有り][通常論文]
   

  Background. KL-6 is a human glycoprotein secreted by type II alveolar cells in lung, and its serum levels increase in pneumonia of various causes. KL-6 is a member of the MUC-1 family, which is expressed in lung, cornea, and conjunctiva. The purpose of the present study was to investigate the clinical usefulness of quantifying serum KL-6 levels for diagnosing sarcoidosis in patients with uveitis. Methods. Sera were obtained from 24 uveitis patients diagnosed with sarcoidosis, 37 uveitis patients with other etiologies, and 138 healthy control subjects. Serum concentration of KL-6 was determined by a human KL-6 electrochemiluminescence immunoassay. Results. The average level of KL-6 in the sera of uveitis patients with sarcoidosis was 387 U/ml. This was significantly higher than in healthy subjects and uveitis patients with other etiologies. The KL-6 measurements identified 45.8% of sarcoidosis-positive patients. When the KL-6 results were combined with serum angiotensin-converting enzyme (ACE) concentrations, 87.5% of sarcoidosis patients were identified, compared to 66.7% using ACE results alone. The combined measurement identified 10.8% of the non-sarcoid patients and 0.72% of healthy subjects as positive (false positive). Conclusion. Combined measurements of serum KL-6 and ACE may be useful as a screening for sarcoidosis in uveitis patients.
• The change of clinical manifestations of patients with Behçet's disease in Japan.

  Kotake S, Namba K, Higashi K, Goda C, Ariga T, Ogawa A, Ohno S

  Advances in experimental medicine and biology 528 83 - 84 2003年 [査読有り][通常論文]
  
• Induction of regulatory T cells by the immunomodulating cytokines alpha-melanocyte-stimulating hormone and transforming growth factor-beta 2

  K Namba, N Kitaichi, T Nishida, AW Taylor

  JOURNAL OF LEUKOCYTE BIOLOGY 72 5 946 - 952 2002年11月 [査読有り][通常論文]
   

  Recently, we have reported that the cytokines alpha-melanocyte-stimulating hormone (alpha-MSH) and transforming growth factor-beta2 (TGF-beta2) work in synergy to induce the activation of regulatory T (Treg) cells. When we used (alpha-MSH and TGF-beta2 to generate ocular antoantigen-specific Treg cells and adoptively transferred them into mice susceptible to experimental autoimmune uveoretinitis (EAU), there was suppression in the incidence and severity of EAU. Specificity to a retinal autoantigen was required for the Treg cells to suppress EAU. When stimulated, these Treg cells produced TGF-beta1, and their production of interferon-gamma, interleukin (IL)-10, and IL-4 was suppressed. Also, the Treg cells are suppressed in their proliferative response. Our results demonstrate that alpha-MSH with TGF-beta2 induce Treg cells that can subdue a tissue-specific autoimmune response. This also promotes the possibility of using these immono-modulating cytokines to purposely induce antigen-specific Treg cells to prevent and suppress antoimmune disease.

MISC

• 【わかりやすい感覚器疾患】 感覚器の構造と機能 視覚 虹彩・隅角

  南場 研一 日本医師会雑誌 147 (特別1) S42 -S43 2018年06月 [査読無し][通常論文]
  
• トリアムシノロンTenon嚢下注射で悪化し、眼内液を用いたPCR法が診断に有用であった眼トキソプラズマ症の1例

  丸茂 有香, 水谷 武史, 加藤 亜紀, 野崎 実穂, 吉田 宗徳, 南場 研一, 小椋 祐一郎 あたらしい眼科 35 (6) 815 -819 2018年06月 [査読無し][通常論文]
   

  目的:トリアムシノロンTenon嚢下注射により悪化し、硝子体液PCRにより眼トキソプラズマ症と診断された1例を経験したので報告する。症例:55歳、女性。2000年に左眼のトキソプラズマ症に対しアセチルスピラマイシン内服、2008年に左眼ぶどう膜炎および視神経炎に対しステロイド内服の既往があった。2015年7月に左眼難治性ぶどう膜炎の精査加療目的で名古屋市立大学病院を受診した。初診時、左眼に硝子体混濁、および限局性網膜滲出斑を認めた。ぶどう膜炎に対しステロイド内服を行ったが所見が改善しないため、2015年8月および11月にトリアムシノロンTenon嚢下注射を施行したところ炎症が悪化した。翌年3月に左眼硝子体手術を施行、硝子体液のPCR検査でトキソプラズマDNAが確認された。眼トキソプラズマ症と診断しクリンダマイシン内服治療開始、その後硝子体混濁、網脈結膜炎は改善した。結論:診断確定にはPCR法によるトキソプラズマ原虫ゲノムの検査が有用である。(著者抄録)
• PM2.5汚染は重症アレルギー性結膜疾患と関連する

  宮崎 大, 深川 和己, 福島 敦樹, 藤島 浩, 内尾 英一, 海老原 伸行, 庄司 純, 高村 悦子, 南場 研一, 大橋 裕一, 岡本 茂樹, 佐竹 良之, 大津 洋 アレルギー 67 (4-5) 590 -590 2018年05月 [査読無し][通常論文]
  
• 日本の眼科医および家族におけるアレルギー性結膜疾患の有病率調査

  深川 和己, 宮崎 大, 福島 敦樹, 藤島 浩, 内尾 英一, 海老原 伸行, 庄司 純, 高村 悦子, 南場 研一, 大橋 裕一, 岡本 茂樹, 佐竹 良之, 大津 洋 アレルギー 67 (4-5) 670 -670 2018年05月 [査読無し][通常論文]
  
• 経過中ぶどう膜炎を併発した尋常性乾癬の小児の1例

  宮澤 元, 藤田 靖幸, 村松 憲, 岩田 浩明, 南場 研一, 保科 大地, 清水 宏 日本皮膚科学会雑誌 128 (4) 608 -608 2018年04月 [査読無し][通常論文]
  
• TNF阻害薬の医師基準・施設基準および導入前スクリーニング検査

  南場 研一 日本眼科学会雑誌 122 (臨増) 96 -96 2018年03月 [査読無し][通常論文]
  
• 日本におけるアレルギー性結膜疾患の有病率と実態調査

  宮崎 大, 深川 和巳, 福島 敦樹, 藤島 浩, 内尾 英一, 海老原 伸行, 庄司 純, 高村 悦子, 南場 研一, 大橋 裕一, 岡本 茂樹, 佐竹 良之, 大津 洋 日本眼科学会雑誌 122 (臨増) 178 -178 2018年03月 [査読無し][通常論文]
  
• 眼サルコイドーシスの診断における血液検査・画像検査の有用性

  鈴木 佳代, 南場 研一, 水内 一臣, 岩田 大樹, 福原 崇子, 長谷 敬太郎, 濱田 怜, 大野 重昭, 北市 伸義, 石田 晋 日本眼科学会雑誌 122 (臨増) 191 -191 2018年03月 [査読無し][通常論文]
  
• 【脈絡膜疾患:ここまで解明できる!】 白点症候群

  岩田 大樹, 南場 研一 あたらしい眼科 34 (12) 1725 -1730 2017年12月 [査読無し][通常論文]
  
• フォークト・小柳・原田病の発症年齢における脈絡膜形態および循環動態の検討

  橋本 勇希, 南場 研一, 廣岡 季里子, 水内 一臣, 岩田 大樹, 石田 晋 日本視能訓練士協会誌 46 309 -309 2017年12月 [査読無し][通常論文]
  
• トリアムシノロンテノン嚢下注射で急速に増悪した眼トキソプラズマ症の一例

  丸茂 有香, 水谷 武史, 加藤 亜紀, 野崎 実穂, 吉田 宗徳, 南場 研一, 小椋 祐一郎 眼科臨床紀要 10 (11) 965 -965 2017年11月 [査読無し][通常論文]
  
• 【眼科救急Q&A】 救急疾患ごとの基本的な対処法 ぶどう膜炎 Vogt-小柳-原田病の初発症状、鑑別、治療について教えてください

  岩田 大樹, 南場 研一 あたらしい眼科 34 (臨増) 187 -189 2017年11月 [査読無し][通常論文]
  
• トリアムシノロンテノン嚢下注射で急速に増悪した眼トキソプラズマ症の一例

  丸茂 有香, 水谷 武史, 加藤 亜紀, 野崎 実穂, 吉田 宗徳, 南場 研一, 小椋 祐一郎 眼科臨床紀要 10 (11) 965 -965 2017年11月 [査読無し][通常論文]
  
• ステロイドを用いないタクロリムス点眼治療のシールド潰瘍に対する有効性

  宮崎 大, 井上 幸次, 福島 敦樹, 大橋 裕一, 海老原 伸行, 内尾 英一, 岡本 茂樹, 庄司 純, 高村 悦子, 中川 やよい, 南場 研一, 藤島 浩 眼科臨床紀要 10 (9) 770 -770 2017年09月 [査読無し][通常論文]
  
• Rosai-Dorfman病に合併した続発緑内障に対し360.suture trabeculotomy変法が奏効した1例

  菊地 香澄, 木嶋 理紀, 新明 康弘, 大口 剛司, 陳 進輝, 南場 研一, 齋藤 航, 石田 晋 眼科手術 30 (3) 514 -517 2017年07月 [査読無し][通常論文]
   

  背景:Rosai-Dorfman病(RDD)は1969年にRosaiとDorfmanによって報告された非腫瘍性組織球増殖性疾患であり、無痛性の頸部リンパ節腫脹で発症することが多く、約半数に節外病変を生じる。節外病変としてぶどう膜炎の報告が17例あるが、その続発緑内障に対しtrabeculotomy(LOT)を施行した報告はない。今回、筆者らはRDDに合併したぶどう膜炎治療中に続発緑内障をきたし、半年以上眼圧の改善がみられなかった症例に対し、360.suture trabeculotomy変法(S-LOT)を施行し、良好な眼圧コントロールが得られた1例を経験したので報告する。症例:63歳、女性。ぶどう膜炎精査加療目的で近医より紹介。所見:両眼に汎ぶどう膜炎を認め、精査にても確定診断には至らなかった。ステロイドの内服と点眼、Tenon嚢下注射にて加療し、眼圧は正常範囲内で経過していた。初診から7年後に腎腫瘍・骨腫瘍を指摘され、生検の結果RDDと診断された。初診から10年後に両眼圧は右眼46mmHg、左眼32mmHgと上昇し、前房に炎症所見はなく、緑内障点眼やアセタゾラミドナトリウム内服にてもコントロール不良であったため、両眼にS-LOTを施行した。術後2年間にわたり、眼圧は右眼10〜16mmHg、左眼9〜13mmHgと良好であった。結論:RDDに合併したぶどう膜炎治療中に発症した続発緑内障に対し、S-LOTが有効である可能性が示唆された。(著者抄録)
• Vogt・小柳・原田病の再発の有無によるステロイド全身投与後の脈絡膜循環動態の比較

  廣岡 季里子, 齋藤 航, 南場 研一, 水内 一臣, 岩田 大樹, 橋本 勇希, 齋藤 理幸, 石田 晋 眼科臨床紀要 9 (10) 842 -843 2016年10月 [査読無し][通常論文]
  
• タクロリムス点眼によるステロイド反応性眼圧上昇抑制効果

  宮崎 大, 井上 幸次, 福島 敦樹, 大橋 裕一, 海老原 伸行, 内尾 英一, 岡本 茂樹, 庄司 純, 高村 悦子, 中川 やよい, 南場 研一, 藤島 浩 眼科臨床紀要 9 (6) 539 -540 2016年06月 [査読無し][通常論文]
  
• ゲノムワイド関連解析を用いた眼サルコイドーシス感受性遺伝子のスクリーニング

  石原 麻美, 目黒 明, 南場 研一, 大野 重昭, 蕪城 俊克, 高瀬 博, 望月 學, 後藤 浩, 竹内 大, 堀 純子, 北市 伸義, 水木 信久 日本眼科学会雑誌 120 (臨増) 223 -223 2016年03月 [査読無し][通常論文]
  
• Vogt-小柳-原田病再発例に対するシクロスポリン併用療法の検討

  水内 一臣, 南場 研一, 岩田 大樹, 宇野 友絵, 北市 伸義, 大野 重昭, 石田 晋 日本眼科学会雑誌 119 (臨増) 187 -187 2015年03月 [査読無し][通常論文]
  
• アレルギー性結膜疾患診断における自覚症状, 他覚所見および涙液総IgE検査キットの有用性の検討

  庄司 純, 内尾 英一, 海老原 伸行, 大橋 裕一, 大野 重昭, 岡本 茂樹, 熊谷 直樹, 佐竹 良之, 南場 研一, 深川 和己, 福島 敦樹, 藤島 浩, 高村 悦子 日本眼科學会雜誌 116 (5) 485 -493 2012年05月10日 [査読無し][通常論文]
  
• アレルギー性結膜疾患特異的 quality of life 調査票の確立

  深川 和己, 藤島 浩, 福島 敦樹, 角 環, 岡本 茂樹, 庄司 純, 佐竹 良之, 大野 重昭, 南場 研一, 北市 伸義, 海老原 伸行, 高橋 浩, 熊谷 直樹, 内野 裕一, 内野 美樹, 村山 公一, 坂田 実紀, 内尾 英一, 高村 悦子, 大橋 裕一, 大久保 公裕, 佐藤 敏彦 日本眼科學会雜誌 116 (5) 494 -502 2012年05月10日 [査読無し][通常論文]
  
• Behcet 病(ベーチェット病)眼病変診療ガイドライン

  大野 重昭, 蕪城 俊克, 北市 伸義, 後藤 浩, 南場 研一, 水木 信久, 飛鳥田 有里, 坂本 俊哉, 渋谷 悦子, 藤野 雄次郎, 目黒 明, 横井 克俊 日本眼科學会雜誌 116 (4) 394 -395 2012年04月10日 [査読無し][通常論文]
  
• S2-2 シクロスポリン点眼液の使用結果について(S2 (日本眼科アレルギー研究会)重症アレルギー性結膜疾患と免疫抑制剤点眼,シンポジウム2,第24回日本アレルギー学会春季臨床大会)

  南場 研一 アレルギー 61 (3) 390 -390 2012年04月10日 [査読無し][通常論文]
  
• 健康成人の片眼に発症した内因性真菌性眼内炎

  宇野 友絵, 南場 研一, 加瀬 諭, 齋藤 航, 北市 伸義, 大野 重昭, 石田 晋 あたらしい眼科 = Journal of the eye 29 (1) 135 -138 2012年01月30日 [査読無し][通常論文]
  
• 春季カタルに対するシクロスポリン点眼液0.1%の全例調査

  高村 悦子, 内尾 英一, 海老原 伸行, 岡本 茂樹, 熊谷 直樹, 庄司 純, 中川 やよい, 南場 研一, 福島 敦樹, 藤島 浩, 宮崎 大, 大橋 裕一 日本眼科學会雜誌 115 (6) 508 -515 2011年06月10日 [査読無し][通常論文]
  
• 口腔におけるカセリシジンファミリー抗菌ペプチドCAP18/LL37の微生物制御

  磯貝 浩, 磯貝 恵美子, 奥村 一彦, 南場 研一, 北市 伸義, 大野 重昭, 角舘 直樹 無菌生物 = Japanese journal of germfree life and gnotobiology 40 (2) 54 -59 2010年12月01日 [査読無し][通常論文]
  
• 炎症性眼疾患の診療(26)Behcet病

  南場 研一, 北市 伸義, 大野 重昭 臨床眼科 64 (5) 630 -636 2010年05月 [査読無し][通常論文]
  
• 内2 アレルギー性結膜疾患(教育講演,内科専門医コース2(眼科提供),第22回日本アレルギー学会春季臨床大会)

  大野 重昭, 北市 伸義, 南場 研一 アレルギー 59 (3) 261 -261 2010年04月10日 [査読無し][通常論文]
  
• 炎症性眼疾患の診療(25)真菌性眼内炎

  北市 伸義, 齋藤 航, 南場 研一 臨床眼科 64 (4) 416 -420 2010年04月 [査読無し][通常論文]
  
• Behcet 病に対するインフリキシマブ療法 : 生物学的製剤時代の幕開け

  南場 研一 日本眼科學会雜誌 114 (2) 85 -86 2010年02月10日 [査読無し][通常論文]
  
• ベーチェット病眼症状に対する顆粒球・単核球除去療法(<特集>血球成分除去療法の新しい展開)

  園田 康平, 南場 研一 日本アフェレシス学会雑誌 28 (1) 68 -71 2009年02月28日 [査読無し][通常論文]
   

  Intraocular inflammation (uveoretinitis) is one major complication of Behcet's disease (BD). We assess the efficacy of selective granulocytapheresis in patients with refractory uveoretinitis of BD. Fourteen patients were treated. Granulocytapheresis was done with an Adacolumn filled with cellulose acetate leucocyte carriers or beads that adsorb granulocytes and monocytes from the blood in the column. Each patient received 5 Adacolumn sessions at one session/week over 5 consecutive weeks. The study was designed to allow each patient to serve as his or her own control. The number of ocular at...
• 炎症性眼疾患の診療(21)HLA-B27関連ぶどう膜炎

  南場 研一, 北市 伸義, 三浦 淑恵 臨床眼科 62 (13) 1950 -1954 2008年12月 [査読無し][通常論文]
  
• ヒト白血球抗原(HLA)

  南場 研一 あたらしい眼科 = Journal of the eye 25 (11) 1479 -1483 2008年11月30日 [査読無し][通常論文]
  
• 臨床報告 春季カタルに対する0.1%シクロスポリン点眼液の臨床効果

  合田 千穂, 南場 研一, 北市 伸義 臨床眼科 62 (9) 1583 -1588 2008年09月 [査読無し][通常論文]
  
• PCR-SSOP-Luminex 法を用いた日本人 Behcet 病患者における症状別HLA-A, -B遺伝子解析

  上石 智子, 伊藤 良樹, 目黒 明, 西田 朋美, 佐々木 爽, 南場 研一, 大野 重昭, 猪子 英俊, 水木 信久 日本眼科學会雜誌 = Journal of Japanese Ophthalmological Society 112 (5) 451 -458 2008年05月10日 [査読無し][通常論文]
  
• 北海道大学における急性網膜壊死の臨床像

  水内 一臣, 南場 研一, 小竹 聡, 大野 重昭 日本眼科學会雜誌 = Journal of Japanese Ophthalmological Society 112 (2) 136 -140 2008年02月10日 [査読無し][通常論文]
  
• サルコイドーシス眼病変における重症, 難治性の検討

  飛鳥田 有里, 石原 麻美, 蓮見 由紀子, 中村 聡, 林 清文, 水木 信久, 南場 研一, 大野 重昭 日本眼科紀要 = Folia ophthalmologica Japonica 57 (12) 877 -880 2006年12月28日 [査読無し][通常論文]
  
• 生物学的製剤

  南場 研一, 大野 重昭 あたらしい眼科 = Journal of the eye 23 (11) 1409 -1414 2006年11月30日 [査読無し][通常論文]
  
• 顆粒球除去療法

  園田 康平, 南場 研一 あたらしい眼科 = Journal of the eye 23 (11) 1415 -1419 2006年11月30日 [査読無し][通常論文]
  
• Behcet 病眼症に対する顆粒球除去療法

  園田 康平, 南場 研一 眼科手術 = Journal of ophthalmic surgery 19 (4) 489 -491 2006年10月30日 [査読無し][通常論文]
  
• 広範な網脈絡膜萎縮を来した後部強膜炎の1例

  三浪 梨絵子, 齋藤 航, 南場 研一, 大野 重昭 日本眼科學会雜誌 = Journal of Japanese Ophthalmological Society 110 (9) 730 -735 2006年09月10日 [査読無し][通常論文]
  
• アレルギー性結膜疾患診療ガイドライン

  大野 重昭, 内尾 英一, 海老原 伸行, 大橋 裕一, 岡本 茂樹, 熊谷 直樹, 庄司 順, 高村 悦子, 中川 やよい, 南場 研一, 福島 敦樹, 藤島 浩 日本眼科學会雜誌 = Journal of Japanese Ophthalmological Society 110 (2) 99 -140 2006年02月10日 [査読無し][通常論文]
  
• 北海道大学大学院医学研究科 病態制御学専攻感覚器病学講座 視覚器病学分野 : ヌペ(涙)からミナミナ(微笑み)へ

  北明 大洲, 南場 研一 北海道醫學雜誌 = Acta medica Hokkaidonensia 81 (1) 85 -87 2006年01月01日 [査読無し][通常論文]
  
• カラー臨床報告 大量の線維素析出を伴うぶどう膜炎を発症した潰瘍性大腸炎の1例

  唐 尚子, 南場 研一, 村松 昌裕 臨床眼科 59 (9) 1609 -1612 2005年09月 [査読無し][通常論文]
  
• Current Review アレルギー性結膜疾患ガイドラインの話題

  南場 研一, 大野 重昭 Allergia trends 7 (3) 10 -13 2005年09月 [査読無し][通常論文]
  
• ぶどう膜炎併発白内障における手術適応の決定・術前後の処置

  南場 研一 あたらしい眼科 = Journal of the eye 21 (1) 3 -6 2004年01月30日 [査読無し][通常論文]