記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To evaluate 10-year outcome of infliximab (IFX) treatment for uveitis in Behçet disease (BD) patients using a standardized follow-up protocol. DESIGN: Retrospective longitudinal cohort study. PARTICIPANTS: 140 BD uveitis patients treated with IFX enrolled in our previous study. METHODS: Medical records were reviewed for demographic information, duration of IFX treatment, number of ocular attacks before IFX initiation, best corrected visual acuity (VA) at baseline and 1, 2, 3, 4, 5, and 10 years after IFX initiation, uveitis recurrence after IFX initiation and main anatomical site, concomitant therapies, and adverse events (AEs). MAIN OUTCOME MEASURES: 10-year IFX continuation rate and change in LogMAR VA. RESULTS: Of 140 BD patients, 106 (75.7%) continued IFX treatment for 10 years. LogMAR VA improved gradually after initiation of IFX, and the improvement reached statistical significance from 2 years of treatment. Thereafter, significant improvement compared with baseline was maintained until 10 years, despite a slight deterioration of logMAR VA from 5 years. However, eyes with worse baseline decimal VA < 0.1 showed no significant improvement from baseline to 10 years. Uveitis recurred after IFX initiation in 50 patients (recurrence group) and did not recur in 56 (non-recurrence group). Ocular attacks/year before IFX initiation was significantly higher in the recurrence group (2.82 ± 3.81) than in the non-recurrence group (1.84 ± 1.78). In the recurrence group, uveitis recurred within 1 year in 58% and within 2 years in 74%. Seventeen patients (34%) had recurrent anterior uveitis, 17 (34%) had posterior uveitis, and 16 (32%) had panuveitis, with no significant difference in VA outcome. In addition, logMAR VA at 10 years did not differ between the recurrence and non-recurrence groups. AEs occurred among 43 patients (30.7%), and 24 (17.1%) resulted in IFX discontinuation before 10 years. CONCLUSIONS: Among BD patients with uveitis who initiated IFX, approximately 75% continued treatment for 10 years, and their VA improved significantly and was maintained for 10 years. Uveitis recurred in one-half of the patients, but visual acuity did not differ significantly from the patients without recurrence.

DOI： 10.3389/fmed.2023.1095423

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

To reveal optimal antibiotic prophylactic regimen for postoperative endophthalmitis (POE), we conducted systematic review and network meta-analysis. A total of 51 eligible original articles, including two randomized controlled trials, were identified. In total, 4502 POE cases occurred in 6,809,732 eyes (0.066%). Intracameral injection of vancomycin had the best preventive effect (odds ratio [OR] 0.03, 99.6% confidence interval [CI] 0.00-0.53, corrected P-value = 0.006, P-score = 0.945) followed by intracameral injection of cefazoline (OR 0.09, 99.6% CI 0.02-0.42, corrected P-value < 0.001, P-score = 0.821), cefuroxime (OR 0.18, 99.6% CI 0.09-0.35, corrected P-value < 0.001, P-score = 0.660), and moxifloxacin (OR 0.36, 99.6% CI 0.16-0.79, corrected P-value = 0.003, P-score = 0.455). While one randomized controlled trial supported each of intracameral cefuroxime and moxifloxacin, no randomized controlled trial evaluated vancomycin and cefazoline. Sensitivity analysis focusing on the administration route revealed that only intracameral injection (OR 0.19, 99.4% CI 0.12-0.30, corrected P-value < 0.001, P-score = 0.726) significantly decreased the risk of postoperative endophthalmitis. In conclusion, intracameral injection of either vancomycin, cefazoline, cefuroxime, or moxifloxacin prevented POE.

DOI： 10.1038/s41598-022-21423-w

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To clarify the proportion of ocular sarcoidosis with severe, refractory, and prolonged inflammation and their association with ocular complications and visual prognosis. STUDY DESIGN: Multicenter, retrospective, longitudinal cohort study. METHODS: Three hundred and twenty-three eyes of 164 patients (45 men; 119 women) with ocular sarcoidosis who visited Hokkaido University Hospital and Yokohama City University Hospital from 2010 to 2015. We newly defined severe, refractory, and prolonged inflammation in ocular sarcoidosis, and investigated their proportions, ocular complications and final visual acuity from medical records of our sarcoidosis patients. RESULTS: The eyes with severe inflammation numbered 72/323 (22.3%), with refractory inflammation, 80/323 (24.8%), and with prolonged inflammation, 91/323 (28.2%). The number of eyes having neither severe, refractory, nor prolonged inflammation (defined as none) was 114/323 (35.3%). The numbers of eyes that reached irreversible visual dysfunction were 6/72 (8.3%) of those with severe inflammation, 10/80 (12.5%) with refractory inflammation, 12/91 (13.2%) with prolonged inflammation, and 4/114 (6.2%) with none. As complications, cataract (62.2%), glaucoma (28.5%), epiretinal membrane (24.1%), cystoid macular edema (22.6%), vitreous hemorrhage (2.8%), choroidal atrophy (2.5%), macular degeneration (1.2%), macular hole (0.9%) and retinal detachment (0.3%) were identified. Among them, secondary glaucoma (16 eyes) and macular degeneration (4 eyes) were major complications related to irreversible visual dysfunction. CONCLUSIONS: Although most of the patients with ocular sarcoidosis had a relatively good visual prognosis, some developed severe, refractory, and/or prolonged inflammation related to the development of ocular complications, that resulted in poor visual prognosis.

DOI： 10.1007/s10384-022-00927-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The induction of T cell-mediated immunity is crucial in vaccine development. The most effective vaccine is likely to employ both cellular and humoral immune responses. The efficacy of a vaccine depends on T cells activated by antigen-presenting cells. T cells also play a critical role in the duration and cross-reactivity of vaccines. Moreover, pre-existing T-cell immunity is associated with a decreased severity of infectious diseases. Many technical and delivery platforms have been designed to induce T cell-mediated vaccine immunity. The immunogenicity of vaccines is enhanced by controlling the kinetics and targeted delivery. Viral vectors are attractive tools that enable the intracellular expression of foreign antigens and induce robust immunity. However, it is necessary to select an appropriate viral vector considering the existing anti-vector immunity that impairs vaccine efficacy. mRNA vaccines have the advantage of rapid and low-cost manufacturing and have been approved for clinical use as COVID-19 vaccines for the first time. mRNA modification and nanomaterial encapsulation can help address mRNA instability and translation efficacy. This review summarizes the T cell responses of vaccines against various infectious diseases based on vaccine technologies and delivery platforms and discusses the future directions of these cutting-edge platforms.

DOI： 10.3390/vaccines10081367

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記述言語：日本語   出版者・発行元：(公社)神奈川県医師会  

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記述言語：日本語   出版者・発行元：(公社)神奈川県医師会  

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記述言語：日本語   出版者・発行元：(公社)神奈川県医師会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: We investigated efficacy and safety of adalimumab (ADA) treatment for exacerbation or recurrence of Vogt-Koyanagi-Harada (VKH) patients. METHODS: Medical records of 70 VKH patients who received ADA treatment for more than 6 months were retrospectively investigated. RESULTS: The mean age of VKH patients was 54.8 ± 15.1 years, and male/female ratio was 34/36, and sunset glow fundus was observed in 71.4%. Subfoveal choroidal thickness, indocyanine green angiography scores, and corticosteroid and cyclosporine doses were significantly reduced by ADA treatment for 6 months compared to baseline, while LogMAR and flare counts were also improved without being statistically significant. Adverse events were observed in 17.1%, in which tuberculosis was at 7.14% and psoriasis was at 2.86%; however, ADA treatment was continued in 91.4%. CONCLUSIONS: ADA was shown to be effective to achieve remission of VKH disease refractory to conventional treatments and was generally well tolerated with few serious adverse events.

DOI： 10.1080/09273948.2022.2092007

PubMed

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記述言語：日本語   出版者・発行元：(株)医学書院  

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記述言語：日本語   出版者・発行元：(株)医学書院  

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記述言語：日本語   出版者・発行元：(公社)日本皮膚科学会  

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記述言語：日本語   出版者・発行元：(株)メディカル葵出版  

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記述言語：日本語   出版者・発行元：(株)医学書院  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2022&ichushi_jid=J01537&link_issn=&doc_id=20220405150022&doc_link_id=10.11477%2Fmf.1410214358&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1410214358&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To compare the efficacy and safety of a combination therapy of prednisolone and cyclosporine and corticosteroid pulse therapy in Vogt-Koyanagi-Harada (VKH) disease. STUDY DESIGN: A prospective, multicenter, randomized, non-inferiority trial. METHODS: Patients of new-onset acute VKH disease at 11 centers in Japan between 2014 and 2018 were randomized to a combination (oral prednisolone 60 mg daily with gradual taper-off to 35 mg/day and cyclosporine 3 mg/kg/day) and corticosteroid (methylprednisolone 1000 mg for 3 days followed by oral prednisolone) groups, and were followed for 1 year. RESULTS: Thirty-four were assigned to the combination and thirty-six patients to the corticosteroid group. Recurrence/worsening risk was 0.15 (95% confidence-interval [CI] 0.03-0.27) in the combination group and 0.25 (95% CI 0.11-0.39) in the corticosteroid group, with a risk difference of - 0.10 (90% CI - 0.27 to 0.06), demonstrating non-inferiority of the combination group with a non-inferiority margin of 0.20 (P = 0.0013). Serious adverse events occurred in three patients (two with hyponatremia and one with severe headaches) in the combination group and none in the corticosteroid group. Sunset glow fundus grades and cataract rates at 1 year were 0.57 (95% CI 0.42-71) and 4.3% in the combination group and 0.91 (95% CI 0.78-1.04) and 34.0% in the corticosteroid group, respectively. CONCLUSIONS: Combination therapy was noninferior to corticosteroid therapy with respect to recurrence/worsening risk. Notably, the recurrence/worsening risk, sunset glow fundus grade, and cataract rate were lower in the combination group than in the corticosteroid group.

DOI： 10.1007/s10384-021-00878-w

PubMed

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Refractive changes are reportedly affected by age, sex, and current refractive error. To clarify the pattern of refractive changes in a Japanese population, we conducted a 5-year follow-up longitudinal analysis of spherical equivalent (SE) refractive changes with stratification by sex, age, and SE in 593,273 eyes from Japanese individuals ages 3-91 years. The 5-year SE change with myopic shift dramatically increased over time after age 4 years, and the largest change was observed in both males and females who were age 8 years at baseline [males: - 2.654 ± 0.048 diopters (D); females: - 3.110 ± 0.038 D]. During school age, the 5-year myopic change was greater in females than in males, and emmetropic and low-to-moderate myopic eyes underwent larger myopic changes than hyperopic and high-to-severe myopic eyes. After the peak at age 8 years, the 5-year myopic change gradually declined with age and fell below - 0.25 D at age 27 in males and age 26 years in females. The 5-year SE changes transitioned from a myopic to a hyperopic shift at age 51 in both sexes, and hyperopization advanced more quickly in hyperopic eyes. Our findings highlight the importance of myopia prevention in school-aged children.

DOI： 10.1038/s41598-022-06898-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: To investigate the causes of low prevalence of Fuchs' uveitis syndrome (FUS) in Japan. METHODS: Medical records of 160 patients diagnosed with FUS at 14 uveitis specialty facilities in Japan were reviewed retrospectively. RESULTS: In 160 FUS patients, mean follow-up period before referral to our uveitis facilities was 31.6 ± 50.9 months. The most common reason for referral was idiopathic uveitis (61.9%), followed by cataract (25.0%), high intraocular pressure (IOP) including glaucoma (16.3%), and FUS (14.4%). Unilateral involvement was 96.9%. The most frequent ocular finding of FUS was anterior inflammation (91.9%), followed by stellate-shaped keratic precipitates (88.1%), cataract/pseudophakia (88.1%), diffuse iris atrophy (84.4%), vitreous opacity (62.5%), heterochromia (53.1%) and high IOP including glaucoma (36.3%). As treatments of these ocular findings, cataract surgery was performed in 52.5%, glaucoma surgery in 10.6%, and vitrectomy in 13.8%. Mean logMAR VA was 0.28 ± 0.59 at the initial visit, and decreased significantly to 0.04 ± 0.32 at the last visit. Proportions of FUS patients with BCVA <0.1 and 0.1 to <0.5 decreased, while that of ≥0.5 increased at the last visit compared with the initial visit. CONCLUSIONS: Ocular findings of FUS in Japanese FUS patients were consistent with the characteristic features. The low prevalence of FUS in Japan may be a result of being overlooked and misdiagnosed as mild idiopathic uveitis, cataract, and/or glaucoma.

DOI： 10.3389/fmed.2022.999804

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: We investigated the efficacy and safety of adalimumab (ADA) treatment for chronic recurrent Vogt-Koyanagi-Harada (VKH) patients with sunset glow fundus (SGF). METHODS: Medical records of 50 chronic recurrent VKH patients with SGF who received ADA treatment for more than 6 months were retrospectively reviewed. RESULTS: The mean age of chronic recurrent VKH patients with SGF was 55.9 ± 14.4 years, and the male/female ratio was 26/24. Before ADA treatment, the mean daily dose of systemic corticosteroids was 16.5 ± 12.7 mg, and 22 patients (44%) were under immunosuppressors. LogMAR visual acuity (VA), flare counts, subfoveal choroidal thickness (SFCT), indocyanine green angiography scores, and corticosteroid and cyclosporine doses were significantly reduced by ADA treatment at 6 months compared to baseline. Among all parameters, flare count was significantly related to LogMAR VA. LogMAR VA was significantly related to flare counts but not to SFCT nor to ICGA scores. ADA treatment was continued in 94%. CONCLUSION: ADA was shown to be effective in achieving remission of chronic recurrent VKH disease with SGF refractory to conventional treatments, and was generally well tolerated with few serious adverse events.

DOI： 10.4103/sjopt.sjopt_204_22

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Immune tolerance is established in the eye to prevent permanent blindness associated with destructive damage to the cornea and retina caused by immune cell infiltration; hence, the immune responses and subsequent inflammations are strongly suppressed. While non-infectious uveitis develops from a disruption of immune tolerance in the eye, its onset is a result of accumulating etiologic factors, including genetic predisposition, environmental factors, and aging. Many non-infectious uveitis cases are genetically predisposed to human leukocyte antigen (HLA) as the most substantial disease susceptibility region. HLA class I molecules are critical for natural killer (NK) cells to distinguish between self and non-self. The killer cell Ig-like receptor (KIR) family is one of the essential components of these receptors. Evidence has accumulated that NK cells are involved in innate and acquired immunity by interacting with other immunocompetent cells to develop several autoimmune diseases. This review summarizes the possible role of KIR in the development of non-infectious uveitis.

DOI： 10.2174/1566524021666211027092124

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

DOI： 10.1007/s40123-021-00390-x

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

DOI： 10.1007/s40123-021-00368-9

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

<title>Abstract</title><sec>
<title>Background</title>
We hypothesized that Behçet’s disease (BD) consists of several clinical subtypes with different severity, resulting in heterogeneity of the disease. Here, we conducted a study to identify clinical clusters of BD.


</sec><sec>
<title>Methods</title>
A total of 657 patients registered in the Yokohama City University (YCU) regional BD registry between 1990 and 2018, as well as 6754 patients who were initially registered in the Japanese Ministry of Health, Labour and Welfare (MHLW) database between 2003 and 2014, were investigated. The YCU registry data regarding the clinical manifestations of BD, human leukocyte antigen (HLA) status, treatments, and hospitalizations were analyzed first, followed by similar analyses of the MHLW for validation. A hierarchical cluster analysis was independently performed in both patient groups.


</sec><sec>
<title>Results</title>
A hierarchical cluster analysis determined five independent clinical clusters in the YCU cohort. Individual counterparts of the YCU clusters were confirmed in the MHLW registry. Recent phenotypical evolutions of BD in Japan, such as increased gastrointestinal (GI) involvement, reduced complete type according to the Japan Criteria, and reduced HLA-B51 positivity were associated with chronologically changing proportions of the clinical clusters.


</sec><sec>
<title>Conclusions</title>
In this study, we identified independent clinical clusters among BD patients in Japan and found that the proportion of each cluster varied over time. We propose five independent clusters namely “mucocutaneous”, “mucocutaneous with arthritis”, “neuro”, “GI”, and “eye.”


</sec>

DOI： 10.1186/s13075-020-02406-6

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その他リンク： http://link.springer.com/article/10.1186/s13075-020-02406-6/fulltext.html

記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: This study aimed to determine the clinical efficacy of apremilast for oral ulcers, extra-oral manifestations, and overall disease activity in patients with Behçet's disease (BD). METHODS: A systematic literature search was performed in PubMed, EMBASE, Cochrane Library, and Web of Science Core Collection. Studies assessing the treatment effects of apremilast in BD were included. The odds ratios (ORs) of being symptom free for individual manifestations and mean difference (MD) of Behçet's Disease Current Activity Form (BDCAF) scores were calculated with 95% confidence intervals (CIs) at 12 and 24 weeks using a random-model meta-analysis. RESULTS: Of 259 screened articles, eight were included. After 12 weeks of apremilast treatment the OR of symptom-free was as followings: oral ulcers, 45.76 (95% CI, 13.23-158.31); genital ulcers, 4.56 (95% CI, 2.47-8.44); erythema nodosum, 3.59 (95% CI, 1.11-11.61); pseudofolliculitis, 2.81 (95% CI, 1.29-6.15); and arthritis, 3.55 (95% CI, 1.71-7.40). Furthermore, BDCAF scores at 12 weeks were significantly reduced (MD=-1.38; -1.78 to -0.99). However, the proportion of oral-ulcer free patients increased at 24 weeks (OR=14.88; 4.81 to 46.07). CONCLUSION: The currently accumulated data indicates an improvement in mucocutaneous and articular symptoms by short-term apremilast treatment in patients with BD.

DOI： 10.1093/mr/roab098

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

DOI： 10.1016/j.bjps.2021.03.086

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Although infliximab (IFX) decreases the risk of blindness due to refractory uveitis in patients with Behçet's disease (BD), there are no standard criteria for IFX switching or withdrawal. To evaluate the effect of IFX switching in patients with BD in long-term remission, a prospective, single-arm intervention trial was conducted, switching from IFX to cyclosporine A (CYA). STUDY DESIGN: A prospective open-label study. METHODS: Eligible patients met the following criteria: administration of IFX without concomitant immunosuppressants for more than 5 years with no episodes of ocular attacks, no retinal vasculitis on fluorescein fundus angiography, negative C-reactive protein in serum, and no extraocular lesions at the time of IFX withdrawal. CYA 5 mg/kg/day was administered from 6 weeks after IFX withdrawal. The primary outcome was the rate of readministration of tumor necrosis factor inhibitors at 1 year after IFX withdrawal. RESULTS: Three of 45 BD patients treated with IFX for refractory uveitis were included in the study. At 1 year after withdrawal of IFX, no patient had experienced any ocular attacks or needed readministation of IFX. However, extraocular lesions, such as recurrent oral ulcers, folliculitis, and recurrent fevers, occurred in all patients. Liver or renal dysfunction, which may have been caused by CYA, was also observed in all patients. CONCLUSIONS: Although no ocular attacks were observed for at least 1 year after IFX withdrawal, this prospective study indicates that IFX withdrawal should be considered carefully, even for patients in long term remission of ocular and extraocular lesions.

DOI： 10.1007/s10384-021-00872-2

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記述言語：日本語   出版者・発行元：(公社)日本眼科手術学会  

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記述言語：日本語   出版者・発行元：(公社)神奈川県医師会  

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記述言語：日本語   出版者・発行元：(公社)神奈川県医師会  

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記述言語：日本語   出版者・発行元：(公社)神奈川県医師会  

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記述言語：日本語   出版者・発行元：(株)日本医事新報社  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J01024&link_issn=&doc_id=20210701010007&doc_link_id=%2Faf9mdcla%2F2021%2F005071%2F009%2F0028b0032%26dl%3D3&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faf9mdcla%2F2021%2F005071%2F009%2F0028b0032%26dl%3D3&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_4.gif

記述言語：日本語   出版者・発行元：(公社)神奈川県医師会  

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Oxford University Press (OUP)  

<title>Abstract</title>
<sec>
<title>Objectives</title>
No large-scale registration study has comprehensively evaluated the activities of daily living (ADL) in patients with Behçet's disease (BD).


</sec>
<sec>
<title>Methods</title>
The Japanese government provided us with a dataset of confirmed or suspected BD cases derived from ongoing national registration. ADL were categorized and analyzed into four categories in patients who satisfied the international criteria for BD.


</sec>
<sec>
<title>Results</title>
Data from 2960 patients (men, 38.9%; women, 61.1%; median age 39 years) were assessed. While 1767 patients (59.7%) had normal ADL, the others had impaired ADL comprising: limited but not assisted, 1058 (35.7%); partially assisted, 116 (3.9%); and fully assisted, 19 (0.6%). Logistic regression analysis showed that chronic ocular lesions (odds ratio (OR) 1.85, 95% confidence interval (CI) 1.46–2.35, p&amp;lt; 0.001), paralysis (OR 2.51, 95% CI 1.58–3.97, p&amp;lt; 0.001), psychosis (OR 3.16, 95% CI 2.02–4.95, p&amp;lt; 0.001), and arthritis (OR 1.69, 95% CI 1.44–1.99, p&amp;lt; 0.001) led to the risk of impaired ADL (not normal ADL). Chronic ocular lesions (OR 3.61, 95% CI 2.27–5.72, p&amp;lt; 0.001), paralysis (OR 3.43, 95% CI 1.87–6.30, p&amp;lt; 0.001), and psychosis (OR 3.60, 95% CI 2.00–6.50, p&amp;lt; 0.001) were related to the requirement of physical assistance (partially or fully assisted), although arthritis (OR 1.39, 95% CI 0.93–2.06, p= 0.108) was not a significant factor in this model.


</sec>
<sec>
<title>Conclusion</title>
Ocular lesion, neurological manifestations, and arthritis affected ADL. Patients with ocular lesion or neurological manifestations more frequently required physical assistance.


</sec>

DOI： 10.1093/rheumatology/keab499

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Adenovirus infections are a major cause of epidemic keratoconjunctivitis (EKC), which can lead to corneal subepithelial infiltrates and multifocal corneal opacity. In the current study, we investigated the use of an E1/E3-deleted adenovirus serotype 5 (Ad5) vector as a vaccine administered intramuscularly (IM) or intranasally (IN) against subsequent challenges with a luciferase-expressing Ad5 (Ad5-Luci) vector via eyedrop. We evaluated the adaptive immune response to Ad5 vector vaccination and confirmed a robust polyfunctional CD8 T cell response in splenic cells. Neutralizing Ad5 antibodies were also measured in the sera of vaccinated mice as well as Ad5 antibody in the eye wash solutions. Upon challenge with Ad5-Luci vector 8 weeks post the primary immunization, transduction was significantly reduced by > 70% in the vaccinated mice, which was slightly better in IM- vs. that in IN-vaccinated animals. Resistance to subsequent challenge was observed 10 months post primary IM vaccination, with sustained reduction up to 60% in the Ad5-Luci vector transduction. Passive immunization of naive mice with antisera from IM to vaccinated mice subsequently challenged with the Ad5-Luci vector resulted in approximately 40% loss in transduction efficiency. Furthermore, the mice that received IM immunization with or without CD8 T cell depletion showed > 40% and 70% reductions, respectively, in Ad8 genomic copies after Ad8 topical challenge. We conclude that Ad-vector vaccination successfully induced an adaptive immune response that prevented subsequent Ad transduction in the cornea and conjunctiva-associated tissues in a mouse model of adenovirus keratoconjunctivitis, and that both cellular and humoral immunity play an important role in preventing Ad transduction.

DOI： 10.1016/j.vaccine.2021.05.010

PubMed

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記述言語：日本語   出版者・発行元：(株)日本臨床社  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J01205&link_issn=&doc_id=20210603150002&doc_link_id=%2Fag6niria%2F2021%2F007906%2F002%2F0800-0804%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fag6niria%2F2021%2F007906%2F002%2F0800-0804%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(株)日本臨床社  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Pseudomonas aeruginosa (P. aeruginosa) infection is one of the major causes of keratitis. However, effective prophylactic and therapeutic vaccines against P. aeruginosa keratitis have yet to be developed. In this study, we explored the use of P. aeruginosa membrane vesicles (MVs) as a prophylactic vaccine as well as the use of immune sera derived from P. aeruginosa MV-immunized animals as a treatment for P. aeruginosa corneal infections in C57BL/6 mice. METHODS: C57BL/6 mice were intramuscularly immunized with P. aeruginosa MVs; the mouse corneas were then scarified and topically infected with several P. aeruginosa strains, followed by determination of corneal clinical score and corneal bacterial load. Next, immune sera derived from P. aeruginosa MV-immunized ICR mice were administered intraperitoneally to naïve C57BL/6 mice, followed by topical P. aeruginosa challenge. Finally, the immune sera were also used as a topical treatment in the mice with established P. aeruginosa corneal infections. RESULTS: P. aeruginosa-specific IgG and IgA antibodies induced by intramuscular immunization were detected not only in the sera but also in the eye-wash solution. Both active and passive immunization significantly inhibited P. aeruginosa corneal infection. Finally, topical treatment with immune sera in the mice with established P. aeruginosa corneal infections notably decreased the corneal clinical score and corneal bacterial load. CONCLUSIONS: P. aeruginosa keratitis can be attenuated by vaccination of P. aeruginosa MVs and topical application of P. aeruginosa MV-specific immune sera.

DOI： 10.1016/j.vaccine.2021.04.035

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Guidelines and systematic reviews frequently warn of inhaled corticosteroid (ICS)-induced glaucoma. However, most of the published studies deny it. METHODS: We performed a systematic review of randomized, cohort, nested-case control, cross-sectional studies by using Meta-analyses of Observational Studies in Epidemiology statement. Four major databases, PubMed, EMBASE, Cochrane Search Manager, and the Web of Science Core Collection as well as meta-analysis were used. Studies comparing incidence, prevalence and intraocular pressure (IOP) between patients who were treated with and without ICSs were included. A random-model meta-analysis was performed using the inverse variance method. RESULTS: Out of 623 studies screened, 18 with 31,665 subjects were finally included. No significant difference between the 2 groups was observed for crude glaucoma incidence (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.86-1.04; P = 0.26; I² = 0%; P for heterogeneity = 0.57) as a primary endpoint, adjusted glaucoma incidence (OR, 0.90; 95% CI, 0.65-1.24; P = 0.64), crude prevalence (OR, 1.82; 95% CI, 0.23-14.19; P = 0.57), adjusted prevalence (OR, 1.22; 95% CI, 0.50-2.96; P = 0.66), IOP change during ICS treatment (mean difference [MD] +0.01 mmHg; 95% CI, -0.19-0.20; P = 0.95), and single measurement IOP (MD +0.37 mmHg; 95% CI, -0.24-0.97; P = 0.23). Time-to-event analysis for glaucoma development as one of the secondary endpoints (adjusted hazard ratio, 0.52; 95% CI, 0.28-0.96) suggested a reverse association between ICS and glaucoma. CONCLUSIONS: The ophthalmological side effects of ICSs, such as glaucoma and intraocular hypertension, should not be exaggerated. TRIAL REGISTRATION: University Hospital Medical Information Network Center Clinical Trial Registry Identifier: UMIN000040351.

DOI： 10.4168/aair.2021.13.3.435

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J01049&link_issn=&doc_id=20210419580003&doc_link_id=%2Fdz1nigan%2F2021%2F012504%2F002%2F0415-0424%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdz1nigan%2F2021%2F012504%2F002%2F0415-0424%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The threat of the current coronavirus disease pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is accelerating the development of potential vaccines. Candidate vaccines have been generated using existing technologies that have been applied for developing vaccines against other infectious diseases. Two new types of platforms, mRNA- and viral vector-based vaccines, have been gaining attention owing to the rapid advancement in their methodologies. In clinical trials, setting appropriate immunological endpoints plays a key role in evaluating the efficacy and safety of candidate vaccines. Updated information about immunological features from individuals who have or have not been exposed to SARS-CoV-2 continues to guide effective vaccine development strategies. This review highlights key strategies for generating candidate SARS-CoV-2 vaccines and considerations for vaccine development and clinical trials.

DOI： 10.1016/j.vaccine.2020.11.054

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記述言語：日本語   出版者・発行元：(株)医学書院  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J01537&link_issn=&doc_id=20210108070008&doc_link_id=10.11477%2Fmf.1410213875&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1410213875&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Dove Medical Press Ltd  

DOI： 10.2147/OPTH.S327660

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Uveitis is a generic term for inflammation of the uvea, which includes the iris, ciliary body, and choroid. Prevalence of underlying non-infectious uveitis varies by race and region and is a major cause of legal blindness in developed countries. Although the etiology remains unclear, the involvement of both genetic and environmental factors is considered important for the onset of many forms of non-infectious uveitis. Major histocompatibility complex (MHC) genes, which play a major role in human immune response, have been reported to be strongly associated as genetic risk factors in several forms of non-infectious uveitis. Behçet's disease, acute anterior uveitis (AAU), and chorioretinopathy are strongly correlated with MHC class I-specific alleles. Moreover, sarcoidosis and Vogt-Koyanagi-Harada (VKH) disease are associated with MHC class II-specific alleles. These correlations can help immunogenetically classify the immune pathway involved in each form of non-infectious uveitis. Genetic studies, including recent genome-wide association studies, have identified several susceptibility genes apart from those in the MHC region. These genetic findings help define the common or specific pathogenesis of ocular inflammatory diseases by comparing the susceptibility genes of each form of non-infectious uveitis. Interestingly, genome-wide association of the interleukin (IL)23R region has been identified in many of the major forms of non-infectious uveitis, such as Behçet's disease, ocular sarcoidosis, VKH disease, and AAU. The interleukin-23 (IL-23) receptor, encoded by IL23R, is expressed on the cell surface of Th17 cells. IL-23 is involved in the homeostasis of Th17 cells and the production of IL-17, which is an inflammatory cytokine, indicating that a Th17 immune response is a common key in the pathogenesis of non-infectious uveitis. Based on the findings from the immunogenetics of non-infectious uveitis, a personalized treatment approach based on the patient's genetic make-up is expected.

DOI： 10.3389/fimmu.2021.640473

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

DOI： 10.1038/s42003-020-0802-y

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記述言語：日本語   出版者・発行元：(株)医学書院  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01537&link_issn=&doc_id=20201202100022&doc_link_id=10.11477%2Fmf.1410213860&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1410213860&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

掲載種別：研究論文（学術雑誌）   出版者・発行元：Informa UK Limited  

DOI： 10.1080/14397595.2020.1830504

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose: To identify the clinical characteristics of acute retinal necrosis (ARN) and clarify factors associated with poor visual prognosis. Methods: a nationwide multi-center retrospective chart review study was performed in Japan using data from the medical records of 149 consecutive ARN patients. Demographics, ocular signs, virologic testing of intraocular fluids, and treatment were examined. Factors associated with poor visual prognosis were investigated by regression analysis. Results: At initial presentation, anterior chamber cells or mutton-fat keratic precipitates (97%), unilaterality (93%), and yellow-white retinal lesions (86%) were recognized. In the clinical course, rapid circumferential expansion of retinal lesions (39%), development of retinal break or retinal detachment (55%), and optic atrophy (43%) were recorded. Four variables were identified as associated with poor visual prognosis. Conclusions: The present study identified clinical characteristics and factors associated with poor visual prognosis of ARN.

DOI： 10.1080/09273948.2020.1789179

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Lippincott Williams and Wilkins  

DOI： 10.1097/APO.0000000000000310

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記述言語：日本語   出版者・発行元：(株)医学書院  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Oncoprotein E6 of high-risk human papillomavirus (HPV) plays a critical role in inducing cell immortalization and malignancy. E6 downregulates caspase-dependent pathway through the degradation of p53. However, the effect of HPV E6 on other pathways is still under investigation. In the present study, we found that HPV E6 directly binds to all three forms (precursor, mature, and apoptotic) of apoptosis-inducing factor (AIF) and co-localizes with apoptotic AIF. This binding induced MG132-sensitive reduction of AIF expression in the presence of E6 derived from HPV16 (16E6), a cancer-causing type of HPV. Conversely, E6 derived from a non-cancer-causing type of HPV, HPV6 (6E6), did not reduce the levels of AIF despite its interaction with AIF. Flow cytometric analysis revealed that 16E6, but not 6E6, suppressed apoptotic AIF-induced chromatin degradation (an indicator of caspase-independent apoptosis) and staurosporine (STS, a protein kinase inhibitor)-induced apoptosis. AIF knockdown reduced STS-induced apoptosis in both of 16E6-expressing and 6E6-expressing cells; however, the reduction in 16E6-expressing cells was lower than that in 6E6-expressing cells. These findings indicate that 16E6, but not 6E6, blocks AIF-mediated apoptosis, and that AIF may represent a novel therapeutic target for HPV-induced cervical cancer.

DOI： 10.1038/s41598-020-71134-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Sarcoidosis is a genetically complex systemic inflammatory disease that affects multiple organs. We present a GWAS of a Japanese cohort (700 sarcoidosis cases and 886 controls) with replication in independent samples from Japan (931 cases and 1,042 controls) and the Czech Republic (265 cases and 264 controls). We identified three loci outside the HLA complex, CCL24, STYXL1-SRRM3, and C1orf141-IL23R, which showed genome-wide significant associations (P < 5.0 × 10-8) with sarcoidosis; CCL24 and STYXL1-SRRM3 were novel. The disease-risk alleles in CCL24 and IL23R were associated with reduced CCL24 and IL23R expression, respectively. The disease-risk allele in STYXL1-SRRM3 was associated with elevated POR expression. These results suggest that genetic control of CCL24, POR, and IL23R expression contribute to the pathogenesis of sarcoidosis. We speculate that the CCL24 risk allele might be involved in a polarized Th1 response in sarcoidosis, and that POR and IL23R risk alleles may lead to diminished host defense against sarcoidosis pathogens.

DOI： 10.1038/s42003-020-01185-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Keratoconus is a common ocular disorder that causes progressive corneal thinning and is the leading indication for corneal transplantation. Central corneal thickness (CCT) is a highly heritable characteristic that is associated with keratoconus. In this two-stage genome-wide association study (GWAS) of CCT, we identified a locus for CCT, namely STON2 rs2371597 (P = 2.32 × 10-13), and confirmed a significant association between STON2 rs2371597 and keratoconus development (P = 0.041). Additionally, strong STON2 expression was observed in mouse corneal epithelial basal cells. We also identified SMAD3 rs12913547 as a susceptibility locus for keratoconus development using predictive analysis with IBM's Watson question answering computer system (P = 0.001). Further GWAS analyses combined with Watson could effectively reveal detailed pathways underlying keratoconus development.

DOI： 10.1038/s42003-020-01137-3

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

DOI： 10.1186/s12886-020-01571-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Behçet's disease (BD) is an intractable systemic inflammatory disease characterized by four main symptoms: oral and genital ulcers and ocular and cutaneous involvement. The Japanese diagnostic criteria of BD classify intestinal BD as a specific disease type. Volcano-shaped ulcers in the ileocecum are a typical finding of intestinal BD, and punched-out ulcers can be observed in the intestine or esophagus. Tumor necrosis factor inhibitors were first approved for the treatment of intestinal BD in Japan and have been used as standard therapy. In 2007 and 2014, the Japan consensus statement for the diagnosis and management of intestinal BD was established. Recently, evidence-based JSBD (Japanese Society for BD) Clinical Practice Guidelines for BD (Japanese edition) were published, and the section on intestinal BD was planned to be published in English. Twenty-eight important clinical questions (CQs) for diagnosis (CQs 1-6), prognosis (CQ 7), monitoring and treatment goals (CQs 8-11), medical management and general statement (CQs 12-13), medical treatment (CQs 14-22), and surgical treatment (CQs 23-25) of BD and some specific situations (CQs 26-28) were selected as unified consensus by the members of committee. The statements and comments were made following a search of published scientific evidence. Subsequently, the levels of recommendation were evaluated based on clinical practice guidelines in the Medical Information Network Distribution Service. The degree of agreement was calculated using anonymous voting. We also determined algorithms for diagnostic and therapeutic approaches for intestinal BD. The present guidelines will facilitate decision making in clinical practice.

DOI： 10.1007/s00535-020-01690-y

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記述言語：日本語   出版者・発行元：(株)医学書院  

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記述言語：日本語   出版者・発行元：金原出版(株)  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J00293&link_issn=&doc_id=20200629080003&doc_link_id=10.18888%2Fga.0000001692&url=https%3A%2F%2Fdoi.org%2F10.18888%2Fga.0000001692&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To identify novel susceptibility loci for high myopia. DESIGN: Genome-wide association study (GWAS) followed by replication and meta-analysis. PARTICIPANTS: A total of 14 096 samples from East and Southeast Asian populations (2549 patients with high myopia and 11 547 healthy controls). METHODS: We performed a GWAS in 3269 Japanese individuals (1668 with high myopia and 1601 control participants), followed by replication analysis in a total of 10 827 additional samples (881 with high myopia and 9946 control participants) from Japan, Singapore, and Taiwan. To confirm the biological role of the identified loci in the pathogenesis of high myopia, we performed functional annotation and Gene Ontology (GO) analyses. MAIN OUTCOME MEASURES: We evaluated the association of single nucleotide polymorphisms with high myopia and GO terms enriched among genes identified in the current study. RESULTS: We identified 9 loci with genome-wide significance (P < 5.0 × 10-8). Three loci were previously reported myopia-related loci (ZC3H11B on 1q41, GJD2 on 15q14, and RASGRF1 on 15q25.1), and the other 6 were novel (HIVEP3 on 1p34.2, NFASC/CNTN2 on 1q32.1, CNTN4/CNTN6 on 3p26.3, FRMD4B on 3p14.1, LINC02418 on 12q24.33, and AKAP13 on 15q25.3). The GO analysis revealed a significant role of the nervous system related to synaptic signaling, neuronal development, and Ras/Rho signaling in the pathogenesis of high myopia. CONCLUSIONS: The current study identified 6 novel loci associated with high myopia and demonstrated an important role of the nervous system in the disease pathogenesis. Our findings give new insight into the genetic factors underlying myopia, including high myopia, by connecting previous findings and allowing for a clarified interpretation of the cause and pathophysiologic features of myopia at the molecular level.

DOI： 10.1016/j.ophtha.2020.05.014

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記述言語：日本語   出版者・発行元：(株)メディカルレビュー社  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01750&link_issn=&doc_id=20200512150014&doc_link_id=%2Fai1phmdl%2F2020%2F003804%2F013%2F0061-0066%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fai1phmdl%2F2020%2F003804%2F013%2F0061-0066%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: To evaluate the efficacy of a mydriatic agent for posterior synechiae after phacoemulsification and intraocular lens (IOL) implantation followed by Descemet membrane endothelial keratoplasty (staged DMEK). METHODS: In this prospective study, the outcomes of DMEK with or without mydriasis (0.5% tropicamide and 0.5% phenylephrine hydrochloride [Mydrin-P; Santen, Osaka, Japan]) after the DMEK procedure were analyzed. Patients underwent IOL implantation approximately 4 weeks before DMEK. Six months after DMEK, the iris posterior synechiae severity score was evaluated based on the extent of posterior synechiae affecting the eight areas (45° each) of the pupillary rim (posterior synechiae score; grades 0-8). Best spectacle-corrected visual acuity, central corneal thickness, endothelial cell density, axial length, and the amount of air at the end of the surgery were also evaluated. RESULTS: Fifteen eyes of 15 patients (mydriatic: n=8, control: n=7) were eligible for inclusion. Iris posterior synechiae were detected in all seven eyes (100.0%) in the control group, whereas they were noted in two eyes in the mydriatic group (25%). The mean iris posterior synechiae score was 0.69±1.20 in the mydriatic group and was significantly lower than that in the control group (4.57±0.90; P<0.001). There was no significant difference in other clinical factors. Although the incidence and scores of posterior synechiae in the control group were higher, the incidence was significantly reduced with the use of a mydriatic agent (in the mydriatic group). CONCLUSIONS: Use of a mydriatic agent is an effective measure to prevent postoperative synechiae after DMEK.

DOI： 10.1097/ICL.0000000000000616

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記述言語：日本語   出版者・発行元：(公財)日本眼科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

In the current study, we present guidelines for the diagnosis and treatment of the mucocutaneous lesions of Behçet's disease, which is a chronic inflammatory disease characterized by the involvement of various organs, including mucocutaneous, ocular, vascular, intestinal and central nervous system lesions. It is often identified in the Middle East Mediterranean to East Asia region. Skin manifestations include erythema nodosum, papulopustular lesions and thrombophlebitis, and mucosal manifestations include oral and genital ulcers. These mucocutaneous lesions are characteristically the first signs of Behçet's disease and are important to be recognized for the early diagnosis of the disease. Moreover, these manifestations also recur and persist over the long-term course of the disease. The management of mucocutaneous lesions is important to prevent recurrence. We developed consensus guidelines that provide recommendations for general practitioners and dermatologists and physicians on the management of the mucocutaneous lesions of Behçet's disease.

DOI： 10.1111/1346-8138.15207

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: How HLA-A26 modulates Behçet's disease (BD) ocular lesions such as iridocyclitis and retinochorioiditis has not been scrutinized.Methods: Ministry of Health, Labour and Welfare of Japan provided us a database of BD patients who were registered from 2003 to 2014. We selected patients who satisfied International Criteria for BD and whose data for HLA-A26 was available.Results: Eligible 557 patients consisting of 238 men (42.7%) and 319 women (57.3%), whose median age was 38 years old (interquartile range 29-47) were analyzed. Prevalence of general ocular lesions, iridocyclitis, retinochorioiditis, and chronic lesions were 43.1%, 30.7%, 34.1%, and 17.4%, respectively. The prevalence of ocular lesions was higher among HLA-A26 carriers compared to that among HLA-A26 non-carriers with odds ratio (OR) of 2.5 (95% confidence interval (95% CI) 1.8-3.5, p < .001) for general ocular lesions, OR of 2.5 (95% CI 1.7-3.6, p < .001) for iridocyclitis, OR of 2.8 (95% CI 1.9-4.0, p < .001) for retinochorioiditis, and OR of 2.7 (95% CI 1.7-4.3, p < .001) for 'chronic ocular lesion following iridocyclitis or retinochorioiditis'. The HLA-A26 had a similar impact on ocular lesions between HLA-B51 positive and negative cases (Breslow-Day test, p > .05). However, the HLA-A26 had a larger impact on iridocyclitis for men compared to women (Breslow-Day test, p = .040). The male HLA-A26 carriers had higher risk of iridocyclitis with OR of 3.4 (95% CI 2.0-5.9, p < .001), while the OR for women was 1.5 (95% CI 0.9-2.6, p = .146).Conclusion: HLA-A26 carriers had higher risk for iridocyclitis and retinochorioiditis. However, the impact was more prominent for men.

DOI： 10.1080/14397595.2019.1705538

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1080/24725625.2019.1649857

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Igaku-Shoin Ltd  

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記述言語：英語  

BACKGROUND: Behçet's disease (BD) is a chronic multi-systemic vasculitis with a considerable prevalence in Asian countries. There are many genes associated with a higher risk of developing BD, one of which is endoplasmic reticulum aminopeptidase-1 (ERAP1). In this study, we aimed to investigate the interactions of ERAP1 single nucleotide polymorphisms (SNPs) using a novel data mining method called Model-based multifactor dimensionality reduction (MB-MDR). METHODS: We have included 748 BD patients and 776 healthy controls. A peripheral blood sample was collected, and eleven SNPs were assessed. Furthermore, we have applied the MB-MDR method to evaluate the interactions of ERAP1 gene polymorphisms. RESULTS: The TT genotype of rs1065407 had a synergistic effect on BD susceptibility, considering the significant main effect. In the second order of interactions, CC genotype of rs2287987 and GG genotype of rs1065407 had the most prominent synergistic effect (β = 12.74). The mentioned genotypes also had significant interactions with CC genotype of rs26653 and TT genotype of rs30187 in the third-order (β = 12.74 and β = 12.73, respectively). CONCLUSION: To the best of our knowledge, this is the first study investigating the interaction of a particular gene's SNPs in BD patients by applying a novel data mining method. However, future studies investigating the interactions of various genes could clarify this issue.

DOI： 10.1371/journal.pone.0227997

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Vogt-Koyanagi-Harada (VKH) disease is a systemic inflammatory disorder that affects pigment cell-containing organs such as the eye (e.g., chronic and/or recurrent granulomatous panuveitis). While the exact etiology and pathogenic mechanism of VKH disease are unclear, HLA-DR4 alleles have been documented to be strongly associated with VKH disease in various ethnic groups. Recently, a genome-wide association study (GWAS) found two new genetic risk factors (IL23R-C1orf141 and ADO-ZNF365-EGR2) in a non-HLA region from a Han Chinese population. In this study, we replicated these GWAS findings in a Japanese population. A total of 1,643 Japanese samples (380 cases with VKH disease and 1,263 healthy controls) were recruited. We assessed four single nucleotide polymorphisms (SNPs) shown in previous GWAS: rs78377598 and rs117633859 in IL23R-C1orf141, and rs442309 and rs224058 in ADO-ZNF365-EGR2. A significant allelic association with VKH disease was observed for all of the four SNPs (rs78377598: pc = 0.0057; rs117633859: pc = 0.0017; rs442309: pc = 0.021; rs224058: pc = 0.035). In genotypic association analysis, the minor alleles of IL23R-C1orf141 rs78377598 and rs117633859 had the strongest association with disease susceptibility under the additive model (pc = 0.0075 and pc = 0.0026, respectively). The minor alleles of ADO-ZNF365-EGR2 rs442309 and rs224058 were most strongly associated with disease susceptibility under the dominant model (pc = 0.00099 and pc = 0.0023, respectively). The meta-analysis of the current and previous studies found that all of the four SNPs exhibited a significantly strong association with VKH disease (meta-p < 0.00001: rs78377598, meta-odds ratio (OR) = 1.69; rs1176338, meta-OR = 1.82; rs442309, meta-OR = 1.34; rs224058, meta-OR = 1.33). In summary, our study replicated significant associations with VKH disease susceptibility reported in a previous GWAS. Thus, the IL23R-C1orf141 and ADO-ZNF365-EGR2 loci may play important roles in the development of VKH disease through genetic polymorphisms.

DOI： 10.1371/journal.pone.0233464

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Angiotensin-converting enzyme (ACE) is conventionally used as a biomarker in the diagnosis of uveitis associated with sarcoidosis, but its sensitivity is relatively low. In this study, we investigated whether serum soluble interleukin-2 receptor (sIL-2R) is also useful as a diagnostic marker, in addition to ACE, in the detection of uveitis associated with sarcoidosis. PATIENTS AND METHODS: Data were analyzed from 126 patients with uveitis (52 sarcoidosis and 74 non-sarcoid uveitis) and 12 with primary intraocular lymphoma (PIOL) who had their serum sIL-2R and ACE levels measured. RESULTS: Serum sIL-2R level was elevated in 69.2% of patients with sarcoid uveitis, 5.4% of those with non-sarcoid uveitis, and 16.7% of those with PIOL. The sensitivity and specificity of an elevated sIL-2R level for the detection of sarcoidosis were 69.2% and 93.0%, respectively. In contrast, serum ACE levels were elevated only in patients with sarcoid uveitis, with a sensitivity of 44.2% and specificity of 100%. Furthermore, serum sIL-2R and/or ACE level was elevated in 75.0% of patients with sarcoid uveitis, which is higher than those who had elevated serum ACE level only (44.2%, P = 0.0025). The sensitivity and specificity of elevated sIL-2R and/or ACE in detecting sarcoid uveitis were 75.0% and 93.0%, respectively. The PPV was 0.87, and the NPV was 0.86. CONCLUSION: Compared with the sensitivity of serum ACE levels alone, combined measurement of both serum sIL-2R and ACE levels improves sensitivity in the detection of uveitis associated with sarcoidosis. Nevertheless, serum ACE alone remains useful thanks to its high specificity in the differentiation of uveitis patients, with sarcoidosis from those without sarcoidosis.

DOI： 10.2147/OPTH.S264595

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Dove Medical Press Ltd  

DOI： 10.2147/IMCRJ.S271669

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Dove Medical Press Ltd  

DOI： 10.2147/IMCRJ.S280403

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objectives: To scrutinize the influence of HLA-B51 to each clinical manifestation of patients with Behçet's disease (BD) using a database of the Ministry of Health, Labour and Welfare of Japan. Methods: The database of newly registered patients with BD was obtained from the Japanese Ministry of Health, Labour and Welfare. Patients who met International Criteria for Behçet's Disease (ICBD) and had data for HLA-B51 were selected and analyzed. Results: Among the 3044 analyzable cases, 1334 (43.8%) were men and 1710 (56.2%) were women; the median age was 38 years (IQR 29-48). HLA-B51 was positive for 1334 (44.5%). Prevalence of selected manifestations was 98.5% for oral ulceration, 85.5% for skin lesion, 42.1% for ocular lesion, 69.1% for genital ulceration, and 29.0% for gastrointestinal symptom. HLA-B51-positive patients had higher risk for ocular lesion (OR 1.59, 95%CI: 1.37-1.84; p < .001) and lower risk for genital ulceration (OR 0.72, 95%CI: 0.62-0.84; p < .001) and gastrointestinal symptom (OR 0.65, 95%CI: 0.55-0.77; p < .001). No significant difference was observed for other organ involvement; oral ulceration, skin lesion, positive pathergy test, arthritis, epididymitis, vascular lesion, or neurological manifestation. Subgroup analyses revealed that HLA-B51 was not related to genital ulceration in the cases with an ICBD score of 6 or higher and that HLA-B51 tended to more largely affect the risk of three manifestations for men compared to that for women. Conclusion: HLA-B51 positive is a risk factor for ocular lesion and vice versa for genital ulceration and gastrointestinal symptoms in patients with Japanese BD.

DOI： 10.1080/14397595.2019.1649103

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Clinical data of patients with entro-, vasculo-, and neuro-variant possible Behçet's disease (BD) based on Japanese criteria has not yet comprehensively reported. Methods: This ongoing nation-wide registration has been carried out by the Japanese Ministry of Health, Labour and Welfare. The Ministry asked physicians who diagnosed a patient with confirmed or possible BD to register the patient data by filling out a registration form. The Ministry provided us with the dataset after unlinkable anonymization. We analyzed 2003-2014 database generated from the early stage new cases. Results: Among the 7950 analyzable cases, 694 (8.7%) had variant-type possible BD without satisfying complete/incomplete criteria. Of the 694 patients, 479, 46, and 169 had entero-, vasculo-, and neuro-variant possible BD, respectively. Out of these 694 patients, 35 (5.0%) and 154 (22.2%) satisfied the International Study Group criteria and the International Criteria of BD, respectively. Entero-variant possible patients rarely (1.8%) had ocular lesions. Patients with vasculo-variant possible BD were featured by low genital ulceration risk (6.8%) and frequent positive HLA-B51 (60.0%). Neuro-variant possible BD was featured by high median age at registration (48 year). Vasculo- (69.6%) and neuro-variant (68.6%) BD patients showed clear male dominance. Epididymitis was very rare among variant-type possible BD men. Conclusion: We analyzed 694 early-stage variant-type possible BD cases. We believe the data from our study will contribute to further international discussion regarding BD diagnostic criteria and clarification of the clinical presentations of the Japanese variant-type possible BD patients.

DOI： 10.1080/14397595.2018.1494501

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: To evaluate the clinical outcomes and features of Descemet's membrane endothelial keratoplasty (DMEK) for eyes with pseudoexfoliation syndrome (PEX). METHODS: In this retrospective study, 37 DMEK cases were reviewed from available medical records. Patients who exhibited endothelial dysfunction derived from PEX or Fuchs endothelial corneal dystrophy (FECD) and successfully underwent cataract surgery about four weeks before DMEK were enrolled. The best spectacle-corrected visual acuity (BSCVA), central corneal thickness (CCT), endothelial cell density (ECD), and incidence of intra-operative/post-operative complications of DMEK were analyzed. RESULTS: This study included 14 eyes of 14 patients (PEX: n = 6, FECD: n = 8). There was no primary graft failure. In the PEX group, BSCVA improved from 0.67 ± 0.28 at the preoperative point to 0.43 ± 0.14 at 1 month, 0.27 ± 0.10 at 3 months, and 0.19 ± 0.08 at 6 months after DMEK. The donor corneal ECD was 2704 ± 225 cells/mm2 at the preoperative point and decreased to 1691 ± 498 cells/mm2 at 1 month, 1425 ± 366 cells/mm2 at 3 months, and 1281 ± 340 cells/mm2 (52.7 ± 11.7% less than ECD of the donor graft) at 6 months after DMEK. None of the patients required rebubbling. When compared with the FECD group, no statistical difference was observed in CCT (p = 0.821); BSCVA (p = 0.001) and the reduction rate of ECD (p = 0.010) were relatively worse. CONCLUSIONS: DMEK is effective for the treatment of endothelial dysfunction due to PEX.

DOI： 10.1186/s12886-019-1130-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The strongest genetic risk factor of Behçet's disease (BD) is HLA-B*51. Our group previously reported that HLA-A*26 is independently associated with the risk of the onset of BD apart from HLA-B*51. Here, we re-evaluated the association between HLA-A*26 and BD in the Japanese population. We also performed a comprehensive literature search and meta-analyzed the extracted published data concerning the relationship between HLA-A*26 and BD to estimate the odds ratio (OR) of HLA-A*26 to BD. In this study, we genotyped 611 Japanese BD patients and 2,955 unrelated ethnically matched healthy controls. Genotyping results showed that the phenotype frequency of HLA-A*26 was higher in BD patients than in controls (OR = 2.12, 95% CI: 1.75-2.56). Furthermore, within the HLA-B*51-negative populations, the phenotype frequency of HLA-A*26 was significantly higher in BD patients than in controls (OR = 3.10, 95% CI: 2.43-3.95). Results obtained from meta-analysis combined with our data showed that the modified OR of HLA-A*26 became 1.80 (95% CI:1.58-2.06), whereas within the HLA-B*51-negative population, the modified OR became 4.02 (95% CI: 2.29-7.05). A subgroup analysis arranged by the geographical regions showed HLA-A*26 is in fact associated with the onset of BD in Northeast Asia (OR = 2.11, 95% CI: 1.75-2.56), but not in the Middle East or in Europe.

DOI： 10.1038/s41598-019-40824-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: This study aimed to identify patients with high-probability of ocular involvement of Behçet's disease (BD). METHODS: The Japanese Ministry of Health, Labour and Welfare provided dataset of ongoing nationwide BD registration project. A patient who had confirmed BD and who was suspected to have BD was registered. We mainly analyzed newly registered patients who had the data for all demographic and diagnostic parameters regardless of fulfilment of any diagnostic criteria. RESULTS: Among 3213 patients with confirmed or possible BD, 1382 (43.0%) were men and 1831 (57.0%) were women with a median age of 38 years (interquartile range (IQR) 30-49 years). The median duration between onset and registration was 0 year (IQR 0-3). A binomial multivariable logistic regression analysis revealed that being female (odds ratio (OR) 0.63, 95% confidence interval (CI) 0.53-0.75, p < .001), duration since onset (OR 1.33 per 10 years, 95% CI 1.18-1.51, p < .001), genital ulceration (OR 0.28, 95% CI 0.23-0.34, p < .001), and gastrointestinal symptoms (OR 0.36, 95% CI 0.30-0.44, p < .001) were related to the ocular lesion. Analyses based on data of 2800 patients who satisfied International criteria of BD, age-, sex-, duration-based subgroup analyses, analyses targeting iridocyclitis and retino-uveitis, and analysis including patients with missing data confirmed that the four factors were associated with the probability of eye involvement. CONCLUSION: The ocular involvement did not accompany with genital ulcer or gastrointestinal symptoms at the early stage of BD.

DOI： 10.1080/14397595.2018.1457424

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Noninfectious uveitis (NIU), which pathogenesis is often autoimmune nature, occurs as a symptom of systemic syndromes or only in the eye. The standard treatment of NIU is local, topical, and oral administration of corticosteroids (CS) in combination with immunomodulatory therapy (IMT). However, additional therapeutic strategies involving topical and systemic administration of CS or others to treat relapse or exacerbation of ocular inflammation in NIU which present as various ocular manifestations have not been established. The aim of this study was to investigate therapeutic strategies used for various ocular inflammations in relapse or exacerbation of NIU and to evaluate factors associated with the treatment pattern in Japan. The subjects were 198 eyes of 156 NIU patients with relapse or exacerbation of ocular inflammation at 6 university hospitals in Japan. The most frequent disease was sarcoidosis in 23.7% of the cases, followed by Behçet disease (BD) in 21.2%, Vogt-Koyanagi-Harada (VKH) disease in 13.6%, acute anterior uveitis (AAU) in 5.6%, tubulointerstitial nephritis and uveitis syndrome (TINU) in 4.0%, and juvenile idiopathic arthritis (JIA)-associated uveitis in 3.0%. Common ocular findings were worsened anterior inflammation (AI) in 67.2% of the cases, vitreous opacity (VO) in 46.5%, macular edema (ME) in 26.8%, retinal vasculitis (RV) in 23.7%, serous retinal detachment (SRD) in 9.1%, and optic perineuritis (OPN) in 4.0%. Reinforcement of betamethasone eye drop (ED) monotherapy for only AI in both unilateral and bilateral AI, sub-tenon injection of triamcinolone acetonide (STTA) for unilateral posterior inflammation including VO and ME, and systemic therapy using CS and/or IMT for bilateral anterior and posterior inflammation were significantly more frequent. Frequencies of exacerbated individual ocular findings in sarcoidosis and BD were similar, and severe ocular inflammation associated with panuveitis required both topical and systemic therapies. These results demonstrate that reinforcement of betamethasone EDs, topical administration of triamcinolone acetonide, and long-term administration of systemic corticosteroids are the major therapeutic strategies, and reinforcement of betamethasone EDs was used for exacerbated AI independently from its use for posterior inflammation. In addition, STTA was preferentially used for VO and ME associated with posterior inflammation.

DOI： 10.1097/MD.0000000000014668

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Report global adalimumab safety and efficacy outcomes in patients with non-infectious uveitis. METHODS: Adults with non-infectious intermediate, posterior, or panuveitis were randomized 1:1 to receive placebo or adalimumab in the VISUAL I (active uveitis) or VISUAL II (inactive uveitis) trials. Integrated global and Japan substudy results are reported. The primary endpoint was time to treatment failure (TF). RESULTS: In the integrated studies, TF risk was significantly reduced (hazard ratio [95% CI]) with adalimumab versus placebo (VISUAL I: HR = 0.56 [0.40-0.76], p < 0.001; VISUAL II: HR = 0.52 [0.37-0.74], p < 0.001). In Japan substudies, no consistent trends were observed between groups (VISUAL I: HR = 1.20 [0.41-3.54]; VISUAL II: HR = 0.45 [0.20-1.03]). Adverse event rates were similar between treatment groups in both studies (854 to 1063 events/100 participant-years). CONCLUSIONS: Adalimumab lowered time to TF versus placebo in the integrated population; no consistent trends were observed in Japan substudies. Safety results were consistent between studies.

DOI： 10.1080/09273948.2018.1491605

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose: Lattice degeneration of the retina is a vitreoretinal disorder characterized by a visible fundus lesion that predisposes the patient to retinal detachment. It has been suggested that collagen type II alpha 1 (COL2A1) gene variants may contribute to the development of disorders associated with retinal detachment. Here we investigated whether COL2A1 gene variants were associated with the risk of lattice degeneration of the retina. Methods: We recruited 634 Japanese patients with lattice degeneration of the retina and 1694 Japanese healthy controls. We genotyped 13 tagging single-nucleotide polymorphisms (SNPs) in COL2A1. We also performed imputation analysis to evaluate the potential association of un-genotyped COL2A1 SNPs, involving the imputation of 65 SNPs. Results: Two intronic SNPs-rs1793954 and rs1635533-were significantly associated with lattice degeneration of the retina. The SNP rs1793954 showed the strongest association, with its C allele carrying an increased disease risk (p = 0.0016, corrected p = 0.021, OR = 1.25). The rs1793954 and rs1635533 SNPs were in strong linkage disequilibrium with each other (r2 = 0.99), and conditional analysis revealed that rs1793954 could account for the association between rs1635533 and the disease. Conclusions: Our results suggested that COL2A1 gene variants may contribute to the development of lattice degeneration of the retina. Further genetic and functional analyses of COL2A1 variants are needed to clarify the present findings.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The recently emerged pachychoroid concept has changed the understanding of age-related macular degeneration (AMD), which is a major cause of blindness; recent studies attributed AMD in part to pachychoroid disease central serous chorioretinopathy (CSC), suggesting the importance of elucidating the CSC pathogenesis. Our large genome-wide association study followed by validation studies in three independent Japanese and European cohorts, consisting of 1546 CSC samples and 13,029 controls, identified two novel CSC susceptibility loci: TNFRSF10A-LOC389641 and near GATA5 (rs13278062, odds ratio = 1.35, P = 1.26 × 10-13; rs6061548, odds ratio = 1.63, P = 5.36 × 10-15). A T allele at TNFRSF10A-LOC389641 rs13278062, a risk allele for CSC, is known to be a risk allele for AMD. This study not only identified new susceptibility genes for CSC, but also improves the understanding of the pathogenesis of AMD.

DOI： 10.1038/s42003-019-0712-z

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記述言語：英語  

Zonulopathy is a major concern if found during cataract surgery as it can cause further complications. Such complications may occur during continuous curvilinear capsulorhexis (CCC), lens fragmentation and intraocular lens (IOL) implantation. Femtosecond laser-assisted cataract surgery (FLACS) devices, such as the LenSX (Alcon Laboratories) are advantageous because they can detect the area and largest point of zonulopathy via anterior segment optical coherent tomography (AS-OCT) before the manual part of the procedure. CCC and lens fragmentation can also minimize further zonular stress. A symmetrical CCC is ideal for IOL implantation in the sulcus with optic capture. In the present study, we did not detect significant zonular dehiscence preoperatively in either of the eyes of our 68-year-old patient when using AS-OCT (CASIA2 Tomey). However, LenSx AS-OCT revealed zonular dehiscence in both eyes, perioperatively. We created CCC and lens fragmentation without causing stress to the zonules. In the subsequent manual part of procedure, we found zonular dehiscence in the same area as indicated by LenSx AS-OCT, which extended to approximately 200° in the right eye and 180° in the left. After lens fragmentation by LenSx, we successfully removed the lens without further zonular dialysis. However, zonular dialysis (>180°) in the right eye was too large to insert an IOL, either in the capsule or the sulcus. Therefore, we performed scleral IOL implantation. In the left eye, we avoided using capsular tension ring (CTR) for IOL placement to avoid further iatrogenic damage to the zonule. Instead, an IOL was inserted into the sulcus with optic capture to reduce the possibility of further stress to the zonula and phimosis. Post-surgically, the patient regained good eyesight in both eyes. This case illustrates the advantages of FLACS in addressing zonulopathy. The consistent creation of CCC and lens fragmentation by FLACS may increase success rates, even in unexpectedly challenging cases.

DOI： 10.2147/IMCRJ.S189367

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose: To investigate whether variants in the ARMC9 gene encoding KU-MEL-1 are associated with Vogt-Koyanagi-Harada (VKH) disease in a Japanese population. Methods: We recruited 380 Japanese patients with VKH disease and 744 Japanese healthy controls to genotype seven single-nucleotide polymorphisms (SNPs) in ARMC9. We also performed imputation analysis of the ARMC9 region and 195 imputed SNPs were included in the statistical analysis. Results: We observed an increased frequency of the A allele of rs28690417 in patients compared with controls (P = 0.0097, odds ratio (OR) = 1.46). The A allele had a dominant effect on VKH disease risk (P = 0.011, OR = 1.51). However, these significant differences disappeared after Bonferroni correction (corrected P > 0.05). The remaining 201 SNPs did not show any significant association with disease risk. Conclusions: Our study suggests that ARMC9 variants do not play a critical role in the development of VKH disease.

DOI： 10.1080/09273948.2018.1523438

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Takayasu arteritis (TAK) is a systemic vasculitis with severe complications that affects the aorta and its large branches. HLA-B*52 is an established susceptibility locus to TAK. To date, there are still only a limited number of reports concerning non-HLA susceptibility loci to TAK. We conducted a genome-wide association study (GWAS) and a follow-up study in a total of 633 TAK cases and 5,928 controls. A total of 510,879 SNPs were genotyped, and 5,875,450 SNPs were imputed together with HLA-B*52. Functional annotation of significant loci, enhancer enrichment, and pathway analyses were conducted. We identified four unreported significant loci, namely rs2322599, rs103294, rs17133698, and rs1713450, in PTK2B, LILRA3/LILRB2, DUSP22, and KLHL33, respectively. Two additional significant loci unreported in non-European GWAS were identified, namely HSPA6/FCGR3A and chr21q.22. We found that a single variant associated with the expression of MICB, a ligand for natural killer (NK) cell receptor, could explain the entire association with the HLA-B region. Rs2322599 is strongly associated with the expression of PTK2B Rs103294 risk allele in LILRA3/LILRB2 is known to be a tagging SNP for the deletion of LILRA3, a soluble receptor of HLA class I molecules. We found a significant epistasis effect between HLA-B*52 and rs103294 (P = 1.2 × 10-3). Enhancer enrichment analysis and pathway analysis suggested the involvement of NK cells (P = 8.8 × 10-5, enhancer enrichment). In conclusion, four unreported TAK susceptibility loci and an epistasis effect between LILRA3 and HLA-B*52 were identified. HLA and non-HLA regions suggested a critical role for NK cells in TAK.

DOI： 10.1073/pnas.1808850115

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記述言語：英語  

Behçet's Disease (BD) pathogenesis remains unclear, but some genetic loci and environmental factors are proposed to play a role. Here, we investigate the association of the endoplasmic reticulum aminopeptidase-1 (ERAP1) gene variants and HLA-B*51 with BD susceptibility and clinical manifestations in Iranian patients. In the study, 748 BD patients and 776 healthy individuals were included. The MGB-TaqMan Allelic Discrimination method was used to genotype 10 common missense single nucleotide polymorphisms (SNPs) and one intronic SNP in the ERAP1 gene region. We found no significant association between the 11 SNPs and BD in allelic and genotypic association tests. However, rs30187 showed the strongest association with BD in the recessive genotype model of the risk T allele in HLA-B*51 carriers. Although this became insignificant after correcting for multiple comparisons, the homozygous rs30187 risk allele genotype (TT) increased disease susceptibility in HLA-B*51 carriers in epistasis analysis, and the rs30187 TT recessive genotype showed a significant association with risk of cardiac involvement in the all patients and articular involvements in HLA-B*51 positive patients. Our findings suggest that gene-gene interactions between HLA-B*51 and ERAP1 variants is important for BD development, however, ERAP1 variants which interact with HLA-B*51 may differ among disease phenotypes or populations.

DOI： 10.1038/s41598-018-35700-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Sarcoidosis is a major cause of granulomatous uveitis but rarely manifests as multiple choroidal granulomas. This report describes the use of enhanced depth imaging optical coherence tomography (EDI-OCT) to visualize changes occurring in multiple choroidal granulomas during treatment. METHODS: The patient was a 36-year-old Japanese man with histopathologically confirmed sarcoidosis, who was examined using EDI-OCT and showed multiple yellowish-white subretinal lesions in the peripapillary region and the arcade of the right eye. RESULTS: EDI-OCT revealed homogeneous hyporeflective choroidal lesions with choriocapillaris thinning, consistent with a diagnosis of choroidal granulomas. Subretinal fluid adjacent to one of the peripapillary choroidal lesions was also apparent. EDI-OCT during oral prednisolone administration revealed a decrease in lesion size at as early as 3 weeks and complete resolution of the lesions after 6 months of treatment. However, 2 months after prednisolone discontinuation, EDI-OCT revealed recurrence of choroidal granulomas in the peripapillary region and the arcade of the right eye. After injection of triamcinolone acetonide into the posterior sub-Tenon's capsule (sub-Tenon's injection), EDI-OCT demonstrated a reduction in granuloma lesion size within 3 months of the injection. CONCLUSION: EDI-OCT allowed detailed morphologic visualization of the choroidal granulomas caused by sarcoidosis. This imaging technique was useful for monitoring changes in granuloma size in response to steroid administration and for early detection of recurrence. Injection of triamcinolone acetonide into the posterior sub-Tenon's capsule was as effective as oral prednisolone for the treatment of choroidal granulomas.

DOI： 10.1007/s10792-017-0720-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To evaluate the frequency and severity of iris posterior synechiae after Descemet membrane endothelial keratoplasty (DMEK) and to investigate possible causes of iris posterior synechiae. METHODS: Twenty-three eyes were investigated in 20 Asian patients who underwent DMEK 1 month after phacoemulsification and intraocular lens implantation surgery. A preexisting iris damage score was defined by iris damage and classified into 5 grades. Six months after DMEK, the iris posterior synechiae severity score was evaluated based on the extent of posterior synechiae, according to every 45 degrees of the pupillary rim (posterior synechiae score, 0-8). Correlations were analyzed between the posterior synechiae score and preexisting factors (preexisting iris damage score, axial length [AXL], anterior chamber depth, and anterior chamber volume, both before and after cataract surgery). RESULTS: Iris posterior synechiae appeared in 20 of 23 eyes (87.0%). Best spectacle-corrected visual acuity significantly improved at 6 months after DMEK (P < 0.001). Endothelial cell density was 1596 ± 530 cells/mm (P < 0.001); loss of cell density was 37.8 ± 19.9% at 6 months. Single regression analysis showed that the onset of iris posterior synechiae was correlated with the preexisting iris damage score (P = 0.006, r = 0.55), AXL (P < 0.001, r = -0.71), anterior chamber depth (P < 0.001, r = -0.70), and anterior chamber volume before cataract surgery (P < 0.001, r = -0.79). CONCLUSIONS: Iris posterior synechiae after DMEK frequently appeared in Asian eyes with shorter AXLs or a damaged iris.

DOI： 10.1097/ICO.0000000000001698

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記述言語：英語  

BACKGROUND: Neurosarcoidosis is a rare complication, and cranial neuropathy is the most frequent manifestation of this disease. However, few cohesive reports have discussed multiple cranial neuropathies in Japanese patients with sarcoidosis. The present report discusses the case of a patient with sarcoid uveitis and multiple neurological findings. We further review relevant literature regarding Japanese patients with multiple cranial nerve palsies published within the past 34 years (from January 1982 to December 2016). CASE PRESENTATION: We report findings associated with the case of a 56-year-old Japanese woman with granulomatous pan-uveitis who was later diagnosed as having sarcoidosis by skin and transbronchial lung biopsies. She presented right-sided Bell's palsy and was treated with orally administered prednisolone. However, while prednisolone was tapered, she developed facial (VII) and vagus (X) nerve palsies, followed by brain parenchyma lesions, which were not associated with any additional neurological symptoms. Furthermore, she exhibited increased intraocular pressure in her right eye, and she underwent trabeculectomy. Our review of the literature revealed that 64 Japanese patients with sarcoidosis experienced multiple cranial nerve palsies between 1982 and 2016. The most commonly affected cranial nerves were the facial (VII) (73.4%) and glossopharyngeal/vagus (IX/X) nerves (48.4%). Palsies of two distinct cranial nerves were found in 40.6% of the patients, followed by palsies of three (23.4%) and four (18.8%) nerves. Almost all patients (98.3%) received systemic steroid therapy, and total or partial remission was achieved in almost all patients (96.5%). CONCLUSIONS: According to the literature, patients with multiple cranial nerve palsies associated with sarcoidosis respond well to orally administered steroid therapy. However, our findings suggest that careful follow-up is necessary for patients with neurosarcoidosis due to potential aggravation of neuropathy.

DOI： 10.1186/s13256-018-1842-5

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Igaku-Shoin Ltd  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Igaku-Shoin Ltd  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Igaku-Shoin Ltd  

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

DOI： 10.1038/s41588-018-0127-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Graft insertion into the anterior chamber is one of the most important procedures for successful Descemet membrane endothelial keratoplasty (DMEK). Especially in eyes with fragile zonular fibers and a shallow anterior chamber, smooth graft insertion tends to become more difficult. Ophthalmic viscoelastic devices (OVDs) can usually help to retain the space in the anterior chamber and to improve the safety of manipulations during various ophthalmic surgeries. Therefore, we postulated that graft insertion into the anterior chamber could be improved by their use. The purpose of this study is to investigate the availability and efficacy of OVDs during graft insertion in DMEK surgery.A total of 11 eyes of 9 patients with bullous keratopathy who underwent DMEK were retrospectively analyzed. The cause of bullous keratopathy was corneal endothelial decompensation following laser iridotomy in all eyes. We used low viscous dispersive OVD (Opegan) to maintain the anterior chamber depth during graft insertion in all of the eyes.The graft insertion was uneventful in all of the eyes. The inserted graft was attached to the back surface of the cornea. However, 2 eyes needed rebubbling, and after rebubbling, all of the 2 grafts completely attached to the back surface of the cornea. The best spectacle-corrected visual acuity significantly improved 6 months after surgery (P < .001) and the central corneal thickness significantly decreased (P < .001).The use of OVD facilitates safer graft insertion during DMEK, and subsequently prevents endothelial cell loss, which leads to a successful procedure.

DOI： 10.1097/MD.0000000000011245

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記述言語：英語  

At present, only one design is available for trifocal intraocular lens (IOL); unfortunately, this particular design is not suitable for implantation in the sulcus with optic capture when posterior capsule rupture (PCR) occurs. Although three-piece bifocal IOLs can be implanted in the sulcus, this form of IOL can be vulnerable to tilt and decentration, thus causing aberration and photopic phenomena, such as halos and glares. However, visual axis centered optic capture using femtosecond laser-assisted cataract surgery (FLACS) is able to manage such complex operations. In the present study, we implanted a three-piece +4.0 D bifocal IOL into the sulcus of a patient who experienced PCR using optic capture and FLACS following the straightforward implantation of a one-piece trifocal IOL in the other eye. Defocus curves showed that the weakness of the trifocal IOL (nearest distances) was compensated for by the strength of the +4.0 D bifocal IOL, whereas the weakness of the +4.0 D bifocal IOL (middle distance) was compensated for by the strength of the trifocal IOL. Therefore, this combination provided the patient with a wider range of depth of focus. The contrast sensitivity in both eyes was within the normal range. Photopic phenomena were comparable with the bilateral implantation of the trifocal IOL. Anterior segment optical coherence tomography showed that tilt and decentration in the trifocal IOL implanted in the bag was significantly higher than the +4.0 D bifocal IOL implanted in the visual axis centered optic capture. This case showed that the intraindividual implantation of a single-piece trifocal IOL in the bag and a three-piece +4.0 D bifocal IOL in the sulcus, using a combination of optic capture and FLACS, is promising particularly in cases of PCR and can provide a wider range of vision without losing visual quality.

DOI： 10.2147/IMCRJ.S176095

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記述言語：英語  

Purpose: To evaluate the influence of pupil dilation on predicted postoperative refraction (PPR) and recommended intraocular lens (IOL) power to obtain target postoperative refraction calculated by using the third- and fourth-generation IOL power calculation formulas with a new optical biometer. Methods: This retrospective study included 162 eyes with cataract that underwent uneventful phacoemulsification with IOL implantation. PPR, recommended IOL power, anterior chamber depth (ACD), and lens thickness (LT) were measured pre- and post-pupil dilation. The change in PPR detected by using third-generation (Hoffer Q and SRK/T) and fourth-generation formulas (Haigis and Holladay 2) and the changes in ACD and LT were evaluated pre- and postdilation. The influence of dilation on the recommended IOL power calculated by each formula was analyzed. Result: ACD and LT significantly changed from pre- to postdilation. The mean absolute change in PPR between pre- and postdilation was significantly higher for fourth-generation formulas compared with third-generation formulas. The change in PPR between pre- and postdilation showed a significantly positive correlation with change in ACD and a significantly negative correlation with change in LT with fourth-generation formulas, but not with third-generation formulas. The discrepancy rate of recommended IOL power between pre- and postdilation calculated by fourth-generation formulas was significantly higher than that calculated by third-generation formulas. Conclusion: ACD and LT significantly changed by dilation. PPR and recommended IOL power significantly changed more by dilation when using fourth-generation formulas compared with third-generation formulas. Given the significant correlations of the change in PPR (between the pre- and postdilation) in the fourth-generation formulas and the changes in ACD and LT, the latter changes may be key in influencing dilation in the fourth-generation power calculation. Knowledge of the influence of dilation on fourth-generation formulas could help improve IOL calculation.

DOI： 10.2147/OPTH.S172846

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objective: This report aimed to scrutinize the prevalence of Behçet's disease (BD)-related clinical manifestations based on age- and sex-specific subgroups using a Japanese nationwide registration database. Methods: The database of newly registered BD was obtained from the Japanese Ministry of Health, Labour and Welfare. Patients who met the International Criteria for Behçet's Disease were selected and analysed. Results: Among 6627 International Criteria for Behçet's Disease cases, 2651 (40.0%) were men and 3976 (60.0%) were women with a median age of 39 years (interquartile range: 31-50 years). Ocular lesion was more common in male [odds ratio (male: female) 2.64 (95% CI: 2.35, 2.95, P < 0.001)] and genital ulceration was more common in female (odds ratio = 0.29, 95% CI: 0.25, 0.32, P < 0.001). Ocular lesion (P < 0.001), arthritis (P < 0.001) and vascular lesions (P < 0.001) were more frequently observed in elderly registered patients. Contrarily, genital ulceration (P < 0.001), epididymitis of males (P = 0.023) and oral ulceration (P = 0.003) were more common in younger patients. Simultaneous assessment of sex and age revealed that male predominance of ocular involvement was found in the young adult generation, but not in patients over 70 year of age. A female predominance of genital ulcer was prominently observed in patients 20-59 year of age; however, the sex difference was not found in patients over 60 years of age. Sensitivity analysis using International Study Group criteria replicated the results. Conclusion: We showed that clinical phenotype in early phase of BD was different depending on onset age and sex.

DOI： 10.1093/rheumatology/kex285

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To describe a simple technique that uses posterior chandelier illumination during Descemet membrane endothelial keratoplasty in cases of severe bullous keratopathy (BK). METHODS: Five eyes of 4 patients with advanced BK undergoing Descemet membrane endothelial keratoplasty were retrospectively analyzed. The pupil of the host eye was not treated with mydriatic or miotic agents. The chandelier illuminator was inserted transconjunctivally into the vitreous cavity from the pars plana. RESULTS: In all eyes, BK was secondary to laser iridotomy, which was performed for prevention or treatment of angle closure glaucoma. The implanted graft was clearly confirmed in the anterior chamber using activated chandelier illumination. The graft was immediately attached to the host cornea, with eventual healing of BK in all eyes. No complication involving insertion or removal of the 25-gauge trocar and the chandelier illuminator was observed. No vision-threatening complication was observed in any of the 5 eyes. CONCLUSIONS: The chandelier illuminator provided good visibility of the anterior chamber and enhanced the safety of surgery by preventing formation of an inverted graft.

DOI： 10.1097/ICO.0000000000001254

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Neuro-Behçet's disease (NBD) is subcategorized into parenchymal-NBD (P-NBD) and non-parenchymal-NBD types. Recently, P-NBD has been further subdivided into acute P-NBD (A-P-NBD) and chronic progressive P-NBD (CP-P-NBD). Although an increasing number of studies have reported the various clinical features of A-P-NBD and CP-P-NBD over the last two decades, there was a considerable inconsistency. Two investigators systematically searched four electrical databases to detect studies that provided sufficient data to assess the specific characteristics of A-P-NBD and CP-P-NBD. All meta-analysis was carried out by employing the random-model generic inverse variance method. We included 11 reports consisted of 184 A-P-NBD patients and 114 CP-P-NBD patients. While fever (42% for A-P-NBD, 5% for CP-P-NBD, p < 0.001, I2 = 93%) was more frequently observed in A-P-NBD cases; sphincter disturbances (9%, 34%, P = 0.005, I2 = 87%), ataxia (16%, 57%, P < 0.001, I2 = 92%), dementia (7%, 61%, P < 0.001, I2 = 97%), confusion (5%, 18%, P = 0.04, I2 = 76%), brain stem atrophy on MRI (4%, 75%, P < 0.001, I2 = 98%), and abnormal MRI findings in cerebellum (7%, 54%, P = 0.02, I2 = 81%) were more common in CP-P-NBD. Cerebrospinal fluid cell count (94/mm3, 11/mm3, P = 0.009, I2 = 85%) was higher in A-P-NBD cases. We demonstrated that A-P-NBD and CP-P-NBD had clearly different clinical features and believe that these data will help future studies investigating P-NBD.

DOI： 10.1038/s41598-017-09938-z

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記述言語：英語  

DOI： 10.1007/s10792-016-0321-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/s41598-017-00877-3

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記述言語：英語  

DOI： 10.3109/13816810.2016.1145698

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/ng.3786

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記述言語：英語  

DOI： 10.3109/09273948.2015.1136422

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose: The crystallin beta A4 (CRYBA4) gene variant, rs2009066, was previously reported to be associated with high myopia in a southern Chinese population. In the present study, we investigated whether CRYBA4 variants were associated with high myopia in a Japanese population. Methods: We recruited 1,063 Japanese patients with high myopia (spherical equivalent [SE] ≤-9.00 D in both eyes) and 1,009 healthy Japanese subjects (SE >-1.00 D). We genotyped rs2009066 and three tagging single-nucleotide polymorphisms (SNPs), rs16982456, rs2071861, and rs4276, in the CRYBA4 region. Results: We did not find any significant association between these four SNPs and high myopia in an allele analysis. However, rs2009066 and rs2071861, which were in strong linkage disequilibrium (LD; r2=0.86), showed a marginal association with high myopia in the recessive genotype model of risk alleles (rs2009066 G allele: P=0.032, odds ratio [OR] =1.31; rs2071861 A allele: P=0.037, OR =1.31). Nevertheless, this association became insignificant after correcting for multiple testing (Pc >0.05). Conclusion: This study showed no significant association between CRYBA4 variants and high myopia in a Japanese population. Our findings did not correspond with a previous study. Further genetic studies with other populations are needed to elucidate a potential contribution of the CRYBA4 region in the development of high myopia.

DOI： 10.2147/OPTH.S146038

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Introduction: Maintaining the correct orientation of the donor graft is important during Descemet's membrane endothelial keratoplasty (DMEK). We describe a new method of marking the donor graft prior to DMEK. Methods: Twelve eyes of 10 patients with bullous keratopathy who underwent DMEK were retrospectively analysed. Donor discs were created by stripping the endothelium-Descemet's membrane layer from corneoscleral buttons. Four semicircular marks, two 1.0 mm and two 1.5 mm in diameter, were created at the edge of the donor disc. The small and large marks were paired. Each donor graft was inserted into the anterior chamber, unfolded and attached to the posterior corneal stroma with an air bubble. Results: The inserted grafts were all appropriately orientated when attached to the back surfaces of the corneas. The two pairs of asymmetric marks afforded valuable guidance. Even when the graft was partially folded or decentred, and one pair of marks was obscured, the other pair was always visible to indicate graft orientation. Best spectacle-corrected visual acuity improved significantly in all patients (p<0.001). Compared with the preoperative endothelial cell density of the donor graft, that of the corneal endothelium had decreased 44.0%±10.0% by 6 months after surgery. Conclusions: Two pairs of asymmetrical semicircular marks placed on the edge of the donor graft allowed appropriate graft orientation during DMEK.

DOI： 10.1136/bmjophth-2017-000080

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3109/13816810.2015.1028649

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記述言語：英語  

DOI： 10.1111/1346-8138.13251

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

DOI： 10.1038/srep25853

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s10384-016-0441-5

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記述言語：英語  

DOI： 10.1038/ncomms11008

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

Components of fish roe possess antioxidant and antiaging activities, making them potentially very beneficial natural resources. Here, we investigated chum salmon eggs (CSEs) as a source of active ingredients, including vitamins, unsaturated fatty acids, and proteins. We incubated human dermal fibroblast cultures for 48 hours with high and low concentrations of CSE extracts and analyzed changes in gene expression. Cells treated with CSE extract showed concentration-dependent upregulation of collagen type I genes and of multiple antioxidative genes, including OXR1, TXNRD1, and PRDX family genes. We further conducted in silico phylogenetic footprinting analysis of promoter regions. These results suggested that transcription factors such as acute myeloid leukemia-1a and cyclic adenosine monophosphate response element-binding protein may be involved in the observed upregulation of antioxidative genes. Our results support the idea that CSEs are strong candidate sources of antioxidant materials and cosmeceutically effective ingredients.

DOI： 10.2147/CIA.S102092

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2147/OPTH.S104761

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語  

DOI： 10.1371/journal.pone.0160392

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2147/CIA.S102092

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.bbi.2015.05.003

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記述言語：英語  

DOI： 10.1038/ejhg.2014.288

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記述言語：日本語   掲載種別：研究論文（国際会議プロシーディングス）   出版者・発行元：Igaku-Shoin Ltd  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Igaku-Shoin Ltd  

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記述言語：英語  

DOI： 10.1038/ejhg.2014.158

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/ncomms7689

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記述言語：英語  

For the purpose of investigating Behcet&#039;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&#039;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 ocula

DOI： 10.1007/s10067-013-2442-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s10067-013-2442-9

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記述言語：英語   掲載種別：論文集(書籍)内論文   出版者・発行元：Springer Japan  

DOI： 10.1007/978-4-431-54487-6_3

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記述言語：英語  

DOI： 10.1007/s10384-014-0362-0

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記述言語：英語  

DOI： 10.3980/j.issn.2222-3959.2015.01.01

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記述言語：日本語   出版者・発行元：日本サルコイドーシス/肉芽腫性疾患学会  

【目的】今回、サルコイドーシス(サ症)診断基準の全身検査項 目に、血清可溶性 IL-2 受容体(s IL-2R)が加わった。血清 s IL-2R はサ症の他、悪性リンパ腫や膠原病、結核などでも上昇すること が知られている。我々は、ぶどう膜炎患者における血清 s IL-2R 測定が、サ症鑑別・診断に有用か否かを検討した。 【対象・方法】2014 年 8 月から 2015 年 5 月までに当院眼科外来 を受診し、確定診断がついたサ症 43 例、眼内悪性リンパ腫 10 例、 サ症以外の原因の明らかなぶどう膜炎 48 例について、ERISA 法 にて血清 s IL-2R を測定した。 【結果】血清 s IL-2R (Cut-Off 値:534U/ml)はサ症では 31 例 (72.1%、平均値:913.7 U/ml)、眼内悪性リンパ腫では 2 例(20%、 平均値:521 U/ml)、サ症以外のぶどう膜炎では 3 例(6.3%)に上 昇が見られた。サ症における血清 s IL-2R の感度は 72.1%、特異 度は 91.4%であった。 【結論】眼内悪性リンパ腫との鑑別を考慮に入れる必要はあるが、 血清 s IL-2R 測定は、サ症に伴うぶどう膜炎を鑑別・診断するた めに有用であると考えられた。

DOI： 10.7878/jjsogd.35.Suppl1_50-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3109/09273948.2014.981547

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2147/OPTH.S95167

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.ophtha.2014.04.042

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記述言語：英語  

DOI： 10.1007/s10792-013-9878-4

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記述言語：英語  

DOI： 10.1111/aos.12349

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記述言語：英語  

DOI： 10.1007/s00417-014-2616-4

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記述言語：英語  

DOI： 10.1007/s00417-014-2597-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s10384-013-0294-0

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Igaku-Shoin Ltd  

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記述言語：英語   掲載種別：論文集(書籍)内論文   出版者・発行元：Springer Nature  

DOI： 10.1007/978-88-470-5477-6_4

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Igaku-Shoin Ltd  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Igaku-Shoin Ltd  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Igaku-Shoin Ltd  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Igaku-Shoin Ltd  

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記述言語：英語  

DOI： 10.1007/s00417-013-2469-2

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記述言語：英語  

DOI： 10.1007/s00417-013-2419-z

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記述言語：英語  

DOI： 10.1136/annrheumdis-2011-200288

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記述言語：英語  

DOI： 10.1007/s00417-012-2232-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.5301/ejo.5000252

Web of Science

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記述言語：英語  

DOI： 10.1016/j.ajhg.2013.06.016

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記述言語：英語  

DOI： 10.1136/bjophthalmol-2012-302289

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3109/09273948.2012.756114

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1073/pnas.1306352110

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記述言語：英語  

DOI： 10.3109/09273948.2012.747619

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記述言語：英語  

DOI： 10.1136/bjophthalmol-2012-302704

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/ng.2520

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s10384-012-0211-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1371/journal.pone.0074372

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記述言語：日本語   掲載種別：研究論文（国際会議プロシーディングス）  

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記述言語：日本語   掲載種別：研究論文（国際会議プロシーディングス）  

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記述言語：日本語   掲載種別：研究論文（国際会議プロシーディングス）  

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記述言語：日本語   掲載種別：研究論文（国際会議プロシーディングス）  

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

DOI： 10.1038/eye.2013.123

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2147/OPTH.S52726

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記述言語：英語  

DOI： 10.1159/000354611

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記述言語：英語  

DOI： 10.1097/ICO.0b013e3182408bc7

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1167/iovs.12-10491

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記述言語：英語  

DOI： 10.1177/1550059412445608

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記述言語：英語  

DOI： 10.1136/bjophthalmol-2011-300864

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s10384-012-0150-7

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記述言語：英語  

DOI： 10.1007/s00417-011-1921-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/hr.2012.41

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

As one of the leading causes of visual impairment and blindness, myopia poses a significant public health burden in Asia. The primary determinant of myopia is an elongated ocular axial length (AL). Here we report a meta-analysis of three genome-wide association studies on AL conducted in 1,860 Chinese adults, 929 Chinese children, and 2,155 Malay adults. We identified a genetic locus on chromosome 1q41 harboring the zinc-finger 11B pseudogene ZC3H11B showing genome-wide significant association with AL variation (rs4373767, beta = -0.16 mm per minor allele, P-meta = 2.69x10(-10)). The minor C allele of rs4373767 was also observed to significantly associate with decreased susceptibility to high myopia (per-allele odds ratio (OR) = 0.75, 95% CI: 0.68-0.84, P-meta = 4.38x10(-7)) in 1,118 highly myopic cases and 5,433 controls. ZC3H11B and two neighboring genes SLC30A10 and LYPLAL1 were expressed in the human neural retina, retinal pigment epithelium, and sclera. In an experimental myopia mouse model, we observed significant alterations to gene and protein expression in the retina and sclera of the unilateral induced myopic eyes for the murine genes ZC3H11A, SLC30A10, and LYPLAL1. This supports the likely role of genetic variants at chromosome 1q41 in influencing AL variation and high myopia.

DOI： 10.1371/journal.pgen.1002753

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3109/09273948.2012.665124

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記述言語：英語  

DOI： 10.1093/rheumatology/ker444

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.5301/ejo.5000032

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記述言語：英語  

DOI： 10.1097/ICO.0b013e3181dc81d2

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記述言語：英語  

DOI： 10.1016/j.exer.2011.12.021

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.exer.2011.12.021

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記述言語：英語  

DOI： 10.1007/s00417-011-1800-z

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記述言語：英語  

DOI： 10.1016/j.bbrc.2012.01.033

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語  

DOI： 10.1371/journal.pgen.1002753

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1371/journal.pone.0039300

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記述言語：英語  

DOI： 10.1097/ICU.0b013e32834bbd7e

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語  

DOI： 10.3109/09273948.2011.553981

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記述言語：英語  

DOI： 10.1159/000329190

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Juvenile idiopathic arthritis (JIA) is one of the most common forms of pediatric chronic arthritis. JIA is a clinically heterogeneous disease. Therefore, the genetic background of JIA may also be heterogeneous. The aim of this study was to investigate associations between human leukocyte antigen (HLA) and susceptibility to JIA and/or uveitis, which is one of the most devastating complications of JIA. A total of 106 Japanese articular JIA patients (67 with polyarthritis and 39 with oligoarthritis) and 678 healthy controls were genotyped for HLA-A, -B and -DRB1 by PCR-sequence-specific oligonucleotide probe methodology. HLA-A(*)02:06 was the risk factor for JIA accompanied by uveitis after adjustment for clinical factors (corrected P-value < 0.001, odds ratio (OR) 11.7, 95% confidence interval (CI) 3.2-43.0). On the other hand, HLA-DRB1(*)04:05 was associated with polyarticular JIA (corrected P-value < 0.001, OR 2.9, 95% CI 1.7-4.8). We found an association of HLA-A(*)02:06 with susceptibility to JIA accompanied by uveitis, which might be considered a separate clinical JIA entity. We also found an association between HLA-DRB1(*)04:05 and polyarticular JIA. Thus, clinical subtypes of JIA can be classified by the presence of the specific HLA alleles, HLA-A(*)02:06 and DRB1(*)04:05.

DOI： 10.1038/jhg.2010.159

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Juvenile idiopathic arthritis (JIA) is one of the most common forms of pediatric chronic arthritis. JIA is a clinically heterogeneous disease. Therefore, the genetic background of JIA may also be heterogeneous. The aim of this study was to investigate associations between human leukocyte antigen (HLA) and susceptibility to JIA and/or uveitis, which is one of the most devastating complications of JIA. A total of 106 Japanese articular JIA patients (67 with polyarthritis and 39 with oligoarthritis) and 678 healthy controls were genotyped for HLA-A, -B and -DRB1 by PCR-sequence-specific oligonucleotide probe methodology. HLA-A(*)02:06 was the risk factor for JIA accompanied by uveitis after adjustment for clinical factors (corrected P-value &lt; 0.001, odds ratio (OR) 11.7, 95% confidence interval (CI) 3.2-43.0). On the other hand, HLA-DRB1(*)04:05 was associated with polyarticular JIA (corrected P-value &lt; 0.001, OR 2.9, 95% CI 1.7-4.8). We found an association of HLA-A(*)02:06 with susceptibility to JIA accompanied by uveitis, which might be considered a separate clinical JIA entity. We also found an association between HLA-DRB1(*)04:05 and polyarticular JIA. Thus, clinical subtypes of

DOI： 10.1038/jhg.2010.159

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記述言語：英語  

DOI： 10.1016/j.humimm.2010.12.007

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.bbrc.2010.09.088

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語  

Behçet&#039;s disease is a chronic systemic inflammatory disorder characterized by four major manifestations: recurrent ocular symptoms, oral and genital ulcers and skin lesions. We conducted a genome-wide association study in a Japanese cohort including 612 individuals with Behçet&#039;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).

DOI： 10.1038/ng.624

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/ng.624

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記述言語：英語  

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記述言語：英語  

DOI： 10.1016/j.ophtha.2009.12.001

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記述言語：英語  

DOI： 10.1136/ard.2009.108571

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語  

DOI： 10.1016/j.clinph.2009.12.005

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/gt.2009.122

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/ar3005

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/nm.2018

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1167/iovs.08-2530

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DOI： 10.1097/IAE.0b013e3181a3b946

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記述言語：英語  

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記述言語：英語  

DOI： 10.1093/rheumatology/kep077

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Beta-tricalcium phosphate (beta-TCP) was grafted into rat mandibular bone defects to assess its potential as a scaffold material for bone regeneration. For this purpose, beta-TCP (TCP), allogenic bone (Allograft), and allogenic bone combined with beta-TCP (Combined) were employed as graft materials. To the left side of the graft materials in the bone defects, platelet-rich plasma (PRP) was added. The rats were sacrificed at one, three, and five weeks. Bone formation rate (BFR), remaining beta-TCP rate (RTR), beta-TCP absorption rate (TAR), whole amount of beta-TCP (WTCP), and total rate of BFR and RTR (TBR) were measured. Combined showed equivalent BFR to Allograft at five weeks, and showed higher RTR at one week and higher BFR at five weeks than TCP. Combined with PRP showed higher TAR than that without PRP at three weeks. Therefore, combination with allogenic bone showed reduced beta-TCP absorption, hence enhancing the role of beta-TCP in bone regeneration. These findings suggested that beta-TCP is a better scaffold for bone regeneration if its early absorption is reduced when used in combination with an osteogenic material.

DOI： 10.4012/dmj.28.153

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/eye.2008.152

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記述言語：英語  

DOI： 10.1016/j.humimm.2008.10.014

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語  

DOI： 10.1097/ICB.0b013e31817f2e2e

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: To describe vertical distraction osteogenesis of a scapular flap and removable lip support for oral rehabilitation after surgical creation of an ablative defect of the mandible. CASE REPORT: A 70-year-old man who was diagnosed with squamous cell carcinoma of the left lower gingiva underwent segmental mandibulectomy for tumor ablation and reconstruction with a scapular bone flap. To augment bone height of this flap, vertical distraction osteogenesis was performed. After denture fabrication, a removable lip support was placed between the implant-supported denture and the lower lip. RESULTS: The bone height of the scapular bone flap increased by 9 mm. Implants with adequate length could be placed in the distracted bone. The lip support was effective. Two years after masticatory loading, the implants remained stable. CONCLUSION: Vertical distraction osteogenesis of the scapular bone flap was suitable to facilitate postoperative functional and esthetic restoration after tumor resection. A removable lip support was also useful as a supplementary tool for oral rehabilitation.

DOI： 10.1016/j.tripleo.2008.05.048

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/j.1399-0039.2008.01111.x

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記述言語：英語  

Previously, we reported that phorbol 12-myristate 13-acetate (PMA)-activated protein kinase C (PKC) induced Rac1 activation in A172 glioblastoma cells. In this study, we investigated the mechanism of PMA-activated PKC-induced migration of glioblastoma cells by focusing on Rac1. PMA-induced formation of lamellipodia and focal complexes following migration were blocked by inhibiting Rac1 with small interfering RNA (siRNA), implicating Rac1 in PMA-induced glioblastoma cell migration. PMA-activated PKC induced phosphorylation of c-jun N-terminal kinase (JNK), one of the downstream effectors of Rac1. Immunohistochemical analysis showed that phosphorylated JNK was translocated to paxillin-containing focal complexes upon PMA stimulation and that Rac1 siRNA blocked these phenomena. These results suggest that phosphorylated JNK functions in cell migration and that JNK phosphorylation and translocation are mediated by Rac1. Furthermore, inhibition of Rac1 reduced phosphorylation of paxillin, a focal adhesion component and a downstream effector of JNK, at serine 178 (Ser178). Paxillin phosphorylation at this site has been shown to be involved in cell migration. Immunohistochemical analysis detected phosphorylation of paxillin (Ser178) in focal complexes upon PMA stimulation that was blocked by Rac1 siRNA. SP600125, a JNK inhibitor, also blocked PMA-induced phosphorylation of paxillin and aggregation of phosphorylated paxillin (Ser178) in focal complexes. In conclusion, paxillin is a critical downstream effector of Rac1 that may be involved in PMA-stimulated migration presumably by modulating the integrity of focal complex formation.

DOI： 10.3892/or_00000063

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Toll-like receptor 4 (TLR4) is a transmembrane receptor that mediates immune responses to exogenous and endogenous ligands and interacts with heat shock proteins, which are reportedly involved in normal tension glaucoma (NTG). This study was undertaken to investigate whether TLR4 polymorphisms are associated with NTG. METHODS: Two hundred fifty Japanese patients with NTG and 318 Japanese healthy control subjects were recruited. Eight single-nucleotide polymorphisms (SNPs) in the TLR4 gene were genotyped, and allelic and phenotypic diversity was assessed between cases and control subjects. RESULTS: Strong linkage disequilibrium was observed among all SNPs (D' >or= 0.85), which were located in one haplotype block. With respect to allelic diversity, the minor allele of three SNPs (rs10759930, rs1927914, and rs7037117) carried a significantly increased risk of NTG. With regard to genotypic diversity, individuals with the minor allele of six SNPs (rs10759930, rs1927914, rs1927911, rs12377632, rs2149356, and rs7037117) had a 1.47- to 1.65-fold increased risk of NTG. rs7037117, located in the 3'-untranslated region of TLR4, was most strongly associated with NTG, and when incorporated into a haplotype with rs10759930, the strongest association was detected (P = 0.0038, P(c) = 0.0095). CONCLUSIONS: Multiple SNPs in the TLR4 gene are associated with the risk of NTG. This finding suggests that the ligands and/or cytokines involved in the TLR4 signaling network may be risk factors for the development of NTG.

DOI： 10.1167/iovs.07-1575

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1136/bjo.2008.139980

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Corneal endothelial cell (CEC) transplantation should become clinically applicable in the near future. However, the immunologic changes after allo-CEC transplantation are poorly understood at present. We tried to establish a mouse model of allogeneic CEC transplantation for immunologic studies. METHODS: Benzalkonium chloride was injected into the anterior chamber of the eyes of recipient BALB/c mice to create bullous keratopathy. Full-thickness corneal transplantation was performed by using 4 types of corneas: BALB/c corneas (isograft group), BALB/c corneas denuded of CEC (no endothelium group), C3H/He mouse corneas (allograft group), and corneas reconstituted by seeding immortalized C3H/He mouse CECs onto BALB/c corneas denuded of endothelium (CEC allograft group). Eyes were observed with an operating microscope for 4 weeks after transplantation and were subjected to histologic examination and fluorescein microscopy. RESULTS: All corneal grafts were transparent in the isograft group (n = 12), whereas none of the grafts were clear by 4 weeks after transplantation in the no endothelium group (n = 13). Corneal grafts were transparent at 4 weeks in 75% of the CEC allograft group (n = 12). The histologic rejection rate was 0% in the CEC allograft group, which was significantly lower than in the allograft group (67%; n = 18; P < 0.01). CONCLUSIONS: We established a mouse allo-CEC transplantation model by using cultured cells. This model should be useful for studying the immunologic processes after CEC transplantation.

DOI： 10.1097/QAI.0b013e31815e722b

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/j.1399-0039.2008.01043.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.ijom.2008.01.002

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記述言語：英語  

DOI： 10.1136/ard.2007.079871

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1080/09273940802051100

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/ar2367

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記述言語：英語  

Toll-like receptors (TLRs) mediate signaling that triggers activation of the innate immune system, whereas heme oxygenase (HO)-1 (an inducible heme-degrading enzyme that is induced by various stresses) suppresses inflammatory responses. We investigated the interaction between TLR and HO-1 in an inflammatory disorder, namely Behçet&#039;s disease.Thirty-three patients with Behçet&#039;s disease and 30 healthy control individuals were included in the study. Expression levels of HO-1, TLR2 and TLR4 mRNA were semiquantitatively analyzed using a real-time PCR technique, and HO-1 protein level was determined by immunoblotting in peripheral blood mononuclear cells (PBMCs) and polymorphonuclear leukocytes. In some experiments, cells were stimulated with lipopolysaccharide or heat shock protein-60; these proteins are known to be ligands for TLR2 and 4.Levels of expression of HO-1 mRNA were significantly reduced in PBMCs from patients with active Behçet&#039;s disease, whereas those of TLR4, but not TLR2, were increased in PBMCs, regardless of disease activity. Moreover, HO-1 expression in PBMCs from patients with Behçet&#039;s disease was repressed in the presence of either lipopolysaccharide or heat shock

DOI： 10.1186/ar2367

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記述言語：英語  

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記述言語：英語  

Ten subjects were asked to pay attention to green or to red, when each visual stimulus was presented as two small squares, one green and the other red. They were instructed to push a button with the right hand, when the attended color was on the right side, and to push a button with the left hand, when the attended color was on the left side. The P1/N1 peak-to-peak amplitudes of visual event-related potentials were significantly higher when subjects focused attention on green rather than on red. We assume that the attended color had the effect of modulating the P1/N1 components.

DOI： 10.1016/j.neulet.2007.09.075

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

Purpose: Behcet&apos;s disease (BD) is known to be associated with HLA-B*51 in many different ethnic groups. Recently, the major histocompatibility complex class I chain-related gene A (MICA), located near the HLA-B gene, has been proposed as a candidate gene for BD susceptibility in several ethnic groups. To compare the relative contribution of MICA polymorphisms and HLA-B*51 to BD in different ethnic groups, we studied MICA polymorphisms in Turkish BD patients.
Methods: Thirty-three Turkish BD patients and 65 healthy controls were enrolled for analysis of polymorphisms in the extracellular domains of MICA.
Results: The phenotype frequencies of MICA*009 were significantly higher in BD patients (75.8%) than in controls (29.2%) (P = 0.000015). HLA-B*51 was also significantly more frequent in BD patients (81.8%) than in controls (29.2%) (P = 0.0000007). A strong association existed between MICA*009 and HLA-B*51. To assess the confounding effect of MICA*009 on HLA-B*51, we performed a stratification analysis that showed that BD was distinctly associated only with HLA-B*51.
Conclusion: Our results indicate that the major susceptibility gene for BD is HLA-B*51 and that the association between MICA*009 and BD arises from a strong linkage disequilibrium with HLA-B*51. However, we suggest that MICA*009 likely elicits an immune effect secondary to BD. Jpn J Ophthalmol 2007;51: 431-436 (c) Japanese Ophthalmological Society 2007.

DOI： 10.1007/s10384-007-0473-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/j.1399-0039.2007.00924.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語  

DOI： 10.1007/s00439-007-0388-1

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記述言語：日本語  

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記述言語：英語  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1080/09273940701346338

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記述言語：日本語  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s10384-006-0417-y

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記述言語：英語  

During the past decade, considerable efforts and resources have been devoted to elucidating the multiple genetic and environmental determinants responsible for hypertension and its associated cardiovascular diseases. The success of positional cloning, fine mapping, and linkage analysis based on whole-genome screening, however, has been limited in identifying multiple genetic determinants affecting diseases, suggesting that new research strategies for genome-wide typing may be helpful. Disease association (case-control) studies using microsatellite markers, distributed every 150 kb across the human genome, may have some advantages over linkage, candidate, and single nucleotide polymorphism typing methods in terms of statistical power and linkage disequilibrium for finding genomic regions harboring candidate disease genes, although it is not proven. We have carried out genome-wide mapping using 18,977 microsatellite markers in a Japanese population composed of 385 hypertensive patients and 385 normotensive control subjects. Pooled sample analysis was conducted in a 3-stage genomic screen of 3 independent case-control populations, and 54 markers were extracted from the original 18,977 microsatellite markers. As a final step, each single positive marker was confirmed by individual typing, and only 19 markers passed this test. We identified 19 allelic loci that were significantly different between the cases of essential hypertension and the controls.

DOI： 10.1161/01.HYP.0000257256.77680.02

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/jmv.20779

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1167/iovs.06-0991

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語  

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.

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記述言語：英語  

DOI： 10.1007/s00251-006-0155-9

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記述言語：英語  

DOI： 10.1016/j.jdermsci.2006.05.010

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記述言語：英語  

DOI： 10.1038/sj.jid.5700203

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/j.1399-0039.2006.00586.x

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To increase the degree of specificity for nomenclature in the current "Guidelines for Diagnosis of Ocular Sarcoidosis" published in 1990 by the Diffuse Pulmonary Disease Research Committee of Japan. SUBJECTS AND METHODS: We reviewed the records of patients with uveitis from the Uveitis Clinic in the Department of Ophthalmology at Yokohama City University. Subjects were selected from the records of uveitis patients with histologically proven sarcoidosis (78), and others with non-sarcoidosis uveitis (81). We examined the sensitivity and specificity of suspected characteristics of ocular sarcoidosis in the current "Guidelines for Diagnosis of Ocular Sarcoidosis". RESULTS: The definition specificity was improved by changing anterior uveitis to granulomatous anterior uveitis, and by simplifying to cloudy mass (snowball, string of pearls) from the previous diffused/cloudy mass vitreous opacity (snowball, string of pearls), and also by changing from retinal peripheral vasculitis (in many cases retinal periphlebitis, also at times retinal peripheral arteritis) to retinal periphlebitis. CONCLUSION: This newly proposed "Guidelines for Diagnosis of Ocular Sarcoidosis" gives a much clearer definition of sarcoidosis, as well as improved nomenclature for specific categories of ocular symptoms.

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記述言語：日本語   掲載種別：研究論文（国際会議プロシーディングス）  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We have developed a new high-throughput, high-resolution genotyping method for the detection of alleles at the human leukocyte antigen (HLA)-A, -B, -C, and -DRB1 loci by combining polymerase chain reaction (PCR) and sequence-specific oligonucleotide probes (SSOPs) protocols with the Luminex 100 xMAP flow cytometry dual-laser system to quantitate fluorescently labeled oligonucleotides attached to color-coded microbeads. In order to detect the HLA alleles with a frequency of more than 0.1% in the Japanese population, we created 48 oligonucleotide probes for the HLA-A locus, 61 for HLA-B, 34 for HLA-C, and 51 for HLA-DRB1. The accuracy of the PCR-SSOP-Luminex method was determined by comparing it to the nucleotide sequencing method after subcloning into the plasmid vector using 150 multinational control samples obtained from the International HLA DNA Exchange University of California Los Angeles. In addition, we performed the PCR-SSOP-Luminex method for HLA allele typing on DNA samples collected from 1,018 Japanese volunteers. Overall, the genotyping method exhibited an accuracy of 85.91% for HLA-A, 85.03% for HLA-B, 97.32% for HLA-C, and 90.67% for HLA-DRB1 using 150 control samples, and 100% for HLA-A and -C, 99.90% for HLA-B, and 99.95% for HLA-DRB1 in 1,018 Japanese samples. The PCR-SSOP-Luminex method provides a simple, accurate, and rapid approach toward multiplex genotyping of HLA alleles to the four-digit or higher level of resolution in the Japanese population. It takes only approximately 5 h from DNA extraction to the definition of HLA four-digit alleles at the HLA-A, HLA-B, HLA-C, and HLA-DRB1 loci for 96 samples when handled by a single typist.

DOI： 10.1007/s00251-005-0048-3

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記述言語：日本語   掲載種別：研究論文（国際会議プロシーディングス）  

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記述言語：英語  

DOI： 10.1097/01.ICL.0000152490.39831.4D

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記述言語：英語  

DOI： 10.1097/01.ICL.0000152491.96155.B4

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記述言語：英語  

DOI： 10.1089/jop.2005.21.157

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s00535-004-1560-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1080/09273940590928607

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記述言語：英語  

DOI： 10.1002/jmv.20295

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記述言語：英語  

DOI： 10.1016/j.exer.2004.09.010

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掲載種別：研究論文（学術雑誌）  

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記述言語：英語  

DOI： 10.1016/j.jdermsci.2004.07.011

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: We examined the effects of the immunosuppressive neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) on rat endotoxin-induced uveitis, and to measure the expression of inflammatory cytokines and chemokines with and without the alpha-MSH treatment over the course of the disease. METHODS: We injected Lewis rats once with Salmonella typhimurium lipopolysaccharide (LPS) to induce uveitis. The rats were given intravenous injections of 250, 500 or 1000 microg of alpha-MSH. The eyes were examined over the next 24 h for inflammation. Aqueous humor was collected 6, 12 and 24 h after endotoxin injections and the number of infiltrating cells were counted in anterior chamber. In addition, we assayed the concentration of protein, nitric oxide, TNF-alpha, IL-6, MCP-1 and MIP-2. RESULTS: Rats injected with alpha-MSH showed a significant decrease in the number of infiltrating cells in anterior chamber. Moreover, alpha-MSH-treated rats with endotoxin-induced uveitis (EIU) showed significantly lower concentrations of protein, nitric oxide, proinflammatory cytokines and chemokines in their aqueous humor. Even the early stages of EIU were suppressed by the injection of alpha-MSH. CONCLUSIONS: Our results demonstrate that the immunosuppressive neuropeptide alpha-MSH inhibits the early induction events of endotoxin-induced inflammation in the eye; therefore, suppresses the subsequent infiltration of cells and intraocular production of inflammatory cytokines and chemokines in eyes. alpha-MSH has a possibility of being a therapeutic strategy for anterior uveitis.

DOI： 10.1016/j.intimp.2004.04.011

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記述言語：英語  

DOI： 10.1016/j.jdermsci.2003.12.004

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記述言語：英語  

DOI： 10.1016/S1044-7431(03)00220-3

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記述言語：英語  

DOI： 10.1167/iovs.03-0246

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記述言語：英語  

DOI： 10.1007/s00018-003-2333-3

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記述言語：英語  

DOI： 10.1167/iovs.02-0822

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1034/j.1399-0039.2003.00014.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1034/j.1399-0039.2002.600506.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1034/j.1399-0039.2002.590207.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/S0895-4356(01)00388-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1034/j.1399-0039.2001.580306.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1034/j.1399-0039.2001.580201.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1034/j.1399-0039.2001.580202.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1101/gr.175801

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DOI： 10.1034/j.1399-0039.2001.057005457.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1006/geno.2000.6371

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記述言語：英語   掲載種別：研究論文（学術雑誌）