start-ver=1.4 cd-journal=joma no-vol=156 cd-vols= no-issue=2 article-no= start-page=473 end-page=479.e1 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202508 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Dried blood spot proteome identifies subclinical interferon signature in neonates with type I interferonopathy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Type I interferonopathy is characterized by aberrant upregulation of type I interferon signaling. The mRNA interferon signature is a useful marker for activation of the interferon pathway and for diagnosis of type I interferonopathy; however, early diagnosis is challenging.
Objective: This study sought to identify the proteomic interferon signature in dried blood spot (DBS) samples. The aim was to evaluate the usefulness of the interferon signature for neonatal screening and to gain insight into presymptomatic state of neonates with inborn errors of immunity (IEIs).
Methods: DBS samples from healthy newborns/adults, patients with type I interferonopathy or other IEIs as well as from neonates with viral infections, including some samples obtained during the presymptomatic neonatal period, were examined by nontargeted proteome analyses. Expression of interferon-stimulated genes (ISGs) was evaluated and a DBS-interferon signature was defined. Differential expression/pathway analysis was also performed.
Results: The ISG products IFIT5, ISG15, and OAS2 were detected. Expression of IFIT5 and ISG15 was upregulated significantly in individuals with type I interferonopathy. We defined the sum of the z scores for these as the DBS-interferon signature, and found that patients with IEIs other than type I interferonopathy, such as chronic granulomatous disease (CGD), also showed significant elevation. Additionally, neonatal samples of type I interferonopathy and CGD patients showed high interferon signatures. Pathway analysis of neonatal CGD samples revealed upregulation of systemic lupus erythematosus–like pathways.
Conclusion: Upregulation of the interferon pathway exists already at birth—not only in neonates with type I interferonopathy but also in other IEIs, including CGD. en-copyright= kn-copyright= en-aut-name=NihiraHiroshi en-aut-sei=Nihira en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NakajimaDaisuke en-aut-sei=Nakajima en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=IzawaKazushi en-aut-sei=Izawa en-aut-mei=Kazushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawashimaYusuke en-aut-sei=Kawashima en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShibataHirofumi en-aut-sei=Shibata en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KonnoRyo en-aut-sei=Konno en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HigashiguchiMotoko en-aut-sei=Higashiguchi en-aut-mei=Motoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MiyamotoTakayuki en-aut-sei=Miyamoto en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=Nishitani-IsaMasahiko en-aut-sei=Nishitani-Isa en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HiejimaEitaro en-aut-sei=Hiejima en-aut-mei=Eitaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HondaYoshitaka en-aut-sei=Honda en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MatsubayashiTadashi en-aut-sei=Matsubayashi en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=IshiharaTakashi en-aut-sei=Ishihara en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YashiroMasato en-aut-sei=Yashiro en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IwataNaomi en-aut-sei=Iwata en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=OhwadaYoko en-aut-sei=Ohwada en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TomotakiSeiichi en-aut-sei=Tomotaki en-aut-mei=Seiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KawaiMasahiko en-aut-sei=Kawai en-aut-mei=Masahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=MurakamiKosaku en-aut-sei=Murakami en-aut-mei=Kosaku kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=OhnishiHidenori en-aut-sei=Ohnishi en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=IshimuraMasataka en-aut-sei=Ishimura en-aut-mei=Masataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=OkadaSatoshi en-aut-sei=Okada en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=YamashitaMotoi en-aut-sei=Yamashita en-aut-mei=Motoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=MorioTomohiro en-aut-sei=Morio en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=HoshinoAkihiro en-aut-sei=Hoshino en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=KaneganeHirokazu en-aut-sei=Kanegane en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=ImaiKohsuke en-aut-sei=Imai en-aut-mei=Kohsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=NakamuraYasuko en-aut-sei=Nakamura en-aut-mei=Yasuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=NonoyamaShigeaki en-aut-sei=Nonoyama en-aut-mei=Shigeaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=UchiyamaToru en-aut-sei=Uchiyama en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=OnoderaMasafumi en-aut-sei=Onodera en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=IshikawaTakashi en-aut-sei=Ishikawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=KawaiToshinao en-aut-sei=Kawai en-aut-mei=Toshinao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=TakitaJunko en-aut-sei=Takita en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= en-aut-name=NishikomoriRyuta en-aut-sei=Nishikomori en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=35 ORCID= en-aut-name=OharaOsamu en-aut-sei=Ohara en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=36 ORCID= en-aut-name=YasumiTakahiro en-aut-sei=Yasumi en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=37 ORCID= affil-num=1 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Applied Genomics, Kazusa DNA Research Institute kn-affil= affil-num=3 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Applied Genomics, Kazusa DNA Research Institute kn-affil= affil-num=5 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Applied Genomics, Kazusa DNA Research Institute kn-affil= affil-num=7 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Pediatrics, Seirei Hamamatsu General Hospital kn-affil= affil-num=13 en-affil=Department of Pediatrics, Nara Medical University kn-affil= affil-num=14 en-affil=Department of Pediatrics, Okayama University kn-affil= affil-num=15 en-affil=Department of Infection and Immunology, Aichi Children’s Health and Medical Center kn-affil= affil-num=16 en-affil=Department of Pediatrics, Dokkyo Medical University School of Medicine kn-affil= affil-num=17 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=18 en-affil=Department of Neonatology, Kyoto University Graduate School of Medicine kn-affil= affil-num=19 en-affil=Center for Cancer Immunotherapy and Immunobiology, Kyoto University Graduate School of Medicine kn-affil= affil-num=20 en-affil=Department of Pediatrics, Gifu University Graduate School of Medicine kn-affil= affil-num=21 en-affil=Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=22 en-affil=Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences kn-affil= affil-num=23 en-affil=Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (SCIENCE TOKYO) kn-affil= affil-num=24 en-affil=Laboratory of Immunology and Molecular Medicine, Advanced Research Initiative, Institute of Science Tokyo (SCIENCE TOKYO) kn-affil= affil-num=25 en-affil=Department of Child Health and Development, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (SCIENCE TOKYO) kn-affil= affil-num=26 en-affil=Department of Child Health and Development, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (SCIENCE TOKYO) kn-affil= affil-num=27 en-affil=Department of Pediatrics, National Defense Medical College kn-affil= affil-num=28 en-affil=Department of Pediatrics, National Defense Medical College kn-affil= affil-num=29 en-affil=Department of Pediatrics, National Defense Medical College kn-affil= affil-num=30 en-affil=Department of Human Genetics, National Center for Child Health and Development kn-affil= affil-num=31 en-affil=Department of Human Genetics, National Center for Child Health and Development kn-affil= affil-num=32 en-affil=Division of Immunology, National Center for Child Health and Development kn-affil= affil-num=33 en-affil=Division of Immunology, National Center for Child Health and Development kn-affil= affil-num=34 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= affil-num=35 en-affil=Department of Pediatrics and Child Health, Kurume University School of Medicine kn-affil= affil-num=36 en-affil=Department of Applied Genomics, Kazusa DNA Research Institute kn-affil= affil-num=37 en-affil=Department of Pediatrics, Kyoto University Graduate School of Medicine kn-affil= en-keyword=Inborn errors of immunity kn-keyword=Inborn errors of immunity en-keyword=interferonopathy kn-keyword=interferonopathy en-keyword=signature kn-keyword=signature en-keyword=proteome kn-keyword=proteome en-keyword=dried blood spot kn-keyword=dried blood spot en-keyword=CGD kn-keyword=CGD en-keyword=WAS kn-keyword=WAS en-keyword=newborn kn-keyword=newborn en-keyword=neonate kn-keyword=neonate END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=roaf042 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250603 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Recommendations for the treatment of juvenile idiopathic arthritis with oligoarthritis or polyarthritis from the 2024 update of the Japan College of Rheumatology Clinical Practice Guidelines for the management of rheumatoid arthritis including juvenile idiopathic arthritis with oligoarthritis or polyarthritis – secondary publication en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: To conduct systematic reviews (SRs) and develop clinical practice guidelines (CPGs) for managing juvenile idiopathic arthritis (JIA) with oligoarthritis or polyarthritis.
Methods: The Grading of Recommendations, Assessment, Development, and Evaluation methodology was employed to carry out SRs and formulate the CPGs. An expert panel, including patients, paediatric and nonpaediatric rheumatologists, guideline specialists, and patient representatives, used the Delphi method to discuss and agree on the recommendations.
Results: Six clinical questions (CQs) on the efficacy and safety of medical treatments were evaluated. These included CQ1 on methotrexate (MTX), CQ2 on non-MTX conventional synthetic disease-modifying antirheumatic drugs, CQ3 on glucocorticoids, CQ4 on tumour necrosis factor inhibitors, CQ5 on interleukin-6 inhibitors, and CQ6 on Janus kinase inhibitors. Two randomized controlled trials were identified for CQ1, three for CQ2, two for CQ3, eight for CQ4, two for CQ5, and two for CQ6. Based on these evaluations, three strong and three conditional recommendations were established. The CPGs have been endorsed by the Japan College of Rheumatology and the Pediatric Rheumatology Association of Japan.
Conclusions: The SRs provided the necessary evidence to develop the CPGs, which are intended to guide not only paediatric but also nonpaediatric rheumatologists, caregivers, patients, and their families in treatment decision-making. en-copyright= kn-copyright= en-aut-name=MiyamaeTakako en-aut-sei=Miyamae en-aut-mei=Takako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkamotoNami en-aut-sei=Okamoto en-aut-mei=Nami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=InoueYuzaburo en-aut-sei=Inoue en-aut-mei=Yuzaburo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KubotaTomohiro en-aut-sei=Kubota en-aut-mei=Tomohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=EbatoTakasuke en-aut-sei=Ebato en-aut-mei=Takasuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IrabuHitoshi en-aut-sei=Irabu en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KamedaHideto en-aut-sei=Kameda en-aut-mei=Hideto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KanekoYuko en-aut-sei=Kaneko en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KuboHiroshi en-aut-sei=Kubo en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MitsunagaKanako en-aut-sei=Mitsunaga en-aut-mei=Kanako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MoriMasaaki en-aut-sei=Mori en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NakajimaAyako en-aut-sei=Nakajima en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NishimuraKenichi en-aut-sei=Nishimura en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=OhkuboNaoaki en-aut-sei=Ohkubo en-aut-mei=Naoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=SatoTomomi en-aut-sei=Sato en-aut-mei=Tomomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=SugitaYuko en-aut-sei=Sugita en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=TakanashiSatoshi en-aut-sei=Takanashi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=TanakaTakayuki en-aut-sei=Tanaka en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=UmebayashiHiroaki en-aut-sei=Umebayashi en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=YashiroMasato en-aut-sei=Yashiro en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=YamanishiShingo en-aut-sei=Yamanishi en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=FusamaMie en-aut-sei=Fusama en-aut-mei=Mie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=HirataShintaro en-aut-sei=Hirata en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=KishimotoMitsumasa en-aut-sei=Kishimoto en-aut-mei=Mitsumasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=KohnoMasataka en-aut-sei=Kohno en-aut-mei=Masataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=KojimaMasayo en-aut-sei=Kojima en-aut-mei=Masayo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name=KojimaToshihisa en-aut-sei=Kojima en-aut-mei=Toshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=MorinobuAkio en-aut-sei=Morinobu en-aut-mei=Akio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= en-aut-name=SugiharaTakahiko en-aut-sei=Sugihara en-aut-mei=Takahiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=29 ORCID= en-aut-name=TanakaEiichi en-aut-sei=Tanaka en-aut-mei=Eiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=30 ORCID= en-aut-name=YajimaNobuyuki en-aut-sei=Yajima en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=31 ORCID= en-aut-name=YanaiRyo en-aut-sei=Yanai en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=32 ORCID= en-aut-name=KawahitoYutaka en-aut-sei=Kawahito en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=33 ORCID= en-aut-name=HarigaiMasayoshi en-aut-sei=Harigai en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=34 ORCID= affil-num=1 en-affil=Department of Pediatric Rheumatology, Institute of Rheumatology, Tokyo Women’s Medical University Hospital kn-affil= affil-num=2 en-affil=Department of Pediatrics, Osaka Rosai Hospital, Japan Organization of Occupational Health and Safety kn-affil= affil-num=3 en-affil=Department of General Medical Science, Graduate School of Medicine, Chiba University kn-affil= affil-num=4 en-affil=Department of Pediatrics, Kagoshima Prefectural Satsunan Hospital kn-affil= affil-num=5 en-affil=Department of Pediatrics, Kitasato University kn-affil= affil-num=6 en-affil=Department of Pediatrics and Development Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University kn-affil= affil-num=7 en-affil=Division of Rheumatology, Department of Internal Medicine, Toho University kn-affil= affil-num=8 en-affil=Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=9 en-affil=Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine kn-affil= affil-num=10 en-affil=Department of Allergy and Rheumatology, Chiba Children's Hospital kn-affil= affil-num=11 en-affil=Department of Lifetime Clinical Immunology, Tokyo Medical and Dental University kn-affil= affil-num=12 en-affil=Center for Rheumatic Diseases, Mie University Hospital kn-affil= affil-num=13 en-affil=Department of Pediatrics, Yokohama City University Graduate School of Medicine kn-affil= affil-num=14 en-affil=Iizuka Hospital kn-affil= affil-num=15 en-affil=Clinical Education Center For Physicians, Shiga University of Medical Science kn-affil= affil-num=16 en-affil=Department of Pediatrics, School of Medicine, Osaka Medical and Pharmaceutical University kn-affil= affil-num=17 en-affil=Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine kn-affil= affil-num=18 en-affil=Department of Pediatrics, Japanese Red Cross Otsu Hospital kn-affil= affil-num=19 en-affil=Department of Rheumatology and Infectious Diseases, Miyagi Children’s Hospital kn-affil= affil-num=20 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=21 en-affil=Department of Pediatrics, Nippon Medical School kn-affil= affil-num=22 en-affil=Health Sciences Department of Nursing, Kansai University of International Studies kn-affil= affil-num=23 en-affil=Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital kn-affil= affil-num=24 en-affil=Department of Nephrology and Rheumatology, Kyorin University School of Medicine kn-affil= affil-num=25 en-affil=Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine kn-affil= affil-num=26 en-affil=Graduate School of Medical Sciences, Nagoya City University kn-affil= affil-num=27 en-affil=Department of Orthopedic Surgery, National Hospital Organization Nagoya Medical Center kn-affil= affil-num=28 en-affil=Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University kn-affil= affil-num=29 en-affil=Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine kn-affil= affil-num=30 en-affil=Division of Rheumatology, Department of Internal Medicine, School of Medicine, Tokyo Women's Medical University kn-affil= affil-num=31 en-affil=Division of Rheumatology, Department of Medicine, Showa University School of Medicine kn-affil= affil-num=32 en-affil=Division of Rheumatology, Department of Medicine, Showa University School of Medicine kn-affil= affil-num=33 en-affil=Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine kn-affil= affil-num=34 en-affil=Division of Rheumatology, Department of Internal Medicine, School of Medicine, Tokyo Women's Medical University kn-affil= en-keyword=Clinical practice guidelines kn-keyword=Clinical practice guidelines en-keyword=baricitinib kn-keyword=baricitinib en-keyword=GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) kn-keyword=GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) en-keyword=juvenile idiopathic arthritis kn-keyword=juvenile idiopathic arthritis en-keyword=systematic review kn-keyword=systematic review END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=1 article-no= start-page=4 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250116 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Maternal smoking during infancy increases the risk of allergic diseases in children: a nationwide longitudinal survey in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background The incidence of allergic diseases has been increasing in Japan. In particular, a serious decline in the age of onset of allergic rhinitis has been observed. Passive smoking from parental smoking has a significant impact on children’s health; however, it is difficult to restrict smoking in the home. While various studies have previously reported on the relationship between passive smoking and the development of allergic diseases in children. However, there have been no reports on passive smoking and allergic diseases on a national scale.
Methods Using Japanese national longitudinal survey data (n = 38,444) for newborns born between May 10 and 24, 2010, we assessed parental smoking habits when their children were 6 months old and investigated the association with the development of allergic diseases until the age of 5.5 years. The risk ratios and 95% confidence intervals for the development of different allergic diseases were analyzed after adjusting for potential confounders using Poisson regression with a robust error variance.
Results The risk ratio for developing allergic rhinitis/allergic conjunctivitis (AR/AC) in children was significantly higher in the maternal smoking groups ( ≦ 10 cigarettes/day; RR 1.15, 95% CI 1.02–1.30; ≧11 cigarettes/day; RR 1.16, 95% CI 0.93–1.44). Furthermore, associations were found between the maternal smoking group in the presence of paternal smoking and the risk of developing bronchial asthma ( ≦ 10, RR 1.33 95% CI 1.17–1.52; ≧11, RR 1.71 95% CI 1.38–2.1), food allergy ( ≦ 10, RR 1.36 95% CI 1.12–1.63; ≧11, RR 1.25 95% CI 0.84–1.86), atopic dermatitis ( ≦ 10, RR 1.42 95% CI 1.22–1.66; ≧11, RR 1.6 95% CI 1.2–2.13), and AR/AC ( ≦ 10, RR 1.21 95% CI 1.07–1.36; ≧11, RR 1.35 95% CI 1.09–1.67).
Conclusions Maternal smoking during infancy increases the risk of developing AR/AC in children. Considering paternal smoking, maternal smoking further increased the risk of developing allergic diseases in children, suggesting that reducing parental smoking at home may reduce the risk of developing allergic diseases in children. en-copyright= kn-copyright= en-aut-name=ShigeharaKenji en-aut-sei=Shigehara en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoNaomi en-aut-sei=Matsumoto en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TsugeMitsuru en-aut-sei=Tsuge en-aut-mei=Mitsuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=UdaKazuhiro en-aut-sei=Uda en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SaitoYukie en-aut-sei=Saito en-aut-mei=Yukie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YashiroMasato en-aut-sei=Yashiro en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YorifujiTakashi en-aut-sei=Yorifuji en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IkedaMasanori en-aut-sei=Ikeda en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pediatric Acute Diseases, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Allergic rhinitis kn-keyword=Allergic rhinitis en-keyword=Bronchial asthma kn-keyword=Bronchial asthma en-keyword=Atopic dermatitis kn-keyword=Atopic dermatitis en-keyword=National cohort study kn-keyword=National cohort study en-keyword=Passive smoking kn-keyword=Passive smoking END start-ver=1.4 cd-journal=joma no-vol=19 cd-vols= no-issue=1 article-no= start-page=103 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231205 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Successful use of dupilumab for egg-induced eosinophilic gastroenteritis with duodenal ulcer: a pediatric case report and review of literature en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Non-esophageal eosinophilic gastrointestinal disorder (non-EoE-EGID) is a rare disease in which eosinophils infiltrate parts of the gastrointestinal tract other than the esophagus; however, the number of patients with non-EoE-EGID has been increasing in recent years. Owing to its chronic course with repeated relapses, it can lead to developmental delays due to malnutrition, especially in pediatric patients. No established treatment exists for non-EoE-EGID, necessitating long-term systemic corticosteroid administration. Although the efficacy of dupilumab, an anti-IL-4/13 receptor monoclonal antibody, for eosinophilic esophagitis, has been reported, only few reports have demonstrated its efficacy in non-EoE EGIDs.
Case presentation A 13-year-old boy developed non-EoE-EGID with duodenal ulcers, with chicken eggs as the trigger. He was successfully treated with an egg-free diet, proton pump inhibitors, and leukotriene receptor antagonists. However, at age 15, he developed worsening upper abdominal pain and difficulty eating. Blood analysis revealed eosinophilia; elevated erythrocyte sedimentation rate; and elevated levels of C-reactive protein, total immunoglobulin E, and thymic and activation-regulated chemokines. Upper gastrointestinal endoscopy revealed a duodenal ulcer with marked mucosal eosinophilic infiltration. Gastrointestinal symptoms persisted even after starting systemic steroids, making it difficult to reduce the steroid dose. Subcutaneous injection of dupilumab was initiated because of comorbid atopic dermatitis exacerbation. After 3 months, the gastrointestinal symptoms disappeared, and after 5 months, the duodenal ulcer disappeared and the eosinophil count decreased in the mucosa. Six months later, systemic steroids were discontinued, and the duodenal ulcer remained recurrence-free. The egg challenge test result was negative; therefore, the egg-free diet was discontinued. Blood eosinophil count and serum IL-5, IL-13, and eotaxin-3 levels decreased after dupilumab treatment. The serum levels of IL-5 and eotaxin-3 remained within normal ranges, although the blood eosinophil counts increased again after discontinuation of oral prednisolone.
Conclusions Suppression of IL-4R/IL-13R-mediated signaling by dupilumab may improve abdominal symptoms and endoscopic and histologic findings in patients with non-EoE-EGID, leading to the discontinuation of systemic steroid administration and tolerance of causative foods. en-copyright= kn-copyright= en-aut-name=TsugeMitsuru en-aut-sei=Tsuge en-aut-mei=Mitsuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShigeharaKenji en-aut-sei=Shigehara en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UdaKazuhiro en-aut-sei=Uda en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawanoSeiji en-aut-sei=Kawano en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SaitoYukie en-aut-sei=Saito en-aut-mei=Yukie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YashiroMasato en-aut-sei=Yashiro en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IkedaMasanori en-aut-sei=Ikeda en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Pediatric Acute Diseases, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Pediatrics, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Duodenal ulcer kn-keyword=Duodenal ulcer en-keyword=Dupilumab kn-keyword=Dupilumab en-keyword=Eosinophilic gastroenteritis kn-keyword=Eosinophilic gastroenteritis en-keyword=Eotaxin-3 kn-keyword=Eotaxin-3 en-keyword=Food allergy kn-keyword=Food allergy en-keyword=Interleukin-5 kn-keyword=Interleukin-5 en-keyword=Interleukin-13 kn-keyword=Interleukin-13 en-keyword=Non-esophageal eosinophilic gastrointestinal disorder kn-keyword=Non-esophageal eosinophilic gastrointestinal disorder END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue= article-no= start-page=1127053 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230328 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evaluation of the association of birth order and group childcare attendance with Kawasaki disease using data from a nationwide longitudinal survey en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Kawasaki disease (KD) is a form of pediatric systemic vasculitis. Although the etiology remains unclear, infections have been identified as possible triggers. Children with a later birth order and those who attend childcare are at a higher risk of infections due to exposure to pathogens from their older siblings and other childcare attendees. However, longitudinal studies exploring these associations are limited. Thus, we aimed to elucidate the relationship between birth order, group childcare attendance, and KD, using a nationwide longitudinal survey in Japan.
Methods: In total, 36,885 children born in Japan in 2010 were included. The survey used questionnaires to identify hospitalized cases of KD. We evaluated the relationship between birth order classification, group childcare attendance, and KD prevalence every year, from 6 to 66 months of age. For each outcome, odds ratios (ORs), and 95% confidence intervals (CIs) were estimated after adjusting for child factors, parental factors, and region of residence.
Results: Children with higher birth orders were more likely to be hospitalized with KD at 6-18 months of age (second child OR: 1.77, 95% CI: 1.25-2.51; third child OR: 1.70, 95% CI: 1.08-2.65). This trend was stronger for children who did not attend group childcare (second child OR: 2.51, 95% CI: 1.57-4.01; third child OR: 2.41, 95% CI: 1.30-4.43). An increased risk of KD hospitalization owing to the birth order was not observed in any age group for children in the childcare group.
Conclusions: Children with higher birth orders were at high risk for hospitalization due to KD at 6-18 months of age. The effect of birth order was more prominent among the children who did not attend group childcare. en-copyright= kn-copyright= en-aut-name=NambaTakahiro en-aut-sei=Namba en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakeuchiAkihito en-aut-sei=Takeuchi en-aut-mei=Akihito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsumotoNaomi en-aut-sei=Matsumoto en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsugeMitsuru en-aut-sei=Tsuge en-aut-mei=Mitsuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YashiroMasato en-aut-sei=Yashiro en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YorifujiTakashi en-aut-sei=Yorifuji en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neonatology, National Hospital Organization Okayama Medical Center kn-affil= affil-num=3 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Kawasaki disease (KD) kn-keyword=Kawasaki disease (KD) en-keyword=birth order kn-keyword=birth order en-keyword=group childcare kn-keyword=group childcare en-keyword=infectious diseases kn-keyword=infectious diseases en-keyword=vasculitis kn-keyword=vasculitis END start-ver=1.4 cd-journal=joma no-vol=22 cd-vols= no-issue=1 article-no= start-page=1517 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220809 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Correlation between national surveillance and search engine query data on respiratory syncytial virus infections in Japan en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background The respiratory syncytial virus (RSV) disease burden is significant, especially in infants and children with an underlying disease. Prophylaxis with palivizumab is recommended for these high-risk groups. Early recognition of a RSV epidemic is important for timely administration of palivizumab. We herein aimed to assess the correlation between national surveillance and Google Trends data pertaining to RSV infections in Japan. Methods The present, retrospective survey was performed between January 1, 2018 and November 14, 2021 and evaluated the correlation between national surveillance data and Google Trends data. Joinpoint regression was used to identify the points at which changes in trends occurred. Results A strong correlation was observed every study year (2018 [r = 0.87, p < 0.01], 2019 [r = 0.83, p < 0.01], 2020 [r = 0.83, p < 0.01], and 2021 [r = 0.96, p < 0.01]). The change-points in the Google Trends data indicating the start of the RSV epidemic were observed earlier than by sentinel surveillance in 2018 and 2021 and simultaneously with sentinel surveillance in 2019. No epidemic surge was observed in either the Google Trends or the surveillance data from 2020. Conclusions Our data suggested that Google Trends has the potential to enable the early identification of RSV epidemics. In countries without a national surveillance system, Google Trends may serve as an alternative early warning system. en-copyright= kn-copyright= en-aut-name=UdaKazuhiro en-aut-sei=Uda en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HagiyaHideharu en-aut-sei=Hagiya en-aut-mei=Hideharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YorifujiTakashi en-aut-sei=Yorifuji en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KoyamaToshihiro en-aut-sei=Koyama en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsugeMitsuru en-aut-sei=Tsuge en-aut-mei=Mitsuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YashiroMasato en-aut-sei=Yashiro en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=3 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pediatrics Acute Diseases, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical kn-affil= affil-num=6 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=RSV kn-keyword=RSV en-keyword=Surveillance kn-keyword=Surveillance en-keyword=Google Trends kn-keyword=Google Trends en-keyword=Epidemiology kn-keyword=Epidemiology END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=1 article-no= start-page=4819 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220321 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Thioredoxin interacting protein protects mice from fasting induced liver steatosis by activating ER stress and its downstream signaling pathways en-subtitle= kn-subtitle= en-abstract= kn-abstract=Under normal conditions, fasting results in decreased protein disulfide isomerase (PDI) activity and accumulation of unfolded proteins, leading to the subsequent activation of the unfolded protein response (UPR)/autophagy signaling pathway to eliminate damaged mitochondria. Fasting also induces upregulation of thioredoxin-interacting protein (TXNIP) expression and mice deficient of this protein (TXNIP-KO mice) was shown to develop severe hypoglycemia, hyperlipidemia and liver steatosis (LS). In the present study, we aimed to determine the role of TXNIP in fasting-induced LS by using male TXNIP-KO mice that developed LS without severe hypoglycemia. In TXNIP-KO mice, fasting induced severe microvesicular LS. Examinations by transmission electron microscopy revealed mitochondria with smaller size and deformities and the presence of few autophagosomes. The expression of beta-oxidation-associated genes remained at the same level and the level of LC3-II was low. PDI activity level stayed at the original level and the levels of p-IRE1 and X-box binding protein 1 spliced form (sXBP1) were lower. Interestingly, treatment of TXNIP-KO mice with bacitracin, a PDI inhibitor, restored the level of LC3-II after fasting. These results suggest that TXNIP regulates PDI activity and subsequent activation of the UPR/autophagy pathway and plays a protective role in fasting-induced LS. en-copyright= kn-copyright= en-aut-name=MiyaharaHiroyuki en-aut-sei=Miyahara en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HasegawaKosei en-aut-sei=Hasegawa en-aut-mei=Kosei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YashiroMasato en-aut-sei=Yashiro en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OharaToshiaki en-aut-sei=Ohara en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FujisawaMasayoshi en-aut-sei=Fujisawa en-aut-mei=Masayoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YoshimuraTeizo en-aut-sei=Yoshimura en-aut-mei=Teizo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=12 article-no= start-page=1433 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20211219 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Bilateral Optic Disc Swelling as a Plausible Common Ocular Sign of Autoinflammatory Diseases: Report of Three Patients with Blau Syndrome or Cryopyrin-Associated Periodic Syndrome en-subtitle= kn-subtitle= en-abstract= kn-abstract=The aim of this study is to describe bilateral optic disc swelling in three consecutive patients with Blau syndrome or cryopyrin-associated periodic syndrome at a single institution. Case 1 was a 30-year-old woman receiving 25 mg etanercept twice weekly who had been diagnosed as early-onset sarcoidosis by biopsy of skin rashes at 5 months old and genetically diagnosed with Blau syndrome with CARD15/NOD2 mutation (N670K) at 13 years old. At 10 years old, she began to have uveitis with optic disc swelling in both eyes, resulting in macular degeneration and optic disc atrophy at 17 years old only when etanercept was introduced. Case 2 was a 21-year-old man receiving adalimumab every 2 weeks who had been diagnosed as early-onset sarcoidosis by biopsy of skin rashes at 1.5 years old and genetically diagnosed as Blau syndrome with CARD15/NOD2 mutation (C495Y) at 5 years old. At 8 years old, around the time of adalimumab introduction, he began to show bilateral optic disc swelling which continued until the age of 16 years when the dose of adalimumab was increased. Case 3 was a 20-year-old woman receiving canakinumab every 8 weeks for systemic symptoms such as fever, headache, vomiting, and abdominal pain and later for sensorineural hearing disturbance on both sides. She had been diagnosed genetically with cryopyrin-associated periodic syndrome with NLRP3 mutation (Y859C) at 7 years old. At 5 years old, she was found to have bilateral optic disc swelling, which continued until the age of 10 years when she began receiving canakinumab (IL-1β inhibitor). Bilateral optic disc swelling might be tentatively designated as a plausible common ocular feature, if it occurred, in autoinflammatory diseases to pay more attention to ophthalmic complications in rare diseases. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YashiroMasato en-aut-sei=Yashiro en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamasakiOsamu en-aut-sei=Yamasaki en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MankiAkira en-aut-sei=Manki en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Department of Ophthalmology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Melanoma Center, Department of Dermatology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pediatrics, Okayama City Hospital kn-affil= en-keyword=autoinflammatory diseases kn-keyword=autoinflammatory diseases en-keyword=Blau syndrome kn-keyword=Blau syndrome en-keyword=Muckle-Wells syndrome kn-keyword=Muckle-Wells syndrome en-keyword=CINCA/NOMID syndrome kn-keyword=CINCA/NOMID syndrome en-keyword=cryopyrin-associated periodic syndromes kn-keyword=cryopyrin-associated periodic syndromes en-keyword=optic disc swelling (optic papillitis) kn-keyword=optic disc swelling (optic papillitis) END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=2021829 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Anti-high mobility group box 1 monoclonal antibody suppressed hyper-permeability and cytokine production in human pulmonary endothelial cells infected with influenza A virus en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective
High mobility group box-1 (HMGB1) has been reported to be involved in influenza A virus-induced acute respiratory distress syndrome (ARDS). We studied the efficacy of an anti-HMGB1 mAb using an in vitro model of TNF-α stimulation or influenza A virus infection in human pulmonary microvascular endothelial cells (HMVECs).

Methods
Vascular permeability of HMVECs was quantified using the Boyden chamber assay under tumor necrosis factor-α (TNF-α) stimulation or influenza A virus infection in the presence of anti-HMGB1 mAb or control mAb. The intracellular localization of HMGB1 was assessed by immunostaining. Extracellular cytokine concentrations and intracellular viral mRNA expression were quantified by the enzyme-linked immunosorbent assay and quantitative reverse transcription PCR, respectively.

Results
Vascular permeability was increased by TNF-α stimulation or influenza A infection; HMVECs became elongated and the intercellular gaps were extended. Anti-HMGB1 mAb suppressed both the increase in permeability and the cell morphology changes. Translocation of HMGB1 to the cytoplasm was observed in the non-infected cells. Although anti-HMGB1 mAb did not suppress viral replication, it did suppress cytokine production in HMVECs.

Conclusion
Anti-HMGB1 mAb might be an effective therapy for severe influenza ARDS. en-copyright= kn-copyright= en-aut-name=NambaTakahiro en-aut-sei=Namba en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsugeMitsuru en-aut-sei=Tsuge en-aut-mei=Mitsuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YashiroMasato en-aut-sei=Yashiro en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SaitoYukie en-aut-sei=Saito en-aut-mei=Yukie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=LiuKeyue en-aut-sei=Liu en-aut-mei=Keyue kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishiboriMasahiro en-aut-sei=Nishibori en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MorishimaTsuneo en-aut-sei=Morishima en-aut-mei=Tsuneo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Pediatrics, Aichi Medical University kn-affil= affil-num=8 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Influenza kn-keyword=Influenza en-keyword=Acute respiratory distress syndrome kn-keyword=Acute respiratory distress syndrome en-keyword=High mobility group box 1 kn-keyword=High mobility group box 1 en-keyword=Human pulmonary microvascular endothelial cell kn-keyword=Human pulmonary microvascular endothelial cell en-keyword=Cytokine kn-keyword=Cytokine en-keyword=Tumor necrosis factor-α kn-keyword=Tumor necrosis factor-α END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue= article-no= start-page=2324709620953283 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200829 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Long-Term Control of Macular Edema With Adalimumab After Cataract Surgery in a Japanese Child With Juvenile Idiopathic Arthritis: Case Report and Review of 26 Japanese Patients en-subtitle= kn-subtitle= en-abstract= kn-abstract=Juvenile idiopathic arthritis-associated uveitis is rare in the Japanese population. In this article, we report a child whose macular edema was controlled for years after cataract surgery with adalimumab, and reviewed 26 Japanese patients in the literature. In this case report, a 4-year-old boy developed band keratopathy, posterior iris synechiae, and complicated cataract in both eyes. Oral prednisolone prescribed at another hospital was discontinued due to high intraocular pressure in both eyes as a steroid responder. At the age of 5 years, he started oral methotrexate 8 mg weekly for recurrent bilateral iridocyclitis and then underwent lensectomy with core vitrectomy in both eyes. Planned intraocular lens implantation was cancelled at surgery because the anterior vitreous had severe inflammatory opacity with diffuse retinal edema in both eyes. Due to persistent macular edema in both eyes 5 months postoperatively, at the age of 6 years, he began to use adalimumab injection 20 mg every 2 weeks. The macular structure depicted by optical coherence tomography became normal in 2 months. At final visit at the age of 11 years, he had the best-corrected visual acuity of 0.8 in the right eye and 0.4 in the left eye, with adalimumab 40 mg every 2 weeks and methotrexate 8 mg weekly. In conclusion, macular edema persistent despite oral methotrexate after cataract surgery could be controlled for long term by adalimumab in a child with juvenile idiopathic arthritis. In the Japanese literature, only 26 additional cases with juvenile idiopathic arthritis-associated uveitis have been reported so far. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YashiroMasato en-aut-sei=Yashiro en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil= Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems kn-affil= affil-num=2 en-affil= kn-affil= en-keyword=juvenile idiopathic arthritis kn-keyword=juvenile idiopathic arthritis en-keyword=JIA kn-keyword=JIA en-keyword=macular edema kn-keyword=macular edema en-keyword=uveitis kn-keyword=uveitis en-keyword=adalimumab kn-keyword=adalimumab en-keyword=steroid responder kn-keyword=steroid responder en-keyword=cataract surgery kn-keyword=cataract surgery en-keyword=methotrexate kn-keyword=methotrexate en-keyword=literature review kn-keyword=literature review en-keyword=Japanese kn-keyword=Japanese END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue= article-no= start-page=2324709620953283 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200829 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Long-Term Control of Macular Edema With Adalimumab After Cataract Surgery in a Japanese Child With Juvenile Idiopathic Arthritis: Case Report and Review of 26 Japanese Patients en-subtitle= kn-subtitle= en-abstract= kn-abstract=Juvenile idiopathic arthritis–associated uveitis is rare in the Japanese population. In this article, we report a child whose macular edema was controlled for years after cataract surgery with adalimumab, and reviewed 26 Japanese patients in the literature. In this case report, a 4-year-old boy developed band keratopathy, posterior iris synechiae, and complicated cataract in both eyes. Oral prednisolone prescribed at another hospital was discontinued due to high intraocular pressure in both eyes as a steroid responder. At the age of 5 years, he started oral methotrexate 8 mg weekly for recurrent bilateral iridocyclitis and then underwent lensectomy with core vitrectomy in both eyes. Planned intraocular lens implantation was cancelled at surgery because the anterior vitreous had severe inflammatory opacity with diffuse retinal edema in both eyes. Due to persistent macular edema in both eyes 5 months postoperatively, at the age of 6 years, he began to use adalimumab injection 20 mg every 2 weeks. The macular structure depicted by optical coherence tomography became normal in 2 months. At final visit at the age of 11 years, he had the best-corrected visual acuity of 0.8 in the right eye and 0.4 in the left eye, with adalimumab 40 mg every 2 weeks and methotrexate 8 mg weekly. In conclusion, macular edema persistent despite oral methotrexate after cataract surgery could be controlled for long term by adalimumab in a child with juvenile idiopathic arthritis. In the Japanese literature, only 26 additional cases with juvenile idiopathic arthritis–associated uveitis have been reported so far. en-copyright= kn-copyright= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YashiroMasato en-aut-sei=Yashiro en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems kn-affil= affil-num=2 en-affil= Pediatrics, Okayama University Hospital and Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=juvenile idiopathic arthritis kn-keyword=juvenile idiopathic arthritis en-keyword=JIA kn-keyword=JIA en-keyword=macular edema kn-keyword=macular edema en-keyword=uveitis kn-keyword=uveitis en-keyword=adalimumab kn-keyword=adalimumab en-keyword=steroid responder kn-keyword=steroid responder en-keyword=cataract surgery kn-keyword=cataract surgery en-keyword=methotrexate kn-keyword=methotrexate en-keyword=literature review kn-keyword=literature review en-keyword=Japanese kn-keyword=Japanese END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=2380179 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2018 dt-pub=20180314 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Serum Procalcitonin Levels in Acute Encephalopathy with Biphasic Seizures and Late Reduced Diffusion en-subtitle= kn-subtitle= en-abstract= kn-abstract=Procalcitonin (PCT) is used as a biomarker in severe infections. Here, we retrospectively investigated levels of serum PCT, C-reactive protein (CRP), and inflammatory cytokines (IL-6, TNF-alpha, and IFN-gamma) in the second phase of patients with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD). Nine AESD pediatric patients (4 men, 5 women; AESD group) admitted to Okayama University Hospital from 2010 to 2016 were compared with 10 control patients with febrile seizures (FS) (3 men, 7 women; FS group). Mean PCT concentrations (ng/mL) in the AESD and FS groups were significantly different, at 9.8 +/- 6.7 and 0.8 +/- 0.9, respectively (p = 0 0006). CRP (mg/dL) were 0.79 +/- 0.89 and 1.4 +/- 1.0 (p = 0 94), respectively; IL-6 (pg/mL) were 449.7 +/- 705.0 and 118.3 +/- 145.4 (p = 0 20), respectively; TNF-alpha (pg/mL) were 18.6 +/- 12.5 and 16.6 +/- 6.0 (p = 0 67), respectively; and IFN-gamma (pg/mL) were 79.6 +/- 158.5 and 41.9 +/- 63.7 (p = 0 56), respectively. Ratios of PCT to CRP were 27.5 +/- 34.2 and 3.2 +/- 6.8 (p < 0 0001), respectively. The sensitivity and specificity in the diagnosis of AESD using a cutoff of PCT/CRP ratio of 1.0 were 79% and 100%, respectively. These results suggest that PCT and the PCT/CRP ratio are useful in auxiliary diagnosis of the second stage of AESD, and in AESD, PCT is likely to increase through a different mechanism. en-copyright= kn-copyright= en-aut-name=FujiiYosuke en-aut-sei=Fujii en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YashiroMasato en-aut-sei=Yashiro en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamadaMutsuko en-aut-sei=Yamada en-aut-mei=Mutsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KikkawaTomonobu en-aut-sei=Kikkawa en-aut-mei=Tomonobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NosakaNobuyuki en-aut-sei=Nosaka en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SaitoYukie en-aut-sei=Saito en-aut-mei=Yukie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TsukaharaKohei en-aut-sei=Tsukahara en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IkedaMasanori en-aut-sei=Ikeda en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MorishimaTsuneo en-aut-sei=Morishima en-aut-mei=Tsuneo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Pediatric Acute Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Emergency and Critical Care Medicine, Okayama University Graduate School of Medicine, Dentistry and kn-affil= affil-num=8 en-affil=Department of Pediatric Acute Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=74 cd-vols= no-issue=1 article-no= start-page=77 end-page=81 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202002 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Idiopathic Chondrolysis of the Hip Treated by Immunosuppressive Therapy and Arthroscopic Intervention en-subtitle= kn-subtitle= en-abstract= kn-abstract= Idiopathic chondrolysis of the hip (ICH), a very rare disorder of unknown etiology, occurs mainly in female adolescents. Characterized by pain, limp, stiffness and radiological narrowing joint space from the rapid destruction of the articular cartilage, ICH sometimes results in ankyloses. We present the case of a 10-year-old girl diagnosed with ICH based on arthroscopic inspection and synovium biopsy. The femoral deformity appeared gradually, like a cam-type femoroacetabular impingement. She was treated with intensive rehabilitation and immunosuppressive drug. We later performed an arthroscopic bumpectomy for residual symptoms. She achieved a favorable outcome as a 15-year-old at the latest follow-up. en-copyright= kn-copyright= en-aut-name=EndoHirosuke en-aut-sei=Endo en-aut-mei=Hirosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AkazawaHirofumi en-aut-sei=Akazawa en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YashiroMasato en-aut-sei=Yashiro en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamadaKazuki en-aut-sei=Yamada en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SankiTomoaki en-aut-sei=Sanki en-aut-mei=Tomoaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TetsunagaTomonori en-aut-sei=Tetsunaga en-aut-mei=Tomonori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishidaKeiichiro en-aut-sei=Nishida en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=FurumatsuTakayuki en-aut-sei=Furumatsu en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OzakiToshifumi en-aut-sei=Ozaki en-aut-mei=Toshifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Orthopaedic Surgery, Okayama Rosai Hospital kn-affil= affil-num=2 en-affil=Department of Orthopaedic Surgery, Asahigawaso Rehabilitation and Medical Center kn-affil= affil-num=3 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=idiopathic chondrolysis kn-keyword=idiopathic chondrolysis en-keyword=hip joint kn-keyword=hip joint en-keyword=medication kn-keyword=medication en-keyword=bump kn-keyword=bump en-keyword=arthroscopy kn-keyword=arthroscopy END start-ver=1.4 cd-journal=joma no-vol=71 cd-vols= no-issue=2 article-no= start-page=179 end-page=180 dt-received= dt-revised= dt-accepted= dt-pub-year=2017 dt-pub=201704 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Intracranial Pressure Monitoring for Pediatric Acute Encephalopathy en-subtitle= kn-subtitle= en-abstract= kn-abstract=Newly published clinical practice guidelines recommend intracranial pressure (ICP) monitoring in critical care for the management of pediatric acute encephalopathy (pAE), but the utility of ICP monitoring for pAE has been poorly studied. We recently performed direct ICP monitoring for two patients. We observed that although the direct ICP monitoring had clinical benefits with less body weight gain and no vasopressor use in both cases, this monitoring technique is still invasive. Future studies should determine the utility of non-invasive ICP monitoring systems in pAE to further improve the quality of intensive-care management. en-copyright= kn-copyright= en-aut-name=NosakaNobuyuki en-aut-sei=Nosaka en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsukaharaKohei en-aut-sei=Tsukahara en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KnaupEmily en-aut-sei=Knaup en-aut-mei=Emily kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YabuuchiToshihiko en-aut-sei=Yabuuchi en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KikkawaTomonobu en-aut-sei=Kikkawa en-aut-mei=Tomonobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiiYosuke en-aut-sei=Fujii en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YashiroMasato en-aut-sei=Yashiro en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YasuharaTakao en-aut-sei=Yasuhara en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OkadaAyumi en-aut-sei=Okada en-aut-mei=Ayumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=UgawaToyomu en-aut-sei=Ugawa en-aut-mei=Toyomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakaoAtsunori en-aut-sei=Nakao en-aut-mei=Atsunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=DateIsao en-aut-sei=Date en-aut-mei=Isao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Advanced Emergency and Critical Care Medical Center, Okayama University Hospital kn-affil= affil-num=2 en-affil=Advanced Emergency and Critical Care Medical Center, Okayama University Hospital kn-affil= affil-num=3 en-affil=Advanced Emergency and Critical Care Medical Center, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Neurological Surgery, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=10 en-affil=Advanced Emergency and Critical Care Center of Okayama University Hospital kn-affil= affil-num=11 en-affil=Advanced Emergency and Critical Care Medical Center, Okayama University Hospital kn-affil= affil-num=12 en-affil=Department of Pediatrics, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Neurological Surgery, Okayama University Hospital kn-affil= en-keyword=cerebral perfusion kn-keyword=cerebral perfusion en-keyword=encephalopathy kn-keyword=encephalopathy en-keyword=child kn-keyword=child en-keyword=intracranial pressure kn-keyword=intracranial pressure en-keyword=neurological intensive care kn-keyword=neurological intensive care END start-ver=1.4 cd-journal=joma no-vol=69 cd-vols= no-issue=5 article-no= start-page=279 end-page=290 dt-received= dt-revised= dt-accepted= dt-pub-year=2015 dt-pub=201510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Inhibitory Effects of Edaravone, a Free Radical Scavenger, on Cytokine-induced Hyperpermeability of Human Pulmonary Microvascular Endothelial Cells:A Comparison with Dexamethasone and Nitric Oxide Synthase Inhibitor en-subtitle= kn-subtitle= en-abstract= kn-abstract=Lung hyperpermeability affects the development of acute respiratory distress syndrome (ARDS), but therapeutic strategies for the control of microvascular permeability have not been established. We examined the effects of edaravone, dexamethasone, and N-monomethyl-L-arginine (L-NMMA) on permeability changes in human pulmonary microvascular endothelial cells (PMVEC) under a hypercytokinemic state. Human PMVEC were seeded in a Boyden chamber. After monolayer confluence was achieved, the culture media were replaced respectively by culture media containing edaravone, dexamethasone, and L-NMMA. After 24-h incubation, the monolayer was stimulated with tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Fluorescein-labeled dextran was added. Then the trans-human PMVEC leak was measured. Expressions of vascular endothelial-cadherin (VE-cadherin) and zonula occludens-1 protein (ZO-1) were evaluated using real-time quantitative polymerase chain reaction and immunofluorescence microscopy. The results showed that TNF-α＋IL-1β markedly increased pulmonary microvascular permeability. Pretreatment with edaravone, dexamethasone, or L-NMMA attenuated the hyperpermeability and inhibited the cytokine-induced reduction of VE-cadherin expression on immunofluorescence staining. Edaravone and dexamethasone increased the expression of ZO-1 at both the mRNA and protein levels. Edaravone and dexamethasone inhibited the permeability changes of human PMVEC, at least partly through an enhancement of VE-cadherin. Collectively, these results suggest a potential therapeutic approach for intervention in patients with ARDS. en-copyright= kn-copyright= en-aut-name=SaitoYukie en-aut-sei=Saito en-aut-mei=Yukie kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FujiiYousuke en-aut-sei=Fujii en-aut-mei=Yousuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YashiroMasato en-aut-sei=Yashiro en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsugeMitsuru en-aut-sei=Tsuge en-aut-mei=Mitsuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NosakaNobuyuki en-aut-sei=Nosaka en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamashitaNobuko en-aut-sei=Yamashita en-aut-mei=Nobuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamadaMutsuko en-aut-sei=Yamada en-aut-mei=Mutsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MorishimaTsuneo en-aut-sei=Morishima en-aut-mei=Tsuneo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil= kn-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=2 en-affil= kn-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=3 en-affil= kn-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=4 en-affil= kn-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=5 en-affil= kn-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=6 en-affil= kn-affil=Department of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=7 en-affil= kn-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=8 en-affil= kn-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=9 en-affil= kn-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences en-keyword=pulmonary microvascular endothelial cells kn-keyword=pulmonary microvascular endothelial cells en-keyword=permeability kn-keyword=permeability en-keyword=edaravone kn-keyword=edaravone en-keyword=vascular endothelial-cadherin kn-keyword=vascular endothelial-cadherin en-keyword=zonula occludens-1 protein kn-keyword=zonula occludens-1 protein END start-ver=1.4 cd-journal=joma no-vol=125 cd-vols= no-issue=2 article-no= start-page=109 end-page=112 dt-received= dt-revised= dt-accepted= dt-pub-year=2013 dt-pub=20130801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Therapeutic effects of redox-active protein thioredoxin(TRX)-1 in influenza-virus-induced pneumonia in mice kn-title=マウスインフルエンザ肺炎におけるレドックス制御蛋白チオレドキシン（TRX-1）の治療的効果 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=YashiroMasato en-aut-sei=Yashiro en-aut-mei=Masato kn-aut-name=八代将登 kn-aut-sei=八代 kn-aut-mei=将登 aut-affil-num=1 ORCID= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name=塚原宏一 kn-aut-sei=塚原 kn-aut-mei=宏一 aut-affil-num=2 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name=松川昭博 kn-aut-sei=松川 kn-aut-mei=昭博 aut-affil-num=3 ORCID= en-aut-name=YamadaMutsuko en-aut-sei=Yamada en-aut-mei=Mutsuko kn-aut-name=山田睦子 kn-aut-sei=山田 kn-aut-mei=睦子 aut-affil-num=4 ORCID= en-aut-name=FujiiYosuke en-aut-sei=Fujii en-aut-mei=Yosuke kn-aut-name=藤井洋輔 kn-aut-sei=藤井 kn-aut-mei=洋輔 aut-affil-num=5 ORCID= en-aut-name=NagaokaYoshiharu en-aut-sei=Nagaoka en-aut-mei=Yoshiharu kn-aut-name=長岡義晴 kn-aut-sei=長岡 kn-aut-mei=義晴 aut-affil-num=6 ORCID= en-aut-name=TsugeMitsuru en-aut-sei=Tsuge en-aut-mei=Mitsuru kn-aut-name=津下充 kn-aut-sei=津下 kn-aut-mei=充 aut-affil-num=7 ORCID= en-aut-name=YamashitaNobuko en-aut-sei=Yamashita en-aut-mei=Nobuko kn-aut-name=山下信子 kn-aut-sei=山下 kn-aut-mei=信子 aut-affil-num=8 ORCID= en-aut-name=ItoToshihiro en-aut-sei=Ito en-aut-mei=Toshihiro kn-aut-name=伊藤利洋 kn-aut-sei=伊藤 kn-aut-mei=利洋 aut-affil-num=9 ORCID= en-aut-name=YamadaMasao en-aut-sei=Yamada en-aut-mei=Masao kn-aut-name=山田雅夫 kn-aut-sei=山田 kn-aut-mei=雅夫 aut-affil-num=10 ORCID= en-aut-name=MasutaniHiroshi en-aut-sei=Masutani en-aut-mei=Hiroshi kn-aut-name=増谷弘 kn-aut-sei=増谷 kn-aut-mei=弘 aut-affil-num=11 ORCID= en-aut-name=YodoiJunji en-aut-sei=Yodoi en-aut-mei=Junji kn-aut-name=淀井淳司 kn-aut-sei=淀井 kn-aut-mei=淳司 aut-affil-num=12 ORCID= en-aut-name=MorishimaTsuneo en-aut-sei=Morishima en-aut-mei=Tsuneo kn-aut-name=森島恒雄 kn-aut-sei=森島 kn-aut-mei=恒雄 aut-affil-num=13 ORCID= affil-num=1 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 小児医科学 affil-num=2 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 小児医科学 affil-num=3 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 病理学（免疫病理） affil-num=4 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 小児医科学 affil-num=5 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 小児医科学 affil-num=6 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 小児医科学 affil-num=7 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 小児医科学 affil-num=8 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 小児医科学 affil-num=9 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 病理学（免疫病理） affil-num=10 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 病原ウイルス学 affil-num=11 en-affil= kn-affil=京都大学ウイルス研究所 生体応答学研究部門 affil-num=12 en-affil= kn-affil=京都大学ウイルス研究所 生体応答学研究部門 affil-num=13 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 小児医科学 en-keyword=acute lung injury kn-keyword=acute lung injury en-keyword=cytokine kn-keyword=cytokine en-keyword=influenza virus kn-keyword=influenza virus en-keyword=oxidative stress kn-keyword=oxidative stress en-keyword=thioredoxin-1 kn-keyword=thioredoxin-1 END start-ver=1.4 cd-journal=joma no-vol=52 cd-vols= no-issue=1 article-no= start-page=27 end-page=31 dt-received= dt-revised= dt-accepted= dt-pub-year=2013 dt-pub=20130101 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Thioredoxin-1 and oxidative stress status in pregnant women at early third trimester of pregnancy: relation to maternal and neonatal characteristics en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study examined the clinical and biological importance of thioredoxin-1, a redox-active defensive protein that controls multiple biological functions, in pregnant women. We measured serum concentrations of thioredoxin-1, total hydroperoxides, and redox potential in 60 pregnant women at the early third trimester: gestational age of 27-29 weeks. The thioredoxin-1 concentration (mean +/- SD) was 90 +/- 42 ng/ml. Total hydroperoxides was 471 +/- 105 U.CARR (1 U.CARR = 0.08 mg/dl H2O2). Redox potential was 2142 +/- 273 mu mol/l. The total hydroperoxides: redox potential ratio (oxidative stress index) was 0.23 +/- 0.08. Thioredoxin-1, total hydroperoxides, and oxidative stress index were higher and redox potential was lower than in blood of healthy adults. Total hydroperoxides and redox potential were mutually correlated significantly and negatively. Thioredoxin-1 correlated significantly and negatively and redox potential correlated significantly and positively with body weight and body mass index. Thioredoxin-1 and redox potential correlated significantly and positively with uric acid and albumin, respectively. Thioredoxin-1 and oxidative stress index correlated significantly and negatively and redox potential significantly and positively with neonatal birth weight. These results suggest that high concentrations of thioredoxin-1 are linked to high oxidative stress status in pregnant women and that neonatal birth weight is affected by the maternal oxidative condition during later pregnancy. en-copyright= kn-copyright= en-aut-name=NakatsukasaYoko en-aut-sei=Nakatsukasa en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TabuchiKazuhisa en-aut-sei=Tabuchi en-aut-mei=Kazuhisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TabuchiMasako en-aut-sei=Tabuchi en-aut-mei=Masako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MagamiTomoko en-aut-sei=Magami en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamadaMutsuko en-aut-sei=Yamada en-aut-mei=Mutsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=FujiiYosuke en-aut-sei=Fujii en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YashiroMasato en-aut-sei=Yashiro en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TsugeMitsuru en-aut-sei=Tsuge en-aut-mei=Mitsuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MorishimaTsuneo en-aut-sei=Morishima en-aut-mei=Tsuneo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil= kn-affil=Perineito Hahatokono Hosp Mothers & Children, Dept Pediat affil-num=2 en-affil= kn-affil=Okayama Univ, Dept Pediat, Grad Sch Med Dent & Pharmaceut Sci affil-num=3 en-affil= kn-affil=Perineito Hahatokono Hosp Mothers & Children, Dept Gynecol & Obstet affil-num=4 en-affil= kn-affil=Perineito Hahatokono Hosp Mothers & Children, Dept Gynecol & Obstet affil-num=5 en-affil= kn-affil=Perineito Hahatokono Hosp Mothers & Children, Dept Gynecol & Obstet affil-num=6 en-affil= kn-affil=Okayama Univ, Dept Pediat, Grad Sch Med Dent & Pharmaceut Sci affil-num=7 en-affil= kn-affil=Okayama Univ, Dept Pediat, Grad Sch Med Dent & Pharmaceut Sci affil-num=8 en-affil= kn-affil=Okayama Univ, Dept Pediat, Grad Sch Med Dent & Pharmaceut Sci affil-num=9 en-affil= kn-affil=Okayama Univ, Dept Pediat, Grad Sch Med Dent & Pharmaceut Sci affil-num=10 en-affil= kn-affil=Okayama Univ, Dept Pediat, Grad Sch Med Dent & Pharmaceut Sci en-keyword=later pregnancy kn-keyword=later pregnancy en-keyword=oxidative stress kn-keyword=oxidative stress en-keyword=redox potential kn-keyword=redox potential en-keyword=thioredoxin kn-keyword=thioredoxin en-keyword=total hydroperoxides kn-keyword=total hydroperoxides END start-ver=1.4 cd-journal=joma no-vol=41 cd-vols= no-issue=1 article-no= start-page=171 end-page=181 dt-received= dt-revised= dt-accepted= dt-pub-year=2013 dt-pub=201301 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Redox-Active Protein Thioredoxin-1 Administration Ameliorates Influenza A Virus (H1N1)-Induced Acute Lung Injury in Mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives: Influenza virus infections can cause severe acute lung injury leading to significant morbidity and mortality. Thioredoxin-1 is a redox-active defensive protein induced in response to stress conditions. Animal experiments have revealed that thioredoxin-1 has protective effects against various severe disorders. This study was undertaken to evaluate the protective effects of recombinant human thioredoxin-1 administration on influenza A virus (H1N1)-induced acute lung injury in mice. Design: Prospective animal trial. Setting: Research laboratory. Subjects: Nine-week-old male C57BL/6 mice inoculated with H1N1. Intervention: The mice were divided into a vehicle-treated group and recombinant human thioredoxin-1-treated group. For survival rate analysis, the vehicle or recombinant human thioredoxin-1 was administered intraperitoneally every second day from day -1 to day 13. For lung lavage and pathological analyses, vehicle or recombinant human thioredoxin-1 was administered intraperitoneally on days 1, 1, and 3. Measurements and Main Results: Lung lavage and pathological analyses were performed at 24, 72, and 120 hrs after inoculation. The recombinant human thioredoxin-1 treatment significantly improved the survival rate of H1N1-inoculated mice, although the treatment did not affect virus propagation in the lung. The treatment significantly attenuated the histological changes and neutrophil infiltration in the lung of H1N1-inoculated mice. The treatment significantly attenuated the production of tumor necrosis factor-a and chemokine (C-X-C motif) ligand 1 in the lung and oxidative stress enhancement, which were observed in H1N1-inoculated mice. H1N1 induced expressions of tumor necrosis factor-a and chemokine (C-X-C motif) ligand 1 in murine lung epithelial cells MLE-12, which were inhibited by the addition of recombinant human thioredoxin-1. The recombinant human thioredoxin-1 treatment started 30 mins after H1N1 inoculation also significantly improved the survival of the mice. Conclusions: Exogenous administration of recombinant human thioredoxin-1 significantly improved the survival rate and attenuated lung histological changes in the murine model of influenza pneumonia. The protective mechanism of thioredoxin-1 might be explained by its potent antioxidative and anti-inflammatory actions. Consequently, recombinant human thioredoxin-1 might be a possible pharmacological strategy for severe influenza virus infection in humans. (Crit Care Med 2013; 41:171-181) en-copyright= kn-copyright= en-aut-name=YashiroMasato en-aut-sei=Yashiro en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamadaMutsuko en-aut-sei=Yamada en-aut-mei=Mutsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FujiiYosuke en-aut-sei=Fujii en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NagaokaYoshiharu en-aut-sei=Nagaoka en-aut-mei=Yoshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TsugeMitsuru en-aut-sei=Tsuge en-aut-mei=Mitsuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamashitaNobuko en-aut-sei=Yamashita en-aut-mei=Nobuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ItoToshihiro en-aut-sei=Ito en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=YamadaMasao en-aut-sei=Yamada en-aut-mei=Masao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MasutaniHiroshi en-aut-sei=Masutani en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Pediat affil-num=2 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Pediat affil-num=3 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Pathol & Expt Med affil-num=4 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Pediat affil-num=5 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Pediat affil-num=6 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Pediat affil-num=7 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Pediat affil-num=8 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Pediat affil-num=9 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Pathol & Expt Med affil-num=10 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Virol affil-num=11 en-affil= kn-affil=Kyoto Univ, Inst Virus Res, Dept Biol Responses en-keyword=acute lung injury kn-keyword=acute lung injury en-keyword=cytokine kn-keyword=cytokine en-keyword=influenza virus kn-keyword=influenza virus en-keyword=mouse kn-keyword=mouse en-keyword=oxidative stress kn-keyword=oxidative stress en-keyword=thioredoxin-1 kn-keyword=thioredoxin-1 END