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-1�� 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-�� 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-�� (TNF-��) 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-�� 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-�� kn-keyword=Tumor necrosis factor-�� 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-�� (TNF-��) and interleukin-1�� (IL-1��). 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-��{IL-1�� 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=�}�E�X�C��t��G��U�x��ɂ��郌�h�b�N�X��`��`�I��h�L�V��iTRX-1�j�̎��ÓI�� 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=��㏫�o kn-aut-sei=�� kn-aut-mei=��o aut-affil-num=1 ORCID= en-aut-name=TsukaharaHirokazu en-aut-sei=Tsukahara en-aut-mei=Hirokazu kn-aut-name=�ˌ��G�� kn-aut-sei=�ˌ� kn-aut-mei=�G�� aut-affil-num=2 ORCID= en-aut-name=MatsukawaAkihiro en-aut-sei=Matsukawa en-aut-mei=Akihiro kn-aut-name=��쏺�� 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=�R�c�r�q kn-aut-sei=�R�c kn-aut-mei=�r�q aut-affil-num=4 ORCID= en-aut-name=FujiiYosuke en-aut-sei=Fujii en-aut-mei=Yosuke kn-aut-name=��m�� kn-aut-sei=�� kn-aut-mei=�m�� 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=�É��[ kn-aut-sei=�É� kn-aut-mei=�[ aut-affil-num=7 ORCID= en-aut-name=YamashitaNobuko en-aut-sei=Yamashita en-aut-mei=Nobuko kn-aut-name=�R��M�q kn-aut-sei=�R�� kn-aut-mei=�M�q aut-affil-num=8 ORCID= en-aut-name=ItoToshihiro en-aut-sei=Ito en-aut-mei=Toshihiro kn-aut-name=�ɓ��m kn-aut-sei=�ɓ� kn-aut-mei=��m aut-affil-num=9 ORCID= en-aut-name=YamadaMasao en-aut-sei=Yamada en-aut-mei=Masao kn-aut-name=�R�c��v kn-aut-sei=�R�c kn-aut-mei=��v aut-affil-num=10 ORCID= en-aut-name=MasutaniHiroshi en-aut-sei=Masutani en-aut-mei=Hiroshi kn-aut-name=��J�O kn-aut-sei=��J kn-aut-mei=�O aut-affil-num=11 ORCID= en-aut-name=YodoiJunji en-aut-sei=Yodoi en-aut-mei=Junji kn-aut-name=��~�i kn-aut-sei=�� kn-aut-mei=�~�i aut-affil-num=12 ORCID= en-aut-name=MorishimaTsuneo en-aut-sei=Morishima en-aut-mei=Tsuneo kn-aut-name=�X��P�Y kn-aut-sei=�X�� kn-aut-mei=�P�Y aut-affil-num=13 ORCID= affil-num=1 en-affil= kn-affil=��R��w��w�@�㎕��w�� Ȋw affil-num=2 en-affil= kn-affil=��R��w��w�@�㎕��w�� Ȋw affil-num=3 en-affil= kn-affil=��R��w��w�@�㎕��w�� a��w�i�Ɖu�a��j affil-num=4 en-affil= kn-affil=��R��w��w�@�㎕��w�� Ȋw affil-num=5 en-affil= kn-affil=��R��w��w�@�㎕��w�� Ȋw affil-num=6 en-affil= kn-affil=��R��w��w�@�㎕��w�� Ȋw affil-num=7 en-affil= kn-affil=��R��w��w�@�㎕��w�� Ȋw affil-num=8 en-affil= kn-affil=��R��w��w�@�㎕��w�� Ȋw affil-num=9 en-affil= kn-affil=��R��w��w�@�㎕��w�� a��w�i�Ɖu�a��j affil-num=10 en-affil= kn-affil=��R��w��w�@�㎕��w�� a��E�C��X�w affil-num=11 en-affil= kn-affil=��s��w�E�C��X�� ̉��w�� affil-num=12 en-affil= kn-affil=��s��w�E�C��X�� ̉��w�� affil-num=13 en-affil= kn-affil=��R��w��w�@�㎕��w�� Ȋw 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