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=9 cd-vols= no-issue=8 article-no= start-page=1253 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220819 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Novel Lung Growth Strategy with Biological Therapy Targeting Airway Remodeling in Childhood Bronchial Asthma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Anti-inflammatory therapy, centered on inhaled steroids, suppresses airway inflammation in asthma, reduces asthma mortality and hospitalization rates, and achieves clinical remission in many pediatric patients. However, the spontaneous remission rate of childhood asthma in adulthood is not high, and airway inflammation and airway remodeling persist after remission of asthma symptoms. Childhood asthma impairs normal lung maturation, interferes with peak lung function in adolescence, reduces lung function in adulthood, and increases the risk of developing chronic obstructive pulmonary disease (COPD). Early suppression of airway inflammation in childhood and prevention of asthma exacerbations may improve lung maturation, leading to good lung function and prevention of adult COPD. Biological drugs that target T-helper 2 (Th2) cytokines are used in patients with severe pediatric asthma to reduce exacerbations and airway inflammation and improve respiratory function. They may also suppress airway remodeling in childhood and prevent respiratory deterioration in adulthood, reducing the risk of COPD and improving long-term prognosis. No studies have demonstrated a suppressive effect on airway remodeling in childhood severe asthma, and further clinical trials using airway imaging analysis are needed to ascertain the inhibitory effect of biological drugs on airway remodeling in severe childhood asthma. In this review, we describe the natural prognosis of lung function in childhood asthma and the risk of developing adult COPD, the pathophysiology of allergic airway inflammation and airway remodeling via Th2 cytokines, and the inhibitory effect of biological drugs on airway remodeling in childhood asthma. 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=IkedaMasanori en-aut-sei=Ikeda en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 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=Okayama University School of Medicine kn-affil= affil-num=3 en-affil=Department of Pediatrics, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=bronchial asthma kn-keyword=bronchial asthma en-keyword=chronic obstructive pulmonary disease kn-keyword=chronic obstructive pulmonary disease en-keyword=lung function trajectory kn-keyword=lung function trajectory en-keyword=type 2 inflammation kn-keyword=type 2 inflammation en-keyword=airway remodeling kn-keyword=airway remodeling en-keyword=omalizumab kn-keyword=omalizumab en-keyword=mepolizumab kn-keyword=mepolizumab en-keyword=benralizumab kn-keyword=benralizumab en-keyword=dupilumab kn-keyword=dupilumab END start-ver=1.4 cd-journal=joma no-vol=50 cd-vols= no-issue=1 article-no= start-page=03000605211070492 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220107 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Severe pediatric asthma with a poor response to omalizumab: a report of three cases and three-dimensional bronchial wall analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Omalizumab is used for the treatment of persistent severe allergic asthma in adults and children. However, some patients remain symptomatic even after omalizumab treatment. In bronchial asthma, chronic inflammation of the bronchial wall causes thickening of the airway wall, resulting from irreversible airway remodeling. Progression of airway remodeling causes airflow obstruction, leading to treatment resistance. We report three Japanese children with severe asthma who had a poor response to omalizumab treatment. They had a long period of inadequate management of asthma before initiating omalizumab. Even after omalizumab treatment, their symptoms persisted, and the parameters of spirometry tests did not improve. We hypothesized that omalizumab was less effective in these patients because airway wall remodeling had already progressed. We retrospectively evaluated the bronchial wall thickness using a three-dimensional bronchial wall analysis with chest computed tomography. The bronchial wall thickness was increased in these cases compared with six responders. Progressed airway wall thickness caused by airway remodeling may be associated with a poor response to omalizumab in children with severe asthma. 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=IkedaMasanori en-aut-sei=Ikeda en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KondoYoichi en-aut-sei=Kondo en-aut-mei=Yoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 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 Hospital kn-affil= affil-num=3 en-affil=Department of Pediatrics, Matsuyama Red Cross Hospital kn-affil= affil-num=4 en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Bronchial asthma kn-keyword=Bronchial asthma en-keyword=omalizumab kn-keyword=omalizumab en-keyword=bronchial wall thickness kn-keyword=bronchial wall thickness en-keyword=child kn-keyword=child en-keyword=computed tomography kn-keyword=computed tomography en-keyword=airway kn-keyword=airway END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=11 article-no= start-page=1067 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20211119 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Current Insights into Atopic March en-subtitle= kn-subtitle= en-abstract= kn-abstract=The incidence of allergic diseases is increasing, and research on their epidemiology, pathophysiology, and the prevention of onset is urgently needed. The onset of allergic disease begins in infancy with atopic dermatitis and food allergy and develops into allergic asthma and allergic rhinitis in childhood; the process is defined as "atopic march ". Atopic march is caused by multiple immunological pathways, including allergen exposure, environmental pollutants, skin barrier dysfunction, type 2 inflammation, and oxidative stress, which promote the progression of atopic march. Using recent evidence, herein, we explain the involvement of allergic inflammatory conditions and oxidative stress in the process of atopic march, its epidemiology, and methods for prevention of onset. 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=IkedaMasanori en-aut-sei=Ikeda en-aut-mei=Masanori 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=YorifujiTakashi en-aut-sei=Yorifuji en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 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=5 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 Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Epidemiology, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Epidemiology, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Pediatrics, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=atopic march kn-keyword=atopic march en-keyword=atopic dermatitis kn-keyword=atopic dermatitis en-keyword=food allergy kn-keyword=food allergy en-keyword=allergic asthma kn-keyword=allergic asthma en-keyword=allergic rhinitis kn-keyword=allergic rhinitis en-keyword=skin barrier dysfunction kn-keyword=skin barrier dysfunction en-keyword=alarmin kn-keyword=alarmin en-keyword=group 2 innate lymphoid cells kn-keyword=group 2 innate lymphoid cells en-keyword=type 2 inflammation kn-keyword=type 2 inflammation en-keyword=oxidative stress kn-keyword=oxidative stress en-keyword=specific biomarker kn-keyword=specific biomarker en-keyword=epidemiology kn-keyword=epidemiology en-keyword=phenotype kn-keyword=phenotype en-keyword=early intervention kn-keyword=early intervention en-keyword=emollient kn-keyword=emollient END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=10 article-no= start-page=100463 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202010 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evaluation of oral immunotherapy efficacy and safety by maintenance dose dependency: A multicenter randomized study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
Generally, oral immunotherapy (OIT) aims for daily administration. Recently, the efficacy of treatment with OIT at a low dose has been reported. However, the optimal dose and the evaluation of dose-dependent OIT outcome have not been described.
Methods
A multicenter, parallel, open-labeled, prospective, non-placebo controlled, randomized study enrolled 101 Japanese patients for treatment with OIT. We hypothesized that target dose OIT would induce short-term unresponsiveness (StU) earlier than reduced dose OIT. StU was defined as no response to 6200 mg whole egg, 3400 mg milk, and 2600 mg wheat protein, as evaluated by oral food challenge after 2-week ingestion cessation. To compare the two doses of OIT efficacy, the maximum ingestion doses during the maintenance phase of OIT were divided into 100%-dose or 25%-dose groups against their target StU dose, respectively. A total of 51 patients were assigned to the 100%-dose group [hen's egg (HE) = 26, cow's milk (CM) = 13, wheat = 12] and 50 to the 25%-dose group (HE = 25, CM = 13, wheat = 12). Primary outcome was established by comparing StU at 1 year. Secondary outcome was StU at 2 years and established by comparing allergic symptoms and immunological changes.
Results
The year 1 StU rates (%) for the 100%- and 25%-dose groups were 26.9 vs. 20.0 (HE), 7.7 vs. 15.4 (CM), and 50.0 vs. 16.7 (wheat), respectively. The year 2 StU rates were 30.8 vs. 36.0 (HE), 7.7 vs. 23.1 (CM), and 58.3 vs. 58.3 (wheat), respectively. There were no statistically significant differences in StU between years 1 and 2. The total allergic symptom rate in the 25%-dose group was lower than that in the 100%-dose group for egg, milk, and wheat. Antigen-specific IgE levels for egg-white, milk, and wheat decreased at 12 months.
Conclusions
Reduced maintenance dose of egg OIT showed similar therapeutic efficacy to the target dose. However, we were not able to clearly demonstrate the efficacy, particularly for milk and wheat. Reducing the maintenance dose for eggs, milk, and wheat may effectively lower the symptoms associated with their consumption compared to the target OIT dose. Furthermore, aggressive reduction of the maintenance dose might be important for milk and wheat, compared to the 25%-dose OIT. en-copyright= kn-copyright= en-aut-name=OguraKiyotake en-aut-sei=Ogura en-aut-mei=Kiyotake kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YanagidaNoriyuki en-aut-sei=Yanagida en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SatoSakura en-aut-sei=Sato en-aut-mei=Sakura kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ImaiTakanori en-aut-sei=Imai en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ItoKomei en-aut-sei=Ito en-aut-mei=Komei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KandoNaoyuki en-aut-sei=Kando en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 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=7 ORCID= en-aut-name=ShibataRumiko en-aut-sei=Shibata en-aut-mei=Rumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MurakamiYoko en-aut-sei=Murakami en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FujisawaTakao en-aut-sei=Fujisawa en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NagaoMizuho en-aut-sei=Nagao en-aut-mei=Mizuho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KawamotoNorio en-aut-sei=Kawamoto en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KondoNaomi en-aut-sei=Kondo en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=UrisuAtsuo en-aut-sei=Urisu en-aut-mei=Atsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TsugeIkuya en-aut-sei=Tsuge en-aut-mei=Ikuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KondoYasuto en-aut-sei=Kondo en-aut-mei=Yasuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=SugaiKazuko en-aut-sei=Sugai en-aut-mei=Kazuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=UchidaOsamu en-aut-sei=Uchida en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=UrashimaMitsuyoshi en-aut-sei=Urashima en-aut-mei=Mitsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=TaniguchiMasami en-aut-sei=Taniguchi en-aut-mei=Masami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=EbisawaMotohiro en-aut-sei=Ebisawa en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= affil-num=1 en-affil=Department of Pediatrics, National Hospital Organization, Sagamihara National Hospital kn-affil= affil-num=2 en-affil=Department of Pediatrics, National Hospital Organization, Sagamihara National Hospital kn-affil= affil-num=3 en-affil=Course of Allergy and Clinical Immunology, Juntendo University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Pediatrics, Showa University School of Medicine kn-affil= affil-num=5 en-affil=Department of Allergy, Aichi Children's Health and Medical Center kn-affil= affil-num=6 en-affil=Department of Allergy, Aichi Children's Health and Medical Center kn-affil= affil-num=7 en-affil=Department of Pediatric Acute Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Pediatrics, National Hospital Organization, Fukuoka National Hospital kn-affil= affil-num=9 en-affil=Department of Pediatrics, National Hospital Organization, Fukuoka National Hospital kn-affil= affil-num=10 en-affil=Institute for Clinical Research, National Hospital Organization, Mie National Hospital kn-affil= affil-num=11 en-affil=Institute for Clinical Research, National Hospital Organization, Mie National Hospital kn-affil= affil-num=12 en-affil=Department of Pediatrics, Graduate School of Medicine, Gifu University kn-affil= affil-num=13 en-affil=Department of Pediatrics, Graduate School of Medicine, Gifu University kn-affil= affil-num=14 en-affil=Department of Pediatrics, Fujita Health University, The Second Teaching Hospital kn-affil= affil-num=15 en-affil=Department of Pediatrics, Fujita Health University, The Second Teaching Hospital kn-affil= affil-num=16 en-affil=Department of Pediatrics, Fujita Health University, The Second Teaching Hospital kn-affil= affil-num=17 en-affil=Department of Pediatrics, National Hospital Organization, Yokohama Medical Center kn-affil= affil-num=18 en-affil=Department of Pediatrics, National Hospital Organization, Yokohama Medical Center kn-affil= affil-num=19 en-affil=Division of Molecular Epidemiology, The Jikei University School of Medicine kn-affil= affil-num=20 en-affil=Course of Allergy and Clinical Immunology, Juntendo University Graduate School of Medicine kn-affil= affil-num=21 en-affil=Course of Allergy and Clinical Immunology, Juntendo University Graduate School of Medicine kn-affil= en-keyword=Food hypersensitivity kn-keyword=Food hypersensitivity en-keyword=Immunotherapy kn-keyword=Immunotherapy en-keyword=Dose-response relationship kn-keyword=Dose-response relationship en-keyword=Desensitization kn-keyword=Desensitization END start-ver=1.4 cd-journal=joma no-vol=69 cd-vols= no-issue=3 article-no= start-page=356 end-page=369 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200404 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Japanese guidelines for atopic dermatitis 2020. en-subtitle= kn-subtitle= en-abstract= kn-abstract=Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion, which is frequently encountered in clinical practice. Skin barrier dysfunction leads to enhanced skin irritability to non-specific stimuli and epicutaneous sensitization. In the lesion site, a further inflammation-related reduction in skin barrier function, enhanced irritability and scratching-related stimuli deteriorate eczema, leading to vicious cycle of inflammation. The current strategies to treat AD in Japan from the perspective of evidence-based medicine consist of three primary measures: (i) the use of topical corticosteroids and tacrolimus ointment as the main treatment for the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling and advice about daily life. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice. en-copyright= kn-copyright= en-aut-name=KatohNorito en-aut-sei=Katoh en-aut-mei=Norito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OhyaYukihiro en-aut-sei=Ohya en-aut-mei=Yukihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=EbiharaTamotsu en-aut-sei=Ebihara en-aut-mei=Tamotsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KatayamaIchiro en-aut-sei=Katayama en-aut-mei=Ichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SaekiHidehisa en-aut-sei=Saeki en-aut-mei=Hidehisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShimojoNaoki en-aut-sei=Shimojo en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TanakaAkio en-aut-sei=Tanaka en-aut-mei=Akio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakaharaTakeshi en-aut-sei=Nakahara en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NagaoMizuho en-aut-sei=Nagao en-aut-mei=Mizuho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HideMichihiro en-aut-sei=Hide en-aut-mei=Michihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FujitaYuji en-aut-sei=Fujita en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FujisawaTakao en-aut-sei=Fujisawa en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=FutamuraMasaki en-aut-sei=Futamura en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MasudaKoji en-aut-sei=Masuda en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=MurotaHiroyuki en-aut-sei=Murota en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=Yamamoto-HanadaKiwako en-aut-sei=Yamamoto-Hanada en-aut-mei=Kiwako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= affil-num=1 en-affil=Department of Dermatology, Kyoto Prefectural University of Medicine Graduate School of Medical Science kn-affil= affil-num=2 en-affil=Allergy Center, National Center for Child Health and Development kn-affil= affil-num=3 en-affil=Department of Pediatric Acute Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Dermatology, Keio University School of Medicine kn-affil= affil-num=5 en-affil=Department of Dermatology, Graduate School of Medicine, Osaka University kn-affil= affil-num=6 en-affil=Department of Dermatology, Graduate School of Medicine, Nihon Medical School kn-affil= affil-num=7 en-affil=Department of Pediatrics, Graduate School of Medicine, Chiba University kn-affil= affil-num=8 en-affil=Department of Dermatology, Hiroshima University Graduate School of Biomedical Sciences kn-affil= affil-num=9 en-affil=Division of Skin Surface Sensing, Department of Dermatology, Graduate School of Medical Sciences, Kyushu University kn-affil= affil-num=10 en-affil=Division of Clinical Research, National Hospital Organization Mie National Hospital kn-affil= affil-num=11 en-affil=Department of Dermatology, Hiroshima University Graduate School of Biomedical Sciences kn-affil= affil-num=12 en-affil=Department of Pediatrics, Graduate School of Medicine, Chiba University kn-affil= affil-num=13 en-affil=Division of Allergy, National Hospital Organization Mie National Hospital kn-affil= affil-num=14 en-affil=Division of Pediatrics, National Hospital Organization Nagoya Medical Center kn-affil= affil-num=15 en-affil=Department of Dermatology, Kyoto Prefectural University of Medicine Graduate School of Medical Science kn-affil= affil-num=16 en-affil=Department of Dermatology, Nagasaki University Graduate School of Biomedical Sciences kn-affil= affil-num=17 en-affil=Allergy Center, National Center for Child Health and Development kn-affil= en-keyword=Atopic dermatitis kn-keyword=Atopic dermatitis en-keyword=Clinical practice guidelines kn-keyword=Clinical practice guidelines en-keyword=Eczema kn-keyword=Eczema en-keyword=Evidence-based medicine kn-keyword=Evidence-based medicine en-keyword=Treatment kn-keyword=Treatment 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=430 cd-vols= no-issue=2 article-no= start-page=592 end-page=597 dt-received= dt-revised= dt-accepted= dt-pub-year=2013 dt-pub=20130111 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=PML tumor suppressor protein is required for HCV production en-subtitle= kn-subtitle= en-abstract= kn-abstract=PML tumor suppressor protein, which forms discrete nuclear structures termed PML-nuclear bodies, has been associated with several cellular functions, including cell proliferation, apoptosis and antiviral defense. Recently, it was reported that the HCV core protein colocalizes with PML in PML-NBs and abrogates the PML function through interaction with PML. However, role(s) of PML in HCV life cycle is unknown. To test whether or not PML affects HCV life cycle, we examined the level of secreted HCV core and the infectivity of HCV in the culture supernatants as well as the level of HCV RNA in HuH-7-derived RSc cells, in which HCV-JFH1 can infect and efficiently replicate, stably expressing short hairpin RNA targeted to PML. In this context, the level of secreted HCV core and the infectivity in the supernatants from PML knockdown cells was remarkably reduced, whereas the level of HCV RNA in the PML knockdown cells was not significantly affected in spite of very effective knockdown of PML. In fact, we showed that PML is unrelated to HCV RNA replication using the subgenomic HCV-JFH1 replicon RNA, JRN/3-5B. Furthermore, the infectivity of HCV-like particle in the culture supernatants was significantly reduced in PML knockdown JRN/3-5B cells expressing core to NS2 coding region of HCV-JFH1 genome using the trans-packaging system. Finally, we also demonstrated that INI1 and DDX5, the PML-related proteins, are involved in HCV production. Taken together, these findings suggest that PML is required for HCV production. en-copyright= kn-copyright= en-aut-name=KurokiMisao en-aut-sei=Kuroki en-aut-mei=Misao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AriumiYasuo en-aut-sei=Ariumi en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HijikataMakoto en-aut-sei=Hijikata en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=DansakoHiromichi en-aut-sei=Dansako en-aut-mei=Hiromichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WakitaTakaji en-aut-sei=Wakita en-aut-mei=Takaji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShimotohnoKunitada en-aut-sei=Shimotohno en-aut-mei=Kunitada kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KatoNobuyuki en-aut-sei=Kato en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil= kn-affil=Okayama Univ, Dept Tumor Virol, Sch Med Dent & Pharmaceut Sci affil-num=2 en-affil= kn-affil=Okayama Univ, Dept Tumor Virol, Sch Med Dent & Pharmaceut Sci affil-num=3 en-affil= kn-affil=Kyoto Univ, Dept Viral Oncol, Inst Virus Res affil-num=4 en-affil= kn-affil=Okayama Univ, Dept Tumor Virol, Sch Med Dent & Pharmaceut Sci affil-num=5 en-affil= kn-affil=Okayama Univ, Dept Tumor Virol, Sch Med Dent & Pharmaceut Sci affil-num=6 en-affil= kn-affil=Natl Inst Infect Dis, Dept Virol 2 affil-num=7 en-affil= kn-affil=Natl Ctr Global Hlth & Med, Res Ctr Hepatitis & Immunol affil-num=8 en-affil= kn-affil=Okayama Univ, Dept Tumor Virol, Sch Med Dent & Pharmaceut Sci en-keyword=Hepatitis C virus kn-keyword=Hepatitis C virus en-keyword=PML kn-keyword=PML en-keyword=INI1 kn-keyword=INI1 en-keyword=DDX5 kn-keyword=DDX5 en-keyword=Tumor suppressor kn-keyword=Tumor suppressor en-keyword=Lipid droplet kn-keyword=Lipid droplet END start-ver=1.4 cd-journal=joma no-vol=409 cd-vols= no-issue=4 article-no= start-page=663 end-page=668 dt-received= dt-revised= dt-accepted= dt-pub-year=2011 dt-pub=20110617 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Plural assay systems derived from different cell lines and hepatitis C virus strains are required for the objective evaluation of anti-hepatitis C virus reagents en-subtitle= kn-subtitle= en-abstract= kn-abstract=Persistent hepatitis C virus (HCV) infection causes chronic liver diseases and is a global health problem. HuH-7 hepatoma-derived cells are widely used as the only cell-based HCV replication system for HCV research, including drug assays. Recently, using different hepatoma Li23-derived cells, we developed an HCV drug assay system (ORL8), in which the genome-length HCV RNA (O strain of genotype 1b) encoding renilla luciferase replicates efficiently. In this study, using the HuH-7-derived OR6 assay system that we developed previously and the ORL8 assay system, we evaluated 26 anti-HCV reagents, which other groups had reported as anti-HCV candidates using HuH-7-derived assay systems other than ORB. The results revealed that more than half of the reagents showed different anti-HCV activities from those in the previous studies, and that anti-HCV activities evaluated by the ORB and ORL8 assays were also frequently different. In further evaluation using the HuH-7-derived AH1R assay system, which was developed using the AH1 strain of genotype 1b, several reagents showed different anti-HCV activities in comparison with those evaluated by the OR6 and ORL8 assays. These results suggest that the different activities of anti-HCV reagents are caused by the differences in cell lines or HCV strains used for the development of assay systems. Therefore, we conclude that plural HCV assay systems developed using different cell lines or HCV strains are required for the objective evaluation of anti-HCV reagents. en-copyright= kn-copyright= en-aut-name=UedaYouki en-aut-sei=Ueda en-aut-mei=Youki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MoriKyoko en-aut-sei=Mori en-aut-mei=Kyoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AriumiYasuo en-aut-sei=Ariumi en-aut-mei=Yasuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 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=4 ORCID= en-aut-name=KatoNobuyuki en-aut-sei=Kato en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil= kn-affil=Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences affil-num=2 en-affil= kn-affil=Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences affil-num=3 en-affil= kn-affil=Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences affil-num=4 en-affil= kn-affil=Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences affil-num=5 en-affil= kn-affil=Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences en-keyword=HCV kn-keyword=HCV en-keyword=HCV RNA replication system kn-keyword=HCV RNA replication system en-keyword=Li23 cells kn-keyword=Li23 cells en-keyword=Reporter assay for anti-HCV reagents kn-keyword=Reporter assay for anti-HCV reagents END start-ver=1.4 cd-journal=joma no-vol=122 cd-vols= no-issue=1 article-no= start-page=9 end-page=16 dt-received= dt-revised= dt-accepted= dt-pub-year=2010 dt-pub=20100401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=The DNA damage sensors ataxia-telangiectasia mutated kinase and checkpoint kinase 2 are required for hepatitis C virus RNA replication kn-title=DNA ��Z��T�[ATM�L�i�[�[��Chk2�͂b�^�̉��E�C��X��RNA��ɕK�v�ł�� en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=AriumiYasuo en-aut-sei=Ariumi en-aut-mei=Yasuo kn-aut-name=�L�C�N�Y kn-aut-sei=�L�C kn-aut-mei=�N�Y aut-affil-num=1 ORCID= en-aut-name=KurokiMisao en-aut-sei=Kuroki en-aut-mei=Misao kn-aut-name=��ؔ�� kn-aut-sei=�� kn-aut-mei=�� aut-affil-num=2 ORCID= en-aut-name=DansakoHiromichi en-aut-sei=Dansako en-aut-mei=Hiromichi kn-aut-name=��_�� kn-aut-sei=�� kn-aut-mei=�_�� aut-affil-num=3 ORCID= en-aut-name=AbeKenichi en-aut-sei=Abe en-aut-mei=Kenichi kn-aut-name=�� kn-aut-sei=�� kn-aut-mei=�� aut-affil-num=4 ORCID= en-aut-name=IkedaMasanori en-aut-sei=Ikeda en-aut-mei=Masanori kn-aut-name=�r�c�� kn-aut-sei=�r�c kn-aut-mei=�� aut-affil-num=5 ORCID= en-aut-name=WakitaTakaji en-aut-sei=Wakita en-aut-mei=Takaji kn-aut-name=�e�c�� kn-aut-sei=�e�c kn-aut-mei=�� aut-affil-num=6 ORCID= en-aut-name=KatoNobuyuki en-aut-sei=Kato en-aut-mei=Nobuyuki kn-aut-name=��V kn-aut-sei=�� kn-aut-mei=��V aut-affil-num=7 ORCID= affil-num=1 en-affil= kn-affil=��R��w��w�@�㎕��w��ȁ@��ᇃE�C��X�w affil-num=2 en-affil= kn-affil=��R��w��w�@�㎕��w��ȁ@��ᇃE�C��X�w affil-num=3 en-affil= kn-affil=��R��w��w�@�㎕��w��ȁ@��ᇃE�C��X�w affil-num=4 en-affil= kn-affil=��R��w��w�@�㎕��w��ȁ@��ᇃE�C��X�w affil-num=5 en-affil= kn-affil=��R��w��w�@�㎕��w��ȁ@��ᇃE�C��X�w affil-num=6 en-affil= kn-affil=��ǌ��@�E�C��X�� affil-num=7 en-affil= kn-affil=��R��w��w�@�㎕��w��ȁ@��ᇃE�C��X�w en-keyword=HCV kn-keyword=HCV en-keyword=ATM kn-keyword=ATM en-keyword=Chk2 kn-keyword=Chk2 en-keyword=�h��q kn-keyword=�h��q en-keyword=DNA ��Z��T�[ kn-keyword=DNA ��Z��T�[ END start-ver=1.4 cd-journal=joma no-vol=120 cd-vols= no-issue=1 article-no= start-page=29 end-page=34 dt-received= dt-revised= dt-accepted= dt-pub-year=2008 dt-pub=20080501 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Statins inhibit hepatitis C virus RNA replication in human hepatoma cells kn-title=�|�{�̍זE��p��X�^�`��܂̂b�^�̉��E�C��X�}��ʂɂ�� en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=IkedaMasanori en-aut-sei=Ikeda en-aut-mei=Masanori kn-aut-name=�r�c�� kn-aut-sei=�r�c kn-aut-mei=�� aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=��R��w��w�@�㎕��w��ȁ@��q��w en-keyword=HCV kn-keyword=HCV en-keyword=��v��R�� kn-keyword=��v��R�� en-keyword=�X�^�`�� kn-keyword=�X�^�`�� en-keyword=HMG-CoA reductase kn-keyword=HMG-CoA reductase en-keyword=�Q��j��Q��j�� kn-keyword=�Q��j��Q��j�� END