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論文
Wada, Taizo ; Toma, Tomoko ; Miyazawa, Hanae ; Koizumi, Eiko ; Shirahashi, Tetsujiro ; Matsuda, Yusuke ; Yachie, Akihiro ; 和田, 泰三 ; 東馬, 智子 ; 白橋, 徹志郎 ; 谷内江, 昭宏
出版情報: Journal of Dermatology.  45  pp.444-449,  2018-04-02.  日本皮膚科学会 = Japanese Dermatological Association / Blackwell Publishing Ltd
URL: http://hdl.handle.net/2297/00050510
概要: 金沢大学附属病院小児科<br />Epstein-Barr virus (EBV)-associated T- or natural killer (NK)-cell lymphoproliferative disease (LPD) is a heterogeneous group of disorders characterized by chronic proliferation of EBV-infected lymphocytes. Patients may present with severe skin manifestations, including hypersensitivity to mosquito bites (HMB) and hydroa vacciniforme (HV)-like eruption, which are characterized by blister formation and necrotic ulceration. Skin biopsy specimens show inflammatory reactions comprising EBV-infected lymphocytes. However, blister fluids have not been fully assessed in patients with this disease. Blister fluids were collected from three patients with EBV-associated LPD: two with HMB and one with HV. Immunophenotyping of blister lymphocytes and measurement of tumor necrosis factor (TNF)-α in blister fluids were performed. The patients with HMB and HV exhibited markedly increased percentages of NK and γδ T cells, respectively, in both peripheral blood and blister fluids. These NK and γδ T cells strongly expressed the activation marker human leukocyte antigen-DR and were considered to be cellular targets of EBV infections. TNF-α was highly elevated in all blister fluids. Severe local skin reactions of EBV-associated LPD may be associated with infiltrating EBV-infected lymphocytes and a high TNF-α concentration in blister fluids. © 2018 Japanese Dermatological Association.<br />Embargo Period 12 months 続きを見る
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Wada, Taizo ; Toma, Tomoko ; Matsuda, Yusuke ; Yachie, Akihiro ; Itami, Saori ; Taguchi, Y-h ; Murakami, Yoshiki
出版情報: Modern Rheumatology.  27  pp.1040-1046,  2017-11-02.  Japan College of Rheumatology / Taylor and Francis Ltd
URL: http://hdl.handle.net/2297/47073
概要: Objectives: Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by mutations in MEFV. Mutations in exon 10 are associated with typical FMF phenotypes, whereas the pathogenic role of variants in exons 2 and 3 remains uncertain. Recent evidence suggests that circulating microRNAs (miRNAs) are potentially useful biomarkers in several diseases. Therefore, their expression was assessed in FMF. Methods: The subjects were 24 patients with FMF who were between attacks: eight with exon 10 mutations (group A), eight with exon 3 mutations (group B), and eight without exon 3 or 10 mutations (group C). We also investigated eight cases of PFAPA as disease controls. Exosome-rich fractionated RNA was subjected to miRNA profiling by microarray. Results: Using the expression patterns of 26 miRNAs, we classified FMF (groups A, B, and C) and PFAPA with 78.1% accuracy. In FMF patients, groups A and B, A and C, and B and C were distinguished with 93.8, 87.5, and 100% accuracy using 24, 30, and 25 miRNA expression patterns, respectively. Conclusions: These findings suggest that expression patterns of circulating miRNAs differ among FMF subgroups based on MEFV mutations between FMF episodes. These patterns may serve as a useful biomarker for detecting subgroups of FMF. © 2017 Japan College of Rheumatology<br />Embargo Period 12 months 続きを見る
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Wada, Taizo ; Toma, Tomoko ; Miyazawa, Hanae ; Koizumi, Eiko ; Shirahashi, Tetsujiro ; Matsuda, Yusuke ; Yachie, Akihiro ; 和田, 泰三 ; 東馬, 智子 ; 小泉, 瑛子 ; 松田, 裕介 ; 谷内江, 昭宏
出版情報: Cytokine.  104  pp.143-146,  2018-04-01.  Academic Press / Elsevier
URL: http://hdl.handle.net/2297/00049794
概要: 金沢大学附属病院小児科<br />Background: Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by mutations in th e MEFV gene. Mutations in exon 10 are associated with typical FMF phenotypes, and patients with exon 10 mutations have higher serum levels of interleukin (IL)-18 both during attacks and afebrile phases, compared to those without exon 10 mutations. However, longitudinal changes of serum IL-18 in FMF have not been fully characterized. Methods: We serially evaluated serum levels of pro-inflammatory cytokines, including IL-18, in 12 patients with FMF carrying exon 10 mutations, all of whom showed typical FMF attacks. Results: Markedly high concentrations of IL-18 were observed in all patients at diagnosis (5099. ±. 6084. pg/mL). Serum IL-18 levels declined progressively after colchicine treatment in 7 patients (group A), whereas 5 patients showed continued elevation of circulating IL-18, despite declines in IL-6 and neopterin (group B). The mean follow-up times in the two groups were 4.7. ±. 3.2 and 4.8. ±. 1.5 years, respectively. The mean serum IL-18 level at the last hospital visit in group B was 4190. ±. 2610[U+202F]pg/mL. There were no differences in onset age, initial IL-18 levels, and colchicine doses between the groups. FMF attacks almost disappeared in both groups, but there were trends towards more frequent subtle symptoms such as abdominal discomfort in group B. Conclusions: Sustained elevation of serum IL-18 may suggest the presence of persistent subclinical inflammation. Therefore, longitudinal examination of serum IL-18 may contribute to better follow-up of FMF patients with exon 10 mutations. © 2017 Elsevier Ltd.<br />Embargo Period 12 moths 続きを見る
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Wada, Taizo ; Nishimura, Kashiku ; Kuroda, Mondo ; Asai, Erika ; Vu, Quang Van ; Toma, Tomoko ; Niida, Yo ; Yachie, Akihiro
出版情報: Brain and Development.  34  pp.376-379,  2012-05-01.  Elsevier / 日本小児神経学会Japanese Society of Child Neurology
URL: http://hdl.handle.net/2297/31375
概要: We report on a 9-year-old boy who presented with acute encephalopathy and hemophagocytic lymphohistiocytosis (HLH). The patient was referred to our hospital because of fever, seizures, and decreased consciousness. He showed moderately elevated levels of proinflammatory cytokines in the cerebrospinal fluid and plasma, and clonal expansion of highly activated CD8 + T cells in the peripheral blood. These CD8 + T cells were found to be larger cells that stained positive for T-cell receptor Vβ13.6, and decreased shortly after steroid therapy. Our findings suggest that his acute encephalopathy was likely a clinical manifestation of HLH, and that immunophenotypic analysis may be helpful for early recognition of HLH in such rare encephalopathy. © 2011 The Japanese Society of Child Neurology. 続きを見る
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Inoue, Mika ; Kasahara, Yoshihito ; Okajima, Michiko ; Wada, Taizo ; Toma, Tomoko ; Shimizu, Masaki ; Koizumi, Shoichi ; Yachie, Akihiro
出版情報: 金沢大学十全医学会雑誌 = Journal of the Jûzen Medical Society.  119  pp.154-163,  2010-12-01.  金沢大学十全医学会 = The Juzen Medical Society Kanazawa University
URL: http://hdl.handle.net/2297/27826
概要: 金沢大学医薬保健研究域保健学系<br />[Originals][原著]平成22年10月28日受付, 平成22年12月3日受理.
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Futagi, Toshihiko ; Kawahara, Ei ; Ohtake, Shigeki ; Nakashima, Hiroshi ; Yachie, Akihiro
出版情報: 金沢大学つるま保健学会誌 = Journal of the Tsuruma Health Science Society Kanazawa University.  33  pp.11-19,  2009-12-25.  金沢大学つるま保健学会 = the Tsuruma Health Science Society, Kanazawa University
URL: http://hdl.handle.net/2297/20306
概要: クルクミン(diferuloyl methane)は香辛料ターメリックの活性成分であり、試験管内あるいは生体内において強い抗酸化あるいは抗炎症作用などを示すとされているが、このような生物活性の機序としてheme oxygenase-1 (H O-1)の誘導を介することが知られている。本研究では、末梢血単球の炎症性サイトカイン産生におけるクルクミンの関与を明らかにすることを目的として行った。その結果、クルクミンは lipopolysaccharide により末梢血単核球に誘導されたTNF-alpha や IL-6の産生を抑制した一方で、IL-10やHO-1活性を有意に増強した。また、本研究で用いたクルクミンの濃度範囲において、アポトーシスや細胞死はほとんど認めなかったことから、クルクミンによる炎症性サイトカインの抑制効果はクルクミンの細胞毒性に起因したものではないといえた。さらに、HO活性抑制物質SnPP添加により単核球の培養後期においてクルクミンの抑制効果は部分的に解除された、このことから、クルクミンはHO-1産生を介した炎症性サイトカインの抑制を部分的に誘導することが示唆された一方で、他機序を介した単球への関与についても示唆された。クルクミンのような非細胞毒性を示す薬剤を利用することによる単球機能の調節は、さまざまな炎 症性疾患の新しい抗炎症治療への可能性が期待される。Curcumin (diferuloyl methane) is the active component of the spice turmeric and it exerts potent antioxidant and anti-inflammatory functions both in vitro and in vivo. The mechanism through which curcumin exhibits its biological functions is through induction of heme oxygenase-1 (HO-1). In the present study, we aimed to elucidate the direct effect of curcumin on inflammatory cytokine production by irculating monocytes. Curcumin inhibited lipopolysaccharide induced production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) by peripheral blood mononuclear cells, whereas it induced significant levels of interleukin-10 (IL-10) and HO-1. The inhibitory effect of curcumin was not via cytotoxicity of the reagent because there was no significant apoptosis or cell death induced over the range of concentrations used for the assay. The inhibitory effect of curcumin was partially abrogated by adding HO inhibitor SnPP at the late phase of the culture, indicating that the curcumin induced suppression of inflammatory cytokine is partly through production of HO-1. In addition, curcumin may act on monocytes through multiple mechanisms to regulate its inflammatory cytokine production. Modulation of monocyte functions by non-cytotoxic reagent such as curcumin may offer a novel anti-inflammatory therapeutics for the treatment of various inflammatory disorders. 続きを見る
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Takino, Yutaka ; Sasaki, Hisao ; Endo, Masamitsu ; Inazu, Akihiro ; Yachie, Akihiro
出版情報: 金沢大学つるま保健学会誌.  30  pp.1-9,  2006-02-28.  金沢大学つるま保健学会
URL: http://hdl.handle.net/2297/11819
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Ikawa, Yasuhiro ; Sugimoto, Naotoshi ; Koizumi, Shoichi ; Yachie, Akihiro ; Saikawa, Yutaka
出版情報: Journal of Pediatric Hematology/Oncology.  32  pp.41-10,  2010-01-01.  Lippincott, Williams & Wilkins
URL: http://hdl.handle.net/2297/21586
概要: 金沢大学医薬保健研究域<br />Infant acute lymphoblastic leukemia (ALL) displays distinct biologic and clinical features with a poor prognosis. The CD10-negative immunophenotype of infant ALL is a hallmark and provides a predictable signature of mixed-lineage leukemia (MLL) rearrangement. Although CD10 negativity reflects an earlier stage of B-cell development, complete IgH gene rearrangements (VDJH), found in almost half of the patients, show more mature IgH status. Discordance between immunophenotype and genotype of infant ALL suggests an aberrant process in immunophenotypic steps of differentiation or a secondary down-regulation of CD10 expression. In this study, CD10-negative infant ALL with MLL/AF4, CD10-positive infant ALL with germline MLL, CD10-positive pre-B ALL cell line, infant acute myeloid leukemia (AML; M5) with MLL/AF9 and pediatric AML (M2) with AML1/ETO were analyzed for VDJH status and methylation of CD10 gene promoters. Three of the 4 infant ALL samples showed complete rearrangements of the VDJH gene with productive joints. Bisulfite sequencing of CD10 type 1 and 2 promoters showed that more than 84% of the cytosine-phosphate-guanine (CpG) dinucleotides identified were methylated in all 3 CD10-negative infant ALL samples with MLL/AF4. The CpG dinucleotides distributed in the clusters of putative Sp1-binding sites and functionally active regulatory regions of the promoters were fully methylated. In contrast, none of the CpG dinucleotides were methylated in the CD10-positive ALL samples. Structural evidence of dense methylation in the CD10 gene promoter suggested that methylated transcription factor binding sites contribute to CD10 silencing as an epigenetic mechanism. © 2010 by Lippincott Williams & Wilkins. 続きを見る
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Wada, Taizo ; Yokoyama, Tadafumi ; Nakagawa, Hiroyasu ; Asai, Erika ; Taga, Akiko ; Sakakibara, Yasuhisa ; Shibata, Fumie ; Tone, Yumi ; Shimizu, Masaki ; Toma, Tomoko ; Yachie, Akihiro
出版情報: International Journal of Hematology.  90  pp.611-615,  2009-12-01.  The Japanese Society of Hematology = 日本血液学会
URL: http://hdl.handle.net/2297/20517
概要: 金沢大学医薬保健研究域医学系<br />In chronic active Epstein-Barr virus (EBV) infection (CAEBV), ectopic EBV infection has been describ ed in T or natural killer (NK) cells. NK cell-type infection (NK-CAEBV) is characterized by large granular lymphocytosis, high IgE levels and unusual reactions to mosquito bites, including severe local skin reactions, fever and liver dysfunction. However, the mechanisms underlying these reactions remain undetermined. Herein, we describe a patient with NK-CAEBV whose blister fluid after mosquito bites was analyzed. The patient exhibited significant increases in the percentage of CD56+ NK cells in the fluid compared with a simple mosquito allergy, in which the majority of infiltrated cells were CD203c+ cells, indicating basophils and/or mast cells. His fluid also contained CD203c+ cells, and his circulating basophils were activated by mosquito extracts in vitro. These results suggest that CD203c+ cells as well as NK cells may play pathogenic roles in the severe skin reactions to mosquito bites in NK-CAEBV. © 2009 The Japanese Society of Hematology.<br />出版者に照会中.2010年12月より全文公開予定. 続きを見る
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Shimizu, Masaki ; Tone, Yumi ; Toga, Akiko ; Yokoyama, Tadafumi ; Wada, Taizo ; Toma, Tomoko ; Yachie, Akihiro
出版情報: Rheumatology.  49  pp.2221-2223,  2010-06-04.  Oxford University Press (OUP)
URL: http://hdl.handle.net/2297/26270
概要: 金沢大学医薬保健研究域医学系