Details of a Researcher - Hashiguchi, Akinori

Papers - Hashiguchi, Akinori

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飛彈, 麻里子, 阿部, 時也, 橋口, 明典, 粟津, 緑

発達腎研究会誌 25 ( 1 ) 30 - 33 2017.04

Joint Work, ISSN 0919-7532

子宮内劣悪環境によりネフロン数は減少する。尿細管、間質、微小血管密度、血管内皮機能も影響を受けている可能性がある。これらの変化が二次侵襲により明らかになるかを、成熟後の母体低栄養ラット仔に片側尿管結紮を行い検討した。胎生1日から出産まで飼料を対照の50%に制限した母体の仔ラット(NR)を6週齢で左尿管結紮し、7日後に体重、血圧を測定、血液、結紮側腎の尿を採取し、その後サクリファイス、病理学的検討を行った。結紮前のNRの体重は対照に比し有意に低く、収縮期血圧は高かった。結紮後、両者の体重の有意差はなくなったが、NRのみ血圧が有意に上昇した。閉塞腎の尿の生化学パラメーターは対照、NR間で差はみられなかった。BUNは結紮前後で対照では変化しなかったが、NRでは有意に増加した。結紮腎では尿細管壊死がNRにおいて著明に認められ、尿細管壊死面積の占有率は対照に比し有意に高値であった。また健側腎のcollagen面積の占有率は対照、NR間で差がなかったが、閉塞腎ではNRが有意に高値であった。CD31の染色性はNRと対照で差がなかった。閉塞腎の尿中nitric oxideはNR結紮腎の尿中で対照の1/10以下であった。eNOS発現は健側腎に比し閉塞腎で増加していたがその程度はNRでは対照に比し少なかった。以上、NRは尿管結紮による尿細管壊死、線維化の程度が強く、その原因として腎NO産生低下に起因する血管収縮による低酸素が考えられた。(著者抄録)

【IgA腎症update】組織学的予後分類日本分類とオックスフォード分類の比較

橋口, 明典

腎と透析 82 ( 4 ) 549 - 553 2017.04

Joint Work, ISSN 0385-2156

【計量(デジタル)病理学:画像の数値化から補助診断まで】定量的病理診断と病理形態学ルネサンス

橋口, 明典, 坂元, 亨宇

病理と臨床 35 ( 1 ) 32 - 40 2017.01

Joint Work, ISSN 0287-3745

Extraction of glomeruli in whole slide imaging of kidney biopsy specimens

Masahiro Ishikawa, Sumire Watanabe, Natsuki Honda, Naoki Kobayashi, Tokiya Abe, Akinori Hashiguchi, Michiie Sakamoto

Progress in Biomedical Optics and Imaging - Proceedings of SPIE (SPIE) 10140 2017

Joint Work, Accepted, ISSN 1605-7422

The pathological diagnosis of a transplanted kidney is made on Banff Classification in order to gain an accurate understanding of the condition of the kidney. This type of diagnosis is extremely difficult and, thus, a variety of methods for diagnosis, including diagnosis by electron microscope, are being considered at present. Quantification of the diagnostic information derived by image processing is required for such purposes. This study proposes an automatic extraction method for normal glomeruli for the purpose of quantifying Elastica Van Gieson(EVG)-stained pathology specimens. In addition, we provide a report on the package of methods that we have created for the extraction of the glomerulus in the cortex.

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肝線維化の定量と発癌リスク肝線維化定量技術

阿部, 時也, 波多野, まみ, 橋口, 明典, 坂元, 亨宇

The Liver Cancer Journal (メディカルレビュー社) 8 ( 2 ) 102 - 105 2016.12

Joint Work, ISSN 1883-9347

CiNii Research

【新規技術が創り出す肝疾患診療のスペクタクル】診断への応用デジタル画像解析技術を用いた肝病理組織の定量的評価

橋口, 明典, 坂元, 亨宇

肝・胆・膵 73 ( 5 ) 703 - 711 2016.11

Joint Work, ISSN 0389-4991

画像診断と病理肝線維化を診断肝線維化を病理学的に定量する

阿部, 時也, 波多野, まみ, 橋口, 明典, 坂元, 亨宇

肝臓クリニカルアップデート (医学図書出版) 2 ( 2 ) 203 - 207 2016.10

Joint Work, ISSN 2189-4469

CiNii Research

CD4+ T cell-dominant insulitis in acute-onset Type 1 diabetes mellitus associated with intraductal papillary mucinous adenoma

Yajima, K., Oikawa, Y., Ogata, K., Hashiguchi, A. and Shimada, A.

Endocr J (Japan Endocrine Society) 63 ( 9 ) 841 - 847 2016.09

Joint Work, ISSN 1348-4540

The loss of insulin-producing pancreatic beta-cells in Type 1 diabetes mellitus (DM) is presumably the result of a T cell-mediated process. In general, CD8+ T cells are the predominant lymphocytes in the insulitis lesions, and CD4+ T cell-dominant insulitis is very rare. We present a case of a 72-year-old woman presented with excessive thirst and a 3-month history of weight loss. She was in a state of ketosis, and her plasma glucose concentration and HbA1c value were elevated. Moreover, anti-islet autoantibodies were positive, thus acute-onset Type 1 DM was diagnosed. At the time of diagnosis, a tumour was detected in the pancreas; total pancreatectomy was carried out 2 months later. The pathological diagnosis was intraductal papillary mucinous adenoma. Immunohistochemical staining of a sample of non-tumorous pancreatic tissue revealed 13 insulitis lesions infiltrated by both CD4+ and CD8+ T cells, and interestingly there were more CD4+ T cells than CD8+ T cells in the lesions. Moreover, B cells and macrophages had also infiltrated the lesions, and these two cell frequencies were both positively correlated with CD4+ as well as CD8+ T cell frequencies. This was a rare case with acute-onset Type 1 DM characterized by CD4+ T cell-dominant insulitis. Proinflammatory cytokines that can promote beta-cell apoptosis or CD8+ T cell function are reported to be secreted from CD4+ T cells. Thus, together with B cells and macrophages, CD4+ T cell-associated immune responses may have, directly and/or indirectly, played a role in the pathogenesis of the Type 1 DM in this patient.

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腎移植1年後のeGFRとwhole slide imageを用いた移植腎生検組織における線維化定量値の比較検討

坂巻裕介, 阿部時也, 橋口明典, 香野日高, 篠田和伸, 森田伸也, 小西孝之助, 林晃一, 中川健

移植 ((一社)日本移植学会) 51 ( 総会臨時 ) 298 - 298 2016.09

Joint Work, ISSN 0578-7947

ステロイド治療が良好な結果をもたらしたIgA-dominant感染後糸球体腎炎の一例

菱川彰人, 徳山博文, 川口隆久, 橋口明典, 脇野修, 伊藤裕

日本腎臓学会誌 ((一社)日本腎臓学会) 58 ( 6 ) 813 - 813 2016.08

Joint Work, ISSN 0385-2385

【腎と透析診療指針2016】 (第11章)全身疾患に伴う腎疾患骨髄腫に伴う腎障害

坂巻, 裕介, 橋口, 明典, 香野, 日高, 中川, 健, 林, 晃一

腎と透析 80 ( 増刊 ) 366 - 369 2016.06

Joint Work, ISSN 0385-2156

【CKDの臨床検査と腎病理診断】 CKDの病理

橋口, 明典

臨床検査 (医学書院) 60 ( 6 ) 642 - 648 2016.06

Joint Work, ISSN 0485-1420

CiNii Research

たこつぼ型心筋症を合併した顕微鏡的多発血管炎の一例

坂巻裕介, 橋口明典, 香野日高, 林晃一, 中川健

日本透析医学会雑誌 ((一社)日本透析医学会) 49 ( Suppl.1 ) 584 - 584 2016.05

Joint Work, Accepted, ISSN 1340-3451

Pathological sub-analysis of a multicenter randomized controlled trial of tonsillectomy combined with steroid pulse therapy versus steroid pulse monotherapy in patients with immunoglobulin A nephropathy

Katafuchi, R., Kawamura, T., Joh, K., Hashiguchi, A., Hisano, S., Shimizu, A., Miyazaki, Y., Nagata, M., Matsuo, S. and Ig, A. nephropathy Study Group in Japan

Clin Exp Nephrol (Springer Tokyo) 20 ( 2 ) 244 - 52 2016.04

Joint Work, ISSN 1437-7799

BACKGROUND: The IgA nephropathy (IgAN) Study Group in Japan conducted a multicenter, randomized, controlled trial of tonsillectomy with steroid pulse therapy (TSP) versus steroid pulse monotherapy in patients with IgAN (UMIN Clinical Trial Registry Number; C000000384). The effects of therapies in relation to pathological severity were analyzed in this study. METHODS: The patients with IgAN, urinary protein 1.0-3.5 g/day, serum creatinine of 1.5 mg/dl or less were randomly assigned to receiving TSP (Group A) or steroid pulses alone (Group B). The primary endpoint was the disappearance of proteinuria and/or hematuria. Twenty-six biopsies in Group A and 33 in Group B were available. The histological grades (HG) according to the percentage of glomeruli with crescent or sclerosis and the Oxford classification were analyzed. RESULTS: The patients in Group A had a 4.32- to 12.1-fold greater benefit of disappearance of proteinuria and 3.61- to 8.17-fold greater benefit of clinical remission (disappearance of proteinuria and hematuria) than those in Group B in patients with HG2-3, acute lesions (cellular or fibrocellular crescent) affecting more than 5 % of glomeruli, chronic lesions (fibrous crescents or sclerosis) affecting more than 20 % and S1. In contrast, odds ratios for disappearance of proteinuria or clinical remission in Group A to Group B were not significant in patients with HG 1, acute lesion in 5 % or less of glomeruli, chronic lesion in 20 % or less and S0. The disappearance of hematuria showed no relation to pathological severity. CONCLUSION: TSP might be better employed according to the pathological severity.

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Automatic quantification of morphological features for hepatic trabeculae analysis in stained liver specimens

Ishikawa, M., Murakami, Y., Ahi, S. T., Yamaguchi, M., Kobayashi, N., Kiyuna, T., Yamashita, Y., Saito, A., Abe, T., Hashiguchi, A. and Sakamoto, M.

J Med Imaging (Bellingham) (SPIE) 3 ( 2 ) 027502 2016.04

Joint Work, ISSN 2329-4302

This paper proposes a digital image analysis method to support quantitative pathology by automatically segmenting the hepatocyte structure and quantifying its morphological features. To structurally analyze histopathological hepatic images, we isolate the trabeculae by extracting the sinusoids, fat droplets, and stromata. We then measure the morphological features of the extracted trabeculae, divide the image into cords, and calculate the feature values of the local cords. We propose a method of calculating the nuclear-cytoplasmic ratio, nuclear density, and number of layers using the local cords. Furthermore, we evaluate the effectiveness of the proposed method using surgical specimens. The proposed method was found to be an effective method for the quantification of the Edmondson grade.

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血栓性微小血管症と抗リン脂質抗体症候群を合併したループス腎炎の1例

坂巻, 裕介, 小西, 孝之助, 橋口, 明典, 冨田, 茂樹, 久保田, 英司, 伊藤, 裕, 林, 晃一

日本腎臓学会誌 58 ( 1 ) 45 - 54 2016.01

Joint Work, ISSN 0385-2385

症例は48歳、女性。21歳時に、顔面、四肢の紅斑および発熱を認め、全身性エリテマトーデス(systemic lupus erythematosus:SLE)と診断され、副腎皮質ステロイド(プレドニゾロン)が開始された。当院入院の13日前にかかりつけ医を受診し、SLEの再燃が疑われて当科紹介となった。当院入院時の血液検査では、汎血球減少症、低補体血症、腎機能障害、ループス抗凝固因子の陽性、検尿では血尿と高度の蛋白尿が認められた。ループス腎炎の活動性評価目的で腎生検を施行後、プレドニゾロンによる免疫抑制療法に加え、抗血小板療法、抗凝固療法を開始した。第22病日には、破砕赤血球の出現を伴う溶血性貧血、血小板減少、腎機能障害の進行が認められた。新鮮凍結血漿を置換液とした血漿交換療法を計10回施行し全身状態や血小板減少は改善したが、腎機能の改善はなく、第36病日には血液透析を導入した。腎生検病理所見は、半月体形成と管内増殖を呈する高度の増殖性腎炎に加え、糸球体係蹄腔内には粗大な血栓を認め、細動脈内腔には閉塞性の硝子様沈着が認められた。蛍光抗体法による染色では、係蹄壁に免疫グロブリンと補体の顆粒状沈着を認め、電子顕微鏡では、分節性に上皮下と基底膜内の高電子密度沈着物を認めたものの、明らかな内皮下沈着物はみられなかった。ループス腎炎では、ステロイドを中心とした免疫抑制療法が治療の主体となるが、APSや血栓性微小血管症を合併した場合、免疫抑制療法に加え、抗血小板療法、抗凝固療法、血漿交換療法を含めた集学的治療が必要となる。ループス腎炎の病態は不明な点が多いが、今回われわれは、TMAが腎障害の進行に関与した可能性が示唆されたループス腎炎の1例を経験したので報告する。(著者抄録)

Elastin Fiber Accumulation in Liver Correlates with the Development of Hepatocellular Carcinoma

Yasui, Y., Abe, T., Kurosaki, M., Higuchi, M., Komiyama, Y., Yoshida, T., Hayashi, T., Kuwabara, K., Takaura, K., Nakakuki, N., Takada, H., Tamaki, N., Suzuki, S., Nakanishi, H., Tsuchiya, K., Itakura, J., Takahashi, Y., Hashiguchi, A., Sakamoto, M. and Izumi, N.

PLoS One (PUBLIC LIBRARY SCIENCE) 11 ( 4 ) e0154558 2016

Joint Work, ISSN 1932-6203

BACKGROUND & AIMS: The fibrosis stage, which is evaluated by the distribution pattern of collagen fibers, is a major predictor for the development of hepatocellular carcinoma (HCC) for patients with hepatitis C. Meanwhile, the role of elastin fibers has not yet been elucidated. The present study was conducted to determine the significance of quantifying both collagen and elastin fibers. METHODS: We enrolled 189 consecutive patients with hepatitis C and advanced fibrosis. Using Elastica van Gieson-stained whole-slide images of pretreatment liver biopsies, collagen and elastin fibers were evaluated pixel by pixel (0.46 mum/pixel) using an automated computational method. Consequently, fiber amount and cumulative incidences of HCC within 3 years were analyzed. RESULTS: There was a significant correlation between collagen and elastin fibers, whereas variation in elastin fiber was greater than in collagen fiber. Both collagen fiber (p = 0.008) and elastin fiber (p < 0.001) were significantly correlated with F stage. In total, 30 patients developed HCC during follow-up. Patients who have higher elastin fiber (p = 0.002) in addition to higher collagen fiber (p = 0.05) showed significantly higher incidences of HCC. With regard to elastin fiber, this difference remained significant in F3 patients. Furthermore, for patients with a higher collagen fiber amount, higher elastin was a significant predictor for HCC development (p = 0.02). CONCLUSIONS: Computational analysis is a novel technique for quantification of fibers with the added value of conventional staging. Elastin fiber is a predictor for the development of HCC independently of collagen fiber and F stage.

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[Renal thrombotic microangiopathy and antiphospholipid syndrome nephropathy in a patient with lupus nephritis]

Sakamaki, Y., Konishi, K., Hashiguchi, A., Tomita, S., Kubota, E., Itoh, H. and Hayashi, K.

Nihon Jinzo Gakkai Shi 58 ( 1 ) 45 - 54 2016

ISSN 0385-2385

The patient was a 48-year-old Japanese woman diagnosed as having systemic lupus erythematosus at the age of 21 years when she presented with fever and an erythematous skin rash on her face and extremities. Prednisolone was initiated at that time. Thirteen days before admission to our hospital, she was referred to us by her family physician. Upon admission, blood tests showed pancytopenia, hypocomplementemia, and renal dysfunction, as well as the presence of lupus anticoagulant. Urinalysis showed abundant proteinuria and heavy microscopic hematuria. After performing a renal biopsy, we initiated immunosuppressive therapy and an anticoagulant. On the 22nd hospital day, microangiopathic hemolytic anemia appeared with the progression of thrombocytopenia and renal failure, and the patient subsequently underwent ten sessions of plasma exchange. After the commencement of the plasma exchange, her general condition improved. Her renal dysfunction, however, continued to progress, and hemodialysis was started on the 36th hospital day. The light microscopy showed severe endo- and extra-capillary proliferative glomerulonephritis with abundant crescents, and massive thrombi in the capillary lumen of the glomeruli. The arterioles contained occlusive hyaline materials. An immunofluorescence study showed granular staining of immunoglobulins and complements along the glomerular capillary wall. An electron microscopy examination revealed the presence of electron-dense deposits in the subepithelial and intramembranous areas of the glomeruli, but subendothelial deposits were absent. For cases with lupus nephritis (LN), immunosuppressive therapy based on corticosteroid remains the mainstay of treatment. However, immunosuppression alone may be insufficient when antiphospholipid antibody syndrome and thrombotic microangiopathy (TMA) are also present, and other treatment modalities including antiplatelet therapy, anticoagulation, and plasma exchange are likely to be necessary, as illustrated by the present case. Although the mechanism responsible for LN remains uncertain, we report a case of LN suggesting that TMA is associated with renal dysfunction.

Correction: Elastin Fiber Accumulation in Liver Correlates with the Development of Hepatocellular Carcinoma

PLoS One 11 ( 8 ) e0160133 2016

ISSN 1932-6203

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Renal thrombotic microangiopathy and antiphospholipid syndrome nephropathy in a patient with lupus nephritis

Yusuke Sakamaki, Konosuke Konishi, Akinori Hashiguchi, Shigeki Tomita, Eiji Kubota, Hiroshi Itoh, Koichi Hayashi

Japanese Journal of Nephrology (Japanese Society of Nephrology) 58 ( 1 ) 45 - 54 2016

Joint Work, ISSN 0385-2385

The patient was a 48-year-old Japanese woman diagnosed as having systemic lupus erythematosus at the age of 21 years when she presented with fever and an erythematous skin rash on her face and extremities. Prednisolonewas initiated at that time. Thirteen days before admission to our hospital, she was referred to us by her family physician. Upon admission, blood tests showed pancytopenia, hypocomplementemia, and renal dysfunction, as well as the presence of lupus anticoagulant. Urinalysis showed abundant proteinuria and heavy microscopic hematuria. After performing a renal biopsy, we initiated immunosuppressive therapy and an anticoagulant. On the 22nd hospital day, microangiopathic hemolytic anemia appeared with the progression of thrombocytopenia and renal failure, and the patient subsequently underwent ten sessions of plasma exchange. After the commencement of the plasma exchange, her general condition improved. Her renal dysfunction, however, continued to progress, and hemodialysis was started on the 36th hospital day. The light microscopy showed severe endo- And extra-capillary proliferative glomerulonephritis with abundant crescents, and massive thrombi in the capillary lumen of the glomeruli. The arterioles contained occlusive hyaline materials. An immunofluorescence study showed granular staining of immunoglobulins and complements along the glomerular capillary wall. An electron microscopy examination revealed the presence of electron-dense deposits in the subepithelial and intramembranous areas of the glomeruli, but subendo- Thelial deposits were absent. For cases with lupus nephritis (LN), immunosuppressive therapy based on corticosteroid remains the mainstay of treatment. However, immunosuppression alone may be insufficient when antiphos- pholipid antibody syndrome and thrombotic microangiopathy (TMA) are also present, and other treatment modalities including antiplatelet therapy, anticoagulation, and plasma exchange are likely to be necessary, as illustrated by the present case. Although the mechanism responsible for LN remains uncertain, we report a case of LN suggesting that TMA is associated with renal dysfunction.

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