Details of a Researcher - Hashiguchi, Akinori

Papers - Hashiguchi, Akinori

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Mesenchymal-epithelial transition of pancreatic cancer cells at perineural invasion sites is induced by Schwann cells

Fujii-Nishimura, Y., Yamazaki, K., Masugi, Y., Douguchi, J., Kurebayashi, Y., Kubota, N., Ojima, H., Kitago, M., Shinoda, M., Hashiguchi, A. and Sakamoto, M.

Pathol Int (Pathology International) 68 ( 4 ) 214 - 223 2018.04

Research paper (scientific journal), Joint Work, Accepted, ISSN 1440-1827

Epithelial-mesenchymal transition (EMT) promotes invasion and metastasis of pancreatic ductal adenocarcinoma (PDAC). However, the importance of its reverse process, mesenchymal-epithelial transition (MET), for PDAC remains unclear. We aimed to characterize the histological finding "focal differentiation" in PDAC at perineural invasion sites in the context of MET and to investigate the role of Schwann cells in inducing tumor MET. Tumor differentiation and immunohistochemical expressions of E-cadherin, SMAD3, and vimentin at perineural invasion sites were examined in 168 PDAC tissues. Four PDAC cell lines were co-cultured with Schwann cells to investigate cell morphology, motility, or EMT-related markers using immunocytochemistry and quantitative PCR. Of 168 tumors, 124 (74%) showed focal differentiation with enhanced E-cadherin membrane expression (P < 0.001) and decreased nuclear accumulation of SMAD3 (P < 0.001). Among 115 PDACs harboring grade 1/2 tumor, tumors with focal differentiation showed worse survival compared to those without focal differentiation (P = 0.019). PDAC cells co-cultured with Schwann cells demonstrated a sheet-like appearance, increased E-cadherin expression, decreased expressions of SMAD3 and vimentin, and reduced cell motility. In conclusion, MET-like change is induced by Schwann cells, suggesting that Schwann cells contribute to PDAC colonization in pancreatic nerves through activating the MET machinery inside tumor cells in the pancreatic tumor microenvironment.

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IgA腎症組織学的重症度分類A/C亜型の有用性の検証厚労省分科会前向き研究847症例の解析

城謙輔, 橋口明典, 清水章, 久野敏, 片渕律子, 中里毅, 川村哲也

日本腎臓学会誌 ((一社)日本腎臓学会) 60 ( 3 ) 364 - 364 2018.04

Research paper (scientific journal), Joint Work, Accepted, ISSN 0385-2385

C3腎症の視点から膜性増殖性糸球体腎炎(MPGN)の再検討 MPGN I型とIII型-2nd formは同一疾患か?

佐藤直実, 城謙輔, 中村保宏, 谷内真司, 橋口明典, 高木孝士, 笹野公伸

日本病理学会会誌 ((一社)日本病理学会) 107 ( 1 ) 448 - 448 2018.04

Research paper (scientific journal), Joint Work, Accepted, ISSN 0300-9181

IgA腎症における病理所見と治療反応性の検討 IgA腎症の腎病理所見と予後の関連に関する前向き多施設共同研究

片渕律子, 川村哲也, 橋口明典, 久野敏, 清水章, 城謙輔

日本腎臓学会誌 ((一社)日本腎臓学会) 60 ( 3 ) 364 - 364 2018.04

Research paper (scientific journal), Joint Work, Accepted, ISSN 0385-2385

【病理診断の新潮流】発症機序を考慮した糸球体疾患の分類

橋口, 明典

腎臓内科・泌尿器科 ((有)科学評論社) 7 ( 3 ) 201 - 205 2018.03

Research paper (scientific journal), Joint Work, Accepted, ISSN 2188-9147

Quantitative assessment of liver fibrosis reveals a nonlinear association with fibrosis stage in nonalcoholic fatty liver disease

Masugi, Y., Abe, T., Tsujikawa, H., Effendi, K., Hashiguchi, A., Abe, M., Imai, Y., Hino, K., Hige, S., Kawanaka, M., Yamada, G., Kage, M., Korenaga, M., Hiasa, Y., Mizokami, M. and Sakamoto, M.

Hepatol Commun (Hepatology Communications) 2 ( 1 ) 58 - 68 2018.01

Research paper (scientific journal), Joint Work, Accepted, ISSN 2471-254X

Accurate staging of liver fibrosis is crucial to guide therapeutic decisions for patients with nonalcoholic fatty liver disease (NAFLD). Digital image analysis has emerged as a promising tool for quantitative assessment of fibrosis in chronic liver diseases. We sought to determine the relationship of histologic fibrosis stage with fiber amounts quantified in liver biopsy specimens for the better understanding of NAFLD progression. We measured area ratios of collagen and elastin fibers in Elastica van Gieson-stained biopsy tissues from 289 patients with NAFLD from four hospitals using an automated computational method and examined their correlations with Brunt's fibrosis stage. As a secondary analysis, we performed multivariable logistic regression analysis to assess the associations of the combined area ratios of collagen and elastin with noninvasive fibrosis markers. The combined fiber area ratios correlated strongly with Brunt's stage (Spearman correlation coefficient, 0.78; P < 0.0001), but this relationship was nonlinear (P = 0.007) with striking differences between stage 4 (median area ratios, 12.3%) and stages 0-3 (2.1%, 2.8%, 4.3%, and 4.8%, respectively). Elastin accumulation was common in areas of thick bridging fibrosis and thickened venous walls but not in areas of perisinusoidal fibrosis. The highest tertile of the combined fiber area ratios was associated with the fibrosis-4 index and serum type IV collagen 7s domain (7s collagen) levels, whereas the upper two tertiles of the fiber amounts significantly associated with body mass index, aspartate aminotransferase, and 7s collagen in the multivariable analysis. Conclusion: Quantitative fibrosis assessment reveals a nonlinear relationship between fibrosis stage and fiber amount, with a marked difference between stage 4 and stage 3 and much smaller differences among stages 0-3, suggesting a heterogeneity in disease severity within NAFLD-related cirrhosis. (Hepatology Communications 2018;2:58-68).

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生体腎移植後に持続血糖測定器による血糖変動の評価が有用であった2型糖尿病の3例

坂巻, 裕介, 香野, 日高, 橋口, 明典, 萩生田, 純, 萩原, 正幸, 高橋, 遼平, 與那嶺, 智子, 森田, 伸也, 篠田, 和伸, 林, 晃一, 中川, 健

腎移植・血管外科 (腎移植・血管外科研究会) 28 ( 1 ) 45 - 51 2017.10

Joint Work, ISSN 0915-9118

今回われわれは、生体腎移植後1年以内に、持続血糖測定(Continuous glucose monitoring;CGM)を行った2型糖尿病の3例を経験したので報告する。1例目は60歳代の男性、混合型インスリンで治療中に、随時血糖の上昇を認めCGMを施行、昼食後の血糖上昇と血糖変動幅の増大が認められ、超速効型インスリンを追加した。2例目は50歳代の女性、強化インスリン療法中に、食後の低血糖症状を認めCGMを施行、超速効型インスリンの投与時間を食前から食後へと変更する方針となった。3例目は40歳代の男性、BOT(Basal Supported Oral Therapy)治療中に、HbA1cの上昇を認めCGMを施行、食後の血糖上昇に伴う血糖変動幅の増大に対して、超速効型インスリンを開始する方針となった。このように、腎移植後の血糖変動パターンをCGMで評価することで腎移植後糖尿病のより良い治療が行える可能性が示唆された。(著者抄録)

Polycythemia, capillary rarefaction, and focal glomerulosclerosis in two adolescents born extremely low birth weight and premature

Asada, N., Tsukahara, T., Furuhata, M., Matsuoka, D., Noda, S., Naganuma, K., Hashiguchi, A. and Awazu, M.

Pediatr Nephrol (Springer Verlag) 32 ( 7 ) 1275 - 1278 2017.07

Joint Work, ISSN 1432-198X

BACKGROUND: Low birthweight infants have a reduced number of nephrons and are at high risk of chronic kidney disease. Preterm birth and/or intrauterine growth restriction (IUGR) may also affect peritubular capillary development, as has been shown in other organs. CASE-DIAGNOSIS/TREATMENT: We report two patients with a history of preterm birth and extremely low birthweight who showed polycythemia and renal capillary rarefaction. Patient 1 and 2, born at 25 weeks of gestation with a birthweight of 728 and 466 g, showed mild proteinuria at age 8 and 6 years, respectively. In addition to increasing proteinuria, hemoglobin levels became elevated towards adolescence and their serum erythropoietin (EPO) was high despite polycythemia. Light microscopic examination of renal biopsy specimens showed glomerular hypertrophy, focal segmental glomerulosclerosis, and only mild tubulointerstitial fibrosis. A decrease in the immunohistochemical staining of CD31 and CD34 endothelial cells in renal biopsy specimens was consistent with peritubular capillary rarefaction. CONCLUSIONS: Since kidney function was almost normal and fibrosis was not severe, we consider that the capillary rarefaction and polycythemia associated with elevated EPO levels were largely attributable to preterm birth and/or IUGR.

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【腎生検・病理診断-臨床と病理の架け橋】 (第2章)臨床医が知っておくべき腎生検標本の作製と観察の実際光顕の標本の作製と観察光顕所見を観察するうえでの基本と注意点

橋口, 明典

腎と透析 82 ( 増刊 ) 77 - 84 2017.05

Joint Work, ISSN 0385-2156

母体低栄養は片側尿管結紮による腎障害を増悪するラットモデルを用いた検討

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

【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

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

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