研究者詳細 - 橋口　明典

Yuri Murakami, Tokiya Abe, Yoshiko Yamashita, Masahiro Yamaguchi, Masahiro Ishikawa, Akinori Hashiguchi, Kiyuna Tomoharu, Akira Saito, Michiie Sakamoto

Final Program and Proceedings - IS and T/SID Color Imaging Conference （Society for Imaging Science and Technology） 2014- （ January ） 184 - 188 2014年

共著, ISSN 2169-2629

We have been developing a prototype system for the automatic detection of hepatocellular carcinoma (HCC) from whole slide images (WSIs) of liver biopsy based on image analysis techniques. In this paper, we present two color-related topics of this system: color correction and the calculation of color-related features of cytoplasm. A WSI-basis color correction method was implemented for the prototype system. We tested the color correction using more than 300 WISs, and it was confirmed that the color correction works well and stably. In addition, it was found that the success rate of nuclei detection significantly increaseed due to color correction. As for color-related features, we propose a method to calculate the representative color of cytoplasm and the clearness of cytoplasm. It was found that there was slight difference between the distributions of the representative colors of HCC and non-cancer tissues. In addition, there was slight correlation between the clearness of cytoplasm and nuclei density, which implies a promising role of the clearness index in a nuclei-based HCC detection.

Renal thrombotic microangiopathy in a patient with septic disseminated intravascular coagulation

橋口明典

BMC NEPHROLOGY （BIOMED CENTRAL LTD） 14 3037 - 3045 2013年11月

研究論文（学術雑誌）, 共著, ISSN 1471-2369

Background: The mechanism for the development of thrombotic microangiopathy (TMA) during sepsis has only been partially elucidated. TMA is recognized as a disease caused by various factors, and may be involved in the emergence of organ damage in severe sepsis. Here we report a case of TMA that followed disseminated intravascular coagulation (DIC) due to severe infection in a patient with a reduced ADAMTS-13 activity level.
Case presentation: An 86-year-old Japanese woman was admitted to our hospital because of low back pain and fever. A careful evaluation led to a diagnosis of acute obstructive pyelonephritis due to a ureteral stone. Proteus mirabilis was isolated from both blood and urine cultures. The patient developed systemic inflammatory response syndrome and DIC, and was treated with antibiotics and daily continuous hemodiafiltration. Although infection and the coagulation abnormalities due to DIC were successfully controlled, renal failure persisted and her consciousness level deteriorated progressively in association with severe thrombocytopenia and microangiopathic hemolytic anemia. We therefore suspected the presence of TMA and started plasma exchange, which resulted in an impressive improvement in consciousness as well as the laboratory abnormalities. The ADAMTS-13 activity was 44% and the patient tested negative for the ADAMTS-13 inhibitor prior to the initiation of plasma exchange. A renal biopsy was performed to determine the etiology of acute renal injury, which revealed findings that were interpreted to be compatible with the sequelae of TMA. The follow-up studies performed after the successful treatment of TMA showed that her plasma ADAMTS-13 activity level remained persistently low. It is surmised that septic DIC occurring in the presence of preexisting reduced ADAMTS-13 activity have led to the development of secondary TMA in the present case.
Conclusion: The present case suggests that TMA can be superimposed on sepsis-induced DIC, and plasma exchange is expected to be beneficial in such situations. Clinicians should consider the possibility of secondary TMA that follows sepsis-induced DIC in certain indicative clinical settings.

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IgA腎症の寛解基準の提唱

松尾, 清一, 川村, 哲也, 鈴木, 祐介, 城, 謙輔, 富野, 康日己, 堀越, 哲, 西野, 友哉, 吉川, 徳茂, 服部, 元史, 木村, 健二郎, 安田, 隆, 白井, 小百合, 柴田, 孝則, 吉村, 光弘, 宇都宮, 保典, 遠藤, 正之, 坂本, なほ子, 松島, 雅人, 宮崎, 陽一, 安田, 宜成, 横尾, 隆, 香美, 祥二, 幡谷, 浩史, 鈴木, 仁, 松崎, 慶一, 内田, 俊也, 伊藤, 孝史, 清水, 章, 片渕, 律子, 久野, 敏, 橋口, 明典 and 厚生労働科学研究費補助金難治性疾患克服研究事業進行性腎障害に関する調査研究班報告IgA腎症分科会

日本腎臓学会誌（(一社)日本腎臓学会） 55 （ 7 ） 1249 - 1254 2013年10月

共著, ISSN 0385-2385

Clinical significance of quantitative measurement of elastin in liver biopsy

橋口明典

HEPATOLOGY 58 605A - 605A 2013年10月

研究論文（学術雑誌）, 共著, ISSN 0270-9139

HE染色肝病理組織標本における索状構造の配列の乱れ定量化法の提案

石川, 雅浩, 福井, 智也, 藤田, 悠介, 村上, 百合, 山口, 雅浩, 阿部, 時也, 橋口, 明典, 坂元, 亨宇 and 齋藤, 彰

MEDICAL IMAGING TECHNOLOGY 31 （ Suppl. ） 1 - 7 2013年08月

共著, ISSN 0288-450X

HE染色肝病理標本における肝細胞がんの診断では、細胞核や細胞配列など様々な形態学的特徴が用いられる。これらの画像解析に関する研究としては、従来、細胞核に着目した研究が多く報告されているが、がんの診断には、核の情報だけでは不十分である。本研究では、細胞配列に基づく特徴量を定量化することで、がんの検出や、分化度分類等に応用することを提案する。正常な肝組織では、肝細胞は索状に配列し、整然とした小葉構造を形成しているが、がんでは、これらの配列に乱れが生じる。これは小領域で考えた場合、正常では肝細胞索同士が並行に近い関係にあり、一定の方向性を持つのに対し、がんでは、細胞索の方向に規則性が失われると考えられる。そこで本研究では、細胞索同士で相対的な角度を算出し、その分布に基づく特徴量を求めた。提案法により、肝細胞の索状配列の特徴を定量化することで、肝細胞がんの識別に利用できる可能性が得られた。(著者抄録)

Bortezomibにより腎機能が回復した血管型ALアミロイドーシスの一例

中村俊文, 脇野修, 徳山博文, 中谷英章, 橋口明典, 小西孝之助, 林晃一, 伊藤裕

日本腎臓学会誌（(一社)日本腎臓学会） 55 （ 6 ） 1072 - 1072 2013年08月

共著, ISSN 0385-2385

骨髄非破壊的同種末梢血幹細胞移植11年経過後に発症した、著明な高血圧・ネフローゼ症候群の一例

松浦友一, 脇野修, 徳山博文, 篠塚圭祐, 小西孝之助, 橋口明典, 伊藤裕

日本腎臓学会誌（(一社)日本腎臓学会） 55 （ 6 ） 1038 - 1038 2013年08月

共著, ISSN 0385-2385

肺高血圧症を伴ったPOEMS症候群による腎機能障害の一例

篠塚圭祐, 脇野修, 徳山博文, 橋口明典, 小西孝之助, 林晃一, 伊藤裕

日本腎臓学会誌（(一社)日本腎臓学会） 55 （ 6 ） 1075 - 1075 2013年08月

共著, ISSN 0385-2385

Karyomegalic-like interstitial nephritisを呈したイフォスファミド腎症の1例

吉藤歩, 脇野修, 松浦友一, 徳山博文, 中村俊文, 橋口明典, 小西孝之助, 林晃一, 伊藤裕

日本腎臓学会誌（(一社)日本腎臓学会） 55 （ 6 ） 1068 - 1068 2013年08月

共著, ISSN 0385-2385

Suppression of autophagy by CUB domain-containing protein 1 signaling is essential for anchorage-independent survival of lung cancer cells

橋口明典

CANCER SCIENCE （WILEY-BLACKWELL） 104 （ 7 ） 865 - 870 2013年07月

研究論文（学術雑誌）, 共著, ISSN 1349-7006

CUB (C1r/C1s, urchin embryonic growth factor, BMP1) domain-containing protein 1 (CDCP1) has been implicated in promoting metastasis of cancer cells through several mechanisms, including the inhibition of anoikis, which is cell death triggered by the loss of extracellular matrix interactions. However, the mechanism inhibiting cell death regulated by CDCP1 remains elusive. Inhibition of CDCP1 expression using small interfering RNA (siRNA) induced the cell death of suspended cancer cells without cleaving caspase-3, a marker of apoptosis; cell death was not inhibited by a general caspase inhibitor, suggesting that the loss of CDCP1 induces caspase-independent cell death. In contrast, knockdown of CDCP1 as well as protein kinase C (PKC), a downstream effector of CDCP1, in a suspension culture of lung cancer cells resulted in marked induction of membranous microtubule-associated protein 1 light chain 3 (LC3)-II protein, a hallmark of autophagy, and caused the formation of an autophagosome structure visualized using green fluorescent protein-tagged LC3-II. Expression and phosphorylation of exogenous CDCP1 by Fyn kinase reduced the formation of autophagosomes and inhibited phosphorylation of CDCP1 by PP2, a Src kinase inhibitor or inhibited PKC by rottlerin, stimulating autophagosome formation. Moreover, death of suspended lung cancer cells induced by CDCP1 siRNA or by PKC siRNA was reduced by the autophagy inhibitor 3-methyladenine. CDCP1-PKC signaling plays a critical role in inhibiting autophagy, which is responsible for anoikis resistance of lung cancer cells.

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二期的根治手術を行った両側頸動脈小体腫瘍の1例

奥井, 文子, 冨田, 俊樹, 今西, 順久, 羽生, 昇, 佐藤, 陽一郎, 大塚, 邦憲, 小川, 郁, 橋口, 明典 and 杜, ぶん林

頭頸部外科（JAPAN SOCIETY FOR HEAD AND NECK SURGERY） 23 （ 1 ） 77 - 82 2013年06月

共著, ISSN 1349-581X

30歳男性の両側頸動脈小体腫瘍(左Shamblin I型、右Shamblin III型)に対し、二期的に根治手術を施行した。近医にてCT、MRIにより両側頸動脈小体腫瘍が疑われ、当院を紹介受診した。血管造影検査にて確定診断し、balloon Matas testは陰性であった。まずShamblin I型と思われた左側の手術を行い、頸動脈を温存し腫瘍を摘出した。5ヵ月後に行った右側の手術では、頸動脈分岐部を全周性に取り囲むShamblin III型であった。頸動脈分岐部を合併切除し、大伏在静脈により血行再建した。いずれも術前に栄養血管塞栓術を行った。血管造影検査と塞栓術を脳神経外科が、頸動脈再建術を血管外科が担当した。3科による集学的アプローチのもと、二期的に安全に両側腫瘍を摘出し得た症例を経験した。(著者抄録)

Quantification of collagen and elastic fibers using whole-slide images of liver biopsy specimens

橋口明典

PATHOLOGY INTERNATIONAL （WILEY-BLACKWELL） 63 （ 6 ） 305 - 310 2013年06月

研究論文（学術雑誌）, 共著, ISSN 1320-5463

Histological evaluation of fibrosis after a liver biopsy is crucial for evaluating the pathology of patients with chronic liver disease. Previous studies have reported quantitative analyses of fibrosis using images of collagen-stained sections. However, analysis of these studies requires manual selection of the region of interest. In addition, the quantification of elastic fibers is not considered. The present study was conducted in order to measure both the collagen and elastic fiber area ratios using Elastica van Gieson-stained whole-slide images (WSIs) of liver biopsy specimens. High-resolution WSIs provide precise color classification, enabling accurate detection of even fine collagen and elastic fibers. To minimize the influence of pre-existing fibrous tissue, median area ratios of the collagen and elastic fibers were independently calculated from the image tiles of the WSIs. These median area ratios were highly concordant with area ratios after the pre-existing fibrous tissues were manually trimmed from the WSI. Further, these median area ratios were correlated with liver stiffness as measured by transient elastography (collagen: r=0.73 [P<0.01], elastic: r=0.53 [P<0.01]). Our approach to quantifying liver fibrosis will serve as an effective tool to evaluate liver diseases in routine practice.

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Leukemia kidney infiltration can cause secondary polycythemia by activating hypoxia-inducible factor (HIF) pathway

橋口明典

EUROPEAN JOURNAL OF PEDIATRICS （SPRINGER） 172 （ 6 ） 829 - 832 2013年06月

研究論文（学術雑誌）, 共著, ISSN 0340-6199

Secondary polycythemia with increased production of erythropoietin (EPO) is known to occur in kidney diseases such as hydronephrosis and cystic disease, but the mechanism remains unclear. We report an 18-year-old female with isolated renal relapse of acute lymphoblastic leukemia accompanied by polycythemia. At the relapse, she presented with bilateral nephromegaly, mild renal dysfunction, and erythrocytosis with increased serum EPO levels up to 52.1 mIU/mL (9.1-32.8). Renal biopsy demonstrated diffuse lymphoblastic infiltration. The expression of hypoxia-inducible factor (HIF)-1 alpha, which is undetectable in normal kidney, was observed in the renal tubule epithelium compressed by lymphoblastic cells. These findings suggest that erythrocytosis was caused by renal ischemia due to leukemic infiltration. Polycythemia probably became apparent because of the lack of leukemic involvement of the bone marrow. With chemotherapy, the serum EPO level rapidly decreased to normal range accompanied by the normalization of kidney size and function. Renal leukemic infiltration may enhance EPO production, although not recognized in the majority of cases because of bone marrow involvement. C onclusion: Our case has clarified the mechanism of previously reported polycythemia associated with renal diseases as renal ischemia. Furthermore, we have added renal ischemia resulting from tumor infiltration to the list of causes of secondary polycythemia.

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CTガイド下腎生検にて診断し得た無症候性IgG4関連疾患の一例

寺西悠, 矢澤聰, 小坂威雄, 水野隆一, 菊地栄次, 長田浩彦, 浅沼宏, 宮嶋哲, 中川健, 中塚誠之, 橋口明典, 向井万起男, 大家基嗣

泌尿器外科（医学図書出版(株)） 26 （臨増） 761 - 761 2013年05月

共著, ISSN 0914-6180

定量的病理診断に向けた病理画像解析技術

山口, 雅浩, 長橋, 宏, 坂元, 亨宇, 橋口, 明典, 齋藤, 彰 and 小林, 直樹

電子情報通信学会論文誌D: 情報・システム（一般社団法人電子情報通信学会） 96 （ 4 ） 782 - 789 2013年04月

共著, ISSN 1880-4535

ディジタルスライド(バーチャルスライド、Whole Slide Imagingとも呼ばれる)技術の進歩に伴い、病理診断のディジタル化が期待されている。ディジタル技術の導入により、従来の病理医の視覚に頼る定性的/半定量的な診断から、画像計測・認識技術に基づいた定量的病理診断が可能になる。本論文では、筆者らが研究・開発に取り組んでいる病理画像認識、高精度画像解析、色補正などの技術を例示し、定量的病理診断の確立に向けた課題などについて議論を行う。(著者抄録)

CiNii Research

病理学　病理デジタル画像技術の進歩　デジタル病理学、パソロジー・インフォマティクス

橋口, 明典

医学のあゆみ 244 （ 6 ） 560 - 562 2013年02月

共著, ISSN 0039-2359

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