Papers - Hashiguchi, Akinori

病理最前線 腎臓-腎硬化症の語りかけるもの

橋口, 明典

医と食 1 ( 3 ) 2 - 3 2009.08

Joint Work,  ISSN  1883-6658

CKDの発症からシェーグレン症候群と診断に至った一例

侯 金成, 徳山 博文, 脇野 修, 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)  51 ( 6 ) 672 - 672 2009.08

Joint Work,  ISSN  0385-2385

肝硬変および糖尿病の影響が疑われた結節性糸球体硬化症の一例

水口 斉, 脇野 修, 立松 覚, 徳山 博文, 小西 孝之助, 林 晃一, 伊藤 裕, 橋口 明典

日本腎臓学会誌 ((一社)日本腎臓学会)  51 ( 6 ) 664 - 664 2009.08

Joint Work,  ISSN  0385-2385

クローン病に腎および腸管アミロイドーシスを合併した一例

籠尾 壽哉, 徳山 博文, 脇野 修, 橋口 明典, 小西 孝之助, 林 松彦, 林 晃一, 伊藤 裕

日本腎臓学会誌 ((一社)日本腎臓学会)  51 ( 6 ) 650 - 650 2009.08

Joint Work,  ISSN  0385-2385

治療抵抗性を示し15年間低補体血症が持続した後自然軽快した1型MPGNの1症例

上原 朋子, 遠海 重裕, 五月女 友美子, 松山 健, 本田 雅敬, 粟津 緑, 橋口 明典

日本小児腎臓病学会雑誌 ((一社)日本小児腎臓病学会)  22 ( 1Suppl. ) 123 - 123 2009.06

Joint Work, Accepted,  ISSN  0915-2245

Synuclein-gamma Is Closely Involved in Perineural Invasion and Distant Metastasis in Mouse Models and Is a Novel Prognostic Factor in Pancreatic Cancer

Hibi, Taizo, Mori, Taisuke, Fukuma, Mariko, Yamazaki, Ken, Hashiguchi, Akinori, Yamada, Taketo, Tanabe, Minoru, Aiura, Koichi, Kawakami, Takao, Ogiwara, Atsushi, Kosuge, Tomoo, Kitajima, Masaki, Kitagawa, Yuko, Sakamoto, Michiie

CLINICAL CANCER RESEARCH (AMER ASSOC CANCER RESEARCH)  15 ( 8 ) 2864 - 2871 2009.04

Research paper (scientific journal), Joint Work,  ISSN  1078-0432

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Purpose: Perineural invasion is associated with the high incidence of local recurrence and a dismal prognosis in pancreatic cancer. We previously reported a novel perineural invasion model and distinguished high- and low-perineural invasion groups in pancreatic cancer cell lines. This study aimed to elucidate the molecular mechanism of perineural invasion.
Experimental Design: To identify key biological markers involved in perineural invasion, differentially expressed molecules were investigated by proteomics and transcriptomics. Synuclein-gamma emerged as the only up-regulated molecule in high-perineural invasion group by both analyses. The clinical significance and the biological property of synuclein-gamma were examined in 62 resected cases of pancreatic cancer and mouse models.
Results: Synuclein-gamma overexpression was observed in 38 (61%) cases and correlated with major invasive parameters, including perineural invasion and lymph node metastasis (P < 0.05). Multivariate analyses revealed synuclein-gamma overexpression as the only independent predictor of diminished overall survival [hazard ratio, 3.4 (95% confidence interval, 1.51-7.51)] and the strongest negative indicator of disease-free survival [2.8 (1.26-6.02)]. In mouse perineural invasion and orthotopic transplantation models, stable synuclein-gamma suppression by short hairpin RNA significantly reduced the incidence of perineural invasion (P = 0.009) and liver/lymph node metastasis (P = 0.019 and P = 0.020, respectively) compared with the control.
Conclusions: This is the first study to provide in vivo evidence that synuclein-gamma is closely involved in perineural invasion/distant metastasis and is a significant prognostic factor in pancreatic cancer. Synuclein-gamma may serve as a promising molecular target of early diagnosis and anticancer therapy.

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腹腔鏡下右副腎摘除術、腹腔鏡下左副腎部分切除術を一期的に施行した両側副腎褐色細胞腫の1例

武田 利和, 宮嶋 哲, 柴田 洋孝, 橋口 明典, 菊地 栄次, 中川 健, 伊藤 裕, 大家 基嗣

日本内分泌外科学会総会プログラム・抄録集 ((一社)日本内分泌外科学会)  21回   105 - 105 2009.04

Joint Work

DVDバーチャルスライド教材の開発 病理実習教育の効率化に向けて

橋口, 明典, 武市, 光司, 坂元, 亨宇

病理と臨床 27 ( 3 ) 303 - 305 2009.03

Joint Work,  ISSN  0287-3745

第2世代超音波造影剤(ソナゾイド)による前立腺癌の腫瘍血管描出能に関する検討

松本 一宏, 中川 健, 橋口 明典, 香野 日高, 菊地 栄次, 長田 浩彦, 宮嶋 哲, 大家 基嗣

日本泌尿器科学会雑誌 ((一社)日本泌尿器科学会)  100 ( 2 ) 332 - 332 2009.02

Joint Work,  ISSN  0021-5287

弓状動脈にフィブリノイド血管壊死を呈したMPO-ANCA関連RPGN症候群の1例

伊藤 新, 徳山 博文, 脇野 修, 金子 友香, 竹本 崇史, 小西 孝之助, 林 松彦, 橋口 明典, 林 晃一, 伊藤 裕

日本内科学会関東地方会 (日本内科学会-関東地方会)  556回   33 - 33 2008.09

Joint Work

【進化するバーチャルスライド 現状と展望】 バーチャルスライドの学生教育への応用

橋口, 明典, 武市, 光司, 坂元, 亨宇

Medical Technology 36 ( 8 ) 813 - 817 2008.08

Joint Work,  ISSN  0389-1887

Histopathological features and prognostic significance of the micropapillary pattern in lung adenocarcinoma.

Kazunori Kamiya, Yuichiro Hayashi, Junya Douguchi, Akinori Hashiguchi, Taketo Yamada, Yotaro Izumi, Masazumi Watanabe, Masafumi Kawamura, Hirohisa Horinouchi, Naoki Shimada, Koichi Kobayashi, Michiie Sakamoto

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 21 ( 8 ) 992 - 1001 2008.08

Joint Work

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The micropapillary pattern is characterized by small papillary tufts with no fibrovascular core lying in spaces and has been reported as an aggressive variant of carcinoma in several organs. We investigated the histopathobiological properties of the micropapillary pattern with immunohistochemistry, serial sections, and electron microscopy in lung adenocarcinoma. We further analyzed its clinicopathological character and prognosis. The subjects included 383 adenocarcinoma cases, of which 184 (48%) were micropapillary pattern-positive and 199 (52%) were micropapillary pattern-negative. On histology, micropapillary tufts seemed to float in the alveolar space or spaces encased by connective tissues, whereas serial sections revealed that most tufts had continuity with other tufts and even with the main tumor. Positive staining for the adhesion molecules E-cadherin and beta-catenin suggested the preservation of tight adhesion, and electron microscopy showed the existence of intercellular junctions. Negative staining for laminin and loss of basement membrane as determined by electron microscopy suggest a loss of cell-matrix contact. Positive staining for Ki-67 indicates that cells constituting micropapillary tufts retained their proliferation potency. There were no CD34-positive cells in micropapillary tufts, and the loss of the vascular core was confirmed. In micropapillary pattern-positive cases, lymphatic invasion was identified significantly more frequently than in micropapillary pattern-negative cases (P<0.001), even at stageIA (without lymph node metastasis, N=197) (P<0.001). The 5-year and 10-year overall survival rates of the micropapillary pattern-positive stageIA group were 77.6 and 67.6%, respectively, which were significantly less than those of the micropapillary pattern-negative stageIA group (98.1 and 98.1%) (P=0.001). In conclusion, cells constituting the micropapillary pattern are likely to have acquired anchorage-independent growth and a potential for high malignancy.

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Prediction of extraprostatic extension by prostate specific antigen velocity, endorectal MRI, and biopsy Gleason score in clinically localized prostate cancer.

Koshiro Nishimoto, Jun Nakashima, Akinori Hashiguchi, Eiji Kikuchi, Akira Miyajima, Ken Nakagawa, Takashi Ohigashi, Mototsugu Oya, Masaru Murai

International journal of urology : official journal of the Japanese Urological Association (John Wiley & Sons Australia, Ltd)  15 ( 6 ) 520 - 3 2008.06

Joint Work, Accepted,  ISSN  0919-8172

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OBJECTIVES: To investigate the clinical value of prostate specific antigen velocity (PSAV) in predicting the extraprostatic extension of clinically localized prostate cancer. METHODS: One hundred and three patients who underwent radical prostatectomy for clinically localized prostate cancer were included in the analysis. The correlation between preoperative parameters, including PSA-based parameters, clinical stage, and histological biopsy findings, and the pathological findings were analyzed. Logistic regression analysis was performed to identify a significant set of independent predictors for the local extent of the disease. RESULTS: Sixty-four (60.2%) patients had organ confined prostate cancer and 39 (39.8%) patients had extraprostatic cancer. The biopsy Gleason score, PSA, PSA density, PSA density of the transition zone, and PSAV were significantly higher in the patients with extraprostatic cancer than in those with organ confined cancer. Multivariate logistic regression analysis indicated that the biopsy Gleason score, endorectal magnetic resonance imaging findings, and PSAV were significant predictors of extraprostatic cancer (P < 0.01). Probability curves for extraprostatic cancer were generated using these three preoperative parameters. CONCLUSIONS: The combination of PSAV, endorectal magnetic resonance imaging findings, and biopsy Gleason score can provide additional information for selecting appropriate candidates for radical prostatectomy.

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A case of atypical POEMS syndrome without polyneuropathy

Morizane, Ryuji, Sasamura, Hiroyuki, Minakuchi, Hitoshi, Takae, Yujiro, Kikuchi, Haruhito, Yoshiya, Naomi, Hashiguchi, Akinori, Konishi, Konosuke, Okamoto, Shinichiro, Itoh, Hiroshi

EUROPEAN JOURNAL OF HAEMATOLOGY (BLACKWELL PUBLISHING)  80 ( 5 ) 452 - 455 2008.05

Research paper (scientific journal), Joint Work,  ISSN  0902-4441

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POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, Skin changes) syndrome is a rare hematological disease associated with overproduction of pro-inflammatory cytokines. Under the current nomenclature and diagnostic criteria for POEMS syndrome, the presence of characteristic polyneuropathy is required for diagnosis. We report a 43-year-old Japanese woman with organomegaly, endocrinopathy, M-protein, skin lesions, as well as typical renal lesions and sclerotic bone lesions. Of note, neurological examinations and peripheral nerve conduction tests were normal in this patient. In view of the overwhelming number of otherwise characteristic signs and symptoms, we made a provisional diagnosis of 'atypical POEMS syndrome without polyneuropathy'. If further similar cases are reported in the future, reconsideration of the nomenclature and/or diagnostic criteria for POEMS syndrome may be required.

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前立腺癌の検出におけるMR拡散強調像の臨床的意義 全摘標本との対比

谷本 伸弘, 中島 淳, 篠田 和伸, 橋口 明典, 栗林 幸夫

泌尿器外科 (医学図書出版(株))  21 ( 臨増 ) 379 - 379 2008.03

Joint Work,  ISSN  0914-6180

腹部腫瘤を主訴とする後腹膜原発粘液嚢胞腺癌

伊藤, 祐二郎, 大家, 基嗣, 石田, 勝, 安藤, 利行, 橋口, 明典, 村井, 勝

臨床泌尿器科 62 ( 1 ) 57 - 59 2008.01

Joint Work,  ISSN  0385-2393

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症例は71歳,女性。腹部腫瘤を主訴に来院した。CT・MRIの結果,右下腹部に内部に充実成分を含む12×14×18cmの嚢胞性腫瘤を認めた。後腹膜原発の粘液嚢胞腺腫が疑われたが,悪性腫瘍が否定できなかったため,正中開腹にて後腹膜腫瘍摘出術を施行した。摘出標本の病理組織学的所見は粘液嚢胞腺癌であった。(著者抄録)

Mutated D4-guanine diphosphate-dissociation inhibitor is found in human leukemic cells and promotes leukemic cell invasion

Nakata, Yuji, Kondoh, Kensuke, Fukushima, Sachiko, Hashiguchi, Akinori, Du, Wenlin, Hayashi, Mutsumi, Fujimoto, Jun-Ichiroh, Hata, Jun-Ichi, Yamada, Taketo

EXPERIMENTAL HEMATOLOGY (ELSEVIER SCIENCE INC)  36 ( 1 ) 37 - 50 2008.01

Research paper (scientific journal), Joint Work,  ISSN  0301-472X

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Objective. Rho GTPase may be involved in human cancer invasion via the augmentation of cell motility and adhesion. We report on two point mutations of the D4-guanine diphosphate (GDP)-dissociation inhibitor (GDI) gene, one of the Rho-GDIs, which were found in a human leukemic cell line, Reh, and the mutated D4-GDI functions as an accelerator of leukemic cell invasion.
Material and Methods. We investigated the altered activity of GDP dissociation by mutated (mt) D4-GDI and the functions of this mt and wild-type (wt) D4-GDI in invasion. The mice inoculated with wt or mt D4-GDI vector-transfected Raji cells were observed and examined pathologically. Adhesiveness and cell motility of wt or mt D4-GDI vector-transfected Raji cells were examined. Finally, it was examined whether Rho activation was changed by mutation of D4-GDI under the condition of Rho-GDI knockdown.
Results. Two point mutations of the D4-GDI gene were found in Reh cells. The region of mutations is conserved among members of the Rho-GDI family at the amino acid level. D4-GDI with two mutations (V68L and V69A) functioned in a dominant negative manner in the inhibition of GDP dissociation from Rho. Severe combined immune-deficient mice inoculated with Raji cells developed hemiparalysis. The Raji cells were present in bone marrow and peripheral blood, and hepatic invasion was observed in 20% of the mice. Mice inoculated with wt D4-GDI vector-transfected Raji cells (wt 134) showed later paralysis and none developed hepatic invasion. Mice inoculated with mt D4-GDI-transfected Raji cells (mt D4) showed a 5-day reduction in the time to paraplegia and death. In addition, hepatic invasion was evident in 80% of mice transplanted with mt D4 cells. There were no differences in growth rates and amounts of guanine triphosphate (GTP)-bound Rho, cdc42, or Rac among all clones, however, GTP-bound Rho in mt D4 clone with short hairpin RNA (shRNA) vector for Rho-GDI knockdown was increased compared with wt D4 clone with shRNA vector for Rho-GDI knockdown. The mt D4 cells showed an augmentation of adhesiveness and cell motility. On the other hand, wt D4 cells showed a decreased ability of cell motility.
Conclusion. These results suggest the mutated D4-GDI functions as a dominant negative molecule against the wt D4-GDI and accelerates invasion via regulation of cytoskeletal machinery. (c) 2008 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.

A case of primary retroperitoneal cystadenocarcinoma

Ito Yujiro, Oya Mototsugu, Ishida Masaru, Ando Toshiyuki, Hashiguchi Akinori, Murai Masaru

Japanese Journal of Clinical Urology 62 ( 1 ) 57 - 59 2008

Joint Work,  ISSN  0385-2393

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&lt;p&gt;A 71-year-old woman was admitted to our hospital complaining of right lower abdominal mass. Computed tomography, and magnetic resonance imaging showed a cystic tumor, 14 cm in diameter, located at the right lower abdomen with cyst wall calcification. Immunohistochemical staining was positive for CA19-9, but not for CEA and CA125. A transabdominal tumorectomy was performed. The removed tumor was 17.7 x 14.4 x 11.2 cm in size, weighing 1,870 g, and hisotopathological retroperitoneal cystadenocarcinoma.&lt;/p&gt;

腎細胞癌に合併したAL型原発性アミロイドーシスによってネフローゼ症候群を呈した1例

高野, 盛登, 須田, 徳子, 市原, 淳弘, 小西, 孝之助, 篠村, 裕之, 林, 晃一, 橋口, 明典, 宮嶋, 哲, 村井, 勝, 伊藤, 裕

日本腎臓学会誌 (Japanese Society of Nephrology)  49 ( 8 ) 1014 - 1019 2007.11

Joint Work,  ISSN  0385-2385

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症例は80歳、男性。2005年5月に食思不振を自覚し来院し、軽度蛋白尿と腹部CTで左腎細胞癌を認め、腹腔鏡下腎尿管摘出術を施行した。術後に蛋白尿がさらに増悪し下腿浮腫が出現したため、同年12月に精査目的で再入院した。蓄尿蛋白4.2g/日、血清TP 5.0g/dL,Alb 2.4g/dL,TC 214mg/dL,Cr 1.4mg/dL、クレアチニンクリアランス39mL/minよりネフローゼ症候群と診断されたが、精査により転移および他の悪性腫瘍の合併は否定された。摘出した左腎の非悪性腫瘍部位のHE染色による検討では、有意な異常所見を認めなかったが、念のためコンゴーレッドによる特殊染色をしたところ、小血管壁および糸球体にアミロイド沈着を認めた。アミロイド沈着は過マンガン酸カリウム処置後も残存しており、AL型原発性アミロイドーシスと診断した。その後、骨髄検査で多発性骨髄腫は否定され、尿蛋白電気泳動でわずかなベンスジョーンズ蛋白と上部消化管内視鏡で胃潰瘍病変部位のアミロイド沈着を認めた。腎細胞癌にAL型原発性アミロイドーシスを合併した症例報告はきわめて少なく、術後にネフローゼ症候群が顕在化したことを契機に摘出腎の詳細な検討を加えた結果、診断し得た貴重な症例と考えられた。(著者抄録)

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A case of nephrotic syndrome due to AL-type primary amyloidosis associated with renal cell carcinoma

Takano Morito, Suda Noriko, Ichihara Atsuhiro, Konishi Konosuke, Sasamura Hiroyuki, Hayashi Koichi, Hashiguchi Akinori, Miyajima Akira, Murai Masaru, Itoh Hiroshi

Japanese Journal of Nephrology 49 ( 8 ) 1014 - 1019 2007

Joint Work,  ISSN  0385-2385

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&lt;p&gt;An 80-year-old man was admitted because of appetite loss, mild proteinuria, and leg edema. A computed tomography examination revealed a tumor in his left kidney, and a left nephrectomy was performed. The tumor was histologically diagnosed as a clear cell type renal cell carcinoma, and hematoxylin eosin staining of the non-tumor region of the resected kidney showed an almost normal morphology. Three months later, he was readmitted because of the development of nephrotic syndrome with a urinary protein excretion of 4.2 g/day, a serum total protein concentration of 5.0 g/dL, a serum albumin concentration of 2.4 g/dL, a serum total cholesterol concentration of 214 mg/dL, and generalized edema. A full examination revealed no evidence of metastasis or recurrence of the renal cell carcinoma or any other malignant tumor. Congo red staining and immunohistochemical staining were performed using the non-tumor region of his resected kidney, and the presence of amyloid deposits in the microvascular walls and glomeruli that did not disappear when treated with potassium permanganate was disclosed. In this manner, the patient was diagnosed as having AL-type primary amyloidosis. Bence-Jones prot