研究者データベース

大塚 紀幸(オオツカ ノリユキ)
医学研究院 病理系部門 病理学分野
助教

基本情報

所属

  • 医学研究院 病理系部門 病理学分野

職名

  • 助教

学位

  • MD(北海道大学)
  • PhD(北海道大学)

J-Global ID

研究キーワード

  • 卵巣   Fragile X症候群   三塩基リピート病   CGG repeat   POF   ナチュラルキラー細胞   NKG2D   活性化リガンド   免疫監視   皮膚免疫   がん   MHC   

研究分野

  • ライフサイエンス / 実験病理学

職歴

  • 2012年 北海道大学 医学(系)研究科(研究院) 助教

研究活動情報

論文

  • Takuji Ota, Toshiya Kamiyama, Takuya Kato, Takayuki Hanamoto, Kunihiro Hirose, Noriyuki Otsuka, Shinichi Matsuoka, Akinobu Taketomi
    Surgical case reports 6 1 251 - 251 2020年10月01日 
    BACKGROUND: Hepatic cavernous hemangioma (CH) is the most common hepatic benign tumor. Most cases are solitary, asymptomatic, and found incidentally. In symptomatic cases with rapidly growing tumors and coagulopathy, surgical treatment is considered. In rare cases, diffuse hepatic hemangiomatosis (DHH) is reported as a comorbidity. The etiology of DHH is unknown. CASE PRESENTATION: A 29-year-old female patient had a history of endometriosis treated with oral contraceptives. Hepatic CH was incidentally detected in the segment IVa of the liver according to the Couinaud classification. Follow-up computed tomography (CT) and ultrasound sonography showed the growth of the lesion and formation of multiple new lesions near the first. Enhanced CT and magnetic resonance imaging (MRI) revealed that the new lesions were different from CH. Although oral contraceptives were stopped, all lesions grew in size. Malignancy and possibility of rupture of these tumors were considered due to the clinical course, and we opted for surgical removal of the tumors. Left liver lobectomy and cholecystectomy were performed. Surgical findings were small red spot spreading and a mass in segment IV of the liver. Pathological examination revealed a circumscribed sponge-like tumor with diffuse irregular extension to the adjacent area. Both of the lesions consisted of blood-filled dilated vascular spaces lined by flat endothelium without atypia. The diagnosis was hepatic CH with DHH. The patient was discharged on postoperative day 12 uneventfully. CONCLUSION: We report the successful resection of CH with DHH. The case findings suggest a relationship between oral contraceptive use and enlargement of CH and DHH. Although DHH has been poorly understood, a few previously published cases reported DHH occurrence in patients using oral contraceptives. In such cases, the decision to perform surgical resection should be made after careful examination.
  • Takayuki Kiuchi, Utano Tomaru, Akihiro Ishizu, Makoto Imagawa, Sari Iwasaki, Akira Suzuki, Noriyuki Otsuka, Yoshihito Ohhara, Ichiro Kinoshita, Yoshihiro Matsuno, Hirotoshi Dosaka-Akita, Masanori Kasahara
    Journal of clinical pathology 2020年09月17日 
    AIM: The immunoproteasome is a specific proteasome isoform whose proteolytic activity enhances the generation of antigenic peptides to be presented by major histocompatibility complex class I molecules to CD8+ T cells. Physiologically, it is expressed abundantly in immune cells and is induced in somatic cells by cytokines, especially interferon-γ. Recently, variable expression of immunoproteasomes has been demonstrated in different types of cancers. However, the clinical significance of immunoproteasome expression in malignant tumours is poorly understood. In this study, we performed clinicopathological evaluation of immunoproteasome subunit β5i in non-small cell lung carcinomas (NSCLCs). METHODS: Tumour tissues were collected from 155 patients with NSCLCs, and immunohistochemical analysis for β5i was performed in relation to the prognosis of patients. RESULTS: High expression of β5i was found in about 20% of all NSCLCs and was found significantly more frequently (40%) in the adenocarcinoma subset. High expression of β5i was associated with a better 5-year relative survival rate in patients with pStage I to II adenocarcinoma and was also a significant and independent favourable prognostic factor in adenocarcinoma patients. In addition, when we performed in vitro analysis using NSCLC cell lines, combined treatment with the immunoproteasome-specific inhibitor ONX0914 and the proteasome inhibitor MG132 enhanced cell death in β5i-expressing NSCLC cell lines. CONCLUSION: The expression of immunoproteasome can be explored as both a prognostic factor and a potential therapeutic target in NSCLCs. Since immunoproteasomes have crucial role in the antigen presentation, further studies may help to provide essential knowledge for therapeutic strategies in anticancer immunotherapy.
  • Naoko Yamaguchi, Utano Tomaru, Takayuki Kiuchi, Akihiro Ishizu, Takahiro Deguchi, Noriyuki Otsuka, Satoshi Tanaka, Katsuji Marukawa, Yoshihiro Matsuno, Masanobu Kitagawa, Masanori Kasahara
    Journal of clinical pathology 2020年05月28日 
    AIM: Cathepsins are proteases that regulate a wide range of physiological processes, including protein turnover, cell signalling and antigen presentation. Recent studies have shown that cathepsins are highly upregulated in many types of tumours. Of the 15 cathepsins in humans, cathepsins V and S are abundantly expressed in the thymus, and we previously showed that the immunostaining of these cathepsins could serve as diagnostic markers for thymic epithelial tumours. However, little is known about the expression of other cathepsins in thymic epithelial tumours. To determine the diagnostic implications of cathepsins, we performed immunohistochemical analysis of cathepsin B (CTB), cathepsin D (CTD) and cathepsin K (CTK), all of which have been reported to correlate with the progression of squamous cell carcinoma. METHODS: The association between cathepsin expression and clinicopathological features was evaluated in 122 cases of thymoma and thymic carcinoma. RESULTS: CTB and CTD were frequently expressed in type A and type AB thymomas. In contrast, CTB and CTD were significantly less common in type B thymomas than in type A or AB thymomas. In type AB thymomas, the expression of CTB correlated with histological features, and was found predominantly in the type A component. Notably, CTK was expressed most commonly in thymic carcinomas, and patients who died of the disease showed increased expression of CTK. CONCLUSIONS: The expression of CTB and CTD correlated with the histological subtype of thymoma. In addition, the expression of CTK appears to be useful for the diagnosis of thymic carcinomas and as a prognostic marker.
  • Junichi Nakamura, Ichizo Tsujino, Gaku Yamamoto, Toshitaka Nakaya, Kei Takahashi, Hirokazu Kimura, Takahiro Sato, Taku Watanabe, Shimpei Nakagawa, Noriyuki Otsuka, Hiroshi Ohira, Satoshi Konno
    Respiratory medicine case reports 31 101215 - 101215 2020年 
    Pulmonary capillary hemangiomatosis (PCH) is a rare cause of pulmonary hypertension (PH) associated with poor prognosis. Clinically, it is characterized by severe hypoxemia, centrilobular ground-glass opacities on computed tomography, and pulmonary congestion triggered by pulmonary vasodilating therapy. In some cases, PCH has been reported to develop with other disorders including connective tissue disease; however, to date, no reports have described PCH in a patient with rheumatoid arthritis. We report a case of a 59-year-old male PCH patient with rheumatoid arthritis and associated pulmonary fibrosis. He was initially diagnosed with severe group 3 PH and received sildenafil, which generated a favorable hemodynamic response. However, 5 years later, his pulmonary hemodynamics deteriorated, and he died at the age of 67. An autopsy was performed, and thickening of alveolar septa and capillary proliferation, pathological features of PCH, were extensively observed in both lungs. We discuss when PCH developed, how sildenafil improved his hemodynamics, and how PCH could be clinically detected by noninvasive evaluations.
  • Jong Kun Park, Noriyuki Otsuka, Utano Tomaru, Hiroaki Suzuki, Manabu Azuma, Kazuhira Okamoto, Katsushige Yamashiro, Masanori Kasahara
    Human pathology 80 104 - 112 2018年10月 [査読有り][通常論文]
     
    PSF3 (Partner of SLD Five 3) is a member of the heterotetrameric complex termed GINS. Previous studies have shown that PSF3 is up-regulated in several cancers and is associated with tumor malignancy. However, the clinicopathological significance of PSF3 expression in endometrial lesions is still poorly understood. To investigate whether PSF3 could serve as a useful biomarker for endometrial carcinomas, we performed immunohistochemical analysis of PSF3 expression. In 155 cases of endometrial carcinomas (ECs), the mean tumor proportion score of PSF3 expression was 30.7% in G1 endometrioid carcinoma, 55.0% in G2 endometrioid carcinoma, 59.0% in G3 endometrioid carcinoma, and 58.9% in nonendometrioid carcinomas. In 25 cases of atypical hyperplasia, the mean tumor proportion score of PSF3 expression was significantly lower (10.4%). High expression of PSF3 was associated with more advanced pathologic T stage (P = .000), lymphatic invasion (P = .001), and poor clinical outcomes such as shorter relapse-free survival (P = .000) and overall survival (P = .001). When we compared the immunostaining of PSF3 and Ki-67, the proportions of PSF3-positive cells in tumor epithelial cells were comparable to those of Ki-67-positive cells. However, PSF3-positive cells were selectively found in tumor cells, whereas Ki-67-positive cells were also found in tumor stromal cells. These results demonstrated that PSF3 immunostaining was valuable as a histopathologic marker for differential diagnosis between atypical hyperplasia and ECs, for tumor histologic grading, and for determining a patient's prognosis. PSF3 may play a crucial role in tumor progression in EC.
  • Shizuka Kiuchi, Utano Tomaru, Akihiro Ishizu, Makoto Imagawa, Takayuki Kiuchi, Sari Iwasaki, Akira Suzuki, Noriyuki Otsuka, Takahiro Deguchi, Tomohiro Shimizu, Katsuji Marukawa, Yoshihiro Matsuno, Masanori Kasahara
    Human pathology 60 66 - 74 2017年02月 [査読有り][通常論文]
     
    Cathepsins are a group of proteolytic enzymes of the endosomal/lysosomal pathway involved in the thymic development of T cells restricted by major histocompatibility complex class II molecules. In the normal thymus, cathepsin V (CTV) and cathepsin S (CTS) are expressed in cortical and medullary epithelial cells, respectively. To investigate whether cathepsins could serve as a diagnostic marker, we performed immunohistochemical analysis for CTV and CTS in 77 cases of thymic epithelial tumors. Almost all cases (59/60) of thymoma expressed CTV, whereas 28 of 60 cases of thymoma expressed CTS. Notably, CTS was expressed in most cases of type A and type AB thymomas, but not in type B thymoma. The expression of cathepsins in type AB thymoma showed a clear correlation with histologic features; CTV was found predominantly in the type B component, and CTS was frequently expressed in the type A component. In thymic carcinoma, CTV was expressed in less than half cases (7/17), and the ratio of CTS-positive cases was equivalent to that of thymoma (8/17). Cases of CTV-negative thymic carcinoma tended to have a higher incidence of recurrence than did CTV-positive cases. Although further studies with a larger number of cases are required to confirm the utility of cathepsin immunostaining, CTV and CTS appear to serve as auxiliary diagnostic and/or prognostic markers in thymic epithelial tumors.
  • Tomaru U, Tsuji T, Kiuchi S, Ishizu A, Suzuki A, Otsuka N, Ito T, Ikeda H, Fukasawa Y, Kasahara M
    Histopathology 67 2 235 - 44 2015年08月 [査読有り][通常論文]
     
    AIMS: The majority of patients with Down syndrome (DS), trisomy 21, have morphologically abnormal thymuses and present with intrinsic immunological abnormalities affecting mainly the cellular immune response. The aim of this study was to examine whether the expression of functionally important molecules is altered in thymic stromal cells in patients with DS. METHODS AND RESULTS: We analysed thymic tissues from patients with trisomy 13 (n = 4), trisomy 18 (n = 14) and trisomy 21 (n = 13) for histological alterations, and for the expression of functionally important molecules such as β5t, a thymoproteasome subunit, and cathepsins L and S. In patients with trisomy 13 and trisomy 18, the thymus was morphologically normal or showed only mild depletion of cortical thymocytes. In contrast, the thymus showed variable histological changes in patients with trisomy 21; six of 13 cases showed severe depletion of thymocytes accompanied by the disappearance of thymic lobular architecture. In such thymuses, spindle-shaped keratin-positive cells were densely distributed, and expression of β5t, but not of cathepsin L, was markedly decreased. CONCLUSIONS: The present study suggests that abnormal thymic architecture and decreased expression of functionally important molecules in thymic stromal cells may be involved in immunological abnormalities in DS patients.
  • Sari Iwasaki, Akira Suzuki, Takashi Fujisawa, Taiju Sato, Shinya Shirai, Mitsunori Kamigaki, Noriyuki Otsuka, Utano Tomaru, Akihiro Ishizu
    CARDIOVASCULAR PATHOLOGY 24 6 408 - 410 2015年07月 [査読有り][通常論文]
     
    An 80-year-old Japanese man, who had fever and generalized fatigue not improved by antibiotics, was admitted to our hospital. Laboratory data indicative of renal dysfunction and antineutrophil cytoplasmic antibody (ANCA) in the serum led to the consideration of ANCA-associated vasculitis as a differential diagnosis. However, before the diagnostic confirmation, he was found dead on the bed. Autopsy revealed necrotizing crescentic glomerulonephritis in the kidneys. In addition, necrotizing granulomatous vasculitis with infiltration of multinucleated giant cells and neutrophils but not eosinophils was present in multiple organs. The direct cause of death was presumed as cardiac arrest by lethal arrhythmia because vasculitic lesions were distributed widely in the cardiac walls, acute congestion was observed in the systemic organs, and other causes of death were ruled out. This report presents the unusual manifestation of cardiac small-vessel involvement in ANCA-associated vasculitis related to sudden death. (C) 2015 Elsevier Inc. All rights reserved.
  • Hiromi Fujita, Yutaka Hatanaka, Yoichi Sutoh, Yuta Suzuki, Koji Oba, Kanako C Hatanaka, Tomoko Mitsuhashi, Noriyuki Otsuka, Kazunori Fugo, Masanori Kasahara, Yoshihiro Matsuno
    The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 63 3 217 - 27 2015年03月 [査読有り][通常論文]
     
    The MHC class I-chain-related proteins (MICs) and the UL16-binding proteins (ULBPs) are inducible stress response molecules that work as activators of a specific receptor, NKG2D, which is expressed on effector cells, such as NK cells and subsets of T cells. In this study, we sought to explore the biological significance of NKG2D ligands in human neoplasms by comprehensively examining the immunohistochemical expression profile of NKG2D ligands in a variety of human epithelial neoplasms. Following careful validation of the immunohistochemical specificity and availability of anti-human ULBP antibodies for formalin-fixed paraffin-embedded (FFPE) materials, the expression of NKG2D ligands was analyzed in FFPE tissue microarrays comprising 22 types of epithelial neoplastic tissue with their non-neoplastic counterpart from various organs. Hierarchical cluster analysis demonstrated a positive relationship among ULBP2/6, ULBP3, ULBP1, and ULBP5, whose expression patterns were similar across all of the neoplastic tissues examined. In contrast, MICA/B, as well as ULBP4, did not appear to be related to any other ligand. These expression profiles of NKG2D ligands in human neoplasms based on well-validated specific antibodies, followed by hierarchical cluster analysis, should help to clarify some functional aspects of these molecules in cancer biology, and also provide a path to the development of novel tumor-type-specific treatment strategies.
  • Rania Hassan Mohamed, Yoichi Sutoh, Yasushi Itoh, Noriyuki Otsuka, Yukiko Miyatake, Kazumasa Ogasawara, Masanori Kasahara
    PloS one 10 4 e0123258  2015年 [査読有り][通常論文]
     
    Dendritic epidermal T cells, which express an invariant Vγ5Vδ1 T-cell receptor and account for 95% of all resident T cells in the mouse epidermis, play a critical role in skin immune surveillance. These γδ T cells are generated by positive selection in the fetal thymus, after which they migrate to the skin. The development of dendritic epidermal T cells is critically dependent on the Skint1 gene expressed specifically in keratinocytes and thymic epithelial cells, suggesting an indispensable role for Skint1 in the selection machinery for specific intraepithelial lymphocytes. Phylogenetically, rodents have functional SKINT1 molecules, but humans and chimpanzees have a SKINT1-like (SKINT1L) gene with multiple inactivating mutations. In the present study, we analyzed SKINT1L sequences in representative primate species and found that all hominoid species have a common inactivating mutation, but that Old World monkeys such as olive baboons, green monkeys, cynomolgus macaques and rhesus macaques have apparently functional SKINT1L sequences, indicating that SKINT1L was inactivated in a common ancestor of hominoids. Interestingly, the epidermis of cynomolgus macaques contained a population of dendritic-shaped γδ T cells expressing a semi-invariant Vγ10/Vδ1 T-cell receptor. However, this population of macaque T cells differed from rodent dendritic epidermal T cells in that their Vγ10/Vδ1 T-cell receptors displayed junctional diversity and expression of Vγ10 was not epidermis-specific. Therefore, macaques do not appear to have rodent-type dendritic epidermal T cells despite having apparently functional SKINT1L. Comprehensive bioinformatics analysis indicates that SKINT1L emerged in an ancestor of placental mammals but was inactivated or lost multiple times in mammalian evolution and that Skint1 arose by gene duplication in a rodent lineage, suggesting that authentic dendritic epidermal T cells are presumably unique to rodents.
  • Shunji Ikeshita, Yukiko Miyatake, Noriyuki Otsuka, Masanori Kasahara
    Experimental and molecular pathology 97 1 171 - 5 2014年08月 [査読有り][通常論文]
     
    Infiltrating macrophages accumulate in fatty streak lesions and transform into foam cells, leading to the formation of atherosclerotic plaques. Inflammatory mechanisms underlying the plaque formation mediated by NKG2D-positive lymphocytes such as CD8+ T cells, natural killer cells and natural killer T cells have been extensively investigated. Yet, the involvement of the NKG2D system itself remains poorly understood. Recent work in mouse models has shown that blockade of an NKG2D receptor-ligand interaction reduces plaque formation and suppresses inflammation in aortae. In this study, we conducted immunohistochemical analysis of NKG2D ligand expression in autopsy-derived aortic specimens. Foam cells expressing NKG2D ligands MICA/B were found in advanced atherosclerotic lesions accompanied by a large necrotic core or hemorrhage. Human monocyte-derived macrophages treated in vitro with acetylated low-density lipoproteins enhanced expression of MICA/B and scavenger receptor A, thus accounting for NKG2D ligand expression in foam cells infiltrating atherosclerotic plaques. Our results suggest that, as in mice, the NKG2D system might be involved in the development of atherosclerosis in humans.
  • T. Imamoto, D. Nakazawa, H. Shida, A. Suzuki, N. Otsuka, U. Tomaru, A. Ishizu
    CLINICAL AND EXPERIMENTAL RHEUMATOLOGY 32 1 149 - 150 2014年01月 [査読有り][通常論文]
  • Seiji Tsunematsu, Mitsuteru Natsuizaka, Hiromi Fujita, Noriyuki Otsuka, Katsumi Terashita, Fumiyuki Sato, Tomoe Kobayashi, Masato Nakai, Yoko Tsukuda, Hiromasa Horimoto, Takuya Sho, Goki Suda, Mitsuru Nakanishi, Satoshi Hashino, Makoto Chuma, Naoya Sakamoto
    Internal medicine (Tokyo, Japan) 53 18 2079 - 82 2014年 [査読有り][通常論文]
     
    Hepatosplenic gamma-delta T-cell lymphoma (HSTCL) is a rare, aggressive subset of peripheral T-cell lymphoma. It has been reported that Epstein-Barr virus (EBV) infection can cause HSTCL; however, such cases are extremely rare, with only a few cases having been reported to date. We herein report an autopsy case of HSTCL associated with EBV infection. The presence of EBV infection was confirmed in serum EBV DNA and on in-situ hybridization, and cytotoxic molecules, such as granzyme B, perforin and T-cell intracytoplasmic antigen (TIA)-1, were all positive in lymphoma cells. These findings indicate that stimulation of persistent EBV infection may have caused HSTCL in this patient.
  • Pulmonary veno-occlusive disease(PVOD)の一剖検例
    山田 洋介, 大塚 紀幸, 大平 洋, 辻野 一三, 深谷 進司, 外丸 詩野, 石津 明洋
    脈管学 53 December 242 - 243 (一社)日本脈管学会 2013年12月 [査読有り][通常論文]
  • Gloria E Hoffman, Wei Wei Le, Ali Entezam, Noriyuki Otsuka, Zhi-Bin Tong, Lawrence Nelson, Jodi A Flaws, John H McDonald, Sanjeeda Jafar, Karen Usdin
    The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 60 6 439 - 56 2012年06月 [査読有り][通常論文]
     
    FMR1 premutation (PM) alleles have 55-200 CGG·CCG-repeats in their 5' UTR. PM carriers are at risk of fragile X-associated tremor and ataxia syndrome (FXTAS). Females are also at risk for FX primary ovarian insufficiency (FXPOI). PM pathology is generally attributed to deleterious properties of transcripts with long CGG-tracts. For FXPOI, hormone changes suggest a reduced residual follicle pool. Whether this is due to a smaller than normal original follicle pool or an increased rate of follicle depletion is unclear. A FX-PM mouse the authors generated with 130 CGG·CCG-repeats in the endogenous Fmr1 gene recapitulates features of FXTAS. Here the authors demonstrate that the gross development of the ovary and the establishment of the primordial follicle pool is normal in these mice. However, these animals show a faster loss of follicles of all follicle classes, suggesting that the problem is intrinsic to the ovary. In addition, many oocytes show aberrant nuclear accumulation of FMRP and elevated levels of ubiquitination. Furthermore, PM follicles are smaller and have fewer granulosa cells (GCs) than normal. Thus, these animals have ovarian abnormalities involving both the oocytes and GCs that may shed light on the molecular basis of FXPOI in humans.
  • Shigeru Yoshida, Rania Hassan Mohamed, Mizuho Kajikawa, Jun Koizumi, Minami Tanaka, Kazunori Fugo, Noriyuki Otsuka, Katsumi Maenaka, Hideo Yagita, Hitoshi Chiba, Masanori Kasahara
    Journal of immunology (Baltimore, Md. : 1950) 188 8 3972 - 9 2012年04月15日 [査読有り][通常論文]
     
    Dendritic epidermal T cells (DETCs) found in mouse skin are NKG2D-positive γδ T cells involved in immune surveillance and wound repair. It is assumed that the interaction of an NKG2D receptor on DETCs and an MHC class I-like NKG2D ligand on keratinocytes activates DETCs, which then secrete cytokines promoting wound repair. However, direct evidence that DETC activation through NKG2D signaling promotes wound repair is not available. In the present study, we generated mAbs for an NKG2D ligand H60c previously suggested to be expressed specifically on skin keratinocytes. Local administration of H60c-specific mAb inhibited activation of DETCs and significantly delayed wound repair. Likewise, administration of NKG2D-specific mAb impaired wound repair to a similar extent. The delay in wound closure resulting from the blockade of the NKG2D pathway was comparable to that observed in γδ T cell-deficient mice. These results indicate that H60c/NKG2D interactions play a critical role in wound repair. Reassessment of binding affinities showed that H60c monomers bind to NKG2D with affinity (K(d) = 26 ± 3.2 nM) comparable to those of other high-affinity NKG2D ligands. H60c is transcribed not only in skin but also in tissues such as tongue and female reproductive tract known to contain epithelium-resident γδ T cells expressing invariant TCRs, suggesting a more general role for H60c in the maintenance of epithelial integrity.
  • 肺腺癌に伴うトルソー症候群により肺高血圧症を合併した一剖検例
    今本 鉄平, 大塚 紀幸, 山田 洋介, 外丸 詩野, 高階 太一, 石津 明洋, 笠原 正典
    日本病理学会会誌 101 1 439 - 439 (一社)日本病理学会 2012年03月 [査読有り][通常論文]
  • Takahiro Sato, Ichizo Tsujino, Hiroshi Ohira, Noriko Oyama-Manabe, Yosuke Yamada, Noriyuki Otsuka, Masaharu Nishimura
    Circulation journal : official journal of the Japanese Circulation Society 76 1 238 - 9 2012年 [査読有り][通常論文]
  • Noriyuki Otsuka, Zhi-Bin Tong, Konstantina Vanevski, Wei Tu, Mickie H Cheng, Lawrence M Nelson
    Endocrinology 152 6 2465 - 73 2011年06月 [査読有り][通常論文]
     
    Primary ovarian insufficiency (POI) resulting from ovarian autoimmunity is a poorly understood clinical condition lacking in effective treatments. Understanding the targets of the autoimmune response and induction of ovarian-specific tolerance would allow development of focused therapies to preserve fertility in an at-risk population. MATER (maternal antigen that embryos require) is a known ovarian autoantigen targeted in autoimmune syndromes of POI. We attempt to induce ovarian-specific tolerance via transgenic expression of the MATER antigen on potentially tolerogenic antigen-presenting cells (APC), which typically present antigen via the major histocompatibility complex (MHC) class II molecule. We hypothesize that expression of MATER in a MHC class II-dependent manner on APC can mediate induction of ovarian tolerance. We utilized a well-characterized murine model of ovarian autoimmunity, whereby oophoritis develops after d 3 neonatal thymectomy (NTx). Wild-type and transgenic mice, carrying an MHC Class II-driven Mater gene (IE-Mater), were subjected to NTx and assessed for evidence of autoimmune oophoritis. After disease induction by NTx, female mice carrying the IE-Mater transgene had significant reductions in histological oophoritis (56%) and circulating ovarian autoantibodies (28%) compared with wild-type females (94% and 82%, respectively). Incidence of other autoimmunity was unaffected as assessed by antinuclear autoantibodies. Transgenic expression of MATER in APC can induce antigen-specific tolerance with a significant reduction in ovarian autoimmunity. Lack of complete disease protection suggests that other antigens may also play a role in autoimmune oophoritis. As a known autoantigen in the human APS1 (autoimmune polyglandular syndrome type 1), which is associated with POI, MATER may represent a relevant target for future diagnostic and therapeutic clinical interventions.
  • N. Shinohara, M. Takahashi, T. Kamishima, H. Ikushima, N. Otsuka, A. Ishizu, C. Shimizu, H. Kanayama, K. Nonomura
    BRITISH JOURNAL OF CANCER 104 2 241 - 247 2011年01月 [査読有り][通常論文]
     
    BACKGROUND: To elucidate the incidence and mechanisms of sunitinib-induced thyroid atrophy, we investigated serial volumetric and functional changes, and evaluated histological changes of the thyroid gland in metastatic renal cell carcinoma patients who received sunitinib. METHODS: Thyroid volume (by computed tomography volumetry) and thyroid function were measured at baseline, during the treatment, and at post-treatment periods. Histological evaluation of the thyroid gland was performed in four autopsied patients. RESULTS: The median reduction rate in thyroid volume at last evaluation during sunitinib treatment was 30% in all 17 patients. The incidence of hypothyroidism during sunitinib treatment was significantly higher in the high reduction rate group (n - 8; more than 50% reduction in volume) than in the low reduction rate group (n 9; less than 50% reduction in volume). Half of the patients in the high reduction rate group exhibited a transient thyroid-stimulating hormone suppression, suggesting thyrotoxicosis during sunitinib treatment. Histological evaluation demonstrated atrophy of thyroid follicles and degeneration of follicular epithelial cells without critical diminution of vascular volume in the thyroid gland. CONCLUSION: Thyroid atrophy is frequently observed following sunitinib treatment and may be brought about by sunitinib-induced thyrotoxicosis or the direct effects of sunitinib that lead to degeneration of thyroid follicular cells. British Journal of Cancer (2011) 104, 241-247. doi: 10.1038/sj.bjc.6606029 www.bjcancer.com Published online 14 December 2010 (C) 2011 Cancer Research UK
  • Mitsuko Furuya, Kiyotaka Nagahama, Akihiro Ishizu, Noriyuki Otsuka, Yoji Nagashima, Ichiro Aoki
    Frontiers in bioscience (Elite edition) 3 2 549 - 61 2011年01月01日 [査読有り][通常論文]
     
    Malignant solid tumors require blood supply for their uncontrollable progression. Angiogenic blood vessels generally sprout from preexisting vascular cells. In addition, various types of precursor cells also participate in tumor neovascularization. They include endothelial progenitor cells, hematopoietic stem cells and mesenchymal stem cells that are stimulated and attracted into tumor lesion, in which a wide variety of proinflammatory factors are involved. Among key molecules, vascular endothelial growth factor (VEGF) works as a mastermind regulator. Humanized monoclonal antibodies targeting VEGF-mediated signaling pathways are currently used as the most pervasive drugs in several types of progressive tumors. Adverse effects of these drugs include hypertension and proteinuria. Such symptoms are widely observed in preeclamptic patients whose blood contain high amount of natural VEGF antagonist. Vasoactive G protein-coupled receptors (GPCRs)-mediated signalings such as renin-angiotensin system and chemokine axes are also noticed that they may become effective therapeutic targets. In this review, we discuss general view of angiogenic microenvironment in solid tumors, and highlight several key signaling molecules and inhibitory effects of them on the whole system.
  • Jun Kasamatsu, Yoichi Sutoh, Kazunori Fugo, Noriyuki Otsuka, Kazuya Iwabuchi, Masanori Kasahara
    Proceedings of the National Academy of Sciences of the United States of America 107 32 14304 - 8 2010年08月10日 [査読有り][通常論文]
     
    Jawless vertebrates such as lamprey and hagfish lack T-cell and B-cell receptors; instead, they have unique antigen receptors known as variable lymphocyte receptors (VLRs). VLRs generate diversity by recombining highly diverse leucine-rich repeat modules and are expressed clonally on lymphocyte-like cells (LLCs). Thus far, two types of receptors, VLRA and VLRB, have been identified in lampreys and hagfish. Recent evidence indicates that VLRA and VLRB are expressed on distinct populations of LLCs that resemble T cells and B cells of jawed vertebrates, respectively. Here we identified a third VLR, designated VLRC, in the lamprey. None of the approximately 100 VLRC cDNA clones subjected to sequencing had an identical sequence, indicating that VLRC can generate sufficient diversity to function as antigen receptors. Notably, the C-terminal cap of VLRC exhibits only limited diversity and has important structural differences relative to VLRA and VLRB. Single-cell PCR analysis identified LLCs that rearranged VLRC but not VLRA or VLRB, suggesting the presence of a unique population of LLCs that express only VLRC.
  • Hiroaki Koiwa, Ichizo Tsujino, Hiroshi Ohira, Keiichiro Yoshinaga, Noriyuki Otsuka, Masaharu Nishimura
    Circulation 122 5 535 - 6 2010年08月03日 [査読有り][通常論文]
  • Mizuho Kondo, Takako Maruoka, Noriyuki Otsuka, Jun Kasamatsu, Kazunori Fugo, Naoto Hanzawa, Masanori Kasahara
    Immunogenetics 62 7 489 - 490 2010年07月 [査読有り][通常論文]
  • Mizuho Kondo, Takako Maruoka, Noriyuki Otsuka, Jun Kasamatsu, Kazunori Fugo, Naoto Hanzawa, Masanori Kasahara
    Immunogenetics 62 7 441 - 50 2010年07月 [査読有り][通常論文]
     
    NKG2D is a major activating receptor of natural killer cells. Its ligands are major histocompatibility complex (MHC) class I-like molecules whose expression is induced by cellular stresses such as infections and tumorigenesis. Humans have two families of NKG2D ligands (NKG2DL): MHC class I-related chains (MIC) encoded in the MHC and UL16-binding proteins (ULBP) encoded outside the MHC. By contrast, mice have only the latter family of ligands; instead, they have non-MHC-encoded MILL molecules that are closely related to MIC, but do not function as NKG2DL. To gain insights into the origin and evolution of MIC, ULBP, and MILL gene families, we conducted comparative genomic analysis of NKG2DL family genes in five mammalian species. In the opossum MHC, we identified a ULBP-like gene adjacent to a previously described MIC-like gene, suggesting that ULBP genes were originally encoded in the MHC. The opossum genome also contained a transcribed MILL-like gene in a region syntenic to the rodent regions encoding MILL molecules. These observations indicate that MIC-, ULBP-, and MILL-like genes emerged before the divergence of placental and marsupial mammals. Comparison of the human, cattle, rat, mouse, and opossum genomes indicates that after emigration from the MHC, ULBP genes underwent extensive duplications in each species. In mice, some of the ULBP genes appear to have been translocated telomerically on the same chromosome, forming a major cluster of existent NKG2DL genes.
  • Naomi Sasaki, Yayoi Ogawa, Chihiro Iinuma, Utano Tomaru, Kazuaki Katsumata, Noriyuki Otsuka, Masanori Kasahara, Takashi Yoshiki, Akihiro Ishizu
    AIDS research and human retroviruses 25 9 889 - 96 2009年09月 [査読有り][通常論文]
     
    It has long been discussed whether endogenous retroviruses (ERVs) are involved in the pathogenesis of autoimmune diseases. Among various human endogenous retroviruses (HERVs), we have focused on HERV-R. To investigate the biological roles of HERV-R, we earlier established transgenic rats carrying the full sequence of the viral genome. In these HERV-R rats, however, no disease occurred. Another trigger that induces autoimmunity may be essential for the recognition of HERV-R products by the immune system. Thus, in this study, we mated HERV-R rats with env-pX rats (transgenic rats carrying the env-pX gene of human T cell leukemia virus type I) that develop autoimmune diseases, and generated double transgenic (DTG) rats. In DTG rats, autoimmune diseases occurred similarly in env-pX rats. Interestingly, deposition of rat IgM but not IgG was observed on the glomerular endothelial cells. Such IgM deposition was never seen in the parental HERV-R or env-pX rats. We considered that in situ formation of immune complexes consisted of the HERV-R env glycoprotein and anti-HERV-R env IgM antibodies (Abs) in DTG rats, according to the following evidence: (1) No dense deposit, representing deposition of circulating immune complexes, was seen on glomerular endothelial cells. (2) IgM Abs reactive with HERV-R env glycoprotein were generated in the serum. (3) HERV-R env glycoprotein was expressed in the kidney, specifically on glomerular endothelial cells. (4) IgM deposition was partly colocalized with the HERV-R env glycoprotein on the glomeruli. These findings strongly suggest that the HERV-R env glycoprotein is recognized as an autoantigen in the host with autoimmune diseases.
  • Utano Tomaru, Akihiro Ishizu, Shigeo Murata, Yukiko Miyatake, Sayuri Suzuki, Satomi Takahashi, Taku Kazamaki, Jiro Ohara, Tomohisa Baba, Sari Iwasaki, Kazunori Fugo, Noriyuki Otsuka, Keiji Tanaka, Masanori Kasahara
    Blood 113 21 5186 - 91 2009年05月21日 [査読有り][通常論文]
     
    The ubiquitin-proteasome pathway, which degrades intracellular proteins, is involved in numerous cellular processes, including the supply of immunocompetent peptides to the antigen presenting machinery. Proteolysis by proteasomes is conducted by three beta subunits, beta1, beta2, and beta5, of the 20S proteasome. Recently, a novel beta subunit expressed exclusively in cortical thymic epithelial cells was discovered in mice. This subunit, designated beta5t, is a component of the thymoproteasome, a specialized type of proteasomes implicated in thymic positive selection. In this study, we show that, like its mouse counterpart, human beta5t is expressed exclusively in the thymic cortex. Human beta5t was expressed in approximately 80% of cortical thymic epithelial cells and some cortical dendritic cells. Human beta5t was incorporated into proteasomes with two other catalytically active beta subunits beta1i and beta2i, forming 20S proteasomes with subunit compositions characteristic of thymoproteasomes. The present study demonstrates, for the first time, the existence of thymoproteasomes in the human thymic cortex, indicating that thymoproteasome function is likely conserved between humans and mice.
  • N. Otsuka, Y. Miyatake, A. Ishizu, S. Tanaka, Y. Yamamoto, H. Ikeda, T. Yoshiki
    AIDS RESEARCH AND HUMAN RETROVIRUSES 22 11 1148 - 1151 2006年11月 [査読有り][通常論文]
     
    To investigate the biological roles of human endogenous retrovirus-R (HERV-R) in vivo, we established transgenic rats carrying the full sequence of the viral genome with control of its own long terminal repeat promoter. The Env protein was expressed on the surface of the epidermis of fetal HERV-R transgenic rats on day 10 of gestation. The epidermal Env expression disappeared by day 18 of gestation. After day 18 of gestation, the Env protein was detected in the prickle layer of the esophageal epithelium of transgenic rats. Interestingly, it was not detected in the basal layer of the epithelium, and the expression in the granular layer was weaker than in the prickle layer. These findings suggest that expression of HERV-R is linked not only to the development but also to the differentiation of squamous cells. Next, we examined alterations in the expression of the HERV-R env gene in cultured human squamous cells after exposure to all-trans retinoic acids ( ATRA). The env expression was increased by ATRA in a dose-dependent manner, while the expression of transglutaminase 1 (TGM1), a terminal marker for squamous differentiation, was decreased. TGM1 is expressed in the granular layer of the squamous epithelium, and ATRA suppresses the differentiation of cultured squamous cells. Thus, these in vitro data also suggest that HERV-R expression is regulated by a mechanism closely related to the differentiation of squamous cells. This study is the first to demonstrate the association of HERV-R expression and differentiation of squamous cells.
  • Takahiro Tsuchikawa, Satoshi Kondo, Satoshi Hirano, Eiichi Tanaka, Yoshiyasu Anbo, Toshiaki Morikawa, Shunichi Okushiba, Noriyuki Otsuka, Tomoo Itoh, Hiroyuki Katoh
    Surgery today 35 3 256 - 8 2005年 [査読有り][通常論文]
     
    Cholangiocarcinomas are rarely mucinproducing. We report a case of mucin-producing cholangiocarcinoma successfully treated by curative left hepatectomy, resulting in long-term survival, with no evidence of tumor recurrence 111 months after resection. Immunohistochemical studies revealed a pattern of MUC-1 negativity and MUC-2 positivity, suggesting low malignant potential.
  • Yukiyo Yamamoto, Akihiro Ishizu, Hitoshi Ikeda, Noriyuki Otsuka, Takashi Yoshiki
    Pathobiology : journal of immunopathology, molecular and cellular biology 71 6 295 - 301 2004年 [査読有り][通常論文]
     
    OBJECTIVE: In patients with autoimmune diseases, blood vessels may be critically involved at the site of inflammation. For these patients, glucocorticoids (GC) are often used as therapeutics. The aim of this study is to determine the effects of GC on vascular endothelial cells which are under inflammatory conditions. METHODS: We examined the molecular expressions in human umbilical vein endothelial cells (HUVEC) induced by dexamethasone (Dex) and tumor necrosis factor (TNF)-alpha. Live cell number of HUVEC under exposure to Dex and TNF-alpha was also assayed. RESULTS: The cDNA array analysis showed that a number of genes were upregulated, but only a few were downregulated by Dex and TNF-alpha, respectively. Among them, thrombomodulin (TM) gene showed the least fold change when HUVEC were stimulated by TNF-alpha. Since TM inhibits blood coagulation, we took notice of molecules associated with coagulation and fibrinolysis. The quantitative real-time RT-PCR revealed that the expression of plasminogen activator inhibitor-1 (PAI-1) gene increased when HUVEC were exposed to Dex and TNF-alpha, respectively, and the corresponding augmentation of its protein expression was confirmed by immunohistochemistry. The expression of PAI-1 gene additively increased when Dex and TNF-alpha were added to stimulate HUVEC. Under our experimental conditions, TNF-alpha induced proliferation of HUVEC. On the other hand, Dex did not change the number of live cells regardless of stimulation by TNF-alpha. CONCLUSION: TNF-alpha can induce proliferation of vascular endothelial cells with downregulation of the anticoagulation molecule, TM, and upregulation of the anti-fibrinolysis molecule, PAI-1. Dex further increased the expression of PAI-1 gene in the cells stimulated by TNF-alpha, and did not reduce the effect on cell proliferation induced by TNF-alpha. These findings suggest that the balance of blood coagulation versus fibrinolysis may incline to coagulation when Dex and TNF-alpha cooperate on vascular endothelial cells.
  • Satoshi Tanaka, Hitoshi Ikeda, Noriyuki Otsuka, Yukiyo Yamamoto, Toshiaki Sugaya, Takashi Yoshiki
    Transgenic research 12 3 319 - 28 2003年06月 [査読有り][通常論文]
     
    Human endogenous retrovirus-R (HERV-R) is one of a full length HERV with a long open reading frame in the env region. The env transcripts are expressed in various human tissues. To investigate the biological role of HERV-R in vivo, we established two lines of transgenic rats carrying a full sequence of HERV-R under control of its own long terminal repeat (LTR) promoter. One line with tandem integration of multiple copies of the transgene expressed HERV-R mRNA in various organs with different expression levels and relatively higher in Harderian and submandibular salivary glands. In another line, the transgene was integrated as a single copy in a haploid and the expression was detected only in Harderian and submandibular salivary glands. In the placenta, one of the tissues with high levels of the HERV-R expression in humans, the transcription was evident starting the 12th day after gestation. A rabbit antiserum against synthetic peptides corresponding with the HERV-R env gene sequence led to detection of an 85 kDa product as a glycoprotein in the Harderian glands. While no pathological significance was observed in either line, the transgenic rat may prove to be a suitable model for analyzing the role of HERV-R function in vivo.

その他活動・業績

  • 京極 典憲, 岩井 和浩, 吉見 泰典, 細井 勇人, 松井 あや, 佐藤 暢人, 狭間 一明, 渡邊 幹夫, 大塚 紀幸, 平野 聡 日本消化器外科学会雑誌 50 (1) 33 -42 2017年01月 [査読無し][通常論文]
     
    症例は64歳の男性で,心窩部痛を主訴に来院した.精査にて下部胆管に腫瘍を認め,生検にてrosette様配列を呈する腫瘍細胞を認めた.免疫染色検査にてchromogranin A,synaptophysinが陽性であり胆管原発の神経内分泌癌(neuroendocrine carcinoma;以下,NECと略記)を疑い亜全胃温存膵頭十二指腸切除術を施行した.腫瘍細胞のKi-67指数は40%であり胆管原発large cell NEC(以下,LCNECと略記),pT3aN0M0 stage IIA(胆道癌取扱い規約第6版)と診断した.術後はtegafur/gimeracil/oteracil(S-1)による補助化学療法を行い24ヵ月間無再発生存中である.胆管原発NECの本邦報告例は51例とまれであり,さらに本症例は極めてまれなLCNECであり貴重な症例と考えられるため報告する.(著者抄録)
  • Noriyuki Otsuka, Misa Tokunaga, Youka Aoki, Masanori Kasahara JOURNAL OF REPRODUCTIVE IMMUNOLOGY 118 110 -110 2016年11月 [査読無し][通常論文]
  • 吉田 繁, MOHAMED Rania Hassan, 梶川 瑞穂, 小泉 潤, 田中 みなみ, 冨居 一範, 大塚 紀幸, 前仲 勝美, 八木田 秀雄, 千葉 仁志, 笠原 正典 北海道醫學雜誌 = Acta medica Hokkaidonensia 87 (6) 2012年11月01日 [査読無し][通常論文]
  • NKG2Dリガンドの創傷治癒における役割の解析
    笠原 正典, Mohamed Rania, 小泉 潤, 富居 一範, 大塚 紀幸, 吉田 繁 MHC: Major Histocompatibility Complex 18 (2) 153 -153 2011年08月 [査読無し][通常論文]
  • 大畑 善寛, 中野 剛, 前田 由起子, 久保 公三, 大塚 紀幸, 岡本 賢三 日本呼吸器学会雑誌 = The journal of the Japanese Respiratory Society 49 (4) 277 -81 2011年04月 [査読無し][通常論文]
     
    A 50-year-old man with a history of asbestos inhalation developed symptoms related to a metastatic brain tumor was admitted. Chest X-ray images showed an opacity in the left lower lung field. We were unable to differentiate between lung cancer and malignant pleural tumor using either transbronchial lung biopsy or computed tomography (CT)-guided needle biopsy. After 3 months the patient died from rapid disease progression despite radiation therapy, drainage of large quantities of the pleural effusion and chemotherapy. A diagnosis of asbestos-related pleomorphic carcinoma of the lung was made after autopsy and immunohistochemical examination of the tumor.
  • 谷野美智枝, 中村紘子, 木村太一, 大塚紀幸, 深澤雄一郎, 西川祐司, 池田健, 西原広史, 田中伸哉, 田中伸哉 日本病理学会会誌 100 (1) 376 2011年03月26日 [査読無し][通常論文]
  • 体表組織におけるナチュラルキラー細胞活性化リガンドH60cの役割
    吉田 繁, 小泉 潤, 富居 一範, 近藤 瑞穂, 大塚 紀幸, 笠原 正典 日本病理学会会誌 100 (1) 366 -366 2011年03月 [査読無し][通常論文]
  • ヒトNKG2Dリガンドの組織発現に関する免疫組織化学検討
    藤田 裕美, 須藤 洋一, 畑中 豊, 富居 一範, 大塚 紀幸, 松野 吉宏, 笠原 正典 日本病理学会会誌 100 (1) 367 -367 2011年03月 [査読無し][通常論文]
  • Mizuho Kondo, Takako Maruoka, Noriyuki Otsuka, Jun Kasamatsu, Kazunori Fugo, Naoto Hanzawa, Masanori Kasahara IMMUNOGENETICS 62 (10) 709 -710 2010年10月 [査読無し][通常論文]
  • N. Shinohara, M. Takahashi, T. Kamishima, H. Ikushima, N. Otsuka, A. Ishizu, A. Sazawa, H. Kanayama, K. Nonomura JOURNAL OF CLINICAL ONCOLOGY 28 (15) 2010年05月 [査読無し][通常論文]
  • 粘膜免疫におけるナチュラルキラー細胞活性化リガンドH60cの役割
    吉田 繁, 富居 一範, 近藤 瑞穂, 大塚 紀幸, 笠原 正典 日本病理学会会誌 99 (1) 272 -272 2010年03月 [査読無し][通常論文]
  • 近交系マウスにおけるNKG2Dリガンド遺伝子のコピー数多型
    富居 一範, 皿田 雄二, 笠松 純, 近藤 瑞穂, 吉田 繁, 須藤 洋一, 大塚 紀幸, 笠原 正典 日本病理学会会誌 99 (1) 274 -274 2010年03月 [査読無し][通常論文]
  • NKT細胞とその他の自然リンパ球 基礎的解析 第3のvariable lymphocyte receptorの同定(Identification of a novel variable lymphocyte receptor)
    須藤 洋一, 大塚 紀幸, 富居 一範, 笠原 正典 日本免疫学会総会・学術集会記録 39 59 -59 2009年11月 [査読無し][通常論文]
  • MPO-ANCA陽性であったが糸球体腎炎や血管炎は確認されず、間質性肺炎に感染症を合併して死亡した症例
    石津 明洋, 岩崎 沙理, 外丸 詩野, 武田 広子, 大塚 紀幸, 富居 一範, 笠原 正典, 清水 健一, 南須原 康行, 西村 正治 北海道医学雑誌 84 (5) 403 -403 2009年09月 [査読無し][通常論文]
  • 弛張熱で発症した原発性胆汁性肝硬変、自己免疫性肝炎合併シェーグレン症候群の1例
    河野 通仁, 佐藤 力, 野本 博司, 谷口 聡, 田村 元男, 山根 康昭, 浄土 智, 藤咲 淳, 石津 明洋, 大塚 紀幸, 富居 一範 北海道医学雑誌 84 (5) 403 -404 2009年09月 [査読無し][通常論文]
  • 吉田繁, 富居一範, 梶川瑞穂, 近藤瑞穂, 大塚紀幸, 前仲勝実, 笠原正典 MHC 16 (2) 178 -178 2009年08月25日 [査読無し][通常論文]
  • 吉田繁, 富居一範, 梶川瑞穂, 笠松純, 皿田雄二, 大塚紀幸, 笠原正典 日本病理学会会誌 98 (1) 366 2009年03月20日 [査読無し][通常論文]
  • 新規分子Variable lymphocyte receptor(VLR)の抗体代替試薬としての可能性
    須藤 洋一, 大塚 紀幸, 富居 一範, 笠原 正典 日本病理学会会誌 98 (1) 346 -346 2009年03月 [査読無し][通常論文]
  • 分子標的薬sunitinib投与症例における甲状腺萎縮の病理学的解析
    中村 静香, 大塚 紀幸, 鈴木 昭, 富居 一範, 外丸 詩野, 笠原 正典, 石津 明洋 日本病理学会会誌 98 (1) 400 -400 2009年03月 [査読無し][通常論文]
  • 特殊なリンパ球 NK細胞や他のリンパ球 マウスNKG2DリガンドH60cの皮膚免疫における役割
    吉田 繁, 富居 一範, 笠松 純, 皿田 雄二, 大塚 紀幸, 笠原 正典 日本免疫学会総会・学術集会記録 38 72 -72 2008年11月 [査読無し][通常論文]
  • 肺限局型MPO-ANCA関連血管炎と考えられた一剖検例
    外丸 詩野, 武田 広子, 岩崎 沙理, 大塚 紀幸, 富居 一範, 笠原 正典, 清水 健一, 南須原 康行, 西村 正治, 石津 明洋 日本病理学会会誌 97 (2) 33 -33 2008年09月 [査読無し][通常論文]
  • 新規NKG2DリガンドH60b、H60cの機能解析(Functional analysis of novel members of NKG2D ligand, H60b and H60c)
    富居 一範, 吉田 繁, 大塚 紀幸, 外丸 詩野, 笠原 正典 日本癌学会総会記事 67回 443 -444 2008年09月 [査読無し][通常論文]
  • 妻鹿 成治, 川崎 亮輔, 浅野 賢道, 狭間 一明, 岩井 和浩, 大塚 紀幸, 石津 明洋 日本呼吸器外科学会雑誌 22 (3) 2008年04月18日 [査読無し][通常論文]
  • NKG2DリガンドH60b、H60cの機能解析
    吉田 繁, 富居 一範, 大塚 紀幸, 外丸 詩野, 笠原 正典 日本病理学会会誌 97 (1) 203 -203 2008年03月 [査読無し][通常論文]
  • 大塚 紀幸 北海道医学雑誌 78 (6) 549 -56 2003年11月 [査読無し][通常論文]
  • N Otsuka, H Ikeda, S Tanaka, A Ishizu, T Yoshiki AIDS RESEARCH AND HUMAN RETROVIRUSES 19 S67 -S67 2003年 [査読無し][通常論文]
  • 白間 信行, 若林 修, 福元 伸一, 横内 浩, 原田 敏之, 小島 哲弥, 大泉 聡史, 本村 文宏, 山崎 浩一, 小倉 滋明, 秋田 弘俊, 西村 正治, 大塚 紀幸, 村上 貴久, 清水 道生 気管支学 : 日本気管支研究会雑誌 23 (5) 2001年07月25日 [査読無し][通常論文]
  • 上野 敦盛, 小関 至, 佐々木 茂, 山口 純央, 岩田 徳和, 金戸 宏行, 伊東 文生, 遠藤 高夫, 一宮 慎吾, 佐藤 昌明, 大塚 紀幸, 清水 道生, 松下 通明, 藤堂 省, 今井 浩三 日本消化器病學會雜誌 = The Japanese journal of gastro-enterology 98 (4) 436 -441 2001年04月 [査読無し][通常論文]
  • N Otsuka, H Ikeda, S Tanaka, A Ishizu, T Yoshiki AIDS RESEARCH AND HUMAN RETROVIRUSES 17 S17 -S17 2001年 [査読無し][通常論文]

受賞

  • 第31回日本生殖免疫学会総会・学術集会 学会賞(JRI賞)
     
    受賞者: 大塚 紀幸

教育活動情報

主要な担当授業

  • 臨床病理学
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 医学部
  • 基本医学研究
    開講年度 : 2020年
    課程区分 : 修士課程
    開講学部 : 医学院
    キーワード : 病理学の基礎 Basic Pathology
  • 基盤医学研究Ⅱ
    開講年度 : 2020年
    課程区分 : 博士後期課程
    開講学部 : 医学研究科
  • 基本医学総論
    開講年度 : 2020年
    課程区分 : 修士課程
    開講学部 : 医学院
    キーワード : 細胞と組織の基本的病的変化,疾患の種類と分類,疾患の病因と病態 Basic pathological changes in cells and tissues, types and classification of diseases, and causes and pathophysiology of diseases
  • 基盤医学研究Ⅰ
    開講年度 : 2020年
    課程区分 : 博士後期課程
    開講学部 : 医学研究科
  • 医学総論
    開講年度 : 2020年
    課程区分 : 博士後期課程
    開講学部 : 医学院
    キーワード : 疾患の分子機構、免疫、診断病理
  • 医学総論
    開講年度 : 2020年
    課程区分 : 博士後期課程
    開講学部 : 医学研究科
  • 基盤医学研究
    開講年度 : 2020年
    課程区分 : 博士後期課程
    開講学部 : 医学院
    キーワード : 実験病理学、人体病理学
  • 保健組織病理学
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 医学部
    キーワード : 循環器、呼吸器、消化器、造血器、内分泌器、泌尿・生殖器、運動器、皮膚・感覚器、神経系
  • 器官病理学
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 医学部
    キーワード : 循環器、呼吸器、消化器、造血器、内分泌器、泌尿・生殖器、運動器、皮膚・感覚器、神経系
  • 病理学
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 医学部
    キーワード : 細胞と組織の基本的病的変化,疾患の種類と分類,疾患の病因と病態
  • 臨床病理学
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 医学部
    キーワード : 臨床診断、病理診断、診断の根拠と鑑別診断、治療の評価
  • 病理学演習
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 医学部
    キーワード : 肉眼的病理診断、組織学的病理診断、最終診断、個体の総合的病態、ポスター/スライド発表
  • 病理学実習
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 医学部
    キーワード : 組織病理、光学顕微鏡、バーチャルスライド、免疫染色、スケッチ
  • 一般教育演習(フレッシュマンセミナー)
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 全学教育
    キーワード : 神経科学、計算論的神経科学、人獣共通感染症、ウイルスの病原性解明、病理、免疫、癌、細胞接着、呼吸器


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