研究者総覧

原口 竜摩 (ハラグチ リュウマ)

  • 大学院医学系研究科 医学専攻 准教授
Last Updated :2020/08/06

研究者情報

学位

  • 医学(熊本大学)

論文上での記載著者名

  • Ryuma Haraguchi

ホームページURL

科研費研究者番号

  • 00423690

ORCID ID

J-Global ID

研究キーワード

  • 発現制御   メチル化   エピジェネティクス   泌尿生殖系臓器   形態形成   発生生物学   

研究分野

  • ライフサイエンス / 解剖学 / 生殖臓器・骨組織
  • ライフサイエンス / 人体病理学
  • ライフサイエンス / 実験動物学 / マウス
  • ライフサイエンス / 実験病理学

経歴

  • 2018年04月 - 現在  愛媛大学大学院医学研究科・分子病理学講座准教授
  • 2012年11月 - 2018年03月  愛媛大学大学院医学研究科・分子病理学講座特任講師
  • 2011年07月 - 2012年10月  愛媛大学大学院医学研究科・分子病理学講座助教
  • 2008年12月 - 2011年06月  愛媛大学医学部附属病院・病理診断科助教
  • 2008年10月 - 2008年11月  愛媛大学大学院医学研究科・統合医科学分野助教
  • 2003年04月 - 2008年09月  熊本大学生命資源開発研究センター 技術開発分野GCOEプログラム細胞系譜研究ユニットリサーチアソシエイト

学歴

  • 1999年04月 - 2003年03月   熊本大学大学院 医学研究科博士課程   Kumamoto University
  • 1997年04月 - 1999年03月   久留米大学大学院 比較文化研究科修士課程   Graduate School of Comparative Studies of International Cultures and Societies
  • 1993年04月 - 1997年03月   鹿児島大学 工学部応用化学工学科   Faculty of Engineering   Department of Applied Chemistry and Chemical Engineering
  • 1990年04月 - 1993年03月   学校法人川島学園 れいめい高等学校

所属学協会

  • 日本解剖学会   日本臨床分子形態学会   アメリカ骨代謝学会   日本骨代謝学会   日本組織細胞化学会   日本病理学会   愛媛病理研究会   

研究活動情報

論文

  • New Insights into the Pathogenesis of Diabetic Nephropathy: Proximal Renal Tubules Are Primary Target of Oxidative Stress in Diabetic Kidney
    #Ryuma Haraguchi, Yukihiro Kohara, Kanako Matsubayashi, Riko Kitazawa, Sohei Kitazawa, #corresponding author
    Acta Histochem. Cytochem. 53 2 2020年04月 [有り][無し]
     研究論文(学術雑誌)
  • Yukihiro Kohara, Ryuma Haraguchi, Riko Kitazawa, Yuuki Imai, Sohei Kitazawa
    International journal of molecular sciences 21 8 2020年04月 [有り][有り]
     研究論文(学術雑誌) 
    The functional role of the Hedgehog (Hh)-signaling pathway has been widely investigated in bone physiology/development. Previous studies have, however, focused primarily on Hh functions in bone formation, while its roles in bone resorption have not been fully elucidated. Here, we found that cyclopamine (smoothened (Smo) inhibitor), GANT-58 (GLI1 inhibitor), or GANT-61 (GLI1/2 inhibitor) significantly inhibited RANKL-induced osteoclast differentiation of bone marrow-derived macrophages. Although the inhibitory effects were exerted by cyclopamine or GANT-61 treatment during 0-48 h (early stage of osteoclast differentiation) or 48-96 h (late stage of osteoclast differentiation) after RANKL stimulation, GANT-58 suppressed osteoclast formation only during the early stage. These results suggest that the Smo-GLI1/2 axis mediates the whole process of osteoclastogenesis and that GLI1 activation is requisite only during early cellular events of osteoclastogenesis. Additionally, macrophage/osteoclast-specific deletion of Smo in mice was found to attenuate the aging phenotype characterized by trabecular low bone mass, suggesting that blockage of the Hh-signaling pathway in the osteoclast lineage plays a protective role against age-related bone loss. Our findings reveal a specific role of the Hh-signaling pathway in bone resorption and highlight that its inhibitors show potential as therapeutic agents that block osteoclast formation in the treatment of senile osteoporosis.
  • Yukihiro Kohara, Ryuma Haraguchi, Riko Kitazawa, Sohei Kitazawa
    Biochemical and biophysical research communications 523 4 961 - 965 2020年03月 [有り][無し]
     
    Low density lipoprotein receptor-related protein 1 (LRP1), a multifunctional cell surface protein, is expressed in bone marrow-derived macrophages. While LRP1 is thought to be a suppressor of osteoclast differentiation at late stages, its function at early stages remains unclear. Here we demonstrate that Lrp1 stable knockdown by lentiviral short hairpin RNA in macrophage cell line RAW264 cells inhibited RANKL-induced osteoclast formation and osteoclastic master transcription factor Nfatc1 mRNA expression as assessed by quantitative RT-PCR. Furthermore, knockdown of the Lrp1 gene suppressed not only differentiation, but also proliferation, and inhibitory effects on osteoblastic ALP activity by osteoclast-derived humoral factors. Thus, we propose that LRP1 in macrophages is required for both differentiation into osteoclasts and osteoclast-osteoblast interactions.
  • Taiju Hyuga, Mellissa Alcantara, Daiki Kajioka, Ryuma Haraguchi, Kentaro Suzuki, Shinichi Miyagawa, Yoshiyuki Kojima, Yutaro Hayashi, Gen Yamada
    International Journal of Molecular Sciences 21 1 58  MDPI} {AG 2019年12月 [有り][無し]
     
    Hedgehog (Hh) signaling is an essential growth factor signaling pathway especially in the regulation of epithelial-mesenchymal interactions (EMI) during the development of the urogenital organs such as the bladder and the external genitalia (EXG). The Hh ligands are often expressed in the epithelia, affecting the surrounding mesenchyme, and thus constituting a form of paracrine signaling. The development of the urogenital organ, therefore, provides an intriguing opportunity to study EMI and its relationship with other pathways, such as hormonal signaling. Cellular interactions of prostate cancer (PCa) with its neighboring tissue is also noteworthy. The local microenvironment, including the bone metastatic site, can release cellular signals which can affect the malignant tumors, and vice versa. Thus, it is necessary to compare possible similarities and divergences in Hh signaling functions and its interaction with other local growth factors, such as BMP (bone morphogenetic protein) between organogenesis and tumorigenesis. Additionally, this review will discuss two pertinent research aspects of Hh signaling: (1) the potential signaling crosstalk between Hh and androgen signaling; and (2) the effect of signaling between the epithelia and the mesenchyme on the status of the basement membrane with extracellular matrix structures located on the epithelial-mesenchymal interface.
  • #Ryuma Haraguchi, Riko Kitazawa, Yukihiro Kohara, Aoi Ikedo, Yuuki Imai, Sohei Kitazawa, #corresponding author
    International journal of molecular sciences 20 23 2019年11月 [有り][有り]
     
    The longitudinal growth of long bone, regulated by an epiphyseal cartilaginous component known as the "growth plate", is generated by epiphyseal chondrocytes. The growth plate provides a continuous supply of chondrocytes for endochondral ossification, a sequential bone replacement of cartilaginous tissue, and any failure in this process causes a wide range of skeletal disorders. Therefore, the cellular and molecular characteristics of the growth plate are of interest to many researchers. Hedgehog (Hh), well known as a mitogen and morphogen during development, is one of the best known regulatory signals in the developmental regulation of the growth plate. Numerous animal studies have revealed that signaling through the Hh pathway plays multiple roles in regulating the proliferation, differentiation, and maintenance of growth plate chondrocytes throughout the skeletal growth period. Furthermore, over the past few years, a growing body of evidence has emerged demonstrating that a limited number of growth plate chondrocytes transdifferentiate directly into the full osteogenic and multiple mesenchymal lineages during postnatal bone development and reside in the bone marrow until late adulthood. Current studies with the genetic fate mapping approach have shown that the commitment of growth plate chondrocytes into the skeletal lineage occurs under the influence of epiphyseal chondrocyte-derived Hh signals during endochondral bone formation. Here, we discuss the valuable observations on the role of the Hh signaling pathway in the growth plate based on mouse genetic studies, with some emphasis on recent advances.
  • Kitazawa S, Haraguchi R, Kohara Y, Kitazawa R
    Acta histochemica et cytochemica 52 4 77 - 83 2019年08月 [有り][無し]
     
    The interleukin (IL)-4, 1,25(OH)2D3 and retinoic acid, increase surface expression of functional integrin αvβ3 on murine osteoclast precursors. All three agonists stimulate transcription of the β3 gene, leading to increased steady-state levels of mRNA this protein. By contrast, mRNA levels of αv remain unchanged. In each instance, the increase in the surface expression of the integrin results in increased migration of the cells onto an αvβ3 substrate. Because β3 subunit, except platelet where β3 subunit conform a dimer with αIIb, associates solely with αv subunit monogamously, while promiscuous αv subunit combines with various subunit, our present data support the idea that the β3 subunit governs the surface-expressed functional integrin complex.
  • Riko Kitazawa, Satomi Kinto-Shibahara, Ryuma Haraguchi, Yukihiro Kohara, Sohei Kitazawa
    Biochemical and biophysical research communications 515 2 268 - 274 2019年07月 [有り][無し]
     
    Receptor activator of NF-κB (RANK) expressed on osteoclasts and their precursors is a receptor for RANK ligand (RANKL). Signals transduced by RANKL-RANK interaction induce genes essential for the differentiation and function of osteoclasts. We have cloned a basic promoter region of the mouse RANK gene and have analyzed the transcription machinery by transcription factors such as PU.1 (-480), and MITF (-100). Here, we examined the regulatory mechanisms of RANK gene transcription through AP-1 binding site, agagctca (-240). RANK mRNA expression in pre-osteoclastic RAW264.7 cells was induced by Phorbol12-myristate13-acetate (PMA) and suppressed by protein kinase C (PKC) inhibitor calphostin C. In RAW264.7 cells, Fos knockdown by siRNA blocked the inducible effect of PMA on RANK expression. By EMSA, an oligonucleotide (-246/-238) showed DNA protein binding, the specificity of which was confirmed by block-shift assay with an anti-Fos antibody and by the addition of the excess of a cold consensus probe. Co-transfection with a Fos expression vector showed that Fos increased RANK promoter activity 6-fold in RAW264.7 cells, and the addition of PU.1 and MITF superinduced the activity more than twenty-fold by the addition of PU.1 and MITF. Mutagenesis of the putative AP-1 site (-240) blocked the inducible effect of Fos on promoter activity. Taken together, these results indicate that during the differentiation of bone marrow mono-nucleated cells into osteoclast precursors, RANK transcription is positively regulated by Fos/AP-1 through the binding element of its gene promoter, supporting the concept that Fos activation by continuous CSF-1 stimulation on macrophages triggers initial expression of RANK and, later, a positive feedback loop by RANKL-RANK interaction.
  • 骨巨細胞腫の病態と治療修飾
    北澤荘平, 木谷彰岐, 原口竜摩, 北澤理子
    愛媛医学 38 1 1 - 6 2019年 [無し][無し]
     研究論文(学術雑誌)
  • Sohei Kitazawa, Ryuma Haraguchi, Riko Kitazawa
    Histochemistry and cell biology 150 1 3 - 12 2018年07月 [有り][無し]
     
    Cytosine methylation plays a major role in the regulation of sequential and tissue-specific expression of genes. De novo aberrant DNA methylation and demethylation are also crucial processes in tumorigenesis and tumor progression. The mechanisms of how and when such aberrant methylation and demethylation occur in tumor cells are still obscure, however. To evaluate subtle epigenetic alteration among minor subclonal populations, morphology-oriented epigenetic analysis is requisite, especially where heterogeneity and flexibility are as notable as in the process of cancer progression and cellular differentiation at critical stages. Therefore, establishment of reliable morphology-oriented epigenetic studies has become increasingly important in not only the experimental but also the diagnostic field. By selecting a subset of cells based on characteristic morphological features disclosed by microdissection or in situ hybridization, we discovered how methylation at certain CpG sites outside of CpG islands would play a crucial epigenetic role in the versatility and flexibility of gene expression during cancer progression. In this review, we first introduce technical aspects of two morphology-oriented epigenetic studies: (1) histoendonuclease-linked detection of methylated sites of DNA (HELMET), and (2) padlock probe and rolling circle amplification (RCA) for in situ identification of methylated cytosine in a sequence-dependent manner. We then present our observation of a novel MeCP2-mediated gene-silencing mechanism through the addition of methylation to a single-CpG-locus upstream of the TATA-box of the receptor activator of NF-κB ligand (RANKL) and of secreted frizzled-related protein 4 (SFRP4) gene promoters.
  • Shoko Matsushita, Kentaro Suzuki, Aki Murashima, Daiki Kajioka, Alvin Resultay Acebedo, Shinichi Miyagawa, Ryuma Haraguchi, Yukiko Ogino, Gen Yamada
    Nature reviews. Urology 15 6 358 - 368 2018年06月 [有り][無し]
     
    The biology of masculinization is fundamentally important for understanding the embryonic developmental processes that are involved in the development of the male reproductive tract, external genitalia, and also the tumorigenesis of prostate cancer. The molecular mechanisms of masculinization are of interest to many researchers and clinicians involved in varied fields, including molecular developmental biology, cancer research, endocrinology, and urology. Androgen signalling is mediated by the nuclear androgen receptor, which has fundamental roles in masculinization during development. Various modes of androgen signalling, including 5α-dihydrotestosterone-induced regulation of mesenchymal cell proliferation, have been observed in masculinization. Such regulation is essential for regulating urogenital tissue development, including external genitalia development. Androgen-induced genes, such as MAFB, which belongs to the activator protein 1 (AP-1) superfamily of genes, have essential roles in male urethral formation, and disruption of its signalling can interfere with urethral formation, which often results in hypospadias. Another AP-1 superfamily gene, ATF3, could be responsible for some instances of hypospadias in humans. These androgen-dependent signals and downstream events are crucial for not only developmental processes but also processes of diseases such as hypospadias and prostate cancer.
  • #Ryuma Haraguchi, Riko Kitazawa, Yuuki Imai, Sohei Kitazawa, #corresponding author
    Histochemistry and cell biology 149 4 365 - 373 2018年04月 [有り][有り]
     
    Longitudinal bone growth progresses by continuous bone replacement of epiphyseal cartilaginous tissue, known as "growth plate", produced by columnar proliferated- and differentiated-epiphyseal chondrocytes. The endochondral ossification process at the growth plate is governed by paracrine signals secreted from terminally differentiated chondrocytes (hypertrophic chondrocytes), and hedgehog signaling is one of the best known regulatory signaling pathways in this process. Here, to investigate the developmental relationship between longitudinal endochondral bone formation and osteogenic progenitors under the influence of hedgehog signaling at the growth plate, genetic lineage tracing was carried out with the use of Gli1CreERT2 mice line to follow the fate of hedgehog-signal-responsive cells during endochondral bone formation. Gli1CreERT2 genetically labeled cells are detected in hypertrophic chondrocytes and osteo-progenitors at the chondro-osseous junction (COJ); these progeny then commit to the osteogenic lineage in periosteum, trabecular and cortical bone along the developing longitudinal axis. Furthermore, in ageing bone, where longitudinal bone growth ceases, hedgehog-signal responsiveness and its implication in osteogenic lineage commitment is significantly weakened. These results show, for the first time, evidence of the developmental contribution of endochondral progenitors under the influence of epiphyseal chondrocyte-derived secretory signals in longitudinally growing bone. This study provides a precise outline for assessing the skeletal lineage commitment of osteo-progenitors in response to growth-plate-derived regulatory signals during endochondral bone formation.
  • Riko Kitazawa, Ryuma Haraguchi, Mana Fukushima, Sohei Kitazawa
    Histochemistry and cell biology 149 4 405 - 415 2018年04月 [有り][無し]
     
    Hard tissue homeostasis is regulated by the balance between bone formation by osteoblasts and bone resorption by osteoclasts. This physiologic process allows adaptation to mechanical loading and calcium homeostasis. Under pathologic conditions, however, this process is ill-balanced resulting in either over-resorption or over-formation of hard tissue. Local over-resorption by osteoclasts is typically observed in osteolytic metastases of malignancies, autoimmune arthritis, and giant cell tumor of bone (GCTB). In tumor-related local osteolysis, tumor-derived osteoclast-activating factors induce bone resorption not by directly acting on osteoclasts but by indirectly upregulating receptor activator of NFκB ligand (RANKL) on osteoblastic cells. Similarly, synovial tissue in the autoimmune arthritis model does overexpress RANKL and contains numerous osteoclast precursors, and like a landing craft, when it comes in contact with eroded bone surfaces, osteoclast precursors are immediately polarized to become mature osteoclasts, inducing rapidly progressive bone destruction at a late stage of the disease. GCTB, on the other hand, is a common primary bone tumor, usually arising at the metaphysis of the long bone in young adults. After the discovery of RANKL, the concept of GCTB as a tumor of RANKL-expressing stromal cells was established, and comprehensive exosome studies finally disclosed the causative single-point mutation at histone H3.3 (H3F3A) in stromal cells. Thus, osteolytic lesions under various pathological conditions are ultimately attributable to the overexpression of RANKL, which opens up a common, practical and useful therapeutic target for diverse osteolytic conditions.
  • Calmodulin-like 5(CALML5)の子宮頸部扁平上皮癌における発現制御
    上田 康雄, 北澤 理子, 福島 万奈, 近藤 武史, 原口 竜摩, 北澤 荘平
    日本病理学会会誌 107 1 388 - 388 (一社)日本病理学会 2018年04月 [有り][無し]
  • Saki Ito, Riko Kitazawa, Ryuma Haraguchi, Takeshi Kondo, Ayaka Ouchi, Yasuo Ueda, Sohei Kitazawa
    Diagnostic pathology 13 1 1 - 1 2018年01月 [有り][無し]
     
    BACKGROUND: A proper balance between the activator and the repressor form of GLI3, a zinc-finger transcription factor downstream of hedgehog signaling, is essential for proper development of various organs during development. Mutations in different domains of the GLI3 gene underlie several congenital diseases including Greig cephalopolysyndactyly syndrome (GCPS) and Pallister-Hall syndrome (PHS). CASE PRESENTATION: Here, we describe the case of an overlapped phenotype of these syndromes with agenesis of the gallbladder and the pancreas, bearing a c.2155 C > T novel likely pathogenic variant of GLI3 gene by missense point mutation causing p.P719S at the proteolytic cleavage site. CONCLUSIONS: Although agenesis of the gallbladder and the pancreas is uncommon in GLI3 morphopathy, a slight difference in the gradient or the balance between activator and repressor in this case may hinder sophisticated spatial and sequential hedgehog signaling that is essential for proper development of gallbladder and pancreas from endodermal buds.
  • #Ryuma Haraguchi, Riko Kitazawa, Aki Murashima, Gen Yamada, Sohei Kitazawa, #corresponding author
    Acta histochemica et cytochemica 50 4 127 - 133 2017年08月 [有り][無し]
     研究論文(学術雑誌) 
    In mammals, the müllerian duct (MD) is an embryonic tubular structure that gives rise to the female reproductive tract (FRT). The MD originates from the coelomic epithelium (CoE) and takes on a rostral to caudal shape to establish the primary structure of the FRT under the regulation of morphogenetic signals. During these developmental processes, the MD and its derivatives require proper regulation of the Wnt-signaling-pathway. Here, to investigate the developmental contribution of FRT primordia under the influence of the Wnt-signaling, genetic lineage tracing was carried out using TopCreER/Rosa-LacZ mice to follow the fate of Wnt-signal-responsive cells during reproductive tract formation. TopCreER-marked-LacZ+ cells, arising from the Wnt-signal-responsive progenitors in CoE, give rise to spatially restricted MD and the uterine luminal epithelium. Similarly, the progeny from LacZ+ mesenchymal cells surrounding the MD contribute to both the uterine smooth muscle and stroma. Furthermore, in males, the Wnt-signal-responsive MD mesenchyme develops into the epididymis. These results show, for the first time, evidence of the sequential involvement of reproductive tract progenitors under the influence of Wnt-signal throughout the developmental term. This study provides a precise outline for assessing the lineage relation between the reproductive tract and the cell fate of its primordia in a temporally regulated manner.
  • Nishi Y, Kitazawa R, Haraguchi R, Ouchi A, Ueda Y, Kamaoka Y, Yamamoto K, Todo Y, Miyaoka H, Kitazawa S
    Case reports in oncology 10 2 508 - 514 2017年05月 [有り][無し]
  • Ryuma Haraguchi, Riko Kitazawa, Kiyoshi Mori, Ryosuke Tachibana, Hiroshi Kiyonari, Yuuki Imai, Takaya Abe, Sohei Kitazawa
    Scientific reports 6 25198 - 25198 2016年04月 [有り][無し]
     
    sFRP4 is an extracellular Wnt antagonist that fine-tunes its signal activity by direct binding to Wnts. Bone fragility under oxidative stress by diabetes and aging is partly related to the suppression of the Wnt signal through upregulated sFRP4. Here, to explore the functions of sFRP4 as a balancer molecule in bone development and remodeling, we analyzed the sFRP4 knock-in mouse strain. X-gal and immunohistochemically stained signals in sFRP4-LacZ heterozygous mice were detectable in restricted areas, mostly in osteoblasts and osteoclasts, of the femoral diaphysis after neonatal and postnatal stages. Histological and μCT analyses showed increased trabecular bone mass with alteration of the Wnt signal and osteogenic activity in sFRP4 mutants; this augmented the effect of the buildup of trabecular bone during the ageing period. Our results indicate that sFRP4 plays a critical role in bone development and remodeling by regulating osteoblasts and osteoclasts, and that its functional loss prevents age-related bone loss in the trabecular bone area. These findings imply that sFRP4 functions as a key potential endogenous balancer of the Wnt signaling pathway by efficiently having direct influence on both bone formation and bone absorption during skeletal bone development and maintenance through remodeling.
  • Yuri Kameoka, Riko Kitazawa, Kanazu Ariasu, Ryosuke Tachibana, Yosuke Mizuno, Ryuma Haraguchi, Sohei Kitazawa
    Acta histochemica et cytochemica 48 4 115 - 24 2015年08月 [有り][無し]
     
    To explore the epigenetic mechanism that reactivates CDX2 (a homeobox transcription factor that serves as a tumor-suppressor gene) in intestinal-type gastric cancer during cancer progression, we examined the methylation status of the CDX2 gene promoter and the expression pattern of methyl-CpG binding protein-2 (MeCP2). From archives of the pathology records of surgically excised advanced stomach cancer cases in the Department of Molecular Pathology, Ehime University in a past decate (n=265), 10 cases of intestinal-type tubular adenocarcinoma, well-differentiated type (wel) with minor poorly-differentiated adenocarcinoma (por) components were selected. The expression pattern of CDX2, MUC2 and MeCP2 in these 10 cases was analyzed by immunohistochemistry. The cancerous and non-cancerous areas were selectively obtained by microdissection, and the methylation status of the CDX2 promoter of each area was assessed by methylation-specific polymerase chain reaction (MSP). In all 10 cases, CDX2 expression was clearly observed in the nucleus of the non-cancerous background of the intestinal metaplasic area, where the unmethylation pattern of the CDX2 gene promoter prevailed with reduced MeCP2 expression. In this metaplastic area, CDX2 expression was co-localized with its target gene, MUC2. CDX2 expression then disappeared from the deep invasive wel area. Reflecting the reduced CDX2 expression, microdissected samples from all the wel areas showed hypermethylation of the CDX2 gene promoter by MSP, with prominent MeCP2 expression. Interestingly, while hypermethylation of the CDX2 gene promoter was maintained in the por area in 8 of the 10 cases, CDX2 expression was restored in por areas where MeCP2 expression was markedly and selectively reduced. The other two cases, however, showed a constant MeCP2 expression level comparable to the surrounding deep invasive wel area with negative CDX2 expression. Therefore, gene silencing by hypermethylation may be overcome by the reduction of methyl-CpG binding proteins, resulting in apparent but non-functional reactivation of CDX2 as a mere molecular mark for gene silencing memory.
  • Ryuma Haraguchi, Riko Kitazawa, Sohei Kitazawa
    Cell and tissue research 359 2 503 - 512 2015年02月 [有り][無し]
     
    Endochondral bone formation is tightly regulated by the spatial and sequential expression of a series of transcription factors. To disclose the roles of TBX18, a member of the T-box transcription factor family, during endochondral bone formation, its spatial and temporal expression patterns were characterized in the limb skeletal region of the developing mouse together with those of established osteochondrogenic markers Sox9, Col2a1, and Runx2. TBX18 expression first appeared in condensed mesenchymal cells (chondro-progenitors) in embryonic-day-10.5 (E10.5) limb bud and was co-localized with Sox9 expression, whereas at E11.5 and E12.5, it became undetectable in mesenchymal cells committed to the chondrocyte lineage. From E13.5 to E18.5, TBX18 expression reappeared in chondrocytes, correlating strongly with Col2a1 expression; furthermore, low level TBX18 expression was found in the Runx2-positive perichondral osteoblastic cell lineage. At the postnatal stage, TBX18 expression was observed in epiphyseal chondrocytes and osteocytes within the lacunae of mature trabecular bone. On the assumption that such characteristic Tbx18 gene expression is epigenetically regulated during mouse limb development, we examined the methylation status of the CpG-island in the mouse Tbx18 gene by methylation-specific polymerase chain reaction. Hypermethylation of the Tbx18 gene promoter became evident at an early embryonic stage in TBX18-negative cells and then disappeared at a late embryonic stage in TBX18-positive cells. Therefore, the temporal suppression of Tbx18 gene expression by the hypermethylation of its promoter seems to trigger the differentiation of mesenchymal cells into hypertrophic chondrocytes in the early stages of endochondral ossification.
  • Nakagawa M, Kitazawa R, Kondo T, Ninomiya K, Okita M, Haraguchi R, Kitazawa S
    Virchows Archiv : an international journal of pathology 465 3 253 - 6 2014年09月 [有り][無し]
     研究論文(学術雑誌) 
    Duodenal gastric heterotopia (DGH) is a benign asymptomatic condition assumed to be of congenital origin. Since DGH is often associated with fundic gland polyps (FGPs) that frequently carry a somatic β-catenin gene mutation, we examined whether DGH, either sporadic or FGP-associated, is attributable to alterations of the Wnt/β-catenin pathway. Genetic analysis revealed frequent somatic β-catenin gene mutations in DGH; some of which showed the same mutation pattern as coexisting FGPs. All missense mutations were confined to codons 32, 33, and 37. No such mutations were observed, however, in any of the specimens from focal gastric foveolar metaplasia (GFM). Therefore, DGH is not a mere congenital lesion due to aberrant migration of normal gastric mucosa or a simple reactive metaplasia after regenerative stimuli of the duodenal mucosa, but a distinct condition based upon molecular genetic changes in the Wnt/β-catenin pathway.
  • Takafumi Watanabe, Riko Kitazawa, Yosuke Mizuno, Natsumi Kuwahara, Chizu Ito, Atsuro Sugita, Ryuma Haraguchi, Sohei Kitazawa
    Acta histochemica et cytochemica 47 3 125 - 31 2014年06月 [有り][無し]
     研究論文(学術雑誌) 
    Analysis of archival formalin-fixed, paraffin-embedded (FFPE) pathological specimens of three case of Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) and three cases of classical Hodgkin lymphoma (CHL) revealed that hypermethylation of the BOB.1 gene promoter was exclusively observed in CHL. A discrepancy was observed, however, between the methylation status of the BOB.1 gene promoter and its expression in the EBV-positive mixed cellular CHL (MCCHL). Since MCCHL lacks the typical B-cell phenotype even in the presence of abundant BOB.1 transcription factors, functional activity of BOB.1 may be lost or reduced by a mechanism other than epigenetic gene silencing. When some tumor-suppressor gene products have lost their biological function, impact or significance of derepression of such genes may be little. Therefore, when interpreting immunohistochemical results for diagnostic or research purposes, it must be borne in mind that apparent positive immunostaining can merely be the result of chromatin remodeling and that such transient expression often has little functional significance. Any apparent positive immunohistochemical result needs to be interpreted carefully with the help of the hypermethylation status as a molecular marker of gene silencing memory.
  • Shinichi Miyagawa, Masayo Harada, Daisuke Matsumaru, Kazuki Tanaka, Chie Inoue, Chiaki Nakahara, Ryuma Haraguchi, Shoko Matsushita, Kentaro Suzuki, Naomi Nakagata, Roy Chun-Laam Ng, Keiichi Akita, Vincent Chi-Hung Lui, Gen Yamada
    Cell Death Differ 21 6 990 - 997 2014年06月 [無し][無し]
     
    The cloaca is temporally formed and eventually divided by the urorectal septum (URS) during urogenital and anorectal organ development. Although congenital malformations, such as anorectal malformations (ARMs), are frequently observed during this process, the underlying pathogenic mechanisms remain unclear. β-Catenin is a critical component of canonical Wnt signaling and is essential for the regulation of cell differentiation and morphogenesis during embryogenesis. The expression of β-catenin is observed in endodermal epithelia, including URS epithelia. We modulated the β-catenin gene conditionally in endodermal epithelia by utilizing tamoxifen-inducible Cre driver line (Shh(CreERT2)). Both β-catenin loss- and gain-of-function (LOF and GOF) mutants displayed abnormal clefts in the perineal region and hypoplastic elongation of the URS. The mutants also displayed reduced cell proliferation in the URS mesenchyme. In addition, the β-catenin GOF mutants displayed reduced apoptosis and subsequently increased apoptosis in the URS epithelium. This instability possibly resulted in reduced expression levels of differentiation markers, such as keratin 1 and filaggrin, in the perineal epi
  • *Miyagawa S, *Harada M, *Matsumaru D, Tanaka K, Inoue C, Nakahara C, Haraguchi R, Matsushita S, Suzuki K, Nakagata N, Ng RC, Akita K, Lui VC, Yamada G, *Equally contributed first author
    Cell death and differentiation 21 6 990 - 997 2014年06月 [有り][無し]
  • Daisuke Matsumaru, #Ryuma Haraguchi, Anne M. Moon, Yoshihiko Satoh, Naomi Nakagata, Ken-ichi Yamamura, Naoki Takahashi, Sohei Kitazawa, Gen Yamada, # Equally contributed first author
    EUROPEAN JOURNAL OF HUMAN GENETICS 22 3 350 - 357 2014年03月 [有り][無し]
     研究論文(学術雑誌) 
    Although several syndromes include abnormalities of both the ventral body wall and external genitalia, the developmental bases of this correlation are largely unknown. Naturally occurring mutations in Aristaless-like 4 (Alx4, Strong's luxoid: Alx4(Lst)) have ventral body wall and pelvic girdle abnormalities. We sought to determine whether the development of the genital tubercle (GT) and its derivatives, the external genitalia, is affected by this mutation. We thus performed genetic and tissue labeling analyses in mutant mice. Alx4(Lst/Lst) mutants displayed hypoplasia of the dorsal GT and reduced expression of Fibronectin. We analyzed cell migration during GT formation by tissue labeling experiments and discovered that the cells located in the proximal segment of the umbilical cord (infra-umbilical mesenchyme) migrate toward the dorsal part of the GT. The Alx4(Lst/Lst) mutants also displayed augmented expression of Hh signal-related genes. Hence, we analyzed a series of combinatorial mutants for Alx4, Sonic hedgehog (Shh) and GLI-Kruppel family member 3 (Gli3). These phenotype-genotype analyses suggested a genetic interaction between Alx4 and Hh signaling during GT formation. Moreover, Hh gain-of-function mutants phenocopied some of these phenotypes. These observations reveal novel information regarding the pathogenic mechanisms of syndromic lower ventral body malformations, which are largely unknown.
  • Koto Fujiishi, Riko Kitazawa, Yusa Nagai, Takafumi Watanabe, Kenji Bando, Shinji Kobayashi, Yoshihiro Yakushijin, Ryuma Haraguchi, Sohei Kitazawa
    Virchows Archiv : an international journal of pathology 464 1 121 - 4 2014年01月 [有り][無し]
  • Mori K, Kitazawa R, Kondo T, Mori M, Hamada Y, Nishida M, Minami Y, Haraguchi R, Takahashi Y, Kitazawa S
    PloS one 9 7 e102797  2014年 [有り][無し]
     研究論文(学術雑誌) 
    In diabetics, methylglyoxal (MG), a glucose-derived metabolite, plays a noxious role by inducing oxidative stress, which causes and exacerbates a series of complications including low-turnover osteoporosis. In the present study, while MG treatment of mouse bone marrow stroma-derived ST2 cells rapidly suppressed the expression of osteotrophic Wnt-targeted genes, including that of osteoprotegerin (OPG, a decoy receptor of the receptor activator of NF-kappaB ligand (RANKL)), it significantly enhanced that of secreted Frizzled-related protein 4 (sFRP-4, a soluble inhibitor of Wnts). On the assumption that upregulated sFRP-4 is a trigger that downregulates Wnt-related genes, we sought out the molecular mechanism whereby oxidative stress enhanced the sFRP-4 gene. Sodium bisulfite sequencing revealed that the sFRP-4 gene was highly methylated around the sFRP-4 gene basic promoter region, but was not altered by MG treatment. Electrophoretic gel motility shift assay showed that two continuous CpG loci located five bases upstream of the TATA-box were, when methylated, a target of methyl CpG binding protein 2 (MeCP2) that was sequestered upon induction of 8-hydroxy-2-deoxyguanosine, a biomarker of oxidative damage to DNA. These in vitro data suggest that MG-derived oxidative stress (not CpG demethylation) epigenetically and rapidly derepress sFRP-4 gene expression. We speculate that under persistent oxidative stress, as in diabetes and during aging, osteopenia and ultimately low-turnover osteoporosis become evident partly due to osteoblastic inactivation by suppressed Wnt signaling of mainly canonical pathways through the derepression of sFRP-4 gene expression.
  • Komoda Munenori, Riko Kitazawa, Kenji Makita, Keisuke Yoshida, Miyuki Takeji, Yoshiko Soga, Mie Kurata, Ryuma Haraguchi, Sohei Kitazawa
    Diabetes research and clinical practice 100 2 e59-62 - 62 2013年05月 [有り][無し]
     
    Diabetes induces advanced glycation end products (AGEs) that per se are not only a major cause of oxidative stress but also reduce the plasticity of connective tissue by pathological collagen cross-linking. We describe a case of severe pulmonary hypertension manifesting as a major diabetic complication. Impaired pulmonary arteriolar plasticity attributed to pentosidine, together with increased circulation volume by hyperosmotic pressure and reduction in myocardial compliance by multiple patchy fibrosis, may contribute to the clinical manifestation of severe pulmonary hypertension.
  • Sann Sanda Khin, Riko Kitazawa, Kyaw Htet, Hla Min Htike, Than Than Yee, Myint Aung, Ryuma Haraguchi, Sohei Kitazawa
    Pathology international 63 3 193 - 4 2013年03月 [有り][無し]
  • Natsumi Kuwahara, Riko Kitazawa, Koto Fujiishi, Yusa Nagai, Ryuma Haraguchi, Sohei Kitazawa
    World journal of gastroenterology 19 8 1314 - 7 2013年02月 [有り][無し]
     
    Gastritis cystica profunda (GCP) is a rare condition caused by ectopic entrapment of gastric glands, probably secondary to the disruption of muscularis mucosae. GCP is often associated with gastric adenocarcinoma, and loss of the KCNE2 subunit from potassium channel complexes is considered a common primary target molecule leads to both GCP and malignancy. In this study, we, for the first time, analyzed the expression of KCNE2 in surgically excised tissue from human gastric cancer associated with GCP and confirmed that reduced KCNE2 expression correlates with disease formation.
  • Nakagawa M, Kitazawa R, Kuwahara N, Yoshida K, Haraguchi R, Kitazawa S
    Acta histochemica et cytochemica 46 1 19 - 24 2013年02月 [有り][無し]
     
    Molecular genetic analyses of archival formalin-fixed, paraffin-embedded (FFPE) pathological specimens taken at biopsy or autopsy, are occasionally compromised because the DNA molecules therein are inevitably degraded. Furthermore, since these tissue samples comprise various cell types, the analyses based on mixtures of such heterogeneous populations often fail to reflect the nature of the affected cells. In the present study, to elucidate the contribution of β-catenin gene mutation to the fundic gland polyp and the heterotopic gastric mucosa in the duodenum, we successfully introduced an agarose-bead mediated technique as an effectual tool for retrospective morphology-oriented genetic analyses. Microdissected samples were embedded in low-melting agarose, and directly treated with proteinase K. A fragment of the agarose-bead was used as a template for polymerase chain reaction to analyze β-catenin mutation. Of the six cases of heterotopic gastric mucosa in the duodenum associated with fundic gland polyps, one showed a common 1-bp missense mutation at codon 37 shared by both the fundic gland polyp and the heterotopic gastric mucosa. Alternatively, a 1-bp silent mutation at codon 33 and missense mutation at codon 32 were identified only in the heterotopic gastric mucosa. Agarose-bead mediated technique shows superior sensitivity to the previously described techniques and is an effectual tool for retrospective morphology-oriented genetic analyses using a large number of archival pathological samples stored for long periods in the pathology laboratory.
  • Kenji Makita, Riko Kitazawa, Shuho Semba, Koto Fujiishi, Miku Nakagawa, Ryuma Haraguchi, Sohei Kitazawa
    World journal of gastroenterology 19 4 536 - 41 2013年01月 [有り][無し]
     
    AIM: To examine how the expression of caudal type homebox transcription factor 2 (Cdx2) is regulated in the development of malignancy in Barrett's esophagus. METHODS: Cdx2, mucin (MUC) series (MUC2, MUC5AC and MUC6), p53 and E-cadherin expression in Barrett's esophagus and adenocarcinoma specimens were examined by immunostaining. Isolated clusters of cells from (1) MUC2 and Cdx2-positive intestinal metaplastic mucosa; (2) MUC5AC and MUC6-positive, and MUC2 and Cdx2-negative high-grade dysplasia (HD), or intramucosal adenocarcinoma (IMC); and (3) MUC5AC, MUC6 and Cdx2-positive poorly-differentiated invasive adenocarcinoma (PDA) were analyzed by methylation-specific polymerase chain reaction using sets of primers for detecting methylation status of the Cdx2 gene. RESULTS: Most of the non-neoplastic Barrett's esophageal mucosa showing intestinal-type metaplasia with or without low-grade dysplasia was positive for E-cadherin, MUC series and Cdx2, but negative for p53. A portion of the low-grade to HD was positive for E-cadherin, MUC5AC, MUC6 and p53, but negative for MUC2 and Cdx2. The definite IMC area was strongly positive for MUC5AC, MUC6 and p53, but negative for MUC2 and Cdx2. Methylation of the Cdx2 promoter was not observed in intestinal metaplasia, while hypermethylation of part of its promoter was observed in hot dipped and IMC. Hypermethylation of a large fraction of the Cdx2 promoter was observed in PDA. CONCLUSION: Cdx2 expression is restored irrespective of the methylation status of its promoter. Apparent positive immunohistochemical results can be a molecular mark for gene silencing memory.
  • Chihiro Ito, Riko Kitazawac, Kenji Makita, Takafumi Watanabe, Akihiro Toda, Ryuma Haraguchi, Shinji Tanaka, Sohei Kitazawa
    Journal of medical case reports 6 260 - 260 2012年08月 [有り][無し]
     
    INTRODUCTION: Verruciform xanthoma is a rare, benign lesion characterized by hyperkeratosis and aggregates of foam cell macrophages. Here, we describe a case of verruciform xanthoma on the scrotum, in which the immunohistochemical localization of monocyte chemoattractant protein-1, a chemokine of the C-C or beta family that has been shown to induce the recruitment of monocytes for injured tissue, was analyzed to determine which cells release chemoattractants for macrophages. CASE PRESENTATION: A 75-year-old Japanese man with a well-defined nodule on the left scrotum was admitted to the hospital. An excision biopsy revealed epidermal papillary proliferation with parakeratosis, hyperkeratosis, and infiltration of foam cell macrophages, whereby a pathological diagnosis of benign cutaneous verruciform xanthoma was made. Immunohistochemically, monocyte chemoattractant protein-1 was observed predominantly on cytokeratin AE1/AE3-positive differentiating keratinocytes in the prickle cell layer. However, while infiltrating macrophages were densely stained for monocyte chemoattractant protein-1, keratinocytes in the basal and parabasal layers were almost negative. CONCLUSIONS: We demonstrated that keratinocyte-derived monocyte chemoattractant protein-1 plays an important role in the establishment of particular histological features of verruciform xanthoma. However, in the present case, unlike in previous reports, monocyte chemoattractant protein-1 immunostaining in keratinocytes in the basal and parabasal layers was not prominent. We speculate that in the active phase of verruciform xanthoma, when continuous stimuli that release monocyte chemoattractant protein-1 from keratinocytes to the surrounding stromal area are present, the apparent immunostaining of monocyte chemoattractant protein-1 can be underestimated because of the void created by accelerated keratinocyte release from the cytoplasmic fraction.
  • 『技術講座』(病理)病理標本を用いたDNAシークエンスの方法と実際
    北澤荘平, 近藤武史, 中川みく, 藤石 琴, 学, 原口竜摩, 北澤理子
    検査と技術 40 1 24 - 29 2012年 [無し][無し]
  • Kentaro Suzuki, Yasuha Adachi, Tomokazu Numata, Shoko Nakada, Motoko Yanagita, Naomi Nakagata, Sylvia M Evans, Daniel Graf, Aris Economides, Ryuma Haraguchi, Anne M Moon, Gen Yamada
    PloS one 7 9 e43453  2012年 [有り][無し]
     
    Sirenomelia, also known as mermaid syndrome, is a developmental malformation of the caudal body characterized by leg fusion and associated anomalies of pelvic/urogenital organs including bladder, kidney, rectum and external genitalia. Most affected infants are stillborn, and the few born alive rarely survive beyond the neonatal period. Despite the many clinical studies of sirenomelia in humans, little is known about the pathogenic developmental mechanisms that cause the complex array of phenotypes observed. Here, we provide new evidences that reduced BMP (Bone Morphogenetic Protein) signaling disrupts caudal body formation in mice and phenocopies sirenomelia. Bmp4 is strongly expressed in the developing caudal body structures including the peri-cloacal region and hindlimb field. In order to address the function of Bmp4 in caudal body formation, we utilized a conditional Bmp4 mouse allele (Bmp4(flox/flox)) and the Isl1 (Islet1)-Cre mouse line. Isl1-Cre is expressed in the peri-cloacal region and the developing hindimb field. Isl1Cre;Bmp4(flox/flox) conditional mutant mice displayed sirenomelia phenotypes including hindlimb fusion and pelvic/urogenital organ dysgenesis. Genetic lineage analyses indicate that Isl1-expressing cells contribute to both the aPCM (anterior Peri-Cloacal Mesenchyme) and the hindlimb bud. We show Bmp4 is essential for the aPCM formation independently with Shh signaling. Furthermore, we show Bmp4 is a major BMP ligand for caudal body formation as shown by compound genetic analyses of Bmp4 and Bmp7. Taken together, this study reveals coordinated development of caudal body structures including pelvic/urogenital organs and hindlimb orchestrated by BMP signaling in Isl1-expressing cells. Our study offers new insights into the pathogenesis of sirenomelia.
  • Ryuma Haraguchi, Daisuke Matsumaru, Naomi Nakagata, Shinichi Miyagawa, Kentaro Suzuki, Sohei Kitazawa, Gen Yamada
    PloS one 7 7 e42245  2012年 [有り][無し]
     
    BACKGROUND: Congenital diseases of the urinary tract are frequently observed in infants. Such diseases present a number of developmental anomalies such as hydroureter and hydronephrosis. Although some genetically-modified mouse models of growth factor signaling genes reproduce urinary phenotypes, the pathogenic mechanisms remain obscure. Previous studies suggest that a portion of the cells in the external genitalia and bladder are derived from peri-cloacal mesenchymal cells that receive Hedgehog (Hh) signaling in the early developmental stages. We hypothesized that defects in such progenitor cells, which give rise to urinary tract tissues, may be a cause of such diseases. METHODOLOGY/PRINCIPAL FINDINGS: To elucidate the pathogenic mechanisms of upper urinary tract malformations, we analyzed a series of Sonic hedgehog (Shh) deficient mice. Shh(-/-) displayed hydroureter and hydronephrosis phenotypes and reduced expression of several developmental markers. In addition, we suggested that Shh modulation at an early embryonic stage is responsible for such phenotypes by analyzing the Shh conditional mutants. Tissue contribution assays of Hh-responsive cells revealed that peri-cloacal mesenchymal cells, which received Hh signal secreted from cloacal epithelium, could contribute to the ureteral mesenchyme. Gain- and loss-of-functional mutants for Hh signaling revealed a correlation between Hh signaling and Bone morphogenetic protein (Bmp) signaling. Finally, a conditional ablation of Bmp receptor type IA (BmprIA) gene was examined in Hh-responsive cell lineages. This system thus made it possible to analyze the primary functions of the growth factor signaling relay. The defective Hh-to-Bmp signaling relay resulted in severe urinary tract phenotypes with a decrease in the number of Hh-responsive cells. CONCLUSIONS/SIGNIFICANCE: This study identified the essential embryonic stages for the pathogenesis of urinary tract phenotypes. These results suggested that Hh-responsive mesenchymal Bmp signaling maintains the population of peri-cloacal mesenchyme cells, which is essential for the development of the ureter and the upper urinary tract.
  • Yusa Nagai, Riko Kitazawa, Miku Nakagawa, Munenori Komoda, Takeshi Kondo, Ryuma Haraguchi, Sohei Kitazawa
    Case reports in pathology 2012 613180 - 613180 2012年 [有り][無し]
     
    Introduction. Multiple system atrophy (MSA) is a rare and severe adult-onset, sporadic, and progressive neurodegenerative disorder. Here, we describe an autopsy case of MSA in a long-term professional painter. Although typical glial cytoplasmic inclusion (GCI) was not observed in a routine histological examination, strong α-synuclein immunostaining in the nucleus confirmed the diagnosis of MSA. Case Presentation. A 48-year-old Japanese man with a long occupational history of professional painter was sent to the emergency room, where he died of multiple organ failure. The patient had suffered tremors and inarticulateness at age 28, developed diabetes at 42 and was diagnosed with spinocerebellar degeneration at 46. A histopathological examination showed severe neuronal loss, gliosis, and tissue rarefaction in the paleostriatum, striate body of the substantia nigra, the pons, and the olivary nucleus of the upper medulla oblongata, intermediolateral of the spinal gray matter (sacral region). α-synuclein-positive GCI in oligodendroglia was occurred in the cerebral cortex, the midbrain, the medulla oblongata, and the spinal cord. These findings confirmed the presence of multiple-system atrophy (OPCA+SDS). Conclusion. Although the pathogenesis of MSA is still unclear, prolonged, and extensive exposure to organic solvents, together with a hyperglycemic morbidity attributed to diabetes, may have contributed to the onset and clinical course of the present case.
  • Shinichi Miyagawa, Daisuke Matsumaru, Aki Murashima, Akiko Omori, Yoshihiko Satoh, Ryuma Haraguchi, Jun Motoyama, Taisen Iguchi, Naomi Nakagata, Chi-Chung Hui, Gen Yamada
    Endocrinology 152 7 2894 - 903 2011年07月 [有り][無し]
     研究論文(学術雑誌) 
    During embryogenesis, sexually dimorphic organogenesis is achieved by hormones produced in the gonad. The external genitalia develop from a single primordium, the genital tubercle, and their masculinization processes depend on the androgen signaling. In addition to such hormonal signaling, the involvement of nongonadal and locally produced masculinization factors has been unclear. To elucidate the mechanisms of the sexually dimorphic development of the external genitalia, series of conditional mutant mouse analyses were performed using several mutant alleles, particularly focusing on the role of hedgehog signaling pathway in this manuscript. We demonstrate that hedgehog pathway is indispensable for the establishment of male external genitalia characteristics. Sonic hedgehog is expressed in the urethral plate epithelium, and its signal is mediated through glioblastoma 2 (Gli2) in the mesenchyme. The expression level of the sexually dimorphic genes is decreased in the glioblastoma 2 mutant embryos, suggesting that hedgehog signal is likely to facilitate the masculinization processes by affecting the androgen responsiveness. In addition, a conditional mutation of Sonic hedgehog at the sexual differentiation stage leads to abnormal male external genitalia development. The current study identified hedgehog signaling pathway as a key factor not only for initial development but also for sexually dimorphic development of the external genitalia in coordination with androgen signaling.
  • Khin SS, Kitazawa R, Kondo T, Idei Y, Fujimoto M, Haraguchi R, Mori K, Kitazawa S
    Cancers 3 1 982 - 93 2011年03月 [有り][無し]
     
    Epigenetic alterations in cancer, especially DNA methylation and histone modification, exert a significant effect on the deregulated expression of cancer-related genes and lay an epigenetic pathway to carcinogenesis and tumor progression. Global hypomethylation and local hypermethylation of CpG islands in the promoter region, which result in silencing tumor suppressor genes, constitute general and major epigenetic modification, the hallmark of the neoplastic epigenome. Additionally, methylation-induced gene silencing commonly affects a number of genes and increases with cancer progression. Indeed, cancers with a high degree of methylation (CpG island methylator phenotype/CIMP) do exist and represent a distinct subset of certain cancers including colorectal, bladder and kidney. On the other hand, signals from the microenvironment, especially those from transforming growth factor-β (TGF-β), induce targeted de novo epigenetic alterations of cancer-related genes. While TGF-β signaling has been implicated in two opposite roles in cancer, namely tumor suppression and tumor promotion, its deregulation is also partly induced by epigenetic alteration itself. Although the epigenetic pathway to carcinogenesis and cancer progression has such reciprocal complexity, the important issue is to identify genes or signaling pathways that are commonly silenced in various cancers in order to find early diagnostic and therapeutic targets. In this review, we focus on the epigenetic alteration by DNA methylation and its role in molecular modulations of the TGF-β signaling pathway that cause or underlie altered cancer-related gene expression in both phases of early carcinogenesis and late cancer progression.
  • Daisuke Matsumaru, Ryuma Haraguchi, Shinichi Miyagawa, Jun Motoyama, Naomi Nakagata, Frits Meijlink, Gen Yamada
    PloS one 6 1 e16260  2011年01月 [有り][無し]
     研究論文(学術雑誌) 
    BACKGROUND: An omphalocele is one of the major ventral body wall malformations and is characterized by abnormally herniated viscera from the body trunk. It has been frequently found to be associated with other structural malformations, such as genitourinary malformations and digit abnormalities. In spite of its clinical importance, the etiology of omphalocele formation is still controversial. Hedgehog (Hh) signaling is one of the essential growth factor signaling pathways involved in the formation of the limbs and urogenital system. However, the relationship between Hh signaling and ventral body wall formation remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: To gain insight into the roles of Hh signaling in ventral body wall formation and its malformation, we analyzed phenotypes of mouse mutants of Sonic hedgehog (Shh), GLI-Kruppel family member 3 (Gli3) and Aristaless-like homeobox 4 (Alx4). Introduction of additional Alx4(Lst) mutations into the Gli3(Xt/Xt) background resulted in various degrees of severe omphalocele and pubic diastasis. In addition, loss of a single Shh allele restored the omphalocele and pubic symphysis of Gli3(Xt/+); Alx4(Lst/Lst) embryos. We also observed ectopic Hh activity in the ventral body wall region of Gli3(Xt/Xt) embryos. Moreover, tamoxifen-inducible gain-of-function experiments to induce ectopic Hh signaling revealed Hh signal dose-dependent formation of omphaloceles. CONCLUSIONS/SIGNIFICANCE: We suggest that one of the possible causes of omphalocele and pubic diastasis is ectopically-induced Hh signaling. To our knowledge, this would be the first demonstration of the involvement of Hh signaling in ventral body wall malformation and the genetic rescue of omphalocele phenotypes.
  • Motowo Nabeta, Yasuhito Abe, Ryuma Haraguchi, Katsumi Kito, Yasuki Kusanagi, Masaharu Ito
    Fertility and sterility 94 7 2552 - 7 2010年12月 [有り][無し]
     
    OBJECTIVE: To establish a novel serum marker for endometriosis, serum autoantibodies (autoAbs) were investigated using a proteomic approach. DESIGN: Retrospective study. SETTING: Departments of Molecular Pathology and Obstetrics and Gynecology in Ehime University and University Hospital. PATIENT(S): Sixty-nine patients with endometriosis, 38 disease control patients without endometriosis, and 44 healthy volunteers. INTERVENTION(S): Autoantibodies in sera of endometriotic patients and healthy controls were investigated using a human fibroblast cell line, two-dimensional gel electrophoresis, and Western blotting. Proteins in reacted spots were identified using MALDI time of flight mass spectrometry with MASCOT analysis. ELISAs were established using recombinant proteins, and autoAb-titers were estimated in sera of endometriotic patients and controls. MAIN OUTCOME MEASURE(S): Identification of serum autoAb useful for diagnosis of endometriosis. RESULT(S): Several autoAbs were identified. ELISAs were established and serum autoAb titers were estimated. Among those identified, anti-PDIK1L-autoAb levels were significantly elevated in endometriotic patients. Sensitivity (59.4%) and accuracy (72.8%) of serum anti-PDIK1L-autoAb assay were better than those of serum CA125 levels (36.2% and 62.9%, respectively) in diagnosis of endometriosis. Additionally, anti-PDIK1L-autoAb could detect endometriotic patients in early stages. CONCLUSION(S): Serum anti-PDIK1L-autoAb can be a new serum marker for the diagnosis of endometriosis. This study validates further clinical evaluation of this novel marker.
  • [Lymphotoxin (TNF-beta)].
    Yuki Takaoka, Yasuhito Abe, Ryuma Haraguchi, Katsumi Kito
    Nihon rinsho. Japanese journal of clinical medicine 68 Suppl 7 93 - 5 2010年07月 [有り][無し]
  • Mylah Villacorte, Kentaro Suzuki, Katsuhiko Hayashi, Susana Chuva de Sousa Lopes, Ryuma Haraguchi, Makoto M Taketo, Naomi Nakagata, Gen Yamada
    Biochemical and biophysical research communications 391 4 1653 - 7 2010年01月 [有り][無し]
     
    Digit and interdigit (D/ID) development is one of the important research fields in molecular developmental biology. Interdigital cell death (ICD) is a morphogenetic event which has been considered as an essential process for D/ID formation. Although some growth factors including Bmp and Fgf signaling can modulate ICD, growth factor crosstalk regulating ICD is poorly understood. Wnt canonical pathway and Bmp signal crosstalk has been considered as the essential growth factor crosstalk in organogenesis. To elucidate the crosstalk to regulate the D/ID formation, we analyzed conditional mutant mice with limb bud ectoderm expressing constitutively activated beta-catenin signaling. We showed that modulation of Wnt/beta-catenin signal in the limb ectoderm including the AER regulates ID apoptosis. We also demonstrated that Wnt/beta-catenin signaling in the ectoderm can positively regulate Fgf8 possibly antagonizing the epithelial derived Bmp signaling. Human birth defects for digit abnormalities have been known to be affected by multiple parameters. Elucidation of the potential mechanisms underlying such D/ID development is an urgent medical issue to be solved. This work would be one of the first studies showing essential growth factor cascades in the D/ID formation.
  • Hedgehog,Wnt,FGFの三大増殖因子の相互作用:器官が伸長する(大きくなる)ために どのようなリレーが必要か
    宮川信一, 原田理代, 原口竜摩, 鈴木堅太郎, 中原千彰, 松丸大輔, 金子武人, 中潟直己, 山田 源
    細胞工学 29 2 188 - 189 2010年 [無し][無し]
  • 自己抗体のプロテオーム解析
    阿部康人, 鷹岡友紀, 原口竜摩, 木藤克己, 植田規史
    病理と臨床 28 518 - 523 2010年 [無し][無し]
  • Shinichi Miyagawa, Anne Moon, Ryuma Haraguchi, Chie Inoue, Masayo Harada, Chiaki Nakahara, Kentaro Suzuki, Daisuke Matsumaru, Takehito Kaneko, Isao Matsuo, Lei Yang, Makoto M Taketo, Taisen Iguchi, Sylvia M Evans, Gen Yamada
    Development (Cambridge, England) 136 23 3969 - 78 2009年12月 [有り][無し]
     
    Embryonic appendicular structures, such as the limb buds and the developing external genitalia, are suitable models with which to analyze the reciprocal interactions of growth factors in the regulation of outgrowth. Although several studies have evaluated the individual functions of different growth factors in appendicular growth, the coordinated function and integration of input from multiple signaling cascades is poorly understood. We demonstrate that a novel signaling cascade governs formation of the embryonic external genitalia [genital tubercle (GT)]. We show that the dosage of Shh signal is tightly associated with subsequent levels of Wnt/beta-catenin activity and the extent of external genitalia outgrowth. In Shh-null mouse embryos, both expression of Wnt ligands and Wnt/beta-catenin signaling activity are downregulated. beta-catenin gain-of-function mutation rescues defective GT outgrowth and Fgf8 expression in Shh-null embryos. These data indicate that Wnt/beta-catenin signaling in the distal urethral epithelium acts downstream of Shh signaling during GT outgrowth. The current data also suggest that Wnt/beta-catenin regulates Fgf8 expression via Lef/Tcf binding sites in a 3' conserved enhancer. Fgf8 induces phosphorylation of Erk1/2 and cell proliferation in the GT mesenchyme in vitro, yet Fgf4/8 compound-mutant phenotypes indicate dispensable functions of Fgf4/8 and the possibility of redundancy among multiple Fgfs in GT development. Our results provide new insights into the integration of growth factor signaling in the appendicular developmental programs that regulate external genitalia development.
  • Nabeta M, Abe Y, Kagawa L, Haraguchi R, Kito K, Ueda N, Sugita A, Yokoyama M, Kusanagi Y, Ito M
    Proteomics. Clinical applications 3 10 1201 - 10 2009年10月 [有り][無し]
     
    Diagnosis of endometriosis needs invasive maneuvers. New serum marker that possesses both high sensitivity and high specificity has long been desired. To establish novel serum marker for endometriosis, serum autoantibodies (autoAbs) were investigated using proteomic approach. AutoAbs in sera of endometriotic patients and healthy controls were analyzed using a mesothelial cell line, 2-DE and Western blotting. Proteins in reacted spots were identified using MALDI TOF-MS with MASCOT analysis. ELISAs were established using recombinant proteins and autoAb-titers were estimated in sera of endometriotic patients, disease and healthy controls. Several autoAbs were identified. Anti-α-enolase (Eno1)-autoAb levels in endometriotic patients were significantly elevated compared with both healthy and disease controls. Sensitivity and specificity of serum anti-Eno1-autoAb was nearly comparable to serum CA125. When anti-Eno1-autoAb and CA125 assays were combined, diagnostic sensitivity and accuracy improved. Serum anti-Eno1-autoAb can be a new serum endometriotic marker and it is useful as a supplement assay for CA125. This study validates further clinical evaluation of this novel marker.
  • Shinichi Miyagawa, Yoshihiko Satoh, Ryuma Haraguchi, Kentaro Suzuki, Taisen Iguchi, Makoto M Taketo, Naomi Nakagata, Takahiro Matsumoto, Ken-ichi Takeyama, Shigeaki Kato, Gen Yamada
    Molecular endocrinology (Baltimore, Md.) 23 6 871 - 80 2009年06月 [有り][無し]
     
    In most mammals, the sexually dimorphic development of embryos is typically achieved by the differentiation of the external genitalia. Hence, the sexual distinction of mammalian newborns is based on the external genital structure. Although it was shown in the 1940s and 1950s that androgen from the testes establishes the male sexual characteristics, the involvement of nongonadal and locally produced masculine effectors remains totally unknown. It is noteworthy that the disorders of fetal masculinization, including hypospadias, one of the most frequent birth defects, occur at a high frequency. Furthermore, their causative factors remain unclear. In this study, the involvement of the coordinated actions of androgen and the growth factor systems was genetically analyzed for the first time on mammalian reproductive organ formation. The results demonstrated that the Wnt/beta-catenin pathway is indispensable masculine factor for the external genital development. The bilateral mesenchymal region adjacent to the urethral plate epithelium displayed a sexually dimorphic activity of Wnt/beta-catenin signaling. Loss- and gain-of-function beta-catenin mutants displayed altered sexual development of the external genitalia. These results indicate the novel functions of the Wnt/beta-catenin pathway as a locally expressed masculine effector. This could be the first genetic study analyzing the roles of the genetic interactions between androgen and locally expressed growth factor signaling during the development of reproductive organs. These results also shed new insight on the reproductive genetics and the causative factors of genital disorders.
  • 高等哺乳類における泌尿生殖系器官の分子発生基盤の解明
    原口竜摩, 山田 源, 鍋田基生, 木藤克己, 阿部康人, 植田規史
    愛媛医学 23 3 127 - 131 2009年 [無し][無し]
     研究論文(学術雑誌)
  • Kentaro Suzuki, Ryuma Haraguchi, Tsutomu Ogata, Ottavia Barbieri, Olinda Alegria, Maxence Vieux-Rochas, Naomi Nakagata, Masataka Ito, Alea A Mills, Takeshi Kurita, Giovanni Levi, Gen Yamada
    European journal of human genetics : EJHG 16 1 36 - 44 2008年01月 [有り][無し]
     
    Urogenital birth defects are one of the common phenotypes observed in hereditary human disorders. In particular, limb malformations are often associated with urogenital developmental abnormalities, as the case for Hand-foot-genital syndrome displaying similar hypoplasia/agenesis of limbs and external genitalia. Split-hand/split-foot malformation (SHFM) is a syndromic limb disorder affecting the central rays of the autopod with median clefts of the hands and feet, missing central fingers and often fusion of the remaining ones. SHFM type 1 (SHFM1) is linked to genomic deletions or rearrangements, which includes the distal-less-related homeogenes DLX5 and DLX6 as well as DSS1. SHFM type 4 (SHFM4) is associated with mutations in p63, which encodes a p53-related transcription factor. To understand that SHFM is associated with urogenital birth defects, we performed gene expression analysis and gene knockout mouse model analyses. We show here that Dlx5, Dlx6, p63 and Bmp7, one of the p63 downstream candidate genes, are all expressed in the developing urethral plate (UP) and that targeted inactivation of these genes in the mouse results in UP defects leading to abnormal urethra formation. These results suggested that different set of transcription factors and growth factor genes play similar developmental functions during embryonic urethra formation. Human SHFM syndromes display multiple phenotypes with variations in addition to split hand foot limb phenotype. These results suggest that different genes associated with human SHFM could also be involved in the aetiogenesis of hypospadias pointing toward a common molecular origin of these congenital malformations.
  • 連携して器官を発生させる ヘッジホッグシグナルによる骨盤内外器官群の協調発生機構
    原口 竜摩, 佐藤 義彦, 宮川 信一, 松丸 大輔, 中潟 直己, 山田 源
    細胞工学 26 3 296 - 297 (株)学研メディカル秀潤社 2007年02月 [有り][無し]
  • Ryuma Haraguchi, Jun Motoyama, Hiroshi Sasaki, Yoshihiko Satoh, Shinichi Miyagawa, Naomi Nakagata, Anne Moon, Gen Yamada
    Development (Cambridge, England) 134 3 525 - 33 2007年02月 [有り][無し]
     
    The urogenital and reproductive organs, including the external genitalia, bladder and urethra, develop as anatomically aligned organs. Descriptive and experimental embryology suggest that the cloaca, and its derivative, the urogenital sinus, contribute to the formation of these organs. However, it is unknown how the primary tissue lineages in, and adjacent to, the cloaca give rise to the above organs, nor is bladder formation understood. While it is known that sonic hedgehog (Shh) is expressed by the cloacal epithelia, the developmental programs that regulate and coordinate the formation of the urogenital and reproductive organs have not been elucidated. Here we report that Shh mutant embryos display hypoplasia of external genitalia, internal urethra (pelvic urethra) and bladder. The importance of Shh signaling in the development of bladder and external genitalia was confirmed by analyzing a variety of mutant mouse lines with defective hedgehog signaling. By genetically labeling hedgehog-responding tissue lineages adjacent to the cloaca and urogenital sinus, we defined the contribution of these tissues to the bladder and external genitalia. We discovered that development of smooth muscle myosin-positive embryonic bladder mesenchyme requires Shh signaling, and that the bladder mesenchyme and dorsal (upper) external genitalia derive from Shh-responsive peri-cloacal mesenchyme. Thus, the mesenchymal precursors for multiple urogenital structures derive from peri-cloacal mesenchyme and the coordination of urogenital organ formation from these precursors is orchestrated by Shh signals.
  • 連携して器官を発生させる:ヘッジホッグシグナルによる骨盤内外器官群の協調発生機構
    原口竜摩, 佐藤義彦, 宮川信一, 松丸大輔, 中潟直己, 山田 源
    細胞工学 22 3 874 - 876 2007年 [無し][無し]
  • Yoshihiko Satoh, #Ryuma Haraguchi, Tracy J Wright, Suzanne L Mansour, Juha Partanen, Mohammad K Hajihosseini, Veraragavan P Eswarakumar, Peter Lonai, Gen Yamada, # Equally contributed first author
    Anatomy and embryology 208 6 479 - 86 2004年09月 [有り][無し]
     
    Members of the fibroblast growth factor (FGF) family play diverse roles during the development and patterning of various organs. In human and mice, 22 FGFs and four receptors derived from several splice variants are present. Redundant expression and function of FGF genes in organogenesis have been reported, but their roles in embryonic external genitalia, genital tubercle (GT), development have not been studied in detail. To address the role of FGF during external genitalia development, we have analyzed the expression of FGF genes (Fgf8, 9, 10) and receptor genes (Fgfr1, r2IIIb, r2IIIc) in GT of mice. Furthermore, Fgf10 and Fgfr2IIIb mutant mice were analyzed to elucidate their roles in embryonic external genitalia development. Fgfr2IIIb was expressed in urethral plate epithelium during GT development. Fgfr2IIIb mutant mice display urethral dysmorphogenesis. Marker gene analysis for urethral plate and bilateral mesenchymal formation suggests the existence of epithelial-mesenchymal interaction during urethral morphogenesis. Therefore, FGF10/FGFR2IIIb signals seem to constitute a developmental cascade for such morphogenesis.
  • マウス外生殖器原基(生殖結節)に見られる伸長制御メカニズム
    鈴木堅太郎, 神川真美, 尾木秀直, 原口竜摩, 荻野由紀子, 山田 源
    細胞工学 19 6 874 - 876 2004年 [無し][無し]
  • K Suzuki, D Bachiller, YPP Chen, M Kamikawa, H Ogi, R Haraguchi, Y Ogino, Y Minami, Y Mishina, K Ahn, EB Crenshaw, G Yamada
    DEVELOPMENT 130 25 6209 - 6220 2003年12月 [有り][無し]
     
    Extra-corporal fertilization depends on the formation of copulatory organs: the external genitalia. Coordinated growth and differentiation of the genital tubercle (GT), an embryonic anlage of external genitalia, generates a proximodistally elongated structure suitable for copulation, erection, uresis and ejaculation. Despite recent progress in molecular embryology, few attempts have been made to elucidate the molecular developmental processes of external genitalia formation. Bone morphogenetic protein genes (Bmp genes) and their antagonists were spatiotemporally expressed during GT development. Exogenously applied BMP increased apoptosis of GT and inhibited its outgrowth. It has been shown that the distal urethral epithelium (DUE), distal epithelia marked by the Fgf8 expression, may control the initial GT outgrowth. Exogenously applied BMP4 downregulated the expression of Fgf8 and Wnt5a, concomitant with increased apoptosis and decreased cell proliferation of the GT mesenchyme. Furthermore, noggin mutants and Bmpr1a conditional mutant mice displayed hypoplasia and hyperplasia of the external genitalia respectively. noggin mutant mice exhibited downregulation of Wnt5a and Fgf8 expression with decreased cell proliferation. Consistent with such findings; Wnt5a mutant mice displayed GT agenesis with decreased cell proliferation. By contrast, Bmpr1a mutant mice displayed decreased apoptosis and augmented Fgf8 expression in the DUE associated with GT hyperplasia. These results suggest that some of the Bmp genes could negatively affect proximodistally oriented outgrowth of GT with regulatory functions on cell proliferation and apoptosis. The DUE region can be marked only until 14.0 dpc (days post coitum) in mouse development, while GT outgrowth continues thereafter. Possible signaling crosstalk among the whole distal GT regions were also investigated.
  • Unique functions of Sonic hedgehog signaling during external genitalia development
    R Haraguchi, R Mo, CC Hui, J Motoyama, S Makino, T Shiroishi, W Gaffield, G Yamada
    DEVELOPMENT 128 21 4241 - 4250 2001年11月 [有り][無し]
     研究論文(学術雑誌) 
    Coordinated growth and differentiation of external genitalia generates a proximodistally elongated structure suitable for copulation and efficient fertilization. The differentiation of external genitalia incorporates a unique process, i.e. the formation of the urethral plate and the urethral tube. Despite significant progress in molecular embryology, few attempts have been made to elucidate the molecular developmental processes for external genitalia. The sonic hedgehog (Shh) gene and its signaling genes have been found to be dynamically expressed during murine external genitalia development. Functional analysis by organ culture revealed that Shh could regulate mesenchymally expressed genes, patched 1 (Ptch1), bone morphogenetic protein 4 (Bmp4), Hoxd13 and fibroblast growth factor 10 (Fgf10), in the anlage: the genital tubercle (GT). Activities of Shh for both GT outgrowth and differentiation were also demonstrated. Shh(-/-) mice displayed complete GT agenesis, which is compatible with such observations. Furthermore, the regulation of apoptosis during GT formation was revealed for the first time. Increased cell death and reduced cell proliferation of the Shh(-/-) mice GT were shown. A search for alterations of Shh downstream gene expression identified a dramatic shift of Binp4 gene expression from the mesenchyme to the epithelium of the Shh mutant before GT outgrowth. Regulation of mesenchymal Fgf10 gene expression by the epithelial Shh was indicated during late GT development. These results suggest a dual mode of Shh function, first by the regulation of initiating GT outgrowth, and second, by subsequent GT differentiation.
  • External genitalia formation - Role of fibroblast growth factor, retinoic acid signaling, and distal urethral epithelium
    Y Ogino, K Suzuki, R Haraguchi, Y Satoh, P Dolle, G Yamada
    ENVIRONMENTAL HORMONES: THE SCIENTIFIC BASIS OF ENDOCRINE DISRUPTION 948 13 - 31 2001年 [有り][無し]
     研究論文(学術雑誌) 
    The process of fetal external genitalia development might be divided into two processes. The first process accomplishes the initial outgrowth of the anlage, genital tubercle (GT). Previous analysis suggests that the distal urethral epithelium (DUE) of the GT, the Fgf8-expressing region, regulates the, outgrowth of the GT. The second process eventually generates the sexually dimorphic development of the external genitalia, which is dependent on the action of steroid hormones. Several key genes, for example, RARs, RXRs, RALDH2, and CYP26, were dynamically expressed during GT development. The teratogenic dose of RA at 9.0 d.p.c. induced a drastic malformation of the urethral plate during GT formation, but did not show gross abnormalities in its outgrowth. In RA-treated embryos, Fgf8 expression was still detected in the, distal GT regions. Possible regulatory roles of the FGF and RA signaling systems in external genitalia formation are discussed.
  • 外性器形成の分子メカニズム
    荻野由紀子, 原口竜摩, 加藤洋教, 山田 源
    医学のあゆみ 199 13 1083 - 1089 2001年 [無し][無し]
  • Molecular analysis of external genitalia formation: the role of fibroblast growth factor (Fgf) genes during genital tubercle formation
    R Haraguchi, K Suzuki, R Murakami, M Sakai, M Kamikawa, M Kengaku, K Sekine, H Kawano, S Kato, N Ueno, G Yamada
    DEVELOPMENT 127 11 2471 - 2479 2000年06月 [有り][無し]
     研究論文(学術雑誌) 
    The molecular mechanisms underlying the development of the external genitalia in mammals have been very little examined. Recent gene knockout studies have suggested that the developmental processes of its anlage, the genital tubercle (GT), have much in common with those of limb buds. The Fgf genes have been postulated as regulating several downstream genes during organogenesis. Fgf8 was expressed in the distal urethral plate epithelium of the genital tubercle (GT) together with other markers such as the Msx1, Fgf10, Hoxd13 and Bmp4 expressed in the mesenchyme. To analyze the role of the FGF system during GT formation, an in vitro organ culture system was utilized. It is suggested that the distal urethral plate epithelium of GT, the Fgf8-expressing region, regulates the outgrowth of GT. Ectopic application of FGF8 beads to the murine GT induced mesenchymal gene expression, and also promoted the outgrowth of the GT. Experiments utilizing anti-FGF neutralizing antibody suggested a growth-promoting role for FGF protein(s) in GT outgrowth. In contrast, despite its vital role during limb-bud formation, Fgf10 appears not to be primarily essential for initial outgrowth of GT, as extrapolated from Fgf10(-/-) GTs, However, the abnormal external genitalia development of Fgf10(-/-) perinatal mice suggested the importance of Fgf10 in the development of the glans penis and the glans clitoridis. These results suggest that the FGF system is a key element in orchestrating GT development.
  • 発生・分化とホメオボックス遺伝子咽頭胚期の顔面-頭部形成:goosecoid遺伝子を中心にして
    原口竜摩, 小松義広, 中村誠司, 鈴木堅太郎, 坂井美保, 宮戸健二, 矢野正二郎, 山田 源
    生体の科学 49 6 581 - 587 2000年 [無し][無し]
  • 外性器形成過程の分子的解析
    原口竜摩, 荻野由紀子, 神川真美, 鈴木堅太郎, 長谷川太郎, 一鬼 勉, 山田 源
    実験医学 18 6 752 - 758 2000年 [無し][無し]
  • 外性器形成過程の解析
    原口竜摩, 神川真美, 鈴木堅太郎, 荻野由紀子, 竹田直樹, 佐藤義彦, 一鬼 勉, 村上柳太郎, 山田 源
    細胞工学 19 6 874 - 876 2000年 [無し][無し]
  • Middle ear defects associated with the double knock out mutation of murine goosecoid and Msx1 genes
    S Kuratani, Satokata, I, M Blum, Y Komatsu, R Haraguchi, S Nakamura, K Suzuki, K Kosai, R Maas, G Yamada
    CELLULAR AND MOLECULAR BIOLOGY 45 5 589 - 599 1999年07月 [有り][無し]
     研究論文(学術雑誌) 
    A number of developmental regulatory genes, including homeobox genes, are dynamically expressed in the mammalian cephalic ectomesenchyme during craniofacial morphogenesis, Owing to the vast amount of gene knock out experiments, functions of such genes are now being revealed in the mammalian skeletal patterning process. The murine goosecoid (Gsc) and Msxl genes are expressed during craniofacial development and each mutant mouse displays intriguing facial abnormalities including those of middle ear ossicles, suggesting that both genes play roles in spatial programming of craniofacial regions. In order to examine whether these genes could function in concert to direct particular craniofacial morphogenesis, double knock out mice were analyzed. The phenotype of the double mutant mice was restricted to the first arch derivatives and was apparently additive of the single gene mutant mice, implying region specific genetic interactions of these homeobox genes expressed in overlapping regions of middle ear forming ectomesenchyme. Our results also suggested that the patterning of distal portions of the malleus depends on the tympanic membrane, for which normal expressions of both the genes are prerequisite.
  • Dysregulation of trace element composition in ovariectomized cynomolgus monkey bones
    G Yamada, S Nakamura, K Fukuzaki, H Izumi, N Horai, R Nagata, T Minami, Y Tohno, K Suzuki, R Haraguchi, K Miyado, T Toyoda, JC Izpisua-Belmonte, Maruyama, I, Kitajima, I
    CELLULAR AND MOLECULAR BIOLOGY 44 8 1205 - 1213 1998年12月 [有り][無し]
     
    One of the challenging issues in modern biomedical science is the increasing number of osteoporosis patients due to the expansion of elderly populations. Among aging-related pathogenic changes, alterations in bone function and skeletal pathogenesis is a particularly important issue of concern. Osteoporosis is one of the most serious bone-related pathogenic states, as it causes serious loss of quality of Life. Alterations in estrogen levels in accordance with aging are one of the key risk factors for osteoporosis. Complexed estrogen actions on bones can be traced by analyzing bone mineral components, as those elements accumulate as mineral complexes, reflecting the context of multiple cellular reactions such as bone resorption/osteogenesis. We have analyzed bone trace element composition in ovariectomized (OVX-treated) Cynomolgus monkey models in this study. In order to gain insights into the effects of such defects on bone trace element composition, inductively coupled plasma atomic emissions spectrometry (ICP-AES) analysis was performed. Marked changes in bone trace element levels were found in vertebral bones of OVX-treated Cynomolgus monkeys. An assessment of these trace element spectra in OVX model animals is discussed. These results could provide useful markers for understanding the physiological states of bones in postmenopausal women.
  • G Yamada, S Nakamura, R Haraguchi, K Terai, S Nomura, Y Kitamura, T Minami, MO Yamada, S Suzuki, H Izumi, R Nagata
    BIOLOGICAL TRACE ELEMENT RESEARCH 62 1-2 75 - 82 1998年04月 [有り][無し]
     研究論文(学術雑誌) 
    It has been recognized that bone trace element composition analysis provides clues when analyzing bone-related physiological conditions. Increasing numbers of bone-related genetic diseases have been identified recently. Ln this study, we have analyzed bone trace element composition in a genetic mutant animal model. Mutations in the mouse microphthalmia (mi) gene affect the development of a number of cell types, including melanocytes, mast cells, and osteoclasts. Previous studies have shown that different alleles of the mi locus show osteopetrosis. In order to gain insights into the effects of a particular genetic defect on bone trace element composition and bone structure, we performed bone trace element composition analysis using inductively coupled plasma atomic emissions spectrometry (ICP-AES). Marked changes in bone trace element levels were found in vertebrate bones of mi mutant mice. The implications and possible applications of bone trace element analysis will be discussed in this article.
  • Aberrant regulation of bone trace elements in motheaten and osteopetrosis mutant mice
    G Yamada, S Nakamura, R Haraguchi, M Sakai, K Suzuki, K Miyado, H Hasuwa, Y Ogino, T Minami, Y Tohno, M Blum, LD Shultz
    CELLULAR AND MOLECULAR BIOLOGY 44 2 315 - 319 1998年03月 [有り][無し]
     研究論文(学術雑誌) 
    Increasing numbers of genetic diseases involving bone development and models for these diseases have been identified recently. Analysis of these bone diseases have revealed that regulated action of multiple growth factors and subsequent signal transduction are essential for normal bone formation. In this paper, two murine mutant mice viable motheaten and osteopetrosis are analyzed. Mice with the recessive 'viable motheaten' mutation express a severe immunodeficiency syndrome and bone defects. Mutations at the motheaten locus were shown to be the result of aberrant splicing of the gene encoding hematopoietic cell phosphatase (Hcph). Mice homozygous for the osteopetrosis mutation develop congenital osteopetrosis due to a severe deficiency of osteoclasts. It has been recognized that bone trace element composition analysis helps to define bone-related physiological conditions. We have analyzed bone trace element composition in viable motheaten and osteopetrosis mutant animal models in this study. In order to gain insights into the effects of particular genetic defects on bone trace element composition, inductively coupled plasma atomic emissions spectrometry (ICP-AES) analysis was performed. Marked changes in bone trace element levels were found in limb bones of viable motheaten and osteopetrosis mutant mice. An assessment of these trace element spectrum in the two mutant models with respect to each genetic defects are discussed in this paper.
  • An efficient liposome-mediated gene transfer into the branchial arch, neural tube and the heart of chick embryos; A strategy to elucidate the organo genesis
    G Yamada, S Nakamura, R Haraguchi, M Sakai, T Terashi, S Sakisaka, T Toyoda, Y Ogino, H Hatanaka, Y Kaneda
    CELLULAR AND MOLECULAR BIOLOGY 43 8 1165 - 1169 1997年12月 [有り][無し]
     
    Hemagglutinating virus of Japan (HVJ)-liposome mediated gene-transfer permitted to clarify the mechanisms of embryonic organogenesis of the branchial arches, neural tubes and heart by micro-injecting reporter-plasmid DNA, containing the Escherichia coli LacZ gene, in embryos at several stages.

書籍

  • 組織細胞化学 2019 エピジェネティクスと組織化学
    北澤荘平, 原口竜摩, 鷹岡友紀, 北澤理子 ()
    日本組織細胞化学会 2019年

講演・口頭発表等

  • ストレプトゾトシン誘導性糖尿病腎における腎尿細管に注目した病理形態学的考察  [通常講演]
    原口竜摩, 松林加那子, 小原幸弘, 北澤理子, 北澤荘平
    第60回 日本組織細胞化学会・学術集会 2019年09月 ポスター発表 兵庫県神戸市
  • 近位尿細管に注目したストレプトゾトシン誘導性糖尿病腎の病態組織学的考察  [通常講演]
    原口竜摩, 松林加那子, 北澤理子, 北澤荘平
    第108回 日本病理学会・学術集会 2019年05月 ポスター発表 東京都
  • ヘッジホッグシグナルを介する成長板を発生起点とした骨格形成の理解  [通常講演]
    原口竜摩
    骨代謝学会Skeletal Science Retreat 2018 2018年11月 口頭発表(一般) 神奈川県三浦市
  • ヘッジホッグシグナルを介する成長板を発生起点とした骨格形成の理解  [招待講演]
    原口竜摩, 北澤理子, 北澤荘平
    第59回 日本組織細胞化学会・学術集会 2018年09月 シンポジウム・ワークショップパネル(指名) 宮崎県宮崎市
  • Developmental contribution of growth plate-derived hedgehog signal-responsive cells in growing bone.  [通常講演]
    Haraguchi R, Kitazawa R, Imai Y, Kitazawa S
    ASBMR 2018 Annual Meeting 2018年09月 ポスター発表 カナダ モントリオール市
  • 成長板を発生起点とするヘッジホッグシグナル受容細胞の骨格形成への関与  [通常講演]
    原口竜摩, 北澤理子, 今井祐記, 北澤荘平
    第36回 日本骨代謝学会・学術集会 2018年07月 ポスター発表 長崎県長崎市
  • 成長板に由来するヘッジホッグシグナル受容細胞の骨格発生における役  [通常講演]
    原口竜摩, 北澤理子, 北澤荘平
    第107回 日本病理学会・学術集会 2018年06月 ポスター発表 北海道札幌市
  • 新たな女性生殖器の発生機序:ウォルフ管に依存する子宮の発生  [招待講演]
    原口竜摩, 北澤理子, 村嶋亜紀, 山田 源, 北澤荘平
    第58回 日本組織細胞化学会・学術集会 2017年09月 シンポジウム・ワークショップパネル(指名) 愛媛県東温市
  • 長管骨伸長時におけるヘッジホッグシグナル受容細胞の組織系譜解析  [通常講演]
    原口竜摩, 北澤理子, 今井祐記, 北澤荘平
    第35回 日本骨代謝学会・学術集会 2017年07月 口頭発表(一般) 福岡県博多市
  • 体腔上皮に由来するWnt/β-カテニンシグナルの子宮発生における役割  [通常講演]
    原口竜摩, 北澤理子, 北澤荘平
    第106回 日本病理学会・学術集会 2017年05月 ポスター発表 東京都
  • 破骨細胞におけるヘッジホッグシグナル伝達系の機能解析  [通常講演]
    原口竜摩, 北澤理子, 今井祐記, 北澤荘平
    第57回 日本組織細胞化学会・学術集会 2016年09月 ポスター発表 東京都
  • The functional role of Hedgehog signaling in osteoclast lineage.  [通常講演]
    Haraguchi R, Kitazawa R, Imai Y, Kitazawa S
    ASBMR 2016 Annual Meeting 2016年09月 ポスター発表 米国 アトランタ市
  • 破骨細胞系列におけるヘッジホッグシグナル伝達系の機能解析  [通常講演]
    原口竜摩, 北澤理子, 今井祐記, 北澤荘平
    第34回 日本骨代謝学会・学術集会 2016年07月 ポスター発表 大阪市
  • 破骨細胞系列におけるヘッジホッグシグナル伝達系の機能解析  [通常講演]
    原口竜摩, 北澤理子, 小林泰浩, 今井祐記, 北澤荘平
    第105回 日本病理学会・学術集会 2016年05月 ポスター発表 宮城県仙台市
  • ヘッジホッグシグナルを介する成長板を起点とした長管骨発生プロセスの理解  [招待講演]
    原口竜摩, 北澤理子, 北澤荘平
    第56回 日本組織細胞化学会・学術集会 2015年10月 シンポジウム・ワークショップパネル(指名) 大阪府枚方市
  • The role of Wnt signal modulator, sFRP4, in bone formation and metabolism.  [通常講演]
    Haraguchi R, Kitazawa R, Imai Y, Kitazawa S
    ASBMR 2015 Annual Meeting 2015年10月 ポスター発表 米国 シアトル市
  • Wntシグナル調節因子sFRP-4を指標とした骨代謝研究:骨代謝疾患との関連性について  [招待講演]
    原口竜摩, 北澤理子, 北澤荘平
    第47回 日本臨床分子形態学会・学術集会 2015年09月 シンポジウム・ワークショップパネル(指名) 長崎県長崎市
  • Wntシグナル調節因子sFRP-4の骨形成・骨代謝プロセスにおける役割  [通常講演]
    原口竜摩, 北澤理子, 今井祐記, 北澤荘平
    第34回 日本骨代謝学会・学術集会 2015年07月 ポスター発表 東京都
  • 長管骨伸長プロセスにおけるヘッジホッグシグナル経路の役割  [通常講演]
    原口竜摩, 北澤理子, 北澤荘平
    第104回 日本病理学会・学術集会 2015年04月 口頭発表(一般) 愛知県名古屋市
  • 長管骨伸長プロセスにおけるヘッジホッグシグナルの機能考察  [招待講演]
    原口竜摩, 北澤理子, 北澤荘平
    第46回 日本臨床分子形態学会・学術集会 2014年10月 シンポジウム・ワークショップパネル(指名) 東京都
  • 第二次性徴期の長管骨伸長プロセスにおけるヘッジホッグシグナル経路の役割について  [通常講演]
    原口竜摩, 北澤理子, 北澤荘平
    第33回 日本骨代謝学会・学術集会 2014年07月 ポスター発表 大阪市
  • 組織系譜解析から紐解くWnt/β-カテニンシグナルを中心とした子宮発生メカニズム  [通常講演]
    原口竜摩, 北澤理子, 平田 務, 北澤荘平
    第103回 日本病理学会・学術集会 2014年04月 ポスター発表 広島県広島市
  • 組織系譜解析から紐解くWnt/β-カテニンシグナルを中心とした子宮発生メカニズム  [通常講演]
    原口竜摩, 北澤理子, 平田 務, 北澤荘平
    第119回 日本解剖学会・学術集会 2014年03月 ポスター発表 栃木県下野市
  • Spatio-temporal expression of Tbx18 during endochondral bone formation.  [通常講演]
    Haraguchi R, Kitazawa R, Kitazawa S
    The 14th International Congress of Histochemistry and Cytochemistry 2012年08月 ポスター発表 日本 京都市
  • Unique functions of Sonic hedgehog signaling during external genitalia development.  [通常講演]
    Haraguchi R, Hui CC, Motoyama J, Makino S, Shiroishi T, Gaffield W, Yamada G
    EMBL Mouse Molecular Genetics meeting 2001年08月 ポスター発表 独 ハイデルベルグ市
  • Unique functions of Sonic hedgehog signaling during external genitalia development.  [通常講演]
    Haraguchi R, Gaffield W, Motoyama J, Shiroishi T, Hui CC, Yamada G
    The 34th International Congress of Developmental Biology 2001年07月 ポスター発表 日本 京都市

MISC

  • 小原幸弘, 原口竜摩, 北澤理子, 北澤理子, 北澤荘平 日本組織細胞化学会総会・学術集会講演プログラム・予稿集 60th 99 2019年09月 [無し][無し]
  • 原口竜摩, 小原幸弘, 松林加那子, 北澤理子, 北澤理子, 北澤荘平 日本組織細胞化学会総会・学術集会講演プログラム・予稿集 60th 95 2019年09月 [無し][無し]
  • ヘッジホッグシグナル調節因子Hhipの骨形成過程における役割
    原口 竜摩, 小原 幸弘, 今井 祐記, 北澤 理子, 北澤 荘平 日本骨代謝学会学術集会プログラム抄録集 37回 221 -221 2019年09月 [無し][無し]
  • 破骨細胞分化因子受容体RANKのプロモータ領域メチル化による発現制御
    北澤 理子, 村田 夕紀, 小原 幸弘, 原口 竜摩, 北澤 荘平 日本骨代謝学会学術集会プログラム抄録集 37回 226 -226 2019年09月 [無し][無し]
  • ヘッジホッグシグナル阻害剤であるCyclopamineは破骨細胞形成を抑制する
    小原 幸弘, 原口 竜摩, 北澤 理子, 北澤 荘平 日本骨代謝学会学術集会プログラム抄録集 37回 227 -227 2019年09月 [無し][無し]
  • 組織化学イメージングで探る硬組織の細胞機能 ヘッジホッグシグナルを介する成長板を発生起点とした骨格形成の理解
    原口 竜摩, 北澤 理子, 北澤 荘平 日本組織細胞化学会総会・学術集会講演プログラム・予稿集 59回 44 -44 2018年09月 [無し][無し]
  • 組織in situでのメチル化シトシン検出手法の開発
    矢野 可蓮, 原口 竜摩, 城戸 貴弘, 神崎 摩耶, 北澤 理子, 北澤 荘平 日本組織細胞化学会総会・学術集会講演プログラム・予稿集 59回 58 -58 2018年09月 [無し][無し]
  • 成長板を発生起点とするヘッジホッグシグナル受容細胞の骨格形成への関与
    原口 竜摩, 北澤 理子, 今井 祐記, 北澤 荘平 日本骨代謝学会学術集会プログラム抄録集 36回 163 -163 2018年07月 [無し][無し]
  • 破骨細胞分化因子受容体RANKのプロモータ領域メチル化による発現制御
    北澤 理子, 村田 夕紀, 原口 竜摩, 上田 康雄, 福島 万奈, 北澤 荘平 日本骨代謝学会学術集会プログラム抄録集 36回 183 -183 2018年07月 [無し][無し]
  • 破骨細胞分化因子受容体RANKの新規変異体vRANKの機能解析(Functional analysis of a novel splicing variant of receptor activator of NF-κB)
    北澤 理子, 原口 竜摩, 上田 康雄, 福島 万奈, 北澤 荘平 日本病理学会会誌 107 (1) 343 -343 2018年04月 [無し][無し]
  • Calmodulin-like 5(CALML5)の子宮頸部扁平上皮癌における発現制御
    上田 康雄, 北澤 理子, 福島 万奈, 近藤 武史, 原口 竜摩, 北澤 荘平 日本病理学会会誌 107 (1) 388 -388 2018年04月 [無し][無し]
  • 成長板に由来するヘッジホッグシグナル受容細胞の骨格発生における役割
    原口 竜摩, 北澤 理子, 北澤 荘平 日本病理学会会誌 107 (1) 494 -494 2018年04月 [無し][無し]
  • 糖尿病により誘発される精子形成能低下とヘッジホッグシグナル経路との関連性について
    大野 輝之, 原口 竜摩, 齋藤 洋太, 下山 貴幸, 北澤 理子, 北澤 荘平 日本病理学会会誌 107 (1) 515 -515 2018年04月 [無し][無し]
  • 中枢神経系におけるヘッジホッグシグナル依存的な糖尿病合併症
    池田 真子, 原口 竜摩, 北澤 理子, 北澤 荘平 日本病理学会会誌 107 (1) 516 -516 2018年04月 [無し][無し]
  • 下部消化管糖尿病合併症におけるヘッジホッグシグナル経路の関与
    倉田 菜央, 原口 竜摩, 小野田 杏奈, 北澤 理子, 北澤 荘平 日本病理学会会誌 107 (1) 517 -517 2018年04月 [無し][無し]
  • 糖尿病性骨減少に抵抗性を示すsFRP-4遺伝子欠損マウスの病態組織学的考察
    伊吹 優里, 原口 竜摩, 北澤 理子, 今井 祐記, 北澤 荘平 日本病理学会会誌 107 (1) 520 -520 2018年04月 [無し][無し]
  • 生殖器の発生・疾患研究の最前線 新たな女性生殖器の発生機序 ウォルフ管に依存する子宮の発生
    原口 竜摩, 北澤 理子, 村嶋 亜紀, 山田 源, 北澤 荘平 日本組織細胞化学会総会・学術集会講演プログラム・予稿集 58回 37 -37 2017年09月 [無し][無し]
  • 破骨細胞分化因子受容体RANKの新規変異体vRANKの解析
    北澤 理子, 原口 竜摩, 水野 洋輔, 北澤 荘平 日本病理学会会誌 106 (1) 307 -307 2017年03月 [無し][無し]
  • 網羅的遺伝子解析による滑膜肉腫の検討
    水野 洋輔, 北澤 理子, 原口 竜摩, 北澤 荘平 日本病理学会会誌 106 (1) 413 -413 2017年03月 [無し][無し]
  • 体腔上皮に由来するWnt/β-カテニンシグナルの子宮発生における役割
    原口 竜摩, 北澤 理子, 北澤 荘平 日本病理学会会誌 106 (1) 454 -454 2017年03月 [無し][無し]
  • 髄膜腫における砂粒体形成とカルシウム感知受容体CaSR発現との関連について
    石村 菜穂, 北澤 理子, 原口 竜摩, 北澤 荘平 日本病理学会会誌 106 (1) 508 -508 2017年03月 [無し][無し]
  • 上部消化管におけるヘッジホッグシグナル依存的な糖尿病合併症
    玉井 優衣, 原口 竜摩, 北澤 理子, 北澤 荘平 日本病理学会会誌 106 (1) 512 -513 2017年03月 [無し][無し]
  • 膵組織の恒常性および酸化的ストレス下での小腸組織におけるヘッジホッグシグナルの役割
    小野田 杏奈, 北澤 荘平, 原口 竜摩, 北澤 理子, 玉井 優衣, 倉田 菜央 日本病理学会会誌 106 (1) 514 -514 2017年03月 [無し][無し]
  • マウス前破骨細胞株RAW細胞における受容体RANK遺伝子発現調節領域のメチル化と破骨細胞分化能の解析
    村田 夕紀, 北澤 荘平, 原口 竜摩, 北澤 理子 日本病理学会会誌 106 (1) 518 -518 2017年03月 [無し][無し]
  • Nanta母斑(osteo-nevus of Nanta)について、異所性骨形成メカニズムの解析
    下山 貴幸, 北澤 荘平, 原口 竜摩, 北澤 理子 日本病理学会会誌 106 (1) 521 -521 2017年03月 [無し][無し]
  • sFRP-4遺伝子ノックアウトマウスは、糖尿病性骨減少に抵抗性を示す
    伊吹 優里, 原口 竜摩, 北澤 理子, 北澤 荘平, 今井 祐記 日本病理学会会誌 106 (1) 522 -522 2017年03月 [無し][無し]
  • 長管骨におけるヘッジホッグシグナル依存的な糖尿病合併症
    工藤 聡, 原口 竜摩, 永山 正和, 北澤 理子, 北澤 荘平 日本病理学会会誌 106 (1) 522 -522 2017年03月 [無し][無し]
  • 骨巨細胞腫ホルマリン固定パラフィン包埋検体を抗原とするモノクローナル抗体1G7の樹立と認識抗原の解析
    木内 理奈, 北澤 理子, 森 礼子, 水野 洋輔, 原口 竜摩, 北澤 荘平 日本病理学会会誌 106 (1) 522 -522 2017年03月 [無し][無し]
  • 骨巨細胞腫ホルマリン固定パラフィン包埋検体を抗原とするモノクローナル抗体2H1の樹立と認識抗原の解析
    森 礼子, 北澤 理子, 木内 理奈, 水野 洋輔, 原口 竜摩, 北澤 荘平 日本病理学会会誌 106 (1) 523 -523 2017年03月 [無し][無し]
  • 腎臓におけるヘッジホッグシグナル依存的な糖尿病合併症
    島瀬 奈津子, 原口 竜摩, 北澤 理子, 北澤 荘平 日本病理学会会誌 106 (1) 525 -525 2017年03月 [無し][無し]
  • 中枢神経系におけるヘッジホッグシグナル依存的な糖尿病合併症
    池田 真子, 原口 竜摩, 山下 百合菜, 本間 理沙子, 北澤 理子, 北澤 荘平 日本病理学会会誌 106 (1) 526 -526 2017年03月 [無し][無し]
  • 糖尿病による精子形成能低下とヘッジホッグシグナル経路の関連性について
    大野 輝之, 原口 竜摩, 齋藤 洋太, 下山 貴幸, 北澤 理子, 北澤 荘平 日本病理学会会誌 106 (1) 526 -526 2017年03月 [無し][無し]
  • 中枢神経系におけるヘッジホッグシグナル依存的な糖尿病合併症 遺伝子改変マウスモデルを用いた細胞系譜追跡システムによる分子病理学的研究
    池田 真子, 原口 竜摩, 山下 百合菜, 本間 理沙子, 北澤 理子, 北澤 荘平 日本組織細胞化学会総会・学術集会講演プログラム・予稿集 57回 60 -60 2016年09月 [無し][無し]
  • 上部消化管におけるヘッジホッグシグナル依存的な糖尿病合併症 遺伝子改変マウスモデルを用いた細胞系譜追跡システムによる分子病理的研究
    玉井 優衣, 原口 竜摩, 西村 智達, 北澤 理子, 北澤 荘平 日本組織細胞化学会総会・学術集会講演プログラム・予稿集 57回 62 -62 2016年09月 [無し][無し]
  • 長管骨におけるヘッジホッグシグナル依存的な糖尿病合併症 遺伝子改変マウスモデルを用いた細胞系譜追跡システムによる分子病理学的研究
    永山 正和, 原口 竜摩, 工藤 聡, 北澤 理子, 北澤 荘平 日本組織細胞化学会総会・学術集会講演プログラム・予稿集 57回 68 -68 2016年09月 [無し][無し]
  • 破骨細胞におけるヘッジホッグシグナル伝達系の機能解析
    原口 竜摩, 北澤 理子, 今井 祐記, 北澤 荘平 日本組織細胞化学会総会・学術集会講演プログラム・予稿集 57回 69 -69 2016年09月 [無し][無し]
  • 破骨細胞分化因子受容体RANKの新規変異体vRANKの機能解析
    北澤 理子, 原口 竜摩, 水野 洋輔, 上田 康雄, 小林 泰浩, 北澤 荘平 日本骨代謝学会学術集会プログラム抄録集 34回 174 -174 2016年07月 [無し][無し]
  • 破骨細胞系列におけるヘッジホッグシグナル伝達系の機能解析
    原口 竜摩, 北澤 理子, 今井 祐記, 北澤 荘平 日本骨代謝学会学術集会プログラム抄録集 34回 210 -210 2016年07月 [無し][無し]
  • 破骨細胞分化因子受容体RANKの新規変異体vRANKの解析(Identification and analysis of function of a novel splicing variant of receptor activation of NF-κB)
    北澤 理子, 原口 竜摩, 水野 洋輔, 北澤 荘平 日本病理学会会誌 105 (1) 326 -326 2016年04月 [無し][無し]
  • 単相型と二相型の滑膜肉腫における遺伝子発現の違い
    水野 洋輔, 北澤 理子, 原口 竜摩, 北澤 荘平 日本病理学会会誌 105 (1) 540 -540 2016年04月 [無し][無し]
  • 破骨細胞系列におけるヘッジホッグシグナル伝達系の機能解析
    原口 竜摩, 北澤 理子, 小林 泰浩, 今井 祐記, 北澤 荘平 日本病理学会会誌 105 (1) 543 -543 2016年04月 [無し][無し]
  • 新規のGLI3遺伝子変異が証明されたGreig尖頭多合指症候群の一剖検症例
    伊藤 才季, 北澤 理子, 原口 竜摩, 北澤 荘平 日本病理学会会誌 105 (1) 582 -582 2016年04月 [無し][無し]
  • アガロースビーズ法で10年以上前の肺生検HE染色標本からEML4-ALKキメラ遺伝子の存在とその亜型を同定できる
    廣瀬 未優, 北澤 理子, 原口 竜摩, 北澤 荘平 日本病理学会会誌 105 (1) 587 -587 2016年04月 [無し][無し]
  • Padlock probeを用いたH-RCA法による病理組織切片上でのDNA1塩基突然変異の検出法の開発
    沖田 将慶, 北澤 理子, 原口 竜摩, 北澤 荘平 日本病理学会会誌 105 (1) 589 -589 2016年04月 [無し][無し]
  • 下部消化管糖尿病合併症におけるヘッジホッグシグナル経路の関与
    倉田 菜央, 原口 竜摩, 伊吹 優里, 玉井 優衣, 西村 智達, 北澤 理子, 北澤 荘平 日本病理学会会誌 105 (1) 595 -595 2016年04月 [無し][無し]
  • 腎臓におけるヘッジホッグシグナル依存的な糖尿病合併症
    島瀬 奈津子, 原口 竜摩, 池田 真子, 小野田 杏奈, 北澤 理子, 北澤 荘平 日本病理学会会誌 105 (1) 595 -595 2016年04月 [無し][無し]
  • 骨巨細胞腫ホルマリン固定パラフィン包埋検体を抗原とするモノクローナル抗体1G7の樹立と認識抗原の解析
    木内 理奈, 北澤 理子, 森 礼子, 水野 洋輔, 原口 竜摩, 北澤 荘平 日本病理学会会誌 105 (1) 596 -596 2016年04月 [無し][無し]
  • ヒト白血病細胞株HL60の破骨細胞への分化誘導の検討
    田中 いつみ, 北澤 荘平, 原口 竜摩, 北澤 理子 日本病理学会会誌 105 (1) 596 -596 2016年04月 [無し][無し]
  • 髄膜腫における砂粒体形成とカルシウム感知受容体CaSR発現との関連について
    石村 菜穂, 北澤 理子, 水野 洋輔, 原口 竜摩, 北澤 荘平 日本病理学会会誌 105 (1) 597 -597 2016年04月 [無し][無し]
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    村田 夕紀, 北澤 荘平, 原口 竜摩, 北澤 理子 日本病理学会会誌 105 (1) 597 -597 2016年04月 [無し][無し]
  • 骨巨細胞腫ホルマリン固定パラフィン包埋検体を抗原とするモノクローナル抗体2H1の樹立と認識抗原の解析
    森 礼子, 北澤 理子, 木内 理奈, 水野 洋輔, 原口 竜摩, 北澤 荘平 日本病理学会会誌 105 (1) 597 -597 2016年04月 [無し][無し]
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    菊澤 里佳子, 北澤 理子, 原口 竜摩, 北澤 荘平 日本病理学会会誌 105 (1) 598 -598 2016年04月 [無し][無し]
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    大野 輝之, 原口 竜摩, 齋藤 洋太, 下山 貴幸, 北澤 理子, 北澤 荘平 日本病理学会会誌 105 (1) 604 -604 2016年04月 [無し][無し]
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    原口 竜摩, 北澤 理子, 北澤 荘平 日本組織細胞化学会総会・学術集会講演プログラム・予稿集 56回 41 -41 2015年10月 [無し][無し]
  • 破骨細胞分化因子受容体RANKの新規変異体vRANKの解析
    北澤 理子, 原口 竜摩, 水野 洋輔, 小林 泰浩, 北澤 荘平 日本骨代謝学会学術集会プログラム抄録集 33回 158 -158 2015年07月 [無し][無し]
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    原口 竜摩, 北澤 理子, 今井 祐記, 北澤 荘平 日本骨代謝学会学術集会プログラム抄録集 33回 189 -189 2015年07月 [無し][無し]
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    原口 竜摩, 北澤 理子, 北澤 荘平 日本病理学会会誌 104 (1) 285 -285 2015年03月 [無し][無し]
  • 破骨細胞分化因子受容体RANKの新規変異体vRANKの解析
    北澤 理子, 原口 竜摩, 水野 洋輔, 北澤 荘平 日本病理学会会誌 104 (1) 285 -285 2015年03月 [無し][無し]
  • 単相型と二相型の滑膜肉腫における遺伝子発現の違い
    水野 洋輔, 北澤 理子, 原口 竜摩, 北澤 荘平 日本病理学会会誌 104 (1) 389 -389 2015年03月 [無し][無し]
  • 糖尿病による骨減少における分泌型WNT阻害蛋白質sFRP-4の役割
    本山 友美, 北澤 理子, 原口 竜摩, 北澤 荘平 日本病理学会会誌 104 (1) 390 -390 2015年03月 [無し][無し]
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    濱松 勇輝, 原口 竜摩, 北澤 理子, 北澤 荘平 日本病理学会会誌 104 (1) 508 -508 2015年03月 [無し][無し]
  • 拡張型心筋症は、高血糖による酸化的ストレスとペントシジンの非生理的コラーゲン架橋により進行が加速する
    菊澤 里佳子, 北澤 理子, 原口 竜摩, 北澤 荘平 日本病理学会会誌 104 (1) 509 -509 2015年03月 [無し][無し]
  • アガロースビーズ法で10年以上前の肺生検HE染色標本からEML4-ALKキメラ遺伝子の存在とその亜型を同定できる
    廣瀬 未優, 北澤 荘平, 原口 竜摩, 北澤 理子 日本病理学会会誌 104 (1) 511 -511 2015年03月 [無し][無し]
  • GLI3変異が証明された先天性胆嚢無形成、鎖肛、腸回転異常等の内臓多発奇形を伴ったGreig尖頭多合指症候群
    伊藤 才季, 北澤 理子, 原口 竜摩, 北澤 荘平 日本病理学会会誌 104 (1) 516 -516 2015年03月 [無し][無し]
  • H-RCA法およびPadlock probeを用いた組織切片上でのp16遺伝子メチル化検出
    二宮 鴻介, 北澤 荘平, 原口 竜摩, 北澤 理子 日本病理学会会誌 104 (1) 520 -520 2015年03月 [無し][無し]
  • 髄膜腫における砂粒体形成とカルシウム感知受容体CaSR発現との関連について
    石村 菜穂, 北澤 理子, 原口 竜摩, 北澤 荘平 日本病理学会会誌 104 (1) 525 -525 2015年03月 [無し][無し]
  • 星状膠腫へのbevacizumab治療効果に関する組織学的検討
    三田村 祐里, 北澤 理子, 原口 竜摩, 北澤 荘平 日本病理学会会誌 104 (1) 525 -525 2015年03月 [無し][無し]
  • 骨巨細胞腫ホルマリン固定パラフィン包埋検体を抗原とするモノクローナル抗体1G7の樹立と認識抗原の解析
    木内 理奈, 北澤 理子, 森 礼子, 水野 洋輔, 原口 竜摩, 北澤 荘平 日本病理学会会誌 104 (1) 526 -526 2015年03月 [無し][無し]
  • 骨巨細胞腫ホルマリン固定パラフィン包埋検体を抗原とするモノクローナル抗体2H1の樹立と認識抗原の解析
    森 礼子, 北澤 理子, 木内 理奈, 水野 洋輔, 原口 竜摩, 北澤 荘平 日本病理学会会誌 104 (1) 526 -526 2015年03月 [無し][無し]
  • マウス前破骨細胞株RAW264細胞における受容体RANK遺伝子発現調節領域のメチル化と破骨細胞分化能の解析
    村田 夕紀, 北澤 荘平, 原口 竜摩, 北澤 理子 日本病理学会会誌 104 (1) 527 -527 2015年03月 [無し][無し]
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    沖田 将慶, 北澤 理子, 原口 竜摩, 北澤 荘平 日本病理学会会誌 104 (1) 529 -529 2015年03月 [無し][無し]
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    田中 いつみ, 北澤 荘平, 原口 竜摩, 北澤 理子 日本病理学会会誌 104 (1) 530 -530 2015年03月 [無し][無し]
  • 悪性リンパ腫検体におけるMYD88遺伝子変異のin situ検出法の開発
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    原口 竜摩, 北澤 理子, 北澤 荘平 日本組織細胞化学会総会・学術集会講演プログラム・予稿集 55回 100 -100 2014年09月 [無し][無し]
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    木内 理奈, 北澤 理子, 森 礼子, 水野 洋輔, 原口 竜摩, 北澤 荘平 日本病理学会会誌 103 (2) 39 -39 2014年09月 [無し][無し]
  • 骨巨細胞腫ホルマリン固定パラフィン包埋検体を抗原とするモノクローナル抗体2H1の樹立と認識抗原の性状解析(第一報)
    森 礼子, 北澤 理子, 木内 理奈, 水野 洋輔, 原口 竜摩, 北澤 荘平 日本病理学会会誌 103 (2) 40 -40 2014年09月 [無し][無し]
  • 星状膠腫へのbevacizumab治療効果に関する組織学的検討
    三田村 祐里, 北澤 理子, 水野 洋輔, 原口 竜摩, 北澤 荘平 日本病理学会会誌 103 (2) 64 -64 2014年09月 [無し][無し]
  • 破骨細胞分化因子受容体RANKの新規変異体vRANKの解析
    北澤 理子, 原口 竜摩, 向井 智美, 永井 由紗, 北澤 荘平 日本骨代謝学会学術集会プログラム抄録集 32回 205 -205 2014年07月 [無し][無し]
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  • 破骨細胞分化因子受容体RANKの新規変異体vRANKの解析
    北澤 理子, 向井 智美, 永井 由紗, 原口 竜摩, 北澤 荘平 日本病理学会会誌 103 (1) 271 -271 2014年03月 [無し][無し]
  • 単相型と二相型の滑膜肉腫における発現遺伝子の違い
    水野 洋輔, 北澤 理子, 杉田 敦郎, 久野 美子, 原口 竜摩, 北澤 荘平 日本病理学会会誌 103 (1) 361 -361 2014年03月 [無し][無し]
  • 組織系譜解析から紐解くWnt/β-カテニンシグナルを中心とした子宮発生メカニズム
    原口 竜摩, 北澤 理子, 平田 務, 北澤 荘平 日本病理学会会誌 103 (1) 373 -373 2014年03月 [無し][無し]
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    桑原 奈都美, 北澤 理子, 原口 竜摩, 北澤 荘平 日本病理学会会誌 103 (1) 390 -390 2014年03月 [無し][無し]
  • 胃癌におけるCDX2遺伝子のメチル化メモリー現象とMeCP2の発現について
    亀岡 祐里, 北澤 理子, 原口 竜摩, 北澤 荘平 日本病理学会会誌 103 (1) 390 -390 2014年03月 [無し][無し]
  • 非定型的エピジェネティクス調節機構によるマウスKCNE2遺伝子発現制御についての検討
    濱松 勇輝, 北澤 理子, 木内 理奈, 原口 竜摩, 北澤 荘平 日本病理学会会誌 103 (1) 391 -391 2014年03月 [無し][無し]
  • 十二指腸異所性胃粘膜には高頻度でβ-カテニンの遺伝子変異が存在する
    中川 みく, 北澤 理子, 二宮 鴻介, 沖田 将慶, 原口 竜摩, 北澤 荘平 日本病理学会会誌 103 (1) 392 -392 2014年03月 [無し][無し]
  • ヒト副甲状腺二次性過形成組織におけるPadlock probeを用いた組織切片上でのメチル化検出
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  • Padlock probeとhyperbranching rolling circle amplificationを用いた組織切片上でのDNA1塩基変異の検出
    沖田 将慶, 北澤 理子, 二宮 鴻介, 菊澤 里佳子, 伊藤 才季, 原口 竜摩, 北澤 荘平 日本病理学会会誌 103 (1) 399 -399 2014年03月 [無し][無し]
  • ヒト白血病細胞株HL60の破骨細胞への分化誘導の検討
    田中 いつみ, 北澤 理子, 森 礼子, 原口 竜摩, 北澤 荘平 日本病理学会会誌 103 (1) 399 -399 2014年03月 [無し][無し]
  • マウス前破骨細胞株RAW264における破骨細胞分化能と受容体RANK発現の解析
    村田 夕紀, 北澤 理子, 三田村 佑里, 原口 竜摩, 北澤 荘平 日本病理学会会誌 103 (1) 399 -399 2014年03月 [無し][無し]
  • 高血糖による酸化的ストレス、ペントシジン架橋により、治療抵抗性心不全を来した拡張型心筋症の一剖検例
    菊澤 里佳子, 北澤 理子, 伊藤 才季, 沖田 将慶, 二宮 鴻介, 久野 美子, 水野 洋輔, 杉田 篤郎, 原口 竜摩, 北澤 荘平 日本病理学会会誌 103 (1) 400 -400 2014年03月 [無し][無し]
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  • 耳下腺原発DLBCLの治療中に新たなMYD88遺伝子L265P変異を生じた一剖検例
    藤石 琴, 北澤 理子, 原口 竜摩, 北澤 荘平 日本病理学会会誌 103 (1) 406 -406 2014年03月 [無し][無し]
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    伊藤 千尋, 北澤 理子, 原口 竜摩, 北澤 荘平 日本病理学会会誌 103 (1) 407 -407 2014年03月 [無し][無し]
  • 先天性胆嚢無形成を伴う多発奇形児の考察
    伊藤 才季, 北澤 理子, 菊澤 里佳子, 二宮 鴻介, 沖田 将慶, 近藤 武史, 原口 竜摩, 北澤 荘平 日本病理学会会誌 103 (1) 408 -408 2014年03月 [無し][無し]
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    原口 竜摩, 北澤 理子, 平田 務, 北澤 荘平 日本生殖医学会雑誌 58 (4) 433 -433 2013年10月 [無し][無し]
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  • Padlock probeとhyperbranching rolling circle amplification(H-RCA)法を用いた病理組織切片上でのDNA1塩基突然変異の検出
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  • Genetic lineage Tracing法によるWnt/β-カテニンシグナルに着目した子宮発生機序についての考察
    原口 竜摩, 北澤 理子, 平田 務, 北澤 荘平 日本組織細胞化学会総会・学術集会講演プログラム・予稿集 54回 68 -68 2013年09月 [無し][無し]
  • 高血糖によるペントシジン架橋により、心不全の進行を来した拡張型心筋症の一剖検症例
    菊澤 里佳子, 北澤 理子, 伊藤 才季, 沖田 将慶, 二宮 鴻介, 曽我 美子, 水野 洋輔, 杉田 篤郎, 原口 竜摩, 北澤 荘平 日本病理学会会誌 102 (2) 38 -38 2013年09月 [無し][無し]
  • 胆嚢欠損を伴う多発奇形の一剖検例
    伊藤 才季, 北澤 理子, 菊澤 里佳子, 沖田 将慶, 二宮 鴻介, 原口 竜摩, 近藤 武史, 北澤 荘平 日本病理学会会誌 102 (2) 41 -41 2013年09月 [無し][無し]
  • 致死的小腸潰瘍をきたした末梢性T細胞性リンパ腫の1剖検例
    北澤 理子, 竹治 智, 黒田 太良, 川崎 敬太郎, 日浅 陽一, 池田 宜央, 薬師神 芳洋, 杉田 敦郎, 原口 竜摩, 北澤 荘平 日本病理学会会誌 102 (2) 43 -43 2013年09月 [無し][無し]
  • 破骨細胞分化因子受容体RANKの新規変異体の解析
    北澤 理子, 向井 智美, 永井 由紗, 近藤 武史, 原口 竜摩, 北澤 荘平 日本病理学会会誌 102 (1) 311 -311 2013年04月 [無し][無し]
  • レプトスピラ感染から血球貪食症候群を発症した1剖検例
    水野 洋輔, 曽我 美子, 杉田 敦朗, 金子 政彦, 原口 竜摩, 北澤 理子, 北澤 荘平 日本病理学会会誌 102 (1) 434 -434 2013年04月 [無し][無し]
  • 雄性生殖管-ウォルフ管-に着目した雌性生殖器の発生機序についての考察
    原口 竜摩, 北澤 理子, 松丸 大輔, 山田 源, 北澤 荘平 日本病理学会会誌 102 (1) 436 -436 2013年04月 [無し][無し]
  • 剖検にて診断された特発性肝類洞閉塞症候群の一例
    河南 幸乃, 西 祐貴子, 有安 奏, 原口 竜摩, 北澤 理子, 北澤 荘平 日本病理学会会誌 102 (1) 492 -492 2013年04月 [無し][無し]
  • 胃癌におけるCDX2遺伝子のメチル化メモリー現象とMUC2の発現について
    亀岡 祐里, 立花 亮祐, 有安 奏, 原口 竜摩, 北澤 理子, 北澤 荘平 日本病理学会会誌 102 (1) 492 -492 2013年04月 [無し][無し]
  • 胎児期骨形成過程におけるSfrp4遺伝子発現解析
    立花 亮祐, 原口 竜摩, 亀岡 祐里, 有安 奏, 森 清, 近藤 武史, 北澤 荘平, 北澤 理子 日本病理学会会誌 102 (1) 493 -493 2013年04月 [無し][無し]
  • 消化管Inflammatory fibroid polypにおけるPDGFRα遺伝子異常の解析
    有安 奏, 西 祐貴子, 河南 幸乃, 亀岡 祐里, 原口 竜摩, 北澤 理子, 北澤 荘平 日本病理学会会誌 102 (1) 495 -495 2013年04月 [無し][無し]
  • 十二指腸異所性胃粘膜におけるβカテニン遺伝子変異の検討
    中川 みく, 沖田 将吉, 菊澤 里佳子, 二宮 鴻介, 原口 竜摩, 北澤 理子, 北澤 荘平 日本病理学会会誌 102 (1) 497 -497 2013年04月 [無し][無し]
  • 糖尿病に合併した難治性肺高血圧症の1剖検例
    薦田 宗則, 北澤 理子, 牧田 憲二, 吉田 圭佑, 竹治 みゆき, 曽我 美子, 倉田 美恵, 原口 竜摩, 北澤 荘平 日本病理学会会誌 101 (2) 36 -36 2012年09月 [無し][無し]
  • 多系統萎縮症(Multiple-System Atrophy)の1剖検例
    永井 由紗, 北澤 理子, 中川 みく, 薦田 宗則, 近藤 武史, 原口 竜摩, 北澤 荘平 日本病理学会会誌 101 (2) 40 -40 2012年09月 [無し][無し]
  • バレット食道の「化生-異形成-癌」進行過程におけるCDX2発現とそのプロモータメチル化の関係(CDX2 expression and its promoter methylation during metaplasia-dysplasia-carcinoma sequence in Barrett esophagus)
    牧田 憲二, 北澤 理子, 仙波 秀峰, 中川 みく, 藤石 琴, 原口 竜摩, 北澤 荘平 日本癌学会総会記事 71回 380 -380 2012年08月 [無し][無し]
  • 破骨細胞分化因子RANKLによる受容体RANKの発現制御機構
    北澤 理子, 向井 智美, 石井 淳子, 近藤 武史, 森 清, 原口 竜摩, 北澤 荘平 日本骨代謝学会学術集会プログラム抄録集 30回 188 -188 2012年07月 [無し][無し]
  • 骨形成過程におけるTbx18遺伝子の役割
    原口 竜摩, 北澤 理子, 北澤 荘平 日本骨代謝学会学術集会プログラム抄録集 30回 254 -254 2012年07月 [無し][無し]
  • 破骨細胞分化因子RANKLによる受容体RANK発現制御
    北澤 理子, 向井 智美, 石井 淳子, 金藤 聡美, 近藤 武史, 森 清, 原口 竜摩, 北澤 荘平 日本病理学会会誌 101 (1) 269 -269 2012年03月 [無し][無し]
  • 胎児期骨形成過程におけるTbx18遺伝子の役割
    原口 竜摩, 北澤 理子, 北澤 荘平 日本病理学会会誌 101 (1) 343 -343 2012年03月 [無し][無し]
  • 9年の経過中にMYD88遺伝子の変異が生じた悪性リンパ腫の一症例
    藤石 琴, 永井 由紗, 渡部 貴文, 坂東 健次, 原口 竜摩, 北澤 理子, 北澤 荘平 日本病理学会会誌 101 (1) 439 -439 2012年03月 [無し][無し]
  • 前立腺原発のびまん性大細胞型B細胞リンパ腫non-germinal center B cell-like(non-GCB)亜型の一例
    吉田 圭佑, 薦田 宗則, 伊藤 千尋, 原口 竜摩, 北澤 理子, 北澤 荘平 日本病理学会会誌 101 (1) 441 -441 2012年03月 [無し][無し]
  • アガロースビーズ法による微小組織切片からの遺伝子解析法 胃底腺ポリープと異所性胃粘膜のβカテニン変異
    中川 みく, 牧田 憲二, 桑原 奈都美, 原口 竜摩, 北澤 理子, 北澤 荘平 日本病理学会会誌 101 (1) 441 -441 2012年03月 [無し][無し]
  • 骨形成/骨成熟過程におけるTbx18遺伝子の役割
    原口 竜摩, 北澤 理子, 北澤 荘平 日本組織細胞化学会総会・学術集会講演プログラム・予稿集 52回 74 -74 2011年09月 [無し][無し]
  • 新規遺伝子改変マウスを用いた平滑筋組織の機能破綻に起因する腎尿路疾患についての解析
    原口 竜摩, 松丸 大輔, 杉田 敦郎, 木藤 克己, 阿部 康人, 北澤 理子, 山田 源, 北澤 荘平 日本病理学会会誌 100 (1) 365 -365 2011年03月 [無し][無し]
  • 村嶋亜紀, 宮川信一, 西田尚代, 原口竜摩, 荻野由起子, 加藤茂明, 山田源 日本アンドロロジー学会総会記事 27th 124 -125 2008年06月 [無し][無し]
  • 村嶋亜紀, 宮川信一, 西田尚代, 原口竜摩, 松本高広, 荒木喜美, 山村研一, MOON Anne, 加藤茂明, 山田源 生化学 2P-1043 2008年 [無し][無し]
  • 原口竜摩, 宮川信一, 松丸大輔, 中潟直己, 山田源 日本アンドロロジー学会総会記事 26th 177 2007年06月 [無し][無し]
  • G. Yamada, K. Suzuki, R. Haraguchi, S. Miyagawa, Y. Satoh, M. Kamimura, N. Nakagata, H. Kataoka, A. Kuroiwa, Y. Chen DEVELOPMENTAL DYNAMICS 書評論文,書評,文献紹介等 235 (7) 1738 -1752 2006年07月 [無し][無し]
     
    External genitalia are anatomical structures located at the posterior embryonic region as part of several urogenital/reproductive organs. The embryonic anlage of the external genitalia, the genital tubercle (GT) develops as a bud-shaped structure with an initial urethral plate and later urethra. Embryonic external genitalia are considered to be one of the appendages. Recent experiments suggest that essential regulatory genes possess similar functions for the outgrowth regulation of the GT and limb appendages. The transient embryonic epithelia located in the distal GT are called the distal urethral epithelium (DUE) regulating, at least in part, the (distal) GT development. This review covers the available data about early patterning of GT and discusses the molecular developmental similarities and points of divergence between the different appendages. Development of the male and female external genitalia is also reviewed.
  • マウス外生殖器原基(生殖結節)に見られる伸長制御メカニズム:BMPシグナリングの機能解析
    鈴木堅太郎, 神川真美, 尾木秀直, 原口竜摩, 荻野由紀子, 山田源 細胞工学 23 (2) 208 -209 2004年01月 [無し][無し]
  • Regulation of outgrowth and apoptosis for the terminal appendage: external genitalia development by concerted actions of BMP signaling (vol 130, pg 6209, 2003)
    K Suzuki, D Bachiller, YP Chen, M Kamikawa, H Ogi, R Haraguchi, Y Ogino, Y Minami, Y Mishina, K Ahn, EB Crenshaw, G Yamada DEVELOPMENT その他 130 (26) 6643 -6643 2003年12月 [無し][無し]
  • Outgrowth and apoptosis for the external genitalia formation by concerted functions of Bmp signaling.
    K Suzuki, D Bachiller, YP Chen, M Kamikawa, H Ogi, R Haraguchi, Y Ogino, Y Mishina, K Ahn, EB Crenshaw, G Yamada DEVELOPMENTAL BIOLOGY 研究発表ペーパー・要旨(国際会議) 259 (2) 549 -549 2003年07月 [無し][無し]
  • Expression analysis on genes involved in the development of external genitalia.
    G Yamada, K Suzuki, Y Ogino, Y Sato, H Ogi, H Katoh, M Kamikawa, R Haraguchi DEVELOPMENTAL BIOLOGY 研究発表ペーパー・要旨(国際会議) 247 (2) 513 -513 2002年07月 [無し][無し]
  • 尾木秀直, 荻野由紀子, 原口竜摩, 鈴木堅太郎, 加藤洋教, 神川真美, 山田源 生物薬剤学研究会講演要旨集 20th 6 -11 2002年05月 [無し][無し]
  • Molecular analysis of external genitalia formation: Morphogenesis of limbs and genital tubercle
    R Haraguchi, K Suzuki, M Kamikawa, Y Ogino, R Murakami, M Sakai, M Kengaku, S Nakamura, Y Komatsu, N Takeda, S Kato, N Ueno, G Yamada DEVELOPMENTAL DYNAMICS 研究発表ペーパー・要旨(国際会議) 219 (3) 458 -458 2000年11月 [無し][無し]
  • 鈴木堅太郎, 原口竜摩, 竹田直樹, 萩野由紀子, 中村誠司, 小松義広, 神川真美, 佐藤義彦, 土山修治, 一鬼勉, 中潟直己, 浦野徹, 山田源 九州実験動物雑誌 16 15 -21 2000年11月 [無し][無し]
  • 鈴木堅太郎, 中村誠司, 原口竜摩, 岡田明子, 山西清文, 豊田哲也, 藤谷登, ANDERSEN B, 山田源 日本分子生物学会年会プログラム・講演要旨集 21st 606 1998年11月 [無し][無し]

受賞

  • 2019年09月 日本組織細胞化学会 日本組織細胞化学会論文賞
  • 2018年07月 日本骨代謝学会 第1回日本骨代謝学会若手研究者助成
     
    受賞者: 原口 竜摩
  • 2014年07月 日本骨代謝学会 日本骨代謝学会優秀示説演題賞
  • 2004年02月 井上科学振興財団 井上研究奨励賞

共同研究・競争的資金等の研究課題

  • 老人性骨粗鬆症の病態解析:加齢モデルにおける破骨細胞分化因子発現制御
    日本学術振興会:科学研究費 基盤研究(C)
    研究期間 : 2019年 -2021年 
    代表者 : 北澤 理子, 原口 竜
  • 成長板を発生起点とする骨髄造血ニッチ形成メカニズムの解析
    日本学術振興会:科学研究費 基盤研究(C)
    研究期間 : 2018年 -2020年 
    代表者 : 原口 竜摩
  • 非定型的DNAメチル化修飾を指標とする腫瘍初期病変の同定
    日本学術振興会:科学研究費 基盤研究(B)
    研究期間 : 2016年 -2018年 
    代表者 : 北澤 荘平, 原口 竜
  • 成長板を発生起点とする骨髄微小環境形成メカニズムの解析
    日本骨代謝学会:日本骨代謝学会 若手研究者助成
    研究期間 : 2018年 
    代表者 : 原口 竜摩
  • 破骨細胞分化因子受容体(RANK)発現制御機構の解析
    日本学術振興会:科学研究費 基盤研究(C)
    研究期間 : 2015年 -2017年 
    代表者 : 北澤 理子, 原口 竜
  • 成長軟骨板に依存する長管骨発生プロセスの理解 : 組織系譜解析によるアプローチ
    日本学術振興会:科学研究費 基盤研究(C)
    研究期間 : 2015年 -2017年 
    代表者 : 原口 竜摩
  • 雄性生殖管を基軸とする雌性生殖器の新たな発生基盤
    日本学術振興会:科学研究費 若手研究(B)
    研究期間 : 2013年 -2014年 
    代表者 : 原口 竜摩
  • 胎児性上皮組織『総排泄腔』に着目した泌尿生殖系平滑筋成分の発生研究
    日本学術振興会:科学研究費 若手研究(B)
    研究期間 : 2011年 -2012年 
    代表者 : 原口 竜摩
  • Exosome分泌調節機構の解明
    日本学術振興会:科学研究費 基盤研究(C)
    研究期間 : 2010年 -2012年 
    代表者 : 木藤 克己, 原口 竜
  • 高等哺乳類外性器形成過程の解析
    日本学術振興会:科学研究費 特別研究員奨励費
    研究期間 : 2000年 -2001年 
    代表者 : 原口 竜摩

委員歴

  • 2019年 - 現在   日本組織細胞化学会   Acta Histochem Cytochem Editorial board member
  • 2017年 - 現在   日本組織細胞化学会   評議員
  • 2016年 - 現在   日本病理学会   学術評議員
  • 2010年 - 現在   愛媛病理研究会   運営委員
  • 2017年 - 2018年   第58回日本組織細胞化学会・学術総会   事務局長

担当経験のある科目

  • 『 こころと健康 (がんの基礎)』愛媛大学
  • 病理学各論 実習『造血器系』愛媛大学
  • 病理学各論 実習『呼吸器系』愛媛大学
  • 病理学各論 実習『女性生殖器,乳腺,胎盤』愛媛大学
  • 病理学各論 実習『消化器系(消化管)』愛媛大学
  • 病理学各論 実習『心血管系』愛媛大学
  • 病理学総論 講義『腫瘍論』愛媛大学


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