研究者総覧

北澤 荘平 (キタザワ ソウヘイ)

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

研究者情報

学位

  • 医学博士(神戸大学)

ホームページURL

科研費研究者番号

  • 90186239

ORCID ID

J-Global ID

プロフィール

  • 愛媛大学医学部医学科で病理学総論、各論の講義実習を担当し、大学院医学系研究科では、分子病理学、エピジェネティクス制御機構、骨代謝に関わる研究指導を行っています。病理専門医として、病理解剖、附属病院病理診断科の診断、関連病院の病理診断も担当しています。

研究キーワード

  • 骨代謝学   エピジェネティクス   分子病理学   病理解剖学   病理診断学   

研究分野

  • ライフサイエンス / 実験病理学
  • ライフサイエンス / 人体病理学

経歴

  • 2010年06月 - 現在  愛媛大学大学院医学系研究科分子病理学講座主任教授
  • 2009年06月 - 2010年05月  神戸大学大学院医学研究科分子病理診断学分野特命教授
  • 2007年04月 - 2009年05月  神戸大学大学院医学研究科分子病理学分野准教授
  • 2001年04月 - 2007年03月  神戸大学大学院医学研究科分子病理学分野助教授
  • 2000年05月 - 2001年03月  神戸大学医学部病理学第2講座助教授
  • 1992年04月 - 2000年04月  神戸大学医学部病理学第2講座講師
  • 1990年10月 - 1992年03月  神戸大学医学部病理学第2講座助手
  • 1988年 - 1990年  国立神戸病院研究検査科主任病理医
  • 1986年04月 - 1988年09月  神戸大学医学部第2病理学講座助手

学歴

  • 1985年04月 - 1986年03月   神戸大学大学院医学研究科   病理学分野
  • 1979年04月 - 1985年03月   神戸大学   医学部医学科

所属学協会

  • 米国骨代謝学会   国際病理アカデミー   日本法医学学会   日本骨代謝学会   日本臨床細胞学会   日本癌学会   日本組織細胞化学会   日本病理学会   

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, Sohei Kitazawa
    Biochemical and biophysical research communications 2020年01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.
  • Hedgehog inhibitors suppress osteoclastogenesis in in vitro cultures, and deletion of Smo in macrophage/osteoclast lineage prevents age-related bone loss.
    Kohara Y (co-corresponding), Haraguchi R, Kitazawa R, Imai Y, Kitazawa S
    International journal of molecular sciences 2020年 [有り][無し]
     研究論文(学術雑誌)
  • Ryuma Haraguchi, Riko Kitazawa, Yukihiro Kohara, Aoi Ikedo, Yuuki Imai, Sohei Kitazawa
    International journal of molecular sciences 20 23 2019年11月 [有り][無し]
     
    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.
  • Katsunori Sakamoto, Kohei Ogawa, Kei Tamura, Yoshitomo Ueno, Hitoshi Inoue, Taro Nakamura, Jota Watanabe, Akihiro Takai, Taiji Tohyama, Hidenori Senba, Osamu Yoshida, Masanori Abe, Yoichi Hiasa, Riko Kitazawa, Sohei Kitazawa, Yasutsugu Takada
    Transplantation proceedings 51 9 3131 - 3135 2019年11月 [有り][無し]
     
    Liver cirrhosis can cause splenic artery aneurysms (SAA) that pose a threat to patients undergoing liver transplantation. However, liver transplantation with multiple visceral artery aneurysms including giant SAA caused by arterial fragility has never been reported. We describe a 36-year-old man with decompensated liver cirrhosis due to Wilson disease that was complicated by giant SAA and multiple aneurysms in the bilateral renal arteries caused by fibromuscular dysplasia (FMD). The maximal diameter of the triple snowball-shaped SAA was 11 cm. We planned a 2-stage strategy consisting of a splenectomy with distal pancreatectomy to treat the SAA and subsequent living donor liver transplantation (LDLT) to address the liver cirrhosis. This strategy was selected to prevent fatal postoperative infectious complications caused by the potential development of pancreatic fistula during simultaneous procedures and to histopathologically diagnose the arterial lesion before LDLT to promote safe hepatic artery reconstruction. However, a postoperative pancreatic fistula did not develop after a splenectomy with distal pancreatectomy, and the pathologic findings of the artery indicated FMD. The patient underwent ABO-identical LDLT with a right lobe graft donated by his brother. Other than postoperative rupture of the aneurysm in the left renal artery requiring emergency interventional radiology, the patient has remained free of any other arterial complications and continues to do well at 2 years after LDLT.
  • 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.
  • Masaki T, Tsujimoto M, Kitazawa R, Nakano E, Funasaka Y, Ichihashi M, Kitazawa S, Kakita A, Kanda F, Nishigori C
    JAAD case reports 5 3 205 - 208 2019年03月 [有り][無し]
  • Tanigawa K, Maekawa M, Kiyoi T, Nakayama J, Kitazawa R, Kitazawa S, Semba K, Taguchi T, Akita S, Yoshida M, Ishimaru K, Watanabe Y, Higashiyama S
    Journal of cellular physiology 2019年02月 [有り][無し]
  • 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)
  • Miyoshi S, Nagao T, Kukida M, Miyoshi KI, Namba C, Kitazawa S, Nakamura Y, Hamaguchi N, Higaki J
    Internal medicine (Tokyo, Japan) 57 21 3141 - 3147 2018年11月 [有り][無し]
  • 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.
  • 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]
  • Ryuma Haraguchi, Riko Kitazawa, Yuuki Imai, Sohei Kitazawa
    Histochemistry and cell biology 149 4 365 - 373 2018年04月 [有り][無し]
     
    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.
  • Amizuka N, Kitazawa S
    Histochemistry and cell biology 149 4 287 - 288 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.
  • 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]
  • Yusuke Imai, Masashi Hirooka, Yohei Koizumi, Yoshiko Nakamura, Takao Watanabe, Osamu Yoshida, Yoshio Tokumoto, Eiji Takeshita, Masanori Abe, Hiroaki Tanaka, Mie Kurata, Sohei Kitazawa, Yoichi Hiasa
    Radiology case reports 12 1 179 - 184 2017年03月 [有り][無し]
     
    A 58-year-old man was diagnosed with advanced hepatocellular carcinoma with portal vein tumor thrombosis (PVTT). The tumors were multiple and existed in both lobes. Drug-eluting beads transcatheter arterial chemoembolization (DEB-TACE) was performed for the tumors in the left lobe. Embosphere and Hepasphere were selected for embolization of the arterioportal shunt, followed by loaded epirubicin infusion into the left hepatic artery. Computed tomography showed reduction of PVTT. However, liver failure progressed, and the patient died 67 days after DEB-TACE. Autopsy showed that the beads reached the tumor thrombosis in the portal vein. The prognosis of hepatocellular carcinoma with PVTT is poor. Although there are no established treatments for unresectable PVTT, DEB-TACE might be a useful option for such cases.
  • Ryuma Haraguchi, Riko Kitazawa, Aki Murashima, Gen Yamada, Sohei Kitazawa
    ACTA HISTOCHEMICA ET CYTOCHEMICA 50 4 127 - 133 2017年 [有り][無し]
     研究論文(学術雑誌) 
    In mammals, the mullerian 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.
  • Wakita M, Edamatsu H, Li M, Emi A, Kitazawa S, Kataoka T
    Journal of Biological Chemistry 291 24 12586 - 12600 2016年06月 [有り][無し]
     研究論文(学術雑誌) 
    Phospholipase C epsilon (PLC epsilon), an effector of Ras and Rap small GTPases, plays a crucial role in inflammation by augmenting proinflammatory cytokine expression. This proinflammatory function of PLC epsilon is implicated in its facilitative role in tumor promotion and progression during skin and colorectal carcinogenesis, although their direct link remains to be established. Moreover, the molecular mechanism underlying these functions of PLC epsilon remains unknown except that PKD works downstream of PLC epsilon. Here we show by employing the colitis-induced colorectal carcinogenesis model, where Apc(Min/+) mice are administered with dextran sulfate sodium, that PLC epsilon knock-out alleviates the colitis and suppresses the following tumorigenesis concomitant with marked attenuation of proinflammatory cytokine expression. In human colon epithelial Caco2 cells, TNF-alpha induces sustained expression of proinflammatory molecules and sustained activation of nuclear factor-kappa B (NF-kappa B) and PKD, the late phases of which are suppressed by not only siRNA-mediated PLC epsilon knockdown but also treatment with a lysophosphatidic acid (LPA) receptor antagonist. Also, LPA stimulation induces these events in an early time course, suggesting that LPA mediates TNF-alpha signaling in an autocrine manner. Moreover, PLC epsilon knockdown results in inhibition of phosphorylation of I kappa B by ribosomal S6 kinase (RSK) but not by I kappa B kinases. Subcellular fractionation suggests that enhanced phosphorylation of a scaffolding protein, PEA15 (phosphoprotein enriched in astrocytes 15), downstream of the PLC epsilon-PKD axis causes sustained cytoplasmic localization of phosphorylated RSK, thereby facilitating I kappa B phosphorylation in the cytoplasm. These results suggest the crucial role of the TNF-alpha-LPA-LPA receptor-PLC epsilon-PKD-PEA15-RSK-I kappa B-NF-kappa B pathway in facilitating inflammation and inflammation-associated carcinogenesis in the colon.
  • Ryuma Haraguchi, Riko Kitazawa, Kiyoshi Mori, Ryosuke Tachibana, Hiroshi Kiyonari, Yuuki Imai, Takaya Abe, Sohei Kitazawa
    SCIENTIFIC REPORTS 6 2016年04月 [有り][無し]
     研究論文(学術雑誌) 
    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 mu CT 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.
  • Shungo Yukumi, Hideaki Suzuki, Masamitsu Morimoto, Hisayuki Shigematsu, Mikio Okazaki, Masahiro Abe, Sohei Kitazawa, Kenji Nakamura, Yoshifumi Sano
    INTERNAL MEDICINE 55 23 3491 - 3493 2016年 [有り][無し]
     研究論文(学術雑誌) 
    Pneumothorax associated with thoracic endometriosis (TE) generally occurs in women around 30 years old and it usually affects the right pleural cavity. We herein report two cases of TE associated with left-sided pneumothorax in young women. The prevalence of TE in younger patients may be underestimated if these cases are treated as spontaneous pneumothorax. Pneumothorax occurring in younger patients has not been reported to show laterality. TE-related or catamenial pneumothorax in young women must therefore represent a different clinical entity from the condition seen in older patients.
  • Ryuma Haraguchi, Riko Kitazawa, Sohei Kitazawa
    CELL AND TISSUE RESEARCH 359 2 503 - 512 2015年02月 [有り][無し]
     研究論文(学術雑誌) 
    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.
  • Yuri Kameoka, Riko Kitazawa, Kanazu Ariasu, Ryosuke Tachibana, Yosuke Mizuno, Ryuma Haraguchi, Sohei Kitazawa
    ACTA HISTOCHEMICA ET CYTOCHEMICA 48 4 115 - 124 2015年 [有り][無し]
     研究論文(学術雑誌) 
    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.
  • Masaru Kinomura, Noriaki Shimada, Mana Nishikawa, Kazuyoshi Omori, Tomoyasu Jo, Yasunori Ueda, Kenji Notohara, Riko Kitazawa, Sohei Kitazawa, Masaki Fukushima, Kenichiro Asano
    INTERNAL MEDICINE 54 23 3029 - 3033 2015年 [有り][無し]
     研究論文(学術雑誌) 
    A 68-year-old man was hospitalized and examined for renal impairment. A laboratory analysis showed hypercalcemia. Although the serum parathyroid hormone and serum 1-25(OH)(2) vitamin D3 levels were not elevated, the serum parathyroid hormone-related peptide (PTHrP) level was increased. Immunoelectrophoresis of the urine and bone marrow aspiration indicated multiple myeloma (MM). He was diagnosed with the coexistence of cast nephropathy and light chain deposition disease by a renal biopsy. Notably, PTHrP expression was detected in the myeloma cells based on immunohistochemistry and in situ hybridization. It is therefore important to examine the PTHrP concentration in MM patients with hypercalcemia.
  • Shikatani Y, Okazaki M, Sakao N, Yukumi S, Shigematsu H, Kitazawa S, Sano Y
    Annals of Thoracic and Cardiovascular Surgery 21 6 567 - 569 2015年 [有り][無し]
     研究論文(学術雑誌) 
    Granular cell tumor (GCT) is found in various organs but is rare in the mediastinum. We report a case of mediastinal GCT in a 19-year-old woman who presented with left ptosis and miosis. CT and MRI revealed a 29-mm well-circumscribed tumor located close to the first thoracic vertebra with features suggesting a neurogenic tumor. The tumor was completely excised using single-port video-assisted thoracoscopic surgery. Histopathological and immunohistochemical analysis revealed that the tumor was a benign GCT. Postoperatively, left ptosis and miosis had improved slightly. To our knowledge, this is the first report regarding mediastinal GCT presenting with preoperative Horner's syndrome.
  • Nakagawa M, Kitazawa R, Kondo T, Ninomiya K, Okita M, Haraguchi R, Kitazawa S
    Virchows Archiv : an international journal of pathology 465 3 253 - 256 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 beta-catenin gene mutation, we examined whether DGH, either sporadic or FGP-associated, is attributable to alterations of the Wnt/beta-catenin pathway. Genetic analysis revealed frequent somatic beta-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/beta-catenin pathway.
  • Mori K, Kitazawa R, Kondo T, Mori M, Hamada Y, Nishida M, Minami Y, Haraguchi R, Takahashi Y, Kitazawa S
    PLoS ONE 9 7 2014年07月 [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.
  • Kentaro Nakai, Hideki Fujii, Keiji Kono, Shunsuke Goto, Riko Kitazawa, Sohei Kitazawa, Michinori Hirata, Masami Shinohara, Masafumi Fukagawa, Shinichi Nishi
    AMERICAN JOURNAL OF HYPERTENSION 27 4 586 - 595 2014年04月 [有り][無し]
     研究論文(学術雑誌) 
    BACKGROUND Diabetic nephropathy is a major risk of end-stage kidney disease. Many complex factors relate to the progression of diabetic nephropathy. Using nonobese type 2 diabetes model rats, we confirmed that oxidative stress was a crucial factor. Because recent studies suggest that vitamin D could suppress oxidative stress, we explored whether the active vitamin D analog, maxacalcitol, could also attenuate oxidative stress and prevent the progression of diabetic nephropathy. METHODS Diabetic rats aged 20 weeks were divided into 3 groups and treated with insulin, maxacalcitol, and vehicle. At age 30 weeks, blood and urine analyses, renal histology, immunohistochemistry, real-time polymerase chain reaction, and western blot were performed. RESULTS Although maxacalcitol reduced albuminuria and mesangial matrix expansion, no significant differences were observed in blood pressure and creatinine clearance among the 3 treatment groups. Systemic and intrarenal oxidative stress was reduced by maxacalcitol therapy. Expressions of nuclear factor-kappa B and nicotinamide adenine dinucleotide phosphate oxidase in the kidney also decreased in the insulin-treated and maxacalcitol-treated groups but increased in the vehicle-alone group. In addition, the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) decreased and Kelch-like erythroid cell-derived protein with CNC homology (ECH)-associated protein 1 (Keap1) increased in the vehicle-treated group; however, these expressions were restored in the maxacalcitol- and insulin-treated groups. CONCLUSIONS It is suggested that maxacalcitol attenuates the progression of diabetic nephropathy by suppression of oxidative stress and amelioration of the Nrf2-Keap1 pathway in nonobese type 2 diabetes without significant changes in blood pressure and glomerular filtration rate.
  • Daisuke Matsumaru, Ryuma Haraguchi, Anne M. Moon, Yoshihiko Satoh, Naomi Nakagata, Ken-ichi Yamamura, Naoki Takahashi, Sohei Kitazawa, Gen Yamada
    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.
  • Takafumi Watanabe, Riko Kitazawa, Yosuke Mizuno, Natsumi Kuwahara, Chizu Ito, Atsuro Sugita, Ryuma Haraguchi, Sohei Kitazawa
    ACTA HISTOCHEMICA ET CYTOCHEMICA 47 3 125 - 131 2014年 [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.
  • Hiroaki Asai, Hiroshi Fujiwara, Sohei Kitazawa, Naoto Kobayashi, Toshiki Ochi, Yukihiro Miyazaki, Fumihiro Ochi, Yoshiki Akatsuka, Sachiko Okamoto, Junichi Mineno, Kiyotaka Kuzushima, Hiroaki Ikeda, Hiroshi Shiku, Masaki Yasukawa
    JOURNAL OF HEMATOLOGY & ONCOLOGY 7 1 2014年01月 [有り][無し]
     研究論文(学術雑誌) 
    Because WT1 is expressed in leukemia cells, the development of cancer immunotherapy targeting WT1 has been an attractive translational research topic. However, concern of this therapy still remains, since WT1 is abundantly expressed in renal glomerular podocytes. In the present study, we clearly showed that WT1-specific cytotoxic T lymphocytes (CTLs) certainly exerted cytotoxicity against podocytes in vitro; however, they did not damage podocytes in vivo. This might be due to the anatomical localization of podocytes, being structurally separated from circulating CTLs in glomerular capillaries by an exceptionally thick basement membrane.
  • Koto Fujiishi, Riko Kitazawa, Yusa Nagai, Takafumi Watanabe, Kenji Bando, Shinji Kobayashi, Yoshihiro Yakushijin, Ryuma Haraguchi, Sohei Kitazawa
    VIRCHOWS ARCHIV 464 1 121 - 124 2014年01月 [有り][無し]
  • Munenori Komoda, Riko Kitazawa, Kenji Makita, Keisuke Yoshida, Miyuki Takeji, Yoshiko Soga, Mie Kurata, Ryuma Haraguchi, Sohei Kitazawa
    DIABETES RESEARCH AND CLINICAL PRACTICE 100 2 E59 - E62 2013年05月 [有り][無し]
     研究論文(学術雑誌) 
    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. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
  • Sann Sanda Khin, Riko Kitazawa, Kyaw Htet, Hla Min Htike, Than Than Yee, Myint Aung, Ryuma Haraguchi, Sohei Kitazawa
    PATHOLOGY INTERNATIONAL 63 3 193 - 194 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 [有り][無し]
     研究論文(学術雑誌) 
    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 beta-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 beta-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 - 541 2013年01月 [有り][無し]
     研究論文(学術雑誌) 
    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. (C) 2013 Baishideng. All rights reserved.
  • Kono K, Fujii H, Nakai K, Goto S, Kitazawa R, Kitazawa S, Shinohara M, Hirata M, Fukagawa M, Nishi S
    American Journal of Nephrology 37 2 167 - 174 2013年 [有り][無し]
  • 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.
  • Ryuma Haraguchi, Daisuke Matsumaru, Naomi Nakagata, Shinichi Miyagawa, Kentaro Suzuki, Sohei Kitazawa, Gen Yamada
    PLOS ONE 7 7 2012年07月 [有り][無し]
     研究論文(学術雑誌) 
    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.
  • Hitoshi Nishizawa, Genzo Iguchi, Ayumi Murawaki, Hidenori Fukuoka, Yoshitake Hayashi, Hidesuke Kaji, Masaaki Yamamoto, Kentaro Suda, Michiko Takahashi, Yasushi Seo, Yoshihiko Yano, Riko Kitazawa, Sohei Kitazawa, Masafumi Koga, Yasuhiko Okimura, Kazuo Chihara, Yutaka Takahashi
    EUROPEAN JOURNAL OF ENDOCRINOLOGY 167 1 67 - 74 2012年07月 [有り][無し]
     研究論文(学術雑誌) 
    Background: Liver dysfunction in adult hypopituitary patients with GH deficiency (GHD) has been reported and an increased prevalence of nonalcoholic fatty liver disease (NAFLD) has been suggested. Objective: The objective of the present study was to elucidate the pathophysiology of the liver in adult hypopituitary patients with GHD. Patients and methods: We recruited 69 consecutive Japanese adult hypopituitary patients with GHD and examined the prevalence of NAFLD by ultrasonography and nonalcoholic steatohepatitis (NASH) by liver biopsy. Patients had been given routine replacement therapy except for GH. We compared these patients with healthy age-, gender-, and BMI-matched controls. We further analyzed the effect of GH replacement therapy on liver function, inflammation and fibrotic markers, and histological changes. Results: The prevalence of NAFLD in hypopituitary patients with GHD was significantly higher than in controls (77 vs 12%, P<0.001). Of 16 patients assessed by liver biopsy, 14 (21%) patients were diagnosed with NASH. GH replacement therapy significantly reduced serum liver enzyme concentrations in the patients and improved the histological changes in the liver concomitant with reduction in fibrotic marker concentrations in patients with NASH. Conclusions: Adult hypopituitary patients with GHD demonstrated a high NAFLD prevalence. The effect of GH replacement therapy suggests that the NAFLD is predominantly attributable to GHD.
  • Tomomi Sakuma, Tetsuya Nakamoto, Hiroaki Hemmi, Sohei Kitazawa, Riko Kitazawa, Takuya Notomi, Tadayoshi Hayata, Yoichi Ezura, Teruo Amagasa, Masaki Noda
    JOURNAL OF CELLULAR PHYSIOLOGY 227 7 2807 - 2812 2012年07月 [有り][無し]
     研究論文(学術雑誌) 
    Tumor metastasis to bone is a serious pathological situation that causes severe pain, and deterioration in locomoter function. However, the mechanisms underlying tumor metastasis is still incompletely understood. CIZ/NMP4 is a nucleocytoplasmic shuttling protein and its roles in tumor cells have not been known. We, therefore, hypothesized the role of CIZ/NMP4 in B16 melanoma cells that metastasize to bone. CIZ/NMP4 is expressed in B16 cells. The CIZ/NMP4 expression levels are correlated to the metastatic activity in divergent types of melanoma cells. Overexpression of CIZ/NMP4 increased B16 cell migration in Trans-well assay. Conversely, siRNA-based knockdown of CIZ/NMP4 suppressed migratory activity of these cells. As RANKL promotes metastasis of tumor cells in bone, we tested its effect on CIZ in melanoma cells. RANKL treatment enhanced CIZ/NMP4 expression. This increase of CIZ by RANKL promoted migration. Conversely, we identified CIZ/NMP4 binding site in the promoter of RANKL. Furthermore, luciferase assay indicated that CIZ/NMP4 overexpression enhanced RANKL promoter activities, revealing a positive feedback loop of CIZ/NMP4 and RANKL in melanoma. These observations indicate that CIZ/NMP4 is critical regulator of metastasis of melanoma cells. J. Cell. Physiol. 227: 28072812, 2012. (C) 2012 Wiley Periodicals, Inc.
  • Sohei Kitazawa, Takeshi Kondo, Kiyoshi Mori, Naoki Yokoyama, Masafumi Matsuo, Riko Kitazawa
    HUMAN MUTATION 33 4 651 - 654 2012年04月 [有り][無し]
     研究論文(学術雑誌) 
    We evaluated an autopsy case with severe neonatal respiratory distress, hypoplasia of thymus, thyroid gland and cerebellum, and agenesis of the corpus callosum displaying striking phenotypic similarity to the CrebA knockout mouse. On the assumption that comparable genetic alterations must be present, we checked the whole genomic DNA sequence of cyclic adenosine monophosphate (cAMP) response element binding protein 1 (CREB1), the human counterpart of mouse CrebA, and found a missense c.347A>G mutation corresponding to p.D116G within the kinase-inducible domain (KID) of CREB1. When transcribed in vitro, while Ser-133 phosphorylation of KID was maintained upon forskolin treatment, mutated CREB1 protein failed to associate with the KIX domain of co-activator CREBBP/EP300, and thereby, interrupted cAMP-dependent protein kinase A signal transduction as the dominant-negative form. This is the first report of a sporadic CREB1-related multiple malformation syndrome that, in light of accumulated knowledge of phenotypic features in gene-targeted animals, clearly emphasizes the importance of cross-species translational research. Hum Mutat 33:651654, 2012. (c) 2012 Wiley Periodicals, Inc.
  • Nagai Y, Kitazawa R, Nakagawa M, Komoda M, Kondo T, Haraguchi R, Kitazawa S
    Case reports in pathology 2012 613180  2012年 [有り][無し]
  • Toshiya Matsubara, Ayako Mita, Kohtaro Minami, Tetsuya Hosooka, Sohei Kitazawa, Kenichi Takahashi, Yoshikazu Tamori, Norihide Yokoi, Makoto Watanabe, Ei-ichi Matsuo, Osamu Nishimura, Susumu Seino
    CELL METABOLISM 15 1 38 - 50 2012年01月 [有り][無し]
     研究論文(学術雑誌) 
    Adipose tissue secretes adipokines that mediate insulin resistance, a characteristic feature of obesity and type 2 diabetes. By differential proteome analysis of cellular models of insulin resistance, we identified progranulin (PGRN) as an adipokine induced by TNF-alpha and dexamethasone. PGRN in blood and adipose tissues was markedly increased in obese mouse models and was normalized with treatment of pioglitazone, an insulin-sensitizing agent. Ablation of PGRN (Grn(-/-)) prevented mice from high fat diet (HFD)-induced insulin resistance, adipocyte hypertrophy, and obesity. Gm deficiency blocked elevation of IL-6, an inflammatory cytokine, induced by HFD in blood and adipose tissues. Insulin resistance induced by chronic administration of PGRN was suppressed by neutralizing IL-6 in vivo. Thus, PGRN is a key adipokine that mediates HFD-induced insulin resistance and obesity through production of IL-6 in adipose tissue, and may be a promising therapeutic target for obesity.
  • K. Takeuchi, T. Tsujino, M. Yabuta, S. Kitazawa
    EUROPEAN JOURNAL OF GYNAECOLOGICAL ONCOLOGY 33 5 552 - 554 2012年 [有り][無し]
     研究論文(学術雑誌) 
    Background: Ichthyosis uteri is an uncommon entity in which the entire endometrium is replaced by stratified squamous epithelium. Though the condition often is considered as benign, dysplastic changes have been reported. Case: We describe herein an exceedingly rare case of primary squamous cell carcinoma of the endometrium (PSCCE) associated with extensive ichthyosis uteri with chronic pyometra, who presented with blood-stained vaginal discharge of six-seven months duration. Although repeated endometrial biopsies revealed only strips of stratified squamous epithelium showing moderate to severe dysplastic changes, the tumor markers and magnetic resonance imaging strongly suggested advanced uterine body malignancy. Exploratory laparotomy was performed, and histologic findings of the superficial layer were consistent with ichthyosis uteri; in contrast the lesion of invasive squamous cell carcinoma was located in the deeper layer and lymph nodes. No dysplastic changes of the cervix were noted. Conclusions: It is suggested that PSCCE could be associated with pre-existing ichthyosis uteri and deeper biopsies should be performed for the accurate preoperative diagnosis of cases with chronic pyometra.
  • Takahashi M, Okimura Y, Iguchi G, Nishizawa H, Yamamoto M, Suda K, Kitazawa R, Fujimoto W, Takahashi K, Zolotaryov F.N, Hong K.S, Kiyonari H, Abe T, Kaji H, Kitazawa S, Kasuga M, Chihara K, Takahashi Y
    Scientific Reports 1 2011年10月 [有り][無し]
     研究論文(学術雑誌) 
    Although various function of chemerin have been suggested, its physiological role remains to be elucidated. Here we show that chemerin-deficient mice are glucose intolerant irrespective of exhibiting reduced macrophage accumulation in adipose tissue. The glucose intolerance was mainly due to increased hepatic glucose production and impaired insulin secretion. Chemerin and its receptor ChemR23 were expressed in beta-cell. Studies using isolated islets and perfused pancreas revealed impaired glucose-dependent insulin secretion (GSIS) in chemerin-deficient mice. Conversely, chemerin transgenic mice revealed enhanced GSIS and improved glucose tolerance. Expression of MafA, a pivotal transcriptional factor for beta-cell function, was downregulated in chemerin-deficient islets and a chemerin-ablated beta-cell line and rescue of MafA expression restored GSIS, indicating that chemerin regulates beta-cell function via maintaining MafA expression. These results indicate that chemerin regulates beta-cell function and plays an important role in glucose homeostasis in a tissue-dependent manner.
  • Esposito F, Boscia F, Franco R, Tornincasa M, Fusco A, Kitazawa S, Looijenga L.H, Chieffi P
    Journal of Pathology 224 1 110 - 120 2011年05月 [有り][無し]
     研究論文(学術雑誌) 
    Oestrogen exposure has been linked to a risk for the development of testicular germ cell cancers. The effects of oestrogen are now known to be mediated by oestrogen receptor-alpha (ER alpha) and ER beta subtypes, but only ER beta has been found in human germ cells of normal testis. However, its expression was markedly diminished in seminomas, embryonal cell carcinomas and mixed germ cell tumours, but remains high in teratomas. PATZ1 is a recently discovered zinc finger protein that, due to the presence of the POZ domain, acts as a transcriptional repressor affecting the basal activity of different promoters. We have previously described that PATZ1 plays a crucial role in normal male gametogenesis and that its up-regulation and mislocalization could be associated with the development of testicular germ cell tumours. Here we show that ER beta interacts with PATZ1 in normal germ cells, while down-regulation of ER beta associates with transcriptional co-regulator PATZ1 delocalization in human testicular seminomas. In addition, we show that the translocation of PATZ1 from the cytoplasm into the nucleus is regulated by cAMP, which also induces increased expression and nuclear localization of ER beta, while this effect is counteracted by using the anti-oestrogen ICI 182-780. Copyright (C) 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
  • Mukai S, Kitazawa R, Ishii J, Kondo T, Hakozaki A, Horiuchi K, Haraguch R, Mori K, Kitazawa S
    Molecular and Cellular Biochemistry 350 1-2 29 - 38 2011年04月 [有り][無し]
     研究論文(学術雑誌) 
    Receptor activator of NF-kappa B (RANK) is a member of the tumor necrosis factor receptor (TNFR) family expressed in osteoclast precursors, and RANK-RANK ligand (RANKL) signaling is a key system for differentiation, activation and survival of osteoclasts. Here, we report the identification of a novel alternative splicing variant of mouse RANK gene (vRANK) that contains a new intervening exon between exon 1 and exon 2 of mouse full-length RANK (fRANK) mRNA. Since this novel exon contains the stop codon, vRANK encodes truncated amino acids that have a portion of the signal peptide of fRANK and an additional 19 amino acids that show no homology to previously reported domains. By transient transfection studies with vRANK-GFP and -Flag expressing constructs, vRANK was found localized mostly in the cytoplasm and partly in the cell membrane, but was not secreted into the culture supernatant. Under the stimulation of various factors, the expression of vRANK mRNA was almost parallel to that of fRANK in RAW264.7 cells not treated with M-CSF. Overexpression of vRANK, on the other hand, decreased TRACP (a marker of osteoclasts) mRNA expression as well as the number of TRACP-positive multinucleated giant cells. While the mRNA expression levels of NFATc1 (a master transcriptional factor of the osteoclast differentiation program) were not affected, apoptotic cells increased significantly in vRAN K-transfected cells treated with sRANKL. Taken together, these results suggest that vRANK is a novel osteoclast suppressor that reduces the number of RANKL-induced mature osteoclasts mainly by negating the anti-apoptotic effect of RANKL.
  • Khin S.S, 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.
  • Itoko Hisa, Yoshifumi Inoue, Geoffrey N. Hendy, Lucie Canaff, Riko Kitazawa, Sohei Kitazawa, Toshihisa Komori, Toshitsugu Sugimoto, Susumu Seino, Hiroshi Kaji
    JOURNAL OF BIOLOGICAL CHEMISTRY 286 11 9787 - 9796 2011年03月 [有り][無し]
     研究論文(学術雑誌) 
    The mechanisms whereby the parathyroid hormone (PTH) exerts its anabolic action on bone are incompletely understood. We previously showed that inhibition of ERK1/2 enhanced Smad3-induced bone anabolic action in osteoblasts. These findings suggested the hypothesis that changes in gene expression associated with the altered Smad3-induced signaling brought about by an ERK1/2 inhibitor would identify novel bone anabolic factors in osteoblasts. We therefore performed a comparative DNA microarray analysis between empty vector-transfected mouse osteoblastic MC3T3-E1 cells and PD98059-treated stable Smad3-overexpressing MC3T3-E1 cells. Among the novel factors, Tmem119 was selected on the basis of its rapid induction by PTH independent of later increases in endogenous TGF-beta. The levels of Tmem119 increased with time in cultures of MC3T3-E1 cells and mouse mesenchymal ST-2 cells committed to the osteoblast lineage by BMP-2. PTH stimulated Tmem119 levels within 1 h as determined by Western blot analysis and immunocytochemistry in MC3T3-E1 cells. MC3T3-E1 cells stably overexpressing Tmem119 exhibited elevated levels of Runx2, osteocalcin, alkaline phosphatase, and beta-catenin, whereas Tmem119 augmented BMP-2-induced Runx2 levels in mesenchymal cells. Tmem119 interacted with Runx2, Smad1, and Smad5 in C2C12 cells. In conclusion, we identified a Smad3-related factor, Tmem119, that is induced by PTH and promotes differentiation in mouse osteoblastic cells. Tmem119 is an important molecule in the pathway downstream of PTH and Smad3 signaling in osteoblasts.
  • S. Ued, S. Kitazawa, K. Ishida, Y. Nishikawa, M. Matsui, H. Matsumoto, T. Aoki, S. Nozaki, T. Takeda, Y. Tamori, A. Aiba, C. Kahn, T. Kataoka, T. Satoh
    MOLECULAR BIOLOGY OF THE CELL 22 7 2254 - 61 2011年 [有り][無し]
  • S. Ued, S. Kitazawa, K. Ishida, Y. Nishikawa, M. Matsui, H. Matsumoto, T. Aoki, S. Nozaki, T. Takeda, Y. Tamori, A. Aiba, C. Kahn, T. Kataoka, T. Satoh
    MOLECULAR BIOLOGY OF THE CELL 22 7 2254 - 2261 2011年 [有り][無し]
  • Koma Y, Matsuoka H, Ryoke T, Koyama M, Fukumitsu K, Kasai Y, Masuya D, Yoshimatsu H, Kitazawa S, Suzuki Y
    Nihon Koky?ki Gakkai zasshi = the journal of the Japanese Respiratory Society 49 8 577 - 582 2011年 [有り][無し]
  • Shunsuke Goto, Hideki Fujii, Keiji Kono, Kentaro Nakai, Yasuhiro Hamada, Hideyuki Yamato, Masami Shinohara, Riko Kitazawa, Sohei Kitazawa, Shinichi Nishi, Masafumi Fukagawa
    AMERICAN JOURNAL OF NEPHROLOGY 34 3 281 - 290 2011年 [有り][無し]
     研究論文(学術雑誌) 
    Background: Diabetic bone disease is a major complication in diabetes mellitus and is characterized by low-turnover bone formation. Recent studies have demonstrated that oxidative stress could be associated with diabetic bone disease and that beta-adrenergic antagonists could increase bone formation. Our study investigated the effect of carvedilol (beta-blocker), possessing an antioxidant effect, on diabetic bone disease. Methods: We used the non-obese, type 2 diabetes model Spontaneously Diabetic Torii (SDT) rats in this study. Sprague-Dawley rats were used as controls (control, n = 6). SDT rats were divided into four groups: diabetic (DM, n = 8), DM+insulin (DM+I, n = 7), DM+carvedilol (DM+C, n = 8), and DM+N-acetylcysteine (DM+N, n = 10) at 20 weeks. The rats were sacrificed at 30 weeks, after which blood and urine samples, bone mineral density, histomorphometry, and oxidative stress were evaluated. Results: The number of 8-hydroxydeoxyguanosine-positive cells in bone tissue was significantly lower in the DM+C and DM+N groups than in the DM group. Mineral apposition rate and bone formation rate per bone surface in the DM+C and DM+N groups were significantly higher than those in the DM group, and these parameters were better in the DM+C group than in the DM+N group. Conclusion: Our data suggest that carvedilol has stronger effects on diabetic low-turnover bone disease beyond that which can be attributed to its antioxidative stress mechanism. Copyright (C) 2011 S. Karger AG, Basel
  • Hamada Y, Kitazawa S, Kitazawa R, Kono K, Goto S, Komaba H, Fujii H, Yamamoto Y, Yamamoto H, Usami M, Fukagawa M
    Endocrine 38 3 369 - 376 2010年12月 [有り][無し]
  • Yasuhiro Hamada, Sohei Kitazawa, Riko Kitazawa, Keiji Kono, Shunsuke Goto, Hirotaka Komaba, Hideki Fujii, Yasuhiko Yamamoto, Hiroshi Yamamoto, Makoto Usami, Masafumi Fukagawa
    ENDOCRINE 38 3 369 - 376 2010年12月 [有り][無し]
     研究論文(学術雑誌) 
    It has been reported that AGEs and the receptor for AGEs (RAGEs) have been linked to the pathogenesis of diabetic microangiopathy. However, the relationship between RAGE and alteration in bone metabolism is unclear. Therefore, in order to determine the role of RAGE in bone metabolism, we investigated the effects of RAGE deletion on bone metabolism under physiological and diabetic conditions using RAGE knockout mice (RAGE-KO). Eight-week-old male RAGE-KO and wild-type littermates (WT) were intraperitoneally injected with either streptozotocin or vehicle. Mice were classified into four groups: (1) nondiabetic WT; (2) nondiabetic RAGE-KO; (3) diabetic WT; and (4) diabetic RAGE-KO. After 12 weeks of streptozotocin or vehicle treatment, the physical properties of femora and the static and dynamic parameters of bone histomorphometry of tibiae were assessed. The deletion of RAGE affected neither body weights nor hemoglobin A1c levels. RAGE deletion resulted in increased bone mineral density due to decreased osteoclast function under physiological conditions that is no accumulation of AGEs. In contrast, lacking RAGE did not affect the alteration in bone metabolism under diabetic conditions, suggesting that AGEs-RAGE interaction may not be involved in the pathogenesis of diabetic osteopenia, although RAGE plays a crucial role in bone metabolism.
  • Maki Yabuta, Kyousuke Takeuchi, Sohei Kitazawa, Hiroki Morita
    INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS 111 2 181 - 182 2010年11月 [有り][無し]
  • N. C. Goddard, A. McIntyre, D. Gilbert, S. Kitazawa, J. Shipley
    GENES CHROMOSOMES & CANCER 49 10 963 - 966 2010年10月 [有り][無し]
  • N. C. Goddard, A. McIntyre, D. Gilbert, S. Kitazawa, J. Shipley
    GENES CHROMOSOMES & CANCER 49 10 963 - 966 2010年10月 [有り][無し]
  • Shuji Ueda, Sohei Kitazawa, Kota Ishida, Yuki Nishikawa, Megumi Matsui, Hikaru Matsumoto, Takuji Aoki, Shinsuke Nozaki, Tomoya Takeda, Yoshikazu Tamori, Atsu Aiba, C. Ronald Kahn, Tohru Kataoka, Takaya Satoh
    FASEB JOURNAL 24 7 2254 - 2261 2010年07月 [有り][無し]
     研究論文(学術雑誌) 
    The Rho family GTPase Rac1 has been implicated in the regulation of glucose uptake in myoblast cell lines. However, no evidence for the role of Rac1 has been provided by a mouse model. The purpose of this study is to test the involvement of Rac1 in insulin action in mouse skeletal muscle. Intravenous administration of insulin indeed elicited Rac1 activation in gastrocnemius muscle, suggesting the involvement of Rac1 in this signaling pathway. We then examined whether insulin-stimulated translocation of the facilitative glucose transporter GLUT4 from its storage sites to the skeletal muscle sarcolemma depends on Rac1. We show that ectopic expression of constitutively activated Rac1, as well as intravenous administration of insulin, caused translocation of GLUT4 to the gastrocnemius muscle sarcolemma, as revealed by immunofluorescent staining of a transiently expressed exofacial epitope-tagged GLUT4 reporter. Of particular note, insulin-dependent, but not constitutively activated Rac1-induced, GLUT4 translocation was markedly suppressed in skeletal muscle-specific rac1-knockout mice compared to control mice. Immunogold electron microscopic analysis of endogenous GLUT4 gave similar results. Collectively, we propose a critical role of Rac1 in insulin-dependent GLUT4 translocation to the skeletal muscle sarcolemma, which has heretofore been predicted solely by cell culture studies.-Ueda, S., Kitazawa, S., Ishida, K., Nishikawa, Y., Matsui, M., Matsumoto, H., Aoki, T., Nozaki, S., Takeda, T., Tamori, Y., Aiba, A., Kahn, C. R., Kataoka, T., Satoh, T. Crucial role of the small GTPase Rac1 in insulin-stimulated translocation of glucose transporter 4 to the mouse skeletal muscle sarcolemma. FASEB J. 24, 2254-2261 (2010). www.fasebj.org
  • GH and IGF-I ameliorate inflammation and fibrosis in a mouse model of non alcoholic steatohepatitis
    Nishizawa Hitoshi, Iguchi Genzo, Takahashi Michiko, Yamamoto Masaaki, Handayaningsih, Anastasia-Evi, Kitazawa Riko, Okimura Yasuhiko, Kaji Hidesuke, Kitazawa Sohei, Hayashi Yoshitake, Chihara Kazuo, Seino Susumu, Takahashi Yutaka
    ENDOCRINE JOURNAL 57 S520  2010年03月 [有り][無し]
  • Hideki Fujii, Keiji Kono, Kentaro Nakai, Shunsuke Goto, Hirotaka Komaba, Yasuhiro Hamada, Masami Shinohara, Riko Kitazawa, Sohei Kitazawa, Masafumi Fukagawa
    AMERICAN JOURNAL OF NEPHROLOGY 31 4 342 - 352 2010年 [有り][無し]
     研究論文(学術雑誌) 
    Background: The role of nitric oxide (NO) is controversial in diabetes nephropathy progression and the mechanisms remain unknown, especially in non-obese type 2 diabetes. To examine mechanisms of nephropathy progression in nonobese type 2 diabetes, we used spontaneously diabetic Torii (SDT) rats, a newly established model of non-obese type 2 diabetes. Methods: Fourteen male Sprague-Dawley rats were used as a control (20 weeks, n = 6; 30 weeks, n = 8), and 20-week-old male SDT rats were divided into 2 groups: diabetic (DM, n = 8) and DM + insulin (n = 8) groups. Twenty-and 36-week-old rats were sacrificed, and blood, urine, and histomorphometric analyses, mRNA expression analysis of endothelial NO synthase (eNOS) and NADPH oxidase, and blood pressure measurement were performed. Results: At 36 weeks, NO metabolites, and 8-hydroxydeoxyguanosine (8-OHdG) were significantly higher in the diabetic group than in the other 2 groups. Further renal studies showed in creased glomerular volume and mesangial area, and intensified eNOS, 8-OHdG, and nitrotyrosine immunostaining in the diabetic group. Oxidative and nitrosative stress were positively associated with increased glomerular volume and mesangial area, which were mostly recovered by insulin therapy. Conclusions: NO and oxidative stress increased in SDT rats, suggesting that these play key roles in nephropathy progression in non-obese type 2 diabetes. Copyright (C) 2010 S. Karger AG, Basel
  • Hideki Fujii, Keiji Kono, Kentaro Nakai, Shunsuke Goto, Hirotaka Komaba, Yasuhiro Hamada, Masami Shinohara, Riko Kitazawa, Sohei Kitazawa, Masafumi Fukagawa
    AMERICAN JOURNAL OF NEPHROLOGY 31 4 342 - 352 2010年 [有り][無し]
     研究論文(学術雑誌) 
    Background: The role of nitric oxide (NO) is controversial in diabetes nephropathy progression and the mechanisms remain unknown, especially in non-obese type 2 diabetes. To examine mechanisms of nephropathy progression in nonobese type 2 diabetes, we used spontaneously diabetic Torii (SDT) rats, a newly established model of non-obese type 2 diabetes. Methods: Fourteen male Sprague-Dawley rats were used as a control (20 weeks, n = 6; 30 weeks, n = 8), and 20-week-old male SDT rats were divided into 2 groups: diabetic (DM, n = 8) and DM + insulin (n = 8) groups. Twenty-and 36-week-old rats were sacrificed, and blood, urine, and histomorphometric analyses, mRNA expression analysis of endothelial NO synthase (eNOS) and NADPH oxidase, and blood pressure measurement were performed. Results: At 36 weeks, NO metabolites, and 8-hydroxydeoxyguanosine (8-OHdG) were significantly higher in the diabetic group than in the other 2 groups. Further renal studies showed in creased glomerular volume and mesangial area, and intensified eNOS, 8-OHdG, and nitrotyrosine immunostaining in the diabetic group. Oxidative and nitrosative stress were positively associated with increased glomerular volume and mesangial area, which were mostly recovered by insulin therapy. Conclusions: NO and oxidative stress increased in SDT rats, suggesting that these play key roles in nephropathy progression in non-obese type 2 diabetes. Copyright (C) 2010 S. Karger AG, Basel
  • Takashi Sasayama, Katsu Mizukawa, Yoshio Sakagami, Takashi Mizowaki, Kazuhiro Tanaka, Chiho Ohbayashi, Kiyoshi Mori, Sohei Kitazawa, Eiji Kohmura
    NEUROLOGIA MEDICO-CHIRURGICA 49 11 532 - 535 2009年11月 [有り][無し]
     研究論文(学術雑誌) 
    A 54-year-old man with Klinefelter syndrome presented with glioblastoma multiforme manifesting as a 2-week history of motor weakness of the bilateral extremities. Magnetic resonance imaging showed multiple heterogeneously enhanced tumors in the bilateral frontal lobes. Angiography showed no tumor stain or arteriovenous shunt. The tumor was partially removed through a right craniotomy. The histological diagnosis was glioblastoma. Immunohistochemical examination showed no O(6)-methylguaninedeoxyribonucleic acid methyltransferase protein expression. Postoperative local radiotherapy (60 Gy/30 fractions) combined with temozolomide (75 mg/m(2) x 42 days) and interferon-beta (3,000,000 U, 3 times/week) was performed. The patient's clinical status rapidly deteriorated during chemoradiotherapy, and he died of tumor progression 3.5 months after the surgery. Postmortem examination revealed widespread glioblastoma infiltrating the basal ganglia and thalamus. Klinefelter syndrome is associated with increased cancer predisposition, especially for male breast cancer and germ cell tumors, but glioma is extremely rare. The abnormal genetic constitution of this patient may have been directly responsible for the poor outcome.
  • Li M, Edamatsu H, Kitazawa R, Kitazawa S, Kataoka T
    Carcinogenesis 30 8 1424 - 1432 2009年08月 [有り][無し]
     研究論文(学術雑誌) 
    Apc(Min/+) mice, carrying an inactivated allele of the adenomatous polyposis coli gene, are widely used as an animal model for human colorectal tumorigenesis, where tumor environment, such as inflammation, is known to play a critical role in tumor progression. We previously demonstrated that phospholipase C (PLC)epsilon, an effector of Ras and Rap small GTPases, plays a crucial role in two-stage skin chemical carcinogenesis using 12-O-tetradecanoyl-phorbor-13-acetate (TPA) as a promoter through augmentation of TPA-induced inflammation. Here, we show that Apc(Min/+) mice lacking PLC epsilon (PLC epsilon(-/-)) exhibit marked resistance to spontaneous intestinal tumorigenesis compared with those with the PLC epsilon(+/+) background. Time course of the development of tumors, which are histopathologically classified into low- and high-grade adenomas with increasing dysplasia and size, and adenocarcinomas indicates that not only the low-grade adenoma formation but also the progression to high-grade adenoma are suppressed in PLC epsilon(-/-);Apc(Min/+) mice. Low-grade adenomas of PLC epsilon(-/-);Apc(Min/+) mice exhibit accelerated apoptosis and reduced cellular proliferation. They also show marked attenuation of tumor angiogenesis and reduction in expression of vascular endothelial growth factor. In contrast, high-grade adenomas of PLC epsilon(-/-);Apc(Min/+) mice exhibit marked attenuation of tumor-associated inflammation without significant differences in apoptosis and proliferation. These results suggest that PLC epsilon plays crucial roles in intestinal tumorigenesis through two distinct mechanisms, augmentation of angiogenesis and inflammation, depending on the tumor stage.
  • Mingzhen Li, Hironori Edamatsu, Riko Kitazawa, Sohei Kitazawa, Tohru Kataoka
    CARCINOGENESIS 30 8 1424 - 1432 2009年08月 [有り][無し]
     研究論文(学術雑誌) 
    Apc(Min/+) mice, carrying an inactivated allele of the adenomatous polyposis coli gene, are widely used as an animal model for human colorectal tumorigenesis, where tumor environment, such as inflammation, is known to play a critical role in tumor progression. We previously demonstrated that phospholipase C (PLC)epsilon, an effector of Ras and Rap small GTPases, plays a crucial role in two-stage skin chemical carcinogenesis using 12-O-tetradecanoyl-phorbor-13-acetate (TPA) as a promoter through augmentation of TPA-induced inflammation. Here, we show that Apc(Min/+) mice lacking PLC epsilon (PLC epsilon(-/-)) exhibit marked resistance to spontaneous intestinal tumorigenesis compared with those with the PLC epsilon(+/+) background. Time course of the development of tumors, which are histopathologically classified into low- and high-grade adenomas with increasing dysplasia and size, and adenocarcinomas indicates that not only the low-grade adenoma formation but also the progression to high-grade adenoma are suppressed in PLC epsilon(-/-);Apc(Min/+) mice. Low-grade adenomas of PLC epsilon(-/-);Apc(Min/+) mice exhibit accelerated apoptosis and reduced cellular proliferation. They also show marked attenuation of tumor angiogenesis and reduction in expression of vascular endothelial growth factor. In contrast, high-grade adenomas of PLC epsilon(-/-);Apc(Min/+) mice exhibit marked attenuation of tumor-associated inflammation without significant differences in apoptosis and proliferation. These results suggest that PLC epsilon plays crucial roles in intestinal tumorigenesis through two distinct mechanisms, augmentation of angiogenesis and inflammation, depending on the tumor stage.
  • Hideki Fujii, Fuyuhiko Nishijima, Sumie Goto, Mikio Sugano, Hideyuki Yamato, Riko Kitazawa, Sohei Kitazawa, Masafumi Fukagawa
    NEPHROLOGY DIALYSIS TRANSPLANTATION 24 7 2089 - 2095 2009年07月 [有り][無し]
     研究論文(学術雑誌) 
    Methods. Male Lewis rats were administered adriamycin at 8 weeks of age, and the right kidney was removed at 12 weeks of age. From 14 weeks of age, the rats were treated daily with AST-120 (n = 8) or were untreated (control group, n = 8). At 34 weeks of age, the rats were killed and urinary and blood biochemical tests as well as cardiac histological analyses were performed. Results. At 14 weeks of age, there were no significant differences in blood pressure, renal function (creatinine clearance: 1.54 +/- 0.28 mL/min versus 1.60 +/- 0.22 mL/min), oxidative stress markers or other biochemical data between the control and AST-120 groups. At 34 weeks, despite similar blood pressure and renal function (creatinine clearance: 0.78 +/- 0.46 mL/min versus 0.75 +/- 0.54 mL/min), serum concentrations of IS and urinary excretion of 8-hydroxydeoxyguanosine (8-OHdG), acrolein and IS were significantly lower in the AST-120 group than in the control group. Heart volume, left ventricular volume and cardiac fibrosis were significantly smaller in the experimental AST-120 group than in the control group. Immunohistological analysis revealed that the numbers of 8-OHdG- and acrolein-positive cardiomyocytes and the degrees of myocardial and perivascular fibrosis were ameliorated by AST-120 administration. The myocardial fibrosis score was significantly associated with the 8-OHdG- (r = 0.848, P < 0.001) and acrolein-positive (r = 0.812, P < 0.001) cell scores. The perivascular fibrosis score was also significantly associated with the 8-OHdG- (r = 0.906, P < 0.0001) and acrolein-positive (r = 0.789, P < 0.001) cell scores. Conclusions. Oxidative stress is suggested to play a key role in the development of cardiac hypertrophy and fibrosis in CKD. AST-120 may suppress oxidative stress and reduce cardiac damage in CKD.
  • Sann Sanda Khin, Riko Kitazawa, Ne Win, Than Than Aye, Kiyoshi Mori, Takeshi Kondo, Sohei Kitazawa
    INTERNATIONAL JOURNAL OF CANCER 125 2 328 - 338 2009年07月 [有り][無し]
     研究論文(学術雑誌) 
    The bone morphogenetic protein (BMP) and activin membrane-bound inhibitor (BAMBI) is a transmembrane TGFRI/BMPRI-related pseudoreceptor, antagonizes transforming growth factor (TGF)-beta/BMP signaling by inhibiting the formation of functional authentic receptor complexes (TGFRI/BMPRI and TGFRII/BMPRII). On the assumption that BAMBI gene expression is epigenetically altered during human bladder cancer progression, we screened the expression of BAMBI protein by immunohistochemistry and the methylation status of the BAMBI promoter. In the normal or reactive urothelium, BAMBI expression was mostly overlapped with that of BMPRI, and a similar colocalization pattern was noted in low-grade papillary cancers. In high-grade and invasive cancers, however, mainly two reciprocal immunohistochemical expression patterns were observed: BAMBI-low/BMPRI-high, and BAMBI-high/BMPRI-low, indicating that BAMBI expression is controlled such that it does not interfere with the responsiveness of high-grade cancer cells to TGF-beta/BMP signaling. Moreover, methylation of the BAMBI gene correlated significantly with negative BAMBI expression in bladder tumors. Although BAMBI overexpression significantly increased the number of apoptotic cells in T24 line, knock-down small interfering RNA showed no remarkable change. Cell motility assay revealed that on treatment with either TGF-beta 1 or BMP2, T24 and HTB9 lines showed a marked increase in the number of migrated cells which,, however, decreased significantly through the forced expression of BAMBI. Since certain subsets of aggressive tumors often promote cell motility, invasion and survival by inducing epithelial-to-mesenchymal transition through TGF-beta/BMP in an autocrine and paracrine manner, hypermethylation of the BAMBI gene promoter that leads to BAMBI gene suppression may be one of the epigenetic events affecting the invasiveness or aggressiveness of bladder cancers. (C) 2009 UICC
  • Yasuhiro Hamada, Hideki Fujii, Riko Kitazawa, Junji Yodoi, Sohei Kitazawa, Masafumi Fukagawa
    BONE 44 5 936 - 941 2009年05月 [有り][無し]
     研究論文(学術雑誌) 
    Diabetes mellitus is associated with increased risk of osteopenia and bone fracture. However, the mechanisms accounting for diabetic bone disorder are unclear. We have previously reported that streptozotocin-induced diabetic mice develop low turnover osteopenia associated with increased oxidative stress in the diabetic condition. To determine the role of oxidative stress in the development of diabetic osteopenia, we presently investigated the effect of overexpression of thioredoxin-1 (TRX), a major intracellular antioxidant, on the development of diabetic osteopenia, using TRX transgenic mice (TRX-Tg). TRX-Tg are C57BL/6 mice that carry the human TRX transgene under the control of beta-actin promoter. Eight-week-old male TRX-Tg mice and wild type (WT) littermates were intraperitoneally injected with either streptozotocin or vehicle. Mice were grouped as 1) non-diabetic WT, 2) non-diabetic TRX-Tg, 3) diabetic WT, and 4) diabetic TRX-Tg. After 12 weeks of streptozotocin treatment, oxidative stress on the whole body and bone was evaluated, and the physical properties of the femora, and histomorphometry parameters of the tibiae were assessed. TRX overexpression did not affect either body weight or hemoglobin A1c levels. There were no significant differences in renal function and in serum levels of calcium, phosphate, and intact parathyroid hormone among the four groups. Oil the other hand, urinary excretion of 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative DNA damage, was significantly elevated in diabetic WT and attenuated in diabetic TRX-Tg. Immunohistochemical staining for 8-OHdG revealed marked intensity in the bone tissue of diabetic WT compared with non-diabetic WT while staining was attenuated in diabetic TRX-Tg. TRX overexpression partially restored reduced bone mineral density and prevented the suppression of bone formation observed in diabetic WT. Increased oxidative stress in diabetic condition contributes to the development of diabetic osteopenia. Suppression of increased oxidative stress by TRX induction could be a potential therapeutic approach for diabetic osteopenia. (C) 2008 Elsevier Inc. All rights reserved.
  • Yasuhiro Hamada, Hideki Fujii, Riko Kitazawa, Junji Yodoi, Sohei Kitazawa, Masafumi Fukagawa
    BONE 44 5 936 - 941 2009年05月 [有り][無し]
     研究論文(学術雑誌) 
    Diabetes mellitus is associated with increased risk of osteopenia and bone fracture. However, the mechanisms accounting for diabetic bone disorder are unclear. We have previously reported that streptozotocin-induced diabetic mice develop low turnover osteopenia associated with increased oxidative stress in the diabetic condition. To determine the role of oxidative stress in the development of diabetic osteopenia, we presently investigated the effect of overexpression of thioredoxin-1 (TRX), a major intracellular antioxidant, on the development of diabetic osteopenia, using TRX transgenic mice (TRX-Tg). TRX-Tg are C57BL/6 mice that carry the human TRX transgene under the control of beta-actin promoter. Eight-week-old male TRX-Tg mice and wild type (WT) littermates were intraperitoneally injected with either streptozotocin or vehicle. Mice were grouped as 1) non-diabetic WT, 2) non-diabetic TRX-Tg, 3) diabetic WT, and 4) diabetic TRX-Tg. After 12 weeks of streptozotocin treatment, oxidative stress on the whole body and bone was evaluated, and the physical properties of the femora, and histomorphometry parameters of the tibiae were assessed. TRX overexpression did not affect either body weight or hemoglobin A1c levels. There were no significant differences in renal function and in serum levels of calcium, phosphate, and intact parathyroid hormone among the four groups. Oil the other hand, urinary excretion of 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative DNA damage, was significantly elevated in diabetic WT and attenuated in diabetic TRX-Tg. Immunohistochemical staining for 8-OHdG revealed marked intensity in the bone tissue of diabetic WT compared with non-diabetic WT while staining was attenuated in diabetic TRX-Tg. TRX overexpression partially restored reduced bone mineral density and prevented the suppression of bone formation observed in diabetic WT. Increased oxidative stress in diabetic condition contributes to the development of diabetic osteopenia. Suppression of increased oxidative stress by TRX induction could be a potential therapeutic approach for diabetic osteopenia. (C) 2008 Elsevier Inc. All rights reserved.
  • Kusama T, Kodaka T, Tsunemine H, Akasaka H, Koizumi N, Fujimoto K, Sakano S, Ito R, Kondo T, Kitazawa S, Yamamura H, Takahashi K
    Gan To Kagaku Ryoho 36 3 475 - 8 2009年 [有り][無し]
  • K. Takeuchi, T. Tsujino, R. Yasumizu, S. Kitazawa
    EUROPEAN JOURNAL OF GYNAECOLOGICAL ONCOLOGY 30 6 707 - 710 2009年 [有り][無し]
     研究論文(学術雑誌) 
    Background: Lobular endocervical glandular hyperplasia (LEGH) is a rare entity of a pseudoneoplastic benign condition of the uterine cervix, and its histogenesis and pathological significance including a connection with carcinogenesis of the endocervical gland has not yet been fully recognized. Case: We describe a rare case of localized LEGH, which developed adjacent to a cesarean section scar. A 53-year-old premenopausal woman presented with a recent onset of abdominal distention and menorrhagia. Magnetic resonance imaging revealed multiple uterine myomas including submucosal myoma and localized small cystic lesions in the proximal area of the anterior wall of the cervix. Total hysterectomy was performed. The cystic lesions were diagnosed as LEGH. Thread-like foreign bodies and inflammatory reaction were demonstrated around several hyperplastic lesions. Focal immunoreactivity for MIB-1 was detected only in the LEGH cells adjacent to the fibrosis and foreign body reaction. Discussion: The histological findings, in relation to the previous cesarean section suggest that the ectopic pyloric hyperplasia in the present case could represent a heteroplastic or metaplastic process due to a multidirectional differentiation of cervical glands during chronic inflammation by foreign bodies.
  • K. Takeuchi, T. Tsujino, R. Yasumizu, S. Kitazawa
    EUROPEAN JOURNAL OF GYNAECOLOGICAL ONCOLOGY 30 6 707 - 710 2009年 [有り][無し]
     研究論文(学術雑誌) 
    Background: Lobular endocervical glandular hyperplasia (LEGH) is a rare entity of a pseudoneoplastic benign condition of the uterine cervix, and its histogenesis and pathological significance including a connection with carcinogenesis of the endocervical gland has not yet been fully recognized. Case: We describe a rare case of localized LEGH, which developed adjacent to a cesarean section scar. A 53-year-old premenopausal woman presented with a recent onset of abdominal distention and menorrhagia. Magnetic resonance imaging revealed multiple uterine myomas including submucosal myoma and localized small cystic lesions in the proximal area of the anterior wall of the cervix. Total hysterectomy was performed. The cystic lesions were diagnosed as LEGH. Thread-like foreign bodies and inflammatory reaction were demonstrated around several hyperplastic lesions. Focal immunoreactivity for MIB-1 was detected only in the LEGH cells adjacent to the fibrosis and foreign body reaction. Discussion: The histological findings, in relation to the previous cesarean section suggest that the ectopic pyloric hyperplasia in the present case could represent a heteroplastic or metaplastic process due to a multidirectional differentiation of cervical glands during chronic inflammation by foreign bodies.
  • Kitazawa S, Mori K, Kondo T, Kitazawa R
    Cases Journal 2 8 2009年 [有り][無し]
  • Kitazawa S, Kitazawa R, Kondo T, Mori K, Matsui T, Watanabe H, Watanabe M
    Cases Journal 2 11 2009年 [有り][無し]
  • Kondo T, Kitazawa R, Kawata E, Mori K, Kitazawa S
    Cases Journal 2 12 2009年 [有り][無し]
  • Kitazawa R, Yamamichi F, Hidaka T, Morishita S, Kondo T, Mori K, Kitazawa S
    Cases Journal 2 9 2009年 [有り][無し]
  • An C, Ide Y.-H, Nagano-Fujii M, Kitazawa S, Shoji I, Hotta H
    Kobe Journal of Medical Sciences 55 4 2009年 [有り][無し]
  • Kusama T, Kodaka T, Tsunemine H, Akasaka H, Koizumi N, Fujimoto K, Sakano S, Ito R, Kondo T, Kitazawa S, Yamamura H, Takahashi K
    Japanese Journal of Cancer and Chemotherapy 36 3 475 - 478 2009年 [有り][無し]
  • Riko Kitazawa, Kiyoshi Mori, Akira Yamaguchi, Takeshi Kondo, Sohei Kitazawa
    JOURNAL OF CELLULAR BIOCHEMISTRY 105 5 1289 - 1297 2008年12月 [有り][無し]
     研究論文(学術雑誌) 
    The expression of receptor activator of nuclear factor-kappa B ligand (RANKL) is regulated by bone-seeking hormones such as PTH and 1 alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)). Runx2, a master gene for osteoblastic differentiation, also modulates osteoclastogenesis by regulating the RANKL gene. To elucidate the mechanism whereby runx2 and 1,25(OH)(2)D(3) regulate RANKL expression, we studied the function of runx2 on the chromatin structure and on the proximal binding sites using osteoblastic cell lines derived from normal (ST2) and runx2-deficient mice (RD-C6). Although the expression of RANKL in the steady-state was higher in RD-C6 than in ST2, 1,25(OH)(2)D(3)-treatment of the cells increased it 20-fold in ST2 but only 1.8-fold in RD-C6. Transient transfection studies with proximal RANKL 2kb promoter, runx2 knock-down in ST2, and forced expression of runx2 in RD-C6 all confirmed that runx2 set the steady-state expression of the RANKL gene at a low level, but exerted a positive effect on enhanced transcriptional activity in response to 1,25(OH)(2)D(3). Also, assessment of the acetylation status of the area spanning 40 kb upstream of the basic promoter in ST2 and RD-C6 by ChIP assay revealed that whereas H3 and H4 historic acetylation was detected even in the steady-state in RD-C6, it was detected only with 1,25(OH)(2)D(3) in ST2. In the steady-state, runx2 may suppress RANKL gene by condensing the chromatin structure; however, it exerts a positive effect on 1,25(OH)(2)D(3)-induced RANKL transcription when the proximal runx2 sites are accessible. Thus, RANKL expression in stromal/osteoblastic cells is keenly regulated by 1,25(OH)(2)D(3) which transactivates the gene at two different levels. J. Cell. Biochem. 105: 1289-1297, 2008. (c) 2008 Wiley-Liss, Inc.
  • Lin Deng, Tetsuya Adachi, Kikumi Kitayama, Yasuaki Bungyoku, Sohei Kitazawa, Satoshi Ishido, Ikuo Shoji, Hak Hotta
    JOURNAL OF VIROLOGY 82 21 10375 - 10385 2008年11月 [有り][無し]
     研究論文(学術雑誌) 
    We previously reported that cells harboring the hepatitis C virus (HCV) RNA replicon as well as those expressing HCV NS3/4A exhibited increased sensitivity to suboptimal doses of apoptotic stimuli to undergo mitochondrion-mediated apoptosis (Y. Nomura-Takigawa, et al., J. Gen. Virol. 87: 1935-1945, 2006). Little is known, however, about whether or not HCV infection induces apoptosis of the virus-infected cells. In this study, by using the chimeric J6/JFH1 strain of HCV genotype 2a,we demonstrated that HCV infection induced cell death in Huh7.5 cells. The cell death was associated with activation of caspase 3, nuclear translocation of activated caspase 3, and cleavage of DNA repair enzyme poly(ADP-ribose) polymerase, which is known to be an important substrate for activated caspase 3. These results suggest that HCV-induced cell death is, in fact, apoptosis. Moreover, HCV infection activated Bax, a proapoptotic member of the Bcl-2 family, as revealed by its conformational change and its increased accumulation on mitochondrial membranes. Concomitantly, HCV infection induced disruption of mitochondrial transmembrane potential, followed by mitochondrial swelling and release of cytochrome c from mitochondria. HCV infection also caused oxidative stress via increased production of mitochondrial superoxide. On the other hand, HCV infection did not mediate increased expression of glucose-regulated protein 78 (GRP78) or GRP94, which are known as endoplasmic reticulum (ER) stress-induced proteins; this result suggests that ER stress is not primarily involved in HCV-induced apoptosis in our experimental system. Taken together, our present results suggest that HCV infection induces apoptosis of the host cell through a Bax-triggered, mitochondrion-mediated, caspase 3-dependent pathway(s).
  • K. Takeuchi, T. Tsujino, M. Sugimoto, S. Yoshida, S. Kitazawa
    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER 18 6 1285 - 1288 2008年11月 [有り][無し]
     研究論文(学術雑誌) 
    Takeuchi K, Tsujino T, Sugimoto M, Yoshida S, Kitazawa S. Endocervical adenocarcinoma associated with lobular endocervical glandular hyperplasia showing rapid reaccumulation of hydrometra. Int J Gynecol Cancer 2008;18:1285-1288. Mucinous endocervical adenocarcinoma is characterized by increased watery vaginal discharge, but the early diagnosis is sometimes difficult because biopsy specimen might only serve to sample a superficial part of the tumor. The patient presented with complaints of abdominal distention. No vaginal bleeding or watery discharge was observed. Hydrometra was suspected by imaging studies. Rapid reaccumulation of hydrometra was seen despite drainage. Papanicolaou smear of endocervix and endometrium followed by fractional curettage was performed, but failed to confirm the diagnosis. To investigate the unknown origin of hydrometra, an exploratory laparotomy with total hysterectomy and bilateral salpingo-oophorectomy was performed, followed by pelvic lymphadenectomy because biopsy specimens during operation suggested adenocarcinoma of the cervix. The final pathologic study of surgical specimens revealed mucinous adenocarcinoma, which was located on the proximal area of cervix. Adjacent to carcinoma tissue, lobular endocervical glandular hyperplasia (LEGH) was detected. Pyloric gland mucin (HIK1083), MUC6, and MUC5AC were diffusely immunopositive in the cytoplasm of LEGH cells and the immunoreactivity became weaker in adenocarcinoma cells with tumor progression and loss of differentiation. Based on histopathologic features of the present case, there seems to be a possible link between LEGH and conventional mucinous endocervical adenocarcinomas. The physician should keep in mind the possible existence of endocervical adenocarcinoma in a patient showing rapid reaccumulation of hydrometra, when uterine malignancies are clinically suspected and biopsy finding fails to confirm the diagnosis.
  • Junko Ishii, Riko Kitazawa, Kiyoshi Mori, Kevin P. McHugh, Eiichi Morii, Takeshi Kondo, Sohei Kitazawa
    JOURNAL OF CELLULAR BIOCHEMISTRY 105 3 896 - 904 2008年10月 [有り][無し]
     研究論文(学術雑誌) 
    Receptor activator of NF-kappa B (RANK) is a receptor for RANK ligand (RANKL), and signals transduced by RANK-RANKL interaction are prerequisite for the differentiation and activation of osteoclasts. We cloned and characterized a 6-kb fragment containing the 5'-flanking region of the mouse RANK gene. A fragment of 1-kb from the transcription start sites containing four Sp-1 sites and putative binding sites for MITF, CRE/AP-1, and PU.1 was ligated to the pGL3-basic vector, and the promoter activity was confirmed by transfection studies. By electrophoretic gel motility shift assay, both PU.1 and proximal MITF binding site showed specific DNA-protein binding. Co-transfection studies with MITF- and PU.1-expression vectors revealed that MITF and PU.1 increased RANK promoter activity three- and twofold, respectively, and sixfold synergistically. Taken together, these results show that RANK transcription is positively regulated by both PU.1 and MITF. The effect of lipopolysaccharide (LPS) on RANK gene expression, analyzed by in situ hybridization using mouse bone tissue, showed that LPS decreased RANK transcripts of both precursor and mature osteoclasts. Furthermore, LPS treatment of RAW.264.7 cells decreased their RANK mRNA expression by 70%, mirroring the decrease of PU.1 and MITF mRNA. Short-term treatment with LPS decreased the promoter activity of pGL3-WT by 70%. Although LPS has been reported to promote osteoclastogenesis in chronic and local pyogenic inflammation, we speculate that LPS per se may directly suppress RANK expression in the osteoclastic cell lineage by down-regulating the expression of PU.1 and MITF genes in acute and systemic severe endotoxemia, such as in septic shock. J. Cell. Biochem. 105: 896-904, 2008. (C) 2008 Wiley-Liss, Inc.
  • Masanori Fuse, Norihide Yokoi, Masami Shinohara, Taku Masuyama, Riko Kitazawa, Sohei Kitazawa, Susumu Seino
    PHYSIOLOGICAL GENOMICS 35 1 96 - 105 2008年09月 [有り][無し]
     研究論文(学術雑誌) 
    Fuse M, Yokoi N, Shinohara M, Masuyama T, Kitazawa R, Kitazawa S, Seino S. Identification of a major locus for islet inflammation and fibrosis in the spontaneously diabetic Torii rat. Physiol Genomics 35: 96-105, 2008. First published July 8, 2008; doi: 10.1152/physiolgenomics.90214.2008.-The pathogenesis of inflammation and fibrosis in the pancreatic islets in diabetes is largely unknown. Spontaneously diabetic Torii (SDT) rats exhibit inflammation and fibrosis in and around the islets during the development of the disease. We investigated genetic factors for diabetes, islet inflammation, and fibrosis in the SDT rat. We produced F1 and F2 rats by intercross between SDT and F344 rats, examined the onset of diabetes, glucose tolerance, and histology of the pancreas, and performed genetic analysis of these traits. We then established a congenic strain carrying the SDT allele at the strongest diabetogenic locus on the F344 genetic background and characterized glucose tolerance and histology of the pancreas. F1 rats showed glucose intolerance and inflammatory changes mainly in the islets. Genetic analysis of diabetes identified a major locus on chromosome 3, designated Dmsdt1, at which a dominantly acting SDT allele was involved. Quantitative trait locus (QTL) analysis of glucose tolerance revealed, in addition to Dmsdt1 [logarithm of odds (LOD) 5.3 near D3Mit12], three other loci, designated Dmsdt2 (LOD 4.2 at D8Rat46), Dmsdt3 (LOD 3.8 near D13Arb5), and Dmsdt4 (LOD 5.8 at D14Arb18). Analysis of a congenic strain for Dmsdt1 indicates that the dominantly acting SDT allele induces islet inflammation and fibrosis. Thus we have found a major locus on chromosome 3 for islet inflammation and fibrosis in the SDT rat. Identification of the genes responsible should provide insight into the pathogenesis of diabetes.
  • Takeshi Kondo, Riko Kitazawa, Sohei Kitazawa
    DIGESTIVE DISEASES AND SCIENCES 53 8 2287 - 2289 2008年08月 [有り][無し]
     研究論文(学術雑誌) 
    An invasive micropapillary carcinoma ( IMPC) is defined as a carcinoma composed of small clusters of tumor cells lying within clear spaces simulating vascular channels [ 1]. It is a histological variant of invasive breast carcinoma with poor clinical prognosis [2, 3]. This distinct histological pattern has been described in various organs, including the urinary bladder, lung, ovary, and major salivary glands [4 - 8]. Although rarely observed as a pure histological component, IMPC is usually mixed with otherwise conventional carcinoma [3] and is therefore often referred to as carcinoma with a micropapillary component. In cases of adenocarcinoma with a micropapillary component, an abrupt transition is usually seen between the invasive micropapillary component and conventional adenocarcinoma [3]. IMPCs are all invariably associated with high aggressiveness, extensive lymphovascular invasion, extensive lymph node metastases, and poor prognosis [1-3]. We describe the first case of primary IMPC originating in the stomach as a histologic subcomponent of recurrent gastric adenocarcinoma.
  • Naonobu Nishino, Yoshikazu Tamori, Sanshiro Tateya, Takayuki Kawaguchi, Tetsuro Shibakusa, Wataru Mizunoya, Kazuo Inoue, Riko Kitazawa, Sohei Kitazawa, Yasushi Matsuki, Ryuji Hiramatsu, Satoru Masubuchi, Asako Omachi, Kazuhiro Kimura, Masayuki Saito, Taku Amo, Shigeo Ohta, Tomohiro Yamaguchi, Takashi Osumi, Jinglei Cheng, Toyoshi Fujimoto, Harumi Nakao, Kazuki Nakao, Atsu Aiba, Hitoshi Okamura, Tohru Fushiki, Masato Kasuga
    JOURNAL OF CLINICAL INVESTIGATION 118 8 2808 - 2821 2008年08月 [有り][無し]
     研究論文(学術雑誌) 
    White adipocytes are unique in that they contain large unilocular lipid droplets that occupy most of the cytoplasm. To identify genes involved in the maintenance of mature adipocytes, we expressed dominant-negative PPAR gamma in 3T3-L1 cells and performed a microarray screen. The fat-specific protein of 27 kDa (FSP27) was strongly downregulated in this context. FSP27 expression correlated with induction of differentiation in cultured preadipocytes, and the protein localized to lipid droplets in murine white adipocytes in vivo. Ablation of FSP27 in mice resulted in the formation of multilocular lipid droplets in these cells. Furthermore, FSP27-deficient mice were protected from diet-induced obesity and insulin resistance and displayed an increased metabolic rate due to increased mitochondrial biogenesis in white adipose tissue (WAT). Depletion of FSP27 by siRNA in murine cultured white adipocytes resulted in the formation of numerous small lipid droplets, increased lipolysis, and decreased triacylglycerol storage, while expression of FSP27 in COS cells promoted the formation of large lipid droplets. Our results suggest that FSP27 contributes to efficient energy storage in WAT by promoting the formation of unilocular lipid droplets, thereby restricting lipolysis. In addition, we found that the nature of lipid accumulation in WAT appears to be associated with maintenance of energy balance and insulin sensitivity.
  • Yutaka Takahashi, Keiji Iida, Ryoko Takeno, Riko Kitazawa, Sohei Kitazawa, Hidetsuna Kitamura, Yoshio Fujioka, Hiroyuki Yamada, Fumio Kanda, Shigeo Ohta, Kiyomi Nishimaki, Masayo Fujimoto, Takeshi Kondo, Genzo Iguchi, Kentaro Takahashi, Hidesuke Kaji, Yasuhiko Okimura, Kazuo Chihara
    ENDOCRINE JOURNAL 55 3 509 - 514 2008年06月 [有り][無し]
     研究論文(学術雑誌) 
    Mitochondrial diabetes is characterized by diabetes and hearing loss in maternal transmission with a heteroplasmic A3243G mutation in the mitochondrial gene. In patients with the mutation, it has been reported that hepatic involvement is rarely observed. We demonstrated a case of hypertrophic cardiomyopathy and hepatic failure with mitochondrial diabetes. To clarify the pathogenesis we analyzed the mitochondrial ultrastructure in the myocytes, the reactive oxygen species (ROS) production in the liver and the status of lieteroplasmy of the mitochondrial A3243G mutation in the organs involved. In cardiomyocytes and skeletal muscle, electron microscopic analysis demonstrated typical morphological mitochondrial abnormalities. Immunohistochemical analysis demonstrated enhanced ROS production associated with marked steatosis in the liver, which is often associated with mitochondrial dysfunction. Analysis of the A3243G mutation revealed a substantial ratio of heteroplasmy in these organs including the liver. The presence of steatosis and enhanced oxidative stress in the liver suggested that hepatic failure was associated with mitochondrial dysfunction.
  • Kaoru Funaki, Katsuhiro Sawada, Hidenobu Fukunishi, Riko Kitazawa, Sohei Kitazawa
    INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS 100 3 282 - 283 2008年03月 [有り][無し]
  • Jeroen de Jong, Hans Stoop, Ad J. M. Gillis, Remko Hersmus, Ruud J. H. L. M. van Gurp, Gert-Jan M. van de Geijn, Ellen van Drunen, H. Berna Beverloo, Dorninik T. Schneider, Jon K. Sherlock, John Baeten, Sohei Kitazawa, E. Joop van Zoelen, Kees van Roozendaal, J. Wolter Oosterhuis, Leendert H. J. Looijenga
    GENES CHROMOSOMES & CANCER 47 3 185 - 196 2008年03月 [有り][無し]
     研究論文(学術雑誌) 
    Testicular germ cell tumors of adolescents and adults (TGCTs) can be classified into seminomatous and nonseminomatous tumors. Various nonseminomatous cell lines, predominantly embryonal carcinoma, have been established and proven to be valuable for pathobiological and clinical studies. So far, no cell lines have been derived from seminoma which constitutes more than 50% of invasive TGCTs. Such a cell line is essential for experimental investigation of biological characteristics of the cell of origin of TGCTs, i.e., carcinoma in situ of the testis, which shows characteristics of a seminoma cell. Before a cell line can be used as model, it must be verified regarding its origin and characteristics. Therefore, a multidisciplinary approach was undertaken on TCam-2 cells, supposedly the first seminoma cell line. Fluorescence in situ hybridization, array comparative genomic hybridization, and spectral karyotyping demonstrated an aneuploid DNA content, with gain of 12p, characteristic for TGCTs. Genome wide mRNA and microRNA expression profiling supported the seminoma origin, in line with the biallelic expression of imprinted genes IGF2/H19 and associated clemethylation of the imprinting control region. Moreover, the presence of specific markers, demonstrated by immunohistochemistry, including (wild type) KIT, stem cell factor, placental alkaline phosphatase, OCT3/4 (also demonstrated by a specific Q-PCR) and NANOG, and the absence of CD30, SSX2-4, and SOX2, confirms that TCam-2 is a seminoma cell line. Although mutations in oncogenes and tumor suppressor genes are rather rare in TGCTs, TCam-2 had a mutated BRAF gene (V600E), which likely explains the fact that these cells could be propagated in vitro. In conclusion, TCam-2 is the first well-characterized seminoma-derived cell line, with an exceptional mutation, rarely found in TGCTs. (c) 2007 Wiley-Liss, Inc.
  • Michiko Takahashi, Yutaka Takahashi, Kenichi Takahashi, Fyodor N. Zolotaryov, Kyoung Su Hong, Riko Kitazawa, Keiji Iida, Yasuhiko Okimura, Hidesuke Kaji, Sohei Kitazawa, Masato Kasuga, Kazuo Chihara
    FEBS LETTERS 582 5 573 - 578 2008年03月 [有り][無し]
     研究論文(学術雑誌) 
    To explore a novel adipokine, we screened adipocyte differentiation-related gene and found that TIG2/chemerin was strongly induced during the adipocyte differentiation. Chemerin was secreted by the mature 3T3-L1 adipocytes and expressed abundantly in adipose tissue in vivo as recently described. Intriguingly, the expression of chemerin was differently regulated in the liver and adipose tissue in db/db mice. In addition, serum chemerin concentration was decreased in db/db mice. Chemerin and its receptor/ChemR23 were expressed in mature adipocytes, suggesting its function in autocrine/paracrine fashion. Finally, chemerin potentiated insulin-stimulated glucose uptake concomitant with enhanced insulin signaling in the 3T3-L1 adipocytes. These data establish that chemerin is a novel adipokine that regulates adipocyte function. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
  • D. Eckert, D. Nettersheim, L. C. Heukamp, S. Kitazawa, K. Biermann, H. Schorle
    CELL AND TISSUE RESEARCH 331 2 529 - 538 2008年02月 [有り][無し]
     研究論文(学術雑誌) 
    Of all malignancies diagnosed in men between 17 and 45 years of age, 60% are germ cell tumors (GCT). GCT arise from carcinoma in situ cells, which are thought to originate from a transformed fetal germ cell, the gonocyte. Seminoma together with embryonal carcinoma represent the most frequent subtypes of GCT. However, the nature of the molecular pathways involved in seminoma formation remains elusive. Therefore, analysis of appropriate cell culture systems is an important prerequisite for further understanding of the etiology of this tumor entity. Although several cell lines for embryonal carcinoma have been established and analyzed, so far only two cell lines from seminoma patients have been reported. In the present study, we have analyzed these seminoma cell lines (TCam-2 and JKT-1) and compared the gene-expression profiles with those of normal tissue and of seminoma and embryonal carcinoma by using DNA Array technology. We have found that TCam-2 clusters with the group of classical seminoma, whereas JKT-1 clusters with the group of embryonal carcinoma. Using reverse transcription/polymerase chain reaction, Western blot, and immunohistochemistry, we have confirmed the seminoma-like nature of TCam-2, whereas JKT-1 lacks expression for most of the genes detectable in GCTs, thus making doubtful the germ cell nature of this cell line. The data represent the first genome-wide expression analysis of the two cell lines and comparison/clustering with subgroups of germ cell tumors. Only TCam-2 seems to represent a suitable in vitro model for seminoma.
  • Establishment of 14 wheat lines carrying telosomes of barley chromosome 7H
    Nishino N, Tamori Y, Tateya S, Kawaguchi T, Shibakusa T, Mizunoya W, Inoue K, Kitazawa R, Kitazawa S, Matsuki Y, Hiramatsu R, Masubuchi S, Omachi A, Kimura K, Saito M, Amo T, Ohta S, Yamaguchi T, Osumi T, Cheng J, Fujimoto T, Nakao H, Nakao K, Aiba A, Okamura H, Fushiki T, Kasuga M
    J Clin Invest. 2008 Aug;118(8):2808-21. 2008年 [有り][無し]
  • Higo S, Miyata S, Qing Y.J, Kitazawa R, Kitazawa S, Kasuga M
    Kobe Journal of Medical Sciences 54 1 35 - 45 2008年 [有り][無し]
  • Agus Darwanto, Riko Kitazawa, Kiyoshi Mori, Takeshi Kondo, Sohei Kitazawa
    ACTA HISTOCHEMICA ET CYTOCHEMICA 41 5 135 - 142 2008年 [有り][無し]
     研究論文(学術雑誌) 
    Hypermethylation-dependent silencing of the gene is achieved by recruiting methyl-CpG binding proteins ( MeCPs). Among the MeCPs, MeCP2 is the most abundantly and ubiquitously expressed in various types of cells. We first screened the distribution and expression pattern of MeCP2 in adult and developing rat tissues and found strong MeCP2 expression, albeit rather ubiquitously among normal tissues, in ganglion cells and intestinal epithelium in the small intestine, in Purkinje cells and neurons in the brain, in spermatogonia and in epithelial cells in the epididymal duct of the testis. We then assessed the expression and the methylation pattern of the promoter region of cyclin D1 by immunohistochemistry and sodium bisulfite mapping, and found that cyclin D1 expression in the epididymal duct decreased rapidly during rat development: strong in newborn rats and very weak or almost negative in 7-day-old rats. Mirroring the decrease of cyclin D1 expression, methylated cytosine at both CpG and non-CpG loci in the cyclin D1 promoter was frequently observed in the epididymal duct of 7-day-old rats but not in that of newborn rats. Interestingly, MeCP2 expression also increased concomitant with the increase of methylation. Cyclin D1 expression in the epididymal duct may be efficiently regulated by the epigenetic mechanism of the cooperative increase of MeCP2 expression and promoter methylation.
  • Sopaporn Niemhom, Sohei Kitazawa, Riko Kitazawa, Sakan Maeda, Juvady Leopairat
    CANCER DETECTION AND PREVENTION 32 2 127 - 134 2008年 [有り][無し]
     研究論文(学術雑誌) 
    Background: Epstein-Barr virus (EBV) is documented as the important etiologic agent of nasopharyngeal carcinoma (NPC) but the mechanism of development and pathogenesis induced by EBV is presently unclear. Hypermethylation of epithelial-cadherin (E-cadherin) promoter has been shown to be induced in NPC cell line by EBV LMP1 via DNA methyltransferase activation. EBV genomes and hypermethylation of E-cadherin promoter were investigated in NPC tissues to evaluate the role of EBV in the hypermethylation and pathogenesis of NPC. Methods: Methylation-specific polymerase chain reaction (MSP) was performed to detect E-cadherin promoter hypermethylation in paraffin embedded tissues from patients with NPC and normal nasopharyngeal tissues. EBV genomes were detected by PCR in the tissue samples. Results: Hypermethylation of E-cadherin promoter and EBV were predominantly detected in undifferentiated and non-keratinizing NPC compared to those in squamous cell NPC. Hypermethylation of E-cadherin was found in 28 of 38 (73.7%) patient samples. EBV was detected in 22 of the 28 (78.6%) NPC samples demonstrating E-cadherin hypermethylation. EBV genomes and hypermethylation were not detected in normal nasopharyngeal tissues. Significant association was found between E-cadherin hypermethylation and EBV genomes (p < 0.001; Fisher's exact test). Hypermethylation of E-cadherin was more frequently detected in advanced stages compared to those in early stages of NPC (p = 0.036; Fisher's exact test). Conclusions: The high incidence of EBV with the consistency of E-cadherin hypermethylation, particularly in undifferentiated and non-keratinizing NPC suggests the role of EBV in the hypermethylation. EBV exists at early stage of NPC that induces the hypermethylation and contributes to progression of the disease to the advanced stage of NPC. (C) 2008 International Society for Preventive Oncology. Published by Elsevier Ltd. All rights reserved.
  • Takeshi Kondo, Riko Kitazawa, Akira Yamaguchi, Sohei Kitazawa
    JOURNAL OF CELLULAR BIOCHEMISTRY 103 1 335 - 345 2008年01月 [有り][無し]
     研究論文(学術雑誌) 
    Increased bone fragility attributed to osteopenia is a serious side effect of glucocorticoid treatment. Glucocorticoid-induced bone loss is caused primarily by hypofunction and apoptosis of osteoblasts, and secondarily by accelerated bone resorption. To explore the mechanism whereby dexamethasone (Dex) stimulates osteoclastogenesis in the coculture system, we analyzed the effect of Dex on the expression of both mouse osteoprotegerin (OPG) and receptor activator of NF-kappa B ligand (RANKL). Dex reduced OPG transcripts and OPG protein secretion by the ST2 osteoblastic cells. Since mainly the c-Jun homodimer maintains the steady-state transcription of the OPG gene, we examined the effect of Dex on c-Jun signaling in ST2 cells. Western blotting disclosed that Dex decreased the amount of phospho-c-Jun protein (p-c-Jun) and, correspondingly, the amount of the phosphorylated p46 isoform of Jun N-terminal kinase (JNK). The amount of phospho-SEK1 also decreased after Dex treatment, while the amounts of phospho-ERK and p38 remained constant. Among mitogen-activated protein (MAP) kinase inhibitors, the JNK inhibitor mimicked the inhibitory effect of Dex on OPG promoter activity. On the other hand, Dex treatment per se showed a nominal increase of RANKL gene expression. A part of Dex-mediated OPG gene suppression was achieved by the suppression of beta-catenin signaling. We speculate therefore that the bone resorptive action of Dex is mediated mainly by the inhibition of OPG by transrepressing the OPG gene through the AP-1 site, with a reduction (mediated mainly by the decrease in the p46 isoform of JNK) in the proportion of p-c-Jun in a JNK-dependent manner.
  • A. McIntyre, B. Summersgill, Y. J. Lu, E. Missiaglia, S. Kitazawa, J. W. Oosterhuis, L. H. Looijenga, J. Shipley
    BRITISH JOURNAL OF CANCER 97 12 1707 - 1712 2007年12月 [有り][無し]
     研究論文(学術雑誌) 
    Testicular germ cell tumours of adults and adolescents (TGCT) include seminomas (SE) and nonseminomas (NS), with spermatocytic seminomas (SSE) representing a distinct entity in older men. SE and NS have gain of 12p material in all cases, whereas SSE are associated with overrepresentation of chromosome 9. Here, we compare at the chromosomal level, copy number imbalances with global expression changes, identified by comparative expressed sequence hybridisation analyses, in seven SE, one combined tumour, seven NS and seven cell lines. Positive correlations were found consistent with copy number as a main driver of expression change, despite reported differences in methylation status in SE and NS. Analysis of chromosomal copy number and expression data could not distinguish between SE and NS, in-keeping with a similar genetic pathogenesis. However, increased expression from 4q22, 5q23.2 and 9p21 distinguished SSE from SE and NS and decreased copy number and expression from 2q36-q37 and 6q24 was a specific feature of NS-derived cell lines. Our analysis also highlights 19 regions with both copy number and expression imbalances in greater than 40% of cases. Mining available expression array data identified genes from these regions as candidates for involvement in TGCT development.
  • Ping Wei, Takaya Satoh, Hironori Edamatsu, Atsu Aiba, Tomiyoshi Setsu, Toshio Terashima, Sohei Kitazawa, Kazuki Nakao, Yoko Yoshikawa, Masako Tamada, Tohru Kataoka
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 363 1 106 - 112 2007年11月 [有り][無し]
     研究論文(学術雑誌) 
    A multitude of guanine nucleotide exchange factors (GEFs) regulate Rap1 small GTPases, however, their individual functions remain obscure. Here, we investigate the in vivo function of the Rap1 GEF RA-GEF-1. The expression of RA-GEF-1 in wild-type mice starts at embryonic day (E) 8.5, and continues thereafter. RA-GEF-1(-/-) mice appear normal until E7.5, but become grossly abnormal and dead by E9.5. This mid-gestation death appears to be closely associated with severe defects in yolk sac blood vessel formation. RA-GEF-1(-/-) yolk sacs form apparently normal blood islands by E8.5, but the blood islands fail to coalesce into a primary vascular plexus, indicating that vasculogenesis is impaired. Furthermore, RA-GEF-1(-/-) embryos proper show severe defects in the formation of major blood vessels. These results suggest that deficient Rap1 signaling may lead to defective vascular morphogenesis in the yolk sac and embryos proper. (C) 2007 Elsevier Inc. All rights reserved.
  • N. C. Goddard, A. McIntyre, B. Summersgill, D. Gilbert, S. Kitazawa, J. Shipley
    INTERNATIONAL JOURNAL OF ANDROLOGY 30 4 337 - 348 2007年08月 [有り][無し]
     研究論文(学術雑誌) 
    Testicular germ cell tumours (TGCTs) are the leading cause of cancer deaths in young male Caucasians. Identifying changes in DNA copy number can pinpoint genes involved in tumour development. We defined the smallest overlapping regions of imbalance in TGCTs using array comparative genomic hybridization analysis. Novel regions, or regions which refined those previously reported, were identified. The expression profile of genes from 12p, which is invariably gained in TGCTs, and amplicons defined at 12p11.2-12.1 and 4q12, suggest KRAS and KIT involvement in TGCT and seminoma development, respectively. Amplification of these genes was not found in intratubular germ cell neoplasia adjacent to invasive disease showing these changes, suggesting their involvement in tumour progression. Activating mutations of RAS genes (KRAS or NRAS) and overexpression of KRAS were mutually exclusive events. These, correlations between the expression levels of KIT, KRAS and GRB7 (which encodes an adapter molecule known to interact with the KIT tyrosine kinase receptor) and other reported evidence reviewed here, are consistent with a role for activation of KIT and RAS signalling in TGCT development. In order to assess a role for KIT in seminomas, we modulated the level of KIT expression in TCam-2, a seminoma cell line. The likely seminomatous origin of this cell line was supported by demonstrating KIT and OCT3/4 overexpression and gain of 12p material. Reducing the expression of KIT in TCam-2 through RNA inhibition resulted in decreased cell viability. Further understanding of KIT and RAS signalling in TGCTs may lead to novel therapeutic approaches for these tumours.
  • C. Wylie, J. Shipley, R. T. D. Oliver, J. W. Oosterhuis, E. Rajpert-De Meyts
    INTERNATIONAL JOURNAL OF ANDROLOGY 30 4 349 - 349 2007年08月 [有り][無し]
  • Yasuhiro Hamada, Satoshi Miyata, Tomoko Nii-Kono, Riko Kitazawa, Sohei Kitazawa, Satomi Higo, Michiru Fukunaga, Shigemitu Ueyama, Hajime Nakamura, Junji Yodoi, Masafumi Fukagawa, Masato Kasuga
    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 22 6 1547 - 57 2007年06月 [有り][無し]
     
    BACKGROUND: Oxidative stress has been suggested to play an important role in the pathogenesis of diabetic nephropathy. In the present study, the effects of thioredoxin1 (TRX1) overexpression, a small protein with antioxidant property, on the development of diabetic nephropathy in streptozotocin-induced diabetic animals were investigated using TRX1 transgenic mice (TRX1-Tg). METHODS: Eight-week-old male TRX1-Tg and wild-type mice littermates (WT) mice were treated either with streptozotocin (200 mg/kg) or vehicle alone. After 24 weeks of treatment, diabetic nephropathy and oxidative stress were assessed in these four groups of mice, by biochemical analyses of blood and urine, as well as by histological analyses of the kidneys. RESULTS: Haemoglobin A1c (HbA1c) levels of diabetic TRX1-Tg were not significantly different from those of the diabetic WT. Nevertheless, an augmented urinary albumin excretion observed in diabetic WT was significantly diminished in diabetic TRX1-Tg. Histological study revealed that pathological changes such as mesangial matrix expansion and tubular injury were significantly prevented in diabetic TRX1-Tg accompanied by a reduced tendency of expression of transforming growth factor-beta as compared with diabetic WT. In parallel, urinary excretion of 8-hydroxy-2'-deoxyguanosine and acrolein adduct and the immunostaining intensities of these markers in the kidney were significantly higher in diabetic WT compared with non-diabetic mice. The markers were significantly suppressed in diabetic TRX1-Tg, an indication of systemic and renal oxidative stress attenuation by TRX1 overexpression. CONCLUSION: These findings indicated the significant role of oxidative stress in the development of diabetic nephropathy and a potential inhibition of progression of nephropathy by TRX1.
  • H. Fukunishi, K. Funaki, K. Ikuma, Y. Kaji, K. Sugimura, R. Kitazawa, S. Kitazawa
    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER 17 3 724 - 728 2007年05月 [有り][無し]
     研究論文(学術雑誌) 
    Uterine leiomyosarcoma, initially diagnosed as leiomyoma on magnetic resonance (MR) images, was disclosed after focused ultrasound surgery (FUS). The tumor did not display high signal intensity on either T1- or T2-weighted images on the patient's first visit. Four months thereafter, T2-weighted images revealed a high signal intensity area within the tumor, while T1-weighted images showed low signal intensity. Six months after FUS, the nonperfused volume calculated on meglumine gadoterate-enhanced T1-weighted images decreased markedly and an intermediate signal intensity in a circular area on T2-weighted images appeared to be atypically increasing in volume. After laparoscopic myomectomy, this tumor was diagnosed as uterine leiomyosarcoma coexistent with leiomyoma. The early stages of uterine leiomyosarcoma are clinically difficult to diagnose; therefore, both careful monitoring during FUS and close follow-up after the procedure are vital.
  • Yasuhiro Hamada, Sohei Kitazawa, Riko Kitazawa, Hideki Fujii, Masato Kasuga, Masafumi Fukagawa
    BONE 40 5 1408 - 1414 2007年05月 [有り][無し]
     研究論文(学術雑誌) 
    Diabetic osteopenia causes an increase in bone fracture and a delay in healing of fractures, and affects the quality of life. However, the mechanisms responsible for the disease have not been clearly identified. Oxidative stress may be a potential candidate for the pathogenesis, since it is increased under diabetic conditions and is known to induce cellular dysfunction in a wide variety of cell types. Although in vitro studies have shown that oxidative stress inhibits osteoblastic differentiation and induces osteoblast insults and apoptosis, the relationship between diabetic osteopenia and oxidative stress remains unclear. To explore these issues, analysis of a mouse model that represents the diabetic osteopenia as seen in patients with diabetes is necessary. However, there are few reports of such a model. Therefore, we focused on the streptozotocin (STZ)-induced diabetic mouse, one of the most common animal models of type I diabetes. Eight-week-old male C57BL/6 mice were randomly assigned to the following three groups: 1) control group, 2) diabetic group, and 3) insulin-treated diabetic group. After 12 weeks of STZ treatment, the physical properties of the femora, and the static and dynamic parameters of bone histomorphometry of the tibiae from STZ-induced diabetic mice (STZ-mice) were assessed, and oxidative stress in the whole body and bone of the mice was evaluated. Renal function was comparable in all three groups at the end of the experimental period. In addition, no significant difference in serum PTH, Ca, and P was found among the three groups. In contrast, radiological analysis demonstrated a significant decrease in trabecular bone volume, and histomorphometric analyses confirmed that parameters for both bone formation (OV/BV, OS/BS, and BFR/BS) and bone resorption (ES/BS and Oc.S/BS) were also significantly lower in STZ-mice. In addition, urinary excretion of 8-hydroxydeoxyguano sine, a marker of oxidative DNA damage, was elevated in STZ-mice. Further immunohistological studies showed intensified immunostaining of an oxidative stress marker in bone tissue including the osteoblasts of diabetic mice. Here, we demonstrated that STZ-mice exhibit low-turnover osteopenia associated with increased oxidative stress. (c) 2006 Elsevier Inc. All rights reserved.
  • Yutaka Takahashi, Keiji Iida, Kentaro Takahashi, Shiro Yoshioka, Hidenori Fukuoka, Ryoko Takeno, Mari Imanaka, Hitoshi Nishizawa, Michiko Takahashi, Yasushi Seo, Yoshitake Hayashi, Takuma Kondo, Yasuhiko Okimura, Hidesuke Kaji, Riko Kitazawa, Sohei Kitazawa, Kazuo Chihara
    GASTROENTEROLOGY 132 3 938 - 943 2007年03月 [有り][無し]
     研究論文(学術雑誌) 
    Background & Aims: Nonalcoholic steatohepatitis (NASH) is an emerging progressive hepatic disease and demonstrates steatosis, inflammation, and fibrosis. Insulin resistance is a common feature in the development of NASH. Molecular pathogenesis of NASH consists of 2 steps: triglyceride accumulation in hepatocytes with insulin resistance and an enhanced oxidative stress caused by reactive oxygen species. Interestingly, NASH demonstrates a striking similarity to the pathologic conditions observed in adult growth hormone deficiency (AGHD). AGHD is characterized by decreased lean body mass, increased visceral adiposity, abnormal lipid profile, and insulin resistance. Moreover, liver dysfunctions with hyperlipidemia and nonalcoholic fatty liver disease (NAFLD) are frequently observed in patients with AGHD, and it is accompanied by metabolic syndrome. Methods: We studied a case diagnosed as NASH with hyperlipidemia in AGHD. The effect of GH-replacement therapy on the patient was analyzed. Results: Six months of GH-replacement therapy in the patient drastically ameliorated NASH and the abnormal lipid profile concomitant with a marked reduction in oxidative stress. Conclusions: These results suggest that GH plays an essential role in the metabolic and redox regulation in the liver.
  • Kitazawa R, Kitazawa S
    Molecular Endocrinology 21 1 148 - 158 2007年01月 [有り][無し]
     研究論文(学術雑誌) 
    Receptor activator of nuclear factor-kappa B ligand (RANKL) expression is tissue specific and limited to certain subsets of T-lymphocytes and stromal/osteoblastic cells. Even among osteoblasts, RANKL is expressed on about 20% of osteoblasts of the normal mouse. To clarify the mechanism of population-specific RANKL expression, we analyzed the effect of CpG methylation on its transcription, mRNA and protein expression as well as on osteoclastogenesis. Subpopulations of ST2 cells were used: P9, which expresses RANKL and supports osteoclastogenesis, and P16, which does not. By sodium bisulfite mapping, the rate of CpG methylation of the -65/+350 region, especially of CpG locus no. 1 three bases upstream of the TATA-box, was higher in P16 than in P9 ST2 cells. ChIP and gel shift assay showed that methylated CpG locus no. 1 was a target of MeCP2 binding that, in turn, blocked the binding of the TATA-box binding protein to the TATA-box. In vitro methylation by SssI of the promoter construct reduced its transcriptional activity at the steady state and its response to 1 alpha,25(OH)(2) vitamin D-3. Conversely, treatment with DNA methylase inhibitor, 5-aza-2'-deoxycytidine, significantly restored RANKL expression and osteoclastogenesis in P16 cells. Except for primary cultured osteoblasts, CpG locus no. 1 was frequently methylated in various normal mouse tissues. We propose that the methylation status of the CpG locus three bases upstream of the TATA-box modulates the control of cell- and tissue-specific expression of RANKL gene and osteoclastogenesis. The heterogeneity of stromal/osteoblastic cells in response to bone-resorbing stimuli may be attributed, in part, to the methylation status of the RANKL gene promoter.
  • Sohei Kitazawa, Atsushi Takenaka, Takeshi Kondo, Akira Mizoguchi, Riko Kitazawa
    HISTOCHEMISTRY AND CELL BIOLOGY 126 6 665 - 677 2006年12月 [有り][無し]
     研究論文(学術雑誌) 
    We established a monoclonal antibody (MAb), 5G9, with the use of a fixed seminoma tissue from an archival paraffin-embedded specimen, as an immunogen. Without antigen retrieval, positive 5G9-immunohistochemical staining was confined mostly to primordial germ cells, spermatogonia and various germ cell tumors. 5G9 recognized a mitochondrial 32-kD protein with an isoelectric point of pH 4.2, identified as a multifunctional ubiquitous protein, receptor for globular head of C1q (gC1qR), whose epitope was mapped in a disordered loop connecting the beta 3 and the beta 4 strands. Reflecting the ubiquitous distribution of gC1qR, with antigen retrieval, 5G9 was found reactive to a wide range of normal and tumor tissues. Since several co-precipitated and phosphorylated bands were observed in various human cell lines but not in germ cell tumor cell lines by in vitro phosphorylation assay, we speculate that the epitope of gC1qR is specifically unmasked in the germ cell lineage. By reducing gC1qR by siRNA, a significant increase was observed in the number of apoptotic cells in ITO-II and TCam-2 cell lines, but to a lesser extent in the Colo201 colon cancer cell line, showing an antiapoptotic property of gC1qR in the germ cells. Since protein-protein interaction is partially preserved by fixation, archival paraffin-embedded specimens can be a valuable source of immunogens for generating monoclonal antibodies (MAbs) that recognize tissue-specific protein conformation.
  • Kyousuke Takeuchi, Hisashi Tateiwa, Shinya Hamana, Shigeki Yoshida, Sohei Kitazawa, Takeshi Maruo
    ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA 85 9 1146 - 1147 2006年09月 [有り][無し]
     研究論文(学術雑誌)
  • Takeshi Kondo, Riko Kitazawa, Naoko Noda-Maeda, Sohei Kitazawa
    PATHOLOGY INTERNATIONAL 56 9 554 - 557 2006年09月 [有り][無し]
     研究論文(学術雑誌) 
    A 36-year-old woman presenting with fetal growth restriction in the 25th week of gestation was referred to Kobe University Hospital where hydrops fetalis was detected. A stillborn fetus, 2012 g in weight and 40 cm in height, was delivered in the 33rd week of gestation. The mother had no past history of non-steroidal anti-inflammatory drug (NSAID) use during the pregnancy. The male fetus showed maceration without macroscopic anomalies, but it was markedly edematous with bilateral pleural effusion and massive ascites. The autopsy revealed an enlarged heart and aortic coarctation in the region of the ductus arteriosus. A mild form of aortic coarctation and premature closure of the ductus arteriosus with fibrous thickening of the wall were observed. The lungs were atelectatic with vascular dilatation and congestion. This is the first documented case of hydrops fetalis caused by spontaneous premature closure of the ductus arteriosus concomitant with aortic coarctation. The findings suggest that some form of idiopathic, or spontaneous, closure of the ductus arteriosus can be one of the causes of chronic fetal heart failure, coarctation of the aorta, and fetal hydrops.
  • Kiyoshi Mori, Riko Kitazawa, Takeshi Kondo, Sakan Maeda, Akira Yamaguchi, Sohei Kitazawa
    JOURNAL OF CELLULAR BIOCHEMISTRY 98 6 1629 - 1644 2006年08月 [有り][無し]
     研究論文(学術雑誌) 
    Runx2 regulates the target genes characteristic of osteoblastic phenotypes, while exerting diverse and sometimes controversial effects on osteoblastic cells depending on their differentiation stage. Receptor activator of nuclear factor-KB (RANK) ligand (RANKL) is a membrane bound cytokine essential for osteo(chondro)clastogenesis. During endochondral ossification, while Runx2-positive hypertrophic chondrocytes express RANKL, the steady-state expression of the RANKL gene in osteoblastic cells is, at later stages, kept at a relatively low level to sustain the established bone. The aim of this study was to elucidate the mechanism whereby Runx2 and the protein kinase A (PKA) pathway modulate RANKL expression, especially from the viewpoint of their functions in RANKL basic promoter activity and in chromatin structural changes in osteoblastic/stromal cells. Osteoblastic/stromal cell lines derived from normal and Runx2-deficient mice were used to analyze endogenous RANKL gene expression by real-time reverse transcription (RT)-PCR, the acetylation status of the H3 and H4 histone proteins associated with the 5'-flanking region of the RANKL gene by chromatin immunoprecipitation, and the exogenously transfected RANKL gene promoter activity both in the steady-state and under PKA-activated conditions. Here, we demonstrate that Runx2 suppresses steady-state RANKL gene expression by condensing chromatin, while showing a slightly positive effect on RANKL basic promoter activity. Besides acting through the CRE-like region (-0.96 kb) of the RANKL gene promoter, forskolin (FK) treatment transactivates the RANKL gene by antagonizing the function of Runx2, by reducing Runx2 mRNA expression and by opening the chromatin conformation far upstream (more than 40 kb) of the RANKL gene.
  • Riko Kitazawa, Sohei Kitazawa, Yoshihiro Nishimura, Takeshi Kondo, Chiho Obayashi
    PATHOLOGY INTERNATIONAL 56 8 449 - 452 2006年08月 [有り][無し]
     研究論文(学術雑誌) 
    Pulmonary carcinosarcoma, consisting of both carcinoma and sarcoma with a heterologous element, is a rare subtype, comprising approximately 0.3% of primary lung neoplasia. A 57-year-old man was admitted because of severe dyspnea. A tumor wholly occupying the right thorax was biopsied and diagnosed as pleomorphic sarcoma. The tumor did not respond to chemotherapy, and the patient died of respiratory failure and sepsis. At autopsy, pleomorphic sarcoma was histologically dominant and contained a liposarcoma element confirmed by histocytological and electron microscopic analysis. Adenocarcinoma component with papillary and tubular patterns was confined to the medial lesion of the right lower lobe (3 x 8 cm), which was found in the chest X-ray 3 years before admission, and had continuously merged with the sarcomatous lesion through the histological transition of both components. Aggressive and rapid growth of the sarcoma derived from the earlier adenocarcinoma became prevalent and contributed to the severe clinical outcome. This is the first documented case of primary lung carcinosarcoma with a liposarcoma element.
  • Y Nomura-Takigawa, M Nagano-Fujii, L Deng, S Kitazawa, S Ishido, K Sada, H Hotta
    JOURNAL OF GENERAL VIROLOGY 87 7 1935 - 1945 2006年07月 [有り][無し]
     研究論文(学術雑誌) 
    Non-structural protein 4A (NS4A) of Hepatitis C virus (HCV) functions as a cofactor for NS3 by forming a complex with it to augment its enzymic activities. NS4A also forms a complex with other HCV proteins, such as NS4B/NS5A, to facilitate the formation of the viral RNA replication complex on the encloplasmic reticulum (ER) membrane. In addition to its essential role in HCV replication, NS4A is thought to be involved in viral pathogenesis by affecting cellular functions. In this study, it was demonstrated that NS4A was localized not only on the ER, but also on mitochondria when expressed either alone or together with NS3 in the form of the NS3/4A polyprotein and in the context of HCV RNA replication in Huh7 cells harbouring an HCV RNA replicon. Moreover, NS4A expression altered the intracellular distribution of mitochondria significantly and caused mitochondrial damage, as evidenced by the collapsed mitochondrial transmembrane potential and release of cytochrome c into the cytoplasm, which led ultimately to induction of apoptosis through activation of caspase-3, but not caspase-8. Consistently, Huh7 cells expressing NS3/4A and those harbouring an HCV RNA replicon were shown to be more prone to undergoing actinomycin D-induced, mitochondria-mediated apoptosis, compared with the control Huh7 cells. Taken together, these results suggest the possibility that HCV exerts cytopathic effect (CPE) on the infected cells under certain conditions and that NS4A is responsible, at least in part, for the conditional CPE in HCV-infected cells.
  • Kyousuke Takeuchi, Sohei Kitazawa, Senn Wakahashi, Makoto Sugimoto, Mayumi Morizane, Takeshi Maruo
    INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY 25 3 230 - 232 2006年07月 [有り][無し]
     研究論文(学術雑誌) 
    Although there are several reports of Brenner tumor showing estrogen activities, it is an extremely rare cause of androgen excess leading to virilism, and the source or mechanism of its androgen production is also unknown at present. A 74-year-old woman presented with lower abdominal pain and increased facial hair growth of 6-month duration. Bilateral ovarian tumors were detected, and the patient's serum testosterone (1.7 ng/mL) and estradiol (75 pg/mL) levels were elevated. Bilateral salpingo-oophorectomy was performed. The ovarian tumors were diagnosed as benign Brenner tumor associated with fibrothecoma-like and luteinized stromal cells. Postoperatively, the serum testosterone and estradiol levels decreased. Immunohistochemically, fibrothecoma-like stromal cells were positive for cytochrome P-450 aromatase, which catalyzes the conversion from androgen to estrogen, and negative for c-Jun protein, which has recently reported to attenuate estrogen biosynthesis by directly down-regulating transcription of the aromatase gene. On the other hand, luteinized stromal cells were negative for cytochrome P-450 aromatase and positive for c-Jun protein. It is suggested that androgen is produced mainly in the luteinized stromal cells, because androgen is not converted to estrogen caused by suppression of aromatase biosynthesis by d-Jun.
  • H Kanda, S Tateya, Y Tamori, K Kotani, KI Hiasa, R Kitazawa, S Kitazawa, H Miyachi, S Maeda, K Egashira, M Kasuga
    JOURNAL OF CLINICAL INVESTIGATION 116 6 1494 - 1505 2006年06月 [有り][無し]
     研究論文(学術雑誌) 
    Adipocytes secrete a variety of bioactive molecules that affect the insulin sensitivity of other tissues. We now show that the abundance of monocyte chemoattractant protein-1(MCP-1) mRNA in adipose tissue and the plasma concentration of MCP-1 were increased both in genetically obese diabetic (db/db) mice and in WT mice with obesity induced by a high-fat diet. Mice engineered to express an MCP-1 transgene in adipose tissue under the control of the aP2 gene promoter exhibited insulin resistance, macrophage infiltration into adipose tissue, and increased hepatic triglyceride content. Furthermore, insulin resistance, hepatic steatosis, and macrophage accumulation in adipose tissue induced by a high-fat diet were reduced extensively in MCP-1 homozygous KO mice compared with WT animals. Finally, acute expression of a dominant-negative mutant of MCP-1 ameliorated insulin resistance in db/db mice and in WT mice fed a high-fat diet. These findings suggest that an increase in MCP-1 expression in adipose tissue contributes to the macrophage infiltration into this tissue, insulin resistance, and hepatic steatosis associated with obesity in mice.
  • Junko Naito, Hiroshi Kaji, Hideaki Sowa, Riko Kitazawa, Sohei Kitazawa, Toshihiko Tsukada, Geoffrey N. Hendy, Toshitsugu Sugimoto, Kazuo Chihara
    ENDOCRINE 29 3 485 - 490 2006年06月 [有り][無し]
     研究論文(学術雑誌) 
    In some patients with multiple endocrine neoplasia type 1 (MEN1) it is not possible to identify a germline mutation in the MEN1 gene. We sought to document the loss of expression and function of the MEN1 gene product, menin, in the tumors of such a patient. The proband is an elderly female patient with primary hyperparathyroidism, pancreatic islet tumor, and breast cancer. Her son has primary hyperparathyroidism. No germline loss of heterozygosity at the MEN1 locus and complete lack of menin expression were demonstrated in the proband's tumor tissue. The proband's cultured parathyroid cells lacked the normal reduction in proliferation and parathyroid hormone secretion in response to transforming growth factor-beta. This assessment provided insight into the molecular pathogenesis of the patient and provides evidence for a critical requirement for menin in the antiproliferative action of transforming growth factor-beta.
  • Dun-Fa Peng, Yae Kanai, Morio Sawada, Saori Ushijima, Nobuyoshi Hiraoka, Sohei Kitazawa, Setsuo Hirohashi
    CARCINOGENESIS 27 6 1160 - 1168 2006年06月 [有り][無し]
     研究論文(学術雑誌) 
    To evaluate the significance of alterations in DNA methylation during multistage carcinogenesis of the pancreas, tissue samples of 13 peripheral pancreatic duct epithelia showing no remarkable histological changes without inflammatory background (DE), 20 peripheral pancreatic duct epithelia showing no remarkable histological changes with inflammatory background (DEI), 40 pancreatic intraepithelial neoplasias (PanIN) and 147 areas of ductal carcinoma were microdissected from surgically resected specimens from 58 patients and were embedded into agarose beads. The embedded tissue samples were subjected to methylation-specific PCR (MSP) to evaluate the DNA methylation status of the p14, p15, p16, p73, APC, hMLH1, MGMT, BRCA1, GSTPI, TIMP-3, CDH1 and DAPK-1 genes. The prevalence of DNA methylation of at least one of the 12 genes and the average number of methylated genes were significantly higher in both DEI (60% and 0.85 +/- 0.88, P = 0.0151 and P = 0.0224, respectively) and PanIN (67.5% and 0.95 +/- 0.85, P = 0.0014 and P = 0.0028, respectively) than in DE (15.4% and 0.15 +/- 0.38), and were further increased in ductal carcinoma (98.3% and 2.50 +/- 1.35, P < 0.0001 and P < 0.0001, respectively). The BRCA1, APC, p16 and TIMP-3 genes were frequently methylated in ductal carcinoma (60.3, 58.6, 39.3 and 30.9%, respectively). Considerable heterogeneity of DNA methylation status was observed among multiple microdissected areas from individual ductal carcinomas, and the number of methylated genes per area was significantly correlated with poorer tumor differentiation (P = 0.0249). The average number of methylated genes in ductal carcinomas was significantly correlated with DNMT1 protein expression level (P = 0.0093). These data suggest that accumulation of DNA methylation of multiple tumor-related genes is involved in multistage carcinogenesis of the pancreas from early precancerous stages to malignant progression and that DNMT1 protein overexpression may be responsible for this aberrant DNA methylation.
  • A case of alpha-fetoprotein-producing adenocarcinoma of the endometrium with a hepatoid component as a potential source for alpha-fetoprotein in a postmenopausal woman
    K Takeuchi, S Kitazawa, S Hamanishi, M Inagaki, K Murata
    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER 16 3 1442 - U6 2006年05月 [有り][無し]
     研究論文(学術雑誌) 
    Although case reports of alpha-fetoprotein (AFP)-producing adenocarcinoma other than hepatocellular carcinoma have gradually increased in number, AFP-producing adenocarcinoma of the endometrium is very rare. The patients universally complain of abnormal vaginal bleeding. The patient presented with complaints of epigastric discomfort. No vaginal bleeding was observed. Serum AFP concentration was 453 ng/mL, and lens culinaris agglutinin-reactive AFP percentage of total AFP was increased to 67%. Radiologic imaging and endoscopy did not provide evidence of any primary carcinoma in the liver and gastrointestinal tract. To investigate the unknown origin of high AFP, Pap smear of the endometrium followed by fractional curettage was performed and revealed adenocarcinoma of the endometrium. Radical hysterectomy with pelvic lymph node dissection and partial omentectomy was performed. Histologic study showed a mixture of major AFP-negative endometrioid adenocarcinoma and minor medullary proliferation of the AFP-positive hepatoid adenocarcinoma cells with eosinophilic cytoplasm and hyaline globules. After the surgery followed by four courses of weekly carboplatin and paclitaxel administration, serum levels of AFP dropped into normal range. The possible existence of AFP-producing adenocarcinoma of the endometrium should be considered in a postmenopausal woman even if there is no vaginal bleeding, when AFP-producing tumor is clinically suspected and the imaging studies fail to confirm the diagnosis.
  • K Kishimoto, R Kitazawa, M Kurosaka, S Maeda, S Kitazawa
    HISTOCHEMISTRY AND CELL BIOLOGY 125 5 593 - 602 2006年05月 [有り][無し]
     研究論文(学術雑誌) 
    Based on developmental fate and function, cartilage tissue is broadly classified into transient cartilage (e.g. growth plate, GP) and permanent cartilage (e.g. articular cartilage, AC). The former eventually disappears and is replaced by bone during the endochondral ossification process, whereas the latter retains its permanency. Osteo(chondro)clasts, multinucleated giant cells of the monocyte/macrophage lineage, are selectively induced in the GP during endochondral ossification and play central roles in the resorption of cartilagenous matrices. The aim of this study was to investigate the factors determining the GP-specific recruitment of osteo(chondro)clasts. We especially focused on the expression pattern of the receptor activator of NF-kappa B ligand (RANKL), an essential factor for osteo(chondro)clast differentiation, and on that of epigenetic and transcriptional factors affecting RANKL gene expression. Knee joints of male BALB/c mice aged 8 weeks were dissected and subjected to immunohistochemical analysis using anti-RANKL, Runx2, Dlx5 and Msx2 antibodies. The methylation status of the mouse RANKL gene promoter in both the GP and the AC was analyzed by sodium bisulfite mapping using microdissected mouse tissue. The expression of BMP-2, -3, -4, -6 and type X collagen mRNA was examined by in situ hybridization (ISH). At the boundary between the calcifying cartilage and the hypertrophic chondrocytes of the GP, RANKL-expressing chondrocytes overlapped those expressing Runx2, Dlx5 and Msx2, near numerous osteo(chondro)clasts. Although similar BMP-2 and -4 expression was observed in chondrocytes in both the GP and the AC as well as in maturing osteoblasts, a rather restricted BMP-6 expression pattern was observed in resting and proliferating chondrocytes in the GP. On the other hand, sodium bisulfite mapping showed that mostly non-CpG methylation was similarly scattered in a non-specific manner in chondrocytes in the GP and the AC. Taken together with the fact that putative Runx2 binding elements are located in the RANKL promoter, our data suggest that Runx2, an essential transcription factor for skeletal development, is also a key regulator of RANKL expression in chondrocytes in the GP. Furthermore, a selective and sequential expression of a subset of BMP and of transcription factors may define the expression pattern of RANKL through Runx2.
  • K Takeuchi, S Kitazawa, T Tsujino, S Wakahashi, T Maruo
    EUROPEAN JOURNAL OF GYNAECOLOGICAL ONCOLOGY 27 3 273 - 274 2006年 [有り][無し]
     研究論文(学術雑誌) 
    The first case of uterine bizarre epithelioid lipoleiomyoma with a myxoid component occurring in an 86-year-old woman is described. An intramural 22 cm mass in the anterior wall of the uterine body had a lipoma-like appearance with strands of fibrous tissue. Histologically, the tumor consisted of adipocytes which varied in size and shape, and epithelioid smooth muscle cells with nuclear atypia within a myxoid stroma. No mitotic features were noted despite an extensive search. The patient was well without disease 24 months after hysterectomy. Patients with this type of tumor need close and long-term follow-up because of the paucity of clinical information.
  • S Kitazawa, R Kitazawa
    JOURNAL OF STRUCTURAL BIOLOGY 153 1 64 - 72 2006年01月 [有り][無し]
     研究論文(学術雑誌) 
    In situ hybridization (ISH) is a widely applied technique used for visualizing specific nucleic acid sequences at chromosomal, cytologic, and histologic levels. It sometimes fails, however, to demonstrate precise cell identity, early stages of gene expression and variants of altNSernative splicing because of its limited resolution. To overcome this shortcoming, we have developed an improved ISH technique at the electron microscopic (EM) level by conducting en bloc hybridization before embedding (pre-embedding) and immuno-EM detection after ultra-thin sectioning (post-embedding). We applied this technique to demonstrate both the dynamic expression of interleukin (IL)-6 mRNA immediately after lipopolysaccharide (LPS) treatment, and the static expression of osteonectin mRNA in a differentiating osteoblastic cell linage. Tissue samples were diced into 1 mm cubes, fixed with 4% paraformaldehyde, and then successively hybridized en bloc with the digoxigenin (DIG)-labeled single-stranded probe measuring 200-300 bp with the aid of microwave treatment. After washing, for EM observation, the cubes were embedded in epon for ultra-thin sectioning, and a gold-colloid-labeled anti-DIG antibody was used for post-embedding immuno-EM; some of the cubes was directly incubated with anti-DIG antibody and developed en bloc for stereoscopic and light microscopic observation. IL-6 mRNA during and immediately after transcription was demonstrated in the nuclei of the alveolar macrophages and in neutrophils of mouse lung tissue as early as 15 min after LPS treatment, which was of better sensitivity than that by Northern blot or nuclear run-on techniques. Moreover, in mouse calvaria tissue, osteonectin mRNA both in the nucleus and the cytoplasm was observed in a differentiating osteoblastic cell linage in a differentiation-specific manner. This technique is useful in identifying specific cell types during and immediately after transcribing specific mRNA based on ultrastructural morphology. (C) 2005 Elsevier Inc. All rights reserved.
  • K Takeuchi, M Deguchi, S Hamana, S Motoyama, S Kitazawa, T Maruo
    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER 15 6 1163 - 1165 2005年11月 [有り][無し]
     研究論文(学術雑誌) 
    Angiosarcoma of the vagina is an extremely rare neoplasm and is characterized by frequent recurrence and early metastatic spread. Although previous reports emphasized the poor prognosis of this disease, effective treatment strategies have not been adequately stated. We report a case of angiosarcoma of the vagina, in which the diagnosis was made 9 years after intrapelvic irradiation, and recombinant interleukin-2 (rIL-2) therapy could be effective to suppress the development of distant metastasis. We recommend rIL-2 therapy in combination with irradiation as a palliative therapeutic option for vaginal angiosarcoma when the tumor is inoperable or the patient refuses to undergo surgery. Although vaginal angiosarcoma is an extremely rare condition, its possibility should be borne in mind when finding a vaginal mass in a previously irradiated patient.
  • S Kitazawa, R Kitazawa, T Kondo, K Mori, C Obayashi, T Yamamoto
    JOURNAL OF BONE AND MINERAL RESEARCH 20 9 S320 - S320 2005年09月 [有り][無し]
  • S Kitazawa, T Kondo, R Kitazawa
    NEUROPATHOLOGY 25 3 274 - 279 2005年09月 [有り][無し]
     研究論文(学術雑誌) 
    In situ hybridization (ISH) is a morphology-oriented technique for demonstrating the presence of specific nucleic acid sequences at chromosomal, cytological and histological levels. It is, however, sometimes difficult to recognize specific cell identity, early phase mRNA expression and alternative splicing because of the limited resolution of the light microscope. To overcome this limitation, we developed an improved technique for ISH at the electron microscopic level, in which pre-embedding hybridization with a non-radioactively labeled probe was used, followed by post-embedding immunoglobulin gold colloid staining. By applying this technique, early phase bone morphogenetic protein-3 mRNA in the nuclei and cytoplasm was successfully demonstrated in a differentiating chondrocytic cell lineage. Moreover, with oligo-DNA probes specific for alternative spliced forms of parathyroid hormone-related protein mRNA, we demonstrated such forms in a hyperplastic parathyroid gland attributed to renal failure.
  • Hidajat R, Nagano-Fujii M, Deng L, Tanaka M, Takigawa Y, Kitazawa S, Hotta H
    Journal of General Virology 86 8 2197 - 2208 2005年08月 [有り][無し]
     研究論文(学術雑誌) 
    The NS3 protein of hepatitis C virus (HCV) has a serine protease activity in its N-terminal region, which plays a crucial role in virus replication. This region has also been reported to interact not only with its viral cofactor NS4A, but also with a number of host-cell proteins, which suggests a multifunctional feature of NS3. By means of yeast two-hybrid screening using an N-terminal region of NS3 as bait, a human cDNA encoding a region of ELKS-delta, a member of a novel family of proteins involved in intracellular transport and secretory pathways, was molecularly cloned. Using co-immunoprecipitation, GST pull-down and confocal and immunoelectron microscopic analyses, it was shown that full-length NS3 interacted physically with full-length ELKS-delta and its splice variant, ELKS-alpha, both in the absence and presence of NS4A, in cultured human cells, including Huh-7 cells harbouring an HCV subgenomic RNA replicon. The degree of binding to ELKS-delta varied with different sequences of the N-terminal 180 residues of NS3. Interestingly, NS3, either full-length or N-terminal fragments, enhanced secretion of secreted alkaline phosphatase (SEAP) from the cells, and the increase in SEAP secretion correlated well with the degree of binding between NS3 and ELKS-delta. Taken together, these results suggest the possibility that NS3 plays a role in modulating host-cell functions such as intracellular transport and secretion through its binding to ELKS-delta and ELKS-alpha, which may facilitate the virus life cycle and/or mediate the pathogenesis of HCV.
  • M Fujimoto, R Kitazawa, S Maeda, S Kitazawa
    ONCOGENE 24 32 5108 - 5118 2005年07月 [有り][無し]
     研究論文(学術雑誌) 
    Nerve growth factor and its high-affinity receptor TrkA are thought to be involved in the progression of various cancers. This study investigated the mechanism that regulates aberrant or increased TrkA expression in various cancer cell lines and in the course of pancreatic cancer progression. W e found that the negative cis-acting AP-1-like sequence TGAGCGA was located in the 5'-untranslated region of the TrkA gene. Sodium bisulfite mapping revealed that steady-state TrkA expression correlated positively with the accumulation of methylated CpG around the AP-1-like site. Electrophoretic mobility shift assay showed that the AP-1- like site was bound mainly by c-Jun homodimers; the binding was directly blocked by Sss I methylase-induced methylation or by an excess of oligonucleotides containing consensus AP-1 sequences. Consequently, activation of TrkA gene expression by methylation was considered to be caused by the direct interference of c-Jun binding to the negatively regulating AP-1- like site. Further more, the accumulation of methylated CpG around the AP-1- like site was also observed with increased TrkA immunohistochemical staining in cases of advanced pancreatic adenocarcinoma with extensive perineural invasion. Unlike global methylation at CpG islands that leads to gene silencing, specific methylation at non-CpG islands would play a crucial epigenetic role in the versatility and plasticity of TrkA expression during cancer progression.
  • Kitazawa S, Kitazawa R
    Nippon rinsho. Japanese journal of clinical medicine 63 Suppl 10 409 - 413 2005年 [有り][無し]
  • Hirano M, Yamasaki K, Okada H, Sakurai T, Kondoh T, Katafuchi T, Sugimura K, Kitazawa S, Kitazawa R, Maeda S, Tamura S
    Radiation Medicine - Medical Imaging and Radiation Oncology 23 5 386 - 389 2005年 [有り][無し]
  • R Kitazawa, S Kitazawa
    ACTA HISTOCHEMICA ET CYTOCHEMICA 38 2 143 - 149 2005年 [有り][無し]
     研究論文(学術雑誌) 
    Receptor activator of NF-B-K ligand (RANKL) has been identified as a prerequisite for osteoclastogenesis. To elucidate the molecular mechanism of osteolytic bone lesions, we investigated RANKL mRNA expression in mouse bone tissue from experimental models of mouse autoimmune arthritis and cancer associated osteolysis. Elbow joints of type 11 collagen-induced arthritis (CIA) mice and calvariae of mice transplanted with breast cancer cells under the scalp were fixed with 4% paraformaldehyde for 2 days, decalcified with 20% EDTA in phosphate buffer for 5 days and embedded in paraffin. For in situ hybridization, digoxigenin-labeled antisense (or sense) single-stranded DNA probes were prepared by unidirectional PCR using cDNA of mouse RANKL amplified by RT-PCR. In the articular lesions of CIA mice, TRAP-positive osteoclasts were found at eroded cartilage and bone as well as in the pannus. Synovial cells around these osteoclasts were strongly positive for RANKL, indicating that synovial cells contribute to osteoclastogenesis through authentic RANKL-RANK signaling. In the tumor-induced osteolytic lesions of the mouse calvaria, osteoblasts and stromal cells between the tumor foci and the bone surface expressed RANKL mRNA; osteoclastic bone resorption was observed adjacent to the RANKL-positive cells. Histological evaluation of RANKL expression in bone lesions is important, because osteoclasts and the RANKL-RANK system could be potential targets for therapeutic drugs in diseases with accelerated bone resorption.
  • Hirano M, Yamasaki K, Okada H, Kitazawa S, Kitazawa R, Ohno Y, Sakurai T, Kondoh T, Ohbayashi C, Katafuchi T, Maeda S, Sugimura K, Tamura S
    Radiation Medicine - Medical Imaging and Radiation Oncology 23 2 89 - 96 2005年 [有り][無し]
  • Kitao K, Ohara N, Funakoshi T, Moriyama T, Morita H, Kitazawa S, Maruo T
    Clin Exp Obstet Gynecol 32 4 250  2005年 [有り][無し]
  • Kitao K, Ohara N, Funakoshi T, Moriyama T, Morita H, Kitazawa S, Maruo T
    Clinical and Experimental Obstetrics and Gynecology 32 4 2005年 [有り][無し]
  • K Takeuchi, C Ohbayashi, S Kitazawa, N Ohara, T Maruo
    EUROPEAN JOURNAL OF GYNAECOLOGICAL ONCOLOGY 26 1 109 - 110 2005年 [有り][無し]
     研究論文(学術雑誌) 
    Background: There has been controversy regarding the histogenesis of Brenner tumors. It is generally accepted that Brenner tumors are derived directly from ovarian surface epithelium, which undergoes metaplasia to form the typical urothelial-like components, whereas some investigators assume that Brenner tumors arise from immature germ cells. Case: We describe a well-documented case of the coexistence of struma ovarii regarded as a form of teratoma and Brenner tumor in the same ovary. Immunohistologically, not only columnar cells of thyroid follicles, but also transitional cells of Brenner nests were positive for thyroglobulin. Conclusions: In the present case, Brenner tumors and thyroid elements coexisted and were positive for thyroglobulin. While there is strong evidence that pure Brenner tumors originate mostly from the ovarian surface, at least Brenner tumors associated with teratomatous elements may have a germ cell origin.
  • K Takeuchi, S Kitazawa, M Deguchi, T Maruo
    EUROPEAN JOURNAL OF GYNAECOLOGICAL ONCOLOGY 26 5 511 - 513 2005年 [有り][無し]
     研究論文(学術雑誌) 
    A 83-year-old woman received bilateral salpingo-oophorectomy and hysterectomy due to a provisional diagnosis of ovarian cystic tumor. The tumor had a unilocular cystic cavity demonstrating serous cystadenoma and a solid mural nodule representing a biphasic pattern with mesenchyrnal and glandular components. The glandular elements were composed of benign serous cells, whereas the niesenchymal components consisted of an admixture of fibroinatous stromal cells without atypia and sarcomatous overgrowth. The area of transition from a fibromatous component to sarcomatous overgrowth was identified. After a 2-year follow-up, there were no signs of tumor recurrence or systemic disease. To the authors' knowledge, this is the first reported case of adenofibrosarconia originating from a mural nodule of ovarian serous cystadenoma.
  • Kondo T, Kitazawa R, Maeda S, Kitazawa S
    Journal of Bone and Mineral Research 19 9 1411 - 1419 2004年09月 [有り][無し]
     研究論文(学術雑誌) 
    1alpha,25(OH)(2)D-3 rapidly and transiently suppressed OPG gene expression both by accelerating the degradation of mRNA and by suppressing promoter activity. The latter process was mediated through the AP-1 binding site by a reduction in the proportion of phospho-c-Jun in a JNK-independent manner. Introduction: Osteoclastogenesis is regulated by an integrated network of numerous bone metabolic factors, among which 1alpha,25-dihydroxyvitamin D-3 [1alpha,25(OH)(2)D-3] promotes osteoclastogenesis by reciprocally upregulating the expression of RANKL and downregulating that of osteoprotegerin (OPG). Materials and Methods: To analyze the mechanism by which 1alpha,25(OH)(2)D-3 suppresses OPG, we characterized cis-acting elements of the Mouse OPG gene and assessed the post-transcriptional modifications by actinomycin D assays. Results: 1alpha,25(OH)(2)D-3 rapidly and transiently suppressed OPG expression and shortened the half-life of OPG rnRNA; additionally, the c-Jun homodinier bound to the AP-1 binding site (TGACTGA, -293/-287) and maintained steady-state transcription of the OPG gene. Furthermore, mutation of the AP-1 site negated 1alpha,25(OH)(2)D-3-driven OPG Suppression. Moreover, 1alpha,25(OH)(2)D-3 treatment of ST2 cells decreased the amount of phosphorylated C-Jun protein (phospho-c-Jun), while the total amount of c-Jun remained constant; however, the amount of phosphorylated Jun N-terminal kinase (JNK) was nearly unchanged by 1alpha,25(OH)(2)D-3 treatment. Conclusion: Taken together with the observation that the OPG promoter has no consensus negative vitamin D-responsive elements. these data suggest that 1alpha,25(OH)(2)D-3 transrepresses mouse OPG by reducing the proportion of phospho-c-Jun in a JNK-independent manner. Our data indicated that short-term treatment with 1alpha,25(OH)(2)D-3 effectively downregulated OPG expression both by accelerating the degradation of OPG mRNA and by transrepressing the OPG gene through its AP-1 binding site in the catabolic phase. The OPG gene became insensitive to 1alpha,25(OH)(2)D-3 treatment. however, and reverted to its steady-state expression level over time, leading to the anabolic phase of the effect of 1alpha,25(OH)(2)D-3 on bone.
  • J Zhang, Y Lu, JL Dai, Z Yao, R Kitazawa, S Kitazawa, XP Zhao, DE Hall, KJ Pienta, ET Keller
    PROSTATE 59 4 360 - 369 2004年06月 [有り][無し]
     研究論文(学術雑誌) 
    BACKGROUND. Current animal models of prostate cancer (CaP) bone metastasis do not allow measurement of either tumor growth in bone over time or activation of gene promoters in intraosseous tumors. To develop these methods, we used bioluminescent imaging (BLI) to determine if expression of receptor activator of NF-kappaB ligand (RANKL), a pro-osteoclastogenic factor that promotes CaP bone metastases, is modulated by the bone matrix protein transforming growth factor-beta (TGF-beta) in vivo. METHODS. C4-2B human CaP cells were treated with TGF-beta in vitro and RANKL mRNA and protein production were Measured by polymerase chain reaction (PCR) and ELISA, respectively. Then C4-2B cells stably transfected with the RANKL promoter driving luciferase (lux) were injected intra-tibially into severe combined immundeficient (SCID) mice. Tumors were subjected to BLI every 2 weeks for 6 weeks and serum prostate specific antigen (PSA) was measured using ELISA. Vehicle (V), 1,25 dihydroxyvitamin D (VitD), or TGF-beta was administered to mice with established tumors and BLI to measure RANKL promoter activity was performed. Tumors were then subjected to immunohistochemistry for lux and assayed for RANKL mRNA levels. RESULTS. TGF-beta induced RANKL protein and mRNA expression and activated the RANKL promoter activity in a dose-dependent manner in vitro. BLI demonstrated an increase in intraosseous tumor size over time, which correlated with serum PSA levels. Administration of TGF-beta and VitD to mice with established intraosseous tumors increased lux activity compared to V. Intratibial tumor RANKL mRNA expression paralleled the increased promoter activity. Immunohistochemistry confirmed the presence of lux in the intraosseous tumors. CONCLUSIONS. These results demonstrate the ability to measure intraosseous tumor growth over time and gene promoter activation in an established intraosseous tumor in vivo and also demonstrate that TGF-beta induces activates the RANKL promoter. These results provide a novel method to explore the biology of CaP bone metastases. (C) 2003 Wiley-Liss, Inc.
  • Ong D.B, Colley S.M, Norman M.R, Kitazawa S, Tobias J.H
    Journal of Bone and Mineral Research 19 3 447 - 454 2004年03月 [有り][無し]
     研究論文(学術雑誌) 
    The effects of 17beta-estradiol (E-2) and ICI 182,780 (ICI) on activity of a BMP-6 promoter were compared in osteoblast-like and breast cancer cells transiently transfected with ERalpha. E-2 but not ICI stimulated BMP-6 reporter activity in breast cancer cells, whereas the opposite was observed in osteoblast-like cells, associated with lack of AF-2 dependence of the response, and absent intranuclear localization of ERalpha, suggesting the involvement of a distinct ERalpha-dependent response mechanism in osteoblasts. Introduction: Previous studies suggest that the tissue-selective effect of antiestrogens on bone reflects the ability of these compounds to target certain osteoblast regulatory genes. To explore this hypothesis, we examined whether antiestrogens preferentially stimulate the bone morphogenetic protein 6 (BMP-6) promoter in bone cells, and if so, whether this activity is associated with a distinct estrogen receptor (ER)alpha-dependent response mechanism to that in other cell types. Materials and Methods: We compared the effects of 17beta-estradiol (E-2) and ICI 182,780 (ICI) on activity of a 4.3-kb BMP-6 reporter construct in osteoblast-like cells (human MG63 and SaOS-2 cells and rat ROS 17/2.8 cells), human MCF-7 and T47-D breast cancer cell lines, and HepG2 hepatoma cells, after transient transfection with ERalpha, ERbeta, and mutant ER constructs. Results: E-2, but not ICI, stimulated BMP-6 reporter activity by approximately 100% in MCF-7, T47-D cells, and HepG2 cells when transfected with ERa. In contrast, in ERalpha-transfected osteoblast-like cells, an increase in reporter activity of approximately 75% was observed after treatment with ICI but not E-2. The response of MG63 cells to ICI and MCF-7 cells to E-2 both required ERalpha as opposed to ERbeta and the ERalpha activation function (AF)-1 activation domain. However, whereas the AF-2 domain was also required for E-2 to stimulate reporter activity in MCF-7 cells, the response to ICI in MG63 cells was AF-2 independent. In further studies where we compared the intracellular distribution of ERalpha associated with these responses, E-2-dependent stimulation of the BMP-6 reporter in MCF-7 cells was associated with intranuclear localization of ERalpha, whereas extranuclear localization was seen in rat osteosarcoma cells (ROS) cells treated with ICI. Conclusions: Antiestrogens selectively stimulate BMP-6 reporter activity in osteoblast-like cells through a distinct ERa-dependent mechanism characterized by independence of the AF-2 domain and extranuclear localization of ERalpha.
  • Sowa H, Kaji H, Kitazawa R, Kitazawa S, Tsukamoto T, Yano S, Tsukada T, Canaff L, Hendy G.N, Sugimoto T, Chihara K
    Cancer Research 64 6 2222 - 2228 2004年03月 [有り][無し]
     研究論文(学術雑誌) 
    Primary hyperparathyroidism is a common endocrine disorder caused by parathyroid gland enlargement and excessive parathyroid hormone (PTH) secretion. However, the precise mechanisms of tumorigenesis of the parathyroids are unknown. Here we have investigated the roles of transforming growth factor (TGF)-beta and menin, the product of the multiple endocrine neoplasia type 1 (Men1) gene, in the proliferation and PTH production of parathyroid cells from either patients with secondary hyperparathyroidism or Men1. TGF-beta was expressed in the parathyroid endocrine cells. Addition of TGF-beta to parathyroid cells from patients with secondary hyperparathyroidism inhibited their proliferation and PTH secretion. These responses to TGF-beta were lost when menin was specifically inactivated by antisense oligonucleotides. Moreover, TGF-beta did not affect the proliferation and PTH production of parathyroid cells from a Men1 patient. These results indicate that menin is required for TGF-beta action in the parathyroid. We conclude that TGF-beta is an important autocrine/paracrine negative regulator of parathyroid cell proliferation and PTH secretion and that loss of TGF-beta signaling due to menin inactivation contributes to parathyroid tumorigenesis.
  • Kobayashi N, Kitazawa R, Maeda S, Schurgers L, Kitazawa S
    Kobe J Med Sci 50 3-4 69 - 81 2004年 [有り][無し]
  • Kobayashi N, Kitazawa R, Maeda S, Schurgers L.J, Kitazawa S
    Kobe Journal of Medical Sciences 50 3-4 69 - 81 2004年 [有り][無し]
  • K Kitao, N Ohara, T Funakoshi, T Moriyama, T Maruo, M Yamane, N Yokoyama, T Kondo, S Kitazawa
    JOURNAL OF PERINATAL MEDICINE 32 6 527 - 531 2004年 [有り][無し]
     研究論文(学術雑誌) 
    Noncompaction of the left ventricular myocardium (NCLV) is an uncommon congenital cardiomyopathy with poor prognosis. We describe a case of NCLV that developed in a pregnant woman and her neonate. A nulliparous woman was referred at 24 weeks' gestation due to dyspnea and fetal hydrops. Maternal echocardiography demonstrated NCLV with characteristic findings of prominent and excessive ventricular trabeculations and deep intertrabecular recesses in the left ventricle. An M-mode echocardiography suggested depressed left ventricular systolic function. A fetal echocardiography at 24 weeks' gestation demonstrated cardiomegaly, but morphologic findings were not definitive for NCLV. An emergency cesarean section was performed due to maternal heart failure. A neonatal echocardiography diagnosed NCLV with depressed left ventricular systolic function. The neonate died of cardiac failure on the second day of life. Autopsy confirmed the echocardiographic findings. Since patients with NCLV may develop heart failure, multidisciplinary management is mandatory. In addition, awareness of familial occurrence of NCLV should be kept in mind for early diagnosis in the fetus and neonate.
  • Hirano M, Yamasaki K, Kitazawa R, Kitazawa S, Okada H, Katafuchi T, Sakurai T, Kondoh T, Ohbayashi C, Maeda S, Sugimura K, Tamura S
    Radiation medicine 22 1 56 - 59 2004年 [有り][無し]
  • M Saijo, R Kitazawa, M Nakajima, M Kurosaka, S Maeda, S Kitazawa
    HISTOCHEMISTRY AND CELL BIOLOGY 120 6 493 - 503 2003年12月 [有り][無し]
     研究論文(学術雑誌) 
    Bone fracture healing takes place through endochondral ossification where cartilaginous callus is replaced by bony callus. Vascular endothelial growth factor (VEGF) is a requisite for endochondral ossification, where blood vessel invasion of cartilaginous callus is crucial. Heparanase is an endoglucuronidase that degrades heparan sulfate proteoglycans (HSPG) and releases heparin-binding growth factors including VEGF as an active form. To investigate the role of heparanase in VEGF recruitment during fracture healing, the expression of heparanase mRNA and VEGF, and vessel formation were examined in mouse fractured bone. On days 5 and 7 after the fracture, when mesenchymal cells proliferated and differentiated into chondrocytes, heparanase mRNA was detected in osteo(chondro)clasts and their precursors, but not in the inflammatory phase (day 3). On day 10, both VEGF and HSPG were produced by hypertrophic chondrocytes of the cartilaginous callus and by osteoblasts of the bony callus; numerous osteo(chondro)clasts resorbing the cartilage expressed strong heparanase signals. Adjacent to the cartilage resorption sites, angiogenesis with CD31-positive endothelial cells and osteogenesis with osteonectin-positive osteoblasts were observed. On days 14 and 21, osteoclasts in the woven bone tissue expressed heparanase mRNA. These data suggest that by producing heparanase osteo(chondro)clasts contribute to the recruitment of the active form of VEGF. Thus osteo(chondro)clasts may promote local angiogenesis as well as callus resorption in endochondral ossification during fracture healing.
  • S Kitazawa, K Kajimoto, T Kondo, R Kitazawa
    JOURNAL OF CELLULAR BIOCHEMISTRY 89 4 771 - 777 2003年07月 [有り][無し]
     研究論文(学術雑誌) 
    Receptor activator of NF-kappaB ligand (RANKL) has been identified as requisite for osteoclastogenesis. To elucidate the molecular mechanism that conducts its catabolic action on bone, the effect of 1alpha,25 dihydroxyvitamin D-3 (1alpha,25(OH)(2)D-3) on osteoclastogenesis and RANKL mRNA expression was examined by coculture, RT-PCR and nuclear run-on studies. By accelerating the transcription rate of the RANKL gene in SaOS2 osteoblastic cells, 1alpha,25(OH)(2)D-3 enhanced in vitro osteoclast formation from peripheral monocytes. Cloning and characterization of the 5'-flanking region of the human RANKL gene revealed that the basic promoter comprises inverted TATA- and CAAT-boxes flanked by RUNX2 binding sites. Both electrophoresis mobility shift assay (EMSA) and transfection studies demonstrated that 1alpha,25(OH)(2)D-3 activated human RANKL promoter through vitamin D responsive elements (VDRE) located at -1584/-1570 by binding VDR and RXRalpha heterodimers in a ligand-dependent manner. The results provide direct evidence that 1alpha,25(OH)(2)D-3 augments osteoclastogenesis by transactivating the human RANKL gene in osteoblastic cells through VDRE. (C) 2003 Wiley-Liss, Inc.
  • T Yamada, K Takeuchi, Y Masuda, T Moriyama, S Kitazawa, T Maruo
    FETAL DIAGNOSIS AND THERAPY 18 3 137 - 139 2003年05月 [有り][無し]
     研究論文(学術雑誌) 
    A case of fetal brain tumor, which appeared after 32 weeks' gestation, is presented. Prenatal ultrasonography and magnetic resonance imaging demonstrated a large heterogeneous mass in the right supratentorial region and left enlarged ventricle. A male fetus weighing 2,616 g was delivered at 34 weeks gestation by cesarean section and died on the 37th day of life due to rapid growth of the tumor. Following autopsy, the pathohistological examination revealed primitive neuroectodermal tumor. Magnetic resonance imaging in the prenatal management of the congenital brain tumor is efficient in evaluating the expansion and margin of the tumor and intratumoral bleeding, which are not demonstrated by ultrasonography. Copyright (C) 2003 S. Karger AG, Basel.
  • A Darwanto, R Kitazawa, S Maeda, S Kitazawa
    CANCER SCIENCE 94 5 442 - 447 2003年05月 [有り][無し]
     研究論文(学術雑誌) 
    Reduced expression of E-cadherin (E-cad) owing to aberrant 5'CpG island hypermethylation has been regarded as one of the main molecular events involved in the dysfunction of the cell-cell adhesion system. The molecular mechanisms providing diversity and heterogeneity of E-cad expression in colorectal carcinoma were explored. In 29 cases of colorectal carcinoma in Indonesia, the expression of E-cad was analyzed by immunohistochemical staining, the methylation status of the E-cad promoter was determined by methylation-specific PCR, and the expression of methyl-CpG-binding protein (MeCP) 2 was studied by in situ hybridization. E-cad expression was strong, and no methylation was observed in normal colon mucosa and most of the well differentiated adenocarcinoma. In contrast, both signet-ring cell carcinoma and mucinous adenocarcinoma showed fully methylated patterns and strong MeCP2 expression. In moderately- and poorly-differentiated adenocarcinomas, however, E-cad expression was rather heterogeneous, especially at the front of invasion and in the dissociated areas, where loss of MeCP2 expression correlated with E-cad reexpression even in the presence of E-cad promoter methylation. We conclude that both CpG methylation of the E-cad promoter and significant MeCP2 expression cooperatively and epigenetically regulate E-cad expression in colorectal cancer.
  • S Yano, T Sugimoto, T Tsukamoto, K Chihara, A Kobayashi, S Kitazawa, S Maeda, R Kitazawa
    EUROPEAN JOURNAL OF ENDOCRINOLOGY 148 4 403 - 411 2003年04月 [有り][無し]
     研究論文(学術雑誌) 
    Objective: A significant decrease in vitamin D receptor (VDR) and calcium-sensing receptor (CaSR) protein expression has been demonstrated recently in parathyroid (PT) adenomas. In this study, we investigated the relationships between the proliferative activity of parathyroid glands (PTGs) and the expression of VDR as well as CaSR, and compared it with the, clinical severity in patients with primary hyperparathyroidism (1degreesHPT). Design: Seven patients with 1degreesHPT were included in this study. Four patients with thyroid carcinoma served as controls. Methods: Immunohistochemical staining was performed on serial sections of PTGs with specific antibodies against CaSR, VDR, and Ki67. Areas examined in each section were selected at random in relation to the gland size. The number of Ki67-positive cells was expressed as a labeling index (LI; positive cells per 1000 PT cells). The expression of CaSR and VDR was semi-quantitatively analyzed based on the intensity of staining. After averages of the scores from all areas were calculated, CaSR and VDR scores, and Ki67 LI were assigned to each gland for use in statistical analyses. Results: In PT adenomas, scores of VDR and CaSR were markedly lower than in normal PTGs (P < 0.01), while the proportion of Ki67-positive cells in PT adenomas was significantly higher than in normal PTGs (P < 0.01). Single regression analyses revealed that Ki67 LI was positively correlated with serum levels of intact parathyroid hormone and Ca, and PTG weight (R = 0.70, P < 0.05, R = 0.78, P < 0.01 and R = 0.84, P < 0.05 respectively). Ki67 LI was negatively correlated with CaSR and VDR scores (R = -0.78, P < 0.01 and R = -0.72, P < 0.05 respectively). Moreover, there was a strong positive relationship between CaSR and VDR expression (R = 0.95, P < 0.001). Conclusions: Marked decreases in VDR and CaSR expression could, at least in part, be responsible for the high proliferation of PT cells and the pathological progression of 1degreesHPT.
  • Gohji K, Kitazawa S
    Prostate Cancer: Science and Clinical Practice 11 - 27 2003年 [有り][無し]
  • Hirano M, Yamasaki K, Sakurai T, Kondoh T, Ryu Y, Okada H, Sugimura K, Kitazawa S, Kitazawa R, Maeda S, Katafuchi T, Tamura S
    Igaku butsuri : Nihon Igaku Butsuri Gakkai kikanshi = Japanese journal of medical physics : an official journal of Japan Society of Medical Physics 23 2 157 - 159 2003年 [有り][無し]
  • T Nakajima, Y Konda, M Kanai, Y Izumi, N Kanda, A Nanakin, S Kitazawa, T Chiba
    DIGESTIVE DISEASES AND SCIENCES 47 12 2729 - 2737 2002年12月 [有り][無し]
     研究論文(学術雑誌) 
    We investigated the expression of parathyroid hormone-related peptide (PTHrP) and the relationship between PTHrP and its endoprotease furin in gastric cancer. PTHrP was colocalized with furin in 75% of gastric cancer tissues (six of eight) from patients with high serum PTHrP levels. PTHrP mRNA expression was confirmed in 67% of gastric cancer cell lines (four of six), whereas furin mRNA was detected in all six gastric cancer cell lines. In a cultured gastric cancer cell line, MKN28, mature PTHrP protein expression was markedly increased by transfection of furin cDNA. Furin cDNA-transfected MKN28 cells grew faster than did the mock controls. Moreover, furin mRNA expression in cultured gastric cancer cells was enhanced when PTHrP was added to the culture medium. These results suggest a link between PTHrP and furin in the regulation of gastric cancer cell growth. Furin might be involved not only in the production of the mature form of PTHrP, but also in promoting growth in gastric cancer cells.
  • S Kitazawa, R Kitazawa
    JOURNAL OF PATHOLOGY 198 2 228 - 236 2002年10月 [有り][無し]
     研究論文(学術雑誌) 
    Breast cancer is frequently associated with osteolytic bone metastasis, where osteoclasts play a major role in bone destruction. Recently, osteoclast differentiation factor (RANKL) has been identified as a prerequisite for the formation and maintenance of osteoclasts from haematopoietic precursors. To elucidate the mechanism of osteoclastogenesis and bone destruction in bone-residing breast cancer, PTHrP-producing (MCF-7) and -non-producing (MCF-7UP) human breast cancer cells were subcutaneously injected into the forehead of nude mice maintained without oestrogen supplement. One, two, and three weeks thereafter, the expression of RANKL and PTHrP mRNA, and osteoclastogenesis were analysed by in situ hybridization and TRAP staining. In MCF-7 cells, at early stages, spindle-shaped stromal cells and osteoblasts on the bone surface expressed RANKL, then numerous osteoclasts were induced on the periosteal bone surface. Three weeks after the transplantation, MCF-7 cancer cells migrated onto the eroded bone surface, where they survived apoptosis. At all stages, RANKL expression was confined to the stromal/osteoblastic cells, whereas PTHrP was confined to the MCF-7 breast cancer cells. On the other hand, PTHrP was negative in MCF-7UP cells at all stages, and neither induction of osteoclasts nor infiltrative growth of cancer cells was observed. Moreover, in vitro treatment with PTHrP resulted in increased RANKL mRNA expression and transcription activity in the MC3T3-E1 mouse osteoblastic cell line. Thus PTHrP induces osteoclastic bone resorption through the transactivation of the RANKL gene on stromal/osteoblastic cells, affording a bone microenvironment conducive to the survival of PTHrP-producing cancer cells. Copyright (C) 2002 John Wiley Sons, Ltd.
  • Kitazawa S, Kitazawa R
    Biochemical and Biophysical Research Communications 293 1 126 - 131 2002年04月 [有り][無し]
     研究論文(学術雑誌) 
    Receptor activator of NF-kappaB ligand (RANKL) is a membrane-bound signal transducer requisite for differentiation and maintenance of osteoclasts. RANKL expression on stromal/osteoblastic cells is tightly regulated to maintain physiological serum calcium levels and bone mass. These stromal/osteoblastic cells, however, comprise a rather heterogeneous population ranging from immature mesenchymal cells to mature osteoblasts and also respond differently to bone resorptive stimuli. In the mouse coculture system, we also have demonstrated the passage-dependent difference of cultured mouse stromal cells in supporting osteoclastogenesis due to altered RANKL gene expression. To address the issue of what molecular mechanism gives the diversity of RANKL gene expression to stromal/osteoblastic cells, we characterized the mouse RANKL gene promoter that contains two CpG clustering regions; one around the transcription start site, and the other downstream of the vitamin D response element (VDRE). Using earlier- and later-passage mouse ST2 cells. we analyzed the CpG methylation status by sodium bisulfite mapping and found that CpG loci around the transcription start site (-66/+246) were predominantly methylated in later-passage ST2 cells. Moreover, earlier- and later-passage ST2 cells transfected with a RANKL promoter construct showed the same steady-state level of luciferase activity and of the inducible effect of 1.25(OH)(2)D-3. Furthermore, the introduction of methylation to the promoter construct silenced promoter activity. The results suggest that CpG methylation around the transcription start site of the mouse RANKL gene is an important epigenetic event, and that its heterogeneity might cause the diversity of the stromal/osteoblastic cells in RANKL gene expression. (C) 2002 Elsevier Science (USA). All rights reserved.
  • H Mori, R Kitazawa, S Mizuki, M Nose, S Maeda, S Kitazawa
    HISTOCHEMISTRY AND CELL BIOLOGY 117 3 283 - 292 2002年03月 [有り][無し]
     研究論文(学術雑誌) 
    Rheumatoid arthritis (RA) is a systemic disorder characterized by synovial inflammation and subsequent destruction and deformity of synovial joints. The articular lesions start with synovitis, focal erosion of unmineralized cartilage, and then culminate in the destruction of subarticular bone by pannus tissue. Periarticular osteopenia and systemic osteoporosis follow as late complications of RA. Osteoclasts, specialized cells that resorb bone, play a central role in developing these osteolytic lesions. To elucidate the mechanism of osteoclastogenesis and bone destruction in autoimmune arthritis, we investigated the expression of RANK ligand (RANKL), RANK, and osteoprotegerin (OPG) mRNA in a mouse type II collagen-induced arthritis (CIA) model by in situ hybridization. The results indicated that most of the TRAP-positive mono- and multinucleated cells in the inflamed and proliferating synovium and in the pannus were RANK-positive authentic osteoclasts and their precursors. In the inflamed synovium and pannus of the mouse CIA model, synovial fibroblastic cells around these RANK-positive cells were strongly positive for RANKL. Moreover, RANKL-positive osteoblasts on the endosteal bone surface, at a distance from the affected synovial joints, increased significantly in the mouse CIA model prior to periarticular osteopenia and systemic osteoporosis. These data indicated that the RANKL-RANK system plays an important role for osteoclastogenesis in both local and systemic osteolytic lesions in autoimmune arthritis, and can therefore be a good target for therapeutic intervention.
  • Yamazaki K, Matsui J, Kagoshima Y, Tusaka Y, Suzuki Y, Hirano M, Ohbayashi C, Kitazawa S, Kitazawa R, Maeda S, Fukushima K, Tamura S, Hishikawa Y, Nagai H, Katabuchi T, Sugiyama K
    Igaku Butsuri 22 1 8 - 12 2002年 [有り][無し]
  • Morita M, Tani S, Hagihara R, Ryu Y, Yagi N, Yamashita J, Imanishi K, Kitazawa S
    Nippon Shokakibyo Gakkai Zasshi 99 4 391 - 6 2002年 [有り][無し]
  • R Kitazawa, S Kitazawa
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 290 2 650 - 655 2002年01月 [有り][無し]
     研究論文(学術雑誌) 
    Receptor activator of NF-B-kappa ligand (RANKL) is a membrane-bound signal transducer necessary for the induction and maintenance of osteoclasts. To clarify the molecular mechanism by which 1,25-dihydroxyvitamin D-3 (1,25-(OH)(2)D-3) augments osteoclasts, we characterized the promoter region of the mouse RANKL gene. Mirroring in vitro osteoclastogenesis demonstrated by a coculture of bone marrow macrophages with ST2 stromal cells, Northern blot, and nuclear run-on analyses showed that 1,25-(OH)(2)D-3 upregulate RANKL gene expression at the transcriptional level. Using a series of deletion mutants of mouse RANKL promoter-luciferase reporter gene constructs, transient transfection studies revealed that the inductive effect of 1,25-(OH)(2)D-3 was abolished when the region up to -723 was deleted. Am electrophoretic motility shift assay demonstrated that the VDR-RXRbeta heterodimer bound to (AGGTCA) under bar GCC (TGGTTCA) under bar (-937/-922), and VDRE/nuclear protein super-shift complexes that bound to anti-VDR and -RXRbeta antibodies were detected in the nuclear extract of 1,25-(OH)(2)D-3-treated ST2 cells. Furthermore, induction of mutation to the putative VDRE also diminished the inductive effect of 1,25-(OH)(2)D-3. We therefore concluded that mouse RANKL gene is one of the target genes of 1,25-(OH)(2)D-3 containing a functional VDRE in the promoter region. (C) 2002 Elsevier Science.
  • R Kitazawa, S Kitazawa, S Maeda, A Kobayashi
    HISTOLOGY AND HISTOPATHOLOGY 17 1 179 - 184 2002年 [有り][無し]
     研究論文(学術雑誌) 
    Parathyroid hormone-related protein (PTHrP), a factor responsible for malignancy associated hypercalcemia, plays a physiological roles such as bone development and placental calcium transport. The expression of PTHrP in adult human parathyroid tissues under normal and pathological conditions was analyzed. By immunohistochemistry, PTHrP expression was detected in 86% of normal parathyroid (12/14 cases), 74% of adenomas (14/19) and 89% of hyperplasia secondary to chronic renal failure (16/18). PTHrP protein was observed mainly in the cytoplasm of oxyphil cells, consistent with the localization of its mRNA demonstrated by in situ hybridization. The rate of PTHrP-positive cells was higher in areas consisting of oxyphil cells than in those of non-oxyphil cells, regardless of whether the parathyroid was normal or pathological. In the normal parathyroid, an age-related increase in PTHrP expression was observed with a relative increase in oxyphil cells, reflecting aging and deterioration of parathyroid tissue. In adenoma, cases with a predominance of oxyphil cells expressed PTHrP, whereas clear cell adenoma did not. In secondary hyperplasia, the rate of PTHrP-expressing cells was higher than in normal parathyroid or adenoma, with varying levels of expression among nodules. We speculate that PTHrP could act through the paracrine/ autocrine mechanism to regulate proliferation and differentiation of normal and neoplastic parathyroid cells.
  • R Kitazawa, S Kitazawa, K Kajimoto, H Sowa, T Sugimoto, T Matsui, K Chihara, S Maeda
    PATHOLOGY INTERNATIONAL 52 1 63 - 68 2002年01月 [有り][無し]
     研究論文(学術雑誌) 
    Multiple myeloma is a plasma cell neoplasia often associated with multiple skeletal lesions and hypercalcemia. Several cytokines, including interleukin (IL)-1, IL-6 and tumor necrosis factor-beta (TNF-beta), derived from myeloma cells are thought to accelerate osteoclastic bone resorption and cause hypercalcemia through a paracrine mechanism. We report on a case of a 69-year-old man with multiple myeloma associated with hypercalcemia and advanced osteolytic lesions. After bisphosphonate treatment and MP (melphalan and prednisolone) therapy, the patient's serum calcium level was successfully but transiently recovered to the normal range. Biochemical analysis showed a remarkable increase in serum parathyroid hormone-related protein (PTHrP; 3.7 pmol/L) and IL-6 (22.0 pg/mL). On the other hand, parathyroid hormone and 1alpha,25(OH)(2) vitamin D-3 were suppressed. By immunohistochemistry and in situ hybridization on aspiration-biopsied bone marrow clot sections, PTHrP mRNA and protein were detected in the cytoplasm of myeloma cells. The rate of PTHrP-positive myeloma cells was estimated to be at least one-third. Since PTHrP can, as an endocrine factor, systemically act on bone and kidney, hypercalcemia in this case might have been caused through both local osteolytic hypercalcemia and humoral hypercalcemia of malignancy mechanisms.
  • Morita M, Tani S, Hagihara R, Ryu Y, Yagi N, Yamashita J, Imanishi K, Kitazawa S
    Japanese Journal of Gastroenterology 99 4 391 - 396 2002年 [有り][無し]
  • K Gohji, M Okamoto, S Kitazawa, M Toyoshima, J Dong, Y Katsuoka, M Nakajima
    JOURNAL OF UROLOGY 166 4 1286 - 1290 2001年10月 [有り][無し]
     研究論文(学術雑誌) 
    Purpose: We determined the association of heparanase protein and messenger (m)RNA expression with bladder cancer invasion and metastasis. Materials and Methods: The expression of heparanase protein and mRNA was assessed by immunohistochemical staining and in situ hybridization, respectively, in 67 bladder cancer specimens resected at various stages of disease. To our knowledge this is the first systematic study of heparanase protein and mRNA expression in human bladder cancer. Results: The expression of heparanase protein in muscular invasive bladder cancer was significantly higher than in superficial cancer (68% versus 19%, p = 0.0001). It was higher in the primary tumor of patients with lymph node metastatic cancer than those with nonmetastatic cancer (80% versus 37%, p = 0.0006). In high grade disease it was significantly higher than in low grade disease (79% versus 29%, p = 0.0001). The expression of heparanase mRNA was also significantly higher in stage pT3 or greater than in stage pT2 or less bladder cancer (96% versus 33%, p = 0.0003). In metastatic N+ cases it was significantly higher than in nonmetastatic bladder cancer (93% versus 46%, p = 0.0037). The heparanase gene and protein showed similar patterns of expression in bladder cancer. Conclusions: Our study implies that the expression of heparanase protein and mRNA is associated with bladder cancer invasion and metastasis, and heparanase may have a role in disease progression.
  • K Gohji, H Hirano, M Okamoto, S Kitazawa, M Toyoshima, J Dong, Y Katsuoka, M Nakajima
    INTERNATIONAL JOURNAL OF CANCER 95 5 295 - 301 2001年09月 [有り][無し]
     研究論文(学術雑誌) 
    The relationship between expression of extracellular matrix degradative enzymes, angiogenesis and survival of multistage bladder cancer was determined. Expression of 3 extracellular matrix degradative enzymes (metalloproteinase-2, -9 and heparanase) and microvessel formation were examined in 40 resected bladder cancer specimens by immunohistostochemic staining, and then the association of the enzyme expression with angiogenesis and various stages of cancer was investigated. Heparanase protein expression in muscular invasive or lymphnode metastatic cancer was significantly higher than in superficial or nonmetastatic cancer, respectively (69% vs. 8%, p < 0.001, and 80% vs. 40%, p = 0.028, respectively). Interestingly, heparanase was expressed at much higher levels than matrix metalloproteinase-2 and -9. The mean microvessel count in cancers with heparanase expression was significantly higher than that in cancers without heparanase expression (32.3 +/- 18.2 vs. 5.5 +/- 6.1, p = 0.0008). The microvessel formation was not associated with the expression of matrix metalloproteinase-2 and -9. The cancer-specific and overall survival rates of patients with heparanase expression were significantly lower than those of patients without it (p = 0.0001 and p = 0.0008, respectively). Multivariate analysis showed that heparanase expression was a significantly independent prognostic factor for both cancer-specific (p = 0.0047) and overall survival (p = 0.0200). Our study suggested that heparanase plays important roles in invasion, angiogenesis and metastasis of bladder cancer, and thus, this molecule could be a new molecule to inhibit invasion, angiogenesis and metastasis of bladder cancer. Moreover, our results indicate that expression of heparanase could be a new prognostic factor of this disease. (C) 2001 Wiley-Liss, Inc.
  • Onishi T, Yamakawa K, Franco O.E, Kawamura J, Watanabe M, Shiraishi T, Kitazawa S
    Biochimica et Biophysica Acta - Molecular Cell Research 1538 2-3 218 - 227 2001年04月 [有り][無し]
     研究論文(学術雑誌) 
    Metastatic diseases of prostate cancer reveal high expression of alpha6 integrin and the activation of mitogen-activated protein kinases (MAP kinase). Therefore, the present study was conducted to examine whether MAP kinase pathway is involved in the alpha6 integrin gene expression in androgen-independent prostate cancer cell lines. alpha6 integrin mRNA expression, the alpha6 integrin promoter-induced luciferase activities and MAP kinase enzyme activities in androgen-independent LNCaP and PC-3 cell lines were higher than those in androgen-dependent LNCaP. Deletion and mutation analysis showed that Spl consensus sequence at -48 to -43 bp from the transcription start site was necessary for basal promoter activity. Binding of Spl to its consensus sequence in three cell lines was confirmed by electrophoretic mobility shift assays. Spl binding to its consensus sequence, as well as promoter activity and mRNA expression, were found to be inhibited by an inhibitor of MAP kinase kinase 1 and 2, U0126, in the androgen-independent cell lines. Our results indicate that the proximal Spl is necessary for basal promoter activity of the alpha6 integrin, suggesting that signal transduction from MAP kinases Co activation of Spl might be involved in a6 integrin gene expression in androgen-independent prostate cancer cell lines. (C) 2001 Elsevier Science B.V. Ah rights reserved.
  • K Gohji, S Kitazawa, H Tamada, Y Katsuoka, M Nakajima
    JOURNAL OF UROLOGY 165 3 1033 - 1036 2001年03月 [有り][無し]
     研究論文(学術雑誌) 
    Purpose: We determined the role of endothelin receptors in prostate cancer progression. Materials and Methods: We examined 51 prostate cancer specimens obtained at surgery or biopsy for the relationship of endothelin receptor expression determined by immunohistochemical staining with malignant potential. Results: The positive staining rate of endothelin receptor A in the 51 specimens was significantly higher than of endothelin B (71% versus 24%, p <0.0001). The staining rate of receptor A in Gleason score 5 to 10 disease was significantly higher than in Gleason 2 to 4 disease (91% versus 29%, p <0.0001). The overall staining rate of endothelin receptor A in nonorgan confined disease without bone metastasis but with extraprostatic disease was 87% in 23 cases, including 16 of 19 stage T3 (84%) and all 4 stage T4 (100%) cases. This rate was significantly higher than that of organ confined cancer (29%, p = 0.0003). All patients with bone metastasis had positive staining for endothelin receptor A. An especially high rate of intensely positive staining was observed for endothelin receptor A in biopsy specimens with bone metastasis or Gleason sum 8 to 10. Moreover, positive staining was stronger in cancer cells penetrating the prostatic capsule than in those at the primary foci. However, the positive staining rate of endothelin receptor B was not significantly different in organ and nonorgan confined cancer without bone metastasis (12% versus 26%, p = 0.4284), bone metastatic and nonmetastatic cancer (20% versus 36%, p = 0.2619) or the Gleason sum groups (p = 0.0874). Conclusions: Our results indicate that endothelin receptor A expression may serve as a marker for and have an important role in prostate cancer progression.
  • H Tamada, R Kitazawa, K Gohji, S Kitazawa
    JOURNAL OF BONE AND MINERAL RESEARCH 16 3 487 - 496 2001年03月 [有り][無し]
     研究論文(学術雑誌) 
    Bone morphogenetic proteins (BMPs), belonging to the transforming growth factor-beta (TGF-beta) superfamily, are multifunctional molecules that regulate bone induction and organ development. Among BMPs, BMP-6 has been shown to be overexpressed in prostate cancer and is speculated to be associated with bone-forming skeletal metastasis. We investigated the regulatory mechanism of the BMP-6 gene expression in prostate cancer cell lines DU-145, LNCaP, PC-3, and PC-3M with regard to the methylation status of the CpG island in the 5' Banking region of the human BMP-6 gene. By sequence-specific analysis of methylated cytosines, we show here that the methylation status of the CpG loci around the Sp1 site of the BMP-6 promoter is related to its steady-state expression and an alternative splicing of messenger RNA (mRNA) in prostate cancer cell lines. Furthermore, a study of clinical cases of benign and malignant prostate lesion by in situ hybridization showed that BMP-6 expression was high at both primary and secondary sites in cases of advanced cancer with metastasis. Demethylation of the CPG loci around the Spl binding site was shown in cases with high BMP-6 expression by sequencing analysis of the methylated cytosine from paraffin-embedded materials, Our results suggested that during cancer progression, besides inactivation of tumor suppressor genes by hypermethylation, activation of certain genes like BMP-6 by selective demethylation was a common epigenetic event giving a variable character to the invading and metastasizing cancer cells.
  • Sakamoto Y, Kitazawa R, Maeda S, Kitazawa S
    Journal of Cellular Biochemistry 80 3 415 - 423 2001年 [有り][無し]
     研究論文(学術雑誌) 
    The APC genetic locus has been linked to the tumorigenesis and progression of colorectal cancer, although the precise mechanism of its involvement in this disease remains unknown. We used high sensitivity mapping of the methylated cytosine, Northern blot analysis and immunocytochemical staining in six colorectal cancer cell lines (DLD-1, SW480, Colo320, HT29, WiDr, and Colo201) to examine the relationship between the methylation status of the CpG loci in the 5'-flanking region of the APC gene and its expression. APC mRNA expression levels determined by Northern blot analysis correlated well with APC protein levels visualized by immunocytochemistry. In these colorectal cancer cell lines, no major genetic alterations of the APC gene, such as amplification or deletion, were detected. Analysis of the epigenetic control of APC gene expression in these lines revealed that methylation of the CpG loci in the 5'-untranslated region of APC mRNA repressed steady-state expression of the gene. Furthermore, epigenetic alteration of the APC gene was independent of the APC protein truncation and CpG methylation of the hMLH1 promoter. Although less eminent than protein truncation by point mutation within the coding region of the APC gene, epigenetic alteration suppressing APC gene expression may significantly contribute to oncogenesis and the progression of colorectal cancer. (C) 2001 Wiley-Liss, Inc.
  • Y Sakamoto, R Kitazawa, S Maeda, S Kitazawa
    JOURNAL OF CELLULAR BIOCHEMISTRY 80 3 415 - 423 2001年 [有り][無し]
     研究論文(学術雑誌) 
    The APC genetic locus has been linked to the tumorigenesis and progression of colorectal cancer, although the precise mechanism of its involvement in this disease remains unknown. We used high sensitivity mapping of the methylated cytosine, Northern blot analysis and immunocytochemical staining in six colorectal cancer cell lines (DLD-1, SW480, Colo320, HT29, WiDr, and Colo201) to examine the relationship between the methylation status of the CpG loci in the 5'-flanking region of the APC gene and its expression. APC mRNA expression levels determined by Northern blot analysis correlated well with APC protein levels visualized by immunocytochemistry. In these colorectal cancer cell lines, no major genetic alterations of the APC gene, such as amplification or deletion, were detected. Analysis of the epigenetic control of APC gene expression in these lines revealed that methylation of the CpG loci in the 5'-untranslated region of APC mRNA repressed steady-state expression of the gene. Furthermore, epigenetic alteration of the APC gene was independent of the APC protein truncation and CpG methylation of the hMLH1 promoter. Although less eminent than protein truncation by point mutation within the coding region of the APC gene, epigenetic alteration suppressing APC gene expression may significantly contribute to oncogenesis and the progression of colorectal cancer. (C) 2001 Wiley-Liss, Inc.
  • R Kitazawa, S Kitazawa
    ACTA HISTOCHEMICA ET CYTOCHEMICA 34 5 321 - 328 2001年 [有り][無し]
     研究論文(学術雑誌) 
    Fracture repair is a sequence of events involving formation of hematoma, recruitment of mesenchymal cells, induction of cartilaginous and bony callus, and remodeling of woven bone tissues. Decalcified tissues of mouse fracture model were subjected to in situ hybridization with PCR-derived single-stranded DNA probes. Bone morphogenetic protein (BMP)-2 transcripts were detected primarily in mesenchymal cells at the fracture site. Strong signals for BMP-2 and -3 and moderate signals for BMP-4 and -6 were detected in chondrocytes of the cartilaginous callus (days 7-10) and in osteoblasts of the bony callus (days 10-14), where transcripts of Runx2/Cbfa1 (an osteoblastic transcription factor downstream of BMP) were detected in chondrocytes and osteoblasts. BMP signals finally decreased 21 days after the fracture. Since immature cells expressing BMPs differentiated into chondrocytes or osteoblasts, BMPs might promote fracture healing through paracrine and autocrine mechanisms. During fracture healing, on the other hand, a number of osteoclasts were involved in the resorption of cartilaginous and bony callus; receptor activator of NF-kB ligand (RANKL), recently identified as a requisite to osteoclastogenesis, was expressed on mesenchymal cells (day 4) as well as on osteoblasts (days 10-21). Since Runx2/Cbfa1 binding sites are found on the mouse RANKL gene promoter, RANKL expression and osteoclastogenesis could also be promoted through Runx2/Cbfal at the phase of accelerated bone formation during fracture healing.
  • McHugh K.P, Kitazawa S, Teitelbaum S.L, Patrick Ross F
    Journal of Cellular Biochemistry 81 2 320 - 332 2001年 [有り][無し]
     研究論文(学術雑誌) 
    Expression of the alpha (v)beta3 integrin by murine bone marrow macrophages is regulated by cytokines such as IL-4 and GM-CSF through transcriptional activation of the beta (3) subunit gene. To characterize the molecular mechanisms by which such regulation occurs, we isolated the murine beta (3) integrin promoter. To this end, we first cloned a full length beta (3) cDNA and used the 5 ' UTR and leader peptide coding sequence to identify genomic clones containing the beta (3) promoter region. The transcriptional start site, identified by primer extension and S1 nuclease assay, is 34 nt upstream of the translation initiation codon. A 1.1 kb fragment of the promoter region drives IL-4 responsive transcription in transiently transfected murine bone marrow macrophages. Deletion analysis of the beta (3) promoter indicates the IL-4 responsive element lies between -465 to --678 nt relative to the transcriptional start site. This promoter fragment contains two overlapping STAT consensus recognition sites and nuclear extracts from BMMs contain an IL-4-inducible DNA binding factor, identified by super shift analysis, as STAT-6. Furthermore, an oligonucleotide which includes the two STAT recognition sites residing in the IL-4 responsive region of the beta (3) promoter, competes for STAT-6 binding. Confirming IL-4 induction of the integrin subunit is specifically mediated by STAT-6, beta (3) mRNA is not enhanced in BMMs derived from STAT-6 deleted mice, which however, retain their capacity to respond to CM-CSF. (C) 2001 Wiley-Liss, Inc.
  • T Fujimoto, R Kitazawa, S Maeda, K Mizuno, S Kitazawa
    ACTA HISTOCHEMICA ET CYTOCHEMICA 34 1 1 - 7 2001年 [有り][無し]
     研究論文(学術雑誌) 
    Bone morphogenetic protein (BMP)-3/osteogenin has a diverse spectrum of biological functions ranging from bone induction to developmental organogenesis. To clarify the role of BMP-3 during bone formation and maintenance, we investigated the expression of BMP-3 mRNA by in situ hybridization (ISH) on 4% paraformaldehyde fixed decalcified bone of normal and fractured bone of adult mice and in the whole body of the mouse fetus with digoxigenin-labeled single-stranded DNA probes generated by PCR. Our modified in situ hybridization technique at the electron microscopic level was also applied to identify specific cell types expressing BMP-3 during endochondral ossification in the developing fetal bone. Besides its expression in the developing fetal bronchial epithelium and glial cells of the brain, BMP-3 expression was observed mainly on chondrocytic cells during maturation in the normal growth plate and the fractured callus of the adult long bone and the developing fetal woven bone, suggesting that BMP-3 expression was related not to differentiation of mesenchymal cells into the chondrocytic cell lineage but to the differentiation of immature chondrocytic cells into more mature chondrocytes.
  • L Riggs, R Baron, WJ Boyle, M Drezner, S Manolagas, TJ Martin, AF Stewart, T Suda, H Yasuda, J Aubin, D Goltzman
    BONE 27 6 761 - 764 2000年12月 [有り][無し]
     研究論文(学術雑誌) 
    Recently, three new family members of the tumor necrosis factor (TNF) ligand and receptor signaling system that play a critical role in the regulation of bone resorption have been identified and cloned. These also have been shown to play an important role in regulating the immune system. A proliferation of synonyms for these molecules has led to miscommunication and redundancy. To resolve this, the President of the American Society for Bone and Mineral Research (ASBMR) appointed a special committee to recommend a standard nomenclature. After considerable deliberation and after vetting by workers in the field, the Committee recommends the names of receptor activator of NF-kappaB (RANKL) for the membrane receptor, RANK ligand (RANK) for the ligand, and osteoprotegerin (OPG) for the decoy receptor. (C) 2000 by Elsevier Inc. & the American Society for Bone and Mineral Research. All rights reserved.
  • K Takeuchi, K Murata, K Funaki, S Kitazawa, R Kitazawa
    GYNECOLOGIC ONCOLOGY 79 3 504 - 507 2000年12月 [有り][無し]
     研究論文(学術雑誌) 
    Background Humoral hypercalcemia of malignancy is a cancer-related hypercalcemia caused by the production of humoral factors by malignant cells in patients without bone metastases. Squamous cell carcinomas are the tumors most frequently associated with humoral hypercalcemia of malignancy, and parathyroid hormone-related protein (PTH-rP) is the main humoral factor implicated. Squamous cell carcinoma arising from mature cystic teratoma is a rare diagnosis itself, much less the description of associated hypercalcemia, despite the fact that the normal keratinocytes produce parathyroid hormone-related protein. Case We present a well-documented case of squamous cell carcinoma arising from mature cystic teratoma of the ovary, complicated by hypercalcemia in a patient with high levels of plasma parathyroid hormone-related protein and immunohistochemical evidence of parathyroid hormone-related protein expression by the tumor cells. Conclusion, in this case, the carcinoma cells had already produced PTH-rP in the primary tumor although the serum calcium levels had not been significantly high at surgery. It is therefore suggested that hypercalcemia may have occurred after PTH-rP production had overcome the homeostatic level during the terminal stage. (C) 2000 Academic Press.
  • N Katayama, S Murao, T Ajiki, S Kitazawa, H Onoyama, Y Kuroda, S Maeda
    INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 6 5 539 - 542 2000年11月 [有り][無し]
     研究論文(学術雑誌) 
    S100A4, one of the tandemly arranged S100 genes at chromosome 1q21, has been suggested to play a functional role in cell motility and invasiveness of tumor cell growth. We investigated the expression of S100A4 and the in vitro invasiveness of 4 human bile duct adenocarcinoma cell lines by the Matrigel assay. S100A4 was abundantly expressed in 2 adenocarcinoma cell lines whose growth pattern was highly invasive. Induction of antisense S100A4 into one of the cell lines decreased S100A4 mRNA levels and reduced invasiveness. In contrast, induction of sense S100A4 expression into non-invasive KMBC adenocarcinoma cells, which originally lacked S100A4 expression, resulted in apparent invasive potential in the transfected cells compared with the cells with the vector alone. These results suggest that S100A4 expression is well correlated with the invasiveness of human bile duct adenocarcinomas.
  • S Niemhom, S Kitazawa, S Murao, S Kunachak, S Maeda
    CANCER LETTERS 160 2 199 - 208 2000年11月 [有り][無し]
     研究論文(学術雑誌) 
    Epstein-Barr virus (EBV! has been well documented in the aetiology of nasopharyngeal carcinoma (NPC), although its role as well as the genetic basis in the genesis of NPC have not been elucidated, The p53 gene mutations are infrequently found in NPC, but the expression of p53 protein, as well as bcl-2. oncoprotein, has been reported in a high percentage of cases, and also in association with EBV. Proliferating cell nuclear antigen (PCNA) has also been shown to be increased in NPC, suggesting its association among the overexpression of p53 and bcl-2 oncoprotein. We undertook this study to evaluate the correlation among these abnormalities in the development of NPC. The expression of p53 protein, bcl-2 oncoprotein, and the level of PCNA were investigated by immunohistochemistry in 53 patients with NPC. Twenty tissue samples from these patients were studied for p53 ene mutations by single strand conformation polymorphism (SSCP) and DNA sequencing as well as EBV genomes by polymerase chain reaction, Among the 53 specimens, 42 (79%) showed expression of p53 protein and 40 (75%) gave positive result for bcl-2 oncoprotein. A significant association was found between p53 expression and bcl-2 oncoprotein (P = 0.002; Fisher's exact test) with 68% of the patients showing coexpression of both markers. The PCNA labelling index in the 53 patients varied from 5% to 80%. High PCNA labelling index was frequently feued in the patients with overexpression of p53 protein and bcl-2 oncoprotein. The PCNA index in patients wi th p53 expression was significant higher th an in those without p53 expression (P = 0.002). Of the 20 patients, p53 mutations were found in four cases. EBV genomes were detected in 14 cases of which 12 cases showed overexpression of both p53 and bcl-2 and one case with only p53 expression and one case with bcl-2 expression. EBV genomes were detected in two cases with p53 mutations. We conclude that EBV is the important etiologic factor in NPC which may be involved in p53 and bcl-2 overexpression. The mutant p53 protein is correlated to deregulation of PCNA. p53 mutations participate in a small proportion of the tumorigenesis. (C) 2000 Elsevier Science ireland Ltd. All rights reserved.
  • S Yano, T Sugimoto, T Tsukamoto, K Chihara, A Kobayashi, S Kitazawa, S Maeda, R Kitazawa
    KIDNEY INTERNATIONAL 58 5 1980 - 1986 2000年11月 [有り][無し]
     研究論文(学術雑誌) 
    Background The down-regulation of both calcium-sensing receptor (CaSR) and vitamin D receptor (VDR) in parathyroid (PT) glands of secondary hyperparathyroidism (HPT) caused by chronic renal failure has been associated with PT hormone hypersecretion as well as PT hypergrowth. To clarify the predominance of decreased expression of CaSR and VDR in the high proliferative activity of PT glands, we examined the relationship between the expression of both receptors and proliferative activity in human PT glands. Methods. Serial sections of 56 PT glands, including 52 glands from secondary HPT and 4 normal PT glands resected together with thyroid carcinoma, were examined immunohistochemically with specific antibodies against CaSR, VDR, and Ki67. The Ki67-positive cell number was counted and expressed as the Ki67 score. The CaSR and VDR expressions were semiquantitatively analyzed. Results. The expressions of both CaSR and VDR were markedly decreased in PT glands of secondary HPT, while the Ki67 score was significantly higher than it was in normal controls. When hyperplastic glands were classified into two subgroups, with [N(+)] or without [N(-)] nodular formation, CaSR expression was significantly decreased in N(+), while VDR expression was not different. Multiple regression analyses revealed that the decreased expression of CaSR could contribute significantly to the high proliferative activity, even if VDR expression was taken into account. Conclusion. The decrease in CaSR expression is associated with the high proliferative activity of PT glands in secondary HPT, independently of the decreased VDR expression. These findings provide a new insight into the pathogenesis of PT hyperplasia, which is refractory to vitamin D therapy in patients with severe secondary HPT.
  • K Gohji, M Nomi, Y Niitani, S Kitazawa, A Fujii, Y Katsuoka, M Nakajima
    JOURNAL OF CLINICAL ONCOLOGY 18 16 2963 - 2971 2000年08月 [有り][無し]
     研究論文(学術雑誌) 
    Purpose: We retrospectively investigated whether the level of serum hepatocyte growth factor could predict the prognosis and extent of transitional-cell carcinoma of the urinary bladder. Patients and Methods; Serum samples were collected from 113 patients with bladder cancer and from 200 healthy controls. Of the 113 patients, 59 had superficial bladder cancer and 54 had muscle-invasive cancer. Thirteen bladder cancer tissues (eight superficial and five muscle-invasive) were also collected. The levels of hepatocyte growth factor in the serum and tissues of these individuals were measured by enzyme-linked immunoadsorbent assay using hepatocyte growth factor antibodies. Results: The levels of hepatocyte growth factor in the serum and tissues of patients with muscle-inversive cancer were significantly higher than those of patients with superficial bladder cancer (P < .0001 and P = .0054, respectively). The degree of elevation above the normal level of serum hepatocyte growth factor of the former (61.1%) was significantly higher than that of the latter (8.4%; P < .0001). The elevation wets highest in patients with visceral metastasis (93.3%). Among patients with superficial bladder cancer, the overall survival rate of those with low levels of serum hepatocyte growth factor was significantly greater than that of those with high levels (P = .005). Among patients with minimally invasive bladder cancer, the disease-free and overall survival rates of those with high levels of serum hepatocyte growth factor were significantly lower than the same rates of those with low levels (P < .001 and P = .0028, respectively). Conclusion: Our study suggests that the level of hepatocyte growth factor in serum could be a predictor of patient survival and extent of bladder cancer. (C) 2000 by American Society of Clinical Oncology.
  • S Inamoto, S Murao, M Yokoyama, S Kitazawa, S Maeda
    PATHOLOGY INTERNATIONAL 50 6 480 - 485 2000年06月 [有り][無し]
     研究論文(学術雑誌) 
    S-100 proteins (S100) are characterized by calcium-binding ability with two structural EF hands. Several S100 are expressed in cardiomyocytes and thought to play a crucial role in calcium signaling. To examine whether the expression of S100 is a response to detectable myocardial damage or regeneration, we investigated, immunohistochemically, the expression of S100A4 and S100A11 in the isoproterenol (ISP)-treated rat heart. Definite expression of S100A4 and S100A11 was demonstrated in normal cardiomyocytes, and their staining patterns were enhanced in the ISP-treated rat heart, suggesting the possible involvement of S1-A4 and S100A11 in ISP-induced myocardial damage.
  • Nakayama, I, S Murao, S Kitazawa, A Azumi, M Yamamoto, S Maeda
    PATHOLOGY INTERNATIONAL 50 3 191 - 199 2000年03月 [有り][無し]
     研究論文(学術雑誌) 
    The TCL1 gene, localized near the break point of chromosome 14q32.1 often involved in T cell leukemias, is also expressed in normal precursor T and B cells, and B cell lymphoma cell lines. We investigated the expression of the TCL1 protein in various types of B cell lymphomas according to the Revised European-American Classification of Lymphoid neoplasms, Paraffin-embedded tissue sections of lymphoma specimens were subjected to TCL1 immunohistochemistry, and positivity was scored on a three-tiered scale: - (< 25% cells), + (25-50% cells), and ++ (> 50% cells). The TCL1 protein was expressed in low-grade B cell lymphomas including mucosa-associated lymphoid tissue type in ocular adnexa (18/20, 90%), It was also expressed in follicular, lymphoplasmacytic, and mantle cell lymphoma, but not in high-grade diffuse large B cell lymphoma (2/11, 18%). These data suggest that the expression of the TCL1 gene characterizes low-grade B cell lymphomas, and may be involved in certain processes of lymphomatogenesis.
  • M Uozumi, S Murao, N Katayama, S Kitazawa, M Amatsu, S Maeda
    CANCER LETTERS 149 1-2 135 - 141 2000年02月 [有り][無し]
     研究論文(学術雑誌) 
    S100A4 is considered functionally involved in metastasis and invasiveness of rodent and human mammary tumors. We screened the expression of S100A4 in human squamous cell carcinoma cell lines, and found 2 cell lines which were highly invasive, but did not express any noticeable extent of S100A4. To examine whether the expression of S100A4 regulated invasiveness of squamous cell carcinoma, we transfected S100A4 cDNA into KOCS-3 and HSC-4 squamous cell carcinoma cells. The transfectants from KOSC-3 cells expressing sense S100A4 decreased invasiveness by 80% compared with cells of the wild type or those with the vector only. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.
  • S Kitazawa, R Kitazawa, S Maeda
    LABORATORY INVESTIGATION 80 2 275 - 276 2000年02月 [有り][無し]
     研究論文(学術雑誌)
  • Gohji K, Katsuoka Y, Okamoto M, Kamidono S, Kitazawa S, Toyoshima M, Dong J, Nakajima M
    Hinyokika Kiyo 46 10 757 - 62 2000年 [有り][無し]
  • Kohno N, Kitazawa S
    Nippon Rinsho 58 Suppl 345 - 51 2000年 [有り][無し]
  • Ryu Y, Tani S, Hagihara R, Kachi M, Maeda M, Yagi N, Morita M, Yamashita J, Shinkai M, Ikegawa R, Imanishi K, Hirata Y, Kitazawa S
    Nippon Shokakibyo Gakkai Zasshi 97 11 1401 - 3 2000年 [有り][無し]
  • K Takeuchi, K Murata, K Funaki, Fujita, I, Y Hayakawa, S Kitazawa
    EUROPEAN JOURNAL OF GYNAECOLOGICAL ONCOLOGY 21 3 290 - 291 2000年 [有り][無し]
     研究論文(学術雑誌) 
    A case of primary liposarcoma of the cervix is described in a 49-year-old woman with a fungating cervical mass which was diagnosed as liposarcoma on the basis of cytologic features and the intracellular lipids. Most of the adipocytes and vacuolated lipoblasts were positive for S-100 protein. The mass was well circumscribed and limited to the superficial cervical stroma. A total abdominal hysterectomy and bilateral salpingo-oophorectomy with pelvic lymphadenectomy was performed. There was no clinical evidence of metastasis two years after the operation.
  • Gohji K, Katsuoka Y, Okamoto M, Kamidono S, Kitazawa S, Toyoshima M, Dong J, Nakajima M
    Acta Urologica Japonica 46 10 757 - 762 2000年 [有り][無し]
  • Kohno N, Kitazawa S
    Nippon rinsho. Japanese journal of clinical medicine 58 Suppl 345 - 351 2000年 [有り][無し]
  • H Ueno, R Yoneda, W Ogawa, S Yoon, S Kitazawa, R Kitazawa, M Kasuga
    ACTA HAEMATOLOGICA 104 4 212 - 216 2000年 [有り][無し]
     研究論文(学術雑誌) 
    A 59-year-old man with progressive and advanced agnogenic myeloid metaplasia, also called idiopathic my elofibrosis, had complications showing bilateral interstitial pneumonic shadows. Pathological assessment of transbronchial biopsy revealed pulmonary perivascular fibrosis and infiltration of megakaryocytes. Autopsy 3 months later showed extramedullary megakaryopoiesis and fibrosis in lung, pleura, kidney, liver and spleen. Histopathological analysis for platelet-derived growth factor (PDGF) and PDGF-receptor revealed an abnormally high expression of the PDGF-receptor-beta gene in pulmonary fibroblasts. This is the first description of an association between pulmonary fibrosis and PDGF in idiopathic myelofibrosis. Copyright (C) 2001 S. Karger AG, Basel.
  • S Kitazawa, R Kitazawa, S Maeda
    JOURNAL OF BIOLOGICAL CHEMISTRY 274 40 28787 - 28793 1999年10月 [有り][無し]
     研究論文(学術雑誌) 
    Cyclin D1, a G(1)/S cell cycle-regulating oncogene, is known to be transcriptionally regulated by numerous growth factors. We cloned and characterized the rat cyclin D1 gene 5'-flanking region and, by species- and subspecies-matched transient transfection studies, found that a basic promoter structure with a cAMP response element and two continuous Spl-binding sites was crucial for the steady-state expression of the cyclin D1 gene. Furthermore, the methylation status especially around two continuous Spl-binding sites was found to be an important epigenetical mechanism determining the steady-state expression level in rat leukemic cell lines K4D, K4DT, and K4D16. Whether or not epigenetic control of the cyclin D1 gene existed among normal rat tissues was further examined by high sensitivity mapping of the methylated cytosine, In normal rat tissues, the methylated cytosines at non-CpG loci within two continuous Spl-binding sites were observed in uterine stromal cells of the basal layer and found to be demethylated in the functioning layer, possibly by a passive demethylation mechanism through cell division. Since in the passive demethylation process Spl-binding sites remain methylated in a part of the cell population, methylated cytosines at Spl-binding sites may be essential for keeping a number of the stromal cells in the basal layer live against estrogen-induced proliferation that leads to either apoptosis or compaction.
  • R Kitazawa, S Kitazawa, S Yoon, M Kasuga, S Maeda
    VIRCHOWS ARCHIV-AN INTERNATIONAL JOURNAL OF PATHOLOGY 435 2 137 - 142 1999年08月 [有り][無し]
     研究論文(学術雑誌) 
    A 69-year-old man had a hepatic tumour occupying the left and half of the right lobe, with portal vein thrombus. There were hypercalcaemia and hypophosphataemia with increased nephrogenous cyclic adenosine monophosphate; bone metastases were excluded. Serum parathyroid hormone-related protein (PTHrP) was elevated, but no increase in intact parathyroid hormone (PTH) or vitamin Dg metabolites was found. At autopsy the histological features were typical of sclerosing hepatic carcinoma. By immunohistochemistry PTHrP was detected in cancer cell nests but not in the fibrous stroma. PTHrP transcripts were demonstrated by in situ hybridization using a polymerase chain reaction (PCR)-derived single-stranded DNA probe. Tumour cells expressed AE1 and CA19-9 (markers for cholangioepithelium) and CEA (for bile canaliculi). Electron microscopy revealed microvilli on the apical surface, and secretory granules 100 nm in diameter were observed. These findings indicate that this case is one of cholangiocellular sclerosing hepatic carcinoma. The interaction between cancer and stromal cells may be the cause of PTHrP overexpression.
  • Fujii H, Kitazawa R, Maeda S, Mizuno K, Kitazawa S
    Histochemistry and Cell Biology 112 2 131 - 138 1999年08月 [有り][無し]
     研究論文(学術雑誌) 
    Platelet-derived growth factor (PDGF), abundant in bone tissue, has been reported to stimulate mesenchymal cell proliferation and migration. To elucidate the functional roles of PDGF during fracture healing, we investigated the expression of PDGF-A and -B chain proteins and receptor ex and beta mRNAs in fractured mouse tibiae. Twelve-week-old male BALB/c mice were operated on to make a closed fracture on the proximal tibia. On days 2, 4, 7, 10, 14, 21, and 28 after the operation, the fractured tibiae were excised, fixed with 4% paraformaldehyde, decalcified with 20% EDTA, and embedded in paraffin to prepare 7-mu m sections. Immunohistochemistry using polyclonal antibodies against human PDGF-A and B chains was carried out by the avidin-biotin-peroxidase method. For in situ hybridization, we used digoxigenin-labeled single-stranded DNA probes specific for mouse PDGF receptors alpha and beta generated by unidirectional polymerase chain reaction. In the inflammatory phase on days 2-4 after the fracture, mesenchymal cells gathering at the fracture site expressed the PDGF-B chain and beta receptor mRNA. At the stage of cartilaginous callus formation on day 7, the immunoreactivity for PDGF-A and -B chains on proliferating and hypertrophic chondrocytes and the signals of alpha and beta receptor mRNAs on proliferating chondrocytes became manifest. At the stage of bony callus and bone remodeling on days 14-21, the predominant expression of the PDGF-B chain and beta receptor was observed on both osteoclasts and osteoblasts. On day 28, signals for PDGF ligand proteins and receptor mRNAs diminished. The coincidental localization of PDGF ligands and their receptors implies a paracrine and autocrine mechanism. Our data suggested that PDGF contributed in part to the promotion of the chondrogenic and osteogenic changes of mesenchymal cells from the early to the midphase of fracture healing; the functions mediated by the beta receptor including cell migration, might be prerequisites to the recruitment of mesenchymal cells in the initial step and to the interaction between osteoclasts and osteoblasts in the bone remodeling phase.
  • Y Zhou, H Kato, D Shan, R Minami, S Kitazawa, T Matsuda, T Arima, JC Barrett, N Wake
    MOLECULAR CARCINOGENESIS 25 1 64 - 72 1999年05月 [有り][無し]
     研究論文(学術雑誌) 
    To define the target of chromosome 18q loss of heterozygosity, which is prevalent in endometrial carcinomas, we made a deletion map from 64 tumors. Loss of heterozygosity on 18q was found in 20 tumors. Among these, 14 tumors carried deletions at the 18q21.1 region, where the DPC4 gene is located. DPC4 transcription was disturbed in all six of the tumors with deletions at 18q21.1 examined, which sharply contrasted with the positive transcription in 12 tumors that retained heterozygosity at the 18q21.1 region. However, in the 14 tumors with the 18q21.1 deletions, the remaining allele had the wild-type sequence of the DPC4 coding region instead of somatic mutations in the DPC4 coding region. We found a one- and two-base substitutions in the DPC4 promoter in two of the six tumors that showed disturbed DPC4 transcription. Chloramphenicol acetyltransferase assays clearly demonstrated that the mutant promoters had the potential to suppress or silence DPC4 transcription, implicating the DPC4 gene in endometrial carcinoma. (C) 1999 Wiley-Liss, Inc.
  • R Kitazawa, S Kitazawa, S Maeda
    BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION 1445 1 134 - 141 1999年04月 [有り][無し]
     研究論文(学術雑誌) 
    Receptor activator of NF-kappa B ligand (RANKL)/tumor necrosis factor-related activation induced cytokine (TRANCE)/osteoprotegerin ligand (OPGL)/osteoclast differentiation factor (ODF) is a membrane-bound signal transducer responsible for differentiation and maintenance of osteoclasts. To elucidate the mechanism regulating RANKL/TRANCE/OPGL/ODF gene expression, we cloned the 5'-flanking basic promoter region of the mouse RANKL/TRANCE/OPGL/ODF gene and characterized it by transient transfection studies and genomic Southern blot analysis. Inverted TATA- and CAAT-boxes and a putative Cbfal/Osf2/AML3 binding domain constituted the basic promoter structure. The repeated half-sites for the vitamin D-3 (VitD(3)) and glucocorticoid receptors were located at -935 and -640, respectively. Transient transfection studies revealed that short-term treatment with 1 alpha,25(OH)(2) VitD(3) or dexamethasone increased luciferase activity up to 204% and 178%, respectively; on the other hand, treatment with dibutyryl cyclic AMP did not affect the promoter activity. Since the expression of Cbfa1/Osf2/AML3 is also regulated by VitD(3), 1 alpha,25(OH)(2) VitD(3) might affect RANKL/TRANCE/OPGL/ODF gene expression both directly and indirectly. CpG methylation was observed dominantly in mouse stromal cells, ST2, of a later passage which ceased to support in vitro osteoclastogenesis, suggesting that the methylation status of the CpG loci in the RANKL/TRANCE/OPGL/ODF gene promoter may be one of the influential cis-regulating factors. (C) 1999 Elsevier Science B.V. All rights reserved.
  • Furukawa K, Tani S, Fukuda M, Nishizawa A, Sakai M, Morita M, Imanishi K, Yamashita J, Kitazawa S, Oimomi M
    Nippon Shokakibyo Gakkai Zasshi 96 2 160 - 3 1999年 [有り][無し]
  • Tani S, Furukawa K, Fukuda M, Maeda M, Sakai M, Morita M, Yamashita J, Kitazawa S, Oimomi M
    Nippon Shokakibyo Gakkai Zasshi 96 5 540 - 4 1999年 [有り][無し]
  • Kohno N, Kitazawa S, Konishi M, Wakita K, Furuya Y, Kawaguti K
    Breast Cancer 6 4 292 - 297 1999年 [有り][無し]
  • S Kitazawa, R Kitazawa, S Maeda
    HISTOCHEMISTRY AND CELL BIOLOGY 111 1 7 - 12 1999年01月 [有り][無し]
     研究論文(学術雑誌) 
    A rapid and simplified protocol for in situ hybridization (ISH) with polymerase chain reaction (PCR)derived single-stranded DNA probes and S1 nuclease revealed transcripts of bone matrix proteins on decalcified skeletal bone specimens. Mouse bone tissue was fixed with 4% paraformaldehyde, decalcified with 20% EDTA, and embedded in paraffin. Each pair of primers for reverse transcriptase -PCR was designed to amplify a 280-bp DNA fragment from the coding region of the mature protein of mouse osteonectin (ON) and a 320-bp fragment from the coding region of mouse osteopontin (OP). Initial PCR products were eluted, purified, and reamplified by unidirectional PCR in the presence of the digoxigenin (DIG)-labeled dUTP. ISH was carried out by proteinase K treatment, hybridization, and washing. The unhybridized single-stranded DNA probe was selectively removed by S1 nuclease treatment. Hybridized probes were visualized with the alkaline phosphatase-conjugated anti-DIG antibody. The transcripts of ON and OP were clearly detected on the thin sections of the decalcified bone. Because this protocol does not require cloning or in vitro transcription, reliable and stable ISH can be done in an ordinary laboratory equipped with a thermal cycler.
  • S Kitazawa, R Kitazawa, H Tamada, S Maeda
    BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION 1443 3 358 - 363 1998年12月 [有り][無し]
     研究論文(学術雑誌) 
    Sonic hedgehog (Shh) is a secreted signal transducer responsible not only for patterning of the anterior-posterior axis during early limb and neuronal development, but also for generating cell-type diversity at later developmental stages. To elucidate the mechanism regulating human Shh gene expression, we cloned the 5'-flanking region of the human Shh gene and characterized it by transient transfection studies. Two transcription start sites were identified by primer extension analysis. Two TATA-boxes, a CCAAT-box and a palindrome-like structure constituted the basic promoter structure. Furthermore, two continuous E-boxes and a putative homeodomain containing an ATTA-box were located around 350-450 bp upstream of the upper TATA-box. Consensus binding sites of the RA, estrogen, D3 and glucocorticoid/progesterone receptors were not found within the cloned sequence. Short-term treatment with TPA increased luciferase activity up to 2.1-fold; on the other hand, treatment with dibutyryl-cyclic AMP decreased it to 0.8-fold. Retinoic acid (RA), vitamin D3, dexamethazone (DEX) and estradiol (E2) had no effect on the luciferase activity. Since the zebrafish Shh promoter contains two closely spaced axial (HNF3 beta) binding sequences on its basic promoter, the palindrome-like structure located in the corresponding site of the human Shh promoter may be a crucial binding domain regulating human Shh gene expression. (C) 1998 Elsevier Science B.V. All rights reserved.
  • R Minami, R Kitazawa, S Maeda, S Kitazawa
    BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION 1443 1-2 182 - 185 1998年11月 [有り][無し]
     研究論文(学術雑誌) 
    Among the transducers of the transforming growth factor (TGF)-beta/bone morphogenetic protein (BMP) receptor signaling proteins, Smad4 and Smad1 act together in BMP 2/4 signaling pathways, and Smad4 and Smad2 act in TGF-beta/activin signaling. To investigate how the Smad it gene is regulated at the transcriptional level, we cloned and characterized its 5'-flanking region. The major transcription start site mapped by primer extension analysis was 132 bp upstream of the translation start site. The promoter region lacked canonical TATA and GC boxes; it did, however, contain a TATA-like structure (TAAAAT) 32 bp upstream of the transcription start site. A consensus sequence for homeoprotein HoxA-5 (TTTAAAAATTA) was identified at 171 bp upstream of the transcription start site. Within 600 bp upstream of the transcription start site, two Pit-1 and four F2F binding sites were found. One putative AP-I site was located at -1129. These findings suggest that these homeoproteins could conduct their signals specifically by controlling both inter- and intracellular signal transduction pathways. (C) 1998 Elsevier Science B.V. All rights reserved.
  • A Muraoka, Suehiro, I, M Fujii, H Ueno, S Hayashi, K Shimizu, R Kitazawa, S Kitazawa, K Murakami
    JOURNAL OF GASTROENTEROLOGY 33 3 326 - 329 1998年06月 [有り][無し]
     研究論文(学術雑誌) 
    We report a type IIa early gastric cancer associated with xanthoma cell proliferation in a 61-year-old man. The patient was admitted to our hospital because of a gastric polyp detected at a medical checkup. An irregular protruding lesion with xanthoma cell proliferation was detected endoscopically. Histological examination showed a well differentiated tubular adenocarcinoma in the mucosa associated with xanthoma cell proliferation. The distribution of the xanthoma cells in the stroma corresponded closely with that of the cancer cells. Neither atypism nor mitotic figures were recognized in the xanthoma cells. In an immunohistochemical study, almost all the xanthoma cells were stained positive for alpha(1)-antitrypsin, while relatively few exhibited positive S-100 protein staining. Specific monocyte chemotactic and activating factor im munoreactivity was present only in the xanthoma cells, and not in the cancer cells. On the basis of these findings, it was speculated that the gastric cancer cells may have caused the xanthoma cell proliferation via an autocrine mechanism i.e., by a chemical mediator acting in a paracrine or juxtacrine manner.
  • K Gohji, N Fujimoto, Hara, I, A Fujii, A Gotoh, H Okada, S Arakawa, S Kitazawa, H Miyake, S Kamidono, M Nakajima
    INTERNATIONAL JOURNAL OF CANCER 79 1 96 - 101 1998年02月 [有り][無し]
     研究論文(学術雑誌) 
    We examined whether the serum matrix metalloproteinase-2 (MMP-2) level and MMP-2 density could be predictors of the development and extension of prostate cancer, Serum samples were collected before any clinical treatment from 98 patients with prostate cancer and from 76 patients with benign prostatic hyperplasia (BPH). Control sera were obtained from 70 healthy men, The serum level of MMP-2 was determined by 1-step enzyme immunoassay. A newly defined MMP-2. density parameter was determined by dividing the serum level of MMP-2 by the prostate volume, which was measured by ultrasonography, The mean serum level of MMP-2, in prostate cancer patients was significantly higher than in the control and BPH groups, Furthermore, the serum MMP-2 levels in prostate cancer patients with metastasis were highly elevated compared with those without metastases, The MMP-2 density in pathologically organ-confined prostate cancer was significantly higher than that in BPH. There was a statistically significant difference in the MMP-2 density between pT2N0M0 and pTIN0M0 prostate cancers, Moreover, the serum MMP-2 Bevel correlated well with the clinical course of prostate cancer with bone metastasis. Our results suggest that MMP-2 plays an important role in the development and extension of prostate cancer and that the serum level of MMP-2 and the MMP-2 density indicate prostate cancer extension and are, therefore, useful for the followup of prostate cancer patients. (C) 1998 Wiley-Liss, Inc.
  • H Tamada, R Kitazawa, K Gohji, S Kamidono, S Maeda, S Kitazawa
    BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION 1395 3 247 - 251 1998年02月 [有り][無し]
     研究論文(学術雑誌) 
    We cloned a genomic fragment of the 5'-flanking region of the gene encoding bone morphogenetic protein-6 (BMP-6) and assessed its promoter activity. Primer extension revealed the presence of one major transcription start site 178 bp upstream of the translation start site. The promoter region lacked a canonical TATA box but did contain a GC-rich region. A putative tramtrack responsive element, a Drosophila transcriptional factor regulating the segment polarity, was found in the promoter region. Known steroid hormonal responsive elements, however, were not found. Although BMP-6 is classified as a member of the vgr-1 family, the structure of the promoter was similar to that of BMP-2 and 4. (C) 1998 Elsevier Science B.V.
  • K Takeuchi, S Kitazawa, S Kitagaki, T Maruo
    INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS 60 2 151 - 154 1998年02月 [有り][無し]
     研究論文(学術雑誌) 
    Objective: To describe the usefulness of fine-needle aspiration cytology and drainage, followed by long-acting GnRH-agonist therapy in the management of post-operative peritoneal cysts with endometriosis. Methods: In six women who were diagnosed as having post-operative peritoneal cysts with endometriosis, fine-needle aspiration cytology and drainage was performed. Thereafter, four patients were treated with long-acting GnRH-agonists for 6 months. Two patients refused the treatment. Results: In all patients fine-needle aspiration yielded specimens which consisted of a population of mesothelial cells. The mean follow-up time was 4 years (range 3.5 - 5). The four patients treated with long-acting GnRH-agonists show no evidence of recurrence. In two patients who had no additional treatment, the recurrence of the cyst was noted 2 months and 5 months after the drainage. Conclusion: Combination of fine-needle aspiration cytology and drainage and subsequent long-acting GnRH-agonist therapy can be a useful conservative management of post-operative peritoneal cysts associated with endometriosis. (C) 1998 International Federation of Gynecology and Obstetrics.
  • Tani S, Furukawa K, Fukuda M, Nishizawa A, Sakai M, Morita M, Kitazawa S, Oimomi M
    Nippon Shokakibyo Gakkai Zasshi 95 12 1357 - 61 1998年 [有り][無し]
  • Mitsutsuji M, Kitazawa R, Tamada H, Maeda S, Kitazawa S
    Journal of Biochemistry, Molecular Biology and Biophysics 2 1 59 - 63 1998年 [有り][無し]
  • H Kashimoto, R Kitazawa, S Maeda, K Mizuno, S Kitazawa
    ACTA HISTOCHEMICA ET CYTOCHEMICA 31 6 501 - 508 1998年 [有り][無し]
     研究論文(学術雑誌) 
    We investigated the expression of osteonectin and osteopontin during fracture healing of mouse tibiae by in situ hybridization (ISH) and the effects of fibrin(ogen) on the expression of bone matrix proteins by Northern blot analysis. Twelve-week-old male BALB/c mice were operated on to make a closed fracture on the proximal tibiae. On days 2, 4, 7 and 14 after the operation, the fractured bones were excised, fixed with 4% paraformaldehyde (PFA) and decalcified with 20% EDTA to prepare 5-mu m sections. Digoxigenin (DIG) labeled single-stranded DNA probes generated by uni-directional polymerase chain reaction (PCR) were used for ISH. Immunohistochemistry revealed fibrin(ogen) at the site of fracture hematoma 2-4 days after fracture and subsequent accumulation of mesenchymal cells. On days 4-14 after the fracture, osteonectin signals were predominantly expressed in proliferating chondrocytes at the endochondral ossification site and in osteoblasts of the marginal woven bone. Osteopontin was expressed on osteoblasts lining the surface of the marginal woven bone at the mid-late phase of fracture healing. In vitro, Northern blot analysis showed that treatment of the mesenchymal cells, C3H10T1/2, with fibrin(ogen) enhanced the steady-state level of osteonectin and osteopontin gene expression. These data suggested that fibrin(ogen) in the hematoma may be important for inducing bone matrix genes in immature mesenchymal cells at the early phase of fracture repair.
  • R Kitazawa, S Kitazawa, H Kashimoto, S Maeda
    ACTA HISTOCHEMICA ET CYTOCHEMICA 31 3 231 - 236 1998年 [有り][無し]
     研究論文(学術雑誌) 
    We investigated the expression of bone morphogenetic protein (BMP)-2, -4 and -6 during fracture healing of mouse tibiae by in situ hybridization (ISH). Twelve-week-old male BALB/c mice were operated on to make a closed fracture on the proximal tibiae. On days 4, 7 and 14 after the operation, the fractured bones were excised, fixed with 4% PFA and decalcified with 20% EDTA to prepare 5-mu m sections. For ISH we employed digoxigenin (DIG) labeled single-stranded DNA probes specific to BMP-2, -4 and -6 generated by uni-directional polymerase chain reaction (PCR) with antisense primer alone. On days 4-14 after fracture, BMP-2 signals were predominantly expressed in proliferating-hypertrophic chondrocytes and in osteoblasts on the surface of the marginal woven bone. Weak expression of BMP-4 and -6 was detected in spindle-shaped mesenchymal cells and at the site of chondrocytic differentiation; it then decreased during the formation of woven bone. These data suggested that BMP-4 and -6 may be important in the early phase; BMP-2 contributed mainly in the mid to later phase of bone fracture repair. BMPs seemed to promote both proliferation and differentiation of mesenchymal cells through the paracrine/autocrine mechanism.
  • K Gohji, M Nakajima, D Boyd, CPN Dinney, CD Bucana, S Kitazana, S Kamidono, IJ Fidler
    AMERICAN JOURNAL OF PATHOLOGY 151 6 1655 - 1661 1997年12月 [有り][無し]
     研究論文(学術雑誌) 
    We examined the role of urokinase-type plasminogen activator (u-PA) in the metastasis of the human renal cell carcinoma (HRCC) implanted in athymic nude mice. Cells from a HRCC KG-2 line were implanted in orthotopic (kidney) and ectopic (subcutaneous) organs. The KG-2 cells implanted in the kidney produced local tumors and lung metastases, whereas those implanted subcutaneously produced only local tumors. The production of u-PA was determined by immunohistochemistry and an enzyme-linked immunosorbent assay (ELISA). High levels of u-PA were produced by the metastatic kidney tumors and lung metastases, whereas the subcutaneous tumors produced low levels. KG-2 cells co-cultured with mouse kidney or lung fibroblasts produced higher levels of u-PA than KG-2 cells co-cultured with mouse skin fibroblasts. Furthermore, KG-2 cells cultured with the conditioned medium from mouse kidney or lung fibroblasts produced higher levels of u-PA than KG-2 cells cultured with the conditioned medium from mouse skin fibroblasts. The results indicate that the expression of u-PA by KG-2 cells is one of the important factors that determine their metastatic potential and that the production of u-PA is influenced by the organ microenvironment, including soluble factors produced by surrounding fibroblasts.
  • Nishida K, Kitazawa R, Mizuno K, Maeda S, Kitazawa S
    Biochemical and Biophysical Research Communications 241 2 258 - 263 1997年12月 [有り][無し]
     研究論文(学術雑誌) 
    The integrin alpha 6 subunit associates with either the beta 1 or beta 4 subunit to form receptors for laminin, a major component of the basement membrane. Here, we characterized basal promoter of the human integrin alpha 6 subunit gene. The transcription start site, mapped by primer extension analysis, was 208 bp upstream of the translation start site. The promoter region lacked canonical TATA and GC boxes, but did contain a TATA-like sequence (GATAAA) 23 bp upstream of the major transcription start site. Consensus binding sites for Sp1 and the NF-kappa B complex were also present in the promoter region. A putative glucocorticoid/progesterone receptor responsive element (GRE/PRE), together with the Ap1 and c-myc binding sites located around 350-360 bp upstream of the transcription start site, represented positive regulatory sequences. Our current study showed a molecular model by which progesterone promotes tumor cell invasion through the basement membrane by up-regulating the laminin receptor. (C) 1997 Academic Press.
  • H Kudo, Y Takaishi, H Minami, T Takamoto, S Kitazawa, S Maeda, N Tamaki
    SURGICAL NEUROLOGY 48 4 374 - 381 1997年10月 [有り][無し]
     研究論文(学術雑誌) 
    BACKGROUND A purely intrasellar meningioma is extremely rare. All the intrasellar meningiomas reviewed in the literature presented with symptoms of hypopituitarism and/or visual disturbance. A case of intrasellar meningioma with a sudden onset of headache and diplopia, mimicking a pituitary apoplexy, is reported. CLINICAL PRESENTATION This 35-year-old man with a sudden onset of headache and double vision was admitted. Neuroimages suggested an intrasellar tumor. Although a pituitary adenoma was suspected from clinical symptoms, a meningioma was compatible with neuroradiologic findings. INTERVENTION Transsphenoidal and frontoorbito-zygomatic approaches were attempted for removal of the tumor. Pituitary apoplexy could not be proved at either operation. The histopathologic diagnosis of this tumor was a fibrous meningioma. CONCLUSION The meningeal ''tail sign'' on magnetic resonance images may be a key to diagnosing intrasellar meningiomas. (C) 1997 by Elsevier Science Inc.
  • R Kitazawa, S Kitazawa, T Matui, S Maeda
    HUMAN PATHOLOGY 28 3 379 - 382 1997年03月 [有り][無し]
     研究論文(学術雑誌) 
    A case of ovarian clear fell carcinoma associated with hypercalcemia is reported. A 67-year-old woman developed the lung metastasis 8 months after primary surgery. The patient manifested symptoms of humoral hypercalcemia of malignancy (HHM) during the last 3 months of her clinical course. Serum and urinary C-terminus parathyroid hormone-related protein (PTHrP) levels were remarkably high. No increase in interleukin (IL) 1 beta, tumor necrosis factor (TNF) alpha, vitamin D-3 metabolites or intact PTH was detected. Pamidronate disodium treatment was transiently suppressed her serum calcium level. The patient died despite seven courses of chemotherapy. Autopsy showed multiorgan metastases and accelerated osteoclastic bone resorption; skeletal metastasis was not detected. Immunohistochemical analysis clearly showed the localization of PTHrP at both the primary and metastatic sites. The transcripts of PTHrP at pulmonary metastatic sites were revealed by in situ hybridization and the reverse transcription polymerase chain reaction (RT-PCR) method. PTHrP was the causative factor for HHM in this case. It is therefore suggested that hypercalcemia may have occurred after PTHrP production had overcome the homeostatic level during the terminal stage, although PTHrP production continued irrespective of the patient's serum calcium level. Copyright (C) 1997 by W.B. Saunders Company.
  • Fujita M, Takahashi R, Liang P, Saya H, Ashoori F, Tachi M, Kitazawa S, Maeda S
    Leukemia 11 Suppl 3 444 - 5 1997年 [有り][無し]
  • SL Teitelbaum, H Tanaka, H Mimura, M Inoue, M Shima, A Shioi, M Chiba, S Kitazawa, FP Ross
    OSTEOPOROSIS INTERNATIONAL 7 SUPPL. 3 54 - 56 1997年 [有り][無し]
     研究論文(学術雑誌)
  • M Fujita, R Takahashi, K Kitada, R Watanabe, S Kitazawa, F Ashoori, P Liang, H Saya, T Serikawa, S Maeda
    CANCER LETTERS 112 1 47 - 55 1997年01月 [有り][無し]
     研究論文(学術雑誌) 
    An alternative splicing of the rat erythropoietin receptor (EpoR) gene was identified in normal and erythroleukemia cells. A 105 bp insert was found at a region corresponding to the extracellular domain ofEpoR. The alternative transcript was translated to a soluble EpoR (EpoR-S) expressed in spleen, bone marrow, and cultured erythroleukemia cells in addition to the full-length EpoR (EpoR-F). One of the rat erythroleukemia sublines, K4DT, which partially lost erythroid phenotypes and manifested monocyte/macrophage characteristics also lacked EpoR-S expression. Thus, expression of EpoR-S may play an important role in differentiation of rat erythroid cells. (C) 1997 Elsevier Science Ireland Ltd.
  • H Fukunishi, K Murata, S Takeuchi, S Kitazawa
    ARCHIVES OF GYNECOLOGY AND OBSTETRICS 258 4 207 - 211 1996年07月 [有り][無し]
     研究論文(学術雑誌) 
    Ovarian fibromatosis is very rare, and the one with focal proliferations of sex cord type elements is extraordinarily rare. A 31-year-old patient developed the bilateral ovarian enlargements and complained of lower abdominal pain. Pathology indicated that these tumors were ovarian fibromatosis with minor sex cord elements. Our two-step operation involved the first right salpingo-oophorectomy for histological examination and the subsequent enucleation of the left ovarian tumor alone. The patient conceived 10 months after operation.
  • M Fujioka, K Shimada, S Kitazawa, S Maeda
    INTERNATIONAL JOURNAL OF CANCER 67 2 204 - 210 1996年07月 [有り][無し]
     研究論文(学術雑誌) 
    A cultured cell line (CaPA-4), derived from an undifferentiated carcinoma in a pleomorphic adenoma of the submandibular gland, was established through xenografted tumors in nude mice. Geneticin treatment eliminated surrounding mouse fibroblasts and yielded enriched tumor cells at an early stage of cell passage. In vitro, the line grew in a cobblestone pattern, revealing its epithelial origin. Chromosomal analysis by Giemsa-banding confirmed its human origin, while electron microscopic examination showed its squamous-cell characteristics. CaPA-4 cells stained positive for the c-myc and Ha-rot antibodies. Molecular analysis showed over-expression of both c-myc and Ha-ras mRNA, with point mutation of p53 at codon 248 and of Ha-ras at codon 61. Amplification and rearrangement of the Ha-ras gene were observed; however, no loss of heterozygosity (LOH) of the p53 gene was detected by Southern blotting. This sequence of cancer-related gene activation may represent the malignant transformation from benign pleomorphic adenoma. This report describes the establishment and molecular characterization of this novel cell line from carcinoma in pleomorphic adenoma exhibiting squamous-cell differentiation, This could represent a useful model for investigating the cause of malignant transformation from human salivary-gland mixed tumors. (C) 1996 Wiley-Liss, Inc.
  • H Liapis, A Flath, S Kitazawa
    DIAGNOSTIC MOLECULAR PATHOLOGY 5 2 127 - 135 1996年06月 [有り][無し]
     研究論文(学術雑誌) 
    Breast cancer metastasis to bone is a multistep process requiring attachment of tumor cells to the bone and bone marrow environment. The precise adhesion molecules involved in skeletal homing of breast cancer to bone are unknown but likely include integrins. We investigated the expression of vitronectin receptor (alpha(v) beta(3)) by breast cancer cells residing in bone because this heterodimer mediates osteoclast-bone recognition. We used immunohistochemistry and in situ hybridization in a systematic study of 22 bone biopsies containing breast cancer metastases and available samples of corresponding primary tumors and normal breast and compared alpha(v) beta(3), alpha(2) beta(1), and alpha(v) beta(5) integrin expression. The results showed that alpha(v) beta(3) was strongly expressed by normal breast epithelium and was decreased in same and strongly expressed in other primary invasive breast carcinomas. In contrast, this integrin heterodimer was abundant in all breast cancer cells metastatic to bone. In situ hybridization revealed high levels of steady-state mRNA corresponding to sites of protein expression; alpha(2) beta(1) was weakly expressed in both primary and metastatic tumors, and alpha(v) beta(5) was not detected. Our results showed an overexpression of alpha(v) beta(3) by bone-residing breast cancer cells and suggest either subclonal selection of alpha(v) beta(3)-expressing tumor cell populations or upregulation of alpha(v) beta(3) in the bone microenvironment.
  • M Sakaue, S Kitazawa, K Nishida, R Kitazawa, S Maeda
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 221 3 768 - 772 1996年04月 [有り][無し]
     研究論文(学術雑誌) 
    The bone morphogenic proteins (BMPs) constitute a novel subfamily of the transforming growth factor type beta (TGF-beta) supergene family and play a critical role in modulating mesenchymal differentiation and inducing the processes of cartilage and bone formation. In this study we isolated the 5'-flanking region of the human BMP-5 gene. Nucleotide sequencing, primer extension, DNase I foot printing and functional analysis by transient expression showed that the cloned 1.5 kb promoter region contains two transcription start sites, a canonical TATA box (-17 similar to -12) and a number of consensus recognition sequences including GATA-1 (-582 similar to -576) and engrailed (-549 similar to -541). (C) 1996 Academic Press, Inc.
  • T Ajiki, T Fujimori, H Onoyama, M Yamamoto, S Kitazawa, S Maeda, Y Saitoh
    GUT 38 3 426 - 429 1996年03月 [有り][無し]
     研究論文(学術雑誌) 
    Epithelial dysplasia of gall bladder is an important precancerous lesion of gall bladder carcinogenesis. To investigate the frequency of K-ras gene mutation in gall bladder carcinoma and dysplasia, K-ras codon 12 mutations were investigated by the polymerase chain reaction/restriction enzyme based method following direct sequencing. Mutation was detected in 59% (30 of 51) of gall bladder carcinomas, in 73% (8 of 11) of gall bladder dysplasia in gall stone cases, and in 0% of the normal gall bladder epithelium. There was, however, no correlation between K-ras mutation and clinicopathological factors of gall bladder carcinoma. K-ras gene mutation occurs even in gall bladder dysplasia at an incidence similar to that in carcinomas, suggesting that testing for K-ras gene mutation may prove useful as an adjunct to bile cytological or biopsy analysis.
  • Y Idei, S Kitazawa, T Fujimori, T Ajiki, K Asaka, S Takeuchi, M Mochizuki, T Chiba, S Maeda
    HUMAN PATHOLOGY 27 1 77 - 79 1996年01月 [有り][無し]
     研究論文(学術雑誌) 
    A rare case of ovarian small cell carcinoma is reported. Laboratory examination of a 46-year-old woman with a lower abdominal tumor showed marked hypercalcemia. Her condition deteriorated progressively, and she died one month after admission. A right ovarian tumor, 8 cm in diameter, metastases to multiple organs, and intraperitoneal bleeding were confirmed by autopsy. Microscopically, the small tumor cell had rounded nuclei with small distinct nucleoli and a scanty cytoplasm. Small cell carcinoma was diagnosed from these histological features and the clinical course associated with hypercalcemia. Immunohistochemical studies showed positive staining of neuron specific enolase (NSE) and keratin. Genetic analysis using DNA extracted from paraffin sections of metastatic lesions revealed mutation of K-ras codon 12. Loss of heterozygosity of the p53 and adenomatous polyposis coli (APC) genes was not informative. Previous reports have shown that ras gene mutations occur in 30% of epithelial ovarian tumors and significantly more frequently in mucinous than in other types of ovarian tumors. These results suggest that small cell carcinoma is of epithelial origin and may have a genetic alteration similar to that of mucinous tumors. HUM PATHOL 27:77-79. Copyright (C) 1996 by W.B. Saunders Company
  • Kohno N, Sakoda Y, Wakita K, Nishihara T, Kaneda K, Kawamura T, Kanwara Y, Ishikawa Y, Kitazawa S
    Biotherapy 10 9 1208 - 1213 1996年 [有り][無し]
  • Kanbara Y, Maekawa Y, Nakaya S, Ishikawa Y, Kitazawa S
    Acta Hepatologica Japonica 37 12 736 - 737 1996年 [有り][無し]
  • S KITAZAWA, S MAEDA
    CLINICAL ORTHOPAEDICS AND RELATED RESEARCH 312 45 - 50 1995年03月 [有り][無し]
     研究論文(学術雑誌) 
    Skeletal metastases result from a series of complex steps including activation of osteoclasts and interaction between adhesion molecules on cancer cells and bone matrices. Researchers of this study used pathologic specimens of breast cancer cells from primary and metastatic sites obtained at surgery or autopsy to demonstrate the expression of parathyroid hormone-related protein by immunohistochemistry and beta 3 integrin by in situ hybridization to clarify the role of tumor-derived osteoclast activating factors and adhesion molecules in the development of skeletal metastases. The results of this retrospective study showed a significant difference of parathyroid hormone-related protein and beta(3) integrin expression in cases with and without skeletal metastases, These expressions were enhanced or clonally selected or both in skeletal metastatic sites, Because activation of osteoclastic bone resorption by parathyroid hormone-related protein could facilitate tumor cells to attach to the eroded bone surface through cell adhesion molecules, these 2 factors could make it easier for tumor cells to grow in bone.
  • Kitazawa S, Ross F.P, McHugh K, Teitelbaum S.L
    Journal of Biological Chemistry 270 8 4115 - 4120 1995年02月 [有り][無し]
     研究論文(学術雑誌) 
    Osteoclastic bone resorption is dependent upon cell-matrix recognition. This process is mediated by the integrin alpha(v) beta(3), whose expression is enhanced, in avian osteoclast precursors, by bone-seeking steroids. The purpose of this study was to determine if bone-modulating cytokines impact on gp, expression by mouse marrow macrophages (BMMs), known to differentiate into osteoclasts. Of the cytokines tested. Interleukin-4 (IL-4) is most effective in increasing beta(3) mRNA levels by a mechanism involving transactivation of the beta(3), gene. Moreover, IL-4 augmented beta(3) mRNA is mirrored by plasma membrane appearance of alpha(v) beta(3). As IL-4 induces beta(3) and not alpha(v) mRNA, the beta(3) chain appears to regulate surface expression of the heterodimer. The functional significance of IL-4-induced alpha v beta 3, is underscored by the fact that, while attachment to fibronectin is unaltered, treatment of EMMs with the cytokine enhances alpha(v) beta(3)- mediated binding to vitronectin 5-fold, Expression of this heterodimer by BMMs driven along a non-osteoclastic lineage suggests alpha(v) beta(3), may play a role in the inflammatory response of macrophages.
  • Gotoh A, Mizuno Y, Okada H, Arakawa S, Kitazawa S, Maeda S, Kamidono S
    In Vivo 9 3 263 - 267 1995年 [有り][無し]
  • Ishido S, Yokoyama M, Kitazawa S, Maeda S
    The American journal of cardiovascular pathology 5 1 49 - 54 1995年 [有り][無し]
  • H FUKUNISHI, N YUKIMURA, S TAKEUCHI, S KITAZAWA
    INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS 46 3 321 - 324 1994年09月 [有り][無し]
     
    Objectives: To conduct a pathological characterization of rare uterine myxoid leiomyosarcoma (MLS) and establish an effective chemotherapy for metastasis after hysterectomy. Methods: Histological and immunohistochemical methods were used to characterize the type of uterine MLS in a 39-year-old female. For multiple lung metastases found 3 months after operation, CYVADIC (400 mg cyclophosphamide, 1 mg vincristine, 50 mg epirubicin and 400 mg dacarbazine per body for one course) and oral etoposide (50 mg/body per day for 2 weeks) were applied. Results: The rapidly enlarging uterine tumors exhibited gelatinous cut surfaces, a high count of 30 mitotic cells per 10 hpf and mucinous stroma, indicating a rare high-mitotic type of uterine MLS. The two-course CYVADIC-etoposide therapy was effective for disseminated pulmonary metastases. Conclusion: The present MLS was a rare high-mitotic type. CYVADIC-etoposide was an optional effective chemotherapy for lung metastasis in this case.
  • T TERAMOTO, K SATONAKA, S KITAZAWA, T FUJIMORI, K HAYASHI, S MAEDA
    CANCER RESEARCH 54 1 231 - 235 1994年01月 [有り][無し]
     研究論文(学術雑誌) 
    Hepatocellular carcinoma (HCC) accumulates a mutation of the p53 gene with a common substitution of nucleotide in a particular site. It is hypothesized that infection of hepatitis B virus (HBV) or exposure to aflatoxins could induce it. In Japan, the concentration of aflatoxins in the environment is low; however, infection of HBV and/or hepatitis C virus (HCV) is frequently seen in patients with HCC. The purpose of our studies was to determine whether these hepatoviral factors influence p53 alterations. In our results, p53 abnormalities, which were composed of loss of heterozygosity (LOH) and/or point mutation, were shown in 39% of patients. We postulated that they occurred at late stages in tumor growth based on the following two results. LOH analysis on p53 showed that most of the tumor nodule consisted of two phenotypes, LOH and non-LOH cancer cells. The p53 abnormalities correlated with the grade of cancer cell atypia which advanced with tumor growth. HBV and HCV infections were identified by polymerase chain reaction using DNA extracted from cancerous and noncancerous regions of the liver. By these methods, the patients who had been infected with either HBV or HCV showed an incidence of p53 abnormalities (45%) higher than those infected by neither (13%). However, the detection rate of these viruses was lower in the HCC region (33%) than that in the noncancerous region (56%) in cases with mutated p53. The low rate of HCV detection (22%) in the HCC region with altered p53 was attributable to these different viral detection rates. There was a difference in pattern of p53 mutational changes in patients depending upon whether they were infected by HBV or by HCV. Two of three HBV-infected patients had a transversional change of nucleotide at the G:C site to T.A. However, in cases with HCV, four of eight patients had a transitional change of nucleotide of p53. These results showed that HBV and HCV infections affect carcinogenic pathways causing p53 abnormalities independently.
  • Gotoh A, Mizuno Y, Matsuwari S, Kitazawa S, Maeda S, Arakawa S, Kamidono S
    Gan To Kagaku Ryoho 21 6 899 - 902 1994年 [有り][無し]
  • N KOHNO, S KITAZAWA, M FUKASE, Y SAKODA, Y KANBARA, Y FURUYA, O OHASHI, Y ISHIKAWA, Y SAITOH
    SURGERY TODAY-THE JAPANESE JOURNAL OF SURGERY 24 3 215 - 220 1994年 [有り][無し]
     研究論文(学術雑誌) 
    The relationship between the expression of parathyroid hormone-related protein (PTHrP) by breast cancer and skeletal metastases, was investigated using a monoclonal antibody against human PTHrP (4B3). The immunohistochemical localization of PTHrP was studied in sections of formalin-fixed, paraffin-embeded tissues from 28 breast cancers obtained surgically between 1980 and 1985. Of the 28 patients, 12 developed skeletal metastases, 8 developed lung metastases, and the other 8 were alive and disease-free at the time of this study. Sixteen of the 28 (57%) tumors showed positive immunoreactivity to 4B3, the PTHrP positive ratio being 83% in the patients who developed skeletal metastases, 38% in those who developed lung metastases, and 38% in those without recurrence, respectively. Thus, a significantly higher proportion of the patients who developed skeletal metastases were positive for PTHrP than the other two groups (P < 0.05). Furthermore, the level of positive staining was strongly related to positivity for estrogen and progesterone receptors (P < 0.01). These results are consistent with the hypothesis that PTHrP might be necessary for metastases to erode bone and grow in skeletal sites, and its expression could be related to certain hormones.
  • Kohno N, Kitazawa S, Sakoda Y, Kanbara Y, Furuya Y, Ohashi O, Kitazawa R
    Breast Cancer 1 1 43 - 49 1994年 [有り][無し]
  • Fukunishi H, Yukimura N, Murata K, Gotoh A, Kitazawa R, Kitazawa S
    Journal of Bone and Mineral Metabolism 12 1 Supplement 1994年 [有り][無し]
  • Gotoh A, Mizuno Y, Matsuwari S, Kitazawa S, Maeda S, Arakawa S, Kamidono S
    Japanese Journal of Cancer and Chemotherapy 21 6 899 - 902 1994年 [有り][無し]
  • Kitazawa R, Kitazawa S, Fukunishi H, Kohno N, Gotoh A, Yamamura-Idei Y, Fukase M, Chihara K, Fujita T, Maeda S
    Journal of Bone and Mineral Metabolism 12 1 Supplement 1994年 [有り][無し]
  • H LIAPIS, EC CROUCH, LE GROSSO, S KITAZAWA, MR WICK
    AMERICAN JOURNAL OF PATHOLOGY 143 4 1169 - 1178 1993年10月 [有り][無し]
     研究論文(学術雑誌) 
    Parathyroidlike peptide (PLP), or parathyroid hormone-related protein, is a protein of uncertain biological function that is structurally homologous to parathyroid hormone. Immunohistochemical studies have identified amino-terminal epitopes of PLP in breast carcinomas, but not in normal breast. In the present studies, immunohistochemistry and in situ hybridization were performed to evaluate further expression of PLP in normal, proliferative, and neoplastic breast tissues. Using a polyclonal antibody that recognizes epitopes within the middle and carboxyl-terminal domains of PLP, immunoreactive protein was detected within the cytoplasm of lobular and ductal epithelial cells in all normal and fibrocystic breast tissues from 74 patients. The intensity of cytoplasmic staining was increased in association with lactation, adenosis, and simple or atypical ductal hyperplasia and decreased in atrophic lobules. Cytoplasmic reactivity was also observed in 69% (56 of 81) of breast adenocarcinomas. Expression of immunoreactive PLP was inversely correlated with tumor stage and extent of nodal involvement at the time of diagnosis. However, there was no significant correlation with tumor grade, patient age, or hormone receptor status. In situ hybridization studies confirmed the epithelial expression of PLP messenger RNA in PLP-positive normal and neoplastic breast tissue. Interestingly, tumor-associated calcifications were identified in 43% of PLP-positive carcinomas, but in only 12% of PLP-negative carcinomas (P < 0.007). Our results suggest that PLP plays some role in the normal differentiated function of mammary epithelial cells and are consistent with the hypothesis that expression of this protein influences local calcium metabolism.
  • Y YAMAMURAIDEI, S KITAZAWA, R KITAZAWA, T FUJIMORI, T CHIBA, S MAEDA
    CANCER 72 6 1849 - 1852 1993年09月 [有り][無し]
     研究論文(学術雑誌) 
    Background. Parathyroid hormone-related protein (PTHrP) has been regarded as one of the substances causing humoral hypercalcemia of malignancy. Methods. The immunohistochemical localization of PTHrP was investigated in 33 cases of gastric cancer (4 with heterotopic ossification and 29 without heterotopic ossification) to clarify the role of PTHrP in heterotopic ossification by using the anti-PTHrP monoclonal antibody, 4B3. Results. The four cases with heterotopic ossification showed positive staining at primary or metastatic sites, and in one case fibroblasts in the stroma surrounding the heterotopic ossifying foci also showed positive. On the other hand, of the 29 cases without heterotopic ossification, only 5 showed positive staining. Conclusions. The presence of PTHrP in ossifying gastric carcinomas at a relatively high rate indicates that PTHrP also might be related to heterotopic ossification associated with malignancies. It is speculated that PTHrP would contribute to heterotopic ossification by facilitating the process of mineralization.
  • S KITAZAWA, R KITAZAWA, A GOTOH, T FUJIMORI, S MAEDA
    BIOTECHNIC & HISTOCHEMISTRY 68 3 137 - 141 1993年05月 [有り][無し]
     研究論文(学術雑誌) 
    We developed a modified in situ DNA-RNA hybridization technique and demonstrated c-myc proto-oncogene transcripts in nodular sclerosis type Hodgkin's disease (HD-NS). A hybridization probe was prepared by metabolic labelling of bromodeoxyuridine (BrdU). The hybridized probe was detected with anti-BrdU monoclonal antibody after incubation with ribonuclease H (RNase H), which specifically degrades RNA from DNA-RNA hybrids. In HD-NS, c-myc proto-oncogene transcripts were demonstrated in the cytoplasm of lacuna cells and a few surrounding lymphoid cells. This modified hybridization method was sensitive and applicable to the study of oncogene expression at a single cell level.
  • CH YAO, S KITAZAWA, T FUJIMORI, S MAEDA
    BIOTECHNIC & HISTOCHEMISTRY 68 3 169 - 174 1993年05月 [有り][無し]
     研究論文(学術雑誌) 
    A bromodeoxyuridine (BrdU) labeled DNA probe was used for in situ hybridization at the electron microscopic (EM) level. A BrdU labeled DNA probe was hybridized in situ to cryostat sections of paraformaldehyde fixed OCT compound embedded cultured HL-60 cells. After hybridization, some sections were incubated with FiTC-conjugated anti-BrdU monoclonal antibody for fluorescence microscopy (FM), and others were embedded in Quetol for electron microscopy (EM). The ultrathin sections of Quetol-embedded specimens were incubated with the anti-BrdU monoclonal antibody and the immunoglobulin: gold colloid. In both FM and EM studies, the signals were concentrated in the rough endoplasmic reticulum. Moreover, some label was arranged from the nucleus to the cytoplasm at the EM level. Relatively simple methods using the BrdU labeled DNA probe for the detection of the defined nucleic acid sequence with reasonable tissue preservation and high resolution are described here. This method may be useful for developmental and disease related studies of specific mRNA in cells and tissues.
  • A GOTOH, S KITAZAWA, Y MIZUNO, A TAKENAKA, S ARAKAWA, O MATSUMOTO, R KITAZAWA, T FUJIMORI, S MAEDA, S KAMIDONO
    CANCER 71 9 2803 - 2806 1993年05月 [有り][無し]
     研究論文(学術雑誌) 
    Background. Parathyroid hormone-related protein (PTHrP) is the predominant cause of humoral hypercalcemia of malignancy (HHM). Methods. Using a PTHrP-specific monoclonal antibody (MoAb), 4B3, the authors investigated the immunohistochemical localization of PTHrP in formalin-fixed and paraffin-embedded sections of normal human kidney tissues and tissues from 42 human renal cell carcinomas obtained at operation or autopsy. Results. In normal renal tissues, the distal tubules and collecting ducts showed positive immunostaining. PTHrP was detected in 40 of 42 renal cell carcinoma tissues (95%). Histopathologically, the granular cell subtypes of renal cell carcinomas tended to be more strongly positive than the clear cell subtypes. There was no significant correlation between the level of immunostaining and each patient's serum calcium level. Conclusion. PTHrP was commonly observed in renal cell carcinomas, and no significant correlation was seen between the intensity of PTHrP staining and the serum calcium level.
  • H SHIMOGAKI, S KITAZAWA, S MAEDA, S KAMIDONO
    CANCER JOURNAL 6 2 81 - 86 1993年03月 [有り][無し]
     研究論文(学術雑誌) 
    Some investigators have reported that certain proto-oncogene products play an important role in normal cellular growth and/or differentiation and in the response to proliferative signals. We have investigated 24 testicular germ cell tumors for the expression of hst-1, int-2, parathyroid hormone-related protein (PTHrP), Ki-ras and N-myc at the RNA levels using Northern blot analysis. We also investigated PTHrP expression immunohistochemically using a monoclonal anti-PTHrP antibody. There was a significant difference in hst-1 expression between seminomas and nonseminomas, since expression was detected in 6 out of 8 (75%) nonseminomas and only 1 out of 15 (7%) seminomas. No association was found between tumor stage and Ki-ras or N-myc expression, and no int-2 mRNA was detected in the germ cell tumors. PTHrP is one of the main factors of humoral hypercalcemia of malignancy. It was also recently found in normal human tissue and has been suggested to play an important role in the differentiation of keratinocytes, endocrine tissue, and extraembryonic elements. The immunohistochemical localization of PTHrP correlated well with in situ hybridization and Northern blot findings. PTHrP was detected in all seminomas and in choriocarcinoma tumor elements of the mixed type, irrespective of the serum calcium level. In seminomas, PTHrP was expressed as the common form at the transcriptional level (1.4 and 2.2 kb by Northern blot analysis) and was characteristically located in the nucleus by immunostaining. The presence of PTHrP in choriocarcinoma tumor elements might reflect their functional and phenotypic similarity to placental tissue. PTHrP expression was not detected in embryonal carcinomas or teratomas. Thus, the phenotypic differentiation of embryonic and extraembryonic elements seems to be unrelated to the expression and localization of PTHrP.
  • T YAMAGUCHI, H KIDO, R KITAZAWA, S KITAZAWA, M FUKASE, N KATUNUMA
    JOURNAL OF BIOCHEMISTRY 113 3 299 - 303 1993年03月 [有り][無し]
     研究論文(学術雑誌) 
    The structure and location of a membrane-bound metallo-endopeptidase, previously purified from rat kidney [Yamaguchi et al. (1991) Eur. J. Biochem. 200, 563-571], were examined by immunochemical and immunohistochemical methods with a rabbit polyclonal antibody against the purified enzyme. On treatment with endoglycosidase F, the subunit of the purified enzyme (molecular mass = 88 kDa) was converted to a smaller form (78.5 kDa), indicating that the enzyme contained at least 11% N-linked carbohydrate. Treatment of kidney membranes with papain resulted in release of the enzyme, as shown by Western blotting analysis of the solubilized fraction. Immunoassays of rat tissues showed that only the kidney, and small and large intestine expressed significant amounts of the antigen. Moreover, immunohistochemical studies showed that the antigen was confined to the luminal surfaces of the proximal renal tubules and the intestinal villi. Thus, like another kidney membrane metallo-endopeptidase, meprin [Kounnas et al. (1991) J. Biol. Chem. 266, 17350-17357], the purified enzyme is shown to be a glycoprotein that is probably anchored in the plasma membrane, and located in the luminal surface of microvillar membranes of the kidney and intestine. These results indicate that our enzyme and meprin have clear structural and topological similarities.
  • Kanbara Y, Kono N, Nakaya M, Ishikawa Y, Fujiwara O, Kitazawa R, Kitazawa S
    Nippon Geka Gakkai Zasshi 94 4 394 - 9 1993年 [有り][無し]
  • Mizuno Y, Gotoh A, Kamidono S, Kitazawa S
    Nippon Hinyokika Gakkai Zasshi 84 7 1211 - 8 1993年 [有り][無し]
  • Ohta T, Takeuchi S, Ohara N, Deguchi M, Mochizuki M, Kitazawa S, Maeda S
    Nippon Sanka Fujinka Gakkai Zasshi 45 11 1337 - 40 1993年 [有り][無し]
  • S KITAZAWA, R KITAZAWA, CH YAO, S MAEDA
    ACTA HISTOCHEMICA ET CYTOCHEMICA 26 4 295 - 301 1993年 [有り][無し]
     研究論文(学術雑誌) 
    In the current study, we developed an improved method for ISH at the electron microscopic level, in which we employed pre-embedding hybridization using a BrdU labeled probe followed by post-embedding immunoglobuline gold colloid staining (IGS). Because metabolic labeling of BrdU provides an almost evenly labeled DNA probe with high labeling index, pre-embeddingly hybridized BrdU-labeled probe preserves its detectable antigenicity even after the preparation of ultrathin sections. We demonstrated precise cell identification, early stage of gene expression and alternative splicing patterns using this technique.
  • Kanbara Y, Kono N, Nakaya M, Ishikawa Y, Fujiwara O, Kitazawa R, Kitazawa S
    Nippon Geka Gakkai zasshi 94 4 394 - 399 1993年 [有り][無し]
  • Mizuno Y, Gotoh A, Kamidono S, Kitazawa S
    Japanese Journal of Urology 84 7 1211 - 1218 1993年 [有り][無し]
  • Ohta T, Takeuchi S, Ohara N, Deguchi M, Mochizuki M, Kitazawa S, Maeda S
    Acta Obstetrica et Gynaecologica Japonica 45 11 1337 - 1340 1993年 [有り][無し]
  • R KITAZAWA, S KITAZAWA, M FUKASE, T FUJITA, A KOBAYASHI, K CHIHARA, S MAEDA
    HISTOCHEMISTRY 98 4 211 - 215 1992年11月 [有り][無し]
     研究論文(学術雑誌) 
    The expression and localization of parathyroid hormone-related protein (PTHrP), a major factor responsible for humoral hypercalcemia of malignancy (HHM), was investigated in 14 cases of surgically resected normal parathyroid glands. For light microscopic immunohistochemistry, formalin-fixed and paraffin-embedded specimens were stained with avidin-biotin-peroxidase complex (ABC) using the anti-PTHrP monoclonal antibody (MoAb), 4B3. Four percent paraformaldehyde (PFA)-fixed and OCT compound-embedded specimens were used for pre-embedded immunoelectron microscopy. For in situ hybridization, 4% PFA-fixed, frozen sections were studied using a bromodeoxyuridine (BrdU)-labeled PTHrP cDNA probe. Immunohistochemically, 12 of the 14 cases were positive for PTHrP, which was observed mainly in the oxyphil and transitional oxyphil cells. The chief and clear cells, on the other hand, were faintly positive. Electron microscopically, secretory granules positive for PTHrP were observed in cells containing abundant mitochondria. Consistent with the PTHrP immunoreactivity, transcripts of PTHrP were observed also in the oxyphilic cells by in situ hybridization. Thus the production and secretion of PTHrP was shown by the oxyphil cell lineage in the normal parathyroid glands.
  • S KITAZAWA, N SHIRAISHI, S MAEDA
    ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA 71 6 482 - 484 1992年08月 [有り][無し]
     研究論文(学術雑誌) 
    We report a rare autopsy case of leiomyomatosis peritonealis disseminata in a woman, who had been operated upon for ovarian granulosa cell tumor two years prior to her death. The deposits showed both myofibroblastic and adipocytic differentiation.
  • D HIRAYAMA, T FUJIMORI, K SATONAKA, T NAKAMURA, S KITAZAWA, M HORIO, S MAEDA, K NAGASAKO
    HUMAN PATHOLOGY 23 6 681 - 685 1992年06月 [有り][無し]
     研究論文(学術雑誌)
  • S KITAZAWA, T FUJIMORI, R KITAZAWA, S MAEDA
    CANCER JOURNAL 5 3 132 - 136 1992年05月 [有り][無し]
  • T FUJIMORI, D HIRAYAMA, A GOTOH, T TABATA, M YUKAWA, Y YAMAMURA, K SATONAKA, T NAKAMURA, T TERAMOTO, S KITAZAWA, S MAEDA, J MEDERIOS, K NAGASAKO
    GASTROENTEROLOGIA JAPONICA 27 2 187 - 190 1992年04月 [有り][無し]
     研究論文(学術雑誌) 
    Leiomyoblastoma has been regarded as a neoplasm of smooth muscle origin. With recent progress in immunohistostaining techniques, many clinicopathological discrepancies have been pointed out about the origin of leiomyoblastoma. It has been claimed that gastrointestinal non-epithelial tumors should be regarded as stromal tumors in order to study their origin. In the present study, we performed various forms of immunohistostaining in seven cases of leiomyoblastoma to determine their origin. One case expressed desmine and muscle specific actin and was considered to be derived from smooth muscle. Four neoplasms expressed S-100 protein (two cases were also NSE positive) and were thought to be derived from the nerve. Two cases were of unknown derivation. These results suggest that the cells of leiomyoblastoma may arise from a primitive to totipotential cell of neural lineages that may anomalously express smooth muscle filaments.
  • Kitazawa S, Kitazawa R, Fukase M, Fujimori T, Maeda S
    International Journal of Cancer 50 5 731 - 735 1992年03月 [有り][無し]
     研究論文(学術雑誌) 
    We investigated the immunohistochemical localization of parathyroid hormone-related protein (PTHrP), a major factor responsible for the humoral hypercalcemia of malignancy, in uterine cervical lesions. Formalin-fixed paraffin-embedded specimens from 16 cases of normal and reactive conditions, 45 cases of cervical intra-epithelial neoplasm (CIN) and 63 cases of invasive cancer were studied immunohistochemically by the avidine-biotin-peroxidase method, using an anti-PTHrP monoclonal antibody (MAb), 4B3. In normal and reactive conditions, PTHrP was positive in parabasal cells, squamous metaplasia, and hyperplastic reserve cells. In neoplastic conditions, 96% (43/45) of invasive squamous-cell carcinomas were positive for PTHrP, regardless of the patients' serum calcium levels. Two cases with hypercalcemia were strongly positive for PTHrP and showed prominent stromal interaction of the scirrhous type. In CIN, including koilocytic atypia, 76% (32/42) of cases were positive for PTHrP. In contrast, 91% (10/11) of adenocarcinomas were negative for PTHrP. In conclusion, we found, first, that in non-neoplastic conditions, the presence of PTHrP was correlated with the transformation of progenitor cells into squamous epithelia and with the maturation of keratinocytes and, second, that in squamous-cell carcinoma, the degree of keratinization and stromal interaction was higher in direct proportion to the apparent incidence of detectable PTHrP.
  • T FUJIMORI, T NAKAMURA, D HIRAYAMA, K SATONAKA, T AJIKI, S KITAZAWA, S MAEDA, K NAGASAKO, H YAMAGUCHI, S YOSHIDA
    ENDOSCOPY 24 3 187 - 189 1992年03月 [有り][無し]
     研究論文(学術雑誌) 
    We present a modification of strip biopsy (SB), one of the endoscopic treatment modalities for early gastric cancer. Using a side-viewing endoscope and a special electrocautery snare, we treated 6 patients with early carcinoma of the intestinal type with this modified strip biopsy (MSB). All tumors could be completely resected and 5 patients were not operated on: All 5 remained tumor-free at follow-up of at least one year. These results compared favorably with a historical control group of 17 patients with early gastric cancer treated with conventional strip biopsy. We therefore recommend applying our new method of MSB especially in the intestinal type of early gastric carcinoma; these preliminary data however, need confirmation in larger trials.
  • Yamashita M, Goto A, Kamidono S, Sengoku A, Kitano Y, Oda Y, Umezu K, Kitazawa S
    Hinyokika Kiyo 38 7 825 - 8 1992年 [有り][無し]
  • Yamashita M, Goto A, Kamidono S, Sengoku A, Kitano Y, Oda Y, Umezu K, Kitazawa S
    Acta Urologica Japonica 38 7 825 - 828 1992年 [有り][無し]
  • HIRAYAMA D, FUJIMORI T, SATONAKA K, YUKAWA M, TERAMOTO T, KITAZAWA S, MAEDA S, NAGASAKO K, ARAO M
    Digestive Endoscopy 4 1 31 - 36 1992年 [有り][無し]
  • Y BESSHO, O KATAOKA, T SHO, S KITAZAWA, S OKADA
    SPINE 16 8 988 - 990 1991年08月 [有り][無し]
  • S KITAZAWA, M FUKASE, R KITAZAWA, A TAKENAKA, A GOTOH, T FUJITA, S MAEDA
    CANCER 67 4 984 - 989 1991年02月 [有り][無し]
     研究論文(学術雑誌) 
    With a newly developed monoclonal anti-PTHrP antibody, 4B3, the immunohistochemical localization of the parathyroid hormone-related protein (PTHrP) was studied on the formalin-fixed and paraffin-embedded sections of normal human tissues and various subtypes of lung cancer. Among normal epithelial tissues, keratinocytes in squamous epithelia, transitional and bronchial epithelia with squamous metaplasia, meningoepithelial cells, and mammary ductal cells with lactating changes showed positive immunoreactivity. Also, among endocrine tissues, cells in the parathyroid gland, pancreatic islets, adrenal cortex, pituitary gland, and testis were sporadically positive for PTHrP. These distribution patterns suggested that in a physiologic condition, PTHrP was closely related to keratinization and local secretion and/or the metabolism of calcium in specifically differentiated tissues. In lung cancer, however, PTHrP was detected in all cases of well-differentiated and moderately differentiated squamous cell carcinoma and in most cases of small cell carcinoma, irrespective of the patients' serum calcium level. However, PTHrP was not detected in two of five cases of poorly differentiated squamous cell carcinoma and in all cases of adenocarcinoma. Consequently, it was found that PTHrP was commonly produced by squamous cell carcinomas of the differentiated type, and that humoral hypercalcemia of malignancy could be induced when the PTHrP transgressed the homeostatic mechanisms.
  • Gotoh A, Kitazawa S, Fukase M, Ogawa T, Arakawa S, Fujimori T, Maeda S, Kamidono S
    Nippon Hinyokika Gakkai Zasshi 82 4 588 - 92 1991年 [有り][無し]
  • Gotoh A, Ogawa T, Arakawa S, Kamidono S, Fujimori T, Maeda S, Kitazawa S, Fukase M
    Japanese Journal of Urology 82 4 588 - 592 1991年 [有り][無し]
  • K KARIO, S MAEDA, Y MIZUNO, Y MAKINO, H TANKAWA, S KITAZAWA
    JOURNAL OF SURGICAL ONCOLOGY 45 1 46 - 51 1990年09月 [有り][無し]
     研究論文(学術雑誌)
  • HISTO-INSITU HYBRIDIZATION USING INVIVO METABOLICALLY-LABELED BROMODEOXYURIDINE DNA PROBES AND APPLICATION TRIAL FOR PATHOLOGICAL DIAGNOSIS
    S MAEDA, S KITAZAWA, M HORIO, K SATONAKA, T FUJIMORI
    ACTA HISTOCHEMICA ET CYTOCHEMICA 23 3 401 - 409 1990年 [有り][無し]
     研究論文(学術雑誌)
  • Gotoh A, Fujimori T, Takenaka A, Hirayama D, Satonaka K, Horio M, Kitazawa S, Maeda S, Kamidono S
    Gan No Rinsho 36 7 857 - 61 1990年 [有り][無し]
  • A TAKENAKA, S KITAZAWA, S MAEDA, S KAMIDONO
    HISTOCHEMISTRY 94 1 27 - 30 1990年 [有り][無し]
     研究論文(学術雑誌)
  • S KITAZAWA, S MAEDA, T SUGIYAMA
    MEDICAL ONCOLOGY AND TUMOR PHARMACOTHERAPY 7 1 35 - 41 1990年 [有り][無し]
     研究論文(学術雑誌)
  • Takenaka A, Gotoh A, Hara I, Gohji K, Ogawa T, Arakawa S, Matsumoto O, Kamidono S, Hamami G, Itani A, Harada K, Tadera S, Kitazawa S, Maeda S
    Japanese Journal of Cancer and Chemotherapy 17 9 1909 - 1915 1990年 [有り][無し]
  • Takenaka A, Gohji K, Arakawa S, Matumoto O, Kamidono S, Mizutori M, Kitazawa S, Maeda S, Sugiyama T
    Hinyokika Kiyo 35 8 1439 - 44 1989年 [有り][無し]
  • Takenaka A, Kitazawa S, Koyama T, Fujimori T, Gotoh A, Gohji K, Maeda S, Kamidono S
    Nippon Hinyokika Gakkai Zasshi 80 12 1769 - 75 1989年 [有り][無し]
  • Kitazawa S, Maeda S, Horio M, Sugiyama T
    Gan No Rinsho 35 4 486 - 92 1989年 [有り][無し]
  • Takenaka A, Gohji K, Arakawa S, Matumoto O, Kamidono S, Mizutori M, Kitazawa S, Maeda S, Sugiyama T
    Acta Urologica Japonica 35 8 1439 - 1444 1989年 [有り][無し]
  • Takenaka A, Gotoh A, Gohji K, Kamidono S, Kitazawa S, Takenaka A, Gotoh A, Koyama T, Maeda S, Fujimori T
    The Japanese Journal of Urology 80 12 1769 - 1775 1989年 [有り][無し]
  • S KITAZAWA, A TAKENAKA, N ABE, S MAEDA, M HORIO, T SUGIYAMA
    HISTOCHEMISTRY 92 3 195 - 199 1989年 [有り][無し]
     研究論文(学術雑誌)
  • Maeda S, Horio M, Kitazawa S, Sugiyama T
    Gan No Rinsho 34 10 1264 - 72 1988年 [有り][無し]
  • Fukumura Y, Takahashi R, Maeda S, Kitazawa S, Sugiyama T
    Gan No Rinsho 33 1 76 - 81 1987年 [有り][無し]

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]
  • 術後に稀な骨盤内嚢胞性疾患と診断された2症例
    甲谷 秀子, 松原 圭一, 金子 久恵, 田坂 美恵, 北澤 荘平 日本産科婦人科内視鏡学会雑誌 33 (Suppl.I) 1350 -1350 2017年08月 [無し][無し]
  • 側脳室内に発生したPilocytic astrocytomaの1例
    西川 真弘, 瀬野 利太, 麻生 健伍, 末廣 諭, 山下 大介, 高野 昌平, 松井 誠司, 水野 洋輔, 北澤 荘平, 國枝 武治 Brain Tumor Pathology 34 (Suppl.) 134 -134 2017年05月 [無し][無し]
  • 側脳室内に発生したPilocytic astrocytomaの1例
    西川 真弘, 瀬野 利太, 麻生 健伍, 末廣 諭, 山下 大介, 高野 昌平, 松井 誠司, 水野 洋輔, 北澤 荘平, 國枝 武治 Brain Tumor Pathology 34 (Suppl.) 134 -134 2017年05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]
  • 結晶蓄積組織球症を伴ったMALTリンパ腫
    上田 康雄, 水野 洋輔, 北澤 理子, 北澤 荘平 日本病理学会会誌 106 (1) 374 -374 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]
  • 愛媛大学病理解剖施設改修と運用
    北澤 理子, 北澤 荘平 日本病理学会会誌 106 (1) 416 -416 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]
  • 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 竜馬, 北澤 理子, 北澤 荘平 日本病理学会会誌 106 (1) 512 -512 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]
  • 反応性尿路上皮細胞と尿路上皮癌細胞の鑑別におけるvimentinの有用性について
    佐伯 勇輔, 大崎 博之, 此上 武典, 藤田 泰吏, 北澤 荘平 医学検査 66 (1) 1 -7 2017年01月 [無し][無し]
     
    尿細胞診は、尿路系悪性腫瘍のスクリーニングや経過観察に欠かすことのできない検査であるが、他領域の細胞診に比べ誤陽性の比率が高いという問題がある。特に、尿路結石患者の尿中に出現する反応性尿路上皮細胞は、形態学的に尿路上皮癌細胞に類似するため、誤陽性の原因となっている。そこで今回は、反応性尿路上皮細胞と尿路上皮癌細胞を客観的に鑑別することを目的として、vimentinを用いた免疫細胞化学的検討を行った。反応性尿路上皮細胞群18症例、尿路上皮癌細胞群17症例、正常尿路上皮細胞群21症例を対象とした。上記症例にvimentinを用いた免疫細胞化学を行い、1)各群における症例別のvimentin陽性率、2)各群における全細胞集団別のvimentin陽性率、3)反応性尿路上皮細胞群における結石の存在部位とvimentin陽性率の3項目について比較検討を行った。症例別と全細胞集団別のvimentin陽性率においては、反応性尿路上皮細胞群が尿路上皮癌細胞群・正常尿路上皮細胞群よりも有意に高い結果を示した。結石の存在部位とvimentin陽性率では、腎盂の方が尿管よりも有意に高いvimentin陽性率を呈した。今回の検討で、尿路結石症例に出現する反応性尿路上皮細胞のvimentin陽性率は、尿路上皮癌細胞よりも有意に高いことが明らかになった。以上よりvimentinを用いた免疫細胞化学は両者の客観的な鑑別に有用である。(著者抄録)
  • 佐伯 勇輔, 大崎 博之, 此上 武典, 藤田 泰吏, 北澤 荘平 医学検査 66 (1) 1 -7 2017年01月 [無し][無し]
     
    尿細胞診は、尿路系悪性腫瘍のスクリーニングや経過観察に欠かすことのできない検査であるが、他領域の細胞診に比べ誤陽性の比率が高いという問題がある。特に、尿路結石患者の尿中に出現する反応性尿路上皮細胞は、形態学的に尿路上皮癌細胞に類似するため、誤陽性の原因となっている。そこで今回は、反応性尿路上皮細胞と尿路上皮癌細胞を客観的に鑑別することを目的として、vimentinを用いた免疫細胞化学的検討を行った。反応性尿路上皮細胞群18症例、尿路上皮癌細胞群17症例、正常尿路上皮細胞群21症例を対象とした。上記症例にvimentinを用いた免疫細胞化学を行い、1)各群における症例別のvimentin陽性率、2)各群における全細胞集団別のvimentin陽性率、3)反応性尿路上皮細胞群における結石の存在部位とvimentin陽性率の3項目について比較検討を行った。症例別と全細胞集団別のvimentin陽性率においては、反応性尿路上皮細胞群が尿路上皮癌細胞群・正常尿路上皮細胞群よりも有意に高い結果を示した。結石の存在部位とvimentin陽性率では、腎盂の方が尿管よりも有意に高いvimentin陽性率を呈した。今回の検討で、尿路結石症例に出現する反応性尿路上皮細胞のvimentin陽性率は、尿路上皮癌細胞よりも有意に高いことが明らかになった。以上よりvimentinを用いた免疫細胞化学は両者の客観的な鑑別に有用である。(著者抄録)
  • 巨大副腎褐色細胞腫の1例
    新井 欧介, 野田 輝乙, 福本 哲也, 三浦 徳宣, 柳原 豊, 宮内 勇貴, 菊川 忠彦, 雑賀 隆史, 北澤 荘平 西日本泌尿器科 78 (12) 634 -634 2016年12月 [無し][無し]
  • 愛媛大学病理解剖施設改修と運用
    北澤 理子, 北澤 荘平 日本病理学会会誌 105 (2) 93 -93 2016年09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]
  • 近藤 武史, 北澤 理子, 北澤 荘平 内科 117 (6) 1396 -1396 2016年06月 [無し][無し]
  • 近藤 武史, 北澤 荘平 内科 117 (5) 1259 -1259 2016年05月 [無し][無し]
  • 透明中隔から発生したdysemryoplastic neuroepithelial tumorの1例
    高野 昌平, 瀬野 利太, 岩田 真治, 水野 洋輔, 北澤 荘平, 大上 史朗, 大西 丘倫 Brain Tumor Pathology 33 (Suppl.) 127 -127 2016年05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]
  • 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 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]
  • 高血糖による酸化的ストレス付加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したDCMの一例
    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]
  • Padlock probeを用いたH-RCA法による組織切片上でのp16遺伝子メチル化シグナル検出
    二宮 鴻介, 北澤 荘平, 原口 竜摩, 北澤 理子 日本病理学会会誌 105 (1) 601 -601 2016年04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 105 (1) 604 -604 2016年04月 [無し][無し]
  • 細胞の分裂・分化、細胞系譜と組織形成 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
    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]
  • 骨巨細胞腫の原因遺伝子と抗RANKL抗体を用いた治療法の開発
    北澤 荘平, 北澤 理子 病理と臨床 33 (9) 1021 -1023 2015年09月 [無し][無し]
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    北澤 理子, 水野 洋輔, 北澤 荘平 日本病理学会会誌 104 (2) 59 -59 2015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, 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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    森山 直紀, 安念 優, 松本 紘典, 馬越 健介, 菊池 聡, 竹葉 淳, 相引 眞幸, 北澤 理子, 北澤 荘平 日本臨床救急医学会雑誌 18 (2) 437 -437 2015年04月 [無し][無し]
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    北澤 荘平 愛媛医学 34 (1) 21 -22 2015年03月 [無し][無し]
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    北澤 理子, 水野 洋輔, 北澤 荘平 日本病理学会会誌 104 (1) 206 -206 2015年03月 [無し][無し]
  • 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
    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]
  • 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, 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]
  • 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, 北澤 荘平 日本病理学会会誌 104 (1) 515 -515 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]
  • 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
    西 祐貴子, 北澤 理子, 北澤 荘平 日本病理学会会誌 104 (1) 528 -528 2015年03月 [無し][無し]
  • Padlock probeと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 104 (1) 529 -529 2015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 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]
  • 秋田 聡, 谷川 和史, 末廣 和長, 佐藤 元通, 喜安 佳人, 北澤 理子, 北澤 荘平, 渡部 祐司 日本臨床外科学会雑誌 75 (12) 3300 -3304 2014年12月 [無し][無し]
     
    S状結腸重複症による穿孔性腹膜炎の稀な症例を経験した.症例は81歳,男性.1年前から切除不能肺癌で対症療法を受けていた.腹痛を主訴として来院し,保存的治療を行うも増悪した.CT撮影を行い,骨盤内嚢胞と腹腔内遊離ガスを認め緊急手術を行った.膀胱壁に癒着したS状結腸に連続した嚢胞を認めた.嚢胞壁の小穿孔による限局性腹膜炎の所見であった.嚢胞をS状結腸と共に切除した.嚢胞とS状結腸は径5mmの瘻孔で交通し,嚢胞には便汁が充満していた.病理検査で嚢胞に腸粘膜を認め,重複腸管と診断した.消化管重複症は通常小児にみられる先天性疾患である.成人発症の大腸重複症は極めて稀である.成人の大腸重複症を文献的に検討し,臨床像を呈示する.(著者抄録)
  • 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
    西 祐貴子, 北澤 理子, 原口 竜摩, 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 87 -87 2014年09月 [無し][無し]
  • マウス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
    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]
  • 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性状解析(第一報)
    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]
  • 重症熱性血小板減少症候群(SFTS)の3剖検例
    北澤 理子, 水野 洋輔, 北澤 荘平 日本病理学会会誌 103 (2) 59 -59 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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    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 32回 251 -251 2014年07月 [無し][無し]
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    米倉 由利子, 中井 健太郎, 後藤 俊介, 藤井 秀毅, 北澤 理子, 北澤 荘平, 西 慎一 日本腎臓学会誌 56 (3) 337 -337 2014年05月 [無し][無し]
  • 重症熱性血小板減少症候群(SFTS)の一剖検例
    北澤 理子, 小黒 邦彦, 橘 さやか, 鶴岡 高志, 北澤 荘平 日本病理学会会誌 103 (1) 207 -207 2014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, 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]
  • 深部嚢胞胃炎に併発した胃癌におけるKCNE2の選択的発現低下についての検討
    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]
  • 有機溶媒と高血糖を背景とする多系統萎縮症の一剖検例
    永井 由紗, 北澤 理子, 近藤 武史, 原口 竜摩, 北澤 荘平 日本病理学会会誌 103 (1) 405 -405 2014年03月 [無し][無し]
  • 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]
  • 皮膚疣状黄色腫の免疫組織化学的検討
    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]
  • Identification and analysis of function of a novel splicing variant of receptor activator of NF-kB
    Riko Kitazawa, Ryuma Haraguchi, Yosuke Mizuno, Sohei Kitazawa JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 29 S285 -S285 2014年02月 [無し][無し]
  • 有機溶剤と高血糖が関与したと思われる多系統萎縮症の一剖検例
    永井 由紗, 藤石 琴, 北澤 理子, 北澤 荘平 日本毒性病理学会講演要旨集 30回 70 -70 2014年01月 [無し][無し]
  • 耳下腺原発DLBCLの治療中にMYD88遺伝子のL265P変異を生じた一症例
    藤石 琴, 永井 由紗, 北澤 理子, 北澤 荘平 日本毒性病理学会講演要旨集 30回 77 -77 2014年01月 [無し][無し]
  • Wnt/β-カテニンシグナルを基軸とする子宮発生メカニズムについての解析
    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]
  • 胃癌におけつCDX2遺伝子のメチル化メモリー現象とMUC2の発現について(Reactivation of CDX2 without loss of promoter hypermethylation in gastric cancer as mark for gene silencing memory)
    亀岡 祐里, 北澤 理子, 有安 奏, 立花 亮祐, 原口 竜摩, 北澤 荘平 日本癌学会総会記事 72回 303 -303 2013年10月 [無し][無し]
  • エピジェネティック因子の組織細胞化学 DNAメチル化部位検出の形態学への展開
    北澤 荘平, 原口 竜摩, 北澤 理子 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 39 -39 2013年09月 [無し][無し]
  • Padlock probeとhyperbranching rolling circle amplification(H-RCA)法を用いた病理組織切片上でのp16遺伝子プロモータ領域メチル化検出法
    二宮 鴻介, 北澤 荘平, 沖田 将慶, 菊澤 里佳子, 伊藤 才季, 原口 竜摩, 北澤 理子 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 62 -62 2013年09月 [無し][無し]
  • 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
    沖田 将慶, 北澤 理子, 二宮 鴻介, 菊澤 理佳子, 伊藤 才季, 原口 竜摩, 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 62 -62 2013年09月 [無し][無し]
  • 悪性リンパ腫におけるBob.1遺伝子発現不活化・再活性化の分子病理学的検討
    渡部 貴文, 北澤 理子, 伊藤 千尋, 桑原 奈都美, 原口 竜摩, 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 64 -64 2013年09月 [無し][無し]
  • 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]
  • 経静脈的に輸注されたWT1特異的人工CTLは腎糸球体たこ足細胞を傷害しない
    朝井 洋晶, 藤原 弘, 越智 史博, 峰野 純一, 岡本 幸子, 葛島 清隆, 池田 裕明, 北澤 荘平, 赤塚 美樹, 珠玖 洋, 安川 正貴 日本がん免疫学会総会プログラム・抄録集 17回 84 -84 2013年07月 [無し][無し]
  • ビタミンDはNrf2-Keap1経路を介して酸化ストレスを抑制し糖尿病性腎症の進展を抑制する
    中井 健太郎, 藤井 秀毅, 河野 圭志, 後藤 俊介, 北澤 理子, 北澤 荘平, 平田 道則, 篠原 雅巳, 深川 雅史, 西 慎一 日本腎臓学会誌 55 (3) 350 -350 2013年04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]
  • 甲状腺原発MYD88遺伝子変異陰性型DLBCLの一剖検例
    西 祐貴子, 河南 幸乃, 立花 亮祐, 原口 竜馬, 北澤 理子, 北澤 荘平 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]
  • マキサカルシトールは酸化ストレスを抑制し、2型糖尿病における腎障害進展を抑制する
    中井 健太郎, 藤井 秀毅, 河野 圭志, 後藤 俊介, 西 慎一, 平田 道則, 篠原 雅巳, 北澤 理子, 北澤 荘平, 深川 雅史 腎と骨代謝 25 (4) 342 -342 2012年10月 [無し][無し]
  • 2型糖尿病における早期血管病変に対するマキサカルシトールの効果
    河野 圭志, 藤井 秀毅, 中井 健太郎, 後藤 俊介, 深川 雅史, 西 愼一, 篠原 雅巳, 平田 道則, 北澤 理子, 北澤 荘平 腎と骨代謝 25 (4) 342 -343 2012年10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]
  • CREB1変異による新規多発奇形症候群剖検例の分子病態解析
    北澤 荘平, 近藤 武史, 森 清, 北澤 理子 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]
  • 骨髄移植後約10年後にGVHDによると思われる器質化肺炎をきたし死亡した1剖検例
    坂本 明優, 倉田 美恵, 北澤 荘平, 山本 耕一郎, 片山 均, 金子 政彦, 宮崎 龍彦, 増本 純也 日本病理学会会誌 101 (2) 58 -58 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]
  • EFFECT OF VITAMIN D ON VASCULAR LESIONS AND OXIDATIVE STRESS AT EARLY STAGE OF DIABETIC NEPHROPATHY
    Hideki Fujii, Hideki Fujii, Keiji Kono, Kentaro Nakai, Shunsuke Goto, Michinori Hirata, Masami Shinohara, Riko Kitazawa, Sohei Kitazawa, Masafumi Fukagawa, Shinichi Nishi NEPHROLOGY DIALYSIS TRANSPLANTATION 研究発表ペーパー・要旨(国際会議) 27 146 -146 2012年05月 [無し][無し]
  • 2型糖尿病における大動脈病変に対するビタミンDの効果
    河野 圭志, 藤井 秀毅, 中井 健太郎, 後藤 俊介, 篠原 雅巳, 平田 道則, 北澤 理子, 北澤 荘平, 深川 雅史, 西 愼一 日本腎臓学会誌 54 (3) 325 -325 2012年04月 [無し][無し]
  • Progranulin(PGRN); インスリン抵抗性を誘導する新規アディポカイン
    松原 稔哉, 三田 綾子, 南 幸太郎, 細岡 哲也, 北澤 荘平, 高橋 健一, 田守 義和, 横井 伯英, 西村 紀, 清野 進 糖尿病 55 (Suppl.1) S -114 2012年04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]
  • 北澤 荘平, 近藤 武史, 中川 みく, 藤石 琴, 原口 竜摩, 北澤 理子 検査と技術 40 (1) 24 -29 2012年01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]
  • 胃小細胞癌の臨床病理学的特徴について
    北澤 荘平 愛媛医学 30 (3) 167 -168 2011年09月 [無し][無し]
  • 急速な転帰を辿った胃癌による肺癌性リンパ管症及び多発性肺梗塞の1剖検症例
    狛 泰子, 松岡 弘典, 領家 永遠, 小山 美鳥, 福光 研介, 笠井 由隆, 桝屋 大輝, 吉松 昭和, 北澤 荘平, 鈴木 雄二郎 日本呼吸器学会雑誌 49 (8) 577 -582 2011年08月 [無し][無し]
     
    症例は58歳、女性。6週間以上持続する咳嗽のため当院紹介受診。胸部X線写真や胸部単純CT上、両側肺の浸潤影やすりガラス影を認め、精査加療目的で入院。気管支鏡検査等、種々の検査から診断はつかなかったが、CTにて縦隔、肺門、腹部に腫大リンパ節を認めたことから、悪性腫瘍の存在を疑い精査していたところ、第11病日、突然、高度の低酸素血症、血圧低下が出現した。検査所見より肺血栓塞栓症と診断して治療を開始したが第14病日永眠された。病理解剖の結果、胃癌及びそれによる肺癌性リンパ管症、更に、トルソー症候群を来たしていたと判明した。肺癌性リンパ管症が疑われたものの、急速に病状が悪化し難治性の肺血栓塞栓症によって死亡した症例を経験したので報告する。(著者抄録)
  • 急速な進行をみたGranulocyte colony stimulating factor産生子宮頸部扁平上皮癌の2症例
    藪田 真紀, 濱西 潤三, 佐藤 加苗, 佐藤 浩, 武内 享介, 北澤 荘平, 山田 重人, 濱西 正三 産婦人科の実際 60 (7) 1099 -1104 2011年07月 [無し][無し]
     
    閉経後出血などを主訴に来院となりGranulocyte-colony stimulating factor(G-CSF)産生子宮頸部上皮癌と診断された2症例(症例1:58歳・2経妊1経産、症例2:57歳・2経妊1経産)について報告した。その結果、両症例とも進行期IIb期であり、抗菌薬に抵抗性の発熱・白血球増多などの特徴的臨床症状を呈し、短期間に腫瘍の増大が認められた。手術による完全切除は困難と判断され、全身化学療法と放射線化学療法が施行されたが、初回治療から症例1は13ヵ月後、症例2は14ヵ月後に死亡となった。以上より、悪性腫瘍に発熱・白血球増多などの臨床症状を呈する場合はG-CSF産生腫瘍も念頭において診断と治療が必要と考えられた。
  • AP-1応答配列を介するRANK遺伝子発現制御機構の解析
    金藤 聡美, 北澤 理子, 石井 淳子, 近藤 武史, 森 清, 北澤 荘平 日本骨代謝学会学術集会プログラム抄録集 29回 226 -226 2011年07月 [無し][無し]
  • 糖尿病性骨病変に対するカルベジロールの効果
    後藤 俊介, 藤井 秀毅, 河野 圭志, 中井 健太郎, 濱田 康弘, 大和 英之, 篠原 雅巳, 北澤 理子, 北澤 荘平, 西 愼一, 深川 雅史 日本腎臓学会誌 53 (3) 405 -405 2011年05月 [無し][無し]
  • 新規アディポカインProgranulin(PGRN)の同定とインスリン抵抗性ならびに肥満における役割
    松原 稔哉, 三田 綾子, 南 幸太郎, 田守 義和, 北澤 荘平, 渡辺 真, 松尾 英一, 西村 紀, 清野 進 糖尿病 54 (Suppl.1) S -156 2011年04月 [無し][無し]
  • 新規アディポカインケマリンは耐糖能および褐色脂肪細胞機能を調節する
    高橋 裕, 高橋 路子, 置村 康彦, 井口 元三, 西沢 衡, 山本 雅昭, 隅田 健太郎, 藤本 和歌子, 北澤 理子, 北澤 荘平, 加治 秀介, 春日 雅人, 千原 和夫 糖尿病 54 (Suppl.1) S -157 2011年04月 [無し][無し]
  • 【病理診断に役立つ分子生物学】 (第1部)病理診断に役立つ分子生物学の手技と知識 DNAシークエンス
    北澤 荘平, 森 清, 近藤 武史, 北澤 理子 病理と臨床 29 (臨増) 16 -20 2011年04月 [無し][無し]
  • 筋芽細胞におけるTmem119の骨芽細胞分化促進機構について
    田中 賢一郎, 井上 喜文, 比佐 伊都子, 片桐 岳信, 北澤 理子, 北澤 荘平, 小守 壽文, 杉本 利嗣, 清野 進, 梶 博史 日本内分泌学会雑誌 87 (1) 267 -267 2011年04月 [無し][無し]
  • 高橋 路子, 置村 康彦, 井口 元三, 西澤 衡, 山本 雅昭, Handayaningsih Evi, 高橋 健一, Zolotaryov Fyodor, 洪 卿秀, 藤本 和歌子, 三木 隆司, 南 幸太郎, 北澤 理子, 北澤 荘平, 加治 秀介, 春日 雅人, 千原 和夫, 清野 進, 高橋 裕 日本内分泌学会雑誌 87 (1) 280 -280 2011年04月 [無し][無し]
  • PHOTO REPORT 陽子線治療を施行された膵頭部癌の1剖検例
    近藤 武史, 北澤 荘平 内科 107 (3) 540 -540 2011年03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, 金藤 聡美, 近藤 武史, 森 清, 北澤 荘平 日本病理学会会誌 100 (1) 314 -314 2011年03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]
  • AP-1応答配列を介するマウスRANK遺伝子発現制御機構の解析
    金藤 聡美, 北澤 理子, 石井 淳子, 近藤 武史, 森 清, 北澤 荘平 日本病理学会会誌 100 (1) 372 -372 2011年03月 [無し][無し]
  • PHOTO REPORT 薬剤の関与が疑われた慢性心筋炎の1剖検例
    近藤 武史, 森 清, 北澤 荘平 内科 107 (2) 337 -337 2011年02月 [無し][無し]
  • Photo Report HHMを示した髄外性形質細胞腫の1剖検例
    近藤 武史, 北澤 理子, 北澤 荘平 内科 107 (1) 154 -154 2011年01月 [無し][無し]
  • 延命処置による心筋壊死と心筋梗塞との鑑別
    森川 公子, 長崎 靖, 北澤 荘平, 森近 舞, 上野 易弘, 川嶋 隆久, 石井 昇 日本法医学雑誌 64 (2) 165 -166 2010年12月 [無し][無し]
  • 胆嚢大細胞神経内分泌細胞癌の1剖検例
    近藤 武史, 北澤 荘平 内科 106 (3) 570 -570 2010年09月 [無し][無し]
  • PHOTO REPORT 心タンポナーデにいたった甲状腺未分化癌の1剖検例
    近藤 武史, 北澤 荘平, 廣川 満良 内科 106 (2) 334 -334 2010年08月 [無し][無し]
  • STZ誘発糖尿病モデルラットにおける腎腫瘍発生初期におけるエピジェネティク変化の解析(Epigenetic event in early phase of renal tumorigenesis in rat STZ-induced diabetes model)
    北澤 荘平, 森 清, 近藤 武史, 北澤 理子 日本癌学会総会記事 69回 43 -43 2010年08月 [無し][無し]
  • RANKLはNFATを介して受容体RANK発現を正に制御する
    北澤 理子, 石井 淳子, 近藤 武史, 森 清, 北澤 荘平 日本骨代謝学会学術集会プログラム抄録集 28回 191 -191 2010年07月 [無し][無し]
  • 糖尿病性骨代謝異常におけるシンバスタチンの効果 糖尿病性骨代謝異常における酸化ストレスの関与について
    濱田 康弘, 北澤 理子, 北澤 荘平, 深川 雅史 日本骨代謝学会学術集会プログラム抄録集 28回 231 -231 2010年07月 [無し][無し]
  • CizによるRANKLのプロモーター制御機構の解析
    羽田 佑, 中元 哲也, 佐久間 朋美, 長尾 雅史, 早田 匡芳, 江面 陽一, 北澤 理子, 北澤 荘平, 野田 政樹 日本骨代謝学会学術集会プログラム抄録集 28回 266 -266 2010年07月 [無し][無し]
  • 病理診断・再生医療と組織化学法 エピジェネティクスと病理組織学的変化
    北澤 荘平, 森 清, 近藤 武史, 北澤 理子 組織細胞化学 2010 205 -214 2010年07月 [無し][無し]
  • RANKL UPREGULATES MOUSE RANK GENE TRANSCRIPTION THROUGH THE NFAT BINDING SITE OF RANK GENE PROMOTER
    R. Kitazawa, J. Ishii, S. Mukai, T. Kondo, M. Mori, K. Mori, S. Kitazawa OSTEOPOROSIS INTERNATIONAL 研究発表ペーパー・要旨(国際会議) 21 9 -10 2010年05月 [無し][無し]
  • DEREPRESSION OF MOUSE SFRP-4 GENE EXPRESSION BY OXIDATIVE STRESS: A PLAUSIBLE MECHANISM LEADING TO LOW-TURNOVER OSTEOPOROSIS IN DIABETES AND SENESCENCE
    K. Mori, R. Kitazawa, T. Kondo, S. Mukai, M. Mori, Y. Hamada, S. Kitazawa OSTEOPOROSIS INTERNATIONAL 研究発表ペーパー・要旨(国際会議) 21 294 -294 2010年05月 [無し][無し]
  • Novel parathyroid hormone-responsive Smad3-related factor, Tmem119, promotes osteoblast differentiation
    Itoko Hisa, Yoshifumi Inoue, Lucie Canaff, Geoffrey N. Hendy, Riko Kitazawa, Sohei Kitazawa, Toshihisa Komori, Toshitsugu Sugimoto, Susumu Seino, Hiroshi Kaji ENDOCRINE JOURNAL 研究発表ペーパー・要旨(国際会議) 57 S325 -S325 2010年03月 [無し][無し]
  • Identification and functional analysis of a novel splicing variant of mouse RANK
    Satomi Mukai, Riko Kitazawa, Junko Ishii, Takeshi Kondo, Akihiro Hakozaki, Keisuke Horiuchi, Kiyoshi Mori, Sohei Kitazawa ENDOCRINE JOURNAL 研究発表ペーパー・要旨(国際会議) 57 S487 -S487 2010年03月 [無し][無し]
  • RANKL upregulates mouse RANK gene transcription through the NFAT binding site of RANK gene promoter
    Riko Kitazawa, Junko Ishii, Satomi Mukai, Takeshi Kondo, Kiyoshi Mori, Sohei Kitazawa ENDOCRINE JOURNAL 研究発表ペーパー・要旨(国際会議) 57 S346 -S346 2010年03月 [無し][無し]
  • 高橋 路子, 高橋 健一, Zolotaryov Fyodor, 洪 卿秀, 西沢 衡, Handayaningsih Evi, 山本 雅昭, 古賀 大輔, 赤松 優, 三宅 一彰, 藤本 和歌子, 三木 隆司, 南 幸太郎, 北澤 理子, 北澤 荘平, 井口 元三, 置村 康彦, 加治 秀介, 春日 雅人, 清野 進, 千原 和夫, 高橋 裕 日本内分泌学会雑誌 86 (1) 155 -155 2010年03月 [無し][無し]
  • ラット酸化的ストレスモデルにおける腎腫瘍発生初期に生じるエピジェネティクス変化の解析
    北澤 荘平, 森 清, 向井 智美, 近藤 武史, 北澤 理子 日本病理学会会誌 99 (1) 192 -192 2010年03月 [無し][無し]
  • 破骨細胞分化因子受容体RANKの新規splicing variantの分離とその機能解析
    向井 智美, 北澤 理子, 石井 淳子, 近藤 武史, 箱崎 彰裕, 堀内 圭輔, 森 清, 北澤 荘平 日本病理学会会誌 99 (1) 209 -209 2010年03月 [無し][無し]
  • 破骨細胞分化因子RANKLはNFATを介して受容体RANK発現を促進する
    北澤 理子, 石井 淳子, 向井 智美, 近藤 武史, 森 清, 北澤 荘平 日本病理学会会誌 99 (1) 209 -209 2010年03月 [無し][無し]
  • 高齢sFRP-4遺伝子欠損マウスにおける骨代謝形質の検討
    森 清, 北澤 理子, 近藤 武史, 向井 智美, 濱田 康弘, 北澤 荘平 日本病理学会会誌 99 (1) 209 -209 2010年03月 [無し][無し]
  • ホスホリパーゼCεは炎症と血管形成の増大を通してApcMinマウスの腸腫瘍形成を促進する
    枝松 裕紀, 李 明珍, 北澤 理子, 北澤 荘平, 片岡 徹 日本生化学会大会プログラム・講演要旨集 82回 4T8p -3 2009年09月 [無し][無し]
  • 多彩な合併症を呈したNetherton症候群の1剖検例
    近藤 武史, 北澤 理子, 榎木 英介, 森 清, 長野 徹, 竹島 泰弘, 北澤 荘平 診断病理 26 (3) 186 -190 2009年07月 [無し][無し]
     
    Netherton症候群はSPINK5の変異により皮膚のバリア機能が著明に低下する常染色体劣性の疾患である。今回私共は多彩な合併症を呈したNetherton症候群の1剖検例を経験したので報告する。症例は10代前半女性。出生後より敗血症を反復し、肝外門脈閉塞症による門脈圧亢進症も認めた。末期には低栄養状態が進行し死亡に至った。解剖時には全身に魚鱗癬様紅皮症を認めた。前頭葉中心の脳萎縮があり、両側大脳基底核に石灰化が見られた。門脈には右枝の閉塞、側副血行路の発達、反復する血栓形成を認めた。(著者抄録)
  • PTH及びSmad3シグナルにより誘導される新規因子Tmem119は骨芽細胞の分化を促進する
    比佐 伊都子, 井上 喜文, カナフ・ルーシー, ヘンディ・ジェフリー, 北澤 理子, 北澤 荘平, 杉本 利嗣, 清野 進, 梶 博史 日本骨代謝学会学術集会プログラム抄録集 27回 160 -160 2009年07月 [無し][無し]
  • RANKLはNFATを介してマウスRANK遺伝子発現を促進する
    北澤 理子, 石井 淳子, 向井 智美, 近藤 武史, 森 清, 北澤 荘平 日本骨代謝学会学術集会プログラム抄録集 27回 209 -209 2009年07月 [無し][無し]
  • マウスRANKの新規splicing variantの分離とその機能解析
    向井 智美, 北澤 理子, 近藤 武史, 森 清, 田尻 美知子, 石井 淳子, 北澤 荘平 日本骨代謝学会学術集会プログラム抄録集 27回 229 -229 2009年07月 [無し][無し]
  • 糖化最終産物受容体(RAGE)欠損の骨代謝異常における酸化ストレスの役割 糖化最終産物受容体(RAGE)ノックアウトマウスを用いた検討
    濱田 康弘, 北澤 理子, 北澤 荘平, 深川 雅史 日本骨代謝学会学術集会プログラム抄録集 27回 273 -273 2009年07月 [無し][無し]
  • インスリン抵抗性と炎症 アディポサイエンスの臨床応用の視点から 新規アディポカイン、ケマリンの新たな機能 MafAを介して膵β細胞機能を調節し糖尿病発症と関連する
    高橋 裕, 高橋 路子, 西沢 衡, Handayaningsih Evi, 山本 雅昭, 高橋 健一, Fyodor Zolotaryov, 洪 卿秀, 藤本 和歌子, 三木 隆司, 南 幸太郎, 三宅 一彰, 北澤 理子, 北澤 荘平, 置村 康彦, 加治 秀介, 春日 雅人, 清野 進, 千原 和夫 糖尿病 52 (Suppl.1) S -27 2009年04月 [無し][無し]
  • 新規アディポカイン、ケマリンは膵β細胞機能を調節し、2型糖尿病患者においてその血中濃度が低下している
    高橋 路子, 西澤 衡, Handayaningsih Evi, 山本 雅昭, 古賀 大輔, 赤松 優, 猪俣 純枝, 藤本 和歌子, 三木 隆司, 南 幸太郎, 三宅 一彰, 北澤 理子, 北澤 荘平, 置村 康彦, 加治 秀介, 春日 雅人, 清野 進, 千原 和夫, 高橋 裕 糖尿病 52 (Suppl.1) S -227 2009年04月 [無し][無し]
  • 非肥満2型糖尿病モデルラット(SDTラット)における糖尿病性腎症進展のメカニズム
    藤井 秀毅, 濱田 康弘, 駒場 大峰, 北澤 理子, 北澤 荘平, 深川 雅史 日本腎臓学会誌 51 (3) 326 -326 2009年04月 [無し][無し]
  • 【骨関節病変のエッセンス 非腫瘍性病変】 骨代謝の基礎と骨粗鬆症の病態
    北澤 理子, 北澤 荘平 病理と臨床 27 (3) 225 -231 2009年03月 [無し][無し]
  • CYVADIC療法が奏効した肉腫型腹膜悪性中皮腫の1例
    草間 俊行, 小高 泰一, 常峰 紘子, 赤坂 浩司, 小泉 直樹, 藤本 康二, 坂野 茂, 伊藤 利江子, 近藤 武史, 北澤 荘平, 山村 倫子, 高橋 克仁 癌と化学療法 36 (3) 475 -478 2009年03月 [無し][無し]
     
    症例は66歳、女性。腹部膨満を主訴に2005年2月当院を受診した。検査上、炎症所見の上昇を認め、腹部CTにて腹腔内に巨大腫瘍を認めた。腹腔内腫瘍切除術、胃分節切除術、空腸切除術、横行結腸切除術、左卵巣嚢腫切除術および胃瘻設術を施行した。免疫組織染色により、肉腫型の腹膜悪性中皮腫と診断された。術後22日目より腫瘍の再増大を認めたため、cyclophosphamide(CPA)、vincristine(VCR)、adriamycin(ADM)およびdacarbazine(DTIC)を用いた多剤併用化学療法(CYVADIC療法)を施行した。2コース施行後の腹部CTにて腫瘍は著明に縮小していた。その後、paclitaxel(PTX)およびcarboplatin(CBDCA)静脈内投与を行ったが、腫瘍の急速な増大と汎発性血管内血液凝固症の併発のため術後132日目に死亡した。肉腫型悪性中皮腫は予後不良な疾患であるが、積極的に化学療法を行うことで予後の改善が期待される。(著者抄録)
  • 破骨細胞分化因子受容体RANKの新規splicing variantの分離とその機能解析
    向井 智美, 北澤 理子, 近藤 武史, 森 清, 田尻 美知子, 石井 淳子, 北澤 荘平 日本病理学会会誌 98 (1) 251 -251 2009年03月 [無し][無し]
  • マウスRANK遺伝子転写におけるNFATの機能解析
    北澤 理子, 石井 淳子, 向井 智美, 近藤 武史, 森 清, 北澤 荘平 日本病理学会会誌 98 (1) 251 -251 2009年03月 [無し][無し]
  • 扁平上皮、尿路上皮細胞間橋構造特異的単クローン抗体11B3の作成とその抗原の同定
    北澤 荘平, 近藤 武史, 櫛田 大輔, 森 清, 北澤 理子 日本病理学会会誌 98 (1) 346 -346 2009年03月 [無し][無し]
  • 胆嚢大細胞神経内分泌細胞癌(LCNEC)の1剖検例
    近藤 武史, 北澤 荘平, 榎木 英介, 森 清, 北澤 理子 日本病理学会会誌 98 (1) 353 -353 2009年03月 [無し][無し]
  • 遊離脂肪酸による転写因子SREBPを介するヒトElovl6の発現制御機構の解析
    田尻 美知子, 北澤 理子, 森 清, 向井 智美, 近藤 武史, 北澤 荘平 日本病理学会会誌 98 (1) 359 -359 2009年03月 [無し][無し]
  • sFRP-4遺伝子ノックアウトマウスにおける骨代謝形質の解析
    森 清, 北澤 理子, 近藤 武史, 濱田 康弘, 北澤 荘平 日本病理学会会誌 98 (1) 389 -389 2009年03月 [無し][無し]
  • マウスBAMBI遺伝子発現調節機構の解析
    近藤 武史, 北澤 理子, 森 清, 北澤 荘平 日本病理学会会誌 98 (1) 390 -390 2009年03月 [無し][無し]
  • 組織細胞化学に於ける転写解析 転写早期の新生mRNAの電子顕微鏡による動態解析
    北澤 荘平, 北澤 理子, 森 清, 近藤 武史 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 49回 40 -40 2008年10月 [無し][無し]
  • Lipopolysaccharide(LPS)は、転写因子PU.1、MITF抑制を介してRANK発現を抑制する
    北澤 理子, 石井 淳子, 森 清, 近藤 武史, 北澤 荘平 日本骨代謝学会学術集会プログラム抄録集 26回 155 -155 2008年10月 [無し][無し]
  • 生理的状態および糖尿病状態における糖化最終産物受容体(RAGE)の骨代謝へ及ぼす影響
    濱田 康弘, 北澤 理子, 北澤 荘平, 深川 雅史 日本骨代謝学会学術集会プログラム抄録集 26回 194 -194 2008年10月 [無し][無し]
  • Lipopolysaccharide Suppresses RANK Gene Through the Down-Regulation of PU.1 and MITF
    R. Kitazawa, J. Ishii, T. Kondo, K. Mori, K. P. McHugh, S. Kitazawa JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 23 S262 -S263 2008年09月 [無し][無し]
  • BAMBI Gene Is Epigenetically Silenced in a Subset of High-grade Bladder Cancer.
    S. Kitazawa, S. Sanda Khin, K. Mori, T. Kondo, R. Kitazawa JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 23 S302 -S302 2008年09月 [無し][無し]
  • PLCεによる小腸腺腫における腫瘍細胞の増殖と生存の制御(Regulation of tumor cell proliferation and survival in intestinal tumorigenesis by PLCε)
    李 明珍, 枝松 裕紀, 北澤 荘平, 片岡 徹 日本癌学会総会記事 67回 397 -397 2008年09月 [無し][無し]
  • 十二指腸陥凹型腺腫の2例
    藤尾 誓, 柏木 亮一, 田畑 文平, 清原 稔之, 北澤 荘平, 西上 隆之, 小嶋 高根 兵庫県医師会医学雑誌 51 (1) 37 -41 2008年09月 [無し][無し]
     
    症例1は70歳、男性。上部消化管内視鏡検査にて十二指腸下行部に径4mm大のII c様の陥凹型病変を認め、生検にて高度異型の管状腺腫と診断した。生検痕のため内視鏡的粘膜切除術(EMR)にて一括切除できず、分割切除となりアルゴンプラズマ凝固(APC)を追加した。症例2は69歳、女性。上部消化管内視鏡検査にて十二指腸下行部に径3mm大のII c様の陥凹型病変を認めた。症例1の経験に基づき生検は施行せず、EMRにて一括切除した。中等度異型の管状腺腫であった。(著者抄録)
  • 子宮頸部小細胞癌の1例
    佐久本 奈緒, 西川 裕子, 伊藤 利江子, 近藤 武史, 北澤 荘平 日本臨床細胞学会近畿連合会会誌 16 101 -102 2008年09月 [無し][無し]
  • 糖尿病性骨代謝異常における酸化ストレスの関与
    濱田 康弘, 藤井 秀毅, 駒場 大峰, 北澤 理子, 北澤 荘平, 深川 雅史 日本臨床分子医学会学術総会プログラム・抄録集 45回 76 -76 2008年07月 [無し][無し]
  • 北澤 荘平, 近藤 武史, 松田 修一, 森 清, 北澤 理子 臨床検査 52 (6) 655 -661 2008年06月 [無し][無し]
     
    「病的なメチル化」として検査対象になるものは,遺伝子発現との関連性のある特異的な部位におけるメチル化の状態である.そのなかでも特にCpG-islandのhypermethylationは,p16などの癌抑制遺伝子の不活化に関与することが報告されている.一方,技術的な側面からは病理で最も汎用性の高いホルマリン固定・パラフィン包埋検体を用いる場合,微量のDNAから検討せざるを得ないため,メチル化特異的PCR法の操作を効率良く行う工夫が必要となる.ここではわれわれが改良したアガロースビーズ法の概要を紹介し,結果の解釈の仕方や応用例を含め解説する.(著者抄録)
  • Paraovarian cystadenofibromaの1例
    舟木 馨, 福西 秀信, 北澤 理子, 北澤 荘平 診断病理 25 (2) 132 -135 2008年04月 [無し][無し]
     
    傍卵巣嚢腫は子宮附属器腫瘍性病変の一つであり、単胞性の嚢胞として認められるものが多い。嚢胞の内部に結節や隔壁などの構造を伴うものには腺腫、腺線維腫のほか、悪性腫瘍も含まれるが、悪性傍卵巣腫瘍の報告は極めて稀である。我々の経験した症例は、単房性嚢胞性腫瘤の内部に1ヶ所の充実性部分を有する腺線維腫であった。画像診断の進歩から、術前に傍卵巣嚢腫と診断される例も増えており、内部に充実性結節を有する腫瘍では術前に質的診断を得ることは困難のため、摘出後の病理標本により診断を確定する必要があると思われる。(著者抄録)
  • F2交配系を用いたSDTラットの糖尿病発症に関する量的形質遺伝子座解析およびコンジェニック系統による検証
    布施 雅規, 横井 伯英, 北澤 荘平, 北澤 理子, 篠原 雅巳, 清野 進 糖尿病 51 (Suppl.1) S -112 2008年04月 [無し][無し]
  • AST-120は酸化ストレスを抑制し、CKDにおける心病変の進展を抑制する
    藤井 秀毅, 後藤 澄江, 菅野 三喜男, 西島 冬彦, 大和 英之, 北澤 理子, 北澤 荘平, 深川 雅史 日本腎臓学会誌 50 (3) 289 -289 2008年04月 [無し][無し]
  • ナノワールドに於ける遺伝子産物動態 新生mRNAの動態解析
    北澤 荘平, 北澤 理子, 森 清, 近藤 武 解剖学雑誌 83 (Suppl.) 73 -73 2008年03月 [無し][無し]
  • 骨・関節疾患をめぐる最近の話題 破骨細胞分化の制御機構
    北澤 理子, 近藤 武史, 森 清, 石井 淳子, 北澤 荘平 日本病理学会会誌 97 (1) 145 -145 2008年03月 [無し][無し]
  • マウスBAMBI遺伝子発現調節機構の解析
    近藤 武史, 北澤 理子, 森 清, 北澤 荘平 日本病理学会会誌 97 (1) 241 -241 2008年03月 [無し][無し]
  • 急性期酸化的ストレスを介する骨吸収亢進メカニズムとマウスsFRP-4遺伝子発現再活性化機構の解析
    森 清, 北澤 理子, 近藤 武史, 濱田 康弘, 北澤 荘平 日本病理学会会誌 97 (1) 241 -241 2008年03月 [無し][無し]
  • 胃粘膜固有層の顆粒細胞腫に類似したマクロファージ集簇病変を来した一例
    森 清, 近藤 武史, 北澤 理子, 北澤 荘平 日本病理学会会誌 97 (1) 294 -294 2008年03月 [無し][無し]
  • 多彩な合併症を呈したNetherton症候群の1剖検例
    近藤 武史, 北澤 理子, 森 清, 北澤 荘平 日本病理学会会誌 97 (1) 313 -313 2008年03月 [無し][無し]
  • 膀胱癌進行におけるBAMBI遺伝子の後成的変化(Epigenetical alteration of BAMBI gene during bladder cancer progression)
    Sann Sanda Khin, 北澤 理子, Than Than Aye, Ne Win, 近藤 武史, 森 清, 北澤 荘平 日本病理学会会誌 97 (1) 343 -343 2008年03月 [無し][無し]
  • マウスRANK遺伝子プロモーターの解析
    石井 淳子, 北澤 理子, 近藤 武史, 森 清, 北澤 荘平 日本病理学会会誌 97 (1) 362 -362 2008年03月 [無し][無し]
  • 副腎腫瘍手術後に多発転移巣が出現した、副腎癌によるクッシング症候群の1剖検例
    田中 正巳, 石井 均, 水口 正義, 竹井 清純, 北澤 荘平 ACTH RELATED PEPTIDES 19 88 -90 2008年03月 [無し][無し]
  • 多様化する骨粗鬆症研究 糖尿病性骨減少症における酸化ストレスの関与 チオレドキシン1トランスジェニックマウスを用いた検討
    濱田 康弘, 藤井 秀毅, 北澤 理子, 北澤 荘平, 深川 雅史 Osteoporosis Japan 15 (Suppl.1) 103 -103 2007年10月 [無し][無し]
  • Thioredoxin-1 overexpression attenuates streptozotocin-induced diabetic Osteopenia in mice: A novel role of oxidative stress and therapeutic implications.
    Y. Hamada, H. Fujii, R. Kitazawa, S. Kitazawa, M. Fukagawa JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 22 S133 -S133 2007年09月 [無し][無し]
  • Comprehensive analysis of bone-related genes expression induced by acute oxidative stress
    K. Mori, R. Kitazawa, T. Kondo, Y. Hamada, S. Kitazawa JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 22 S467 -S467 2007年09月 [無し][無し]
  • Regulation of mouse BAMBI gene expression
    T. Kondo, R. Kitazawa, K. Mori, S. Kitazawa JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 22 S390 -S390 2007年09月 [無し][無し]
  • Thioredoxin-1 overexpression attenuates streptozotocin-induced diabetic osteopenia in mice: A novel role of oxidative stress and therapeutic implications
    Y. Hamada, H. Fujii, R. Kitazawa, S. Kitazawa, M. Fukagawa JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 22 S89 -S89 2007年09月 [無し][無し]
  • Molecular cloning and characterization of mouse RANK gene promoter region
    J. Ishii, R. Kitazawa, T. Kondo, K. Mori, K. P. McHugh, S. Kitazawa JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 22 S152 -S152 2007年09月 [無し][無し]
  • Modulation of mouse RANKL gene expression by runx2 and vitamin D3
    R. Kitazawa, K. Mori, T. Kondo, S. Kitazawa JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 22 S62 -S62 2007年09月 [無し][無し]
  • 子宮筋腫の新たな治療法
    北澤 荘平 病理と臨床 25 (8) 818 -819 2007年08月 [無し][無し]
  • Apc1Min誘導性発癌におけるRas/RapエフェクターのホスホリパーゼCepsilonの関与(Involvement of the Ras/Rap effector, phospholipase Cepsilon, in Apc1Min-induced tumorigenesis)
    李 明珍, 枝松 裕紀, 北澤 荘平, 片岡 徹 日本癌学会総会記事 66回 83 -83 2007年08月 [無し][無し]
  • 日本とミャンマーにおける膀胱腫瘍進展過程におけるBAMBI遺伝子のエピジェネティクス制御の変化(Epigenetical alteration of BAMBI gene during bladder cancer progression: comparison between Japan and Myanmar)
    キン・サン・サンダ, 北澤 理子, 近藤 武史, 森 清, エイ・タンタン, ウイン・ネ, 北澤 荘平 日本癌学会総会記事 66回 317 -317 2007年08月 [無し][無し]
  • 短期間酸化的ストレスによる骨代謝関連遺伝子発現の網羅的解析(Comprehensive Analysis of Bone-related Genes Expression Induced by Short-term Oxidative Stress)
    森 清, 北澤 理子, 近藤 武史, 濱田 康弘, 北澤 荘平 日本癌学会総会記事 66回 480 -480 2007年08月 [無し][無し]
  • マウスBAMBI遺伝子発現調節機構(Regulation of Mouse BAMBI Gene Expression)
    近藤 武史, 北澤 理子, 森 清, 北澤 荘平 日本癌学会総会記事 66回 504 -504 2007年08月 [無し][無し]
  • 肺癌剖検症例に対する肺内アスベスト小体濃度についての検討
    出射 由香, 釜田 里江, 松本 省司, 大西 一男, 北澤 理子, 北澤 荘平 日本職業・災害医学会会誌 55 (4) 165 -171 2007年07月 [無し][無し]
     
    [目的]肺癌剖検症例について肺内アスベスト小体計測検査を施行し、肺内アスベスト小体濃度と肺癌発症との関係について検討する。[対象と方法]平成8年1月から平成18年3月までの間に当院にて剖検を施行された肺癌症例24例について、肺内アスベスト小体濃度を測定した。また、症例の性別・年齢・肺癌の組織型・職種についても検討した。測定は平成17年12月に労働者健康福祉機構が開催したアスベスト小体計測検査講習会にて教示された神山らの方法に準じて行った。乾燥肺重量1gあたり5,000本以上のアスベスト小体が認められた症例(陽性症例)については胸部X線写真および胸部CTにてアスベスト肺・胸膜プラークの有無についても検討した。[結果]乾燥肺重量1gあたり5,000本以上のアスベスト小体が認められたのは2例(8.3%)、1,000本以上5,000本未満のアスベスト小体が認められたのは5例(20.8%)で、残り17例(70.8%)は1,000本未満であった。陽性症例2例とも職種については不明であった。陽性症例2例のうち1例はアスベスト肺・胸膜プラークともみられず、もう1例は胸膜プラークのみ確認された。[考察]アスベスト関連肺癌症例が肺癌全体の中に占める割合は低いと考えられたが、アスベスト関連肺癌患者総数が中皮腫患者数を上回る可能性を否定しえない。しかしその診断については画像診断のみでは困難なことも多いため、今後は複数の診療科医師が協力して行う必要があると考えられた。(著者抄録)
  • Runx2とvitamin D3による破骨細胞分化因子(RANKL)発現制御
    北澤 理子, 森 清, 近藤 武史, 北澤 荘平 日本骨代謝学会学術集会プログラム抄録集 25回 171 -171 2007年06月 [無し][無し]
  • マウスRANK遺伝子プロモーター領域の解析
    石井 淳子, 北澤 理子, 近藤 武史, 森 清, 北澤 荘平 日本骨代謝学会学術集会プログラム抄録集 25回 173 -173 2007年06月 [無し][無し]
  • マウスBAMBI遺伝子発現調節機構の解析
    近藤 武史, 北澤 理子, 森 清, 北澤 荘平 日本骨代謝学会学術集会プログラム抄録集 25回 188 -188 2007年06月 [無し][無し]
  • 抗酸化物質チオレドキシン1の糖尿病性骨減少症に及ぼす影響 チオレドキシン1トランスジェニックマウスを用いた検討
    濱田 康弘, 藤井 秀毅, 北澤 理子, 北澤 荘平, 深川 雅史 日本骨代謝学会学術集会プログラム抄録集 25回 191 -191 2007年06月 [無し][無し]
  • 急性期酸化的ストレスによる骨代謝関連遺伝子発現の網羅的解析
    森 清, 北澤 理子, 近藤 武史, 濱田 康弘, 北澤 荘平 日本骨代謝学会学術集会プログラム抄録集 25回 292 -292 2007年06月 [無し][無し]
  • 高橋 路子, 高橋 裕, 高橋 健一, Zolotaryov Fyodor N., 洪 卿秀, 飯田 啓二, 高橋 健太郎, 竹野 亮子, 福岡 秀規, 今中 真理, 西澤 衡, 加治 秀介, 置村 康彦, 清成 寛, 大島 尚子, 相澤 慎一, 北澤 理子, 北澤 荘平, 千原 和夫 日本内分泌学会雑誌 83 (1) 178 -178 2007年04月 [無し][無し]
  • アルコール性肝硬変患者に併発した国内発症急性E型肝炎の一剖検例
    森 清, 北澤 理子, 近藤 武史, 北澤 荘平 日本病理学会会誌 96 (1) 170 -170 2007年02月 [無し][無し]
  • 急性骨髄性白血病の同種骨髄移植に合併したVeno-occlusive disease(VOD)の1剖検例
    近藤 武史, 北澤 理子, 森 清, 北澤 荘平 日本病理学会会誌 96 (1) 170 -170 2007年02月 [無し][無し]
  • マウスRANK遺伝子プロモーターの解析
    石井 淳子, 北澤 理子, 近藤 武史, 北澤 荘平 日本病理学会会誌 96 (1) 216 -216 2007年02月 [無し][無し]
  • TATA-box近傍のCpGメチル化による破骨細胞分化因子(RANKL)転写抑制機構
    北澤 理子, 森 清, 近藤 武史, 北澤 荘平 日本病理学会会誌 96 (1) 216 -216 2007年02月 [無し][無し]
  • マウスBAMBI遺伝子発現調節機構の解析
    近藤 武史, 北澤 理子, 北澤 荘平 日本病理学会会誌 96 (1) 216 -216 2007年02月 [無し][無し]
  • 急性期酸化的ストレス下における骨代謝関連遺伝子発現の網羅的解析
    森 清, 北澤 理子, 近藤 武史, 濱田 康弘, 北澤 荘平 日本病理学会会誌 96 (1) 218 -218 2007年02月 [無し][無し]
  • 子宮平滑筋腫における集束超音波治療(FUS)抵抗性の機序
    北澤 荘平, 福西 秀信, 舟木 馨, 北澤 理子 日本病理学会会誌 96 (1) 253 -253 2007年02月 [無し][無し]
  • SOD-1遺伝子異常の証明された家族性筋萎縮性側索硬化症の一例
    藤本 昌代, 北澤 理子, 近藤 武史, 森 清, 北澤 荘平 日本病理学会会誌 96 (1) 263 -263 2007年02月 [無し][無し]
  • 日本、ミャンマー両国の膀胱腫瘍発生に関するエピェネティクス解析
    Sann Sanda Khin, 北澤 理子, 近藤 武史, 森 清, 北澤 荘平 日本病理学会会誌 96 (1) 302 -302 2007年02月 [無し][無し]
  • 肺癌剖検症例における肺内アスベスト小体濃度についての検討
    出射 由香, 松本 省司, 釜田 里江, 大西 一男, 北澤 理子, 北澤 荘平 日本病理学会会誌 96 (1) 343 -343 2007年02月 [無し][無し]
  • 悪性中皮腫剖検例の免疫組織化学による再検討
    兵頭 香織, 北澤 理子, 近藤 武史, 森 清, 北澤 荘平 日本病理学会会誌 96 (1) 357 -357 2007年02月 [無し][無し]
  • Regulation of osteoclastogenesis by CpG methylation of mouse receptor activator of NF-kappa B ligand (RANKL) gene promoter region.
    R. Kitazawa, K. Mori, T. Kondo, S. Kitazawa JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 21 S382 -S382 2006年09月 [無し][無し]
  • Modulation of mouse RANKL gene expression by Runx2 and the PKA pathway.
    K. Mori, R. Kitazawa, T. Kondo, A. Yamaguchi, S. Kitazawa JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 21 S383 -S383 2006年09月 [無し][無し]
  • Regulation of mouse BAMBI gene expression.
    T. Kondo, R. Kitazawa, S. Kitazawa JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 21 S252 -S252 2006年09月 [無し][無し]
  • 腎症-治療の実験的検討 タウリンの抗酸化作用による糖尿病性腎症進展抑制
    肥後 里実, 宮田 哲, 姜 青雲, 北澤 理子, 北澤 荘平, 春日 雅人 糖尿病合併症 20 (Suppl.1) 101 -101 2006年09月 [無し][無し]
  • PHOTO REPORT くも膜下出血で発症した左後頭蓋窩線維性髄膜腫
    近藤 武史, 北澤 理子, 北澤 荘平 内科 98 (2) 352 -352 2006年08月 [無し][無し]
  • マウスBAMBI遺伝子発現調節機構の解析
    近藤 武史, 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 24回 178 -178 2006年07月 [無し][無し]
  • ストレプトゾトシン誘発糖尿病マウスにおける骨病変は酸化ストレス亢進を伴った低回転骨である
    濱田 康弘, 河野 智子, 居, 北澤 理子, 北澤 荘平, 深川 雅史 日本骨代謝学会学術集会プログラム抄録集 24回 196 -196 2006年07月 [無し][無し]
  • TATA-box近傍のCpGメチル化による破骨細胞分化因子(RANKL)転写抑制機構
    北澤 理子, 森 清, 近藤 武史, 北澤 荘平 日本骨代謝学会学術集会プログラム抄録集 24回 207 -207 2006年07月 [無し][無し]
  • タウリンの糖尿病性腎症進展抑制効果と抗酸化作用
    肥後 里実, 宮田 哲, 姜 青雲, 北澤 理子, 北澤 荘平, 春日 雅人 糖尿病 49 (6) 484 -484 2006年06月 [無し][無し]
  • 【骨形成・骨吸収の最近のトピックス】 骨吸収・骨形成の相互作用 RANKL,OPGの転写制御
    北澤 荘平, 北澤 理子, 森 清, 近藤 武史 THE BONE 20 (3) 321 -326 2006年05月 [無し][無し]
     
    骨吸収因子の多くは,破骨細胞分化因子(RANKL),およびそのデコイレセプターであるOPGを最終標的としている.本稿では,主としてマウスRANKLおよびOPG遺伝子プロモータについての著者等の解析結果をもとに,RANKLおよびOPG遺伝子がどのように制御されているかについて説明する.特に,RANKL遺伝子の広範なクロマチンレベルでの構造変化とクロマチン構造の解離状態における種々の転写調節因子による発現制御機構についての知見を述べる(著者抄録)
  • 色素性乾皮症A群の一剖検例
    正木 太朗, 福永 瑞穂, 船坂 陽子, 錦織 千佳子, 北澤 理子, 北澤 荘平, 柿田 明美, 豊島 靖子, 市橋 正光 日本皮膚科学会雑誌 116 (5) 848 -848 2006年05月 [無し][無し]
  • 膵臓発癌中のDNMT1過発現による腫瘍関連遺伝子のDNAメチル化(DNA methylation of tumor-related genes with DNMT1 overexpression during pancreatic carcinogenesis)
    Peng DunFa, 金井 弥栄, 澤田 守男, 牛島 抄織, 平岡 伸介, 北澤 荘平, 広橋 説雄 日本病理学会会誌 95 (1) 190 -190 2006年04月 [無し][無し]
  • 頸管ポリープとして経過観察されていた子宮腺肉腫の1例
    近藤 武史, 北澤 理子, 山崎 正明, 北澤 荘平 診断病理 23 (2) 136 -139 2006年04月 [無し][無し]
     
    今回我々は,当初通常の頸管ポリープとして経過観察されていた子宮腺肉腫の手術症例を経験したので報告する.症例は50代女性で少量の不正性器出血を認め,近医受診,頸管ポリープを認めこれを切除された.以後数ヵ月ごとに頸管ポリープの再発および切除を繰り返していた.初診から半年後の切除検体で腺肉腫を疑われ,神鋼病院を紹介受診.準広汎子宮全摘術,左側付属器摘出術,リンパ節郭清術を施行された.組織学的検索の検果,同所性の腺肉腫と診断した.組織学的所見を中心に文献的考察を加えて日常診断上の注意点も含めて報告する(著者抄録)
  • パラフィン包埋試料を免疫原として作成した胚細胞特異的な単クローン抗体5G9が認識する抗原の解析
    北澤 荘平, 武中 篤, 溝口 明, 近藤 武史, 森 清, 藤本 昌代, 安松 良子, Sann Sanda Khin, 前田 盛, 北澤 理子 日本病理学会会誌 95 (1) 221 -221 2006年04月 [無し][無し]
  • 副腎皮質ホルモンによるマウス破骨細胞抑制因子(OPG)発現調節機構の解析
    近藤 武史, 北澤 理子, 山口 朗, 北澤 荘平 日本病理学会会誌 95 (1) 233 -233 2006年04月 [無し][無し]
  • Runx2とPKA経路によるマウスRANKL遺伝子発現調節機構の解析
    森 清, 北澤 理子, 近藤 武史, 前田 盛, 山口 朗, 北澤 荘平 日本病理学会会誌 95 (1) 233 -233 2006年04月 [無し][無し]
  • CpGメチル化による破骨細胞分化因子(RANKL)遺伝子発現制御機構
    北澤 理子, 北澤 荘平 日本病理学会会誌 95 (1) 233 -233 2006年04月 [無し][無し]
  • 心筋障害が顕著であったミトコンドリア脳筋症の一剖検例
    藤本 昌代, 北澤 荘平, 近藤 武史, 森 清, 北澤 理子, 前田 盛 日本病理学会会誌 95 (1) 320 -320 2006年04月 [無し][無し]
  • 陽子線治療を施行された膵頭部癌の一例
    近藤 武史, 北澤 理子, 藤本 昌代, 森 清, 前田 盛, 北澤 荘平 日本病理学会会誌 95 (1) 369 -369 2006年04月 [無し][無し]
  • 脊髄アスペルギルス症と脊髄癆を合併した統合失調症の1例
    近藤 武史, 北澤 理子, 三宅 雅人, 北澤 荘平 診断病理 23 (1) 52 -54 2006年01月 [無し][無し]
     
    脊髄アスペルギルス症と神経梅毒(脊髄癆)を合併した統合失調症の1剖検例を経験したので報告する.症例は60歳代男性で28歳時に統合失調症を発症し,長期間加療されていた.死亡の2ヵ月前より坐骨部痛を生じ,その後歩行不能になった.更に膀胱直腸障害・両下肢麻痺・左上肢麻痺などの多彩な神経症状が出現した.病理解剖により脊髄には馬尾を中心に真菌塊を認め,それに加え脊髄癆の組織変化を認めた.これらによる神経障害が末期の多彩な神経症状を惹起したものと考えられた(著者抄録)
  • 【臨床分子内分泌学 甲状腺・副甲状腺・骨内分泌代謝系】 BMPs 基礎研究の進展 BMP遺伝子発現調節
    北澤 荘平, 北澤 理子 日本臨床 63 (増刊10 臨床分子内分泌学(3)) 409 -413 2005年10月 [無し][無し]
  • Regulation of mouse osteoprotegerin gene expression by glucocorticoids.
    T Kondo, R Kitazawa, A Yamaguchi, S Kitazawa JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 20 (9) S311 -S311 2005年09月 [無し][無し]
  • Runx2 modulates RANKL expression by repressing its steady-state level in mouse osteoblastic/stromal cells.
    K Mori, R Kitazawa, T Kondo, A Yamaguchi, S Kitazawa JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 20 (9) S139 -S139 2005年09月 [無し][無し]
  • Mouse RANKL gene transcription is reversibly suppressed by CpG methylation of its promoter region.
    R Kitazawa, K Mori, T Kondo, S Kitazawa JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 20 (9) S138 -S138 2005年09月 [無し][無し]
  • 胚細胞および胚細胞由来腫瘍を認識する単クローン抗体5G9の認識する抗原解析
    北澤 荘平, 武中 篤, 北澤 理子, 近藤 武史, 前田 盛, 溝口 明 日本癌学会総会記事 64回 293 -293 2005年09月 [無し][無し]
  • S Kitazawa, R Kitazawa, C Obayashi, T Yamamoto JOURNAL OF BONE AND MINERAL RESEARCH 20 (8) 1472 -1477 2005年08月 [無し][無し]
     
    Introduction: Desmoid-type fibromatosis, originating from mesenchymal cells with myofibroblastic features, is a locally aggressive and frequently recurring infiltrative lesion. One such sporadic case with metaplastic ossification in the chest wall is presented. Materials and Methods: A 43-year-old man was referred to the hospital with a gradually enlarging hard mass in the left anterolateral chest wall. A thoracotomy was carried out, and histopathological specimens were used for immunohistochemical, genetic, and methylation studies. Results: Accumulation of altered P-catenin associated with a somatic heterozygous activating mutation in codon 41 was detected in the typical desmoid-type fibromatosis and at the ossifying focus. Among factors related to bone formation and the classical wnt-beta-catenin signaling pathway, BMP and activin membrane-bound inhibitor (BAMBI) expression was specifically downregulated at the ossifying focus. Hypermethylation of the BAMBI promoter was observed in microdissected tissue from the ossifying focus but not in that from the typical desmoid-type fibromatosis. Conclusions: Because both BMP and classical Wnt/beta-catenin/LEF1 signaling cooperatively and mutually induce differentiation of mesenchymal cells into osteoblastic cells and promote bone formation, the epigenetic event leading to the enhanced responsiveness to BMP signaling may play a crucial role in the formation of metaplastic bone.
  • 【新生児疾患】 Pena-Shokeir症候群I型の姉妹例
    柄川 剛, 親里 嘉展, 高寺 明弘, 片山 義規, 森沢 猛, 横山 直樹, 北澤 荘平, 松尾 雅文 小児科臨床 58 (8) 1719 -1724 2005年08月 [無し][無し]
     
    Pena-Shokeir症候群I型の姉妹例を経験した.姉は胎動の欠如,羊水過多,胎児水腫を指摘され胎児水腫が進行するため在胎30週に,妹も胎児水腫が出現し在胎28週に,ともに帝王切開にて出生した.姉妹ともに胎児MRIで肺低形成が疑われていた.出生時,二人とも全身の浮腫と多関節拘縮を認め,蘇生に反応せず生直後に死亡した.妹の病理所見で,脳回低形成,大脳皮質の神経細胞と脊髄前角細胞の減少,小脳低形成,肺低形成がみられた.本症候群の同胞例の報告は過去に12例みられるが,そのほとんどは肺低形成による胎児・早期新生児死亡である.前児がPena-Shokeir症候群I型の場合,妊娠早期からの厳重な観察,特にMRIによる胎児肺の評価が以後の管理・治療方針の決定に重要である(著者抄録)
  • 急速破壊性股関節症病態を示したオクロノーシス(組織黒変症)の1例
    近藤 武史, 北澤 理子, 長谷川 康裕, 北澤 荘平 診断病理 22 (3) 193 -195 2005年07月 [無し][無し]
     
    今回私共はオクロノーシスの1例を経験した.症例は70代女性,既往歴や家族歴には特記すべきことはない.4年前の頸椎症手術時に椎体終板が黒色であった.半年前より右股関節痛が生じ,その後急速に関節裂隙の狭小化を認め右変形性股関節症(急速進行性股関節症疑い)にて全人工股関節置換術を施行された.軟骨残存部は黒色であった.他の関節については,脊椎は強直性脊椎炎様の変化を示し両側膝関節も関節症であった.組織学的に鉄染色,マッソンフォンタナ染色共に陰性の黒褐色の沈着物を滑膜中心に認め,オクロノーシスと診断した(著者抄録)
  • Runx2はマウス骨芽細胞/間質細胞における破骨細胞分化因子(RANKL)発現を抑制的に調節する
    森 清, 北澤 理子, 近藤 武史, 山口 朗, 北澤 荘平 日本骨代謝学会学術集会プログラム抄録集 23回 176 -176 2005年06月 [無し][無し]
  • 多発性内分泌腺腫症I型及び続発性副甲状腺機能亢進症患者副甲状腺細胞におけるMeninの発現及び機能の検討
    梶 博史, 内藤 純子, 宗和 秀明, 北澤 理子, 北澤 荘平, 塚田 俊彦, 杉本 利嗣, 千原 和夫 日本骨代謝学会学術集会プログラム抄録集 23回 183 -183 2005年06月 [無し][無し]
  • 遺伝子プロモータ領域CpGメチル化による破骨細胞分化因子(RANKL)の転写抑制機構
    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 23回 188 -188 2005年06月 [無し][無し]
  • 副腎皮質ホルモンによるマウス破骨細胞抑制因子(OPG)発現調節機構の解析
    近藤 武史, 北澤 理子, 山口 朗, 北澤 荘平 日本骨代謝学会学術集会プログラム抄録集 23回 188 -188 2005年06月 [無し][無し]
  • 脳室上衣腫合併MEN1型の一例と副甲状腺におけるMeninの検討
    飛松 崇子, 梶 博史, 内藤 純子, 余 美慧, 宗和 秀明, 山内 美香, 塚田 俊彦, 北澤 理子, 北澤 荘平, 杉本 利嗣, 千原 和夫 日本内分泌学会雑誌 81 (Suppl.) 101 -103 2005年06月 [無し][無し]
     
    34歳男.3年前,左上肢の痺れ感を主訴に初診した.MRIで頸髄に髄内腫瘍を認めたため手術を行い,組織診断は脳室上衣腫であった.2年前,背部・心窩部痛が出現し,腹部CTで膵体部に1.4cm大の腫瘍を認めた.膵体部部分切除術を施行し,組織診断は内分泌腫瘍であった.今回,口渇,多飲,多尿が出現し精査入院となった.副甲状腺過形成と内分泌膵腫瘍を認め,MEN1(多発性内分泌腺腫症1型)と診断した.副甲状腺4腺摘出を行い,検査所見の改善が得られた.患者の副甲状腺組織についてMeninの発現・機能を調べたところ,不活性化されていることが示唆された
  • 抗酸化ストレス物質チオレドキシンの糖尿病性腎症に及ぼす効果
    濱田 康弘, 宮田 哲, 肥後 里実, 河野 智子, 居, 深川 雅史, 北澤 理子, 北澤 荘平, 春日 雅人 日本臨床分子医学会記録 41 44 -44 2005年05月 [無し][無し]
  • 肺梗塞を起こして死亡した潰瘍性大腸炎の1例
    藤本 昌代, 北澤 理子, 平田 健一, 山田 浩幸, 近藤 武史, 前田 盛, 北澤 荘平 診断病理 22 (2) 113 -116 2005年04月 [無し][無し]
     
    29歳男性,潰瘍性大腸炎の経過中に反復性肺血栓塞栓症による肺高血圧症が徐々に進行していたが,急性肺動脈血栓塞栓症にて短時間で死亡した.解剖時,潰瘍性大腸炎の炎症は慢性期の像であった.肺には新旧様々な血栓による肺動脈の閉塞所見や肺梗塞巣を認めた.潰瘍性大腸炎に合併する動静脈血栓塞栓症は稀だが,肺動脈血栓塞栓症は,病変の部位と大きさによっては致死的になりうるため注意を要する(著者抄録)
  • MEN1遺伝子の変異を同定できない乳癌合併MEN1症例におけるmeninの発現及び機能解析
    内藤 純子, 梶 博史, 宗和 秀明, 北澤 理子, 北澤 荘平, 塚田 俊彦, 小林 彰, 杉本 利嗣, 千原 和夫 日本内分泌学会雑誌 81 (1) 83 -83 2005年04月 [無し][無し]
  • 再生医学と病理 骨軟骨研究領域における再生医学の動向と病理学
    北澤 理子, 北澤 荘平 日本病理学会会誌 94 (1) 140 -140 2005年03月 [無し][無し]
  • DNAメチル化による破骨細胞分化因子(RANKL)発現制御
    北澤 理子, 北澤 荘平 日本病理学会会誌 94 (1) 197 -197 2005年03月 [無し][無し]
  • 単クローン抗体5G9の認識するヒト胚細胞特異抗原の解析
    北澤 荘平, 武中 篤, 北澤 理子, 近藤 武史, 溝口 明 日本病理学会会誌 94 (1) 210 -210 2005年03月 [無し][無し]
  • 11B3モノクローナル抗体を用いた種々の癌腫における免疫組織学的検討
    近藤 武史, 櫛田 大輔, 北澤 理子, 前田 盛, 北澤 荘平 日本病理学会会誌 94 (1) 233 -233 2005年03月 [無し][無し]
  • 胃底腺(腺頸部/体部腺)型の胃型腺腫は存在するのか
    九嶋 亮治, 八尾 隆史, 原田 大, 北澤 荘平, 岡部 英俊, 服部 隆則 日本病理学会会誌 94 (1) 257 -257 2005年03月 [無し][無し]
  • 副腎皮質ホルモンによるマウス破骨細胞抑制因子(OPG)発現調節機構の解析
    近藤 武史, 北澤 理子, 前田 盛, 北澤 荘平 日本病理学会会誌 94 (1) 277 -277 2005年03月 [無し][無し]
  • 異所骨形成を認めた胸壁デスモイド腫瘍の1症例
    北澤 荘平, 北澤 理子, 大林 千穂, 鹿股 直樹, 野田 尚子, 近藤 武史, 藤本 昌代, 森 清, 前田 盛, 山本 哲司 日本病理学会会誌 94 (1) 281 -281 2005年03月 [無し][無し]
  • 外陰部転移で発見されたmicropapillary componentを伴う甲状腺乳頭癌の1剖検例
    森 清, 北澤 理子, 近藤 武史, 鹿股 直樹, 前田 盛, 北澤 荘平 日本病理学会会誌 94 (1) 297 -297 2005年03月 [無し][無し]
  • レジオネラ感染症の2例
    藤本 昌代, 北澤 理子, 森 清, 安松 良子, 近藤 武史, 前田 盛, 北澤 荘平 日本病理学会会誌 94 (1) 381 -381 2005年03月 [無し][無し]
  • Pena-Shokeir症候群I型の1剖検例
    森 清, 北澤 理子, 近藤 武史, 岸本 健太, 前田 盛, 北澤 荘平 診断病理 22 (1) 64 -67 2005年01月 [無し][無し]
     
    Pena-Shokeir症候群I型の新生児の剖検例を報告する.脳梁欠損,脳回低形成,小脳低形成などの中枢神経系の異常に加え,特有の顔面奇形,四肢関節拘縮といった外表異常,全身筋萎縮,肺の低形成を認めた.組織学的には肺は気腔の形成が乏しく,中枢神経には,大脳皮質錐体細胞の減少傾向,脊髄前角細胞の変性を認めた.本症候群の発生機序は,神経又は筋原性の胎児運動低下あるいは欠如により関節や顔面の異常,筋萎縮,さらに,嚥下・呼吸様運動障害により肺低形成が起こるとされる.本例はPena-Shokeir症候群I型の典型例と考えられた(著者抄録)
  • 脳室上衣腫合併MEN1型の一例と副甲状腺におけるメニンの検討
    飛松 崇子, 梶 博史, 内藤 純子, 余 美慧, 宗和 秀明, 山内 美香, 塚田 俊彦, 北澤 理子, 北澤 荘平, 杉本 利嗣, 千原 和夫 日本内分泌学会雑誌 80 (3) 663 -663 2004年12月 [無し][無し]
  • Expression of mouse receptor activator of NF-kappa B ligand (RANKL) in growth plate and articular cartilage.
    K Kishimoto, R Kitazawa, A Darwanto, T Kondo, S Maeda, M Kurosaka, S Kitazawa JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 19 S115 -S115 2004年10月 [無し][無し]
  • Epigenetic regulation of mouse receptor activator NF-kappaB ligand (RANKL) gene
    R Kitazawa, K Mori, T Kondo, S Kitazawa JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 19 S411 -S411 2004年10月 [無し][無し]
  • Regulation of mouse osteoprotegerin gene expression by steroid hormones.
    T Kondo, R Kitazawa, S Maeda, S Kitazawa JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 19 S199 -S199 2004年10月 [無し][無し]
  • 硬組織ISH 破骨細胞分化因子(RANKL)発現局在について
    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 45回 45 -45 2004年10月 [無し][無し]
  • 鼻の巨細胞性線維芽細胞腫の1例
    近藤 武史, 北澤 荘平, 北澤 理子, 田口 孝爾 診断病理 21 (4) 300 -302 2004年10月 [無し][無し]
     
    70歳代男.1年ほどの間に小豆大の常色隆起性皮疹が鼻背部に出現,徐々に拡大し,径1.1cm,高さ1.0cmの隆起性皮疹を形成した.転移性皮膚癌を疑い全摘した.組織学的に病変の主座は真皮にあった.非腫瘍部との境界は不明瞭であり,粘液腫様基質を背景に紡錘形の線維芽細胞様細胞,単核また多核の巨細胞が疎に分布していた.粘液腫様基質はPAS染色およびアルシアン青染色に陰性であった.膠原線維の増生はごく軽度認めた.免疫組織化学的検索では線維芽細胞様細胞および巨細胞はCD34が陽性であり,EMA,S-100タンパク,desmin,α-smooth muscle actin,CD68(KP-1)などは陰性であった.MIB-1 indexは約1%であった.以上の組織学的特徴より,巨細胞性線維芽細胞腫と診断した.断端はごく一部で陽性であったが,術後8ヵ月で再発の兆候はない
  • DNAメチル化による破骨細胞分化因子(RANKL)発現制御
    北澤 理子, 北澤 荘平 日本癌学会総会記事 63回 400 -400 2004年09月 [無し][無し]
  • 11B3モノクローナル抗体を用いた種々の癌腫における免疫組織学的検討
    近藤 武史, 北澤 理子, 櫛田 大輔, 北澤 荘平 日本癌学会総会記事 63回 186 -187 2004年09月 [無し][無し]
  • 酸化ストレスと糖尿病性腎症進展との関係 抗酸化ストレス物質チオレドキシン過剰発現マウスの解析
    濱田 康弘, 宮田 哲, 肥後 里実, 河野 智子, 居, 深川 雅史, 北澤 理子, 北澤 荘平, 春日 雅人 糖尿病合併症 18 (Suppl.1) 56 -56 2004年09月 [無し][無し]
  • 成長軟骨と関節軟骨における破骨細胞分化因子(RANKL)の発現
    岸本 健太, 北澤 理子, Darwanto Agus, 近藤 武史, 前田 盛, 北澤 荘平 日本骨代謝学会学術集会プログラム抄録集 22回 99 -99 2004年08月 [無し][無し]
  • ステロイドホルモンによるマウス破骨細胞抑制因子(OPG)発現調節機構の解析
    近藤 武史, 北澤 理子, 前田 盛, 北澤 荘平 日本骨代謝学会学術集会プログラム抄録集 22回 114 -114 2004年08月 [無し][無し]
  • DNAメチル化による破骨細胞分化因子(RANKL)発現制御
    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 22回 190 -190 2004年08月 [無し][無し]
  • 抗酸化ストレス物質チオレドキシンの糖尿病性腎症に及ぼす効果
    濱田 康弘, 宮田 哲, 肥後 里実, 河野 智子, 居, 深川 雅史, 北澤 理子, 北澤 荘平, 春日 雅人 日本臨床分子医学会学術総会プログラム・抄録集 41回 46 -46 2004年07月 [無し][無し]
  • 膵癌及び大腸癌細胞株におけるTrkAの発現調節機構
    藤本 昌代, 北澤 理子, 前田 盛, 北澤 荘平 日本病理学会会誌 93 (1) 219 -219 2004年05月 [無し][無し]
  • ステロイドホルモンによるマウス破骨細胞抑制因子(OPG)発現調節機構の解析
    近藤 武史, 北澤 理子, 前田 盛, 北澤 荘平 日本病理学会会誌 93 (1) 242 -242 2004年05月 [無し][無し]
  • 感染症対応剖検施設の建築 安全性の観点から
    北澤 荘平, 北澤 理子, 近藤 武史, 仙波 秀峰, 横崎 宏, 前田 盛 日本病理学会会誌 93 (1) 323 -323 2004年05月 [無し][無し]
  • 感染症対応剖検施設の建築 教育重視の観点から
    北澤 理子, 北澤 荘平, 近藤 武史, 仙波 秀峰, 横崎 宏, 前田 盛 日本病理学会会誌 93 (1) 323 -323 2004年05月 [無し][無し]
  • Pena-Shokeir Syndrome Type Iの1剖検例
    森 清, 北澤 理子, 近藤 武史, 岸本 健太, 前田 盛, 北澤 荘平 日本病理学会会誌 93 (1) 365 -365 2004年05月 [無し][無し]
  • 【病理診断における分子生物学】 必要な基礎知識 転写因子
    北澤 荘平, 北澤 理子 病理と臨床 22 (増刊) 54 -58 2004年04月 [無し][無し]
  • 副甲状腺腫瘍におけるTGFβ及びmeninの役割 MEN1患者検体を用いた解析
    宗和 秀明, 梶 博史, 北澤 理子, 北澤 荘平, 飛松 崇子, 内藤 純子, 野村 利可子, 杉本 利嗣, 千原 和夫 日本内分泌学会雑誌 80 (1) 90 -90 2004年04月 [無し][無し]
  • 悪性腫瘍の骨破壊病変における遺伝子発現
    北澤 理子, 北澤 荘平 病理と臨床 22 (3) 285 -289 2004年03月 [無し][無し]
  • 精巣Mucinous adenocacinomaの1例
    玉田 博, 原田 健一, 武中 篤, 北澤 荘平 泌尿器科紀要 50 (2) 135 -135 2004年02月 [無し][無し]
  • 著明な全身の動脈硬化病変を有し,MRSAによる感染性大動脈瘤,細菌性心外膜炎を併発した一剖検例
    多和 秀人, 平田 健一, 井上 信孝, 川合 宏哉, 井内 陽子, 川嶋 成乃亮, 横山 光宏, 近藤 武史, 北澤 荘平, 前田 盛 Circulation Journal 67 (Suppl.III) 990 -990 2003年10月 [無し][無し]
  • アミオダロン加療中に間質性肺炎,薬剤性肝炎及び膵炎を伴った陳旧性心筋梗塞の1例
    小林 憲恭, 北澤 荘平, 北澤 理子, 近藤 武史, 藤本 昌代, 岸本 健太, 石田 達郎, 井上 信孝, 横山 光宏, 前田 盛 診断病理 20 (4) 328 -330 2003年10月 [無し][無し]
     
    67歳男.難治性心室頻拍に対しアミオダロン投与を開始したところ,投与開始16ヵ月目に甲状腺機能低下症,血清アミラーゼ高値が出現した.乾燥甲状腺末の投与とアミオダロンの減量にて軽快したが,19ヵ月目頃より乾性咳嗽が出現し,CTにて間質性肺炎を認めた.アミオダロンを中止し,ステロイドパルス療法を行い一旦軽快したが,慢性腎不全が増悪し,25ヵ月目に死亡した.病理解剖学的所見では,両側の上葉にはまだら状に肺胞中隔肥厚,膠原線維・線維芽細胞の増生,マッソン体の出現を認め,器質化肺炎型の高度な障害を示した.両側の下葉では更に高度な中隔の線維性肥厚が認められ,肺胞腔内にはマクロファージが充満しており,慢性間質性肺炎型の障害が著明であった.膵臓では膵管周囲に限局した線維化を認め,線維化部分周囲には軽度のリンパ球浸潤を認めた.膵管周囲の線維化は膵臓全体に一様にみられ,線維化の程度は膵管の太さに比例する傾向を認めた.肝臓にもグリソン鞘を中心とした線維化がみられた
  • Epigenetic regulation of mouse RANKL gene expression.
    S Kitazawa, A Darwanto, R Kitazawa JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 18 S74 -S74 2003年09月 [無し][無し]
  • Regulation of mouse osteoprotegerin gene expression by 1 alpha,25 dihydroxyvitamin D-3
    T Kondo, R Kitazawa, S Maeda, S Kitazawa JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 18 S30 -S30 2003年09月 [無し][無し]
  • Expression of mouse receptor of NF-kappaB ligand (RANKL) in growth plate and articular cartilage.
    K Kishimoto, R Kitazawa, A Darwanto, T Kondo, S Maeda, S Kitazawa JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 18 S190 -S190 2003年09月 [無し][無し]
  • Antiestrogens and mechanical loading both stimulate transcriptional activity of the BMP-6 promoter in osteoblasts in an ER alpha-dependent manner.
    DB Ong, HL Jessop, SM Colley, MR Norman, R Kitazawa, S Kitazawa, LE Lanyon, JH Tobias JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 18 S292 -S292 2003年09月 [無し][無し]
  • Functional elements for Transactivation by PTHrP are preserved in both human and mouse RANKL gene promoters.
    R Kitazawa, S Kitazawa JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 18 S223 -S223 2003年09月 [無し][無し]
  • Role of TGF-beta and menin in the proliferation and secretion of human parathyroid cells.
    H Sowa, H Kaji, R Kitazawa, S Kitazawa, T Tsukamoto, S Yano, GN Hendy, T Sugimoto, K Chihara JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 18 S43 -S43 2003年09月 [無し][無し]
  • マウス破骨細胞抑制因子(OPG)遺伝子発現調節機構の解析
    近藤 武史, 北澤 理子, 前田 盛, 北澤 荘平 日本癌学会総会記事 62回 84 -85 2003年08月 [無し][無し]
  • 胚細胞及び胚細胞由来腫瘍を認識する単クローン抗体5G9の作製とその抗原解析
    北澤 荘平, 武中 篤, 北澤 理子, 近藤 武史, 溝口 明 日本癌学会総会記事 62回 101 -101 2003年08月 [無し][無し]
  • 悪性腫瘍の溶骨性骨転移におけるRANKL発現制御機構
    北澤 理子, 北澤 荘平 日本癌学会総会記事 62回 166 -166 2003年08月 [無し][無し]
  • ラット睾丸の造精子過程におけるサイクリンD1発現,プロモータ領域のメチル化及びMeCP2発現の関連(Relationship Between Cyclin D1 Expression, Promoter Methylation and MeCP2 Expression in Rat Testis during Spermatogenesis)
    アグス・ダルワント, 北澤 理子, 北澤 荘平 日本癌学会総会記事 62回 386 -386 2003年08月 [無し][無し]
  • 膵癌及び大腸癌細胞株におけるTrkA発現の調節機構
    藤本 昌代, 北澤 理子, 前田 盛, 北澤 荘平 日本癌学会総会記事 62回 390 -390 2003年08月 [無し][無し]
  • ER alpha activates the BMP-6 promoter in bone and breast cells via distinct mechanisms
    DB Ong, SM Colley, MR Norman, R Kitazawa, S Kitazawa, JH Tobias JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 18 (7) 1364 -1364 2003年07月 [無し][無し]
  • 粘液腺癌成分及び平滑筋肉腫成分を含んだ大腸癌肉腫の1例
    佐々木 義之, 高橋 治海, 北澤 荘平 日本消化器外科学会雑誌 36 (7) 1063 -1063 2003年07月 [無し][無し]
  • 感染性大動脈瘤破綻による心タンポナーデの1例
    近藤 武史, 北澤 理子, 平田 健一, 北澤 荘平 診断病理 20 (3) 236 -238 2003年06月 [無し][無し]
     
    70代男.起立時の復視があり,内頸動脈狭窄を指摘された.虚血性心疾患の精査にて三枝病変を認めcoronary artery bypass graftingの適応と考えられたが,全身状態が悪化し,最終的には原因不明の急性心不全に陥り死亡した.経過中血液培養にてMRSAが検出されていたが感染巣は不明であった.剖検の結果,上行大動脈に感染性大動脈瘤を認め,心嚢腔への破綻による心タンポナーデをきたして死に至ったと考えられた
  • Becker型筋ジストロフィーの1剖検例
    近藤 武史, 北澤 理子, 和田 博子, 北澤 荘平 診断病理 20 (3) 283 -285 2003年06月 [無し][無し]
     
    50代男.下腿筋力低下,左前胸部不快感,労作時呼吸困難を自覚していた.精査の結果,Becker型筋ジストロフィー(ジストロフィン遺伝子exon 13の変異)と診断された.心不全に対する治療を受け軽快退院し,その後十年程経過観察されていたが,再び心不全が悪化した.頻発する不整脈(心室頻拍)に対してペーシングや植え込み型除細動器の植え込みなどを行うが,次第に心機能が悪化し死亡した.死亡直前に抗生剤を変更した際に,末硝血中の好酸球数が350/mm3から6400/mm3に上昇していた.この際,黄疸を含む肝機能障害や腎機能障害は認めていなかった.剖検の結果,心重量は730g,著明な心腔拡大と刺激伝導系を含む心筋全体に高度の線維化を認めた.免疫染色にて骨格筋細胞膜上では巣状のジストロフィン蛋白の分布が確認されたが,心筋では高度の変性・線維化により有意な所見は得られなかった.一方,好酸球増多症に対応する所見として心筋細胞間には著明な好酸球浸潤がみられた
  • 平野 雅嗣, 山崎 克人, 櫻井 孝, 近藤 威, 劉 嘉忠, 岡田 弘, 杉村 和朗, 北澤 荘平, 北澤 理子, 前田 盛, 片渕 哲朗, 田村 進一 医学物理 23 (2) 157 -159 2003年06月 [無し][無し]
     
    X線屈折コントラスト効果を利用した血管径計測アルゴリズムを開発し,ラット微小血管造影像における血管径計測実験によって精度を検証したので報告した.ROI内で計測対象血管横断位置は設定されているものとした.Spring-8,BL-20B2の単色X線でサチコンカメラ(1ピクセル約7μm)を用いて得られたラット脳血管造影動画のスチール画像を処理画像として用いた.その結果,積分時間(数十ms)が短く,画質が良いとは言えないが,明線効果を用いて目視測定結果とほぼ同等の結果が得られた.以上より,屈折コントラストは放射光を用いなくても微小光源を用いても観察され,又,卓上型の放射光源も開発中であることから,今後臨床にて適用可能と思われた
  • Regulation of mouse osteoprotegerin gene expression by steroid hormones
    T Kondo, R Kitazawa, S Maeda, S Kitazawa BONE 研究発表ペーパー・要旨(国際会議) 32 (5) S75 -S75 2003年05月 [無し][無し]
  • Structure and functional elements of human and mouse RANKL gene promoter
    R Kitazawa, K Kajimoto, T Kondo, S Kitazawa BONE 研究発表ペーパー・要旨(国際会議) 32 (5) S76 -S76 2003年05月 [無し][無し]
  • 「形態・機能と遺伝子」骨軟部腫瘍 悪性腫瘍の骨破壊病変における遺伝子発現
    北澤 理子, 北澤 荘平 日本病理学会会誌 92 (1) 152 -152 2003年04月 [無し][無し]
  • 膵癌及び大腸癌細胞株におけるTrkAの発現調節機構
    藤本 昌代, 北澤 理子, 前田 盛, 北澤 荘平 日本病理学会会誌 92 (1) 207 -207 2003年04月 [無し][無し]
  • ステロイドホルモンによるマウス破骨細胞抑制因子(OPG)発現調節機構の解析
    近藤 武史, 北澤 理子, 前田 盛, 北澤 荘平 日本病理学会会誌 92 (1) 224 -224 2003年04月 [無し][無し]
  • 成長軟骨と関節軟骨における破骨細胞分化因子(RANKL)の発現
    岸本 健太, 北澤 理子, アグス・ダルワント, 近藤 武史, 前田 盛, 北澤 荘平 日本病理学会会誌 92 (1) 228 -228 2003年04月 [無し][無し]
  • 脂肪肉腫への分化を示す肺癌肉腫の一剖検例
    北澤 理子, 北澤 荘平, 藤本 昌代, 近藤 武史, 前田 盛, 西村 善博, 大林 千穂 日本病理学会会誌 92 (1) 279 -279 2003年04月 [無し][無し]
  • 胚細胞及び胚細胞由来の腫瘍を認識する単クローン抗体5G9の作製及びその抗原解析
    北澤 荘平, 武中 篤, 近藤 武史, 北澤 理子 日本病理学会会誌 92 (1) 307 -307 2003年04月 [無し][無し]
  • 日本人におけるMatrix Gla Protein T-138C遺伝子多型の剖検症例よりの解析
    小林 憲恭, 北澤 理子, 前田 盛, 北澤 荘平 日本病理学会会誌 92 (1) 324 -324 2003年04月 [無し][無し]
  • 心筋緻密化障害の1例
    近藤 武史, 北澤 理子, 小林 憲恭, 北澤 荘平 日本病理学会会誌 92 (1) 328 -328 2003年04月 [無し][無し]
  • 肺梗塞で死亡した潰瘍性大腸炎の1例
    藤本 昌代, 北澤 荘平, 平田 健一, 山田 浩幸, 近藤 武史, 前田 盛, 北澤 理子 日本病理学会会誌 92 (1) 393 -393 2003年04月 [無し][無し]
  • 糸球体内転移を伴った膵悪性腫瘍の3例
    藤本 昌代, 北澤 理子, 近藤 武史, 前田 盛, 北澤 荘平 診断病理 20 (2) 144 -145 2003年04月 [無し][無し]
     
    悪性腫瘍の腎転移の中でも糸球体係蹄内への転移は比較的稀な病態である.今回私共は糸球体内転移をきたした膵悪性腫瘍の3例を経験したので,成因についての考察を加え報告する(著者抄録)
  • 大島 富太郎, 嶋田 安秀, 楠 信也, 岩谷 慶照, 宮崎 直之, 北澤 荘平 日本消化器外科学会雑誌 35 (12) 1821 -1825 2002年12月 [無し][無し]
     
    70歳女.強度な貧血の精査目的で入院した.注腸造影,上部消化管内視鏡検査,腹部CT,消化管出血シンチグラフィでは出血を疑わせる所見は認められなかった.大腸内視鏡検査で盲腸と回腸末端部に血液の貯留を認めたため,イレウスチューブ挿入後造影検査を行ったところ,小腸に類円形の陰影欠損が認められたことから,この病変が出血源であると判断して開腹手術を施行した.術中所見としてトライツ靱帯より約3m,回腸末端より約2.5mの小腸中央部に,漿膜と腸間膜移行部分に発赤を伴う軟らかい腫瘤を触知し,これを含めて小腸部分切除を行った.切除標本では大きさ15×15×8mm,弾性軟,亜有茎の腫瘍で,病理組織学的に毛細血管腫と診断した
  • 膵癌及び大腸癌細胞株におけるTrkAの発現調節機構
    藤本 昌代, 北澤 理子, 前田 盛, 北澤 荘平 日本癌学会総会記事 61回 131 -131 2002年10月 [無し][無し]
  • 副甲状腺ホルモン関連蛋白(PTHrP)による破骨細胞分化因子(RANKL)発現制御機構
    北澤 理子, 北澤 荘平 日本癌学会総会記事 61回 134 -134 2002年10月 [無し][無し]
  • マウス破骨細胞抑制因子(OPG)遺伝子発現調節機構の解析
    近藤 武史, 北澤 理子, 前田 盛, 北澤 荘平 日本癌学会総会記事 61回 268 -269 2002年10月 [無し][無し]
  • インドネシアにおける大腸癌症例のE-cadherin蛋白発現とpromoterのメチル化,MeCP2発現との関連
    Agus Darwanto, 北澤 理子, 前田 盛, 北澤 荘平 日本癌学会総会記事 61回 371 -371 2002年10月 [無し][無し]
  • 胚細胞に発現する29kD蛋白を認識する5G9単クローン抗体の樹立(Establishment of monoclonal antibody, 5G9, recognizing 29kD protein in germ cells)
    北澤 荘平, 近藤 武史, 北澤 理子 日本癌学会総会記事 61回 386 -386 2002年10月 [無し][無し]
  • エピジュネティクスによる遺伝子発現調節機構の解析 病理組織検体への展開
    北澤 荘平 日本病理学会会誌 91 (2) 18 -18 2002年10月 [無し][無し]
  • 肝細胞癌と細胆管細胞癌の合併した肝腫瘍の1剖検例
    金 永学, 北澤 理子, 近藤 武史, 北澤 荘平 診断病理 19 (4) 343 -345 2002年10月 [無し][無し]
     
    78歳男.主訴は食道静脈瘤からの出血.肝細胞癌と細胆管細胞癌の合併した肝腫瘍であり,剖検時にS2-3に存在した腫瘍組織は肝細胞癌の形態を示す成分を含んでいたが,大部分はbrush borderを有する小管腔構造を特徴とする細胆管細胞癌であった.細胆管細胞癌は細胆管又はHering管から発生すると考えられており,原発性肝癌の約1%を占める稀な組織型であった
  • Relationship between E-cadherin expression, promoter methylation and MeCP2 expression in colorectal carcinoma
    A Darwanto, R Kitazawa, S Maeda, S Kitazawa JOURNAL OF PATHOLOGY 研究発表ペーパー・要旨(国際会議) 198 40A -40A 2002年09月 [無し][無し]
  • PTHrP transactivates RANKL gene through PKA and PKC pathways on mouse stromal cells.
    R Kitazawa, S Kitazawa JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 17 S250 -S250 2002年09月 [無し][無し]
  • Regulation of mouse osteoprotegerin gene expression by steroid hormones
    T Kondo, R Kitazawa, S Maeda, S Kitazawa JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 17 S344 -S344 2002年09月 [無し][無し]
  • CpG methylation around transcription start site of RANKL gene controls its steady-state expression.
    S Kitazawa, R Kitazawa JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 17 S335 -S335 2002年09月 [無し][無し]
  • The oestrogen receptor activates BMP-6 in a non-ligand-dependent manner
    SM Colley, DB Ong, S Kitazawa, M Norman, D Wynick, JT Tobias JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 17 (7) 1331 -1331 2002年07月 [無し][無し]
  • 北澤 荘平, 近藤 武史, 北澤 理子 電子顕微鏡 37 (2) 89 -91 2002年07月 [無し][無し]
  • 子宮粘液性平滑筋肉腫(myxoid leiomyosarcoma)の1例
    近藤 武史, 北澤 理子, 前田 盛, 北澤 荘平 診断病理 19 (3) 247 -248 2002年07月 [無し][無し]
     
    47歳女.子宮筋腫の診断で子宮全摘術を施行された.子宮内容物は血性で,通常の子宮平滑筋腫様の結節と,ゼラチン様を呈する結節が認められた.組織所見では周囲組織に対して浸潤性に増生する腫瘍で,多量の粘液状物質の中に紡錘形細胞が散在性に認められた.核分裂像は強拡大10視野当たり平均1〜2個であった.組織学的所見より子宮の粘液性平滑筋肉腫と診断した.術後8ヵ月経過したが転移再発の徴候を認めていない
  • 森田 宗孝, 谷 聡, 萩原 良輔, 劉 嘉忠, 八木 規夫, 山下 順平, 今西 築, 北澤 荘平 日本消化器病学会雑誌 99 (4) 391 -396 2002年04月 [無し][無し]
     
    45歳女.腹痛を主訴とした.腹部造影CT,Gaシンチ所見から,腸間膜より発生した悪性リンパ腫を疑い,確定診断のため開腹生検を施行した.小腸間膜リンパ節の病理組織学的所見より,腸間膜原発のホジキン病と診断し,化学療法により完全寛解した.現在3年を経過するが,再発を認めていない.腸間膜原発のホジキン病は日本では極めて稀な疾患であるが,CT,Gaシンチが診断に役立ち,治療可能な疾患として,巨大腫瘤を形成しないうちに迅速な試験開腹が診断と治療に肝要であると考えられた
  • マウス骨折治癒過程におけるHeparanaseの発現局在
    西條 雅康, 北澤 理子, 中島 元夫, 前田 盛, 北澤 荘平 日本病理学会会誌 91 (1) 158 -158 2002年03月 [無し][無し]
  • 副甲状腺ホルモン関連蛋白(PTHrP)による破骨細胞分化因子(RANKL)発現制御機構
    北澤 理子, 北澤 荘平 日本病理学会会誌 91 (1) 176 -176 2002年03月 [無し][無し]
  • 1,25(OH)2 vitamin D3(Vit D3)によるマウス破骨細胞抑制因子(OPG)発現調節機構の解析
    近藤 武史, 北澤 理子, 前田 盛, 北澤 荘平 日本病理学会会誌 91 (1) 200 -200 2002年03月 [無し][無し]
  • 神経周囲浸潤を伴う膵癌におけるTrkAの発現
    藤本 昌代, 北澤 理子, 前田 盛, 北澤 荘平 日本病理学会会誌 91 (1) 310 -310 2002年03月 [無し][無し]
  • モノクローナル抗体(MAb)5G9により明らかにされた生殖細胞共通抗原(GCCA)(Germ Cell Common Antigen Defined by Monoclonal Antibody 5G9)
    北澤 荘平, 北澤 理子 日本病理学会会誌 91 (1) 328 -328 2002年03月 [無し][無し]
  • 大腸癌におけるE-カドヘリン遺伝子発現のepigenetical regulation(Epigenetical Regulation of E-cadherin Gene Expression in Colorectal Carcinoma)
    Agus Dawranto, 北澤 理子, 前田 盛, 北澤 荘平 日本病理学会会誌 91 (1) 210 -210 2002年03月 [無し][無し]
  • ヒト破骨細胞分化因子(RANKL)遺伝子の5'側上流領域の解析
    梶本 和義, 北澤 理子, 前田 盛, 北澤 荘平 日本病理学会会誌 91 (1) 200 -200 2002年03月 [無し][無し]
  • ヒトRANK ligand遺伝子の5'側上流領域の解析
    梶本 和義, 北澤 理子, 北澤 荘平 神戸大学医学部紀要 62 (3〜4) 143 -150 2002年03月 [無し][無し]
     
    1α,25(OH)2D3によるヒトReceptor Activator of NF-κB Ligand(RANKL)遺伝子の転写調節機構を詳細に解析するため,遺伝子5'側上流領域のクローニングを行った.1α,25(OH)2D3は破骨細胞形成を促進し,SaOS2細胞におけるRANKL mRNA発現を誘導した.ヒトRANKL遺伝子5'側上流領域には,基本転写調節部位に逆TATA,CAATボックス,Runx2結合配列,3ヶ所のvitamin D3結合配列(VDRE)類似配列を認めた.ゲルシフトアッセイにて3ヶ所のVDRE配列のうち最上流がVDR,RXRαヘテロダイマーとin vitroでの結合性を示し,核蛋白抽出物とステロイドホルモン受容体に対する抗体を用いたスーパーシフトアッセイでもVDR,RXRヘテロダイマーの結合が認められた.ヒト骨芽細胞SaOS2を用いた一過性遺伝子導入試験にて,1α,25(OH)2D3はVDREを有するRANKLプロモーターコンストラクトの転写活性を促進したが,VDRE欠失コンストラクトや変異VDRE組み込みコンストラクトでは有意な活性促進作用を示さなかった.以上より,ヒト骨芽細胞において1α,25(OH)2D3はRANKL遺伝子5'側上流領域に存在するVDREを介しRANKL遺伝子発現を転写レベルで促進し破骨細胞形成に寄与すると考えられた
  • 放射光による新しい病理イメージングの研究
    山崎 克人, 大林 千穂, 埴岡 啓介, 北澤 荘平, 北澤 理子, 前田 盛 病理と臨床 19 (11) 1251 -1256 2001年11月 [無し][無し]
  • 陰嚢疣贅状黄色腫(verruciform xanthoma)の1例
    近藤 武史, 北澤 理子, 金 永学, 前田 盛, 北澤 荘平 診断病理 18 (4) 417 -418 2001年10月 [無し][無し]
     
    70歳男.陰嚢に生じた疣贅状黄色腫で,陰嚢に1.5cm大の乳頭状隆起性病変が認められた.表皮は乳頭状に増生し,真皮にはfoamy macrophageの著明な増生を認められ,組織学的に陰嚢疣贅状黄色腫と診断された.免疫組織化学によりfoamy macrophageの集簇過程にマクロファージ走化因子の関与が示唆された
  • Regulation of mouse osteoprotegerin gene expression by 1,25 dihydroxyvitamin D-3.
    T Kondo, R Kitazawa, S Maeda, S Kitazawa JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 16 S208 -S208 2001年09月 [無し][無し]
  • Heparanase mRNA expression during fracture repair.
    M Saijo, R Kitzazawa, M Nakajima, S Maeda, S Kitazawa JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 16 S239 -S239 2001年09月 [無し][無し]
  • Characterization of 5 '-flanking region of human RANK ligand gene.
    K Kajimoto, R Kitazawa, S Maeda, S Kitazawa JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 16 S184 -S184 2001年09月 [無し][無し]
  • RANK ligand expression at bone metastatic sites of malignant tumor: Analysis of autopsy cases.
    R Kitazawa, S Kitazawa JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 16 S332 -S332 2001年09月 [無し][無し]
  • 副甲状腺細胞増殖能とカルシウム感知受容体及びビタミンD受容体の発現との関係を検討しえた高度二次性副甲状腺機能亢進症を呈した慢性腎不全の18例
    矢野 彰三, 杉本 利嗣, 塚本 達雄, 千原 和夫, 小林 彰, 北澤 荘平, 前田 盛, 北澤 理子 ホルモンと臨床 49 (秋季増刊) 90 -93 2001年09月 [無し][無し]
     
    二次性副甲状腺機能亢進症(A)で副甲状腺腫大が生じる機序を明らかにする目的で,重篤なAをきたした長期透析患者18例より摘除された副甲状腺を用いてCa感知受容体(CaSR),ビタミンD受容体(VDR)の発現と細胞増殖能との関係について検討した.その結果,増殖能の亢進している細胞ほどCaSR,VDRとも有意に発現が低下しており,両受容体が副甲状腫大に関わっている可能性が示唆された
  • 悪性腫瘍骨転移病巣における破骨細胞分化因子(RANKL)の発現
    北澤 理子, 北澤 荘平 日本癌学会総会記事 60回 445 -445 2001年09月 [無し][無し]
  • 神経周囲浸潤を伴う膵癌におけるTrkAの発現機構
    藤本 昌代, 北澤 理子, 前田 盛, 北澤 荘平 日本癌学会総会記事 60回 197 -197 2001年09月 [無し][無し]
  • 大腸癌におけるE-cadherin発現とプロモータ領域のメチル化,MeCP2発現との関連(Relationship between E-cadherin expression, promoter methylation and MeCP2 expression in colorectal carcinoma)
    Agus Darwanto, 北澤 理子, 前田 盛, 北澤 荘平 日本癌学会総会記事 60回 317 -317 2001年09月 [無し][無し]
  • 肺癌細胞株におけるPTHrP遺伝子CpGアイランドのメチル化とTGF-βによるpromoter usageの変化についての検討
    金 永学, 北澤 理子, 前田 盛, 北澤 荘平 日本癌学会総会記事 60回 509 -509 2001年09月 [無し][無し]
  • 正常リンパ組織及び悪性リンパ腫におけるTCL1発現
    井上 広之, 北澤 荘平, 北澤 理子, 前田 盛 日本癌学会総会記事 60回 351 -351 2001年09月 [無し][無し]
  • 悪性腫瘍骨転移病巣におけるRANKL/ODFの発現 病理解剖症例の解析
    北澤 理子, 北澤 荘平, 近藤 武史, 藤田 靖之, 藤田 義行, 前田 盛 日本骨代謝学会雑誌 19 (2) 141 -141 2001年07月 [無し][無し]
  • 骨折治癒過程におけるHeparanaseの発現
    西條 雅康, 北澤 理子, 中島 元夫, 前田 盛, 北澤 荘平 日本骨代謝学会雑誌 19 (2) 89 -89 2001年07月 [無し][無し]
  • 副甲状腺腺腫の細胞増殖能は疾患重症度を規定する Ca感知受容体(CaSR)及びビタミンD受容体(VDR)発現の低下との関連
    矢野 彰三, 杉本 利嗣, 塚本 達雄, 山口 徹, 千原 和夫, 小林 彰, 北澤 荘平, 前田 盛, 北澤 理子 日本骨代謝学会雑誌 19 (2) 108 -108 2001年07月 [無し][無し]
  • 1,25(OH)2 Vitamin D3によるマウス破骨細胞抑制因子(OPG)発現調節機構の解析
    近藤 武史, 北澤 理子, 前田 盛, 北澤 荘平 日本骨代謝学会雑誌 19 (2) 9 -9 2001年07月 [無し][無し]
  • ヒト破骨細胞分化因子(RANKL/ODF)遺伝子の5'側上流領域の解析
    梶本 和義, 北澤 理子, 前田 盛, 北澤 荘平 日本骨代謝学会雑誌 19 (2) 8 -8 2001年07月 [無し][無し]
  • 近藤 武史, 北澤 理子, 前田 盛, 北澤 荘平 日本臨床細胞学会雑誌 40 (3) 300 -301 2001年05月 [無し][無し]
     
    症例は68歳男.下肺野に異常陰影が出現し,気管支擦過細胞診で腺癌と診断された.右下葉部分切除術及び横隔膜面播種巣の摘出術を施行した.手術所見はT4NXM0P2D1であった.腎癌の既往のある症例に発生した肉腫様形態を示す肺癌であったため,腎癌の肺転移との鑑別を要したが,既往の腎癌はStage Iであり,組織学的にも肺腫瘍は粘液産生性腺癌であるのに対し,腎腫瘍は乳頭状腎細胞癌であることから腎癌肺転移は否定的であった
  • 副甲状腺腺腫におけるCa感知受容体(CaSR)及びビタミンD受容体(VDR)発現の低下は細胞増殖能と疾患重症度に関与する
    矢野 彰三, 杉本 利嗣, 塚本 達雄, 山口 徹, 小林 彰, 北澤 荘平, 前田 盛, 北澤 理子, 千原 和夫 日本内分泌学会雑誌 77 (1) 97 -97 2001年04月 [無し][無し]
  • 高齢発症のmesodiverticular band(MB)による紋扼性イレウスの1剖検例
    さか本 喜雄, 北澤 理子, 近藤 武史, 前田 盛, 北澤 荘平 診断病理 18 (2) 144 -146 2001年04月 [無し][無し]
     
    86歳男.主訴は便秘,嘔吐で81歳頃より徐々に発語・嚥下等が困難となり仮性球麻痺と診断された.摂食不能の為,胃瘻造設術が施行され,以後在宅にてfollow upされ経過順調であったが,便秘・嘔吐が出現し,腹部X線で鏡面像を認めた為イレウスと診断された.病理組織所見で絞扼を惹起した索状物の中に,動脈が確認され,動脈の管腔内には血液成分を認めた.静脈と神経組織は認めなかった.組織学的にMesodivertiular bandと診断した
  • 血球貪食症候群として発症したEBV関連T細胞性リンパ腫の1例
    藤本 昌代, 北澤 荘平, 近藤 武史, 井上 広之, 梶本 和義, 前田 盛, 北澤 理子 診断病理 18 (2) 200 -202 2001年04月 [無し][無し]
     
    14歳男.主訴は発熱,倦怠感,嘔吐.若年性関節リウマチの診断で,6年前よりprednisolone少量内服を続けていた.1週間前より発熱・倦怠感を生じ,精査にて汎血球減少を指摘され入院.骨髄穿刺にて組織球増加,少数の血球貪食像を認めたが異型細胞は見られず,遺伝子異常やTCR Cβ1歳構成は認められなかった.発熱,汎血球減少,LDH・フェリチン・GOT・GPT・TGの上昇,フィブリノーゲン・T-cholの減少からHPSが疑われ,HLH-94 protocolに従いcyclosporin A,dexamethasone,G-CSF投与を開始するが病状は増悪し,入院2週間後,腹腔内出血・急性肺水腫の為に死亡した.病理解剖にてUCHL-1陽性異型リンパ球の増殖とEBウィルスのmonoclonalな組み込みが証明されEBV関連T細胞性リンパ腫と診断した
  • ヒトAPC遺伝子5'側上流領域のCpG islandメチル化の状態と遺伝子発現との関係
    さか本 喜雄, 北澤 理子, 前田 盛, 北澤 荘平 日本病理学会会誌 90 (1) 180 -180 2001年03月 [無し][無し]
  • Microdissection法を用いたE-Cadherin遺伝子CpGメチル化の検索
    Darwanto Agus, 北澤 理子, さか本 喜雄, 前田 盛, 北澤 荘平 日本病理学会会誌 90 (1) 235 -235 2001年03月 [無し][無し]
  • 1,25(OH)2 Vitamin D3によるマウス破骨細胞抑制因子(OPG/OCIF)発現調節機構の解析
    近藤 武史, 北澤 理子, 前田 盛, 北澤 荘平 日本病理学会会誌 90 (1) 154 -154 2001年03月 [無し][無し]
  • 副甲状腺ホルモン関連蛋白による破骨細胞分化因子(RANKL/ODF)遺伝子発現調節機構
    北澤 荘平, 北澤 理子, 前田 盛 日本病理学会会誌 90 (1) 175 -175 2001年03月 [無し][無し]
  • 乳癌骨浸潤過程における破骨細胞分化因子(RANKL/ODF)の関与
    北澤 理子, 北澤 荘平, 前田 盛 日本病理学会会誌 90 (1) 181 -181 2001年03月 [無し][無し]
  • 肺癌溶骨性骨転移巣における血管新生とVEGFの発現
    西條 雅康, 北澤 荘平, 南 利江子, 前田 盛, 北澤 理子 日本病理学会会誌 90 (1) 191 -191 2001年03月 [無し][無し]
  • ヒト肺癌細胞株におけるTGF-βによるPTHrP遺伝子発現の変化についての検討
    金 永学, 北澤 理子, 前田 盛, 北澤 荘平 日本病理学会会誌 90 (1) 161 -161 2001年03月 [無し][無し]
  • ヒト破骨細胞分化因子(RANKL/ODF)遺伝子の5'側上流領域の解析
    梶本 和義, 北澤 理子, 前田 盛, 北澤 荘平 日本病理学会会誌 90 (1) 163 -163 2001年03月 [無し][無し]
  • 血球貪食症候群として発症したEBV関連LGL白血病の1例
    藤本 昌代, 北澤 荘平, 北澤 理子, 井上 広之, 近藤 武史, 前田 盛 日本病理学会会誌 90 (1) 269 -269 2001年03月 [無し][無し]
  • 正常リンパ組織および悪性リンパ腫におけるTCL1発現
    井上 広之, 北澤 荘平, 北澤 理子, 村尾 眞一, 前田 盛 日本病理学会会誌 90 (1) 267 -267 2001年03月 [無し][無し]
  • 前立腺癌の増殖・進展におけるendothelin receptor-Aの発現の意義
    郷司 和男, 佐々木 幸生, 北澤 荘平, 玉田 博, 三宅 秀明, 勝岡 洋治, 中島 元夫 日本泌尿器科学会雑誌 92 (2) 268 -268 2001年02月 [無し][無し]
  • 泌尿器科癌の浸潤・転移研究の新しい流れ 臨床への応用 膀胱癌におけるHeparanase発現の臨床的意義
    郷司 和男, 岡本 雅之, 北澤 荘平, 平野 博嗣, 豊島 美菜子, 董 堅, 勝岡 洋治, 中島 元夫 日本泌尿器科学会雑誌 92 (2) 107 -108 2001年02月 [無し][無し]
  • Pseude-Meigs症候群を合併した卵巣類内膜癌症例
    武内 享介, 舟木 馨, 藤田 一郎, 早川 陽子, 仁木 敏晴, 北沢 荘平, 北沢 理子 産婦人科治療 82 (1) 114 -117 2001年01月 [無し][無し]
     
    症例は51歳の女性で,呼吸困難と食欲不振を初発症状として内科を受診し右胸水貯留として入院精査を受けた患者である.卵巣癌の末期を想定して開腹手術を行い,右卵巣類内膜癌であること病理組織学的検討により明らかとなった.細胞診で胸水中や腹水中に悪性細胞は証明されず,術中にも播種は認められなかった.術後翌日13日目には胸水は殆ど消失し,化学療法を行ったが8ヵ月後も胸水の再貯留や癌の再発を認めない.胸腹水を示す女性の診療ではMeigs症候群又はPseude-Meigs症候群である可能性を考え,手術不能例と即断しない態度が肝要である
  • In situ hybridizationの総括と展望 再生研究と硬組織のin situ hybridization 骨折治癒における組織改変を担う遺伝子の解析
    北澤 理子, 北澤 荘平, 前田 盛 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 41回 38 -38 2000年12月 [無し][無し]
  • 乳癌骨浸潤過程における副甲状腺ホルモン関連蛋白と破骨細胞分化因子の発現
    北澤 荘平, 北澤 理子 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 41回 92 -92 2000年12月 [無し][無し]
  • 劉 嘉忠, 谷 聡, 萩原 良輔, 加地 正明, 前田 みちる, 八木 規夫, 森田 宗孝, 山下 順平, 新海 政幸, 池川 隆一郎, 今西 築, 平田 勇三, 北澤 荘平 日本消化器病学会雑誌 97 (11) 1401 -1403 2000年11月 [無し][無し]
  • 分子生物学的解析からみた泌尿器科癌の進展機序 ヘパラナーゼ:癌の浸潤・転移における役割
    郷司 和男, 勝岡 洋治, 岡本 雅之, 守殿 貞夫, 北澤 荘平, 豊島 美菜子, 董 堅, 中島 元夫 泌尿器科紀要 46 (10) 757 -762 2000年10月 [無し][無し]
  • Transcriptional regulation mechanism of mouse osteoclast differentiation factor (RANKL/ODF) gene.
    R Kitazawa, S Kitazawa JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 15 S277 -S277 2000年09月 [無し][無し]
  • Characterization of 5 '-flanking region of mouse osteoprotegerin (OPG/OCIF) gene.
    T Kondo, R Kitazawa, H Mori, S Maeda, S Kitazawa JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 15 S277 -S277 2000年09月 [無し][無し]
  • Fra-2 and Jun-D heterodimer mediates PTHrP signaling for RANKL/ODF gene.
    S Kitazawa, R Kitazawa JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 15 S269 -S269 2000年09月 [無し][無し]
  • Association of decreased calcium-sensing receptor expression with proliferation of parathyroid glands in secondary hyperparathyroidism.
    S Yano, T Sugimoto, T Yamaguchi, K Chihara, A Kobayashi, S Kitazawa, S Maeda, R Kitazawa JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 15 S448 -S448 2000年09月 [無し][無し]
  • Expression of RANKL and Cbfa-1 during fracture healing.
    H Mori, R Kitazawa, T Fujimoto, K Mizuno, S Maeda, S Kitazawa JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 15 S245 -S245 2000年09月 [無し][無し]
  • 金永学, 北沢理子, 前田盛, 北沢荘平 Jpn J Cancer Res 91 (Supplement (Sept)) 486 2000年09月 [無し][無し]
  • ヒト大腸癌細胞株におけるAPC遺伝子5'側上流領域のCpG lociメチル化の状態と遺伝子発現との関係
    さか本 喜雄, 北澤 理子, 青山 伸郎, 前田 盛, 北澤 荘平 日本癌学会総会記事 59回 310 -310 2000年09月 [無し][無し]
  • インドネシアと日本における大腸・直腸癌の組織型分布の違いに関する臨床病理学的研究
    前田 盛, Darwanto Agus, Martoprawiro Soegeng S, 北澤 荘平 日本癌学会総会記事 59回 373 -373 2000年09月 [無し][無し]
  • 副甲状腺ホルモン関連蛋白(PTHrP)による破骨細胞分化因子(RANKL/ODF)遺伝子発現調節機構
    北澤 荘平, 北澤 理子, 前田 盛 日本癌学会総会記事 59回 456 -457 2000年09月 [無し][無し]
  • 肺癌細胞株におけるPTHrP遺伝子CpGアイランドのメチル化とTGF-βによるpromoter usageの変化についての検討
    金 永学, 北澤 理子, 前田 盛, 北澤 荘平 日本癌学会総会記事 59回 486 -486 2000年09月 [無し][無し]
  • 片側下眼瞼にみられた限局性アミロイドーシスの1例
    下川 綾, 木村 良平, 中村 貞彦, 千葉 剛, 近藤 武史, 北澤 荘平 眼科臨床医報 94 (7) 967 -967 2000年07月 [無し][無し]
  • 骨折治癒過程における破骨細胞分化因子(RANKL/ODF)とCbfa-1の発現局在
    森 裕之, 北澤 理子, 藤本 卓也, 前田 盛, 水野 耕作, 北澤 荘平 日本骨代謝学会雑誌 18 (2) 26 -26 2000年06月 [無し][無し]
  • Parathyroid Hormone-related Proteinによる破骨細胞分化因子(RANKL/ODF)遺伝子発現調節機構の解析
    北澤 荘平, 北澤 理子 日本骨代謝学会雑誌 18 (2) 96 -96 2000年06月 [無し][無し]
  • 腎不全による二次性副甲状腺機能亢進症の進展におけるカルシウム感知受容体の役割 細胞増殖能との関係
    矢野 彰三, 杉本 利嗣, 塚本 達雄, 千原 和夫, 小林 彰, 北澤 荘平, 前田 盛, 北澤 理子 日本骨代謝学会雑誌 18 (2) 132 -132 2000年06月 [無し][無し]
  • マウス破骨細胞抑制因子(OPG/OCIF)遺伝子5'側上流領域の解析
    近藤 武史, 北澤 理子, 森 裕之, 前田 盛, 北澤 荘平 日本骨代謝学会雑誌 18 (2) 130 -130 2000年06月 [無し][無し]
  • 乳癌骨浸潤過程における破骨細胞分化因子(RANKL/ODF)遺伝子発現の解析
    北澤 理子, 森 裕之, 前田 盛, 北澤 荘平 日本骨代謝学会雑誌 18 (2) 159 -159 2000年06月 [無し][無し]
  • 二次性副甲状腺機能亢進症例の副甲状腺におけるCa感知受容体及びビタミンD受容体発現の細胞増殖能への関与
    矢野 彰三, 杉本 利嗣, 塚本 達雄, 千原 和夫, 小林 彰, 北澤 荘平, 前田 盛, 北澤 理子 日本透析医学会雑誌 33 (Suppl.1) 632 -632 2000年05月 [無し][無し]
  • 【乳癌の診断と治療】 進行・再発乳癌の治療 新しい機序の薬物療法 Bisphosphonate
    河野 範男, 北澤 荘平 日本臨床 58 (増刊 乳癌の診断と治療) 345 -351 2000年04月 [無し][無し]
  • 高度二次性副甲状腺機能亢進症をきたした腎不全患者の副甲状腺におけるカルシウム感知受容体及びビタミンD受容体の発現と細胞増殖能との関係
    矢野 彰三, 杉本 利嗣, 千原 和夫, 小林 彰, 北澤 荘平, 前田 盛, 北澤 理子 日本内分泌学会雑誌 76 (1) 207 -207 2000年04月 [無し][無し]
  • 【In situ hybridization】 mRNA in situ hybridizationの基本的技法 非放射性プローブ
    北澤 荘平, 北澤 理子, 前田 盛 病理と臨床 18 (臨増) 245 -251 2000年03月 [無し][無し]
  • ヒトAPC遺伝子とhMLH1遺伝子5'側上流領域のCpG locusメチル化と遺伝子発現との関係
    さか本 喜雄, 北澤 理子, Agus Darwanto, 青山 伸郎, 前田 盛, 北澤 荘平 日本病理学会会誌 89 (1) 217 -217 2000年03月 [無し][無し]
  • II型コラーゲン関節炎モデルマウスにおける破骨細胞分化因子(ODF),RANK,破骨細胞抑制因子(OPG)mRNAの発現
    森 裕之, 北澤 理子, 藤本 卓也, 水木 伸一, 能勢 眞人, 水野 耕作, 前田 盛, 北澤 荘平 日本病理学会会誌 89 (1) 208 -208 2000年03月 [無し][無し]
  • 高Ca血症にPTH関連蛋白(PTHrP)が関与したと思われる多発性骨髄腫の1例
    梶本 和義, 北澤 理子, 森 裕之, 宗和 秀明, 杉本 利嗣, 松井 利光, 山口 徹, 千原 和夫, 北澤 荘平, 前田 盛 日本病理学会会誌 89 (1) 260 -260 2000年03月 [無し][無し]
  • 多臓器に高度の線維化及び髄外造血を認めた原発性骨髄線維症の1剖検例
    金 永学, 北澤 荘平, 北澤 理子, さか本 喜雄, 上野 博久, 尹 聖哲, 春日 雅人, 近藤 武史, 前田 盛 日本病理学会会誌 89 (1) 255 -255 2000年03月 [無し][無し]
  • ヒト胆嚢癌におけるS100A4とE-Cadherin発現の検討
    中村 哲, 村尾 眞一, 片山 直弥, 味木 徹夫, 北澤 荘平, 北澤 理子, 黒田 嘉和, 前田 盛 日本病理学会会誌 89 (1) 291 -291 2000年03月 [無し][無し]
  • マウス破骨細胞抑制因子(OPG/OCIF)遺伝子5'側上流領域の解析
    近藤 武史, 北澤 理子, 前田 盛, 北澤 荘平 日本病理学会会誌 89 (1) 177 -177 2000年03月 [無し][無し]
  • マウス破骨細胞分化因子(RANKL/ODF)遺伝子発現調節機構の解析 VitDとCbfa-1の関与
    北澤 理子, 北澤 荘平, 前田 盛 日本病理学会会誌 89 (1) 174 -174 2000年03月 [無し][無し]
  • 転写因子と疾患 病理組織標本を用いた遺伝子5'側上流領域CpG locusメチル化の検討
    北澤 荘平, 北澤 理子, 前田 盛 日本病理学会会誌 89 (1) 137 -137 2000年03月 [無し][無し]
  • 膀胱癌の浸潤・転移及び血管新生におけるHeparanaseの意義
    岡本 雅之, 北澤 荘平, 守殿 貞夫, 勝岡 洋治, 中島 元夫 日本泌尿器科学会雑誌 91 (3) 251 -251 2000年03月 [無し][無し]
  • B細胞性リンパ腫におけるTCL1とBCL2発現の関連
    井上 広之, 村尾 眞一, 中村 哲, 北澤 荘平, 北澤 理子, 前田 盛 日本病理学会会誌 89 (1) 240 -240 2000年03月 [無し][無し]
  • A型胃炎に伴った多発性胃カルチノイドの1例
    谷 聡, 前田 みちる, 萩原 良輔, 劉 嘉忠, 加地 正明, 八木 規夫, 森田 宗孝, 松岡 彰, 山下 順平, 新海 政幸, 今西 築, 犬島 浩一, 北澤 荘平 兵庫県医師会医学雑誌 42 (3) 172 -176 2000年03月 [無し][無し]
     
    61歳,男.胃内視鏡検査にて穹窿部から体部大彎にかけて多数の隆起性病変を認めたため1999年4月に入院.超音波内視鏡では隆起性病変はいずれも粘膜下層に存在し内部は均一な低エコー像を呈し,生検にてカルチノイド腫瘍と診断された.血清ガストリンは著明に上昇し,セトロニン及び5-HIAAも軽度上昇,抗胃壁細胞抗体が陽性であった.遠隔転移を認めず胃全摘術リンパ節郭清D1を施行し,(stage I:PoHoNoTo),病理組織では浸達度sm,ly1,v0,n(-)で,胃体部に萎縮性胃炎を伴っていた.胃の多発性カルチノイドの報告は少なく,本症例は高ガストリン血症とA型慢性胃炎を背景に発症した症例である
  • 小腸に原発した扁平上皮癌の1例
    寒原 芳浩, 石川 羊男, 中谷 正史, 西村 隆一, 木崎 智彦, 北澤 理子, 北澤 荘平 癌の臨床 46 (2) 158 -162 2000年02月 [無し][無し]
     
    41歳女,背部痛を主訴として来院した.腹部エコー,CTにて鞍状腫瘍を認め,小腸造影では腫瘍内に造影剤を認め,血管造影にて中結腸動脈左枝に3cmにわたる血管不整狭窄像を認めた.横行結腸間膜へ浸潤した小腸癌を疑い開腹術を施行した.手術時,空腸に7cm大の腫瘤を認め,横行結腸間膜膵体部下部及び脾静脈に浸潤していた.上部小腸切除,横行結腸部分切除,膵体尾部脾合併切除を行った.病理組織学的検索では,腫瘍は全て扁平上皮癌成分よりなり,SCC,PTHrP陽性であった.手術後5年を経過して再発の徴候はなく経過している
  • 矢野 彰三, 杉本 利嗣, 神澤 道子, 北澤 理子, 北澤 荘平, 前田 盛, 小林 彰, 千原 和夫 日本透析医学会雑誌 33 (1) 53 -59 2000年01月 [無し][無し]
     
    34歳男.慢性糸球体腎炎による腎不全のため平成3年より維持血液透析中であったが,極めて重度の二次性副甲状腺機能亢進症のため当院紹介となった.血中補正Ca 10.9mg/dl,intact PTH 3500pg/ml,ALP 13729 IU/L,osteocalcin 3140ng/ml,TRAP 44.0 IU/Lと血中PTH及び骨代謝回転の異常高値を呈した.ビタミンD経口パルス療法が無効であったため,平成9年5月parathyroidectomy(PTx)を施行したところ,骨痛,貧血,Xp所見及び骨代謝マーカー等検査値の著明な改善が認められた.切除された副甲状腺は4腺で合計2.5g,一部結節形成を伴う瀰漫性増殖を示していた.免疫組織化学的には結節内にはKi67陽性細胞が多数認められ,又,瀰漫性増殖を示す腺でも増殖能の高い部位でのビタミンD受容体,カルシウム感知受容体発現は増殖能の低い部位に比し著明に低下していた
  • 大腸内視鏡検査が誘因と思われた虚血性大腸炎の2例
    岸本 美也子, 北垣 一成, 楯谷 三四郎, 濱田 康弘, 本迫 洋一郎, 安藤 章文, 滝 俊哉, 中田 吉彦, 北澤 荘平 甲南病院医学雑誌 19 9 -13 1999年12月 [無し][無し]
     
    症例1:64歳男.61歳時より高血圧,62歳時大腸ポリペクトミーの既往がある.大腸内視鏡検査を受け特に異常所見はみられなかったが,検査中,徐脈,血圧低下を認め,フルマゼニル投与と点滴にて軽快した.同日夜少量の下血を認め,翌日には腹痛も出現したため,内視鏡検査施行,S状結腸から脾曲部迄の虚血性大腸炎を認めた.症例2:61歳女.33歳時左卵巣嚢腫手術の既往があり,時に狭心症様症状を認めていた.平成11年5月13日大腸内視鏡検査を受け上行結腸の憩室を指摘された.同日夕方より下血,腹部不快感が出現し,翌日の内視鏡検査で横行結腸を主病変とする虚血性大腸炎を認めた
  • 出射 由香, 釜田 里江, 南 香織, 平手 ゆかり, 北澤 荘平, 前田 盛 日本臨床細胞学会雑誌 38 (6) 570 -573 1999年11月 [無し][無し]
  • 【ビスホスホネートの癌への新展開】 乳癌の骨転移治療とビスホスホネート
    河野 範男, 北沢 荘平, 川口 勝徳 Clinical Calcium 9 (11) 1420 -1426 1999年10月 [無し][無し]
  • Bone morphogenetic protein (BMP)-3 mRNA expression in endochondral ossification.
    T Fujimoto, R Kitazawa, H Mori, K Mizuno, S Maeda, S Kitazawa JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 14 S309 -S309 1999年09月 [無し][無し]
  • Methylation status of CpG island of adenomatous polyposis coli (APC) gene and its relationship to gene expression in colon cancer cell lines
    Y Sakamoto, R Kitazawa, N Aoyama, S Maeda, S Kitazawa EUROPEAN JOURNAL OF CANCER 研究発表ペーパー・要旨(国際会議) 35 S190 -S190 1999年09月 [無し][無し]
  • Osteoclast differentiation factor (ODF/OPGL/RANKL/TRANCE) expression in bone invasion model of breast cancer.
    S Kitazawa, H Mori, S Maeda, R Kitazawa JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 14 S153 -S153 1999年09月 [無し][無し]
  • Molecular cloning and characterization of mouse osteoclast differentiation factor (TRANCE/RANKL/OPGL/ODF) gene promoter.
    R Kitazawa, S Maeda, S Kitazawa JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 14 S197 -S197 1999年09月 [無し][無し]
  • Expression of ODF/OPGL, RANK and OPG mRNA in collagen-induced arthritis in mice.
    H Mori, R Kitazawa, T Fujimoto, K Mizuno, S Maeda, S Kitazawa JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 14 S176 -S176 1999年09月 [無し][無し]
  • ヒト前立腺癌におけるBMP-6遺伝子5'側上流領域CpG lociメチル化の解析
    玉田 博, 北澤 理子, 郷司 和男, 守殿 貞夫, 前田 盛, 北澤 荘平 日本癌学会総会記事 58回 117 -117 1999年08月 [無し][無し]
  • ヒト胆嚢癌におけるS100A4とE-Cadherin発現の検討
    中村 哲, 村尾 眞一, 片山 直弥, 味木 徹夫, 北澤 荘平, 北澤 理子, 黒田 嘉和, 前田 盛 日本癌学会総会記事 58回 401 -401 1999年08月 [無し][無し]
  • 乳癌骨転移・浸潤モデルにおける破骨細胞分化因子の発現局在
    北澤 荘平, 北澤 理子, 玉田 博, 森 裕之, 近藤 武史, 前田 盛 日本癌学会総会記事 58回 252 -252 1999年08月 [無し][無し]
  • II型コラーゲン関節炎モデルマウスにおける破骨細胞分化因子(ODF),RANK,破骨細胞抑制因子(OPG)mRNAの発現
    森 裕之, 北澤 理子, 藤本 卓也, 水木 伸一, 能勢 眞人, 前田 盛, 水野 耕作, 北澤 荘平 日本整形外科学会雑誌 73 (8) S1878 -S1878 1999年08月 [無し][無し]
  • 内軟骨性骨化におけるBMP-3の発現
    藤本 卓也, 北澤 理子, 森 裕之, 前田 盛, 水野 耕作, 北澤 荘平 日本整形外科学会雑誌 73 (8) S1768 -S1768 1999年08月 [無し][無し]
  • ヒトAPC遺伝子5'側上流領域のCpG islandメチル化の状態と遺伝子発現との関係
    さか本 喜雄, 北澤 理子, 青山 伸郎, 前田 盛, 北澤 荘平 日本癌学会総会記事 58回 530 -530 1999年08月 [無し][無し]
  • ヒト胆嚢癌細胞の浸潤能を制御するS100A4(calvasculin,mst-1)遺伝子発現
    片山 直弥, 村尾 真一, 中村 哲, 味木 徹夫, 北澤 荘平, 北澤 理子, 黒田 嘉和, 前田 盛 日本癌学会総会記事 58回 624 -624 1999年08月 [無し][無し]
  • 血中PTH及び骨代謝回転の異常高値を示した二次性副甲状腺機能亢進症の一例 Ca感知受容体の関与
    矢野 彰三, 杉本 利嗣, 神澤 道子, 中岡 大樹, 千原 和夫, 北澤 理子, 北澤 荘平, 前田 盛, 小林 彰 日本透析医学会雑誌 32 (Suppl.1) 612 -612 1999年06月 [無し][無し]
  • II型コラーゲン関節炎モデルマウスにおける破骨細胞分化因子(ODF),RANK,破骨細胞抑制因子(OPG)mRNAの発現
    森 裕之, 北澤 理子, 藤本 卓也, 水木 伸一, 能勢 眞人, 前田 盛, 水野 耕作, 北澤 荘平 日本骨代謝学会雑誌 17 (2) 129 -129 1999年06月 [無し][無し]
  • 内軟骨性骨化におけるBMP-3の発現
    藤本 卓也, 北澤 理子, 森 裕之, 前田 盛, 水野 耕作, 北澤 荘平 日本骨代謝学会雑誌 17 (2) 208 -208 1999年06月 [無し][無し]
  • マウス破骨細胞分化因子(TRANCE/RANKL/ODF/OPGL)遺伝子発現調節機序の解析
    北澤 理子, 北澤 荘平, 前田 盛 日本骨代謝学会雑誌 17 (2) 118 -118 1999年06月 [無し][無し]
  • 骨折治癒過程における破骨細胞分化因子(ODF)mRNAの発現
    森 裕之, 北澤 理子, 藤本 卓也, 前田 盛, 水野 耕作, 北澤 荘平 日本骨代謝学会雑誌 17 (2) 122 -122 1999年06月 [無し][無し]
  • 谷 聡, 古川 健亮, 福田 昌輝, 前田 みちる, 坂井 誠, 森田 宗孝, 山下 順平, 北澤 荘平, 老籾 宗忠 日本消化器病学会雑誌 96 (5) 540 -544 1999年05月 [無し][無し]
     
    27歳女.アセトアミノフェンを含む薬剤を自殺目的に大量服用し昏睡状態で入院した.直ちに血液浄化を施行し,併発した肺水腫に対しては人工呼吸管理下に治療し第10病日に意識が回復した.経過中,PLA2等の膵酵素が著明に上昇,腹痛はなかったがCTで膵の浮腫を認めナファスモスタット投与にて改善した
  • 血中PTH及び骨代謝回転の異常高値を示した二次性副甲状腺機能亢進症の1例:Ca感知受容体の関与
    矢野 彰三, 杉本 利嗣, 神澤 道子, 千原 和夫, 北澤 理子, 北澤 荘平, 前田 盛, 小林 彰 Clinical Calcium 9 (6) 782 -785 1999年05月 [無し][無し]
  • Methylation status of CpG island of adenomatous polyposis coli (APC) gene and its relationship to gene expression in colon cancer cell lines
    Y Sakamoto, R Kitazawa, N Aoyama, S Maeda, S Kitazawa GASTROENTEROLOGY 研究発表ペーパー・要旨(国際会議) 116 (4) A495 -A495 1999年04月 [無し][無し]
  • ビスホスフォネート療法の現状と近未来 癌骨転移予防はビスホスフォネートにより可能か とくに乳癌に関して
    河野 範男, 北澤 荘平 医学のあゆみ 189 (2) 127 -127 1999年04月 [無し][無し]
  • DMBAラット白血病の特異的N-ras異常の誘発に及ぼす増殖因子の影響
    杉山 武敏, 逢坂 光彦, 小網 健市, 北沢 荘平, 前田 盛 日本病理学会会誌 88 (1) 313 -313 1999年03月 [無し][無し]
  • 谷 聡, 古川 健亮, 福田 昌輝, 西澤 昭彦, 坂井 誠, 森田 宗孝, 山下 順平, 北澤 荘平, 老籾 宗忠 Gastroenterological Endoscopy 41 (3) 340 -344 1999年03月 [無し][無し]
     
    50歳女.大腸内視鏡で横行結腸に径8mmの粘膜下腫瘍(カルチノイド)を認め,粘膜切除術(EMR)を施行し切断面をクリップにて縫縮した.術後,心窩部痛と発熱が出現,腹部CTでfree airを認め穿孔性腹膜炎と診断したが,腹膜刺激症状を欠いたため保存的に治療した.その後,炎症所見は改善し10日後に退院した
  • マウス破骨細胞形成因子(RANKL/TRANCE/OPGL/ODF)遺伝子5'側上流領域の解析
    北澤 理子, 北澤 荘平, 前田 盛 日本病理学会会誌 88 (1) 116 -116 1999年03月 [無し][無し]
  • 病理診断における遺伝子診断と新技術の応用 ホルマリン固定パラフィン包埋材料を用いたメチル化シトシン検出法に関する基礎的検討
    北澤 荘平, 北澤 理子, 前田 盛 日本病理学会会誌 88 (1) 130 -130 1999年03月 [無し][無し]
  • S100蛋白種の正常心筋及び心筋障害モデルでの局在と発現の検討
    稲本 真也, 村尾 眞一, 北澤 荘平, 横山 光宏, 前田 盛 日本病理学会会誌 88 (1) 292 -292 1999年03月 [無し][無し]
  • 骨折治癒過程における破骨細胞分化因子(ODF)mRNAの発現
    森 裕之, 北澤 理子, 藤本 卓也, 水野 耕作, 北澤 荘平 日本病理学会会誌 88 (1) 282 -282 1999年03月 [無し][無し]
  • 骨折治癒過程におけるBMP-2,BMP-3 mRNAの発現
    藤本 卓也, 北澤 理子, 森 裕之, 水野 耕作, 前田 盛, 北澤 荘平 日本病理学会会誌 88 (1) 282 -282 1999年03月 [無し][無し]
  • ヒト前立腺組織におけるBMP-6遺伝子5側上流領域CpG lociメチル化の解析
    玉田 博, 北澤 理子, 守殿 貞夫, 前田 盛, 北澤 荘平 日本病理学会会誌 88 (1) 208 -208 1999年03月 [無し][無し]
  • ヒトAPC遺伝子5'側上流領域のCpG islandメチル化と遺伝子発現との関係
    さか本 喜雄, 北澤 理子, 青山 伸郎, 前田 盛, 北澤 荘平 日本病理学会会誌 88 (1) 307 -307 1999年03月 [無し][無し]
  • ヒト胆道系癌細胞の浸潤能とS100A4(calvasculin,mst-1)の発現
    片山 直弥, 村尾 眞一, 中村 哲, 北澤 荘平, 北澤 理子, 前田 盛 日本病理学会会誌 88 (1) 317 -317 1999年03月 [無し][無し]
  • 胆嚢癌細胞におけるS100A4蛋白発現とTet-Off TMGene Expression Systemを用いた発現調節の検討
    中村 哲, 村尾 眞一, 北澤 荘平, 北澤 理子, 前田 盛 日本病理学会会誌 88 (1) 262 -262 1999年03月 [無し][無し]
  • 古川 健亮, 谷 聡, 福田 昌輝, 西澤 昭彦, 坂井 誠, 森田 宗孝, 今西 築, 山下 順平, 北澤 荘平, 老籾 宗忠 日本消化器病学会雑誌 96 (2) 160 -163 1999年02月 [無し][無し]
  • 骨折治癒過程におけるBMP-3 mRNAの発現
    藤本 卓也, 北澤 理子, 北澤 荘平, 藤井 英紀, 前田 盛, 水野 耕作 骨・関節・靱帯 12 (2) 187 -190 1999年02月 [無し][無し]
  • 谷 聡, 古川 健亮, 福田 昌輝, 西澤 昭彦, 坂井 誠, 森田 宗孝, 北澤 荘平, 老籾 宗忠 日本消化器病学会雑誌 95 (12) 1357 -1361 1998年12月 [無し][無し]
     
    症例1は61歳女性,無症状であったが便潜血反応陽性,症例2は77歳男性で下痢と発熱にて受診した.共に右側結腸は注腸透視でハウストラが消失し内視鏡では粘膜面は血管透見なく粗造で左半結腸には異常を認めず細菌検査は陰性であった.組織検査で右側結腸のみにcrypt abscessを認めサラゾピリン或いはステロイド併用で改善した
  • 胃に発生したgastrointestinal stromal tumor(GIST)の1手術例
    今西 達也, 佐藤 美晴, 塚本 好彦, 黒田 浩光, 北垣 一成, 北澤 荘平 甲南病院医学雑誌 18 30 -32 1998年12月 [無し][無し]
  • 結腸狭窄を認めた結腸子宮内膜症の2手術例
    林 俊, 佐藤 美晴, 塚本 好彦, 黒田 浩光, 今西 達也, 久保田 真毅, 北澤 荘平 甲南病院医学雑誌 18 33 -37 1998年12月 [無し][無し]
     
    症例1は40歳女で,頻回の下痢,下血があり,虚血性大腸炎の診断で約2ヵ月の保存的加療を施行したが,S状結腸の全周性狭窄は改善せず,結腸部分切除術を施行した.症例2は32歳女で,婦人科で子宮筋腫摘出のため開腹手術を行ったところ,子宮がS状結腸に強固に癒着しており,剥離困難で,狭窄所見もあったため,S状結腸を切除した.いずれの症例も術後の病理組織検査で,腸管固有筋層内に子宮内膜組織を認め,結腸の腸管子宮内膜症と診断した
  • 迷入膵を先進部とした腸重積症の1例
    小城 崇弘, 中野 加奈子, 新谷 幸弘, 宮本 元, 山田 至康, 前田 太郎, 相原 浩輝, 三村 恵子, 北澤 荘平 甲南病院医学雑誌 18 41 -43 1998年12月 [無し][無し]
  • 乳腺アポクリン癌の1例
    宮下 勝, 大原 忠敬, 新海 政幸, 山本 武司, 久保田 真毅, 今西 築, 北澤 荘平 甲南病院医学雑誌 18 22 -25 1998年12月 [無し][無し]
  • 出射 由香, 釜田 里江, 南 香織, 平手 ゆかり, 北澤 荘平, 前田 盛 日本臨床細胞学会雑誌 37 (6) 598 -602 1998年11月 [無し][無し]
     
    68歳女.心窩部痛出現,当院外科入院し,各種検査の結果十二指腸乳頭部癌との診断にて手術施行された.術中迅速診断に提出された膵周囲リンパ節からの捺印標本ではN/C比の大きい小型の腫瘍細胞がきめ込み細工状の配列を呈しており,核形は円形ないし類円形で,クロマチンは細顆粒状であり,小細胞癌を疑わせる所見であった.組織学的には胞体に乏しく濃染する核を有するやや小型の腫瘍細胞が充実性に増生しており,硬度のリンパ管侵襲を認めた.免疫組織化学にて腫瘍細胞はNSEに陽性を示し,電顕にて腫瘍細胞の胞体内に内分泌顆粒を認めた.以上の所見より十二指腸乳頭部原発の小細胞癌と診断した
  • 鼠径部脂肪腫の1例
    大岡 均至, 米澤 和之, 北澤 荘平, 岡田 弘 泌尿器科紀要 44 (10) 770 -770 1998年10月 [無し][無し]
  • 腸間膜血腫を生じた上腸間膜動脈瘤破裂の1例
    石田 明彦, 福田 昌輝, 古川 健亮, 西澤 昭彦, 北村 重和, 延沢 彰, 松本 圭司, 坂井 誠, 森田 宗孝, 谷 聰, 岩谷 逸平, 宮崎 宣弘, 小倉 純, 松岡 彰, 山下 順平, 老籾 宗忠, 酒井 瑛, 北澤 荘平 兵庫県医師会医学雑誌 41 (1) 30 -34 1998年09月 [無し][無し]
     
    48歳男,右結腸辺縁動脈瘤破裂による腸間膜血腫を来たした1例を経験し,上腸間膜動脈分枝に発生した動脈瘤について考察を加えた
  • 骨折治癒過程におけるBMP-3mRNAの発現
    藤本 卓也, 北澤 理子, 北澤 荘平, 藤井 英紀, 前田 盛, 水野 耕作 日本整形外科学会雑誌 72 (8) s1357 -s1357 1998年08月 [無し][無し]
  • 骨リモデリングにおけるPDGF β-receptorの関与
    藤井 英紀, 北澤 理子, 北澤 荘平, 藤本 卓也, 前田 盛, 水野 耕作 日本整形外科学会雑誌 72 (8) s1382 -s1382 1998年08月 [無し][無し]
  • サイクリンD1遺伝子5'側上流領域のCpG islandメチル化部位の特定とin vivoにおける脱メチル化の解析
    北澤 荘平, 北澤 理子, 玉田 博, 前田 盛 日本癌学会総会記事 57回 134 -134 1998年08月 [無し][無し]
  • ヒトBMP-6プロモーター領域のCpG islandメチル化による遺伝子発現制御の解析
    玉田 博, 北澤 理子, 郷司 和男, 守殿 貞夫, 前田 盛, 北澤 荘平 日本癌学会総会記事 57回 465 -465 1998年08月 [無し][無し]
  • ヒト大腸癌培養細胞株におけるAPC遺伝子5'側上流領域のCpG islandメチル化による遺伝子発現制御の解析
    さか本 喜雄, 北澤 理子, 青山 伸郎, 前田 盛, 北澤 荘平 日本癌学会総会記事 57回 447 -447 1998年08月 [無し][無し]
  • S100A4遺伝子がヒト扁平上皮癌細胞の浸潤・増殖能に及ぼす影響
    魚住 真樹, 村尾 真一, 中山 伊知郎, 北澤 荘平, 北澤 理子, 前田 盛 日本癌学会総会記事 57回 515 -515 1998年08月 [無し][無し]
  • B細胞性悪性リンパ腫におけるTCL1遺伝子の発現とその機能
    中山 伊知郎, 村尾 真一, 魚住 真樹, 北澤 荘平, 北澤 理子, 前田 盛 日本癌学会総会記事 57回 478 -478 1998年08月 [無し][無し]
  • 【乳癌骨転移の病態と治療】 骨転移の病態関連因子と骨代謝マーカー
    河野 範男, 北澤 荘平, 西原 徳光 乳癌の臨床 13 (2) 253 -259 1998年06月 [無し][無し]
  • ヒトSonic Hedgehog(Shh)遺伝子発現調節機序の検討
    北澤 荘平 日本病理学会会誌 87 (1) 461 -461 1998年03月 [無し][無し]
  • 免疫組織学 in situハイブリダイゼーション(ISH)法
    北澤 荘平 G.I.Research 6 (1) 82 -85 1998年02月 [無し][無し]
  • 骨折治癒過程におけるPDGF及びそのreceptorの発現
    藤井 英紀, 北澤 理子, 北澤 荘平 骨・関節・靱帯 11 (1) 57 -60 1998年01月 [無し][無し]
     
    12週雄BALBマウスの脛骨骨幹部近位1/3に横骨折をおこし,骨折後2〜21日にわたり観察した.PDGF-AA,-BBは2日の血腫;近傍骨膜の未分化間葉系細胞に軽微に発現を認めた.7日以降の内軟骨骨化部の増殖軟骨細胞,肥大化軟骨細胞へと移行する軟骨細胞に発現を認めた.改変期に主に骨芽細胞に認めた.PDGF receptorは血腫内の未分化間葉系細胞にβ-receptor優位のシグナルを認めた.以後骨膜の間葉系細胞,骨芽細胞増殖軟骨細胞にα-,β-receptorを認めた.14日では新生骨の骨芽細胞・破骨細胞にβ-receptorの発現を認めた.PDGFは骨折治癒過程後期のリモデリングにも関与することが示唆された
  • Molecular cloning and characterization of human bone morphogenetic protein (BMP)-3a gene promoter.
    R Kitazawa, S Maeda, S Kitazawa JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 12 F339 -F339 1997年08月 [無し][無し]
  • Expression of platelet-derived growth factor protein and its receptor mRNA during fracture healing in normal mouse
    H Fujii, R Kitazawa, H Kashimoto, S Maeda, K Mizuno, S Kitazawa JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 12 F348 -F348 1997年08月 [無し][無し]
  • Molecular cloning and characterization of human sonic hedgehog (Shh) gene promoter.
    S Kitazawa, R Kitazawa, H Tamada, S Maeda JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 12 F209 -F209 1997年08月 [無し][無し]
  • Molecular cloning and characterization of human bone morphogenetic protein (BMP)-6 gene promotor.
    H Tamada, R Kitazawa, K Goll, S Kamidono, S Maeda, S Kitazawa JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 12 F338 -F338 1997年08月 [無し][無し]
  • インテグリンα6サブユニット遺伝子調節領域の解析
    北澤 荘平 日本癌学会総会記事 56回 375 -375 1997年08月 [無し][無し]
  • 北澤 荘平, 北澤 理子, 前田 盛 電子顕微鏡 32 (2) 100 -102 1997年07月 [無し][無し]
  • 妊娠に合併した腺・扁平上皮内癌の1症例
    武内 享介, 北沢 荘平, 福西 秀信 産婦人科の実際 46 (6) 903 -906 1997年06月 [無し][無し]
  • ラットサイクリンD1遺伝子promoter領域のメチル化,脱メチル化による遺伝子発現調節機構
    北澤 荘平 日本病理学会会誌 86 (1) 169 -169 1997年04月 [無し][無し]
  • 武内 享介, 望月 眞人, 北沢 荘平 日本臨床細胞学会雑誌 36 (2) 244 -248 1997年03月 [無し][無し]
     
    Multilocular peritoneal inclusion cyst(MPIC)は嚢腫様の中皮増殖を主体とする多房性の非上皮性嚢胞である.今回,臨床的にMPICを疑った2症例に対して,経腟超音波下に嚢胞内溶液の穿刺・吸引を行った後,腹腔鏡による嚢胞切除或いは薬物治療を行い再発を防止し得た.2症例とも2回の産婦人科手術の既往があり,いずれも下腹部不快感を主訴として来院した.来院時ダグラス窩に嵌入した無痛性の腫瘤を触れ,画像診断で骨盤壁,腸管に沿って不規則な形で拡がる多房性嚢胞を認めた.既往歴及び画像診断よりMPICを疑い経腟的穿刺吸引細胞診を施行し,きれいな背景の中に孤立散在性の反応性中皮細胞を確認した.これらの症例に対して,腹腔鏡による嚢胞切除と薬物による卵巣機能抑制を行い,切除症例に関しては組織学的にもMPICを確認した.2症例とも術後2〜3年の時点では再発徴候を認めていない
  • 武内 享介, 望月 眞人, 北沢 荘平 臨床婦人科産科 50 (12) 1615 -1618 1996年12月 [無し][無し]
  • Differential display identifies genes related to functional differentiation of mouse bone marrow stromal cells.
    R Kitazawa, S Kitazawa, S Maeda JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 11 M393 -M393 1996年08月 [無し][無し]
  • Molecular cloning and characterization of Long-Evans rat cyclin D1 gene promoter.
    S Kitazawa, R Kitazawa, M Sakaue, K Nishida, H Kashimoto, S Maeda JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 11 M375 -M375 1996年08月 [無し][無し]
  • Fibrinogen promotes osteogenic responses in mesenchymal cells.
    H Kashimoto, R Kitazawa, S Kitazawa, K Nishida, K Mizuno, S Maeda JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 11 S328 -S328 1996年08月 [無し][無し]
  • Molecular cloning and characterization of human bone morphogenic protein (BMP)-5 gene promoter.
    M Sakaue, S Kitazawa, K Nishida, R Kitazawa, S Maeda JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 11 T408 -T408 1996年08月 [無し][無し]
  • Molecular cloning and characterization of human alpha 6 integrin gene promoter.
    K Nishida, S Kitazawa, M Sakaue, R Kitazawa, H Kashimoto, K Mizuno, S Maeda JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 11 T409 -T409 1996年08月 [無し][無し]
  • ラットサイクリンD1遺伝子5'側上流領域の解析
    北沢 荘平 日本病理学会会誌 85 (1) 101 -101 1996年03月 [無し][無し]
  • 「胆嚢ポリープ」のmalignant potential
    味木 徹夫, 藤盛 孝博, 北澤 荘平 消化器外科 19 (2) 213 -218 1996年02月 [無し][無し]
  • 大腸がんの分子生物学 大腸がんの遺伝子診断 特にin situ hybridizationの意義
    阪上 守人, 北澤 荘平, 藤盛 孝博 BIO Clinica 10 (7) 486 -489 1995年07月 [無し][無し]
  • マウス骨髄マクロファージにおけるβ3インテグリンの発現調節
    北沢 荘平 日本病理学会会誌 84 (1) 216 -216 1995年03月 [無し][無し]
  • マンモグラフィの石灰化 乳癌石灰化の主要原因物質および生物学的意義
    河野 範男, 北沢 荘平, 寒原 芳浩 乳癌の臨床 9 (3) 412 -418 1994年09月 [無し][無し]
  • in situ Hybridization法の電顕応用
    北沢 荘平, 北沢 理子, 前田 盛 月刊細胞 25 (12) 470 -474 1993年11月 [無し][無し]
  • 副甲状腺ホルモン関連蛋白(PTHrP)による高カルシウム血症を呈した卵巣癌肺転移の1例
    北沢 理子, 深瀬 正晃, 北沢 荘平 Clinical Calcium 3 (11) 1530 -1532 1993年10月 [無し][無し]
  • EFFECTS OF CYTOKINES ON BETA(3) INTEGRIN EXPRESSION BY MURINE BONE-MARROW MACROPHAGES
    S KITAZAWA, FP ROSS, A SHIOI, SL TEITELBAUM JOURNAL OF BONE AND MINERAL RESEARCH 研究発表ペーパー・要旨(国際会議) 8 S193 -S193 1993年08月 [無し][無し]
  • 癌転移対策・転移巣に対する治療を中心に 乳癌におけるPTHrP発現と骨転移
    河野 範男, 北沢 荘平 Oncologia 26 (1) 7 -12 1993年01月 [無し][無し]
  • SIGNIFICANCE OF DETECTION OF ENTEROVIRUS RNA IN MYOCARDIAL TISSUES BY PCR
    H UENO, Y YOKOTA, H ITOH, S ISHIDO, S KITAZAWA, S MAEDA, Y KATAYAMA, H HOTTA, M HOMMA CIRCULATION 研究発表ペーパー・要旨(国際会議) 86 (4) 6 -6 1992年10月 [無し][無し]
  • 石灰化上皮腫と髄膜腫における副甲状腺ホルモン関連蛋白
    北沢 荘平 日本病理学会会誌 81 (1) 225 -225 1992年04月 [無し][無し]
  • in situ hybridizationの基礎と応用(3) 非放射性プローブを用いたin situ hybridization
    北沢 荘平, 前田 盛 病理と臨床 10 (3) 313 -318 1992年03月 [無し][無し]
  • BudR標識DNAプローブを用いた電顕レベルのin situ hybridization
    姚 重華, 北沢 荘平, 寺本 忠久 医学のあゆみ 159 (2) 123 -124 1991年10月 [無し][無し]
  • 後藤 章暢, 北沢 荘平, 深瀬 正晃 日本泌尿器科学会雑誌 82 (4) 588 -592 1991年04月 [無し][無し]
     
    副甲状腺ホルモン関連蛋白(PTHrP)は,悪性腫瘍に随伴する高カルシウム血症として有名なhumoral hypercalcemia of malignancy (HHM)の主要因子である.抗PTHrPモノクローナル抗体4B3を作製したので,これを用いて腎細胞癌とヒト正常腎組織におけるPTHrPの免疫組織化学的局在を検討した.正常腎組織では遠位尿細管と集合管に陽性所見が得られた.腎細胞癌症例では36例中30例に陽性所見が得られた.腎細胞癌患者では免疫染色反応強度と血清カルシウムレベルとの間に有意の相関はみられなかった.腎細胞癌の組織別では顆粒細胞亜型が淡明細胞亜型に比べより強陽性に反応した.結論として,腎細胞癌におけるPTHrPの存在は稀なことではなく,HHMはPTHrPが生態のホメオスターシスを越えることによって引き起こされる病態と考えられた
  • 乳癌におけるParathyroid Hormone related Protein (PTHrP)の免疫組織学的検討
    北沢 荘平 日本病理学会会誌 80 (1) 154 -154 1991年03月 [無し][無し]
  • 北沢 荘平, 佐藤 清 日本臨床細胞学会雑誌 29 (6) 927 -928 1990年11月 [無し][無し]
  • Bromodeoxyuridine代謝標識プローブを用いたin situ DNA-RNA hybridization法
    西 雅代, 北沢 荘平, 武中 篤 医学のあゆみ 153 (7) 395 -396 1990年05月 [無し][無し]
  • 武中 篤, 北沢 荘平, 小山 隆司 日本泌尿器科学会雑誌 80 (12) 1769 -1775 1989年12月 [無し][無し]
     
    抗デスモゾーム抗体B-11を作製し,その認識抗原の形態学的および生化学的解析を行うとともに,膀胱癌における組織学的分化度との相関を免疫組織学的に検討した.BALB/c nu/nuマウスに移植継代していたヒト食道扁平上皮癌を,BALB/cマウスに免疫しB-11を得た.B-11はIgG 1抗体て,Western blot法で34 kD蛋白を認識し,ABC法,蛍光抗体法および免疫電顕で,正常扁平上皮,移行上皮およびそれらの癌のデスモゾームのみを特異的に認識し,従来報告されている抗デスモゾーム抗体とは異なるものと思われた.ついでこのB-11を用い,47例の膀胱移行上皮癌についてABC法による免疫組織染色を行った.その結果B-11陽性率は,組織学的異型度別では,Grade 1および2がそれぞれ5/6 (83%)および8/11 (73%)と,Grade 3の6/30 (20%)に比べ高く,組織学的浸達度別では,非浸潤癌が13/17 (76%)と浸潤癌の6/20 (20%)に比べ高率で,組織学的浸潤様式別では,INFαが13/19 (68%)とINFβおよびγの4/17 (24%)および2/22 (18%)に比べ高率であった.B-11抗体による免疫組織学的検討は,膀胱移行上皮癌の有用な分化度の指標となり得る
  • Hodgkin Lymphoma (Nodular Sclerosis)におけるc-myc癌遺伝子mRNAの局在 in vivo Bromodeoxyuridine標識DNAを用いたin situ hybridization
    北沢 荘平 医療 43 (増刊) 574 -574 1989年10月 [無し][無し]
  • Humoral Hypercalcemia of Malignancy (HHM)におけるParathyroid hormone related protein (PTHrP)の免疫組織学的検討
    北沢 荘平 日本癌学会総会記事 48回 332 -332 1989年10月 [無し][無し]
  • 胸椎に発生したglomus腫瘍の一例
    北沢 荘平 日本整形外科学会雑誌 63 (6) S749 -S749 1989年06月 [無し][無し]
  • 後縦隔原発悪性傍神経節腫の1剖検例
    北沢 荘平, 前田 盛, 堀尾 光三 癌の臨床 35 (4) 486 -492 1989年03月 [無し][無し]
  • パーソナルコンピュータPC-9800を用いた外科病理診断報告・登録・検索システム dBASE3アプリケーション開発言語(ADL)によるプログラミング
    北沢 荘平, 前田 盛, 杉山 武敏 病理と臨床 7 (3) 381 -385 1989年03月 [無し][無し]
  • in vivo Bromodeoxyuridine標識DNAを用いたin situ hybridization法について
    北沢 荘平 日本臨床細胞学会雑誌 28 (2) 317 -317 1989年03月 [無し][無し]
  • 抗ab 1癌遺伝子産物抗体を用いた白血病細胞株の免疫組織学的検討
    北沢 荘平 日本病理学会会誌 77 180 -180 1988年11月 [無し][無し]
  • 抗デスモゾームモノクローナル抗体の作製とその免疫組織化学的検討(第一報)
    北沢 荘平 日本臨床細胞学会雑誌 27 (5) 721 -721 1988年09月 [無し][無し]
  • 〔早期癌の鑑別診断〕早期癌の染色体異常
    前田 盛, 北沢 荘平, 堀尾 光三 癌の臨床 34 (10) 1264 -1272 1988年08月 [無し][無し]
  • 後縦隔原発悪性傍神経節腫の1剖検例
    北沢 荘平 日本病理学会会誌 76 343 -343 1987年11月 [無し][無し]
  • 杉山 武敏, 前田 盛, 北沢 荘平 臨床検査 31 (11) 1389 -1393 1987年10月 [無し][無し]
  • 合成peptideを抗原とする抗ablモノクローナル抗体の作製とその評価
    北沢 荘平 日本癌学会総会記事 46回 146 -146 1987年08月 [無し][無し]
  • 分娩時に発症した急性ラ氏島炎の1剖検例
    北沢 荘平 日本病理学会会誌 75 495 -495 1986年11月 [無し][無し]
  • Leiomyomatosis peritonealis disseminataの1剖検例
    北沢 荘平 日本病理学会会誌 75 528 -528 1986年11月 [無し][無し]

受賞

  • 2009年 日本組織細胞化学会 論文賞
     JPN
  • 2003年 米国骨代謝学会Young Investigator Award
  • 2002年 日本病理学会学術研究賞
     JPN
  • 2001年 米国骨代謝学会Young Investigator Award
  • 2001年 日本病理学会奨励賞
     JPN
  • 2000年 日本組織細胞化学会 論文賞
     JPN

委員歴

  • 2018年01月 - 現在   Histochemistry and Cell Biology   Editorial Board
  • 2016年04月 - 現在   日本臨床細胞学会   評議員
  • 2015年04月 - 現在   病理と臨床   編集委員
  • 2014年04月 - 現在   日本骨代謝学会   評議員
  • 2010年 - 現在   日本組織細胞化学会   評議員   日本組織細胞化学会
  • 2006年 - 現在   日本病理学会   Pathology International編集員   日本病理学会
  • 1997年 - 現在   日本病理学会   学術評議員   日本病理学会


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