研究者データベース

研究者情報

マスター

アカウント(マスター)

  • 氏名

    岩永 ひろみ(イワナガ ヒロミ), イワナガ ヒロミ

所属(マスター)

  • 医学研究院 生理系部門 解剖学分野

所属(マスター)

  • 医学研究院 生理系部門 解剖学分野

独自項目

syllabus

  • 2020, 基本医学総論, Basic Principles of Medicine, 修士課程, 医学院, 免疫組織化学、in situ hybridization法, 電顕観察 Immunohistochemistry, in situ hybridization, electron microscopy
  • 2020, 基本医学研究, Master's Thesis Research in Medical Sciences, 修士課程, 医学院, 組織切片作製 一般染色と特殊染色 免疫組織化学 in situ hybridization 電顕観察 tissue sectioning hematoxylin-eosin immunohistochemistry in situ hybridization electron microscopy
  • 2020, 基本医学研究法Ⅰ, Basic Research Methods in Medical Sciences, 修士課程, 医学院, 細胞小器官、膜の構造と特性、核の構造と細胞分裂、上皮組織、結合組織、細胞外マトリックス、血球 Organelles, membrane structure and properties, nuclear structure and cell division, epithelial tissue, connective tissue, extracellular matrix, blood cells
  • 2020, 医学総論, Principles of Medicine, 博士後期課程, 医学院, 組織化学、免疫組織化学、電顕観察、in situ hybridization法、レクチン、Caイメージング
  • 2020, 基盤医学研究, Dissertation Research in Medical Sciences, 博士後期課程, 医学院, 組織化学、免疫組織化学、電顕観察、in situ hybridization法、レクチン、Caイメージング
  • 2020, 医学総論, Principles of Medicine, 博士後期課程, 医学研究科, 組織化学、免疫組織化学、電顕観察、in situ hybridization法、レクチン、Caイメージング
  • 2020, 医学研究法Ⅰ, Research Methods in Medical Sciences Ⅰ, 博士後期課程, 医学院, 解剖学、組織学 Anatomy, Histoloty
  • 2020, 組織学実習, Histology Laboratory, 学士課程, 医学部
  • 2020, 解剖学(組織学), Anatomy(Histology), 学士課程, 医学部, 顕微解剖学、組織学、細胞学、形態

timetable

  • 修士課程, 医学院, 2020, 研究発表技法Ⅰ
  • 修士課程, 医学院, 2020, 研究発表技法Ⅱ
  • 博士後期課程, 医学研究科, 2020, 医学研究法Ⅰ
  • 博士後期課程, 医学院, 2020, 研究発表技法Ⅰ
  • 博士後期課程, 医学院, 2020, 研究発表技法Ⅱ

researchmap

プロフィール情報

学位

  • 医学博士(新潟大学)

プロフィール情報

  • 岩永, イワナガ
  • ひろみ, ヒロミ
  • ID各種

    200901090792580324

対象リソース

業績リスト

研究キーワード

  • 知覚神経終末   腎臓間質   中枢神経系シナプス   sensory nerve endings   renal interstitium   Synapses in the central nervous system   

研究分野

  • ライフサイエンス / 解剖学
  • ライフサイエンス / 神経形態学

経歴

  • 1993年 - 1996年 新潟大学 講師
  • 1993年 - 1996年 新潟大学
  • 1987年 - 1993年 新潟大学 助手
  • 1987年 - 1993年 Niigata University, Research Assistant

学歴

  •         - 1987年   新潟大学   医学研究科   解剖学
  •         - 1987年   新潟大学
  •         - 1983年   弘前大学   医学部   医学科
  •         - 1983年   弘前大学

委員歴

  • 1992年   日本リンパ学会   評議員   日本リンパ学会
  • 日本解剖学会   一般会員   日本解剖学会

論文

  • Hiromi Takahashi-Iwanaga, Shunsuke Kimura, Kohtarou Konno, Masahiko Watanabe, Toshihiko Iwanaga
    AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY 313 1 F20 - F29 2017年07月 [査読有り][通常論文]
     
    The natriuretic hormone CCK exhibits its gene transcripts in total kidney extracts. To test the possibility of CCK acting as an intrarenal mediator of sodium excretion, we examined mouse kidneys by 1) an in situ hybridization technique for CCK mRNA in animals fed a normal- or a high-sodium diet; 2) immuno-electron microscopy for the CCK peptide, 3) an in situ hybridization method and immunohistochemistry for the CCK-specific receptor CCKAR; 4) confocal image analysis of receptor-mediated Ca2+ responses in isolated renal tubules; and 5) metabolic cage experiments for the measurement of urinary sodium excretion in high-salt-fed mice either treated or untreated with the CCKAR antagonist lorglumide. Results showed the CCK gene to be expressed intensely in the inner medulla and moderately in the inner stripe of the outer medulla, with the expression in the latter being enhanced by high sodium intake. Immunoreactivity for the CCK peptide was localized to the rough endoplasmic reticulum of the medullary interstitial cells in corresponding renal regions, confirming it to be a secretory protein. Gene transcripts, protein products, and the functional activity for CCKAR were consistently localized to the late proximal tubule segments (S2 and S3) in the medullary rays, and the outer stripe of the outer medulla. Lorglumide significantly diminished natriuretic responses of mice to a dietary sodium load without altering the glomerular filtration rate. These findings suggest that the medullary interstitial cells respond to body fluid expansion by CCK release for feedback regulation of the late proximal tubular reabsorption.
  • Ayuko Kishimoto, Hiromi Takahashi-Iwanaga, Masahiko M. Watanabe, Toshihiko Iwanaga
    EXPERIMENTAL EYE RESEARCH 153 170 - 177 2016年12月 [査読有り][通常論文]
     
    The blood-brain barrier in the neonatal brain expresses the monocarboxylate transporter (MCT)-1 rather than the glucose transporter (GLUT)-1, due to the special energy supply during the suckling period. The hyaloid vascular system, consisting of the vasa hyaloidea propria and tunica vasculosa lentis, is a temporary vasculature present only during the early development of mammalian eyes and later regresses. Although the ocular vasculature manifests such a unique developmental process, no information is available concerning the expression of endothelial nutrient transporters in the developing eye. The present immunohistochemical study using whole mount preparations of murine eyes found that the hyaloid vascular system predominantly expressed GLUT1 in the endothelium, in contrast to the brain endothelium. Characteristically, the endothelium in peripheral regions of the neonatal hyaloid vessels displayed a mosaic pattern of MCT1-immunoreactive cells scattered within the GLUT1-expressing endothelium. The proper retinal vessels first developed by sprouting angiogenesis endowed with filopodia, which were absolutely free from the immunoreactivities of GLUT1 and MCT1. The remodeling retinal capillary networks and veins in the surface layer of the retina mainly expressed MCT1 until the weaning period. Immunostaining of MCT1 in the retina revealed fine radicular processes projecting from the endothelium, differing from the MCT1-immunonegative filopodia. These findings suggest that the expression of nutrient transporters in the ocular blood vessels is differentially regulated at a cellular level and that the neonatal eyes provide an interesting model for research on nutrient transporters in the endothelium. (C) 2016 Elsevier Ltd. All rights reserved.
  • Benjamin Bonneau, Hideaki Ando, Katsuhiro Kawaai, Matsumi Hirose, Hiromi Takahashi-Iwanaga, Katsuhiko Mikoshiba
    ELIFE 5 2016年12月 [査読有り][通常論文]
     
    IRBIT is a molecule that interacts with the inositol 1,4,5-trisphosphate (IP3)-binding pocket of the IP3 receptor (IP3R), whereas the antiapoptotic protein, Bcl2l10, binds to another part of the IP3-binding domain. Here we show that Bcl2l10 and IRBIT interact and exert an additive inhibition of IP3R in the physiological state. Moreover, we found that these proteins associate in a complex in mitochondria-associated membranes (MAMs) and that their interplay is involved in apoptosis regulation. MAMs are a hotspot for Ca2+ transfer between endoplasmic reticulum (ER) and mitochondria, and massive Ca2+ release through IP3R in mitochondria induces cell death. We found that upon apoptotic stress, IRBIT is dephosphorylated, becoming an inhibitor of Bcl2l10. Moreover, IRBIT promotes ER mitochondria contact. Our results suggest that by inhibiting Bcl2l10 activity and promoting contact between ER and mitochondria, IRBIT facilitates massive Ca2+ transfer to mitochondria and promotes apoptosis. This work then describes IRBIT as a new regulator of cell death.
  • Mami Mutoh, Shunsuke Kimura, Hiromi Takahashi-Iwanaga, Meri Hisamoto, Toshihiko Iwanaga, Junichiro Iida
    CELL AND TISSUE RESEARCH 364 1 175 - 184 2016年04月 [査読有り][通常論文]
     
    Murine nasopharynx-associated lymphoid tissue (NALT), located at the base of the nasal cavity, serves as a major site for the induction of mucosal immune responses against airway antigens. The follicle-associated epithelium (FAE) covering the luminal surface of NALT is characterized by the presence of microfold cells (M cells), which take up and transport luminal antigens to lymphocytes. Glycoprotein 2 (GP2) has recently been identified as a reliable marker for M cells in Peyer's patches of the intestine. However, the expression of GP2 and other functional molecules in the M cells of NALT has not yet been examined. We have immunohistochemically detected GP2-expressing cells in the FAE of NALT and the simultaneous expression of other intestinal M-cell markers, namely Tnfaip2, CCL9, and Spi-B. These cells have been further identified as M cells because of their higher uptake capacity of luminal microbeads. Electron microscopic observations have shown that GP2-expressing cells on the FAE display morphological features typical of M cells: they possess short microvilli and microfolds on the luminal surface and are closely associated with intraepithelial lymphocytes. We have also found that the receptor activator of nuclear factor kappa-B ligand (RANKL) is expressed by stromal cells underneath the FAE, which provides its receptor RANK. The administration of RANKL markedly increases the number of GP2(+)Tnfaip2(+) cells on the NALT FAE and that of intestinal M cells. These results suggest that GP2(+)Tnfaip2(+) cells in NALT are equivalent to intestinal M cells, and that RANKL-RANK signaling induces their differentiation.
  • Chihiro Hisatsune, Etsuko Ebisui, Masaya Usui, Naoko Ogawa, Akio Suzuki, Nobuko Mataga, Hiromi Takahashi-Iwanaga, Katsuhiko Mikoshiba
    MOLECULAR CELL 58 6 1015 - 1027 2015年06月 [査読有り][通常論文]
     
    Blood pressure maintenance is vital for systemic homeostasis, and angiotensin II is a critical regulator. The upstream mechanisms that regulate angiotensin II are not completely understood. Here, we show that angiotensin II is regulated by ERp44, a factor involved in disulfide bond formation in the ER. In mice, genetic loss of ERp44 destabilizes angiotensin II and causes hypotension. We show that ERp44 forms a mixed disulfide bond with ERAP1, an aminopeptidase that cleaves angiotensin II. ERp44 controls the release of ERAP1 in a redox-dependent manner to control blood pressure. Additionally, we found that systemic inflammation triggers ERAP1 retention in the ER to inhibit hypotension. These findings suggest that the ER redox state calibrates serum angiotensin II levels via regulation of the ERp44-ERAP1 complex. Our results reveal a link between ER function and normotension and implicate the ER redox state as a potential risk factor in the development of cardiovascular disease.
  • Kohtarou Konno, Hiromi Takahashi-Iwanaga, Motokazu Uchigashima, Kyoko Miyasaka, Akihiro Funakoshi, Masahiko Watanabe, Toshihiko Iwanaga
    HISTOCHEMISTRY AND CELL BIOLOGY 143 3 301 - 312 2015年03月 [査読有り][通常論文]
     
    Information concerning the cellular localization of cholecystokinin (CCK)-1 receptors has been discrepant and remained scanty at ultrastructural levels. The present immunohistochemical study at light and electron microscopic levels revealed the distinct localization of CCK1 receptors in visceral organs. Immunohistochemistry by use of a purified antibody against mouse CCK1 receptor was applied to fixed tissue sections of the pancreas, gallbladder, stomach, and intestine of mice. A silver-intensified immunogold method revealed the subcellular localization under electron microscope. The immunoreactivity for CCK1 receptors was selectively found in the basolateral membrane of pancreatic acinar cells and gastric chief cells but was absent in pancreatic islets and gastric D cells. Another intense expression in the gut was seen in the myenteric nerve plexus of the antro-duodenal region and some populations of c-Kit-expressing pacemaker cells in the duodenal musculature. The gallbladder contained smooth muscle fibers with an intense immunoreactivity of CCK1 receptors on cell surfaces. The restricted localization of CCK1 receptors on the basolateral membrane of pancreatic acinar cells and gastric chief cells, along with their absence in the islets of Langerhans and gastric D cells, provides definitive information concerning the regulatory mechanism by circulating CCK. Especially, the subcellular localization in the acinar cells completes the investigation for the detection of circulating CCK by the basolateral membrane.
  • Kimura S, Kishimoto A, Mutoh M, Takahashi-Iwanaga H, Iwanaga T
    Biomedical research (Tokyo, Japan) 36 4 263 - 272 2015年 [査読有り][通常論文]
  • Hiromi Takahashi-Iwanaga
    BIOMEDICAL RESEARCH-TOKYO 36 5 331 - 341 2015年 [査読有り][通常論文]
     
    The renal glomeruli in lower vertebrates display mesangium-like cells and matrices interposed between the capillary endothelium and the basement membrane, while those in mammals reportedly lack such interpositions except in pathological conditions. By combined scanning and transmission electron microscopic observations, the pericapillary mesangial tissues were comparatively analyzed in four vertebrate classes: mammals (rats and rabbits), reptiles (green iguanas), amphibians (bullfrogs), and teleosts (carps). The observations discriminated three types of pericapillary interposition. The first, acellular interpositions, occurred universally, with mammalians displaying rudimental ones. This tissue type corresponded with extracellular matrices held in subendothelial grooves which were supported by fine endothelial projections anchored to the basement membrane. In lower vertebrates these grooves constituted an anastomosed system of subendothelial channels that communicated with the mesangial region, to favor cleaning of the glomerular filter. The second, compound type was specific to reptiles and amphibians, affecting the entire capillary circumference in the latter. In this tissue type, fine mesangial processes-which accompanied considerable amounts of fibrillar matrices-were loosely associated with the endothelial bases, indicating their possible nature as a kind of myofibroblast. Occurrence of the third, cellular interpositions was confined to small incidental loci in mammalian and teleost glomeruli. This tissue type was mostly occupied by thick processes or main bodies of the mesangial cells that tightly interlocked their short marginal microvilli with corresponding indentations on the endothelial bases.
  • Miao Zheng, Shunsuke Kimura, Junko Nio-Kobayashi, Hiromi Takahashi-Iwanaga, Toshihiko Iwanaga
    BIOMEDICAL RESEARCH-TOKYO 35 1 37 - 45 2014年02月 [査読有り][通常論文]
     
    Immunohistochemistry using whole mount preparations of the murine mesentery revealed two types of LYVE-1-immunoreactive cells with dendritic morphology other than F4/80(+) typical macrophages. The two types of LYVE-1(+) cells were regularly distributed with constant intervals throughout the mesentery and appeared to possess their own territory. Both types of LYVE-1(+) cells were weakly or moderately immunopositive for F4/80 antibody, a marker of macrophages, while F4/80(+) round macrophages were absolutely free from the LYVE-1 immunoreactivity. Only macrophages could ingest latex particles of 20 nm in diameter 3 h after a peritoneal injection. Peritoneal administration of lipopolysaccharide (LPS) induced a rapid reduction of LYVE-1 immunoreactivity in the cells with dendritic morphology followed by an increased immunoreactivity to F4/80 antibody, and simultaneously by dynamic changes in their shape. Under nonnal conditions, F4/80(+) macrophages in various connective tissues expressed LYVE-1, in contrast to lack of LYVE-1 in F4/80(+) macrophages within the parenchyma of visceral organs and macrophages residing in hepatic sinusoids and pulmonary alveoli. LYVE-1 may play a role in cell adhesion and migration of macrophagic cells within connective tissues rich in hyaluronan, and loss of LYVE-1 becomes a reliable sign of activated conditions in inflammation.
  • Hiromi Takahashi-Iwanaga
    BIOMEDICAL RESEARCH-TOKYO 34 1 51 - 60 2013年02月 [査読有り][通常論文]
     
    We have previously shown the duct system in the rat pancreas to consist of two parts: a fine proximal (intercalated) duct and thicker distal (intralobular and interlobular) duct, with the latter part displaying morphological signs indicative of a bicarbonate-rich fluid secretion. In this study the pancreatic duct system in the Japanese monkey Macaca fuscata was observed by scanning electron microscopy after the hydrolytic exposure of cell surfaces as well as by transmission electron microscopy of ultrathin sections. Cellular expression of the water channel aquaporin 1 (AQP1) was also examined immunohistochemically. In contrast to the segmented duct system in the rat, all the duct cells in the monkey pancreas consistently displayed rich mitochondria in the cytoplasm, elaborate interdigitations of cell processes, and an intense immunoreactivity for AQP1 on the apical and basolateral cell membrane to favor active ion transport and osmotic water movement across the epithelium. Both the existence of secretory canaliculi and basal trabeculae in the duct epithelium and randomized localization of primary cilia on the luminal cell surfaces were demonstrated for the first time in monkeys, and the physiological implications of these phenomena are discussed.
  • Mai Sato-Miyaoka, Chihiro Hisatsune, Etsuko Ebisui, Naoko Ogawa, Hiromi Takahashi-Iwanaga, Katsuhiko Mikoshiba
    JOURNAL OF INVESTIGATIVE DERMATOLOGY 132 9 2137 - 2147 2012年09月 [査読有り][通常論文]
     
    Here we showed that the type 3 IP3 receptor (IP(3)R3) is specifically expressed in hair follicles of the skin and plays an important role in the regulation of the hair cycle. We found that IP(3)R3-deficient (Itpr3(-/-)) mice had prominent alopecia, which was characterized by repeated hair loss and regrowth. The alopecic stripe runs along the body axis like a wave, suggesting disturbed hair-cycle regulation. Indeed, the hair follicles of the alopecic region were in the early anagen stage. Although the hair growth and proliferation activity of the hair matrix cells in the anagen phase were normal in Itpr3(-/-) mice, telogen club hairs in the telogen-anagen transition phase were loosely attached to the hair follicles and were easily removed in contrast to the more tightly attached club hairs of Itpr3(+/+) mice. Itpr3(-/-) keratinocytes surrounding the telogen club hairs have sparse cytokeratin filaments extending in random directions, as well as less developed desmosomes. Furthermore, nuclear factor of activated T cells c1 (NFATc1) failed to translocate into the nucleus of keratin 6-positive bulge cells in Itpr3(-/-) telogen follicles. We propose that hair shedding is actively controlled by the IP(3)R3/NFAT-dependent signaling pathway, possibly through the regulation of cytokeratin filaments in keratinocytes.
  • Hiromi Takahashi-Iwanaga, Toshihiko Iwanaga
    JOURNAL OF COMPARATIVE NEUROLOGY 520 9 2053 - 2066 2012年06月 [査読有り][通常論文]
     
    The terminal Schwann cells that accompany lanceolate sensory endings in the rat vibrissal follicle are known to display the small plasma membrane invaginations termed caveolae, which concentrate Ca2+ signaling molecules. We have previously shown that these cells generate Ca2+ signals at the lamellar processes covering the receptor axons through activation of the metabotropic purinoceptor P2Y2. To investigate the roles of caveolae in the spatiotemporal organization of Ca2+ signals, terminal Schwann cells were observed by immunohistochemistry for the caveola protein caveolin-1, and by transmission and scanning electron microscopy. In addition, immunohistochemical detection of P2Y2 and its coupling partner Gq/11 along with confocal image analysis of the purinergically induced glial Ca2+ responses was performed in isolated tissue preparations either treated or untreated with the caveolae eliminator methyl-beta-cyclodextrin. Results showed the Schwann lamellae to be characterized by the presence of dense caveolae accompanying a fine tubular network of the endoplasmic reticulum Ca2+ store and by intense expression of the signaling molecules P2Y2 and Gq/11. Loss of caveolae diffusely redistributed these molecules throughout the entire cell and impaired the lamellar Ca2+ signals, both in chronological priority (preceding the global cell response) and in spatial integrity (involving the entire length of the processes). To our knowledge, this is the first report of a subcellular accumulation of caveolae underlying compartmentalized glial Ca2+ signals that can couple with local effects on the accompanying axon terminals. J. Comp. Neurol. 520:20532066, 2012. (c) 2011 Wiley Periodicals, Inc.
  • Kumiko Takebe, Hiromi Takahasi-Iwanaga, Toshihiko Iwanaga
    BIOMEDICAL RESEARCH-TOKYO 32 4 293 - 301 2011年08月 [査読有り][通常論文]
     
    Monocarboxylates-lactate and ketone bodies can compensate for glucose as energy sources under certain physical conditions. To identify the main energy source used in self-renewing tissues, expression profiles of monocarboxylate transporters (MCTs) were mainly investigated immunohistochemically in the gastrointestinal tract, skin, and bone marrow of mice, with reference to glucose transporters. In the small intestine, MCTI-immunoreactive epithelial cells accumulated in crypts with a selective immunolabeling along the basolateral membrane of cells. BrdU-labeled dividing cells were included in the cryptal MCTI-immunoreactive foci. The skin displayed an intense and extensive immunoreactivity for MCT1 in the hair bulge, which gives rise to the epidermis, hair, and sebaceous gland. The stratified squamous epithelium in the esophagus contained MCT1-immunoreactive cells in the basal layer but frequently lacked GLUT1-immunoreactive cells. The bone marrow was largely immunoreactive for MCT1 but not for GLUT I, suggesting the active production and utilization of monocarboxylates for hematopoiesis under hypoxic conditions. These findings support the idea that monocarboxylates are favorite energy sources in self-renewing tissues.
  • Toshihiko Iwanaga, Yasukazu Hozumi, Hiromi Takahashi-Iwanaga
    BIOMEDICAL RESEARCH-TOKYO 32 3 225 - 235 2011年06月 [査読有り][通常論文]
     
    Dopamine regulates the synthesis and secretion of prolactin and alpha-MSH/beta-endorphin in lactotrophs and melanotrophs, respectively. While a predominant dopamine receptor, D2R, is known to be expressed in both the anterior and intermediate lobes of the pituitary gland, no previous immunohistochemical studies have shown the existence of D2R in the plasma membrane of pituitary endocrine cells. The present study clearly demonstrated a selective localization of the D2R immunoreactivity in primary cilia of lactotrophs and melanotrophs in the mouse adenohypophysis. Another immunoreactivity of D2R was found along the plasma membrane of melanotrophs. The intensity of immunoreactivity for D2R in the primary cilia of lactrotrophs changed during the estrous cycle and with genital conditions in contrast to a consistent immunolabeling in the melanotrophs. Since there is accumulating evidence that the primary cilium functions as a sensory device at a cellular level, the D2R-expressing primary cilia in the pituitary gland may be involved in the sensation of dopamine and dopaminergic compounds though their involvement differs between the anterior and intermediate lobes.
  • Takuya Kuchiiwa, Junko Nio-Kobayashi, Hiromi Takahashi-Iwanaga, Takaji Yajima, Toshihiko Iwanaga
    HISTOCHEMISTRY AND CELL BIOLOGY 135 4 351 - 360 2011年04月 [査読有り][通常論文]
     
    The present study examined the cellular localization of monocarboxylate transporters (MCTs), glucose transporters (GLUTs), and some glycolysis-related molecules in the murine female genital tract to demonstrate existence of lactate/pyruvate-dependent energy systems. MCT1, a major MCT subtype, was localized selectively in the ovarian granulosa, oviductal-ciliated cells, and vaginal epithelium; all localizations were associated with intense expressions of glycolytic enzymes. MCT1 was localized in the cell membrane of granulosa cells, including fine processes extending from cumulus cells toward oocytes. The cumulus cells and oocytes showed intense signals for lactate dehydrogenase (LDH)-A and -B, respectively. The basolateral membrane of oviductal-ciliated cells expressed MCT4 as well as MCT1, while adjacent non-ciliated cells contained an intense immunoreactivity for aldolase-C, a glycolytic enzyme. The expression of GLUTs in the ovary was generally weak with an intense expression of GLUT1 only in some vascular endothelia. The oviductal epithelium expressed GLUT1 and GLUT3, respectively, in the basolateral and apical membrane of non-ciliated cells. In the vagina, the basal layers of epithelium were immunolabeled for MCT1 with the entire length of cell membrane, and expressed abundantly both GLUT1 and LDH-A. The findings correspond well with the rich existence of lactate in the genital fluids and strongly suggest the active transport of lactate/pyruvate in the female reproductive tract, which provides favorable conditions for oocytes, sperms, and zygotes.
  • Toshihiko Iwanaga, Takashi Miki, Hiromi Takahashi-Iwanaga
    BIOMEDICAL RESEARCH-TOKYO 32 1 73 - 81 2011年02月 [査読有り][通常論文]
     
    The primary cilium is now considered to function as a fundamental, not rudimentary, structure for mechanical and chemical sensing by individual cells. Primary cilia in neurons express type III adenylyl cyclase (ACIII) and GPCRs for somatostatin (somatostatin receptor 3, SSTR3), serotonin, and melanin-concentrating hormone. The present immunohistochemical and electron microscopic study revealed an abundant occurrence of SSTR3-expressing solitary cilia in insulin- and growth hormone-secreting cells of the mouse. The SSTR3 immunoreactivity was restricted to the plasma membrane of cilia in both cell types, differing from previously reported immunohistochemical localization of SSTRs to cell bodies. The primary cilia in the islet cells were longer than those in the pituitary cells and extended for a long distance in the intercellular canalicules endowed with microvilli. No other endocrine organs were provided with the SSTR3-expressing primary cilia, while the primary cilia in these organs were frequently immunolabeled with ACIII antibody. Since the somatostatin inhibition of both insulin and GH release is regulated mainly by SSTR1 and SSTR5, the primary cilia expressing SSTR3 may be involved in a signaling which differs from that via other SSTR subtypes expressing in cell bodies.
  • Akihiro Inagaki, Soichiro Yamaguchi, Hiromi Takahashi-Iwanaga, Toshihiko Iwanaga, Toru Ishikawa
    JOURNAL OF MEMBRANE BIOLOGY 235 1 27 - 41 2010年05月 [査読有り][通常論文]
     
    ClC-2, a member of the voltage-gated Cl- channel family, is expressed in the distal colonic surface epithelial cells of various species, but its functional significance remains unclear. Here, by means of electrophysiological and molecular biological techniques, we have identified and characterized a ClC-2-like conductance naturally expressed by surface epithelial cells acutely dissociated from rectal colon of rats fed a standard diet. Whole-cell patch-clamp experiments showed that the surface cells, whether an amiloride-sensitive Na+ conductance was present or not, displayed a strong hyperpolarization-activated, inwardly rectifying Cl- current. Analysis both by in situ hybridization and immunohistochemistry confirmed the expression of ClC-2 in the rectal surface epithelium. The native Cl- current shared common electrophysiological properties including voltage-dependent activation, anion selectivity sequence, and Zn2+ sensitivity with that recorded from HEK293 cells transfected with ClC-2 cloned from rat rectal colon (rClC-2). Cell-attached patch recordings on the surface cells revealed that native ClC-2-like currents activated only at potentials at least 40 mV more negative than resting membrane potentials. In Ussing chamber experiments with rat rectal mucosa, either basolateral or apical application of Zn2+ (0.1 mM), which inhibited both native ClC-2-like currents and recombinant rClC-2 currents, had little, if any, effects on basal amiloride-sensitive short-circuit current. Collectively, these results not only demonstrate that a functional ClC-2-type Cl- channel is expressed in rat rectal surface epithelium, but also suggest that the channel activity may be negligible and thus nonessential for controlling electrogenic Na+ transport in this surface epithelium under basal physiological conditions.
  • A. Nagai, K. Takebe, J. Nio-Kobayashi, H. Takahashi-Iwanaga, T. Iwanaga
    PLACENTA 31 2 126 - 133 2010年02月 [査読有り][通常論文]
     
    Lactate plays an important role as an alternative energy substrate, especially in conditions with a decreased utility of glucose Proton-coupled monocarboxylate transporters (MCTs) are essential for the transport of lactate, ketone bodies, and other monocarboxylates through the plasma membrane and may contribute to the net transport of lactate through the placental barrier The present study examined the expression profile and subcellular localization of MCTs in the mouse placenta. An in situ hybridization survey of all MCT subtypes detected intense mRNA expressions of MCT1, MCT4, and MCT9 as well as GLUT1 in the placenta from gestational day 115. The expression of MCT mRNAs decreased in the intensity at the end of gestation in contrast to a consistently intense expression of GLUT1 mRNA. Immunohistochemically, MCT1 and MCT4 showed a polarized localization on the maternal side and fetal side of the two cell-layered syncytiotrophoblast, respectively. The membrane-oriented localization of MCTs was supported by the coexistence of CD147 which recruits MCT to the plasma membrane However, the subcellular arrangement of MCT1 and MCT4 along the trophoblastic cell membrane was completely opposite of that in the human placenta Although we cannot exactly explain the reversed localization of MCTs between human and murine placentas, it may be related to differences between humans and mice in the origin of lactate and its utilization by fetuses (C) 2009 Elsevier Ltd. All rights reserved
  • Kumiko Takebe, Junko Nio-Kobayashi, Hiromi Takahashi-Iwanaga, Takaji Yajima, Toshihiko Iwanaga
    HISTOCHEMISTRY AND CELL BIOLOGY 131 3 401 - 409 2009年03月 [査読有り][通常論文]
     
    Proton-coupled monocarboxylate transporters (MCTs) are essential for the transport of lactate, ketone bodies, and other monocarboxylates through the plasma membrane, but the direction and substrates of transporting in loco remain unclear. The present study examined the expression and subcellular localization of MCTs in lipogenic organs. An in situ hybridization survey of major MCT subtypes detected an intense expression of MCT1 mRNA in the mammary gland, Harderian gland, and sebaceous gland. The MCT1 immunoreactivity was found baso-laterally in acinar cells of the mammary and Harderian glands. Alveolar cells of sebaceous glands in the skin, eyelids, and penis contained the membrane-associated MCT1 immunoreactivity along the entire length of the cell surface at the margin of alveoli. These MCT1-expressing exocrine glands possessed more abundant transcripts of acetyl-CoA carboxylase-1, a key enzyme for lipogenesis, than did representative lipogenetic organs such as the liver. Since the secretions from these glands contain fat as a major product, the cellular localization of MCT1 suggests the involvement of the transporter in the uptake of lactate, acetate, and other monocarboxylates for production of medium- and long-chain fatty acids.
  • Junko Nio-Kobayashi, Hiromi Takahashi-Iwanaga, Toshihiko Iwanaga
    JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY 57 1 41 - 50 2009年01月 [査読有り][通常論文]
     
    Galectin, an animal lectin that recognizes beta-galactoside of glycoconjugates, is abundant in the gut, This IHC study showed the subtype-specific localization of galectin in the mouse digestive tract. Mucosal epithelium showed region/cell-specific localization of each galectin subtype. Gastric mucous cells exhibited intense immunoreactions for galectin-2 and galectin-4/6 with a limited localization of galectin-3 at the surface of the gastric mucosa. Electron microscopically, galectin-3 immunoreactivity coated indigenous bacteria on the gastric surface mucous cells. Epithelial cells in the small intestine showed characteristic localizations of galectin-2 and galectin-4/6 in the cytoplasm of goblet cells and the baso-lateral membrane of enterocytes in association with maturation, respectively. Galectin-3 expressed only at the villus tips was concentrated at the myosin-rich terminal web of fully matured enterocytes. Epithelial cells of the large intestine contained intense immunoreactions for galectin-3 and galectin-4/6 but not for galectin-2. The stratified squamous epithelium of the forestomach was immunoreactive for galectin-3 and galectin-7, but the basal layer lacked galectin-3 immunoreactivity. Outside the epithelium, only galectin-1 was localized in the connective tissue, smooth muscles, and neuronal cell bodies. The subtype-specific localization of galectin suggests its important roles in host-pathogen interaction and epithelial homeostasis such as membrane polarization and trafficking in the gut. (J Histochem Cytochem 57:41-50, 2009)
  • Kumiko Takebe, Junko Nio-Kobayashi, Hiromi Takahashi-Iwanaga, Toshihiko Iwanaga
    BIOMEDICAL RESEARCH-TOKYO 29 6 297 - 306 2008年12月 [査読有り][通常論文]
     
    Peripheral nerves express GLUT1 in both endoneurial blood vessels and the perineurium and utilize glucose as a major energy Substrate, as does the brain. However, under conditions of a reduced utilization of glucose., the brain is dependent upon monocarboxylates such as ketone bodies and lactate, being accompanied by an elevated expression of a monocarboxylate transporter (MCTI) in the blood-brain barrier. The present immunohistochemical study aimed to examine the expression or MCTI in the peripheral nerves of mice. MCTI immunoreactivity was found in the perineurial sheath and colocalized with GLUT1, while the endoneurial blood vessels expressed GLUT1 only. An intense expression of MCT1 in the perineurium was confirmed by Western blot and in situ hybridization analyses. Ultrastructurally, the MCTI and GLUT1 immunoreactivities in the thick perineurium showed an intensity gradient decreasing towards the innermost layer. In neonates, the MCT1 immunoreactivity in the perineurium was intense, while the GLUT1 immunoreactivity was faint or absent. These findings suggest that peripheral nerves depend oil rnonocarboxylates as a major energy source and that MCTI in the perineurium is responsible for the supply of rnonocarboxylates to nerve fibers and Schwann cells.
  • Hiromichi Ishikawa, Tomoaki Naito, Toshihiko Iwanaga, Hiromi Takahashi-Iwanaga, Makoto Suematsu, Toshifumi Hibi, Masanobu Nanno
    IMMUNOLOGICAL REVIEWS 215 154 - 165 2007年02月 [査読有り][通常論文]
     
    The alimentary tract has an epithelial layer, consisting mainly of intestinal epithelial cells (IECs), that is exposed to the exterior world through the intestinal lumen. The IEC layer contains many intestinal intraepithelial T cells (IELs), and the total number of IELs constitutes the largest population in the peripheral T-cell pool. Virtually all gamma delta-IELs and many alpha beta-IELs in the mouse small intestine are known to express CD8 alpha alpha homodimers. A wide range of evidence that supports extrathymic development of these CD8 alpha alpha(+) IELs has been collected. In addition, while several studies identified cells with precursor T-cell phenotypes within the gut epithelium, how these precursors, which are dispersed along the length of the intestine, develop into gamma delta-IELs and/or alpha beta-IELs has not been clarified. The identification of lymphoid cell aggregations named 'cryptopatches' (CPs) in the intestinal crypt lamina propria of mice as sites rich in T-cell precursors in 1996 by our research group, however, provided evidence for a central site, whereby precursor IELs could give rise to T-cell receptor-bearing IELs. In this review, we discuss the development of IELs in the intestinal mucosa and examine the possibility that CPs serve as a production site of extrathymic IELs.
  • H Takahashi-Iwanaga, Y Habara
    JOURNAL OF COMPARATIVE NEUROLOGY 475 3 416 - 425 2004年07月 [査読有り][通常論文]
     
    The longitudinal lanceolate endings are mechanoreceptors that detect hair movement. We have previously shown that terminal Schwann cells, glial elements of the sensory devices, respond to an application of the sensory modulator adenosine 5'-triphosphate (ATP) by an elevation in the intracellular Ca2+ concentration ([Ca2+](i)), suggesting a regulatory role for these cells in the cutaneous sensation. To define the spatiotemporal dynamics of the cell signaling and the pharmacological properties of the receptors responsible, arrays of the lanceolates were enzymatically isolated from the rat vibrissal follicle and subjected to [Ca2+](i) image recording by time-lapse confocal microscopy during bath application of ATP analogues. The terminal Schwann cells formed extensive networks, connecting with one another by their lamellar processes associated with lanceolate axon endings. Stimulation of the cells with 100 muM ATP evoked [Ca2+](i) waves propagating along the cell processes. In each Schwann lamella, the initial wave evoked by a given trial of the stimulant arose from a specific locus within the cell process, whereas subsequent waves were sometimes observed to travel from its proximal portion. This implies a subcellular compartmentalization that may enable each Schwann lamella to modulate the activity of its accompanying lanceolate terminal through its own Ca2+ signal as well as to regulate neighboring lanceolates through interlamellar signal propagation. Pharmacological experiments have shown that the Schwann cell responses are mediated by the P2Y(2) receptor, which has recently been reported to couple to multiple effector molecules in addition to stimulating the phosphoinositide signaling pathway involved in various glia-neuron interactions. (C) 2004 Wiley-Liss, Inc.
  • H Takahashi-Iwanaga, Y Habara
    NEUROSCIENCE LETTERS 324 2 137 - 140 2002年05月 [査読有り][通常論文]
     
    Extracellular adenosine 5-triphosphate (ATP) has been known to mediate and modulate cutaneous sensations. We examined the effect of this substance on isolated terminal Schwann cells associating with lanceolate endings, the mechanoreceptors of rat vibrissae. The free intracellular calcium concentration ([Ca2+](i)) of the sensory device was monitored by digital image microscopy in combination with a calcium-sensitive fluorescent probe, Fura-2. Application of ATP in concentrations raging from 10 muM to 1 mM evoked an increase in [Ca2+](i) in Schwann cell processes covering the lancet-like axon terminals as well as in round perikarya of the cells protruding from the terminals. In both portions, the ATP-evoked [Ca2+](i) elevations were slowly oscillatory at 10 and 20 muM, and continuous at concentrations higher than 50 muM. Suramin 100 muM blocked the effect of ATP. Uridine 5'-triphosphate was equipotent with ATP, while alpha,beta-methylene ATP was ineffective. These data indicate that the terminal Schwann cells express P2Y purinoceptors linked with the intracellular Ca2+ signaling, and that this phenomenon is involved in the ATP-mediated sensory modulation. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
  • Hamada H, Hiroi T, Nishiyama Y, Takahashi H, Masunaga Y, Hachimura S, Kaminogawa S, Takahashi-Iwanaga H, Iwanaga T, Kiyono H, Yamamoto H, Ishikawa H
    Journal of immunology (Baltimore, Md. : 1950) 168 1 57 - 64 2002年01月 [査読有り][通常論文]
  • H Oguma, G Murakami, H Takahashi-Iwanaga, M Aoki, S Ishii
    JOURNAL OF ORTHOPAEDIC RESEARCH 19 5 873 - 880 2001年09月 [査読有り][通常論文]
     
    To clarify the early process of recovery at the bone-tendon interface, we used light microscopy and SEM to examine the process of anchoring of collagen fibers to bone in a canine model. At two weeks, tendon. sear tissue, woven bone and lamellar bone were present at the insertion site. SEM revealed anchoring of collagen fibril bundles of the scar to the woven bone. By 4 weeks, the number of anchoring fibers had increased and a parallel arrangement of fibers was observed. SEM demonstrated deep penetration of fibers into the woven bone layer. In addition, the fibers were observed to project into and intermingle with the scar tissue. By 6 weeks, the anchoring fibers had developed fully and were distributed densely over the interface. SEM also revealed that the collagen fibril bundles in the sear tissue had connected with the collagen fibrils of the woven bone by way of the anchoring bundles. The woven bone was identifiable throughout the early stages of recovery as the interface between soft tissue and hard tissue. Throughout all experimental periods, no staining was observed at the interface of the tendon and bone by Saffranin-O. The formation of woven bone was important during early recovery of the tendon-bone interface prior to the completion of fibrocartilage-mediated insertion. (C) 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
  • Takahashi-Iwanaga H
    Italian journal of anatomy and embryology = Archivio italiano di anatomia ed embriologia 106 2 Suppl 1 481 - 487 2001年 [査読有り][通常論文]
  • K Mori, H Takahashi-Iwanaga, T Iwanaga
    JAPANESE JOURNAL OF VETERINARY RESEARCH 48 2-3 137 - 146 2000年11月 [査読有り][通常論文]
     
    We found frequent and unique parasitism by an unidentified myxosporean in the kidney of the arctic lamprey, Lampetra japonica, living in Japan. Trophozoites (pseudoplasmodia with or without sporoblasts) existed predominantly in the lumina of proximal urinary tubules, but were rarely found in any other regions of the kidney. Since no mature spores were produced in the trophozoites, exact identification of the species was impossible. Two parasitic forms were recognized in proximal urinary tubules : one adhering to the epithelial cells of renal tubules, and the other free-floating in the lumina of tubules. Ultrastructurally, the attaching trophozoites developed microvilli-like projections towards the apical surface of epithelial cells and vigorously interdigitated with microvilli of the brush border. In contrast, the whole surface of the floating trophozoite was smooth without any cell projections. The developed projections in the former type of trophozoite may contribute to their firm attachment to the epithelial cells and/or to absorption of nutrients via the epithelial cells. Against the myxosporean infection, the lamprey as the host exhibited a local immune reaction by disposition of numerous lymphocytes and macrophages into the epithelium of urinary tubules.
  • Kawamura T, Toyabe S, Moroda T, Iiai T, Takahashi-Iwanaga H, Fukada M, Watanabe H, Sekikawa H, Seki S, Abo T
    Hepatology (Baltimore, Md.) 26 6 1567 - 1572 1997年12月 [査読有り][通常論文]
  • Murate M, Kishimoto Y, Sugiyama T, Fujisawa T, Takahashi-Iwanaga H, Iwanaga T
    Journal of cell science 110 ( Pt 16) 1919 - 1934 1997年08月 [査読有り][通常論文]
  • Orikasa M, Iwanaga T, Takahashi-Iwanaga H, Kozima K, Shimizu F
    Laboratory investigation; a journal of technical methods and pathology 75 5 719 - 733 1996年11月 [査読有り][通常論文]
  • Y Kawachi, K Arai, T Moroda, T Kawamura, H Umezu, M Naito, K Ohtsuka, K Hasegawa, H TakahashiIwanaga, LD Shultz, H Watanabe, T Abo
    EUROPEAN JOURNAL OF IMMUNOLOGY 25 12 3452 - 3459 1995年12月 [査読有り][通常論文]
     
    Extrathymic T cells exist in the liver and are often seen in close contact with Kupffer cells in the hepatic sinusoids. Since selective depletion of Kupffer cells has became possible by using liposome-encapsulated clodronate, it was investigated whether elimination of Kupffer cells influences the level of extrathymic T cells in the liver. Extrathymic T cells were identified as interleukin-2 receptor beta-chain (IL-2R beta) intermediate TCR (TCR(int)) cells by two-color staining for CD3 or T cell receptor (TCR) and IL-2R beta. The elimination of Kupffer cells did not significantly affect levels of TCR(int) cells up to 7 days after treatment. We then examined monocyte colony stimulating factor (M-CSF)-deficient op/op mice (low levels of Kupffer cells). Extrathymic T cells both in the liver and spleen of these mice were detected at a level comparable to that of control mice. Since extrathymic T cells in the liver are sometimes located in the parenchymal space, the relationship between extrathymic T cells and hepatocytes was then examined. Electron microscopy revealed that some hepatic T cells adhered directly to hepatocytes. When hepatocytes were damaged by a single injection of CCl4, hepatocyte death and subsequent hepatic fibrosis were induced. Beginning 3 days after injection, CD3(int) cells, but not other type of cells, decreased prominently. Purified CD3(int) cells, as well as whole lymphocytes in the liver, were cytotoxic against syngeneic hepatoma. In parallel with the above-mentioned hepatic damage, the cytotoxic activity of lymphocytes against such targets was impaired in the liver. These results suggest that extrathymic generation of TCR(int) cells and their acquisition of cytotoxic function are relatively independent of Kupffer cells, but are dependent on hepatocytes.
  • Watanabe H, Miyaji C, Kawachi Y, Iiai T, Ohtsuka K, Iwanage T, Takahashi-Iwanaga H, Abo T
    Journal of immunology (Baltimore, Md. : 1950) 155 6 2972 - 2983 1995年09月 [査読有り][通常論文]
  • T IWANAGA, O HOSHI, HX HAN, H TAKAHASHIIWANAGA, Y UCHIYAMA, T FUJITA
    ARCHIVES OF HISTOLOGY AND CYTOLOGY 57 3 267 - 276 1994年08月 [査読有り][通常論文]
     
    In the rat small intestine, apoptotic enterocytes are exfoliated at the villus tip as a whole cell, in contrast to guinea pig enterocytes which are phagocytosed by macrophages in their cell body and shed off only in their apical cortex. While macrophages gather in the lamina propria of the intestinal villi in both species, their functions seem to differ. Unlike the guinea pig, lamina propria macrophages observed in the rat small intestine did not show morphological signs of phagocytosis, revealing few cellular elements in their phagosomes. At the ''shoulder'' of the villus, i.e., a certain distance proximal to the villus tip, subepithelial macrophages extended a thick process deep into the epithelium; their branched terminals penetrated the cytoplasm of enterocytes, resulting in the formation of excavated spaces in the cell body. Processes of macrophages frequently reached close to the brush border. At the shoulder of the villus, a few effete cells showed typical apoptotic signs and appeared to be pushed out into the lumen; still, the shedding of apoptotic enterocytes was recognized mainly at the very top of the villus, where no intraepithelial processes of macrophages could be seen. The present findings indicate that in the rat, lamina propria macrophages do not engulf aged enterocytes, but are involved in inducing their apoptosis.
  • M SAEKI, H TAKAHASHIIWANAGA, T IWANAGA, T FUJITA, M KODAMA, H HANAWA, SS ZHANG, T IZUMI, A SHIBATA
    TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE 172 3 195 - 204 1994年03月 [査読有り][通常論文]
     
    Our previous study reported the rich existence of multinucleated giant cells in an autoimmune myocarditis experimentally induced in rats. The present study investigated the histochemical and ultrastructural characteristics of these giant cells. Histochemistry for an acid phosphatase clearly demonstrated multinucleated giant cells dispersed at the inflammatory foci. Ultrastructurally, the giant cells were shown to be single cells, but not clustered cells. Their ultrastructural characteristics were very similar to the basic features of macrophages, except that the giant cells mere poor in lysosomes and phagosomes. It was noticeable that some macrophages possessed three or more nuclei, displaying an intermediate form between mononuclear macrophages and multinucleated giant cells. These findings suggest that the giant cell in the experimental autoimmune myocarditis is a single multinucleated cell, and possibly derived from macrophages by cell-to-cell fusion.
  • T IIAI, H WATANABE, S SEKI, K SUGIURA, K HIROKAWA, M UTSUYAMA, H TAKAHASHIIWANAGA, T IWANAGA, T OHTEKI, T ABO
    IMMUNOLOGY 77 4 556 - 563 1992年12月 [査読有り][通常論文]
     
    We previously demonstrated that the liver may be a major site of extrathymic T-cell differentiation in mice. In the present study, the ontogeny and subsequent development of such T cells in the liver and other organs were investigated. This study was possible because these T cells have T-cell receptors (TcR) of intermediate intensity (i.e. intermediate TcR cells) and constitutively express a high level of interleukin-2 receptor beta chain (IL-2Rbeta). Therefore the two-colour staining for CD3 (or alphabeta TcR) and IL-2Rbeta identifies even a small proportion of intermediate TcR cells. The total numbers of mononuclear cells obtained from the liver, thymus and spleen varied from foetal to adult life. Especially in the liver, many haematopoietic cells were present in the parenchymal space at the foetal stage. There were no lymphocytes in the sinusoidal lumen at this period. In contrast, lymphocytes appeared in the hepatic sinusoids after birth and increased with ageing. Phenotypic analysis revealed that intermediate TcR cells appeared in the liver and spleen on Day 4 after birth. Bright TcR cells of thymic origin were also present in the peripheral organs on Day 4. Thereafter, intermediate TcR cells increased in the liver, whereas bright TcR cells increased in the periphery as a function of age. Similarly, thymectomized and congenitally athymic mice had mainly intermediate TcR cells in the liver and, to some extent, periphery. It is concluded that intermediate TcR cells, possibly of extrathymic origin, are generated only after birth and expand with ageing.
  • M TERADA, T IWANAGA, H TAKAHASHIIWANAGA, ADACHI, I, M ARAKAWA, T FUJITA
    ARCHIVES OF HISTOLOGY AND CYTOLOGY 55 3 219 - 233 1992年07月 [査読有り][通常論文]
     
    The airway mucosa is known to be densely supplied with several types of peptidergic nerve fibers. The distribution of the nerve fibers in a large extent of the mucosa, however, has been difficult to visualize by observation of conventional thin sections. In the present study, whole mount preparations of the rat tracheal mucosa were designed to demonstrate calcitonin gene-related peptide (CGRP)-containing nerves which are most predominant among peptidergic nerves in the trachea. The mucosal sheet of the trachea was separated from the cartilaginous base by means of dispase, a protease, to be processed to immunohistochemistry for CGRP. In the cartilaginous portion, thick nerve bundles immunoreactive for CGRP ran transversely between the cartilage rings, sending terminal branches toward the epithelium. In the membranous portion, immunoreactive nerve bundles were thinner than those in the cartilaginous portion and ran longitudinally. A very dense nerve plexus of CGRP-immunoreactive fibers was demonstrated to extend in the basal part of the epithelium; every epithelial cell appeared to contact more than one nerve fiber. Immunohistochemistry of the whole mount preparations also clearly demonstrated the distribution and entire shape of broncho-pulmonary paraneurons scattered in the epithelium. Ultrastructurally, the CGRP-immunoreactive intraepithelial nerves were found to lack myelin and Schwann sheaths, and to run through the bases of the epithelial cells; they were most frequently surrounded by the cytoplasmic processes of the epithelial cells. The present study demonstrates that immunohistochemistry of whole mount preparations is a useful tool to morphologically analyze neuronal and paraneuronal distribution throughout the tracheal epithelium.
  • Takahashi-Iwanaga H
    Archives of histology and cytology 55 Suppl 147 - 155 1992年 [査読有り][通常論文]
  • H KONDO, H TAKAHASHIIWANAGA, H ABE, M WATANABE, Y TAKAHASHI
    ARCHIVES OF HISTOLOGY AND CYTOLOGY 54 4 437 - 445 1991年10月 [査読有り][通常論文]
     
    By means of peroxidase-anti-peroxidase (PAP) immunohistochemistry with both the neurofilament (NF) triplet (small: 68 K, medium: 150 K, high: 200 K) antisera and the antiserum against spot 35-calbindin, developmental changes in expression of the immunoreactivity for the NF triplet proteins in different domains of the Purkinje cells was examined in the cerebella of postnatal rats. From birth till the postnatal day 6 (P6) the somata and dendrites exhibited moderately positive immunoreaction for small and medium NF subunits. In contrast, the incubation for the high NF subunit resulted in a negative immunoreaction for the somata and dendrites of the Purkinje cells at those stages. On P8 and P10 they were weakly immunoreactive for all NF triplet. Thereafter the intensity of their immunoreaction decreased progressively and the Purkinje cell somata and dendrites were immunonegative for all NF triplet proteins on P21, when the Purkinje cell attained an adult appearance in morphology. On the other hand, the Purkinje cell axons, which can be identified selectively by the positive immunoreaction for the spot 35-calbindin throughout the course of the postnatal development, exhibited positive immunoreactivity for all the NF triplet on the 9th, 21th and 50th postnatal days in the cerebellar white matter. The development of the slow axoplasmic transport and the posttranslational modification of the NF triplet proteins are discussed as possible mechanisms underlying the differential expression of the immunoreactivity for the NF triplet proteins in different domains of the Purkinje cells during postnatal development.
  • T SHINTANI, T FUSHIKI, S FUKUOKA, H TAKAHASHIIWANAGA, E SUGIMOTO
    FEBS LETTERS 255 2 423 - 426 1989年09月 [査読有り][通常論文]
  • Takahashi-Iwanaga H
    Progress in clinical and biological research 295 203 - 212 1989年 [査読有り][通常論文]

MISC

  • Haruko Yanase, Kumiko Takebe, Junko Nio-Kobayashi, Hiromi Takahashi-Iwanaga, Toshihiko Iwanaga HISTOCHEMISTRY AND CELL BIOLOGY 130 (5) 957 -966 2008年11月 [査読無し][通常論文]
     
    Expression analysis of transporters selective for monocarboxylates such as lactate and ketone bodies in the kidney contributes to understanding the renal energy metabolism. Distribution and expression intensity of a sodium-dependent monocarboxylate transporter (SMCT) and proton-coupled monocarboxylate transporters (MCT) were examined in the mouse kidney. In situ hybridization survey detected significant mRNA expressions of SMCT and MCT-1, 2, 5, 8, 9, 10, and 12. Among these, signals for SMCT, MCT2 and MCT8 were predominant; transcripts of SMCT were restricted to the cortex and the outer stripe of outer medulla, while those of MCT2 and MCT8 gathered in the inner stripe of outer medulla and the cortex, respectively. Immunohistochemically, SMCT was present at the brush border in S2 and S3 of proximal tubules, suggesting the active uptake of luminal monocarboxylates here. MCT1 and MCT2 immunoreactivities were respectively found baso-laterally in S1 and thick ascending limbs of Henle's loop. The cellular localization of transporters suggests the involvement of SMCT in the uptake of filtrated lactate and ketone bodies and that of MCTs in the transport of monocarboxylate metabolites between tubular cells and circulation, but the different distribution patterns do not support the notion of a functional linkage between SMCT and MCT1/MCT2.
  • Hiromi Takahashi-Iwanaga, Junko Nio-Kobayashi, Yoshiaki Habara, Kishio Furuya JOURNAL OF COMPARATIVE NEUROLOGY 510 (1) 68 -78 2008年09月 [査読無し][通常論文]
     
    The lanceolate sensory endings that form palisades around the hair follicle associate with networks of branched Schwann cells. To define the properties of these glial networks as possible conduits of Ca(2+) signals, lanceolate endings isolated from rat vibrissae were observed by confocal microscopy while the signaling was locally activated by mechanical stimulation. Intercellular coupling by gap junctions was also assessed by a technique employing fluorescence recovery after photobleaching (FRAP) and by transmission electron microscopy (TEM). Results showed that the glial Ca(2+) signals can spread among the arrays of lanceolates in two forms: rapid signals that originate in individual Schwann processes covering the lanceolate axon terminals around the locus of mechanical stimulation, and delayed ones that travel from the stimulation locus through cytoplasmic arborization of the primarily activated cell to the adjacent cell processes. The former signaling was suppressed by the antipurinergic agents suramin and apyrase, whereas the latter was sensitive to the gap junction blocker carbenoxolon. FRAP experiments and TEM observations corroborated the presence of gap junction communications between the Schwann processes of different cell origins. These findings show that, in the Schwann networks, purinergically induced Ca(2+) signals and those dependent on gap junctions are propagated in their own spatiotemporal patterns to constitute two distinct forms of communication among the mechanoreceptor palisades.
  • Chihiro Hisatsune, Keiko Yasumatsu, Hiromi Takahashi-Iwanaga, Naoko Ogawa, Yukiko Kuroda, Ryusuke Yoshida, Yuzo Ninomiya, Katsuhiko Mikoshiba JOURNAL OF BIOLOGICAL CHEMISTRY 282 (51) 37225 -37231 2007年12月 [査読無し][通常論文]
     
    Inositol 1,4,5-trisphosphate receptor (IP3R) is one of the important calcium channels expressed in the endoplasmic reticulum and has been shown to play crucial roles in various physiological phenomena. Type 3 IP3R is expressed in taste cells, but the physiological relevance of this receptor in taste perception in vivo is still unknown. Here, we show that mice lacking IP(3)R3 show abnormal behavioral and electrophysiological responses to sweet, umami, and bitter substances that trigger G-protein-coupled receptor activation. In contrast, responses to salty and acid tastes are largely normal in the mutant mice. We conclude that IP3R3 is a principal mediator of sweet, bitter, and umami taste perception and would be a missing molecule linking phospholipase C beta 2 to TRPM5 activation.
  • Junko Nio, Hiromi Takahashi-Iwanaga, Masami Morimatsu, Yasuhiro Kon, Toshihiko Iwanaga Histochemistry and Cell Biology 126 (1) 45 -56 2006年07月 [査読無し][通常論文]
     
    Galectin is an animal lectin that has high affinity to β-galactoside of glycoconjugates. In the present study, cellular expression of galectin subtypes in the urinary system of adult mice was examined by in situ hybridization and immunohistochemistry. The major subtype expressed in the murine urinary system was galectin-3, which was expressed continuously from the kidney to the distal end of the urethra. The renal cortex expressed galectin-3 more intensely than the medulla. Renal galectin-3 immunoreactivity was strongest in the cortical collecting ducts, where principal cells were the sole cellular source. All cell layers of the transitional epithelium from the renal pelvis to the urethra strongly expressed galectin-3 at the mRNA and protein levels. An electron microscopic study demonstrated diffuse cytoplasmic localization of galectin-3 in principal cells of the collecting ducts and in the bladder epithelial cells. Urethral galectin-3 expression at the pars spongiosa decreased in intensity near the external urethral orifice, where the predominant subtype of galectin was substituted by galectin-7. The muscular layer of the ureter and urinary bladder contained significant signals for galectin-1. Taken together, the observations indicate that the adult urinary system shows intense and selective expression of galectin-3 in epithelia of the uretic bud- and cloaca-derivatives. © Springer-Verlag 2006.
  • A Futatsugi, T Nakamura, MK Yamada, E Ebisui, K Nakamura, K Uchida, T Kitaguchi, H Takahashi-Iwanaga, T Noda, J Aruga, K Mikoshiba SCIENCE 309 (5744) 2232 -2234 2005年09月 [査読無し][通常論文]
     
    Type 2 and type 3 inositol 1,4,5-trisphosphate receptors (IP3 R2 and IP(3)R3) are intracellular calcium-release channels whose physiological roles are unknown. We show exocrine dysfunction in IP3 R2 and IP3 R3 double knock-out mice, which caused difficulties in nutrient digestion. Severely impaired calcium signaling in acinar cells of the salivary glands and the pancreas in the double mutants ascribed the secretion deficits to a tack of intracellular calcium release. Despite a normal caloric intake, the double mutants were hypoglycemic and lean. These results reveal IP3 R2 and IP3 R3 as key molecules in exocrine physiology underlying energy metabolism and animal growth.
  • Calcium signaling in terminal Schwann cells associated with lanceolate sensory endings in rat vibrissae.
    Ital J Anat Embryol 110 (suppl.1 19-24) 2005年 [査読無し][通常論文]
  • Calcium signaling in termninal Schwann cells associated with lanceolate sensory endings in rat vibrissae.
    Ital J Anat Embryol 110 (suppl.1 19-24) 2005年 [査読無し][通常論文]
  • J Neurocytol 32, 363-371 2003年 [査読無し][通常論文]
  • 知覚終末シュワン細胞のCa信号系-とくにラット頰ひげ毛包の槍型終末について-
    脳の科学 25 (9) 893 -898 2003年 [査読無し][通常論文]
  • J Neurocytol 32, 363-371 2003年 [査読無し][通常論文]
  • Hiromi Takahashi-Iwanaga Microscopy Research and Technique 57 (4) 196 -202 2002年05月15日 [査読無し][通常論文]
     
    The three-dimensional structure of the renal glomerular podocyte was comparatively analyzed with special reference to its cellular interdigitation. Kidneys of lampreys, carps, eels, xenopuses, bullfrogs, iguanas, rats, and rabbits were used as materials. Urinary and basal surfaces of podocytes were exposed by a conventional freeze-fracture method and by NaOH maceration, respectively, and subsequently examined by scanning electron microscopy. In accordance with previous reports, each podocyte consisted of a round cell body protruding into Bowman's space, four to six major processes embracing glomerular capillary, and numerous pedicels on both sides of the major processes. The podocyte pedicels exhibited uniform needle-like shapes, about 0.2 μm thick, interdigitated with those of adjoining cells along the entire length of the cell margins in all the animal species examined. This finding suggests that the fine pedicel interdigitation is a primary event in morphogenesis of the podocyte. The basal aspect of the glomerular epithelium was mosaicked with pedicels which were laid at various angles to the capillary axis, in favor of its possible role as a mechanical support of the capillary wall. © 2002 Wiley-Liss, Inc.
  • H Takahashi-Iwanaga MICROSCOPY RESEARCH AND TECHNIQUE 57 (4) 196 -202 2002年05月 [査読無し][通常論文]
     
    The three-dimensional structure of the renal glomerular podocyte was comparatively analyzed with special reference to its cellular interdigitation. Kidneys of lampreys, carps, eels, xenopuses, bullfrogs, iguanas, rats, and rabbits were used as materials. Urinary and basal surfaces of podocytes were exposed by a conventional freeze-fracture method and by NaOH maceration, respectively, and subsequently examined by scanning electron microscopy. In accordance with previous reports, each podocyte consisted of a round cell body protruding into Bowman's space, four to six major processes embracing glomerular capillary, and numerous pedicels on both sides of the major processes. The podocyte pedicels exhibited uniform needle-like shapes, about 0.2 mum thick, interdigitated with those of adjoining cells along the entire length of the cell margins in all the animal species examined. This finding suggests that the fine pedicel interdigitation is a primary event in morphogenesis of the podocyte. The basal aspect of the glomerular epithelium was mosaicked with pedicels which were laid at various angles to the capillary axis, in favor of its possible role as a mechanical support of the capillary wall. (C) 2002 Wiley-Liss, Inc.
  • 走査電顕が示す足突起のモザイク状配列
    医学のあゆみ 198 (10) 703 2001年 [査読無し][通常論文]
  • Hiromi Takahashi-Iwanaga, Kazuhiro Abe Acta Anatomica Nipponica 76 (4) 375 -380 2001年 [査読無し][通常論文]
     
    The Merkel cell in the epidermis has generally been regarded as a mechanoreceptor which detects tissue deformations with its microvilli, and subsequently releases certain transmitters to nerve endings. In order to analyze the mechanism of mechanoreception, the fine structure of lamprey Merkel cells and their relationships with surrounding tissue were examined by scanning electron microscopy (SEM) after exposure of the cells by NaOH maceration, as well as by transmission electron microscopy (TEM) according to a conventional method. By SEM, lamprey Merkel cells revealed small round cell bodies bearing numerous microvilli on the upper and lower poles in accord with previous TEM reports. Combined SEM and TEM observations showed that the Merkel cell bodies were tightly held in corresponding concavities of other epidermal cells, with some desmosomes connecting the cells with each other. On the other hand, microvilli of the Merkel cells extended freely in intercellular spaces bound with complex microplicae of epidermal cells. The regional difference in mechanical anchorage of the Merkel cells probably leads to transient deflection and subsequent recovery of their microvilli during a given mechanical stimulation, suggesting rapidly adapting mechanoreception by the cells.
  • H Takahashi-Iwanaga, MJ Kim, K Abe, Y Habara BIOMEDICAL RESEARCH-TOKYO 21 (5) 283 -290 2000年10月 [査読無し][通常論文]
     
    Acetylcholine has been known to potentiate secretin-stimulated bicarbonate secretion by the pancreatic duct system. Recent studies have shown that this phenomenon is at least partially attributable to the agonist-induced elevation of intracellular Ca2+ concentration ([Ca2+](i)) in pancreatic duct cells. In order to define spatiotemporal dynamics of these [Ca2+](i) signals, short segments of intralobular and interlobular ducts were isolated from the rat pancreas and examined by digital image microscopy using a calcium-sensitive, fluorescent probe, Fura-2. In accord with previous reports by microspectrofluorometry, duct segments stimulated with carbachol consistently displayed [Ca2+](i) rises, which were specifically suppressed by atropine. Present image analyses additionally demonstrated a fine fluctuate unevenness of the [Ca2+](i) level in the duct epithelium during the stimulation, suggesting an asynchronous oscillatory mode of response of the pancreatic duct cells.
  • H Takahashi-Iwanaga JOURNAL OF COMPARATIVE NEUROLOGY 426 (2) 259 -269 2000年10月 [査読無し][通常論文]
     
    The longitudinal lanceolate endings are ubiquitous sensory terminals in the sinus and nonsinus hairs of mammals that form a palisade around the hair follicle. To analyze how the nerve endings detect hair movements, the present study re-examined their fine structure and relationships with surrounding connective tissue in rat vibrissae by using a combination of three methods: immunohistochemistry for S-100 protein, scanning electron microscopy of NaOH-macerated specimens, and transmission electron microscopy of serial sections. Observations showed the lanceolate endings to be represented by triplet units with a flattened axon terminal flanked on each side by a Schwann cell lamella, as reported previously. Two distinct Darts were discriminated in the lanceolate ending: a principal. portion in which the axon terminal protruded numerous fine fingers from between the Schwann cell coverings, and an apical cone that enclosed a large axon finger in an attenuated Schwann sheath. Long foot processes of Schwann cells fanned out distally from each apical cone. The principal portions of the lanceolate endings were firmly linked to the surrounding connective tissue by the narrow edges equipped with axon fingers, suggesting their continuous deformation by sustained hair deflections. In contrast, the apical cones were freely suspended in an amorphous matrix with only the end feet of the Schwann cell projections attached to rigid tissue elements. This part of the ending was proposed as a possible transducer site to generate rapidly adapting receptor potentials, both retreating and overshooting during the acceleration and deceleration phases of a given vibrissal movement. (C) 2000 Wiley-Liss, Inc.
  • Parasitic forms of a myxosporean in the kidney of the arctic lamprey, Lamptera Japonica : an ultrastructural study
    Jpn J Vet Res 48 137 -146 2000年 [査読無し][通常論文]
  • Hiromi TAKAHASHI-IWANAGA, Toshihiko IWANAGA, Haruhiko ISAYAMA Arch Histol Cytol 62 (5) 471 -481 1999年 [査読無し][通常論文]
  • H Takahashi-Iwanaga, T Murakami, K Abe JOURNAL OF NEUROCYTOLOGY 27 (11) 817 -827 1998年11月 [査読無し][通常論文]
     
    Spinal motor neurons possess reticular coats of extracellular matrix proteoglycans on their somata and proximal dendrites. In order to define the anatomical background of the network, spatial relationships of the perineuronal proteoglycans with synaptic boutons and astrocyte processes were analyzed in rat motor neurons by TEM after histochemical detection of the substances with cationic iron colloid, and by SEM after exposure of the cytoarchitecture with NaOH maceration. Narrow intercellular channels filled with proteoglycan were found to extend along the surface of the neurons to form a homogeneous network of a mesh size of about 1 mu m. The system of perineuronal channels consisted of two parts: a primary intervaricose net which meandered among synaptic boutons on the surface of the motor neuron, and secondary subvaricose nets which irrigated interfaces between larger boutons and the neuron. No elements in the perineuronal cytoarchitecture coincided with the meshwork of proteoglycan, indicating the involvement of postsynaptic factors in the distribution of the substance. Thin astrocyte processes surrounding the neurons formed a distinct network with heterogeneous meshes corresponding to boutons of various sizes. The perineuronal glial nets extended their surface area in contact with the intervaricose nets of proteoglycan by complex cellular interdigitations. The subvaricose nets of proteoglycan compartmentalized multiple synapses on large boutons, suggesting an involvement in the division of the synapses during development.
  • H Saito, Y Kanamori, T Takemori, H Nariuchi, E Kubota, H Takahashi-Iwanaga, T Iwanaga, H Ishikawa SCIENCE 280 (5361) 275 -278 1998年04月 [査読無し][通常論文]
     
    Cryptopatches (CPs) are part of the murine intestinal immune compartment, Cells isolated from CPs of the small intestine that were c-kit positive (c-kit(+)) but lineage markers negative (Lin(-)) gave rise to T cell receptor (TCR) alpha beta and TCR gamma delta intestinal intraepithelial T cells after in vivo transfer or tissue engraftment into severe combined immunodeficient mice. In contrast, cells from Peyer's patches and mesenteric lymph nodes, which belong in the same intestinal immune compartment but lack c-kit(+)Lin(-) cells, failed lo do so, These findings and results of electron microscopic analysis provide evidence of a local intestinal T cell precursor that develops in the CPs.
  • 歯根膜ルフィニ神経終末をみる
    ザ・クインテッセンス 17 3 -8 1998年 [査読無し][通常論文]
  • 腎実質と尿路の上皮細胞形態-尿沈渣像理解のために
    メディカル・テクノロジー 26 856 -857 1998年 [査読無し][通常論文]
  • M Fukuda, T Moroda, S Toyabe, T Iiai, Y Kawachi, H TakahashiIwanaga, T Iwanaga, M Okada, T Abo BIOMEDICAL RESEARCH-TOKYO 17 (2) 171 -181 1996年04月 [査読無し][通常論文]
     
    Since the incidence of acute appendicitis seems to vary with weather, we investigated the underlying mechanism. When 112 patients who had undergone appendectomy were classified into three groups according to atmospheric pressure at the time of onset, gangrenous cases (high infiltration of granulocytes) were much greater in frequency than catarrhal cases (no infiltration of granulocytes) at high pressure, At low pressure, the situation was the reverse. The variation of granulocytes and lymphocytes in the blood as related to atmospheric pressure and heart rate was examined in healthy donors. Granulocytosis was seen with increased sympathetic activity (high heart rate) at high pressure, whereas lymphocytosis was seen with increased parasympathetic activity (low heart rate) at low pressure. Taken together with the results from patients, in which gangrenous cases showed granulocytosis in the blood as well as in the appendix while catarrhal cases showed lymphocytosis in the blood and appendix, it is presumed that granulocytosis induced by increased sympathetic activity might be related to the onset of gangrenous appendicitis. Experimental results using human and mouse materials indicated that catecholamines induce granulocytosis via their adrenergic receptors. Even in gangrenous cases, bacteria were not detected in the vicinity of granulocytes in the appendix by electron microscopy. The present results seem to shed important light on the etiology of suppurative diseases.
  • 腸上皮細胞の更新に関与する上皮内リンパ球
    病理と臨床 14 (7) 875 -880 1996年 [査読無し][通常論文]
  • 尿細管上皮細胞の走査電顕像
    細胞 28 (6) 228 -232 1996年 [査読無し][通常論文]
  • Macrophagic cells out growth from normal rat giomerular culture ; possible metaplastic change from podocytes.
    Lab Invest 75 (5) 719 -733 1996年 [査読無し][通常論文]
  • Cell Tissue Res 283,455-459 1996年 [査読無し][通常論文]
  • Ultrastructural and time-lapse observations of intraepithelial lymphocytes in the small intestine of the guinea pig : their possible role in the removal of effete enterocytes.
    Cell Tissue Res 280,491-497 1995年 [査読無し][通常論文]
  • Scanning electron microscopy of the muscle system of ┣DBHydra magnipapillata(/)-┫DB
    Cell Tissue Res 277,79-86 1994年 [査読無し][通常論文]
  • 神経終末の立体構造、走査電顕が示す中枢神経系軸索終末の多様性
    医学のあゆみ 165 149 1993年 [査読無し][通常論文]
  • ニューロンとパラニューロンの構造と信号伝達機能
    クリニカル・ニューロサイエンス 11 273 -276 1993年 [査読無し][通常論文]
  • Scanning electron microscopy of the cerebellar cortex of rats : An application of the NaOH maceration method
    Acta Medica et Biologica 42,25-29 1993年 [査読無し][通常論文]
  • SEM observation of mesangial cells in the rat kidney by NaOH maceration combined with freeze cracking.
    Acta Medica et Biologica 39 37 -44 1991年 [査読無し][通常論文]
  • The three-dimensional cytoarchitecture of the interstitial tissue in the rat kidney.
    Cell Tissue Res. 264 1991年 [査読無し][通常論文]
  • Arch . Histol. Cytol. 54 (4) 455 -464 1991年 [査読無し][通常論文]
  • H TAKAHASHIIWANAGA, T FUJITA, M TAKEDA ARCHIVES OF HISTOLOGY AND CYTOLOGY 53 (Suppl) 189 -197 1990年 [査読無し][通常論文]
  • Yuka IWATA, Kazuo ADACHI, Tsuneo FUJITA, Hiromi TAKAHASHI-IWANAGA Arch. Histol. Cytol. 52 (4) 395 -405 1989年 [査読無し][通常論文]
  • H TAKAHASHIIWANAGA, H KONDO, T YAMAKUNI, Y TAKAHASHI DEVELOPMENTAL BRAIN RESEARCH 29 (2) 225 -231 1986年10月 [査読無し][通常論文]
  • Hiromi TAKAHASHI-IWANAGA, Tsuneo FUJITA Arch. Histol. Jpn. 49 (3) 349 -357 1986年 [査読無し][通常論文]
  • H TAKAHASHIIWANAGA, T FUJITA CELL AND TISSUE RESEARCH 242 (1) 57 -66 1985年 [査読無し][通常論文]

書籍等出版物

  • The Merkel Cell, Structure-Development-Function-cancerogenesis.
    Springer, Berlin・Heidelberg 2003年
  • The Merkel Cell, Structure-Development-Function-cancerogenesis.
    Springer, Berlin・Heidelberg 2003年
  • 分子糖尿病学の進歩.基礎から臨床まで
    金原出版,東京 1997年
  • Human Mummies. A Global Survey of their Status and the Techniques of Conservation.
    Springer, Wien 1996年
  • The three-dimensional structure of renal tubule cells.
    Cells and Tissues : A Three-Dimensional Approach 1989年

所属学協会

  • 日本リンパ学会   日本解剖学会   

共同研究・競争的資金等の研究課題

  • 機械受容器の立体微細構造
  • 腎髄質間質の立体構造と種差
  • 中枢神経系シナプスの立体構造の多様性
  • The three-dimensional ultrastructure of mechanoreceptors.
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