Updated on 2022/05/17

写真a

 
KOMURO, Terumasa
 
Affiliation
Faculty of Human Sciences
Job title
Professor Emeritus

Education

  •  
    -
    1964

    東京教育大学   理学部   生物  

Degree

  • Kyushu University   Dr. of Medical Science

Research Experience

  • 1991
    -
     

    - 早稲田大学人間科学部 教授

  • 1991
    -
     

    - Professor

  • 1973
    -
    1991

    Ehime University   School of Medicine

  • 1973
    -
    1991

    Associate Professor

  • 1968
    -
    1973

    Kyushu University   School of Medicine

  • 1968
    -
    1973

    Research Assistant

  • 1965
    -
    1968

    Niigata University   Faculty of Medicine

  • 1965
    -
    1968

    Research Assistant

▼display all

Professional Memberships

  •  
     
     

    国際自律神経学会(ISAN)

  •  
     
     

    日本平滑筋学会

  •  
     
     

    日本解剖学会

  •  
     
     

    日本顕微鏡学会

 

Research Areas

  • Anatomy

Research Interests

  • 組織学

  • Embryology)

  • Anatomy in General (incl.Histology

  • Histology

Misc

  • Three-dimensional demonstration of the interstitial cells of Cajal associated with the submucosal plexus in guinea-pig caecum

    Hiromi Tamada, Terumasa Komuro

    CELL AND TISSUE RESEARCH   344 ( 1 ) 183 - 188  2011.04

     View Summary

    The guinea-pig caecum was studied by using immunohistochemistry for Kit receptors and nerves to clarify whether interstitial cells of Cajal (ICC) were localized in association with the submucosal plexus (ICC-SP). A large area of the guinea-pig caecum was nearly devoid of longitudinal muscles, because they were concentrated into three bundles of the taenia caeci (coli) and this allowed clear observation of the myenteric and submucosal plexus as separate networks in whole-mount stretch preparations. The myenteric plexus was observed as a loose polygonal network consisting in elongated ganglia and long connecting nerve strands, whereas the submucosal plexus was identified as smaller ovoid ganglia connected to much thinner nerve strands in different tissue layers. Three-dimensional reconstruction of confocal images revealed multipolar-shaped ICC-SP located around the submucosal ganglion in a basket formation. Bipolar ICC-SP were also observed along the connecting nerve strands of the submucosal plexus. The functional involvement of ICC-SP in mucosal activity is discussed in relation to fluid transportation. This three-dimensional study of ICC-SP thus provides a candidate for the most suitable material available for functional experiments examining the physiological significance of ICC-SP.

    DOI

  • Three-dimensional demonstration of the interstitial cells of Cajal associated with the submucosal plexus in guinea-pig caecum

    Hiromi Tamada, Terumasa Komuro

    CELL AND TISSUE RESEARCH   344 ( 1 ) 183 - 188  2011.04

     View Summary

    The guinea-pig caecum was studied by using immunohistochemistry for Kit receptors and nerves to clarify whether interstitial cells of Cajal (ICC) were localized in association with the submucosal plexus (ICC-SP). A large area of the guinea-pig caecum was nearly devoid of longitudinal muscles, because they were concentrated into three bundles of the taenia caeci (coli) and this allowed clear observation of the myenteric and submucosal plexus as separate networks in whole-mount stretch preparations. The myenteric plexus was observed as a loose polygonal network consisting in elongated ganglia and long connecting nerve strands, whereas the submucosal plexus was identified as smaller ovoid ganglia connected to much thinner nerve strands in different tissue layers. Three-dimensional reconstruction of confocal images revealed multipolar-shaped ICC-SP located around the submucosal ganglion in a basket formation. Bipolar ICC-SP were also observed along the connecting nerve strands of the submucosal plexus. The functional involvement of ICC-SP in mucosal activity is discussed in relation to fluid transportation. This three-dimensional study of ICC-SP thus provides a candidate for the most suitable material available for functional experiments examining the physiological significance of ICC-SP.

    DOI

  • Distribution and morphological characteristics of the interstitial cells of Cajal in the ileocaecal junction of the guinea-pig

    Sachiko Miyamoto-Kikuta, Taichi Ezaki, Terumasa Komuro

    CELL AND TISSUE RESEARCH   338 ( 1 ) 29 - 35  2009.10

     View Summary

    The guinea-pig ileocaecal junction including the valve was studied by immunohistochemistry to clarify the organization of the muscle bundles, the enteric nerves and the interstitial cells of Cajal (ICC). This region clearly exhibited characteristic features in the distribution patterns of ICC in a proximal to distal direction: (1) the thickened portion of the terminal ileum immediately adjacent to the ileocecal junction contained many ICC throughout the circular (ICC-CM) and longitudinal (ICC-LM) muscle layers, but ICC were few or absent in the rest of the ileum; (2) the ileal side of the valve contained ICC associated with the deep muscular plexus (ICC-DMP) as in the small intestine, whereas ICC-DMP were absent in the caecal side as in the caecum; (3) the valve contained many ICC-CM and ICC-LM in both the ileal and caecal sides; (4) many ICC associated with the myenteric plexus were observed in both the ileal and caecal sides of the valve, whereas they were only sparsely found in the caecum; (5) ICC were also observed around the submucosal plexus in a confined area of the terminal ileum and the ileocaecal valve. These observations provide morphological evidence that the terminal ileum and ileocaecal valve are specially equipped for their active involvement in the movement of the junctional area.

    DOI

  • Distribution and morphological characteristics of the interstitial cells of Cajal in the ileocaecal junction of the guinea-pig

    Sachiko Miyamoto-Kikuta, Taichi Ezaki, Terumasa Komuro

    CELL AND TISSUE RESEARCH   338 ( 1 ) 29 - 35  2009.10

     View Summary

    The guinea-pig ileocaecal junction including the valve was studied by immunohistochemistry to clarify the organization of the muscle bundles, the enteric nerves and the interstitial cells of Cajal (ICC). This region clearly exhibited characteristic features in the distribution patterns of ICC in a proximal to distal direction: (1) the thickened portion of the terminal ileum immediately adjacent to the ileocecal junction contained many ICC throughout the circular (ICC-CM) and longitudinal (ICC-LM) muscle layers, but ICC were few or absent in the rest of the ileum; (2) the ileal side of the valve contained ICC associated with the deep muscular plexus (ICC-DMP) as in the small intestine, whereas ICC-DMP were absent in the caecal side as in the caecum; (3) the valve contained many ICC-CM and ICC-LM in both the ileal and caecal sides; (4) many ICC associated with the myenteric plexus were observed in both the ileal and caecal sides of the valve, whereas they were only sparsely found in the caecum; (5) ICC were also observed around the submucosal plexus in a confined area of the terminal ileum and the ileocaecal valve. These observations provide morphological evidence that the terminal ileum and ileocaecal valve are specially equipped for their active involvement in the movement of the junctional area.

    DOI

  • Characterization of interstitial cells of Cajal in the subserosal layer of the guinea-pig colon

    Hiromi Aranishi, Yumi Kunisawa, Terumasa Komuro

    CELL AND TISSUE RESEARCH   335 ( 2 ) 323 - 329  2009.02

     View Summary

    Interstitial cells of Cajal in the subserosa (ICC-SS) of the guinea-pig proximal colon were studied by immunohistochemistry for c-Kit receptors and by transmission electron microscopy. These cells were distributed within a thin layer of connective tissue space immediately beneath the mesothelium and were multipolar with about five primary cytoplasmic processes that divided further into secondary and tertiary processes to form a two-dimensional network. Ultrastructural observations revealed that ICC-SS were connected to each other via gap junctions. They also formed close contacts and peg-and-socket junctions with smooth muscle cells. Three-dimensional analysis of confocal micrographs revealed that the cytoplasmic processes of ICC-SS had contacts with interstitial cells in the longitudinal muscle layer. Taking account of the location and peculiar arrangement of the ICC-SS and the main functions of the proximal colon, i.e. the absorption and transport of fluids, we suggest that the superficial network of ICC-SS acts as a stretch receptor to detect circumferential expansion and swelling of the colon wall and triggers the contraction of the longitudinal muscle to accelerate the drainage of fluids from the colon.

    DOI

  • Characterization of interstitial cells of Cajal in the subserosal layer of the guinea-pig colon

    Hiromi Aranishi, Yumi Kunisawa, Terumasa Komuro

    CELL AND TISSUE RESEARCH   335 ( 2 ) 323 - 329  2009.02

     View Summary

    Interstitial cells of Cajal in the subserosa (ICC-SS) of the guinea-pig proximal colon were studied by immunohistochemistry for c-Kit receptors and by transmission electron microscopy. These cells were distributed within a thin layer of connective tissue space immediately beneath the mesothelium and were multipolar with about five primary cytoplasmic processes that divided further into secondary and tertiary processes to form a two-dimensional network. Ultrastructural observations revealed that ICC-SS were connected to each other via gap junctions. They also formed close contacts and peg-and-socket junctions with smooth muscle cells. Three-dimensional analysis of confocal micrographs revealed that the cytoplasmic processes of ICC-SS had contacts with interstitial cells in the longitudinal muscle layer. Taking account of the location and peculiar arrangement of the ICC-SS and the main functions of the proximal colon, i.e. the absorption and transport of fluids, we suggest that the superficial network of ICC-SS acts as a stretch receptor to detect circumferential expansion and swelling of the colon wall and triggers the contraction of the longitudinal muscle to accelerate the drainage of fluids from the colon.

    DOI

  • Interstitial cells of Cajal associated with the submucosal plexus of the Guinea-pig stomach

    Yumi Kunisawa, Terumasa Komuro

    NEUROSCIENCE LETTERS   434 ( 3 ) 273 - 276  2008.04

     View Summary

    Interstitial cells of Cajal (ICC) form specialized networks in the gastrointestinal tract that coordinate cellular communications between nerves and smooth muscle cells. However, little is known about ICC in the gut mucosa or submucosa. Here, we report for the first time that Kit-immunoreactive ICC are associated with the submucosal (Meissner's) plexus of the Guinea-pig stomach. In longitudinal sections along the greater curvature of the gastric corpus, short spindle-shaped ICC of the submucosal plexus (ICC-SP) were located around the PGP9.5-immunoreactive nerve elements in the submucosa. Observations of whole-mount preparations clearly demonstrated Kit-immunoreactive bipolar or multipolar cells with long cytoplasmic processes about 100 mu m in length. Such cells had typical characteristics of ICC, confirming that they were not mast cells, which are also Kit-immunoreactive residents of the submucosal connective tissue space. Although some ICC-SP surrounded parts of the submucosal plexus, they did not appear to form wide extensions of the cellular network, suggesting that they acted locally. The demonstration of ICC-SP in the submucosal connective tissue space suggests that they may contribute to the regulation of secretion, absorption and transportation of fluids in the mucosa. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

    DOI

  • Interstitial cells of Cajal associated with the submucosal plexus of the Guinea-pig stomach

    Yumi Kunisawa, Terumasa Komuro

    NEUROSCIENCE LETTERS   434 ( 3 ) 273 - 276  2008.04

     View Summary

    Interstitial cells of Cajal (ICC) form specialized networks in the gastrointestinal tract that coordinate cellular communications between nerves and smooth muscle cells. However, little is known about ICC in the gut mucosa or submucosa. Here, we report for the first time that Kit-immunoreactive ICC are associated with the submucosal (Meissner's) plexus of the Guinea-pig stomach. In longitudinal sections along the greater curvature of the gastric corpus, short spindle-shaped ICC of the submucosal plexus (ICC-SP) were located around the PGP9.5-immunoreactive nerve elements in the submucosa. Observations of whole-mount preparations clearly demonstrated Kit-immunoreactive bipolar or multipolar cells with long cytoplasmic processes about 100 mu m in length. Such cells had typical characteristics of ICC, confirming that they were not mast cells, which are also Kit-immunoreactive residents of the submucosal connective tissue space. Although some ICC-SP surrounded parts of the submucosal plexus, they did not appear to form wide extensions of the cellular network, suggesting that they acted locally. The demonstration of ICC-SP in the submucosal connective tissue space suggests that they may contribute to the regulation of secretion, absorption and transportation of fluids in the mucosa. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

    DOI

  • Ultrastructural observations of the tunica muscularis in the small intestine of Xenopus laevis, with special reference to the interstitial cells of Cajal

    Sachiko Miyamoto-Kikuta, Terumasa Komuro

    CELL AND TISSUE RESEARCH   328 ( 2 ) 271 - 279  2007.05

     View Summary

    The distribution and ultrastructure of the interstitial cells of Cajal (ICC) has been examined in the small intestine of the frog Xenopus laevis, as the physiological significance of these cells remains obscure in amphibians and other lower vertebrates. The present study has revealed the existence of a special type of interstitial cell in the tunica muscularis of the small intestine of Xenopus; this cell is characterized by the presence of numerous caveolae, many small mitochondria, and the formation of intercellular connections with the same type of cell. Since these ultrastructural features are shared with mammalian ICC, the cells in the small intestine of Xenopus probably correspond to ICC. These cells also form close contacts with neighboring smooth muscle cells and with nerve varicosities containing accumulations of synaptic vesicles. These cellular networks are likely to be involved in the transmission of nerve impulses to muscle cells, as has been suggested for mammalian tissues. However, true gap junctions have not been detected; they occur neither between the same type of cells nor between the putative ICC and smooth muscle cells. The widespread distribution of ICC or equivalent cells in different groups of vertebrates, together with the conservation of their ultrastructural features, suggests that they differentiated early in vertebrate evolution to play key regulatory roles in gastrointestinal movement.

    DOI

  • Ultrastructural observations of the tunica muscularis in the small intestine of Xenopus laevis, with special reference to the interstitial cells of Cajal

    Sachiko Miyamoto-Kikuta, Terumasa Komuro

    CELL AND TISSUE RESEARCH   328 ( 2 ) 271 - 279  2007.05

     View Summary

    The distribution and ultrastructure of the interstitial cells of Cajal (ICC) has been examined in the small intestine of the frog Xenopus laevis, as the physiological significance of these cells remains obscure in amphibians and other lower vertebrates. The present study has revealed the existence of a special type of interstitial cell in the tunica muscularis of the small intestine of Xenopus; this cell is characterized by the presence of numerous caveolae, many small mitochondria, and the formation of intercellular connections with the same type of cell. Since these ultrastructural features are shared with mammalian ICC, the cells in the small intestine of Xenopus probably correspond to ICC. These cells also form close contacts with neighboring smooth muscle cells and with nerve varicosities containing accumulations of synaptic vesicles. These cellular networks are likely to be involved in the transmission of nerve impulses to muscle cells, as has been suggested for mammalian tissues. However, true gap junctions have not been detected; they occur neither between the same type of cells nor between the putative ICC and smooth muscle cells. The widespread distribution of ICC or equivalent cells in different groups of vertebrates, together with the conservation of their ultrastructural features, suggests that they differentiated early in vertebrate evolution to play key regulatory roles in gastrointestinal movement.

    DOI

  • Structure and organization of interstitial cells of Cajal in the gastrointestinal tract

    Terurnasa Komuro

    JOURNAL OF PHYSIOLOGY-LONDON   576 ( 3 ) 653 - 658  2006.11

     View Summary

    The morphological features of interstitial cells of Cajal (ICC) in the gastrointestinal (GI) tract are described based on observations of laboratory animals including mice, rats and guinea-pigs, using immunohistochemical staining for Kit and electron microscopy. ICC show a specific distribution, arrangement and cell shape depending on their location within various regions and tissue layers of the GI tract. Hence they are classified into several subtypes. The stomach shows distinct regional variations in the distribution of subtypes of ICC from the cardia to pylorus, whereas the small intestine and colon both seem to retain nearly the same distribution pattern of subtypes of ICC throughout each organ. All subtypes of ICC share common ultrastructural features, such as the presence of numerous mitochondria, abundant intermediate filaments, and formation of gap junctions with the same type of cells and with smooth muscle cells. In addition, depending on their species and anatomical location, some subtypes of ICC show some features typical of smooth muscle cells including a basal lamina, caveolae, subsurface cisterns and dense bodies. ICC are somewhat heterogeneous morphologically. A question is raised on a special relationship between their ultrastructural features and dependency on Kit/stem cell factor system. As the neuromediator function of ICC, reciprocal distribution of ICC and gap junctions in the muscle coat is demonstrated by the comparison of Kit immunoreactive cells and gap junction protein connexin 43 in both small intestine and colon.

    DOI

  • Structure and oraganization of interstitial cells of Cajal in the gastrointestinal tract.

    T. Komuro

    J Physiol   ( 576 ) 653 - 658  2006

    DOI

  • Intercellular coupling of interstitial cells of Cajal in the digestive tract

    Hanani M, Farrugia G, Komuro T

    International Review of Cytology   242:249-282  2005

    DOI

  • Intercellular coupling of interstitial cells of Cajal in the digestive tract

    Hanani M, Farrugia G, Komuro T

    International Review of Cytology   242:249-282  2005

    DOI

  • Characterization of in vitro gutlike organ formed from mouse embryonic stem cells

    T Ishikawa, S Nakayama, T Nakagawa, K Horiguchi, H Misawa, M Kadowaki, A Nakao, S Inoue, T Komuro, M Takaki

    AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY   286 ( 6 ) C1344 - C1352  2004.06

     View Summary

    Using an embryoid body (EB) culture system, we have made a functional organlike cluster: the "gut" from embryonic stem (ES) cells (ES gut). There are many types of ES clusters, because ES cells have a pluripotent ability to develop into a wide range of cell types. Before inducing specific differentiation by exogenously added factors, we characterized comprehensive physiological and morphological properties of ES guts. Each ES gut has a hemispherical (or cystic) structure and exhibits spontaneous contractions [mean frequency: 13.5 +/- 8.8 cycles per min (cpm)]. A dense distribution of interstitial cells of Cajal (ICC) was identified by c-Kit immunoreactivity, and specific subcellular structures of ICC and smooth muscle cells were identified with electron microscopy. ICC frequently formed close contacts with the neighboring smooth muscle cells and occasionally formed gap junctions with other ICC. Widely propagating intracellular Ca2+ concentration oscillations were generated in the ES gut from the aggregates of c-Kit immunopositive cells. Plateau potentials, possibly pacemaker potentials in ICC, and electrical slow waves were recorded for the first time. These events were nifedipine insensitive, as in the mouse gut. Our present results indicate that the rhythmic pacemaker activity generated in ICC efficiently spreads to smooth muscle cells and drives spontaneous rhythmic contractions of the ES gut. The present characterization of physiological and morphological properties of ES gut paves the way for making appropriate models to investigate the origin of rhythmicity in the gut.

    DOI

  • Characterization of in vitro gutlike organ formed from mouse embryonic stem cells

    T Ishikawa, S Nakayama, T Nakagawa, K Horiguchi, H Misawa, M Kadowaki, A Nakao, S Inoue, T Komuro, M Takaki

    AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY   286 ( 6 ) C1344 - C1352  2004.06

     View Summary

    Using an embryoid body (EB) culture system, we have made a functional organlike cluster: the "gut" from embryonic stem (ES) cells (ES gut). There are many types of ES clusters, because ES cells have a pluripotent ability to develop into a wide range of cell types. Before inducing specific differentiation by exogenously added factors, we characterized comprehensive physiological and morphological properties of ES guts. Each ES gut has a hemispherical (or cystic) structure and exhibits spontaneous contractions [mean frequency: 13.5 +/- 8.8 cycles per min (cpm)]. A dense distribution of interstitial cells of Cajal (ICC) was identified by c-Kit immunoreactivity, and specific subcellular structures of ICC and smooth muscle cells were identified with electron microscopy. ICC frequently formed close contacts with the neighboring smooth muscle cells and occasionally formed gap junctions with other ICC. Widely propagating intracellular Ca2+ concentration oscillations were generated in the ES gut from the aggregates of c-Kit immunopositive cells. Plateau potentials, possibly pacemaker potentials in ICC, and electrical slow waves were recorded for the first time. These events were nifedipine insensitive, as in the mouse gut. Our present results indicate that the rhythmic pacemaker activity generated in ICC efficiently spreads to smooth muscle cells and drives spontaneous rhythmic contractions of the ES gut. The present characterization of physiological and morphological properties of ES gut paves the way for making appropriate models to investigate the origin of rhythmicity in the gut.

    DOI

  • Morphological features of ICC

    Komuro T

    Gann Monograph on Cancer Research., 53 “Gastrointestinal Stromal Tumor (GIST): From Pathology to Molecular Target Therapy”   113-134  2004

  • Morphological features of ICC

    Komuro T

    Gann Monograph on Cancer Research., 53 “Gastrointestinal Stromal Tumor (GIST): From Pathology to Molecular Target Therapy”   113-134  2004

  • Distribution and ultrastructure of interstitial cells of Cajal in the gastric antrum of wild-type and Ws/Ws rats.

    Mitsui R, Komuro T

    Anat Embryol   206:453-460  2003

  • Distribution and ultrastructure of interstitial cells of Cajal in the gastric antrum of wild-type and Ws/Ws rats.

    Mitsui R, Komuro T

    Anat Embryol   206:453-460  2003

  • Distribution of interstitial cells of Cajal and gap junction protein, Cx 43 in the stomach of wild-type and W/W-v mutant mice

    K Seki, T Komuro

    ANATOMY AND EMBRYOLOGY   206 ( 1-2 ) 57 - 65  2002.12

     View Summary

    The distribution of different subtypes of interstitial cells of Cajal (ICC) in the tunica muscularis of the stomach of wild-type and W/W-v mice was studied by immunohistochemical staining for Kit. Special attention was also given to the distribution of the gap junction protein connexin 43 (Cx 43) immunoreactivity. Kit-immunoreactive cells of the circular and longitudinal muscle layers (ICC-CM and ICC-LM) were densely distributed throughout the cardia, fundus, the squamous epithelial portion of the corpus and the pylorus, but they were decreased in number within the glandular epithelial portion of the corpus. Kit-immunoreactive cells of the myenteric region (ICC-AP) emerged slightly proximal to the squamous-glandular epithelia] transition and increased in number towards the pylorus. Kit-positive cells were also observed at the submucosal border of the circular muscle layer (ICC-SM). ICC-CM and ICC-LM were not observed in the stomachs of W/W-v mice, but a few ICC-AP were observed in the pylorus. Cx 43 immunoreactive deposits were only sparsely distributed in the circular muscle layers of the cardia, fundus and the squamous epithelial portion of corpus. However, the Cx 43 immunoreactive deposits were densely distributed in the glandular epithelial portion of the corpus that contained fewer ICC-CM. Cx 43 immunoreactive deposits were rare in the circular muscle layer of the pylorus. No Cx 43 immunoreactivity was detected in the longitudinal muscle layer throughout the whole stomach. The distribution of Cx 43 immunoreactivity in the W/W-v mouse stomach was almost the same as in wild-type mice. The functional significance of each type of ICC at each region is discussed in reference to regional differences in the distribution of both ICC and Cx 43, and differences between wild-type and W/W-v mice.

    DOI

  • Distribution of interstitial cells of Cajal and gap junction protein, Cx 43 in the stomach of wild-type and W/W-v mutant mice

    K Seki, T Komuro

    ANATOMY AND EMBRYOLOGY   206 ( 1-2 ) 57 - 65  2002.12

     View Summary

    The distribution of different subtypes of interstitial cells of Cajal (ICC) in the tunica muscularis of the stomach of wild-type and W/W-v mice was studied by immunohistochemical staining for Kit. Special attention was also given to the distribution of the gap junction protein connexin 43 (Cx 43) immunoreactivity. Kit-immunoreactive cells of the circular and longitudinal muscle layers (ICC-CM and ICC-LM) were densely distributed throughout the cardia, fundus, the squamous epithelial portion of the corpus and the pylorus, but they were decreased in number within the glandular epithelial portion of the corpus. Kit-immunoreactive cells of the myenteric region (ICC-AP) emerged slightly proximal to the squamous-glandular epithelia] transition and increased in number towards the pylorus. Kit-positive cells were also observed at the submucosal border of the circular muscle layer (ICC-SM). ICC-CM and ICC-LM were not observed in the stomachs of W/W-v mice, but a few ICC-AP were observed in the pylorus. Cx 43 immunoreactive deposits were only sparsely distributed in the circular muscle layers of the cardia, fundus and the squamous epithelial portion of corpus. However, the Cx 43 immunoreactive deposits were densely distributed in the glandular epithelial portion of the corpus that contained fewer ICC-CM. Cx 43 immunoreactive deposits were rare in the circular muscle layer of the pylorus. No Cx 43 immunoreactivity was detected in the longitudinal muscle layer throughout the whole stomach. The distribution of Cx 43 immunoreactivity in the W/W-v mouse stomach was almost the same as in wild-type mice. The functional significance of each type of ICC at each region is discussed in reference to regional differences in the distribution of both ICC and Cx 43, and differences between wild-type and W/W-v mice.

    DOI

  • Direct and indirect innervation of smooth muscle cells of rat stomach, with special reference to the interstitial cells of Cajal

    R Mitsui, T Komuro

    CELL AND TISSUE RESEARCH   309 ( 2 ) 219 - 227  2002.08

     View Summary

    Interstitial cells of Cajal in the circular (ICCCM) and longitudinal (ICC-LM) muscle layer of the rat gastric antrum and their innervation were studied ultrastructurally. Both ICC-CM and ICC-LM are characterized by many mitochondria, rough and smooth endoplasmic reticulum, caveolae, and formation of gap junctions with each other and with muscle cells, though ICC-LM tend to show more variable cytoplasmic features depending on section profiles. Close contacts between nerve terminals and both ICC-CM and ICC-LM are observed. These possible synaptic structures are characterized by: (1) accumulation of synaptic vesicles in nerve varicosities, (2) a narrow gap (about 20 nm) between pre- and postjunctional membranes, (3) lack of a basal lamina between pre- and postjunctional membranes, and (4) the presence of an electron-dense lining on the inner aspect of prejunctional membranes. Almost the same characteristics are observed between the nerve terminals and the muscle cells of both circular and longitudinal muscle layers of the same specimens. Therefore, we conclude that the smooth muscle cells of both circular and longitudinal layers of the rat antrum are directly and indirectly innervated via ICC. Their functional significance is discussed.

    DOI

  • Direct and indirect innervation of smooth muscle cell of rat stomach, with special reference to interstitial cells of Cajal.

    Mitsui R, Komuro T

    Cell Tissue Res.   309:219-227  2002

    DOI

  • Immunohistochemical demonstration of the gap junction proteins connexin

    Seki K, Komuro T

    Cell Tissue Res.   306:417-442  2001

  • Immunohistochemical demonstration of the gap junction proteins connexin

    Seki K, Komuro T

    Cell Tissue Res.   306:417-442  2001

  • Ultrastructural observations of fibroblast-like cells forming gap junctions in the W/Wvmouse small intestine.

    Horiguchi K, Komuro T

    J.Auton.Nerv.Syst.   80:142-147  2000

    DOI

  • Properties of gastric smooth muscles obtained from mice which lack inositol triphosphate receptors

    Suzuki H, Yamamoto Y, Komuro T, Saito M, Kato K, Mikoshiba K

    J Physiol.(Lond)   525:105-111  2000

  • Ultrastructural observations of fibroblast-like cells forming gap junctions in the W/Wvmouse small intestine.

    Horiguchi K, Komuro T

    J.Auton.Nerv.Syst.   80:142-147  2000

    DOI

  • Properties of gastric smooth muscles obtained from mice which lack inositol triphosphate receptors

    Suzuki H, Yamamoto Y, Komuro T, Saito M, Kato K, Mikoshiba K

    J Physiol.(Lond)   525:105-111  2000

  • Comparative morphology of interstitial cells of Cajal: Ultrastructural characterization

    Terumasa Komuro

    Microscopy Research and Technique   47 ( 4 ) 267 - 285  1999.11

     View Summary

    The shape, distribution, and ultrastructural features of interstitial cells of Cajal (ICC) of different tissue layers and organs of the rat and guinea-pig digestive tract were described and compared with the corresponding cells in other species including mice, dogs, and humans, as reported in the literature. By light microscopy, the best marker for ICC appeared to be immunoreactivity for c-Kit. Ultrastructurally, ICC were characterized by the presence of many mitochondria, bundles of intermediate filaments, and gap junctions, which linked ICC with each other. However, ICC were morphologically heterogeneous and had particular features, depending on their tissue and organ location and species. ICC in the deep muscular plexus of the small intestine and in the submuscular plexus of the colon were the most like smooth muscle cells, and had a distinct basal lamina and numerous caveolae. In contrast, ICC of Auerbach's plexus at all levels of the gastrointestinal tract were the least like smooth muscle cells. They most closely resembled unremarkable fibroblasts. ICC within the circular muscle layer were intermediate in form. In addition to the tissue specificity, some organ and species specificity could be distinguished. The structural differences between ICC may be determined by their microenvironment, including the effects of mechanical force, type of nerve supply, and spacial relationship with smooth muscle cells.

    DOI PubMed

  • Ultratructure of intramural ganglia in the striated muscle portions of the guinea pig oesophagus

    J.Anat   5/,111-120  1999

    DOI

  • Ultrastructural characterization of the interstitial cells of Cajal.

    Arch.Histol.Cytol   5-316  1999

  • Comparative morphology of interstitial cells of Cajal : Ultrastructural characterization.

    Microscop.Res.Tech.   /,267-285  1999

    DOI

  • Ultratructure of intramural ganglia in the striated muscle portions of the guinea pig oesophagus

    J.Anat   5/,111-120  1999

    DOI

  • Ultrastructural characterization of the interstitial cells of Cajal.

    Arch.Histol.Cytol   5-316  1999

  • Ultrastructural characterization of interstitial cells of Cajal in the rat small intestine using control and Ws/Ws mutant rats.

    Cell Tissue Res   3/,277-284  1998

    DOI

  • Immunohistochemical study of the c-kit expressing cells and connexin 43 in the guinea-pig digestive tract.

    J. Auton. Nerv. Syst.   /,182-187  1998

    DOI

  • Further observation of the gap junction-rich cells in the deep muscular plexus of the rat small intestine.

    Anat. Embryol.   7/,97-111  1998

  • Distribution of myenteric NO neurons along the guinea pig esophagus.

    J. Auton. Nerv. Syst.   /,91-99  1998

    DOI

  • Ultrastructural characterization of interstitial cells of Cajal in the rat small intestine using control and Ws/Ws mutant rats.

    Cell Tissue Res   3/,277-284  1998

    DOI

  • Immunohistochemical study of the c-kit expressing cells and connexin 43 in the guinea-pig digestive tract.

    J. Auton. Nerv. Syst.   /,182-187  1998

    DOI

  • Further observation of the gap junction-rich cells in the deep muscular plexus of the rat small intestine.

    Anat. Embryol.   7/,97-111  1998

  • Distribution of myenteric NO neurons along the guinea pig esophagus.

    J. Auton. Nerv. Syst.   /,91-99  1998

    DOI

  • Ultrastructural identification of the c-kit-expressing interstitial

    Cell Tissue Research   9/,137-143  1997

  • Ultrastructural identification of the c-kit-expressing interstitial

    Cell Tissue Research   9/,137-143  1997

  • Identification of the interstitial cells of Cajal.

    Histology and Histopathology   /,769-786  1996

  • Characterization of the interstitial cells associated with the submuscular plexus of the guinea-pig colon.

    Anatory and Enbryology   4/,49-55  1996

  • Anti-c-kit protein immunoreactive cells corresponding to the interstitial cells of Cajal in the guinea-pig small intestine.

    J. Autonomic Nervous System   /,169-174  1996

    DOI

  • Identification of the interstitial cells of Cajal.

    Histology and Histopathology   /,769-786  1996

  • Characterization of the interstitial cells associated with the submuscular plexus of the guinea-pig colon.

    Anatory and Enbryology   4/,49-55  1996

  • Anti-c-kit protein immunoreactive cells corresponding to the interstitial cells of Cajal in the guinea-pig small intestine.

    J. Autonomic Nervous System   /,169-174  1996

    DOI

  • Ultrastructure of the zinc iodide-osmic acid stained cells in guinea pig small intestine.

    J. Anat.   7/,481-485  1995

  • Fine structural study of interstitial cells associated with the deep

    Cell Tissue Res.   2/,129-134  1995

  • Ultrastructure of the zinc iodide-osmic acid stained cells in guinea pig small intestine.

    J. Anat.   7/,481-485  1995

  • Fine structural study of interstitial cells associated with the deep

    Cell Tissue Res.   2/,129-134  1995

  • Application of a new morphometry system based on SEM stereo-pairs to the study of intestinal mucosa of rodents.

    J. Eletron Microsc.   /,72-76  1994

  • Application of a new morphometry system based on SEM stereo-pairs to the study of intestinal mucosa of rodents.

    J. Eletron Microsc.   /,72-76  1994

  • The cellular network of interstitial cells associated with the deep muscular plexus of the guinea pig small intestine.

    Anat. Embryol.   6/,519-527  1992

  • Interstitiai cells associated with the deep muscular plexus of the

    Cells Tissue Res.   8/,205-216  1992

  • The cellular network of interstitial cells associated with the deep muscular plexus of the guinea pig small intestine.

    Anat. Embryol.   6/,519-527  1992

  • Interstitiai cells associated with the deep muscular plexus of the

    Cells Tissue Res.   8/,205-216  1992

  • Three-dimensional structure of the rat intestinal wall. (Mucosa and submucosa)

    Arch. Histol. Cytol    1990

    DOI

  • Re-evaluation of fibroblasts and fibroblast-like cells.

    Anatomy and Embryology   2  1990

  • Three-dimensional structure of the rat intestinal wall. (Mucosa and submucosa)

    Arch. Histol. Cytol    1990

    DOI

  • Re-evaluation of fibroblasts and fibroblast-like cells.

    Anatomy and Embryology   2  1990

  • Three-dimensional observation of the fibroblast-like cells associated

    Cell Tissue Res.   5  1989

  • Three-dimensional observation of the fibroblast-like cells associated

    Cell Tissue Res.   5  1989

  • The lattice arrangement of the Collagen fibers in the submucosa of the rat small intestine : scanning electron microscopy.

    Cell Tissue Res.   1  1988

  • Close relationships between the Cells of the immune system and the epithelial cells in the rat small intestine.

    Cell Tissue Res.   4  1988

  • The lattice arrangement of the Collagen fibers in the submucosa of the rat small intestine : scanning electron microscopy.

    Cell Tissue Res.   1  1988

  • Close relationships between the Cells of the immune system and the epithelial cells in the rat small intestine.

    Cell Tissue Res.   4  1988

  • Fenestration of the basal lamina of intestinal villi of the rat : Scanning and transmission electron microscopy.

    Cell Tissue Res   9  1985

    DOI

  • Fenestration of the basal lamina of intestinal villi of the rat : Scanning and transmission electron microscopy.

    Cell Tissue Res   9  1985

    DOI

  • Three-dimensional organization of smmoth muscle cells in blood vessels of laboratory rodents

    Cell Tissue Res.   7  1982

    DOI

  • An Ultrastructural study of neurons and non-neuronal cells in the myenteric plexus of the rabbit colon

    Neuroscience    1982

  • Three-dimensional organization of smmoth muscle cells in blood vessels of laboratory rodents

    Cell Tissue Res.   7  1982

    DOI

  • An Ultrastructural study of neurons and non-neuronal cells in the myenteric plexus of the rabbit colon

    Neuroscience    1982

  • Fine structural study of the abdominal muscle receptor organs of the

    J. Neurocytol.    1981

  • Fine structural study of the abdominal muscle receptor organs of the

    J. Neurocytol.    1981

  • The fine structure of muscle cells and their relationship to connective tissue in the rabbit portal vien.

    Cell Tissue Res.    1980

  • The fine structure of muscle cells and their relationship to connective tissue in the rabbit portal vien.

    Cell Tissue Res.    1980

▼display all

Research Projects

  • 消化管運動調節機構の微細構造

  • 間葉系細胞の多能性

  • 自律神経系末梢部の支配機構

  • 消化管運動調節機構の形態学的解析

  • Multipotency of the mesenchymal cells

  • Morphological analysis of the regulatory system of the gastrointestinal motility

▼display all

Specific Research

  • カハールの介在細胞と類似細胞の形態学的解析

    2009  

     View Summary

     カハールの介在細胞(interstitial cells of Cajal:ICC)は消化管運動のペースメーカーあるいは神経信号の伝達役として広く知られるようになったが、ICC を識別、同定しようとする研究の過程で、異種類似細胞の平滑筋運動への関与も示唆されるようになり、 (1)消化管運動調節機構を包括的に考察する上では、神経、筋、ICC に加えICC 類似細胞も含めた細胞要素の相互の関係を三次元的に捉えることが重要となって来ている。また、(2)ICC 自体についても、各サブタイプの個々の細胞学的特徴にとどまらず、ネットワークとしての広がり、相互の連続性の有無などの検索が、調節機能の考察に必要となって来ている。 ところで、ICC の同定にはc-Kit 受容体蛋白の免疫組織化学が特異的染色法として用いられているが、Kit 陰性ICC類似細胞の描出には、信頼性の高い確実な手法は無く、本研究においても、種々模索する段階にあった。しかしながら、本年、競合する研究者によりPDGFR (platelet-deribed growth factor receptor) の免疫染色を用いたマウス消化管でのKit 陰性ICC類似細胞が観察され、ICC とは異なる細胞性ネットワークの存在することが証明された。これに則り、成果の総合的検討の必要上、手元データとしてICC 観察の蓄積のあるモルモットでの同手法を試みたが、動物種差によるものかモルモットでの描出は困難であった。 そこで、以後、(2)の観点からの課題に絞り、モルモット結腸における ICC の立体的構築について検索した。 その結果、結腸筋叢間神経叢のICC-MPは、これまで報告してきた消化管部位に照らしてみると、胃幽門部とは異なる一方、小腸のICC-MPと同様、神経節周辺に籠状構造を作ることが明らかとなった。また、小腸に比して良く発達した輪走筋層内の ICC-CM は連続したネットワークを構成しており、ICC-MP とも組織層を越えて連絡していることが明らかとなった。

  • 消化管におけるICC類似細胞の形態学的解析

    2008  

     View Summary

     消化管の運動は、交感、副交感の自律神経によって調節されていると、考えられて来たが、近年では、これに加えて、内在性の腸管神経系とカハールの介在細胞(interstitital cells of Cajal:ICC)が制御機構の一員として、重要な役割を担うことが明らかとなっている。ICCは、消化管運動のペースメーカー或は神経からの信号を平滑筋に伝える興奮伝達機能をもつことが証明されているが、ICCの研究が進むなかで、更に、ICCとは細胞学的に異種類似の細胞の存在が判明し、平滑筋運動の包括的理解のための新たな課題となっている。ICCは線維芽細胞に似た特徴を示す間葉系の細胞で、c-kit遺伝子の支配を受けるKit受容体を細胞膜上に持つことから、Kit抗体を用いた免疫染色により陽性細胞として識別される。一方、本研究で注目する類似の細胞はKit染色陰性で、その分布の詳細は、これまでのところ不明である。 そこで、モルモット小腸および大腸を材料として、筋層におけるICC類似細胞の分布や他細胞要素との関係を明らかにすることを目的として、まず、間葉系細胞に特異的にみられるCD34抗体の免疫染色による描出を試みた。凍結切片では、小腸筋層内にCD34陽性細胞の存在は観察できたが、二次元的広がりの中の分布、ネットワークを知るための筋層剥離伸展標本では、充分な観察像は得られなかった。固定の強度など(ザンボニ固定、パラホルムアルデヒド固定、アセトン固定など種類、時間、濃度)を調節し、なお検討を続行している。免疫染色の不調を補うため、電子顕微鏡による微細構造上の検索に重点を移して観察を行い、モルモット小腸筋層に、ICCと異なる特徴を持ち、かつ、線維芽細胞と類似した細胞が、神経終末、平滑筋細胞と接着装置により結合するのを認めた。これらの所見は、平滑筋の運動制御に関与するKit抗体染色陰性のICC類似細胞に相当するものと推定した。

  • カハールの介在細胞各サブタイプの細胞学的特性とキット陰性類似細胞の解析

    2006  

     View Summary

    カハールの介在細胞(Interstitial Cells of Cajal :ICC)は、消化管筋組織における運動のペースメーカーおよび神経信号の伝達装置として働くことが、従来の研究によって明らかにされているが、その分布や形態学的特徴は消化管の部位によって異なる。本研究では、同一の器官内でも領域によってICCサブタイプの分布に相違を示す事が知られている胃について、ICC細胞網の三次元的構築、神経要素との関係等、詳細な解析を進めるためモルモットを材料として検索した。手法としては、Kit抗体(ICC),PGP9.5抗体(神経要素)による免疫組織化学的染色を用い、共焦点顕微鏡によって観察した。 輪走および縦走筋層内のICCは部位により相違を示し、胃底部では単純な双極性の形の細胞が多く、胃体部より幽門部にかけては一次突起の先端で分枝を示すものが多く観察された。分枝の傾向は、輪走筋層の内層(粘膜に近い側)でより多く見られる傾向にあった。筋層内のICCは輪走縦走両筋層とも、神経腺維と密接して観察されたが、これは、ICCの神経信号の伝達装置としての機能と良く符号する所見であった。また、幽門括約筋部に近い幽門前庭部の極く一部には、輪走筋層と粘膜下結合組織との境界部にICC-SMが観察された。 筋層間神経叢部のICC-MPは胃底部には存在せず、胃体部から少数出現し、幽門前庭部では非常に発達して認められた。全載伸展標本による観察から、この幽門前庭部のICC-MPは小腸で見られるような神経節を囲む明瞭な籠状構造は作らず、不規則な束状、集塊状をなして分布することが明らかとなった。胃では蠕動運動は胃体部から始まり幽門部に伝播することが生理学的実験から知られているが、これらの生理学的知見との関連のもとに上記の観察所見について考察した。

  • 消化管運動調節に与る間質性細胞の細胞組織学的研究

    2004  

     View Summary

     間葉系由来のカハールの介在細胞(Interstitial cells of Cajal: ICC)が消化管蠕動運動のペースメーカーおよび平滑筋への興奮伝達機能を有することは、既に周知の事実となったが、その一方、多年に渡って蓄積されて来た腸管神経系の研究成果、例えば、各種ニューロンの支配領域、投射方向などを示す回路図に対応させ、どのように運動制御機構に関わっているのかを具体的に検討するまでの充分な成果は得られていない。 本研究では、このような考察のための基本的データを得るため、モルモットの小腸を材料として、ICC各型の三次元的構築、数量的特徴について検索を試みた。試料は全載伸展標本としてICCの描出にはc-Kit抗体、 神経要素にはPGP9.5抗体による免疫組織化学染色を施し、共焦点顕微鏡により観察した。 生後6週令、腸管の円周約20mmの動物の空腸では、筋層間神経節は小腸の長軸に対して、およそ700~800ミクロンの間隔で配列しており、筋層間神経叢のICC-APは個々の神経節をカゴ状に取り巻いているのが明瞭に観察された。多極性の細胞の突起間の距離はしばしば200μmを越え、円周に沿った長さは平均約150μmで、円周あたりの数は約130個であった。 このことは、蠕動運動が腸管の長軸上の一点を通る腸壁の円周から起ると考えるとき、少なくとも約130個のICC-APが同時に発火する可能性を示唆するものである。深部筋神経叢のICC-DMPは同じく多極性の細胞であるが、突起は輪走筋に沿って走行するため、円周方向の突起の長さは約200~300μm、円周あたりの数は約80個、腸管長軸方向の細胞列の間隙は平均50μmであった。また輪走筋層内のICC-CMは輪走方向に平行に位置する長さ約250~350μmの双極性の細胞で、非常にまばらに観察された。

  • カハールの介在細胞の系統発生学的考察

    2004  

     View Summary

     ヒトを含むほ乳類消化管における蠕動運動のペースメーカーとして、カハールの介在細胞(Interstitial cells of Cajal: ICC)の独立した細胞型としての存在が確立されたが、この細胞の進化学的、系統発生学的位置付けを知る成績は皆無にちかい。そこで本研究では、ICC が脊椎動物中どのような動物群に認められるのか、免疫組織化学的ならびに電子顕微鏡的に検索した。 最初に広く検索することが可能なKit 受容体蛋白の抗体を用いた免疫組織化学染色による観察では、カナヘビ(は虫類)、ウシガエル、アフリカツメガエル(両生類)の消化管とも、ICCの細胞網と認められる構造は観察されなかった。しかし、は虫類、両生類のICCとほ乳類によって得られたKit 受容体抗体との適合性の問題、また Kit は発現しないがICCに相当する細胞がある可能性もあるため、次に、電子顕微鏡観察による、微細構造上の判断基準による検討を試みた。 その結果、アフリカツメガエルの小腸では、筋層間神経叢の位置に相当して、神経節細胞、神経膠細胞、線維芽細胞のいずれにも該当しない細胞が神経節細胞の周辺に観察された。この細胞は細胞質の電子密度が低く、豊富なミトコンドリアを含み、表面細胞膜にはカベオラが認められた。また、発達した細胞突起は互いにギャップ結合で結合し、細胞網を構成するのが観察された。これらの特徴は、マウスやラット等ほ乳類の実験動物で知られているICCの微細構造上の判断基準に合致するものであり、従来広く使用されているKit抗体(ACK2)による免疫組織化学では検出されないものの、アフリカツメガエル小腸筋層間神経叢部にはICCが存在するものと推定した。

  • 消化管運動調節に与るカハールの介在細胞の細胞組織学的研究

    2002  

     View Summary

     蠕動運動のペースメーカーや神経筋興奮伝達の介在機能をもつカハールの介在細胞(ICC)は、消化管の部位に固有な運動を制御していることが推定され、その解析は消化管平滑筋運動の理解の上での重要な課題である。本研究では、胃の各領域、組織層におけるICCの分布を明らかにすると共に、ICC各亜型の細胞学的特性を知るため、マウスおよびラットの胃を材料に用い、免疫組織化学的ならびに電子顕微鏡的に検索した。 正常マウス胃の噴門、胃底、胃体重層扁平上皮部の良く発達した輪走および縦走筋層には多くのc-KIT陽性反応、即ち、ICCが観察されたが、筋層間神経叢には認められなかった。筋層間神経叢のICCは胃体腺上皮部への移行部より出現し始め、幽門部には非常に密度高く観察された。一方、gap junction 蛋白Cx43は、噴門、胃底、胃体重層扁平上皮部、幽門部を通じて、輪層筋層に散在性に弱く観察されたが、胃体腺上皮部では、高い密度で観察された。 これらの観察より、マウス胃では、ペースメーカー機能をもつ筋層間神経叢のICCが出現する胃体腺上皮が自律的蠕動運動の起始部にあたると推定された。また、噴門、胃底、胃体重層扁平上皮部、幽門部の輪走筋層の細胞間の電気的結合度は弱く、豊富なICCが神経信号の伝達に介在するものと推定された。他方、c-kitに 突然変異のあるW/Wvマウスでは、胃の全領域を通じて筋層内のICCは欠損する傍ら、幽門部の筋層間神経叢のICCは少数観察され、ICCの亜型によってc-kit/SCF 系に対する依存性に相違のあることが明らかとなった。 ラット胃を材料とした幽門部筋層の検索では、これまでに報告の無い縦走筋層内のICC に焦点を当て検索した。縦走筋内のICCは豊富なミトコンドリア、中間径フィラメント、カヴェオラを含み、同種細胞間、平滑筋とgap junctions を形成する点で、これまで報告されてきた輪走筋内のICC と共通する特徴もつことが示され、シナップス小胞を多量に含む神経終末と密接して観察された。他方、神経終末は平滑筋とも直接密接する像が観察されたことより、ラット胃幽門部の縦走筋は、ICCを介する間接支配と神経による直接支配との平行支配を受けるものと推定された。

  • 消化管運動調節機構に与る非神経非筋細胞の細胞組織学的研究

    2000  

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     本研究では、消化管筋層に存在するカハールの介在細胞(ICC)の刺激伝達装置としての機能を解析すると共に、各器官組織層に分布するICCの細胞組織学的分類を行い総括した。* ラット小腸深部筋神経叢の免疫組織化学的検索では、豊富な神経支配を受けている深部筋神経層のICC(ICC-DMP)はCx43抗体に陽性なgap junctionによって平滑筋と結合しており、gap juncitonを介した細胞網を通じて、刺激伝達機能の役割を担っているものと推定した。* また、消化管のNANC抑制性神経として知られているNOニューロンのICC支配についての検索では、ラット小腸深部筋神経叢に沿ってNADPH-diaphorase組織化学に陽性の強い反応が観察された。同様に処理した標本の電子顕微鏡観察では、ICCに密接してシナップス小胞を含む反応陽性の終末が観察された。また凍結切片によるVIP免疫染色では、深部筋神経叢に一致して強い陽性反応が規則的に観察された。以上の観察から、ICCはNOニューロンの運動支配を受け、筋とのgap junctionを介して刺激を伝達するものと推定した。また同一ニューロンにおけるNOとVIPの混在の可能性についても考察した。* 一方、消化管各部位、各組織層の違いによるICCの細胞学的特性を系統的に整理するため、従来の研究成果を補完する微細構造学的検索を行った。その結果、ラットおよびモルモットでは、胃、小腸、結腸を通して、筋層間神経叢部に線維芽細胞に類似したICC-APが認められたが、小腸深部筋神経叢部のICC-DMPと結腸筋層下神経叢部のICC-SMPにはカヴェオラや明瞭な基底膜が観察され、平滑筋に似た特徴が見られた。また、胃および結腸輪走筋層内のICC-CMでは、連続した基底膜は欠くもののカヴェオラは観察されるなど、両者の中間的な特徴が見られた。ICC-DMP,ICC-SMPは勿論、胃、結腸のICC-CMにおいても、平滑筋とgap junctionを形成し、神経終末と密接することから、神経信号のmediatorとして働くものと推定した。

  • 食道筋層間神経叢の微細構造

    1998  

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     消化管に内在し、蠕動運動の調節を行う筋層間神経叢は食道横紋筋部にも存在するが、この部位では迷走神経の直接支配を受けることが定説となっており、内在性神経叢の構造と機能については不明な点を多く残してきた。本研究では、食道筋層のほぼ全長にわたって横紋筋線維をもつモルモット食道を材料に用い、食道横紋筋部筋層間神経叢の微細構造を明らかにすることを目的として、電子顕微鏡的に検索を行った。 その結果、モルモット食道筋層間神経節は神経筋細胞、神経膠細胞およびそれらの突起が複雑に絡み合った緻密な神経網を形成し、中枢神経系組織に類似した特徴をそなえている一方、細部については食道固有の構造を持つことが明らかとなった。神経節への知覚性および介在性ニューロン入力の少ないことを示す神経終末の数や種類に乏しいこと、神経要素の疎な神経節の形状を整え機械的衝撃を緩衝すると推測される神経膠細胞の特異な層板状構造、等が観察された。また、迷走神経起源と考えられる有髄線維が、ミトコンドリアを豊富に含む軸索膨大部との連続性を持って神経節内に観察されたことは、知覚終末を示唆する貴重な観察結果と言える。NADPH-d反応の微細構造レベルの観察においては、多数の神経節細胞に反応が認められる一方、外来性神経束では軸索総数の約3%に反応が見られるのみであることから、この観察所見は、横紋筋支配のNADPH-d反応陽性線維が内在性由来であることを、更に支持するものと推定した。

  • 突然変異ラットによる消化管運動ペースメーカーの細胞学的解析

    1997  

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    本研究では、ペースメーカーとの密接な関係が報告されているc-kit receptorに注目し、消化管運動ペースメーカーとして提唱されているカハールの介在細胞(Interstitial Cells of Cajal; ICC)の細胞学的解析を目的とした。材料としてはc-kit遺伝子に突然変異をもち、消化管運動に異常のあることが知られているWs/Wsラットおよび同腹の正常ラット+/+を用い、消化管各部位におけるc-kit発現細胞の電子顕微鏡的観察による比較、検討を行った。 その結果、(a)筋層間神経叢のICCは、消化管の部位(胃、小腸、大腸)に拘らず、共通の微細構造(豊富なミトコンドリア、大きなgap-junctionの形成など)によって特徴ずけられることを確認した。また、これらの細胞はWs/Wsラットでは観察されなかった。(b)一方、小腸の深部筋神経叢及び大腸の筋層下神経叢のICCでは、上記の特徴に加え、基底膜、caveolaeを示したが、この細胞はWs/Wsラットでも観察された。以上の観察結果から、ICCは細胞学的に不均一な細胞群からなり、c-kitに対する依存度についても異なる細胞型を含むものと推定した。また筋層間神経叢のICCはペースメーカーとして機能するものと考えられるが、その他の部位のICCについては、更に慎重な検索、考察が必要なものと結論した。研究成果の発表1998年Horiguchi K. and Komuro T.Ultrastructural characterization of interstitial cells of Cajal in the rat small intestine using control and Ws/Ws mutant rats. Cell Tissue Res. 293, 277-284.

  • 食道壁内在NOニューロンの細胞組織学的研究

    1996  

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     ヒトを含む動物の食道筋層には、胃、小腸とは異なり横紋筋線維が存在し、骨格筋と同様、神経筋結合部が観察される。従来の定説によれば、これらの横紋筋の神経支配は迷走神経運動核に直接由来するものと考えられてきたが、よく発達した内在性の筋層間神経叢ニューロンの存在理由については疑問のままのこされてきた。ところで、最近の研究によれば、その内在性ニューロンによる筋支配の可能性が示唆されているが、その候補としてNOニューロンが注目されている。NOについては、Non-adrenergic Non-chorinergic(NANC)抑制ニューロンの働きが下部消化管において推定されているが、食道においては、その存在様態についても十分に明らかにされていない。 本研究では、食道の全長にわたるNOニューロンの分布様式、細胞組織学特徴について明らかにする事を目的として、モルモット食道を用い、Nitric oxide synthaseの証明と等価値を持つNADPH(nicotinamide adenine dinucleotide phosphate)-diaphorase活性の検出をする組織化学染色をおこなった。また、上記試料を電子顕微鏡用標本として作製し、微細構造レベルでのNOニューロンについても観察した。 NADPH-d染色陽性細胞(NOニューロン)は、食道全長を通じて多数存在しており、食道上部から下部にわたって変化する筋層間神経叢の構築を反映して分布することが証明された。食道筋層間神経叢は全体として疎で不規則な網目構造を呈するが、上部では神経節策と結合策との境界が不分明なほどNOニューロンは散在するのに対し、下部では神経節策内に限局して密集する。又、運動性と推定されているDogiel1型の細胞も多数みとめられた。電子顕微鏡による観察では、NOニューロンは、細胞質内の粗面小胞体、核膜に NADPH-d陽性反応を示す細胞として観察され、反応陰性の幾つかのタイプの軸策終末のシナップスを受ける一方、神経節内ではシナップス前構造としての明瞭な像を示さない。また筋層内には、内在性と推定される反応陽性の無髄神経線維束が多数認められた。これらの観察をもとに、食道筋層間神経叢のNOニューロンの生理的意義について考察した。

  • 消化管運動ペースメーカー細胞の形態学的解析

    1995  

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    ○研究の背景および目的 固体の生命維持に重要な消化管運動は,自律神経系による調節に加えて,内在するペースメーカーに依って支配されている。従来より,ペースメーカーの存在は,生理学的に知られるところであったが,その細胞学的根拠については不明であった。本研究ではペースメーカーの細胞学的特性および神経,筋要素との組織学的関係を明らかにし,ペースメーカー機能発現の形態学的根拠について検索した。○材料および方法 実験動物としてはモルモットの大腸を用い,標的細胞の微細構造,細胞骨格蛋白の性質を明らかにするため,電子顕微鏡的ならびに免疫組織学的に検索した。また,古典的記載との対照をはかるためヨウカ亜鉛-オスミウム酸(ZIO)法も併用した。○結果および考察 ZIO法にて固定,染色後,大腸の筋層を剥離,伸展標本として観察すると,粘膜下結合組織と輪走筋層との境界部によく発達した神経繊維網が黒染して現われ,これに付随して星形の細胞が認められる。この細胞は,数本の長い突起によって相互に連結し,細胞性の網状構造を作るが,その形状,構成は,消化管運動ペースメーカーとして現在推定されているカハールの介在細胞(Thuneberg, 1982)と酷似する。 同一の標本を電子顕微鏡用試料として再包理し,超薄切片として観察すると,標的細胞はZIOの沈殿物を含む細胞として容易に識別される。この細胞は,よく発達したコルジ装置,小胞体,ミトコンドリアを含み,基底膜は無く微細構造的には繊維芽細胞の特徴を有する。また,間葉系細胞に豊富に存在するビメンチン,フィラメントの抗体で染色するとZIO法にて描出された星形の細胞と同形の細胞が観察される。以上の結果より,モルモット大腸に見られるペースメーカー細胞は,間葉系由来の繊維芽細胞様細胞と推定した。

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