Updated on 2021/12/17

写真a

 
HIRAYAMA Haruko
 
Organization
Advanced Science Research Center Assistant Professor
Position
Assistant Professor
External link

Degree

  • 博士(獣医学) ( 岐阜大学 )

Research Interests

  • 消化管運動

  • 消化管神経系

Research Areas

  • Life Science / Veterinary medical science

  • Life Science / Laboratory animal science

  • Life Science / Physiology

Education

  • Gifu University   連合獣医学研究科博士課程  

    2007.4 - 2011.3

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  • Gifu University   農学部   獣医学科

    1997.4 - 2003.3

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Research History

  • Okayama University   Department of Animal Resources, Advanced Science Research Center   Assistant Professor

    2012.4

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  • University of Melbourne   Department of Anatomy and Cell Biology   Research Assistant

    2012.1 - 2012.3

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  • University of Melbourne   Department of Anatomy and Cell Biology

    2011.6 - 2011.11

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  • Ai Animal Clinic

    2003.4 - 2007.3

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Papers

  • Risk assessment for hepatitis E virus infection from domestic pigs introduced into an experimental animal facility in a medical school Reviewed

    Hirohito Ogawa, Haruko Hirayama, Satsuki Tanaka, Norio Yata, Hikaru Namba, Nobuko Yamashita, Kenzo Yonemitsu, Ken Maeda, Katsumi Mominoki, Masao Yamada

    Journal of Veterinary Medical Science   81 ( 8 )   1191 - 1196   2019

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    Hepatitis E virus (HEV) is known to cause zoonotic infections from pigs, wild boars and deer. Domestic pigs have been used as an experimental animal model in medical research and training; however, the risks of HEV infection from pigs during animal experiments are largely unknown. Here, we retrospectively investigated the seroprevalence and detection rates of viral RNA in 73 domestic pigs (average 34.5 kg) introduced into an animal experimental facility in a medical school during 2012–2016. We detected anti-HEV immunoglobulin G antibodies in 24 of 73 plasma samples (32.9%), though none of the samples were positive for viral RNA. Plasma samples of 18 pigs were sequentially monitored and were classified into four patterns: sustained positive (5 pigs), sustained negative (5 pigs), conversion to positive (6 pigs) and conversion to negative (2 pigs). HEV genomes were detected in 2 of 4 liver samples from pigs that were transported from the same farm during 2016–2017. Two viral sequences of the overlapping open reading frame (ORF) 2/3 region (97 bp) were identical and phylogenetically fell into genotype 3. A 459-bp length of the ORF2 region of an amplified fragment from a pig transported in 2017 was clustered with the wbJYG1 isolate (subgenotype 3b) with 91.5% (420/459 bp) nucleotide identity. Based on our results, we suggest that domestic pigs introduced into animal facilities carry a potential risk of HEV infection to researchers, trainees and facility staff. Continuous surveillance and precautions are important to prevent HEV infection in animal facilities.

    DOI: 10.1292/jvms.19-0086

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  • Sites of action of ghrelin receptor ligands in cardiovascular control Reviewed

    Brid Callaghan, Billie Hunne, Haruko Hirayama, Daniela M. Sartor, Trung V. Nguyen, Fe C. Abogadie, Dorota Ferens, Peter McIntyre, Kung Ban, Jonathan Baell, John B. Furness, James A. Brock

    AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY   303 ( 8 )   H1011 - H1021   2012.10

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:AMER PHYSIOLOGICAL SOC  

    Callaghan B, Hunne B, Hirayama H, Sartor DM, Nguyen TV, Abogadie FC, Ferens D, McIntyre P, Ban K, Baell J, Furness JB, Brock JA. Sites of action of ghrelin receptor ligands in cardiovascular control. Am J Physiol Heart Circ Physiol 303: H1011-H1021, 2012. First published August 10, 2012; doi:10.1152/ajpheart.00418.2012.-Circulating ghrelin reduces blood pressure, but the mechanism for this action is unknown. This study investigated whether ghrelin has direct vasodilator effects mediated through the growth hormone secretagogue receptor 1a (GHSR1a) and whether ghrelin reduces sympathetic nerve activity. Mice expressing enhanced green fluorescent protein under control of the promoter for growth hormone secretagogue receptor (GHSR) and RT-PCR were used to locate sites of receptor expression. Effects of ghrelin and the nonpeptide GHSR1a agonist capromorelin on rat arteries and on transmission in sympathetic ganglia were measured in vitro. In addition, rat blood pressure and sympathetic nerve activity responses to ghrelin were determined in vivo. In reporter mice, expression of GHSR was revealed at sites where it has been previously demonstrated (hypothalamic neurons, renal tubules, sympathetic preganglionic neurons) but not in any artery studied, including mesenteric, cerebral, and coronary arteries. In rat, RT-PCR detected GHSR1a mRNA expression in spinal cord and kidney but not in the aorta or in mesenteric arteries. Moreover, the aorta and mesenteric arteries from rats were not dilated by ghrelin or capromorelin at concentrations >100 times their EC50 determined in cells transfected with human or rat GHSR1a. These agonists did not affect transmission from preganglionic sympathetic neurons that express GHSR1a. Intravenous application of ghrelin lowered blood pressure and decreased splanchnic nerve activity. It is concluded that the blood pressure reduction to ghrelin occurs concomitantly with a decrease in sympathetic nerve activity and is not caused by direct actions on blood vessels or by inhibition of transmission in sympathetic ganglia.

    DOI: 10.1152/ajpheart.00418.2012

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  • Identification of neurons that express ghrelin receptors in autonomic pathways originating from the spinal cord Reviewed

    John B. Furness, Hyun-Jung Cho, Billie Hunne, Haruko Hirayama, Brid P. Callaghan, Alan E. Lomax, James A. Brock

    CELL AND TISSUE RESEARCH   348 ( 3 )   397 - 405   2012.6

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:SPRINGER  

    Functional studies have shown that subsets of autonomic preganglionic neurons respond to ghrelin and ghrelin mimetics and in situ hybridisation has revealed receptor gene expression in the cell bodies of some preganglionic neurons. Our present goal has been to determine which preganglionic neurons express ghrelin receptors by using mice expressing enhanced green fluorescent protein (EGFP) under the control of the promoter for the ghrelin receptor (also called growth hormone secretagogue receptor). The retrograde tracer Fast Blue was injected into target organs of reporter mice under anaesthesia to identify specific functional subsets of postganglionic sympathetic neurons. Cryo-sections were immunohistochemically stained by using anti-EGFP and antibodies to neuronal markers. EGFP was detected in nerve terminal varicosities in all sympathetic chain, prevertebral and pelvic ganglia and in the adrenal medulla. Non-varicose fibres associated with the ganglia were also immunoreactive. No postganglionic cell bodies contained EGFP. In sympathetic chain ganglia, most neurons were surrounded by EGFP-positive terminals. In the stellate ganglion, neurons with choline acetyltransferase immunoreactivity, some being sudomotor neurons, lacked surrounding ghrelin-receptor-expressing terminals, although these terminals were found around other neurons. In the superior cervical ganglion, the ghrelin receptor terminals innervated subgroups of neurons including neuropeptide Y (NPY)-immunoreactive neurons that projected to the anterior chamber of the eye. However, large NPY-negative neurons projecting to the acini of the submaxillary gland were not innervated by EGFP-positive varicosities. In the celiaco-superior mesenteric ganglion, almost all neurons were surrounded by positive terminals but the VIP-immunoreactive terminals of intestinofugal neurons were EGFP-negative. The pelvic ganglia contained groups of neurons without ghrelin receptor terminal innervation and other groups with positive terminals around them. Ghrelin receptors are therefore expressed by subgroups of preganglionic neurons, including those of vasoconstrictor pathways and of pathways controlling gut function, but are absent from some other neurons, including those innervating sweat glands and the secretomotor neurons that supply the submaxillary salivary glands.

    DOI: 10.1007/s00441-012-1405-9

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  • Extract of grains of paradise and its active principle 6-paradol trigger thermogenesis of brown adipose tissue in rats Reviewed

    Momoe Iwami, Fatma A. Mahmoud, Takahiko Shiina, Haruko Hirayama, Takeshi Shima, Jun Sugita, Yasutake Shimizu

    AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL   161 ( 1-2 )   63 - 67   2011.4

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:ELSEVIER SCIENCE BV  

    Grains of paradise (GP) is a species of the ginger family, Zingiberaceae, extracts of which have a pungent, peppery taste due to an aromatic ketone, 6-paradol. The aim of this study was to explore the thermogenic effects of GP extracts and of 6-paradol. Efferent discharges from sympathetic nerves entering the interscapular brown adipose tissue were recorded. Intragastric injection of a GP extract or 6-paradol enhanced the efferent discharges of the sympathetic nerves in a dose-dependent manner. The enhanced nerve discharges were sustained for as long as 3 h. The rats did not become desensitized to the stimulatory effects these compounds on sympathetic nerve activity. The tissue temperature of brown adipose tissue showed significant increase in rats injected with 6-paradol. These results demonstrate that GP extracts and 6-paradol activate thermogenesis in brown adipose tissue, and may open up new avenues for the regulation of weight loss and weight maintenance. (C) 2010 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.autneu.2010.11.012

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  • Intraluminal administration of zingerol, a non-pungent analogue of zingerone, inhibits colonic motility in rats Reviewed

    Momoe Iwami, Takahiko Shiina, Haruko Hirayama, Yasutake Shimizu

    BIOMEDICAL RESEARCH-TOKYO   32 ( 2 )   181 - 185   2011.4

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:BIOMEDICAL RESEARCH PRESS LTD  

    Zingerone, a pungent component of ginger, may exert beneficial therapeutic effects on hypermotility-induced diarrhea because it has the ability to inhibit contractions of colonic smooth muscles. However, the pungency is undesirable for possible therapeutic use. The purpose of this study was to examine effects of zingerol, a non-pungent analogue of zingerone, in rats. Colonic motility in vivo was evaluated by measuring intraluminal pressure changes and expelled fluid volume from the colon in anesthetized rats. Mechanical contractile activities of isolated colonic segments were also recorded. Intracolonic administration of zingerol attenuated colonic motility in vivo without affecting blood pressure and heart rate in a manner similar to that of zingerone. Zingerol also inhibited spontaneous contractile movements in isolated colonic segments, suggesting that zingerol directly acts on the colon. Zingerol had no effect on jejunal motility, although zingerone showed an inhibitory effect to the jejunum. These findings suggest that zingerol can inhibit colonic motility without adverse effects on small intestinal motility and the cardiovascular system. The non-pungent property of zingerol will be useful as an oral or suppository medicine for treating diarrhea and other gastrointestinal disorders.

    DOI: 10.2220/biomedres.32.181

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  • Extract of grains of paradise and its active principle 6-paradol trigger thermogenesis of brown adipose tissue in rats. Reviewed

    Iwami Momoe, Mahmoud Fatma A, Shiina Takahiko, Hirayama Haruko, Shima Takeshi, Sugita Jun, Shimizu Yasutake

    Autonomic neuroscience : basic&clinical   161 ( 1-2 )   63 - 67   2011.4

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    Grains of paradise (GP) is a species of the ginger family, Zingiberaceae, extracts of which have a pungent, peppery taste due to an aromatic ketone, 6-paradol. The aim of this study was to explore the thermogenic effects of GP extracts and of 6-paradol. Efferent discharges from sympathetic nerves entering the interscapular brown adipose tissue were recorded. Intragastric injection of a GP extract or 6-paradol enhanced the efferent discharges of the sympathetic nerves in a dose-dependent manner. The enhanced nerve discharges were sustained for as long as 3h. The rats did not become desensitized to thestimulatory effects these compounds on sympathetic nerve activity. The tissue temperature of brown adipose tissue showed significant increase in rats injected with 6-paradol. These results demonstrate that GP extracts and 6-paradol activate thermogenesis in brown adipose tissue, and may open up new avenues for the regulation of weight loss and weight maintenance.

    DOI: 10.1016/j.autneu.2010.11.012

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  • Inhibitory effects of zingerone, a pungent component of Zingiber officinale Roscoe, on colonic motility in rats Reviewed

    Momoe Iwami, Takahiko Shiina, Haruko Hirayama, Takeshi Shima, Tadashi Takewaki, Yasutake Shimizu

    Journal of Natural Medicines   65 ( 1 )   89 - 94   2011.1

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    Ginger (rhizome of Zingiber officinale Roscoe) is an herbal medicine for the treatment of gastrointestinal disorders including constipation and diarrhea. Zingerone is a likely active constituent responsible for the antidiarrheal activity of ginger. The current study was designed to characterize pharmacological actions of zingerone on colonic motility. To evaluate pharmacological effects of zingerone on colonic motility, we used isolated colonic segments from rats, in which mechanical responses were recorded in the longitudinal direction. In addition, we evaluated the effects on colonic motility in vivo by measuring intraluminal pressure changes and expelled fluid volume from the colon in anesthetized rats. Zingerone was applied to the lumen of the colon to allow the drug to access from the mucosal side. Zingerone inhibited spontaneous contractile movements in the isolated colonic segments in a dose-dependent manner. The inhibitory effects of zingerone on colonic movements were not affected by pretreatment with capsazepine, a typical antagonist of transient receptor potential vanilloid 1. In addition, tetrodotoxin, a blocker of voltage-dependent sodium channels on neurons, did not affect the suppression of colonic movements by zingerone, suggesting that zingerone acts on the smooth muscles directly. Zingerone also attenuated colonic motility in vivo without affecting blood pressure and heart rate. The effects were reversible and reproducible. Our findings suggest that zingerone can inhibit colonic motility via direct action on smooth muscles. Zingerone might exert beneficial therapeutic effects on hypermotility-induced diarrhea by abrogating excessive gastrointestinal motility. © 2010 The Japanese Society of Pharmacognosy and Springer.

    DOI: 10.1007/s11418-010-0463-0

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  • Inhibitory effects of zingerone, a pungent component of Zingiber officinale Roscoe, on colonic motility in rats. Reviewed

    Iwami Momoe, Shiina Takahiko, Hirayama Haruko, Shima Takeshi, Takewaki Tadashi, Shimizu Yasutake

    Journal of natural medicines   65 ( 1 )   89   2011.1

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    Ginger (rhizome of Zingiber officinale Roscoe) is an herbal medicine for the treatment of gastrointestinal disorders including constipation and diarrhea. Zingerone is a likely active constituent responsible for the antidiarrheal activity of ginger. The current study was designed to characterize pharmacological actions of zingerone on colonic motility. To evaluate pharmacological effects of zingerone on colonic motility, we used isolated colonic segments from rats, in which mechanical responses were recorded in the longitudinal direction. In addition, we evaluated the effects on colonic motility in vivo by measuring intraluminal pressure changes and expelled fluid volume from the colon in anesthetized rats. Zingerone was applied to the lumen of the colon to allow the drug to access from the mucosal side. Zingerone inhibited spontaneous contractile movements in the isolated colonic segments in a dose-dependent manner. The inhibitory effects of zingerone on colonic movements were not affected by pretreatment with capsazepine, a typical antagonist of transient receptor potential vanilloid 1. In addition, tetrodotoxin, a blocker of voltage-dependent sodium channels on neurons, did not a

    DOI: 10.1007/s11418-010-0463-0

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  • Contrasting effects of ghrelin and des-acyl ghrelin on the lumbo-sacral defecation center and regulation of colorectal motility in rats. Reviewed

    Hirayama H, Shiina T, Shima T, Kuramoto H, Takewaki T, B Furness J, Shimizu Y

    Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society   22 ( 10 )   1124 - 1131   2010.10

  • Contractile responses induced by physalaemin, an analogue of substance P, in the rat esophagus Reviewed

    Takahiko Shiina, Takeshi Shima, Haruko Hirayama, Hirofumi Kuramoto, Tadashi Takewaki, Yasutake Shimizu

    EUROPEAN JOURNAL OF PHARMACOLOGY   628 ( 1-3 )   202 - 206   2010.2

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    We examined the effects of physalaemin, an agonist of tachykinin receptors, on mechanical responses in the rat esophagus to clarify possible regulatory roles of tachykinins in esophageal motility. Exogenous application of physalaemin caused tonic contractions in rat esophageal segments when tension was recorded in the longitudinal direction but not when tension was recorded in the circular direction. The physalaemin-evoked contractions were blocked by pretreatment with nifedipine, a blocker of L-type calcium channels in both striated and smooth muscle cells. However, tetrodotoxin, a blocker of voltage-dependent sodium channels in striated muscle cells and neurons, did not affect the physalaemin-induced contractions. These results indicate that physalaemin might induce contractile responses in longitudinal smooth muscle of the muscularis mucosa via direct actions on muscle cells but not on neurons. Although pretreatment with a tachykinin NK1 receptor antagonist, N-acetyl-L-tryptophan 3,5-bis (trifluoromethyl) benzyl ester (L-732,138), did not significantly affect the physalaemin-evoked contractions in rat esophageal segments, a tachykinin NK2 receptor antagonist, (S)-N-methyl-N[4-(4-acetylamino-4-phenylpiperidino)-2-(3,4-dichlorophenyl) butyl 1 benzamide (SR48968), and a tachykinin NK3 receptor antagonist, (S)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl) piperidin-3-yl)propyl)-4- phenylpiperidin-4-yl)-N-methylacetamide (SR142801), significantly inhibited the physalaemin-evoked contractions. These results suggest that tachykinins can activate longitudinal contraction of smooth muscle in the muscularis mucosa, mediated via tachykinin NK2 and NK3 receptors on muscle cells, in the rat esophagus. (C) 2009 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.ejphar.2009.11.039

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  • Contractile responses induced by physalaemin, an analogue of substance P, in the rat esophagus. Reviewed

    Shiina Takahiko, Shima Takeshi, Hirayama Haruko, Kuramoto Hirofumi, Takewaki Tadashi, Shimizu Yasutake

    European journal of pharmacology   628 ( 1-3 )   202 - 206   2010.2

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    We examined the effects of physalaemin, an agonist of tachykinin receptors, on mechanical responses in the rat esophagus to clarify possible regulatory roles of tachykinins in esophageal motility. Exogenous application of physalaemin caused tonic contractions in rat esophageal segments when tension was recorded in the longitudinal direction but not when tension was recorded in the circular direction. The physalaemin-evoked contractions were blocked by pretreatment with nifedipine, a blocker of L-type calcium channels in both striated and smooth muscle cells. However, tetrodotoxin, a blocker of voltage-dependent sodium channels in striated muscle cells and neurons, did not affect the physalaemin-induced contractions. These results indicate that physalaemin might induce contractile responses in longitudinal smooth muscle of the muscularis mucosa via direct actions on muscle cells but not on neurons. Although pretreatment with a tachykinin NK(1) receptor antagonist, N-acetyl-l-tryptophan 3,5-bis (trifluoromethyl) benzyl ester (L-732,138), did not significantly affect the physalaemin-evoked contractions in rat esophageal segments, a tachykinin NK(2) receptor antagonist, (S)-N-methyl-N[

    DOI: 10.1016/j.ejphar.2009.11.039

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  • Contractile Properties of Esophageal Striated Muscle: Comparison with Cardiac and Skeletal Muscles in Rats Reviewed

    Takahiko Shiina, Takeshi Shima, Kazuaki Masuda, Haruko Hirayama, Momoe Iwami, Tadashi Takewaki, Hirofumi Kuramoto, Yasutake Shimizu

    JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY   2010   459789   2010

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    The external muscle layer of the mammalian esophagus consists of striated muscles. We investigated the contractile properties of esophageal striated muscle by comparison with those of skeletal and cardiac muscles. Electrical field stimulation with single pulses evoked twitch-like contractile responses in esophageal muscle, similar to those in skeletal muscle in duration and similar to those in cardiac muscle in amplitude. The contractions of esophageal muscle were not affected by an inhibitor of gap junctions. Contractile responses induced by high potassium or caffeine in esophageal muscle were analogous to those in skeletal muscle. High-frequency stimulation induced a transient summation of contractions followed by sustained contractions with amplitudes similar to those of twitch-like contractions, although a large summation was observed in skeletal muscle. The results demonstrate that esophageal muscle has properties similar but not identical to those of skeletal muscle and that some specific properties may be beneficial for esophageal peristalsis.

    DOI: 10.1155/2010/459789

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  • Contractile properties of esophageal striated muscle: comparison with cardiac and skeletal muscles in rats. Reviewed

    Shiina Takahiko, Shima Takeshi, MasudaKazuaki, Hirayama Haruko, Iwami Momoe, Takewaki Tadashi, Kuramoto Hirofumi, Shimizu Yasutake

    Journal of biomedicine&biotechnology   2010   459789   2010

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    The external muscle layer of the mammalian esophagus consists of striated muscles. We investigated the contractile properties of esophageal striated muscle by comparison with those of skeletal and cardiac muscles. Electrical field stimulation with single pulses evoked twitch-like contractile responses in esophageal muscle, similar to those in skeletal muscle in duration and similar to those in cardiac muscle in amplitude. The contractions of esophageal muscle were not affected by an inhibitor of gap junctions. Contractile responses induced by high potassium or caffeine in esophageal muscle were analogous to those in skeletal muscle. High-frequency stimulation induced a transient summation of contractions followed by sustained contractions with amplitudes similar to those of twitch-like contractions, although a large summation was observed in skeletal muscle. The results demonstrate that esophageal muscle has properties similar but not identical to those of skeletal muscle and that some specific properties may be beneficial for esophageal peristalsis.

    DOI: 10.1155/2010/459789

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  • Extract from Calotropis procera latex activates murine macrophages Reviewed

    Abdel Iatif Shaker Seddek, Motamed Elsayed Mahmoud, Takahiko Shiina, Haruko Hirayama, Momoe Iwami, Seiji Miyazawa, Hideki Nikami, Tadashi Takewaki, Yasutake Shimizu

    JOURNAL OF NATURAL MEDICINES   63 ( 3 )   297 - 303   2009.7

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:SPRINGER TOKYO  

    Calotropis procera latex has long been used in traditional medicines. Extracts from C. procera latex have been reported to have various pharmacological actions, including protection from myocardial infarction, hepatoprotective action, antitumor activity, antinociceptive, and pro- and anti-inflammatory actions. To evaluate the immunomodulatory functions of the water-soluble C. procera extract (CPE), we investigated its ability to activate macrophages-effector cells in inflammatory and immune responses. Intraperitoneal injection of CPE in mice (2 mg/mouse) induced migration of macrophages to the intraperitoneal cavity, confirming the proinflammatory effects of water-soluble CPE. The direct effects of CPE on macrophages were then assessed by measuring the production of nitric oxide (NO) as an indicator for macrophage activation. Addition of CPE (1-10 mu g/ml) to the culture medium of the murine monocyte/macrophage cell line RAW264.7 caused an increase in NO production in a time- and dose-dependent manner. CPE-elicited NO production was blocked by application of an inhibitor of inducible nitric oxide synthase (iNOS). Expression of iNOS mRNA was induced by treatment of cultured macrophages with CPE. Injection of CPE in mice also resulted in an increase in plasma NO level. The results suggest that CPE activates macrophages and facilitates NO production via up-regulation of iNOS gene expression.

    DOI: 10.1007/s11418-009-0335-7

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  • Capsaicin pretreatment attenuates LPS-induced hypothermia through TRPV1-independent mechanisms in chicken Reviewed

    Hideki Nikami, Motamed Elsayed Mahmoud, Yasutake Shimizu, Takahiko Shiina, Haruko Hirayama, Momoe Iwami, Reem Mahmoud Dosoky, Moustafa Mohamed Ahmed, Tadashi Takewaki

    LIFE SCIENCES   82 ( 23-24 )   1191 - 1195   2008.6

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:PERGAMON-ELSEVIER SCIENCE LTD  

    it has been demonstrated that chicken TRPV1 (transient receptor potential vanilloid of subtype-1) is insensitive to capsaicin (CAP), and therefore, a chicken model is suitable to analyze the CAP-sensitive TRPV1 independent pathway. We elucidated here the possible involvement of the pathway in hypothermia induced by bacterial endotoxin (lipopolysaccharide, LPS) in chickens. Chicks were pretreated with CAP (10 mg/kg, iv) at 1, 2 and 3 days of age to desensitize them towards the CAP-sensitive pathway. An intravenous injection of LPS in 4-day-old chicks caused progressive hypothermia, ending with collapse and 78% mortality within 12 h after injection. The CAP pretreatment rescued the LPS-induced endotoxin shock and hypothermia in chicks. LPS-induced iNOS expression as well as NO production in liver and lung was suppressed by CAP pretreatment. CAP pretreatment also attenuated hypothermia due to exposure of chicks to cold ambient temperature. These findings suggest that a CAP-sensitive TRPV1-independent pathway may be involved in pathophysiological hypothermic reactions through the mediation of NO in chickens. (c) 2008 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.lfs.2008.04.003

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  • Chicken B lymphoma DT40 cells as a useful tool for in vitro analysis of pathogenic infectious bursal disease virus Reviewed

    Kaori Terasaki, Haruko Hirayama, Christopher J. Kasanga, Min Thein Maw, Kenji Ohya, Tsuyoshi Yamaguchi, Hideto Fukushi

    JOURNAL OF VETERINARY MEDICAL SCIENCE   70 ( 4 )   407 - 410   2008.4

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:JAPAN SOC VET SCI  

    Susceptibility of DT40 cells to pathogenic field strains of infectious bursal disease virus (IBDV) including very virulent and classical virulent strains were studied. After the first and second passage of the virus in DT40 cells, IBDV-specific antigen was readily detected in DT40 cells inoculated with the pathogenic field strain infected bursal homogenates. Nucleotide sequence analysis in the VP2 hypervariable domain, which is critical for the virulence of IBDV, revealed no common amino acid substitutions among the pathogenic IBDVs in accordance with the propagation in DT40 cells. These results indicate that DT40 cells are a useful tool for rapid isolation of pathogenic field strains and successive in vitro analysis of IBDV.

    DOI: 10.1292/jvms.70.407

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  • Fatal necrotic enteritis associated with Clostridium perfringens in wild crows (Corvus macrorhynchos) Reviewed

    Y Asaoka, T Yanai, H Hirayama, Y Une, E Saito, H Sakai, M Goryo, H Fukushi, T Masegi

    AVIAN PATHOLOGY   33 ( 1 )   19 - 24   2004.2

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:CARFAX PUBLISHING  

    Sporadic outbreaks of fatal enteritis occurred among free- living wild crows (` large billed' or ` wok' crow; Corvus macrorhynchos) in an open- air park in Japan in 2002. Eight crows were found dead during February, followed by two more in September, and five of the eight were examined histopathologically. At necropsy, all cases showed a markedly dilated small intestine, especially the jejunum and ileum, with large amounts of gas, and dark red to greenish - brown soft content. The necrotic intestinal wall was markedly thickened with multifocal haemorrhages. All cases had multifocal white foci in the liver, and four cases showed marked splenomegaly. Histologically, there was severe necrotic enteritis characterized by extensive mucosal necrosis and multifocal haemorrhages, as well as inflammatory cell infiltrations. A prominent pseudo- membrane formation was noted in the affected intestine. Severe adhesive peritonitis was also observed in three cases. Gram- positive bacilli were present in large numbers in the lumen, and in and around necrotic lesions in the affected intestine. The bacilli were positive for Clostridium perfringens enterotoxin type A by immunohistochemistry, and were also positive for C. perfringens type A using the immunofluorescence method. C. perfringens was isolated by anaerobic culture from the intestinal contents. The present enteritis was thought to be induced by proliferated C. perfringens in the intestine, and to be the cause of death.

    DOI: 10.1080/03079450310001636228

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  • 実験動物の安楽死の課題 安楽死処置におけるセコバルビタールの有用性

    赤木佐千子, 平山晴子, 樅木勝巳

    Labio 21   ( 81 )   2020

  • 動物実験施設に搬入される家畜ブタにおけるE型肝炎ウイルスの遺伝子検出および血清学的解析

    小川 寛人, 難波 ひかる, 山下 信子, 山田 雅夫, 田中 爽暉, 矢田 範夫, 平山 晴子, 樅木 勝巳, 米満 研三, 前田 健

    臨床とウイルス   46 ( 2 )   S58 - S58   2018.4

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    Language:Japanese   Publisher:日本臨床ウイルス学会  

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  • 【消化器疾患の病態に関わる新たな展開】 グレリンの大腸運動促進作用

    平山 晴子, 樅木 勝巳, 椎名 貴彦, 志水 泰武

    日本薬理学雑誌   143 ( 6 )   270 - 274   2014.6

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    Language:Japanese   Publisher:(公社)日本薬理学会  

    グレリンとは、主に胃から分泌される、28個のアミノ酸からなるペプチドホルモンである。他のホルモンにはないグレリンの特徴として、3番目のセリン残基に脂肪酸による修飾を受けていることが挙げられる。この脂肪酸修飾がグレリン受容体を介した作用発現には必須である。生体内にはグレリンの脂肪酸修飾を持たない型も存在し、デスアシルグレリンと呼ばれるが、脂肪酸修飾を欠くというその構造上、グレリン受容体に対しては不活性型である。しかし近年では、デスアシルグレリンのグレリン受容体以外の経路を介する作用についても多数の報告がなされている。グレリンの作用としては、成長ホルモン分泌促進や、食欲亢進、エネルギー消費の抑制をはじめとし、循環器系への作用、消化器系への作用と、その作用は非常に多岐に渡る。グレリンの消化管運動に対する作用としては、胃や小腸、大腸の運動性を亢進させることなどがこれまでに報告されている。また、消化器疾患におけるグレリンの関与についてもさまざまな知見が報告されており、今後の研究の展開が期待されている。我々はこれまでに、in vivoの実験系を用い、グレリンの脊髄腰仙髄部の排便中枢を介する大腸運動への作用について研究してきた。本稿ではこの結果について、実験系も含め紹介する。(著者抄録)

    DOI: 10.1254/fpj.143.270

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  • ラットにおけるグレリンの大腸運動調節作用

    平山晴子, 樅木勝巳, 椎名貴彦, 志水泰武

    九州実験動物雑誌   29   3 - 7   2013

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  • 脊髄を介するグレリンの大腸運動促進作用

    平山晴子, 樅木勝巳, 椎名貴彦, 志水泰武

    岡山実験動物研究会報   29   51 - 54   2013

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  • グレリンによる排便促進機構

    志水 泰武, 平山 晴子, 嶋 剛士, 椎名 貴彦

    自律神経   48 ( 2 )   86 - 88   2011

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  • グレリンによる大腸運動促進機構

    平山 晴子, 椎名 貴彦, 嶋 剛士, 石見 百江, 志水 泰武

    日本病態生理学会雑誌   19 ( 1 )   28 - 33   2010.5

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  • Neuronal controls and contractile properties of esophageal muscles in neonatal rats

    Takahiko Shiina, Chiaki Nakamori, Haruko Hirayama, Takeshi Shima, Hirofumi Kuramoto, Yasutake Shimizu

    JOURNAL OF PHYSIOLOGICAL SCIENCES   60   S173 - S173   2010

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    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:SPRINGER TOKYO  

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  • MODULATORY ACTIONS OF TACHYKININS ON THE STRIATED AND SMOOTH MUSCLE MOTILITY IN THE RAT ESOPHAGUS

    Takahiko Shiina, Takeshi Shima, Haruko Hirayama, Ammar Boudaka, Juergen Woerl, Winfried L. Neuhuber, Tadashi Takewaki, Yasutake Shimizu

    JOURNAL OF PHYSIOLOGICAL SCIENCES   59   288 - 288   2009

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  • ENHANCEMENT OF COLORECTAL MOTILITY BY GHRELIN, BUT NOT DES-ACYL GHRELIN, THROUGH AN ACTIVATION OF LUMBO-SACRAL DEFECATION CENTER IN RATS

    Yasutake Shimizu, Haruko Hirayama, Takahiko Shiina, John B. Furness, Tadashi Takewaki

    JOURNAL OF PHYSIOLOGICAL SCIENCES   59   472 - 472   2009

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    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:SPRINGER TOKYO  

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  • Acylated ghrelin, but not desacyl ghrelin, enhances colorectal motility by activating lumbo-sacral defecation center in rats

    Yasutake Shimizu, Haruko Hirayama, Takahiko Shiina, John Furness, Tadashi Takewaki

    JOURNAL OF PHARMACOLOGICAL SCIENCES   106   101P - 101P   2008

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    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:JAPANESE PHARMACOLOGICAL SOC  

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Research Projects

  • 脊髄におけるグレリンの大腸運動亢進作用機構の解明

    Grant number:19K17492  2019.04 - 2023.03

    日本学術振興会  科学研究費助成事業 若手研究  若手研究

    平山 晴子

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    Grant amount:\4160000 ( Direct expense: \3200000 、 Indirect expense:\960000 )

    グレリンは、脊髄腰仙髄部の排便中枢に作用し、大腸運動を亢進する。しかし、グレリンの大腸運動亢進作用は、主にin vivoの実験系で現象としてとらえられているだけであり、その詳細なメカニズムは不明である。本研究は、脊髄におけるグレリンの大腸運動亢進作用について、脊髄から大腸に至るまでの経路における作用機序の詳細を解明することを目的とする。
    本年度は以下の実験に着手した。
    (1)グレリンの大腸における作用部位を詳細に特定:麻酔下のラットを用い、グレリンの脊髄への投与前後の大腸運動を測定し、グレリンが大腸のどの部分の運動性を変化させるのか明らかにした。
    (2)グレリンの作用発現時における神経の出力を確認:麻酔下ラットの骨盤神経に記録電極を留置し、グレリンの脊髄への投与時の、神経の複合活動電位の変化について記録を試みた。しかし神経活動の測定・記録手技が安定せず、グレリン投与時の活動電位変化記録に至ることができなかった。
    (3)脊髄神経細胞における作用を解明:グレリン投与時にその作用点である脊髄ニューロンに惹起される変化をパッチクランプ法を用いて明らかにすることを目的とし、本年度は予備実験を行った。新生ラットの腹腔内に神経標識色素を投与し、脊髄に存在する腹腔内臓器支配神経を逆行性に標識することを試みた。スライス標本の作製については技術を会得した。用いる色素の種類や投与量、新生仔の日齢等の詳細な条件を現在検討中である。

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