2024/12/20 更新

写真a

ヒラヤマ ハルコ
平山 晴子
HIRAYAMA Haruko
所属
自然生命科学研究支援センター 助教
職名
助教
外部リンク

学位

  • 博士(獣医学) ( 岐阜大学 )

研究キーワード

  • 消化管運動

  • 消化管神経系

研究分野

  • ライフサイエンス / 獣医学

  • ライフサイエンス / 実験動物学

  • ライフサイエンス / 生理学

学歴

  • 岐阜大学    

    2007年4月 - 2011年3月

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  • 岐阜大学    

    1997年4月 - 2003年3月

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経歴

  • 岡山大学   自然生命科学研究支援センター動物資源部門   助教

    2012年4月 - 現在

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  • メルボルン大学   Department of Anatomy and Cell Biology   Research Assistant

    2012年1月 - 2012年3月

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  • メルボルン大学   Department of Anatomy and Cell Biology   エンデバー奨学金によるEndeavour Research Fellow

    2011年6月 - 2011年11月

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  • あい動物クリニック

    2003年4月 - 2007年3月

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論文

  • Bacterial DNA and serum IgG antibody titer assays for assessing infection of human-pathogenic and dog-pathogenic Porphyromonas species in dogs. 国際誌

    Masako Tai-Tokuzen, Takashi Ito, Kazuya Tamura, Haruko Hirayama, Hirohito Ogawa, Shin Nakamura, Keisuke Okubo, Kazuhiro Omori, Tadashi Yamamoto, Katsumi Mominoki, Shogo Takashiba

    Heliyon   10 ( 11 )   e31872   2024年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Periodontal disease is highly prevalent in both humans and dogs. Although there have been reports of cross-infection of periodontopathic bacteria, methods for assessing it have yet to be established. The actual status of cross-infection remains to be seen. The purpose of this study was to evaluate the utility of bacterial DNA and serum immunoglobulin G (IgG) antibody titer assays to assess infection of human-pathogenic and dog-pathogenic Porphyromonas species in dogs. Four experimental beagles were used for establishing methods. Sixty-six companion dogs at veterinary clinics visiting for treatment and prophylaxis of periodontal disease were used and divided into healthy, gingivitis, and periodontitis groups. Periodontal pathogens such as Porphyromonas gingivalis and Porphyromonas gulae were investigated as target bacteria. DNA levels of both bacteria were measured using species-specific primers designed for real-time polymerase chain reaction (PCR). Serum IgG titers of both bacteria were measured by enzyme-linked immunosorbent assay (ELISA). PCR primers were confirmed to have high sensitivity and specificity. However, there was no relationship between the amount of bacterial DNA and the severity of the periodontal disease. In addition, dogs with periodontitis had higher IgG titers against both bacteria compared to dogs in the healthy and gingivitis groups; there was cross-reactivity between the two bacteria. Receiver operating characteristic (ROC) analysis of IgG titers against both bacteria showed high sensitivity (>90 %) and specificity (>75 %). Since both bacteria were distinguished by DNA assays, the combination of these assays may be useful in the evaluation of cross-infection.

    DOI: 10.1016/j.heliyon.2024.e31872

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  • Innovative submucosal injection solution for endoscopic resection with phosphorylated pullulan: a preclinical study. 国際誌

    Takuya Satomi, Yukari Ochi, Takumi Okihara, Hiroki Fujii, Yasuhiro Yoshida, Katsumi Mominoki, Haruko Hirayama, Junki Toyosawa, Yasushi Yamasaki, Seiji Kawano, Yoshiro Kawahara, Hiroyuki Okada, Motoyuki Otsuka, Akihiro Matsukawa

    Gastrointestinal endoscopy   99 ( 6 )   1039 - 1047   2024年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND AND AIMS: A submucosal injection solution is used to assist in endoscopic surgery. The high viscosity of current solutions makes them difficult to inject. In the present study, we developed an extremely low-viscosity, easy-to-use submucosal injection solution using phosphorylated pullulan (PPL). METHODS: The PPL solutions were prepared at different concentrations, and their viscosities were measured. The mucosal elevation capacity was evaluated using excised porcine stomachs. Controls included 0.4% sodium hyaluronate (SH), 0.6% sodium alginate (SA), and saline. To evaluate the practicality, the catheter injectability of 0.7% PPL was measured, and EMR and endoscopic submucosal dissection (ESD) were performed using the stomach and colorectum of live pigs. As controls, 0.4% SH and saline were used. RESULTS: The PPL solutions were of extremely low viscosity compared to the solutions of 0.4% SH and 0.6% SA. Nevertheless, the mucosal elevation capacity of PPL solutions for up to 0.7% concentration was similar to that of 0.4% SH, and 0.7% PPL was less resistant to catheter infusion than 0.4% SH and 0.6% SA. In live pig experiments with endoscopic mucosal resection and ESD, snaring after submucosal injection of 0.7% PPL was easier than with 0.4% SH, ESD with 0.7% PPL produced less bubble formation than with 0.4% SH, and the procedure time tended to be shorter with 0.7% PPL than with 0.4% SH because of the shorter injection time. CONCLUSIONS: The PPL solution is an innovative and easy-to-use submucosal injection solution.

    DOI: 10.1016/j.gie.2024.01.015

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

    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年

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    掲載種別:研究論文(学術雑誌)  

    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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  • Effects of Endoprosthesis Head Material on Acetabular Cartilage Metabolism: An Animal Study Using Crossbred Pigs.

    Shuhei Matsui, Tokifumi Majima, Katsumi Mominoki, Haruko Hirayama, Yasushi Oshima, Kenji Takahashi, Shinro Takai

    Journal of Nippon Medical School = Nippon Ika Daigaku zasshi   85 ( 6 )   309 - 314   2018年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Hip endoprosthesis is one option for the treatment of displaced femoral neck fractures and avascular necrosis of the femoral head. Few reports are available describing acetabular cartilage metabolism after endoprosthesis surgery of the hip. The purpose of this study was to compare the biological effects on cartilage between cobalt-chrome (Co-Cr) and alumina ceramic heads wherein the cartilage articulates directly. METHODS: We used the acetabular cartilage from six hips of three immature crossbred pigs to examine the effects on cytokines, the amount of hyaluronic acid (HA), and cartilage mRNA expression of ceramic head and Co-Cr head endoprosthesis. Mechanical loading of materials of Co-Cr and ceramic heads was performed on the acetabular cartilage in culture media as an organ culture model. Thereafter, protein levels of cytokines (MMP-1, 3, TNF-alpha (α), Interleukin (IL)-1 alpha (α), and IL-1 beta (β)) and the amount of HA were measured from the culture media. Cartilage RNA extraction was performed, and quantitative reverse transcriptase-polymerase chain reaction was performed with primer sets for type I, II, and III collagens; aggrecan; MMP-1, 3, 13; TNF-α; and IL-1 α, IL-1 β. RESULTS: Protein level of IL-1 β and amount of HA in the Co-Cr group were significantly higher than those of the Ceramic group. Type II collagen mRNA expression in the Ceramic group was significantly higher than in the Co-Cr group. IL-1 β mRNA expression was significantly higher in the Co-Cr group than in the Ceramic group. CONCLUSIONS: The present study showed that ceramic bipolar produces smaller adverse effects on cartilage cells compared to Co-Cr bipolar. These results could have significant implications for implant usage not only in hip joints, but also in other joints, including the shoulder, talus and radial head.

    DOI: 10.1272/jnms.JNMS.2018_85-50

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

    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年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元: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 査読

    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年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元: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 査読

    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年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元: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 査読

    Momoe Iwami, Takahiko Shiina, Haruko Hirayama, Yasutake Shimizu

    BIOMEDICAL RESEARCH-TOKYO   32 ( 2 )   181 - 185   2011年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元: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. 査読

    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年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Grains ofparadise (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 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.

    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 査読

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

    Journal of Natural Medicines   65 ( 1 )   89 - 94   2011年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    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. 査読

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

    Journal of natural medicines   65 ( 1 )   89   2011年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    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, inwhich 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 af

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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. 査読

    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年10月

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

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

    EUROPEAN JOURNAL OF PHARMACOLOGY   628 ( 1-3 )   202 - 206   2010年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    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. 査読

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

    European journal of pharmacology   628 ( 1-3 )   202 - 206   2010年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    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 wasrecorded 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[4

    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 査読

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

    JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY   2010   459789   2010年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:HINDAWI LTD  

    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. 査読

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

    Journal of biomedicine&biotechnology   2010   459789   2010年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    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 査読

    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年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元: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 査読

    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年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元: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 査読

    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年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元: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) 査読

    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年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元: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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MISC

  • 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年

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  • 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年4月

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    記述言語:日本語   出版者・発行元: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年6月

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    記述言語:日本語   出版者・発行元:(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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  • 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年

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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年

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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年

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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年5月

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    記述言語:日本語   出版者・発行元:日本病態生理学会  

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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年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元: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年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:SPRINGER TOKYO  

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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年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元: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年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:JAPANESE PHARMACOLOGICAL SOC  

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共同研究・競争的資金等の研究

  • 脊髄におけるグレリンの大腸運動亢進作用機構の解明

    研究課題/領域番号:19K17492  2019年04月 - 2024年03月

    日本学術振興会  科学研究費助成事業  若手研究

    平山 晴子

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    配分額:4160000円 ( 直接経費:3200000円 、 間接経費:960000円 )

    グレリンは、脊髄腰仙髄部の排便中枢に作用して、大腸運動を亢進する。しかしこ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のみであり、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、脊髄から大腸への経路における作用機序の詳細解明をすることを目的とする。本年度は前年度に引き続き、以下の実験を行った。
    (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、グレリンを脊髄腔内に投与した際の大腸運動を測定した。本年度以前の実験により、グレリンは大腸の直腸領域の運動を亢進させることが明らかになっており、直腸から肛門の領域について同一個体で同時に複数箇所の内圧を測定し、グレリン投与時の大腸運動について確認した。
    (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、グレリン投与時における神経の複合活動電位記録を試みた。長らく活動記録には至っていなかったが、本年度はようやく、神経活動電位と思われる記録に成功した。しかしながらまだ例数も少なく、現在、手技の安定化を目指し実験を重ねている。
    (3)脊髄神経細胞における作用を解析:パッチクランプ法を用いて、グレリンの作用点である脊髄において、ニューロンに惹起される変化を明らかにすることを試みた。神経標識色素を新生ラットの腹腔内に投与し、脊髄に存在する腹腔内臓器支配神経をあらかじめ逆行性に標識した脊髄スライス標本を作製し、パッチクランプ法により神経活動記録を行うことを目的とした。前年度の予備実験に続き、条件検討の実験を行っており、脊髄ニューロンが標識色素により染色されること、また染色される細胞の局在について確認したが、グレリン投与時の反応記録には至っていない。

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