Faculty Profiles - MIURA Naoki

Papers - MIURA Naoki

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Onishi Y, Miura N, Tanimoto A, Kawaguchi H . Methotrexate Enhances Atherosclerosis Progression via Impairment of Folate Pathway in a Microminipig Model. . In vivo (Athens, Greece)39 ( 3 ) 1262 - 1274 2025.5Methotrexate Enhances Atherosclerosis Progression via Impairment of Folate Pathway in a Microminipig Model.Reviewed International journal

Takahashi K, Arima E, Sawayama H, Suda A, Miura N, Shirakata Y, Ito S, Suda Y . Possible correlation of specific bacteria detected by using a novel screening method and periodontal disease in dogs. . The Journal of veterinary medical science 2025.4Possible correlation of specific bacteria detected by using a novel screening method and periodontal disease in dogs.Reviewed International journal

Md Nazmul Hasan, Md Mahfuzur Rahman, Al Asmaul Husna, Daiki Kato, Takayuki Nakagawa, Mohammad Arif, Naoki Miura . Hypoxia-related Y RNA fragments as a novel potential biomarker for distinguishing metastatic oral melanoma from non-metastatic oral melanoma in dogs. . The veterinary quarterly44 ( 1 ) 1 - 8 2024.12Reviewed International journal

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

Hypoxia may promote tumor progression, and hypoxically altered noncoding RNA (ncRNA) expression may play a role in metastasis. Canine oral melanoma (COM) frequently metastasizes, and ncRNA expression under hypoxia may be clinically significant. We aimed to elucidate ncRNA fragments whose expression is altered by hypoxia in COM-derived primary KMeC and metastatic LMeC cell lines using next-generation sequencing to validate these results in qRT-PCR, and then compare expression between metastatic and non-metastatic COM. The NGS analysis and subsequent qRT-PCR validation were performed using hypoxic and normoxic KMeC and LMeC cells, and clinical samples [tumor tissue, plasma, and plasma-derived extracellular vesicles] obtained from dogs with metastatic or non-metastatic melanoma were analyzed with qRT-PCR. Y RNA was significantly decreased in metastatic LMeC cells versus primary KMeC cells in hypoxic and normoxic conditions. The expression of Y RNA was decreased in dogs with metastatic melanoma versus those with non-metastatic melanoma for all clinical sample types, reflecting the pattern found with hypoxia. Receiver operating characteristic analysis demonstrated that Y RNA level is a promising biomarker for discriminating metastatic from non-metastatic melanoma in plasma [area under the curve (AUC) = 0.993, p < 0.0001] and plasma-derived extracellular vesicles (AUC = 0.981, p = 0.0002). Overall, Y RNA may be more resistant to hypoxic stress in the metastatic than the non-metastatic state for COM. However, further investigation is required to elucidate the biological functions of Y RNA under hypoxic conditions.

DOI： 10.1080/01652176.2023.2300943

Saki Hashimoto, MD Nazmul Hasan, Mohammad Arif, Nobuhiro Nozaki, Al Asmaul Husna, Yu Furusawa, Takeshi Sogawa, Kaori Takahashi, Tomohide Kuramoto, Aki Noguchi, Masashi Takahashi, Osamu Yamato, Md Mahfuzur Rahman, Naoki Miura . Aberrantly Expressed tRNA-Val Fragments Can Distinguish Canine Hepatocellular Carcinoma from Canine Hepatocellular Adenoma . Genes15 ( 8 ) 1024 - 1024 2024.8Reviewed International journal

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：MDPI AG

Hepatocellular adenoma (HCA) and hepatocellular carcinoma (HCC) can be difficult to differentiate but must be diagnosed correctly as treatment and prognosis for these tumors differ markedly. Relevant diagnostic biomarkers are thus needed, and those identified in dogs may have utility in human medicine because of the similarities between human and canine HCA and HCC. A tRNA-derived fragment (tRF), tRNA-Val, is a promising potential biomarker for canine mammary gland tumors but has not previously been investigated in hepatic tumors. Accordingly, we aimed to elucidate the potential utility of tRNA-Val as a biomarker for canine HCA and HCC using clinical samples (tumor tissue and plasma extracellular vesicles [EVs]) and tumor cell lines with qRT-PCR assays. We also investigated relevant functions and signaling pathways with bioinformatic analyses (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes). tRNA-Val was markedly downregulated in HCC tumor tissue versus HCA tumor tissue and normal liver tissue, and a similar trend was shown in plasma EVs and HCC cell lines versus healthy controls. Based on areas under the receiver operating characteristic curves (AUCs), tRNA-Val significantly distinguished HCC (AUC = 1.00, p = 0.001) from healthy controls in plasma EVs and HCC from HCA (AUC = 0.950, p = 0.01). Bioinformatics analysis revealed that tRNA-Val may be primarily involved in DNA repair, mRNA processing, and splicing and may be linked to the N-glycan and ubiquitin-mediated proteasome pathways. This is the first report on the expression of tRNA-Val in canine HCC and HCA and its possible functions and signaling pathways. We suggest that tRNA-Val could be a promising novel biomarker to distinguish canine HCC from HCA. This study provides evidence for a greater understanding of the role played by tRNA-Val in the development of canine HCC.

DOI： 10.3390/genes15081024

Yasunori Hino, Mohammad Arif, Md Mahfuzur Rahman, Al Asmaul Husna, MD Nazmul Hasan, Naoki Miura . Hypoxia-Mediated Long Non-Coding RNA Fragment Identified in Canine Oral Melanoma through Transcriptome Analysis . Veterinary Sciences11 ( 8 ) 2024.8Reviewed International journal

MD Nazmul Hasan, Md Mahfuzur Rahman, Al Asmaul Husna, Mohammad Arif, Indre Jasineviciute, Daiki Kato, Takayuki Nakagawa, Naoki Miura . Upregulation and functional roles of miR-450b in canine oral melanoma . Non-coding RNA Research9 ( 2 ) 376 - 387 2024.2Reviewed International journal

MD Nazmul Hasan, Md Mahfuzur Rahman, Al Asmaul Husna, Nobuhiro Nozaki, Osamu Yamato, Naoki Miura . YRNA and tRNA fragments can differentiate benign from malignant canine mammary gland tumors . Biochemical and Biophysical Research Communications691 149336 - 149336 2024.1Reviewed International journal

Yatsushiro R., Matsuda F., Causer B., Inoue K., Kikata J., Miura N., Hashimoto K., Akasaki Y., Unedaya K. . Using virtual fieldwork to support interprofessional and community-based learning: students from four faculties investigate life on a remote island in Japan . Frontiers in Education9 2024Reviewed International journal

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Frontiers in Education

Introduction: The Mishima Islands in Kagoshima Prefecture, Japan, are remote islands designated as medically underserved. Supporting the people living in such remote islands requires a multifaceted examination of the livelihoods of the residents, including their health, work, and living environment. Methods: Students from the faculties of nursing, veterinary science, agriculture, and engineering participated in a 3-day virtual fieldwork session held synchronously from the campus of Kagoshima University and on a remote island in the Mishima Mura island group in Kagoshima Prefecture, Japan. Coursework and post-course surveys were analyzed to determine student engagement and learning. In particular, the analysis considered learning in relation to interprofessional learning and community-based learning. Results and discussion: Students expressed being able to conduct fieldwork online, collaborate with students from multiple faculties and graduate schools, and apply their expertise. These outcomes were reflected in the five-point Likert scale evaluation responses, highlighting a sense of accomplishment and satisfaction. Virtual fieldwork can contribute to student learning by introducing new concepts and allowing them to consider development issues in remote areas from multiple perspectives.

DOI： 10.3389/feduc.2024.1421218

MD Nazmul Hasan, Md. Mahfuzur Rahman, Al Asmaul Husna, Mohammad Arif, Tomoko Iwanaga, Kyoko Tsukiyama‐Kohara, Indre Jasineviciute, Daiki Kato, Takayuki Nakagawa, Naoki Miura . Elevated expression of miR‐301a and its functional roles in canine oral melanoma . Veterinary and Comparative Oncology22 ( 1 ) 78 - 88 2023.12Reviewed International journal

KOGA Yasuhiro, SOGAWA Takeshi, SAITOH Yasuo, MIURA Naoki, NOGUCHI Aki, KURAMOTO Tomohide, FUJIKI Makoto . Case of Rib Reconstruction Using a Titanium Plate for Liposarcoma of the Thoracic Wall in a Dog . Japanese Journal of Veterinary Anesthesia & Surgery54 ( 2 ) 53 - 58 2023.10Reviewed International journal

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Japanese Society of Veterinary Anesthesia and Surgery

<p>Malignant tumors arising from thoracic wall may require extensive resection, including ribs. The major complication following rib resection is the development of a flail chest, and resection of more than six ribs is not recommended. We performed a resection with six ribs for a liposarcoma in the thoracic wall of a dog, followed by reconstruction of two cephalic ribs with a titanium plate. There was no postoperative flail chest and the patient’s respiratory status was stable. Rib reconstruction with plates was considered to allow functional reconstruction of the thoracic wall after extensive mass resection.</p>

DOI： 10.2327/jjvas.54.53

Norio Ushio, Md Nazmul Hasan, Mohammad Arif, Naoki Miura . Novel Y RNA-Derived Fragments Can Differentiate Canine Hepatocellular Carcinoma from Hepatocellular Adenoma . Animals13 ( 19 ) 2023.10Reviewed International journal

Yamada T, Kawaguchi H, Matsuoka A, Akioka K, Miura N, Izumi H, Tanimoto A . Development of a Microminipig Model of Atherosclerosis for the Evaluation of a HMGCR Inhibito . In Vivo38 ( 1 ) 98 - 106 2023.9Reviewed

Yuko Mizutani, Yoshiyuki Inoue, Yoshimichi Goda, Shinya Mizutani, Taketoshi Asanuma, Naoki Miura, Yuichi Hidaka, Reiichiro Sato, Hiroyuki Satoh . Successful Treatment of Central Nervous System Lymphoma with Combination Therapy of Nimustine and Prednisolone in Two Dogs . Veterinary Sciences10 ( 9 ) 2023.9Reviewed International journal

Indre Jasineviciute, Md Nazmul Hasan, Juozas Grigas, Arnoldas Pautienius, Arunas Stankevicius, Judita Zymantiene, Naoki Miura . microRNAs Are Abundant and Stable in Platelet-Rich Fibrin and Other Autologous Blood Products of Canines . International Journal of Molecular Sciences24 ( 1 ) 770 2023.1Reviewed International journal

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)

Various microRNAs (miRNAs) present in autologous blood products of canines have not been studied recently. We aimed to elucidate the existence of miRNAs in platelet-rich fibrin (PRF) and the stability of canine autologous blood products under various storage conditions. Total RNAs were isolated from PRF and other autologous blood products following newly adapted protocols used in commercial kits for plasma and tissue samples. Quantitative real-time polymerase chain reaction analysis (qPCR) was used to detect miRNAs in autologous blood products. The miR-16, miR-21, miR-155, and miR-146a were abundant in PRF and other autologous blood products of canines. Furthermore, we found they could maintain stability under protracted freezing temperatures of −30 °C for at least one month. Our findings revealed that PRF might be a stable resource for various canine miRNAs.

DOI： 10.3390/ijms24010770

Aki Noguchi, Tomoko Iwanaga, Naoki Miura, Takeshi Sogawa, Makoto Fujiki . Common bile duct perforation due to choledocholithiasis in a cat with gallbladder agenesis . Journal of Feline Medicine and Surgery Open Reports9 ( 1 ) 20551169221146513 2023.1Reviewed International journal

Language：Japanese Publishing type：Research paper (scientific journal)

Case summary: An 8-year-old neutered male domestic shorthair cat was presented for further investigation of anorexia, vomiting and lethargy. Abdominal ultrasonography and contrast-enhanced CT revealed choledocholithiasis with suspected bacterial peritonitis and non-visualisation of the gallbladder. During surgery, the common bile duct was noted to be perforated, and a cholelith was found in the abdominal cavity. No gallbladder was confirmed during surgery. Three months postoperatively, the cat underwent CT cholangiography and absence of the gallbladder with a vestigial duplicated gallbladder was diagnosed. Relevance and novel information: Gallbladder agenesis is extremely rare in cats, with only one previous report, but several dogs have been diagnosed based on CT cholangiography and laparoscopy. This report describes gallbladder agenesis concurrent with choledocholithiasis in an adult cat and represents the first report of CT cholangiography in a cat with gallbladder agenesis.

DOI： 10.1177/20551169221146513

Aritada Yoshimura, Takahiro Ohmori, Daiki Hirao, Miori Kishimoto, Tomoko Iwanaga, Naoki Miura, Kazuhiko Suzuki, Ryuji Fukushima . Protective Effect on Pancreatic Acinar Cell by Maintaining Cardiac Output in Canine Heart Failure Model With Decreased Pancreatic Blood Flow . Frontiers in Veterinary Science9 925847 2022.7Reviewed International journal

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Frontiers Media SA

Heart failure cause hypoperfusion-induced damage to abdominal organs due to decreased cardiac output (CO). Using a model dog with heart failure caused by rapid ventricular pacing (RVP), we have previously demonstrated that a decrease in CO reduces pancreatic blood flow (PBF). Furthermore, we have revealed that pancreatic acinar cell atrophy, which is a change in the pre-stage of pancreatitis was caused. However, the mechanism by which pancreatic acinar cell atrophy was caused in RVP dogs remains unknown. This study aimed to clarify the association between cardiac function, PBF, and histopathological changes in pancreatic acinar cells by administrating pimobendan, which increase CO, to RVP dogs. RVP dogs were divided into the control group (no medication, n = 5) and the pimobendan group (pimobendan at 0.25 mg/kg BID, n = 5). Non-invasive blood pressure measurement, echocardiography, and contrast-enhanced ultrasonography for PBF measurement were performed before initiating RVP and at 4 weeks after initiating RVP (4 weeks). At 4 weeks, the decreases in CO, mean blood pressure and PBF due to RVP were suppressed in pimobendan group. Furthermore, histopathological examination showed no changes in pancreatic acinar cells in the pimobendan group. Overall, it was clarified that the decrease in PBF due to cardiac dysfunction was a direct cause of pancreatic acinar cell atrophy. This suggests that maintaining PBF is clinically important for treating dogs with heart failure. In addition, these findings offer a reliable basis for developing new therapeutic strategies for heart failure in dogs, that is, pancreatic protection.

DOI： 10.3389/fvets.2022.925847

Yoneshige Ryuichi, Wada Mie, Honkawa Yusuke, Miura Naoki, Miyoshi Noriaki, Ando Takaaki . A clinical case of a subepiglottic cyst in a Japanese Black calf . 84 ( 7 ) 978 - 981 2022.7A clinical case of a subepiglottic cyst in a Japanese Black calfReviewed International journal

HUI-WEN CHEN, YU-CHANG LAI, MD MAHFUZUR RAHMAN, AL ASMAUL HUSNA, MD NAZMUL HASAN, HITOSHI HATAI, NORIAKI MIYOSHI, OSAMU YAMATO, NAOKI MIURA . NGS-identified miRNAs in Canine Mammary Gland Tumors Show Unexpected Expression Alterations in qPCR Analysis . In Vivo36 ( 4 ) 1628 - 1636 2022.6Reviewed International journal

Authorship：Last author,　Corresponding author Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Anticancer Research USA Inc.

Background/Aim: Canine mammary gland tumors (MGTs), as a potential model of human breast cancer, have a well-defined histological classification system. MicroRNA (miRNA) expression is a key part of the molecular signatures of both MGTs and human breast cancer, although the signatures alone do not yet provide a sufficient basis for definitive diagnosis. In this study, we investigated the association between miRNA expression patterns and histological classification. Materials and Methods: Mammary gland tissue was collected from healthy dogs (n=7) and dog patients (n=80). Further samples (n=5) were obtained from established MGT cell lines. We targeted miRNAs differentially expressed in metastatic tumor tissue versus non-metastatic and normal tissue. A subset of samples was analyzed using small RNA next generation sequencing (NGS) with subsequent qPCR. Results: Six differentially expressed miRNAs were selected from the NGS analysis and submitted for large-scale qPCR. The large-scale qPCR analysis revealed greater alternations in miRNA expression. Large-scale analysis, based on 79 samples, revealed a hierarchical clustering based on selected miRNAs that did not strikingly match the histopathological subtype classification. Conclusion: We successfully investigated the large-scale miRNA expression pattern in canine MGT and provided the whole miRNA expression. The selected miRNA demonstrated that there is no straightforward mapping between molecular signatures and histological classification of canine MGTs at the miRNA level.

DOI： 10.21873/invivo.12873

Ijiri M, Odo K, Sato M, Kawaguchi M, Fujimoto Y, Miura N, Matsuo T, Hou DX, Yamato O, Tanabe T, Kawaguchi H . Potential biomarkers for chronic seasonal heat stress in Kagoshima Berkshire pigs reared in the subtropical region . Journal of Veterinary Research66 ( 2 ) in press - 214 2022.5Reviewed International journal

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

Potential biomarkers for chronic seasonal heat stress in Kagoshima Berkshire pigs reared in the subtropical region were investigated by comparing the biomarker changes in the summer (a period of chronic heat stress) and winter (a thermoneutral period) seasons.

Pigs were allocated to summer- and winter-finishing cohorts, 12 each. The evaluations included assessment of carcass traits and internal organs’ normality carried out at the time of slaughter, and measurement of biomarkers in whole blood: derivatives of reactive oxygen metabolites (d-ROMs) and biological antioxidant potential as markers of oxidative stress, and serum amyloid A and albumin/globulin (A/G) ratio as markers of acute and chronic inflammation, respectively.

The summer-finished pigs reared under subtropical field conditions showed lower carcass quality than the winter-finished pigs, indicating a potential adverse effect of summer temperatures on the swine industry. Marginal changes were observed in d-ROMs and the A/G ratio between the summer- and winter-finishing cohorts.

The results demonstrate that d-ROMs and the A/G ratio could be used as sensitive markers for heat stress under field conditions.

Keywords
albumin/globulin ratioderivatives of reactive oxygen metabolites (d-ROMs)biological antioxidant potential (BAP)heat stressKagoshima Berkshire pigoxidative stress

DOI： 10.2478/jvetres-2022-0024

YONESHIGE Ryuichi, WADA Mie, HONKAWA Yusuke, MIURA Naoki, MIYOSHI Noriaki, ANDO Takaaki . A clinical case of a subepiglottic cyst in a Japanese Black calf . Journal of Veterinary Medical Science84 ( 7 ) 978 - 981 2022.5Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPANESE SOCIETY OF VETERINARY SCIENCE

<p>A 36-day-old Japanese Black calf exhibited wheezing associated with dyspnea from birth. Arterial blood gas analysis revealed a low oxygen partial pressure of 51 mmHg, low oxygen saturation of 83%, and high carbon dioxide partial pressure of 58.8 mmHg. Computed tomography, endoscopy, and ultrasonography showed cyst formation under the epiglottis. When the cyst was aspirated under ultrasonic guidance to secure the airway, 30 ml of viscous white turbid content was aspirated. The cyst shrank immediately after aspiration, but the wheezing and respiratory symptoms resumed 7 days after aspiration. Therefore, the cyst was surgically removed from the ventral side of the neck. No cyst remodeling was observed 30 days after surgical removal.</p>

DOI： 10.1292/jvms.22-0183

Hui Wen Chen, Yu Chang Lai, Md Mahfuzur Rahman, Al Asmaul Husna, MD Nazmul Hasan, Naoki Miura . Micro RNA differential expression profile in canine mammary gland tumor by next generation sequencing . Gene818 146237 2022.4Reviewed International coauthorship International journal

Authorship：Last author,　Corresponding author Language：Japanese Publishing type：Research paper (scientific journal)

Canine mammary gland tumors are very common and represent a potential model of human breast cancer, and microRNA (miRNAs) are promising biomarkers and therapeutic targets for these tumors. Accordingly, we aimed to identify miRNAs differentially expressed in canine mammary gland tumors using next generation sequencing (NGS), with subsequent confirmatory qPCR and target gene analyses. Mammary gland tissue was collected from healthy dogs (n=7) and dogs with suspected tumors (n=80). A subset of samples was analyzed with NGS to identify differentially expressed miRNAs with CLC Genome Workbench. Normal (n=10), tumor-adjacent (n=6), and tumor-bearing (n=76) mammary gland tissue samples were analyzed for the identified miRNAs using qPCR. An in silico analysis (TargetScan) was performed to predict the miRNAs’ target genes using gene ontology (GO) terms and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database (DAVID). We identified four miRNAs (cfa-miR-1-3p, cfa-miR-133a-3p, cfa-miR-133b-3p, and cfa-miR-133c-3p) as down regulated in canine mammary gland tumor tissues relative to normal and tumor adjacent tissues. KEGG analysis revealed the potential target genes of cfa-miR-1-3p are related to the Rap1 signaling pathway, adherens junction, and Ras signaling pathway, and those of the miR-133 family are related to the TGF-beta signaling pathway, synaptic vesicle cycle, and sphingolipid signaling pathway. In combination, these target genes are related to the regulation of transcription and DNA binding transcription (GO analysis), and the Hippo signaling pathway, adherens junction, and endocytosis (KEGG analysis). Accordingly, we suggest these four miRNAs are promising potential biomarker candidates for canine mammary gland tumors warranting further investigation.

DOI： 10.1016/j.gene.2022.146237

Al Asmaul Husna, Md Mahfuzur Rahman, Hui Wen Chen, Md Nazmul Hasan, Takayuki Nakagawa, Naoki Miura . Long non-coding RNA and transfer RNA-derived small fragments in exosomes are potential biomarkers for canine oral melanoma . Veterinary and Comparative Oncology20 ( 3 ) 653 - 663 2022.4Reviewed International coauthorship International journal

Authorship：Last author,　Corresponding author Language：Japanese Publishing type：Research paper (scientific journal)

Novel small non-coding RNAs (sRNAs) represent an emerging line of research in both human and canine oncology, due to their diverse regulatory and functional roles. Novel sRNAs are regarded as distinct from microRNAs, although both are part of the exosomal cargo. Recently, we reported on exosomal miRNAs as biomarkers for canine melanoma; however, it is unknown if novel sRNAs hold similar potential. Accordingly, we aimed to identify and validate novel sRNAs as potential biomarkers of canine oral melanoma, as part of our larger project on sequencing small exosomal RNA for this disease. Next generation sequencing revealed several differentially expressed novel sRNAs in exosomes from two melanoma cell lines (KMeC and LMeC) when compared with reference exosomes (from tumour-free dogs). Among these novel sRNAs, long noncoding RNA fragments, tRNA-derived fragments, snoRNAs and snRNAs were abundantly expressed. We selected four novel sRNAs upregulated in each cell line, and validated their aberrant expression with qPCR. In analysis using plasma-derived exosomes from melanoma patients, six out of the eight selected novel sRNAs showed significantly elevated expression. Receiver operating curve (ROC) analysis showed that one long non-coding RNA-derived small fragment (ENSCAFT00000069599.1) and one transfer RNA-derived small fragment (tRNA-Ala-TGC-5-1) have more than 85% sensitivity and specificity for differentiating melanoma patients from tumour-free dogs. Therefore, we consider that novel sRNAs may serve as candidate biomarkers to facilitate more accurate diagnosis of canine oral melanoma in clinical settings.

DOI： 10.1111/vco.12818

T. Ozawa, N. Miura, H. Hasegawa, T. Uemura, Y. Nakamoto, M. Tsujio, T. Takeuchi, M. Shiraishi . Characteristics and outcome of suspected cerebrovascular disease in dogs: 66 cases (2009-2016) . Journal of Small Animal Practice63 ( 1 ) 45 - 51 2021.9Reviewed International journal

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Wiley

Objectives : To characterise the clinical signs of suspected cerebrovascular disease in dogs. Materials and Methods : Medical records of one hospital were searched from November 2009 to December 2016 for dogs that suffered of cerebrovascular disease. We diagnosed cerebrovascular disease based on acute onset, clinical signs and magnetic resonance imaging findings. The medical history, clinical signs, concurrent disease, area of infarction, cerebrospinal fluid results, month at onset and outcome were investigated in the cerebrovascular disease group and in a control group (dogs with brain disorders other than cerebrovascular disease). Results : A total of 122 CVD cases were extracted from the 5312 patients that visited during the study period. Of these 122 cases, 66 (1.2%) matched the subject selection criteria of our study and were included in the analysis. Forebrain infarction was observed in 51 of 66 cases, of which 24 (47.1%) suffered from seizures. The number of dogs diagnosed with cerebrovascular disease was disproportionately high in August (nine of 59 cases) and December (13 of 59 cases). In the outcome survey, deterioration was observed in 11 of 55 cases. Clinical Significance : Seizure is an important clinical sign of cerebrovascular disease in dogs. There was a significant seasonal variation in the number of dogs diagnosed with cerebrovascular disease in Japan. Clinical features observed in this report differ from those of previous reports and highlight the need for additional research in this area.

DOI： 10.1111/jsap.13422

Al Asmaul Husna, Md Mahfuzur Rahman, Yu-Chang Lai, Hui-Wen Chen, Md Nazmul Hasan, Takayuki Nakagawa, Naoki Miura . Identification of melanoma-specific exosomal miRNAs as the potential biomarker for canine oral melanoma. . Pigment cell & melanoma research34 ( 6 ) 1062 - 1073 2021.7Reviewed International journal

Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

Considering the importance of the canine cancer model of human disease, as well as the need for strategies for canine cancer management, the properties of exosomes are an emerging topic in canine oncology. In our study, exosomal RNA was isolated and investigated by next-generation sequencing. We identified several differentially expressed microRNAs (miRNAs/miRs) in the exosomes of two melanoma cell lines compared with non-tumor reference exosomes. We explored these potential melanoma-specific exosomal miRNAs further and found that miR-143 and let-7b increased in primary, whereas miR-210, 708, 221, and 222 increased in metastatic site originated melanoma cells. Further analysis showed miR-143 and 221 significantly increased in plasma exosomes of metastatic melanoma patients. Moreover, the sensitivity and specificity are >85% for differentiating the non-metastatic and metastatic patients. Therefore, these miRNAs can be an incredible biomarker candidate to identify metastatic melanoma and facilitate a better prognosis.

DOI： 10.1111/pcmr.13000

Yasunori Hino, Md Mahfuzur Rahman, Yu-Chang Lai, Al Asmaul Husna, Hui-Wen Chen, Md Nazmul Hasan, Takayuki Nakagawa, Naoki Miura . Hypoxic miRNAs expression are different between primary and metastatic melanoma cells. . Gene782 145552 - 145552 2021.5Reviewed International coauthorship International journal

Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

MicroRNAs (miRNAs) can rapidly respond to cellular stresses, such as hypoxia. This immediate miRNA response regulates numerous genes and influences multiple signaling pathways. Therefore, identifying hypoxia-regulated miRNAs (HRMs) is important in canine oral melanoma (COM) to investigate their clinical significance. The hypoxic and normoxic miRNA profiles of two COM cell lines were investigated by next generation sequencing. HRMs were identified by comparing miRNA expression profiles in these cell lines with that in COM tissue. The HRM profile was different between cell lines of primary and metastatic origin, except for miR-301a and miR-8884. The time course of miRNA expression determined by qRT-PCR, especially for miR-210 and miR-301a, showed that metastatic cells are more resistant to hypoxia than primary cells. Analysis of an experimentally validated human miRNA target database revealed that miR-21 and miR-301a control a complex gene regulatory network in response to hypoxia, which includes pathways of well-known oncogenes, such as VEGF, PTEN, and TGFBR2. In conclusions, we revealed the HRM of COM. Moreover, our study shows the difference in regulation and response of hypoxic miRNAs between primary and metastatic originated melanoma cells.

DOI： 10.1016/j.gene.2021.145552

Yoshimura A, Ohmori T, Itou K, Ishi R, Matsumura Y, Wada Y, Kishimoto M, Iwanaga T, Miura N, Suzuki K, Fukushima R . Histopathological changes in the pancreas due to decreased pancreatic blood flow in a canine tachycardia-induced cardiomyopathy model. . The Journal of veterinary medical science83 ( 5 ) 780 - 783 2021.5Reviewed

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPANESE SOCIETY OF VETERINARY SCIENCE

In dogs, pancreatic acinar cell injury is thought to be caused by decreased pancreatic blood flow due to heart failure. In previous our report, it demonstrated that decreased heart function causes a significant decrease in pancreatic blood flow in heart failure dog model caused by rapid ventricular pacing (RVP). However, the types of histopathological changes remain unclear. We aimed to verify the types of histopathological changes occurring in the pancreatic tissue due to decreased heart function. After RVP for 4 weeks, atrophy of pancreatic acinar cells, characterized by a decrease in zymogen granules, was observed in all areas of the pancreas. In conclusion, the result of this study suggests that attention should be paid to ischemia/hypoperfusion injury in the pancreas.

DOI： 10.1292/jvms.20-0409

Iwanaga T, Fukushima R, Nagasato T, Maruyama I, Miura N . Analysis of blood clotting with the total thrombus analysis system in healthy dogs . J Vet Diagn Invest32 ( 2 ) 357 - 361 2021.2Analysis of blood clotting with the total thrombus analysis system in healthy dogsReviewed International journal

MOE IJIRI, YU-CHANG LAI, HIROAKI KAWAGUCHI, YOSHIKAZU FUJIMOTO, NAOKI MIURA, TOMOHIDE MATSUO, AKIHIDE TANIMOTO . NR6A1 Allelic Frequencies as an Index for both Miniaturizing and Increasing Pig Body Size . In Vivo35 ( 1 ) 163 - 167 2021.1Reviewed International journal

Nakatomi K, Ueno H, Ishikawa Y, Salim RC, Mori Y, Kanemoto I, Tancharoen S, Kikuchi K, Miura N, Omori T Okuda-Ashitaka E, Matsumura K, Imaizumi H, Motomiya Y, Maruyama I, Kawahara K . TLR4/MD-2 is a receptor for extracellular nucleophosmin 1 . Biomedical Reports14 ( 2 ) 21 - 6 2020.12Reviewed International journal

Lai YC, Habiby GH, Jasing Pathiranage CC, Rahman MM, Chen HW, Husna AA, Kubota C, Miura N . Bovine serum miR-21 expression affected by mastitis. . Res Vet Sci135 290 - 292 2020.11Bovine serum miR-21 expression affected by mastitis. Reviewed International journal

Rahman Md. Mahfuzur, Lai Yu-Chang, Al Asmaul Husna, Chen Hui-Wen, Hasan Md. Nazmul, 中川貴之, 三浦直樹 . イヌ口腔メラノーマにおける低酸素環境下でのmiRNAシグネチャーの同定(Identification of hypoxia-regulated miRNA signature in canine oral melanoma) . 日本獣医学会学術集会講演要旨集163回 290 - 290 2020.10イヌ口腔メラノーマにおける低酸素環境下でのmiRNAシグネチャーの同定(Identification of hypoxia-regulated miRNA signature in canine oral melanoma)Reviewed International journal

Al Asmaul Husna, Rahman Md. Mahfuzur, Lai Yu-Chang, Chen Hui-Wen, Hasan Md. Nazmul, 中川貴之, 三浦直樹 . イヌ口腔メラノーマにおけるエクソソームのmiRNAプロファイリング(Exosomal miRNAs profile in canine oral melanoma) . 日本獣医学会学術集会講演要旨集163回 290 - 290 2020.10イヌ口腔メラノーマにおけるエクソソームのmiRNAプロファイリング(Exosomal miRNAs profile in canine oral melanoma)Reviewed International journal

Kake S, Kawaguchi H, Nagasato T, Yamada T, Ito T, Maruyama I, Miura N*, Tanimoto A . Association Between HMGB1 and Thrombogenesis in a Hyperlipaemia-induced Microminipig Model of Atherosclerosis . In Vivo34 ( 4 ) 1871 - 1874 2020.7Association Between HMGB1 and Thrombogenesis in a Hyperlipaemia-induced Microminipig Model of AtherosclerosisReviewed

Iwanaga T, Miura N, Brainard BM, Brooks MB, Goggs R. . A Novel Microchip Flow Chamber (Total Thrombus Analysis System) to Assess Canine Hemostasis . Frontiers in Veterinary Science7 307 2020.6Reviewed

Yoshimura, A. Ohmori, T. Yamada, S. Kawaguchi, T. Kishimoto, M. Iwanaga, T. Miura, N. Fukushima, R. . Comparison of pancreatic and renal blood flow in a canine tachycardia-induced cardiomyopathy model . J Vet Med Sci 2020.4Comparison of pancreatic and renal blood flow in a canine tachycardia-induced cardiomyopathy modelReviewed

Yamazaki, H. Tanaka, T. Mie, K. Nishida, H. Miura, N. Akiyoshi, H. . Assessment of postoperative adjuvant treatment using toceranib phosphate against adenocarcinoma in dogs . J Vet Intern Med 2020.4Assessment of postoperative adjuvant treatment using toceranib phosphate against adenocarcinoma in dogsReviewed

Rahman, M. Lai, Y. C. Husna, A. A. Chen, H. W. Tanaka, Y. Kawaguchi, H. Hatai, H. Miyoshi, N. Nakagawa, T. Fukushima, R. Miura, N. . Aberrantly expressed snoRNA, snRNA, piRNA and tRFs in canine melanoma . Vet Comp Oncol 2019.11Aberrantly expressed snoRNA, snRNA, piRNA and tRFs in canine melanomaReviewed

Lai YC, Lai YT, Rahman MM, Chen HW, Husna AA, Fujikawa T, Ando T, Kitahara G, Koiwa M, Kubota C, Miura N. . Bovine milk transcriptome analysis reveals microRNAs and RNU2 involved in mastitis . FEBS J287 ( 9 ) 1899 - 1918 2019.10Bovine milk transcriptome analysis reveals microRNAs and RNU2 involved in mastitisReviewed

Rahman MM, Lai YC, Husna AA, Chen HW, Tanaka Y, Kawaguchi H, Hatai H, Miyoshi N, Nakagawa T, Fukushima R, Miura N. . Transcriptome analysis of dog oral melanoma and its oncogenic analogy with human melanoma . Oncol Rep 2019.10Transcriptome analysis of dog oral melanoma and its oncogenic analogy with human melanomaReviewed

Rahman MM, Lai YC, Husna AA, Chen HW, Tanaka Y, Kawaguchi H, Miyoshi N, Nakagawa T, Fukushima R, Miura N . Micro RNA Transcriptome Profile in Canine Oral Melanoma. . Int J Mol Sci20 ( 19 ) 2019.10Micro RNA Transcriptome Profile in Canine Oral Melanoma. Reviewed

Kawaguchi H, Horie M, Onoue K, Noguchi M, Akioka K, Masatani T, Miura N, Ozawa M, Tanimoto A . Development of a Model of Porcine Epidemic Diarrhea in Microminipigs . Vet Pathol56 ( 5 ) 711 - 714 2019.4Development of a Model of Porcine Epidemic Diarrhea in MicrominipigsReviewed

Yamada Shusaku, Hirao Daiki, Miura Naoki, Iwanaga Tomoko, Kawaguchi Takae, Yoshimura Aritada, Oomori Takahiro, Nagasato Tomoka, Maruyama Ikuro, Fukushima Ryuji . 急速心房ペーシング後の急性期における心房内と末梢領域における血液凝固性の比較(Comparison between blood coagulability in the intra-atrial and peripheral regions during the acute phase after rapid atrial pacing) . Experimental Animals68 ( 2 ) 137 - 146 2019.4急速心房ペーシング後の急性期における心房内と末梢領域における血液凝固性の比較(Comparison between blood coagulability in the intra-atrial and peripheral regions during the acute phase after rapid atrial pacing)

Publisher：(公社)日本実験動物学会

微少循環系の血流の血栓形成を総合的に評価できる総合的血栓形成評価システム(T-TAS)を用いて、心房細動を模したイヌ実験モデルの急速心房ペーシング(RAP)直後の心房内と末梢領域における血液凝固を比較した。その結果、ペーシング30分後の心房血では、ARチップ(凝固系と血小板のミックスした血栓分析のためのチップ)による+10kPaまでの凝固機能評価時間(T10)と閉塞時間(OT)の両方が、ペーシング前に比べて有意に短縮した。ペーシング30分後の心房血のPLチップ(血小板血栓分析のためのチップ)によるOTは、ペーシング前に比べて有意に短縮した。一方、末梢血ではARチップとOTチップによる、T10でもOTでもRAPによって有意な変化はなかった。以上、RAP発症30分後には血液凝集の上昇が示唆されたことから、末梢血での凝集性に変化がなかったとしても、心房細動後早期に抗血栓治療を始めたほうが良いと考えられた。

Ushio N, Rahman MM, Maemura T, Lai YC, Iwanaga T, Kawaguchi H, Miyoshi N, Momoi Y, Miura N . Identification of dysregulated microRNAs in canine malignant melanoma. . Oncol Lett 17 ( 1 ) 1080 - 1088 2019.1Identification of dysregulated microRNAs in canine malignant melanoma.Reviewed

Yamada S. Hirao D. Miura N. Iwanaga T. Kawaguchi T. Yoshimura A. Oomori T. Nagasato T. Maruyama I. Fukushima R. . Comparison between blood coagulability in the intra-atrial and peripheral regions during the acute phase after rapid atrial pacing . Exp Anim 2018.11Comparison between blood coagulability in the intra-atrial and peripheral regions during the acute phase after rapid atrial pacingReviewed

Rahman MM. Amin KB. Rahman SMM. Khair A. Rahman M. Hossain A. Rahman A. Parvez MS. Miura N. Alam MM. . Investigation of methicillin-resistant Staphylococcus aureus among clinical isolates from humans and animals by culture methods and multiplex PCR . BMC Vet Res14 ( 1 ) 300 2018.10Investigation of methicillin-resistant Staphylococcus aureus among clinical isolates from humans and animals by culture methods and multiplex PCRReviewed

Yamada S. Hirao D. Miura N. Iwanaga T. Kawaguchi T. Yoshimura A. Oomori T. Nagasato T. Maruyama I. Fukushima R. . Comparison of chronological changes in blood characteristics in the atrium and peripheral vessels after the development of non-valvular atrial fibrillation . Thromb Res171 31 - 37 2018.9Comparison of chronological changes in blood characteristics in the atrium and peripheral vessels after the development of non-valvular atrial fibrillationReviewed

Kakihana Y. Kamikokuryo C. Furubeppu H. Madokoro Y. Futatsuki T. Miyamoto S. Haraura H. Hatanaka K. Eguchi T. Saitoh Y. Miura N. Suzuki H. Ueda Y. Yasuda T. Ito T. . Monitoring of Brain Oxygenation During and After Cardiopulmonary Resuscitation: A Prospective Porcine Study . Adv Exp Med Biol1072 583 - 590 2018.9Monitoring of Brain Oxygenation During and After Cardiopulmonary Resuscitation: A Prospective Porcine StudyReviewed

Lai Y.C. . Aberrant expression of microRNAs and the miR-1/MET pathway in canine hepatocellular carcinoma . Veterinary and Comparative Oncology16 ( 2 ) 288 - 296 2018.6Invited Reviewed

Abe M, Kawaguchi H, Miura N, Akioka K, Ushikai M, Oi S, Yukawa A, Yoshikawa T, Izumi H, Horiuchi M. . Diurnal Variation of Melatonin Concentration in the Cerebrospinal Fluid of Unanesthetized Microminipig . In Vivo32 ( 3 ) 583 - 590 2018.4Diurnal Variation of Melatonin Concentration in the Cerebrospinal Fluid of Unanesthetized MicrominipigReviewed

Miura N. . Bovine radiology: technical and diagnostic basics and pitfalls . Japanese Journal of Large Animal Clinics8 ( 0 ) 269 - 275 2018Reviewed International journal

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Japanese Society of Large Animal Clinics / Large Animal Clinic Research Association

<p>　In recent years, diagnostic imaging has advanced in the veterinary field, and digital radiography has become more common in livestock animals. This review summarizes image characteristics obtained by different imaging parameters and the pitfalls of image interpretation using actual clinical cases.</p>

DOI： 10.4190/jjlac.8.269

三浦直樹 . CT検査で骨病変を確認した多発性骨髄腫の犬の症例 . 伴侶動物画像診断2 ( 6 ) 68 - 75 2017.12CT検査で骨病変を確認した多発性骨髄腫の犬の症例

Yamada Sohsuke, Kawaguchi Hiroaki, Yamada Tomonobu, Guo Xin, Matsuo Kei, Hamada Taiji, Miura Naoki, Tasaki Takashi, Tanimoto Akihide . コール酸はマイクロミニピッグにおける内臓脂肪症、アテローム性動脈硬化症、非アルコール性脂肪性肝疾患を悪化させる(Cholic Acid Enhances Visceral Adiposity, Atherosclerosis and Nonalcoholic Fatty Liver Disease in Microminipigs) . Journal of Atherosclerosis and Thrombosis24 ( 11 ) 1150 - 1166 2017.11コール酸はマイクロミニピッグにおける内臓脂肪症、アテローム性動脈硬化症、非アルコール性脂肪性肝疾患を悪化させる(Cholic Acid Enhances Visceral Adiposity, Atherosclerosis and Nonalcoholic Fatty Liver Disease in Microminipigs)

Publisher：(一社)日本動脈硬化学会

マイクロミニピッグ(μMP)を用いて、肥満、血清脂質代謝、アテローム性動脈硬化、肝傷害、肝臓、全身マクロファージ活性化に対するコール酸(CA)の影響を評価した。μMPを高脂肪/高コレステロール食(HcD)群、HcDに0.7%CAを添加(HcD+CA)群に分け、8週間飼育した。飼育前後に腹部CTを行い、血糖値、血球数、血液化学、リポ蛋白質値、血圧を測定した。全器官を切除して組織学的および免疫組織化学検査を行った。mRNA発現をリアルタイムPCRで定量した。HcD+CA群はHcD群よりも内臓脂肪症、アテローム性動脈硬化の進行、高血清酸化ストレスマーカー値を示したが、血清脂質値は同じであった。肝臓では脂質蓄積が増加し、酸化ストレスマーカーの発現が高く、泡沫性クッパー細胞と星状細胞の活性化が促進し、肝細胞アポトーシスが増加し、非アルコール性脂肪性肝疾患(NAFLD)を示した。HcD+CA群では網内系、肺毛細血管、皮膚を含む種々の器官で泡沫性マクロファージの動員が観察された。CAは局所的および全身での酸化ストレスと炎症性サイトカインを発現亢進させ、種々の器官でのマクロファージを活性化させ、内臓型肥満、アテローム性動脈硬化、NAFLDを促進させた。

Lai YC, Fujikawa T, Ando T, Kitahara G, Koiwa M, Kubota C, Miura N. . Rapid Communication: MiR-92a as a housekeeping gene for analysis of bovine mastitis-related microRNA in milk . J Anim Sci95 ( 6 ) 2732 - 2735 2017.7Reviewed

Yamazaki Hiroki, Miura Naoki, Lai Yu-Chang, Takahashi Masashi, Goto-Koshino Yuko, Momoi Yasuyuki, Nakaichi Munekazu, Tsujimoto Hajime, Setoguchi Asuka, Endo Yasuyuki . 犬における多剤耐性リンパ腫に対するリン酸トセラニブ(パラディア)の効果(Effects of toceranib phosphate(Palladia) monotherapy on multidrug resistant lymphoma in dogs) . The Journal of Veterinary Medical Science79 ( 7 ) 1225 - 1229 2017.7犬における多剤耐性リンパ腫に対するリン酸トセラニブ(パラディア)の効果(Effects of toceranib phosphate(Palladia) monotherapy on multidrug resistant lymphoma in dogs)Reviewed International journal

Yamazaki H, Miura N, Lai YC, Takahashi M, Goto-Koshino Y, Yasuyuki M, Nakaichi M, Tsujimoto H, Setoguchi A, Endo Y. . Effects of toceranib phosphate (Palladia) monotherapy on multidrug resistant lymphoma in dogs . J Vet Med Sci79 ( 7 ) 1225 - 1229 2017.6Effects of toceranib phosphate (Palladia) monotherapy on multidrug resistant lymphoma in dogsReviewed

Zahorul Islam M, Kawaguchi H, Miura N, Miyoshi N, Yamazaki-Himeno E, Shiraishi M, Miyamoto A, Tanimoto A. . Hypertension alters the endothelial-dependent biphasic response of bradykinin in isolated Microminipig basilar artery . Microvasc Res114 52 - 57 2017.6Hypertension alters the endothelial-dependent biphasic response of bradykinin in isolated Microminipig basilar arteryReviewed

Lai YC, Fujikawa T, Maemura T, Ando T, Kitahara G, Endo Y, Yamato O, Koiwa M, Kubota C, Miura N. . Inflammation-related microRNA expression level in the bovine milk is affected by mastitis . PLoS One12 ( 5 ) e0177182 2017.5Inflammation-related microRNA expression level in the bovine milk is affected by mastitisReviewed

Yamazaki H, Lai YC, Tateno M, Setoguchi A, Goto-Koshino Y, Endo Y, Nakaichi M, Tsujimoto H, Miura N. . Hypoxia-activated prodrug TH-302 decreased survival rate of canine lymphoma cells under hypoxic condition . PLoS One12 ( 5 ) e0177305 2017.5Hypoxia-activated prodrug TH-302 decreased survival rate of canine lymphoma cells under hypoxic conditionReviewed

Kiyoshi Kikuchi, Kentaro Setoyama, Ko-ichi Kawahara, Tomoka Nagasato, Takuto Terashi, Koki Ueda, Kazuki Nakanishi, Shotaro Otsuka, Naoki Miura, Hisayo Sameshima, Kazuya Hosokawa, Yoichiro Harada, Binita Shrestha, Mika Yamamoto, Yoko Morimoto-Yamashita, Haruna Kikuchi, Ryoji Kiyama, Chinatsu Kamikokuryo, Salunya Tancharoen, Harutoshi Sakakima, Motohiro Morioka, Eiichiro Tanaka, Takashi Ito, Ikuro Maruyama . Edaravone, a Synthetic Free Radical Scavenger, Enhances Alteplase-Mediated Thrombiolysis . OXIDATIVE MEDICINE AND CELLULAR LONGEVITY2017 6873281 2017

Publisher：HINDAWI LTD

The combination of alteplase, a recombinant tissue plasminogen activator, and edaravone, an antioxidant, reportedly enhances recanalization after acute ischemic stroke. We examined the influence of edaravone on the thrombolytic efficacy of alteplase by measuring thrombolysis using a newly developed microchip-based flow-chamber assay. Rat models of embolic cerebral ischemia were treated with either alteplase or alteplase-edaravone combination therapy. The combination therapy significantly reduced the infarct volume and improved neurological deficits. Human blood samples from healthy volunteers were exposed to edaravone, alteplase, or a combination of alteplase and edaravone or hydrogen peroxide. Whole blood was perfused over a collagen- and tbromboplastin-coated microchip; capillary occlusion was monitored with a video microscope and flow-pressure sensor. The area under the curve (extent of thrombogenesis or thrombolysis) at 30 minutes was 69.9% lower in the edaravone-alteplase- than alteplase-treated group. The thrombolytic effect of alteplase was significantly attenuated in the presence of hydrogen peroxide, suggesting that oxidative stress might hinder thrombolysis. D-dimers were measured to evaluate these effects in human platelet-poor plasma samples. Although hydrogen peroxide significantly decreased the elevation of D-dimers by alteplase, edaravone significantly inhibited the decrease. Edaravone enhances alteplase-mediated thrombolysis, likely by preventing oxidative stress, which inhibits fibrinolysis by alteplase in thrombi.

DOI： 10.1155/2017/6873281

Hosokawa K, Ohnishi-Wada T, Sameshima-Kaneko H, Nagasato T, Miura N, Kikuchi K, Koide T,Maruyama I, Urano T. . Plasminogen activator inhibitor type 1 in platelets induces thrombogenicity by increasing thrombolysis resistance under shear stress in an in-vitro flow chamber model . Thromb Res.146 69 - 75 2016.9Plasminogen activator inhibitor type 1 in platelets induces thrombogenicity by increasing thrombolysis resistance under shear stress in an in-vitro flow chamber modelReviewed

山﨑裕毅, 川畑貴裕, 澤真理子, 賴昱璋, 矢吹映, 三浦直樹 . 縦隔型T細胞性リンパ腫を呈した若齢犬の1例 . 日本獣医師会雑誌　69 ( 6 ) 333 - 338 2016.8縦隔型T細胞性リンパ腫を呈した若齢犬の1例Reviewed

藤川拓郎, 永野理樹, 和田三枝, 齋藤靖生, 乙丸孝之介, 三浦直樹, 藤木誠, 窪田力 . 娩出時肋骨骨折に起因した気管狭窄による呼吸不全子牛の8症例. . 日本獣医師会雑誌　69 ( 5 ) 267 - 270 2016.6娩出時肋骨骨折に起因した気管狭窄による呼吸不全子牛の8症例.Reviewed

川口博明, 笹竹洋, 野口倫子, 秋岡幸兵, 三浦直樹, 武石嘉一朗, 堀内正久, 谷本昭英 . 犬の輸送ストレス軽減のための新規鍼治療の試み. . 日本獣医師会雑誌　69 ( 3 ) 143 - 146 2016.4犬の輸送ストレス軽減のための新規鍼治療の試み.Reviewed

Morishita S, Kawaguchi H, Ono T, Miura N, Murakoshi M, Sugiyama K, Kato H, Tanimoto A, Nishino H. . Enteric lactoferrin attenuates the development of high-fat and high-cholesterol diet-induced hypercholesterolemia and atherosclerosis in Microminipigs. . Biosci Biotechnol Biochem.80 ( 2 ) 295 - 303 2016.2Enteric lactoferrin attenuates the development of high-fat and high-cholesterol diet-induced hypercholesterolemia and atherosclerosis in Microminipigs.Reviewed

Morishita Satoru, Kawaguchi Hiroaki, Ono Tomoji, Miura Naoki, Murakoshi Michiaki, Sugiyama Keikichi, Kato Hisanori, Tanimoto Akihide, Nishino Hoyoku . マイクロミニブタにおいて、腸溶性ラクトフェリンは高脂肪高コレステロール食による高コレステロール血症と粥状動脈硬化症の進行を減弱させる(Enteric lactoferrin attenuates the development of high-fat and high-cholesterol diet-induced hypercholesterolemia and atherosclerosis in Microminipigs) . Bioscience, Biotechnology, and Biochemistry80 ( 2 ) 295 - 303 2016.2マイクロミニブタにおいて、腸溶性ラクトフェリンは高脂肪高コレステロール食による高コレステロール血症と粥状動脈硬化症の進行を減弱させる(Enteric lactoferrin attenuates the development of high-fat and high-cholesterol diet-induced hypercholesterolemia and atherosclerosis in Microminipigs)Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：(公社)日本農芸化学会

マイクロミニブタに8週間腸溶性ラクトフェリン(eLF)を経口摂取させたところ、高脂肪高コレステロール食(HFCD)による血清の総コレステロール値とLDL-コレステロール値の上昇が著しく減弱したが、HDL-コレステロールは変化しなかった。血管の組織検査より、eLFにより全身の粥状動脈硬化の進行が阻害されていた。eLF投与に特徴的な肝臓の遺伝子による経路分析では、ステロイド生合成経路に有意な変化が起こり、これらの遺伝子はすべて上方制御されていた。すなわち、HFCDにより阻害されたコレステロール合成がeLFにより回復したことが示唆された。以上より、eLFはHFCDによるコレステロール代謝異常からホメオスタシスを防御することにより、高コレステロール血症と粥状動脈硬化症を防ぐことが示唆された。

山崎裕毅, 川畑貴裕, 頼いく璋, 三浦直樹 . 症例から学ぶシリーズ　縦隔型T細胞性リンパ腫を呈した若齢犬の1例 . Joncol: Japanese Journal of Veterinary Clinical Oncology12 ( 1 ) 99 - 102 2016.1症例から学ぶシリーズ　縦隔型T細胞性リンパ腫を呈した若齢犬の1例Reviewed International journal

KAWAGUCHI Hiroaki, SASATAKE Yo, NOGUCHI Michiko, AKIOKA Kohei, MIURA Naoki, TAKEISHI Ka-ichiro, HORIUCHI Masahisa, TANIMOTO Akihide . Study of a Novel Acupuncture Treatment for Canine Transportation Stress . Journal of the Japan Veterinary Medical Association69 ( 3 ) 143 - 146 2016Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：Japan Veterinary Medical Association

In recent years, animals are increasingly being transported by vehicle. The mitigation of stress animals aresubjected to while being transported by vehicle is desirable from the perspective of animal welfare. Weinvestigated the potential of acupuncture, which has fewer side effects than drug therapy, as a means fortreating canine transportation stress. Eleven dogs which had exhibited motion sickness symptoms duringtransportation (vomiting, salivation, and a reduced amount of spontaneous activity) underwent an easy-to-applyacupuncture treatment. Short, ultra-thin circular transdermal needles were applied to locations correspondingto acupoints on the apical area of both ears, which are identified as Erjian Points 1 to 3 (“Jisen” in Japanese) intraditional oriental medicine. Motion sickness symptoms were suppressed in the treated dogs the next timethey were transported. We consider acupuncture to be a promising potential therapeutic strategy in veterinarymedicine.

DOI： 10.12935/jvma.69.143

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2016&ichushi_jid=J01104&link_issn=&doc_id=20160318440004&doc_link_id=10.12935%2Fjvma.69.143&url=https%3A%2F%2Fdoi.org%2F10.12935%2Fjvma.69.143&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

YAMAZAKI Hiroki, KAWABATA Takahiro, SAWA Mariko, LAI Yu-Chang, YABUKI Akira, MIURA Naoki . A Rare Case of Mediastinal T-Cell Lymphoma in a Juvenile Dog . Journal of the Japan Veterinary Medical Association69 ( 6 ) 333 - 338 2016Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：Japan Veterinary Medical Association

Mediastinal mass and hepatomegaly were detected by computed tomography in a 10-month-old Miniature Dachshund presenting with dyspnea. The dog was diagnosed as mediastinal T-cell lymphoma with liver invasion by cytological and clonality examination. Multidrug therapy (UW-25) was not effective for the dog. As a second-line therapy, a combination treatment of toceranib phosphate and CCNU was performed based on the expression profiling of multidrug resistance genes and angiogenic genes by qRT-PCR analysis, resulting in an improved condition. However, the dog died from dyspnea at 36 days after first examination. T-cell lymphoma was confirmed by necropsy.

DOI： 10.12935/jvma.69.333

FUJIKAWA Takuro, NAGANO Masaki, WADA Mie, SAITOU Yasuo, OTOMARU Kounosuke, MIURA Naoki, FUJIKI Makoto, KUBOTA Chikara . Consideration of Diagnosis and Surgical Treatment of Tracheal Stenosis Caused by Rib Fracture in Calves . Journal of the Japan Veterinary Medical Association69 ( 5 ) 267 - 270 2016Reviewed International journal

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Japan Veterinary Medical Association

Eight Japanese black calves (14‐65 days old) with severe respiration insufficiency due to tracheal stenosis by rib fractures at the calving were brought to Kagoshima University Veterinary Teaching Hospital. At the first visit (NOSAI), all calves had common symptoms of coughing and wheezing sounds. All calves were towed at the time of calving. In x-ray and computed-tomography (CT) examinations, the 1st to 6th right and/or left ribs were fractured and tracheal stenosis was observed. Surgical treatment was conducted in all cases to remove the 1st to 3rd fractured ribs on one side that compressed the trachea. The respiratory condition of all calves improved from the day after surgical relocation and had completely reversed by the 14th postoperative day. From the above, CT examination was found to be useful for diagnosing tracheal stenosis due to rib fracture while removing the fractured ribs on one side is effective surgical treatment.

DOI： 10.12935/jvma.69.267

Kohyama M, Yabuki A, Kawasaki Y, Kawaguchi H, Miura N, Kitano Y, Onitsuka T, Rahman MM,Miyoshi N, Yamato O. . GM2 Gangliosidosis Variant 0 (Sandhoff Disease) in a Mixed-Breed Dog. . J Am Anim Hosp Assoc51 ( 6 ) 396 - 400 2015.11GM2 Gangliosidosis Variant 0 (Sandhoff Disease) in a Mixed-Breed Dog.Reviewed

Otomaru K, Fujikawa T, Saito Y, Ando T, Obi T, Miura N, Kubota C. . Diagnostic imaging of intra-abdominal cyst in heifer using the computed tomography . Journal of Veterinary Medical Science. 77 ( 9 ) 1191 - 1193 2015.9Diagnostic imaging of intra-abdominal cyst in heifer using the computed tomographyReviewed

Otomaru Konosuke, Fujikawa Takuro, Saito Yasuo, Ando Takaaki, Obi Takeshi, Miura Naoki, Kubota Chikara . 未経産牛における腹腔内嚢胞のコンピュータ断層撮影による診断(Diagnostic imaging of intra-abdominal cyst in heifer using the computed tomography) . The Journal of Veterinary Medical Science77 ( 9 ) 1191 - 1193 2015.9未経産牛における腹腔内嚢胞のコンピュータ断層撮影による診断(Diagnostic imaging of intra-abdominal cyst in heifer using the computed tomography)Reviewed International journal

Noguchi M, Miura N, Ando T, Kubota C, Hobo S, Kawaguchi H, Tanimoto A. . Profiles of reproductive hormone in the microminipig during the normal estrous cycle. . In Vivo29 ( 1 ) 17 - 22 2015.1Profiles of reproductive hormone in the microminipig during the normal estrous cycle.Reviewed

Murata D, Miyakoshi D, Hatazoe T, Miura N, Tokunaga S, Fujiki M, Nakayama K, Misumi K. . Multipotency of equine mesenchymal stem cells derived from synovial fluid. . Vet J.202 ( 1 ) 53 - 61 2014.10Multipotency of equine mesenchymal stem cells derived from synovial fluid.Reviewed

Kawaguchi H, Yamada T, Miura N, Ayaori M, Uto-Kondo H, Ikegawa M, Noguchi M, Wang KY, Izumi H, Tanimoto A. . Rapid Development of Atherosclerosis in the World's Smallest Microminipig Fed a High-Fat/High-Cholesterol Diet. . J Atheroscler Thromb21 ( 3 ) 186 - 203 2014.3Rapid Development of Atherosclerosis in the World's Smallest Microminipig Fed a High-Fat/High-Cholesterol Diet.Reviewed

Murata D. Sogawa T. Tokunaga S. Iwanaga T. Kawaguchi H. Miyoshi N. Momoi Y. Fujiki M. Miura N*（*Corresponding author）. . Ganglion cysts arising from a canine stifle joint. . J Vet Med Sci76 ( 3 ) 457 - 459 2014.3 Ganglion cysts arising from a canine stifle joint.Reviewed

Kawaguchi Hiroaki, Yamada Tomonobu, Miura Naoki, Ayaori Makoto, Uto-Kondo Harumi, Ikegawa Masaya, Noguchi Michiko, Wang Ke-Yong, Izumi Hiroyuki, Tanimoto Akihide . 高脂肪/高コレステロール食を与えた世界最小のマイクロミニブタにおける動脈硬化の急速な進行　そのサイズとヒトの病態生理学との類似性ゆえに有用な動物モデル(Rapid Development of Atherosclerosis in the World's Smallest Microminipig Fed a High-Fat/High-Cholesterol Diet: A Useful Animal Model Due to its Size and Similarity to Human Pathophysiology) . Journal of Atherosclerosis and Thrombosis21 ( 3 ) 186 - 203 2014.3高脂肪/高コレステロール食を与えた世界最小のマイクロミニブタにおける動脈硬化の急速な進行　そのサイズとヒトの病態生理学との類似性ゆえに有用な動物モデル(Rapid Development of Atherosclerosis in the World's Smallest Microminipig Fed a High-Fat/High-Cholesterol Diet: A Useful Animal Model Due to its Size and Similarity to Human Pathophysiology)Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：(一社)日本動脈硬化学会

生後3ヵ月で体重が僅か5kgの世界最小のマイクロミニブタ(MMP)を用いて脂質異常症誘発性動脈硬化の動物モデルを開発し、脂質代謝とアテローム形成に関するヒトとの類似性について調べた。MMPにコール酸以外のコレステロールを0.2%以上含む高脂肪/高コレステロール食を8週間与えたところ、高コレステロール血症となり、動脈硬化を発症した。血清のLDL-C値とLDL画分の割合は著しく増加し、LDL受容体とHMG-CoA還元酵素の肝発現は協調的に減少した。MMPの血清よりコレステロール輸送に逆の働きを及ぼすコレステリルエステル転送蛋白質活性を検出した。Niemann-Pick C1様1蛋白は肝臓と小腸で発現したが、肝性apoB mRNA編集酵素は発現しなかった。ヒトと同様、そしてマウスとは対照的に、肝性リパーゼ活性の大半は肝臓に局在していた。

Murata Daiki, Sogawa Takeshi, Tokunaga Satoshi, Iwanaga Tomoko, Kawaguchi Hiroaki, Miyoshi Noriaki, Momoi Yasuyuki, Fujiki Makoto, Miura Naoki . 犬の後膝関節に生じたガングリオン嚢胞(Ganglion Cysts Arising from a Canine Stifle Joint) . The Journal of Veterinary Medical Science76 ( 3 ) 457 - 459 2014.3犬の後膝関節に生じたガングリオン嚢胞(Ganglion Cysts Arising from a Canine Stifle Joint)Reviewed International journal

Akioka K, Kawaguchi H, Kitajima S, Miura N, Noguchi M, Horiuchi M, Miyoshi N, Tanimoto A. . Investigation of necessity of sodium cholate and minimal required amount of cholesterol for dietary induction of atherosclerosis in microminipigs. . In Vivo28 ( 1 ) 81 - 90 2014.1Investigation of necessity of sodium cholate and minimal required amount of cholesterol for dietary induction of atherosclerosis in microminipigs.Reviewed

Hosokawa K. Ohnishi T. Sameshima H. Miura N. Koide T. Maruyama I. Tanaka KA. . Comparative evaluation of direct thrombin and factor Xa inhibitors with antiplatelet agents under flow and static conditions: an in vitro flow chamber model. . PLoS One9 ( 1 ) e86491 2014.1Comparative evaluation of direct thrombin and factor Xa inhibitors with antiplatelet agents under flow and static conditions: an in vitro flow chamber model.Reviewed

Hosokawa K. Ohnishi T. Miura N. Sameshima H. Koide T. Tanaka KA. Maruyama I. . Antithrombotic effects of PAR1 and PAR4 antagonists evaluated under flow and static conditions. . Thromb Res133 ( 1 ) 66 - 72 2014.1Antithrombotic effects of PAR1 and PAR4 antagonists evaluated under flow and static conditions.Reviewed

Kawaguchi, H., Yamada, T., Miura, N., Ayaori, M., Uto-Kondo, H., Ikegawa, M., Noguchi, M., Wang, K.-Y., Izumi, H., Tanimoto, A. . Rapid development of atherosclerosis in the world's smallest microminipig fed a high-fat/high-cholesterol diet: A useful animal model due to its size and similarity to human pathophysiology . Journal of Atherosclerosis and Thrombosis21 ( 3 ) 186 - 203 2014Reviewed International journal

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

Aim: Experimental studies of human atherogenesis require an appropriate animal model that mimics human physiology and pathology. Because swine physiology is similar to human physiology, we developed a hyperlipidemia-induced atherosclerosis model using the recently developed world's smallest Microminipig (TM).
Methods: These animals weigh only 5 kg at 3 months of age, much smaller than any other miniature pig. We found that the administration of a high-fat/high-cholesterol diet containing at least 0.2% cholesterol without cholic acid for as little as eight weeks induces hypercholesterolemia and subsequent atherosclerosis in these animals.
Results: The serum levels of low-density lipoprotein cholesterol (LDL-C) and the percent distribution of cholesterol in the LDL fractions were markedly increased. The hepatic expression of LDL receptor and hydroxymethylglutaryl-CoA reductase was coordinately decreased. The cholesteryl ester transfer protein activity, which plays a role in reverse cholesterol transport, was detected in the serum of the Microminipigs. Niemann-Pick C1-like 1 protein was expressed in both the liver and small intestine; however, hepatic apoB mRNA editing enzyme was not expressed. As in humans, and in contrast to that observed in mice, most of the hepatic lipase activity was localized in the liver. These results suggest that the hyperlipidemia-induced gene expression profile linked to cholesterol homeostasis and atherogenesis is similar in Microminipigs and humans.
Conclusion: We conclude that the characteristics of the Microminipig, including its easy handling size, make it an appropriate model for studies of atherosclerosis and related conditions.

DOI： 10.5551/jat.21246

Md Zahorul Islam, Emi Yamazaki-Himeno, Mitsuya Shiraishi, Atsushi Miyamoto, Hiroaki Kawaguchi, Noriaki Miyoshi, Naoki Miura, Akihide Tanimoto . Angiotensin II decreases bradykinin-induced NO and increases prostaglandin F-2 alpha release from cultured Microminipig basilar arterial endothelial cells . JOURNAL OF PHARMACOLOGICAL SCIENCES124 104P - 104P 2014Angiotensin II decreases bradykinin-induced NO and increases prostaglandin F-2 alpha release from cultured Microminipig basilar arterial endothelial cellsReviewed International journal

Tasaki Yumi, Miura Naoki, Iyori Keita, Nishifuji Koji, Endo Yasuyuki, Momoi Yasuyuki . バベシア症の犬における血管炎様変化を伴う全身脱毛症(Generalized Alopecia with Vasculitis-Like Changes in a Dog with Babesiosis) . The Journal of Veterinary Medical Science75 ( 10 ) 1367 - 1369 2013.10バベシア症の犬における血管炎様変化を伴う全身脱毛症(Generalized Alopecia with Vasculitis-Like Changes in a Dog with Babesiosis)Reviewed International journal

Miura N, Furukawa M, Magari Y, Momoi Y. . Cross-Reactivity of the Anti-Human D-Dimer Monoclonal Antibody 1C9-6F10 to Canine Fibrin Degradation Products. . J Vet Med Sci.75 ( 7 ) 963 - 966 2013.7Cross-Reactivity of the Anti-Human D-Dimer Monoclonal Antibody 1C9-6F10 to Canine Fibrin Degradation Products.Reviewed

Miura Naoki, Furukawa Makoto, Magari Yasuo, Momoi Yasuyuki . 抗ヒトDダイマーモノクローナル抗体1C9-6F10の犬フィブリン分解産物との交差反応性(Cross-Reactivity of the Anti-Human D-dimer Monoclonal Antibody 1C9-6F10 to Canine Fibrin Degradation Products) . The Journal of Veterinary Medical Science75 ( 7 ) 963 - 966 2013.7抗ヒトDダイマーモノクローナル抗体1C9-6F10の犬フィブリン分解産物との交差反応性(Cross-Reactivity of the Anti-Human D-dimer Monoclonal Antibody 1C9-6F10 to Canine Fibrin Degradation Products)Reviewed International journal

Miura N, Kawaguchi H, Nagasato T, Yamada T, Ito T, Izumi H, Shameshima H, Miyoshi N, Tanimoto A, Maruyama I . Coagulation activity and white thrombus formation in the microminipig. . In vivo27 ( 3 ) 357 - 361 2013.5Coagulation activity and white thrombus formation in the microminipig. Reviewed

Kawaguchi H*, Yamada T*, Miura N(* Equal contribution), Noguchi M, Izumi H, Miyoshi N, Tanimoto A. . Sex Differences in Serum Lipid Profile in Novel Microminipigs. . In Vivo.27 ( 5 ) 617 - 621 2013.5Sex Differences in Serum Lipid Profile in Novel Microminipigs.Reviewed

Hosokawa K, Ohnishi T, Sameshima H, Miura N, Ito T, Koide T, Maruyama I. . nalysing responses to aspirin and clopidogrel by measuring platelet thrombus formation under arterial flow conditions. . Thromb Haemost109 ( 1 ) 102 - 111 2013.1nalysing responses to aspirin and clopidogrel by measuring platelet thrombus formation under arterial flow conditions.Reviewed

岩永朋子, 関屋仁, 三浦直樹, 桃井康行. . 咳嗽失神が認められた犬の1例. . 鹿児島県獣医師会会報52 21 - 22 2013.1 咳嗽失神が認められた犬の1例.

Yoshikawa T, Takahashi Y, Kawaguchi H, Utsunomiya S, Miura N, Izumi H, Miyoshi N, Tanimoto A. . A dermal phototoxicity study following intravenous infusion administration of ciprofloxacin hydrochloride in the novel microminipigs. . Toxicologic pathology41 ( 1 ) 109 - 113 2013.1A dermal phototoxicity study following intravenous infusion administration of ciprofloxacin hydrochloride in the novel microminipigs.Reviewed

Kikuchi K, Miura N, Kawahara KI, Murai Y, Morioka M, Lapchak PA, Tanaka E . Edaravone (Radicut), a free radical scavenger, is a potentially useful addition to thrombolytic therapy in patients with acute ischemic stroke. . Biomedical reports1 ( 1 ) 7 - 12 2013.1Reviewed International journal

Tasaki Y, Miura N, Iyori K, Nishifuji K, Endo Y, Momoi Y . Generalized Alopecia with Vasculitis-Like Changes in a Dog with Babesiosis. . J Vet Med Sci75 ( 10 ) 1367 - 1369 2013Generalized Alopecia with Vasculitis-Like Changes in a Dog with Babesiosis. Reviewed

Tasaki Yumi, Ito Genta, Miura Naoki, Tanaka Miho, Momoi Yasuyuki . Predisposing cause and prevention of canine silica urolithiasis . Journal of Pet Animal Nutrition16 ( 2 ) 61 - 66 2013Reviewed International journal

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Japanese Society of Pet Animal Nutrition

Previously, we reported that Kagoshima, Japan, is an endemic area of canine silica urolithiasis. Tap water in Kagoshima contains significantly greater silica concentrations than other areas of Japan. Ingestion of silica from tap water may lead to the formation of silica uroliths in dogs. We measured the concentration of silica in tap water from various areas of Japan. Concentrations were higher in the city of Takeda（Oita prefecture） and in some areas around the city of Chikusei（Ibaraki prefecture）. Fast atom bombardment mass spectrometry analysis of water from Kirishima（Kagoshima prefecture）revealed that the character of water was similar to that after silica sintering. Removal of silica from tap water may decrease the risk of silica urolithiasis in dogs. We demonstrated that silica could be successfully removed from tap water with a reverse osmosis membrane water filter but not with a typical domestic water filter. We also sent internet-based questionnaires to owners of dogs with silica uroliths to investigate other possible etiologies of silica urolithiasis. The results revealed that the specific pet food brand may be related to silica urolithiasis. However, the concentration of total silica in pet food does not appear to be related to the formation of uroliths.

DOI： 10.11266/jpan.16.61

Kikuchi, K., Tancharoen, S., Ito, T., Morimoto-Yamashita, Y., Miura, N., Kawahara, K.-i., Maruyama, I., Murai, Y., Tanaka, E. . Potential of the angiotensin receptor blockers (ARBs) telmisartan, irbesartan, and candesartan for inhibiting the HMGB1/RAGE axis in prevention and acute treatment of stroke . International Journal of Molecular Sciences14 ( 9 ) 18899 - 18924 2013Reviewed International journal

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

Stroke is a major cause of mortality and disability worldwide. The main cause of stroke is atherosclerosis, and the most common risk factor for atherosclerosis is hypertension. Therefore, antihypertensive treatments are recommended for the prevention of stroke. Three angiotensin receptor blockers (ARBs), telmisartan, irbesartan and candesartan, inhibit the expression of the receptor for advanced glycation end-products (RAGE), which is one of the pleiotropic effects of these drugs. High mobility group box 1 (HMGB1) is the ligand of RAGE, and has been recently identified as a lethal mediator of severe sepsis. HMGB1 is an intracellular protein, which acts as an inflammatory cytokine when released into the extracellular milieu. Extracellular HMGB1 causes multiple organ failure and contributes to the pathogenesis of hypertension, hyperlipidemia, diabetes mellitus, atherosclerosis, thrombosis, and stroke. This is the first review of the literature evaluating the potential of three ARBs for the HMGB1-RAGE axis on stroke therapy, including prevention and acute treatment. This review covers clinical and experimental studies conducted between 1976 and 2013. We propose that ARBs, which inhibit the HMGB1/RAGE axis, may offer a novel option for prevention and acute treatment of stroke. However, additional clinical studies are necessary to verify the efficacy of ARBs.

DOI： 10.3390/ijms140918899

Miyamoto Atsushi, Islam Md. Zahorul, Kawaguchi Hiroaki, Miura Naoki, Yamzaki-Himeno Emi, Shiraishi Mitsuya, Miyoshi Noriaki, Tanimoto Akihide . Effect of continuous intravenous infusion of angiotensin II on Microminipig basilar arterial responsiveness . JOURNAL OF PHARMACOLOGICAL SCIENCES121 22P 2013Reviewed International journal

Hosokawa, K., Ohnishi, T., Sameshima, H., Miura, N., Ito, T., Koide, T., Maruyama, I. . Analysing responses to aspirin and clopidogrel by measuring platelet thrombus formation under arterial flow conditions . Thrombosis and Haemostasis109 ( 1 ) 102 - 111 2013Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN

High residual platelet aggregability and circulating platelet-monocyte aggregates in patients administered aspirin and clopidogrel are associated with ischaemic vascular events. To determine the relevance of these factors with residual thrombogenicity, we measured platelet thrombus formation using a microchip-based flow-chamber system in cardiac patients receiving aspirin and/or clopidogrel, and evaluated its correlation with agonist-inducible platelet aggregation and platelet-monocyte aggregates. Platelet thrombus formation was analysed by measuring flow pressure changes due to the occlusion of micro-capillaries and was quantified by calculating AUC(10) (area under the flow pressure curve). The growth and stability of platelet thrombi that formed inside microchips at shear rates of 1000, 1500, and 2000 s(-1) were markedly reduced in patients receiving aspirin and/or thienopyridine compared to healthy controls (n=33). AUC(10) values of aspirin therapy patients (n=20) were significantly lower and higher than those of healthy controls and dual antiplatelet therapy patients (n=19), respectively, and showed relatively good correlations with collagen-induced platelet aggregation and platelet-monocyte aggregates at 1000 and 1500 s(-1) (r(s)>0.59, p<0.01). In contrast, AUC(10) in dual antiplatelet therapy patients was significantly correlated with ADP-induced platelet aggregation at all examined shear rates (r(s)>0.59, p<0.01), but did not correlate with collagen-induced aggregation. Aspirin monotherapy patients with high residual platelet thrombogenicity also exhibited significant elevations in both collagen-induced platelet aggregation and platelet-monocyte aggregates. Our results, although preliminary, suggest that residual platelet thrombogenicity in aspirin-treated patients is associated with either collagen-induced platelet aggregation or circulating platelet-monocyte aggregates, but it is predominantly dependent on ADP-induced platelet aggregation in patients receiving dual antiplatelet therapy.

DOI： 10.1160/TH12-06-0441

濱田亜衣, 三浦直樹, 桃井康行 . 犬の中枢性リンパ腫の遺伝子診断 . MVM21 ( 7 ) 45 - 48 2012.11犬の中枢性リンパ腫の遺伝子診断Reviewed International journal

Murata D, Miura N*,（*Corresponding author）, Iwanaga T, Tokunaga S, Miyoshi N, Kitano Y, Momoi Y, and Fujiki M, . CT and MRI Imaging Diagnosis of Epidural Idiopathic Sterile Pyogranulomatous Inflammation in a Dog Spinal Canal. . J Vet Med Sci74 ( 7 ) 913 - 915 2012.7CT and MRI Imaging Diagnosis of Epidural Idiopathic Sterile Pyogranulomatous Inflammation in a Dog Spinal Canal.Reviewed

Iwanaga T, Miura N, Miyoshi N, Endo Y, and Momoi Y. . Abnormal Erythroid Cell Proliferation and Myelofibrosis in a Cat. . J Vet Med Sci74 ( 7 ) 909 - 912 2012.7Abnormal Erythroid Cell Proliferation and Myelofibrosis in a Cat. Reviewed

Kawaguchi H, Yamada T, Miura N, Takahashi Y, Yoshikawa T, Izumi H, Kawarasaki T, Miyoshi N, and Tanimoto A. . Reference Values of Hematological and Biochemical Parameters for the World Smallest Microminipigs. . J Vet Med Sci74 ( 7 ) 933 - 936 2012.7Reference Values of Hematological and Biochemical Parameters for the World Smallest Microminipigs.Reviewed

Murata Daiki, Miura Naoki, Iwanaga Tomoko, Tokunaga Satoshi, Miyoshi Noriaki, Kitano Yoshiaki, Momoi Yasuyuki, Fujiki Makoto . イヌ脊柱管における硬膜外特発性無菌性化膿性肉芽腫性炎症のCTおよびMRIイメージング診断(CT and MRI Imaging Diagnosis of Epidural Idiopathic Sterile Pyogranulomatous Inflammation in a Dog Spinal Canal) . The Journal of Veterinary Medical Science74 ( 7 ) 913 - 915 2012.7イヌ脊柱管における硬膜外特発性無菌性化膿性肉芽腫性炎症のCTおよびMRIイメージング診断(CT and MRI Imaging Diagnosis of Epidural Idiopathic Sterile Pyogranulomatous Inflammation in a Dog Spinal Canal)Reviewed International journal

Kawaguchi Hiroaki, Yamada Tomonobu, Miura Naoki, Takahashi Yoshihiro, Yoshikawa Tsuyoshi, Izumi Hiroyuki, Kawarasaki Tatsuo, Miyoshi Noriaki, Tanimoto Akihide . 世界最小ミニブタにおける血液学的および生化学的パラメーターの基準値(Reference Values of Hematological and Biochemical Parameters for the World Smallest Microminipigs) . The Journal of Veterinary Medical Science74 ( 7 ) 933 - 936 2012.7世界最小ミニブタにおける血液学的および生化学的パラメーターの基準値(Reference Values of Hematological and Biochemical Parameters for the World Smallest Microminipigs)Reviewed International journal

Iwanaga Tomoko, Miura Naoki, Miyoshi Noriaki, Endo Yasuyuki, Momoi Yasuyuki . ネコにおける異常赤血球系細胞増殖と骨髄線維症(Abnormal Erythroid Cell Proliferation and Myelofibrosis in a Cat) . The Journal of Veterinary Medical Science74 ( 7 ) 909 - 912 2012.7ネコにおける異常赤血球系細胞増殖と骨髄線維症(Abnormal Erythroid Cell Proliferation and Myelofibrosis in a Cat)Reviewed International journal

田崎由実, 三浦直樹, 桃井康行 . 鹿児島県で多発するイヌのシリカ尿石についての緊急調査 . ペット栄養学会誌15 ( 1 ) 7 - 11 2012.4鹿児島県で多発するイヌのシリカ尿石についての緊急調査Reviewed International journal

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：(一社)日本ペット栄養学会

シリカ結石はイヌではまれな尿石とされている。今回、我々は鹿児島県を中心にシリカ尿結石について疫学調査を行った。その結果、鹿児島県内の獣医師やオーナーに対するアンケート調査において、鹿児島県を中心とする地域でシリカ尿結石が多くみられ、その発生の要因として飲料水との関係が示唆された。そこで鹿児島県内の水道水中のシリカ濃度を測定したところ、他地域と比較して著しく高値を示した。またミネラルウォーターについても同様に、鹿児島県が採水地の製品でシリカ濃度が高値のものがあった。実験的にシリカを高濃度に含む水道水の飲水により尿中シリカ濃度の上昇は見られなかったが、疫学調査から、シリカ濃度の低い水を飲水として使用することがシリカ結石発生の予防となると推測した。(著者抄録)

三浦直樹 . 大学病院の二次診療　鹿児島大学農学部附属動物病院<第1回>　当施設における画像診断科の状況ならびにダイナミックCT造影検査の症例紹介 . CLINIC NOTE8 ( 2 ) 90 - 94 2012.2大学病院の二次診療　鹿児島大学農学部附属動物病院<第1回>　当施設における画像診断科の状況ならびにダイナミックCT造影検査の症例紹介Reviewed International journal

Tasaki Yumi, Miura Naoki, Momoi Yasuyuki . Silica urolithiasis in dogs around in Kagoshima . Journal of Pet Animal Nutrition15 ( 1 ) 7 - 11 2012Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：Japanese Society of Pet Animal Nutrition

Silica calculus is unusual in urolithiasis in dogs. We conducted epidemiological study on silica calculus in dogs around Kagoshima area. Information questionnaires from veterinarians and clients indicated that silica urolithiasis was not related to food and dog's habit (eating clod), but was associated with drinking tap water. Silica concentration of tap water in Kagoshima area was obviously higher than that in another area in Japan. A brand of mineral water made in Kagoshima area also had high silica level. Though intake of high level silica in water did not affect urine silica concentration experimentally, our results indicated that it is beneficial to use low silica level water to prevent silica urolithiasis in dogs.

DOI： 10.11266/jpan.15.7

田崎由実, 伊藤源太, 三浦直樹, 桃井康行 . 犬のシリカ尿結石好発地域におけるシリカ結石の成因と予防方法 . ペット栄養学会誌15 ( 0 ) Suppl_44 - Suppl_45 2012Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：日本ペット栄養学会

シリカ結石はイヌでは比較的まれな尿石とされている。昨年の本学会で、我々は鹿児島県ではシリカ尿結石が多くみられることを報告した。そして、鹿児島県内の水道水中のシリカ濃度は他の地域に較べ著しく高く、シリカ結石発生の要因として飲料水との関係を示唆した。しかし、新たな謎も生じた。鹿児島市内の水道水のシリカ濃度は比較的高いのになぜシリカ結石がほとんど生じないか、シリカの好発地帯ではみな同じ水を飲んでいるのにもかかわらずなぜ一部の犬でシリカ結石が生じるのか、さらに、シリカ好発地域以外では何が原因でシリカ結石が発症するのか、などである。今回はそれらの謎に答えるため各種実験を行い、シリカ発生の機序とその予防法について考察した。

DOI： 10.11266/jpan.15.Suppl_44

Kikuchi, K., Takeshige, N., Miura, N., Morimoto, Y., Ito, T., Tancharoen, S., Miyata, K., Kikuchi, C., Iida, N., Uchikado, H., Miyagi, N., Shiomi, N., Kuramoto, T., Maruyama, I., Morioka, M., Kawahara, K.-I. . Beyond free radical scavenging: Beneficial effects of edaravone (Radicut) in various diseases (Review) . Experimental and Therapeutic Medicine3 ( 1 ) 3 - 8 2012Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

Free radicals play an important role in the pathogenesis of a variety of diseases; thus, they are an attractive target for therapeutic intervention in these diseases. Compounds capable of scavenging free radicals have been developed for this purpose and some, developed for the treatment of cerebral ischemic stroke, have progressed to clinical trials. One such scavenger, edaravone, is used to treat patients within 24 h of stroke. Edaravone, which can diffuse into many disease-affected organs, also shows protective effects in the heart, lung, intestine, liver, pancreas, kidney, bladder and testis. As well as scavenging free radicals, edaravone has antiapoptotic, anti-necrotic and anti-cytokine effects in various diseases. Here, we critically review the literature on its clinical efficacy and examine whether edaravone should be considered a candidate for worldwide development, focusing on its effects on diseases other than cerebral infarction. Edaravone has been safely used as a free radical scavenger for more than 10 years; we propose that edaravone may offer a novel treatment option for several diseases.

DOI： 10.3892/etm.2011.352

KIKUCHI KIYOSHI, KAWAHARA KO-ICHI, MATSUDA FUMIYO, ITO TAKASHI, MORIMOTO YOKO, TANCHAROEN SALUNYA, MIURA NAOKI, TAKESHIGE NOBUYUKI, ORITO KIMIHIKO, YAMASHITA SHIN, UCHIKADO HISAAKI, MIYAGI NAOHISA, SHIOMI NAOTO, KURAMOTO TERUKAZU, TOKUTOMI TAKASHI, SHIGEMORI MINORU, SAKAMOTO ROKUDAI, KIKUCHI CHIEMI, IIDA NARUMI, YOSHIDA YOSHIHIRO, HASHIGUCHI TERUTO, MARUYAMA IKURO, MORIOKA MOTOHIRO, TANAKA EIICHIRO . Effect of edaravone on HMGB1 in neuronal cells under ischemic conditions . Neurotraumatology34 ( 2 ) 225 - 227 2011.12Reviewed International journal

西洋志、徳永暁、三浦直樹 . ダイナミックCT撮影が診断・治療法の選択に有用であった犬の肝細胞癌の2例. . 鹿児島県獣医師会雑誌48 15 - 17 2011.10ダイナミックCT撮影が診断・治療法の選択に有用であった犬の肝細胞癌の2例.

岩永朋子, 三浦直樹, 新井恒, 桃井康行, 遠藤泰之． , 26(47): 22-24 (2011) . ドキソルビシン投与後に心筋障害が原因と思われる不整脈が発症した2症例． . 鹿児島県獣医師会会報26 ( 47 ) 22 - 24 2011.10ドキソルビシン投与後に心筋障害が原因と思われる不整脈が発症した2症例．

MURATA Daiki, MIURA Naoki, MATUMOTO Mitsuharu, MIYOSHI Nobuaki, FUJIKI Makoto, MISUMI Kazuhiro . Diagnostic Imaging of Cervical Vertebral Injury in a Horse . Journal of the Japan Veterinary Medical Association64 ( 9 ) 703 - 707 2011.9Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：Japan Veterinary Medical Association

An equine case of hind lameness and wobbler syndrome following an accidental forward fall during exercise was evaluated by diagnostic imaging. The myelography under general anesthesia was suggestive of a dorsally compressed spine between the sixth cervical vertebrae (C6) and C7. Histopathological findings also pointed to compression myelopathy between C6 and C7. A computed tomography scan of the cervical and thoracic (T) vertebraes following euthanasia was diagnostic of fractures of the C7 and joint space widening at the articular processes at the range from C6 to T2. Deformed alignment from C6 to T2 could induce spinal compression.

DOI： 10.12935/jvma.64.703

Other Link： http://agriknowledge.affrc.go.jp/RN/2010814357

Kikuchi K, Uchikado H, Miyagi N, Morimoto Y, Ito T, Tancharoen S, Miura N, Miyata K, Sakamoto R, Kikuchi C, Iida N, Shiomi N, KuramotoT, Kawahara K. . Beyond neurological disease: New targets for edaravone. . Int J Mol Med. 28 ( 6 ) 899 - 906 2011.6Beyond neurological disease: New targets for edaravone.Reviewed

Kikuchi K, Uchikado H, Miura N, Morimoto Y, Ito T, Tancharoen S, Miyata K, Sakamoto R, Kikuchi C, Iida N, Shiomi N, KuramotoT, Miyagi N, Kawahara K . HMGB1 as a therapeutic target in spinal cord injury: A hypothesis for novel therapy development. . Exp Ther Med2 ( 5 ) 767 - 770 2011.5HMGB1 as a therapeutic target in spinal cord injury: A hypothesis for novel therapy development.Reviewed

三浦直樹 . ダイナミックCT造影検査による門脈体循環シャント症例の診断. . 鹿児島県獣医師会雑誌26 ( 1 ) 20 - 21 2011.3ダイナミックCT造影検査による門脈体循環シャント症例の診断.

Kawaguchi H, Miyoshi N, Miura N, Fujiki M, Horiuchi M, Izumi Y, Miyajima H, Nagata R, Misumi K, Takeuchi T, Tanimoto A, Yoshida H . Microminipig, a Non-rodent Experimental Animal Optimized for Life Science Research:Novel Atherosclerosis Model Induced by High Fat and Cholesterol Diet. . J Pharmacol Sci.115 ( 2 ) 115 - 121 2011.2Microminipig, a Non-rodent Experimental Animal Optimized for Life Science Research:Novel Atherosclerosis Model Induced by High Fat and Cholesterol Diet.Reviewed

Kikuchi K*, Miura N*, (*These authors are equally contributed.) Morimoto Y, Ito T, Tancharoen S, Miyata K, Kikuchi C, Iida N, Takeshige N, Uchikado H, Miyagi N, Shiomi N, KuramotoT, Hashiguchi T, Maruyama I, Morioka M, Kawahara K. . Beneficial Effects of the Free Radical Scavenger Edaravone (Radicut) in Neurologic Diseases. . J Neurol Neurophysiol 1 ( Special Issue 1 ) 1 - 5 2011.1Beneficial Effects of the Free Radical Scavenger Edaravone (Radicut) in Neurologic Diseases.Reviewed

田崎由実, 三浦直樹, 桃井康行 . 鹿児島県で多発するイヌのシリカ結石についての報告 . ペット栄養学会誌14 ( 0 ) Suppl_73 - Suppl_74 2011Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：日本ペット栄養学会

シリカ結石はイヌではまれな尿石とされている。今回、我々は鹿児島県を中心にシリカ尿結石について疫学調査を行った。その結果、鹿児島県内の獣医師やオーナーに対するアンケート調査において、鹿児島県を中心とする地域でシリカ尿結石が多くみられ、その発生の要因として飲料水との関係が示唆された。そこで鹿児島県内の水道水中のシリカ濃度を測定したところ、他地域と比較して著しく高値を示した。またミネラルウォーターについても同様に、鹿児島県が採水地の製品でシリカ濃度が高値のものがあった。実験的にシリカを高濃度に含む水道水の飲水により尿中シリカ濃度の上昇は見られなかったが、疫学調査から、シリカ濃度の低い水を飲水として使用することがシリカ結石発生の予防となると推測した。

DOI： 10.11266/jpan.14.Suppl_73

Meng, X., Kawahara, K.-I., Miyanohara, H., Yoshimoto, Y., Yoshinaga, K., Noma, S., Kikuchi, K., Morimoto, Y., Ito, T., Oyama, Y., Yoshinaga, N., Shrestha, B., Chandan, B., Mera, K., Tada, K.-I., Miura, N., Ono, Y., Takenouchi, K., Maenosono, R., Nagasato, T., Hashiguchi, T., Maruyama, I. . 1,5-anhydro-D-fructose: A natural antibiotic that inhibits the growth of gram-positive bacteria and microbial biofilm formation to prevent nosocomial infection . Experimental and Therapeutic Medicine2 ( 4 ) 625 - 628 2011Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

Nosocomial infections caused by microbial opportunistic infections or microbial biofilms may occur during hospitalization and increase patient morbidity, mortality and health care costs. Artificial antibiotic agents were initially used to prevent infection; however, the high prevalence of nosocomial infections has resulted in their excessive use, which has led to microbial resistance to these agents. The increase in microbial resistance to antibiotics and the development of antibiotic agents may be the cause of the production of other microbial resistance. Thus, natural compounds that have no adverse side effects would be a preferred treatment modality. Recently, the monosaccharide 1,5-anhydro-D-fructose (1,5-AF), a natural plant compound derived from starch, has been found to have multifunctional properties, including antioxidant, antiplatelet aggregation by thrombin and anti-inflammatory activities. The results of the present study demonstrate that 1,5-AF suppressed the growth of coagulase-negative staphylococci on the hands as well as the growth of Staphylococcus epidermidis, which is a cause of opportunistic infections. Furthermore, 1,5-AF suppressed biofilm formation by the methicillin-resistant Staphylococcus aureus. In conclusion, 1,5-AF is a natural compound that may be effective in preventing nosocomial infections, without causing adverse side effects.

DOI： 10.3892/etm.2011.245

Kikuchi, K., Kawahara, K.-I., Uchikado, H., Miyagi, N., Kuramoto, T., Miyagi, T., Morimoto, Y., Ito, T., Tancharoen, S., Miura, N., Takenouchi, K., Oyama, Y., Shrestha, B., Matsuda, F., Yoshida, Y., Arimura, S., Mera, K., Tada, K.-I., Yoshinaga, N., Maenosono, R., Ohno, Y., Hashiguchi, T., Maruyama, I., Shigemori, M. . Potential of edaravone for neuroprotection in neurologic diseases that do not involve cerebral infarction (Review) . Experimental and Therapeutic Medicine2 ( 5 ) 771 - 775 2011Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

Edaravone was originally developed as a potent free radical scavenger and has been widely used to treat cerebral infarction in Japan since 2001. Several free radical scavengers have been developed and some of them have progressed to clinical trials for the treatment of cerebral infarction. One such scavenger, edaravone, has been approved by the regulatory authority in Japan for the treatment of patients with cerebral infarction. Of particular interest is the ability of edaravone to diffuse into the central nervous system in various neurologic diseases. Aside from its hydroxyl radical scavenging effect, edaravone has been found to have beneficial effects on inflammation, matrix metalloproteinases, nitric oxide production and apoptotic cell death. Concordantly, edaravone has been found to have neuroprotective effects in a number of animal models of disease, including stroke, spinal cord injury, traumatic brain injury, neurodegenerative diseases and brain tumors. The proven safety of edaravone following 9 years of use as a free radical scavenger suggests that it may have potential for development into an effective treatment of multiple neurologic conditions in humans.

DOI： 10.3892/etm.2011.281

Kawaguchi Hiroaki, Miyoshi Noriaki, Miura Naoki, Horiuchi Masahisa, Ono Tomoji, Murakoshi Michiaki, Nishino Hoyoku, Nagata Ryoichi, Sahara Hisashi, Tanimoto Akihide, Yamada Kazuhiko, Yoshida Hiroki . Microminipig: research models to break through cardiovascular disease . JOURNAL OF PHARMACOLOGICAL SCIENCES115 49P 2011Reviewed International journal

Kikuchi, K., Uchikado, H., Miura, N., Morimoto, Y., Ito, T., Tancharoen, S., Miyata, K., Sakamoto, R., Kikuchi, C., Iida, N., Shiomi, N., Kuramoto, T., Miyagi, N., Kawahara, K.-I. . HMGB1 as a therapeutic target in spinal cord injury: A hypothesis for novel therapy development (Review) . Experimental and Therapeutic Medicine2 ( 5 ) 767 - 770 2011Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

Historically, clinical outcomes following spinal cord injury (SCI) have been dismal. Severe SCI leads to devastating neurological deficits, and there is no treatment available that restores the injury-induced loss of function to a degree that an independent life can be guaranteed. To address all the issues associated with SCI, a multidisciplinary approach is required, as it is unlikely that a single approach, such as surgical intervention, pharmacotherapy or cellular transplantation, will suffice. High mobility group box 1 (HMGB1) is an inflammatory cytokine. Various studies have shown that HMGB I plays a critical role in SCI and that inhibition of HMGB1 release may be a novel therapeutic target for SCI and may support spinal cord repair. In addition, HMGB1 has been associated with graft rejection in the early phase. Therefore, HMGB1 may be a promising therapeutic target for SCI transplant patients. We hypothesize that inhibition of HMGB1 release rescues patients with SCI. Taken together, our findings suggest that anti-HMGB1 monoclonal antibodies or short hairpin RNA-mediated HMGB1 could be administered for spinal cord repair in SCI patients.

DOI： 10.3892/etm.2011.310

Kikuchi, K., Uchikado, H., Miyagi, N., Morimoto, Y., Takashi, I., Tancharoen, S., Miura, N., Miyata, K., Sakamoto, R., Kikuchi, C., Iida, N., Shiomi, N., Kuramoto, T., Kawahara, K.-I. . Beyond neurological disease: New targets for edaravone (Review) . International Journal of Molecular Medicine28 ( 6 ) 899 - 906 2011Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

Free radicals play major roles in the pathogenesis of tissue damage in many diseases and clinical conditions, and the removal of free radicals may offer a treatment option. Several modulators of free radical scavenger pathways have been developed and some have progressed to clinical trials. One such agent, edaravone, was approved in 2001 in Japan for the treatment of cerebral infarction. It has since been shown that edaravone can diffuse into many organs and, in addition to its effects on hydroxyl radical removal, edaravone modulates inflammatory processes, matrix metalloproteinase levels, nitric oxide production, apoptotic cell death, and necrotic cell death. Edaravone also exerts protective effects in a number of animal models of disease and tissue damage, including models of myocardial, lung, intestinal, liver, pancreatic and renal injury. Together with the proven safety of edaravone following 9 years of use as a modulator of free radical scavenging pathways in neurological disease, these additional effects of edaravone suggest that it may offer a novel treatment for several non-neurological diseases and clinical conditions in humans.

DOI： 10.3892/ijmm.2011.795

KIKUCHI KIYOSHI, KAWAHARA KO-ICHI, UCHIKADO HISAAKI, MIYAGI NAOHISA, KURAMOTO TERUKAZU, MIYAGI TOMOYA, MORIMOTO YOKO, ITO TAKASHI, TANCHAROEN SALUNYA, MIURA NAOKI, MIYATA KEI, KIKUCHI CHIEMI, SAKAMOTO ROKUDAI, SHIOMI NAOTO, HASHIGUCHI TERUTO, MARUYAMA IKURO, TOKUTOMI TAKASHI, SHIGEMORI MINORU . Minocycline attenuates both OGD-induced HMGB1 release and HMGB1-induced apoptosis in ischemic neuronal injury in PC12 cells . Neurotraumatology33 ( 2 ) 241 - 243 2010.12Reviewed International journal

Kikuchi K, Kawahara KI, Miyagi N, Uchikado H, Kuramoto T, Morimoto Y, Tancharoen S, Miura N, Takenouchi K, Oyama Y, Shrestha B, Matsuda F, Yoshida Y, Arimura S, Mera K, Tada KI, Yoshinaga N, Maenosono R, Ohno Y, Hashiguchi T, Maruyama I, Shigemori M. . Edaravone: A new therapeutic approach for the treatment of acute stroke. . Med Hypotheses.75 ( 6 ) 583 - 585 2010.12Edaravone: A new therapeutic approach for the treatment of acute stroke.Reviewed

Miyoshi N, Horiuchi M, Inokuchi Y, Miyamoto Y, Miura N, Tokunaga S, Fujiki M, Izumi Y, Miyajima H, Nagata R, Misumi K, Takeuchi T, Tanimoto A, Yasuda N, Yoshida H and Kawaguchi H. . Novel Microminipig Model of Atherosclerosis by High Fat and High Cholesterol Diet, Established in Japan. . In Vivo24 ( 5 ) 671 - 680 2010.9Novel Microminipig Model of Atherosclerosis by High Fat and High Cholesterol Diet, Established in Japan.Reviewed

Kikuchi K, Kawahara K, Tsuji C, Tajima Y, Kuramoto T, Shihara M, Koga Y, Shiomi N, Uchikado H, Morimoto Y, Miura N, Mera K, Ohno Y, Miyagi N, Hashiguchi T, Maruyama I, Hayabuchi N, Nakayama K, Shigemori M . Post mortem contrast-enhanced computed tomography in a case of sudden death from acute pulmonary thromboembolism. . Experimental and Therapeutic Medicine1 ( 3 ) 503 - 505 2010.5Post mortem contrast-enhanced computed tomography in a case of sudden death from acute pulmonary thromboembolism.Reviewed

KikuchiK, Kawahara K, Biswas KK, Ito T, Tancharoen S, Shiomi N, Koda Y, Matsuda F, Morimoto Y, Oyama Y, Takenouchi K, Miura N, Arimura N, Nawa Y, Arimura S, Jie MX, Shrestha B, Iwata M, Mera K, Sameshima H, Ohno Y, Maenosono R, Tajima Y, Uchikado H, Kuramoto T, Nakayama K, Shigemori M, Yoshida Y, Hashiguchi T, Maruyama I . MGB1: A new marker for estimation of the postmortem interval. . Experimental and Therapeutic Medicine1 ( 1 ) 109 - 111 2010.1MGB1: A new marker for estimation of the postmortem interval.Reviewed

Shrestha B*, Hashiguchi T*, Ito T*, Miura N*,(*These authors are equally contributed.) Takenouchi K, Oyama Y, Kawahara K, Tancharoen S, Ki-I Y, Arimura N, Yoshinaga N, Noma S, Shrestha C, Nitanda T, Kitajima S, Arimura K, Sato M, Sakamoto T, Maruyama I. . B cell-derived vascular endothelial growth factor a promotes lymphangiogenesis and high endothelial venule expansion in lymph nodes. . Journal of Immunology184 ( 9 ) 4819 - 4826 2010B cell-derived vascular endothelial growth factor a promotes lymphangiogenesis and high endothelial venule expansion in lymph nodes.Reviewed

Kikuchi, K., Kawahara, K., Biswas, K.K., Ito, T., Tancharoen, S., Shiomi, N., Koda, Y., Matsuda, F., Morimoto, Y., Oyama, Y., Takenouchi, K., Miura, N., Arimura, N., Nawa, Y., Arimura, S., Jie, M.X., Shrestha, B., Iwata, M., Mera, K., Sameshima, H., Ohno, Y., Maenosono, R., Tajima, Y., Uchikado, H., Kuramoto, T., Nakayama, K., Shigemori, M., Yoshida, Y., Hashiguchi, T., Maruyama, I. . HMGB1: A new marker for estimation of the postmortem interval . Experimental and Therapeutic Medicine1 ( 1 ) 109 - 111 2010Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

Estimation of the postmortem interval (PMI) is one of the most important tasks in forensic medicine Numerous methods have been proposed for the determination of the time since death by chemical means High mobility group box-1 (HMGB1), a nonhistone DNA-binding protein is released by eukaryotic cells upon necrosis Postmortem serum levels of HMGB1 of 90 male Wistar rats stored at 4 14 and 24 degrees C since death were measured by enzyme-linked immunosorbent assay The serum HMGB1 level showed a time-dependent increase up to seven days at 4 degrees C At 14 degrees C, the HMGB1 level peaked at day 3, decreased at day 4, and then plateaued At 24 degrees C, the HMGB1 level peaked at day 2, decreased at day 3, and then plateaued Our findings suggest that HMGB1 is related to the PMI in rats

DOI： 10.3892/etm_00000019

Kawaguchi Hiroaki, Miyoshi Noriaki, Fujiki Makoto, Miura Naoki, Horiuchi Masahisa, Itoh Katzuhiko, Kaneko Naoki, Miyajima Hiroaki, Nagata Ryoichi, Misumi Kazuhiro, Yasuda Nobuhiro . Microminipig atherosclerosis model by high fat and cholesterol-diet . JOURNAL OF PHARMACOLOGICAL SCIENCES112 34P 2010Reviewed International journal

Kikuchi K, Kawahara K, Biswas KK, Ito T, Tancharoen S, Morimoto Y, Matsuda F, Oyama Y, Takenouchi K, Miura N, Arimura N, Nawa Y, Meng X, Shrestha B, Arimura S, Iwata M, Mera K, Sameshima H, Ohno Y, Maenosono R, Yoshida Y, Tajima Y, Uchikado H, Kuramoto T, Nakayama K, Shigemori M, Hashiguchi T, Maruyama I. . Minocycline attenuates both OGD-induced HMGB1 release and HMGB1-induced cell death in ischemic neuronal injury in PC12 cells. . Biochem Biophys Res Commun385 ( 2 ) 132 - 136 2009.7Minocycline attenuates both OGD-induced HMGB1 release and HMGB1-induced cell death in ischemic neuronal injury in PC12 cells. Reviewed

Kikuchi K, Kawahara K, Tancharoen S, Matsuda F, Morimoto Y, Ito T, Biswas KK, Takenouchi K, Miura N, Oyama Y, Nawa Y, Arimura N, Iwata M, Tajima Y, Kuramoto T, Nakayama K, Shigemori M, Yoshida Y, Hashiguchi T, Maruyama I. . The free radical scavenger edaravone rescues rats from cerebral infarction by attenuating the release of high-mobility group box-1 in neuronal cells. . J Pharmacol Exp Ther326 ( 3 ) 865 - 874 2009.6The free radical scavenger edaravone rescues rats from cerebral infarction by attenuating the release of high-mobility group box-1 in neuronal cells.Reviewed

大川洋明（翻訳）、三浦直樹（監訳） . 猫の糖尿病 2. 病態生理，リスクファクター. . J VET、インターズー22 ( 6 ) 32 - 39 2009.6猫の糖尿病 2. 病態生理，リスクファクター.

大川洋明（翻訳）、三浦直樹（監訳） . 猫の糖尿病 1. 診断，治療，モニタリング. . J VET、インターズー22 ( 6 ) 19 - 31 2009.6猫の糖尿病 1. 診断，治療，モニタリング.

Kawahara K, Hashiguchi T, Masuda K, Saniabadi AR, Kikuchi K, Tancharoen S, Ito T, Miura N, Morimoto Y, Biswas KK, Nawa Y, Meng X, Oyama Y, Takenouchi K, Shrestha B, Sameshima H, Shimizu T, Adachi T, Adachi M, Maruyama I. . Mechanism of HMGB1 release inhibition from RAW264.7 cells by oleanolic acid in Prunus mume Sieb. et Zucc. . Int J Mol Med23 ( 5 ) 615 - 620 2009.5Mechanism of HMGB1 release inhibition from RAW264.7 cells by oleanolic acid in Prunus mume Sieb. et Zucc. Reviewed

Meng X, Kawahara K, Nawa Y, Miura N, Shrestha B, Tancharoen S, Sameshima H, Hashiguchi T, Maruyama I. . 1,5-Anhydro-D-fructose attenuates lipopolysaccharide-induced cytokine release via suppression of NF-kappaB p65 phosphorylation. . Biochem Biophys Res Commun380 ( 2 ) 343 - 348 2009.31,5-Anhydro-D-fructose attenuates lipopolysaccharide-induced cytokine release via suppression of NF-kappaB p65 phosphorylation.Reviewed

Kikuchi K, Tancharoen S, Matsuda F, Biswas KK, Ito T, Morimoto Y, Oyama Y, Takenouchi K, Miura N, Arimura N, Nawa Y, Meng X, Shrestha B, Arimura S, Iwata M, Mera K, Sameshima H, Ohno Y, Maenosono R, Tajima Y, Uchikado H, Kuramoto T, Nakayama K, Shigemori M, Yoshida Y, Hashiguchi T, Maruyama I, Kawahara KI. . Edaravone attenuates cerebral ischemic injury by suppressing aquaporin-4. . Biochem Biophys Res Commun390 ( 4 ) 1121 - 1125 2009Edaravone attenuates cerebral ischemic injury by suppressing aquaporin-4.Reviewed

Kawahara K, Hashiguchi T, Kikuchi K, Tancharoen S, Miura N, Ito T, Oyama Y, Nawa Y, Biswas KK, Meng X, Morimoto Y, Shrestha B, Sameshima H, Maruyama I. . Induction of high mobility group box 1 release from serotonin-stimulated human umbilical vein endothelial cells. . International journal of molecular medicine22 ( 5 ) 639 - 644 2008.11Induction of high mobility group box 1 release from serotonin-stimulated human umbilical vein endothelial cells.Reviewed

Kawahara, K.-i., Biswas, K.K., Unoshima, M., Ito, T., Kikuchi, K., Morimoto, Y., Iwata, M., Tancharoen, S., Oyama, Y., Takenouchi, K., Nawa, Y., Arimura, N., Jie, M.X., Shrestha, B., Miura, N., Shimizu, T., Mera, K., Arimura, S.-i., Taniguchi, N., Iwasaka, H., Takao, S., Hashiguchi, T., Maruyama, I. . C-reactive protein induces high-mobility group box-1 protein release through activation of p38MAPK in macrophage RAW264.7 cells . Cardiovascular Pathology17 ( 3 ) 129 - 138 2008Reviewed International journal

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

Background: C-reactive protein (CRP) is widely used as a sensitive biomarker for inflammation. Increasing evidence suggests that CRP plays a role in inflammation. High-mobility group box-1 (HMGB1), a primarily nuclear protein, is passively released into the extracellular milieu by necrotic or damaged cells and is actively secreted by monocytes/macrophages. Extracellular HMGB1 as a potent inflammatory mediator has stimulated immense curiosity in the field of inflammation research. However, the molecular dialogue implicated between CRP and HMGB1 in delayed inflammatory processes remains to be explored. Methods and results: The levels of HMGB1 in culture supernatants were determined by Western blot analysis and enzyme-linked immunosorbent assay in macrophage RAW264.7 cells. Purified CRP induced the release of HMGB1 in a dose- and time-dependent fashion. Immunofluorescence analysis revealed nuclear translocation of HMGB1 in response to CRP. The binding of CRP to the Fc gamma receptor in RAW264.7 cells was confirmed by fluorescence-activated cell sorter analysis. Pretreatment of cells with IgG-Fc fragment, but not IgG-Fab fragment, efficiently blocked this binding. CRP triggered the activation of p38MAPK and ERK1/2, but not Jun N-terminal kinase. Moreover, both p38MAPK inhibitor SB203580 and small interfering RNA significantly suppressed the release of HMGB1, but not the MEK1/2 inhibitor U-0126. Conclusion: We demonstrated for the first time that CRP, a prominent risk marker for inflammation including atherosclerosis, could induce the active release of HMGB1 by RAW264.7 cells through Fc gamma receptor/p38MAPK signaling pathways, thus implying that CRP plays a crucial role in the induction, amplification, and prolongation of inflammatory processes, including atherosclerotic lesions. (C) 2008 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.carpath.2007.08.006

Kawahara K, Biswas KK, Unoshima M, Ito T, Kikuchi K, Morimoto Y, Iwata M, Tancharoen S, Oyama Y, Takenouchi K, Nawa Y, Arimura N, Jie MX, Shrestha B, Miura N, Shimizu T, Mera K, Arimura S, Taniguchi N, Iwasaka H, Takao S, Hashiguchi T, Maruyama I. . CRP induces high-mobility group box-1 protein release through activation of p38MAPK in macrophage RAW264.7 cells. . Cardiovascular Pathology17 ( 3 ) 129 - 138 2007.5CRP induces high-mobility group box-1 protein release through activation of p38MAPK in macrophage RAW264.7 cells.Reviewed

Steffey MA, Miura N, Todhunter RJ, Nykamp SG, Freeman KP, Scarpino V, Vernier-Singer MA, Erb HN, MacLeod JN, Lust G, Burton-Wurster N. . The potential and limitations of cartilage-specific (V+C)- fibronectin and cartilage oligomeric matrix protein as osteoarthritis biomarkers in canine synovial fluid. . Osteoarthritis and Cartilage12 ( 10 ) 818 - 825 2004.10The potential and limitations of cartilage-specific (V+C)- fibronectin and cartilage oligomeric matrix protein as osteoarthritis biomarkers in canine synovial fluid.Reviewed

Stelley, M.A., Miura, N., Nykamp, S.G., Freeman, K.P., Scarpino, V., Vernier-Singer, M.A., Erb, H.N., Macleod, J.N., Lust, G., Burton-Wurster, N. . The potential and limitations of cartilage-specific (V + C)<sup>-</sup> fibronectin and cartilage oligomeric matrix protein as osteoarthritis biomarkers in canine synovial fluid . Osteoarthritis and Cartilage12 ( 10 ) 818 - 825 2004Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：W B SAUNDERS CO LTD

Objective: To determine if levels of the cartilage-specific (V + C)(-) fibronectin isoform in the synovial fluid is associated with cartilage change during osteoarthritis.
Design: Synovial fluid was collected from 26 healthy dogs presenting to the Orthopedic Surgery Clinic with unilateral cranial cruciate rupture, 22 control dogs, and 13 dogs from a colony maintained for the study of canine hip dysplasia. Total fibronectin, (V + C)(-) fibronectin, and cartilage oligomeric matrix protein (COMP) were quantitated by ELISA assays. Statistical analysis used Wilcoxon's signed-rank and rank-sum tests and Spearman's rank correlation.
Results: The concentration of total fibronectin was increased in affected (P < 0.0001) and contralateral (P = 0.0005) knees of the clinic population (compared to unaffected knees in colony controls). Both (V + C)(-) fibronectin and COMP concentrations were elevated in the contralateral knees in clinical patients relative to unaffected knees in the colony controls (P = 0.03 and P = 0.04, respectively), and relative to the affected knees (P = 0.003); however, corrections for joint effusions suggest elevated totals in the affected knees. (V + C)(-) fibronectin and COMP concentrations were correlated (r(sp) = 0.74; P < 0.0001) in 30 unaffected knees of patients and colony controls. Total fibronectin was correlated negatively with months since the initial injury (r(sp) = -0.44; P = 0.03) in the affected joints. The intraoperative lesion severity score did not correlate with total fibronectin or (V + C)(-) fibronectin (P greater than or equal to 0.35).
Conclusions: Concentration of total fibronectin in synovial fluid might be a useful biomarker for cross-sectional studies in osteoarthritis, but only (V + C)(-) fibronectin provides information specifically about cartilage damage. Elevated concentrations of (V + C)(-) fibronectin and COMP seen in the contralateral knees of patients with cranial cruciate rupture might indicate cartilage changes early in the disease process (pre-clinical). However, the wide range of values obtained limits the diagnostic value for any one individual. Joint effusions obscure the total amount of biomarkers in affected synovial joints. (C) 2004 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.joca.2004.07.002

Miura, N., Fujiki, M., Misumi, K., Setoyama, K., Takegawa, K., Takahashi, T., Miyahara, K., Sakamoto, H. . Successful use of an acceleration rate response pacemaker with a transvenous steroid-eluting screw-in lead for third-degree atrioventricular block in a labrador retriever . Journal of Veterinary Medical Science65 ( 10 ) 1101 - 1105 2003.10Reviewed International journal

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

Permanent pacemakers are commonly used in veterinary practice and can have a dramatic effect on the treatment of heart block. A Labrador Retriever dog suffering from exercise intolerance secondary to third degree atrioventricular block was treated with a new pacemaker system. A steroid-eluting screw-in type lead that has the advantage of being more fixed to the myocardial wall without increasing the pacing threshold was used. The heart rate was regulated with an acceleration sensing pacemaker generator that included several automatic modulation systems. Nineteen months after implantation, the dog has a normal level of activity. The present case suggests that this pacemaker design may offer important advantages for canine patients.

DOI： 10.1292/jvms.65.1101

Miura N, Fujiki M, Misumi K, Setoyama K, Takegawa K, Takahashi T, Miyahara K, Sakamoto H. . Successful use of an acceleration rate response pacemaker with a transvenous steroid-eluting screw-in lead for third-degree atrioventricular block in a labrador retriever. . J Vet Med Sci65 ( 10 ) 1101 - 1105 2003.10Successful use of an acceleration rate response pacemaker with a transvenous steroid-eluting screw-in lead for third-degree atrioventricular block in a labrador retriever.Reviewed

三浦直樹, 藤木誠, 三角一浩, 瀬戸山健太郎, 竹川和明, 高橋健, 宮原健吉, 坂本紘 . 第三度の房室ブロックのラブラドールレトリバーに対するAcceleration Rate Response制御型ペースメーカと経静脈Steroid-eluting Screw-in型リードを用いた治検例(短報)(Successful Use of an Acceleration Rate Response Pacemaker with a Transvenous Steroid-Eluting Screw-in Lead for Third-Degree Atrioventricular Block in a Labrador Retriever) . The Journal of Veterinary Medical Science65 ( 10 ) 1101 - 1105 2003.10第三度の房室ブロックのラブラドールレトリバーに対するAcceleration Rate Response制御型ペースメーカと経静脈Steroid-eluting Screw-in型リードを用いた治検例(短報)(Successful Use of an Acceleration Rate Response Pacemaker with a Transvenous Steroid-Eluting Screw-in Lead for Third-Degree Atrioventricular Block in a Labrador Retriever)Reviewed International journal

Amano T, Yamasaki S, Yagishita N, Tsuchimochi K, Shin H, Kawahara K, Aratani S, Fujita H, Zhang L, Ikeda R, Fujii R, Miura N, Komiya S, Nishioka K, Maruyama I, Fukamizu A, Nakajima T. . Synoviolin/Hrd1, an E3 ubiquitin ligase, as a novel pathogenic factor for arthropathy. . Genes Dev17 ( 19 ) 2436 - 2449 2003.7Synoviolin/Hrd1, an E3 ubiquitin ligase, as a novel pathogenic factor for arthropathy.Reviewed

Kamimura R, Miura N, Suzuki S. . The hemodynamic effects of acute myocardial ischemia and reperfusion in Clawn miniature pigs. . Exp Anim52 ( 4 ) 335 - 338 2003.7The hemodynamic effects of acute myocardial ischemia and reperfusion in Clawn miniature pigs.Reviewed

上村亮三, 三浦直樹, 鈴木秀作 . Clawnミニブタを用いた急性心筋虚血及び再灌流時の血行動態(The Hemodynamic Effects of Acute Myocardial Ischemia and Reperfusion in Clawn Miniature Pigs) . Experimental Animals52 ( 4 ) 335 - 338 2003.6Clawnミニブタを用いた急性心筋虚血及び再灌流時の血行動態(The Hemodynamic Effects of Acute Myocardial Ischemia and Reperfusion in Clawn Miniature Pigs)Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：(公社)日本実験動物学会

Clawnミニブタに心筋虚血を作製した.連続虚血群の3/8例が虚血後20分以内に,虚血再灌流群の4/9例が再灌流後に不整脈で死亡した.虚血領域は再灌流群の方が狭かった.再灌流障害は血行動態に重大な影響を与えることが示唆された

Miura N, Fujiki M, Miyoshi Y, Misumi K, Sakamoto H. . Steroid injection therapy in a feline solitary bone cyst. . J. Vet. Med. Sci65 ( 4 ) 523 - 525 2003.4Steroid injection therapy in a feline solitary bone cyst.Reviewed

三浦直樹, 藤木誠, 三好宣彰, 三角一浩, 坂本紘 . ステロイド局所注入療法を行った猫の単発性骨嚢胞(Solitary Bone Cyst)の一例(Steroid Injection Therapy in a Feline Solitary Bone Cyst) . The Journal of Veterinary Medical Science65 ( 4 ) 523 - 525 2003.4ステロイド局所注入療法を行った猫の単発性骨嚢胞(Solitary Bone Cyst)の一例(Steroid Injection Therapy in a Feline Solitary Bone Cyst)Reviewed International journal

Setoyama K, Ota H, Miura N, Fujiki M, Misumi K, Sakamoto H. . Effects of milrinone on hemodynamics and regional blood flow in the hypoxic dog. . J. Vet. Med. Sci.64 ( 6 ) 499 - 503 2002.6Effects of milrinone on hemodynamics and regional blood flow in the hypoxic dog. Reviewed

瀬戸山健太郎, 大田宏美, 三浦直樹, 藤木誠, 三角一浩, 坂本紘 . 低酸素下の犬におけるミルリノンの血行動態ならびに臓器血流に及ぼす影響(Effects of Milrinone on Hemodynamics and Regional Blood Flow in the Hypoxic Dog) . The Journal of Veterinary Medical Science64 ( 6 ) 499 - 503 2002.6低酸素下の犬におけるミルリノンの血行動態ならびに臓器血流に及ぼす影響(Effects of Milrinone on Hemodynamics and Regional Blood Flow in the Hypoxic Dog)Reviewed International journal

Kawabata H, Kawahara K, Kanekura T, Araya N, Daitoku H, Hatta M, Miura N, Fukamizu A, Kanzaki T, Maruyama I, Nakajima T. . Possible role of transcriptional coactivator P/CAF and nuclear acetylation in calcium-induced keratinocyte differentiation. . J. Biol. Chem.277 ( 10 ) 8099 - 8105 2002.3Possible role of transcriptional coactivator P/CAF and nuclear acetylation in calcium-induced keratinocyte differentiation.Reviewed

MISUMI Kazuhiro, TORII Tetsutaroh, AOKI Osamu, FUJIKI Makoto, MIURA Naoki, YANAGITA Kohichi, SAKAMOTO Hiroshi . Effects of Trimming on Hoof Growth, Hoof-disease Occurrence, and Productivity in Japanese Black Beef Cattle . Journal of the Japan Veterinary Medical Association54 ( 11 ) 829 - 836 2001.11Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：Japan Veterinary Medical Association

This study was designed to determine effects of trimming on hoof growth, hoof-disease occurrence, and beef productivity. Sixteen Japanese black steers (13.0±2.0 months of age, 308.0±30.8 kg in body weight) were divided into 4 groups: the no-trimming group and group 2; in which trimming was performed at 3-month intervals; group 3, in which trimming was performed at 6-month intervals; and group 4, in which trimming was performed at 12month-intervals. At 19-month intervals, hooves were measured and hoof appearance recorded.After slaughter, we made pathological investigations of hoof and joint diseases and obtained scores representing the quantity and quality of beef products. When trimming intervals were longer, hoof angle was smaller, and hoof wall and bulb height increased. The occurrence of hoof diseases in the no-trimming group was significantly higher (P<0.05) than in the other groups. Scores for beef-product quantity were significantly higher (P<0.05) in group 3, in which trimming was performed at 6-month intervals, than in the other groups. These results suggest that trimming may be useful in maintaining normal hoof growth and preventing deformation and disease.

DOI： 10.12935/jvma1951.54.829

MISUMI Kazuhiro, SHINSATO Takeshi, AOKI Osamu, SETOYAMA kentaroh, MIURA Naoki, YANAGITA Kohichi, SAKAMOTO Hiroshi . Effects of Hoof Trimming on Hematological and Biochemical Variables during Transport-induced Stress in Japanese Black Cattle . Journal of the Japan Veterinary Medical Association54 ( 11 ) 837 - 840 2001.11Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：Japan Veterinary Medical Association

The purpose of this study is to determine effects of hoof trimming on transport-induced stress in beef cattle. Forty-one Japanese black steers were randomly divided into 2 groups: trimmed group (n=27) and untrimmed group (n=14). In the trimmed group, hoof trimming was repeated every 6 months, with the final trimming performed 3 months before shipment. The untrimmed group was not trimmed at all until shipment time. Before and after truck transportation to the shipping destination (57.8 km, 4 hours), the cattle were weighed, and their blood was sampled for hematological and biochemical analysis. The indices of transport-induced stress were creatine phosphokinase (CK) and cortisol. In both groups, CK and cortisolincreased after transportation. Increase in the parameters was lower in the trimmed group than in the untrimmed group. Lower CK activity in the trimmed group suggests that the physical demand for posture support during transport in the vehicle was more restricted in thetrimmed group. Plasma cortisol increased less in the trimmed group than in the untrimmed group. This could mean that periodical trimming effectively inhibits transport-induced stress in beef cattle.

DOI： 10.12935/jvma1951.54.837

三角一浩, 鳥居哲太郎, 青木修, 藤木誠, 三浦直樹, 柳田宏一, 坂本紘 . 削蹄による肥育用黒毛和種牛の蹄形,蹄病発生及び生産性の変化 . 日本獣医師会雑誌54 ( 11 ) 829 - 836 2001.11削蹄による肥育用黒毛和種牛の蹄形,蹄病発生及び生産性の変化Reviewed International journal

三角一浩, 新里健, 青木修, 瀬戸山健太郎, 三浦直樹, 柳田宏一, 坂本紘 . 肉用牛の輸送ストレスに対する削蹄の効果 . 日本獣医師会雑誌54 ( 11 ) 837 - 840 2001.11肉用牛の輸送ストレスに対する削蹄の効果Reviewed International journal

FUJIKI Makoto, MIURA Naoki, MISUMI Kazuhiro, TSURUTA Tsutomu, SAKAMOTO Hiroshi . A Case of Canine Cricopharyngeal Achalasia . Journal of the Japan Veterinary Medical Association54 ( 9 ) 697 - 700 2001.9Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：Japan Veterinary Medical Association

A three-year-old, female Shih Tzu with a history of dysphagia persisting since weaning had been kept on a liquid diet for about two years. The dog was referred to us because of difficulty in swallowing liquid food. Clinical signs, radiographic findings, and fluoroscopic examination after ingestion of food mixed with barium confirmed a diagnosis of cricopharyngeal achalasia. Four days later, we performed cricopharyngeal myotomy. After surgery, the dog no longer had difficulty swallowing food and was discharged on the third postoperative day. The dog has been clinically normal for 17 months.

DOI： 10.12935/jvma1951.54.697

藤木誠, 三浦直樹, 三角一浩, 鶴田勉, 坂本紘 . 犬の輪状咽頭筋アカラジアの1例 . 日本獣医師会雑誌54 ( 9 ) 697 - 700 2001.9犬の輪状咽頭筋アカラジアの1例Reviewed International journal

MIURA Naoki, SUZUKI Syusaku, HAMADA Yuji, KAMIMURA Ryozo, UMEMOTO Chiyoshi, FUJIKI Makoto, MISUMI Kazuhiro, SAKAMOTO Hirosi . Effects of Exposure to Alternating-current, High-voltage, Electric Potential on Experimental Hypertension in Dahl-S Rats . Journal of the Japan Veterinary Medical Association54 ( 6 ) 472 - 475 2001.6Reviewed International journal

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Japan Veterinary Medical Association

Antihypertensive effect of exposure alternating current, high-voltage, electrical potential (AC-HVEP) were investigated in Dahl salt-sensitive (Dahl-S) rats used as models of salt-induced hypertension. The animals were divided into two groups: rats exposure to AC-HVEP (AC-HVEP group) and a control group not exposed to AC-HVEP. Throughout the experimental period, water with an addition of 1.0% NaC1 was given the animals. Progressive hypertension in the AC-HVEP group was significantly less serious than in the control group. In addition, histopathological examination showed greater restriction of lesions in the AC-HVEP than in the control group. Our results suggest that AC-HVEP exposure can suppress progressive hypertension secondary to chronic renal failure.

DOI： 10.12935/jvma1951.54.472

三浦直樹、鈴木秀作、浜田佑二、上村亮三、梅本千代志、藤木誠、三角一浩、坂本紘 . 交流高圧電位負荷の高血圧モデル動物に対する高血圧抑制効果. . 日獣会誌54 ( 6 ) 472 - 475 2001.6 交流高圧電位負荷の高血圧モデル動物に対する高血圧抑制効果.Reviewed

上村亮三, 鈴木秀作, 三浦直樹, 宮原健吉 . コレステロール投与New Zealand Whiteウサギの肺動脈硬化症と肺動脈圧(Pulmonary Atherosclerosis and Pulmonary Arterial Pressure in Cholesterol-Fed New Zealand White Rabbits) . The Journal of Veterinary Medical Science63 ( 6 ) 647 - 653 2001.6コレステロール投与New Zealand Whiteウサギの肺動脈硬化症と肺動脈圧(Pulmonary Atherosclerosis and Pulmonary Arterial Pressure in Cholesterol-Fed New Zealand White Rabbits)Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：(公社)日本獣医学会

実験を3群に分け,コントロール群にはウサギ用標準飼料を8週間,コレステロール投与群には標準飼料に0.5%コレステロール及び0.25%胆汁酸を添加した高コレステロール飼料を8週間(実験群1)と15週間(実験群2),1日90g/例ずつ投与した.肺動脈圧は,収縮期,拡張期共に,実験群2が最も高く,次に実験群1,コントロール群の順であった.3群間に大きな差は認められなかったが,平均肺動脈圧のコントロール群と実験群2の間に統計学的有意差が認められた.組織学的には実験群1の肺動脈は幹気管支〜細気管支レベルの肺動脈を中心に,血管内皮下に軽度の限局性の泡沫細胞集簇が認められた.実験群2では細気管支レベルの肺動脈を中心に泡沫細胞の集簇により,中等度〜高度の血管内腔狭窄像が観察され,増殖細胞の一部は中膜から外膜に達していた.しかしながら,肺全体では高度病変は部分的には認められるものの,軽度病変が主体であった.今回の結果からコレステロール投与ウサギの肺動脈にも泡沫細胞増殖を主体とする動脈硬化病変が観察され,内膜肥厚及び血管内腔の高度狭窄も認められた.一方,肺高血圧を呈する程ではなかったものの,肺動脈圧は経時的に漸増した

K Misumi, O Tateno, M Fujiki, N Miura, H Sakamoto . The risk of contrast media-induced ventricular fibrillation is low in canine coronary arteriography with ioxilan . JOURNAL OF VETERINARY MEDICAL SCIENCE62 ( 4 ) 421 - 426 2000.4Reviewed International journal

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

Previous studies have proposed that sodium supplement to nonionic contrast media (CM) can decrease the risk of ventricular fibrillation (VF). This study was designed to compare the occurence of VF induced by ioxilan (containing 9 mmol/LNa+) with other nonionic CMs. After wedging a catheter in the right coronary artery, test solutions including ioxilan, ioversol, iomeprol, and iopromide were infused for 30 sec at the rate of 0.4 ml/sec or until VF occurred. Then, incidence of VF, contact time (i.e. the time required to produce VF), and QTc were measured. Also, the CMs other than ioxilan were investigated at sodium levels adjusted to 9 and 20 mmol/L Na+. The incidence of VF with ioxilan (0%) was the lowest of all. In the other CMs, the incidence decreased in accordance with increase of sodium. Iomeprol and iopromide showed significant reduction of VF incidence at the sodium level of 20 mmol/L. The higher sodium supplements also prolonged the contact times. The increase of QTc was the greatest in ioxilan. Ioxilan has the least arrythmogenic property among the current low-osmolality nonionic CMs. This property might be attributable to an optimal sodium concentration of 9 mmol/L in the CM.

DOI： 10.1292/jvms.62.421

HIRAKAWA Atsushi, FUJIKI Makoto, MIURA Naoki, SHIBAYAMA Hinako, TAKAHASHI Yoshiaki, OMICHI Yoshihiro, NOGUCHI Kayo, YAMAMOTO Masaaki, SAKAMOTO Hiroshi . Pacemaker Implantation in a Cat with Paroxysmal Third-degree Atrioventricular Block . Journal of the Japan Veterinary Medical Association53 ( 2 ) 75 - 79 2000.2Reviewed International journal

平川篤, 藤木誠, 三浦直樹, 柴山比奈子, 高橋義明, 大道嘉広, 野口佳代, 山本昌章, 坂本紘 . 発作性第3度房室ブロックに対しペースメーカーの植え込みを実施した猫の1例 . 日本獣医師会雑誌53 ( 2 ) 75 - 79 2000.2発作性第3度房室ブロックに対しペースメーカーの植え込みを実施した猫の1例Reviewed International journal

HIRAKAWA Atsushi, FUJIKI Makoto, MIURA Naoki, SHIBAYAMA Hinako, TAKAHASHI Yoshiaki, OMICHI Yoshihiro, NOGUCHI Kayo, YAMAMOTO Masaaki, SAKAMOTO Hiroshi . Pacemaker Implantation in a Cat with Paroxysmal Third-degree Atrioventricular Block . Journal of the Japan Veterinary Medical Association53 ( 2 ) 75 - 79 2000Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：Japan Veterinary Medical Association

A male mongrel cat (age 8 years and 5 months) was referred to our clinic because of syncopal episodes. Electrocardiography revealed paroxysmal third-degree atrioventricular block. Because syncopal episodes became increasingly frequent over a period of 5 months, permanent pacemaker implantion was performed. One year after the operation, no further syncopes had occurred. To the best of our knowledge, this is the first report in Japan of long-term observation of pacemaker implantation in a cat.

DOI： 10.12935/jvma1951.53.75

Kakura, H., Miyahara, K., Amitani, S., Sohara, H., Koga, M., Sakamoto, H., Misumi, K., Miura, N. . Hemodynamic effects of intravenous administration of olprinone hydrochloride on experimental pulmonary hypertension . Arzneimittel-Forschung/Drug Research50 ( 6 ) 515 - 519 2000Reviewed International journal

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

To examine acute effects of olprinone hydrochloride (CAS 1067302-54-0, Coretec®) on pulmonary hypertension, hypoxic pulmonary hypertension was produced in 6 adult Beagle dogs. Using this pulmonary hypertension model, single intravenous bolus injections of olprinone at doses of 10, 30 and 100 μg/kg were administered at 5-min intervals and hemodynamic parameters were evaluated. Heart rate increased at doses of 30 and 100 μg/kg, but did not change at a dose of 10 μg/kg. Mean aortic pressure, mean pulmonary arterial pressure, pulmonary vascular resistance and systemic vascular resistance and right ventricular stroke work index did not change at doses of 10 and 30 μg/kg, but they decreased significantly at a dose of 100 μg/kg. On the other hand, cardiac index and the first derivative value of the left ventricular pressure did not show significant change at all doses. These results indicate the vasodilating effects on peripheral and pulmonary vessels in hypoxic model at high doses of olprinone. Its application in right heart failure accompanied by pulmonary hypertension therefore is expected to yield promising results.

DOI： 10.1055/s-0031-1300240

Misumi, K., Fujiki, M., Miura, N., Sakamoto, H. . Uterine horn torsion in two non-gravid bitches . Journal of Small Animal Practice41 ( 10 ) 468 - 471 2000Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：BRITISH VETERINARY ASSOC

Uterine torsion secondary to sacculation of the uterine horns was diagnosed in two non-gravid bitches which were presented with anorexia, polydipsia and an acutely swollen abdomen, On the basis of the radiological and ultrasonographic findings, which indicated the presence of an enlarged spherical or tubular structure filled with hypoechoic material in the caudal abdomen, a tentative diagnosis of pyometra was made. Exploratory laparotomy revealed unilateral uterine horn torsion along the longitudinal axis, with bilateral fluid-filled sacculations. Ovariohysterectomy was performed in both cases. Pathological examination of the uteri demonstrated haematometra in one dog and pyometra in the other.

DOI： 10.1111/j.1748-5827.2000.tb03144.x

Miura N, Suzuki S, Hamada Y, Kamimura R, Fujiki M, Misumi K, Sakamoto H. . Salt water promotes hypertension in Dahl-S rats. . Exp. Anim48 ( 4 ) 289 - 292 1999.10Salt water promotes hypertension in Dahl-S rats.Reviewed

三浦直樹, 鈴木秀作, 浜田佑二, 上村亮三, 藤木誠, 三角一浩, 坂本紘 . 食塩水投与によるDahl-S-Ratの高血圧症の作成 . Experimental Animals48 ( 4 ) 289 - 292 1999.10食塩水投与によるDahl-S-Ratの高血圧症の作成Reviewed International journal

Kamimura, R., Suzuki, S., Sakamoto, H., Miura, N., Misumi, K., Miyahara, K. . Development of atherosclerotic lesions in cholesterol-loaded rabbits . Experimental Animals48 ( 1 ) 1 - 7 1999.1Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：INT PRESS EDITING CENTRE INC

To examine both of the target vessels and the optimal time of their endothelial denudation to study vascular restenosis after balloon injury in cholesterol-loaded rabbits, we made 36 atherosclerotic rabbits by feeding a hypercholesterol diet, and histologically examined the onset time and the development of atherosclerosis. Atheromatous changes were observed first after the 5th week in the thoracic aorta from the start of the diet, and then extended to the abdominal aorta, coronary artery with time. The atherosclerotic lesions in the thoracic aorta and the proximal portion of the coronary artery showed high-grade concentric intimal thickening with luminal stenosis. The abdominal aortic lesion mildly progressed. In the renal, carotid and femoral arteries, in contrast, slight atheroscleromatous changes developed during the diet period. These results suggest that the thoracic and abdominal aortas and the coronary artery would be suitable as target vessels to study vascular restenosis after balloon injury, and the endothelial denudation of these vessels should be performed between the 8th and 15th week in this diet protocol for an accurate analysis.

DOI： 10.1538/expanim.48.1

上村亮三, 鈴木秀作, 坂本紘, 三浦直樹, 三角一浩, 宮原健吉 . コレステロール負荷ウサギにおける動脈硬化病変の進展 . Experimental Animals48 ( 1 ) 1 - 7 1999.1コレステロール負荷ウサギにおける動脈硬化病変の進展Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：(公社)日本実験動物学会

36例のNZWウサギに0.5%コレステロール含有飼料を4〜15週間投与し,病変形成時期と進展経過について組織学的に検索した.病変形成時期は胸大動脈が投与5週目,腹大動脈が6週目,冠動脈が7週目,腎・総頸・大腿動脈が8週目と部位によって大きな差が認められた.胸大動脈・冠動脈の病変は経時的に進展し,中等度〜高度の内腔狭窄も認められたが,腹大動脈病変の進展経過は比較的緩やかであった.腎・総頸・大腿動脈の病変進展は極めて緩徐で,15週目でも局所病変にとどまった.この実験結果から,動脈硬化病変を有する血管を用いたballoon傷害後のrestenosisに関する研究では,cholesterol投与15週迄のモデルでも,胸大動脈・冠動脈・腹大動脈が対象血管となり得,それらの内皮剥離の至適時期は投与後8〜15週の間であることが推察された

Amitani, S., Miyahara, K., Sohara, H., Kakura, H., Koga, M., Moriyama, Y., Taira, A., Nagano, S.-I., Miura, N., Misumi, K., Sakamoto, H. . Experimental His-bundle pacing: Histopathological and electrophysiological examination . PACE - Pacing and Clinical Electrophysiology22 ( 4 I ) 562 - 566 1999Reviewed International journal

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

His-bundle pacing gives a more physiological ventricular contraction in comparison to right ventricular apical pacing. However the problems of lead fixation and stability of long-term His-bundle pacing are yet unsolved. We used six adult beagles, in which a screw-in lead was anchored in the His- bundle region for observation of the pacing conditions and histopathologic changes of the conduction system over the course of 2 months. In the results, a satisfactory fixation was obtained using a conventional screw-in lead and no histological influence on the conduction system was observed. The pacing threshold at the time of implantation was 1.15 ± 0.69V (3.23 ± 3.08 mA) in the pulse width of 0.5 ms. R wave amplitude, the impedance and slew rate were 7.28 ± 2.04 mV, 409 ± 102 Ohm, and 0.65 ± 0.41 V/s, respectively. Two months later, these parameters changed to 2.83 ± 1.06 V (10.4 ± 5.71 mA), 5.63 ± 1.62 mV, 310 ± 71.3 Ohm, and 0.49 ± 0.22 V/s, respectively. These results suggest the feasibility of clinical application of permanent His- bundle pacing.

DOI： 10.1111/j.1540-8159.1999.tb00497.x

藤木誠, 三浦直樹, 三角一浩, 坂本絋 . 麻酔モニター(BP-508)の終末呼気二酸化炭素分圧と平均動脈圧に対するイヌでの有効性 . 獣医麻酔外科学雑誌 = Japanese journal of veterinary anesthesia & surgery29 55 1998.10Reviewed International journal

KAMIMURA Shunichi, HASHINOKUCHI Tetsu, USHINOHAMA Kanji, MIURA Naoki, HAMANA Katsumi, SAKAMOTO Hiroshi . A Clinical Case of Bladder Rupture Occurring in a New-Born Japanese Black Calf . Journal of the Japan Veterinary Medical Association51 ( 5 ) 246 - 248 1998.5Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：Japan Veterinary Medical Association

A 15-day-old female calf complaining urinary obstruction and hematuria, was diagnosed as bladder rupture by positive-contrast cystography and ultrasonography. Through a posterior ventral midline incision one third of bladder containing ruptured devitalized tissue was debrided, resulting in recovery after operation. The case was suspected to be due to urachal anomaly type 2, a vesicourachal diverticulum.

DOI： 10.12935/jvma1951.51.246

Sakamoto, H., Kirihara, H., Fujiki, M., Miura, N., Misumi, K. . The Effects of Medetomidine on Maternal and Fetal Cardiovascular and Pulmonary Function, Intrauterine Pressure and Uterine Blood Flow in Pregnant Goats . Experimental Animals46 ( 1 ) 67 - 73 1997.1Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：International Press Editing Centre Incorporation

To investigate the effects of medetomidine on late pregnant goats, medetomidine induced changes in maternal or fetal circulation and acid-base balance, as well as changes in intrauterine pressure (IUP) and uterine blood flow (UBF), were studied. Intramuscular administration of medetomidine (40 μg/kg b.w.) decreased the heart rate (HR) and arterial blood pressure (ABP) of the mother, and the change in HR was significant statistically (p&lt
0.05). In the fetus, HR and ABP showed a transient decrease and increase (p&lt
0.05), respectively. A decrease in maternal arterial blood pH and oxygen partial pressure (PO2) and an increase in carbon dioxide partial pressure (PCO2) were recorded alter the injection, but none was significant. In the fetus, arterial blood PO2 decreased significantly (p&lt
0.05) after 5 min of administration, and a significant metabolic acidemia supported by a decrease in base excess was observed. Within 1 to 4 min after the administration of medetomidine, IUP began to rise and remained high for 10 to 14 min. Thereafter, the rise in IUP was frequent and periodical. After the injection, UBF significantly (p&lt
0.05) decreased, and the fall in UBF was associated with a rise in IUP. The maternal and fetal serum medetomidine concentration increased remarkably after the injection of medetomidine into the mother. These observations in late pregnant goats suggested that medetomidine induced a decrease in maternal cardiac output, a decrease in UBF arising from the induction of uterine contractions, and transplacental medetomidine can have a suppressive effect on the fetus.

DOI： 10.1538/expanim.46.67

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