研究者データベース

永田 矩之(ナガタ ノリユキ)
獣医学研究院 附属動物病院
特任助教

基本情報

所属

  • 獣医学研究院 附属動物病院

職名

  • 特任助教

学位

  • 学士(獣医学)(大阪府立大学)

科研費研究者番号

  • 80897786

ORCID ID

J-Global ID

研究キーワード

  • 臨床獣医学   

研究分野

  • ライフサイエンス / 獣医学

職歴

  • 2020年10月 - 現在 北海道大学大学院 附属動物病院 特任助教
  • 2018年04月 - 2020年09月 北海道大学大学院 獣医学研究科 日本学術振興会特別研究員DC1
  • 2010年04月 - 2016年03月 湯木どうぶつ病院 獣医師

所属学協会

  • 日本獣医師会   

研究活動情報

論文

  • Jumpei Yamazaki, Shinji Meagawa, Jaroslav Jelinek, Shoko Yokoyama, Noriyuki Nagata, Masashi Yuki, Mitsuyoshi Takiguchi
    Research in veterinary science 139 193 - 199 2021年10月 [査読有り]
     
    Obesity and its associated comorbidities constitute a major and growing health problem worldwide not only involved with people but also dogs and cats. Although few genetic mutations have been associated with obesity in dogs, molecular mechanism remains to be clearly understood. Given the fact that DNA methylation leads to gene expression variability and has plasticity affected by metabolic phenotypes such as obesity in human, the objective of this study is to identify obesity-associated differentially methylated cytosine-phosphate-guanine (CpG) dinucleotide sites in dogs. With genome-wide DNA methylation analysis using next-generation sequencing for blood samples from fourteen Miniature dachshunds with body condition score (BCS) 4-5 and BCS ≥6, over 100,000 sites could be analysed to identify genomic locations of differentially methylated CpG sites. As a result, 191 differentially methylated CpG sites (89 CpG sites were hypermethylated in BCS ≥6 and 102 were hypermethylated in BCS 4-5) were identified. These sites included promoter regions of Kisspeptin receptor (KISS1R) and Calcyphosine 2 (CAPS2) genes which were subsequently validated by bisulfite-pyrosequencing for another set of 157 dog blood samples. KISS1R methylation levels were found to be higher in BCS ≥6 group than BCS 4-5 in senior (>84 months) dogs. Especially male dogs but not female dogs as well as uncastrated male dogs but not castrated male dogs showed this trend. DNA methylation of KISS1R gene will be useful for understanding of comprehensive epigenetic change in obese dogs.
  • Noboru Sasaki, Thandar Oo, Yoshikazu Yasuda, Takahiro Ichise, Noriyuki Nagata, Nozomu Yokoyama, Kazuyoshi Sasaoka, Keitaro Morishita, Shouta Mm Nakayama, Mayumi Ishizuka, Kensuke Nakamura, Mitsuyoshi Takiguchi, Yoshinori Ikenaka
    The Journal of veterinary medical science 2021年09月17日 [査読有り]
     
    We developed an analytical method using an on-line column-switching liquid chromatography with triple quadrupole mass spectrometry (LC/MS/MS) for quantifying multiple steroids in serum. Using the developed method, we evaluated the serum concentration of nine steroids (cortisol, corticosterone, cortisone, 11-deoxycortisol, 21-deoxycortisol, deoxycorticosterone, progesterone, 17α-OH-progesterone and aldosterone) in dogs with hyperadrenocorticism (HAC). Serum was mixed with stable isotope internal standards and thereafter purified by the automated column-switching system. The limit of detection ranged 2-16 pg/ml for nine steroids. In the baseline samples, five steroids (cortisol, corticosterone, cortisone, 11-deoxycortisol, and 17α-OH-progesterone) were detected in all dogs. The concentrations of cortisone, 11-deoxycortisol, and 17α-OH-progesterone in dogs with HAC (n=19) were significantly higher those in dogs without HAC (n=15, P<0.02). After the adrenocorticotropic hormone stimulation test, six steroids (cortisol, corticosterone, cortisone, 11-deoxycortisol, 17α-OH-progesterone, and deoxycorticosterone) were above the limit of quantification in all dogs. Cortisol, corticosterone, cortisone, and deoxycorticosterone concentrations of dogs with HAC were significantly higher than those of dogs without HAC (P<0.02). In addition, 11-deoxycortisol and 17α-OH-progesterone concentration was higher in dogs with HAC than in dogs without HAC (P=0.044 and P=0.048, respectively). The on-line column-switching LC/MS/MS would be feasible for measuring multiple steroids in dog serum. The results suggest that cortisone, 11-deoxycortisol, and 17α-OH-progesterone would be related to HAC. Further studies are warranted to assess the clinical feasibility of steroid profile in dogs with HAC.
  • Kevin Christian Montecillo Gulay, Noriyuki Nagata, Keisuke Aoshima, Nozomi Shiohara, Atsushi Kobayashi, Mitsuyoshi Takiguchi, Takashi Kimura
    Journal of comparative pathology 187 63 - 67 2021年08月 [査読有り]
     
    A 6-year-old spayed female Toy Poodle dog was referred to the Hokkaido University Veterinary Teaching Hospital for abdominal distension. Abdominocentesis yielded ascitic fluid that had a mildly increased total protein concentration and a 2.7-fold higher triglyceride concentration than plasma, and was interpreted as chylous ascites. The patient had an enlarged liver, which contained multiple, small, nodular masses and cyst-like structures. Microscopically, these lesions were multifocal dilated spaces containing lymphocytes, endothelial cells, fibrin and islands of hepatocytes. Increased α-smooth muscle actin-positive cells were observed in hepatic sinusoids. Based on these findings, we diagnosed peliosis hepatis with chylous ascites, which is likely to have been due to lymphangiectasia and disrupted hepatic sinusoids. Neither Bartonella spp DNA nor mutations in ACVRL1 and MTM1 genes were detected, although there was a 47-fold increase in hepatic ACVRL1 expression compared with age-matched control liver. To the authors' knowledge, this is the first report of chylous ascites resulting from peliosis hepatis in any species.
  • Noboru Sasaki, Yoshinori Ikenaka, Yumiko Inoue, Takahiro Ichise, Noriyuki Nagata, Mayumi Ishizuka, Syouta Mm Nakayama, Kensuke Nakamura, Mitsuyoshi Takiguchi
    The Journal of veterinary medical science 83 4 648 - 655 2021年04月09日 [査読有り]
     
    Measurement of urinary metanephrines in spot samples is used for the diagnosis of canine pheochromocytoma (PC). We describe a simple analytical method based on liquid chromatography tandem mass spectrometry (LC-MS/MS) for measuring free metanephrine (MN) and normetanephrine (NMN) in spot urine samples. Using the developed method, we evaluated the stability of urinary free-MN and free-NMN at various storing conditions. In addition, we assessed the feasibility of urinary free-MN and -NMN measurement for diagnosing PC. Urine samples were mixed with stable isotope internal standards and thereafter purified by ultrafiltration. The purified samples were analyzed by LC-MS/MS in the multiple reaction monitoring mode after separation on a multimode octa decyl silyl column. The coefficient of variation of free-MN and -NMN measurement was 7.6% and 5.5%, respectively. The linearity range was 0.5-10 µg/l for both analytes. Degradation was less than 10% for both analytes under any of the storage conditions. The median free-NMN ratio to creatinine of 9 PC dogs (595, range 144-47,961) was significantly higher (P<0.05) than that of 13 dogs with hypercortisolism (125, range 52-224) or 15 healthy dogs (85, range 50-117). The developed method is simple and may not require acidification of spot urine. The results of this preliminary retrospective study suggest that the measurement of urinary free metanephrines is a promising tool for diagnosing canine PC.
  • Hiroshi Ohta, Noriyuki Nagata, Nozomu Yokoyama, Tatsuyuki Osuga, Noboru Sasaki, Keitaro Morishita, Mitsuyoshi Takiguchi
    The Journal of veterinary medical science 83 3 378 - 384 2021年03月11日 [査読有り]
     
    To date, little is known about the prognostic significance of ultrasonographic findings in dogs with protein-losing enteropathy (PLE). The aim of this retrospective study was to examine the prognostic value of ultrasonographic findings in dogs with PLE. A total of 26 dogs with PLE were included: 20 dogs with chronic enteropathy and 6 dogs with gastrointestinal lymphoma. The presence of small intestinal dilatation was associated with shorter survival time in dogs with PLE (P=0.003). The presence of hyperechoic intestinal mucosal striations was associated with longer survival time in dogs with PLE (P=0.0085). The results of the current study indicate that the presence of small intestinal dilatation might be associated with poor prognosis in dogs with PLE.
  • Hiroshi Ohta, Yu Tamura, Nozomu Yokoyama, Noriyuki Nagata, Tatsuyuki Osuga, Noboru Sasaki, Yumiko Kagawa, Keitaro Morishita, Mitsuyoshi Takiguchi
    The Journal of veterinary medical science 82 10 1445 - 1449 2020年10月20日 [査読有り]
     
    Inflammatory colorectal polyps (ICRPs) in miniature dachshunds (MDs) are speculated to be a breed-specific inflammatory bowel disease (IBD). Leucine-rich alpha-2 glycoprotein (LRG) has been identified as a novel biomarker of human IBD. The aim of this study was to examine LRG gene expression in the polypoid lesions of ICRPs. Polypoid lesion specimens were collected from 24 MDs with ICRPs. Nonpolypoid colonic mucosa was collected from 18 MDs with ICRPs and 10 controls. The gene expression of LRG, interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and IL-22 was examined. The expression of LRG gene was significantly increased in the polypoid lesions of ICRPs and correlated with that of the four cytokines. In conclusion, the LRG gene was expressed within the polypoid lesions of ICRPs and might be associated with local cytokine expression.
  • Noboru Sasaki, Noriyuki Nagata, Keitaro Morishita, Tatsuyuki Osuga, Kazuyoshi Sasaoka, Nozomu Yokoyama, Hiroshi Ohta, Mitsuyoshi Takiguchi
    The Journal of veterinary medical science 82 7 1012 - 1016 2020年07月31日 [査読有り]
     
    The feasibility of ultrasonographic measurement of thyroid gland area to common carotid artery (TG:CCA) was investigated. Twenty-one healthy, 12 hypothyroid and 18 non-thyroid illness (NTI) dogs were evaluated. The area of thyroid lobe and common carotid artery in right and left sides were measured using the same ultrasonographic images in transverse plane. The average of the right and left ratio was calculated as TG:CCA. The median TG:CCA of 21 healthy dogs was 1.53, and it did not correlate either body weight or age. The median TG:CCA of 12 hypothyroid dogs was 0.81, which was significantly lower than that of 18 NTI dogs (1.81, P<0.001). If the cut off value <1.12 was used, TG:CCA indicated hypothyroidism with a sensitivity of 100%, specificity of 83%, and accuracy of 90%. Our data indicated that TG:CCA was independent of both body weight, which may contribute to consistent measurement of thyroid size. The results of this study suggest that TG:CCA is a promising tool for diagnosing canine hypothyroidism.
  • Noriyuki Nagata, Hiroshi Ohta, Arisa Yamada, Yong Bin Teoh, Osamu Ichii, Keitaro Morishita, Noboru Sasaki, Mitsuyoshi Takiguchi
    American journal of veterinary research 81 7 572 - 580 2020年07月 [査読有り]
     
    OBJECTIVE: To investigate the activities of gelatinases (matrix metalloproteinase [MMP]-2 and MMP-9) and serine proteases in the colorectal mucosa of Miniature Dachshunds (MDs) with inflammatory colorectal polyps (ICRPs). ANIMALS: 15 MDs with ICRPs and 5 dogs with non-ICRP-related large bowel diarrhea (controls). PROCEDURES: Zymographic methods were used to evaluate the activities of MMP-2, MMP-9, latent forms of MMP-2 and MMP-9 (pro-MMP-2 and pro-MMP-9), and serine proteases in inflamed and noninflamed tissue samples from MDs with ICRPs and in noninflamed tissue samples from control dogs. The associations of serine protease activities with MMP-2 or MMP-9 activity were also analyzed. RESULTS: Activities of pro-MMP-2 and pro-MMP-9 were detected in most tissue samples, regardless of the tissue type, whereas activities of MMP-2 and MMP-9 were not detected in control tissue samples. In the inflamed tissue samples from MDs with ICRPs, the activities of MMP-2, pro-MMP-9, and MMP-9 were significantly higher than those in the noninflamed tissue samples from those dogs. Serine protease activities were significantly higher in the inflamed and noninflamed tissue samples from MDs with ICRP, compared with findings for control tissue samples. A weak correlation was detected between serine protease activities and MMP-9 activity. CONCLUSIONS AND CLINICAL RELEVANCE: Study results suggested that gelatinase and serine protease activities are upregulated in the colorectal mucosa of MDs with ICRPs, possibly contributing to the pathogenesis of this disease through the functions of these enzymes in degradation of extracellular matrix and promotion of inflammatory cell migration and inflammatory responses.
  • Hiroshi Ohta, Jumpei Yamazaki, Jaroslav Jelinek, Teita Ishizaki, Yumiko Kagawa, Nozomu Yokoyama, Noriyuki Nagata, Noboru Sasaki, Mitsuyoshi Takiguchi
    The Journal of veterinary medical science 82 5 632 - 638 2020年05月20日 [査読有り]
     
    DNA methylation is the covalent modification of methyl groups to DNA mostly at CpG dinucleotides and one of the most studied epigenetic mechanisms that leads to gene expression variability without affecting the DNA sequence. Genome-wide analysis of DNA methylation identified the signatures that could define subtypes of human lymphoma patients. The objective of this study was to conduct the genome-wide analysis of DNA methylation in dogs with gastrointestinal lymphoma (GIL). Genomic DNA was extracted from endoscopic biopsies from 10 dogs with GIL. We performed Digital Restriction Enzyme Assay of DNA Methylation (DREAM) for genome-wide DNA methylation analysis that could provide highly quantitative information on DNA methylation levels of CpG sites across the dog genome. We successfully obtained data of quantitative DNA methylation level for 148,601-162,364 CpG sites per GIL sample. Next, we analyzed 83,132 CpG sites to dissect the differences in DNA methylation between GIL and normal peripheral blood mononuclear cells (PBMCs). We found 383-3,054 CpG sites that were hypermethylated in GIL cases compared to PBMCs. Interestingly, 773 CpG sites including promoter regions of 61 genes were identified to be commonly hypermethylated in more than half of the cases, suggesting conserved DNA methylation patterns that are abnormal in GIL. This study revealed that there was a large number of hypermethylated sites that are common in most of canine GIL. These abnormal DNA methylation could be involved in tumorigenesis of the canine GIL.
  • Noriyuki Nagata, Hiroshi Ohta, Nozomu Yokoyama, Yong Bin Teoh, Khoirun Nisa, Noboru Sasaki, Tatsuyuki Osuga, Keitaro Morishita, Mitsuyoshi Takiguchi
    Journal of veterinary internal medicine 34 2 659 - 668 2020年03月 [査読有り]
     
    BACKGROUND: In dogs with protein-losing enteropathy (PLE), data on the clinical characteristics of food-responsive PLE (FR-PLE) remain scarce. OBJECTIVE: To determine the clinical characteristics of FR-PLE in dogs responsive to ultralow-fat diet (ULFD) management. ANIMALS: Thirty-three dogs diagnosed with PLE based on standard diagnostic criteria. METHODS: Retrospective review of medical records. Clinical findings were compared between dogs with FR-PLE (FR-PLE group) and those with immunosuppressant-responsive PLE (IR-PLE) or nonresponsive PLE (NR-PLE) (IR/NR-PLE group). The area under the curve (AUC) of a receiver operating characteristic curve was used to evaluate the ability of factors to differentiate the FR-PLE and IR/NR-PLE groups. Survival time was compared between the FR-PLE and IR/NR-PLE groups. RESULTS: Twenty-three dogs responded to ULFD management and were diagnosed with FR-PLE. The canine chronic enteropathy clinical activity index (CCECAI) was significantly lower in the FR-PLE group than in the IR/NR-PLE group (P < .001). The AUC of CCECAI for differentiating the FR-PLE group was 0.935 (95% confidence interval [CI], 0.845-1.000) with an optimal cutoff value of 8 (sensitivity, 0.826; specificity, 0.889). Survival times were significantly longer in the FR-PLE group (median, not reached) than in the IR/NR-PLE group (median, 432 days; P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs that respond to ULFD management and are diagnosed with FR-PLE are expected to have a favorable prognosis. Clinical scores, specifically the CCECAI, could be useful for differentiating FR-PLE from IR-PLE or NR-PLE.
  • Angkhana Dermlim, Tatsuyuki Osuga, Kensuke Nakamura, Tomoya Morita, Khoirun Nisa, Kazuyoshi Sasaoka, Rommaneeya Leela-Arporn, Noriyuki Nagata, Masahiro Tamura, Noboru Sasaki, Hiroshi Ohta, Mitsuyoshi Takiguchi
    The Journal of veterinary medical science 81 7 949 - 957 2019年07月11日 [査読有り]
     
    The purpose of this study was to evaluate the cardiac acute volume loading effect on left atrial (LA) strain and strain rate (SR) parameters derived from two-dimensional speckle tracking echocardiography (2D-STE) in healthy dogs. Six healthy beagles were anesthetized and subjected to increase cardiac preload by intravenous infusion with lactated Ringer solution at 150 ml/kg/hr for 90 min. A Swan-Ganz catheter was placed to directly measure the mean pulmonary capillary wedge pressure (PCWP). Echocardiography was performed before (baseline) and at 15, 30, 45, 60, 75, and 90 min after acute volume loading began. Apical 4-chamber images focused on the LA were digitally recorded for later strain and SR analysis via 2D-STE. Acute volume loading significantly increased from baseline during LA strain and SR as assessed by the speckle tracking-based technique during reservoir and conduit function at 15 to 90 min after volume load began, and strain indices representing booster pump function were enhanced at 45 to 90 min. In addition, acute volume loading resulted in a significantly greater PCWP after fluid infusion. On multiple regression analysis, quadratic regression analysis was a better fit for the relationship between PCWP and all LA functional indices. Our findings indicated that LA function analyzed by strain and SR was enhanced during cardiac acute volume loading in healthy dogs. The change in strain and SR during acute volume loading should be interpreted with caution during the diagnosis of heart diseases related to volume overload.
  • Rommaneeya Leela-Arporn, Hiroshi Ohta, Masahiro Tamura, Noriyuki Nagata, Kazuyoshi Sasaoka, Angkhana Dermlim, Khoirun Nisa, Tatsuyuki Osuga, Keitaro Morishita, Noboru Sasaki, Mitsuyoshi Takiguchi
    Journal of veterinary internal medicine 33 4 1653 - 1659 2019年07月 [査読有り]
     
    BACKGROUND: Metabolomic analysis using blood samples has been suggested to be useful for the early detection of cancer. Among metabolites, plasma-free amino acid (PFAA) profiles are potential diagnostic biomarkers for several diseases including cancer. However, the relationship between PFAA concentrations and liver tumors in dogs remains unknown. OBJECTIVE: To determine the characteristics of PFAA profiles of dogs with hepatocellular carcinoma (HCC) and correlated clinical features. ANIMALS: Thirty-four client-owned dogs diagnosed with HCC (n = 26) and benign liver diseases (n = 8) and 11 age-matched healthy dogs. METHODS: Prospective study using heparinized blood samples from fasted dogs. Plasma was deproteinized, and the concentrations of 21 amino acids were measured using an automated high-performance liquid chromatography amino acid analyzer. RESULTS: Plasma glutamic acid concentrations were significantly different among groups (P < .0024 after Bonferroni correction). Compared to healthy dogs, dogs with HCC and benign liver diseases had significantly higher concentrations of glutamic acid by post hoc analysis. However, no significant difference in the PFAA profiles of HCC and benign liver diseases were detected. In addition, preoperative and postoperative PFAA profiles of dogs with HCC were not significantly different. CONCLUSIONS AND CLINICAL IMPORTANCE: Increased glutamic acid concentrations might play a role in the development or be a consequence of liver tumor formation. However, PFAA profiles of HCC could not be differentiated from those of benign lesions. In addition, glutamic acid concentrations did not change after surgical resection. These results indicate that PFAA profiles may not be useful biomarkers for detecting HCC in dogs.
  • Rommaneeya Leela-Arporn, Hiroshi Ohta, Masahiro Tamura, Noriyuki Nagata, Kazuyoshi Sasaoka, Angkhana Dermlim, Khoirun Nisa, Keitaro Morishita, Noboru Sasaki, Kensuke Nakamura, Satoshi Takagi, Kenji Hosoya, Mitsuyoshi Takiguchi
    The Journal of veterinary medical science 81 5 723 - 729 2019年05月31日 [査読有り]
     
    A definitive diagnosis of focal liver lesions (FLLs) requires invasive procedures for histopathologic examination. Thus, a simpler noninvasive diagnostic method, such as conventional ultrasonography combined with clinical data, is needed for the prediction of liver malignancy. The objective of this study was to examine the diagnostic accuracy of clinical data and ultrasonographic (US) features to differentiate benign and malignant liver lesions. Medical records and US images from dogs with FLLs that underwent abdominal US and histopathologic examinations following surgery or liver biopsy were retrospectively reviewed. Clinical data, including signalment, clinical signs and laboratory findings, and the US features of liver lesions that could act as predictive factors were assessed using univariate and multivariate analyses to evaluate the associations between predictive factors and liver malignancy. Based on the histopathologic results, 55 dogs with malignant lesions and 28 dogs with benign lesions were included in the study. The results of univariate analysis showed that several US features and platelet count were significantly associated with liver malignancy. Multivariate analysis revealed that the platelet count (thrombocytosis; odds ratio [OR]: 4.13, 95% confidence intervals [CI]: 1.81-9.41), lesion size (4.1 cm or greater; OR: 23.83, 95% CI: 3.74-151.95) and echotexture of FLLs (heterogenous; OR: 8.44; 95% CI: 1.37-51.91) were independent predictors for differentiating benign and malignant liver lesions, suggesting that a combination of clinical data and US findings of FLLs could predict liver malignancy in dogs.
  • Masashi Yuki, Reina Aoyama, Takashi Hirano, Reina Tawada, Mizuho Ogawa, Eiji Naitoh, Daiki Kainuma, Noriyuki Nagata
    BMC veterinary research 15 1 170 - 170 2019年05月24日 [査読有り]
     
    BACKGROUND: Dogs with various medical diseases are usually treated at hospitals; however, the prognostic markers in dogs remain unknown. The aim of this study was to investigate the ability of serum cortisol concentration (SCC) to predict the prognosis of dogs with medical diseases. At 0 and 24 h after hospitalization, the neutrophil count, lymphocyte count, blood glucose concentration, and SCC were measured. Survival for 30 days from the time of hospitalization was investigated, and the dogs were divided into a survivor group and a non-survivor group. RESULTS: The neutrophil count at 24 h, SCC at 24 h, increase in SCC from 0 to 24 h (Inc-SCC), and the rate of increase in SCC from 0 to 24 h (R-Inc-SCC) were significantly higher in the non-survivor group than in the survivor group. The area under the receiver operating characteristic (ROC) curve values for the neutrophil count at 24 h, SCC at 24 h, Inc-SCC, and R-Inc-SCC were 0.695, 0.72, 0.63, and 0.66, respectively. Using the highest area under the ROC curve value, the sensitivity and specificity of SCC at a cutoff level of 6.6 μg/dL for predicting mortality were 89.5 and 61.9%, respectively. Moreover, the Kaplan-Meier curves confirmed the significant prognostic influence of SCC at 24 h. CONCLUSIONS: SCC as a marker of stress is a useful biomarker for predicting the prognosis of dogs with medical diseases requiring hospital treatment.
  • 蚕白喪失性腸症の犬40例からの腸リンパ管拡張症の診断と治療に関する考察
    永田 矩之, 大田 寛, 横山 望, 佐々木 東, 大菅 辰幸, 森下 啓太郎, 滝口 満喜
    日本獣医師会雑誌 72 4 234 - 235 (公社)日本獣医師会 2019年04月
  • Khoirun Nisa, Sue Yee Lim, Masayoshi Shinohara, Tatsuyuki Osuga, Nozomu Yokoyama, Masahiro Tamura, Noriyuki Nagata, Kazuyoshi Sasaoka, Angkhana Dermlim, Rommaneeya Leela-Arporn, Tomoya Morita, Noboru Sasaki, Keitaro Morishita, Kensuke Nakamura, Hiroshi Ohta, Mitsuyoshi Takiguchi
    Journal of veterinary internal medicine 33 2 559 - 568 2019年03月 [査読有り]
     
    BACKGROUND: Contrast-enhanced ultrasonography (CEUS) can be used to evaluate intestinal perfusion in healthy dogs. It is helpful for diagnosing and monitoring inflammatory bowel disease in humans and could be useful for dogs with chronic intestinal diseases. OBJECTIVES: To examine duodenal perfusion in dogs with chronic inflammatory enteropathy (CIE) and intestinal lymphoma. ANIMALS: Client-owned dogs with CIE (n = 26) or intestinal lymphoma (n = 7) and dogs with gastrointestinal signs but histopathologically normal duodenum (controls, n = 14). METHODS: In this cross-sectional study, dogs with CIE were classified into remission (n = 16) and symptomatic (n = 10) groups based on clinical scores determined at the time of CEUS. The duodenum was scanned after IV injection of Sonazoid® (0.01 mL/kg). CEUS-derived perfusion parameters, including time-to-peak, peak intensity (PI), area under the curve (AUC), and wash-in and wash-out rates were evaluated. RESULTS: The PI was significantly higher in the symptomatic CIE group (median (range); 105.4 (89.3-128.8) MPV) than in the control group (89.9 (68.5-112.2) MPV). The AUC was significantly higher in the symptomatic CIE group (4847.9 (3824.3-8462.8) MPV.sec) than in the control (3448.9 (1559.5-4736.9) MPV.sec) and remission CIE (3862.3 (2094.5-6899.0) MPV.sec) groups. The PI and clinical score were positively correlated in the CIE group. No significant differences in perfusion parameters were detected between the lymphoma and CIE groups or the lymphoma and control groups. CONCLUSIONS AND CLINICAL IMPORTANCE: The PI and AUC can detect duodenal inflammation and hence are potentially useful for excluding a diagnosis of CIE.
  • 健康な犬における二次元スペックルトラッキング心エコーによる左心室長軸方向ストレイン解析に与える心臓容積負荷の影響(Effect of cardiac volume loading on left atrial longitudinal strain analysis derived from two-dimensional Speckle Tracking Echocardiography in healthy dogs)
    Dermlim Angkhana, 中村 健介, 森田 智也, 大菅 辰幸, Nisa Khoirun, Leela-arporn Rommaneeya, 笹岡 一慶, 永田 矩之, 田村 昌大, 佐々木 東, 大田 寛, 森下 啓太郎, 滝口 満喜
    日本獣医学会学術集会講演要旨集 161回 435 - 435 2018年08月
  • Khoirun Nisa, Sue Yee Lim, Tatsuyuki Osuga, Nozomu Yokoyama, Masahiro Tamura, Noriyuki Nagata, Kazuyoshi Sasaoka, Angkhana Dermlim, Rommaneeya Leela-Arporn, Tomoya Morita, Noboru Sasaki, Keitaro Morishita, Kensuke Nakamura, Hiroshi Ohta, Mitsuyoshi Takiguchi
    The Journal of veterinary medical science 80 3 453 - 459 2018年03月24日 [査読有り]
     
    Quantitative contrast-enhanced ultrasonography (CEUS) enables non-invasive and objective evaluation of intestinal perfusion by quantifying the intensity of enhancement on the intestine after microbubble contrast administration. During CEUS scanning, sedation is sometimes necessary to maintain animal cooperation. Nevertheless, the effect of sedative administration on the canine intestinal CEUS is unknown. This study aimed to investigate the effect of sedation with a combination of butorphanol and midazolam on the duodenal CEUS-derived perfusion parameters of healthy dogs. For this purpose, duodenum was imaged following contrast administration (Sonazoid®, 0.01 ml/kg) in six healthy beagles before and after intravenous injection of a combination of butorphanol (0.2 mg/kg) and midazolam (0.1 mg/kg). Furthermore, hemodynamic parameters including blood pressure and heart rate were recorded during the procedure. Five CEUS derived perfusion parameters including time-to-peak (TTP), peak intensity (PI), area under the curve (AUC), wash-in and wash-out rates (WiR and WoR, respectively) before and after sedation were statistically compared. The result showed that no significant change was detected in any of perfusion parameters. Systolic and mean arterial pressures significantly reduced after sedative administration, but diastolic arterial pressure and heart rate did not significantly change. Moreover, no significant partial correlation was observed between perfusion parameters and hemodynamic parameters. Thus, we concluded that the combination did not cause significant influence in duodenal CEUS perfusion parameters and could be a good option for sedation prior to duodenal CEUS in debilitated dogs.
  • Khoirun Nisa, Sue Yee Lim, Masayoshi Shinohara, Noriyuki Nagata, Kazuyoshi Sasaoka, Angkhana Dermlim, Rommaneeya Leela-Arporn, Tomoya Morita, Nozomu Yokoyama, Tatsuyuki Osuga, Noboru Sasaki, Keitaro Morishita, Kensuke Nakamura, Hiroshi Ohta, Mitsuyoshi Takiguchi
    The Journal of veterinary medical science 79 9 1585 - 1590 2017年09月29日 [査読有り]
     
    Contrast-enhanced ultrasonography (CEUS) with microbubbles as a contrast agent allows the visualization and quantification of tissue perfusion. The assessment of canine intestinal perfusion by quantitative CEUS may provide valuable information for diagnosing and monitoring chronic intestinal disorders. This study aimed to assess the repeatability (intraday variability) and reproducibility (interday variability) of quantitative duodenal CEUS in healthy dogs. Six healthy beagles underwent CEUS three times within one day (4-hr intervals) and on two different days (1-week interval). All dogs were sedated with a combination of butorphanol (0.2 mg/kg) and midazolam (0.1 mg/kg) prior to CEUS. The contrast agent (Sonazoid®) was administered using the intravenous bolus method (0.01 ml/kg) for imaging of the duodenum. Time-intensity curves (TIC) were created by drawing multiple regions of interest (ROIs) in the duodenal mucosa, and perfusion parameters, including the time-to-peak (TTP), peak intensity (PI), area under the curve (AUC), and wash-in and wash-out rates (WiR and WoR, respectively), were generated. Intraday and interday coefficients of variation (CVs) for TTP, PI, AUC, WiR and WoR were <25% (range, 2.27-23.41%), which indicated that CEUS was feasible for assessing duodenal perfusion in healthy sedated dogs. A further study of CEUS in dogs with chronic intestinal disorders is necessary to evaluate its clinical applicability.
  • 慢性腸疾患の犬における十二指腸の定量的造影超音波法(Quantitative contrast-enhanced ultrasonography of duodenum in dogs with chronic enteropathy)
    Khoirun Nisa, 大田 寛, 横山 望, 田村 昌大, 永田 矩之, 笹岡 一慶, Dermlim Angkhana, Leela-Arporn Rommaneeya, 森田 智也, 大菅 辰幸, 佐々木 東, 森下 啓太郎, 滝口 満喜
    日本獣医学会学術集会講演要旨集 160回 477 - 477 2017年08月
  • Nozomu Yokoyama, Hiroshi Ohta, Yumiko Kagawa, Noriyuki Nagata, Khoirun Nisa, Tomoya Morita, Tatsuyuki Osuga, Noboru Sasaki, Keitaro Morishita, Kensuke Nakamura, Mitsuyoshi Takiguchi
    Veterinary immunology and immunopathology 188 78 - 83 2017年06月 [査読有り]
     
    Inflammatory colorectal polyps (ICRPs) in miniature dachshunds (MDs) are a possible novel form of breed-specific canine inflammatory bowel disease (IBD). In this pilot study, we investigated the effects of different Toll like receptor (TLR2, TLR4, TLR5 and TLR9) ligands on pro-inflammatory cytokines (IL-1β, IL-6, IL-8 and TNF-α) gene expression in ex vivo-cultured colorectal samples from four MDs with ICRPs and four healthy MDs. At baseline, no significant difference in the mRNA expression levels of TLRs and pro-inflammatory cytokines was observed between cases and control MDs. After 4-h incubation, the relative ratios of TNF-α mRNA expression in the TLR2- or TLR4-stimulated colorectal samples, and IL-1β mRNA expression in the TLR9-stimulated colorectal samples form cases showed higher tendency compared with healthy MDs (P<0.05), although statistically not significant. The results of this pilot study using small number of cases indicated that reactivity against TLR2, TLR4 or TLR9 ligand in the production of pro-inflammatory cytokines might be enhanced in the colorectal mucosa of ICRPs. Further research is needed to perform the functional analysis of TLRs in the sole cell population using intestinal epithelial primary culture and the mononuclear cells isolated from colonic mucosa.
  • N Nagata, K Kojima, M Yuki
    Journal of veterinary internal medicine 31 1 22 - 28 2017年01月 [査読有り]
     
    BACKGROUND: Although pituitary-dependent hyperadrenocorticism (PDH) is one of the most common endocrinopathies in dogs, the effects of withholding treatment on survival time in dogs with PDH remain unclear. HYPOTHESIS/OBJECTIVES: The purpose of this study was to clarify the effects of treatment in dogs with PDH by comparing survival times between dogs treated with trilostane and untreated dogs. ANIMALS: Forty-three dogs diagnosed with PDH at a primary-care hospital in Japan between June 2009 and January 2014. METHODS: Retrospective cohort study. The medical records of dogs with PDH treated with trilostane (n = 17) or left untreated (n = 26) were reviewed retrospectively. Survival analysis at 2 years after diagnosis of PDH was performed. RESULTS: Median survival time for the trilostane group was not reached (95% confidence interval [CI], 443 days-not applicable) and was significantly longer than the 506 days (95% CI, 292-564 days; P = .016) for the untreated group. Multivariate Cox proportional hazards analysis (including age at diagnosis, basal cortisol concentration at diagnosis, and treatment group) only identified assignment to the untreated group (hazard ratio, 5.01; 95% CI, 1.63-15.44) as associated with increased mortality. CONCLUSIONS AND CLINICAL IMPORTANCE: The results of this retrospective cohort study suggest that withholding treatment for dogs with PDH might be associated with a higher risk of death. This represents the largest study to date to report survival times of untreated dogs with PDH.
  • Noriyuki Nagata, Masashi Yuki, Ryota Asahina, Hiroki Sakai, Sadatoshi Maeda
    The Journal of veterinary medical science 78 8 1333 - 7 2016年09月01日 [査読有り]
     
    A 12-year-old male entire Miniature Pinscher presented with excoriations at various body sites, progressively forming ulcers and enlarging until arrested by treatment. Based on the clinical presentation and histopathological analyses, sterile neutrophilic dermatosis was suspected. Therefore, the dog was started on prednisolone. Marked improvement was achieved with prednisolone treatment, suggesting a diagnosis of pyoderma gangrenosum (PG). Transcription levels of cytokine mRNA in lesional skin before and after treatment from this dog were quantified by real-time RT-PCR. Transcription levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-8 and IL-17A were higher in lesional skin before treatment than after treatment. Levels of various cytokines could be increased in lesional skin of dogs with PG as well as in human patients with PG.
  • Koji Kawano, Hidekatsu Shimakura, Noriyuki Nagata, Yuki Masashi, Akemi Suto, Yukinori Suto, Shohei Uto, Hiromichi Ueno, Takehiro Hasegawa, Takahiro Ushigusa, Takashi Nagai, Yasunori Arawatari, Kazuki Miyaji, Keitaro Ohmori, Takuya Mizuno
    The Journal of veterinary medical science 78 8 1377 - 80 2016年09月01日 [査読有り]
     
    There have been limited reports on the prevalence of adverse food reactions among dogs suffering from chronic enteropathy (CE) in Japan. We examined the prevalence and histological features of food-responsive enteropathy (FRE) in a total of 32 dogs with history of CE. Fourteen of 18 cases (56.2%) diagnosed as FRE had lymphocytic-plasmacytic enteritis or eosinophilic enteritis by histopathological examination. Characteristic histopathological changes indicating FRE were not identified in 18 cases, though 4 cases did not show any abnormalities. Results collected from this study provided important information that can help to change the way dogs with CE are treated in the future.
  • Noriyuki Nagata, Masashi Yuki
    The Canadian veterinary journal = La revue veterinaire canadienne 56 9 931 - 3 2015年09月 [査読有り]
     
    Two dogs were diagnosed with myotonia associated with hyperadrenocorticism and treated with trilostane. One dog showed temporary improvement, but the other dog showed no improvement. The dogs survived 2383 and 1902 days, respectively. Findings suggest that myotonia persists despite treatment, but this condition is not associated with a poor prognosis for survival.
  • 永田矩之, 湯木正史
    動物臨床医学 22 3 2013年
  • Noriyuki Nagata, Masashi Yuki, Takashi Hasegawa
    The Journal of veterinary medical science 73 12 1585 - 9 2011年12月 [査読有り]
     
    Intraocular pressure (IOP) evaluated by applanation tonometry via TONO-PEN XL (TP), and rebound tonometry via TonoVet (TV) were compared in enucleated canine eyes with varied pressure of the anterior chamber (AC) and in clinical cases. TV measured IOP values were lower than IOP measurements of TP in the enucleated eyes with 5-10 mmHg of AC (P<0.0001), though there was no significant difference in IOP values obtained with TP and TV on the pressure ranges of 15-20 mmHg. However, TP detected IOP values were lower than IOP measurements of TV in the eyes with over 25 mmHg of AC (P<0.0001). The results of clinical cases were similar to the enucleated eye model. There was no significant difference in IOP values obtained from TP and TV in dogs with normotensive eyes. IOP measurements of TP were lower than those of TV in glaucomatous eyes (P<0.0001). TV was a reliable tonometer for measurement of IOP in hypertensive eyes, whereas it was less accurate than TP in hypotensive eyes. The characteristics of TP and TV should be considered in the evaluation of IOP in practice.

その他活動・業績

受賞

  • 2021年06月 2020年JVMS優秀論文賞
     
    受賞者: 佐々木東;永田矩之;森下啓太郎;大菅辰幸;笹岡一慶;横山望;大田寛;滝口満喜
  • 2018年09月 平成30年度日本小動物獣医学会北海道地区学会賞
     
    受賞者: 永田矩之
  • 2015年02月 第11回日本獣医内科学アカデミー学術大会臨床研究アワード
     
    受賞者: 永田矩之

共同研究・競争的資金等の研究課題

  • 犬種特異的な炎症性腸疾患における炎症と癌化に関与する遺伝子の探索と機能解析
    日本学術振興会:科学研究費助成事業 特別研究員奨励費
    研究期間 : 2018年04月 -2021年03月 
    代表者 : 永田 矩之
     
    本年度は、症例対照研究を行い、PLG遺伝子を犬の炎症性結直腸ポリープ疾患感受性遺伝子の一つとして選定した。罹患したミニチュア・ダックスフント(症例群)と罹患していないミニチュア・ダックスフント(対照群)の血液からDNAを抽出し、これまでの研究で選定した候補遺伝子の変異領域をPCR法で増幅した後にシーケンス解析を行った。その結果、PLG 遺伝子に認められたミスセンス変異(c.478A>T p.Asn160Tyr)のアレル頻度が疾患群で有意に高く、炎症性結直腸ポリープ発症との関連が示唆された。PLG遺伝子は、セリンプロテアーゼの一つであるプラスミンの酵素前駆体、プラスミノーゲンをコードする遺伝子である。プラスミノーゲンおよびプラスミンは線溶系において主たる役割を果たしている一方で、炎症細胞の遊走、腫瘍細胞の浸潤ならびに炎症性サイトカインの産生に関与していることが明らかになっている。そこで、炎症性結直腸ポリープの病変局所におけるプラスミン活性をザイモグラフィーにより検討した結果、病変部のプラスミン活性はコントロールに比べて有意に上昇していた。以上の結果から、PLG遺伝子に認められた変異は、プラスミン活性を増大させることで炎症性結直腸ポリープ発症と関連する可能性が考えられた。 次に、PLG c.478A>T p.Asn160Tyrの病態における役割を明らかにするため、犬プラスミノーゲンの組換えタンパク質を作製した。犬PLG遺伝子をクローニングし、哺乳類細胞を用いてタンパク質を発現させた。発現させたタンパクを含む上清を用いてザイモグラフィーを行ったところ、プラスミン活性が確認され、今後の機能試験に使用できることを確認した。変異型に関しては、PCR法を用いたSite-directed mutagenesisによりc.478A>Tの変異を含むプラスミドを作製した。

教育活動情報

主要な担当授業

  • 内科学実習
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 獣医学部


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