研究者データベース

森下 啓太郎(モリシタ ケイタロウ)
獣医学研究院 附属動物病院
助教

基本情報

所属

  • 獣医学研究院 附属動物病院

職名

  • 助教

学位

  • 博士(獣医学)(北海道大学)

ホームページURL

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
  • ライフサイエンス / 獣医学
  • ライフサイエンス / 獣医学

所属学協会

  • 動物臨床医学会   日本獣医画像診断学会   日本獣医師会   日本獣医学会   

研究活動情報

論文

  • Noriyuki Nagata, Hiryu Sawamura, Keitaro Morishita, Kenji Hosoya, Nozomu Yokoyama, Kazuyoshi Sasaoka, Noboru Sasaki, Kensuke Nakamura, Yoshinori Ikenaka, Mitsuyoshi Takiguchi
    The Journal of veterinary medical science 2022年05月27日 
    The urinary corticoid to creatinine ratio (UCCR) is one of the most commonly used screening tests for canine hypercortisolism (HC). In this study, a reference interval was established for UCCR using IMMULITE 2000 XPi, the latest chemiluminescence enzyme immunoassay. The diagnostic performance of this method for UCCR in canine HC was also evaluated. The median UCCR was 1.06 × 10-5 (range: 0.28-2.49) for 58 healthy dogs, and an upper reference limit of 1.98 × 10-5 (90% confidence interval: 1.76-2.15) was determined. The median UCCR in the 12 dogs with HC (7.38 × 10-5, range 1.86-29.98) was significantly higher than that in the 16 dogs with mimic-HC (1.59 × 10-5, range 0.47-3.42, P<0.001). The area under the curve for UCCR to differentiate HC dogs from mimic-HC dogs was 0.971, with a sensitivity of 91.7% and specificity of 100% when the cut-off value was set at 3.77 × 10-5. The UCCR of 16 paired urine samples collected at home and in hospital showed that the UCCR of samples collected in the hospital was significantly higher than that of samples collected at home (mean difference 3.30 × 10-5, 95% confidence interval: 0.70-5.90, P=0.001). In summary, we established the upper reference limit for UCCR using IMMULITE 2000 XPi in dogs and confirmed that UCCR is a useful diagnostic test for HC in dogs if urine samples are collected at home.
  • Tatsuyuki Osuga, Tomoya Morita, Noboru Sasaki, Keitaro Morishita, Hiroshi Ohta, Mitsuyoshi Takiguchi
    Journal of veterinary internal medicine 35 6 2607 - 2615 2021年11月06日 [査読有り]
     
    BACKGROUND: The interaction between the left ventricle (LV) and systemic arterial systems, known as left ventricular-arterial coupling (VAC), has been evaluated based on the effective arterial elastance (Ea) to LV end-systolic elastance (Ees) ratio (Ea/Ees). The Ea reflects the total arterial load of LV, whereas Ees reflects the LV systolic function. A recent study found that inappropriate VAC based on increased Ea/Ees estimated by echocardiography is associated with advanced disease severity in dogs with myxomatous mitral valve disease (MMVD). HYPOTHESIS: Inappropriate VAC assessed by echocardiographic estimation of Ea/Ees is associated with a worse prognosis in dogs with MMVD. ANIMALS: Eighty-nine dogs with MMVD. METHODS: Prospective cohort study. Dogs underwent echocardiographic examinations at enrollment. The Ea was estimated using the formula: mean blood pressure/(forward stroke volume/body weight). The Ees was estimated using the formula: mean blood pressure/(LV end-systolic volume/body weight). The Ea/Ees was calculated. RESULTS: By end of study, 22 dogs died of cardiac-related causes with 67 dogs censored. Dogs with increased Ea/Ees (Ea/Ees >0.34; median survival time, 527 days; 95% confidence interval [CI], 322 days-not determinable) had a shorter survival time (P < .0001) than those without increased Ea/Ees (Ea/Ees ≤0.34; median survival time, >1112 days; 95% CI, not determinable). Multivariate Cox proportional hazard analysis showed that Ea/Ees, body weight, peak systolic mitral annular velocity, and the peak early diastolic transmitral velocity-to-peak early diastolic mitral annular velocity ratio were independent predictors of cardiac-related death among echocardiographic indices. CONCLUSIONS AND CLINICAL IMPORTANCE: Inappropriate VAC assessed based on echocardiographically-estimated Ea/Ees is associated with a worse prognosis in dogs with MMVD.
  • 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 83 11 1634 - 1642 2021年09月17日 
    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.
  • Masahiro Tamura, Hiroshi Ohta, Tatsuyuki Osuga, Noboru Sasaki, Keitaro Morishita, Mitsuyoshi Takiguchi
    Veterinary radiology & ultrasound : the official journal of the American College of Veterinary Radiology and the International Veterinary Radiology Association 62 4 483 - 489 2021年07月 
    Two-dimensional shear wave elastography (2D-SWE) can be used to quantitatively evaluate the elastic modulus of the liver as shear wave velocity (SWV), which can noninvasively predict clinically relevant hepatic fibrosis in both dogs and humans. However, extrahepatic biliary obstruction (EHBO), regardless of the presence of clinically relevant hepatic fibrosis, can influence SWVs in humans and thus may interfere with hepatic fibrosis prediction using 2D-SWE in dogs. The aim of this prospective, observational, and one-group pretest-posttest study is to investigate whether SWV measured by 2D-SWE displays a difference between dogs with and without EHBO. A total of 20 dogs were included (7 with EHBO and 13 with gallbladder pathology but no EHBO) that underwent preoperative SWV measurement using 2D-SWE. In all dogs, stages of hepatic fibrosis were evaluated histopathologically using a scoring scheme. In addition, postoperative SWVs in dogs with EHBO relieved via laparotomy were also evaluated. The median (range) SWVs in the dogs with and without EHBO were 1.91 (1.81-2.54) m/s and 1.57 (1.37-1.64) m/s, respectively. Although there was no significant difference in the histopathological hepatic fibrosis stages between the dogs with and without EHBO, the preoperative SWVs in the dogs with EHBO were significantly higher than in dogs without EHBO (P = .0004), and SWVs were found to decrease significantly after surgery (P = .0097). This study demonstrates that EHBO can increase the SWV of dogs without clinically relevant hepatic fibrosis and can interfere with the prediction of noninvasive hepatic fibrosis using 2D-SWE.
  • 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 
    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.
  • Satoshi Takagi, Eiichi Kanai, Keitaro Morishita, Hiroko Ogawa, Junya Ogawa
    The Journal of veterinary medical science 83 1 69 - 72 2021年01月14日 
    Segmental caudal vena cava (CVC) aplasia is a rare congenital vascular anomaly in dogs. Two dogs were diagnosed by CT imaging to have right adrenal tumors with concomitant segmental CVC aplasia. During surgery, a firm connection between the right adrenal gland and CVC was observed in both cases. The adrenal glands were found ventral to the CVC and the adrenal tumor was resected including the vascular wall. CVC venectomy for tumor removal will be required if the right adrenal gland is displaced in dogs with segmental CVC aplasia, even if there is no intravascular invasion.
  • Tatsuyuki Osuga, Tomoya Morita, Noboru Sasaki, Keitaro Morishita, Hiroshi Ohta, Mitsuyoshi Takiguchi
    Journal of veterinary internal medicine 35 1 78 - 87 2021年01月 
    BACKGROUND: The effective arterial elastance (Ea) to left ventricular (LV) end-systolic elastance (Ees) ratio (Ea/Ees) is an index of the interaction between LV and systemic arterial systems, left ventricular-arterial coupling (VAC). The Ea is an index of total arterial load of the LV, whereas Ees is an index of LV systolic function. In humans, inappropriate VAC based on increased Ea/Ees estimated using echocardiography is associated with more advanced heart disease severity. HYPOTHESIS: Left ventricular-arterial coupling assessed by echocardiographic estimation of Ea/Ees is associated with disease severity in dogs with myxomatous mitral valve disease (MMVD). ANIMALS: Ninety MMVD dogs and 61 healthy dogs. METHODS: Prospective cross-sectional study. The MMVD dogs were classified into stages B1, B2, or C according to American College of Veterinary Internal Medicine guidelines. Effective arterial elastance was echocardiographically estimated using the formula: mean blood pressure/(forward stroke volume/body weight). End-systolic elastance was echocardiographically estimated using the formula: mean blood pressure/(LV end-systolic volume/body weight). The ratio Ea/Ees was calculated. RESULTS: The ratio Ea/Ees was higher in stage B2 dogs than in healthy dogs and dogs stage B1 (both P < .0001), and higher in stage C dogs than in healthy dogs and dogs in the other 2 stages (healthy vs C and B1 vs C, P < .0001; B2 vs C, P = .0005). Multivariable logistic regression analysis showed that Ea/Ees and the peak velocity of early diastolic transmitral flow to isovolumic relaxation time ratio were independent predictors of stage C among echocardiographic indices in MMVD dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Inappropriate VAC assessed by echocardiographically estimated Ea/Ees is associated with advanced disease severity in dogs with MMVD.
  • 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 
    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 
    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][通常論文]
     
    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.
  • 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][通常論文]
     
    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.
  • Rommaneeya Leela-Arporn, Hiroshi Ohta, Genya Shimbo, Kiwamu Hanazono, Tatsuyuki Osuga, Keitaro Morishita, Noboru Sasaki, Mitsuyoshi Takiguchi
    The Journal of veterinary medical science 81 12 1697 - 1704 2019年12月18日 [査読有り][通常論文]
     
    Thus far, there are few computed tomography (CT) characteristics that can distinguish benign and malignant etiologies. The criteria are complex, subjective, and difficult to use in clinical applications due to the high level of experience needed. This study aimed to identify practical CT variables and their clinical relevance for broadly classifying histopathological diagnoses as benign or malignant. In this prospective study, all dogs with liver nodules or masses that underwent CT examination and subsequent histopathological diagnosis were included. Signalments, CT findings and histopathological diagnoses were recorded. Seventy liver nodules or masses in 57 dogs were diagnosed, comprising 18 benign and 52 malignant lesions. Twenty-three qualitative and quantitative CT variables were evaluated using univariate and stepwise multivariate analyses, respectively. Two variables, namely, the postcontrast enhancement pattern of the lesion in the delayed phase (heterogeneous; odds ratio (OR): 14.7, 95% confidence interval (CI): 0.82-262.03, P=0.0429) and the maximal transverse diameter of the lesion (>4.5 cm; OR: 33.3, 95% CI: 2.29-484.18, P=0.0006), were significantly related to the differentiation of benign from malignant liver lesions, with an area under the curve of 0.8910, representing an accuracy of 88.6%. These findings indicate that features from triple-phase CT can provide information for distinguishing pathological varieties of focal liver lesions and for clinical decision making. Evaluations of the maximal transverse diameter and postcontrast enhancement pattern of the lesion included simple CT features for predicting liver malignancy with high accuracy in clinical settings.
  • Tomoya Morita, Kensuke Nakamura, Tatsuyuki Osuga, Kiwamu Hanazono, Keitaro Morishita, Mitsuyoshi Takiguchi
    The Journal of veterinary medical science 81 9 1259 - 1265 2019年09月03日 [査読有り][通常論文]
     
    A 12-year-old neutered female American cocker spaniel weighing 9.9 kg was presented for evaluation with a 2-day history of dyspnea and anorexia. Echocardiography revealed severe pulmonary hypertension (estimated systolic pulmonary arterial pressure, 93.4 mmHg) with right heart enlargement, pulmonary arterial dilation, and right ventricular dysfunction. The dilation of left heart and congenital cardiac shunt were not observed. Pulmonary thromboembolism (PTE) was confirmed by computed tomographic angiography. After treatment with antiplatelet and anticoagulant, the clinical sign and the echocardiographic abnormality of right heart were improved. These echocardiographic findings are not specific for PTE, but it can be useful as a rule-in test for PTE when other causes of pulmonary hypertension are excluded and a monitor of therapeutic efficacy.
  • Masahiro Tamura, Hiroshi Ohta, Genya Shimbo, Tatsuyuki Osuga, Noboru Sasaki, Keitaro Morishita, Yumiko Kagawa, Mitsuyoshi Takiguchi
    Journal of veterinary internal medicine 33 5 2067 - 2074 2019年09月 [査読有り][通常論文]
     
    BACKGROUND: Two-dimensional shear wave elastography (2D-SWE) can noninvasively evaluate hepatic elastic modulus as shear wave velocity (SWV). Additionally, it may predict the presence of clinical relevant hepatic fibrosis (≥F2) in dogs with hepatic disease. OBJECTIVES: To investigate whether SWV measured by 2D-SWE can differentiate between dogs with (≥F2) and without (F0-1) clinically relevant hepatic fibrosis. ANIMALS: Twenty-eight client-owned dogs with hepatic disease and 8 normal healthy Beagle dogs were enrolled. METHODS: In this cross-sectional prospective study, SWVs were measured using 2D-SWE in all dogs. Hepatic fibrosis stages and necroinflammatory activity grades were histopathologically evaluated using a histological scoring scheme that was adapted from the Ishak schema used in human medicine. RESULTS: Median SWVs were significantly higher in dogs with clinically relevant hepatic fibrosis (2.04 m/s; range, 1.81-2.26 m/s) than in healthy dogs (1.51 m/s; range, 1.44-1.66 m/s; P = .007), and dogs without clinically relevant hepatic fibrosis (1.56 m/s; range, 1.37-1.67 m/s; P < .001). However, no significant difference was found in the SWVs between dogs without clinically relevant hepatic fibrosis and healthy dogs (P = .99). Furthermore, median SWVs were not significantly different among dogs with necroinflammatory activity, those without necroinflammatory activity, and healthy dogs (Kruskal-Wallis test, P = .12). CONCLUSIONS AND CLINICAL IMPORTANCE: The 2D-SWE may be useful for predicting the presence of hepatic fibrosis in dogs with hepatic disease.
  • Masahiro Tamura, Kensuke Nakamura, Tatsuyuki Osuga, Genya Shimbo, Noboru Sasaki, Keitaro Morishita, Hiroshi Ohta, Mitsuyoshi Takiguchi
    The Journal of veterinary medical science 81 8 1104 - 1108 2019年08月09日 [査読有り][通常論文]
     
    Contrast-enhanced ultrasonography (CEUS) is useful to distinguish benign and malignant focal liver lesions in dogs. Cholangiocellular adenoma is an extremely rare benign tumor in dogs and has not been examined using CEUS with Sonazoid. The aim of this study was to describe findings of CEUS with Sonazoid in three dogs with cholangiocellular adenoma. All three dogs showed contrast defects in the Kupffer phase and these findings mimicked malignant neoplasia during the Kupffer phase. Moreover, all dogs showed early washout and hypoechoic lesions relative to the surrounding normal liver parenchyma in the portal phase. To our knowledge, this is the first study to report that CEUS findings of cholangiocellular adenoma with Sonazoid mimicked malignancy in three dogs.
  • Khoirun Nisa, Hiroshi Ohta, Nozomu Yokoyama, Masahiro Tamura, Noriyuki Nagata, Kazuyoshi Sasaoka, Angkhana Dermlim, Rommaneeya Leela-Arporn, Tomoya Morita, Tatsuyuki Osuga, Noboru Sasaki, Keitaro Morishita, Kensuke Nakamura, Yumiko Kagawa, Mitsuyoshi Takiguchi
    JAPANESE JOURNAL OF VETERINARY RESEARCH 67 3 221 - 227 2019年08月 [査読有り][通常論文]
     
    Ultra low fat diet (ULFD) has shown a good therapeutic effect in dogs with intestinal lymphangiectasia secondary to CE (IL-CE). As we hypothesized that the mechanism of ULFD may involve the resolution of immunological impairment in IL-CE dogs, our study aimed to investigate the effect of ULFD on the circulating regulatory T cell (Treg) of IL-CE dogs. Treg frequency of pre- and post-ULFD blood samples from dogs with IL-CE (n = 3) were measured using flow cytometry. Treg frequency in IL-CE group before ULFD treatment showed lower tendency when compared to healthy control (mean +/- SD; 2.0 +/- 1.6% and 4.3 +/- 1.4%, respectively), and showed increased tendency after ULFD (mean +/- SD; 4.5 +/- 3.5%). The results suggested that ULFD might restore circulating Treg frequency of IL-CE dogs.
  • 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][通常論文]
     
    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.
  • Yu Tamura, Hiroshi Ohta, Yumiko Kagawa, Tatsuyuki Osuga, Keitaro Morishita, Noboru Sasaki, Mitsuyoshi Takiguchi
    Journal of veterinary internal medicine 33 4 1602 - 1607 2019年07月 [査読有り][通常論文]
     
    BACKGROUND: Lymphocytic-plasmacytic enteritis is the common form of idiopathic inflammatory bowel disease (IBD) in dogs. In human IBD, disturbances of amino acid metabolism have been demonstrated to be involved in the pathophysiology of IBD. Therefore, plasma amino acid profile might represent a novel marker of human IBD. OBJECTIVES: To determine the plasma amino acid profiles of dogs with IBD and its usefulness as a novel marker of IBD in dogs. ANIMALS: Fasting blood plasma was obtained from 10 dogs with IBD and 12 healthy dogs. METHODS: All IBD dogs were prospectively included in this study, and heparinized blood samples were collected. The plasma concentrations of 21 amino acids were determined using the ninhydrin method. The relationships among the plasma amino acid concentrations and plasma C-reactive protein (CRP) concentration, canine chronic enteropathy clinical activity index (CCECAI), and overall World Small Animal Veterinary Association (WSAVA) score were investigated. RESULTS: Median concentration (nmol/mL) of methionine [46.2; range, 30.0-59.3], proline [119.4; range, 76.7-189.2], serine [115.1; range, 61.4-155.9], and tryptophan [17.4; range, 11.9-56.3]) were significantly lower than in control dogs [62.6; range, 51.0-83.6, 199.1; range, 132.5-376.7, 164.3; range, 124.7-222.9, and 68.3; range, 35.7-94.8, respectively]. A negative correlation was identified between the plasma serine concentration and CCECAI (r s = -.67, P = .03), but there were no correlations between plasma amino acid concentrations and CRP concentration or overall WSAVA score. CONCLUSIONS AND CLINICAL IMPORTANCE: Plasma serine concentration might represent a novel maker of IBD in dogs.
  • Leela-Arporn R, Ohta H, Nagata N, Sasaoka K, Tamura M, Dermlim A, Nisa K, Morishita K, Sasaki N, Nakamura K, Takagi S, Hosoya K, Takiguchi M
    Veterinary journal (London, England : 1997) 248 74 - 78 2019年06月 [査読有り][通常論文]
  • Morita, T, Nakamura, K, Osuga, T, Morishita, K, Sasaki, N, Ohta, H. Takiguchi, M
    Journal of Veterinary Cardiology 23 1 1 - 14 2019年06月 [査読有り][通常論文]
  • 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][通常論文]
     
    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.
  • Masahiro Tamura, Hiroshi Ohta, Khoirun Nisa, Tatsuyuki Osuga, Noboru Sasaki, Keitaro Morishita, Mitsuyoshi Takiguchi
    American journal of veterinary research 80 4 378 - 384 2019年04月 [査読有り][通常論文]
     
    OBJECTIVE: To assess liver and spleen stiffness in healthy dogs by use of a novel 2-D shear wave elastography (SWE) technique and to investigate the repeatability and reproducibility of the technique. ANIMALS: 8 healthy adult Beagles. PROCEDURES: 2-D SWE was performed on each dog to assess liver and spleen stiffness. Repeatability (intraday variability) and reproducibility (interday variability) of 2-D SWE were investigated. For all 8 dogs, 2-D SWE was performed 3 times in 1 day (4-hour intervals) and on 3 separate days (1-week interval). Data were expressed as mean ± SD values for shear wave velocity and the Young modulus in the liver and spleen. Intraday and interday coefficients of variation were assessed for all variables. RESULTS: Mean ± SD shear wave velocity obtained for the liver and spleen was 1.51 ± 0.08 m/s and 2.18 ± 0.27 m/s, respectively. Mean value for the Young modulus obtained for the liver and spleen was 6.93 ± 0.79 kPa and 14.66 ± 3.79 kPa, respectively. Elasticity values were significantly higher for the spleen than for the liver. Intraday and interday coefficients of variation for all variables were < 25% (range, 3.90% to 20.70%). CONCLUSIONS AND CLINICAL RELEVANCE: 2-D SWE was a feasible technique for assessing liver and spleen stiffness of healthy dogs. Future studies on the application of 2-D SWE for dogs with chronic hepatitis, cirrhosis, and portal hypertension are needed to evaluate the clinical applicability of 2-D SWE.
  • Nisa K, Lim SY, Shinohara M, Osuga T, Yokoyama N, Tamura M, Nagata N, Sasaoka K, Dermlim A, Leela-Arporn R, Morita T, Sasaki N, Morishita K, Nakamura K, Ohta H, Takiguchi M
    Journal of Veterinary Internal Medicine 33 2 559 - 568 2019年03月 [査読有り][通常論文]
     
    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.
  • Masahiro Tamura, Hiroshi Ohta, Khoirun Nisa, Tatsuyuki Osuga, Noboru Sasaki, Keitaro Morishita, Mitsuyoshi Takiguchi
    Veterinary radiology & ultrasound : the official journal of the American College of Veterinary Radiology and the International Veterinary Radiology Association 60 2 192 - 200 2019年03月 [査読有り][通常論文]
     
    Extrahepatic-congenital portosystemic shunt is a vascular anomaly that connects the portal vein to the systemic circulation and leads to a change in hepatic microvascular perfusion. However, an assessment of hepatic microvascular perfusion is limited by conventional diagnostic modalities. The aim of this prospective, exploratory study was to assess hepatic microvascular perfusion in dogs with extrahepatic-congenital portosystemic shunt using contrast-enhanced ultrasonography (CEUS) using perfluorobutane (Sonazoid® ). A total of 17 dogs were included, eight healthy dogs and nine with extrahepatic-congenital portosystemic shunt. The time-to-peak (TTP), rising time (RT), and rising rate (RR) in the hepatic artery, portal vein, and hepatic parenchyma, as well as the portal vein-to-hepatic parenchyma transit time (ΔHP-PV) measured from time-intensity curve on CEUS were compared between healthy and extrahepatic-congenital portosystemic shunt dogs. The RT of the hepatic artery in extrahepatic-congenital portosystemic shunt dogs was significantly earlier than in healthy dogs (P = 0.0153). The TTP and RT of the hepatic parenchyma were significantly earlier in extrahepatic-congenital portosystemic shunt dogs than in healthy dogs (P = 0.0018 and P = 0.0024, respectively). ΔHP-PV was significantly shorter in extrahepatic-congenital portosystemic shunt dogs than in healthy dogs (P = 0.0018). CEUS effectively revealed changes in hepatic microvascular perfusion including hepatic artery, portal vein, and hepatic parenchyma simultaneously in extrahepatic-congenital portosystemic shunt dogs. Rapid hepatic artery and hepatic parenchyma enhancements may reflect a compensatory increase in hepatic artery blood flow (arterialization) caused by a decrease in portal vein blood flow and may be used as an additional diagnostic test to distinguish extrahepatic-congenital portosystemic shunt dogs from healthy dogs.
  • Tomoya Morita, Kensuke Nakamura, Tatsuyuki Osuga, Nozomu Yokoyama, Keitaro Morishita, Noboru Sasaki, Hiroshi Ohta, Mitsuyoshi Takiguchi
    American journal of veterinary research 80 1 51 - 60 2019年01月 [査読有り][通常論文]
     
    OBJECTIVE To determine the relationship between acute volume overload and echocardiographic indices of right ventricular (RV) function and dyssynchrony in healthy dogs. ANIMALS 7 healthy Beagles. PROCEDURES Right heart catheterization and echocardiography were performed in 7 healthy anesthetized Beagles at baseline and after induction of volume overload. Volume overload was induced by IV infusion of lactated Ringer solution (150 mL/kg/h for 90 minutes). Echocardiographic indices of RV function, including peak velocity of systolic tricuspid annular motion, tricuspid annulus plane systolic excursion, fractional area change, RV Tei index, RV longitudinal strain (RVLS), and systolic RV longitudinal strain rate (RVLSR), were obtained by use of speckle tracking echocardiography (STE). In addition, SD of the systolic shortening time of the right ventricle for the 6 segments (RV-SD6) was determined with STE. RESULTS Volume overload significantly increased the RV end-diastolic pressure, compared with the baseline value. Echocardiographic indices of RV function, except for septal RVLSR, were significantly enhanced by volume overload. In contrast, RV-SD6 did not change with volume overload. Although echocardiographic indices of RV function, except for septal RVLSR, were correlated with RV end-diastolic pressure, RV-SD6 was not correlated. CONCLUSIONS AND CLINICAL RELEVANCE Echocardiographic indices of RV function, including RVLS and RVLSR, were affected by acute short-term volume overload. Therefore, results for assessment of RV function by use of STE in dogs with clinical conditions associated with right-sided chronic volume overload, such as tricuspid and pulmonic regurgitation, should be interpreted with caution.
  • Osamu Ichii, Hiroshi Ohta, Taro Horino, Teppei Nakamura, Marina Hosotani, Tatsuya Mizoguchi, Keitaro Morishita, Kensuke Nakamura, Noboru Sasaki, Mitsuyoshi Takiguchi, Ryo Sato, Kazuhisa Oyamada, Yaser Hosny Ali Elewa, Yasuhiro Kon
    Frontiers in veterinary science 6 2 - 2 2019年 [査読有り][通常論文]
     
    [This corrects the article DOI: 10.3389/fvets.2018.00289.].
  • Hiroshi Ohta, Kazuki Kojima, Nozomu Yokoyama, Noboru Sasaki, Yumiko Kagawa, Kiwamu Hanazono, Tomohito Ishizuka, Keitaro Morishita, Kensuke Nakamura, Satoshi Takagi, Mitsuyoshi Takiguchi
    Canadian journal of veterinary research = Revue canadienne de recherche veterinaire 82 4 278 - 286 2018年10月 [査読有り][通常論文]
     
    The objective of this study was to examine the effects of immunosuppressive prednisolone therapy on pancreatic tissue and the concentration of serum canine pancreatic lipase immunoreactivity (cPLI) in healthy dogs. Six healthy beagle dogs were subcutaneously administered an immunosuppressive dose of prednisolone [4 mg/kg body weight (BW)] once daily for either 2 or 3 weeks. Serum cPLI concentration was measured before and after treatment. Ultrasonographic examination of the pancreas and laparoscopic biopsy and histopathological examination of the right pancreatic lobe and the liver were also conducted before and after treatment. The expression of pancreatic lipase messenger ribonucleic acid (mRNA) in the pancreas and liver was examined by polymerase chain reaction (PCR). Although the serum cPLI concentration was significantly higher on day 14 and on the day of the second laparoscopy than before treatment, it was classified as normal (≤ 200 μg/L) in 5 dogs and as abnormal (≥ 400 μg/L) in only 1 dog. None of the 6 dogs showed clinical signs of pancreatitis during the study period. After treatment, ultrasonographic examination of the pancreas showed no changes except for a hypoechoic pancreas in 1 dog. Histopathological examination of the right pancreatic lobe in all dogs showed no evidence of pancreatitis after treatment. Pancreatic lipase mRNA expression was detected in the pancreas, but not in the liver, before and after treatment. The administration of 4 mg/kg BW per day of prednisolone for 2 or 3 weeks increased the serum cPLI concentration without clinical signs of pancreatitis, although an abnormal cPLI concentration (≥ 400 μg/L) was observed in only 1 dog. No ultrasonographic or histological evidence of pancreatitis was observed in any of the dogs.
  • 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][通常論文]
     
    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.
  • Sasaoka K, Nakamura K, Osuga T, Morita T, Yokoyama N, Morishita K, Sasaki N, Ohta H, Takiguchi M
    Journal of Veterinary Internal Medicine 32 1 314 - 323 2018年 [査読有り][通常論文]
     
    Background: Transcranial Doppler ultrasound examination (TCD) is a rapid, noninvasive technique used to evaluate cerebral blood flow and is useful for the detection of intracranial hypertension in humans. However, the clinical usefulness of TCD in diagnosing intracranial hypertension has not been demonstrated for intracranial diseases in dogs. Objectives: To determine the association between the TCD variables and intracranial hypertension in dogs with intracranial diseases. Animals: Fifty client-owned dogs with neurologic signs. Methods: Cross-sectional study. All dogs underwent TCD of the basilar artery under isoflurane anesthesia after magnetic resonance imaging (MRI). Dogs were classified into 3 groups based on MRI findings: no structural diseases (group I), structural disease without MRI evidence of intracranial hypertension (group II), and structural disease with MRI evidence of intracranial hypertension (group III). The TCD vascular resistance variables (resistive index [RI], pulsatility index [PI], and the ratio of systolic to diastolic mean velocity [Sm/Dm]) were measured. Results: Fifteen, 22, and 13 dogs were classified into groups I, II, and III, respectively. Dogs in group III had significantly higher Sm/Dm (median, 1.78; range, 1.44–2.58) than those in group I (median, 1.63; range, 1.43–1.75) and group II (median, 1.62; range, 1.27–2.10). No significant differences in RI and PI were identified among groups. Conclusions and Clinical Importance: Our findings suggest that increased Sm/Dm is associated with MRI findings of suspected intracranial hypertension in dogs with intracranial diseases and that TCD could be a useful tool to help to diagnose intracranial hypertension.
  • Osamu Ichii, Hiroshi Ohta, Taro Horino, Teppei Nakamura, Marina Hosotani, Tatsuya Mizoguchi, Keitaro Morishita, Kensuke Nakamura, Noboru Sasaki, Mitsuyoshi Takiguchi, Ryo Sato, Kazuhisa Oyamada, Yaser Hosny Ali Elewa, Yasuhiro Kon
    Frontiers in veterinary science 5 289 - 289 2018年 [査読有り][通常論文]
     
    Increased incidence of kidney disease (KD) is a common concern in human and companion animals. Cats, in particular, are highly susceptible to KD. Novel KD biomarkers would help to address these problems. Therefore, we are focusing on microRNA, a highly conserved nucleic acid, as a KD biomarker for various animals. We previously reported that altered levels of urinary exosome (UExo)-derived microRNAs indicate renal pathologies in dogs. This study comprehensively examined UExo-derived microRNAs, which reflected the KD status in cats. The examined cats were divided into two groups: normal renal function (NR) and KD. Based on our previous data in dogs and cats, as well as the present data on UExo-derived microRNAs in cats by next-generation sequencing, let-7b, let-7f, miR-10a, miR-10b, miR-21a, miR-22, miR-26a, miR-27b, miR-146a, miR-181a, miR-191, and miR-486a were identified as biomarker candidates. In summary, the levels of UExo-derived let-7b, miR-22, and miR-26a significantly decreased in cats with KD from the early stages of the disease. UExo-derived miRNA levels normalized to urinary creatinine or total RNA of miR-21a was significantly higher in the KD group. Importantly, the ratio of UExo-derived miR-21a to let-7b showed a significant and strongest correlation with serum creatinine (ρ = 0.751), blood urea nitrogen (ρ = 0.754), and urinary creatinine (ρ = -0.421) among all examined indices. Further, the ratio of miR-181a to let-7b or miR-10b significantly correlated with the progression of renal dysfunction in the KD group. Thus, we identified that UExo-derived microRNAs in cats, and their raw and normalized levels could indicate altered renal function.
  • Noboru Sasaki, Kazuhiro Ishi, Nobuki Kudo, Shouta M. M. Nakayama, Kensuke Nakamura, Keitaro Morishita, Hiroshi Ohta, Mayumi Ishizuka, Mitsuyoshi Takiguchi
    PLOS ONE 12 11 e0188093  2017年11月 [査読有り][通常論文]
     
    Non-muscle invasive bladder cancer is one of the most common tumors of the urinary tract. Despite the current multimodal therapy, recurrence and progression of disease have been challenging problems. We hereby introduced a new approach, ultrasound-assisted intravesical chemotherapy, intravesical instillation of chemotherapeutic agents and microbubbles followed by ultrasound exposure. We investigated the feasibility of the treatment for nonmuscle invasive bladder cancer. In order to evaluate intracellular delivery and cytotoxic effect as a function to the thickness, we performed all experiments using a bladder cancer mimicking 3D culture model. Ultrasound-triggered microbubble cavitation increased both the intracellular platinum concentration and the cytotoxic effect of cisplatin at the thickness of 70 and 122 mu m of the culture model. The duration of enhanced cytotoxic effect of cisplatin by ultrasound-triggered microbubble cavitation was approximately 1 hr. Based on the distance and duration of delivery, we further tested the feasibility of repetition of the treatment. Triple treatment increased the effective distance by 1.6-fold. Our results clearly showed spatial and temporal profile of delivery by ultrasound-triggered microbubble cavitation in a tumor-mimicking structure. Furthermore, we demonstrated that the increase in intracellular concentration results in the enhancement of the cytotoxic effect in a structure with the certain thickness. Repetition of ultrasound exposure would be treatment of choice in future clinical application. Our results suggest ultrasound-triggered microbubble cavitation can be repeatable and is promising for the local control of non-muscle invasive bladder cancer.
  • Nisa K, Lim SY, Shinohara M, Nagata N, Sasaoka K, Dermlim A, Leela-Arporn R, Morita T, Yokoyama N, Osuga T, Sasaki N, Morishita K, Nakamura K, Ohta H, Takiguchi M
    The Journal of Veterinary Medical Science 79 9 1585 - 1590 2017年09月 [査読有り][通常論文]
  • Tomoya Morita, Kensuke Nakamura, Tatsuyuki Osuga, Nozomu Yokoyama, Keitaro Morishita, Noboru Sasaki, Hiroshi Ohta, Mitsuyoshi Takiguchi
    ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES 34 7 1040 - 1049 2017年07月 [査読有り][通常論文]
     
    Background: The assessment of hemodynamic change by echocardiography is clinically useful in patients with pulmonary hypertension. Recently, mild elevation of the mean pulmonary arterial pressure (PAP) has been shown to be associated with increased mortality. However, changes in the echocardiographic indices of right ventricular (RV) function are still unknown. The objective of this study was to validate the relationship between echocardiographic indices of RV function and right heart catheterization variables under a mild RV pressure overload condition. Methods and Results: Echocardiography and right heart catheterization were performed in dog models of mild RV pressure overload induced by thromboxane A(2) analog (U46619) (n=7). The mean PAP was mildly increased (19.3 +/- 1.1mm Hg), and the cardiac index was decreased. Most echocardiographic indices of RV function were significantly impaired even under a mild RV pressure overload condition. Multivariate analysis revealed that the RV free wall longitudinal strain (RVLS), standard deviation of the time-to-peak longitudinal strain of RV six segments (RV-SD) by speckle-tracking echocardiography, and Tei index were independent echocardiographic predictors of the mean PAP (free wall RVLS, beta=-0.60, P<.001; RV-SD, beta=0.40, P=.011), pulmonary vascular resistance (free wall RVLS, beta=-0.39, P=.020; RV-SD, beta=0.47, P=.0086; Tei index, beta=0.34, P=.047), and cardiac index (Tei index, beta=-0.65, P<.001). Conclusions: Free wall RVLS, RV-SD, and Tei index are useful for assessing the hemodynamic change under a mild RV pressure overload condition.
  • 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][通常論文]
     
    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-1 beta, IL-6, IL-8 and TNF-alpha) 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-alpha mRNA expression in the TLR2-or TLR4-stimulated colorectal samples, and IL-1 beta 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.
  • K. Morishita, A. Hiramoto, A. Michishita, S. Takagi, T. Osuga, S. Y. Lim, K. Nakamura, N. Sasaki, H. Ohta, M. Takiguchi
    JOURNAL OF VETERINARY INTERNAL MEDICINE 31 3 770 - 777 2017年05月 [査読有り][通常論文]
     
    Background: Perflubutane microbubbles, a second-generation ultrasound contrast agent, are phagocytized by Kupffer cells. This characteristic may be useful to differentiate diffuse hepatic diseases in dogs. Hypothesis/objectives: To determine whether the washout ratio in the hepatic vein (HV) measured by contrast-enhanced ultrasonography (CEUS) can distinguish between inflammatory and noninflammatory hepatic disorders in dogs. Animals: Forty-one client-owned dogs with hepatic disorders including 14 with hepatitis, 7 with primary hypoplasia of the portal vein (PHPV), 9 with congenital portosystemic shunt (cPSS), and 11 with other hepatopathy were enrolled. Six dogs without hepatic disease also were evaluated as healthy controls. Methods: Dogs with hepatic disorders were prospectively included. Contrast-enhanced ultrasonography of the HV was performed for 2 minutes. Washout ratio was defined as the attenuation rate from peak intensity to the intensity at the end of the CEUS study. Results: Washout ratio in the hepatitis group (median, 18.0%; range, 2.0-37.0%) was significantly lower than that of the PHPV (median, 52.2%; range, 11.5-86.3%), cPSS (median, 60.0%; range, 28.6-77.4%), other hepatopathy (median, 70.5%; range, 26.6-88.4%), and normal (median, 78.0%; range, 60.7-91.7%) groups. The area under the receiver operating characteristic curve for hepatitis was 0.960, with a 95% confidence interval (CI) of 0.853-0.990. Washout ratio <= 37.1% resulted in a sensitivity of 100% (95% CI, 78.5-100%) and specificity of 85.2% (95% CI, 67.5-94.1%) for the prediction of hepatitis. Conclusions and Clinical Importance: Washout ratio can distinguish hepatitis from the other noninflammatory disorders with high accuracy. This result might reflect impaired Kupffer cell phagocytosis in dogs with hepatitis.
  • Yoshimi Iwaki, Satoshi Takagi, Keitaro Morishita, Kiwamu Hanazono, Kenji Hosoya, Masahiro Okumura
    JAPANESE JOURNAL OF VETERINARY RESEARCH 65 2 95 - 99 2017年05月 [査読有り][通常論文]
     
    A 10-year-old, spayed female dog with intermittent coughing and respiratory distress was presented at our hospital. Thoracic radiographs revealed a 71 x 43 mm intrathoracic solitary mass. After one week, coughing worsened and pleural effusion was found. The intrathoracic mass had the same intensity as the liver in contrast-enhanced computed tomography images. There were no signs of diaphragmatic hernia, and attachment of the mass to the diaphragm and the caudal vena cava was observed during surgery. Histopathologically, the mass was composed of normal hepatic parenchyma, and based on this finding and the gross findings, it was diagnosed as an ectopic liver. Owing to its location, the ectopic liver may have caused regional venous occlusion, which resulted in the clinical symptoms observed.
  • K. Morishita, A. Hiramoto, A. Michishita, S. Takagi, T. Osuga, S. Y. Lim, K. Nakamura, N. Sasaki, H. Ohta, M. Takiguchi
    Journal of Veterinary Internal Medicine 31 3 770 - 777 2017年05月01日 [査読有り][通常論文]
     
    Background: Perflubutane microbubbles, a second-generation ultrasound contrast agent, are phagocytized by Kupffer cells. This characteristic may be useful to differentiate diffuse hepatic diseases in dogs. Hypothesis/objectives: To determine whether the washout ratio in the hepatic vein (HV) measured by contrast-enhanced ultrasonography (CEUS) can distinguish between inflammatory and noninflammatory hepatic disorders in dogs. Animals: Forty-one client-owned dogs with hepatic disorders including 14 with hepatitis, 7 with primary hypoplasia of the portal vein (PHPV), 9 with congenital portosystemic shunt (cPSS), and 11 with other hepatopathy were enrolled. Six dogs without hepatic disease also were evaluated as healthy controls. Methods: Dogs with hepatic disorders were prospectively included. Contrast-enhanced ultrasonography of the HV was performed for 2 minutes. Washout ratio was defined as the attenuation rate from peak intensity to the intensity at the end of the CEUS study. Results: Washout ratio in the hepatitis group (median, 18.0% range, 2.0–37.0%) was significantly lower than that of the PHPV (median, 52.2% range, 11.5–86.3%), cPSS (median, 60.0% range, 28.6–77.4%), other hepatopathy (median, 70.5% range, 26.6–88.4%), and normal (median, 78.0% range, 60.7–91.7%) groups. The area under the receiver operating characteristic curve for hepatitis was 0.960, with a 95% confidence interval (CI) of 0.853–0.990. Washout ratio ≤37.1% resulted in a sensitivity of 100% (95% CI, 78.5–100%) and specificity of 85.2% (95% CI, 67.5–94.1%) for the prediction of hepatitis. Conclusions and Clinical Importance: Washout ratio can distinguish hepatitis from the other noninflammatory disorders with high accuracy. This result might reflect impaired Kupffer cell phagocytosis in dogs with hepatitis.
  • Keitaro Morishita, Akira Hiramoto, Asuka Michishita, Satoshi Takagi, Yuki Hoshino, Takaharu Itami, Sue Yee Lim, Tatsuyuki Osuga, Sayuri Nakamura, Kenji Ochiai, Kensuke Nakamura, Hiroshi Ohta, Masahiro Yamasaki, Mitsuyoshi Takiguchi
    AMERICAN JOURNAL OF VETERINARY RESEARCH 78 4 465 - 471 2017年04月 [査読有り][通常論文]
     
    OBJECTIVE To assess the use of contrast-enhanced ultrasonography (CEUS) of the hepatic vein for the detection of hemodynamic changes associated with experimentally induced portal hypertension in dogs. ANIMALS 6 healthy Beagles. PROCEDURES A prospective study was conducted. A catheter was surgically placed in the portal vein of each dog. Hypertension was induced by intraportal injection of microspheres (10 to 15 mg/kg) at 5-day intervals via the catheter. Microsphere injections were continued until multiple acquired porto-systemic shunts were created. Portal vein pressure (PVP) was measured through the catheter. Contrast-enhanced ultrasonography was performed before and after establishment of hypertension. Time-intensity curves were generated from the region of interest in the hepatic vein. Perfusion variables measured for statistical analysis were hepatic vein arrival time, time to peak, time to peak phase (TTPP), and washout ratio. The correlation between CEUS variables and PVP was assessed by use of simple regression analysis. RESULTS Time to peak and TTPP were significantly less after induction of portal hypertension. Simple regression analysis revealed a significant negative correlation between TTPP and PVP. CONCLUSIONS AND CLINICAL RELEVANCE CEUS was useful for detecting hemodynamic changes associated with experimentally induced portal hypertension in dogs, which was characterized by a rapid increase in the intensity of the hepatic vein. Furthermore, TTPP, a time-dependent variable, provided useful complementary information for predicting portal hypertension. IMPACT FOR HUMAN MEDICINE Because the method described here induced presinusoidal portal hypertension, these results can be applied to idiopathic portal hypertension in humans.
  • Nozomu Yokoyama, Hiroshi Ohta, Yumiko Kagawa, Rommaneeya Leela-Arporn, Angkhana Dermlim, Khoirun Nisa, Tomoya Morita, Tatsuyuki Osuga, Noboru Sasaki, Keitaro Morishita, Kensuke Nakamura, Mitsuyoshi Takiguchii
    JOURNAL OF VETERINARY MEDICAL SCIENCE 79 3 456 - 463 2017年03月 [査読有り][通常論文]
     
    We examine the expression of tight junction and adherence junction proteins in the colorectal mucosa of miniature dachshunds (MDs) with inflammatory colorectal polyps (ICRPs). Colorectal mucosa samples were endoscopically obtained from 8 MDs with ICRPs and 8 control dogs for immunoblotting. Paraffin-embedded tissues of surgically resected inflamed lesions from another 5 MDs with ICRPs and full-thickness colorectal specimens from 5 healthy beagles were obtained for immunohistochemistry. The expression patterns of claudin-1, -2, -3, -4, -5, -7 and -8, E-cadherin and beta-catenin were analyzed in the non(-)inflamed mucosa and inflamed mucosa of ICRPs and colorectal mucosa of control dogs by immunoblotting.The localization of these proteins in the inflamed lesions was analyzed by immunohistochemistry. The expressions of each of claudin, E-cadherin and beta-catenin were not significantly different between control dogs and non inflamed colonic mucosa from MDs with ICRPs. In contrast, only E-cadherin and beta-catenin were detected in the inflamed lesions of MDs with 1CRPs. By immunohistochemistry, claudin-2, -3, -4, -5 and -7, E-cadherin and beta-catenin were expressed in the colorectal epithelium within the inflamed mucosa, but not in granulation tissue. Distributions of claudin-2, -3, -4, -5, and -7, E-cadherin and beta-catenin in the colonic epithelium were not different between MDs with ICRPs and control dogs. These results indicated that no significant alteration was detected in several tight junction or adherence junction proteins expression in the colorectal epithelium of ICRPs.
  • Ohta H, Morita T, Yokoyama N, Osuga T, Sasaki N, Morishita K, Nakamura K, Takiguchi M
    Journal of Small Animal Practice 58 6 342 - 347 2017年 [査読有り][通常論文]
     
    Objectives: In this pilot study, serum canine pancreatic lipase immunoreactivity was measured repeatedly in dogs with various immune-mediated diseases that were treated with immunosuppressive doses of prednisolone. Methods: Ten client-owned dogs with newly diagnosed immune-mediated disease that had normal canine pancreatic lipase immunoreactivity concentrations (≤200 µg/l) were treated with 2 to 2.2 mg/kg prednisolone orally once daily as the initial treatment. Serum samples were obtained from each of the dogs prior to treatment and at 1- to 4-week intervals during immunosuppressive treatment. The highest canine pancreatic lipase immunoreactivity concentration detected during immunosuppressive treatment was defined as the peak canine pancreatic lipase immunoreactivity. Results: Peak canine pancreatic lipase immunoreactivity concentrations were classified as normal in two dogs, questionable (201 to 399 µg/l) in three dogs, and abnormal (≥400 µg/l) in five dogs. Peak canine pancreatic lipase immunoreactivity concentrations were significantly higher than baseline canine pancreatic lipase immunoreactivity concentrations but there was no evidence of clinical pancreatitis. Clinical Significance: It remains unclear whether the five of 10 dogs with elevated canine pancreatic lipase immunoreactivity during prednisone treatment had subclinical pancreatitis or whether the abnormal results were a consequence of prednisolone administration.
  • Yokoyama N, Ohta H, Yamazaki J, Kagawa Y, Ichii O, Khoirun N, Morita T, Osuga T, Lim S.Y, Sasaki N, Morishita K, Nakamura K, Takiguchi M
    Journal of Comparative Pathology 156 2-3 183 - 190 2017年 [査読有り][通常論文]
     
    Inflammatory colorectal polyps (ICRPs) are characterized by the formation of multiple or solitary polyps with marked neutrophil infiltration in the colorectal area, and are speculated to be a novel form of breed-specific canine idiopathic inflammatory bowel disease (IBD). In human IBD, toll-like receptor (TLR) 2 and TLR4 have been reported to be involved in the pathogenesis of the disease. The aim of this study was to evaluate the expression of TLR2 and TLR4 mRNA in the colorectal mucosa of dogs with ICRPs by in-situ hybridization using an RNAscope assay. Samples of inflamed colorectal mucosa (n = 5) and non-inflamed mucosa (n = 5) from miniature dachshunds (MDs) with ICRPs and colonic mucosa from healthy beagles (n = 5) were examined. TLR2 and TLR4 hybridization signals were localized to the colorectal epithelium, inflammatory cells and fibroblasts in the inflamed colorectal mucosa of affected dogs. The signals were significantly greater in inflamed colorectal epithelium compared with non-inflamed epithelium of MDs with ICRPs and healthy beagles (P <0.05). These results suggest that increased expression of TLR2 and TLR4 mRNA in the inflamed colorectal mucosa results from not only inflammatory cell infiltration, but also the upregulation of TLR2 and TLR4 mRNA in the colonic epithelium.
  • Nakamura K, Kawamoto S, Osuga T, Morita T, Sasaki N, Morishita K, Ohta H, Takiguchi M
    Journal of Veterinary Internal Medicine 31 2 316 - 325 2017年 [査読有り][通常論文]
  • Morita T, Nakamura K, Osuga T, Yokoyama N, Khoirun N, Morishita K, Sasaki N, Ohta H, Takiguchi M
    Journal of Veterinary Cardiology 19 4 351 - 362 2017年 [査読有り][通常論文]
     
    Introduction To assess the repeatability and characteristics of echocardiographic indices of the right ventricular (RV) function derived from speckle-tracking echocardiography. Animals Fourteen laboratory Beagles and 103 privately owned dogs without cardiac disease were involved in this study. Materials and methods Right ventricular longitudinal strain, strain rate, and a strain-related index for assessing RV dyssynchrony derived from speckle-tracking echocardiography were obtained by two different observers using five Beagles. Within-day, between-day, and interobserver coefficients of variation and the intraclass correlation coefficient of speckle-tracking echocardiography indices were determined. Both speckle-tracking echocardiography and conventional indices of RV function, including the peak velocity of systolic tricuspid annular motion, tricuspid annulus plane systolic excursion, fractional area change, and the Tei index, were obtained from 14 Beagles and 103 privately owned dogs. Relationships between echocardiographic indices and the body weight, heart rate, age, and sex were estimated by regression analysis. Results Speckle-tracking echocardiographic indices showed good within-day repeatability, between-day and interobserver repeatability were moderate to good. In large dogs, RV longitudinal strain, strain rate, and fractional area change were significantly decreased, while the index of RV dyssynchrony, systolic tricuspid annular motion, tricuspid annulus plane systolic excursion, and the Tei index were increased. All speckle-tracking and conventional echocardiographic indices were correlated with the body weight. Discussion and conclusions The speckle-tracking echocardiography indices were highly repeatable and body weight affected speckle-tracking echocardiography indices in dogs. Further studies are needed to apply speckle-tracking echocardiography indices in dogs with cardiac disease.
  • Osamu Ichii, Hiroshi Ohta, Taro Horino, Teppei Nakamura, Marina Hosotani, Tatsuya Mizoguchi, Keitaro Morishita, Kensuke Nakamura, Yuki Hoshino, Satoshi Takagi, Noboru Sasaki, Mitsuyoshi Takiguchi, Ryo Sato, Kazuhisa Oyamada, Yasuhiro Kon
    SCIENTIFIC REPORTS 7 40340  2017年01月 [査読有り][通常論文]
     
    MicroRNAs act as post-transcriptional regulators, and urinary exosome (UExo)-derived microRNAs may be used as biomarkers. Herein, we screened for UExo-derived microRNAs reflecting kidney disease (KD) status in dogs. Examined dogs were divided into healthy kidney control (HC) and KD groups according to renal dysfunction. We confirmed the appearance of UExo having irregular globe-shapes in a dog by immunoblot detection of the exosome markers, TSG101 and CD9. Based on our previous data using KD model mice and the data obtained herein by next generation sequencing of UExo-derived microRNAs in dogs, miR-26a, miR-146a, miR-486, miR-21a, and miR-10a/b were selected as candidate microRNAs. In particular, UExo-derived miR-26a and miR-10a/b were significantly decreased in KD dogs, and miR-26a levels negatively correlated with deteriorated renal function compared to the other miRNAs. UExo-derived miR-21a levels corrected or not to that of internal control microRNAs in UExo, miR-26a and miR-191, significantly increased with renal dysfunction. In kidney tissues, the decrease of miR-26a and miR-10a/ b in the glomerulus and miR-10b in the tubulointerstitium negatively correlated with deteriorated renal function and histopathology. Increased miR-21a in the tubulointerstitium rather than in the glomerulus correlated with deteriorated renal histopathology. In conclusion, microRNAs reflecting the changes in renal function and histopathology in dogs were identified in this study.
  • Keitaro Morishita, Akira Hiramoto, Tatsuyuki Osuga, Sue Yee Lim, Nisa Khoirun, Noboru Sasaki, Kensuke Nakamura, Hiroshi Ohta, Masahiro Yamasaki, Mitsuyoshi Takiguchi
    JOURNAL OF VETERINARY MEDICAL SCIENCE 78 12 1753 - 1758 2016年12月 [査読有り][通常論文]
     
    Contrast-enhanced ultrasonography (CEUS) of the hepatic vein can assess intrahepatic hemodynamic changes and has been studied as a noninvasive method to assess the severity of portal hypertension and hepatic fibrosis in humans. However, few reports have described its usefulness in veterinary medicine. The purpose of this study was to characterize CEUS findings of the hepatic vein in normal dogs and assess the repeatability of this method both in a conscious group (n=6) and a sedated group (n=6). Sonazoid (R) (0.01 ml/kg) was used as a contrast agent, and scanning of the hepatic vein was performed for 2 min. Time-intensity curves were generated from regions of interest in the hepatic vein. Four perfusion parameters were measured for quantitative analysis: hepatic vein arrival time (HVAT), time to peak (TTP), time to peak phase (TTPP) and wash-out ratio (WR). CEUS examinations were performed three times in each dog. The median (range) values of HVAT, TTP, TTPP and WR in the conscious group were 13.5 sec (9-22 sec), 12.5 sec (6-24 sec), 8 sec (6-13 sec) and 78.0% (60.7-91.7%), respectively. Median (range) values of HVAT, TTP, TTPP and WR in the sedated group were 12 sec (8-17 sec), 12.5 sec (9-17 sec), 9 sec (7-13 sec) and 84.1% (63.0-94.4%), respectively. The coefficients of variation of these parameters in the conscious and sedated groups were 7.6-29.7% and 11.8-14.8%, respectively.
  • Tatsuyuki Osuga, Kensuke Nakamura, Tomoya Morita, Khoirun Nisa, Nozomu Yokoyama, Noboru Sasaki, Keitaro Morishita, Hiroshi Ohta, Mitsuyoshi Takiguchi
    AMERICAN JOURNAL OF VETERINARY RESEARCH 77 9 952 - 960 2016年09月 [査読有り][通常論文]
     
    OBJECTIVE To elucidate the relationship between acute volume overload and left atrial phasic function in healthy dogs. ANIMALS 6 healthy Beagles. PROCEDURES Dogs were anesthetized. A Swan-Ganz catheter was placed to measure mean pulmonary capillary wedge pressure (PCWP). Cardiac preload was increased by IV infusion with lactated Ringer solution at 150 mL/kg/h for 90 minutes. Transthoracic echocardiography was performed before (baseline) and at 15, 30, 45, 60, 75, and 90 minutes after volume loading began. At each echocardiographic assessment point, apical 4-chamber images were recorded and analyzed to derive time-left atrial area curves. Left atrial total (for reservoir function), passive (for conduit function), and active (for booster-pump function) fractional area changes were calculated from the curves. RESULTS Volume overload resulted in a significant increase from baseline in PCWP from 15 to 90 minutes after volume loading began. All fractional area changes at 15 to 90 minutes were significantly increased from baseline. In multiple regression analysis, quadratic regression models were better fitted to the relationships between PCWP and each of the total and active fractional area changes than were linear regression models. A linear regression model was better fitted to the relationship between PCWP and passive fractional area change. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that left atrial phasic function assessed on the basis of left atrial phasic areas was enhanced during experimental cardiac volume loading in healthy dogs. The effect of volume load should be considered when evaluating left atrial phasic function by indices derived from left atrial phasic sizes.
  • 犬の免疫介在性関節炎の疫学的および臨床的特徴
    永田 矩之, 中村 健介, 森下 啓太郎, 越後 良介, 奥村 正裕, 佐々木 東, 大田 寛, 滝口 満喜
    北海道獣医師会雑誌 60 8 416 - 416 (公社)北海道獣医師会 2016年08月
  • Kensuke Nakamura, Nobuo Tohyama, Masahiro Yamasaki, Hiroshi Ohta, Keitaro Morishita, Mitsuyoshi Takiguchi
    JOURNAL OF THE AMERICAN ANIMAL HOSPITAL ASSOCIATION 52 4 256 - 258 2016年07月 [査読有り][通常論文]
     
    A miniature dachshund male with severe azotemia of unknown cause was referred. Serum biochemistry revealed severe azotemia and hypercalcemia, but serum intact parathormone and parathormone-related protein were normal. Although the owner reported that the dog had never ingested any drugs or supplements, it was revealed that the owner's son used antipsoriatic ointment, maxacalcitol, which contained an active vitamin D-3 analogue, daily and the dog often ate the son's dander and licked his skin, especially after he applied the maxacalcitol ointment. After the dog was insulated from the maxacalcitol ointment and the son as much as possible, the hypercalcemia and azotemia improved gradually and had mostly resolved at 3 mo. The dog has been generally free of clinical signs without any treatment for over 2 yr.
  • Tomoya Morita, Kensuke Nakamura, Tatsuyuki Osuga, Sue Yee Lim, Nozomu Yokoyama, Keitaro Morishita, Hiroshi Ohta, Mitsuyoshi Takiguchi
    AMERICAN JOURNAL OF VETERINARY RESEARCH 77 7 715 - 720 2016年07月 [査読有り][通常論文]
     
    OBJECTIVE To evaluate repeatability and reproducibility of right ventricular Tei index (RTX) values derived from dual pulsed-wave Doppler, conventional pulsed-wave Doppler, and tissue Doppler echocardiography and to investigate relationships and repeatability among the 3 methods in healthy dogs. ANIMALS 6 healthy adult Beagles. PROCEDURE Echocardiography was performed on each dog on different days for 2 weeks (3 times/d) by 2 echocardiographers. Intraobserver within- and between-day and interobserver coefficients of variation (CVs) and intraclass correlation coefficients (ICCs) for RTXs derived from dual pulse-waved Doppler (RTXDPD), conventional pulsed-wave Doppler (RTXPD), and tissue Doppler (RTXTD) methods were determined. Degrees of agreement among RTX values derived from the 3 methods were assessed by modified Bland-Altman analysis. RESULTS Least squares mean (95% confidence interval) RTXTD was 0.50 (0.46 to 0.54), which was significantly higher than that for RTXDPD (0.27 [0.23 to 0.31]) and RTXPD (0.25 [0.21 to 0.29]). Agreement between RTXDPD and RTXPD was good (bias [mean difference], 0.04 [95% confidence interval, -0.03 to 0.10]). The RTXDPD had high within-day (CV, 6.1; ICC, 0.77) and interobserver (CV, 3.5; ICC, 0.83) repeatability, but between-day repeatability was not high. The RTXTD had high within-day repeatability (CV, 6.0; ICC, 0.80), but between-day and interobserver repeatability were not high. Within-day, between-day, and interobserver repeatability of RTXPD were not high. CONCLUSIONS AND CLINICAL RELEVANCE RTXDPD measurement was a repeatable and reproducible method of cardiac evaluation in healthy dogs. The RTXTD values were significantly higher than the RTXDPD and RTXPD values; therefore, RTX values derived from different echocardiographic methods should be interpreted with caution.
  • ソマトトロピン産生性下垂体腫瘍によりインスリン抵抗性を呈した糖尿病の猫の1例
    和泉 雄介, 細谷 謙治, 早川 小百合, 森下 啓太郎, 高木 哲, 奥村 正裕
    日本獣医師会雑誌 69 5 293 - 293 (公社)日本獣医師会 2016年05月
  • Nakamura K, Morita T, Osuga T, Morishita K, Sasaki N, Ohta H, Takiguchi M
    Journal of Veterinary Internal Medicine 30 1 69 - 75 Wiley-Blackwell 2016年 [査読有り][通常論文]
     
    Background: The right ventricular (RV) Tei index (TX) has a significant correlation with the severity of pulmonary hypertension. However, the role of RV dysfunction in dogs with myxomatous mitral valvular heart disease (MMVD) has not been addressed. Objectives: To investigate the correlation between right ventricular Tei-index (RVTX) and the prognosis for dogs with MMVD. Animals: Thirty client-owned dogs with MMVD. Methods: Clinical cohort study. Dogs were divided into two groups on the basis of the onset of cardiac-related death within 1 year of the first echocardiographic examination. Physical examination and echocardiographic variables were compared between the groups. Receiver operating characteristic (ROC) curves and multivariate logistic analysis were used to assess the comparative accuracy when identifying dogs with cardiac-related death. Results: The highest accuracy was obtained for RVTX with an area under the ROC curve (AUC) of 0.95 (95% confidence interval [CI] 0.81-0.99) followed by the left atrial to aortic root ratio with an AUC of 0.91 (95% CI 0.74-0.98), peak early diastolic mitral inflow velocity with an AUC of 0.84 (95% CI 0.64-0.94), and Doppler estimates of systolic pulmonary artery pressure with an AUC of 0.84 (95% CI 0.61-0.95). According to the multivariate logistic regression analysis, RVTX was the only independent correlate of cardiac-related death within 1 year. Conclusions and Clinical Importance: Right ventricular Tei-index has a strong correlation with the prognosis for dogs with MMVD. The most significant independent predictor of death was RVTX in this study.
  • 猫の尿管結石・閉塞23例における内科療法の反応と外科手術法の検討
    星 清貴, 高木 哲, 細谷 謙次, 星野 有希, 中村 健介, 森下 啓太郎, 金 尚昊, 奥村 正裕
    日本獣医麻酔外科学雑誌 46 Suppl.2 227 - 227 (一社)日本獣医麻酔外科学会 2015年12月
  • ソマトトロピン産生性下垂体腫瘍によりインスリン抵抗性を呈した糖尿病の猫の1例
    和泉 雄介, 細谷 謙次, 早川 小百合, 森下 啓太郎, 華園 究, 星野 有希, 高木 哲, 金 尚昊, 奥村 正裕
    北海道獣医師会雑誌 59 8 394 - 394 (公社)北海道獣医師会 2015年08月
  • Tatsuyuki Osuga, Kensuke Nakamura, Tomoya Morita, Sue Yee Lim, Nozomu Yokoyama, Keitaro Morishita, Hiroshi Ohta, Mitsuyoshi Takiguchi
    AMERICAN JOURNAL OF VETERINARY RESEARCH 76 8 702 - 709 2015年08月 [査読有り][通常論文]
     
    OBJECTIVE To evaluate the effects of dobutamine, esmolol, milrinone, and phenylephrine on left atrial phasic function of healthy dogs. ANIMALS 9 healthy Beagles. PROCEDURES Following sedation with propofol on each of 4 experimental days, dogs were administered a constant rate infusion of dobutamine (5 mu g/kg/min), esmolol (500 mu g/kg/min), milrinone (25 mu g/kg, IV bolus, followed by 0.5 mu g/kg/min), or phenylephrine (2 mu g/kg/min). There was at least a 14-day interval between experimental days. Each drug was administered to 6 dogs. Conventional and 2-D speckle tracking echocardiography were performed before (baseline) and after administration of the cardiovascular drug, and time-left atrial area curves were derived to calculate indices for left atrial reservoir, conduit, and booster pump functions (left atrial phasic function) and left ventricular contractility and lusitropy. RESULTS Compared with baseline values, indices for left atrial reservoir and booster pump functions and left ventricular contractility and lusitropy were significantly increased following dobutamine administration; indices for left atrial phasic function and left ventricular lusitropy were changed insignificantly, and indices for left ventricular contractility were significantly impaired following esmolol administration; indices for left atrial phasic function and left ventricular relaxation were changed insignificantly, and indices for left ventricular systolic function were significantly augmented following milrinone administration; and indices for left atrial phasic function and left ventricular lusitropy were changed insignificantly, and indices of ventricular contractility were significantly impaired following phenylephrine administration. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that, following administration of dobutamine, esmolol, milrinone, or phenylephrine to healthy dogs, left atrial phasic function indices were fairly stable and did not parallel changes in left ventricular function indices.
  • Dynamic CTによる肝細胞性腫瘤の良悪性鑑別
    那須 香菜子, 中村 健介, 高木 哲, 細谷 謙次, 華園 究, 賀川 由美子, 森下 啓太郎, 滝口 満喜
    日本獣医麻酔外科学雑誌 46 Suppl.1 302 - 302 (一社)日本獣医麻酔外科学会 2015年06月
  • 胸水貯留を認めた胸腔内異所性肝の犬の1例
    岩木 芳美, 高木 哲, 森下 啓太郎, 高瀬 奈美, 華園 究, 細谷 謙次, 奥村 正裕
    日本獣医麻酔外科学雑誌 46 Suppl.1 228 - 228 (一社)日本獣医麻酔外科学会 2015年06月
  • Osuga T, Nakamura K, Morita T, Lim S.Y, Nisa K, Yokoyama N, Sasaki N, Morishita K, Ohta H, Takiguchi M
    Journal of Veterinary Internal Medicine 29 6 1518 - 1523 2015年 [査読有り][通常論文]
     
    Background: In humans with heart disease, vitamin D deficiency is associated with disease progression and a poor prognosis. A recent study showed that serum 25-hydroxyvitamin D [25(OH)D] concentration, the hallmark of vitamin D status, was lower in dogs with heart failure than in normal dogs, and a low concentration was associated with poor outcome in dogs with heart failure. Objectives: To elucidate the vitamin D status of dogs with chronic valvular heart disease (CVHD) at different stages of disease severity. Animals: Forty-three client-owned dogs with CVHD. Methods: In this cross-sectional study, dogs were divided into 3 groups (14 dogs in Stage B1, 17 dogs in Stage B2, and 12 dogs in Stage C/D) according to ACVIM guidelines. Dogs underwent clinical examination including echocardiography. Serum 25(OH)D concentrations were measured in each dog. Results: Serum 25(OH)D concentration was significantly lower in Stage B2 (median, 33.2 nmol/L; range, 4.9-171.7 nmol/L) and C/D (13.1 nmol/L; 4.9-58.1 nmol/L) than in Stage B1 (52.5 nmol/L; 33.5-178.0 nmol/L) and was not significantly different between Stage B2 and Stage C/D. Among clinical variables, there were significant negative correlations between 25(OH)D concentration and both left atrial-to-aortic root ratio and left ventricular end-diastolic diameter normalized for body weight. Conclusions and Clinical Importance: These results indicate that vitamin D status is associated with the degree of cardiac remodeling, and the serum 25(OH)D concentration begins to decrease before the onset of heart failure in dogs with CVHD.
  • S. Y. Lim, K. Nakamura, K. Morishita, N. Sasaki, M. Murakami, T. Osuga, N. Yokoyama, H. Ohta, M. Yamasaki, M. Takiguchi
    JOURNAL OF VETERINARY INTERNAL MEDICINE 29 1 71 - 78 2015年01月 [査読有り][通常論文]
     
    Background: Quantitative contrast-enhanced ultrasonography ( CEUS) can detect pancreatic perfusion changes in experimentally induced canine pancreatitis. However, its usefulness in detecting perfusion changes in naturally occurring pancreatitis is unclear. Hypothesis/ Objectives: To determine the feasibility of using CEUS to detect pancreatic and duodenal perfusion changes in naturally occurring canine pancreatitis. Animals: Twenty-three client-owned dogs with pancreatitis, 12 healthy control dogs. Methods: Dogs diagnosed with pancreatitis were prospectively included. CEUS of the pancreas and duodenum were performed. Time-intensity curves were created from regions of interest in the pancreas and duodenum. Five perfusion parameters were obtained for statistical analyses: time to initial up-slope, peak time ( Tp), time to wash-out ( TTW), peak intensity ( PI), and area under the curve ( AUC). Results: For the pancreas, Tp of the pancreatitis group was prolonged when compared to controls ( 62 +/- 11 seconds versus 39 +/- 13 seconds; P <.001). TTW also was prolonged but not significantly ( 268 +/- 69 seconds versus 228 +/- 47 seconds; P =.47). PI and AUC were increased when compared to controls ( 95 +/- 15 versus 78 +/- 13 MPV; P =.009 and 14,900 +/- 3,400 versus 11,000 +/- 2,800 MPV* s; P =.013, respectively). For the duodenum, PI and AUC were significantly increased in the pancreatitis group when compared to controls. Conclusions and Clinical Importance: Contrast-enhanced ultrasonography can detect pancreatic perfusion changes in naturally occurring canine pancreatitis characterized by delayed peak with prolonged hyperechoic enhancement of the pancreas on CEUS. Additionally, duodenal perfusion changes secondary to pancreatitis were observed.
  • Kensuke Nakamura, Sue-Yee Lim, Kenji Ochiai, Masahiro Yamasaki, Hiroshi Ohta, Keitaro Morishita, Satoshi Takagi, Mitsuyoshi Takiguchi
    VETERINARY RADIOLOGY & ULTRASOUND 56 1 55 - 62 2015年01月 [査読有り][通常論文]
     
    Abdominal ultrasonography is one of the most common diagnostic imaging modalities used for dogs with suspected insulinoma; however, pancreatic masses are clearly identified in fewer than half of affected dogs and benign pancreatic nodules can be difficult to differentiate from malignant ones. The purpose of this prospective study was to describe contrast-enhanced ultrasonography (CEUS) characteristics of confirmed pancreatic insulinoma in a group of dogs. Inclusion criteria were as follows: (1) repeated hypoglycemia (blood glucose levels <60 mg/dl, twice or more); (2) elevated blood insulin levels with hypoglycemia; (3) pancreatic nodules detected with conventional ultrasonography; and (4) histological confirmation of pancreatic islet cell carcinoma. Immediately following conventional ultrasonography of the entire abdomen, CEUS of the pancreatic nodule and adjacent parenchyma was performed using contrast-specific technology pulse inversion imaging and perflubutane microbubble contrast agent. Three dogs met inclusion criteria. Pancreatic nodules in all the three dogs became more clearly demarcated after injection of the contrast agent. Each nodule showed different enhancement patterns: markedly hyperechoic for 5 s, slightly hyperechoic for 1 s, and clearly hypoechoic for over 30 s. These results were not in complete agreement with previously reported CEUS findings in human patients with insulinoma. All nodules were surgically resected and histopathologically confirmed as malignant insulinomas. Findings from the current study indicated that contrast-enhanced ultrasound may help to increase conspicuity of pancreatic insulinomas in dogs and that enhancement characteristics may be more variable in dogs than in humans. (C) 2014 American College of Veterinary Radiology.
  • Yu Tamura, Hiroshi Ohta, Nozomu Yokoyama, Sue Yee Lim, Tatsuyuki Osuga, Keitaro Morishita, Kensuke Nakamura, Masahiro Yamasaki, Mitsuyoshi Takiguchi
    JOURNAL OF VETERINARY MEDICAL SCIENCE 76 10 1407 - 1410 2014年10月 [査読有り][通常論文]
     
    Lymphocytic-plasmacytic colitis (LPC) is a common form of inflammatory bowel disease (IBD) affecting the canine large intestine. Cytokines are thought to be involved in the pathogenesis of IBD. However, to date, few studies have investigated cytokine mRNA expression in dogs with LPC. In this study, we investigated mRNA transcription levels of T helper cell cytokines, such as IFN-gamma, IL-4, IL-17 and IL-10 and pro-inflammatory cytokines, such as IL-1 beta, IL-6, TNF-alpha., IL-8, IL-12 and IL-23, in colonic mucosa from LPC dogs by quantitative real-time RT-PCR. No significant differences were detected in cytokine mRNA expressions between dogs with LPC and controls, except for IL-23p19. Dogs with LPC failed to express a predominant cytokine profile in inflamed colonic mucosa as opposed to human IBD.
  • Masahiro Yamasaki, Eriko Harada, Yu Tamura, Sue Yee Lim, Tatsuyuki Ohsuga, Nozomu Yokoyama, Keitaro Morishita, Kensuke Nakamura, Hiroshi Ohta, Mitsuyoshi Takiguchi
    VETERINARY PARASITOLOGY 205 3-4 424 - 433 2014年10月 [査読有り][通常論文]
     
    Babesia gibsoni is a causative pathogen of canine babesiosis, which is commonly treated with anti-babesial drugs; however, the development of novel, more effective anti-babesial drugs is necessary because the currently used drugs cannot remove the parasites from dogs. Therefore we investigated the anti-babesial effect of amphotericin B (AmB), a membrane-active polyene macrolide antibiotic. The interaction of such compounds with sterols in bilayer cell membranes can lead to cell damage and ultimately cell lysis. AmB exhibits in vitro activity against B. gibsoni in normal canine erythrocytes within 12 h. We also studied liposomal AmB (L-AmB), a liposomal formulation of AmB that required a longer incubation period to reduce the number of parasites. However, L-AmB completely inhibited the invasion of free parasites into erythrocytes. These results indicated that free parasites failed to invade erythrocytes in the presence of L-AmB. Both AmB and L-AmB induced mild hemolysis of erythrocytes. Moreover, the methemoglobin level and the turbidity index of erythrocytes were significantly increased when erythrocytes were incubated with AmB, suggesting that AmB induced oxidative damage in erythrocytes. Finally, the anti-babesial activity of AmB in vivo was observed. When experimentally B. gibsoni-infected dogs were administered 0.5 and 1 mg/kg AmB by the intravenous route, the number of parasites decreased; however, recurrence of parasitemia was observed, indicating that AmB did not eliminate parasites completely. Blood urea nitrogen and creatinine of dogs were abnormally elevated after the administration of 1 mg/kg AmB. These results indicate that AmB has in vivo activity against B. gibsoni; however, it does not eliminate parasites from infected dogs and affects kidney function at a high dose. (C) 2014 Elsevier B.V. All rights reserved.
  • Yu Tamura, Hiroshi Ohta, Takuya Kashiide, Jun Matsumoto, Tatsuya Sakurai, Nozomu Yokoyama, Keitaro Morishita, Kensuke Nakamura, Masahiro Yamasaki, Mitsuyoshi Takiguchi
    VETERINARY PARASITOLOGY 205 1-2 412 - 415 2014年09月 [査読有り][通常論文]
     
    An eight-year-old, neutered, female Shetland Sheepdog presented with a 6-week history of small intestinal diarrhea. Regenerative anemia, hypoproteinemia, and an increased plasma C-reactive protein concentration were detected On blood examination. Fecal examination and abdominal radiography were unremarkable. Abdominal ultrasonography showed diffusely hyperechoic mucosa in the small intestine. Gastroduodenoscopy, performed under general anesthesia, revealed mucosal edema and increased granularity in the duodenum and jejunum. Histopathological examination of the endoscopically biopsied small intestinal mucosa revealed tapeworm infection. A single administration of a combined anthelmintic drug (5 mg/kg praziquantel, 14.4 mg/kg pyrantel pamoate, and 15 mg/kg febantel) was successful for deworming, and the dog fully recovered. The parasites were removed from stored frozen duodenal mucosa and morphologically identified as Mesocestoides sp. immature adult worms. Mitochondrial (mt) 12S rDNA and mt cytochrome c oxide subunit I genes were amplified from the parasites. DNA sequence analysis showed that the genes shared 100% identity with those of reported M. vogae (syn. M. corti). This is the first reported case of protein-losing enteropathy caused by M. vogae in a dog. (C) 2014 Elsevier B.V. All rights reserved.
  • Hiroshi Ohta, Yuji Sunden, Nozomu Yokoyama, Tatsuyuki Osuga, Sue Yee Lim, Yu Tamura, Keitaro Morishita, Kensuke Nakamura, Masahiro Yamasaki, Mitsuyoshi Takiguchi
    AMERICAN JOURNAL OF VETERINARY RESEARCH 75 8 746 - 751 2014年08月 [査読有り][通常論文]
     
    Objective-To determine the expression of tight junction and adherens junction proteins in duodenal mucosa samples of dogs with inflammatory bowel disease (IBD). Animals-12 dogs with IBD and 6 healthy control Beagles. Procedures-Duodenal mucosa biopsy samples were endoscopically obtained from dogs with IBD and healthy control Beagles. The expression of claudin-1, -2, -3, -4, -5, -7, and -8; E-cadherin; and beta-catenin in the duodenal mucosa samples was determined by means of immunoblotting. The subcellular localization of E-cadherin in the duodenal mucosa samples was determined with immunofluorescence microscopy. Results-The expression of each claudin and beta-catenin was not significantly different between control dogs and dogs with IBD. However, expression of E-cadherin was significantly lower in duodenal mucosa samples of dogs with IBD than it was in samples obtained from healthy control dogs. Results of immunofluorescence microscopy indicated decreased intensity of E-cadherin labeling in the tips of villi in duodenal mucosa samples obtained from 6 dogs with IBD, compared with staining intensity for other dogs. Conclusions and Clinical Relevance-Results of this study indicated expression of claudin-1, -2, -3, -4, -5, -7, and -8 and beta-catenin was not significantly different between duodenal mucosa samples obtained from control dogs and those obtained from dogs with IBD. However, E-cadherin expression was significantly lower in the villus epithelium in duodenal mucosa samples obtained from dogs with IBD versus samples obtained from control dogs, which suggested that decreased expression of that protein has a role in the pathogenesis of IBD in dogs.
  • S. Y. Lim, K. Nakamura, K. Morishita, N. Sasaki, M. Murakami, T. Osuga, H. Ohta, M. Yamasaki, M. Takiguchi
    JOURNAL OF VETERINARY INTERNAL MEDICINE 28 2 496 - 503 2014年03月 [査読有り][通常論文]
     
    Background Acute pancreatitis (AP) is the most common disease of the canine exocrine pancreas, and accurate noninvasive diagnosis is challenging. Hypothesis/Objectives To determine the feasibility of using quantitative contrast-enhanced ultrasonography (CEUS) to detect pancreatic perfusional changes in cerulein-induced AP in dogs. Animals Six adult female Beagles. Methods Each dog received 2hours of IV infusion with 7.5 mu g/kg/h of cerulein diluted in saline. As control, all dogs received 2hours of IV infusion of saline 2weeks before cerulein infusion. CEUS of the pancreas and duodenum were performed before (0hour), and at 2, 4, 6, and 12hours after saline and cerulein infusion. Time-intensity curves were created from regions of interest in the pancreas and duodenum. Five perfusional parameters were measured for statistical analysis: time to initial up-slope, peak time, time to wash-out, peak intensity (PI), and area under the curve (AUC). Results In cerulein-induced AP, pancreatic PI increased at 2 and 4hours when compared to 0hour, and at 2, 4, and 6hours when compared to control. AUC increased at 4hours when compared to 0hour, and at 2 and 4hours when compared to control. Time to wash-out was prolonged at 4hours when compared to control. For saline control, peak time was faster at 2hours when compared to 0hour. Conclusions and Clinical Importance CEUS parameters PI and AUC can provide useful information in differentiating acute pancreatitis from normal pancreas. Cerulein-induced AP was characterized by prolonged hyperechoic enhancement on CEUS.
  • Nakamura K, Osuga T, Morishita K, Suzuki S, Morita T, Yokoyama N, Ohta H, Yamasaki M, Takiguchi M
    Journal of Veterinary Internal Medicine 28 6 1746 - 1752 Wiley-Blackwell 2014年 [査読有り][通常論文]
     
    Background: A strong correlation between left atrial (LA) dysfunction and the severity of cardiac disease has been described in human patients with various cardiac diseases. The role of LA dysfunction in dogs with chronic mitral valvular heart disease (CMVHD) has not been addressed. Objectives: To investigate the correlation between LA function and the prognosis of dogs with CMVHD. Animals: Thirty-eight client-owned dogs with CMVHD. Methods: Prospective clinical cohort study. Dogs were divided into 2 groups (survivors and nonsurvivors) based on the onset of cardiac-related death within 1year. Physical examination and echocardiographic variables were compared between the groups. For the assessment of the comparative accuracy in identifying patients with cardiac-related death, receiver operating characteristic (ROC) curves and multivariate logistic analysis were used. Results: The highest accuracy was obtained for the LA active fractional area change (LA-FAC(act)), with an area under the ROC curve (AUC) of 0.95, followed by the left atrial to aortic root ratio (LA/Ao), with an AUC of 0.94; peak early diastolic mitral inflow velocity (E), with an AUC of 0.85; and LA total fractional area change (LA-FAC(total)), with an AUC of 0.85. In the multivariate logistic regression analysis, LA-FAC(act) emerged as the only independent correlate of cardiac-related death within 1year (odds ratio=1.401, P=.002). Conclusions and Clinical Importance: Regarding both the size and function, the LA has a strong correlation with the prognosis of dogs with CMVHD. The most significant independent predictor of mortality in this study was LA-FAC(act).
  • Sue Yee Lim, Kensuke Nakamura, Keitaro Morishita, Noboru Sasaki, Masahiro Murakami, Tatsuyuki Osuga, Hiroshi Ohta, Masahiro Yamasaki, Mitsuyoshi Takiguchi
    JOURNAL OF VETERINARY MEDICAL SCIENCE 75 12 1601 - 1607 2013年12月 [査読有り][通常論文]
     
    Quantitative contrast enhanced ultrasound is a major breakthrough for ultrasound imaging in recent years. However, contrast enhancement of the pancreas is brief with bolus injection. To assess if continuous infusion of Sonazoid (R) can prolong the duration of pancreatic enhancement over bolus injections, eight adult dogs received bolus injection and continuous infusion of Sonazoid (R) on separate days. Contrast enhanced ultrasound of the pancreatic parenchyma and proximal descending duodenum was performed, and time intensity curves reflecting tissue perfusions were generated. Perfusion parameters- time to initial upslope, peak time, time to wash-out and peak intensity were calculated and evaluated. Fast wash-in to intense peak, followed by rapid wash-out was observed for time intensity curves of bolus injection. With continuous infusion, contrast wash-in to peak intensity was gradual, followed by long plateau and slow wash-out. Median contrast enhancement durations of the pancreas and duodenum were significantly prolonged by continuous infusion from 11 sec (range, 10 to 23 sec) and 16 sec (range, 3 to 43 sec) at bolus injection to 205 sec (range, 170 to 264 sec, P<0.01) and 193 sec (range, 169 to 216 sec, P<0.05), respectively. Median peak intensity of the pancreas was 100.9 MPV (range, 80.2 to 124.3 MPV) at bolus injection and 77.6 MPV (range, 58.2 to 99.5 MPV, P<0.05) at continuous infusion. Prolonged continuous imaging is afforded by continuous infusion of contrast agent. Peak intensity of the pancreas was slightly diminished in continuous infusion, but offered adequate imaging subjectively.
  • 組織奇形が疑われた膀胱粘膜下嚢胞の犬の1例
    森下 啓太郎, 細谷 謙次, 大菅 辰幸, 中村 健介, 大田 寛, 山崎 真大, 滝口 満喜
    動物臨床医学会年次大会プロシーディング 34回 2 9 - 10 動物臨床医学会 2013年11月
  • Yu Tamura, Hiroshi Ohta, Shidow Torisu, Masashi Yuki, Nozomu Yokoyama, Masahiro Murakami, Sue Yee Lim, Tatsuyuki Osuga, Keitaro Morishita, Kensuke Nakamura, Masahiro Yamasaki, Mitsuyoshi Takiguchi
    VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY 156 1-2 32 - 42 2013年11月 [査読有り][通常論文]
     
    Inflammatory colorectal polyps (ICRPs) in miniature dachshunds were recently recognized as a major cause of large bowel diarrhea in this dog breed in Japan. ICRPs are characterized by the formation of multiple small polyps and/or space-occupying large polyps in the colorectal area and are thought to be a novel form of inflammatory bowel disease (IBD). To explore key mediators in the pathogenesis of ICRPs, we analyzed several pro-inflammatory cytokine (IL-1 beta, IL-6, TNF-alpha, IL-8, IL-12p35, IL-12/23p40, and IL-23p19) mRNA expressions in colorectal polyps in ICRP dogs by quantitative PCR. Among these cytokines, IL-8 mRNA expression was markedly up-regulated in large polyps. To examine IL-8 protein expression, we analyzed IL-8 protein level and its location in colorectal mucosal specimens of ICRP dogs by ELISA and immunofluorescence microscopy. IL-8 protein was significantly increased in large polyps and serum in dogs with ICRPs compared to controls. By immunofluorescence microscopy, IL-8 was only localized in macrophages, but not in mucosal epithelial cells or neutrophils. IL-8-positive macrophages were significantly increased in large polyps compared to controls. These results suggest that IL-8 is produced mainly by macrophages and may induce neutrophil infiltration in the colorectal area of ICRP dogs. (C) 2013 Elsevier B.V. All rights reserved.
  • 2D Speckle Tracking法を用いた左心房機能評価による犬心筋症の重症度評価
    大菅 辰幸, 中村 健介, 細谷 謙次, 森下 啓太郎, 大田 寛, 山崎 真大, 滝口 満喜
    北海道獣医師会雑誌 57 8 396 - 396 (公社)北海道獣医師会 2013年08月
  • 閉鎖式持続吸引ドレーンにて良好にコントロールできた膵膿瘍の犬の1例
    山口 朋生, 森下 啓太郎, 細谷 謙次, 向谷 竜介, 中村 健介, 大田 寛, 山崎 真大, 滝口 満喜
    北海道獣医師会雑誌 57 8 400 - 400 (公社)北海道獣医師会 2013年08月
  • 特発性収縮性心膜炎の犬の1例
    大菅 辰幸, 中村 健介, 細谷 謙次, 森田 智也, 賀川 由美子, 森下 啓太郎, 大田 寛, 山崎 真大, 滝口 満喜
    獣医麻酔外科学雑誌 44 Suppl.1 245 - 245 (一社)日本獣医麻酔外科学会 2013年06月
  • Tatsuyuki Osuga, Kensuke Nakamura, Sue Yee Lim, Yu Tamura, Wickramasekara Rajapakshage Bandula Kumara, Masahiro Murakami, Noboru Sasaki, Keitaro Morishita, Hiroshi Ohta, Masahiro Yamasaki, Mitsuyoshi Takiguchi
    AMERICAN JOURNAL OF VETERINARY RESEARCH 74 6 864 - 869 2013年06月 [査読有り][通常論文]
     
    Objective-To evaluate left atrial phasic function in healthy dogs by means of 2-D speckle tracking echocardiography with time-left atrial area curve analysis and to assess repeatability and reproducibility of obtained measurements. Animals-6 healthy Beagles. Procedures-Each dog underwent echocardiography twice on different days (3 nonconsecutive examinations/d). Images were analyzed with offline software; area of the left atrium was automatically calculated in each frame throughout the cardiac cycle to derive time-left atrial area curves. Variables used to assess left atrial phasic function (total, passive, and active emptying area and emptying fractions and mean active and total emptying rates) were calculated. Agreement between variables measured via speckle tracking echocardiography and a manual tracing method was assessed with modified Bland-Altman analysis. Withinday and between-day coefficients of variation were determined. Results-Mean +/- SD total, passive, and active emptying fractions of the left atrium were 49.8 +/- 3.5%, 27.7 +/- 4.0%, and 30.5 +/- 4.3%, respectively. Mean +/- SD total and active emptying rates were 16.0 +/- 2.5 cm(2)/s and 25.1 +/- 4.9 cm(2)/s, respectively. Within-day and between-day coefficients of variation were < 20% (range, 0.41% to 16.4%) for all variables except mean active emptying rate (between-day coefficient of variation, 29.2%). Agreement between variables measured via speckle tracking echocardiography and the manual tracing method was good, and differences between methods were nonsignificant. Conclusions and Clinical Relevance-Evaluation of left atrial phasic function via speckle tracking echocardiography was feasible; repeatability and reproducibility of measurements were adequate in healthy dogs. Studies are needed to determine clinical applicability in canine patients. (Am J Vet Res 2013;74:864-869)

書籍

  • 森下啓太郎 (担当:分担執筆範囲:鉄欠乏性貧血、腎性貧血、慢性疾患に伴う貧血)
    緑書房 2021年03月 (ISBN: 9784895315852) 503p
  • 森下啓太郎 (担当:分担執筆範囲:門脈圧亢進症、)
    Eduward press 2020年08月 (ISBN: 9784866711225) xvi, 963, 23p
  • 森下啓太郎 (担当:分担執筆範囲:門脈圧亢進症、免疫介在性好中球減少症、非再生性免疫介在性貧血、血球貪食性組織球性肉腫)
    Eduward press 2020年08月 (ISBN: 9784866711218) xvi, 1219, 28p
  • 森下啓太郎 (担当:分担執筆範囲:鉄欠乏性貧血、腎性貧血、慢性疾患に伴う貧血)
    緑書房 2017年08月 (ISBN: 9784895313100) 冊

講演・口頭発表等

  • 初期診断が困難であった血球貪食性組織球性肉腫の犬の1例
    森下啓太郎
    日本獣医臨床病理学会2021年次大会 口頭発表(一般)
  • 骨髄の評価  [招待講演]
    森下啓太郎
    第17回日本獣医内科学アカデミー学術大会 2021年02月 口頭発表(招待・特別)
  • 免疫介在性溶血性貧血の診断と治療 米国獣医内科学会consensus statement準拠  [招待講演]
    森下 啓太郎
    動物臨床医学会年次大会プロシーディング 2020年11月 動物臨床医学会
  • ACVIMコンセンサスガイドラインからおさえるIMHA治療編  [招待講演]
    森下啓太郎
    第16回日本獣医内科学アカデミー学術大会 2020年02月 口頭発表(招待・特別)
  • 顕微鏡DEディスカッション  [招待講演]
    森下啓太郎
    第39回動物臨床医学会年次大会 2019年11月 シンポジウム・ワークショップパネル(指名)
  • 免疫介在性溶血性貧血(IMHA)の診断  [招待講演]
    森下啓太郎
    第15回日本獣医内科学アカデミー学術大会 2019年02月 口頭発表(招待・特別)
  • 非再生性貧血の診断と治療  [招待講演]
    森下啓太郎
    第15回日本獣医内科学アカデミー学術大会 2019年02月 口頭発表(招待・特別)
  • 尿中メタネフリン分画測定が診断の決め手となった副腎偶発腫の犬の2例
    立花由莉加, 森下啓太郎, 高木哲, 大田寛, 佐々木東, 大菅辰幸, 滝口満喜
    第14回日本獣医内科学アカデミー学術大会 2018年02月
  • 血液疾患と間違えやすい病態を理解する  [招待講演]
    森下啓太郎
    第14回日本獣医内科学アカデミー学術大会 2018年02月 口頭発表(招待・特別)
  • up-date ヘプシジンの発見で変わった 腎性貧血のメカニズム  [招待講演]
    森下啓太郎
    第14回日本獣医内科学アカデミー学術大会 2018年02月 口頭発表(招待・特別)
  • 犬の非再生性免疫介在性貧血の臨床病理所見と治療反応に関する回顧的研究
    岩永優斗, 森下啓太郎, 細谷謙次, 大菅辰幸, 佐々木東, 大田寛, 滝口満喜
    北海道獣医師会雑誌 2018年
  • 感染性動脈瘤の猫の1例
    森下啓太郎, 高木哲, 賀川由美子, 華園究, 佐々木東, 大田寛, 滝口満喜
    第9回北海道・九州小動物獣医療ジョイントシンポジウム 2017年12月
  • 猫のCKDの治療最前線 腎性貧血の病態と治療  [招待講演]
    森下 啓太郎
    動物臨床医学会年次大会プロシーディング 2017年11月 シンポジウム・ワークショップパネル(指名) 動物臨床医学会
  • 森下啓太郎, 中島彩乃, 賀川由美子, 華園究, 佐々木東, 大田寛, 滝口満喜
    日本獣医画像診断学会抄録(Web) 2017年09月 (一社)日本獣医画像診断学会
  • 高村 大地, 森下 啓太郎, 中島 彩乃, 竹内 恭介, 佐々木 東, 大田 寛, 滝口 満喜
    北海道獣医師会雑誌 2017年08月 (公社)北海道獣医師会
  • 道下 明日香, 森下 啓太郎, 橋場 香野, 田村 昌大, 金 尚昊, 佐々木 東, 大田 寛, 滝口 満喜
    北海道獣医師会雑誌 2017年08月 (公社)北海道獣医師会
  • 田村 昌大, 森下 啓太郎, 高木 哲, 早川 小百合, 賀川 由美子, 佐々木 東, 大田 寛, 滝口 満喜
    北海道獣医師会雑誌 2017年08月 (公社)北海道獣医師会
  • Remarked megakaryocytic dysplasia in a dog with non-regenerative anemia
    森下啓太郎
    日本獣医臨床病理学会2017年大会 2017年06月 口頭発表(一般)
  • 犬の原発性免疫介在性血小板減少症(pIMT)の回顧的研究
    高村大地, 森下啓太郎, 中島彩乃, 竹内恭介, 大菅辰幸, 佐々木東, 大田寛, 滝口満喜
    第14回日本獣医内科学アカデミー学術大会 2017年02月
  • 造影超音波検査による門脈高血圧の新しい診断法  [招待講演]
    森下啓太郎
    第13回日本獣医内科学アカデミー学術大会 2017年02月 口頭発表(招待・特別)
  • 非再生性免疫介在性貧血(NRIMA)を徹底攻略 NRIMAの治療 脾摘は有効な手段か?  [招待講演]
    森下啓太郎
    第13回日本獣医内科学アカデミー学術大会 2017年02月 口頭発表(招待・特別)
  • 渡邉 清正, 森下 啓太郎, 中村 健介, 佐々木 東, 大田 寛, 滝口 満喜
    北海道獣医師会雑誌 2016年08月 (公社)北海道獣医師会
  • 肝膵疾患の超音波検査~基礎から応用まで~造影超音波検査の応用  [招待講演]
    第12回日本獣医内科学アカデミー学術大会 2016年02月 口頭発表(招待・特別)
  • クイズで学ぶ腹部画像診断  [招待講演]
    森下啓太郎
    第11回日本獣医内科学アカデミー学術大会 2015年02月 公開講演,セミナー,チュートリアル,講習,講義等
  • 臨床現場で必要な血液学入門  [招待講演]
    森下啓太郎
    北海道小動物獣医師会年次大会2014 2014年11月 公開講演,セミナー,チュートリアル,講習,講義等
  • 肝静脈血流指標による門脈圧亢進症の非侵襲的評価の試み  [招待講演]
    森下啓太郎
    第56回日本獣医画像診断学会 2014年09月 公開講演,セミナー,チュートリアル,講習,講義等
  • 貧血の鑑別診断  [招待講演]
    森下啓太郎
    北海道九州小動物獣医療ジョイントシンポジウム2013 2013年12月 公開講演,セミナー,チュートリアル,講習,講義等

その他活動・業績

受賞

  • 2020年02月 臨床研究アワード(インターズー学術奨励賞)非再生性貧血のミニチュア・ダックスフンド11例に対する脾臓摘出術の治療成績 第16回日本獣医内科学アカデミー学術大会(JCVIM2020))
     
    受賞者: 菅原芽伊;森下啓太郎, 今井 健友, 山崎 淳平, 佐々木 東, 大田 寛, 細谷 謙次, 滝口 満喜
  • 2019年08月 令和元年度 北海道地区学会北海道獣医師会長賞
     
    受賞者: 細田 千尋, 森下 啓太郎, 山崎 淳平, 高田 健介, 細谷 謙次, 金 尚昊, 佐々木 東, 大田 寛, 滝口 満喜
  • 2018年08月 平成30年度 北海道地区学会奨励賞
     
    受賞者: 岩永 優斗, 森下 啓太郎, 細谷 謙次, 大菅 辰幸, 佐々木 東, 大田 寛, 滝口 満喜
  • 2014年09月 平成26年度 日本小動物獣医学会地区学会長賞
     
    受賞者: 森下啓太郎

共同研究・競争的資金等の研究課題

  • ミニチュア・ダックスフンドに好発する非再生性貧血の病態解明
    日本学術振興会:科学研究費助成事業 若手研究
    研究期間 : 2019年04月 -2022年03月 
    代表者 : 森下 啓太郎
     
    本邦のミニチュア・ダックスフンドには、原因不明の非再生性貧血が好発する。本研究では脾臓摘出によって造血能が劇的に回復するという知見を基に、貧血の原因をTGF-βシグナル異常に起因する造血障害としてとらえ、脾臓におけるTGF-βの過剰産生の有無、および骨髄におけるTGF-β制御因子の異常発現の有無を明らかにすることを目的とした。 非再生貧血を呈するミニチュア・ダックス11頭で脾臓摘出術を実施した。年齢の中央値は12歳(範囲:5-15歳)、体重の中央値は5.12 kg(範囲:3.4-7.66 kg)であり、性別は雄4頭(全て去勢済)、雌7頭(避妊済み3頭)であった。術前の免疫抑制療法の実施日数は中央値112日(範囲:52-237日)、輸血間隔の中央値は34日(範囲:4-207 日)であった。脾摘による治療反応を評価したところ、7頭が有効、2頭が無効、2頭が治療判定不可に分類された。摘出された脾臓の病理組織診断は全例で髄外造血であり、罹患犬の脾臓には対照群(ミニチュアダックス以外の髄外造血サンプル)に比べ淡明核を有する巨核球の有意な増加を認めた。治療効果を判定可能であった9頭に対し脾臓におけるTGF-β関連分子のmRNA発現量をリアルタイムPCR法で定量したところ、脾摘有効群は無効群に比べTGF-β発現が高い傾向を得た。TGF-β受容体, SMAD-2, SMAD-3, SMAD7に関しては一定の傾向は認められなかった。
  • 視点移動可能な映像教材を用いた臨場感のある獣医臨床教育手技教育教材の開発
    日本学術振興会:科学研究費助成事業 挑戦的研究(萌芽)
    研究期間 : 2018年06月 -2021年03月 
    代表者 : 高木 哲, 藤田 良治, 森下 啓太郎
     
    今年度はまず映像をいくつかの取り組みごとに分類してそれぞれのアプローチから視点移動教材作成の可能性についての検証を始めた。これらは ①VR映像 ②ハイビジョン内視鏡映像 ③8K映像 ④2D/3Dアニメーション に分類した。、 ①VR教材については市販の360度カメラを用いて気管挿管の処置を撮影した。この際、複数の人物の動きが同時に進行することにより、それぞれの担当がいつどのような動きをしているか、視点を移動することで確認することができるようになった。 ②ハイビジョン内視鏡映像については特に口腔や膣内などの通常映像では観察しがたい映像も得ることができた。しかし、教育的にはこれまでの教材と比較すると劇的に貢献度が大きかったものの、任意の視点移動はもちろんできず、厳格に判断すれば内視鏡で得られる一般的な画像以上の情報はなかった。今後非生体モデル等を併用した場合に学生が自分で操作することで教育効果が高められる可能性は示唆された。③8K映像については当初非常に繊細で画角が大きいために大きく拡大するすることができるということで去勢手術を撮影してみたが、カメラ自体は定点であるのでそこからの視野は移動できないことは弱点であったが、何より8K映像を再生できるデバイスが広く普及していないため、この教材は現時点では汎用には向かないと判断した。ただし、今回撮影されたのは獣医学領域の手術として世界で初めての8K映像で撮影されたものとなる。④3Dアニメーションは全ての物体の空間上の点の位置を完全に正確に規定する必要があるため作成には非常に時間がかかるが、これに対して架空のカメラを全方位から動かすことができるため、とくに皮膚の下や口の中などの手技については非常に有用性の高い教材と判断された。しかし、任意の視点移動には簡単に操作をできるソフトが必要だと考えらえた。
  • 日本学術振興会:科学研究費助成事業 研究活動スタート支援
    研究期間 : 2012年08月 -2014年03月 
    代表者 : 森下 啓太郎
     
    慢性腎疾患(CKD)はイヌやネコで多く認められる。しかし現在の腎機能検査は、病気が進行して初めて異常値を示すため、より早期に腎臓へのダメージを知る検査が必要である。本研究では、造影超音波検査(CEUS)による腎血流量の評価がイヌのCKD診断に応用できるか検討した。 最初に健常犬6頭を用いてCEUSの方法を確立し、正常値を求めた。次にCKDの犬15頭に対しCEUSを実施した。CKDでは、腎機能障害が重度になるとCEUSによる造影増強効果の減弱が認められた。しかし腎障害が軽度の場合、健常犬のCEUS所見と比べ明かな変化は観察されなかった。今後は本検査が腎疾患の進行予測に利用できないか検討したい。

教育活動情報

主要な担当授業

  • 総合専門臨床特論
    開講年度 : 2021年
    課程区分 : 博士後期課程
    開講学部 : 獣医学院
  • 臨床画像診断学特論
    開講年度 : 2021年
    課程区分 : 博士後期課程
    開講学部 : 獣医学院
    キーワード : 画像診断学、放射線学、放射線腫瘍学、超音波検査、血液内科学、抗腫瘍療法、軟部組織外科学、神経外科学、神経内科学
  • 伴侶動物獣医療実習Ⅰ
    開講年度 : 2021年
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 伴侶動物、内科、外科、検査、診断、治療
  • 伴侶動物獣医療実習Ⅱ
    開講年度 : 2021年
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 伴侶動物、内科、外科、検査、診断、治療
  • 総合獣医療実習
    開講年度 : 2021年
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 臨床病理、画像診断、細胞診、病理解剖、麻酔
  • 夜間・救急獣医療実習Ⅰ
    開講年度 : 2021年
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 夜間・休日診療、救急処置
  • 獣医コミュニケーション演習
    開講年度 : 2021年
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 獣医療、調査研究、コミュニケーション、インフォームド・コンセント
  • 内科学各論
    開講年度 : 2021年
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 内科疾患、病態生理、臨床徴候、診断と治療
  • コミュニケーション論演習
    開講年度 : 2021年
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 獣医療、調査研究、コミュニケーション、インフォームド・コンセント
  • プレクリニカル実習
    開講年度 : 2021年
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 臨床診断学、獣医内科学、獣医外科学、繁殖学、画像診断学、伴侶動物、産業動物

大学運営

委員歴

  • 2020年04月 - 現在   日本獣医輸血研究会   認定委員会
  • 2018年11月 - 現在   動物臨床医学会   評議員


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