研究者情報

マスター

アカウント（マスター）

• 氏名

  滝口　満喜(タキグチ　ミツヨシ), タキグチ　ミツヨシ

所属（マスター）

• 獣医学研究院　獣医学部門　臨床獣医科学分野

所属（マスター）

• 獣医学研究院　獣医学部門　臨床獣医科学分野

独自項目

syllabus

• 2021, 臨床疾病学特論, Advanced Lecture on Veterinary Clinical Diseases, 博士後期課程, 獣医学院
• 2021, 獣医内科学特論, Advanced Lecture on Veterinary Internal Medicine, 博士後期課程, 獣医学院
• 2021, 総合専門臨床特論, Advanced and Comprehensive Studies on Integrated Specialized Veterinary Clinical Medicine, 博士後期課程, 獣医学院
• 2021, 伴侶動物獣医療実習Ⅰ, Practice in Companion Animal Medicine I, 学士課程, 獣医学部, 伴侶動物、内科、外科、検査、診断、治療
• 2021, 伴侶動物獣医療実習Ⅱ, Practice in Companion Animal Medicine II, 学士課程, 獣医学部, 伴侶動物、内科、外科、検査、診断、治療
• 2021, 総合獣医療実習, Practice in Comprehensive Veterinary Medicine, 学士課程, 獣医学部, 臨床病理、画像診断、細胞診、病理解剖、麻酔
• 2021, 夜間・救急獣医療実習Ⅰ, Practice in Night Times and Emergency Medicine I, 学士課程, 獣医学部, 夜間・休日診療、救急処置
• 2021, 獣医コミュニケーション演習, Seminar in Veterinary Communication, 学士課程, 獣医学部, 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
• 2021, 臨床動物栄養学, Clinical Animal Nutrition, 学士課程, 獣医学部, 栄養学、栄養管理
• 2021, 臨床動物行動学, Clinical Ethology, 学士課程, 獣医学部, 臨床行動学、問題行動、行動治療
• 2021, 内科学各論, Particular Internal Medicine, 学士課程, 獣医学部, 内科疾患、病態生理、臨床徴候、診断と治療
• 2021, 放射線獣医療・画像診断学, Radiation Veterinary Medicine and Diagnostic Imaging, 学士課程, 獣医学部, 画像診断　X線　超音波　CT　MRI　核医学　造影検査　放射線防護
• 2021, 放射線獣医療・画像診断学, Radiation Veterinary Medicine ･ Diagnostic Imaging, 学士課程, 獣医学部, 画像診断　X線　超音波　CT　MRI　核医学　造影検査　放射線防護
• 2021, コミュニケーション論演習, Seminar in Communication Theory, 学士課程, 獣医学部, 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
• 2021, プレクリニカル実習, Practice in Preclinical Medicine, 学士課程, 獣医学部, 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
• 2021, 内科学総論, General Internal Medicine, 学士課程, 獣医学部, 内科学、身体検査、診断、説明と同意

PositionHistory

• 教育研究評議会評議員, 2019年4月1日, 2021年3月31日
• 教育研究評議会評議員, 2021年4月1日, 2023年3月31日
• 獣医学部長, 2021年4月1日, 2023年3月31日
• 大学院獣医学研究院長, 2021年4月1日, 2023年3月31日
• 大学院獣医学研究院副研究院長, 2017年4月1日, 2019年3月31日
• 大学院獣医学研究院副研究院長, 2019年4月1日, 2021年3月31日
• 獣医学部長, 2023年4月1日, 2025年3月31日
• 大学院獣医学研究院長, 2023年4月1日, 2025年3月31日
• 大学院獣医学研究院附属動物病院長, 2016年4月1日, 2018年3月31日
• 大学院獣医学研究院附属動物病院長, 2018年4月1日, 2020年3月31日
• 大学院獣医学研究院附属動物病院長, 2020年4月1日, 2021年3月31日
• 大学院獣医学研究科附属動物病院長, 2014年4月1日, 2016年3月31日
• 大学院獣医学研究院附属動物病院長, 2023年4月1日, 2025年3月31日

researchmap

プロフィール情報

学位

• 博士（獣医学）（北海道大学）
• 修士（獣医学）（北海道大学）

プロフィール情報

• 姓

  滝口, 滝口

• 名

  満喜, 満喜

• ID各種

  200901022044782571

業績リスト

研究キーワード

• 慢性炎症   自己免疫疾患   超音波診断   画像診断   Veterinary Diagnostic imaging   Autoimmune Diseases   Diagnostic Ultrasound   Diagnostic imaging   

研究分野

• ライフサイエンス / 放射線科学
• ライフサイエンス / 膠原病、アレルギー内科学
• ライフサイエンス / 獣医学

経歴

• 2021年04月 北海道大学 大学院獣医学研究院 大学院獣医学研究院長・獣医学部長
• 2017年04月 北海道大学大学院獣医学研究院 教授
• 2007年10月 北海道大学 大学院獣医学研究科 教授
• 2004年10月 - 2007年09月 酪農学園大学 獣医学部 教授
• 2004年06月 北海道大学大学院獣医学研究科助教授
• 2000年 - 2004年 Lecturer, Graduate School of Veterinary Medicine,
• 2004年 - Professor, School of Veterinary Medicine, Rakuno gakuen Univ.
• 2004年 - Assistant Professor, Graduate School of Veterinary Medicine,
• 2000年07月 北海道大学大学院獣医学研究科講師
• 1995年 - 2000年 Instractor, Graduate School of Veterinary Medicine
• 1996年03月 - 1996年08月 文部省在外研究員
• 1995年04月 北海道大学大学院獣医学研究科助手
• 1993年 - 1995年 Instractor, Faculty of Veterinary Medicine, Hokkaido Univ.
• 1993年10月 北海道大学獣医学部助手
• 1992年06月 オハイオ州立大学獣医学部客員研究員
• 1989年04月 - 1992年05月 横浜動物医療センター
• Hokkaiddo Univ.

学歴

• 1987年04月 - 1989年03月   北海道大学   大学院獣医学研究科   （修士課程）予防治療学専攻
• 1983年04月 - 1987年03月   北海道大学   獣医学部   獣医学科

委員歴

• 2014年04月 - 現在   日本獣医学会   理事
• 2008年04月 - 2014年03月   日本獣医学会   評議委員
• 2003年   日本小動物獣医学会   理事   日本小動物獣医学会
• 2002年   日本獣医画像診断学会   理事   日本獣医画像診断学会

受賞

• 2004年 日本小動物獣医学会北海道獣医師会長賞
  
• 1999年 平成11年度日本小動物獣医学会(北海道)獣医師会長賞
  
• 1999年 日本獣医学会大会長賞 獣医学奨励賞
  
• 1998年 日本獣医学会大会長賞 獣医学奨励賞
  
• 1997年 平成9年度日本小動物獣医学会(北海道)地区学会長賞
  

論文

• Case report: Echinococcus multilocularis infection in a dog showing gastrointestinal signs in Hokkaido, Japan

  Izumi Kida, Naoki Hayashi, Nozomu Yokoyama, Noriyuki Nagata, Kazuyoshi Sasaoka, Noboru Sasaki, Keitaro Morishita, Kensuke Nakamura, Hirokazu Kouguchi, Kinpei Yagi, Ryo Nakao, Mitsuyoshi Takiguchi, Nariaki Nonaka

  Frontiers in Veterinary Science 11 2024年06月13日 [査読有り][通常論文]
   

  Echinococcus multilocularis is a cestode that causes human alveolar echinococcosis, a lethal zoonotic disease distributed in the northern hemisphere. The life cycle of this parasite is maintained in nature by voles as intermediate hosts and foxes as definitive hosts in Hokkaido, Japan. Although dogs are also susceptible to the parasite, the infection has been considered typically asymptomatic. We report the detection of E. multilocularis eggs in the diarrheal feces of a dog with chronic gastrointestinal signs, which disappeared after anthelmintic treatment. The mitochondrial genome sequence constructed by sequencing of the overlapping PCRs using DNA from the eggs was identical to the most predominant haplotype previously reported in red foxes in Hokkaido. This case highlights that Echinococcus infection should be considered as a differential diagnosis for diarrheal dogs in the disease endemic areas. Further efforts are needed to accumulate parasite genotypes in domestic dogs as well as humans to assess the risk of human infection from dogs.
• Urinary steroid profiling using liquid chromatography-tandem mass spectrometry for the diagnosis of canine Cushing's syndrome.

  N Nagata, H Sawamura, Y Ikenaka, K Morishita, K Hosoya, N Sasaki, K Nakamura, M Takiguchi

  Veterinary journal (London, England : 1997) 106151 - 106151 2024年05月29日 [査読有り][通常論文]
   

  Serum cortisol measurements by chemiluminescence enzyme immunoassay (CLEIA) are widely used to diagnose hypercortisolism (HC) or Cushing's syndrome in dogs. However, they are associated with problems such as the need for multiple blood collections under stressful conditions or cross-reactivity between hormones. Therefore, a less invasive and more accurate diagnostic method is required. This study aimed to develop a urinary steroid profile analysis method using liquid chromatography-tandem mass spectrometry (LC/MS/MS) and to evaluate its clinical usefulness. Sixty-five healthy dogs and 38 dogs with suspected HC were included in the study. Using LC/MS/MS, the levels of 11 steroid hormones in the urine were determined. We established the upper limit of the reference interval for each urinary steroid-to-creatinine ratio and evaluated their diagnostic performances. The levels of the five steroid hormones were significantly higher in the 14 dogs with HC than in the 24 dogs with mimicking HC and 65 healthy dogs. The urinary corticosterone-to-creatinine ratio showed the highest diagnostic accuracy (area under the curve, 0.96). A significant correlation was seen between urinary cortisol concentrations measured by LC/MS/MS and CLEIA (rs = 0.88, P <0.001), although the CLEIA measurements were significantly higher than the LC/MS/MS measurements (P <0.001). LC/MS/MS-based urinary steroid profiles are a promising tool for diagnosing canine HC.
• Antimicrobial resistance and self-reported hand hygiene awareness before and after an infection prevention and control programme: a 7-year analysis in a small animal veterinary teaching hospital

  K. Sasaoka, T. Sato, K. Morishita, K. Hosoya, N. Yokoyama, T. Sato, M. Horiuchi, M. Takiguchi

  The Veterinary Journal 106154 - 106154 2024年05月 [査読有り][通常論文]
  
• A de novo nonsense variant in the DMD gene associated with X-linked dystrophin-deficient muscular dystrophy in a cat.

  Nozomu Yokoyama, Yuki Matsumoto, Takahisa Yamaguchi, Kazuki Okada, Ryohei Kinoshita, Genya Shimbo, Hisashi Ukawa, Ryuga Ishii, Kensuke Nakamura, Jumpei Yamazaki, Mitsuyoshi Takiguchi

  Journal of veterinary internal medicine 2024年04月13日 [査読有り]
   

  BACKGROUND: X-linked dystrophin-deficient muscular dystrophy (MD) is a form of MD caused by variants in the DMD gene. It is a fatal disease characterized by progressive weakness and degeneration of skeletal muscles. HYPOTHESIS/OBJECTIVES: Identify deleterious genetic variants in DMD by whole-genome sequencing (WGS) using a next-generation sequencer. ANIMALS: One MD-affected cat, its parents, and 354 cats from a breeding colony. METHODS: We compared the WGS data of the affected cat with data available in the National Center for Biotechnology Information database and searched for candidate high-impact variants by in silico analyses. Next, we confirmed the candidate variants by Sanger sequencing using samples from the parents and cats from the breeding colony. We used 2 genome assemblies, the standard felCat9 (from an Abyssinian cat) and the novel AnAms1.0 (from an American Shorthair cat), to evaluate genome assembly differences. RESULTS: We found 2 novel high-impact variants: a 1-bp deletion in felCat9 and an identical nonsense variant in felCat9 and AnAms1.0. Whole genome and Sanger sequencing validation showed that the deletion in felCat9 was a false positive because of misassembly. Among the 357 cats, the nonsense variant was only found in the affected cat, which indicated it was a de novo variant. CONCLUSION AND CLINICAL IMPORTANCE: We identified a de novo variant in the affected cat and next-generation sequencing-based genotyping of the whole DMD gene was determined to be necessary for affected cats because the parents of the affected cat did not have the risk variant.
• Interventricular inflow time difference assessed by dual pulsed-wave Doppler echocardiography in dogs with myxomatous mitral valve disease

  T. Morita, K. Nakamura, T. Osuga, S. Kawamoto, M. Takiguchi

  Journal of Veterinary Cardiology 51 24 - 34 2024年02月 [査読有り][通常論文]
  
• Use of genome-wide DNA methylation analysis to identify prognostic CpG site markers associated with longer survival time in dogs with multicentric high-grade B-cell lymphoma.

  Yong Bin Teoh, Teita Ishizaki, Yumiko Kagawa, Shoko Yokoyama, Jaroslav Jelinek, Yuki Matsumoto, Hirotaka Tomiyasu, Hajime Tsujimoto, Mitsuyoshi Takiguchi, Jumpei Yamazaki

  Journal of veterinary internal medicine 38 1 316 - 325 2024年 [査読有り]
   

  BACKGROUND: DNA methylation analysis might identify prognostic CpG sites in CHOP-treated dogs with multicentric high-grade B-cell lymphoma (MHGL) with heterogenous prognosis. OBJECTIVE: To identify prognostic CpG sites of MHGL through genome-wide DNA methylation analysis with pyrosequencing validation. ANIMALS: Test group: 24 dogs. Validation group: 100 dogs. All client-owned dogs were diagnosed with MHGL and treated with CHOP chemotherapy. METHODS: Cohort study. DNA was extracted from lymph node samples obtained via FNA. Genome-wide DNA methylation analysis using Digital Restriction Enzyme Analysis of Methylation (DREAM) was performed on the test group to identify differentially methylated CpG sites (DMCs). Bisulfite pyrosequencing was used to measure methylation status of candidate DMCs in the validation group. Median survival times (MST) were analyzed using Kaplan-Meier (log-rank) product limit method. RESULTS: DREAM analyzed 101 576 CpG sites. Hierarchical clustering of 16 262 CpG sites in test group identified group with better prognosis (MST = 55-477 days vs 10-301 days, P = .007). Volcano plot identified 1371 differentially methylated CpG sites (DMCs). DMC near the genes of FAM213A (DMC-F) and PHLPP1 (DMC-P) were selected as candidates. Bisulfite-pyrosequencing performed on validation group showed group with methylation level of DMC-F < 40% had favorable prognosis (MST = 11-1072 days vs 8-1792 days, P = .01), whereas group with the methylation level combination of DMC-F < 40% plus DMC-P < 10% had excellent prognosis (MST = 18-1072 days vs 8-1792 days, P = .009). CONCLUSION AND CLINICAL IMPORTANCE: Methylation status of prognostic CpG sites delineate canine MGHL cases with longer MST, providing owners with information on expectations of potential improved treatment outcomes.
• Adrenocortical hypoperfusion detected by contrast-enhanced ultrasound in a dog with trilostane-induced hypoadrenocorticism.

  N Nagata, K Aoshima, K Nakamura, M Takiguchi

  The Journal of small animal practice 64 11 722 - 726 2023年11月 [査読有り]
   

  A 12-year-old neutered male Chihuahua dog was diagnosed with pituitary-dependent hypercortisolism and treated with trilostane. Eighty-nine days later, the dog showed lethargy accompanied by hyponatraemia and hyperkalaemia. Hypoadrenocorticism due to trilostane was suspected, but the result of the adrenocorticotropic hormone stimulation test was not conclusive. Contrast-enhanced ultrasound showed loss of adrenocortical blood flow in both adrenal glands, indicating adrenocortical hypoperfusion and isolated hypoadrenocorticism. Treatment with fludrocortisone acetate improved the condition and electrolyte abnormalities. Thirteen months later, the dog showed alopecia, and an adrenocorticotropic hormone stimulation test revealed increased cortisol concentration, indicating hypercortisolism recurrence. The dog died due to progressive deterioration 22 months after the initial presentation. Post-mortem examination revealed focally extensive necrosis with marked calcification in the parenchyma of the adrenal glands and regeneration of the cells in the zona fasciculata with severe fibrosis. Adrenocortical hypoperfusion detected by contrast-enhanced ultrasound can support the diagnosis of adrenal necrosis and hypoadrenocorticism.
• The role of heat shock protein 90 in the proliferation of Babesia gibsoni in vitro.

  Hiroka Tsutsumi, Moeko Abe, Naohiro Uchida, Mitsuyoshi Takiguchi, Masahiro Yamasaki

  Experimental parasitology 251 108567 - 108567 2023年08月 [査読有り]
   

  The present study investigated the role of heat shock protein 90 (HSP90) in the proliferation and survival of Babesia gibsoni in vitro. To detect the effect on the entry of B. gibsoni into host erythrocytes, the parasite was incubated with an antibody against B. gibsoni HSP90 (BgHSP90) for 24 h. The results of this experiment demonstrated that both the incorporation of [3H]hypoxanthine into the nucleic acids of B. gibsoni and the number of parasites were not altered, indicating that an anti-BgHSP90 antibody did not directly inhibit the entry of the parasite into erythrocytes. Moreover, two HSP90 inhibitors, geldanamycin (GA) and tanespimycin (17-AAG), were used to evaluate the function of BgHSP90. GA and 17-AAG decreased both the incorporation of [3H]hypoxanthine and the number of infected erythrocytes, suggesting that BgHSP90 plays important roles in DNA synthesis and the proliferation of B. gibsoni. The effect of 17-AAG on the parasites was weaker than that of GA. Additionally, the effect of GA on the survival and superoxide generation of canine neutrophils was assessed. The survival of canine neutrophils was not affected. The superoxide generation was strongly suppressed by GA. This result indicated that GA inhibited the function of canine neutrophils. Additional studies are necessary to elucidate the role of BgHSP90 in the proliferation of the parasite.
• Diverse genome-wide DNA methylation alterations in canine hepatocellular tumours.

  Yu Asari, Jumpei Yamazaki, Oo Thandar, Tamami Suzuki, Keisuke Aoshima, Kyosuke Takeuchi, Ryohei Kinoshita, Sangho Kim, Kenji Hosoya, Teita Ishizaki, Yumiko Kagawa, Jaroslav Jelinek, Shoko Yokoyama, Noboru Sasaki, Hiroshi Ohta, Kensuke Nakamura, Mitsuyoshi Takiguchi

  Veterinary medicine and science 2023年07月22日 [査読有り]
   

  BACKGROUND: Canine hepatocellular tumours (HCTs) are common primary liver tumours. However, the exact mechanisms of tumourigenesis remain unclear. Although some genetic mutations have been reported, DNA methylation alterations in canine HCT have not been well studied. OBJECTIVES: In this study, we aimed to analyse the DNA methylation status of canine HCT. METHODS: Tissues from 33 hepatocellular carcinomas, 3 hepatocellular adenomas, 1 nodular hyperplasia, 21 non-tumour livers from the patients and normal livers from 5 healthy dogs were used. We analysed the DNA methylation levels of 72,367 cytosine-guanine dinucleotides (CpG sites) in all 63 samples. RESULTS AND CONCLUSIONS: Although a large fraction of CpG sites that were highly methylated in the normal liver became hypomethylated in tumours from most patients, we also found some patients with less remarkable change or no change in DNA methylation. Hierarchical clustering analysis revealed that 32 of 37 tumour samples differed from normal livers, although the remaining 5 tumour livers fell into the same cluster as normal livers. In addition, the number of hypermethylated genes in tumour livers varied among tumour cases, suggesting various DNA methylation patterns in different tumour groups. However, patient and clinical parameters, such as age, were not associated with DNA methylation status. In conclusion, we found that HCTs undergo aberrant and diverse patterns of genome-wide DNA methylation compared with normal liver tissue, suggesting a complex epigenetic mechanism in canine HCT.
• An inflammatory bowel disease-associated SNP increases local thyroglobulin expression to develop inflammation in miniature dachshunds

  Yong Bin Teoh, Jing-Jing Jiang, Takeshi Yamasaki, Noriyuki Nagata, Toshiki Sugawara, Rie Hasebe, Hiroshi Ohta, Noboru Sasaki, Nozomu Yokoyama, Kensuke Nakamura, Yumiko Kagawa, Mitsuyoshi Takiguchi, Masaaki Murakami

  Frontiers in Veterinary Science 10 2023年07月14日 [査読有り]
   

  Inflammatory colorectal polyp (ICRP) in miniature dachshunds (MDs) is a chronic inflammatory bowel disease (IBD) characterized by granulomatous inflammation that consists of neutrophil infiltration and goblet cell hyperplasia in the colon. Recently, we identified five MD-associated single-nucleotide polymorphisms (SNPs), namely PLG, TCOF1, TG, COL9A2, and COL4A4, by whole-exome sequencing. Here, we investigated whether TG c.4567C&gt;T (p.R1523W) is associated with the ICRP pathology. We found that the frequency of the T/T SNP risk allele was significantly increased in MDs with ICRP. In vitro experiments showed that TG expression in non-immune cells was increased by inducing the IL-6 amplifier with IL-6 and TNF-α. On the other hand, a deficiency of TG suppressed the IL-6 amplifier. Moreover, recombinant TG treatment enhanced the activation of the IL-6 amplifier, suggesting that TG is both a positive regulator and a target of the IL-6 amplifier. We also found that TG expression together with two NF-κB targets, IL6 and CCL2, was increased in colon samples isolated from MDs with the T/T risk allele compared to those with the C/C non-risk allele, but serum TG was not increased. Cumulatively, these results suggest that the T/T SNP is an expression quantitative trait locus (eQTL) of TG mRNA in the colon, and local TG expression triggered by this SNP increases the risk of ICRP in MDs via the IL-6 amplifier. Therefore, TG c.4567C&gt;T is a diagnostic target for ICRP in MDs, and TG-mediated IL-6 amplifier activation in the colon is a possible therapeutic target for ICRP.
• Successful treatment of sclerosing encapsulating peritonitis in a cat using bioresorbable hyaluronate-carboxymethylcellulose membrane after surgical adhesiolysis and long-term prednisolone

  Nozomu Yokoyama, Ryohei Kinoshita, Hiroshi Ohta, Kazuki Okada, Genya Shimbo, Kazuyoshi Sasaoka, Noriyuki Nagata, Noboru Sasaki, Keitaro Morishita, Kensuke Nakamura, Yumiko Kagawa, Mitsuyoshi Takiguchi

  Journal of Feline Medicine and Surgery Open Reports 9 2 2023年07月 [査読有り]
   

  Case summary An 8-year-old neutered male domestic shorthair indoor cat was presented with an 8-week history of intermittent vomiting, anorexia and weight loss that had been unresponsive to supportive treatment. Abdominal ultrasound revealed plication of the small intestine and fluid accumulation proximal to the lesion, and a linear foreign body was suspected. An exploratory celiotomy showed cocoon-like encapsulation of the entire intestine. Surgical adhesiolysis and full-thickness biopsy were performed, and histopathologic examination revealed mild thickening of the visceral peritoneum with fibrin deposition, as well as mild neutrophil and lymphocyte infiltration. These findings were compatible with sclerosing encapsulating peritonitis (SEP). The cat recovered well postoperatively and was discharged the next day. Prednisolone was administered for 7 weeks to prevent recurrence of SEP. Five months after surgery, the cat was re-presented with anorexia and chronic vomiting. Based on the clinical examination findings, recurrent SEP was suspected. At the second surgery, surgical adhesiolysis was repeated and a bioresorbable hyaluronate-carboxymethylcellulose membrane was used to cover the serosal surface and thus prevent adhesion formation. Histopathologic findings of the peritoneal biopsy specimen confirmed SEP. Long-term prednisolone treatment (1 mg/kg for the first dose and 0.5 mg/kg every 48 h for maintenance) was administered postoperatively. The cat survived for more than 1239 days without recurrence. Relevance and novel information To our knowledge, this is the first report of SEP in a cat with long-term survival. The use of a bioresorbable hyaluronate-carboxymethylcellulose membrane and long-term prednisolone treatment may have prevented short-term and long-term recurrence, respectively, in this case.
• Investigation of the therapeutic effects, predictors, and complications of long-term immunosuppressive therapy in dogs with precursor-targeted immune-mediated anemia.

  Mei Sugawara-Suda, Keitaro Morishita, Yuto Iwanaga, Jumpei Yamazaki, Yumiko Kagawa, Nozomu Yokoyama, Noboru Sasaki, Hiroshi Ohta, Kensuke Nakamura, Mitsuyoshi Takiguchi

  The Journal of veterinary medical science 85 7 695 - 701 2023年07月01日 [査読有り]
   

  Dogs with precursor-targeted immune-mediated anemia (PIMA) are commonly treated with immunosuppressive therapy, but information on predictors of treatment response and response time is limited. Therefore, we retrospectively investigated predictive factors that influenced the treatment response and duration required to observe a response in dogs with PIMA receiving continuous immunosuppressive therapies for more than 105 days. Of 50 client-owned dogs that developed PIMA, 27 were included in this study, of which 18 were responders and 9 were non-responders to immunosuppressive therapies. Sixteen of the 18 responders responded to treatment within 60 days and the remaining 2 responded at 93 and 126 days, respectively. We found that an erythroid-maturation ratio of <0.17 may be a useful predictor for treatment response. In addition, complications of immunosuppressive therapies were investigated further in 50 dogs. Pancreatitis (n=4) and pneumonia (3) occurred over the entire treatment period, and infections such as abscesses (3) tended to be more common in dogs on an extended period of immunosuppressive therapy. These findings may be helpful when planning for the initial treatment and may provide evidence for informed consent about potential comorbidities throughout the treatment course.
• Effectiveness of 2‐dimensional shear wave elastography for noninvasive and reliable estimation of right atrial pressure in dogs with induced volume overload

  Masahiro Tamura, Hiroshi Ohta, Tatsuyuki Osuga, Mitsuyoshi Takiguchi

  Journal of Veterinary Internal Medicine 2023年04月10日 [査読有り]
  
• Evaluation of responses to immunosuppressive therapy in dogs with suspected non‐regenerative immune‐mediated anaemia: 11 cases (2012‐2018)

  K. Morishita, M. Sugawara‐Suda, J. Yamazaki, N. Sasaki, K. Nakamura, H. Ohta, M. Takiguchi

  Journal of Small Animal Practice 64 527  2023年04月07日 [査読有り]
  
• Zoobiquity experiments show the importance of the local MMP9-plasminogen axis in inflammatory bowel diseases in both dogs and patients.

  Takeshi Yamasaki, Noriyuki Nagata, Toru Atsumi, Rie Hasebe, Yuki Tanaka, Izuru Ohki, Shimpei Kubota, Yuta Shinohara, Yong Bin Teoh, Nozomu Yokoyama, Noboru Sasaki, Kensuke Nakamura, Hiroshi Ohta, Takehiko Katsurada, Yoshihiro Matsuno, Shintaro Hojyo, Shigeru Hashimoto, Mitsuyoshi Takiguchi, Masaaki Murakami

  International immunology 35 7 313 - 326 2023年03月18日 [査読有り]
   

  Using a zoobiquity concept, we directly connect animal phenotypes to a human disease mechanism: the reduction of local plasminogen levels caused by matrix metalloproteinase-9 (MMP9) activity is associated with the development of inflammation in the intestines of dogs and patients with inflammatory bowel disease. We first investigated inflammatory colorectal polyps (ICRPs), which are a canine gastrointestinal disease characterized by the presence of idiopathic chronic inflammation, in Miniature Dachshund (MD), and found 31 missense disease-associated SNPs by whole-exome sequencing. We sequenced them in 10 other dog breeds and found five, PLG, TCOF1, TG, COL9A2, and COL4A4, only in MD. We then investigated two rare and breed-specific missense SNPs (T/T SNPs), PLG: c.477G>T and c.478A>T, and found that ICRPs with the T/T SNP risk-alleles showed less intact plasminogen and plasmin activity in the lesions compared to ICRPs without the risk-alleles but no differences in serum. Moreover, we show that MMP9, which is a NF-κB target, caused the plasminogen reduction and that intestinal epithelial cells expressing plasminogen molecules were colocalized with epithelial cells expressing MMP9 in normal colons with the risk-alleles. Importantly, MMP9 expression in patients with ulcerous colitis or Crohn's disease also colocalized with epithelial cells showing enhanced NF-κB activation and less plasminogen expression. Overall, our zoobiquity experiments showed that MMP9 induces the plasminogen reduction in intestine, contributing to the development of local inflammation and suggesting the local MMP9-plasminogen axis is a therapeutic target in both dogs and patients. Therefore, zoobiquity-type experiments could bring new perspectives for biomarkers and therapeutic targets.
• Prognostic value of left atrial stiffness estimated using echocardiography in dogs with myxomatous mitral valve disease

  T. Osuga, K. Kuroda, T. Morita, N. Sasaki, K. Nakamura, M. Takiguchi

  Journal of Veterinary Cardiology 45 15 - 26 2023年02月 [査読有り]
   

  Introduction: No studies have investigated the prognostic value of left atrial stiffness (LASt) estimated using echocardiography in dogs with myxomatous mitral valve disease (MMVD). Animals: 72 dogs had MMVD and 46 dogs were healthy dogs. Materials and Methods: Clinical retrospective cohort study. The survival information of MMVD dogs that underwent echocardiographic examination was obtained. The peak velocities of early diastolic transmitral flow (E) and mitral annular motion as determined by pulsed wave Doppler (E′) were determined. The left atrial reservoir strain (εS) was determined by two-dimensional speckle tracking echocardiography of the left atrium. The LASt was estimated by the formula: E/E′/εS. The 95% prediction interval of LASt was computed from the data of the healthy dogs. Results: 17 dogs having MMVD died of cardiac-related causes with 55 MMVD dogs censored. The MMVD dogs with LASt > its 95% upper prediction limit (LASt > 0.56; n = 26; median survival time, 484 days; 95% confidence interval, 283 days-indeterminable) had shorter survival times (P<0.001) than those with LASt ≤ its 95% upper prediction limit (LASt ≤ 0.56; n = 46; median survival time, >1112 days; 95% confidence interval, indeterminable). Multivariable Cox's proportional hazard analysis demonstrated that the ratio of the left atrial dimension to the aortic annulus dimension and LASt were independent predictors of cardiac-related death among conventional echocardiographic indices, εS and LASt in MMVD dogs. Conclusions: In dogs with MMVD, increased LASt estimated using echocardiography is an independent predictor of cardiac-related death, and LASt can be more useful for prognostication than εS.
• Transcriptome and proteome analysis of dogs with precursor targeted immune-mediated anemia treated with splenectomy.

  Mei Sugawara-Suda, Keitaro Morishita, Osamu Ichii, Takashi Namba, Keisuke Aoshima, Yumiko Kagawa, Sangho Kim, Kenji Hosoya, Nozomu Yokoyama, Noboru Sasaki, Kensuke Nakamura, Jumpei Yamazaki, Mitsuyoshi Takiguchi

  PloS one 18 5 e0285415  2023年 [査読有り]
   

  Precursor-targeted immune-mediated anemia (PIMA) in dogs is characterized by persistent non-regenerative anemia and ineffective erythropoiesis, and it is suspected to be an immune-mediated disease. Most affected dogs respond to immunosuppressive therapies; however, some are resistant. In this study, we carried out splenectomy as an alternative therapy for refractory PIMA in dogs, and analyzed gene expression levels in the spleen of dogs with or without PIMA and in serum before and after splenectomy. A total of 1,385 genes were found to express differentially in the spleens from dogs with PIMA compared with healthy dogs by transcriptome analysis, of which 707 genes were up-regulated, including S100A12, S100A8, and S100A9 that are linked directly to the innate immune system and have been characterized as endogenous damage-associated molecular patterns. Furthermore, immunohistochemistry confirmed that S100A8/A9 protein expression levels were significantly higher in dogs with PIMA compared with those in healthy dogs. A total of 22 proteins were found to express differentially between the serum samples collected before and after splenectomy by proteome analysis, of which 12 proteins were up-regulated in the samples before. The lectin pathway of complement activation was identified by pathway analysis in pre-splenectomy samples. We speculated that S100A8/9 expression may be increased in the spleen of dogs with PIMA, resulting in activation of the lectin pathway before splenectomy. These findings further our understanding of the pathology and mechanisms of splenectomy for PIMA.
• Biological effects related to exposure to polychlorinated biphenyl (PCB) and decabromodiphenyl ether (BDE-209) on cats

  Khidkhan K, Mizukawa H, Ikenaka Y, Nakayama SMM, Nomiyama K, Yokoyama N, Ichii O, Takiguchi M, Tanabe S, Ishizuka M

  PLOS ONE 18 1 e0277689  2023年01月 [査読有り]
   

  As an animal familiar to humans, cats are considered to be sensitive to chemicals; cats may be exposed to polychlorinated biphenyls (PCBs) and decabromodiphenyl ether (BDE-209) from indoor dust, household products, and common pet food, leading to adverse endocrine effects, such as thyroid hormone dysfunction. To elucidate the general biological effects resulting from exposure of cats to PCBs and PBDEs, cats were treated with a single i.p. dose of a principal mixture of 12 PCBs and observed for a short-term period. Results revealed that the testis weight, serum albumin, and total protein of the treated group decrease statistically in comparison with those in the control group. The negative correlations suggested that the decrease in the total protein and albumin levels may be disturbed by 4'OH-CB18, 3'OH-CB28 and 3OH-CB101. Meanwhile, the serum albumin level and relative brain weight decreased significantly for cats subjected to 1-year continuous oral administration of BDE-209 in comparison to those of control cats. In addition, the subcutaneous fat as well as serum high-density lipoprotein (HDL) and triglycerides (TG) levels increased in cats treated with BDE-209 and down-regulation of stearoyl-CoA desaturase mRNA expression in the liver occurred. These results suggested that chronic BDE-209 treatment may restrain lipolysis in the liver, which is associated with lipogenesis in the subcutaneous fat. Evidence of liver and kidney cell damage was not observed as there was no significant difference in the liver enzymes, blood urea nitrogen and creatinine levels between the two groups of both experiments. To the best of our knowledge, this is the first study that provides information on the biochemical effects of organohalogen compounds in cats. Further investigations on risk assessment and other potential health effects of PCBs and PBDEs on the reproductive system, brain, and lipid metabolism in cats are required.
• An experimental challenge model for Leishmania donovani in beagle dogs, showing a similar pattern of parasite burden in the peripheral blood and liver.

  Hiroya Konno, Nozomu Yokoyama, Yu Tamura, Keisuke Aoshima, Ryo Nakao, Mitsuyoshi Takiguchi, Ken Katakura

  Parasitology research 121 12 3569 - 3579 2022年12月 [査読有り]
   

  Leishmania donovani and Leishmania infantum are closely related species. However, the former is considered the causative agent for anthroponotic visceral leishmaniasis (AVL), while the latter is known to be responsible for zoonotic visceral leishmaniasis (ZVL) with dogs as the main reservoir host. Although molecular detection of L. donovani from naturally infected dogs has been reported in AVL endemic areas, the experimental infection of dogs with this species is very limited. Here, we constructed an experimental canine visceral leishmaniasis (CVL) model with L. donovani infection using beagle dogs. During an observation period of 8 months after parasite inoculation, few clinical symptoms were observed in the three inoculated dogs. The overall hematological and biochemical data of the dogs showed normal levels, and there were no remarkable changes in the peripheral CD4+, CD8+, CD25+, or FoxP3+ T cell populations. Liver biopsy sampling was conducted to monitor the parasite burden in the liver. A similar pattern of the amount of mitochondrial kinetoplast DNA was observed in the peripheral blood and liver by real-time PCR analysis. In addition, parasite antigens were detected from the liver biopsy sections by immunohistochemical analysis, further supporting the existence of parasites in the liver. These results showed a subclinical CVL model for L. donovani in beagle dogs with a similar kinetics of parasite burden in the peripheral blood and liver.
• Health impact assessment of pet cats caused by organohalogen contaminants by serum metabolomics and thyroid hormone analysis.

  Kei Nomiyama, Yasuo Yamamoto, Akifumi Eguchi, Hiroyuki Nishikawa, Hazuki Mizukawa, Nozomu Yokoyama, Osamu Ichii, Mitsuyoshi Takiguchi, Shouta M M Nakayama, Yoshinori Ikenaka, Mayumi Ishizuka

  The Science of the total environment 842 156490 - 156490 2022年10月10日 [査読有り]
   

  Companion animals are in close contact with the human surroundings, and there is growing concern about the effects of harmful substances on the health of pet cats. In this study, we investigated the potential health effects of organohalogen compounds (OHCs) on thyroid hormone (TH) homeostasis and metabolomics in Japanese pet cats. There was a significant negative correlation between concentrations of several contaminants, such as polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), hydroxylated PCBs (OH-PCBs), hydroxylated PBDEs (OH-PBDEs), and THs in cat serum samples. These results suggested that exposure to OHCs causes a decrease in serum TH levels in pet cats. In this metabolomics study, each exposure level of parent compounds (PCBs and PBDEs) and their hydroxylated compounds (OH-PCBs and OH-PBDEs) were associated with their own unique primary metabolic pathways, suggesting that parent and phenolic compounds exhibit different mechanisms of action and biological effects. PCBs were associated with many metabolic pathways, including glutathione and purine metabolism, and the effects were replicated in in-vivo cat PCB administration studies. These results demonstrated that OHC exposure causes chronic oxidative stress in pet cats. PBDEs were positively associated with alanine, aspartate, and glutamate metabolism. Due to the chronic exposure of cats to mixtures of these contaminants, the combination of their respective metabolic pathways may have a synergistic effect.
• Local cerebral blood flow assessment using transcranial Doppler ultrasonography in a dog with brain infarction in the right middle cerebral artery territory.

  Kazuyoshi Sasaoka, Hiroshi Ohta, Tomohito Ishizuka, Tatsuyuki Osuga, Keitaro Morishita, Noboru Sasaki, Mitsuyoshi Takiguchi

  The Journal of veterinary medical science 84 10 1385 - 1390 2022年10月01日 [査読有り]
   

  A 12-year-old neutered male Chihuahua was diagnosed with acute brain infarction in the right middle cerebral artery (MCA) territory. Transcranial Doppler ultrasonography (TCD) was performed to assess the local cerebral blood flow at the time of diagnosis and after 4 and 31 hr. Initially, the right MCA retained blood flow but with a lower cerebral blood flow velocity (CBFV; 14.9 cm/sec) than the left MCA (27.9 cm/sec). The TCD vascular resistance variables were higher in the right than in the left MCA. An increase in the CBFV and a decrease in TCD vascular resistance variables were observed, consistent with improvements in neurological symptoms. TCD can be a non-invasive, and easy-to-use modality for bedside monitoring of cerebral edema and infarction.
• Malignant oligoastrocytoma in the spinal cord of a cat.

  Dai Hasegawa, Keisuke Aoshima, Kazuyoshi Sasaoka, Atsushi Kobayashi, Mitsuyoshi Takiguchi, Takashi Kimura

  The Journal of veterinary medical science 84 9 1277 - 1282 2022年09月12日 [査読有り]
   

  A 12-year and 3-month spayed female mixed cat was presented with severe lumbar pain. Magnetic resonance imaging and postmortem examination revealed a swollen lesion in the spinal cord at L3 level. Histologic examination identified extensive neoplastic cell proliferation with massive necrosis in the tumor tissue. Two types of neoplastic cells were recognized. One type of neoplastic cells were large cells characterized by round to polygonal shape and abundant eosinophilic cytoplasm (referred to as "large cells"). The other neoplastic cells were small, densely proliferated, and had round to irregular shape and scant eosinophilic cytoplasm (referred to as "small cells"). Both types of cells were positive for oligodendrocyte transcription factor 2 and SRY-box transcription factor 10. Glial fibrillary acidic protein was positive in large cells but negative in most small cells. Digital analysis for Ki-67-stained tumor tissues found that total 21.1% ± 6.5% of tumor cells were positive for Ki-67. Based on these findings, we diagnosed malignant oligoastrocytoma in the spinal cord.
• Urinary corticoid to creatinine ratios using IMMULITE 2000 XPi for diagnosis of canine hypercortisolism.

  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 84 7 954 - 959 2022年07月10日 [査読有り]
   

  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.
• Characterization of mucin gene expression and goblet cell proportion in inflammatory colorectal polyps in miniature dachshunds.

  Noriyuki Nagata, Hiroshi Ohta, Nozomu Yokoyama, Yong Bin Teoh, Noboru Sasaki, Kensuke Nakamura, Mitsuyoshi Takiguchi

  The Journal of veterinary medical science 84 6 872 - 876 2022年06月18日 [査読有り]
   

  Hyperplastic goblet cells and abundant mucus are significant characteristics of inflammatory colorectal polyps (ICRPs) in miniature dachshunds. In this study, selected mucin gene expressions and goblet cell proportions were evaluated in miniature dachshunds with ICRPs and in healthy dogs. Mucin 2 (MUC2) gene expression was not significantly different among the groups, whereas mucin 5AC (MUC5AC) gene expression was significantly higher in the polypoid lesions than in healthy colonic mucosa. Although the percentage of goblet cells in the upper crypt regions did not significantly differ between the groups, that in the lower crypt regions was significantly decreased in polypoid lesions. In conclusion, increased MUC5AC gene expression and goblet cell proportion changes may be associated with the pathogenesis of ICRPs.
• Incremental predictive value of echocardiographic indices of right ventricular function in the assessment of long-term prognosis in dogs with myxomatous mitral valve disease

  T. Morita, K. Nakamura, T. Osuga, M. Takiguchi

  Journal of Veterinary Cardiology 39 51 - 62 2022年02月 [査読有り]
   

  Introduction: Few studies have evaluated the utility of echocardiographic indices of right ventricular (RV) function in predicting prognosis in dogs with myxomatous mitral valve disease (MMVD). Animals: Sixty-seven client-owned dogs were diagnosed with MMVD. Materials and methods: clinical cohort study. Dogs diagnosed with American college of veterinary internal medicine (ACVIM) stage B2, C or D between April 2014 and March 2017 were enrolled. Long-term outcomes were assessed by telephone or from the medical record. The primary end-point was defined as cardiac-related death. Echocardiographic indices of RV function, including the RV Tei index, free wall and septal RV longitudinal strain, were obtained. Univariable and multivariable Cox proportional hazard analyses were used to identify variables predictive of cardiac-related death. Results: Twenty-four dogs died during the follow-up period. The median follow-up time was 482 days, and the median survival time for dogs with cardiac-related death was 230 days. For cardiac-related death, peak early diastolic mitral inflow velocity, ACVIM stage C or D, tricuspid regurgitation velocity, RV Tei index and RV end-diastolic area were predictors in univariable Cox proportional hazard analysis. In multivariable Cox proportional analysis adjusted for the left atrial to aorta ratio, peak early diastolic mitral inflow velocity and ACVIM stage, an increase in the Tei index by 0.1 increased the hazard ratio of cardiac-related death by 33% (95% confidence interval, 16–70%; P = 0.002). Conclusions: In dogs with MMVD, RV dysfunction assessed by the Tei index is an independent predictor of cardiac-related death.
• Transcranial Doppler ultrasonography detects the elevation of cerebral blood flow during ictal-phase of pentetrazol-induced seizures in dogs.

  Kazuyoshi Sasaoka, Hiroshi Ohta, Tomohito Ishizuka, Kazuki Kojima, Noboru Sasaki, Mitsuyoshi Takiguchi

  American journal of veterinary research 83 4 331 - 338 2022年01月28日 [査読有り]
   

  OBJECTIVE: To investigate the association between changes in cerebral blood flow and electrographic epileptic seizure in dogs using transcranial Doppler ultrasonography (TCD). ANIMALS: 6 healthy Beagle dogs. PROCEDURES: Each dog was administered pentetrazol (1.5 mg/kg/min) or saline (0.9% NaCl) solution under general anesthesia with continuous infusion of propofol. Both pentetrazol and saline solution were administered to all 6 dogs, with at least 28 days interval between the experiments. Blood flow waveforms in the middle cerebral artery and the basilar artery were obtained using TCD at baseline, after pentetrazol administration, and after diazepam administration. TCD velocities, including peak systolic velocity, end-diastolic velocity, and mean velocity and resistance variables, were determined from the Doppler waveforms. RESULTS: During ictal-phase of pentetrazol-induced seizures, the TCD velocities significantly increased in the basilar and middle cerebral arteries while TCD vascular resistance variables did not change in either artery. The TCD velocities significantly decreased after diazepam administration. Systemic parameters, such as the heart rate, mean arterial pressure, systemic vascular resistance, cardiac index, end-tidal carbon dioxide, oxygen saturation, and body temperature, did not change significantly during seizures. CLINICAL RELEVANCE: This study showed that cerebral blood flow, as obtained from TCD velocities, increased by 130% during ictal-phase of pentetrazol-induced seizures in dogs. The elevated velocities returned to baseline after seizure suppression. Thus, TCD may be used to detect electrographic seizures during the treatment of status epilepticus in dogs, and further clinical studies clarifying the association between changes in cerebral blood flow and non-convulsive seizure cases are needed.
• Serum steroid profiling of hepatocellular carcinoma associated with hyperadrenocorticism in dogs: A preliminary study.

  Thandar Oo, Noboru Sasaki, Yoshinori Ikenaka, Takahiro Ichise, Noriyuki Nagata, Nozomu Yokoyama, Kazuyoshi Sasaoka, Keitaro Morishita, Kensuke Nakamura, Mitsuyoshi Takiguchi

  Frontiers in veterinary science 9 1014792 - 1014792 2022年 [査読有り]
   

  BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common primary liver tumors in humans and dogs. Excessive adrenocortical hormone exposure may cause steroid hepatopathy, which may develop into HCC. In our previous study, hyperadrenocorticism (HAC) was a highly concurrent disease in dogs with HCC. Therefore, this study hypothesized that adrenal steroid alterations might be involved in hepatocarcinogenesis and aimed to specify the relationship between HAC and HCC in dogs. MATERIALS AND METHODS: This study included 46 dogs brought to the Hokkaido University Veterinary Teaching Hospital between March 2019 and December 2020. Owners gave their signed consent for blood collection on their first visit. A total of 19 steroids (14 steroids and 5 metabolites) in the baseline serum of 15 dogs with HCC, 15 dogs with HAC, and 10 dogs with both diseases were quantitatively measured using the developed liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS) method. RESULTS: In each group, 11 steroids were detected higher than 50%. The detection rate of steroid hormones did not significantly differ between the groups (p > 0.05). Principle component analysis (PCA) showed that the steroid profiles of the three groups were comparable. Median steroid hormone concentrations were not significantly different between the study diseases (p > 0.05). CONCLUSION: The developed LC/MS/MS was useful for measuring steroid hormones. Although it was clear that HAC was concurrent in dogs with HCC, none of the serum steroids was suggested to be involved in HCC.
• Evaluation of Right Ventricular Function and Dyssynchrony in a Dog Model of Acute Pulmonary Embolism: Diagnostic Utility and Reversibility.

  Tomoya Morita, Kensuke Nakamura, Tatsuyuki Osuga, Sei Kawamoto, Shingo Miki, Mitsuyoshi Takiguchi

  Frontiers in veterinary science 9 861064 - 861064 2022年 [査読有り]
   

  Background: The diagnosis of acute pulmonary thromboembolism is challenging in dogs. Little has been reported on changes in echocardiographic indices in dogs with acute pulmonary thromboembolism. The objective of this study was to validate the relationship between echocardiographic indices and right heart catheterization variables in dogs with acute pulmonary embolism and to identify a useful echocardiographic index for diagnosing acute pulmonary embolism. Materials and Methods: Six healthy laboratory beagles were included in the study. Echocardiography and right heart catheterization were performed in a dog model of acute pulmonary embolism produced by microsphere injection. Echocardiographic indices, including the right ventricular (RV) Tei index, RV longitudinal strain, and the dyssynchrony index using speckle tracking echocardiography, transmitral flow, and eccentricity index, were measured. Results: The mean pulmonary arterial pressure increased (22.2 ± 1.2 mmHg) and the blood pressure decreased after microsphere injection. Although the mean pulmonary arterial pressure remained elevated, the blood pressure recovered 2 days after the microsphere injection. Most echocardiographic indices of RV function were significantly impaired following microsphere injection and recovered after 2 days. In contrast, the RV Tei index was significantly impaired after microsphere injection and the impairment persisted after 2 days. Multivariable analysis revealed that the RV Tei index was an independent echocardiographic predictor of pulmonary vascular resistance (β = 0.88, P < 0.001), and transmitral early diastolic wave was an independent predictor of the cardiac index (β = -0.86, P = 0.001). Conclusions: The RV Tei index is a useful echocardiographic index for diagnosing acute pulmonary embolism. Ventricular interdependence may be an important factor causing low cardiac output in dogs with acute pulmonary embolism.
• Case Report: Usefulness of Drip Infusion Cholangiography With Computed Tomography for the Diagnosis of Biloma in a Dog.

  Masahiro Tamura, Hiroshi Ohta, Nene Hasegawa, Kenji Hosoya, Mitsuyoshi Takiguchi

  Frontiers in veterinary science 9 854042 - 854042 2022年 [査読有り]
   

  Bilomas are encapsulated collections of bile outside or inside the biliary tract within the abdominal cavity. For diagnostic and therapeutic approaches, it is important to identify the origin of bile leaks from the biliary tract. This case report describes the usefulness of drip infusion cholangiography with computed tomography (DIC-CT) for detecting the site of bile leakage in a dog with biloma. A 10-year-old, castrated male Pomeranian dog was referred to our department for gastrointestinal signs. Abdominal ultrasonography detected gallbladder mucocele without evidence of defect on the wall and well-defined anechoic localized fluid accumulation around the right division of the liver. On the other hand, there was only a small amount of ascites in the abdominal cavity. The accumulated fluid collected through abdominocentesis had a bilirubin concentration of 11.4 mg/dl, which was more than twice as high as that in serum (0.4 mg/dl), but had absence of pyogenic bacteria. The DIC-CT with meglumine iotroxate showed two well-defined large fluid collections: one between right medial and lateral lobe and the other between the right lateral lobe and caudate process of caudate lobe. Three-dimensional DIC-CT views that the former was enhanced by the contrast agent and that it communicated with an intrahepatic bile duct of the right lateral lobe. Moreover, the DIC-CT images confirmed communication with each fluid collections. After 6 days of hospitalization, a decrease in the amount of accumulated fluid was confirmed, after which cholecystectomy was performed. The dog was discharged from the hospital without complications. No signs of bile leakage were observed on follow-up imaging on postoperative day 10. According to authors knowledge, this has been the first report to show that DIC-CT can be useful for determining the origin of bile leakage in dogs with bilomas.
• Safety Assessment of Ultrasound-Assisted Intravesical Chemotherapy in Normal Dogs: A Pilot Study.

  Noboru Sasaki, Yoshinori Ikenaka, Keisuke Aoshima, Teiichiro Aoyagi, Nobuki Kudo, Kensuke Nakamura, Mitsuyoshi Takiguchi

  Frontiers in pharmacology 13 837754 - 837754 2022年 [査読有り]
   

  Intravesical chemotherapy after transurethral resection is a treatment option in patients with non-muscle invasive bladder cancer. The efficacy of intravesical chemotherapy is determined by the cellular uptake of intravesical drugs. Therefore, drug delivery technologies in the urinary bladder are promising tools for enhancing the efficacy of intravesical chemotherapy. Ultrasound-triggered microbubble cavitation may enhance the permeability of the urothelium, and thus may have potential as a drug delivery technology in the urinary bladder. Meanwhile, the enhanced permeability may increase systemic absorption of intravesical drugs, which may increase the adverse effects of the drug. The aim of this preliminary safety study was to assess the systemic absorption of an intravesical drug that was delivered by ultrasound-triggered microbubble cavitation in the urinary bladder of normal dogs. Pirarubicin, a derivative of doxorubicin, and an ultrasound contrast agent (Sonazoid) microbubbles were administered in the urinary bladder. Ultrasound (transmitting frequency 5 MHz; pulse duration 0.44 μsec; pulse repetition frequency 7.7 kHz; peak negative pressure -1.2 MPa) was exposed to the bladder using a diagnostic ultrasound probe (PLT-704SBT). The combination of ultrasound and microbubbles did not increase the plasma concentration of intravesical pirarubicin. In addition, hematoxylin and eosin staining showed that the combination of ultrasound and microbubble did not cause observable damages to the urothelium. Tissue pirarubicin concentration in the sonicated region was higher than that of the non-sonicated region in two of three dogs. The results of this pilot study demonstrate the safety of the combination of intravesical pirarubicin and ultrasound-triggered microbubble cavitation, that is, ultrasound-assisted intravesical chemotherapy.
• Prognostic value of left ventricular-arterial coupling estimated using echocardiography in dogs with myxomatous mitral valve disease.

  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.
• The use of 4-dimensional magnetic resonance angiography as a noninvasive procedure to diagnose subclavian steal syndrome in a dog.

  Genya Shimbo, Ryosuke Echigo, Mitsuyoshi Takiguchi

  Journal of the American Veterinary Medical Association 259 9 1040 - 1042 2021年11月01日 [査読有り]
   

  CASE DESCRIPTION: A 5-year-old 4.1-kg (9.0-lb) spayed female Toy Poodle was referred because of a 6-month history of sporadic signs of neck pain. CLINICAL FINDINGS: Diagnostic imaging with MRI and CT revealed a dilated radicular artery connecting the right and left vertebral arteries and causing mild compression of the spinal cord. The left subclavian artery caudal to the origin of the left vertebral artery was absent. Subclavian steal syndrome (SSS) was suspected. TREATMENT AND OUTCOME: The owner declined surgical treatment; thus, the dog was treated conservatively with glucocorticoids and analgesics. Eight months later, the dog's clinical signs were unchanged but palliated with the administration of glucocorticoids and analgesics, and 4-dimensional (4-D) magnetic resonance angiography (MRA) revealed that the left vertebral artery received blood supply from the right vertebral artery through the dilated radicular artery and that the left vertebral artery caudal to this site had retrograde flow and drained into the left subclavian artery, confirming the diagnosis of SSS. The owner again declined surgery, and conservative treatment continued. The dog's condition was unchanged at the last follow-up communication 11 months after 4-D MRA. CLINICAL RELEVANCE: Subclavian steal syndrome is an extremely rare condition in dogs, and our findings suggested that 4-D MRA could be used to definitively diagnose SSS in dogs.
• Effects of intravenous administration of pimobendan on hemodynamic indices and indices of left atrial longitudinal strain derived from speckle-tracking echocardiography in healthy dogs.

  Shingo Miki, Kensuke Nakamura, Tomoya Morita, Tatsuyuki Osuga, Sei Kawamoto, Noboru Sasaki, Mitsuyoshi Takiguchi

  American journal of veterinary research 82 10 795 - 801 2021年10月 [査読有り]
   

  OBJECTIVE: To determine the effects of IV administration of pimobendan on hemodynamic indices and indices of left atrial (LA) longitudinal strain by speckle-tracking echocardiography in healthy dogs. ANIMALS: 6 healthy Beagles. PROCEDURES: After the dogs were anesthetized, the right heart was catheterized and 2-D conventional and speckle-tracking echocardiography were performed before and after IV administration of 0.15 mg of pimobendan/kg. Speckle-tracking echocardiography was performed to assess the 3 LA phasic functions through LA deformation (longitudinal strain and strain rate) and volumetric analyses. RESULTS: Pimobendan significantly increased stroke volume and cardiac output and decreased systemic vascular resistance. Pimobendan significantly improved left ventricular function assessed by the Tei index and LA booster pump function assessed by LA longitudinal strain and change in fractional volume during atrial systole. Indices of LA reservoir and conduit function were unchanged. CONCLUSIONS AND CLINICAL RELEVANCE: In healthy dogs, IV administration of pimobendan improved the indices of LA booster pump function but had no effect on the indices of LA reservoir and conduit functions. Further studies are needed to validate whether these results can be extrapolated to dogs with myxomatous mitral valve disease.
• Genome-wide DNA methylation analysis of dogs with high lead exposure living near a lead mining area in Kabwe, Zambia.

  Jumpei Yamazaki, Haruya Toyomaki, Shouta M M Nakayama, John Yabe, Kaampwe Muzandu, Jaroslav Jelinek, Shoko Yokoyama, Yoshinori Ikenaka, Mitsuyoshi Takiguchi, Mayumi Ishizuka

  Environmental pollution (Barking, Essex : 1987) 286 117229 - 117229 2021年10月01日 [査読有り]
   

  Lead (Pb) is a heavy metal that has been proven to be toxic to both animals and humans. Genom-wide DNA methylation in domestic dogs exposed to high levels of Pb in Kabwe, Zambia was analyzed in this study. Using next-generation sequencing on samples from 20 domestic dogs (mean blood Pb concentration: 43.6 μg/dL and 7.2 μg/dL in the high and low exposure groups), a digital restriction enzyme analysis of methylation was performed to identify the genomic locations of differentially methylated CpG sites. A validation study on an additional 20 dogs followed (blood Pb concentration: 4.9-29.7 μg/dL). The cluster analysis resolved two broad clusters indicating high and low Pb exposure. The study identified 827 (1.2%) CpG sites with differences in methylation (101 CpG sites were hypermethylated in the low exposure group and 726 were hypermethylated in the high exposure group). The sites corresponded to 26 genes with differentially methylated CpG sites at their promoter regions, including the NGF gene. The methylation of four CpG sites was validated using bisulfite pyrosequencing. The results indicate that aberrant hypermethylation is prevalent in dogs exposed to Pb. The altered DNA methylation of the genes identified in this study contributes to a greater understanding of the epigenetic changes caused by Pb exposure and highlights novel biomarker discoveries across species.
• Obese status is associated with accelerated DNA methylation change in peripheral blood of senior dogs.

  Jumpei Yamazaki, Shinji Meagawa, Jaroslav Jelinek, Shoko Yokoyama, Noriyuki Nagata, Masashi Yuki, Mitsuyoshi Takiguchi

  Research in veterinary science 139 193 - 199 2021年10月 [査読有り]
   

  Obesity and its associated comorbidities constitute a major and growing health problem worldwide not only involved with people but also dogs and cats. Although few genetic mutations have been associated with obesity in dogs, molecular mechanism remains to be clearly understood. Given the fact that DNA methylation leads to gene expression variability and has plasticity affected by metabolic phenotypes such as obesity in human, the objective of this study is to identify obesity-associated differentially methylated cytosine-phosphate-guanine (CpG) dinucleotide sites in dogs. With genome-wide DNA methylation analysis using next-generation sequencing for blood samples from fourteen Miniature dachshunds with body condition score (BCS) 4-5 and BCS ≥6, over 100,000 sites could be analysed to identify genomic locations of differentially methylated CpG sites. As a result, 191 differentially methylated CpG sites (89 CpG sites were hypermethylated in BCS ≥6 and 102 were hypermethylated in BCS 4-5) were identified. These sites included promoter regions of Kisspeptin receptor (KISS1R) and Calcyphosine 2 (CAPS2) genes which were subsequently validated by bisulfite-pyrosequencing for another set of 157 dog blood samples. KISS1R methylation levels were found to be higher in BCS ≥6 group than BCS 4-5 in senior (>84 months) dogs. Especially male dogs but not female dogs as well as uncastrated male dogs but not castrated male dogs showed this trend. DNA methylation of KISS1R gene will be useful for understanding of comprehensive epigenetic change in obese dogs.
• Simultaneous steroids measurement in dogs with hyperadrenocorticism using a column-switching liquid chromatography-tandem mass spectrometry method.

  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 [査読有り]
   

  We developed an analytical method using an on-line column-switching liquid chromatography with triple quadrupole mass spectrometry (LC/MS/MS) for quantifying multiple steroids in serum. Using the developed method, we evaluated the serum concentration of nine steroids (cortisol, corticosterone, cortisone, 11-deoxycortisol, 21-deoxycortisol, deoxycorticosterone, progesterone, 17α-OH-progesterone and aldosterone) in dogs with hyperadrenocorticism (HAC). Serum was mixed with stable isotope internal standards and thereafter purified by the automated column-switching system. The limit of detection ranged 2-16 pg/ml for nine steroids. In the baseline samples, five steroids (cortisol, corticosterone, cortisone, 11-deoxycortisol, and 17α-OH-progesterone) were detected in all dogs. The concentrations of cortisone, 11-deoxycortisol, and 17α-OH-progesterone in dogs with HAC (n=19) were significantly higher those in dogs without HAC (n=15, P<0.02). After the adrenocorticotropic hormone stimulation test, six steroids (cortisol, corticosterone, cortisone, 11-deoxycortisol, 17α-OH-progesterone, and deoxycorticosterone) were above the limit of quantification in all dogs. Cortisol, corticosterone, cortisone, and deoxycorticosterone concentrations of dogs with HAC were significantly higher than those of dogs without HAC (P<0.02). In addition, 11-deoxycortisol and 17α-OH-progesterone concentration was higher in dogs with HAC than in dogs without HAC (P=0.044 and P=0.048, respectively). The on-line column-switching LC/MS/MS would be feasible for measuring multiple steroids in dog serum. The results suggest that cortisone, 11-deoxycortisol, and 17α-OH-progesterone would be related to HAC. Further studies are warranted to assess the clinical feasibility of steroid profile in dogs with HAC.
• Genome-wide DNA methylation profile in feline haematological tumours: A preliminary study.

  Jumpei Yamazaki, Jaroslav Jelinek, Shoko Yokoyama, Mitsuyoshi Takiguchi

  Research in veterinary science 140 221 - 228 2021年09月08日 [査読有り]
   

  Although DNA methylation has been analysed in few studies for a limited number of loci in cats with diseases, genome-wide profile of DNA methylation has never been addressed. The hypothesis for this study is that next-generation sequencing with sequential digestion of genomic DNA with SmaI and XmaI enzymes could provide highly quantitative information on methylation levels in cats. Using blood from four healthy control cats and two disease cats as well as three feline lymphoma/leukemia cell lines, approximately 74-94 thousand CpG sites across the cat genome could be analysed. CpG sites in CpG island (CGI) were broadly either methylated or unmethylated in normal blood, while CpG sites in non-CpG islands (NCGI) are largely methylated. Lymphoma cell lines showed thousands of CpG sites with gain of methylation at normally unmethylated CGI sites and loss of methylation at normally methylated NCGI sites. Hypermethylated CpG sites located at promoter regions included genes annotated with 'developmental process' and 'anatomical structure morphogenesis' such as HOXD10. This highly quantitative method would be suitable for studies of DNA methylation changes not only in cancer but also in other common diseases in cats.
• Systemic mucoid degeneration of the arterial tunica intima in a young dog.

  Yoshiki Ichikawa, Mizuki Heishima, Kristin Vyhnal, Keisuke Aoshima, Kazuyoshi Sasaoka, Ryohei Kinoshita, Atsushi Kobayashi, Mitsuyoshi Takiguchi, Takashi Kimura

  Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc 34 1 10406387211042587 - 10406387211042587 2021年09月04日 [査読有り]
   

  A 27-mo-old, spayed female mixed-breed dog was presented with left forelimb pain, which progressed to full thickness necrosis of the soft tissues of multiple limbs. Clinical imaging and postmortem examination suggested multiple large arterial thromboemboli. Histologic examination of vascular lesions revealed markedly thickened tunica intima with polypoid intraluminal projections, which partially to entirely occluded the arterial lumen. The expanded tunica intima was comprised of intimal accumulation of Alcian blue-positive matrix with scattered spindle-to-satellite cells. These cells were positive for von Willebrand factor and vimentin but negative for α-smooth muscle actin, suggesting endothelial origin. Deposition of the intimal mucoid matrix was observed in the elastic and muscular arteries associated with regional ischemic changes. Mucoid emboli, likely from fragmentation of proliferative intimal tissue, were identified in smaller vessels supplied by affected arteries. Based on these findings, we diagnosed systemic mucoid degeneration of the arterial tunica intima. Such systemic arterial degeneration characterized by deposition of mucoid matrix in the tunica intima has not been reported previously in dogs, to our knowledge, and should be distinguished from thromboembolism and other degenerative vascular diseases.
• Cardiovascular effects of dose escalating of norepinephrine in healthy dogs anesthetized with isoflurane.

  Kazuki Kojima, Tomohito Ishizuka, Noboru Sasaki, Kensuke Nakamura, Mitsuyoshi Takiguchi

  Veterinary anaesthesia and analgesia 48 5 654 - 662 2021年09月 [査読有り]
   

  OBJECTIVE: To evaluate the systemic cardiovascular effects of dose escalating administration of norepinephrine in healthy dogs anesthetized with isoflurane. STUDY DESIGN: Experimental study. ANIMALS: A total of six adult laboratory Beagle dogs, 10.5 (9.2-12.0) kg [median (range)]. METHODS: Each dog was anesthetized with isoflurane at an end-tidal concentration of 1.7%, mechanically ventilated and administered a continuous rate infusion of rocuronium (0.5 mg kg-1 hour-1). Each dog was administered incremental dose rates of norepinephrine (0.05, 0.125, 0.25, 0.5, 1.0 and 2.0 μg kg-1 minute-1), and each dose was infused for 15 minutes. Cardiovascular variables were recorded before administration and at the end of each infusion period. RESULTS: Norepinephrine infusion increased mean arterial pressure (MAP), cardiac output (CO) and oxygen delivery in a dose-dependent manner. Systemic vascular resistance did not significantly change during the experiment. Stroke volume increased at the lower dose rates and heart rate increased at the higher dose rates. Oxygen consumption and lactate concentrations did not significantly change during infusions. CONCLUSIONS: In dogs anesthetized with isoflurane, norepinephrine increased MAP by increasing the CO. CO increased with a change in stroke volume at lower dose rates of norepinephrine. At higher dosage, heart rate also contributed to an increase in CO. Norepinephrine did not cause excessive vasoconstriction that interfered with the CO during this study. CLINICAL RELEVANCE: Norepinephrine can be useful for treating hypotension in dogs anesthetized with isoflurane.
• Peliosis Hepatis with Chylous Ascites in a Dog.

  Kevin Christian Montecillo Gulay, Noriyuki Nagata, Keisuke Aoshima, Nozomi Shiohara, Atsushi Kobayashi, Mitsuyoshi Takiguchi, Takashi Kimura

  Journal of comparative pathology 187 63 - 67 2021年08月 [査読有り]
   

  A 6-year-old spayed female Toy Poodle dog was referred to the Hokkaido University Veterinary Teaching Hospital for abdominal distension. Abdominocentesis yielded ascitic fluid that had a mildly increased total protein concentration and a 2.7-fold higher triglyceride concentration than plasma, and was interpreted as chylous ascites. The patient had an enlarged liver, which contained multiple, small, nodular masses and cyst-like structures. Microscopically, these lesions were multifocal dilated spaces containing lymphocytes, endothelial cells, fibrin and islands of hepatocytes. Increased α-smooth muscle actin-positive cells were observed in hepatic sinusoids. Based on these findings, we diagnosed peliosis hepatis with chylous ascites, which is likely to have been due to lymphangiectasia and disrupted hepatic sinusoids. Neither Bartonella spp DNA nor mutations in ACVRL1 and MTM1 genes were detected, although there was a 47-fold increase in hepatic ACVRL1 expression compared with age-matched control liver. To the authors' knowledge, this is the first report of chylous ascites resulting from peliosis hepatis in any species.
• CT morphology of anomalous systemic arterial supply to normal lung in dogs.

  Genya Shimbo, Mitsuyoshi Takiguchi

  Veterinary radiology & ultrasound : the official journal of the American College of Veterinary Radiology and the International Veterinary Radiology Association 62 6 657 - 665 2021年07月11日 [査読有り]
   

  Anomalous systemic arterial supply to the normal lung (ASANL) is a rare congenital anomaly in humans, in which the systemic arteries supply the basal segments of the lower lobe. It has a normal bronchial connection, but lacks a normal pulmonary artery. This anomaly has not been previously reported in the veterinary literature. The objectives of this retrospective descriptive study were to characterize the CT findings and clinical features of ASANL , and to determine the breed predisposition in a population of referral canine cases. Thoracic CT images, in which the caudal lung lobes were fully inflated and the pulmonary artery could be traced to the periphery, were reviewed. A total of 1,950 dogs were enrolled, and the aberrant vasculature equivalent to ASANL in humans was detected in 48 dogs. Shetland Sheepdogs (7/48, odds ratio [OR] = 8.0, P < 0.00001), Miniature Dachshunds (19/48, OR = 3.9, P < 0.00001), and Labrador Retrievers (6/48, OR = 4.5, P = 0.0009) were over-represented. The affected lung lobes were the right caudal lobe (24/48, 50%), the left caudal lobe (21/48, 43.8%), and bilateral caudal lobes (3/48, 6.3%). The aberrant vessels originated from the left gastric artery (14/48), descending thoracic aorta (8/48), celiac artery (6/48), and splenic artery (1/48). In the remaining 19 cases, the origin of the aberrant vessels could not be determined. Although the clinical significance of ASANL in dogs remains unclear, surgeons should be aware of this finding prior to lobectomy of the caudal lung lobes to avoid intraoperative systemic arterial bleeding.
• Morphometric evaluation of canine hepatocellular carcinoma using computed tomography: a promising tool for predicting malignancy.

  Rommaneeya Leela-Arporn, Hiroshi Ohta, Genya Shimbo, Noboru Sasaki, Mitsuyoshi Takiguchi

  The Journal of veterinary medical science 83 9 1459 - 1464 2021年07月06日 [査読有り]
   

  The size of canine focal liver lesions (FLLs) is known to be one of the predicting criteria for malignancy. However, there are discrepancies for the measurement of maximum lesion size, resulting in contradicting results among studies and incidences of false positive outcomes. Thus far, the morphometric changes of FLLs for distinguishing malignancy from benignancy remains undocumented. This study aimed to investigate morphometric characteristics of FLLs using computed tomography (CT). CT images of 40 dogs with histopathological confirmation of 49 liver lesions, including 39 hepatocellular carcinomas and 10 nodular hyperplasias were retrospectively reviewed. The morphometric parameters including size (long and short axis diameters measured on transverse image), shape (measured by long to short axis (L/S) ratio), volume, and surface appearance of a liver lesion were evaluated using univariate and stepwise multivariate analyses, respectively. The results of univariate analysis showed that long and short axis diameters, L/S ratio, volume, and surface appearance of a lesion were significantly different between hepatocellular carcinomas and nodular hyperplasias. Multivariate analysis revealed that short axis diameter (>3.30 cm; odds ratio (OR): 36.1, 95% confidence interval (CI): 3.36-387.05, P=0.0031) and L/S ratio (>1.23; OR: 18.1, 95% CI: 1.61-205.12, P=0.0191) were independent predictors of malignancy, with the area under the curve of 0.9154. These results suggest that the combination of short axis diameter and L/S ratio is a promising tool for predicting liver malignancy with outstanding discriminating ability.
• Extrahepatic biliary obstruction can interfere with hepatic fibrosis prediction using two-dimensional shear wave elastography in dogs.

  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 [査読有り]
   

  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.
• The effects of fipronil on emotional and cognitive behaviors in mammals.

  Tomohiro Suzuki, Anri Hirai, Kraisiri Khidkhan, Collins Nimako, Takahiro Ichise, Kazuki Takeda, Hazuki Mizukawa, Shouta M M Nakayama, Kei Nomiyama, Nobuhiko Hoshi, Mizuki Maeda, Tetsushi Hirano, Kazuyoshi Sasaoka, Noboru Sasaki, Mitsuyoshi Takiguchi, Mayumi Ishizuka, Yoshinori Ikenaka

  Pesticide biochemistry and physiology 175 104847 - 104847 2021年06月 [査読有り]
   

  Fipronil is a phenylpyrazole insecticide that is widely used as a pesticide and a veterinary drug, although studies suggest that it could be toxic to mammals. The objectives of this study were to examine the pharmacokinetic profile of fipronil in mice, dogs, and cats, and to evaluate its effects on emotional and cognitive behaviors of dogs and cats using the data obtained from mice. The assessment of in vivo kinetics of fipronil was conducted in mice and dogs. We also performed behavioral tests (elevated plus-maze and Y-maze) and measured the levels of neurotransmitters in mice exposed to fipronil. In addition, the in vitro metabolism of fipronil were evaluated using liver microsomes of rats, mice, dogs, and cats. The results revealed that fipronil is distributed throughout the body (blood, brain, adipose tissue, and liver) of mice after dermal application. It was metabolized to fipronil sulfone primarily in the liver. The data on kinetics show that both fipronil and fipronil sulfone have a longer half-life in dogs and cats than in mice. The behavioral tests indicated that fipronil and fipronil sulfone could affect emotional and cognitive behaviors and alter the levels of neurotransmitters (dopamine in the striatum and serotonin in the hippocampus) in mice. Furthermore, we found that dogs and cats have a low ability to metabolize fipronil than mice and rats. However, further comprehensive studies are needed to determine whether fipronil affects the emotional and cognitive behaviors when administered to dogs and cats. To the best of our knowledge, this is the first study to examine the pharmacokinetic data and verify the effects of fipronil on emotional and cognitive behaviors of dogs and cats using the data obtained from mice.
• DNA methylation landscape of 16 canine somatic tissues by methylation-sensitive restriction enzyme-based next generation sequencing.

  Jumpei Yamazaki, Yuki Matsumoto, Jaroslav Jelinek, Teita Ishizaki, Shingo Maeda, Kei Watanabe, Genki Ishihara, Junya Yamagishi, Mitsuyoshi Takiguchi

  Scientific reports 11 1 10005 - 10005 2021年05月11日 [査読有り]
   

  DNA methylation plays important functions in gene expression regulation that is involved in individual development and various diseases. DNA methylation has been well studied in human and model organisms, but only limited data exist in companion animals like dog. Using methylation-sensitive restriction enzyme-based next generation sequencing (Canine DREAM), we obtained canine DNA methylation maps of 16 somatic tissues from two dogs. In total, we evaluated 130,861 CpG sites. The majority of CpG sites were either highly methylated (> 70%, 52.5-64.6% of all CpG sites analyzed) or unmethylated (< 30%, 22.5-28.0% of all CpG sites analyzed) which are methylation patterns similar to other species. The overall methylation status of CpG sites across the 32 methylomes were remarkably similar. However, the tissue types were clearly defined by principle component analysis and hierarchical clustering analysis with DNA methylome. We found 6416 CpG sites located closely at promoter region of genes and inverse correlation between DNA methylation and gene expression of these genes. Our study provides basic dataset for DNA methylation profiles in dogs.
• Urinary free metanephrines measurement in dogs with adrenal gland diseases using a new simple liquid chromatography tandem mass spectrometry method.

  Noboru Sasaki, Yoshinori Ikenaka, Yumiko Inoue, Takahiro Ichise, Noriyuki Nagata, Mayumi Ishizuka, Syouta Mm Nakayama, Kensuke Nakamura, Mitsuyoshi Takiguchi

  The Journal of veterinary medical science 83 4 648 - 655 2021年04月09日 [査読有り]
   

  Measurement of urinary metanephrines in spot samples is used for the diagnosis of canine pheochromocytoma (PC). We describe a simple analytical method based on liquid chromatography tandem mass spectrometry (LC-MS/MS) for measuring free metanephrine (MN) and normetanephrine (NMN) in spot urine samples. Using the developed method, we evaluated the stability of urinary free-MN and free-NMN at various storing conditions. In addition, we assessed the feasibility of urinary free-MN and -NMN measurement for diagnosing PC. Urine samples were mixed with stable isotope internal standards and thereafter purified by ultrafiltration. The purified samples were analyzed by LC-MS/MS in the multiple reaction monitoring mode after separation on a multimode octa decyl silyl column. The coefficient of variation of free-MN and -NMN measurement was 7.6% and 5.5%, respectively. The linearity range was 0.5-10 µg/l for both analytes. Degradation was less than 10% for both analytes under any of the storage conditions. The median free-NMN ratio to creatinine of 9 PC dogs (595, range 144-47,961) was significantly higher (P<0.05) than that of 13 dogs with hypercortisolism (125, range 52-224) or 15 healthy dogs (85, range 50-117). The developed method is simple and may not require acidification of spot urine. The results of this preliminary retrospective study suggest that the measurement of urinary free metanephrines is a promising tool for diagnosing canine PC.
• Repeatability, reproducibility, and reference intervals for indices of right atrial longitudinal strain derived from speckle-tracking echocardiography in healthy dogs.

  Tomoya Morita, Kensuke Nakamura, Tatsuyuki Osuga, Mitsuyoshi Takiguchi

  American journal of veterinary research 82 4 274 - 279 2021年04月 [査読有り]
   

  OBJECTIVE: To determine repeatability, reproducibility, and reference intervals of indices of right atrial longitudinal strain (RALS) derived from speckle-tracking echocardiography (STE) in dogs without heart disease. ANIMALS: 110 client-owned dogs and 10 laboratory Beagles. PROCEDURES: To determine intraobserver within-day (repeatability) and interobserver (reproducibility) coefficients of variation, RALS during ventricular systole (ϵS), ventricular early diastole (ϵE), and atrial systole (ϵA), as derived with STE, were obtained by 2 investigators for 5 randomly selected client-owned dogs and analyzed by linear regression. Reference intervals were estimated from the results of all dogs. Correlations between RALS indices (ϵS, ϵE, and ϵA) and sex, age, body weight, heart rate, and blood pressure were determined. RESULTS: RALS derived from STE showed good intraobserver within-day repeatability and interobserver reproducibility, with coefficients of variation of < 20%. Both ϵS and ϵE were significantly negatively correlated with age, but ϵA was not correlated with age. Indices were not correlated with sex, body weight, or blood pressure. CONCLUSIONS AND CLINICAL RELEVANCE: RALS indices derived from STE were repeatable and reproducible and were affected by the age of dogs without heart disease. Age should be considered in the interpretation of RALS indices in clinical settings. Further studies are needed to apply RALS indices for assessing dogs with heart disease.
• Prognostic value of small intestinal dilatation in dogs with protein-losing enteropathy.

  Hiroshi Ohta, Noriyuki Nagata, Nozomu Yokoyama, Tatsuyuki Osuga, Noboru Sasaki, Keitaro Morishita, Mitsuyoshi Takiguchi

  The Journal of veterinary medical science 83 3 378 - 384 2021年03月11日 [査読有り]
   

  To date, little is known about the prognostic significance of ultrasonographic findings in dogs with protein-losing enteropathy (PLE). The aim of this retrospective study was to examine the prognostic value of ultrasonographic findings in dogs with PLE. A total of 26 dogs with PLE were included: 20 dogs with chronic enteropathy and 6 dogs with gastrointestinal lymphoma. The presence of small intestinal dilatation was associated with shorter survival time in dogs with PLE (P=0.003). The presence of hyperechoic intestinal mucosal striations was associated with longer survival time in dogs with PLE (P=0.0085). The results of the current study indicate that the presence of small intestinal dilatation might be associated with poor prognosis in dogs with PLE.
• Reduced expression levels of heat shock protein 90 in a diminazene aceturate-resistant Babesia gibsoni isolate.

  Masahiro Yamasaki, Natsuki Idaka, Moeko Abe, Mitsuyoshi Takiguchi

  Experimental parasitology 221 108050 - 108050 2021年02月 [査読有り]
   

  Heat shock protein 90 (HSP90) is a molecular chaperon and an essential component for stage differentiation and intracellular growth inside the host cells of many protozoans. HSP90 of Babesia gibsoni (BgHSP90) was suggested to function in the development of diminazene aceturate (DA)-resistance. Therefore, we examined the expression level of BgHSP90 in a DA-resistant B. gibsoni isolate. Transcription of the BgHSP90 gene in the DA-resistant isolate and wild-type B. gibsoni was assessed by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). As a result, the copy number and relative amount of BgHSP90 transcripts in the DA-resistant isolate were significantly lower than those in the wild-type. Moreover, a rabbit anti-recombinant BgHSP90 antibody was developed, and the protein synthesis of BgHSP90 in the DA-resistant isolate was compared with that in the wild-type by Western blot analysis and indirect fluorescence assay. There was significantly less BgHSP90 protein than in the wild-type. Additionally, the relative intensity of BgHSP70 in DA-resistant isolate was also lower than that in the wild-type. This suggested that the expression of BgHSP90 and BgHSP70 in the DA-resistant B. gibsoni isolate was suppressed and that the reduced amount of BgHSP90 and BgHSP70 might cause the weak proliferation of the DA-resistant isolate. Further studies are necessary to elucidate the function of BgHSP90.
• Echocardiographic estimation of left ventricular-arterial coupling in dogs with myxomatous mitral valve disease.

  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 [査読有り]
   

  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.
• Acute effects of intravenous pimobendan administration in dog models of chronic precapillary pulmonary hypertension

  T. Morita, K. Nakamura, T. Osuga, S. Kawamoto, S. Miki, K. Sasaoka, M. Takiguchi

  Journal of Veterinary Cardiology 32 16 - 27 2020年12月 

  © 2020 Elsevier B.V. Introduction: Pulmonary hypertension (PH) is a progressive and potentially life-threatening disease. Several drugs are used for the treatment of dogs with precapillary PH. Pimobendan is an inotropic drug with phosphodiesterase 3 inhibitory and calcium-sensitizing effects. Pimobendan administration improved right ventricular (RV) function and lowered pulmonary arterial pressure in some human patients with precapillary PH. However, the efficacy of pimobendan in dogs with precapillary PH is unknown. Animals, material, and methods: An implantable port device was percutaneously placed in the cranial vena cava of five laboratory beagles. Chronic embolic precapillary PH was induced via the repeated injection of microspheres every 1–2 days. Microsphere injection was continued until systolic pulmonary arterial pressure reached 50 mmHg. Right heart catheterization and echocardiography were performed at baseline and after injections of placebo and pimobendan (0.15 mg/kg). Results: Repeated injections of microspheres caused an increase in pulmonary vascular resistance, a decrease in stroke volume, RV dilation, left ventricular (LV) and RV dysfunction, and RV dyssynchrony as assessed using echocardiography. Compared with placebo, pimobendan improved LV and RV function based on the LV Tei index from 0.48 to 0.38 (p=0.002) and the RV Tei index from 0.76 to 0.61 (p=0.008), as well as the stroke volume index from 29.4 to 36.7 ml/m2 (p=0.012), respectively. Conclusions: In dog models of chronic PH, intravenous pimobendan effectively improved RV and LV function and increased stroke volume. However, pimobendan administration did not decrease pulmonary arterial pressure or produce hypotension.
• Long interspersed nucleotide element-1 hypomethylation in canine malignant mucosal melanoma.

  Teita Ishizaki, Jumpei Yamazaki, Shinji Meagawa, Nozomu Yokoyama, Keisuke Aoshima, Mitsuyoshi Takiguchi, Takashi Kimura

  Veterinary and comparative oncology 18 4 854 - 860 2020年12月 [査読有り]
   

  Canine malignant melanoma is a common cancer with a high mortality rate and is a clinically important disease. DNA methylation has been considered to be a potential tumorigenic mechanism through aberrant DNA methylation at promoter region which represses gene transcription. Global hypomethylation could also facilitate chromosome instability. There are few reports regarding DNA methylation in canine malignant melanoma; therefore, the purpose of this study was to examine DNA methylation status of long interspersed nucleotide element-1 (LINE-1) to be a surrogate marker of genome-wide methylation changes in this disease. We measured levels of DNA methylation of two adjacent cytosine-guanine sites on CpG island (CGI) at the putative promoter of canine LINE-1 sequence by bisulphite-pyrosequencing in 41 canine melanoma patient samples as well as six cell lines compared with normal mucosae. The survival rates were obtained from owners or medical records. We found DNA methylation levels of LINE-1 in normal mucosae were methylated. Interestingly, both melanoma cell lines and clinical melanoma samples showed remarkable hypomethylation. In addition, patients with lower LINE-1 methylation showed worse prognosis than those with higher LINE-1 methylation, though the difference did not reach statistical significance (P = .09). Here, we demonstrate that hypomethylation of LINE-1 is an epigenetically aberrant feature in canine melanoma with possible prognostic value.
• Wobbly hedgehog syndrome with disseminated histiocytic sarcoma and lateral ventricular meningioma in an African pygmy hedgehog.

  Lesa A Thompson, Atsuya Morita, Shoko Murakami, Noboru Sasaki, Miou Murashita, Ryou Yamazaki, Atsushi Kobayashi, Takashi Kimura, Mitsuyoshi Takiguchi

  Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc 32 6 953 - 956 2020年11月 [査読有り]
   

  An 8-mo-old male African pygmy hedgehog was anorectic and ataxic; physical examination revealed tetraparesis and a gangrenous left hindlimb. Analgesic and supportive care were administered, but the animal died 3 d after presentation. Postmortem examination revealed a histiocytic sarcoma in a mesenteric lymph node with metastasis to several organs, multifocal vacuolation in the cerebral and cerebellar white matter, and a meningioma in the left lateral ventricle. We diagnosed wobbly hedgehog syndrome (WHS) with disseminated histiocytic sarcoma and lateral ventricular meningioma. Ventricular meningioma, a rare neoplasm in veterinary and human patients, has not been reported previously in hedgehogs, to our knowledge. The neurologic signs in our case were probably caused by the WHS-related vacuolar lesions and are consistent with those of reported WHS cases. Duration of illness was shorter than is typical of WHS cases, which might be related to the disseminated histiocytic sarcoma. Clinical relevance of the lateral ventricular meningioma was not evident because the ventricular mass was localized and not invasive.
• Gene expression of leucine-rich alpha-2 glycoprotein in the polypoid lesion of inflammatory colorectal polyps in miniature dachshunds.

  Hiroshi Ohta, Yu Tamura, Nozomu Yokoyama, Noriyuki Nagata, Tatsuyuki Osuga, Noboru Sasaki, Yumiko Kagawa, Keitaro Morishita, Mitsuyoshi Takiguchi

  The Journal of veterinary medical science 82 10 1445 - 1449 2020年10月20日 [査読有り]
   

  Inflammatory colorectal polyps (ICRPs) in miniature dachshunds (MDs) are speculated to be a breed-specific inflammatory bowel disease (IBD). Leucine-rich alpha-2 glycoprotein (LRG) has been identified as a novel biomarker of human IBD. The aim of this study was to examine LRG gene expression in the polypoid lesions of ICRPs. Polypoid lesion specimens were collected from 24 MDs with ICRPs. Nonpolypoid colonic mucosa was collected from 18 MDs with ICRPs and 10 controls. The gene expression of LRG, interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and IL-22 was examined. The expression of LRG gene was significantly increased in the polypoid lesions of ICRPs and correlated with that of the four cytokines. In conclusion, the LRG gene was expressed within the polypoid lesions of ICRPs and might be associated with local cytokine expression.
• Altered hepatic cytochrome P450 expression in cats after chronic exposure to decabromodiphenyl ether (BDE-209).

  Kraisiri Khidkhan, Hazuki Mizukawa, Yoshinori Ikenaka, Shouta M M Nakayama, Kei Nomiyama, Nozomu Yokoyama, Osamu Ichii, Mitsuyoshi Takiguchi, Shinsuke Tanabe, Mayumi Ishizuka

  The Journal of veterinary medical science 82 7 978 - 982 2020年07月31日 [査読有り]
   

  The knowledge of cytochrome P450 (CYP) expression involved in chemical exposure are necessary in clinical applications for the medication and prediction of adverse effects. The aim of this study was to evaluate the mRNA expression of CYP1-CYP3 families in cats exposed to BDE-209 for one year. All selected CYP isoforms showed no significant difference in mRNA expressions between control and exposure groups, however, CYP3A12 and CYP3A131 revealed tend to be two times higher in the exposure group compared to control group. The present results indicate that the chronic exposure of BDE209 could not alter CYP expression in the liver of cats. This result considered caused by the deficiency of CYP2B subfamily which is major metabolism enzyme of polybrominated diphenyl ethers (PBDEs) in cat.
• An area ratio of thyroid gland to common carotid artery for evaluating the thyroid gland size.

  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.
• Activities of matrix metalloproteinase-2, matrix metalloproteinase-9, and serine proteases in samples of the colorectal mucosa of Miniature Dachshunds with inflammatory colorectal polyps.

  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.
• Wobbly hedgehog syndrome with disseminated histiocytic sarcoma and lateral ventricular meningioma in an African pygmy hedgehog

  Lesa A. Thompson, Atsuya Morita, Shoko Murakami, Noboru Sasaki, Miou Murashita, Ryou Yamazaki, Atsushi Kobayashi, Takashi Kimura, Mitsuyoshi Takiguchi

  J Vet Diagn Invest 2020年06月 [査読有り][通常論文]
  
• Altered hepatic cytochrome P450 expression in cats after chronic exposure to decabromodiphenyl ether (BDE-209).

  Kraisiri Khidkhan, Hazuki Mizukawa, Yoshinori Ikenaka, Shouta M M Nakayama, Kei Nomiyama, Nozomu Yokoyama, Osamu Ichii, Mitsuyoshi Takiguchi, Shinsuke Tanabe, Mayumi Ishizuka

  The Journal of veterinary medical science 82 7 978 - 982 2020年05月21日 [査読有り][通常論文]
   

  The knowledge of cytochrome P450 (CYP) expression involved in chemical exposure are necessary in clinical applications for the medication and prediction of adverse effects. The aim of this study was to evaluate the mRNA expression of CYP1-CYP3 families in cats exposed to BDE-209 for one year. All selected CYP isoforms showed no significant difference in mRNA expressions between control and exposure groups, however, CYP3A12 and CYP3A131 revealed tend to be two times higher in the exposure group compared to control group. The present results indicate that the chronic exposure of BDE209 could not alter CYP expression in the liver of cats. This result considered caused by the deficiency of CYP2B subfamily which is major metabolism enzyme of polybrominated diphenyl ethers (PBDEs) in cat.
• Genome-wide DNA methylation analysis in canine gastrointestinal lymphoma.

  Hiroshi Ohta, Jumpei Yamazaki, Jaroslav Jelinek, Teita Ishizaki, Yumiko Kagawa, Nozomu Yokoyama, Noriyuki Nagata, Noboru Sasaki, Mitsuyoshi Takiguchi

  The Journal of veterinary medical science 82 5 632 - 638 2020年03月25日 [査読有り][通常論文]
   

  DNA methylation is the covalent modification of methyl groups to DNA mostly at CpG dinucleotides and one of the most studied epigenetic mechanisms that leads to gene expression variability without affecting the DNA sequence. Genome-wide analysis of DNA methylation identified the signatures that could define subtypes of human lymphoma patients. The objective of this study was to conduct the genome-wide analysis of DNA methylation in dogs with gastrointestinal lymphoma (GIL). Genomic DNA was extracted from endoscopic biopsies from 10 dogs with GIL. We performed Digital Restriction Enzyme Assay of DNA Methylation (DREAM) for genome-wide DNA methylation analysis that could provide highly quantitative information on DNA methylation levels of CpG sites across the dog genome. We successfully obtained data of quantitative DNA methylation level for 148,601-162,364 CpG sites per GIL sample. Next, we analyzed 83,132 CpG sites to dissect the differences in DNA methylation between GIL and normal peripheral blood mononuclear cells (PBMCs). We found 383-3,054 CpG sites that were hypermethylated in GIL cases compared to PBMCs. Interestingly, 773 CpG sites including promoter regions of 61 genes were identified to be commonly hypermethylated in more than half of the cases, suggesting conserved DNA methylation patterns that are abnormal in GIL. This study revealed that there was a large number of hypermethylated sites that are common in most of canine GIL. These abnormal DNA methylation could be involved in tumorigenesis of the canine GIL.
• Long interspersed nucleotide element-1 hypomethylation in canine malignant mucosal melanoma.

  Teita Ishizaki, Jumpei Yamazaki, Shinji Meagawa, Nozomu Yokoyama, Keisuke Aoshima, Mitsuyoshi Takiguchi, Takashi Kimura

  Veterinary and comparative oncology 18 4 854 - 860 2020年03月18日 [査読有り][通常論文]
   

  Canine malignant melanoma is a common cancer with a high mortality rate and is a clinically important disease. DNA methylation has been considered to be a potential tumorigenic mechanism through aberrant DNA methylation at promoter region which represses gene transcription. Global hypomethylation could also facilitate chromosome instability. There are few reports regarding DNA methylation in canine malignant melanoma; therefore, the purpose of this study was to examine DNA methylation status of long interspersed nucleotide element-1 (LINE-1) to be a surrogate marker of genome-wide methylation changes in this disease. We measured levels of DNA methylation of two adjacent cytosine-guanine sites on CpG island (CGI) at the putative promoter of canine LINE-1 sequence by bisulphite-pyrosequencing in 41 canine melanoma patient samples as well as six cell lines compared with normal mucosae. The survival rates were obtained from owners or medical records. We found DNA methylation levels of LINE-1 in normal mucosae were methylated. Interestingly, both melanoma cell lines and clinical melanoma samples showed remarkable hypomethylation. In addition, patients with lower LINE-1 methylation showed worse prognosis than those with higher LINE-1 methylation, though the difference did not reach statistical significance (P = .09). Here, we demonstrate that hypomethylation of LINE-1 is an epigenetically aberrant feature in canine melanoma with possible prognostic value.
• Clinical characteristics of dogs with food-responsive protein-losing enteropathy.

  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.
• Computed tomographic features for differentiating benign from malignant liver lesions in dogs.

  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]
   

  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.
• Tissue distribution and characterization of feline cytochrome P450 genes related to polychlorinated biphenyl exposure.

  Khidkhan K, Mizukawa H, Ikenaka Y, Nakayama SMM, Nomiyama K, Yokoyama N, Ichii O, Darwish WS, Takiguchi M, Tanabe S, Ishizuka M

  Comparative biochemistry and physiology. Toxicology & pharmacology : CBP 226 108613 - 108613 2019年12月 [査読有り][通常論文]
   

  Cats have been known to be extremely sensitive to chemical exposures. To understand these model species' sensitivity to chemicals and their toxicities, the expression profiles of xenobiotic-metabolizing enzymes should be studied. Unfortunately, the characterization of cytochrome P450 (CYP), the dominant enzyme in phase I metabolism, in cats has not extensively been studied. Polychlorinated biphenyls (PCBs) are known as CYP inducers in animals, but the information regarding the PCB-induced CYP expression in cats is limited. Therefore, in the present study, we aimed to elucidate the mRNA expression of the CYP1–CYP3 families in the cat tissues and to investigate the CYP mRNA expression related to PCB exposure. In cats, the greatest abundance of CYP1–CYP3 (CYP1A2, CYP2A13, CYP2C41, CYP2D6, CYP2E1, CYP2E2, CYP2F2, CYP2F5, CYP2J2, CYP2U1, and CYP3A132) was expressed in the liver, but some extrahepatic isozymes were found in the kidney (CYP1A1), heart (CYP1B1), lung (CYP2B11 and CYP2S1) and small intestine (CYP3A131). In cats, CYP1A1, CYP1A2 and CYP1B1 were significantly upregulated in the liver as well as in several tissues exposed to PCBs, indicating that these CYPs were distinctly induced by PCBs. The strong correlations between 3,3′,4,4′-tetrachlorobiphenyl (CB77) and CYP1A1 and CYP1B1 mRNA expressions were noted, demonstrating that CB77 could be a potent CYP1 inducer. In addition, these CYP isoforms could play an essential role in the PCBs biotransformation, particularly 3–4 Cl-PCBs, because a high hydroxylated metabolite level of 3–4 Cl-OH-PCBs was observed in the liver.
• Computed tomographic features for differentiating benign from malignant liver lesions in dogs.

  Leela-Arporn R, Ohta H, Shimbo G, Hanazono K, Osuga T, Morishita K, Sasaki N, Takiguchi M

  The Journal of veterinary medical science 81 12 1697 - 1704 2019年12月 [査読有り][通常論文]
  
• Effects of PCB exposure on serum thyroid hormone levels in dogs and cats.

  Takaguchi K, Nishikawa H, Mizukawa H, Tanoue R, Yokoyama N, Ichii O, Takiguchi M, Nakayama SMM, Ikenaka Y, Kunisue T, Ishizuka M, Tanabe S, Iwata H, Nomiyama K

  The Science of the total environment 688 1172 - 1183 2019年10月 [査読有り][通常論文]
   

  Polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (OH-PCBs) might disrupt thyroid function. However, there is no clear evidence of PCB exposure disrupting thyroid hormone (TH) homeostasis in dogs and cats. The present study conducted in vivo experiments to evaluate the effects of a mixture of 12 PCB congeners (CB18, 28, 70, 77, 99, 101, 118, 138, 153, 180, 187 and 202, each congener 0.5 mg/kg BW, i.p. administration) on serum TH levels in male dogs (Canis lupus familiaris) and male cats (Felis silvestris catus). In PCB-exposed dogs, the time courses of higher-chlorinated PCBs and L-thyroxine (T4)-like OH-PCBs (4-OH-CB107 and 4-OH-CB202) concentrations were unchanged or tended to increase, whereas those of lower-chlorinated PCBs and OH-PCBs tended to decrease after 24 h. In PCB-exposed cats, concentrations of PCBs increased until 6 h and then remained unchanged. The levels of lower-chlorinated OH-PCBs including 4'-OH-CB18 increased until 96 h and then decreased. In PCB-exposed dogs, free T4 concentrations were higher than those in the control group at 48 and 96 h after PCB administration and positively correlated with the levels of T4-like OH-PCBs, suggesting competitive binding of T4 and T4-like OH-PCBs to a TH transporter, transthyretin. Serum levels of total T4 and total 3,3',5-triiodo-L-thyronine (T3) in PCB-exposed dogs were lower than in the control group at 24 and 48 h and negatively correlated with PCB concentrations, implying that PCB exposure enhanced TH excretion by increasing TH uptake and TH conjugation enzyme activities in the dog liver. In contrast, no obvious changes in TH levels were observed in PCB-exposed cats. This could be explained by the lower levels of T4-like OH-PCBs and lower hepatic conjugation enzyme activities in cats compared with dogs. Different effects on serum TH levels in PCB-exposed dogs and cats are likely to be attributable to species-specific PCB and TH metabolism.
• Change in right ventricular function in an American cocker spaniel with acute pulmonary thromboembolism.

  Morita T, Nakamura K, Osuga T, Hanazono K, Morishita K, Takiguchi M

  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.
• Usefulness of noninvasive shear wave elastography for the assessment of hepatic fibrosis in dogs with hepatic disease.

  Tamura M, Ohta H, Shimbo G, Osuga T, Sasaki N, Morishita K, Kagawa Y, Takiguchi M

  Journal of veterinary internal medicine 33 5 2067 - 2074 2019年09月 [査読有り][通常論文]
  
• Effect of ultra low fat diet on regulatory T cells of dogs with intestinal limphangiectasia secondary to chronic enteropathy: A pilot study

  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.
• Findings of contrast-enhanced ultrasonography with Sonazoid for cholangiocellular adenoma in three dogs.

  Tamura M, Nakamura K, Osuga T, Shimbo G, Sasaki N, Morishita K, Ohta H, Takiguchi M

  The Journal of veterinary medical science 81 8 1104 - 1108 2019年08月 [査読有り][通常論文]
  
• Plasma amino acid profiles in dogs with inflammatory bowel disease.

  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 

  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.
• Plasma-free amino acid profiles in dogs with hepatocellular carcinoma.

  Leela-Arporn R, Ohta H, Tamura M, Nagata N, Sasaoka K, Dermlim A, Nisa K, Osuga T, Morishita K, Sasaki N, Takiguchi M

  Journal of veterinary internal medicine 33 4 1653 - 1659 2019年07月 [査読有り][通常論文]
  
• Effect of acute volume loading on left atrial strain values derived from two-dimensional speckle tracking echocardiography in dogs.

  Dermlim A, Osuga T, Nakamura K, Morita T, Nisa K, Sasaoka K, Leela-Arporn R, Nagata N, Tamura M, Sasaki N, Ohta H, Takiguchi M

  The Journal of veterinary medical science 81 7 949 - 957 2019年07月 [査読有り][通常論文]
  
• Epidemiology of massive hepatocellular carcinoma in dogs: A 4-year retrospective study.

  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]
  
• Right ventricular function and dyssynchrony measured by echocardiography in dogs with precapillary pulmonary hypertension

  T. Morita, K. Nakamura, T. Osuga, K. Morishita, N. Sasaki, H. Ohta, M. Takiguchi

  Journal of Veterinary Cardiology 23 1 - 14 Elsevier {BV} 2019年06月 [査読有り][通常論文]
  
• The repeatability and left atrial strain analysis obtained via speckle tracking echocardiography in healthy dogs.

  Dermlim, A, Nakamura, K, Morita, T, Osuga, T, Nisa, K, Sasaoka, K, Leela-arporn, R, Sasaki, N, Ohta, H, Takiguchi, M

  Journal of Veterinary Cardiology 23 1 69 - 80 2019年06月 [査読有り][通常論文]
  
• Predictive factors of malignancy in dogs with focal liver lesions using clinical data and ultrasonographic features.

  Leela-Arporn R, Ohta H, Tamura M, Nagata N, Sasaoka K, Dermlim A, Nisa K, Morishita K, Sasaki N, Nakamura K, Takagi S, Hosoya K, Takiguchi M

  The Journal of veterinary medical science 81 5 723 - 729 2019年05月 [査読有り][通常論文]
  
• Plasma amino acid profiles in dogs with inflammatory bowel disease.

  Tamura Y, Ohta H, Kagawa Y, Osuga T, Morishita K, Sasaki N, Takiguchi M

  Journal of veterinary internal medicine 2019年05月 [査読有り][通常論文]
  
• Evaluation of liver and spleen stiffness of healthy dogs by use of two-dimensional shear wave elastography.

  Tamura M, Ohta H, Nisa K, Osuga T, Sasaki N, Morishita K, Takiguchi M

  American journal of veterinary research 80 4 378 - 384 2019年04月 [査読有り][通常論文]
  
• Evaluation of duodenal perfusion by contrast-enhanced ultrasonography in dogs with chronic inflammatory enteropathy and intestinal lymphoma.

  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.
• Contrast-enhanced ultrasonography is a feasible technique for quantifying hepatic microvascular perfusion in dogs with extrahepatic congenital portosystemic shunts.

  Tamura M, Ohta H, Nisa K, Osuga T, Sasaki N, Morishita K, Takiguchi M

  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]
  
• Evaluation of duodenal perfusion by contrast-enhanced ultrasonography in dogs with chronic inflammatory enteropathy and intestinal lymphoma.

  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.
• Low-intensity pulsed ultrasound modifies effects of a myelin-related growth inhibitor and enhances neurite re-growth

  Noboru Sasaki, Nobuki Kudo, Hiroshi Ohta, Mitsuyoshi Takiguchi

  2019 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IUS) 1308 - 1310 2019年 

  Axon regeneration is crucial for the functional recovery after spinal cord injury. Myelin-related growth inhibitors, such as Nogo-A, inhibit neurites regrowth and elongation. Low-intensity pulsed ultrasound (LIPUS) is known to show neuroprotective effects in neurodegenerative diseases. In the present study, we evaluated the feasibility of LIPUS for enhancing axon regeneration in the presence of Nogo-A. Low-intensity pulsed ultrasound was exposed to rat cortical neurons in vitro after Nogo-A treatment. The total length of neurites per cell in LIPUS group was significantly larger than that of non-LIPUS group. There was no significant difference in the number of neurites. The results suggest that LIPUS may enhance the elongation of neurites in the presence of Nogo-A while may not affect on neurites sprouting and branching. This preliminary study implies the feasibility of LIPUS for axonal regeneration.
• Corrigendum: Urinary Exosome-Derived microRNAs Reflecting the Changes in Renal Function in Cats.

  Ichii O, Ohta H, Horino T, Nakamura T, Hosotani M, Mizoguchi T, Morishita K, Nakamura K, Sasaki N, Takiguchi M, Sato R, Oyamada K, Elewa YHA, Kon Y

  Frontiers in veterinary science 6 2  2019年 [査読有り][通常論文]
  
• Effect of acute volume overload on echocardiographic indices of right ventricular function and dyssynchrony assessed by use of speckle tracking echocardiography in healthy dogs.

  Morita T, Nakamura K, Osuga T, Yokoyama N, Morishita K, Sasaki N, Ohta H, Takiguchi M

  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.
• Effects of immunosuppressive prednisolone therapy on pancreatic tissue and concentration of canine pancreatic lipase immunoreactivity in healthy dogs.

  Ohta H, Kojima K, Yokoyama N, Sasaki N, Kagawa Y, Hanazono K, Ishizuka T, Morishita K, Nakamura K, Takagi S, Takiguchi M

  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 mu g/L) in 5 dogs and as abnormal (>= 400 mu g/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 mu g/L) was observed in only 1 dog. No ultrasonographic or histological evidence of pancreatitis was observed in any of the dogs.
• ECG of the Month.

  Osuga T, Nakamura K, Morita T, Watanabe K, Takiguchi M

  Journal of the American Veterinary Medical Association 253 4 417 - 420 2018年08月 [査読有り][通常論文]
  
• Pulmonary hypertension due to unclassified interstitial lung disease in a Pembroke Welsh corgi.

  Morita T, Nakamura K, Osuga T, Kobayashi A, Ichii O, Yabuki A, Takiguchi M

  The Journal of veterinary medical science 80 6 939 - 944 2018年06月 [査読有り][通常論文]
  
• The effect of sedation with a combination of butorphanol and midazolam on quantitative contrast-enhanced ultrasonography of duodenum in healthy dogs.

  Nisa K, Lim SY, 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

  The Journal of Veterinary Medical Science 80 3 453 - 459 2018年03月 [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.
• The effect of sedation with a combination of butorphanol and midazolam on quantitative contrast-enhanced ultrasonography of duodenum in healthy dogs

  Nisa K, Lim S.Y, 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 Medical Science 80 3 453 - 459 2018年03月 [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.
• Urinary Exosome-Derived microRNAs Reflecting the Changes in Renal Function in Cats.

  Ichii O, Ohta H, Horino T, Nakamura T, Hosotani M, Mizoguchi T, Morishita K, Nakamura K, Sasaki N, Takiguchi M, Sato R, Oyamada K, Elewa YHA, Kon Y

  Frontiers in veterinary science 5 289  2018年 [査読有り][通常論文]
  
• Transcranial Doppler Ultrasound Examination in Dogs with Suspected Intracranial Hypertension Caused by Neurologic Diseases

  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.
• Intracellular diminazene aceturate content and adenosine incorporation in diminazene aceturate-resistant Babesia gibsoni isolate in vitro.

  Yamasaki M, Watanabe N, Idaka N, Yamamori T, Otsuguro KI, Uchida N, Iguchi A, Ohta H, Takiguchi M

  Experimental parasitology 183 92 - 98 2017年12月 [査読有り][通常論文]
   

  The mechanism of the development of diminazene aceturate (DA) resistance in Babesia gibsoni is still unknown even though DA-resistant B. gibsoni isolate was previously developed in vitro. To clarify the mechanisms of DA-resistance in B. gibsoni, we initially examined the intracellular DA content in the DA resistant isolate using high-performance liquid chromatography, and compared it with that in the wild type. As a result, the intracellular DA content in the DA-resistant isolate was significantly lower than that in the wild-type, suggesting that the decreased DA content may contribute to DA-resistance. Additionally, the glucose consumption of the DA-resistant isolate was significantly higher than that of the wild-type, indicating that a large amount of glucose is utilized to maintain DA-resistance. It is possible that a large amount of energy is utilized to maintain the mechanisms of DA-resistance. It was reported that as the structure of DA is similar with that of adenosine, DA may be taken up by the P2 transporter, which contributes to the uptake of adenosine, in Trypanosoma brucei brucei, and that the uptake of adenosine is decreased in DA-resistant T brucei brucei. In the present study, the adenosine incorporation in the DA-resistant B. gibsoni isolate was higher than in the wild-type. Moreover, the adenosine incorporation in the wild-type was not inhibited by the presence of DA. These results suggest that adenosine transport in B. gibsoni is not affected by DA and may not mediate DA-resistance. To clarify the mechanism of the development of DA resistance in B. gibsoni, we should investigate the cause of the decreased DA content in the DA-resistant isolate in the future. (C) 2017 Elsevier Inc. All rights reserved.
• Case report: Congenital methemoglobinemia in a cat with the reduced NADH-cytochrome b5 reductase 3 activity and missense mutations in CYB5R3

  Akiyoshi Tani, Jumpei Yamazaki, Kensuke Nakamura, Mitsuyoshi Takiguchi, Mutsumi Inaba

  Japanese Journal of Veterinary Research 65 4 201 - 206 Faculty of Veterinary Medicine, Hokkaido University 2017年11月 [査読有り][通常論文]
   

  © 2017, Hokkaido University. All rights reserved. A one-year-old castrated male mixed-breed cat was referred for detailed examination of long-term pale mucous membrane without any clinical episodes that may cause cyanosis. While no causative abnormalities were detected in thoracic radiography and echocardiography, and arterial partial pressure of oxygen was within normal value, methemoglobin concentration of the cat was increased to 30% and cytochrome b5 reductase activity, which converts methemoglobin to hemoglobin, was reduced to 2.0 IU/gHb (13.4 ± 1.7 IU/gHb in control cats, n = 3), indicating congenital methemoglobinemia. Sequence analysis of CYB5R3, which codes cytochrome b5 reductase, showed two missense mutations found in the patient, one of which was predicted to affect protein function.
• Spatial and temporal profile of cisplatin delivery by ultrasound-assisted intravesical chemotherapy in a bladder cancer model

  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.
• Diastolic heart failure associated with hemangiosarcoma infiltrating left ventricular walls in a dog

  Osuga T, Nakamura K, Morita T, Kagawa Y, Ohta H, Takiguchi M

  Canadian Veterinary Journal 58 11 1167 - 1170 2017年11月 [査読有り][通常論文]
  
• Repeatability and reproducibility of quantitative contrast-enhanced ultrasonography for assessing duodenal perfusion in healthy dogs.

  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]
   

  Contrast-enhanced ultrasonography (CEUS) with microbubbles as a contrast agent allows the visualization and quantification of tissue perfusion. The assessment of canine intestinal perfusion by quantitative CEUS may provide valuable information for diagnosing and monitoring chronic intestinal disorders. This study aimed to assess the repeatability (intraday variability) and reproducibility (interday variability) of quantitative duodenal CEUS in healthy dogs. Six healthy beagles underwent CEUS three times within one day (4-hr intervals) and on two different days (1-week interval). All dogs were sedated with a combination of butorphanol (0.2 mg/kg) and midazolam (0.1 mg/kg) prior to CEUS. The contrast agent (Sonazoid®) was administered using the intravenous bolus method (0.01 ml/kg) for imaging of the duodenum. Time-intensity curves (TIC) were created by drawing multiple regions of interest (ROIs) in the duodenal mucosa, and perfusion parameters, including the time-to-peak (TTP), peak intensity (PI), area under the curve (AUC), and wash-in and wash-out rates (WiR and WoR, respectively), were generated. Intraday and interday coefficients of variation (CVs) for TTP, PI, AUC, WiR and WoR were <25% (range, 2.27-23.41%), which indicated that CEUS was feasible for assessing duodenal perfusion in healthy sedated dogs. A further study of CEUS in dogs with chronic intestinal disorders is necessary to evaluate its clinical applicability.
• Repeatability and reproducibility of quantitative contrast-enhanced ultrasonography for assessing duodenal perfusion in healthy dogs

  Nisa K, Lim S.Y, 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

  Journal of Veterinary Medical Science 79 9 1585 - 1590 2017年09月 [査読有り][通常論文]
   

  Contrast-enhanced ultrasonography (CEUS) with microbubbles as a contrast agent allows the visualization and quantification of tissue perfusion. The assessment of canine intestinal perfusion by quantitative CEUS may provide valuable information for diagnosing and monitoring chronic intestinal disorders. This study aimed to assess the repeatability (intraday variability) and reproducibility (interday variability) of quantitative duodenal CEUS in healthy dogs. Six healthy beagles underwent CEUS three times within one day (4-hr intervals) and on two different days (1-week interval). All dogs were sedated with a combination of butorphanol (0.2 mg/kg) and midazolam (0.1 mg/kg) prior to CEUS. The contrast agent (Sonazoid®) was administered using the intravenous bolus method (0.01 ml/kg) for imaging of the duodenum. Time-intensity curves (TIC) were created by drawing multiple regions of interest (ROIs) in the duodenal mucosa, and perfusion parameters, including the time-to-peak (TTP), peak intensity (PI), area under the curve (AUC), and wash-in and wash-out rates (WiR and WoR, respectively), were generated. Intraday and interday coefficients of variation (CVs) for TTP, PI, AUC, WiR and WoR were <25% (range, 2.27-23.41%), which indicated that CEUS was feasible for assessing duodenal perfusion in healthy sedated dogs. A further study of CEUS in dogs with chronic intestinal disorders is necessary to evaluate its clinical applicability.
• Brain micro-inflammation at specific vessels dysregulates organ-homeostasis via the activation of a new neural circuit

  Yasunobu Arima, Takuto Ohki, Naoki Nishikawa, Kotaro Higuchi, Mitsutoshi Ota, Yuki Tanaka, Junko Nio-Kobayashi, Mohamed Elfeky, Ryota Sakai, Yuki Mori, Tadafumi Kawamoto, Andrea Stofkova, Yukihiro Sakashita, Yuji Morimoto, Masaki Kuwatani, Toshihihiko Iwanaga, Yoshichika Yoshioka, Naoya Sakamoto, Akihiko Yoshimura, Mitsuyoshi Takiguchi, Saburo Sakoda, Marco Prinz, Daisuke Kamimura, Masaaki Murakami

  ELIFE 6 2017年08月 [査読有り][通常論文]
   

  Impact of stress on diseases including gastrointestinal failure is well-known, but molecular mechanism is not understood. Here we show underlying molecular mechanism using EAE mice. Under stress conditions, EAE caused severe gastrointestinal failure with high-mortality. Mechanistically, autoreactive-pathogenic CD4+ T cells accumulated at specific vessels of boundary area of third-ventricle, thalamus, and dentate-gyrus to establish brain micro-inflammation via stress gateway reflex. Importantly, induction of brain micro-inflammation at specific vessels by cytokine injection was sufficient to establish fatal gastrointestinal failure. Resulting micro-inflammation activated new neural pathway including neurons in paraventricular-nucleus, dorsomedial-nucleus-ofhypothalamus, and also vagal neurons to cause fatal gastrointestinal failure. Suppression of the brain micro-inflammation or blockage of these neural pathways inhibited the gastrointestinal failure. These results demonstrate direct link between brain micro-inflammation and fatal gastrointestinal disease via establishment of a new neural pathway under stress. They further suggest that brain micro-inflammation around specific vessels could be switch to activate new neural pathway(s) to regulate organ homeostasis.
• Changes in right ventricular function assessed by echocardiography in dog models of mild RV pressure overload

  Morita T, Nakamura K, Osuga T, Yokoyama N, Morishita K, Sasaki N, Ohta H, Takiguchi M

  Echocardiography 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 A2 analog (U46619) (n=7). The mean PAP was mildly increased (19.3±1.1 mm 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, β=-0.60, P<.001; RV-SD, β=0.40, P=.011), pulmonary vascular resistance (free wall RVLS, β=-0.39, P=.020; RV-SD, β=0.47, P=.0086; Tei index, β=0.34, P=.047), and cardiac index (Tei index, β=-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.
• Stimulation of colorectal biopsies from miniature dachshunds with inflammatory colorectal polyps with toll-like receptor ligands: A pilot study

  Yokoyama N, Ohta H, Kagawa Y, Nagata N, Nisa K, Morita T, Osuga T, Sasaki N, Morishita K, Nakamura K, Takiguchi M

  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-1β, IL-6, IL-8 and TNF-α) gene expression in ex vivo-cultured colorectal samples from four MDs with ICRPs and four healthy MDs. At baseline, no significant difference in the mRNA expression levels of TLRs and pro-inflammatory cytokines was observed between cases and control MDs. After 4-h incubation, the relative ratios of TNF-α mRNA expression in the TLR2- or TLR4-stimulated colorectal samples, and IL-1β mRNA expression in the TLR9-stimulated colorectal samples form cases showed higher tendency compared with healthy MDs (P<0.05), although statistically not significant. The results of this pilot study using small number of cases indicated that reactivity against TLR2, TLR4 or TLR9 ligand in the production of pro-inflammatory cytokines might be enhanced in the colorectal mucosa of ICRPs. Further research is needed to perform the functional analysis of TLRs in the sole cell population using intestinal epithelial primary culture and the mononuclear cells isolated from colonic mucosa.
• Washout Ratio in the Hepatic Vein Measured by Contrast-Enhanced Ultrasonography to Distinguish Between Inflammatory and Noninflammatory Hepatic Disorders in Dogs

  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.
• Washout Ratio in the Hepatic Vein Measured by Contrast-Enhanced Ultrasonography to Distinguish Between Inflammatory and Noninflammatory Hepatic Disorders in Dogs.

  Morishita K, Hiramoto A, Michishita A, Takagi S, Osuga T, Lim SY, Nakamura K, Sasaki N, Ohta H, Takiguchi M

  Journal of veterinary internal medicine 31 3 770 - 777 2017年05月 [査読有り][通常論文]
  
• Assessment of contrast-enhanced ultrasonography of the hepatic vein for detection of hemodynamic changes associated with experimentally induced portal hypertension in dogs

  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.
• Expression of apical junction complex proteins in colorectal mucosa of miniature dachshunds with inflammatory colorectal polyps

  Yokoyama N, Ohta H, Kagawa Y, Leela-Arporn R, Dermlim A, Nisa K, Morita T, Osuga T, Sasaki N, Morishita K, Nakamura K, Takiguchi M

  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 β-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 β-catenin were not significantly different between control dogs and non-inflamed colonic mucosa from MDs with ICRPs. In contrast, only E-cadherin and β-catenin were detected in the inflamed lesions of MDs with ICRPs. By immunohistochemistry, claudin-2, -3, -4, -5 and -7, E-cadherin and β-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 β-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.
• Contrast-enhanced ultrasonography of the hepatic vein in normal dogs.

  Morishita K, Hiramoto A, Osuga T, Lim SY, Khoirun N, Sasaki N, Nakamura K, Ohta H, Yamasaki M, Takiguchi M

  The Journal of veterinary medical science 78 12 1753 - 1758 2017年01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® (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.
• Impact of surgical margins on survival of 37 dogs with massive hepatocellular carcinoma

  A. Matsuyama, S. Takagi, K. Hosoya, Y. Kagawa, K. Nakamura, T. Deguchi, M. Takiguchi

  NEW ZEALAND VETERINARY JOURNAL 65 5 227 - 231 2017年 [査読有り][通常論文]
   

  AIMS: To compare the survival of dogs with completely resected massive hepatocellular carcinoma (HCC) with that of dogs in which HCC were incompletely excised. METHODS: A retrospective cohort study was conducted. Dogs that underwent surgical excision of massive HCC between November 2006 and April 2015 were included. Dogs that died in the perioperative period or were lost to follow-up within 2 months after surgery were excluded. Data were collected from the medical records and a single pathologist examined all available histology slides to confirm the diagnosis of HCC. Surgical margins were defined as complete if no neoplastic cells were seen at the edge of excised tissues, based on original histopathology reports. Progression-free survival (PFS) and overall survival (OS) were compared between dogs with complete surgical margins (CM) and those with incomplete margins (IM) using a log-rank test. RESULTS: Of the 37 dogs included in the study, 25 were allocated to the CM group and 12 to the IM group. Progressive local disease developed after surgery in three dogs in the CM group and seven dogs in the IM group. Three dogs in the CM group and five dogs in the IM group died due to tumour progression. Median PFS was longer for dogs in the CM group (1,000 (95% CI=562-1,438) days) compared to dogs in the IM group (521 (95% CI=243-799) days; p=0.007). OS was also longer for dogs in the CM group (>1,836 days) compared to those in the IM group (median 765 (95% CI=474-1,056) days; p=0.02). CONCLUSIONS AND CLINICAL RELEVANCE: Compared with complete resection, incomplete resection decreased PFS and OS in dogs with massive HCC. Dogs with incompletely excised HCC should be closely monitored for local recurrence, although median OS was >2 years following incomplete excision. Further prospective studies are warranted to confirm these findings.
• Urinary exosome-derived microRNAs reflecting the changes of renal function and histopathology in dogs

  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.
• Serial measurement of pancreatic lipase immunoreactivity concentration in dogs with immune-mediated disease treated with prednisolone

  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.
• Localization of Toll-like Receptor (TLR) 2 and TLR4 mRNA in the Colorectal Mucosa of Miniature Dachshunds with Inflammatory Colorectal Polyps

  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.
• Left Atrial Strain at Different Stages of Myxomatous Mitral Valve Disease in Dogs

  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]
  
• The repeatability and characteristics of right ventricular longitudinal strain imaging by speckle-tracking echocardiography in healthy dogs

  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.
• Molecular cloning, phylogenetic analysis and heat shock response of Babesia gibsoni heat shock protein 90.

  Masahiro Yamasaki, Yoshihiro Tsuboi, Yusuke Taniyama, Naohiro Uchida, Reeko Sato, Kensuke Nakamura, Hiroshi Ohta, Mitsuyoshi Takiguchi

  The Journal of veterinary medical science 78 8 1355 - 60 2016年09月01日 [査読有り][通常論文]
   

  The Babesia gibsoni heat shock protein 90 (BgHSP90) gene was cloned and sequenced. The length of the gene was 2,610 bp with two introns. This gene was amplified from cDNA corresponding to full length coding sequence (CDS) with an open reading frame of 2,148 bp. A phylogenetic analysis of the CDS of HSP90 gene showed that B. gibsoni was most closely related to B. bovis and Babesia sp. BQ1/Lintan and lies within a phylogenetic cluster of protozoa. Moreover, mRNA transcription profile for BgHSP90 exposed to high temperature were examined by quantitative real-time reverse transcription-polymerase chain reaction. BgHSP90 levels were elevated when the parasites were incubated at 43°C for 1 hr.
• Effects of experimental cardiac volume loading on left atrial phasic function in healthy dogs

  Osuga T, Nakamura K, Morita T, Nisa K, Yokoyama N, Sasaki N, Morishita K, Ohta H, Takiguchi M

  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.
• Hypercalcemia in a Dog with Chronic Ingestion of Maxacalcitol Ointment.

  Nakamura K, Tohyama N, Yamasaki M, Ohta H, Morishita K, Takiguchi M

  Journal of the American Animal Hospital Association 52 4 256 - 258 2016年07月 [査読有り][通常論文]
  
• Repeatability and reproducibility of right ventricular Tei index valves derived from three echocardiographic methods for evaluation of cardiac function in dogs

  Morita T, Nakamura K, Osuga T, Lim S.Y, Yokoyama N, Morishita K, Ohta H, Takiguchi M

  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.
• Prognostic Value of Right Ventricular Tei Index in Dogs with Myxomatous Mitral Valvular Heart Disease

  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.
• Effects of various cardiovascular drugs on indices obtained with two-dimensional speckle tracking echocardiography of the left atrium and time-left atrial area curve analysis in healthy dogs

  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.
• Quantitative contrast-enhanced ultrasonographic assessment of naturally occurring pancreatitis in dogs.

  Lim SY, Nakamura K, Morishita K, Sasaki N, Murakami M, Osuga T, Yokoyama N, Ohta H, Yamasaki M, Takiguchi M

  Journal of veterinary internal medicine / American College 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.
• Vitamin D Status in Different Stages of Disease Severity in Dogs with Chronic Valvular Heart Disease

  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.
• CONTRAST-ENHANCED ULTRASONOGRAPHIC FINDINGS IN THREE DOGS WITH PANCREATIC INSULINOMA

  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.
• Lesion Type Classification by Applying Machine-Learning Technique to Contrast-Enhanced Ultrasound Images

  Kazuya Takagi, Satoshi Kondo, Kensuke Nakamura, Mitsuyoshi Takiguchi

  IEICE TRANSACTIONS ON INFORMATION AND SYSTEMS E97D 11 2947 - 2954 2014年11月 [査読有り][通常論文]
   

  One of the major applications of contrast-enhanced ultrasound (CEUS) is lesion classification. After contrast agents are administered, it is possible to identify a lesion type from its enhancement pattern. However, CEUS image reading is not easy because there are various types of enhancement patterns even for the same type of lesion, and clear classification criteria have not yet been defined. Some studies have used conventional time intensity curves (TICs), which show the vessel dynamics of a lesion. It is possible to predict lesion type from the TIC parameters, such as the coefficients obtained by curve fitting, peak intensity, flow rate and time to peak. However, these parameters are not always provide sufficient accuracy. In this paper, we prepare 1D Haar-like features which describe intensity changes in a TIC and adopt the Adaboost machine learning technique, which eases understanding of which features are useful. Hyperparameters of weak classifiers, e.g., the step size of a Haar-like filter length and threshold for output of the filter, are optimized by searching for those parameters that give the best accuracy. We evaluate the proposed method using 36 focal splenic lesions in canines 16 of which were benign and 20 malignant. The accuracies were 91.7% (33/36) when inspected by an experienced veterinarian, 75.0% (27/36) by linear discriminant analysis (LDA) using conventional three TIC parameters: time to peak, area under curve and peak intensity, and 91.7% (33/36) using our proposed method. McNemar testing shows the p-value to be less than 0.05 between the proposed method and LDA. This result shows the statistical significance of differences between the proposed method and the conventional TIC analysis method using LDA.
• Evaluation of Selected Cytokine Gene Expression in Colonic Mucosa from Dogs with Idiopathic Lymphocytic-plasmacytic Colitis

  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.
• In vitro and in vivo safety and efficacy Studies of amphotericin B on Babesia gibsoni

  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.
• Case report: Protein-losing enteropathy caused by Mesocestoides vogae (syn. M. corti) in a dog

  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.
• First detection of Echinococcus multilocularis infection in two species of nonhuman primates raised in a zoo: A fatal case in Cercopithecus diana and a strongly suspected case of spontaneous recovery in Macaca nigra

  Kimiaki Yamano, Hirokazu Kouguchi, Kohji Uraguchi, Takeshi Mukai, Chikako Shibata, Hideaki Yamamoto, Noboru Takaesu, Masaki Ito, Yoshinori Makino, Mitsuyoshi Takiguchi, Kinpei Yagi

  PARASITOLOGY INTERNATIONAL 63 4 621 - 626 2014年08月 [査読有り][通常論文]
   

  The causative parasite of alveolar echinococcosis, Echinococcus multilocularis, maintains its life cycle between red foxes (Vulpes vulples, the definitive hosts) and voles (the intermediate hosts) in Hokkaido, Japan. Primates, including humans, and some other mammal species can be infected by the accidental ingestion of eggs in the feces of red foxes. In August 2011, a 6-year-old zoo-raised female Diana monkey (Cercopithecus diana) died from alveolar echinococcosis. E. multilocularis infection was confirmed by histopathological examination and detection of the E. multilocularis DNA by polymerase chain reaction (PCR). A field survey in the zoo showed that fox intrusion was common, and serodiagnosis of various nonhuman primates using western blotting detected a case of a 14-year-old female Celebes crested macaque (Macaca nigra) that was weakly positive for E. multilocularis. Computed tomography revealed only one small calcified lesion (approximately 8 mm) in the macaque's liver, and both western blotting and enzyme-linked immunosorbent assay (ELISA) showed a gradual decline of antibody titer. These findings strongly suggest that the animal had recovered spontaneously. Until this study, spontaneous recovery from E. multilocularis infection in a nonhuman primate had never been reported. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
• Expression of apical junction complex proteins in duodenal mucosa of dogs with inflammatory bowel disease

  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.
• Qualitative and Quantitative Contrast-Enhanced Ultrasonographic Assessment of Cerulein-Induced Acute Pancreatitis 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.
• CD4⁺ T cell cytokine gene and protein expression in duodenal mucosa of dogs with inflammatory bowel disease.

  Ohta H, Takada K, Sunden Y, Tamura Y, Osuga T, Lim SY, Murakami M, Sasaki N, Wickramasekara, Rajapakshage BK, Nakamura K, Yamasaki M, Takiguchi M

  The Journal of veterinary medical science / the Japanese Society of Veterinary Science 76 3 409 - 414 2014年03月 [査読有り][通常論文]
   

  Inflammatory bowel disease (IBD) is a common cause of chronic gastrointestinal signs in dogs. In humans, T helper cells have important roles in the pathogenesis of IBD. In contrast, no specific involvement of a distinct T cell subset has been described in canine IBD. The present study evaluated the gene and protein expression of cytokines of T cell subsets in duodenal mucosa from dogs with IBD. Relative quantification of interleukin (IL)-17A, interferon (IFN)-gamma, IL-4 and IL-10 mRNA transcription was performed using duodenal mucosa from 27 IBD dogs and 8 controls. Duodenal mucosal IL-17A, IFN-gamma and IL-10 protein levels were determined by ELISA in 15 IBD dogs and 8 controls. There was no significant difference in each cytokines mRNA transcription level between groups. There was no significant difference in IL-17A, IFN-gamma and IL-10 protein expression levels between groups. Thus, there is no clear evidence for the involvement of distinct Th cytokine in the pathogenesis of canine IBD.
• Ultrasound image-guided therapy enhances antitumor effect of cisplatin.

  Noboru Sasaki, Nobuki Kudo, Kensuke Nakamura, Sue Yee Lim, Masahiro Murakami, W R Bandula Kumara, Yu Tamura, Hiroshi Ohta, Masahiro Yamasaki, Mitsuyoshi Takiguchi

  Journal of medical ultrasonics (2001) 41 1 11 - 21 2014年01月 [査読有り][通常論文]
   

  PURPOSE: The aim of this study was to clarify whether ultrasound image-guided cisplatin delivery with an intratumor microbubble injection enhances the antitumor effect in a xenograft mouse model. METHODS: Canine thyroid adenocarcinoma cells were used for all experiments. Before in vivo experiments, the cisplatin and microbubble concentration and ultrasound exposure time were optimized in vitro. For in vivo experiments, cells were implanted into the back of nude mice. Observed by a diagnostic ultrasound machine, a mixture of cisplatin and ultrasound contrast agent, Sonazoid, microbubbles was injected directly into tumors. The amount of injected cisplatin and microbubbles was 1 μg/tumor and 1.2 × 10(7) microbubbles/tumor, respectively, with a total injected volume of 20 μl. Using the same diagnostic machine, tumors were exposed to ultrasound for 15 s. The treatment was repeated four times. RESULTS: The combination of cisplatin, microbubbles, and ultrasound significantly delayed tumor growth as compared with no treatment (after 18 days, 157 ± 55 vs. 398 ± 49 mm(3), P = 0.049). Neither cisplatin alone nor the combination of cisplatin and ultrasound delayed tumor growth. The treatment did not decrease the body weight of mice. CONCLUSION: Ultrasound image-guided anticancer drug delivery may enhance the antitumor effects of drugs without obvious side effects.
• Prognostic Value of Left Atrial Function in Dogs with Chronic Mitral Valvular Heart Disease

  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).
• Qualitative and Quantitative Contrast Enhanced Ultrasonography of the Pancreas Using Bolus Injection and Continuous Infusion Methods in Normal Dogs

  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.
• LC-MS/MS analysis of canine lipoproteins fractionated using the ultracentrifugation-precipitation method.

  Asuka Suto, Masahiro Yamasaki, Yukari Takasaki, Yasuyuki Fujita, Riichiro Abe, Hiroshi Shimizu, Hiroshi Ohta, Mitsuyoshi Takiguchi

  The Journal of veterinary medical science 75 11 1471 - 7 2013年11月 [査読有り][通常論文]
   

  Due to the lack of a gold standard method in canine lipoprotein analysis, it is unclear whether canine high-density lipoprotein (HDL) and low-density lipoprotein (LDL) can be accurately evaluated by the lipoprotein analysis methods used for dogs. This study investigated whether the ultracentrifugation-precipitation (U-P) method was suitable as a gold standard method for analyzing canine lipoprotein. First, the U-P method was compared with a gel permeation high-performance liquid chromatography system (GP-HPLC). The concentrations of canine HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) determined by the U-P method correlated closely with those determined by GP-HPLC. However, the canine HDL-C concentration determined by the U-P method was lower than that determined by GP-HPLC, and the canine LDL-C concentration determined by the U-P method was higher than that determined by GP-HPLC. This study showed that some canine HDL could be precipitated with heparin manganese chloride solution. Second, the HDL and LDL fractions separated by the U-P method were analyzed by LC-MS/MS. The HDL fraction was found to contain only apolipoprotein A-I, which is an apolipoprotein of HDL, whereas the LDL fraction contained both apolipoprotein A-I and apolipoprotein B-100, which is an apolipoprotein of LDL. This data showed that a certain lipoprotein that includes apolipoprotein A-I might precipitate with canine LDL when using heparin manganese chloride solution. These results indicated that the U-P method is not currently a gold standard method for analyzing canine lipoproteins.
• Markedly increased expression of interleukin-8 in the colorectal mucosa of inflammatory colorectal polyps in miniature dachshunds

  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.
• Expression of CD4(+) T cell cytokine genes in the colorectal mucosa of inflammatory colorectal polyps in miniature dachshunds

  Hiroshi Ohta, Kanae Takada, Shidow Torisu, Masashi Yuki, Yu Tamura, Nozomu Yokoyama, Tatsuyuki Osuga, Sue Yee Lim, Masahiro Murakami, Noboru Sasaki, Kensuke Nakamura, Masahiro Yamasaki, Mitsuyoshi Takiguchi

  VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY 155 4 259 - 263 2013年10月 [査読有り][通常論文]
   

  Inflammatory colorectal polyps (ICRPs) in miniature dachshunds are 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 a space-occupying large polyp in the colorectal area, and are thought to be a novel form of inflammatory bowel disease (IBD). In humans, specific cytokine patterns attributed to T helper (Th)1, Th17 and regulatory T cells have important roles in the pathogenesis of IBD. Thus, the aim of the present study was to assess the gene expression of cytokines of T cell subsets in the colorectal mucosa from dogs with ICRPs. Colorectal mucosal specimens from 10 dogs with ICRPs and 14 control dogs were used in this study. Interferon (IFN)-gamma, interleukin (IL)-4, IL-17A and IL-10 mRNA expression was assessed using quantitative real-time PCR. IL-17A mRNA expression was significantly increased in large polyps compared to small polyps and controls. IFN-gamma and IL-10 mRNA expression in large polyps were significantly higher than in controls. There was no significant difference in IL-4 mRNA expression among the three groups. IL-17A is thought to play important roles in the pathogenesis of ICRPs. IL-10 up-regulation could oppose the proinflammatory function of IL-17A. (C) 2013 Elsevier B.V. All rights reserved.
• Increased intratumoral fluorothymidine uptake levels following multikinase inhibitor sorafenib treatment in a human renal cell carcinoma xenograft model

  Masahiro Murakami, Songji Zhao, Yan Zhao, Wenwen Yu, Chowdhury Nusrat Fatema, Ken-Ichi Nishijima, Masahiro Yamasaki, Mitsuyoshi Takiguchi, Nagara Tamaki, Yuji Kuge

  Oncology Letters 6 3 667 - 672 2013年09月 [査読有り][通常論文]
   

  An early identification of the tumor response to sorafenib treatment is indispensable for selecting optimal personalized treatment strategies. However, at present, no reliable predictors are clinically available. 18F-fluorothymidine (18F-FLT) positron emission tomography (PET) is used to assess tumor proliferation, since the FLT uptake level reflects thymidine kinase-1 (TK-1) activity. Thus, the present study determined whether FLT was able to evaluate the early tumor response to sorafenib treatment in a human renal cell carcinoma (RCC A498) xenograft in comparison with the tumor proliferation marker, Ki-67. Mice bearing A498 tumors were assigned to the control and sorafenib-treated groups and the tumor volume was measured every day. [Methyl-3H(N)]-3′-fluoro-3′-deoxythymidine (3H-FLT) was injected 2 h prior to the sacrifice of the mice on days three and seven following the treatment. 3H-FLT autoradiography (ARG) and Ki-67 immunohistochemistry (IHC) were performed using tumoral 3H-FLT uptake level diffusely increased following the treatment, while no significant changes were observed in Ki-67 IHC. The intratumoral 3H-FLT uptake levels significantly increased by 2.7- and 2.6-fold on days three and seven following the treatment, while the tumor volume and Ki-67 index did not significantly change. Thus, an increased FLT uptake level was demonstrated following the treatment, which may indicate the suppression of thymidylate synthase (TS) and the compensatory upregulation of TK-1 activity by sorafenib.
• Repeatability and reproducibility of measurements obtained via two-dimensional speckle tracking echocardiography of the left atrium and time-left atrial area curve analysis in healthy dogs

  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)
• Evaluation of changes in the tumor microenvironment after sorafenib therapy by sequential histology and F-18-fluoromisonidazole hypoxia imaging in renal cell carcinoma

  Masahiro Murakami, Songji Zhao, Yan Zhao, Nusrat Fatema Chowdhury, Wenwen Yu, Ken-Ichi Nishijima, Mitsuyoshi Takiguchi, Nagara Tamaki, Yuji Kuge

  INTERNATIONAL JOURNAL OF ONCOLOGY 41 5 1593 - 1600 2012年11月 [査読有り][通常論文]
   

  The mechanistic dissociation of 'tumor starvation' versus 'vascular normalization' following anti-angiogenic therapy is a subject of intense controversy in the field of experimental research. In addition, accurately evaluating changes of the tumor microenvironment after anti-angiogenic therapy is important for optimizing treatment strategy. Sorafenib has considerable anti-angiogenic effects that lead to tumor starvation and induce tumor hypoxia in the highly vascularized renal cell carcinoma (RCC) xenografts. F-18-fluoromisonidazole (F-18-FMISO) is a proven hypoxia imaging probe. Thus, to clarify early changes in the tumor microenvironment following anti-angiogenic therapy and whether F-18-FMISO imaging can detect those changes, we evaluated early changes in the tumor microenvironment after sorafenib treatment in an RCC xenograft by sequential histological analysis and F-18-FMISO autoradiography (ARG). A human RCC xenograft (A498) was established in nude mice, for histological studies and ARG, and further assigned to the control and sorafenib-treated groups (80 mg/kg, per os). Mice were sacrificed on Days 1, 2, 3 and 7 in the histological study, and on Days 3 and 7 in ARG after sorafenib treatment. Tumor volume was measured every day. F-18-FMISO and pimonidazole were injected intravenously 4 and 2 h before sacrifice, respectively. Tumor sections were stained with hematoxylin and eosin and immunohistochemically with pimonidazole and CD31. Intratumoral F-18-FMISO distribution was quantified in ARG. Tumor volume did not significantly change on Day 7 after sorafenib treatment. In the histological study, hypoxic fraction significantly increased on Day 2, mean vessel density significantly decreased on Day 1 and necrosis area significantly increased on Day 2 after sorafenib treatment. Intratumoral F-18-FMISO distribution significantly increased on Days 3 (10.2-fold, p<0.01) and 7 (4.1-fold, p<0.01) after sorafenib treatment. The sequential histological evaluation of the tumor microenvironment clarified tumor starvation in A498 xenografts treated with sorafenib. F-18-FMISO hypoxia imaging confirmed the tumor starvation. F-18-FMISO PET may contribute to determine an optimum treatment protocol after anti-angiogenic therapy.
• Link between inflammation and aquaporin-5 distribution in submandibular gland in sjögren's syndrome?

  M. S. Soyfoo, A. Konno, N. Bolaky, J. S. Oak, D. Fruman, C. Nicaise, M. Takiguchi, C. Delporte

  Oral Diseases 18 6 568 - 574 2012年09月 [査読有り][通常論文]
   

  Oral Diseases (2012) 18, 568-574 Objective: To determine whether a link exists between inflammation and aquaporin-5 distribution in submandibular glands from three animal models for Sjögren's syndrome: IQI/JIC, r1ΔT/r2n and non-obese diabetic mice. Methods: Mice of different ages were used. Inflammatory infiltrates were quantified using the focus score. Acinar aquaporin-5 subcellular distribution was determined by immunohistochemistry and quantified using labelling indices. Results: Minor inflammatory infiltrates were present in r1f/r2n mice. Massive inflammatory infiltrates and acinar destruction were observed in 24-week-old non-obese diabetic mice, 10-and 13-month-old IQI/JIC mice and some r1ΔT/r2n mice. Aquaporin-5 immunoreactivity was primarily apical in submandibular glands from 8- and 24-week-old Balb/C mice, 8-week-old non-obese diabetic mice, 2-, 4- and 7-month-old IQI/JIC mice and r1f/r2n mice. In contrast, decreased apical aquaporin-5 labelling index with concomitant increased apical-basolateral, apical-cytoplasmic and/or apical-basolateral-cytoplasmic aquaporin-5 labelling indices was observed in 24-week-old non-obese diabetic, 10- and 13-month-old IQI/JIC and r1ΔT/r2n mice with a focus score≥1. Conclusions: Altered aquaporin-5 distribution in submandibular acinar cells from IQI/JIC, non-obese diabetic and r1ΔT/r2n mice with a focus score≥1 appears to be concomitant to the presence of inflammatory infiltrates and acinar destruction. © 2012 John Wiley & Sons A/S.
• Involvement of Mitochondrial Genes of Babesia gibsoni in Resistance to Diminazene Aceturate

  Bandula Kumara Wickramasekara Rajapakshage, Masahiro Yamasaki, Shiang-Jyi Hwang, Noboru Sasaki, Masahiro Murakami, Yu Tamura, Sue Yee Lim, Kensuke Nakamura, Hiroshi Ohta, Mitsuyoshi Takiguchi

  JOURNAL OF VETERINARY MEDICAL SCIENCE 74 9 1139 - 1148 2012年09月 [査読有り][通常論文]
   

  The stability of the characteristics of the diminazene aceturate (DA)-resistant B. gibsoni isolate was initially determined in vitro. Part of the DA-resistant B. gibsoni isolate was cultured without DA for 4 weeks, and then newly exposed to 200 ng/m/ DA. As a result, this isolate could proliferate the same as the DA-resistant isolate, indicating that the characteristic of DA resistance was stable in the DA-resistant isolate. Additionally, the level of parasitemia in the DA-resistant isolate was comparatively lower than in the wild-type, suggesting that the proliferation potential of the DA-resistant isolate would be lower than that of the wild-type. Subsequently, to investigate the involvement of mitochondrial DNA (mtDNA) in DA resistance in B. gibsoni, the nucleotide sequences and deduced amino acid sequences of mitochondrial genes such as COXI, COXIII, and CYTb genes of the DA-resistant isolate, were compared with those of the wild-type. As a result, these three genes were not altered in the DA-resistant B. gibsoni isolate. Moreover, the transcription levels of COXI,COXIII, and CYTb genes were observed by semi-quantitative RT-PCR. As a result, the gene transcription of those genes in the DA-resistant isolate was not significantly altered. These results indicated that DA did not affect mtDNA directly in DA-resistant B. gibsoni. Thus, it is suggested that mtDNA should not be deeply involved in DA resistance in B. gibsoni.
• Bilateral Segmental Aplasia with Unilateral Uterine Horn Torsion in a Pomeranian Bitch

  Kensuke Nakamura, Masahiro Yamasaki, Tomohiro Osaki, Hiroshi Ohta, Noboru Sasaki, Keisuke Aoshima, Takashi Kimura, Mitsuyoshi Takiguchi

  JOURNAL OF THE AMERICAN ANIMAL HOSPITAL ASSOCIATION 48 5 327 - 330 2012年09月 [査読有り][通常論文]
   

  Bilateral segmental aplasia of the uterine horns with unilateral pyometra and uterine horn torsion were diagnosed in a Pomeranian bitch that presented with chronic abdominal distension and an acute onset of anorexia and lethargy. Because radiographic and ultrasonographic findings revealed the presence of markedly enlarged bilateral uterine horns filled with fluid in the caudal abdomen, a tentative diagnosis of either pyometra or hydrometra with uterine horn torsion was made. Exploratory laparotomy showed bilateral, segmentally distended uterine horns with unilateral uterine horn torsion. Ovariohysterectomy was performed, and bilateral segmental aplasia of the uterine horns with the development of unilateral uterine horn torsion was diagnosed histopathologically. To the authors' knowledge, this is the first report of uterine horn torsion in conjunction with segmental aplasia of the uterine horn in a bitch. (J Am Anim Hosp Assoc 2012; 48:327-330. DOI 10.5326/JAAHA-MS-5771)
• Analysis of energy generation and glycolysis pathway in diminazene aceturate-resistant Babesia gibsoni isolate in vitro

  Bandula Kumara Wickramasekara Rajapakshage, Masahiro Yamasaki, Masahiro Murakami, Yu Tamura, Sue Yee Lim, Tatsuyuki Osuga, Noboru Sasaki, Kensuke Nakamura, Hiroshi Ohta, Mitsuyoshi Takiguchi

  JAPANESE JOURNAL OF VETERINARY RESEARCH 60 2-3 51 - 61 2012年08月 [査読有り][通常論文]
   

  In our previous study, the level of parasitemia of the diminazene aceturate (DA)-resistant B. gibsoni isolate was continuously lower than that of the wild-type, indicating the possible alteration of energy metabolism in that isolate. Therefore, in the present study, the concentrations of ATP, glucose, lactate, and pyruvate, and the activities of lactate dehydrogenase and pyruvate kinase in the wild-type and DA-resistant isolate of B. gibsoni were measured and compared to investigate the amount of energy generation and the activity of the glycolysis pathway. As a result, the intracellular ATP and glucose concentrations in the DA-resistant B. gibsoni isolate were significantly higher than those in the wild-type. Meanwhile, the concentrations of lactate and pyruvate and the activities of lactate dehydrogenase and pyruvate kinase in the DA-resistant B. gibsoni isolate were not different from those in the wild-type. These results indicated that the DA-resistant B. gibsoni isolate contained a higher ATP concentration than the wild-type, but the activity of the glycolysis pathway was not altered in the DA-resistant B. gibsoni isolate. However, we could not determine the mechanism of the high energy production of the DA-resistant B. gibsoni isolate. Further studies on the energy metabolism of B. gibsoni are necessary to clarify the mechanism of the high energy production in the DA-resistant B. gibsoni isolate.
• Enhanced Cytotoxic Effect of Cisplatin Using Diagnostic Ultrasound and Microbubbles In Vitro

  Sasaki Noboru, Nakamura Kensuke, Murakami Masahiro, Lim Sue Yee, Ohta Hiroshi, Yamasaki Masahiro, Takiguchi Mitsuyoshi

  11TH INTERNATIONAL SYMPOSIUM ON THERAPEUTIC ULTRASOUND 1481 307 - 310 2012年 [査読有り][通常論文]
  
• ACTIVATION OF MICROBUBBLES BY SHORT-PULSED ULTRASOUND ENHANCES THE CYTOTOXIC EFFECT OF CIS-DIAMMINEDICHLOROPLATINUM (II) IN A CANINE THYROID ADENOCARCINOMA CELL LINE IN VITRO

  Noboru Sasaki, Nobuki Kudo, Kensuke Nakamura, Sue Yee Lim, Masahiro Murakami, W. R. Bandula Kumara, Yu Tamura, Hiroshi Ohta, Masahiro Yamasaki, Mitsuyoshi Takiguchi

  ULTRASOUND IN MEDICINE AND BIOLOGY 38 1 109 - 118 2012年01月 [査読有り][通常論文]
   

  Ultrasound targeted microbubble destruction has succeeded in delivering drugs and genes. This study was designed to explore characteristics of ultrasound targeted microbubble destruction using short-pulsed diagnostic ultrasound. Canine thyroid adenocarcinoma cells were exposed to short-pulsed diagnostic ultrasound in the presence of cis-diamminedichloroplatinum (II) (cisplatin) and ultrasound contrast agent Sonazoid (R) microbubbles. The cytotoxic effect of cisplatin was enhanced by short-pulsed diagnostic ultrasound and microbubbles. Incubation time with microbubbles influenced the cytotoxic effect of cisplatin. However, exposure duration did not affect the cytotoxic effect of cisplatin. Therefore, short-pulsed diagnostic ultrasound may activate microbubbles near cells and deliver cisplatin into cells. In addition, activation of microbubbles may be concluded in a short time. Our results suggest that short exposure duration could be potentially sufficient to induce efficient drug delivery by ultrasound targeted microbubble destruction using short-pulsed diagnostic ultrasound. (E-mail: mtaki@vetmed.hokudai.ac.jp) (C) 2012 World Federation for Ultrasound in Medicine & Biology.
• Effects and Mechanisms of Action of Polyene Macrolide Antibiotic Nystatin on Babesia gibsoni In Vitro

  Masahiro Yamasaki, Norihisa Tamura, Kensuke Nakamura, Noboru Sasaki, Masahiro Murakami, Wickramasekara Rajapakshage, Bandula Kumara, Yu Tamura, Sue Yee Lim, Hiroshi Ohta, Mitsuyoshi Takiguchi

  JOURNAL OF PARASITOLOGY 97 6 1190 - 1192 2011年12月 [査読有り][通常論文]
   

  Nystatin is a membrane-active polyene macrolide antibiotic and a channel-forming ionophore. Nystatin exhibits in vitro activity against Babesia gibsoni infecting normal canine erythrocytes containing low potassium (LK) and high sodium concentrations, i.e., LK erythrocytes. The calculated IC(50) value of nystatin against B. gibsoni infecting LK erythrocytes was 31.96 mu g/ml. The anti-babesial activity of nystatin disappeared when B. gibsoni in LK erythrocytes were incubated in culture media containing high potassium concentrations (HK). Moreover, when the parasites were harbored in canine HK erythrocytes, which contained high potassium and low sodium concentrations as a result of high Na-K-ATPase activity, the in vitro anti-babesial activities of nystatin also disappeared, apparently due to protection by HK erythrocytes. This suggested that nystatin could show in vitro anti-babesial activity against B. gibsoni by its ionophorous activity, the same as other ionophores such as valinomycin. Subsequently, the effects of nystatin on the host cells were observed. Nystatin could not modify the intracellular concentrations of potassium, sodium, adenosine triphosphate, or glucose in either LK or HK erythrocytes, although it caused weak hemolysis in HK erythrocytes. In addition, nystatin did not affect the survival of canine peripheral polymorphonuclear leukocytes. In conclusion, nystatin destroyed B. gibsoni by ionophorous activity but did not affect either canine erythrocytes or leukocytes in vitro.
• Effects of sildenafil citrate on five dogs with Eisenmenger's syndrome

  K. Nakamura, M. Yamasaki, H. Ohta, N. Sasaki, M. Murakami, W. R. Bandula Kumara, M. Takiguchi

  JOURNAL OF SMALL ANIMAL PRACTICE 52 11 595 - 598 2011年11月 [査読有り][通常論文]
   

  Objectives: To determine the effect of sildenafil for dogs with Eisenmeger's syndrome and secondary erythrocytosis.
• Pathological correlations between podocyte injuries and renal functions in canine and feline chronic kidney diseases.

  Ichii O, Yabuki A, Sasaki N, Otsuka S, Ohta H, Yamasaki M, Takiguchi M, Namiki Y, Hashimoto Y, Endoh D, Kon Y

  Histology and histopathology 26 10 1243 - 1255 Universidad de Murcia 2011年10月 [査読有り][通常論文]
   

  Podocytes cover the glomerulus and their adjacent foot processes form a principal barrier called the slit diaphragm. Podocyte dysfunctions, including podocyte loss and slit diaphragm disruptions, induce chronic kidney diseases (CKD). In this study, we analyzed the correlations between podocyte injuries and renal dysfunctions in domestic carnivores. Dogs and cats were divided into normal and CKD groups according to renal histopathology and plasma creatinine values. Immunostaining results showed that linear reactions of slit diaphragm molecules, e.g., nephrin, podocin, and ACTN4, were parallel to glomerular capillaries in all animals. However, in dogs, reactions of nephrin and ACTN4 were changed to a granular pattern in the CKD group, and their intensities significantly decreased with the number of podocytes in the glomerulus. Moreover, the expression of nephrin and ACTN4 negatively correlated with creatinine. Real-time PCR analysis showed that nephrin mRNA expression in the kidneys of CKD dogs was significantly lower than that in normal animals, and negatively correlated with creatinine. Although no significant correlation between renal dysfunction and podocyte injury was detected in cats, histoplanimetric scores of tubulointerstitial lesions in CKD cats were higher than those in both normal cats and diseased dogs. Furthermore, mRNAs of WT1 and SD molecules were detected in urine from CKD animals. In conclusion, podocyte injuries such as podocytopenia and decreased expression of nephrin and ACTN4 in the glomerulus were more strongly correlated with renal dysfunction in dogs than in cats. These findings suggest that the CKD pathogenesis, especially susceptibilities to podocyte injuries, differed between dogs and cats.
• Detection of anti-Babesia gibsoni heat shock protein 70 antibody and anti-canine heat shock protein 70 antibody in sera from Babesia gibsoni-infected dogs

  Masahiro Yamasaki, Mikiko Ishida, Kensuke Nakamura, Noboru Sasaki, Masahiro Murakami, Wickramasekara Rajapakshage Bandula Kumara, Yu Tamura, Sue Yee Lim, Hiroshi Ohta, Mitsuyoshi Takiguchi

  VETERINARY PARASITOLOGY 180 3-4 215 - 225 2011年08月 [査読有り][通常論文]
   

  Antibodies that recognized either Babesia gibsoni or canine red blood cell (RBC) 70-kilodalton (kDa) protein were detected in serum from acutely and chronically B. gibsoni-infected. In those sera, antibodies that reacted with recombinant B. gibsoni and canine heat shock protein 70 (rBgHsp70 and rcHsp70) were detected; therefore, B. gibsoni and canine RBC 70-kDa proteins seemed to be BgHsp70 and cHsp70, respectively. In infected dogs, the amounts of these antibodies increased after infection. Interestingly, polyclonal antibody raised against rBgHsp70 in two rabbits reacted not only with rBgHsp70 but also with rcHsp70 and native cHsp70 from canine RBCs. Because BgHsp70 showed high homology with cHsp70 (70.8%), anti-rBgHsp70 antibody might cross-react with cHsp70. Additionally, the localizations of both BgHsp70 and cHsp70 were observed by indirect fluorescence assay. As a result, cHsp70 was not found on the membrane surface of erythrocytes, suggesting that erythrocytes would not be targets of anti-cHsp70 antibody. Meanwhile, only exoerythrocytic parasites were stained by anti-rBgHsp70 antibody. This result showed that BgHsp70 would be expressed on the surface of parasites during the exoerythrocytic stage. These results indicated that BgHsp70 was a highly immunogenic protein in canine B. gibsoni infection, and that exoerythrocytic parasites might be targets of anti-BgHsp70 antibody. (C) 2011 Elsevier B.V. All rights reserved.
• Expression and subcellular localization of apical junction proteins in canine duodenal and colonic mucosa

  Hiroshi Ohta, Tomoki Yamaguchi, B. K. Wickramasekara Rajapakshage, Masahiro Murakami, Noboru Sasaki, Kensuke Nakamura, Shiang-Jyi Hwang, Masahiro Yamasaki, Mitsuyoshi Takiguchi

  AMERICAN JOURNAL OF VETERINARY RESEARCH 72 8 1046 - 1051 2011年08月 [査読有り][通常論文]
   

  Objective-To examine the expression and distribution of tight junction (TJ) and adherens junction (AM proteins in canine duodenal and colonic mucosa. Sample-Mucosa obtained from 4 healthy Beagles. Procedures-Biopsy specimens of the duodenum and colon were obtained via endoscopy from 4 healthy dogs. The expression patterns and subcelluar localization of claudin-1, -2, -3, -4, -5, -7, and -8; E-cadherin; and beta-catenin in the duodenum and colon were analyzed by use of immunoblotting and immunofluorescence microscopy. Results-In the duodenum, there was clear expression of claudin-3 and -5, E-cadherin, and beta-catenin proteins and weak expression of claudin-7 protein. In contrast, there was clear expression of claudin-2 and -3, E-cadherin, and beta-catenin proteins and weak expression of claudin-5 and -7 proteins in the colon, as determined by use of immunoblotting. As determined by the use of immunofluorescence microscopy, the duodenum and colon had staining for claudin-3 and -5, E-cadherin, and beta-catenin in the most apical region and staining for claudin-7 in the basolateral region. Staining for claudin-2 was also observed in the colon. Conclusions and Clinical Relevance-Information was provided about the expression patterns of TJ and AJ proteins in the duodenum and colon of clinically normal dogs. These results may provide valuable information for use in evaluating the importance of these TJ and AJ proteins in the pathogenesis of inflammatory bowel disease in dogs. (Am J Vet Res 2011;72:1046-1051)
• Altered expression of miR-146a correlates with the development of chronic renal inflammation.

  Ichii O, Yabuki A, Sasaki N, Otsuka S, Ohta H, Yamasaki M, Takiguchi M, Namiki Y, Hashimoto Y, Endoh D, Kon Y

  Kidney Int. 81 3 280 - 292 2011年 [査読有り][通常論文]
  
• Babesia gibsoni: Detection in blood smears and formalin-fixed, paraffin-embedded tissues using deoxyribonucleic acid in situ hybridization analysis

  Masahiro Yamasaki, Yusuke Kobayashi, Kensuke Nakamura, Noboru Sasaki, Masahiro Murakami, Bandula Kumara Wickramasekara Rajapakshage, Hiroshi Ohta, Osamu Yamato, Yoshimitsu Maede, Mitsuyoshi Takiguchi

  EXPERIMENTAL PARASITOLOGY 127 1 119 - 126 2011年01月 [査読有り][通常論文]
   

  In this study, we attempted to detect Babesia gibsoni in blood smears and formalin-fixed, paraffin-embedded tissues obtained from B. gibsoni-infected dogs using in situ hybridization. Using a digoxigenin-conjugated deoxyribonucleic acid (DNA) probe, both intraerythrocytic and exoerythrocytic parasites in the culture could be specifically stained in blood smears fixed with 4% phosphate-buffered paraformaldehyde. This indicated that genomic DNA extracted from the parasites could be detected using in situ hybridization. Moreover, the parasite could be specifically stained in paraffin-embedded spleen, lymph node, and kidney sections using in situ hybridization. Infected erythrocytes in blood vessels in the spleen and kidney, hemosiderin-laden macrophages in the spleen, and phagocytized erythrocytes, which seemed to be infected with the parasites, in lymph nodes were also specifically stained. This suggests that in situ hybridization can be utilized to investigate both the life cycle of B. gibsoni and the pathological condition of canine babesiosis. (C) 2010 Elsevier Inc. All rights reserved.
• Contrast-enhanced ultrasonography for characterization of focal splenic lesions in dogs.

  Nakamura K, Sasaki N, Murakami M, Bandula Kumara WR, Ohta H, Yamasaki M, Takagi S, Osaki T, Takiguchi M

  Journal of veterinary internal medicine / American College of Veterinary Internal Medicine 24 6 1290 - 1297 6 2010年11月 [査読有り][通常論文]
   

  Nakamura K, Sasaki N, Murakami M, Bandula Kumara WR, Ohta H, Yamasaki M, Takagi S, Osaki T, Takiguchi M, <i>Journal of veterinary internal medicine / American College of Veterinary Internal Medicine</i>, 2010, vol. 24, no. 6, pp. 1290-1297
• Reduced transcript levels of the heat shock protein 70 gene in diminazene aceturate-resistant Babesia gibsoni variants under low concentrations of diminazene aceturate

  Shiang-Jyi Hwang, Masahiro Yamasaki, Kensuke Nakamura, Noboru Sasaki, Masahiro Murakami, Bandula Kumara Wickramasekara Rajapakshage, Hiroshi Ohta, Yoshimitsu Maede, Mitsuyoshi Takiguchi

  JAPANESE JOURNAL OF VETERINARY RESEARCH 58 3-4 155 - 164 2010年11月 [査読有り][通常論文]
   

  In our previous report, we developed a diminazene aceturate (DA)-resistant Babesia gibsoni strain that was maintained in culture with 200 ng/ml DA. While developing this strain, we also obtained DA-resistant B. gibsoni variants, which were maintained in culture with DA from 1 to 175 ng/ml for more than 8 weeks. Because heat shock protein 70 (Hsp70) seems to play important roles in adaptation to a stress environment in protozoan parasites, in the present study, we examined the copy number of B. gibsoni Hsp70 (BgHsp70) transcripts of those DA-resistant variants using quantitative real-time reverse transcription-polymerase chain reaction. We found that when wild-type B. gibsoni was exposed to 1 ng/ml DA, the level of BgHsp70 transcripts was decreased at day 14. The copy number of BgHsp70 transcripts in the DA-resistant variant cultured with 1 ng/ml DA was significantly lower than in wild-type B. gibsoni, while those in DA-resistant variants increased with escalating doses of DA from 1 to 75 ng/ml, although they were lower than in wild-type B. gibsoni. However, those in DA-resistant variants cultured with > 125 ng/ml DA were almost the same as wild-type B. gibsoni. These results indicated that the transcript levels of the BgHsp70 gene might be reduced when the parasites are exposed to a low concentration of DA, and then might recover to the normal level after achieving resistance against DA. We expect that further study of the function of BgHsp70 will elucidate the mechanism of drug resistance against DA in B. gibsoni.
• Development and Characterization of a Strain of Babesia gibsoni Resistant to Diminazene Aceturate In Vitro

  Shiang-Jyi Hwang, Masahiro Yamasaki, Kensuke Nakamura, Noboru Sasaki, Masahiro Murakami, Bandula Kumara Wickramasekara Rajapakshage, Hiroshi Ohta, Yoshimitsu Maede, Mitsuyoshi Takiguchi

  JOURNAL OF VETERINARY MEDICAL SCIENCE 72 6 765 - 771 2010年06月 [査読有り][通常論文]
   

  We attempted to develop a strain of Babesia gibsoni resistant to diminazene aceturate (DA), an anti-babesial drug, in vitro. Since the DA-sensitive B. gibsoni strain could survive and proliferate in culture medium containing 1 ng/ml DA, the concentration of DA was gradually increased from 1 to 200 ng/ml. The results showed that the parasites could survive and proliferate in the medium containing 200 ng/ml DA, which was much higher than the 50% inhibitory concentration (IC(50)) of DA for B. gibsoni. Subsequently, these parasites were removed from erythrocytes and exposed directly to 200 ng/ml DA. They were able to survive and invade fresh erythrocytes, though the DA-sensitive B. gibsoni strain did not survive. Based on these results, the parasites cultured within 200 ng/ml DA were determined to be a DA-resistant B. gibsoni strain. In addition, the IC(50) levels of clindamycin, doxycycline and pentamidine for the DA-resistant B. gibsoni strain were determined. The IC(50) levels of clindamycin, doxycycline and pentamidine for the DA-resistant strain were higher than those for the DA-sensitive strain. The IC(50) of pentamidine for the resistant strain was much greater than that for the DA-sensitive strain. These results indicated that the DA-resistant B. gibsoni strain could have resistance not only to DA, but also to other anti-babesial drugs. In conclusion, we successfully developed a DA-resistant B. gibsoni strain in vitro.
• Local overexpression of interleukin-1 family, member 6 relates to the development of tubulointerstitial lesions

  Osamu Ichii, Saori Otsuka, Nobuya Sasaki, Akira Yabuki, Hiroshi Ohta, Mitsuyoshi Takiguchi, Yoshiharu Hashimoto, Daiji Endoh, Yasuhiro Kon

  LABORATORY INVESTIGATION 90 3 459 - 475 2010年03月 [査読有り][通常論文]
   

  Identification of factors that exacerbate a disease is important for the development of biomarkers. In this study, we discovered ectopic overexpression of interleukin-1 family, member-6 (IL-1F6) in several murine renal diseases. IL-1F6 participates in cytokine/chemokine production in the epithelium. In PCR array analysis for inflammatory mediators, Il1f6 showed the highest expression in the kidney of the B6. MRLc1 glomerulonephritis model. IL-1F6 was localized in the epithelium from the DCTs to CCDs, which showed tubular dilations or epithelial deciduations. Ultrastructual examination of the epithelial cells revealed that IL-1F6 was localized on the cytoplasmic ribosome, vesicles, and nucleus. In and around these tubules, we found infiltrations of CD3-positive T-cells and nestin- or alpha-smooth-muscle actin-positive mesenchymal cells. Expression of the IL-1F6 protein and Il1f6 mRNA in the kidney was increased by the development of TILs in the B6. MRLc1 model and in lupus (BXSB, NZB/WF1, and MRL/lpr), nephrotic syndrome (ICGN), and streptozotocin-induced diabetic models. IL-1F6 was also detected in the epithelia having squamous or deciduous contours in other organs such as the skin, esophagus, thymus, or uterus. In vitro analysis using M-1 cells from the murine collecting duct revealed that Il1f6 mRNA induction was related to the upregulation of IL-6, TGF-beta receptor-1, and mesenchymal markers and to the downregulation of epithelial markers and changes in the squamous cells of the epithelium. Interestingly, urine Il1f6 mRNA expression was detected earlier than renal dysfunctions in these mouse models. Ectopic overexpression of IL-1F6 in kidneys is associated with TILs and especially with cell infiltrations and changes in epithelial morphology. We propose that local overexpression of IL-1F6 is related to the development of TILs.
• CONTRAST-ENHANCED ULTRASONOGRAPHY FOR CHARACTERIZATION OF CANINE FOCAL LIVER LESIONS

  Kensuke Nakamura, Satoshi Takagi, Noboru Sasaki, Wickramasekara Rajapakshage Bandula Kumara, Masahiro Murakami, Hiroshi Ohta, Masahiro Yamasaki, Mitsuyoshi Takiguchi

  VETERINARY RADIOLOGY & ULTRASOUND 51 1 79 - 85 2010年01月 [査読有り][通常論文]
   

  In six normal beagles and 27 dogs with spontaneous focal or multifocal liver lesions, contrast-enhanced ultrasonography using Sonazoid (R) was performed. Sonazoid (R) is a newly developed second-generation contrast agent with the ability to be used for real-time contrast imaging along with parenchymal imaging. An appropriate protocol for the evaluation of all three phases (arterial, portal, and parenchymal) was established based on the results for normal beagles. By evaluation of the echogenicity of hepatic nodules during the arterial and parenchymal phases it was possible to differentiate malignant tumors from benign nodules with very high accuracy. In 15 of 16 dogs diagnosed as malignant tumors, nodules were clearly hypoechoic to the surrounding normal liver during the parenchymal phase. Additionally, malignant tumors had different echogenicity compared with the surrounding normal liver during the arterial phase in 14 of 15 dogs. In the portal phase, there were no characteristic findings. Contrast-enhanced ultrasonography with Sonazoid (R) appears to improve the characterization of canine focal and multifocal hepatic lesions.
• EFFECTS AND MECHANISMS OF ACTION OF IONOPHOROUS ANTIBIOTICS VALINOMYCIN AND SALINOMYCIN-NA ON BABESIA GIBSONI IN VITRO

  Masahiro Yamasaki, Kensuke Nakamura, Norihisa Tamura, Shiang-Jyi Hwang, Muneyoshi Yoshikawa, Noboru Sasaki, Hiroshi Ohta, Osamu Yamato, Yoshimitsu Maede, Mitsuyoshi Takiguchi

  JOURNAL OF PARASITOLOGY 95 6 1532 - 1538 2009年12月 [査読有り][通常論文]
   

  Valinomycin and salinomycin-Na, 2 ionophorous antibiotics, exhibited in vitro antibabesial activities against Babesia gibsoni that infected normal canine erythrocytes containing low potassium (LK) and high sodium concentrations, i.e., LK erythrocytes, which completely lack Na,K-ATPase activity. The level of parasitemia of B. gibsoni was significantly decreased when the parasites were incubated in culture medium containing either 10(-1) ng/ml valinomycin or 10(2) ng/ml salinomycin-Na for 24 hr. Four-hour incubation in the culture medium containing 5 mu g/ml salinomycin-Na led to the destruction of most parasites. In contrast, when the parasites infected canine erythrocytes containing high potassium (HK) and low sodium concentrations, i.e., HK erythrocytes, the in vitro antibabesial activities of both ionophorous antibiotics seemed to be weakened, apparently due to the protection by the host cells. Therefore, differential influences of ionophorous antibiotics on LK and HK erythrocytes were observed. In LK erythrocytes, the intracellular concentrations of potassium, sodium, and adenosine triphosphate (ATP) were not modified, and hemolysis was not observed after incubation in the medium containing each ionophorous antibiotic. These results suggested that these ionophorous antibiotics did not affect cells without Na,K-ATPase, and directly affected B. gibsoni. In HK erythrocytes, the ionophorous antibiotics increased the intracellular sodium concentration, and decreased the intracellular potassium and ATP concentrations, causing obvious hemolysis. Additionally, the decrease of the intracellular ATP concentration and the hemolysis in HK erythrocytes caused by valinomycin disappeared when the activity of Na,K-ATPase was inhibited by ouabain. These results indicate that modification of the intracellular cation concentrations by the ionophorous antibiotics led to the activation of Na,K-ATPase and increased consumption of intracellular ATP, and that the depletion of intracellular ATP resulted in hemolysis in HK erythrocytes. Moreover, the antibabesial activity of valinomycin disappeared when B. gibsoni in LK erythrocytes were incubated in culture media containing high potassium concentrations. This showed that the intracellular cation concentration in the parasites was not modified in those media and would remain the same.
• Primary Splenic Torsion in a Boston Terrier

  Hiroshi Ohta, Satoshi Takagi, Masahiro Murakami, Noboru Sasaki, Muneyoshi Yoshikawa, Kensuke Nakamura, Shiang-Jyi Hwang, Masahiro Yamasaki, Mitsuyoshi Takiguchi

  JOURNAL OF VETERINARY MEDICAL SCIENCE 71 11 1533 - 1535 2009年11月 [査読有り][通常論文]
   

  A 7-year-old female Boston terrier was referred to Hokkaido University Veterinary Teaching Hospital with a history of hemoglobinuria and anemia for several days. Abdominal radiographs showed splenomegaly, and Ultrasonography revealed a hypoechoic splenic parenchyma with interspersed linear echoes consistent with the ultrasonographic appearance of splenic torsion. Ultrasonography and computed tomography (CT) indicated a C-shaped spleen. Exploratory laparotomy confirmed the diagnosis of splenic torsion. A splenectomy was performed, and the dog recovered well Without complications. This is the first report of splenic torsion in Boston terriers, and the usefulness of ultrasonographic and CT findings of the splenic torsion was also confirmed.
• QUANTITATIVE CONTRAST-ENHANCED ULTRASONOGRAPHY OF CANINE SPLEEN

  Kensuke Nakamura, Noboru Sasaki, Muneyoshi Yoshikawa, Hiroshi Ohta, Shiang-Jyi Hwang, Takahiro Mimura, Masahiro Yamasaki, Mitsuyoshi Takiguchi

  VETERINARY RADIOLOGY & ULTRASOUND 50 1 104 - 108 2009年01月 [査読有り][通常論文]
   

  Contrast-enhanced ultrasonography has an important role in the detection of tumors in humans. The second-generation contrast agent Sonazoid has the ability of real-time contrast imaging along with parenchymal imaging. The purposes of this study were to determine the effect and duration of Sonazoid on the changes in gray-scale enhancement of canine spleen and to establish an appropriate protocol for contrast-enhanced ultrasonography of canine spleen. Six healthy beagles were injected with an intravenous bolus of Sonazoid. In the spleen parenchyma, the enhancement was maintained up to 30 min after injection. Moreover, for 5-22 s after injection, gray-scale enhancement of splenic arteries afforded arterial imaging. Perfusion of the kidney may be investigated from 3.6 s to 3.5 min after injection of Sonazoid. These results suggest that Sonazoid is applicable to canine spleen parenchymal imaging and that the optimal time for the parenchymal imaging is 7-30 min after injection. The findings of this quantitative study should prove useful in the evaluation of diffuse or focal splenic and renal diseases in dogs.
• Flow cytometry to evaluate the level of Babesia gibsoni parasitemia in vivo and in vitro by using the fluorescent nucleic acid stain SYTO16

  Masahiro Yamasaki, Shiang-Jyi Hwang, Hiroshi Ohta, Osamu Yamato, Yoshimitsu Maede, Mitsuyoshi Takiguchi

  JAPANESE JOURNAL OF VETERINARY RESEARCH 55 4 129 - 136 2008年02月 [査読有り][通常論文]
   

  In the present study, we employed flow cytometry to evaluate the level of parasitemia of Babesia gibsoni infecting canine erythrocytes in vivo and in vitro by using fluorescent nucleic acid staining. Peripheral blood samples from a R gibsoni-infected dog and cultured B. gibsoni parasitizing in canine erythrocytes were stained with a membrane-permeable fluorescent nucleic acid stain, SYTO16. In this study, we utilized normal canine erythrocytes (LK erythrocytes) and canine erythrocytes containing high concentrations of potassium, reduced glutathione, and some free amino acids (HK erythrocytes) as host cells for culture. Parasitized cells in vivo were discriminated completely from unparasitized cells and a correlation (r = 0.998) between the percentage of SYTO16-positive cells and parasitemia in vivo was observed. On the other hand, erythrocytes in vitro could not be divided clearly into parasitized and unparasitized cells. However, when LK erythrocytes were used as host cells, the percentage of SYTO16-positive cells was almost the same as, and was well correlated (r = 0.932) with, the level of parasitemia. When HK erythrocytes were used as host cells, the percentage of SYTO16-positive cells was almost half of, but was correlated (r = 0.982) with, the level of parasitemia. Therefore, we attempted to observe the changes in the percentage of parasitized cells after treatment with antiprotozoal drug or mitochondria. inhibitors by using flow cytometry. The changes in the percentage of SYTO16-positive cells corresponded well with the changes of the level of parasitemia when the parasites in HK erythrocytes were cultured with each compound. The present results suggest that flow cytometric detection using SYTO16 is a rapid and reliable method for monitoring parasitemia both in vivo and in vitro.
• Identification of a quantitative trait locus regulating B cell-dominant infiltration into autoimmune sialitis lesions of the IQI mouse model of primary Sjögren's syndrome.

  Konno A, Takiguchi M, Takada K, Usami T, Azumi K, Kubota H, Inaba M, Saegusa J, Kon Y

  Immunogenetics 59 11 853 - 859 2007年11月 [査読有り][通常論文]
   

  Sjogren's syndrome (SS) is caused by an autoimmune sialodacryoadenitis, and up to 5% of patients with SS develop malignant B cell growth. The IQI mouse is a spontaneous model of primary SS in which B cells are the dominant cellular subpopulation among mononuclear infiltrates in sialitis lesions. Understanding the genetic control of aberrant B cell growth in IQI mice may help elucidate the genetic mechanisms involved in B-lineage hyperplasia leading to malignant transformation in human SS. B cell-dominant infiltration in the submandibular glands of 6-month-old IQI and C57BL/6 (B6) mice and their F1 and F2 progenies was quantified as B-lymphocytic sialitis score, and a genome-wide scan of 179 (IQI x B6) F2 females was performed to identify a quantitative trait locus (QTL) controlling this phenotype. A QTL significantly associated with variance in B-lymphocytic sialitis score was mapped to the D6Mit138 marker (position of 0.68cM) on proximal chromosome 6, with a logarithm of odds score of 4.3 (p=0.00005). This QTL, named autoimmune sialitis in IQI mice, associated locus 1 (Asq1), colocalized with Islet cell autoantigen 1 (Ica1), which encodes a target protein of the immune processes that define the pathogenesis of primary SS in humans and in the nonobese diabetic mouse model.
• Restricted localization of claudin-16 at the tight junction in the thick ascending limb of Henle's loop together with claudins 3, 4, and 10 in bovine nephrons

  H Ohta, H Adachi, M Takiguchi, M Inaba

  JOURNAL OF VETERINARY MEDICAL SCIENCE 68 5 453 - 463 2006年05月 [査読有り][通常論文]
   

  Claudin-16 is one of the tight junction protein claudins and has been shown to contribute to reabsorption of divalent cations in the human kidney. In cattle, total deficiency of claudin-16 causes severe renal tubular dysplasia without aberrant metabolic changes of divalent cations, suggesting that bovine claudin-16 has some roles in renal tubule formation and paracellular transport that are somewhat different from those expected from the pathology of human disease. As the first step to clarify these roles, we examined the expression and distribution of claudin-16 and several other major claudin subtypes. claudins 1-4 and 10. in bovine renal tubular segments by immunofluorescence microscopy. Claudin-16 was exclusively distributed to the tight junction in the tubular segment positive for Tamm-Horsfall glycoprotein, the thick ascending limb (TAL) of Henle's loop. and was found colocalized with claudins 3. 4. and 10. This study also demonstrates that bovine kidneys possess segment-specific expression patterns for claudins 2-1 and 10 that are different from those reported for mice. Particularly, distribution of claudin-4 in the TAL and distal convoluted tubules was characteristic of bovine nephrons as were differences in the expression patterns of claudins 2 and 3. These findings demonstrate that the total lack of claudin-16 in the TAL segment is the sole cause of renal tubular dysplasia in cattle and suggest that the tight junctions in distinct tubular segments including the TAL have barrier functions in paracellular permeability that are different among animal species.
• Magnetic resonance imaging of alveolar echinococcosis experimentally induced in the rat lung

  T Asanuma, T Kawahara, O Inanami, M Nakao, K Nakaya, A Ito, M Takiguchi, A Hashimoto, M Kuwabara

  JOURNAL OF VETERINARY MEDICAL SCIENCE 68 1 15 - 20 2006年01月 [査読有り][通常論文]
   

  Pulmonary alveolar echinococcosis (AE) caused by the metacestode of Echinococcus multilocularis is a lethal zoonosis and 14 is a lesion secondarily induced by hematogenous dissemination from hepatic AE lesions. In the present study, a hematogenous pulmonary AE model was experimentally induced in rats by the injection of echinococcal larval tissue homogenate to the tail vein, and then the pathological and diagnostic aspects of pulmonary AE were examined by magnetic resonance imaging (MRI). Histological primary, mature and degenerated AE lesions were observed 5, 18 and 50 weeks after injection, respectively. These lesions were discriminated as signal-void, hypointense and hyperintense regions in T1-weighted MRI (T1WI), respectively. The change in signal intensity in T1WI 1 might reflect the content of proteinaceous fluid as a result of AE cyst degeneration. Western blot analysis of sera with antibodies of two epitopes (Em18 and Em16) of E. multilocularis provided evidence for AE infection in the early stage. T1WI in combination with Western blot analysis could possibility become definitive and early signs of hematogenous pulmonary A-E infection.
• Different effects on the inflammatory lesions in the lacrimal and salivary glands after neonatal thymectomy in IQI/Jic mice, a model for Sjögren's syndrome.

  Takada K, Takiguchi M, Inaba M

  The Journal of veterinary medical science / the Japanese Society of Veterinary Science 67 9 955 - 957 2005年09月 [査読有り][通常論文]
   

  Thymectomy on day 3 after birth (D3Tx) is understood to eliminate CD4(+)CD25(+) regulatory T cells (T-reg) from the peripheral T cell repertoire in rodents, leading to the activation of autoreactive T cells. Herein, D3Tx was performed in IQI/Jic mice, a model for Sjogren's syndrome characterized by autoimmune infiltrations into the lacrimal and salivary glands. At the age of 16 weeks, very severe lesions were observed in lacrimal tissues from thymectornized mice, suggesting that T-reg preserve their immunoregulatory function in young IQI/Jic mice. In contrast, salivary lesions were comparable in the D3Tx and control groups, raising the possibility that either salivary-specific T-reg escaped elimination in thymectornized mice or spontaneous lesions in IQI/Jic mice developed independently of the tolerance through T-reg.
• Autoimmunity against a tissue kallikrein in IQI/Jic mice - A model for Sjogren's syndrome

  K Takada, M Takiguchi, A Konno, A Inaba

  JOURNAL OF BIOLOGICAL CHEMISTRY 280 5 3982 - 3988 2005年02月 [査読有り][通常論文]
   

  We have recently characterized IQI/Jic mice as a model for Sjogren's syndrome (SS), a chronic autoimmune disease in humans. In SS, local lymphocytic infiltrations into salivary and lacrimal glands frequently develop to the involvement of systemic exocrine and nonexocrine organs, and the mechanism for progression of this disease remains obscure. Herein, we report identification of an autoantigen shared by various target organs in IQI/Jic mice. Polypeptides identified based on immunorecognition by autoantibodies in sera from IQI/ Jic mice affected with autoimmune disease (> 12 weeks of age) were tissue kallikrein (Klk)-1 and -13 and were cross-reactive to the autoantibodies. Interestingly, Klk-13, but not Klk-1, caused a proliferative response of splenic T cells from IQI/Jic mice from the age of 4 weeks onward. In addition, remarkably enhanced expression of Klk-13 was observed in the salivary glands of the mice in accordance with the development of inflammatory lesions. These results indicate that Klk-13 acts as an autoantigen and may increase T cells responsive to organs commonly expressing Klk-13, playing a pivotal role in the etiology of progression of disease in IQI/Jic mice. Our findings provide insights into the contributions of autoantigens shared by multiple organs in the progress of SS from an organ-specific to a systemic disorder.
• Diagnostic ultrasound of polypoid cystitis in dogs

  M Takiguchi, M Inaba

  JOURNAL OF VETERINARY MEDICAL SCIENCE 67 1 57 - 61 2005年01月 [査読有り][通常論文]
   

  Polypoid cystitis is a rare disease of the urinary bladder in dogs characterized by chronic inflammation, epithelial proliferation, and development of a polypoid mass or masses without histopathologic evidence of neoplasia. The ultrasonographic appearances of eight dogs with polypoid cystitis are described. Ultrasonography confirmed the presence of a bladder mass or masses in all patients. Ultrasonographic findings are mucosal projections and a polypoid to pedunculated mass of variable size and shape. Although a polypoid mass tends to be located in the cranioventral bladder mucosa, the polyps also could arise in the craniodorsal bladder mucosa. Ultrasonographic images are well correlated with contrast radiographic studies and gross morphological appearance. Ultrasound is a non-invasive, very useful diagnostic tool for detecting bladder polyps, but histopathology is required for definitive diagnosis.
• Magnetic resonance imaging and immunoblot analyses in rats with experimentally induced cerebral alveolar echinococcosis

  T Asanuma, Y Matsumoto, M Takiguchi, O Inanami, M Nakao, K Nakaya, A Ito, A Hashimoto, M Kuwabara

  COMPARATIVE MEDICINE 53 6 649 - 656 2003年12月 [査読有り][通常論文]
   

  The early stage of experimentally induced secondary cerebral alveolar echinococcosis (AE) in rats was investigated by use of magnetic resonance imaging (MRI) and immunoblot (western blot) analyses. Thirty-six female Wistar rats (6 to 8 weeks old) were injected intracranially with a 10% homogenate of echinococcal larval tissues in which the concentrations of microvesicles and protoscolices were estimated to be 3.8 and 1.5 x 10(4)/ml, respectively. To observe the fine structure of the rat brain, MRI was performed under a high magnetic field of 7.05 T. Histologic examination also was performed. The T2-weighted MR images revealed a hyperintense region in the cerebral cortex at two weeks after injection of the homogenate. At three weeks after injection, this region was found to have cysts on the basis of results of histologic examination. Signal-void regions corresponding to hyperplasia and the subsequent calcification of the cuticle layer at six and 13 weeks after injection, respectively, were observed in T2-weighted and proton density MR images. On the other hand, at nine weeks after injection, AE was discernible by use of western blot analysis of sera with antibodies of two epitopes (Em18 and Em16) of E. multilocularis. Using this secondary cerebral AE animal model, it was concluded that the MRI method was suitable for early detection of secondary cerebral AE.
• Presence of B7-2+ dendritic cells and expression of Th1 cytokines in the early development of sialodacryoadenitis in the IqI/Jic mouse model of primary Sjörgren's syndrome.

  Konno A, Takada K, Saegusa J, Takiguchi M

  Autoimmunity 36 4 247 - 254 2003年06月 [査読有り][通常論文]
   

  Subpopulations of infiltrating lymphocytes, professional antigen-presenting cells (APCs), and Th1/Th2 cytokines that could initiate an autoimmune sialodacryoadenitis were studied in the IQI/Jic mouse model of primary Sjogren's syndrome. Although lymphocytic infiltrations were first seen in submandibular glands (SMGs) of females and in lacrimal glands (LGs) of males at 8 weeks of age, clusters of MHC class II+, GD11c+, B7-2+ dendritic cells (DCs) were already localized in these tissues at 4 weeks. At 8 weeks, the infiltrating lymphocytes consisted of almost equal numbers of B cells and CD4+ T cells. In the inflammatory foci, MHC class II+, CD11c+, B7-2+ DCs formed network-like structures. Duct cells in the lesions showed immunoreactivities for MHC class II and ALCAM (a costimulatory adhesion molecule). IL-12 and IFN-γ transcripts were detected by RT-PCR in SMGs of females and in LGs of males at 8-12 weeks. These results suggest that the clustered DCs might play an important role in the initiation of the adenitis, and further suggest that the DCs and epithelial cells may participate in the activation of CD4+ T cells. It is also likely that Th1 cytokines mediate the functional interactions between the APCs and CD4+ T cells in the early lesions.
• Virologic and serologic identification of minute virus of canines (canine parvovirus type 1) from dogs in Japan

  M Mochizuki, M Hashimoto, T Hajima, M Takiguchi, A Hashimoto, Y Une, F Roerink, T Ohshima, CR Parrish, LE Carmichael

  JOURNAL OF CLINICAL MICROBIOLOGY 40 11 3993 - 3998 2002年11月 [査読有り][通常論文]
   

  Minute virus of canines (MVC), also known as canine parvovirus type 1, was initially believed to be a nonpathogenic agent, since it was first isolated from canine fecal specimens in the late 1960s. However, subsequent pathological as well as epidemiological studies suggested that MVC is a pathogen of neonatal puppies and is widely distributed among domestic dogs in the United States. The virus also has been shown to cause fetal deaths. Nevertheless, the virus was not detected in dogs outside the United States until recently, presumably because of a lack of widespread availability of the only susceptible canine cell line, WRCC/3873D, used for MVC isolation. We examined 470 clinical specimens from 346 dogs by PCR and detected MVC-specific gene fragments from four diseased puppies (positive rate, 1.2%). Viruses were recovered from three PCR-positive rectal specimens by using WRCC/3873D and MDCK cells. The isolates possessed antigenic and genomic properties similar to those of the U.S. reference strain GA3 and were identified as MVC. In addition, seroepidemiological evidence that 5.0% of dogs possessed anti-MVC antibodies also indicated the presence of MVC infection among dogs in Japan. From this study and several recent European reports describing MVC field cases, it is evident that MVC is distributed among domestic dogs worldwide.
• Detection of Canine Herpesvirus DNA in the Ganglionic Neurons and the Lymph Node Lymphocytes of Latently Infected Dogs

  Masahiro Miyoshi, Yuki Ishii, Mitsuyoshi Takiguchi, Ayato Takada, Jun Yasuda, Akira Hashimoto, Katsunori Okazaki, Hiroshi Kida

  Journal of Veterinary Medical Science 61 4 375 - 379 1999年04月 [査読有り][通常論文]
   

  To determine the site of latent infection of canine herpesvirus (CHV), tissues from dogs convalescent from acute infection with CHV were examined for the presence of viral genome DNA by the nested polymerase chain reaction. CHV DNA was detected in the trigeminal ganglia and the retropharyngeal lymph nodes. In situ hybridization study of the tissues revealed that CHV genome persisted in the nuclei of ganglionic neurons and lymphocytes.
• イヌヘルペスウイルスの神経節神経細胞及びリンパ節リンパ球における潜伏感染

  三好 正浩, 石井 由紀, 滝口 満喜, 高田 礼人, 安田 隼, 橋本 晃, 岡崎 克則, 喜田 宏

  The Journal of Veterinary Medical Science 61 4 375 - 379 1999年04月 [査読有り][通常論文]
  

MISC

• 乳び胸の原因としてリンパ管腫症が疑われた犬の1例

  早坂 郁人, 新坊 弦也, 細谷 謙次, 三木 伸悟, 滝口 満喜 日本獣医画像診断学会抄録 73回 np176 -np176 2023年12月
• 犬の腎うっ血の評価におけるShear wave elastographyの有用性の検討

  塩原 希, 中村 健介, 横山 望, 森下 啓太郎, 滝口 満喜 北海道獣医師会雑誌 67 (8) 316 -316 2023年08月
• 拘束型心筋症に伴う左室内血栓により大動脈血栓塞栓に陥った猫の1例

  立花 圭, 中村 健介, 塩原 希, 川上 侑記, 滝口 満喜 北海道獣医師会雑誌 67 (8) 318 -318 2023年08月
• コンパニオンアニマルのPFAS汚染:イヌ・ネコの種差要因と汚染の地域差

  佐藤 愛佳, 佐藤 楓夏, 水川 葉月, 池中 良徳, 田上 瑠美, 横山 望, 滝口 満喜, 中津 賞, 野見山 桂 環境化学物質3学会合同大会要旨集 2回 305 -306 2023年05月
• 胃・小腸の拡張—特集 画像所見からみる診断のアプローチ

  横山 望, 滝口 満喜 伴侶動物画像診断 = Diagnostic imaging of companion animal 8 (2) 6 -32 2023年04月
• 造影超音波検査で副腎皮質の血流消失を確認した医原性副腎皮質機能低下症の犬の1例

  永田矩之, 前田貞俊, 青島圭佑, 中村健介, 滝口満喜 日本産業動物獣医学会(中部)・日本小動物獣医学会(中部)・日本獣医公衆衛生学会(中部) 2023 2023年
• 犬の発作性ジスキネジア23例の回顧的検討

  川上侑記, 笹岡一慶, 大田寛, 山根由久, 新坊弦也, 横山望, 佐々木東, 森下啓太郎, 中村健介, 滝口満喜 北海道獣医師会雑誌 67 (8) 2023年
• 犬尿路上皮癌におけるPDXモデルの樹立

  森下 大暉, 木之下 怜平, 青島 圭佑, 細谷 謙次, 山崎 淳平, 滝口 満喜 日本獣医学会学術集会講演要旨集 165回 [B2P -03] 2022年09月
• 容量過負荷状態の犬における心エコー図法による左心房stiffnessの推定

  大菅 辰幸, 田村 昌大, 佐々木 東, 滝口 満喜 日本獣医学会学術集会講演要旨集 165回 [HS1P -05] 2022年09月
• 2次診療動物病院に来院した犬の糞便真核生物叢解析

  横山 望, 川口 剛, 中尾 亮, 森下 啓太郎, 細谷 謙次, 永田 矩之, 笹岡 一慶, 新坊 弦也, 佐々木 東, 中村 健介, 滝口 満喜 日本獣医学会学術集会講演要旨集 165回 [HS1P -16] 2022年09月
• 犬尿路上皮癌におけるPDXモデルの樹立

  森下 大暉, 木之下 怜平, 青島 圭佑, 細谷 謙次, 山崎 淳平, 滝口 満喜 日本獣医学会学術集会講演要旨集 165回 [B2P -03] 2022年09月
• 低コレステロール血症は犬の膵外分泌不全を予測できるのか?

  横山 望, 大田 寛, 永田 矩之, 笹岡 一慶, 新坊 弦也, 佐々木 東, 森下 啓太郎, 中村 健介, 滝口 満喜 北海道獣医師会雑誌 66 (8) 284 -284 2022年08月
• 洞停止を認めた咳嗽失神の犬の1例

  幸野 瑠美, 中村 健介, 笹岡 一慶, 塩原 希, 小幡 祐路, 滝口 満喜 北海道獣医師会雑誌 66 (8) 284 -284 2022年08月
• 不完全型房室中隔欠損症の外科的整復時に両側房室弁の弁輪形成術を行った犬の1例

  川元 誠, 中村 健介, 森 拓也, 古越 真耶, 大橋 美里, 三木 悠矢, 森下 啓太郎, 滝口 満喜 北海道獣医師会雑誌 66 (8) 285 -285 2022年08月
• 甲状腺機能低下症の治療により失神の消失を認めた犬の1例

  塩原 希, 中村 健介, 幸野 瑠美, 滝口 満喜 北海道獣医師会雑誌 66 (8) 285 -285 2022年08月
• 臨床的に間質性肺疾患と診断された犬25頭の回顧的検討

  川上 侑記, 中村 健介, 新坊 弦也, 山根 由久, 大菅 辰幸, 竹内 恭介, 木之下 怜平, 細谷 謙次, 永田 矩之, 滝口 満喜 北海道獣医師会雑誌 66 (8) 286 -286 2022年08月
• 犬尿中コルチゾール/クレアチニン比の基準値の確立とクッシング症候群の診断への応用

  永田 矩之, 澤村 飛龍, 五日市 大介, 森下 啓太郎, 細谷 謙次, 横山 望, 笹岡 一慶, 佐々木 東, 中村 健介, 池中 良徳, 滝口 満喜 北海道獣医師会雑誌 66 (8) 286 -286 2022年08月
• 院内湿潤環境に対する注意喚起 北大附属動物病院における環境サーベイランス結果

  笹岡 一慶, 新田 優里香, 佐藤 豊孝, 堀内 基広, 滝口 満喜 北海道獣医師会雑誌 66 (8) 287 -287 2022年08月
• 磁気共鳴スペクトロスコピーは犬の起源不明髄膜脳脊髄炎の予後指標となり得るか

  山口 敬央, 笹岡 一慶, 新坊 弦也, 山根 由久, 永田 矩之, 横山 望, 森下 啓太郎, 佐々木 東, 中村 健介, 滝口 満喜 北海道獣医師会雑誌 66 (8) 287 -287 2022年08月
• 造影CT検査後に非心原性肺水腫を呈した褐色細胞腫を疑う犬の1例

  吉田 紫乃, 田村 純, 永田 矩之, 大山 紀彦, 新坊 弦也, 池中 良徳, 滝口 満喜 北海道獣医師会雑誌 66 (8) 289 -289 2022年08月
• 麻酔中パルスオキシメーター測定異常から舌局所の灌流障害を疑った犬の1例

  田村 純, 湯本 優希, 大山 紀彦, 新坊 弦也, 滝口 満喜 北海道獣医師会雑誌 66 (8) 289 -289 2022年08月
• 日本のペット動物における有機フッ素化合物の汚染実態

  野見山 桂, 佐藤 楓夏, 水川 葉月, 池中 良徳, 田上 瑠美, 横山 望, 滝口 満喜 環境化学物質3学会合同大会要旨集 2022年 195 -196 2022年06月
• 「新型コロナ感染症(COVID-19)下での参加型臨床実習の実施 2020年度北海道大学動物医療センターにおける参加型臨床実習の実際

  滝口 満喜 日本獣医学会学術集会講演要旨集 164回 [HSS -2] 2021年09月
• メタボロミクスおよび甲状腺ホルモン分析による有機ハロゲン汚染物質への曝露によって引き起こされたペット猫(Felis silvestris catus)の健康影響評価

  野見山 桂, 山本 恭央, 江口 哲史, 西川 博之, 水川 葉月, 横山 望, 市居 修, 滝口 満喜, 中山 翔太, 池中 良徳, 石塚 真由美, 国末 達也 環境ホルモン学会研究発表会要旨集 23回 55 -55 2021年09月
• 「新型コロナ感染症(COVID-19)下での参加型臨床実習の実施 2020年度北海道大学動物医療センターにおける参加型臨床実習の実際

  滝口 満喜 日本獣医学会学術集会講演要旨集 164回 [HSS -2] 2021年09月
• 犬の僧帽弁疾患における2D Speckle Tracking心エコー図法により推定した左心房stiffnessと予後の関係

  大菅 辰幸, 黒田 杏子, 森田 智也, 中村 健介, 佐々木 東, 滝口 満喜 日本獣医学会学術集会講演要旨集 164回 [HSO -8] 2021年09月
• Comprehensive analysis of steroid profile in dogs with Cushing' syndrome and hepatocellular carcinoma(和訳中)

  Oo Thandar, 佐々木 東, 池中 良徳, 永田 矩之, 一瀬 貴大, Bin Teoh Yong, 川元 誠, 小島 一輝, 菅原 芽伊, 中山 翔太, 石塚 真由美, 中村 健介, 滝口 満喜 日本獣医学会学術集会講演要旨集 164回 [HSO -18] 2021年09月
• イヌの肝細胞腫瘍におけるDNAメチル化の網羅的解析

  淺利 友, 山崎 淳平, Oo Thander, 細谷 謙次, 金 尚昊, 木之下 怜平, 竹内 恭介, 賀川 由美子, 佐々木 東, 中村 健介, 滝口 満喜 日本獣医学会学術集会講演要旨集 164回 [HSO -30] 2021年09月
• Identification of pathogenic Single Nucleotide Polymorphism in Inflammatory Colorectal Polyps of Miniature Dachshunds(和訳中)

  Bin Teoh Yong, 永田 矩之, 大田 寛, 佐々木 東, 中村 健介, 村上 正晃, 滝口 満喜 日本獣医学会学術集会講演要旨集 164回 [HSO -32] 2021年09月
• 非再生性免疫介在性貧血の犬における脾臓摘出術前後の血清中蛋白の網羅的解析

  菅原 芽伊, 山崎 淳平, 森下 啓太郎, 金 尚昊, 細谷 謙次, 佐々木 東, 中村 健介, 滝口 満喜 日本獣医学会学術集会講演要旨集 164回 [HSO -60] 2021年09月
• 重度肝線維化を伴う好酸球性肉芽腫を認めた好酸球増多症候群の若齢小型犬の1例

  篠原 正義, 田村 昌大, 金 尚昊, 賀川 由美子, 滝口 満喜 北海道獣医師会雑誌 65 (8) 262 -262 2021年08月
• 長期生存している特発性被嚢性腹膜硬化症の猫の1例

  前田 晴香, 横山 望, 木之下 怜平, 大田 寛, 岡田 一喜, 賀川 由美子, 滝口 満喜 北海道獣医師会雑誌 65 (8) 263 -263 2021年08月
• 左室壁肥厚と動的流出路閉塞を呈した犬の3例

  湯本 優希, 中村 健介, 志波 一恵, 寺澤 元子, 早坂 郁人, 滝口 満喜 北海道獣医師会雑誌 65 (8) 263 -263 2021年08月
• 重度肝線維化を伴う好酸球性肉芽腫を認めた好酸球増多症候群の若齢小型犬の１例

  篠原正義, 田村昌大, 金 尚昊, 賀川由美子, 滝口満喜 北海道獣医師会雑誌 65 (8) 46 -46 2021年08月
• 非造影4D-MRAにより診断した鎖骨下動脈盗血症候群の犬の1症例

  新坊弦也, 越後良介, 越後良介, 滝口満喜 北海道獣医師会雑誌 65 (8) 268 -268 2021年08月
• 超音波で生体の壁を超える 超音波と気泡を併用する膀胱内注入療法の犬における安全性検討

  佐々木 東, 青柳 貞一郎, 池中 良徳, 工藤 信樹, 中村 健介, 滝口 満喜 超音波医学 48 (Suppl.) S195 -S195 2021年04月
• 超音波で生体の壁を超える 超音波と気泡を併用する膀胱内注入療法の犬における安全性検討

  佐々木 東, 青柳 貞一郎, 池中 良徳, 工藤 信樹, 中村 健介, 滝口 満喜 超音波医学 48 (Suppl.) S195 -S195 2021年04月
• Smart Metabolite Databaseを用いたBDE209長期曝露試験によるネコ血清中メタボロームの変動解析

  野見山桂, 林多聞, 江口哲史, 水川葉月, 高口倖暉, 横山望, 市居修, 滝口満喜, 笹岡一慶, 中山翔太, 池中良徳, 石塚真由美, 国末達也 環境化学討論会要旨集(CD-ROM) 29th 2021年
• LC-MS/MSを用いたステロイドホルモンの一斉分析法による,副腎皮質機能亢進症(クッシング症候群)の病態解明について

  一瀬貴大, 安田淑一, 佐々木東, 滝口満喜, 中山翔太, 石塚真由美, 池中良徳 JSBMS Letters 46 (Supplement) 75 -75 2021年
• メラトニンの経口投与が著効した両側性副腎腫大を伴う全身性脱毛症のフェレットの1例

  BIN Teoh Yong, 亀山健吾, 永田矩之, 佐々木東, 中村健介, 滝口満喜 北海道獣医師会雑誌 65 (8) 265 -265 2021年
• 超音波と気泡を併用する膀胱内注入療法の犬における安全性検討

  佐々木東, 青柳貞一郎, 池中良徳, 工藤信樹, 中村健介, 滝口満喜 超音波医学 Supplement 48 2021年
• 診療力が試される症例 Vet Board QUIZ 肝・胆道系・膵外分泌 若齢で腹水を認めたボーダー・コリー

  田村 昌大, 滝口 満喜, 中村 健介 Veterinary Board 2 (12) 64 -69 2020年12月
• 最近の超音波による癌治療 その可能性と課題

  近藤 隆, 鈴木 亮, 佐々木 東, 滝口 満喜 Thermal Medicine 36 (3) 75 -90 2020年09月 

  超音波の作用は熱作用と非熱作用に大別され、非熱作用はキャビテーション作用と非キャビテーション作用に分けられる。以前、超音波による癌治療としては、1)超音波単独(主にハイパーサミア治療)、2)放射線治療との併用、および3)化学療法との併用があった。近年、超音波に関する生物学・基礎医学に関して、細胞死、遺伝子発現、遺伝子導入、化学物質との相互作用、薬物送達等の研究が進展してきた。とりわけ、微小気泡は診断のみならず治療のツールとして注目され、その研究は大きく発展してきた。臨床応用も集束超音波治療、低強度パルス波超音波治療、加えて血液-脳-関門の開口に関する技術の進展が著しい。本総説では、超音波による癌治療に関して、歴史的経緯を述べるとともに最近の熱作用および非熱作用を利用した癌治療についてその可能性と課題について考察する。(著者抄録)
• 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

  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 SA Medicine 22 (3) 74 -75 2020年06月
• イソフルラン麻酔下においてノルアドレナリンが全身循環に及ぼす影響

  小島 一輝, 石塚 友人, 佐藤 敬近, 滝口 満喜 日本獣医麻酔外科学雑誌 50 (Suppl.2) 285 -285 2019年12月
• Two-dimensional shear wave elastographyによる非侵襲的な犬の肝線維化診断

  田村 昌大, 大田 寛, 大菅 辰幸, 新坊 弦也, 佐々木 東, 森下 啓太郎, 賀川 由美子, 滝口 満喜 日本獣医麻酔外科学雑誌 50 (Suppl.2) 315 -315 2019年12月
• Two-dimensional shear wave elastographyによる非侵襲的な犬の肝線維化診断

  田村 昌大, 大田 寛, 大菅 辰幸, 新坊 弦也, 佐々木 東, 森下 啓太郎, 賀川 由美子, 滝口 満喜 日本獣医麻酔外科学雑誌 50 (Suppl.2) 315 -315 2019年12月 [査読無し][通常論文]
  
• LC‐MS/MSを用いたイヌ尿中メタネフリンおよびノルメタネフリン測定

  井上裕美子, 佐々木東, 池中良徳, 一瀬貴大, 笹岡一慶, 大菅辰幸, 中山翔太, 森下啓太郎, 大田寛, 石塚真由美, 滝口満喜 日本獣医学会学術集会講演要旨集 162nd 470 2019年08月20日 [査読無し][通常論文]
  
• LC‐MS/MS法を用いたイヌ血清中ステロイドホルモンの分析法の確立と内分泌疾患モデルを用いた実測

  白尾大樹, 池中良徳, 一瀬貴大, 中山翔太, 佐々木東, 永田矩之, 水川葉月, 滝口満喜, 石塚真由美 日本獣医学会学術集会講演要旨集 162nd 470 2019年08月20日 [査読無し][通常論文]
  
• 【部位別の基本描出シリーズ 循環器編(3)心臓 各論 後天性疾患】超音波検査

  大菅 辰幸, 滝口 満喜 伴侶動物画像診断 4 (4) 28 -71 2019年08月
• LC-MS/MSを用いたイヌ尿中メタネフリンおよびノルメタネフリン測定

  井上 裕美子, 佐々木 東, 池中 良徳, 一瀬 貴大, 笹岡 一慶, 大菅 辰幸, 中山 翔太, 森下 啓太郎, 大田 寛, 石塚 真由美, 滝口 満喜 日本獣医学会学術集会講演要旨集 162回 470 -470 2019年08月
• LC-MS/MS法を用いたイヌ血清中ステロイドホルモンの分析法の確立と内分泌疾患モデルを用いた実測

  白尾 大樹, 池中 良徳, 一瀬 貴大, 中山 翔太, 佐々木 東, 永田 矩之, 水川 葉月, 滝口 満喜, 石塚 真由美 日本獣医学会学術集会講演要旨集 162回 470 -470 2019年08月
• 北大附属動物病院における薬剤耐性モニタリング調査結果2018

  笹岡 一慶, 森下 啓太郎, 細谷 謙次, 滝口 満喜 北海道獣医師会雑誌 63 (8) 334 -334 2019年08月
• ネコのアクロメガリー関連インスリン抵抗性糖尿病のコントロールを目的とした成長ホルモン受容体/Fc融合タンパク質の作製

  鈴木 理紗, 和泉 雄介, 前川 直也, 今内 覚, 高木 哲, 森下 啓太郎, 細谷 謙次, 滝口 満喜 日本獣医学会学術集会講演要旨集 162回 469 -469 2019年08月
• 部位別の基本描出シリーズ 循環器編 3)心臓 各論 後天性心疾患

  大菅辰幸, 滝口満喜 伴侶動物画像診断 4 (4) 28 -71 2019年08月 [査読無し][招待有り]
  
• 詳細な病理学的解析に基づいて治療方針を決定した免疫複合体性糸球体腎炎の犬の1例

  新井田 篤, 大田 寛, 笹岡 一慶, 細谷 謙次, 市居 修, 賀川 由美子, 大菅 辰幸, 佐々木 東, 森下 啓太郎, 滝口 満喜 北海道獣医師会雑誌 63 (8) 336 -336 2019年08月 [査読無し][通常論文]
  
• 過去3年間の輸血後副反応に関する回顧的研究

  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 北海道獣医師会雑誌 63 (8) 337 -337 2019年08月 [査読無し][通常論文]
  
• 経皮的ドレナージで良好に経過した胃排出障害を伴う膵仮性嚢胞の犬の1例

  坂本 暁彦, 大田 寛, 杉浦 岳, 康井 翔平, 大菅 辰幸, 佐々木 東, 森下 啓太郎, 滝口 満喜 北海道獣医師会雑誌 63 (8) 341 -341 2019年08月 [査読無し][通常論文]
  
• 肝皮症候群を疑い血漿アミノ酸解析を行った肝硬変の犬の1例

  上條 太貴, 大田 寛, 賀川 由美子, 大菅 辰幸, 佐々木 東, 森下 啓太郎, 滝口 満喜 北海道獣医師会雑誌 63 (8) 341 -341 2019年08月 [査読無し][通常論文]
  
• 犬の先天性肝外門脈体循環シャントの術後合併症率と危険因子に関する回顧的研究

  鈴木 理紗, 細谷 謙次, 金 尚昊, 森下 啓太郎, 大田 寛, 滝口 満喜, 奥村 正裕 北海道獣医師会雑誌 63 (8) 349 -349 2019年08月 [査読無し][通常論文]
  
• 犬の僧帽弁疾患における2D Speckle Tracking心エコー図法を用いた左心房stiffnessの推定

  黒田 杏子, 大菅 辰幸, 笹岡 一慶, 森下 啓太郎, 佐々木 東, 大田 寛, 滝口 満喜 日本獣医学会学術集会講演要旨集 162回 464 -464 2019年08月 [査読無し][通常論文]
  
• 猫の新規炎症マーカー、ロイシンリッチα2糖蛋白質(LRG)の測定系構築の試み

  坂本 暁彦, 大田 寛, 好井 健太朗, 矢吹 悠久美, 笹岡 一慶, 大菅 辰幸, 佐々木 東, 森下 啓太郎, 滝口 満喜 日本獣医学会学術集会講演要旨集 162回 475 -475 2019年08月 [査読無し][通常論文]
  
• PCBs曝露によるネコ肝トランスクリプトームへの影響

  水川葉月, NGYUEN Hoa Thanh, 岩田久人, 野見山桂, 池中良徳, 中山翔太, 横山望, 市居修, 滝口満喜, KHIDKHAN Kraisiri, 田辺信介, 石塚真由美 環境化学討論会要旨集(CD-ROM) 28th ROMBUNNO.1C‐08 2019年06月11日 [査読無し][通常論文]
  
• デカブロモジフェニルエーテル(BDE209)の長期曝露がイエネコへ及ぼす影響

  田中啓介, 野見山桂, 水川葉月, 水川葉月, 高口倖暉, 田上瑠美, 横山望, 市居修, 滝口満喜, 笹岡一慶, 中山翔太, 池中良徳, 石塚真由美, 国末達也, 田辺信介 環境化学討論会要旨集(CD-ROM) 28th ROMBUNNO.1C‐09 2019年06月11日 [査読無し][通常論文]
  
• 【部位別の基本描出シリーズ 循環器編(2)心臓 各論 先天性疾患】超音波検査

  大菅 辰幸, 滝口 満喜 伴侶動物画像診断 4 (3) 24 -66 2019年06月
• 部位別の基本描出シリーズ 循環器編 2)心臓 各論 先天性心疾患

  大菅辰幸, 滝口満喜 伴侶動物画像診断 4 (3) 24 -66 2019年06月 [査読無し][招待有り]
  
• 慢性僧帽弁疾患犬において心室間流入時間差は有用な心機能評価指標である

  森田 智也, 中村 健介, 大菅 辰幸, 滝口 満喜 日本獣医麻酔外科学雑誌 50 (Suppl.1) 322 -322 2019年06月 [査読無し][通常論文]
  
• 閉塞性黄疸はShear Wave Elastographyによる肝硬度測定に影響を与える

  田村 昌大, 大田 寛, 新坊 弦也, 大菅 辰幸, 佐々木 東, 森下 啓太郎, 滝口 満喜 日本獣医麻酔外科学雑誌 50 (Suppl.1) 333 -333 2019年06月 [査読無し][通常論文]
  
• 大学動物病院の活動の現状とさらなる発展を目指して 北海道大学動物医療センターの取組みと課題

  滝口 満喜 日本獣医師会雑誌 72 (5) 240 -242 2019年05月
• 蚕白喪失性腸症の犬40例からの腸リンパ管拡張症の診断と治療に関する考察

  永田 矩之, 大田 寛, 横山 望, 佐々木 東, 大菅 辰幸, 森下 啓太郎, 滝口 満喜 日本獣医師会雑誌 72 (4) 234 -235 2019年04月
• 【部位別の基本描出シリーズ 循環器編(1) 心臓 総論】超音波検査

  大菅 辰幸, 滝口 満喜 伴侶動物画像診断 4 (2) 27 -68 2019年04月
• 部位別の基本描出シリーズ 循環器編 1)心臓 総論 超音波検査

  大菅辰幸, 滝口満喜 伴侶動物画像診断 4 (2) 27 -68 2019年04月 [査読無し][招待有り]
  
• 蚕白喪失性腸症の犬40例からの腸リンパ管拡張症の診断と治療に関する考察

  永田 矩之, 大田 寛, 横山 望, 佐々木 東, 大菅 辰幸, 森下 啓太郎, 滝口 満喜 日本獣医師会雑誌 72 (4) 234 -235 2019年04月 [査読無し][通常論文]
  
• 低強度パルス超音波照射による毛髪細胞刺激

  佐々木 東, 工藤 信樹, 大田 寛, 滝口 満喜 超音波医学 46 (Suppl.) S579 -S579 2019年04月 [査読無し][通常論文]
  
• 蛋白喪失性腸症の犬40例からの腸リンパ管拡張症の診断と治療に関する考察

  永田矩之, 大田寛, 横山望, 佐々木東, 大菅辰幸, 森下啓太郎, 滝口満喜 日本獣医師会獣医学術学会年次大会講演要旨集 2018 2019年
• 慢性僧帽弁疾患犬において心室間流入時間差は有用な心機能評価指標である

  森田智也, 中村健介, 大菅辰幸, 大菅辰幸, 滝口満喜 日本獣医麻酔外科学雑誌(Web) 50 (Supplement 1) 2019年
• ピモベンダンは慢性塞栓性肺高血圧症において圧を上げずに拍出量を上げる

  森田 智也, 中村 健介, 大菅 辰幸, 滝口 満喜 日本獣医麻酔外科学雑誌 49 (Suppl.2) 242 -242 2018年12月 [査読無し][通常論文]
  
• 犬の僧帽弁疾患における心エコー図法により推定した左心室-動脈カップリングとステージの関係

  大菅 辰幸, 森田 智也, 佐々木 東, 森下 啓太郎, 大田 寛, 滝口 満喜 日本獣医麻酔外科学雑誌 49 (Suppl.2) 249 -249 2018年12月 [査読無し][通常論文]
  
• Shear Wave Elastographyによる犬の肝硬度評価の試み

  田村 昌大, 森下 啓太郎, 新坊 弦也, 佐々木 東, 大田 寛, 滝口 満喜 日本獣医画像診断学会抄録 64回 13 -13 2018年11月
• やっぱり難しい膵炎診断 症状、膵リパーゼ、画像をどう評価するか? 膵炎の画像診断を中心に

  滝口 満喜 動物臨床医学会年次大会プロシーディング 39回 (1) 77 -77 2018年11月
• 超音波造影を含めた超音波検査の将来

  滝口 満喜 日本獣医画像診断学会抄録 64回 9 -9 2018年11月
• Shear Wave Elastographyによる犬の肝硬度評価の試み

  田村 昌大, 森下 啓太郎, 新坊 弦也, 佐々木 東, 大田 寛, 滝口 満喜 日本獣医画像診断学会抄録 64回 13 -13 2018年11月 [査読無し][通常論文]
  
• 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 62 (8) 334 2018年08月24日 [査読無し][通常論文]
  
• シスプラチン膀胱内ソノポレーションの前臨床試験的検討

  佐々木東, 中山翔太, 大田寛, 大菅辰幸, 森下啓太郎, 水川葉月, 池中良徳, 石塚真由美, 滝口満喜 日本獣医学会学術集会講演要旨集 161st 429 2018年08月21日 [査読無し][通常論文]
  
• 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 62 (8) 334 -334 2018年08月
• シスプラチン膀胱内ソノポレーションの前臨床試験的検討

  佐々木 東, 中山 翔太, 大田 寛, 大菅 辰幸, 森下 啓太郎, 水川 葉月, 池中 良徳, 石塚 真由美, 滝口 満喜 日本獣医学会学術集会講演要旨集 161回 429 -429 2018年08月
• 術前からダイナミックな血圧変動を呈した褐色細胞腫を良好に麻酔管理した犬の1例

  小島 一輝, 石塚 友人, 金 尚昊, 竹内 恭介, 細谷 謙次, 滝口 満喜, 奥村 正裕 北海道獣医師会雑誌 62 (8) 336 -336 2018年08月
• 蛋白喪失性腸症の犬33例からの腸リンパ管拡張症の診断と治療に関する考察

  永田 矩之, 大田 寛, 横山 望, ニサ・ホイルン, 佐々木 東, 森下 啓太郎, 滝口 満喜 北海道獣医師会雑誌 62 (8) 334 -334 2018年08月 [査読無し][通常論文]
  
• 神経筋接合部検査としてアイスパックテストを試みた重症筋無力症の犬の1例

  山田 有紗, 笹岡 一慶, 大田 寛, 立花 由莉加, 大菅 辰幸, 佐々木 東, 森下 啓太郎, 滝口 満喜 北海道獣医師会雑誌 62 (8) 335 -335 2018年08月 [査読無し][通常論文]
  
• 犬の粘液腫様変性性僧帽弁疾患における心エコー図法による左心室-大動脈カップリングの推定

  大菅 辰幸, 佐々木 東, 森下 啓太郎, 大田 寛, 滝口 満喜 北海道獣医師会雑誌 62 (8) 335 -335 2018年08月 [査読無し][通常論文]
  
• 神経症状を主訴とした悪性中皮腫の猫の1例

  大村 侑己, 大田 寛, 小林 篤史, 笹岡 一慶, 道下 明日香, 大菅 辰幸, 佐々木 東, 森下 啓太郎, 滝口 満喜 北海道獣医師会雑誌 62 (8) 340 -340 2018年08月 [査読無し][通常論文]
  
• 経頭蓋超音波ドプラ法により局所的な脳循環動態を評価し得た右中大脳動脈梗塞の犬の1例

  笹岡 一慶, 大田 寛, 石塚 友人, 大菅 辰幸, 立花 由莉加, 森下 啓太郎, 佐々木 東, 滝口 満喜 北海道獣医師会雑誌 62 (8) 341 -341 2018年08月 [査読無し][通常論文]
  
• 鼻腔内真菌感染症に対しクロトリマゾール灌流および注入療法を実施した犬の1例

  大谷 豪, 大田 寛, 岩木 有香, 細谷 謙次, 新坊 弦也, 佐々木 東, 森下 啓太郎, 滝口 満喜 北海道獣医師会雑誌 62 (8) 344 -344 2018年08月 [査読無し][通常論文]
  
• 健康な犬における二次元スペックルトラッキング心エコーによる左心室長軸方向ストレイン解析に与える心臓容積負荷の影響(Effect of cardiac volume loading on left atrial longitudinal strain analysis derived from two-dimensional Speckle Tracking Echocardiography in healthy dogs)

  Dermlim Angkhana, 中村 健介, 森田 智也, 大菅 辰幸, Nisa Khoirun, Leela-arporn Rommaneeya, 笹岡 一慶, 永田 矩之, 田村 昌大, 佐々木 東, 大田 寛, 森下 啓太郎, 滝口 満喜 日本獣医学会学術集会講演要旨集 161回 435 -435 2018年08月 [査読無し][通常論文]
  
• 蛋白喪失性腸症の犬33例からの腸リンパ管拡張症の診断と治療に関する考察

  永田 矩之, 大田 寛, 横山 望, ニサ・ホイルン, 佐々木 東, 森下 啓太郎, 滝口 満喜 北海道獣医師会雑誌 62 (8) 334 -334 2018年08月 [査読無し][通常論文]
  
• 神経筋接合部検査としてアイスパックテストを試みた重症筋無力症の犬の1例

  山田 有紗, 笹岡 一慶, 大田 寛, 立花 由莉加, 大菅 辰幸, 佐々木 東, 森下 啓太郎, 滝口 満喜 北海道獣医師会雑誌 62 (8) 335 -335 2018年08月 [査読無し][通常論文]
  
• 経頭蓋超音波ドプラ法により局所的な脳循環動態を評価し得た右中大脳動脈梗塞の犬の1例

  笹岡 一慶, 大田 寛, 石塚 友人, 大菅 辰幸, 立花 由莉加, 森下 啓太郎, 佐々木 東, 滝口 満喜 北海道獣医師会雑誌 62 (8) 341 -341 2018年08月 [査読無し][通常論文]
  
• 神経症状を主訴とした悪性中皮腫の猫の1例

  大村 侑己, 大田 寛, 小林 篤史, 笹岡 一慶, 道下 明日香, 大菅 辰幸, 佐々木 東, 森下 啓太郎, 滝口 満喜 北海道獣医師会雑誌 62 (8) 340 -340 2018年08月 [査読無し][通常論文]
  
• 犬の粘液腫様変性性僧帽弁疾患における心エコー図法による左心室-大動脈カップリングの推定

  大菅 辰幸, 佐々木 東, 森下 啓太郎, 大田 寛, 滝口 満喜 北海道獣医師会雑誌 62 (8) 335 -335 2018年08月 [査読無し][通常論文]
  
• 鼻腔内真菌感染症に対しクロトリマゾール灌流および注入療法を実施した犬の1例

  大谷 豪, 大田 寛, 岩木 有香, 細谷 謙次, 新坊 弦也, 佐々木 東, 森下 啓太郎, 滝口 満喜 北海道獣医師会雑誌 62 (8) 344 -344 2018年08月 [査読無し][通常論文]
  
• 術前からダイナミックな血圧変動を呈した褐色細胞腫を良好に麻酔管理した犬の1例

  小島 一輝, 石塚 友人, 金 尚昊, 竹内 恭介, 細谷 謙次, 滝口 満喜, 奥村 正裕 北海道獣医師会雑誌 62 (8) 336 -336 2018年08月 [査読無し][通常論文]
  
• Shear Wave Elastography(SWE)を用いた犬の肝硬度測定

  田村 昌大, 大田 寛, 佐々木 東, 賀川 由美子, 滝口 満喜 獣医畜産新報 71 (7) 496 -497 2018年07月 [査読無し][通常論文]
  
• Shear Wave Elastography(SWE)を用いた犬の肝硬度測定

  田村 昌大, 大田 寛, 佐々木 東, 賀川 由美子, 滝口 満喜 獣医畜産新報 71 (7) 496 -497 2018年07月 [査読無し][通常論文]
  
• 慢性僧帽弁疾患犬において右室strainによる右心室機能評価は優れた予後指標となり得るか

  森田 智也, 中村 健介, 大菅 辰幸, 森下 啓太郎, 佐々木 東, 大田 寛, 滝口 満喜 SA Medicine 20 (3) 68 -70 2018年06月
• ポリ塩化ビフェニル曝露によるイヌ・ネコの甲状腺ホルモン恒常性への影響

  高口 倖暉, 野見山 桂, 西川 博之, 水川 葉月, 田上 瑠美, 草木 桃子, 横山 望, 市居 修, 滝口 満喜, 中山 翔太, 池中 良徳, 石塚 真由美, 岩田 久人, 国末 達也, 田辺 信介 The Journal of Toxicological Sciences 43 (Suppl.) S245 -S245 2018年06月
• 肺塞栓症において認められる心室中隔の奇異性運動は左右心室間同期障害によって生じる

  中村 健介, 森田 智也, 大菅 辰幸, 池田 正悟, 三木 伸悟, Dermlim Angkhana, 滝口 満喜 日本獣医麻酔外科学雑誌 49 (Suppl.1) 301 -301 2018年06月 [査読無し][通常論文]
  
• 慢性僧帽弁疾患犬において右室strainによる右心室機能評価は優れた予後指標となり得るか

  森田智也, 中村健介, 大菅辰幸, 森下啓太郎, 佐々木東, 大田寛, 滝口満喜 SA Medicine 20 (3) 68‐70 2018年06月01日 [査読無し][通常論文]
  
• 有機ハロゲン化合物曝露によるネコの生化学マーカーの変化および甲状腺機能に及ぼす影響評価

  水川葉月, KHIDKHAN Kraisiri, 高口倖暉, 横山望, 市居修, 滝口満喜, 笹岡一慶, 池中良徳, 池中良徳, 中山翔太, TSEND‐AYUSH Sainnoxoi, 野見山桂, 田辺信介, 石塚真由美 環境化学討論会要旨集(CD-ROM) 27th ROMBUNNO.2A‐10 2018年05月11日 [査読無し][通常論文]
  
• ネコのin vivo BDE209長期曝露試験による体内動態の解明および甲状腺ホルモンへの影響評価

  田中啓介, 野見山桂, 水川葉月, 高口倖暉, 田上瑠美, 横山望, 市居修, 滝口満喜, 笹岡一慶, 中山翔太, 池中良徳, 石塚真由美, 国末達也, 田辺信介 環境化学討論会要旨集(CD-ROM) 27th ROMBUNNO.1A‐03(PA‐13) 2018年05月11日 [査読無し][通常論文]
  
• 犬の蛋白漏出性腸症の予後因子解析 超音波検査所見の有用性の検討

  大田 寛, 賀川 由美子, 大菅 辰幸, 佐々木 東, 森下 啓太郎, 滝口 満喜 日本獣医師会雑誌 71 (4) 206 -207 2018年04月
• 【部位別の基本描出シリーズ 内分泌器官編 甲状腺・上皮小体】超音波検査

  滝口 満喜 伴侶動物画像診断 3 (2) 54 -62 2018年04月
• ロジカルに修得する超音波検査(第1回) 総論 超音波診断装置とその調整

  滝口 満喜 伴侶動物画像診断 3 (2) 98 -101 2018年04月
• 犬の蛋白漏出性腸症の予後因子解析 超音波検査所見の有用性の検討

  大田 寛, 賀川 由美子, 大菅 辰幸, 佐々木 東, 森下 啓太郎, 滝口 満喜 日本獣医師会雑誌 71 (4) 206 -207 2018年04月 [査読無し][通常論文]
  
• 低強度パルス超音波による神経軸索の伸展制御の試み

  佐々木 東, 工藤 信樹, 大田 寛, 滝口 満喜 超音波医学 45 (Suppl.) S575 -S575 2018年04月 [査読無し][通常論文]
  
• 血清中メタボローム解析によるペットネコ(Felis catus)の有機ハロゲン化合物毒性影響評価

  野見山桂, 江口哲史, 西川博之, 水川葉月, 山本恭央, 滝口満喜, 中山翔太, 池中良徳, 石塚真由美, 田辺信介 環境化学討論会要旨集(CD-ROM) 27th 2018年
• JCVIM 2018 臨床研究アワード 慢性僧帽弁疾患犬において右室strainによる右心室機能評価は優れた予後指標となり得るか (第14回日本獣医内科学アカデミー学術大会(JCVIM 2018) 〈臨床研究アワード〉日本獣医内科学アカデミー/インターズー学術奨励賞受賞作品ダイジェスト版)

  森田 智也, 中村 健介, 大菅 辰幸, 森下 啓太郎, 佐々木 東, 大田 寛, 滝口 満喜 SA medicine : Journal of small animal medicine 24 (3) 68 -70 2018年 [査読無し][通常論文]
  
• ポリ塩化ビフェニル曝露によるイヌ・ネコの甲状腺ホルモン恒常性への影響

  高口 倖暉, 中山 翔太, 池中 良徳, 石塚 真由美, 岩田 久人, 国末 達也, 田辺 信介, 野見山 桂, 西川 博之, 水川 葉月, 田上 瑠美, 草木 桃子, 横山 望, 市居 修, 滝口 満喜 日本毒性学会学術年会 45 (0) P -72 2018年 [査読無し][通常論文]
   

  <p> 近年、ペット動物に対するポリ塩化ビフェニル（PCBs）および水酸化代謝物（OH-PCBs）の曝露による甲状腺ホルモン（THs）の恒常性への影響が注目されている。本研究ではPCBs曝露がペット動物のTHs恒常性に及ぼす影響を明らかにするため、イヌ・ネコのPCBs投与試験を実施し、PCBs曝露に伴う血清中THs濃度の変化を解析した。</p><p> PCBs投与後から5日間、継続的に血清を採取し、THs濃度の変化を解析した結果、ネコ血清中THs濃度は、総THs、遊離型THsともに対照群と投与群の間に有意な変化は認められなかった。一方、イヌ血清中総THs濃度は投与群において、総L-サイロキシン（T4）と総3,5,3'-トリヨード-L-サイロニン（T3）の減少傾向がみられ、総PCBs濃度は総T4、総T3濃度と有意な負の相関を示した（p < 0.01）。一方、遊離型T4、遊離型T3濃度では、対照群と投与群の間に経時的な変化は認められなかったが、曝露後48、96時間目で有意に増加した（p < 0.05）。加えて、遊離型T4濃度は総OH-PCBs濃度と正の相関を示し（p < 0.01）、異性体別ではT4様構造の高塩素化OH-PCBsで同様の傾向が認められた。上記の結果および先行研究から、PCBs曝露によるイヌ血清中THsへの影響を推察した。PCBsがT4様構造のOH-PCBsへ代謝されてTHs輸送タンパクに競合結合し、結合できない遊離型T4が血中に増加することで、THsの臓器・組織への取り込み量が増加したと予測される。その結果、イヌ肝臓中のTHs濃度は増加し、PCBs曝露により肝臓中のAhR・CARが過剰に誘導されることで、UGTおよびSULTが誘導され、THsの抱合化を促進することで体外排泄量が増加し、血清中総T4、T3が減少したものと推察された。</p>
• 内分泌性脱毛症の2例

  島崎 博美, 飯田 大起, 佐々木 東, 滝口 満喜, 藤井 義晴 (一社)比較統合医療学会学術大会・日本補完代替医療学会学術集会プログラム・抄録集 60回・20回 57 -58 2017年12月
• ポリ塩化ビフェニル(PCBs)がネコの甲状腺機能に及ぼす影響

  水川 葉月, 高居 名菜, 野見山 桂, 高口 倖暉, 横山 望, 市居 修, 滝口 満喜, 池中 良徳, 中山 翔太, 石塚 真由美 環境ホルモン学会研究発表会要旨集 20回 78 -78 2017年12月
• ポリ塩化ビフェニル(PCBs)がネコの甲状腺機能に及ぼす影響

  水川葉月, 高居名菜, 野見山桂, 高口倖暉, 横山望, 市居修, 滝口満喜, 池中良徳, 池中良徳, 中山翔太, 石塚真由美 日本内分泌かく乱化学物質学会研究発表会要旨集 20th 78 -78 2017年12月 [査読無し][通常論文]
  
• 消化管エコーのノウハウ

  滝口 満喜 動物臨床医学会年次大会プロシーディング 38回 (1) 91 -91 2017年11月
• すぐに診療で活かせる超音波画像診断の臨床

  滝口 満喜 動物臨床医学会年次大会プロシーディング 38回 (3) 205 -205 2017年11月
• 生前診断に苦慮した化膿性腸炎の猫の1例

  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 62回 6 -6 2017年09月
• 生前診断に苦慮した化膿性腸炎の猫の1例

  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) 62nd 6 (WEB ONLY) 2017年09月 [査読無し][通常論文]
  
• 超音波と膀胱内注入療法を組み合わせた膀胱癌治療法の開発

  佐々木東, 中山翔太, 森下啓太郎, 中村健介, 大田寛, 水川葉月, 池中良徳, 石塚真由美, 滝口満喜 日本獣医学会学術集会講演要旨集 160th 461 2017年08月30日 [査読無し][通常論文]
  
• 犬の右肝区域におけるCT画像解析を用いた静脈血管走行の多様性調査

  西野綾乃, 華園究, 石塚友人, 星野有希, 森下啓太郎, 滝口満喜, 高木哲 日本獣医学会学術集会講演要旨集 160th 455 2017年08月30日 [査読無し][通常論文]
  
• 犬の右肝区域におけるCT画像解析を用いた静脈血管走行の多様性調査

  西野 綾乃, 華園 究, 石塚 友人, 星野 有希, 森下 啓太郎, 滝口 満喜, 高木 哲 日本獣医学会学術集会講演要旨集 160回 455 -455 2017年08月
• 超音波と膀胱内注入療法を組み合わせた膀胱癌治療法の開発

  佐々木 東, 中山 翔太, 森下 啓太郎, 中村 健介, 大田 寛, 水川 葉月, 池中 良徳, 石塚 真由美, 滝口 満喜 日本獣医学会学術集会講演要旨集 160回 461 -461 2017年08月
• 造影超音波検査により計測する肺通過時間は肺動脈塞栓モデル犬において短縮する

  中村 健介, 森田 智也, 大菅 辰幸, 滝口 満喜 日本獣医学会学術集会講演要旨集 160回 465 -465 2017年08月 [査読無し][通常論文]
  
• 副腎偶発腫から診断した犬のサブクリニカルクッシング症候群の臨床的特徴

  永田 矩之, 大田 寛, 佐々木 東, 森下 啓太郎, 中村 健介, 細谷 謙次, 高木 哲, 滝口 満喜 北海道獣医師会雑誌 61 (8) 326 -326 2017年08月 [査読無し][通常論文]
  
• 組織球性大腸炎のフレンチ・ブルドッグの1例

  立花 由莉加, 大田 寛, 賀川 由美子, 佐々木 東, 森下 啓太郎, 滝口 満喜 北海道獣医師会雑誌 61 (8) 348 -348 2017年08月 [査読無し][通常論文]
  
• 後天性門脈体循環シャントを合併した先天性肝線維症の猫の1例

  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 61 (8) 345 -345 2017年08月 [査読無し][通常論文]
  
• 市販フードの給餌により栄養性二次性上皮小体機能亢進症を生じた犬の2例

  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 61 (8) 327 -327 2017年08月 [査読無し][通常論文]
  
• 犬の蛋白漏出性腸症の予後因子解析 超音波検査所見の有用性の検討

  大田 寛, 賀川 由美子, 佐々木 東, 森下 啓太郎, 滝口 満喜 北海道獣医師会雑誌 61 (8) 347 -347 2017年08月 [査読無し][通常論文]
  
• 犬の原発性免疫介在性血小板減少症(pIMT)再発症例の回顧的研究

  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 61 (8) 332 -332 2017年08月 [査読無し][通常論文]
  
• 犬慢性腸症の十二指腸粘膜におけるロイシンリッチα2糖蛋白の発現とその臨床的意義

  奥 朋哉, 大田 寛, 田村 昌大, 永田 矩之, 笹岡 一慶, Leela-arporn Rommaneeya, Dermlim Angkhana, Nisa Khoirun, 森田 智也, 大菅 辰幸, 佐々木 東, 森下 啓太郎, 滝口 満喜 日本獣医学会学術集会講演要旨集 160回 477 -477 2017年08月 [査読無し][通常論文]
  
• 全エクソームシーケンスを用いたミニチュア・ダックスフントの炎症性結直腸ポリープ感受性遺伝子の探索

  永田 矩之, 大田 寛, 横山 望, 田村 昌大, 笹岡 一慶, Leela-Arporn Rommaneeya, Dermlim Angkhana, Nisa Khoirun, 森田 智也, 大菅 辰幸, 佐々木 東, 森下 啓太郎, 滝口 満喜 日本獣医学会学術集会講演要旨集 160回 477 -477 2017年08月 [査読無し][通常論文]
  
• 犬虚血性脳血管障害における脳底動脈血流の経頭蓋超音波ドプラ法による評価

  笹岡 一慶, 大田 寛, 田村 昌大, 永田 矩之, Leela-arporn Rommaneeya, Dermlim Angkhana, Khoirun Nisa, 森田 智也, 佐々木 東, 森下 啓太郎, 滝口 満喜 日本獣医学会学術集会講演要旨集 160回 465 -465 2017年08月 [査読無し][通常論文]
  
• 慢性肺動脈塞栓性肺高血圧症モデル犬を用いたピモベンダンの作用に関する検討

  森田 智也, 中村 健介, 大菅 辰幸, 森下 啓太郎, 佐々木 東, 大田 寛, 滝口 満喜 日本獣医学会学術集会講演要旨集 160回 465 -465 2017年08月 [査読無し][通常論文]
  
• 慢性腸疾患の犬における十二指腸の定量的造影超音波法(Quantitative contrast-enhanced ultrasonography of duodenum in dogs with chronic enteropathy)

  Khoirun Nisa, 大田 寛, 横山 望, 田村 昌大, 永田 矩之, 笹岡 一慶, Dermlim Angkhana, Leela-Arporn Rommaneeya, 森田 智也, 大菅 辰幸, 佐々木 東, 森下 啓太郎, 滝口 満喜 日本獣医学会学術集会講演要旨集 160回 477 -477 2017年08月 [査読無し][通常論文]
  
• ソノポレーションを用いた膀胱内注入療法の開発 (特集 進化する超音波治療技術の最前線(1))

  佐々木 東, 工藤 信樹, 中山 翔太, 滝口 満喜 超音波techno 29 (4) 27 -30 2017年07月 [査読無し][通常論文]
  
• ポリ塩化ビフェニル(PCBs)暴露によるネコ甲状腺機能への影響評価~甲状腺ホルモンの脱ヨード化と代謝能の解析~

  水川葉月, 高居名菜, 横山望, 市居修, 滝口満喜, 野見山桂, 高口倖暉, 西川博之, 池中良徳, 池中良徳, 中山翔太, SAINNOXOI Tsend‐ayush, 田辺信介, 石塚真由美 環境化学討論会要旨集(CD-ROM) 26th ROMBUNNO.2A‐01 2017年06月05日 [査読無し][通常論文]
  
• PCBs曝露がイヌ・ネコの甲状腺ホルモン恒常性へ及ぼす影響

  高口倖暉, 野見山桂, 西川博之, 水川葉月, 田上瑠美, 芳之内結加, 横山望, 市居修, 滝口満喜, 中山翔太, 池中良徳, 石塚真由美, 岩田久人, 国末達也, 田辺信介 環境化学討論会要旨集(CD-ROM) 26th ROMBUNNO.2A‐02 2017年06月05日 [査読無し][通常論文]
  
• イエネコのin vivo長期曝露試験:デカブロモジフェニルエーテル(BDE209)は甲状腺機能亢進症を引き起こすのか?

  水川葉月, 野見山桂, 池中良徳, 池中良徳, 中山翔太, SAENGTIENCHAI Aksorn, SAINNOXOI Tsendayush, 横山望, 笹岡一慶, 市居修, KHIDKHAN Kraisiri, 高居名菜, 滝口満喜, 田辺信介, 石塚真由美 環境化学討論会要旨集(CD-ROM) 26th ROMBUNNO.2A‐03 2017年06月05日 [査読無し][通常論文]
  
• イエネコのin vivo長期曝露試験:デカブロモジフェニルエーテル(BDE209)の生体内変化

  田中啓介, 野見山桂, 水川葉月, 高口倖暉, 田上瑠美, SAENGTIENCHAI Aksorn, SAINNOXOI Tsend‐ayush, 横山望, 市居修, 滝口満喜, 中山翔太, 池中良徳, 石塚真由美, 国末達也, 田辺信介 環境化学討論会要旨集(CD-ROM) 26th ROMBUNNO.2A‐04 2017年06月05日 [査読無し][通常論文]
  
• 血清中メタボローム解析によるイエネコのPCBs毒性影響評価

  野見山桂, 西川博之, 水川葉月, 高口倖暉, SAINNOXOI Tsend‐ayush, 横山望, 市居修, 滝口満喜, 石塚真由美, 池中良徳, 中山翔太, 江口哲史, 国末達也, 田辺信介 環境化学討論会要旨集(CD-ROM) 26th ROMBUNNO.2A‐05 2017年06月05日 [査読無し][通常論文]
  
• ネコの甲状腺機能に対するポリ塩化ビフェニル(PCBs)の影響評価 甲状腺ホルモンの脱ヨード化と代謝能の解析

  水川 葉月, 高居 名菜, 横山 望, 市居 修, 滝口 満喜, 野見山 桂, 高口 倖暉, 西川 博之, 池中 良徳, 中山 翔太, Sainnoxoi Tsend-ayush, 田辺 信介, 石塚 真由美 The Journal of Toxicological Sciences 42 (Suppl.) S236 -S236 2017年06月
• 正常犬ならびに慢性僧帽弁疾患犬におけるピモベンダン投与による左心房機能の変化

  三木 伸悟, 中村 健介, 大菅 辰幸, 森田 智也, 佐々木 東, 森下 啓太郎, 大田 寛, 滝口 満喜 日本獣医麻酔外科学雑誌 48 (Suppl.1) 348 -348 2017年06月 [査読無し][通常論文]
  
• 急性圧負荷が右室にもたらす影響 心エコー図検査は何を反映しているか

  森田 智也, 中村 健介, 大菅 辰幸, 佐々木 東, 森下 啓太郎, 大田 寛, 滝口 満喜 日本獣医麻酔外科学雑誌 48 (Suppl.1) 336 -336 2017年06月 [査読無し][通常論文]
  
• 先天性門脈体循環シャントに伴う肝肺症候群および門脈肺高血圧症を疑った1例

  道下 明日香, 中村 健介, 森下 啓太郎, 佐々木 東, 大田 寛, 細谷 謙次, 賀川 由美子, 滝口 満喜 日本獣医麻酔外科学雑誌 48 (Suppl.1) 220 -220 2017年06月 [査読無し][通常論文]
  
• ネコの甲状腺機能に対するポリ塩化ビフェニル(PCBs)の影響評価~甲状腺ホルモンの脱ヨード化と代謝能の解析~

  水川葉月, 高居名菜, 横山望, 市居修, 滝口満喜, 野見山桂, 高口倖暉, 西川博之, 池中良徳, 池中良徳, 中山翔太, SAINNOXOI Tsend‐Ayush, 田辺信介, 石塚真由美 Journal of Toxicological Sciences 42 (Supplement) S236 2017年06月 [査読無し][通常論文]
   

  有機ハロゲン化合物の一種であるポリ塩化ビフェニル（PCBs）は甲状腺ホルモン（THs）の恒常性かく乱が懸念されており、実際、ヒトやげっ歯類においてはPCBs暴露により血中THs濃度の低下が認められている。ヒトの身近な動物であるネコは餌などを介してPCBsに暴露していると懸念され、THs恒常性に何らかの悪影響をもたらすことが予想される。本研究では、ネコの甲状腺機能に対するPCBsの影響を解析するため、in vivo投与試験したネコを用いて甲状腺機能への影響を解析した。血中のTHs濃度（総T4、総T3、遊離T4、遊離T3、リバースT3）を解析した結果、対照群と暴露群の間に有意な差は見られなかった。また、THsの恒常性に関与する遺伝子（甲状腺ホルモン受容体αおよびβ、脱ヨード酵素type1）の肝臓中発現量やTHs代謝に関わる酵素であるグルクロン酸抱合酵素（UGT1A1）の活性を調べたところ、対照群と暴露群の間に有意な差は見られなかった。
  本実験結果では、ネコにおいてPCBs短期暴露によるTHsへの影響が認められなかったが、日本のペットネコにおけるモニタリング調査では、血中のTHs濃度とPCBs濃度との間に負の相関が見られており、有機ハロゲン化合物によるTHsかく乱が懸念されている。また、本研究試料のメタボローム解析結果では酸化ストレスの発現、抗酸化物質、電子伝達物質の生産阻害などが示唆されており、PCBsや水酸化代謝物による内分泌撹乱作用が心配される。THsの恒常性は非常に複雑な機構のもと維持されていることが知られており、負のフィードバック機構に加え、THsの活性化や代謝、排泄の調整にも多くの遺伝子やトランスポーター、酵素など様々な要因が関わっていることから、ネコは長期的かつ慢性的に化学物質に暴露されることで、甲状腺機能などへの悪影響が現れると考えられ、内分泌撹乱作用の作用機序について解析を進めることが重要である。
• ネコの甲状腺機能に対するポリ塩化ビフェニル（PCBs）の影響評価～甲状腺ホルモンの脱ヨード化と代謝能の解析～

  水川 葉月, 中山 翔太, Tsend-ayush SAINNOXOI, 田辺 信介, 石塚 真由美, 高居 名菜, 横山 望, 市居 修, 滝口 満喜, 野見山 桂, 高口 倖暉, 西川 博之, 池中 良徳 日本毒性学会学術年会 44 (0) P -55 2017年06月 [査読無し][通常論文]
   

  有機ハロゲン化合物の一種であるポリ塩化ビフェニル（PCBs）は甲状腺ホルモン（THs）の恒常性かく乱が懸念されており、実際、ヒトやげっ歯類においてはPCBs暴露により血中THs濃度の低下が認められている。ヒトの身近な動物であるネコは餌などを介してPCBsに暴露していると懸念され、THs恒常性に何らかの悪影響をもたらすことが予想される。本研究では、ネコの甲状腺機能に対するPCBsの影響を解析するため、<i>in vivo</i>投与試験したネコを用いて甲状腺機能への影響を解析した。血中のTHs濃度（総T4、総T3、遊離T4、遊離T3、リバースT3）を解析した結果、対照群と暴露群の間に有意な差は見られなかった。また、THsの恒常性に関与する遺伝子（甲状腺ホルモン受容体αおよびβ、脱ヨード酵素type1）の肝臓中発現量やTHs代謝に関わる酵素であるグルクロン酸抱合酵素（UGT1A1）の活性を調べたところ、対照群と暴露群の間に有意な差は見られなかった。<br>本実験結果では、ネコにおいてPCBs短期暴露によるTHsへの影響が認められなかったが、日本のペットネコにおけるモニタリング調査では、血中のTHs濃度とPCBs濃度との間に負の相関が見られており、有機ハロゲン化合物によるTHsかく乱が懸念されている。また、本研究試料のメタボローム解析結果では酸化ストレスの発現、抗酸化物質、電子伝達物質の生産阻害などが示唆されており、PCBsや水酸化代謝物による内分泌撹乱作用が心配される。THsの恒常性は非常に複雑な機構のもと維持されていることが知られており、負のフィードバック機構に加え、THsの活性化や代謝、排泄の調整にも多くの遺伝子やトランスポーター、酵素など様々な要因が関わっていることから、ネコは長期的かつ慢性的に化学物質に暴露されることで、甲状腺機能などへの悪影響が現れると考えられ、内分泌撹乱作用の作用機序について解析を進めることが重要である。
• 低強度パルス超音波による毛包構成細胞への刺激

  佐々木東, 工藤信樹, 中村健介, 森下啓太郎, 大田寛, 滝口満喜 再生医療 16 348 2017年02月01日 [査読無し][通常論文]
  
• 毛包を構成する細胞に対する低強度超音波刺激

  佐々木東, 工藤信樹, 森下啓太郎, 大田寛, 滝口満喜 日本超音波医学会光超音波画像研究会プログラム・抄録集 2017 (2nd) 66‐67 2017年 [査読無し][通常論文]
  
• 犬の甲状腺機能低下症を誤診しないように 画像診断

  滝口 満喜 動物臨床医学会年次大会プロシーディング 37回 (1) 194 -194 2016年11月
• もう一度見直す超音波検査法 基本テクニックと各種疾患の診断・評価法 腹部エコー診断がどこまで治療に役立つか

  滝口 満喜 動物臨床医学会年次大会プロシーディング 37回 (1) 341 -341 2016年11月
• Post-capillary肺高血圧症ではPre-capillary肺高血圧症ほど右室機能指標は減弱しない

  森田 智也, 中村 健介, 大菅 辰幸, 佐々木 東, 森下 啓太郎, 大田 寛, 滝口 満喜 日本獣医麻酔外科学雑誌 47 (Suppl.2) 228 -228 2016年11月 [査読無し][通常論文]
  
• 3次元培養でのシスプラチンと超音波 マイクロバブルの併用

  佐々木 東, Moonen Chrit, 滝口 満喜 超音波医学 43 (5) 673 -673 2016年09月
• 超音波による細胞周期変動を利用した増感放射線療法の可能性

  藤沢 眞代, 佐々木 東, 安井 博宣, 工藤 信樹, 滝口 満喜 超音波医学 43 (5) 679 -679 2016年09月
• 膀胱癌を模した3次元培養系でのシスプラチンデリバリー

  佐々木 東, 工藤 信樹, 滝口 満喜 超音波医学 43 (5) 679 -679 2016年09月
• 3次元培養でのシスプラチンと超音波 マイクロバブルの併用

  佐々木 東, Moonen Chrit, 滝口 満喜 超音波医学 43 (5) 673 -673 2016年09月 [査読無し][通常論文]
  
• 超音波による細胞周期変動を利用した増感放射線療法の可能性

  藤沢 眞代, 佐々木 東, 安井 博宣, 工藤 信樹, 滝口 満喜 超音波医学 43 (5) 679 -679 2016年09月 [査読無し][通常論文]
  
• 膀胱癌を模した3次元培養系でのシスプラチンデリバリー

  佐々木 東, 工藤 信樹, 滝口 満喜 超音波医学 43 (5) 679 -679 2016年09月 [査読無し][通常論文]
  
• 心エコー図検査にて急性期および回復後の変化を捉えた急性肺血栓塞栓症の犬の1症例

  森田智也, 中村健介, 森下啓太郎, 竹内恭介, 大菅辰幸, 那須香菜子, 華園究, 滝口満喜 北海道獣医師会雑誌 60 (8) 417 -417 2016年08月10日 [査読無し][通常論文]
  
• 好塩基球性白血病の犬の1症例

  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 60 (8) 406 -406 2016年08月 [査読無し][通常論文]
  
• 大腸血管拡張症の犬の1症例

  竹内 恭介, 大田 寛, 高木 哲, 中島 彩乃, 佐々木 東, 森下 啓太郎, 中村 健介, 滝口 満喜 北海道獣医師会雑誌 60 (8) 418 -418 2016年08月 [査読無し][通常論文]
  
• ミニチュア・ダックスフンドの炎症性結直腸ポリープにおけるCOX-2発現とToll-like receptorとの関連性の解析

  長谷川 純也, 大田 寛, 横山 望, 笹岡 一慶, Nisa Khoirun, 森田 智也, 大菅 辰幸, 佐々木 東, 森下 啓太郎, 中村 健介, 滝口 満喜 日本獣医学会学術集会講演要旨集 159回 456 -456 2016年08月 [査読無し][通常論文]
  
• 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 2016年08月 [査読無し][通常論文]
  
• ネコにおけるポリ塩化ビフェニル(PCBs)の異物代謝機構解明と甲状腺ホルモンへの影響評価

  水川葉月, 前原美咲, 横山望, 市居修, 滝口満喜, 野見山桂, 西川博之, 池中良徳, 中山翔太, 高口倖暉, 田辺信介, 石塚真由美 環境化学討論会要旨集(CD-ROM) 25th ROMBUNNO.1A‐13 2016年06月06日 [査読無し][通常論文]
  
• メタボローム解析を用いたイエネコにおけるPCBsの毒性影響評価

  西川博之, 野見山桂, 水川葉月, 横山望, 市居修, 滝口満喜, 石塚真由美, 池中良徳, 中山翔太, 江口哲史, 国末達也, 田辺信介 環境化学討論会要旨集(CD-ROM) 25th ROMBUNNO.1A‐12 2016年06月06日 [査読無し][通常論文]
  
• 犬猫の脳疾患における造影FLAIRの使用経験

  華園究, 大田寛, 山根由久, 那須香菜子, 細谷兼次, 石塚友人, 伊丹貴晴, 滝口満喜 日本獣医麻酔外科学雑誌 47 (Supplement 1) 335 -335 2016年06月05日 [査読無し][通常論文]
  
• ポリ塩化ビフェニル(PCBs)のin vivo暴露によるネコの異物代謝解明と甲状腺ホルモンへの影響評価

  水川 葉月, 前原 美咲, 横山 望, 市居 修, 滝口 満喜, 野見山 桂, 西川 博之, 池中 良徳, 中山 翔太, 高口 倖暉, 田辺 信介, 石塚 真由美 The Journal of Toxicological Sciences 41 (Suppl.) S215 -S215 2016年06月
• Parametric Micro flow imaging法を用いて肝実質の動脈化を検出した門脈血栓症の犬の1例

  田村 昌大, 中村 健介, 森 俊輔, 森下 啓太郎, 佐々木 東, 大田 寛, 滝口 満喜 日本獣医麻酔外科学雑誌 47 (Suppl.1) 335 -335 2016年06月 [査読無し][通常論文]
  
• 間質性肺疾患による重度肺高血圧症を呈したウェルシュ・コーギーの2例

  森田 智也, 中村 健介, 大菅 辰幸, 佐々木 東, 森下 啓太郎, 大田 寛, 滝口 満喜 日本獣医麻酔外科学雑誌 47 (Suppl.1) 235 -235 2016年06月 [査読無し][通常論文]
  
• 造影超音波検査により計測した肺循環時間と慢性房室弁疾患の重症度との関係

  池田 正悟, 中村 健介, 大菅 辰幸, 森田 智也, 佐々木 東, 森下 啓太郎, 大田 寛, 滝口 満喜 日本獣医麻酔外科学雑誌 47 (Suppl.1) 323 -323 2016年06月 [査読無し][通常論文]
  
• ポリ塩化ビフェニル（PCBs）のin vivo暴露によるネコの異物代謝解明と甲状腺ホルモンへの影響評価

  水川 葉月, 前原 美咲, 横山 望, 市居 修, 滝口 満喜, 野見山 桂, 西川 博之, 池中 良徳, 中山 翔太, 高口 倖暉, 田辺 信介, 石塚 真由美 日本毒性学会学術年会 43 (0) P -6 2016年06月 [査読無し][通常論文]
   

  ポリ塩化ビフェニル（PCBs）の水酸化代謝物であるOH-PCBsは、肝臓内で薬物代謝酵素より生成され、その後体外へ排泄される。しかしながら、一部の水酸化代謝物は甲状腺ホルモン（TH）と類似の構造をもつため、THの恒常性を撹乱することが危惧されている。これまでに、多様な陸棲哺乳類の血中OH-PCBsを分析したところ、種間でOH-PCBsの組成に差異が認められ、中でも、ネコのOH-PCBs残留パターンは他種と大きく異なることから、本種は特異な代謝機能を有することが示唆された。しかし、ネコの異物代謝能の研究は僅かであり、化学物質暴露による毒性影響も不明な点が多い。本研究では、ネコにおけるPCBs <i>in vivo</i>暴露試験を実施し、体内動態および代謝に関与する酵素活性や遺伝子を解析するとともに、化学物質の暴露評価に繋がる基盤的情報の収集を目的とした。<br>コーン油に溶解した12異性体のPCBsを腹腔内投与し、経時採血した血清中PCBsおよびOH-PCBs濃度について同条件で実施したイヌの<i>in vivo</i>試験と比較した結果、異性体の残留パターンや体内動態にイヌとネコで種差が観察された。とくにネコでは低塩素化体の残留が顕著であった。また、代謝酵素活性および遺伝子解析の結果、PCBs暴露によりEROD、MROD、PROD活性は上昇するものの、第2相抱合酵素（UGTやSULT）活性は変化せず、PCBs暴露による抱合酵素活性への影響もみられなかった。また、<i>CYP1A1</i>および<i>CYP1A2</i>遺伝子の発現量の上昇も認められた。<br> 本研究により、ネコのPCBs吸収・代謝・排泄能はイヌと異なることが示唆され、とくに低塩素化OH-PCBsの毒性リスクは高いことが予想された。低塩素化OH-PCBsは血中でTH輸送タンパクとの競合結合や、THの硫酸抱合排泄の阻害、TH起因性遺伝子の転写抑制などが報告されており、ネコの甲状腺機能障害が懸念される。
• 犬の膵炎診断における客観的で簡便な指標による超音波検査の有用性の検討

  竹内 恭介, 中村 健介, 森下 啓太郎, 大田 寛, 佐々木 東, 滝口 満喜 日本獣医師会雑誌 69 (5) 292 -292 2016年05月 [査読無し][通常論文]
  
• 右心機能の低下は僧帽弁疾患犬の生存期間を短縮する

  森田 智也, 中村 健介, 大菅 辰幸, 佐々木 東, 大田 寛, 滝口 満喜 日本獣医師会雑誌 69 (5) 294 -294 2016年05月 [査読無し][通常論文]
  
• 日本の専門家が結集して作る獣医臨床腫瘍学テキストブック 消化器系(食道〜結腸・直腸、肛門) 概要

  滝口 満喜 Veterinary Oncology 3 (2) 78 -84 2016年04月
• シスプララチンデリバリーの効果が及ぶ距離

  佐々木 東, 工藤 信樹, 中村 健介, 森下 啓太郎, 大田 寛, 滝口 満喜 超音波医学 43 (Suppl.) S544 -S544 2016年04月 [査読無し][通常論文]
  
• 有機ハロゲン化合物によるコンパニオンアニマルの汚染実態と甲状腺ホルモンへの影響評価

  野見山桂, 山本恭央, 水川葉月, 江口哲史, 滝口満喜, 中山翔太, 池中良徳, 石塚真由美, 国末達也, 田辺信介 環境化学討論会要旨集(CD-ROM) 25th 2016年
• 本当にソノポレーションか?

  佐々木東, 工藤信樹, 中山翔太, 滝口満喜 日本超音波医学会光超音波画像研究会プログラム・抄録集 2016 (2nd) 22‐24 2016年 [査読無し][通常論文]
  
• 犬の急性および慢性膵炎の診断治療の最前線 膵炎の画像診断と生検診断

  滝口 満喜 動物臨床医学 24 (4) 153 -154 2015年12月
• 右心室-左心室-左心房interaction 犬急性肺高血圧症モデルにおける検討

  大菅 辰幸, 中村 健介, 森田 智也, 森下 啓太郎, 佐々木 東, 大田 寛, 滝口 満喜 日本獣医麻酔外科学雑誌 46 (Suppl.2) 251 -251 2015年12月 [査読無し][通常論文]
  
• 診察中に左房破裂による心タンポナーデを発症したものの内科療法のみで長期生存中の犬の1例

  川元 誠, 中村 健介, 高瀬 奈美, 森田 智也, 大菅 辰幸, 佐々木 東, 森下 啓太郎, 大田 寛, 滝口 満喜 日本獣医麻酔外科学雑誌 46 (Suppl.2) 241 -241 2015年12月 [査読無し][通常論文]
  
• 二次診療施設において診断・治療に苦慮した消化器疾患の症例カンファレンス 膵臓疾患編

  滝口 満喜 動物臨床医学会年次大会プロシーディング 36回 (1) 125 -125 2015年11月
• 胆管原発カルチノイドによる肝外胆管閉塞と診断した猫の1例

  森 俊輔, 中村 健介, 高木 哲, 賀川 由美子, 森下 啓太郎, 大田 寛, 滝口 満喜 動物臨床医学会年次大会プロシーディング 36回 (2) 283 -284 2015年11月 [査読無し][通常論文]
  
• 犬の非再生性免疫介在性貧血(NRIMA)に対する治療の前向き検討

  森下 啓太郎, 竹内 恭介, 森 俊輔, 早川 小百合, 中村 健介, 佐々木 東, 大田 寛, 滝口 満喜 動物臨床医学会年次大会プロシーディング 36回 (2) 367 -368 2015年11月 [査読無し][通常論文]
  
• 犬のびまん性肝疾患に対する造影超音波検査の応用の試み

  道下 明日香, 森下 啓太郎, 華園 究, 中村 健介, 滝口 満喜, 高木 哲 日本獣医画像診断学会抄録 58回 12 -12 2015年09月
• ミニチュア・ダックスフンドの炎症性結直腸ポリープ症例の結直腸粘膜におけるToll‐like receptor2,4の局在解析

  横山望, 大田寛, 賀川由美子, 山崎淳平, 市居修, KHOIRUN Nisa, 森田智也, 大菅辰幸, 佐々木東, 森下啓太郎, 中村健介, 滝口満喜 日本獣医学会学術集会講演要旨集 158th 402 -402 2015年08月30日 [査読無し][通常論文]
  
• 胸腺腫に続発した後天性重症筋無力症の猫の1例

  早川小百合, 大田寛, 細谷謙次, 賀川由美子, 華園究, 田淵祐司, 滝口満喜 北海道獣医師会雑誌 59 (8) 403 -403 2015年08月10日 [査読無し][通常論文]
  
• 【一目でわかる症候シリーズvol.4 嘔吐(1)】胃の腫瘍

  滝口 満喜 SA Medicine 17 (4) 18 -21 2015年08月
• (パート1)参加型臨床実習をどうするか 目前にせまった参加型臨床実習の内容、実施方法を議論する 伴侶動物の参加型臨床実習 国立大学編国立大学の参加型臨床実習の実施方針、実際の実施計画(伴侶動物)「国際認証を目指す伴侶動物の参加型臨床実習」

  滝口 満喜 日本獣医学会学術集会講演要旨集 158回 139 -139 2015年08月
• 汎用性が高く臨床的にも有用な犬の左心房機能評価法の検討 僧帽弁逆流の重症度評価について

  川元 誠, 中村 健介, 大菅 辰幸, 森田 智也, 佐々木 東, 森下 啓太郎, 大田 寛, 滝口 満喜 北海道獣医師会雑誌 59 (8) 390 -390 2015年08月 [査読無し][通常論文]
  
• 右心機能の低下は僧帽弁疾患犬の生存期間を短縮する

  森田 智也, 中村 健介, 大菅 辰幸, 森下 啓太郎, 佐々木 東, 大田 寛, 滝口 満喜 北海道獣医師会雑誌 59 (8) 389 -389 2015年08月 [査読無し][通常論文]
  
• 超低脂肪食で治療した犬慢性腸症18例の回顧的検討

  横山 望, 大田 寛, 佐々木 東, 森下 啓太郎, 中村 健介, 滝口 満喜 北海道獣医師会雑誌 59 (8) 394 -394 2015年08月 [査読無し][通常論文]
  
• 犬の膵炎診断における客観的で簡便な指標による超音波検査の有用性の検討

  竹内 恭介, 中村 健介, 森下 啓太郎, 佐々木 東, 大田 寛, 滝口 満喜 北海道獣医師会雑誌 59 (8) 396 -396 2015年08月 [査読無し][通常論文]
  
• 心エコー図検査による右心機能指標と心臓カテーテル検査との関連:急性肺高血圧モデル犬を用いた検討

  森田 智也, 中村 健介, 大菅 辰幸, 森下 啓太郎, 佐々木 東, 大田 寛, 滝口 満喜 日本獣医学会学術集会講演要旨集 158回 403 -403 2015年08月 [査読無し][通常論文]
  
• 免疫抑制治療中に合併したRgizopus microsporus感染に伴う胃穿孔の犬の1例

  那須 香菜子, 中村 健介, 高木 哲, 賀川 由美子, 青島 圭佑, 甲斐 千暁, 後藤 正光, 滝口 満喜 北海道獣医師会雑誌 59 (8) 392 -392 2015年08月 [査読無し][通常論文]
  
• 【副腎腫瘍】副腎腫瘍の内科

  滝口 満喜 Joncol: Japanese Journal of Veterinary Clinical Oncology 11 (2) 22 -24 2015年07月
• 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 (Supplement 1) 302 -302 2015年06月10日 [査読無し][通常論文]
  
• 右室Tei-indexは僧帽弁疾患犬の1年生存を規定する

  森田 智也, 中村 健介, 大菅 辰幸, 佐々木 東, 森下 啓太郎, 大田 寛, 滝口 満喜 日本獣医麻酔外科学雑誌 46 (Suppl.1) 280 -280 2015年06月 [査読無し][通常論文]
  
• 僧帽弁疾患犬におけるうっ血性心不全の発症はLA strain法によるブースターポンプ機能指標と関連する

  川元 誠, 中村 健介, 大菅 辰幸, 森田 智也, 佐々木 東, 森下 啓太郎, 大田 寛, 滝口 満喜 日本獣医麻酔外科学雑誌 46 (Suppl.1) 281 -281 2015年06月 [査読無し][通常論文]
  
• 肝静脈造影超音波検査による肝疾患罹患犬の肝内血行動態の評価

  森下 啓太郎, 平本 彰, 大菅 辰幸, 中村 健介, 大田 寛, 滝口 満喜 日本獣医師会雑誌 68 (5) 326 -327 2015年05月 [査読無し][通常論文]
  
• ドラッグデリバリーを可視化する培養系の開発

  佐々木 東, 滝口 満喜, Bos Clemens, Moonen Chrit 超音波医学 42 (Suppl.) S476 -S476 2015年04月
• ドラッグデリバリーを可視化する培養系の開発

  佐々木 東, 滝口 満喜, Bos Clemens, Moonen Chrit 超音波医学 42 (Suppl.) S476 -S476 2015年04月 [査読無し][通常論文]
  
• 肝静脈造影超音波検査による肝疾患罹患犬の肝内血行動態の評価

  森下啓太郎, 平本彰, 大菅辰幸, 中村健介, 大田寛, 滝口満喜 日本獣医師会獣医学術学会年次大会講演要旨集 2014 137 2015年01月30日 [査読無し][通常論文]
  
• ペットネコにおける有機ハロゲン化合物および水酸化代謝物の汚染実態と甲状腺ホルモン恒常性への影響

  山本恭央, 野見山桂, 水川葉月, 滝口満喜, 石塚真由美, 国末達也, 田辺信介 環境化学討論会要旨集(CD-ROM) 24th 2015年
• ペット動物における有機ハロゲン化合物および水酸化代謝物の曝露実態と甲状腺ホルモン恒常性へ及ぼす影響

  山本恭央, 野見山桂, 水川葉月, 滝口満喜, 石塚真由美, 国末達也, 田辺信介 日本内分泌かく乱化学物質学会研究発表会要旨集 18th 124 -124 2015年
• 犬におけるSpeckle tracking法を用いた右室strain解析の再現性

  森田 智也, 中村 健介, 大菅 辰幸, 森下 啓太郎, 大田 寛, 滝口 満喜 獣医麻酔外科学雑誌 45 (Suppl.2) 216 -216 2014年12月 [査読無し][通常論文]
  
• 犬の急性および慢性膵炎の診断治療の最前線―膵炎の画像診断と生検診断―

  滝口満喜 動物臨床医学会年次大会プロシーディング 35th (1) 209 -210 2014年11月14日 [査読無し][通常論文]
  
• うっ血性左心不全を呈した原発性心臓血管肉腫の犬の1例

  大菅 辰幸, 中村 健介, 遠山 伸夫, 森田 智也, 賀川 由美子, 森下 啓太郎, 大田 寛, 滝口 満喜 動物臨床医学会年次大会プロシーディング 35回 (2) 33 -34 2014年11月 [査読無し][通常論文]
  
• 免疫抑制量のプレドニゾロンが奏功した重度肺高血圧症を伴う間質性肺疾患を疑ったウェルシュコーギーの1例

  森田 智也, 中村 健介, 大菅 辰幸, 森下 啓太郎, 大田 寛, 滝口 満喜 動物臨床医学会年次大会プロシーディング 35回 (2) 103 -104 2014年11月 [査読無し][通常論文]
  
• NSAIDsが原因と考えられた骨髄壊死の犬の1例

  森下 啓太郎, 出口 辰也, 賀川 由美子, 中村 健介, 大田 寛, 滝口 満喜 動物臨床医学会年次大会プロシーディング 35回 (2) 93 -94 2014年11月 [査読無し][通常論文]
  
• 犬慢性消化器疾患における十二指腸造影超音波検査の有用性の検討

  篠原 正義, リン・スーイー, 森下 啓太郎, 横山 望, 大菅 辰幸, 中村 健介, 賀川 由美子, 大田 寛, 滝口 満喜 日本獣医画像診断学会抄録 56回 24 -24 2014年09月 [査読無し][通常論文]
  
• 参加型臨床実習 小動物

  滝口満喜 日本獣医学会学術集会講演要旨集 157th 192 -192 2014年08月11日 [査読無し][通常論文]
  
• 参加型臨床実習 小動物

  滝口満喜 北海道獣医師会雑誌 58 (8) 398 -398 2014年08月10日 [査読無し][通常論文]
  
• プロカルバジンが奏功した肉芽腫性髄膜脳脊髄炎を疑う犬の1例

  山口 朋生, 大田 寛, 松本 正憲, 森下 啓太郎, 中村 健介, 滝口 満喜 北海道獣医師会雑誌 58 (8) 365 -365 2014年08月 [査読無し][通常論文]
  
• 肺高血圧症の犬に対するDual pulsed-wave Doppler法を用いた右室Tei-index測定の有用性

  森田 智也, 中村 健介, 大菅 辰幸, 森下 啓太郎, 大田 寛, 滝口 満喜 北海道獣医師会雑誌 58 (8) 369 -369 2014年08月 [査読無し][通常論文]
  
• 尿管結石による水腎症から膿腎症に至った犬の1例

  早川 小百合, 中村 健介, 高木 哲, 森下 啓太郎, 大田 寛, 滝口 満喜 北海道獣医師会雑誌 58 (8) 376 -376 2014年08月 [査読無し][通常論文]
  
• 二次的な巨大食道を伴った鼻咽頭ポリープの猫の1例

  那須 香菜子, 中村 健介, 高木 哲, 森下 啓太郎, 大田 寛, 滝口 満喜 北海道獣医師会雑誌 58 (8) 374 -374 2014年08月 [査読無し][通常論文]
  
• 活性型ビタミンD3外用薬の慢性摂取により高カルシウム血症が認められた犬の2例

  下出 亜里咲, 中村 健介, 森下 啓太郎, 大田 寛, 滝口 満喜 北海道獣医師会雑誌 58 (8) 379 -379 2014年08月 [査読無し][通常論文]
  
• 肝静脈造影超音波検査による肝疾患罹患犬の肝内血行動態の評価

  森下 啓太郎, 平本 彰, リン・スー・イー, 大菅 辰幸, 中村 健介, 大田 寛, 滝口 満喜 北海道獣医師会雑誌 58 (8) 370 -370 2014年08月 [査読無し][通常論文]
  
• 左心房機能は心血管薬によりいかに変化するか 正常犬における2D Speckle Tracking法を用いた検討

  大菅 辰幸, 中村 健介, 森田 智也, Lim Sue Yee, 横山 望, 森下 啓太郎, 大田 寛, 滝口 満喜 日本獣医学会学術集会講演要旨集 157回 479 -479 2014年08月 [査読無し][通常論文]
  
• ミニチュア・ダックスフンドの炎症性結直腸ポリープ症例の結直腸粘膜におけるclaudinの蛋白質発現解析

  横山 望, 大田 寛, 森田 智也, 大菅 辰幸, Lim Sue Yee, 森下 啓太郎, 中村 健介, 滝口 満喜 日本獣医学会学術集会講演要旨集 157回 491 -491 2014年08月 [査読無し][通常論文]
  
• 犬バベシア症治療における熱ショック蛋白質90の薬剤標的としての可能性

  阿部 萌子, 山崎 真大, 大田 寛, 滝口 満喜 日本獣医学会学術集会講演要旨集 157回 361 -361 2014年08月 [査読無し][通常論文]
  
• 犬の非感染性髄膜脳炎症例の脳脊髄液中におけるサイトカインの発現解析

  大田寛, 鎌田真由美, 森下啓太郎, 中村健介, 山崎真大, 滝口満喜 獣医神経病学会 40th 19 2014年07月05日 [査読無し][通常論文]
  
• 犬胃癌10症例における超音波検査所見

  横山 望, 大田 寛, 中村 健介, 森下 啓太郎, 山崎 真大, 滝口 満喜 獣医麻酔外科学雑誌 45 (Suppl.1) 261 -261 2014年06月 [査読無し][通常論文]
  
• 造影超音波検査による腎機能評価の基礎的検討

  森下 啓太郎, リン・スー・イー, 大菅 辰幸, 中村 健介, 大田 寛, 山崎 真大, 滝口 満喜 獣医麻酔外科学雑誌 45 (Suppl.1) 262 -262 2014年06月 [査読無し][通常論文]
  
• 徐脈性不整脈に対してピモベンダンを投与し失神の改善を認めた犬の1例

  森田 智也, 鈴木 周二, 中村 健介, 大菅 辰幸, 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 45 (Suppl.1) 248 -248 2014年06月 [査読無し][通常論文]
  
• 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, 鈴木周二, 森下啓太郎, 山崎真大, 滝口満喜 日本獣医師会雑誌 67 (5) 367 -367 2014年05月20日 [査読無し][通常論文]
  
• プレドニゾロンを主とする免疫抑制療法実施症例における犬膵特異的リパーゼの推移

  大田 寛, 森下 啓太郎, 中村 健介, 山崎 真大, 滝口 満喜 日本獣医師会雑誌 67 (5) 369 -369 2014年05月 [査読無し][通常論文]
  
• セルレイン誘発膵炎犬における造影超音波検査の定量的および定性的評価

  Lim Sue Yee, 中村 健介, 森下 啓太郎, 大田 寛, 山崎 真大, 滝口 満喜 獣医畜産新報 67 (4) 286 -288 2014年04月 [査読無し][通常論文]
   

  本研究ではコレシストキニン類似体セルレインによる急性膵炎モデル犬を使用して、急性膵炎の診断における造影超音波検査の有用性を検討することを目的とした。その結果、造影超音波検査は微小血管の変化を検出することが可能であり、これにより膵臓における炎症の存在を検出できる可能性が示された。特に、セルレイン誘発膵炎においては持続した強い造影増強が認められることが特徴的な所見であることが示された。(著者抄録)
• 北海道での小動物臨床での放射線利用の広がり

  滝口満喜 日本アイソトープ協会放射線安全取扱部会年次大会要旨集 2014 57 2014年 [査読無し][通常論文]
  
• LC-MS/MS Analysis of Canine Lipoproteins Fractionated Using the Ultracentrifugation-Precipitation Method (vol 75, pg 1471, 2013)

  Asuka Suto, Masahiro Yamasaki, Yukari Takasaki, Yasuyuki Fujita, Riichiro Abe, Hiroshi Shimizu, Hiroshi Ohta, Mitsuyoshi Takiguchi JOURNAL OF VETERINARY MEDICAL SCIENCE 75 (12) 1678 -1678 2013年12月 [査読無し][通常論文]
  
• Dual pulsed-wave doppler法による右室Tei-index測定の再現性

  森田 智也, 中村 健介, 大菅 辰幸, 鈴木 周二, 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.2) 250 -250 2013年12月 [査読無し][通常論文]
  
• 猫心筋症において2D Speckle Tracking法を用いた左心房機能評価は可能であるのか

  大菅 辰幸, 中村 健介, 鈴木 周二, 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.2) 249 -249 2013年12月 [査読無し][通常論文]
  
• 両側性尿管閉塞を呈した犬の1例

  遠山 伸夫, 中村 健介, 賀川 由美子, 森下 啓太郎, 大田 寛, 高木 哲, 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) 3 -4 2013年11月 [査読無し][通常論文]
  
• 非典型的溶血性尿毒症症候群(D-HUS)が疑われた犬の1例

  森下 啓太郎, 遠山 伸夫, 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) 141 -142 2013年11月 [査読無し][通常論文]
  
• 慢性特発性偽性腸閉塞症が疑われた犬の1例

  横山 望, 大田 寛, 橋場 香野, 森下 啓太郎, 中村 健介, 山崎 真大, 落合 謙爾, 寺本 英司, 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) 59 -60 2013年11月 [査読無し][通常論文]
  
• 市販フードの給餌によって病的骨折を起こした栄養性二次性上皮小体機能亢進症の犬の1例

  橋場 香野, 森下 啓太郎, 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) 119 -120 2013年11月 [査読無し][通常論文]
  
• 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 2013年11月 [査読無し][通常論文]
  
• 超音波検査により診断が可能であった子宮捻転の犬の1例

  中村 健介, 山崎 真大, 大田 寛, 森下 啓太郎, 木村 享史, 滝口 満喜 日本獣医画像診断学会抄録 54回 28 -28 2013年09月 [査読無し][通常論文]
  
• 胆嚢十二指腸吻合および胆嚢肝管吻合を行った胆管閉塞の猫の1症例

  姉川啓文, 高木哲, 橋場香野, 細谷謙次, 星野有希, 滝口満喜, 奥村正裕 北海道獣医師会雑誌 57 (8) 400 -400 2013年08月10日 [査読無し][通常論文]
  
• プレドニゾロンを主とする免疫抑制療法実施症例における犬膵特異的リパーゼの推移

  大田 寛, 森下 啓太郎, 中村 健介, 山崎 真大, 滝口 満喜 北海道獣医師会雑誌 57 (8) 402 -402 2013年08月 [査読無し][通常論文]
  
• 輪状咽頭アカラシアの犬の1例

  植野 孝志, 大田 寛, 高木 哲, 星 清貴, 森下 啓太郎, 中村 健, 山崎 真大, 滝口 満喜 北海道獣医師会雑誌 57 (8) 401 -401 2013年08月 [査読無し][通常論文]
  
• 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 2013年08月 [査読無し][通常論文]
  
• 非典型的溶血性尿毒症症候群(D-HUS)が疑われた犬の1例

  遠山 伸夫, 森下 啓太郎, 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) 395 -395 2013年08月 [査読無し][通常論文]
  
• 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 2013年08月 [査読無し][通常論文]
  
• ジミナゼン耐性Babesia gibsoniの熱ショック蛋白質90遺伝子発現量の測定

  井高 菜月, 山崎 真大, 大田 寛, 滝口 満喜 日本獣医学会学術集会講演要旨集 156回 236 -236 2013年08月 [査読無し][通常論文]
  
• 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 2013年06月 [査読無し][通常論文]
  
• QUALITATIVE AND QUANTITATIVE CONTRAST ENHANCED ULTRASONOGRAPHIC ASSESSMENT OF CERULEIN-INDUCED PANCREATITIS IN DOGS

  S. Y. Lim, K. Nakamura, K. Morishita, H. Ohta, M. Yamasaki, M. Takiguchi JOURNAL OF VETERINARY INTERNAL MEDICINE 27 (3) 707 -707 2013年05月 [査読無し][通常論文]
  
• MARKED INCREASED EXPRESSION OF INTERLEUKIN 8 IN THE COLORECTAL MUCOSA OF DOGS WITH INFLAMMATORY COLORECTAL POLYPS BUT NOT WITH LYMPHOCYTIC-PLASMACYTIC COLITIS

  Y. Tamura, H. Ohta, N. Yokoyama, K. Morishita, K. Nakamura, M. Yamasaki, M. Takiguchi JOURNAL OF VETERINARY INTERNAL MEDICINE 27 (3) 706 -706 2013年05月 [査読無し][通常論文]
  
• モバイル超音波時代の幕開け

  滝口満喜 MVM 22 (4) 61 -63 2013年05月01日 [査読無し][通常論文]
  
• 肝静脈血流波形解析による右心不全の重症度評価

  中村 健介, 大菅 辰幸, 森下 啓太朗, 大田 寛, 山崎 真大, 滝口 満喜 日本獣医師会雑誌 66 (5) 346 -347 2013年05月 [査読無し][通常論文]
  
• 内科領域の取り組みと課題

  辻本元, 奥田優, 滝口満喜 日本獣医学会学術集会講演要旨集 155th 150 -150 2013年03月04日 [査読無し][通常論文]
  
• 小動物の炎症性腸疾患研究の最前線 ミニチュア・ダックスフンドの炎症性結直腸ポリープの病態

  大田 寛, 田村 悠, 横山 望, 森下 啓太郎, 中村 健介, 山崎 真大, 滝口 満喜 日本獣医学会学術集会講演要旨集 155回 153 -153 2013年03月 [査読無し][通常論文]
  
• Babesia gibsoni熱ショック蛋白質90の遺伝子クローニングおよび系統樹解析

  山崎真大, 坪井嘉啓, 大田寛, 滝口満喜 日本寄生虫学会大会プログラム・抄録集 82nd 84 2013年02月 [査読無し][通常論文]
  
• “診る目を養う”超音波検査 第12回 膵臓を極める

  滝口満喜 SA Med 15 (1) 18 -22 2013年02月01日 [査読無し][通常論文]
  
• 開業獣医師のための画像診断再入門 実例から学ぶ画像診断ピットフォール

  滝口満喜 MVM 22 (1) 31 -36 2013年01月01日 [査読無し][通常論文]
  
• ―免疫抑制剤の理論と実践―炎症性腸疾患の概要と免疫抑制剤使用の考え方

  滝口満喜 CAP (Companion Anim Pract) 27 (282) 19 -23 2012年12月01日 [査読無し][通常論文]
  
• 末梢肺動脈狭窄症と診断した高齢猫の1例

  大菅 辰幸, 中村 健介, 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 43 (Suppl.2) 213 -213 2012年12月 [査読無し][通常論文]
  
• 最近よく診る消化器疾患の診断と治療―IBD,胃運動性障害等の対策について―

  滝口満喜 動物臨床医学会年次大会プロシーディング 33rd (3) 223 -225 2012年11月16日 [査読無し][通常論文]
  
• Babesia gibsoniにおけるdiminazene aceturate耐性の性質の安定性

  B.K.・ウィクラマセカラ・ラジャパクシャゲ, 山崎 真大, S.J.・ファン, 中村 健介, 佐々木 東, 村上 正紘, 田村 悠, S.Y.・リン, 大田 寛, 滝口 満喜 獣医寄生虫学会誌 11 (1) 35 -35 2012年10月 [査読無し][通常論文]
  
• “診る目を養う”超音波検査 第11回 内分泌疾患を超音波で診る(2)甲状腺・上皮小体

  滝口満喜 SA Med 14 (5) 81 -87 2012年10月01日 [査読無し][通常論文]
  
• ソナゾイド造影超音波検査と機械学習を組み合わせた脾臓腫瘤の自動良悪性鑑別の試み

  中村 健介, 滝口 満喜, 高木 一也, 近藤 敏志 日本獣医画像診断学会抄録 52回 16 -16 2012年09月
• 北海道の飼育犬におけるCapnocytophaga属菌の侵淫調査

  畠中優唯, 滝口満喜, 後藤正光, 村松康和 日本獣医学会学術集会講演要旨集 154th 270 -270 2012年08月31日 [査読無し][通常論文]
  
• 披裂軟骨背側に形成された炎症性腫瘤病変を喉頭切開により摘出した猫の1例

  岩野公美, 高木哲, 星野有希, 細谷謙次, 滝口満喜, 奥村正裕 北海道獣医師会雑誌 56 (8) 411 -411 2012年08月10日 [査読無し][通常論文]
  
• 好酸球増多症候群を伴った消化器型リンパ腫の猫の1例

  遠山 伸夫, 細谷 謙次, 中村 健介, 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 56 (8) 399 -399 2012年08月 [査読無し][通常論文]
  
• 下垂体性副腎皮質機能亢進症とクロム親和性細胞腫を併発した犬の1例

  金澤 智則, 中村 健介, 山崎 真大, 大田 寛, 高木 哲, 滝口 満喜 北海道獣医師会雑誌 56 (8) 410 -410 2012年08月 [査読無し][通常論文]
  
• 麻酔後の全脳虚血が疑われた2症例のMRI所見

  大田 寛, 森下 啓太郎, 中村 健介, 山崎 真大, 滝口 満喜 北海道獣医師会雑誌 56 (8) 429 -429 2012年08月 [査読無し][通常論文]
  
• 肝静脈血流波形解析による右心不全の重症度評価

  中村 健介, 大菅 辰幸, 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 56 (8) 409 -409 2012年08月 [査読無し][通常論文]
  
• 両側性子宮分節性無形成から片側性子宮角捻転に至った犬の1例

  横山 望, 中村 健介, 木村 享史, 大田 寛, 山崎 真大, 滝口 満喜 北海道獣医師会雑誌 56 (8) 418 -418 2012年08月 [査読無し][通常論文]
  
• 下垂体性副腎皮質機能亢進症と中枢性尿崩症を併発し、放射線治療を行った下垂体腫瘍の犬の1例

  田村 悠, 山崎 真大, 森下 啓太郎, 中村 健介, 大田 寛, 滝口 満喜 北海道獣医師会雑誌 56 (8) 410 -410 2012年08月 [査読無し][通常論文]
  
• Diminazene aceturate耐性Babesia gibsoniの核酸取り込み量の測定

  渡邊 夏央, 山崎 真大, Kumara W.R. Bandula, 大田 寛, 滝口 満喜 日本獣医学会学術集会講演要旨集 154回 215 -215 2012年08月 [査読無し][通常論文]
  
• ミニチュア・ダックスフンドの炎症性結直腸ポリープ病変における炎症性サイトカインの発現解析

  田村 悠, 大田 寛, 村上 正紘, Bandula Kumara W.R., Sue Yee Lim, 大菅 辰幸, 森下 啓太郎, 中村 健介, 山崎 真大, 滝口 満喜 日本獣医学会学術集会講演要旨集 154回 307 -307 2012年08月 [査読無し][通常論文]
  
• 腎細胞癌移植マウスにおけるマルチキナーゼ阻害剤Sorafenib治療後のFLTによる治療反応評価

  村上 正紘, 趙 松吉, 趙 芫, チョウドリ・ヌスラット・ファティマ, 于 聞文, 西嶋 剣一, 久保 直樹, 滝口 満喜, 玉木 長良, 久下 裕司 核医学 49 (3) S246 -S246 2012年08月 [査読無し][通常論文]
  
• 犬の頭蓋内疾患診断における経頭蓋超音波ドプラ法の有用性の検討

  笹岡 一慶, 中村 健介, 森下 啓太郎, 大菅 辰幸, Lim Sue Yee, 大田 寛, 山崎 真大, 滝口 満喜 獣医麻酔外科学雑誌 43 (Suppl.1) 270 -270 2012年06月 [査読無し][通常論文]
  
• CT検査を実施した肝葉捻転の犬の2例

  森下 啓太郎, 細谷 謙次, 高木 哲, 中村 健介, 大田 寛, 山崎 真大, 滝口 満喜 獣医麻酔外科学雑誌 43 (Suppl.1) 267 -267 2012年06月 [査読無し][通常論文]
  
• 房室ブロックの犬2例に認められた低速僧帽弁逆流と高速左室駆出血流

  中村 健介, 遠山 伸夫, 植野 孝志, 森下 啓太郎, 大菅 辰幸, 大田 寛, 山崎 真大, 滝口 満喜 獣医麻酔外科学雑誌 43 (Suppl.1) 245 -245 2012年06月 [査読無し][通常論文]
  
• “診る目を養う”超音波検査 第10回 内分泌疾患を超音波で診る(1)副腎を極める

  滝口満喜 SA Med 14 (3) 68 -73 2012年06月01日 [査読無し][通常論文]
  
• LEFT ATRIAL FUNCTION ANALYSIS BY LEFT ATRIAL TRACKING METHOD IN CANINE CHRONIC MITRAL VALVULAR HEART DISEASE.

  K. Nakamura, T. Osuga, M. Yamasaki, H. Ohta, M. Takiguchi JOURNAL OF VETERINARY INTERNAL MEDICINE 26 (3) 720 -720 2012年05月 [査読無し][通常論文]
  
• INTERLEUKIN-17A GENE EXPRESSION IN THE INTESTINAL MUCOSA IN DOGS WITH LYMPHOCYTIC-PLASMACYTIC ENTERITIS AND INFLAMMATORY COLORECTAL POLYP

  H. Ohta, K. Takada, Y. Tamura, K. Nakamura, M. Yamasaki, M. Takiguchi JOURNAL OF VETERINARY INTERNAL MEDICINE 26 (3) 772 -773 2012年05月 [査読無し][通常論文]
  
• 18F-FMISOを用いた腎細胞癌移植モデルにおける抗血管新生療法(sorafenib)の早期治療反応の評価

  村上 正紘, 趙 松吉, 趙 芫, チョウドリ・ヌスラットファティマ, 于 聞文, 西嶋 剣一, 滝口 満喜, 玉木 長良, 久下 裕司 JSMI Report 5 (2) 117 -117 2012年05月 [査読無し][通常論文]
  
• パルス超音波を用いたソノポレーションの実現に向けたいくつかの基礎的検討

  工藤信樹, 佐々木東, 滝口満喜 超音波医学 39 (Suppl.) S174 -S174 2012年04月15日 [査読無し][通常論文]
  
• 診断装置によるソノポレーションの特徴と条件設定

  佐々木東, 中村健介, 工藤信樹, 滝口満喜 超音波医学 39 (2) 226 -227 2012年03月15日 [査読無し][通常論文]
  
• ジミナゼン耐性株および野生株におけるBabesia gibsoniミトコンドリアDNAの塩基配列の比較

  ウイクラマセカラ B.K., ラジャパク・シャゲ, 山崎 真大, 中村 健介, 佐々木 東, 村上 正紘, 田村 悠, リン S.Y., 大田 寛, 滝口 満喜 獣医寄生虫学会誌 10 (1-2) 34 -34 2012年03月 [査読無し][通常論文]
  
• Babesia gibsoniにおけるdiminazene aceturate抵抗性の安定性(Stability of characteristic of the diminazene aceturate resistance in Babesia gibsoni)

  Rajapakshage Bandula Kumara Wickramasekara, 山崎 真大, Hwang Shiang-Jyi, 中村 健介, 佐々木 東, 村上 正紘, 田村 悠, Lim Sue Yee, 大田 寛, 滝口 満喜 日本獣医学会学術集会講演要旨集 153回 221 -221 2012年03月 [査読無し][通常論文]
  
• 臨床の立場から臨床薬理学に期待するもの

  滝口満喜 日本獣医学会学術集会講演要旨集 153rd 147 -147 2012年03月01日 [査読無し][通常論文]
  
• 診断シリーズ vol.1 肝胆道系疾患 X線検査

  滝口満喜 SA Med 14 (1) 37 -39 2012年02月01日 [査読無し][通常論文]
  
• 診断シリーズ vol.1 肝胆道系疾患 超音波検査

  滝口満喜 SA Med 14 (1) 40 -44 2012年02月01日 [査読無し][通常論文]
  
• ここまでは押さえておこう! 腹部エコー検査

  滝口 満喜 日本獣医画像診断学会抄録 50回 59 -59 2012年01月
• 麻酔後の全脳虚血が疑われた猫2例のMRI所見

  大田 寛, 山崎 真大, 滝口 満喜 日本獣医画像診断学会抄録 50回 94 -94 2012年01月 [査読無し][通常論文]
  
• “診る目を養う”超音波検査 第9回 嘔吐の原因を超音波で探る(4)腸管を極める その2

  滝口満喜 SA Med 13 (6) 55 -58 2011年12月01日 [査読無し][通常論文]
  
• 心エコー図検査にて心内膜心筋線維症と診断した猫4例

  中村 健介, 山崎 真大, 大田 寛, 村上 正紘, 松山 新, 滝口 満喜 獣医麻酔外科学雑誌 42 (Suppl.2) 233 -233 2011年12月 [査読無し][通常論文]
  
• 活性型ビタミンD₃外用薬(マキサカルシトール軟膏)常用患者の飼育犬に認められた高カルシウム血症

  遠山伸夫, 中村健介, 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 32nd (2) 149 -150 2011年11月18日 [査読無し][通常論文]
  
• 最近よく診る消化器疾患の傾向と対策―確実な診断と治療を行うには―

  滝口満喜 動物臨床医学会年次大会プロシーディング 32nd (3) 185 -185 2011年11月18日 [査読無し][通常論文]
  
• 内分泌疾患の画像診断

  滝口満喜 動物臨床医学会年次大会プロシーディング 32nd (1) 100 -100 2011年11月18日 [査読無し][通常論文]
  
• 小型犬における下垂体性副腎皮質機能亢進症の超音波診断基準

  松山新, 遠山伸夫, 村上正紘, 中村健介, 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 32nd (3) 14 -18 2011年11月18日 [査読無し][通常論文]
  
• ポリエン系抗生物質アムホテリシンBのイヌバベシア症治療薬としての応用に関する研究

  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 32nd (3) 91 -94 2011年11月18日 [査読無し][通常論文]
  
• 超音波診断装置および超音波造影剤による抗がん剤の抗腫瘍効果の増強

  佐々木東, 中村健介, 工藤信樹, 滝口満喜 超音波医学 38 (6) 674 -674 2011年11月15日 [査読無し][通常論文]
  
• 最近よく診る消化器疾患の診断と治療

  滝口満喜 MVM 20 (7) 82 -87 2011年11月01日 [査読無し][通常論文]
  
• 犬の肝臓腫瘤診断におけるソナゾイド造影超音波検査 4年間の検討

  中村 健介, 山崎 真大, 大田 寛, 細谷 謙次, 高木 哲, 滝口 満喜 動物臨床医学会年次大会プロシーディング 32回 (3) 6 -9 2011年11月 [査読無し][通常論文]
  
• “診る目を養う”超音波検査 第8回 嘔吐の原因を超音波で探る(3)腸管を極める その1

  滝口満喜 SA Med 13 (5) 79 -83 2011年10月01日 [査読無し][通常論文]
  
• セフォベシンが有効であった巨大食道症に併発した誤嚥性肺炎の犬の一例

  滝口満喜 CAP (Companion Anim Pract) 26 (268) 78 -80 2011年10月01日 [査読無し][通常論文]
  
• 犬の嘔吐の治療および管理の実際と対応 制吐剤の効果的な使い方

  滝口 満喜, 大野 耕一, 竹内 和義, 峯岸 則之, 米元 仁 CLINIC NOTE 7 (9) 77 -83 2011年09月
• 病理組織検査にて角層下および真皮への多数の好酸球の浸潤が認められた犬の2症例

  千葉 依里, 山崎 真大, 大田 寛, 中村 健介, 佐々木 東, 村上 正絋, 田村 悠, Lim Sue Yee, Kumara Wickramasekara Rajapakshage Bandula, 本田 英隆, 那須野 豊彦, 落合 謙爾, 滝口 満喜 獣医臨床皮膚科 17 (3) 177 -182 2011年09月 [査読無し][通常論文]
  
• ジミナゼンアセチュレート耐性Babesia gibsoni株と野生型におけるミトコンドリアDNA配列の比較(Comparison of the sequence of mitochondrial DNA from diminazene aceturate resistance Babesia gibsoni strain with those from wild type)

  Rajapakshage Bandula Kumara Wickramasekara, 山崎 真大, 中村 健介, 佐々木 東, 村上 正紘, 田村 悠, Lim Sue Yee, 大田 寛, 滝口 満喜 日本獣医学会学術集会講演要旨集 152回 203 -203 2011年08月 [査読無し][通常論文]
  
• セフォベシンが有効であった好中球性胆管炎の猫の一例

  滝口満喜 CAP (Companion Anim Pract) 26 (266) 84 -86 2011年08月01日 [査読無し][通常論文]
  
• ”診る目を養う”超音波検査 第7回 嘔吐の原因を超音波で探る(2)胃の超音波検査 その2

  滝口満喜 SA Med 13 (4) 70 -73 2011年08月01日 [査読無し][通常論文]
  
• 犬の僧帽弁閉鎖不全症におけるLeft atrial tracking法を用いた左心房機能評価の有用性

  大菅 辰幸, 中村 健介, 大田 寛, 山崎 真大, 滝口 満喜 北海道獣医師会雑誌 55 (8) 386 -386 2011年08月 [査読無し][通常論文]
  
• 後鼻孔領域に炎症性ポリープを認めた若齢犬の1例

  渡邉 武史, 大田 寛, 曽野 文雄, 山崎 真大, 滝口 満喜 北海道獣医師会雑誌 55 (8) 387 -387 2011年08月 [査読無し][通常論文]
  
• 気腫性胆嚢炎の犬の1例

  田村 悠, 山崎 真大, 中村 健介, 大田 寛, 滝口 満喜 北海道獣医師会雑誌 55 (8) 386 -386 2011年08月 [査読無し][通常論文]
  
• 胃癌の犬5例における超音波検査および内視鏡検査所見の特徴

  遠山 伸夫, 大田 寛, 高木 哲, 山崎 真大, 滝口 満喜 北海道獣医師会雑誌 55 (8) 397 -397 2011年08月 [査読無し][通常論文]
  
• 心エコー図検査とD-dimer測定により診断し得た肺血栓塞栓症の犬の1例

  小儀 直子, 中村 健介, 山崎 真大, 大田 寛, 滝口 満喜 北海道獣医師会雑誌 55 (8) 385 -385 2011年08月 [査読無し][通常論文]
  
• 超音波診断装置および超音波造影剤による抗がん剤のソノポレーションの抗腫瘍効果

  佐々木 東, 中村 健介, 村上 正紘, Kumara Bandula W.R., Lim Sue Yee, 田村 悠, 大田 寛, 山崎 真大, 滝口 満喜 日本獣医学会学術集会講演要旨集 152回 302 -302 2011年08月 [査読無し][通常論文]
  
• 犬の慢性腸炎症例の腸粘膜におけるIL-17A遺伝子の発現解析

  高田 佳苗, 大田 寛, 中村 健介, 佐々木 東, 村上 正紘, Kumara Bandula W.R., 田村 悠, Lim Sue Yee, 山崎 真大, 滝口 満喜 日本獣医学会学術集会講演要旨集 152回 298 -298 2011年08月 [査読無し][通常論文]
  
• プロテオーム解析を用いた犬リポ蛋白質測定法の評価

  須藤 明日香, 山崎 真大, 中村 健介, 佐々木 東, 村上 正紘, Kumara Bandula W.R., 田村 悠, Lim Sue Yee, 大田 寛, 滝口 満喜 日本獣医学会学術集会講演要旨集 152回 291 -291 2011年08月 [査読無し][通常論文]
  
• 犬の慢性腸炎症例の結腸粘膜における細胞接着分子クローディンの発現変動

  大田 寛, 田村 悠, Lim Sue Yee, Kumara Bandula W.R., 村上 正紘, 佐々木 東, 中村 健介, 山崎 真大, 滝口 満喜 日本獣医学会学術集会講演要旨集 152回 298 -298 2011年08月 [査読無し][通常論文]
  
• 門脈体循環シャント(前編)門脈体循環シャントの画像診断:超音波検査

  滝口満喜, 中村健介 Surgeon 15 (4) 33 -38 2011年07月01日 [査読無し][通常論文]
  
• ”診る目を養う”超音波検査 第6回 嘔吐の原因を超音波で探る(1)胃の超音波検査

  滝口満喜, 中村健介 SA Med 13 (3) 72 -78 2011年06月01日 [査読無し][通常論文]
  
• 治療シリーズ Vol.10―私はこうしている―「肝胆道系・膵外分泌疾患」胆嚢炎

  滝口満喜 SA Med 13 (3) 50 -51 2011年06月01日 [査読無し][通常論文]
  
• 犬の心疾患におけるLeft atrial tracking法を用いた左心房機能評価の有用性

  大菅 辰幸, 中村 健介, 大田 寛, 山崎 真大, 滝口 満喜 獣医麻酔外科学雑誌 42 (Suppl.1) 243 -243 2011年06月 [査読無し][通常論文]
  
• 治療シリーズ Vol.10―私はこうしている―「肝胆道系・膵外分泌疾患」胆石症

  滝口満喜 SA Med 13 (3) 51 -52 2011年06月01日 [査読無し][通常論文]
  
• 仮想気管支鏡検査が診断に有用であった肺葉捻転の犬の2例

  村上 正紘, 中村 健介, 佐々木 東, 松山 新, 田村 悠, 大田 寛, 山崎 真大, 滝口 満喜 獣医麻酔外科学雑誌 42 (Suppl.1) 264 -264 2011年06月 [査読無し][通常論文]
  
• 犬の肝カルチノイド4症例におけるソナゾイド造影超音波検査所見

  中村 健介, 細谷 謙次, 山崎 真大, 大田 寛, Lim Sue Yee, 滝口 満喜 獣医麻酔外科学雑誌 42 (Suppl.1) 261 -261 2011年06月 [査読無し][通常論文]
  
• EFFECTS OF SILDENAFIL CITRATE ON DOGS WITH EISENMENGER'S SYNDROME

  K. Nakamura, M. Yamasaki, H. Ohta, M. Takiguchi JOURNAL OF VETERINARY INTERNAL MEDICINE 25 (3) 660 -660 2011年05月 [査読無し][通常論文]
  
• パルス超音波と微小気泡によるシスプラチンの抗腫瘍効果増強の基礎的知見

  佐々木 東, 中村 健介, 村上 正紘, 大田 寛, 山崎 真大, 工藤 信樹, 滝口 満喜 超音波医学 38 (3) 338 -338 2011年05月 [査読無し][通常論文]
  
• “診る目を養う”超音波検査 第5回 門脈シャントを超音波で診断する

  中村健介, 滝口満喜 SA Med 13 (2) 86 -90 2011年04月01日 [査読無し][通常論文]
  
• 診断用超音波とマイクロバブルによるドラッグデリバリーのin vitroでの最適化

  佐々木 東, 中村 健介, 村上 正紘, Kumara Badula, 大田 寛, 山崎 真大, 工藤 信樹, 滝口 満喜 超音波医学 38 (Suppl.) S316 -S316 2011年04月 [査読無し][通常論文]
  
• シトシンアラビノシドにより良好に維持されている特発性脳炎の犬の2例

  大田寛, 佐々木東, 村上正紘, 中村健介, 山崎真大, 滝口満喜 日本獣医皮膚科学会学術大会・総会 14th (Vol.1) 117 2011年03月11日 [査読無し][通常論文]
  
• 二次性赤血球増加症を伴ったEisenmenger症候群の犬に対するシルデナフィルの有効性の検討

  中村健介, 山崎真大, 大田寛, 滝口満喜 日本獣医皮膚科学会学術大会・総会 14th (Vol.1) 175 2011年03月11日 [査読無し][通常論文]
  
• 内分泌疾患の画像診断

  滝口満喜 日本獣医皮膚科学会学術大会・総会 14th (Vol.2) 272 2011年03月11日 [査読無し][通常論文]
  
• 超音波とマイクロバブルによるドラッグデリバリーに薬剤濃度とバブル濃度が及ぼす影響

  佐々木東, 中村健介, 村上正紘, KUMARA Bandula, 田村悠, YEE Lim Sue, 大田寛, 山崎真大, 滝口満喜 日本獣医皮膚科学会学術大会・総会 14th (Vol.1) 183 2011年03月11日 [査読無し][通常論文]
  
• アムホテリシンBによるイヌバベシア症の治療に関する研究

  山崎 真大, 黄 香寂, Bandula Kumara W.R., 谷山 祐介, 坪井 嘉啓, 大田 寛, 滝口 満喜 日本獣医学会学術集会講演要旨集 151回 216 -216 2011年03月 [査読無し][通常論文]
  
• 甲状腺の外科(外科適応となる)甲状腺疾患の病態と診断

  滝口満喜 Surgeon 15 (2) 8 -17 2011年03月01日 [査読無し][通常論文]
  
• 第二世代超音波造影剤ソナゾイドを用いた造影超音波検査による犬の肝臓および脾臓腫瘤の診断に関する研究

  中村 健介, 高木 哲, 山崎 真大, 大田 寛, 佐々木 東, 村上 正紘, 田村 悠, 滝口 満喜 日本獣医学会学術集会講演要旨集 151回 82 -82 2011年03月 [査読無し][通常論文]
  
• アムホテリシンBのin vivoにおける抗バベシア効果に関する研究

  山崎真大, HWANG Shiang‐Jyi, KUMARA W.R.Bandula, 谷山祐介, 坪井嘉啓, 大田寛, 滝口満喜 日本寄生虫学会大会プログラム・抄録集 80th 73 2011年02月 [査読無し][通常論文]
  
• “診る目を養う”超音波検査 第4回 肝臓腫瘤を超音波で鑑別する

  中村健介, 滝口満喜 SA Med 13 (1) 101 -107 2011年02月01日 [査読無し][通常論文]
  
• シトシンアラビノシドが奏効した肉芽腫性髄膜脳脊髄炎疑いの犬の1例

  大田 寛, 山崎 真大, 滝口 満喜 北海道獣医師会雑誌 55 (1) 9 -11 2011年01月 [査読無し][通常論文]
  
• “診る目を養う”超音波検査 第3回 黄疸を超音波で鑑別する(2)肝実質の超音波検査

  中村健介, 滝口満喜 SA Med 12 (6) 65 -69 2010年12月01日 [査読無し][通常論文]
  
• 急性膵炎とどう戦う―急性膵炎の病態生理と診断―

  滝口満喜 動物臨床医学会年次大会プロシーディング 31st (3) 152 -153 2010年11月19日 [査読無し][通常論文]
  
• 腹部エコーのブラッシュ・アップ―上腹部を極める―

  滝口満喜 動物臨床医学会年次大会プロシーディング 31st (1) 1 -1 2010年11月19日 [査読無し][通常論文]
  
• 消化器疾患の内科学的アプローチ―診断技術の向上と的確な治療を目指して―

  滝口満喜 動物臨床医学会年次大会プロシーディング 31st (3) 187 -187 2010年11月19日 [査読無し][通常論文]
  
• ガストリン産生性カルチノイドに対し徐放性オクトレオチド製剤を使用した犬の1例

  細谷 謙次, 金子 一成, 滝口 満喜, 中村 健介, 高木 哲, 奥村 正裕 動物臨床医学会年次大会プロシーディング 31回 (2) 193 -194 2010年11月 [査読無し][通常論文]
  
• “診る目を養う”超音波検査 第2回 黄疸を超音波で鑑別する(1)胆道系の超音波検査

  滝口満喜, 中村健介 SA Med 12 (5) 79 -85 2010年10月01日 [査読無し][通常論文]
  
• 教育の質保証と獣医学モデル・コア・カリキュラムおよび獣医学共用試験の役割 「eラーニングコンテンツ作成の試み」内科学

  滝口 満喜 日本獣医学会学術集会講演要旨集 150回 131 -131 2010年09月
• 微小気泡存在下での診断用超音波照射によるシスプラチンの抗腫瘍効果増強の検討

  佐々木 東, 中村 健介, 村上 正紘, Bandula Kumara, 田村 悠, 大田 寛, 山崎 真大, 工藤 信樹, 滝口 満喜 日本獣医学会学術集会講演要旨集 150回 297 -297 2010年09月 [査読無し][通常論文]
  
• 犬のガストリノーマに対してサンドスタチンLARを投与した1例

  金子 一成, 細谷 謙次, 滝口 満喜, 中村 健介, 北村 二郎, 高木 哲, 奥村 正裕 北海道獣医師会雑誌 54 (8) 450 -450 2010年08月 [査読無し][通常論文]
  
• “診る目を養う”超音波検査 第1回 腹部エコー:基本と上達のコツ

  滝口満喜 SA Med 12 (4) 67 -71 2010年08月01日 [査読無し][通常論文]
  
• 造影超音波検査により病変の特定が可能であったインスリノーマの犬2例

  中村 健介, 高木 哲, 山崎 真大, 大田 寛, 滝口 満喜 北海道獣医師会雑誌 54 (8) 460 -460 2010年08月 [査読無し][通常論文]
  
• 胆嚢粘液嚢腫の犬19症例の回顧的解析

  睦良田 尚充, 高木 哲, 細谷 謙次, 中村 健介, 大田 寛, 山崎 真大, 滝口 満喜, 佐藤 耕太, 奥村 正裕 北海道獣医師会雑誌 54 (8) 462 -462 2010年08月 [査読無し][通常論文]
  
• 細菌性心内膜炎の犬の1例

  森 伸介, 大田 寛, 境 秀文, 山崎 真大, 滝口 満喜 北海道獣医師会雑誌 54 (8) 459 -459 2010年08月 [査読無し][通常論文]
  
• 犬の皮膚無菌性肉芽腫/化膿性肉芽腫症候群と診断した1症例

  若木 望美, 山崎 真大, 大田 寛, 那須野 豊彦, 落合 謙爾, 竹林 賢作, 滝口 満喜 北海道獣医師会雑誌 54 (8) 464 -464 2010年08月 [査読無し][通常論文]
  
• リンパ管拡張症を疑う胸水貯留に続発して肺葉捻転を起こした犬の1例

  村上 正紘, 中村 健介, 佐々木 東, 大田 寛, 山崎 真大, 高木 哲, 滝口 満喜 北海道獣医師会雑誌 54 (8) 464 -464 2010年08月 [査読無し][通常論文]
  
• 造影3DCTにより確定診断し得た犬の重複大動脈弓の1例

  松山 新, 金子 一成, 山根 由久, 中村 健介, 大田 寛, 山崎 真大, 滝口 満喜 北海道獣医師会雑誌 54 (8) 458 -458 2010年08月 [査読無し][通常論文]
  
• 心房中隔欠損症と僧帽弁閉鎖不全症を併発した犬の1例

  小儀 直子, 中村 健介, 松山 新, 橋場 実, 大田 寛, 山崎 真大, 滝口 満喜 北海道獣医師会雑誌 54 (8) 458 -458 2010年08月 [査読無し][通常論文]
  
• 経皮的エコーガイド下胆嚢穿刺により確定診断した細菌性胆嚢炎の犬と猫の2例

  鵜飼 綾子, 金子 一成, 大川 美奈子, 大田 寛, 小林 秀明, 山崎 真大, 滝口 満喜 北海道獣医師会雑誌 54 (8) 461 -461 2010年08月 [査読無し][通常論文]
  
• 二次性赤血球増加症を伴ったEisenmenger症候群の犬に対するシルデナフィルの有効性の検討

  中村 健介, 山崎 真大, 大田 寛, 滝口 満喜 獣医麻酔外科学雑誌 41 (Suppl.1) 294 -294 2010年07月 [査読無し][通常論文]
  
• CONTRAST-ENHANCED ULTRASONOGRAPHY WITH SONAZOID (R) FOR CHARACTERIZATION OF FOCAL SPLENIC LESIONS

  K. Nakamura, H. Ohta, M. Yamasaki, M. Takiguchi JOURNAL OF VETERINARY INTERNAL MEDICINE 24 (3) 733 -734 2010年05月 [査読無し][通常論文]
  
• 培養Babesia gibsoniの末梢血単核球への侵入と増殖の検討

  谷山裕介, 山崎真大, HWANG Shiang‐Jyi, 大田寛, 滝口満喜 日本寄生虫学会大会プログラム・抄録集 79th 70 2010年05月 [査読無し][通常論文]
  
• ビジュアルで学ぶ!内視鏡検査と治療 第7回 手技編 下部消化管の内視鏡検査

  滝口満喜 MVM 19 (4) 68 -69 2010年05月01日 [査読無し][通常論文]
  
• 超音波診断装置と微小気泡によるシスプラチンの抗腫瘍効果の増強

  佐々木 東, 中村 健介, 村上 正紘, Kumara Bandula, 大田 寛, 山崎 真大, 工藤 信樹, 滝口 満喜 超音波医学 37 (Suppl.) S322 -S322 2010年04月 [査読無し][通常論文]
  
• Diminazene aceturate耐性Babesia gibsoni株に対する他の抗バベシア原虫薬の効果

  黄 香寂, 谷山 裕介, 山崎 真大, 大田 寛, 滝口 満喜 獣医寄生虫学会誌 8 (2) 149 -149 2010年03月 [査読無し][通常論文]
  
• イヌおよびネコの腎疾患における病態差 腎機能とスリット膜関連分子の動態

  市居 修, 矢吹 映, 佐々木 宣哉, 大田 寛, 滝口 満喜, 大塚 沙織, 橋本 善春, 遠藤 大二, 昆 泰寛 日本獣医学会学術集会講演要旨集 149回 213 -213 2010年03月 [査読無し][通常論文]
  
• 犬の肝臓腫瘤30例に対するソナゾイド造影超音波検査

  中村健介, 高木哲, 山崎真大, 大田寛, 佐々木東, 滝口満喜 日本獣医師会三学会年次大会講演要旨集 2009 237 2010年01月07日 [査読無し][通常論文]
  
• 診断と内科治療

  滝口満喜 獣医麻酔外科学雑誌 40 (Supplement 2) 99 -99 2009年12月10日 [査読無し][通常論文]
  
• 外科手術を実施した犬の肝細胞癌17症例の検討

  高木 哲, 滝口 満喜, 山崎 真大, 大田 寛, 中村 健介, 大崎 智弘, 細谷 謙次, 奥村 正裕 獣医麻酔外科学雑誌 40 (Suppl.2) 196 -196 2009年12月 [査読無し][通常論文]
  
• 犬の消化器疾患の内科学的アプローチ―最新の診断技術と治療法の紹介―

  滝口満喜 動物臨床医学会年次大会プロシーディング 30th (3) 247 -247 2009年11月20日 [査読無し][通常論文]
  
• 腹部エコー:基本と上達への道

  滝口満喜 動物臨床医学会年次大会プロシーディング 30th (1) 9 -9 2009年11月20日 [査読無し][通常論文]
  
• 犬のリンパ球プラズマ細胞性腸炎における細胞接着分子クローディンの発現変動

  大田 寛, 村上 正紘, Bandura Kumara, 佐々木 東, 中村 健介, 黄 香寂, 山埼 真大, 滝口 満喜 日本獣医学会学術集会講演要旨集 148回 261 -261 2009年09月 [査読無し][通常論文]
  
• Diminazene aceturate耐性Babesia gibsoni株に対する他の抗バベシア原虫薬の効果

  黄 香寂, 谷山 裕介, 山崎 真大, 大田 寛, 滝口 満喜 日本獣医学会学術集会講演要旨集 148回 188 -188 2009年09月 [査読無し][通常論文]
  
• 犬の脾臓腫瘤におけるソナゾイド造影超音波検査の有用性

  中村 健介, 山崎 真大, 大田 寛, 佐々木 東, 村上 正紘, 滝口 満喜 日本獣医学会学術集会講演要旨集 148回 268 -268 2009年09月 [査読無し][通常論文]
  
• 犬の肝臓腫瘤28結節に対するソナゾイド造影超音波検査

  中村 健介, 高木 哲, 佐々木 東, 村上 正紘, 大田 寛, 山崎 真大, 滝口 満喜 北海道獣医師会雑誌 53 (8) 101 -101 2009年08月 [査読無し][通常論文]
  
• 胆嚢粘液嚢腫の犬5例における周術期管理

  光田 健太, 高木 哲, 須永 隆文, 滝口 満喜, 大田 寛, 佐藤 耕太, 大崎 智弘, 奥村 正裕 北海道獣医師会雑誌 53 (8) 93 -93 2009年08月 [査読無し][通常論文]
  
• 大脳辺縁系の壊死が疑われた猫の1症例

  上條 弘美, 大田 寛, 松本 正憲, 山崎 真大, 滝口 満喜 北海道獣医師会雑誌 53 (8) 103 -103 2009年08月 [査読無し][通常論文]
  
• 筋炎の併発が疑われた劇症型重症筋無力症の犬の1例

  鵜飼 綾子, 芳川 宗義, 中村 健介, 大田 寛, 山崎 真大, 中尾 喜一, 滝口 満喜 北海道獣医師会雑誌 53 (8) 98 -98 2009年08月 [査読無し][通常論文]
  
• 消化器系の診療手技 消化管の超音波検査

  滝口満喜 SA Med 11 (4) 24 -33 2009年08月01日 [査読無し][通常論文]
  
• 本態性高Na血症が疑われた神経症状を示した犬と猫の2例

  村上 正紘, 大田 寛, 中村 健介, 佐々木 東, 山崎 真大, 江藤 正之, 小関 ユミ, 滝口 満喜 北海道獣医師会雑誌 53 (8) 97 -97 2009年08月 [査読無し][通常論文]
  
• 気管支内視鏡検査で気管支狭窄を認めた慢性発咳の犬の1症例

  佐々木 東, 大田 寛, 安藤 玲美, 中村 健介, 村上 正紘, 山崎 真大, 滝口 満喜 北海道獣医師会雑誌 53 (8) 88 -88 2009年08月 [査読無し][通常論文]
  
• ボストンテリアの脾臓捻転の1症例

  大田 寛, 高木 哲, 中澤 茂樹, 村上 正紘, 佐々木 東, 中村 健介, 山崎 真大, 滝口 満喜 北海道獣医師会雑誌 53 (8) 89 -89 2009年08月 [査読無し][通常論文]
  
• 腹部エコーの基礎とブラッシュ・アップ

  滝口満喜 獣医麻酔外科学雑誌 40 (Supplement 1) 150 -150 2009年06月20日 [査読無し][通常論文]
  
• 腎疾患の新しい診断指標 Interleukin 1 family、member 6は尿細管傷害マーカーになり得る

  市居 修, 昆 泰寛, 佐々木 宣哉, 橋本 善春, 大田 寛, 滝口 満喜, 矢吹 映, 遠藤 大二 日本獣医学会学術集会講演要旨集 147回 79 -79 2009年03月 [査読無し][通常論文]
  
• 培養Babesia gibsoniのストレス環境下におけるheat shock protein 70の役割に関する研究

  山崎真大, HWANG Shiang‐Jyi, 大田寛, 滝口満喜 日本寄生虫学会大会プログラム・抄録集 78th 86 2009年02月 [査読無し][通常論文]
  
• SLEが疑われた血球貪食症候群の猫の1例

  芳川宗義, 中村健介, 佐々木東, 大田寛, 山崎真大, 滝口満喜 日本獣医師会三学会年次大会講演要旨集 2008 296 2008年12月25日 [査読無し][通常論文]
  
• ポリエン系抗生物質アムホテリシンBの抗Babesia gibsoni効果

  原田 絵梨子, 山崎 真大, 黄 寂香, 大田 寛, 滝口 満喜 獣医寄生虫学会誌 7 (2) 90 -90 2008年12月 [査読無し][通常論文]
  
• Diminazene aceturate耐性Babesia gibsoni株の作成

  黄 香寂, 山崎 真大, 大田 寛, 滝口 満喜 獣医寄生虫学会誌 7 (2) 92 -92 2008年12月 [査読無し][通常論文]
  
• 初心者のための基本的な消化管の画像診断(X線,超音波,内視鏡)

  滝口満喜 動物臨床医学会年次大会プロシーディング 29th (1) 110 -110 2008年11月14日 [査読無し][通常論文]
  
• 簡便な犬リポ蛋白質の測定法の開発と臨床例への応用

  高崎 由香梨, 山崎 真大, 大田 寛, 滝口 満喜 動物臨床医学会年次大会プロシーディング 29回 (3) 37 -40 2008年11月 [査読無し][通常論文]
  
• 超音波検査により求めた正常なビーグル犬の甲状腺体積と体重の相関

  佐々木 東, 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 29回 (3) 29 -32 2008年11月 [査読無し][通常論文]
  
• 犬の肝臓における造影超音波検査の有用性の検討

  中村 健介, 佐々木 東, 芳川 宗義, 黄 香寂, 大田 寛, 山崎 真大, 滝口 満喜 日本獣医学会学術集会講演要旨集 146回 265 -265 2008年09月 [査読無し][通常論文]
  
• 犬の消化管粘膜におけるクローディン分子群の発現 十二指腸を中心として

  山口 朋生, 大田 寛, 中村 健介, 黄 香寂, 佐々木 東, 芳川 宗義, 山崎 真大, 滝口 満喜 日本獣医学会学術集会講演要旨集 146回 258 -258 2008年09月 [査読無し][通常論文]
  
• Diminazene aceturate耐性Babesia gibsoni株の作成

  黄 香寂, 山崎 真大, 大田 寛, 滝口 満喜 日本獣医学会学術集会講演要旨集 146回 173 -173 2008年09月 [査読無し][通常論文]
  
• ポリエン系抗生物質アムホテリシンBの抗Babesia gibsoni効果

  原田 絵梨子, 山崎 真大, 黄 香寂, 大田 寛, 滝口 満喜 日本獣医学会学術集会講演要旨集 146回 172 -172 2008年09月 [査読無し][通常論文]
  
• 抗リン脂質抗体症候群が疑われた不明熱のミニチュア・ダックスフンドの1例

  中村 健介, 佐々木 東, 芳川 宗義, 大田 寛, 山崎 真大, 大場 雅予, 滝口 満喜 北海道獣医師会雑誌 52 (8) 410 -410 2008年08月 [査読無し][通常論文]
  
• 犬の無菌性好酸球性膿疱症と診断した2症例

  南山 依里, 山崎 真大, 大田 寛, 本田 英隆, 那須野 豊彦, 落合 謙爾, 滝口 満喜 北海道獣医師会雑誌 52 (8) 413 -413 2008年08月 [査読無し][通常論文]
  
• 気胸を併発した先天性肺葉性肺気腫の犬の1例

  上條 弘美, 高木 哲, 大田 寛, 山崎 真大, 木村 享史, 滝口 満喜 北海道獣医師会雑誌 52 (8) 420 -420 2008年08月 [査読無し][通常論文]
  
• エリスロポエチン依存性の二次性多血症が疑われた腎リンパ腫の犬の1例

  佐々木 東, 芳川 宗義, 中村 健介, 大田 寛, 山崎 真大, 佐藤 耕太, 滝口 満喜 北海道獣医師会雑誌 52 (8) 415 -415 2008年08月 [査読無し][通常論文]
  
• SLEが疑われた血球貪食症候群の猫の1例

  芳川 宗義, 庄田 雅人, 中村 健介, 佐々木 東, 大田 寛, 山崎 真大, 滝口 満喜 北海道獣医師会雑誌 52 (8) 410 -410 2008年08月 [査読無し][通常論文]
  
• 犬の炎症性腸疾患 リンパ球形質細胞性腸炎・結腸炎を中心に

  大田 寛, 山崎 真大, 滝口 満喜 北海道獣医師会雑誌 52 (7) 263 -265 2008年07月 [査読無し][通常論文]
  
• 第二世代超音波造影剤ソナゾイドによる肝臓腫瘤の診断

  中村 健介, 大田 寛, 山崎 真大, 滝口 満喜 獣医麻酔外科学雑誌 39 (Suppl.1) 227 -227 2008年06月 [査読無し][通常論文]
  
• 腹部エコー検査のススメ―小動物臨床における超音波造影剤の可能性

  中村健介, 滝口満喜 CAP (Companion Anim Pract) 23 (225) 23 -28 2008年03月01日 [査読無し][通常論文]
  
• クエン酸シルデナフィルが奏功した逆行性動脈管開存症のイヌの2例

  中村健介, 森下啓太郎, 中出哲也, 滝口満喜 日本獣医師会三学会年次大会講演要旨集 2007 245 2008年 [査読無し][通常論文]
  
• 第二世代超音波造影剤ソナゾイドの小動物臨床への応用に関する基礎的検討

  滝口満喜, 中村健介 獣医麻酔外科学雑誌 38 (Supplement 2) 290 -291 2007年11月20日 [査読無し][通常論文]
  
• 犬の膵疾患における超音波ヒストグラム解析の有用性に関する基礎的研究

  中村健介, 森下啓太郎, 滝口満喜 日本獣医学会学術集会講演要旨集 144th 160 -160 2007年08月27日 [査読無し][通常論文]
  
• クエン酸シルデナフィルが奏功した逆行性動脈管開存症の犬の2例

  中村健介, 森下啓太郎, 中出哲也, 滝口満喜 北海道獣医師会雑誌 51 (8) 333 -333 2007年08月01日 [査読無し][通常論文]
  
• メソトレキセートが奏功したステロイド抵抗性炎症性腸疾患の犬の1例

  森下啓太郎, 中村健介, 平山和子, 谷山弘行, 滝口満喜 北海道獣医師会雑誌 51 (8) 335 -335 2007年08月01日 [査読無し][通常論文]
  
• デジタルX線(DR)撮影下における非選択的血管造影法により逆行性動脈管開存症と診断された犬の2例

  森下啓太郎, 中村健介, 中出哲也, 滝口満喜 日本獣医循環器学会抄録 86th (Suppl.1) 203 -203 2007年 [査読無し][通常論文]
  
• 十二指腸に閉塞性病変を伴った炎症性陽疾患の犬の1例

  中村 健介, 森下 啓太郎, 廉澤 剛, 平山 和子, 谷山 弘行, 滝口 満喜 北海道獣医師会雑誌 50 (8) 79 -79 2006年08月
• I型偽性低アルドステロン症が疑われた犬の1例

  森下啓太郎, 中村健介, 滝口満喜 北海道獣医師会雑誌 50 (8) 336 -80 2006年08月01日 [査読無し][通常論文]
  
• 犬の慢性リンパ性白血病:メルファラン継続投与による良好な長期コントロールの1例

  廣瀬武士, 中村健介, 森下啓太郎, 滝口満喜 北海道獣医師会雑誌 50 (8) 346 -90 2006年08月01日 [査読無し][通常論文]
  
• デジタルX線(DR)撮影下における非選択的血管造影法により逆行性動脈管開存症と診断された犬の1例

  遠山伸夫, 中村健介, 森下啓太郎, 中出哲也, 滝口満喜 北海道獣医師会雑誌 50 (8) 355 -99 2006年08月01日 [査読無し][通常論文]
  
• 十二指腸に閉塞性病変を伴った炎症性腸疾患の犬の1例

  中村健介, 森下啓太郎, 廉澤剛, 平山和子, 谷山弘行, 滝口満喜 北海道獣医師会雑誌 50 (8) 335 2006年08月01日 [査読無し][通常論文]
  
• 肉芽腫性胃炎により幽門狭窄症を呈したイヌの一例

  中村健介, 滝口満喜 獣医麻酔外科学雑誌 37 (Supplement 1) 207 -207 2006年06月20日 [査読無し][通常論文]
  
• 壊死性髄膜脳炎(NME)が強く疑われた犬8例と抗アストロサイト抗体

  中出哲也, 松木直章, 井上愛香, 滝口満喜, 新山雅美, 泉沢康晴, 棚田敦司, 吉岡祐, 吉岡飛夏, 渡辺拓夫, 寺沢元子, 柄本浩一, 石塚希征子, 玉井聡 動物臨床医学会年次大会プロシーディング 26th (2) 195 -196 2005年11月18日 [査読無し][通常論文]
  
• 臨床的に線維軟骨性塞栓症と診断されたイヌのMRI所見

  三好健二郎, 中出哲也, 泉沢康晴, 滝口満喜 動物臨床医学会年次大会プロシーディング 26th (3) 26 -29 2005年11月18日 [査読無し][通常論文]
  
• 食道狭窄:とくに猫,バルーンなどを使った治療

  滝口満喜 獣医麻酔外科学雑誌 36 (Supplement 2) 73 -73 2005年10月01日 [査読無し][通常論文]
  
• 私立および国立獣医大学における臨床講座の違いとそれぞれの教育・研究のあり方

  滝口満喜 日本獣医学会学術集会講演要旨集 140th 30 -30 2005年08月31日 [査読無し][通常論文]
  
• 犬の明らかな血小板増多を伴った赤芽球癆

  町田 竜彦, 内田 英二, 伊藤 真之, 木村 真, 滝口 満喜, 谷山 弘行 北海道獣医師会雑誌 49 (8) 71 -71 2005年08月
• 眼底出血から副腎腫瘍が疑われた犬の1例

  若生 晋輔, 滝口 満喜, 前原 誠也, 久保 明, 都築 圭子, 伊藤 典彦, 泉澤 康晴 北海道獣医師会雑誌 49 (8) 73 -73 2005年08月
• 犬猫の消化管内異物の超音波診断

  滝口満喜 獣医画像診断 (16/17) 3 -8 2005年08月 [査読無し][通常論文]
  
• 眼底出血から副腎腫ようが疑われた犬の1例

  若生晋輔, 滝口満喜, 前原誠也, 久保明, 都築圭子, 伊藤典彦, 泉沢康晴 北海道獣医師会雑誌 49 (8) 289 2005年08月01日 [査読無し][通常論文]
  
• 頻回の内視鏡下バルーン拡張術が功を奏した食道狭窄の猫の1例

  三輪絵里子, 宮田佳代子, 町田竜彦, 中村健介, 中出哲也, 滝口満喜 北海道獣医師会雑誌 49 (8) 276 -60 2005年08月01日 [査読無し][通常論文]
  
• 犬の明らかな血小板増多を伴った赤芽球ろう

  町田竜彦, 内田英二, 伊藤真之, 木村真, 滝口満喜, 谷山弘行 北海道獣医師会雑誌 49 (8) 287 2005年08月01日 [査読無し][通常論文]
  
• 超音波検査により粥状動脈硬化症と診断された犬の1例

  中村健介, 北村二郎, 滝口満喜 北海道獣医師会雑誌 49 (8) 293 -77 2005年08月01日 [査読無し][通常論文]
  
• 血管超音波検査によりアテローム性動脈硬化症が疑われた犬の一例

  中村 健介, 北村 二郎, 滝口 満喜 日本獣医循環器学会抄録 82 249 -249 2005年06月25日
• 最近の腹部超音波診断の有効性

  滝口満喜 獣医麻酔外科学雑誌 36 (Supplement 1) 120 -120 2005年06月20日 [査読無し][通常論文]
  
• 血管超音波検査によりアテローム性動脈硬化症が疑われた犬の一例

  中村健介, 北村二郎, 滝口満喜 獣医麻酔外科学雑誌 36 (Supplement 1) 240 -240 2005年06月20日 [査読無し][通常論文]
  
• Autoimmunity against a tissue kallikrein in IQI/Jic mice - A model for Sjogren's syndrome

  K Takada, M Takiguchi, A Konno, A Inaba JOURNAL OF BIOLOGICAL CHEMISTRY 280 (5) 3982 -3988 2005年02月 [査読無し][通常論文]
   

  We have recently characterized IQI/Jic mice as a model for Sjogren's syndrome (SS), a chronic autoimmune disease in humans. In SS, local lymphocytic infiltrations into salivary and lacrimal glands frequently develop to the involvement of systemic exocrine and nonexocrine organs, and the mechanism for progression of this disease remains obscure. Herein, we report identification of an autoantigen shared by various target organs in IQI/Jic mice. Polypeptides identified based on immunorecognition by autoantibodies in sera from IQI/ Jic mice affected with autoimmune disease (> 12 weeks of age) were tissue kallikrein (Klk)-1 and -13 and were cross-reactive to the autoantibodies. Interestingly, Klk-13, but not Klk-1, caused a proliferative response of splenic T cells from IQI/Jic mice from the age of 4 weeks onward. In addition, remarkably enhanced expression of Klk-13 was observed in the salivary glands of the mice in accordance with the development of inflammatory lesions. These results indicate that Klk-13 acts as an autoantigen and may increase T cells responsive to organs commonly expressing Klk-13, playing a pivotal role in the etiology of progression of disease in IQI/Jic mice. Our findings provide insights into the contributions of autoantigens shared by multiple organs in the progress of SS from an organ-specific to a systemic disorder.
• 紐状異物による十二指腸の穿孔に対して腸管内側から修復を行った犬の1例

  星野有希, 廉沢剛, 滝口満喜, 奥村正裕, 藤永徹 獣医麻酔外科学雑誌 36 (1) 19 -22 2005年01月31日 [査読無し][通常論文]
  
• 犬のポリープ様ぼうこう炎の超音波画像所見

  滝口満喜 日本産業動物獣医学会・日本小動物獣医学会・日本獣医公衆衛生学会年次大会 2004 295 2005年 [査読無し][通常論文]
  
• 胸部,腹部の超音波診断法

  滝口満喜 日本産業動物獣医学会・日本小動物獣医学会・日本獣医公衆衛生学会年次大会 2004 212 -215 2005年 [査読無し][通常論文]
  
• 腎臓の障害をいかにして知るか―腎疾患の画像診断―

  滝口満喜 動物臨床医学会年次大会プロシーディング 25th (1) 326 -326 2004年11月19日 [査読無し][通常論文]
  
• 犬と猫の急性すい炎のすべてがわかるセミナー―急性すい炎の画像診断―

  滝口満喜 動物臨床医学会年次大会プロシーディング 25th (3) 240 -241 2004年11月19日 [査読無し][通常論文]
  
• 脳溢血と診断した小型初老犬の1例

  天内 満雄, 滝口 満喜, 黒田 敏 北海道獣医師会雑誌 48 (10) 4 -6 2004年10月
• IVRによりコイル栓塞術を実施したイヌ動脈管開存症の1例

  中出哲也, 廉沢剛, 滝口満喜, 浅野和之 獣医麻酔外科学雑誌 35 (Supplement 2) 61 -61 2004年10月01日 [査読無し][通常論文]
  
• 脳溢血と診断した小型初老犬の1例

  天内満雄, 滝口満喜, 黒田敏 北海道獣医師会雑誌 48 (10) 422 -424 2004年10月01日 [査読無し][通常論文]
  
• リパーゼ産生性すい臓腫ようによる無菌性脂肪織炎が疑われた犬の1例

  関口道子, 滝口満喜, 稲葉睦 北海道獣医師会雑誌 48 (8) 305 -305 2004年08月01日 [査読無し][通常論文]
  
• ホジキン型リンパ腫が疑われた猫の1例

  岡崎和子, 滝口満喜, 木村享史, 松田英一郎, 稲葉睦 北海道獣医師会雑誌 48 (8) 319 -319 2004年08月01日 [査読無し][通常論文]
  
• 新生子牛のグロビンスイッチングにおける転写因子erythroid Kruppel‐like factorの役割

  新敷信人, 伊東大介, 滝口満喜, 稲葉睦 日本獣医学会学術集会講演要旨集 138th 148 -148 2004年08月01日 [査読無し][通常論文]
  
• 反芻動物赤血球膜タンパク質gp155の分子実態はMRP4である

  平井 真弓, 伊東 大介, 大田 寛, 滝口 満喜, 稲葉 睦 日本獣医学会学術集会講演要旨集 138回 178 -178 2004年08月 [査読無し][通常論文]
  
• クローディン-16欠損牛胎子腎の組織構築とタイトジャンクション構成分子の発現動態

  大田 寛, 伊東 大介, 陰山 聡一, 平山 博樹, 滝口 満喜, 稲葉 睦 日本獣医学会学術集会講演要旨集 138回 148 -148 2004年08月 [査読無し][通常論文]
  
• 血尿を主訴とした雌ウサギの子宮疾患例

  永野昌志, 片桐成二, 滝口満喜, 小松智彦, 永島太郎, 井川真一, 高橋芳幸 北海道獣医師会雑誌 48 (8) 318 -318 2004年08月01日 [査読無し][通常論文]
  
• 犬のポリープ様ぼうこう炎の超音波画像

  滝口満喜, 稲葉睦 北海道獣医師会雑誌 48 (8) 307 -307 2004年08月01日 [査読無し][通常論文]
  
• シェーグレン症候群モデルマウス・IQI/Jicにおける自己抗原の同定

  高田健介, 滝口満喜, 稲葉睦 日本獣医学会学術集会講演要旨集 138th 160 -160 2004年08月01日 [査読無し][通常論文]
  
• バンド3の細胞膜移行におけるC末端細胞質領域の重要性

  伊東 大介, 大田 寛, 滝口 満喜, 稲葉 睦 日本獣医学会学術集会講演要旨集 138回 178 -178 2004年08月 [査読無し][通常論文]
  
• Spontaneous development of multiple glandular and extra-glandularlesions in aged IQI/Jic mice: a model for primary Sjögren's syndrome 'jointly worked'

  K Takada, M Takiguchi, A Konno, M Inaba Reumatology 43 (7) 858 -862 2004年07月 [査読無し][通常論文]
   

  Objective. In primary Sjogren's syndrome (SS), systemic exocrine and non-exocrine organs are frequently affected, in addition to the major target tissues of the lacrimal and salivary glands. This study aimed to examine whether the IQI/Jic mouse, an animal model of SS whose autoimmune dacryoadenitis and sialoadenitis have been documented, develops inflammatory lesions in multiple organs as in primary SS. Methods. Systemic histopathological analysis was performed on IQI/Jic mice at various ages. Phenotypes of infiltrated lymphocytes were determined using immunohistochemical techniques. Results. Inflammatory lesions were observed not only in the lacrimal and salivary glands, but also in multiple organs, including the lung, pancreas and kidney at advanced ages, and were mainly composed of CD4(+) T cells and B cells. The incidence and severity of the inflammatory lesions increased with age in all these organs. The histological appearance and spreading of lesions were similar to those in human primary SS. Conclusions. IQI/Jic mice spontaneously develop inflammatory cellular infiltrates in multiple exocrine and non-exocrine organs. This characteristic distinguishes IQI/Jic mice from other murine models, making them favourable for studies on the pathogenesis of systemic involvement in primary SS.
• Spontaneous development of multiple glandular and extraglandular lesions in aged IQI/Jic mice: a model for primary Sjogren's syndrome

  K Takada, M Takiguchi, A Konno, M Inaba RHEUMATOLOGY 43 (7) 858 -862 2004年07月 [査読無し][通常論文]
   

  Objective. In primary Sjogren's syndrome (SS), systemic exocrine and non-exocrine organs are frequently affected, in addition to the major target tissues of the lacrimal and salivary glands. This study aimed to examine whether the IQI/Jic mouse, an animal model of SS whose autoimmune dacryoadenitis and sialoadenitis have been documented, develops inflammatory lesions in multiple organs as in primary SS. Methods. Systemic histopathological analysis was performed on IQI/Jic mice at various ages. Phenotypes of infiltrated lymphocytes were determined using immunohistochemical techniques. Results. Inflammatory lesions were observed not only in the lacrimal and salivary glands, but also in multiple organs, including the lung, pancreas and kidney at advanced ages, and were mainly composed of CD4(+) T cells and B cells. The incidence and severity of the inflammatory lesions increased with age in all these organs. The histological appearance and spreading of lesions were similar to those in human primary SS. Conclusions. IQI/Jic mice spontaneously develop inflammatory cellular infiltrates in multiple exocrine and non-exocrine organs. This characteristic distinguishes IQI/Jic mice from other murine models, making them favourable for studies on the pathogenesis of systemic involvement in primary SS.
• 乳腺上皮細胞におけるタイトジャンクション構成タンパク質の発現動態

  大田寛, 駒林賢一, 伊東大介, 滝口満喜, 稲葉睦 日本膜学会年会講演要旨集 26th 56 2004年04月30日 [査読無し][通常論文]
  
• 牛遺伝性バンド3欠損症ホモ接合型胎子における組織病態

  伊東 大介, 陰山 聡一, 澤井 健, 永田 暁洋, 大田 寛, 滝口 満喜, 伴 顕, 渡辺 大作, 稲葉 睦 日本獣医学会学術集会講演要旨集 137回 136 -136 2004年03月 [査読無し][通常論文]
  
• 乳腺管腔上皮におけるタイトジャンクション構成蛋白質の発現動態

  大田 寛, 駒林 賢一, 伊東 大介, 渡辺 淳, 滝口 満喜, 稲葉 睦 日本獣医学会学術集会講演要旨集 137回 152 -152 2004年03月 [査読無し][通常論文]
  
• Autoimmunity against a tissue kallikrein in IQI/Jic mice, a model for Sjogren's syndrome 'jointly worked'

  J. Biol. Chem.. (in press) 2004年 [査読無し][通常論文]
  
• Diagnostic ultrasound of polypoid cystitis in the dog 'jointly worked'

  J. Vet. Med. Sci. (in press) 2004年 [査読無し][通常論文]
  
• Diagnostic ultrasound of polypoid cystitis in the dog 'jointly worked'

  J. Vet. Med. Sci. (in press) 2004年 [査読無し][通常論文]
  
• 腎疾患の新たな診断と治療法を目指して 腎疾患の画像診断

  滝口満喜 獣医畜産新報 57 (990) 35 -40 2004年01月01日 [査読無し][通常論文]
  
• Magnetic resonance imaging and immunoblot analyses in rats with experimentally induced cerebral alveolar echinococcosis

  T Asanuma, Y Matsumoto, M Takiguchi, O Inanami, M Nakao, K Nakaya, A Ito, A Hashimoto, M Kuwabara COMPARATIVE MEDICINE 53 (6) 649 -656 2003年12月 [査読無し][通常論文]
   

  The early stage of experimentally induced secondary cerebral alveolar echinococcosis (AE) in rats was investigated by use of magnetic resonance imaging (MRI) and immunoblot (western blot) analyses. Thirty-six female Wistar rats (6 to 8 weeks old) were injected intracranially with a 10% homogenate of echinococcal larval tissues in which the concentrations of microvesicles and protoscolices were estimated to be 3.8 and 1.5 x 10(4)/ml, respectively. To observe the fine structure of the rat brain, MRI was performed under a high magnetic field of 7.05 T. Histologic examination also was performed. The T2-weighted MR images revealed a hyperintense region in the cerebral cortex at two weeks after injection of the homogenate. At three weeks after injection, this region was found to have cysts on the basis of results of histologic examination. Signal-void regions corresponding to hyperplasia and the subsequent calcification of the cuticle layer at six and 13 weeks after injection, respectively, were observed in T2-weighted and proton density MR images. On the other hand, at nine weeks after injection, AE was discernible by use of western blot analysis of sera with antibodies of two epitopes (Em18 and Em16) of E. multilocularis. Using this secondary cerebral AE animal model, it was concluded that the MRI method was suitable for early detection of secondary cerebral AE.
• Magnetic resonance imaging and immunoblot analyses in rats with experimentally induced cerebral alveolar echinococcosis

  T Asanuma, Y Matsumoto, M Takiguchi, O Inanami, M Nakao, K Nakaya, A Ito, A Hashimoto, M Kuwabara COMPARATIVE MEDICINE 53 (6) 649 -656 2003年12月 [査読無し][通常論文]
   

  The early stage of experimentally induced secondary cerebral alveolar echinococcosis (AE) in rats was investigated by use of magnetic resonance imaging (MRI) and immunoblot (western blot) analyses. Thirty-six female Wistar rats (6 to 8 weeks old) were injected intracranially with a 10% homogenate of echinococcal larval tissues in which the concentrations of microvesicles and protoscolices were estimated to be 3.8 and 1.5 x 10(4)/ml, respectively. To observe the fine structure of the rat brain, MRI was performed under a high magnetic field of 7.05 T. Histologic examination also was performed. The T2-weighted MR images revealed a hyperintense region in the cerebral cortex at two weeks after injection of the homogenate. At three weeks after injection, this region was found to have cysts on the basis of results of histologic examination. Signal-void regions corresponding to hyperplasia and the subsequent calcification of the cuticle layer at six and 13 weeks after injection, respectively, were observed in T2-weighted and proton density MR images. On the other hand, at nine weeks after injection, AE was discernible by use of western blot analysis of sera with antibodies of two epitopes (Em18 and Em16) of E. multilocularis. Using this secondary cerebral AE animal model, it was concluded that the MRI method was suitable for early detection of secondary cerebral AE.
• Feline leptin: Immunogenic and biological activities of the recombinant protein, and its measurement by ELISA

  H Shibata, N Sasaki, T Honjoh, Ohishi, I, M Takiguchi, K Ishioka, M Ahmed, M Soliman, K Kimura, M Saito JOURNAL OF VETERINARY MEDICAL SCIENCE 65 (11) 1207 -1211 2003年11月 [査読無し][通常論文]
   

  Leptin is a protein synthesized and secreted primarily by adipose tissue. The blood leptin concentration is known to reflect body fat content in rodents, humans and dogs, and thereby is useful for quantitative assessment of obesity. In the present study, we produced recombinant feline leptin in Escherichia coli transfected with feline leptin cDNA we cloned previously. The recombinant feline leptin with a molecular weight of 16 kDa induced phosphorylation of the signal transducers and activators of transcription 3 (STAT3) protein in the cells expressing rat leptin receptor. The anti-feline leptin antibody raised in rabbits reacted well to feline and human leptin and less to rodents' leptin in Western blot analysis. Sandwich enzyme-linked immunosorbent assay (ELISA) was developed, using rabbit anti-feline leptin antibody and recombinant feline leptin as a standard. In this ELISA system, cross-reactivity to human, rat and mouse leptin was 30.7%, 69.5% and 66.6%, respectively. The plasma leptin levels of 24 healthy cats were in a range from 0.3 to 29.7 ng/ml with the mean +/- SEM of 4.5 +/- 1.3 ng/ml, being positively proportional to body fat content. These results indicate that our ELISA system may be useful for assessment of obesity in cats.
• Feline leptin: Immunogenic and biological activities of the recombinant protein, and its measurement by ELISA

  H Shibata, N Sasaki, T Honjoh, Ohishi, I, M Takiguchi, K Ishioka, M Ahmed, M Soliman, K Kimura, M Saito JOURNAL OF VETERINARY MEDICAL SCIENCE 65 (11) 1207 -1211 2003年11月 [査読無し][通常論文]
   

  Leptin is a protein synthesized and secreted primarily by adipose tissue. The blood leptin concentration is known to reflect body fat content in rodents, humans and dogs, and thereby is useful for quantitative assessment of obesity. In the present study, we produced recombinant feline leptin in Escherichia coli transfected with feline leptin cDNA we cloned previously. The recombinant feline leptin with a molecular weight of 16 kDa induced phosphorylation of the signal transducers and activators of transcription 3 (STAT3) protein in the cells expressing rat leptin receptor. The anti-feline leptin antibody raised in rabbits reacted well to feline and human leptin and less to rodents' leptin in Western blot analysis. Sandwich enzyme-linked immunosorbent assay (ELISA) was developed, using rabbit anti-feline leptin antibody and recombinant feline leptin as a standard. In this ELISA system, cross-reactivity to human, rat and mouse leptin was 30.7%, 69.5% and 66.6%, respectively. The plasma leptin levels of 24 healthy cats were in a range from 0.3 to 29.7 ng/ml with the mean +/- SEM of 4.5 +/- 1.3 ng/ml, being positively proportional to body fat content. These results indicate that our ELISA system may be useful for assessment of obesity in cats.
• 紐状異物による十二指腸の線状穿孔に対して腸管内側から修復を行った犬の一例

  星野有希, 廉沢剛, 滝口満喜, 松久祐貴, 奥村正裕, 藤永徹 獣医麻酔外科学雑誌 34 (Supplement 2) 99 -100 2003年09月20日 [査読無し][通常論文]
  
• 調節帯異常により左室機能障害を呈した猫の超音波検査

  浜本耕平, 滝口満喜, 稲葉睦 日本獣医学会学術集会講演要旨集 136th 205 -205 2003年09月10日 [査読無し][通常論文]
  
• シェーグレン症候群モデルマウス・IQI/Jicにおける多発性自己免疫病変の組織学的解析および自己抗原の同定

  高田健介, 滝口満喜, 稲葉睦 日本獣医学会学術集会講演要旨集 136th 218 -218 2003年09月10日 [査読無し][通常論文]
  
• 副腎性性ホルモン機能こう進症とポメラニアンの脱毛症X

  滝口満喜, 高田健介 日本獣医学会学術集会講演要旨集 136th 54 -54 2003年09月10日 [査読無し][通常論文]
  
• 腎疾患の画像診断

  滝口満喜 日本獣医学会学術集会講演要旨集 136th 50 -50 2003年09月10日 [査読無し][通常論文]
  
• 牛腎尿細管においてクローディン16と共存するパートナークローディンの解析と遺伝子の単離

  大田 寛, 伊東 大介, 駒林 賢一, 滝口 満喜, 稲葉 睦 日本獣医学会学術集会講演要旨集 136回 196 -196 2003年09月 [査読無し][通常論文]
  
• バンド3欠損症変異バンド3認識・分解の分子機構 R664X変異周辺領域認識の検証

  伊東 大介, 大田 寛, 滝口 満喜, 稲葉 睦 日本獣医学会学術集会講演要旨集 136回 217 -217 2003年09月 [査読無し][通常論文]
  
• 右大動脈弓遺残と動脈管開存が併発した犬の1例

  河村貴央, 滝口満喜, 浜本耕平, 長谷部理絵, 廉沢剛, 稲葉睦 北海道獣医師会雑誌 47 (8) 316 -316 2003年08月01日 [査読無し][通常論文]
  
• 甲状腺ホルモン製剤補充療法により病態が改善された拡張型心筋症の犬の1例

  岡崎和子, 滝口満喜, 浜本耕平, 村岡暢嘉, 稲葉睦 北海道獣医師会雑誌 47 (8) 295 -295 2003年08月01日 [査読無し][通常論文]
  
• 超音波検査によりしん出性収縮性心膜炎と診断された犬の1例

  浜本耕平, 滝口満喜, 伊藤啓, 木村享史, 廉沢剛, 稲葉睦 北海道獣医師会雑誌 47 (8) 315 -315 2003年08月01日 [査読無し][通常論文]
  
• 小動物の紐状異物の超音波画像診断

  滝口満喜, 浜本耕平, 稲葉睦 北海道獣医師会雑誌 47 (8) 317 -317 2003年08月01日 [査読無し][通常論文]
  
• 悪性組織球症が疑われた犬の2例

  伊藤啓, 滝口満喜, 浜本耕平, 中尾喜一, 稲葉睦 北海道獣医師会雑誌 47 (8) 291 -291 2003年08月01日 [査読無し][通常論文]
  
• 無菌性結節性脂肪織炎が疑われた犬の2例

  関口道子, 滝口満喜, 稲葉睦 北海道獣医師会雑誌 47 (8) 302 -302 2003年08月01日 [査読無し][通常論文]
  
• Presence of B7-2+ dendritic cells and expression of Th1 cytokines in the early development of sialodacryoadenitis in the IQI/Jic mouse model of primary Sjogren’s syndrome.

  A Konno, K Takada, J Saegusa, M Takiguchi Autoimmunity 36 (4) 247 -254 2003年07月 [査読無し][通常論文]
   

  Subpopulations of infiltrating lymphocytes, professional antigen-presenting cells (APCs), and Th1/Th2 cytokines that could initiate an autoimmune sialodacryoadenitis were studied in the IQI/Jic mouse model of primary Sjogren's syndrome. Although lymphocytic infiltrations were first seen in submandibular glands (SMGs) of females and in lacrimal glands (LGs) of males at 8 weeks of age, clusters of MHC class II+ , CD11c(+) , B7-2(+) dendritic cells (DCs) were already localized in these tissues at 4 weeks. At 8 weeks, the infiltrating lymphocytes consisted of almost equal numbers of B cells and CD4(+) T cells. In the inflammatory foci, MHC class II+ , CD11c(+) , B7-2(+) DCs formed network-like structures. Duct cells in the lesions showed immunoreactivities for MHC class II and ALCAM (a costimulatory adhesion molecule). IL-12 and IFN-gamma transcripts were detected by RT-PCR in SMGs of females and in LGs of males at 8-12 weeks. These results suggest that the clustered DCs might play an important role in the initiation of the adenitis, and further suggest that the DCs and epithelial cells may participate in the activation of CD4(+) T cells. It is also likely that Th1 cytokines mediate the functional interactions between the APCs and CD4(+) T cells in the early lesions.
• Presence of B7-2(+) dendritic cells and expression of Th1 cytokines in the early development of sialodacryoadenitis in the IQI/Jic mouse model of primary Sjogren's syndrome

  A Konno, K Takada, J Saegusa, M Takiguchi AUTOIMMUNITY 36 (4) 247 -254 2003年07月 [査読無し][通常論文]
   

  Subpopulations of infiltrating lymphocytes, professional antigen-presenting cells (APCs), and Th1/Th2 cytokines that could initiate an autoimmune sialodacryoadenitis were studied in the IQI/Jic mouse model of primary Sjogren's syndrome. Although lymphocytic infiltrations were first seen in submandibular glands (SMGs) of females and in lacrimal glands (LGs) of males at 8 weeks of age, clusters of MHC class II+ , CD11c(+) , B7-2(+) dendritic cells (DCs) were already localized in these tissues at 4 weeks. At 8 weeks, the infiltrating lymphocytes consisted of almost equal numbers of B cells and CD4(+) T cells. In the inflammatory foci, MHC class II+ , CD11c(+) , B7-2(+) DCs formed network-like structures. Duct cells in the lesions showed immunoreactivities for MHC class II and ALCAM (a costimulatory adhesion molecule). IL-12 and IFN-gamma transcripts were detected by RT-PCR in SMGs of females and in LGs of males at 8-12 weeks. These results suggest that the clustered DCs might play an important role in the initiation of the adenitis, and further suggest that the DCs and epithelial cells may participate in the activation of CD4(+) T cells. It is also likely that Th1 cytokines mediate the functional interactions between the APCs and CD4(+) T cells in the early lesions.
• 超音波検査を過小評価してはいないか?

  滝口満喜 日本獣医循環器学会抄録 78th 126 -126 2003年06月21日 [査読無し][通常論文]
  
• 最新の画像診断装置の獣医臨床応用の可能性‐超音波検査を過小評価してはいないか?

  滝口満喜 獣医麻酔外科学雑誌 34 (Supplement 1) 140 -140 2003年06月10日 [査読無し][通常論文]
  
• Moderator band cardiomyopathyを疑った猫の一例

  濱本 耕平, 滝口 満喜, 古橋 由美子, 高橋 徹 日本獣医循環器学会抄録 78回 210 -211 2003年06月
• イヌ脱毛症Xの原因候補遺伝子:21-ヒドロキシラーゼ遺伝子のクローニングと多型解析

  高田健介, 北村浩, 滝口満喜, 斉藤昌之, 橋本晃, 稲葉睦 獣医生化学 40 (1) 21 -27 2003年04月30日 [査読無し][通常論文]
  
• イヌ脱毛症Xの原因候補遺伝子：21-ヒドロキシラーゼ遺伝子のクローニングと多型解析（共著）

  獣医生化学 40(1): 21-27 2003年 [査読無し][通常論文]
  
• 犬の消化管内異物の超音波画像診断

  Small Animal Clinic 133: 22-25 2003年 [査読無し][通常論文]
  
• Cloning of canine 21-hydroxylase gene and its polymorphic analysis as a candidate gene for congenital adrenal hyperplasia-like syndrome in Pomeranians

  K Takada, H Kitamura, M Takiguchi, M Saito, A Hashimoto RESEARCH IN VETERINARY SCIENCE 73 (2) 159 -163 2002年10月 [査読無し][通常論文]
   

  A Strong breed predisposition to canine congenital adrenal hyperplasia-like syndrome (CAH-LS) exists and implies there is an hereditary cause. Pomeranians, one of the most predisposed breeds, have been reported to have partial adrenal dysfunction that could be associated with the pathogenesis of CAH-LS. In this study, the full-length complementary DNA (CDNA) of canine 21-OH, whose mutations are most likely responsible for the adrenal dysfunction in Pomeranians, was initially obtained from adrenal gland RNA by reverse transcription-polymerase chain reaction (RT-PCR), and its nucleotide sequence was determined. Genomic DNA samples from 16 Pomeranians and 30 control dogs, of seven different breeds, were tested for 21-OH gene polymorphisms by direct sequencing. No mutations affecting the primary structure and the transcriptional level of the 21-OH enzyme were found in Pomeranians. Our results indicate that the adrenal dysfunction in Pomeranians is not due to mutations of the 21-OH gene. This contrasts with the human form of CAH where 21-OH gene mutations are the major cause of the disease. (C) 2002 Elsevier Science Ltd. All rights reserved.
• Cloning of canine 21-hydroxylase gene and its polymorphic analysis as a candidate gene for congenital adrenal hyperplasia-like syndrome in Pomeranians

  K Takada, H Kitamura, M Takiguchi, M Saito, A Hashimoto RESEARCH IN VETERINARY SCIENCE 73 (2) 159 -163 2002年10月 [査読無し][通常論文]
   

  A Strong breed predisposition to canine congenital adrenal hyperplasia-like syndrome (CAH-LS) exists and implies there is an hereditary cause. Pomeranians, one of the most predisposed breeds, have been reported to have partial adrenal dysfunction that could be associated with the pathogenesis of CAH-LS. In this study, the full-length complementary DNA (CDNA) of canine 21-OH, whose mutations are most likely responsible for the adrenal dysfunction in Pomeranians, was initially obtained from adrenal gland RNA by reverse transcription-polymerase chain reaction (RT-PCR), and its nucleotide sequence was determined. Genomic DNA samples from 16 Pomeranians and 30 control dogs, of seven different breeds, were tested for 21-OH gene polymorphisms by direct sequencing. No mutations affecting the primary structure and the transcriptional level of the 21-OH enzyme were found in Pomeranians. Our results indicate that the adrenal dysfunction in Pomeranians is not due to mutations of the 21-OH gene. This contrasts with the human form of CAH where 21-OH gene mutations are the major cause of the disease. (C) 2002 Elsevier Science Ltd. All rights reserved.
• 急性特発性多発性神経根炎が疑われた犬の一例

  伊藤啓, 浜本耕平, 滝口満喜, 落合謙爾 北海道獣医師会雑誌 46 (8) 292 -292 2002年08月01日 [査読無し][通常論文]
  
• 犬ヘルペスウイルス前初期遺伝子の転写動態の解析

  三好 正浩, 岡崎 克則, 滝口 満喜, 喜田 宏, 橋本 晃 The journal of veterinary medical science 64 (7) 627 -631 2002年07月25日 [査読無し][通常論文]
   

  犬ヘルペスウイルス(CHV)の前初期(IE)遺伝子は,単純ヘルペスウイルス1の感染細胞内蛋白質4(ICP4)遺伝子に相同な遺伝子で,約4.9kbのmRNAとして転写される.今回我々は,CHV IE遺伝子が感染の初期および後期には約4.8kbのmRNAとして転写される知見を得た.この4.8kbのmRNAは,後期にはIE期プロモーターからの転写が抑制されるIE期転写物のイントロン中に存在するTATAボックスの下流から転写されていた.今回の成績から,CHV IE遺伝子はCICP4遺伝子と改称することが適当であると考えられる.
• The immediate early gene of canine herpesvirus is transcribed through early and late phases

  M Miyoshi, K Okazaki, M Takiguchi, H Kida, A Hashimoto JOURNAL OF VETERINARY MEDICAL SCIENCE 64 (7) 627 -631 2002年07月 [査読無し][通常論文]
   

  The immediate early (IE) gene of canine herpesvirus (CHV), homologue of the infected cell protein 4 (ICP4) gene of herpes simplex virus 1, is transcribed as a 4.9kb mRNA during IE phase. The IE gene was further transcribed as a 4.8kb mRNA through early (E) and late (L) phases of productive infection. Transcription of the 4.8kb mRNA initiated from downstream of the TATA box in an intron which was spliced out during IE phase. The reverse transcription-polymerase chain reaction revealed that the IE promoter was turned off during L phase at a permissive temperature. We, thus, propose to redesignate the IE gene of CHV as CICP4 gene.
• Rhabdomyosarcoma (botryoid sarcoma) of the urinary bladder in a Maltese

  M Takiguchi, T Watanabe, H Okada, T Kudo, K Yamada, J Yasuda, A Hashimoto JOURNAL OF SMALL ANIMAL PRACTICE 43 (6) 269 -271 2002年06月 [査読無し][通常論文]
   

  A urinary bladder tumour was diagnosed in a two-year-old female Maltese with haematuria and pollakluria on the basis of ultrasonography and pneumocystography findings. The mass was resected, and the bladder was preserved at surgery. Histological and immunohistochemical examination confirmed the tumour to be a rhabdomyosarcoma, which has rarely been reported in small breeds of dog. There was no recurrence of the tumour at the original site in the urinary bladder two months later, when the dog died due to metastasis to the liver. This is believed to be the first report of bladder rhabdomyosarcoma in a Maltese.
• Rhabdomyosarcoma (botryoid sarcoma) of the urinary bladder in a Maltese

  M Takiguchi, T Watanabe, H Okada, T Kudo, K Yamada, J Yasuda, A Hashimoto JOURNAL OF SMALL ANIMAL PRACTICE 43 (6) 269 -271 2002年06月 [査読無し][通常論文]
   

  A urinary bladder tumour was diagnosed in a two-year-old female Maltese with haematuria and pollakluria on the basis of ultrasonography and pneumocystography findings. The mass was resected, and the bladder was preserved at surgery. Histological and immunohistochemical examination confirmed the tumour to be a rhabdomyosarcoma, which has rarely been reported in small breeds of dog. There was no recurrence of the tumour at the original site in the urinary bladder two months later, when the dog died due to metastasis to the liver. This is believed to be the first report of bladder rhabdomyosarcoma in a Maltese.
• 犬微小ウイルス(犬パルボウイルス1型)分離株の性状と血清疫学

  羽島隆之, 滝口満喜, 橋本晃, 宇根有美, 佐々木伸雄, 遠矢幸伸, 大西堂文, 前田健, CARMICHAEL L E 日本獣医学会学術集会講演要旨集 133rd 106 -106 2002年03月01日 [査読無し][通常論文]
  
• 肝皮膚症候群と診断された犬の肝臓超音波画像

  Small Animal Clinic 129: 29-31 2002年 [査読無し][通常論文]
  
• Association of canine minute virus(canine parvovirus type Ⅰ)with diseased puppies in Japan.

  J. Clin. Microbiol. 40 3993 -3998 2002年 [査読無し][通常論文]
  
• Association of canine minute virus(canine parvovirus type Ⅰ)with diseased puppies in Japan. "jointly worked"

  J. Clin. Microbiol. 40(11);3993-3998 2002年 [査読無し][通常論文]
  
• 犬のすい臓疾患におけるトリプシン様免疫活性(Trypsin‐like immunoreactivity;TLI)測定の診断的意義 II 急性すい炎の病態とTLI

  滝口満喜 動物臨床医学会年次大会プロシーディング 22nd (3) 181 -183 2001年11月16日 [査読無し][通常論文]
  
• A serological survey of minute virus of canines (MVC; Canine parvovirus type-1) in dogs in the Tokai area of Japan

  A Hashimoto, M Takiguchi, K Hirai, H Kida, LE Carmichael JAPANESE JOURNAL OF VETERINARY RESEARCH 49 (3) 249 -253 2001年11月 [査読無し][通常論文]
   

  A serological survey for antibodies to minute virus of canines (WC) by use of a hemagglutination-inhibition (HI) test was performed on sera collected from dogs in the Tokai area of Japan. Forty-one of 266 (15.4%) sera had positive titers of 1 : 40 or higher against the MVC. Results suggest that WC may have been present in dogs in Japan since, at least, 1990. From this serosurvey, WC appears to be established in the dog population in Japan. MVC may have a role as a newly recognized viral pathogen of dogs in Japan.
• A serological survey of minute virus of canines (MVC; Canine parvovirus type-1) in dogs in the Tokai area of Japan

  A Hashimoto, M Takiguchi, K Hirai, H Kida, LE Carmichael JAPANESE JOURNAL OF VETERINARY RESEARCH 49 (3) 249 -253 2001年11月 [査読無し][通常論文]
   

  A serological survey for antibodies to minute virus of canines (WC) by use of a hemagglutination-inhibition (HI) test was performed on sera collected from dogs in the Tokai area of Japan. Forty-one of 266 (15.4%) sera had positive titers of 1 : 40 or higher against the MVC. Results suggest that WC may have been present in dogs in Japan since, at least, 1990. From this serosurvey, WC appears to be established in the dog population in Japan. MVC may have a role as a newly recognized viral pathogen of dogs in Japan.
• ウシ血清アデノシンデアミナーゼ活性値と肝臓組織所見との関連性について

  安田準, 竹馬俊介, 滝口満喜, 岡田啓司, 橋本晃 獣医生化学 38 (2) 33 -37 2001年10月31日 [査読無し][通常論文]
  
• ウマヘルペスウイルス9型(EHV‐9)経鼻接種によるシリアンハムスター脳炎モデルのMRIによる経時的観察

  鈴木健吾, 浅沼武敏, 福士秀人, 平井克哉, 滝口満喜, 桑原幹典, 橋本晃 日本獣医学会学術集会講演要旨集 132nd 221 -221 2001年09月07日 [査読無し][通常論文]
  
• 非定形型副腎皮質機能低下症の犬の一例

  伊藤啓, 滝口満喜, 高田健介, 浜本耕平, 橋本晃 北海道獣医師会雑誌 45 (8) 272 -272 2001年08月01日 [査読無し][通常論文]
  
• 副腎皮質機能低下の猫の一例

  渡辺三菜子, 滝口満喜, 高田健介, 浜本耕平, 橋本晃 北海道獣医師会雑誌 45 (8) 272 -272 2001年08月01日 [査読無し][通常論文]
  
• Malignant seminoma with systemic metastases in a dog

  M Takiguchi, T Iida, T Kudo, A Hashimoto JOURNAL OF SMALL ANIMAL PRACTICE 42 (7) 360 -362 2001年07月 [査読無し][通常論文]
   

  A three-year-old male crossbred dog was presented with multiple cutaneous nodules on the dorsum. Unilateral testicular enlargement ensued. Histopathological examination of testicular tissue and the skin lesions revealed a malignant seminoma. Despite the initiation of adjuvant chemotherapy, the dog died three months later due to systemic metastases of the seminoma to the skin, scrotum, eyes, liver, kidney and peritoneum.
• Malignant seminoma with systemic metastases in a dog

  M Takiguchi, T Iida, T Kudo, A Hashimoto JOURNAL OF SMALL ANIMAL PRACTICE 42 (7) 360 -362 2001年07月 [査読無し][通常論文]
   

  A three-year-old male crossbred dog was presented with multiple cutaneous nodules on the dorsum. Unilateral testicular enlargement ensued. Histopathological examination of testicular tissue and the skin lesions revealed a malignant seminoma. Despite the initiation of adjuvant chemotherapy, the dog died three months later due to systemic metastases of the seminoma to the skin, scrotum, eyes, liver, kidney and peritoneum.
• ぼうこう・尿道疾患のX線・超音波診断

  滝口満喜, 橋本晃 獣医麻酔外科学雑誌 32 (Supplement 1) 67 -68 2001年07月01日 [査読無し][通常論文]
  
• 犬の副腎褐色細胞腫の超音波診断

  滝口満喜, 浜本耕平, 高田健介, 橋本晃 獣医麻酔外科学雑誌 32 (Supplement 1) 291 -292 2001年07月01日 [査読無し][通常論文]
  
• 自己免疫疾患の遺伝子治療

  滝口満喜 日本獣医学会学術集会講演要旨集 131st 37 -37 2001年03月05日 [査読無し][通常論文]
  
• すい管結さつマウスモデルを用いたすい臓におけるc‐metの発現動態

  浜本耕平, 滝口満喜, 橋本晃 日本獣医学会学術集会講演要旨集 131st 142 -142 2001年03月05日 [査読無し][通常論文]
  
• 犬微小ウイルス(犬パルボウイルス1型)の遺伝子の検出とウイルス分離

  望月雅美, 橋本美知留, 橋本晃, 滝口満喜, CARMICHAEL L E, PARRISH C R 日本獣医学会学術集会講演要旨集 131st 81 -81 2001年03月05日 [査読無し][通常論文]
  
• 膵管結紮マウスモデルを用いた膵臓におけるc-metの発現動態

  濱本 耕平, 滝口 満喜, 橋本 晃 日本獣医学会学術集会講演要旨集 131回 142 -142 2001年03月 [査読無し][通常論文]
  
• An improved intravesical model using human bladder cancer cell lines to optimize gene and other therapies

  T Watanabe, N Shinohara, A Sazawa, T Harabayashi, Y Ogiso, T Koyanagi, M Takiguchi, A Hashimoto, N Kuzumaki, M Yamashita, M Tanaka, HB Grossman, WF Benedict CANCER GENE THERAPY 7 (12) 1575 -1580 2000年12月 [査読無し][通常論文]
   

  Orthotopic implantation of human bladder cancer cells into immunodeficient mice is an important tool for studying the biology and effects of therapy. Nevertheless, the incidence of tumor implantation and growth by transurethral instillation of the human bladder cancer cells into murine bladders has been low or not reproducible. However, using a modified intravesical technique and the human bladder cancer cell lines, KU-7 and UM-UC-2, we have been able to obtain a high and reproducible incidence of superficial bladder tumors. Furthermore, intravesical administration of the LacZ adenovirus vector resulted in significant beta -galactosidase expression in these bladder tumors as well as the normal urothelium, which was associated with the removal of the glycosoaminoglycan layer. Because this modified technique produces a high incidence of superficial human tumor growth acid allows the efficacy of ge ne transfer to be evaluated, it should be a useful model for the study of intravesical gene therapy for human bladder cancer.
• An improved intravesical model using human bladder cancer cell lines to optimize gene and other therapies

  T Watanabe, N Shinohara, A Sazawa, T Harabayashi, Y Ogiso, T Koyanagi, M Takiguchi, A Hashimoto, N Kuzumaki, M Yamashita, M Tanaka, HB Grossman, WF Benedict CANCER GENE THERAPY 7 (12) 1575 -1580 2000年12月 [査読無し][通常論文]
   

  Orthotopic implantation of human bladder cancer cells into immunodeficient mice is an important tool for studying the biology and effects of therapy. Nevertheless, the incidence of tumor implantation and growth by transurethral instillation of the human bladder cancer cells into murine bladders has been low or not reproducible. However, using a modified intravesical technique and the human bladder cancer cell lines, KU-7 and UM-UC-2, we have been able to obtain a high and reproducible incidence of superficial bladder tumors. Furthermore, intravesical administration of the LacZ adenovirus vector resulted in significant beta -galactosidase expression in these bladder tumors as well as the normal urothelium, which was associated with the removal of the glycosoaminoglycan layer. Because this modified technique produces a high incidence of superficial human tumor growth acid allows the efficacy of ge ne transfer to be evaluated, it should be a useful model for the study of intravesical gene therapy for human bladder cancer.
• Canine extracutaneous mast-cell tumours consisting of connective tissue mast cells

  N Iwata, K Ochiai, T Kadosawa, M Takiguchi, T Umemura JOURNAL OF COMPARATIVE PATHOLOGY 123 (4) 306 -310 2000年11月 [査読無し][通常論文]
   

  (T)wo cases of canine extracutaneous mast-cell tumours were encountered, originating from the mucosa of either the oral cavity or the small intestine. The dogs had no neoplasms in the skin. Immunohistochemical and ultrastructural studies demonstrated that the neoplastic cells had the features of connective tissue mast cells. It would seem, therefore, that at least some extracutaneous forms of the neoplasm originate from connective tissue mast cells. Heparin was a useful cytological marker to diagnose this type of mast-cell tumour. (C) 2000 Harcourt Publishers Ltd.
• Canine extracutaneous mast-cell tumours consisting of connective tissue mast cells

  N Iwata, K Ochiai, T Kadosawa, M Takiguchi, T Umemura JOURNAL OF COMPARATIVE PATHOLOGY 123 (4) 306 -310 2000年11月 [査読無し][通常論文]
   

  (T)wo cases of canine extracutaneous mast-cell tumours were encountered, originating from the mucosa of either the oral cavity or the small intestine. The dogs had no neoplasms in the skin. Immunohistochemical and ultrastructural studies demonstrated that the neoplastic cells had the features of connective tissue mast cells. It would seem, therefore, that at least some extracutaneous forms of the neoplasm originate from connective tissue mast cells. Heparin was a useful cytological marker to diagnose this type of mast-cell tumour. (C) 2000 Harcourt Publishers Ltd.
• イヌの成長ホルモン反応性脱毛症における21‐ヒドロキシラーゼ遺伝子の検討

  高田健介, 北村浩, 滝口満喜, 斎藤昌之, 橋本晃 日本獣医学会学術集会講演要旨集 130th 123 2000年09月07日 [査読無し][通常論文]
  
• 新しいぼうこう癌同所性移植モデルを用いた経尿道的アデノウイルスベクター注入による遺伝子治療の有用性の検討

  渡辺孝文, 篠原信雄, 佐沢陽, 小木曾嘉文, 滝口満喜, 葛巻すすむ, 山下元幸, 田中基幹, GROSSMAN H B 日本獣医学会学術集会講演要旨集 130th 27 2000年09月07日 [査読無し][通常論文]
  
• 蛋白喪失性腸症に対する酢酸オクトレオチドによる新しい治療法の試み

  滝口満喜, 浜本耕平, 橋本晃 北海道獣医師会雑誌 44 (7) 257 -257 2000年07月01日 [査読無し][通常論文]
  
• 2‐クロロデオキシアデノシン(2‐CdA)を用いたネコ縦隔型リンパ腫に対する新しい治療法の可能性

  藤木恵, 滝口満喜, 橋本晃 北海道獣医師会雑誌 44 (7) 244 -244 2000年07月01日 [査読無し][通常論文]
  
• CTLA4IgG gene delivery prevents autoantibody production and lupus nephritis in MRL/lpr mice

  M Takiguchi, M Murakami, Nakagawa, I, A Hashimoto, T Uede FASEB JOURNAL 14 (6) A1207 -A1207 2000年04月 [査読無し][通常論文]
  
• Significance of the Grb2 and Son of sevenless (Sos) proteins in human bladder cancer cell lines

  T Watanabe, N Shinohara, K Moriya, A Sazawa, Y Kobayashi, Y Ogiso, M Takiguchi, J Yasuda, T Koyanagi, N Kuzumaki, A Hashimoto IUBMB LIFE 49 (4) 317 -320 2000年04月 [査読無し][通常論文]
   

  The epidermal growth factor (EGF) receptor has been suggested to have an important role in tumor initiation and progression of human bladder cancers. Grb2 protein, which is the downstream effector of the EGF receptor, acts as an adaptor protein between the EGF receptor and the Ras guanine-nucleotide exchange factor, son of sevenless (Sos) protein. Sos protein regulates the action of Ras protein by promoting the exchange of GDP for GTP, However, the significance of Grb2 and Sos proteins, which is related to EGF-triggered Ras activation, has not, been elucidated in human bladder cancer. The aim of the present study is to clarify the significance of these proteins in human bladder cancer cell lines. In the present study, we used four human bladder cancer cell lines (T24, KU-7, UMUC-2, UMUC-6) and two kinds of cultured normal urothelial cells (HMKU-1, HMKU-2) isolated from patients with no malignancy. We examined the expression of EGF receptor, Grb2, and Sos proteins in these cells by Western blot analysis. Furthermore, the bladder cancer cell lines were subjected to sequence analysis to identify a point mutation in the c-H-ras gene at codon 12. There was no marked difference in the expression of the EGF receptor between human bladder cancer cell lines and cultured normal urothelial cells. On the other hand, expression of Grb2 and Sos proteins was substantially increased in all human bladder cancer cell lines examined in comparison with cultured normal urothelial cells, whether codon 12 of H-ras was mutated or not. These results suggest that the amplification of both Grb2 and SOS proteins plays an important role in the carcinogenesis of human bladder cancer.
• Significance of the Grb2 and Son of sevenless (Sos) proteins in human bladder cancer cell lines

  T Watanabe, N Shinohara, K Moriya, A Sazawa, Y Kobayashi, Y Ogiso, M Takiguchi, J Yasuda, T Koyanagi, N Kuzumaki, A Hashimoto IUBMB LIFE 49 (4) 317 -320 2000年04月 [査読無し][通常論文]
   

  The epidermal growth factor (EGF) receptor has been suggested to have an important role in tumor initiation and progression of human bladder cancers. Grb2 protein, which is the downstream effector of the EGF receptor, acts as an adaptor protein between the EGF receptor and the Ras guanine-nucleotide exchange factor, son of sevenless (Sos) protein. Sos protein regulates the action of Ras protein by promoting the exchange of GDP for GTP, However, the significance of Grb2 and Sos proteins, which is related to EGF-triggered Ras activation, has not, been elucidated in human bladder cancer. The aim of the present study is to clarify the significance of these proteins in human bladder cancer cell lines. In the present study, we used four human bladder cancer cell lines (T24, KU-7, UMUC-2, UMUC-6) and two kinds of cultured normal urothelial cells (HMKU-1, HMKU-2) isolated from patients with no malignancy. We examined the expression of EGF receptor, Grb2, and Sos proteins in these cells by Western blot analysis. Furthermore, the bladder cancer cell lines were subjected to sequence analysis to identify a point mutation in the c-H-ras gene at codon 12. There was no marked difference in the expression of the EGF receptor between human bladder cancer cell lines and cultured normal urothelial cells. On the other hand, expression of Grb2 and Sos proteins was substantially increased in all human bladder cancer cell lines examined in comparison with cultured normal urothelial cells, whether codon 12 of H-ras was mutated or not. These results suggest that the amplification of both Grb2 and SOS proteins plays an important role in the carcinogenesis of human bladder cancer.
• ぼうこう内腫りゅう性病変の画像所見を示したぼうこう血腫の1例

  渡辺孝文, 滝口満喜, 工藤忠明, 橋本晃 北海道獣医師会雑誌 44 (4) 104 -106 2000年04月01日 [査読無し][通常論文]
  
• イヌヘルペスウイルス(CHV)感染新生子犬の脳病変におけるウイルス抗原及びウイルスゲノムの分布

  西野 亜紀, 滝口 満喜, 橋本 晃, 岡崎 克則, 喜田 宏 日本獣医学会学術集会講演要旨集 129回 47 -47 2000年03月 [査読無し][通常論文]
  
• CTLA4IgG gene delivery prevents autoantibody production and lupus nephritis in MRL/lpr mice

  M Takiguchi, M Murakami, Nakagawa, I, Saito, I, A Hashimoto, T Uede LIFE SCIENCES 66 (11) 991 -1001 2000年02月 [査読無し][通常論文]
   

  MRL/MP-lpr/lpr (MRL/lpr) mice spontaneously develop an autoimmune syndrome closely resembling systemic lupus erythematosus (SLE) in humans, characterized by hypergammaglobulinemia, various autoantibody production, and the development of fatal glomerulonephritis. We have previously demonstrated that systemic administration of soluble form of CTLA4IgG prevented autoantibody-related diseases in MRL/lpr mice. To test the potential protective effects of CTLA4IgG gene delivery on the development of lupus nephritis, we injected MRL/lpr mice with, a recombinant adenovirus vector containing CTLA4IgG gene, Adex1CACTLA4IgG (AdCTLA4IgG). It was demonstrated that a single administration of intravenous injection of AdCTLA4IgG into MRL/lpr mice resulted in almost complete amelioration of lupus nephritis.
• Suppressive effects of dominant negative ras mutant N116Y on transformed phenotypes of human bladder cancer cells

  T Watanabe, N Shinohara, A Sazawa, Y Kobayashi, Y Ogiso, T Kimura, M Takiguchi, J Yasuda, A Hashimoto, T Koyanagi, N Kuzumaki CANCER LETTERS 149 (1-2) 195 -202 2000年02月 [査読無し][通常論文]
   

  To investigate the suppressive effect of dominant negative H-ras mutant N116Y on transformed phenotypes, we established two N116Y ras mutant stable transfectant clones (C5, C13) of human bladder cancer cell line, UMUC-2. These N116Y ras mutant transfectants, especially the C5 cells, showed a dramatic change of cellular morphology and significantly reduced growth in soft agar compared to their control. Furthermore, phosphorylation of the Jun NH2-terminal kinase (JNK) was significantly decreased in these transfectants compared to the control. These results suggest that the N116Y-induced suppression of transformed phenotypes in UMUC-2 cells is associated with inhibition of JNK phosphorylation, (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.
• CTLA4IgG gene delivery prevents autoantibody production and lupus nephritis in MRL/lpr mice

  M Takiguchi, M Murakami, Nakagawa, I, Saito, I, A Hashimoto, T Uede LIFE SCIENCES 66 (11) 991 -1001 2000年02月 [査読無し][通常論文]
   

  MRL/MP-lpr/lpr (MRL/lpr) mice spontaneously develop an autoimmune syndrome closely resembling systemic lupus erythematosus (SLE) in humans, characterized by hypergammaglobulinemia, various autoantibody production, and the development of fatal glomerulonephritis. We have previously demonstrated that systemic administration of soluble form of CTLA4IgG prevented autoantibody-related diseases in MRL/lpr mice. To test the potential protective effects of CTLA4IgG gene delivery on the development of lupus nephritis, we injected MRL/lpr mice with, a recombinant adenovirus vector containing CTLA4IgG gene, Adex1CACTLA4IgG (AdCTLA4IgG). It was demonstrated that a single administration of intravenous injection of AdCTLA4IgG into MRL/lpr mice resulted in almost complete amelioration of lupus nephritis.
• Suppressive effects of dominant negative ras mutant N116Y on transformed phenotypes of human bladder cancer cells

  T Watanabe, N Shinohara, A Sazawa, Y Kobayashi, Y Ogiso, T Kimura, M Takiguchi, J Yasuda, A Hashimoto, T Koyanagi, N Kuzumaki CANCER LETTERS 149 (1-2) 195 -202 2000年02月 [査読無し][通常論文]
   

  To investigate the suppressive effect of dominant negative H-ras mutant N116Y on transformed phenotypes, we established two N116Y ras mutant stable transfectant clones (C5, C13) of human bladder cancer cell line, UMUC-2. These N116Y ras mutant transfectants, especially the C5 cells, showed a dramatic change of cellular morphology and significantly reduced growth in soft agar compared to their control. Furthermore, phosphorylation of the Jun NH2-terminal kinase (JNK) was significantly decreased in these transfectants compared to the control. These results suggest that the N116Y-induced suppression of transformed phenotypes in UMUC-2 cells is associated with inhibition of JNK phosphorylation, (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.
• 膀胱内腫瘤性病変の画像所見を示した膀胱血腫の1例(共著)

  渡邉 孝文, 滝口 満喜, 工藤 忠明, 橋本 晃 北海道獣医師会雑誌 44 (4) 104 -106 2000年 [査読無し][通常論文]
  
• Involvement of CD28/CTLA4-B7 costimulatory pathway in the development of lymphadenopathy and splenomegaly in MRL/lpr mice

  M Takiguchi, M Murakami, Nakagawa, I, MM Rashid, N Tosa, S Chikuma, A Hashimoto, T Uede JOURNAL OF VETERINARY MEDICAL SCIENCE 62 (1) 29 -36 2000年01月 [査読無し][通常論文]
   

  MRL/lpr mouse is an established animal model which develops autoimmune diseases including glomerulonephritis, sialoadenitis, hepatitis and inflammatory lung disease. Additionally, it has been reported that lpr strains uniquely accumulate CD3(+)CD4(-)CD8(-)B220(+) (double negative, DN) T cells in lymphoid organs leading to lymphadenopathy and splenomegaly. To investigate the role of CD28/CTLA4-B7 pathway in the development of lymphadenopathy and splenomegaly, MRL/lpr mice were treated with soluble form of CTLA4 molecules. CTLA4IgG, which efficiently blocks this pathway. It was demonstrated that (i) the development of DN T cells was independent of the CD28/CTLA4-B7 pathway, (ii) the CD28/CTLA4-B7 pathway was required for the development of lymphadenopathy and splenomegaly, (iii) the CD28/CTLA4-B7 pathway was important for the accumulation of various cell populations in the lymph node and spleen, (iv) composition of the accumulating cell populations was not altered by CTLA4IgG treatment, and (v) activation of conventional T cells and IL-4 production from conventional T cells were the CD28/CTLA4-B7 pathway dependent. Thus, we concluded that the CD28/CTLA4-B7 pathway was required for the development of full-blown lymphadenopathy and splenomegaly in MRL/lpr mice.
• Structure of the infected cell protein 0 gene of canine herpesvirus

  M Miyoshi, M Takiguchi, J Yasuda, A Hashimoto, A Takada, K Okazaki, H Kida ARCHIVES OF VIROLOGY 145 (8) 1715 -1723 2000年 [査読無し][通常論文]
   

  The canine herpesvirus infected cell protein 0 (CICP0) gene was sequenced. The CICP0 gene was transcribed as a 1.4 kb mRNA from the end of the unique long region nearby the internal repeat during early phase of productive infection of the virus. An open reading frame of the gene encodes a polypeptide of 333 amino acids. The RING finger domain and acidic transcriptional activation domain were found at the N-terminus and within the middle region in the deduced amino acid sequence, respectively, suggesting that the CICP0, like the ICP0 of herpes simplex virus 1, is a transactivating protein.
• Involvement of CD28/CTLA4-B7 costimulatory pathway in the development of lymphadenopathy and splenomegaly in MRL/lpr mice

  M Takiguchi, M Murakami, Nakagawa, I, MM Rashid, N Tosa, S Chikuma, A Hashimoto, T Uede JOURNAL OF VETERINARY MEDICAL SCIENCE 62 (1) 29 -36 2000年01月 [査読無し][通常論文]
   

  MRL/lpr mouse is an established animal model which develops autoimmune diseases including glomerulonephritis, sialoadenitis, hepatitis and inflammatory lung disease. Additionally, it has been reported that lpr strains uniquely accumulate CD3(+)CD4(-)CD8(-)B220(+) (double negative, DN) T cells in lymphoid organs leading to lymphadenopathy and splenomegaly. To investigate the role of CD28/CTLA4-B7 pathway in the development of lymphadenopathy and splenomegaly, MRL/lpr mice were treated with soluble form of CTLA4 molecules. CTLA4IgG, which efficiently blocks this pathway. It was demonstrated that (i) the development of DN T cells was independent of the CD28/CTLA4-B7 pathway, (ii) the CD28/CTLA4-B7 pathway was required for the development of lymphadenopathy and splenomegaly, (iii) the CD28/CTLA4-B7 pathway was important for the accumulation of various cell populations in the lymph node and spleen, (iv) composition of the accumulating cell populations was not altered by CTLA4IgG treatment, and (v) activation of conventional T cells and IL-4 production from conventional T cells were the CD28/CTLA4-B7 pathway dependent. Thus, we concluded that the CD28/CTLA4-B7 pathway was required for the development of full-blown lymphadenopathy and splenomegaly in MRL/lpr mice.
• Structure of the infected cell protein O gene of canine herpesvirus. "jointly worked"

  Arch. Virol. 145 (8) 1715 -1723 2000年 [査読無し][通常論文]
  
• 犬の皮膚病に対する動物用超音波洗浄装置の応用

  安田準, 中尾喜一, 清水恭子, 釜田悟, 北村之利, 滝口満喜 獣医畜産新報 52 (939) 801 -804 1999年10月01日 [査読無し][通常論文]
  
• Dominant negative ras mutant N116Y発現アデノウイルスベクターを用いたぼうこう癌に対する遺伝子治療の基礎的研究

  渡辺孝文, 篠原信雄, 佐沢陽, 滝口満喜, 小柳知彦, 葛巻すすむ, 橋本晃 日本獣医学会学術集会講演要旨集 128th 186 -186 1999年09月01日 [査読無し][通常論文]
  
• 脳包虫症ラットモデルのMRI画像観察

  松本夕佳利, 浅沼武敏, 中尾稔, 中谷和宏, 滝口満喜, 伊藤亮, 桑原幹典, 橋本晃 日本獣医学会学術集会講演要旨集 128th 167 -167 1999年09月01日 [査読無し][通常論文]
  
• CTLA4IgG発現アデノウイルスベクターを用いたループス腎炎への遺伝子治療の試み

  滝口満喜, 村上正晃, 中川泉, 斉藤泉, 橋本晃, 上出利光 日本獣医学会学術集会講演要旨集 128th 20 -20 1999年09月01日 [査読無し][通常論文]
  
• 犬副腎髄質褐色細胞腫の画像診断と尿中カテコールアミン代謝産物の診断的意義

  滝口 満喜, 宮田 佳代子, 橋本 晃 北海道獣医師会雑誌 43 (8) 256 -256 1999年08月
• インスリン療法により重度の溶血性貧血を呈した糖尿病性ケトアシドーシスの猫の1例

  濱本 耕平, 滝口 満喜, 橋本 晃 北海道獣医師会雑誌 43 (8) 253 -253 1999年08月
• Combination of CTLA41GG and FTY720 suppresses development of obliterative bronchiolitis and respiratory epithelial injury in a murine heterotopic airway model

  K Konishi, M Murakami, A Yamada, M Takiguchi, M Morikawa, T Omura, S Todo, T Uede TRANSPLANTATION 67 (9) S605 -S605 1999年05月 [査読無し][通常論文]
  
• Detection of canine herpesvirus DNA in the ganglionic neurons and the lymph node lymphocytes of latently infected dogs

  M Miyoshi, Y Ishii, M Takiguchi, A Takada, J Yasuda, A Hashimoto, K Okazaki, H Kida JOURNAL OF VETERINARY MEDICAL SCIENCE 61 (4) 375 -379 1999年04月 [査読無し][通常論文]
   

  TO determine the site of latent infection of canine herpesvirus (CHV), tissues from dogs convalescent from acute infection with CHV were examined for the presence of viral genome DNA by the nested polymerase chain reaction. CHV DNA was detected in the trigeminal ganglia and the retropharyngeal lymph nodes. In situ hybridization study of the tissues revealed that CHV genome persisted in the nuclei of ganglionic neurons and lymphocytes.
• Blockade of CD28/CTLA4-B7 pathway prevented autoantibody-related diseases but not lung disease in MRL/lpr mice

  M Takiguchi, M Murakami, Nakagawa, I, A Yamada, S Chikuma, Y Kawaguchi, A Hashimoto, T Uede LABORATORY INVESTIGATION 79 (3) 317 -326 1999年03月 [査読無し][通常論文]
   

  We studied the role of CD28/CTLA4 costimulatory T-cell activation pathway on the pathogenesis of MRL/Ipr mice. Administration of CTLA4IgG from day 0 significantly inhibited autoantibody production such as anti-double-stranded DNA antibody and rheumatoid factor. In addition, end-organ diseases in kidney, salivary gland, and liver were significantly improved. Improvement of pathologic findings coincided with a significant improvement in survival. At 350 days of age, 90% of mice treated with CTLA4IgG from day 0 were still alive, compared with none of mice treated with hIgG. As expected, activation of conventional T cells was significantly inhibited after CTLA4IgG treatment. However, lung disease that was characterized by perivascular accumulation and interstitial infiltration of lymphocytes and macrophages was not inhibited. Even after CTLA4IgG treatment from day 0, pathologic findings of lung disease were not improved. Additionally, the expression of activation markers such as B7-1, B7-2, CD71, ICAM1, and LFA1 on Mac1(+) fraction in both spleen and lung and the concentration of TNF alpha in bronchoalveolar lavage fluid were not significantly suppressed. These results demonstrated that lung disease was independent of the CD28/CTLA4-B7 pathway. Thus, this study emphasizes the differential dependence of the CD28/CTLA4-B7 pathway in development of diseases in MRL/Ipr mice.
• Blockade of CD28/CTLA4-B7 pathway prevented autoantibody-related diseases but not lung disease in MRL/lpr mice

  M Takiguchi, M Murakami, Nakagawa, I, A Yamada, S Chikuma, Y Kawaguchi, A Hashimoto, T Uede LABORATORY INVESTIGATION 79 (3) 317 -326 1999年03月 [査読無し][通常論文]
   

  We studied the role of CD28/CTLA4 costimulatory T-cell activation pathway on the pathogenesis of MRL/Ipr mice. Administration of CTLA4IgG from day 0 significantly inhibited autoantibody production such as anti-double-stranded DNA antibody and rheumatoid factor. In addition, end-organ diseases in kidney, salivary gland, and liver were significantly improved. Improvement of pathologic findings coincided with a significant improvement in survival. At 350 days of age, 90% of mice treated with CTLA4IgG from day 0 were still alive, compared with none of mice treated with hIgG. As expected, activation of conventional T cells was significantly inhibited after CTLA4IgG treatment. However, lung disease that was characterized by perivascular accumulation and interstitial infiltration of lymphocytes and macrophages was not inhibited. Even after CTLA4IgG treatment from day 0, pathologic findings of lung disease were not improved. Additionally, the expression of activation markers such as B7-1, B7-2, CD71, ICAM1, and LFA1 on Mac1(+) fraction in both spleen and lung and the concentration of TNF alpha in bronchoalveolar lavage fluid were not significantly suppressed. These results demonstrated that lung disease was independent of the CD28/CTLA4-B7 pathway. Thus, this study emphasizes the differential dependence of the CD28/CTLA4-B7 pathway in development of diseases in MRL/Ipr mice.
• MRL/lprマウス肺病変形成におけるCD28/CTLA4‐B7補助シグナルの役割

  滝口満喜, 村上正晃, 中川泉, 安田準, 橋本晃, 上出利光 日本獣医学会学術集会講演要旨集 127th 68 -68 1999年03月01日 [査読無し][通常論文]
  
• 動物用超音波洗浄装置を用いた犬の慢性皮膚疾患の治療について

  中尾喜一, 安田準, 清水恭子, 北村之利, 滝口満喜, 橋本晃 日本産業動物獣医学会・日本小動物獣医学会・日本獣医公衆衛生学会年次大会 1998 362 1999年02月 [査読無し][通常論文]
  
• X線および超音波検査で副腎髄質腫ようが疑われた犬の一例

  宮田佳代子, 滝口満喜, 安田準, 橋本晃 日本産業動物獣医学会・日本小動物獣医学会・日本獣医公衆衛生学会年次大会 1998 354 1999年02月 [査読無し][通常論文]
  
• 犬の皮膚病に対する動物用超音波洗浄装置の応用(共著)

  安田 準, 中尾 喜一, 清水 恭子, 釜田 悟, 北村 之利, 滝口 満喜 獣医畜産新報 52 (10) 801 -804 1999年 [査読無し][通常論文]
  
• Structure of the immediate early gene of canine herpesvirus - Brief report

  M Miyoshi, M Takiguchi, J Yasuda, A Hashimoto, A Takada, K Okazaki, H Kida ARCHIVES OF VIROLOGY 144 (2) 407 -420 1999年 [査読無し][通常論文]
   

  The nucleotide sequence of the immediate early (IE) gene of canine herpesvirus was determined. This gene was located in the inverted repeat regions, encoding a polypeptide of 1,383 amino acids. The predicted amino acid sequence was most closely related to that of the feline herpesvirus 1 IE protein among those of other alphaherpesviruses. DNA binding and transcriptional activation domains were found in the IE protein. A spliced region of the IE gene transcript was determined in its 5' non-coding region.
• Preliminary study on clinical application of endoscopic ultrasonography (EUS) in small animal practice: EUS findings of experimentally-induced cystic lesion in the gastric wall in dogs (in Japanese with English Summary) 'jointly worked'

  Jpn. J. Vet. Imag 10 37 -40 1999年 [査読無し][通常論文]
  
• Structure of immediate early gene of canine herpesvirus. "jointly worked"

  Arch. Virol. 144 (2) 407 -420 1999年 [査読無し][通常論文]
  
• Detection of canine herpesvirns DNA in the ganglionic neurons and the lymph node lymphocytes of latently infected dogs. "jointly worked"

  Masahiro Miyoshi, Yuki Ishii, Mitsuyoshi Takiguchi, Ayato Takada, Jun Yasuda, Akira Hashimoto, Katsunori Okazaki, Hiroshi Kida J. Ved. Med. Sci. 61 (4) 375 -379 1999年 [査読無し][通常論文]
  
• Preliminary study on clinical application of endoscopic ultrasonography (EUS) in small animal practice: EUS findings of experimentally-induced cystic lesion in the gastric wall in dogs (in Japanese with English Summary) 'jointly worked'

  Jpn. J. Vet. Imag 10 37 -40 1999年 [査読無し][通常論文]
  
• Laboratory of Pathobiology

  HASHIMOTO Akira, TAKIGUCHI Mitsuyoshi Japanese journal of veterinary research 46 (2) 90 -91 1998年11月30日
• Endoscopic ultrasonography of the pancreas in the dog

  Y Morita, M Takiguchi, J Yasuda, T Kitamura, M Syakalima, KD Eom, A Hashimoto VETERINARY RADIOLOGY & ULTRASOUND 39 (6) 552 -556 1998年11月 [査読無し][通常論文]
   

  Endoscopic ultrasonography was done in 12 normal adult dogs to investigate its efficacy in visualization of the pancreas. The endoscopic ultrasonographic device used in the present study had a curved-array ultrasound transducer mounted in front of the objective lens. The tip of the ultrasonic endoscope was inserted into the stomach, and all examinations of the pancreas were performed from within the stomach. Endoscopic ultrasoraography provided good images of most parts of the pancreas except for the ends of each lobe, Useful information about the pancreatic parenchyma, including pancreatic lobular structure, pancreatic duct, and vessels of the pancreas was obtained by endoscopic ultrasonography, Blood flow within vessels was detected using color Doppler and pulsed-wave Doppler examination.. These results suggest that endoscopic ultrasonography is available as an effective diagnostic modality in small animal practice.
• Endoscopic ultrasonography of the pancreas in the dog

  Y Morita, M Takiguchi, J Yasuda, T Kitamura, M Syakalima, KD Eom, A Hashimoto VETERINARY RADIOLOGY & ULTRASOUND 39 (6) 552 -556 1998年11月 [査読無し][通常論文]
   

  Endoscopic ultrasonography was done in 12 normal adult dogs to investigate its efficacy in visualization of the pancreas. The endoscopic ultrasonographic device used in the present study had a curved-array ultrasound transducer mounted in front of the objective lens. The tip of the ultrasonic endoscope was inserted into the stomach, and all examinations of the pancreas were performed from within the stomach. Endoscopic ultrasoraography provided good images of most parts of the pancreas except for the ends of each lobe, Useful information about the pancreatic parenchyma, including pancreatic lobular structure, pancreatic duct, and vessels of the pancreas was obtained by endoscopic ultrasonography, Blood flow within vessels was detected using color Doppler and pulsed-wave Doppler examination.. These results suggest that endoscopic ultrasonography is available as an effective diagnostic modality in small animal practice.
• Endoscopic ultrasonography of the pancreas in the dog

  Y Morita, M Takiguchi, J Yasuda, T Kitamura, M Syakalima, KD Eom, A Hashimoto VETERINARY RADIOLOGY & ULTRASOUND 39 (6) 552 -556 1998年11月 [査読無し][通常論文]
   

  Endoscopic ultrasonography was done in 12 normal adult dogs to investigate its efficacy in visualization of the pancreas. The endoscopic ultrasonographic device used in the present study had a curved-array ultrasound transducer mounted in front of the objective lens. The tip of the ultrasonic endoscope was inserted into the stomach, and all examinations of the pancreas were performed from within the stomach. Endoscopic ultrasoraography provided good images of most parts of the pancreas except for the ends of each lobe, Useful information about the pancreatic parenchyma, including pancreatic lobular structure, pancreatic duct, and vessels of the pancreas was obtained by endoscopic ultrasonography, Blood flow within vessels was detected using color Doppler and pulsed-wave Doppler examination.. These results suggest that endoscopic ultrasonography is available as an effective diagnostic modality in small animal practice.
• Endoscopic ultrasonographic findings of the pancreas after pancreatic duct ligation in the dog

  Y Morita, M Takiguchi, J Yasuda, KD Eom, A Hashimoto VETERINARY RADIOLOGY & ULTRASOUND 39 (6) 557 -562 1998年11月 [査読無し][通常論文]
   

  Endoscopic ultrasonographic evaluation and gray-scale histogram analysis of pancreatic atrophy after pancreatic duct ligation were performed in four normal adult dogs. Using endoscopic ultrasonography, markedly dilated pancreatic ducts were visualized, and the pancreas became gradually atrophied with a hyperechoic parenchyma, In gray-scale histogram analysis of the pancreas, mean brightness increased gradually until 8 weeks, then decreased temporally. Standard deviation of the histogram increased markedly and then fluctuated until the 4th week, after which the mean brightness and standard deviation became stable. At 4 weeks postoperatively, collapse of most pancreatic acinar structures were observed, and each atrophic lobule was associated with a significantly large amount of interstitial fibrous tissue at histopathology, At 12 weeks postoperatively, most exocrine tissue had decreased and was partly replaced by fibrous and fatty tissue, These changes of mean brightness and standard deviation reflected the histologic analysis. These findings indicated that endoscopic ultrasonography is a useful technique to image such atrophic disorders of the pancreas as chronic pancreatitis. Furthermore, gray-scale histogram analysis provides helpful information for ultrasonographic tissue characterization of the pancreas.
• 1prマウス肺病変形成におけるCD28/CTLA4-B7補助シグナルの役割

  滝口 満喜, 村上 正晃, 中川 泉, 橋本 晃, 上出 利光 日本臨床免疫学会会誌 (26回抄録集) 376 -376 1998年10月
• lprマウス肺病変形成におけるCD28/CTLA4‐B7補助シグナルの役割

  滝口満喜, 村上正晃, 中川泉, 橋本晃, 上出利光 日本免疫学会総会・学術集会記録 28 376 1998年10月 [査読無し][通常論文]
  
• 小動物臨床におけるアイソザイム診断法

  安田準, 滝口満喜, 橋本晃, SYAKALIMA M S 動物臨床医学 7 (2) 57 -65 1998年09月 [査読無し][通常論文]
  
• 犬の血中アデノシンデアミナーゼ活性の臨床的意義について

  安田 準, 高橋 恵理子, 滝口 満喜, 橋本 晃 北海道獣医師会雑誌 42 (8) 290 -290 1998年08月
• 犬のすい臓腺房性萎縮症の病理組織学的知見補遺

  東陽子, 滝口満喜, 安田準, 落合謙爾, 工藤忠明, 岩永敏彦, 橋本晃 日本獣医学会学術集会講演要旨集 126th 263 -263 1998年08月 [査読無し][通常論文]
  
• MRL/lprマウスの病態発生におけるCD28/CTLA4‐B7補助シグナルの関わり

  滝口満喜, 村上正晃, 中川泉, 安田準, 橋本晃, 上出利光 日本獣医学会学術集会講演要旨集 126th 22 -22 1998年08月 [査読無し][通常論文]
  
• Endoscopic and transcutaneous ultrasonographic findings and grey-scale histogram analysis in dogs with caerulein-induced pancreatitis

  Y Morita, M Takiguchi, J Yasuda, T Kitamura, M Syakalima, A Hashimoto VETERINARY QUARTERLY 20 (3) 89 -92 1998年07月 [査読無し][通常論文]
   

  Endoscopic ultrasonography (EUS), grey-scale histogram analysis of EUS images, and transcutaneous ultrasonography (TUS) were done in four dogs with caerulein-induced pancreatitis. One other dog was subjected to laparotomy and biopsy specimens were collected for histopathology, By EUS, the pancreatic lesions were first detected at 60 minutes after the start of caerulein infusion. They were detected after 120 to 150 minutes when using TUS, EUS findings included swelling, a more distinct lobular pattern, subcapsular hypoechoic areas, and anechoic stripes through the pancreatic tissue. No marked changes in the histogram analysis was seen until 30 minutes. From 30 to 60 minutes, a decrease in the mean brightness of the pancreatic tissue was observed. These changes in mean brightness reflected histopathological findings showing vacuolization of acinar cells and interstitial oedema of the pancreas. These findings indicated that EUS can detect slight and diffuse changes in pancreatic tissue. Furthermore, grey-scale histogram analysis detects histopathological changes more sensitively than endoscopic ultrasound images.
• Endoscopic and transcutaneous ultrasonographic findings and grey-scale histogram analysis in dogs with caerulein-induced pancreatitis

  Y Morita, M Takiguchi, J Yasuda, T Kitamura, M Syakalima, A Hashimoto VETERINARY QUARTERLY 20 (3) 89 -92 1998年07月 [査読無し][通常論文]
   

  Endoscopic ultrasonography (EUS), grey-scale histogram analysis of EUS images, and transcutaneous ultrasonography (TUS) were done in four dogs with caerulein-induced pancreatitis. One other dog was subjected to laparotomy and biopsy specimens were collected for histopathology, By EUS, the pancreatic lesions were first detected at 60 minutes after the start of caerulein infusion. They were detected after 120 to 150 minutes when using TUS, EUS findings included swelling, a more distinct lobular pattern, subcapsular hypoechoic areas, and anechoic stripes through the pancreatic tissue. No marked changes in the histogram analysis was seen until 30 minutes. From 30 to 60 minutes, a decrease in the mean brightness of the pancreatic tissue was observed. These changes in mean brightness reflected histopathological findings showing vacuolization of acinar cells and interstitial oedema of the pancreas. These findings indicated that EUS can detect slight and diffuse changes in pancreatic tissue. Furthermore, grey-scale histogram analysis detects histopathological changes more sensitively than endoscopic ultrasound images.
• 超音波内視鏡検査(EUS)の小動物臨床への応用に関する研究 イヌの実験的胃壁嚢胞性病変のEUS画像(予報)

  森田豊, 滝口満喜, 安田準, 橋本晃 獣医画像診断 (10) 37 -40 1998年06月 [査読無し][通常論文]
  
• The canine alkaline phosphatases: A review of the isoenzymes in serum, analytical methods and their diagnostic application

  M Syakalima, M Takiguchi, J Yasuda, A Hashimoto JAPANESE JOURNAL OF VETERINARY RESEARCH 46 (1) 3 -11 1998年05月 [査読無し][通常論文]
   

  This paper reviews the alkaline phosphatases in canine serum, the analytical methods used for qualitative and/or quantitative detection of these isoenzymes, and the diagnostic significancy of each of these isoenzymes. The paper further describes some of the latest advances in our knowledge of the canine alkaline phosphatases and possible areas of future research.
• The canine alkaline phosphatases: A review of the isoenzymes in serum, analytical methods and their diagnostic application

  M Syakalima, M Takiguchi, J Yasuda, A Hashimoto JAPANESE JOURNAL OF VETERINARY RESEARCH 46 (1) 3 -11 1998年05月 [査読無し][通常論文]
   

  This paper reviews the alkaline phosphatases in canine serum, the analytical methods used for qualitative and/or quantitative detection of these isoenzymes, and the diagnostic significancy of each of these isoenzymes. The paper further describes some of the latest advances in our knowledge of the canine alkaline phosphatases and possible areas of future research.
• Blockade of CD28/CTLA4 pathway prevented almost diseases and lymphadenopathy but not lung disease in MRL/lpr mice.

  M Takiguchi, M Murakami, Nakagawa, I, A Yamada, S Chikuma, T Uede FASEB JOURNAL 12 (5) A1093 -A1093 1998年03月 [査読無し][通常論文]
  
• Ultrasonographic and serologic studies of experimental cysticercosis in rats infected with Taenia taeniaeformis

  A Ito, Y Sakakibara, L Ma, K Asano, M Takiguchi, J Yasuda, A Hashimoto PARASITE IMMUNOLOGY 20 (3) 105 -110 1998年03月 [査読無し][通常論文]
   

  Rats experimentally infected with Taenia taeniaeformis were followed-lip until 14 weeks post inoculation with eggs (PIE) by hepatic ultrasonographic (US) image and serum antibody response analyses. Parasitic cysts could be imaged as small (2 mm in diameter) anechoic areas with or without a parenthesis-like echogenic small line from two weeks PIE. Immunoblot analysis using antigens from oncospheres (TtO), 30-day-old (TtM-30) and 300-day-old metacestodes (TtM-300) revealed that: (1) these three different developmental stages showed their own unique patterns suggesting the presence of stage-specific antigens; (2) faint IgM antibody responses to some components of TtO and TtM-30 or TtM-300 could be detected from one and two weeks PIE, respectively, and (3) IgG responses to some major components of both TtO and TtM-300, and TtM-30 were easily detected from four and five weeks PIE onwards, respectively. Both TtO and TtM (especially TtM-300) appeared to be highly useful for detection of antibody responses in experimentally infected mts. Due to the easiness in preparation of antigens, fully developed metacestodes may be the best candidate antigens for serodiagnosis. These results strongly suggest that both US image and antibody analyses using antigens from fully developed metacestodes are useful for detection of the early stage of cysticercosis in laboratory animal model.
• Ultrasonographic and serologic studies of experimental cysticercosis in rats infected with Taenia taeniaeformis

  A Ito, Y Sakakibara, L Ma, K Asano, M Takiguchi, J Yasuda, A Hashimoto PARASITE IMMUNOLOGY 20 (3) 105 -110 1998年03月 [査読無し][通常論文]
   

  Rats experimentally infected with Taenia taeniaeformis were followed-lip until 14 weeks post inoculation with eggs (PIE) by hepatic ultrasonographic (US) image and serum antibody response analyses. Parasitic cysts could be imaged as small (2 mm in diameter) anechoic areas with or without a parenthesis-like echogenic small line from two weeks PIE. Immunoblot analysis using antigens from oncospheres (TtO), 30-day-old (TtM-30) and 300-day-old metacestodes (TtM-300) revealed that: (1) these three different developmental stages showed their own unique patterns suggesting the presence of stage-specific antigens; (2) faint IgM antibody responses to some components of TtO and TtM-30 or TtM-300 could be detected from one and two weeks PIE, respectively, and (3) IgG responses to some major components of both TtO and TtM-300, and TtM-30 were easily detected from four and five weeks PIE onwards, respectively. Both TtO and TtM (especially TtM-300) appeared to be highly useful for detection of antibody responses in experimentally infected mts. Due to the easiness in preparation of antigens, fully developed metacestodes may be the best candidate antigens for serodiagnosis. These results strongly suggest that both US image and antibody analyses using antigens from fully developed metacestodes are useful for detection of the early stage of cysticercosis in laboratory animal model.
• イヌヘルペスウイルスの潜伏感染部位の同定

  三好 正浩, 石井 由紀, 滝口 満喜, 安田 準, 橋本 晃, 高田 礼人, 岡崎 克則, 喜田 宏 日本獣医学会学術集会講演要旨集 125回 140 -140 1998年03月 [査読無し][通常論文]
  
• イヌのアルカリフォスファターゼアイソザイムの定量分析の試み

  SYAKALIMA M, 安田準, 滝口満喜, 橋本晃 日本獣医学会学術集会講演要旨集 125th 271 -271 1998年03月 [査読無し][通常論文]
  
• 犬のすい外分泌不全症への血清トリプシン様免疫活性(TLI)測定の応用

  森田豊, 滝口満喜, 安田準, 橋本晃 日本産業動物獣医学会・日本小動物獣医学会・日本獣医公衆衛生学会年次大会 1997 292 -293 1998年02月 [査読無し][通常論文]
  
• 超音波内視鏡検査(EUS)の小動物臨床への応用に関する研究－イヌの実験的胃壁嚢胞性病変のEUS画像(予報)（共著）

  獣医画像診断 10: 37-40 1998年 [査読無し][通常論文]
  
• 小動物臨床におけるアイソザイムの診断（共著）

  動物臨床医学 7: 57-65 1998年 [査読無し][通常論文]
  
• Comparison of attenuation and liver-kidney contrast of liver ultrasonographs with histology and biochemistry in dogs with experimentally induced steroid hepatopathy

  M Syakalima, M Takiguchi, J Yasuda, Y Morita, A Hashimoto VETERINARY QUARTERLY 20 (1) 18 -22 1998年01月 [査読無し][通常論文]
   

  Digital analysis of liver ultrasound images (USGs) was compared to histological and serum enzyme activity results in dogs with steroid-induced hepatopathy. Steroid hepatopathy was used as a model for diffuse liver diseases. Prednisolone administration resulted in increased acoustic backscatter (hyperechogenicity) of the liver,vith reference to the kidney and significant depth attenuation (hyper-attenuation). Absolute changes were determined by histogram analysis of echo means (Ems) of area samples (1x1cm) of liver and kidney at the depth of 2 cm (liver-kidney contrast) and at 2 ems and 4 cm (depth attenuation). Liver-kidney contrast histograms correlated well with histology but were more sensitive than serum enzyme activity and subjective visual interpretation. Depth attenuation was the earliest detectable acoustic change. These results suggested that depth attenuation is an early and sensitive indicator of steroid hepatopathy. Liver-kidney contrast correlates well with histology and may complement biopsy examination during follow-up studies.
• Comparison of attenuation and liver-kidney contrast of liver ultrasonographs with histology and biochemistry in dogs with experimentally induced steroid hepatopathy

  M Syakalima, M Takiguchi, J Yasuda, Y Morita, A Hashimoto VETERINARY QUARTERLY 20 (1) 18 -22 1998年01月 [査読無し][通常論文]
   

  Digital analysis of liver ultrasound images (USGs) was compared to histological and serum enzyme activity results in dogs with steroid-induced hepatopathy. Steroid hepatopathy was used as a model for diffuse liver diseases. Prednisolone administration resulted in increased acoustic backscatter (hyperechogenicity) of the liver,vith reference to the kidney and significant depth attenuation (hyper-attenuation). Absolute changes were determined by histogram analysis of echo means (Ems) of area samples (1x1cm) of liver and kidney at the depth of 2 cm (liver-kidney contrast) and at 2 ems and 4 cm (depth attenuation). Liver-kidney contrast histograms correlated well with histology but were more sensitive than serum enzyme activity and subjective visual interpretation. Depth attenuation was the earliest detectable acoustic change. These results suggested that depth attenuation is an early and sensitive indicator of steroid hepatopathy. Liver-kidney contrast correlates well with histology and may complement biopsy examination during follow-up studies.
• Separation and quantification of corticosteroid-induced, bone and liver alkaline phosphatase isoenzymes in canine serum

  M Syakalima, M Takiguchi, J Yasuda, A Hashimoto JOURNAL OF VETERINARY MEDICINE SERIES A-PHYSIOLOGY PATHOLOGY CLINICAL MEDICINE 44 (9-10) 603 -610 1997年12月 [査読無し][通常論文]
   

  Quantifying alkaline phosphatase (ALP) isoenzymes in canine serum would provide a useful index in a clinical laboratory. To achieve this goal, we tested a semi-automatic assay combining wheat germ lectin (WGL) precipitation and chemical inhibition of isoenzymes of the TNS gene with levamisole to quantify bone ALP (BALP) and corticosteroid-induced ALP (CALP), respectively. The liver ALP (LALP) isoenzyme was then calculated from the equation: TALP=BALP+LALP+CALP BALP, LALP and CALP standards from serum of puppies, bile-duct ligated dogs and dogs on 4.4 mg/kg/day prednisolone for 30 days, respectively, were used. The suitability of standard sera was tested by affinity electrophoresis. Levamisole (4.2 mM) inhibits 98% of BALP and LALP but only 42% CALP. Multiplying measured CALP by 1.8 gives the total CALP value in serum. WGL precipitated 92.3% BALP, 23.3% LALP and 26.8% heated CALP standards. These values were used to adjust precipitated ALP ro obtain the exact levels of BALP. WGL was then tested on pooled serum standards in which the relative proportions of all the ALPs were known and controlled. BALP was adequately quantified except when LALP and CALP levels were extremely high. The assay was also applicable under conditions resulting in high ALP. Therefore, combining WGL and levamisole inhibition provides an adequate separation and quantification of canine ALP isoenzymes. The method has great potential for diagnostic use and should be tested further for routine implementation.
• Separation and quantification of corticosteroid-induced, bone and liver alkaline phosphatase isoenzymes in canine serum

  M Syakalima, M Takiguchi, J Yasuda, A Hashimoto JOURNAL OF VETERINARY MEDICINE SERIES A-PHYSIOLOGY PATHOLOGY CLINICAL MEDICINE 44 (9-10) 603 -610 1997年12月 [査読無し][通常論文]
   

  Quantifying alkaline phosphatase (ALP) isoenzymes in canine serum would provide a useful index in a clinical laboratory. To achieve this goal, we tested a semi-automatic assay combining wheat germ lectin (WGL) precipitation and chemical inhibition of isoenzymes of the TNS gene with levamisole to quantify bone ALP (BALP) and corticosteroid-induced ALP (CALP), respectively. The liver ALP (LALP) isoenzyme was then calculated from the equation: TALP=BALP+LALP+CALP BALP, LALP and CALP standards from serum of puppies, bile-duct ligated dogs and dogs on 4.4 mg/kg/day prednisolone for 30 days, respectively, were used. The suitability of standard sera was tested by affinity electrophoresis. Levamisole (4.2 mM) inhibits 98% of BALP and LALP but only 42% CALP. Multiplying measured CALP by 1.8 gives the total CALP value in serum. WGL precipitated 92.3% BALP, 23.3% LALP and 26.8% heated CALP standards. These values were used to adjust precipitated ALP ro obtain the exact levels of BALP. WGL was then tested on pooled serum standards in which the relative proportions of all the ALPs were known and controlled. BALP was adequately quantified except when LALP and CALP levels were extremely high. The assay was also applicable under conditions resulting in high ALP. Therefore, combining WGL and levamisole inhibition provides an adequate separation and quantification of canine ALP isoenzymes. The method has great potential for diagnostic use and should be tested further for routine implementation.
• イヌにおける年齢別の血清中ALP分画活性値の定量及びステロイド誘発性ALP分画活性値の診断的意義

  Syakalima Michelo, 滝口 満喜, 安田 準 The Journal of Veterinary Medical Science 59 (10) 905 -909 1997年10月
• The age dependent levels of serum ALP isoenzymes and the diagnostic significance of corticosteroid-induced ALP during long-term glucocorticoid treatment

  M Syakalima, M Takiguchi, J Yasuda, A Hashimoto JOURNAL OF VETERINARY MEDICAL SCIENCE 59 (10) 905 -909 1997年10月 [査読無し][通常論文]
   

  Three isoenzymes of total alkaline phosphatase (TALP) are known in canine serum: Bone alkaline phosphatase (BALP), liver alkaline phosphatase (LALP) and corticosteroid-induced alkaline phosphatase (CALF). Using an assay developed by combining selective precipitation of BALP by wheat germ lectin (WGA) and an automated levamisole inhibition method for quantifying CALF, age-related reference ranges of the isoenzymes in 75 canine serum samples were investigated. BALP comprised 96, 38 and 26% of TALP in young, middle aged and old dogs, respectively, and CALF was respectively 12, 11 and 27% of TALP. LALP was less than 10% in the young but represented more than 50% of TALP in middle aged and old dogs. Furthermore, the significance of monitoring LALP and CALF and their relationship to hepatopathy in dogs receiving long term prednisolone therapy was assessed. In this study, TALP increased in all dogs receiving prednisolone. But only LALP wits responsible in dogs with minor vacuolization of the liver, while in severely degenerated cases both LALP and CALF increased. It is concluded that a high TALP due solely to LALP, rather than LALP and CALF represents lesser liver pathologic involvement. Monitoring the 2 isoenzymes has greater significancy in assessing the level of liver damage than relying on an increased TALP value alone. Quantifying the individual isoenzymes may further be useful in assessing the clinical significance of these isoenzymes in various conditions that result in elevated TALP values.
• The age dependent levels of serum ALP isoenzymes and the diagnostic significance of corticosteroid-induced ALP during long-term glucocorticoid treatment

  M Syakalima, M Takiguchi, J Yasuda, A Hashimoto JOURNAL OF VETERINARY MEDICAL SCIENCE 59 (10) 905 -909 1997年10月 [査読無し][通常論文]
   

  Three isoenzymes of total alkaline phosphatase (TALP) are known in canine serum: Bone alkaline phosphatase (BALP), liver alkaline phosphatase (LALP) and corticosteroid-induced alkaline phosphatase (CALF). Using an assay developed by combining selective precipitation of BALP by wheat germ lectin (WGA) and an automated levamisole inhibition method for quantifying CALF, age-related reference ranges of the isoenzymes in 75 canine serum samples were investigated. BALP comprised 96, 38 and 26% of TALP in young, middle aged and old dogs, respectively, and CALF was respectively 12, 11 and 27% of TALP. LALP was less than 10% in the young but represented more than 50% of TALP in middle aged and old dogs. Furthermore, the significance of monitoring LALP and CALF and their relationship to hepatopathy in dogs receiving long term prednisolone therapy was assessed. In this study, TALP increased in all dogs receiving prednisolone. But only LALP wits responsible in dogs with minor vacuolization of the liver, while in severely degenerated cases both LALP and CALF increased. It is concluded that a high TALP due solely to LALP, rather than LALP and CALF represents lesser liver pathologic involvement. Monitoring the 2 isoenzymes has greater significancy in assessing the level of liver damage than relying on an increased TALP value alone. Quantifying the individual isoenzymes may further be useful in assessing the clinical significance of these isoenzymes in various conditions that result in elevated TALP values.
• Ultrasonographic appearance of orthotopic ureterocele in a dog

  M Takiguchi, J Yasuda, K Ochiai, Y Morita, A Hashimoto VETERINARY RADIOLOGY & ULTRASOUND 38 (5) 398 -399 1997年09月 [査読無し][通常論文]
   

  A three-year-old, intact male, Siberian husky was evaluated for a two day history of dysuria, Sonographically there was an anechoic cyst-like structure in the urinary bladder, The abnormality appeared to be a 'cyst within a cyst', which is a characteristic ultrasonographic feature of ureterocele in humans, Ultrasonography may be a useful means of establishing a diagnosis of ureterocele in dogs.
• Ultrasonographic appearance of orthotopic ureterocele in a dog

  M Takiguchi, J Yasuda, K Ochiai, Y Morita, A Hashimoto VETERINARY RADIOLOGY & ULTRASOUND 38 (5) 398 -399 1997年09月 [査読無し][通常論文]
   

  A three-year-old, intact male, Siberian husky was evaluated for a two day history of dysuria, Sonographically there was an anechoic cyst-like structure in the urinary bladder, The abnormality appeared to be a 'cyst within a cyst', which is a characteristic ultrasonographic feature of ureterocele in humans, Ultrasonography may be a useful means of establishing a diagnosis of ureterocele in dogs.
• イヌヘルペスウイルス前初期遺伝子の構造

  三好正浩, 滝口満喜, 安田準, 橋本晃, 岡崎克則, 喜田宏 日本獣医学会学術集会講演要旨集 124th 150 1997年09月 [査読無し][通常論文]
  
• 肺包虫症ラットモデルのMRI画像観察

  川原登紀子, 浅沼武敏, 滝口満喜, 安田準, 橋本晃, 桑原幹典, 馬良, 伊藤亮 日本獣医学会学術集会講演要旨集 124th 43 1997年09月 [査読無し][通常論文]
  
• 猫における10%塩酸アルギニン負荷によるインスリン分泌刺激試験

  北村富繁子, 森田豊, 滝口満喜, 安田準, 橋本晃 日本獣医学会学術集会講演要旨集 124th 199 1997年09月 [査読無し][通常論文]
  
• 牛の血清アデノシンデアミナーゼ活性の臨床的意義について

  安田準, 竹馬俊介, 滝口満喜, 橋本晃 日本獣医学会学術集会講演要旨集 124th 200 1997年09月 [査読無し][通常論文]
  
• 超音波内視鏡検査(EUS)の小動物臨床への応用に関する研究 (II) すい管結し犬のすい臓実質エコー輝度のヒストグラム解析

  森田豊, 北村富繁子, 滝口満喜, 安田準, 橋本晃 日本獣医学会学術集会講演要旨集 124th 42 1997年09月 [査読無し][通常論文]
  
• 犬グルココルチコイド誘発性肝障害時におけるアルカリフォスファターゼ(ALP)アイソザイムの肝小葉内分布

  ミチェロ シャカリマ, 滝口満喜, 安田準, 橋本晃 日本獣医学会学術集会講演要旨集 124th 200 1997年09月 [査読無し][通常論文]
  
• 超音波検査が有用であった犬の腸閉塞の3例

  滝口 満喜 北海道獣医師会雑誌 41 (8) 276 -276 1997年08月
• Short-term hemodialysis treatment in dogs and cats with total uretic obstruction

  T Mashita, J Yasuda, M Iijima, M Takiguchi, T Yamazaki, A Hashimoto JAPANESE JOURNAL OF VETERINARY RESEARCH 45 (2) 59 -65 1997年08月 [査読無し][通常論文]
   

  This study evaluated the single-pass system for the short-term dialysis treatment of dogs and cats with experimental renal failure. The hemodialyzer was equipped with a thin and highly permeable Cuprophan membrane. Four animals (two dogs and two cats) with total uretic obstruction were dialyzed twice in a one-week period. The vascular access by venipuncture of external jugular vein delivered more than 5 ml/min/kg/body weight of blood repeatedly, even for the cats. The evaluation of the effects of the blood now, dialysate flow and ultrafiltration pressure revealed that the blood now was the most important factor for effective dialysis. A 300 ml/min dialysate flow provided enough clearance of blood urea nitrogen and creatinine. The ultrafiltration pressure played an important role in ensuring that the fluid removal was constant. Laboratory studies revealed a 50.0% (range 42.0 to 59.3%) reduction of blood urea nitrogen, a 48.7% (range 42.5 to 58.7%) reduction of creatinine, and a 49.8% (range 34.3 to 66.2%) reduction of inorganic phosphate during the dialysis treatment. No dialysis disequilibrium syndrome was shown by the clinical signs. We conclude that this short-term dialysis using a single-pass system for small animals was sufficiently applicable to dogs and cats, and that the optimal duration of the dialysis was 2 hours.
• Short-term hemodialysis treatment in dogs and cats with total uretic obstruction

  T Mashita, J Yasuda, M Iijima, M Takiguchi, T Yamazaki, A Hashimoto JAPANESE JOURNAL OF VETERINARY RESEARCH 45 (2) 59 -65 1997年08月 [査読無し][通常論文]
   

  This study evaluated the single-pass system for the short-term dialysis treatment of dogs and cats with experimental renal failure. The hemodialyzer was equipped with a thin and highly permeable Cuprophan membrane. Four animals (two dogs and two cats) with total uretic obstruction were dialyzed twice in a one-week period. The vascular access by venipuncture of external jugular vein delivered more than 5 ml/min/kg/body weight of blood repeatedly, even for the cats. The evaluation of the effects of the blood now, dialysate flow and ultrafiltration pressure revealed that the blood now was the most important factor for effective dialysis. A 300 ml/min dialysate flow provided enough clearance of blood urea nitrogen and creatinine. The ultrafiltration pressure played an important role in ensuring that the fluid removal was constant. Laboratory studies revealed a 50.0% (range 42.0 to 59.3%) reduction of blood urea nitrogen, a 48.7% (range 42.5 to 58.7%) reduction of creatinine, and a 49.8% (range 34.3 to 66.2%) reduction of inorganic phosphate during the dialysis treatment. No dialysis disequilibrium syndrome was shown by the clinical signs. We conclude that this short-term dialysis using a single-pass system for small animals was sufficiently applicable to dogs and cats, and that the optimal duration of the dialysis was 2 hours.
• アメリカの小動物診療に関する事情

  滝口満喜 北海道獣医師会雑誌 41 (4) 91 -94 1997年04月 [査読無し][通常論文]
  
• 超音波内視鏡検査(EUS)の小動物臨床への応用に関する研究 犬のセルレイン誘発性すい炎のすい臓実質エコー輝度のヒストグラム解析

  森田豊, 北村富繁子, 滝口満喜, 安田準, 橋本晃 日本獣医学会学術集会講演要旨集 123rd 255 1997年03月 [査読無し][通常論文]
  
• Esophageal/gastric adenocarcinoma in a dog

  M Takiguchi, J Yasuda, A Hashimoto, K Ochiai, C Itakura JOURNAL OF THE AMERICAN ANIMAL HOSPITAL ASSOCIATION 33 (1) 42 -44 1997年01月 [査読無し][通常論文]
   

  A nine-year-old, intact female, mixed-breed dog was presented with a history of chronic regurgitation and weight loss. Endoscopy and contrast radiography confirmed the presence of a distal esophageal mass. The dog was euthanized, and histopathological diagnosis of the mass was an esophageal/gastric adenocarcinoma.
• Esophageal/gastric adenocarcinoma in a dog

  M Takiguchi, J Yasuda, A Hashimoto, K Ochiai, C Itakura JOURNAL OF THE AMERICAN ANIMAL HOSPITAL ASSOCIATION 33 (1) 42 -44 1997年01月 [査読無し][通常論文]
   

  A nine-year-old, intact female, mixed-breed dog was presented with a history of chronic regurgitation and weight loss. Endoscopy and contrast radiography confirmed the presence of a distal esophageal mass. The dog was euthanized, and histopathological diagnosis of the mass was an esophageal/gastric adenocarcinoma.
• Ultrasonographic renal changes associated with phenylbutazone administration in three foals

  R Leveille, T Miyabayashi, SE Weisbrode, DS Biller, M Takiguchi, JF Williams CANADIAN VETERINARY JOURNAL-REVUE VETERINAIRE CANADIENNE 37 (4) 235 -236 1996年04月 [査読無し][通常論文]
  
• Ultrasonographic renal changes associated with phenylbutazone administration in three foals

  R Leveille, T Miyabayashi, SE Weisbrode, DS Biller, M Takiguchi, JF Williams CANADIAN VETERINARY JOURNAL-REVUE VETERINAIRE CANADIENNE 37 (4) 235 -236 1996年04月 [査読無し][通常論文]
  
• 猫条虫感染ラットにおける肝臓の超音波画像

  榊原佳美, 滝口満喜, 橋本晃, 安田準, 伊藤亮 日本獣医学会学術集会講演要旨集 121st 109 1996年03月 [査読無し][通常論文]
  
• Ultrasonographic Examination of Cephaloridine (Cer)-Induced Renal Lesions in Rabbits

  Katsuhiko Ishida, Akira Hashimoto, Jun Yasuda, Mitsuyoshi Takiguchi, Kunio Doi Journal of Toxicologic Pathology 9 (3) 273 -276 1996年 [査読無し][通常論文]
   

  Serial ultrasonographic examinations of cephaloridine (CER)-induced renal lesions were performed in rabbits. The nephrosonograms in CER-injected rabbits showed enlarged renal echoic area, increased cortical echogenicity, increased medullary hypoechoic area, and enhanced corticomedullary demarcation. The kidneys in CER-injected rabbits showed macroscopically renal enlargement, cortical discoloration, and medullary enlargement and congestion, and showed histopathologically cortical tubular necrosis, urinary casts in the distal nephrons, and congestion in the outer medulla. These results suggest that drug-induced tubular necrosis is indicated by increased renal cortical echogenicity and that ultrasonographic examination is useful for evaluation of drug-induced nephrotoxicity. © 1996, JAPANESE SOCIETY OF TOXICOLOGIC PATHOLOGY. All rights reserved.
• Ultrasonographic Examination of Cephaloridine (Cer)-Induced Renal Lesions in Rabbits

  Katsuhiko Ishida, Akira Hashimoto, Jun Yasuda, Mitsuyoshi Takiguchi, Kunio Doi Journal of Toxicologic Pathology 9 (3) 273 -276 1996年 [査読無し][通常論文]
   

  Serial ultrasonographic examinations of cephaloridine (CER)-induced renal lesions were performed in rabbits. The nephrosonograms in CER-injected rabbits showed enlarged renal echoic area, increased cortical echogenicity, increased medullary hypoechoic area, and enhanced corticomedullary demarcation. The kidneys in CER-injected rabbits showed macroscopically renal enlargement, cortical discoloration, and medullary enlargement and congestion, and showed histopathologically cortical tubular necrosis, urinary casts in the distal nephrons, and congestion in the outer medulla. These results suggest that drug-induced tubular necrosis is indicated by increased renal cortical echogenicity and that ultrasonographic examination is useful for evaluation of drug-induced nephrotoxicity. © 1996, JAPANESE SOCIETY OF TOXICOLOGIC PATHOLOGY. All rights reserved.
• RADIOGRAPHIC ANATOMY OF THE MEDIAL CORONOID PROCESS OF DOGS

  T MIYABAYASHI, M TAKIGUCHI, SC SCHRADER, DS BILLER JOURNAL OF THE AMERICAN ANIMAL HOSPITAL ASSOCIATION 31 (2) 125 -132 1995年03月 [査読無し][通常論文]
   

  Mediolateral, flexed mediolateral, mediocaudal-laterocranial 15 degrees oblique (extended and supinated mediolateral), and craniolateral-caudomedial 20 degrees to 30 degrees oblique radiographs of 16 elbow-joint specimens were produced to study the radiographic anatomy of the medial coronoid process. On the mediolateral view, the cranial point of the coronoid process was at the level of the distal one-third of the radial epiphysis. Degree of superimposition of the proximal radius and ulna determined how the medial coronoid process was projected on the radiographs. Mediocaudal-laterocranial oblique radiographs best showed the cranial outline of the medial coronoid process with moderate superimposition of the proximal radius and ulna.
• RADIOGRAPHIC ANATOMY OF THE MEDIAL CORONOID PROCESS OF DOGS

  T MIYABAYASHI, M TAKIGUCHI, SC SCHRADER, DS BILLER JOURNAL OF THE AMERICAN ANIMAL HOSPITAL ASSOCIATION 31 (2) 125 -132 1995年03月 [査読無し][通常論文]
   

  Mediolateral, flexed mediolateral, mediocaudal-laterocranial 15 degrees oblique (extended and supinated mediolateral), and craniolateral-caudomedial 20 degrees to 30 degrees oblique radiographs of 16 elbow-joint specimens were produced to study the radiographic anatomy of the medial coronoid process. On the mediolateral view, the cranial point of the coronoid process was at the level of the distal one-third of the radial epiphysis. Degree of superimposition of the proximal radius and ulna determined how the medial coronoid process was projected on the radiographs. Mediocaudal-laterocranial oblique radiographs best showed the cranial outline of the medial coronoid process with moderate superimposition of the proximal radius and ulna.
• 抗血清およびアシクロビルによる新生仔犬の犬ヘルペスウイルス感染症の発病阻止効果

  浅野真知, 滝口満喜, 安田準, 橋本晃, 喜田宏, 平井克哉 日本獣医学会学術集会講演要旨集 119th 235 1995年03月 [査読無し][通常論文]
  
• 新しい臨床診断 キモパパインを用いた髄核融解後のMRI像に関する試験的研究

  滝口満喜, 宮林孝仁 日本獣医学会学術集会講演要旨集 118th 65 1994年08月 [査読無し][通常論文]
  
• 臨床生化学 小動物臨床における尿中酵素の診断的意義

  松岡鎮雄, 真下忠久, 森田豊, 滝口満喜, 安田準, 山崎忠良, SYAKALIMA M, 橋本晃 日本獣医学会学術集会講演要旨集 118th 25 1994年08月 [査読無し][通常論文]
  
• RADIOGRAPHIC APPEARANCES OF THE NASAL CONCHAE IN DOGS USING DIFFERENT SCREEN-FILM SYSTEMS - A POSTMORTEM STUDY

  T MIYABAYASHI, DS BILLER, PR HAIDER, M TAKIGUCHI JOURNAL OF THE AMERICAN ANIMAL HOSPITAL ASSOCIATION 30 (4) 382 -388 1994年07月 [査読無し][通常論文]
   

  Twelve canine heads were radiographed using different intensifying screen-film combinations before and after gelatin instillation within the nasal cavity. The nasal conchal pattern was seen best in nonscreen, radiotherapy localization films. With a fast screen-film system, the conchal pattern was poorly visualized. After gelatin instillation into the nasal cavity, the conchal pattern still was visible on nonscreen films. However, the conchal pattern was more difficult to visualize on a fast screen-film system. Despite substantially increased radiographic exposures, the high diagnostic quality of nonscreen radiographs appeared to warrant their use in evaluating nasal disease. Radiographic changes on a fast screen-film system should be interpreted cautiously for destructive lesions of the nasal cavity.
• RADIOGRAPHIC APPEARANCES OF THE NASAL CONCHAE IN DOGS USING DIFFERENT SCREEN-FILM SYSTEMS - A POSTMORTEM STUDY

  T MIYABAYASHI, DS BILLER, PR HAIDER, M TAKIGUCHI JOURNAL OF THE AMERICAN ANIMAL HOSPITAL ASSOCIATION 30 (4) 382 -388 1994年07月 [査読無し][通常論文]
   

  Twelve canine heads were radiographed using different intensifying screen-film combinations before and after gelatin instillation within the nasal cavity. The nasal conchal pattern was seen best in nonscreen, radiotherapy localization films. With a fast screen-film system, the conchal pattern was poorly visualized. After gelatin instillation into the nasal cavity, the conchal pattern still was visible on nonscreen films. However, the conchal pattern was more difficult to visualize on a fast screen-film system. Despite substantially increased radiographic exposures, the high diagnostic quality of nonscreen radiographs appeared to warrant their use in evaluating nasal disease. Radiographic changes on a fast screen-film system should be interpreted cautiously for destructive lesions of the nasal cavity.
• 犬の椎間板の変性と疾患

  滝口満喜, 宮林孝仁 小動物臨床 13 (2) 13 -18 1994年03月 [査読無し][通常論文]
  
• SCINTIGRAPHIC AND ULTRASONOGRAPHIC DIAGNOSIS OF SOFT-TISSUE INJURY IN A THOROUGHBRED HORSE

  J WILLIAMS, T MIYABAYASHI, A RUGGLES, J YAMAMOTO, M TAKIGUCHI JOURNAL OF VETERINARY MEDICAL SCIENCE 56 (1) 169 -172 1994年02月 [査読無し][通常論文]
   

  A 2.5-year-old female Thoroughbred horse was referred to the veterinary teaching hospital for right front limb lameness of 1 year duration. Physical examination and diagnostic nerve blocks failed to localize the origin of the lameness. Scintigraphy with Tc-99m-MDP suggested increased radionuclide uptake in the palmar metacarpal soft tissues of the right front limb. Ultrasonographic examination revealed hypoechoic lesions in the superficial digital flexor tendon and the suspensory ligament, suggesting tendinitis and desmitis. Combined imaging modalities improved detection and characterization of the cause of a long-standing obscure lameness.
• 犬の椎間板の変性と疾患(共著)

  滝口 満喜, 宮林 孝仁 小動物臨床 13 (2) 13 -18 1994年 [査読無し][通常論文]
  
• Scintigraphic and ultrasonographic diagnosis of soft tissue injury in a thoroughberd horse. "jointly worked"

  J. Vet. Med. Sci. 53 (6) 1019 -1024 1994年 [査読無し][通常論文]
  
• アメリカにおける獣医免許制度について

  宮林孝仁, 滝口満喜 小動物臨床 12 (5) 31 -33 1993年09月 [査読無し][通常論文]
  
• 犬猫の口腔内腫瘍(共著)

  滝口 満喜, 宮林 孝仁 小動物臨床 12 (1) 11 -14 1993年 [査読無し][通常論文]
  
• 犬猫の口腔内腫よう

  滝口満喜, 宮林孝仁 小動物臨床 12 (1) 11 -14 1993年01月 [査読無し][通常論文]
  
• ウマの急性相反応蛋白

  奥村正裕, 山下和人, 平知子, 浅野和之, 布川寧, 滝口満喜, 藤永徹 家畜生化学研究会報 (29) 9 -18 1992年09月 [査読無し][通常論文]
  
• ウマの急性相蛋白（共著）

  家畜生化学研究会報 29: 9-18 1992年 [査読無し][通常論文]
  
• SERUM C-REACTIVE PROTEIN (CRP) IN HORSES - THE EFFECT OF AGING, SEX, DELIVERY AND INFLAMMATIONS ON ITS CONCENTRATION

  K YAMASHITA, T FUJINAGA, M OKUMURA, M TAKIGUCHI, N TSUNODA, S MIZUNO JOURNAL OF VETERINARY MEDICAL SCIENCE 53 (6) 1019 -1024 1991年12月 [査読無し][通常論文]
   

  The serum concentration of C-reactive protein (CRP) in horses was measured by single radial immunodiffusion (SRID) using rabbit anti-equine CRP serum to evaluate the significance of CRP as an acute-phase reactive protein. In serum samples of clinically normal newborn thoroughbred foals before being given colostrum, serum CRP was not detectable (less-than-or-equal-to 1-mu-g/ml). The serum CRP concentration was found to increase quickly and reach a peak level of approximately 14.1-mu-g/ml in 12-month-old horses. Then, it decreased gradually to reach a low value of 5.4-mu-g/ml in the 4-year-old. In horses over 5-year-old, serum CRP concentration was stable at values of 7 to 8-mu-g/ml. In mares during the peri-natal period, serum CRP concentration decreased at 2 months before delivery, showed moderate changes just before and after delivery, and then increased to relatively high level by 2-months after delivery. The concentration of serum CRP was found to be increased at 24 hours after experimentally inflammatory stimuli in adult horses, and reached peak values of 3 to 6 times as high as the base line values at 3 to 5 days. Serum CRP concentration returned to base line values by 2 to 3 weeks after treatments. It is clear from these data that CRP is one of the acute-phase reactive proteins in horses.
• SERUM C-REACTIVE PROTEIN (CRP) IN HORSES - THE EFFECT OF AGING, SEX, DELIVERY AND INFLAMMATIONS ON ITS CONCENTRATION

  K YAMASHITA, T FUJINAGA, M OKUMURA, M TAKIGUCHI, N TSUNODA, S MIZUNO JOURNAL OF VETERINARY MEDICAL SCIENCE 53 (6) 1019 -1024 1991年12月 [査読無し][通常論文]
   

  The serum concentration of C-reactive protein (CRP) in horses was measured by single radial immunodiffusion (SRID) using rabbit anti-equine CRP serum to evaluate the significance of CRP as an acute-phase reactive protein. In serum samples of clinically normal newborn thoroughbred foals before being given colostrum, serum CRP was not detectable (less-than-or-equal-to 1-mu-g/ml). The serum CRP concentration was found to increase quickly and reach a peak level of approximately 14.1-mu-g/ml in 12-month-old horses. Then, it decreased gradually to reach a low value of 5.4-mu-g/ml in the 4-year-old. In horses over 5-year-old, serum CRP concentration was stable at values of 7 to 8-mu-g/ml. In mares during the peri-natal period, serum CRP concentration decreased at 2 months before delivery, showed moderate changes just before and after delivery, and then increased to relatively high level by 2-months after delivery. The concentration of serum CRP was found to be increased at 24 hours after experimentally inflammatory stimuli in adult horses, and reached peak values of 3 to 6 times as high as the base line values at 3 to 5 days. Serum CRP concentration returned to base line values by 2 to 3 weeks after treatments. It is clear from these data that CRP is one of the acute-phase reactive proteins in horses.
• 猫の外傷性口蓋破裂の外科的閉鎖法(共著)

  日本動物病院協会雑誌 22: 12-16 1991年 [査読無し][通常論文]
  
• ISOLATION, CHARACTERIZATION, AND QUANTITATIVE-ANALYSIS OF C-REACTIVE PROTEIN FROM HORSES

  M TAKIGUCHI, T FUJINAGA, M NAIKI, S MIZUNO, K OTOMO AMERICAN JOURNAL OF VETERINARY RESEARCH 51 (8) 1215 -1220 1990年08月 [査読無し][通常論文]
  
• ISOLATION, CHARACTERIZATION, AND QUANTITATIVE-ANALYSIS OF C-REACTIVE PROTEIN FROM HORSES

  M TAKIGUCHI, T FUJINAGA, M NAIKI, S MIZUNO, K OTOMO AMERICAN JOURNAL OF VETERINARY RESEARCH 51 (8) 1215 -1220 1990年08月 [査読無し][通常論文]
  
• イヌの皮下に発生した巨大な血管肉腫の1例

  藤永徹, 諏訪隆彦, 成清美智代, 奥村正裕, 井上久美子, 滝口満喜, 村上正晃, 田島誉士, 大友勘十郎 日本獣医師会雑誌 42 (7) 491 -494 1989年07月 [査読無し][通常論文]
  
• ウマの急性相蛋白に関する研究(1) ウマC-反応性蛋白の分離・精製およびその定量

  滝口 満喜 日本獣医学会学術集会講演要旨集 107回 227 -227 1989年03月
• イヌの皮下に発生した巨大な血管肉腫の１例（共著）

  藤永徹, 諏訪隆彦, 成清美智代, 奥村正裕, 井上久美子, 滝口満喜, 村上正晃, 田島誉士, 大友勘十郎 日獣会誌 42: 491-494 (7) 1989年 [査読無し][通常論文]
  
• Masive subcutaneous hemangiosarcoma in a dog (in Jaoanese with English summary) 'jointly worked'

  J. Jpn. Vet. Assoc. 3 491 -494 1989年 [査読無し][通常論文]
  
• Isolation, characterization, and quantitative analysis of C-reactive protein from horses. "jointly worked"

  Jap. J. Vet. Res. 37 (2) 134 1989年 [査読無し][通常論文]
  
• Masive subcutaneous hemangiosarcoma in a dog (in Jaoanese with English summary) 'jointly worked'

  J. Jpn. Vet. Assoc. 3 491 -494 1989年 [査読無し][通常論文]
  

所属学協会

• 国際獣医放射線学会   日本小動物獣医学会   日本超音波医学会   日本獣医画像診断学会   日本免疫学会   日本獣医学会   

共同研究・競争的資金等の研究課題

• 副腎皮質機能亢進症関連肝障害による肝細胞癌発症機序の解明

  日本学術振興会：科学研究費助成事業

  研究期間 : 2023年04月 -2026年03月 

  代表者 : 滝口 満喜, 村上 正晃, 佐々木 東, 新坊 弦也, 横山 望
• がん特異的代謝システムを標的とした新規セノリティックテラピー開発のための基盤研究

  日本学術振興会：科学研究費助成事業 基盤研究(A)

  研究期間 : 2020年04月 -2025年03月 

  代表者 : 稲波 修, 平岡 和佳子, 安井 博宣, 平田 拓, 滝口 満喜, 岡松 優子

   

  本年度はインビトロの培養細胞の系の実験で、以下の四つの結果が明らかとなった。 1）グルタミン要求性の強いヒト肺がんA549細胞やH460細胞では、放射線照射により、これらの細胞でのグルタミンの取り込みの増大とグルタメートの増大、すなわちグルタミナーゼの活性化を起こす事を明らかにした。さらに、グルタミン代謝阻害剤添加あるいはグルタミン欠乏培地下で培養すると治療線量レベルの放射線照射によって多くの老化様細胞死とSASPの培養液中への分泌を増強させることが可能である事が明らかとなった。 2）グルタミノリシス阻害条件下で放射線による老化様細胞死の誘発機構には活性酸素種の生成量、グルタチオン量の変化DNA損傷の量、さらにはDNA損傷に伴う伴うp53やp21、p16の発現変化などの既知のメカニズムの関与は殆ど無く、未知の機構の関与が示唆されている。 3）更にグルタミノリシス阻害条件下で放射線誘発する老化様細胞死を起こす条件で、Bcl-XL阻害剤ABT-737によって、この増大した老化様細胞死の多くはアポトーシスに変換できること、いわゆるセノリシスを起こせることを明らかにした。 4）一方では、同じ肺がん由来細胞でも786-o細胞ではグルタミン代謝阻害が老化様細胞の増強を起こさず、A549やH460細胞と同様の現象は観察されず、全ての肺がん細胞に於いて同様の機構が働いていない事も明らかとなった。また、脂質代謝阻害剤は老化様細胞増強には関与しなかった。 以上の結果はグルタミン要求性の強い肺がん細胞を中心にその亜致死レベルのグルタミノリシス阻害条件下で治療線量レベルの放射線照射をすると、多量の老化様細胞死の増大が起こす事を示しており、さらに、アポトーシス抑制因子の阻害剤で効率よく老化様細胞死をアポトーシスに変換できることが明確になった。
• 副腎－肝臓連関によるイヌ肝細胞癌発症メカニズムの解明

  日本学術振興会：科学研究費助成事業 基盤研究(B)

  研究期間 : 2020年04月 -2023年03月 

  代表者 : 滝口 満喜, 村上 正晃, 山崎 淳平, 池中 良徳

   

  犬の肝細胞癌における、ステロイドホルモン産生過剰を起点とする発がん仮説の検証を目指し、前年度に引き続いた検討を行った。2年目となる本年度は肝細胞癌・副腎皮質機能亢進症罹患犬における血中ステロイドホルモン・代謝産物のプロファイリング、ならびに肝臓組織でのエピゲノム変異の解析を遂行した。 ステロイドプロファイリングでは前年度に確立した測定系を発展拡大させ、新たに6種の副腎皮質ホルモンと4種の代謝産物を合わせた、合計19種類のステロイドプロファイル解析が可能となった。この新たな測定系を用いて、肝細胞癌36症例、副腎皮質機能亢進症15症例、併発11症例、コントロール19症例を対象として、血液中のステロイドプロファイルを解析した。しかし、血液中のステロイドプロファイルに疾患特異性、もしくは疾患群間での差が認められなかった。 DNAメチル化の解析では、実験的ステロイドホルモン誘発性脂肪肝、副腎皮質腫機能亢進症併発肝細胞癌および肝細胞癌単独症例の腫瘍組織と腫瘍近傍組織の、合計3種類の肝臓組織を用い、多段階発癌仮説の検証を試みた。その結果、脂肪肝・近傍組織・腫瘍組織と段階的なメチル化変化が存在し、腫瘍においてメチル化レベルの高い遺伝子が6、低い遺伝子が12、抽出できた。 現時点では血中ステロイドプロファイルに肝細胞癌と副腎皮質機能亢進症との関連を示唆する血中ステロイドプロファイリングは見つかっていない。一方で、ステロイド肝から腫瘍への段階的なDNAメチル化レベルの変化が存在することが明らかになった。犬の肝細胞癌においてステロイドが発症に役割を果たしていることは十分に予想され、本年度の成果を複合的かつ詳細に解析することで、多段階発がん説の検証が進む。
• 超音波メカノバイオロジーによる神経軸索の伸展制御

  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 -2020年03月 

  代表者 : 滝口 満喜, 佐々木 東, 稲波 修

   

  中枢神経再生の第1ステップである神経突起の伸展と発芽を低強度パルス超音波で制御する試みを行った。ラット初代培養神経細胞に軸索進展阻害因子を作用させ、神経突起を萎縮させた。そこへ低強度パルス超音波を照射し、神経突起の様子を経時的に観察した。低強度パルス超音波により、1つの神経細胞あたりの神経突起は長くなったが、神経突起の起始点の数には変化がなかった。また、生きた細胞の細胞骨格を染色し、低強度パルス超音波照射中の細胞変形の観察に成功した。
• がん特異的グルタミン代謝とアセテート代謝を標的とした新規がん治療法の開発

  日本学術振興会：科学研究費助成事業 基盤研究(B)

  研究期間 : 2017年04月 -2020年03月 

  代表者 : 稲波 修, 安井 博宣, 平田 拓, 滝口 満喜, 山盛 徹

   

  本研究ではがんの放射線治療の新たな代謝標的をあきらかにするために、新しい酸素プローブを用いた電子スピン共鳴法（ESR)を用いたがん代謝のミトコンドリア依存性代謝測定法を確立した。この方法を用いることで多くの固形がんの生存戦略として、グルコース代謝のみならず電子伝達系（ETC）の活性化によるATP産生が放射線照射により増加することを明らかにした。さらにこの放射線誘導エネルギー応答をTCA回路に関与するグルタミノリシスやミトコンドリア阻害剤薬により強い放射線増感を誘導できることを見いだした。特にグルタミンシンターゼ阻害剤やETC阻害薬が強い放射線増感効果を引き起こす事が出来ることを見いだした。
• 動物自然発生腫瘍に対するマイクロバブル併用超音波照射による実用的な新規がん治療

  日本学術振興会：科学研究費助成事業 基盤研究(B)

  研究期間 : 2014年04月 -2017年03月 

  代表者 : 滝口 満喜, 中村 健介, 佐々木 東, 工藤 信樹

   

  超音波による診断と治療の融合の確立に向けた基盤を形成し、臨床応用へと発展させることを目的とし、犬の甲状腺癌および膀胱癌に対する超音波とマイクロバブルを用いた実用的な新規がん治療法「ソノポレーション」に関する前臨床段階の知見を得た。また、ソノポレーションの新たなメカニズムを明らかにすることで、臨床応用の基盤を構築した。
• マイクロバブルと超音波を利用した新しい増感放射線療法の開発

  日本学術振興会：科学研究費助成事業 挑戦的萌芽研究

  研究期間 : 2014年04月 -2016年03月 

  代表者 : 滝口 満喜, 佐々木 東

   

  本研究では、マイクロバブル(MB)存在下での超音波照射に引く続く放射線照射が、放射線誘発アポトーシスの増強効果を示すかを明らかにすることを目的とした。マウス扁平上皮癌細胞にMB存在下で超音波照射直後に放射線を照射した結果、増感比1.1と弱い増感作用を認めた。次いで、超音波による細胞周期変動作用に着目してより効果が期待できる放射線照射の時期を検討したところ、9時間後が最も効果が期待できることが明らかになった。そこで超音波照射後9時間後に放射線を照射したが、増感比は1.1と変わらなかった。平板培養系での超音波照射による細胞の剥離が原因と考えられたため、今後は3次元培養系での検討が必要と思われる。
• 動物自然発生腫瘍に対するマイクロバブル併用超音波照射による実用的な新規がん治療

  文部科学省：科学研究費補助金(基盤研究(B))

  研究期間 : 2014年 -2016年 

  代表者 : 滝口 満喜
• バベシア原虫の増殖および薬剤耐性獲得における熱ショックタンパク質９０の役割の解明

  日本学術振興会：科学研究費助成事業 基盤研究(C)

  研究期間 : 2012年04月 -2015年03月 

  代表者 : 山崎 真大, 大田 寛, 滝口 満喜

   

  本研究では犬の住血寄生原虫であるBabesia gibsoniの熱ショック蛋白質90(BgHsp90)に関する基礎的研究を実施した。BgHsp90の遺伝子をクローニング、塩基配列の解析を行い、抗BgHsp90抗体の作成を行った。これらを用いて遺伝し発現量の測定を行い、BgHsp90が原虫の増殖に貢献していること、原虫が熱ショックを受けたときに発現量が増加することを明らかにした。また、熱ショックタンパク質90阻害薬により、B. gibsoniの増殖を抑制することが可能であり、BgHsp90は治療のターゲットとなることが明らかになった。
• 犬における内臓リーシュマニア症の病態解明と原虫存続機構の分子基盤

  日本学術振興会：科学研究費助成事業 基盤研究(B)

  研究期間 : 2012年04月 -2015年03月 

  代表者 : 片倉 賢, 加藤 大智, 滝口 満喜, 阿戸 学

   

  インド亜大陸の内臓リーシュマニア症の伝播における犬の役割は不明である。本研究では、バングラデシュの本症流行地において、犬のリーシュマニア感染調査を行い、約10％の野犬が抗体陽性あるいは末梢血のPCR陽性であることを明らかにした。次に、実験用ビーグル犬にリーシュマニア原虫を接種して解析した。その結果、臨床症状や血液性状に異常は認められず、また。PCR検査や原虫分離検査も陰性であったが、長期にわたる抗体産生が認められた。以上、Leishmania donovaniに感染した犬は、不顕性感染として原虫を保持する保虫宿主として、内臓リーシュマニ症の伝播に関与している可能性が考えられた。
• マイクロバブルと超音波を利用した新しい増感放射線療法の開発

  文部科学省：科学研究費補助金(挑戦的萌芽研究)

  研究期間 : 2014年 -2015年 

  代表者 : 滝口 満喜
• バベシア原虫の増殖および薬剤耐性獲得における熱ショックタンパク質９０の役割の解明

  文部科学省：科学研究費補助金(基盤研究(C))

  研究期間 : 2012年 -2014年 

  代表者 : 山崎 真大, 大田 寛, 滝口 満喜

   

  犬に感染する赤血球内寄生原虫であるBabesia gibsoniのheat shock protein 90 (hsp90)について、平成25年度は以下の研究を行った。平成24年度には、組み替えhsp90蛋白質の作成のためにプラスミドを作成したが、これを大腸菌内に取り込ませ、大腸菌を用いた組み替えBabesia gibsoni hsp90 (Bghsp90)の発現を実施し、組み替えBghsp90蛋白質の作成に成功した。大腸菌の大量培養を実施することでこれを大量に発現させ、組み替え蛋白質に結合させたHisタグを利用して組み替えBghsp90蛋白質を精製した。さらに、組み替えBghsp90蛋白質をウサギに免疫し、ウサギの体内でこの蛋白質に対する抗血清を作成、さらに抗血清から組み替えBghsp90蛋白質を用いてアフィニティー精製を行ってウサギ抗組み替えBghsp90ポリクローナル抗体を作成した。この抗体がB. gibsoniのhsp90に特異的に結合することを確認した後に、これを用いてウェスタンブロッティングおよび免疫染色を行い、B. gibsoniの持つBghsp90蛋白質を検出、定量することに成功した。そこで、これらの技術を用いて、B. gibsoniの野生株、ならびに抗原虫薬であるジミナゼン製剤に耐性を持つ耐性株のhsp90量を比較し、耐性株ではhsp90発現量が減少していることを明らかにした。この結果は、昨年実施したリアルタイムPCR法を用いた遺伝子発現量の定量を行った実験とよく相関したことから、B. gibsoniのジミナゼン耐性株ではBghsp90の発現量が低下していることが明らかになった。
• 客観的病態診断を可能とする新たな超音波検査法の確立と獣医臨床応用の進展

  日本学術振興会：科学研究費助成事業 基盤研究(C)

  研究期間 : 2011年 -2013年 

  代表者 : 滝口 満喜, 山﨑 真大, 大田 寛

   

  伴侶動物における超音波検査による客観的病態診断の確立に向けた基盤を形成し、その臨床応用の進展を検討することを目的として、まず正常犬の膵臓の灌流状態に関する基礎的知見を得た。次いで、実験的に作出したセルレイン誘発性急性膵炎モデルにおける造影超音波検査所見を解析して、膵臓の血流変化に着目した急性膵炎の新しい診断基準を確立した。 また、左心房機能に着目した心エコー図検査による新たな心機能評価法の確立を目指し、正常犬の左心房面積の時相による変化を解析して正常値を確立するとともに、本手法の再現性を明らかにし、臨床応用への基盤を構築した。
• 客観的病態診断を可能とする新たな超音波検査法の確立と獣医臨床応用の進展

  文部科学省：科学研究費補助金(基盤研究(C))

  研究期間 : 2011年 -2013年 

  代表者 : 滝口 満喜, 山崎 真大, 大田 寛

   

  本研究の目的は、伴侶動物における超音波検査による客観的病態診断の確立に向けた基盤を形成し、その臨床応用の進展を検討することである。まず、超音波造影剤ソナゾイドを用いた造影超音波検査の臨床応用の適用拡大を目的として、未だに診断が困難な膵炎に着目し、正常犬の膵臓の灌流状態に関する基礎的知見を得た。次いで、実験的に作出したセルレイン誘発性急性膵炎モデルにおける造影超音波検査所見を解析して、膵臓の血流変化に着目した急性膵炎の新しい診断基準を確立することを目指した。その結果、超音波造影剤ソナゾイドのボーラス投与(0.01ml/kg)では膵臓の至適観察時間が16秒と短かったため、ソナゾイドを0.05ml/kgで持続点滴することで観察時間を150秒に大幅に延長させる造影検査法を確立した(J Vet Med Sci, 75:1601-1607, 2013) 。また、セルレイン誘発浮腫性膵炎では、正常時に比べて膵実質のエコー輝度のピークまでの到達時間が短縮し、最高輝度が上昇することが明らかとなった(J Vet Intern Med, 28:496-503, 2014) 。これまでソナゾイドを用いた犬の膵臓の造影超音波検査に関する報告は皆無であり、本研究成果によって、犬の膵臓の造影超音波検査法が確立され、実験的に作出した浮腫性膵炎における膵臓の灌流状態の変化の特徴が明らかになったことは、現在進行中の膵炎の臨床例での解析に向けてその礎を築くことができた。臨床例での解析結果も実験膵炎と同様の結果が得られ、本年6月のアメリカ獣医内科学会で発表する予定である。加えて、左心房機能に着目した心エコー図検査による新たな心機能評価法の確立を目指し、正常犬の左心房面積の時相による変化を解析して正常値を確立するとともに、本手法の再現性を明らかにした(Am J Vet Res, 74:864-869)。
• 冬眠動物における腸内細菌叢と腸粘膜バリア:新しい共生様式の解明

  日本学術振興会：科学研究費助成事業 挑戦的萌芽研究

  研究期間 : 2011年 -2012年 

  代表者 : 園山 慶, 坪田 敏男, 滝口 満喜

   

  冬眠動物における腸内細菌の制御と腸粘膜バリアについて解析した。シリアンハムスターの冬眠個体では小腸管腔内の分泌抗体濃度が高く、感染防御に貢献している可能性が考えられた。実際、冬眠ハムスターでは腸間膜リンパ節への細菌の移行は認められなかった。また免疫組織におけるリンパ球プロファイルの解析の結果、冬眠期においても消化管粘膜における感染防御機能および免疫制御機能が維持されていると推察された。さらに、冬眠ハムスターの小腸粘膜上皮における細胞更新が著しく遅滞しており、それにより細胞寿命の延長にともなう細胞老化が生じていることが推察された。
• 冬眠動物における腸内細菌叢と腸粘膜バリア:新しい共生様式の解明

  文部科学省：科学研究費補助金(挑戦的萌芽研究)

  研究期間 : 2011年 -2012年 

  代表者 : 園山 慶, 坪田 敏男, 滝口 満喜

   

  冬眠動物における腸内細菌の制御と腸粘膜バリアについて解析した。シリアンハムスターの冬眠個体では小腸管腔内の分泌抗体濃度が高く、感染防御に貢献している可能性が考えられた。実際、冬眠ハムスターでは腸間膜リンパ節への細菌の移行は認められなかった。また免疫組織におけるリンパ球プロファイルの解析の結果、冬眠期においても消化管粘膜における感染防御機能および免疫制御機能が維持されていると推察された。さらに、冬眠ハムスターの小腸粘膜上皮における細胞更新が著しく遅滞しており、それにより細胞寿命の延長にともなう細胞老化が生じていることが推察された。
• 膜透過性ペプチド融合アポトーシス誘導タンパク質を用いた新規放射線がん治療

  日本学術振興会：科学研究費助成事業 挑戦的萌芽研究

  研究期間 : 2009年 -2010年 

  代表者 : 稲波 修, 滝口 満喜, 山盛 徹

   

  本研究では、p34^-サイクリンB1によるリン酸化部位である34番目のスレオニン(T)をアラニン(A)へ置換したT34A変異サバイビンのN末端に膜透過性ペプチドTAT配列を付加した融合蛋白質を作成し、腫瘍治療におけるTATペプチドによる蛋白質導入技術の有効性と、T34A変異サバイビンのcolon26マウス移植固形腫瘍モデルへの局所投与と放射線照射の併用による抗腫瘍効果について検討した。TATペプチドを付加したサバイビン蛋白質は、腫瘍組織への直接投与で、短時間に腫瘍細胞内へ導入された。X線2Gyの単独照射は、有意な腫瘍の増殖遅延を示さなかった。また、TAT融合T34A変異サバイビンの腫瘍細胞への単独投与も、有意な増殖遅延を示さなかった。一方、X線2GyとTAT融合T34A変異サバイビンの併用は顕著な増殖遅延を示した。組織学的な検索によりX線2GyとTAT融合T34A変異サバイビンの併用による抗腫瘍効果はアポトーシスの誘導によるものであることが示された。さらに、併用により腫瘍組織中の増殖細胞数の減少が観察されたことより、アポトーシス誘導は増殖細胞に特異的に起こることが示唆された。細胞周期関連蛋白質の検出から放射線照射によるG2/M期停止が示唆された。これらの結果から、TAT融合T34A変異サバイビンとX線2Gyの併用による抗腫瘍効果はX線照射で生じる細胞周期チェックポイントに関連したT34A変異サバイビンによるアポトーシス誘導の増強であると考えられた。以上の結果から、TATペプチドによる蛋白質導入技術が腫瘍治療において有効であり、T34A変異サバイビンの投与は腫瘍の放射線治療において、放射線による抗腫瘍作用を増強することが明らかにされた。
• 膜透過性ペプチド融合アポトーシス誘導タンパク質を用いた新規放射線がん治療

  文部科学省：科学研究費補助金(挑戦的萌芽研究)

  研究期間 : 2009年 -2010年 

  代表者 : 稲波 修, 滝口 満喜, 山盛 徹

   

  本研究では、p34^-サイクリンB1によるリン酸化部位である34番目のスレオニン(T)をアラニン(A)へ置換したT34A変異サバイビンのN末端に膜透過性ペプチドTAT配列を付加した融合蛋白質を作成し、腫瘍治療におけるTATペプチドによる蛋白質導入技術の有効性と、T34A変異サバイビンのcolon26マウス移植固形腫瘍モデルへの局所投与と放射線照射の併用による抗腫瘍効果について検討した。TATペプチドを付加したサバイビン蛋白質は、腫瘍組織への直接投与で、短時間に腫瘍細胞内へ導入された。X線2Gyの単独照射は、有意な腫瘍の増殖遅延を示さなかった。また、TAT融合T34A変異サバイビンの腫瘍細胞への単独投与も、有意な増殖遅延を示さなかった。一方、X線2GyとTAT融合T34A変異サバイビンの併用は顕著な増殖遅延を示した。組織学的な検索によりX線2GyとTAT融合T34A変異サバイビンの併用による抗腫瘍効果はアポトーシスの誘導によるものであることが示された。さらに、併用により腫瘍組織中の増殖細胞数の減少が観察されたことより、アポトーシス誘導は増殖細胞に特異的に起こることが示唆された。細胞周期関連蛋白質の検出から放射線照射によるG2/M期停止が示唆された。これらの結果から、TAT融合T34A変異サバイビンとX線2Gyの併用による抗腫瘍効果はX線照射で生じる細胞周期チェックポイントに関連したT34A変異サバイビンによるアポトーシス誘導の増強であると考えられた。以上の結果から、TATペプチドによる蛋白質導入技術が腫瘍治療において有効であり、T34A変異サバイビンの投与は腫瘍の放射線治療において、放射線による抗腫瘍作用を増強することが明らかにされた。
• 自己免疫性唾液線炎におけるB細胞異常増殖の原因遺伝子群と遺伝子間相互作用

  日本学術振興会：科学研究費助成事業 基盤研究(C)

  研究期間 : 2006年 -2008年 

  代表者 : 滝口 満喜, 今野 明弘, 滝口 満善

   

  シェーグレン症候群(Sjogren's syndrome ; SS)モデルIQIマウスにおけるB細胞優勢の下顎腺炎(B細胞性下顎腺炎)を遺伝学的に解析した。その結果、B細胞性下顎腺炎の量的形質遺伝子座(QTL)は少なくとも3個有り、単独で効果を発揮する主要QTL(autoimmune sialitis in IQImice, associated locus 1 ; Asq1)が第6染色体前端に、Asq1の効果を増強するエピスタシスQTLが第3染色体後方(Asq2)に、また、逆にAsq1の効果を抑制する抵抗性遺伝子座が第1染色体後方(Asq3)に位置することを明らかになった。Asq1の1LOD区間内に位置するIca1に注目し、そのcDNA塩基配列を対照C57BL/6(B6)と比較した結果、IQI-B6間で6個の一塩基多型があり、2個のアミノ酸多型が生じていた。また、ウエスタンブロット法では、IQエマウスの血清中に抗Ica1自己抗体の存在を示すバンドカミ検出された。以上の結果より、IQIマウスにおいて、Ica1に対するB細胞自己免疫が成立していることが明らかになり、原因として、1ca1の塩基多型の可能性が挙げられた。
• 自己免疫疾患の新しい分子機構論:中枢性トレランスの破綻による自己への攻撃

  日本学術振興会：科学研究費助成事業 基盤研究(C)

  研究期間 : 2005年 -2006年 

  代表者 : 滝口 満喜, 谷山 弘行, 今野 明弘

   

  高次生体における免疫システムは、外来抗原に対して排除応答を示すが自己抗原に対しては応答しない。この抗原特異的に不応答を示すトレランスは免疫系の重要な特徴で、自己抗原に対するトレランスの破綻は、免疫系による生体自己組織への攻撃と破壊すなわち自己免疫疾患をもたらす。申請者らは、代表的な自己免疫疾患であるシェーグレン症候群(SS)のモデルマウスであるIQI/JicマウスではSSに特徴的な涙腺炎や唾液腺炎などに加え、加齢に伴い膵臓、腎臓、肺などに病変が拡大することを示すとともに、その原因となる自己抗原が臓器特異的なカリクレイン(Klk)13であることをつきとめた。さらに、その発症における末梢性トレランスの関与を調べる目的で、生後3日目に胸腺を摘出して末梢性トレランスを担う制御性T細胞を除外したところ、唾液腺の病変に変化が見られなかったことから、本マウスのSS様病変の形成は末梢性トレランスの破綻によるものではないことを示した。また本マウスではマイトージェン刺激に対するIL-2の産生が顕著に低下しており、これがIL-2遺伝子発現の低下に起因することを確認した。IL-2はin vivoにおいて自己抗原に対する免疫寛容の維持に重要な役割を果たしていることが知られており、これらの結果からT細胞活性化に伴うIL-2の産生低下が本マウスにおける自己寛容の破綻を引き起こし、自己免疫疾患の発症に直接関与している可能性が考えられた。本研究の結果をまとめると、IQI/JicマウスではT細胞の活性化に伴うIL-2産生不全が制御性T細胞とは異なる自己寛容機構を破綻させ、制御性T細胞に依存しない自己寛容の破綻がKlk-13を含む自己抗原に対する持続的な自己反応性T細胞の活性化を引き起こし、唾液腺から他の標的臓器への炎症波及に関与して全身病態の形成に重要な役割を果たすと考えられた。
• 自己免疫疾患の新しい分子機構論:中枢性トレランスの破綻による自己への攻撃

  文部科学省：科学研究費補助金(基盤研究(C))

  研究期間 : 2005年 -2006年 

  代表者 : 滝口 満喜, 谷山 弘行, 今野 明弘

   

  高次生体における免疫システムは、外来抗原に対して排除応答を示すが自己抗原に対しては応答しない。この抗原特異的に不応答を示すトレランスは免疫系の重要な特徴で、自己抗原に対するトレランスの破綻は、免疫系による生体自己組織への攻撃と破壊すなわち自己免疫疾患をもたらす。申請者らは、代表的な自己免疫疾患であるシェーグレン症候群(SS)のモデルマウスであるIQI/JicマウスではSSに特徴的な涙腺炎や唾液腺炎などに加え、加齢に伴い膵臓、腎臓、肺などに病変が拡大することを示すとともに、その原因となる自己抗原が臓器特異的なカリクレイン(Klk)13であることをつきとめた。さらに、その発症における末梢性トレランスの関与を調べる目的で、生後3日目に胸腺を摘出して末梢性トレランスを担う制御性T細胞を除外したところ、唾液腺の病変に変化が見られなかったことから、本マウスのSS様病変の形成は末梢性トレランスの破綻によるものではないことを示した。また本マウスではマイトージェン刺激に対するIL-2の産生が顕著に低下しており、これがIL-2遺伝子発現の低下に起因することを確認した。IL-2はin vivoにおいて自己抗原に対する免疫寛容の維持に重要な役割を果たしていることが知られており、これらの結果からT細胞活性化に伴うIL-2の産生低下が本マウスにおける自己寛容の破綻を引き起こし、自己免疫疾患の発症に直接関与している可能性が考えられた。本研究の結果をまとめると、IQI/JicマウスではT細胞の活性化に伴うIL-2産生不全が制御性T細胞とは異なる自己寛容機構を破綻させ、制御性T細胞に依存しない自己寛容の破綻がKlk-13を含む自己抗原に対する持続的な自己反応性T細胞の活性化を引き起こし、唾液腺から他の標的臓器への炎症波及に関与して全身病態の形成に重要な役割を果たすと考えられた。
• 特定領域研究「動物疾患ジェノミクス」新規創設を目指す企画と調査

  日本学術振興会：科学研究費助成事業 基盤研究(C)

  研究期間 : 2004年 -2004年 

  代表者 : 稲葉 睦, 小川 博之, 国枝 哲夫, 鈴木 勝士, 北川 均, 滝口 満喜

   

  1)学術雑誌等の調査により、過去40年間に国内外で報告された動物の遺伝性疾患、ならびに動物のゲノム解析について、その内容と現在の研究動向を検討した。その概要は、獣医学教科書である「獣医内科学」等に記載のほか、獣医臨床遺伝研究会(平成17年3月)、獣医学会学術集会シンポジウム(平成17年4月)、ならびにHP(平成17年5月開設予定)にて報告する。 2)総括班、調整班が4回の討議を行い、上記を含め以下の合意に達した。 ◆対象とする疾患:特に国内で問題となっている、あるいは特徴的な疾患で、その解析が、産業動物の損耗防止や分子育種につながる牛・豚の疾患、人間社会との共存や福祉の向上に資する犬・猫の疾患、生命科学や基礎医学の基礎理論構築、医療への応用に発展し得る動物疾患。 ◆研究の展開:(1)特定の単一遺伝子疾患の原因遺伝子異常の解析、ならびに発症の分子機構とそれに基づく分子の生理機能の解明。(2)多因子疾患臨床症例の詳細な病態分類と原因となる分子・遺伝子異常の探索。 ◆研究組織:特定領域研究の創設に際しては、臨床知見の集積を含めた研究内容の特性に鑑みて5年間程度の研究展開を目指す。総括班、調整班のもとに上記(1)と(2)の研究展開の基盤となる2〜3の計画研究班を設置して重点的に基礎研究を実施するほか、2年間の公募研究をそれぞれ20件程度ずつ採用する。 2)下記の研究集会、公開シンポジウムを開催し、動物遺伝性疾患概念の周知と研究者-臨床獣医師間交流等を図った。 ◆「近未来の小動物医療-分子医学の潮流-」平成16年9月(札幌)Dr.U.Giger (Univ.Pennsylvania)ら講師4名、参加者約200名。 ◆「臨床遺伝研究会・農水事業・科研費ジョイントフォーラム」平成17年3月(天童)講演者延べ25名、参加者約80名。 これらをもとに、特定領域研究等の具体化を進める。
• 特定領域研究「動物疾患ジェノミクス」新規創設を目指す企画と調査

  文部科学省：科学研究費補助金(基盤研究(C))

  研究期間 : 2004年 -2004年 

  代表者 : 稲葉 睦, 小川 博之, 国枝 哲夫, 鈴木 勝士, 北川 均, 滝口 満喜

   

  1)学術雑誌等の調査により、過去40年間に国内外で報告された動物の遺伝性疾患、ならびに動物のゲノム解析について、その内容と現在の研究動向を検討した。その概要は、獣医学教科書である「獣医内科学」等に記載のほか、獣医臨床遺伝研究会(平成17年3月)、獣医学会学術集会シンポジウム(平成17年4月)、ならびにHP(平成17年5月開設予定)にて報告する。2)総括班、調整班が4回の討議を行い、上記を含め以下の合意に達した。◆対象とする疾患:特に国内で問題となっている、あるいは特徴的な疾患で、その解析が、産業動物の損耗防止や分子育種につながる牛・豚の疾患、人間社会との共存や福祉の向上に資する犬・猫の疾患、生命科学や基礎医学の基礎理論構築、医療への応用に発展し得る動物疾患。◆研究の展開:(1)特定の単一遺伝子疾患の原因遺伝子異常の解析、ならびに発症の分子機構とそれに基づく分子の生理機能の解明。(2)多因子疾患臨床症例の詳細な病態分類と原因となる分子・遺伝子異常の探索。◆研究組織:特定領域研究の創設に際しては、臨床知見の集積を含めた研究内容の特性に鑑みて5年間程度の研究展開を目指す。総括班、調整班のもとに上記(1)と(2)の研究展開の基盤となる2〜3の計画研究班を設置して重点的に基礎研究を実施するほか、2年間の公募研究をそれぞれ20件程度ずつ採用する。2)下記の研究集会、公開シンポジウムを開催し、動物遺伝性疾患概念の周知と研究者-臨床獣医師間交流等を図った。◆「近未来の小動物医療-分子医学の潮流-」平成16年9月(札幌)Dr.U.Giger (Univ.Pennsylvania)ら講師4名、参加者約200名。◆「臨床遺伝研究会・農水事業・科研費ジョイントフォーラム」平成17年3月(天童)講演者延べ25名、参加者約80名。これらをもとに、特定領域研究等の具体化を進める。
• 組織の破壊と低形成-細胞間ジャンクションの分子構築破綻と疾患の遺伝的基盤-

  日本学術振興会：科学研究費助成事業 萌芽研究

  研究期間 : 2003年 -2004年 

  代表者 : 滝口 満喜, 稲葉 睦, 田島 誉士, 高桑 雄一

   

  本研究は、上皮や実質組織の破壊や低形成をともなう多彩な動物疾患の臨床知見の集積と分子病態解析の成果から派生したアイディアに基づくものである。本計画は、"細胞間接合の遺伝的異常と疾患"という新しい観点から、従来、遺伝性素因の存在を疑われながら病因のとらえどころがなかった組織破壊を伴う疾患や臓器低形成の分子機構を解明することを将来目標としている。本萌芽研究では、上記仮説実証の第一歩として、タイトジャンクション(TJ)に分布するCL分子ファミリーに焦点を絞り、まず正常組織における分子群の臓器、組織分布を明らかにし、次いで腎、肝、消化管、皮膚の組織破壊、あるいは低形成を呈する臨床例におけるCL分子の異常を検証することを目的とした。クローディン(CL)分子ファミリーは現在までにヒト、マウスでいずれもCL-1〜CL-18までの18分子種が知られている。代表者らは、これまで牛CL-16に関する解析を行ってきたが、本研究計画では小動物(犬と猫)を対象とするため、まずこれら18種のCLを各々同定するためのツールとして特異抗体を作製することから着手した。犬、猫、個々のCL分子にそれぞれ対応する抗体を作製するのは煩雑であり、また交差性が期待されるため、まず犬CLsに対する抗体を作出、必要に応じて抗猫CLs抗体を作製することとした。抗原として用いる各CL分子C末端ペプチド(C末端の細胞質ドメイン30-40アミノ酸残基)を調製するために、各CL分子のcDNAをRACE法で単離し、GST-融合タンパク質ベクターにクローン化した。cDNA単離に利用する臓器、あるいはプライマーはヒトでの知見に基づいた。GST-融合タンパク質として得た各分子から必要なC末端ペプチドを精製し、ウサギに免疫して、アフィニティー精製によって特異抗体を得た。次いで、イムノブロッティング、ならびに正常組織を用いた蛍光抗体法で反応性と特異性を検定した。臨床例を用いた検討では、様々な疾患でCL分子の局在や発現量に変化が認められたが、現時点では疾患特異的に変動する分子の特定には至らず、今後、さらなる解析が必要である。
• 組織の破壊と低形成-細胞間ジャンクションの分子構築破綻と疾患の遺伝的基盤-

  文部科学省：科学研究費補助金(萌芽研究)

  研究期間 : 2003年 -2004年 

  代表者 : 滝口 満喜, 高桑 雄一, 田島 誉士, 稲葉 睦

   

  本研究は、上皮や実質組織の破壊や低形成をともなう多彩な動物疾患の臨床知見の集積と分子病態解析の成果から派生したアイディアに基づくものである。本計画は、"細胞間接合の遺伝的異常と疾患"という新しい観点から、従来、遺伝性素因の存在を疑われながら病因のとらえどころがなかった組織破壊を伴う疾患や臓器低形成の分子機構を解明することを将来目標としている。本萌芽研究では、上記仮説実証の第一歩として、タイトジャンクション(TJ)に分布するCL分子ファミリーに焦点を絞り、まず正常組織における分子群の臓器、組織分布を明らかにし、次いで腎、肝、消化管、皮膚の組織破壊、あるいは低形成を呈する臨床例におけるCL分子の異常を検証することを目的とした。クローディン(CL)分子ファミリーは現在までにヒト、マウスでいずれもCL-1〜CL-18までの18分子種が知られている。代表者らは、これまで牛CL-16に関する解析を行ってきたが、本研究計画では小動物(犬と猫)を対象とするため、まずこれら18種のCLを各々同定するためのツールとして特異抗体を作製することから着手した。犬、猫、個々のCL分子にそれぞれ対応する抗体を作製するのは煩雑であり、また交差性が期待されるため、まず犬CLsに対する抗体を作出、必要に応じて抗猫CLs抗体を作製することとした。抗原として用いる各CL分子C末端ペプチド(C末端の細胞質ドメイン30-40アミノ酸残基)を調製するために、各CL分子のcDNAをRACE法で単離し、GST-融合タンパク質ベクターにクローン化した。cDNA単離に利用する臓器、あるいはプライマーはヒトでの知見に基づいた。GST-融合タンパク質として得た各分子から必要なC末端ペプチドを精製し、ウサギに免疫して、アフィニティー精製によって特異抗体を得た。次いで、イムノブロッティング、ならびに正常組織を用いた蛍光抗体法で反応性と特異性を検定した。臨床例を用いた検討では、様々な疾患でCL分子の局在や発現量に変化が認められたが、現時点では疾患特異的に変動する分子の特定には至らず、今後、さらなる解析が必要である。
• 犬の自然発生悪性腫瘍を用いた血管新生阻害と分化誘導による腫瘍休眠療法の臨床試験

  日本学術振興会：科学研究費助成事業 基盤研究(B)

  研究期間 : 2002年 -2004年 

  代表者 : 廉澤 剛, 滝口 満喜, 落合 謙爾, 笠岡 達彦, 大泉 巌雄, 日下 雅美, 日下 雅実

   

  悪性腫瘍が自然発生した犬に、血管新生阻害剤TNP-470とサリドマイド、および分化誘導剤OCTを投与し、これらの薬剤の副作用をおもに調べ、さらに可能な範囲で抗腫瘍効果について調べた。 TNP-470は、1回あたり12.5〜223mg/m^2の量で、皮下あるいは静脈内に週1〜3回の割合で投与した。この研究薬は47症例に使用し、副作用と考えられる徴候として、ふらつきあるいは震えが9症例に認められ、次いでけいれん発作が4症例に、出血、食欲低下および嘔吐がそれぞれ1症例に認められた。 サリドマイドは、1回あたり5.0〜20mg/kgの量で毎日経口投与した。この研究薬は、23症例に投与され、副作用と考えられる徴候として、ふらつき、沈鬱あるいは便の軟化が6症例に認められた。 OCTは、1回あたり0.03〜0.12μg/kgの量で毎日経口投与した。この研究薬は、31症例に投与されたが、2週以上にわたり投与された21症例中7症例に高Ca血症が認められた。高Ca血症は休薬によって1週以内に正常に復した。いずれの薬剤においても、副作用と血液検査の変化に重篤なものはなかった。 抗腫瘍効果に関しては、比較対照がないため腫瘍の成長速度や遠隔転移率を抑制しているかを明らかにすることは難しかったが、いくつかの症例で原発巣あるいは転移巣に縮小が認められた。また、高率に転移が生じる骨肉腫などの症例においては、長期にわたって転移が生じない症例も認められた。 以上のことから、今回用いた血管新生阻害剤と分化誘導剤は、従来の抗癌剤と比較して重篤な副作用は極めて少なく、また腫瘍が縮小する症例を認めたことから、腫瘍休眠療法を目指す治療薬としてさらに検討する価値が大きいと思われた。
• 犬の自然発生悪性腫瘍を用いた血管新生阻害と分化誘導による腫瘍休眠療法の臨床試験

  文部科学省：科学研究費補助金(基盤研究(B))

  研究期間 : 2002年 -2004年 

  代表者 : 廉澤 剛, 日下 雅実, 笠岡 達彦, 落合 謙爾, 滝口 満喜, 大泉 巌雄, 日下 雅美

   

  悪性腫瘍が自然発生した犬に、血管新生阻害剤TNP-470とサリドマイド、および分化誘導剤OCTを投与し、これらの薬剤の副作用をおもに調べ、さらに可能な範囲で抗腫瘍効果について調べた。TNP-470は、1回あたり12.5〜223mg/m^2の量で、皮下あるいは静脈内に週1〜3回の割合で投与した。この研究薬は47症例に使用し、副作用と考えられる徴候として、ふらつきあるいは震えが9症例に認められ、次いでけいれん発作が4症例に、出血、食欲低下および嘔吐がそれぞれ1症例に認められた。サリドマイドは、1回あたり5.0〜20mg/kgの量で毎日経口投与した。この研究薬は、23症例に投与され、副作用と考えられる徴候として、ふらつき、沈鬱あるいは便の軟化が6症例に認められた。OCTは、1回あたり0.03〜0.12μg/kgの量で毎日経口投与した。この研究薬は、31症例に投与されたが、2週以上にわたり投与された21症例中7症例に高Ca血症が認められた。高Ca血症は休薬によって1週以内に正常に復した。いずれの薬剤においても、副作用と血液検査の変化に重篤なものはなかった。抗腫瘍効果に関しては、比較対照がないため腫瘍の成長速度や遠隔転移率を抑制しているかを明らかにすることは難しかったが、いくつかの症例で原発巣あるいは転移巣に縮小が認められた。また、高率に転移が生じる骨肉腫などの症例においては、長期にわたって転移が生じない症例も認められた。以上のことから、今回用いた血管新生阻害剤と分化誘導剤は、従来の抗癌剤と比較して重篤な副作用は極めて少なく、また腫瘍が縮小する症例を認めたことから、腫瘍休眠療法を目指す治療薬としてさらに検討する価値が大きいと思われた。
• 赤芽球系分化における膜骨格構築"ユニット工法仮説"の時空間分解分子機構論

  日本学術振興会：科学研究費助成事業 基盤研究(B)

  研究期間 : 2002年 -2003年 

  代表者 : 稲葉 睦, 高桑 雄一, 斉藤 昌之, 前出 吉光, 稲波 修, 山本 雅之, 滝口 満喜

   

  本研究は、赤芽球系細胞における赤血球膜骨格組み込みの"ユニット工法仮説"実証を目的とする。骨髄赤芽球系細胞、赤芽球系培養細胞を用い、遺伝子導入とタンパク質の生化学的・形態学的解析で以下の成果を得た。 ●赤芽球系培養細胞K562を用いて、膜骨格と相互作用する主要膜タンパク質、バンド3、グライコフォリンC、アンキリン、プロテイン4.1、ならびにそれらの変異体の安定発現系を構築し、細胞内局在と赤芽球分化誘導時の挙動や細胞分化・増殖に及ぼす影響を検討した。膜内在性であるバンド3とグライコフォリンCはともにER/Golgiを経て細胞膜に移行した。これらと膜骨格を連結すると考えられるアンキリンとプロテイン4.1も同様にERとGolgiに局在が認められ、これは赤芽球系分化誘導後にも変化しなかった。また、内因性のアンキリンやプロテイン4.1、さらにスペクトリンも主にER/Golgiに分布が認められた。したがって、膜骨格組み込みは赤芽球系細胞の細胞膜ではなく、ERで生じる現象であることが明らかになった。 ●同様の解析で、K562細胞におけるバンド3分子の恒常的発現により細胞増殖速度が約70%に低下すること、誘導剤による赤芽球系分化速度も低下する現象が見出された。しかし、誘導可能な赤芽球までのステージでは、細胞骨格タンパク質の局在や細胞形態に対する影響は認められなかった。 ●骨髄赤芽球系前駆細胞ではスペクトリン等の膜骨格タンパク質の合成とER/Golgiと思われる膜画分への移行がまず生じ、次いでバンド3等の合成と細胞膜での発現が観察された。膜骨格タンパク質の分布は脱核前後で急激に変化した。 以上のように、本研究からは、膜骨格タンパク質の組み込みが細胞内小器官の膜上で既に生じることが明らかになった。ただし、その細胞膜への移行がいわゆる小胞輸送による"ユニット"としてか否かの検証には、新たな手段を講じる必要がある。
• 膜タンパク質のポストゴルジ/ERレトリーバル小胞輸送における新規分子機構の構築

  日本学術振興会：科学研究費助成事業 萌芽研究

  研究期間 : 2002年 -2003年 

  代表者 : 稲葉 睦, 高桑 雄一, 滝口 満喜

   

  本研究の目的は、牛グライコフォリンC(GP-C)の発現、遺伝子型-表現型連関について従来得た以下の仮説を検証し、S85によるポストゴルジ膜移行、あるいはERレトリーバル制御の分子機構を解明することを目的とする。 <仮説1>S85のリン酸化等の翻訳後修飾がポストゴルジ膜移行を決定づける未知のシグナルとして機能している。あるいは、<仮説2>S85を含む周辺配列が未知の膜移行認識シグナルとなっている。仮説1との相乗作用もあり得る。 1.仮説1を検証するために、GST-fused GP-C(C末端細胞質ドメイン)を調製し、これを基質とするProtein kinaseを解析した。その結果、Casein kinase I (CKI)がGP-CのC-末端細胞質ドメインをリン酸化することが判明した。CKIは、遺伝子多型であるS85、N85のGP-Cの両者をリン酸化することから、S85以外のSer/Thr残基もリン酸化されることが推定された。 2.COS細胞、K562細胞におけるGP-C発現系を構築し、それらのリン酸化動態と細胞膜への移行を解析した。これらの細胞ではGP-Cのリン酸化が観察されたが、少なくともCKI阻害剤存在下でのリン酸化の程度は対照と、あるいはGP-CS85とN85とで相違なく、また細胞膜移行の程度にも顕著な差は認められなかった。 3.翻訳後修飾としてO-GlcNAc付加を推定し、その検証を行ったが、O-GlcNAc存在は検出されなかった。 4.仮説2を検証するためにS85を中心にC末端細胞質ドメインのアミノ酸残基を欠く変異体を作製し、培養細胞に導入してその膜移行を解析したところ、むしろにC末端領域を欠く変異体の膜移行が低下することが判明した。これら変異体は、ERに留まり分解除去を受けた。
• 膜タンパク質のポストゴルジ/ERレトリーバル小胞輸送における新規分子機構の構築

  文部科学省：科学研究費補助金(萌芽研究)

  研究期間 : 2002年 -2003年 

  代表者 : 稲葉 睦, 高桑 雄一, 滝口 満喜

   

  本研究の目的は、牛グライコフォリンC(GP-C)の発現、遺伝子型-表現型連関について従来得た以下の仮説を検証し、S85によるポストゴルジ膜移行、あるいはERレトリーバル制御の分子機構を解明することを目的とする。<仮説1>S85のリン酸化等の翻訳後修飾がポストゴルジ膜移行を決定づける未知のシグナルとして機能している。あるいは、<仮説2>S85を含む周辺配列が未知の膜移行認識シグナルとなっている。仮説1との相乗作用もあり得る。1.仮説1を検証するために、GST-fused GP-C(C末端細胞質ドメイン)を調製し、これを基質とするProtein kinaseを解析した。その結果、Casein kinase I (CKI)がGP-CのC-末端細胞質ドメインをリン酸化することが判明した。CKIは、遺伝子多型であるS85、N85のGP-Cの両者をリン酸化することから、S85以外のSer/Thr残基もリン酸化されることが推定された。2.COS細胞、K562細胞におけるGP-C発現系を構築し、それらのリン酸化動態と細胞膜への移行を解析した。これらの細胞ではGP-Cのリン酸化が観察されたが、少なくともCKI阻害剤存在下でのリン酸化の程度は対照と、あるいはGP-CS85とN85とで相違なく、また細胞膜移行の程度にも顕著な差は認められなかった。3.翻訳後修飾としてO-GlcNAc付加を推定し、その検証を行ったが、O-GlcNAc存在は検出されなかった。4.仮説2を検証するためにS85を中心にC末端細胞質ドメインのアミノ酸残基を欠く変異体を作製し、培養細胞に導入してその膜移行を解析したところ、むしろにC末端領域を欠く変異体の膜移行が低下することが判明した。これら変異体は、ERに留まり分解除去を受けた。
• 赤芽球系分化における膜骨格構築"ユニット工法仮説"の時空間分解分子機構論

  文部科学省：科学研究費補助金(基盤研究(B))

  研究期間 : 2002年 -2003年 

  代表者 : 稲葉 睦, 滝口 満喜, 稲波 修, 前出 吉光, 山本 雅之, 高桑 雄一, 斉藤 昌之

   

  本研究は、赤芽球系細胞における赤血球膜骨格組み込みの"ユニット工法仮説"実証を目的とする。骨髄赤芽球系細胞、赤芽球系培養細胞を用い、遺伝子導入とタンパク質の生化学的・形態学的解析で以下の成果を得た。●赤芽球系培養細胞K562を用いて、膜骨格と相互作用する主要膜タンパク質、バンド3、グライコフォリンC、アンキリン、プロテイン4.1、ならびにそれらの変異体の安定発現系を構築し、細胞内局在と赤芽球分化誘導時の挙動や細胞分化・増殖に及ぼす影響を検討した。膜内在性であるバンド3とグライコフォリンCはともにER/Golgiを経て細胞膜に移行した。これらと膜骨格を連結すると考えられるアンキリンとプロテイン4.1も同様にERとGolgiに局在が認められ、これは赤芽球系分化誘導後にも変化しなかった。また、内因性のアンキリンやプロテイン4.1、さらにスペクトリンも主にER/Golgiに分布が認められた。したがって、膜骨格組み込みは赤芽球系細胞の細胞膜ではなく、ERで生じる現象であることが明らかになった。●同様の解析で、K562細胞におけるバンド3分子の恒常的発現により細胞増殖速度が約70%に低下すること、誘導剤による赤芽球系分化速度も低下する現象が見出された。しかし、誘導可能な赤芽球までのステージでは、細胞骨格タンパク質の局在や細胞形態に対する影響は認められなかった。●骨髄赤芽球系前駆細胞ではスペクトリン等の膜骨格タンパク質の合成とER/Golgiと思われる膜画分への移行がまず生じ、次いでバンド3等の合成と細胞膜での発現が観察された。膜骨格タンパク質の分布は脱核前後で急激に変化した。以上のように、本研究からは、膜骨格タンパク質の組み込みが細胞内小器官の膜上で既に生じることが明らかになった。ただし、その細胞膜への移行がいわゆる小胞輸送による"ユニット"としてか否かの検証には、新たな手段を講じる必要がある。
• アポトーシス増強に着目した制癌剤の開発と獣医臨床応用

  日本学術振興会：科学研究費助成事業 基盤研究(C)

  研究期間 : 2000年 -2001年 

  代表者 : 稲波 修, 滝口 満喜, 松田 彰, 桑原 幹典

   

  本研究は、アポトーシスによる細胞死を効率的に引き起こすことを目指したヌクレオシド系増感剤を開発し、獣医領域で問題となるネコ白血病、イヌリンパ腫などの治療のための制がん剤の開発を目的とする。モデル細胞としてヒト胃癌細胞MKN-45細胞とMOLT-4細胞の制がん剤による細胞死の機構を検討した。制がん剤としては1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine(Ecyd)と2'-chrolo-deoxyadenosine(Cl-dAde)を化学合成し、それぞれ検討した。その結果、両細胞ともそれぞれの制がん剤でカスパーゼファミリーの活性化を伴うアポトーシスを効率よく引き起こすことが明らかとなった。そのメカニズムには細胞によって差があり、MKN-45細胞についてはp53依存性のアポトーシスであり、MOLT-4の場合はp53非依存性、Fas活性化依存性のアポトーシスであることが明らかとなった。MKN-45細胞の場合は、蛋白合成に非依存性のカスパーゼ3依存性のアポトーシスを、MOLT-4細胞の場合は、アポトーシス誘導に蛋白質合成を必要とし、FASの活性化、カスパーゼ8を活性化し、カスパーゼ3に依存するアポトーシスを引き起こすことが明らかとなった。この結果は、細胞の種類に依存してアポトーシスを引き起こすシグナル経路の違いを意味している。また、単独では細胞死を起こさない量のEcydで処理した細胞は、放射線照射によって、効率よくネクローシスをアポトーシスに変換できることも明らかとなった。そのメカニズムとして放射線誘発G2期停止のECydによる解除作用が重要であり、G2期解除に伴ってアポトーシスが誘導されることが明かとなった。動物癌細胞への応用という点では、イヌリンパ腫由来CL細胞で、あるいはネコ白血病由来末梢リンパ球でもこれらの薬剤は有用であることが確かめられた。以上の結果は放射線や制癌剤による獣医臨床応用において重要な知見である。
• アポトーシス増強に着目した制癌剤の開発と獣医臨床応用

  文部科学省：科学研究費補助金(基盤研究(C))

  研究期間 : 2000年 -2001年 

  代表者 : 稲波 修, 滝口 満喜, 松田 彰, 桑原 幹典

   

  本研究は、アポトーシスによる細胞死を効率的に引き起こすことを目指したヌクレオシド系増感剤を開発し、獣医領域で問題となるネコ白血病、イヌリンパ腫などの治療のための制がん剤の開発を目的とする。モデル細胞としてヒト胃癌細胞MKN-45細胞とMOLT-4細胞の制がん剤による細胞死の機構を検討した。制がん剤としては1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine(Ecyd)と2'-chrolo-deoxyadenosine(Cl-dAde)を化学合成し、それぞれ検討した。その結果、両細胞ともそれぞれの制がん剤でカスパーゼファミリーの活性化を伴うアポトーシスを効率よく引き起こすことが明らかとなった。そのメカニズムには細胞によって差があり、MKN-45細胞についてはp53依存性のアポトーシスであり、MOLT-4の場合はp53非依存性、Fas活性化依存性のアポトーシスであることが明らかとなった。MKN-45細胞の場合は、蛋白合成に非依存性のカスパーゼ3依存性のアポトーシスを、MOLT-4細胞の場合は、アポトーシス誘導に蛋白質合成を必要とし、FASの活性化、カスパーゼ8を活性化し、カスパーゼ3に依存するアポトーシスを引き起こすことが明らかとなった。この結果は、細胞の種類に依存してアポトーシスを引き起こすシグナル経路の違いを意味している。また、単独では細胞死を起こさない量のEcydで処理した細胞は、放射線照射によって、効率よくネクローシスをアポトーシスに変換できることも明らかとなった。そのメカニズムとして放射線誘発G2期停止のECydによる解除作用が重要であり、G2期解除に伴ってアポトーシスが誘導されることが明かとなった。動物癌細胞への応用という点では、イヌリンパ腫由来CL細胞で、あるいはネコ白血病由来末梢リンパ球でもこれらの薬剤は有用であることが確かめられた。以上の結果は放射線や制癌剤による獣医臨床応用において重要な知見である。
• MRL/lprマウスにおける肺病変発症機序の解明

  日本学術振興会：科学研究費助成事業 奨励研究(A)

  研究期間 : 1999年 -2000年 

  代表者 : 滝口 満喜

   

  本研究の目的は、MRL/lprマウスにおけるCD28/CTLA4-B7補助シグナル非依存性の肺病変について、遺伝背景の異なるマウスを用いることで病変形成に関わる原因遺伝子を探索すること、さらに、肺病変発症機序を解明するために、免疫組織化学的および臨床病理学的に詳細に解析して、病変に関わるサイトカインを同定し、抗サイトカイン抗体の投与実験によってその関わりを証明することである。 まず、MRL/lprに加えて、遺伝背景の異なるC57BL6/lprおよびC3H/He/lprマウスにもCTLA4IgGを生後24時間以内から1回100μg、週3回腹腔内に投与し、20週齢で肺の病理組織学的検索を行った。その結果、MRL/lprではCTLA4IgG投与の有無に関わらず強い肺病変が認められた。C57BL6/lprではCTLA4IgG投与により肺病変が有意に抑制され、C3H/He/lprでは対照と同程度の軽度の単核球浸潤が認められた。以上のことから、CD28/CTLA4-B7補助シグナル非依存性に生じる肺病変は、MRL遺伝背景とともにlpr遺伝子つまり、Fas分子の異常によって誘導されることが示唆された。 次に、MRL/lprマウスの肺病変発症機序の解明を目的として、MRL/lprマウスの肺組織から単核球を分離し、フローサイトメトリーによる解析を行った。表面抗原の解析から、CTLA4IgG投与によってT細胞の活性化は抑制されたが、マクロファージの活性化は抑制されないことが判明した。また、細胞内サイトカインの解析から、マクロファージからのインターフェロンガンマの産生が抑制されないことが明らかとなった。以上の事から、MRL/lprマウスにおけるCD28/CTLA4-B7補助シグナル非依存性に生じる肺病変の形成には、マクロファージから産生されるインターフェロンガンマが関わっていることが示唆された。
• MRL/lprマウスにおける肺病変発症機序の解明

  文部科学省：科学研究費補助金(奨励研究(A))

  研究期間 : 1999年 -2000年 

  代表者 : 滝口 満喜

   

  本研究の目的は、MRL/lprマウスにおけるCD28/CTLA4-B7補助シグナル非依存性の肺病変について、遺伝背景の異なるマウスを用いることで病変形成に関わる原因遺伝子を探索すること、さらに、肺病変発症機序を解明するために、免疫組織化学的および臨床病理学的に詳細に解析して、病変に関わるサイトカインを同定し、抗サイトカイン抗体の投与実験によってその関わりを証明することである。まず、MRL/lprに加えて、遺伝背景の異なるC57BL6/lprおよびC3H/He/lprマウスにもCTLA4IgGを生後24時間以内から1回100μg、週3回腹腔内に投与し、20週齢で肺の病理組織学的検索を行った。その結果、MRL/lprではCTLA4IgG投与の有無に関わらず強い肺病変が認められた。C57BL6/lprではCTLA4IgG投与により肺病変が有意に抑制され、C3H/He/lprでは対照と同程度の軽度の単核球浸潤が認められた。以上のことから、CD28/CTLA4-B7補助シグナル非依存性に生じる肺病変は、MRL遺伝背景とともにlpr遺伝子つまり、Fas分子の異常によって誘導されることが示唆された。次に、MRL/lprマウスの肺病変発症機序の解明を目的として、MRL/lprマウスの肺組織から単核球を分離し、フローサイトメトリーによる解析を行った。表面抗原の解析から、CTLA4IgG投与によってT細胞の活性化は抑制されたが、マクロファージの活性化は抑制されないことが判明した。また、細胞内サイトカインの解析から、マクロファージからのインターフェロンガンマの産生が抑制されないことが明らかとなった。以上の事から、MRL/lprマウスにおけるCD28/CTLA4-B7補助シグナル非依存性に生じる肺病変の形成には、マクロファージから産生されるインターフェロンガンマが関わっていることが示唆された。
• 獣医臨床の診断精度向上に必要な血清・尿中酵素の評価研究

  日本学術振興会：科学研究費助成事業 基盤研究(C)

  研究期間 : 1997年 -1998年 

  代表者 : 安田 準, 滝口 満喜

   

  獣医臨床における自動分析機器使用を前提とした生化学検査の再評価項目として、血清アルカリフォスファターゼ(ALP)アイソザイムとアデノシンデアミナーゼ(ADA)について検討し、犬や乳牛の肝臓や腫瘍疾患における病態診断の精度が向上した。 犬の血清ALPアイソザイム分画をレバミゾール活性阻害法によりコルチコステロイド誘発性アイソザイム(CALP)、レクチン沈殿法により骨性アイソザイム(BALP)を定量することにより、肝性アイソザイム(LALP)も計算で求めて、自動分析機器によるALPアイソザイム分画定量法を確立した。ステロイド長期投与犬におけるLALPとCALPの活性変動と肝臓の組織病理学的変化との関係では、肝細胞の空胞変性が軽度の場合はLALP、重度の場合にはLALPとCALPの活性上昇の関与が明らかとなった。 健康乳牛の血清ADA平均値は5.4IU/lであった。また肉眼的肝臓病変を認めた乳牛の肝臓片と血清とを採取し、肝組織所見とADA値との関連性について検討した。肝組織学的所見を炎症性細胞浸潤の程度で分類し血清ADA活性値を比較したところ、炎症性細胞浸潤の程度が重度である個体ほど高ADA活性を示した。乳牛ではADA特有の病態変動が観察され、肝臓病変の質的な診断意義が示唆された。 健康犬の血中ADA活性の平均値は血清で4.46IU/l、血漿で4.99IU/lであり有意差は認められなかったが、検体の保存条件による変動が大きく、犬の血中ADAは他の動物に較べて非常に不安定であることが示唆された。腫瘍性疾患の血漿ADA活性値はリンパ腫、白血病、肝腫瘍、髄膜腫などの症例で治療開始前のADA活性に上昇が認められ、化学療法開始後は低下する傾向を示した。1年以上寛解が得られているリンパ腫、肺転移腫瘍、腹腔内腫瘍、肥満細胞腫などでは正常範囲内であり、ADAはリンパ系腫瘍の治療経過を観察する上で、病態の指標となりうることが示唆された。
• 獣医臨床の診断精度向上に必要な血清・尿中酵素の評価研究

  文部科学省：科学研究費補助金(基盤研究(C))

  研究期間 : 1997年 -1998年 

  代表者 : 安田 準, 滝口 満喜

   

  獣医臨床における自動分析機器使用を前提とした生化学検査の再評価項目として、血清アルカリフォスファターゼ(ALP)アイソザイムとアデノシンデアミナーゼ(ADA)について検討し、犬や乳牛の肝臓や腫瘍疾患における病態診断の精度が向上した。犬の血清ALPアイソザイム分画をレバミゾール活性阻害法によりコルチコステロイド誘発性アイソザイム(CALP)、レクチン沈殿法により骨性アイソザイム(BALP)を定量することにより、肝性アイソザイム(LALP)も計算で求めて、自動分析機器によるALPアイソザイム分画定量法を確立した。ステロイド長期投与犬におけるLALPとCALPの活性変動と肝臓の組織病理学的変化との関係では、肝細胞の空胞変性が軽度の場合はLALP、重度の場合にはLALPとCALPの活性上昇の関与が明らかとなった。健康乳牛の血清ADA平均値は5.4IU/lであった。また肉眼的肝臓病変を認めた乳牛の肝臓片と血清とを採取し、肝組織所見とADA値との関連性について検討した。肝組織学的所見を炎症性細胞浸潤の程度で分類し血清ADA活性値を比較したところ、炎症性細胞浸潤の程度が重度である個体ほど高ADA活性を示した。乳牛ではADA特有の病態変動が観察され、肝臓病変の質的な診断意義が示唆された。健康犬の血中ADA活性の平均値は血清で4.46IU/l、血漿で4.99IU/lであり有意差は認められなかったが、検体の保存条件による変動が大きく、犬の血中ADAは他の動物に較べて非常に不安定であることが示唆された。腫瘍性疾患の血漿ADA活性値はリンパ腫、白血病、肝腫瘍、髄膜腫などの症例で治療開始前のADA活性に上昇が認められ、化学療法開始後は低下する傾向を示した。1年以上寛解が得られているリンパ腫、肺転移腫瘍、腹腔内腫瘍、肥満細胞腫などでは正常範囲内であり、ADAはリンパ系腫瘍の治療経過を観察する上で、病態の指標となりうることが示唆された。
• 自己免疫疾患の分子機構

  研究期間 : 1998年
• Molecular Mechanism of Autoimmune disease

  研究期間 : 1998年
• 慢性腎疾患の進行に及ぼす摂取蛋白量の影響

  日本学術振興会：科学研究費助成事業 奨励研究(A)

  研究期間 : 1995年 -1995年 

  代表者 : 滝口 満喜

   

  本研究の目的は、外科的に作出した慢性腎不全の猫に対する摂取蛋白量の影響を光学および電子顕微鏡を用いて組織学的に検索するとともに、慢性腎不全の進展因子として注目されている各種サイトカインや成長因子の関わりを検証することであった。 慢性腎不全猫の作出に当たっては、右腎摘出に加え左腎動脈を部分結紮する腎亜全摘モデルの作出を試みたが、高度の手術手技を要することに加えて術後の状態が不安定であったことから、猫に与えるストレスが過大すぎると判断し、腎毒性を有する薬物(ピューロマイシン・アミノヌクレオシド)を投与することで腎障害の誘発を試みた。このピューロマイシン・アミノヌクレオシドはラットに特異的に腎障害を引き起こすことが知られているが、猫での報告はない。そのため、投与量および投与間隔を変えて実験を行う必要があった。その結果、ピューロマイシン・アミノヌクレオシドを猫に投与することによって蛋白尿をきたし、一部の糸球体に硬化病変が誘発されることが示唆された。また、電子顕微鏡によって糸球体上皮細胞足突起の癒合が観察された。血清生化学的にはBUNおよびクレアチニン値に上昇が認められた。尿中酵素ではNAGに変化が認められ、尿中サイトカインではIL-6が病変の進行に伴い増加する傾向が伺えた。 以上のことからピューロマイシン・アミノヌクレオシドは猫に腎障害をもたらすことが示唆された。このモデルにおける病変の進展に及ぼす摂取蛋白量の影響については、現在、実験を継続中である。
• 慢性腎疾患の進行に及ぼす摂取蛋白量の影響

  文部科学省：科学研究費補助金(奨励研究(A))

  研究期間 : 1995年 -1995年 

  代表者 : 滝口 満喜

   

  本研究の目的は、外科的に作出した慢性腎不全の猫に対する摂取蛋白量の影響を光学および電子顕微鏡を用いて組織学的に検索するとともに、慢性腎不全の進展因子として注目されている各種サイトカインや成長因子の関わりを検証することであった。慢性腎不全猫の作出に当たっては、右腎摘出に加え左腎動脈を部分結紮する腎亜全摘モデルの作出を試みたが、高度の手術手技を要することに加えて術後の状態が不安定であったことから、猫に与えるストレスが過大すぎると判断し、腎毒性を有する薬物(ピューロマイシン・アミノヌクレオシド)を投与することで腎障害の誘発を試みた。このピューロマイシン・アミノヌクレオシドはラットに特異的に腎障害を引き起こすことが知られているが、猫での報告はない。そのため、投与量および投与間隔を変えて実験を行う必要があった。その結果、ピューロマイシン・アミノヌクレオシドを猫に投与することによって蛋白尿をきたし、一部の糸球体に硬化病変が誘発されることが示唆された。また、電子顕微鏡によって糸球体上皮細胞足突起の癒合が観察された。血清生化学的にはBUNおよびクレアチニン値に上昇が認められた。尿中酵素ではNAGに変化が認められ、尿中サイトカインではIL-6が病変の進行に伴い増加する傾向が伺えた。以上のことからピューロマイシン・アミノヌクレオシドは猫に腎障害をもたらすことが示唆された。このモデルにおける病変の進展に及ぼす摂取蛋白量の影響については、現在、実験を継続中である。
• 超音波画像診断の応用の多様化と進展に関する研究

  文部科学省：科学研究費補助金(一般研究(B))

  研究期間 : 1994年 -1995年 

  代表者 : 橋本 晃, 滝口 満善, 安田 準

   

  本研究課題の実施計画に基づいて行った2年間で得られた成績は以下に要約できる。1.超音波内視鏡(EUS)の臨床的応用:健康なビ-グル犬を用い、正常消化管および腹部各臓器の抽出方法およびEUS画像の集積を行った。EUSは特に消化管壁、胆嚢および膵臓の抽出に優れていた。セルレイン誘発性の実験的膵炎および人工的に胃壁に作出した血腫や嚢胞のEUSの成績から、膵臓疾患や消化管壁の局在性病変の診断にEUSの有用性が大きいことが明らかにされた。カラードプラ法の併用により、さらに診断精度および病変の質的変化の理解に役立つ情報が得られることが示唆された。以上の成績から、EUSは小動物臨床における有用性が高く、今後のさらなる進展が強く示唆された。2.超音波(US)ガイド下穿刺法の応用:犬のステロイド誘発性肝障害、猫の実験的脂肪肝やピューロマイシン投与による腎障害、さらには前立腺液採取のための二重バルーンカテーテル法の応用に関する研究で、それぞれの標的臓器の経時的な病理組織学的検索にUSガイド下穿刺法による生検を行った成績から、USガイド下穿刺法は小動物の種々臓器の生検に有用であり、応用性の進展が期待できると思われた。3.実験動物へのUSの応用:ウサギを用いたセファロリジン誘発性腎障害の腎病変のUS検査および猫条虫感染ラット肝臓の寄生虫性嚢胞の経時的変化のUS検査で得られた成績から、US検査は実験動物を用いる種々の研究において、新しい解析手技としての有用性、応用性が高いことが明らかにされた。4.小動物における腫瘍症例の画像診断への応用:犬および猫の各種腫瘍にUS診断を行い、多くの画像情報を集積した。またカラードプラ法の併用やUSガイド下穿刺法の併用によって腫瘍の確定診断や腫瘍の質的性状など診断精度の向上に資する成果も得られた。本研究によって得られた成果は、今後の獣医画像診断学の新たな展開に役立つ情報になるであろう。
• 小動物の超音波診断

  研究期間 : 1993年
• 小動物自然発生疾病の画像診断

  研究期間 : 1993年
• Small Animal Dignostic Ultrasound

  研究期間 : 1993年
• Small animal Diagnostic Imaging

  研究期間 : 1993年
• 自己免疫の分子機構
• 自然発生動物疾病の画像診断
• Molecular pathogenesis of autoimmune diseases
• Diagnostic imaging of spontanous animal diseases