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M Isotani,
N Ishida,
M Tominaga,
K Tamura,
H Yagihara,
S Ochi,
R Kato,
T Kobayashi,
M Fujita,
Y Fujino,
A Setoguchi, K Ono,
T Washizu,
M Bonkobara
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ABSTRACT: Imatinib mesylate is a small molecule targeted at dysregulated protein-tyrosine kinase. Mutation of c-kit exon 11, which induces constitutive phosphorylation of KIT, is one of the mechanisms for the development or progression of mast cell tumor (MCT) in dogs. The purpose of this study was to examine the therapeutic potential of imatinib mesylate in canine MCT.
Imatinib mesylate has activity against MCT in dogs, and response to treatment can be correlated to presence of mutation within exon 11 of c-kit.
Twenty-one dogs with MCT with gross tumor burden and median tumor size of 7.2 cm (range, 1.0-25.3 cm) before treatment.
Tumors were analyzed for mutation of c-kit exon 11. Imatinib mesylate was administered PO to the dogs at a dose of 10 mg/kg daily for 1-9 weeks.
Ten of 21 dogs (48%) had some beneficial response to imatinib mesylate treatment within 14 days of treatment initiation. All 5 dogs with a demonstrable c-kit mutation in exon 11 responded to the drug (1 complete remission, 4 partial remission).
Imatinib mesylate has clinical activity against MCT in dogs. Response could not be predicted based on presence of absence of a mutation in exon 11 of c-kit.
Journal of Veterinary Internal Medicine 07/2008; 22(4):985-8. · 1.99 Impact Factor
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The Veterinary record 06/2008; 162(18):592-3. · 1.25 Impact Factor
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ABSTRACT: To establish clinical markers for canine necrotising meningoencephalitis (NME) and to elucidate its pathogenesis, glial fibrillary acidic protein (GFAP) and anti-GFAP autoantibodies were measured in the cerebrospinal fluid (CSF) of 32 dogs with NME, 23 dogs with other inflammatory central nervous system (CNS) diseases, 27 dogs with miscellaneous CNS diseases and 25 healthy dogs, including five pugs. The dogs with NME had the highest levels of anti-GFAP autoantibodies. The diagnostic sensitivity and specificity of anti-GFAP autoantibodies for NME were 91 per cent and 73 per cent, respectively. Some of the dogs with NME and the healthy pugs, had high CSF concentrations of GFAP, suggesting a breed-specific fragility of astrocytes. The leakage of GFAP and the development of autoimmunity may be key to understanding the pathogenesis of NME.
The Veterinary record 09/2007; 161(8):261-4. · 1.25 Impact Factor
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ABSTRACT: The outermost layer of skin, the epidermis, is cornified epithelial tissue composed of keratinocytes. To maintain the structure and function of the epidermis, the regulation of proliferation, differentiation, and cornification of keratinocytes is crucial, and various soluble factors secreted by keratinocytes are involved in these regulations. Previously, work has shown that keratinocytes secreted the protein Kdap (keratinocyte differentiation-associated protein) associated with the formation of cornified cell envelopes, a specialized protective barrier structure on the periphery of terminally differentiating keratinocytes. In the present report, the canine counterpart of human Kdap is identified and an attempt has been made to define its physiological role in canine keratinization. Canine Kdap (cKdap) showed structural features commonly observed in other counterparts and is secreted from transfected cells. The expression profile of cKdap mRNA, which was restrictively expressed in cornified epithelial tissues besides skin has also been determined. These findings indicate that there is a strong association between cKdap expression and cornification, which supports previous observations that Kdap is involved in the synthesis and/or degradation of cornified cell envelopes in humans and mice.
The Veterinary Journal 08/2006; 172(1):141-6. · 2.24 Impact Factor
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ABSTRACT: From the canine genome database and its bioinformatic analysis, we identified conserved sequences within the vast majority of 61 variable segments and 1 joining segment of the immunoglobulin heavy chain (IgH) gene, and designed optimal primers for polymerase chain reaction (PCR) amplification directed at these conserved sequences to evaluate the monoclonality of IgH in canine B cell lymphoma. Using the primers, a PCR-based assay was performed on fine-needle aspiration samples of normal, hyperplasia, and malignant lymph nodes and lymphoma cell lines. All fine-needle aspiration samples of five B cell lymphoma cases and the B cell lymphoma line GL-1 exhibited clonal amplification, whereas no amplification was observed in the samples from normal and hyperplasia lymph nodes, cases of T cell lymphoma, and the T cell lymphoma line CL-1. The primers we designed clearly distinguished malignant B lymphocytes from normal, reactive, and malignant T lymphocytes, indicating a potential utility of the primers for PCR-based routine clinical examination for canine B cell lymphoma.
Veterinary Immunology and Immunopathology 04/2006; 110(1-2):163-7. · 2.08 Impact Factor
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ABSTRACT: The neural-cell adhesion molecule, CD56/N-CAM is a member of the immunoglobulin superfamily expressed by various tissues and cells, including natural killer (NK) cells. Despite the importance of CD56 as a marker for identifying NK cells in circulating blood, canine CD56 has not been identified. In the present study, we identified the canine counterparts of the 140-kDa (CD56-140) and 120-kDa (CD56-120) isoforms of human DC56. Both of amino acid sequences encoded by the canine CD56-140 and -120 cDNA showed high homology with those of human (both 96% homology), having well-conserved domains (five immunoglobulin, two fibronectin type III, and transmembrane and intracellular or glycosylphosphatidylinositol-linked domain) among various species (human, mouse, and feline). We revealed that the transcripts of canine CD56-140 and -120 arise from alternative mRNA splicing from a single gene located on canine chromosome 5. Moreover, the mRNA encoding canine CD56-140 was expressed at high levels constitutively by nervous system and endocrine tissues as has shown in other animals.
Veterinary Immunology and Immunopathology 09/2005; 107(1-2):171-6. · 2.08 Impact Factor
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K Masuda,
M Sakaguchi,
S Fujiwara,
K Kurata,
K Yamashita,
T Odagiri,
Y Nakao,
N Matsuki, K Ono,
T Watari,
A Hasegawa,
H Tsujimoto
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ABSTRACT: Clinically important allergens for the diagnosis and treatment of atopic dermatitis vary geographically. In order to identify the most prevalent allergens in atopic dogs in Japan, 42 dogs with a clinical diagnosis of atopy were tested using both in vivo (intradermal skin test (IDST)) and in vitro (antigen-specific IgE assay) allergy tests. Allergens used for IDST included 26 allergen extracts from eight allergen groups: trees, weeds, grasses, house dust mites (HDM), molds, foods, epithelia, and arthropods. Immunodot assay was used to measure antigen-specific IgE against 24 allergens from these eight groups and against fish such as cod and sole. In the 42 dogs, the most common positive allergen reaction was to HDM on both IDST (29/42 dogs or 69%) and in vitro testing (23/42 or 54.8%). The second most frequent positive allergen reaction was to Japanese cedar pollen (21/42 or 50.0% for IDST and 7/42 or 16.7% for in vitro testing). In both tests, less than 20% of dogs had positive reactions to molds or foods. Positive reactions to cat epithelia were frequently found on IDST, but rarely found on in vitro testing. Agreement between the two tests was found in 26 instances: HDM (21 dogs), Japanese cedar pollen (five dogs) and wheat (one dog). In this study, the two most common allergens involved in atopic dermatitis in dogs in Japan were HDM and Japanese cedar pollen.
Veterinary Immunology and Immunopathology 03/2000; 73(2):193-204. · 2.08 Impact Factor
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ABSTRACT: Elution profiles of total lipoproteins, apolipoprotein B (apoB) concentrations in lipoproteins, and plasma triglyceride (TG) levels were examined in early-, late-, and non-lactating cows. Additionally, arteriovenous (A-V) differences were also measured to elucidate the uptake of TG and apoB-containing lipoproteins in mammary gland. Non-lactating cows showed three major peaks corresponding to triglyceride-rich lipoprotein (TRL), low density lipoprotein (LDL), and high density lipoprotein (HDL) fraction, whereas both early- and late-lactating cows revealed two peaks corresponding to TRL and HDL. The peak area of TRL in early- and late-lactating cows were significantly (p < 0.05) smaller than that in non-lactating cows. The plasma TG levels and apoB-48 concentrations of TRL in early- and late-lactating cows were also significantly (p < 0.01) lower. Furthermore, early lactating cows showed significantly (p < 0.05) larger A-V differences in both plasma TG and apoB-48 concentration of TRL than those in late- and non-lactating cows. These results suggested that TG in exogenous (intestinal) TRL was utilized for milk fat synthesis in lactating mammary gland of cows by the receptor-mediated uptake.
Journal of Veterinary Medical Science 10/1999; 61(10):1143-6. · 0.85 Impact Factor
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ABSTRACT: To mimic exercise-induced events such as energetic impairment, free radical generation, and lipid peroxidation in vitro, mouse-derived C2C12 myotubes were submitted to the inhibition of glycolytic and/or oxidative metabolism with 1 mM iodoacetate (IAA) and/or 2 mM sodium cyanide (CN), respectively, under 5% CO2/95% air up to 180 min. Electron spin resonance (ESR) analysis with a spin-trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) revealed time-course increases in spin adducts from hydroxyl radical (DMPO-OH) and carbon-centered radical (DMPO-R) in the supernatant of C2C12 myotubes treated with the combination of IAA + CN. In this condition, malondialdehyde (MDA) and lactate dehydrogenase (LDH) were released into the supernatant. By the addition of iron-chelating 1 mM deferoxamine to the C2C12 preparation with IAA + CN, both ESR signals of DMPO-OH and DMPO-R were completely abolished, and the release of MDA and LDH were significantly reduced, while cyanide-resistant manganese superoxide dismutase had negligible effects on these parameters. Hence, a part of the injury of C2C12 myotube under IAA + CN was considered to result from the lipid peroxidation, which was induced by hydroxyl radical generated from iron-catalyzed systems such as the Fenton-type reaction. This in vitro model would be a helpful tool for investigating the free radical-related muscle injury.
Free Radical Research 08/1999; 31(1):1-8. · 2.88 Impact Factor
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T Miyazawa,
Y Ikeda,
K Maeda,
T Horimoto,
Y Tohya,
M Mochizuki,
D Vu,
G D Vu,
D X Cu, K Ono,
E Takahashi,
T Mikami
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ABSTRACT: The prevalence of infections with three feline retroviruses (feline immunodeficiency virus (FIV), feline leukemia virus (FeLV) and feline syncytial virus (FSV)) was examined in northern Vietnam in 1997. We collected a total of 77 blood samples from 69 domestic and 8 leopard cats, and examined the presence of anti-FIV and FSV antibodies and FeLV p27 antigen in the plasma samples by the indirect immunofluorescence and/or two commercial kits. None of the samples was positive for FIV and FeLV. The overall positive rate of FSV was 31% and the positive rates among the domestic and leopard cats were 29 and 50%, respectively. We isolated FSV from peripheral blood mononuclear cells of 6 domestic and one leopard cats.
Journal of Veterinary Medical Science 12/1998; 60(11):1273-5. · 0.85 Impact Factor
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ABSTRACT: To characterize the active transport of amino acids across the placenta, uptakes of proline, leucine, and alanine were kinetically examined in placental microvillous membrane vesicles (PMV) prepared from rats in the late gestational period. Uptake rates of these amino acids in PMV showed saturable hyperbolic curves that obeyed Michaelis-Menten kinetics. Proline, leucine, and alanine transport were demonstrated to be carrier mediated systems with sodium-dependent, -independent, and both manner, respectively. In addition, sodium-dependent L-alanine transport showed two different systems, and new sodium-independent alanine transport system (K(m) of 1.12 mM) was observed in rat placenta. From these results, rat placenta has carrier mediated amino acid transport systems, and possesses at least three different transport systems for alanine.
Journal of Veterinary Medical Science 11/1998; 60(10):1081-5. · 0.85 Impact Factor
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ABSTRACT: Two cats with abdominal effusion and anorexia were diagnosed as feline infectious peritonitis (FIP). We tried to evaluate the effect of thromboxane (Tx) synthetase inhibitor, ozagrel hydrochloride, on the progression of symptoms and clinicopathologic data characteristic to FIP. After administration of Tx synthetase inhibitor, improvement of appetite and activity, decreases of peritoneal effusion, reduction of leukocyte number to normal level, and improvement of hyper gamma-globulinemia were found in 2 cats with FIP. These findings suggest that the vasculitis in FIP can be successfully treated with Tx synthetase inhibitor which inhibits platelet aggregation.
Journal of Veterinary Medical Science 06/1998; 60(5):657-9. · 0.85 Impact Factor
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ABSTRACT: The role of mitochondria in the energy metabolism of Babesia microti and Babesia rodhaini was investigated. A variety of mitochondrial inhibitors showed greater sensitivity to B. microti than to B. rodhaini. Additionally, alpha-glycerophosphate- and succinate-cytochrome c reductase activities in the crude mitochondrial fraction from B. microti were substantially higher than those from B. rodhaini. Our results suggest that the mitochondria of these parasites possess a series of "classical" apparati for energy production and their relative functional role may be quantitatively greater in B. microti when compared with B. rodhaini.
International Journal for Parasitology 05/1998; 28(4):567-70. · 3.39 Impact Factor
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ABSTRACT: To elucidate mechanisms of free radical-induced neuronal cell death, lipid peroxidation measured as thiobarbituric acid-reactive substances (TBARS), three antioxidative enzyme activities (superoxide dismutase, glutathione peroxidase, and catalse), and cytosolic free Ca2+ (Ca2+i) were examined in rat hippocampus-derived cells (HV16-4) exposed to free radicals generated by a hypoxanthine-xanthine oxidase system. The viability of cells decreased with an increase in numbers of free radical positive cells in a dose-dependent manner of xanthine oxidase. The protein-bound TBARS did not change, whereas free TBARS increased at 135% of initial value. No remarkable change was observed in three antioxidative enzyme activities. On the other hand, Ca2+i increased after exposure followed by cell death. Furthermore, the addition of Co2+, a nonspecific Ca2+ channel blocker, delayed the increase of Ca2+i and subsequent cell death. These findings suggested that the influx of Ca2+ played a crucial role for HV16-4 cell death induced by free radicals.
Journal of Veterinary Medical Science 02/1998; 60(1):63-9. · 0.85 Impact Factor
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ABSTRACT: To elucidate the pathogenesis of halothane-induced hepatopathy, the changes of hepatic tissue phospholipid peroxidation, malondialdehydes (MDAs), and antioxidative enzyme activities were examined in the portal vein arterialized dogs with halothane inhalation. In group A, which was given halothane inhalation under the hepatic blood flow volume less than 10% of pre-operation volume designated as a hypoxic condition, peroxidized phosphatidylcholine (PC), and free and protein-bound MDA levels significantly increased after inhalation. Although the level of protein bound MDA in group C, given hypoxic condition alone, also increased during the experimental period, the response of this was smaller than that in group A, suggesting that the halothane inhalation enhanced free radical generation under the hypoxic condition. In contrast, no significant changes of these levels were observed in groups B and D, both of which were supplied with sufficient hepatic oxygen as the normoxic condition. In addition, the significant negative correlations between hepatic oxygen supply and total or protein-bound MDA were observed in only halothane inhaled group. These findings suggested that the cause of halothane-induced hepatopathy is closely related to free radicals mainly generated from halothane anaerobic metabolism under the hypoxic condition.
Journal of Veterinary Medical Science 02/1998; 60(1):15-21. · 0.85 Impact Factor
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ABSTRACT: Pregnant rats were subcutaneously administered with mouse epidermal growth factor (EGF) at the concentration of 0, 100, or 200 micrograms/kg body weight/day from day 18 to 21 of gestation. The amino acid analysis by high-performance liquid chromatography demonstrated that the umbilical venous/maternal and fetal/maternal ratio of serum proline concentration increased in EGF dose-dependent manner accompanied by the increase in the ratios of total fetal weight and placental weight to maternal body weight gain. These results suggested that EGF regulates fetal growth by, as one of its possible mechanism, promoting placental proline supply from mother to fetus.
Journal of Veterinary Medical Science 12/1997; 59(11):1053-6. · 0.85 Impact Factor
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ABSTRACT: Hepatic oxygen supply, energy charge (EC), and histology were examined comparatively in dogs with portal vein anastomosis (PVA group), and PA in addition to PVA (PA group). The PVA group showed a lower level of hepatic oxygen supply than those of the PA group throughout the experimental period, and also showed decreases of adenosine triphosphate (ATP) and EC level after blood perfusion. In contrast, the oxygen supply and consumption were stable in the PA group. A temporary fall of ATP level was followed by recovery to the preperfusion level in the PA group. Histological examination indicated the collapse of hepatic cords with granular and vacuolar degeneration in only the PVA group. These findings suggested that PA, when supplemented to PVA, is an available technique for preventing hepatic failure caused by ischemic conditions.
Journal of Veterinary Medical Science 12/1997; 59(11):1057-61. · 0.85 Impact Factor
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ABSTRACT: The concentrations of apolipoprotein B (apoB)-48 and apoB-100 in triglyceride-rich lipoproteins (TRL), intermediate density lipoprotein (IDL), and low density lipoprotein (LDL) fractions separated by gel permeation chromatography were determined in Holstein and Japanese black cows by enzyme-linked immunosorbent assay (ELISA). A significant correlation (p < 0.01) was observed between apoB-48 in TRL and plasma triglyceride (TG) levels in both Holstein and Japanese black cows. Additionally, apoB-48 in TRL and plasma TG levels in Holstein cows were significantly lower (p < 0.01) than those in Japanese black cows. These results suggested that TG derived from intestinal (exogenous) TRL rather than from liver (endogenous) TRL was the major source of milk fat.
Journal of Veterinary Medical Science 09/1997; 59(8):711-4. · 0.85 Impact Factor
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ABSTRACT: To elucidate the role of T cell subpopulations in the protective cell-mediated immune response at the initial phase of infection with Babesia microti (BM) and B. rodhaini (BR), the changes in the course of infection and anti-parasite delayed type hypersensitivity (DTH) response after BM or BR inoculation were investigated in Lyt-2+ T cell or L3T4+ T cell-depleted mice. Depletion of Lyt-2+ T cells strongly enhanced the resistance to BM infection, whereas it increased the susceptibility to BR infection. In contrast, depletion of L3T4+ T cells increased susceptibility to BM infection, while it enhanced resistance to BR infection. The anti-parasite DTH response in BM-infected mice was significantly enhanced by depletion of Lyt-2+ T cells, while significantly reduced by depletion of L3T4+ T cells. No effects of depletion of either Lyt-2+ or L3T4+ cells on DTH response was observed in BR-infected mice. From these results, it was suggested that the roles of Lyt-2+ and L3T4+ T cells in the protective cell-mediated immune response at the initial phase of infection were different between BM- and BR-infected mice, resulting in the difference in their course of infection.
Journal of Veterinary Medical Science 05/1996; 58(4):343-7. · 0.85 Impact Factor
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ABSTRACT: A 12-year neutered male mixed-breed dog was referred to hospital for evaluation of chronic diarrhea. Cellulose acetate electrophoresis of its serum revealed two monoclonal peaks in the gamma-globulin fraction. On immunoelectrophoretic analysis, the two monoclonal peaks in the gamma-globulin region were strongly precipitated with anti-dog IgA serum. On sodium dodecyl sulfate-polyacrylamide gel electrophoretic analysis, the fractions corresponding to these two peaks were shown to be dimer and trimer or tetramer of immunoglobulin consisting of heavy and light chains. These results indicated that the studied dog had gammopathy with two M-components with dimer and trimer or tetramer of IgA. Accumulations of large amounts of these immunoglobulins with very high molecular weight in the serum were concluded to induce the hyperviscosity syndrome in this dog in the terminal stage.
Veterinary Immunology and Immunopathology 12/1995; 49(1-2):161-8. · 2.08 Impact Factor
