著者

Tatsuhito II James K CHAMBERS Ko NAKASHIMA Yuko GOTO-KOSHINO Kazuyuki UCHIDA

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.23-0299, (Released:2023-12-18)

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Differentiating intestinal T-cell lymphoma from chronic enteropathy (CE) in endoscopic samples is often challenging. In the present study, automated machine learning systems were developed to distinguish between the two diseases, predict clonality, and detect prognostic factors of intestinal lymphoma in cats. Four models were created for four experimental conditions: experiment 1 to distinguish between intestinal T-cell lymphoma and CE; experiment 2 to distinguish large cell lymphoma, small cell lymphoma, and CE; experiment 3 to distinguish granzyme B+ lymphoma, granzyme B- lymphoma, and CE; and experiment 4 to distinguish between T-cell receptor (TCR) clonal population and TCR polyclonal population. After each experiment, a pathologist reviewed the test images and scored for lymphocytic infiltration, epitheliotropism, and epithelial injury. The models of experiments 1–4 achieved area under the receiver operating characteristic curve scores of 0.943 (precision, 87.59%; recall, 87.59%), 0.962 (precision, 86.30%; recall, 86.30%), 0.904 (precision, 82.86%; recall, 80%), and 0.904 (precision, 81.25%; recall, 81.25%), respectively. The images predicted as intestinal T-cell lymphoma showed significant infiltration of lymphocytes and epitheliotropism than CE. These models can provide evaluation tools to assist pathologists with differentiating between intestinal T-cell lymphoma and CE.

著者

Hiroto TOYODA Akiyoshi TANI Yuko GOTO-KOSHINO Tomoki MOTEGI Mika SAKAMOTO Takako MOCHIZUKI Kei HARADA Tetsuya KOBAYASHI Asuka SETOGUCHI Yohei SHIZUTA Takuya MIZUNO Mitsuhiro IRIE Jun NAKAMICHI Hajime TSUJIMOTO Aki OHMI Ray FUKUOKA Yasukazu NAKAMURA Hirotaka TOMIYASU

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.23-0269, (Released:2023-11-13)

被引用文献数

1

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Although chemotherapy using CHOP-based protocol induces remission in most cases of canine multicentric high-grade B-cell lymphoma (mhBCL), some cases develop early relapse during the first induction protocol. In this study, we examined the gene expression profiles of canine mhBCL before chemotherapy and investigated their associations with early relapse during the first whole CHOP-based protocol. Twenty-five cases of mhBCL treated with CHOP-based protocol as first induction chemotherapy were included in this study. Sixteen cases completed the first whole CHOP-based protocol without relapse (S-group), and nine developed relapse during the chemotherapy (R-group). RNA-seq was performed on samples from neoplastic lymph nodes. Differentially expressed genes (DEGs) were extracted by the comparison of gene expression profiles between S- and R-groups, and the differences in the expression levels of these genes were validated by RT-qPCR. Extracted 179 DEGs included the genes related to chemokine CC motif ligand, T-cell receptor signaling pathway, and PD-L1 expression and PD-1 checkpoint pathway. We focused on chemokine CC motif ligand, and CCL4 was confirmed to be significantly downregulated in the R-group (P=0.039). We also focused on the genes related to T-cell signaling pathway, and CD3E (P=0.039), ITK (P=0.023), and LAT (P=0.023) genes were confirmed to be significantly upregulated in the R-group. The current results suggest that both changes in tumor cells and the interactions between tumor cells and immune cells are associated with the efficacy of the chemotherapy for first remission induction.

著者

Riho SHIKANO Koichi OHNO Takuro NAGAHARA Itsuma NAGAO Hiroto TOYODA Taisuke NAKAGAWA Yuko GOTO-KOSHINO James K. CHAMBERS Hirotaka TOMIYASU Hajime TSUJIMOTO

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.22-0126, (Released:2022-09-08)

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The associations of diet compositions with mucin secretion in gallbladder have not been investigated in dogs. This study aimed to examine the effects of a low-carbohydrate diet (LC) and a low-fat diet (LF) on bile mucin concentration and composition of gallbladder bile in six clinically healthy beagle dogs. After feeding of both diets, the bile mucin concentration was significantly decreased. In addition, there were significant decreases in the concentrations of taurochenodeoxycholic acid in bile, which is considered to promote mucin secretion, after feeding of both diets. The present study suggested that the proportions of carbohydrate and fat in diet affect the composition of gallbladder bile in dogs.

著者

Takuro NAGAHARA Koichi OHNO Itsuma NAGAO Taisuke NAKAGAWA Yuko GOTO-KOSHINO Masaya TSUBOI James K. CHAMBERS Kazuyuki UCHIDA Hirotaka TOMIYASU Hajime TSUJIMOTO

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.21-0257, (Released:2022-03-14)

被引用文献数

1

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Intestinal lymphangiectasia (IL) is often observed in dogs with chronic small intestinal diseases. Hypoplasia of the lymphatic vessel due to decreased lymphangiogenesis, which has been suggested in human idiopathic IL, may contribute to the pathogenesis of canine IL. This study aimed to evaluate the diameter and number of lymphatic vessels in full-thickness small intestinal specimens of dogs with IL. Immunohistochemical labeling of lymphatic endothelial cell markers was performed on retrospectively retrieved full-thickness small intestinal specimens. Sixteen dogs with histologically confirmed IL were included, of which 10 had lymphoplasmacytic enteritis (LPE), and six had granulomatous lymphangitis (GL). Nine dogs that died from non-gastrointestinal disorders and with little or no abnormalities in the small intestine were used as controls. Lymphatic vessel diameters in dogs with IL were significantly increased in all layers of the small intestine, including the villus lacteal, lamina propria, submucosa, muscularis, and mesentery, compared with controls (all P<0.01). There was no significant difference in the lymphatic vessel diameters between dogs with LPE and GL (all P>0.05). There was no significant difference in the number of lymphatic vessels between dogs with IL and the controls in all layers of the small intestine (all P>0.05). This study demonstrated that IL was observed in all layers of the small intestine, including the submucosa, muscularis, and mesentery, independent of the underlying disease. Factors other than reduced lymphatic vessels would contribute to the pathogenesis of IL in dogs.

著者

Takuro NAGAHARA Koichi OHNO Itsuma NAGAO Taisuke NAKAGAWA Yuko GOTO-KOSHINO Masaya TSUBOI James K. CHAMBERS Kazuyuki UCHIDA Hirotaka TOMIYASU Hajime TSUJIMOTO

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.21-0363, (Released:2021-12-01)

被引用文献数

1

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Intestinal lymphangiectasia (IL) is a common complication in dogs. Since nitric oxide (NO) is known to relax the lymphatic duct, we evaluated inducible NO synthase (iNOS) expression using immunohistochemistry in 13 dogs with lymphoplasmacytic enteritis (LPE) with or without IL. The duodenal iNOS expressing cells were significantly increased in dogs with IL-negative or IL-positive LPE dogs (P=0.025, P=0.007) compared with control dogs. However, there was no significant difference in iNOS expression between IL-positive and IL-negative tissues. Based on these results, there is no clear evidence for the NO overproduction in the pathogenesis of IL in dogs with LPE. Factors other than NO could, thus, contribute to IL in dogs with LPE.

著者

Takuro NAGAHARA Koichi OHNO Itsuma NAGAO Taisuke NAKAGAWA Nozomu YOKOYAMA Aki OHMI Yuko GOTO-KOSHINO James K. CHAMBERS Kazuyuki UCHIDA Hirotaka TOMIYASU Hajime TSUJIMOTO

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.21-0137, (Released:2021-06-28)

被引用文献数

1

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Protein-losing enteropathy (PLE) is known to induce hypercoagulability and resultant thromboembolism in dogs. We hypothesized that hypercoagulability would improve if remission was obtained in dogs with PLE after treatment. This study aimed to evaluate the changes in the coagulation parameters after treatment in dogs diagnosed with PLE. As coagulation parameters, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, thrombin-antithrombin complex (TAT), D-dimer, and antithrombin (AT) were measured. In addition to these parameters, rotational thromboelastometry (ROTEM), which evaluates the comprehensive coagulation and fibrinolysis reactions of whole blood, was conducted and the data of clotting time (CT), clot formation time (CFT), α angle (α), maximum clot firmness (MCF) and lysis index at 60 min (LI60) were obtained. Eleven of the 14 dogs diagnosed with PLE were classified as responders to the treatment based on the changes in their plasma albumin (ALB) concentration after treatment. Significant increase in CFT and decrease of α and MCF indicating the resolution of hypercoagulability were found after treatment in responder dogs; however, there was no significant change in the coagulation and fibrinolysis parameters other than those measured by ROTEM. This study demonstrated that the hypercoagulability detected by ROTEM was significantly improved after treatment in dogs with PLE.

著者

Maho NAKAZAWA Hirotaka TOMIYASU Kanako SUZUKI Hajime ASADA Aki FUJIWARA-IGARASHI Yuko GOTO-KOSHINO Aki OHMI Koichi OHNO Michio FUJITA Hajime TSUJIMOTO

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

vol.83, no.3, pp.456-460, 2021 (Released:2021-04-03)

参考文献数

20

被引用文献数

6

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Nasal lymphoma (NL) is the most common nasal tumor in cats, and radiotherapy, chemotherapy, or a combination of these treatments have been described as the treatment for this disease. However, the previous studies included various machines and protocols of radiotherapy. Therefore, we aimed to retrospectively compare the prognosis among cases treated with palliative hypofractionated radiotherapy, chemotherapy, and a combination of them with united machine and protocol of radiotherapy. When compared overall survival and progression free survival, there was no significant difference among these three groups. The data of this study suggested that similar efficacy could be achieved by palliative hypofractionated radiotherapy, chemotherapy, or a combination of them.

著者

Akiyoshi TANI Taisuke SENO Nozomu YOKOYAMA Taisuke NAKAGAWA Hirotaka TOMIYASU Yuko GOTO-KOSHINO Hajime TSUJIMOTO Koichi OHNO

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.19-0560, (Released:2020-02-14)

被引用文献数

1

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Inflammatory colorectal polyps (ICRPs) are frequently observed in miniature dachshunds in Japan and treated by prednisolone and immunosuppressive drugs such as cyclosporine and leflunomide. The purpose of this retrospective study was to compare the treatment efficacy, such as response rate, response interval, recurrence rate, and adverse events between cyclosporine and leflunomide. While the response rates were significantly higher in dogs treated with leflunomide, no significant differences were observed in the response interval or recurrence rate. Two of the 11 dogs treated with leflunomide showed hematological or gastrointestinal adverse events, while no dog treated with cyclosporine showed any adverse events. A case-controlled prospective study to compare the treatment efficacy of leflunomide with that of cyclosporine should be conducted.

著者

Itsuma NAGAO Koichi OHNO Takuro NAGAHARA Nozomu YOKOYAMA Taisuke NAKAGAWA Reina FUJIWARA Kie YAMAMOTO Yuko GOTO-KOSHINO Hirotaka TOMIYASU Hajime TSUJIMOTO

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.19-0254, (Released:2019-09-25)

被引用文献数

4

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In human medicine, computed tomography (CT) is the gold standard for visceral fat measurement. Research shows that the visceral fat area (VFA) of the umbilical slice is significantly correlated with the visceral fat volume (VFV). In veterinary medicine, however, few studies have evaluated visceral fat using CT. This study aimed to evaluate the visceral fat in dogs using CT images, and determine if the slice significantly correlated with VFV to simplify visceral fat measurements. This retrospective study includes data on 90 dogs that underwent whole-body CT scans for diagnostic purposes. VFV was calculated as the product of VFA and thickness in each CT slice; the correlation between VFV and VFA was analyzed at the level of each lumbar vertebra. Visceral fat percentage (VF%) was calculated as the ratio of the product of VFV and fat density to the body weight. Visceral fat area percentage (VFA%) was calculated as the ratio of VFA to the body area, and its correlation with the VF% and the body condition score (BCS) was analyzed. VFA was highly correlated with VFV at the level of each lumbar vertebra, with the highest correlation (r=0.964) at the L3 level. VFA% was significantly correlated with VF% (r=0.930) and weakly correlated with BCS (r=0.523). This study demonstrates that it is sufficient to use only the L3 slice for visceral fat evaluation and that the evaluation can be based on VFA% of the L3 level.

著者

Hiroki YAMAZAKI Naoki MIURA Yu-Chang LAI Masashi TAKAHASHI Yuko GOTO-KOSHINO Momoi YASUYUKI Munekazu NAKAICHI Hajime TSUJIMOTO Asuka SETOGUCHI Yasuyuki ENDO

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

vol.79, no.7, pp.1225-1229, 2017 (Released:2017-07-19)

参考文献数

20

被引用文献数

8

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We examined whether multidrug resistant (MDR) canine lymphoma increases gene expression for platelet-derived growth factor receptor α (PDGFRα), vascular endothelial growth factor receptor 2 (VEGFR2), and c-KIT, and whether toceranib phosphate (TOC) has potential as a treatment for MDR canine lymphoma. The clinical data showed that PDGFRα expression was higher in canine subjects with MDR T-cell lymphoma than in those with untreated T-cell lymphoma, and that c-KIT expression was greater in subjects with T-cell lymphoma than in those with B-cell lymphoma. TOC monotherapy was well tolerated without serious adverse effects, and two of the five subjects that received TOC exhibited partial responses. The data presented here could contribute to the assessment of TOC-based therapy for dogs with MDR or T-cell lymphoma.

著者

Hajime ASADA Masaya TSUBOI James K. CHAMBERS Kazuyuki UCHIDA Hirotaka TOMIYASU Yuko GOTO-KOSHINO Koichi OHNO Hajime TSUJIMOTO

出版者

公益社団法人 日本獣医学会

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.17-0197, (Released:2017-09-01)

被引用文献数

12

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Canine histiocytic sarcoma (HS) is a malignancy originating from the histiocytic cell lineage and characterized by poor response to chemotherapy and short survival time. Mutation of the TP53 gene and its association with poor prognosis has been reported in several canine tumors. However, the mutation of this gene has not been investigated in canine HS. The aim of this study was to examine a TP53 gene mutation in dogs with HS. Aberrations of the TP53 gene were examined by polymerase chain reaction-single strand conformational polymorphism analysis and DNA sequence analysis, revealing mutations of the TP53 gene in 12 (46%) of 26 dogs affected by HS. The incidence of the TP53 gene mutation was relatively high in canine HS compared with other canine tumors. Among these mutations, 10 of 12 dogs (83%) with a TP53 gene mutation harbored the same mutation: a 2-base (AT) insertion in exon 5, resulting in the introduction of a stop codon (c.446_447insAT, p.Tyr150SerfsX8). Further studies are needed to examine the functional change due to the mutation and its association with the pathogenesis of canine HS.

著者

Aki OHMI Koichi OHNO Kazuyuki UCHIDA Yuko GOTO-KOSHINO Hirotaka TOMIYASU Hideyuki KANEMOTO Kenjiro FUKUSHIMA Hajime TSUJIMOTO

出版者

公益社団法人 日本獣医学会

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.16-0626, (Released:2017-08-05)

被引用文献数

11

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Shiba dogs are predisposed to chronic enteropathy (CE) and have poorer prognosis than other dog breeds. The objective of this study was to investigate the significance of polymerase chain reaction for antigen receptor rearrangement (PARR) results on clinical findings and prognosis of Shiba dogs with CE. We retrospectively collected data on 22 Shiba dogs diagnosed as having CE. Fifty-nine percent of the dogs had clonality-positive results on PARR analysis. Furthermore, on histopathology, epitheliotropic behavior of small lymphocytes of the intestinal mucosa was observed significantly more frequently in dogs with clonal rearrangement of antigen receptor genes (P=0.027). The median overall survival time of clonality-positive dogs was 48 days (range, 4–239 days), compared to 271 days (range, 45–1,316+ days) in clonality-negative dogs. The median overall survival time of epitheliotropism-positive dogs was 76 days (range, 30–349 days) compared to 239 days (range, 4–1,316+ days) for epitheliotropism-negative dogs. Statistical analysis revealed that the clonality-positive result was associated with significantly shorter survival time (P=0.036). In contrast, presence or absence of epitheliotropism had no statistically significant effect on survival time (P=0.223). These cases might appropriately be diagnosed as small T-cell intestinal lymphoma; there are some common clinical and pathogenic features with human enteropathy-associated T-cell lymphoma type 2. The pathogenesis and poor prognosis for Shiba dogs with CE seem to be associated with this type of lymphoma, although further investigation is warranted.

著者

Toru SATO Koichi OHNO Takashi TAMAMOTO Mariko OISHI Hideyuki KANEMOTO Kenjiro FUKUSHIMA Yuko GOTO-KOSHINO Masashi TAKAHASHI Hajime TSUJIMOTO

出版者

公益社団法人 日本獣医学会

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.16-0009, (Released:2016-09-23)

被引用文献数

37

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Canine pancreatitis is a relatively common disorder, and its mortality rate remains high. However, prognostic factors for pancreatitis based on evidence are limited. Moreover, the relationship between changes in C-reactive protein (CRP) concentration—an important prognostic factor for human patients with acute pancreatitis—and the prognosis of dogs with pancreatitis has not been widely studied. Therefore, we examined prognostic factors for canine pancreatitis during the first medical examination and evaluated the usefulness of serial CRP measurements during hospitalization. Sixty-five dogs met the inclusion criteria, including 22 that were hospitalized and treated. In study 1, a multivariate analysis revealed that three factors— decreased platelet count and a marked (greater than 1,000 μg/l) elevation of specific canine pancreatic lipase (Spec cPL) concentration at the first medical examination, as well as elevated blood urea nitrogen (BUN) and/or creatinine (CRE) level—were significantly different between the survivors and nonsurvivors. Moreover, CRP concentrations on the third and fourth days were significantly different between the two groups in study 2. An evaluation of the decreased platelet count, remarkable elevation of Spec cPL concentration at the first medical examination, elevation of BUN and/or CRE as well as serial CRP concentration measurements may be useful for predicting the prognosis of canine pancreatitis.

著者

Noriyuki MIZUTANI Yuko GOTO-KOSHINO Masashi TAKAHASHI Kazuyuki UCHIDA Hajime TSUJIMOTO

出版者

公益社団法人 日本獣医学会

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.15-0688, (Released:2016-04-21)

被引用文献数

1 33

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Clinical and histopathological characteristics of 16 dogs with nodal paracortical (T-zone) lymphoma (TZL) were evaluated. At initial examination, generalized lymphadenopathy was found in all dogs, and peripheral lymphocytosis was found in 10 of the 16 dogs. At initial diagnosis or during the disease course, 8 dogs (50%) were affected with demodicosis. Immunohistochemical analysis for CD3, CD20 and CD25 was performed for 6 dogs with TZL; the tumor cells were positive for CD3 and CD25 and negative for CD20. Median overall survival time was 938 days. A watchful waiting approach was adopted for 6 cases (38%), and 5 of the 6 dogs were still alive at the end of follow-up. The clinical course of TZL in dogs is generally indolent; however, many cases develop a variety of infectious and other neoplastic diseases after the diagnosis of TZL.

著者

Hirotaka IGARASHI Koichi OHNO Aki FUJIWARA-IGARASHI Hideyuki KANEMOTO Kenjiro FUKUSHIMA Yuko GOTO-KOSHINO Kazuyuki UCHIDA Hajime TSUJIMOTO

出版者

公益社団法人 日本獣医学会

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.14-0505, (Released:2014-12-20)

被引用文献数

3 12

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Inflammatory colorectal polyps (ICRPs) frequently occur in miniature dachshunds (MDs) in Japan. MDs with ICRPs develop multiple polyps with severe neutrophil infiltration that respond to immunosuppressive therapy. Therefore, ICRPs are thought to constitute a novel, breed-specific form of canine inflammatory bowel disease (IBD). Pattern recognition receptors (PRRs) play a key role in the distinction of pathogens from commensal bacteria and food antigens. Dysfunction resulting from genetic disorders of PRRs have been linked to human and canine IBD. Therefore, we analyzed the reactivity of PRRs in MDs with ICRPs. Twenty-six MDs with ICRPs and 16 control MDs were recruited. Peripheral blood-derived monocytes were obtained from each dog and then stimulated with PRR ligands for 6 and 24 hr; subsequently, messenger RNA (mRNA) expression levels and protein secretion of IL-1β were quantified using quantitative real-time PCR and ELISA, respectively. The levels of IL-1β mRNA and protein secretion after stimulation with a nucleotide-binding oligomerization domain 2 (NOD2) ligand were significantly greater in monocytes from ICRP-affected MDs than in those from control MDs. In addition, IL-1β protein secretion induced by toll-like receptor (TLR) 1/2, TLR2 and TLR2/6 stimulation was also significantly greater in ICRP-affected MDs. These results suggest that reactivity against NOD2, TLR1/2, TLR2 and TLR2/6 signals is enhanced in ICRP-affected MDs and may play a role in the pathogenesis of ICRPs in MDs. Additional studies of the genetic background of these PRRs should be performed.

著者

Mayumi NAKAJIMA Koichi OHNO Yuko GOTO-KOSHINO Yasuhito FUJINO Hajime TSUJIMOTO

出版者

公益社団法人 日本獣医学会

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.13-0583, (Released:2013-12-20)

被引用文献数

3 9

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Rapid turnover proteins such as transferrin (Tf) are used as dynamic nutritional assessment proteins in human medicine. However, nutritional status in veterinary medicine is mostly assessed on the basis of classical static factors such as body weight, body condition score and plasma albumin level. This study evaluated the clinical usefulness of Tf as nutritional assessment marker by measuring plasma Tf concentrations in malnourished dogs before and after nutritional treatment. Post plasma Tf concentrations were significantly higher than those of pre treatment, although albumin concentration did not change significantly. Numbers of dogs that exhibited increases in plasma Tf concentrations are significantly related to weight gain. Furthermore, the survival rates at day 60 after the treatment initiation were significantly higher in dogs with plasma Tf concentrations above the reference value (180 mg/dl) after the nutritional treatment than those with a plasma Tf concentration<180 mg/dl. In conclusion, plasma Tf concentration is related to nutritional condition and would be a candidate for novel nutritional assessment marker in dogs.

著者

Aki FUJIWARA-IGARASHI Yuko GOTO-KOSHINO Hiroyuki MOCHIZUKI Shingo MAEDA Yasuhito FUJINO Koichi OHNO Hajime TSUJIMOTO

出版者

公益社団法人 日本獣医学会

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

vol.75, no.6, pp.733-742, 2013 (Released:2013-07-01)

参考文献数

45

被引用文献数

6 11

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The p16, p15 and p14 genes are widely known as tumor suppressor genes in human medicine. Although a large number of genetic and epigenetic aberrations in these genes have been reported in human malignancies, canine malignancies have not been well analyzed on the aberrations of these genes. In this study, the full-length complementary DNA (cDNA) of the canine p16 gene was cloned using the 5’ and 3’ rapid amplification of cDNA ends methods. Based on the sequence data, primers specific for p16, p15 and p14 were designed. Using these primers, the expression of p16, p15 and p14 mRNAs could be individually evaluated by reverse transcriptase polymerase chain reaction. Genomic aberrations were also examined using genomic polymerase chain reaction. Two of the 6 canine lymphoid tumor cell lines did not express detectable levels of p16, p15 and p14 mRNAs, and wide-ranging deletions in the p15-p14-p16 genomic locus were suspected. Wide-ranging deletions were also speculated in 2 of 14 dogs with T-cell lymphoid tumors. On the other hand, similar failure of amplification suggesting wide-ranging deletions were not observed in any of the 14 dogs with B-cell lymphoma. Deletion of the p15-p14-p16 genomic locus could be one of the molecular aberrations in canine lymphoid tumor cells.

著者

Ko KOJIMA Yasuhito FUJINO Yuko GOTO-KOSHINO Koichi OHNO Hajime TSUJIMOTO

出版者

公益社団法人 日本獣医学会

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

vol.75, no.6, pp.727-731, 2013 (Released:2013-07-01)

参考文献数

21

被引用文献数

4 8

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Lymphoid malignancies, such as leukemia, and many types of lymphoma are common and severe disorders in dogs. Since shortening remission duration caused by resistance to chemotherapy often becomes clinically critical problems, development of novel and effective therapy should be required. The present study investigated the status of NF-κB and effect of its inhibitor, bortezomib, in six canine neoplastic lymphoid cell lines. NF-κB p65 and p50 were detected in the nuclear fraction of GL-1, CLBL-1 and CL-1, suggesting that NF-κB was constitutively activated in the cells. NF-κB p65 was detected in the cytoplasmic fraction of UL-1 and Ema. After incubation with bortezomib, NF-κB p50 and p65 became undetectable in the nuclear fraction of GL-1, CLBL-1 and CL-1, and CLBL-1, respectively, and p65 was clearly degraded in the cytoplasmic fraction of CLBL-1 and CL-1. Bortezomib inhibited the proliferation of all cell lines except Nody-1 in a concentration-dependent manner. The results indicated that constitutive activation of NF-κB could contribute to the proliferation of canine neoplastic lymphoid cells, and bortezomib would have suppressive effects on the NF-κB activation and the proliferation of neoplastic lymphoid cells in dogs.