A 12‐year‐old spayed female Dalmatian presented with acute vomiting and anorexia. The clinicopathological and imaging abnormalities included icterus, biliary obstruction, and multiple diffuse splenic ...hypoechogenic nodules. Cholecystectomy was performed to remove the obstruction, followed by liver biopsy and splenectomy. Histopathological and immunohistology evaluation of the spleen, liver, and gallbladder revealed splenic marginal zone lymphoma (MZL) with gallbladder and hepatic infiltration of neoplastic CD20/CD79α‐positive cells. Moreover, we observed clonal rearrangements of the immunoglobulin heavy‐chain (IgH) gene in all three tissues. The dog was in good condition without chemotherapy. However, there was progressive elevation of liver enzymes, which could be attributed to neoplastic hepatic infiltration. Chlorambucil and prednisolone were administered until day 108, when the liver enzyme levels normalized. On day 156, the dog developed diffuse large B‐cell lymphoma (DLBCL) of the peripheral lymph nodes. Sequence analysis of the clonally rearranged IgH gene revealed that all neoplastic cells in the spleen, gallbladder, and liver at initial presentation, as well as lymph nodes on day 156, possessed the same sequence identity of the amplified IgH fragments. This demonstrated that all neoplastic cells were derived from the same B‐lymphocyte clone. The DLBCL was considered to have transformed from the splenic MZL, with gallbladder involvement. In cases of splenic MZL, it is important to consider gallbladder involvement and transformation to DLBCL. Moreover, gallbladder lymphoma should be included in the differential diagnosis of dogs with gallbladder abnormalities. Further studies are warranted to investigate the prognosis of splenic MZL.
Our previous study indicated that cytotoxicity of intraepithelial lymphocytes is a poor prognostic factor in feline intestinal T-cell lymphoma (FITL), but the effect of cytotoxic lymphocytes on ...mucosal epithelium is still unknown. Thus, we investigated the association between cytotoxic lymphocytes and mucosal epithelium in 71 cases of feline intestinal T-cell lymphoma (FITL): epithelial injury, basement membrane injury, cleaved-caspase-3 positivity of epithelial cells, and the number and Ki67 positivity of intraepithelial lymphocytes in granzyme B (GRB)+ and GRB- FITLs were evaluated. Epithelial injury score and the number of intraepithelial lymphocytes in granzyme B (GRB)+ FITL were significantly higher than those of GRB- FITL (P<0.05, P<0.05), but no significant differences were found in the basement membrane injury score, the percentage of cleaved-caspase-3+ epithelial cells, and the percentage of Ki67+ intraepithelial lymphocytes. There was a significant correlation between the epithelial injury score and the number of intraepithelial lymphocytes (P<0.05), but no significant correlation was observed between the epithelial injury score and Ki67+ percentage of intraepithelial lymphocytes. Because epithelial cell cleaved-caspase-3 positivity was observed in FITL, regardless of GRB expression in lymphocytes, GRB-mediated apoptosis may not contribute to epithelial injury in FITL. The association between increased number of intraepithelial lymphocytes and epithelial injury suggests that intraepithelial lymphocytes infiltration may contribute to epithelial injury in FITL.
The novel domestic cat hepadnavirus (DCH), a member of the Hepadnaviridae, was first detected in Australia and has recently been identified in more countries. In this study, we explored the DCH ...genome using next-generation sequencing of a plasma sample from a cat with a fever of unknown cause. Nucleotide sequence analysis showed the virus to be relatively genetically distant from the first reported DCH in Australia, showing 89% homology. Then we conducted an epidemiological survey by PCR of plasma samples collected from 203 cats that visited a veterinary hospital for diagnosis and treatment. Two of the 203 surveyed cats a were positive for DCH. One of the two positive cases had elevated liver enzymes of unknown etiology, and the other had hepatocellular adenoma. Our study indicated that DCH infection was observed in domestic cats in the Tokyo area of Japan as well as other reported areas in the world. Further investigations are needed to define the clinical importance of DCH.
Intestinal lymphangiectasia (IL) is a common complication in dogs. This study analyzed intestinal microbiota using 16S rRNA amplicon analysis as candidate factors that strongly influence the small ...intestinal lymphatic vessels in dogs with and without IL. Twelve dogs were included, of which six were diagnosed with lymphoplasmacytic enteritis, four with small-cell lymphoma, and two with large-cell lymphoma. Seven of these dogs had IL, whereas five did not. First, the microbial diversity analyzed by Faith pd index was significantly decreased in dogs with IL compared to dogs without IL. Then, the relative amounts of each bacterial taxa were compared between dogs with and without IL using Linear discriminant analysis effect size analysis. At the genus level, the Ruminococcus gnavus group significantly increased in dogs with IL compared to dogs without IL. A total of four genera, including Ruminococcus torques group and Faecalibacterium, which produce butyrate, significantly decreased in dogs with IL. This study showed decreased intestinal bacterial diversity and several alterations of intestinal microbiota, including a decrease in butyrate-producing bacteria in dogs with IL, compared to dogs without IL.
A 9‐month‐old intact crossbred female cat was presented with jaundice, intermittent anorexia and lethargy, increased hepatic enzyme activities, and hyperammonemia. Abdominal ultrasound and computed ...tomographic examinations determined that the liver had a rounded and irregular margin, and histopathological examination identified excessive accumulation of copper hepatocytes in the liver. Concentrations of both blood and urine copper were higher than in healthy cats. The patient responded well to treatment with penicillamine. Clinicopathological abnormalities and clinical signs improved within 2 months, and the patient was alive for >9 months after starting treatment. Genetic examination determined that the patient and its littermate had a single‐nucleotide variation (SNV, p. T1297R) that impaired the function of the ATP7B gene product; the gene that is mutated in patients with Wilson's disease (WD). Hepatic copper accumulation was believed to be associated with the SNV of the ATP7B gene, and the patient had a genetic disorder of copper metabolism equivalent to WD in humans.
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.
Interactions between tumor and immune cells within the tumor microenvironment play an important role in tumor progression, and small extracellular vesicles (EVs) derived from these tumor cells have ...been shown to exert immunomodulatory effects on various immune cells, including macrophages and lymphocytes. Although the immunomodulatory effects of small EVs derived from human cancer cells have been intensively investigated, few studies have investigated the effects of lymphoma-derived small EVs on macrophages in both human and veterinary medicine. Here, we evaluated the effects of canine lymphoma-derived small EVs on canine primary monocytes, which are the major source of macrophages in neoplastic tissues. Comprehensive gene expression analysis of these treated monocytes revealed their distinct activation via the Toll-like receptor (TLR) and NF-κβ signaling pathways. In addition, treatment with lymphoma small EVs increased the secretion of MCP-1, which induces the infiltration and migration of monocytes and lymphocytes in neoplastic and cancer tissues. The results of this study indicate that canine lymphoma small EVs activate monocytes, possibly through the activation of TLR and NF-κβ signaling pathways, and induce monocytes to secrete of MCP-1, which might contribute to immune cell infiltration within the tumor microenvironment.
A 12‐year‐old castrated male mixed breed dog was presented with anorexia, lethargy, intermittent vomiting, diarrhea, and weight loss. Clinicopathologic and imaging abnormalities included ...pancytopenia, icterus, and splenomegaly with multiple minute hypoechogenic nodules. Bone marrow (BM) smears revealed 2.5% hemophagocytic macrophages. In addition, an increased number of small to intermediate lymphocytes (16.3%) and plasma cells (3.2%) were recognized in the BM smears. More than 80% of the lymphocytes contained multiple small intracytoplasmic magenta granules. Histopathologic findings of the spleen revealed hemophagocytosis. Large granular lymphocytes (LGLs) were not found on the liver cytology or splenic histopathology at this time. PCR for antigen receptor rearrangement (PARR) analysis showed a clonal reaction in the T‐cell receptor ɤ (TCRɤ) gene in the BM sample. The dog was diagnosed with hemophagocytic syndrome (HPS). The dog was maintained in good condition with immunosuppressive therapy. However, the dog developed hepatic LGL lymphoma 7 months later. At this time, PARR analysis showed a clonal TCRɤ gene rearrangement in the hepatic LGL lymphoma samples. The BM and liver sample clonal rearrangements showed 100% homology, indicating that the small to intermediate granular lymphocytes in the BM at the HPS stage had progressed to hepatic LGL lymphoma. To our knowledge, this is the first report of canine secondary HPS caused by the occurrence of a BM LGL lymphoma clone that progressed to hepatic LGL lymphoma.
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.
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.
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