A canine case of Ehrlichia canis infection without a history of being in an endemic area in Japan.

A mixed-breed, 8-year-old male dog developed neutropenia, thrombocytopenia, and hyperglobulinemia. Bone marrow hyperplasia and splenic plasmacytosis were cytologically observed. The dog had never been outside of Tokyo or Shizuoka Prefecture. Splenectomy was performed to confirm and remove the cause of splenic plasmacytosis. A histopathological diagnosis of splenic plasmacytoma was made; however, serum protein electrophoresis showed polyclonal gammopathy. Further screening was performed, and Ehrlichia canis infection was confirmed. The dog was treated with doxycycline for 5 weeks. After the antibiotic therapy, no relapse of neutropenia, thrombocytopenia, hyperglobulinemia, or positive polymerase chain reaction result of E. canis infection was observed for 3 years. Careful attention should be given to ehrlichiosis when exploring the cause of pancytopenia or hyperglobulinemia, regardless of the travel history.

Gene expression profiles associated with early relapse during first remission induction in canine multicentric high-grade B-cell lymphoma.

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.

Intraepithelial lymphocytes are associated with epithelial injury in feline intestinal T-cell lymphoma.

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.

Detection of feline morbillivirus in cats with symptoms of acute febrile infection.

Feline morbillivirus (FeMV) was identified for the first time in cats in 2012 in Hong Kong. Although its association with chronic kidney disease in cats has attracted the attention of researchers, its clinical significance as an acute infection has not been reported. Previously, we reported FeMV detection using next-generation sequence-based comprehensive genomic analysis of plasma samples from cats with suspected acute febrile infections. Here, we conducted an epidemiological survey to detect FeMV by quantitative reverse transcription polymerase chain reaction (qRT-PCR) using blood samples from cats in Japan. FeMV was detected in 32/102 blood samples (31.4%) from cats with suspected acute viral infections. Most of the FeMV-positive cats had clinical findings consistent with acute viral infections, including fever, leukopenia, thrombocytopenia and jaundice. No FeMV was detected in healthy cats or clinically ill cats that visited veterinary hospitals. Phylogenetic analysis classified FeMV L genes into various FeMV subtypes. We also necropsied a FeMV-positive cat that died of a suspected acute infection. On necropsy, FeMV was detected in systemic organs, including the kidneys, lymph nodes and spleen by qRT-PCR and immunohistochemical staining. These results suggest that FeMV infections may cause acute symptomatic febrile infections in cats. A limitation of this study was that the involvement of other pathogens that cause febrile illnesses could not be ruled out and this prevented a definitive conclusion that FeMV causes febrile disease in infected cats. Further studies that include experimental infections are warranted to determine the pathogenicity of FeMV in cats.

Application of automated machine learning for histological evaluation of feline endoscopic samples.

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.

MUC5AC and MUC5B expression in canine gallbladder mucocele epithelial cells.

Gallbladder mucocele (GBM) is one of the most common gallbladder diseases in dogs. Its pathogenesis has not yet been clarified, but excessive accumulation of a secretory gel-forming mucin, MUC5AC in the gallbladder has been reported. This study aimed to ascertain if MUC5AC overproduction resulted in mucus accumulation in the gallbladder during GBM development. Eleven dogs undergoing cholecystectomy who were pathologically diagnosed with GBM were included, and the expression level of mucins, particularly MUC5AC and MUC5B, in their gallbladder epithelial cells was compared with those in normal gallbladder epithelial cells. On reverse transcription-quantitative polymerase chain reaction screening, there was a significant difference (P<0.05) in the mRNA expression level of MUC1, but not of other mucins including MUC5AC and MUC5B, between mucocele and normal gallbladder epithelial cells. Protein expression levels were also evaluated for MUC5AC and MUC5B using immunohistochemistry. There was little immunoreactivity for MUC5AC, whereas MUC5B showed definitive staining in gallbladder epithelial cells. There was no difference in MUC5AC and MUC5B protein expression levels between mucocele and normal gallbladder epithelial cells. These data suggest that excessive production of mucin, especially MUC5AC and MUC5B, does not occur in canine GBM, and that abnormal mucus excretion, rather than excessive mucus production, may be the cause of GBM development.

Diagnosis, management and genetic analysis of a cat with primary copper hepatopathy.

Case summary: A 2-year-old spayed female domestic longhair cat was presented for evaluation of chronic ocular discharge and occasional vomiting. While physical examination findings were consistent with an upper respiratory infection (URI), serum chemistry results revealed increased liver enzyme activities. Histopathologic examination of a liver biopsy identified substantial centrilobular accumulation of copper in hepatocytes - strongly suggestive of primary copper hepatopathy (PCH). Retrospective cytologic examination of a liver aspirate also identified copper aggregates in hepatocytes. After transitioning to a low-copper diet, 1 year of chelation therapy with D-penicillamine achieved normalization of liver enzyme activities and resolution of persistent ocular signs. Subsequently, a long-term regimen of zinc gluconate has been successfully managing the cat's PCH for almost 3 years. Sanger sequencing of the cat's ATP7B gene, which encodes a copper-transporting protein, revealed a novel, 'likely pathogenic', single nucleotide variation (c.3670t/a [p.Trp1224Arg]), for which the cat is heterozygous. Relevance and novel information: Recommendations are described for the long-term clinical management of feline PCH - a previously attainable but unreported outcome - with considerations for mitigating the speculated oxidation-exacerbated ocular risks of concurrent URI. This report is the first to include identification of copper aggregates in a liver aspirate from a cat - evidence that liver aspirates from cats could be routinely examined for copper as is standard practice for those from dogs. The cat is also the first reported with PCH and a 'likely pathogenic' heterozygous ATP7B genotype, which suggests that normal ATP7B alleles could be recessive to or incompletely/co- dominant with deleterious ATP7B alleles in cats, as has been reported in other species.

Detection of domestic cat hepadnavirus by next-generation sequencing and epidemiological survey in Japan.

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.

Whole exome and transcriptome analysis revealed the activation of ERK and Akt signaling pathway in canine histiocytic sarcoma.

Histiocytic sarcoma (HS) is an incurable aggressive tumor, and no consensus has been made on the treatment due to its rare occurrence. Since dogs spontaneously develop the disease and several cell lines are available, they have been advocated as translational animal models. In the present study, therefore, we explored gene mutations and aberrant molecular pathways in canine HS by next generation sequencing to identify molecular targets for treatment. Whole exome sequencing and RNA-sequencing revealed gene mutations related to receptor tyrosine kinase pathways and activation of ERK1/2, PI3K-AKT, and STAT3 pathways. Analysis by quantitative PCR and immunohistochemistry revealed that fibroblast growth factor receptor 1 (FGFR1) is over-expressed. Moreover, activation of ERK and Akt signaling were confirmed in all HS cell lines, and FGFR1 inhibitors showed dose-dependent growth inhibitory effects in two of the twelve canine HS cell lines. The findings obtained in the present study indicated that ERK and Akt signaling were activated in canine HS and drugs targeting FGFR1 might be effective in part of the cases. The present study provides translational evidence that leads to establishment of novel therapeutic strategies targeting ERK and Akt signaling in HS patients.

Analysis of fecal microbial profiles in dogs with intestinal lymphangiectasia.

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.

Clinical characteristics and outcomes of Mott cell lymphoma in nine miniature dachshunds.

BACKGROUND: Lymphoma with Mott cell change, or Mott cell lymphoma (MCL), is an uncommon variant of canine lymphoma. Because of its rare occurrence, there has been no comprehensive study describing the disease so far. Miniature dachshunds, a popular breed in Japan, sometimes experience MCL. OBJECTIVES: To investigate the clinical characteristics and outcomes of MCL in miniature dachshunds. METHODS: Medical records were retrospectively reviewed to identify miniature dachshunds diagnosed with MCL and other types of lymphoma. Data on clinical and laboratory findings, treatments and outcomes were collected. Survival times were compared between miniature dachshunds with MCL and other types of lymphoma. RESULTS: Of the 87 miniature dachshunds diagnosed with lymphoma, 9 (10%) had cytological characteristics of MCL. All 9 miniature dachshunds with MCL were categorised as having alimentary lymphoma (small and/or large intestine, 6 dogs; mesenteric lymph node, 3 dogs). The median age was 3.1 years (range, 2.0-9.4 years). All nine dogs were treated with chemotherapeutic protocols used for large cell lymphoma or alkylating agents such as melphalan or chlorambucil. The overall response rate to initial chemotherapy was 78%, and the median progression-free survival was 105 days. Overall survival in these nine dogs ranged from 6 to >1513 days (median, 240 days), which was significantly longer than in 29 miniature dachshunds with alimentary large cell lymphoma other than MCL (median, 57 days; p = 0.0491). CONCLUSIONS: MCL in miniature dachshunds can be recognised as a peculiar type of B-cell lymphoma occurring in relatively young dogs as an alimentary form and has a longer survival compared with typical alimentary large cell lymphoma.

Effects of proportions of carbohydrates and fats in diets on mucin concentration and bile composition in gallbladder of dogs.

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.

Intraepithelial cytotoxic lymphocytes are associated with a poor prognosis in feline intestinal T-cell lymphoma.

The expression of cytotoxic molecules in feline intestinal T-cell lymphoma cells was examined immunohistochemically using endoscopic samples of 50 cases. Cases included 14 large-cell lymphomas (LCLs) and 36 small-cell lymphomas (SCLs). Most LCL and some SCL exhibited marked erosion and villous atrophy. Clonal T-cell receptor (TCR) gene rearrangement was detected in 10/14 (71%) LCL cases and 33/36 (92%) SCL cases. No clonal immunoglobulin heavy chain (IgH) gene rearrangement was detected. Immunohistochemically, all cases were positive for CD3 and negative for CD79α, CD30, CD56, and Foxp3. LCLs were positive for CD8 in 13/14 cases (93%), T-cell intracellular antigen 1 (TIA1) in 14/14 cases (100%), and granzyme B in 6/14 cases (43%). SCLs were positive for CD8 in 28/36 cases (78%), TIA1 in 33/36 cases (92%), and granzyme B in 2/36 cases (6%). TIA1- and granzyme B-positive neoplastic lymphocytes were predominantly observed in the mucosal epithelium of 10/50 cases (20%) and 6/50 cases (12%), respectively. No significant differences in survival time were found based on cell size or epitheliotropism. However, cases with TIA1+ and/or granzyme B+ neoplastic lymphocytes predominantly in the mucosal epithelium had significantly shorter survival times (P < .05), suggesting that mucosal epithelium infiltration of neoplastic cells with a cytotoxic immunophenotype is a negative prognostic factor. Therefore, intraepithelial cytotoxic lymphocytes may be associated with mucosal injury and impaired intestinal function, leading to a poor prognosis in cats with intestinal T-cell lymphoma.

Changes in gene expression profiles and cytokine secretions in peripheral monocytes by treatment with small extracellular vesicles derived from a canine lymphoma cell line.

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-κß 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-κß signaling pathways, and induce monocytes to secrete of MCP-1, which might contribute to immune cell infiltration within the tumor microenvironment.

Evaluation of the degree and distribution of lymphangiectasia in full-thickness canine small intestinal specimens diagnosed with lymphoplasmacytic enteritis and granulomatous lymphangitis.

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.

Anti-CCR4 treatment depletes regulatory T cells and leads to clinical activity in a canine model of advanced prostate cancer.

BACKGROUND: Targeting regulatory T cell (Treg) infiltration is an emerging strategy for cancer immunotherapy. However, its efficacy in advanced prostate cancer remains unclear. Here, we showed the therapeutic efficacy of anti-Treg treatment in a canine model of advanced prostate cancer. METHODS: We used dogs with naturally occurring prostate cancer to study the molecular mechanism underlying Treg infiltration and the effect of anti-Treg treatment. Tumor-infiltrating Tregs was evaluated by immunohistochemistry, and the association with prognosis was examined in dogs with spontaneous prostate cancer. The molecular mechanism of Treg infiltration was explored by RNA sequencing and protein analyses. A non-randomized canine clinical trial was conducted to define the therapeutic potential of anti-Treg treatment for advanced prostate cancer. Human prostate cancer datasets were analyzed to compare gene expression in dogs and humans. RESULTS: Tumor-infiltrating Tregs were associated with poor prognosis in dogs bearing spontaneous prostate cancer. RNA sequencing and protein analyses showed a possible link between the CCL17-CCR4 pathway and the increase of tumor-infiltrating Tregs. Dogs with advanced prostate cancer responded to mogamulizumab, a monoclonal antibody targeting CCR4, with decreased circulating Tregs, improved survival, and low incidence of clinically relevant adverse events. Urinary CCL17 concentration and BRAFV595E mutation were independently predictive of the response to mogamulizumab. Analysis of a transcriptomic dataset of human prostate cancer showed that the CCL17-CCR4 axis correlated with Foxp3. In silico survival analyses revealed that high expression of CCL17 was associated with poor prognosis. Immunohistochemistry confirmed that tumor-infiltrating Tregs expressed CCR4 in human patients with prostate cancer. CONCLUSIONS: Anti-Treg treatment, through CCR4 blockade, may be a promising therapeutic approach for advanced prostate cancer in dogs and some population of human patients.

Outcomes and prognostic factors in canine epitheliotropic and nonepitheliotropic cutaneous T-cell lymphomas.

Canine cutaneous lymphoma is an uncommon lymphoma in dogs. Most canine cutaneous lymphoma cases have a T-cell origin. Canine cutaneous T-cell lymphoma (CTCL) is classified into epitheliotropic and nonepitheliotropic cutaneous lymphomas, and each type of lymphoma is subclassified into several histological subtypes. Limited information is available regarding the prognostic significance of clinical variables and histopathological subtypes in dogs with CTCL. This retrospective study aimed to investigate the influence of clinical variables and histopathological subtypes on the prognosis of dogs with CTCL. Forty-six dogs diagnosed with CTCL by histopathological examination were included. Histopathological specimens were reexamined and classified into CTCL subtypes. The influence of the type of skin lesion, histopathological subtype, haematological examination results and treatment response on the overall survival time (OS) was examined. Thirty-one dogs were diagnosed with epitheliotropic CTCL (mycosis fungoides in 28 dogs; pagetoid reticulosis in 3 dogs) and 15 dogs were diagnosed with nonepitheliotropic CTCL (anaplastic large T-cell lymphoma in 6 dogs; peripheral T-cell lymphoma, not otherwise specified, in 9 dogs). The OS of dogs diagnosed with epitheliotropic CTCL (141 days) was significantly shorter than that of dogs diagnosed with nonepitheliotropic CTCL (374 days). As clinical variables, the presence of neoplastic lymphocytes in peripheral blood, thrombocytopenia and initial chemotherapeutic response was related to prognosis. Our results demonstrated that histopathological subtype and several clinical variables were found to influence the prognosis of dogs with CTCL.

Efficacy and adverse events of continuous l-asparaginase administration for canine large cell lymphoma of presumed gastrointestinal origin.

We examined the efficacy and adverse events of continuous l-asparaginase administration in dogs with large cell lymphoma of presumedgastrointestinal (GI) origin. We retrospectively reviewed medical records of dogs with large cell lymphoma of presumed GI origin treated with continuous l-asparaginase administration from 2009 to 2018. We collected information on the signalment, lesion site, complete blood count, serum biochemical profile, diagnostic imaging findings, cytological and histopathological findings, immunophenotype, l-asparaginase administration frequency, treatment response, adverse events, rescue protocol, and patient outcomes. Clinical outcomes were assessed using medical records or by contacting the owner or referring veterinarian. Thirty-two dogs with large cell lymphoma of presumed GI origin received weekly l-asparaginase administration. The median number of l-asparaginase injections was seven (range: 1-30). Although two of the 32 dogs had GI toxicity of grade 3 or higher, none developed a hypersensitivity reaction. The response rate based on ultrasonographic findings was 18/32 (56%) and that based on clinical signs was 30/32 (94%). The median overall progression-free survival was 50 days (range: 2-214 days), and median overall survival was 147 days (range: 2-482 days). Adverse events associated with continuous l-asparaginase administration were rare. Clinical signs at diagnosis improved in most cases. Based on these results, continuous l-asparaginase administration appears to be a reasonable treatment option for dogs with large cell lymphoma of presumed GI origin.

Association between intestinal lymphangiectasia and expression of inducible nitric oxide synthase in dogs with lymphoplasmacytic enteritis.

Intestinal lymphangiectasia (IL) is a common complication in dogs. Since nitric oxide (NO) is known to relax the lymphatic vessel, 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.