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C-C chemokine receptor 7 (CCR7) contributes to cell homing to lymph nodes (LNs). Recent studies reported that CCR7 is also expressed in tumor cells, which correlates with LN metastasis in various cancers. However, the expression of CCR7 in tumor cells is unknown in dogs due to the lack of appropriate antibodies. In the present study, a fusion protein of C-C chemokine ligand 19 (CCL19) was employed as an alternative method to CCR7 antibodies. The fusion CCL19 protein specifically detected CCR7 expressed in canine lymphoma cell lines, which showed active chemotaxis to both canine and mouse ligands. The present study will help further research on the involvement of canine CCR7 in LN metastasis. more...

Canine degenerative myelopathy (DM) is a progressive neurodegenerative disease of the spinal cord. The diagnosis is based on the observation of clinical signs, genetic testing, and exclusion of other spinal cord diseases, and a definitive diagnosis of DM can only be confirmed by postmortem histopathological findings. The aim of this study was to investigate the diagnostic ability of diffusion tensor imaging (DTI) for DM. Eight DM-affected Pembroke Welsh Corgis, thirteen dogs with thoracolumbar intervertebral disk herniation (IVDH), and six healthy control dogs were included. All dogs were scanned using a 3.0-T MRI system. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values were calculated for each intervertebral disk level slice between T8-T9 and L2-L3 intervertebral disk levels, and the entire area of the thoracolumbar spinal cord between T8-T9 and L2-L3 intervertebral disk levels (T8-L3 region). The ADC and FA values of the T8-L3 region were significantly lower in the DM group than in the IVDH group. The ADC values for the T8-L3 region had a moderate negative correlation with clinical duration (r more...

In human erythema multiforme (EM), cytotoxic T lymphocytes (CTLs) play an essential role in the pathogenesis. In canine EM, immunohistochemical staining with anti-CD8 antibody using frozen sections has shown the involvement of CTLs; however, CTL infiltration has never been quantitatively analyzed. We herein quantitatively analyzed CTL infiltration by immunohistochemical staining with granzyme B and CD3 antibodies using paraffin sections of a dog with EM associated with zonisamide. The present results indicated approximately 70% of cells at the border between the epidermis and dermis consisted of CTLs. Detection of granzyme B and CD3 using paraffin sections employed in this study can be a clinically applicable method for detecting CTLs. more...

A 17-year-old mongrel dog and 12-year-old Shiba Inu dog presented with ataxia and paresis of the pelvic limbs, respectively. Gas accumulation within the spinal canal adjacent to the herniated disc was suspected in both cases. Since the gas remained accumulated for a prolonged period, hemilaminectomy was performed to decompress the spinal cord. The bulged external lamina of the dura matter was removed and histopathologically examined. Granulomatous inflammation and hyperplasia of fibrous connective tissues was noted, suggesting that the gas was encapsulated and the fibrous nodules made reabsorption difficult. Clinical signs resolved post-surgery. This is the first report describing histopathological features of pneumorrhachis in dogs. The accumulated gas was successfully removed by surgery. Postoperative course remained uneventful in both cases. more...

OBJECTIVE To measure expression of microRNAs (miRNAs) in plasma and in extracellular vesicles (EVs) derived from plasma for dogs with glioma and dogs with other brain diseases. SAMPLE Plasma samples from 11 dogs with glioma and 19 control dogs with various other brain diseases. PROCEDURES EVs were isolated from plasma samples by means of ultracentrifugation. Expression of 4 candidate reference miRNAs (let-7a, miR-16, miR-26a, and miR-103) and 4 candidate target miRNAs (miR-15b, miR-21, miR-155, and miR-342-3p) was quantified with reverse transcription PCR assays. Three software programs were used to select the most suitable reference miRNAs from among the 4 candidate reference miRNAs. Expression of the 4 target miRNAs was then calculated relative to expression of the reference genes in plasma and EVs, and relative expression was compared between dogs with glioma and control dogs with other brain diseases. RESULTS The most suitable reference miRNAs were miR-16 for plasma and let-7a for EVs. Relative expression of miR-15b in plasma and in EVs was significantly higher in dogs with glioma than in control dogs. Relative expression of miR-342-3p in EVs was significantly higher in dogs with glioma than in control dogs. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that miR-15b and miR-342-3p have potential as noninvasive biomarkers for differentiating glioma from other intracranial diseases in dogs. However, more extensive analysis of expression in specific glioma subtypes and grades, compared with expression in more defined control populations, will be necessary to assess their clinical relevance. more...

Degenerative myelopathy (DM) is an adult-onset, progressive neurological disease affecting several breeds of dog. Homozygosity or compound heterozygosity for the canine superoxide dismutase 1 (SOD1) gene mutations, possibly modulated by the modifier SP110 locus, are associated with a high risk for DM. Although the pathophysiological mechanisms are largely unknown, a role for mutant SOD1 in causing neuronal degeneration has been postulated. Three Hovawart dogs, 9e12 years of age, developed slowly progressive incoordination and weakness of the pelvic limbs leading to non-ambulatory flaccid paraparesis and muscle atrophy. Neuropathological lesions comprised axonal degeneration and loss of ascending and descending spinal pathways, which were most severe in the mid- to caudal thoracic segments. Accumulation of mutant SOD1 protein in neurons and reactive astrocytes was demonstrated by immunolabelling with the 16G9 antibody against the mutant SOD1 protein (p.E40K amino acid substitution). All three dogs were homozygous for the c.118A allele, but none had the SP110 ‘risk’ haplotype, suggesting a weak association of SP110 with the onset of DM in this breed. Our data suggest that the Hovawart breed is predisposed to the SOD1:c.118G>A mutation, which is associated with the development of DM. Prevention of DM could be achieved with the help of strategies based on epidemiological and genetic testing. more...

A 1-year- and 11-month-old spayed female toy poodle had showed progressive ataxia and paresis in the hindlimbs since 11 months old. Magnetic resonance imaging revealed high signal intensity on T2-weighted and fluid-attenuated inversion recovery images at the thoracic and lumbar spinal cord. The dog’s neurological condition slowly deteriorated and flaccid tetraparesis was exhibited. At 4 years and 11 months old, the dog died of respiratory failure. On postmortem examination, eosinophilic corkscrew bundles (Rosenthal fibers) were observed mainly in the thoracic and lumbar spinal cord. Histological features were comparable to previously reported cases with Alexander disease. This is a first case report to describe the clinical course and long-term prognosis of a dog with Alexander disease. more...

A 9-year-old neutered male Wire Fox Terrier presented with an 1-month history of hindlimb paresis. Magnetic resonance imaging revealed a contrast-enhanced mass at the level of the L2 vertebral canal. The dog became paraplegic with no deep perception of the hindlimbs, and the mass was surgically removed. The histopathological diagnosis was of a malignant peripheral nerve sheath tumor (MPNST). The dog suffered a relapse of right hindlimb ataxia at 225 days after the surgery. The dog died 434 days after the surgery. Necropsy found a large mass in the abdominal cavity invading from the L2-nerve. This is the first report of MPNST invading the abdominal cavity through the nerve root. more...

Thoracolumbar intervertebral disk herniation (TL-IVDH) with caudal articular process anomalies has been reported in Pugs. It currently remains unclear whether congenital caudal articular process aplasia/hypoplasia predisposes to the development of TL-IVDH. However, there are difficulties in proving the causal relationship between caudal articular process anomalies and TL-IVDH. The aim of this study was to describe the prevalence of TL-IVDH at the vertebral space containing anomalous and normal caudal articular processes in Pugs. Fifty-seven pugs were eligible to be included in this study. Caudal articular process aplasia/hypoplasia affected 52/57 (91.2%) dogs. The caudal articular process anomalies were most frequently located between T10 and T13. Colocalization of caudal articular process aplasia/hypoplasia and TL-IVDH was detected in 11 dogs (19.3%). The prevalence of TL-IVDH at vertebral spaces containing abnormal caudal articular processes was 12.3%, whereas the prevalence of TL-IVDH at vertebral spaces containing normal articular processes was 2.4%. With the increase in the number of vertebrae with caudal articular process anomalies, the prevalence of TL-IVDH also increased. The results of this study suggested the prevalence of caudal articular process anomalies was high in Pugs. The caudal articular process anomalies could be associated with TL-IVDH. A large cohort is needed to prove the causal relationship between caudal articular process anomalies and TL-IVDH. more...

Simple Summary Canine degenerative myelopathy (DM) is a chronic, progressive, and fatal neurodegenerative disease. Although degenerative changes in dogs with DM are observed not only in the spinal cord white matter but also the dorsal root ganglion (DRG) neurons, these changes are undetectable on conventional magnetic resonance imaging (MRI). Therefore, we investigated the ability of water-excitation MRI to visualize the DRG in dogs, and whether volumetry of DRG has a premortem diagnostic value for DM. Using water-excitation MRI, DRG could be depicted in all dogs. To normalize the volumes of DRG, body surface area was the most suitable denominator. The normalized DRG volume in dogs with DM was significantly lower than those in control dogs and dogs with intervertebral disc herniation. The results of this study revealed that widespread atrophy of DRG was likely to occur in DM. Moreover, volume reductions of DRG were observed in dogs with DM in both the early disease stage and late disease stage. Our research suggests that the DRG volume obtained by the water-excitation technique could be used as a clinical biomarker for DM. Abstract Canine degenerative myelopathy (DM) is a progressive and fatal neurodegenerative disease. However, a definitive diagnosis of DM can only be achieved by postmortem histopathological examination of the spinal cord. The purpose of this study was to investigate whether the volumetry of DRG using the ability of water-excitation magnetic resonance imaging (MRI) to visualize the DRG in dogs has premortem diagnostic value for DM. Eight dogs with DM, twenty-four dogs with intervertebral disc herniation (IVDH), and eight control dogs were scanned using a 3.0-tesla MRI system, and water-excitation images were obtained to visualize and measure the volume of DRG, normalized by body surface area. The normalized mean DRG volume between each spinal cord segment and mean volume of all DRG between T8 and L2 in the DM group was significantly lower than that in the control and the IVDH groups (P = 0.011, P = 0.002, respectively). There were no correlations within the normalized mean DRG volume between DM stage 1 and stage 4 (rs = 0.312, P = 0.128, respectively). In conclusion, DRG volumetry by the water-excitation MRI provides a non-invasive and quantitative assessment of neurodegeneration in DRG and may have diagnostic potential for DM. more...

A 4-year-old male Toy Poodle was presented with a history of status epilepticus. On presentation, neurological examination revealed a delay in postural reactions in the right pelvic limb. Magnetic resonance imaging showed a fluid-containing cystic lesion that compressed the mesencephalon, hippocampus, and amygdala. The cyst was surgically removed via left rostrotentorial craniotomy. The final diagnosis was an intracranial ectopic choroid plexus cyst. The patient has remained free of seizures for 18 months after surgery. This is the first case report of an intracranial ectopic choroid plexus cyst that was surgically removed in a dog. more...

An 8-year-old castrated male cat presented with acute ataxia and paresis in all four limbs. The cat also exhibited signs of autonomic nervous system impairment. Magnetic resonance imaging revealed swelling of the brachial plexuses bilaterally. Despite treatment, the cat died after 10 days of treatment. A postmortem examination revealed swollen radial nerves and cervical nerve roots in which infiltration of inflammatory cells was histologically confirmed. Additionally, lymphocytic infiltration was found around the blood vessels of the sciatic nerve bundle and the vagus nerve. Histological features were comparable to previously reported brachial plexus hypertrophic neuritis in a cat. Our case was unique in that the autonomic nerves were also involved in addition to the somatic nerves in all four limbs. more...

A 4-year-old, male Bernese mountain dog was evaluated for a 1-year history of right hemiparesis. Computed tomography revealed a large hypoattenuating mass severely deforming the C5 vertebral arch, invading the C6 spinal canal, and causing spinal cord compression. The signal characteristics of magnetic resonance imaging indicated a lesion composed of adipose tissue. The mass was removed via right hemilaminectomy, and histopathological examination confirmed it was an infiltrative lipoma. The compressive lesion remained unresolved, so the dog underwent a second operation, after which he regained some ambulatory function. Although postoperative adjunctive radiation therapy was performed, the dog died 201 days after the first operation. more...

OBJECTIVE To compare ultracentrifugation, precipitation, and membrane affinity chromatography methods for isolation of extracellular vesicles (EVs) from canine plasma samples and to identify suitable reference genes for incorporation into a quantitative reverse transcription PCR assay of microRNA expression in plasma EVs of healthy dogs. ANIMALS 6 healthy Beagles. PROCEDURES Plasma samples were obtained from each dog, and EVs were isolated from 0.3 mL of these samples via ultracentrifugation, precipitation, and membrane-affinity chromatographic methods. Nanoparticle tracking analysis was performed to determine the concentration and size distribution of EVs isolated by the ultracentrifugation method. Expression levels (cycle threshold values) of 4 microRNAs (let-7a, miR-16, miR-26a, and miR-103) were then compared by means of quantitative reverse transcription PCR assay. Three statistical programs were used to identify the microRNAs most suitable for use as reference genes. RESULTS Results indicated that ultracentrifugation was the most stable of all 3 methods for isolating microRNAs from 0.3 mL of plasma. Nanoparticle tracking revealed that EV samples obtained by the ultracentrifugation method contained a mean ± SD of approximately 1.59 × 1010 vesicles/mL ± 4.2 × 108 vesicles/mL. Of the 4 microRNAs in plasma EVs isolated by ultracentrifugation, miR-103 was the most stable. CONCLUSIONS AND CLINICAL RELEVANCE The ultracentrifugation method has potential as a stable method for isolating EVs from canine plasma samples with a high recovery rate, and miR-103 may provide the most stable reference gene for normalizing microRNA expression data pertaining to plasma EVs isolated by ultracentrifugation. more...

Canine degenerative myelopathy (DM) is an adult-onset, progressive neurodegenerative disease that occurs in multiple dog breeds. A DM-associated mutation of the canine superoxide dismutase 1 (SOD1) gene, designated as c.118G>A (p.E40K), has been implicated as one of pathogenetic determinants of the disease in many breeds, but it remains to be determined whether the c.118G>A mutation is responsible for development or progression of DM in Collies. Previously, a Rough Collie was diagnosed clinically and histopathologically as having DM in Japan, suggesting the possibility that the Collie breed may be predisposed to DM due to the high frequency of c.118G>A in Japan. In this study, accumulation and aggregate formation of SOD1 protein were retrospectively demonstrated in the spinal cord of the DM-affected dog by immunohistochemical analysis. Furthermore, a molecular epidemiological survey revealed a high carrier rate (27.6%) and mutant allele frequency (0.138) of c.118G>A in a population of Collies in Japan, suggesting that the Collie breed may be predisposed to DM associated with c.118G>A, and the prevention of DM in Collies in Japan should be addressed through epidemiological and genetic testing strategies. more...

Atlantoaxial instability (AAI)/subluxation commonly occurs in small breed dogs. Ventral stabilization techniques using screws and/or pins and a plate or, more commonly, polymethylmethacrylate are considered to provide the most favorable outcome. However, the implantation of screws of sufficient sizes for long-term stability becomes challenging in toy breed dogs (e.g. more...

Canine degenerative myelopathy (DM) is characterized by progressive degeneration of the spinal cord. Although atrophic changes in the intercostal muscles were previously reported in the late stage of DM in Pembroke Welsh Corgis (PWCs), changes in respiratory function have not yet been examined. In the present study, we performed an arterial blood gas analysis and measured respiratory movements over progressive disease stages to document changes in respiratory function in DM-affected PWCs. We found that respiratory dysfunction progressed during the later stages of DM and correlated with a change in respiratory movement to the abdominal breathing pattern. These results suggested that hypoventilation occurred due to dysfunctional changes in the intercostal muscles and resulted in hypoxemia in the later stages of DM. more...

Dysphagia induces aspiration and causes aspiration pneumonia. There is no treatment for dysphagia fundamentally. Haloperidol reportedly induces dysphagia. In the present study, we established a haloperidol-induced dysphagia model in guinea pigs, and evaluated the effects of ginger, kikyoto, and a mixture of ginger and kikyoto on swallowing. Swallowing ability was evaluated using behavioral tests, computed tomography (CT), and videofluoroscopic examination of swallowing. To investigate the effect of ginger and kikyoto on swallowing, ginger, kikyoto, or a mixture of ginger and kikyoto was administered orally to guinea pigs with haloperidol-induced dysphagia. Effects of these compounds were evaluated with behavioral tests. Chronic administration of haloperidol reduced the number of swallows, as evaluated by the behavioral test and videofluoroscopic examination of swallowing. In our model, these compounds improved swallowing dysfunction. Our results suggest that this model might be useful in revealing the pathogenesis of dysphagia and evaluating compounds that might improve swallowing. more...

A 7-year-old cat was referred with pelvic limb ataxia. Radiography and CT revealed bone resorption of the L1 vertebral arch, and myelography identified a compressive extradural lesion. The mass was surgically removed and histopathologically diagnosed as giant cell osteosarcoma. Three years later, the recurrent tumor resection and vertebral fixation were performed. Six months later, vertebrectomy was performed to radically excise the recurrent mass and a titanium spinal cage was placed. The cat is alive approximately 5 years after the first surgery. This case report describes vertebrectomy and vertebral body replacement as a radical treatment for feline vertebral osteosarcoma. more...

In humans, increased levels of GFAP in the CSF and blood have been reported with various neural diseases. However, there has been no study describing the usefulness of GFAP in the blood for disease of the spinal cord in dogs. The aim of this study was to describe the utility of GFAP in serum for a diagnosis of progressive myelomalacia. Fifty-six dogs with acute thoracolumbar IVDD diagnosed by computed tomography with myelography or MRI were included. Serum specimens were collected at initial presentation from all cases and at follow-up examinations from some cases. Serum samples were assayed for GFAP concentrations using a commercially available GFAP ELISA Kit. Progressive myelomalacia was the final diagnosis in 8/51 cases (15.6%). Eight dogs had clinical signs suggestive of progressive myelomalacia, of which 6 were positive and 2 were negative by GFAP. Seven dogs had a detectable level of serum GFAP, of which 6 had the onset of progressive myelomalacia. The sensitivity and specificity of the GFAP to progressive myelomalacia were 75% and 97.7%, respectively. The results suggest the utility of GFAP in serum in the diagnosis of progressive myelomalacia. more...

Canine degenerative myelopathy is an adult-onset, progressive neurodegenerative disease that occurs in multiple dog breeds, particularly Pembroke Welsh Corgis. Recently, a degenerative myelopathy-associated mutation of the canine SOD1 gene was identified as c.118G>A (p.E40K). In the present study, genotyping assays using conventional and real-time PCR methods were developed, and a preliminary genotyping survey was performed on 122 randomly selected Pembroke Welsh Corgis without any degenerative myelopathy-related clinical signs to determine the current allele frequency in Japan. Both of the assays provided clear-cut genotyping. The survey demonstrated the frequencies of the G/G wild-type, G/A heterozygote and A/A homozygote to be 9.0, 42.6 and 48.4%, respectively, indicating that the prevalence of the mutant A allele (69.7%) in Pembroke Welsh Corgis is extremely high in Japan. more...

Clarithromycin (CLM) has been known to increase the cyclosporine (CsA) trough levels in human transplant patients. However, the interaction of CLM with CsA has not been reported in cats. In this study, the effects of oral dosing of CLM on the pharmacokinetics and dosing of CsA in cats were investigated. Co-administration of CLM with CsA resulted in significant increases of oral bioavailability of CsA. In addition, CLM reduced the CsA dosage required to maintain the therapeutic CsA trough levels to almost 35% of the initial CsA therapy and the dose frequency was successfully replaced from a twice a day schedule to once a day in a feline kidney transplant patient. The addition of CLM to the regular CsA-based immunosuppression could be used as an effective alternative to classical ketoconazole treatment in feline kidney transplant patients and may result in substantial cost saving and convenience for the cat owners. more...

We report a cervical intraspinal cyst in a dog that was initially tetraparetic but spontaneously recovered completely. MRI revealed a well-demarcated intraspinal cyst located dorsally to a degenerated intervertebral disc. The location of the cyst and its signal features on MRI resembled those of discal cysts previously reported in humans. It has been reported in dogs that clinical signs of a intraspinal cyst are similar to those of intervertebral disc herniation and both conditions require surgical intervention. Unexpectedly, our case showed rapid spontaneous recovery and the follow-up MRI revealed complete resolution of the intraspinal cyst and spinal cord compression. Spontaneous recovery of degenerative intraspinal cyst may occur in dogs, similar to rare human cases as reported previously. more...

A 4-year-old neutered male Chihuahua was presented with a history of anorexia and vomiting. Continuous elevation of liver enzymes was found on repeated blood examinations and the dog was referred to us for further evaluation. The absence of gallbladder was suspected on ultrasonography. Exploratory laparotomy and retrograde cholangiography confirmed gallbladder agenesis and a possible hypoplasia of the right medial and lateral liver lobes. Histologically, proliferation of bile ductules associated with portal fibrosis and pseudolobular formation were apparent in the liver lobes. more...