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Transitional cell carcinoma ( TCC) is a urinary bladder tumour associated with high mortality in dogs. In this study, we investigated the feasibility of using p63, Ki67 or β-catenin as a clinical marker for predicting biological behaviour and prognosis in canine TCC. Expression levels of these proteins in TCC ( n = 25), polypoid cystitis ( n = 5) and normal urinary bladder ( n = 5) were scored after immunohistochemical staining. The staining scores for p63 ( P < 0.01) and β-catenin ( P < 0.05) in TCC were significantly lower than those in normal urinary bladder and polypoid cystitis. In contrast, Ki67 ( P < 0.01) staining scores in TCC were significantly higher than those in normal urinary bladder and polypoid cystitis. In TCC, low p63 expression was significantly related to the presence of vessel invasion ( P < 0.05) and metastasis ( P < 0.01) as well as short survival time ( P < 0.05). These findings show that p63 could be a reliable marker for predicting prognosis in canine TCC. [ABSTRACT FROM AUTHOR]

The article presents case study of a 57-year-old Japanese man presented with erythematous plaques and treated with phototherapy and topical maxacalcitol ointment. It offers information on Psoriasis which is a common inflammatory disorder characterized by well-demarcated hyperkeratotic erythema and plaques. It also mentions the topical application of vitamin D3 analogues which results in causing hypercalcaemia in humans.

We formulated a method to synthesize 1 kbp DNA fragments using 'oligomer unidirectional joining method' via asymmetric extension supported by a simulator for oligonucleotide extension (AESOE). In this study, trials were conducted on 41 sets of different genomic pieces of ten flaviviral genomes, and 31 bacterial 16s rRNA fragments with sizes ranging from 500 bases to 1.0 kbp. Synthetic gene production was found to be successful in all those sets. The synthesis method has three steps: the first step is a seven-linked AESOE, the second step is the linking of the 400-base fragments from the first step, and the third step is the final amplification. Our present approach is highly reproducible and may no longer require optimization of oligomer design.

This study investigated the association between caudal vena cava (CVC) size and circulatory dynamics in dogs using computed tomography (CT) under general anesthesia. The subjects were 104 dogs who had undergone CT under general anesthesia in the past. The ratio of short diameter of the CVC to aortic diameter (CVC S /Ao) and the ratio of long to short diameter of the CVC (CVC L /CVC S ) in the thorax and abdomen, respectively, were calculated using factors such as mean blood pressure (MBP), shock index (SI), anemia, hypoproteinemia, presence of intra-abdominal mass, and cardiac disease. There was a significant but negligible negative correlation between CVC S /Ao and MBP. In contrast, no significant correlation was found between CVC size and SI. The low MBP group had significantly higher CVC S /Ao of the thorax than the normal MBP group. The group with intra-abdominal mass had significantly lower CVC S /Ao of the abdomen than the group without intra-abdominal mass. The group with cardiac disease had significantly lower CVC L /CVC S of the thorax than the group without cardiac disease. In multiple regression analysis, low MBP, cardiac disease, intra-abdominal mass, and anemia were significant factors for CVC S /Ao of the thorax, CVC L /CVC S of the thorax, CVC S /Ao of the abdomen, and CVC L /CVC S of the abdomen, respectively. In conclusion, CVC size assessment using CT in dogs under general anesthesia is influenced by various factors.

Prostacyclin is an in vivo bioactive substance that regulates renal blood flow (RBF). Information regarding how epoprostenol, a prostacyclin preparation, affects RBF in dogs is lacking. We investigated the effects of short-term epoprostenol administration on RBF in six healthy dogs under anesthesia by administering it intravenously at human doses-2, 5, and 10 ng/kg/min for 20 min. RBF was evaluated before and during epoprostenol administration using pulsed Doppler ultrasonography, and renal perfusion was evaluated using contrast-enhanced ultrasonography. Effects on renal and systemic circulation were evaluated by measuring systolic arterial, mean arterial, diastolic arterial, pulmonary arterial, mean right atrial, and pulmonary capillary wedge pressures; heart rate; and cardiac output. Kruskal-Wallis and Bonferroni multiple comparison tests and Spearman's rank correlation coefficient were used for statistical analyses. As epoprostenol dosage increased, the peak systolic and end diastolic velocity of the renal artery, maximum and minimum venous flow velocities of the interlobular and renal veins, and heart rate all tended to increase, although not significantly. Our results indicate that human-dose epoprostenol administration in dogs does not cause significant changes in renal or systemic circulation. However, the human doses used may have been too low to produce a clinical effect in dogs.

Objective: Acidosis decreases myocardial contractile and myofibrillar responsiveness by reducing the calcium sensitivity of contractile proteins, which could reduce the effectiveness of pimobendan. We aimed to assess the cardiovascular effects of pimobendan in dogs subjected to acute respiratory acidosis., Design: Randomized crossover study with a 2-week washout period., Setting: University Laboratory., Animals: Six healthy research Beagle dogs., Interventions: Anesthetized dogs were administered 2 doses of IV pimobendan during conditions of eucapnia (Paco 2 35-40 mm Hg) and hypercapnia (Paco 2 90-110 mm Hg). Eucapnia was maintained by positive pressure ventilation and hypercapnia was induced by adding exogenous CO 2 to the anesthesia circuit. Heart rate (HR), systemic arterial blood pressure, cardiac output (CO), systemic and pulmonary vascular resistance (SVR and PVR, respectively), and pulmonary arterial pressure (PAP) were measured at baseline and 60 min after administering 0.125 mg/kg (low) and 0.25 mg/kg (high) pimobendan intravenously. Blood gas and biochemical analyses were performed at baseline and at the end of the experiment., Measurements and Main Results: The median baseline blood pH was 7.41 (range: 7.33-7.45) and 7.03 (range: 6.98-7.09) under conditions of eucapnia and hypercapnia, respectively. The serum concentrations of epinephrine and norepinephrine and the HR, CO, and PAP were higher, and SVR was lower at baseline in hypercapnic dogs. Pimobendan dose-dependently increased CO in eucapnia (baseline: 3.6 ± 0.2 L/kg/m 2 [mean ± SE], low: 5.0 ± 0.4 L/kg/m 2 , high: 5.8 ± 0.5 L/kg/m 2 , P < 0.001) and hypercapnia (baseline: 4.9 ± 0.5 L/kg/m 2 , low: 5.8 ± 0.5 L/kg/m 2 , high: 6.2 ± 0.5 L/kg/m 2 , P < 0.001), and increased HR and decreased SVR and PVR under both conditions (P < 0.001). In hypercapnia, the degree of increase or decrease of these cardiovascular measurements (except for PAP) by pimobendan was less than that in the eucapnic dogs., Conclusions: Pimobendan maintains function as an inodilator in anesthetized dogs with induced respiratory acidosis., (© Veterinary Emergency and Critical Care Society 2022.)

Objective: To identify the number of hepatic veins draining directly or indirectly into the caudal vena cava Thank you (CVC) using computed tomography angiography (CTA) in dogs., Study Design: Retrospective clinical study., Animals: Client-owned dogs (n = 77)., Methods: Abdominal CTA images were analyzed. Retrospective convenience sampling was performed using archived clinical cases to determine the number of hepatic veins in each liver lobe., Results: A median of 2 vessels from the right lateral lobe (range: 1-4) and the caudate process of the caudate lobe (range: 1-5) drained directly into the CVC. In the quadrate lobe, most common patterns consisted of 1 vessel directly draining to the CVC or indirectly via the left hepatic vein (LHV), and a vessel from quadrate lobe and right medial lobe merging into 1 vessel draining into the CVC or the LHV. A median of 3 vessels in the left lateral lobe (range: 2-8) and a median of 1 vessel in the left medial lobe (range: 1-3) drained into the LHV. In the papillary process of the caudate lobe, a median of 1 (range: 1-2) vessel drained directly into the CVC or the LHV., Conclusion: The draining pattern of hepatic veins varied widely in all liver lobes, especially the left lateral liver lobe., Clinical Significance: Veterinary surgeons should consider the potential presence of multiple hepatic veins and their draining pattern when performing hilar liver lobe resection. Attentive evaluation of a preoperative CTA is recommended for surgical planning., (© 2022 American College of Veterinary Surgeons.)

Background: Decreased p63 protein expression in canine transitional cell carcinoma (TCC) of the urinary bladder is associated with vascular invasion of the tumor, metastasis, and shortened survival. ΔNp63, an isoform of p63, is downregulated in high-grade invasive urothelial carcinoma in humans. However, the clinical significance of ΔNp63 expression in canine urinary bladder tumors is unknown. Therefore, it is essential to investigate ΔNp63 expression patterns in TCC, the most common urinary bladder tumor in dogs., Aim: This study aimed to evaluate the expression and role of ΔNp63 in canine TCC of the urinary bladder., Methods: ΔNp63 expression was compared between the normal canine urinary bladder, polypoid cystitis, and TCC. The correlation of ΔNp63 expression with histopathological and clinical findings were further evaluated, and its usefulness as a prognostic factor was examined., Results: We observed that ΔNp63 was highly expressed in dogs' normal urinary bladder and polypoid cystitis, and its expression levels were low in TCC. Furthermore, low levels of ΔNp63 expression were associated with vascular invasion, metastasis, and shortened survival in dogs with TCC., Conclusion: These results indicate that ΔNp63 expression could serve as a valuable biomarker for invasion, metastasis, and prognosis of canine TCC of the urinary bladder., Competing Interests: The authors declare that there are no conflicts of interest.

Gel pads are commonly used in skin ultrasonography; however, the effects of their thickness are unknown. This study investigated the effects of pad thickness on measurements of skin thickness in 10 beagle dogs. Sonograms to measure neck skin thickness were captured without pads and using pads with thicknesses of 3, 5, 10, and 20 mm. Without pads, acoustic shading was observed due to air bubbles in the coupling gel. With 20-mm pads, echogenic artifacts were observed on the skin surface. Entry echo with 20-mm pads was significantly higher than with 3-mm pads. This suggests that visibility of the skin structure could be affected when a gel pad is not used or when a thick gel pad is selected.

We have developed a novel method to predict the success of PCR amplification for a specific primer set and DNA template based on the relationship between the primer sequence and the template. To perform the prediction using a recurrent neural network, the usual double-stranded formation between the primer and template nucleotide sequences was herein expressed as a five-lettered word. The set of words (pseudo-sentences) was placed to indicate the success or failure of PCR targeted to learn recurrent neural network (RNN). After learning pseudo-sentences, RNN predicted PCR results from pseudo-sentences which were created by primer and template sequences with 70% accuracy. These results suggest that PCR results could be predicted using learned RNN and the trained RNN could be used as a replacement for preliminary PCR experimentation. This is the first report which utilized the application of neural network for primer design and prediction of PCR results.

We describe a 5-year-old castrated male dog suspected hypoglycemic encephalopathy that was evaluated by using diffusion-weighted imaging (DWI). The dog experienced hypoglycemia after prolonged generalized and continued partial seizures. In the acute phase, DWI showed hyperintensity in the left temporal lobe. After about a month, DWI maintained hyperintensity, and left middle cerebral artery dilation was noted on magnetic resonance angiography (MRA). In the chronic phase, the left temporal lobe lesion was replaced by cerebrospinal fluid. In humans, it was reported that cortical laminar necrosis (CLN) with hypoglycemic encephalopathy presents hyperintensity in the cerebral cortex on DWI and increased vascularity of the middle cerebral artery branches on MRA. In conclusion, DWI has detected CLN in a dog suspected hypoglycemic encephalopathy.

Increased intracranial pressure (ICP) can cause irreversible pathological changes in the canine brain and can be life-threatening, so prompt diagnosis and therapeutic responses are warranted. The purposes of this prospective experimental study were to evaluate phase-contrast MRI (PC-MRI) as a non-invasive method for quantifying cerebrospinal fluid (CSF) and basilar artery flow, and to assess effects of intravenous administration of hypertonic fluid. A PC-MRI scan was acquired for six healthy Beagle dogs at the level of the mesencephalic aqueduct. Either 1.0 g/kg mannitol or isotonic saline solution was administered intravenously for 15 min each at a matched dose volume of 5 mL/kg. Basilar artery and CSF flow rates were measured and their values compared between mannitol and isotonic saline solution groups before administration, and subsequently every 15 min for 2 h post-administration. The CSF dynamics were further assessed by measuring repeat flow from the caudal to rostral direction and the rostral to caudal direction as the number of waves. No significant difference was observed in basilar or and CSF flow velocity between the two groups (P > .05). However, administration of isotonic saline solution tended to increase basilar artery velocity slightly over time, while CSF velocity remained unchanged. In the mannitol group, CSF wave forms tended to be reduced at 60 and 75 min (P > .05). Findings from this preliminary study indicated that it is feasible to measure the dynamics of CSF and basilar artery flow by PC-MRI, but no flow differences could be detected for mannitol versus isotonic saline administration., (© 2020 American College of Veterinary Radiology.)

In humans, contrast-enhanced CT (CECT) has been used to indirectly assess the antiangiogenic effects demonstrated by a number of tyrosine kinase inhibitors. This retrospective, cross-sectional study aimed to quantitatively evaluate changes in tumor contrast-enhancement (CE) using CECT in solid tumor-bearing dogs treated with toceranib phosphate (TOC). The changes in tumor size and CE were measured using the Hounsfield unit (HU) scale in CECT images before TOC treatment and between 30 and 90 days after initiating the treatment. Among the 36 dogs treated with TOC, eight (22.2%) showed a partial response, 22 (61.1%) showed stable disease, and six (16.7%) showed progressive disease. Thirty (83.3%) of 36 dogs showed a decrease in tumor CE (median: -20%, range: -1% to -48%) after initiating the treatment. The results indicated that tumor CE and size changes were observed in tumor-bearing dogs that were treated with TOC; however, tumor CE was not significantly correlated with tumor regression. We suggest that these results could serve as pilot data to evaluate the antiangiogenic effects associated with TOC., (© 2020 American College of Veterinary Radiology.)

Thus far, there are few computed tomography (CT) characteristics that can distinguish benign and malignant etiologies. The criteria are complex, subjective, and difficult to use in clinical applications due to the high level of experience needed. This study aimed to identify practical CT variables and their clinical relevance for broadly classifying histopathological diagnoses as benign or malignant. In this prospective study, all dogs with liver nodules or masses that underwent CT examination and subsequent histopathological diagnosis were included. Signalments, CT findings and histopathological diagnoses were recorded. Seventy liver nodules or masses in 57 dogs were diagnosed, comprising 18 benign and 52 malignant lesions. Twenty-three qualitative and quantitative CT variables were evaluated using univariate and stepwise multivariate analyses, respectively. Two variables, namely, the postcontrast enhancement pattern of the lesion in the delayed phase (heterogeneous; odds ratio (OR): 14.7, 95% confidence interval (CI): 0.82-262.03, P=0.0429) and the maximal transverse diameter of the lesion (>4.5 cm; OR: 33.3, 95% CI: 2.29-484.18, P=0.0006), were significantly related to the differentiation of benign from malignant liver lesions, with an area under the curve of 0.8910, representing an accuracy of 88.6%. These findings indicate that features from triple-phase CT can provide information for distinguishing pathological varieties of focal liver lesions and for clinical decision making. Evaluations of the maximal transverse diameter and postcontrast enhancement pattern of the lesion included simple CT features for predicting liver malignancy with high accuracy in clinical settings.

Inflammatory colorectal polyp (ICRP) is an emerging disease in Miniature Dachshunds (MDs). Animals with this disease exhibit multiple polyps with severe neutrophil infiltration that respond to immunosuppressive therapy. Macrophages in polypoid lesions have been described to play an important role in neutrophil infiltration in the lesion by producing IL-8. In contrast, IL-10, an anti-inflammatory cytokine, was also reported to be upregulated in polypoid lesions, but its significance in the pathogenesis of ICRP has not been clarified. Regulatory T cells (Tregs) are the main source of IL-10 production and contribute to the maintenance of intestinal homeostasis. Therefore, the objective of this research was to compare the distribution of Tregs in polypoid lesions of ICRPs and the association between the distribution and expression of pro- or anti-inflammatory cytokines. Tissue biopsy specimens of polypoid lesions were collected from 28 MDs with ICRP. Those of macroscopically non-polypoid colonic mucosa from 24 MDs with ICRPs and 21 control dogs were further included as controls. Real-time quantitative polymerase chain reaction was used to quantify gene expression of IL-1β, IL-4, IL-6, IL-8, IL-10, IL-17, IL-22, IFN-γ, TNF-α, TGF-β, and forkhead box protein P3 (Foxp3) in each tissue sample. The numbers of Foxp3-positive cells (Tregs) and ionized calcium binding adapter molecule 1 (Iba-1)-positive cells (macrophages) were determined by immunohistochemistry. The gene expression of IL-1β, IL-6, IL-8, TNF-α, IFN-γ, IL-17, IL-10, TGF-β, and Foxp3 was significantly upregulated in polypoid lesions relative to control levels. The numbers of Foxp3-positive Tregs and Iba-1-positive macrophages were significantly increased in polypoid lesions compared to those in the non-polypoid colonic mucosa of MDs with ICRPs and control dogs. The upregulation of IL-10 was moderately correlated with the distribution of Tregs in polypoid lesions from MDs with ICRPs. In addition, the relative upregulation of IL-1β, IL-6, and IL-8 in polypoid lesions, compared to expression in non-polypoid colonic mucosa of MDs with ICRPs, was significantly greater than that of IL-10. These results indicate that increases in Treg numbers and anti-inflammatory cytokines in polypoid lesions comprise reactive changes in response to the inflammation, which warrants further investigation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A 12-year-old neutered female American cocker spaniel weighing 9.9 kg was presented for evaluation with a 2-day history of dyspnea and anorexia. Echocardiography revealed severe pulmonary hypertension (estimated systolic pulmonary arterial pressure, 93.4 mmHg) with right heart enlargement, pulmonary arterial dilation, and right ventricular dysfunction. The dilation of left heart and congenital cardiac shunt were not observed. Pulmonary thromboembolism (PTE) was confirmed by computed tomographic angiography. After treatment with antiplatelet and anticoagulant, the clinical sign and the echocardiographic abnormality of right heart were improved. These echocardiographic findings are not specific for PTE, but it can be useful as a rule-in test for PTE when other causes of pulmonary hypertension are excluded and a monitor of therapeutic efficacy.

In acidosis, catecholamines are attenuated, and higher doses are often required to improve cardiovascular function. Colforsin activates adenylate cyclase in cardiomyocytes without beta-adrenoceptor. Here, six beagles were administered colforsin or dobutamine four times during eucapnia (partial pressure of arterial carbon dioxide 35-40 mm Hg; normal) and hypercapnia (ibid 90-110 mm Hg; acidosis) conditions. The latter was induced by CO2 inhalation. Anesthesia was induced with propofol and maintained with isoflurane. Cardiovascular function was measured by thermodilution and a Swan-Ganz catheter at baseline and 60 min after 0.3 μg/kg/min (low), 0.6 μg/kg/min (middle), and 1.2 μg/kg/min (high) colforsin administration. The median pH was 7.38 [range 7.33-7.42] and 7.01 [range 6.96-7.08] at baseline in the Normal and Acidosis conditions, respectively. Endogenous adrenaline and noradrenaline levels at baseline were significantly (P < 0.05) higher in the Acidosis than in the Normal condition. Colforsin induced cardiovascular effects similar to those caused by dobutamine. Colforsin increased cardiac output in the Normal condition (baseline: 3.9 ± 0.2 L/kg/m2 [mean ± standard error], low: 5.2 ± 0.4 L/kg/min2, middle: 7.0 ± 0.4 L/kg/m2, high: 9.4 ± 0.2 L/kg/m2; P < 0.001) and Acidosis condition (baseline: 6.1 ± 0.3 L/kg/m2, low: 6.2 ± 0.2 L/kg/m2, middle: 7.2 ± 0.2 L/kg/m2, high: 8.3 ± 0.2 L/kg/m2; P < 0.001). Colforsin significantly increased heart rate and decreased systemic vascular resistance compared to values at baseline. Both drugs increased pulmonary artery pressure, but colforsin (high: 13.3 ± 0.6 mmHg in Normal and 20.1 ± 0.2 mmHg in Acidosis) may have lower clinical impact on the pulmonary artery than dobutamine (high: 19.7 ± 0.6 in Normal and 26.7 ± 0.5 in Acidosis). Interaction between both drugs and experimental conditions was observed in terms of cardiovascular function, which were similarly attenuated with colforsin and dobutamine under acute respiratory acidosis., Competing Interests: The authors have declared that no competing interests exist.

The objective of this study was to examine the effects of immunosuppressive prednisolone therapy on pancreatic tissue and the concentration of serum canine pancreatic lipase immunoreactivity (cPLI) in healthy dogs. Six healthy beagle dogs were subcutaneously administered an immunosuppressive dose of prednisolone [4 mg/kg body weight (BW)] once daily for either 2 or 3 weeks. Serum cPLI concentration was measured before and after treatment. Ultrasonographic examination of the pancreas and laparoscopic biopsy and histopathological examination of the right pancreatic lobe and the liver were also conducted before and after treatment. The expression of pancreatic lipase messenger ribonucleic acid (mRNA) in the pancreas and liver was examined by polymerase chain reaction (PCR). Although the serum cPLI concentration was significantly higher on day 14 and on the day of the second laparoscopy than before treatment, it was classified as normal (≤ 200 μg/L) in 5 dogs and as abnormal (≥ 400 μg/L) in only 1 dog. None of the 6 dogs showed clinical signs of pancreatitis during the study period. After treatment, ultrasonographic examination of the pancreas showed no changes except for a hypoechoic pancreas in 1 dog. Histopathological examination of the right pancreatic lobe in all dogs showed no evidence of pancreatitis after treatment. Pancreatic lipase mRNA expression was detected in the pancreas, but not in the liver, before and after treatment. The administration of 4 mg/kg BW per day of prednisolone for 2 or 3 weeks increased the serum cPLI concentration without clinical signs of pancreatitis, although an abnormal cPLI concentration (≥ 400 μg/L) was observed in only 1 dog. No ultrasonographic or histological evidence of pancreatitis was observed in any of the dogs.

A 10-year-old cat presented for evaluation with a 1-month history of salivation and oral bleeding. A right mandibular mass was palpated and computed tomography examination revealed entire bone proliferation. Mandibular bone biopsy was performed, and histopathological diagnosis was vascular hamartoma. The cat suddenly died on day 140.

Changes in stroke volume variation (SVV) and pulse pressure variation (PPV) in response to fluid infusion were experimentally evaluated during vecuronium infusion and sevoflurane anesthesia in 5 adult, mechanically ventilated, euvolemic, beagle dogs. Sequential increases in central venous pressure (CVP; 3-7[baseline], 8-12, 13-17, 18-22 and 23-27 mmHg) were produced by infusing lactated Ringer's solution and 6% hydroxyethyl starch solution. Heart rate (beats/min), right atrial pressure (RAP, mmHg), pulmonary arterial pressure (PAP, mmHg), pulmonary capillary wedge pressure (PCWP, mmHg), transpulmonary thermodilution cardiac output (TPTDCO, l/min), stroke volume (SV, ml/beat), arterial blood pressure (ABP, mmHg), extravascular lung water (EVLW, ml), pulmonary vascular permeability index (PVPI, calculated), SVV (%), PPV (%) and systemic vascular resistance (SVR, dynes/sec/cm 5 ) were determined at each predetermined CVP range. Heart rate (P=0.019), RAP (P<0.001), PAP (P<0.001), PCWP (P<0.001), TPTDCO (P=0.009) and SV (P=0.04) increased and SVR (P<0.001), SVV (P<0.001) and PPV (P<0.001) decreased associated with each stepwise increase in CVP. Arterial blood pressure, EVLW, PVPI and the arterial partial pressures of oxygen and carbon dioxide did not change. The changes in SVV and PPV directly reflected the fluid load and the minimum threshold values for detecting fluid responsiveness were SVV ≥11% and PPV ≥7% in dogs.

Objective: To evaluate the agreement between cardiac output (CO) values obtained using a transpulmonary thermodilution technique (TPTDCO) and conventional thermodilution technique (TDCO) in anaesthetized dogs with fluid overload., Study Design: Prospective experimental study., Animals: Six healthy Beagle dogs aged 7-8 years., Methods: Dogs were anaesthetized with sevoflurane in oxygen, and catheters were inserted for TPTDCO and TDCO measurement. After instrumentation, baseline CO was measured using each technique at a central venous pressure (CVP) of 3-7 mmHg. Dogs were subsequently administered lactated Ringer's solution and 6% hydroxyethyl starch to induce fluid overload. CO measurements were obtained using each technique at CVP values of 8-12 mmHg, 13-17 mmHg, 18-22 mmHg and 23-27 mmHg. Agreements between CO measurements obtained with the respective techniques were analysed using Dunnett's test, Pearson's correlation coefficient and Bland-Altman analysis., Results: Thirty pairs of CO values were obtained, ranging from 1.45 L minute(-1) to 4.69 L minute(-1) for TPTDCO and from 1.30 L minute(-1) to 4.61 L minute(-1) for TDCO. TPTDCO and TDCO values correlated strongly (r(2)  = 0.915, p < 0.001). The bias and mean relative bias between TPTDCO and TDCO were 0.26 ± 0.30 L minute(-1) (limits of agreement - 0.29 to 0.81 L minute(-1) ) and 9.7%, respectively., Conclusions and Clinical Relevance: TPTDCO and TDCO measurements obtained in anaesthetized dogs during fluid overload exhibited good agreement. Accordingly, transpulmonary thermodilution provides an accurate measurement of CO in dogs with fluid overload., (© 2015 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.)

Porencephaly is the congenital cerebral defect and a rare malformation and described few MRI reports in veterinary medicine. MRI features of porencephaly are recognized the coexistence with the unilateral/bilateral hippocampal atrophy, caused by the seizure symptoms in human medicine. We studied 2 dogs and 1 cat with congenital porencephaly to characterize the clinical signs and MRI, and to discuss the associated MRI with hippocampal atrophy. The main clinical sign was the seizure symptoms, and all had hippocampal atrophy at the lesion side or the larger defect side. There is association between hippocampal atrophy or the cyst volume and the severe of clinical signs, and it is suggested that porencephaly coexists with hippocampal atrophy as well as humans in this study.

Haemangiosarcoma (HSA) is an important malignant neoplasm of dogs that originates from vascular endothelial cells. This study explored the suitability of using serum big endothelin-1 (ET-1) as a tumour marker for canine spontaneous HSA. Serum big ET-1 was measured in dogs with splenic HSA (n = 14), splenic malignant tumours other than HSA (n = 10), benign splenic lesions (n = 11) and normal healthy dogs (n = 17) by ELISA. Serum big ET-1 levels in dogs with HSA were significantly (P < 0.01) higher than in other dogs. High sensitivity (100%, 95% confidence interval 86-100%) and specificity (95%, 95% confidence interval 86-95%) for HSA diagnosis were obtained using a cut-off of 17 pg/mL according to receiver operating characteristic (ROC) curves (area under ROC curve 0.93). PPET1, ETA, VEGF and Hif1-α mRNA expression, measured by real-time PCR, were elevated in HSA compared with normal tissues. These findings suggest that elevated serum big ET-1 could be used as a diagnostic marker for canine HSA., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Transitional cell carcinoma (TCC), a urinary bladder tumor with high mortality, is encountered commonly in dogs. Whereas overexpression of epidermal growth factor receptor (EGFR) is associated with development of human urinary bladder cancer, information on EGFR expression in canine TCC is lacking. In this study, EGFR protein and mRNA expression in canine normal bladder (n=5), polypoid cystitis (n=5) and TCC (n=25) were examined by immunohistochemistry and real-time polymerase chain reaction. EGFR protein expression was significantly higher in TCC than that in normal healthy bladder (P<0.001) and polypoid cystitis (P<0.005). High EGFR protein expression was significantly (P<0.01) associated with TCC with a sensitivity of 72% and specificity of 100%. Comparative analysis of protein and mRNA expression levels in TCC showed significant positive correlation (r=0.88, P<0.05) between mRNA and protein expression. These findings suggest that intense expression of EGFR protein could be used as a marker to help canine TCC diagnosis.

Aims: Many studies of human subjects have demonstrated the utility of assessing serum levels of endothelin-1 (ET-1) and big ET-1 as clinical biomarkers in cardiopulmonary and neoplastic diseases. In this study we explored the feasibility of using serum big ET-1 as a reliable veterinary marker in dogs with various cardiopulmonary and neoplastic diseases., Main Methods: Serum big ET-1 levels were measured by ELISA in dogs with cardiopulmonary (n=21) and neoplastic diseases (n=57). Dogs exhibiting cardiopulmonary disease were divided into two groups based on the velocity of tricuspid valve regurgitation (3.0>m/s) measured by ultrasound: without and with pulmonary hypertension. Big ET-1 levels for the dogs with the diseases were compared with levels in normal healthy dogs (n=17)., Key Findings: Dogs with cardiopulmonary disease (4.6±4.6 pmol/l) showed a significantly (P<0.01) higher level of big ET-1 than healthy control dogs (1.1±0.53 pmol/l). Serum levels in the dogs with pulmonary hypertension (6.2±5.3 pmol/l) were significantly (P<0.01) higher than those without pulmonary hypertension (2.0±0.6 pmol/l). Dogs with hemangiosarcoma (5.6±2.2 pmol/l), adenocarcinoma (2.0±1.8 pmol/l), histiocytic sarcoma (3.3±1.9 pmol/l), chondrosarcoma or osteosarcoma (3.0±1.6 pmol/l) and hepatocellular carcinoma (2.7±1.8 pmol/l) showed significantly (P<0.05) higher levels than healthy control dogs., Significance: These findings point to the potential of serum big ET-1 as a clinical marker for cardiopulmonary and neoplastic diseases in dogs., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

In human bladder cancer patients, ultrasonography is extensively used not only to identify tumor masses but also to evaluate tumor size, shape, echogenicity, location, and degree of tumor invasion into the bladder wall. The information revealed by ultrasonography delineates the tumor's biological features and facilitates prediction of prognosis. However, in veterinary medicine the feasibility of using ultrasonography for these purposes has not been fully investigated. In this retrospective study, we reviewed cases of dogs with histologically confirmed bladder mass lesions, including transitional cell carcinoma (n = 22) and polypoid cystitis (n = 5), to determine whether ultrasonography could reliably predict bladder wall involvement. By following patients with transitional cell carcinoma until death, we also determined whether ultrasonographic tumor size, shape, echogenicity, and mass location were related to prognosis. Wall involvement as revealed by ultrasound was significantly (P = 0.00005) associated with histological muscular layer involvement with a sensitivity of 93% (95% Confidence interval, 79-98%) and specificity of 92% (95% Confidence interval, 76-98%). Ultrasonographic wall involvement (P = 0.03, vs. noninvolvement), heterogeneous mass (P = 0.02, vs. homogeneous mass), and trigone location (P = 0.01, vs. other locations) characteristics were significantly associated with shorter survival times in transitional cell carcinoma cases. Findings indicated that ultrasonographic characteristics such as wall involvement, heterogeneous mass, and trigone location could be reliable prognostic indicators in canine transitional cell carcinoma., (© 2013 American College of Veterinary Radiology.)

L-type amino acid transporter 1 (LAT1), an isoform of amino acid transport system L, transports branched or aromatic amino acids essential for fundamental cellular activities, such as cellular growth, proliferation and maintenance. LAT1 has recently received attention because of its preferential and upregulated expression in a variety of human tumours which is in contrast to its limited distribution and low-level expression in normal tissues. In this study, the feasibility of using an LAT1 inhibitor as a new therapeutic agent was explored for mammary gland tumours (MGT). [(3)H]l-leucine uptake by CHM, a cell line established from MGT, and effects on cell growth were analysed in the presence or absence of two LAT1 inhibitors, namely, BCH (2-amino-2-norbornane-carboxylic acids) or melphalan (LPM). [(3)H]l-leucine uptake and cellular growth activities in CHM were inhibited in a dose-dependent manner by both LAT1 inhibitors. The inhibitory growth activities of various conventional anti-cancer drugs used for MGT treatment, including carboplatin, cyclophosphamide, doxorubicin, mitoxantrone, vinblastine and vincristine, were significantly enhanced by combining use with BCH or LPM. The findings suggest that LAT1 could be a new therapeutic target for canine MGT., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

L-type amino acid transporter 1 (LAT1), an isoform of amino acid transport system L, transports branched or aromatic amino acids essential for fundamental cellular activities such as cellular growth, proliferation and maintenance. This amino acid transporter recently has received attention because of its preferential and up-regulated expression in a variety of human tumors in contrast to its limited distribution and low-level expression in normal tissues. In this study, we explored the feasibility of using LAT1 inhibitor as a new therapeutic agent for human malignant melanomas (MM) using canine spontaneous MM as a model for human MM. A comparative study of LAT expression was performed in 48 normal tissues, 25MM tissues and five cell lines established from MM. The study observed LAT1 mRNA levels from MM tissues and cell lines that were significantly (P<0.01) higher than in normal tissues. Additionally, MM with distant metastasis showed a higher expression than those without distant metastasis. Functional analysis of LAT1 was performed on one of the five cell lines, CMeC-1. [(3)H]l-Leucine uptake and cellular growth activities in CMeC-1 were inhibited in a dose-dependent manner by selective LAT1 inhibitors (2-amino-2-norbornane-carboxylic acid, BCH and melphalan, LPM). Inhibitory growth activities of various conventional anti-cancer drugs, including carboplatin, cyclophosphamide, dacarbazine, doxorubicin, mitoxantrone, nimustine, vinblastine and vincristine, were significantly (P<0.05) enhanced by combination use with BCH or LPM. These findings suggest that LAT1 could be a new therapeutic target for MM., (Copyright © 2013 Elsevier Inc. All rights reserved.)

L-type amino acid transporter 1 (LAT1), an isoform of amino acid transport system L, transports branched or aromatic amino acids essential for fundamental cellular activities such as cellular growth, proliferation and maintenance. This amino acid transporter recently has received attention because of its preferential and up-regulated expression in a variety of human tumors, in contrast to its limited distribution and low-level expression in normal tissues. In this study, to explore the feasibility of using LAT1 expression as a molecular marker in mammary gland tumors (MGT), we performed a comparative study of LAT1 expression at the mRNA and protein levels in normal mammary gland cells and tumor cells. Conventional RT-PCR and Western blotting were performed on MGT tissues from 16 dogs and normal organs from nine healthy dogs. LAT1 expression was detected in ten of the 16 MGT patients. As is the case in human tissues, LAT1 showed limited expressional distribution in normal canine organs. For quantitative expressional comparison, extensive real-time RT-PCR was performed on mRNA samples from 53 MGT patients. The comparison demonstrated that LAT1 mRNA levels from MGT tissues were 20 times higher than those in normal mammary gland tissues. Additionally, histologically invasive MGT showed a higher expression of LAT1 than non-invasive tumors. These findings suggest that LAT1 could be a clinical marker and therapeutic target for invasive malignant MGT.

Gastrointestinal stromal tumor (GIST), a mesenchymal neoplasm affecting the gastrointestinal tract, shows a variety of clinical behaviors from inactive benign to aggressive malignant in dogs. In this study, the feasibility of using clinically significant ultrasonographic features to predict the metastatic potential of canine GIST was investigated through comparison with actual metastatic incidence and findings of malignancy obtained by postoperative pathological examination. Ultrasonographic features, including large tumor size, irregular margin and heterogeneous internal echogenicity with large hypoechoic areas, related closely with the presence of metastasis as well as a high-risk ranking by the human classification system according to pathological findings. Based on these ultrasonographic features, the potential of metastasis in canine GIST could be preoperatively predicted.

To evaluate the relationship among immune status and increased morbidity and mortality, peripheral blood lymphocytes (CD3(+), CD4(+), CD8(+) and CD21(+) cells) from 32 healthy dogs over 8 years of age were analyzed. Twenty-five of the 32 dogs were followed-up for 3 years after the analysis; and 14 dogs were found to be diseased, and nine dogs died. There was no notable difference between the ages of the dogs that died compared with the ones that survived. The relative percentage of CD4(+) and the CD4(+):CD8(+) ratio decreased notably in dogs falling ill compared with healthy dogs. The relative percentage of CD3(+) lymphocytes showed a notable decrease in dogs that died within 3 years in comparison with dogs that survived. In a discriminant analysis of morbidity and mortality, most patients were correctly classified as diseased or not and surviving or dead, respectively. These results indicate that the immunophenotypes of peripheral blood lymphocytes in older dogs offer promise as parameters for evaluating mortality and morbidity.

Contrast-enhanced magnetic resonance (MR) imaging with a new liver-specific contrast agent gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA; EOB·Primovist®) was studied in 14 normal beagles and 9 dogs with focal liver lesions. Gd-EOB-DTPA accumulates in normally functioning hepatocytes 20 min after injection. As with Gd-DTPA, it is also possible to perform a dynamic multiphasic examination of the liver with Gd-EOB-DTPA, including an arterial phase and a portal venous phase. First, a reliable protocol was developed and the appropriate timings for the dynamic study and the parenchymal phase in normal dogs using Gd-EOB-DTPA were determined. Second, the patterns of these images were evaluated in patient dogs with hepatic masses. The optimal time of arterial imaging was from 15 s after injection, and the optimal time for portal venous imaging was from 40 s after injection. Meanwhile, the optimal time to observe changes during the hepatobiliary phase was from 20 min after injection. In patient dogs, 11 lesions were diagnosed as malignant tumors; all were hypointense to the surrounding normal liver parenchyma during the hepatobiliary phase. Even with a low-field MR imaging unit, the sequences afforded images adequate to visualize the liver parenchyma and to detect tumors within an appropriate scan time. Contrast-enhanced MR imaging with Gd-EOB-DTPA provides good demarcation on low-field MR imaging for diagnosing canine focal liver lesions., (© 2012 Veterinary Radiology & Ultrasound.)

A 7-year-old, male, mixed breed dog was referred to the Veterinary Teaching Hospital at Kitasato University because of anorexia, lameness and multiple cutaneous lesions. Observation of bone marrow plasmacytosis, osteolytic bone lesions, serum myeloma protein and cutaneous infiltration of myeloma cells led us to a diagnosis of multiple myeloma (MM) with cutaneous involvement. Polymerase chain reaction and sequence analysis for the rearranged genes of immunoglobulin and T-cell receptor demonstrated that the neoplastic cells found in skin lesions or bone marrow are of B-lymphocyte lineage and share a common original precursor cell. The dog was treated with UW-Madison protocol or melphalan/prednisone protocol and survived 175 days. This is rare case of anaplastic MM with cutaneous involvement in dog.

The chemokine CXCL12, also known as stromal cell-derived factor-1 and its receptor CXCR4 have been shown to play prominent roles in regulating the directional migration and proliferation of various types of cancer cells during the metastatic process. However, few researchers have examined the expression of CXCL12 and CXCR4 and their prognostic value in patients with esophageal squamous cell carcinoma (ESCC). We investigated immunohistochemically the relationship between CXCL12 and CXCR4 expression and clinicopathological factors including prognosis in surgical specimens of primary tumors in 214 patients with ESCC. The positive expression rate of CXCL12 was 53.7% and that of CXCR4 was 84.6%. Positive CXCL12 expression was significantly correlated with lymph node metastasis, tumor stage, gender and lymphatic invasion. The overall and disease-free survival rate was significantly lower in patients with positive CXCL12 expression than in those with negative CXCL12 expression. The expression of CXCR4 had no correlation with clinicopathological variables and prognosis. We showed that positive CXCL12 expression was related to a greater degree to tumor development, compared with CXCR4 expression. Evaluation of CXCL12 expression is useful for determining tumor properties, including nodal metastasis and prognosis in patients with ESCC.

We report the case of a 56-year-old male who was diagnosed as advanced esophageal cancer with esophago-pulmonary fistula and lung abscess. He received radiation therapy in combination with chemotherapy using cisplatin and 5-FU after insertion of a self-expanding metallic stent. He had sufficient food intake during the chemoradiotherapy (CRT). CRT was very effective for not only primary tumor but also lymph node metastasis, with resulting partial response. We could not detect any relapses and metastases for 8 months after CRT. The CRT after insertion of self-expanding metallic stent is one of the useful and palliative treatments for advance esophageal cancer with esophago-pulmonary fistula.

Mutations of p53, a tumor suppressor gene, are known to be involved in the pathogenesis of a number of neoplasms. This study investigated the distribution of p53 mutations within both esophageal and gastric adenocarcinomas. The correlation between p53 mutations and an overexpression of p53, which has been reported by other researchers, was also explored. Samples were taken from 17 patients following a surgical resection of the tumor. The patients included 8 cases of adenocarcinoma from the cardia (esophagogastric junction) and 9 cases of gastric carcinoma. Two or three samples were taken from each tumor, plus samples of normal tissue from the patient. Denaturing high pressure liquid chromatography (DHPLC) was employed to detect p53 mutations, and samples found to have mutations were then sequenced. The expression of p53 was determined by immunohistochemistry. DHPLC demonstrated that 37.5% (3/8) of esophageal carcinomas and 44.4% (4/9) of gastric carcinomas have p53 mutations. DNA sequencing showed the same mutation to be present in all of the samples from each tumor, while the corresponding normal tissue was free from mutations (except for 2 cases of polymorphism). The results of immunohistochemistry did not demonstrate a relationship between p53 mutations and the expression of p53 protein, and only 4 of the 7 tumors with p53 mutations showed a positive result. These findings support the hypothesis that p53 mutations are homogeneous throughout a tumor and may thus be a more useful diagnostic and prognostic indicator than the expression of p53, which does not reliably correlate with p53 mutations.

A case of esophageal cancer associated with the right aortic arch in a 62-year-old Japanese male is described herein. Endoscopy performed after an initial complaint of dysphagia revealed cancer at the upper third of the esophagus. The right aortic arch was located by routine chest X-ray and an irregularly-shaped tumor defect and a shadow defect due to right aortic arch were detected on the right side of the thoracic esophagus by barium study. Computed tomography and magnetic resonance imaging offered useful information for surgical procedure. The patient underwent a subtotal esophagectomy and regional lymphadenectomy though a left thoracotomy. The clinical features of cases previously reported in Japan are reviewed following the presentation of this case.

Suplatast tosilate (IPD) is a Th2 cytokine inhibitor that lowers the titer of the IgE antibody through specific inhibition of the production of IL (interleukin)-4 and IL-5 by T cells and inhibits tissue infiltration by eosinophils. In this clinical trial, suplatast tosilate (300 mg/day) was administered orally for 4 weeks to 25 patients (13 patients with atopic asthma, 12 patients with nonatopic asthma) whose bronchial asthma was staged in step 1 or step 2 according to the Guidelines for Prevention and Management of Bronchial Asthma, 1998. Before and after administration, the parameters of airway inflammation, that is, peripheral blood eosinophils count, serum level of eosinophil cationic protein (ECP), ECP level in induced sputum, airway hyperresponsiveness (Dmin), and morning peak expiratory flow (PEF), were measured. The peripheral blood eosinophil count, serum level of ECP, and ECP level in induced sputum decreased significantly. Of these parameters, the ECP level in induced sputum was the most sensitive. Furthermore, suplatast tosilate significantly inhibited Dmin. These results were especially significant in patients with atopic asthma. Suplatast tosilate was considered to have inhibited airway eosinophilic inflammation through decreases in peripheral blood eosinophils counts and in ECP levels in induced sputum, which resulted in inhibition of airway hyperresponsiveness.