A splice site variant in the SUV39H2 gene in Greyhounds with nasal parakeratosis.

Hereditary nasal parakeratosis (HNPK), described in the Labrador Retriever breed, is a monogenic autosomal recessive disorder that causes crusts and fissures on the nasal planum of otherwise healthy dogs. Our group previously showed that this genodermatosis may be caused by a missense variant located in the SUV39H2 gene encoding a histone 3 lysine 9 methyltransferase, a chromatin modifying enzyme with a potential role in keratinocyte differentiation. In the present study, we investigated a litter of Greyhounds in which six out of eight puppies were affected with parakeratotic lesions restricted to the nasal planum. Clinically and histologically, the lesions were comparable to HNPK in Labrador Retrievers. Whole genome sequencing of one affected Greyhound revealed a 4-bp deletion at the 5'-end of intron 4 of the SUV39H2 gene that was absent in 188 control dog and three wolf genomes. The variant was predicted to disrupt the 5'-splice site with subsequent loss of SUV39H2 function. The six affected puppies were homozygous for the variant, whereas the two non-affected littermates were heterozygous. Genotyping of a larger cohort of Greyhounds revealed that the variant is segregating in the breed and that this breed might benefit from genetic testing to avoid carrier × carrier matings.

Fibroblastic Subtype has a Favourable Prognosis in Appendicular Osteosarcoma of Dogs.

Osteosarcoma (OS) is an aggressive malignant bone neoplasm that occurs mostly in the appendicular skeleton of dogs and people. OS is classified based on the presence of malignant stroma and the formation of extracellular matrix into osteoblastic, chondroblastic and fibroblastic forms. This study investigated the correlation between the three histological subtypes of canine OS and clinical outcome. Additionally, we examined whether there was any difference in the immunolabelling of desmin, S100 and neuron-specific enolase (NSE) between the three histological subtypes. Formalin-fixed and paraffin wax-embedded tissues from 87 dogs with primary OS were available for this study. The survival times were correlated with appendicular OS subtypes in dogs that were treated surgically, received adjuvant chemotherapy and had no pulmonary metastasis at the time of diagnosis. Dogs with an appendicular fibroblastic OS had significantly prolonged mean average survival times (546 ± 105 days) in comparison with dogs having appendicular osteoblastic (257 ± 48 days) or appendicular chondroblastic (170 ± 28 days) OS (P = 0.003, Log Rank). The results also revealed that the appendicular chondroblastic subtype is a significant indicator for poor prognosis in dogs compared with the fibroblastic or osteoblastic subtypes (P = 0.006, Cox regression). Moreover, the findings indicated that there was no significant correlation between the localization of desmin, NSE or S100 and histological subtypes. Importantly, dogs with appendicular fibroblastic OS were found to have a better prognosis when compared with dogs with other subtypes. This may suggest that histological subtypes of appendicular OS have diverse behaviour and could be used to categorize patients for risk-based assessment.

Fatal encephalitozoonosis in two koalas.

Two young koalas from a fauna park, recently out of the pouch and approximately 6 months old, were found dead with no previous clinical signs or gross lesions. On histopathological examination, large numbers of spores consistent with a microsporidian organism were present intracellularly within the small intestinal mucosa. Electron microscopy and polymerase chain reaction studies (sequencing the 5' end of the SSU RNA gene) identified the organism as Encephalitozoon intestinalis with 100% homology with those of previously reported human isolates. This is believed to be the first report of this organism in a marsupial.

Canine Mixed Mammary Tumour as a Model for Human Breast Cancer with Osseous Metaplasia.

Canine mixed mammary tumours (CMMTs) and human metaplastic breast carcinomas (HMBCs) share several histopathological features and risk factors. In both species, these tumours display epithelial and stromal components. HMBCs are rare malignant tumours, but CMMTs are one of the most common mammary tumours in dogs and are more often benign than malignant. In this study, benign (n = 88) and malignant (n = 13) CMMTs were characterized using specific antibodies against oestrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, cytokeratin 5/6, cytokeratin AE1/AE3, vimentin, Ki67, E-cadherin and p63. Cartilage and bone matrices associated with benign and malignant CMMTs were characterized using specific antibodies against BMP4, Runx2, Sox9 and osteopontin. The current study suggested that CMMTs are of epithelial origin, but display a myoepithelial-like differentiation. The findings suggest key roles for Sox9, Runx2 and BMP4 in chondrogenesis and bone formation in CMMTs. The high expression of osteopontin in CMMTs appears to be unrelated to tumour malignancy.

Pacemaker lead perforation of the right ventricle associated with Moraxella phenylpyruvica infection in a dog.

CASE DESCRIPTION: A 13-year-old neutered male Border Collie was presented with acute onset syncope, weakness and anorexia 10 months after transvenous pacemaker implantation. The patient was laterally recumbent, bradycardic (36 beats/min) and febrile (40.7°C) on presentation. An electrocardiogram (ECG) revealed recurrence of third-degree atrioventricular block with a ventricular escape rhythm. Fluoroscopy identified migration of the pacemaker tip through the apex of the right ventricle. Echocardiography failed to reveal any evidence of pericardial effusion or cardiac tamponade. Full postmortem was performed after euthanasia. The pacemaker lead had perforated the apex of the right ventricle and lodged in the right pleural space. Culture of blood (taken antemortem), pericardial sac, right ventricular wall (surrounding pacemaker lead), pacemaker lead tip and pericardial fluid revealed a pure growth of Moraxella phenylpyruvica. CONCLUSION: Bacteraemia associated with M. phenylpyruvica has never been reported in the dog, but sporadic cases are reported in humans. Infection could have resulted from either pre-existing myocarditis or opportunistic infection and bacteraemia post pacemaker implantation. Evaluation of the pacemaker function at regular intervals would allow early detection of poor pacemaker-to-myocardium contact, which would prompt further investigation of pacemaker lead abnormalities such as perforation.

The dependence of paracetamol absorption on the rate of gastric emptying.

1. The rate of gastric emptying was measured directly in 14 convalescent hospital patients and paracetamol absorption was studied following an oral dose of 1.5 g.2. Rapid gastric emptying was associated with the early appearance of high peak plasma paracetamol concentrations whereas peak concentrations were low and occurred late when gastric emptying was slow.3. There was a significant correlation between the rate of gastric emptying and the 0-4 and 0-24 h urinary excretion of paracetamol and its metabolites.4. In five patients with abnormally slow gastric emptying the mean maximum plasma concentration and 0-4 and 0-24 h urinary excretion of paracetamol were significantly lower than in seven patients with normal gastric emptying rates while the time taken to reach maximum plasma concentrations was longer.5. Individual differences in the rate of gastric emptying may contribute to variable absorption of many drugs.

Expression of CD45 isoforms in chronic B-cell leukaemias.

CD45 isoform expression was studied in 204 cases of B-cell lymphoproliferative disease, including 162 chronic lymphocytic leukaemia (CLL). In almost half the samples tested, CD45R0 was co-expressed with CD45RA, unlike normal B-cells, which express only CD45RA, except at terminal stages of differentiation. In a small number of cases CD45R0 was the dominant isoform expressed. No correlation could be discerned either with Binet or RAI staging in CLL or with disease type CLL, prolymphocytic leukaemia (PLL) or hairy cell leukaemia (HCL). Comparison of CD45 isoform expression with other markers showed no correlation with apparent maturational status of the cells involved.

Hairy cell leukemia cells are relatively NK-insensitive targets.

The hypothesis that interferon alpha (IFN alpha) has its beneficial effects in hairy cell leukemia by activating natural killer cells against hairy cells was examined. Leukemic cells from patients with hairy cell leukemia were tested for their susceptibility to lysis by fresh and IFN alpha activated peripheral blood mononuclear (PBMC) cells from normal donors. All hairy cells tested were relatively insensitive to cytolysis by PBMC and IFN alpha activated PBMC. The low levels of 51Cr release obtained with a few donors was due to lysis of leukemic cells, not residual normal cells, and was mediated by a natural killer cell (T cell receptor independent) mechanism. Chronic lymphatic leukemic cells before and after treatment with phorbol ester were also resistant to cytolysis. Hairy cells were not susceptible to lymphokine activated killer (LAK) cells but were sensitive to lysis by antibody and complement. The insensitivity to cell mediated cytolysis against hairy cells was shown by cold target inhibition to be a lack of target recognition by NK cells.

Sasa-Satsuma higher-order nonlinear Schrödinger equation and its bilinearization and multisoliton solutions.

Higher-order and multicomponent generalizations of the nonlinear Schrödinger equation are important in various applications, e.g., in optics. One of these equations, the integrable Sasa-Satsuma equation, has particularly interesting soliton solutions. Unfortunately, the construction of multisoliton solutions to this equation presents difficulties due to its complicated bilinearization. We discuss briefly some previous attempts and then give the correct bilinearization based on the interpretation of the Sasa-Satsuma equation as a reduction of the three-component Kadomtsev-Petviashvili hierarchy. In the process, we also get bilinearizations and multisoliton formulas for a two-component generalization of the Sasa-Satsuma equation (the Yajima-Oikawa-Tasgal-Potasek model), and for a (2+1)-dimensional generalization.

From river to ridge: a blueprint for sustainable management in the Georges River catchment.

Research on sustainable transport and water projects, conducted in North America during 1999, identified four key considerations common to a number of projects. These four considerations are the preconditions necessary to achieve sustainability in a given location. These preconditions (BAPP) are boundary definition, administrative alignment, protection of non-urban lands, and the participation of all interested parties. This paper considers the perceived attitudes of various catchment stakeholders and focuses on planners and planning. The results of questionnaire surveys based on BAPP concepts suggest that local government is perceived as having the highest priority for protection of riparian lands and waterways (as individual Councils and Regional Organisations of Councils). Thus local government is the preferred arena for coordination, responsibility and jurisdiction of waterways and riparian land. The opportunity exists to examine the differing roles of local and state government. The paper concludes by outlining the implications of this research for land use planning and institutional structures in sustainable river management.

Case report: six cases of verminous pneumonia (Muellerius sp.) in goats.

Six cases of verminous pneumonia in goats due to Muellerius sp. were reviewed. In only one case was the pneumonia diagnosed antemortem. The gross necropsy findings and histopathology revealed a widespread interstitial pneumonia in all the cases. There was variability in the local reaction around the parasites from almost none in the mildest cases to larger focal accumulations of macrophages and mononuclear inflammatory cells. Only in the severest cases were eosinophils seen and even then were scattered and few in number. No nodular lesions were seen associated with the parasites. The pathology of the pulmonary lesions in goats appears to be more commonly of the diffuse type and therefore significantly different from the nodular lesion usually observed in sheep.

Syncope associated with swallowing in two British Bulldogs with unilateral carotid body tumours.

Carotid body tumours were diagnosed in two British Bulldogs that each had a history of syncopal episodes induced by eating, drinking or pulling on the leash. In both dogs, a cervical mass was identified using computed tomography (CT) or magnetic resonance imaging, with carotid body tumour (CBT) being the histopathological diagnosis. A heart base mass was also identified in one dog by both CT and echocardiography. Swallowing syncope has been reported in the human literature in association with cervical mass lesions, but this is the first report in dogs. The present cases emphasise the value of advanced imaging of the head and neck in dogs presenting with clinical signs of syncope associated with swallowing and the importance of careful manipulation of the neck in patients with CBTs.

Lythrum hyssopifolia (lesser loosestrife) poisoning of sheep in Victoria.

OBJECTIVE: To document an ovine disease attributed to the consumption of Lythrum hyssopifolia (lesser loosestrife). PROCEDURES: Historical and histological review of field and experimental cases. RESULTS: 1-20% mortality occurred in sheep flocks grazing paddocks where L. hyssopifolia was the predominant green vegetation. Well-documented disease outbreaks occurred in summer on nine farms across Victoria between 1974 and 2002. Liver damage occurred in all nine outbreaks, with kidney damage in at least eight. Hepatocyte necrosis was usually zonal to midzonal (zone 2) in the liver samples from four farms and periacinar (zone 3) in those from three farms, but some livers showed only single-cell necrosis. Multinucleate hepatocytes near necrotic areas were a feature in six cases. Proximal tubular epithelium appeared to be the primary renal target and brown granules were often present in renal tubules. Biochemical and histological evidence of liver and kidney damage was obtained from two sheep experimentally pen-fed harvested L. hyssopifolia. CONCLUSION: Chemicals in L. hyssopifolia are toxic to ovine hepatocytes and renal tubular epithelial cells.

The production of calcium and magnesium during pancreatic function tests in health and disease.

Duodenal calcium and magnesium concentrations after pancreatic stimulation were measured in 25 patients with and without pancreatic disease. The concentration of both ions was higher in those with pancreatic disease, and furthermore these patients showed a different secretory pattern. These findings may be relevant to the aetiology of pancreatitis and to pancreatic calcification, and might be of diagnostic value.