Canine NAPEPLD-associated models of human myelin disorders.

Canine leukoencephalomyelopathy (LEMP) is a juvenile-onset neurodegenerative disorder of the CNS white matter currently described in Rottweiler and Leonberger dogs. Genome-wide association study (GWAS) allowed us to map LEMP in a Leonberger cohort to dog chromosome 18. Subsequent whole genome re-sequencing of a Leonberger case enabled the identification of a single private homozygous non-synonymous missense variant located in the highly conserved metallo-beta-lactamase domain of the N-acyl phosphatidylethanolamine phospholipase D (NAPEPLD) gene, encoding an enzyme of the endocannabinoid system. We then sequenced this gene in LEMP-affected Rottweilers and identified a different frameshift variant, which is predicted to replace the C-terminal metallo-beta-lactamase domain of the wild type protein. Haplotype analysis of SNP array genotypes revealed that the frameshift variant was present in diverse haplotypes in Rottweilers, and also in Great Danes, indicating an old origin of this second NAPEPLD variant. The identification of different NAPEPLD variants in dog breeds affected by leukoencephalopathies with heterogeneous pathological features, implicates the NAPEPLD enzyme as important in myelin homeostasis, and suggests a novel candidate gene for myelination disorders in people.

Spinal Cord Compression in a Horse due to a Granular Cell Variant of Neurofibroma.

A neurofibroma of granular cell subtype is described in a 7-year-old horse. The horse had a 3-month history of ataxia affecting the forelimbs and hindlimbs, suggesting a C1-C6 neuroanatomical localization. Post-mortem examination revealed an intradural mass arising from the right sixth cervical spinal nerve and compressing the spinal cord. Histologically, the mass was composed largely of wavy spindle cells (a mixture of Schwann cells, perineurial cells and fibroblasts) intimately associated with ropy collagen fibres. Approximately 25% of the spindle cells were swollen and contained densely-packed, eosinophilic and periodic acid-Schiff-positive cytoplasmic granules. Immunohistochemistry for S100 and glial fibrillary acidic protein antigens labelled a proportion of neoplastic cells, while the cytoplasmic granules were positive for S100 and neuron specific enolase. This is the first report of a neurofibroma with granular cell differentiation in an animal. Granular cell differentiation in other peripheral nerve sheath tumours of animals is briefly discussed.

Prevalence of FoxP3(+) Cells in Canine Tumours and Lymph Nodes Correlates Positively with Glucose Transporter 1 Expression.

Hypoxia and regulatory T cells (Tregs) in tumours are both known to be negative prognostic factors in cancer, and this study demonstrated a correlation between the two factors in canine neoplasia. Samples of 57 canine tumours and 29 canine lymph nodes categorized as tumour-draining, with or without metastasis, or reactive and not tumour-associated, were examined. Sequential sections were labelled by immunohistochemistry for glucose transporter 1 (Glut1) and FoxP3 as markers of hypoxia and Tregs, respectively. Up to 21 regions of interest (ROI) were selected in each section in a representative pattern and were assigned a semiquantitative score based on Glut1 labelling. The number of FoxP3(+) cells within each ROI was counted. A generalized estimating equation with negative binomial log link function was used to determine an association between Glut1 expression and FoxP3(+) cell count. Higher Glut1 immunoreactivity was correlated with significantly higher numbers of FoxP3(+) cells in the total tumour sample pool and total lymph node sample pool. Analysis of various subcategories of tumours and lymph nodes showed that this correlation was also present within samples characterized as malignant, haemopoietic mesenchymal tumours, non-haemopoietic mesenchymal tumours, epithelial tumours, lymphoma, lymph nodes containing metastases and reactive lymph nodes. These results indicate that hypoxia in canine tumours may result in an increased infiltration by Tregs.

A Perspective on Veterinary Forensic Pathology and Medicine in the United Kingdom.

Internationally, forensic medicine and pathology are increasingly recognized as an important aspect of work done by veterinary clinicians and veterinary pathologists. In this article, a forensic veterinary clinician, a forensic veterinary pathologist in private practice, and a forensic veterinary pathologist at a veterinary school discuss the interactions among veterinary clinicians, veterinary pathologists, and law enforcement agencies and how future interactions can be improved. The focus is on the United Kingdom, but many of the principles, challenges, and suggestions are applicable to other jurisdictions. Clinicians and pathologists require forensic training to enable them to apply their veterinary knowledge to suspected cases of animal abuse and to subsequently present their findings and conclusions to a court of law in a concise, professional, and unbiased manner, and some opportunities for such advanced training in the United Kingdom are indicated. It is important that forensic veterinary clinicians and pathologists interact in an unbiased and collegial manner to answer the questions posed by courts of law. Opportunities for improved training, communication, and interaction among forensic veterinarians, forensic scientists, and law enforcement are discussed.

Cellular differentiation and proliferation in the ovine lung during gestation and early postnatal development.

This study investigates epithelial cell differentiation and proliferation in specific anatomical regions of the ovine lung during prenatal and postnatal development. Immunohistochemistry was used to identify ciliated epithelial cells, Clara cells, neuroepithelial bodies and type II pneumocytes in the lungs of preterm (67, 127 and 140 days of gestation), full-term (147 days) and postnatal (9, 16 and 91 days old) lambs. Differentiation of ciliated epithelial cells was seen at 67 days of gestation and at term for Clara cells. Neuroepithelial bodies were first detected at 127 days of gestation. From 16 to 91 days of age there was a significant (P <0.05) increase in beta-tubulin (present in ciliated epithelial cells) and Clara cell protein (present in Clara cells) in multiple regions of the lung. Detection of Ki67, a marker of proliferation, in preterm lambs showed a reduction in proliferation index in multiple anatomical regions of the lung between 70 days of gestation and term. Cell proliferation increased following parturition, and then decreased between 16 and 91 days of age, with the largest reduction occurring in the alveolar compartment. Knowledge of which cells are present at specific times of lung development provides valuable information on the anatomy of the ovine lung, improving its use as a model for ovine and human neonatal disease. In addition, the antibodies used here will be valuable for future studies requiring the identification and quantification of respiratory epithelial cell phenotypes in the sheep lung.

Mortality, hepatopathy and liver copper concentrations in artificially reared Jersey calves before and after reductions in copper supplementation.

High winter mortality (28 per cent) in female Jersey calves (80 IU/l in healthy females aged 3-24 weeks, and correlated with serum aspartate transaminase (AST). Copper supplementation of total mixed rations during lactation was excessive (40-60 mg added Cu/kg DM) and reduced to 16-28 mg Cu/kg, but supplementation of milk replacer and creep feed (10 and 35 mg added Cu/kg DM, respectively) continued. The syndrome recurred two years later, and liver Cu remained high in casualties (13.6 ± 2.6) and culled cows (6.38 ± 2.38 mmol/kg DM) prompting withdrawal of all Cu supplements. Mortality remained low (6-9 per cent) thereafter. Three years after removal of all Cu supplements, six culled newborn were examined postmortem; five had normal liver Cu (4.5 ± 1.73), but a sixth had 11.65 mmol/kg DM. In live, healthy calves (1-6 months old) sampled at the same time, GLDH and AST increased with age to levels found five years earlier, indicating possible subclinical hepatopathy. Causative links between Cu supplementation, high calf mortality and hepatopathy are plausible, and reductions in Cu supplementation may prove beneficial in other dairy herds.

Pathology and pathogenesis of ovine pulmonary adenocarcinoma.

Ovine pulmonary adenocarcinoma (OPA), also known as jaagsiekte, is a transmissible lung tumour of sheep caused by jaagsiekte sheep retrovirus (JSRV). JSRV induces neoplastic transformation of alveolar and bronchiolar secretory epithelial cells and the resulting tumours can grow to occupy a significant portion of the lung. Tumour growth is frequently accompanied by the overproduction of fluid in the lung, which further compromises normal respiration. The period between infection and the appearance of clinical signs may be several months or years and many JSRV-infected sheep do not exhibit clinical signs at all during their lifespan. This allows the spread of OPA into new flocks through contact with infected but apparently normal animals. OPA was first described in the early 19th century; however, it has still not been possible to devise effective methods for controlling its spread and it remains an important problem in most countries where sheep are farmed. This is due in part to the absence of an immunological response to JSRV in infected animals, which has hindered the development of serological diagnostic tests and vaccines. In addition to its veterinary importance, OPA is regarded as a potential large animal model for human lung adenocarcinoma and this has stimulated research into the pathogenesis of the ovine disease. This work has produced some significant results, including the finding that one of the JSRV structural proteins is directly involved in oncogenesis. The recent advances in understanding JSRV and the pathogenesis of OPA should lead to novel strategies for diagnosis and control of this disease and for its exploitation as a comparative model for human lung cancer.

Pathology of gastritis and gastric ulceration in the horse. Part 1: range of lesions present in 21 mature individuals.

REASONS FOR PERFORMING STUDY: Gastric ulceration is now widely recognised as an important disease in high performance horses. Little is known about gastric histopathology in healthy or diseased animals; a comprehensive assessment would enhance interpretation of gross findings through assessment of their accuracy and allow for identification of lesion variety and pathogenesis in different anatomical regions of the stomach. OBJECTIVES: To investigate the true extent and variety of gastric lesions in a mixed population of mature horses at post mortem. METHODS: Stomachs were removed from a mixed population of 21 horses at post mortem. Mucosal abnormalities were recorded in photographic and written form. Representative samples from all gross lesions were taken for histopathology and processed routinely. Special stains including Gram, PAS and Warthin Starry, were used when appropriate. Pathological classification of lesion type using both gross and histological appearances was performed. RESULTS: Classification of lesions within the squamous region included hyperkeratosis, punctate scars, diffuse erosions/ ulcerations and margo injuria; and within the glandular region, hyperaemia, focal erosions and ulcerations. Glandular metaplasia was recognised for the first time in the equine stomach. No Helicobacter-like organisms were detected in association with lesion development. CONCLUSIONS AND POTENTIAL RELEVANCE: This study used gross and histological examination to highlight the large variety of naturally occurring gastric lesions in a mixed population of horses. Analysis of the pathogenesis of lesion development is now possible. Further research regarding the range of pathology in larger, more diverse groups of horses is required.

Pathology of gastritis and gastric ulceration in the horse. Part 2: a scoring system.

REASONS FOR PERFORMING STUDY: High numbers of racehorses in training are reported to have gastric ulceration. Gross lesion scoring systems exist, but there is no fixed protocol with which to record gastric microscopic findings. In man, the histological classification of stomach lesions helps in the identification of recognised and emerging aetiologies of gastric disease and aids accurate comparison of findings between studies. In horses, the development of such a system would therefore be of benefit. OBJECTIVES: To develop a pathological scoring system that can be applied to examine samples of the equine stomach at biopsy and post mortem. METHODS AND RESULTS: The equine gastritis grading (EGG) system was developed initially using horse stomachs at post mortem. The protocol involved sampling tissue from 5 fixed locations within the squamous and glandular regions. Histological examination recorded both type and degree of inflammatory infiltrate and the presence of erosions, ulceration or any other reactive change in each slide. These results were combined and an overall diagnosis of gastritis type given for each stomach. CONCLUSIONS AND POTENTIAL RELEVANCE: This is the first example of a complete pathological scoring system developed specifically for recording gastric lesions in the horse. It provides a thorough and repeatable method with which to examine the equine stomach in microscopic detail. It can be used in diagnostic or research situations and the consistency of the information gathered will enable accurate comparison of data between different studies. It aims to give an indication as to the currently undetermined pathological variations seen in the stomach of healthy and diseased horses, as well as increasing the understanding of the pathogenesis of gastritis and gastric ulceration. Using this information, interpretation of biopsy samples is improved.

Dynamic tracheal collapse associated with disseminated histiocytic sarcoma in a cat.

This case report describes an unusual presentation of histiocytic sarcoma in a domestic shorthair cat. Initial investigation revealed a haemodynamically insignificant hypertrophic cardiomyopathy, bronchitis and a mild irregularity of the cervical trachea. The cat's disease progressed over a two-week period. Repeat radiography and tracheoscopy revealed a marked dynamic tracheal collapse associated with a raised plaque-like lesion within the cervical trachea. Subsequent post-mortem examination and histopathology revealed disseminated histiocytic sarcoma involving the trachea and kidneys. This is the first reported case of a histiocytic sarcoma involving the trachea in either dogs or cats.

Diagnosis and management of B cell chronic lymphocytic leukaemia in a cat.

A four-year-old, female neutered domestic shorthair cat had a history of chronic intermittent vomiting and lymphocytosis. B cell chronic lymphocytic leukaemia was diagnosed by flow cytometry, which revealed abnormally large numbers of mature B lymphocytes in the peripheral blood. The cat was treated conservatively with antiemetic drugs and remained stable without chemotherapy for over a year.

Idiopathic hepatic veno-occlusive disease causing Budd-Chiari-like syndrome in a cat.

Budd-Chiari-like syndrome (BCLS) is a rare clinical entity characterised by portal hypertension and ascites. This report describes a case of BCLS in a cat due to obstruction at the level of the hepatic veins. The diagnosis was based on the clinical findings and a histopathological assessment of the liver demonstrating perivenular fibrosis around the central and sublobular veins. Although these lesions are similar to those observed in man with BCLS, the aetiology in this case remains unknown.

Effects of a modified dance-based exercise on cardiorespiratory fitness, psychological state and health status of persons with rheumatoid arthritis.

Cardiorespiratory function and exercise tolerance appear very limited in persons with rheumatoid arthritis (RA). Many studies have demonstrated that aerobic exercise training is beneficial to prevent physical deconditioning without inducing adverse effects on an individual's joints and general health. The present study was conducted to demonstrate that a dance-based exercise program is a safe and efficient activity to improve physical fitness and psychological state in persons with RA. A group of 19 persons (mean age, 49.3 +/- 13 yr) participated in a 12-wk exercise program (twice weekly), whereas 10 persons (mean age, 49.4 +/- 12 yr) served as controls. Health status, use of medication, joint pain and swelling, physical fitness, activity of daily living and psychological state were assessed at baseline, after the 12-wk training program and 6 mo after the end of the program. Exercise training induced a mean improvement of 13% in aerobic power, with the highest values reaching 40%. No significant changes were observed in joint status, even though the count of painful joints tended to decrease in the exercise group. Positive changes in depression, anxiety, fatigue and tension were observed after the 12-wk exercise program. These findings provide some evidences in favor of aerobic exercise in individuals with RA. Furthermore, it is of primary interest to note that a weight-bearing activity with limited ground impacts do not provoke short-term adverse effects on joint status. Further studies, however, are required to determine the long-term effect of weight-bearing exercise on the health status of individuals with RA.