Exudative glomerulonephritis associated with acute leptospirosis in dogs.

In the past 20 years in Switzerland, dogs with suspect acute leptospirosis frequently showed severe glomerular changes that had not been previously reported. These features were characterized by abundant extravasated erythrocytes and fewer neutrophils accompanied by marked fibrin exudation into the urinary space that was interpreted as an exudative glomerulonephritis (GN). This retrospective study describes this significant glomerular pathological change and investigates the association with leptospirosis. Tissues from 50 dogs with exudative GN, retrieved from 2 pathology archives in Switzerland were reviewed using hematoxylin and eosin, periodic acid-Schiff, phosphotungstic acid-hematoxylin, and Warthin and Starry stains. Clinical and postmortem data were collected for each case. Immunohistochemistry (IHC) and/or polymerase chain reactions were used as confirmatory tests for leptospirosis. While all 50 cases had clinical and pathological features supporting a diagnosis of leptospirosis, 37 cases were confirmed for the disease. Using a LipL32 antibody in addition to the OMV2177 antibody raised against the lipopolysaccharide of Leptospira interrogans serovar Copenhageni increased the detection rate of Leptospira by IHC in exudative GN from 24% to 62%. Signalment, seasonality, clinical signs, blood results, and pathological changes in dogs with exudative GN were similar to those reported for dogs without GN and confirmed infection by Leptospira spp.. Exudative GN was common among Swiss dogs with leptospirosis where it caused acute severe disease. Leptospirosis should be considered as a cause of this new pathologic feature by the pathologist. The pathogenesis remains unclear, but involvement of a geographic-specific serovar with unique virulence factors is suspected and warrants further investigation

Natural compound Tetrocarcin-A downregulates Junctional Adhesion Molecule-A in conjunction with HER2 and inhibitor of apoptosis proteins and inhibits tumor cell growth.

Overexpression of the tight junction protein Junctional Adhesion Molecule-A (JAM-A) has been linked to aggressive disease in breast and other cancers, but JAM-targeting drugs remain elusive. Screening of a natural compound library identified the antibiotic Tetrocarcin-A as a novel downregulator of JAM-A and human epidermal growth factor receptor-2 (HER2) protein expression in breast cancer cells. Lysosomal inhibition partially rescued the downregulation of JAM-A and HER2 caused by Tetrocarcin-A, and attenuated its cytotoxic activity. Tetrocarcin-A treatment or JAM-A silencing reduced AKT and ERK phosphorylation, inhibited c-FOS phosphorylation at Threonine-232 (its transcriptional regulation site), inhibited nuclear localization of c-FOS, and downregulated expression of the inhibitor of apoptosis proteins (IAP). This was accompanied by Tetrocarcin-A-induced caspase-dependent apoptosis. To begin evaluating the potential clinical relevance of our findings, we extended our studies to other models. Encouragingly, Tetrocarcin-A downregulated JAM-A expression and caused cytotoxicity in primary breast cells and lung cancer stem cells, and inhibited the growth of xenografts in a semi-in vivo model involving invasion across the chicken egg chorioallantoic membrane. Taken together, our data suggest that Tetrocarcin-A warrants future evaluation as a novel cancer therapeutic by virtue of its ability to downregulate JAM-A expression, reduce tumorigenic signaling and induce apoptosis

Integrated analyses of the microbiological, immunological and ontological transitions in the calf ileum during early life

peer reviewedAberdeen Angus calves were sacrificed from immediately post-birth up to 96 days of age (DOA) and ileal samples were collected for microbial, histological and immunological analyses. Firmicutes bacteria were established immediately in the ileum of calves after birth and remained the dominant phyla at all time points from birth until 96 DOA. Temporal shifts in phyla reflected significantly increased Bacteroidetes at birth followed by temporal increases in Actinobacteria abundance over time. At a cellular level, a significant increase in cell density was detected in the ileal villi over time. The innate cell compartment at birth was composed primarily of eosinophils and macrophages with a low proportion of adaptive T lymphocytes; whereas an increase in the relative abundance of T cells (including those in the intra-epithelial layer) was observed over time. The ileal intestinal cells were immunologically competent as assessed by expression levels of genes encoding the inflammasome sensor NLRP3, and inflammatory cytokines IL1A, IL1B and IL33—all of which significantly increased from birth. In contrast, a temporal reduction in genes encoding anti-inflammatory cytokine IL10 was detected from birth. This study provides an integrated baseline of microbiological, histological and immunological data on the immune adaptation of the neonatal ileum to microbial colonisation in calves.Department of Agriculture, Food and the Marine, Irelan

Multiple myeloma in an Amur tiger (Panthera tigris altaica)

The Amur tiger (Panthera tigris altaica) is an endangered tiger subspecies. An adult zoo-bred female was found collapsed, and died despite supportive treatment. Hematology and biochemistry showed pancytopenia and hyperglobulinemia, and serum protein electrophoresis revealed a monoclonal band in the β-globulin region. Necropsy demonstrated hemoabdomen, multifocal lytic bone marrow lesions, splenomegaly, and hemorrhagic hepatic nodules, with left medial lobe rupture. There were mutifocal hemorrhages in the subcutis, lung, epicardium, and intestinal mucosa. Histopathology demonstrated plasmacytoid cells infiltrating the bone marrow, liver and spleen, and circulating within blood vessels. On immunohistochemistry, cell infiltrates of the three tissues were positive for λ light chains, bone marrow infiltrates were positive for MUM-1 and bone marrow and spleen infiltrates were positive for CD20. These findings indicate that this animal died of hemoabdomen subsequent to multiple myeloma. This is the first time this disease has been reported in a tiger.Health Service Executiv

Multiple myeloma in an Amur tiger (Panthera tigris altaica)

The Amur tiger (Panthera tigris altaica) is an endangered tiger subspecies. An adult zoo-bred female was found collapsed, and died despite supportive treatment.  Hematology and biochemistry showed pancytopenia and hyperglobulinemia, and serum protein electrophoresis revealed a monoclonal band in the β-globulin region. Necropsy demonstrated hemoabdomen, multifocal lytic bone marrow lesions, splenomegaly, and hemorrhagic hepatic nodules, with left medial lobe rupture. There were mutifocal  hemorrhages in the subcutis, lung, epicardium, and intestinal mucosa. Histopathology demonstrated plasmacytoid cells infiltrating the bone marrow, liver and spleen, and  circulating within blood vessels. On immunohistochemistry, cell infiltrates of the three tissues were positive for λ light chains, bone marrow infiltrates were positive for MUM-1 and bone marrow and spleen infiltrates were positive for CD20. These findings indicate that this animal died of hemoabdomen subsequent to multiple myeloma. This is the first time this disease has been reported in a tiger.Keywords: Amur tiger, Immunohistochemistry, Multiple myeloma, Panthera tigris altaica, Serum protein electrophoresis

Multiple myeloma in an Amur tiger (Panthera tigris altaica)

The Amur tiger (Panthera tigris altaica) is an endangered tiger subspecies. An adult zoo-bred female was found collapsed, and died despite supportive treatment. Hematology and biochemistry showed pancytopenia and hyperglobulinemia, and serum protein electrophoresis revealed a monoclonal band in the β-globulin region. Necropsy demonstrated hemoabdomen, multifocal lytic bone marrow lesions, splenomegaly, and hemorrhagic hepatic nodules, with left medial lobe rupture. There were mutifocal hemorrhages in the subcutis, lung, epicardium, and intestinal mucosa. Histopathology demonstrated plasmacytoid cells infiltrating the bone marrow, liver and spleen, and circulating within blood vessels. On immunohistochemistry, cell infiltrates of the three tissues were positive for λ light chains, bone marrow infiltrates were positive for MUM-1 and bone marrow and spleen infiltrates were positive for CD20. These findings indicate that this animal died of hemoabdomen subsequent to multiple myeloma. This is the first time this disease has been reported in a tiger

Occipital condylar dysplasia in a Jacob lamb (Ovis aries)

Jacob sheep (Ovis aries) are a pedigree breed known for their “polycerate” (multihorned) phenotype. We describe a four-horned Jacob lamb that exhibited progressive congenital hindlimb ataxia and paresis, and was euthanased four weeks post-partum. Necropsy and CT-scan revealed deformity and asymmetry of the occipital condyles, causing narrowing of the foramen magnum and spinal cord compression. Histopathology demonstrated Wallerian degeneration of the cervical spinal cord at the level of the foramen magnum. These findings are consistent with occipital condylar dysplasia. This condition has been infrequently reported in the literature as a suspected heritable disease of polycerate Jacob sheep in the USA, and is assumed to arise during selection for the polycerate trait. This is the first reported case in European-bred Jacob sheep. Occipital condylar dysplasia should be considered as a differential diagnosis in polycerate Jacob lambs showing ataxia. It is important to raise awareness of this disease due to its suspected heritability and link to the popular polycerate trait.Keywords: Ataxia, Congenital, Jacob sheep, Occipital condylar dysplasia, Polycerat

Occipital condylar dysplasia in a jacob lamb (Ovis aries)

Jacob sheep (Ovis aries) are a pedigree breed known for their “polycerate” (multihorned) phenotype. We describe a four-horned Jacob lamb that exhibited progressive congenital hindlimb ataxia and paresis, and was euthanased four weeks post-partum. Necropsy and CT-scan revealed deformity and asymmetry of the occipital condyles, causing narrowing of the foramen magnum and spinal cord compression. Histopathology demonstrated Wallerian degeneration of the cervical spinal cord at the level of the foramen magnum. These findings are consistent with occipital condylar dysplasia. This condition has been infrequently reported in the literature as a suspected heritable disease of polycerate Jacob sheep in the USA, and is assumed to arise during selection for the polycerate trait. This is the first reported case in European-bred Jacob sheep. Occipital condylar dysplasia should be considered as a differential diagnosis in polycerate Jacob lambs showing ataxia. It is important to raise awareness of this disease due to its suspected heritability and link to the popular polycerate trait

Non-functional thyroid cystadenoma in three boxer dogs

Background: Thyroid neoplasia is a common endocrine neoplasm in dogs. The boxer is one of the reported breeds predisposed to malignant thyroid neoplasia. However, the association between thyroid neoplasia, malignancy and breed should be considered with caution. Cases presentation: This article describes the presentation, clinical pathological findings, computed tomographic (CT) imaging findings and histopathological features of benign cystic thyroid tumour (cystadenoma) diagnosed in three boxers. These three dogs were presented for investigation of unilateral (n = 2) or bilateral (n = 1) cervical masses with no associated clinical signs of thyroid dysfunction. In each case, post-contrast CT scan identified a large, lateralised, non-invasive, well-defined homogeneous cystic structure with a hyperattenuating contrast-enhancing capsule of suspected thyroid origin displacing the surrounding cervical tissues. Ultrasound-guided fine needle aspiration of the cysts yielded fluid with a high thyroxine concentration in each case. Histopathology was consistent with thyroid cystadenoma in all cases. One dog was concurrently diagnosed with oral melanoma and euthanased. Two dogs underwent surgical excision with one lost to follow-up after 36 months and the other euthanased after 16 months following diagnosis of mast cell tumour. Conclusions: To the authors' knowledge, this is the first detailed report of non-functional benign thyroid cystadenoma in dogs and provides relevant information about case management for this type of tumour. The presence of a large cystic structure associated with benign non-functional thyroid neoplasia may be a condition to which boxer dogs are predisposed