Veterinary Pathology

  • Heterobilharzia americana Infection and Congestive Heart Failure in a Llama (Lama glama) 22 aprile 2015
    Corapi, W. V., Eden, K. B., Edwards, J. F., Snowden, K. F.
    The schistosome Heterobilharzia americana infects several mammalian species in the southeastern United States, including horses, but infections have not been reported in camelids. This is a report of H. americana infection in a 6-year-old llama with extensive cardiac pathology and congestive heart failure. Parasite-induced granulomas were widely disseminated and included overwhelming involvement of the lungs and liver. Microscopic lesions in the heart included myofiber degeneration and necrosis, with extensive replacement fibrosis. Polymerase chain reaction amplification and sequencing confirmed the presence of H. americana in the lungs.
  • A Comparison of Biochemical and Histopathologic Staging in Cats With Chronic Kidney Disease 22 aprile 2015
    McLeland, S. M., Cianciolo, R. E., Duncan, C. G., Quimby, J. M.
    Chronic kidney disease (CKD) is prevalent in elderly cats. Frequently, a diagnosis is made in later stages of disease, by which time many renal lesions are irreversible. As such, little headway has been made in identifying an etiology and preventing this common disease. The aim of this study was to evaluate the presence and severity of both reversible and irreversible histopathologic changes in the kidneys of cats at each stage of CKD and, in addition, to determine if lesion prevalence and character were different between stages. A total of 46 cats with CKD were classified according to the International Renal Interest Society (IRIS) as stage I (3 cats), stage II (16 cats), stage III (14 cats), and stage IV (13 cats). Eleven young, nonazotemic and 10 geriatric, nonazotemic cats were included as controls. The severity of tubular degeneration, interstitial inflammation, fibrosis, and glomerulosclerosis was significantly greater in later stages of CKD compared with early stages of disease. Proteinuria was associated with increased severity of tubular degeneration, inflammation, fibrosis, tubular epithelial single-cell necrosis, and decreased normal parenchyma. Presence of hyperplastic arteriolosclerosis, fibrointimal hyperplasia, or other vascular lesions were not found to be significantly different between hypertensive and normotensive cats. The greater prevalence and severity of irreversible lesions in stage III and IV CKD implies that therapeutic interventions should be targeted at earlier stages of disease.
  • Acute Kidney Injury and Chronic Kidney Disease 22 aprile 2015
    Khan, T. M., Khan, K. N. M.
  • Nephronophthisis and Retinal Degeneration in Tmem218-/- Mice: A Novel Mouse Model for Senior-Loken Syndrome? 22 aprile 2015
    Vogel, P., Gelfman, C. M., Issa, T., Payne, B. J., Hansen, G. M., Read, R. W., Jones, C., Pitcher, M. R., Ding, Z.- M., DaCosta, C. M., Shadoan, M. K., Vance, R. B., Powell, D. R.
    Mice deficient in TMEM218 (Tmem218–/– ) were generated as part of an effort to identify and validate pharmaceutically tractable targets for drug development through large-scale phenotypic screening of knockout mice. Routine diagnostics, expression analysis, histopathology, and electroretinogram analyses completed on Tmem218–/– mice identified a previously unknown role for TMEM218 in the development and function of the kidney and eye. The major observed phenotypes in Tmem218–/– mice were progressive cystic kidney disease and retinal degeneration. The renal lesions were characterized by diffuse renal cyst development with tubulointerstitial nephropathy and disruption of tubular basement membranes in essentially normal-sized kidneys. The retinal lesions were characterized by slow-onset loss of photoreceptors, which resulted in reduced electroretinogram responses. These renal and retinal lesions are most similar to those associated with nephronophthisis (NPHP) and retinitis pigmentosa in humans. At least 10% of NPHP cases present with extrarenal conditions, which most often include retinal degeneration. Senior-Løken syndrome is characterized by the concurrent development of autosomal recessive NPHP and retinitis pigmentosa. Since mutations in the known NPHP genes collectively account for only about 30% of NPHP cases, it is possible that TMEM218 could be involved in the development of similar ciliopathies in humans. In reviewing all other reported mouse models of NPHP, we suggest that Tmem218–/– mice could provide a useful model for elucidating the pathogenesis of cilia-associated disease in both the kidney and the retina, as well as in developing and testing novel therapeutic strategies for Senior-Løken syndrome.
  • Epithelial Cell Shedding and Barrier Function: A Matter of Life and Death at the Small Intestinal Villus Tip 22 aprile 2015
    Williams, J. M., Duckworth, C. A., Burkitt, M. D., Watson, A. J. M., Campbell, B. J., Pritchard, D. M.
    The intestinal epithelium is a critical component of the gut barrier. Composed of a single layer of intestinal epithelial cells (IECs) held together by tight junctions, this delicate structure prevents the transfer of harmful microorganisms, antigens, and toxins from the gut lumen into the circulation. The equilibrium between the rate of apoptosis and shedding of senescent epithelial cells at the villus tip, and the generation of new cells in the crypt, is key to maintaining tissue homeostasis. However, in both localized and systemic inflammation, this balance may be disturbed as a result of pathological IEC shedding. Shedding of IECs from the epithelial monolayer may cause transient gaps or microerosions in the epithelial barrier, resulting in increased intestinal permeability. Although pathological IEC shedding has been observed in mouse models of inflammation and human intestinal conditions such as inflammatory bowel disease, understanding of the underlying mechanisms remains limited. This process may also be an important contributor to systemic and intestinal inflammatory diseases and gut barrier dysfunction in domestic animal species. This review aims to summarize current knowledge about intestinal epithelial cell shedding, its significance in gut barrier dysfunction and host-microbial interactions, and where research in this field is directed.
  • Polycystic Kidneys and GM2 Gangliosidosis-Like Disease in Neonatal Springboks (Antidorcas marsupialis) 22 aprile 2015
    Herder, V., Kummrow, M., Leeb, T., Sewell, A. C., Hansmann, F., Lehmbecker, A., Wohlsein, P., Baumgartner, W.
    Clinical, gross, histopathologic, electron microscopic findings and enzymatic analysis of 4 captive, juvenile springboks (Antidorcas marsupialis) showing both polycystic kidneys and a storage disease are described. Springbok offspring (4 of 34; 12%) were affected by either one or both disorders in a German zoo within a period of 5 years (2008–2013). Macroscopic findings included bilaterally severely enlarged kidneys displaying numerous cysts in 4 animals and superior brachygnathism in 2 animals. Histopathologically, kidneys of 4 animals displayed cystic dilation of the renal tubules. In addition, abundant cytoplasmic vacuoles with a diameter ranging from 2 to 10 μm in neurons of the central and peripheral nervous system, hepatocytes, thyroid follicular epithelial cells, pancreatic islets of Langerhans and renal tubular cells were found in 2 springbok neonates indicative of an additional storage disease. Ultrastructurally, round electron-lucent vacuoles, up to 4 μm in diameter, were present in neurons. Enzymatic analysis of liver and kidney tissue of 1 affected springbok revealed a reduced activity of total hexosaminidase (Hex) with relatively increased HexA activity at the same level of total Hex, suggesting a hexosaminidase defect. Pedigree analysis suggested a monogenic autosomal recessive inheritance for both diseases. In summary, related springboks showed 2 different changes resembling both polycystic kidney and a GM2 gangliosidosis similar to the human Sandhoff disease. Whether the simultaneous occurrence of these 2 entities represents an incidental finding or has a genetic link needs to be investigated in future studies.
  • The Origin and Role of Autophagy in the Formation of Cytoplasmic Granules in Canine Lingual Granular Cell Tumors 22 aprile 2015
    Suzuki, S., Uchida, K., Harada, T., Nibe, K., Yamashita, M., Ono, K., Nakayama, H.
    Granular cell tumors (GCTs) are histologically characterized by polygonal neoplastic cells with abundant eosinophilic cytoplasmic granules. In humans, these cells are considered to be derived from Schwann cells, and the cytoplasmic granules are assumed to be autophagosomes or autophagolysosomes. However, the origin and nature of the cytoplasmic granules in canine GCTs have not been well characterized. The present study examined 9 canine lingual GCTs using immunohistochemistry, transmission electron microscopy (TEM), and cell culture and xenotransplantation experiments. In some cases, the tumor cells expressed S100, CD133, and desmin. The cytoplasmic granules were positive for LC3, p62, NBR1, and ubiquitin. TEM revealed autophagosome-like structures in the cytoplasm of the granule-containing cells. The cultured GCT cells were round to spindle shaped and expressed S100, nestin, Melan-A, CD133, LC3, p62, NBR1, and ubiquitin, suggesting that they were of neural crest origin, redifferentiated into melanocytes, and exhibited upregulated autophagy. The xenotransplanted tumors consisted of spindle to polygonal cells. Only a few cells contained cytoplasmic granules, and some had melanin pigments in their cytoplasm. The xenotransplanted cells expressed S100, nestin, Melan-A, and CD133. P62 and ubiquitin were detected, regardless of the presence or absence of cytoplasmic granules, while LC3 and NBR1 were detected only in the neoplastic cells containing cytoplasmic granules. These findings suggest that some xenotransplanted cells redifferentiated into melanocytes and that autophagy was upregulated in the cytoplasmic granule-containing cells. In conclusion, canine lingual GCTs originate from the neural crest and develop cytoplasmic granules via autophagy. In addition, the microenvironment of GCT cells affects their morphology.
  • Neurogenic Cardiomyopathy in Rabbits With Experimentally Induced Rabies 22 aprile 2015
    Kesdangsakonwut, S., Sunden, Y., Yamada, K., Nishizono, A., Sawa, H., Umemura, T.
    Cardiomyopathies have been rarely described in rabbits. Here we report myocardial necrosis of the ventricular wall in rabbits with experimentally induced rabies. Myocardial lesions were found only in rabbits with brain lesions, and the severity of the cardiac lesions was proportional to that of the brain lesions. Neither the frequency nor the cumulative dose of anesthesia was related to the incidence or the severity of the myocardial lesions. The myocardial lesions were characterized by degeneration and/or necrosis of myocardial cells and were accompanied by contraction band necrosis, interstitial fibrosis, and infiltration of inflammatory cells. The brain lesions due to rabies virus infection were most prominent in the cerebral cortex, thalamus, hypothalamus, brainstem, and medulla. Rabies virus antigen was not found in the hearts of any rabbits. Based on these findings, the myocardial lesions were classified as neurogenic cardiomyopathy.
  • Comparative Neuropathology of Ovine Enterotoxemia Produced by Clostridium perfringens Type D Wild-Type Strain CN1020 and Its Genetically Modified Derivatives 22 aprile 2015
    Garcia, J. P., Giannitti, F., Finnie, J. W., Manavis, J., Beingesser, J., Adams, V., Rood, J. I., Uzal, F. A.
    Clostridium perfringens type D causes enterotoxemia in sheep and goats. The disease is mediated by epsilon toxin (ETX), which affects the cerebrovascular endothelium, increasing vascular permeability and leading to cerebral edema. In the present study, we compared the distribution and severity of the cerebrovascular changes induced in lambs by C. perfringens type D strain CN1020, its isogenic etx null mutant, and the ETX-producing complemented mutant. We also applied histochemical and immunohistochemical markers to further characterize the brain lesions induced by ETX. Both ETX-producing strains induced extensive cerebrovascular damage that did not differ significantly between each other in nature, neuroanatomic distribution, or severity. By contrast, lambs inoculated with the etx mutant or sterile, nontoxic culture medium did not develop detectable brain lesions, confirming that the neuropathologic effects observed in these infections are dependent on ETX production. Lambs treated with the wild-type and complemented strains showed perivascular and mural vascular edema, as well as serum albumin extravasation, particularly severe in the cerebral white matter, midbrain, medulla oblongata, and cerebellum. Brains of animals inoculated with the ETX-producing strains showed decreased expression of glial fibrillary acidic protein and increased expression of aquaporin-4 in the end-feet processes of the astrocytes around blood vessels. Early axonal injury was demonstrated with anti–amyloid precursor protein immunohistochemistry. Perivascular accumulation of macrophages/microglia with intracytoplasmic albumin globules was also observed in these animals. This study demonstrates that ETX is responsible for the major cerebrovascular changes in C. perfringens type D–induced disease.
  • Tuberculosis in Elephants–A Reemergent Disease: Diagnostic Dilemmas, the Natural History of Infection, and New Immunological Tools 22 aprile 2015
    Maslow, J. N., Mikota, S. K.
    Tuberculosis (TB) in elephants has been described since ancient times. However, it was not until 1996 when infection with Mycobacterium tuberculosis was identified in a herd of circus elephants that significant research into this disease began. The epidemiology and natural history of TB were unknown in elephants since there had been no comprehensive screening programs, and diagnostic techniques developed for cervidae and bovidae were of unknown value. And, while precepts of test and slaughter were the norm for cattle and deer, this was considered untenable for an endangered species. With no precedent for the treatment of TB in animals, treatment regimens for elephants were extrapolated from human protocols, which guided changes to the Guidelines for the Control of Tuberculosis in Elephants. In the absence of diagnostic testing to confirm cure in elephants, the efficacy of these treatment regimens is only beginning to be understood as treated elephants die and are examined postmortem. However, because of pressures arising from public relations related to elephant husbandry and the added considerations of TB infection in animals (whether real or imagined), sharing of information to aid in research and treatment has been problematic. Here we review the challenges and successes of the diagnosis of tuberculosis in elephants and discuss the natural history of the disease to put the work of Landolfi et al on the immunological response to tuberculosis in elephants in perspective.