A  B  C  D  E  F  G  H  I  J  K  L  M  N  O  P  Q  R  S  T  U  V  W  X  Y  Z  

  First | 1 2        [Sort by number of followers]   [Restore default list]

  Subjects -> VETERINARY SCIENCE (Total: 225 journals)
Showing 201 - 63 of 63 Journals sorted alphabetically
Veterinary Nurse     Full-text available via subscription   (Followers: 8)
Veterinary Nursing Journal     Hybrid Journal   (Followers: 5)
Veterinary Ophthalmology     Hybrid Journal   (Followers: 9)
Veterinary Parasitology     Hybrid Journal   (Followers: 6)
Veterinary Parasitology : Regional Studies and Reports     Full-text available via subscription  
Veterinary Parasitology : X     Open Access  
Veterinary Pathology     Hybrid Journal   (Followers: 16)
Veterinary Quarterly     Open Access   (Followers: 1)
Veterinary Radiology & Ultrasound     Hybrid Journal   (Followers: 13)
Veterinary Record     Hybrid Journal   (Followers: 26)
Veterinary Research     Open Access   (Followers: 10)
Veterinary Research Communications     Hybrid Journal   (Followers: 1)
Veterinary Science Development     Open Access   (Followers: 1)
Veterinary Sciences     Open Access   (Followers: 3)
Veterinary Surgery     Hybrid Journal   (Followers: 25)
Wartazoa. Indonesian Bulletin of Animal and Veterinary Sciences     Open Access  
Zeitschrift für Ganzheitliche Tiermedizin     Hybrid Journal  
Zoonoses and Public Health     Hybrid Journal   (Followers: 4)

  First | 1 2        [Sort by number of followers]   [Restore default list]

Similar Journals
Journal Cover
Veterinary Pathology
Journal Prestige (SJR): 1.078
Citation Impact (citeScore): 2
Number of Followers: 16  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 0300-9858 - ISSN (Online) 1544-2217
Published by Sage Publications Homepage  [1174 journals]
  • Image Challenge in Veterinary Pathology: Questions

    • Free pre-print version: Loading...

      Pages: 181 - 181
      Abstract: Veterinary Pathology, Volume 59, Issue 2, Page 181-181, March 2022.

      Citation: Veterinary Pathology
      PubDate: 2022-03-16T05:36:32Z
      DOI: 10.1177/03009858211057911
      Issue No: Vol. 59, No. 2 (2022)
       
  • Image Challenge in Veterinary Pathology: Answers: Avian Diseases

    • Free pre-print version: Loading...

      Pages: 386 - 387
      Abstract: Veterinary Pathology, Volume 59, Issue 2, Page 386-387, March 2022.

      Citation: Veterinary Pathology
      PubDate: 2022-03-16T05:36:33Z
      DOI: 10.1177/03009858211057910
      Issue No: Vol. 59, No. 2 (2022)
       
  • Reduced SARS-CoV-2 disease outcomes in Syrian hamsters receiving immune
           sera: Quantitative image analysis in pathologic assessments

    • Free pre-print version: Loading...

      Authors: Cesar Piedra-Mora, Sally R. Robinson, Lisa H. Tostanoski, Denise A. E. Dayao, Abishek Chandrashekar, Katherine Bauer, Linda Wrijil, Sarah Ducat, Tammy Hayes, Jingyou Yu, Esther A. Bondzie, Katherine McMahan, Daniel Sellers, Victoria Giffin, David Hope, Felix Nampanya, Noe B. Mercado, Swagata Kar, Hanne Andersen, Saul Tzipori, Dan H. Barouch, Amanda J. Martinot
      Abstract: Veterinary Pathology, Ahead of Print.
      There is a need to standardize pathologic endpoints in animal models of SARS-CoV-2 infection to help benchmark study quality, improve cross-institutional comparison of data, and assess therapeutic efficacy so that potential drugs and vaccines for SARS-CoV-2 can rapidly advance. The Syrian hamster model is a tractable small animal model for COVID-19 that models clinical disease in humans. Using the hamster model, the authors used traditional pathologic assessment with quantitative image analysis to assess disease outcomes in hamsters administered polyclonal immune sera from previously challenged rhesus macaques. The authors then used quantitative image analysis to assess pathologic endpoints across studies performed at different institutions using different tissue processing protocols. The authors detail pathological features of SARS-CoV-2 infection longitudinally and use immunohistochemistry to quantify myeloid cells and T lymphocyte infiltrates during SARS-CoV-2 infection. High-dose immune sera protected hamsters from weight loss and diminished viral replication in tissues and reduced lung lesions. Cumulative pathology scoring correlated with weight loss and was robust in distinguishing IgG efficacy. In formalin-infused lungs, quantitative measurement of percent area affected also correlated with weight loss but was less robust in non-formalin-infused lungs. Longitudinal immunohistochemical assessment of interstitial macrophage infiltrates showed that peak infiltration corresponded to weight loss, yet quantitative assessment of macrophage, neutrophil, and CD3+ T lymphocyte numbers did not distinguish IgG treatment effects. Here, the authors show that quantitative image analysis was a useful adjunct tool for assessing SARS-CoV-2 treatment outcomes in the hamster model.
      Citation: Veterinary Pathology
      PubDate: 2022-05-06T10:34:10Z
      DOI: 10.1177/03009858221095794
       
  • An outbreak of systemic chlamydiosis in farmed American alligators
           (Alligator mississippiensis)

    • Free pre-print version: Loading...

      Authors: Mariano Carossino, Javier G. Nevarez, Kanako Sakaguchi, Daniel B. Paulsen, Ingeborg M. Langohr, Keith Strother, Jacqueline Ferracone, Alma Roy, Nicholas A. Crossland, Fabio Del Piero
      Abstract: Veterinary Pathology, Ahead of Print.
      Chlamydia spp are reported to causes systemic disease in a variety of hosts worldwide including few reports in crocodilians. Disease presentations vary from asymptomatic to fulminant disease, some of which are zoonotic. The aim of this study was to describe the pathological, immunohistochemical, and molecular findings associated with the occurrence of a previously unreported Chlamydia sp infection causing a major mortality event in farmed American alligators (Alligator mississippiensis). The outbreak presented with sudden death in juvenile alligators mainly associated with necrotizing hepatitis and myocarditis, followed by the occurrence of conjunctivitis after the initial high mortality event. The widespread inflammatory lesions in multiple organs correlated with intralesional chlamydial organisms identified via immunohistochemistry and confirmed by 23S rRNA-specific real-time quantitative polymerase chain reaction (qPCR) for Chlamydiaceae bacteria. By sequencing and phylogenetic analysis of the OmpA gene, this uncultured Chlamydia sp grouped closely with Chlamydia poikilothermis recently described in snakes. This study highlights the significance of such outbreaks in farmed populations. Enhanced epidemiological monitoring is needed to gain further insight into the biology of Chlamydia sp in alligators, disease dynamics, risk factors, and role of carrier animals.
      Citation: Veterinary Pathology
      PubDate: 2022-05-03T10:53:43Z
      DOI: 10.1177/03009858221095269
       
  • Alveolar macrophages protect mice from MERS-CoV-induced pneumonia and
           severe disease

    • Free pre-print version: Loading...

      Authors: Rudragouda Channappanavar, Muneeswaran Selvaraj, Sunil More, Stanley Perlman
      Abstract: Veterinary Pathology, Ahead of Print.
      Emerging and re-emerging human coronaviruses (hCoVs) cause severe respiratory illness in humans, but the basis for lethal pneumonia in these diseases is not well understood. Alveolar macrophages (AMs) are key orchestrators of host antiviral defense and tissue tolerance during a variety of respiratory infections, and AM dysfunction is associated with severe COVID-19. In this study, using a mouse model of Middle East respiratory syndrome coronavirus (MERS-CoV) infection, we examined the role of AMs in MERS pathogenesis. Our results show that depletion of AMs using clodronate (CL) liposomes significantly increased morbidity and mortality in human dipeptidyl peptidase 4 knock-in (hDPP4-KI) mice. Detailed examination of control and AM-depleted lungs at different days postinfection revealed increased neutrophil activity but a significantly reduced MERS-CoV-specific CD4 T-cell response in AM-deficient lungs during later stages of infection. Furthermore, enhanced MERS severity in AM-depleted mice correlated with lung inflammation and lesions. Collectively, these data demonstrate that AMs are critical for the development of an optimal virus-specific T-cell response and controlling excessive inflammation during MERS-CoV infection.
      Citation: Veterinary Pathology
      PubDate: 2022-05-02T12:48:30Z
      DOI: 10.1177/03009858221095270
       
  • Review: NF-kB activation in canine cancer

    • Free pre-print version: Loading...

      Authors: Lisa J. Schlein, Douglas H. Thamm
      Abstract: Veterinary Pathology, Ahead of Print.
      Spontaneous tumors in dogs share several environmental, epidemiologic, biologic, clinical and molecular features with a wide variety of human cancers, making this companion animal an attractive model. Nuclear factor kappa B (NF-kB) transcription factor overactivation is common in several human cancers, and there is evidence that similar signaling aberrations also occur in canine cancers including lymphoma, leukemia, hemangiosarcoma, mammary cancer, melanoma, glioma, and prostate cancer. This review provides an overview of NF-kB signaling biology, both in health and in cancer development. It also summarizes available evidence of aberrant NF-kB signaling in canine cancer, and reviews antineoplastic compounds that have been shown to inhibit NF-kB activity used in various types of canine cancers. Available data suggest that dogs may be an excellent model for human cancers that have overactivation of NF-kB.
      Citation: Veterinary Pathology
      PubDate: 2022-04-30T10:05:51Z
      DOI: 10.1177/03009858221092017
       
  • Animal models for studying covid-19, prevention, and therapy: Pathology
           and disease phenotypes

    • Free pre-print version: Loading...

      Authors: Shambhunath Choudhary, Isis Kanevsky, Lindsay Tomlinson
      Abstract: Veterinary Pathology, Ahead of Print.
      Translational models have played an important role in the rapid development of safe and effective vaccines and therapeutic agents for the ongoing coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Animal models recapitulating the clinical and underlying pathological manifestations of COVID-19 have been vital for identification and rational design of safe and effective vaccines and therapies. This manuscript provides an overview of commonly used COVID-19 animal models and the pathologic features of SARS-CoV-2 infection in these models in relation to their clinical presentation in humans. Also discussed are considerations for selecting appropriate animal models for infectious diseases such as COVID-19, the host determinants that can influence species-specific susceptibility to SARS-CoV-2, and the pathogenesis of COVID-19. Finally, the limitations of currently available COVID-19 animal models are highlighted.
      Citation: Veterinary Pathology
      PubDate: 2022-04-22T10:28:20Z
      DOI: 10.1177/03009858221092015
       
  • Epitheliosis is a histopathological finding associated with malignancy and
           poor prognosis in dogs with mammary tumors

    • Free pre-print version: Loading...

      Authors: Guillermo Valdivia, Ángela Alonso-Diez, Daniel Alonso-Miguel, María Suárez, Paloma García, Gustavo Ortiz-Díez, Maria Dolores Pérez-Alenza, Laura Peña
      Abstract: Veterinary Pathology, Ahead of Print.
      Canine mammary epitheliosis (ME) is a poorly studied dysplasia that may have premalignant potential. In this study, the clinicopathological relevance of ME was prospectively studied in 90 female dogs with mammary tumors (MTs) that underwent radical mastectomy. ME distribution, extent, and coexistence with benign and malignant MTs were evaluated for each case (505 mammary glands). ME was macroscopically undetectable and was present in 47/90 (52%) cases, frequently bilateral. In dogs with malignant MTs and ME, diffuse ME throughout the mammary chain was present in 10/39 (26%) cases. A histological ME-carcinoma transition was evident in certain histotypes. By immunohistochemistry (AE1/AE3, cytokeratin 14 [CK-14], CK-8/18, vimentin, calponin, p63, Ki-67, estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2), ME was a slow-growing, triple-negative process with a strong predominance of basal-like nonmyoepithelial cells. ME was associated with older dogs (P = .016), malignant tumors (P = .044), worse clinical stages (P = .013), lymph node metastasis (LNM, P = .021), higher histological grade tumors (P = .035), and shorter overall survival (OS) in univariate analysis (P = .012). Interestingly, ME was distantly located to the malignant tumor in most cases (P = .007). In multivariate analyses, LNM (P = .005), histological grade (P = .006), and tumor size (P = .006) were independent predictors of OS. For the pathologist, the observation of ME should be clearly stated in the MT biopsy report to alert the surgeon/oncologist. Given the differences between canine ME and its human histopathological counterpart (atypical ductal hyperplasia), “epitheliosis” should remain the preferred term for the dog.
      Citation: Veterinary Pathology
      PubDate: 2022-04-22T10:26:58Z
      DOI: 10.1177/03009858221092013
       
  • Histochemical staining techniques in Culex pipiens and Drosophila
           melanogaster (Diptera) with a comparison to mammals

    • Free pre-print version: Loading...

      Authors: Katharina M. Gregor, Stefanie C. Becker, Fanny Hellhammer, Kathleen Schön, Wolfgang Baumgärtner, Christina Puff
      Abstract: Veterinary Pathology, Ahead of Print.
      Insects play an important role in ecosystems. Changes in their abundance and biodiversity are of paramount interest, as there has not only been an alarming decline of insects important for ecosystem health throughout the past decades, but also an increase in insects detrimental for biomes. Furthermore, insects pose a threat to modern society as arbovirus-transmitting vectors. Therefore, detailed knowledge of insect staining characteristics could be beneficial as a basis for further studies, whether in the context of species conservation or control of insect pests. Thus, this study compared 14 histochemical stains for their usefulness in insects regarding nervous tissue, connective tissue components, mucins and polysaccharides, mineralization, and microorganisms. The study used formalin-fixed paraffin-embedded tissue sections of mammals (Equus caballus) and 2 dipterans (Culex pipiens biotype molestus, Drosophila melanogaster). Several histochemical stains were suitable for tissue assessment in insects and mammals, in particular for nervous tissue (Bielschowsky silver stain, luxol fast blue–cresyl violet) and polysaccharides (alcian blue, periodic acid–Schiff with and without diastase treatment, toluidine blue). Other stains proved useful for visualization of insect-specific organ characteristics such as Gomori’s reticulin stain for tracheoles in both dipteran species, Heidenhain’s azan for midgut-associated connective tissue, and von Kossa for mineral deposition in Malpighian tubules of C. pipiens biotype molestus. In summary, this study provides comparable insights into histochemical procedures in mammals and insects and their usefulness for histological assessment of C. pipiens biotype molestus and D. melanogaster.
      Citation: Veterinary Pathology
      PubDate: 2022-04-11T07:23:11Z
      DOI: 10.1177/03009858221088786
       
  • A systematic analysis of ultrastructural lesions in the Plasmodium
           coatneyi splenectomized rhesus macaque model of severe malaria

    • Free pre-print version: Loading...

      Authors: Eric D. Lombardini, Gareth D. H. Turner, Arthur E. Brown, Laksanee Inamnuay, Theerayuth Kaewamatawong, Piyanate Sunyakumthorn, David J. P. Ferguson
      Abstract: Veterinary Pathology, Ahead of Print.
      Plasmodium falciparum remains one of the world’s deadliest diseases and with ongoing concerns of evolving drug resistance, there is a need for continued refinement of the Plasmodium coatneyi infection model in macaques to study severe malaria. As such, the systemic ultrastructural lesions associated with P. coatneyi infection in splenectomized rhesus macaques was evaluated in 6 animals. Autopsy samples from multiple areas of the central nervous system (CNS), kidneys, heart, liver, and lungs of all 6 animals were processed for electron microscopy. A systematic analysis of the ultrastructural changes associated with the plasmodium was undertaken by multiple pathologists to ensure consensus. All tissues exhibited marked sequestration of infected red blood cells comprised either of cytoadherence to endothelium or rosette formation, associated with variable degrees of host cell damage in a range of tissues that in severe cases resulted in necrosis. This is the first complete systemic evaluation of ultrastructural tissue lesions in P. coatneyi–infected rhesus macaques, and the findings have important implications evaluating of the use of this model for the study of severe malaria caused by P. falciparum in humans.
      Citation: Veterinary Pathology
      PubDate: 2022-04-11T07:22:06Z
      DOI: 10.1177/03009858221088783
       
  • Longitudinal lymph node step-sectioning for the identification of
           metastatic disease in canine mast cell tumor

    • Free pre-print version: Loading...

      Authors: Silvia Sabattini, Eugenio Faroni, Andrea Renzi, Giulia Ghisoni, Antonella Rigillo, Giuliano Bettini, Arianna Pasquini, Stefano Zanardi, Dina Guerra, Laura Marconato
      Abstract: Veterinary Pathology, Ahead of Print.
      Lymph node (LN) metastasis in canine mast cell tumor (MCT) can affect prognosis and postsurgical treatment recommendations; however, routine histological single-section examination may underestimate the incidence of metastases. This prospective study aimed at determining whether longitudinal step-sectioning of the entire LN allows for a more reliable detection of metastases. Dogs with MCT undergoing resection of the primary tumor and regional lymphadenectomy were enrolled. Formalin-fixed LNs were bisected longitudinally, both halves were embedded in paraffin and histological sections prepared at 200 μm steps. The nodal mast cells were classified according to the Weishaar classification. First-section evaluation (FSE; ie, examination of the first section obtained from the blocks) and whole LN step-section evaluation (SSE) were compared. Fifty-eight LNs were included. The median number of sections per LN was 6 (range, 3–28). FSE with toluidine blue (TB) revealed 27 (47%) nonmetastatic (HN0), 14 (24%) premetastatic (HN1), 9 (15%) early metastatic (HN2), and 8 (14%) overtly metastatic (HN3) LNs. SSE with TB resulted in upgrading the LN status in 2 cases (HN2 to HN3; HN0 to HN1). Evaluation of the first section plus an additional step-section resulted in 100% accuracy. Compared with SSE with TB, the accuracy of FSE with HE was 98% for HN3 LNs and 74% for HN2 LNs. FSE appears to reliably allow for the detection of LN metastasis in MCT, although examination of a further parallel section at a 200 μm step may increase the accuracy. A metachromatic stain is recommended for the identification of early metastases.
      Citation: Veterinary Pathology
      PubDate: 2022-04-11T07:18:32Z
      DOI: 10.1177/03009858221088780
       
  • The pandemic penalty on female researchers in veterinary pathology

    • Free pre-print version: Loading...

      Authors: Chiara Palmieri, Rebecca Dunlop, Rachel E. Allavena
      Abstract: Veterinary Pathology, Ahead of Print.

      Citation: Veterinary Pathology
      PubDate: 2022-04-11T07:16:52Z
      DOI: 10.1177/03009858221087640
       
  • Atypical multiple myeloma in 3 young dogs

    • Free pre-print version: Loading...

      Authors: Ian J. Wachowiak, A Russell Moore, Anne Avery, Forgivemore Magunda, Adam Harris, Hannah Laurence, Christopher M. Fulkerson, Caroline V. Fulkerson, Joanne B. Messick, Natalia J. Strandberg, Stephanie McGrath
      Abstract: Veterinary Pathology, Ahead of Print.
      Three dogs under 12 months old were diagnosed with atypical multiple myeloma (MM), having an aggressive multifocal anaplastic round cell sarcoma in bone marrow, viscera, and/or peripheral blood, which were confirmed by cytology and immunohistochemistry to be of plasma cell origin. The intramedullary sarcomas caused myelophthisis, osteolysis, and hypercalcemia. Complete or free light chain monoclonal gammopathy in the serum and/or urine was demonstrated by protein electrophoresis and immunofixation. The polymerase chain reaction for antigen receptor rearrangement assay performed on 2 cases identified a clonally rearranged immunoglobulin gene. Neoplastic cells lacked expression of CD45, CD3, CD18, CD21, CD34, and MHCII by flow cytometry. Immunohistochemistry revealed MUM1 immunoreactivity of the neoplastic cells. Combining all data, the diagnosis was MM. An aggressive form of MM in young dogs should be a differential diagnosis for patients with an immunoglobulin-productive, B cell-clonal, CD45-negative, MUM1-positive discrete cell neoplasm arising from the bone marrow.
      Citation: Veterinary Pathology
      PubDate: 2022-04-11T07:15:59Z
      DOI: 10.1177/03009858221087637
       
  • Preclinical coronavirus studies and pathology: Challenges of the
           high-containment laboratory

    • Free pre-print version: Loading...

      Authors: Victoria K. Baxter, Stephanie A. Montgomery
      Abstract: Veterinary Pathology, Ahead of Print.
      The COVID-19 pandemic has highlighted the critical role that animal models play in elucidating the pathogenesis of emerging diseases and rapidly analyzing potential medical countermeasures. Relevant pathologic outcomes are paramount in evaluating preclinical models and therapeutic outcomes and require careful advance planning. While there are numerous guidelines for attaining high-quality pathology specimens in routine animal studies, preclinical studies using coronaviruses are often conducted under biosafety level-3 (BSL3) conditions, which pose unique challenges and technical limitations. In such settings, rather than foregoing pathologic outcomes because of the inherent constraints of high-containment laboratory protocols, modifications can be made to conventional best practices of specimen collection. Particularly for those unfamiliar with working in a high-containment laboratory, the authors describe the logistics of conducting such work, focusing on animal experiments in BSL3 conditions. To promote scientific rigor and reproducibility and maximize the value of animal use, the authors provide specific points to be considered before, during, and following a high-containment animal study. The authors provide procedural modifications for attaining good quality pathologic assessment of the mouse lung, central nervous system, and blood specimens under high-containment conditions while being conscientious to maximize animal use for other concurrent assays.
      Citation: Veterinary Pathology
      PubDate: 2022-04-11T07:14:27Z
      DOI: 10.1177/03009858221087634
       
  • Gastrointestinal stromal tumors with Kit gene mutation in 4 guinea pigs
           (Cavia porcellus)

    • Free pre-print version: Loading...

      Authors: Kengo Ueda, Masamine Takanosu, Yumiko Kagawa, Akiko Ueda, Naoko Ano, Kohji Nomura, Kiyokazu Ozaki
      Abstract: Veterinary Pathology, Ahead of Print.
      Gastrointestinal stromal tumors (GISTs) have been rarely reported in guinea pigs. We aimed to characterize the clinical and pathological features of GISTs in 4 guinea pigs and investigate the presence of mutations in exon 11 of the KIT proto-oncogene receptor tyrosine kinase (Kit) gene. Two subjects were male and 2 were female; 2 were 6 years old, 1 was 7 years old, and 1 was of an unknown age. Three cases had primary gastric tumors, whereas 1 had a primary small intestinal tumor. All cases had tumors that extended from the submucosa to the serosa with extraluminal growth. A gastric tumor had gastric, pancreatic, and cecal metastases. Histologically, the tumors were sharply demarcated and composed of spindle cells arranged in bundles, intermixed with small amounts of collagenous stroma. The tumor cells had mild atypia with few mitotic figures (0–5/50 high power fields, 7.95 mm2) and were immunolabeled for KIT and Discovered-on-GIST 1 (DOG1). All cases had mutations in exon 11 of the Kit gene. These findings indicate that GISTs in guinea pigs are similar to those in humans and dogs. GISTs in guinea pigs are potentially malignant submucosal tumors with KIT- and DOG1-immunolabeling, exon 11 KIT mutations, and the possibility of metastasis.
      Citation: Veterinary Pathology
      PubDate: 2022-04-08T09:14:31Z
      DOI: 10.1177/03009858221087630
       
  • Canine and murine models of osteosarcoma

    • Free pre-print version: Loading...

      Authors: Jessica Beck, Ling Ren, Shan Huang, Erika Berger, Kathleen Bardales, Joshua Mannheimer, Christina Mazcko, Amy LeBlanc
      Abstract: Veterinary Pathology, Ahead of Print.
      Osteosarcoma (OS) is the most common malignant bone tumor in children. Despite efforts to develop and implement new therapies, patient outcomes have not measurably improved since the 1980s. Metastasis continues to be the main source of patient mortality, with 30% of cases developing metastatic disease within 5 years of diagnosis. Research models are critical in the advancement of cancer research and include a variety of species. For example, xenograft and patient-derived xenograft (PDX) mouse models provide opportunities to study human tumor cells in vivo while transgenic models have offered significant insight into the molecular mechanisms underlying OS development. A growing recognition of naturally occurring cancers in companion species has led to new insights into how veterinary patients can contribute to studies of cancer biology and drug development. The study of canine cases, including the use of diagnostic tissue archives and clinical trials, offers a potential mechanism to further canine and human cancer research. Advancement in the field of OS research requires continued development and appropriate use of animal models. In this review, animal models of OS are described with a focus on the mouse and tumor-bearing pet dog as parallel and complementary models of human OS.
      Citation: Veterinary Pathology
      PubDate: 2022-03-26T11:11:47Z
      DOI: 10.1177/03009858221083038
       
  • Giraffe skin disease: Clinicopathologic characterization of cutaneous
           filariasis in the critically endangered Nubian giraffe (Giraffa
           camelopardalis camelopardalis)

    • Free pre-print version: Loading...

      Authors: Sushan Han, Liza Dadone, Sara Ferguson, Priya Bapodra-Villaverde, Patricia M. Dennis, Robert Aruho, Miranda J. Sadar, Julian Fennessy, Margaret Driciru, Arthur B. Muneza, Michael B. Brown, Matthew Johnston, Kevin Lahmers
      Abstract: Veterinary Pathology, Ahead of Print.
      Giraffe skin disease (GSD) is an emerging disease of free-ranging giraffe recognized in the last 25 years in several species, including the critically endangered Nubian giraffe (Giraffa camelopardalis camelopardalis) of Uganda. Identifying the cause of GSD and understanding its impact on health were deemed paramount to supporting these vulnerable populations. Sixty-four giraffes were immobilized in Murchison Falls National Park, Uganda, from 2017 to 2019, and GSD lesions were opportunistically biopsied. Fifty-five giraffes (86%) had GSD lesions on the neck, axilla, chest, and cranial trunk. Lesions were categorized into early, intermediary, and dormant stages based on gross and histological characteristics. Early lesions were smaller, crusted nodules with eosinophilic and pyogranulomatous dermatitis and furunculosis. Intermediary lesions were thick plaques of proliferative and fissured hyperkeratosis and acanthosis with dense dermal granulation tissue and severe eosinophilic and granulomatous dermatitis. Lesions appeared to resolve to dormancy, with dormant lesions consisting of hairless plaques of hyperkeratosis with dermal scarring and residual inflammation. The periphery of early and intermediary lesions included follicular granulomas containing adult filarid nematodes, with myriad encysted microfilariae in the superficial dermis. Stage L3 larvae were common in early and intermediary lesions, and dormant lesions had remnant encysted microfilariae with no adult or stage L3 larvae. Nematodes were morphologically and genetically novel with close identity to Stephanofilaria spp. and Brugia malayi, which cause infectious filariasis. Identification of potential insect vectors, long-term monitoring of GSD lesions, and evaluating response to therapy is ongoing in the efforts to help conserve the Nubian giraffe.
      Citation: Veterinary Pathology
      PubDate: 2022-03-21T11:35:43Z
      DOI: 10.1177/03009858221082606
       
  • Pathology of the peripheral neuropathy Charcot-Marie-Tooth disease type 4H
           in Holstein Friesian cattle with a splice site mutation in FGD4

    • Free pre-print version: Loading...

      Authors: Keren E. Dittmer, Catherine Neeley, Matthew R. Perrott, Edwardo Reynolds, Dorian J. Garrick, Mathew D. Littlejohn
      Abstract: Veterinary Pathology, Ahead of Print.
      Charcot-Marie-Tooth disease (CMT) is a hereditary sensory and motor peripheral neuropathy that is one of the most common inherited neurological diseases of humans and may be caused by mutations in a number of different genes. The subtype Charcot-Marie-Tooth disease type 4H (CMT4H) is caused by homozygous mutations in the FGD4 (FYVE, RhoGEF, and PH domain-containing 4) gene. A previous genome-wide association study involving 130,783 dairy cows found 6 novel variants, one of which was a homozygous splice site mutation in the FGD4 gene. Descendants of carriers were genotyped to identify 9 homozygous Holstein Friesian calves that were raised to maturity, of which 5 were euthanized and sampled for histopathology and electron microscopy at 2 and 2.5 years of age. Three control Holstein Friesian animals were raised with the calves and euthanized at the same time points. No macroscopic lesions consistent with CMT4H were seen at necropsy. Microscopically, peripheral nerves were hypercellular due to hyperplasia of S100-positive Schwann cells, and there was onion bulb formation, axonal degeneration with demyelination, and increased thickness of the endoneurium. On electron microscopy, decreased axonal density, onion bulb formations, myelin outfoldings, and increased numbers of mitochondria were present. These changes are consistent with those described in mouse models and humans with CMT4H, making these cattle a potential large animal model for CMT.
      Citation: Veterinary Pathology
      PubDate: 2022-03-18T06:41:09Z
      DOI: 10.1177/03009858221083041
       
  • Neuropathology of feral conures with bromethalin toxicosis

    • Free pre-print version: Loading...

      Authors: Mauricio Seguel, Rita McManamon, Drury Reavill, Fern Van Sant, Sayed M. Hassan, Branson W. Ritchie, Elizabeth W. Howerth
      Abstract: Veterinary Pathology, Ahead of Print.
      Bromethalin is a widely used neurotoxic rodenticide sometimes affecting nontarget wildlife. However, the effects of bromethalin on avian species are largely unknown. Here, we report the neuropathology of 14 feral conures (Psittacara sp.) with bromethalin toxicosis. Clinically, all birds presented with different degrees of paraparesis that sometimes progressed to dysphagia, ataxia, and tetraparesis. Histologically, there was astrogliosis, pallor, and vacuolation of white matter in the brain. This was usually more prominent in the medial longitudinal fasciculus, pons, optic tectum, cerebellar peduncle, and ventral funiculus. In most affected areas, there was loss of oligodendrocytes, and axons had extensive myelin loss or marked intramyelinic edema with splitting of myelin sheaths at the intraperiod line. Conures with bromethalin toxicosis had neuropathological changes similar to those of mammals exposed to bromethalin but with a characteristic distribution, probably related to higher susceptibility to cytotoxic edema in certain regions of the avian brain.
      Citation: Veterinary Pathology
      PubDate: 2022-03-18T06:35:31Z
      DOI: 10.1177/03009858221082300
       
  • The use of alkaline phosphatase and runx2 to distinguish osteosarcoma from
           other common malignant primary bone tumors in dogs

    • Free pre-print version: Loading...

      Authors: Anne Barger, Kate Baker, Elizabeth Driskell, Will Sander, Patrick Roady, Matthew Berry, Amy Schnelle, Timothy M. Fan
      Abstract: Veterinary Pathology, Ahead of Print.
      In dogs, primary bone tumors can be difficult to distinguish with histopathology. Of those tumors, osteosarcoma (OSA) is the most common and aggressive. In this study, 4 immunohistochemistry markers—alkaline phosphatase (ALP), osteonectin (ON), osteopontin (OP), and runx2—were evaluated for their ability to distinguish OSA from other primary bone tumors. The 42 formalin-fixed, paraffin-embedded, primary canine bone tumors included 15 OSAs, 8 chondrosarcomas, 11 fibrosarcomas, and 8 histiocytic sarcomas. All 4 antibodies were highly sensitive for detection of osteosarcoma. ALP was the most sensitive at 100% and runx2 the most specific at 78%. Running ALP and runx2 in series resulted in a sensitivity of 87% and a specificity of 85%. This combination of immunomarkers resulted in a diagnostic panel for distinguishing osteosarcoma from other primary bone tumors.
      Citation: Veterinary Pathology
      PubDate: 2022-03-07T07:24:52Z
      DOI: 10.1177/03009858221083035
       
  • Interstitial pneumonia and diffuse alveolar damage in domestic animals

    • Free pre-print version: Loading...

      Authors: Francisco R. Carvallo, Valentina B. Stevenson
      Abstract: Veterinary Pathology, Ahead of Print.
      Classification of pneumonia in animals has been controversial, and the most problematic pattern is interstitial pneumonia. This is true from the gross and histologic perspectives, and also from a mechanistic point of view. Multiple infectious and noninfectious diseases are associated with interstitial pneumonia, all of them converging in the release of inflammatory mediators that generate local damage and attract inflammatory cells that inevitably trigger a second wave of damage. Diffuse alveolar damage is one of the more frequently identified histologic types of interstitial pneumonia and involves injury to alveolar epithelial and/or endothelial cells, with 3 distinct stages. The first is the “exudative” stage, with alveolar edema and hyaline membranes. The second is the “proliferative” stage, with hyperplasia and reactive atypia of type II pneumocytes, infiltration of lymphocytes, plasma cells, and macrophages in the interstitium and early proliferation of fibroblasts. These stages are reversible and often nonfatal. If damage persists, there is a third “fibrosing” stage, characterized by fibrosis of the interstitium due to proliferation of fibroblasts/myofibroblasts, persistence of type II pneumocytes, segments of squamous metaplasia of alveolar epithelium, plus inflammation. Understanding the lesion patterns associated with interstitial pneumonias, their causes, and the underlying mechanisms aid in accurate diagnosis that involves an interdisciplinary collaborative approach involving pathologists, clinicians, and radiologists.
      Citation: Veterinary Pathology
      PubDate: 2022-03-07T07:22:38Z
      DOI: 10.1177/03009858221082228
       
  • Histopathology and localization of SARS-CoV-2 and its host cell entry
           receptor ACE2 in tissues from naturally infected US-farmed mink (Neovison
           vison)

    • Free pre-print version: Loading...

      Authors: Jana M. Ritter, Tais M. Wilson, Joy M. Gary, Josilene N. Seixas, Roosecelis B. Martines, Julu Bhatnagar, Brigid C. Bollweg, Elizabeth Lee, Lindsey Estetter, Luciana Silva-Flannery, Hannah A. Bullock, Jonathan S. Towner, Caitlin M. Cossaboom, Natalie M. Wendling, Brian R. Amman, Robert R. Harvey, Dean Taylor, Hannah Rettler, Casey Barton Behravesh, Sherif R. Zaki
      Abstract: Veterinary Pathology, Ahead of Print.
      Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes respiratory disease in mink similar to human COVID-19. We characterized the pathological findings in 72 mink from US farms with SARS-CoV-2 outbreaks, localized SARS-CoV-2 and its host cellular receptor angiotensin-converting enzyme 2 (ACE2) in mink respiratory tissues, and evaluated the utility of various test methods and specimens for SARS-CoV-2 detection in necropsy tissues. Of SARS-CoV-2-positive animals found dead, 74% had bronchiolitis and diffuse alveolar damage (DAD). Of euthanized SARS-CoV-2-positive animals, 72% had only mild interstitial pneumonia or minimal nonspecific lung changes (congestion, edema, macrophages); similar findings were seen in SARS-CoV-2-negative animals. Suppurative rhinitis, lymphocytic perivascular inflammation in the lungs, and lymphocytic infiltrates in other tissues were common in both SARS-CoV-2-positive and SARS-CoV-2-negative animals. In formalin-fixed paraffin-embedded (FFPE) upper respiratory tract (URT) specimens, conventional reverse transcription–polymerase chain reaction (cRT-PCR) was more sensitive than in situ hybridization (ISH) or immunohistochemistry (IHC) for detection of SARS-CoV-2. FFPE lung specimens yielded less detection of virus than FFPE URT specimens by all test methods. By IHC and ISH, virus localized extensively to epithelial cells in the nasal turbinates, and prominently within intact epithelium; olfactory mucosa was mostly spared. The SARS-CoV-2 receptor ACE2 was extensively detected by IHC within turbinate epithelium, with decreased detection in lower respiratory tract epithelium and alveolar macrophages. This study expands on the knowledge of the pathology and pathogenesis of natural SARS-CoV-2 infection in mink and supports their further investigation as a potential animal model of SARS-CoV-2 infection in humans.
      Citation: Veterinary Pathology
      PubDate: 2022-03-01T10:03:58Z
      DOI: 10.1177/03009858221079665
       
  • Reporting guidelines for manuscripts on tumor prognosis

    • Free pre-print version: Loading...

      Authors: F. Yvonne Schulman, Paola Roccabianca, Giancarlo Avallone, Christof A. Bertram, Mark Chalkley, James K. Chambers, Taryn A. Donovan, Robert A. Foster, Donald Meuten, Ilaria Porcellato, Simon L. Priestnall, Roberta Rasotto, Kazuyuki Uchida, Joshua D. Webster, Geoffrey A. Wood, Jeff L. Caswell
      Abstract: Veterinary Pathology, Ahead of Print.

      Citation: Veterinary Pathology
      PubDate: 2022-02-26T01:26:45Z
      DOI: 10.1177/03009858221082207
       
  • Macroglossia in a pig diagnosed as Becker muscular dystrophy due to
           dystrophin pseudoexon insertion derived from intron 26

    • Free pre-print version: Loading...

      Authors: Naoyuki Aihara, Sho Kuroki, Ryosuke Inamuro, Yumiko Kamiya, Takanori Shiga, Yoh Kikuchihara, Emiko Ohmori, Michiko Noguchi, Junichi Kamiie
      Abstract: Veterinary Pathology, Ahead of Print.
      We report a case of Becker muscular dystrophy in a 6-month-old, mixed-breed, castrated male pig detected with macroglossia at a meat inspection center. The pig presented a severely enlarged tongue extending outside its mouth. The tongue was firm and pale with discolored muscles. Histologically, there was severe fibrosis, fatty replacement, and myofiber necrosis, degeneration, and regeneration. Immunofluorescence showed focal and severely weak labeling for dystrophin at the sarcolemma of myocytes in the tongue. Analysis of dystrophin mRNA showed a 62 base pair insertion between exons 26 and 27. The insertion was derived from intron 26. Based on these findings, we diagnosed the case as Becker muscular dystrophy—the first known muscular dystrophy case induced by pseudoexon insertion in animals.
      Citation: Veterinary Pathology
      PubDate: 2022-02-26T01:24:52Z
      DOI: 10.1177/03009858221079669
       
  • In situ squamous cell carcinoma of the gingiva and nictitating membrane
           associated with Felis catus papillomavirus type 3 in a cat

    • Free pre-print version: Loading...

      Authors: John S. Munday, Michael Hardcastle, Naomi Dally
      Abstract: Veterinary Pathology, Ahead of Print.
      Oral squamous cell carcinomas (OSCCs) are common cancers of cats. While papillomaviruses (PVs) are an important cause of human OSCCs, there is currently little evidence that PVs cause squamous cell carcinomas (SCCs) of the mouth or other mucosal surfaces in cats. In the present cat, in situ carcinomas developed on the gingiva and nictitating membrane. Neoplastic cells within both cancers contained prominent PV-induced cellular changes consistent with those caused by Felis catus PV3 (FcaPV3), and FcaPV3 DNA was amplified from both cancers. Neoplasms also contained intense nuclear and cytoplasmic p16CDKN2A protein (p16) immunolabeling, suggesting PV-induced degradation of retinoblastoma protein. The molecular and histological features strongly suggested the cancers were caused by FcaPV3 infection. This is the first report of an association between PV infection and the development of an in situ carcinoma of the mucosa of cats. The identification of these lesions suggests that PVs might cause a proportion of OSCCs, and SCCs from other mucosal surfaces, in cats.
      Citation: Veterinary Pathology
      PubDate: 2022-02-26T01:19:29Z
      DOI: 10.1177/03009858221079667
       
  • Sox9, Hopx, and survivin and tuft cell marker DCLK1 expression in normal
           canine intestine and in intestinal adenoma and adenocarcinoma

    • Free pre-print version: Loading...

      Authors: Wencke Reineking, Ida E. Schauerte, Johannes Junginger, Marion Hewicker-Trautwein
      Abstract: Veterinary Pathology, Ahead of Print.
      Self-renewal of the intestinal epithelium originates from stem cells located at the crypt base. Upregulation of various stem cell markers in intestinal epithelial neoplasms indicates a potential role of stem cells in tumorigenesis. In this study, the immunoreactivity of potential intestinal stem cell markers (Sry box transcription factor 9 [Sox9], homeodomain-only protein [Hopx], survivin) and tuft cell marker doublecortin-like kinase 1 (DCLK1) in normal canine intestine and intestinal epithelial neoplasms was investigated. Formalin-fixed paraffin-embedded (FFPE) small and large intestine as well as intestinal neoplasms (55 colorectal adenomas [CRAs], 17 small intestinal adenocarcinomas [SICs], and 12 colorectal adenocarcinomas [CRCs]) were analyzed immunohistologically. Potential stem cell markers Sox9, Hopx, and survivin were detected in the crypts of normal canine small and large intestine. DCLK1+ tuft cells were present in decreasing numbers along the crypt-villus axis of the jejunum and rarely detectable in large intestine. In canine intestinal epithelial tumors, nuclear Sox9 immunoreactivity was detectable in 84.9% (CRA), 80% (CRC), and 77% of epithelial neoplastic cells (SIC). Hopx and survivin were expressed within cytoplasm and nuclei of neoplastic cells in benign and malignant tumors. DCLK1 showed a cytoplasmic reaction within neoplastic cells. The combined score of Hopx, DCLK1, and survivin varied among the examined cases. Overall, malignant tumors showed lower DCLK1 scores but higher Hopx scores in comparison with benign tumors. For survivin, no differences were detectable. In conclusion, stem cell markers Sox9, Hopx, and survivin were detectable at the crypt base and the immunoreactivity of Sox9, DCLK1, survivin, and Hopx was increased in canine intestinal adenomas and adenocarcinomas compared with normal mucosa.
      Citation: Veterinary Pathology
      PubDate: 2022-02-26T01:17:30Z
      DOI: 10.1177/03009858221079666
       
  • Talaromyces spp. infections in dogs from the Southern United States

    • Free pre-print version: Loading...

      Authors: Rebecca L. Bacon, Stephanie A. Lovell, Aline Rodrigues Hoffman, Alycia P. Fratzke
      Abstract: Veterinary Pathology, Ahead of Print.
      Talaromyces spp. are soil-dwelling fungi sporadically reported to cause disease in humans and dogs. This study summarized the clinical presentations, histologic findings, and Talaromyces sp. involved in 5 dogs diagnosed through the panfungal polymerase chain reaction service (PCR) at Texas A&M University, with a review of previously reported cases. Of the 5 cases, 3 were Labrador Retrievers, 2 were male, and 3 were female. Three of 5 involved the musculoskeletal or lymphatic systems, and 2 of 5 dogs presented with meningoencephalitis. Talaromyces helicus, Talaromyces aurantiacus, and Talaromyces boninensis were identified based on panfungal PCR, showing 99% to 100% sequence matches in combination with morphologic features. Three of 5 dogs had static disease at the time of publication, 1 was euthanized, and 1 was lost to follow-up. This study describes Talaromyces spp. as a cause of meningoencephalitis in dogs, identifies 2 novel Talaromyces spp. involved in infections, and adds to the existing knowledge of clinical presentations and outcomes.
      Citation: Veterinary Pathology
      PubDate: 2022-02-09T10:12:02Z
      DOI: 10.1177/03009858221075589
       
  • Perfusion with 10% neutral-buffered formalin is equivalent to 4%
           paraformaldehyde for histopathology and immunohistochemistry in a mouse
           model of experimental autoimmune encephalomyelitis

    • Free pre-print version: Loading...

      Authors: Jessica M. Snyder, Enrico Radaelli, Adam Goeken, Thomas Businga, Alexander W. Boyden, Nitin J. Karandikar, Katherine N. Gibson-Corley
      Abstract: Veterinary Pathology, Ahead of Print.
      Intravascular (IV) perfusion of tissue fixative is commonly used in the field of neuroscience as the central nervous system tissues are exquisitely sensitive to handling and fixation artifacts which can affect downstream microscopic analysis. Both 10% neutral-buffered formalin (NBF) and 4% paraformaldehyde (PFA) are used, although IV perfusion with PFA is most commonly referenced. The study objective was to compare the severity of handling and fixation artifacts, semiquantitative scores of inflammatory and neurodegenerative changes, and quantitative immunohistochemistry following terminal IV perfusion of mice with either 10% NBF or 4% PFA in a model of experimental autoimmune encephalitis (EAE). The study included 24 mice; 12 were control animals not immunized and an additional 12 were immunized with PLP139–151 subcutaneously, harvested at day 20, and fixed in the same fashion. Equal numbers (4 per group) were perfused with 10% NBF or 4% PFA, and 4 were immersion-fixed in 10% NBF. NBF-perfused mice had less severe dark neuron artifact than PFA-perfused mice (P < .001). Immersion-fixed animals had significantly higher scores for oligodendrocyte halos, dark neuron artifact, and perivascular clefts than perfusion-fixed animals. Histopathology scores in EAE mice for inflammation, demyelination, and necrosis did not differ among fixation methods. Also, no significant differences in quantitative immunohistochemistry for CD3 and Iba-1 were observed in immunized animals regardless of the method of fixation. These findings indicate that IV perfusion of mice with 10% NBF and 4% PFA are similar and adequate fixation techniques in this model.
      Citation: Veterinary Pathology
      PubDate: 2022-02-08T07:56:29Z
      DOI: 10.1177/03009858221075588
       
  • Non-thrombotic pulmonary embolism of brain, liver, or bone marrow tissues
           associated with traumatic injuries in free-ranging neotropical primates

    • Free pre-print version: Loading...

      Authors: Ayisa Rodrigues Oliveira, Daniel Oliveira dos Santos, Fabiana Pizzolato de Lucena, Sara Aquino de Mattos, Thaynara Parente de Carvalho, Fabíola Barroso Costa, Larissa Giannini Alves Moreira, Izabela Magalhães Arthuso Vasconcelos, Tatiane Alves da Paixão, Renato Lima Santos
      Abstract: Veterinary Pathology, Ahead of Print.
      From 2016 to 2019, Southeastern Brazil faced an outbreak of yellow fever (YF) affecting both humans and New World primates (NWP). The outbreak was associated with a marked increase in traumatic lesions in NWP in the affected regions. Non-thrombotic pulmonary embolization (NTPE) can be a consequence of massive traumatic events, and it is rarely reported in human and veterinary medicine. Here, we describe NTPE of the brain, liver, and bone marrow in free-ranging NWP, highlighting the epidemiological aspects of these findings and the lesions associated with this condition, including data on traumatic injuries in wild NWP populations during the course of a recent YF outbreak. A total of 1078 NWP were necropsied from January 2017 to July 2019. Gross traumatic injuries were observed in 444 marmosets (44.3%), 10 howler monkeys (23.2%), 9 capuchins (31.0%), 1 titi-monkey (50.0%), and 1 golden lion tamarin (33.3%). NTPE was observed in 10 animals, including 9 marmosets (2.0%) and 1 howler monkey (10.0%). NTPE was identified in the lung and comprised hepatic tissue in 1 case, brain tissue in 1 case, and bone marrow tissue in 8 cases. Although uncommon, it is important to consider NTPE with pulmonary vascular occlusion during the critical care of traumatized NWP. In addition, this study highlights the importance of conservational strategies and environmental education focusing on One Health, not only to protect these free-ranging NWP populations but also to maintain the efficacy of epidemiological surveillance programs.
      Citation: Veterinary Pathology
      PubDate: 2022-02-08T07:54:18Z
      DOI: 10.1177/03009858221075595
       
  • Dysplastic gangliocytoma of the cerebellum in a cat

    • Free pre-print version: Loading...

      Authors: Michelle Imlau, Mamoun Saeed, Jane Cryan, Seamus Hoey, Myles McKenna, Hanne Jahns, Pamela Kelly
      Abstract: Veterinary Pathology, Ahead of Print.
      A 2.5-year-old cat presented with progressive ataxia and lethargy. Magnetic resonance imaging (MRI) showed enlargement of the cerebellum and herniation of cerebellar vermis. Postmortem examination confirmed the MRI findings, and histopathology showed numerous large dysplastic neurons populating and displacing the Purkinje cell layer and extending into the molecular and granular layers of the cerebellum. The lesion was diagnosed as dysplastic gangliocytoma of the cerebellum. In humans, this tumor is often associated with Cowden syndrome, a genetic disorder characterized by multiple hamartomas and an increased risk of developing certain neoplasms, known to be linked to a germline mutation of the phosphatase and tensin homolog (PTEN) gene. Reduction in PTEN nuclear and cytoplasmic immunohistochemical labeling of dysplastic neurons in this case suggested a possible PTEN mutation involved in the tumorigenesis. This report provides a detailed pathology description of the tumor and the use of neuronal and PTEN markers which will help guide pathologists presented with this rare condition in the future.
      Citation: Veterinary Pathology
      PubDate: 2022-02-08T07:50:18Z
      DOI: 10.1177/03009858221075594
       
  • Alternatives to animal models and their application in the discovery of
           species susceptibility to SARS-CoV-2 and other respiratory infectious
           pathogens: A review

    • Free pre-print version: Loading...

      Authors: Sandra Runft, Iris Färber, Johannes Krüger, Nadine Krüger, Federico Armando, Cheila Rocha, Stefan Pöhlmann, Laura Burigk, Eva Leitzen, Malgorzata Ciurkiewicz, Armin Braun, Daniel Schneider, Lars Baumgärtner, Bernd Freisleben, Wolfgang Baumgärtner
      Abstract: Veterinary Pathology, Ahead of Print.
      The emergence of the coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inspired rapid research efforts targeting the host range, pathogenesis and transmission mechanisms, and the development of antiviral strategies. Genetically modified mice, rhesus macaques, ferrets, and Syrian golden hamsters have been frequently used in studies of pathogenesis and efficacy of antiviral compounds and vaccines. However, alternatives to in vivo experiments, such as immortalized cell lines, primary respiratory epithelial cells cultured at an air–liquid interface, stem/progenitor cell-derived organoids, or tissue explants, have also been used for isolation of SARS-CoV-2, investigation of cytopathic effects, and pathogen–host interactions. Moreover, initial proof-of-concept studies for testing therapeutic agents can be performed with these tools, showing that animal-sparing cell culture methods could significantly reduce the need for animal models in the future, following the 3R principles of replace, reduce, and refine. So far, only few studies using animal-derived primary cells or tissues have been conducted in SARS-CoV-2 research, although natural infection has been shown to occur in several animal species. Therefore, the need for in-depth investigations on possible interspecies transmission routes and differences in susceptibility to SARS-CoV-2 is urgent. This review gives an overview of studies employing alternative culture systems like primary cell cultures, tissue explants, or organoids for investigations of the pathophysiology and reverse zoonotic potential of SARS-CoV-2 in animals. In addition, future possibilities of SARS-CoV-2 research in animals, including previously neglected methods like the use of precision-cut lung slices, will be outlined.
      Citation: Veterinary Pathology
      PubDate: 2022-02-08T07:48:21Z
      DOI: 10.1177/03009858211073678
       
  • Comparative pathology of the nasal epithelium in K18-hACE2 Tg mice, hACE2
           Tg mice, and hamsters infected with SARS-CoV-2

    • Free pre-print version: Loading...

      Authors: Pin Yu, Wei Deng, Linlin Bao, Yajin Qu, Yanfeng Xu, Wenjie Zhao, Yunlin Han, Chuan Qin
      Abstract: Veterinary Pathology, Ahead of Print.
      Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes severe viral pneumonia and is associated with a high fatality rate. A substantial proportion of patients infected by SARS-CoV-2 suffer from mild hyposmia to complete loss of olfactory function, resulting in anosmia. However, the pathogenesis of the olfactory dysfunction and comparative pathology of upper respiratory infections with SARS-CoV-2 are unknown. We describe the histopathological, immunohistochemical, and in situ hybridization findings from rodent models of SARS-CoV-2 infection. The main histopathological findings in the olfactory epithelia of K8-hACE2 Tg mice, hACE2 Tg mice, and hamsters were varying degrees of inflammatory lesions, including disordered arrangement, necrosis, exfoliation, and macrophage infiltration of the olfactory epithelia, and inflammatory exudation. On the basis of these observations, the nasal epithelia of these rodent models appeared to develop moderate, mild, and severe rhinitis, respectively. Correspondingly, SARS-CoV-2 viral RNA and antigen were mainly identified in the olfactory epithelia and lamina propria. Moreover, viral RNA was abundant in the cerebrum of K18-hACE2 Tg mice, including the olfactory bulb. The K8-hACE2 Tg mouse, hACE2 Tg mouse, and hamster models could be used to investigate the pathology of SARS-CoV-2 infection in the upper respiratory tract and central nervous system. These models could help to provide a better understanding of the pathogenic process of this virus and to develop effective medications and prophylactic treatments.
      Citation: Veterinary Pathology
      PubDate: 2022-01-29T09:47:58Z
      DOI: 10.1177/03009858211071016
       
  • Investigation of SARS-CoV-2 infection and associated lesions in exotic and
           companion animals

    • Free pre-print version: Loading...

      Authors: David S. Rotstein, Sarah Peloquin, Kathleen Proia, Ellen Hart, Jeongha Lee, Kristin K. Vyhnal, Emi Sasaki, Gayathriy Balamayooran, Javier Asin, Teresa Southard, Laura Rothfeldt, Heather Venkat, Peter Mundschenk, Darby McDermott, Beate Crossley, Pamela Ferro, Gabriel Gomez, Eileen H. Henderson, Paul Narayan, Daniel B. Paulsen, Steven Rekant, Megan E. Schroeder, Rachel M. Tell, Mia Kim Torchetti, Francisco A. Uzal, Ann Carpenter, Ria Ghai
      Abstract: Veterinary Pathology, Ahead of Print.
      Documented natural infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in exotic and companion animals following human exposures are uncommon. Those documented in animals are typically mild and self-limiting, and infected animals have only infrequently died or been euthanized. Through a coordinated One Health initiative, necropsies were conducted on 5 animals from different premises that were exposed to humans with laboratory-confirmed SARS-CoV-2 infection. The combination of epidemiologic evidence of exposure and confirmatory real-time reverse transcriptase-polymerase chain reaction testing confirmed infection in 3 cats and a tiger. A dog was a suspect case based on epidemiologic evidence of exposure but tested negative for SARS-CoV-2. Four animals had respiratory clinical signs that developed 2 to 12 days after exposure. The dog had bronchointerstitial pneumonia and the tiger had bronchopneumonia; both had syncytial-like cells with no detection of SARS-CoV-2. Individual findings in the 3 cats included metastatic mammary carcinoma, congenital renal disease, and myocardial disease. Based on the necropsy findings and a standardized algorithm, SARS-CoV-2 infection was not considered the cause of death in any of the cases. Continued surveillance and necropsy examination of animals with fatal outcomes will further our understanding of natural SARS-CoV-2 infection in animals and the potential role of the virus in development of lesions.
      Citation: Veterinary Pathology
      PubDate: 2022-01-18T09:35:43Z
      DOI: 10.1177/03009858211067467
       
  • Ferrets are valuable models for SARS-CoV-2 research

    • Free pre-print version: Loading...

      Authors: Malgorzata Ciurkiewicz, Federico Armando, Tom Schreiner, Nicole de Buhr, Veronika Pilchová, Vanessa Krupp-Buzimikic, Gülşah Gabriel, Maren von Köckritz-Blickwede, Wolfgang Baumgärtner, Claudia Schulz, Ingo Gerhauser
      Abstract: Veterinary Pathology, Ahead of Print.
      Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulted in an ongoing pandemic with millions of deaths worldwide. Infection of humans can be asymptomatic or result in fever, fatigue, dry cough, dyspnea, and acute respiratory distress syndrome with multiorgan failure in severe cases. The pathogenesis of COVID-19 is not fully understood, and various models employing different species are currently applied. Ferrets can be infected with SARS-CoV-2 and efficiently transmit the virus to contact animals. In contrast to hamsters, ferrets usually show mild disease and viral replication restricted to the upper airways. Most reports have used the intranasal inoculation route, while the intratracheal infection model is not well characterized. Herein, we present clinical, virological, and pathological data from young ferrets intratracheally inoculated with SARS-CoV-2. Infected animals showed no significant clinical signs, and had transient infection with peak viral RNA loads at 4 days postinfection, mild to moderate rhinitis, and pulmonary endothelialitis/vasculitis. Viral antigen was exclusively found in the respiratory epithelium of the nasal cavity, indicating a particular tropism for cells in this location. Viral antigen was associated with epithelial damage and influx of inflammatory cells, including activated neutrophils releasing neutrophil extracellular traps. Scanning electron microscopy of the nasal respiratory mucosa revealed loss of cilia, shedding, and rupture of epithelial cells. The currently established ferret SARS-CoV-2 infection models are comparatively discussed with SARS-CoV-2 pathogenesis in mink, and the advantages and disadvantages of both species as research models for zoonotic betacoronaviruses are highlighted.
      Citation: Veterinary Pathology
      PubDate: 2022-01-08T11:00:45Z
      DOI: 10.1177/03009858211071012
       
  • Immunophenotype of the inflammatory response in the central and enteric
           nervous systems of cockatiels (Nymphicus hollandicus) experimentally
           infected with parrot bornavirus 2

    • Free pre-print version: Loading...

      Authors: Jeann Leal de Araújo, Raquel R. Rech, Aline Rodrigues-Hoffmann, Paula R. Giaretta, Cinthya Cirqueira, Raphael Rocha Wenceslau, Ian Tizard, Josué Diaz-Delgado
      Abstract: Veterinary Pathology, Ahead of Print.
      Proventricular dilatation disease is a lethal disease of psittacine birds. In this study, we characterized the local cellular immune response in the brain, proventriculus, and small intestine of 27 cockatiels (Nymphicus hollandicus) experimentally infected with parrot bornavirus 2 (PaBV-2). Perivascular cuffs in the brain were composed of CD3+ T-lymphocytes and Iba1+ macrophages/microglia in most cockatiels (n = 26). In the ganglia of the proventriculus, CD3+ T-lymphocytes (n = 17) and Iba1+ macrophages (n = 13) prevailed. The ganglia of the small intestine had a more homogeneous distribution of these leukocytes, including PAX5+ B-lymphocytes (n = 9), CD3+ T-lymphocytes (n = 8), and Iba1+ macrophages (n = 8). Our results indicate that perivascular cuffs in the brain and the inflammatory infiltrate in the proventriculus of PaBV-2-infected cockatiels is predominately composed of T-lymphocytes, while the inflammatory infiltrates in the ganglia of the small intestine are characterized by a mixed infiltrate composed of T-lymphocytes, B-lymphocytes, and macrophages.
      Citation: Veterinary Pathology
      PubDate: 2022-01-08T10:56:45Z
      DOI: 10.1177/03009858211069166
       
  • Yokenella regensburgei, a novel pathogen in farmed American alligators

    • Free pre-print version: Loading...

      Authors: Gayathriy Balamayooran, Clark Cooper, Narayan C. Paul, Pamela J. Ferro, Laura Rice, Gabriel Gomez, Josué Díaz-Delgado
      Abstract: Veterinary Pathology, Ahead of Print.
      Increased acute mortality of farmed American alligators (Alligator mississippiensis) was observed in various pens from 2 different farms in Louisiana over 2 years (2019-2021). A total of 14 alligators from multiple events of increased mortality were subjected to postmortem investigations. Except for one alligator with acute neurologic signs, no premonitory signs were observed. All animals had pneumonia (14/14), coelomitis (14/14), and intravascular short Gram-negative bacilli (14/14). Myocarditis (13/14) was common. Yokenella regensburgei was isolated from all alligators tested (13/13). These data suggest the respiratory tract may be a primary target system and could be involved in transmission, either through exhaled bacteria or through swallowing of contaminated respiratory fluids with passage through the feces. Available sensitivity data for Y. regensburgei in this study indicates in vitro sensitivity to aminoglycosides, fluoroquinolones, chloramphenicol, and trimethoprim/sulphamethoxazole antibiotics. Yokenella regensburgei should be included in the differential diagnosis of septicemia and acute death in alligators.
      Citation: Veterinary Pathology
      PubDate: 2022-01-08T10:54:36Z
      DOI: 10.1177/03009858211069165
       
  • Morphological and immunohistochemical characterization and molecular
           classification of spontaneous mammary gland tumors in macropods

    • Free pre-print version: Loading...

      Authors: Tu Chun Hsu, Michael M. Garner, Matti Kiupel
      Abstract: Veterinary Pathology, Ahead of Print.
      Mammary gland neoplasms in macropods are uncommonly reported, and the morphological and immunohistochemical characteristics are incompletely described. The goal of this study was to describe the morphologic features of macropod mammary neoplasms and to determine the molecular subtypes of mammary carcinomas using a panel of antibodies against estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her-2), p63, smooth muscle actin (SMA), and epidermal growth factor receptor (EGFR). Biopsy and necropsy specimens were examined from 21 macropods with mammary tumors submitted to Northwest ZooPath from 1996 to 2019. In accordance with the histologic classification of canine mammary tumors proposed by Goldschmidt and colleagues, tubulopapillary (2), tubular (10), and comedo-carcinomas (2), adenoma (1), lobular hyperplasia (3), fibroadenomatous hyperplasia (1), and mastitis (2) were diagnosed. Red kangaroos (Osphranter rufus) were most commonly diagnosed with mammary carcinomas (79% of all carcinomas). Seven carcinomas had lymphovascular invasion and 2 also had pulmonary metastases. Six of these 7 carcinomas were classified as grade 3. Immunohistochemistry (IHC) for all antibodies was performed on 9/14 carcinomas, and partial IHC was performed for 3 cases. All 12 carcinomas were immunoreactive for PR, 5 for ER, 9 for EGFR, and none for Her-2. Five of the 9 mammary carcinomas with complete IHC data were classified as luminal A subtype, and 4 were normal-like subtype. Accurate classification of mammary tumors in macropods based on morphology, immunohistological characteristics, and molecular subtype may be helpful in guiding clinical management, prognosis, and potential therapeutic targets.
      Citation: Veterinary Pathology
      PubDate: 2022-01-08T10:53:05Z
      DOI: 10.1177/03009858211069164
       
  • Middle East respiratory syndrome coronavirus infection in camelids

    • Free pre-print version: Loading...

      Authors: Nigeer Te, Malgorzata Ciurkiewicz, Judith M. A. van den Brand, Jordi Rodon, Ann-Kathrin Haverkamp, Júlia Vergara-Alert, Albert Bensaid, Bart L. Haagmans, Wolfgang Baumgartner, Joaquim Segalés
      Abstract: Veterinary Pathology, Ahead of Print.
      Middle East respiratory syndrome coronavirus (MERS-CoV) is the cause of a severe respiratory disease with a high case fatality rate in humans. Since its emergence in mid-2012, 2578 laboratory-confirmed cases in 27 countries have been reported by the World Health Organization, leading to 888 known deaths due to the disease and related complications. Dromedary camels are considered the major reservoir host for this virus leading to zoonotic infection in humans. Dromedary camels, llamas, and alpacas are susceptible to MERS-CoV, developing a mild-to-moderate upper respiratory tract infection characterized by epithelial hyperplasia as well as infiltration of neutrophils, lymphocytes, and some macrophages within epithelium, lamina propria, in association with abundant viral antigen. The very mild lesions in the lower respiratory tract of these camelids correlate with absence of overt illness following MERS-CoV infection. Unfortunately, there is no approved antiviral treatment or vaccine for MERS-CoV infection in humans. Thus, there is an urgent need to develop intervention strategies in camelids, such as vaccination, to minimize virus spillover to humans. Therefore, the development of camelid models of MERS-CoV infection is key not only to assess vaccine prototypes but also to understand the biologic mechanisms by which the infection can be naturally controlled in these reservoir species. This review summarizes information on virus-induced pathological changes, pathogenesis, viral epidemiology, and control strategies in camelids, as the intermediate hosts and primary source of MERS-CoV infection in humans.
      Citation: Veterinary Pathology
      PubDate: 2022-01-08T10:47:56Z
      DOI: 10.1177/03009858211069120
       
  • Intervertebral disc degeneration in warmblood horses: Histological and
           biochemical characterization

    • Free pre-print version: Loading...

      Authors: Wilhelmina Bergmann, Chris van de Lest, Saskia Plomp, Johannes C. M. Vernooij, Inge D. Wijnberg, Willem Back, Andrea Gröne, Mark W. Delany, Nermin Caliskan, Marianna A. Tryfonidou, Guy C. M. Grinwis
      First page: 284
      Abstract: Veterinary Pathology, Ahead of Print.
      Gross morphology of healthy and degenerated intervertebral discs (IVDs) is largely similar in horses as in dogs and humans. For further comparison, the biochemical composition and the histological and biochemical changes with age and degeneration were analyzed in 41 warmblood horses. From 33 horses, 139 discs and 2 fetal vertebral columns were evaluated and scored histologically. From 13 horses, 73 IVDs were assessed for hydration, DNA, glycosaminoglycans, total collagen, hydroxyl-lysyl-pyridinoline, hydroxylysine, and advanced glycation end-product (AGE) content. From 7 horses, 20 discs were assessed for aggrecan, fibronectin, and collagen type 1 and 2 content. Histologically, tearing of the nucleus pulposus (NP) and cervical annulus fibrosus (AF), and total histological score (tearing and vascular proliferation of the AF, and chondroid metaplasia, chondrocyte-like cell proliferation, presence of notochordal cells, matrix staining, and tearing of the NP) correlated with gross degeneration. Notochordal cells were not seen in IVDs of horses. Age and gross degeneration were positively correlated with AGEs and a fibrotic phenotype, explaining gross degenerative changes. In contrast to dogs and humans, there was no consistent difference in glycosaminoglycan content and hydration between AF and NP, nor decrease of these variables with age or degeneration. Hydroxylysine decrease and collagen 1 and AGEs increase were most prominent in the NP, suggesting degeneration started in the AP. In caudal cervical NPs, AGE deposition was significantly increased in grossly normal IVDs and total collagen significantly increased with age, suggesting increased biomechanical stress and likelihood for spinal disease in this part of the vertebral column.
      Citation: Veterinary Pathology
      PubDate: 2022-01-04T09:21:46Z
      DOI: 10.1177/03009858211067463
       
  • An inherited night blindness in Wiltshire sheep

    • Free pre-print version: Loading...

      Authors: Hayley Hunt, Keren E. Dittmer, Dorian J. Garrick, Robert A. Fairley, Stephen J. Heap, Robert D. Jolly
      First page: 310
      Abstract: Veterinary Pathology, Ahead of Print.
      Twelve cases of adult-onset blindness were identified in a flock of 130 polled Wiltshire sheep in New Zealand over a 3-year period. Affected sheep developed night blindness between 2 and 3 years of age, which progressed to complete blindness by 4 to 5 years of age. Fundic examination findings included progressive tapetal hyperreflectivity and attenuation of retinal blood vessels. Histologically, the retinas had a selective loss of rod photoreceptors with initial preservation of cone photoreceptors. Retinal degeneration was not accompanied by any other ocular or central nervous system abnormalities, and pedigree analysis suggested an inherited basis for the disease. Mating an affected Wiltshire ram to 2 affected Wiltshire ewes resulted in 6 progeny that all developed retinal degeneration by 2 years of age, while mating of the same affected ram to 6 unaffected ewes resulted in 8 unaffected progeny, consistent with autosomal recessive inheritance. Homozygosity mapping of 5 affected Wiltshire sheep and 1 unaffected Wiltshire sheep using an OvineSNP50 Genotyping BeadChip revealed an identical-by-descent region on chromosome 5, but none of the genes within this region were considered plausible candidate genes. Whole-genome sequencing of 2 affected sheep did not reveal any significant mutations in any of the genes associated with retinitis pigmentosa in humans or progressive retinal atrophy in dogs. Inherited progressive retinal degeneration affecting rod photoreceptors has not been previously reported in sheep, but this disease has several similarities to inherited retinal dystrophies in other species.
      Citation: Veterinary Pathology
      PubDate: 2022-01-03T09:15:27Z
      DOI: 10.1177/03009858211067461
       
  • Medullary bone in male budgerigars (Melopsittacus undulatus) with
           testicular neoplasms

    • Free pre-print version: Loading...

      Authors: Nathan K. Hoggard, Linden E. Craig
      First page: 333
      Abstract: Veterinary Pathology, Ahead of Print.
      Medullary bone is a calcium-rich, labile bone normally occurring in female birds with each egg-laying cycle. The stimulus for formation of medullary bone is, in part, the cyclic increase in serum estrogens produced by preovulatory ovarian follicles. Increased bone density due to formation of medullary bone, particularly in pneumatic bones, has been termed polyostotic hyperostosis, even if physiologic. This study investigated the formation of medullary bone in nonpneumatic (femur) and pneumatic (humerus) bones in sexually mature male budgerigars submitted for autopsy. Of the 21 sexually mature male budgerigars submitted for autopsy, 7 (33%) had medullary bone in 1 or more bones examined. All 7 male budgerigars with medullary bone had a testicular neoplasm, which was morphologically consistent with a testicular sustentacular cell tumor, seminoma, or interstitial cell tumor. Medullary bone was not present in the 14 cases with other diseases. Medullary bone formation in pneumatic and nonpneumatic bones can occur in male budgerigars with testicular neoplasms. Radiographic increases in medullary bone density, particularly in the humerus, could provide antemortem indication of testicular neoplasia in male budgerigars.
      Citation: Veterinary Pathology
      PubDate: 2022-01-08T10:50:05Z
      DOI: 10.1177/03009858211069126
       
  • Trophoblast emboli in the lung of a snowshoe hare (Lepus americanus)

    • Free pre-print version: Loading...

      Authors: Marta Mainenti, Arnaud J. Van Wettere
      First page: 353
      Abstract: Veterinary Pathology, Ahead of Print.
      Spontaneous migration of placental trophoblasts into maternal blood vessels and embolization to other organs (ie, lung, adrenal gland, spleen, and liver) occurs in women and certain animals with hemochorial placentation. Although considered incidental in most species, increased incidence and numbers of trophoblast emboli are reported in women with gestational diseases with arterial hypertension (pre-eclampsia and eclampsia). To the best of our knowledge, trophoblast emboli have not been reported in lagomorphs. This case report describes the identification of trophoblast emboli in the lung of a wild snowshoe hare (Lepus americanus). Death of this hare was attributed to pulmonary hemorrhages and hemothorax, but a definitive cause for the hemorrhages was not determined. It is unclear whether trophoblast embolism normally occurs in this species and represents an incidental finding, or whether it possibly contributed to rupture of pulmonary or thoracic blood vessels leading to hemorrhage.
      Citation: Veterinary Pathology
      PubDate: 2022-01-08T10:58:45Z
      DOI: 10.1177/03009858211071011
       
  • Obituary: Dr Gordon Charles Hard (1931–2021)

    • Free pre-print version: Loading...

      Authors: Carl Alden, Samuel M. Cohen, Wanda M. Haschek-Hock
      First page: 385
      Abstract: Veterinary Pathology, Ahead of Print.

      Citation: Veterinary Pathology
      PubDate: 2022-01-08T11:02:16Z
      DOI: 10.1177/03009858211071013
       
  • Diagnostic challenge in veterinary pathology: Disseminated tumor in a
           young dog

    • Free pre-print version: Loading...

      Authors: Andrea Cappelleri, Luca Bertola, Mario Caniatti, Camilla Recordati
      Abstract: Veterinary Pathology, Ahead of Print.

      Citation: Veterinary Pathology
      PubDate: 2021-12-30T01:47:38Z
      DOI: 10.1177/03009858211067464
       
  • Histologic pulmonary lesions of SARS-CoV-2 in 4 nonhuman primate species:
           An institutional comparative review

    • Free pre-print version: Loading...

      Authors: Chad S. Clancy, Carl Shaia, Vincent Munster, Emmie de Wit, David Hawman, Atsushi Okumura, Heinz Feldmann, Greg Saturday, Dana Scott
      Abstract: Veterinary Pathology, Ahead of Print.
      Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an emergent, amphixenotic infection that resulted in a pandemic declaration in March 2020. A rapid search for appropriate animal models of this newly emergent viral respiratory disease focused initially on traditional nonhuman primate research species. Nonhuman primate models have previously been shown to be valuable in evaluation of emerging respiratory coronaviruses with pandemic potential (ie, SARS-CoV and Middle East respiratory syndrome coronavirus). In this article, we review the pulmonary histopathologic characteristics and immunohistochemical evaluation of experimental SARS-CoV-2 infection in the rhesus macaque, pigtail macaque, African green monkey, and squirrel monkey. Our results indicate that all evaluated nonhuman primate species developed variably severe histopathologic changes typical of coronavirus respiratory disease characterized by interstitial pneumonia with or without syncytial cell formation, alveolar fibrin, and pulmonary edema that progressed to type II pneumocyte hyperplasia. Lesion distribution was multifocal, frequently subpleural, and often more severe in lower lung lobes. However, squirrel monkeys showed the least severe and least consistent lesions of the evaluated nonhuman primates. Additionally, our results highlight the disparate physical relationship between viral antigen and foci of pulmonary lesions. While classic respiratory coronaviral lesions were observed in the lungs of all nonhuman primates evaluated, none of the primates exhibited severe lesions or evidence of diffuse alveolar damage and therefore are unlikely to represent the severe form of SARS-CoV-2 infection observed in fatal human cases.
      Citation: Veterinary Pathology
      PubDate: 2021-12-29T09:14:49Z
      DOI: 10.1177/03009858211067468
       
  • Pulmonary lesions induced by SARS-CoV-2 infection in domestic cats

    • Free pre-print version: Loading...

      Authors: Olivia M. Patania, Shiho Chiba, Peter J. Halfmann, Masato Hatta, Tadashi Maemura, Kristen A. Bernard, Yoshihiro Kawaoka, LaTasha K. Crawford
      Abstract: Veterinary Pathology, Ahead of Print.
      Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019, which ranges from fatal disease in some to mild or subclinical in most affected individuals. Many recovered human patients report persistent respiratory signs; however, lung disease in post-acute infection is poorly understood. Our objective was to describe histologic lung lesions and viral loads following experimental SARS-CoV-2 infection in 11 cats. Microscopic evaluation at 3, 6, 10, or 28 days postinoculation (DPI) identified mild to moderate patchy interstitial pneumonia, bronchiolar epithelial damage, and occlusive histiocytic bronchiolitis. Based on immunohistochemistry, alveolar septal thickening was due to CD204-positive macrophages, fewer B and T lymphocytes, type II pneumocytes, and capillary proliferation with a relative dearth of fibrosis. In blood vessel endothelium, there was reactive hypertrophy or vacuolar degeneration and increased MHC II expression at all time points. Unexpectedly, one cat from the 28 DPI group had severe subacute regionally extensive lymphohistiocytic pneumonia with multifocal consolidation, vasculitis, and alveolar fibrin. Reverse transcriptase-quantitative polymerase chain reaction identified SARS-CoV-2 RNA within the lung at 3 and 6 DPI, and viral RNA was below the limit of detection at 10 and 28 DPI, suggesting that pulmonary lesions persist beyond detection of viral RNA. These findings clarify our comparative understanding of disease induced by SARS-CoV-2 and suggest that cats can serve as an informative model to study post-acute pulmonary sequelae.
      Citation: Veterinary Pathology
      PubDate: 2021-12-29T09:12:10Z
      DOI: 10.1177/03009858211066840
       
  • Chronological brain lesions after SARS-CoV-2 infection in hACE2-transgenic
           mice

    • Free pre-print version: Loading...

      Authors: Enric Vidal, Carlos López-Figueroa, Jordi Rodon, Mónica Pérez, Marco Brustolin, Guillermo Cantero, Víctor Guallar, Nuria Izquierdo-Useros, Jorge Carrillo, Julià Blanco, Bonaventura Clotet, Júlia Vergara-Alert, Joaquim Segalés
      Abstract: Veterinary Pathology, Ahead of Print.
      Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes respiratory disease, but it can also affect other organs including the central nervous system. Several animal models have been developed to address different key questions related to Coronavirus Disease 2019 (COVID-19). Wild-type mice are minimally susceptible to certain SARS-CoV-2 lineages (beta and gamma variants), whereas hACE2-transgenic mice succumb to SARS-CoV-2 and develop a fatal neurological disease. In this article, we aimed to chronologically characterize SARS-CoV-2 neuroinvasion and neuropathology. Necropsies were performed at different time points, and the brain and olfactory mucosa were processed for histopathological analysis. SARS-CoV-2 virological assays including immunohistochemistry were performed along with a panel of antibodies to assess neuroinflammation. At 6 to 7 days post inoculation (dpi), brain lesions were characterized by nonsuppurative meningoencephalitis and diffuse astrogliosis and microgliosis. Vasculitis and thrombosis were also present and associated with occasional microhemorrhages and spongiosis. Moreover, there was vacuolar degeneration of virus-infected neurons. At 2 dpi, SARS-CoV-2 immunolabeling was only found in the olfactory mucosa, but at 4 dpi intraneuronal virus immunolabeling had already reached most of the brain areas. Maximal distribution of the virus was observed throughout the brain at 6 to 7 dpi except for the cerebellum, which was mostly spared. Our results suggest an early entry of the virus through the olfactory mucosa and a rapid interneuronal spread of the virus leading to acute encephalitis and neuronal damage in this mouse model.
      Citation: Veterinary Pathology
      PubDate: 2021-12-27T09:19:12Z
      DOI: 10.1177/03009858211066841
       
  • Hamster models of COVID-19 pneumonia reviewed: How human can they be'

    • Free pre-print version: Loading...

      Authors: Achim D. Gruber, Theresa C. Firsching, Jakob Trimpert, Kristina Dietert
      Abstract: Veterinary Pathology, Ahead of Print.
      The dramatic global consequences of the coronavirus disease 2019 (COVID-19) pandemic soon fueled quests for a suitable model that would facilitate the development and testing of therapies and vaccines. In contrast to other rodents, hamsters are naturally susceptible to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the Syrian hamster (Mesocricetus auratus) rapidly developed into a popular model. It recapitulates many characteristic features as seen in patients with a moderate, self-limiting course of the disease such as specific patterns of respiratory tract inflammation, vascular endothelialitis, and age dependence. Among 4 other hamster species examined, the Roborovski dwarf hamster (Phodopus roborovskii) more closely mimics the disease in highly susceptible patients with frequent lethal outcome, including devastating diffuse alveolar damage and coagulopathy. Thus, different hamster species are available to mimic different courses of the wide spectrum of COVID-19 manifestations in humans. On the other hand, fewer diagnostic tools and information on immune functions and molecular pathways are available than in mice, which limits mechanistic studies and inference to humans in several aspects. Still, under pandemic conditions with high pressure on progress in both basic and clinically oriented research, the Syrian hamster has turned into the leading non-transgenic model at an unprecedented pace, currently used in innumerable studies that all aim to combat the impact of the virus with its new variants of concern. As in other models, its strength rests upon a solid understanding of its similarities to and differences from the human disease, which we review here.
      Citation: Veterinary Pathology
      PubDate: 2021-12-03T07:20:27Z
      DOI: 10.1177/03009858211057197
       
  • Influence of SARS-CoV-2 on airway mucus production: A review and proposed
           model

    • Free pre-print version: Loading...

      Authors: David K. Meyerholz, Leah R. Reznikov
      Abstract: Veterinary Pathology, Ahead of Print.
      Coronavirus disease 2019 (COVID-19) is a worldwide pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has affected millions of lives. Individuals who survive severe COVID-19 can experience sustained respiratory symptoms that persist for months after initial infection. In other airway diseases, abnormal airway mucus contributes to sustained airway symptoms. However, the impact of SARS-CoV-2 on airway mucus has received limited attention. In the current review, we assess literature describing the impact of SARS-CoV-2 on airway pathophysiology with specific emphasis on mucus production. Accumulating evidence suggests that the 2 major secreted airway mucin glycoproteins, MUC5AC and MUC5B, are abnormal in some patients with COVID-19. Aberrations in MUC5AC or MUC5B in response to SARS-CoV-2 infection are likely due to inflammation, though the responsible mechanisms have yet to be determined. Thus, we also provide a proposed model highlighting mechanisms that can contribute to acute and sustained mucus abnormalities in SARS-CoV-2, with an emphasis on inflammatory cells and mediators, including mast cells and histamine. Last, we bring to light the challenges of studying abnormal mucus production in SARS-CoV-2 infections and discuss the strengths and limitations of model systems commonly used to study COVID-19. The evidence to date suggests that ferrets, nonhuman primates, and cats may have advantages over other models to investigate mucus in COVID-19.
      Citation: Veterinary Pathology
      PubDate: 2021-11-19T03:20:34Z
      DOI: 10.1177/03009858211058837
       
  • Cellular tropism of SARS-CoV-2 in the respiratory tract of Syrian hamsters
           and B6.Cg-Tg(K18-ACE2)2Prlmn/J transgenic mice

    • Free pre-print version: Loading...

      Authors: Hui-Ling Yen, Sophie Valkenburg, Sin Fun Sia, Ka Tim Choy, J. S. Malik Peiris, Karen H. M. Wong, Nicholas Crossland, Florian Douam, John M. Nicholls
      Abstract: Veterinary Pathology, Ahead of Print.
      Several animal models have been developed to study the pathophysiology of SARS-CoV-2 infection and to evaluate vaccines and therapeutic agents for this emerging disease. Similar to infection with SARS-CoV-1, infection of Syrian hamsters with SARS-CoV-2 results in moderate respiratory disease involving the airways and lung parenchyma but does not lead to increased mortality. Using a combination of immunohistochemistry and transmission electron microscopy, we showed that the epithelium of the conducting airways of hamsters was the primary target for viral infection within the first 5 days of infection, with little evidence of productive infection of pneumocytes. At 6 days postinfection, antigen was cleared but parenchymal damage persisted, and the major pathological changes resolved by day 14. These findings are similar to those previously reported for hamsters with SARS-CoV-1 infection. In contrast, infection of K18-hACE2 transgenic mice resulted in pneumocyte damage, with viral particles and replication complexes in both type I and type II pneumocytes together with the presence of convoluted or cubic membranes; however, there was no evidence of virus replication in the conducting airways. The Syrian hamster is a useful model for the study of SARS-CoV-2 transmission and vaccination strategies, whereas infection of the K18-hCE2 transgenic mouse results in lethal disease with fatal neuroinvasion but with sparing of conducting airways.
      Citation: Veterinary Pathology
      PubDate: 2021-09-01T09:09:19Z
      DOI: 10.1177/03009858211043084
       
  • Diagnostic Challenge in Veterinary Pathology: Alopecic Crusting Dermatitis
           in a Goat

    • Free pre-print version: Loading...

      Authors: Jason D. Struthers, Clemence Chako, Stephani Ruppert, Kenneth Jackson, Patricia A. Pesavento
      First page: 182
      Abstract: Veterinary Pathology, Ahead of Print.

      Citation: Veterinary Pathology
      PubDate: 2021-12-07T03:40:29Z
      DOI: 10.1177/03009858211062635
       
  • Listeria monocytogenes at the interface between ruminants and humans: A
           comparative pathology and pathogenesis review

    • Free pre-print version: Loading...

      Authors: Stefano Bagatella, Leticia Tavares-Gomes, Anna Oevermann
      First page: 186
      Abstract: Veterinary Pathology, Ahead of Print.
      The bacterium Listeria monocytogenes (Lm) is widely distributed in the environment as a saprophyte, but may turn into a lethal intracellular pathogen upon ingestion. Invasive infections occur in numerous species worldwide, but most commonly in humans and farmed ruminants, and manifest as distinct forms. Of those, neuroinfection is remarkably threatening due to its high mortality. Lm is widely studied not only as a pathogen but also as an essential model for intracellular infections and host-pathogen interactions. Many aspects of its ecology and pathogenesis, however, remain unclear and are rarely addressed in its natural hosts. This review highlights the heterogeneity and adaptability of Lm by summarizing its association with the environment, farm animals, and disease. It also provides current knowledge on key features of the pathology and (molecular) pathogenesis of various listeriosis forms in naturally susceptible species with a special focus on ruminants and on the neuroinvasive form of the disease. Moreover, knowledge gaps on pathomechanisms of listerial infections and relevant unexplored topics in Lm pathogenesis research are highlighted.
      Citation: Veterinary Pathology
      PubDate: 2021-12-03T07:22:05Z
      DOI: 10.1177/03009858211052659
       
  • Computer-assisted mitotic count using a deep learning–based algorithm
           improves interobserver reproducibility and accuracy

    • Free pre-print version: Loading...

      Authors: Christof A. Bertram, Marc Aubreville, Taryn A. Donovan, Alexander Bartel, Frauke Wilm, Christian Marzahl, Charles-Antoine Assenmacher, Kathrin Becker, Mark Bennett, Sarah Corner, Brieuc Cossic, Daniela Denk, Martina Dettwiler, Beatriz Garcia Gonzalez, Corinne Gurtner, Ann-Kathrin Haverkamp, Annabelle Heier, Annika Lehmbecker, Sophie Merz, Erica L. Noland, Stephanie Plog, Anja Schmidt, Franziska Sebastian, Dodd G. Sledge, Rebecca C. Smedley, Marco Tecilla, Tuddow Thaiwong, Andrea Fuchs-Baumgartinger, Donald J. Meuten, Katharina Breininger, Matti Kiupel, Andreas Maier, Robert Klopfleisch
      First page: 211
      Abstract: Veterinary Pathology, Ahead of Print.
      The mitotic count (MC) is an important histological parameter for prognostication of malignant neoplasms. However, it has inter- and intraobserver discrepancies due to difficulties in selecting the region of interest (MC-ROI) and in identifying or classifying mitotic figures (MFs). Recent progress in the field of artificial intelligence has allowed the development of high-performance algorithms that may improve standardization of the MC. As algorithmic predictions are not flawless, computer-assisted review by pathologists may ensure reliability. In the present study, we compared partial (MC-ROI preselection) and full (additional visualization of MF candidates and display of algorithmic confidence values) computer-assisted MC analysis to the routine (unaided) MC analysis by 23 pathologists for whole-slide images of 50 canine cutaneous mast cell tumors (ccMCTs). Algorithmic predictions aimed to assist pathologists in detecting mitotic hotspot locations, reducing omission of MFs, and improving classification against imposters. The interobserver consistency for the MC significantly increased with computer assistance (interobserver correlation coefficient, ICC = 0.92) compared to the unaided approach (ICC = 0.70). Classification into prognostic stratifications had a higher accuracy with computer assistance. The algorithmically preselected hotspot MC-ROIs had a consistently higher MCs than the manually selected MC-ROIs. Compared to a ground truth (developed with immunohistochemistry for phosphohistone H3), pathologist performance in detecting individual MF was augmented when using computer assistance (F1-score of 0.68 increased to 0.79) with a reduction in false negatives by 38%. The results of this study demonstrate that computer assistance may lead to more reproducible and accurate MCs in ccMCTs.
      Citation: Veterinary Pathology
      PubDate: 2021-12-30T09:33:15Z
      DOI: 10.1177/03009858211067478
       
  • Immunophenotyping of intraepithelial lymphocytes in canine chronic
           enteropathy and intestinal T-cell lymphoma using endoscopic samples

    • Free pre-print version: Loading...

      Authors: Kazuhiro Kojima, James K. Chambers, Ko Nakashima, Yuko Goto-Koshino, Kazuyuki Uchida
      First page: 227
      Abstract: Veterinary Pathology, Ahead of Print.
      Human enteropathy-associated T-cell lymphoma (EATL) is considered to be derived from intraepithelial lymphocytes (IELs); however, the origin of canine intestinal T-cell lymphoma (ITCL) remains unclear. Histological, immunohistochemical, and clonality examinations were performed using endoscopically collected canine duodenum samples of mucosal lesions of chronic enteropathy (CE; 73 cases) and ITCL without transmural neoplastic mass lesions (64 cases). Histopathological examinations revealed the intraepithelial accumulation of lymphocytes (called “intraepithelial lymphocytosis”) in 54/73 CE cases (74%) and the epitheliotropism of neoplastic lymphocytes in 63/64 ITCL cases (98%). Immunohistochemically, IELs in CE with intraepithelial lymphocytosis (IEL+CE) were diffusely immunopositive for CD3, with scattered immunopositivity for CD5, CD8, CD20, and granzyme B (GRB). The percentage of CD8+ in CD3+ IELs was significantly lower in IEL+CE than in CE without intraepithelial lymphocytosis (IEL−CE). Double-labeling immunohistochemistry revealed a high percentage of GRB expression in CD8− IEL among IEL+CE. Among 64 ITCL cases, CD3 was immunopositive in 64 (100%), CD5 in 22 (34%), CD8 in 8 (13%), CD20 in 12 (19%), CD30 in 13 (20%), and GRB in 49 (77%). In CD3+ cells, Ki67 immunopositivity was highest in ITCL, intermediate in IEL+CE, and lower in IEL−CE. A clonal TCR gene rearrangement was detected in 1/19 IEL−CE cases (5%), 15/54 IEL+CE (28%), and 38/58 ITCL (66%). These results indicate that the immunophenotype of canine ITCL (CD8−GRB+) is similar to that of the increased IELs in CE. The high proliferative activity and clonality of T cells in IEL+CE suggest that canine ITCL originates from these IELs, similar to human EATL.
      Citation: Veterinary Pathology
      PubDate: 2021-11-19T03:23:36Z
      DOI: 10.1177/03009858211057220
       
  • Carboxypeptidase A3 expression in canine mast cell tumors and
           tissue-resident mast cells

    • Free pre-print version: Loading...

      Authors: Sanna Hämäläinen, Lauri Kareinen, Antti Sukura, Ilona Kareinen
      First page: 236
      Abstract: Veterinary Pathology, Ahead of Print.
      Mast cell tumors (MCTs) are one of the most common cutaneous malignancies in dogs. Previous studies have reported expression of mast cell–specific proteases chymase and tryptase in canine cutaneous MCTs and in connective tissue and mucosal mast cells. In humans and rodents, mast cells express an additional specific protease, carboxypeptidase A3 (CPA3). In this article, we describe CPA3 immunoreactivity in connective tissue, visceral, mucosal, and neoplastic mast cells in dogs. Positive immunolabeling for CPA3 was observed in nonneoplastic mast cells in 20/20 formalin-fixed paraffin-embedded normal tissues (skin, liver, spleen, intestine), and in 63/63 MCTs irrespective of their histological grade. CPA3 protein expression was comparable to that of c-kit in both the nonneoplastic and neoplastic mast cells. Three distinct labeling patterns (membranous, diffuse, and focal cytoplasmic) were observed for CPA3 in MCTs. The focal cytoplasmic labeling pattern was associated with high-grade MCTs staged with the Kiupel 2-tier grading criteria. We propose CPA3 as a novel immunohistochemical marker for canine mast cells in health and disease.
      Citation: Veterinary Pathology
      PubDate: 2021-12-13T02:40:54Z
      DOI: 10.1177/03009858211062636
       
  • Canine smooth muscle tumors: A clinicopathological study

    • Free pre-print version: Loading...

      Authors: Giancarlo Avallone, Valeria Pellegrino, Luisa Vera Muscatello, Paola Roccabianca, Gastone Castellani, Claudia Sala, Marco Tecilla, Paola Valenti, Giuseppe Sarli
      First page: 244
      Abstract: Veterinary Pathology, Ahead of Print.
      Canine smooth muscle tumors (SMTs) commonly develop in the alimentary and female genital tracts and less frequently in soft tissue. The definition of histological criteria of malignancy is less detailed for SMTs in dogs than in humans. This study evaluated the clinicopathologic features of canine SMTs and compared the veterinary and human medical criteria of malignancy. A total of 105 canine SMTs were evaluated histologically and classified according to both veterinary and human criteria. The Ki67 labeling index was assessed in all SMTs. Estrogen receptor (ER) and progesterone receptor (PR) expression was evaluated for soft tissue SMTs. Follow-up data were available in 25 cases. SMTs were diagnosed in the female genital tract (42%), alimentary tract (22%), and soft tissue (20%). Soft tissue SMTs frequently arose in the perigenital area, pelvic cavity, and retroperitoneum. A subset of soft tissue SMTs expressed ER and/or PR, resembling the gynecologic type of soft tissue SMT in humans. SMTs were less frequently malignant when assessed with human criteria than with veterinary criteria, better reflecting their benign behavior, especially in the genital tract where human criteria tolerate a higher mitotic count for leiomyoma. Decreased differentiation was correlated with increased proliferation, necrosis, and reduced desmin expression. Mitotic count, Ki67 labeling index, and necrosis were correlated with metastases and tumor-related death. Further prognostic studies are warranted to confirm the better performance of the human criteria when assessing SMT malignancy, especially genital cases, to confirm their usefulness in ER/PR-expressing soft tissue SMTs, and to better define the most useful prognostic parameters for canine SMTs.
      Citation: Veterinary Pathology
      PubDate: 2021-12-27T09:20:18Z
      DOI: 10.1177/03009858211066862
       
  • Teat sinus and duct adenomatous hyperplasia in dogs

    • Free pre-print version: Loading...

      Authors: F. Yvonne Schulman, Michael H. Goldschmidt, Michael Hardcastle, Valentina E. G. Zappulli
      First page: 256
      Abstract: Veterinary Pathology, Ahead of Print.
      Seventeen lesions diagnosed as teat sinus and duct adenomatous hyperplasia were identified in 10 dogs. All of the dogs were small breeds. Six were spayed female and 4 were male, 3 castrated and 1 intact. In 5 cases, the lesions involved multiple teats. They were pink to black, flattened to round, and sometimes crusted. Histologically, the lesions were usually pigmented (16/17), plaque-like to nodular masses composed of polygonal cells arranged in anastomosing trabeculae and bilayered ducts and/or cysts, with a fibrous to mucinous (Alcian blue-positive) stroma and squamous cysts (12/17). Scattered epithelial cells contained single, discrete, clear cytoplasmic vacuoles. Atypia was mild, and the mitotic count per 2.37 mm2 varied from 0 to 15 (average 2.7). Immunohistochemistry was performed on 14 of the lesions from 8 dogs. Epithelial cells were 100% panCK+ and included basally located CK14+/CK5_6+/p63+/calponin− cells and nonbasal CK19+/CK7+ cells. Cells manifesting squamous differentiation were usually panCK+/CK14+/CK5_6+/CK19−/CK7−/p63±/calponin−. In addition to fibroblasts, vimentin positivity was found in disseminated, round to stellate stromal and intraepithelial cells that often had black, granular, cytoplasmic pigment (consistent with dendritic/phagocytic cells and/or melanocytes). Of the 8 dogs for which clinical follow-up information was available, all were still alive and well, with no significant teat changes, development of mammary lesions or other masses 4 to 22 months (median 12.5) after biopsy. The histologic, immunohistochemical, and clinical findings were consistent with teat duct and sinus adenomatous hyperplasia. This is an uncommon, benign proliferative lesion that can involve multiple teats of female and male, small breed dogs.
      Citation: Veterinary Pathology
      PubDate: 2021-11-19T03:25:16Z
      DOI: 10.1177/03009858211058829
       
  • Periarticular plasma cell tumors in cats

    • Free pre-print version: Loading...

      Authors: Linden E. Craig, Danielle E. Lieske
      First page: 264
      Abstract: Veterinary Pathology, Ahead of Print.
      This report describes periarticular plasma cell tumors with abundant amyloid in 11 cats. The tarsus was the most commonly affected joint (10/11), and the masses were often circumferential around the tarsal joint, involving the dermis and subcutis. The 2 cases in which synovium was examined had neoplastic cells expanding the synovium. Three of the 5 cases staged radiographically had bony lysis of the affected joint. Cutaneous biopsy specimens often consisted of more amyloid than plasma cells, making the diagnosis difficult on small samples. Follow-up information was available in 7 cases; in those cases, the median survival was 194 days (range 53–671 days). Four cases had confirmed metastases, most often to regional lymph nodes, liver, and spleen. Although canine cutaneous plasma cell tumors are typically benign, those with abundant amyloid surrounding the joints of cats may involve deeper tissues and have a more aggressive behavior. These tumors can be difficult to diagnose due to low cellularity and abundant amyloid.
      Citation: Veterinary Pathology
      PubDate: 2021-11-12T03:14:32Z
      DOI: 10.1177/03009858211048621
       
  • Feline hypertrophic cardiomyopathy: reduced microvascular density and
           involvement of CD34+ interstitial cells

    • Free pre-print version: Loading...

      Authors: Josep M. Monné Rodríguez, Sonja Fonfara, Udo Hetzel, Anja Kipar
      First page: 269
      Abstract: Veterinary Pathology, Ahead of Print.
      The sequence of pathological events in feline hypertrophic cardiomyopathy (fHCM) is still largely unknown, although we know that fHCM is characterized by interstitial remodeling in a macrophage-driven pro-inflammatory environment and that myocardial ischemia might contribute to its progression. This study aimed to gain further insights into the structural changes associated with interstitial remodeling in fHCM with special focus on the myocardial microvasculature and the phenotype of the interstitial cells. Twenty-eight hearts (16 hearts with fHCM and 12 without cardiac disease) were evaluated in the current study, with immunohistochemistry, RNA-in situ hybridization, and transmission electron microscopy. Morphometrical evaluations revealed a statistically significant lower microvascular density in fHCM. This was associated with structural alterations in capillaries that go along with a widening of the interstitium due to the accumulation of edema fluid, collagen fibers, and mononuclear cells that also proliferated locally. The interstitial cells were mainly of fibroblastic or vascular phenotype, with a substantial contribution of predominantly resident macrophages. A large proportion expressed CD34 mRNA, which suggests a progenitor cell potential. Our results indicate that microvascular alterations are key events in the pathogenesis of fHCM and that myocardial interstitial cell populations with CD34+ phenotype play a role in the pathogenesis of the disease.
      Citation: Veterinary Pathology
      PubDate: 2021-12-27T09:17:39Z
      DOI: 10.1177/03009858211062631
       
  • Fox (Vulpes vulpes) involvement identified in a series of cat carcass
           mutilations

    • Free pre-print version: Loading...

      Authors: Kita D. Hull, Sonja Jeckel, Jonathan M. Williams, Sherryn A. Ciavaglia, Lucy M. I. Webster, Ella Fitzgerald, Yu-Mei Chang, Henny M. Martineau
      First page: 299
      Abstract: Veterinary Pathology, Ahead of Print.
      This study was designed to identify the cause of mutilation and death in 32 cats, part of a larger cohort found dead in Greater London, the United Kingdom, between 2016 and 2018. At the time, discussion in the media led to concerns of a human serial cat killer (dubbed The Croydon Cat Killer) pursuing domestic cats, causing a state of disquietude. Given the link between animal abuse and domestic violence, human intervention had to be ruled out. Using a combination of DNA testing, computed tomography imaging, and postmortem examination, no evidence was found to support any human involvement. Instead, a significant association between cat carcass mutilation and the presence of fox DNA was demonstrated. Gross examination identified shared characteristics including the pattern of mutilation, level of limb or vertebral disarticulation, wet fur, wound edges with shortened fur, and smooth or irregular contours, and marks in the skin, muscle, and bone consistent with damage from carnivore teeth. Together these findings supported the theory that the cause of mutilation was postmortem scavenging by red foxes (Vulpes vulpes). The probable cause of death was established in 26/32 (81%) carcasses: 10 were predated, 8 died from cardiorespiratory failure, 6 from blunt force trauma, one from ethylene glycol toxicity, and another from liver failure. In 6 carcasses a cause of death was not established due to autolysis and/or extensive mutilation. In summary, this study highlights the value of a multidisciplinary approach to fully investigate cases of suspected human-inflicted mutilation of animals.
      Citation: Veterinary Pathology
      PubDate: 2021-12-07T03:33:31Z
      DOI: 10.1177/03009858211052661
       
  • Macrophages in dermal disease progression of phospholipase
           D4–deficient Fleckvieh calves

    • Free pre-print version: Loading...

      Authors: Martin C. Langenmayer, Simone Jung, Robert Fux, Christina Wittlinger, Theresa Tschoner, Monir Majzoub-Altweck, Gabriela Knubben-Schweizer, Ruedi Fries, Walter Hermanns, Florian M. Trefz
      First page: 319
      Abstract: Veterinary Pathology, Ahead of Print.
      A new gene defect in Fleckvieh calves leads to a syndrome with partial phenotype overlap with bovine hereditary zinc deficiency. A mutation in a gene encoding phospholipase D4 (PLD4), an endosomal exonuclease, causes the disorder. In mice, PLD4 activity indirectly regulates the Toll-like receptor 9 (TLR9) pathway via degradation of microbial DNA. PLD4 absence thus results in visceral macrophage activation comparable to human macrophage activation syndrome. In this study, disease progression and the role of macrophages in affected calves were monitored clinically, clinicopathologically, and histologically over time. Breeding data identified 73 risk matings of heterozygous carriers resulting in 54 potentially PLD4-deficient calves born on farms. PLD4 status was examined via 5′-exonuclease assay, detecting 6 calves carrying the defect. These were purchased and monitored daily until final necropsy. The calves developed progressive skin lesions starting with small scaling areas terminating in severe crusting dermatitis, especially in areas with mechanical exposure. Histological and immunohistochemical analyses indicated that macrophages with cytoplasmic vacuolation increased considerably in skin sections obtained weekly during the disease course. Macrophage increase correlated with increased dermal lesion severity. Macrophage activation was confirmed by prominent phagocytic activity in the superficial dermis using electron microscopy. Dermal mRNA abundance of CCL2 and CCL3 measured by quantitative polymerase chain reaction verified macrophage activation. Further increase in mRNA of downstream molecule MyD88 and cytokine IL12b connected bovine PLD4 deficiency to increased TLR9 pathway activation. In contrast to human macrophage activation syndrome, the main feature of bovine PLD4 deficiency was local disease in organs with contact to microbial DNA (skin, intestine, lungs).
      Citation: Veterinary Pathology
      PubDate: 2021-12-03T07:23:45Z
      DOI: 10.1177/03009858211062629
       
  • Heterogeneous immunoreactivity of axonal spheroids in focal symmetrical
           encephalomalacia produced by Clostridium perfringens type D epsilon toxin
           in sheep

    • Free pre-print version: Loading...

      Authors: Jim Manavis, Peter Blumbergs, Ian Jerrett, Daren Hanshaw, Francisco Uzal, John Finnie
      First page: 328
      Abstract: Veterinary Pathology, Ahead of Print.
      Since axonal injury (AI) is an important component of many veterinary neurologic disorders, we assessed the relative ability of a panel of antibodies (amyloid precursor protein, 3 subunits of neurofilament protein, protein gene product 9.5, ubiquitin, and synaptophysin) to detect axonal swellings or spheroids. Abundant axonal spheroids found in necrotic internal capsule foci produced in 4 sheep by chronic Clostridium perfringens type D epsilon neurotoxicity provided a model system in which to evaluate this important diagnostic tool. There was heterogeneous labeling of subsets of spheroids by the respective antibodies, suggesting that, in order to detect the complete spectrum of AI in diagnostic cases, a range of antibodies should be used, not only when spheroids are plentiful but also when they are few in number or incompletely developed. The application of insufficient markers in the latter cases can potentially lead to the contribution of AI to lesion pathogenesis being underappreciated.
      Citation: Veterinary Pathology
      PubDate: 2021-12-07T03:39:09Z
      DOI: 10.1177/03009858211057222
       
  • AA-amyloidosis in captive northern tree shrews (Tupaia belangeri)

    • Free pre-print version: Loading...

      Authors: Annette Klein, Ute Radespiel, Felix Felmy, Tina Brezina, Malgorzata Ciurkiewicz, Jessica Schmitz, Jan Hinrich Bräsen, Reinhold Paul Linke, Sina Reinartz, Ottmar Distl, Andreas Beineke
      First page: 340
      Abstract: Veterinary Pathology, Ahead of Print.
      A high prevalence of AA-amyloidosis was identified in a breeding colony of northern tree shrews (Tupaia belangeri) in a retrospective analysis, with amyloid deposits in different organs being found in 26/36 individuals (72%). Amyloid deposits, confirmed by Congo red staining, were detected in kidneys, intestines, skin, and lymph nodes, characteristic of systemic amyloidosis. Immunohistochemically, the deposited amyloid was intensely positive with anti-AA-antibody (clone mc4), suggesting AA-amyloidosis. The kidneys were predominantly affected (80%), where amyloid deposits ranged from mild to severe and was predominantly located in the renal medulla. In addition, many kidneys contained numerous cysts with atrophy of the renal parenchyma. There was no significant association between concurrent neoplastic or inflammatory processes and amyloidosis. The lack of distinctive predisposing factors suggests a general susceptibility of captive T. belangeri to develop amyloidosis. Clinical and laboratory findings of a female individual with pronounced kidney alterations were indicative of renal failure. The observed tissue tropism with pronounced kidney alterations, corresponding renal dysfunction, and an overall high prevalence suggests amyloidosis as an important disease in captive tree shrews.
      Citation: Veterinary Pathology
      PubDate: 2021-12-21T10:55:35Z
      DOI: 10.1177/03009858211066847
       
  • A novel herpes-like virus inducing branchial lesions in a tiger shark
           (Galeocerdo cuvier)

    • Free pre-print version: Loading...

      Authors: Abigail R. Armwood, Justin M. Stilwell, Terry Fei Fan Ng, Tonya M. Clauss, John H. Leary, Doug Mader, Alvin C. Camus
      First page: 348
      Abstract: Veterinary Pathology, Ahead of Print.
      A juvenile, male tiger shark (Galeocerdo cuvier) developed illness after capture in Florida waters and was euthanized. Gross lesions included mild skin abrasions, hepatic atrophy, and coelomic fluid. Histologically, gills contained multifocal lamellar epithelial cell necrosis and thromboses. Scattered gill and esophageal epithelial cells had large, basophilic, intracytoplasmic, and intranuclear inclusions. Ultrastructurally, lamellar epithelial cells contained arrays of intracytoplasmic viral particles and scattered intranuclear nucleocapsids. Capsulated virions were 148 ± 11 nm with an 84 ± 8 nm icosahedral nucleocapsid and an electron-dense core. Next-generation sequencing, quantitative polymerase chain reaction, and in situ hybridization performed on formalin-fixed tissue confirmed a herpes-like viral infection. The viral polymerase shared 24% to 31% protein homology with other alloherpesviruses of fish, indicating a divergent virus. This report documents the pathologic findings associated with a molecularly confirmed novel herpes-like virus in an elasmobranch.
      Citation: Veterinary Pathology
      PubDate: 2021-11-19T03:21:56Z
      DOI: 10.1177/03009858211052662
       
  • Vascular, cardiac, and renal lesions attributed to primary systemic
           hypertension in western pygmy marmosets (Cebuella pygmaea)

    • Free pre-print version: Loading...

      Authors: Avery James Cooley, Anne Savage, Charles T. Snowdon
      First page: 358
      Abstract: Veterinary Pathology, Ahead of Print.
      In a retrospective study of a western pygmy marmoset (Cebuella pygmaea) colony, postmortem examination of 1/8 juvenile and 29/47 adult animals identified vascular, cardiac, and renal lesions consistent with systemic hypertension. This included frequent renal arteriolar hypertrophy, hyaline and proliferative arteriolosclerosis, fibrinoid necrosis of arterioles, glomerulosclerosis, and nephrosclerosis. Affected animals ranged from 0.6 to 12 years of age (mean 6 years) and had an observed male predominance. Genealogical relatedness was evident in several breeding pairs and spanned multiple generations. Concurrent cardiac and renal disease was commonly identified, although frequently subclinical, and both were important causes of morbidity and mortality in affected animals. Cardiomegaly and hypertrophy were typical features and were accompanied by left atrial thrombosis in 10 animals. Signs of heart failure included chronic pulmonary edema in 20 cases and body cavity effusions in 17. In the kidneys, 19 cases had glomerular disease and hypertensive vasculopathy, and 26 cases had nephrosclerosis or glomerulosclerosis. Common extrarenal secondary causes of hypertension were excluded by necropsy examination. The pathogenesis is suggested to involve primary hypertension leading to renal and cardiac disease. Elevated sympathetic activity might be an underlying factor in the frequent development of primary systemic hypertension in the pygmy marmoset, as for the owl monkey.
      Citation: Veterinary Pathology
      PubDate: 2021-12-07T03:36:09Z
      DOI: 10.1177/03009858211052664
       
  • Morphology and cyclooxygenase-2 and renin expression in the kidney of
           young spontaneously hypertensive rats

    • Free pre-print version: Loading...

      Authors: Carmen G. Mondragón-Huerta, Rocío Bautista-Pérez, Luis A. Baiza-Gutman, María L. Escobar-Sánchez, Leonardo Del Valle-Mondragón, Carlos Gerardo Salas-Garrido, Patricia Castro-Moreno, Maximiliano Ibarra-Barajas
      First page: 371
      Abstract: Veterinary Pathology, Ahead of Print.
      The kidneys play an important role in blood pressure regulation under normal and pathological conditions. We examined the histological changes and expression patterns of cyclooxygenase-2, renin, and (pro)renin receptor (PRR) in the renal cortex of prehypertensive spontaneously hypertensive rats (SHRs) and Wistar Kyoto rats (WKYs). Moreover, blood pressure and plasma urea, creatinine, angiotensin II, and angiotensin (1–7) levels were measured. The results showed that both strains had similar blood pressure and plasma urea and creatinine levels. The glomerular area, basement membrane thickness, collagen fiber content, and arterial wall thickness were greater in SHRs than in WKYs. By immunohistochemistry, cyclooxygenase-2 was localized in the macula densa and renal tubules of both strains. In SHRs, cyclooxygenase-2 was detected in a larger number of tubules, and the cortical expression of cyclooxygenase-2 was also increased. In both strains, PRR and renin were localized in the tubular epithelium and juxtaglomerular cells, respectively. In SHRs, PRR immunolocalization was increased in the glomerulus. The cortical expression of immature renin was markedly increased in SHRs compared to that in WKYs, while renin was significantly decreased. These changes were associated with higher plasma angiotensin II levels and lower plasma angiotensin (1–7) levels in SHRs. The results indicate that the kidneys of SHRs showed morphological changes and variations in cortical expression patterns of PRR, cyclooxygenase-2, and renin before the development of hypertension.
      Citation: Veterinary Pathology
      PubDate: 2021-11-29T02:09:18Z
      DOI: 10.1177/03009858211052663
       
 
JournalTOCs
School of Mathematical and Computer Sciences
Heriot-Watt University
Edinburgh, EH14 4AS, UK
Email: journaltocs@hw.ac.uk
Tel: +00 44 (0)131 4513762
 


Your IP address: 100.24.115.215
 
Home (Search)
API
About JournalTOCs
News (blog, publications)
JournalTOCs on Twitter   JournalTOCs on Facebook

JournalTOCs © 2009-