Veterinary Pathology最新文献

Amyloid precursor protein (APP) is the most sensitive early immunomarker of axonal injury in the brain. Currently, there are several commercially available antibodies to detect axonal spheroids expressing APP. However, immunolabeling of a given molecule can be variable when antibodies are directed to different epitopes. In this study, we optimized a panel of antibodies (22C11, Y188, NAB228, C1/6.1) for labeling APP-immunopositive axonal spheroids in ovine brains and compared the patterns of injury in brains containing spheroids from neurotoxic (clostridial focal symmetrical encephalomalacia [FSE]) and traumatic brain injury. The pattern of axonal spheroid immunolabeling in FSE necrotic foci and trauma-damaged white matter was similar with all 4 antibodies. Only subtle differences in axonal immunolabeling were found probably due to whether the C- or N-terminal fragment of APP was targeted. However, while background labeling with 3 of the antibodies was minimal, there was robust, diffuse labeling of axons due to myelin immunolabeling with the Y188 antibody, which was determined to be specific. Thus, while these antibodies can detect axonal injury with similar efficacy in sheep brains, caution must be taken with Y188 owing to confounding myelin immunolabeling. This study will hopefully serve as a guide for optimal immunodetection of axonal injury in ovine encephalopathies.

While most cases of human muscle-invasive bladder cancer (MIBC) are diagnosed as conventional urothelial carcinoma (UC), there is growing recognition of histologic subtypes and divergent differentiation within conventional UC. In this study, 31 dogs with UC (33 slides) were evaluated for histologic subtypes and divergent differentiation, as specified by the recent World Health Organization update on the classification of urinary bladder cancers. Slides were reviewed by a medical uropathologist and 3 board-certified veterinary pathologists and assessed for expression of uroplakin III, vimentin, and E-cadherin. All tumors were classified as UC. Fifteen cases were identified as conventional UC. Among the remainder, 8 displayed glandular differentiation, 4 were classified as sarcomatoid UC, 2 showed squamous differentiation, 1 case was classified as a large nested subtype, and 1 case was classified as a tubular/microcystic subtype. This study found a higher frequency of certain histologic subtypes and divergent differentiation in canine UC, particularly sarcomatoid UC and UC with glandular differentiation, compared to previous reports of both canine UC and human MIBC. The relatively high prevalence of the sarcomatoid UC and UC with glandular differentiation in dogs observed in this study suggests that canine UC may serve as a valuable translational model for evaluating novel therapeutic agents, particularly for these rare and aggressive subtypes in humans.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an increasingly serious global health issue. The establishment of accurate animal models is crucial for elucidating its pathogenesis and developing effective therapeutic strategies. Although mouse models are widely used in MASLD research, they exhibit significant differences from humans in metabolic traits and disease progression, limiting their ability to fully recapitulate key pathological features of MASLD. In this study, we established an MASLD model in Apodemus peninsulae using a high-fat diet (HFD) and compared it with the commonly used C57BL/6J mouse model. The results showed that A. peninsulae developed marked lipid metabolism disorders and liver function impairment as early as week 4 with an HFD intervention. Histological analysis revealed progressive steatosis, inflammatory infiltration, and early fibrosis from weeks 8 to 16, which was confirmed by oil red O, Masson's trichrome, and Sirius red staining. In contrast, pathological progression in C57Bl/6J mice was slower, with milder fibrosis. Immunolabeling and inflammatory cytokine expression further indicated a more intense inflammatory response in A. peninsulae. Overall, A. peninsulae offers advantages, such as rapid disease induction and stable phenotypes, making it a promising animal model for studying early-stage MASLD. Its shorter modeling period and more pronounced steatosis and liver injury suggest it more closely mimics the early pathological changes seen in human MASLD.

The objective of this study was to evaluate the effect of different fixatives and demineralizers on immunohistochemical (IHC) detection of antigens in bone marrow (BM). Sternal BM samples were collected within 24 hours of death from dogs with spontaneous disease, fixed with acetic acid-zinc-formalin (AZF) or 10% neutral-buffered formalin (NBF) for 24 hours, and decalcified with formic acid, hydrochloric acid, or ethylenediaminetetraacetic acid (EDTA) for 1, 12, or 24 hours, respectively. Immunohistochemical sections for CD3, CD20, CD34, CD204, FLT3, and factor VIII-related antigen (FVIII-rAG) were scored for background, signal intensity, and percent positive cells by 4 independent raters. Some endothelial but not hematopoietic cells were CD34 immunopositive, precluding further assessment. Immunopositive BM cells ranged from 1.3% to 18.3% (CD3), 1.3% to 22.3% (CD20), 0.5% to 22.5% (CD204), and 0% to 17.6% (FLT3). Background scores were similar for all antigens and fixatives except for CD3, for which NBF yielded lower scores than AZF. The signal intensity for all IHC assays was similar for AZF and NBF. The percentage of FLT3- and FVIII-rAG-immunopositive cells was slightly higher in AZF- than NBF-fixed samples. Different demineralizers yielded similar results for all IHC assays except higher background for CD20/EDTA. Signal intensity was higher for CD204 in samples demineralized with EDTA rather than acids. Higher percentages of CD204 and FLT3 immunopositive cells were noted with EDTA relative to acid demineralization. Overall, with the use of stringently standardized pre-analytic and processing protocols, all IHC assays yielded acceptable results, and differences between protocols were considered minor.

Mouse kidney parvovirus (MKPV) causes inclusion body nephropathy, resulting in clinical signs and mortality in immunodeficient mice and subclinical infection in immunocompetent mice. While late-stage renal lesions and viral replication have been characterized, a comprehensive multisystemic investigation of MKPV infection from the initial to the late stages of infection has not been conducted. Our goal was to investigate lesions and viral replication in all major organs at multiple stages of MKPV infection in immunocompetent C57BL/6NCrl (B6) and Crl: CD1(ICR) (CD1) mice and immunodeficient NOD. Cg-Prkdc^scidIl2rg^tm1Wjl/SzJ (NSG) mice. Following experimental oronasal inoculation with MKPV, mice were evaluated at 15 time points from 1.5 to 112 days post-inoculation (DPI) by histology and in situ hybridization for MKPV RNA on all major organs, as well as immunohistochemistry for markers of immune cells and renal tubular injury. In all strains, the gastrointestinal mucosa was the initial site of viral replication beginning at 3 DPI and persisting through the study without associated lesions. In B6 and CD1 mice, viral replication was first detected in renal tubules on 28 and 14 DPI, respectively, and lymphoplasmacytic tubulointerstitial nephritis was first evident on 63 and 49 DPI, respectively. B6 mice displayed the lowest levels of renal viral replication and lesion severity. In contrast, renal viral replication was highest in NSG mice; the virus was first detected on 42 DPI and in association with tubular degeneration from 63 DPI. Electron microscopy on kidney tissues of infected mice revealed parvoviral virions, nuclear replication, and assembly compartments for the first time.

Neuroaxonal dystrophy is a group of genetic neurodegenerative diseases that are histopathologically characterized by swollen axons (spheroids). We previously established a novel rat model of neuroaxonal dystrophy harboring a V95E missense mutation in the heat shock protein family A (HSP70) member 8 (Hspa8) gene that originally emerged by ENU-induced random mutagenesis. Hspa8^V95E mutant rats show marked spheroid formation in the central nervous system and develop progressive hind limb ataxia. However, the detailed pathology of Hspa8^V95E mutant rats remains to be elucidated. In the current study, we examined the characteristics of gait abnormalities and the detailed distribution of spheroids in the central nervous system of Hspa8^V95E knock-in (KI) rats. Using footprint tests, we demonstrated the increased ratio of step width to step length (outward step) of the hind limbs in Hspa8^V95E KI rats from 3 weeks of age. In Hspa8^V95E KI rats aged 15 weeks, spheroids were predominantly distributed in the proprioceptive sensory pathway from the lower body, including the gracile fasciculus and the nucleus. The number of spheroids increased with age and was accompanied by glial reactions in the dorsal funiculus. Moreover, we observed the accumulation of kinesin light chain 1; kinesin heavy chain isoforms 5A, -5B, and -5C; and microtubule-associated protein light chain 3 B in the spheroids and degenerated axons of Hspa8^V95E KI rats at 13 weeks of age. Collectively, our data suggest the involvement of impaired axonal transport and autophagy in spheroid formation in Hspa8^V95E mutant rats.

A 12-year retrospective search identified 106 sheep and goats diagnosed with Clostridium perfringens type D enterotoxemia, and in which the heart was histologically examined. Twenty cases (20/106, 19%), including 10 sheep and 10 goats, had cardiac lesions that were presumed to be associated with enterotoxemia. The lesions included myocardial degeneration and/or necrosis (n = 16, 80%), hemorrhage (n = 17, 85%), and proteinaceous interstitial edema (n = 6, 30%). Myocardial degeneration and/or necrosis was more frequent in goats (10/10, 100%) compared with sheep (6/10, 60%). Hemorrhage was more frequent in sheep (10/10, 100%) compared with goats (7/10, 70%). Myocardial proteinaceous interstitial edema was exclusive to sheep. Cardiac lesions occur in spontaneous cases of C. perfringens type D enterotoxemia in small ruminants and may play a role in the clinical signs and/or the demise of the animal.

Female Hsd:Athymic nude-Foxn1^nu sentinel mice spontaneously develop a life-limiting protein-losing nephropathy. We aimed to characterize this disease and identify risk factors. Affected mice presented with anasarca and pale tan, irregularly pitted kidneys. Histologically, glomeruli were distorted by eosinophilic, hyaline, mesangial deposits. Additional non-specific glomerular changes included synechiae, periglomerular fibrosis, and capillary thrombosis. Ectatic tubules with attenuated epithelium and tubular casts and interstitial inflammation were also present. Mesangial deposits were Congo red (CR)-negative, periodic acid-Schiff-positive, and pale blue to pink using Masson's trichrome stain. The glomerular basement membrane was mildly irregular using Jones' methenamine silver stain. The mesangial deposits were immunoglobulin G (IgG)- and immunoglobulin A (IgA)-immunonegative and immunoglobulin m (IgM)-immunopositive. Ultrastructurally, subendothelial electron-dense deposits were composed of straight and curved linear, 30 to 170 nm diameter tubular, and 9 to 16 nm diameter fibrillary profiles. Together, these findings were consistent with hyaline glomerulopathy due to IgM deposition. Prevalence of the disease over 6 years was 0.6% (75/13 042 homozygous sentinel mice). Vivarium biosecurity level, infectious disease screening results, and comorbidities were evaluated in 75 female, 6-month-old, homozygous nude sentinel mice with hyaline glomerulopathy and 75 without. Neither biosecurity level nor pathogen diversity was risk factors. However, sentinel mice with auto-inflammatory conditions, such as proliferative typhlocolitis (P = .005) and dermatitis (P = .03), and with lymphoid neoplasia (lymphoma; P = .0007) had a lower risk of developing hyaline glomerulopathy. Our results support the diagnosis of hyaline glomerulopathy in young adult, female, nude sentinel mice and help recognize this spontaneous condition in a canonical immunodeficient research model.