Background
Bedlington terrier copper toxicosis (CT) is due to a homozygous exon deletion in COMMD1. CT also occurs in Bedlingtons lacking this deletion. An association with two ABCA12 single ...nuceotide polymorphism (SNP) splice variants was reported. Labrador retriever CT is associated with a missense mutation in ATP7B, and with a protective mutation in ATP7A.
Methods
Liver and DNA samples from 24 affected and 10 unaffected Bedlingtons were assessed for copper and genetic variants. Allelic frequencies were compared. The ATP7B mutation frequency was investigated in 144 dogs of other breeds.
Results
The ABCA12 SNPs showed no differences between groups. The COMMD1 deletion was less frequent in unaffected than in affected dogs and in affected dogs post‐2001 than pre‐2001. The ATP7B mutation was more frequent in affected than unaffected Bedlingtons. Thirty‐five of 144 dogs of other breeds were homo‐ or heterozygous for the ATP7B mutation. The ATP7A mutation was absent from Bedlingtons.
Limitations
Clinical information and qualitative copper measurements were unavailable for most dogs.
Conclusion
The COMMD1 deletion remains present in Bedlington terriers but is no longer the primary cause of CT. ABCA12 SNPs were not associated with CT. The ATP7B:c.4358G>A mutation was significantly associated with Bedlington CT and was more common in dogs of this breed than in the 144 dogs of other breeds.
Background
Copper‐associated chronic hepatitis (CuCH) is poorly characterised in Cavalier King Charles spaniels (CKCS).
Methods
Hepatic copper accumulation was qualitatively and quantitatively ...assessed, and blood samples were used for genetic testing to screen for known CuCH‐associated genetic variants.
Results
The study included 13 CKCS with CuCH and eight unaffected controls. Increased transaminase activities, elevated biliary enzyme concentrations and portal hypertension were documented in 100%, 73% and 38% of dogs with CuCH, respectively. Five dogs had three or more abnormalities in measures of liver function. All 11 dogs with CuCh that underwent genetic testing were homozygous negative for the COMMD1 deletion and ATP7A variant but homozygous positive (n = 7) or heterozygous (n = 4) for the ATP7B variant. Liver histology often demonstrated marked architectural distortion by severe, bridging fibrosis and regenerative nodules with lymphoplasmacytic inflammation. Centrilobular copper accumulation characterised early cases with minimal fibrosis. When fibrosis was significant, copper was often differentially concentrated within regenerative nodules. Chelation therapy resolved laboratory derangements and portal hypertension in five of seven dogs. Of the 7 non‐surviving dogs with CuCH, 6 had not received chelation therapy.
Limitations
Limitations include a small cohort size and the lack of pedigree analyses to corroborate heritability.
Conclusions
CuCH should be considered in CKCS with suspected liver disease. Long‐term prognosis seems favourable in dogs receiving chelation therapy, notwithstanding the presence of previously reported negative prognostic markers.
COVID-19, caused by SARS-CoV-2 virus, emerged as a pandemic disease posing a severe threat to global health. To date, sporadic studies have demonstrated that innate immune mechanisms, specifically ...neutrophilia, NETosis, and neutrophil-associated cytokine responses, are involved in COVID-19 pathogenesis; however, our understanding of the exact nature of this aspect of host-pathogen interaction is limited. Here, we present a detailed dissection of the features and functional profiles of neutrophils, dendritic cells, and monocytes in COVID-19. We portray the crucial role of neutrophils as drivers of hyperinflammation associated with COVID-19 disease via the shift towards their immature forms, enhanced degranulation, cytokine production, and augmented interferon responses. We demonstrate the impaired functionality of COVID-19 dendritic cells and monocytes, particularly their low expression of maturation markers, increased PD-L1 levels, and their inability to upregulate phenotype upon stimulation. In summary, our work highlights important data that prompt further research, as therapeutic targeting of neutrophils and their associated products may hold the potential to reduce the severity of COVID-19.
A 2‐year‐old, male, neutered labrador retriever with a previous diagnosis of left renal agenesis and left cryptorchidism presented for investigation of mild intermittent urinary incontinence. ...Abdominal ultrasound, intravenous urography and retrograde positive‐contrast urethrocystography were performed, identifying an unusual fluid‐filled structure, confluent with the left side of the prostate gland. Histopathological diagnosis, following surgical excision, was an ectopic ureterocoele remnant. Urinary incontinence temporarily improved following surgery, but subsequently recurred. A presumptive diagnosis of urethral sphincter mechanism incompetence, in addition to the ectopic ureterocoele remnant was given. Dogs with renal agenesis typically have an absent ipsilateral ureter; however, this report demonstrates an ipsilateral ectopic ureterocoele remnant, a condition rarely reported in veterinary medicine. Multiple ipsilateral genitourinary deformities should be suspected and investigated in animals presenting with any urogenital developmental abnormality. Clinical significance of ectopic ureterocoele remnant in male dogs with urinary incontinence should however be carefully evaluated, and other causes (e.g., urethral sphincter mechanism incompetence) should be considered.
Background
The cytologic diagnosis of inflammation on canine hepatic aspirates can be confounded by neutrophilic infiltrates in the liver of dogs with nodular regeneration, by extramedullary ...hematopoiesis, and by marked blood contamination.
Objectives
We aimed to assess the association between neutrophil counts on hepatic cytology and the histopathologic diagnosis in dogs with hepatitis and non‐inflammatory hepatopathy. We also sought to determine a cut‐off value for the cytologic diagnosis of hepatitis.
Methods
In a retrospective blinded pilot study, three observers independently reviewed hepatic aspirates that had corresponding histopathologic examinations performed within 2 days. The number of neutrophils per 200 hepatocytes was determined and averaged among observers. Only neutrophils within or directly in contact with a cluster of ≥5 hepatocytes were counted, and only intact hepatocytes within an approximate monolayer were included. Data are presented as the median (range), and the Mann‐Whitney U test is used to make comparisons between groups.
Results
Eighteen cases were included (13 hepatitis and five vacuolar hepatopathy). Aspirates with a histopathologic diagnosis of hepatitis had increased numbers of neutrophils compared with those of vacuolar hepatopathy (7.7 0.3‐18.3 vs 3.0 1.0‐5.3; P = .038). Receiver operating characteristic curve analysis indicated that ≥6 neutrophils were 61.5% (CI 31.6%‐86.1%) sensitive and 100% (CI 47.8%‐100%) specific for identifying hepatitis.
Conclusions
Liver aspirates from hepatitis cases have a higher number of neutrophils on cytology compared with those from vacuolar hepatopathy; however, larger studies, including those with dogs with other liver pathologies, are required. Identification of six or more neutrophils per 200 hepatocytes is highly suggestive of hepatitis.
Diffuse large B‐cell lymphoma (DLBCL) is the most common haematopoietic tumour in dogs and recognized as clinical model for its human counterpart. Recently, neutrophil‐to‐lymphocyte (NLR) and ...lymphocyte‐to‐monocyte (LMR) ratios have been shown to predict time‐to‐progression (TTP) and lymphoma‐specific survival (LSS) in dogs with DLBCL treated with CHOP‐based chemotherapy. We retrospectively evaluated in 59 dogs diagnosed with DLBCL the prognostic value of haematological parameters and derived ratios: NLR, LMR, platelet‐to‐lymphocyte (PLR) and platelet‐to‐neutrophil (PNR) ratios for TTP, LSS and associated secondary end‐points (time‐to‐progression‐rate TTPR and lymphoma‐specific survival‐rate LSSR) as rates at 180 and 365 days. PNR is an independent prognostic marker (p ≤ .001) for TTPR/180 and 365 days, dogs with a PNR above 0.032 were more likely to progress before 180 days (sensitivity 46.5%, specificity 87.5%, p = .004). On univariate analysis, NLR showed a prognostic significance for LSSR/180 (p = .006) and LSSR/365 (p = .009). A baseline NLR value below 7.45 was positively associated with survival at 180 days (sensitivity 52%, specificity 85.3%, p = .025). The presence of substage b, was associated with early progression and decreased survival at 180 days (p = .031). Anaemia significantly reduced LSSR at 365 days (p = .028). This is the first study evaluating PLR and PNR in canine DLBCL and demonstrates that PNR could be a predictor of early lymphoma progression. Since peripheral blood cell composition can be affected by several non‐oncological causes, the development of larger multicenter studies with homogeneous inclusion criteria could help to better determine the true predictive values of blood cell ratios in dogs' DLBCL treated with CHOP chemotherapy.
Both the spindle microtubule-organizing centers and the nuclear pore complexes (NPCs) are convoluted structures where many signaling pathways converge to coordinate key events during cell division. ...Interestingly, despite their distinct molecular conformation and overall functions, these structures share common components and collaborate in the regulation of essential processes. We have established a new link between microtubule-organizing centers and nuclear pores in budding yeast by unveiling an interaction between the Bfa1/Bub2 complex, a mitotic exit inhibitor that localizes on the spindle pole bodies, and the Nup159 nucleoporin. Bfa1/Bub2 association with Nup159 is reduced in metaphase to not interfere with proper spindle positioning. However, their interaction is stimulated in anaphase and assists the Nup159-dependent autophagy pathway. The asymmetric localization of Bfa1/Bub2 during mitosis raises the possibility that its interaction with Nup159 could differentially promote Nup159-mediated autophagic processes, which might be relevant for the maintenance of the replicative lifespan.
Medullary striations (MS) have been anecdotally observed on ultrasound of feline kidneys; however, their significance is unknown. Aims of this retrospective, case control, pilot study were to ...describe the appearance, prevalence, and clinicopathological correlates of MS in a referral feline population. Still images from 1247 feline abdominal ultrasound studies performed between 2011 and 2021 were reviewed. Cats with MS were identified and compared with age‐matched controls. Serum urea, creatinine, calcium, phosphate, and calcium‐phosphate‐product, plus urine specific gravity, urine protein: creatinine ratio (UPC), prevalence of active sediment (defined as > 5 red (RBC) or white blood cells (WBC) per high‐power field) and prevalence of positive urine culture were compared between MS and control groups using the Mann–Whitney U test or Fisher's Exact test. Data are presented as median range. 27 cats were identified as having MS, giving a prevalence of 2.2% with a significantly higher proportion being seen in males (P = 0.018). Medullary striation cats had significantly higher UPC values than controls (0.46 0.16–7.57 vs. 0.16 0.07–2.27; P = 0.006). Cats with MS were more likely to have active urinary sediments (39% vs 8%, P = 0.023), but no difference in prevalence of positive urinary cultures was observed between groups. There was no significant difference in other parameters between MS and control cats. Renal histopathology performed in three MS cats revealed focal regions of linear medullary fibrosis. Medullary striations are associated with proteinuria and urinary tract inflammation in cats, which may reflect renal tubular dysfunction and/or inflammation. Hence identification might allow for earlier detection of renal pathology.
The diagnostic criteria for IgG4‐RD in humans remain a matter of discussion, but usually rely on typical clinical features of autoimmune disease in multiple organs combined with characteristic ...histological features or, in the absence of biopsy samples, increased circulating IgG4 concentration and an effective response to glucocorticotherapy. ...a diagnosis cannot be made on the basis of increased serum concentration of IgG4 alone. Confirmation of increased serum IgG4 concentrations in this paper used an as yet unpublished immunofixation technique based on the use of a commercial polyclonal canine anti‐IgG1 antibody which is suggested to cross‐react with canine IgG4. Because measurement of canine IgG subclasses is problematic in the absence of commercially available reagents, we look forward to the publication of this new study.
Background
Reports of chronic hepatitis in dogs caused by Leptospira spp. are confined to small case series. Fluorescence in situ hybridization (FISH) allows the identification of spirochetes in ...liver samples. Consequently, this technique may help elucidate the role of Leptospira spp. in cases of chronic hepatitis.
Objectives
To describe cases of hepatic leptospirosis in dogs diagnosed by FISH and subsequent polymerase chain reaction (PCR) speciation, with the absence of clinically relevant renal involvement.
Animals
Ten client‐owned dogs.
Methods
Retrospective case series from the University of Cambridge presented between 2013 and 2016 or cases consulted by telephone advice during this time period. Cases were selected based on histopathologically confirmed granulomatous hepatitis and leptospiral organisms identified by FISH and PCR speciation (Leptospira interrogans/kirschneri).
Results
All cases had increased liver enzyme activities, and FISH in combination with PCR speciation‐confirmed infection with L. interrogans/kirschneri. Four dogs underwent repeat liver biopsy, FISH and PCR speciation 4‐15 months after initial presentation and doxycycline treatment with 1 dog undergoing repeat sampling at necropsy. Three dogs that underwent repeat biopsy remained positive for L. interrogans/kirschneri infection. Six dogs were alive at the time of manuscript preparation and 4 dogs were euthanized as a result of progressive liver disease.
Conclusions and Clinical Importance
The presence of hepatic leptospiral organisms may be associated with chronic granulomatous hepatitis without clinical evidence of renal involvement. Further studies are necessary to elucidate the etiological role of these organisms in the disease.
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