Progressive gammopathy and coagulopathy in a young English bulldog.

A restricted polyclonal or biclonal gammopathy resulting in bleeding tendencies was diagnosed in a young, neutered male English bulldog with concurrent splenomegaly, anemia, and severe elevations in IgM and, to a lesser degree, IgA immunoglobulins. There was a positive clinical response to treatment with prednisone and chlorambucil. This case bears similarity to a recently published syndrome of polyclonal gammopathy that is not neoplastic in origin in this breed. Key clinical message: The current case describes the management and clinical course of a recently described syndrome of polyclonal gammopathy in English bulldogs.

Gammapathie et coagulopathie progressives chez un jeune bouledogue Anglais. Une gammapathie polyclonale restreinte ou biclonale résultant en une tendance aux saignements fut diagnostiquée chez un jeune bouledogue Anglais mâle castré, avec une splénomégalie concomitante, de l'anémie et une augmentation sévère des immunoglobulines IgM et, à un degré moindre, des IgA. Une réponse clinique positive au traitement avec de la prednisone et du chlorambucil fut notée. Ce cas comporte des similarités avec un syndrome récemment décrit de gammapathie polyclonale qui ne serait pas d'origine néoplasique chez cette espèce.Message clinique clé :Le présent cas décrit la gestion et l'évolution clinique d'un syndrome récemment décrit de gammapathie polyclonale chez les bouledogues Anglais.(Traduit par Dr Serge Messier).

Diffuse Small B-Cell Lymphoma: A High-Grade Malignancy.

The most common subtype of lymphoma in the dog is diffuse large B-cell lymphoma (DLBCL). The remaining forms of B-cell lymphoma in dogs are categorized as small-to-intermediate in size and include marginal zone, follicular, mantle cell, and small-cell lymphocytic lymphoma. Marginal zone lymphoma and follicular lymphoma have readily identifiable unique histologic features while other forms of small B-cell lymphoma in the dog are poorly described by histopathology. Forty-seven cases of nodal small B-cell lymphoma identified by flow cytometry (small cell size based on forward scatter) with concurrent histopathology were reviewed. These cases fell into 3 histologic subtypes: marginal zone lymphoma, follicular lymphoma, and a diffuse form of small B-cell lymphoma with consistent features. As a descriptive term, we refer to the latter subtype as diffuse small B-cell lymphoma (DSBCL) until it can be further characterized by gene expression profiling and other molecular tools. Clinical presentation of DSBCL was compared to cases of histologically confirmed DLBCL and clinical follow-up was obtained for 22 of the 27 cases of DSBCL. This subset of diffuse small B-cell lymphoma had an overall median survival of 140 days. The expression of CD21, class II MHC and CD25 by flow cytometry did not differ between DSBCL and the other histologic subtypes of small cell B-cell lymphoma making histopathology the only current method of classification.

Delayed diagnosis of fatal pneumonic canine plague: clinical and pathologic features in two naturally infected Colorado dogs.

BACKGROUND: Plague caused by Yersinia pestis is a highly infectious and potentially fatal zoonotic disease that can be spread by wild and domestic animals. In endemic areas of the northern hemisphere plague typically cycles from March to October, when flea vectors are active. Clinical forms of disease include bubonic, septicemic, and pneumonic plague. All clinical forms are uncommon in dogs and the pneumonic form is exceedingly rare. CASE PRESENTATION: Two mixed breed young-adult male domestic dogs presented to Colorado veterinarians with fever and vague signs that progressed to hemoptysis within 24 h. Case 1 presented in June 2014, while Case 2 occurred in December 2017. Thoracic radiography of Case 1 and 2 revealed right dorsal and right accessory lobe consolidation, respectively. In Case 1 initial differential diagnoses included pulmonary contusion due to trauma or diphacinone toxicosis. Case 1 was euthanized ~ 24 h post presentation due to progressive dyspnea and hemoptysis. Plague was confirmed 9 days later, after the dog's owner was hospitalized with pneumonia. Case 2 was treated as foreign body/aspiration pneumonia and underwent lung lobectomy at a veterinary teaching hospital. Case 2 was euthanized after 5 days of hospitalization when bacterial culture of the excised lobe yielded Yersinia pestis. Both dogs had severe diffuse necrohemorrhagic and suppurative pneumonia at post mortem examination. CONCLUSIONS: Both dogs were misdiagnosed due to the atypical lobar presentation of an extremely rare form of plague in a species that infrequently succumbs to clinical disease. Presentation outside of the typical transmission period of plague was also a factor leading to delayed diagnosis in Case 2. Erroneous identification by automated bacterial identification systems was problematic in both cases. In endemic areas, plague should be ruled out early in febrile dogs with acute respiratory signs, hemoptysis, lobar or diffuse pathology, and potential for exposure, regardless of season. Seasonal and geographic distributions of plague may shift with climate change, so vigilance by primary care veterinarians is warranted. Timely submission of samples to a veterinary diagnostic laboratory could expedite accurate diagnosis and reduce potential for human and domestic animal exposure.

Clinical features of canine nodal T-cell lymphomas classified as CD8+ or CD4-CD8- by flow cytometry.

Canine T-cell lymphoma (TCL) encompasses a heterogeneous group of diseases with variable clinical presentation, cytomorphology, immunophenotype, and biologic behaviour. The most common types of TCL in dogs involving peripheral lymph nodes include indolent T-zone lymphoma (TZL) and biologically aggressive peripheral T-cell lymphoma (PTCL). TCL phenotypes can be categorized by expression of the surface antigen molecules CD4 and CD8. The majority of TCL cases are CD4+ , with far fewer cases being CD8+ or CD4- CD8- . The clinical features of CD4+ TCLs have been previously described. The less common TCL phenotypes, however, are poorly characterized with little to no information about prognosis. In this retrospective study, we describe and correlate the presenting clinical signs, flow cytometry, and outcomes of 119 dogs diagnosed with nodal, non-TZL, CD8+ or CD4- CD8- TCL by flow cytometry. Skin lesions present at the time of diagnosis were more commonly observed in the CD8+ TCL group. Mediastinal enlargement and/or hypercalcemia were more commonly seen in the CD4- CD8- TCL group. Dogs with either CD8+ or CD4- CD8- TCLs had aggressive clinical disease with median overall survival (OS) times of 198 days and 145 days, respectively. In both groups, neoplastic cell size determined by flow cytometry ranged from small to large, and large cell size was associated with shorter OS times (median OS = 61 days). Cases classified as small cell had a median OS of 257 days. Expression levels of major histocompatibility complex (MHC) class II and CD5 were highly variable among cases but were not prognostically significant in this group of patients.

Ultrasonographic features of mesenteric cysticercosis in a domestic rabbit (Oryctolagus cuniculus).

A 5-year-old, 0.92-kg (2-lb), spayed female Dwarf Hotot rabbit was evaluated for a 1-day duration of lethargy and anorexia. Survey radiographs revealed evidence of gastrointestinal stasis. Abdominal ultrasonography characterized multiple small, round, anechoic structures embedded in the mesentery. These structures were thin walled with hyperechoic strands/septations. Most of the structures contained a well-defined, eccentric, hyperechoic nodule adherent to the intraluminal wall. Mesenteric cysticercosis was confirmed via exploratory laparotomy and histopathology. To the authors' knowledge, this is the first description of the ultrasonographic features of mesenteric cysticercosis in a domestic rabbit.

Canine CD4+ T-cell lymphoma identified by flow cytometry exhibits a consistent histomorphology and gene expression profile.

T-cell lymphomas (TCL) are a diverse group of neoplasms with variable diagnostic features, pathophysiologies, therapeutic responses and clinical outcomes. In dogs, TCL includes indolent and aggressive tumours such as T-zone lymphoma (TZL) and peripheral T-cell lymphoma (PTCL), respectively. Delineation of molecular subtypes and investigation into underlying pathophysiologies of aggressive TCLs remains inadequate. We investigate the correlations between flow cytometry and histopathology of 73 cases of nodal TCL. The majority of cases (82.2%) were characterized as CD4+ TCL by flow cytometry. Fewer cases were classified as CD8+ TCL (6.8%) or CD4- CD8- TCL (11.0%). All cases, regardless of immunophenotype, exhibited conserved histologic features consistent with the WHO classification of PTCL. Histologic subsets of PTCL corresponding to immunophenotypic features were not identified. Neoplastic cell size determined by flow cytometry correlated significantly with mitotic rate. RNA-seq was performed on a subset of CD4+ PTCL cases (n = 6) and compared with sorted control CD4+ T-cells. The gene expression pattern of CD4+ PTCL was similar between all cases regardless of breed. PTCL was enriched in pathways representing G-coupled protein receptor signalling, extracellular matrix remodelling and vascular development, immune signalling and mitotic activity. Furthermore, global gene expression changes were consistent with downregulation of PTEN signalling and upregulation of the MTOR-PI3K-ATK axis. In this study, we evaluated the correlations between flow cytometry, histopathology and gene expression within a large cohort of nodal TCLs. We further demonstrate the ability of flow cytometry to identify a subtype of T-cell lymphoma, CD4+ PTCL, with a uniform histomorphology and gene expression profile.

Glucose metabolism impacts the spatiotemporal onset and magnitude of HSC induction in vivo.

Many pathways regulating blood formation have been elucidated, yet how each coordinates with embryonic biophysiology to modulate the spatiotemporal production of hematopoietic stem cells (HSCs) is currently unresolved. Here, we report that glucose metabolism impacts the onset and magnitude of HSC induction in vivo. In zebrafish, transient elevations in physiological glucose levels elicited dose-dependent effects on HSC development, including enhanced runx1 expression and hematopoietic cluster formation in the aorta-gonad-mesonephros region; embryonic-to-adult transplantation studies confirmed glucose increased functional HSCs. Glucose uptake was required to mediate the enhancement in HSC development; likewise, metabolic inhibitors diminished nascent HSC production and reversed glucose-mediated effects on HSCs. Increased glucose metabolism preferentially impacted hematopoietic and vascular targets, as determined by gene expression analysis, through mitochondrial-derived reactive oxygen species (ROS)-mediated stimulation of hypoxia-inducible factor 1α (hif1α). Epistasis assays demonstrated that hif1α regulates HSC formation in vivo and mediates the dose-dependent effects of glucose metabolism on the timing and magnitude of HSC production. We propose that this fundamental metabolic-sensing mechanism enables the embryo to respond to changes in environmental energy input and adjust hematopoietic output to maintain embryonic growth and ensure viability.

Functional analysis of TaABF1 during abscisic acid and gibberellin signalling in aleurone cells of cereal grains.

The wheat transcription factor TaABF1 physically interacts with the protein kinase PKABA1 and mediates both abscisic acid (ABA)-induced and ABA-suppressed gene expression. In bombarded aleurone cells of imbibing grains, the effect of TaABF1 in down-regulating the gibberellin (GA)-induced Amy32b promoter was stronger in the presence of exogenous ABA. As these grains contained low levels of endogenous ABA, the effect of TaABF1 may also be mediated by ABA-induced activation even in the absence of exogenous ABA. Levels of TaABF1 protein decreased slightly during imbibition of afterripened grains. However, TaABF1 levels (especially in aleurone layers) were not substantially affected by exogenous ABA or GA, indicating that changes in TaABF1 protein level are not an important part of regulating its role in hormone signalling. We found that TaABF1 was phosphorylated in vivo in aleurone cells, suggesting a role for post-translational modification in regulating TaABF1 activity. Induction of Amy32b by overexpression of the transcription factor GAMyb could not be prevented by TaABF1, indicating that TaABF1 acts upstream of GAMyb transcription in the signalling pathway. Supporting this view, knockdown of TaABF1 by RNA interference resulted in increased expression from the GAMyb promoter. These results are consistent with a model in which TaABF1 is constitutively present in aleurone cells, while its ability to down-regulate GAMyb is regulated in response to ABA.