Oliver A Garden

• BSc BVetMed PhD DACVIM DECVIM
• Dean of School at Louisiana State University

OBJECTIVE The primary objective was to identify veterinary workforce characteristics and factors contributing to staying in or leaving a veterinary practice. A secondary objective was to compare workforce characteristics and factors related to retention between survey respondents working in rural versus nonrural areas. METHODS Veterinarians were s...

Regulatory T (Treg) cells are essential for the maintenance of immunological tolerance, yet the molecular components required for their maintenance and effector functions remain incompletely defined. Inactivation of VPS34 in Treg cells led to an early, lethal phenotype, with massive effector T cell activation and inflammation, like mice lacking Tre...

Management of immune thrombocytopenia (ITP) in dogs and cats is evolving, but there are no evidence‐based guidelines to assist clinicians with treatment decisions. Likewise, the overall goals for treatment of ITP have not been established. Immunosuppressive doses of glucocorticoids are the first line treatment, but optimal treatment regimens beyond...

Immune thrombocytopenia (ITP) is the most common acquired primary hemostatic disorder in dogs. Immune thrombocytopenia less commonly affects cats but is an important cause of mortality and treatment‐associated morbidity in both species. Immune thrombocytopenia remains a diagnosis of exclusion for which diagnostic guidelines are lacking. Primary, or...

Regulatory T (Treg) cells are essential for the maintenance of immunological tolerance, yet the molecular components required for their maintenance and effector functions remain incompletely defined. Inactivation of VPS34 in Treg cells led to an early, lethal phenotype, with massive effector T cell activation and inflammation, like mice lacking Tre...

Background The dog is the most popular companion animal and is a valuable large animal model for several human diseases. Canine immune-mediated hematological diseases, including immune-mediated hemolytic anemia (IMHA) and immune thrombocytopenia (ITP), share many features in common with autoimmune hematological diseases of humans. The gut microbiom...

Background While immune checkpoint inhibitors (ICIs) have been revolutionary in the treatment of cancer, their administration has been associated with a variety of immune-related adverse events (irAEs), including myasthenia gravis (MG), and Lambert-Eaton myasthenic syndrome (LEMS). Objective To provide a comprehensive synthesis of the evidence sup...

Regenerative therapies aimed at replacing photoreceptors are a promising approach for the treatment of otherwise incurable causes of blindness. However, such therapies still face significant hurdles, including the need to improve subretinal delivery and long-term survival rate of transplanted cells, and promote sufficient integration into the host...

Induction of remission is easily achieved with dietary treatment in dogs diagnosed with Food Responsive Chronic Diarrhea (FRD). Administration of prebiotics and glycosaminoglycans (GAGs) may improve epithelial cell integrity and therefore be useful as adjunct treatment. This study evaluated whether the relapse rate of FRD dogs that are switched bac...

Background Factors known to be associated with outcome of acquired myasthenia gravis (MG) in dogs are limited. Hypothesis/Objectives Of dogs with MG, advancing age and comorbid neoplasia are associated with poor long‐term prognosis and low rates of remission. Animals Ninety‐four client‐owned dogs with MG diagnosed by acetylcholine receptor antibo...

Background: Myasthenia gravis (MG) is an autoimmune disorder of unknown etiology in most patients, in which autoantibodies target components of neuromuscular junctions and impair nerve to muscle transmission. Objective: To provide a synthesis of the evidence examining infectious agents associated with the onset of MG. Hypothesis: We hypothesized th...

Induction of remission is easily achieved with dietary treatment in dogs diagnosed with Food Responsive Chronic Enteropathy (FRD). Administration of prebiotics and glycosaminoglycans (GAGs) may improve epithelial cell integrity and therefore be useful as adjunct treatment. This study evaluated whether the relapse rate of FRD dogs that are switched...

Anesthetics may worsen the outcome of patients undergoing oncologic surgery via immune suppression. This study examines the impact of propofol, ketamine, and alfaxalone on canine peripheral blood lymphocyte (PBL) cytotoxic function in vitro. PBLs isolated from healthy canine blood were cultured in the presence or absence of alfaxalone, propofol, ke...

Background: Mycophenolic acid (MPA) is a broad-acting immunomodulating agent that may be therapeutically beneficial for the treatment of immune-mediated diseases in canine patients. Objectives: To determine the suppressive effects of MPA on T-cell proliferation, and to assess the feasibility of a canine-specific q24 h modified-release MPA formulati...

Myasthenia gravis (MG) is a T cell-dependent, B cell-mediated autoimmune disease. Little is known about its cellular pathogenesis in dogs. This study provides the first preliminary assessment of the frequency of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) in the peripheral blood of dogs with seropositive generalized MG....

Myasthenia gravis (MG) is a T cell-dependent, B-cell mediated autoimmune disease caused by antibodies against the nicotinic acetylcholine receptor or other components of the post-synaptic muscle endplate at the neuromuscular junction. These specific antibodies serve as excellent biomarkers for diagnosis, but do not adequately substitute for clinica...

Canine inflammatory bowel disease (IBD) is a chronic, immunologically mediated intestinal disorder, resulting from the complex interaction of genetic, environmental and immune factors. Hydrolyzed diets are used in dogs with food-responsive diarrhea (FRD) to reduce adverse responses to immunostimulatory proteins. Prebiotics (PRBs) and glycosaminogly...

Class I PI3K enzymes are critical for the maintenance of effective immunity. In T cells, PI3Kα and PI3Kδ are activated by the TCR and costimulatory receptors, whereas PI3Kγ is activated by G protein-coupled chemokine receptors. PI3Kδ is a key regulator of regulatory T (Treg) cell function. PI3K isoform-selective inhibitors are in development for th...

Gene expression profiling has revealed molecular heterogeneity of diffuse large B cell lymphoma (DLBCL) in both humans and dogs. Two DLBCL subtypes based on cell of origin are generally recognized, germinal center B (GCB)-like and activated B cell (ABC)-like. A pilot study to characterize the transcriptomic phenotype of 11 dogs with multicentric BC...

Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) are implicated in the progression and outcome of a variety of pathological states, from cancer to infection. Our previous work has identified three antimicrobial peptides differentially expressed by PMN-MDSCs compared to conventional neutrophils isolated from dogs, mice, and human patie...

Regulatory T cells (Tregs) are a double-edged regulator of the immune system. Aberrations of Tregs correlate with pathogenesis of inflammatory, autoimmune and neoplastic disorders. Phenotypically and functionally distinct subsets of Tregs have been identified in humans and mice on the basis of their extensive portfolios of monoclonal antibodies (mA...

Methods A randomised non-blinded non-inferiority trial was conducted to determine whether treatment with an unfractionated regimen of oral prednisolone was inferior to a fractionated regimen for dogs with primary immune-mediated haemolytic anaemia. Dogs received the same total daily dose of prednisolone as unfractionated (group 1, starting at 4 mg/...

Immune‐mediated hemolytic anemia (IMHA) causes severe anemia in dogs and is associated with considerable morbidity and mortality. Treatment with various immunosuppressive and antithrombotic drugs has been described anecdotally and in previous studies, but little consensus exists among veterinarians as to the optimal regimen to employ and maintain a...

Myeloid-derived suppressor cells (MDSCs) are key players in immune evasion, tumor progression and metastasis. MDSCs accumulate under various pathological states and fall into two functionally and phenotypically distinct subsets that have been identified in humans and mice: polymorphonuclear (PMN)-MDSCs and monocytic (M)-MDSCs. As dogs are an excell...

Immune‐mediated hemolytic anemia (IMHA) is an important cause of morbidity and mortality in dogs. IMHA also occurs in cats, although less commonly. IMHA is considered secondary when it can be attributed to an underlying disease, and as primary (idiopathic) if no cause is found. Eliminating diseases that cause IMHA may attenuate or stop immune‐media...

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Mycophenolic acid (MPA), a noncompetitive, selective and reversible inhibitor of inosine 5′‐monophosphate dehydrogenase (IMPDH), is an immunosuppressive agent that has a long history in medicine. Mechanistically, the inhibition of IMPDH leads to the selective and eventual arrest of T‐ and B‐lymphocyte proliferation. Mycophenolate mofetil (MMF), the...

Comparative oncology is poised to have a far-reaching impact on both animals and human beings with cancer. The field is gaining momentum and has repeatedly proven its utility in various aspects of oncology, including study of the genetics, development, progression, immunology and therapy of cancer. Companion animals provide many advantages over bot...

Objective: To characterize the immune cells present in different forms of feline anterior uveitis. Samples: Eyes were obtained from 49 cats diagnosed with chronic idiopathic lymphoplasmacytic anterior uveitis, 7 cats with feline infectious peritonitis (FIP), and 9 cats euthanized for nonocular disease. Methods: H&E sections were scored on the...

Anaplastic large-cell lymphoma or null-cell lymphoma is a clinical entity reported in people, classified according to the unique appearance of large pleomorphic cells that express CD30. Null-cell lymphoma has also been described in dogs when neither CD3 nor CD79α is expressed by the tumor. We describe a case of lymphoma in the dog in which neoplast...

Background: Paroxysmal gluten-sensitive dyskinesia (PGSD) in border terriers (BTs) results from an immunologic response directed against transglutaminase (TG)2 and gliadin. Recent evidence suggests that PGSD is only one aspect of a range of possible manifestations of gluten sensitivity in the breed. Hypothesis/objectives: Gluten sensitivity in B...

Video 1. A Border terrier with the typical signs expected with paroxysmal dyskinesia (PD). Note the low frequency involuntary muscle contractions in the limbs whilst the dog maintains awareness.

Video 2. Demonstrates the typical clinical signs of a generalized tonic‐clonic seizure (GTCS). Note the high frequency paddling movements in all four legs and loss of consciousness.

Canine lymphoma is a heterogeneous group of diseases and many previous studies have evaluated the response of a mixed population of lymphoma cases to one specific treatment protocol. The aim of this retrospective study was to describe the outcome and prognostic factors in 42 cases of multicentric centroblastic diffuse large B-cell lymphoma treated...

Diffuse large B-cell lymphoma (DLBCL) is the most common type of canine lymphoma and survival times are currently <1 year. Manipulation of the tumour microenvironment, of which the regulatory T cell (Treg) is a principal player, represents a potentially exciting way to curb the rapid proliferation of neoplastic cells. Tregs, characterized by the st...

Case summary A 15-year-old female cat was presented for investigation of progressive behavioural changes, polyuria, polydipsia and periuria. An ovarian granulosa cell tumour was identified and the cat underwent therapeutic ovariohysterectomy (OHE). The cat’s clinical signs resolved, but 6 months later it was diagnosed as having an anaplastic astroc...

Monocytes are key cells of the innate immune system. Their phenotypic and functional roles have been investigated in humans, mice and other animals, such as the rat, pig and cow. To date, detailed phenotypic analysis of monocytes has not been undertaken in dogs. Two important surface markers in human monocytes are CD14 and MHC class II (MHC II). By...

Background: Immune-mediated haemolytic anaemia (IMHA) is reported to be the most common autoimmune disease of dogs, resulting in significant morbidity and mortality in affected animals. Haemolysis is caused by the action of autoantibodies, but the immunological changes that result in their production have not been elucidated. Aims: To investigat...

Antibody clones used for flow cytometry. (DOCX)

Details of primers used for reverse transcription polymerase chain reactions. All primers were obtained from ThermoFisher Scientific. (DOCX)

Spreadsheet of data obtained in this study. (XLSX)

Loading of variables onto components extracted from principal component analysis (n = 16 dogs). Loading scores indicate the strength of correlation, either positive or negative, between individual variables and the components extracted in this model, and these correlations are also represented using the colours shown in the key. Strong positive (>0...

Helper T cell development and function must be tightly regulated to induce an appropriate immune response that eliminates specific pathogens yet prevents autoimmunity. Many approaches involving different model organisms have been utilized to understand the mechanisms controlling helper T cell development and function. However, studies using mouse m...

Paroxysmal gluten-sensitive dyskinesia (previously termed canine epileptoid cramping syndrome) is a condition of Border terriers in which the leading manifestation is neurological. The authors describe a case they believe to represent the first report of a Border terrier with a combination of neurological signs, atopy, positive serological results...

Feline oral squamous cell carcinoma (FOSCC) is an aggressive neoplasm in cats. Little is known about the possible molecular mechanisms that may be involved in the initiation, maintenance and progression of FOSCC. Wnt signalling is critical in development and disease, including many mammalian cancers. In this study, we have investigated the expressi...

Dot plots of the distribution of quantitative signal for DAB for each antibody used in this study. Total area (TA, see Materials and Methods) for the DAB signal Control (normal) and Malignant (tumor) is shown. (TIF)

True positive and true negative rates for putative FOSCC discriminatory markers from ROC curve analysis. Operating characteristics Sensitivity and 1-Specificity of the area fraction values for Cyclin D1, c-Myc and FRA1 at a specific value (Criteria >) calculated using ROC curves. AUC = area under the curve. An AUC of >0.7 is considered to provide a...

Feline tissue arrays were constructed as described in Materials and Methods. Blocks were arrayed with feline tissue samples and also with some human tissue samples for identification. The three slides used in this study (A, B and C) are stained with Haematoxylin & Eosin stain and scanned using a Hamamtsu Nanozoomer scanner are shown here. The origi...

A feline tissue array showing expression of CD1. (A) The DAB stained slides were scanned using a Hamamtsu Nanozoomer scanner are shown here. The original Nanozoomer (ndpi) files were imaged using the NDPI.view2 software. at a higher resolution (1300 x 1300 pixels) than shown; these higher resolution images were used for quantitative analysis as des...

Examples of the histopathological analysis are shown here. Tumor tissue is circled in black and inflammation in red. Present with a multifocal to coalescing pattern is a locally infiltrative, densely cellular neoplastic mass that infiltrates the surrounding stroma. Neoplastic cells are arranged in islands and sheets, within which they exhibit varia...

An example of the process (e.g. concentration, pH etc) used to optimize the antibodies used in this study in feline tissue. Images were acquired at 10x using a standard bright field microscope. The antibodies were coded (AA xx, A to D) and the experimenters blinded to their identity; negative controls without primary antibodies were used (E). Cross...

ß-catenin (used at 1:100 dilution, Cy3-green) expression within the nucleus (stained blue with a DAPI counterstain) was measured in control normal and malignant (FOSSC) feline tissue. Tissue cores were imaged using a Zeiss Axioscan Z.1 slide scanner (Carl Zeiss) with a 40x magnification. Localisation of ß -catenin within the nucleus was measured on...

Diagnostic methods used in the initial and post-treatment evaluation of canine lymphoma are heterogeneous and can vary within countries and institutions. Accurate reporting of clinical stage and response assessment is crucial in determining the treatment efficacy and predicting prognosis. This study comprises a systematic review of all available ca...

Hypoxia and regulatory T cells (Tregs) in tumours are both known to be negative prognostic factors in cancer, and this study demonstrated a correlation between the two factors in canine neoplasia. Samples of 57 canine tumours and 29 canine lymph nodes categorized as tumour-draining, with or without metastasis, or reactive and not tumour-associated,...

MicroRNAs (miRNAs) regulate many aspects of helper T cell (Th) development and function. Here we found they are required for suppression of interleukin-9 (IL-9) expression in Th9 cells and other Th subsets. Two highly related miRNAs (miR-15b and miR-16) that we previously found to play an important role in regulatory T cell (Treg) differentiation w...

Background: Flow cytometry (FC) is assuming increasing importance in diagnosis in veterinary oncology. The European Canine Lymphoma Network (ECLN) is an international cooperation of different institutions working on canine lymphoma diagnosis and therapy. The ECLN panel of experts on FC has defined the issue of reporting FC on canine lymphoma and l...

Background: Corticosteroid treatment is commonly required in veterinary patients for treatment of inflammatory, immune-mediated, neurologic, and neoplastic diseases, which also may require assisted enteral nutrition via percutaneous endoscopic gastrostomy (PEG). Objective: To evaluate complications associated with PEG use in dogs and cats receiv...

The Forkhead box transcription factor FoxP3 is pivotal to the development and function of regulatory T cells (Tregs), which make a major contribution to peripheral tolerance. FoxP3 is believed to perform a regulatory role in all the vertebrate species in which it has been detected. The prevailing view is that FoxP3 is absent in birds and that avian...

The serum or plasma biochemical profile is essential in the diagnosis and monitoring of systemic disease in veterinary medicine, but current reference intervals typically take no account of breed-specific differences. Breed-specific hematological phenotypes have been documented in the domestic dog, but little has been published on serum biochemical...

Anonymized biochemistry data. (XLSX)

A comparison of the results of principal component analysis with pairwise comparative analysis. Breeds with a distinctive phenotype identified by principal component analysis are designated in blue, and breeds identified by pairwise comparisons with the mixed breed group are indicated in red. Complementarity was generally observed between the metho...

Detailed samples inclusion and exclusion criteria, specimen collection, analysis, and quality control and statistical methods. (DOCX)

Histograms of the serum biochemical data for the Labrador Retriever (n = 327). (TIF)

Histograms of the serum biochemical data for the German Shepherd Dog (n = 160). (TIF)

Tables A-R, descriptive statistics for all serum biochemical data. Table S, p-values for the effects of age, sex and neutering status on serum biochemical profile. Table T, eigenvalues for the principal component analysis. Table U, pairwise comparison results between the pure breed and mixed breed dogs. Tables V-Z, tentative breed-specific referenc...

Effects of age, sex and neutering status on biochemical analytes for the Labrador Retriever (n = 327). The adjusted mean values ± 1 standard error bars for each of the 18 biochemical analytes are represented on the respective y axes, showing age in years on the x axes. Intact male and female dogs are represented by the solid black and red lines; ne...

Histograms of the serum biochemical data for the Boxer (n = 146). (TIF)

Histograms of the serum biochemical data for the Golden Retriever (n = 121). (TIF)

Histograms of the serum biochemical data for the Cavalier King Charles Spaniel (n = 174). (TIF)

Table S1. Complete CBC and serum biochemistry results comparing Group 1 and Group 2.

Background: Cholecystocentesis can be part of the diagnostic workup of hepatobiliary disease in small animals, but literature on cytological evaluation of bile is scant. Objectives: To determine the diagnostic utility of cytological assessment of bile aspirates. Animals: Fifty-six and 78 client-owned dogs and cats, respectively, with bile coll...