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1.
J Vet Diagn Invest ; : 10406387241267899, 2024 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-39152702

RESUMEN

The rostral cranial fossa (RCF) consists of the sphenoid and ethmoid bones, which accommodate the olfactory bulbs and nerves along the recesses of the cribriform plate. Neoplasms located in the vicinities of the RCF can compress and/or invade the cribriform plate. Here we describe the clinical and pathologic findings of neoplasms involving the cribriform plate in 32 dogs and 17 cats autopsied over a 13-y period. The average ages of affected dogs and cats were 9.2 y and 9.7 y, respectively. No sex or breed predisposition was evident in dogs, but 13 of 18 cats were spayed females and 14 of 18 were domestic shorthair cats. The main clinical signs were seizures (10 cases) and epistaxis (5 cases) in dogs, and red-to-brown nasal discharge (5 cases) and seizures (4 cases) in cats. In dogs, the 22 sinonasal neoplasms included adenocarcinoma (14 cases), transitional carcinoma (4), squamous cell carcinoma (2), lymphoma (1), and histiocytic sarcoma (1); the 10 intracranial neoplasms consisted of high-grade gliomas (3 cases), psammomatous meningiomas (2), histiocytic sarcomas (2), olfactory neuroblastomas (2), and a meningeal granular cell tumor (1). In cats, the 14 sinonasal neoplasms included lymphoma (8 cases), adenocarcinoma (4), adenosquamous carcinoma (1), and squamous cell carcinoma (1); the 3 intracranial neoplasms consisted of oligodendroglioma (1), transitional meningioma (1), and olfactory neuroblastoma (1).

2.
Mov Disord ; 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39177409

RESUMEN

BACKGROUND: Neuroaxonal dystrophy (NAD) is a group of inherited neurodegenerative disorders characterized primarily by the presence of spheroids (swollen axons) throughout the central nervous system. In humans, NAD is heterogeneous, both clinically and genetically. NAD has also been described to naturally occur in large animal models, such as dogs. A newly recognized disorder in Miniature American Shepherd dogs (MAS), consisting of a slowly progressive neurodegenerative syndrome, was diagnosed as NAD via histopathology. OBJECTIVES: To describe the clinical and pathological phenotype together with the identification of the underlying genetic cause. METHODS: Clinical and postmortem evaluations, together with a genome-wide association study and autozygosity mapping approach, followed by whole-genome sequencing. RESULTS: Affected dogs were typically young adults and displayed an abnormal gait characterized by pelvic limb weakness and ataxia. The underlying genetic cause was identified as a 1-bp (base pair) deletion in RNF170 encoding ring finger protein 170, which perfectly segregates in an autosomal recessive pattern. This deletion is predicted to create a frameshift (XM_038559916.1:c.367delG) and early truncation of the RNF170 protein (XP_038415844.1:(p.Ala123Glnfs*11)). The age of this canine RNF170 variant was estimated at ~30 years, before the reproductive isolation of the MAS breed. CONCLUSIONS: RNF170 variants were previously identified in human patients with autosomal recessive spastic paraplegia-85 (SPG85); this clinical phenotype shows similarities to the dogs described herein. We therefore propose that this novel MAS NAD could serve as an excellent large animal model for equivalent human diseases, particularly since affected dogs demonstrate a relatively long lifespan, which represents an opportunity for therapeutic trials. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

3.
JFMS Open Rep ; 10(2): 20551169241241208, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39070185

RESUMEN

Case series summary: Two cats, aged 13.5 and 14 years, presented with duodenal masses ultimately diagnosed as Brunner's gland (BG) adenomas. In the first cat, the lesion was a firm, pale tan, proximal duodenal polyp adjacent to the major duodenal papilla that was composed histologically of a well demarcated, expansile mass of well-differentiated BGs separated by fibrovascular septa and few adipocytes. This patient was euthanized for otitis-related vestibular signs, and the clinical significance of the duodenal polyp is unknown. The second cat presented with a 6-month history of vomiting. This cat had a mural duodenal mass in the region of the major duodenal papilla of approximately 2 cm, which was histologically composed of a dense population of variably ectatic BGs expanding the submucosa and lamina propria. This patient's mass was non-resectable, but the vomiting resolved after palliative gastroenterostomy loop surgery to allow ingesta to flow past the mass. The patient survived 35 months after the procedure. Relevance and novel information: BG adenoma is a rare, typically benign tumor in humans with non-specific clinical manifestations and no clear etiopathogenesis. This lesion, and the related condition BG hyperplasia, has been documented rarely in animals (one dog, two horses, and in mice and rats). This is the first description of the lesion in the cat. The comparative pathology, differential diagnoses and possible significance of these lesions are discussed.

4.
J Am Vet Med Assoc ; 262(3): 1-4, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38183769

RESUMEN

OBJECTIVE: To describe the clinical presentation, novel surgical approach, and outcome of a dog diagnosed with chondro-osseous respiratory epithelial adenomatoid hamartoma (COREAH). ANIMAL: 5-year-old castrated male Yorkshire Terrier. CLINICAL PRESENTATION, PROGRESSION, AND PROCEDURES: The dog was presented with chronic upper respiratory noise, congestion, facial swelling, ocular discharge, and an abscess on the nasal bridge. Two CT scans were performed 4 months apart. The CT scans yielded similar results: cyst-like nasal masses with severely destructive bilateral rhinitis with extensive polyostotic bony lysis. A dorsal rhinotomy with a turbinectomy and debridement of the nasal cavity were performed. A poorly defined but extensive lesion was found occupying the entirety of the left frontal sinus as well as the nasal cavity. TREATMENT AND OUTCOME: Histopathology revealed a mass consistent with COREAH. The dog recovered well from surgery, except for self-limiting subcutaneous emphysema, and 3 weeks postoperatively was reportedly doing well, with mild nasal discharge. Stridor, nasal discharge, and sneezing episodes were reported postoperatively; however, these were improved. At 18 months postoperatively, the dog died from uncontrolled seizures while hospitalized for suspected acute hemorrhagic diarrhea syndrome at a different hospital. CLINICAL RELEVANCE: COREAH should be considered a potential cause of destructive bilateral rhinitis and bony lysis in dogs. Dorsal rhinotomy can be a surgical treatment for dogs with possible COREAH with acceptable outcome, though complete remission of clinical signs may not be achieved. This is the first clinical description of COREAH in a dog.


Asunto(s)
Adenoma , Enfermedades de los Perros , Hamartoma , Neoplasias Nasales , Rinitis , Perros , Masculino , Animales , Nariz/patología , Cavidad Nasal/patología , Rinitis/veterinaria , Neoplasias Nasales/veterinaria , Adenoma/veterinaria , Hamartoma/diagnóstico , Hamartoma/cirugía , Hamartoma/veterinaria , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/cirugía , Enfermedades de los Perros/patología
5.
J Vet Diagn Invest ; 36(2): 153-168, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38234003

RESUMEN

The diagnosis of primary and secondary CNS neoplasms of dogs and cats relies on histologic examination of autopsy or biopsy samples. In addition, many neoplasms must be further characterized by immunohistochemistry (IHC) for a more refined diagnosis in specific cases. Given the many investigations assessing the diagnostic and prognostic IHC profile of CNS neoplasms in the veterinary literature, it may be difficult for the diagnostic pathologist or pathology trainee to narrow the list of reliable diagnostic IHCs when facing a challenging case. Here we compile a comprehensive list of the most diagnostically relevant immunomarkers that should be utilized for the diagnostic support or confirmation of the most common primary and secondary CNS neoplasms of dogs and cats.


Asunto(s)
Enfermedades de los Gatos , Neoplasias del Sistema Nervioso Central , Enfermedades de los Perros , Gatos , Perros , Animales , Enfermedades de los Gatos/diagnóstico , Enfermedades de los Gatos/patología , Inmunohistoquímica , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/patología , Neoplasias del Sistema Nervioso Central/diagnóstico , Neoplasias del Sistema Nervioso Central/veterinaria , Neoplasias del Sistema Nervioso Central/patología , Pronóstico
6.
Vet Pathol ; 61(2): 171-178, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37577961

RESUMEN

Leptomeningeal gliomatosis (LG) is characterized by extensive dissemination of neoplastic glial cells in the subarachnoid space either without an intraparenchymal glioma (primary LG or PLG) or secondary to an intraparenchymal glioma (secondary LG or SLG). Given the low frequency of LG in human and veterinary medicine, specific diagnostic criteria are lacking. Here, we describe 14 cases of canine LG that were retrospectively identified from 6 academic institutions. The mean age of affected dogs was 7.3 years and over 90% of patients were brachycephalic. Clinical signs were variable and progressive. Relevant magnetic resonance image findings in 7/14 dogs included meningeal enhancement of affected areas and/or intraparenchymal masses. All affected dogs were euthanized because of the poor prognosis. Gross changes were reported in 12/14 cases and consisted mainly of gelatinous leptomeningeal thickening in the brain (6/12 cases) or spinal cord (2/12 cases) and 1 or multiple, gelatinous, gray to red intraparenchymal masses in the brain (6/12 cases). Histologically, all leptomeningeal neoplasms and intraparenchymal gliomas were morphologically consistent with oligodendrogliomas. Widespread nuclear immunolabeling for OLIG2 was observed in all neoplasms. The absence of an intraparenchymal glioma was consistent with PLG in 3 cases. The remaining 11 cases were diagnosed as SLG.


Asunto(s)
Enfermedades de los Perros , Glioma , Neoplasias Meníngeas , Humanos , Perros , Animales , Estudios Retrospectivos , Glioma/diagnóstico , Glioma/veterinaria , Neoplasias Meníngeas/veterinaria , Neoplasias Meníngeas/diagnóstico , Médula Espinal/diagnóstico por imagen , Médula Espinal/patología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Imagen por Resonancia Magnética/veterinaria , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/patología
7.
J Vet Intern Med ; 38(1): 258-267, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37916855

RESUMEN

BACKGROUND: Fibrocartilaginous embolic myelopathy (FCE) is a well-documented condition in dogs although rarely reported in chondrodystrophic breeds. Genetic associations have not been defined. OBJECTIVES: Define the association of the chondrodystrophy-associated FGF4L2 retrogene with histopathologically confirmed cases of FCE. ANIMALS: Ninety-eight dogs with a histopathologic diagnosis of FCE. METHODS: Retrospective multicenter study. Dogs were genotyped for the FGF4L2 and FGF4L1 retrogenes using DNA extracted from formalin-fixed, paraffin-embedded tissue. Associations between breed, FCE and retrogene status were investigated with reference to a hospital population and known breed and general population allele frequencies. RESULTS: FGF4L2 genotype was defined in 89 FCE cases. Fibrocartilaginous embolic myelopathy was present in 22 dogs from FGF4L2-segregating breeds with allele frequencies of ≥5%; however, all dogs were wild type. Two Labrador retrievers with FCE carried FGF4L2 alleles. Frequency of the FGF4L2 allele was significantly (P < .001) and negatively associated with FCE relative to predicted hospital-population dogs. FCE was overrepresented in Boxer, Great Dane, Yorkshire Terrier, Bernese Mountain Dog, Miniature Schnauzer, Rottweiler, and Shetland Sheepdog breeds. CONCLUSIONS AND CLINICAL IMPORTANCE: Study data based on genotypically and histopathologically defined cases support the historical observation that FCE is uncommon in chondrodystrophic dog breeds. FGF4 plays an important role in angiogenesis and vascular integrity; anatomical studies comparing chondrodystrophic and non-chondrodystrophic dogs might provide insight into the pathogenesis of FCE.


Asunto(s)
Enfermedades de los Cartílagos , Enfermedades de los Perros , Embolia , Enfermedades de la Médula Espinal , Animales , Perros , Enfermedades de los Cartílagos/genética , Enfermedades de los Cartílagos/veterinaria , Enfermedades de los Cartílagos/complicaciones , Enfermedades de los Perros/diagnóstico , Genotipo , Enfermedades de la Médula Espinal/genética , Enfermedades de la Médula Espinal/veterinaria
8.
J Clin Psychol ; 80(4): 855-870, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37561065

RESUMEN

OBJECTIVE: Cognitive-behavioral therapy (CBT), which includes a decided emphasis on exposure and response/ritual prevention (ERP) and between-session practice of treatment principles, has consistently demonstrated efficacy for the treatment of obsessive-compulsive disorder (OCD) and is a gold standard, recommended first-line treatment. CBT with ERP has been successfully adapted to fit the needs of autistic individuals with OCD. The present article provides a brief overview of CBT for OCD and outlines special considerations and adaptations needed when working with patients with OCD and comorbid autism, with an emphasis on the importance of between-session homework. METHOD: A case vignette is presented. RESULTS: This case study illustrates the role of homework in the exposure-based treatment of an adult autistic individual with comorbid OCD. CONCLUSION: Implications of this case vignette are discussed, and recommendations are offered for clinicians working with autistic individuals with OCD, especially in regard to bolstering completion of between-session ERP homework.


Asunto(s)
Trastorno Autístico , Terapia Cognitivo-Conductual , Trastorno Obsesivo Compulsivo , Adulto , Humanos , Trastorno Autístico/terapia , Resultado del Tratamiento , Trastorno Obsesivo Compulsivo/terapia
9.
Annu Rev Clin Psychol ; 20(1): 355-380, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38100637

RESUMEN

Obsessive-compulsive disorder (OCD) in children and adolescents is a neurobehavioral condition that can lead to functional impairment in multiple domains and decreased quality of life. We review the clinical presentation, diagnostic considerations, and common comorbidities of pediatric OCD. An overview of the biological and psychological models of OCD is provided along with a discussion of developmental considerations in youth. We also describe evidence-based treatments for OCD in childhood and adolescence, including cognitive behavioral therapy (CBT) with exposure and response prevention (ERP) and pharmacotherapy. Finally, research evaluating the delivery of CBT in different formats and modalities is discussed, and we conclude with suggestions for future research directions.


Asunto(s)
Trastorno Obsesivo Compulsivo , Humanos , Trastorno Obsesivo Compulsivo/terapia , Trastorno Obsesivo Compulsivo/fisiopatología , Niño , Adolescente , Terapia Cognitivo-Conductual/métodos
11.
J Vet Diagn Invest ; 35(6): 800-805, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37608783

RESUMEN

Distinct patterns of local infiltration are a common feature of canine oligodendroglioma and astrocytoma, and typically involve the surrounding neuroparenchyma, ventricles, or leptomeninges. Infiltration of adjacent extraneural sites is rare and has not been well documented in veterinary medicine. Here we describe 6 canine gliomas with cribriform plate involvement (compression or infiltration) and caudal nasal invasion confirmed by neuroimaging, autopsy, and/or histology. All affected dogs were adults (9-12-y-old), and 3 were brachycephalic. Clinical signs were associated with the brain tumor, with no respiratory signs reported. Magnetic resonance imaging in 2 patients revealed a rostral intraparenchymal telencephalic mass with extension into the cribriform plate. All dogs were euthanized. Gross changes consisted of poorly demarcated, white or pale-yellow, soft, and, in oligodendrogliomas, gelatinous, intraparenchymal masses that expanded the rostral portions of the telencephalon and adhered firmly to the ethmoid bone and cribriform plate. Gliomas were classified as high-grade oligodendrogliomas (4 cases) and high-grade astrocytomas (2 cases) based on histology and immunohistochemistry for OLIG2 and GFAP. In all cases, there was evidence of cribriform plate invasion and, in one case, additional invasion of the caudal nasal cavity.


Asunto(s)
Astrocitoma , Neoplasias Encefálicas , Glioma , Oligodendroglioma , Humanos , Perros , Animales , Oligodendroglioma/patología , Oligodendroglioma/veterinaria , Hueso Etmoides/patología , Glioma/diagnóstico por imagen , Glioma/veterinaria , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/veterinaria , Astrocitoma/patología , Astrocitoma/veterinaria
12.
JFMS Open Rep ; 9(1): 20551169231165270, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37197686

RESUMEN

Case summary: A 15-year-old male castrated domestic shorthair cat originally presented to its primary care veterinarian with a chief complaint of a multi-month history of decreased appetite, weight loss and mild weight-bearing lameness. On physical examination, over the right scapula there was mild-to-moderate muscle wasting and a palpable firm, bony mass measuring approximately 3.5 cm × 3 cm. A complete blood count, chemistry panel, urinalysis, urine culture and baseline thyroxine were clinically unremarkable. Further diagnostics included CT, which revealed a large, expansile, irregularly mineralized mass centered over the caudoventral scapula at the site of attachment of the infraspinatus muscle. Following wide surgical excision by means of complete scapulectomy the patient regained function of the limb and has been free of disease since. The clinical institution's pathology service examined the resected scapula with associated mass and diagnosed an intraosseous lipoma. Relevance and novel information: Intraosseous lipoma is a rare form of bone neoplasia that has only been reported once in the small animal veterinary literature. Histopathology, clinical signs and radiographic changes were consistent with what is described in human literature. It is hypothesized that these tumors occur because of invasively growing adipose tissue within the medullary canal following trauma. Considering the rarity of primary bone tumors in cats, intraosseous lipomas should be considered as a differential diagnosis in future cases with similar signs and history.

13.
JFMS Open Rep ; 8(2): 20551169221117516, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36003069

RESUMEN

Case summary: An adult male neutered Russian Blue cat presented for a right-sided nasal mass with bilateral retropharyngeal and right mandibular lymphadenomegaly. Medial retropharyngeal lymph node excision with nasal mass biopsy revealed eosinophilic sclerosing lymphadenitis and eosinophilic and lymphoplasmacytic rhinitis, respectively. Bacterial culture of the lymph node grew Pseudomonas aeruginosa, and treatment with pradofloxacin was started. Despite initial improvement, clinical signs recurred after 9 months, and fine-needle aspirates of the right mandibular and left medial retropharyngeal lymph nodes showed eosinophilic and mastocytic infiltration. Bacterial culture of the left medial retropharyngeal lymph node grew P aeruginosa, and treatment with anti-inflammatory doses of prednisolone and, later, marbofloxacin was instituted. Relevance and novel information: This report describes a case of feline eosinophilic sclerosing lymphadenitis diagnosed outside of the abdominal cavity and is the first case reported to be associated with P aeruginosa. Feline eosinophilic sclerosing lymphadenitis should be considered as a differential for lymphadenopathy occurring in areas other than the abdominal cavity. Feline eosinophilic sclerosing lymphadenitis may develop in cats due to a species-specific inflammatory response to chronic bacterial and fungal infections.

14.
Vet Radiol Ultrasound ; 63(2): 176-184, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34881469

RESUMEN

Intracranial extra-axial histiocytic sarcoma shares common MRI features with meningioma. As histiocytic sarcoma carries a generally worse prognosis than meningioma, the ability to differentiate between these two neoplasms is of clinical value. The aim of this retrospective diagnostic accuracy and observer agreement study was to evaluate the accuracy and reliability of high-field MRI to differentiate between these two tumors, using standard pulse sequences and published MRI features. A total of 51 dogs were included (26 meningiomas and 25 histiocytic sarcomas). Magnetic resonance imaging examinations were independently assessed by three experienced board-certified radiologists, evaluating 18 imaging features. They were asked to assign each case to one of three categories (meningioma, histiocytic sarcoma, and undetermined). Agreement for the MRI diagnosis across all three reviewers was moderate (κ 0.54) while paired interobserver agreement ranged from moderate to substantial (κ 0.58-0.74) with percent agreement ranging between 86.1% and 87.7%. Overall, the probability of correctly diagnosing meningioma in a dog with this tumor ranged between 79.2% and 94.4%, and the probability of correctly diagnosing histiocytic sarcoma in a dog with this tumor ranged between 76.0% and 92.3%. The overall probability to diagnose the correct tumor, irrespective of type, ranged between 79.2% and 89.7%. Histiocytic sarcomas tended to have more extensive edema and more often had combined perilesional and distant meningeal enhancement affecting both pachy- and leptomeninges, while for meningiomas, meningeal enhancement tended to more commonly be perilesional and pachymeningeal. Imaging features that seemed more useful to make a correct diagnosis included "location/type of meningeal enhancement," "osseous changes in the adjacent neurocranium," "cystic changes," and "herniation severity."


Asunto(s)
Enfermedades de los Perros , Sarcoma Histiocítico , Neoplasias Meníngeas , Meningioma , Animales , Enfermedades de los Perros/patología , Perros , Sarcoma Histiocítico/diagnóstico por imagen , Sarcoma Histiocítico/veterinaria , Imagen por Resonancia Magnética/métodos , Imagen por Resonancia Magnética/veterinaria , Neoplasias Meníngeas/diagnóstico por imagen , Neoplasias Meníngeas/veterinaria , Meningioma/diagnóstico por imagen , Meningioma/veterinaria , Variaciones Dependientes del Observador , Reproducibilidad de los Resultados , Estudios Retrospectivos
15.
J Immunol ; 207(1): 44-54, 2021 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-34162727

RESUMEN

Multiple sclerosis (MS) is an idiopathic demyelinating disease in which meningeal inflammation correlates with accelerated disease progression. The study of meningeal inflammation in MS has been limited because of constrained access to MS brain/spinal cord specimens and the lack of experimental models recapitulating progressive MS. Unlike induced models, a spontaneously occurring model would offer a unique opportunity to understand MS immunopathogenesis and provide a compelling framework for translational research. We propose granulomatous meningoencephalomyelitis (GME) as a natural model to study neuropathological aspects of MS. GME is an idiopathic, progressive neuroinflammatory disease of young dogs with a female bias. In the GME cases examined in this study, the meninges displayed focal and disseminated leptomeningeal enhancement on magnetic resonance imaging, which correlated with heavy leptomeningeal lymphocytic infiltration. These leptomeningeal infiltrates resembled tertiary lymphoid organs containing large B cell clusters that included few proliferating Ki67+ cells, plasma cells, follicular dendritic/reticular cells, and germinal center B cell-like cells. These B cell collections were confined in a specialized network of collagen fibers associated with the expression of the lympho-organogenic chemokines CXCL13 and CCL21. Although neuroparenchymal perivascular infiltrates contained B cells, they lacked the immune signature of aggregates in the meningeal compartment. Finally, meningeal B cell accumulation correlated significantly with cortical demyelination reflecting neuropathological similarities to MS. Hence, during chronic neuroinflammation, the meningeal microenvironment sustains B cell accumulation that is accompanied by underlying neuroparenchymal injury, indicating GME as a novel, naturally occurring model to study compartmentalized neuroinflammation and the associated pathology thought to contribute to progressive MS.


Asunto(s)
Linfocitos B/inmunología , Modelos Animales de Enfermedad , Meninges/inmunología , Esclerosis Múltiple Crónica Progresiva/inmunología , Animales , Linfocitos B/patología , Perros , Meninges/patología , Esclerosis Múltiple Crónica Progresiva/patología
16.
Brain ; 144(6): 1670-1683, 2021 07 28.
Artículo en Inglés | MEDLINE | ID: mdl-33723591

RESUMEN

The concerted actions of the CNS and the immune system are essential to coordinating the outcome of neuroinflammatory responses. Yet, the precise mechanisms involved in this crosstalk and their contribution to the pathophysiology of neuroinflammatory diseases largely elude us. Here, we show that the CNS-endogenous hedgehog pathway, a signal triggered as part of the host response during the inflammatory phase of multiple sclerosis and experimental autoimmune encephalomyelitis, attenuates the pathogenicity of human and mouse effector CD4 T cells by regulating their production of inflammatory cytokines. Using a murine genetic model, in which the hedgehog signalling is compromised in CD4 T cells, we show that the hedgehog pathway acts on CD4 T cells to suppress the pathogenic hallmarks of autoimmune neuroinflammation, including demyelination and axonal damage, and thus mitigates the development of experimental autoimmune encephalomyelitis. Impairment of hedgehog signalling in CD4 T cells exacerbates brain-brainstem-cerebellum inflammation and leads to the development of atypical disease. Moreover, we present evidence that hedgehog signalling regulates the pathogenic profile of CD4 T cells by limiting their production of the inflammatory cytokines granulocyte-macrophage colony-stimulating factor and interferon-γ and by antagonizing their inflammatory program at the transcriptome level. Likewise, hedgehog signalling attenuates the inflammatory phenotype of human CD4 memory T cells. From a therapeutic point of view, our study underlines the potential of harnessing the hedgehog pathway to counteract ongoing excessive CNS inflammation, as systemic administration of a hedgehog agonist after disease onset effectively halts disease progression and significantly reduces neuroinflammation and the underlying neuropathology. We thus unveil a previously unrecognized role for the hedgehog pathway in regulating pathogenic inflammation within the CNS and propose to exploit its ability to modulate this neuroimmune network as a strategy to limit the progression of ongoing neuroinflammation.


Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Encefalomielitis Autoinmune Experimental/inmunología , Proteínas Hedgehog/inmunología , Inflamación/inmunología , Animales , Encéfalo/inmunología , Encéfalo/patología , Linfocitos T CD4-Positivos/patología , Encefalomielitis Autoinmune Experimental/metabolismo , Encefalomielitis Autoinmune Experimental/patología , Proteínas Hedgehog/metabolismo , Humanos , Inflamación/metabolismo , Ratones , Médula Espinal/inmunología , Médula Espinal/patología
17.
Vet Comp Oncol ; 19(3): 578-586, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33774909

RESUMEN

Canine gastrointestinal sarcomas, a group of tumours that includes leiomyosarcomas (LMSAs), gastrointestinal stromal tumours (GISTs) and other rarer sarcomas, comprise about 10-30% of all gastrointestinal tumours. This study aims to characterize the histologic characteristics and clinical behaviour in order to identify prognostic factors predictive of outcome. A single institution database search for surgically treated gastrointestinal sarcomas yielded 47 cases with adequate tissue remaining for histologic analysis and 42 cases available for analysis of clinical outcome. Tumours were then prospectively evaluated for mitotic count, necrosis, haemorrhage and inflammation, as well as categorized via immunohistochemical (IHC) staining for smooth muscle actin, c-KIT and DOG-1. IHC analysis defined 32 tumours as GISTs, 14 as LMSAs and one as a sarcoma not otherwise specified. For both GISTs and LMSAs, the overall median survival time (MST) is 1024 days (range 31-1456), which did not differ statistically between tumour types (p = .92). The overall metastatic rate of GISTs in this study was 32.1% (n = 9) which was not significantly different to that of LMSAs at 15.3% (n = 2, p = .45). In multivariate analysis, mitotic count under 9 in GIST patients and complete surgical excision in all tumour types correlated with improved MST. For patients with GISTs, the intensity of c-KIT staining also correlated positively with survival, with an MST of 250 days in cases with weak staining and an MST of 1418 days in cases with moderate or strong c-KIT staining (p = .005).


Asunto(s)
Enfermedades de los Perros , Tumores del Estroma Gastrointestinal , Leiomiosarcoma , Sarcoma , Animales , Enfermedades de los Perros/diagnóstico , Perros , Tumores del Estroma Gastrointestinal/diagnóstico , Tumores del Estroma Gastrointestinal/veterinaria , Inmunohistoquímica , Leiomiosarcoma/diagnóstico , Leiomiosarcoma/veterinaria , Pronóstico , Sarcoma/diagnóstico , Sarcoma/veterinaria
18.
J Comp Pathol ; 180: 122-127, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33222869

RESUMEN

Mixed germ cell tumours occur rarely in veterinary species. This report describes a case of metastatic mixed germ cell tumour in a female Eurasian harvest mouse (Micromys minutus). The tumour was extensive in one ovary and the uterus, and was characterized by two distinct tumour cell populations with features typical of embryonal carcinoma (EC) and choriocarcinoma (CC). Metastases of CC to the lungs and liver were observed. The exact origin of the CC was unclear, but the possibility of a non-gestational CC is favoured, given the context of a mixed germ cell tumour and lack of p53 expression. EC diagnosis was confirmed by immunohistochemical labelling of CD30 and lack of immunoreactivity for c-Kit. In addition, membranous ß-catenin expression was present in the EC component, indicating an inactive Wnt/ß-catenin pathway, which is required for the maintenance of pluripotency.


Asunto(s)
Carcinoma Embrionario , Coriocarcinoma , Neoplasias de Células Germinales y Embrionarias , Enfermedades de los Roedores , Animales , Carcinoma Embrionario/veterinaria , Coriocarcinoma/veterinaria , Femenino , Antígeno Ki-1 , Ratones , Neoplasias de Células Germinales y Embrionarias/veterinaria
19.
Vector Borne Zoonotic Dis ; 20(6): 418-426, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32017860

RESUMEN

Leptospirosis is a globally important, fatal disease of humans, and over 160 species of animals are associated with more than 250 bacterial serovars in 64 species, but its ecology varies regionally and has changed over time with expansion of human development on previously agricultural and wild land. Sporadic human cases and clusters of canine leptospirosis, primarily attributable to Leptospira interrogans serogroup Pomona, have been detected in northern California. Small mesocarnivores such as raccoons and skunks frequent peridomestic space across much of the western United States and could serve as reservoirs for human and canine leptospirosis. We aimed to summarize the prevalence of infection with pathogenic leptospires in skunk and raccoon renal and urinary samples across broad geographic zones in California, and to determine whether prevalence changed during wet and dry seasons, and as functions of host species and demographic characters. Overall, 25.6% (22/86 tested) of raccoons and 28.5% (39/137 tested) of skunks were PCR-positive for Leptospira spp. in either renal tissue or urine, with leptospiral DNA in 22.0% of kidney samples and 18.8% of urine samples from raccoons and 27.8% and 14.5% of kidney and urine samples from skunks, respectively. Raccoons from the Central California and skunks from the San Francisco Bay Area had the highest overall PCR-prevalence (35.7% and 44.4%), respectively, and adults were more likely to be PCR-positive for Leptospira spp. than juveniles. There was moderate agreement between urine and renal tissue Leptospira spp. PCR with sensitivity for both host species in renal tissue of 0.86-0.97 and 0.42-0.64 in urine. Cases of human leptospirosis are thought to be underrecognized in the continental United States and possibly increasing in some states, including California. Our data document regionally high rates of infection in common mesocarnivores, which can pose a threat to humans and dogs, revealing an important periurban epidemiological cycle.


Asunto(s)
Reservorios de Enfermedades/veterinaria , Leptospira/aislamiento & purificación , Leptospirosis/veterinaria , Mephitidae/microbiología , Mapaches/microbiología , Animales , California/epidemiología , Reservorios de Enfermedades/microbiología , Femenino , Leptospirosis/epidemiología , Leptospirosis/microbiología , Masculino , Mephitidae/orina , Mapaches/orina , Factores de Riesgo , Estaciones del Año , Especificidad de la Especie
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