RESUMO
An 11-year-old captive, female Houston toad (Anaxyrus houstonensis) became lethargic and reluctant to move. This toad had been administered human chorionic gonadotropin (HCG) and luteinizing hormone-releasing hormone (LHRH) annually as part of a hormone-assisted captive propagation programme for 8 years. Due to poor prognosis, euthanasia was elected. At necropsy, the liver was moderately enlarged, diffusely dark red and had a nodular superficial appearance. Microscopically, the hepatic nodules consisted of poorly demarcated, non-encapsulated, paucicellular infiltrative neoplastic growths. These consisted of spindle cells, similar to sinusoidal endothelial cells, that formed irregular blood-filled vascular channels resembling sinusoids separated by thin bands of collagen and reticulin fibres. Neoplastic cells dissected through and replaced hepatic cords and bile ducts. Based on the cytohistomorphological features and analogy with vascular neoplasms in other vertebrates, a diagnosis of low-grade angiosarcoma was made. To the best of our knowledge, this is the first record of primary hepatic vascular neoplasia in an amphibian. It is not known if the long-term administration of HCG and LHRH had any oncogenic role in this animal. Vascular neoplasia should be included in the differential diagnosis of hepatomegaly and non-specific lethargy and health decline in amphibian species.
Assuntos
Bufonidae , Neoplasias Vasculares , Animais , Gonadotropina Coriônica , Células Endoteliais , Evolução Fatal , Feminino , Hormônio Liberador de Gonadotropina , Fígado/irrigação sanguínea , Fígado/patologia , Neoplasias Vasculares/veterináriaRESUMO
A 3-mo-old, female Boer goat was presented because of respiratory difficulties. Tachypnea and inspiratory dyspnea were noted during physical examination. Thoracic radiographs were unremarkable; however, upper airway and nasal passage radiographs revealed a soft tissue mass within the nasal passages. The patient underwent cardiorespiratory arrest and did not respond to resuscitation efforts during endoscopy. A large, pedunculated, semi-firm mass originated from the soft palate and obstructed 90% of the nasopharynx on autopsy. Histologically, the mass was composed of primitive cells that multifocally formed tubules and glomeruloid structures intermingled with areas of fusiform and blastemal cells. The neoplastic cells were positive for cytokeratin (tubular and glomeruloid cells), vimentin (fusiform population and blastemal cells), and Wilms tumor 1 protein (glomeruloid structures) on immunohistochemistry, consistent with a triphasic nephroblastoma. To our knowledge, nasopharyngeal nephroblastoma has not been reported previously in any species.
Assuntos
Doenças das Cabras/diagnóstico , Neoplasias Nasofaríngeas/veterinária , Tumor de Wilms/veterinária , Animais , Diagnóstico Diferencial , Feminino , Doenças das Cabras/classificação , Doenças das Cabras/diagnóstico por imagem , Doenças das Cabras/patologia , Cabras , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/patologia , Tumor de Wilms/diagnóstico , Tumor de Wilms/diagnóstico por imagem , Tumor de Wilms/patologiaRESUMO
BACKGROUND: Functional MRI (fMRI) task-related analyses rely on an estimate of the brain's hemodynamic response function (HRF) to model the brain's response to events. Although changes in the HRF have been found after acute alcohol administration, the effects of heavy chronic alcohol consumption on the HRF have not been explored, and the potential benefits or pitfalls of estimating each individual's HRF on fMRI analyses of chronic alcohol use disorder (AUD) are not known. METHODS: Participants with AUD and controls (CTL) received structural, functional, and vascular scans. During fMRI, participants were cued to tap their fingers, and averaged responses were extracted from the motor cortex. Curve fitting on these HRFs modeled them as a difference between 2 gamma distributions, and the temporal occurrence of the main peak and undershoot of the HRF was computed from the mean of the first and second gamma distributions, respectively. RESULTS: ANOVA and regression analyses found that the timing of the HRF undershoot increased significantly as a function of total lifetime drinking. Although gray matter volume in the motor cortex decreased with lifetime drinking, this was not sufficient to explain undershoot timing shifts, and vascular factors measured in the motor cortex did not differ among groups. Comparison of random-effects analyses using custom-fitted and canonical HRFs for CTL and AUD groups showed better results throughout the brain for custom-fitted versus canonical HRFs for CTL subjects. For AUD subjects, the same was true except for the basal ganglia. CONCLUSIONS: These findings suggest that excessive alcohol consumption is associated with changes in the HRF undershoot. HRF changes could provide a possible biomarker for the effects of lifetime drinking on brain function. Changes in HRF topography affect fMRI activation measures, and subject-specific HRFs generally improve fMRI activation results.
Assuntos
Alcoolismo/fisiopatologia , Encéfalo/irrigação sanguínea , Hemodinâmica/efeitos dos fármacos , Adulto , Encéfalo/patologia , Encéfalo/fisiopatologia , Etanol/administração & dosagem , Feminino , Substância Cinzenta/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Córtex Motor/irrigação sanguínea , Córtex Motor/patologia , Córtex Motor/fisiopatologia , FumarAssuntos
Síndromes de Imunodeficiência/diagnóstico , Linfócitos/fisiologia , Proteínas de Neoplasias/genética , Deleção de Sequência/genética , Molécula 1 de Interação Estromal/genética , Células Cultivadas , Pré-Escolar , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Eczema , Humanos , Ictiose , Síndromes de Imunodeficiência/genética , Síndromes de Imunodeficiência/terapia , Lactente , Infecções , Masculino , Linhagem , FenótipoRESUMO
Stimulator of interferon genes (STING) is an endoplasmic reticulum (ER) signaling adaptor that is essential for the type I interferon response to DNA pathogens. Aberrant activation of STING is linked to the pathology of autoimmune and autoinflammatory diseases. The rate-limiting step for the activation of STING is its translocation from the ER to the ER-Golgi intermediate compartment. Here, we found that deficiency in the Ca2+ sensor stromal interaction molecule 1 (STIM1) caused spontaneous activation of STING and enhanced expression of type I interferons under resting conditions in mice and a patient with combined immunodeficiency. Mechanistically, STIM1 associated with STING to retain it in the ER membrane, and coexpression of full-length STIM1 or a STING-interacting fragment of STIM1 suppressed the function of dominant STING mutants that cause autoinflammatory diseases. Furthermore, deficiency in STIM1 strongly enhanced the expression of type I interferons after viral infection and prevented the lethality of infection with a DNA virus in vivo. This work delineates a STIM1-STING circuit that maintains the resting state of the STING pathway.