Assuntos
Leucemia Mielomonocítica Crônica/complicações , Xantogranuloma Necrobiótico/complicações , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Leucemia Mielomonocítica Crônica/patologia , Pessoa de Meia-Idade , Xantogranuloma Necrobiótico/patologia , Xantogranuloma Necrobiótico/cirurgiaRESUMO
Graft-versus-host disease-associated angiomatosis (GVHD-AA) is an uncommon manifestation of chronic GVHD consisting of friable vascular proliferations. Using fluorescence in situ hybridization, we demonstrate the presence of donor-derived endothelial cells within areas of GVHD-AA. This is the first documented occurrence of a benign neoplastic growth in relationship to a form of chronic GVHD.
Assuntos
Angiomatose/etiologia , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Escleroderma Sistêmico/etiologia , Quimeras de Transplante , Quimera , Doença Crônica , Células Endoteliais , Feminino , Humanos , Cromossomos Sexuais , Transplante HomólogoRESUMO
While Epstein-Barr virus (EBV) was initially discovered and characterized as an oncogenic virus in B cell neoplasms, it also plays a complex and multifaceted role in T/NK cell lymphomas. In B cell lymphomas, EBV-encoded proteins have been shown to directly promote immortalization and proliferation through stimulation of the NF-κB pathway and increased expression of anti-apoptotic genes. In the context of mature T/NK lymphomas (MTNKL), with the possible exception on extranodal NK/T cell lymphoma (ENKTL), the virus likely plays a more diverse and nuanced role. EBV has been shown to shape the tumor microenvironment by promoting Th2-skewed T cell responses and by increasing the expression of the immune checkpoint ligand PD-L1. The type of cell infected, the amount of plasma EBV DNA, and the degree of viral lytic replication have all been proposed to have prognostic value in T/NK cell lymphomas. Latency patterns of EBV infection have been defined using EBV-infected B cell models and have not been definitively established in T/NK cell lymphomas. Identifying the expression profile of EBV lytic proteins could allow for individualized therapy with the use of antiviral medications. More work needs to be done to determine whether EBV-associated MTNKL have distinct biological and clinical features, which can be leveraged for risk stratification, disease monitoring, and therapeutic purposes.
Assuntos
Infecções por Vírus Epstein-Barr/virologia , Células Matadoras Naturais/virologia , Linfoma de Células T/virologia , Humanos , PrognósticoAssuntos
Linfócitos B/metabolismo , Sequência de Bases , Regulação Neoplásica da Expressão Gênica , Linfoma não Hodgkin/genética , Fator de Transcrição PAX7/genética , Deleção de Sequência , Adulto , Idoso de 80 Anos ou mais , Linfócitos B/patologia , Cromossomos Humanos Par 1 , Humanos , Linfoma não Hodgkin/patologia , Pessoa de Meia-Idade , Dados de Sequência Molecular , Monossomia , Taxa de Mutação , Estadiamento de Neoplasias , Fator de Transcrição PAX7/deficiência , Análise de Regressão , Estudos RetrospectivosAssuntos
Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/fisiologia , Doença dos Neurônios Motores/genética , Proteinopatias TDP-43/genética , Proteinopatias TDP-43/patologia , Idoso de 80 Anos ou mais , Doença de Alzheimer/patologia , Autopsia , Encéfalo/patologia , DNA/genética , Éxons/genética , Evolução Fatal , Humanos , Masculino , Mutação/fisiologia , Mutação de Sentido Incorreto/genética , Medula Espinal/patologiaRESUMO
Developing neuronal populations undergo significant attrition by natural cell death. Dopaminergic neurons in the substantia nigra pars compacta undergo apoptosis during synaptogenesis. Following this time window, destruction of the anatomic target of dopaminergic neurons results in dopaminergic cell death but the morphology is no longer apoptotic. We describe ultrastructural changes that appear unique to dying embryonic dopaminergic neurons. In primary cultures of mesencephalon, death of dopaminergic neurons is triggered by activation of glutamate receptors sensitive to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and differs ultrastructurally from both neuronal apoptosis or typical excitotoxicity. AMPA causes morphological changes selectively in dopaminergic neurons, without affecting other neurons in the same culture dishes. Two hours after the onset of treatment swelling of Golgi complexes is apparent. At 3 h, dopaminergic neurons display loss of membrane asymmetry (coinciding with commitment to die), as well as nuclear membrane invagination, irregular aggregation of chromatin, and mitochondrial swelling. Nuclear changes continue to worsen until loss of cytoplasmic structures and cell death begins to occur after 12 h. These changes are different from those described in neurons undergoing either apoptosis or excitotoxic death, but are similar to ultrastructural changes observed in spontaneous death of dopaminergic neurons in the natural mutant weaver mouse.