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1.
Clin Transplant ; 34(6): e13852, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32167191

RESUMO

INTRODUCTION: One-year post-transplant survival is a significant quality measure for solid organ transplant programs in the United States. It is not known whether the use of this metric is associated with changes in life-sustaining clinical practices that would delay mortality for solid organ recipients until just beyond the one-year time point. METHODS: We compared trends in mortality in the time period immediately preceding the one-year post-transplant mark compared to the period immediately after using second-order Cox proportional hazard regression models. RESULTS: Among recipients of heart, liver, and lung transplantation, mortality did not decrease significantly in the period immediately before day 365 or increase in the 14 days thereafter. There was an increased adjusted hazard of mortality in the 30 days following day 365 among lung transplant recipients (HR 1.33, 95% CI 1.03-1.72, P = .03) with a 0.76% absolute mortality rate (94 deaths) in month 12 following lung transplantation and a 1.14% absolute mortality rate in month 13 (113 deaths). CONCLUSION: Although we did not find evidence that life-sustaining treatment is routinely continued until just beyond the one-year mark in heart and liver transplantation recipients, there was an unexpected increased risk of mortality in the 30 days following day 365 among lung transplant recipients.


Assuntos
Transplante de Coração , Transplante de Pulmão , Transplante de Órgãos , Humanos , Fígado , Sistema de Registros , Transplantados , Estados Unidos/epidemiologia
2.
J Cutan Pathol ; 46(12): 954-959, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31283031

RESUMO

The epithelioid blue nevus (EBN) is a variant of the blue nevus characterized by heavily pigmented epithelioid melanocytes and lightly or nonpigmented spindle cells. It may be associated with Carney complex, a multiple neoplasia syndrome. Congenital cases of EBN not associated with Carney complex are rarely reported. We herein describe an infant who presented with multiple blue-gray nodules and papules involving the head, trunk, and extremities at birth, the corresponding histopathologic findings, and genetic testing results.


Assuntos
Melanócitos/patologia , Nevo Azul/patologia , Nevo Pigmentado/patologia , Complexo de Carney/diagnóstico , Complexo de Carney/patologia , Pré-Escolar , Subunidade RIalfa da Proteína Quinase Dependente de AMP Cíclico/genética , Diagnóstico Diferencial , Feminino , Humanos , Lactente , Masculino , Melanócitos/metabolismo , Mutação , Nevo Azul/congênito , Nevo Pigmentado/congênito , Neoplasias Cutâneas/congênito , Neoplasias Cutâneas/patologia , Sequenciamento do Exoma/métodos
3.
PLoS Genet ; 12(2): e1005905, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26926673

RESUMO

Overexpression of SPARC, a collagen-binding glycoprotein, is strongly associated with tumor invasion through extracellular matrix in many aggressive cancers. SPARC regulates numerous cellular processes including integrin-mediated cell adhesion, cell signaling pathways, and extracellular matrix assembly; however, the mechanism by which SPARC promotes cell invasion in vivo remains unclear. A main obstacle in understanding SPARC function has been the difficulty of visualizing and experimentally examining the dynamic interactions between invasive cells, extracellular matrix and SPARC in native tissue environments. Using the model of anchor cell invasion through the basement membrane (BM) extracellular matrix in Caenorhabditis elegans, we find that SPARC overexpression is highly pro-invasive and rescues BM transmigration in mutants with defects in diverse aspects of invasion, including cell polarity, invadopodia formation, and matrix metalloproteinase expression. By examining BM assembly, we find that overexpression of SPARC specifically decreases levels of BM type IV collagen, a crucial structural BM component. Reduction of type IV collagen mimicked SPARC overexpression and was sufficient to promote invasion. Tissue-specific overexpression and photobleaching experiments revealed that SPARC acts extracellularly to inhibit collagen incorporation into BM. By reducing endogenous SPARC, we also found that SPARC functions normally to traffic collagen from its site of synthesis to tissues that do not express collagen. We propose that a surplus of SPARC disrupts extracellular collagen trafficking and reduces BM collagen incorporation, thus weakening the BM barrier and dramatically enhancing its ability to be breached by invasive cells.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/citologia , Colágeno Tipo IV/metabolismo , Osteonectina/metabolismo , Animais , Animais Geneticamente Modificados , Membrana Basal , Caenorhabditis elegans/genética , Caenorhabditis elegans/crescimento & desenvolvimento , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Matriz Extracelular/metabolismo , Regulação da Expressão Gênica , Mutação , Osteonectina/genética , Proteínas Proto-Oncogênicas c-fos/genética
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