RESUMO
The promise of gene therapy for health care will not be realized until gene delivery systems are capable of achieving efficient, cell-specific gene delivery in vivo. Here we describe an adenoviral system for achieving cell-specific transgene expression in pulmonary endothelium. The combination of transductional targeting to a pulmonary endothelial marker (angiotensin-converting enzyme, ACE) and an endothelial-specific promoter (for vascular endothelial growth factor receptor type 1, flt-1) resulted in a synergistic, 300,000-fold improvement in the selectivity of transgene expression for lung versus the usual site of vector sequestration, the liver. This combined approach should be useful for the design of other gene delivery systems.
Assuntos
Técnicas de Transferência de Genes , Terapia Genética/métodos , Transcrição Gênica , Transdução Genética , Transgenes , Adenoviridae/genética , Animais , Linhagem Celular , Fatores de Crescimento Endotelial/genética , Endotélio/metabolismo , Endotélio Vascular/metabolismo , Vetores Genéticos , Imuno-Histoquímica , Fígado/metabolismo , Luciferases/metabolismo , Pulmão/metabolismo , Linfocinas/genética , Masculino , Camundongos , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/metabolismo , Regiões Promotoras Genéticas , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio VascularRESUMO
The typical family constellation in this study of 14 cases of incest was that of a chronically depressed mother, an alcoholic and violent father or stepfather, and an eldest daughter who was forced to assume many of her mother's responsibilities, with ensuing role confusion. The authors stress the need for physicians to be alert to the possibility of incest in such high-risk families.
Assuntos
Características da Família , Incesto , Adolescente , Alcoolismo/genética , Criança , Pré-Escolar , Depressão/genética , Feminino , Humanos , Masculino , Risco , ViolênciaRESUMO
Acute febrile neutrophilic dermatosis (Sweet's syndrome) is a rare inflammatory disease of unknown cause characterized by painful, erythematous plaques and a dermal infiltrate of mature neutrophils. Associated systemic disease is a common finding in patients with Sweet's syndrome, and in fact determines the prognosis; therefore, the diagnosis of Sweet's syndrome warrants a thorough medical evaluation. We found only 17 reported cases of Sweet's syndrome in children. Two cases of Sweet's syndrome in children are presented; these cases are typical, except for the tibial pain in the first patient and the marked leukocytosis in the second patient. Both patients responded promptly to systemic corticosteroid therapy, although both had relapse.