RESUMO
Immune responses against an introduced transgenic protein are a potential risk in many gene replacement strategies to treat genetic disease. We have developed a gene delivery approach for hemophilia B based on lentiviral expression of human factor IX in purified hematopoietic stem cells. In both normal C57Bl/6J and hemophilic 129/Sv recipient mice, we observed the production of therapeutic levels of human factor IX, persisting for at least a year with tolerance to human factor IX antigen. Secondary and tertiary recipients also demonstrate long-term production of therapeutic levels of human factor IX and tolerance, even at very low levels of donor chimerism. Furthermore, in hemophilic mice, partial functional correction of treated mice and phenotypic rescue is achieved. These data show the potential of a stem cell approach to gene delivery to tolerize recipients to a secreted foreign transgenic protein and, with appropriate modification, may be of use in developing treatments for other genetic disorders.
Assuntos
Fator IX/genética , Terapia Genética/métodos , HIV-1/genética , Hemofilia B/terapia , Transplante de Células-Tronco/métodos , Animais , Antígenos/imunologia , Células Cultivadas , Fator IX/metabolismo , Expressão Gênica , Doenças Genéticas Inatas/genética , Doenças Genéticas Inatas/terapia , Genótipo , Proteínas de Fluorescência Verde/genética , Hemofilia B/sangue , Humanos , Tolerância Imunológica , Camundongos , Camundongos Endogâmicos C57BL , Fenótipo , Células-Tronco/metabolismo , Células-Tronco/virologia , Fatores de Tempo , Transdução Genética/métodos , TransgenesRESUMO
Damien and John Keown claim that there is important common ground between Buddhism and Christianity on the issue of euthanasia and that both traditions oppose it for similar reasons in order to espouse a "sanctity of life" position. I argue that the appearance of consensus is partly created by their failure to specify clearly enough certain key notions in the argument: particularly Buddhism, euthanasia and the sanctity of life. Once this is done, the Keowns' central claims can be seen to be either false or only restrictedly true.
Assuntos
Budismo , Cristianismo , Comparação Transcultural , Eutanásia , Religião e Medicina , Teologia , Valor da Vida , Consenso , Eutanásia Ativa Voluntária , Direitos Humanos , HumanosRESUMO
We argue that if a terminally ill patient wants to know the truth about his or her condition, and the patient's doctor possesses that information, then the doctor is morally obliged to tell the truth. The argument is not based on any supposed right to information (even information about oneself); nor on any supposed moral obligation to tell the truth; nor on any supposed property rights the patient might have. Rather, the argument is based on the very principle usually invoked to license deception: the harm principle (that doctors ought to take that course of action which does least harm to the patient).
Assuntos
Ética Médica , Assistência Terminal/psicologia , Revelação da Verdade , Atitude Frente a Morte , Humanos , Obrigações Morais , Defesa do PacienteAssuntos
Sistema Enzimático do Citocromo P-450/análise , Hexosiltransferases/análise , Fígado/enzimologia , Microssomos Hepáticos/enzimologia , Fenobarbital/farmacologia , Bilirrubina/sangue , Biópsia , Colelitíase/enzimologia , Indução Enzimática/efeitos dos fármacos , Humanos , Laparotomia , Cuidados Pré-OperatóriosRESUMO
Two series of patients observed clinically and by phlebography suggest that one agent known to produce a reduction in platelet aggregation in vitro might be useful in reducing the incidence of deep venous thrombosis and pulmonary embolism postoperatively. The agent used in this study was hydroxychlorquine sulphate.
