RESUMO
The role of nitric oxide in N-methyl-D-aspartate (NMDA) neurotoxicity was investigated in murine cortical cell cultures. Exposure of cultures to 300 microM NMDA for 5 min resulted in death of 50-80% of neurons over the subsequent 24 h. This injury was not attenuated by hemoglobin, the nitric oxide synthase (NOS) inhibitors NG monomethyl-L-arginine (MMA) or N omega-nitro-L-arginine (NA), or L-arginine depletion. Hemoglobin and NOS inhibitors consistently prevented the increase in cyclic guanosine monophosphate (cGMP) seen after NMDA exposure. These results suggest that NMDA neurotoxicity in this cell culture system is mediated, at least in part, by mechanisms other than NOS activation.
Assuntos
Córtex Cerebral/efeitos dos fármacos , Hemoglobinas/farmacologia , N-Metilaspartato/toxicidade , Neurotoxinas/farmacologia , Óxido Nítrico/antagonistas & inibidores , Animais , Células Cultivadas , Córtex Cerebral/citologia , Maleato de Dizocilpina/farmacologia , Camundongos , Degeneração Neural , Neurônios/efeitos dos fármacos , Óxido Nítrico/metabolismoRESUMO
Id1 is frequently overexpressed in many cancer cells, but the functional significance of these findings is not known. To determine if Id1 could contribute to the development of hematopoietic malignancy, we reconstituted mice with hematopoietic cells overexpressing Id1. We showed for the first time that deregulated expression of Id1 leads to a myeloproliferative disease in mice, and immortalizes myeloid progenitors in vitro. In human cells, we demonstrate that Id genes are expressed in human acute myelogenous leukemia cells, and that knock down of Id1 expression inhibits leukemic cell line growth, suggesting that Id1 is required for leukemic cell proliferation. These findings established a causal relationship between Id1 overexpression and hematologic malignancy. Thus, deregulated expression of Id1 may contribute to the initiation of myeloid malignancy, and Id1 may represent a potential therapeutic target for early stage intervention in the treatment of hematopoietic malignancy.
Assuntos
Células-Tronco Hematopoéticas/citologia , Proteína 1 Inibidora de Diferenciação/fisiologia , Transtornos Mieloproliferativos/etiologia , Animais , Células da Medula Óssea/citologia , Diferenciação Celular , Linhagem Celular Tumoral , Proliferação de Células , Quinases Ciclina-Dependentes/antagonistas & inibidores , Fator Estimulador de Colônias de Granulócitos/farmacologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Humanos , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Among 37,857 operations in a general surgical department (1965-1975), 205 interventions on the small intestine were necessary- enterotomies, oversuturing, amputations and resections. The operations are evaluated with regard to etiology, clinical aspects and operative technique.