RESUMO
p53 plays a central role in neuronal cell death resulting from acute injury or disease. To define the pathway by which p53 triggers apoptosis, we used microarray analysis to identify p53 target genes specifically upregulated during apoptosis but not cell cycle arrest. This analysis identified a small subset of targets highly selective for the p53 apoptotic response, including Siva, a proapoptotic protein whose function is not well understood. Siva's expression pattern suggests that it plays an instructive role in apoptosis, and accordingly, we demonstrate that Siva is essential for p53-dependent apoptosis in cerebellar granule neurons. In addition, we determine that endogenous Siva is associated with the plasma membrane and that Caspase-8 and Bid are important for neuronal apoptosis. Our studies highlight the participation of membrane signaling events in p53's apoptotic program in primary neurons and have significant implications for understanding the mechanisms underlying pathogenesis after neuronal injury and in neurodegenerative diseases.
Assuntos
Apoptose/fisiologia , Encefalopatias/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Degeneração Neural/genética , Neurônios/metabolismo , Proteína Supressora de Tumor p53/genética , Animais , Animais Recém-Nascidos , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Proteína Agonista de Morte Celular de Domínio Interatuante com BH3/metabolismo , Encefalopatias/metabolismo , Encefalopatias/fisiopatologia , Caspase 8/metabolismo , Membrana Celular/metabolismo , Células Cultivadas , Cerebelo/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Camundongos , Camundongos Knockout , Degeneração Neural/metabolismo , Degeneração Neural/fisiopatologia , Análise de Sequência com Séries de Oligonucleotídeos , Transdução de Sinais/fisiologia , Proteína Supressora de Tumor p53/metabolismoRESUMO
Social support, stress, health locus of control, active and avoidance coping, and depression were studied with 107 married couples in which one partner had a chronic obstructive airway disease (mean age = 62 years old). Differences between couples were evident when gender of the patient was assessed. Female patient couples that were older appeared more at risk than male patient couples for distress. In the analyses of spouse depression, gender moderated the relation of coping, social support, and health locus of control with depression. For patients, coping and social support were directly related to depression rather than moderated by gender. Implications for prevention and future research are discussed.
Assuntos
Adaptação Psicológica , Depressão/psicologia , Identidade de Gênero , Pneumopatias Obstrutivas/psicologia , Papel do Doente , Cônjuges/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Depressão/diagnóstico , Feminino , Humanos , Controle Interno-Externo , Masculino , Pessoa de Meia-Idade , Apoio SocialRESUMO
The American dog tick, Dermacentor variabilis (Say), until recently was recorded only from the southeastern and southwestern counties of Pennsylvania. Since 1968, this species has expanded its range and is reported from 63 of Pennsylvania's 67 counties. This range extension is a matter of concern to the medical community and to physicians throughout Pennsylvania, particularly those with practices in areas where this tick was previously unknown and who may not be familiar with the symptoms of Rocky Mountain spotted fever.
Assuntos
Demografia , Dermacentor , Insetos Vetores , Animais , Incidência , Pennsylvania/epidemiologia , Febre Maculosa das Montanhas Rochosas/epidemiologiaRESUMO
In order to determine if there were differences in individuals who were currently obese, previously obese now average, and always average, a battery of behavioral and personality measures were administered which included the assessment of self-concept, self-control, health locus of control, comparative reinforcement hierarchy and various activities. Significant differences were obtained in physical self-concept; time spent in vigorous activity, passive activity, with friends and social activities; and the reinforcement value of eating, time with friends or family, and taking it easy. The possible significance of these findings was discussed in terms of maintaining factors in obesity and treatment suggestions.
Assuntos
Obesidade/psicologia , Personalidade , Autoimagem , Adolescente , Adulto , Feminino , Humanos , Controle Interno-Externo , Masculino , Pessoa de Meia-Idade , Obesidade/terapia , Esforço Físico , Ajustamento SocialRESUMO
The effects of single oral doses of 10, 15, or 30 mg of prednisone on circulating mononuclear cells, autologous MLR, mitogen responses, and allogeneic MLR were studied in healthy volunteers. Doses as low as 10 mg were immunosuppressive, causing diminution of circulating T cells and monocytes, and significant reduction in autologous but not allogeneic MLR responses. These effects were maximal 6 hr after drug administration and gone by 24 hr. Autologous MLR responses were particularly sensitive to the effects of prednisone being significantly and consistently suppressed 2 hr after drug administration, before significant cell redistribution had occurred. Macrophage-enriched stimulating cells were more easily suppressed than responding T cells. Since the autologous MLR may be important in in vivo regulation of immune responses, its reduction by low-dose glucocorticoids may be of clinical relevance. This suppressive effect must be considered in studies of the autologous MLR in patients receiving glucocorticoid therapy.