RESUMEN
Lung infections with Pseudomonas aeruginosa and other pathogens in cystic fibrosis (CF) cause progressive airway obstruction and tissue damage, the predominant cause of morbidity and mortality in CF. We investigated whether a recombinant adeno-associated virus type 5 (AAV5) vector expressing murine interleukin (IL)-10 (AAV5.Cbeta-mIL-10), a regulatory/anti-inflammatory cytokine, could decrease airway inflammation in IL-10 knockout mice chronically infected with mucoid P. aeruginosa. Mice that received AAV5.Cbeta-mIL10 through intratracheal inoculation produced IL-10 at an average of 25 000 pg/ml in the epithelial lining fluid (ELF) and 12 000 pg/g-lung tissue 6 weeks post-vector delivery, significantly higher levels than in placebo-treated mice. At 3 days post-infection, proinflammatory cytokines (IL-1beta, tumor necrosis factor (TNF)-alpha, macrophage inhibitory protein (MIP)-1alpha and (KC) in the ELF and lung homogenate were decreased (1-9 folds) in the AAV5.Cbeta-mIL10-treated mice accompanied by less pronounced and more localized neutrophil infiltration in lung sections, when compared with placebo-treated mice. These results suggest that AAV5.Cbeta-mIL10 induces IL-10 levels in the lungs mediating a significant anti-inflammatory response and making AAV-IL-10 gene transfer a potentially useful therapy in the treatment of CF lung disease.
Asunto(s)
Fibrosis Quística/terapia , Terapia Genética/métodos , Interleucina-10/genética , Neumonía Bacteriana/terapia , Infecciones por Pseudomonas/terapia , Pseudomonas aeruginosa , Animales , Dependovirus , Vectores Genéticos , Intubación Intratraqueal , Ratones , Ratones Noqueados , Neutrófilos/microbiologíaRESUMEN
The effectiveness of Hutt's Bender Gestalt scoring system in screening for schizophrenia, depression, and brain damage was investigated in a sample of mixed, psychiatric inpatients. Fifteen patients represented each diagnostic category. After an examination of each patient's Bender Gestalt protocol according to Hutt's criteria, it was found that the true positive and true negative success rates of the screening procedures for depression and brain damage were significantly higher than corresponding base rates. The Lacks Bender Gestalt screening method for brain damage was no more successful than the Hutt method in identifying true positives and true negatives. With the brain-damaged patients excluded, Hutt's screening procedures for both depression and schizophrenia resulted in significantly high rates of successful identification of true positives and true negatives. Moreover, these rates did not significantly differ from those determined by patients' Minnesota Multiphasic Personality Inventory (MMPI) T scores on corresponding scales.