RESUMEN
Previous research has shown an association between cognitive control deficits and problematic behavior such as antisocial behavior and substance use, but little is known about the predictive value of cognitive control for treatment outcome. The current study tests whether selected markers of baseline cognitive control predict (1) treatment completion of a day treatment program involving a combination of approaches for multiproblem young adults and (2) daytime activities a year after the start of treatment, over and above psychological, social, and criminal characteristics. We assessed individual, neurobiological, and neurobehavioral measures, including functional brain activity during an inhibition task and two electroencephalographic measures of error processing in 127 male multiproblem young adults (age 18-27 years). We performed two hierarchical regression models to test the predictive power of cognitive control for treatment completion and daytime activities at follow-up. The overall models did not significantly predict treatment completion or daytime activities at follow-up. However, activity in the anterior cingulate cortex (ACC) during response inhibition, years of regular alcohol use, internalizing problems, and ethnicity were all significant individual predictors of daytime activity at follow-up. In conclusion, cognitive control could not predict treatment completion or daytime activities a year after the start of treatment over and above individual characteristics. However, results indicate a direct association between brain activity during response inhibition and participation in daytime activities, such as work or school, after treatment. As adequate baseline inhibitory control is associated with a positive outcome at follow-up, this suggests interventions targeting cognitive control might result in better outcomes at follow-up.
Asunto(s)
Síntomas Conductuales/fisiopatología , Síntomas Conductuales/terapia , Electroencefalografía , Función Ejecutiva/fisiología , Neuroimagen Funcional , Giro del Cíngulo/fisiología , Inhibición Psicológica , Evaluación de Resultado en la Atención de Salud , Desempeño Psicomotor/fisiología , Adolescente , Adulto , Síntomas Conductuales/etnología , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Masculino , Psicoterapia , Instituciones Académicas , Trabajo , Adulto JovenRESUMEN
In this study we investigated the capacity of rat IgA to activate complement (C) in vivo in a rat model. Rat monomeric (m-), dimeric (d-) and polymeric (p-) IgA MoAbs were injected intravenously and assessed for deposition of C3 and C4 on IgA. By ELISA it was shown that both d- and p-IgA bound C3 whereas no binding of C3 by m-IgA was observed. Polymeric IgA was more efficient in binding of C3 as compared with d-IgA. However, in haemolytic assays no consistent decrease of plasma complement levels was observed except for dimeric IgA which induced a marginal consumption of AP50. When rats were pre-treated with cobra venom factor (CVF) to deplete C3, no C3 deposition was found on m-, d- or p-IgA. Neither m- nor d- or p-IgA was able to bind C4 in vivo. In agreement with the results described above, large sized polymeric IgA was shown to be taken up by Kupffer cells (KC) together with C3. No C3 was detected when rats were depleted of C using CVF. Taken together, the experimental data suggest that d- and p-IgA are able to activate C via the alternative pathway in vivo.
Asunto(s)
Activación de Complemento , Inmunoglobulina A/inmunología , Animales , Complemento C3/metabolismo , Técnica del Anticuerpo Fluorescente , Inmunoglobulina G/inmunología , Masculino , Ratas , Ratas EndogámicasRESUMEN
In a previous study we have demonstrated that heat-killed Staphylococcus aureus opsonized with either purified human serum IgA or secretory IgA (sIgA) can induce a respiratory burst (measured as H2O2 release) in human polymorphonuclear leucocytes (PMN; Gorter et al., 1987). In the present study we have investigated whether opsonization of IgA-coated staphylococci with complement has an additional effect on the H2O2 release of PMN. It was demonstrated that staphylococci coated with IgA (or sIgA) and subsequently opsonized with complement induced at least a two-fold increase in the specific H2O2 release compared with bacteria coated with IgA (or sIgA) alone (P less than 0.05 and P less than 0.02, respectively). The co-operative effect of IgA and complement was also observed in the presence of 10 mM ethyleneglycoltetraacetic acid containing 5 mM MgCl2 (MgEGTA), suggesting that activation of the alternative pathway of complement is sufficient to exert this effect. Using D-deficient serum as a source of complement we could demonstrate that activation of the alternative pathway is essential for the co-operative effect of complement and IgA. The increase in specific H2O2 release caused by complement was found to be dependent on the amount of IgA initially used to opsonize the bacteria. Finally the co-operative effect of IgA and complement was not restricted to one IgA subclass, because an additional opsonization of S. aureus coated with sIgA1 or sIgA2 with complement resulted in both cases in a statistically significant enhanced specific H2O2 release by PMN (P less than 0.05).
Asunto(s)
Proteínas del Sistema Complemento/fisiología , Peróxido de Hidrógeno/metabolismo , Inmunoglobulina A/fisiología , Neutrófilos/metabolismo , Complemento C3/fisiología , Vía Alternativa del Complemento , Humanos , Consumo de OxígenoRESUMEN
The aim of the present study was to investigate whether corpuscular immune complexes containing human IgA were able to interact with human polymorphonuclear leucocytes (PMN). As a model for corpuscular IgA immune complexes (IgA IC), heat-killed Staphylococcus aureus (S. aureus) opsonized with either purified human serum IgA or purified secretory IgA (sIgA) isolated from human colostrum was used. In order to determine the capacity of IgA and sIgA to opsonize S. aureus the phagocytosis of these IgA IC by PMN was measured. S. aureus opsonized with IgA, sIgA, IgG, heat-inactivated serum or fresh serum was ingested by 23 +/- 8%; 28 +/- 9%; 39 +/- 7%; 31 +/- 10% and 78 +/- 10% of the PMN (S. aureus:PMN = 10:1, n = 4), respectively. These results were significantly different (P less than 0.05) from the percentage obtained with unopsonized S. aureus (9 +/- 3%), indicating that IgA and sIgA induce ingestion of S. aureus. The phagocytic index for PMN incubated with S. aureus opsonized with sIgA (231) was higher than for S. aureus opsonized with IgA (119), indicating a better uptake of S. aureus opsonized with sIgA in our system. Bacteria opsonized with either IgA or sIgA were also capable of triggering H2O2 release of PMN in a dose-dependent manner. The H2O2 release by PMN triggered with S. aureus opsonized with IgA could not be inhibited with a F(ab')2 anti-Fe gamma receptor monoclonal antibody, whereas the H2O2 release triggered with S. aureus opsonized with IgG was fully inhibited. Soluble heat-aggregated IgA (AIgA) also induced H2O2 release of PMN, suggesting that the IgA itself is essential for the induction of a respiratory burst.