RESUMEN
Mice lacking suppressor of cytokine signaling-1 (SOCS1) develop a complex fatal neonatal disease. In this study, SOCS1-/- mice were shown to exhibit excessive responses typical of those induced by interferon gamma (IFNgamma), were hyperresponsive to viral infection, and yielded macrophages with an enhanced IFNgamma-dependent capacity to kill L. major parasites. The complex disease in SOCS1-/- mice was prevented by administration of anti-IFNgamma antibodies and did not occur in SOCS1-/- mice also lacking the IFNgamma gene. Although IFNgamma is essential for resistance to a variety of infections, the potential toxic action of IFNgamma, particularly in neonatal mice, appears to require regulation. Our data indicate that SOCS1 is a key modulator of IFNgamma action, allowing the protective effects of this cytokine to occur without the risk of associated pathological responses.
Asunto(s)
Proteínas Portadoras/fisiología , Regulación del Desarrollo de la Expresión Génica , Interferón gamma/antagonistas & inhibidores , Proteínas Represoras , Transducción de Señal , Infecciones por Alphavirus/mortalidad , Infecciones por Alphavirus/prevención & control , Animales , Susceptibilidad a Enfermedades , Interferón gamma/farmacología , Interferón gamma/fisiología , Leishmania major/inmunología , Leishmaniasis/mortalidad , Leishmaniasis/prevención & control , Linfopenia/mortalidad , Linfopenia/prevención & control , Macrófagos/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Ratones Mutantes , Virus de los Bosques Semliki/inmunología , Virus de los Bosques Semliki/metabolismo , Proteína 1 Supresora de la Señalización de Citocinas , Proteínas Supresoras de la Señalización de CitocinasRESUMEN
No currently used diagnostic test is an accurate predictor of patients who will develop morbidity or mortality from cardiac contusion. In a prospective study we used gated cardiac radionuclide angiography to assess cardiac function in 30 patients with blunt chest trauma, and we compared the results of this test with those of other diagnostic studies for cardiac contusion to determine whether gated angiography is a more accurate predictor of serious cardiac injury. Diagnostic tests included the following: serial electrocardiograms (ECG), serial creatine phosphokinase muscle-brain isoenzyme (CPK-MB) and lactic dehydrogenase (LDH) isoenzymes, gated cardiac radionuclide angiography, and technetium-99m (Tc-99m) pyrophosphate scintigraphy. Abnormal studies were present in 26 patients; 22 showed abnormalities in CPK-MB, 19 on ECG, and five on gated scan. No patient demonstrated an abnormal Tc-99m pyrophosphate scan or abnormal elevation of LDH isoenzyme. Although no diagnostic test was predictive of morbidity and mortality, CPK-MB isoenzyme was the only test to correlate with morbidity and mortality. Morbidity and mortality correlated most closely with the number of associated major injuries and the presence of hypotension or hypoxia.
