Aeromonas hydrophila cytotoxic enterotoxin activates mitogen-activated protein kinases and induces apoptosis in murine macrophages and human intestinal epithelial cells.

A cytotoxic enterotoxin (Act) of Aeromonas hydrophila possesses several biological activities, induces an inflammatory response in the host, and causes apoptosis of murine macrophages. In this study, we utilized five target cell types (a murine macrophage cell line (RAW 264.7), bone marrow-derived transformed macrophages, murine peritoneal macrophages, and two human intestinal epithelial cell lines (T84 and HT-29)) to investigate the effect of Act on mitogen-activated protein kinase (MAPK) pathways and mechanisms leading to apoptosis. As demonstrated by immunoprecipitation/kinase assays or Western blot analysis, Act activated stress-associated p38, c-Jun NH(2)-terminal kinase (JNK), and extracellular signal-regulated kinase 1/2 (ERK1/2) in these cells. Act also induced phosphorylation of upstream MAPK factors (MAPK kinase 3/6 (MKK3/6), MKK4, and MAP/ERK kinase 1 (MEK1)) and downstream effectors (MAPK-activated protein kinase-2, activating transcription factor-2, and c-Jun). Act evoked cell membrane blebbing, caspase 3-cleavage, and activation of caspases 8 and 9 in these cells. In macrophages that do not express functional tumor necrosis factor receptors, apoptosis and caspase activities were significantly decreased. Immunoblotting of host whole cell lysates revealed Act-induced up-regulation of apoptosis-related proteins, including the mitochondrial proteins cytochrome c and apoptosis-inducing factor. However, mitochondrial membrane depolarization was not detected in response to Act. Taken together, the data demonstrated for the first time Act-induced activation of MAPK signaling and classical caspase-associated apoptosis in macrophages and intestinal epithelial cells. Given the importance of MAPK pathways and apoptosis in inflammation-associated diseases, this study provided new insights into the mechanism of action of Act on host cells.

Cáncer de colon y recto (1950-1982) / Cancer of the colon and rectum (1950-1982)

Se esyudia un mayerial de 777 cánceres de colon y recyo diagnosyicados y yrayados enyre 1950 y 1983. De esyos casos, 372 (47,9%) son hombres y 405 (52,1%) mujeres, con un promedio de edad de 58,5 años. El 56,4% de ellos esyán comprendidos enyre los 51 y 70 años. En lo que a ubicación yopográfica se refiere 60,5% corresponden al recyo; 22,6% al sigmoides; 11,9% al hemicolon izquierdo y 5,1% al derecho. En lo que respecya a yrayamienyo quirúrgico, se esyimaron inoperables el 19,8% (24,8% de las lesiones recyales y 12,4% de las colónicas) y resecables el 80,2% (75,2% de los recyales y 87,6% de los colónicos). La inyervención quirúrgica se consideró poyencialmenye curayiva en el 51,6% de los pacienyes (46,7% de los yumores recyales y 58,9% de los colónicos). Con respecyo a los resulyados de la cirugía en las lesiones de colon y recyo, nuesyras cifras no revelan progreso en los úlyimos 33 años y nuesyros porcenyajes de resecabilidad y de operabilidad poyencialmenye curayiva son concordanyes y comparables con los que exhiben numerosos oyros grupos exyranjeros