Discovery of SMAD4 promoters, transcription factor binding sites and deletions in juvenile polyposis patients

Inactivation of SMAD4 has been linked to several cancers and germline mutations cause juvenile polyposis (JP). We set out to identify the promoter(s) of SMAD4, evaluate their activity in cell lines and define possible transcription factor binding sites (TFBS). 5′-rapid amplification of cDNA ends (5′-RACE) and computational analyses were used to identify candidate promoters and corresponding TFBS and the activity of each was assessed by luciferase vectors in different cell lines. TFBS were disrupted by site-directed mutagenesis (SDM) to evaluate the effect on promoter activity. Four promoters were identified, two of which had significant activity in several cell lines, while two others had minimal activity. In silico analysis revealed multiple potentially important TFBS for each promoter. One promoter was deleted in the germline of two JP patients and SDM of several sites led to significant reduction in promoter activity. No mutations were found by sequencing this promoter in 65 JP probands. The predicted TFBS profiles for each of the four promoters shared few transcription factors in common, but were conserved across several species. The elucidation of these promoters and identification of TFBS has important implications for future studies in sporadic tumors from multiple sites, and in JP patients

Hepatitis por Rotavirus. A propósito de un caso

Introducción: La infección por rota virus se ha reconocido como un patógeno en el humano y causante de enfermedad diarreica grave; la infección se ha asociado con meningitis aséptica, enterocolitis necrotizante, miositis aguda , abscesos hepáticos, neumonía, enfermedad de Kawasaki , síndrome de muerte súbita y enfermedad de Crohn. En este caso se informa la asociación con hepatitis infecciosa. Caso Clínico: Masculino, con colitis alérgica a las proteínas de la leche de vaca y de la soya, desde el nacimiento. Al mes y medio presenta enfermedad diarreica por rota virus asociada a hepatitis. Conclusiones: Tradicionalmente se ha considerado que es una infección del intestino delgado y que todos los eventos fisiopatologicos son el resultado de este tipo de lesión y de la intolerancia alimentaria que provoca a nivel local, sin embargo se han informado enfermedades que se presentan en otros órganos, como respuesta a la infección viral del sistema digestivo. En esta ocasión la invasión por el virus provoca daño hepático