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B C Lewis

Publications and source records attributed to B C Lewis.

26 records · Page 2Linked to original sources

The Ewing's sarcoma EWS/FLI-1 fusion gene encodes a more potent transcriptional activator and is a more powerful transforming gene than FLI-1.

EWS/FLI-1 is a chimeric protein formed by a tumor-specific 11;22 translocation found in both Ewing's sarcoma and primitive neuroectodermal tumor of childhood. EWS/FLI-1 has been shown to be a potent transforming gene, suggesting that it plays an important role in the genesis of these human tumors. We now demonstrate that EWS/FLI-1 has the characteristics of an aberrant transcription factor. Subcellular fractionation experiments localized the EWS/FLI-1 protein to the nucleus of primitive neuroectodermal tumor cells. EWS/FLI-1 specifically bound in vitro an ets-2 consensus sequence similarly to normal FLI-1. When coupled to a GAL4 DNA-binding domain, the amino-terminal EWS/FLI-1 region was a much more potent transcriptional activator than the corresponding amino-terminal domain of FLI-1. Finally, EWS/FLI-1 efficiently transformed NIH 3T3 cells, but FLI-1 did not. These data suggest that EWS/FLI-1, functioning as a transcription factor, leads to a phenotype dramatically different from that of cells expressing FLI-1. EWS/FLI-1 could disrupt normal growth and differentiation either by more efficiently activating FLI-1 target genes or by inappropriately modulating genes normally not responsive to FLI-1.

3T3 Cells↗

Creation of a yeast artificial chromosome fragmentation vector based on lysine-2.

Yeast artificial chromosome (YAC) fragmentation vectors have proven to be useful reagents for mapping and modifying YAC clones through homologous recombination. Such vectors can be employed to remove a noncontiguous sequence present in chimeric YAC clones. However, previous fragmentation vectors have been based on auxotrophies not present in the background of most recombinant YAC libraries, which therefore makes them difficult to use. We have constructed an acentric YAC deletion vector pBCL that is fully compatible with AB 1380, the yeast host used in the majority of human total genomic YAC libraries. Transformation of three unrelated YACs with linearized pBCL yielded derivative clones with the expected phenotype at rates of 27%-49%. Analysis of a random cohort of these clones by pulsed-field gel electrophoresis and Southern blotting revealed single deleted structures in 31 of 34 clones. Using this vector, a nested set of deletion derivatives can efficiently and reliably be generated from human recombinant YAC clones.

Chromosomes, Fungal↗

Circulatory support in infants with post-cardiopulmonary bypass left ventricular dysfunction using a left ventricular assist device.

Extracorporeal membrane oxygenation has been advocated as the most appropriate mode of circulatory support in the paediatric age group for post-cardiopulmonary bypass ventricular dysfunction. The results in infants who have predominantly left ventricular failure, or who require such support in order to be weaned off bypass, have been disappointing. Three infants with severe left ventricular dysfunction following cardiopulmonary bypass for correction of congenital heart defects have been managed with a left ventricular assist device. Two required this form of circulatory support in order to be weaned from full bypass while in the third infant it was instituted for progressive left ventricular dysfunction postoperatively. All three were less than 10 kg in weight. Left atrial appendage to aortic bypass was effected using a closed loop circuit with a constrained vortex pump (Biomedicus). Duration of support ranged between 40 and 146 h. One infant made a complete recovery and was able to be discharged home 20 days postoperatively. Another made a circulatory recovery such that both mechanical and inotropic support could be discontinued but had sustained massive neurological damage. The third died of progressive left ventricular dysfunction. This experience with a left ventricular assist device demonstrates that it is technically feasible in small infants, and can be performed to good effect in infants with predominant left ventricular dysfunction following cardiac surgery. It may well be more appropriate than extracorporeal membrane oxygenation in this group of patients.

Cardiac Output, Low↗

Intestinal crypt lesions associated with protein-losing enteropathy in the dog.

Six dogs were diagnosed with protein losing enteropathy (PLE). There was no evidence of inappropriate inflammatory infiltrates or lymphangiectasia in multiple mucosal biopsies of the small intestine of 4 of the dogs. The 5th and 6th dogs had obvious lymphangiectasia and a moderate infiltrate of inflammatory cells in the intestinal mucosa. All 6 dogs had a large number of dilated intestinal crypts that were filled with mucus, sloughed epithelial cells, and/or inflammatory cells. Whether PLE occurs in these dogs because of protein lost from the dilated crypts into the intestinal lumen or whether the dilated crypts are a mucosal reaction due to another undetermined lesion that is responsible for alimentary tract protein loss is unknown. However, when large numbers of dilated intestinal crypts are present, they appear to be associated with PLE even if there are no other remarkable lesions in the intestinal mucosa.

Animals↗