[A retrospective study of 91 injections of botulinus toxin into the upper sphincter of the oesophagus]. / Analyse rétrospective de 91 injections de toxine botulique dans le sphincter supérieur de l'oesophage.

OBJECTIVE: To evaluate the results of botulinus toxin in dysphagia arising in the upper sphincter of the oesophagus. MATERIALS AND METHODS: Since June 1995, 64 patients have had botulinus toxin injected into the upper sphincter of the oesophagus for major swallowing disorders. All cases were treated in the dysphagia service, and underwent clinical assessment, video-swallow screening, and swallowing therapy. The patient cohort included various pathological groups--neurological (vascular accident, head injury, cranial nerve disorders, degenerative diseases), postoperative (surgery for carcinoma of the laryngo-pharynx), and functional, whether purely idiopathic or attributable. RESULTS AND CONCLUSIONS: Global analysis of the results shows that botulinus toxin has good efficacy in relaxing the upper sphincter of the oesophagus; this does not always lead to recovery of normal swallowing, but can bring about improvement by assisting in the therapeutic management of the swallowing problem, and in improving the dietary intake.

c-myc box II mutations in Burkitt's lymphoma-derived alleles reduce cell-transformation activity and lower response to broad apoptotic stimuli.

In addition to c-myc rearrangement, over 50% of Burkitt's lymphoma cases present clustered mutations in exon 2, where many of the functional activities of c-Myc protein are based. This report describes the functional consequences induced by tumour-derived c-myc mutations located in c-myc box II. Two mutated alleles were studied, focusing on the P138C mutation, and compared to wild-type c-myc. The c-Myc transformation, transactivation and apoptosis activities were explored based on cells over-expressing c-Myc. While the transcriptional activation activity was not affected, our experiments exploring the anchorage-independent growth capacity of c-Myc-transfected Rat1a cells showed that c-Myc box II mutants were less potent than wild-type c-Myc in promoting cell transformation. Considering the possibility that these mutations could be interfering with the ability of c-Myc to promote apoptosis, we tested c-Myc-transfected Rat1a fibroblasts under several conditions: serum deprivation-, staurosporine- and TNFalpha-induced cell death. Interestingly, the mutated alleles were characterized by an overall decrease in ability to mediate apoptosis. Our study indicates that point mutations located in c-Myc box II can decrease the ability of the protein to promote both transformation and apoptosis without modifying its transactivating activity.