Many mutations of the NF1 gene have been reported in patients with neurofibromatosis type 1 (NF1); however, there have been no documented NF1 gene mutations in Japanese NF1 patients. In the present study, we used the polymerase chain reaction (PCR) and DNA sequencing analysis to characterize the NF1 gene in a 53-year-old Japanese patient with NF1 who suffered from neurofibroma, pheochromocytoma, and gastrointestinal stromal tumor (GIST). Direct sequence analyses revealed a single base substitution in the splicing donor site of intron 6 (IVS6 888+1, G --> A) in one NF1 allele, resulting in an altered splice site (ss) in the mutated allele. Splicing at the cryptic 5' ss in the mutated allele generated mRNA with an insertion of 60 nucleotides. In addition, we screened for mutations in exons 9, 11, 13, and 17 of the c-kit gene in GIST and the succinate dehydrogenase subunit D (SDHD) gene in the pheochromocytoma, but we did not detect any somatic mutations. We report here the first case of an NF1 patient with four neoplasms: neurofibroma, pheochromocytoma, astrocytoma and GIST. Our results suggest that the molecular pathogenesis of GISTs in NF1 patients is different from that in non-NF1 patients.

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Glicentin, the main component of enteroglucagon, has trophic effects on intestinal mucosa. It may also have an inhibitory effect on extraintestinal invasion of enteric bacteria. We have established an in vitro bioassay system for determining the effects of recombinant human glicentin on bacterial internalization by confluent enterocytes. An INT-407 cell line was serum-deprived for 2 days and was then treated on transwell filters for 24 h with a medium containing one of the following: glicentin 100 ng-1 microg/ml, glucagons-like peptide-2 (GLP-2) 1 microg/ml, 10% fetal bovine serum (FCS), or without any growth factors. Pure cultures of Salmonella enteritidis, Escherichia coli, and Enterococcus faecalis were introduced to the upper chambers of the filter units. Following 2 h of incubation the numbers of bacteria in the lower chambers were measured. Pretreatment of enterocytes with glicentin inhibited bacterial internalization compared to untreated or GLP-2 enterocytes. Glicentin was associated with inhibition of enterocyte internalization of enteric bacteria by a mechanism that might be related to the integrity of the enterocyte adhesive junctions and tight junctions and to the production of sIgA. Glicentin seems to have a function as a barrier-sustaining agent that inhibits extraintestinal invasion of enteric bacteria.