The origin and neoplastic potential of gastric epithelial that is comparable with the adenoma-carcinoma sequence polyps remains an area of great interest, and treatment in the colorectum. 7 In the intestinal type of stomach choices are a topic of controversy. This report de-cancer, an accumulation of genetic mutations leading to scribes a patient diagnosed with three concurrent hyoncogene activation and loss of tumor suppressor gene perplastic gastric polyps that were studied for genetic function may be associated with a gastric dysplasia-carcialterations. The polyps were investigated for alternoma sequence. However, the specific genetic changes ations in the K-ras oncogene and the p53 tumor supaccompanying this sequence are less well defined. 8 pressor gene and for p21 WAF1/Cip1 and MDM2 protein Activation of ras oncogenes, a frequent finding in colooverexpression. In addition, loss of heterozygosity at rectal neoplasms, is rare in the stomach, although it was several loci that are frequently involved in human canreported in a subset of patients at high risk for stomach cer was analyzed, microsatellite instability, a hallmark cancer. 9,10 Activation of the K-ras oncogene by codon 12 of the ''mutator'' phenotype, was determined, and Eppoint mutations is a common and relatively early event stein-Barr virus infection was investigated. All separate areas from the three independent polyps harbored in colorectal neoplasms. Alterations in the p53 tumor accompanied by allelic loss of the remaining functional markers were observed. The results strongly favor a p53 allele. 13 The normal (wild-type) p53 protein, but clonal origin of the three independent gastric polyps not the altered p53 protein, binds specifically to DNA and support the notion that these hyperplastic polyps and acts as a transcription factor for several genes. 14 One may carry a risk for malignancy.of these genes, called WAF1 or Cip1, encodes a 21-kilodalton protein (p21 WAF1/Cip1 ) that is a potent inhibitor for several cyclin-dependent kinases that control progres-

SUMMARYInflammatory bowel disease is associated with mucosal neutrophil recruitment and activatation, mediated in part by arachidonic acid metabolites. G-CSF attenuates the immune response to sepsis and ameliorates glycogen storage disease Ib-related colitis. These actions may be effected through the shedding of neutrophil adhesion molecules, or inhibition of proinflammatory mediator synthesis. Immune complex colitis was used to evaluate the effect of rhG-CSF on colonic mucosal inflammation, neutrophil recruitment and the generation of eicosanoids. Immune complex colitis was induced in White New Zealand rabbits. Animals were pretreated with rhG-CSF either 24 h before induction, or at induction, with dosages of 50 and 200 g/kg. rhG-CSF caused a time-and dose-dependent neutrophilia in all animals. Pretreatment with rhG-CSF resulted in increased tissue myeloperoxidase levels, despite a histologically similar mucosal polymorphonuclear cell infiltrate between treated and control colitis groups. Leukotriene B 4 (LTB 4 ) and thromboxane B 2 (TXB 2 ) dialysis fluid levels were lower in treated animals, in particular in the groups receiving two doses (LTB 4 : both P < 0 : 01; TXB 2 : both P < 0 : 01. Prostaglandin E 2 (PGE 2 ) levels in dialysis fluid of the rhG-CSF-treated animals showed no difference from controls. In this model of experimental colitis, high-dose therapy with G-CSF resulted in a marked decrease of proinflammatory mediators, but mucosal generation of the protective PGE 2 was preserved. These results suggest that prolonged high-dose therapy with G-CSF may have anti-inflammatory effects in colitis.

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These results suggest that blockade of CD11b/CD18-mediated mucosal neutrophil recruitment may form part of a strategy for targeted therapeutic intervention in inflammatory bowel disease.

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