Fumonisin B1 (FB1) is a carcinogenic mycotoxin produced by the fungus Fusarium moniliforme in corn. Feeding of FB1 to rats causes acute liver injury, chronic liver injury progressing to cirrhosis, and sometimes terminates in hepatocellular carcinoma or cholangiocarcinoma. This study describes the histolopathology and changes in gene expression in the rat liver during short-term feeding of FB1. Male Fischer rats were fed either FB1 250 mg/kg or control diet, and were killed weekly for 5 weeks. FB1 caused a predominantly zone 3 'toxic' liver injury, with hepatocyte death due to necrosis and apoptosis. Hepatocyte injury and death were mirrored by hepatic stellate cell proliferation and marked fibrosis, with progressive disturbance of architecture and formation of regenerative nodules. Despite ongoing hepatocyte mitotic activity, oval cell proliferation was noted from week 2, glutathione S-transferase pi-positive hepatic foci and nodules developed and, at later time points, oval cells were noted inside some of the 'atypical' nodules. Northern blot (mRNA) analysis of liver specimens from weeks 3 to 5 showed a progressive increase in gene expression for alpha-fetoprotein, hepatocyte growth factor, transforming growth factor alpha (TGF-alpha) and especially TGF-beta1 and c-myc. Immunostaining with LC(1-30) antibody demonstrated a progressive increase in expression of mature TGF-beta1 protein by hepatocytes over the 5 week feeding period. The overexpression of TGF-beta1 may be causally related to the prominent apoptosis and fibrosis seen with FB1-induced liver injury. Increased expression of c-myc may be involved in the cancer promoting effects of FB1.

Chronic ulcerative colitis may be accompanied by a variety of epithelial changes, including loss of goblet cells, Paneth cell metaplasia, villous metaplasia, and dysplasia. Total colitis is also accompanied by an increased incidence of adenocarcinoma. All these changes are assumed to be secondary to repeated mucosal damage, but how they develop is unknown. Little attention has been paid to the enteroendocrine cell population, despite the postulated role of these cells as producers of trophic hormones. We describe two patients with long-standing ulcerative colitis who developed both adenocarcinoma and carcinoid tumours. In both, there were increased numbers of enteroendocrine cells in the uninvolved colonic mucosa. We suggest that an increased enteroendocrine cell mass may be part of a non-specific reaction to chronic mucosal injury, and by producing an elevated level of trophic hormones may act as a promoter in the development of neoplasia.

The paper describes the changes in the cricopharyngeal muscle in seven cases of dysphagia resulting from obstruction at this level which was relieved by myotomy. Histological features included degeneration and regeneration in the muscle fibres with interstitial fibrosis which was severe in some of the cases. It is considered that this restrictive fibrosis is the cause of the dysphagia and that it is secondary to muscle fibre damage, the cause of which is at present obscure. Minor degrees of muscle damage and regeneration were seen rarely in controls and fibrosis was never present. There was no evidence of underlying vascular or neurological disease in six cases; the seventh had a previous history of scleroderma but this was not thought to be the cause of the cricopharyngeal lesion. The age incidence ranged from 1 to 5 years at the onset of dysphagia; in six of the seven it was 50 years or more.

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