Search

The pathogenetic role of interferon-gamma (IFN-gamma) in acute graft-versus-host disease (GVHD) was examined in a murine model. IFN-gamma gene expression was evaluated by northern blotting and mRNA in situ hybridization. The temporal and tissue specific patterns of IFN-gamma gene expression were related to the patterns of major histocompatibility complex (MHC) antigen induction and of tissue injury. Markedly increased levels of IFN-gamma transcripts were seen in the spleen during the early lymphoproliferative phase and coincided with widespread MHC induction in non-lymphoid tissues. Increased IFN-gamma transcripts were also found in the non-lymphoid target tissues during the phase of subsequent tissue injury. These findings support a role for IFN-gamma in leading to widespread MHC induction during acute GVHD and suggest that IFN-gamma may also contribute to target tissue injury during acute GVHD., (Copyright 1999 John Wiley & Sons, Ltd.)

Abnormalities in the p53 tumour suppressor gene and in the expression of its protein are common in colorectal carcinoma. The prognostic significance of these p53 abnormalities was studied in 66 patients with colorectal cancer, followed for more than 10 years. Single-strand conformation polymorphism (SSCP) analysis was used to detect alterations in exons 5-8 of the p53 gene. Paraffin sections were examined immunohistochemically for p53 overexpression with the monoclonal antibody DO-7 (Dako) both with and without microwave antigen retrieval. Abnormalities of the p53 gene were found in 41 per cent of cases by SSCP analysis. Outcome was unrelated to SSCP abnormalities (P = 0.19), except for the Dukes' A and B subgroup, where decreased survival was found in cases with abnormal SSCP (P = 0.01). Overexpression of p53 protein was seen by immunohistochemistry in 47 per cent of cases without, and in 52 per cent of cases with microwave antigen retrieval. Immunohistochemical overexpression of p53 protein either with or without microwave antigen retrieval was an independent prognostic indicator of poor survival. These results suggest that for routine purposes, immunohistochemical detection of the p53 protein product may be more useful than SSCP analysis of the encoding p53 gene in identifying those at high risk of colorectal cancer recurrence and death.