In 1000 primary gastric carcinomas, 70 (7.0%) contained Epstein-Barr virus (EBV) genomic sequences detected by PCR and Southern blots. The positive tumors comprised 8 of 9 (89%) undifferentiated lymphoepithelioma-like carcinomas, 27 of 476 (5.7%) poorly differentiated adenocarcinomas, and 35 of 515 (6.8%) moderately to well-differentiated adenocarcinomas. In situ EBV-encoded small RNA 1 hybridization and hematoxylin/eosin staining in adjacent sections showed that the EBV was present in every carcinoma cell but was not significantly present in lymphoid stroma and in normal mucosa. Two-color immunofuorescence and hematoxylin/eosin staining in parallel sections revealed that every keratin-positive epithelial maiant cell expressed EBV-determined nuclear antigen 1 (EBNA1) but did not significantly express CD45+ infiltrating leukocytes. A single fused terminal fragment was detected in each of the EBNA1-expressing tumors, thereby suggesting that the EBV-carrying gastric carcinomas represent clonal proliferation of cells infected with EBV. The carcinoma cells had exclusively EBNA1 but not EBNA2, -3A, -3B, and -3C; leader protein; and latent membrane protein 1 because of methylation. The patients with EBV-carrying gastric carcinoma had elevated serum EBVspecific antibodies. The EBV-specific cellular immunity was not signficantly reduced; however, the cytotoxic T-cell target antigens were not expressed. These findings strongly suggest a causal relation between a significant proportion of gastric carcinoma and EBV, and the virus-carrying carcinoma cells may evade immune surveillance.

Epstein-Barr virus (EBV), a ubiquitous human herpesvirus and an aetiological agent of infectious mononucleosis, has a unique tropism for B lymphocytes. Clinical and laboratory features of chronic active EBV infections are chronic or persistent infectious mononucleosis-like symptoms and high antibody titre against early antigens (EA). Kawasaki disease (KD), aetiology unknown, is thought to be self-limited immunologically mediated vasculitis. Clinical features of KD are fever, rash, mucositis, lymphadenopathy and coronary artery damage. We report here a child with chronic active EBV infection accompanied by dilatation of coronary arteries. All the EBV-determined nuclear antigen (EBNA)-positive lymphocytes had exclusively CD4 antigen, as revealed by dual staining immunofluorescence analysis. Southern blot hybridization showed that the purified CD4+ cells harboured EBV genome.

Summary Although case-oriented evidence for an association of Epstein-Barr virus (EBV) with

The expression of the protooncogenes ETSI and ETS2 has been studied in purifled human T cells activated either by cross-linking of the T-cell receptor-CD3 complex on their cell surface or by direct stimulation with phorbol esters and ionomycin. Our results show that resting T cells express high levels of ETS1 mRNA and protein, while expression of ETS2 is undetectable. Upon T-cell activation, ETS2 mRNA and proteins are induced, while ETSI gene expression decreases to very low levels. Late after stimulation, ETS1 mRNA is reinduced and maintained at a high level, while ETS2 gene expression decreases to undetectable levels. Therefore, it appears that in human T cells, ETS2 gene products are associated with cellular activation and proliferation, while ETSI gene products are preferentially expressed in a quliescent state.The cellular c-ets family ofgenes have been identified by their sequence similarities with the viral v-ets oncogene of the E26 avian leukemia virus (1, 2). The c-ets-1 (3-5), c-ets-2 (3, 4), c-erg (6, 7), c-elk-i, and c-elk-2 genes (8) are members of the c-ets family ofgenes. In humans, ETSI and ETS2 are localized on different chromosomes (9) and code for distinct sets of mRNA (3, 5) and proteins (10-12). ETSJ and ETS2 code for structurally related proteins (70%o similarity) (4) that are primarily localized in the nucleus (10, 13) and are capable of binding to DNA (13). The DNA-binding domain has been localized to the carboxyl terminus ofETS1 (14), a region highly conserved among all ETS family members (4). Both ETS1 and ETS2 proteins are labile nuclear phosphoproteins (10,12,15). They share many properties with other nuclear oncogene products like JUN, FOS, and MYC: nuclear localization, rapid turnover, and quick response to second messengers, suggesting that the c-ets gene products may also play a vital role during cell growth. In fact, the gene transfection and subsequent overexpression ofmurine Ets-2 has recently been shown to abolish the serum requirement for cell growth and stimulate the proliferation of NIH 3T3 fibroblasts (16).Although c-ets-1 mRNA is detectable in different murine (17-19) and human tissues (20, 21), c-ets-1 mRNA and proteins are expressed at high levels in the thymus. Thymus is the major site for T-cell development, differentiation, and functional maturation. Initially, the thymus is populated by CD4-CD8-(DN, double negative) cells, some of which will differentiate into CD4+ CD8+ (DP, double positive) cells.The single-positive CD4+ CD8-or CD4-CD8+ thymocytes emerge later and subsequently migrate from the thymus into peripheral lymphoid sites (22). We have shown that: (i) the murine Ets-2 expression appears 1 day earlier than Ets-J expression, corresponding to both DN and DP blast thymocytes; (ii) the Ets-1 expression begins in 18-day-old fetal thymocytes, coinciding with the appearance of singlepositive thymocytes; (iii) both Ets-J and Ets-2 genes are selectively expressed in CD4+ CD8-thymocytes rather than in DN or CD8+ CD4-subsets; (iv) both Ets-l and Ets-2 expressi...