Replication and pathogenesis of avian influenza A (H5N1) virus infection in polarised human bronchial and alveolar epithelium.

1. In vitro models of polarised human respiratory epithelial cells were established to investigate the tropism and innate host responses of influenza A (H5N1 and H1N1) viruses. 2. Both viruses efficiently infected alveolar epithelial cells of both the apical and basolateral surfaces of the epithelium, whereas release of newly formed virus was mainly from the apical surface of the epithelium. 3. H5N1 virus was a more potent inducer of cytokines and chemokines in alveolar epithelial cells than H1N1 virus. Such chemokines were secreted onto both the apical and basolateral surfaces of the polarised alveolar epithelium. 4. In bronchial epithelium, the H5N1 virus replicated more efficiently and induced a stronger type I interferon response in the undifferentiated NHBE cells than did H1N1 virus. In contrast, in well-differentiated cultures, H5N1 virus replication was less efficient and elicited a lower interferon-beta response than did H1N1 virus. 5. Recombinant virus with vRNPs of a mammalian PB2 and an avian PB1 had the strongest polymerase activities, and replicated better in human cell cultures, especially at a high incubation temperature. These viruses were potent inducers of cytokines and chemokines in primary human alveolar epithelial cells.

Comparative genomic hybridization: comparison between esophageal squamous cell carcinoma and gastric cardia adenocarcinoma from a high-incidence area for both cancers in Henan, northern China.

Esophageal squamous cell carcinoma (SCC) remains the leading cause of cancer related deaths in Linzhou (formerly Linxian), the highest incidence area for esophageal cancer (EC) in Henan, northern China. In China, gastric cardia adenocarcinoma (GCA) shares very similar geographic distribution with SCC, suggesting the possibility of similar risk factors involved in SCC and GCA carcinogenesis in these areas. However, the underlying genetic alterations for esophageal and gastric cardia carcinogenesis, especially for the molecular difference between SCC and GCA, are largely unknown. The present study was thus undertaken to determine the difference in chromosomal aberrations in SCC (n = 37) and GCA (n = 31) using the comparative genomic hybridization method (CGH). All the patients were from Linzhou, Henan, a high-risk geographic region for both SCC and GCA. CGH results showed that chromosomal aberrations with different degrees were identified both in SCC and GCA. In SCC, chromosomal profile of DNA copy number was characterized by most frequently detected gains at 8q (29/37, 78%), 3q (24/37, 65%) and 5p (19/37, 51%); and frequently detected losses at 3p (21/37, 57%), 8p and 9q (14/37, 38%). In GCA, the frequently detected gains were identified at 20q (13/31, 42%), 6q (12/31, 39%) and 8q (11/31, 35%); the DNA copy number losses in GCA occurred frequently at 17p (17/31, 55%), 19p (15/31, 48%) and 1p (14/31, 45%). Statistically, there were evident differences between SCC and GCA in DNA copy number gains at 8q, 3q, 5p and 20q (P < 0.05) and in losses at 3p, 8p, 5q, 17p and 18q (P < 0.05). Gains at 8q were frequently observed in both SCC and GCA. Gains at 3q and 8p were frequently observed in TNM stage III of both SCC and GCA. The present CGH results provide candidate regions that may contain specific related genes involved in SCC and GCA in the Linzhou population. Gains at 8q, 3q and 5p and losses at 3p, 8p and 9q were specifically implicated in SCC; gains at 20q, 6q and 8q and losses at 17p, 19p and 1p were specifically implicated in GCA; gains at 8q were implicated in both SCC and GCA.