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Background: We describe the serological response following H1N1-2009 influenza A infections confirmed by reversetranscriptase polymerase chain reaction (RT-PCR). Methodology and Principal Findings: The study included patients admitted to hospital, subjects of a seroepidemiologic cohort study, and participants identified from outbreak studies in Singapore. Baseline (first available blood sample) and follow-up blood samples were analyzed for antibody titers to H1N1-2009 and recently circulating seasonal influenza A virus strains by hemagglutination inhibition (HI) and virus micro-neutralization (VM) assays. 267 samples from 118 cases of H1N1- 2009 were analyzed. Geometric mean titers by HI peaked at 123 (95% confidence interval, CI 43-356) between days 30 to 39. The chance of observing seroconversion (four-fold or greater increase of antibodies) was maximized when restricting analysis to 45 participants with baseline sera collected within 5 days of onset and follow-up sera collected 15 or more days after onset; for these participants, 82% and 89% seroconverted to A/California/7/2009 H1N1 by HI and VM respectively. A four-fold or greater increase in cross-reactive antibody titers to seasonal A/Brisbane/59/2007 H1N1, A/Brisbane/10/2007 H3N2 and A/Wisconsin/15/2009 H3N2 occurred in 20%, 18% and 16% of participants respectively. Conclusions and Significance: Appropriately timed paired serology detects 80-90% RT-PCR confirmed H1N1-2009; Antibodies from infection with H1N1-2009 cross-reacted with seasonal influenza viruses. [ABSTRACT FROM AUTHOR]

We previously reported that messenger RNA expression of DENN (differentially expressed in normal and neoplastic cells) is considerably higher in cancer cell lines than in normal cells. In our present study, we established that certain cancer cell lines express conspicuously higher levels of the 2 DENN isoforms in contrast to the 2 pro-apoptotic IG20 isoforms. Antisense DENN oligodeoxynucleotide treatment of K36 cells in vitro induced extensive apoptosis, while antisense DENN silencing of K36 tumor-bearing mice caused significant tumor regression in vivo. Compared to wild-type murine embryonic fibroblasts, antisense treatment of NFκB and TNFR1 KO cells resulted in markedly more pronounced cell death, whereas antisense-treated TNFα and TNFR2 knockouts exhibited less prominent apoptosis. Cell viability and apoptosis were authenticated by flow cytometry, membrane integrity, TUNEL, annexin V assays, histology and electron microscopy. Antisense abrogation of DENN expression culminated in upregulated expression of TNFR2, TRAIL and Fas, but downregulation of TNFα, TNFR1 and cyclin D3. Conversely, DENN overexpression stimulated cell proliferation and led to upregulated TRPM2 and cyclin B1, but diminished expression of Fas, TNFR2, TRAIL and Egr-1. The participation of TNFα, TNFR1, TNFR2 and Fas in the inhibition of DENN expression was also demonstrated. These data support the anti-apoptotic and cell survival role of DENN, especially in malignant cells, and its interaction with specific genes and proteins involved in the apoptotic and cell cycle pathways. © 2003 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]