We conducted a two-stage genome-wide association study (GWAS) of pancreatic cancer, a cancer with one of the poorest survival rates worldwide. Initially, we genotyped 558,542 single nucleotide polymorphisms in 1,896 incident cases and 1,939 controls drawn from twelve prospective cohorts plus one hospital-based case-control study. In a combined analysis adjusted for study, sex, ancestry and five principal components that included an additional 2,457 cases and 2,654 controls from eight case-control studies, we identified an association between a locus on 9q34 and pancreatic cancer marked by the single nucleotide polymorphism, rs505922 (combined P=5.37 × 10-8; multiplicative per-allele odds ratio (OR) 1.20; 95% CI 1.12-1.28). This SNP maps to the first intron of the ABO blood group gene. Our results are consistent with earlier epidemiologic evidence suggesting that people with blood group O may have a lower risk of pancreatic cancer than those with groups A or B.

The membraneand ribonucleocapsid (RNP)-binding domains of the matrix (Ml) protein of influenza A virus (WSN strain) were partially mapped and characterized by reactivity with monoclonal antibodies (MAb) as well as by proteolytic cleavages and amino acid sequencing of the resulting peptides. Of two peptides formed by formic acid hydrolysis, a 9-kilodalton fragment at the amino-terminal third of the Ml protein was recognized by MAb M2-1C6 (to epitope 1), and a 15-kilodalton fragment at the carboxy-terminal two-thirds was recognized by MAb 289/4 (to epitope 2). Partial cleavage by staphylococcal V8 protease gave rise to a 16-kilodalton peptide, mapping to amino acid 8, which was recognized by MAbs to all three epitopes but rather weakly by MAb 904/6 to epitope 3. These studies suggest that epitope 1 of the Ml protein resides between amino acids 8 and 89, whereas epitopes 2 and possibly 3 are located between amino acids 89 and 141 or somewhat more carboxy distal. The intact Ml protein and its N-terminal 9-and 10-kilodalton peptides generated by formic acid or V8 protease cleavage, respectively, reconstituted with dipalmitoylphosphatidylcholine vesicles, but these N-terminal peptides had little effect on in vitro transcription of the RNP core. In sharp contrast, both intact Ml protein and the C-terminal 15-kilodalton formic acid fragment were able to inhibit viral transcription markedly. Moreover, MAb 289/4 (to epitope 2) reversed this inhibited transcription significantly. These studies suggest that the lipid-binding domain of the Ml protein is located within the amino-terminal third, whereas the site involved in the interaction of the Ml protein with RNP cores is located within the carboxy-terminal

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Cell culture is now available as a method for the production of influenza vaccines in addition to eggs. In accordance with currently accepted practice, viruses recommended as candidates for vaccine manufacture are isolated and propagated exclusively in hens' eggs prior to distribution to manufacturers. Candidate vaccine viruses isolated in cell culture are not available to support vaccine manufacturing in mammalian cell bioreactors so egg-derived viruses have to be used. Recently influenza A (H3N2) viruses have been difficult to isolate directly in eggs. As mitigation against this difficulty, and the possibility of no suitable egg-isolated candidate viruses being available, it is proposed to consider using mammalian cell lines for primary isolation of influenza viruses as candidates for vaccine production in egg and cell platforms.To investigate this possibility, we tested the antigenic stability of viruses isolated and propagated in cell lines qualified for influenza vaccine manufacture and subsequently investigated antigen yields of such viruses in these cell lines at pilot-scale. Twenty influenza A and B-positive, original clinical specimens were inoculated in three MDCK cell lines. The antigenicity of recovered viruses was tested by hemagglutination inhibition using ferret sera against contemporary vaccine viruses and the amino acid sequences of the hemagglutinin and neuraminidase were determined. MDCK cell lines proved to be highly sensitive for virus isolation. Compared to the virus sequenced from the original specimen, viruses passaged three times in the MDCK lines showed up to 2 amino acid changes in the hemagglutinin. Antigenic stability was also established by hemagglutination inhibition titers comparable to those of the corresponding reference virus. Viruses isolated in any of the three MDCK lines grew reasonably well but variably in three MDCK cells and in VERO cells at pilot-scale. These results indicate that influenza viruses isolated in vaccine certified cell lines may well qualify for use in vaccine production.