|Laboratory-based assessment of influenza in German ambulant patients from 1998 to 2008. |
Terletskaia-Ladwig E, Eggers M, Meier S, Leinmuller M, Schneider F, Schmid M, Enders M
BACKGROUND: : In Germany, the cost for PCR diagnosis of influenza in ambulant patients was not covered by the national statutory health insurance system until 2008. Therefore, cell culture was the standard method applied for routine diagnosis. We have prospectively compared a 1-day rapid cell culture assay (RCA) with conventional cell culture (CCC) during the influenza seasons from 1997/1998 to 2007/2008 and with real-time PCR analysis during the influenza seasons 2003/2004 and 2006/2007. PATIENTS AND METHODS: : This study is based on 4,262 respiratory samples obtained from ambulant patients between January 1998 and May 2008. The RCA was performed in microtiter plates that were stained with monoclonal antibodies to influenza virus A and B 16 h after inoculation. RESULTS: : A total of 1,221 specimens were found to be positive by the cell culture methods - 1,143 (93.6%) by the RCA and 1,012 (82.9%) by the CCC. The sensitivity of the RCA and CCC versus PCR was 75.4% (221/293) and 58% (170/293), respectively. The specificity of both cell culture assays versus PCR was 100%. Influenza A represented 79.3% of the cases diagnosed. An increased activity of influenza was observed between January and March, with the rate of influenza-positive cases being highest for kindergarten and school-aged children. CONCLUSION: : While PCR is the most sensitive assay for the diagnosis of influenza, the RCA can still be used for diagnosis and surveillance of this disease. Based on our findings and given the known fact that influenza antibodies reach a plateau 2-4 weeks after immunization, the optimal time for vaccination in Germany is from October through November. Kindergarten and school-aged children represent an important reservoir of infection. Consequently, routine immunization should be considered for this age group to prevent the spread of influenza.
|Matrix metalloproteinase-2 regulates vascular patterning and growth affecting tumor cell survival and invasion in GBM. |
Rose Du,Claudia Petritsch,Kan Lu,Patty Liu,Anna Haller,Ruth Ganss,Hanqiu Song,Scott Vandenberg,Gabriele Bergers
Glioblastoma multiforme (GBM) is one the most aggressive brain tumors due to the fast and invasive growth that is partly supported by the presence of extensive neovascularization. The matrix metalloproteinase MMP-2 has been associated with invasive and angiogenic properties in gliomas and is a marker of poor prognosis. Since MMP-2 is expressed in both tumor cells and endothelial cells in GBM, we generated genetically engineered MMP-2 knockout (MMP-2ko) GBM to examine the importance of the spatial expression of MMP-2 in tumor and/or normal host-derived cells. MMP-2-dependent effects appeared to be dose-dependent irrespective of its expression pattern. GBM completely devoid of MMP-2 exhibited markedly increased vascular density associated with vascular endothelial growth factor receptor 2 (VEGFR2) activation and enhanced vascular branching and sprouting. Surprisingly, despite the high vascular density, tumor cells were more prone to apoptosis, which led to prolonged survival of tumor-bearing mice, suggesting that the increased vascularity is not functional. Congruently, tumor vessels were poorly perfused, exhibited lower levels of VEGFR2, and did not undergo proper maturation because pericytes of MMP-2ko tumors were not activated and were less abundant. As a result of impaired and dysfunctional angiogenesis, MMP-2ko GBM became more invasive, predominantly by migrating along blood vessels into the brain parenchyma.기사 전문