Intracellular growth of Listeria monocytogenes begins after lysis of the primary vacuole formed upon bacterial entry into a host cell. Listeriolysin O (LLO), a pore-forming hemolysin encoded by hly, is essential for vacuolar lysis in most cell types. However, in human epithelial cells, LLO ؊ mutants are capable of growth, suggesting that gene products other than LLO are capable of mediating escape from a vacuole. In this study, we investigated the role of other bacterial gene products in lysis of the primary vacuole in the human epithelial cell line Henle 407. Double internal in-frame deletion mutants were constructed by introducing a mutated hly allele into strains harboring deletions in either of the phospholipase C (PLC)-encoding genes or a metalloprotease-encoding gene. Bacterial escape from the primary vacuole, intracellular growth, and cell-to-cell spread were evaluated in Henle 407 cells. The results indicated that, in the absence of LLO, the broad-range PLC and the metalloprotease were both required for lysis of the primary vacuole in Henle 407 cells. Although phosphatidylinositol-specific PLC was not required, the efficiency of escape was reduced in an LLO phosphatidylinositol-specific PLC double mutant. These observations suggest that the relative importance of LLO, the phospholipases, and the metalloprotease may vary in different cell types or in cells from different species. In addition, these studies provide insight into the mechanisms of action of virulence determinants involved in the lysis of vacuolar membranes.

No abstract

Aims: To compare the safety and efficacy of 2 anti-vascular-endothelial-growth-factor agents – bevacizumab (Avastin) versus ranibizumab (Lucentis) – in the treatment of patients with neovascular age-related macular degeneration (AMD). Methods: Retrospective analysis of patients who received intravitreal injections of bevacizumab or ranibizumab for neovascular AMD. Primary outcome measures were best-corrected visual acuity (BCVA) and central foveal thickness (CFT) assessed by Spectral Domain scanning laser ophthalmoscope-optical coherence tomography (SD-OCT). A secondary outcome measure was the report of any adverse events in the 2 groups. Results: The number of injections in the bevacizumab group was 184 (average of 4.7 per eye) compared to 187 in the ranibizumab group (average of 5.5 per eye). The mean logMAR equivalent of BCVA at 1 month after the injection improved by 0.18 in the bevacizumab group (p = 0.009) and by 0.13 in the ranibizumab group (p = 0.004). The average SD-OCT CFT decreased from 325 ± 72 to 300 ± 69 μm in the bevacizumab group (p = 0.016) and from 307 ± 57 to 289 ± 56 μm in the ranibizumab group (p = 0.017). In the bevacizumab group, there was 1 event of lower extremity pain (0.54%) and 1 event of increased arterial blood pressure (0.54%). In the ranibizumab group, there were 2 events of transiently increased intraocular pressure (1.1%) and 1 event (0.53%) of intraocular inflammation following injection. Conclusions: Bevacizumab and ranibizumab treatments resulted in similar gains in visual acuity and reduction in macular thickness, documented each month following injection. Intravitreal bevacizumab appears to be as safe and effective as intravitreal ranibizumab in the treatment of exudative AMD.

No abstract