Osteopontin (OPN) is a secreted phosphoprotein involved in cellular proliferation and associated with tumor progression. Although an intracellular form of OPN has been described, its function remains unknown. In this study, a novel nuclear location for intracellular OPN and a correlation with cell division were demonstrated. OPN distinctly localized to the nucleus in a subset of transiently transfected human embryonic kidney 293 cells. Immunoblotting confirmed the nuclear location of native OPN, and results from immunofluorescence studies suggested an association between nuclear OPN and cell cycle progression. Flow cytometry revealed that nuclear and cellular OPN content rose significantly during the S and G(2)/M phases, respectively. Treatment of cells with the DNA polymerase inhibitor aphidicolin prevented cell cycling and greatly reduced cellular OPN content. The intracellular location of OPN coincided with polo-like kinase-1 (Plk-1), a member of the polo-like kinase family, which, in part through their regulation of centrosome-related events, are integral to successful cellular mitosis. OPN and Plk-1 were coimmunoprecipitated from nuclear, but not cystoslic, extracts, demonstrating an interaction that is limited to the nucleus, presumably during mitosis. Deletion of the COOH terminus of OPN militated against nuclear localization and Plk-1 interaction. Elevated expression of OPN was also associated with an increase in the number of multinucleate 293 cells, whereas transfection of the COOH-terminal-deleted OPN decreased the percentage of multinucleate cells below basal levels. These findings implicate intranuclear OPN as a participant in the process of cell duplication.
Bacillus Calmette-Guérin (BCG) is a live attenuated strain of Mycobacterium bovis that has proven effective in the treatment of early-stage bladder cancer. Although intravesical therapy with BCG is generally considered safe, serious complications including hematuria, granulomatous pneumonitis, hepatitis, and life-threatening BCG sepsis are well known. BCG-related vascular infections are rarely reported. We present a case of a ruptured abdominal aortic aneurysm secondary to M bovis infection 2 years after intravesical instillation of BCG and review the related literature.
Over the last several years, treatment modalities have changed for infected aortic aneurysms. Surgical treatment has undergone a paradigm shift from débridement and extra-anatomic bypass to direct reconstruction to, most recently, endovascular repair. Although many reports of endovascular repair of such aneurysms are favorable, the following two cases highlight some of the concerns with endografts in an infected field. Specifically, we urge caution when considering endovascular repair of Salmonella-infected arterial pathologies.
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