The scientific basis for evaluation and management of thrombotic disorders.

The hemostatic mechanisms at work in the body involve a complex series of interactions between platelets, the endothelium, and the coagulation cascade. Much has been learned regarding the molecular mechanisms governing these intricate processes. The hypercoagulable state involves a disruption of the normal homeostatic equilibrium. This state may be either inherent or acquired. The prevention of associated thromboembolic complications requires therapeutic anticoagulation. A broader understanding of the factors contributing to these prothrombotic tendencies and the subtleties involved in their management provides the surgeon with another weapon in the armamentarium to promote better and safer patient outcomes.

Characterization of HPV16 L1 loop domains in the formation of a type-specific, conformational epitope.

BACKGROUND: Virus-like particles (VLPs) formed by the human papillomavirus (HPV) L1 capsid protein are currently being tested in clinical trials as prophylactic vaccines against genital warts and cervical cancer. The efficacy of these vaccines is critically dependent upon L1 type-specific conformational epitopes. To investigate the molecular determinants of the HPV16 L1 conformational epitope recognized by monoclonal antibody 16A, we utilized a domain-swapping approach to generate a series of L1 proteins composed of a canine oral papillomavirus (COPV) L1 backbone containing different regions of HPV16 L1. RESULTS: Gross domain swaps, which did not alter the ability of L1 to assemble into VLPs, demonstrated that the L1 N-terminus encodes at least a component of the 16A antigenic determinant. Finer epitope mapping, using GST-L1 fusion proteins, mapped the 16A epitope to the L1 variable regions I and possibly II within the N-terminus. CONCLUSIONS: These results suggest that non-contiguous loop regions of L1 display critical components of a type-specific, conformational epitope.