A novel cobra venom metalloproteinase, mocarhagin, cleaves a 10-amino acid peptide from the mature N terminus of P-selectin glycoprotein ligand receptor, PSGL-1, and abolishes P-selectin binding.

Initial rolling of circulating neutrophils on a blood vessel wall prior to adhesion and transmigration to damaged tissue is dependent upon P-selectin expressed on endothelial cells and its specific neutrophil receptor, the P-selectin glycoprotein ligand-1 (PSGL-1). Pretreatment of neutrophils, HL60 cells, or a recombinant fucosylated soluble form of PSGL-1 (sPSGL-1.T7) with the cobra venom metalloproteinase, mocarhagin, completely abolished binding to purified P-selectin in a time-dependent and EDTA- and diisopropyl fluorophosphate-inhibitable manner consistent with mocarhagin selectively cleaving PSGL-1. A polyclonal antibody against the N-terminal peptide Gln-1-Glu-15 of mature PSGL-1 immunoprecipitated sPSGL-1.T7 but not sPSGL-1.T7 treated with mocarhagin, indicating that the mocarhagin cleavage site was near the N terminus. A single mocarhagin cleavage site between Tyr-10 and Asp-11 of mature PSGL-1 was determined by N-terminal sequencing of mocarhagin fragments of sPSGL-1.T7 and is within a highly negatively charged amino acid sequence 1-QATEYEYLDY decreases DFLPETEPPE, containing three tyrosine residues that are consensus sulfation sites. Consistent with a functional role of this region of PSGL-1 in binding P-selectin, an affinity-purified polyclonal antibody against residues Gln-1-Glu-15 of PSGL-1 strongly inhibited P-selectin binding to neutrophils, whereas an antibody against residues Asp-9-Arg-23 was noninhibitory. These combined data strongly suggest that the N-terminal anionic/sulfated tyrosine motif of PSGL-1 as well as downstream sialylated carbohydrate is essential for binding of P-selectin by neutrophils.

Halo external fixation of nasal fractures.

The halo, long in medical use for cervical traction, subsequently has been adapted as a method of external fixation for severe facial fractures. We have recently used a light-weight halo in four patients with severe mid-facial fractures and crushed nasal skeletons. External traction proved to be superior to any method we have previously used to support the repositioned nasal bones. We strongly recommend external traction for severe nasal fractures in which other methods may not give a complete and stable bony reduction.

Osteomyelitis of the mandibular condyle secondary to dental extractions.

Although osteomyelitis of the mandibular condyle secondary to dental extraction is scarcely mentioned in the medical and dental literature, we have seen three cases within a two-year period. The first two patients were examined for an eroded condyle three months and 18 months following the extractions. The third patient, who was treated one month after extraction for acute osteomyelitis of the condyle, has done well. All three patients required operations and administration of long-term antibiotics.