Regulation of P-selectin binding to the neutrophil P-selectin counter-receptor P-selectin glycoprotein ligand-1 by neutrophil elastase and cathepsin G

In the inflammatory response, leukocyte rolling before adhesion and transmigration through the blood vessel wall is mediated by specific cell surface adhesion receptors. Neutrophil rolling involves the interaction of P-selectin expressed on activated endothelium and its counter-receptor on neutrophils, P-selectin glycoprotein ligand-1 (PSGL-1). Here, it is reported that P-selectin binding to neutrophils is lost under conditions that cause the release of proteinases from neutrophil primary granules. Treatment of neutrophils with the purified neutrophil granule proteinases, cathepsin G and elastase, rapidly abolished their capacity to bind P-selectin. This inactivation corresponded to loss of the N-terminal domain of PSGL-1, as assessed by Western blot analysis. A loss of intact PSGL-1 protein from the surfaces of neutrophils after the induction of degranulation was also detected by Western blot analysis. Cathepsin G initially cleaved near the PSGL-1 N-terminus, whereas neutrophil elastase predominantly cleaved at a more C-terminal site within the protein mucin core. Consistent with this, cathepsin G cleaved a synthetic peptide based on the PSGL-1 N-terminus between Tyr-7/Leu-8. Under conditions producing neutrophil degranulation in incubations containing mixtures of platelets and neutrophils, the loss of PSGL-1, but not P-selectin, from platelet-neutrophil lysates was detected. Cathepsin G- or neutrophil elastase-mediated PSGL-1 proteolysis may constitute a potential autocrine mechanism for down-regulation of neutrophil adhesion to P-selectin.     

Elbow ligament strain under valgus load: a biomechanical study.

This study assessed the importance of the anterior and posterior bundles of the medial collateral ligament in the elbow by measuring in situ strain in response to valgus loads at three positions of forearm rotation throughout a full arc of motion. Strain in the anterior bundle was significantly greater than in the posterior bundle and increased with more flexion. The anterior bundle developed strain at a lower flexion angle (30 degrees) than the posterior bundle (60 degrees). Strain ratio increased with load increase for all flexion angles. Forearm position minimally affected strain. These results indicate that the anterior bundle is important in resisting a valgus load, particularly in mid-flexion, while the importance of the posterior bundle increases as the elbow approaches full flexion.     

Recurrence of progressive multifocal leukoencephalopathy despite immune recovery in two HIV seropositive individuals

We present two cases of recurrent progressive multifocal leukoencephalopathy (PML) in patients with long standing virally suppressed human immunodeficiency virus (HIV) and normal CD4+ T cell count who were taking stable regimens of highly active antiretroviral therapy (HAART). This has significant implications for other patients with a past history of PML, not just those with HIV but also those on medications such as natalizumab or fumarates.     

前后路联合手术治疗髋臼双柱骨折疗效分析

目的:探讨前后路联合手术治疗髋臼双柱骨折的效果并分析影响疗效的相关因素。方法:2007年8月至2009年7月收治髋臼双柱骨折患者19例,男13例,女6例;年龄27～52岁,平均39.6岁。高位双柱骨折11例,低位双柱骨折8例,双柱骨折累及骶髂关节1例。受伤至手术时间4～11 d,平均5.8 d。患者均采用前后联合入路手术,重建钢板和螺钉内固定。结果:除1例死亡外本组全部获随访,随访时间12～18个月,平均13.6个月。关节功能根据Harris评分标准,术后功能优9例,良7例,可2例。结论:经前后路联合切开复位内固定治疗髋臼双柱骨折疗效满意。