Characterization of human platelet binding of recombinant T cell receptor ligand

<p>Abstract</p> <p>Background</p> <p>Recombinant T cell receptor ligands (RTLs) are bio-engineered molecules that may serve as novel therapeutic agents for the treatment of neuroinflammatory conditions such as multiple sclerosis (MS). RTLs contain membrane distal α1 plus β1 domains of class II major histocompatibility complex linked covalently to specific peptides that can be used to regulate T cell responses and inhibit experimental autoimmune encephalomyelitis (EAE). The mechanisms by which RTLs impede local recruitment and retention of inflammatory cells in the CNS, however, are not completely understood.</p> <p>Methods</p> <p>We have recently shown that RTLs bind strongly to B cells, macrophages, and dendritic cells, but not to T cells, in an antigenic-independent manner, raising the question whether peripheral blood cells express a distinct RTL-receptor. Our study was designed to characterize the molecular mechanisms by which RTLs bind human blood platelets, and the ability of RTL to modulate platelet function.</p> <p>Results</p> <p>Our data demonstrate that human blood platelets support binding of RTL. Immobilized RTL initiated platelet intracellular calcium mobilization and lamellipodia formation through a pathway dependent upon Src and PI3 kinases signaling. The presence of RTL in solution reduced platelet aggregation by collagen, while treatment of whole blood with RTL prolonged occlusive thrombus formation on collagen.</p> <p>Conclusions</p> <p>Platelets, well-known regulators of hemostasis and thrombosis, have been implicated in playing a major role in inflammation and immunity. This study provides the first evidence that blood platelets express a functional RTL-receptor with a putative role in modulating pathways of neuroinflammation.</p

Cocaine-Induced Giant Bullous Emphysema

Background. Emphysematous bullae, defined as airspaces of greater than or equal to one centimeter in diameter, have a variety of etiologies such as tobacco use and alpha-1 antitrypsin being the most common. Emphysematous bullae have also been reported in patients using cocaine usually involving the lung periphery and sparing the central lung parenchyma. We present a case of a male with a history of cocaine abuse found to have a singular giant emphysematous bulla occupying >95% of the right hemithorax requiring video-assisted thoracic surgery (VATS) with a favorable outcome. Case Presentation. A 50-year-old male with a history of chronic cocaine abuse was found unresponsive in the field and given multiple doses of naloxone without any improvement in mental status. On presentation to the emergency department, chest X-ray as well as CT scan of the chest were performed which were suggestive of an extensive pneumothorax of the right lung requiring placement of a chest tube. The patient was subsequently intubated and underwent bronchoscopy with right chest VATS which found a giant bulla encasing the entire right pleural cavity. During the procedure, he underwent resection of the bullae and a partial right pleurodesis. After the procedure, patient’s respiratory status significantly improved, and he was discharged in a stable condition. Conclusion. Cocaine use is a rare but identifiable factor that can cause giant bullous emphysema (GBE) resulting in severe complications and even death. The purpose of this case presentation is to support early identification and treatment of GBE using bullectomy with VATS, improving outcomes and decreasing morbidity and mortality

Patel-ISTH-15Jul2011IP_ToPrint.pptx-1.pdf

Occlusive thrombi that cause cardiovascular diseases form on the walls of blood vessels and propagate across the lumen under pressure gradient-driven flow, impaired antithrombotic, and enhanced prothrombotic conditions. Development of a well controlled and validated ex vivo model that can mimic these pathological conditions would provide a useful tool for the investigation of prothrombotic and antithrombotic molecular mechanisms, supplementing or replacing animal experimentationKeywords: Rational design, Ex vivo, Thrombosi

Rational Design of Ex Vivo Model of Thrombosis

Occlusive thrombi that cause cardiovascular diseases form on the walls of blood vessels and propagate across the lumen under pressure gradient-driven flow, impaired antithrombotic, and enhanced prothrombotic conditions. Development of a well controlled and validated ex vivo model that can mimic these pathological conditions would provide a useful tool for the investigation of prothrombotic and antithrombotic molecular mechanisms, supplementing or replacing animal experimentatio