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Biomedical subjects

Robert A S Roubey

Publications and source records attributed to Robert A S Roubey.

8 recordsLinked to original sources
PubMed2005

Annexin A2: better left alone.

Zhang and McCrae demonstrate that APLA/b2GPI-mediated endothelial cell activation occurs via dimerization of annexin A2 molecules on the cell surface.

Animals↗
PubMed2004

Characterization of monocyte tissue factor activity induced by IgG antiphospholipid antibodies and inhibition by dilazep.

Increasing evidence suggests that autoantibodies directly contribute to hypercoagulability in the antiphospholipid syndrome (APS). One proposed mechanism is the antibody-induced expression of tissue factor (TF) by blood monocytes. Dilazep, an antiplatelet agent, is an adenosine uptake inhibitor known to block induction of monocyte TF expression by bacterial lipopolysaccharide. In the current study we characterized the effects of immunoglobulin G (IgG) from patients with APS on monocyte TF activity and investigated whether dilazep is capable of blocking this effect. IgG from 13 of 16 patients with APS significantly increased monocyte TF activity, whereas normal IgG had no effect. Time-course experiments demonstrated that APS IgG-induced monocyte TF mRNA levels were maximal at 2 hours and TF activity on the cell surface was maximal at 6 hours. Dilazep inhibited antibody-induced monocyte TF activity in a dose-dependent fashion but had no effect on TF mRNA expression. The effect of dilazep was blocked by theophylline, a nonspecific adenosine receptor antagonist. In conclusion, IgG from certain patients with APS induce monocyte TF activity. Dilazep inhibits the increased expression of monocyte TF activity at a posttranscriptional level, probably by way of its effect as an adenosine uptake inhibitor. Pharmacologic agents that block monocyte TF activity may be a novel therapeutic approach in APS.

Antibodies, Antiphospholipid↗
PubMed2004

Mechanisms of autoantibody-induced monocyte tissue factor expression.

The expression of tissue factor (TF) activity to flowing blood is the trigger for physiological coagulation as well as many types of thrombosis. A growing body of evidence suggests that increased tissue factor activity is a significant contributor towards the hypercoagulability associated with the antiphospholipid syndrome (APS). The increase in tissue factor activity appears to be due to increased transcription and translation of nascent tissue factor molecules but is not due to de-encryption of existing tissue factor molecules on cells. Autoantibodies and/or immune complexes circulating in APS patients appear to enhance the expression of tissue factor activity on monocytes and endothelial cells. Anti-beta2-glycoprotein I (beta2GPI) autoantibodies have been specifically implicated in the antibody-mediated enhancement of tissue factor activity. The presence of antibodies against tissue factor pathway inhibitor (TFPI) in certain APS patients suggests that negative regulation of tissue factor activity might also be impaired in these patients. Given a mechanism involving increased tissue factor activity in APS-associated thrombosis, agents specifically targeting tissue factor activity may be a novel and efficacious therapy that is safer than current approaches to the management of APS.

Antiphospholipid Syndrome↗
PubMed2002

Delayed apoptotic cell clearance and lupus-like autoimmunity in mice lacking the c-mer membrane tyrosine kinase.

Mice lacking the membrane tyrosine kinase c-mer have been shown to have altered macro-phage cytokine production and defective phagocytosis of apoptotic cells despite normal phagocytosis of other particles. We show here that c-mer-deficient mice have impaired clearance of infused apoptotic cells and that they develop progressive lupus-like autoimmunity, with antibodies to chromatin, DNA, and IgG. The autoimmunity appears to be driven by endogenous antigens, with little polyclonal B cell activation. These mice should be an excellent model for studying the role of apoptotic debris as an immunogenic stimulus for systemic autoimmunity.

Animals↗
PubMed2002

Treatment of the antiphospholipid syndrome.

Despite increasing knowledge of the immunology and pathophysiology of the antiphospholipid syndrome, treating this condition remains challenging. Because of a paucity of randomized controlled trials, many of the treatment recommendations are not evidence-based. Retrospective case series suggest that a high level of oral anticoagulation is needed to prevent recurrent thrombosis. The combination of heparin and low-dose aspirin is effective in significantly increasing the chances of a successful pregnancy in woman with recurrent pregnancy failure associated with antiphospholipid antibodies. Primary prevention with aspirin is justified in patients with antiphospholipid antibodies but without a prior history of thrombosis. Interesting and controversial issues in the treatment of the antiphospholipid syndrome include the use of less intensive anticoagulation or antiplatelet agents in some patient subsets, anticoagulation for certain nonstroke neurologic conditions, the role of other agents (hydroxychloroquine, antioxidants), and novel immunomodulatory strategies.

Abortion, Spontaneous↗