Recently, we published the existence of 2 populations of anti– 2-glycoprotein I ( 2GPI) IgG antibodies. Type A antibodies recognize epitope G40-R43 in domain I of 2-GPI and are strongly associated with thrombosis. Type B antibodies recognize other parts of 2-GPI and are not associated with thrombosis. In this study we demonstrate that type A antibodies only recognize plasma-purified 2-GPI when ...

Thrombin is an important agonist for platelet activation and plays a major role in hemostasis and thrombosis. Thrombin activates platelets mainly through protease-activated receptor 1 (PAR1), PAR4, and glycoprotein Ib. Because adenosine diphosphate and thromboxane A2 have been shown to cause platelet aggregation by concomitant signaling through Gq and Gi pathways, we investigated whether coacti...

The effects of B-cell depletion with rituximab on regulatory T cells (Tregs) have not been determined. We investigated Tregs in patients receiving rituximab for chronic idiopathic thrombocytopenic purpura (ITP). The peripheral blood Tregs, identified as CD4 FOXP3 T cells, were measured by flow cytometry prior to and after the immunotherapy. In addition, Tregs were analyzed for their usage of th...

Thrombotic complications of vascular disease are the leading cause of morbidity and mortality in most industrialized countries. Despite this, safe and effective drugs targeting these complications are limited, especially in the chronic setting. This is because of the complexity of thrombosis in both arteries and veins, which is becoming increasingly evident as numerous factors are now known to ...

Recent observations have shown that Drm, a member the Dan family of bone morphogenic protein (BMP) antagonists, induces endothelial cell (EC) sprouting in vitro and angiogenesis in vivo by interacting with signaling EC receptors in a BMPindependent manner. Here, recombinant Drm (rDrm) up-regulates angiopoientin-1 (Ang-1) expression in EC without affecting Ang-2 and Tie-2 receptor expression. An...

Low-dose metronomic chemotherapy is a promising therapeutic cancer treatment strategy thought to have an antiangiogenic basis. However, the advantages of reduced toxicity, increased efficacy in some cases, and ability to combine chemotherapy administered long term in this way with targeted therapies can be compromised by the empiricism associated with determining the optimum biologic dose (OBD)...

Methylene tetrahydrofolate reductase (MTHFR) is an enzyme involved in the metabolism of homocysteine to methionine, and folic acid is an essential cofactor. Mutations in the MTHFR gene lead to hyperhomocysteinemia and vascular thrombosis. Heterozygous mutation involving a single nucleotide polymorphism in the MTHFR gene leading to vascular thrombosis is very rare. We present a case of segmental...

1Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston; 2Harvard–Massachusetts Institute of Technology (MIT) Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge; 3Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston; and 4Harvard Stem Cell I...

The 2 1 integrin is a major collagen receptor on platelets. Although it has been proposed that 2 1, like IIb 3, undergoes agonist-induced activation, neither the potential contributions of 2 1 receptor/ligand internalization to the increase in ligand binding nor the roles of the 2 and 1 cytoplasmic domains in activation of this integrin have been previously explored. Activation of 2 1 was asses...

Human protein S (PS), a cofactor of anticoagulant-activated protein C (APC), is a modular protein containing 4 epidermal growth factor (EGF)–like domains. EGF1 appears to mediate PS interaction with APC, but the roles of EGFs 2, 3, and 4 are less clear. We synthesized PS variants lacking single EGF domains (EGF2, 3, or 4) and assessed their APC cofactor activity in a factor Va inactivation assa...