18 research outputs found
Embeddings and -envelopes of exact operator systems
We prove a necessary and sufficient condition for embeddability of an
operator system into . Using Kirchberg's theorems on a tensor
product of and , we establish results on
their operator system counterparts and .
Applications of the results proved, including some examples describing
-envelopes of operator systems, are also discussed.Comment: 12 Pages. To appear in Bulletin of the Australian Mathematical
Societ
Immunodiagnosis of platelet activation in immune thrombocytopenia through scFv antibodies cognate to activated IIb3 integrins
Fibrotic Remodeling of the Extracellular Matrix through a Novel (Engineered, Dual-Function) Antibody Reactive to a Cryptic Epitope on the N-Terminal 30 kDa Fragment of Fibronectin
<div><p>Fibrosis is characterized by excessive accumulation of scar tissue as a result of exaggerated deposition of extracellular matrix (ECM), leading to tissue contraction and impaired function of the organ. Fibronectin (Fn) is an essential component of the ECM, and plays an important role in fibrosis. One such fibrotic pathology is that of proliferative vitreoretinopathy (PVR), a sight-threatening complication which develops as a consequence of failure of surgical repair of retinal detachment. Such patients often require repeated surgeries for retinal re-attachment; therefore, a preventive measure for PVR is of utmost importance. The contractile membranes formed in PVR, are composed of various cell types including the retinal pigment epithelial cells (RPE); fibronectin is an important constituent of the ECM surrounding these cells. Together with the vitreous, fibronectin creates microenvironments in which RPE cells proliferate. We have successfully developed a dual-action, fully human, fibronectin-specific single chain variable fragment antibody (scFv) termed Fn52RGDS, which acts in two ways: i) binds to cryptic sites in fibronectin, and thereby prevents its self polymerization/fibrillogenesis, and ii) interacts with the cell surface receptors, ie., integrins (through an attached “RGD” sequence tag), and thereby blocks the downstream cell signaling events. We demonstrate the ability of this antibody to effectively reduce some of the hallmark features of fibrosis - migration, adhesion, fibronectin polymerization, matrix metalloprotease (MMP) expression, as well as reduction of collagen gel contraction (a model of fibrotic tissue remodeling). The data suggests that the antibody can be used as a rational, novel anti-fibrotic candidate.</p></div
Changes in cell viability and proliferation in the presence of Fn52 and Fn52RGDS.
<p>Panel A: D407 RPE cell viability assessed by the MTT assay. The optical density of the wells containing cells seeded in the presence of patient vitreous/SRF was assigned as 100%. Panel B: RPE cell proliferation was assessed by the BrdU assay. PV (assigned as 100%) represents conditioned media obtained from cells grown in the presence of patient vitreous (and subretinal fluid). In both the assays, the control scFv O27 was also used; the effect of the scFv antibodies was evaluated, using a range of concentrations. Each bar represents mean±SEM (standard error of the mean) calculated from five and three separate experiments respectively.</p
Analysis of collagen gel contraction in the presence of the scFv antibodies.
<p>Collagen gel contraction was performed using HT-1080 cells, to evaluate contraction of gel in the absence of any added scFv, or in the presence of either O27 or Fn52 or Fn52RGDS. Pictures were recorded 4 h after overlaying with media (representative image of four separate experiments) (Panel A). The area of the collagen gels was measured and expressed as gel/well ratio (%). The data is represented as mean±SEM (standard error of the mean) calculated from four separate experiments (Panel B).</p
A schematic diagram to illustrate the modular structure of fibronectin, sites of interaction of some of the known anti-fibronectin antibodies, and the proposed dual action of the scFv antibody, Fn52RGDS.
<p>The double arrow indicates the interaction of the cell surface integrin with the “RGD” residues of fibronectin.</p
The importance of fibronectin matrix assembly in various cellular processes.
<p>Fibronectin matrix assembly regulates cell growth, cell matrix adhesion, cellular contraction, and matrix metalloproteases (MMP) expression. Decreased fibrillogenesis resulting in decreased MMP expression may itself also be responsible for inhibition of cellular contraction. The scFv Fn52RGDS acts in accordance with features suggestive of decreased fibrillogenesis.</p