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Search Results: 1 - 10 of 13 matches for " Lakey JRT "
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Islet Isolation and Transplantation from an Annular Pancreas: A Case Report
Kin T,Shapiro J,Ryan EA,Lakey JRT
JOP Journal of the Pancreas , 2005,
Abstract: CONTEXT: Annular pancreas is an uncommon congenital anomaly formed by a thin band of normal pancreatic tissue encircling the duodenum. CASE REPORT: We report the first case of an islet isolation and transplantation from an annular pancreas. The pancreas together with duodenum was procured from a 32-year-old previously healthy man after diagnosis of brain death. The pancreas including the annular portion was distended well after intraductal collagenase perfusion. A total of 276,064 islet equivalent was recovered and transplanted into a type 1 diabetic patient. CONCLUSIONS: Bearing in mind the shortage of donors, patients with this anomalous condition should not be excluded as potential organ donors.
Divergence-Free Multiwavelets on the Half Plane
Joseph Lakey,Phan Nguyen
Axioms , 2013, DOI: 10.3390/axioms2020100
Abstract: We use the biorthogonal multiwavelets related by differentiation constructed in previous work to construct compactly supported biorthogonal multiwavelet bases for the space of vector fields on the upper half plane R2 + such that the reconstruction wavelets are divergence-free and have vanishing normal components on the boundary of R2 +. Such wavelets are suitable to study the Navier–Stokes equations on a half plane when imposing a Navier boundary condition.
Self-Assembly of Protein Monolayers Engineered for Improved Monoclonal Immunoglobulin G Binding
Anton P. Le Brun,Deepan S. H. Shah,Dale Athey,Stephen A. Holt,Jeremy H. Lakey
International Journal of Molecular Sciences , 2011, DOI: 10.3390/ijms12085157
Abstract: Bacterial outer membrane proteins, along with a filling lipid molecule can be modified to form stable self-assembled monolayers on gold. The transmembrane domain of Escherichia coli outer membrane protein A has been engineered to create a scaffold protein to which functional motifs can be fused. In earlier work we described the assembly and structure of an antibody-binding array where the Z domain of Staphylococcus aureus protein A was fused to the scaffold protein. Whilst the binding of rabbit polyclonal immunoglobulin G (IgG) to the array is very strong, mouse monoclonal IgG dissociates from the array easily. This is a problem since many immunodiagnostic tests rely upon the use of mouse monoclonal antibodies. Here we describe a strategy to develop an antibody-binding array that will bind mouse monoclonal IgG with lowered dissociation from the array. A novel protein consisting of the scaffold protein fused to two pairs of Z domains separated by a long flexible linker was manufactured. Using surface plasmon resonance the self-assembly of the new protein on gold and the improved binding of mouse monoclonal IgG were demonstrated.
Controlled spatial and conformational display of immobilised bone morphogenetic protein-2 and osteopontin signalling motifs regulates osteoblast adhesion and differentiation in vitro
Elizabeth A Mitchell, Benjamin T Chaffey, Andrew W McCaskie, Jeremy H Lakey, Mark A Birch
BMC Biology , 2010, DOI: 10.1186/1741-7007-8-57
Abstract: A protein was engineered to contain a C-terminal cysteine that would allow chemisorption to gold, followed by 12 amino acids that form a water soluble coil that could switch to a hydrophobic helix in the presence of alkane thiols. Bioactive motifs from either bone morphogenetic protein-2 or osteopontin were added to this scaffold protein and when assembled on a gold surface assessed for their ability to influence cell function. Data demonstrate that osteoblast adhesion and short-term responsiveness to bone morphogenetic protein-2 is dependent on the surface density of a cell adhesive motif derived from osteopontin. Furthermore an immobilised cell interaction motif from bone morphogenetic protein supported bone formation in vitro over 28 days (in the complete absence of other osteogenic supplements). In addition, two-dimensional patterning of this ligand using a soft lithography approach resulted in the spatial control of osteogenesis.These data describe an approach that allows the influence of immobilised protein ligands on cell behaviour to be dissected at the molecular level. This approach presents a durable surface that allows both short (hours or days) and long term (weeks) effects on cell activity to be assessed. This widely applicable approach can provide mechanistic insight into the contribution of immobilised ligands in the control of cell activity.It has long been recognised that cell regulatory molecules, such as growth factors and cytokines, exert powerful influences on the behaviour of eukaryotic cells at the interface of tissues. Indeed the immobilized activity of these signalling mediators in combination with the extracellular matrix (ECM) underpins many fundamental biological processes including embryo-, morpho- and tumorogenesis and wound healing [1]. Numerous studies have established the principle that tethered ligands regulate cell behavior quite distinctly from their freely diffusible counterpart. For example, extracellular matrix proteins like fi
A Comprehensive Clinicopathologic Analysis Suggests that Vascular Endothelial Growth Factor (VEGF) is the Most Likely Mediator of Periosteal New Bone Formation (PNBF) Associated with Diverse Etiologies
Meredith A. Lakey, Michael J. Klein and Ona M. Faye-Petersen
Clinical Medicine Insights: Arthritis and Musculoskeletal Disorders , 2012,
Abstract: Periosteal new bone formation (PNBF) is the means by which appositional bone growth normally takes place on the surfaces of compact bone. Alterations in the periosteal microenvironment trigger complex interactions between osteoblasts and endothelial cells to promote PNBF. Physiologic processes like mechanical stress result in normal PNBF; but, a variety of pathologic processes result in excessive PNBF. The production of sufficient bone to be detectable by conventional radiography is a common feature of diverse etiologies, including infection; inflammation; prostaglandin E2 administration for ductal-dependent congenital heart disease; metabolic and hormonal abnormalities; neoplasms; fracture repair; systemic hypoxia; and hypertrophic osteoarthropathy. While the clinical settings and distribution of affected bone sites in these conditions are different, the histopathology of the PNBF is essentially identical; so, it seems logical that a common pathway might mediate them all. By combining the observations and insights gained from osseous research and studying the clinical pathology of these diverse conditions, we constructed a comprehensive pathway to explain PNBF. In doing so, it seems likely that Vascular Endothelial Growth Factor (VEGF) is the most likely common mediator of the pathways that lead to PNBF.
A generic expression system to produce proteins that co-assemble with alkane thiol SAM
Benjamin T Chaffey,Elizabeth Mitchell,Mark A Birch,Jeremy H Lakey
International Journal of Nanomedicine , 2008,
Abstract: Benjamin T Chaffey1, Elizabeth Mitchell1, Mark A Birch2, Jeremy H Lakey11The Institute for Cell and Molecular Biosciences; 2The School of Surgical and Reproductive Sciences, The Medical School, Framlington Place, The University of Newcastle-upon-Tyne, Newcastle-upon-Tyne, Great BritainAbstract: Surface biology aims to observe and control biological processes by combining bio-, surface, and physical chemistry. Self-assembled monolayers (SAM) on gold surfaces have provided excellent methods for nanoscale surface preparation for such studies. However, extension of this work requires the specific immobilization of whole protein domains and the direct incorporation of recombinant proteins into SAM is still problematic. In this study a short random coil peptide has been designed to insert into thioalkane layers by formation of a hydrophobic helix. Surface plasmon resonance (SPR) studies show that specific immobilization via the internal cysteine is achieved. Addition of the peptide sequence to the terminus of a protein at the genetic level enables the production of a range of recombinant fusion-proteins with good yield. SPR shows that the proteins display the same gold-binding behavior as the peptide. It is shown that cell growth control can be achieved by printing the proteins using soft lithography with subsequent infilling with thio-alkanes The expression plasmid is constructed so that any stable protein domain can be easily cloned, expressed, purified and immobilized.Keywords: self-assembling monolayer, protein immobilization, nanotechnology, circular dichroism spectroscopy, surface plasmon resonance, osteoblast
A Comprehensive Clinicopathologic Analysis Suggests that Vascular Endothelial Growth Factor (VEGF) is the Most Likely Mediator of Periosteal New Bone Formation (PNBF) Associated with Diverse Etiologies
Meredith A. Lakey,Michael J. Klein,Ona M. Faye-Petersen
Clinical Medicine : Arthritis and Musculoskeletal Disorders , 2008,
Abstract: Periosteal new bone formation (PNBF) is the means by which appositional bone growth normally takes place on the surfaces of compact bone. Alterations in the periosteal microenvironment trigger complex interactions between osteoblasts and endothelial cells to promote PNBF. Physiologic processes like mechanical stress result in normal PNBF; but, a variety of pathologic processes result in excessive PNBF. The production of sufficient bone to be detectable by conventional radiography is a common feature of diverse etiologies, including infection; inflammation; prostaglandin E2 administration for ductal-dependent congenital heart disease; metabolic and hormonal abnormalities; neoplasms; fracture repair; systemic hypoxia; and hypertrophic osteoarthropathy. While the clinical settings and distribution of affected bone sites in these conditions are different, the histopathology of the PNBF is essentially identical; so, it seems logical that a common pathway might mediate them all. By combining the observations and insights gained from osseous research and studying the clinical pathology of these diverse conditions, we constructed a comprehensive pathway to explain PNBF. In doing so, it seems likely that Vascular Endothelial Growth Factor (VEGF) is the most likely common mediator of the pathways that lead to PNBF.
Baseline serum MMP-3 levels in patients with Rheumatoid Arthritis are still independently predictive of radiographic progression in a longitudinal observational cohort at 8 years follow up
Mark Houseman, Catherine Potter, Nicola Marshall, Rachel Lakey, Tim Cawston, Ian Griffiths, Steven Young-Min, John D Isaacs
Arthritis Research & Therapy , 2012, DOI: 10.1186/ar3734
Abstract: Fifty-eight of the original cohort (n = 118) had radiographic progression from baseline to mean 8.2-years determined using the van der Heijde modified Sharp method. The contribution of each predictor variable towards radiographic progression was assessed with univariate and multivariate analyses.Traditional factors (including erythrocyte sedimentation rate, C-reactive protein, anti-cyclic citrullinated peptide (anti-CCP), and rheumatoid factor) and biomarkers of tissue destruction (including MMP-3, C-telopeptide of type II collagen, cartilage oligomeric matrix protein, and tissue inhibitor of metalloproteinase 1) measured at baseline were associated with radiographic progression at endpoint. Multivariate logistic regression identified anti-CCP seropositivity [OR 9.29, 95%CI: 2.29-37.64], baseline elevated MMP-3 [OR 8.25, 95%CI: 2.54-26.78] and baseline radiographic damage [OR 5.83, 95%CI: 1.88-18.10] as the strongest independent predictors of radiographic progression. A model incorporating these variables had a predictive accuracy of 0.87, assessed using the area under the receiver operating characteristic curve.In our cohort with onset of RA symptoms < 2-years, multivariate analysis identified anti-CCP status and baseline MMP-3 as the strongest independent predictors of radiographic disease outcome at 8.2-years. This finding suggests determination of baseline MMP-3, in conjunction with traditional serologic markers, may provide additional prognostic information for patients with RA. Furthermore, these findings highlight the importance of continued research into a broad range of biomarkers as potential predictors of joint damage.Current paradigms for management of patients with rheumatoid arthritis (RA) dictate early aggressive therapy in treatment-to-target strategies, aiming for remission of symptoms [1]. In turn this prevents joint destruction and associated co-morbidities, including cardiovascular complications. A particular concern regarding these principles, h
Toward Low-Cost Affinity Reagents: Lyophilized Yeast-scFv Probes Specific for Pathogen Antigens
Sean A. Gray, Kris M. Weigel, Ibne K. M. Ali, Annie A. Lakey, Jeremy Capalungan, Gonzalo J. Domingo, Gerard A. Cangelosi
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0032042
Abstract: The generation of affinity reagents, usually monoclonal antibodies, remains a critical bottleneck in biomedical research and diagnostic test development. Recombinant antibody-like proteins such as scFv have yet to replace traditional monoclonal antibodies in antigen detection applications, in large part because of poor performance of scFv in solution. To address this limitation, we have developed assays that use whole yeast cells expressing scFv on their surfaces (yeast-scFv) in place of soluble purified scFv or traditional monoclonal antibodies. In this study, a nonimmune library of human scFv displayed on the surfaces of yeast cells was screened for clones that bind to recombinant cyst proteins of Entamoeba histolytica, an enteric pathogen of humans. Selected yeast-scFv clones were stabilized by lyophilization and used in detection assay formats in which the yeast-scFv served as solid support-bound monoclonal antibodies. Specific binding of antigen to the yeast-scFv was detected by staining with rabbit polyclonal antibodies. In flow cytometry-based assays, lyophilized yeast-scFv reagents retained full binding activity and specificity for their cognate antigens after 4 weeks of storage at room temperature in the absence of desiccants or stabilizers. Because flow cytometry is not available to all potential assay users, an immunofluorescence assay was also developed that detects antigen with similar sensitivity and specificity. Antigen-specific whole-cell yeast-scFv reagents can be selected from nonimmune libraries in 2–3 weeks, produced in vast quantities, and packaged in lyophilized form for extended shelf life. Lyophilized yeast-scFv show promise as low cost, renewable alternatives to monoclonal antibodies for diagnosis and research.
Histone deacetylase inhibitors modulate metalloproteinase gene expression in chondrocytes and block cartilage resorption
David A Young, Rachel L Lakey, Caroline J Pennington, Debra Jones, Lara Kevorkian, Dylan R Edwards, Timothy E Cawston, Ian M Clark
Arthritis Research & Therapy , 2005, DOI: 10.1186/ar1702
Abstract: Articular cartilage is made up of two main extracellular-matrix (ECM) macromolecules, namely, type II collagen and aggrecan (a large, aggregating proteoglycan) [1,2]. The type II collagen scaffold endows the cartilage with its tensile strength, while the aggrecan, by virtue of its high negative charge, draws water into the tissue, swelling against the collagen network, and enabling the tissue to resist compression. Quantitatively more minor components (e.g. types IX, XI, and VI collagens; biglycan; decorin; cartilage oligomeric matrix protein; etc.) also have important roles in controlling matrix structure and organisation [2].Normal cartilage ECM is in a state of dynamic equilibrium, with a balance between synthesis and degradation. For the degradative process, the major players are metalloproteinases that degrade the ECM, and their inhibitors. Pathological cartilage destruction can therefore be viewed as a disruption of this balance, favouring proteolysis.The matrix metalloproteinases (MMPs) are a family of 23 enzymes in man that facilitate turnover and breakdown of the ECM in both physiology and pathology. The MMP family contains the only mammalian proteinases that can specifically degrade the collagen triple helix at neutral pH. These include the 'classical' collagenases – MMP-1, -8, and -13 – and also MMP-2 and MMP-14 (which cleave the triple helix with less catalytic efficiency). The enzyme(s) responsible for cartilage collagen cleavage in the arthritides remains open to debate [3].A second group of metalloproteinases, the ADAMTS (a disintegrin and metalloproteinase domain with thrombospondin motifs) family, consists of 19 members, including the so-called 'aggrecanases', currently ADAMTS-1, -4, -5, -8, -9, and -15 [4-7]. Current data support the hypothesis that aggrecanases are active early in the disease process, with later increases in MMP activity (several MMPs can also degrade aggrecan), but the exact enzyme(s) responsible for cartilage aggrecan destructio
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