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Biomedical subjects

G Lemon

Publications and source records attributed to G Lemon.

8 recordsLinked to original sources
PubMed2006

Multiphase modelling of cell behaviour on artificial scaffolds: effects of nutrient depletion and spatially nonuniform porosity.

This paper contains analysis of a recently formulated multiphase model for the growth of biological tissue that comprises motile cells and water inside a rigid scaffold material. The model is extended here to include a term describing cell proliferation which is mediated by the supply of a diffusible nutrient and to include the case where the scaffold porosity varies in space. Numerical solutions of the model equations are presented for different values of the parameters. Comparison is drawn between the different types of growth that arise when using static or dynamic methods for seeding the scaffold with cells. Analytical solutions are presented for the limiting cases in which the coefficient of drag between the cells and the scaffold is very large or zero. In the limit of large time, solutions reveal preferential tissue growth in the vicinity of the scaffold edge due to depletion of nutrient by the cells, consistent with experimental results. However, it is shown that reducing the coefficient of drag between the scaffold and the cells overcomes the effects of nutrient depletion by increasing cell mobility, thereby leading to improved uniformity of the cell distribution within the scaffold.

Algorithms↗
PubMed2004

Calcium mobilization and spontaneous transient outward current characteristics upon agonist activation of P2Y2 receptors in smooth muscle cells.

A quantitative model is provided that links the process of metabotropic receptor activation and sequestration to the generation of inositol 1,4,5-trisphosphate, the subsequent release of calcium from the central sarcoplasmic reticulum, and the consequent release of calcium from subsarcolemma sarcoplasmic reticulum that acts on large-conductance potassium channels to generate spontaneous transient outward currents (STOCs). This model is applied to the case of STOC generation in vascular A7r5 smooth muscle cells that have been transfected with a chimera of the P2Y(2) metabotropic receptor and green fluorescent protein (P2Y(2)-GFP) and exposed to the P2Y(2) receptor agonist uridine 5'-triphosphate. The extent of P2Y(2)-GFP sequestration from the membrane on exposure to uridine 5'-triphosphate, the ensuing changes in cytosolic calcium concentration, as well as the interval between STOCs that are subsequently generated, are used to determine parameter values in the model. With these values, the model gives a good quantitative prediction of the dynamic changes in STOC amplitude observed upon activation of metabotropic P2Y(2) receptors in the vascular smooth muscle cell line.

Animals↗
PubMed2003

Metabotropic receptor activation, desensitization and sequestration-I: modelling calcium and inositol 1,4,5-trisphosphate dynamics following receptor activation.

A mathematical account is given of the processes governing the time courses of calcium ions (Ca2+), inositol 1,4,5-trisphosphate (IP(3)) and phosphatidylinositol 4,5-bisphosphate (PIP(2)) in single cells following the application of external agonist to metabotropic receptors. A model is constructed that incorporates the regulation of metabotropic receptor activity, the G-protein cascade and the Ca2+ dynamics in the cytosol. It is subsequently used to reproduce observations on the extent of desensitization and sequestration of the P(2)Y(2) receptor following its activation by uridine triphosphate (UTP). The theory predicts the dependence on agonist concentration of the change in the number of receptors in the membrane as well as the time course of disappearance of receptors from the plasmalemma, upon exposure to agonist. In addition, the extent of activation and desensitization of the receptor, using the calcium transients in cells initiated by exposure to agonist, is also predicted. Model predictions show the significance of membrane PIP(2) depletion and resupply on the time course of IP(3) and Ca2+ levels. Results of the modelling also reveal the importance of receptor recycling and PIP(2) resupply for maintaining Ca2+ and IP(3) levels during sustained application of agonist.

Animals↗
PubMed2003

Metabotropic receptor activation, desensitization and sequestration-II: modelling the dynamics of the pleckstrin homology domain.

Recent observations have been made regarding the generation of inositol 1,4,5-trisphosphate (IP(3)), using chimeras of green fluorescent protein and the pleckstrin homology domain of phospholipase C-delta. In this paper a model is presented giving the quantitative relations between the green fluorescent protein-pleckstrin homology domain (GFP-PHD) construct and membrane phosphatidylinositol 4,5-bisphosphate (PIP(2)) levels as well as the concentration of IP(3), the product of hydrolysis of PIP(2). The model can correctly reproduce the dependence of cytosolic GFP-PHD fluorescence on IP(3) concentration. This model extends a previous one (Metabotropic receptor activation, desensitization and sequestration-I: modelling calcium and inositol 1,4,5-trisphosphate dynamics following receptor activation, in this issue) dealing with the processes governing the production of IP(3) and the subsequent calcium (Ca2+) changes in cells following activation of metabotropic receptors. This model is applied to the case of purinergic P(2)Y(2) receptor activation in Madin-Darby Canine Kidney (MDCK) cells with adenosine triphosphate (ATP) (Science 284 (1999) 1527). It is shown that it can correctly reproduce the dependence of GFP-PHD fluorescence on the concentration of P(2)Y(2) receptor ligand, as well as the temporal changes of GFP-PHD fluorescence following application of ligand.

Adenosine Triphosphate↗
PubMed2002

Neuronal cell death, nerve growth factor and neurotrophic models: 50 years on.

Viktor Hamburger has just died at the age of 100. It is 50 years since he and Rita Levi-Montalcini laid the foundations for the study of naturally occurring cell death and of neurotrophic factors in the nervous system. In a period of less than 10 years, from 1949 to 1958, Hamburger and Levi-Montalcini made the following seminal discoveries: that neuron cell death occurs in dorsal root ganglia, sympathetic ganglia and the cervical column of motoneurons; that the predictions arising from this observation, namely that survival is dependent on the supply of a trophic factor, could be substantiated by studying the effects of a sarcoma on the proliferation of ganglionic processes both in vivo and in vitro; and that the proliferation of these processes could be used as an assay system to isolate the factor. This work provides a short review mostly of the early history of this subject in the context of the Hamburger/Levi-Montalcini paradigm. This acts as an introduction to a consideration of models that have been proposed to account for how the different sources of growth factors provide for the survival of neurons during development. It is suggested that what has been called the 'social-control' model provides the most parsimonious quantitative description of the contribution of trophic factors to neuronal survival, a concept for which we are in debt to Viktor Hamburger and Rita Levi-Montalcini.

Animals↗
PubMed1989

Randomized study of adjusted versus fixed low dose heparin prophylaxis of deep vein thrombosis in hip surgery.

A randomized study of adjusted versus fixed low dose heparin prophylaxis has been conducted in 100 patients undergoing surgery for hip replacement or fractured neck of femur. The two types of patients were randomized independently into the adjusted and fixed dose regimens. Patients in the adjusted group were controlled by an activated partial thromboplastin time method particularly responsive to the anticoagulant effect of heparin. The aim was to maintain the peak value just above the upper limit of the normal range. Adjustment of dosage began 24 h after surgery in the replacement group and 24 h after admission in the fracture group. Significant improvement in protection against postoperative deep vein thrombosis, assessed by venography, was observed in the adjusted group undergoing hip replacement (P = 0.013) and overall in both groups (P = 0.017) compared with a conventional fixed dose subcutaneous regimen (calcium heparin 5000 units, 8-hourly). In most instances, adjustment resulted in increased heparin dosage but this was not associated with any evidence of excessive bleeding.

Adult↗