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Biomedical subjects

M Denyer

Publications and source records attributed to M Denyer.

13 recordsLinked to original sources
PubMed2000

Ordered networks of rat hippocampal neurons attached to silicon oxide surfaces.

The control of neuronal cell position and outgrowth is of fundamental interest in the development of applications ranging from cellular biosensors to tissue engineering. We have produced rectangular networks of functional rat hippocampal neurons on silicon oxide surfaces. Attachment and network formation of neurons was guided by a geometrical grid pattern of the adhesion peptide PA22-2 which matches in sequence a part of the A-chain of laminin. PA22-2 was applied by contact printing onto the functionalised silicon oxide surface and was immobilised by hetero-bifunctional cross-linking with sulfo-GMBS. Geometric pattern matching was achieved by microcontact printing using a polydimethylsiloxane (PDMS) stamp. In this way the produced grid pattern ranged from 3 to 20 microm in line width and from 50 to 100 microm in line distances. As shown by atomic force microscopy (AFM), line widths and line distances of the peptide pattern differ less than 0.5 microm from the used PDMS stamp. The height of the layer of immobilised PA22-2 was approximately 3.5 nm implying the layer to be monomolecular. Immobilised PA22-2 was capable of binding anti-PA22-2 antibodies indicating that the function of the peptide was not compromised by immobilisation. Rat hippocampal neurons, cultured at low density in serum-free medium, were applied to the growth matrix of PA22-2-coated substrates and, within 1-3 h of culture, formed a network-like pattern that more or less matched the printed grid. Reliability and reproducibility of neuronal network formation depended on the geometry, line width and node diameter of the grid pattern. The immobilised neurons showed resting membrane potentials comparable with controls and, already after 1 day of culture, were capable of eliciting action potentials. The suitability of the immobilised neurons for the study of man-made neural networks and for multi-site recordings from a functional neuronal network is discussed.

Animals↗
PubMed2000

The epithelial integrin alphavbeta6 is a receptor for foot-and-mouth disease virus.

Field isolates of foot-and-mouth disease virus (FMDV) have been shown to use the RGD-dependent integrin alphavbeta3 as a cellular receptor on cultured cells. However, several other RGD-dependent integrins may have the potential to act as receptors for FMDV in vivo. Of these, alphavbeta6 is a likely candidate for use as a receptor by FMDV as it is expressed on epithelial cells, which correlates with the tissue tropism of the virus. In this report, we show that human colon carcinoma cells (SW480) that are normally nonpermissive for FMDV become susceptible to infection as a result of transfection with the integrin beta6 subunit and expression of alphavbeta6 at the cell surface. Integrin alphavbeta6 is the major site for virus attachment on the beta6-transfected cells, and binding to alphavbeta6 serves to increase the rate of virus entry into these cells. In addition, we show that virus binding and infection of the beta6-transfected cells is mediated through an RGD-dependent interaction that is specifically inhibited by a monoclonal antibody (10D5) that recognizes alphavbeta6. These studies establish a role for alphavbeta6 as a cellular receptor for FMDV.

Animals↗
PubMed1999

Electrical recordings from rat cardiac muscle cells using field-effect transistors.

Extracellular electrophysiological recordings were made from cardiac cells cultured for up to seven days over microfabricated arrays of field-effect transistors. The recorded signals can be separated mainly into two types of cell transistor couplings: one that can be explained entirely by purely passive circuitry elements, and a second where voltage-gated ion channels contribute greatly to the measured extracellular signal.

Action Potentials↗
PubMed1998

Modulation of T cell and monocyte function in the spleen following infection of pigs with African swine fever virus.

Infection of pigs with many strains of African Swine Fever Virus (ASFV) has been shown to cause a loss or marked decrease in the ability of splenocytes to respond to mitogens. These observations have been extended by cell fractionation and reconstitution experiments to show that the mitogen stimulated proliferative capacity of both the CD4+ and CD8+ T cells is affected. Similarly, monocytes which are directly infectable by virus, are functionally defective as antigen presenting cells when added to mitogen stimulated normal T cells. Interestingly, the same T cells which respond poorly in mitogenic assays can be activated by stimulation through the CD3 receptor. In contrast to the defective mitogenic response of T cells, B cell function, as assessed by stimulation through the CD40 ligand in vitro remains intact. There is no evidence for apoptosis in either the T cells or the B cells recovered from the spleens of ASFV infected animals 1-5 days following infection. Although the number of leucocytes which can be recovered from the infected spleen decreases rapidly with progression of the disease, the proportion of the different cell phenotypes remains constant. Thus decreased activity of lymphocytes in lymphoid tissue from ASFV infected animals appears to be directly attributable to infection of the monocytes.

African Swine Fever Virus↗
PubMed1997

Adhesion, orientation, and movement of cells cultured on ultrathin fibronectin fibers.

This study examined the behavior of rat tendon fibroblasts, baby hamster kidney fibroblasts, macrophage-like P388D1 cells, and neurons from rat dorsal root ganglia, cultured on fibronectin strands 0.2-5 micrograms in diameter. We investigated cell spreading, orientation, formation of focal contacts, the speed of cell movement, and the speed of neurite outgrowth in cells cultured on fibronectin strands, glass covered with fibronectin, and plain, nontreated glass. Fibronectin strands significantly promoted cell spreading and caused a marked alignment of all kinds of cells to the direction of the fiber. The fibers caused the alignment of actin filaments in fibroblasts and focal contacts in fibroblasts and macrophages and increased polymerization of F-actin in cells. Fibronectin fibers also increased the speed and persistence of cell movement and the rate of neurite outgrowth. Macrophages grown on fibronectin fibers produced numerous actin-rich microspikes and adopted a polarized, migratory phenotype. These findings indicate that fibronectin strands, resembling natural components of the extracellular matrix, are more effective in activating various types of cells then two-dimensional, fibronectin-covered substrata. The results also confirm the suitability of the three-dimensionally oriented fibronectin form for use in clinical practice.

Actins↗
PubMed1996

PEG -- is the E necessary? A comparison of percutaneous and endoscopic gastrostomy.

We describe our experience of 45 percutaneous gastrostomies using 12 F Wills-0glesby (Cook, Inc, Bloomington, IN, USA) catheters and 33 percutaneous endoscopic gastrostomies using 12 F Bower PEG's (Corpak, Inc, Wheeling, IL, USA). Tube displacement was a continued problem with the Wills-Oglesby catheter resulting in three patients developing peritonitis with one death. In view of this we would recommend as the preferred technique the endoscopic placement of Bower PEG catheters unless there are contraindications to the endoscopic technique.

Catheterization↗
PubMed1991

Inhibition of T and B lymphocyte proliferation by rapamycin.

The immunosuppressive macrolide rapamycin shows marked structural similarity to FK-506, and like FK-506 inhibits the activation of cultured T and B lymphocytes at concentrations as low as 10(-10) M. However, rapamycin blocks T-lymphocyte proliferation at a much later stage than FK-506. It also inhibits human, porcine and murine T- and B-lymphocyte activation by all pathways tested, including pathways which are insensitive to FK-506, such as interleukin-2 (IL-2)-mediated proliferation of IL-2-dependent T-cell lines, activation of human peripheral blood T lymphocytes by phorbol ester and anti-CD28 and activation of murine B lymphocytes by bacterial lipopolysaccharide. Thus these two macrolides that bind competitively to the same major intracellular receptor protein inhibit T- and B-lymphocyte activation by quite distinct mechanisms.

Animals↗
PubMed1982

Ranitidine heals duodenal ulcers.

A double-blind placebo-controlled study of ranitidine 150 mg given twice daily for 4 weeks was carried out in 80 ambulant patients with endoscopically proven duodenal ulceration. Fifteen patients were withdrawn because of poor compliance or default. Of the remaining 65 patients, endoscopic healing (with or without residual erosion) was noted in 28 of the 34 ranitidine-treated patients (82%) and in 14 of the 31 placebo-treated patients (45%) (P less than 0.005). Twenty-three patients whose ulcers were unhealed after 4 weeks of ranitidine therapy or placebo were then given ranitidine for a further 4-week period. Four of these patients were withdrawn, but ulcer healing was achieved in 16 of the remaining 19 patients (4 out of 5 (80%) initially treated with ranitidine and 12 of 14 (86%) initially treated with placebo). No significant clinical, biochemical or haematological adverse reactions were noted in either treatment group. It is concluded that ranitidine is a safe and effective therapy in patients with duodenal ulceration and that initial unsuccessful treatment with placebo does not appear to influence the subsequent response to ranitidine.

Adult↗
PubMed1982

Antigenic properties of some equine influenza viruses.

The antigenic relationships between the haemagglutinins of five A/equine-1 viruses and between six A/equine-2 viruses were examined using post-infection ferret and immunized pony sera. Similar results were obtained with sera from both species for the A/equine-1 viruses and these confirmed minor antigenic differences between the prototype A/Prague 1/56 virus and viruses isolated in England in 1973 and 1977. Considerable antigenic differences were found between five of the A/equine-2 viruses, using ferret sera, but these differences were less evident using pony sera. The response of ponies to the inactivated viruses indicated that there was little need to change the virus strains used in the manufacture of commercial equine influenza vaccines.

Animals↗
PubMed1981

Field and laboratory studies of equine influenza viruses isolated in 1979.

Experimental ponies developed signs of disease four days after the intranasal instillation of A/England 1/79 equine influenza virus and virus was recovered from the nasopharynx from the second to the ninth day. No significant antigenic difference was found between the virus and the prototype A/Miami 1/63 virus, using post infection ferret and chicken sera and post vaccination pony sera. No antigenic differences were found between four viruses isolated between January and July 1979, although some differences were found in their ability to detect haemagglutination inhibiting antibody in convalescent horse sera.

Animals↗