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D Kell

Publications and source records attributed to D Kell.

10 recordsLinked to original sources

The use of nonlinear dielectric spectroscopy to monitor the bioelectromagnetic effects of a weak pulsed magnetic field in real time.

Nonlinear dielectric spectroscopy (NLDS) was used to detect interaction of a pulsed magnetic field (PMF) with membrane protein dynamics in aggregating Dictyostelium discoideum amoebae. In the experiments reported here, a strong nonlinear dielectric response of Dictyostelium discoideum cells is shown, and a distinctive nonlinear dielectric response of cells previously exposed to PMF is shown. The method of NLDS is shown to be capable of monitoring and charting the dynamic frequency response of the cell to an electromagnetic field.

Animals↗

A weak pulsed magnetic field affects adenine nucleotide oscillations, and related parameters in aggregating Dictyostelium discoideum amoebae.

A model eukaryotic cell system was used to explore the effect of a weak pulsed magnetic field (PMF) on time-varying physiological parameters. Dictyostelium discoideum cells (V12 strain) were exposed to a pulsed magnetic field (PMF) of flux density 0.4 mT, generated via air-cored coils in trains of 2 ms pulses gated at 20 ms. This signal is similar to those used to treat non-uniting fractures. Samples were taken over periods of 20 min from harvested suspensions of amoebae during early aggregation phase, extracted and derivatised for HPLC fluorescent assay of adenine nucleotides. Analysis of variance showed a significant athermal damping effect (P < 0.002, n = 22) of the PMF on natural adenine nucleotide oscillations and some consistent changes in phase relationships. The technique of nonlinear dielectric spectroscopy (NLDS) revealed a distinctive effect of PMF, caffeine and EGTA in modulating the cellular harmonic response to an applied weak signal. Light scattering studies also showed altered frequency response of cells to PMF, EGTA and caffeine. PMF caused a significant reduction of caffeine induced cell contraction (P < 0.0006, n = 19 by paired t-test) as shown by Malvern particle size analyser, suggesting that intracellular calcium may be involved in mediating the effect of the PMF.

Adenine Nucleotides↗

Non-linear optimization of biochemical pathways: applications to metabolic engineering and parameter estimation.

MOTIVATION: The simulation of biochemical kinetic systems is a powerful approach that can be used for: (i) checking the consistency of a postulated model with a set of experimental measurements, (ii) answering 'what if?' questions and (iii) exploring possible behaviours of a model. Here we describe a generic approach to combine numerical optimization methods with biochemical kinetic simulations, which is suitable for use in the rational design of improved metabolic pathways with industrial significance (metabolic engineering) and for solving the inverse problem of metabolic pathways, i.e. the estimation of parameters from measured variables. RESULTS: We discuss the suitability of various optimization methods, focusing especially on their ability or otherwise to find global optima. We recommend that a suite of diverse optimization methods should be available in simulation software as no single one performs best for all problems. We describe how we have implemented such a simulation-optimization strategy in the biochemical kinetics simulator Gepasi and present examples of its application. AVAILABILITY: The new version of Gepasi (3.20), incorporating the methodology described here, is available on the Internet at http://gepasi.dbs.aber.ac.uk/softw/Gepasi. html. CONTACT: prm@aber.ac.uk

Biochemistry↗

Expression of bcl-2 protein and Ki-67 nuclear proliferation antigen in benign and malignant cutaneous T-cell infiltrates.

The bcl-2 protein prolongs cell life by inhibiting apoptosis. Its expression has been studied in a variety of normal tissues and lymphomas but there is minimal information available concerning bcl-2 expression by benign and malignant cutaneous T-cells. Therefore, we investigated bcl-2 expression in a wide variety of cutaneous T-cell infiltrates using one- and two-color immunohistologic techniques. bcl-2 was expressed by the majority of lesional CD3+ T-cells in most cases. This included 22/26 cases of mycosis fungoides (MF), 3/3 cases of non-MF cutaneous T-cell lymphoma, 5/5 cases of lymphomatoid papulosis, 4/4 cases of T-cell rich cutaneous lymphoid hyperplasia, 2/3 cases of bullous pemphigoid, 2/2 cases of discoid lupus erythematosus and 1/1 case of lichen planus. Titration experiments and comparative studies of tonsil section positive controls revealed that, relative to mantle zone B-cells, there was over- expression of bcl-2 by a variable subset of T-cells in most cases. Assessment of multiple biopsies in a subset of MF cases showed stable expression of bcl-2 over intervals of up to two years. In contrast to the widespread expression of bcl-2 in both early and advanced MF skin lesions, abundant expression of the nuclear proliferation antigen, Ki-67, was skewed toward advanced MF skin lesions. Ten percent or more Ki-67+ cells were present in 5% of patients with patches/thin plaques, 38% with moderate plaques, 64% with thick plaques and 100% with tumor nodules.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗