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C Baldock

Publications and source records attributed to C Baldock.

At least 55 records · Page 3Linked to original sources
PubMed2000

Test liquids for quantitative MRI measurements of self-diffusion coefficient in vivo.

A range of liquids suitable as quality control test objects for measuring the accuracy of clinical MRI diffusion sequences (both apparent diffusion coefficient and tensor) has been identified and characterized. The self-diffusion coefficients for 15 liquids (3 cyclic alkanes: cyclohexane to cyclooctane, 9 n-alkanes: n-octane to n-hexadecane, and 3 n-alcohols: ethanol to 1-propanol were measured at 15-30 degrees C using an NMR spectrometer. Values at 22 degrees C range from 0.36 to 2.2 10(-9) m(2)s(-1). Typical 95% confidence limits are +/-2%. Temperature coefficients are 1.7-3.2% degrees C. T1 and T2 values at 1.5 T and proton density are given. n-tridecane has a diffusion coefficient close to that of normal white matter. The longer n-alkanes may be useful T2 standards. Measurements from a spin-echo MRI sequence agreed to within 2%.

Alcohols↗
PubMed2000

Effects of glass and backscatter on measurement of absorbed dose in polyacrylamide gel (PAG) dosimeters.

Different methodologies are used for calibrating polyacrylamide gel (PAG) dosimeters. One methodology involves injecting nitrogen-filled glass vials with polymer gel. Due to the vials being pre-filled with nitrogen, a nitrogen-filled space remains in the glass vial above the gel. The glass vial is then irradiated using ionizing radiation to polymerize the PAG. Monte Carlo simulations were performed to examine the effects on the radiation field due to the glass vial and the lack of backscatter material due to the nitrogen-filled space. Results for two different formulations of PAG indicated that the influence of the glass and the nitrogen-filled space are negligible.

Acrylic Resins↗
PubMed2000

Research software for radiotherapy gel dosimetry.

Gel dosimetry using magnetic resonance imaging is a technique which allows measurement of three-dimensional absorbed dose distributions in radiation therapy. This paper presents details of a software tool written specifically to provide facilities to perform image processing required in research and development of gel dosimetry. Collections of magnetic resonance images can be converted into either longitudinal or transverse nuclear magnetic resonance relaxation images. The conversions are accomplished by means of a pixel-by-pixel non-linear least squares fitting algorithm. Adjustments can be made to the number of parameters used in the fitting algorithm. Fundamental image manipulation tools such as window width/level display adjustment, zooming, profile and region of interest tools are provided. The software has been developed using MATLAB (The MathWorks Inc., Natick, MA) running on Windows 95. User interaction is via a windows graphical user interface (GUI). Data such as statistics from regions of interest can be exported to other windows applications for further processing. Flexibility is incorporated in the GUI design by taking advantage of the developmental aspects of the MATLAB environment. Although originally designed for gel dosimetry, the software can be used in any application of MRI which requires production and manipulation of relaxation time images.

Gels↗
PubMed1999

Molecular genetic analysis of enoyl-acyl carrier protein reductase inhibition by diazaborine.

Diazaborine and isoniazid are, at first sight, unrelated anti-bacterial agents that inhibit the enoyl-ACP reductase (ENR) of Escherichia coli and Mycobacterium tuberculosis respectively. The crystal structures of these enzymes including that of the diazaborine-inhibited E. coli ENR have been obtained at high resolution. Site-directed mutagenesis was used to study the importance of amino acid residues in diazaborine susceptibility and enzyme function. The results show that drug binding and inhibition require the presence of a glycine residue at position 93 of E. coli ENR or at the structurally equivalent position in the plant homologue, which is naturally resistant to the drug. The data confirm the hypothesis that any amino acid side-chain other than hydrogen at this position within the three-dimensional structure of these enzymes will affect diazaborine resistance by encroaching into the drug binding site. Substitutions of Gly-93 by amino acids with small side-chains, such as serine, alanine, cysteine and valine, hardly affected the catalytic parameters and rendered the bacterial host resistant to the drug. Larger amino acid side-chains, such as that of arginine, histidine, lysine and glutamine, completely inactivated the activity of the enzyme.

Alleles↗
PubMed1999

Uncertainty analysis in polymer gel dosimetry.

Verification of advanced radiotherapy treatment modalities requires measurement of three-dimensional absorbed dose distributions with high spatial resolution and precision. Polymer gel dosimeters combined with magnetic resonance imaging may be able to fulfil this requirement. However, verification requires that the uncertainty in the dosimeter is well known. One method of estimating the overall uncertainty in polymer gel dosimeters involves the propagation of the uncertainty in the R2 (nuclear magnetic resonance relaxation rate) map and the uncertainties in the calibration data. This work shows that using this method with current data suggests that the lowest uncertainty currently obtainable is about 3% at 8 Gy and 7% at 2 Gy. Furthermore, the most significant reductions in overall uncertainty will be achieved by reducing the noise in the R2 map.

Acrylic Resins↗
PubMed1999

A theoretical study of the radiological properties and water equivalence of Fricke and polymer gels used for radiation dosimetry.

A method is described which determines the radiological equivalence of different materials by comparing their macroscopic photon and electron interaction parameters over the energy range of interest. This method has been applied to Fricke and polymer gels used for radiation dosimetry. Photon and electron dose distributions were calculated using a Monte Carlo technique. 6 MV photon gel depth dose curves were all within 1% of those in water over the depth range studied. 6 MeV electron beam depth dose curves were all within 1 mm of those in water. The results show that for the gels investigated, at megavoltage energies the dominant property determining water equivalence is the electron density of the gel, and therefore future research into gel manufacture for external beam radiotherapy should aim to have the electron density (electrons per unit volume) as close as possible to water. However, care needs to be taken when using gels for dosimetry of photons with incident energy < 100 keV.

Electrons↗
PubMed1998

The X-ray structure of Escherichia coli enoyl reductase with bound NAD+ at 2.1 A resolution.

Enoyl acyl carrier protein reductase catalyses the last reductive step of fatty acid biosynthesis, reducing an enoyl acyl carrier protein to an acyl-acyl carrier protein with NAD(P)H as the cofactor. The crystal structure of enoyl reductase (ENR) from Escherichia coli has been determined to 2.1 A resolution using a combination of molecular replacement and isomorphous replacement and refined using data from 10 A to 2.1 A to an R-factor of 0.16. The final model consists of the four subunits of the tetramer, wherein each subunit is composed of 247 of the expected 262 residues, and a NAD+ cofactor for each subunit of the tetramer contained in the asymmetric unit plus a total of 327 solvent molecules. There are ten disordered residues per subunit which form a loop near the nucleotide binding site which may become ordered upon substrate binding. Each monomer is composed of a seven-stranded parallel beta-sheet flanked on each side by three alpha-helices with a further helix lying at the C terminus of the beta-sheet. This fold is highly reminiscent of the Rossmann fold, found in many NAD(P)H-dependent enzymes. Analysis of the sequence and structure of ENR and comparisons with the family of short-chain alcohol dehydrogenases, identify a conserved tyrosine and lysine residue as important for catalytic activity. Modelling studies suggest that a region of the protein surface that contains a number of strongly conserved hydrophobic residues and lies adjacent to the nicotinamide ring, forms the binding site for the fatty acid substrate.

Alcohol Dehydrogenase↗
PubMed1998

Mechanism of action of diazaborines.

The diazaborine family of compounds have antibacterial properties against a range of gram-negative bacteria. Initially, this was thought to be due to the prevention of lipopolysaccharide synthesis. More recently, the molecular target of diazaborines has been identified as the NAD(P)H-dependent enoyl acyl carrier protein reductase (ENR), which catalyses the last reductive step of fatty acid synthase. ENR from Mycobacterium tuberculosis is the target for the front-line antituberculosis drug isoniazid. The emergence of isoniazid resistance strains of M. tuberculosis, a chronic infectious disease that already kills more people than any other infection, is currently causing great concern over the prospects for its future treatment, and it has reawakened interest in the mechanism of diazaborine action. Diazaborines only inhibit ENR in the presence of the nucleotide cofactor, and this has been explained through the analysis of the x-ray crystallographic structures of a number of Escherichia coli ENR-NAD+-diazaborine complexes that showed the formation of a covalent bond between the boron atom in the diazaborines and the 2'-hydroxyl of the nicotinamide ribose moiety that generates a noncovalently bound bisubstrate analogue. The similarities in catalytic chemistry and in the conformation of the nucleotide cofactor across the wider family of NAD(P)-dependent oxidoreductases suggest that there are generic opportunities to mimic the interactions seen here in the rational design of bisubstrate analogue inhibitors for other NAD(P)H-dependent oxidoreductases.

Anti-Bacterial Agents↗
PubMed1998

Fourier transform Raman spectroscopy of polyacrylamide gels (PAGs) for radiation dosimetry.

Polyacrylamide gels (PAGs) are used for magnetic resonance imaging radiation dosimetry. Fourier transform (FT) Raman spectroscopy studies were undertaken to investigate cross-linking changes during the copolymerization of polyacrylamide gels in the spectral range of 200-3500 cm(-1). Vibrational bands of 1285 cm(-1) and 1256 cm(-1) were assigned to acrylamide and bis-acrylamide single CH2 deltaCH2 binding modes. Bands were found to decrease in amplitude with increasing absorbed radiation dose as a result of copolymerization. Principal component regression was performed on FT-Raman spectra of PAG samples irradiated to 50 Gy. Two components were found to be sufficient to account for 98.7% of the variance in the data. Cross validation was used to establish the absorbed radiation dose of an unknown PAG sample from the FT-Raman spectra. The calculated correlation coefficient between measured and predictive samples was 0.997 with a standard error of estimate of 0.976 and a standard error of prediction of 1.140. Results demonstrate the potential of FT-Raman spectroscopy for ionizing radiation dosimetry using polyacrylamide gels.

Acrylic Resins↗
PubMed1998

Experimental procedure for the manufacture and calibration of polyacrylamide gel (PAG) for magnetic resonance imaging (MRI) radiation dosimetry.

A simple methodology for the manufacture and calibration of polyacrylamide gel (PAG) for magnetic resonance imaging (MRI) radiation dosimetry is presented to enable individuals to undertake such work in a routine clinical environment. Samples of PAG were irradiated using a linear accelerator and imaged using a 0.5 T (22 MHz) Philips Gyroscan MRI scanner. The mean spin-lattice relaxation rate was measured using a 'turbo-mixed' sequence, consisting of a series of 90 degrees pulses, each followed by acquisition of a train of spin echoes. The mean sensitivity for five different batches of PAG in the range up to 10 Gy was calculated to be 0.0285 s-1 Gy-1 for the mean spin-lattice relaxation rate with a percentage standard deviation of 1.25%. The overall reproducibility between batches was calculated to be 2.69%. This methodology, which introduces the novel use of pre-filled nitrogen vials for calibration, has been used to develop techniques for filling anatomically shaped anthropomorphic phantoms.

Acrylic Resins↗
PubMed1997

Accident and emergency medicine--making waves on the Internet.

The internet is a communications and information tool which has recently entered the world of accident and emergency (A&E) medicine. It is a worldwide instrument facilitating the dissemination of ideas and clinical information in the specialty. It is being embraced by all disciplines involved in A&E medicine. Part I introduces the internet to those in A&E medicine unfamiliar with this technology. It describes the varied resources of the internet in A&E medicine and speculates on its future role. Part II supplies the reader with the necessary information to get on-line and explains some of the more technical aspects of the internet.

Computer Communication Networks↗
PubMed1996

A mechanism of drug action revealed by structural studies of enoyl reductase.

Enoyl reductase (ENR), an enzyme involved in fatty acid biosynthesis, is the target for antibacterial diazaborines and the front-line antituberculosis drug isoniazid. Analysis of the structures of complexes of Escherichia coli ENR with nicotinamide adenine dinucleotide and either thienodiazaborine or benzodiazaborine revealed the formation of a covalent bond between the 2' hydroxyl of the nicotinamide ribose and a boron atom in the drugs to generate a tight, noncovalently bound bisubstrate analog. This analysis has implications for the structure-based design of inhibitors of ENR, and similarities to other oxidoreductases suggest that mimicking this molecular linkage may have generic applications in other areas of medicinal chemistry.

Anti-Bacterial Agents↗
PubMed1996

Crystallization of Escherichia coli enoyl reductase and its complex with diazaborine.

Recent work has shown that the NADH-dependent enoyl acyl carrier protein reductase from Escherichia coli is the target for diazaborine, an antibacterial agent. This enzyme has been crystallized by the hanging-drop method of vapour diffusion complexed with NAD(+) and in the presence and absence of a thieno diazaborine. The crystals grown in the absence of diazaborine (form A) are in the space group P2(1) with unit-cell dimensions a = 74.0, b = 81.2, c = 79.0 A and beta = 92.9 degrees, and with a tetramer in the asymmetric unit, whilst those grown in the presence of diazaborine (form B) are in the space group P6(1)22 (or P6(5)22) with unit-cell dimensions a = b = 80.9 and c = 328.3 A, and with a dimer in the asymmetric unit. The structure determination of this enzyme in the presence of diazaborine will provide information on the nature of the drug binding site and contribute to a programme of rational drug design.

Journal Article↗
PubMed1996

A method for determining the diffusion coefficient in Fe(II/III) radiation dosimetry gels using finite elements.

Magnetic resonance imaging (MRI) may be used to image three-dimensional dose distributions of ionizing radiation in tissue equivalent gels infused with ferrous sulphate solutions, commonly known as Fricke gels. In this technique, ferrous (Fe2+) ions are oxidized to ferric (Fe3+) ions by free radicals produced by ionizing radiation. A limitation on this technique is the diffusion of ferric (Fe3+) ions in the gel. A method is presented for evaluating the diffusion coefficient in Fricke gels. Finite elements are used to model variations of the concentration in space, coupled with an analytical scheme to integrate the resulting system of equations through time. This method may be used for problems with one, two or three space dimensions and with arbitrary initial and boundary conditions. Results are presented for one- and two-dimensional data.

Diffusion↗
PubMed1995

Common themes in redox chemistry emerge from the X-ray structure of oilseed rape (Brassica napus) enoyl acyl carrier protein reductase.

BACKGROUND: Enoyl acyl carrier protein reductase (ENR) catalyzes the NAD(P)H-dependent reduction of trans-delta 2-enoyl acyl carrier protein, an essential step in de novo fatty acid biosynthesis. Plants contain both NADH-dependent and separate NADPH-dependent ENR enzymes which form part of the dissociable type II fatty acid synthetase. Highly elevated levels of the NADH-dependent enzyme are found during lipid deposition in maturing seeds of oilseed rape (Brassica napus). RESULTS: The crystal structure of an ENR-NAD binary complex has been determined at 1.9 A resolution and consists of a homotetramer in which each subunit forms a single domain comprising a seven-stranded parallel beta sheet flanked by seven alpha helices. The subunit has a topology highly reminiscent of a dinucleotide-binding fold. The active site has been located by difference Fourier analysis of data from crystals equilibrated in NADH. CONCLUSIONS: The structure of ENR shows a striking similarity with the epimerases and short-chain alcohol dehydrogenases, in particular, 3 alpha,20 beta-hydroxysteroid dehydrogenase (HSD). The similarity with HSD extends to the conservation of a catalytically important lysine that stabilizes the transition state and to the use of a tyrosine as a base--with subtle modifications arising from differing requirements of the reduction chemistry.

Amino Acid Sequence↗