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Biomedical subjects

J R Mitchell

Publications and source records attributed to J R Mitchell.

At least 19 recordsLinked to original sources
PubMed2005

Resolution-dependent estimates of multiple sclerosis lesion loads.

BACKGROUND: Changes in brain lesion loads assessed with magnetic resonance imaging obtained at 1.5 Telsa (T) are used as a measure of disease evolution in natural history studies and treatment trials of multiple sclerosis. METHODS: A comparison was made between the total lesion volume and individual lesions observed on 1.5 T images and on high-resolution 4 T images. Lesions were quantified using a computer-assisted segmentation tool. RESULTS: There was a 46% increase in the total number of lesions detected with 4 T versus 1.5 T imaging (p < 0.005). The 4 T also showed a 60% increase in total lesion volume when compared with the 1.5 T (p < 0.005). In several instances, the 1.5 T scans showed individual lesions that coalesced into larger areas of abnormality in the 4 T scans. The relationship between individual lesion volumes was linear (slope 1.231) showing that the lesion volume observed at 4 T increased with the size of the lesion detected at 1.5 T. The 4 T voxels were less than one quarter the size of those used at 1.5 T and there were no consistent differences between their signal-to-noise ratios. CONCLUSIONS: The increase in signal strength that accompanied the increase in field strength compensated for the loss in signal amplitude produced by the use of smaller voxels. This enabled the acquisition of images with improved resolution, resulting in increased lesion detection at 4 T and larger lesion volumes.

Adult↗
PubMed2004

Fitting of the beat pattern observed in NMR free-induction decay signals of concentrated carbohydrate-water solutions.

A series of mathematical functions has been used to fit the proton free-induction decays (FIDs) of concentrated carbohydrate-water samples. For the solid protons, these functions included a sinc function, as well as the Fourier transforms of single and multiple Pake functions multiplied by a Gaussian broadening. The NMR signal from the mobile protons is described by an exponential function. It is found that in most cases the sinc function gives a satisfactory result and provides valuable information about the second moment M(2) and the ratio of solid to mobile protons (f(s) / f(m)). A good indication for using the sinc function is the presence of a beat in the FID. For high temperatures this approach breaks down, and a biexponential fit is more appropriate. If a clear dipolar splitting is observable in the NMR spectra, the Pake function (or a multiple Pake fit) should be used. In this case information about M(2) and f(s) / f(m) can also be obtained.

Algorithms↗
PubMed2003

A new local multiscale Fourier analysis for medical imaging.

The Stockwell transform (ST), recently developed for geophysics, combines features of the Fourier, Gabor and wavelet transforms; it reveals frequency variation over time or space. This valuable information is obtained by Fourier analysis of a small segment of a signal at a time. Localization of the Fourier spectrum is achieved by filtering the signal with frequency-dependent Gaussian scaling windows. This multi-scale time-frequency analysis provides information about which frequencies occur and more importantly when they occur. Furthermore, the Stockwell domain can be directly inferred from the Fourier domain and vice versa. These features make the ST a potentially effective tool to visualize, analyze, and process medical imaging data. The ST has proven useful in noise reduction and tissue texture analysis. Herein, we focus on the theory and effectiveness of the ST for medical imaging. Its effectiveness and comparison with other linear time-frequency transforms, such as the Gabor and wavelet transforms, are discussed and demonstrated using functional magnetic resonance imaging data.

Algorithms↗
PubMed2002

Organisation of the external region of the starch granule as determined by infrared spectroscopy.

Attenuated total reflectance-Fourier transform infrared (ATR-FTIR) was used to study the external regions of starch granules. Native starches (wheat, potato, maize, waxy maize and amylomaize) were analysed and compared to gelatinised and acid-hydrolysed starches. The IR spectra of potato and amylomaize starches were closer to that of highly ordered acid-hydrolysed starch than the other starches. FTIR was not able to differentiate between A- and B-type crystallinity so the difference observed between starches was not related to this factor. The variation between starch varieties was interpreted in terms of the level of ordered structure present on the edge of starch granules with potato and amylomaize being more ordered on their outer regions. This could explain the high resistance of both these starches to enzyme hydrolysis.

Acids↗
PubMed2002

Improved contrast in multispectral phase images derived from magnetic resonance exams of multiple sclerosis patients.

We describe a method to extract data from multispectral MR exams of patients with Multiple Sclerosis (MS). The technique produces images of "spectral phase" (SP) relative to a reference tissue. SP images allow retrospective suppression of signal in the reference tissue, while maintaining high spatial resolution. Image quality in SP images was determined from MR exams of 5 MS patients selected at random from a clinical trial underway at our institute. Exams consisting of proton density weighted (PDw), T2 weighted (T2w), T1 weighted (T1w), and gadolinium-DTPA enhanced T1w (GAD) images were acquired from each patient. The MR exams were corrected for intensity nonuniformity, then filtered with an algorithm based upon anisotropic diffusion, to reduce noise. Principal component (PC) images and SP images relative to cerebrospinal fluid (SP(CSF)), normal appearing white matter (SP(NAWM)), gray matter (SP(GM)), and temporalis muscle (SP(MUS)) were then calculated. Contrast between tissues and MS lesions in the MR and derived images was then determined by measuring the signal-difference-to-noise ratio (dSNR) between tissues. Our new SP images provided better tissue contrast than the original MR, filtered MR, and PC images. Contrast improved between CSF and NAWM (from 19.5 to 56), CSF and GM (from 15 to 36), GM and NAWM (from 8 to 14), MS lesions and CSF (from 16 to 35), and between MS lesions and NAWM (from 24 to 47). (Maximum contrast in the original MR images compared to maximum contrast in the SP images.) The additional contrast in SP images may aid the quantification and analysis of lesion activity in MR exams of MS patients.

Adult↗
PubMed2001

Definition of the rheological glass transition temperature in association with the concept of iso-free-volume.

Small deformation dynamic oscillation was used to develop an index of physical significance for the rationalisation of the mechanical properties of high co-solute/biopolymer systems during vitrification. The index is based on the combined framework of Williams-Landel-Ferry equation with the free volume theory and is called the 'rheological glass transition temperature, T(g)' thus differentiating it from the empirical calorimetric T(g) used in thermal analysis. The rheological T(g) is located at the conjunction of two distinct molecular processes, namely: free-volume effects in the glass transition region and the predictions of the reaction-rate theory in the glassy state. The method of reduced variables was used to shift the mechanical spectra of shear moduli to composite curves. The temperature dependence of shift factors for all materials was identical provided that they were normalised at suitably different reference temperatures, which reflect iso-free-volume states. The treatment makes free volume the overriding parameter governing the mechanical relaxation times during vitrification of high co-solute/biopolymer systems regardless of physicochemical characteristics. We believe that potential applications resulting from this fundamental work are numerous for the food and pharmaceutical industries.

Biophysical Phenomena↗
PubMed2001

FTIR microspectroscopy study of composition fluctuations in extruded amylopectin-gelatin blends.

The spatial variation in the composition of nonexpanded biopolymer blends prepared by extrusion of mixtures of gelatin with either native or pregelatinized waxy maize starch was studied using a 30-microm aperture FTIR microspectroscopy technique. The ratio of the areas of the "saccharide" bands (953-1180 cm(-1)) and the amide I and II bands (1483-1750 cm(-1)) was used to monitor the relative distributions of the two components of the blend. Two calibration methods were used to obtain amylopectin concentration values from the ratios of the IR bands. The results suggested a high degree of heterogeneity in these blends, despite the thorough mixing expected by twin-screw extrusion processing. The concentration fluctuations were greater for the blends produced by extruding gelatin and native waxy maize starch mixtures. This was in agreement with the reduced degree of conversion of the starch granules when extruded in the presence of gelatin. The FTIR 2-dimensional maps obtained suggested that in the blends produced from either native or pregelatinized starch at all concentrations studied (25/75, 50/50, and 75/25 amylopectin/gelatin) the gelatin constituted the continuous phase. The effect of the spatial resolution on the FTIR microspectroscopy results was considered and the proposed interpretation was verified by the use of polarized light microscopy and FTIR microspectroscopy acquired at higher spatial resolution (10 microm).

Amylopectin↗
PubMed2001

A semi-automatic technique for measurement of arterial wall from black blood MRI.

Black blood magnetic resonance imaging (MRI) has become a popular technique for imaging the artery wall in vivo. Its noninvasiveness and high resolution make it ideal for studying the progression of early atherosclerosis in normal volunteers or asymptomatic patients with mild disease. However, the operator variability inherent in the manual measurement of vessel wall area from MR images hinders the reliable detection of relatively small changes in the artery wall over time. In this paper we present a semi-automatic method for segmenting the inner and outer boundary of the artery wall, and evaluate its operator variability using analysis of variance (ANOVA). In our approach, a discrete dynamic contour is approximately initialized by an operator, deformed to the inner boundary, dilated, and then deformed to the outer boundary. A group of four operators performed repeated measurements on 12 images from normal human subjects using both our semiautomatic technique and a manual approach. Results from the ANOVA indicate that the inter-operator standard error of measurement (SEM) of total wall area decreased from 3.254 mm2 (manual) to 1.293 mm2 (semi-automatic), and the intra-operator SEM decreased from 3.005 mm2 to 0.958 mm2. Operator reliability coefficients increased from less than 69% to more than 91% (inter-operator) and 95% (intra-operator). The minimum detectable change in wall area improved from more than 8.32 mm2 (intra-operator, manual) to less than 3.59 mm2 (inter-operator, semi-automatic), suggesting that it is better to have multiple operators measure wall area with our semi-automatic technique than to have a single operator make repeated measurements manually. Similar improvements in wall thickness and lumen radius measurements were also recorded. Since the semi-automatic technique has effectively ruled out the effect of the operator on these measurements, it may be possible to use such techniques to expand prospective studies of atherogenesis to multiple centers so as to increase access to real patient data without sacrificing reliability.

Adult↗
PubMed2001

RNA binding domain of telomerase reverse transcriptase.

Telomerase is a ribonucleoprotein reverse transcriptase that extends the ends of chromosomes. The two telomerase subunits essential for catalysis in vitro are the telomerase reverse transcriptase (TERT) and the telomerase RNA. Using truncations and site-specific mutations, we identified sequence elements of TERT and telomerase RNA required for catalytic activity and protein-RNA interaction for Tetrahymena thermophila telomerase. We found that the TERT amino and carboxyl termini, although evolutionarily poorly conserved, are nonetheless important for catalytic activity. In contrast, high-affinity telomerase RNA binding requires only a small region in the amino terminus of TERT. Surprisingly, the TERT region necessary and sufficient for telomerase RNA binding is completely separable from the reverse transcriptase motifs. The minimal Tetrahymena TERT RNA binding domain contains two sequence motifs with ciliate-specific conservation and one TERT motif with conservation across all species. With human TERT, we demonstrate that a similar region within the TERT amino terminus is essential for human telomerase RNA binding as well. Finally, we defined the Tetrahymena telomerase RNA sequences that are essential for TERT interaction. We found that a four-nucleotide region 5' of the template is critical for TERT binding and that the 5' end of telomerase RNA is sufficient for TERT binding. Our results reveal at least one evolutionarily conserved molecular mechanism by which the telomerase reverse transcriptase is functionally specialized for obligate use of an internal RNA template.

Animals↗
PubMed2001

Effects of chronic central nervous system administration of agouti-related protein in pair-fed animals.

The melanocortin receptor (MC3-R and MC4-R) antagonist, agouti-related protein (AGRP), is a potent stimulant of food intake. We examined the effect of chronic intracerebroventricular (ICV) AGRP treatment on energy metabolism and pituitary function in ad libitum fed rats and rats administered AGRP and then pair-fed to a saline control group. Chronic ICV AGRP (83-132) administration (1 nmol/day for 7 days) significantly increased food intake and body weight in ad libitum fed animals compared with saline-treated controls (body weight on day 7: 272 +/- 6 [saline] vs. 319 +/- 8 g [AGRP ad libitum fed]; P < 0.001). A significant increase in the epididymal fat pad weight, interscapular brown adipose tissue (BAT) weight, and plasma leptin was also observed in the ad libitum fed group. In the AGRP pair-fed group, a significant increase in the epididymal fat pad weight, BAT weight, and plasma leptin was again observed, suggesting that AGRP caused metabolic changes independent of increased food intake. BAT uncoupling protein 1 (UCP-1) content was significantly decreased compared with saline controls in both the AGRP ad libitum fed (21 +/- 8% of saline control; P < 0.01) and AGRP pair-fed groups (24 +/- 7% of saline control; P < 0.01). Plasma thyroid-stimulating hormone (TSH) was significantly suppressed compared with saline controls in both the AGRP ad libitum fed and AGRP pair-fed groups (3.5 +/- 0.3 [saline] vs. 2.7 +/- 0.4 [AGRP ad libitum fed] vs. 2.1 +/- 0.2 ng/ml [AGRP pair-fed]; P < 0.01). This study demonstrates that independent of its orexigenic effects, chronic AGRP treatment decreased BAT UCP-1, suppressed plasma TSH, and increased fat mass and plasma leptin, suggesting that it may play a role in energy expenditure.

Adipose Tissue↗
PubMed2001

The effect of injection speed on the perception of intramuscular injection pain. A clinical update.

Injections are frequently administered by occupational health nurses in worksite health promotion programs. The purpose of this study was to examine the effect of varying injection speed on the perception of pain. Fifty workers were given intramuscular (i.m.) hepatitis B vaccine at injection speeds of 10 and 30 seconds per cubic centimeter (s/cc). The perception of pain was measured on a visual analogue scale and reported post-injection at three different time intervals. The results showed that no difference in pain was perceived by participants between the two injection speeds. Results also revealed that women consistently had higher mean pain scores than men and significantly more pain at the 0 hour measurement of the 10 s/cc injection. While the results of this study indicate no need to administer an i.m. injection slower than 10 s/cc, occupational health nurses will need to consider gender differences in pain perception when administering injections.

Adult↗
PubMed2000

Isothermal and non-isothermal crystallization in amorphous sucrose and lactose at low moisture contents.

Differential scanning calorimetry has been used in isothermal and non-isothermal modes to provide information on the crystallization of sucrose and lactose at low water contents. Using approaches previously applied to polymer crystallization an attempt has been made to combine the isothermal and non-isothermal data into a single curve. This is achieved by the use of appropriate shift factors in the time and temperature domains. This was successful for sucrose but not for lactose. It was suggested that this was because lactose crystallizes into multiple forms whereas sucrose crystallizes in a single form.

Calorimetry, Differential Scanning↗
PubMed2000

Viscoelastic properties of pectin--co-solute mixtures at iso-free-volume states.

Small-deformation oscillatory measurements were performed on pectin-sucrose-glucose syrup systems at a total level of solids of 81%, with the polysaccharide content being fixed at levels of industrial use (1%). The experimental temperature range was between 50 and - 50 degrees C. Analysis of the temperature dependence of viscoelastic processes by the equation of Williams, Landel, and Ferry provides values of fractional free volume for the temperatures covering the glass transition region. The shift factors used in the conversion of mechanical spectra into master curves were normalised at suitably different temperatures so that their temperature dependence becomes coincident. The treatment implies an iso-free-volume state and relates to changes in the monomeric friction coefficient with increasing levels of intermolecular interactions in the mixture. A free-volume related glass transition temperature was defined and manipulated markedly by introducing pectin of variable degrees of esterification to the sucrose-glucose syrup system.

Chemical Phenomena↗
PubMed2000

The retrogradation of waxy maize starch extrudates: effects of storage temperature and water content.

The effects of water content and storage temperature on the kinetics of the retrogradation of nonexpanded waxy maize starch extrudates were studied using (1)H pulsed NMR and wide-angle X-ray diffraction. The increase in crystallinity observed by XRD was accompanied by a decrease in the relaxation times of the solid-like component of the NMR free induction and the spin-echo decays, and an increase in the contribution of the solid-like component to the total signal. The dependence of the rate of starch retrogradation on the storage temperature showed the typical "bell-shaped" behavior, which was successfully modeled using the Lauritzen-Hoffman theory of crystallization of chain-folded polymers. This theory was extended to model the effect of water content on the rate of isothermal crystallization by exploiting the ten-Brinke and Karasz, and the Flory equations to describe the dependence of the glass-transition and the melting temperatures on water content.

Biopolymers↗
PubMed2000

Magnetization transfer and multicomponent T2 relaxation measurements with histopathologic correlation in an experimental model of MS.

Magnetization transfer and multicomponent T2 imaging techniques were implemented to study guinea pig in vivo. A chronic-progressive model of experimental allergic encephalomyelitis (EAE) was produced, and the inflammatory component of the disease was manipulated using antibodies against integrin. The magnetization transfer ratio (MTR) and T2 relaxation properties were measured in normal-appearing white matter (NAWM) with histological comparisons. Significant reductions in both the mean MTR and the myelin water percentage were measured in NAWM of EAE guinea pig brain. However, the MTR and myelin water percentage appear to measure different aspects of pathology in NAWM in EAE. Reductions in the MTR were prevented or reversed with suppression of inflammation. However, modulation of inflammatory activity was not reflected in the measurement of the myelin water percentage. Since the amount of myelin is not expected to vary with inflammatory-related changes, these observations support our hypothesis that the MTR is sensitive to physiological changes to myelin induced by inflammation, while the short T2 component is a more specific indicator of myelin content in tissue. Pathologic features other than demyelination may be important in the determination of the MTR.

Animals↗
PubMed2000

Human telomerase activation requires two independent interactions between telomerase RNA and telomerase reverse transcriptase.

Inhibition or activation of the reverse transcriptase telomerase can profoundly affect the proliferative capacity of normal cells and cancers. Here, we elucidate structural requirements for function of the essential RNA component of human telomerase, hTR. Two motifs within the independently stable H/ACA domain of hTR are required for accumulation of the mature RNA in vivo. However, these motifs can be substituted by a heterologous H/ACA family RNA. Two additional hTR elements are required both in vivo and in vitro for telomerase catalytic activity. Surprisingly, each of these elements independently binds to the telomerase reverse transcriptase. Our results establish fundamental differences between vertebrate and ciliate telomerase ribonucleoprotein architectures and also suggest strategies for the pharmaceutical development of telomerase-based anticancer therapies.

Base Sequence↗