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Biomedical subjects

J S Fleming

Publications and source records attributed to J S Fleming.

At least 37 records · Page 2Linked to original sources
PubMed1999

Evidence for a neural inhibitory factor which downregulates fetal-type acetylcholine receptor expression in skeletal muscle cell lines.

Nerve-evoked muscle depolarisation plays an important role in the downregulation of extrasynaptic AChRs which accompanies the increase in synaptic AChR expression at the neuromuscular junction during embryonic development. However, additional mechanisms may be involved in the AChR downregulation. This study provides evidence for a neurotrophic factor present in adult and embryonic chick neural extracts which downregulates fetal-type AChR density independently of depolarisation. Treatment of skeletal muscle cell lines with crude neural extracts decreased AChR density up to 50%, as measured by changes in 125I-alpha-bungarotoxin binding levels. Decreases in membrane-bound AChR density were accompanied by a decrease in the size of the intracellular AChR pool; RT-PCR analysis demonstrated that extract treatment also induced a decrease in gamma-subunit mRNA expression. These studies demonstrate that crude neural extracts contain a factor which may account for the activity-independent regulatory mechanism previously proposed to operate in concert with activity-dependent mechanisms to downregulate fetal-type AChR expression.

Animals↗
PubMed1999

A technique for manual definition of an irregular volume of interest in single photon emission computed tomography.

A technique is described for manually outlining a volume of interest (VOI) in a three-dimensional SPECT dataset. Regions of interest (ROIs) are drawn on three orthogonal maximum intensity projections. Image masks based on these ROIs are backprojected through the image volume and the resultant 3D dataset is segmented to produce the VOI. The technique has been successfully applied in the exclusion of unwanted areas of activity adjacent to the brain when segmenting the organ in SPECT imaging using 99mTc HMPAO. An example of its use for segmentation in tumour imaging is also presented. The technique is of value for applications involving semi-automatic VOI definition in SPECT.

3-Iodobenzylguanidine↗
PubMed1999

Semi-automated tabulation of the 3D topology and morphology of branching networks using CT: application to the airway tree.

Detailed information on biological branching networks (optical nerves, airways or blood vessels) is often required to improve the analysis of 3D medical imaging data. A semi-automated algorithm has been developed to obtain the full 3D topology and dimensions (direction cosine, length, diameter, branching and gravity angles) of branching networks using their CT images. It has been tested using CT images of a simple Perspex branching network and applied to the CT images of a human cast of the airway tree. The morphology and topology of the computer derived network were compared with the manually measured dimensions. Good agreement was found. The airways dimensions also compared well with previous values quoted in literature. This algorithm can provide complete data set analysis much more quickly than manual measurements. Its use is limited by the CT resolution which means that very small branches are not visible. New data are presented on the branching angles of the airway tree.

Algorithms↗
PubMed1999

Clusterin is expressed in the anterior and intermediate lobes, but not in the posterior pituitary of sheep.

We have examined the expression of the ovine clusterin gene in the sheep pituitary gland, with the aim of determining its site of synthesis in this tissue. Northern blotting analysis of extracted polyadenylated RNA, using a (32)P-labelled rat clusterin cDNA probe, detected the greatest amounts of clusterin mRNA in the anterior part of dissected pituitary glands. In situ hybridisation studies showed clusterin mRNA in anterior and intermediate pituitary cells, with lower amounts in vascular endothelium and posterior pituicytes. Clusterin protein, detected by immunohistochemistry, was observed in some single secretory cells, within the capillary lumen and in cells around capillaries in the anterior and intermediate lobes, but no immunoreactivity was observed in posterior pituitary tissue. The pattern of clusterin expression in anterior and intermediate pituitary cells suggests possible roles for the protein in secretory cell turnover and/or hormone secretion or lipid uptake. Clusterin does not appear to be involved in ovine posterior pituitary hormone neurosecretion.

Animals↗
PubMed1999

A comparison of deconvolution and the Patlak-Rutland plot in renography analysis.

UNLABELLED: Deconvolution and the Patlak-Rutland plot are two of the most commonly used methods for analyzing dynamic radionuclide renography. Both methods allow estimation of absolute and relative renal uptake of radiopharmaceutical and of its rate of transit through the kidney. METHODS: A theoretical comparison of uptake assessment by both techniques is made and a mathematical derivation of the relationship between mean transit time (MTT) and renal outflow efficiency (ROE) is presented. The validity of these theoretical findings was tested in a series of 120 renograms obtained using 99mTc-mercaptoacetyltriglycine (MAG3). RESULTS: The estimates of renal uptake obtained are theoretically equivalent. The renogram measurements confirmed this, because there was no significant systematic difference in relative counts obtained by the two methods. Absolute counts were significantly higher for the deconvolution measurements, but only by 2.0%. The SDs of the differences between the two techniques, expressed as a percentage of the mean, were 1.7% and 5.4% for relative and absolute counts, respectively. There was an inverse monotonic relationship between MTT and ROE. ROE evaluated at a particular time was shown to depend on absolute renal function. Measured values of MTT and ROE were consistent with the theoretical prediction. CONCLUSION: The two approaches to renogram analysis provide consistent parameters for both uptake and transit evaluation.

Adolescent↗
PubMed1998

A rule based method for context sensitive threshold segmentation in SPECT using simulation.

Robust techniques for automatic or semi-automatic segmentation of objects in single photon emission computed tomography (SPECT) are still the subject of development. This paper describes a threshold based method which uses empirical rules derived from analysis of computer simulated images of a large number of objects. The use of simulation allowed the factors affecting the threshold which correctly segmented objects to be investigated systematically. Rules could then be derived from these data to define the threshold in any particular context. The technique operated iteratively and calculated local context sensitive thresholds along radial profiles from the centre of gravity of the object. It was evaluated in a further series of simulated objects and in human studies, and compared to the use of a global fixed threshold. The method was capable of improving accuracy of segmentation and volume assessment compared to the global threshold technique. The improvements were greater for small volumes, shapes with large surface area to volume ratio, variable surrounding activity and non-uniform distributions. The method was applied successfully to simulated objects and human studies and is considered to be a significant advance on global fixed threshold techniques.

Algorithms↗
PubMed1998

Evaluation of the accuracy and precision of lung aerosol deposition measurements from planar radionuclide imaging using simulation.

Planar images of known, theoretical distributions of radioaerosol in the lung have been simulated using lung models derived from magnetic resonance studies on human subjects. Total lung activity was evaluated from the simulated images together with the absolute penetration index (PI) and a relative value expressed as a fraction of that in a simulated ventilation image. The accuracy and precision of these measurements were calculated by comparison with the true values used in the simulation. Total activity was assessed with systematic errors within 5% and precision within 6.5%. Measured PIs varied only slowly with true PI and inter-model variation masked changes between measurements on the different distributions. The relative PI reduced inter-model variation and provided significant differences between all the distributions. PI was significantly affected by misalignment of the lung region of interest. The conducting airways deposition fraction (CADF) used in the simulation correlated linearly with the fractional activity in a central lung region, allowing CADF to be estimated with a precision of 21%.

Aerosols↗
PubMed1998

UK audit of relative renal function measurement using DMSA scintigraphy.

A variety of software is used to determine quantitative parameters from radionuclide imaging procedures. Knowledge of the variability of parameter values found in different hospitals is an important aspect of clinical audit of these techniques. This study investigated the variation in relative renal function measurement from static DMSA scintigraphy in the UK. Ten studies representing a range of ages and relative function values were distributed in digital form to 100 hospitals with the assistance of the gamma camera computer suppliers and regional audit coordinators. The studies were analysed at each participating hospital and details of the different techniques and computer systems used were documented. The median value of relative percentage function was assessed for each of the studies. Methods varied in terms of the view used for analysis (54% geometric mean, 46% posterior), the type of background subtraction (single region 32%, separate regions 60%, none 8%) and the definition of the renal regions of interest (73% manual, 27% semi-automatic). Eighty-eight percent of results were within two percentage points of the study median and 98% within five percentage points. There were statistically significant differences observed in the results arising from the view used for the analysis and the background subtraction protocol. The results indicate that relative renal function assessment from static DMSA scintigraphy in the UK is essentially a reliable procedure, although improvements could be made by standardizing the technique used.

Adult↗
PubMed1998

Supercomputer description of human lung morphology for imaging analysis.

A supercomputer code that describes the three-dimensional branching structure of the human lung has been developed. The algorithm was written for the Cray C94. In our simulations, the human lung was divided into a matrix containing discrete volumes (voxels) so as to be compatible with analyses of SPECT images. The matrix has 3840 voxels. The matrix can be segmented into transverse, sagittal and coronal layers analogous to human subject examinations. The compositions of individual voxels were identified by the type and respective number of airways present. The code provides a mapping of the spatial positions of the almost 17 million airways in human lungs and unambiguously assigns each airway to a voxel. Thus, the clinician and research scientist in the medical arena have a powerful new tool to be used in imaging analyses. The code was designed to be integrated into diverse applications, including the interpretation of SPECT images, the design of inhalation exposure experiments and the targeted delivery of inhaled pharmacologic drugs.

Computer Simulation↗
PubMed1998

Role of cognitively stimulating home environment in children's academic intrinsic motivation: a longitudinal study.

The short- and long-term, and direct and indirect, relations between cognitively stimulating home environment and academic intrinsic motivation were investigated in a longitudinal study from childhood through early adolescence. Structural equations modeling was used to test the hypothesis that home environment positively predicts academic intrinsic motivation over this period. It was also hypothesized that home environmental processes would positively predict motivation controlling for socioeconomic status (SES). When children were age 8, home environment (comprising both direct observations and parent report) and SES were measured. Academic intrinsic motivation was assessed at ages 9, 10, and 13. Results supported the hypotheses. Home environment had statistically positive and significant, direct and indirect paths to academic intrinsic motivation from childhood through early adolescence, indicating both short- and long-term effects across these ages. Moreover, home environment was significant above and beyond SES. The findings revealed that children whose homes had a greater emphasis on learning opportunities and activities were more academically intrinsically motivated.

Adolescent↗
PubMed1997

The effects of a duplication in the ovine growth hormone (GH) gene on GH expression in the pituitaries of ram lambs from lean and fat-selected sheep lines.

Growth hormone (GH) gene expression was investigated in pituitaries of 14- to 15-month-old ram lambs from flocks selected for high (fat) or low (lean) back fat depth, which were also homozygous for a single GH gene allele, heterozygous or homozygous for a duplication in the GH gene. The pituitaries of lean sheep of all three GH genotypes were significantly heavier than those of fat sheep, but there were no pituitary weight differences between GH genotypes. No significant lean-fat selection line- or GH genotype-specific differences were measured in pituitary GH concentration. However there was a significant increase (P < 0.01) in the total pituitary content of GH in lean compared with fat animals and a significant interaction between GH genotype and lean-fat selection line (P < 0.05) was noted for GH content. No significant differences were measured in the relative concentration of GH mRNA, suggesting that the ratio of GH mRNA per mg total cellular RNA remained constant across lean-fat selection line and GH genotype. We conclude that the pituitary glands of Coopworth sheep selected for low backfat depth (lean) are bigger and have an increased GH content, but appear to contain similar concentrations of GH mRNA and immunoreactive GH as the pituitaries of fat sheep. The presence of the GH gene duplication in sheep has little measurable effect on the expression and storage of GH in the pituitary.

Alleles↗
PubMed1997

Expression of neurotrophin-3 in the growing velvet antler of the red deer Cervus elaphus.

Antlers are organs of bone which regenerate each year from the heads of male deer. In addition to bone, support tissues such as nerves also regenerate. Nerves must grow at up to 1 cm/day. The control of this rapid growth of nerves is unknown. We examined the relative expression of neurotrophin-3 (NT-3) mRNA in the different tissues of the growing antler tip and along the epidermal/dermal layer of the antler shaft of the red deer Cervus elaphus, using semi-quantitative reverse transcription-polymerase chain reaction. Expression in the tip was found to be highest in the epidermal/dermal layer and lowest in the cartilaginous layer in all developmental stages examined. These data correlate well with the density and pattern of innervation of these tissues. Along the epidermal/dermal layer of the antler shaft, expression was highest in the segments subjacent to the tip and lowest near the base, arguing for differences in the temporal expression of NT-3 in these segments. The expression of NT-3 in cells isolated from the different layers of 60-day antlers did not mirror that observed when whole tissues were used and may suggest regional specificity of NT-3 expression within antler tissues.

Amino Acid Sequence↗
PubMed1996

Xamoterol improves right ventricular systolic and diastolic function in pulmonary heart disease.

OBJECTIVE: Abnormal right ventricular function in patients with pulmonary heart disease (PHD) may contribute to their reduced exercise capacity. We have evaluated the effect of subacute dosing with xamoterol, a beta-1 adrenoreceptor partial agonist with inotropic properties, on right ventricular function in patients with PHD. PATIENTS: Twelve patients with advanced chronic obstructive pulmonary disease and clinical evidence of PHD received xamoterol 200 mg twice daily or placebo for 7 days in a randomised double-blind crossover study. Right heart krypton-81m radionuclide ventriculography was used to derive right ventricular ejection fraction (RVEF) both at rest and during submaximal exercise, and indices of right ventricular systolic and diastolic function at rest. RESULTS: During treatment with placebo, mean RVEF was 0.53 at rest and was unchanged during exercise. After xamoterol, mean RVEF was 0.55 at rest and increased to 0.59 during exercise. Xamoterol increased right ventricular peak ejection rate from 3.04 to 3.45 EDV.s-1 and mean early diastolic filling rate from 1.00 to 1.20 EDV.s-1. CONCLUSION: Subacute treatment with xamoterol in patients with PHD improves right ventricular systolic and diastolic function at rest and results in a favourable augmentation in right ventricular function during submaximal exercise.

Aged↗
PubMed1996

Evaluation of a technique for simulation of gamma camera images.

Simulation of the gamma camera imaging process has applications in radionuclide imaging in image formation, interpretation and evaluation. Current algorithms are hindered by the length of time taken to perform accurate simulation. In this study an algorithm is developed which uses a number of simplifying approximations to improve speed of operation: restriction of the extent of the primary and scatter point spread functions, coarse sampling of the PSFs in the direction perpendicular to the camera face and use of a circularly symmetric scatter function. The effect of these approximations is assessed qualitatively and quantitatively by comparing simulations with corresponding real measurements. The application of the technique to clinical images using magnetic resonance data is demonstrated. The results show that improvements in speed of about a factor of ten may be achieved at the expense of minimal loss of accuracy. The algorithm should prove useful in speeding up applications of simulation.

Algorithms↗
PubMed1996

Assessment of deposition of inhaled aerosol in the respiratory tract of man using three-dimensional multimodality imaging and mathematical modeling.

Multimodality medical imaging enables measurement of the three-dimensional spatial distribution of a radiolabeled aerosol within the lung. Using a conceptual spatial morphological model these data may be transformed to provide information on deposition per airway generation. This methodology has been used to study the intrapulmonary deposition patterns of two formulations of a metered dose inhaler and two nebulizers in control subjects. The nebulizer study has also been stimulated using a computer model of deposition. The comparison between derived experimental results and those from computer modeling shows areas of agreement, although there are also areas of discrepancy. The new methodology has considerable potential value in the fields of inhalation therapy and deposition modeling, although more detailed validation is still required.

Administration, Inhalation↗
PubMed1996

The pulmonary deposition of two aerosol preparations of nedocromil sodium delivered by MDI assessed by single photon emission computed tomography.

The pulmonary deposition and pharmacokinetics of fine and coarse radioactive aerosols of nedocromil sodium, of mass median aerodynamic diameters 16 microns and 24 microns respectively, delivered by metered dose inhaler (MDI) have been investigated. The corresponding geometric standard deviations of the particle size distributions were 5.32 and 3.93. Pulmonary deposition was assessed by both planar radionuclide scintigraphy and multi-modality three dimensional imaging using single photon emission computed tomography (SPECT) and x-ray computed tomography (CT). The three dimensional data were analysed by transformation to a hemispherical shape based on the fractional radial distance of each point in the lung from the centre to the corresponding extrapolated point on the periphery. This enabled parameters on the variation of both concentration of deposition and total amount deposited with penetration distance to be calculated. For both planar and SPECT data the central to peripheral concentration ratio (C/P ratio) was calculated. The three dimensional C/P ratio showed a median value (3.21) which was significantly higher than for the planar imaging (2.03) (p < 0.001). The parameter used to express the variation of total amount deposited was the median dose position. This showed that for both aerosols 50% of the dose was deposited at sites with a percentage central to peripheral distance of greater than 68%. There was a trend for total percentage of the fine aerosol in the lungs to be higher than for the coarse and for its deposition to be more peripheral. In addition the mean concentrations in blood were measured to be greater for the fine aerosol. However these differences were relatively small and none were individually statistically significant. The technique of combined SPECT and CT imaging was shown to be valuable in obtaining more accurate information on pulmonary distribution of inhaled aerosol deposition. The merits, limitations and potential applications of the technique are discussed.

Administration, Inhalation↗