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Biomedical subjects

K Parsons

Publications and source records attributed to K Parsons.

At least 19 recordsLinked to original sources

Analysis of T-cell receptor BV gene sequences in cattle reveals extensive duplication within the BV9 and BV20 subgroups.

We investigated the repertoire of functional T-cell receptor beta-chain variable genes (TRBV genes) in cattle by analysing the nucleotide sequences and predicted amino acid sequences of a set of cDNA clones isolated from lymph node T cells. Thirty-nine distinct TRBV sequences were identified, bringing the total number of recognised bovine TRBV gene segments to more than 40. Sixteen TRBV subgroups were defined based on their sequence homology to each other and to human TRBV genes. All of the main phylogenetic lineages of BV gene subgroups described in humans and mice were represented. Eight of the subgroups were found to contain more than one member. The most striking feature of the results was the large number of sequences (more than half of the sequenced clones) in the BV9 and BV20 subgroups, which were found to contain 12 and 8 distinct sequences, respectively. In contrast, the corresponding human TRBV subfamilies contain a single member. The results indicate that, as in humans, there has been extensive gene duplication within the TRBV locus during evolution. However, duplication of different BV subgroups in cattle has resulted in a TRBV gene repertoire distinct from that found in other species.

Amino Acid Sequence↗

Analysis of the repertoire of cattle CD4(+) T cells reactive with bovine viral diarrhoea virus.

Cell-mediated immunity and CD4(+) cells in particular are important for the resolution of acute infection with non-cytopathic bovine viral diarrhoea virus (BVDV). CD4(+) T cells were shown to recognise virus-infected and non-infectious-protein-pulsed APCs, whereas CD8(+) T cells recognised only virus-infected APCs. T cell recognition was strain cross-reactive and MHC-restricted. Using native and recombinant antigens, we identified the structural glycoprotein E2 and the non-structural protein NS3 as dominant CD4(+) T cell determinants. The repertoire of CD4(+) T cell responses to E2 and NS3 was examined using inbred, homozygous cattle and overlapping synthetic peptides. The repertoire was biased toward conserved regions of NS3 and excluded the hypervariable regions of E2. The number of peptides that were recognised varied between animals but patterns could be distinguished in those animals that shared the same DRB3(*) allele. Of particular interest were: (i) a determinant that was recognised in the context of both DRB3(*) alleles (i.e. DRB3(*)2002 and DRB3(*)0701), (ii) two determinants that were juxtaposed to B cell sites, and (iii) a determinant that had structural analogy with a NS3 epitope previously described for the closely related hepatitis C virus. The minimum stimulatory sequence of the latter, NS3(397-414), was located to residues NS3(400-410).

Amino Acid Sequence↗

Assessment of the risk of heat disorders encountered during work in hot conditions.

OBJECTIVE: To co-ordinate the work of the main European research teams in the field of thermal factors in order to develop and improve significantly the methods presently available for assessing the risks of heat disorders encountered during work in hot conditions. METHOD: Each item from the required sweat rate model was reviewed on the basis of the most recent literature. A database with 1,113 laboratory and field experiments, covering the whole range of hot working conditions, was assembled and used for the validation. RESULTS: Influence of clothing ensemble on heat exchange: methods and formulas were developed that take into account the dynamic effects associated with forced convection and the pumping effect associated with body movements and exercise. Prediction of the average skin temperature: the model used in the required sweat rate standard ISO 7933 was extended to cover more severe conditions with high radiation and high humidity and different clothing and take into account the rectal temperature for the prediction of the skin temperature. Criteria for estimating acceptable exposure times in hot work environments: criteria were reviewed and updated concerning the maximum increase in core temperature and the acceptable water loss, for acclimatised and nonacclimatised subjects. These limits are intended to protect 95% of the population. Measuring strategy: a strategy was developed to assess the risks in any working situation with varying conditions of climate, metabolic rate or clothing. A detailed methodology was developed in three stages: an "observation" method for the recognition of the conditions that might lead to thermal stress; an "analysis" method for evaluating the problem and optimising the solutions; and an "expert" method for in-depth analysis of the working situation when needed. VALIDATION: the different results were used to prepare a revision of the interpretation procedure proposed in the ISO standard 7933. We validated the modified approaches using the database. This involved the whole range of conditions for which the model was extended, namely conditions with high and low radiation, humidity and air velocity as well as fluctuating conditions. Based on these results, the predicted heat strain model was developed: it is presently proposed as an ISO and CEN standard.

Biomechanical Phenomena↗

Development and validation of the predicted heat strain model.

Eight laboratories participated in a concerted research project on the assessment of hot working conditions. The objectives were, among others, to co-ordinate the work of the main European research teams in the field of thermal factors and to improve the methods available to assess the risks of heat disorders at the workplace, and in particular the "Required Sweat Rate" model as presented in International Standard ISO 7933 Standard (1989). The scientific bases of this standard were thoroughly reviewed and a revised model, called "Predicted Heat Strain" (PHS), was developed. This model was then used to predict the minute by minute sweat rates and rectal temperatures during 909 laboratory and field experiments collected from the partners. The Pearson correlation coefficients between observed and predicted values were equal to 0.76 and 0.66 for laboratory experiments and 0.74 and 0.59 for field experiments, respectively, for the sweat rates and the rectal temperatures. The change in sweat rate with time was predicted more accurately by the PHS model than by the required sweat rate model. This suggests that the PHS model would provide an improved basis upon which to determine allowable exposure times from the predicted heat strain in terms of dehydration and increased core temperature.

Algorithms↗

Protein kinase C isoenzyme patterns characteristically modulated in early prostate cancer.

Expression of protein kinase C (PKC) isoenzymes -alpha, -beta, -delta, -epsilon, -gamma, -iota, -lambda, -mu, -theta, and -zeta, and of their common receptor for activated C-kinase (RACK)-1, was determined immunohistochemically using specific antibodies in formalin-fixed and paraffin-embedded specimens of early prostatic adenocarcinomas (n = 23) obtained at radical prostatectomy. Expression of each isoenzyme by malignant tissues was compared with nonneoplastic prostate tissues removed at radical cystectomy (n = 10). The most significant findings were decreased PKC-beta expression in early neoplasia when compared to benign epithelium (P < 0.0001), together with a reciprocal increase in expression of PKC-epsilon (P < 0.0001). Detectable levels of PKC-alpha and PKC-zeta were also significantly increased in the cancers (P = 0.045 and P = 0.015 respectively) but did not correlate with either PKC-beta or PKC-epsilon for individual cases. Alterations in the levels of the four PKC isoenzymes occurred specifically and consistently during the genesis and progression of human prostate cancer. PKC-delta, -gamma, and -theta were not expressed in the epithelium of either the benign prostates or the cancers. Levels of expression for PKC-A, -iota, -mu, and RACK-1 were not significantly different between the benign and malignant groups. Although changes in PKC isoenzyme expression may assist in explaining an altered balance between proliferation and apoptosis, it is likely that changes in activity or concentrations of these isoenzymes exert important modulating influences on particular pathways regulating cellular homeostasis. The findings of this study raise an exciting possibility of novel therapeutic intervention to regulate homeostatic mechanisms controlling proliferation and/or apoptosis, including expression of the p170 drug-resistance glycoprotein, intracellular Ca2+ concentrations, and enhanced cellular mobility resulting in the metastatic dissemination of human prostate cancer cells. Attenuation of PKC-beta expression is currently being assessed as a reliable objective adjunct to morphological appearance for the diagnosis of early progressive neoplasia in human prostatic tissues.

Disease Progression↗

Clothing convective heat exchange--proposal for improved prediction in standards and models.

Convection is an important determinant for both sensible and evaporative heat exchange. Heat transfer by convection for normal boundary conditions is readily described by simple power functions. Clothing affects convection in various ways and existing characterisation of clothing by its static insulation values produces inaccurate prediction of sensible heat exchange, eventually leading to erroneous risk assessment. The present paper reviews various methods for evaluation of clothing convective (sensible) heat exchange. Based on available data, two equations are proposed for determination of the reduction of the total insulation values obtained under static, still wind conditions as a consequence of wind and walking effects. The equations apply from 0 to 1.84 clo, from 0.2 to 3 m/s and for walking speeds up to 1.2 m/s. The equations are incorporated in ISO 7933 to provide a more realistic and accurate prediction of sensible heat transfer through clothing.

Bias↗

Transurethral microwave thermotherapy in the treatment of benign prostatic hyperplasia: results obtained with the Urologix T3 device.

The objective of this study was to assess the efficacy and safety of a new transurethral microwave thermotherapy device, T3, in the treatment of symptomatic benign prostatic hyperplasia. A total of 155 patients were recruited at 3 sites and treated using an identical protocol. The mean AUA symptom score decreased by 58% at 12 months, by 61% at 24 months and by 56% at 36 months. The increase in mean peak flow rates at these time points was 3.9 (47%), 3.4 (44%) and 5.1 ml/s (67%), respectively. Adverse events were minor and the patients' satisfaction with treatment was high. Transurethral microwave thermotherapy with the T3 device provides a safe, effective treatment for symptomatic benign prostatic hyperplasia.

Aged↗

A novel transurethral microwave thermal ablation system to treat benign prostatic hyperplasia: results of a prospective multicenter clinical trial.

PURPOSE: We evaluated the efficacy, safety and impact on quality of life of a newly designed microwave thermal ablation system in patients with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Microwave thermal ablation was administered to 154 BPH patients at 3 centers in Canada and the United Kingdom during a single 1 to 2-hour office or clinic procedure without general or regional anesthesia and without need for potent medications necessitating intensive patient monitoring. Various measures of symptoms, voiding function and patient quality of life were assessed at baseline, 6 weeks, and-3, 6, 9 and 12 months after treatment. RESULTS: Mean American Urological Association symptom score 12 months after treatment (8.8, 95% confidence interval 7.7 to 10.0) was significantly lower (p < 0.05) by 56% than that at baseline (20.1, 95% confidence interval 19.1 to 21.0). The incidence of mild symptoms increased from 0 to 57%, while that of severe symptoms decreased from 49 to 8%. There was a significant increase (p < 0.05) in peak flow rate of 45% from 9.3 ml. per second (95% confidence interval 8.8 to 9.7) at baseline to 13.4 ml. per second (95% confidence interval 12.5 to 14.4) at 12 months. Similar symptomatic and urodynamic improvements occurred in all prostate volume categories. Convalescence was rapid after treatment with little or no need for home bed rest or restriction of usual activities. Patients expressed a high level of satisfaction with treatment and found the prostate symptoms to be significantly more tolerable. Adverse events were infrequent, transient and readily managed. CONCLUSIONS: Microwave thermal ablation proved to be safe and effective for treatment of BPH with a significant positive impact on patient quality of life.

Aged↗

Effects of glucose deprivation on the contractile response of the rabbit bladder to repetitive stimulation.

The urinary bladder requires an adequate energy supply to maintain contractile function. The primary metabolic fuel is glucose. Through glycolysis and oxidative phosphorylation, high energy phosphates are generated, which in turn supply the metabolic energy for the contractile activities of the urinary bladder. The aim of this study was to determine the effects of glucose deprivation and recovery from glucose deprivation on the phasic and tonic components of the contractile responses of rabbit bladder strips to field stimulation, bethanechol, and KCl. The results can be summarized as follow: In response to glucose deprivation, (1) the tonic responses to field stimulation, bethanechol, and KCl all decreased at a significantly greater rate than the phasic responses; (2) the phasic and tonic responses to field stimulation were both reduced to less than 10% of control within 70 minutes of initiating glucose deprivation; (3) the tonic responses to bethanechol and KCI were reduced to approximately 10% of control within 180 minutes whereas the phasic responses remained stable at 40 and 30%, respectively; and (4) glucose replacement stimulated a rapid and nearly complete recovery of the phasic and tonic components of the responses to field stimulation, bethanechol, and KCI. These results indicate that the tonic responses to all forms of stimulation are more sensitive to glucose deprivation than the phasic responses.

Animals↗

Effects of partial outlet obstruction on bladder-strip sensitivity to glucose deprivation: an in vitro study in the rat.

Partial outlet obstruction has been shown to result in contractile and metabolic dysfunctions. Specifically, there is a greater reduction in the response to field stimulation (FS) in comparison with the responses to bethanechol and KCl, a greater reduction in the tonic response to stimulation in comparison with the phasic response, and a reduction in oxidative metabolism of glucose accompanied by an increase in the glycolytic metabolism of glucose. The specific aim of the current study was to correlate the effects of partial outlet obstruction on the contractile responses of isolated strips of bladder smooth muscle to repetitive stimulation in the presence and absence of glucose. Adult male Sprague-Dawley rats were subjected to partial outlet obstruction by the surgical placement of silk ligatures around the urethra. After 2 weeks, each rate was anesthetized, the bladder was excised, and isolated strip studies were performed. These studies demonstrated that the maximal phasic response to FS was significantly decreased in the obstructed strips as compared with controls, with no difference being noted for responses to bethanechol or KCl; the tonic responses to all forms of stimulation were significantly decreased after obstruction, with the tonic response to FS being decreased to a greater degree than were the tonic responses to bethanechol and KCl; and in the absence of glucose, the tonic responses of control strips to all forms of stimulation were reduced to a greater degree than were the phasic responses. These studies demonstrate that the tonic response to FS is extremely sensitive to fatigue induced by repetitive stimulation.

Analysis of Variance↗

Cerebellar granule neurons develop elevated calcium responses when treated with interleukin-6 in culture.

In humans, elevated levels of cytokines are associated with several diseases (including HIV infection and Down Syndrome) that result in developmental abnormalities. Overexpression of interleukin-6 (IL-6) in the central nervous system has been shown to cause extensive neuronal abnormality in mice that becomes more evident with maturation. However, it is difficult to separate direct effects of IL-6 on the developing neurons of an intact animal from indirect effects involving effects on other cell types that possess cytokine receptors, such as microglia and astrocytes. We have found that IL-6 treatment of rat cerebellar granule neurons developing in the absence of other cell types in culture results in the persistence of large, depolarization or neurotransmitter-induced calcium transients, that are normally observed only in immature neurons. The cause of this appears to be the persistence of a calcium-induced calcium release (CICR) component of the calcium response to stimulation. This basic abnormality in neuronal development may contribute to the developmental abnormalities associated with human syndromes that involve elevated cytokine levels.

Age Factors↗

Primary explants of human uroepithelium show an unusual response to low-dose irradiation with cobalt-60 gamma rays.

Recent results using very low doses of radiation have suggested that there is a hypersensitive region where cultures show an enhanced level of cell killing leading to a non-monotonic survival curve. This effect has been observed at doses below 2 Gy in mammalian systems and at much higher doses in insect cells. In this paper we report observation of the effect in primary human uroepithelial cell cultures. The effect was measured using a postirradiation proliferation assay where irradiated explants of standard size were allowed to proliferate for 14 days after exposure to 60Co gamma irradiation. By 14 days the majority of cultures derived from explants irradiated with 2-5 Gy showed little evidence of growth inhibition and cell numbers approached or even exceeded those obtained in the controls. There was, however, a significant reduction in cell number and growth rate in all cultures exposed to doses lower than 1 Gy. Oncoprotein (p53, c-myc, bcl-2, p21 ras) and EGFR expression were also measured in these cultures and were significantly increased. Morphological evidence of apoptosis was present in all irradiated cultures at 4 h after exposure, but this persisted for longer periods in cultures exposed to low doses.

Cell Survival↗

Assessment of cartilage volume in the femorotibial joint with magnetic resonance imaging and 3D computer reconstruction.

OBJECTIVE: Our goal was the development of an accurate and objective technique to depict and quantitate articular cartilage using magnetic resonance imaging (MRI) and 3D data processing. METHODS: A method of 3D image analysis has been developed that provides a noninvasive technique of measuring cartilage volume from standard diagnostic MR images. RESULTS: Using a computer workstation, cartilage from Fast Field Echo (FFE) MR images was reconstructed into 3 dimensions (3D). The accuracy and reproducibility of both thickness and volume measurements obtained from the existing computer software was tested using calibration test objects. We describe the sources of error we encountered when attempting to quantitate cartilage using the existing computer software, the methods developed to reduce these errors, and a preliminary cartilage volume study using healthy human volunteers. CONCLUSION: We have identified errors involved in attempting cartilage volume estimations using the existing 3D computer software and have developed a data processing technique that minimizes these errors. With these objective data processing techniques we have improved the reproducibility of the technique to +/- 10-15% error. This modified technique provides a promising new method for viewing and quantifying cartilage volume from standard diagnostic MR images.

Animals↗

Analysis of the gamma/delta T cell restricted antigen WC1.

The nine antibodies (mAbs) which clustered with the standard WC1 mAb CC15 in temporary cluster TC22 were analysed by immunoprecipitation, flow cytometry and immunohistology. Two forms of the molecule, with molecular weights of 205 and 215 kDa, were identified by immunoprecipitation and SDS-PAGE, the expression of which correlated with subclusters generated by flow cytometric analysis. Immunohistological data, however, did not reveal any tissue specific distribution. We propose the existence of at least two isoforms of WC1 which may prove to identify subpopulations of CD2- CD4- CD8- gamma/delta T cells.

Animals↗