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Biomedical subjects

M A Watson

Publications and source records attributed to M A Watson.

At least 19 recordsLinked to original sources
PubMed2006

Matrilin-2 expression distinguishes clinically relevant subsets of pilocytic astrocytoma.

Using whole genome expression microarray technology to discover clinically relevant biomarkers for pilocytic astrocytoma (PA), the authors identified matrilin-2 as a unique mRNA overexpressed in PA. Matrilin-2 protein expression was similarly elevated in the majority of sporadic PA, but in only one neurofibromatosis 1-associated PA with an unusually aggressive clinical phenotype. These results suggest that matrilin-2 may be a specific and clinically useful biomarker for discriminating between indolent and clinically aggressive PA.

Astrocytoma↗
PubMed2006

Determination of the pressure required to cause mitral valve failure.

A method has been developed for applying water pressure to a closed mitral valve on the side corresponding to the heart's left ventricle. The pressure is increased until fluid flows through the valve, i.e. until it fails. A specific dissection technique has been developed to produce a specimen with two annular rings, mitral annulus and papillary muscle annulus. Since the valve is maintained intact, with its leaflets attached to papillary muscles by the chordae tendineae, this method allows the effects of ruptured chordae and their surgical repair or replacement to be assessed in vitro. The chamber that holds the valve supports both the mitral annulus and papillary muscle annulus of the specimen. The mitral annulus is sutured onto rubber sheeting held in the chamber. The papillary muscle annulus is held in place by a Perspex support. The main part of the apparatus consists of a water pump connected through flexible tubing to the chamber that holds the valve in place. The pressure at failure is measured using a pressure transducer. Preliminary experiments demonstrate that anterior leaflet marginal chordae, but not strut chordae, are vital to valve function. Posterior leaflet chordae have been found to be important for valve competence.

Aortic Valve↗
PubMed2005

Stress avoidance in a common annual: reproductive timing is important for local adaptation and geographic distribution.

Adaptation to local environments may be an important determinant of species' geographic range. However, little is known about which traits contribute to adaptation or whether their further evolution would facilitate range expansion. In this study, we assessed the adaptive value of stress avoidance traits in the common annual Cocklebur (Xanthium strumarium) by performing a reciprocal transplant across a broad latitudinal gradient extending to the species' northern border. Populations were locally adapted and stress avoidance traits accounted for most fitness differences between populations. At the northern border where growing seasons are cooler and shorter, native populations had evolved to reproduce earlier than native populations in the lower latitude gardens. This clinal pattern in reproductive timing corresponded to a shift in selection from favouring later to earlier reproduction. Thus, earlier reproduction is an important adaptation to northern latitudes and constraint on the further evolution of this trait in marginal populations could potentially limit distribution.

Adaptation, Physiological↗
PubMed2005

Wire tension in the Ilizarov system: accuracy of the wire-tensioning device.

The Ilizarov fixator consists of tensioned wires that attach bone segments to a modular frame. The aim of this study was to establish the accuracy and precision of the wire-tensioning device supplied with the Ilizarov external fixation system. The device was used to tension a wire in direct opposition to a calibrated load cell. Five subjects tested three devices, at each of their four tension settings, in two separate sessions. Subjects could not see the true tension during the test. There were significant differences between the results for different subjects (p < 0.01) and instruments (p < 0.01) but not for different tension settings or between the two sessions. Overall mean measured tensions were 4.9 per cent (standard deviation, 4.4 per cent) below intended values. Tensions obtained at the maximum edge (completely occluded) on the scale markings were significantly (p < 0.001) closer to the nominal values (mean discrepancy, 3.6 per cent) than those at the minimum edge (mean discrepancy, 17.6 per cent). Several factors influence wire tension. Tensioning devices are not identical and the results obtained with them depend on the user. If the scale markings are completely occluded, the discrepancy between intended and actual tensions of around 5 per cent is likely to be adequate for clinical practice since surgeons do not select the most suitable tension following quantitative data assessment, but rather it is a judgement based on surgical experience and consideration for the patient weight and expected level of activity.

Bone Wires↗
PubMed2004

A comparison of the torsional performance of stainless steel and titanium alloy tibial intramedullary nails: a clinically relevant approach.

In recent years there has been a tendency to design and manufacture intramedullary nails from titanium alloy rather than from stainless steel. The aim of this project was to compare the torsional performance of one manufacturers standard stainless steel and titanium alloy tibial intramedullary nails, using their distal locking screw holes and dedicated cross screws to secure each nail distally. A custom built test rig and materials testing machine were used to determine the torsional rigidity of the nails. Theory was used to calculate the torsional rigidity of the central parts of each nail. From the mechanical testing, the mean torsional rigidity of the titanium alloy nail system was 40.9 N m2 while that of the stainless steel nail system was 34.6 N m2, for all distal interlocking screw positions tested. Based on theoretical calculations the torsional rigidity of the central part of the nail was 83 N m2 for the stainless steel nail and 66 N m2 for the titanium alloy nail. This study shows the importance of using the distal locking screw holes and dedicated cross screws to secure intramedullary nails during mechanical testing so that clinically relevant results are obtained about the whole nail system and not just the nail.

Alloys↗
PubMed2003

Synchronously pumped CdSe optical parametric oscillator in the 9-10 microm region.

Continuous mode-locked operation of a singly resonant, synchronously pumped optical parametric oscillator (SPOPO) based on CdSe has produced idler output tuned over the range of 9.1-9.7 microm, the longest wavelength generated so far to our knowledge from a SPOPO. Average idler powers as high as approximately 70 mW are generated in the crystal. Tandem pumping with a diffraction-grating-tuned parametric oscillator in periodically poled lithium niobate provides a convenient and agile means of tuning the noncritically phase-matched CdSe device. The absence of any detrimental thermal effects in the CdSe crystal suggests that significant further power scaling should be possible, with idler tuning ranges extendable to cover 8-12 microm.

Journal Article↗
PubMed2003

The effect of clamping a tensioned wire: implications for the Ilizarov external fixation system.

This study demonstrates that clamping a tensioned wire can cause a reduction in wire tension. Tension (about 1275 N) was applied to a wire that was subsequently clamped, using cannulated bolts, to the steel half-ring of an Ilizarov external fixator. The tension in the wire was monitored before, during and after clamping. The apparatus was disassembled and the deformations in the wire caused by the clamps were measured. This experiment was repeated 15 times. When the wire was clamped to the frame, the wire tension was reduced by 22 +/- 7 per cent (mean +/- standard deviation, SD). The drop in wire tension was linearly correlated (r = 0.96; p < 0.001) with the deformation caused by the bolts. A finite element (FE) model of the wire was also constructed. The model was pre-stressed (tensioned), and the clamping effect replicated. This analysis showed that clamping the wire could be considered to squeeze the wire outwards (like toothpaste from a tube) and so reduce its tension during fixator assembly. To assess the magnitude of this effect in the clinical situation, the FE model analysis was repeated to replicate clamping a 1.8-mm-diameter wire to a 180-mm-diameter steel Ilizarov ring component. The analysis showed that for these conditions the tension reduced by 8-29 per cent. The results of this study highlight a general engineering problem: how can a tensioned wire be secured to a structure without an appreciable loss of tension? If the performance of the structure depends on the wire tension, this performance will change when the wire is secured.

Bone Wires↗
PubMed2003

Yielding of the clamped-wire system in the Ilizarov external fixator.

This study demonstrates that the clamped-wire system used to suspend bones within an Ilizarov external fixator yields when the perpendicular load exceeds 50 N per wire. Cyclic loading was applied to tensioned wires clamped within an Ilizarov ring component, with steadily increasing load amplitude. Wires were tested at four initial tension settings. The amount of energy lost within the clamped-wire system per load cycle was calculated for every test. The results showed that there was a consistent trend to increasing non-recoverable energy loss per load cycle when peak loads exceed 50 N for all initial tension settings. A finite element (FE) model replicating the experimental conditions was performed to investigate the levels of stress within the loaded wires. The FE model analyses showed that high stresses were generated in the wires close to the clamping sites, and that the stress levels could reasonably be expected to exceed the material yield stress when loaded to about 55 N, for all initial tension settings. The results show that material yield, accompanied by some wire slippage through the clamps, is responsible for system yield, in agreement with previous studies. Although the initial wire tension has an appreciable effect on the wire stiffness, it did not affect the elastic load range of the clamped-wire system. To prevent yield of the clamped-wire system in practice, the fixator should be assembled with sufficient wires to ensure that the load transmitted to each wire by the patient does not exceed 50 N.

Bone Wires↗
PubMed2002

Peanut hull pellets as a single use sorbent for the capture of Cu(II) from wastewater.

This paper investigates the ability of peanut hulls and peanut hull pellets to adsorb copper from dilute aqueous metal ion solutions in batch and fixed bed systems. The kinetics of copper uptake onto the media have been investigated in batch systems and the influence of pH and particle size on the rate and extent of copper capture determined. The Langmuir and Freundlich isotherm theories were determined; the Langmuir model was found to best represent the equilibrium isotherm data. In normalized kinetic tests at least 75% of copper removal occurred within the first 20 min; 92% removal was effected within the first 50 min. The rate of uptake was optimum within the pH range 5-7.5, and media capacities remained relatively constant at a pH above 4.0. Bench-scale column studies were performed using peanut hull pellets. The overall capacity of pelletized peanut hulls was higher than for unmodified peanut hulls. Due to their demonstrated ability for Cu(II) uptake and favorable structural characteristics, pelletized peanut hulls could gain use as a low-cost, once-through biomass filter medium for copper-bearing waste streams.

Adsorption↗
PubMed2002

Finite element analysis of stress around a sternum screw used to prevent sternal dehiscence after heart surgery.

The sternum screw has been proposed as a means of preventing sternal dehiscence, following heart surgery, by increasing the contact area between the wire used to close the median sternotomy and the surrounding bone; as a result, the contact stress is reduced. A finite element model was constructed of a cylindrical wire or screw passing through a block of sternum which consisted of cancellous bone sandwiched within a cortical shell. The thickness of the cortical shell and the material properties of bone were varied between reasonable values. The stress distribution in the sternum was calculated for each model when the wire was subjected to a tension (250 N) which would be required for six wires to withstand a strong cough (40 kPa). Results were validated by comparison with a simple analytical model in which the bone and wire were considered incompressible. They show that the screw reduces the contact stress to almost one-seventh of its value when wire is used alone. Contact stresses are especially high if the cortical shell is thin. The high stress in the bone around a screw falls off within a few millimetres. As a result, no problems are anticipated in placing six screws in each half-sternum so that the sternotomy may be closed with the usual six wires.

Bone Screws↗
PubMed2001

Liver X receptor (LXR) regulation of the LXRalpha gene in human macrophages.

The nuclear oxysterol receptors LXRalpha (NR1H3) and LXRbeta (NR1H2) coordinately regulate the expression of genes involved in the transport and catabolism of cholesterol. In macrophages, LXR stimulates the transcription of genes encoding transporters involved in cholesterol efflux, which may limit the transformation of these cells into foam cells in response to lipid loading. Here, we report that natural and synthetic LXR ligands induce the expression of the LXRalpha gene in primary human macrophages and differentiated THP-1 macrophages. This regulation was not observed in primary human adipocytes or hepatocytes, a human intestinal cell line, or in any mouse tissue or cell line examined. The human LXRalpha gene was isolated, and the transcription initiation site delineated. Analysis of the LXRalpha promoter revealed a functional LXR/RXR binding site approximately 2.9 kb upstream of the transcription initiation site. We conclude that LXRalpha regulates its own expression in human macrophages and that this response is likely to amplify the effects of oxysterols on reverse cholesterol transport. These findings underscore the importance of LXR as a potential therapeutic target for the treatment of atherosclerosis.

Animals↗
PubMed2001

Expression profiling reveals hepsin overexpression in prostate cancer.

Prostate cancer is the most commonly diagnosed noncutaneous cancer in men. Despite this fact, many of the genetic changes that coincide with prostate cancer progression remain enigmatic. We have addressed this problem by characterizing the expression profiles of several benign and malignant human prostate samples, and we have identified several genes that are differentially expressed between benign and malignant glands. One gene that was overexpressed encodes the serine protease hepsin. We used an independent sample set to confirm that hepsin is overexpressed in prostate tumors, and in situ hybridization demonstrates that hepsin is specifically overexpressed in the carcinoma cells themselves. These facts, together with the molecular properties of hepsin, make it an ideal target for prostate cancer therapy.

Gene Expression Profiling↗
PubMed2001

Pharmacophore analysis of the nuclear oxysterol receptor LXRalpha.

A cell-free assay was developed for the orphan nuclear receptor LXRalpha that measures the ligand-dependent recruitment of a peptide from the steroid receptor coactivator 1 (SRC1) to the nuclear receptor. Using this ligand-sensing assay (LiSA), the structural requirements for activation of the receptor by oxysterols and related compounds were studied. The minimal pharmacophore for receptor activation was shown to be a sterol with a hydrogen bond acceptor at C24. 24(S),25-Epoxycholesterol (1), which meets this criterion, is among the most efficacious of the oxysterols and is an attractive candidate as the LXRalpha natural hormone. Cholenic acid dimethylamide (14) showed increased efficacy compared to 1, whereas the unnatural oxysterol 22(S)-hydroxycholesterol (4) was shown to be an antagonist of 1 in the LiSA. The structural requirements for SRC1 recruitment in the LiSA correlated with the transcriptional activity of compounds in a cell-based reporter assay employing LXRalpha-GAL4 chimeric receptors. Site-directed mutagenesis identified Trp(443) as an amino acid critical for activation of LXRalpha by oxysterol ligands. This information was combined with the structure-activity relationship developed from the LiSA to develop a 3D homology model of LXRalpha. This model may aid the design of synthetic drugs targeted at this transcriptional regulator of cholesterol homeostasis.

Amino Acid Sequence↗
PubMed2001

Gene expression profiling with oligonucleotide microarrays distinguishes World Health Organization grade of oligodendrogliomas.

Oligodendrogliomas are the second most common type of glial neoplasm with distinct prognostic and therapeutic implications. Although refinements have led to improved clinical stratification, current grading schemes are still limited by subjective histopathological criteria. In this report, we have used oligonucleotide array technology to perform expression profiling in morphologically classic oligodendrogliomas. Expression information from approximately 1100 genes divided tumors into two molecularly distinct groups that corresponded exactly to their previously assigned histological grades. Subsequent gene clustering identified a subset of 196 transcripts showing a common, differential expression pattern between tumor grades. A number of these genes have been associated with the maintenance of cytoarchitecture, cellular differentiation and maturation, immunogenicity, and chemotherapeutic resistance. These results demonstrate the utility of gene expression profiling as an objective, ancillary tool for grading oligodendrogliomas and a potential approach for classifying diffuse gliomas where histological assessment may be difficult or ambiguous.

Adult↗
PubMed2001

Expression profiling of ductal carcinoma in situ by laser capture microdissection and high-density oligonucleotide arrays.

Gene expression profiling through the use of nucleic acid arrays is a powerful method for the molecular classification of human neoplasms. Laser capture microdissection is an equally useful technique to selectively isolate defined cell populations from heterogeneous histological tissue sections. In this report, we demonstrate how a modest use of laser capture microdissection is sufficient to isolate nanogram quantities of high-quality RNA. Together with the use of several internal standards and microcapillary electrophoresis of input RNA, two rounds of linear molecular amplification have been used to generate sufficient quantities of labeled target for hybridization to high-density oligonucleotide expression arrays. Results demonstrate that the technique is reproducible, generates only modest biasing of the original transcript population, and is comparable to the sensitivity achieved with standard methodology. Using this approach, we have compared the expression profiles of nonmalignant human breast epithelium and adjacent ductal carcinoma in situ lesions from breast cancer patients. Several genes, previously implicated in human breast cancer progression, demonstrate differential expression among the microdissected cell populations.

Breast↗
PubMed2001

Immunochemiluminescent focus assays for the quantitation of hepatitis A virus and rotavirus in cell cultures.

Two new immunological methods, the luminescent immunofocus assay (LIFA) and the luminescent immunofocus inhibition assay (LIF-IA), are described for the quantitation of cytopathic and non-cytopathic viruses propagated on cell culture monolayers. These methods use enhanced chemiluminescent detection to identify foci (luminescent immunofoci, LIF) of virus-infected cells. Viruses are propagated in susceptible cells under an agarose overlay, inactivated with ultraviolet irradiation, lifted onto nitrocellulose membranes, and probed with virus-specific monoclonal or polyclonal antibody followed by a second antibody conjugated to horseradish peroxidase. Membranes are then treated with a luminol-based detection reagent and exposed to light sensitive film for up to 10 min. The film is developed and foci appear as dark, discrete spots which are proportional to the dose of each virus. The LIFA detected both cytopathic and non-cytopathic hepatitis A viruses (HAV) and simian rotavirus. For the cytopathic HAV, the LIFA and plaque counts were comparable. The LIF-IA was developed for HAV using virus-specific antiserum which effectively attenuated LIF formation. The LIFA and LIF-IA may be completed 5 days faster than conventional radioimmunofocus assays for HAV and rotavirus and do not require the use of radiolabeled antibodies, offering safety advantages and making these techniques more adaptable for general use. Luminescent immunofocus assays should be useful for the detection and quantitation of virtually any cytopathic or non-cytopathic virus that can be propagated in monolayer cultures when virus-specific antiserum is available.

Animals↗
PubMed2001

Quantitative amplification of genomic DNA from histological tissue sections after staining with nuclear dyes and laser capture microdissection.

Laser capture microdissection (LCM) allows the selective sampling of tissue from histological sections. A prerequisite for this technique is the availability of histological dyes that do not interfere with downstream analysis of the sampled genetic material. We have examined the effect of four histological nuclear dyes (methyl green, hematoxylin, toluidine blue O, azure B) on TaqMan polymerase chain reaction amplification of beta-actin genomic DNA prepared from fixed and frozen tissue. Tissue sampled from the histological sections by manual dissection was compared with tissue sampled by LCM. As previously reported, when manually dissected tissue sections were analyzed, polymerase chain reaction amplification of DNA after hematoxylin staining was inferior to that after staining with the other dyes. In contrast, when tissue sampled by LCM was examined, DNA recovery after hematoxylin staining was equivalent to the recovery after methyl green staining. We conclude that DNA recovery from LCM-sampled tissue is independent of the histological stain chosen to highlight nuclear detail.

Cell Nucleus↗