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Biomedical subjects

M Jones

Publications and source records attributed to M Jones.

At least 55 records · Page 3Linked to original sources

Application of the FICTION technique for the simultaneous detection of immunophenotype and chromosomal abnormalities in routinely fixed, paraffin wax embedded bone marrow trephines.

The use of interphase fluorescence in situ hybridisation (FISH) to study cytogenetic abnormalities in routinely fixed paraffin wax embedded tissue has become commonplace over the past decade. However, very few studies have applied FISH to routinely fixed bone marrow trephines (BMTs). This may be because of the acid based decalcification methods that are commonly used during the processing of BMTs, which may adversely affect the suitability of the sample for FISH analysis. For the first time, this report describes the simultaneous application of FISH and immunofluorescent staining (the FICTION technique) to formalin fixed, EDTA decalcified and paraffin wax embedded BMTs. This technique allows the direct correlation of genetic abnormalities to immunophenotype, and therefore will be particularly useful for the identification of genetic abnormalities in specific tumour cells present in BMTs. The application of this to routine clinical practice will assist diagnosis and the detection of minimal residual disease.

Antigens, CD20↗

Do u smoke after txt? Results of a randomised trial of smoking cessation using mobile phone text messaging.

OBJECTIVES: To determine the effectiveness of a mobile phone text messaging smoking cessation programme. DESIGN: Randomised controlled trial SETTING: New Zealand PARTICIPANTS: 1705 smokers from throughout New Zealand who wanted to quit, were aged over 15 years, and owned a mobile phone were randomised to an intervention group that received regular, personalised text messages providing smoking cessation advice, support, and distraction, or to a control group. All participants received a free month of text messaging; starting for the intervention group on their quit day to assist with quitting, and starting for the control group at six months to encourage follow up. Follow up data were available for 1624 (95%) at six weeks and 1265 (74%) at six months. MAIN OUTCOME MEASURES: The main trial outcome was current non-smoking (that is, not smoking in the past week) six weeks after randomisation. Secondary outcomes included current non-smoking at 12 and 26 weeks. RESULTS: More participants had quit at six weeks in the intervention compared to the control group: 239 (28%) v 109 (13%), relative risk 2.20 (95% confidence interval 1.79 to 2.70), p < 0.0001. This treatment effect was consistent across subgroups defined by age, sex, income level, or geographic location (p homogeneity > 0.2). The relative risk estimates were similar in sensitivity analyses adjusting for missing data and salivary cotinine verification tests. Reported quit rates remained high at six months, but there was some uncertainty about between group differences because of incomplete follow up. CONCLUSIONS: This programme offers potential for a new way to help young smokers to quit, being affordable, personalised, age appropriate, and not location dependent. Future research should test these findings in different settings, and provide further assessment of long term quit rates.

Adolescent↗

Integration of neural responses originating from different regions of the cortical somatosensory map.

The neural pathways responsible for detecting peripheral tactile stimuli are well known; however, the interactions between different somatosensory regions have been less well investigated. This study demonstrates how the contralateral sensory response of rat barrel cortex to whisker stimulation is affected by stimulation of contralateral forepaw and ipsilateral whisker and forepaw. The barrel cortex in the right hemisphere was located using optical imaging. A 16-channel multielectrode was used to measure field potentials evoked by contralateral electrical stimulation of the whisker pad. A standard response in the right barrel cortex to single pulse electrical stimulation of the contralateral whisker pad was modulated by applying conditioning stimulation to one of three other regions of the body (the ipsilateral whisker pad, the ipsilateral or contralateral forepaws). In conditions where the standard contralateral whisker stimulus preceded the conditioning pulse, the size of response was identical to when it was stimulated alone. However, when the ipsilateral whisker and contralateral forepaw conditioning stimuli preceded the contralateral whisker pad stimulation, up to a 35% reduction in the contralateral whisker response was observed. These results confirm and extend previous studies [Proc. Natl. Acad. Sci. U. S. A. 97 (2000) 11026-11031; J. Neurosci. 21 (2001) 5251-5261], which show bilateral integration of neural activity within the rat somatosensory system. Furthermore, the longer latency of the inhibition following stimulation of the contralateral forepaw suggests the possible involvement of extracortical circuitry.

Animals↗

Measurement of the generalized forward spin polarizabilities of the neutron.

The generalized forward spin polarizabilities gamma(0) and delta(LT) of the neutron have been extracted for the first time in a Q2 range from 0.1 to 0.9 GeV2. Since gamma(0) is sensitive to nucleon resonances and delta(LT) is insensitive to the Delta resonance, it is expected that the pair of forward spin polarizabilities should provide benchmark tests of the current understanding of the chiral dynamics of QCD. The new results on delta(LT) show significant disagreement with chiral perturbation theory calculations, while the data for gamma(0) at low Q2 are in good agreement with a next-to-leading-order relativistic baryon chiral perturbation theory calculation. The data show good agreement with the phenomenological MAID model.

Journal Article↗

Measurement of the electric form factor of the neutron at Q2=0.5 and 1.0 GeV2/c2.

The electric form factor of the neutron was determined from measurements of the d-->(e-->,e'n)p reaction for quasielastic kinematics. Polarized electrons were scattered off a polarized deuterated ammonia (15ND3) target in which the deuteron polarization was perpendicular to the momentum transfer. The scattered electrons were detected in a magnetic spectrometer in coincidence with neutrons in a large solid angle detector. We find G(n)(E)=0.0526+/-0.0033(stat)+/-0.0026(sys) and 0.0454+/-0.0054+/-0.0037 at Q(2)=0.5 and 1.0 (GeV/c)(2), respectively.

Journal Article↗

Q2 evolution of the neutron spin structure moments using a 3He target.

We have measured the spin structure functions g(1) and g(2) of 3He in a double-spin experiment by inclusively scattering polarized electrons at energies ranging from 0.862 to 5.058 GeV off a polarized 3He target at a 15.5 degrees scattering angle. Excitation energies covered the resonance and the onset of the deep inelastic regions. We have determined for the first time the Q2 evolution of Gamma(1)(Q2)= integral (1)(0)g(1)(x,Q2)dx, Gamma(2)(Q2)= integral (1)(0)g(2)(x,Q2)dx, and d(2)(Q2)= integral (1)(0)x(2)[2g(1)(x,Q2)+3g(2)(x,Q2)]dx for the neutron in the range 0.1< or =Q2< or =0.9 GeV2 with good precision. Gamma(1)(Q2) displays a smooth variation from high to low Q2. The Burkhardt-Cottingham sum rule holds within uncertainties and d(2) is nonzero over the measured range.

Journal Article↗

Anaesthesia for endovascular treatment of cerebral aneurysms.

Endovascular treatment of cerebral aneuryms is now widely used and has important implications for the neuroanaesthetist. Significant issues include the decision to use general anaesthesia, factors associated with anaesthesia in the interventional radiology suite and treatment of complications. As endovascular treatment is now supported by evidence and established in practice, neuroanaesthetists should be involved in planning these procedures from a process, and individual patient, perspective.

Anesthesia↗

An improved method of microencapsulation and its evaluation to protect Lactobacillus spp. in simulated gastric conditions.

An improved method of microencapsulation was developed to increase the efficacy of capsules in protecting the encapsulated bacteria under simulated gastric conditions. Lactobacillus acidophilus CSCC 2400 was encapsulated in calcium alginate and tested for its survival in simulated gastric conditions. The effects of different capsule sizes (200, 450, 1000 microm), different sodium alginate concentrations (0.75%, 1%, 1.5%, 1.8% and 2% w/v) and different concentrations of calcium chloride (0.1, 0.2, 1.0 M) on the viability of encapsulated bacteria were investigated. The viability of the cells in the microcapsules increased with an increase in alginate capsule size and gel concentration. There was no significant difference (p>0.05) in the viability of encapsulated cells when the concentration of calcium chloride was increased. Increase in cell load during encapsulation increased the number of bacterial survivors at the end of 3-h incubation in simulated gastric conditions. Hardening the capsule in calcium chloride solution for a longer time (8 h) had no impact on increasing the viability of encapsulated bacteria in a simulated gastric environment. The release of encapsulated cells at different phosphate buffer concentrations was also studied. When encapsulated L. acidophilus CSCC 2400 and L. acidophilus CSCC 2409 were subjected to low pH (pH 2) and high bile concentration (1.0% bile) under optimal encapsulation conditions (1.8% (w/v) alginate, 10(9) CFU/ml, 30 min hardening in 0.1 M CaCl(2) and capsule size 450 microm), there was a significant increase (p<0.05) in viable cell counts, compared to the free cells under similar conditions. Thus the encapsulation method described in this study may be effectively used to protect the lactobacillus from adverse gastric conditions.

Alginates↗

Haemodynamic responses to sensory stimulation are enhanced following acute cocaine administration.

Cocaine enhances neural activity in response to sensory stimulation, an effect that may play a role in the development of drug craving. However, cocaine-induced sensory enhancement may be difficult to study in humans using neuroimaging if the global increases in baseline haemodynamic parameters, which cocaine produces, interfere with the ability of enhanced sensory-related neural activity to lead to enhanced haemodynamic responses. To investigate the effect of cocaine-induced baseline haemodynamic changes on sensory-related haemodynamic (and electrophysiological) responses, field potential (FP) and haemodynamic responses (obtained using optical imaging spectroscopy and laser-Doppler flowmetry) in the barrel cortex of the anaesthetised rat were measured during mechanical whisker stimulation following cocaine (0.5 mg/kg) or saline administration. During cocaine infusion, the relationship between blood flow and volume transiently decoupled. Following this, cocaine caused large baseline increases in blood flow (133%) and volume (33%), which peaked after approximately 6 min and approached normal levels again after 25 min. During the peak baseline increases, FP responses to whisker stimulation were similar to saline whereas several haemodynamic response parameters were slightly reduced. After the peak, significant increases in FP responses were observed, accompanied by significantly enhanced haemodynamic responses, even though the haemodynamic baselines remained elevated. Hence, the haemodynamic response to sensory stimulation is transiently reduced in the presence of large increases in baseline but, after the baseline peak, enhanced neural responses are faithfully accompanied by enhanced haemodynamic responses. The findings suggest that any cocaine-induced enhancement of sensory-related neural activity in humans is likely to be detectable by neuroimaging.

Animals↗

Determination of the T cell epitopes of the lipocalin allergen, Rat n 1.

BACKGROUND: Laboratory animal allergy (LAA) is an important cause of occupational sensitization and asthma. Rats are a frequent cause of LAA and the major rat allergen, Rat n 1, is a member of the lipocalin protein family, which includes several other animal allergens such as the cow allergen, Bos d 2. To date, Bos d 2 is the only mammalian lipocalin allergen to have been studied in detail. OBJECTIVE: We undertook a cross-sectional study of a large population of individuals exposed to laboratory rats to determine the proliferative responses of peripheral blood mononuclear cells (PBMCs) to the major rat allergen, Rat n 1. METHODS: Eighty-three cases (defined by a positive skin prick test (SPT) > or =3 mm and/or a positive RAST > or =2% binding) and 274 referents without specific IgE to rats were tested for their proliferative responses of PBMCs to rat allergen. Cytokine release to rat urinary protein was examined in 28 sensitized and 42 non-sensitized exposed individuals. RESULTS: Proliferation to rat urinary protein was weak in all individuals. Four regions within Rat n 1 were identified as containing potential immunodominant T cell epitopes and three of these co-localized within the conserved regions of the lipocalin molecule. All four regions within Rat n 1 overlapped considerably with the characterized epitopes of the lipocalin allergen, Bos d 2. IL-5 and ratios of IL-5/IFN-gamma were significantly increased in cases. CONCLUSION: The response to Rat n 1 is remarkably similar to the cow lipocalin allergen Bos d 2. T cell epitopes within lipocalins appear to co-localize with the conserved regions of the molecule. LAA is characterized by an increased production of IL-5. Investigation of other lipocalin allergens will provide further information about the allergenicity of this group of proteins.

Allergens↗

Efficacy and tolerability of sumatriptan tablets administered during the mild-pain phase of menstrually associated migraine.

Two randomised, double-blind, parallel-group, placebo-controlled clinical trials were conducted to assess the efficacy of sumatriptan tablets, 50mg and 100mg, for treatment during the mild-pain phase of a menstrually associated migraine among patients who typically experienced moderate to severe migraine preceded by an identifiable phase of mild pain. Subjects (n = 403 in Study 1 and n = 349 in Study 2) treated one menstrually associated migraine on an outpatient basis. The results demonstrate that sumatriptan tablets, 50 mg or 100 mg, were significantly more effective than placebo at conferring pain-free response 1 h and 2 h post-dose; migraine-free response (i.e. no pain and no associated symptoms) 2 h post-dose; returning patients to normal functioning 2 h post-dose; and conferring sustained freedom from pain from 2 through 24 h post-dose. Although the studies were not designed or statistically powered to show differences between the sumatriptan doses, a trend for slightly higher efficacy was observed for the 100-mg dose compared with the 50-mg dose on many measures. Both doses of sumatriptan were well-tolerated. The only adverse events reported in more than 2% of subjects in a treatment group were nausea, paresthesia, dizziness and malaise/fatigue, all of which were reported at incidences comparable to or slightly higher than those with placebo. Considered in the context of other findings, these data suggest that--with menstrually associated migraine as with non-menstrual migraine--optimal therapeutic benefit of sumatriptan tablets may be realised when they are administered during the mild-pain phase of an attack rather than delaying treatment until headache is moderate or severe.

Adolescent↗

Characteristics of murine histidinaemia and its potential for genetic manipulation.

BACKGROUND: Histidinaemia is an autosomal recessive disorder affecting the hepatic enzyme histidine ammonia lyase (histidase) resulting in elevated plasma and urinary histidine and is prototypic of a series of hepatic cytosolic enzyme defects. AIMS: To characterise the physiology of murine histidinaemia with respect to histidine excretion and catabolism, and explore the potential for manipulating cellular and whole body histidase metabolism by gene transfer. MATERIALS AND METHODS: We studied his/his mice which have a G to A substitution in the gene encoding histidase, using both in vitro transduction of isolated hepatocytes by lipofection with wild-type histidase cDNA, and in vivo transduction of whole liver using a retroviral construct. RESULTS AND CONCLUSION: Histidase cDNA expression restored histidase activity in vivo and in vitro towards normal levels, demonstrated both at the cellular level and by whole body metabolic studies, establishing the potential of this model for the development of new gene therapeutic approaches.

Amino Acid Metabolism, Inborn Errors↗

Mapping of the immunodominant T cell epitopes of the protein topoisomerase I.

OBJECTIVES: To identify the immunodominant T cell epitopes of the topoisomerase I protein in patients with systemic sclerosis (SSc) and control subjects, using computational analysis software (TEPITOPE) and T cell proliferation assays. METHODS: Six oligopeptides, predicted by TEPITOPE software as potential topoisomerase protein epitopes, were used to perform T cell proliferation assays in 21 patients with SSc and 15 healthy controls. RESULTS: A positive response to at least one of the peptides was seen in 10/21 patients and 7/15 healthy controls. Among responders, the proliferative response was limited to a single peptide in 6/7 healthy controls, whereas 5/10 patients responded to more than one peptide. In responding patients a significant correlation was found between disease duration and number of peptides inducing a response (p = 0.007). CONCLUSIONS: Several T cell epitopes of the topoisomerase I protein have been identified and evidence has been found to suggest epitope spreading in patients with SSc.

Adult↗

Left ventricular systolic function and diastolic filling after intermittent high intensity team sports.

BACKGROUND: Prolonged steady state exercise can lead to a decrease in left ventricular (LV) function as well as promote the release of cardiac troponin T (cTnT). There is limited information on the effect of intermittent high intensity exercise of moderate duration. OBJECTIVES: To determine the effect of intermittent high intensity exercise of moderate duration on LV function. METHODS: Nineteen male rugby and football players (mean (SD) age 21 (2) years) volunteered. Assessments, before, immediately after, and 24 hours after competitive games, included body mass, heart rate (HR), and systolic blood pressure (sBP) as well as echocardiography to assess stroke volume (SV), ejection fraction (EF), systolic blood pressure/end systolic volume ratio (sBP/ESV), and global diastolic filling (E:A) as well as to indirectly quantify preload (LV internal dimension at end diastole (LVIDd)). Serum cTnT was analysed using a 3rd generation assay. Changes in LV function were analysed by repeated measures analysis of variance. cTnT data are presented descriptively. RESULTS: SV (91 (26) v 91 (36) v 90 (35) ml before, after, and 24 hours after the game respectively), EF (71 (8) v 70 (9) v 71 (7)%), and sBP/ESV (4.2 (1.8) v 3.8 (1.9) v 4.1 (1.6) mm Hg/ml) were not significantly altered (p>0.05). Interestingly, whereas LVIDd was maintained after the game (50 (5) v 50 (6) mm), sBP was transiently but significantly reduced (131 (3) v 122 (3) mm Hg; p<0.05). E:A was moderately (p<0.05) reduced after the game (2.0 (0.4) v 1.5 (0.4)) but returned to baseline within 24 hours. No blood sample contained detectable levels of cTnT. CONCLUSIONS: In this cohort, LV systolic function was not significantly altered after intermittent activity. A transient depression in global diastolic filling was partially attributable to a raised HR and could not be explained by myocyte disruption as represented by cTnT release.

Adult↗

Screening for physical and psychological illness in the British Armed Forces: I: The acceptability of the programme.

OBJECTIVES: To assess the response to a self-administered questionnaire and attendance of a medical centre for physical and psychological health screening. METHODS: 4500 men and women from the three services were randomly selected to receive either a full or abridged screening questionnaire. The full questionnaire included the General Health Questionnaire-12 (GHQ-12) and Post-traumatic Stress Disorder (PTSD) checklist, 15 symptoms, a self-assessed health status question and three questions on alcohol behaviour (WHO Audit). The abridged questionnaire included GHQ-4, a slightly shortened PTSD checklist and five symptoms, but excluded questions on alcohol behaviour. All 'screen-positive' and a random 'screen-negative' sample were invited to attend a medical centre. RESULTS: 67.1% of the servicemen completed a questionnaire; slightly but significantly more the abridged than the full questionnaire (4.9%, 95% confidence interval 2.3-7.4%). Of those receiving a full or abridged questionnaire, 32% and 22.5% respectively were 'screen-positives', most of the difference (7.5%) attributable to alcohol behaviour. Less than 30% of the servicemen invited to attend a medical centre accepted the invitation, even fewer during the preparation for deployment to Iraq. Those who fulfilled the criteria for PTSD, alcohol behaviour or multi-criteria 'screen-positive' were more reluctant than controls to attend. CONCLUSIONS: Screening for psychological illness has little support among servicemen, perhaps because they may not wish to share concerns with a military doctor. Avoidance behaviour among those with a psychological condition may also selectively reduce willingness to attend a medical centre. Screening during pre-deployment periods has even less support than at other times.

Adult↗