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J McEwen

Publications and source records attributed to J McEwen.

At least 19 recordsLinked to original sources
PubMed2001

Conserved function of Caenorhabditis elegans UNC-30 and mouse Pitx2 in controlling GABAergic neuron differentiation.

We are taking a cross-species approach to identify genes that are required for mammalian GABAergic neuron differentiation. On the basis of homeodomain similarity, the vertebrate Pitx genes appear to be orthologs of unc-30, a Caenorhabditis elegans gene necessary for differentiation of the GABAergic phenotype of type D neurons. One of the Pitx genes, Pitx2, is expressed in regions of GABAergic neurogenesis in the mammalian brain. These observations led us to test the functional conservation of the mouse Pitx2 and worm unc-30 genes using a rescue assay. Pitx2 rescues the GABAergic differentiation defect and partially rescues the axon guidance and behavioral phenotypes of unc-30 mutants, indicating a high degree of functional conservation between these evolutionarily related genes. Previous studies show that UNC-30 directly regulates the unc-25/glutamate decarboxylase gene that encodes the enzyme for GABA synthesis. We find that the promoter regions of the mouse and human genes coding for the 67 kDa glutamate decarboxylase (Gad1) also contain binding sites matching the UNC-30/Pitx2 consensus binding site sequence. We show that these sites specifically bind to Pitx2 protein in vitro and that in transfected neuroblastoma cells, the Pitx2 binding sites contribute to the basal activity of the Gad1 promoter. Furthermore, in cotransfection experiments, we find that Pitx2 strongly activates the Gad1 promoter. These results indicate that Pitx2 may regulate Gad1 expression in mammals, suggesting a new role for this key developmental transcription factor as a regulator of GABAergic differentiation during mammalian neural development. Our results suggest that some of the mechanisms regulating GABAergic differentiation are evolutionarily conserved.

Animals↗
PubMed2001

Resolution of pluripotential intermediates in murine hematopoietic differentiation by global complementary DNA amplification from single cells: confirmation of assignments by expression profiling of cytokine receptor transcripts.

Although hematopoiesis is known to proceed from stem cells through a graded series of multipotent, oligopotent, and unipotent precursor cells, it has been difficult to resolve these cells physically one from another. There is, therefore, corresponding uncertainty about the exact distribution and timing of the expression of genes known to be important in hematopoietic differentiation. In earlier work, the generation of a set of amplified complementary DNAs (cDNAs) from single precursor cells was described, whose biologic potential was determined by the outcome of cultured sibling cells. In this study, the new acquisition of cDNA from multipotent myeloid precursor cells is described, as is the mapping of RNA-level expression of 17 distinct cytokine receptors (c-kit, Flk-1, Flk-2/Flt-3, c-fms, gp130, erythropoietin receptor, GM-CSFRalpha, G-CSFR, TNFR1, IL-1RI, IL-1RII, IL-2Rbeta, IL-3-specific beta receptor, IL-4R, IL-6Ralpha, IL-7Ralpha, and IL-11Ralpha) to the enlarged sample set, spanning stages from pentapotent precursors through oligopotent intermediates to committed and maturing cells in the myeloid and lymphoid lineages. Although the enhanced scope and resolving power of the analysis yielded previously unreported observations, there was overall agreement with known biologic responsiveness at individual stages, and major contradictions did not arise. Moreover, each precursor category displayed a unique overall pattern of hybridization to the matrix of 17 receptor probes, supporting the notion that each sample pool indeed reflected a unique precursor stage. Collectively, the results provide supportive evidence for the validity of the cDNA assignments to particular stages, the depth of the information captured, and the unique capacity of the sample matrix to resolve individual stages in the hematopoietic hierarchy.

Animals↗
PubMed2001

Changes in blood pressure among students attending Glasgow University between 1948 and 1968: analyses of cross sectional surveys.

OBJECTIVES: To examine the changes in blood pressure over time in a cohort of young adults attending university between 1948 and 1968. DESIGN: Cross sectional study. SETTING: Glasgow University. PARTICIPANTS: 12 414 students aged 16-25 years-9248 men (mean age 19.9 years) and 3164 women (19.2 years)-who participated in health screening on entering university between 1948 and 1968. MAIN OUTCOME MEASURES: Systolic and diastolic blood pressure. RESULTS: In male students mean systolic blood pressure adjusted for age decreased from 134.5 (95% confidence interval 133.8 to 135.2) mm Hg in those born before 1929 to 125.7 (125.0 to 126.3) mm Hg in those born after 1945, and diastolic blood pressure dropped from 80.3 (79.8 to 80.8) mm Hg to 74.7 (74.2 to 75.1) mm Hg. For female students the corresponding declines were from 129.0 (127.5 to 130.5) mm Hg to 120.6 (119.8 to 121.4) mm Hg and from 79.7 (78.7 to 80.6) mm Hg to 77.0 (76.5 to 77.5) mm Hg. Adjustment for potential confounding factors made little difference to these findings. The proportion of students with hypertension declined substantially in both sexes. CONCLUSIONS: Substantial declines in systolic and diastolic blood pressure over time were occurring up to 50 years ago in young adults who were not taking antihypertensive medication. Since blood pressure tracks into adult life, the results of the cross sectional comparisons suggest that factors acting in early life may be important in determining population risk of cardiovascular disease. Changes in such factors may have made important contributions to the decline in rates of cardiovascular diseases, particularly stroke, seen in developed countries during the past century.

Adolescent↗
PubMed2000

Disability in young people and adults one year after head injury: prospective cohort study.

OBJECTIVE: To determine the frequency of disability in young people and adults admitted to hospital with a head injury and to estimate the annual incidence in the community. DESIGN: Prospective, hospital based cohort study, with one year follow up of sample stratified by coma score. SETTING: Five acute hospitals in Glasgow. SUBJECTS: 2962 patients (aged 14 years or more) with head injury; 549 (71%) of the 769 patients selected for follow up participated. MAIN OUTCOME MEASURES: Glasgow outcome scale and problem orientated questionnaire. RESULTS: Survival with moderate or severe disability was common after mild head injury (47%, 95% confidence interval 42% to 52%) and similar to that after moderate (45%, 35% to 56%) or severe injury (48%, 36% to 60%). By extrapolation from the population identified (90% of whom had mild injuries), it was estimated that annually in Glasgow (population 909 498) 1400 young people and adults are still disabled one year after head injury. CONCLUSION: The incidence of disability in young people and adults admitted with a head injury is higher than expected. This reflects the high rate of sequelae previously unrecognised in the large number of patients admitted to hospital with an apparently mild head injury.

Adolescent↗
PubMed2000

CNS-induced deficits of heavy particle irradiation in space: the aging connection.

Our research over the last several years has suggested that young (3 mo) rats exposed to whole-body 56Fe irradiation show neuronal signal transduction alterations and accompanying motor behavioral changes that are similar to those seen in aged (22-24 mo) rats. Since it has been postulated that 1-2% of the composition of cosmic rays contain 56Fe particles of heavy particle irradiation, there may be significant CNS effects on astronauts on long-term space flights which could produce behavioral changes that could be expressed during the mission or at some time after the return. These, when combined with other effects such as weightlessness and exposure to proton irradiations may even supercede mutagenic effects. It is suggested that by determining mechanistic relationships that might exist between aging and irradiation it may be possible to determine the common factor(s) involved in both perturbations and develop procedures to offset their deleterious effects. For example, one method that has been effective is nutritional modification.

Aging↗
PubMed2000

Effects of exposure to heavy particles on a behavior mediated by the dopaminergic system.

The effects of exposure to heavy particles on behaviors mediated by the central nervous system (CNS) are qualitatively different than the effects produced by exposure to other types of radiation. One behavior mediated by the CNS is the amphetamine-induced taste aversion, which is produced by pairing a novel tasting solution with injection of amphetamine. When the conditioning day is three days following irradiation, exposing rats to low doses of 56Fe particles (600 MeV/n or 1 GeV/n) eliminates the taste aversion produced by injection of amphetamine, which is dependent upon the integrity of the central dopaminergic system, but has no effect on the aversion produced by injection of lithium chloride which is mediated by the gastrointestinal system. In contrast to the effects obtained using heavy particles, exposing rats to 60CO gamma rays or to fission spectrum neutrons has no selective effect upon the acquisition of either amphetamine- or lithium chloride-induced taste aversions. When the conditioning day occurs four months following exposure to 1 GeV/n 56Fe particles, there is an enhancement of the amphetamine-induced taste aversion. The implications of these findings for approaches to risk assessment are considered.

Amphetamine↗
PubMed2000

Determinants of adolescent blood pressure: findings from the Glasgow University student cohort.

OBJECTIVE: To establish whether the blood pressure (BP) of young adults is related to their physical or behavioural attributes. DESIGN: Cross-sectional study. SUBJECTS: A total of 11,284 males and 3491 females who attended the University of Glasgow between 1948 and 1968. OUTCOME MEASURES: Systolic and diastolic BP. RESULTS: Body mass index (BMI) and weight were positively associated with BP in males and females. Height had a small positive association with male systolic BP and female diastolic BP. Haemoglobin levels were associated with raised BP in females. Albuminuria was associated with raised BP in males but not females. Smoking and alcohol consumption were associated with small negative effects on BP, although the measurement of alcohol consumption in the study was crude, and these results may not be free of confounding. Insufficient outdoor exercise was associated with higher BP in females but not males. No social class gradients in BP levels were seen, although having a higher number of siblings was associated with slightly lower BP in males. CONCLUSION: The results from the current study indicate that modifiable risk factors, such as weight and exercise affect the BP of young adults. The impact of these factors, coupled with the known tracking of BP from adolescence to adulthood, emphasise the importance of healthy behaviour patterns in young people.

Adolescent↗
PubMed2000

Height and cancer mortality: results from the Glasgow University student cohort.

The aim of the study was to examine the association between height and cancer mortality in a socially homogeneous group of subjects. The study was based on a cohort of students, 8397 men and 2329 women, aged 16-30 y, who attended the University of Glasgow between 1948 and 1968. Mean follow-up time was 40 y. Height was measured at a medical examination performed at the student health service. The outcome measures used in the study were all-cause mortality and mortality from: all cancers, smoking and non-smoking related cancers and cancers related to sex hormones. No substantial or statistically significant associations were seen between height and all-cause or all-cancer mortality in either sex. Neither were any significant associations found between height and any of the sub-types of cancer studied (ie those related to smoking, those not related to smoking, and those related to sex hormones). Previous observations which have shown positive associations between height and cancer mortality have generally been based on populations with diverse social origins, among whom the variation in height will reflect variation in health and nutrition in childhood. The relatively low level of such variation in the present study may account for the negative findings. Public Health (2000) 114, 451-455

Adolescent↗
PubMed2000

A comparison of the photosensitizing potential of trovafloxacin with that of other quinolones in healthy subjects.

Treatment with some quinolones is associated with an abnormal skin reaction following exposure to sunlight (photosensitivity). The objective of the current study was to compare the photosensitizing potential of a new quinolone, trovafloxacin, with that of ciprofloxacin, lomefloxacin and placebo. Forty-eight healthy males (age range 19-45 years) were randomized to receive a 7 day course of treatment with: (i) trovafloxacin 200 mg od; (ii) ciprofloxacin 500 mg bd; (iii) lomefloxacin 400 mg od; or (iv) placebo bd. Minimal erythema doses (MEDs) were assessed using a monochromator at baseline and on day 5 of treatment, for wavelengths of 305 +/- 5, 335 +/- 30, 365 +/- 30, 400 +/- 30 and 430 +/- 30 nm; 335 +/- 30 and 365 +/- 30 nm are within the UVA range. Immediate reaction MEDs were similar in all treatment groups. However, between baseline and day 5, the mean decreases in delayed-reaction MED (24 h) at 335 +/- 30 nm were only 18.99% for trovafloxacin versus placebo (P = 0.1267), compared with 53.77% (P 0.0001) and 64.13% (P 0.0001) for ciprofloxacin and lomefloxacin, respectively. Similarly, at 365 +/- 30 nm, trovafloxacin produced the smallest reduction in delayed MED versus placebo (43.66%), compared with ciprofloxacin (61.53%) and lomefloxacin (75.81%). These differences between trovafloxacin and ciprofloxacin and lomefloxacin were significant at both 335 +/- 30 and 365 +/- 30 nm (P 0.029). All MED values returned to baseline levels within 2 days of drug cessation. These results show that trovafloxacin has significantly less photosensitizing potential than either ciprofloxacin or lomefloxacin. This photosensitivity appears to be induced only by wavelengths in the UVA region, is maximal at 24 h and is a short-term effect.

Adult↗
PubMed2000

The acute effects of amisulpride (50 mg and 200 mg) and haloperidol (2 mg) on cognitive function in healthy elderly volunteers.

In this double-blind, placebo controlled, four-way cross-over trial in 16 healthy elderly volunteers, the acute effects of haloperidol 2 mg, amisulpride 50 mg and 200 mg, were assessed on a range of tests of cognitive function. On each study day, cognitive performance was assessed prior to dosing and at 2, 4, 6, 9, 12 and 24 h after dosing with the following tests from the Cognitive Drug Research computerized assessment system: simple reaction time, digit vigilance task, choice reaction time, visual tracking, Critical Flicker Fusion, body sway, numeric working memory, immediate and delayed word recall, word recognition and self-ratings of mood and alertness. Haloperidol showed a general tendency to impair performance, and although this did not reach significance compared to placebo, for two tasks there were significant impairments with haloperidol compared to amisulpride. Amisulpride 50 mg and 200 mg, was not associated with impairment. In fact, there was some suggestion of improvement over placebo on three measures. The timings of assessment were appropriate for the study compounds. Furthermore, in a recent study in which a smaller number of elderly volunteers was tested on the same cognitive assessment system, a clear profile of acute impairments of haloperidol 3 mg, was identified. This indicates that haloperidol 2 mg, is not a sufficient dose to affect cognitive function in the elderly, supporting the general absence of effects with this dose in the young. Thus, the general absence of cognitive impairments with amisulpride at the doses used in this study suggests that this compound does not impair cognitive function in the elderly.

Aged↗
PubMed2000

Needs assessment in primary care: general practitioners' perceptions and implications for the future.

BACKGROUND: Health needs assessment can guide the appropriate shift to primary care by identifying the most effective and efficient resource allocation to meet the needs of populations. Assessing health care needs will be a continuing challenge for primary care trusts in Scotland (or equivalent groups in other parts of the United Kingdom); however, lessons must be learned from the experience of needs assessment that followed the 'internal market' reforms of the 1990s. AIM: To examine general practitioners' (GPs') awareness and experience of needs assessment, to identify barriers to needs assessment in primary care, and to ascertain how better progress might be made in the future. METHOD: A postal questionnaire survey of 1777 Scottish GPs (a one-in-two sample) was combined with a semistructured interview survey of 'lead' GPs from a random sample of 64 mainland Scottish practices between May and August 1996. RESULTS: Sixty-five per cent (1154) of GPs responded to the questionnaire, of which 54% (965) were completed. Over 73% (47) of interviews were completed. Most GPs were unfamiliar with the concept of needs assessment and there was no evidence that needs assessment had influenced commissioning decisions. Most GPs argued that it was not a 'core' activity and that they lacked training in the relevant skills. While the attitude of the majority was indifferent, cynical, and sometimes hostile, a minority, comprising mostly younger fundholders, was more enthusiastic about needs assessment. CONCLUSION: The motivation and attitude of the majority of GPs present a barrier to needs assessment in primary care. GPs will require more resources and training if they are to undertake this responsibility. Most GPs believe than incentives (financial or organisational) will be necessary. Primary care trusts and equivalent structures should be aware of these attitudes as they seek to establish plans based on estimates of population needs in defined locations.

Adult↗
PubMed1999

Randomised trial of personalised computer based information for cancer patients.

OBJECTIVE: To compare the use and effect of a computer based information system for cancer patients that is personalised using each patient's medical record with a system providing only general information and with information provided in booklets. DESIGN: Randomised trial with three groups. Data collected at start of radiotherapy, one week later (when information provided), three weeks later, and three months later. PARTICIPANTS: 525 patients started radical radiotherapy; 438 completed follow up. INTERVENTIONS: Two groups were offered information via computer (personalised or general information, or both) with open access to computer thereafter; the third group was offered a selection of information booklets. OUTCOMES: Patients' views and preferences, use of computer and information, and psychological status; doctors' perceptions; cost of interventions. RESULTS: More patients offered the personalised information said that they had learnt something new, thought the information was relevant, used the computer again, and showed their computer printouts to others. There were no major differences in doctors' perceptions of patients. More of the general computer group were anxious at three months. With an electronic patient record system, in the long run the personalised information system would cost no more than the general system. Full access to booklets cost twice as much as the general system. CONCLUSIONS: Patients preferred computer systems that provided information from their medical records to systems that just provided general information. This has implications for the design and implementation of electronic patient record systems and reliance on general sources of patient information.

Attitude to Computers↗