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Biomedical subjects

J Harrison

Publications and source records attributed to J Harrison.

At least 55 records · Page 3Linked to original sources
PubMed2000

Identification of multiple cis-acting elements mediating the induction of prostaglandin G/H synthase-2 by phorbol ester in murine osteoblastic cells.

The tumor promoter phorbol 13-myristate 12-acetate (PMA), the best characterized protein kinase C agonist, frequently regulates gene expression via activation of Fos/Jun (AP-1) complexes. PMA rapidly and transiently induces prostaglandin G/H synthase-2 (PGHS-2) expression in murine osteoblastic MC3T3-E1 cells, but no functional AP-1 binding motifs in the 5'-flanking region have been identified. In MC3T3-E1 cells transfected with -371/+70 bp of the PGHS-2 gene fused to a luciferase reporter gene (Pluc), PMA stimulates luciferase activity up to eightfold. Computer analysis of the sequence of the PGHS-2 promoter region identified three potential AP-1 elements in the -371/+70 bp region, and deletion analysis suggested that the sequence 5'-aGAGTCA-3' at -69/-63 bp was most likely to mediate stimulation by PMA. Mutation of the putative AP-1 sequence reduces the ability of PMA to stimulate Pluc activity by 65%. On electrophoretic mobility shift analysis (EMSA), PMA induces binding to a PGHS-2 probe spanning this sequence, binding is blocked by an unlabeled AP-1 canonical sequence, and antibodies specific for c-Jun and c-Fos inhibit binding. Mutation of this AP-1 site also causes a small (22%) but significant reduction in the serum stimulation of Pluc activity in transiently transfected MC3T3-E1 cells. On EMSA, serum induces binding to a PGHS-2 probe spanning the AP-1 site, binding is blocked by an unlabeled AP-1 canonical sequence, and antibodies specific for c-Jun and c-Fos inhibit binding. Joint mutation of this AP-1 site and the nearby CRE site at -56/-52 bp, previously shown to mediate serum, v-src and PDGF induction of PGHS-2 in NIH-3T3 cells, blocks both PMA and serum induction of Pluc activity in MC3T3-E1 cells. Hence, the AP-1 and CRE binding sites are jointly but differentially involved in both the PMA and serum stimulation of PGHS-2 promoter activity.

3T3 Cells↗
PubMed2000

Helicobacter pylori and the learning disabled.

Those with a learning disability previously cared for in institutions have now been discharged into smaller community homes. This has meant that an increased burden has been placed on general practitioners (GPs) to evaluate and treat those who have symptoms that may be difficult to interpret. This report presents the prevalence of Helicobacter pylori in those still awaiting discharge and discusses the possible symptoms that GPs may encounter.

Adolescent↗
PubMed1999

Integration of microfabricated devices to capillary electrophoresis-electrospray mass spectrometry using a low dead volume connection: application to rapid analyses of proteolytic digests.

This report describes the development of a compact and versatile, micromachined chip device enabling the efficient coupling of capillary electrophoresis to electrospray mass spectrometry (CE-ESMS). On-chip separation provides a convenient means of achieving rapid sample cleanup and resolution of multicomponent samples (typically 2-5 min) prior to mass spectral analysis. A low dead volume connection facilitating the coupling of microfabricated devices to CE-ESMS was evaluated using two different interfaces. The first configuration used disposable nanoelectrospray emitters directly coupled to the chip device via this low dead volume junction, thereby providing rapid separation of complex protein digests. The performance of this interface was compared with that of more traditional configurations using a sheath flow CE-ESMS arrangement where a fused-silica capillary of varying length enabled further temporal resolution of the multicomponent samples. The sensitivity and analytical characteristics of these interfaces were investigated in both negative and positive ion modes using standard peptide mixtures. The separation performance for synthetic peptides using a chip coated with amine reagent ranged from 26,000 to 58,000 theoretical plates for a sheath flow CE-ESMS interface comprising a 15-cm CE column. Replicate injections of a dilution series of peptide standards provided detection limits of 45-400 nM without the use of on-line preconcentration devices. The reproducibility of migration time ranged from 0.9 to 1.5% RSD whereas RSDs of 5-10% were observed on peak areas. The application of these devices for the analysis of protein digests was further evaluated using on-line tandem mass spectrometry.

Amino Acid Sequence↗
PubMed1999

beta Blockade after myocardial infarction: systematic review and meta regression analysis.

OBJECTIVES: To assess the effectiveness of beta blockers in short term treatment for acute myocardial infarction and in longer term secondary prevention; to examine predictive factors that may influence outcome and therefore choice of drug; and to examine the clinical importance of the results in the light of current treatment. DESIGN: Systematic review of randomised controlled trials. SETTING: Randomised controlled trials. SUBJECTS: Patients with acute or past myocardial infarction. INTERVENTION: beta Blockers compared with control. MAIN OUTCOME MEASURES: All cause mortality and non-fatal reinfarction. RESULTS: Overall, 5477 of 54 234 patients (10.1%) randomised to beta blockers or control died. We identified a 23% reduction in the odds of death in long term trials (95% confidence interval 15% to 31%), but only a 4% reduction in the odds of death in short term trials (-8% to 15%). Meta regression in long term trials did not identify a significant reduction in effectiveness in drugs with cardioselectivity but did identify a near significant trend towards decreased benefit in drugs with intrinsic sympathomimetic activity. Most evidence is available for propranolol, timolol, and metoprolol. In long term trials, the number needed to treat for 2 years to avoid a death is 42, which compares favourably with other treatments for patients with acute or past myocardial infarction. CONCLUSIONS: beta Blockers are effective in long term secondary prevention after myocardial infarction, but they are underused in such cases and lead to avoidable mortality and morbidity.

Adrenergic beta-Antagonists↗
PubMed1999

Trends in hospital efficiency among metropolitan markets.

This study evaluates trends in efficiency among American hospital markets. A total of 6010 hospitals were identified for use in the analysis from the American Hospital Association's Annual Surveys for 1989 and 1993. Using data envelopment analysis (DEA), a longitudinal study of hospital efficiency was conducted on all 314 metropolitan markets in the United States. Results suggest that large hospital markets generally demonstrated higher inefficiency. The major inefficiencies exist in the availability of hospital services, the number of operating beds, the utilization of hospital staffing and operating expenses. Consequently, the large hospital market had a significant excess of health manpower that resulted in inefficiency that amounted to approximately $23 billion. From a policy perspective, this study has shed some light on the need to establish more specific policies to address inefficiency in the health care industry.

American Hospital Association↗
PubMed1999

The management of occupational health by NHS Trusts in the north of England.

This paper reports the findings of an audit of the management of occupational health arrangements in 36 NHS Trusts in the Northern and Yorkshire region of England. A questionnaire was designed based on a national NHS occupational health standard to obtain data on eight categories of occupational health activity: health and safety; pre-employment assessments; Infection Control; health surveillance; sickness absence; ill-health retirement; health promotion and record storage. The management arrangements for occupational health were varied. Assessments of workplace hazards, prevention of HIV-positive workers from performing exposure-prone invasive procedures and the assessment of pregnant workers were identified as issues for further consideration. Provision of competent and effective occupational health services will assist in the management of sickness absence and in the protection and promotion of health of staff. It will also contribute to the health and safety of patients.

England↗
PubMed1999

Social determinants of GHQ score by postal survey.

BACKGROUND: To develop interventions to reduce the morbidity associated with depression and anxiety, more information is needed about the social and demographic determinants of these disorders and the relative contributions of different potential predictors. METHODS: Using stratified sampling from the Family Health Services Authority (FHSA) register, postal surveys were sent to 61,000 adults across the North Western Regional Health Authority. Psychological morbidity was assessed using the 12-item General Health Questionnaire (GHQ). Nine potential predictors of morbidity were rated, including socio-demographic details and the presence of longstanding limiting physical illness and of a confidante. Logistic regression analyses were used to consider each of the nine potential predictors separately and in combination. RESULTS: A total of 38,014 questionnaires were returned (63 per cent). After adjustment for all other variables the strongest predictors of a high GHQ score were the absence of a confidante (odds ratio (OR) 3.64), longstanding limiting physical illness (OR 2.93), unemployment (OR 1.91), being a student (OR 1.78), being female (OR 1.64), single parenthood (OR 1.55) and living alone (OR 1.32). GHQ scores were highest in the 18-34 age range. Ethnicity exerted no significant effect after adjustment for other variables. CONCLUSION: In keeping with other research the data suggest that sociodemographic factors are strong predictors of depression and anxiety. The most vulnerable population groups are those with longstanding limiting physical illness and no-one to talk to. This should help in identifying high-risk individuals and informing preventive strategies.

Adolescent↗
PubMed1998

Combinatorial signaling codes for the progressive determination of cell fates in the Drosophila embryonic mesoderm.

Mesodermal progenitors arise in the Drosophila embryo from discrete clusters of lethal of scute (l'sc)-expressing cells. Using both genetic loss-of-function and targeted ectopic expression approaches, we demonstrate here that individual progenitors are specified by the sequential deployment of unique combinations of intercellular signals. Initially, the intersection between the Wingless (Wg) and Decapentaplegic (Dpp) expression domains demarcate an ectodermal prepattern that is imprinted on the adjacent mesoderm in the form of a L'sc precluster. All mesodermal cells within this precluster are competent to respond to a subsequent instructive signal mediated by two receptor tyrosine kinases (RTKs), the Drosophila epidermal growth factor receptor (DER) and the Heartless (Htl) fibroblast growth factor receptor. By monitoring the expression of the diphosphorylated form of mitogen-associated protein kinase (MAPK), we found that these RTKs are activated in small clusters of cells within the original competence domain. Each cluster represents an equivalence group because all members initially resemble progenitors in their expression of both L'sc and mesodermal identity genes. Thus, localized RTK activity induces the formation of mesodermal equivalence groups. The RTKs remain active in the single progenitor that emerges from each cluster under the subsequent inhibitory influence of the neurogenic genes. Moreover, DER and Htl are differentially involved in the specification of particular progenitors. We conclude that distinct cellular identity codes are generated by the combinatorial activities of Wg, Dpp, EGF, and FGF signals in the progressive determination of embryonic mesodermal cells.

Animals↗
PubMed1998

Mental health in the north west region of England: associations with deprivation.

Minor psychiatric morbidity is known to be associated with social disadvantage, but few studies have explored this association at the population level. This study reports data from a postal survey across 19 health districts in one region, with a total sample of 38,000 respondents. The percentage scoring above the General Health Questionnaire (GHQ) threshold for each health district was correlated with measures of deprivation derived from the 1991 census and standardised mortality ratios. Highly significant correlations were seen between the percentage above the GHQ threshold and the Underprivileged Area (UPA) score (r = 0.84), under 65 Standardised Mortality Ratio (SMR; r = 0.80), lack of amenities (r = 0.56), overcrowding (r = 0.54), lone-parent families (r = 0.84), unemployment (r = 0.87), unskilled workers (r = 0.77), ethnic minority composition (r = 0.58) and social mobility (r = 0.85). However, the three most deprived districts had the lowest response rates and when these were excluded from the analysis, only the correlations with under 65 SMR (r = 0.57, P < 0.05), UPA score (r = 0.52, P < 0.05) and unskilled workers (r = 0.60, P < 0.05) remained significant. There may be a threshold effect for the impact of social disadvantage on mental health, with much higher rates of psychological morbidity among markedly disadvantaged populations.

Adult↗
PubMed1998

Saccadic eye movement and working memory deficits following damage to human prefrontal cortex.

A patient with a lesion confined largely to the right inferior frontal gyrus was found to be impaired on tests of spatial working memory and executive functioning. By contrast, his pattern recognition was good. The patient's selective impairments are consistent with the view that prefrontal cortex contributes to processes involved in spatial working memory. The patient was also tested on a range of oculomotor paradigms, some of which required the temporary suppression of a saccadic response. He was unable to suppress making contra- or ipsilesional reflexive glances to peripheral stimuli on the "anti-saccade" paradigm, but his performance improved on delayed saccade, memory-guided saccade and fixation tasks. Although reflexive glances were observed under these conditions they occurred more frequently in response to contralesional stimuli than ipsilesional ones. Furthermore, the patient had no difficulty in performing anti-point movements with his ipsilesional hand. Thus, his inability to suppress reflexive glances on the anti-saccade task is not due to a generalised problem of "distractibility". The patient's deficits are discussed in terms of models of anti-saccade generation and are related to recent findings regarding the role of prefrontal cortex in working memory and visual attention.

Attention↗
PubMed1998

Irritant contact dermatitis due to 1-bromo-3-chloro-5,5-dimethylhydantoin in a hydrotherapy pool. Risk assessments: the need for continuous evidence-based assessments.

A physiotherapist working in hydrotherapy presented to occupational health with irritant contact dermatitis. Subsequent investigation revealed that the likely causative agent was 1-bromo 3-chloro 5,5 dimethylhydantoin which was used to disinfect the hydrotherapy pool. A COSHH risk assessment had been performed which failed to take full account of current knowledge and this agent had been introduced into the workplace. The development of adverse health effects among staff and other pool users lead to a review of this risk assessment and eventually a return to less hazardous chlorine-based disinfection. Had an evidence-based approach been combined with an appropriate COSHH assessment prior to and following changes in the workplace then unnecessary risk to employees would not have occurred.

Dermatitis, Contact↗