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Biomedical subjects

A Morgan

Publications and source records attributed to A Morgan.

At least 37 records · Page 2Linked to original sources
PubMed2001

Control of membrane fusion dynamics during regulated exocytosis.

The study of regulated exocytosis uniquely allows the direct measurement of intracellular membrane fusion events in real time. We have exploited this to examine factors that regulate not only the extent but also the dynamics of single fusion/release events. The general strategy used has been to assess exocytosis in transiently transfected PC12 or adrenal chromaffin cells. We aimed to design mutant constructs based on in vitro biochemistry, in some cases informed by knowledge of protein structure. Using this approach we have demonstrated an inhibitory role for the putative Rab3 effector Noc2 that requires interaction with Rab3. Using carbon-fibre amperometry on adrenal chromaffin cells, we have demonstrated regulation of the kinetics of single granule release events consistent with changes in fusion pore dynamics and switches between full fusion and 'kiss-and-run' fusion. These studies have demonstrated a late role for cysteine string protein in exocytosis. In addition, they have focused attention on a key role for Munc18 in the regulation of post-fusion events that affect fusion pore dynamics.

Adrenal Medulla↗
PubMed2001

Ocular blood flow tonometer reproducibility: the effect of operator experience and mode of application.

OBJECTIVE: The purpose of this study was to investigate whether the effect of learning and the reproducibility of measurements varied between the two methods of application (hand-held or slit-lamp mounted) of the ocular blood flow (OBF) tonometer. METHOD: Five consecutive measurements by each method were taken at one examination session on one eye of 35 healthy adults (mean age 36.6 years and range 17-84 years). The subjects were seated for all measures and the sequence of tonometer method was randomised between subjects. RESULTS: A new operator does exhibit a significant learning effect and this learning effect is of a greater magnitude for the hand-held technique. No significant difference was found between methods for pulsatile ocular blood flow (POBF), IOP, pulse amplitude and heart rate. Both methods of application had a high coefficient of reliability for POBF: 0.91 for slit-lamp and 0.89 for hand-held. CONCLUSIONS: We conclude that results from both methods of OBF tonometer application are reliable and either method can be used for clinical and research studies. However it is important that new operators gain sufficient experience with the OBF tonometer to avoid initial operator-induced variability.

Adolescent↗
PubMed2001

Smoking and quitting with the aid of nicotine replacement therapies in the English adult population. Results from the Health Education Monitoring Survey 1995.

BACKGROUND: Many clinical trials have shown the usefulness of nicotine replacement therapies, family physician advice and other cessation aids in enhancing smoking cessation. However, many trials have taken place amongst selected patients and doctors. This paper assesses cessation amongst a representative general adult population in England in order to see whether such aids are as successful amongst more typical smokers. METHODS: Descriptive information on the pattern of smoking cessation aids use in the English population is presented for the first time. This is followed by multivariate probit analysis of the 'Health in England 1995' survey data set in order to predict successful smoking cessation as a function of several variables including use of nicotine gum and patches, willpower, advice from family physicians, social class, education, gender, marital status and family composition. RESULTS: The results tend to confirm that lower social class and lower educational achievement are linked to continuing smoking status. However, users of nicotine gum and patches were found to be less likely to have given up smoking than non-users. This may be explained by the fact that only those who find it difficult to give up will go to the time and expense of considering such aids. These findings could also be explained by the fact that gum and patches have only been available recently in England. The pattern of results also suggests that 'willpower' is a marker for success in cessation as opposed to a determinant of giving up in its own right. CONCLUSION: This research confirms a lot of other research on the determinants of smoking cessation and has for the first time looked at the use and impact of nicotine replacement therapy on giving up in a representative English adult population. More research is needed on observational data sets in order to tease out the true impact of nicotine replacement on cessation rates in representative smoking populations.

Adolescent↗
PubMed2001

Human immunodeficiency virus associated spondyloarthropathy: pathogenic insights based on imaging findings and response to highly active antiretroviral treatment.

The pathogenesis of human immunodeficiency virus (HIV) associated spondyloarthropathy (SpA) is poorly understood. In this case report a patient is described with severe HIV associated reactive arthritis, who on magnetic resonance imaging and sonographic imaging of inflamed knees had extensive polyenthesitis and adjacent osteitis. The arthritis deteriorated despite conventional antirheumatic treatment, but improved dramatically after highly active antiretroviral treatment, which was accompanied by a significant rise in CD4 T lymphocyte counts. The implications of the localisation of pathology and effect of treatment for pathogenic models of SpA and rheumatoid arthritis in the setting of HIV infection are discussed.

Adult↗
PubMed2001

Controlled randomised crossover trial of the effects of physiotherapy on mobility in chronic multiple sclerosis.

OBJECTIVES: To determine whether physiotherapy can improve mobility in chronic multiple sclerosis and whether there is a difference between treatment at home and as a hospital outpatient? METHODS: A randomised controlled crossover trial was undertaken in patients with chronic multiple sclerosis who had difficulty walking and were referred from neurology clinics: allocation was to one of six permutations of three 8 week treatment periods separated by 8 week intervals: treatments consisted of physiotherapy at home, as an outpatient, or "no therapy". The main outcome measures were based on independent assessments at home and included mobility related disability (primary outcome: the Rivermead mobility index), gait impairments, arm function, mood, and subjective patient and carer ratings. Therapy was assessed by recording delivery, achievement of set targets, patient and carer preference, and cost. RESULTS: On the Rivermead mobility index (scale 0-15) (primary outcome) there was a highly significant (p<0.001) treatment effect of 1.4-1.5 units favouring hospital or home based therapy over no therapy: this was supported by other measures of mobility, gait, balance, and the assessor's global "mobility change" score: there was no major difference between home and hospital. Carers preferred home treatment but neither they nor patients discerned greater benefit there. Estimated costs of home physiotherapy were 25 pounds/session and those at hospital were 18 pounds (including 7 pounds patient travel costs). CONCLUSION: A course of physiotherapy is associated with improved mobility, subjective wellbeing, and improved mood in chronic multiple sclerosis compared with no treatment but benefit may only last a few weeks: there is little to choose between home and hospital based therapy but the first is more costly, mainly due to skilled staff travelling time.

Adult↗
PubMed2001

Protective coping: a grounded theory of educative interactions in palliative care nursing.

The development of a workable caring partnership in palliative care between the nurse, patient and informal carer is contingent upon the nurse's use of effective interactions that will not only inform, but also help individuals to work towards common beneficial goals. This article summarizes a research project undertaken in Western Australia, which examined the symbolic nature and characteristics of educative interactions. Their therapeutic value was interpreted in order to construct a theory, which in turn, explained their function. Protective coping, which deals with overcoming or minimizing stressors to the individual, has been identified as a basic social interactional process that is fundamental to the optimization of patients' well being during terminal illness care. An understanding of the knowledge-power relationship in palliative care is crucial if subsequent educative outcomes are to be positively influenced.

Adaptation, Psychological↗
PubMed2000

A direct inhibitory role for the Rab3-specific effector, Noc2, in Ca2+-regulated exocytosis in neuroendocrine cells.

Rab proteins comprise a family of GTPases, conserved from yeast to mammals, which are integral components of membrane trafficking pathways. Rab3A is a neural/neuroendocrine-specific member of the Rab family involved in Ca(2+) -regulated exocytosis, where it functions in an inhibitory capacity controlling recruitment of secretory vesicles into a releasable pool at the plasma membrane. The effector by which Rab3A exerts its inhibitory effect is unclear as the Rab3A effectors Rabphilin and RIM have been excluded from for this role. One putative Rab3A effector in dense-core granule exocytosis is the cytosolic zinc finger protein, Noc2. We have established that overexpression of Noc2 in PC12 cells has a direct inhibitory effect upon Ca(2+)-triggered exocytosis in permeabilized cells. We demonstrate specific nucleotide-dependent binding of Noc2 to Rab3A and show that the inhibition of exocytosis is dependent upon this interaction since Rab3A binding-deficient mutants of Noc2 do not inhibit exocytosis. We propose that Noc2 may be a negative effector for Rab3A in regulated exocytosis of dense-core granules from endocrine cells.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Costs and effectiveness of community postnatal support workers: randomised controlled trial.

OBJECTIVES: To establish the relative cost effectiveness of postnatal support in the community in addition to the usual care provided by community midwives. DESIGN: Randomised controlled trial with six month follow up. SETTING: Recruitment in a university teaching hospital and care provided in women's homes. PARTICIPANTS: 623 postnatal women allocated at random to intervention (311) or control (312) group. INTERVENTION: Up to 10 home visits in the first postnatal month of up to three hours duration by a community postnatal support worker. MAIN OUTCOME MEASURE: General health status as measured by the SF-36 and risk of postnatal depression. Breast feeding rates, satisfaction with care, use of services, and personal costs. RESULTS: At six weeks there was no significant improvement in health status among the women in the intervention group. At six weeks the mean total NHS costs were pound 635 for the intervention group and pound 456 for the control group (P=0.001). At six months figures were pound 815 and pound 639 (P=0.001). There were no differences between the groups in use of social services or personal costs. The women in the intervention group were very satisfied with the support worker visits. CONCLUSIONS: There was no health benefit of additional home visits by community postnatal support workers compared with traditional community midwifery visiting as measured by the SF-36. There were no savings to the NHS over six months after the introduction of the community postnatal support worker service.

Adolescent↗
PubMed2000

Binding of the Epstein-Barr virus major envelope glycoprotein gp350 results in the upregulation of the TNF-alpha gene expression in monocytic cells via NF-kappaB involving PKC, PI3-K and tyrosine kinases.

Epstein-Barr virus (EBV) is a human herpesvirus that interacts with various immunocompetent cells that carry the EBV receptor (CD21/CR2). EBV binds to CR2 through its major envelope glycoprotein 350 (gp350). Previously we had demonstrated that EBV and other human herpesviruses are capable of modulating cytokine synthesis through the deregulated expression of cytokine genes interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and interleukin-2 (IL-2). Here we show that, in contrast to infectious EBV, purified recombinant gp350 upregulates TNF-alpha gene expression in human monocyte/macrophages (M/M) as well as in a monocytoid cell line, U937. Our results also demonstrate that this increased expression is due to both enhanced transcription and stability of TNF-alpha mRNA in gp350-treated cells. The specificity of this effect is evidenced by the fact that pre-incubation of cells with anti-CR2 monoclonal antibody OKB7, which blocks binding of gp350 to CR2, inhibits the above mentioned effects of gp350. Furthermore, we demonstrate that activation of TNF-alpha by gp350 is mediated by NF-kappaB through signal transduction pathways involving PKC, PI3-K and tyrosine kinases. To our knowledge this is the first report describing the modulation of TNF-alpha gene expression by the EBV-gp350 molecule following its interaction with the viral receptor CR2 on cells of the monocytic lineage.

Antibodies, Monoclonal↗
PubMed2000

Significance of atypical glandular cells of undetermined significance on ThinPrep Papanicolaou smears.

OBJECTIVE: The aim of this study was to assess the incidence and risk factors predictive of significant histopathologic findings among women with atypical glandular cells of undetermined significance (AGCUS) on ThinPrep Papanicolaou smears. METHODS: ThinPrep smears with AGCUS obtained between 1997 and 1999 were reviewed. Patients' charts were reviewed and patients' characteristics, follow-up information, and colposcopy and biopsy results were recorded. Pathologic slides were reviewed. The demographic features of women with favor reactive smears were compared with those with favor neoplasia and risk factors predictive of significant histopathologic findings (high-grade squamous intraepithelial lesion, endometrial hyperplasia, and cervical or endometrial cancers) were calculated. RESULTS: The rate of diagnosis of AGCUS was 0.65%. Eighty-four patients with follow-up information were identified. The demographic features of women with smears favor neoplasia (n = 43) were similar to those with smears favor reactive (n = 41). The rates of incidence of any dysplasia or cancer and significant histopathologic findings were 32.1 and 22.6%, respectively, and were higher among women with smears favor neoplasia than among women with smears favor reactive (41.9% versus 22.0%, P = 0.051, and 34.9% versus 9.8%, P = 0.006, respectively). The subtype of cytology was the only factor that predicted significant histopathologic findings (odds ratio = 5.0, 95% confidence interval 1.6, 15.6, P < 0.010). CONCLUSIONS: In women with AGCUS on ThinPrep smears, significant histopathologic findings were found in 34.9% versus 9.8%, depending on the subtype of the smear (favor neoplasia vs reactive). Further studies are needed to validate the cytologic criteria for subtyping AGCUS smears and base management of women with AGCUS cytology on the subtype of the smear.

Adult↗
PubMed2000

Significance of atypical squamous cells of undetermined significance on ThinPrep papanicolaou smears.

OBJECTIVE: The aim of this study was to assess the prevalence and risk factors predictive of dysplasia among women seen in a gynecologic oncology service with the cytologic diagnosis of atypical squamous cells of undetermined significance (ASCUS) on Papanicolaou smears obtained by the ThinPrep method. METHODS: Patients with ASCUS ThinPrep Papanicolaou smears seen at the Division of Gynecologic Oncology, University of Vermont, between 1997 and 1999 were identified. The cytologic smears were reviewed and subtyped into reactive or suggestive of squamous intraepithelial lesion (SIL). The charts of these patients were reviewed and the following information was abstracted: age, gravidity, parity, menopausal status, use of hormonal replacement therapy, smoking, history of pelvic cancer, history of radiation therapy, history of abnormal Papanicolaou smear and its treatment, history of human papillomavirus (HPV) infection, and follow-up information including results of repeat Papanicolaou smears, colposcopy, and biopsies. The prevalence of dysplasia was calculated. The demographic features of women with ASCUS, reactive, were compared with those with ASCUS, SIL, using a two-sample t test, chi(2), and Fisher's exact test. Risk factors predictive of dysplasia were calculated using the odds ratio and the 95% confidence interval. P < 0.05 was considered significant. RESULTS: One hundred twenty-six patients with ASCUS on ThinPrep Papanicolaou smear were identified; 63 patients had ASCUS, reactive, and 63 patients had ASCUS, SIL. The demographic features of both groups were similar. The overall prevalence of dysplasia was 15.9% and was significantly higher among women with ASCUS, SIL, than among women with ASCUS, reactive (25.4% versus 6.4%, P = 0.003). The type of ASCUS cytology (reactive versus SIL), smoking, and history of HPV were significant risk factors for dysplasia (P = 0.003, 0.037, and 0. 042, respectively). CONCLUSIONS: The prevalence of dysplasia among women seen in a gynecologic oncology service with ASCUS cytology on ThinPrep Papanicolaou smears is 15.9%. Women with ASCUS favor SIL, those who smoke, and those with a history of HPV are at higher risk for dysplasia and should be offered colposcopy.

Adult↗
PubMed2000

Non-malignant tracheo-gastric fistula following esophagectomy for cancer.

Two cases of neoesophago-tracheal fistula are described. After esophagectomy for cancer a fistula developed between the trachea and the pulled-up stomach probably because of the ischaemic effect of the tracheostomy tube. At single stage repairs, the fistulae were divided and the gastric defects were closed directly. In one case, tracheal resection and anastomosis was necessary. The defect on the membranous trachea in both cases was patched with an autologous fascia lata graft. A left pectoralis major muscle flap was interposed between the suture lines to prevent recurrence of the fistula. Treatment of this potentially life-threatening and rare condition yielded excellent results.

Esophageal Neoplasms↗
PubMed2000

The role of the fixation location in inhibition of return.

Experiments that have examined inhibition of return (IOR) have typically used trial sequences in which attention is reoriented to a central fixation location between the presentation of the peripheral cue(s) and the target. In examining the role of the fixation location in IOR, three experiments were conducted in which an exogenous cue was used to reorient attention following a peripheral cue and before the appearance of a target. However, this cue occurred at either the traditional central fixation location or a nonfixated location. The results indicate that reorienting attention to a fixated location results in a significant reduction in the inhibitory effect. The results from the study suggest that IOR could serve as a mechanism that improves the efficiency of visual searches.

Attention↗
PubMed2000

The transcriptome of Arabidopsis thaliana during systemic acquired resistance.

Infected plants undergo transcriptional reprogramming during initiation of both local defence and systemic acquired resistance (SAR). We monitored gene-expression changes in Arabidopsis thaliana under 14 different SAR-inducing or SAR-repressing conditions using a DNA microarray representing approximately 25-30% of all A. thaliana genes. We derived groups of genes with common regulation patterns, or regulons. The regulon containing PR-1, a reliable marker gene for SAR in A. thaliana, contains known PR genes and novel genes likely to function during SAR and disease resistance. We identified a common promoter element in genes of this regulon that binds members of a plant-specific transcription factor family. Our results extend expression profiling to definition of regulatory networks and gene discovery in plants.

Arabidopsis↗