Basalioma after amiodarone therapy-not only in Britain.
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Biomedical subjects
Publications and source records attributed to M A Hall.
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In etiolated seedlings of Pisum sativum and leaves of Arabidopsis thaliana, in vivo ethylene treatment resulted in an increase in in vitro phosphorylation of 17 kD (P. sativum) or 16 and 17 kD (A. thaliana) polypeptides. These polypeptides were identified as nucleoside diphosphate kinase (NDPK) based on both biochemical properties and interaction with antibodies against NDPK from P. sativum. Using the receptor-directed antagonist of ethylene action 2,5-norbornadiene and the ethylene-insensitive mutants of A. thaliana etr1-1 and eti5, ethylene specificity and receptor dependence of NDPK phosphorylation have been demonstrated. In pea epicotyls, ethylene treatment also led to increase in nucleoside transferase activity unlike in A. thaliana leaves. The increases in nucleoside transferase activity and NDPK phosphorylation were very rapid and transient. The results suggest a role for NDPK as a possible component of the ethylene signal transduction chain.
BACKGROUND: Over the past decade more than 120 advanced neonatal nurse practitioners (ANNPs) have graduated from the Southampton based ANNP programme. OBJECTIVES: To determine the scope of practice and evolving role of ANNPs and to identify factors that may affect future recruitment and retention. METHOD: An open ended structured questionnaire on clinical role, working arrangements, retention and attrition, continuing education, and professional development was sent to 95 ANNPs. RESULTS: A response rate of 83% was achieved. There was an attrition rate of 14%, with most ANNPs remaining in their original seconding unit. Factors considered to be important for role satisfaction included a well defined role, working within a team of ANNPs, appropriate remuneration, and evidence of unit support for both role definition and continuing professional development. CONCLUSIONS: Although ANNPs are expensive to both train and employ, this evidence suggests that there is a good return on the investment in terms of retention to the unit and the specialty. Their role incorporates many features of advanced nursing practice as well as providing "value added" neonatal care by merging traditional medical and nursing roles and crossing professional boundaries. In 2004 the manpower challenges for neonatal units will be even more acute; these data confirm that there are effective options available but they require long term strategic planning and investment.
Lymphocyte subpopulation levels are used for prognosis and monitoring of a variety of human diseases, especially those with an infectious etiology. As a primary step to defining the major gene variation underlying these phenotypes, we conducted the first whole-genome screen for quantitative variation in lymphocyte count, CD4 T cell, CD8 T cell, B cell, and natural killer cell numbers, as well as CD4:CD8 ratio. The screen was performed in 15 of the CEPH families that form the main human genome genetic project mapping resource. Quantitative-trait loci (QTLs) that account for significant proportions of the phenotypic variance of lymphocyte subpopulations were detected on chromosomes 1, 2, 3, 4, 8, 9, 11, 12, and 18. The most significant QTL found was for CD4 levels on chromosome 8 (empirical P=.00005). Two regions of chromosome 4 showed significant linkage to CD4:CD8 ratio (empirical P=.00007 and P=.003). A QTL for the highly correlated measures of CD4 and CD19 levels colocalized at 18q21 (both P=.003). Similarly, a shared region of chromosome 1 was linked to CD8 and CD19 levels (P=.0001 and P=.002, respectively). Several of the identified chromosome regions are likely to harbor polymorphic candidate genes responsible for these important human phenotypes. Their discovery has important implications for understanding the generation of the immune repertoire and understanding immune-system homeostasis. More generally, these data show the power of an integrated human gene-mapping approach for heritable molecular phenotypes, using large pedigrees that have been extensively genotyped.
Waikato Environment for Knowledge Analysis (WEKA) is a comprehensive suite of Java class libraries that implement many state-of-the-art machine learning/data mining algorithms. Non-programmers interact with the software via a user interface component called the Knowledge Explorer. Applications constructed from the WEKA class libraries can be run on any computer with a web-browsing capability, allowing users to apply machine learning techniques to their own data regardless of computer platform. This paper describes the user interface component of the WEKA system in reference to previous applications in the predictive modelling of foods.
OBJECTIVE: To examine the clinical and functional outcome of adults with juvenile idiopathic arthritis (JIA) using the recent World Health Organization/International League Against Rheumatism (ILAR) classification. PATIENTS AND METHODS: Two hundred and fifty-nine adults with long-standing JIA (average disease duration 28.3 yr) were eligible for the study; 246 (95%) attended for an interview, clinical examination and notes review and 231 (89.2%) returned a comprehensive functional and psychosocial self-assessment questionnaire. RESULTS: Of all patients, 43.3% had active arthritis clinically and 54.4% on laboratory measures (C-reactive protein). Clinical inflammation was less common in systemic-onset JIA. The percentage of all patients with severe disability (Health Assessment Questionnaire score >1.5) was 42.9. Uveitis occurred frequently in the oligoarticular-onset and enthesitis-related subsets. Over 30% of the extended oligoarticular group with uveitis developed glaucoma compared with none of the enthesitis group. CONCLUSIONS: Adults with JIA often have significant levels of disability, often related to continuing active disease over prolonged periods. There is a clear need for good transition from paediatric to high-quality adult rheumatology care.
OBJECTIVE: To examine the levels of education and employment in adults with juvenile idiopathic arthritis (JIA) compared with their siblings and national figures. PATIENTS AND METHODS: Two hundred and forty-six adults identified with long-standing JIA had an average disease duration of 28.3 yr. Educational achievements and employment status were recorded and comparative data obtained from siblings and the National Office for Statistics, UK. The effects, incidence and nature of discrimination in the workplace were also explored. RESULTS: Across all levels of education the study group achieved significantly better results than both the national average and their siblings. In contrast, the rate of unemployment in the patient group was more than twice that in the national population. The percentage of patients who had encountered discrimination in the workplace was 25.1.
OBJECTIVE: To examine social function, relationships and sexual activity in adults with juvenile idiopathic arthritis (JIA). PATIENTS AND METHODS: Two hundred and forty-six adults identified with long-standing JIA had an average disease duration of 28.3 yr. Specific information was sought on marital status, offspring, age at first sexual encounter, and problems related to disease in sexual activity and pregnancy. RESULTS: Fewer patients (42.8%) were in stable relationships than their siblings (55.3%). The percentage of patients with children was 27.5. Twenty-three per cent of all known pregnancies ended in miscarriage. Of the women who had had a Caesarean, 78.9% had either reduced hip mobility or short stature. JIA had a detrimental effect on body image in 50.7% of patients but relationships were affected in only 28.2%. The percentage of patients who were sexually active or had had previous sexual experience was 83.3; 58.3% of these had disease-related sexual problems. CONCLUSIONS: A significant proportion of individuals are sexually active before transfer to adult rheumatology care at the age of 18 yr. This highlights the need to introduce sexual counselling in adolescent clinics. The high incidence of psychological sexual problems may benefit from appropriate counselling and training.
OBJECTIVE: To examine the predictive factors for anxiety, depression and pain in adults with juvenile idiopathic arthritis (JIA). PATIENTS AND METHODS: Two hundred and forty-six adults identified with long-standing JIA had an average disease duration of 28.3 yr. Candidate factors potentially predictive for pain, anxiety and depression were assessed by multiple regression analysis. RESULTS: Of the patients, 31.6% were anxious, 5.2% were depressed, and 21.1% had previously suffered from depression. The percentage of the variance accounted for by other variables was 78.8 for anxiety variance and 54.5 for depression, but there was little influence from physical disease-related factors. Severe pain, measured on a visual analogue scale, occurred in 32.9% of patients, and 22.8% had poor perceived control over their pain. Function, coping strategies, pain self-efficacy, inflammation and previous depression could predict 39.6% of the variance in pain. CONCLUSIONS: Comparing adults with children, disease activity and control over pain remain predictors of pain but become less important than disability and coping strategies.
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Climate models with increased levels of carbon dioxide predict that global warming causes heating in the tropics, but investigations of ancient climates based on palaeodata have generally indicated cool tropical temperatures during supposed greenhouse episodes. For example, in the Late Cretaceous and Eocene epochs there is abundant geological evidence for warm, mostly ice-free poles, but tropical sea surface temperatures are generally estimated to be only 15-23 degrees C, based on oxygen isotope palaeothermometry of surface-dwelling planktonic foraminifer shells. Here we question the validity of most such data on the grounds of poor preservation and diagenetic alteration. We present new data from exceptionally well preserved foraminifer shells extracted from impermeable clay-rich sediments, which indicate that for the intervals studied, tropical sea surface temperatures were at least 28-32 degrees C. These warm temperatures are more in line with our understanding of the geographical distributions of temperature-sensitive fossil organisms and the results of climate models with increased CO2 levels.
Current progress on the mechanisms of ethylene signal perception and transduction are reviewed with an emphasis on reconciling data from molecular genetics and from biochemical approaches. It is proposed that there exist two or more interacting transduction pathways.
The adaptive immune system in mammals acts in a coordinated manner to eliminate environmentally derived pathogens. Humans, mice and rats show within species variation in the levels and ratios of their peripheral CD4+ and CD8+ T cells and to a significant degree this variation is under the control of polymorphic genes. Whether genes act separately to specify CD4+ and CD8+ subpopulation levels or whether CD8+ variation is controlled through gene and environmental action on CD4+ cells or vice versa, is not known. We use a quantitative modelling approach in identical and non-identical female human twins to delineate the lines of control which act upon and between CD4+ and CD8+ subsets. The major findings of the study are: (1) genetic variation controls CD8+ T cell levels through two major routes-the first is via an effect on CD4+ T cells which accounts for the observed co-variation between CD4+ and CD8+ T cells, the second is through direct action on CD8+ T cell levels. (2) No evidence of a gene effect from CD8+ T cells on CD4+ cells is observed. Our findings have implications for the evolution of the complex defence system of which CD4+ and CD8+ T cells are a crucial part and encourage further work towards locating common pleiotropic quantitative trait loci responsible for variation in numbers of T cells.
Despite the profound and pervasive importance of trust in medical settings, there is no commonly shared understanding of what trust means, and little is known about what difference trust actually makes, what factors affect trust, and how trust relates to other similar attitudes and behaviors. To address this gap in understanding, the emerging theoretical, empirical, and public policy literature on trust in physicians and in medical institutions is reviewed and synthesized. Based on this review and additional research and analysis, a formal definition and conceptual model of trust is presented, with a review of the extent to which this model has been confirmed by empirical studies. This conceptual and empirical understanding has significance for ethics, law, and public policy.
Interleukin-11 (IL-11) is a member of the gp130 family of cytokines. These cytokines drive the assembly of multisubunit receptor complexes, all of which contain at least one molecule of the transmembrane signaling receptor gp130. IL-11 has been shown to induce gp130-dependent signaling through the formation of a high affinity complex with the IL-11 receptor (IL-11R) and gp130. Site-directed mutagenesis studies have identified three distinct receptor binding sites of IL-11, which enable it to form this high affinity receptor complex. Here we present data from immunoprecipitation experiments, using differentially tagged forms of ligand and soluble receptor components, which show that multiple copies of IL-11, IL-11R, and gp130 are present in the receptor complex. Furthermore, it is demonstrated that sites II and III of IL-11 are independent gp130 binding epitopes and that both are essential for gp130 dimerization. We also show that a stable high affinity complex of IL-11, IL-11R, and gp130 can be resolved by nondenaturing polyacrylamide gel electrophoresis, and its composition verified by second dimension denaturing polyacrylamide gel electrophoresis. Results indicate that the three receptor binding sites of IL-11 and the Ig-like domain of gp130 are all essential for this stable receptor complex to be formed. We therefore propose that IL-11 forms a hexameric receptor complex composed of two molecules each of IL-11, IL-11R, and gp130.
Protein kinase activity was studied in cytosolic extracts from leaves of wild type Arabidopsis thaliana, the ethylene-insensitive mutant, etr1, and the constitutive triple-response mutant, ctr1. Treatment of wild type with ethylene resulted in increased myelin basic protein (MBP) phosphorylation. In etr1, constitutive protein kinase activity was lower than in wild type, but in ctr1, activity was enhanced. A protein of M(r) approximately 47 kDa associated with MBP-phosphorylating activity was detected using in gel protein kinase assays and phosphorylation of this protein was promoted by ethylene treatment in wild type while activity in the mutants reflected that of MBP phosphorylation. Both MAPKinase (ERK 1) and phosphotyrosine antibodies immunoprecipitated MBP-phosphorylating activity and detected a polypeptide band at M(r) approximately 47 kDa. Immunoprecipitated MBP-phosphorylating activity was again much lower in etr1 compared to wild type but much higher in ctr1. Antibodies to phosphorylated MAPKinase recognised proteins at approximately 47 kDa and the signal was upregulated in response to ethylene. The data obtained suggest that the detected protein(s) is a MAPKinase and provide further evidence confirming that a MAPKinase cascade(s) is involved in ethylene signal transduction.
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