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D Edwards

Publications and source records attributed to D Edwards.

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

Expression level-dependent contribution of glucocorticoid receptor domains for functional interaction with STAT5.

The action of the glucocorticoid receptor (GR) on beta-casein gene transcription serves as a well-studied example of a case where the action of the GR is dependent on the activity of another transcription factor, STAT5. We have investigated the domain-requirement of the GR for this synergistic response in transfection experiments employing GR mutants and CV-1 or COS-7 cells. The results were influenced by the expression levels of the GR constructs. At low expression, STAT5-dependent transactivation by mutants of the GR DNA binding domain or N-terminal transactivation domain was impaired and the antiglucocorticoid RU486 exhibited a weak agonistic activity. When the N-terminal region of the GR was exchanged with the respective domain of the progesterone receptor, STAT5-dependent transactivation was reduced at low and high expression levels. Only at high expression levels did the GR exhibit the properties of a coactivator and enhanced STAT5 activity in the absence of a functional DNA binding domain and of GR binding sites in the proximal region of the beta-casein gene promoter. Furthermore, at high GR expression levels RU486 was nearly as efficient as dexamethasone in activating transcription via the STAT5 dependent beta-casein gene promoter. The results reconcile the controversial issue regarding the DNA binding-independent action of the GR together with STAT5 and provide evidence that the mode of action of the GR depends not only on the type of the particular promoter at which it acts but also on the concentration of the GR. GR DNA binding function appears to be mandatory for beta-casein gene expression in mammary epithelial cells, since the promoter function is completely dependent on the integrity of GR binding sites in the promoter.

Amino Acid Sequence↗
PubMed2001

Tourniquet-induced wound hypoxia after total knee replacement.

We have investigated whether the thigh tourniquet used during total knee replacement (TKR) influenced the development of postoperative wound hypoxia and was a cause of delayed wound healing. We allocated randomly 31 patients (31 TKRs) to one of three groups: 1) no tourniquet; 2) tourniquet inflated at low pressure (about 225 mmHg); and 3) tourniquet inflated to high pressure of about 350 mmHg. Wound oxygenation was measured using transcutaneous oxygen electrodes. In the first week after surgery, patients with a tourniquet inflated to a high pressure had greater wound hypoxia than those with a low pressure. Those without a tourniquet also had wound hypoxia, but the degree and duration were less pronounced than in either of the groups with a tourniquet. Use of a tourniquet during TKR can increase postoperative wound hypoxia, especially when inflated to high pressures. Our findings may be relevant to wound healing and the development of wound infection.

Arthroplasty, Replacement, Knee↗
PubMed2000

p53 checkpoint-defective cells are sensitive to X rays, but not hypoxia.

X-ray-induced damage leads to cell-cycle "checkpoint" arrest by p53-dependent induction of the cyclin-dependent kinase inhibitor p21 (Waf1/Cip1/Sdi1). Human tumor cells that lack this response fail to arrest after exposure to DNA-damaging agents, undergo multiple rounds of endoreduplicative DNA synthesis, and eventually commit to an apoptotic cell death. Since low oxygen tension can also induce p53 protein accumulation, and can lead to cell-cycle arrest or apoptosis, we examined the expression of p21 in tumor cells under normoxic and hypoxic conditions. In a survey of cells, mRNA for the p21 gene was induced two- to threefold in response to hypoxia in a seemingly p53-independent manner. We therefore examined genetically matched cells that differ in their p21 and p53 status for response to ionizing radiation and hypoxia. We found that both p21-deficient and p53-deficient cells exhibit an increase in chromosome instability, an increased level of apoptosis, and a failure to arrest after exposure to ionizing radiation. However, cells that lack either p21 or p53 exhibit no increase in chromosome instability or elevated apoptosis and still arrest in response to hypoxia. Thus, the mechanism responsible for the differential response to either hypoxia or X rays presumably lies in the control of cell-cycle progression in response to stress and its dependence on p21. Since the loss of a DNA-damage-dependent checkpoint does not sensitize cells to killing by stresses that elicit a DNA-damage-independent checkpoint, targeting the function of p21 pharmacologically will not kill tumor cells in situ in the absence of a DNA damage signal.

Apoptosis↗
PubMed2000

The role of mid-palaeozoic mesofossils in the detection of early bryophytes.

Recently discovered Silurian and Devonian coalified mesofossils provide an additional source of data on early embryophytes. Those reviewed in this paper are considered of some relevance to understanding the early history of bryophytes while highlighting the difficulties of recognizing bryophytes in often very fragmentary fossils. The first group comprises sporophytes in which terminal sporangia contain permanent dyads and tetrads. Such spores (cryptospores) are similar to those found dispersed in older Ordovician and Silurian strata, when they are considered evidence for a land vegetation of embryophytes at a bryophyte grade. The phylogenetic significance of plants, where the axes associated with both dyad- and tetrad-containing sporangia are branching, a character state not found in extant bryophytes, is discussed. The second group comprises axial fossils, many with occasional stomata, in which central conducting strands include G-type tracheids and a number of novel types of elongate elements not readily compared with those of any tracheophyte. They include smooth-walled, evenly thickened elongate elements as well as those with numerous branching +/- anastomosing projections into the lumen. Some of the latter bear an additional microporate layer, but the homogenized lateral walls between adjacent cells are never perforate. Such cells, which occur in various combinations in central strands, are compared with the leptoids and hydroids of mosses, hydroids of liverworts and presumed water-conducting cells in coeval Lower Devonian plants such as Aglaophyton. It is concluded that lack of information on the chemistry of their walls hampers sensible assessment of their functions and the affinities of the plants. Finally, a minute fossil, comprising an elongate sporangium in which a central cylindrical cavity containing spores and possible elaters terminates in a complex poral dehiscence apparatus, is used to exemplify problems of identifying early bryophytes. It is concluded that further progress necessitates the discovery of pre-Upper Silurian fossils with well-preserved anatomy, as well as a re-evaluation of criteria used to assess existing and new Devonian fossils for bryophyte affinity.

Biological Evolution↗
PubMed2000

Formula for surgical practice resuscitation in an academic medical center.

BACKGROUND: Managing patient referrals for surgical consultation in an academic practice has traditionally emphasized clinical rather than service expertise. However, assuring both efficiency and accuracy in the initial consultation have become critical early measures of quality care. METHODS: In partnership with the academic medical center administration, current practice was analyzed. Performance and communication standards were established around an ideal patient experience. A new ambulatory consultation process was developed; and flowcharting methods for resource allocation, statistical process control, and pre-visit data collection were used to reduce patient administrative time. Automated referral reports engaged referring physicians throughout the consultation. RESULTS: Accurate insurance and referral authorization have been provided for all patients, including the 4% who are underinsured. Patient, provider, and referring physician satisfaction has increased significantly. Staff time investment has progressively declined from 52 +/- 11 (95% confidence) minutes to 34 +/- 10 minutes for most patients. Realignment of tasks has reduced the administrative time spent by the patient by 32% without compromising clinical time. New patient volume increased by 29% per year, maintaining regional market share. CONCLUSIONS: Expertise in the process of consultation delivery is feasible and will be increasingly critical to the survival of academic surgical practice in a competitive market.

Academic Medical Centers↗
PubMed2000

From fold recognition to homology modeling: an analysis of protein modeling challenges at different levels of prediction complexity.

An analysis of different approaches to protein structure prediction is presented based solely on the range of models submitted to the third Critical Assessment of Protein Structure Prediction (CASP3) conference. CASP conferences evaluate the current state of the art of protein structure prediction by comparing blind prediction efforts of many groups for the same set of target sequences. Target sequences may be highly similar to those with known structure or can be totally (at least superficially) sequentially dissimilar. Techniques applied to those blind predictions (over 40 targets) ranges from a detailed homology prediction to the detection of remote homologues well below a twilight zone of protein sequence similarity. For the CASP3 conference, we have submitted predictions, totaling 35, with various levels of difficulty and complexity. For ten submitted homology targets, eight of them were determined by experiment so far. The RMSD of C-alpha atoms are 1.2-1.7, 2.3, and 4.6-17.9 A for the three easy targets, two hard targets, and three very hard homology targets, respectively. Out of 18-fold recognition predictions available for analysis, we got six correct predictions, five near misses, three tough near misses and four far misses. Here we analyze successes and failures of those predictions in an attempt to identify common problems and common achievements.

Computer Simulation↗
PubMed2000

Stress and burnout in community mental health nursing: a review of the literature.

There is a growing body of evidence that suggests that many community mental health nurses (CMHNs) experience considerable stress and burnout. This review aimed to bring together the research evidence in this area for CMHNs working within the UK. Seventeen papers were identified in the literature, seven of which looked at stress and burnout for all members of community mental health teams (CMHTs) and the remaining 10 papers focused on CMHNs. The evidence indicates that those health professionals working as part of community teams are experiencing increasing levels of stress and burnout as a result of increasing workloads, increasing administration and lack of resources. For CMHNs specific stressors were identified. These included increases in workload and administration, time management, inappropriate referrals, safety issues, role conflict, role ambiguity, lack of supervision, not having enough time for personal study and NHS reforms, general working conditions and lack of funding and resources. Areas for future research are described and the current study of Welsh CMHNs is announced. This review has been completed against a background of further significant changes in the health service. In the mental health field, specific new initiatives will have a significant impact on the practice of community mental health nursing. A new National Framework for Mental Health, along with a review of the Mental Health Act (1983), will undoubtedly help to shape the future practice of mental health nursing.

Burnout, Professional↗
PubMed2000

Burnout in community mental health nurses: findings from the all-Wales stress study.

Stress and its outcomes are significant problems for mental health workers. Questionnaires were sent to 614 community mental health nurses (CMHNs) in Wales. Three hundred and one responded (49%). Of these, 283 completed the Maslach Burnout Inventory (MBI) (Maslach et al. 1996). Half of those who responded indicated that they were emotionally overextended and exhausted by their work. One quarter of respondents were found to possess negative attitudes towards their clients, and approximately one in seven experienced little or no sense of satisfaction with their work. Working in an urban environment and lacking a supportive line manager were indicators for higher emotional exhaustion. CMHNs were significantly more likely to have negative attitudes towards their clients if they: were male; worked with an elderly care caseload; lacked job security; and had an unsupportive line manager. However, CMHNs who had worked longer within the field of community mental health were more likely to have positive attitudes towards their clients. Those CMHNs who had not completed a specialist postqualifying education course and those who did not hold a supervisory or management position were found to have a lowered sense of personal satisfaction in their work. Those CMHNs who reported that they drank alcohol were more satisfied with their sense of personal accomplishments achieved in their work.

Adult↗
PubMed2000

Self-esteem in community mental health nurses: findings from the all-Wales stress study.

The authors conducted an all-Wales survey of community mental health nurses (CMHNs) to determine their levels of stress, coping and burnout. A total of 301 CMHNs were surveyed in 10 NHS Trusts in Wales. A range of measures were used. These included the General Health Questionnaire (GHQ-12), Maslach Burnout Inventory (MBI), Rosenberg Self-Esteem Scale (SES), Community Psychiatric Nursing (CPN) Stress Questionnaire, and PsychNurse Methods of Coping Questionnaire. The findings from the Rosenberg SES are reported here. Community mental health nurses in Wales scored as having average self-esteem. When the data were divided into high and low self-esteem, a large group of CMHNs (40%) were found to have low self-esteem. Factors that are associated with low and high self-esteem were identified. Alcohol consumption and being on lower nursing grades (D, E, F) were associated with low self-esteem, whilst amount of experience working as a CMHN was associated with high self-esteem.

Adaptation, Psychological↗
PubMed2000

Community mental health nurses in Wales: self-reported stressors and coping strategies.

There is evidence to suggest that community mental health nurses experience stress and burnout related to their work. Previous research has been limited by a number of methodological problems. One of the problems is that studies have tended to have small or unrepresentative samples, and many researchers have only examined mental health nurses as a subset within their research, which limits the generalizability of the findings. The All-Wales Community Mental Health Nurse (CMHN) Stress Study was set up in order to address this issue. The total population of CMHNs in Wales was surveyed (N = 614) and 301 (49%) responded. The questionnaire booklet contained a number of validated instruments to measure stress, burnout, and coping, together with a demographic questionnaire. The demographic questionnaire included three open ended-questions. These questions were asked in order in determine the CMHNs' own views of the sources of stress in the workplace, and to investigate which methods they use to cope. This paper reports the findings from the content analysis of the three questions. The results from the other measures are reported in the companion paper (Edwards et al. 2000). The most frequently cited stressors included perceived workload, excessive paperwork and administration, and a broad spectrum of client-related issues. Coping strategies that CMHNs reported using included peer support, a range of personal strategies such as relaxation, and belief in self and supervision. It appears from the findings that a range of factors such as organizational pressures and factors related to working with patients are important in determining stress levels, and that informal rather than formal support networks are the preferred methods of coping.

Adaptation, Psychological↗
PubMed2000

Stressors, moderators and stress outcomes: findings from the All-Wales Community Mental Health Nurse Study.

The All-Wales Community Mental Health Nurse Stress Study was the largest study undertaken in the UK to date to investigate stress, burnout and coping amongst the CMHN workforce. The aim of the study was to examine the variety, frequency and severity of stressors, to describe coping strategies used to reduce work-based stress, and to determine stress outcomes. Questionnaires were sent out to 614 CMHNs from ten NHS Trusts throughout Wales. The response rate was 49% (n = 301). The measures used included the Maslach Human Services Survey, the CPN Stress Questionnaire, the Psychnurse Methods of Coping Questionnaire, the Rosenberg Self-Esteem Scale and the General Health Questionnaire GHQ-12. Community mental health nurses indicated that trying to maintain a good quality service in the midst of long waiting lists, poor resources, and having too many interruptions while trying to work in the office were particularly stressful items. The coping strategies that CMHNs utilized the most were having a stable home life and looking forward to going home at the end of the day, having outside interests and hobbies and talking to people that they got on well with. Forty per cent of CMHNs tended to view themselves negatively, feeling that others did not hold much respect for them. The GHQ-12 measure indicated that 35% of CMHNs had crossed a threshold of psychiatric caseness. Measured against a normative sample of mental health workers, 51% of CMHNs were experiencing high levels of long-term emotional exhaustion. Twenty-four per cent were suffering from high levels of depersonalization burnout and were not relating well to clients, whilst 14% were experiencing severe long-term feelings of lack of personal accomplishment. The results from the study provided us with a picture of stress and coping in CMHNs in Wales. Addressing these factors may help to reduce levels of experienced stress and burnout.

Adult↗
PubMed2000

Identification of transposon-tagged genes by the random sequencing of Mutator-tagged DNA fragments from Zea mays.

We have used a universal adaptor amplification procedure to isolate random Mutator-tagged fragments from Mutator-active maize plants. Direct sequence characterization of 761 Mutator-tagged fragments indicated that a significant number were homologous to sequences within the public databases. The ability of Mutator-tagged fragments to detect homology was not related to the length of the sequence within the range 100-400 bp. However, fragments above this size did show an increased chance of detecting homology to either expressed sequence tags or genes. Characterization of the insertion sites of the Mutator elements suggested that while it does target transcribed regions, Mutator does not appear to have any site preference within the transcription unit. Hybridization of previously unidentified Mutator-tagged fragments to arrayed cDNA libraries confirmed that many of these also showed homology to transcribed regions of the genome. Examination of back-crossed progeny confirmed that all the insertions examined were germinal; however, in all but one case, selfing five individual Mutator-tagged lines failed to reveal an obvious phenotype. This study suggests that the random sequencing of Mutator-tagged fragments is capable of producing both a significant number of interesting transposon tagged genes and mutant plant lines, all of which could be extremely valuable in future gene discovery and functional genomics programmes.

Amino Acid Sequence↗
PubMed2000

Cancer registries--future development and uses in Britain.

Cancer registries are a vital source of information on cancer epidemiology and cancer services. Their role has changed dramatically over the past 15 years. A number of factors will affect their future role, including health service changes, information technology, development of clinical datasets and greater demand for both health service and public information. The potential of cancer registration needs to be realized by clinicians and health authorities: how they can use the data, its limitations, and how they can support and influence it through this period of change. A strategic direction is needed so that cancer registries develop into a dynamic, interactive source of knowledge for the twenty-first century.

Confidentiality↗
PubMed2000

A randomized controlled trial of exercise to improve outcomes of acute hospitalization in older adults.

OBJECTIVE: Older adults hospitalized for nondisabling diagnoses can lose functional ability. Lack of exercise or physical activity during the acute illness and recovery may be contributory. This study evaluated whether increased exercise in hospital and afterward would shorten length of stay and improve physical function at 1 month. DESIGN: A randomized controlled trial. SETTING: A 700-bed community-based hospital with academic and teaching programs. PARTICIPANTS: Three hundred patients (mean age 78.2 years +/- 5.6) with nondisabling medical and surgical diagnoses who were admitted to an acute care hospital between December 1990 and April 1992. All patients had an expected length of stay 5 or more days, were ambulatory before admission, and were not expected to die within 12 months. INTERVENTION: A hospital-based general exercise program was administered to intervention patients along with encouragement to continue the program, self-administered, at home. MEASUREMENTS: The primary outcome was hospital length of stay. Secondary outcomes at 1 month post-discharge included measures of physical function and other general health indicators. RESULTS: There was no significant difference in length of stay between treatment and control groups controlling for baseline characteristics and diagnoses. The intervention was associated with better function in instrumental activities of daily living (beta = .433 (95% CI, 0.044-0.842)) at 1 month but no change in perceived general health status and other measures of physical function. CONCLUSIONS: An exercise program started during hospitalization and continued for 1 month did not shorten length of stay but did improve functional outcome at 1 month.

Activities of Daily Living↗
PubMed2000

Structural characterization of the released polysaccharide of desiccation-tolerant Nostoc commune DRH-1.

The structure of the viscous extracellular polysaccharide (glycan) of desiccation-tolerant Nostoc commune DRH-1 was determined through chromatographic and spectroscopic methods. The polysaccharide is novel in that it possesses a 1-4-linked xylogalactoglucan backbone with D-ribofuranose and 3-O-[(R)-1-carboxyethyl]-D-glucuronic acid (nosturonic acid) pendant groups. The presence of D-ribose and nosturonic acid as peripheral groups is unusual, and their potential roles in modulating the rheological properties of the glycan are discussed. Nosturonic acid was present in the glycans of N. commune from diverse geographic locations, suggesting that this uronic acid is an integral component of this cosmopolitan anhydrophile.

Carbohydrate Conformation↗
PubMed2000

Hepatic abscesses as the primary presentation of Crohn's disease.

Hepatic Abscesses have been reported in association with Crohn's disease (CD). They either occur as a complication of known CD, or as in this case, are the presentation of undiagnosed disease. The management of the CD associated with liver abscesses is a matter of debate. We report a case of CD presenting with hepatic abscesses, review the literature and discuss the management options.

Crohn Disease↗
PubMed2000

Progesterone receptor isoform A but not B is expressed in endometriosis.

We previously demonstrated that 17beta hydroxysteroid dehydrogenase type 2, the enzyme that inactivates estradiol to estrone, is expressed in luteal eutopic endometrium in response to progesterone but not in simultaneously biopsied peritoneal endometriotic tissue. This molecular evidence of progesterone resistance, together with the clinical observation of resistance of endometriosis to treatment with progestins, led us to determine the levels of progesterone receptor (PR) isoforms PR-A and PR-B in eutopic endometrial and extra-ovarian endometriotic tissues. It was proposed that progesterone action on target genes is mediated primarily by homodimers of PR-B, whereas the truncated variant PR-A acts as a repressor of PR-B function. Immunoprecipitation, followed by Western blot analysis, was performed to detect bands specific for PR-A and PR-B in paired samples of endometriotic and eutopic endometrial tissues simultaneously biopsed from 18 women undergoing laparoscopy during various phases of the menstrual cycle. PR-B was present in 17 of 18 eutopic endometrial samples, and its level increased in the preovulatory phase, as expected, whereas PR-A was detected in all samples (n = 18) with a similar, but less prominent, cyclic variation in its levels. In endometriotic samples, however, no detectable PR-B could be demonstrated, whereas PR-A was detected in all samples (n = 18), albeit in much lower levels and without any cyclic variation in contrast with the eutopic endometrium. Levels of PR-A and PR-B in endometriotic and eutopic endometrial tissues were determined and compared after normalization to total protein and estrogen receptor-alpha levels. Using RNase protection assay, we also demonstrated indirectly that only PR-A transcripts were present in endometriotic tissue samples (n = 8), whereas both PR-A and PR-B transcripts were readily detectable in all eutopic endometrial samples (n = 8). This was indicative that failure to detect PR-B protein in endometriotic tissues is due to the absence of PR-B transcripts. We conclude that progesterone resistance in endometriotic tissue from laboratory and clinical observations may be accounted for by the presence of the inhibitory PR isoform PR-A and the absence of the stimulatory isoform PR-B.

Adult↗