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Biomedical subjects

J G Williams

Publications and source records attributed to J G Williams.

At least 37 records · Page 2Linked to original sources

Pragmatic randomised trial to evaluate the use of patient held records for the continuing care of patients with cancer.

OBJECTIVE: To evaluate the use of a multidisciplinary record held by patients with cancer in the community. DESIGN: Pragmatic randomised controlled trial. SETTING: The environs of Swansea in south west Wales. PARTICIPANTS: 501 patients under the care of the Department of Oncology, Singleton Hospital, Swansea. INTERVENTION: A patient held record used by the patient and healthcare professionals. Main outcome measures-Health related quality of life (EORTC QLQ-C30) measured at entry into the study and at 6 months; patients' views at 6 months; healthcare professionals' views collected after the completion of patient follow up; NHS resource and booklet use. RESULTS: 1148 patients were eligible for the study; 501 were recruited (44%) and 344 completed the study (172 in each group). There was no significant difference between the two groups in change in quality of life or NHS resource use. The patient held record did not have an impact on communication but was significantly helpful to patients in preparing for appointments, reducing difficulties in monitoring their own progress, and helping them to feel more in control (p<0.05). Fifty three percent of patients would have preferred not to have a patient held record. There was a low level of use of the record by healthcare professionals but most of those who remembered using it indicated that they would prefer patients to have it. CONCLUSIONS: The patient held record is valued by some patients and professionals but has no significant impact on the quality of life of patients or NHS resource use. It has a positive impact on quality by helping patients feel more in control and prepare for meetings with healthcare staff. Patients who find it useful tend to be younger and have more professionals involved in their care. It is recommended that it should be made available to patients on request and used by them according to need.

Adolescent↗

Glycogen synthase kinase-3 enhances nuclear export of a Dictyostelium STAT protein.

Extracellular cAMP stimulates the rapid tyrosine phosphorylation and nuclear translocation of the DICTYOSTELIUM: STAT protein Dd-STATa. Here we show that it also induces serine phosphorylation by GskA, a homologue of glycogen synthase kinase-3 (GSK-3). Tyrosine phosphorylation occurs within 10 s of stimulation, whereas serine phosphorylation takes 5 min, matching the kinetics observed for the cAMP regulation of GskA. Phosphorylation by GskA enhances nuclear export of Dd-STATa. The phosphorylated region, however, is not itself a nuclear export signal and we identify a region elsewhere in the protein that mediates nuclear export. These results suggest a biphasic regulation of Dd-STATa, in which extracellular cAMP initially directs nuclear import and then, via GskA, promotes its subsequent export. It also raises the possibility of an analogous regulation of STAT nuclear export in higher eukaryotes.

Active Transport, Cell Nucleus↗

An F-Box/WD40 repeat-containing protein important for Dictyostelium cell-type proportioning, slug behaviour, and culmination.

FbxA is a novel member of a family of proteins that contain an F-box and WD40 repeats and that target specific proteins for degradation via proteasomes. In fruiting bodies formed from cells where the fbxA gene is disrupted (fbxA(-) cells), the spore mass fails to fully ascend the stalk. In addition, fbxA(-) slugs continue to migrate under environmental conditions where the parental strain immediately forms fruiting bodies. Consistent with this latter behaviour, the development of fbxA(-) cells is hypersensitive to ammonia, the signaling molecule that regulates the transition from the slug stage to terminal differentiation. The slug comprises an anterior prestalk region and a posterior prespore region and the fbxA mRNA is highly enriched in the prestalk cells. The prestalk zone of the slug is further subdivided into an anterior pstA region and a posterior pstO region. In fbxA(-) slugs the pstO region is reduced in size and the prespore region is proportionately expanded. Our results indicate that FbxA is part of a regulatory pathway that controls cell fate decisions and spatial patterning via regulated protein degradation.

Amino Acid Motifs↗

Elucidation of binding determinants and functional consequences of Ras/Raf-cysteine-rich domain interactions.

Raf-1 is a critical downstream target of Ras and contains two distinct domains that bind Ras. The first Ras-binding site (RBS1) in Raf-1 has been shown to be essential for Ras-mediated translocation of Raf-1 to the plasma membrane, whereas the second site, in the Raf-1 cysteine-rich domain (Raf-CRD), has been implicated in regulating Raf kinase activity. While recognition elements that promote Ras.RBS1 complex formation have been characterized, relatively little is known about Ras/Raf-CRD interactions. In this study, we have characterized interactions important for Ras binding to the Raf-CRD. Reconciling conflicting reports, we found that these interactions are essentially independent of the guanine nucleotide bound state, but instead, are enhanced by post-translational modification of Ras. Specifically, our findings indicate that Ras farnesylation is sufficient for stable association of Ras with the Raf-CRD. Furthermore, we have also identified a Raf-CRD variant that is impaired specifically in its interactions with Ras. NMR data also suggests that residues proximal to this mutation site on the Raf-CRD form contacts with Ras. This Raf-CRD mutant impairs the ability of Ras to activate Raf kinase, thereby providing additional support that Ras interactions with the Raf-CRD are important for Ras-mediated activation of Raf-1.

Animals↗

The UK IBDQ-a British version of the inflammatory bowel disease questionnaire. development and validation.

Measurement of health-related quality of life (HRQL) is becoming more important in studies of patients with inflammatory bowel disease. The McMaster IBDQ is the most widely used HRQL instrument for these patients. However, its use with patients in the United Kingdom has not been validated. This study develops and validates a UK version of the McMaster IBDQ (UK IBDQ). The UK IBDQ was tested with two samples of patients for its reliability, validity, reproducibility, and responsiveness. The first sample consisted of 180 patients participating in a randomized clinical trial. The second was recruited from members of the National Association for Colitis and Crohns Disease. Reliability of the subscales and the summary score of the UK IBDQ is demonstrated by Cronbach's alpha and item-total correlations. Their validity is demonstrated by their correlations with SF-36 subscales and an empirical index of disease activity. Good intraclass correlations and responsiveness ratios show their reproducibility and responsiveness. The findings support the reliability, validity, reproducibility, and responsiveness of the UK IBDQ and its acceptability to patients in UK.

Emotions↗

Open access follow up for inflammatory bowel disease: pragmatic randomised trial and cost effectiveness study.

OBJECTIVE: To evaluate whether follow up of patients with inflammatory bowel disease is better through open access than by routine booked appointments. DESIGN: Pragmatic randomised controlled trial. SETTING: Two district general hospitals in Swansea and Neath, Wales. PARTICIPANTS: 180 adults (78 with Crohn's disease, 77 ulcerative or indeterminate colitis, 25 ulcerative or idiopathic proctitis) recruited from outpatient clinics during October 1995 to November 1996. INTERVENTION: Open access follow up according to patient need. MAIN OUTCOME MEASURES: Generic (SF-36) and disease specific (UK inflammatory bowel disease questionnaire UKIBDQ) quality of life, number of primary and secondary care contacts, total resource use, and views of patients and general practitioners. RESULTS: There were no differences in generic or disease specific quality of life. Open access patients had fewer day visits (0.21 v 0. 42, P<0.05) and fewer outpatient visits ( 4.12 v 4.64, P<0.01), but some patients had difficulty obtaining an urgent appointment. There were no significant differences in specific investigations undertaken, inpatient days, general practitioner surgery or home visits, drugs prescribed, or total patient borne costs. Mean total cost in secondary care was lower for open access patients (P<0.05), but when primary care and patient borne costs were added there were no significant differences in total costs to the NHS or to society. General practitioners and patients preferred open access. CONCLUSIONS: Open access follow up delivers the same quality of care as routine outpatient care and is preferred by patients and general practitioners. It uses fewer resources in secondary care but total resource use is similar. Better methods of ensuring urgent access to outpatient clinics are needed.

Adult↗

STAT signalling in cell proliferation and in development.

Recent advances in STAT signalling research include a better understanding of the roles of mammalian STAT proteins in cell proliferation and apoptosis, and of non-mammalian STAT proteins in morphogenesis. Two different ways in which STAT signalling pathways can interface with Smad signalling pathways significantly increasing combinatorial signalling possibilities, have also been described.

Animals↗

HAPPY days for the Dictyostelium genome project.

Without the HAPPY map, the collaborators in the genome project would have found assembly to be extremely difficult, and the Dictyostelium genome sequence would perhaps have been left highly incomplete. With the HAPPY Map the YAC clones can be remapped and the original YAC skim strategy followed. In conclusion, this method has already made one community very happy and seems sure to make its mark in many other genome projects.

Animals↗

Analysis of the promoter of the cudA gene reveals novel mechanisms of Dictyostelium cell type differentiation.

The cudA gene encodes a nuclear protein that is essential for normal multicellular development. At the slug stage cudA is expressed in the prespore cells and in a sub-region of the prestalk zone. We show that cap site distal promoter sequences direct cudA expression in prespore cells, while proximal sequences direct expression in the prestalk sub-region. The promoter domain that directs prespore-specific transcription consists of a positively acting region, that has the potential to direct expression in all cells within the slug, and a negatively acting region that prevents expression in the prestalk cells. Dd-STATa is the STAT protein that regulates commitment to stalk cell gene expression, where it is known to function as a transcriptional repressor. We show that Dd-STATa binds in vitro to the positively acting part of the prespore domain of the cudA promoter. However, Dd-STATa cannot be utilised for this purpose in vivo, because analysis of a Dd-STATa null mutant strain shows that Dd-STATa is not necessary for cudA transcription in prespore cells. In contrast, the part of the cudA promoter that directs prestalk-specific expression contains a binding site for Dd-STATa that is essential for its biological activity. Dd-STATa appears therefore to serve as a direct activator of cudA transcription in prestalk cells, while a protein with a DNA binding specificity highly related to that of Dd-STATa is utilised to activate cudA transcription in prespore cells.

Actins↗

Effect of steroids on posttonsillectomy pain in adults.

OBJECTIVE: To determine whether a single intraoperative dose of intravenous dexamethasone has an effect on pain after tonsillectomy. DESIGN: Double-blinded randomized controlled clinical trial. SUBJECTS: Thirty-four consecutive nonpediatric patients presenting for tonsillectomy. INTERVENTION: Patients scheduled for electrocautery tonsillectomy were randomized to receive either intravenous dexamethasone or placebo during surgery. Pain was measured twice daily for 10 days by means of a visual analog scale. RESULTS: There were no statistically significant differences between the groups, but the dexamethasone group had a trend to report less pain over the first several days. The dexamethasone group received less analgesic in the recovery room, but there were no differences between the groups in the 10 days afterward. CONCLUSIONS: There is evidence that a single dose of dexamethasone reduces pain after tonsillectomy to a small degree. A single dose was not associated with adverse effects, so the risk-benefit ratio may be favorable for this practice.

Adolescent↗

Introduction.

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Animals↗

Admission level of Gc-globulin predicts outcome after multiple trauma.

BACKGROUND: Actin is the dominating protein in mammalian cells. Release of excessive amounts of actin into the circulation may result in a condition resembling multiple organ failure. The purpose of this study was to determine if admission levels of Gc-globulin can predict survival after multiple trauma. Also, we wanted to compare the predictive ability of Gc-globulin with that of the TRISS-Like scoring system. METHODS: Fifty-seven patients with a median ISS 18 (16-75) were included. All patients had a blood sample taken median 42 min after the injury (19-110 min). Serum Gc-globulin was measured by rocket immunoelectrophoresis. RESULTS: On admission, all patients had significantly reduced levels of Gc-globulin compared with normal controls. Gc-globulin was significantly higher in the group of survivors (n = 41), compared with non-survivors (n = 16). Median 237 mg/l vs. 188 mg/l (P < 0.01). The predictive ability of Gc-globulin regarding death was similar to that of TRISS-Like with positive predictive values of 69%, a negative predictive value of 84%, a sensitivity of 56% and a specificity of 90%. CONCLUSIONS: The predictive value of Gc-globulin regarding survival was similar to that of an established scoring system. Gc-globulin, alone or in combination with other parameters, may serve as a routine tool for early identification of patients at risk after severe injury, increasing the possibility of early intervention.

Adolescent↗

The Dictyostelium genome project: an invitation to species hopping.

Dictyostelium allows some of the general problems of eukaryotic biology to be addressed by using molecular genetic tools that are more normally associated with yeast. The genome project, now underway, marks an important increase in the attractiveness of Dictyostelium as an experimental organism and will invite increased 'species hopping' by experimenters. We provide a brief guide to the problems that are being addressed in Dictyostelium, to the genome project itself and to the molecular genetic tools available for its exploitation.

Animals↗

The use of clinical information to help develop new services in a district general hospital.

This paper describes a case study of the use of clinical information to improve gastroenterological services in a district general hospital. The clinical information has been derived from aggregation and analysis of operational clinical data collected in coded, structured form on a clinical information system over a period of 8 years. The monitoring of activity, referral patterns and administrative and clinical outcomes, and the use of this information to develop new services to improve access to patients are described. It is concluded that the secondary use of clinical information derived from electronically captured data can have a significant impact on the development of services by a provider organisation, and on professional teamworking.

Algorithms↗