Search PubMed⌕ Search

Biomedical subjects

J Raftery

Publications and source records attributed to J Raftery.

At least 37 records · Page 2Linked to original sources

Structure of lobster apocrustacyanin A1 using softer X-rays.

The molecular basis of the camouflage colouration of marine crustacea is often provided by carotenoproteins. The blue colour of the lobster carapace, for example, is intricately associated with a multimacromolecular 16-mer complex of protein subunits each with a bound astaxanthin molecule. The protein subunits of crustacyanin fall into two distinct subfamilies, CRTC and CRTA. Here, the crystal structure solution of the A(1) protein of the CRTC subfamily is reported. The problematic nature of the structure solution of the CRTC proteins (both C(1) and A(1)) warranted consideration and the development of new approaches. Three putative disulfides per protein subunit were likely to exist based on molecular-homology modelling against known lipocalin protein structures. With two such subunits per crystallographic asymmetric unit, this direct approach was still difficult as it involved detecting a weak signal from these sulfurs and suggested the use of softer X-rays, combined with high data multiplicity, as reported previously [Chayen et al. (2000), Acta Cryst. D56, 1064-1066]. This paper now describes the structure solution of CRTC in the form of the A(1) dimer based on use of softer X-rays (2 A wavelength). The structure solution involved a xenon derivative with an optimized xenon L(I) edge f" signal and a native data set. The hand of the xenon SIROAS phases was determined by using the sulfur anomalous signal from a high-multiplicity native data set also recorded at 2 A wavelength. For refinement, a high-resolution data set was measured at short wavelength. All four data sets were collected at 100 K. The refined structure to 1.4 A resolution based on 60 276 reflections has an R factor of 17.7% and an R(free) of 22.9% (3137 reflections). The structure is that of a typical lipocalin, being closely related to insecticyanin, to bilin-binding protein and to retinol-binding protein. This A(1) monomer or dimer can now be used as a search motif in the structural studies of the oligomeric forms alpha- and beta-crustacyanins, which contain bound astaxanthin molecules.

Amino Acid Sequence↗

The 1.2 A resolution structure of the Con A-dimannose complex.

The complex between concanavalin A (Con A) and alpha1-2 mannobiose (mannose alpha1-2 mannose) has been refined to 1.2 A resolution. This is the highest resolution structure reported for any sugar-lectin complex. As the native structure of Con A to 0.94 A resolution is already in the database, this gives us a unique opportunity to examine sugar-protein binding at high resolution. These data have allowed us to model a number of hydrogen atoms involved in the binding of the sugar to Con A, using the difference density map to place the hydrogen atoms. This map reveals the presence of the protonated form of Asp208 involved in binding. Asp208 is not protonated in the 0.94 A native structure. Our results clearly show that this residue is protonated and hydrogen bonds to the sugar. The structure accounts for the higher affinity of the alpha1-2 linked sugar when compared to other disaccharides. This structure identifies different interactions to those predicted by previous modelling studies. We believe that the additional data presented here will enable significant improvements to be made to the sugar-protein modelling algorithms.

Concanavalin A↗

Stroke rehabilitation after hospital discharge: a randomized trial comparing domiciliary and day-hospital care.

OBJECTIVES: To compare the effectiveness and costs of a new domiciliary rehabilitation service for elderly stroke patients with geriatric day-hospital care. DESIGN: Randomized controlled trial. PARTICIPANTS: Stroke patients aged 55+ who required further rehabilitation after hospital discharge or after referral to geriatricians from the community. SETTING: Poole area, East Dorset, a mixed urban/rural area on the south coast of England. MAIN OUTCOMES: Primary-changes between hospital discharge and 6-month follow-up in physical function as measured by Barthel index. Secondary-changes over this period in Rivermead Mobility Index and mental state (Philadelphia Geriatric Centre Morale Scale) and differences in social activity (Frenchay Activities Index) and generic health status (SF-36). Health service and social service cost per patient were compared for the two groups. RESULTS: 180 patients were eligible and 140 (78%) were randomized. The groups were well balanced for age, sex, social class and initial Barthel index. We achieved follow-up in 88% of subjects who were alive at 6 months. We detected no significant differences in patient outcomes, although there was a non-significant improvement in measures of physical function and social activity in the domiciliary group. Domiciliary patients had more physiotherapy time per session and more district nurse time, and made greater use of social service day centres and home helps. Total cost per patient did not differ significantly between the two groups, with reduced health service costs in the domiciliary arm offset by higher social service costs. CONCLUSION: No significant differences were detected in the effectiveness of the two services. Neither service influenced patients' mental state, and their social activity remained low. Total costs were similar. A mixed model of day-hospital and domiciliary care may be most cost-effective for community stroke rehabilitation, but this requires further evaluation.

Aged↗

Hampshire depression project: changes in the process of care and cost consequences.

Records of patients included in a trial of educating practice teams about the management of depression were examined to determine changes in the process of care. There were no significant differences in the proportions recognised or treated for depression. Only 15% of those with possible, and 26% of those with probable, major depressive disorder were prescribed recommended doses and duration of antidepressants. The education apparently delayed a switch away from tricyclics while achieving a similar outcome. However health service costs were mainly non-psychiatric, and there were no significant savings as a result.

Antidepressive Agents↗

Anticoagulation management in primary care: a trial-based economic evaluation.

The demand for anticoagulation management is increasing because of a widening of the indications of treatment. A primary care clinic using near-patient testing and computer decision support software is one model of care to meet this increased demand. The study aimed to determine the cost and cost-effectiveness of primary care-based anticoagulation management in comparison with 'traditional' hospital care-based provision by means of a cost-effectiveness analysis using data from a Birmingham-based multicentre randomized controlled trial. The costs per patient per year in primary care were pound170 [95% confidence interval (CI) pound149-190] vs. pound69 (95% CI pound57-81). Sensitivity analysis demonstrated that the cost in primary care could be reduced to under pound100 per patient per year under plausible changes in the variables. Primary care provides similar levels of control to secondary care for patients on anticoagulation therapy. There is an increased cost of managing patients in primary care and at no point did primary care become a lower cost option than secondary care. Local decision-makers need to assess the increased cost of primary care anticoagulation management in terms of the potential reductions in high-cost serious adverse events.

Aged↗

Direct determination of the positions of the deuterium atoms of the bound water in -concanavalin A by neutron Laue crystallography.

The correct positions of the deuterium (D) atoms of many of the bound waters in the protein concanavalin A are revealed by neutron Laue diffraction. The approach includes cases where these water D atoms show enough mobility to render them invisible even to ultra-high resolution synchrotron-radiation X-ray crystallography. The positions of the bound water H atoms calculated on the basis of chemical and energetic considerations are often incorrect. The D-atom positions for the water molecules in the Mn-, Ca- and sugar-binding sites of concanavalin A are described in detail.

Binding Sites↗

Apocrustacyanin A1 from the lobster carotenoprotein alpha-crustacyanin: crystallization and initial X-ray analysis involving softer X-rays.

The A1 subunit of the carotenoprotein alpha-crustacyanin, isolated from lobster carapace, has been crystallized using the vapour-diffusion method. The crystals, grown in solutions of ammonium sulfate containing methylpentanediol (MPD), diffracted to 2. 0 A. The crystals are stable to radiation. The space group of the crystals is P2(1)2(1)2(1). The unit-cell parameters are a = 41.9, b = 80.7, c = 110.8 A. 'Standard structure determination' has been unsuccessful within this crustacyanin family. Instead, an approach based on the S atoms is being undertaken involving softer X-rays at the SRS, Daresbury.

Animals↗

Purification, crystallization and initial X-ray analysis of the C1 subunit of the astaxanthin protein, V600, of the chondrophore Velella velella.

The subunit C1 of the carotenoid-binding protein, V600, of the chondrophore Velella velella has been purified and crystallized. The crystals, which were grown by the vapour-diffusion method from ammonium sulfate as the major precipitant, diffract beyond 3 A and show little radiation damage over long periods (greater than 100 h) on a Cu Kalpha rotating-anode X-ray source. The space group of the crystals is P212121 with cell dimensions a = 42.0, b = 80.9, c = 110. 6 A.

Animals↗

Methodological limitations of cost-effectiveness analysis in health care: implications for decision making and service provision.

This article reviews the methodological limitations identified in a recent authoritative US report by the Public Health Service, which provides the theoretical background to several other guidelines on cost effectiveness, such as those of the British Medical Journal. It places each limitation in context and discusses the implications of each individually and collectively. It concludes that while the report's interim solution by consensus agreement offers a way forward in the short term, the complexities identified reveal a range of limitations to the more heroic uses of cost effectiveness analysis in healthcare. More modest approaches, it is suggested, may have greater practical relevance.

Cost-Benefit Analysis↗