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Biomedical subjects

W G Scott

Publications and source records attributed to W G Scott.

At least 19 recordsLinked to original sources
PubMed1995

Hysterectomy for nonmalignant conditions: cost to New Zealand society.

AIMS: The aim of the study was to estimate the annual hospital costs to New Zealand society of hysterectomy for nonmalignant conditions in women between puberty and menopause, and to compare international rates for all hysterectomies. METHODS: The records of patients aged between 15 and 54 years inclusive, who had a hysterectomy for a nonmalignant menstrual condition, were researched. Hospital costs were estimated using specific hospital unit costs and prices. RESULTS: The 4390 hysterectomies for nonmalignant conditions represent 69% of the total hysterectomies undertaken in New Zealand in 1991. Estimated costs for all hospitals were $17 million or $3868 per hysterectomy. The all ages all conditions hysterectomy rate per 100,000 women of 365 (368 in 1992) in New Zealand is higher than in some other developed countries. CONCLUSIONS: Further reduction in the rate of hysterectomy in New Zealand may save hospital costs but these savings should be offset against the costs of any other treatment options chosen. Although it was found that unit costs of public hospitals were higher than those of private hospitals the case mix for the two types of hospital may differ and public hospital cost reductions may not be possible. Economic evaluation of alternative treatment options would be improved if all relevant costs (direct, indirect and intangible) were known. Further research is needed to determine the reasons why New Zealand women elect to have hysterectomies, why most choose a private hospital, and changes (before and after hysterectomy) in productivity, out of pocket expenses, and quality of life for these patients.

Adolescent↗
PubMed1995

Rapid crystallization of chemically synthesized hammerhead RNAs using a double screening procedure.

To find conditions for obtaining diffraction-quality crystals of a hammerhead RNA rapidly and reproducibly, we employed a "double screening" procedure in which we screened six different RNA synthetic constructs against 48 crystallization conditions using a newly devised sparse matrix. We obtained crystals immediately and diffraction-quality crystals of the sixth RNA construct within six months of initiating the screening of additional RNA sequences. The best crystals diffract to 2.9 A resolution when flash-cooled at synchrotron X-ray sources. Solid-support chemical synthesis combined with sparse matrix screening should allow rapid production of diffraction-quality crystals of a variety of small RNAs, reducing the time commitment for initiating such crystallography projects from several years to several months. The synthetic approach also makes introduction of modified bases to prevent self-cleavage and to generate isomorphous heavy-atom derivative crystals a rapid and straightforward process.

Base Sequence↗
PubMed1995

The crystal structure of an all-RNA hammerhead ribozyme: a proposed mechanism for RNA catalytic cleavage.

We have solved the crystal structure of an all-RNA hammerhead ribozyme having a single 2'-O-methyl cytosine incorporated at the active site to prevent cleavage. The conditions used differ from those in another recent solution in four significant ways: first, it is an all-RNA ribozyme rather than a DNA-RNA hybrid; second, the connectivity of the ribozyme backbone strands is different; third, the crystals were grown in the presence of a much lower concentration of salt; and fourth, the crystal packing scheme is very different. Nevertheless, the three-dimensional structure of the all-RNA hammerhead ribozyme is similar to the previous structure. Five potential Mg(II)-binding sites are identified, including one positioned near the ribozyme catalytic pocket. Upon this basis, as well as upon comparisons with the metal-binding sites in the structurally homologous uridine turn of tRNAPhe, we propose a mechanism for RNA catalytic cleavage.

Base Sequence↗
PubMed1995

Mutagenesis and Laue structures of enzyme intermediates: isocitrate dehydrogenase.

Site-directed mutagenesis and Laue diffraction data to 2.5 A resolution were used to solve the structures of two sequential intermediates formed during the catalytic actions of isocitrate dehydrogenase. Both intermediates are distinct from the enzyme-substrate and enzyme-product complexes. Mutation of key catalytic residues changed the rate determining steps so that protein and substrate intermediates within the overall reaction pathway could be visualized.

Binding Sites↗
PubMed1995

Pharmacoeconomic evaluation of roxithromycin versus amoxycillin/clavulanic acid in a community-acquired lower respiratory tract infection study.

A cost-effectiveness study of roxithromycin versus amoxycillin/clavulanic acid using data from a 242 patient multicentre trial in Australia and New Zealand was undertaken in the general practice treatment of infections of the lower respiratory tract (LRTI). Those patients assigned to roxithromycin required on average 1 day less of treatment, significantly fewer extended courses of treatment, and fewer patients experienced side effects considered to be related to the treatment. The cost benefit (difference between the two treatment costs) per clinical success was A$17.04*. By substituting roxithromycin for amoxycillin/clavulanic acid, Australia would save A$ 1.704 million per 100,000 episodes of LRTI. The results demonstrate that savings in direct costs can be achieved by substituting roxithromycin for amoxycillin/clavulanic acid in the treatment of community-acquired LRTI.

Adolescent↗
PubMed1994

Ischaemic stroke in New Zealand: an economic study.

AIM: To quantify and describe the annual cost of ischaemic stroke to New Zealand society during 1992. METHODS: A prevalence or cross sectional approach employing incremental estimation was used to estimate costs from the perspective of society. The study used unit record hospital and mortality data. RESULTS: Direct costs ranged from $93 million to $140 m and loss of production was between $6 m and $14 m. Total quantified costs were estimated to lie between $99 m and $154 m. Hospital and continuing care costs when combined make up 90% of all quantified costs. CONCLUSION: Ischaemic stroke affects mainly older people many of whom are discharged into the community and require costly community support or continuing care. The combination of an ageing population, increasing survival rates and constant incidence rates will result in a substantial rise in the costs of continuing care and community support. Most of these costs are at present obscured because much of the care provided does not involve money payments and/or data are not recorded and collated on a national basis. Incorrect policy decisions will be made if the nonhospital costs of stroke are not taken into account.

Adolescent↗
PubMed1994

Transmembrane signalling and the aspartate receptor.

BACKGROUND: The aspartate receptor is a transmembrane protein that mediates bacterial chemotaxis. The structures of the periplasmic ligand-binding domain reveal a dimer, each subunit with four alpha-helix bundles, with aspartate binding to one of two sites at the subunit interface. The transmembrane regions of the receptor were not included in these structures. RESULTS: To investigate the structure of the transmembrane region, we have made a mutant protein with two cross-links, restraining the subunit-subunit interface on both sides of the membrane, and have made an energy-minimized model of the transmembrane region. We demonstrate that the transmembrane helices form a coiled coil which extends from the periplasmic subunit through the membrane. We have constructed a model of the ligand-binding domains with the amino-terminal transmembrane helices. CONCLUSIONS: We draw three conclusions from our model. Firstly, the interface between receptor subunits in the intact receptor consists of an uninterrupted coiled coil. Secondly, this structure rules out several postulated mechanisms of signalling. Thirdly, side chain packing constraints within the helices dictate that local structural changes must be small, but are propagated over a long distance rather than being dissipated locally. Low energy changes in the conformation of side chains are a probable mechanism of signal transduction in the aspartate receptor.

Amino Acid Sequence↗
PubMed1993

Cost of coronary heart disease in New Zealand.

AIM: To conservatively estimate the costs of coronary heart disease from the perspective of New Zealand society. METHODS: A cross sectional or prevalence analysis (cases and associated costs in one year) was undertaken of the total annual cost of coronary heart disease. Estimates were made on an incremental basis of direct, indirect and intangible costs. Costs relate to 1989 volumes measured in March quarter 1992 dollars (net of goods and services tax). RESULTS: Cost estimates were in all instances conservative values. Direct medical costs amounted to $179 million and indirect costs were between $14 million and $24 million. Loss of life using the human capital approach ranged from $114 million to $264 million, but using the willingness to pay criteria, loss of life was $14,568 million. CONCLUSION: Because of the magnitude of the costs of coronary heart disease even small reductions in the incidence of coronary heart disease will produce substantial savings to society.

Absenteeism↗
PubMed1993

Refined structures of the ligand-binding domain of the aspartate receptor from Salmonella typhimurium.

The aspartate receptor is a transmembrane-signalling protein that mediates chemotaxis behaviour in bacteria. Aspartate receptors in Salmonella typhimurium and Escherichia coli exist as dimers of two subunits in the presence as well as in the absence of aspartate. We have previously reported the three-dimensional structures of the external ligand-binding domain of the S. typhimurium aspartate receptor with and without bound aspartate. The external or periplasmic region of the aspartate receptor is a dimer of four-alpha-helical bundle subunits; a single aspartate molecule binds to one of two sites residing at the subunit interface, increasing the affinity of the subunits for one another. Here we report the results of a detailed analysis of the aspartate receptor ligand-binding domain structure (residues 25 to 188). The dimer interface between the twofold related subunits consists primarily of contacts mediated by the side-chains of the N-terminal helix of each four-alpha-helical bundle subunit. The N-terminal helices pack approximately 20 degrees from parallel as an approximate coiled-coil super-secondary structure. We have refined aspartate receptor ligand-binding domain structures in the presence and in the absence of a bound aromatic compound, 1,10-phenanthroline, to 2.2 A and 2.3 A resolution, respectively, as well as crystal structures in the presence of specifically bound Au(I), Hg(II) and Pt(IV) complex ions at 2.4 A, 3.0 A and 3.3 A resolution, respectively. The possible biological relevance of the aromatic ligand-binding site and the metal ion-binding sites is discussed. The dimer of four-alpha-helical bundle subunits composing the periplasmic region of the S. typhimurium aspartate receptor provides a basis for understanding the results of mutational analyses performed on related chemotaxis transmembrane receptors. The crystal structure analysis provides an explanation for the way in which mutations in the E. coli aspartate receptor affect its binding to the periplasmic maltose-binding protein and how mutations in the more distantly related E. coli Trg chemotaxis receptor affect its binding to the periplasmic ribose and glucose-galactose binding proteins.

Aspartic Acid↗
PubMed1991

Three-dimensional structures of the ligand-binding domain of the bacterial aspartate receptor with and without a ligand.

The three-dimensional structure of an active, disulfide cross-linked dimer of the ligand-binding domain of the Salmonella typhimurium aspartate receptor and that of an aspartate complex have been determined by x-ray crystallographic methods at 2.4 and 2.0 angstrom (A) resolution, respectively. A single subunit is a four-alpha-helix bundle with two long amino-terminal and carboxyl-terminal helices and two shorter helices that form a cylinder 20 A in diameter and more than 70 A long. The two subunits in the disulfide-bonded dimer are related by a crystallographic twofold axis in the apo structure, but by a noncrystallographic twofold axis in the aspartate complex structure. The latter structure reveals that the ligand binding site is located more than 60 A from the presumed membrane surface and is at the interface of the two subunits. Aspartate binds between two alpha helices from one subunit and one alpha helix from the other in a highly charged pocket formed by three arginines. The comparison of the apo and aspartate complex structures shows only small structural changes in the individual subunits, except for one loop region that is disordered, but the subunits appear to change orientation relative to each other. The structures of the two forms of this protein provide a step toward understanding the mechanisms of transmembrane signaling.

Amino Acid Sequence↗
PubMed1991

Crystallization and preliminary X-ray diffraction study of the ligand-binding domain of the bacterial chemotaxis-mediating aspartate receptor of Salmonella typhimurium.

The periplasmic domain of the aspartate chemotaxis receptor from Salmonella typhimurium has been crystallized in the presence and absence of bound aspartate. Both crystal forms were grown by precipitation with lithium sulfate and diffract to 1.8 A resolution. The aspartate receptor structure is believed to be prototypical of a large class of receptors including those for polypeptide growth factor hormones as well as those for small chemotaxis-affector molecules such as aspartate and serine.

Aspartic Acid↗