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Biomedical subjects

I Shaw

Publications and source records attributed to I Shaw.

At least 19 recordsLinked to original sources

Protection from IBDV-induced bursal damage by a recombinant fowlpox vaccine, fpIBD1, is dependent on the titre of challenge virus and chicken genotype.

Expression of the VP2 capsid protein of infectious bursal disease virus (IBDV) in an vaccine strain of fowlpox has produced an experimental recombinant vaccine, fpIBD1. Successful vaccination with fpIBD1 was dependent on the titre of challenge virus for high titres of challenge virus were able to overcome protection induced by fpIBD1 whereas challenge with a low titre of virus did not. The genotype of chicken also has an important effect on the outcome of challenge possibly as a result of the major histocompatability complex and its ability to present VP2-derived peptides to the immune system. It was not possible to protect the inbred white leghorn chicken strain, line 15I, from IBDV-induced bursal damage by vaccination with fpIBD1 even at the lowest titre of challenge virus used. All other inbred white leghorn chickens examined (line 6(1), C. B4 and C.B12) and outbred Rhode Island Red chickens were protected by fpIBD1. Protection by the fpIBD1 vaccine is induced in the absence of detectable serum antibodies, suggesting the possibility of a significant role for cell-mediated immunity in protection from IBDV challenge.

Animals↗

Gene organisation determines evolution of function in the chicken MHC.

Some years ago, we used our data for class I genes, proteins and peptide-binding specificities to develop the hypothesis that the chicken B-F/B-L region represents a "minimal essential MHC". In this view, the B locus contains the classical (highly expressed and polymorphic) class I alpha and class II beta multigene families, which are reduced to one or two members, with many other genes moved away or deleted from the chicken genome altogether. We found that a single dominantly expressed class I gene determines the immune response to certain infectious pathogens, due to peptide-binding specificity and cell-surface expression level. This stands in stark contrast to well-studied mammals like humans and mice, in which every haplotype is more-or-less responsive to every pathogen and vaccine, presumably due to the multigene family of MHC molecules present. In order to approach the basis for a single dominantly expressed class I molecule, we have sequenced a portion of the B complex and examined the location and polymorphism of the class I (B-F) alpha, TAP and class II (B-L) beta genes. The region is remarkably compact and simple, with many of the genes expected from the MHC of mammals absent, including LMP, class II alpha and DO genes as well as most class III region genes. However, unexpected genes were present, including tapasin and putative natural killer receptor genes. The region is also organised differently from mammals, with the TAPs in between the class I genes, the tapasin gene in between the class II (B-L) beta genes, and the C4 gene outside of the class I alpha and class II beta genes. The close proximity of TAP and class I alpha genes leads to the possibility of co-evolution, which can drive the use of a single dominantly expressed class I molecule with peptide-binding specificity like the TAP molecule. There is also a single dominantly expressed class II beta gene, but the reason for this is not yet clear. Finally, the presence of the C4 gene outside of the classical class I alpha and class II beta genes suggests the possibility that this organisation was ancestral, although a number of models of organisation and evolution are still possible, given the presence of the Rfp-Y region with non-classical class I alpha and class II beta genes as well as the presence of multigene families of B-G and rRNA genes.

Animals↗

Driving drug discovery and patient therapy via the encapsulation and fusion of knowledge.

Knowledge and Knowledge Management are becoming common senior management parlance in the Pharmaceutical Industry in the late 1990s. This perspective article will address exactly what is knowledge and the various techniques available to harness and use it to drive the pharmaceutical business process. The impact of knowledge on this process to provide a better service to the industry's customers (the patient) are discussed with respect to the key business problems facing the industry as it enters the new millennium.

Artificial Intelligence↗

Assessing quality in health care services: lessons from mental health nursing.

Quality in health care services is neither a simple nor an apolitical issue. Quality is a complex concept and how it is defined and measured has important consequences for services. The definition and measurement of service quality in health care has slipped from professional toward managerial control. Professionals such as nurses have an absolute concept of quality which is a part of their value system and based upon their training and experience. Managerial concepts of quality may be influenced by other organizational concerns such as the pursuit of efficiency. This paper outlines quality assurance systems in mental health nursing and the wider quality debate and argues that there may well be a trade-off between quality of service and efficiency. The moves toward outcome measures and performance indicators are also discussed and the argument forwarded that such a focus serves to exclude users and cloaks serious issues in service delivery. The argument of this paper is that evaluation of service quality needs to include users, and this could provide them with a platform for enhanced involvement in service planning.

Community Mental Health Services↗

Assessing quality in mental health care. The United Kingdom experience.

Quality assessment in mental health services is undergoing change in the United Kingdom following the introduction of market reforms. Traditionally, service quality was monitored by professional practitioners with reference to user satisfaction. This became formalized, and the two main forms of quality assurance currently used are outlined. However, the government is concerned that this may be inadequate for the monitoring of quality standards, specified in contracts between service purchasers and providers, and that existing systems provide an insufficient indication of service outcome. As a consequence, the government financed the development of a new set of health outcome scales. The importance of these scales are discussed.

Community Participation↗

Fibrinogen levels correlate with stage of disease in patients with oesophageal cancer.

BACKGROUND: A hypercoagulable state is well recognized in association with cancer and results in a greatly increased risk of thromboembolic disease during surgery in these patients. This study examines routine laboratory measurements of coagulation and attempts to correlate these with disease stage in patients with oesophageal cancer. METHODS: Fibrinogen concentration, platelet count and routine coagulation tests were examined before operation in a consecutive group of 73 patients with oesophageal carcinoma. All patients were staged according to standard Union Internacional Contra la Cancrum criteria. RESULTS: The fibrinogen concentration was significantly higher in patients with oesophageal carcinoma than in age- and sex-matched control patients with benign disease (P < 0.005). Fibrinogen concentration was higher in patients with greater depth of invasion (P < 0.005) and those with metastatic disease (P < 0.01). CONCLUSION: This study demonstrates a stage-dependent phenomenon of hyperfibrinogenaemia in association with oesophageal carcinoma.

Aged↗

Inhibition of plasminogen activator inhibitor-1 activity by two diketopiperazines, XR330 and XR334 produced by Streptomyces sp.

Two diketopiperazines, XR334 (1) and the novel compound XR330 (2), were isolated from the lyophilised biomass of an unidentified Streptomyces sp. Their structures were elucidated on the basis of spectroscopic studies and confirmed by chemical synthesis. Both compounds inhibited plasminogen activator inhibitor-1 activity in an amidolytic assay of tissue plasminogen activator mediated plasmin generation. Compound 1 also enhanced fibrinolysis ex vivo and protected against thrombus formation in the rat. These diketopiperazines represent the first low molecular weight inhibitors of plasminogen activator inhibitor-1, a physiological regulator of fibrinolysis.

Animals↗

Identifying small-molecule lead compounds: the screening approach to drug discovery.

A number of new technologies that enable high-throughput, cost-effective screening of potential drug candidates have been developed in recent years. Such compounds may be derived from the large proprietary collections held by pharmaceutical companies, from new synthetic approaches such as combinatorial chemistry, or from natural sources. The latter remain a major source of new chemicals: many are already used in human treatment and many others are currently undergoing evaluation as the potential medicines of the future.

Chemistry, Pharmaceutical↗

Synthesis of a biologically active fluorescent probe for labeling neurotensin receptors.

We synthesized a fluorescent derivative of the tridecapeptide neurotensin (NT), with the aim of providing a new tool for the pharmacological characterization and anatomic localization of NT receptors in mammalian brain. Fluoresceinylated NT (N alpha-fluoresceinyl thiocarbamyl (FTC)-[Glu1]NT; fluo-NT) was synthesized using solid-phase methodology and purified to 99% homogeneity by preparative high-pressure liquid chromatography (HPLC). Analytical HPLC, acidic and carboxypeptidase Y hydrolysis, and fast atom bombardment-mass spectroscopy confirmed that the purified compound was selectively labeled on the [Glu1] terminus and that a single FTC moiety was coupled to each molecule of [Glu1]NT. Flow cytometric analysis of the binding of fluo-NT to SN17 septal neuroblastoma cells indicated that the fluorescent derivative bound neural NT receptors with an affinity comparable to that of monoiodinated NT([125I]-NT). Competition experiments on mouse brain membrane preparations showed fluo-NT to inhibit specific [125I]-NT binding with a coefficient of inhibition (KI) virtually identical to that of the native peptide (0.67 vs 0.55 nM). Conventional epifluorescence and confocal microscopic analysis of specific fluo-NT binding to sections of the rat midbrain revealed a topographic distribution of the bound fluorescent ligand similar to that previously observed with autoradiography using [125I]-NT. However, fluo-NT provided markedly higher cell resolution and enabled, in particular, the detection of hitherto unnoted intracytoplasmic receptor clusters. Binding of fluo-NT to live SN17 hybrid cells indicated that the fluorescent ligand had retained its ability to internalize in vivo and confirmed that this internalization process was both time- and temperature-dependent. In sum, the present study demonstrates that fluo-NT is applicable to both the pharmacological study of NT binding sites using flow cytometry and to the regional and cellular localization of these sites by conventional epifluorescence and confocal microscopy.

Amino Acids↗

Demography, nursing and community care: a review of the evidence.

Demography is a most powerful influence upon social policy making. Policy making cannot be divorced from the constitution and the characteristics of the population for which it is intended. This paper commences by identifying and reviewing the most potent of those trends, and then examines the implications, first for the capacity of the community to cope with its dependents and then for the supply of nurses, before illustrating the importance of community nursing to government policies on community care.

Adult↗

You in Mind: a preventive mental health television series.

This study of BBC Television's 'You in Mind' series provides preliminary evidence for the benefits of a mass media approach to preventive mental health. The series was seen by a large national audience who appraised it positively. It had a greater impact in the area of understanding problems as opposed to seeing what to do about them, and a greater impact on the viewer's perceptions of the problems of people the viewers knew, as opposed to the problems of the viewers themselves. Measures of intentions to change behaviour, even when corrected for over-reporting, suggest that a significant minority of the audience had changed or intended to change their behaviour as a result of the series. However, no specific pre-post changes in coping or help-seeking were found. These findings are discussed in terms of the potential and limitations of the mass media for mental health promotion.

Adolescent↗

Receptor-based assays in screening for biologically active substances.

Molecular biology has identified new receptors and ligands which are deregulated in diseases such as cancer and autoimmune conditions and which provide rational targets for therapeutic intervention. Advances in instrumentation and methodology make it possible to screen large numbers of samples in simple receptor-ligand binding assays in the search for drug candidates. Caution must be exercised in the interpretation of data derived from such assays. This is particularly pertinent to the recently characterized receptors, such as the cytokine receptors, as we do not fully understand the relationship between the receptor type and the linkage of receptors to the appropriate or inappropriate second messenger systems that are used in the experimental screening protocols and the disease state.

Humans↗