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Biomedical subjects

S Preston

Publications and source records attributed to S Preston.

At least 19 recordsLinked to original sources
PubMed2007

Beta-glucosylceramide: a novel method for enhancement of natural killer T lymphoycte plasticity in murine models of immune-mediated disorders.

BACKGROUND: beta-Glucosylceramide, a naturally occurring glycolipid, exerts modulatory effects on natural killer T (NKT) lymphocytes. AIM: To determine whether beta-glucosylceramide can alter NKT function in opposite directions, colitis was induced by intracolonic installation of trinitrobenzenesulphonic acid, and hepatocellular carcinoma (HCC) was induced by transplantation of Hep3B cells. METHODS: The immunological effect of beta-glucosylceramide was assessed by analysis of intrahepatic and intrasplenic lymphocyte populations, serum cytokines and STAT protein expression. RESULTS: Administration of beta-glucosylceramide led to alleviation of colitis and to suppression of HCC, manifested by improved survival and decreased tumour volume. The beneficial effects were associated with an opposite immunological effect in the two models: the peripheral:intrahepatic CD4:CD8 lymphocyte ratio increased in the colitis model and decreased in the HCC group. The peripheral:intrahepatic NKT lymphocyte ratio decreased in beta-glucosylceramide-treated mice solely in the HCC model. The effect of beta-glucosylceramide was associated with decreased STAT1 and 4 expression, and with overexpression of STAT6, along with decreased interferon gamma levels in the colitis model, whereas an opposite effect was noted in the HCC model. CONCLUSIONS: beta-glucosylceramide alleviates immunologically incongruous disorders and may be associated with "fine tuning" of immune responses, by changes in plasticity of NKT lymphocytes.

Animals↗
PubMed2006

Location of major histocompatibility complex class II molecules in rafts on dendritic cells enhances the efficiency of T-cell activation and proliferation.

The existence of major histocompatibility complex (MHC) class II molecules in lipid rafts has been described in dendritic cells (DC); however, the importance of rafts in T-cell activation has not been clarified. In this study, the distribution of the lipid raft components (CD59 and GM1 ganglioside) in human monocyte-derived DC was investigated. DC had an even distribution of these components at the cell surface. In addition, raft-associated GM1 ganglioside colocalized with cross-linked MHC class II. This implies coaggregation of raft components with these MHC molecules, which may be important in the interaction between T cells and antigen-presenting cells. In studies carried out to investigate the effect of the DC : T-cell interaction on raft distribution, we found a clustering of the lipid raft component CD59 on DC at the synaptic interface, with associated activation of the interacting T cell. In an antigen-specific response between DC and CD4+ T-cell clones, disruption of lipid rafts resulted in inhibition of both CD59 clustering and T-cell activation. This was most pronounced when limiting amounts of cognate peptide were used. Together, these data demonstrate the association of MHC class II with lipid rafts during DC : T-cell interaction and suggest an important role for DC lipid rafts in T-cell activation.

CD4-Positive T-Lymphocytes↗
PubMed2005

Single blind, randomised, comparative study of the Bug Buster kit and over the counter pediculicide treatments against head lice in the United Kingdom.

OBJECTIVE: To compare the effectiveness of the Bug Buster kit with a single treatment of over the counter pediculicides for eliminating head lice. DESIGN: Single blind, multicentre, randomised, comparative clinical study. SETTING: Four counties in England and one county in Scotland. PARTICIPANTS: 133 young people aged 2-15 years with head louse infestation: 56 were allocated to the Bug Buster kit and 70 to pediculicide treatment. INTERVENTIONS: Home use of proprietary pediculicides (organophosphate or pyrethroid) or the Bug Buster kit. MAIN OUTCOME MEASURE: Presence of head lice 2-4 days after end of treatment: day 5 for the pediculicides and day 15 for the Bug Buster kit. RESULTS: The cure rate using the Bug Buster kit was significantly greater than that for the pediculicides (57% v 13%; relative risk 4.4, 95% confidence interval 2.3 to 8.5). Number needed to treat for the Bug Buster kit compared with the pediculicides was 2.26. CONCLUSION: The Bug Buster kit was the most effective over the counter treatment for head louse infestation in the community when compared with pediculicides.

Adolescent↗
PubMed2004

Implementing intensive insulin therapy: development and audit of the Bath insulin protocol.

Intensive insulin therapy to control blood glucose has been found to reduce mortality among critically ill patients in a surgical intensive care unit, though a simple prescriptive insulin infusion protocol to achieve this has not been published previously. This study documents the development and routine use of a simple prescriptive intravenous insulin infusion protocol for critically ill patients and compares the results with previous practice. During development the protocol was optimized and practical issues of implementation addressed. The optimized protocol was then used for all ICU admissions, and a prospectively defined retrospective chart audit performed for the first month of use. Results were compared with a similar time period the previous year. In September 2002, 27 admissions were started on the protocol. Blood glucose for the time on the protocol had a median value of 6.2 (IQR 5.9-7.1) mmol/l compared with 9.2 (IQR 8.1-10.2) mmol/l for those on insulin in 2001. Blood glucose for the whole ICU stay for those on the protocol in 2002 had a median value of 6.6 (IQR 6.0-7.4) mmol/l compared with 8.6 (IQR 8.0-9.4) mmol/l in 2001. Blood glucose for all ICU patients in 2002 had a median value of 6.5 (IQR 6.0-7.3) mmol/l compared with 7.2 (IQR 6.3-8.3) mmol/l in 2001. Three blood glucose recordings were less than 2.2 mmol/l in September 2002. This study provides initial effectiveness and safety data for the Bath Insulin Protocol Further audits in a larger patient population are now needed.

Blood Glucose↗
PubMed2002

Predicting arsenic solubility in contaminated soils using isotopic dilution techniques.

An isotopic dilution assay was developed to measure radiolabile As concentration in a diverse range of soils (pH 3.30-7.62; % C = 1.00-6.55). Soils amended with 50 mg of As kg(-1) (as Na2HAsO4 x 7H2O) were incubated for over 800 d in an aerated "microcosm" experiment. After 818 d, radiolabile As ranged from 27 to 57% of total applied As and showed a pH-dependent increase above pH 6. The radiolabile assay was also applied to three sets of soils historically contaminated with sewage sludge or mine-spoil. Results reflected the various geochemical forms in which the arsenic was present. On soils from a sewage disposal facility, radiolabile arsenate ranged from 3 to 60% of total As; mean lability was lower than in the equivalent pH range of the microcosm soils, suggesting occlusion of As into calcium phosphate compounds in the sludge-amended soils. In soils from mining areas in the U.K. and Malaysia, radiolabile As accounted for 0.44-19% of total As. The lowest levels of lability were associated with extremely large As concentrations, up to 17,000 mg kg(-1), from arsenopyrite. Soil pore water was extracted from the microcosm experiment and speciated using "GEOCHEM". The solid<==>solution equilibria of As in the microcosm soils was described by a simple model based on competition between HAsO4(2-) and HPO4(2-) for "labile" adsorption sites.

Arsenic↗
PubMed2001

Use of bacterial biosensors to interpret the toxicity and mixture toxicity of herbicides in freshwater.

The dose response relationship between seven commonly used herbicides and four luminescence-based bacterial biosensors was characterised. As herbicide concentration increased the light emitted by the test organism declined in a concentration dependent manner. These dose responses were used to compare the predicted vs. observed response of a biosensor in the presence of multiple contaminants. For the majority of herbicide interactions, the relationship was not additive but primarily antagonistic and sometimes synergistic. These biosensors provide a sensitive test and are able to screen a large volume and wide range of samples with relative rapidity and ease of interpretation. In this study biosensor technology has been successfully applied to interpret the interactive effects of herbicides in freshwater environments.

Bacteria↗
PubMed2001

Soil solution extraction techniques for microbial ecotoxicity testing: a comparative evaluation.

The suitability of two different techniques (centrifugation and Rhizon sampler) for obtaining the interstitial pore water of soil (soil solution), integral to the ecotoxicity assessment of metal contaminated soil, were investigated by combining chemical analyses and a luminescence-based microbial biosensor. Two different techniques, centrifugation and Rhizon sampler, were used to extract the soil solution from Insch (a loamy sand) and Boyndie (a sandy loam) soils, which had been amended with different concentrations of Zn and Cd. The concentrations of dissolved organic carbon (DOC), major anions (F- , CI-, NO3, SO4(2-)) and major cations (K+, Mg2+, Ca2+) in the soil solutions varied depending on the extraction technique used. Overall, the concentrations of Zn and Cd were significantly higher in the soil solution extracted using the centrifugation technique compared with that extracted using the Rhizon sampler technique. Furthermore, the differences observed between the two extraction techniques depended on the type of soil from which the solution was being extracted. The luminescence-based biosensor Escherichia coli HB101 pUCD607 was shown to respond to the free metal concentrations in the soil solutions and showed that different toxicities were associated with each soil, depending on the technique used to extract the soil solution. This study highlights the need to characterise the type of extraction technique used to obtain the soil solution for ecotoxicity testing in order that a representative ecotoxicity assessment can be carried out.

Biological Assay↗
PubMed2000

Measuring symptom change in patients with Parkinson's disease.

BACKGROUND: The 39-item Parkinson's disease questionnaire (PDQ-39) is more sensitive to functional change than other measures of health and disability. AIM: To determine the ability of this scale to change over time and the concurrent validity of some of its subscales. METHODS: We assessed a cohort of 67 Parkinson's patients for 18 months, using the PDQ-39, the GHQ-28 general health questionnaire and the Office of Population and Census Surveys disability instrument. RESULTS: The Office of Population and Census Surveys disability instrument and GHQ-28 recorded no significant change, but the PDQ-39 showed marked changes in levels of functioning. We also analysed changes on the PDQ-39 subscales as well as concurrent validity data for several subscales. This showed concurrent validity with the Beck depression and anxiety inventories, the Barthel index and the Royal Postgraduate Medical School severity scale. There was a high level of concurrent validity for all comparisons except for the Barthel index. CONCLUSION: The PDQ-39 is a sensitive tool for monitoring change in patients with Parkinson's disease. It has high levels of concurrent validity with established measures of mood and motor function.

Activities of Daily Living↗
PubMed1997

The leukocyte/neuron cell surface antigen OX2 binds to a ligand on macrophages.

The OX2 membrane glycoprotein contains two immunoglobulin superfamily (IgSF) domains and seems likely to interact with other cell surface proteins. A soluble chimeric protein with the two IgSF domains of OX2 engineered onto domains 3 + 4 of rat CD4 antigen was expressed. To detect possible weak interactions, the chimeric protein was coupled to fluorescent covaspheres to provide a highly avid display of OX2. The OX2 covaspheres bound macrophages but not other cell types. The specificity of the interaction was demonstrated by blocking with Fab fragments of the OX2 monoclonal antibody (mAb). A new mAb, MRC OX88, was raised against macrophages which also blocked the interaction and presumably recognizes the ligand. The epitope for the MRC OX2 mAb and a site for ligand binding were mapped to domain 1 by site-directed mutagenesis. The OX2 antigen is present on thymocytes, some lymphocytes, neurons and endothelial cells; thus, it has the potential to mediate interactions between these cell types and macrophages.

Amino Acid Sequence↗
PubMed1997

The use of administrative data to risk-stratify asthmatic patients.

In this article, a simple methodology to risk-stratify asthmatics is presented and validated. Such a model can be used to identify those high risk and more severely ill asthmatics who could benefit the most from case management and increased educational efforts. Using logistic regression, the model was created to predict the probability of an asthma-related admission among all asthmatics who were members of a large HMO during calendar year 1994 (N = 54,573). The model used data from pharmacy, laboratory, and specialist claims, as well as encounter and demographic data available in U.S. Healthcare's administrative database. A member's prior asthma-specific utilization patterns, pharmaceutically determined severity of illness, and length of enrollment in the managed care organization had the most influence on the equation. A cross-validation of the model confirms how administrative data can be used to accurately risk-stratify those with a chronic disease. Finally, some additional research possibilities associated with the identification of high risk subscribers using only administrative data are outlined.

Adult↗
PubMed1996

Health plan satisfaction and risk of disenrollment among social/HMO and fee-for-service recipients.

Health plan satisfaction among the elderly is affected by multiple individual and locational factors. We used a general behavioral framework of predisposing, enabling, and service use factors to produce adjusted satisfaction scores. These then were included in a logistic analysis to determine the effect of satisfaction on continued membership in social health maintenance organizations (S/HMOs) or continued participation in fee-for-service care. S/HMO members, after one year in the plan, generally reported satisfaction scores comparable to Medicare beneficiaries in fee-for-service care. Satisfaction with perceived physician quality and interpersonal relationships with the providers reduced the risk of disenrollment. Functional impairment reduced the likelihood of disenrollment, but this effect varied by community. Being impaired was protective in communities with established HMOs. In markets where HMOs were emerging or where intensive HMO competition was beginning, disability increased the likelihood of changing current coverage. S/HMO membership, after adjusting for the market area's general disenrollment propensities, had varying effects. Being a newly formed plan was not a consistent predictor of higher disenrollment rates.

Aged↗
PubMed1996

Clinical hypertension in Native Americans: a comparison of 1987 and 1992 rates from ambulatory care data.

THE AUTHORS EXAMINED THE PREVALENCE of clinically diagnosed hypertension among all American Indian and Alaska Native outpatients served in Indian Health Service (IHS) facilities in fiscal year 1992, and compared these rates with a similar analysis done in 1987. In this report they provided data on that analysis as well as on the association between hypertension and diabetes. The 1992 overall estimated age-adjusted prevalence of clinically diagnosed hypertension in adults older than age 15 was 10.4%, compared with 10.9% in 1987, a small but significant decrease. Considerable variation exists in hypertension prevalence rates in American Indian communities as analyzed by IHS service area. This report represents an attempt to use ambulatory patient care data to demonstrate a means for ongoing surveillance of a chronic disease for the entire service population of the IHS. This comprehensive data set represents approximately 60% of the entire U.S. American Indian and Alaska Native population. Based on the ongoing nature of this ambulatory patient care data system, this model for hypertension surveillance permits a unique opportunity for longitudinal evaluation of quality improvement efforts for the American Indian and Alaska Native populations served by the IHS.

Adolescent↗
PubMed1995

A sensitive assay for detecting low-affinity interactions at the cell surface reveals no additional ligands for the adhesion pair rat CD2 and CD48.

The ligand for the T cell antigen CD2 is CD48 in rodents, but CD58 in humans. The extracellular parts of these three antigens are structurally related in that all contain two immunoglobulin superfamily (IgSF) domains. There have been reports of alternative ligands for CD2 in the human, but not so far in rodents. We describe the analysis of ligands for rat CD2 and CD48 using fluorescent beads capable of displaying a high ligand density and detecting low-affinity interactions like that of CD2 with CD48 (Kd = 60-90 microM). Monovalent chimeric proteins containing the two IgSF domains of rat CD48 or CD2 and domains 3 and 4 of rat CD4 (CD4d3+4) were anchored to fluorescent covaspheres via a CD4 monoclonal antibody (mAb) with the CD48 or CD2 domains available for ligand binding. Multivalent CD48-CD4d3+4 covaspheres gave strong specific binding to rat CD2 expressed on the surface of transfected Jurkat cells. CD48-CD4d3+4 was compared with CD48-IgG and CD48-IgM as tools for detecting binding at the cell surface. Soluble divalent CD48-IgG and decavalent CD48-IgM bound to soluble CD2 with a Koff of around 10(-3) s-1 as determined using a BIAcore biosensor. However, binding to cells by CD48-IgG and CD48-IgM was only detectable when they were immobilized on covaspheres and represented no increase in sensitivity over CD48-CD4 covaspheres when tested for binding to cells expressing high and low levels of CD2. CD48-CD4d3+4 covaspheres only bound to rat cells expressing CD2. In the reverse orientation, bindign of CD2-CD4d3+4 covaspheres was dependent on expression of CD48. Pre-incubation of cells with CD2 or CD48 mAb abolished all binding of CD48-CD4d3+4 or CD2-CD4d3+4, respectively. The data provide no evidence for an alternative ligand for rat CD2 or CD48.

Animals↗