Search PubMed⌕ Search

Biomedical subjects

R Wilson

Publications and source records attributed to R Wilson.

At least 127 records · Page 7Linked to original sources
PubMed2000

Fringe is a glycosyltransferase that modifies Notch.

Notch receptors function in highly conserved intercellular signalling pathways that direct cell-fate decisions, proliferation and apoptosis in metazoans. Fringe proteins can positively and negatively modulate the ability of Notch ligands to activate the Notch receptor. Here we establish the biochemical mechanism of Fringe action. Drosophila and mammalian Fringe proteins possess a fucose-specific beta1,3 N-acetylglucosaminyltransferase activity that initiates elongation of O-linked fucose residues attached to epidermal growth factor-like sequence repeats of Notch. We obtained biological evidence that Fringe-dependent elongation of O-linked fucose on Notch modulates Notch signalling by using co-culture assays in mammalian cells and by expression of an enzymatically inactive Fringe mutant in Drosophila. The post-translational modification of Notch by Fringe represents a striking example of modulation of a signalling event by differential receptor glycosylation and identifies a mechanism that is likely to be relevant to other signalling pathways.

Animals↗
PubMed2000

Study of exclusive radiative B meson decays

We have studied exclusive, radiative B meson decays to charmless mesons in 9.7x10(6) B&Bmacr; decays accumulated with the CLEO detector. We measure B(B0-->K(*0)(892)gamma) = (4.55(+0.72)(-0. 68)+/-0.34)x10(-5) and B(B+-->K(*+)(892)gamma) = (3.76(+0.89)(-0. 83)+/-0.28)x10(-5). We have searched for CP asymmetry in B-->K(*)(892)gamma decays and measure A(CP) = +0.08+/-0.13+/-0.03. We report the first observation of B-->K(*)(2)(1430)gamma decays with a branching fraction of (1.66(+0.59)(-0.53)+/-0.13)x10(-5). No evidence for the decays B-->rhogamma and B0-->omegagamma is found and we limit B(B-->(rho/omega)gamma)/B(B-->K(*)(892)gamma)<0.32 at 90% C.L.

Journal Article↗
PubMed2000

Effects of hospitalists on cost, outcomes, and patient satisfaction in a rural health system.

PURPOSE: Previous studies have examined the effects of hospitalists in urban academic hospitals. We compared the outcomes of patients treated by hospitalists with those of patients treated by internists at a 647-bed rural community hospital. SUBJECTS AND METHODS: The 443 patients in the hospitalists' 10 most common diagnosis-related groups (DRGs) were compared with 1,681 patients in the same DRGs who were cared for by internists in fiscal year 1998. Length of stay, cost of care, patient illness severity, patient satisfaction, 30-day readmission rate, inpatient mortality, discharge status, and resource utilization were compared. RESULTS: The hospitalists' patients had a shorter mean (+/- SD) length of stay (4.1 +/- 3.0 days versus 5.5 +/- 4.9 days, P <0.001) and their cost of care was less than that of the internists' patients ($4,098 +/- $2,455 versus $4,658 +/- $4,084, P <0.001). Analyses that adjusted for patient age, race, sex, insurance status, severity of illness, and specific medical comorbidities confirmed these differences. The differences between hospitalists and internists were most apparent among very ill patients. Mortality rates were similar (4.5% for hospitalists versus 4.9% for internists, P = 0.80), as were the readmission rates (4.5% for hospitalists versus 5.6% for internists, P = 0.41). Patient satisfaction was similar for both groups. The internists used more resources in 8 of 11 categories. CONCLUSIONS: The hospitalists provided cost-effective care, particularly for the sickest patients, with good outcomes and patient satisfaction.

Health Resources↗
PubMed2000

Effect of lysozyme on the lectin-mediated phagocytosis of Bacillus cereus by haemocytes of the cockroach, Blaberus discoidalis.

Lysozyme-like activity has been demonstrated in both cell-free haemolymph and, more abundantly, in haemocyte-lysate supernatants of Blaberus discoidalis. This activity was non-inducible, but heat-stable, with a maximum activity at pH 6.2. When B. cereus was pre-incubated in a concentration of chicken egg-white lysozyme equivalent to the concentration of lysozyme-like activity in cell-free haemolymph, the phagocytosis of B. cereus opsonized with GlcNAc-specific lectins, i.e. BDL2, WGA and HPA, was significantly reduced by up to 50%, while phagocytosis of B. cereus opsonized with mannose-specific lectins, such as BDL1 and Con A, was significantly increased. Pre-incubation of B. cereus in a higher concentration of lysozyme resulted in a smaller, shorter lived increase in the phagocytic rate of bacteria opsonized with these mannose-specific lectins. The action of lysozyme on the peptidoglycan in the cell wall of B. cereus probably resulted in a reduction in the number of binding sites for the GlcNAc-specific lectins, and, therefore, reduced the phagocytic rate of BDL2, HPA and WGA-opsonized B. cereus. Concomitantly, the breakdown of peptidoglycan probably exposed mannose-containing polysaccharides, previously embedded in the peptidoglycan layer, resulting in an increase in the phagocytic rate of the BDL1- and Con A-opsonized B. cereus. These results are discussed in relation to the immune-potential of B. discoidalis.

Journal Article↗
PubMed2000

Laser modulation of angiogenic factor production by T-lymphocytes.

BACKGROUND AND OBJECTIVE: In previous investigations, small variations in the energy densities of low level light therapy (LLLT) were found to produce significant differences in the proliferation of resting T-lymphocytes in vitro. Pulsing these cells with mitogen in addition to laser therapy produced inhibitory effects regardless of the amplitude of the energy density used. In the current study, the effect of LLLT on the production of angiogenic factor(s) by T-lymphocytes was investigated in vitro. STUDY DESIGN/MATERIALS AND METHODS: Human T-cells isolated from peripheral blood were prepared in suspension either with or without addition of mitogen. Cell suspensions were irradiated with laser by using the following energy densities: 1.2, 3.6, 6.0, and 8.4 J/cm(2). Wavelength, pulsing frequency, and power output were kept constant at 820 nm, 5,000 Hz, and 50 mW, respectively. After either 3 or 5 days of incubation, lymphocyte supernatants were collected and added as conditioned media to cultured endothelial cells (ECs). The effect on the proliferation of these ECs was assessed over a 72-hour period by using a methylene blue assay. RESULTS: Endothelial cell proliferation increased significantly when incubated with conditioned media collected from resting T-cells exposed to 1.2 and 3.6 J/cm(2). Day 5 conditioned media produced similar patterns of EC proliferation to that of day 3 but at lower magnitude. Pulsing of T-lymphocytes with mitogen in addition to laser irradiation significantly lessened their angiogenic capability. Conditioned media from 3.6 J/cm(2) laser-treated T-cells induced the maximal EC proliferation in all groups studied. CONCLUSION: It would seem that laser therapy stimulates lymphocytes to produce factor(s) that can modulate EC proliferation in vitro; this effect on the lymphocytes is influenced by (1) the amplitude of energy density used for T-cell irradiation, (2) exposing T-cells to both mitogen and laser, and (3) the duration of T-cell incubation in culture.

Angiogenesis Inducing Agents↗
PubMed2000

Hemispheric differences in hippocampal volume predict verbal and spatial memory performance in patients with Alzheimer's disease.

Atrophy of the hippocampal formation, a region important for the acquisition of new declarative knowledge, has been well-documented in Alzheimer's disease (AD), although the relation of such atrophy to the extent of memory dysfunction in these patients has been less clear. In the present study, 18 patients with a clinical diagnosis of probable AD were studied with a high-resolution, quantitative magnetic resonance imaging (MRI) protocol, as well as the verbal and spatial versions of the Buschke controlled learning task. The volumes of the hippocampal formation and, as a control for generalized atrophy, parahippocampal gyrus and temporal neocortex were computed from gapless coronal slices taken perpendicular to the long axis of the hippocampus. To correct for individual differences in brain size, volumes of regions of interest were divided by total intracranial volume. Separate stepwise regression analyses (with age, right and left hippocampal, parahippocampal gyrus, and temporal lobe volumes as the independent variables) showed that left hippocampal volume was the best predictor of free recall and delayed free recall of verbal information (P = 0.0042 and P < 0.0001, respectively). Recall and delayed recall of the spatial location of verbal items were best predicted by right hippocampal volume (P = 0.0054 and P = 0.0118, respectively). Memory scores did not correlate either with parahippocampal gyrus or temporal lobe volume. Furthermore, the relation between hippocampal volume and memory function observed in cases with AD did not hold for healthy aged control subjects.

Aged↗
PubMed2000

The evolution of postcopulatory displays in dabbling ducks (Anatini): a phylogenetic perspective.

Although postcopulatory displays are widespread in animals, little is known about their function or the intended receiver. The postcopulatory displays of dabbling ducks are among the best described for any animal group. We documented the presence of initial and additional postcopulatory displays in nearly all dabbling duck species. We then reconstructed the evolution of postcopulatory displays in dabbling ducks using a phylogeny derived from mitochondrial DNA sequences. The display immediately following copulation (the initial display) is highly stereotyped in most species and shows extreme phylogenetic conservation. In contrast, the performance of additional displays is less stereotyped and less phylogenetically conservative. We review the possible functions of postcopulatory displays. Using evidence from display orientation, display form and phylogenetic reconstruction, we suggest that the most likely functions of postcopulatory displays in dabbling ducks are pair bond maintenance, individual identification, or signalling a successful copulation. Copyright 2000 The Association for the Study of Animal Behaviour.

Journal Article↗
PubMed2000

CGS 21680, dibutyryl cyclic AMP and rolipram attenuate the pro-inflammatory interactions of the Pseudomonas aeruginosa -derived pigment, 1-hydroxyphenazine, with human neutrophils.

The effects of the intracellular adenosine 3':5' cyclic monophosphate (cAMP)-elevating agents, CGS 21680 (0.01- 1 microM) and rolipram (0.01-1 microM), as well as those of dibutyryl cAMP (0. 05-4 mM) on the pro-inflammatory interactions of the P. aeruginosa -derived pigment, 1-hydroxyphenazine (1-hp, 3.1 and 12.5 microM), with human neutrophils have been investigated in vitro. Ca(2+)fluxes in FMLP-activated neutrophils were measured using a fura-2/AM spectrofluorimetric procedure, while a colourimetric method was used to measure release of the primary granule enzyme, elastase, from the cells. Treatment with 1-hp resulted in delayed clearance of Ca(2+)from the cytosol of N -formyl- L -methionyl- L -leucyl- L -phenylalanine (FMLP, 1 microM)-activated neutrophils and increased release of elastase. All 3 test agents caused dose-related antagonism of 1-hp-mediated potentiation of elastase release from activated neutrophils, which was associated with restoration of Ca(2+)homeostasis. These observations demonstrate the potential of cAMP-elevating agents, acting on Ca(2+)clearance mechanisms in activated neutrophils, to attenuate the potentially harmful pro-inflammatory effects of 1-hp.

Adenosine↗
PubMed2000

Quantitative analysis of long-chain trans-monoenes originating from hydrogenated marine oil.

Gas chromatography (GC) is used for the analysis of trans-fatty acids in partially hydrogenated vegetable oils. Although trans-isomers of C18 carbon length predominate in partially hydrogenated vegetable oils, trans-isomers of C20 and C22 carbon length occur in partially hydrogenated fish oil. We report a simple silver ion chromatographic combined with capillary GC technique for quantitative analysis of trans-monoenes derived from partially hydrogenated fish oil. Silver nitrate thin-layer chromatographic (TLC) plates are developed in toluene/hexane (50:50, vol/vol). Fatty acid methyl esters are separated into saturates (Rf 0.79), trans-monoenes (Rf 0.49), cis-monoenes (Rf 0.27), dienes (Rf 0.10), and polyunsaturated fatty acids with three or more double bonds remaining at the origin. The isolated trans-monoenes are quantitatively analyzed by capillary GC. The technique of argentation TLC with GC analysis of isolated methyl esters is highly reproducible with 4.8% variation (i.e., coefficient of variation, CV%) in R. values and 4.3 and 6.9% CV% in quantification within batch and between batch, respectively. Furthermore, the combined technique revealed that direct GC analysis underestimated the trans-content of margarines by at least 30%. In this study, C20 and C22 trans-monoenes were found in relatively large quantities; 13.9% (range 10.3-19.6%) and 7.5% (range 5.3-11.5%), respectively, in margarine purchased in 1995, but these C20 and C22 trans-monoenes were much reduced (0.1%) in a fresh selection of margarine purchased in 1998. Compositional data from labels underestimated the trans-content of margarines, especially those derived from hydrogenated marine oil. Low levels of C20 transmonoenes (range 0.1-0.3%) and C22 trans-monoenes (range 0.0-0.1%) were identified in adipose tissue obtained from healthy volunteers in 1995, presumably indicating consumption of partially hydrogenated fish oil.

Adipose Tissue↗
PubMed2000

Evidence of a T(H) 1 type response associated with recurrent miscarriage.

OBJECTIVE: To determine whether the T(H) 1 cytokine interferon (IFN)-gamma is associated with miscarriage whereas the T(H) 2 cytokine interleukin (IL)-10 is associated with successful pregnancy. DESIGN: Controlled clinical study. SETTING: Healthy volunteers in an academic setting. PATIENT(S): Group 1 comprised 10 nonpregnant women; group 2, 10 first-trimester primigravid women; group 3, 10 first-trimester primigravid women suffering spontaneous abortion; and group 4, 10 first-trimester pregnant women with a history of miscarriage. All women were pregnant at the time of sampling, but 5 miscarried later in the first trimester. INTERVENTION(S): None of the patients received any medication. MAIN OUTCOME MEASURE(S): Serum levels of IL-10 and IFN-gamma. RESULT(S): Levels of IL-10 were significantly raised in normal pregnancy. Levels of IFN-gamma were raised in the recurrent-miscarriage group as compared with normal pregnancy. When patients in group 4 were divided into those whose pregnancies went to term and those who miscarried, we found that successful pregnancy was associated with a statistically significant increase in IL-10, whereas miscarriage was associated with significantly increased levels of IFN-gamma. CONCLUSION(S): These results support the view that miscarriage is associated with a T(H) 1 type response.

Abortion, Habitual↗
PubMed2000

The role of Mycobacterium avium complex fibronectin attachment protein in adherence to the human respiratory mucosa.

Mycobacterium avium complex (MAC) are opportunistic respiratory pathogens that infect non-immunocompromised patients with established lung disease, although they can also cause primary infections. The ability to bind fibronectin is conserved among many mycobacterial species. We have investigated the adherence of a sputum isolate of MAC to the mucosa of organ cultures constructed with human tissue and the contribution of M. avium fibronectin attachment protein (FAP) to the process. MAC adhered to fibrous, but not globular mucus, and to extracellular matrix (ECM) in areas of epithelial damage, but not to intact extruded cells and collagen fibres. Bacteria occasionally adhered to healthy unciliated epithelium and to cells that had degenerated exposing their contents, but never to ciliated cells. The results obtained with different respiratory tissues were similar. Two ATCC strains of MAC gave similar results. There was a significant reduction (P < 0.05) in the number of bacteria adhering to ECM after preincubation of bacteria with fibronectin and after preincubation of the tissue with M. avium FAP in a concentration-dependant manner. The number of bacteria adhering to fibrous mucus was unchanged. Immunogold labelling demonstrated fibronectin in ECM as well as in other areas of epithelial damage, but only ECM bound FAP. A Mycobacterium smegmatis strain had the same pattern of adherence to the mucosa as MAC. When the FAP gene was deleted, the strain demonstrated reduced adherence to ECM, and adherence was restored when the strain was transfected with an M. avium FAP expression construct. We conclude that MAC adheres to ECM in areas of epithelial damage via FAP and to mucus with a fibrous appearance via another adhesin. Epithelial damage exposing ECM and poor mucus clearance will predispose to MAC airway infection.

Adenoids↗
PubMed2000

Interaction of Bordetella pertussis with human respiratory mucosa in vitro.

The human respiratory tract pathogen Bordetella pertussis is the major cause of whooping cough in infants and young children, and also causes chronic cough in adults. B. pertussis infection damages ciliated epithelium in the respiratory tract. However, the interaction of the bacterium with the respiratory mucosa is poorly understood, and previous studies have either utilized animal tissue which may not be appropriate, or isolated cell systems which lack the complexity of the respiratory mucosa. We have studied the interaction of B. pertussis strain BP536 with human nasal turbinate tissue in an air-interface organ culture over 5 days. We have also compared infection by BP536 with two other strains, Tohama I and CN2992, to determine whether the interactions observed with BP536 are consistent, and, in both nasal turbinate and adenoid organ cultures at 24 h, to determine whether there were differences between tissue from different parts of the respiratory tract. BP536 adhered to cilia, most commonly at their base, and disorganized their spatial arrangement, they also adhered to damaged tissue and mucus, but very rarely to unciliated cells. Within the first 24 h there was a five-fold increase in bacterial density on ciliated cells, and the total number of adherent bacteria increased up to 96 h. Infection caused increased mucus at 24h and an increase in damaged epithelium from 72 h which involved both ciliated and unciliated cells. The number of residual ciliated cells did not decrease after 72 h. The three different strains of B. pertussis exhibited similar interactions with the mucosa, and there was no tissue specificity for adenoid or turbinate tissue. We conclude that B. pertussis adhered to multiple sites on the mucosa and caused hypersecretion and epithelial damage which are the pathological changes described in vivo.

Adenoids↗
PubMed2000

Introduction: the role of bacterial infection in chronic bronchitis.

Acute exacerbations of chronic bronchitis reflect increased airway inflammation and are characterised by one or more symptoms of increased sputum production, sputum purulence, and breathlessness. The causes are multifactorial, and bacterial infection is involved in about half of cases. A proportion of patients also have chronic colonization of the bronchial tree between exacerbations, and this may act as a stimulant of airway inflammation. Colonization represents a balance in which compromised host defences limit bacterial numbers but do not eradicate them. The balance is upset during an exacerbation, often due to extraneous factors such as a viral infection or air pollution, leading to increased bacterial numbers and consequently more inflammation. In patients with severe airway damage, infective exacerbations are more likely to occur, and serious consequences may result if baseline lung function is impaired or there are comorbid conditions. In these circumstances, the exacerbation is less likely to resolve spontaneously. Antibiotic treatment benefits patients by achieving bacterial eradication and resolution of the inflammatory response. However, since superficial mucosal infections may resolve spontaneously, there are serious concerns about widespread antibiotic use in patients with more trivial illness. Future studies should include better definition of the type of patients enrolled, improved techniques to determine bacteriological response, and better outcome measures.

Anti-Bacterial Agents↗
PubMed2000

Evidence of bacterial infection in acute exacerbations of chronic bronchitis.

The frequency with which bacterial infection causes exacerbations of chronic obstructive pulmonary disease (COPD) may depend on the dominant pathology present; patients with chronic bronchitis are more susceptible to bacterial bronchial infections than those at the emphysema or asthma ends of the spectrum. However, impairment in respiratory function may be very important in governing the outcome of an exacerbation. Placebo-controlled trials have provided conflicting evidence of the efficacy of antibiotics in acute exacerbations. Overall, there is a significant benefit, particularly in certain patient groups, defined by symptoms and past history. Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis are the species most commonly isolated during exacerbations, and the same species may colonize the bronchial mucosa when the patient is in a stable state. Evidence is accumulating that bacteria are an independent stimulus of mucus hypersecretion and bronchial inflammation, and that they interact with other stimuli such as viral infection, atmospheric pollution, and tobacco smoke. New approaches are being used to investigate the importance of bacterial infection in patients with COPD. There are several good reasons why new more potent antibiotics might be expected to be superior to older standard compounds in the management of patients with problematic COPD. However, future studies should aim to confirm that bacteriologic superiority translates into improved clinical outcomes, and seek to measure the level of benefit.

Acute Disease↗
PubMed2000

Results of testing for anti-GM1 antibodies.

We used an ELISA technique to measure IgG and IgM antibodies to the ganglioside GM1, with the results expressed in arbitrary units. We tested 1007 sera from patients with peripheral neuropathy or muscle weakness. For IgG and IgM antibodies, the distribution of results differed significantly from a normal distribution. In the patient group, 81 of 1007 sera had elevated levels of IgG antibodies (> 10 units). Of these, 11 patients had very high levels (> 50 units). These 11 patients had diagnoses of GBS (4), motor neurone disease (3) or non-specific idiopathic neuropathy (4). For IgM antibodies, 115 of 1007 sera were positive (> 20 units). Of these, 18 patients had very high levels (> 50 units). These 18 patients had diagnoses of Guillain-Barré syndrome or Miller Fisher syndrome (4), multifocal motor neuropathy (4), motor neurone disease (2), non-specific neuropathy (2). We conclude that anti-GM1 antibodies in high titre are uncommon. Patients with multifocal motor neuropathy have high levels of antibody. However, patients with other disorders may also have high levels, so that anti-GM1 antibody levels alone are not a specific test for multifocal motor neuropathy. We found that antibodies to GM1 were present in the sera of patients with chronic idiopathic neuropathy, leading us to suggest that these antibodies may sometimes arise as a secondary response to disease.

Adult↗
PubMed2000

Did Project 2000 nurse training change recruitment patterns or career expectations?

In the UK, Project 2000 nurse education, introduced over the last eight years, aimed to increase the professional status of nurses and enhance skills, focusing on wider community care. This paper reports some of the results from a research project conducted between 1994 and 1996, funded by the Department of Health (Project 2000 Fitness for Purpose 1996). It was hypothesized that the changes in Project 2000 training might attract those more academically qualified and lead to more rapid career progression. The results found in this study did not support either of these hypotheses and suggestions are made about the reasons for the negative findings.

Adult↗