The effects of bacterial products on airway cells and their function.
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Biomedical subjects
Publications and source records attributed to R Wilson.
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The acquisition of multiplication facts by 4 elementary students with learning disabilities was compared under two instructional delivery formats-teacher directed and computer assisted. The two interventions were compared in terms of opportunities to respond and success rate. All students mastered more facts in the teacher-directed condition. In addition, teachers provided many more opportunities to respond and showed a higher success rate than did the software program. Implications of teacher-directed and computer-assisted instruction are discussed in terms of efficacy and feasibility.
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Despite being regularly exposed to particulate matter during breathing, which contains bacteria from the commensal flora in the nasopharynx and from the environment, the healthy lung is kept sterile by efficient defence mechanisms. Bacterial infections of the respiratory mucosa represent a dynamic interaction, to which both host and bacterial factors contribute. The abnormal host defences associated with chronic respiratory infections (e.g. cystic fibrosis and other forms of bronchiectasis) serve to emphasize their permissive role. The bacteria that cause bronchial infections possess a wide array of potential virulence factors that contribute to their pathogenicity. Many of these factors influence the mucociliary system, an important first-line defence mechanism. The multiplication, spread and persistence of bacteria within the bronchial lumen, and consequent damage to the epithelium, stimulates a chronic inflammatory response, which also impairs mucociliary clearance and damages lung tissue. A greater understanding of host-bacterial interactions during mucosal infections should in the future lead to the development of new therapies and treatment strategies.
A potential role for the intestine of seawater-adapted teleosts in acid­base regulation was investigated following earlier reports of highly alkaline rectal fluids in the gulf toadfish Opsanus beta. Rectal samples taken from starved seawater-adapted rainbow trout had a high fluid pH (8.90±0.03; mean ± s.e.m., N=13) and base (HCO3-+2CO32-) content of 157±26 mequiv kg-1 (N=11). In trout fitted with rectal catheters, rectal fluid was voided at a rate of 0.47±0.11 ml kg-1 h-1 (N=8), giving a net base excretion rate of 114±15 µequiv kg-1 h-1 (N=7). Drinking rates averaged 3.12±0.48 ml kg-1 h-1 (N=8), and accounted for only 6 % of the base excreted via the intestine, indicating substantial net transport of endogenously derived base into the intestine. Rectally excreted base was approximately balanced by an equivalent efflux of net acid from non-rectal sources (possibly as NH4+ excretion via the gills). Samples taken from four sites along the intestine revealed that the most anterior region (the pyloric intestine) was responsible for the majority of HCO3-+2CO32- accumulation. The pyloric intestine was subsequently perfused in situ to investigate possible mechanisms of base secretion. Net base fluxes were found to be dependent on luminal Cl-, 76 % stimulated by amiloride, 20 % inhibited by 10(-4) mol l-1 acetazolamide, but unaffected by either 10(-4) mol l-1 SITS or 2x10(-5) mol l-1 DIDS. This suggests that the mechanism of base secretion within the pyloric intestine may involve a Cl-/HCO3--ATPase. It is speculated that intestinal base secretion may play a role in facilitating osmoregulation of seawater-adapted teleosts.
The aim of this study was to determine whether recurrent miscarriage (three or more miscarriages, no live children) was associated with an increased incidence of autoantibodies. Five groups were enrolled into the study; healthy non-pregnant women, healthy first-trimester pregnant women, women suffering spontaneous abortion, those undergoing termination of pregnancy and those with a previous history of miscarriage. The number of total B cells and the numbers of the antibody producing B cell subset CD5+/CD20+ were determined for each group. Samples were tested for anticardiolipin antibodies, antinuclear antibodies and thyroid microsomal and thyroglobulin antibodies. The results showed that compared to normal pregnancy or spontaneous abortion, recurrent miscarriage was associated with a significant increase in the number of CD5+/20+ positive cells (0.8 +/- 0.3 vs 0.5 +/- 0.1 vs 1.1 +/- 0.3 x 10(8)/l; p < 0.001). These women were also found to have a higher incidence of thyroid antibodies, with four out of the 11 patients being positive for thyroid microsomal antibodies. These results suggest that there may be an association between autoimmunity and recurrent miscarriage.
Previous studies have suggested that there may be a link between Turner's syndrome and autoimmunity. The numbers involved in these studies have tended to be small and few studies have included family members. This study has compared the incidence of thyroid antibodies in the serum of 60 patients with Turner' syndrome and 50 of their mothers with 127 controls. Total T4 and TSH levels were also measured. Of the 60 patients with Turner's syndrome 18 (30%) were positive for either thyroid peroxidase (TPO) and/or thyroglobulin antibodies. The peak incidence of thyroid antibodies occurred at 13 years of age. 11 (22%) of the mothers were also antibody positive. The incidence of thyroid antibodies was significantly higher in both the patients with Turner's Syndrome (30 vs 1.7% p < 0.001) and their mothers (22 vs 6.6% p < 0.05) than in the control groups. The increased incidence of thyroid antibodies found in these patients and their mothers confirms that there is an association between Turner's Syndrome and autoimmunity. However unlike previous studies we found more patients were positive for thyroglobulin than TPO antibodies.
OBJECTIVES: To assess what family physicians need to promote smoking cessation by looking at current knowledge, attitudes, and behaviours and to examine the barriers facing physicians in implementing an effective antismoking strategy. DESIGN: Cross-sectional study involving face-to-face interviews and mailed questionnaires. SETTING: Family practices in Kingston, Ont, and surrounding areas. PARTICIPANTS: All family physicians (n = 155) in the City of Kingston and the counties of Frontenac, Lennox, and Addington. MAIN OUTCOME MEASURES: Knowledge, attitudes, beliefs, and practices concerning smoking cessation; barriers and practices recommended in the literature. RESULTS: Response rate was 77%. Many physicians know about smoking cessation, and many actively counsel their patients to quit. Brief advice, nicotine replacement therapy, self-help materials, and follow-up appointments are the most common methods. Although many report that they are already knowledgeable, many are willing to learn more. Many physicians have unrealistically high estimates of the probability of success, and many find poor compliance among patients to be the greatest barrier. CONCLUSIONS: Family physicians in this are recognize the need to help their patients to quit and are identifying and counseling smokers in their practices. The main educational need could be to appreciate smoking as an addictive behaviour.
Morphine injected s.c. in the tail is a potent analgesic in the tail-flick assay when the radiant heat source is focused directly over the injection site (ED50, 4.5 micrograms), but not if the radiant heat source is moved 1 cm proximally or distally to the injection site. Naloxone given systemically reverses this peripheral analgesia. Antisense oligodeoxynucleotides directed against exons 1 and 4 of MOR-1, a cloned mu opioid receptor, administered intrathecally (i.t.) block the local analgesic effect of morphine in the tail, indicating that the local response is mediated through mu receptors located on the terminals of sensory neurons from the dorsal root ganglia. Combinations of morphine given locally in the tail and spinally (i.t.) are synergistic. Spinal morphine also synergizes with systemic morphine in analgesia assays. Supraspinal morphine enhances systemic morphine analgesia, but less dramatically. We also examined tolerance on these analgesic systems by using a daily morphine injection paradigm which shifts the dose-response curve for systemic morphine approximately 2-fold after 5 days. In this paradigm, morphine's analgesic potency after either supraspinal or spinal administration alone does not change. However, the dose-response curve for local morphine in the tail is shifted by over 19-fold. The analgesic activity of the combination of supraspinal and systemic morphine is lowered approximately 2-fold and the combination of i.t. and systemic morphine by 12-fold. These studies confirm the presence of a peripheral mechanism for morphine analgesia mediated by mu receptors located on sensory neurons from the dorsal root ganglia, which is extremely sensitive to chronic morphine dosing.
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We describe here a semi-permeabilized cell-system which reconstitutes the efficient synthesis, translocation, folding, assembly and degradation of membrane and secretory proteins. Cells grown in culture were treated with the detergent digitonin which selectively permeabilized the plasma membrane leaving the cellular organelles, such as the endoplasmic reticulum (ER) and trans-Golgi network intact. These permeabilized cells were added to an in vitro translation system, either wheatgerm or reticulocyte lysate, supplemented with RNA coding for either membrane or secretory proteins. Efficient translocation and modification of proteins by these cells was demonstrated by protease protection, photocross-linking of nascent chains to components of the translocation apparatus and by post-translational modifications such as glycosylation or hydroxylation. A comparison was made between the ability of semi-permeabilized cells and microsomal vesicles to fold and assemble proteins. The results show that the intact ER within these cells can assemble proteins much more efficiently than vesicularized ER. Furthermore, the semi-permeabilized cells carried out the redox-dependent degradation of tissue-type plasminogen activator. This system has all the advantages of conventional cell-free systems, including speed and, importantly, the ability to manipulate the components of the assay, while retaining intracellular organelles and, therefore, allowing cellular processes to occur as they would in the intact cell.
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The CMA's decision-making framework on core (i.e., publicly funded) and comprehensive health care services emphasizes flexibility and recognizes three levels at which decisions can be made: between patients and physicians (micro), in the community or by society (meso) and by governments (macro). Three major content dimensions are considered quality of care (e.g., effectiveness, appropriateness and efficiency of health care services), ethics (e.g., decisions that reflect fairness and acceptability to patients and physicians) and economics (e.g., measurement of service costs against economic benefits in a time of severe economic restraint). There are challenges in applying the framework; however, by providing decision-makers with the knowledge and tools needed to assist in the process, it is hoped that the first and foremost concern will continue to be the quality of patient care so highly valued by Canadians.
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The 4-hydroxy-2-alkylquinolines and their N-oxides are secondary metabolites produced by Pseudomonas aeruginosa which inhibit the growth of a number of Gram-positive organisms including Staphylococcus aureus. To facilitate the identification of these compounds in biological fluids, we have developed a rapid profiling system based on gas chromatography-electron-capture mass spectrometry of the O-bistrifluoromethylbenzoyl derivatives. Using the technique, over twenty hydroxyalkylquinolines have been identified from a culture obtained from a strain of P. aeruginosa obtained from a patient with severe bronchiectasis.