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Biomedical subjects

R J Shaw

Publications and source records attributed to R J Shaw.

At least 145 records · Page 8Linked to original sources
PubMed1985

Nedocromil, a mucosal and connective tissue mast cell stabilizer, inhibits exercise-induced asthma.

Nedocromil, the disodium salt of a pyranoquinoline dicarboxylic acid, has a similar profile of activity to disodium cromoglycate (DSCG) but appears to be more active in stabilizing mucosal-type mast cells. In a double-blind placebo-controlled trial nedocromil (2 mg) was given by inhalation to eight asthmatic patients prior to a treadmill exercise task. There was a significant reduction in the fall in FEV1 (P less than 0.01) and FVC (P less than 0.05) after nedocromil when compared to placebo. This study indicates that nedocromil might be an effective anti-asthma agent and in addition may help define the role of the mucosal mast cell.

Adolescent↗
PubMed1985

Inhibition of leukotriene C4 and B4 generation by human eosinophils and neutrophils with the lipoxygenase pathway inhibitors U60257 and BW755C.

Human eosinophils and neutrophils have the capacity to generate leukotriene C4 (LTC4) and leukotriene B4 (LTB4) respectively when stimulated by calcium ionophore A23187. Leukotriene production by mixtures of these cell types was measured by radioimmunoassay for LTC4 and LTB4, and the specificities of the assays determined by assessing cross-reactivities with a number of other arachidonic acid metabolites. The IC50S for LTC4 and LTB4 in their respective assays were 1.76 +/- 0.04 nmol and 3.00 +/- 0.08 nmol. Cross-reactivity for anti-LTC4 was shown by leukotriene D4 (LTD4) (70%) and leukotriene E4 (LTE4) (8%), when compared to LTC4, whereas in the radioimmunoassay for LTB4, only the 5(S), 12(R) 6-trans isomer of LTB4 showed appreciable interaction (12%). LTC4 production by eosinophil enriched cell fractions obtained from metrizamide gradients was inhibited in a dose-dependent fashion by the prostacyclin analogue, 6,9-deepoxy-6,9-phenylimino-delta 6,8-prostaglandin I, (U60257) and by 3-amino-1-(3-trifluoromethyl phenyl)-2-pyrazole (BW755C). The ID50 values for U60257 and BW755C were 2 X 10(-6) and 5 X 10(-6) M respectively. This demonstration of LTC4 production by human eosinophils, which are known to be important cells in clinical asthma, provides an in vitro model to assess 5-lipoxygenase inhibitors in human tissue.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1985

Allergen-induced release of sulphidopeptide leukotrienes (SRS-A) and LTB4 in allergic rhinitis.

Leukotrienes are a recently discovered group of arachidonic acid-derived lipid mediators. Using radioimmunoassay and high pressure liquid chromatography (HPLC), we have identified the SRS-A sulphidopeptide leukotrienes (LTC4, LTD4 and LTE4) in nasal washings from patients with allergic rhinitis who underwent nasal challenge with specific allergen. Smaller, but significant, amounts of LTB4 were also detected. The concentrations of nasal leukotrienes were directly related to the dose of allergen, and were recovered in washings in a time-dependent fashion after challenge. When the patients were subjected to methacholine nasal challenge on a control day, we found only negligible amounts of either the sulphidopeptide leukotrienes or LTB4. These findings support the view that LTC4, LTD4 and LTE4 might contribute to the pathogenesis of allergic rhinitis as a result of their recognized effects on mucous hypersecretion and vasopermeability, and that the potent chemoattractant LTB4 might be involved in the subsequent infiltration of inflammatory cells.

Adult↗
PubMed1985

Mediators of hypersensitivity and "fog"-induced asthma.

Seven asthmatic and five normal subjects inhaled increasing amounts of nebulized water ("fog"). Neutrophil chemotactic activity (NCA), histamine and FEV1 measurements were undertaken before and at time intervals after challenge. In asthmatics, the mean maximal reduction in FEV1 (+/- 1 SD) was 46.6% +/- 11.5; whereas, in normal subjects, the reductions were less than 20% of pre-challenge values after the inhalation of 33 ml of water. There were no significant differences in the pre-challenge values for NCA between the asthmatics and the normal controls. When the highest values for NCA during the 30 min after challenge in the asthmatics were compared with controls there was a significant increase (P less than 0.02). The percentage change in NCA was also significantly greater in the asthmatics compared with the controls at 10 min after challenge (P less than 0.05). Fog-induced NCA was shown to be associated with proteins with approximate molecular weight of 600,000 daltons (as assessed by gel filtration chromatography on Sephacryl-S400). There was an increase in plasma histamine in the asthmatics after challenge but this was not significantly greater than the controls. These findings support the view that mediators might be involved in fog-induced asthma, possibly as a result of mast cell degranulation by "osmotic shock".

Adult↗
PubMed1985

Airways reversibility after prednisolone therapy in chronic asthma is associated with alterations in leukocyte function.

In 6 patients with chronic asthma, we studied the effects of orally administered prednisolone on monocyte and neutrophil membrane receptor expression for IgG (Fc) and complement, neutrophil locomotion, and calcium ionophore-induced leukotriene C4 production by granulocytes. Prior to treatment, monocyte IgG (Fc) and complement receptor expression, but not neutrophil IgG (Fc) or complement receptor expression, were increased when patients were compared with nonasthmatic control subjects (p less than 0.01 and p less than 0.01, respectively). After a 7-day course of orally administered prednisolone (30 mg/day daily), the increases in peak expiratory flow rate were accompanied by significant decreases from baseline in the percent of monocyte IgG (Fc) (Day 3, p less than 0.001; Day 7, p less than 0.001), monocyte complement (Day 3, p less than 0.001; Day 7, p less than 0.001), and neutrophil complement rosettes (Day 3, p less than 0.02; Day 7, p less than 0.02), but not neutrophil IgG (Fc) rosettes. Neutrophil locomotion in vitro, in response to casein, from the asthmatics was enhanced when compared with cells from control subjects, and was significantly depressed following prednisolone. Each of the 6 subjects had a peripheral blood eosinopenia in response to prednisolone that corresponded to a decrease in the amount of immunoreactive LTC4 generated from granulocyte suspensions challenged with the calcium ionophore A23187. These findings suggest that prednisolone suppresses monocyte and neutrophil activation in chronic asthma and that this is accompanied by an improvement in lung function.

Adult↗
PubMed1984

Migration of retained pacemaker electrodes.

Two cases of migration of retained pacemaker electrodes are described. The first presented as an unusual cause of deep vein thrombosis while the second was asymptomatic and detected by routine chest x-ray. Both made a good recovery, the first with surgery and the second with the fragment left in situ. A review of the world literature revealed only 13 other such cases. Of the total of 15 cases four are known to have died. In these patients no relationship was found between morbidity and the site of migration or associated infection and/or thrombosis. However surgical treatment appeared to be associated with a better prognosis.

Aged↗
PubMed1984

Immunologic studies in allergen-induced late-phase asthmatic reactions.

We have measured plasma histamine, serum neutrophil chemotactic activity (NCA) and complement (C3 and C4) over a 24-hour period in patients experiencing either early- and late-phase (dual) or single early asthmatic reactions to inhaled allergens. There was a significant biphasic elevation in plasma histamine, which paralleled the fall in forced expiratory volume in 1 sec in 10 patients with dual responses, whereas in seven subjects with single early reactions, only a single early increase in histamine concentrations was observed. In general, in the individual subjects, the changes in plasma histamine paralleled both the elevations in serum NCA and the decreases in forced expiratory volume in 1 sec. By gel filtration on Sephacryl S-400, anion exchange chromatography on DEAE Sephacel, and chromatofocusing with Polybuffer Exchanger 94, the major NCA of both the early and the late reactions was associated with proteins having an estimated molecular size of 600,000 daltons, an elution from DEAE Sephacel at 0.15M to 0.30M of NaCl (pH 8.1), and a pI of approximately 6.5. There were no appreciable changes in serum C3 and C4 up to 24 hr after challenge in subjects with late-phase responses. The patterns of asthmatic response were not related to either the total or allergen-specific serum IgE or IgG4 concentrations. These results support the view that mediators of hypersensitivity participate in late-phase as well as early asthmatic reactions.

Adolescent↗
PubMed1984

Preferential generation of leukotriene C4 by human eosinophils.

The leukotriene generating capacities of ionophore stimulated human eosinophils and neutrophils were compared using specific radioimmunoassays for LTB4 and LTC4. Mixed granulocyte preparations (neutrophils and eosinophils) produced both LTB4 and LTC4 in a time-dependent fashion which was maximal at 10 and 15 min, respectively. Following the separation of eosinophils (greater than 75%) and neutrophils (greater than 90%) by metrizamide gradients, LTC4 production was predominantly from eosinophils, whereas neutrophils were the principal source of LTB4. The concentrations of leukotrienes produced by the eosinophil and neutrophil rich cell preparations were directly proportional to the concentration of ionophore. Following purification of eosinophil derived products by RP-HPLC the LTC4 immunoreactivity corresponded to the elution profile of a synthetic LTC4 marker. Furthermore, in 32 atopic subjects (21 bronchial asthmatics and 11 non-asthmatics) the amounts of LTC4 produced by unseparated leucocytes were directly proportional to the percentage of eosinophils in the total cell suspension. Preferential generation of LTB4 by neutrophils was also demonstrated by immunoreactivity of ionophore stimulated supernatants subjected to RP-HPLC, as well as by its characteristic u.v. absorbance and GC-MS profile and the ability to promote directional neutrophil locomotion (chemotaxis). These experiments support the concept that eosinophils accumulate in tissues partly as a result of the response to neutrophil derived LTB4, and that these cells contribute to the production of sulphidopeptide leukotrienes with subsequent amplification of the acute allergic response.

Adolescent↗
PubMed1982

Do oral and inhaled terbutaline have different effects on the lung?

The effect of inhaled or oral terbutaline on the subsequent response to inhaled terbutaline was studied using a double-blind cross-over technique in 12 asthmatic patients. 12 indices of respiratory function were obtained from the maximal flow-volume loop and a single-breath inert gas technique. These were used to evaluate the effect and to attempt to distinguish the site of action of the drug. Although the initial dose of inhaled terbutaline had a greater immediate effect than its oral counterpart there were no significant differences in the response to subsequently inhaled terbutaline. These findings do not support recent suggestions that oral administration has a greater effect on distal airways or promotes the effects of inhaled bronchodilators.

Administration, Oral↗
PubMedDate not supplied

Temperament in juvenile eating disorders.

Previous studies have suggested an association between temperament and eating disorder pathology. The purpose of this study was to differentiate on the basis of temperament among patients with anorexia, bulimia, and major depression. In this study, 101 adolescent girls completed the Revised Dimensions of Temperament Survey (Self), a self-report measure that identifies nine dimensions of temperament. Significant differences were found between the diagnostic groups while controlling for disturbances in mood and defensiveness. Specific subscales differentiated the subjects with anorexia from those with bulimia. These data support the concept of using temperament to differentiate patients with related psychiatric syndromes.

Adolescent↗
PubMedDate not supplied

Bulimia as a disturbance of narcissism: self-esteem and the capacity to self-soothe.

A review of the literature on eating disorders reveals that, although psychodynamic formulations linking narcissistic dynamics--particularly difficulties with self-soothing--and eating disorders are common in the theoretical and clinical literature, little empirical work has attempted to substantiate this claim. In this study, 117 women completed the Eating Disorder Inventory and the Bulimia Test Revised and four scales that measure different components of narcissism (the Multidimensional Self-Esteem Inventory, measuring self-esteem, the Self-Care Questionnaire, and two subscales of the Ego Functioning Assessment Questionnaire, measuring self-soothing). The four scales used to assess narcissism were all highly correlated with each other, indicating that they measure a similar construct. In addition, the eating-disorder measures were correlated with the measures of narcissism, suggesting that a relationship exists between bulimia and narcissism, as assessed using self-report instruments.

Adolescent↗
PubMedDate not supplied

Activated human eosinophils generate SRS-A leukotrienes following IgG-dependent stimulation.

Eosinophils, a class of granular leukocytes, are prominent in many inflammatory processes, particularly in asthma, certain allergic diseases and during infections with helminthic parasites. Following incubation with the Ca ionophore A23187 (refs 1-4) (a non-physiological agent which circumvents membrane calcium-gating mechanisms), eosinophils generate large amounts of sulphidopeptide leukotrienes, potent inducers of smooth muscle constriction and mucus production. These are now known to represent the activity previously termed 'slow-reacting substance of anaphylaxis' (SRS-A) but attempts to identify a physiological stimulus for SRS-A production by eosinophils have so far been unsuccessful. The cells contain recognized receptors for IgG (Fc) and it is known that they adhere to, and can be activated by, contact with the surface of large organisms such as helminthic larvae. We show here that eosinophils, particularly when activated, produce sulphidopeptide leukotrienes after contact with large particles coated with IgG.

Eosinophilia↗
PubMedDate not supplied

Age differences in components of metamemory.

Young adults (N = 58) and older adults (N = 55) answered 30 questions extracted from three dimensions of the Metamemory in Adulthood (MIA) questionnaire: Capacity, Task and Strategy. The older participants scored significantly lower on the Capacity dimension, indicating that they report having greater difficulty in everyday memory situations. There was no age difference on any item in the Task dimension; both groups were equally knowledgeable about memory task demands. Responses to Strategy items varied with type of strategy: younger adults were more likely than older adults to report the use of encoding strategies, while older adults reported significantly more use of strategies which involved planning and organization. A further group of employed young adults (N = 26) was added to clarify the respective roles of aging and environmental demands on strategy use. The findings suggest that both changes in lifestyle and the effects of aging per se play some part in the use of particular memory strategies.

Adolescent↗