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R J Shaw

Publications and source records attributed to R J Shaw.

At least 127 records · Page 7Linked to original sources
PubMed1992

Modulation of platelet-derived growth factor B mRNA abundance in macrophages by colchicine and dibutyryl-cAMP.

Macrophage production of growth factors for fibroblasts, in particular platelet-derived growth factor B [PDGF(B)] and transforming growth factor-beta (TGF-beta), is thought to be central to the pathogenesis of pulmonary fibrosis. In a search for anti-inflammatory agents that might prevent this process, we asked whether colchicine might modulate the abundance of PDGF(B) and TGF-beta mRNA, as well as the mRNA of early growth response gene 2 (EGR2), in human macrophages. Colchicine caused a dose- and time-dependent increase in PDGF(B), but not TGF-beta or EGR2, mRNA in human macrophages derived from culture of peripheral blood monocytes. Similarly, colchicine caused an increase in PDGF(B) mRNA in human alveolar macrophages obtained from normal volunteers. Colchicine also caused an increase in PDGF(B) protein production by macrophages, as determined by enzyme-linked immunosorbent assay. Interferon-gamma further increased the PDGF(B) mRNA abundance in human alveolar but not monocyte-derived macrophages. The effect of coincubation with dibutyryl-cAMP (dBcAMP) was assessed in an attempt to prevent the colchicine-induced increase in PDGF(B) mRNA. dBcAMP alone resulted in no increase in PDGF(B) mRNA or alteration in TGF-beta mRNA but resulted in a reduction in EGR2 mRNA. When added with colchicine, dBcAMP completely abrogated the colchicine-induced increase in PDGF(B) mRNA but had little effect on TGF-beta mRNA. These data, showing that colchicine increased macrophage PDGF(B) mRNA in human macrophages and that this was prevented by coincubation with dBcAMP, lead us to speculate that colchicine may not be helpful in preventing the contribution of macrophage PDGF(B) gene activation to the pathogenesis of lung fibrosis. However, this effect of colchicine may be prevented by increasing intracellular cAMP in macrophages.

Bucladesine↗
PubMed1991

Effects of adult age on structural and operational capacities in working memory.

Eight experiments were conducted in which young adults and older adults were asked to report the latest value of 1 of several continuously changing numeric or spatial variables. Accuracy of reporting the current value of the target variable was lower with increases in the number of potentially relevant variables and with increases in the number of required processing operations. Young and older adults exhibited similar effects of the number of potentially relevant variables (hypothesized to be sensitive to the structural capacity of working memory) and of the number of required processing operations (hypothesized to be sensitive to the operational capacity of working memory), but older adults were generally less accurate than young adults.

Adult↗
PubMed1991

Age-related increases in the effects of automatic semantic activation.

Automatic semantic activation was assessed in a version of the flanker task, in which nominally irrelevant words were presented above and below a target word. The category membership of the flanking word was consistent, inconsistent, or neutral with respect to the target word. Older adults showed greater inhibition and equivalent facilitation in the time taken to classify the target words than did younger adults in 2 of 3 experiments, in contrast to previous findings. The present results are generally consistent with 3 dominant perspectives in cognitive aging: the complexity hypothesis, environmental support, and the inhibition-deficit view. Manipulation of the overall magnitude of the flanker effect produced results most consistent with the inhibition-deficit view that older adults are less able to inhibit automatic processes than are younger adults. Some problems with the inhibition-deficit view are also discussed.

Adolescent↗
PubMed1991

Pathogenesis of pulmonary fibrosis in interstitial lung disease. Alveolar macrophage PDGF(B) gene activation and up-regulation by interferon gamma.

Alveolar macrophages are believed to be central in orchestrating the fibrotic response in interstitial lung disease (ILD). To test the hypothesis that macrophages from patients with ILD were dedicated to growth factor production and that this was independent of other indices of macrophage activation, we measured the mRNA of the B chain of PDGF and TGF-beta, as well as HLA-DR-alpha in alveolar macrophages from patients with ILD and from normal control subjects. When alveolar macrophages were examined immediately after lavage, cells from patients with ILD had increased PDGF(B) but similar TGF-beta and HLA-DR-alpha mRNA when compared with control subjects. Discoordinate regulation of these genes was observed when alveolar macrophage PDGF(B) mRNA increased while TGF-beta and HLA-DR-alpha mRNA decreased after culture for 24 h. This response was not disease-related as these changes were similar in cells from patients with ILD and from control subjects. Because a lymphocytic alveolitis is present in many cases of ILD, we asked whether interferon gamma (IFN-gamma) modulated the activation of these genes. In both the patients and the control subjects, PDGF(B) and HLA-DR-alpha, but not TGF-beta, mRNA were increased after incubation with IFN-gamma. These results indicate that PDGF(B) mRNA may be increased in alveolar macrophages in ILD and that PDGF(B), TGF-beta, and HLA-DR-alpha are independently regulated genes in alveolar macrophages, but that IFN-gamma increases both PDGF(B) and HLA-DR-alpha mRNA. We speculate that IFN-gamma induced PDGF(B) gene activation may be an important mechanism by which lymphocytes promote pulmonary fibrosis.

Adult↗
PubMed1990

Adherence-dependent increase in human monocyte PDGF(B) mRNA is associated with increases in c-fos, c-jun, and EGR2 mRNA.

Adherence is an important initial step in the transition of a circulating monocyte to a tissue macrophage. This differentiation is accompanied by an augmented capacity to generate growth factors. We hypothesized that adherence itself might be an important trigger for a sequence of gene activation culminating in cells with increased mRNA encoding profibrotic growth factors such as platelet-derived growth factor B subunit (PDGF[B]) and transforming growth factor-beta (TGF-beta). After in vitro adherence, human monocytes had a biphasic increase in PDGF(B) mRNA with peaks at 6 h and 13 d. No increase in TGF-beta mRNA was observed. The 6-h increase in PDGF(B) mRNA was adherence dependent, and in addition, was abrogated when the cytoskeletal integrity was compromised by cytochalasin D. The 6-h increase in PDGF(B) mRNA was unaltered by adherence in the presence of the monocyte stimulus lipopolysaccharide. Adherence to either fibronectin or collagen-coated plastic had little consistent effect on PDGF(B) mRNA accumulation. The increased PDGF(B) mRNA observed in adherent monocytes was accompanied by increases in mRNAs of the early growth response genes c-fos (maximal at 20 min), c-jun, and EGR2 (maximal at 6-24 h). The increase in c-jun and EGR2, but not c-fos, mRNA was also abrogated by cytochalasin D. These observations suggest that adherence results in increases of c-fos, c-jun, EGR2, and PDGF(B) mRNA. In addition, the increases in c-jun, EGR2, and PDGF(B) may depend on cytoskeletal rearrangement. Modulation of these events at the time of adherence offers a mechanism by which differential priming of the cells may be accomplished.

Cell Adhesion↗
PubMed1989

Myoclonus associated with treatment with high doses of morphine: the role of supplemental drugs.

OBJECTIVE: To estimate the prevalence of important side effects in patients with malignant disease who were receiving high doses of morphine as part of their palliative treatment. DESIGN: Data on patients were collected over 12 months. SETTING: Two palliative care units in Western Australia. PATIENTS: 19 Patients with malignant disease who were receiving morphine either subcutaneously or orally as the main analgesic. 10 Patients receiving a total daily dose of morphine of at least 500 mg orally or 250 mg parenterally were enrolled in the study. The other 9 patients were enrolled after an important problem thought to be related to the morphine had been identified. All of the patients were taking drugs to supplement the treatment. INTERVENTIONS: The dose of morphine or route of administration, or both, was changed in three patients. MAIN OUTCOME MEASURE: Determination of the prevalence of side effects in the patients. Assessment of the relation of any side effects with the supplemental drugs taken by the patients. MAIN RESULTS: Plasma morphine and electrolyte concentrations were measured and a full history taken for each patient. Thirteen of the 19 patients had an important side effect; 12 of them had myoclonus and one had hyperalgesia of the skin. Plasma morphine concentrations were similar in patients with and without myoclonus, ranging from 158 to 3465 nmol/l and 39 to 2821 nmol/l respectively. Eight of the patients with side effects were taking an antipsychotic drug concurrently compared with none of those without side effects. A greater proportion of patients with side effects were taking the antinauseant drug thiethylperazine (6/13 v 2/6) and at least one non-steroidal anti-inflammatory drug (10/13 v 2/6), whereas a smaller proportion were taking a glucocorticosteroid (3/13 v 4/6). The estimated prevalence of important side effects in the total population of patients receiving palliative treatment in the two units was 2.7-3.6%. CONCLUSIONS: Myoclonus as a side effect of treatment with morphine is more likely to occur in patients taking antidepressant or antipsychotic drugs as antiemetics or as adjuvant agents or non-steroidal anti-inflammatory drugs for additional analgesia. If a patient develops myoclonus the best approach may be to change the supplemental treatment.

Adult↗
PubMed1989

Echinococcus granulosus: ultrastructure of epithelial changes during the first 8 days of metacestode development in vitro.

The epithelium of artificially hatched and activated oncospheres of E. granulosus was studied ultrastructurally over the first 8 days of metacestode development in vitro. Within 4 h of activation, the epithelium was transformed from a thin cytoplasmic layer into a much wider layer packed with penetration gland granules and containing mitochondria and Golgi apparatus. Microvilli were extended from the outer plasma membrane and the basal lamina on the inner epithelial surface virtually disappeared. Microvilli increased in number and length over the first 24 h of development while granules in both the epithelium and penetration gland decreased in number. The granules appear to be involved in microvilli formation. After 3 days of development, the first lamination resolved ultrastructurally as shortened microvilli and some microtriches extending from the epithelium surrounded by an electron-dense microfibrillate material containing sloughed microvilli. By 6 days post-activation, no microvilli remained and only double-walled truncated microtriches extended from the epithelium. The microfibrillate material had become more electron-dense and was closer to the epithelium than at day 1. Within 8 days of metacestode development, a second lamination had developed. Both microfibrillate and particulate material of a greater electron density than the first lamination was added to the microthrix side of the first lamination.

Animals↗
PubMed1989

Age differences in predictions and performance on a cued recall task.

The notion that older adults fail to use optimal encoding strategies in memory tasks because of a deficit in memory monitoring was examined in a cued recall task. Participants were given different types of descriptors (initial letters, rhyme, category) for each word during encoding, and these descriptors were later given as cues at recall. Participants also predicted the likelihood of recalling each item. Age differences were found in recall performance, but there were no age differences in average predictions. However, the prediction ratings given by younger adults showed a greater difference between words recalled and words not recalled in the subsequent test than did the ratings of the older adults. Differences in recall associated with different types of processing were predicted poorly by all of the participants, but the relative recallability of specific words was well assessed by both age groups. We concluded that a memory monitoring deficit is not likely to be responsible for age differences in memory.

Adult↗
PubMed1988

Leukotriene C4 generation from human eosinophils stimulated with IgG-Aspergillus fumigatus antigen immune complexes.

Sepharose beads coated with IgG stimulate eosinophils to produce leukotriene C4 (LTC4). This observation has been extended with specific immobilized IgG/antigen immune complexes to elicit mediator generation. An extract of Aspergillus fumigatus was covalently coupled to Sepharose beads and incubated with the IgG fraction of immune serum from patients with allergic bronchopulmonary aspergillosis. These beads elicited generation of 7.72 +/- 1.7 pmol of LTC4 immunoreactive material (n = 5) from 1 X 10(6) normal eosinophils of greater than 86% purity, and significantly less LTC4 (0.73 +/- 0.19 pmol per 10(6) cells; n = 3) was produced by eosinophils after incubation with beads treated with IgG from normal nonimmune serum. The maximum antibody-dependent release achieved represented approximately 20% of that induced by the calcium ionophore (A23187). LTC4 was measured by radioimmunoassay and validated by reverse-phase high-performance liquid chromatography. The amount of LTC4 generated was dependent on the concentration of A. fumigatus-specific IgG, and mediator release was completely abolished by prior adsorption of the IgG fraction onto Sepharose-protein A (Staphylococcus aureus). Grass pollen-specific IgG antibody/antigen complexes, in combination with Sepharose beads, also triggered generation of LTC4 immunoreactive material. There was no evidence to suggest that IgE/A. fumigatus immune complexes triggered LTC4 generation, although IgE myeloma protein, in association with Sepharose beads, was a weak stimulus. The efficacy of the IgG immune complex-dependent stimulation of eosinophils suggests a possible physiologic mechanism whereby these cells could participate in the inflammatory changes associated with allergic bronchopulmonary aspergillosis and similar allergic disorders.

Antigen-Antibody Complex↗
PubMed1988

Influence of atopy on the clinical manifestations of coronavirus infection in adult volunteers.

In an attempt to understand the relationship between viral upper respiratory tract infection and the underlying virological and immunological mechanisms, thirty-four volunteers were inoculated intranasally with coronavirus 229E; subsequent virus shedding and/or antibody rises, indicating active infection, were observed in twenty-nine. There was a greater increase in independently measured scores of clinical severity, e.g. cold symptoms, in those with detectable IgE in nasal secretions (P less than 0.01). A similar association was found between clinical scores and serum IgE concentrations greater than or equal to 150 IU/ml, but the relationship with systemic atopy, as assessed by skin-prick tests to common allergens, was less marked. A more detailed study of twelve of the infected volunteers failed to explain these findings on the basis of mast cell mediator release, as concentrations of leukotriene B4, the sulphidopeptide leukotriene C4, and histamine, were not appreciably elevated in the nasal secretions following virus inoculation. Similarly, there was no evidence that circulating coronavirus specific IgE was produced. Thus, this study suggest that atopy may be related to the severity of cold symptoms produced by coronavirus 229E, although the exact connection has yet to be determined.

Adolescent↗
PubMed1988

Lung function abnormalities in patients infected with the human immunodeficiency virus with and without overt pneumonitis.

Pulmonary function was measured in 169 male patients seropositive for the human immunodeficiency virus (HIV). The transfer factor for carbon monoxide (TLCO) in symptom free patients and patients with persistent generalised lymphadenopathy was normal (greater than 83% of predicted values). Patients with the AIDS related complex, non-pulmonary Kaposi sarcoma, and non-pulmonary non-Kaposi sarcoma AIDS (that is, opportunist infections affecting other organs) had lower mean values for TLCO (77%, 70%, and 70% of predicted respectively). These values were significantly lower than values for symptom free patients. Lower mean values of 50% and 63% predicted TLCO were observed in patients during the acute and recovery phases of Pneumocystis carinii pneumonia. TLCO was also low in patients with lung mycobacterial infection and in a patient with lung Kaposi sarcoma. Forced expiratory volume in one second, peak expiratory flow, and maximal expiratory flow at 50% of vital capacity were significantly reduced only in patients with acute pneumocystis pneumonia. This study shows that abnormalities in the results of pulmonary function tests, particularly TLCO, although greatest in patients with pulmonary complications of AIDS, are also present in patients with AIDS but without other evidence of pulmonary disease, and in patients with the AIDS related complex. The predictive and prognostic implications of these findings require further investigation.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Diagnostic specificity of a sandwich ELISA for Aspergillus-related diseases.

A sandwich ELISA with specificity for a major antigen (Ag 7) of Aspergillus fumigatus has been compared with indirect ELISAs with use of crude antigenic (culture filtrate) extracts and found to have a sensitivity of 100% and specificity of 92.3% for antibody detection in sera of patients with allergic bronchopulmonary aspergillosis (ABPA) and aspergilloma. In the Ag 7 ELISA, all sera from groups with ABPA (21) and aspergilloma (15) had positive titers, and mean values for both these groups were significantly higher (p less than 0.001) than control levels. By comparison, in the indirect ELISAs, most sera of patients with ABPA were positive; the sensitivity was 81% to 90%, and the specificity was 87%. Sera from other disease groups including sera from 13 patients with farmer's lung, 16 with tuberculosis, and 10 individuals with positive prick test to either A. fumigatus or Alternaria alternata were also tested by both types of assay. Up to five of these sera elicited significant positive results in the indirect ELISA, and although two sera were also positive in the Ag 7-specific ELISA, these latter titers were both below the range of values for the sera from patients with ABPA. With the use of an IgG calibration curve, the sensitivity of the assay was determined as within the range of 1 to 10 microgram of specific IgG antibody per milliliter. The Ag 7-specific ELISA is therefore a highly specific, sensitive assay for antibody detection in Aspergillus-related diseases.

Antibodies, Fungal↗
PubMed1986

Enteral and systemic release of leukotrienes during anaphylaxis of Nippostrongylus brasiliensis-primed rats.

Rats with acquired immunity to the intestinal nematode Nippostrongylus brasiliensis develop anaphylaxis after i.v. challenge with an extract of worm antigen, with the small intestine being the primary shock organ. In the present study we have shown that these events were associated with significant elevations in intestinal and plasma concentrations of leukotrienes LTB4 and LTC4. The changes were observed in immune rats over 10-, 30-, and 60-min intervals after antigen challenge but were absent in control animals. These lipid mediators were identified both in the perfusate of the gut lumen, which contained large quantities of mucus, and in homogenates of intestinal tissue. In addition, significant elevations in the concentrations of plasma LTB4 and LTC4 were detected in immune challenged rats but not in controls. Leukotrienes were identified by radioimmunoassay and validated by reverse-phase high-performance liquid chromatography (RP-HPLC). RP-HPLC analysis of SRS-A leukotrienes in immune challenged rats indicated that LTC4 was the predominant sulfidopeptide leukotriene at 10 min, with almost complete biodegradation to LTD4 and LTE4 within 30 min. Infected rats also had significant increases in the numbers of intestinal mucosal mast cells (MMC) and eosinophils. Evidence of MMC activation during anaphylaxis was obtained by showing significant elevations of intestinal and systemic concentrations of their exclusive serine enzyme, rat mast cell proteinase II (RMCPII). Thus, the release of substantial amounts of leukotrienes in the gut and plasma of N. brasiliensis-primed rats after interaction with worm antigens suggests that these potent mediators may play an important role in allergic-type hypersensitivity known to occur during immune reactions against parasitic helminths.

Anaphylaxis↗
PubMed1986

Aging and the time course of semantic activation.

Fifty-four young (M age = 20.2 years) and 54 elderly participants (M age = 68.4 years) completed a task in which a prime was followed by a target. People were to respond "yes" if the target was a word and "no" otherwise. On word-target trials, three kinds of prime were presented: associated (e.g., the prime-target pair DOG-CAT), unassociated (e.g., SEW-CAT), and neutral (e.g., BLANK-CAT). The stimulus onset asynchrony (SOA) between onset of the prime and target was varied, with SOAs of 150, 450, and 1,000 ms. The most important finding was an age difference in the minimum SOA at which priming (i.e., faster response time on associated than on unassociated trials) was observed. It is argued that the age difference in onset of priming reflects a slowing with age in one or more aspects of semantic activation. Contrary to the Hasher and Zacks (1979) hypothesis, there is evidence of an age difference in the speed of automatic activation.

Adult↗
PubMed1986

Enhancement of leukocyte cytotoxicity after exercise-induced asthma.

We have previously shown that there were elevations of neutrophil chemotactic activity (NCA) and increases in the percentages of neutrophil and monocyte complement rosettes after exercise-induced asthma (EIA). These observations suggested that leukocyte activation may occur after EIA, possibly as a result of the release of mast-cell-associated mediators. In the present study, we have attempted to establish whether neutrophils and monocytes are functionally altered after EIA as assessed by changes in their cytotoxic capacity. Cytotoxicity was assessed by a direct visual killing assay using opsonized (complement-coated) schistosomula of Schistosoma mansoni as target organisms. Neutrophils and mononuclear cells obtained from 8 patients after exercise-induced asthma (EIA+ve) had increased cytotoxicity for opsonized schistosomula for as long as 60 min after exercise. These changes were preceded by elevations in the concentrations of serum high molecular weight NCA (which were maximal at 10 min after exercise). In asthmatic patients who did not develop exercise-induced asthma (EIA-ve), no significant increases in neutrophil or mononuclear cell killing of schistosomula, or serum NCA concentrations, were observed. There was a highly significant correlation (p less than 0.001) between the reduction in FEV1 and the increases in neutrophil cytotoxicity. In 5 EIA+ve patients, administration of disodium cromoglycate (cromolyn) prior to the exercise task inhibited both the enhancement in neutrophil and mononuclear cell cytotoxicity, as well as the elevations in circulating NCA and the reductions in FEV1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗