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Biomedical subjects

C McSharry

Publications and source records attributed to C McSharry.

At least 55 records · Page 3Linked to original sources
PubMed1992

Characterization of IgE antibody binding profiles of sera from patients with atopic dermatitis to allergens of the domestic mites Dermatophagoides pteronyssinus and Euroglyphus maynei, using enhanced chemiluminescent immunoblotting.

A rapid, sensitive, chemiluminescent immunoblotting method was used to identify IgE-binding components of Dermatophagoides pteronyssinus and Euroglyphus maynei that were recognized by sera of 16 D. pteronyssinus-sensitive patients with atopic dermatitis. Some 28 components (14-200 kD) were found in the D. pteronyssinus extract, and sera bound between 1 and 13 of them (mean 6.0). At least one of four components (97, 28, 24 and 14 kD) were bound by 14/16 sera. E. maynei had 25 components (14-227 kD), 13 in common with those of D. pteronyssinus by molecular size. Sera bound between 1 and 11 of them (mean 5.2) and 14/16 sera bound 1 of 38 kD (unique to E. maynei) and/or 1 of 175 kD. There were positive correlations between the number of D. pteronyssinus and E. maynei components bound and anti-D. pteronyssinus and E. maynei serum IgE values (p less than 0.001 in both cases) and between the number of D. pteronyssinus and E. maynei components bound and total serum IgE values (p less than 0.01 in both cases). These results demonstrate a very considerable diversity of IgE antibody responses to domestic mite allergens amongst patients with atopic dermatitis.

Adult↗
PubMed1991

The distribution of alternative agents for targeted radiotherapy within human neuroblastoma spheroids.

This study aims to select the radiopharmaceutical vehicle for targeted radiotherapy of neuroblastoma which is most likely to penetrate readily the centre of micrometastases in vivo. The human neuroblastoma cell line NB1-G, grown as multicellular spheroids, provided an in vitro model for micrometastases. The radiopharmaceuticals studied were the catecholamine analogue metaiodobenzyl guanidine (mIBG), a specific neuroectodermal monoclonal antibody (UJ13A) and beta nerve growth factor (beta NGF). Following incubation of each drug with neuroblastoma spheroids, autoradiographs of frozen sections were prepared to demonstrate their relative distributions. mIBG and beta NGF were found to penetrate the centre of spheroids readily although the concentration of mIBG greatly exceeded that of beta NGF. In contrast, UJ13A was only bound peripherally. We conclude that mIBG is the best available vehicle for targeted radiotherapy of neuroblastoma cells with active uptake mechanisms for catecholamines. It is suggested that radionuclides with a shorter range of emissions than 131I may be conjugated to benzyl guanidine to constitute more effective targeting agents with potentially less toxicity to adjacent normal tissues.

3-Iodobenzylguanidine↗
PubMed1991

Quantifying serum antibody class and subclass responses by enzyme immunoassay in humidifier-related disease.

Antibody activity in the major classes and IgG subclasses against antigens in factory humidifier water was quantified by enzyme immunoassay (EIA) in 88 subjects who were exposed at work to the output from these contaminated humidifiers. Those with work-related symptoms had significantly higher mean titres than those who were symptom free, although values overlapped. The individuals with the highest IgG antibody titres also had the highest titres of IgM and IgA antibody, and these parameters did not discriminate between those with and without symptoms any better than the IgG titre. This was also true for the IgG subclasses where activity was predominantly measured in IgG1. Quantifying the IgG antibody allowed us to demonstrate a significant correlation with years of work exposure (P less than 0.001). There was no significant association between antibody and cigarette smoking, as assessed by smoking history and confirmed objectively by serum cotinine levels. There was a significant correlation with total IgG level (P less than 0.001) suggesting that a non-specific immune enhancement may accompany the specific response. The antibody titres were followed up to 3 years after modification of the humidification systems, and during this time symptoms resolved and the antibody levels progressively fell to undetectable levels. The EIA was adapted to measure antigen at nanogram levels thus providing a rapid test for screening of humidifer water as well as a technique that may help identify the nature of the antigens involved.

Air Conditioning↗
PubMed1990

The role of mast cell degranulation products in mast cell hyperplasia. I. Mechanism of action of nerve growth factor.

A variety of mast cell degranulating agents have previously been shown to induce mast cell hyperplasia in adult rats. In neonates 2.5 S nerve growth factor (NGF) induces a hyperplasia of both mucosal and connective tissue mast cells (MMC and CTMC). We have examined the role of the potent mast cell degranulating properties of NGF on its ability to induce mast cell hyperplasia. Administration of NGF in combination with the mast cell stabilizing agent disodium cromoglycate was found to abrogate the CTMC hyperplasia induced by NGF alone. Treatment of neonatal rats with the alternate degranulating agent compound 48/80 was found to induce a limited CTMC but not a MMC hyperplasia. A supernatant obtained by degranulating purified adult rat peritoneal mast cells with anti-IgE was found to induce hyperplasia of the CTMC population similar to that observed with NGF administration. However, this degranulation product supernatant only induced a limited MMC hyperplasia as judged by RMCP II content of the tissues. These results suggest that NGF has dual action inducing mast cell hyperplasia; CTMC hyperplasia being dependent on the ability of NGF to degranulate mast cells. MMC hyperplasia induced by NGF is independent of CTMC degranulation. Degranulation products from peritoneal mast cells act to increase both MMC and CTMC populations in the neonate. These data suggest that the CTMC population may be regulated by an autocrine positive feedback mechanism in vivo.

Animals↗
PubMed1989

Pulmonary abnormalities in Crohn's disease.

Abnormalities of pulmonary function in Crohn's disease have been described, although the results are conflicting and anecdotal accounts of lung involvement are few. In this study we assessed the prevalence of lung function abnormalities in Crohn's disease, and the relative contributions of age, sex, smoking and past medical history, and Crohn's disease activity to the pulmonary abnormalities found. Twenty-nine patients with Crohn's disease and 29 age-, sex- and smoking-matched volunteer controls underwent detailed respiratory assessment. Airways obstruction due to chronic bronchitis and asthma was present in 13 patients with Crohn's disease, but was not more prevalent than in the control group. FEV1 was similar in both Crohn's disease and control subjects (84.2 +/- 21.2% predicted, mean +/- SD; 93.7 +/- 16.3%, respectively: n.s.). The vital capacity was significantly lower in the Crohn's disease patients than in controls (86.7 +/- 16.6%; 95.9 +/- 12.7%; P less than 0.01), but this may have been influenced by the higher prevalence of past or intercurrent medical illnesses affecting the chest in Crohn's disease patients. No patient had evidence of fibrosing alveolitis or bronchiectasis. The haemoglobin corrected transfer factor was significantly lower in the Crohn's disease patients than in controls (100.4 +/- 17.4%; 113.2 +/- 25.1: P less than 0.05) but the diffusing coefficient was not significantly different. There was a significant correlation (r = 0.44, P less than 0.05) between the residual volume and the Crohn's disease activity index but otherwise no close relationship was observed between Crohn's disease activity, extent or duration and the indices of lung function. These findings suggest that the lungs are relatively unaffected by Crohn's disease.

Adult↗
PubMed1989

A controlled trial of house dust mite eradication using natamycin in homes of patients with atopic dermatitis: effect on clinical status and mite populations.

In a controlled clinical trial, patients with atopic dermatitis carried out house dust mite eradication procedures on their mattresses, using natamycin or a matched placebo spray, with or without vacuum cleaning, for 4 months. For the two groups that used vacuum cleaning, mite numbers fell significantly both by comparison of mean initial and final numbers and by calculating mean rates of reduction from regression analyses (P less than 0.01 in all cases). There were no differences between the groups in the magnitude of the decreases. For the two groups that did not use vacuum cleaning, mite populations remained virtually unchanged. These results indicate vacuum cleaning not natamycin had the major effect on mite eradication. Mean symptom scores of patients in all four groups were slightly reduced by the end of the trial, but there was a greater reduction rate (P less than 0.01) in the combined scores of the groups that did not use vacuum cleaning, demonstrating a lack of correlation between improvement in clinical score and lowered mite numbers. No patients entered remission and the maximum improvement in clinical score was only 47%. Natamycin and vacuum cleaning neither alone nor in combination proved valuable in reducing mite numbers sufficiently to provide clinical benefit.

Adolescent↗
PubMed1988

Effect of house dust mite avoidance measures on adult atopic asthma.

Twenty one adult patients with asthma, with positive skin test responses to the European house dust mite, Dermatophagoides pteronyssinus, were randomly allocated to a control group or to a group applying house dust mite avoidance measures. These included an initial application of liquid nitrogen to mattresses and bedroom carpets to kill the live house dust mite population. Histamine airway responsiveness, symptom scores, peak expiratory flow rates (PEF), and house dust mite numbers were determined during the two week pretrial and eight week trial periods. Nine patients in each group completed the study. By the end of the study there was a significant reduction in live mites in the "avoidance" group but not in the control group. The avoidance group showed a significant improvement in symptom scores measured on a linear analogue scale, in the number of hours each day spent wheezing (mean reduced from 8.6 to 4.5 hours), and in PEF (l/min) both in the morning (from 364 to 388) and in the evening (from 368 to 392). These changes were not found in the control group. The provocative concentration (PC) of histamine causing a 20% fall in FEV1 (PC20FEV1) had increased significantly in the avoidance group at eight weeks (from 0.58 to 2.3 mg/ml), whereas no change was seen in the control group (from 0.93 to 1.21 mg/ml). These results show that house dust mite avoidance, combined with initial killing of the mite by liquid nitrogen, diminishes airway responsiveness and improves asthma symptom control over an eight week period in adult asthmatic patients with house dust mite allergy.

Adolescent↗
PubMed1988

Heterogeneous proliferative characteristics of human adult lung fibroblast lines and clonally derived fibroblasts from control and fibrotic tissue.

Pulmonary fibrosis results from an altered deposition of collagen within the lung parenchyma. This alteration is likely the result of both increased fibroblast proliferation and abnormalities in fibroblast collagen metabolism. Although the development of pulmonary fibrosis is preceded by inflammatory events in the lung, it is unclear whether altered fibroblast behavior requires continuous exposure to inflammatory mediators or alternatively results from the emergence in the lung of fibroblast populations possessing characteristics such as to explain the abnormalities seen in pulmonary fibrosis. To examine the latter hypothesis, we have established a number of fibroblast cell lines from control (C) lung tissue as well as from tissue from patients with active pulmonary fibrosis (PF), and have examined their in vitro proliferative characteristics. Our data show that PF fibroblasts proliferate significantly faster compared to C fibroblasts under standard culture conditions. We have also examined the in vitro proliferative characteristics of a substantial number of clonally derived fibroblasts. We report that a marked heterogeneity exists in terms of proliferation and also that a small but significant number of fast-growing clones are present in panels of clones derived from fibrotic tissue. These data suggest that there exists in fibrotic tissue, clones of fibroblasts with intrinsic growth characteristics which could in itself explain the increased fibroblast proliferation seen in pulmonary fibrosis. The fibrotic clones may emerge as dominant in the fibrotic lung under conditions of injury and repair likely to favor the expansion of this phenotype.

Adult↗
PubMed1987

Serum IgG and IgE antibody against aerosolised antigens from Nephrops norvegicus among seafood process workers.

Employees in a seafood factory developed high titers of serum IgE and IgG antibody to antigens from prawn (N. norvegicus) which were aerosolized during processing. Significant serum IgE antibody titers occurred only among those subjects with occupation-related respiratory symptoms, and this serological parameter may be a useful clinical adjunct in the investigation of this disease. Serum IgG antibody was detected with equal frequency and titer in symptomatic and asymptomatic workers. There was no significant correlation between either antibody class response and the individual's age or years of work exposure. Cigarette smoking, however, was positively associated with the IgE antibody response, and negatively associated with the IgG antibody response to the same inhaled antigen. Investigating the effects of smoking at the mucosal level in the lung may provide insight into how the lung processes and responds to inhaled antigens.

Aerosols↗
PubMed1987

Serological and clinical investigation of humidifier fever.

A group of nineteen normally healthy subjects in a microprocessor factory reported various degrees of work-related respiratory and systemic symptoms that in some were suggestive of humidifier fever (HF). They all had normal serology against a variety of infectious agents, but serum-precipitating antibody against antigens in the factory humidifier water was present in twelve subjects, primarily those with symptoms most in keeping with HF. There was extensive serological identity between the antigens from this and other confirmed sources of HF. The antibody-positive subjects were all non-smokers and had significantly raised serum IgG. Nine months later, following modification of the humidifier system, the symptoms had resolved in fourteen of the nineteen subjects, the precipitins were reduced in seven but persisted in five subjects, and the total IgG levels were significantly reduced in all subjects. The measurement of total, as well as specific, IgG may be of value in assessing this disease.

Adult↗
PubMed1986

Is homoeopathy a placebo response? Controlled trial of homoeopathic potency, with pollen in hayfever as model.

The hypothesis that homoeopathic potencies are placebos was tested in a randomised, double-blind, placebo-controlled trial. The study model chosen compared the effects of a homoeopathic preparation of mixed grass pollens with placebo in 144 patients with active hayfever. The homoeopathically treated patients showed a significant reduction in patient and doctor assessed symptom scores. The significance of this response was increased when results were corrected for pollen count and the response was associated with a halving of the need for antihistamines. An initial aggravation of symptoms was noted more often in patients receiving the potency and was followed by an improvement in that group. No evidence emerged to support the idea that placebo action fully explains the clinical responses to homoeopathic drugs.

Adolescent↗
PubMed1986

Relationships between avian exposure, humoral immune response, and pigeon breeders' disease among Scottish pigeon fanciers.

In a large scale clinical survey of Scottish pigeon fanciers, 277 people completed a detailed questionnaire and provided a venous blood sample. There were 29 (10.4%) who fulfilled the clinical criteria for pigeon breeders' disease used in the study and 84 (30.3%) who showed a significant serum IgG antibody response to pigeon gammaglobulin (4 micrograms/ml) and were considered to have been sensitised. Increasing exposure was associated with a progressive tendency towards sensitisation, but the intensity of the antibody response was related to the presence of symptoms and not the degree of exposure. Thirteen out of 15 subjects in the survey with a serum concentration of antipigeon IgG greater than 60 micrograms/ml fulfilled the clinical criteria for pigeon breeders' disease, and those affected within 10 years of starting the hobby had the highest mean antibody response. Accurate quantitation of antibody response is therefore helpful in the investigation of pigeon breeders' disease. The radioimmunoassay provides a quantitative method for determining antibody response that can be used in the routine screening of pigeon fanciers and in serial monitoring of their response.

Adult↗
PubMed1985

Effect of cigarette smoking on the antibody response to inhaled antigens and the prevalence of extrinsic allergic alveolitis among pigeon breeders.

There was a reduced prevalence of symptoms of Extrinsic Allergic Alveolitis (EAA) among the cigarette smokers in a survey of 102 volunteer pigeon breeders. These smokers had a significantly lower antibody response against the inhaled antigens associated with the disease; only one of twenty-three smokers (4.3%), but thirty-nine of sixty-five non-smokers (55.4%) had elevated serum IgG antibody levels, despite similar degrees of avian exposure in each group. The appearance of antibody in six of fourteen ex-smokers (42.9%) suggested that the apparent inhibitory effect of smoking on the antibody response was reversible. The smoking group had lower total serum IgG and IgA, higher serum IgD, and their total IgM and IgE levels were similar to the nonsmokers.

Alveolitis, Extrinsic Allergic↗
PubMed1984

Pulmonary hypersensitivity in the alginate industry.

Salts of alginic acid are complex polymerised polysaccharides which are chemically extracted from seaweed. Workers in the alginate industry are exposed to dust from dried milled seaweed and pure alginate compounds. In this survey of one of the two factories in Britain producing alginates, we found evidence of pulmonary hypersensitivity to seaweed dust in seven per cent of the total work force, and evidence of precipitating antibody to sodium alginate and seaweed extracts in the serum of 4.5 per cent of the work force. Challenge testing of a number of employees with symptoms showed a dual response with immediate airways obstruction, and a later loss of lung volume, with associated impairment of transfer factor.

Alginates↗
PubMed1984

Antibody measurement in extrinsic allergic alveolitis.

Serum IgG antibody against purified avian antigens was quantified by radioimmunoassay in 507 active pigeon fanciers, of whom 110 had documented Pigeon Breeders Disease (PBD). The incidence of PBD increased from 3.7% in the antibody-negative group to 78% of those with IgG antibody greater than 30 micrograms/ml. The highest levels of antibody tended to occur in subjects with relatively short avian exposure, and a significant correlation between decreasing antibody levels and increasing years of avian contact was demonstrated, which was unrelated to age or smoking history. The antibody -positive subjects had lower daily hours of avian contact and this group which contained most of the PBD subjects demonstrated some self-regulation of antigen exposure.

Age Factors↗