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Biomedical subjects

A D Curran

Publications and source records attributed to A D Curran.

At least 19 recordsLinked to original sources

Sensitization to king scallop (Pectin maximus) and queen scallop (Chlamys opercularis) proteins.

OBJECTIVE: To report a case of occupational asthma and urticaria due to the queen scallop (Chlamys opercularis) and king scallop (Pectin maximus). BACKGROUND: A 40-year-old female worked in a shellfish-processing plant, handling king and queen scallops for 5 years. At the time of investigation, she described a 2-year history of work-related respiratory symptoms. METHODS: Serial peak expiratory flow rate readings were recorded and an OASYS study completed. A workplace visit was undertaken and specific immunoglobulin (IgE) radioallergosorbent (RAST) testing of scallop extracts was performed. RESULTS: The OASYS study was consistent with occupational asthma. RAST testing demonstrated evidence of specific sensitization (IgE) to queen and king scallop. There was also some cross-reactivity observed with other shellfish (prawns and crabs). CONCLUSION: Workers exposed to aerosols from scallop species are at risk of occupational asthma and require effective respiratory health surveillance.

Adult↗

Prevalence of sensitisation to cellulase and xylanase in bakery workers.

AIMS: To assess the prevalence of sensitisation to a range of exogenous fungal enzymes used in bakeries, and determine the relation between sensitisation and work related symptoms. METHODS: Serum samples (n = 135) from a previous cross sectional study investigating the prevalence of respiratory symptoms and sensitisation to dust components, were reanalysed for specific IgE to the mixed enzymes cellulase, hemicellulase, and xylanase. RESULTS: Eight (6%) of sera tested had detectable specific IgE to mixed enzymes (excluding fungal alpha-amylase) and 16 (12%) to fungal alpha-amylase. A significant increase (p = 0.03) in nasal symptoms was found in those workers sensitised to enzymes (including alpha-amylase and the mixed enzymes, but with or without sensitisation to wheat flour) when compared to those sensitised to wheat flour alone. Both groups had significantly greater levels of nasal symptoms in comparison to those with no evidence of sensitisation. CONCLUSIONS: The association between specific IgE to mixed enzymes, and an increased prevalence of nasal symptoms in individuals sensitised to enzymes, highlights the importance of measuring sensitisation to the full range of exogenous enzymes used in the baking industry, as well as to wheat flour.

Cellulase↗

Monocyte CD14 response following endotoxin exposure in cotton spinners and office workers.

BACKGROUND: Monocyte cell surface CD14 acts as the major lipopolysaccharide (LPS) binding structure, and as such is of interest in the etiology of LPS induced disease. METHODS: The objective was to assess change in monocyte cell surface CD14 and CD4+ CD25+ lymphocytes in a group of cotton workers exposed to LPS over a working week, and to compare this to changes in office workers. Twenty-five cotton workers and nine office workers were studied. Monocyte CD14 fluorescence was measured by flow cytometry, on samples taken pre-shift on a Monday morning (baseline/pre-exposure), and subsequently after 6 and 72 hr. The majority of cotton workers were exposed to at least 1 EU/m(3) of endotoxin over a working shift, and some highly exposed (between 100 and 400 EU/m(3)). RESULTS: After 6 hr of work in the mill, cotton workers developed a significant upregulation in CD14 in comparison to office workers (P = 0.016), whereas CD14 expression had returned to levels not significantly differing from the office workers at 72 hr after first work exposure (P = 0.426). CONCLUSIONS: We propose that CD14 expression on monocytes may help to determine the mechanism of action of lipopolysaccharide in producing respiratory ill health, and may ultimately play a role in monitoring the health effect associated with LPS exposure in the workplace.

Adult↗

Respiratory symptoms, lung function and cell surface markers in a group of hemp fiber processors.

BACKGROUND: Hemp dust exposure is associated with byssinosis and accelerated lung loss in longitudinal studies. The immunological changes associated with hemp dust exposure are less well understood. METHODS: We studied a small group of current male hemp processors with a mean age of 43 years. Questionnaire data, lung function, serial FEV(1) and blood were collected from all workers. RESULTS: In total, seven workers (64%) complained of at least one respiratory symptom (one with byssinosis). The mean percentage predicted FEV(1) was 91.5, FVC 97.7, PEF 92.1, and FEF(25-75) 79.5. Serial FEV(1) measurements in the two workers with work-related respiratory symptoms revealed a mean change in FEV(1) on the first working day of -12.9%. This contrasted with +6.25% on the last working day. Respective values for the two workers without work-related symptoms were -1.4 and +3.2%. CONCLUSIONS: Lung function changes and abnormalities in a profile of cell surface activation markers and antibodies were noted to relate to the presence of work-related respiratory symptoms, not seen in the control group.

Adult↗

Mechanisms of isocyanate sensitisation. An in vitro approach.

Although there is an abundance of clinical evidence which suggests that the inhalation of isocyanates can induce occupational asthma, the immunological basis for the disease is not understood. We have investigated immune cell responses to isocyanate using the cell line mono-mac-6, by measuring the production of hydrogen peroxide, and the expression of ICAM-1 following challenge with isocyanates and their corresponding amines. We observed an increase in the levels of intracellular peroxide, in addition to an upregulation of ICAM-1 expression (P<0.05), following cell stimulation with isocyanates, which was not apparent following stimulation with amines. From the results of this study we hypothesise that the production of reactive oxygen species (ROS) by monocytic cells at the site of exposure to an isocyanate may have two potential outcomes. The first is that the ROS may contribute to tissue damage at the site of inflammation, and then secondly, it is possible this production of hydrogen peroxide may also induce the upregulation of adhesion markers on monocytic cells, specifically ICAM-1, which may potentiate the infiltration and adhesion of cells at the site of inflammation.

Cyanates↗

The development of an antibody to trimellitic anhydride.

Acid anhydrides are a group of highly reactive chemicals used widely in the formulation of paints and plastics. Exposure to acid anhydrides causes several occupational lung diseases such as pneumonititis and asthma. Whilst anhydrides, specifically trimellitic anhydride (TMA), have been shown to bind to lung tissue in an animal model, further investigation has been hampered by the lack of a reagent which would enable the identification of primary target proteins for the binding of TMA. Our objective was to develop an antibody to TMA which would enable in vitro studies of TMA interactions with lung epithelial proteins. We developed a monoclonal antibody which binds solely to TMA. We have demonstrated that the antibody can be used to detect TMA bound to different human proteins with little non-specific binding to unconjugated proteins. We then exposed cells of the A549 lung epithelial cell line to TMA in vitro and have shown by western blotting that binding occurs in the 20-35 Kd weight range. We have developed a specific and sensitive reagent to detect TMA bound to proteins. We have used this to show that when TMA is incubated with a lung epithelial cell line, that the TMA binds to proteins with a restricted molecular weight range. These results suggest that the current paradigm for the detection of IgE to small molecular weight reactive chemicals, which presupposes that the chemical binds to serum albumin, may need further investigation.

Animals↗

Measurement of personal exposure to aerosols of Nephrops norvegicus (scampi) using a monoclonal-based assay.

BACKGROUND: The industrial processing of scampi (Nephrops norvegicus) generates bioaerosols which can cause occupational respiratory disease in exposed individuals. The objective of this study was to develop a monoclonal antibody-based immunoassay to measure scampi proteins collected using standard personal air sampling methods. METHODS: A monoclonal antibody was generated which predominantly bound to a single 97 Kd scampi protein, which we have shown to be a major allergen. This protein was shown by SDS PAGE immunoblotting to be present in various aqueous extracts from wastes produced during scampi processing. A quantitative immunoslotblot method was developed to quantify scampi from air sample filters. RESULTS: We demonstrated the utility of this method by showing a significant difference (P = 0.015) in the level of exposure of two groups of 12 workers processing scampi at a traditional open workstation (GM = 607 ng m(-3)) and at an enclosed workstation (GM = 451 ng m(-3)). CONCLUSION: We conclude that this assay can be used, in conjunction with health surveillance, to monitor exposure and the efficacy of measures to reduce exposure to airborne scampi allergen in an occupational environment.

Aerosols↗

Provision and perception of occupational health in small and medium-sized enterprises in Sheffield, UK.

A random sample of managers of small and medium-sized enterprises (SMEs) was selected from a database of businesses in Sheffield, UK. They were invited to take part in a study to evaluate the provision and perception of occupational health in SMEs in Sheffield. The study used an interviewer-led questionnaire, which collected quantitative and qualitative data; each interview took approximately 40 min to complete. Several approaches to recruitment were adopted during the study. Twenty-eight managers were interviewed over the 6 month study period. All of the SMEs employed <250 people; 43.2% did not have or had never reviewed a written health and safety policy. Only 18% had a written occupational health policy; 14.4% employed the services of a part-time occupational health physician; 7.2% employed a health and safety advisor; and 10.8% employed a part-time occupational health nurse. Twenty-five per cent had a nominated person responsible for occupational health and 67% thought that a doctor or nurse would be the best person to provide an occupational health service. Twenty-eight per cent of the companies carried out some form of pre-employment screening and 14.2% carried out health promotion. Fifteen (53.5%) collected some form of health related absence data. Eight companies (28.6%) organized a formal induction programme for all new employees. Further work should be undertaken in an attempt to improve access to local industry and particularly to SMEs. This study has clearly shown that access is possible, but different strategies of approach were required before a workable strategy could be found. Undoubtedly, this access can be improved by better understanding of the interaction between researchers, occupational health providers and local managers of SMEs.

Attitude to Health↗

Development and validation of a monoclonal based immunoassay for the measurement of fungal alpha-amylase: focus on peak exposures.

The inhalation of flour dust has been implicated in the induction of sensitisation and elicitation of respiratory symptoms, such as asthma in bakers. In addition to the cereal allergens present in wheat flour, enzymes in flour improvers, in particular fungal alpha-amylase, are now known to be a significant cause of respiratory allergy in the baking industry.A monoclonal antibody based enzyme-linked immunoassay (ELISA) was developed using two monoclonal antibodies that recognised two distinct epitopes of the fungal alpha-amylase enzyme. The ELISA had an inter-assay variation of 12.0% at 1360 pg/ml and 12.8% at 564 pg/ml and intra-assay variation of 4.9% at 1340 pg/ml and 6.1% at 504 pg/ml. The assay had a sensitivity of 200 pg/ml. Competitive inhibition assays confirmed that the monoclonal antibodies had no cross reactivity with other enzymes used in the baking industry and could distinguish added fungal alpha-amylase from cereal amylase. We assessed the levels of exposure to dust, total protein and fungal alpha-amylase in four UK bakeries ranging in size and technical capabilities. Within the bakeries we surveyed, workers were exposed to variable levels of inhalable dust (0.8-39.8 mg/m3), total protein (0-5.7 mg/m3) and fungal alpha-amylase (0-29.8 ng/m3). Consecutive 15 min personal samples taken over a 1 h period demonstrated that the ELISA could measure fungal alpha-amylase exposure in such a 15 min period. Short term peak exposures to fungal alpha-amylase could be identified which may contribute to the sensitisation in individuals who appear to have low exposure levels if measured over a full shift period.

Antibodies, Monoclonal↗

Assessment of exposure to organic dust in a hemp processing plant.

The aim of this preliminary study was to assess exposure to various constituents of the organic dust generated during the processing of hemp in a small group of exposed workers. Airborne levels of inhalable dust, endotoxin and soluble protein, and the respirable, thoracic and inhalable fractions of fungal, bacterial and actinomycete contamination were measured in the personal breathing zone of exposed workers. Inhalable dust, endotoxin, fungal and bacterial contamination all exceeded levels found in similar vegetable fibre processing factories, since inhalable dust levels ranged from 10.4 to 79.8 mg/m(3) and inhalable bacterial levels between 4.7 and 190 x 10(6) cfu/m(3). Soluble protein and endotoxin (r=0.99, P<0.0001), endotoxin and inhalable dust (r=0.94, P<0.005) and inhalable dust and protein (r=0.98, P<0.0001) were significantly correlated, suggesting that there was little variation in the composition of the dust from different sites or activities around the workplace. Andersen sampling gave an indication of background microbe levels, although no attempt was made to identify the specific microorganisms as all plates were significantly overgrown. Airborne assessments demonstrated that exposures were highly task specific. For example, sweeping the floor generated the highest exposure levels of total dust, protein, endotoxin, bacteria and fungi. Therefore, we have shown that a modern-day hemp fibre processing plant produces significant quantities of respirable dust which is highly contaminated with endotoxin and microorganisms. This organic dust has the potential to cause a range of ill health problems.

Air Microbiology↗

Colophony: an in vitro model for the induction of sensitization.

BACKGROUND: The potential of colophony fumes from soldering flux to induce asthma has been known since the 1970s, however, no direct in vitro or in vivo evidence has been reported. The present study investigated the potential of colophony to stimulate human phagocytic cells to produce reactive oxygen species. METHODS: The human cell line HL-60 was differentiated to produce cells with a monocyte-like and a neutrophil-like phenotypes. A number of procedures were used to confirm the phenotype of these differentiated cells including morphology, esterase activity, flow cytometry and phagocytosis. The potential of colophony to stimulate human phagocytic cells to produce reactive oxygen species was monitored using flow cytoenzymology. RESULTS: We were able to show that intracellular peroxide levels were increased in both monocyte-like and neutrophil-like cells, but not in undifferentiated HL-60 cells following the addition of colophony. CONCLUSIONS: The resin acid epoxides and hydroperoxides which have been suggested to be sensitizers in contact allergy, are degraded during the soldering process. However, conditions for the oxidation of colophony may occur in vivo as a result of the colophony-induced oxidative burst from neutrophils and monocytes. These oxidation products may then interact with body proteins to further initiate immune responses. Therefore for the preparation of low molecular weight chemical (LMWC)-protein conjugates, consideration must be taken to determine whether the LMWC is undergoing a reaction in vivo before it is interacting with body proteins.

Cell Differentiation↗

The in vitro percutaneous penetration of chlorpyrifos.

Chlorpyrifos is a widely used organophosphate pesticide. In order to study the pharmacokinetics of the penetration of chlorpyrifos through human skin we measured the percutaneous penetration of chlorpyrifos through human skin using an in vitro flow through apparatus. The chlorpyrifos was applied to the skin as a commercial concentrate or as a reference standard dissolved in ethanol. There was a significant difference (P=0.03) between the rate of penetration from the commercial concentrate (9.0 nmoles cm(-2) h(-1)) and that from the reference standard (4.9 nmoles cm(-2) h(-1)). Each experiment was run for 24 h. The recoveries from experiments where chlorpyrifos was applied to the skin as a commercial concentrate and as a reference standard dissolved in ethanol were, respectively, in total 91 and 87% of the applied dose of which 15 and 10% was recovered from the skin, 56 and 66% was recovered from the surface of the skin and 20 and 11% was recovered from the receptor fluid. There was a significant difference in the recoveries from the skin but there was no significant difference in the recoveries from the surface of the skin. We concluded that the majority of a dermal dose of chlorpyrifos was still present at or in the surface of the skin 24 h after application of a dermal dose. Because chlorpyrifos was recovered from the skin after 24 h, it is possible that the skin could act as a reservoir and release chlorpyrifos over a longer period. We also conclude that the solvent vehicle for chlorpyrifos can affect the rate of penetration of the pesticide.

Administration, Cutaneous↗