Biomedical subjects
R D Tee
Publications and source records attributed to R D Tee.
Respiratory symptoms, lung function, and sensitisation to flour in a British bakery.
A survey of dust exposure, respiratory symptoms, lung function, and response to skin prick tests was conducted in a modern British bakery. Of the 318 bakery employees, 279 (88%) took part. Jobs were ranked from 0 to 10 by perceived dustiness and this ranking correlated well with total dust concentration measured in 79 personal dust samples. Nine samples had concentrations greater than 10 mg/m3, the exposure limit for nuisance dust. All participants completed a self administered questionnaire on symptoms and their relation to work. FEV1 and FVC were measured by a dry wedge spirometer and bronchial reactivity to methacholine was estimated. Skin prick tests were performed with three common allergens and with 11 allergens likely to be found in bakery dust, including mites and moulds. Of the participants in the main exposure group, 35% reported chest symptoms which in 13% were work related. The corresponding figures for nasal symptoms were 38% and 19%. Symptoms, lung function, bronchial reactivity, and response to skin prick tests were related to current or past exposure to dust using logistic or linear regression analysis as appropriate. Exposure rank was significantly associated with most of the response variables studied. The study shows that respiratory symptoms and sensitisation are common, even in a modern bakery.
Evidence of allergic hypersensitivity to chironomid midges in an English village community.
Some chironomid (non-biting) midges contain potent human allergens, principally in the form of insect haemoglobins. In view of previously demonstrated immunological cross-reactivity between some different midge species, the possible role of British midges in allergic disease was studied. The chosen site, Farmoor near Oxford, is a village that has been subject to several annual nuisance midge swarms since the construction of an adjacent water-supply reservoir in 1964, which was extended in 1975. The incidence and severity of hypersensitivity in the community was assessed by questionnaire survey, skin-prick testing, radio-allergosorbent tests (RAST) and RAST inhibition, and enzyme-linked immunosorbent assays (ELISA) and ELISA inhibition, using extracts of locally caught adult midges (Tanytarsus sylvaticus, T. bathophilus and Chironomus anthracinus) and laboratory cultured larvae (C. riparius). These tests revealed a low but significant level of midge-related hypersensitivity with skin-prick results showing seasonal fluctuations, but this seasonality was not confirmed with an IgE RAST. A correlation between IgE levels and relevant symptoms was found (P less than 0.01) using RAST, but not between IgE and skin-test results. Enzyme-linked immunosorbent assay results did not correlate with any other parameter measured. The incidence and severity of allergic reactions to the midges tested in this community was low.
Laboratory animal allergy in a pharmaceutical company.
A cross sectional survey was carried out on 138 workers exposed to laboratory animals. Sixty (44%) had symptoms in a self completed questionnaire that were consistent with laboratory animal allergy (LAA) of whom 15 (11%) had chest symptoms. There was a positive skin prick test to one or more animal urine extracts (rat, mouse, guinea pig, rabbit) in 13% and 38% had a positive radioallergosorbent test to urine extract. LAA chest symptoms were almost five times more common in atopic than non-atopic subjects (who were distinguished by skin test response to common, non-animal aeroallergens). A positive skin test to animal urine was associated with LAA chest symptoms and with atopy. Nose, eye, or skin symptoms without chest symptoms were not associated with atopy. There was an inverse relation between duration of employment at the firm and LAA chest symptoms, suggesting selection of affected people out of employment with animals.
Smoking, atopy, and laboratory animal allergy.
This study examined data from three cross sectional surveys of 296 laboratory workers exposed to small mammals. Four indices of laboratory animal allergy were studied: symptoms suggestive of occupational asthma, symptoms suggestive of any occupational allergy, skin weals to animal urine extracts, and serum binding in radioallergosorbent tests with urine extracts. Pooled data from the three surveys showed an association between smoking and all indices except radioallergosorbent tests; the association was significant for symptoms of occupational asthma. One of the three surveys consistently showed a stronger association of allergy indices with smoking than with atopy (defined on skin tests with non-animal aeroallergens). Associations with smoking persisted after stratifying by atopic status, suggesting that smoking may be a risk factor for laboratory animal allergy.
Occupational allergy to locusts: an investigation of the sources of the allergen.
Allergic symptoms occur commonly in subjects working closely with locusts and are associated with specific IgE antibody. Extracts of intact locusts (Schistocerca gregaria and Locusta migratoria) were used to identify specific IgE antibody, to define the major allergens of the locust and their sources, and to estimate aeroallergen concentration in the working environment. With questionnaire, skin prick tests, and specific IgE measurements, 35 individuals, working in a research center, were surveyed. Of the 15 currently exposed individuals, contact with locusts provoked asthma, rhinitis, and contact urticaria in five, rhinitis and urticaria in three, and rhinitis alone in one individual. Symptoms provoked by locusts and skin test reactions to locust extracts were associated with specific IgE antibody in the serum. The "immunoblot" technique demonstrated the presence of multiple allergens in the locust extracts of approximately 68, 66, 54, 43, 37, 29, and 18 K daltons molecular weight. Locust antigen was identified in the atmosphere by means of an immunochemical method involving elution of high-volume air-sampler filters exposed in the locust breeding room and analysis of eluate allergen content by RAST-inhibition assays. Logit transformation of RAST-inhibition lines demonstrated that the filter extract shared a common slope with the locust extract and with an extract of locust gut. This gut extract also shared a common slope with extracts of locust feces and peritrophic membrane. The major source of allergen appears to be the peritrophic membrane that is present in the gut and is excreted surrounding the feces.
Respiratory allergy to inhaled bat guano.
In the Sudan many asthmatic patients attribute their symptoms to inhalation of bat droppings. Design of the roofs of many Sudanese buildings allows black bats to roost; guano drops through cracks in the ceiling into the rooms below where it can be inhaled and cause allergic respiratory disorders. Seven atopic patients seen at Sennar Hospital with bat-related case-histories were investigated. Six had bronchial asthma and allergic rhinitis and one had asthma alone. Extracts of yellow hairy bat, black bat, and bat droppings were made. All seven patients had a positive skin prick test and specific IgE antibodies (RAST) to bat droppings. Three patients also had a positive RAST to both yellow and black bats and one patient to yellow bat. Droppings are probably the major allergen source in bat-related respiratory allergy.
Cross-reactivity between antigens of fungal extracts studied by RAST inhibition and immunoblot technique.
We have used the RAST-inhibition technique in homologous and heterologous inhibitions of the Aspergillus fumigatus, Alternaria tenuis, and Cladosporium herbarum RAST assays followed by the immunoblot technique to assess the degree of shared allergenic determinants in these extracts. In the Aspergillus RAST, there was little or no inhibition with Cladosporium and Alternaria, but considerable cross-reactivity was found between Alternaria and Cladosporium. Inhibition by Alternaria of the Cladosporium RAST was found in a dose-dependent fashion in one serum, whereas all four sera in the Alternaria RAST were inhibited by Cladosporium in this fashion. Logit transformation of the Alternaria RAST-inhibition curves produced common slopes with Alternaria and Cladosporium in three of the four sera, indicating their immunologic identity. The immunoblot technique confirmed the degree of cross-reactivity found by RAST inhibition among the molds. This evidence of common allergenic determinants in these fungi could help to explain the observation that mold-allergic patients often have skin test reactions to several fungi.
Further characterisation of allergens associated with hypersensitivity to the "green nimitti" midge (Cladotanytarsus lewisi, Diptera: Chironomidae).
Chironomid midges are small (2-15 mm) non-biting flies, characteristically seen swarming by water at dusk. Allergens of the "green nimitti" midge, Cladotanytarsus lewisi (Freeman) (Diptera: Chironomidae), a cause of widespread hypersensitivity in the Sudan, were isolated and partially characterized by Sephacryl S200 chromatography. The allergenicity of the fractions was identified by "rocket" autoradiography, RAST inhibition, skin "prick" tests, and the immunoblot technique. The fractions were further analysed by isoelectric focusing and SDS-PAGE. Two major allergens with pI's ranging from 4.3 to 6.0 were identified and had molecular weights of approximately 17,000 and 32,000 daltons, sizes compatible with their being monomeric and dimeric haemoglobins. Since chironomids occur in nuisance numbers worldwide and their haemoglobins have been shown to produce severe hypersensitivity reactions in man, they should be seen as an important potential cause of environmental and occupational allergy.
Didymella exitialis and late summer asthma.
4 patients in whom Didymella exitialis seemed to be an important cause of their asthma were investigated. All 4 patients had immediate skinprick test reactions and specific IgE antibody to D exitialis and Alternaria alternata. Inhalation of a soluble extract of D exitialis provoked immediate asthmatic reactions in these 4, but not in a skin-prick-test-negative volunteer. Radioallergosorbent inhibition studies with D exitialis and A alternata showed self and cross inhibition, which suggested shared antigens. During summer, 1983, 1 of the 4 recorded peak expiratory flow rate (PEFR) twice a day. Spore counts of D exitialis and A alternata were made during this time. Falls in PEFR occurred when D exitialis spore counts increased, usually after a rainfall. Of 34 allergy clinic patients, 6 had skin-prick test reaction to both fungi, but 2 had reactions to A alternata only and 3 to D exitialis only, which suggests the existence of specific antigens. D exitialis seems to be a cause of late summer asthma. Its importance is not known, but allergy to it may contribute to asthma following thunderstorms.
Occupational allergy to the common house fly. (Musca domestica): use of immunologic response to identify atmospheric allergen.
A 48-year-old scientific worker developed rhinitis that occurred when she entered the housefly (Musca domestica) rearing room where she worked. She was found to have specific IgE antibody to M. domestica in her serum by RAST. She was relocated at work and avoided further occupational exposure to M. domestica. The level of specific IgE decreased in serial samples but subsequently increased after her inadvertent reexposure at work. Extracts of fly-cage dust and of high volume atmospheric samples from the fly-rearing room inhibited the M. domestica RAST in a dose-dependent fashion. After logit transformation the lines of inhibition of the fly cage dust and of the atmospheric samples were parallel and steeper than the self-inhibition by M. domestica, implying the cage dust and atmospheric samples shared antigens not present in the M. domestica extract. This method of monitoring atmospheric antigen has considerable potential for evaluating the effectiveness of environmental change in the workplace.
Evidence for haemoglobins as common allergenic determinants in IgE-mediated hypersensitivity to chironomids (non-biting midges).
Chironomids (non-biting midges) are known to cause IgE-mediated hypersensitivity in man. This study compares the cross-reactivity between the chironomid midge Cladotanytarsus lewisi ('green nimitti'), a widespread cause of allergy in the Sudan and Chironomus riparius (= thummi, CTT) where larvae are used as pet fish food and where haemoglobins were previously shown to be major allergens. As with C. riparius, immature forms of C. lewisi also contain allergenic material since skin test responses to larval, pupal and adult extracts were obtained in Sudanese individuals. Crossed radioimmunoelectrophoresis of the C. lewisi larval and pupal extracts indicate that they contain a higher proportion of the allergenic fractions than adults. Further evidence of common allergen determinants between C. lewisi and C. riparius were obtained by the demonstration of positive skin-prick tests, in Sudanese patients, to extracts of larval, adult and isolated haemoglobin extracts of C. riparius. Cross-reactivity between C. lewisi and C. riparius was also demonstrable by RAST inhibition studies. A dose-dependent inhibition was observed using both the C. lewisi adult midge RAST and the C. riparius haemoglobin RAST, the two respective antigens, and sera from individuals hypersensitive to either C. lewisi or C. riparius. Due to the immunological cross-reactivity found between these distantly related species, we conclude that chironomids should be seen as significant environmental and occupational allergens.
Partial characterization of allergens associated with hypersensitivity to the 'green nimitti' midge (Cladotanytarsus lewisi, Diptera: Chironomidae).
Allergens in extracts of the 'green nimitti' midge, Cladotanytarsus lewisi Freeman (Diptera: Chironomidae), a cause of widespread hypersensitivity in the Sudan, were isolated and partially characterized by assays which depend on the binding of 125I-anti-IgE to allergen-IgE complexes. These methods included RAST inhibition, crossed radioimmunoelectrophoresis (CRIE) and rocket radioimmunoelectrophoresis (RRIE). Following Sephadex G100 chromatography the 'major peak' of allergenicity as determined by RAST inhibition, RRIE and SDS-PAGE was associated with molecules of approximately 17 000 daltons. The peak eluting at Vo contained material of molecular weight 66 000 daltons which also bound 125I-anti-IgE, but had only 61% of the activity of the 'major peak' by RAST inhibition. By isoelectric focusing and RRIE of fractions obtained by chromatofocusing with polybuffer exchanger 94, the 'major peak' was associated with multiple bands with a pI range of 3.5-5.5. These results indicate that the major allergens from C. lewisi are a group of closely related acidic peptides.
Immediate-type skin reactivity to extracts of the 'green nimitti' midge, (Cladotanytarsus lewisi), and other chironomids in asthmatic subjects in the Sudan and Egypt.
Skin 'prick' tests with an extract of the 'green nimitti' midge, Cladotanytarsus lewisi (Freeman), a potent airborne allergen associated with asthma and rhinitis in the Khartoum area, were undertaken on asthmatic subjects in several localities in the Sudan and Egypt in order to provide further information on the extent of this allergic problem. In the Sudan skin-test-positive individuals were identified in the Khartoum area, Kosti, Sennar, Wad Medani, Shendi and Atbara, and in Egypt at Aswan, Luxor and Qena. A number of asthmatic individuals giving a positive reaction to C. lewisi were also tested with extracts of seven sub-dominant species of Nilotic Chironomidae. There appeared to be a limited degree of cross-reactivity with these species, particularly Dicrotendipes fusconotatus (Kieffer), Procladius noctivagus (Kieffer) and Conchapelopia cygnus (Kieffer). The numbers of C. lewisi sensitive subjects giving positive skin-tests to these other species were ten out of 20, 12 out of 28 and 12 out of 29 respectively. In contrast, only five out of 31 reacted to Paracladopelma graminicolor (Kieffer), five out of 24 to Cladotanytarsus pseudomancus (Goetghebuer), three out of 32 to Nanocladius vitellinus (Kieffer) and two out of 28 to Cryptochironomus neonilicola (Freeman). These results indicate that Cladotanytarsus lewisi is a major source of chironomid allergen(s) in these asthmatic subjects and that hypersensitivity to C. lewisi is probably far more widespread than originally envisaged.
Specific serum IgE antibodies to bacterial antigens in allergic lung disease.
A radio-allergosorbent test (RAST) to measure specific IgE antibodies in man to whole bacterial cells of Streptococcus pneumoniae, Staphylococcus aureus and Haemophilus influenzae was developed to investigate different well-defined lung diseases (chronic bronchitis, allergic bronchopulmonary aspergillosis (ABPA), bronchial asthma allergic rhinitis, cystic fibrosis) and also in urticaria as compared with non-atopic blood donors. In addition, total IgE values and skin prick tests were assessed in these patients. The ABPA group gave the highest specific IgE RAST scores to all three bacteria, whilst the chronic bronchitis and cystic fibrosis groups also gave raised RAST scores with H. influenzae. There was a positive correlation between the patients' Sta. aureus and Str. pneumoniae immediate-type skin reactions and their RAST scores and total serum IgE concentrations, but there was only a low incidence of immediate-type skin test positivity to H. influenzae.
Immunological investigations of Candida albicans in respiratory disease.
1. Tests against rabbit antiserum to Candida albicans showed about 40 protein antigens in cytoplasmic extract compared with two in a commercial test extract, which contained mainly polysaccharide (mannan) antigens. 2. Positive precipitin tests to the mannan preparation were recorded in 40% of 56 asthmatics on systemic corticosteroids and 37% of 56 rhinitis patients not so treated. The titres were slightly higher in the corticosteroid group. There was no increase in precipitins over 0-9 months in asthmatics treated with beclomethasone dipropionate aerosol (BDA) by inhalation, or over 0-12 months in rhinitis patients treated with BDA nasal spray. No positive reactions to the purified protein fraction were recorded. 3. Radioallergosorbent tests for specific IgE antibody showed a higher incidence of positive results with whole C. albicans yeast cells than with purified cytoplasmic protein. There was a higher incidence of positive results to protein in patients on systemic corticosteroids than in the other patients. No change in incidence occurred in asthmatics on BDA. The number of positive results in 56 rhinitis patients increased on BDA from 28 to 37 for yeast cells, and from 7 to 16 for cytoplasmic protein. This was attributed to C. albicans challenge tests. 4. Specific IgA antibodies to yeast cells were detected in 48/56 asthmatics on systemic corticosteroids, and there were no significant changes over 0-9 months on BDA. The corresponding figures for rhinitis patients were 25/56, and again there were no significant changes over 0-12 months on BDA.
Some immunologic aspects of leprosy.
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