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Biomedical subjects

J Pepys

Publications and source records attributed to J Pepys.

At least 19 recordsLinked to original sources

Allergic asthma to Bacillus subtilis enzyme: a model for the effects of inhalable proteins.

The passage of 24 years since the diagnosis of allergic asthma in heavily exposed workers and in a few consumers due to dusty enzyme preparations of Bacillus subtilis compounded with laundry powder makes it possible to review objectively the many problems it raised. It emphasizes the lessons to be learned, relevant to inhalable enzyme products and to other inhalable proteins in general. Occupational allergic respiratory diseases were little studied at the time and the enzyme problems stimulated interest in what has now become a well-established and important field of medicine involving not only protein allergens but low molecular weight chemicals as well.

Asthma

Clinical correlations between long-term (IgE) and short-term (IgG S-TS) anaphylactic antibodies in atopic and 'non-atopic' subjects with respiratory allergic disease.

The sera of atopic and non-atopic persons with allergic pulmonary disorders were examined for long-term sensitizing, IgE and short-term sensitizing heat-stable (S-TS) antibodies which were present separately or together in the sera of some patients sensitive to antigens such as budgerigar serum proteins and Aspergillus funigatus. In fourteen atopic patients with extrinsic asthma, six had both types of antibody to common allergens, and of nine non-atopic patients with crytogenic (intrinsic) asthma, four had only heat-stable short-term sensitizing antibodies. The sera of atopic subjects with type I prick test reactions and positive RAST's, showed specific IgE antibody by baboon PCA tests to budgerigar serum proteins, A. funigatus, Timothy grass pollen extract and hen egg extract, and not to Dermatophagoides farinae, possibly because of naturally occurring mite antibodies in the baboon. The sera of non-atopic asthmatics, who had given negative prick test but positive immediate, dual or late intracutaneous tests, and only late asthmatic reactions, contained precipitins in most cases and gave little or no RAST reaction. On baboon PCA these sera contained either, S-TS antibody alone, or S-TS plus long-term sensitizing antibody, or long-term sensitizing antibody alone. Some of the sera with long-term sensitizing antibody contained blocking antibody which could diffuse away in the 24 hr delay for the baboon PCA test and could also be responsible for the negative RAST. Tests with insoluble anti-IgE immuno-adsorbents on two sera from persons sensitive to aspergillus confirmed that the S-TS activity was not due to IgE, and on two sera with negative RAST and negative prick tests to budgerigar serum antigens confirmed that the 24 hr monkey PCA responses were due to IgE.

Allergens

Toluene di-isocyanate-induced asthma. I. Reactions to TDI, MDI, HDI and histamine.

A group of twenty four workers handling di-isocyanates and with respiratory disease were investigated by occupational-type bronchial provocation tests for sensitivity to toluene di-isocyanate (TDI), to which all were exposed, and to diphenylmethane di-isocyanate (MDI) and hexamethylene di-isocyanate (HDI). Sixteen gave asthmatic reactions to TDI and eight of these also reacted to MDI. Four of the eight TDI and MDI reactors had histories of exposure only to TDI, and of them two reacted also to HDI. Of nine subjects tested with HDI, three gave asthmatic reactions, and all three also reacted to TDI and MDI. Thus reactions to MDI and HDI were elicited only in the TDI reactors. The possibility of specific sensitivity to these and other di-isocyanates requires tests in subjects exposed to them and not to TDI.

Asthma

Toluene di-isocyanate-induced asthma. II. Inhalation challenge tests and bronchial reactivity studies.

In sixty-three workers exposed to toluene di-isocyanate (TDI), no overall differences in bronchial reactivity to histamine inhalation and to exercise testing were found between the total groups of positive and negative TDI reactors to provocation tests. A subgroup of TDI highly sensitive subjects reacting to very low concentrations (less than or equal to 0.001 p.p.m.) were more sensitive to both histamine and exercise than the group who were less sensitive to TDI, and who reacted to higher concentrations (0.002--0.02 p.p.m.) than the group of non-reactors. There were, however, in the last group a number of subjects with high degrees of histamine reactivity who did not react to the TDI. These findings suggest that, on the one hand, the asthmatic reactions to TDI cannot be attributed solely to non-specific mechanisms and, on the other, that in subjects with high degrees of specific sensitivity non-specific mechanisms may also be playing a part.

Adult

Passive transfer in man and the monkey of Type I allergy due to heat labile and heat stable antibody to complex salts of platinum.

Passive transfer (P-K) tests have been performed in man and monkeys with sera from a group of six refinery workers sensitive to ammonium hexachloroplatinate and tetrachloroplatinite. Positive (P-K) prick test reactions were elicited in three human recipients and in the monkey to three of the test sera. The other three sera gave inconsistent results in man and negative results in monkeys and these differences appeared to correspond with the duration of exposure of the workers. The passive transfer tests did not correlate with the intensity of the prick test reactions in the donors or with the RAST; there was partial correlation with total levels of IgE. Antigen mediated histamine release from whole blood and washed leucocytes from two of the six subjects correlated with the RAST and P-K levels. These findings confirm the presence of specific IgE antibody to the platinum salts, and also of heat stable, short-term sensitising antibodies, presumably STS-IgG.

Adult

Specific IgE antibodies to platinum salts in sensitized workers.

A RAST has been developed for the measurement of IgE antibodies specific to platinum chloride complexes in sensitized workers. Human serum albumin covalently linked to Sepharose beads by the cyanogen bromide method was reacted with ammonium tetrachloroplatinite (II) (NH4)2PtCl4. This conjugate was more suitable for the RAST, than conjugates of HSA and the platinum salt prepared in solution and then linked to the activated Sepharose, showing better sensitivity and giving lower levels of non-specific uptake of IgE from sera of non-exposed subjects with high total levels of IgE, e.g. allergic bronchopulmonary aspergillotics.

Antibody Specificity

Occupational asthma due to inhaled carmine.

Two patients are described with occupational asthma due to carmine, a natural dye extracted from the insect Coccus cactus. Both had dual asthmatic reactons after carmine inhalation. Oral challenge provoked gastrointestinal symptoms in one patient, and asthma in them both, perhaps accounting for their continuing symptoms. One patient worked extracting carmine from the insects and the other used carmine as a cosmetic colouring agent.

Adult

Enzyme linked immunosorbent assay (ELISA) for IgG and IgE antibodies to protein and polysaccharide antigens of Aspergillus fumigatus.

ELISA has emerged as a useful alternative to other more costly and complex tests. Polystyrene microhaemagglutination plates have been used as solid phase to absorb Aspergillus fumigatus protein and polysaccharide components for detection of specific antibodies in patients with various forms of pulmonary aspergillosis. IgG and IgE antibodies to the polysaccharide as well as the protein allergens have been found. For the IgE test a double antibody technique has been developed, which is more sensitive than the conventional indirect ELISA.

Antigens, Fungal

Blood histamine levels after exercise testing.

Histamine has been measured in whole blood and in the plasma of twenty-three subjects following exercise testing of seventeen asthmatics and six normal controls. Whole blood histamine rose in both asthmatics and controls and was associated with a concomitant rise in the basophil count. Plasma histamine in the peripheral venous blood only rose in one patient who developed urticaria after exercise.

Asthma

Isocyanate asthma: respiratory symptoms due to 1,5-naphthylene di-isocyanate.

Occupationally related asthma developing in three patients due specifically to exposure to 1,5-naphthylene di-isocyanate (NDI), a hot curing agent used in manufacturing rubber, has been confirmed for the first time using bronchial provocation testing. This substance has been thought to be safer than toluene di-isocyanate (TDI) and diphenylmethane di-isocyanate (MDI) because of its relatively high melting point (120 degrees C). Each patient worked in the same factory and the circumstances of exposure were similar. Provocation testing was also performed with TDI in concentrations up to 0.018 parts per million (ppm) and MDI in concentrations up to 0.02 ppm, to which the patients had been exposed in the past, but no reactions were elicited. None of the patients had increased bronchial reactivity judged by histamine lability and exercise testing. Each patient was advised to give up his job, but two of the three could not find alternative employment and remained exposed. Three-year follow-up shows that airways narrowing has persisted in those who have remained exposed.

Adult

The effect of sodium cromoglycate, beclomethasone diproprionate and salbutamol on the ventilatory response to cotton dust in mill workers.

A double-blind placebo controlled study of sodium cromoglycate, beclomethasone dipropionate and salbutamol by inhalation was designed to test their effect on respiratory symptoms and changes in ventilatory capacity in cotton mill workers. All three drugs showed some beneficial effect. Salbutamol was the most effective drug studied, in all groups of workers. Beclomethasone dipropionate was also significantly effective particularly in workers with byssinosis or exertional dyspnoea. Sodium cromoglycate was the least effective of the three. Possible mechanisms of action of these drugs are described.

Adult

Respiratory disease in workers exposed to solder flux fumes containing colophony (pine resin).

Twenty-one patients are described who developed asthma, or evidence of a peripheral airways reaction, while working in the electronics industry and exposed to solder flux fumes containing colophony (pine resin). This selected group contained five patients with pre-existing asthma. Fourteen patients had never smoked. Prick-testing with common environmental antigens gave one or more positive reactions in nine patients. The diagnosis was confirmed by occupational-type provocation tests in all workers with colophony-based cored solder, and reproduced by exposure to the fumes of heated colophony alone. Control subjects did not react to the test with colophony. The clinical findings and provocation test reactins have features of a hypersensitivity reaction, although so far specific antibodies have not been found.

Asthma

Effects of orally administered sodium cromoglycate in asthma and urticaria due to foods.

Out of twenty patients with a history of asthma or urticaria attributed to food substances, ten reacted on oral challenge: seven with asthma, one with asthma and urticaria and two with urticaria alone. In five of the eight asthmatic reactors, the symptoms developed within a few sec and there was no associated rise in free venous plasma histamine. In those remaining, two with asthma, two with urticaria and one with both, the symptoms developed only after 20-30 min. A rise in free plasma histamine occurred only in the two subjects with urticaria alone. The third with urticaria and asthma did not have blood estimations performed. Sodium cromoglycate in a dosage of 800 mg a day for 1 week, or a single dose of 1.0 g by mouth, did not block any of the reactions. By inhalation it blocked the asthmatic reactions which developed within a few sec of challenge.

Administration, Oral

Asthma and extrinsic allergic alveolitis due to Merulius lacrymans.

A teacher with breathlessness of insidious onset developed acute symptoms on return home following his discharge from hospital. His flat was found to have extensive dry rot (Merulius lacrymans). Precipitins and specific IgE and IgG antibody against M. lacrymans were present and intracutaneous testing gave a typical dual skin reaction. Pulmonary physiology demonstrated airflow obstruction with a low DLCO and KCO, and a chest X-ray showed diffuse micronodular shadowing, maximal in the mid-zones. Inhalation challenge testing provoked a combined asthmatic reaction without a change in DLCO. Rapid clinical recovery and more gradual radiographic and physiological improvement followed cessation of exposure to the antigen.

Adult