Tartrazine sensitivity in renal failure.
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Biomedical subjects
Publications and source records attributed to C J Spry.
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A West Indian man who was infected with Strongyloides stercoralis developed small intestinal obstruction. Treatment with thiabendazole did not relieve the obstruction which was found at laparotomy to be due to a poorly differentiated small intestinal lymphoma. There was no blood eosinophilia or accumulation of eosinopohils in the sites of infection. There was no reaction in the skin to delayed hypersensitivity antigens and the blood T lymphocyte count and serum C3 levels were low. From these findings and a review of the literature it was concluded that the immune response in man to Strongyloides stercoralis may depend on T lymphocyte mediated reactions including granuloma formation, and mast cell and eosinophil responses in tissues. We suggest that the association of strongyloides hyperinfection and small bowel lymphoma in this patient may not have been fortuitous. The lymphoma may have led to a reduction in cellular immunity, with the subsequent development of strongyloides hyperinfection.
The ability of eosinophils to express Fc and C3b receptors can alter in vivo and in vitro, and with these membrane receptors eosinophils can bind to IgG or C3b coated metazoan parasites and cells, some of which are killed. In addition, IgG and C3b coated particles can induce eosinophils to secrete their granule contents which include distinct basic (cationic) proteins and peroxidase. These may bind to surfaces or cell membranes where they could initiate complement activation, coagulation or kinin generation. The high incidence of thrombi and endocardial cell damage in patients with persistent eosinophilia (even when it is induced by malignant disease), supports this possibility. Endocardial damage which leads to Löffler's cardiomyopathy may be induced by these products being secreted from circulating eosinophils which have a prolonged blood half-life in hypereosinophilic states. It is concluded that eosinophils have an active role in inducting inflammatory processes in tissues, and that they are important effector cells in some types of parasitic and allergic diseases. Analyses of the way in which these effects occur may show how eosinophils carry out their functions in tissues.
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Experiments were done to see whether C3 or C3-split products are involved in lymphocyte recirculation, with particular reference to B lymphocytes which have C3b receptors. Rats were injected with cobra venom factor (CVF), and the output of subclasses of lymphocytes was measured in thoracic duct lymph in hourly collections during the subsequent 24 h. During the period of acute C3 activation which lasted for 2-8 h, the output of lymphocytes decreased by 47%, but returned to normal at later times, when C3 levels were reduced to less than 20% normal. There was no effect on the output of C3b receptor lymphocytes, and this receptor was not blocked probably because initial C3 levels in lymph were only 13% of blood levels, so that only small amounts of C3b were generated in lymph. When these lymphocytes were labelled and injected i.v. they migrated with the slow rate which is characteristic of normal B lymphocytes. The main effect of CVF was to reduce the output of T lymphocytes by 58% during the phase of acute C3 activation. When normal thoracic duct lymphocytes were labelled and injected, their rate of reappearance in thoracic duct lymph was only reduced during this phase. It was concluded that recirculation of lymphocytes is not C3 dependent, and that insufficient C3b is generated in lymphoid tissues to block C3b receptors on B lymphocytes during periods of rapid C3 activation. However the migratory rate of T lymphocytes through these tissues is reduced during this period, and it is suggested that this may be due to an effect of C3 split products on macrophages which lie along T-lymphocyte traffic routes.
A method has been developed for separating eosinophils from other types of leucocyte in normal individuals. Erythrocytes are sedimented with dextran, and mononuclear cells are removed on an isotonic density gradient of ficoll and sodium diatrizoate. The eosinophils and neutrophils are then washed and sedimented onto plastic petri dishes coated with human IgG and rabbit anti-human IgG antibody; As neutrophils and monocytes have Fc-binding sites for complexed rabbit IgG they attach to the dishes, and the unabsorbed normal eosinophils which lack this binding site are eluted in a purified suspension. The mean purity of the eosinophils obtained in this way was 70%, range 50-90%, and the mean yield was 49%, range 21-81%. This method provides purified eosinophils from normal people without subjecting them to osmotic or plasma membrane stimulation. Normal eosinophils which are prepared in this way are particularly suitable for studying the ways in which eosinophils became altered in disease states.
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Studies were done on blood eosinophils from six patients with a transient eosinophilia, to see whether blood eosinophils were structurally or functionally different from blood eosinophils in eleven normal individuals. It was found that many of the patients' eosinophils were vacuolated, and some contained less specific granules than normal. These eosinophils also possessed Fc receptors for rabbit IgG. When the eosinophil counts returned to normal these abnormalities were no longer found. The nature of these alterations are discussed in relation to the properties of eosinophils in tissues and other types of phagocytic cells responding to stimulae. Suggestions are made about the mechanisms by which they could have come about. It was concluded that blood eosinophils in patients with an eosinophilia may be functionally mature or altered in response to unknown stimulae while they are in the blood.
Studies were done on blood eosinophils from four patients with raised blood eosinophil counts and heart failure. In three of the patients cardiological studies demonstrated the distinctive endocardial lesions and restrictive cardiomyopathy of Löffler's endocarditis and endomyocardial fibrosis. The fourth patient died with similar symptoms and signs. In blood films it was found that all four had more than 1 X 10(9) eosinophils per litre which were vacuolated and contained reduced numbers of crystalloid granules which were also shown to have ultrastructural changes. Unlike eosinophils from normal individuals the patients' eosinophils possessed receptors for rabbit IgG-coated erythrocytes and actively phagocytosed erythrocytes coated with rabbit IgG or human C3b. It is concluded that in these patients, a large proportion of the circulating eosinophils had developed characteristics of mature or stimulated eosinophils. This enabled them to respond to soluble substances in the bloodstream by forming endocytic vacuoles which led to degranulation of the crystalloid granules. These studies, taken in conjunction with other recent work in this field, support the concept that the restrictive cardiomyopathy of hypereosinophilic states, including Löffler's endocarditis and endomyocardial fibrosis, is a result of prolonged release of products from degranulated eosinophils while they are in the circulation.