Biomedical subjects
C J Spry
Publications and source records attributed to C J Spry.
The pathophysiology of endomyocardial fibrosis.
Explore the source record for details and available documents.
The mechanisms which produce vacuolated and degranulated eosinophils.
Explore the source record for details and available documents.
Increased eosinophil colony formation in agar by haemopoietic cells from patients with the hypereosinophilic syndrome.
Colony formation by granulocyte/macrophage and eosinophilic progenitor cells in the blood and/or bone marrow of four patients with "hypereosinophilic syndrome' (HES) was studied in agar culture. Colony-stimulating activity (CSA) was derived from leucocyte feeder layers (LFL) or from medium conditioned by phytohaemagglutinin-stimulated lymphocytes (LCM). The total numbers of colonies in the patients' blood and marrow were normal. When patients' marrow cells were cultured over LFL, the proportion of colonies that were eosinophilic was greater than normal (mean 21% vs 6%, P less 0.001) and this difference was accentuated when CSA was derived from LCM (mean 53% vs 15%, P less than 0.001). LCM derived from normal subjects and LCM prepared from HES patients had similar effects. In the blood the total number of colonies and the proportion of eosinophilic colonies were similar in patients and controls. The overall pattern of colony formation HES differed distinctly from that observed in a patient with eosinophilic leukaemia reported previously. We conclude that the proportion of eosinophil-committed progenitor cells in the marrow of patients with HES is increased, but we have failed to demonstrate a role for the patient's own lymphocytes in augmenting eosinophil production.
Alterations in blood eosinophil morphology, binding capacity for complexed IgG and kinetics in patients with tropical (filarial) eosinophilia.
As the significance of the eosinophilia which is found in some patients with chronic filarial infections is unknown, blood eosinophils were studied in seven patients with tropical (filarial) eosinophilia who had blood eosinophil counts between 5.2 and 56.6 x 10(9)/l. In six of these patients over 20% of the eosinophils were vacuolated, and degranulated eosinophils were found in the three patients with the most severe illness. In four patients serum eosinophil cationic protein levels were raised, and serial studies in two showed that they returned to normal after treatment with diethylcarbamazine. In addition, an increased proportion of eosinophils in these patients were able to bind to complexed IgG suggesting that they were responding to stimuli in the blood, and in one patient the blood eosinophil half-time clearance was prolonged. Labelled cells were cleared into the spleen, liver and bone marrow. These findings support the hypothesis that in patients with tropical (filarial) eosinophilia, blood eosinophils are induced to release their granule constituents into the circulation. It is suggested that these secretion products may interact with microfilariae, and may give rise to some of the clinical features of chronic filarial infections.
Successful surgical treatment of two patients with eosinophilic endomyocardial disease.
Cardiac surgery to treat severe heart failure was of benefit to two patients with endomyocardial disease and hypereosinophilia-eosinophilic endomyocardial disease. Both patients had severe biventricular fibrosis with mitral and tricuspid regurgitation. One had predominant right ventricular disease and was treated by right ventricular endocardectomy with tricuspid and mitral xenograft valve replacement. The second patient's main haemodynamic problem was considered to be mitral regurgitation. His mitral valve was replaced by a Starr-Edwards prosthesis; endocardectomy was not performed. Though both patients had toxic confusional states for several weeks postoperatively there was distinct symptomatic and objective evidence of improvement which has been maintained for over 16 months. Previous reports of surgical treatment of 22 patients without eosinophilia (all of whom had endomyocardial resection) and three other patients with eosinophilia have shown equally encouraging results. There has been no evidence of recurrence or progression of heart damage in follow-up periods of up to seven years. It is concluded that cardiac surgery is an important advance in the treatment of endomyocardial disease in patients with or without an eosinophilia.
Arrhythmias in patients with hypereosinophilia: a comparison of patients with and without Löffler's endomyocardial disease.
About one third of patients with Löffler's endomyocardial disease have abnormal electrocardiograms and some develop arrhythmias and die suddenly. To assess the significance of these findings, continuous ambulatory ECG monitoring was performed for 48 hr on 6 patients with acute or chronic forms of Löffler's endomyocardial disease, and the types and frequencies of arrhythmias were compared with recordings from 6 other patients with equally high blood eosinophil counts who did not have clinically evident cardiac disease. It was hoped that this would show whether arrhythmias were related to high blood eosinophil counts, cardiac injury or other factors. Three of the patients with endomyocardial disease had multiple ventricular extrasystoles with episodes of ventricular arrhythmias and occasional supraventricular arrhythmias which had not been detected with conventional ECGs. These abnormalities did not occur in 2 of the patients with acute endomyocardial lesions who died, nor were they found in patients who did not have congestive cardiac failure or in the control patients. Rhythm disturbances appeared to be most closely related to the development of cardiac failure and they resolved after successful cardiac surgery. Multiple ventricular extrasystoles and arrhythmias occurring in these patients with Löffler's endomyocardial disease are probably due to metabolic changes in the heart associated with cardiac failure and mechanical changes related to valvular dysfunction rather than a direct effect of the eosinophils themselves on the heart.
Large mononuclear (veiled) cells like 'Ia-like' membrane antigens in human afferent lympn.
Studies were done to see whether large mononuclear cells in human afferent lymph possess cytoplasmic veils or Ia-like antigens on their surface. Small numbers of veiled cells were seen in lymph from five subjects: one with post-phlebitis oedema, one with trophic ulcers of the legs, one with common variable immoglobulin deficiency, and two control subjects. They were not seen in afferent lymph from two other patients with oedema of the legs, and one control subject. Only occasional large mononuclear (veiled) cells formed rosettes with IgG-coated erythrocytes, and they did not attach to glass after overnight culture. They had a distinctive nuclear structure and fluorescent antisera showed that their membranes and veils possessed large amounts of 'Ia-like' antigens. They did not have surface immunoglobulin or a monocyte membrane antigen. It was concluded that the membrane and nuclear structure of human large mononuclear (veiled) cells is in keeping with the possibility that they are derived from Langerhans' cells in the skin, and that they can become interdigitating cells in lymphoid tissues. It is suggested that these cells have an important role in the transport of antigens from the skin and the stimulation of T lymphocytes in lymphoid tissues.
Enzymes altering the binding capacity of human blood eosinophils for IgG antibody-coated erythrocytes (EA).
Blood eosinophils from some patients with an eosinophilia have a higher capacity to bind to IgC antibody-coated red cells (EA) than blood eosinophils from normal people. Twenty per cent of eosinophils from normal blood bound EA, whereas eight of nine patients with hypereosinophilic syndromes and all nine patients with filariasis who were studied had blood eosinophils with EA rosette-forming capacities of between 42 and 89%. High EA binding capacity was reduced in culture, and prednisolone and cytochalasins A and B inhibited normal blood eosinophil EA binding. Normal blood eosinophils developed small increases in EA binding capacity in culture, but marked increases occurred after stimulation with soluble immune complexes, endotoxins and lipid A. Supernatants from granulocytes cultured with zymosan-C3b caused rapid increases in eosinophils EA binding capacity which also occurred with neuraminidase, pronase and trypsin. In vitro alterations in EA rosetting did not require protein synthesis and did not affect eosinophil phagocytic capacity for EA. Substances in culture which did not affect eosinophil EA rosetting capacity included sera from patients with eosinophils with high EA binding capacity and chemotactic substances. Cultured eosinophils also developed an increased capacity to form rosettes with EAC3b, and soluble immune complexes stimulated this further. Conversely, blood eosinophils formed less C3b rosettes when separated from heparinized blood in which C3 activation had occurred. CytochalasinA (but not B) irreversibly inhibited eosinophils EAC3b rosette formation. Trypsin also inhibited, but this effect was reversed within 30 min after washing. It was concluded that eosinophils from normal blood have an intrinsically lwo capacity to bind EA, but that in vivo and in response to stimulation in vitro their ability to bind complexed IgG can approach that seen with blood neutrophils. It is suggested that enzymes in granulocyte secretion products may cause the membrane changes which lead to high eosinophils EA binding capacity. This increase, which can occur separately from alterations in EAC binding or phagocytic capacity, may enable eosinophils to take part more effectively in inflammatory reactions in tissues.
Eosinophilia and allergic reactions to drugs.
Explore the source record for details and available documents.
Hypereosinophilia in rats with Trichinella spiralis infections.
Explore the source record for details and available documents.
Tartrazine sensitivity in renal failure.
Explore the source record for details and available documents.
Strongyloides stercoralis infection and small intestinal lymphoma.
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.
Eosinophils as effector cells in disease.
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.
What eosinophils do.
Explore the source record for details and available documents.
The effects of complement activation by cobra venom factor on the migration of T and B lymphocytes into rat thoracic duct lymph.
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.
Purification of normal human eosinophils using the different binding capacities of blood leucocytes for complexed rabbit IgG.
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.