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Biomedical subjects

C J Spry

Publications and source records attributed to C J Spry.

At least 37 records · Page 2Linked to original sources
PubMed1987

Deposits of eosinophil granule proteins in cardiac tissues of patients with eosinophilic endomyocardial disease.

Eosinophilic endomyocardial disease is a complication of the hypereosinophilic syndrome and of several other disorders associated with high blood eosinophil counts. Eosinophil granule proteins may be involved in the development of these lesions. This multi-centre study investigated whether these proteins could be demonstrated within the cardiac tissues of eighteen patients with eosinophilic endomyocardial disease. Serial sections of tissue taken at necropsy or at cardiac biopsy were stained for eosinophil major basic protein by indirect immunofluorescence and for eosinophil cationic protein, eosinophil protein-X, and activated eosinophils by means of alkaline-phosphatase-linked monoclonal antibodies. Activated eosinophils and secreted eosinophil granule proteins were most evident within the necrotic and later stage thrombotic lesions and were found mainly within the areas of acute tissue damage in the endocardium and in the walls of small blood vessels. These findings suggest that eosinophil granule proteins are involved in cardiac injury, producing muscle damage and vascular injury which lead to the development of endomyocardial fibrosis.

Acute Disease↗
PubMed1987

Killing of Plasmodium falciparum by eosinophil secretory products.

The multiplication of two strains of Plasmodium falciparum in culture, as measured by [3H]hypoxanthine incorporation, was inhibited in a dose-dependent manner by granule proteins secreted by purified eosinophils obtained from patients with the hypereosinophilic syndrome. Morphological examination revealed the presence of abnormal parasites inside erythrocytes, indicating that they were killed in situ, and the later stages of the developmental cycle were found to be most susceptible to these toxic effects. A monoclonal antibody against eosinophil cationic protein partially blocked the inhibitory effect, suggesting that it was caused by more than one of the eosinophil granule proteins. Thus some of the antimalarial effects of molecules such as the tumor necrosis factor, which activates eosinophils, may be mediated through the enhanced production of eosinophil secretion products.

Antibodies, Monoclonal↗
PubMed1986

The detection of endothelial cell antigens in cutaneous tissue using methacarn and periodate lysine paraformaldehyde fixation.

The use of monoclonal antibodies with endothelial cell specificity has prompted a search for methods of fixation which combine the morphology of paraffin-embedded tissue, with preservation of labile membrane antigens. Immunohistochemical staining using a variety of endothelial cell markers was compared in tissue fixed in formalin, methacarn, periodate lysine paraformaldehyde (PLP) and in frozen tissue. Whilst lectin-binding with Ulex europaeus agglutinin I (UEA) and localisation of Factor VIII-related antigen (FVIII RA) and laminin was well-visualised in methacarn-fixed and PLP-fixed tissue, fixation in PLP was necessary for the two monoclonal antibodies, PAL-E and EN4. PLP fixation has considerable potential for investigating the histogenesis of vascular tumours, particularly in Kaposi's sarcoma where frozen tissue represents a biological hazard. The normal staining pattern of human dermal vasculature is described in relation to the above endothelial cell antigens.

Acetates↗
PubMed1986

Toxocara canis: interaction of human blood eosinophils with the infective larvae.

This study was carried out to investigate the nature of the immunological responses which took place in a child who had recently recovered from toxocariasis. She had developed a marked eosinophilia and had high titers of toxocara antibodies. Experiments were performed to examine whether Toxocara canis infective larvae could be killed in the presence of her serum and human eosinophils. Eosinophils with human complement, or this patient's serum, adhered to the surface of the larvae within 10 min. By 40 min, using both light and electron microscopy, it was shown that the cells had flattened against the cuticle and degranulated. However, by 3 hr, eosinophils had begun to detach, and the larvae remained alive for at least 1 week afterward. Further addition of serum or of eosinophils, which were shown to be able to immobilize T. spiralis infective larvae, failed to kill the T. canis larvae. It was concluded that, in this patient, the development of an inflammatory response to a T. canis infection was not associated with the appearance of antibodies capable of inducing eosinophil dependent toxicity to the larvae in vitro. Eosinophil dependent killing mechanisms may be less important than other components of the immune response, in immunity to this parasite in humans.

Animals↗
PubMed1986

Chromosome and cell culture studies in eosinophilic leukaemia.

A cytogenetic analysis was carried out on bone marrow cells from 11 patients who presented with hypereosinophilia and the clinical features of the idiopathic hypereosinophilic syndrome. One of these patients was found to have trisomy 8 affecting the myeloid series, including eosinophils. In this patient, marrow eosinophils also showed asynchrony of nuclear-cytoplasmic maturation, and there were increased numbers of myeloid progenitor cells in the blood. Six months later, blast cell transformation occurred, and he died soon afterwards. These findings show that abnormalities in the karyotype of bone marrow cells and culture of blood progenitor cells may help to identity eosinophilic leukaemia among patients who present with features of the idiopathic hypereosinophilic syndrome.

Adolescent↗
PubMed1986

The in vivo cardiotoxic effect of eosinophilic cationic protein in an animal preparation.

We studied the in vivo effects of eosinophilic cationic protein (ECP) on DBA/2 mice, and compared the cardiac lesions caused by ECP with those caused by encephalomyocarditis (EMC) virus. ECP caused myocarditis in two of five mice (40%), and EMC virus did so in five of five mice (100%). Cardiac lesions of ECP were mild and limited to the right ventricular wall, which differed from those in the mice with EMC virus inoculation, where both the right and left ventricles were involved. This experiment is the first demonstration of the in vivo cardiotoxicity of ECP.

Animals↗
PubMed1986

Monoclonal antibodies to human eosinophil plasma membrane antigens enhance the secretion of eosinophil cationic protein.

This study was done to examine the nature of the membrane constituents involved in the secretion of eosinophil cationic protein (ECP) from human blood eosinophils. Three mouse monoclonal antibodies were used, which showed greater binding to membrane antigens on activated, and light density eosinophils from patients with an eosinophilia, than on nonactivated or normal density eosinophils. All three antibodies (EoN4, EoN5 & EoN6) stimulated normal density human eosinophils to secrete ECP, either alone or in association with sepharose-C3b. The antibodies bound to at least two separate sites on the membrane, which were distinct from the receptors for immunoglobulins, C3b, and eosinophil activating factor. One combination of antibodies increased the amount of ECP which was secreted. The membrane antigen recognized by antibody EoN4 was a glycoprotein, molecular weight 75 kD. These findings showed that ECP secretion may be induced by a wider range of stimuli than has been previously recognized, and that the antigens recognized by these monoclonal antibodies may play an important role in the induction of eosinophil degranulation.

Antibodies, Monoclonal↗
PubMed1985

Partial purification and biological properties of an eosinophil-activating factor.

A protein (eosinophil-activating factor, EAF), which enhances the capacity of human peripheral blood eosinophils to kill antibody-coated schistosomula of Schistosoma mansoni, has been partially purified from supernatants of cultured peripheral blood mononuclear cells by sequential chromatography on Sephacryl S200 and DEAE-cellulose. This protein is acidic with a molecular mass on gel filtration of 40 +/- 7 kDa. It not only enhances the activity of eosinophils against schistosomula but also increases their ability to lyse antibody-coated, herpes simplex virus-infected Chang liver cells. It enhances the production of superoxide and hydrogen peroxide by eosinophils that occurs both spontaneously and in response to opsonized zymosan. However, increased respiratory burst activity does not appear to be responsible for the enhancement of eosinophil-mediated killing of schistosomula, since a comparable or greater increase in hydrogen peroxide production is induced by column fractions that have little or no effect on schistosomulum killing. EAF enhances eosinophil degranulation, both spontaneously and after incubation with opsonized zymosan. Enhanced degranulation is associated with release of eosinophil peroxidase and eosinophil cationic protein. These findings suggest that EAF enhances the capacity of eosinophils to kill parasites by increasing the extent of eosinophil degranulation and the amount of toxic granule proteins that are secreted.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1985

The pathogenesis of eosinophilic endomyocardial disease in patients with carcinomas of the lung.

Studies were done on a patient with a carcinoma of the lung induced by hypereosinophilia who was thought to be at risk from developing eosinophilic endomyocardial disease to see whether the development of heart disease could be related to abnormalities in the morphology or kinetics of blood eosinophils. The patient was a 61-year-old man who had a partial resection of a squamous cell bronchial carcinoma of anaplastic large cell type which has spread locally. Seven months later, he developed a blood eosinophil count of 33.9 x 10(9)/1. There were only transient responses to treatment with steroids and tumor irradiation, and he died 15 weeks later. Up to 3 x 10(9)/1 blood eosinophils were degranulated, correlating with serum levels of eosinophil cationic protein. The blood half-life of 111indium-labeled eosinophils was prolonged to 53 h, but their distribution was normal. Although an unsuccessful search was made during life for the development of endomyocardial damage, at postmortem the left ventricle had features of eosinophilic endomyocardial disease in the acute necrotic stage. Among 13 other reported patients with carcinoma of the lung and hypereosinophilia, three also had endomyocardial disease or myocardial lesions. These findings confirm the suggestion that the presence in the blood of greater than 1 x 10(9)/1 degranulated eosinophils can be used to predict the development of eosinophilic endomyocardial disease before it becomes apparent clinically, and they also add weight to the hypothesis that blood eosinophil degranulation causes this complication of hypereosinophilic states.

Blood Proteins↗
PubMed1985

Eosinophilic disorders affecting the myocardium and endocardium: a review.

A wide range of disorders give rise to eosinophil counts greater than 1.5 X 10(9)/l (hypereosinophilia) and cardiac injury. The best known of these is eosinophilic endomyocardial disease (Löffler's endomyocardial fibrosis), which occurs as a major complication of the idiopathic hypereosinophilic syndrome. Here the heart damage appears to be a direct result of tissue injury produced by toxic eosinophil granule proteins within the heart. However, it is not known what causes the eosinophilia in these patients, why the eosinophils degranulate, or why the endocardium is especially susceptible to this type of injury. A number of parasitic infections may give rise to eosinophilic myocarditis. This is usually the result of the presence of the parasites within the myocardium where they die within inflammatory lesions, which may be extensive. Occasionally, drug reactions and rejection of a transplanted heart may produce eosinophilic myocarditis. Allergic granulomatosis and vasculitis (the Churg-Strauss syndrome), which gives rise to granulomas involving the myocardium, and eosinophilic (hypersensitivity) myocarditis usually respond rapidly to treatment with steroids. However, diffuse myocardial involvement may lead to heart failure, and some of these patients may later develop dilated cardiomyopathy. It is concluded that the heart may be affected by a variety of diseases in which eosinophils are a prominent component in the inflammatory cell infiltrates. Eosinophils themselves may contribute to some of the myocardial cell injury which occurs in these diseases, and attempts to limit this with steroids may be worthwhile in some patients.

Cardiomyopathies↗
PubMed1985

Activated eosinophils in familial eosinophilic gastroenteritis.

Two siblings with eosinophilic gastroenteritis who presented with severe iron deficiency anemia and hypoalbuminemia associated with varying degrees of mucosal damage are described. Using a monoclonal antibody to the secreted form of eosinophil cationic protein, we demonstrated activated degranulating eosinophils in the gastrointestinal mucosa that correlated with the degree of histologic damage. This finding suggests that eosinophils may have a primary role in the tissue damage in this condition. Oral disodium cromoglycate (Nalcrom) failed to alter the clinical, radiologic, and histologic abnormalities. Prednisolone, however, was beneficial in 1 case but did not completely reverse the abnormalities.

Adolescent↗
PubMed1985

Eosinophil membrane antigens: phenotypic frequencies in normal individuals and patients with the hypereosinophilic syndrome.

The membrane antigen phenotype of eosinophils from six normal individuals and eight patients with the hypereosinophilic syndrome (HES) were examined to see whether subpopulations of eosinophils exist. Experiments were done with a panel of 6 monoclonal antibodies, using the fluorescent activated cell sorter, and immunocytochemistry. All six antibodies bound eosinophils and neutrophils, but not lymphocytes, monocytes, platelets or erythrocytes. The phenotypic frequencies of five of the six antibodies were increased in patients' eosinophils (p less than 0.005). This increase was associated with the intermediate-density eosinophils, while the antigen detected by antibody Eon 7 was associated with the light-density eosinophils. Normal eosinophils could be induced to increase their expression of these membrane antigens by incubation with mononuclear cell supernatants which are known to increase the cytotoxic capacities of eosinophil, 'activation'. It was concluded that there is a single eosinophil which undergoes post-mitotic differentiation in the blood, leading to activation and degranulation. The heterogeneity seen in patients' eosinophils reflect different stages of cell maturation and activation.

Antibodies, Monoclonal↗
PubMed1985

Tissue localization of human eosinophil cationic proteins in allergic diseases.

Mouse monoclonal antibodies were raised to the storage and secreted forms of eosinophil cationic protein (ECP), and were used to study the presence of activated eosinophils and secreted ECP in the tissues of patients with a variety of allergic diseases. Immunocytochemical localization was shown with alkaline phosphatase-linked second antibodies, and fast-red substrate. Deposition of a red reaction product indicated sites in tissues where eosinophils had become activated, and where secreted ECP was present. Activated eosinophils and secreted ECP were found together in (1) skin lesions of patients with chronic urticaria, (2) gut lesions of patients with eosinophilic gastroenteritis and ulcerative colitis, and (3) tissues containing granulomas in patients with allergic granulomatosis and vasculitis - the Churg and Strauss syndrome. These results show the value of these techniques for determining the sites of eosinophil activation and secretion in allergic diseases. They support the suggestion that ECP may be involved in the development of these tissue lesions.

Blood Proteins↗