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Biomedical subjects

C J Spry

Publications and source records attributed to C J Spry.

At least 55 records · Page 3Linked to original sources
PubMed1985

Purification of eosinophil peroxidase and studies of biosynthesis and processing in human marrow cells.

Human eosinophil peroxidase (EPO) was purified from leukocytes obtained from a patient with hypereosinophilia. EPO was extracted from the granule fraction using 0.2 mol/L sodium acetate pH 4.0, and the extract was subjected to gel chromatography on Sephadex G-75 and ion exchange chromatography on Biorex 70. The mol wt calculated from gel chromatography was approximately 50,000. However, under reducing and denaturing conditions, polyacrylamide gel electrophoresis revealed two subunits with mol wt of 50,000 and 15,000. The biosynthesis of EPO was studied in marrow cells from patients with eosinophilia using labeling with (14C)-leucine, followed by immunoprecipitation with anti-EPO, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and fluorography for visualization of labeled EPO. Biosynthesis of an Mr 53,000 subunit was demonstrated. Biosynthetic labeling of the Mr 15,000 subunit was not demonstrated. A labeled Mr 25,000 chain was detected and may represent a degradation product or a chain that, after further modification, produces the Mr 15,000 subunit. Labeling was also detected in two polypeptides with mol wt of 78,000 and 72,000. These forms of EPO seem to represent precursor polypeptides subjected to proteolytic processing in a similar manner as has been reported for myeloperoxidase (MPO). However, Monensin, a proton ionophore, which blocks the processing of MPO, did not inhibit processing of EPO, indicating separate mechanisms by which MPO and EPO are directed to granules.

Antibodies, Monoclonal↗
PubMed1985

Plasma membrane antigens on light density and activated human blood eosinophils.

In order to study the membrane events which lead to human blood eosinophil activation and degranulation, six clone of mouse monoclonal antibodies were made to isolated blood eosinophils from a patient with the hypereosinophilic syndrome (HES). The antibodies were specific for the plasma membranes of blood eosinophils and neutrophils, eosinophil myelocytes and haemopoietic cell lines. A higher proportion of blood eosinophils from eight patients with the HES bound these antibodies compared to normal individuals. Five antibodies stained intermediate density eosinophils preferentially, and one stained the light density eosinophils most strongly. Normal blood eosinophils were induced to express more of these antigens either by culture alone (two antibodies) or culture with monocyte culture supernatant which activates eosinophils for increased cytotoxic capacity (four antibodies). It was concluded that several of the principal antigens on the eosinophil plasma membrane are also present on neutrophils and immature haemopoietic cells, and that their expression in mature blood eosinophils is related to the extent of eosinophil activation and degranulation. It is suggested that these antigens may be useful in studying the ways in which eosinophils alter their plasma membrane during activation and degranulation in vitro, and in the blood of patients with an eosinophilia.

Adult↗
PubMed1984

Deposition of eosinophil cationic protein in granulomas in allergic granulomatosis and vasculitis: the Churg-Strauss syndrome.

Biopsy specimens and tissues obtained at necropsy from two women who died after developing the Churg-Strauss syndrome were analysed to see whether granulomas in these patients contained activated eosinophils or secreted eosinophil cationic proteins, or both. Immunocytochemical studies with monoclonal antibody EG2 showed large amounts of eosinophil cationic protein and eosinophil protein-X (which are toxic for heart cells and other tissues) in the granulomas. Many activated and degranulating eosinophils were seen to be migrating from the blood into these areas. Eosinophils may play a central part in the development of lesions in the heart and other tissues in the Churg-Strauss syndrome.

Adolescent↗
PubMed1983

Selective localization of intravenously injected 111indium-labelled eosinophils in rat tissues infected with Nippostrongylus brasiliensis.

111Indium-oxine-labelled rat eosinophils were injected i.v. into rats infected with Nippostrongylus brasiliensis and controls. Radionuclide imaging was done to measure the rate and extent of radioactive uptake into different regions of the body in vivo. Radioactivity appeared first in the lungs then in the livers and spleens. The distribution of radioactivity and parasites was studied by gamma counting, histology and parasite counts. In infected rats, increased amounts of radioactivity localized in the skin, lungs and small intestines during the dermal, pulmonary and intestinal stages of the disease. It was concluded that localization of radioactivity was closely related to the tissue distribution of migratory larvae and adult worms. This technique may be of value in measuring alterations in eosinophil distribution and tissue localization in vivo, especially in helminthic infections and other disease where many eosinophils accumulate in tissues.

Animals↗
PubMed1983

Infection of inbred and nude (athymic) rats with Brugia spp.

Infective larvae of Brugia pahangi were injected subcutaneously into inbred PVG (-RTIc) rats, and 'nude' (PVG-rnu/rnu) (athymic) rats. Adult worms or circulating microfilariae were recovered from 20/34 (59%) of PVG-RTIc rats and from 30/30 (100%) of 'nude' rats. Fertile worms were regularly found in the lumbar lymphatics and hearts of both strains of rat. Blood eosinophilia first developed in PVG-RTIc rats about 17 days, and in all such animals by 6 weeks. High circulating eosinophil counts persisted only in patent animals, proving a useful hallmark for the presence of microfilariae. Nude rats despite patency, developed eosinophilia only latterly and then to a lesser extent. Specific anti-B. pahangi IgG antibody was first detected at 7 days in all infected PVG-RTIc rats, with levels rising until 8 weeks and remaining high only in microfilaraemic animals; total IgE showed a similar response. Specific IgE rose in all the eight patent rats inconsistently and only to low levels in eight non-patent infected rats. IgG and IgE were undetectable in nude rats. Other strains of inbred rats of different RTI haplotype were also successfully infected with B. pahangi and the human parasite B. malayi, a total of 10/23 (43%) and 5/15 (33%) becoming patent respectively. In the small numbers tested no major influence of RTI haplotype was detected. Infection by the intraperitoneal route did not result in the development of microfilariae. The difference in patency rates between 'nude' and normal PVG rats supports the contention that the development of filarial infections is T lymphocyte dependent. Inbred and 'nude' rats provide a valuable model of human filariasis, in which many features of filarial immunopathology can be studied.

Animals↗
PubMed1983

Echocardiographic features of tropical endomyocardial disease in South India.

Fifteen patients with tropical endomyocardial disease which had been proved angiographically were studied using M-mode and cross-sectional echocardiography to determine the extent to which specific features of this disease could be recognised by these non-invasive methods. Tethering of the posterior mitral valve leaflet to the ventricular wall in combination with areas of echo-dense material in the posterior left ventricular wall and associated papillary muscle appeared to be a constant diagnostic feature of this disease. Colour coding of regional echo amplitude showed high intensity echoes in a distribution corresponding closely to that of the fibrosis known to occur in this condition. Though M-mode echocardiography did not contribute diagnostic information, it was useful in defining the functional consequences of myocardial or mitral valve disease. Digitisation of records allowed a restrictive pattern of left ventricular filling to be observed. It was concluded that cross-sectional echocardiography, particularly when supplemented by colour coded amplitude processing, can make a confident non-invasive diagnosis of tropical endomyocardial disease and so could be useful in assessing its progression or response to treatment.

Adolescent↗
PubMed1983

The cardiotoxicity of eosinophils.

Although an association between high blood eosinophil counts and endomyocardial disease has been known for nearly a hundred years, the reasons for this were not understood. Brockington, Luzzatto and Osunkoya (1970) suggested that eosinophil leucocytes, in susceptible persons, by some unknown mechanisms, cause endomyocardial damage. Evidence to support this possibility has come from three sources: (1) Clinical studies have shown that very high blood eosinophil counts, from any cause, can be associated with endomyocardial disease, and in some patients it has been possible to show that eosinophilia preceded the onset of heart disease. (2) The development of heart disease has been associated with the presence of degranulated eosinophils in the blood and tissues, including damaged endomyocardium, and raised serum levels of eosinophil granule basic proteins have been found in many of these patients. (3) Low concentrations of eosinophil secretion products (which contain these eosinophil granule basic proteins) have been found to injure isolated heart cells in vitro. Studies with purified eosinophil granule basic proteins have shown that cardiac cell damage is the result of a specific toxic effect of eosinophil cationic protein on the plasma membrane and two enzyme complexes (pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase) involved in mitochondrial respiration. These results support the suggestion that under certain conditions, eosinophils may damage the heart, leading to endomyocardial disease, and they offer new approaches for the early diagnosis and treatment of endomyocardial disease both in temperate and tropical countries.

Animals↗
PubMed1983

A comparison of the clinical and cardiological features of endomyocardial disease in temperate and tropical regions.

This study was designed to compare the clinical and cardiological features of endomyocardial disease in temperate and tropical regions. Eleven patients were studied in the U.K., 47 in India and 8 in Brazil. The patients in the U.K. were older, with a male predominance, and they had a systemic illness: the hypereosinophilic syndrome. Half of these patients presented in the early necrotic stage of the disease, and all had biventricular involvement. On the other hand, patients in the tropical countries were younger, with an equal sex incidence, and were from poor, malnourished communities with heavy parasite loads, especially filariasis in India. None presented in the early necrotic stage of the disease and a quarter had isolated right or left ventricular disease. In order to account for these differences between patients in temperate and tropical regions with endomyocardial disease, it was proposed that the nature of the underlying disease and the rate at which endomyocardial lesions develop, determine the clinical features of this disorder. In temperate climates eosinophil granule toxins may produce a rapidly progressive form of the disease in patients with the hypereosinophilic syndrome, whereas the disease may take longer to develop in patients in tropical climates, who have a less marked eosinophilia due to parasitic infections.

Adolescent↗
PubMed1983

A vascular endothelial cell antigen with restricted distribution in human foetal, adult and malignant tissues.

Human vascular endothelial cells were isolated by collagenase digestion of umbilical veins. Hybridomas secreting monoclonal antibodies were raised by fusing a mouse myeloma cell line to spleen cells from mice immunized with the isolated endothelial cells. A clone was selected which produced an antibody binding strongly to human umbilical vein endothelial cells. This antibody, EN 3, was shown to be directed against a major antigen on the surface of the cells, and appeared to be distinct from other antigens previously described on vascular tissues. The antibody bound to a lesser extent to umbilical artery endothelial cells and syncytiotrophoblast. Capillary endothelial cells in adult oesophageal tissues and tonsil were also labelled by the antibody, as were capillaries in a seminoma and infiltrating duct carcinoma of the breast. This well defined distribution in some foetal, adult and malignant tissues suggests that there is structural heterogeneity amongst endothelial cells in different sites, which may be linked to differences in differentiation or function.

Adult↗
PubMed1983

Clinical features of fifteen patients with the hypereosinophilic syndrome.

Fifteen patients with the hypereosinophilic syndrome were studied during a period of 6.5 years. The mean age at onset was 36 years. Two were female. The commonest presenting symptoms were nocturnal sweating with or without severe coughing attacks, symptoms of cardiovascular disease, anorexia and weight loss, neurological and gastrointestinal symptoms and itching with or without skin lesions. The mean blood eosinophil counts at presentation were 20.1 X 10(9)/l. Eight patients had previous allergic or parasitic disease which could have predisposed them to the development of hypereosinophilia. Eight patients had raised serum immunoglobulin levels: IgM in five, IgE in four and IgG in one. Five of nine patients had raised serum eosinophil cationic protein levels. Episodes of clinical relapse occurred with increased white blood counts and were treated with prednisolone and cytotoxic drugs. Thrombotic and embolic complications developed in 10 patients, despite treatment with anticoagulants and inhibitors of platelet function, and were the cause of death in three. Two patients with severe endomyocardial fibrosis responded well to cardiac surgery, and a third required emergency mitral valve replacement. The 12 surviving patients have lived 0.8-11.5 years (mean 4.4), since the onset of their illness. It is concluded that the hypereosinophilic syndrome has distinctive features with an episodic course. The principal complications affect the cardiovascular system, especially endomyocardial fibrosis and thromboembolic occlusion of large and small blood vessels in many organs. Although treatment is usually effective in overcoming relapses, the underlying disease process appears to be unaffected. Despite this, patients can have prolonged periods of remission and may survive for many years.

Adolescent↗
PubMed1983

Cardiovascular features of 11 patients with eosinophilic endomyocardial disease.

This report describes the clinical features, cardiac investigations and treatment of eleven patients with biventricular eosinophilic endomyocardial disease, who were followed up for a mean of 3.2 years. Three patients died. Five patients presented with heart disease and hypereosinophilia. Six other patients presented with hypereosinophilia and developed cardiac disease later. Histological studies showed early acute necrotic lesions in five patients, later thrombotic lesions in one and late fibrotic lesions in three patients. Endomyocardial biopsy was the method of choice for diagnosing early acute necrotic and thrombotic lesions. Late fibrotic lesions were best shown by amplitude processed 2D echocardiography and angiocardiography. Episodes of heart failure responded well to treatment with prednisolone which appeared to inhibit progression of heart disease in two patients. Three patients with severe ventricular disease and valvular regurgitation responded well to surgical treatment. This longitudinal study has shown that eosinophilic endomyocardial disease can now be investigated and treated effectively at each stage from early sub-clinical lesions to late incapacitating endomyocardial fibrosis.

Adult↗
PubMed1982

Toxic effects of human eosinophil products on isolated rat heart cells in vitro.

Rat heart cells and mitochondria were incubated with supernatants from eosinophils or neutrophils that had been stimulated with zymosan-C3b. Supernatants from eosinophils, but not neutrophils, were toxic to rat heart cells in a dose-dependent manner. This was associated with an increased O2 uptake, which was blocked by either 1 mM-cyanide or 100 microM-ouabain. Supernatants from eosinophils, but not neutrophils, caused a decrease in O2 uptake by rat heart mitochondria utilizing pyruvate (+ malate) but not other substrates. The activity of pyruvate dehydrogenase (EC 1.2.4.1) from rat heart was inhibited by Ca2+-free eosinophil supernatants. The activity of oxoglutarate dehydrogenase (EC 1.2.4.2) was also inhibited but not that of lipoamide dehydrogenase (EC 1.6.4.3). Prior incubation with heparin prevented these effects of eosinophil supernatants on heart cells, suggesting that they were caused by eosinophil cationic proteins. Other cationic proteins, including poly-L-lysine and poly-L-arginine were also toxic to rat heart cells, but these reduced O2 uptake. It was concluded that granulocyte secretion products containing eosinophil cationic proteins are toxic to isolated rat heart cells in vitro. This may be due to an initial increase in membrane permeability, which may lead to activation of (Na+ + K+)-dependent ATPase and increased O2 uptake. A second step may involve inhibition of pyruvate dehydrogenase by the same products, leading to a decreased O2 uptake. It is suggested that these mechanisms could contribute to the development of cardiac injury and myocardial disease in clinical situations where many degranulated eosinophils are present.

Animals↗
PubMed1982

Ophthalmologic abnormalities in the hypereosinophilic syndrome.

Twelve patients with hypereosinophilic syndrome were studied to determine the frequency and type of eye involvement in this systemic disease. Four patients (33%) had visual symptoms, including blurred vision in one or both eyes, and one patient had an episode of complete blindness following cardiac surgery. Five patients (42%) had eye involvement by direct examination, and ten (83%) in fluorescent retinal angiograms. The principal defects noted were occlusions of major retinal vessels, choroidal infarct, and patchy or delayed choroidal filling. As these defects all occurred in patients with other severe systemic complications of the hypereosinophilic syndrome, including cardiologic disease, it is suggested that these lesions were the result of thromboembolic disease and that these patients should receive long-term anticoagulation. It was concluded that eye involvement is a frequent and important feature of the hypereosinophilic syndrome.

Adult↗
PubMed1982

Echocardiographic features of eosinophilic endomyocardial disease.

Nine patients with eosinophilic endomyocardial disease who had undergone angiocardiography with histological staging of their disease, were studied by M-mode and two dimensional echocardiography to determine the extent to which specific features of the disease could be evaluated by these non-invasive methods. In seven patients, amplitude processed two dimensional echocardiography showed regions where the relative intensity of endomyocardial echoes was greater than normal, and their distribution corresponded to known areas of fibrosis. Standard two dimensional echocardiography was normal in all but three patients. In eight patients M-mode echocardiography showed only non-specific abnormalities, but appeared to be useful in assessing the functional consequences of myocardial or mitral valve disease. After digitisation a reduction in the duration and an increase in the peak rate of dimension increase during filling was prolonged. It was concluded that amplitude processed two dimensional echocardiography might be useful in diagnosing the extent and severity of endomyocardial disease in patients with hyperosinophilia. These noninvasive techniques may thus provide a means for the early diagnosis of endomyocardial fibrosis and could be useful in assessing in progression or response to treatment.

Adult↗