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Biomedical subjects

P Venge

Publications and source records attributed to P Venge.

390 records · Page 22Linked to original sources

Kinetic studies of phagocytosis. I. The serum independent particle uptake by PMN from patients with rheumatoid arthritis and systemic lupus erythematosus.

The initial phagocytic rate of IgG coated polyvinyl toluene latex particles was assayed for isolated PMN cells. The kinetic studies of phagocytosis were performed in serum-free medium using an electronic particle counter. The mean phagocytic rate for the reference group of apparently healthy individuals was 0.60 min-1. PMN cells from 5 of 26 patients with rheumatoid arthritis (RA) had subnormal values of particle ingestion rate, although the mean of the group was not significantly reduced compared to the controls. Correlation coefficient between the log of rheumatoid factor titer and phagocytic rate was 0.58 (P less than 0.001). During penicillamine treatment an increased rate of phagocytosis was observed in patients with RA. Granulocytes isolated from 17 patients with systemic lupus erythematosus (SLE) had a significantly increased (P less than 0.001) mean initial rate of phagocytosis (0.91 min-u). Two patients in this group had an acute exacerbation of disease activity and were treated with large doses of prednisone. An appreciable decline in phagocytic rate was observed during the intensive corticosteroid therapy.

Adult↗

Monoclonal antibodies distinguish between storage and secreted forms of eosinophil cationic protein.

The toxic effects of eosinophils on parasites and cells are due largely to the secretion of various granule proteins, following stimulation. In order to study this secretory process (degranulation) further, we have raised mouse monoclonal antibodies against both human eosinophil granule extracts and secretion products. From immunocytochemical studies it appears that one antibody, EG1 , recognized both the storage and secreted forms of eosinophilcationic protein (ECP), whereas antibody EG2 only bound to ECP during secretion (and extraction). This antibody also bound to eosinophil protein-X (EP-X). As both antibodies stained eosinophils in formalin-fixed tissues, they were used to demonstrate sites of eosinophil activation and secretion in chronic urticaria. The capacity of monoclonal antibodies to detect differences between storage and secreted forms of proteins is an important property of these reagents with many potential applications in cell biology.

Antibodies, Monoclonal↗

Mechanism of membrane damage mediated by human eosinophil cationic protein.

Recent evidence suggests a role for eosinophil granule proteins in contact-dependent antibody-mediated cytotoxicity. Cytolysis may involve a secretory phenomenon whereby granule proteins are released at the site of contact between eosinophil and target cells. Several basic proteins have been isolated from eosinophil granules, including the major basic protein, eosinophil cationic protein, eosinophil protein-X and eosinophil peroxidase. One of the major granule proteins of human eosinophils is the eosinophil cationic protein (ECP) which has been shown to damage schistosomula of Schistosoma mansoni at concentrations as low as 10(-7). Here, we describe the formation of functional channels by purified human ECP. The transmembrane pores formed by ECP are relatively voltage-insensitive and non-ion-selective, suggesting a role for channel formation by ECP in target cell damage mediated by eosinophils. Channel formation by granule proteins of immune effector cells may represent a general and effective mechanism of target cell killing.

Animals↗

Nasal lavage biomarkers: effects of water damage and microbial growth in an office building.

Selected nasal symptoms were studied in personnel who worked in a damp office building that had microbial growth (including Stachybotrys sp.) in mineral fiber insulation and gypsum board. There were also signs of dampness in the floor. Clinical examinations included nasal lavage and peak expiratory flow measurements in 12 subjects in the damp building; an additional 8 subjects in a control building (i.e., no signs of dampness or microbial growth) were also examined. Hygienic air measurements of microorganisms and volatile organic compounds were performed in both buildings. The concentrations of eosinophil cationic protein, myeloperoxidase, and albumin, and the number of subjects with eosinophils in lavage fluid, were higher among office workers in the damp building than among controls. The damp biiilding had greater amounts of total molds and bacteria in its construction than the building materials in nondamp buildings. In addition, an increase of 2-ethyl-1-hexanol in the indoor air was detected in the damp building-a sign of dampness-related alkaline degradation of diethyl-hexyl phthalate in polyvinyl chloride floor coatings. In conclusion, the results of this study indicate that exposures in a damp office building may cause an inflammatory nasal mucosal response. The results also support conclusions of earlier studies, indicating that building dampness is related to respiratory inflammation.

Adult↗

Influence of two blood conservation techniques (cardiotomy reservoir versus cell-saver) on biocompatibility of the heparin coated cardiopulmonary bypass circuit during coronary revascularization surgery.

Blood conservation during cardiac surgery is critically important because of the inherent risks in homologous blood transfusions. Two techniques for the intraoperative conservation of blood--retransfusion of the red cells using a cell-saver (CS), or retransfusion of the blood using a cardiotomy suction (CTR) system--were compared using biocompatibility markers, granulocyte activation, and production of oxygen-free radicals (OFR). In the CTR group, heparin coated circuits with an uncoated cardiotomy reservoir were used. For the CS group, identical heparin coated cardiopulmonary bypass (CPB) sets, without a cardiotomy reservoir but with a CS, were used. In each group, eight patients had coronary artery bypass grafting performed. The capacity of the whole blood and the granulocytes to produce OFR was estimated by a chemiluminescence, and granulocyte activation was measured as release of the granulocyte granule proteins myeloperoxidase (MPO) and lactoferrin. A significantly reduced capacity to produce OFR by the whole blood was noted at 45 minutes of CPB in the CTR group (68% +/- 17% vs 94% +/- 16% in the CS group). MPO release was higher after 3 hours (p = 0.05) and 20 hours (p < 0.05), postoperatively, in the CTR group (417 +/- 77 micrograms/L and 257 +/- 31 micrograms/L vs 246 +/- 25 micrograms/L and 164 +/- 12 micrograms/L, respectively, in the CS group). We conclude that the heparin coated CPB circuit with the uncoated cardiotomy reservoir may be less biocompatible than the identical CPB set used together with the CS.

Biocompatible Materials↗

Monocytes, but not macrophages, produce the eosinophil cationic protein.

The eosinophil cationic protein (ECP) is a cytotoxic protein with ribonuclease activity, produced and stored in bone marrow eosinophil myelocytes. Mature circulating eosinophils contain about 10 pg ECP per cell. The aim of this study was to investigate the possibility that monocytes produce and store ECP. By results from flow cytometry and specific protein measurement it is shown that human monocytes contain ECP (monocytes about 10 fg ECP per cell). RT-PCR analysis indicated the presence of mRNA coding for ECP in blood monocytes but not in alveolar macrophages. Furthermore, mRNA coding for ECP and low amounts of the protein were found in three myeloid cell lines representing different stages of monocytic differentiation. Differentiation of U-937 cells to macrophages induced lowered transcription of the ECP gene and reduced protein production. Immunohistochemical staining of lung tissue indicated that lung macrophages do not contain ECP. It is concluded that ECP is produced to a low extent by human monocytes and that the production is shut down during macrophage differentiation. This might indicate an alternative transcriptional regulation of the ECP gene in the monocytic lineage compared to the eosinophil lineage.

Antibodies, Monoclonal↗

Lactoferrin, lysozyme, and beta 2-microglobulin in cerebrospinal fluid. Elevated levels in patients with acute cerebrovascular lesions as indices of inflammation.

Serial determinations of beta 2-microglobulin, lactoferrin and lysozyme in CSF were performed in 14 patients with acute cerebrovascular lesions. Marked elevations were noted in patients with cerebral bleeding or hemorrhagic infarction. Patients with infarction without signs of bleeding or with cerebrovascular lesions undetectable by computed tomography also had an increase in these proteins. The increases in CSF of beta 2-microglobulin, lactoferrin and lysozyme could not be explained by a damaged blood-brain barrier but was believed to be a local product of the central nervous system. Peak levels of lactoferrin and lysozyme were noted on day 2-3 after onset of symptoms. Lactoferrin then declined while lysozyme remained elevated for another few days. beta 2-microglobulin gradually increased reaching peak levels on day 4-5 and remained elevated even 2 weeks after the onset of symptoms. We suggest that the increases of lactoferrin, lysozyme and beta 2-microglobulin reflect various inflammatory reactions mediated by granulocytes, macrophages and lymphocytes, respectively.

Acute Disease↗

Eosinophil activity in bronchial asthma.

Eosinophil cationic proteins (ECP), eosinophil protein X (EPX), eosinophil peroxidase (EPO), eosinophil-derived neurotoxin (EDN), and the major basic protein (MBP) have been identified as potent cytotoxic secretory proteins in degranulated eosinophils. Studies of these proteins have clearly indicated a role for eosinophil-derived proteins in inflammatory diseases, including asthmatic inflammation. It has been shown that higher levels of ECP in asthmatics were concomitant with severity of the disease and related to efficacy of treatment of asthma. Proper handling of blood serum for measurement of eosinophil and neutrophil markers including myeloperoxidase (MPO) is essential. Moreover, the time factor in ECP measurement is an important variable because ECP levels differ in chronic stable asthma, during acute exacerbations of asthma, and after allergen challenge. Simultaneous measurements of ECP and MPO may prove to be useful in determining various causes of asthma exacerbations, helping to discriminate between allergic etiologies wherein ECP levels may increase versus infectious etiologies wherein MPO levels may increase. Monitoring the efficacy of anti-inflammatory therapies such as corticosteroids may be enhanced by serial determinations of ECP levels in the blood.

Asthma↗

Effects of drainage in the treatment of acute maxillary sinusitis.

24 patients with maxillary sinusitis were studied with regard to the effect of therapy. 8 of the patients were treated with a single dose of antibiotics and repeated antral aspirations at close intervals. 16 other patients were treated with repeated aspirations only. In the first group, 'cure', in the sense of freedom from retained secretion, was achieved after 3-5 aspirations within 2-10 hours. In the second group, changes in the proteolytic activity and the concentrations of albumin, IgG, IgM and IgA were followed. In purulent secretions the proteolytic activity was high and the concentrations of proteins were low, whereas the proteolytic activity of the serous secretions was low and the concentrations of proteins of the same magnitude as that of the patient serum. As a result of drainage the proteolytic activity was significantly reduced and the concentrations of proteins significantly increased.

Acute Disease↗

Chemotactic properties of retained maxillary sinus secretions.

The chemotactic activity of 82 aspirated maxillary sinus secretions obtained from 32 sinuses in 29 patients was assayed with a modified Boyden chamber technique. The secretions were also analysed with respect to the proteolytic activity according to a modification of a technique described by Moroz. In only 3 of 24 sinus secretions obtained from untreated patients with purulent or mucopurulent sinusitis, but in 5 of 8 serous secretions from untreated patients with serous sinusitis a chemotactic activity exceeding random migration was found. A high proteolytic activity was found to be incompatible with a high chemotactic activity. Regarding mucopurulent and purulent sinusitis, treatment by repeated antral aspiration resulted in an increase of the proportion of chemotactically active secretions and a decrease of the proteolytic activity. Repeated antral aspirations in patients with serous sinusitis resulted in less uniform changes of the chemotactic activity.

Adolescent↗