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Biomedical subjects

P Venge

Publications and source records attributed to P Venge.

At least 307 records · Page 17Linked to original sources

Eosinophils and cellular injury: the Gordon phenomenon as a model.

Three eosinophil proteins, eosinophil cationic protein (ECP), eosinophil protein-X (EPX), and eosinophil-derived neurotoxin (EDN), have neurotoxic properties. EDN and EPX may be identical. ECP is by far the most potent neurotoxic eosinophil-derived protein. The damaging effect of the three proteins have been claimed to be selective. This selectivity can, at least in part, be explained by way of the experimental injections. Several observations are in favour of a selectivity through accumulation. Immunocytochemical localization of intraventricular injected ECP supports this hypothesis and indicates furthermore that ECP has an immediate reactivity towards and possible toxic effect against nervous tissue in general.

Animals↗

Inverse relationship between interferon production by mononuclear leucocytes and oxidative metabolism of neutrophil granulocytes in infection prone children.

The ability of neutrophil granulocytes (PMN) from 15 infection prone children to produce luminol enhanced chemiluminescence (CL) was disturbed to varying extents in eight patients, two of whom were diagnosed as having chronic granulomatous disease (CGD). The ability of peripheral blood mononuclear leucocytes (PBL) to produce interferons (IFN) was normal, as tested with the inducers Sendai virus, E. coli, concanavalin A and L. culinaris lectin. However, the IFN response to the inducer S. aureus Cowan I (SACoI) was decreased in patients with normal CL and tended to be increased in those with decreased CL. There was a significant inverse relation between the CL of PMN and the SACoI-induced IFN responses by PBL of the patients. A regulatory effect of products of oxidative metabolism on SACoI-induced IFN production is therefore suggested. Patients, including those with CGD and controls showed similar basal and in vitro IFN enhanced natural killer (NK) activity of PBL against K-562 erythroleukaemia cells.

Cells, Cultured↗

C3b receptor-mediated phagocytosis in sarcoidosis with extra-thoracic manifestations.

Two groups of sarcoidosis patients were studied. One group of 24 patients had previously had erythema nodosum (EN+), and the other group of 54 patients had never had any such extrathoracic manifestation of the disease (EN-). The two groups were similar with respect to age, disease duration, chest radiographic appearance, and granuloma mass as estimated from the serum concentration of lysozyme. Neutrophil phagocytic function was studied by a kinetic method which allows distinction between Fc- and C3b-receptor-mediated uptake. Fc-receptor function was normal in both groups. The function of C3b receptors was normal in the EN+ groups but significantly reduced in the EN- group. This observation indicates that sarcoidosis associated with erythema nodosum may represent a separate disease entity with respect to the pathogenetic mechanism involved in granuloma formation.

Adult↗

Neutrophil phagocytosis in sarcoidosis. Reduced C3b receptor-mediated phagocytosis in active and silent sarcoidosis.

The phagocytic and complement receptor function of polymorphonuclear neutrophils (PMN) from patients with sarcoidosis was studied using a kinetic assay which allows the distinction to be made between Fc receptor-mediated and C3b receptor-mediated particle uptake. The study included one group (A) of patients with active disease (n = 20), and one group (B) with silent or inactive disease who since 10 years had no symptoms or radiological signs of sarcoidosis (n = 11). Abnormal C3b receptor function was observed in both groups but the impairment was most pronounced in the A group. The presence of C3b receptor dysfunction in both groups with a quantitative difference between the groups, is compatible with C3b receptor dysfunction being a primary causal factor of sarcoidosis.

Adult↗

Human eosinophil peroxidase: purification and characterization.

Human eosinophil peroxidase (EPO) was isolated from granules from granulocytes of a patient with hypereosinophilia. The granules were extracted by means of 0.2 M NaAc, pH 4.0. The purification steps included gel filtration chromatography on Sephadex G-75 superfine and ion-exchange chromatography on CM-Sephadex G-50. The purified protein showed one band on agarose-electrophoresis, a high peroxidase activity, and a 415-nm/280 nm ratio of 1.15. After reduction, EPO showed two bands on SDS-PAGE of m.w. 52,000 and 15,000, respectively. On gel filtration, the unreduced protein had a m.w. of approximately 77,000. Amino acid analyses showed a high content of arginine and aspartic acid. Monospecific antibodies to EPO were prepared in rabbits, and a specific radioimmunoassay was developed. There was an almost linear correlation between the content of EPO measured by the radioimmunoassay and the number of eosinophils in a mixed cell extract from reference material, indicating the eosinophil origin of EPO. The content of EPO was estimated to be 15.0 micrograms/10(6) eosinophils.

Amino Acids↗

The combined action of hyaluronic acid and fibronectin stimulates neutrophil migration.

Previous investigations have demonstrated that the chemotactic response of polymorphonuclear leukocytes (PMN) was stimulated by hyaluronic acid (HA) when serum was present. The aim of the present investigation was to identify the serum factor necessary for the stimulation of PMN chemotaxis by HA. By means of gel filtration, the m.w. of the serum component was shown to be greater than 350,000. Immunoprecipitation of serum with anti-fibronectin, but not with anti-IgM and anti-alpha 2-macroglobulin, inhibited the stimulation of PMN chemotaxis by HA. Preincubation of PMN with HA (10 to 500 micrograms/L) and isolated fibronectin (0.1 to 100 mg/L) significantly stimulated the chemotactic response of PMN. Also, random migration of PMN was significantly increased by preincubation of the cells with HA (10 to 500 micrograms/L) and isolated fibronectin (50 to 200 mg/L). Additionally, PMN preincubated with HA (10 to 50 micrograms/L) and with fibronectin (10 to 50 mg/L) added afterwards, and PMN preincubated with fibronectin (10 mg/L) and with HA (5 to 10 micrograms/L) added after the preincubation, showed a significant stimulation of the chemotactic response. PMN preincubated with serum and chondroitin sulfate, or with fibrinogen and HA, demonstrated no stimulation of the chemotactic response. The present investigation suggests that the combined action of HA and fibronectin, which probably takes place at the cellular membrane, is a major mechanism in the HA-mediated stimulation of PMN migration.

Blood Physiological Phenomena↗

Eosinophil involvement in rheumatoid arthritis as reflected by elevated serum levels of eosinophil cationic protein.

Circulating levels of eosinophil cationic protein (ECP), an eosinophil specific granule protein, and numbers of peripheral eosinophils were determined in 42 patients with rheumatoid arthritis. At the time of the investigation the patients were without drug treatment. They had normal blood counts of eosinophils but on average a five-fold increase of the serum ECP values compared with healthy subjects. The intracellular content of ECP in eosinophils isolated from 14 patients was normal. High serum levels of ECP were particularly observed in patients with a disease of rather short duration but with a more aggressive course. Other factors associated with high ECP values were blood eosinophil counts in the upper normal range, high rheumatoid factor titre and increased inflammatory activity as defined by elevated serum haptoglobin and blood platelet counts. No relation was found between serum ECP and circulating immune complexes or serum total IgE. Synovial fluids obtained from 14 patients with rheumatoid arthritis contained very high concentration of ECP; on average nine times higher than those in the circulation of the patients. During corticosteroid but not NSAID therapy serum ECP decreased on average about 50% compared with pre-treatment values. Although eosinophils are not a notable feature of the synovial membrane infiltrate or cellular joint exudate, data obtained indirectly indicates their participation in the inflammatory reaction in RA.

Anti-Inflammatory Agents↗

Perifolliculitis capitis abscedens et suffodiens (Hoffman). Complete healing associated with oral zinc therapy.

A 24-year-old man with a one-year history of perifolliculitis capitis abscedens et suffodiens (Hoffman) was treated with oral zinc sulfate. Complete healing was seen after three months and the treatment was continued for a total of six months. No relapse has occurred during a five-year follow-up. The mechanisms through which zinc therapy might influence inflammatory conditions are not fully understood.

Administration, Oral↗

Serum-levels of lactoferrin, lysozyme and myeloperoxidase in normal, infection-prone and leukemic children.

Serum levels of lactoferrin, lysozyme and myeloperoxidase have been established in 31 healthy children. On average, serum lactoferrin was 330 micrograms/1, serum lysozyme 1638 micrograms/1 and serum myeloperoxidase 174 micrograms/1. Serum myeloperoxidase was, on average, significantly higher in children than in adults (p = 0.01), whereas serum lactoferrin and serum lysozyme were equal to those of adults. In a group of infection-prone children (n = 31), both serum lactoferrin and serum myeloperoxidase, but not the serum lysozyme levels, were significantly lower (p less than 0.001 and p = 0.002, respectively) than those of the reference children in spite of normal intracellular contents and even somewhat higher peripheral blood polymorphonuclear counts. Based on the assumption that serum lactoferrin and serum myeloperoxidase reflect turnover and activity of neutrophil granulocytes, the findings could suggest reduction in these respects and could be one contributing factor to the high infection propensity of these children. Serum levels of the three proteins have also been measured in 10 children with suspected or various forms of manifest leukemia. It is suggested that the levels reflect turnover and stage of maturation of the myeloid and monocytic cells and could, therefore, aid in the understanding and diagnosis of these diseases.

Adolescent↗

Variations in serum myoglobin after a 2-min isokinetic exercise test and the effects of training.

Serum-myoglobin was measured after the completion of three different types of exercise i.e., dynamic, isometric, and isokinetic. The maximal rises in serum-myoglobin levels were 20%, 70%, and 300%, respectively. On the basis of this finding a 2-min isokinetic test was developed and standardized for the purpose of studying conditions in vivo that may affect myoglobin leakage from skeletal muscle cells. Fourteen healthy men performed the 2-min isokinetic test. Blood lactate increased on average eight times with maximal levels obtained 4 min after completed work. S-Myoglobin levels obtained 4 min after completed work. S-Myoglobin was raised approximately five times after 2 h. The rise in S-myoglobin was significantly (P less than 0.01) related to the loss in muscle strength (torque decline) during the test. After a training period of 3 weeks comprising 4 min of maximal isokinetic exercise three times a week the rise in S-myoglobin after a 2-min isokinetic test was reduced from on average 240 micrograms X 1(-1) to 96 micrograms X 1(-1) (P less than 0.001). The rise in blood lactate was not related to the variations in S-myoglobin or affected by training. The 2-min isokinetic exercise test is an easily standardized exercise test which in combination with measurements of serum-myoglobin should prove valuable in the study of conditions affecting leakage from muscle cells.

Adenosine Triphosphate↗

Schistosoma mansoni: further studies of the interaction between schistosomula and granulocyte-derived cationic proteins in vitro.

Purified eosinophil and neutrophil cationic proteins isolated from the lysosomal secretion granules of human leucocytes have been tested for cytotoxic capacity against lung-stage schistosomula of Schistosoma mansoni in vitro. Eosinophil cationic protein (ECP) caused paralysis but not death at high concentration; this effect was reversible and involved no gross pathological manifestations. Eosinophil protein X (EPX) and neutrophil cationic protein (NCP) were highly toxic at concentrations of 10(-5) mol/l, and induced paralysis at sublethal concentrations. These two proteins exerted their cidal effect principally against the subtegumental musculature and internal tissues of the parasite rather than against the surface syncytium and tegumental outer membrane. ECP and NCP were shown to bind to lung worms at paralysing concentrations, but this binding occurred independently of the charge on the parasite surface. Of several control proteins tested, only protamine was capable of destroying lung-stage parasites; the manifestations of damage were different, however, from those induced by the granulocyte-derived proteins. Parallel assays demonstrated that EPX also possessed cytotoxic capacity against newly transformed schistosomula, but it was less efficient than ECP in this respect. The data are discussed in relation to potential post-skin mechanisms of challenge attrition in the immunized host.

Animals↗

Signs of neutrophil and eosinophil activation in adult respiratory distress syndrome.

Circulating levels of lactoferrin, a specific granule protein of neutrophilic leukocytes, and eosinophil cationic protein (ECP), a specific granule protein of eosinophilic leukocytes, were serially measured in 19 patients at risk for adult respiratory distress syndrome (ARDS). Those patients who developed ARDS had significantly higher concentrations of both proteins than the patients without signs of ARDS. High ECP levels were observed in spite of peripheral eosinopenia. The lactoferrin levels were also increased in relation to circulating numbers of neutrophils. These findings are consistent with an enhanced turnover and/or activity of eosinophils and neutrophils in ARDS and thereby support other clinical and experimental observations suggesting a central pathophysiologic role for granulocytes in ARDS. No relation was found between ARDS or serum concentrations of lactoferrin or ECP and degree of complement consumption, suggesting that other mechanisms besides complement activation may underlie granulocyte activation in ARDS.

Adolescent↗

The value of serum myoglobin determinations in the early diagnosis of acute myocardial infarction.

Myoglobin has been measured in sera from 305 consecutive patients with suspected acute myocardial infarction (AMI) to study the clinical value in relation to other diagnostic methods. On admission the frequency of false negative (i.e. the diagnostic sensitivity) myoglobin values was 28% in the AMI group as compared with 60% for serum creatine kinase (CK) and 46% for serum aspartate aminotransferase (ASAT). Four hours after admission the corresponding figures were 2, 31 and 29%. This makes the diagnostic sensitivity of the myoglobin test 0.98, which is significantly higher (p less than 0.001) than that of the two enzyme tests. The predictive value of a negative myoglobin test was 0.97 and also significantly higher (p less than 0.001 and p less than 0.01) than for CK and ASAT. S-myoglobin was further related to the number of complications and the prognosis of the patients, and high levels appeared to be an unfavourable sign, particularly in combination with an anterior wall infarct. This study has demonstrated and confirmed the superior diagnostic sensitivity of myoglobin determination in early AMI. The inclusion of S-myoglobin in the routine diagnosis of AMI warrants serious consideration.

Adult↗

The chemotactic activity of normal and complement-activated serum as measured by the leading-front method using a Boyden chamber.

The chemotactic activity in serum, defined as the attractant effect of serum on the migration of neutrophil granulocytes (PMN) has been investigated for the purpose of characterizing the major chemotactic factors in serum as measured by the leading-front technique, using a modified Boyden chamber. The chemotactic activity was measured in fresh and heated normal and activated serum and in serum fractions thereof separated by gel filtration. By gel filtration on Sephacryl S-200 a partly heat-labile C3-C5-associated chemotactic factor with molecular weight between 70,000 and 150,000 was isolated from fresh normal serum. The heat-labile chemotactic activity was destroyed by pronounced complement activation. Gel filtration of complement-activated serum on a Sephacryl S-200 column showed the existence of one C5-associated chemotactic factor with approximately 70,000 molecular weight and one unidentified factor with approximately 150,000 molecular weight, whereas no low molecular weight chemotactic activity was demonstrated. On the other hand, gel filtration of activated serum on a Sephadex G-75 column demonstrated one C5-associated chemotactic factor of approximately 70,000 molecular weight and one 10,000-50,000 molecular weight factor active only in the presence of 2% normal serum. This investigation suggests that the chemotactic activity in fresh normal serum is mediated by a partly heat-labile C3-C5-associated complex. In activated serum three chemotactic factors were demonstrated, one unidentified factor with 150,000 mol wt and two C5-dependent factors with 70,000 and 10,000-50,000 mol wt, the latter probably corresponding to C5a desarg. Accordingly, this study also suggests that C5a is not the only chemotactic factor generated in serum.

Blood Physiological Phenomena↗

Eosinophil cationic protein in inflammatory synovial effusions as evidence of eosinophil involvement.

Eosinophils are seldom noted in inflammatory synovial fluids but are reported to infiltrate the synovial tissue in inflammatory arthritides. To elucidate a possible role for eosinophils in inflammatory joint reactions the concentrations of eosinophil cationic protein (ECP)--a specific granule protein from eosinophils--were measured by radioimmunoassay in 90 synovial fluids from patients with various inflammatory arthritides (rheumatoid arthritis, reactive and crystal arthritides, Reiter's disease and psoriatic arthropathy). In the same specimens lactoferrin was measured as an indicator of neutrophil-involved inflammation. In comparison with the normal circulating levels of ECP and lactoferrin the measured synovial fluid concentrations of both proteins were considerably raised in all patient groups with inflammatory joint diseases in contrast to patients with non-inflammatory arthritides. There was a striking positive correlation between the ECP and lactoferrin synovial fluid concentrations. These data indicate that eosinophil activation is prominent in inflammatory joint reactions and is linked to the activation of neutrophils. The regulation of degranulation or secretion by eosinophils is unknown. Our in-vitro studies showed that peripheral blood isolated neutrophils as well as eosinophils degranulated when exposed to IgG complexes. However, eosinophil degranulation was modest compared with neutrophil degranulation. These data suggest that neutrophil phagocytosis of, for example, immune complexes may be one major mechanism in neutrophil degranulation but that other factors determine the appearance of eosinophil products in inflammatory synovial effusions. The possible modulatory or harmful role of eosinophils in inflammatory joint disease can at present only be speculated on.

Adolescent↗

Elevated circulating levels of eosinophil cationic protein in uremia as signs of abnormal eosinophil homeostasis.

Circulating levels of eosinophil cationic protein (ECP), an eosinophil-specific granule protein, and peripheral eosinophils were determined in 56 patients with uremia. The patients were on a chronic hemodialysis or CAPD program or treated with diet only. They had normal counts of peripheral eosinophils but on average a threefold increase of the serum ECP concentrations compared with healthy subjects. The intracellular content of ECP in eosinophils isolated from 6 patients on maintenance hemodialysis was normal. The management or duration of the uremic condition did not influence the circulating ECP levels or eosinophil counts. Neither was any relation found between total IgE levels and peripheral eosinophils or serum ECP. The present results are compatible with an accelerated turnover of peripheral eosinophils in uremia. Such a proposed abnormal eosinophil homeostasis should demand an accelerated marrow eosinophil production, thereby explaining the previously reported marrow eosinophilia in azotemic patients.

Adult↗

Serum-mediated stimulation and inhibition of neutrophil locomotion in sarcoidosis.

Chemotactic and chemokinetic activity was studied in sera from 57 patients with various stages of sarcoidosis. Reduced chemotactic activity was observed in 39% of the sera, mainly in sera from patients with parenchymal densities on chest radiographs. Increased chemokinetic activity was noted in more than one third of the fresh sarcoid sera. Asymptomatic patients showed higher chemokinetic activity in their sera than patients with symptoms. The presence of heat-stable chemokinetic inhibitors was suggested in one third of the cases. No relationship was found between these inhibitors and the inhibitors of neutrophil phagocytosis previously demonstrated in sarcoid sera. Although many of the findings show minor differences to those of normal sera, the liability in sarcoidosis to produce a variety of inhibitors directed against various functions of neutrophils would theoretically hamper the elimination of putative antigens. The presence of serum mediated stimulation and inhibition of neutrophil locomotion could be significant for the pathogenesis of the disease.

Aminopeptidases↗