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Biomedical subjects

P Venge

Publications and source records attributed to P Venge.

At least 289 records · Page 16Linked to original sources

Human eosinophil cationic proteins (ECP and EPX) and their suppressive effects on lymphocyte proliferation.

ECP (eosinophil cationic protein) and EPX (eosinophil protein X) are two highly basic proteins contained in the granules of human eosinophils. In this study, the effect of ECP and EPX upon lymphocyte proliferation in vitro has been investigated. Peripheral blood mononuclear cells from normal donors were cultured in medium containing ECP or EPX at concentrations from 10(-10) to 10(-7) M. 3H-Thymidine incorporation in PHA-blasts or MLR-blasts was dose-dependently inhibited by both ECP and EPX. The effect was irreversible and was not due to cytotoxic damage. The suppressive effect of EPX may involve suppressor cells. The effect of ECP and EPX on lymphocyte proliferation at relevant in vivo concentrations suggests a regulatory role for the eosinophil in immunological reactions.

Blood Proteins↗

Muscle cell leakage of myoglobin after long-term exercise and relation to the individual performances.

Muscle protein release was studied during and after prolonged exercise by means of serum myoglobin determinations. Increased serum myoglobin levels were regularly found after performance of long-term exercise. The correlations (P less than 0.001) to muscle enzymes indicated nonselective release from muscle cells. Myoglobin measured after completed exercise was correlated to the finishing time in a ski race, i.e., the fast skiers showed lower myoglobin levels than slow skiers. Inexperienced skiers and also skiers older than 49 years of age were found to have higher myoglobin levels than the others although the mean finishing times were similar. Myoglobin measured during and after 5 h of bicycle exercise showed large differences even though the relative work load was identical. Myoglobin started to rise 1.2 h (median) after the commencement of the bicycle exercise. The time at which myoglobin started to rise correlated (P less than 0.01) with the myoglobin levels after completed exercise and was not related to the physical fitness of the individuals. The results indicated considerable individual differences with regard to muscle protein leakage during exercise. The leakage is not simply related to the individual's apparent physical fitness but probably also to constitutional factors, such as age and metabolic capacity of the muscle cells.

Adult↗

Ethanol reduces myoglobin release during isokinetic muscle exercise.

Changes in serum myoglobin concentrations were studied in 12 healthy males performing a standardized isokinetic 2-min exercise test. The test was performed on three separate occasions: in the habitual state, during moderate ethanol intoxication and one day after ethanol intake. Although the performed muscle work, maximal heart rate, and blood lactate levels did not differ between the three test occasions, the serum myoglobin increments after exercise were significantly reduced (p less than 0.05) in the ethanol-intoxicated state and also 10-15 hours after ethanol intake. The reduction of the exercise-induced myoglobin increment was not explained by increased elimination of the protein. The mechanism, therefore, is likely to be a reduction of myoglobin release from skeletal muscle due to an ethanol-induced alteration of the muscle cell membrane, possibly by means of adenylate cyclase activation.

Adult↗

The chemokinetic inhibitory factor derived from chronic lymphocytic leukaemia cells. Partial purification and characterization of a new lymphokine.

We have recently described a heat-labile and cell-directed neutrophil migration inhibitory activity that is present in serum from patients with chronic lymphocytic leukaemia (CLL). The inhibitory activity is produced and secreted by CLL cells in vitro. In the present study the inhibitory activity was partially purified from short-term cultures of monoclonal leukaemic B-CLL cells. On gel filtration the calculated molecular weight was apparently 30,000. By anion exchange chromatography, the inhibitory factor was recovered in the fractions that eluted with 0.3 mol/l NaCl. The active material applied to preparative agarose gel electrophoresis migrated towards the anode. The inhibitory factor was totally destroyed by trypsin. In addition it bound to concanavalin A-Sepharose. These properties indicate that the inhibitory factor is a glycoprotein. Antibodies against the isolated inhibitory factor were raised in rabbits. CLL serum was separated by means of gel filtration and the inhibitory activity was recovered in the pool with a molecular weight of approximately 30,000. The activity was completely neutralized by the antibodies raised against the CLL-cell-derived inhibitor, indicating the similarity between this and the serum-derived inhibitor. We have shown the existence of a new lymphokine, derived from B-CLL cells, in serum from patients with CLL.

Cell-Free System↗

Chemotactic activity of LTB4 in man.

An improved skin window chamber technique has been developed and used for a quantitative study of the chemotactic effect of leukotriene B4 (LTB4). LTB4 (0.5 microM) was exposed to a skin window on the forearm of eight healthy volunteers, while phosphate buffered saline served as control in a skin window on the other forearm. Skin window exudates and samples of blood draining the skin window areas were collected after 1, 2, 4, 8, and 24 h. The samples were quantitated for the different types of leukocytes as well as the intra- and extracellular concentration of the eosinophilic cationic protein and lactoferrin as markers of eosinophil and neutrophil granulocytes. A significantly increased migration of neutrophil granulocytes into the skin window chamber containing LTB4 was found from the 2nd to the 8th hour after the initial LTB4 exposure. The eosinophils reached a significant peak at the 4th hour. The rise in the actual number of eosinophil cells did not reach significance, whereas measurements of the eosinophilic cationic protein in the cellular fraction of the exudate exhibited a significant increase as a reflection of the number of eosinophils. This highlights the potential clinical value of eosinophilic cationic protein measurements to reveal eosinophilia instead of the traditional eosinophil counts. Extracellular eosinophilic cationic protein and lactoferrin did not change significantly in the LTB4-exposed skin window, implying that LTB4 does not activate the eosinophils and neutrophils to exocytosis of their enzymes. The present in vivo results support the concept of LTB4 being a potent chemoattractant to neutrophil and less so to eosinophil granulocytes in humans, a chemoattractant that recruits the leukocytes but does not seem to activate them.

Adult↗

Serum levels of lactoferrin and myeloperoxidase in chronic idiopathic and secondary neutropenia. A preliminary report.

In 20 patients with chronic neutropenia, serum lactoferrin (S-LF) and serum myeloperoxidase (S-MPO) levels were assessed. By immunofluorescence, granulocyte-bound immunoglobulins were detected in 12 patients, whereas circulating immune complexes were found in the blood of 8 patients by the 125-I-C1q-binding test (C1q-BT). In both groups of patients, there was a relative increase of S-LF and a relative or sometimes absolute increase of S-MPO. In the latter group, results of the C1q-BT correlated positively with S-MPO but negatively with neutrophil counts. No correlations between S-LF or S-MPO and the results of the granulocyte immunofluorescence test were found. Our results suggest that S-LF and S-MPO levels may be helpful in the further study of patients with chronic neutropenia, to gain more insight into the pathogenetic mechanisms operative in this disease.

Agranulocytosis↗

Bone-marrow regeneration after therapy-induced hypoplasia monitored by serum measurements of lactoferrin, lysozyme and myeloperoxidase.

Serum levels of lactoferrin, lysozyme and myeloperoxidase were measured sequentially after induction treatment in 30 patients with AML in order to test the hypothesis that these proteins may be used to monitor activity and different stages of myelopoiesis in the bone-marrow. The results showed that myeloperoxidase and lysozyme started to rise again 6-8 days after initiation of treatment as compared to 12 d for lactoferrin and 16 d for blood polymorphonuclear leukocytes. The rate of marrow regeneration was exponential and estimated to be 9-20% per d. The comparison between two different chemotherapy regimes showed that the initial reduction in lysozyme, in contrast to other measured variables, was significantly larger with the therapy that contained vincristine and glucocorticosteroids. This might reflect a reduction in lysozyme secretion in addition to the effects on the leukemic cell mass. We conclude that the measurements of lactoferrin, lysozyme and myeloperoxidase in serum under certain circumstances may be used to monitor the myelopoietic activity in the bone-marrow.

Antineoplastic Combined Chemotherapy Protocols↗

Polymorphonuclear neutrophil function and infections following splenectomy in childhood.

22 subjects were controlled 3-23 yr after splenectomy due to childhood trauma (10), idiopathic thrombocytopenic purpura (9) or congenital spherocytosis (3). The control comprised a history of infections, physical examination, routine hematologic values, determinations of serum immunoglobulins, evaluation of complement activities, cultivations from throat and nasopharynx and polymorphonuclear neutrophil (PMN) function tests. 14 patients (63%) had increased susceptibility to recurrent bacterial infections (SBI), most often tonsillitis. All these patients also had abnormal PMN function. The other 8 patients with normal susceptibility to infections showed essentially normal PMN function. There were no differences between these groups with regard to indication for splenectomy, age at splenectomy or the time interval after splenectomy. This abnormal PMN function may explain the raised susceptibility to infections.

Adolescent↗

Ankylosing spondylitis: a chronic inflammatory disease with iron overload in granulocytes and platelets.

The cellular stores of iron in granulocytes and platelets isolated from 29 patients with ankylosing spondylitis were measured by the nuclear microprobe technique. The mean iron content in polymorphonuclear cells (PMNs) was 32 (SD 3) micrograms/g dry weight and in platelets 11 (2.6) micrograms/g dry weight. Corresponding values for age and sex matched healthy controls were 5.2 (1.9) and 4.6 (0.8) micrograms/g (p less than 0.001). Significant correlations were found in the patient group between (PMN) iron and the circulating levels of transferrin, total iron, and lactoferrin (p less than 0.05). PMN iron was not related to serum ferritin. Platelet iron correlated with transferrin (p less than 0.01) but not with the other iron binding proteins. Significant relationships were also found between the PMN iron stores and the inflammatory activity defined by erythrocyte sedimentation rate (ESR) and the immunoglobulins A and G. These data further illustrate the altered iron kinetics in chronic inflammatory disease and record the fact that the redistribution of iron associated with the inflammatory process also includes granulocytes and platelets.

Blood Platelets↗

Patient reactions and granulocyte degranulation during hemodialysis with cuprophane and polycarbonate membranes. A double-blind study.

During dialysis with cuprophane or polycarbonate filters, a fall in neutrophil and eosinophil cell counts is observed. Total complement remains unchanged, but C3a increases indicating complement activation. Release of granular granulocyte proteins is observed indicating granulocyte activation. Patient reactions or biochemical findings indicate no significant difference when polycarbonate or cuprophane membranes are used, except perhaps less complement activation with polycarbonate. The biochemical observations may be due to complement activation or cell contact with the membrane.

Adult↗

Defects in polymorphonuclear neutrophil function and susceptibility to infection in children.

Polymorphonuclear neutrophil (PMN) migration, phagocytosis, chemiluminescence production and chemotactic and chemokinetic activities in serum were investigated in 38 infection-prone children, aged 1 month to 15 years, and in healthy controls. The patients were grouped according to the clinical pattern, that is, into children with mainly upper respiratory tract infections, with frequent middle ear infections, with lower respiratory tract infections and with 'multifocal' infections occasionally accompanied by complications, and according to the severity of the infections. Forty-two defects were found in 28 of the 38 patients examined. Good accordance was found between clinical symptoms and abnormal PMN function. Several of the observed abnormalities are most likely inherited and primary causes of the increased susceptibility, but some of them probably occur as a consequence of the infections. The results indicate that defects in oxidative PMN metabolism and defects in Fc-receptor-dependent phagocytosis are major determinants of susceptibility to infection and that such defects seem to be especially common in patients with severe 'multifocal' infections.

Adolescent↗

Elastase in the different primary granules of the human neutrophil.

Elastase in the human neutrophil is associated with various subpopulations of primary granules of different density. The proportion of this enzyme that is extracted with acetate pH 4.2 and cetyltrimethylammonium bromide varies in the different subpopulations. Nevertheless, the electrophoretic mobility and relative proportions of elastase isoenzymes is the same in both extracts from the different subpopulations. On stimulation of neutrophils with N-formylmethionylleucylphenylalanine, elastase is not released from the least dense subpopulation, whereas other two subpopulations do undergo degranulation to approximately the same extent. However, the release of elastase from these two denser granules differs after they are isolated and treated with calcium.

Cytoplasmic Granules↗

The chemotactic response of granulocytes to the low molecular weight chemoattractants f-MLP, C5f, and LTB4 is dependent on chemokinetic factors.

The dependence of the low molecular weight chemoattractants (LMCs) formylmethionyl-leucylphenylalanine (f-MLP), C5f, and leukotriene B4 (LTB4) on albumin to express their chemotactic activity towards granulocytes (PMNs) was investigated in order to study the required qualities of albumin and if albumin could be replaced by any other proteins. The results demonstrated that the supporting effect of isolated albumin was dependent on the method of purification. Only isolated albumin exposed to ethanol precipitation during the purification procedure supported the chemotactic effect of LMCs. The albumin preparation that supported the effect of LMCs also mediated a chemokinetic effect on PMN migration. Albumin isolated by methods other than ethanol precipitation neither exerted a chemokinetic effect nor supported the chemotactic effect of LMCs. Heated, normal serum and isolated alpha 1-antitrypsin supported the chemotactic activity of LMCs and also mediated a chemokinetic effect on PMN migration. The present investigation suggests an important role for the chemokinetic factors, since it is indicated that their presence is necessary for the chemotactic response of PMNs to the low molecular weight chemoattractants C5f; LTB4, and f-MLP.

Albumins↗

Increased in vivo secretory activity of neutrophil granulocytes in patients with psoriasis and palmoplantar pustulosis.

The relationship between psoriasis and palmoplantar pustulosis (PPP) is uncertain, as is the role of the neutrophil granulocyte in these conditions. In a previous comparative study of the rate of polymorphonuclear leucocyte (PMN) phagocytosis of IgG- and IgG-C3b-coated particles, an increased uptake rate was found in both diseases. Further information on the in vivo activity of PMNs in these conditions may be obtainable by determining the level of lactoferrin (LF) in serum from such patients, since LF serves as a specific marker of the turnover and activity of the circulating pool of neutrophils. In this study on 19 patients with psoriasis and 20 patients with PPP, elevated levels of LF were found in both conditions. In contrast, the levels of lysozyme and beta 2-microglobulin, which are markers of monocyte-macrophage and lymphocyte activity, respectively, were normal. This suggests the selective activation of neutrophils in these disorders. LF was significantly correlated (P less than 0.05 and 0.001, respectively) to the rates of phagocytosis of IgG- and IgG-C3b-coated particles, but not to the chemotaxis of isolated PMNs. There was no correlation between the severity of the disease and the levels of serum LF. The data suggest the increased in vivo activity of neutrophils in psoriasis and PPP.

Adolescent↗

Serum myoglobin concentrations are decreased by beta-adrenergic stimulation.

During infusion with adrenaline in healthy subjects there was a more than 50% reduction in serum myoglobin concentrations. This effect appeared to be specific for beta-adrenergic stimulation, since no changes were seen after prior IV beta-blockade with propranolol, nor did noradrenaline affect the serum myoglobin levels. Oral beta-blockade with propranolol raised the basal serum levels of myoglobin and enhanced the exercise-related rise in serum myoglobin concentrations during ergometer cycling to exhaustion. These observations thus indicate that the beta-adrenergic system affects serum myoglobin concentrations. This should be kept in mind in the evaluation of myoglobin measurements for clinical purposes, and might reflect a physiologically relevant mechanism.

Adrenergic beta-Antagonists↗

The chemokinetic inhibitory factor (CIF) in serum of CLL patients: correlation with infection propensity and disease activity.

We have recently described the partial purification and characterization of a neutrophil migration inhibitory activity present in serum from patients with chronic lymphocytic leukaemia (CLL). This new lymphokine, the chemokinetic inhibitory factor (CIF), is produced by B-CLL cells. It is a heat-labile glycoprotein of an approximate molecular weight (m. w.) of 30000. In this extended investigation 64/89 CLL-patients had CIF in their serum. CLL serum diluted to a concentration of 0.02% gave significantly decreased chemokinetic activity, suggesting that CIF is potent at very low concentrations. 31/89 patients had increased infection propensity. Significantly more patients with CIF in serum had infections compared to the group with normal susceptibility to infections. The combination of low Ig levels and CIF in serum discriminated even better between the infection-prone and non-infection-prone patients. CIF in serum was not correlated to tumour cell mass - estimated by Rai clinical staging - tumour progression or deoxythymidine kinase, S-TK, an enzyme that may reflect proliferating cells. The existence of this new lymphokine in serum seems to contribute to the increased susceptibility to infections seen in CLL patients.

Adult↗

Bronchoalveolar eosinophilia during allergen-induced late asthmatic reactions.

In order to obtain information about the nature of the local inflammatory process during late asthmatic reactions after house dust mite inhalation, bronchoalveolar lavage (BAL) was performed in 19 asthmatic patients and in 5 control subjects. In 16 of the patients and in all of the control subjects, BAL was performed 6 to 7 h after allergen inhalation. Six of the patients showed early and late asthmatic reactions (LAR), 5 showed early reactions, and 5 showed no reactions. Bronchoalveolar lavage was also performed shortly after the early reaction in 5 patients with documented combined early and late reactions. In the BAL fluid of the patients with LAR, a significant eosinophilia (0.01 less than p less than 0.05) was found compared with that in all other patient groups and with that in the control subjects. This bronchoalveolar eosinophilia was accompanied by elevated eosinophil cationic protein/albumin ratio in the BAL fluid (0.01 less than p less than 0.05). These observations suggest that eosinophils and their mediators might be involved in the development of LAR after allergen inhalation.

Adult↗