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Biomedical subjects

P Venge

Publications and source records attributed to P Venge.

At least 163 records · Page 9Linked to original sources

Hyaluronan and myeloperoxidase in human peritoneal fluid during genital inflammation.

The changes in concentration of hyaluronan (HYA) and myeloperoxidase in peritoneal fluid (PF) were studied during genital intraperitoneal inflammation. PF were collected from 111 women undergoing laparatomy for adhesiolysis and reconstructive surgery of the fallopian tubes, or laparoscopy in search of causes of infertility or low abdominal pain. When the number of leukocytes in the PF had been counted, the fluid samples were centrifuged and the supernatants analyzed for the concentrations of HYA and of myeloperoxidase. During genital inflammation, whether post-operative or postinfectious, leukocytosis and elevated levels of HYA and myeloperoxidase were found in the PF. Concentrations of these substances in the PF may be usable as clinical markers for genital inflammation.

Adult↗

Hyaluronan and myeloperoxidase in human peritoneal fluid during genital inflammation.

The changes in concentration of hyaluronan (HYA) and myeloperoxidase in the peritoneal fluid (PF) were studied during genital intraperitoneal inflammation. PF were collected from 111 women undergoing laparotomy for adhesiolysis and reconstructive surgery of the fallopian tubes or laparoscopy in search of causes of infertility or low abdominal pain. When the number of leukocytes in the PF had been counted, the fluid samples were centrifuged and the supernatants analyzed for the concentrations of HYA and myeloperoxidase. During genital inflammation, whether postoperative or postinfectious, leukocytosis and elevated levels of HYA and myeloperoxidase were found in the PF. Concentrations of these substances in the PF may be usable as clinical markers for genital inflammation.

Adult↗

Patients with renal cancer have a larger proportion of high-density blood monocytes with increased lucigenin-enhanced chemiluminescence.

The production of oxygen metabolites is probably important in cancer cell killing. The production of the superoxide anion, O2-, can be measured by lucigenin-enhanced chemiluminescence (Cl). Previous studies have shown that whole-blood lucigenin-enhanced Cl is increased in cancer patients and that this increase is related to blood monocyte activity. The present investigation confirmed these findings and showed that whole-blood lucigenin-enhanced Cl was elevated in 17 patients with renal cell adenocarcinoma (P < 0.001). The activity of the monocytes was studied more in detail, whereby monocytes were separated into different populations based upon differences in densities, i.e., high-density and low-density monocytes. The cancer patients had a significantly larger proportion of high-density monocytes (P < 0.05) than controls. The lucigenin-enhanced Cl of purified high-density monocytes in controls was significantly higher than that of low-density monocytes (P < 0.01). The authors conclude that the increase in the lucigenin-enhanced Cl of whole blood observed in cancer patients may partly reflect the increased activity of a larger proportion of high-density monocytes in these patients.

Acridines↗

Reduced complement and granulocyte activation with heparin-coated cardiopulmonary bypass.

Plasma concentrations of the complement activation products C3b, iC3b, and C3c; the terminal C5b-9 complement complex; and the granulocyte proteins calprotectin, myeloperoxidase, and lactoferrin were assessed in two groups of patients undergoing aortocoronary bypass procedures. In 10 patients operated on, the bypass circuits were coated by the Carmeda Bio-Active Surface and systemic heparinization was reduced to 1.5 mg/kg; in another 10, the systems were uncoated and the dosage of systemic heparinization was 4 mg/kg. In both groups, significant complement activation was observed after the onset of cardiopulmonary bypass, but the maximum levels of C3b, iC3b, and C3c and the terminal C5b-9 complement complex were significantly lower in the heparin-coated group. In both groups, a significant increase in calprotectin, myeloperoxidase, and lactoferrin release was observed by the end of operation. The maximum myeloperoxidase levels were significantly lower in the heparin-coated group than those in the uncoated group (p = 0.03). There was a correlation of borderline significance between the formation of terminal C5b-9 complement complex and lactoferrin release, as well as between the formation of terminal C5b-9 complement complex and myeloperoxidase release (p = 0.05). The postoperative blood loss did not differ significantly between the two groups. We conclude that coating by end point-attached and functionally active heparin allows a significant reduction in the amount of systemic heparinization, and significantly reduces complement and granulocyte activation.

Aged↗

Releasability of human hypereosinophilic eosinophils is related to the density of the cells.

The activity of eosinophils and neutrophils with respect to the release of granule proteins was studied in 11 patients with the hypereosinophilic syndrome (HES). Granulocytes or purified eosinophils were stimulated with serumopsonized Sephadex particles (C3b-induced release), and the released amounts of eosinophil cationic protein (ECP), eosinophils protein-X (EPX) and myeloperoxidase (MPO) were measured by means of specific radioimmunoassays (RIA). Eosinophils obtained from patients with HES released significantly more ECP (P < 0.002) and EPX (P < 0.01) after 20 min of incubation than cells from the control group. The cellular content of ECP and EPX in eosinophils obtained from the patients with HES was significantly reduced to 50% and 62%, respectively, of the content of these granule proteins of eosinophils from the control group. In separated eosinophils light-density eosinophils released more of both ECP and EPX than normal density eosinophils. There was no difference in MPO release between the patients and the control group. We conclude that the eosinophils from patients with HES have an increased propensity to release their granule proteins and the releasability seems to be related to the density of the cells.

Adolescent↗

The effect of rGM-CSF on neutrophil and eosinophil regeneration after ABMT as monitored by circulating levels of granule proteins.

In order to further evaluate the effects of rGM-CSF on the reconstituting granulopoiesis, plasma and serum levels of myeloperoxidase (MPO) and lactoferrin (LF), as well as serum levels of eosinophil cationic protein (ECP), were monitored daily during a period of 3-4 weeks following ABMT in a group of 22 patients treated with either rGM-CSF (n = 11) or placebo (n = 11). Despite faster increase in the neutrophil counts in the rGM-CSF group, we did not observe any difference either in P-MPO or in P-LF during the period of early engraftment (days 11-19). This finding indicates that the proliferative effect of rGM-CSF on the neutropoiesis may be overestimated when neutrophil counts alone are taken into consideration, and suggests that other mechanisms may have contributed to the increase in the number of circulating neutrophils. The ratio of the serum to plasma level of LF, but not of MPO, was higher in the rGM-CSF group, probably reflecting a specific in vivo neutrophil priming effect. In the rGM-CSF group there was a clear increase of S-ECP during the second and third week post transplant, corresponding to an increase in eosinophil counts, which indicates that rGM-CSF stimulated eosinophil reconstitution without causing excessive activation of the mature eosinophils.

Adolescent↗

Serum levels of granulocyte-colony stimulating factor (G-CSF) in bacterial and viral infections, and in atypical pneumonia.

Serum granulocyte-colony stimulating factor (G-CSF) was measured with an ELISA method in patients with acute bacterial and viral infections, or with an atypical pneumonia. Before initiation of antibiotic treatment, G-CSF was found to be significantly increased (799 +/- 1501 ng/l) in sera from 34 patients with an acute bacterial infection compared with the 27 patients with a viral infection (58 +/- 34 ng/l; P < 0.001) and with the eight patients with an atypical pneumonia (60 +/- 33) ng/l; P < 0.001). No significant difference in G-CSF levels was seen between gram-positive and gram-negative bacterial infections. In septic shock, increased G-CSF levels were seen both in patients with leucocytosis and leucopenia. In uncomplicated bacterial infections, both G-CSF and IL-6 were increased on day 0, and decreased rapidly after initiation of antibacterial therapy and before the patients became afebrile. In bacterial infections on day 0, G-CSF levels correlated with mononuclear cells (rs = -0.62, P < 0.001), IL-6 (rs = 0.40, P < 0.05) and S-MPO (rs = -0.5, P < 0.01). In viral infections, G-CSF was correlated with mononuclear cells (rs = 0.41, P < 0.05), white blood cell counts (rs = 0.56, P < 0.01), neutrophils (rs = 0.41, P < 0.05) and CRP (rs = 0.47, P < 0.05). We conclude that G-CSF is rapidly raised in the blood in acute bacterial infections but not in acute viral infections or in infections with Mycoplasma pneumonia. Our results also support the theory that G-CSF is involved in the mechanisms of mobilization of neutrophils into the peripheral circulation.

Acute Disease↗

Nasal challenge shows pathogenetic relevance of specific IgE serum antibodies for nasal symptoms caused by hexahydrophthalic anhydride.

Hexahydrophthalic anhydride (HHPA) is a component of some epoxy resin systems. A high fraction of HHPA-exposed workers display nasal symptoms, and some of them have specific serum antibodies. To test the pathogenetic relevance of the antibodies nasal challenge tests were performed with a conjugate of HHPA and human serum albumin (HSA) at three increasing concentrations. Eleven subjects, who were IgE-sensitized against HHPA (positive in RAST and in skin-prick test against the HHPA-HSA conjugate), and who reported work-related nasal symptoms, had a significant increase of nasal symptoms and a decrease of nasal inspiratory peak flow after the challenges. The symptoms were associated with specific serum IgE, but with IgG. Further, significant increases were found in eosinophil and neutrophil counts, and in levels of tryptase, and albumin, whereas no clear rise was recorded for eosinophil cationic protein in nasal lavage fluid. Nine subjects, who were not sensitized, but who complained of work-related nasal symptoms, and 11 subjects, who were not sensitized and had no symptoms, displayed no significant change in any of these parameters. It is concluded that the symptoms in some of the workers were caused by an IgE-mediated mast cell degranulation, followed by an inflammatory reaction, engaging eosinophil and neutrophil cells.

Adult↗

Serum eosinophil cationic protein in relation to bronchial asthma in a young Swedish population.

How are the serum concentration of eosinophil cationic protein (S-ECP) and the blood eosinophil count (B-Eos) related to symptoms of asthma, allergy, and bronchial hyperresponsiveness (BHR)? We measured S-ECP, B-Eos, and total and specific IgE in serum in blood samples from 699 randomly selected persons 20-44 years old. They also underwent a structured interview, spirometry, a methacholine provocation test, and skin prick tests as part of the European Community Respiratory Health Survey. B-Eos and S-ECP were found to be closely related to asthma symptom score (P < 0.001), total IgE (P < 0.001), and BHR (P < 0.001). On the basis of the results, the subjects were divided into four groups: healthy controls, patients with allergic rhinitis, patients with nonallergic asthma, and patients with allergic asthma. There were significant differences in both B-Eos and S-ECP among the groups (P < 0.001), the highest values being found in the allergic asthma group. B-Eos and S-ECP each had an additive value in predicting the occurrence of asthma. Among persons with high concentrations of both variables, asthma was eight times more common than in those with low concentrations. Allergy and BHR were also found to be independently related to B-Eos and S-ECP levels. Furthermore, both B-Eos and S-ECP showed good correlation to subjective and objective measures of asthma activity. We conclude that both B-Eos and S-ECP and their interrelationship may be of value in assessing the activity of asthma. However, their role in disease management was not established in this cross-sectional study.

Adult↗

Priming of eosinophil and neutrophil migratory responses by interleukin 3 and interleukin 5.

In the present study the influence of interleukin 3 and interleukin 5 on the migration of normal eosinophil and neutrophil granulocytes has been investigated. LTB4, PAF, f-MLP, C5a and ZAS were used as chemoattractants, and HSA and pooled normal human serum were used as chemokinetic agents. Recombinant human IL-5 (rh-IL5) at a concentration of 4 x 10(-12) mol/l was chemotactic for eosinophils, while recombinant mouse IL-5 (rm-IL5) attracted both eosinophils and neutrophils. IL-3 (rh-IL3) at a concentration around 10(-12) mol/l exerted a priming effect on eosinophil and neutrophil migration, i.e. chemotactic and chemokinetic responses to all agents tested. Human IL-5 at a concentration of 2 to 20 x 10(-12) mol/l primed the chemotactic and chemokinetic responses of eosinophils to all agents tested. The migration of neutrophils was also primed by rh-IL5, but at higher concentrations, i.e. around 10(-10) mol/l. IL-5 of mouse origin primed the migration of both eosinophils and neutrophils. In conclusion, IL-3 primed the migratory function of both eosinophils and neutrophils, while IL-5 was a more potent primer of eosinophil than of neutrophil migration.

Animals↗

Roller and centrifugal pumps compared in vitro with regard to haemolysis, granulocyte and complement activation.

A Biomedicus centrifugal pump and a Polystan roller pump were compared in vitro with regard to differences in haemolysis, granulocyte and complement activation. Six circuits of tubing and oxygenators were connected to each pump. Heparinized fresh human blood was circulated for 72 hours in the systems. Blood samples were drawn at defined intervals. Haemolysis was assessed by determination of lactate dehydrogenase (LD) and potassium, and granulocyte activation by quantification of the granulocyte proteins calprotectin, lactoferrin and myeloperoxidase. Complement activation was assessed by measuring C3 activation products (C3b, iC3b and C3c), and the terminal C5b-9 complement complex (TCC). The results indicate more haemolysis and complement activation in the roller pump group, revealed by significantly higher concentrations of LD, potassium, C3 activation products and TCC. Calprotectin, lactoferrin and myeloperoxidase were all significantly increased in both groups, but the rise appeared earlier in the roller pump group. The concentrations of LD and potassium both correlated significantly with C3 activation products, indicating that complement activation may at least partly be responsible for the haemolysis.

Cell Adhesion Molecules, Neuronal↗

Dexamethasone treatment of infants at risk for chronic lung disease: surfactant components and inflammatory parameters in airway specimens.

The mechanisms explaining the beneficial effects of glucocorticoid in ventilator-dependent preterm infants are not known. In the present randomized trial, we evaluated the hypothesis that dexamethasone (DEX) treatment of small, preterm infants at risk for chronic lung disease favorably affects the surfactant system. Twenty-three ventilator-dependent infants, with a mean +/- SD gestational age of 26 +/- 2 wk and a mean birth weight of 836 +/- 173 g, received 1 wk of treatment with either DEX (dose 0.5 mg/kg/d) or placebo beginning at 2 wk of age. The airway specimens were analyzed for surfactant components, surface activity, surfactant inhibitors, and inflammatory mediators. The concentrations of these parameters in epithelial lining fluid were calculated using the urea method. DEX treatment decreased the concentration of nonsedimentable protein in epithelial lining fluid within 3 d (p < 0.05). The nonsedimentable fraction of airway specimens decreased the surface activity of surfactant as a function of protein concentration. At a constant protein concentration, the protein from placebo-treated infants inhibited the surface activity of human surfactant in vitro more than protein from DEX-treated infants (p < 0.05). DEX transiently increased the concentration of surfactant protein-A in epithelial lining fluid but had no effect on surface activity of the sedimentable surfactant complex or on concentrations of phosphatidylcholine, IL-1 beta, lactoferrin, or myeloperoxidase. We conclude that the acute beneficial effect of DEX treatment in preterm ventilator-dependent infants may in part be mediated through a decrease in the concentration of non-sedimentable protein and a decrease in the capacity of this protein to inhibit surface activity.

Blood Proteins↗

Purification and characterization of a human neutrophil lipocalin (HNL) from the secondary granules of human neutrophils.

A 45 kDa-protein was purified from the granules of human neutrophils. The protein consists of two apparently identical subunits. The isoelectric point was pH 8.40, and the molecular weight 45 kDa (unreduced) or 24 kDa (reduced). Treatment of the protein with Endoglucosidase F resulted in a reduction in the molecular weight to 20 kDa, indicating the presence of N-linked carbohydrate. The extinction coeffient was E1%,1cm = 13.76 at 280 nm. The 60 amino acid sequence revealed up to 65% sequence homology with rat alpha 2-microglobulin-related protein, which belongs to the lipocalin family. The protein co-sedimented with secondary (specific) granule marker proteins and correlated to the neutrophil content of Lactoferrin (r = 0.81, p < 0.001) and was estimated to be 0.59 microgram 10(-6) cells. Release studies showed that the neutrophils released 51.4 +/- 9.0% of the total cellular content of the protein when they were exposed to serum-opsonized particles, which was much higher than the release of Myeloperoxidase (12.7 +/- 3.5%) and Lactoferrin (22.9 +/- 4.7%). The N-terminal and four tryptic fragment amino acid sequence of the protein was identical with an N-formyl peptide binding 24 kDa protein and gelatinase associated protein of human neutrophils. In conclusion, we have purified and characterized a protein, human neutrophil lipocalin (HNL), from the secondary granules of human neutrophils and shown that it is readily mobilized from the neutrophils upon stimulation.

Acute-Phase Proteins↗

The monitoring of inflammation by specific cellular markers.

The use of specific assays for unique secretory components of various inflammatory cells in the clinical evaluation of inflammatory diseases is a new and fascinating possibility, since these assays seem to be more sensitive indicators of inflammatory activity than the conventionally used methods and since these unique cellular markers in addition provide us with useful pathophysiological information. So far the most widely used markers are eosinophil cationic protein (ECP) from the eosinophil and neutrophil markers such as myeloperoxidase and elastase. Serum measurements of the former are used quite extensively in the evaluation of the inflammatory process in the lung of asthmatics whereas the latter predominantly are used in relation to bacterial infections and as compatibility markers in relation to extracorporeal circulation. Recent developments have shown that the serum measurement of a new protein from the neutrophil, human neutrophil lipocalin (HNL), is a superior means to distinguish acute bacterial and viral infections. The future access to a panel of unique cellular markers of inflammatory cells will undoubtedly reveal new exciting possibilities in the diagnosis and therapeutic monitoring of patients with inflammatory diseases.

Eosinophils↗

Biocompatibility of heparin-coated circuits used in cardiopulmonary bypass.

The combined effect of heparin coating of cardiopulmonary bypass (CPB) circuits and reduced dose of systemic heparin on activation of the complement system and blood leukocytes was investigated in 19 patients undergoing coronary bypass surgery and randomly allocated to two groups. A heparin-coated CPB circuit together with a 50% reduction of the standard heparin dose were used for ten patients (HC group), and a standard CPB circuit with a standard heparin dose (300 IU/kg) for nine (C group). Significant rise in the levels of neutrophil-derived myeloperoxidase, lactoferrin and calprotectin were observed during CPB in both groups, but the total accumulated levels were significantly lower in the HC than in the C group (p < 0.05). Complement activation, assessed from levels of C3a and terminal complement complexes was similar in both groups. The lower levels of myeloperoxidase, lactoferrin and calprotectin during CPB in the HC group indicate that surface modification with end-point attached heparin enhances the biocompatibility of CPB.

Biocompatible Materials↗

Serum eosinophilic cationic protein and lactoferrin related to smoking history and lung function.

Some smokers have an accelerated loss of lung function, possibly due to a chronic bronchial inflammation in which granulocytes are involved. Eosinophil cationic protein (ECP) and lactoferrin (LF) are granule proteins in the eosinophil and neutrophil granulocyte, respectively. We wanted to investigate the relationship of serum (s) ECP and LF concentrations to smoking history and lung function alteration. This partly cross-sectional and partly prospective study included 98 nonatopic smokers and 31 lifetime nonsmokers. As participants in a smoking cessation programme, 50 of the 98 smokers ceased smoking for > or = 1 year. Smoking history, lung function and blood samples were obtained at the start of the study, and smokers and ex-smokers also gave blood samples 3, 6 and 12 months later. s-ECP and s-LF were elevated in smokers compared to people who had never smoked. s-ECP was linearly associated with daily cigarette consumption and forced expiratory volume in one second (FEV1) residuals. In a multiple linear regression analysis, low s-ECP and high s-LF were associated with decreased FEV1 residuals. s-ECP and s-LF together accounted for 10.2% of the variation in FEV1 residuals. After smoking cessation, s-ECP and s-LF decreased within 6 months. s-ECP and s-LF are raised in smokers, and may serve as indicators of granulocyte activation. We speculate that they might contribute to prediction of accelerated lung function loss in smokers, but this question needs further investigation in a prospective study.

Blood Proteins↗