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Biomedical subjects

P Venge

Publications and source records attributed to P Venge.

At least 217 records · Page 12Linked to original sources
PubMed1991

Eosinophilic cationic protein (ECP) in skin disorders.

Eosinophil cationic protein (ECP) is exclusively secreted only by the eosinophilic leukocyte. In this study the ECP concentration in the serum was measured in patients (n = 155) with various skin disorders and compared with the number of circulating eosinophils. The presence of activated eosinophils in the skin was also studied immunohistochemically using the monoclonal antibody EG-2, which recognizes both the eosinophil protein X (EPX/EDN) and ECP. EG-2 distinctly revealed these proteins in the eosinophils and their granules. Non-activated eosinophils were studied with the monoclonal antibody EG-1. In most cases this did not disclose any more eosinophils and often it was located more diffusely and not seldom on collagen fibers. Elevated serum ECP but normal numbers of circulating eosinophils were found in half of the patients with progressive plaque psoriasis and long-standing daily chronic urticaria. In patients with prurigo nodularis, papular erythematous eruptions, vasculitis, purpura and toxic drug reactions, Wells' syndrome, porphyria cutanea tarda and persistent light reaction the serum ECP was increased, although in some cases the number of circulating eosinophils was normal. In these disorders an increased number of activated eosinophils was found in the skin. Both serum ECP and the number of activated eosinophils normalized when the patients' condition improved. In atopic dermatitis the serum ECP and the number of activated eosinophils in the skin were increased only during exacerbation of the disease. High serum levels of ECP and activated eosinophils in the skin are frequent findings in many skin disorders in spite of often normal blood eosinophil counts.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1991

Neutrophil function in chronic bronchitis.

This study was initiated with the question: Do defects in neutrophil functions predispose patients with chronic bronchitis to their recurrent bacterial infections? Forty five patients with chronic bronchitis and recurrent bacterial infections were studied. A number of aspects of neutrophil functions reflecting migratory and phagocytic functions and oxidative metabolism were measured in vitro, once in all 45 patients and 3 times in 22 patients over a period of 6 months. A great number of abnormalities was found on the first occasion with a complete normalization for all variables except one at the end of the observation period. The number of infectious exacerbations was significantly higher (p less than 0.05) at the start of the observation period i.e. October-November, as compared to the end, i.e. April-May. The oxidative metabolism, as reflected by lucigenin-enhanced chemiluminescence, was significantly reduced (p less than 0.001) also at the period of few infections, suggesting a primary defect of the neutrophil. Smoking was shown to adversely affect luminol-enhanced chemiluminescence and the chemokinetic activity of the patients' cells. We conclude that most variables were altered in a way which was anticipated from the study of individuals with acute bacterial infections. The probable primary defect in oxidative metabolism of the neutrophils in addition to the acquired defects as a consequence of smoking may add to the predisposition of some individuals to their recurrent bacterial infections.

Adult↗
PubMed1990

Eosinophilic inflammation in asthma.

BACKGROUND AND METHODS: The importance of eosinophils in the pathogenesis of bronchial asthma is not established. In an attempt to evaluate the role of eosinophilic inflammation in asthma, we compared 10 normal subjects with 43 patients with chronic asthma, 19 of whom had severe disease as assessed by a clinical scoring method described by Aas and by pulmonary-function tests. Eosinophils were counted in peripheral blood and bronchoalveolar-lavage fluid, and in biopsy specimens obtained from the patients and post mortem from 8 subjects without asthma, but not from the 10 normal controls. Eosinophil cationic protein was titrated by radioimmunoassay in the bronchoalveolar-lavage fluid from all subjects and studied by immunohistochemistry in the biopsy specimens. RESULTS: There was a significant increase in the number of peripheral-blood eosinophils in the patients that was correlated with the clinical severity of asthma (P less than 0.001) and pulmonary function (P less than 0.03). Levels of eosinophils and eosinophil cationic protein were increased in the bronchoalveolar-lavage fluid from the patients and were also correlated with the severity of asthma (P less than 0.001 and P less than 0.002, respectively). Hematoxylin-eosin staining of bronchial-biopsy specimens showed that intraepithelial eosinophils were present only in patients with asthma. Immunohistochemical analysis of eosinophil cationic protein revealed that normal subjects had only a few nondegranulated eosinophils deep in the submucosa, whereas all the patients had degranulated eosinophils beneath the basement membrane and among epithelial cells. In some patients there was a relation between the presence of degranulated eosinophils and epithelial damage. CONCLUSIONS: Eosinophilic inflammation of the airways is correlated with the severity of asthma. These cells are likely to play a part in the epithelial damage seen in this disease.

Adult↗
PubMed1990

Inhibition of neutrophil and eosinophil chemotactic responses to PAF by the PAF-antagonists WEB-2086, L-652,731, and SRI-63441.

The influence of the three PAF-antagonists WEB-2086, L-652,731, and SRI-63441 on the chemotactic response of neutrophil and eosinophil granulocytes to PAF was investigated. When the PAF-antagonists were added to the cell suspension that was exposed to a gradient of PAF, WEB-2086 and SRI-63441 at the concentration of 10(-6) mol/litre inhibited (P less than .01) the neutrophil and eosinophil chemotactic response to 10(-8) and 10(-9) mol PAF per litre; at the concentration of 5 x 10(-6) mol/litre, WEB-2086 and SRI-63441 also inhibited (P less than .02) the response to 10(-7) mol PAF per litre. Under the same conditions L-652,731 at the concentration of 5 x 10(-6) mol/litre inhibited (P less than .01) the eosinophil chemotactic response to 10(-8) and 10(-9) mol PAF per litre. The inhibition of the chemotactic response to PAF by the three PAF-antagonists was specific, since the chemotactic response to C5f, f-MLP, and LTB4 was not affected by WEB-2086, L-652,731, or SRI-63441, neither was the chemokinetic migration induced by albumin.

Azepines↗
PubMed1990

Indices of inflammatory activity in CB and COAD. Phagocyte secretion and chemotaxis.

The monitoring of inflammatory activity in the lungs of patients with chronic obstructive airways disease may be accomplished by the measurement of specific markers of inflammatory cell activity such as the eosinophil cationic protein and the neutrophil-derived myeloperoxidase. However, no specific marker, which reflects the activity of the alveolar macrophage, is available. Eosinophil and neutrophil chemotactic activity may be detected in broncho-alveolar fluid as a sign of macrophage activity. We report preliminary data, which indicate that both chemotactic activities are elevated in patients with chronic bronchitis. The predominant activities elute at a molecular weight of about 10 kDa but also at a position after the total volume of the column. We conclude that secretory products from inflammatory cells may be measured in broncho-alveolar fluid from patients with chronic bronchitis. Whether such measurements will prove useful in relation to therapeutic trials in these patients is not known but is most likely.

Bronchitis↗
PubMed1990

A critical look at blood samples in CB and COAD.

Few studies have utilized measurements of blood variables to estimate the clinical activity of chronic bronchitis in relation to clinical trials. In one study, we have followed such patients with repeated measurements of serum levels of lactoferrin, myeloperoxidase and lysozyme as markers of neutrophil and monocyte/macrophage activity. We showed that these patients have raised lysozyme levels, as signs of ongoing activation of the macrophage population, irrespective of the presence of infectious exacerbations. Lactoferrin and myeloperoxidase levels, on the other hand, showed large variations with peaks mostly coinciding with the infectious exacerbations. In another study, we made repeated measurements during a 6-months' period of a number of neutrophil activities. These data showed increased activities with respect to migration and oxidative metabolism during the period of increased numbers of infectious exacerbations. All but one variable became normal during periods of few infectious. Thus, the lucigenin-enhanced chemiluminescence was subnormal during this period suggesting an abnormality of neutrophil oxidative metabolism in patients with chronic bronchitis. We conclude that the monitoring of markers of inflammatory cell activity in serum may be useful as indicators of the clinical activity of chronic bronchitis and that the measurement of functional activities of the neutrophil is dependent on seasonal variations in the exposure to infectious agents in the community.

Biomarkers↗
PubMed1990

Myeloperoxidase in human lung lavage. I. A marker of local neutrophil activity.

The origin of myeloperoxidase (MPO) in bronchoalveolar lavage (BAL) was investigated in the first part of the study. Radioimmunoassay of the cellular and supernatant MPO content as well as the peroxidase-antiperoxidase (PAP) technique were employed to determine the cellular source of MPO. The concentrations of MPO were measured in serum and BAL in the second part of the study. The aim was to determine whether the capillary bed was also a source of MPO. Neutrophil numbers in BALs obtained from 20 healthy subjects correlated significantly to the concentrations of MPO in cell-free BAL supernatants (r = 0.643, P less than or equal to 0.01). The cellular content of MPO in mixed BAL cells was significantly correlated to the number of neutrophils in the mixture (r = 0.536, P less than 0.05), but not to the number of any other cells. Moreover, the PAP-technique identified MPO in lung tissue neutrophils in resection specimens obtained from three patients undergoing surgery. This technique also revealed strong MPO activity in all BAL neutrophils and a weak activity in merely 4% of the alveolar macrophages in cytospin preparations obtained from seven BALs. High BAL/serum ratio of MPO concentrations suggests that MPO is of local origin, rather than passively diffused from the circulating pool. We therefore conclude that strong evidence suggests that MPO in BAL originates from lung neutrophils and that BAL MPO content may be used to estimate the neutrophil presence or activation in epithelium lining fluid.

Adult↗
PubMed1990

Myeloperoxidase in human lung lavage. II. Internalization of myeloperoxidase by alveolar macrophages.

Bronchial wash and bronchoalveolar lavage were performed in 12 healthy subjects (five smokers), in order to elucidate whether or not material of neutrophil origin may be phagocytized by lung macrophages in vivo. Cells from different levels in the bronchial tree were obtained by sequential injection and subsequent aspiration of either four 50-ml or five 10-ml aliquots. Each aliquot was used for the determination of total and differential cell counts. The proportion of myeloperoxidase-positive alveolar macrophages was determined by specific immune histochemical staining. The percentage of myeloperoxidase-positive macrophages was highest (median 94.8%, range 37-98.5%) in the 10-ml aliquots and lowest in the last three 50-ml aliquots (median values 1-2.5%) (P less than 0.001). A significant correlation was obtained between the fraction of myeloperoxidase-positive macrophages and the percentage count of bronchoalveolar lavage neutrophils (r = 0.466, P less than 0.05). Furthermore, the cellular myeloperoxidase showed a significant inverse correlation (r = -0.46, P less than 0.05) to the viability of the bronchoalveolar lavage cells. Our findings are compatible with previous demonstrations in animals of neutrophil phagocytosis by lung macrophages and show that this phenomenon in particular occurs in the more proximal airways. The internalization of neutrophils or neutrophil components by airway macrophages may be an important scavenger mechanism for protection of the lung from the deleterious effects of activated neutrophils.

Adult↗
PubMed1990

The human eosinophil in inflammation.

Active research during recent years has clearly shown that the eosinophil is a potent inflammatory cell taking active part in almost all kinds of inflammatory processes. The activity of the human eosinophil is mediated by the secretion of four well characterized cytotoxic proteins, ECP, EPO, EPX/EDN and MBP in addition to lipid mediators such as LTC4 and PAF and toxic oxygen metabolites. The cytotoxic potential of the eosinophil has been demonstrated in a number of diseases with a close association of eosinophil accumulation with secretion of granule proteins and tissue injury. Also the measurements of the proteins in various body fluids have provided evidence for the active participation of eosinophils in a number of diseases such as asthma, ulcerative colitis, rheumatoid arthritis, psoriasis to mention a few. The identification of the principles that attract eosinophils to the sites of inflammation must be a major goal in our attempts to control the activity of this potents cell.

Eosinophils↗
PubMed1990

Albumin, bradykinins, and eosinophil cationic protein on the nasal mucosal surface in patients with hay fever during natural allergen exposure.

This study examined plasma- and eosinophil-derived products in nasal lavage fluids obtained from patients with hay fever during natural allergen exposure. Nine patients with strictly seasonal allergic rhinitis and five normal, nonallergic subjects (control group) were studied. Nasal lavages were performed twice weekly, starting 1 week before the expected birch-pollen season and continuing for 6 weeks, thereby covering the entire birch-pollen season. Nasal symptoms and pollen counts were recorded daily. The lavage fluid was analyzed for it content of albumin, bradykinins, and eosinophil cationic protein (ECP). During the pollen season, each of these solutes was significantly increased in the nasal lavage fluid from the allergic patients (p less than 0.05) but not from the control subjects. Albumin, bradykinins, and ECP generally correlated better between themselves than with symptoms and pollen counts. We conclude that natural exposure to allergens induces plasma exudation and increased levels of ECP on the human nasal mucosa.

Adolescent↗
PubMed1990

Allergen-induced increase of eosinophil cationic protein in nasal lavage fluid: effect of the glucocorticoid budesonide.

It was our aim to study the effect of nasal allergen provocation on the concentration of eosinophil cationic protein (ECP) in nasal lavage fluid, with and without glucocorticoid pretreatment. Twenty grass-pollen sensitive volunteers were provoked outside the pollen season on 2 consecutive days after pretreatment for 2 weeks with the glucocorticoid, budesonide, as a nasal spray (400 micrograms/day) and with placebo with a double-blind, crossover design. Nasal lavage fluid was repeatedly collected during a 10-hour period to study both early and late-phase responses. 99mTechnetium-albumin was added to the lavage fluid, making it possible to calculate the amount of secretion and the degree of dilution. The results were as follows: (1) There was no correlation between ECP concentration and dilution factor in the individual samples. (2) The mean concentration of ECP in lavage fluid from untreated, prechallenge noses was 400 micrograms/L. (3) The ECP level did not increase during the early phase response. (4) There was a late occurring increase in the ECP concentration (6 to 24 hours). (5) This increase was completely inhibited by budesonide pretreatment. (6) The glucocorticoid therapy also reduced the prechallenge ECP concentration. In conclusion, allergen provocation in the nose results in a late occurring increase of ECP in nasal lavage fluid, and one of the therapeutic effects of topical glucocorticoid therapy may be an inhibition of the allergen-induced increase of this cytotoxic molecule.

Adult↗
PubMed1990

Exercise-induced asthma and the generation of neutrophil chemotactic activity.

Heat-stable neutrophil chemotactic activity (HS NCA) has been demonstrated in serum of subjects with asthma after exercise and after allergen inhalation challenge. Heat-labile neutrophil chemotactic activity (HL NCA) has been investigated only after allergen inhalation challenge. In this study, we have measured HS NCA and HL NCA after exercise of 22 adult patients with asthma, 13 of whom had exercise-induced asthma (EIA). In the 13 patients, the effect of pharmacologic pretreatment on the generation of HS NCA and EIA was evaluated in a double-blind study with inhalation of either disodium cromoglycate, terbutaline, or budesonide 15 minutes before exercise. Additionally, the effect of 4 weeks of treatment with budesonide aerosol was evaluated in an open study. A significant increase (p less than 0.01) in HS NCA was found in the patients with EIA with peak activities 15 minutes after exercise. In patients without EIA, the activity of HS NCA was variable. No HL NCA was detectable after exercise. EIA was inhibited by disodium chromoglycate, terbutaline, and 4 weeks of treatment with budesonide. The generation of HS NCA was more or less inhibited by all three drugs with 4 weeks of treatment with budesonide as the most potent regimen. No late-phase asthmatic reactions to exercise were found. It is concluded that only HS NCA is generated after exercise of subjects with asthma and that this production is controlled by antiasthmatic drugs. However, the generation of HS NCA occurs irrespective of EIA.

Adult↗
PubMed1990

Migratory responses of eosinophil and neutrophil granulocytes from patients with asthma.

In the present study the migratory function of eosinophil and neutrophil granulocytes from patients with asthma were investigated. Fifty-seven patients with asthmatic disease of varying severity were included. Eosinophil and neutrophil chemotactic responses to 5% pooled normal human serum (NHS), 5% allergen-challenge serum, 2.5% zymosan-activated serum, N-formyl-methionyl-leucyl-phenylalanine (10 nmol/L), chemokinetic responses to albumin (2 gm/L) and 5% NHS, and the eosinophil and neutrophil chemotactic and chemokinetic activities of serum were investigated. Eosinophils from patients with asthma demonstrated significantly (p less than 0.02) increased chemotactic responses to allergen-challenge serum, zymosan-activated serum, and N-formyl-methionyl-leucyl-phenylalanine, compared with eosinophils from references. The chemokinetic responses to albumin and NHS were increased (p less than 0.01) by eosinophils from the patients who had blood eosinophilia (greater than 400 X 10(6)/L). Sera from the patients with asthma demonstrated raised eosinophil chemotactic activity (p less than 0.001) and raised eosinophil and neutrophil chemokinetic activity (p less than 0.001). The eosinophil chemokinetic activity of serum was correlated to the relative peak expiratory flow rate of the patients (r = -0.43; p less than 0.02). The increased migratory responses were specific for the eosinophils, since the migratory responses of their neutrophils were not altered compared with that of the references. These results suggest that the eosinophils from the patients with asthma had been exposed to a priming mechanism in vivo.

Adolescent↗
PubMed1990

Immunotherapy abrogates the generation of eosinophil and neutrophil chemotactic activity during pollen season.

In a group of 40 birch pollen-allergic patients with a history of rhinoconjunctivitis and wheezing during the pollen season, 20 were immunotherapy (IT) treated preseasonally with birch-pollen extract (Pharmacia, Uppsala, Sweden). Blood samples for determination of the levels of heat-labile eosinophil chemotactic activity (HL-ECA), heat-labile neutrophil chemotactic activity (HL-NCA), and heat-stable neutrophil chemotactic activity were collected before the season, at the beginning of the study, at the start of the season, at the peak, at the end, and after the birch-pollen season. The symptoms from rhinoconjunctivitis and airways, peak expiratory flow, and use of medication were recorded throughout the season. Significant increases of HL-ECA and HL-NCA were observed in untreated compared with IT-treated patients at the start of the season (p less than 0.0001 for both activities) and at the peak of the birch-pollen season (p less than 0.0005 and p less than 0.01, respectively). At the end of the season, HL-ECA levels were not significantly different between the patient groups, whereas HL-NCA levels were still higher in untreated patients (p less than 0.005). We conclude that IT completely abrogates the generation of HL-ECA and HL-NCA during a pollen season.

Adolescent↗
PubMed1990

The eosinophil granulocyte in psoriasis.

The presence of eosinophils and eosinophil cationic protein (ECP) in the involved and non-involved skin in patients with psoriasis was studied using a polyclonal antibody specific for ECP and a monoclonal antibody (EG2) specific for activated eosinophils and secreted ECP. ECP immunoreactive eosinophils were found in all the specimens from involved psoriatic skin. In new lesions in patients with rapidly progressive disease, intense ECP immunoreactivity was detected both intra- and extracellularly, particularly in the upper third of the epidermis and usually in association with granulocytes. In stable or slowly progressive lesions, less ECP was observed. The EG2-immunoreactivity was positive in the same areas. ECP was also determined in suction-blister fluid from lesional and non-involved skin in psoriasis patients and in healthy subjects. The ECP concentration was greatly elevated in the fluid from lesions in patients with more acute and progressive disease.

Adolescent↗
PubMed1990

Changes in non-specific nasal reactivity and eosinophil influx and activation after allergen challenge.

It has been suggested that the eosinophilic granulocyte plays a crucial role in the genesis of increased reactivity of the airways. In order to characterize changes in non-specific reactivity in the upper airways following a nasal allergen challenge further 16 subjects with strictly seasonal allergic rhinitis were studied. They were challenged with allergen outside the relevant pollen season and monitored at intervals for a period of 24 hr for nasal symptoms, changes in nasal reactivity, eosinophil influx and activation, and markers of inflammation. The same challenge sequence without an initial allergen challenge was used as a control. A symptom score technique was used to record nasal symptoms and methacholine challenges were used to monitor changes in non-specific reactivity. A nasal lavage was made prior to each methacholine challenge to monitor the influx of cells, specifically eosinophils, and to determine changes in the levels of eosinophil cationic protein (ECP) and TAME-esterase activity. Cells from the mucosal surface were also collected with a Rhinobrush prior to the allergen challenge as well as at the 24-hr follow up. The allergen challenge induced a five-fold increase in non-specific nasal reactivity, as measured by the methacholine challenges, at the 2-hr follow up from 0.051 ml +/- 0.012 (mean +/- s.e.m.) to 0.255 +/- 0.062 (P less than 0.01) and a significant increase was also noted at all observation points, whereas no increases could be observed in the control setting.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Periodontitis in the primary dentition associated with Actinobacillus actinomycetemcomitans infection and leukocyte dysfunction. A 3 1/2 year follow-up.

2 siblings, aged 5 years (girl) and 7 years (boy), with periodontitis in the primary dentition were studied. Actinobacillus actinomycetemcomitans was isolated from the gingival pockets of both children. The titers of IgG antibodies against A. actinomycetemcomitans were elevated, and the polymorphonuclear leukocytes had a decreased capacity to ingest IgG-coated latex particles. Other functions of the polymorphonuclear leukocytes were normal. After antibiotic therapy and for the 7-year-old boy, debridement of the gingival pockets A. actinomycetemcomitans was no longer detectable in the gingival pockets, and the phagocytic capacity of the polymorphonuclear leukocytes was normalized. After 2 1/2 years, A. actinomycetemcomitans was found again in the gingival pockets of the boy, and once more his polymorphonuclear leukocytes had a decreased capacity to ingest IgG-coated latex particles. The antibiotic therapy was repeated and 6 months later, the number of A. actinomycetemcomitans was very low and the phagocytic capacity of the polymorphonuclear leukocytes was back to normal. This case report suggests that A. actinomycetemcomitans may be involved in the etiology of periodontitis in the primary dentition, possibly by triggering a phagocytic dysfunction of polymorphonuclear leukocytes.

Actinobacillus Infections↗