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Biomedical subjects

P Venge

Publications and source records attributed to P Venge.

At least 253 records · Page 14Linked to original sources
PubMed1989

The eosinophil component of the alveolitis in idiopathic pulmonary fibrosis. Signs of eosinophil activation in the lung are related to impaired lung function.

The number of eosinophils and the concentrations of eosinophil cationic protein (ECP), a specific granule constituent of eosinophil granulocytes, were measured in bronchoalveolar lavage (BAL) fluid from patients (n = 22) with idiopathic pulmonary fibrosis (IPF). The median recovery of eosinophils during lavage performance was 4% (range, zero to 49) of the nonepithelial cells and significantly increased compared with the recovery in healthy control subjects (less than 1%) and in control patients with sarcoidosis (1%; range, zero to 7). The median BAL fluid concentration of ECP was in IPF 13.3 micrograms/L (range, 2 to 118) and significantly increased compared with the concentrations in healthy control subjects (2.7 micrograms/L; range, less than 2 to 8) and in control patients (6.6 micrograms/L; range, less than 2 to 64). The BAL fluid concentrations of myeloperoxidase (MPO) were also significantly increased in IPF, indicating a local neutrophil activation. A significant correlation was found between BAL fluid ECP and MPO, suggesting a common activator of eosinophils and neutrophils. BAL fluid eosinophils and ECP correlated with the reduced diffusion capacity of the lung but not with vital capacity or forced expiratory volume. It is concluded that eosinophil activation is part of the inflammatory process in IPF. ECP and other cytotoxic eosinophil products may play a pathophysiologic role for the lung damage in this disease.

Adult↗
PubMed1989

Chemiluminescence of polymorphonuclear leukocytes and whole blood during acute bacterial infection.

The purpose of this study was to follow the changes in oxidative metabolism of polymorphonuclear leukocytes (PMN) and whole blood, during and after an acute bacterial infection, in otherwise healthy individuals, with the hypothesis that the majority of the subnormal activities found at clinical investigation of PMN functions in this respect, as part of the investigation of individuals with increased susceptibility to bacterial infections, is explained by subclinical infections or consequences of recent infections. 10 patients were followed from the day of admission and up to 80 days after the acute illness. Luminol- but not lucigenin-enhanced chemiluminescence (CL) of PMN was increased during the febrile period and normalized in parallel with normalization in body temperature. Both luminol- and lucigenin-enhanced CL were enhanced in whole blood during the period of fever. Subnormal activities of luminol- or lucigenin-enhanced CL were only seen sporadically. We conclude that the oxidative metabolism of PMN, as measured by lucigenin-enhanced CL, is virtually unaffected cause of the increased luminol-enhanced CL during the acute illness is suggested to be due to the increase mobilization of myeloperoxidase.

Acridines↗
PubMed1989

Coagulation and fibrinolysis during the normal menstrual cycle.

Thirteen healthy women (age 24-44 yrs) were studied during their menstrual cycle. Samples were taken 2-3 times weekly for six consecutive weeks. Plasma concentrations of oestradiol and progesterone were determined in each blood sample and only women found to be ovulatory were included. From the hormone data the cycles were divided in five phases (early follicular phase, late follicular phase, early luteal phase, late luteal phase and menstrual period). The samples for the coagulation and fibrinolysis assays as well as the venous occlusion (20 min) tests were drawn or performed between 8-9 a m after fasting for 8 hrs. The fibrinogen F VIII:C and AT III were assayed and did not show any variations through the study period. Neither were any differences found in platelet counts, platelet mean volumes or platelet function measured as platelet adhesion and plasma beta-thromboglobulin. The fibrinolytic activity after venous occlusion decreased slightly during the late luteal phase (phase 4) as compared with the other phases. Large individual differences were, however, seen and no statistically significant differences between the five different phases were found. The plasminogen activator inhibitor (PAI-1) varied during the cycle but in most individuals within the normal range. In 7/13 women substantial fluctuations of the fibrinolytic activities during the cycle were seen. Four women had a significant fall of the fibrinolytic activity after venous occlusion during the late luteal phase (phase 4) and 3 others during the menstrual phase (phase 5). No co-variation between the fibrinolytic activities and PAI-1 was found. Multiple regression analysis showed a co-variation between fibrinolytic activities and progesterone.

Adult↗
PubMed1989

Are blood eosinophil number and activity important for the development of the late asthmatic reaction after allergen challenge?

A role for eosinophils in chronic asthma has recently gained substantial support. We hypothesized that in addition to eosinophil chemoattractants released in the lung, the availability of a sufficient number of blood eosinophils to be recruited and their increased activity are prerequisites for the development of asthma. To test this hypothesis the blood eosinophil number and serum levels of ECP (eosinophil cationic protein were measured before allergen challenge of 13 allergic asthmatics. Each individual was pretreated with either placebo or four inhalant anti-asthmatic drugs at random and blind in order to modulate the late asthmatic reaction (LAR). Irrespective of premedication the blood eosinophil number and serum-ECP levels were significantly higher before challenge when the challenge resulted in LAR. Only corticosteroids abrogated the development of LAR and also significantly reduced eosinophil activity as measured by serum-ECP. Thus the inherent activity of a sufficient number of eosinophils may be important determinants for the expression of allergic asthma.

Adult↗
PubMed1988

The effect of immunotherapy on bronchial hyperresponsiveness and eosinophil cationic protein in pollen-allergic patients.

The effect of immunotherapy (IT) on bronchial response to histamine and on eosinophil cationic protein (ECP) in 40 birch pollen-allergic patients with a history of rhinoconjunctivitis and wheezing during the birch season was examined. Twenty patients started IT with birch extract (Pharmacia, Uppsala, Sweden) before the season. The other 20 patients were not treated with IT. Histamine-challenge tests were performed before, at the start, at pollen peak, at the end, and after the birch-pollen season. Blood samples for determination of ECP were collected at the same time. Skin prick tests and nasal provocation tests were also performed before and after the season. A significant increase in bronchial hyperresponsiveness was noted in the group treated with IT and in the untreated group during the season. The increase was greatest in the untreated group with the maximal difference between the two groups at the end of the pollen season (p less than 0.07). IT treatment was followed by significantly less medication and higher peak expiratory flow values. The levels of ECP increased during the season in untreated patients (p less than 0.05) but not in patients treated with IT. The ECP levels of patients from both groups correlated significantly with histamine sensitivity (p less than 0.001).

Allergens↗
PubMed1988

Active participation of eosinophils in patch test reactions to inhalant allergens in patients with atopic dermatitis.

Intracutaneous testing and patch tests with house dust mite and grass pollen allergens were performed in patients with atopic dermatitis. Only patients with an immediate type skin reaction to house dust mite or grass pollen allergens showed a positive patch test reaction to these allergens 24-48 h after testing. Occasionally positive patch test reactions at 20 min, 2 h and 6 h were also observed. Patch test reactions were not found in normal controls or atopic patients without atopic dermatitis. Analysis of the cellular infiltrate demonstrated an influx of eosinophils into the dermis, starting from 2-6 h after patch testing. Immunostaining with antibodies against granular constituents of the eosinophils revealed that the infiltrating eosinophils were in an activated state and had lost part of their granular contents. At 24 h eosinophils also appeared in the epidermis. Electron microscopy showed that in the epidermis, some eosinophils were in close contact with Langerhans cells, suggesting a cell-cell interaction. Taken together, these results strongly suggest an active role for eosinophils in patch test reactions to inhalant allergens in atopic dermatitis patients.

Adolescent↗
PubMed1988

Lactoferrin, myeloperoxidase, lysozyme and eosinophil cationic protein in exudate in delayed type hypersensitivity.

A skin window technique was used to study the morphology of leucocytes in upper dermis and exudate during nickel challenge in patients with contact allergy to nickel. Contact allergic patients and healthy volunteers tested with a skin widow without addition of nickel to the chamber medium served as controls. The morphology of the leucocytes in dermis was studied in biopsies taken 8, 24, or 48 h after skin window application, and in a parallel test the morphology of the exudate was examined by sequential collection of the chamber medium during a 48 h period. The infiltrate in dermis of contact allergic patients with nickel challenge in the chamber medium showed a time-dependent increase of mononuclear cells, eosinophils and basophils and a concomitant decrease of polymorphonuclear granulocytes, characteristic of a combined specific and unspecific inflammation. The morphology of the exudate in contact allergic patients exposed to nickel showed a dominance of polymorphonuclear granulocytes throughout the study period, while mononuclear cells, eosinophils and basophils were detected at a much lower quantity and with a considerable delay. Further, we studied the kinetics of the leucocyte granule proteins: lactoferrin, myeloperoxidase, lysozyme and eosinophil cationic protein in exudate fluid in a parallel test. A significant higher flux was found for all during the second day of allergen exposure compared to contact allergic patients without allergen challenge as well as normal volunteers. The increased protein fluxes were not accompanied by an increased flux of polymorphonuclear granulocytes in the exudate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Total absence of eosinophils in a patient with chronic urticaria and vitiligo.

A 71-year-old woman with chronic urticaria and vitiligo is reported who lacked eosinophil and basophil leukocytes in her blood, bone-marrow and skin. No IgE was detectable in serum. She had a low level of serum eosinophil cationic protein (ECP) which could indicate that some eosinophils had been formed but rapidly destroyed. There was, however, no ECP release when the patient's serum was mixed with heterologous eosinophils. Staining for eosinophilic proteins in white blood cells by monoclonal antibodies revealed no storage or secreted forms of ECP. The source of ECP in our patient therefore remains unknown.

Aged↗
PubMed1988

Purification and characterization of eosinophil cationic protein from normal human eosinophils.

ECP (eosinophil cationic protein) was purified in high yield from the granules of human buffy coat eosinophils obtained from healthy individuals. The separation procedure included gel filtration on Sephadex G-75, ion-exchange chromatography on Bio Rex 70, and chelating chromatography on zinc-chelate Sepharose 6B. The normal ECP is a single-chain, highly cationic glycoprotein which separates on SDS-polyacrylamide gel electrophoresis into at least 3 molecular weight forms, with molecular weights of 18.5, 20 and 22 kDa. A heterogeneity in charge was also observed, with the 18.5 kDa form being the most cationic one. The various molecular species of ECP exhibited antigenic identity, identical amino acid compositions, and identical amino-terminal amino acid sequences. The molecular heterogeneity was shown to be caused by differences in glycosylation of the protein.

Amino Acid Sequence↗
PubMed1988

Neutrophil and eosinophil involvement of the small bowel affected by chronic alcoholism.

Excessive ethanol intake may affect the intestinal mucosa functionally and morphologically. The ethanol effect could partly be the result of inflammatory mechanisms, possibly reflected by an enhanced local granulocyte turnover. This study investigated habitual alcoholics by segmental perfusion of the jejunum and analysed the perfusion fluid content of granulocyte granule constituents. The mean jejunal secretion rate of myeloperoxidase (MPO), a neutrophil granule constituent, was 152 (26) (SE) ng/min/40 cm jejunal segment in the controls (n = 16). The MPO secretion rate in non-cirrhotic habitual alcoholics (n = 7) was on average 450 (103) ng/min and significantly increased compared with controls (p less than 0.001). In contrast alcoholics with cirrhosis (n = 6) had normal MPO secretion rate. The mean secretion rate of eosinophil cationic protein (ECP), an eosinophil granule constituent, was in the controls 77 (15) ng/min/40 cm jejunal segment. Corresponding values in non-cirrhotic and cirrhotic alcoholics were 141 (38) and 130 (93) ng/min, respectively (ns). The data suggest an enhanced neutrophil granulocyte turnover in the jejunum in alcoholics, possibly contributing to the ethanol induced affection of the small bowel. The lack of increased neutrophil activity in cirrhotic alcoholics may reflect a role of the liver for granulocyte activity.

Adult↗
PubMed1988

Eosinophil granule proteins in serum after allergen challenge of asthmatic patients and the effects of anti-asthmatic medication.

Thirteen allergic asthmatic patients were challenged six times each and serum levels of ECP (eosinophil cationic protein), EPX (eosinophil protein-x) and blood counts of eosinophil granulocytes were measured in blood obtained before and at regular intervals after challenge. Three challenges were performed in a blinded and randomized fashion and included a one-dose pretreatment with the inhalant anti-asthmatic drugs disodium cromoglycate, terbutaline and budesonide. One challenge was performed after 4 weeks' pretreatment with the inhalant budesonide and one was a histamine challenge. Pre-challenge levels of ECP were significantly reduced both after 4 weeks and after a one-dose treatment with budesonide whereas the EPX levels were reduced only after the former. Blood eosinophil counts were unaffected by the challenge whereas the ECP levels were significantly reduced after the placebo challenge and when premedicated with disodium cromoglycate and terbutaline. The EPX levels stayed unaltered at the placebo challenge but were significantly reduced when the patients were premedicated with terbutaline. ECP and EPX levels as well as blood eosinophil counts before challenge were significantly related to the development of the late asthmatic reaction. The results again focus on a relation between the eosinophil granulocyte and asthma and suggest that an increased activity of the blood eosinophil, as suggested by the raised serum levels of the granule proteins ECP and EPX, is one prerequisite for the development of chronic asthma.

Adult↗
PubMed1988

Epithelial injury by human eosinophils.

The human eosinophil is armed with a number of very potent cytotoxic granule proteins that upon extracellular release may produce considerable damage. The toxic effect of the proteins seems to be quite unselective, involving most mammalian and nonmammalian cells including the epithelial cells. The demonstration of a close relation between the deposition of eosinophil granule proteins and areas of epithelial cell destruction in a variety of diseases including asthma and the fact that cytotoxic concentrations of the proteins have been measured in the fluid phase suggest that the eosinophil participates actively in the pathogenesis of airway diseases. The protection towards the adverse actions of the eosinophil, particularly towards their proteins, therefore seems vital. The discovery of alpha-2-macroglobulin as a specific binder of eosinophil cationic protein may be relevant in this regard.

Asthma↗
PubMed1988

Activation of inflammatory systems during cardiopulmonary bypass.

"Whole body inflammation" induced by cardiopulmonary bypass may play a role in the pathogenesis of postoperative complications after open-heart surgery. The inflammatory response, in terms of complement activation and release of granular proteins from neutrophil granulocytes, was investigated in six patients undergoing aortocoronary bypass surgery. Complement activation was demonstrated as well as substantially increased plasma levels of lactoferrin and myeloperoxidase--two granulocyte factors. The activation of inflammatory systems probably takes place on the artificial surfaces of the extracorporeal device. The biocompatibility of these components therefore should be further studied.

Aged↗
PubMed1988

Oral N-acetylcysteine reduces selected humoral markers of inflammatory cell activity in BAL fluid from healthy smokers: correlation to effects on cellular variables.

Bronchoalveolar lavage (BAL) was performed on eleven healthy smokers before and after eight weeks of oral treatment with N-acetylcysteine (NAC) 200 mg t.i.d. The concentrations of selected eosinophil and neutrophil granule constituents and of selected proteases and protease inhibitors, albumin and endotoxin were determined in the recovered BAL fluid and in plasma or serum samples. In addition, in vitro chemotactic activities for neutrophils and eosinophils were assessed in the BAL fluid. Significant reductions in BAL fluid content of lactoferrin (LF), eosinophil cationic protein (ECP), antichymotrypsin (ACT) and chemotactic activity for neutrophils were recorded after NAC treatment. The levels of other examined markers tended to be reduced or were not affected. In serum/plasma, the concentrations of myeloperoxidase (MPO) and elastase were reduced after NAC treatment whereas concentrations of other constituents examined were unaltered. These data, together with previously reported findings, suggest that oral NAC may influence the activity of "inflammatory" cells in the bronchoalveolar space of smokers.

Acetylcysteine↗
PubMed1987

Interaction and complex-formation between the eosinophil cationic protein and alpha 2-macroglobulin.

The interaction between the highly basic and cytotoxic eosinophil cationic protein (ECP) and human plasma proteins is described. The major plasma protein responsible for complex-formation with ECP was shown to be the 'fast' form of alpha 2-macroglobulin (alpha 2M). Large amounts of complexes were observed in a serum obtained from a patient with hypereosinophilic syndrome. The amount of complexes that could be generated in vitro in normal fresh serum was rather low and was even less in fresh citrated plasma. Complex-formation between the non-proteolytic ECP and alpha 2M was augmented in the presence of methylamine. Binding of ECP to alpha 2M was also induced by the proteinases cathepsin G and thrombin, and the binding was competitive with cathepsin G. Methylamine and the proteinases seem to share a common mechanism in inducing binding of ECP. The nature of the ECP-alpha 2M interaction is non-covalent, but withstands high salt concentrations. The interaction with alpha 2M may reflect a mechanism by which the organism protects itself against the deleterious effects of the highly cytotoxic protein ECP.

Blood Proteins↗
PubMed1987

The molecular basis of the hyaluronic acid-mediated stimulation of granulocyte function.

Previous investigations have demonstrated that the function of polymorphonuclear leukocytes (PMN) is stimulated by hyaluronic acid (HA). The aim of the present investigation was to study the molecular basis for the effect of HA. HA fragments of m.w. in the range from 792 (tetrasaccharide) to 3,000,000 all stimulated the chemotactic and phagocytic function of PMN. The active concentration ranged from 4 to 64 pmol/liter, irrespective of the molecular size. Further investigations demonstrated that N-acetyl-D-glucosamine (NAGA) was the smallest active fragment of HA. NAGA is one of the components from which HA is built up; the other component glucuronic acid was without effect, and so were the other glycosaminoglycans, N-acetyl-D-mannosamine, N-acetyl-D-galactosamine, and D-glucosamine. Finally, Con A, the glucopyranosyl and glucomannosyl binding lectin, inhibited the stimulatory effect of NAGA. As is the case with HA, fibronectin also acts as a necessary cofactor to NAGA when incubations are made in the absence of whole blood or serum. The present results strongly indicated that the combined action of NAGA and fibronectin worked directly on the PMN by an interaction at the cellular membrane level. We conclude that the stimulatory action of HA on granulocyte functions is mediated through one of its two structural components, i.e., NAGA.

Acetylglucosamine↗
PubMed1987

New method for the measurement of eosinophil migration.

A new application of the Boyden chamber method for the measurement of eosinophil migration, without the need of eosinophil isolation, has been developed. A cell suspension containing a mixture of granulocytes, neutrophils to the greater part, was used. The eosinophils were identified by staining their granules with Chromotrope 2R. The method made it possible to study the migration of eosinophils from normal individuals without eosinophilia. Control experiments demonstrated that the chemotactic and chemokinetic response of eosinophils in the granulocyte mixture was in accordance with the response of isolated eosinophils from the same donor. Normal eosinophils demonstrated a significant chemotactic response to C5f, platelet-activating factor (PAF), leukotriene B4 (LTB4), and f-meth-leu-phe (f-MLP). Furthermore, PAF was demonstrated to be significantly more eosinophil chemotactic than neutrophil chemotactic.

Caseins↗