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Biomedical subjects

P Venge

Publications and source records attributed to P Venge.

At least 271 records · Page 15Linked to original sources

Neutrophil locomotion and serum chemotactic and chemokinetic activities in pustulosis palmoplantaris compared with psoriasis.

Twenty patients with palmoplantar pustulosis (PPP) and 21 patients with psoriasis were compared with respect to the chemotactic response and random migration of their neutrophils (PMNs) and to the chemotactic and chemokinetic activities of their serum. The Boyden chamber technique was used. Compared with the reference group, the PPP neutrophils showed a significant decrease in random migration (p = 0.036) and chemotactic response to casein (p = 0.031), but not to zymosan-activated serum. The psoriasis PMNs had normal chemotactic response, but decreased random migration (p = 0.001). The chemokinetic effects of serum from PPP and psoriatic patients on normal neutrophils were increased (for PPP, p = 0.019 and for psoriasis p = 0.024). The chemokinetic activity of the heated sera was decreased and inversely correlated to the serum level of IgA in both disorders (PPP, p = 0.021; psoriasis, p = 0.013). The chemotactic activity of serum on normal PMNs was decreased in both conditions (PPP, p = 0.001; psoriasis, p = 0.047); this was due to the presence of chemotactic factor inhibitors in 34% of the sera. It seems likely that the high chemokinetic effect of serum both from the PPP and from the psoriasis patients compensates for the slightly low or normal migratory activity of neutrophils from these patients.

Adolescent↗

Heat-labile neutrophil chemotactic activity in subjects with asthma after allergen inhalation: relation to the late asthmatic reaction and effects of asthma medication.

Neutrophil chemotactic activity (NCA) in serum is raised in subjects with asthma after inhalation of an allergen. Two kinds of NCA have been demonstrated, heat-stable and heat-labile. In addition, inhibitory activity is generated after inhalation challenge. In the present study we have investigated the relationship of heat-labile NCA to the development of the late asthmatic reaction (LAR) in 13 subjects with asthma after allergen challenge and the effects of asthma medication on the formation of this activity. Heat-labile NCA peaked 120 to 240 minutes after challenge and demonstrated at this time significant (p less than 0.001) quantitative relationships to the ensuing LAR. The inhalant corticosteroid, budesonide, significantly inhibited (p less than 0.001) the generation of heat-labile NCA and the development of LAR both after a single dose and after 4 weeks of pretreatment. Single-dose disodium cromoglycate pretreatment, initially, slightly enhanced (p less than 0.05) heat-labile NCA but, after 120 minutes, slightly inhibited (p less than 0.05) the activity. Disodium cromoglycate also slightly abrogated the development of LAR. Single-dose pretreatment with the beta 2-agonist, terbutaline, inhibited generation of heat-labile NCA (p less than 0.001) but was without effect on LAR. It is concluded that the generation of heat-labile NCA is related to the development of the LAR and may be of importance for the attraction of inflammatory cells to the lung in the development of the inflammatory reaction probably responsible for LAR. However, the pharmacologic control of heat-labile NCA indicates that the process is multifactorial and not solely dependent on the generation of NCAs detected in serum.

Adult↗

Beta 2-microglobulin, lysozyme and lactoferrin in cerebrospinal fluid in patients with lymphoma or leukaemia: relationship to CNS involvement and the effect of prophylactic intrathecal treatment with methotrexate.

Central nervous system (CNS) involvement in patients with leukaemia or lymphoma presents a diagnostic problem. This study was conducted to test whether combined measurements of various cellular markers such as beta 2-microglobulin (beta 2m), lactoferrin (LF) and lysozyme (LYS) in the cerebrospinal fluid (CSF) might aid in the diagnosis of CNS involvement in such patients. Forty-two patients were studied. Sixteen were considered to have CNS involvement and 26 showed no signs of such involvement. In the group with symptoms or signs of CNS involvement, nine patients out of 12 had increased total protein in CSF, 14 of 14 increased beta 2m, 14 of 16 increased LYS and five of 15 increased LF. In patients without CNS involvement total protein was increased in four of 25, beta 2m in three of 21, LYS in four of 28 and LF in one of 28 patients. The differences were statistically significant (P less than 0.01, P less than 0.001, P less than 0.001 and P less than 0.05, respectively). Prophylactic intrathecal methotrexate treatment in patients with acute lymphoblastic leukaemia caused an increase in the CSF of beta 2m, LYS and LF but not of total protein, which may reflect a drug-induced inflammatory reaction in the CNS. We conclude that combined measurements of the three cell markers add to our understanding of the cellular reaction to malignant cells in the CNS in leukaemia and lymphoma and may be valuable supplements in the diagnosis of this CNS involvement.

Adolescent↗

Eosinophil cationic protein and myeloperoxidase in nasal secretion as markers of inflammation in allergic rhinitis.

The inflammatory component of allergic rhinitis was studied by measuring the concentration and content of eosinophil cationic protein (ECP, specific for eosinophils) and myeloperoxidase (MPO, specific for neutrophils) in samples of nasal secretion from 20 pollen-allergic subjects. All secretion samples contained measurable concentrations of both proteins. The mean ECP concentrations on two occasions without pollen exposure were 950 and 1170 micrograms/l. The ECP concentration during the pollen season without any therapy (mean 1160 micrograms/l) did not differ significantly from the baseline values, but intranasal corticosteroid therapy resulted in a significant decrease (mean 530 micrograms/l). The concentration of MPO was about 10 times higher than that of ECP, but the changes in MPO were nonsignificant throughout the observation period. An inverse correlation was found between the threshold dose in histamine challenges and the ECP level expressed either as concentration or as content. Furthermore, the ECP concentration and content 1 day after a positive allergen challenge were both significantly correlated with the strength of the challenge reaction. Measurements of ECP in nasal secretions are useful for studying the presence and activity of eosinophils in the nasal mucosa, and may prove of value in clinical investigations on patients with allergic rhinitis.

Adolescent↗

Myeloid regeneration after bone-marrow transplantation monitored by serum measurements of myeloperoxidase, lysozyme and lactoferrin.

Bone-marrow regeneration after chemo- and radiotherapy-induced aplasia can be monitored by serum levels of myeloperoxidase (MPO), lysozyme (LYS) and lactoferrin (LF). In 10 patients with leukemia, serum measurements were performed before and after bone-marrow transplantation. Bone-marrow regeneration was suggested by increments in serum MPO and LYS 5 and 4 days prior to the increase in mononuclear cells (Mono) and 10 and 9 d before the increase in polymorphonuclear leukocytes (PMN) in the peripheral blood. LF started to rise 4.5 d before detectable circulating PMNs. 2 patients with early relapses of leukemia post transplantation are shown to display atypical patterns of serum MPO and LYS. We conclude that serum measurements of MPO, LYS and LF may be used as early and sensitive means to monitor bone-marrow activity during hematological regeneration. However, the findings also strongly support the earlier proposal that MPO alone may be used to reflect myeloid activity in the bone-marrow in general.

Adolescent↗

Specific binding of B-CLL cell-derived chemokinetic inhibitory factor (CIF) to human polymorphonuclear leukocytes.

The chemokinetic inhibitory factor (CIF) is a recently described B-cell derived lymphokine that mediates a chemokinetic inhibitory effect on human polymorphonuclear leukocyte (PMN) migration. In the present report the interaction of CIF with the neutrophil plasma membrane was studied. Normal human peripheral blood neutrophils and purified neutrophil plasma membranes selectively removed biologic activity from CIF-containing concentrates obtained during the purification procedure from conditioned medium. Removal was obtained at both 4 degrees C and 37 degrees C. Furthermore, HL-60 cells treated with dimethyl sulfoxide removed CIF activity (granulocyte-like cells) but HL-60 cells treated with 12-O-tetradecanoylphorbol-13-acetate (macrophage-like cells) did not. Purified human blood monocytes, cells from the macrophage-like U-937 cell line and cells from the basophilic leukemia cell line KU-812 did not remove CIF. These studies suggest that neutrophils express specific binding sites for CIF-activity.

Binding Sites↗

Serum and plasma measurements of neutrophil granule proteins during cardiopulmonary bypass: a model to estimate human turnover of lactoferrin and myeloperoxidase.

During extracorporeal circulation (ECC), granule proteins such as lactoferrin and myeloperoxidase escape to the plasma in large amounts. ECC was used to study the turnover of these proteins and compare their variations in plasma and serum. During ECC both proteins rose to very high levels and the variations were similar in both serum and plasma (r = 0.93 for lactoferrin and 0.80 for myeloperoxidase). The initial elimination after termination of operation (t 1/2) was, for lactoferrin 0.75 and for myeloperoxidase 0.5 h. Both proteins followed a second order kinetics of elimination with a t 1/2 for lactoferrin of about 9 and for myeloperoxidase of about 25 h. 48 and 72 h postoperatively serum levels, but not plasma levels, of myeloperoxidase rose again 10-fold. We conclude that serum and plasma measurements of neutrophil granule proteins are complementary. The period after disconnection of the patient from the extracorporeal device may be used to estimate the turnover kinetics of neutrophil granule proteins.

Aged↗

Diagnostic and prognostic significance of serum measurements of lactoferrin, lysozyme and myeloperoxidase in acute myeloid leukemia (AML): recognition of a new variant, high-lactoferrin AML.

92 patients with acute myeloid leukemia were classified according to the FAB classification (M1 n = 20, M2 n = 43, M3 n = 1, M4 n = 19, M5a n = 2, M5b n = 2, and M6 n = 5 patients). Serum measurements of lactoferrin (LF), myeloperoxidase (MPO) and lysozyme (LYS) were performed before the start of treatment. LF was significantly lower in M1 when compared with M2 but not as compared to M4, MPO was significantly higher in M2 and M4 than in M1, but comparable MPO levels were found in M2 and M4. LYS was significantly elevated in M2 in comparison with M1, and in M4 when compared to both M1 and M2. Polymorphonuclear granulocytes (PMNs) in M1 were significantly reduced when compared with M2 and M4, whereas mononuclear cells were significantly increased in M4 in comparison with both M1 and M2. FAB classification did not generate any prognostic information. When the patients were, instead, subdivided according to LF levels were found prognostically significant differences. Of patients below 100 micrograms/l, 44% went into remission as compared to 77% with LF from 101 to 400 micrograms/l. In patients with LF levels above 400 micrograms/l the remission frequency was only 14%. Multivariate statistical analysis on the data further suggested that lactoferrin may be used as an independent prognostic indicator. We conclude that although determination of the serum-levels of lactoferrin, lysozyme and myeloperoxidase in certain cases may be valuable as a supplement to the morphological examination of acute myeloid leukemia, it is evident that none of the three determinations can be used alone to distinguish between the FAB groups.

Adult↗

Raised circulating levels of the eosinophil cationic protein in ankylosing spondylitis: relation with the inflammatory activity and the influence of sulphasalazine treatment.

The possibility of eosinophil involvement in ankylosing spondylitis (AS) was investigated by measuring serum levels of eosinophil cationic protein (ECP), a specific granule constituent of eosinophils. In a group of 48 patients with AS we found a threefold increase of the mean serum levels of ECP compared with a reference group (p less than 0.001). The blood eosinophil counts were similar in patients and controls. A correlation was found between ECP and inflammatory activity defined by erythrocyte sedimentation rate (ESR) and serum haptoglobin. Fifteen patients were studied before and after three months' treatment with sulphasalazine (2-3 g/day). The ECP levels decreased in 13/15 and this paralleled reduction of the acute phase reaction and improvement of clinical parameters. The results point to eosinophil activation as part of the inflammatory process in AS. The signs of reduced eosinophil activation during sulphasalazine treatment suggest either a drug mediated, direct effect on eosinophils or an effect on the inflammatory mechanism stimulating eosinophils.

Adult↗

Eosinophil activation in allergic disease.

The eosinophil granulocyte is a pro-inflammatory cell which in its granules contains an abundance of highly cytotoxic proteins such as eosinophil cationic protein, eosinophil-derived neurotoxin, eosinophil peroxidase, eosinophil protein X and major basic protein. Upon stimulation of the cell, these proteins as well as a number of lipid mediators such as leukotriene C4, prostaglandin and platelet-activating factor are released to the exterior. The molecules which are produced during inflammatory reactions of the allergic type attract eosinophils to the target organ and stimulate them to liberate their products. The physiological meaning of this reaction is probably to combat invading parasites; however, in their absence accumulation and activation of eosinophils may cause disease, and one such disease may be chronic asthma.

Asthma↗

Eosinophil chemotactic activity in allergic patients during the birch pollen season: the effect of immunotherapy.

Recently, heat-labile eosinophil chemotactic activity (ECA) has been found in serum after challenge of allergic asthmatic patients. In this study, we investigated changes in ECA in 40 birch-allergic patients during the birch pollen season; 20 of them had been treated with immunotherapy of birch pollen extract before the season. ECA raised significantly (p less than 0.001) in the untreated birch pollen-allergic patients during the season. Immunotherapy completely abolished this activity.

Adolescent↗

Eosinophil activation in the lung is related to lung damage in adult respiratory distress syndrome.

The concentrations of eosinophil cationic protein (ECP), a specific granule constituent of eosinophil granulocytes, were measured in bronchoalveolar lavage (BAL) fluid from patients with adult respiratory distress syndrome (ARDS). The mean level was 163 +/- 85 (SD) micrograms/L and significantly increased (p less than 0.001) compared with the levels in control subjects (19 +/- 18 micrograms/L). The BAL fluid concentrations of myeloperoxidase (MPO) were also significantly increased in ARDS, indicating a local neutrophil activation. A significant correlation was found between BAL fluid ECP and MPO, suggesting a common activator of eosinophils and neutrophils. No relation was seen between BAL fluid ECP or MPO and degree of complement consumption, suggesting that other mechanisms besides complement activation may underlie granulocyte activation in ARDS. Lavage ECP levels correlated strongly with the severity of lung damage defined by pulmonary oxygenation index (PaO2/inspired fraction of O2). Activation of eosinophils, neutrophils, and the complement system is not specific for ARDS but was also observed in patients after major surgery, but at a significantly lower level (p less than 0.001). It is concluded that eosinophil activation is part of the inflammatory process in the lung in ARDS. The association observed between elevated lavage fluid levels of ECP and reduced pulmonary function in ARDS might reflect a pathophysiologic role for ECP and other cytotoxic eosinophil products in this syndrome and should be evaluated.

Adult↗

Defective C3b receptor-mediated phagocytosis of neutrophils in patients with primary biliary cirrhosis.

Neutrophil function in patients with primary biliary cirrhosis (PBC) was studied by means of a kinetic particle uptake assay using IgG-coated and IgG + C3b-coated latex particles, enabling a differentiation between Fc and C3b receptor-mediated phagocytosis. C3b receptor-dependent phagocytic rate (delta C3b) in PBC was significantly decreased (PBC = 0.20, 0.08-0.51 min-1; reference = 0.37, 0.23-0.60 min-1; p less than 0.0005 (-x; +/- SD logarithmically transformed], whereas the Fc receptor-dependent phagocytic rate was normal. delta C3b was inversely correlated with complement factor C3 levels (r = -0.77, p less than 0.02) and C3b receptor-binding activity (r = 0.47, p less than 0.04) in PBC sera, indicating a possible relationship between serum components and neutrophil C3b receptor dysfunction. These observations are in accordance with previously reported defects of C3b receptor function in monocytes and lymphocytes, suggesting a generalized disturbance of C3b receptor-bearing cells in PBC. Furthermore, the effect of PBC sera on migratory function of normal neutrophils was investigated. PBC sera contained heat-labile, chemokinetic stimulating activity. The mean chemotactic activity of PBC sera did not differ from that of reference sera.

Adult↗

Human alveolar macrophages from smokers have an impaired capacity to secrete LTB4 but not other chemotactic factors.

The function of alveolar macrophages (AM phi s) was studied in terms of the secretion of various chemotactic factors. Human AM phi s were obtained by BAL from healthy non-smokers and smokers. One of the chemotactic factors was LTB4, an arachidonic acid metabolite of the lipoxygenase pathway. The amount of LTB4 was determined in culture medium, in cell homogenate and in BAL-fluid. The total chemotactic activity for neutrophils was measured in culture medium and in BAL-fluid. AM phi s from smokers showed an impaired secretion of LTB4. The spontaneous secretion in vitro was inhibited by 90% (p less than 0.05) and the stimulated one was blocked by 84% (p less than 0.05). This impairment was not followed by a decrease in total chemotactic activity, indicating the existence of other chemotactic factors than LTB4. Preliminary characterization of the chemotactic activity by gel filtration demonstrated at least four different chemotactic factors. Budesonide inhibited both the release of LTB4 and the total chemotactic activity in medium from stimulated AM phi s.

Bronchoalveolar Lavage Fluid↗

Myocardial and skeletal muscle function in habitual alcoholics and its relation to serum myoglobin.

Lower-than-normal serum myoglobin levels are regularly found in habitual alcoholics without recent alcohol intake and were also confirmed in this study. It was hypothesized that these low levels reflect reduction in myocardial and skeletal muscle function. To study this hypothesis, heart and skeletal muscle function was evaluated and related to serum myoglobin levels. Myocardial function evaluated by noninvasive techniques was significantly decreased and heart muscle mass increased (p less than 0.001) in circulatory asymptomatic alcoholics compared with age- and weight-matched healthy male control subjects. The working capacity of the alcoholics was lower than expected during dynamic exercise testing (p less than 0.001), and maximal muscle power was reduced during isokinetic muscle testing (p less than 0.05). Myoglobin levels were correlated to the degree of myocardial diastolic dysfunction (p less than 0.01) but not to working capacity during dynamic or isokinetic exercise testing. The observation that myocardial affection was related to low serum myoglobin suggests that the mechanisms behind reduced myoglobin release are linked to the chronic muscle affection in alcoholics.

Adult↗

An immunofluorescent method for a specific demonstration of granulocytes and some of their proteins (ECP and CCP).

Using p-benzoquinone as a fixative the non-specific fluorescence of granulocytes and especially the eosinophils is removed for both FITC and TRITC. In this way we have been able to detect the eosinophil cationic protein (ECP) and the chymotrypsin-like cationic protein (CCP) in human lung tissue and by double immunofluorescent labelling shown that these two proteins very likely are related to eosinophils respectively the neutrophils.

Adult↗

Bactericidal proteins and neutral proteases in diabetes neutrophils.

Reduced bacterial killing by polymorphonuclear leucocytes has been reported in patients with diabetes mellitus. Whether this is due to reduced content of bactericidal granular proteins has not been determined. We therefore immunochemically measured the content of myeloperoxidase, lactoferrin, lysozyme, cathepsin G and elastase in polymorphonuclear leucocytes from 50 insulin-treated diabetic patients. The peroxidase activity was also measured. Normal contents of myeloperoxidase and lactoferrin as well as normal peroxidase activity were found. The average contents of cathepsin G, elastase and lysozyme were 2.5, 3.2 and 2.6 micrograms/10(6) polymorphonuclear leucocytes, respectively, and thus 14, 45 and 18% higher than the contents of normal polymorphonuclear leucocytes. The results indicate that reduced intracellular killing of bacteria demonstrated in previous studies in diabetic patients does not appear to be related to a reduction in the content of bactericidal proteins.

Age Factors↗

Production of chemokinetic inhibitory factor (CIF) by normal blood and spleen B lymphocytes.

We have recently reported the partial purification and characterization of of a new lymphokine, the heat-labile chemokinetic inhibitory factor (CIF) which inhibits neutrophil movement. We have also shown that this lymphokine is produced and secreted by cultured B-chronic lymphocytic leukaemia (CLL) cells in vitro. The present study shows that highly purified resting normal B lymphocytes from blood and spleen have the capacity to produce CIF spontaneously. After activation with anti-IgM or EBV-infection the lymphocytes produced a number of other factors, heat-stable chemokinetic inhibitory factors and heat-labile chemokinetic enhancing factors. Supernatants from a collection of human B-cell lines representing different stages of B-cell differentiation were also investigated. None of these cell lines produced CIF. The present results show that the production of CIF is not restricted to the malignant B-CLL cell but is also produced by a subset of normal blood and spleen B cells.

B-Lymphocytes↗