Search PubMed⌕ Search

Biomedical subjects

P Venge

Publications and source records attributed to P Venge.

At least 325 records · Page 18Linked to original sources

Beta-thromboglobulin in inflammatory synovial fluid.

Activated platelets release substances which potentially can contribute to joint lesions in inflammatory arthritides. To elucidate a possible participation of platelets in inflammatory joint reactions, the concentrations of the platelet protein beta-thromboglobulin (beta-TG) were measured in 90 inflammatory synovial fluids. Seven percent of the patients with rheumatoid arthritis and none of the patients with other inflammatory joint diseases (e.g., Reiter's disease, reactive or crystal arthritides) had beta-TG concentrations in synovial fluid exceeding the upper normal range of plasma beta-TG. The absent or very modest signs of local platelet activation were contrasted by the pronounced neutrophilic and monocytic activation, as assessed by the measurements of some granule proteins: lactoferrin, myeloperoxidase, lysozyme, and ferritin. No correlation was found between these inflammatory cell markers and beta-TG. A positive correlation (p less than 0.001) was noted between beta-TG and beta 2-microglobulin, which appeared in particularly high amounts in rheumatoid arthritis. This correlation may reflect a disturbed permeability of synovial membrane for LMW proteins or a related activation of platelets and lymphocytes. The present results do not give any evidence of platelet activation playing a major role in proliferative or destructive processes in arthritis.

Adolescent↗

Eosinophil cationic protein (ECP) in the cerebrospinal fluid.

ECP (eosinophil cationic protein) has been measured by means of a specific radioimmunoassay in the cerebrospinal fluid (CSF) from 210 individuals with various diseases affecting the central nervous system. In the same specimens lactoferrin and albumin were measured as well, as indicators of neutrophil-involved inflammation and damage to the blood-brain barrier. From a patient reference group (n = 39) the upper "normal" limit for ECP was estimated to 1.7 microgram/l. In patients with acute cerebrovascular disease (n = 108) ECP levels were elevated in 38% of the cases which was a significantly (P less than 0.001) greater proportion than seen for lactoferrin (7%). In patients with acute infections of the CNS (n = 30) 67% had raised ECP levels with significantly higher levels (P less than 0.001) in those having bacterial infections. The ECP levels were significantly correlated (P less than 0.001) to the lactoferrin-levels in the whole infectious group. In patients with tumours (n = 25) raised levels of ECP were found in 67% of those with malignant and in 6% of those having benign tumours. This difference was statistically significant (P = 0.001). The ECP levels were closely related to those of lactoferrin (P less than 0.001) and albumin (P less than 0.005). Of the patients with multiple sclerosis (n = 19) 25% had raised ECP levels. This proportion was not significantly different from those having raised lactoferrin levels. In three patients extremely high ECP levels (70-455 micrograms/l) were found and a causal relationship between ECP and the brain tissue damage in these patients is suggested. In comparison with the neutrophil-related data the findings suggest a preferential involvement of eosinophils in some diseases affecting the central nervous system.

Adolescent↗

Studies on the phagocytic activity of the granulocytes in psoriasis and palmoplantar pustulosis.

A kinetic method was used to determine the rates of phagocytosis of IgG-coated and C3b-IgG-coated latex particles by neutrophil granulocytes from twenty patients with psoriasis and twenty with palmoplantar pustulosis (PPP). Patients with psoriasis showed a highly increased rate of uptake of IgG-coated particles. An increased rate was also observed in patients with PPP. These results indicate enhanced Fc-receptor function. In healthy controls the uptake rate of C3b-IgG-coated particles was at least 30% higher than that of particles coated with IgG alone. In nearly half of the patients in the psoriasis and PPP groups the uptake rate failed to increase in the normal way, indicating that C3b dysfunction is common in both psoriasis and PPP. In neither group was there any relationship between the rate of phagocytosis and the clinical severity of the disease.

Adolescent↗

The peroxidase activity and cellular content of granule proteins in PMN during pregnancy.

The cellular content of myeloperoxidase (MPO), chymotrypsin-like cationic protein (CCP) and lactoferrin (LF) of isolated polymorphonuclear leucocytes (PMNs) from pregnant women were analysed by immuno-chemical methods. The cellular levels of MPO and CCP were unaltered during pregnancy while the cellular levels of LF were increased during pregnancy and post partum (P less than 0.01). Peroxidase activity within isolated PMN was analysed by two methods, a Guaiacol method and a Chemiluminescence method. The activity was found to be reduced during pregnancy. The reduction was explained by the reduction in eosinophil peroxidase which in turn was a consequence of a reduced number of circulating eosinophils during pregnancy.

Adult↗

Partial characterization and identification of chemokinetic factors in serum.

The chemokinetic effect of serum, defined as the stimulation of the rate of polymorphonuclear neutrophil (PMN) migration in the presence of serum has been investigated for the purpose of identifying the major factors in serum contributing to this effect. The chemokinetic activity has been measured in fresh and heated (56 degrees C) serum and in fractions of serum separated by gel filtration. Gel filtration showed the existence of at least three heat-stable chemokinetic factors with approximate molecular weight of 800,000, 150,000, and 70,000. By immunoprecipitation and immunoadsorption the 800,000 mol. wt factor was identified as alpha 2-macroglobulin and the 70,000 mol wt. factor as alpha 1-antitrypsin and orosomucoid. Heat-labile chemokinetic activity was found in fractions representing mol. wts around 200,000 and 50,000. Immunoprecipitation and immunoadsorption indicated that these heat-labile chemokinetic factors were C3-associated. This investigation suggests a new functional role for the acute-phase reactants alpha 2-macroglobulin, alpha 1-antitrypsin, orosomucoid, and C3 in the modulation of PMN migration and also suggests that the chemokinetic activities of these substances are regulated by specific antagonists at various levels.

Cell Movement↗

Cellular origin of the chemokinetic inhibitor of polymorphononuclear leucocytes found in sera from patients with chronic lymphocytic leukaemia.

In a previous study, we demonstrated the existence in serum from patients with chronic lymphocytic leukaemia (CLL) of a cell-directed, heat-labile chemokinetic inhibitor of polymorphonuclear leucocytes (PMN). The aim of this investigation was to study the cellular origin of this inhibitor. Supernatants from short term cultured lymphocytes from 3 healthy persons and 5 patients with CLL, and from 16 different established human non-haematopoietic and haematopoietic cell lines were analyzed. Only the leukaemic B-lymphocytes from the CLL patients produced the inhibitor. The presence of the inhibitor was also demonstrated in supernatants from the fresh CLL cells from one CLL patient and a leukaemic cell line established from these cells using Epstein-Barr virus as the immortalizing agent. A lymphoblastoid cell line derived from the normal B-cells of the same CLL patient did not produce the chemokinetic inhibitor. We therefore conclude that the cellular origin of the heat-labile, cell-directed chemokinetic inhibitor of PMN migration is the CLL cell.

B-Lymphocytes↗

Granulocyte proteases in human maxillary sinus secretions.

Retained maxillary sinus secretions from 10 consecutive patients suffering from maxillary sinusitis were studied with regard to proteolytic activity and its possible sources. All secretions were proteolytically active. In 3 purulent secretions the proteolytic activity was of the same magnitude as that of a standard with an excess of pancreatic trypsin. The enzymes responsible for the proteolytical activity were found to be mainly of granulocyte origin, neutrophil elastase, unspecific collagenase and chymotrypsin-like cationic protein (CCP).

Adult↗

A fasting and vegetarian diet treatment trial on chronic inflammatory disorders.

Twenty patients with arthritis and various skin diseases were studied on a metabolic ward during a 2-week period of modified fast followed by a 3-week period of vegetarian diet. During fasting, arthralgia was less intense in many subjects. In some types of skin diseases (pustulosis palmaris et plantaris and atopic eczema) an improvement could be demonstrated during the fast. During the vegan diet, both signs and symptoms returned in most patients, with the exception of some patients with psoriasis who experienced an improvement. The concentrations of lactoferrin in serum reflect the turnover and activity of neutrophil leukocytes. When this protein was initially increased it fell to normal values in most cases. The improvement or impairment of signs and symptoms was related to the lactoferrin levels in serum.

Adult↗

Distinctive cationic proteins of the human eosinophil granule: major basic protein, eosinophil cationic protein, and eosinophil-derived neurotoxin.

The human eosinophil granule contains a number of cationic proteins that have been identified and purified to homogeneity, including the major basic protein (MBP), the eosinophil cationic protein (ECP), and the eosinophil-derived neurotoxin (EDN). Because of confusion in the literature regarding the distinctiveness of MBP and ECP, we investigated the immunochemical and physicochemical properties of these purified proteins by electrophoresis on sodium dodecyl sulfate-polyacrylamide gels (SDS-PAGE), by specific double antibody radioimmunoassays (RIA) for MBP and ECP, and by fractionation of acid-solubilized eosinophil granules on Sephadex G-50 columns. Analysis of a mixture of the three purified proteins by SDS-PAGE showed that they migrated as three distinct bands with differing m.w. Comparison by specific RIA for MBP and ECP did not demonstrate any appreciable immunochemical cross-reactivities among the three proteins. Sephadex G-50 column fractions of acid-solubilized eosinophil granules were analyzed by RIA and by SDS-PAGE analysis of individual column fractions. MBP, ECP, and EDN eluted at different volumes from Sephadex G-50 columns as determined by RIA and SDS-PAGE. Soluble extracts of eosinophil granules from patients with the hypereosinophilic syndrome contained between six and 64 times more MBP than ECP on a weight basis. These observations demonstrate that MBP, ECP, and EDN are distinctive cationic proteins of the human eosinophil granule and that eosinophil granules from patients with eosinophilia contain considerably greater quantities of MBP than ECP.

Binding, Competitive↗

Purification and characterization of a new cationic protein--eosinophil protein-X (EPX)--from granules of human eosinophils.

The isolation and characterization of a new eosinophil-derived protein, eosinophil protein X (EPX) is here described. The purified EPX is a highly basic glycoprotein and shows one band on sodium dodecyl sulphate polyacrylamide gel electrophoresis and on agarose electrophoresis. The molecular weight of the unreduced protein was 23,000 and after reduction 19,000. EPX did not precipitate antibodies prepared to other eosinophil-derived proteins such as eosinophil cationic protein (ECP) or major basic proteins (MBP) or antibodies prepared to a number of neutrophil-derived proteins. The eosinophil origin of EPX was indicated by the linear correlation between the amount of EPX and the percentage of eosinophils in mixed leucocyte extracts prepared from normal individuals. The EPX content was estimated to be on average 10 micrograms/10(6) normal eosinophils. EPX from normal eosinophils and from eosinophils from one patient with hypereosinophilia seemed to be identical.

Amino Acids↗

The effect of hyaluronic acid on neutrophil function in vitro and in vivo.

HA affects neutrophil function both in vitro and in vivo at picomolar concentrations. The present data suggest that the activity of HA is directed against some very basic metabolic mechanisms in the cell involving the increased synthesis of ATP and increased glucose metabolization. A preliminary clinical trial suggests that subcutaneous injections of HA may be used in the therapy of patients with undue susceptibility to bacterial infections but firm conclusions as to this point has to await regular controlled clinical trials.

Chemotaxis, Leukocyte↗

Lactoferrin, lysozyme, and beta 2-microglobulin levels in cerebrospinal fluid: differential indices of CNS inflammation.

The CSF levels of lactoferrin, lysozyme, and beta 2-microglobulin (beta 2 mu) were measured in patients with evident, probable, or possible inflammatory CNS reactions and compared to those found in neurologically apparently healthy patients. Patients with viral CNS infections had significantly raised beta 2 mu and lysozyme levels but normal lactoferrin levels, indicating a local activation of lymphocytes and monocytes but not of granulocytes. Patients with bacterial CNS infections had significantly raised levels of all three cell markers, but the increase of lysozyme and lactoferrin was relatively more pronounced than that of beta 2 mu, indicating that the inflammatory response to bacterial agents is dominated by monocytes and granulocytes. Patients with primary or secondary malignant brain tumors were characterized by a moderate increase of beta 2 mu and a considerable increase in both lysozyme and lactoferrin, i.e., the same protein pattern as observed in bacterial CNS infection. The lysozyme levels were moderately increased in half the patients with benign cerebral tumors while the levels of beta 2 mu and lactoferrin were normal, indicating that benign and malignant brain tumors induce different local inflammatory CNS reactions. Half the patients with pituitary gland adenoma had elevated beta 2 mu and lysozyme levels but normal lactoferrin levels, suggesting that immunological mechanisms are associated with the adenoma development. Patients with MS had moderately but significantly raised CSF levels of beta 2 mu and lysozyme and a third of them also had raised levels of lactoferrin, a protein pattern suggesting a low-active inflammatory process in CNS involving mononuclears and granulocytes. A similar protein pattern was found in Guillain-Barré syndrome. In cerebrosarcoidosis we noted considerably increased lysozyme and beta 2 mu but normal lactoferrin levels, consistent with the idea that the sarcoid granuloma mass is dominated by monocytic inflammatory cells. The data obtained indicate a clinical value of lactoferrin, lysozyme, and beta 2 mu as differential indices of inflammatory cell reactions taking place in various CNS processes.

Adult↗

The Gordon phenomenon induced by the eosinophil cationic protein and eosinophil protein X.

Cerebellar Purkinje cell degeneration after intracerebral injection of eosinophil granulocytes or extracts thereof is known as the Gordon phenomenon. The reaction is said to be highly selective. An eosinophil-derived neurotoxin (EDN) has recently been reported to induce the Gordon phenomenon. However, we report here that two eosinophil-derived proteins, eosinophil cationic protein (ECP) and eosinophil protein X (EPX), may induce the Gordon phenomenon after intraventricular injection. The potency of ECP is far greater than that of EPX and the latter is possibly identical to EDN. The Fink-Heimer staining for degenerating nerve fibers and boutons, however, indicated that the selectivity of the Gordon phenomenon is not as specific as was previously thought, since this method revealed degeneration of all brain areas in proximity to the ventricular system.

Animals↗

Indices of inflammatory cell activity and pulmonary function in different stages of sarcoidosis.

The present study was carried out to compare radiological and physiological changes in sarcoidosis with biochemical markers for inflammatory cell populations. Of 53 patients with sarcoidosis, 28 had respiratory symptoms and 30 past or present bilateral hilar adenopathy without symptoms. A clinical score based on lung function tests and radiological findings correlated well with elevations of lysozyme and beta2-microglobulin in serum, indicating increased inflammatory cell activity in patients with more severe lung affection. A covariation between beta2-microglobulin and lysozyme was found, suggesting concomitant activation of macrophages and lymphocytes in sarcoidosis. Serum levels of lactoferrin were elevated in patients with a disease of short duration but did not correlate with the severity of the lung affection. The closing volume also seems to be abnormal in the early course of the disease, while elevated lysozyme and beta2-microglobulin levels rather seem to reflect the extent of the pulmonary affection.

Adult↗

Identification of a chemokinetic inhibitor in serum from patients with chronic lymphocytic leukaemia.

The effects of serum from patients with chronic lymphocytic leukaemia (CCL) on normal polymorphonuclear leucocyte migration (PMN) were examined by means of the leading front technique, using a modified Boyden chamber. 18 randomly selected patients were studied. 13 patients had a reduced chemokinetic activity. The defective migration was explained by the finding in serum from these patients of cell-directed inhibitory activity which was destroyed by heating (56 degrees C, 30 min). The B-lymphocytes as the origin of the inhibitory activity was suggested by the presence of a similar activity in supernatants from cultured tumour cells. 6 of the 18 patients had the combination of a defective chemokinetic activity and low levels of immunoglobulins. These 6 patients had an increased tendency towards infections.

Aged↗

Neutrophil and eosinophil degranulation during hemodialysis are mediated by the dialysis membrane.

During hemodialysis of heparinized blood without having a patient in the circuit, the serum concentrations of lactoferrin, myeloperoxidase (MPO) and eosinophil cationic protein (ECP) steadily increased, indicating neutrophil and eosinophil degranulation. The increments in serum of these granular proteins were more pronounced using plate dialyzers than capillary dialyzers. The release of granule constituents does not seem to reflect merely a sequestration of granulocytes in the dialyzer, since the increase of the serum concentrations of lactic dehydrogenase was very modest. The intracellular contents of lactoferrin, MPO, lysozyme and ECP were reduced after experimental dialysis in the granulocytes isolated from the blood, indicating that the cells in association with degranulation were not entrapped in the dialyzer. The relatively modest increase of the plasma concentrations of lysozyme during experimental hemodialysis, in spite of the reduction of the intracellular content of lysozyme, was explained by the propensity of lysozyme for adhering to the dialysis membrane. Serum samples obtained at different times during dialysis did not induce an enhanced release of granular proteins from isolated granulocytes in vitro. The earlier observed increase during hemodialysis of the serum concentrations of granular proteins in uremic patients can be explained by the dialysis membrane triggering granulocytes to degranulate.

Blood Proteins↗