PubMed Health⌕ Search

Biomedical subjects

J Csongor

Publications and source records attributed to J Csongor.

At least 19 recordsLinked to original sources

Serum complement activation of SLE patients during plasmapheresis.

The erythrocyte complement receptor 1 (ECR1)-immune complex binding assay is a sensitive method for the determination of complement fragments which can be activated by bovine serum albumin (BSA)-anti-BSA in vitro. When the C3b/C4b containing bovine serum albumin (BSA)-anti-BSA was formed in the presence of the serum of patients with systemic lupus erythematosus (SLE) its binding to ECR1 was found to be lower than that formed in sera of normal volunteers. The plasmapheresis of SLE patients homozygous for the CR1/E high density allele displays a beneficial effect on the formation of C3b/C4b containing BSA-anti-BSA and its binding to ECR1. There was no significant correlation between the serum C3/C4 level and the percentage of C3b/C4b containing BSA-anti-BSA binding to the ECR1 of SLE patients during plasmapheresis. At the same time, there was an inverse correlation between the serum immune complex level and the ECR1 binding, which was significant in 3 of 5 cases. These data suggest that, besides the determination of different components of complement activation, the functional assay of complement activation might be useful in monitoring the effect of plasmapheresis in SLE.

Adult↗

The mechanism of inhibitory effect of eicosapentaenoic acid on phagocytic activity and chemotaxis of human neutrophil granulocytes.

Free eicosapentaenoic acid (EPA) was found to inhibit dose dependently the chemiluminescence of human neutrophil granulocytes phagocytosing zymosan and their chemotaxis induced by C5a-containing zymosan-activated serum (ZAS) and platelet-activating factor. Rigidification of plasma membranes in the ZAS-treated cells could be observed by measuring the fluorescence anisotropy. The cells were labeled by 3-[p-(6-phenyl-1,3,5-hexatrienoil) phenyl] propionic acid, reporting plasma membrane for determination of membrane fluidity. In resting, nonstimulated neutrophils, EPA dose dependently increased the fluidity of plasma membrane. In zymosan-activated cells, however, after a short fluidization, the basic effect of EPA was a rigidification compared to very low fluorescence anisotropy values of activated control cells. This diminished fluidity, increased membrane stability of plasma membranes can be one of the reasons for the decreased functions (phagocytosis and chemotaxis) of human EPA-treated neutrophils.

Cell Membrane↗

Characteristics of stretch-release induced tension development in arterial smooth muscle.

Stretching helical strips of porcine a. carotis comm. to 1.7 times the resting length increases myosin light chain phosphorylation from 0.22 to 0.67 mol phosphate/mol light chain. While stretch is maintained, the stretch induced light chain phosphorylation decreases and reaches the resting level over a period of 60 minutes. The fully stretched arterial strips containing maximally phosphorylated myosin light chain cannot generate active tension which indicates, according to the sliding filament theory, the lack of overlap between actin and myosin filaments. When stretch is released from these muscle strips active tension develops. The amplitude of this stretch-release induced tension depends on the level of myosin light chain phosphorylation related to the time interval between stretch and release as well as on the extent of the overlap zone related to the length of the released strip. Three-dimensional graphic representation of both measured and interpolated data points in an active tension-light chain phosphorylation-muscle length space reveals a contractility surface which demonstrates that active tension appears as a sigmoidal function of light chain phosphorylation, on the one hand and shows maximum as a function of muscle length, on the other hand.

Animals↗

Candidacidal mechanisms in the human neonate. Impaired IFN-gamma activation of macrophages in newborn infants.

We studied the interaction between Candida albicans and mononuclear phagocytes derived from cord blood. In the presence of normal serum, the extent of phagocytosis and killing of candida by monocyte-derived macrophages was equivalent for newborns and adults. In the absence of serum both phagocytosis and killing by macrophages were reduced by half, but cord and adult cells were still equivalent. Mannosylated BSA and mannan inhibited ingestion of unopsonized candida by macrophages, suggesting a role for the mannose receptor. Exposure of cord and adult macrophages to IFN-gamma (10-500 U/ml) gave quantitatively different results in Candida killing, as well as in release of superoxide anion (O2-). Maximal increase in these functions with adult macrophages was achieved with 100 U/ml IFN-gamma. No enhancement with cord macrophages could be detected after treatment with 100 U/ml, and at 500 U/ml there was still significantly lower killing and O2- release compared with adult cells. Defective up-regulation of O2- release was also present in cord monocytes exposed to IFN-gamma on day 0. Studies of the surface expression of IFN-gamma receptors using a "nonblocking" mAb against the IFN-gamma receptor revealed a comparable number of receptors on cord and adult monocytes. When blocking Abs were used, however, there was a three times higher number of positive cells in cord monocytes. Specific binding of 125I-IFN-gamma to cord monocytes and macrophages was also higher compared with adult cells. These data suggest that neonatal macrophages have a normal capacity to ingest and kill both opsonized and unopsonized Candida but cannot be fully activated by IFN-gamma, a finding that could not be attributed to lower expression of IFN-gamma receptors on the neonatal cells.

Adult↗

Age-dependent alterations of human recombinant GM-CSF effects on human granulocytes.

The granulocyte-macrophage colony stimulating factor (GM-CSF) is an important in vivo regulator of granulopoiesis and neutrophil functions. It is well-known that the immune response and the transmembrane signalling in immune cells change with aging. We wished to elucidate the effects of GM-CSF in itself and in priming the activities of other inflammatory agents on neutrophils of elderly persons. Neutrophils of 20 healthy elderly (aged 60-90 years) and 20 healthy young (aged 20-25 years) subjects were studied for superoxide anion production, intracellular free calcium mobilization, antibody dependent cellular cytotoxicity (ADCC) and intracellular killing activities. It was found that GM-CSF is unable to prime neutrophils of elderly subjects to the action of FMLP, metenkephalin or opsonized zymosan. By the use of Pertussis toxin and H7 it was demonstrated that a different signal transduction pathway in neutrophils of elderly subjects is activated by GM-CSF or FMLP if compared to that of young subjects. These results suggest that the lack of priming could contribute to the greater susceptibility of the elderly to infections and that the change of the signal transduction mechanism in neutrophils of elderly subjects might partly explain this phenomenon.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Transmembrane signaling changes with aging.

Altered immune response and transmembrane signaling with aging has previously been demonstrated. The aim of the present study was to characterize PMNLs and lymphocyte G proteins and to determine whether their relative amounts are altered with aging. First we studied the effects of FMLP on PMNLs IP3 formation. It was found that in any group of elderly the PMNLs IP3 formation was significantly decreased compared to that of young subjects. In FMLP receptor binding affinity no measurable difference exists in either low- or high-affinity FMLP receptors. The autoradiogram of 32P-ADP-ribosylated proteins by CT in lymphocytes of young individuals showed a major polypeptide of 40 kDa, and two much less prevalent components of 52 and 45 kDa. In contrast, in lymphocytes of elderly subjects the major polypeptide was 45 kDa, and the two others were very weakly labeled. In PMNLs, CT labeled the 45-kDa band quite strongly, mainly in the elderly, and the 52- and 40-kDa bands were very weakly labeled, mainly in young subjects. When PT was used, no age-related pattern changes could be demonstrated, while differences could be observed between the two types of cells.

Adenosine Diphosphate Ribose↗

Body composition in hypertensive elderly and middle-aged patients.

The occurrence of hypertension, leading to various life-threatening complications in the elderly is a widely recognized problem. The changes of body composition were determined in 120 control and untreated hypertensive subjects of various ages. In middle-aged hypertensive males, the total blood volume and plasma volume increased significantly compared to those of the healthy controls, while this increase was not significant in the case of hypertensive middle-aged females. In contrast, in the elderly hypertensive male subjects, the volume of all fluid components decreased, except the total body fat and the vascular volumes. There was a slight, statistically non-significant, increase in all the vascular volumes except in the red cell mass. The elderly hypertensive females showed the same tendency compared to the healthy controls of the same age. The vascular compartments seem to be decreased in elderly males, compared to those of the middle-aged males, while slightly increased in elderly females.

Adipose Tissue↗

Altered phosphatidylinositol breakdown after K-elastin stimulation in PMNLs of elderly.

The degradation of elastic fibres during atherosclerotic plaque formation in arterial wall is a well known process. The liberated elastin peptides such as K-elastin possess various biological activities: They are chemotactic for monocytes and fibroblasts, stimulate the oxidative burst and the intracellular free Ca2+ mobilisation through the phosphatidylinositol (PIP2) breakdown in PMNLs. It was found that the PIP2 breakdown induced by K-elastin is a pertussis toxin sensitive process in PMNLs of young subjects. In the case of the elderly, the K-elastin-induced oxidative burst, intracellular free Ca2+ elevation was less than in young, and could not be inhibited by pertussis toxin. Studying the K-elastin-induced inositol phosphate (IP) formation in PMNLs of elderly a disturbed PIP2 breakdown was found. K-elastin stimulated the IP formation at a very low level in PMNLs of elderly. This alteration of the second messenger formation (e.g. IP3 and Ca2+) after KE stimulation, might be the consequence of their originally elevated levels in resting PMNLs of elderly.

Age Factors↗

Complement-mediated immune complex solubilization and precipitation inhibition in sera of patients with non-Hodgkin's lymphoma.

The complement functions of 42 patients with non-Hodgkin's lymphoma have been examined. The patients were divided into groups according to the severity of their disease: 1st--patients with high-grade lymphomas, 2nd--with low-grade lymphomas and 3rd--with chronic lymphocytic leukaemia. The adopted methods were the measurements of complement-mediated immune complex solubilizing capacity (CMSC) and the complement-mediated immune complex precipitation inhibition capacity (IPIC). The CMSC and IPIC values were examined parallel with CH50, C3 complement levels and with levels of circulating immune complexes (CIC) in the sera of patients. The results indicated that the acquired deficiency of complement functions could be established by CMSC and IPIC measurements in the sera of patients with high-grade lymphomas. These defects were found to be milder in the group with low-grade lymphomas, and were not detectable in CLL. The changes of CH50 levels were found to be similar to that of IPIC values and the decrease in C3 levels was detectable in high-grade and low-grade lymphomas too. Elevated CIC levels were found in those cases in which both CMSC and IPIC were decreased.

Antigen-Antibody Complex↗

Age related impairment in phosphatidylinositol breakdown of polymorphonuclear granulocytes.

It is well known that with aging the immune response decreases. Most of the effector functions occur through specific receptors. Thus, we investigated the effects of various stimulants, acting through receptors or directly through the GTP-binding Gi protein, on phosphatidylinositol breakdown in PMNLs of young and elderly subjects and try to modulate it. A marked decrease in inositol phosphate (IP1, IP2, IP3) formation in PMNLs of elderly was found under FMLP stimulation when compared to that of young subjects. Neither GTP gamma S, nor AIF4- could induce an increase of IP3 in PMNLs of elderly comparable to that of young subjects. The results suggest that at least an alteration exists at the GTP-binding Gi protein level, as well as in the mechanism of linkage of the receptor to the G protein.

Adult↗

Immunobiological methods in the prenatal diagnosis and evaluation of foetal neural tube defects.

In cases of foetal neural tube defects (NTDs) macrophages are present in the amniotic fluid. These mononuclear cells were analysed with immunobiological methods: functional markers as Fc and C3b receptor-mediated phagocytosis and chemoluminescence have been studied. It was found that most of these pathognomic cells ingest haemolysin sensitized sheep red blood cells (sSRBCs) and zymosan (Mannozym) particles opsonized with fresh human serum. Amniotic fluid cell suspensions from pregnancies with and without foetal NTDs were stimulated by opsonized Mannozym; consistently higher chemoluminescence activities were found when open lesion was present. The evaluation of multiple functional markers is likely to provide a better basis for understanding the characteristics of amniotic fluid macrophages and may contribute to the prenatal diagnosis of NTDs.

Amniocentesis↗

Effects of herpesvirus infections on the chemiluminescence induced by zymosan phagocytosis in mouse peritoneal macrophages.

The chemiluminescence (CL) induced by zymosan phagocytosis was tested in mouse peritoneal macrophages infected with three different types of herpes viruses: herpes simplex type-1 (HSV-1), human cytomegalovirus (HCMV) and murine cytomegalovirus (MCMV). The intensity of CL was tested in various intervals of virus infections. In the first eight hours zymosan induced chemiluminescence decreased in all the three systems. By the 24th hour, the macrophages infected with HCMV had almost completely recovered from the early defect, while in the macrophages infected with both HSV-1 and MCMV, the chemiluminescence induced by zymosan remained impaired.

Animals↗

Defective immune complex degradation by monocytes in patients with systemic lupus erythematosus.

The binding of 125I-labelled anti-bovine serum albumin (BSA)-BSA immune complexes (IC), giving a final molar antibody to antigen ratio of 1:1, to monocytes isolated from 18 patients with systemic lupus erythematosus (SLE) and from 10 normal healthy donors was quantitatively investigated. The degradation of the bound IC by the same monocytes was kinetically determined at the same time. The assays were performed on monocyte monolayers. Scatchard plots at 4 degrees C demonstrated that monocytes from patients with active SLE expressed a mean Fc gamma receptor (FcR) number that was 22% higher than that of the controls, although this did not reach statistical significance. The FcR number of normal monocytes and the degradation rate of anti-BSA-BSA complexes by the same cells showed a positive correlation. At the same time, the digestion of anti-BSA-BSA complexes by monocytes of SLE patients with active disease was prolonged, despite their enhanced FcR-ligand binding. The dissociation of FcR-ligand binding and FcR-mediated degradation suggests that the IC degradation is controlled by altered biochemical mechanisms in the monocytes of SLE patients.

Antigen-Antibody Complex↗

Effect of mannozym on the chemiluminescence of phagocytes.

Mannozym (zymosan) induces chemiluminescence (CL) in human neutrophils, monocytes and in the cells of C4M phi murine macrophage cell line. The CL enhancing effect of Mannozym opsonized in human serum is higher than that of non-opsonized material. This may be due to the capacity of Mannozym to bind complement components and immunoglobulins from serum and to activate the phagocytes via their C3b and Fc receptors. Besides, Mannozym can be phagocytosed both in opsonized and non-opsonized forms.

Animals↗

Effect of lentinan on the chemiluminescence produced by human neutrophils and the murine macrophage cell line C4M phi.

Lentinan, an immunopotentiating polysaccharide, stimulates the production of chemiluminescence (CL) by human neutrophils and the murine macrophage cell line C4M phi. The CL enhancing effect of lentinan opsonized in human serum is greater than that of lentinan itself. Lentinan's stimulation of neutrophil CL was increased by 1/2 when opsonized in human serum inactivated at 56 degrees C to remove complement, while the CL was increased two fold by lentinan opsonized in whole serum. This indicates that C3b and immunoglobulin contribute separate signals in the activation process mediated by opsonized lentinan. The distinct roles of the C3b and Fc receptors was further illuminated by the finding that an Fc receptor-negative cell line was unresponsive to lentinan opsonized in heat inactivated serum (56 degrees C), whereas it exhibited a five fold increase in CL in response to lentinan opsonized in serum containing complement. Lentinan in an opsonized form can stimulate the production of CL via C3b and Fc receptors. This mechanism may be considered as one mode of action of lentinan and other similar immunopotentiating and antitumour glucan-type polysaccharides.

Animals↗

Body composition in elderly people. I. Determination of body composition by multiisotope method and the elimination kinetics of these isotopes in healthy elderly subjects.

The body composition of 40 healthy elderly and 20 healthy young subjects was determined and compared. It was found that the age-related changes were more marked in females than in males. Total body water was decreased as a consequence of diminished lean body mass. Extracellular fluid volume remained unchanged, while plasma volume increased. Thus, the liquid components of lean body mass were redistributed between the intracellular and extracellular spaces. The elimination kinetics of isotopes were not significantly different between young and aged subjects, except the elimination of radiosulfate.

Aged↗

Body composition in elderly people. II. Comparison of measured and predicted body composition in healthy elderly subjects.

The predictive values of the equations of Moore et al. and Hume and Weyers and the measured values of body composition were compared in healthy, carefully selected aged and young subjects of both sexes. In the case of young subjects, these prediction equations seem to be adequate, even if this could not be affirmed with certainty by our results. The equations of Moore et al. were found not to be adequate for elderly males, while they were only suitable for the determination of intracellular components in elderly females.

Adult↗

Inhibition of anaphylaxis by inactivated lymphocyte clone with radiolabelled antigen.

125I-labelled ovalbumin (OVA) antigen did not sensitize guinea-pigs and anaphylaxis did not develop after native OVA challenge. The radiolabelled antigen was fixed by lymphocytes with highly specific receptors for 125I-OVA and this condition produced a continuous radiation damage leading to inactivation of the cells. As the proliferative response of lymphocytes did not occur, no antibody production was detected. This was demonstrated by passive haemagglutination techniques. However, the immune response to a simultaneously given non-radioactive antigen remained intact. It is supposed that radiation damage depended on specific activity of antigen destroying the antigen-specific lymphocyte clone selectively. The mechanism and the practical importance of the in vivo 'antigen suicide' is discussed.

Anaphylaxis↗