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Biomedical subjects

I Brandslund

Publications and source records attributed to I Brandslund.

At least 73 records · Page 4Linked to original sources
PubMed1984

In vitro investigations of human immunoglobulin preparations: Fc-receptor reactivity and complement consumption.

The complement consuming activity and monocyte Fc-receptor (FcR) binding of some commercial IgG-preparations for intravenous (i.v.) and intramuscular (i.m.) use was investigated. A pepsin-treated IgG-preparation for i.v. use exhibited no detectable complement consuming activity and impaired FcR binding, whereas an unmodified IgG preparation had no detectable complement consuming activity, but retained full FcR binding. A preparation prepared by PEG-precipitation and ion-exchange chromatography exhibited low complement consuming activity as well as good FcR binding. Three preparations for i.m. use showed moderate to strong complement consuming activity, whereas only one of these preparations retained full FcR binding.

Complement Activation↗
PubMed1984

Association of circulating immune complexes with glomerular proteinuria in patients with transitional cell carcinoma of the urinary bladder.

The presence of circulating immune complexes and the correlation between the amount of immune complexes and glomerular proteinuria was studied in 20 patients with urothelial bladder tumors followed by cystoscopies for 6-18 months. Circulating immune complexes, measured by the PEG-CC, PICRIA and C1q-ELISA assays, occurred more frequently in cases with residual or recurrent tumors than without tumors, and most frequently in cases with large tumors and a high grade of malignancy. Glomerular proteinuria, defined as the increased relative clearance of albumin, transferrin and haptoglobin, occurred in almost all cases with increased immune complex concentrations. Both glomerular proteinuria and the severity of proteinuria was significantly related to the immune complex concentration.

Adult↗
PubMed1984

Development and clinical application of electroimmunoassays for the direct quantification of the complement C3 split products C3c and C3d.

The present report describes the development of electroimmunoassays for the direct quantification of C3d and C3c, split products of the third complement factor (C3). Both methods were developed as rocket immunoelectrophoreses, using two antibody preparations with specificities against the C and D epitopes on C3. A stable calibrator preparation for C3c and C3d was produced by autolytic cleavage of C3. Investigations of patients with anaphylactic reactions or chronic immunological disorders showed that quantification of C3c and C3d in plasma by these methods reflected the degree and rate of complement activation. C3d determination was found to be the most sensitive and reliable indicator of C activation, both during acute and chronic activation since C3c is eliminated considerably faster from the circulation than C3d (estimated half lives of 2 h and 4 h, respectively). Treatment of rheumatoid arthritis patients with prednisolone caused a prompt decrease of plasma C3d values, indicating that the clinical effect may be due to inhibition of complement activation.

Antibody Specificity↗
PubMed1984

Lack of effect of tranexamic acid on rheumatoid arthritis.

In a double-blind controlled study on 45 rheumatoid arthritis patients, no effect of tranexamic acid (Cyklocapron, 4.5 g per day for 6 weeks) was found in terms of subjective or objective parameters of disease activity. Tranexamic acid did not reduce complement activation, measured by plasma concentrations of the complement C3 split product C3d. Immune complex concentrations in serum were also unaffected. We conclude that plasmin inhibitors do not reduce immune complex mediated complement activation, and they should not be used for treatment of rheumatoid arthritis.

Adult↗
PubMed1984

Solubilization of immune complexes in complement factor deficient sera and the influence of temperature, ionic strength and divalent cations on the solubilization reaction.

The complement-mediated solubilization (CMS) of immune complexes (IC) and the initial kinetics (IKS) of this reaction in human sera depleted of or deficient in C2, C3, C8, factors B, P and I were investigated. Sera depleted of B or P and those lacking native C3 or factor I showed virtually no CMS whereas the IKS and CMS capacity of a C8-deficient serum were within the reference range. The IKS of a C2-deficient serum was markedly retarded while the CMS capacity was normal. Addition of C2 normalized the kinetics of the reaction. There was a good correlation between the kinetics of CMS determined by a radioassay and kinetic data for the binding of C3b to preformed immune complexes. The CMS capacity reached maximum at 39-41 degrees C and at an ionic strength of approximately 0.20 mu. Selective chelation of Mg2+ completely abolished the CMS of IC. Maximal CMS was observed at Mg2+ concentration of about 2mM. Chelation of Ca2+ in serum by Mg2+-ethylene glycol tetraacetic acid reduced the CMS capacity by up to 50% and the IKS was markedly retarded. Varying the Zn2+ or Mn2+ ion concentrations in serum influenced neither the IKS nor the CMS capacity.

Antigen-Antibody Complex↗
PubMed1983

Simultaneous quantitation of free haptoglobin and haemoglobin-haptoglobin (HbHp) complexes by double-decker rocket immunoelectrophoresis.

Existing immunochemical methods for haptoglobin (Hp) determination are incapable of distinguishing between free haptoglobin and haemoglobin-haptoglobin (HbHp) complexes. A one-dimensional double-decker rocket immunoelectrophoretic method (DD-RIE) for simultaneous quantitation of free Hp and Hp bound as HbHp complexes was therefore developed. The DD-RIE can be used for quantitative in vitro studies of the Hb-Hp interactions, for quantitation of Hp's Hb binding capacity and for investigations of haemolytic episodes in patients. The clinical value of the method is illustrated by an investigation of a patient with a gradual accumulation of HbHp complexes in plasma, a steady rise in total Hp and a fall in free Hp during haemolysis. A proposed receptor-mediated clearance of the complexes by the reticuloendothelial system (RES) could not be substantiated, as HbHp receptors were not demonstrable on human blood monocytes.

Haptoglobins↗
PubMed1983

A standardized method for quantitating the complement-mediated immune complex solubilizing capacity of human serum.

A standardized radioassay for measuring the complement-mediated immune complex solubilizing capacity (CMSC) and the initial kinetics of the solubilization (IKS) reaction is described. The total complement (C)-mediated solubilizing capacity was determined after incubation of diluted serum and 125I-BSA-anti-BSA. Percentage C-mediated solubilization (CMS) was measured after centrifugation by determining the distribution of radioactivity. The dependency of CMSC upon factors such as serum dilution and buffer system used, amount of IC added to serum, serum storage conditions and centrifugation conditions was investigated in order to optimize the assay. The CVt of the standardized assay was 0.10-0.17 depending upon the CMSC level measured. Treatment which inactivates C factors (heating), interferes with C activation (EDTA) or activates and consumes C components (zymosan) markedly reduces the CMSC. Preliminary investigation of pathological sera showed that both IKS and CMSC were clearly reduced in SLE sera. By contrast, rheumatoid arthritis sera exhibited normal IKS and only marginal reduction in CMSC.

Adolescent↗
PubMed1983

High serum beta-2-microglobulin levels and circulating immune complexes containing beta 2m and anti-beta 2m antibodies in Felty's syndrome.

Serum beta-2-microglobulin (beta 2m) levels, incidence and levels of anti-beta 2m autoantibodies, and quantity of circulating macromolecular complexes containing beta 2m were studied in patients with Felty's syndrome (FS), joint-restricted rheumatoid arthritis (RA), and healthy controls. The serum beta 2m concentrations detected in the FS group (6.95 +/- 2.9 mg/liter) greatly exceeded those of the RA group (3.4 +/- 1.2 mg/liter) and the control group (1.42 +/- 0.69 mg/liter). Autoantibodies to beta 2m were frequent in the FS group. Circulating complexes containing beta 2m, prepared by precipitation in 3% polyethylene glycol, were detected in 65% of FS and 35% of RA patients. In the majority of these cases the solid-phase C1q purified immune complexes also contained beta 2m. Detection of anti-beta 2m antibodies in a significant part of complexes containing beta 2m suggests the presence of specific immune complexes in this fraction of FS and RA patients.

Antibodies↗
PubMed1983

The normal occurrence of two molecular forms of the eight complement component (C8) and their concentrations in a family with C8 deficiency.

A haemolytically inactive alpha-mobile complement C8 component was identified by crossed immunoelectrophoresis in a 27-year-old male with recurrent meningococcal infections and absence of complement mediated serum haemolytic activity. The patient's serum/plasma contained no demonstrable normal C8. C8 inhibitor activity was not demonstrable in his serum and the alternative activation pathway appeared to be intact. Serum from the proband's parents and both siblings had normal total haemolytic complement activity and they were without symptoms. However, both the normal and the haemolytically inactive C8 protein were demonstrable in their sera. Their normal C8 concentrations were less than one-half of the normal C8 mean value and distinctly below the lowest value found in ten healthy persons. The concentration of the inactive C8 component in the proband's serum was roughly 1 . 5 times higher than that of the other family members, whereas its concentration in sera of the family members was between 1 . 8 and 2 . 5 times the highest concentration found in ten healthy donors, all of whom also had an alpha-mobile C8 in measurable quantities.

Adult↗
PubMed1983

Normal bactericidal capacity against Neisseria meningitidis in serum from a patient with a hemolytically inactive complement factor 8 (C8).

The bactericidal capacity of serum against Neisseria meningitidis from a 27-year-old male with two episodes of meningococcal meningitis and C8 deficiency was compared to that of normal human serum (NHS) without demonstrable antibodies against Neisseria. The in vitro bactericidal capacity of the patient serum was found to be equal to that of NHS. Incubation of both sera at 56 degrees C for 30 minutes abolished the bactericidal effect. Rocket-immunoelectrophoresis analysis of molecules immunochemically identifiable as C8 revealed no consumption of these molecules in any of the sera in the bactericidal assay. No hemolytic complement activity was found in the patient serum, whereas the donor serum had normal total hemolytic complement activity with significant consumption of C8.

Adult↗
PubMed1983

Activation of the complement system and accumulation of hemoglobin-haptoglobin complexes in plasma during an adverse reaction to penicillin treatment.

A patient treated with penicillin intravenously developed a serum sickness-like reaction. Classical pathway complement (C) activation was indicated by quantitation of the split products C3c and C3d as well as demonstration of C4 conversion. Circulating immune complexes could, however, not be detected by the solid-phase Clq and PEG-precipitation methods. A concomitant accumulation of circulating hemoglobin-haptoglobin complexes and a marked fall in serum-fibronectin concentrations suggested saturation of the reticuloendothelial system. The plasma became a deep-red color, and a diffuse intravascular coagulation followed. The patient recovered completely upon discontinuation of penicillin administration.

Antigen-Antibody Complex↗
PubMed1983

Heterogeneity in electrophoretic mobility of C3-derived molecules expressing D but not C-epitopes following in vivo activation of the complement system.

Four different populations of C3-derived molecules expressing D but not C epitopes were identified following in vivo activation of the complement system. The four molecular forms, differing in electrophoretic migration velocity, were assigned the nos. 1, 2, 3 and 4 after decreasing electrophoretic mobility. Analysis of the time-dependent changes in the relative concentration of the different molecular forms demonstrated an increase in the plasma concentration of population 4 and a decrease of populations 2 and 3, whereas form 1 remained rather constant after acute activation of the complement system.

Animals↗
PubMed1983

Partial characterization of physiologically generated C3 components expressing C3d but not C3c epitopes.

Techniques for the quantification of C3d are shown to estimate the sum of 4 different plasma protein components possessing C3d but not C3c epitopes. All 4 components were C3-derived polypeptides as shown by activating serum containing 125I-labelled C3, isolating the anti-C3d reactive material in 14% PEG supernatant, followed by analysis on SDS-PAGE and autoradiography. Identical results were obtained by radiolabelling 14% PEG plasma supernatants followed by analysis of the anti-C3d reactive material. The components are referred to as d1, d1', d2 and d3 based on their relative electrophoretic mobilities (alpha 1, alpha 1, alpha 2 and alpha 2 respectively) judged by crossed immunoelectrophoresis. Their apparent molecular weights by SDS-PAGE were 129K (d1), 110K (d1'), 46K (d3) and 45K (d2). The possibility that one or more of the C3d containing components represented a complex of a C3 fragment with another plasma protein was investigated. The role of these components in the scheme of the physiological breakdown of C3 and the importance of the individual C3d components as indicators of complement activation in clinical materials is discussed. It is proposed that the 45K d2 component represents a final physiological breakdown product of C3 in human serum.

Antigen-Antibody Reactions↗
PubMed1983

Comparison of different assays for circulating immune complexes in age matched vasectomized and non-vasectomized men.

Sera from 46 men vasectomized for 5 yr and from 46 age-matched nonvasectomized men had previously been analyzed for circulating immune complexes (CICs) by four assays. Four additional CIC assays have now been performed on these sera: three Raji cell enzyme-linked immunosorbent assays (ELISAs) using alkaline phosphatase-conjugated antihuman IgG, IgA or C3 and the bull sperm ELISA. No significant differences in CIC levels were detected between the two groups using any of the assays. Results for two different sera obtained from 16 men 4 1/2 months apart correlated significantly for six of seven CIC assays evaluated in this way. In the bull sperm and Raji cell ELISAs, utilizing anti-IgG in the detection layer, the vasectomized men with sperm-agglutinating antibodies were found to have significantly higher CIC levels than those without sperm agglutinants. No association was found between the presence of sperm protamine antibody and levels of CICs. Since the vasectomized and control groups did not differ with respect to levels of CICs, immunoglobulins, or the complement C3 split product C3d, all 92 samples were combined into one group for further analysis. Serum IgG levels significantly correlated with the CIC levels in four of five CIC assays involving binding of IgG; IgA levels correlated with CIC determinations in the Raji-IgA assay, while plasma C3d levels correlated with the Raji-C3, the Raji-IgA, and the C1q-protein A binding assays. IgM levels did not correlate with activity in any assay. Finally, the degree of correlation between all eight CIC assays was determined, and significant positive correlations between assays were found in ten of twenty-eight comparisons.

Adult↗
PubMed1983

Complement activation in shock associated with a surgically provoked bacteriaemia.

The activation of complement (C) factors in a patient exhibiting an anaphylactoid shock 10 min after the initiation of transurethral coagulation of vesical papillomas was studied. Streptococcus faecalis was cultured from he urine before and after the shock and from the blood on two occasions within 2 days after the shock. The shock was associated with a marked but transient complement activation as judged from serial determinations of C3d and C3c by doubledecker rocket immuno electrophoresis and native C3 and C3c by crossed immuno electrophoresis. Conventional total C3 quantitation by rocket immuno electrophoresis did not reveal the activation. A decrease of native C4 to 20% of normal values and the appearance of C4 split products indicated classical pathway activation. Factor B conversion showed the alternative pathway to be involved as well. Total haemolytic complement activity was temporarily reduced, increasing without reaching normal values within 20 hours. The results indicated that the classical pathway was transiently activated, pointing to an acute antigen-antibody reaction, probably caused by the entrance of bacteria and bacterial products into the circulation of an immunized host.

Anaphylaxis↗
PubMed1983

Acute complement activation during an anaphylactoid reaction to blood transfusion and the disappearance rate of C3c and C3d from the circulation.

A patient experienced an anaphylactoid shock after receiving a transfusion with 5-10 ml of leucocyte-depleted blood. Complement measurements revealed pronounced elevation of split products of the third complement factor (C3c and C3d), normal but fluctuating levels of native C3, significantly decreased levels of C4, normal factor B concentrations and low levels of factor B split products. The results indicate complement activation via the classical pathway as a causative mechanism of the anaphylactoid shock, and suggest an antigen-antibody reaction as the etiological factor. The nature of the antigen-antibody reaction initiating the complement activation could not be established. The disappearance rate (T/2) of C3d from the plasma after the acute C-activation was measured to approximately 4 hr, and the half life of C3c was significantly shorter.

Adult↗