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Biomedical subjects

C M Arroyave

Publications and source records attributed to C M Arroyave.

At least 55 records · Page 3Linked to original sources
PubMed1977

Immune reactants in cryoproteins. Relationship to complement activation.

Cryoproteins were isolated from the serum of 5 patients with essential cryoglobulinaemia 5 patients with rheumatoid arthritis, and 2 patients with Sjøgren's syndrome. These cryoprecipitates contained IgG, IgM, and IgA as well as complement proteins C1q, C4, C3, and factor B. The cryoprecipitates were analysed further for content of antibody and antigen, and were tested for their ability to activate complement. In the cryoprecipitates of 2 patients with Sjøgren's syndrome, nuclear antigen and antinuclear antibody characteristic of an immunological specificity found in Sjøgren's syndrome were shown. The cryoprecipitates of 6 other patients contained rheumatoid factor and antibody to a lymphocyte nuclear antigen. The solubilized cryoprecipitates were tested by in vitro assays for their ability to activate complement by the classical or alternative pathways. All 12 cryoprecipitates activated the classical pathway. 9 of the 12 cryoprecipitates also activated the alternative complement pathway under conditions which did not involve activation of C1 and C4. These studies show that a high percentage of cryoprecipitates consist at least in part of immune reactants. We discuss the relationship of these findings to pathogenetic mechanisms in disease.

Aged↗
PubMed1977

Hypocomplementemia in chronic idiopathic urticaria.

A discrete evoking factor or presumed pathophysiologic mechanism is not recognized in the majority of patients with chronic urticaria or angioedema. Two cases are reported in which chronic urticaria was the main manifestation of an immune cutaneous vasculitis associated with hypocomplementemia attributable to classic and alternative mechanisms of complement activation. Among 72 consecutive patients evaluated for chronic urticaria, 10 additional patients with idiopathic urticaria were found to have hypocomplementemia. Of these, two had evidence of classic and alternative mechanisms of complement activation, five had evidence of only classic pathway activation, and three evidence of predominately or exclusively alternative pathway activation. Circulating immune complexes were found in the majority of patients with classic pathway activation. Hypocomplementemia may provide clues to pathophysiologic mechanisms operative in some patients with chronic urticaria.

Adult↗
PubMed1977

Mechanism of complement activation by radiographic contrast media.

Activation of the complement system by radiographic contrast media (RCM) was demonstrated by in vitro haemolytic and immunological assays. Such activation was found to be a function of the RCM molar concentration. Iodipamide was the most active of five RCM tested. When RCM was incubated with normal human serum (NHS) in the presence of ethylene glycol-tetra-acetic acid and magnesium ions, conditions which block activation of the classical pathway but permit activation of the alternative pathway, haemolytically active C3, properdin and factor B were found to be decreased but haemolytically active C4 was normal. Using counterimmunoelectrophoresis, the activation of complement was further demonstrated by detection of C3 and factor B-split products. Finally, when radiolabelled complement proteins were reacted with RCM in vitro and studied by density-gradient ultracentrifugation, it was demonstrated that a large complex was formed with a sedimentation of 22S, similar in characteristics to the C5b-C9 complex. It was postulated that the mechanisms of in vitro consumption of complement by RCM was mainly through the alternative pathway.

Complement C3↗
PubMed1977

Genetic deficiency of the fourth component of complement (C4) in Wistar rats.

A chance observation has led to the discovery of single component complement deficiency in Wistar rats. During serial total haemolytic activity (CH50) determinations on 10 male rats, 2 were consistently found to have values 20% or less than that of the others. An additional 30 males (200--220 g) and 20 females (180--200 g) were screened for CH50 and the defect was found in 10 of the males but none of the females. Mixtures of sera of high and low haemolytic activity gave intermediate values between the two populations arguing against the presence of an inhibitor of the complement system. Single component analysis revealed the defect to reside in the fourth component of complement (C4). Highly purified human C4 completely reconstituted the haemolytic activity of the complement deficient rat serum. A linear relationship between C4 and CH50 titres was observed. Data from preliminary selective breeding experiments point toward an autosomal recessive mode of inheritance. Animals with intermediate values were observed indicating a gene dosage effect with which the heterozygote may be recognized.

Animals↗
PubMed1976

Detection of complement activation by counterimmunoelectrophoresis (CIE).

Counterimmunoelectrophoresis (CIE) was used as a method of detecting activation of the third component of the complement system (C3). Highly purified C3, normal human serum (NHS), EDTA-treated plasma and serum activated with aggregated human immunoglobulin (agg-IgG) or inulin were used as sources of C3 and/or C3 split products. Activation of the alternative pathway of complement was assayed in the presence of EGTA (10 mM) and MgCl2 (0.3 mM), conditions which block activation of the classical pathway. When purified native C3, fresh NHS and fresh EDTA-plasma were tested in CIE against either antisera to whole C3 or to C3 split products, only one precipitin line was found, which was identified as native C3. However, when serum activated with agg-IgG or inulin were tested against the same reagents, two precipitin lines were seen. The first, with more cathodal mobility was identical to that of native C3. The second line had a more anodal mobility, was distinctly separated from the first and contained C3c and C3d as shown immunochemically with specific antisera. Native C3 and split products of C3 were identified by this CIE method in patients showing evidence of activated complement by having subnormal total complement (CH50) levels. When C3 split products were identified, the C3c-C3d precipitin line could always be distinguished from native C3 by its different electrophoretic mobility, even when C3 concentrations in serum varied from 0.25 mg/ml to 1.5 mg/ml. The sensitivity of CIE was compared to that of CH50 by asssaying at different time intervals after agg-IgG was added to fresh NHS. C3c-C3d split products were detected by CIE before any fall in CH50 and at all times when a significant decrease in CH50 was present. This study shows that the CIE technique is a highly sensitive, specific and rapid method for detecting activation of the complement system via classical or alternative pathways in human disease.

Complement C3↗
PubMed1976

Plasma histamine changes during provoked bronchospasm in asthmatic patients.

Seven patients with bronchial asthma underwent bronchial inhalation challenge with aerosolized allergen extracts and methacholine. Simultaneously, venous blood samples were collected and histamine was measured. Each patient was challenged on successive days with an allergen extract to which he had no skin-sensitizing antibody (skin test-negative allergen), followed by methacholine and skin test-positive allergen. Bronchospasm was not induced by inhalation of skin test-negative allergens but was observed in all patients after methacholine and in the majority of patients after skin test-positive allergens. No changes in plasma histamine were detected after challenges with methacholine and skin test-negative allergens. After challenge with skin test-positive allergens, significant rises in plasma histamine were detected in 5 of 7 patients. Plasma histamine was elevated within the first 5 min after inhalation of aerosolized allergen, and elevations persisted as long as 30 min. These studies showing that histamine increases significantly in the plasma during allergen-induced asthma in man suggest that histamine should be considered as at least one of the mediators of bronchospasm in allergic asthma. Bronchospasm induced by the cholinergic drug methacholine, unlike allergen-induced bronchospasm, is not associated with changes in plasma histamine.

Administration, Intranasal↗
PubMed1976

Oral aspirin challenges in asthmatic patients: a study of plasma histamine.

Under carefully controlled conditions, seven aspirin-intolerant asthmatic patients were challenged with oral aspirin and experienced respiratory tract reactions with a decline in forced expiratory volume in 1 sec (FEV1) ranging from 26 to 64%. Venous blood samples, which were collected during the challenges, showed a rise in plasma histamine in all seven patients. The increase in plasma histamine occurred at the onset of their respiratory reactions and those patients with the most severe asthmatic responses were found to have the highest and most prolonged levels of plasma histamine. The aspirin-intolerant asthmatic patients were able to ingest Maalox or sodium salicylate without untoward effects, decline in FEV1 values or changes in plasma histamine levels. Ten non-asthmatic individuals and eight out of ten asthmatic control patients were able to ingest aspirin without any reactions or changes in their plasma histamine levels. However, two asthmatic control individuals, with severe asthma requiring treatment with moderate dosages of corticosteroids, were found to have elevated pre-challenge plasma histamine levels which increased during their ASA challenges despite the absence of respiratory reactions or changes in FEV1 values. It is possible that these two individuals were unsuspected aspirin-intolerant asthmatics. These studies demonstrate that asthmatic reactions to acetylsalicylates are associated with release of histamine into plasma in the subgroup of asthmatic patients with the aspirin-intolerance syndrome. Such a finding suggests that histamine may be one of the mediators of bronchospasm in aspirin-induced asthma.

Administration, Oral↗
PubMed1976

Reaction to radiographic contrast agents: new developments in etiology.

Although a significant amount of histamine is released into plasma during contrast media injections, there still is no evidence to support an immunologic basis underlying contrast media reactions. This study supports previous observations that suggest in vitro leucocyte challenge may be of predictive value in contrast media reactions. Lassar's study in dogs and this study in humans clearly shows that complement activation by alternative pathway occurs during contrast agent administration. However, pathophysiological significance of this observation is not clear.

Adult↗
PubMed1976

Serum factors activating the alternative complement pathway in autoimmune disease: description of two different factors from patients with systemic lupus erythematosus.

Serum factors which activated the alternative pathway of complement were detected in 10 of 26 patients with systemic lupus erythematosus (SLE), three of 18 patients with mixed connective tissue disease, one patient with scleroderma, and one with Sjögren's syndrome. This activation was detected by conversion of factor B and C3 into split products and by lysis of glutathione-sensitized human erythrocytes under conditions where classical pathway activation was blocked. The serum factors capable of activating the alternative pathway could be seperated into 7S and 19S-type molecules by sucrose density gradient ultracentrifugation. In two patients with SLE, serum factors were isolated by ion-exchange chromatography, preparative electrophoresis, and molecular sieve chromatography. The serum 7S factor was immunochemically identical to the C3 nephritic factor (C3NeF) of hypocomplementemic chronic glomerulonephritis. Antisera to other complement components failed to react with this purified material. The 7S factor was able to activate the alternative pathway in C2 deficient serum, and in normal human serum under conditions where classical pathway was blocked, but was unable to do so in sera depleted of factor B, factor D, and C3. The activity could be removed by antiserum to C3NeF. In contrast, the serum 19S activator of the alternative pathway was not reactive with antiserum to C3NeF. It had a fast gamma mobility on electrophoresis and the activity could be removed by absorption with anti-IgG and anti-IgM. It was suggested that the 19S factors could consist, in part, of immune complexes.

Absorption↗
PubMed1976

Activation of the alternative complement pathway in systemic lupus erythematosus.

Serum factors activating the alternative pathway of complement in vitro, independent of classical pathway activation was demonstrated in six of eleven patients with systemic lupus erythematosus (SLE). These serum factors were detected by lysis of gluthathione-sensitized human erythrocytes and by C3 and factor B conversion in the presence of EGTA (10 mM) and MgCl2 (0-3 mM), conditions which blocked activation of the classical pathway but permitted activation of the alternative pathway. In order to determine if in vivo activation of the alternative pathway of complement was present in SLE, highly-purified factor B was labelled with radioactive iodine (125I), and its metabolism studied in the eleven patients with SLE and in twelve control subjects. All six patients with serum factors capable of activating the alternative pathway in vitro, had in vivo evidence of alternative pathway activation as measured by increased fractional catabolic rate (FCR) of factor B. Two patients without demonstrable alternative pathway activating factors in their sera had an elevated FCR of factor B. Six of the patients with increased FCR of factor B had disease limited to skin or joint and one had lupus nephritis which was inactive at the time of study. One of the four patients who were in clinical remission had elevated FCR. This study demonstrates that a significant number of patients with SLE of relatively mild disease activity had evidence of alternative complement pathway activation. This activation did not appear to be limited to patients with lupus nephritis and raises the possibility that it could also be related to some of the extra-renal manifestations of SLE.

Adolescent↗
PubMed1976

Activation of the alternative pathway of the complement system by radiographic contrast media.

Nine patients who underwent radiographic contrast media (RCM) infusion for diagnostic purposes were studied. Simultaneously, venous blood samples were collected and complement was measured. None of the patients had a clinical history of allergy to previous infusion of RCM. A significant drop in plasma complement (CH50) levels was detected in five of nine patients. The drop in CH50 was observed within the first 20 min after the initiation of RCM infusion. All five patients in whom a drop in complement was found showed a decrease in hemolytic C3, properdin, and factor B. In addition, by radial immunodiffusion low levels of C3, C6, properdin, and factor B were observed and split products of C3 and factor B were identified by immunoelectrophoresis. No significant changes in C1q and C4 were detected by radial immunodiffusion during the study of these five patients. This study strongly suggested that in some patients undergoing RCM infusion, activation of the complement system occurred and this activation appears to be through the alternative pathway.

Complement C1↗
PubMed1973

The membrane attack mechanism of complement. Reversible interactions among the five native components in free solution.

Reversible interactions in free solution were demonstrated to occur (a) between C5 and C8, (b) between C5, 6, 7 and C8, and (c) between C8 and C9. No interaction was observed between C8 and C6 or C7 and between C9 and C5, 6, 7. Interactions between C8 and C9 were enhanced at lowered ionic strength (0.05) and a molar excess of C8 over C9. Complex formation was independent of pH over the range of 6.5-8.5. Under optimal conditions the C8, 9 complex had a sedimentation coefficient of 10.2-10.6S, while native C8 and C9 sedimented at 8.5 and 4.8S, respectively. Specificity and reversibility of these interactions were established. In spite of the limited number of interactions observed, all five of the native proteins of the membrane attack mechanism interacted to form an association product that sedimented at 10.8-11.2S. Demonstration of this product in free solution supports the concept that C5-9 on acquisition of cytolytic activity assemble into a stable multimolecular complex.

Animals↗
PubMed1972

Molecular analysis of the membrane attack mechanism of complement.

The molecular arrangement of the membrane attack mechanism of complement was explored. The molar ratios of the components within the C5-9 assembly on the target cell surface were determined using human complement proteins in highly purified and radiolabeled form. With the aid of monospecific complement antisera it was possible to probe the spatial relationships between the components of the assembly. C5 and C6, in the presence of C7, were bound to EAC1-3 in equimolar quantities irrespective of the amounts and the relative proportions of C5, C6, and C7 offered. The amount of C8 bound to EAC1-7 increased with input and at saturation of all C8 binding sites the molar ratio of bound C8/bound C5 approached 1.0. Uptake of C9 by EAC1-8 increased with input and at saturation of all C9 binding sites the molar ratio of bound C9/bound C8 became 6.0. However, calculations suggest that the binding of three C9 molecules to one C8 molecule is sufficient to achieve a full hemolytic effect. Evidence was obtained indicating that binding and hemolytic function of C9 depends upon cooperative interaction of multiple C9 molecules. Binding of C8 to EAC1-7 and the generation of hemolytic C8 sites were inhibited by antibody to either C5, C6, or C7. Uptake of C9 by EAC1-8 and the generation of hemolytic C9 sites were strongly inhibited by anti-C8 and to a lesser degree by anti-C5. Binding of C9 (but not hemolysis) was also reduced by antibody to C6 or C7. The data are consistent with the concept that the fully assembled membrane attack mechanism of complement consists of a decamolecular complex: a trimolecular arrangement composed of C5, C6, and C7 forms the binding site for one C8 molecule which in turn furnishes binding sites for six C9 molecules, saturation of three sites apparently being sufficient for expression of full cytolytic activity of the complex. This work made it possible to design a simple molecular model.

Animals↗
PubMedDate not supplied

Cobra venom factor, an activator of the complement system, enhances the bowel necrosis induced by platelet-activating factor.

We have previously produced an experimental model of ischemic bowel necrosis in the rat by injecting platelet activating factor (PAF) (7 micrograms/kg) into the mesenteric vascular bed. The dose of PAF required to produce necrosis could be reduced to 50% if the animal was pretreated with bacterial endotoxin (lipopolysaccharide) (20 micrograms/rat). The mechanism of this potentiating effect of lipopolysaccharide is unclear, but activation of the complement system may be one of the contributing factors. To investigate the role of the complement system, we injected cobra venom factor (CVF) (1 unit/kg) to activate the complement system before injection of PAF (2 micrograms/kg) into the superior mesenteric artery. CVF and PAF were also injected separately at the same dosage to other groups of rats. CVF activated the complement system, but by itself did not produce gross necrosis of the bowel. PAF alone caused 3 out of 9 rats treated to develop bowel necrosis. In contrast, combination of the two produced bowel necrosis in all 6 rats thus treated. CVF did not enhance the effects of PAF on hemoconcentration and leukopenia, but aggravated the hypotension caused by PAF. PAF, on the other hand, also enhanced activation of the complement system by CVF. To investigate the specificity of PAF on complement activation, lyso-PAF was used in combination with CVF. It was found that lyso-PAF did not have a significant potentiating effect on CVF-induced complement activation and, by itself, it had no effect on complement activation, blood pressure, white blood cell count or hematocrit. Lyso-PAF, with or without CVF, also failed to produce bowel necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

An in vitro assay for radiographic contrast media idiosyncrasy.

Adverse reactions related to the use of iodine-containing radiographic contrast media (RCM) continue to present a significant problem in diagnostic radiology. This study was designed to test an in vitro assay that can probably be used before infusion of RCM to predict patients with high risk of developing contrast media reactions. Peripheral leukocytes of 23 patients with a positive history of RCM incompatibility or idiosyncrasy, 89 atopic individuals, and 49 normal, nonatopic volunteers were stimulated in vitro with three RCM in different concentrations, and the amount of histamine released was measured in the supernatant. There was a significant increase in histamine release induced by RCM in the majority of patients with RCM idiosyncrasy, and in patients with atopic disease. Normal leukocytes, when incubated with serum from high-releasing or atopic patients, did not show increased histamine release after stimulation with the respective RCM. The increased releasability of patients' leukocytes could not be transferred by serum. Our results show that leukocytes' histamine release is higher in patients with a positive history of RCM incompatibility and patients with atopic disease. This in vitro assay might be a useful diagnostic tool for detecting patients with a high risk of developing contrast media reactions.

Contrast Media↗