The relationship of plasma histamine to the activity of bronchial asthma.
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Adolescent↗
Biomedical subjects
E M Tan
Publications and source records attributed to E M Tan.
Mixed connective tissue disease in childhood. A clinical and serologic survey.
Mixed connective tissue disease is a syndrome with overlapping clinical features of SLE, scleroderma, and polymyositis. Only one other child with MCTD has been described in detail. In this study 14 children with MCTD are described. Each had overlapping clinical findings that evolved over an extended period of observation, and all 14 had high serum titers of speckled ANA and antibodies to RNP. A serologic survey of 127 children with various rheumatic diseases confirmed the specificity of high titer of speckled ANA and antibodies to RNP for MCTD in children. Significant cardiac and renal involvement, and thrombocytopenia, may be more common in affected children than in adults with MCTD, may lead to longer therapy with higher doses of a corticosteroid, and may contribute to a more serious prognosis than in adults.
Adolescent↗
Plasma complement changes during bronchospasm provoked in asthmatic patients.
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Aerosols↗
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↗
Histopathological changes in mice treated with extracts of the histamine-sensitizing factor of Bordetella pertussis.
The histamine-sensitizing factor (HSF) of Bordetella pertussis was isolated in a highly purified form. In addition to inducing profound sensitization to histamine, it also caused a significant lymphocytosis and produced an enhancement of reaginic antibody production in animals upon immunization with antigen. Biologically active doses of HSF produced significant pathological changes in mice including congestion and edema of the lung and a marked depletion of cells in the thymus, white pulp of the spleen, and lymph nodes. The lymphocytosis and histological changes in the lungs and lymphoid organs were observed in different strains of mice injected with HSF (even those that are resistant to its histamine-sensitizing effects). Heating HSF at 80 degrees C for 30 min, a treatment that destroys histamine sensitizing and lymphocytosis promoting activities, completely abolishes the ability to induce the changes observed in the lungs and lymphoid organs.
Adjuvants, Immunologic↗
Mixed connective tissue disease in children.
Seven girls and 3 boys with MCTD have been described. As a group their clinical characteristics and serological findings are similar to those reported in adults, with several important differences. Children with MCTD may have marked thrombocytopenia and more frequently they have RF. Significant cardiac and renal involvement are more common in children, may lead to longer and higher dose corticosteroid therapy, and may contribute to a less optimistic prognosis than that described in adults.
Adolescent↗
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↗
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↗
Hypersensitivity to histamine and systemic anaphylaxis in mice with pharmacologic beta adrenergic blockade: protection by nucleotides.
The effects of exogenous nucleotides on the histamine hypersensitivity of pharmacologically beta-blocked mice were investigated. Female HLA-SW (ICR) mice, 27-29 gm, were injected intraperitoneally with 20 to 100 mug of propranolol 45 min before intraperitoneal challenge with 1 mg histamine. These animals had a mortality which averaged approximately 80%. At various time intervals before histamine, doses of from 0.5 to 12 mumoles of nucleotides were administered intravenously. Noncyclic nucleotides, adenosine, adenosine 5'-monophosphate (AMP), and guanosine 5'-monophosphate (GMP) showed clear, dose-response protection against histamine death of propranolol-treated mice when they were given 45 to 90 min before histamine. Cyclic AMP showed significant protection only when it was given at a dose of 8 mumoles 45 to 90 min before histamine, and lower or higher doses gave equivocal or no protection. Cyclic GMP WAS Not protective at any dose tested. Propranolol treatment also produced enhanced sensitivity to passive systemic anaphylaxis. Mice were passively sensitized by intraperitoneal injection of mouse anti-egg albumin antibody 6 hr before intravenous challenge with 0.5 mg egg albumin. The mortality from anaphylaxis in the group treated with 20 mug propranolol 45 min before antigen challenge increased to 83%, while that of the group not given propranolol was only 10%. Nucleotides were given intravenously 45 min before antigen challenge. The nucleotides that protected mice from death due to histamine challenge also protected them from death due to systemic anaphylaxis. These protective nucleotides were the same nucleotides that had been reported previously to be protective against Bordetella pertussis-induced hypersensitivity to histamine and anaphylaxis.
Adenosine↗
Histamine hypersensitivity in mice induced by Bordetella pertussis or pharmacologic beta adrenergic blockade. Effects of adrenergic, cholinergic, and other drugs.
The effects of prostaglandin E1, E2, F2alpha (PGE2 PGF2alpha), isoproterenol, epinephrine, norepinephrine, salbutamol, practolol, atropine, aminophylline, and corticosterone on the hypersensitivity to anaphylaxis, histamine, and serotonin in Bordetella pertussis-treated mice and propranolol-treated mice were investigated. Female HLA-SW (ICR) mice, 27-29 gm, were injected with pertussis vaccine intravenously 4 days before challenge with antigen, histamine, or serotonin. Alternatively, instead of pertussis vaccine, propranolol was injected intraperitoneally 45 min before histamine challenge. Test drugs were administered intraperitoneally 15 min before challenge. PGE1 and PGE2 at a narrow range of between 10 and 100 mug and epinephrine at 100 mug protected both pertussis- and propranolol-treated mice. Isoproterenol (25 mug) and aminophilline (800 mug) protected beta-blocked mice, but did not protect pertussis-treated mice even with very high doses (1,000 and 3,2000 mug, respectively), although salbutamol (500 mug) did. PGF2alpha, norepinephrine, and atropine were not protective at all. Practolol, a beta 1-blocker, given intraperitoneally 30 min before histamine neither sensitized normal mice nor changed the effect of isoproterenol or salbutamol in pertussis-treated mice. Corticosterone 10 mg/kg reduced the number of deaths from histamine in beta-blocked mice, but not in pertussis-treated mice. The protective effect is discussed in connection with probable effects of the drugs on intracellular cyclic adenosine monophosphate (cAMP) levels.
Adrenergic beta-Antagonists↗
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↗
Immunopathology and pathogenesis of cutaneous involvement in systemic lupus erythematosus.
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Animals↗
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↗
Studies on antibodies to histones by immunofluorescence.
When mouse kidney tissue sections were extracted with 0.1 N hydrochloric acid, sera with antibodies to certain nuclear antigens no longer stained tissue nuclei by immunofluorescence. This effect was due to removal of histones and nuclear acidic proteins Sm and nuclear ribonucleoprotein by the acid. DNA remained in the nuclei of the acid-extracted tissue sections. When solutions of calf thymus histones were reacted with acid-extracted tissues, histones combined with nuclear DNA to form complexes of DNA-histone. These complexes contained antigenic determinants which reacted with sera containing antibodies to deoxyribonucleoprotein to give nuclear staining demonstrated by immunofluorescence. The reaction was immunologically specific in that sera with antibodies to Sm and nuclear ribonucleoprotein were not reactive with reconstituted DNA-histone in nuclei. Other basic proteins such as protamine, poly-L-lysine, and poly-L-arginine could not substitute for histones. The method is introduced as a specific and reproducible assay for study of antibodies to histones.
Antibodies, Antinuclear↗
Enhancement of reaginic and hemagglutinating antibody production by an extract of Bordetella pertussis containing histamine sensitizing factor.
The effect of an extract containing the histamine-sensitizing factor (HSF) of Bordetella pertussis on the immune response of mice to ovalbumin was investigated with respect to dose of antigen and adjuvant. Of particular interest was the enhancement of reaginic antibody production. In comparison to the Al(OH)3 induced production of reaginic antibody where low doses of antigen and adjuvant yield high titers of reagin, the HSF extract demonstrated optimal adjuvant activity at high doses of both adjuvant and antigen. The reaginic antibody response was maximal usually by 2 to 3 weeks post-immunization and persisted for long periods of time. The hemagglutinating antibody response was maximal at 8 to 10 weeks post-immunization. The initial treatment of mice with HSF extract plus antigen resulted in the production of memory cells since a subsequent immunization with ovalbumin alone evoked a secondary reaginic response. These observations may have implications in clinical allergy since substances similar to the pertussis factor might be produced by other microbial organisms and these substances could modulate the immunologic response of individuals to common allergens.
Adjuvants, Immunologic↗
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↗
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↗
Transtracheal aspiration studies in asthmatic patients in relapse with "infective" asthma and in subjects without respiratory disease.
Exacerbations of bronchial asthma that cannot be accounted for by allergic reactions have sometimes been called "infective" asthma. The validity of this designation was tested by study of transtracheal aspirates (TTA) obtained from 27 asthmatic patients in relapse who had findings suggestive of respiratory infection and 12 subjects without respiratory disease. Aspirates were cultured for aerobic and anaerobic bacteria, Mycobacteria, fungi, Mycoplasma, and viruses. A comparable variety of bacterial and fungal growth in small numbers was obtained from a majority of both groups. Microbial growth did not correlate with the presence of symptoms or signs compatible with infection. Aspirates from asthmatics with chronic bronchitis, immediate hypersensitivity to aeroallergens, or aspirin intolerance yielded no greater growth than did aspirates from asthmatics without these characteristics. In only one asthmatic was there suggestion that overt infection of the lower respiratory tract contributed to exacerbation of asthma. These results do not lend support to the empiric use of antibiotics in the management of unexplained asthmatic relapse.
Adolescent↗