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Biomedical subjects

O Cromwell

Publications and source records attributed to O Cromwell.

89 records · Page 5Linked to original sources
PubMed1984

Preferential generation of leukotriene C4 by human eosinophils.

The leukotriene generating capacities of ionophore stimulated human eosinophils and neutrophils were compared using specific radioimmunoassays for LTB4 and LTC4. Mixed granulocyte preparations (neutrophils and eosinophils) produced both LTB4 and LTC4 in a time-dependent fashion which was maximal at 10 and 15 min, respectively. Following the separation of eosinophils (greater than 75%) and neutrophils (greater than 90%) by metrizamide gradients, LTC4 production was predominantly from eosinophils, whereas neutrophils were the principal source of LTB4. The concentrations of leukotrienes produced by the eosinophil and neutrophil rich cell preparations were directly proportional to the concentration of ionophore. Following purification of eosinophil derived products by RP-HPLC the LTC4 immunoreactivity corresponded to the elution profile of a synthetic LTC4 marker. Furthermore, in 32 atopic subjects (21 bronchial asthmatics and 11 non-asthmatics) the amounts of LTC4 produced by unseparated leucocytes were directly proportional to the percentage of eosinophils in the total cell suspension. Preferential generation of LTB4 by neutrophils was also demonstrated by immunoreactivity of ionophore stimulated supernatants subjected to RP-HPLC, as well as by its characteristic u.v. absorbance and GC-MS profile and the ability to promote directional neutrophil locomotion (chemotaxis). These experiments support the concept that eosinophils accumulate in tissues partly as a result of the response to neutrophil derived LTB4, and that these cells contribute to the production of sulphidopeptide leukotrienes with subsequent amplification of the acute allergic response.

Adolescent↗
PubMed1984

Sputum leukotrienes in obstructive airways diseases.

Sputum samples from patients with bronchial asthma, chronic bronchitis and cystic fibrosis were examined for the presence of leukotrienes B4, C4 and D4. Following ethanol extraction and purification on Amberlite XAD-8, leukotrienes were identified by high pressure liquid chromatography (HPLC) using the appropriate markers. Fractions from HLPC were also tested for biological activity using both the Boyden chemotaxis assay and FPL 55712 inhibitable contraction of the isolated guinea-pig ileum. LTB4 was detected in the HPLC fractionated sputa from bronchial asthma (seven of seven), chronic bronchitis (four of four) and cystic fibrosis (four of four). In contrast, bioassay on the guinea-pig ileum failed to detect LTC4 or LTD4 in 17 asthmatic sputa, although they were detected in one of five bronchitics and 16 of 25 patients with cystic fibrosis. The activity in eight of these cystic fibrosis sputa was further characterized by HPLC and shown to be LTC4 and/or LTD4. Sputum from 11 of 17 asthmatics, four of 25 patients with cystic fibrosis and two of five bronchitics contained an anaphylatoxin like substance. The majority of sputum samples containing LTB4 also possessed an activity with physical and biological characteristics of the 5(S), 12(S), 6-trans LTB4 isomer. These studies indicate that lipoxygenase products of arachidonic acid metabolism are present in the sputum in various forms of obstructive airways disease. The failure to detect the 'SRS-A' leukotrienes in sputum from bronchial asthma may be attributable to either losses during extraction, the insensitivity of the assay procedure or to more rapid catabolism of LTC4 and LTD4 by bronchial secretions in asthma than in cystic fibrosis.

Asthma↗
PubMed1983

Neutrophil chemotactic activity in milk-induced asthma.

Four subjects with clinical histories of milk-induced asthma were studied (three allergic to cow's milk; one to soya milk). In each instance, skin prick tests, RAST (IgE and IgG4), the basophil histamine release, and serum precipitins, using appropriate milk extracts, were negative. After the ingestion of milk all the subjects developed a reproducible and dose-dependent increase in airflow limitation. Three patients (two allergic to cow's milk; one to soya milk) gave a characteristic immediate-type reaction, which was maximal at 30 min after challenge. The fourth individual developed an isolated late-phase response, with maximal airways obstruction 3 hr after ingesting milk. In the three subjects who gave an early reaction, wheezing was accompanied by an elevation in circulating neutrophil chemotactic activity (NCA). This was not observed in the individual with the isolated late reaction. By Sephacryl S-400 gel-filtration chromatography it was shown that NCA of the early reactions eluted with proteins having an estimated molecular weight of 600,000 daltons. The immediate asthmatic response in peak expiratory flow rate and the elevation in NCA were inhibited by the prior oral administration of either disodium cromoglycate (DSCG) or oral beclomethasone dipropionate (BDP). In contrast, DSCG had no effect on airways obstruction in the subject with the isolated late asthmatic response, although inhibition was achieved by BDP.

Adult↗
PubMed1983

Immunologic release of neutrophil chemotactic activity from human lung tissue.

The release of heat-stable neutrophil chemotactic activity (NCA) has been detected after challenge of isolated human lung tissue with anti-IgE. The major NCA released (NCAL) had similar physicochemical properties to the NCA detected in the circulation of asthmatic subjects after bronchial challenge with specific antigen (NCAAG). NCAL and NCAAG (1) had molecular weights of approximately 600,000 daltons as estimated by Sephacryl S-300 gel-filtration chromatography; (2) both eluted from DEAE-Sephacel (pH 7.8) between 0.1 and 0.2 molar NaCl; (3) had isoelectric points of between 6.5 and 6.8 as determined by chromatofocusing on Polybuffer Exchanger 94. In contrast to NCAAG, lung-derived neutrophil chemotactic activity appeared to be more heterogeneous after gel-filtration and anion-exchange chromatography. The release of NCA was complete by 15 min and there was no evidence of further release up to 12 hr. These observations indicate that high-molecular-weight NCA released from human lung tissue has similar properties to NCAAG and would support the view that NCAAG originates from lung tissue after antigen bronchial challenge in asthmatic subjects.

Chemotactic Factors↗
PubMed1982

Identification of leukotrienes in the sputum of patients with cystic fibrosis.

Sputum extracts from 16 of 25 adult patients with CF produced a slow, sustained contraction of isolated guinea pig ileum which was partially inhibitable by the SRS-A antagonist FPL 55712. Following progressive purification and HPLC, the major ileum-contracting substance was identified as LTD4. LTC4 was also present but in smaller amounts. The sputum contained other SRS-A-like activity which was not inhibited by FPL 55712; this substance was of a smaller molecular size than LTD4. The presence of LTB4 was also established using HPLC and an assay of neutrophil chemotaxis. These studies raise the possibility that leukotrienes and other lipoxygenase products may contribute to the progressive lung disease characteristics of CF.

Adolescent↗
PubMed1981

Toluene-diisocyanate induced asthma: evaluation of antibodies in the serum of affected workers against a tolyl mono-isocyanate protein conjugate.

Radioallergosorbent testing was used to look for the presence of specific IgE antibody against a para-tolyl-mono-isocyanate human serum albumin conjugate in sera from five groups of subjects. The first three groups consisted of individuals exposed to toluene diisocyanate (TDI) who had been shown by bronchial provocation testing with levels of TDI below the threshold limit value of 0.02 parts/10(6), to have immediate asthmatic reactions, late asthmatic reactions or no respiratory changes at all. The two control groups consisted of atopic and non-atopic individuals who had no respiratory symptoms and no known exposure to TDI. Although RAST showed high ct/min in some of the sera from patients with proven TDI-induced respiratory disease, these levels were not significantly different from controls and appeared to reflect the presence in these sera of high levels of total IgE (greater than 100 mu ml--1). There is no evidence from this study for the presence of specific IgE antibody against a para-tolyl mono isocyanate human serum albumin conjugate in patients with TDI-induced respiratory disease. This finding may reflect absence of antibodies, or that the techniques for their detection are not always effective even when performed by experienced persons, and there is a potential source of error in the interpretation of results when sera contain large amounts of IgE.

Antibody Formation↗
PubMed1981

Evidence of increased histamine levels of lung lavage fluids from patients with cryptogenic fibrosing alveolitis.

In this study we report a significant increase in histamine in lung lavage fluids from a group of 33 patients with lone cryptogenic fibrosing alveolitis (lone CFA), and from a group of 13 patients having CFA in association with other connective tissue disorders, when compared with findings for 13 smoking patient controls without peripheral lung disease (P less than 0.001, P less than 0.05 respectively). The increases were independent of smoking or treatment. Significant correlations were obtained between the raised histamine levels in CFA and increased levels of albumin and increased counts of neutrophils and eosinophils in the lavage fluids, and with more pronounced fibrosis in CFA lung biopsies.. Thus histamine is associated with features of inflammation relating to progressive or more severe disease. No significant increase in histamine was observed in a group of 22 patients with sarcoidosis, although 21 had evidence of disease involving the lung parenchyma. There were, however, significantly higher levels in the patients with X-ray evidence of upper lobe contraction, suggestive of "fibrosis" (P less than 0.025). The levels also showed a correlation with increasing counts of lavage neutrophils (P less than 0.005), a feature also associated with X-ray evidence of contraction in this group. Mast cells were readily identified in biopsies from 12 CFA patients suggesting that these cells may provide one possible source of histamine in CFA lungs. These observations raise the question whether histamine, and/or possibly other substances derived from mast cells, plays any role in amplifying inflammation associated with pulmonary fibrosis.

Adult↗
PubMed1980

Histamine release from blood of asthmatics.

A group of forty-two steroid-dependent perennial asthmatics was studied over a 13-week period incuding the 8 weeks of a double-blind controlled trial of oral sodium cromoglycate. Given at a dose of 200 mg four times per day the drug provided no significant benefit to the patients when compared with results for those on placebo. Blood from eleven patients consistently failed to release more than 25% of the total cellular histamine when challenged with a range of concentrations of antibody to IgE. All six of the cryptogenic (intrinsic) asthmatics in the trial fell within this group, together with 2/12 asthmatics with negative skin tests but suggestive clinical histories implicating common alergens, and 3/24 extrinsic asthmastics with positive skin prick tests. There was no correlation between drug usage and histamine release in response to challenge with antibody to IgE.

Adult↗
PubMed1979

Passive transfer in man and the monkey of Type I allergy due to heat labile and heat stable antibody to complex salts of platinum.

Passive transfer (P-K) tests have been performed in man and monkeys with sera from a group of six refinery workers sensitive to ammonium hexachloroplatinate and tetrachloroplatinite. Positive (P-K) prick test reactions were elicited in three human recipients and in the monkey to three of the test sera. The other three sera gave inconsistent results in man and negative results in monkeys and these differences appeared to correspond with the duration of exposure of the workers. The passive transfer tests did not correlate with the intensity of the prick test reactions in the donors or with the RAST; there was partial correlation with total levels of IgE. Antigen mediated histamine release from whole blood and washed leucocytes from two of the six subjects correlated with the RAST and P-K levels. These findings confirm the presence of specific IgE antibody to the platinum salts, and also of heat stable, short-term sensitising antibodies, presumably STS-IgG.

Adult↗
PubMed1979

Specific IgE antibodies to platinum salts in sensitized workers.

A RAST has been developed for the measurement of IgE antibodies specific to platinum chloride complexes in sensitized workers. Human serum albumin covalently linked to Sepharose beads by the cyanogen bromide method was reacted with ammonium tetrachloroplatinite (II) (NH4)2PtCl4. This conjugate was more suitable for the RAST, than conjugates of HSA and the platinum salt prepared in solution and then linked to the activated Sepharose, showing better sensitivity and giving lower levels of non-specific uptake of IgE from sera of non-exposed subjects with high total levels of IgE, e.g. allergic bronchopulmonary aspergillotics.

Antibody Specificity↗
PubMed1979

Blood histamine levels after exercise testing.

Histamine has been measured in whole blood and in the plasma of twenty-three subjects following exercise testing of seventeen asthmatics and six normal controls. Whole blood histamine rose in both asthmatics and controls and was associated with a concomitant rise in the basophil count. Plasma histamine in the peripheral venous blood only rose in one patient who developed urticaria after exercise.

Asthma↗
PubMedDate not supplied

Activated human eosinophils generate SRS-A leukotrienes following IgG-dependent stimulation.

Eosinophils, a class of granular leukocytes, are prominent in many inflammatory processes, particularly in asthma, certain allergic diseases and during infections with helminthic parasites. Following incubation with the Ca ionophore A23187 (refs 1-4) (a non-physiological agent which circumvents membrane calcium-gating mechanisms), eosinophils generate large amounts of sulphidopeptide leukotrienes, potent inducers of smooth muscle constriction and mucus production. These are now known to represent the activity previously termed 'slow-reacting substance of anaphylaxis' (SRS-A) but attempts to identify a physiological stimulus for SRS-A production by eosinophils have so far been unsuccessful. The cells contain recognized receptors for IgG (Fc) and it is known that they adhere to, and can be activated by, contact with the surface of large organisms such as helminthic larvae. We show here that eosinophils, particularly when activated, produce sulphidopeptide leukotrienes after contact with large particles coated with IgG.

Eosinophilia↗
PubMedDate not supplied

Sensitization to different mite species in German farmers: clinical aspects.

Various mite species referred to collectively as house dust and storage mites are recognized worldwide as a cause of allergic airway disease. Our study aimed to investigate the frequency of sensitization and potential importance of mite species in farmers using a broad mite spectrum. A total of 86 German farmers with rhinitis and/or asthma were studied by skin prick testing and/or enzyme allergosorbent test (EAST) with the following mites: Blomia tjibodas, Blomia tropicalis, Blomia kulagini, Glycyphagus domesticus, Thyreophagus entomophagus, Euroglyphus maynei, Chortoglyphus arcuatus, Dermatophagoides pteronyssinus, Dermatophagoides farinae, Acarus siro, Lepidoglyphus destructor, Tyrophagus putrescentiae, Acarus farris and Cheyletus eruditus. Sensitization to at least one mite species was detected in 51 patients (59%) by skin prick testing, and in 31 patients (36%) by EAST. The most frequent sensitizations determined by skin tests were found for the three Blomia species, E. maynei and G. domesticus. Twelve patients (14%) gave a positive EAST with the predator mite C. eruditus. A total of 22 patients gave positive EAST results with the Dermatophagoides species. We were able to document sensitization to C. arcuatus, E. maynei and T. entomophagus for the first time in Germany. A considerable proportion of the German farmers tested were sensitized to storage mites. The allergological potential of various mite species has been recognized, some for the first time. It was concluded that B. tjibodas, G. domesticus, C. arcuatus and C. eruditus in particular should be included in an allergy diagnosis. Further investigations into the clinical relevance of the sensitizations and possible cross-reactivity between the mite species are necessary.

Adult↗