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Biomedical subjects

S Poole

Publications and source records attributed to S Poole.

At least 127 records · Page 7Linked to original sources
PubMed1991

The international standards for interleukin-1 alpha and interleukin-1 beta. Evaluation in an international collaborative study.

Three ampouled preparations of interleukin-1 alpha (IL-1 alpha) and three ampouled preparations of interleukin-1 beta (IL-1 beta) were evaluated by 13 laboratories in six countries for their suitability to serve as international standards for these materials. The preparation were assayed in in vitro and in vivo bioassays, radioreceptor assays and immunoassays. On the basis of the results reported here, with the agreement of participants in the study and with the authorization of the Expert Committee on Biological Standardization (ECBS) of the World Health Organization (WHO), one of the preparations of IL-1 alpha and one of the preparations of IL-1 beta were established as international standards for these materials. Further, since the relative activities of IL-1 alpha and IL-1 beta were dependent upon the assay systems used, it was decided that reference should be made to units of IL-1 alpha activity or IL-1 beta activity rather than to IL-1 activity.

Evaluation Studies as Topic↗
PubMed1991

Variability in LPS composition, antigenicity and reactogenicity of phase variants of Bordetella pertussis.

Comparison of lipopolysaccharides (LPS) from phase variants of different strains of Bordetella phase variants of different strains of Bordetella pertussis has shown a difference in their composition, antigenicity and reactogenicity. Phase I variants of B. pertussis, with the exception of strain 134, contain a preponderance of LPS I whereas the major component of LPS of phase IV variants is LPS II. Sera raised to LPSs of phase I strains, other than 134, cross-react with each other but not with phase IV LPSs; and similarly all sera raised to phase IV LPSs cross-react with each other and with LPS from 134 phase I. The LPSs of all phase I variants, including that of 134, are approximately ten-fold or more reactive in the limulus amoebocyte lysate assay (LAL) than phase IV LPSs. In the human mononuclear cell pyrogen assay phase IV LPSs also stimulated a lower response than phase I LPSs. The B. pertussis phase I LPSs are 10-times more reactive than Escherichia coli standard endotoxin in the LAL assay but 100-times less reactive than E. coli LPS in the monocyte test for pyrogen. The SDS-PAGE profiles of B. pertussis LPSs are quite different from those of B. parapertussis and B. bronchiseptica strains. B. pertussis LPSs produced a typical lipo-oligosaccharide (LOS) pattern. B. bronchiseptica LPS produced a similar pattern but was antigenically distinct from B. pertussis LPSs I and II. B. parapertussis in contrast produced a ladder pattern typical of smooth type LPS.

Animals↗
PubMed1991

Interleukin-8 as a mediator of sympathetic pain.

1. The hyperalgesic effects of interleukin-8 (IL-8), interleukin-1 beta (IL-1 beta) and carrageenin were measured in a rat paw pressure test. 2. IL-8 evoked a dose-dependent hyperalgesia which was attenuated by a specific antiserum, the beta-adrenoceptor antagonists atenolol and propranolol, the dopamine receptor antagonist SCH 23390 and the adrenergic neurone-blocking agent guanethidine. The hyperalgesia was not attenuated by the cyclooxygenase inhibitor indomethacin or the IL-1 beta analogue Lys-D-Pro-Thr. 3. IL-1 beta-evoked hyperalgesia was attenuated by indomethacin and Lys-D-Pro-Thr but not by atenolol or SCH 23390. 4. Carrageenin-evoked hyperalgesia was attenuated by atenolol, indomethacin and anti-IL-8 serum. The effects of atenolol and anti-IL-8 serum were not additive. The effects of indomethacin and anti-IL-8 serum were additive: this combination abolished carrageenin-evoked hyperalgesia. 5. A new biological activity of IL-8 is described, namely the capacity to evoke hyperalgesia by a prostaglandin-independent mechanism. IL-8 is the first endogenous mediator to be identified as evoking hyperalgesia involving the sympathetic nervous system. Since IL-8 is released by activated macrophages and endothelial cells it may be a humoral link between tissue injury and sympathetic hyperalgesia.

Animals↗
PubMed1991

Assay of pyrogens by interleukin-6 release from monocytic cell lines.

A novel in-vitro system has been developed for the detection and quantification of pyrogen in pharmaceutical products. The measured variable was evoked secretion of the pyrogenic cytokine interleukin-6 from MONO MAC 6 monocytic cells incubated with the product. The interleukin-6 was detected using a specific and sensitive ELISA developed for this purpose. The test system detected pyrogenic contamination in 3 batches of therapeutic human serum albumin which had caused adverse reactions in recipients. The contamination was not detected in conventional tests: the rabbit pyrogen test and the limulus amoebocyte lysate test.

Animals↗
PubMed1991

Interleukin-1 beta production in vivo and in vitro in rats and mice measured using specific immunoradiometric assays.

Activated cells of the monocyte-macrophage lineage produce two forms of the inflammatory cytokine interleukin-1 (IL-1), IL-1 alpha and IL-1 beta, of which IL-1 beta is the predominant secreted form and has a wide range of modulatory effects on the endocrine system. Immunoassays of human IL-1 beta have been described, but are not suitable for measurement of rat and mouse IL-1 beta because of limited cross-reactivity. Polyclonal sheep anti-rat or sheep anti-mouse IL-1 beta antisera were used to develop sensitive and specific immunoradiometric assays for rat and mouse IL-1 beta. Secretion of IL-1 beta from endotoxin-activated monocytes or macrophages was measured in vitro or in vivo in both species. In vitro, rat monocytes and mouse macrophages produced IL-1 beta in response to endotoxin, with a relatively small proportion of total IL-1 beta being secreted. In vivo, endotoxin stimulated an increase in plasma IL-1 beta in both animals. The development of these assays will facilitate studies of the role of endogenous IL-1 beta in animal endocrine models.

Animals↗
PubMed1990

Absence of correlations between indices of systemic inflammation and synovial fluid interleukin 1 (alpha and beta) in rheumatic diseases.

There are two forms of the cytokine interleukin 1 (IL1), produced by two distinct genes encoding a neutral (IL1 beta) and an acidic (IL1 alpha) peptide. They have powerful pro-inflammatory, immunopotentiating, catabolic and arthritogenic properties in vivo and have been implicated in the pathogenesis of rheumatic diseases. In this study, using specific immunoassays, we have measured both IL1 alpha and IL1 beta levels in synovial fluids (SF) from a large number of patients with different rheumatic diseases. Biologically significant levels of both cytokines were found in SF from patients with different forms of arthritis, but no correlations were found with any of the measures of disease activity that we tested. We also describe the presence in joint exudates of biological inhibitor(s) that neutralize IL1-induced T-cell activation. This is the first report of IL1 alpha and IL1 beta measurements in the same synovial exudates and also of the comparison of local levels of these cytokines with conventional indices of systemic inflammation.

Arthritis↗
PubMed1990

Recombinant interleukin-1 and tumor necrosis factor induce neutrophil migration "in vivo" by indirect mechanisms.

The alpha and beta forms of recombinant interleukin-1 (IL-1 alpha and IL-1 beta) and of recombinant Tumor Necrosis Factor (TNF alpha and TNF beta) induced dose-dependent neutrophil migration into rat peritoneal cavities. Migration induced by both IL-1s showed a bell-shaped dose-response curve and IL-1 beta was 3-fold more potent than IL-1 alpha. Pretreatment of the animals with dexamethasone or depletion of the peritoneal macrophage population, abolished the neutrophil migration induced by the four cytokines. "In vitro" stimulation of macrophage monolayers with IL-1 beta and the TNFs released a factor into the supernatant which, unlike these cytokines, induced neutrophil migration in dexamethasone pretreated animals. These results suggest that the neutrophil migration induced by IL-1 alpha, IL-1 beta, TNF alpha and TNF beta is not due to a direct effect on neutrophils, but occurs via the release of a chemotactic factor(s) from resident macrophages.

Animals↗
PubMed1990

Fate of injected interleukin 1 in rats: sequestration and degradation in the kidney.

The tissue distribution and route of clearance of human recombinant interleukin 1 alpha (IL 1 alpha) injected intravenously in rats was studied. The plasma half-life was approximately 2.5 min, and this was increased after nephrectomy, the kidney being the major organ through which the IL 1 alpha was excreted. Two iodinated fragments of IL 1 alpha, of approximately 5 and 9 kDa, were excreted by the kidneys whereas only intact, 17-kDa IL 1 alpha was detected in plasma, suggesting that the protein was being degraded after uptake by the kidney. The results of in vivo experiments in which surface endopeptidase-24.11 was inhibited with phosphoramidon and in vitro experiments in which rat kidney homogenates were incubated with radiolabeled IL 1 alpha suggest that the cytokine was endocytosed and then hydrolysed by lysosomal proteinases.

Animals↗
PubMed1990

The relationship between the circulating concentrations of interleukin 6 (IL-6), tumor necrosis factor (TNF) and the acute phase response to elective surgery and accidental injury.

The possible role of Interleukin 6 (IL-6) and tumour necrosis factor (TNF) in the regulation of the acute phase response to injury was studied in thirteen subjects undergoing elective surgery or suffering from multiple accidental injuries. The temporal changes in the circulating concentrations of these cytokines were related to the circulating acute phase protein concentrations (C-reactive protein and alpha 1 antichymotrypsin), white cell count, blood loss and duration of surgery. Circulating acute phase protein concentrations rose in all subjects during a thirty hour period following injury but none of the subjects showed a detectable rise in circulating concentrations of TNF. Peak circulating concentrations of IL-6 were detected between 4-6 hours after surgery/trauma but these showed a poor correlation with blood loss, fever, white cell count or duration of surgery. The peak concentrations of IL-6 typically occurred before the rise in circulating acute phase protein concentration. The data do not suggest a role for circulating TNF in the regulation of the acute phase response to injury. In contrast, IL-6 appears to be variably involved in the acute phase response but its precise role in mediating fever, leucocytosis and synthesis of acute phase proteins is as yet uncertain.

Acute-Phase Proteins↗
PubMed1989

Development and application of radioimmunoassays for interleukin-1 alpha and interleukin-1 beta.

Specific and sensitive radioimmunoassay (RIA) systems for human IL-1 alpha and IL-1 beta, using sheep polyclonal antisera, have been developed. The assays, which do not require prior extraction of IL-1, have been used to quantify IL-1 alpha and IL-1 beta in synovial fluid and plasma and to quantify intracellular and extracellular IL-1 alpha and IL-1 beta produced by human monocytes stimulated with endotoxin.

Animals↗
PubMed1989

Autoregulation of interleukin 1 production.

Interleukin 1 (IL 1) alpha and beta are distinct cytokines with a common receptor on target cells. Both have been implicated in immunity, inflammation and connective tissue metabolism. Their production is stimulated by microbial products and also by other cytokines derived from accessory cells and lymphocytes. Following reports that IL 1 can stimulate its own production, we have tested the effects of recombinant IL 1 on the synthesis and release of IL 1 alpha and beta by human blood mononuclear cells (MNC). We confirmed that autoinduction occurs but report also the novel finding that this effect is very concentration dependent. At some concentrations within the range found in vivo, recombinant IL 1 not only failed to stimulate further IL 1 production but also inhibited the background level of synthesis in 20-h MNC cultures. The negative feedback appears unrelated to prostaglandin E2 and interferon-gamma levels and could not be reproduced by adding transforming growth factor beta. This previously unrecognized autoregulation may be relevant to clinical diseases associated with pathogenic over-production of IL 1.

Animals↗
PubMed1989

The International Standard for Endotoxin: evaluation in an international collaborative study.

An ampouled preparation of bacterial endotoxin, coded 84/650, was evaluated in 35 laboratories in 12 countries for its suitability to serve as the International Standard for Endotoxin. The ampouled preparation was calibrated in terms of the USA National Standard, EC5, in Limulus Amoebocyte Lysate gelation, turbidimetric and chromogenic tests and in rabbit pyrogen tests. On the basis of the results reported here, with the agreement of the participants in the study, and with the authorization of the Expert Committee on Biological Standardization of the World Health Organization, the preparation coded 84/650 was established in 1986 as the International Standard for Endotoxin for Limulus Gelation Tests with an assigned unitage of 14,000 IU of endotoxin per ampoule.

Animals↗
PubMed1988

Association of the Drosophila melanogaster engrailed protein with specific soluble nuclear protein complexes.

The Drosophila engrailed protein which contains a homeobox domain and specific DNA binding activity is believed to function in the regulation of gene expression during embryogenesis. Here we show that the engrailed protein interacts stably with specific complexes of soluble nuclear proteins when expressed artificially in a cell line and in the developing embryo. The engrailed complexes have molecular masses between 10(7) and 10(8) which suggests they contain a polymeric protein component. The complex is able to bind reversibly to DNA and a definitive purification shows it to be constituted of 12 distinct protein species, two of which are predominant. Purified, bacterially produced engrailed protein can be reconstituted with both culture cell and embryo nuclear protein fractions to form complexes of the same and related composition respectively. On the basis of these results we propose that protein--protein interactions as well as DNA binding are important for correct engrailed protein function in vivo.

Animals↗
PubMed1988

Investigation by HPLC of the catabolism of recombinant tissue plasminogen activator in the rat.

The catabolism of recombinant tissue plasminogen activator (rt-PA) was investigated after injection of radiolabelled material into rats. Both Iodogen and Chloramine T iodination procedures yielded similar biological activity loss in the resultant labelled rt-PA and had half lives in the rat circulation of 1 and 3 min respectively. Complex formation of rt-PA was investigated by HPLC gel exclusion (TSK G3000 SW) fractionation of rat plasma samples taken 1-2 min after 125I-rt-PA injection. A series of radiolabelled complexes of varying molecular weights were found. However, 60% of the counts were associated with a single large molecular weight complex (350-500 kDa) which was undetectable by immunologically based assays (ELISA and BIA) and showed only low activity with a functional promoter-type t-PA assay. Two major activity peaks in the HPLC fractions were associated with free t-PA and a complex having a molecular weight of approximately 180 kDa. HPLC fractionation to produce these three peaks at various timed intervals after injection of 125I-rt-PA showed each to have a similar initial rate half life in the rat circulation of 4-5 min. The function of these complexes as yet is unclear but since a high proportion of rt-PA is associated with a high molecular weight complex with a short half life in the rat, we suggest that the formation of this complex may be a mechanism by which t-PA activity is initially regulated and finally cleared from the rat circulation.

Animals↗
PubMed1988

Interleukin-1 beta as a potent hyperalgesic agent antagonized by a tripeptide analogue.

Interleukin-1 (IL-1) describes two inflammatory proteins, IL-1 alpha and IL-1 beta, produced by activated macrophages and other cell types and encoded by two genes. Their amino acid sequences have only 26% similarity, but their biological activities are comparable, with a few exceptions; indeed, both molecules appear to act at the same receptor. As IL-1 release prostaglandins which sensitize nociceptors in man and in experimental animals, we tested IL-1 alpha and IL-1 beta in rats for hyperalgesic (nociceptive) activity. Our results show that IL-1 beta given systemically is an extremely potent hyperalgesic agent with a probable peripheral site of action; IL-1 alpha is approximately 3,000 times less active than IL-1 beta. We have delineated the region of IL-1 beta mediating the hyperalgesic effect and developed an analgesic tripeptide analogue of IL-1 beta which antagonizes hyperalgesia evoked by IL-1 beta and by the inflammatory agent carrageenan.

Amino Acid Sequence↗
PubMed1988

Inner city deprivation and medical education: a survey of medical students by medical students.

A total of 330 preclinical and clinical medical students and house officers at St Mary's Hospital were surveyed by questionnaire to assess their knowledge and experience of inner city deprivation and health, and their opinions on the role of the doctor in responding to these problems. The response rate was 87%. Over 75% of the respondents had had no experience of inner city living conditions before coming to medical school, and they gained little experience during the medical course until well into the clinical years. Most preclinical students wanted more contact with the community early in the course; less than one-third of the clinical students wanted this. The differences in knowledge and attitudes between the year groups are discussed and possible reorientation in medical education is considered.

Attitude of Health Personnel↗
PubMed1988

The international standard for atrial natriuretic factor. Calibration by an international collaborative study.

An ampouled preparation of human atrial natriuretic factor, ANF-(99-126), was evaluated by 23 laboratories in 10 countries for its suitability to serve as the international standard for ANF. The preparation was calibrated by radioimmunoassay, radioreceptor binding assay, and bioassay and was shown to have satisfactory stability and biological activity. Estimates of the ANF content of a set of specimens of plasma in terms of the standard showed agreement in ranking order when the ANF was extracted prior to assay. However, estimates of the ANF content of the plasmas in terms of either the international standard or the various local standards varied widely among laboratories. On the basis of the results reported here, with the agreement of the participants in the study and with the authorization of the Expert Committee on Biological Standardization of the World Health Organization, the preparation coded 85/669 was established in 1987 as the international standard for ANF, with a defined potency of 2.5 international units per ampoule.

Atrial Natriuretic Factor↗