Biomedical subjects

S Poole

Publications and source records attributed to S Poole.

At least 109 records · Page 6Linked to original sources

PubMed1994

Lipopolysaccharide induces sickness behaviour in rats by a vagal mediated mechanism.

To assess the possibility that lipopolysaccharide (LPS) induces sickness behaviour by activating primary afferent nerves, the effects of LPS (1.25 mg kg-1, intraperitoneally) were compared in vagotomized and sham-operated rats. Subdiaphragmatic vagotomy blocked the LPS-induced depression of social investigation but had no effect on LPS-induced increases in levels of IL-1 beta in plasma and peritoneal macrophages and on LPS-induced changes in dehydrogenase activity of peritoneal macrophages.

Animals↗

PubMed1993

The international standard for interleukin-6. Evaluation in an international collaborative study.

Three ampouled preparations of interleukin-6 (IL-6) were evaluated by 12 laboratories in seven countries for their suitability to serve as the international standard of IL-6. The preparations were assayed using in vitro bioassays and immunoassays. 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 (ECBS) of the World Health Organization (WHO) one of the preparations (coded 89/548) was established as the international standard of IL-6.

Biological Assay↗

PubMed1993

Development of a two-site immunoradiometric assay for rat/human corticotrophin-releasing factor. Application to the measurement of interleukin-1 beta-stimulated production of hypothalamic CRF in vitro.

The hypothalamic hormone corticotrophin-releasing factor (CRF) is a highly conserved, 41-residue peptide, the N terminal region of which rarely induces antibody production, which has hindered the development of two-site immunometric assays. A synthetic N terminal peptide, CRF1-20-Cys-Tyr-NH2, was conjugated to bovine serum albumin through the cysteine thiol group, and used to prepare N terminal directed CRF-specific antibodies. The same peptide, conjugated through the cysteine thiol group to activated thiol-Sepharose, was used to affinity purify N terminal CRF-specific antibodies, and these were used in conjunction with a radioiodinated C terminal directed monoclonal anti-CRF antibody for the development of a specific, sensitive two-site immunoradiometric assay for CRF. To test the utility of the assay, hypothalami were stimulated in vitro with interleukin-1 beta, a putative regulator of CRF secretion, and CRF was measured in hypothalamic homogenates and conditioned media. Interleukin-1 beta dose-dependently stimulated synthesis and secretion of CRF, demonstrating the applicability of the immunoradiometric assay, and confirming previous reports that interleukin-1 beta can directly stimulate CRF secretion from the rat hypothalamus in vitro.

Amino Acid Sequence↗

PubMed1993

Bradykinin release of TNF-alpha plays a key role in the development of inflammatory hyperalgesia.

Using specific antisera for IL-1 beta and IL-8, as well as cyclooxygenase inhibitors and propranolol, we have demonstrated that these cytokines are responsible for the prostaglandin and sympathetic components of carrageenin-induced hyperalgesia in the rat paw test. The release of IL-1 beta and IL-8 is preceded by the liberation of TNF-alpha. We have also tested in a nociceptive model the effects of bradykinin and a specific bradykinin antagonist, HOE 140, on the hyperalgesia induced by carrageenin and lipopolysaccharide (LPS). Bradykinin-induced hyperalgesia was abolished by HOE 140 and by treatment of the paws with anti-TNF-alpha antisera. HOE 140 significantly inhibited the hyperalgesia induced by carrageenin and LPS. It is suggested that in these two models bradykinin is associated with the release of hyperalgesic cytokines.

Animals↗

PubMed1993

Cutaneous markers of internal malignancy. I. Malignant involvement of the skin and the genodermatoses.

Cutaneous findings often reflect the presence and course of an internal disease. Recognition of external clues is important to facilitate both early diagnosis and prompt treatment of the internal disorder. Early recognition is especially valuable in a patient with an internal malignant disease because intervention may significantly affect survival. In this two-part series, we review the spectrum of cutaneous markers of internal malignancy. Part I focuses on malignant involvement of the skin caused by either direct extension or metastases and the genodermatoses with malignant potential. Part II will be devoted to the paraneoplastic skin manifestations of internal malignancy as well as environmental carcinogens that produce cutaneous features. We also discuss some proposed but controversial associations between skin disease and internal malignancy.

Chromosome Aberrations↗

PubMed1993

Cutaneous markers of internal malignancy. II. Paraneoplastic dermatoses and environmental carcinogens.

A variety of cutaneous disorders may reflect the presence of an internal disease. The ability to recognize those that may indicate an underlying malignancy is of particular importance. In part I of this series malignant involvement of the skin, either direct or metastatic, and the genodermatoses with malignant potential were reviewed. In this portion, we describe the paraneoplastic dermatoses as well as the cutaneous effects of some environmental carcinogens associated with internal malignancy. In addition, several uncommon and controversial associations between benign dermatoses and internal malignant disease will be discussed.

Carcinogens, Environmental↗

PubMed1993

Bradykinin initiates cytokine-mediated inflammatory hyperalgesia.

1. The hyperalgesic activities in rats of bradykinin, carrageenin and lipopolysaccharide (LPS) were investigated in a model of mechanical hyperalgesia. 2. Bradykinin and carrageenin evoked dose-dependent hyperalgesia with maximum responses of similar magnitude to responses to LPS (1 and 5 micrograms). 3. Hoe 140, an antagonist of BK2 receptors, inhibited in a dose-dependent manner hyperalgesic responses to bradykinin, carrageenin and LPS (1 microgram) but not responses to LPS (5 micrograms), prostaglandin E2, dopamine, tumour necrosis factor alpha (TNF alpha), IL-1, IL-6 and IL-8. 4. Responses to bradykinin and LPS (1 and 5 micrograms) were inhibited by the cyclo-oxygenase inhibitor, indomethacin and by the beta-adrenoceptor antagonist, atenolol. The effects of indomethacin and atenolol were additive: their combination abolished responses to bradykinin and LPS (1 microgram) and markedly attenuated the response to LPS (5 micrograms). 5. Antiserum neutralizing endogenous TNF alpha abolished the response to bradykinin whereas antisera neutralizing endogenous IL-1 beta, IL-6 and IL-8 each partially inhibited the response. The combination of antisera neutralizing endogenous IL-1 beta+IL-8 or IL-6+IL-8 abolished the response to bradykinin. 6. Antisera neutralizing endogenous TNF alpha, IL-1 beta, IL-6 and IL-8 each partially inhibited responses to LPS (1 and 5 micrograms). Increasing the dose of antiserum to TNF alpha or giving a combination of antisera to IL-1 beta+IL-8 or IL-6+IL-8 further inhibited responses to LPS (1 and 5 micrograms). 7. These data show that bradykinin can initiate the cascade of cytokine release that mediates hyperalgesic responses to carrageenin and endotoxin (1 microgram). The lack of effect of Hoe 140 on hyperalgesic responses to LPS (5 microgram) suggests that the release of hyperalgesic cytokines can be initiated independently of bradykinin BK2 receptors.

Animals↗

PubMed1993

Immunocytochemical localization of inflammatory cytokines and vascular adhesion receptors in radicular cysts.

Odontogenic cysts are one of the commonest bone destroying lesions of the maxillofacial skeleton, with the inflammatory radicular cyst being the commonest jaw cyst. Explants of radicular cysts produce an interleukin-1-like activity which could explain the osteolysis seen with these tumours though the cellular source of this osteolytic activity is unknown. In the present study, cytokines with known inflammatory and osteolytic activity: interleukin-1 (IL-1), tumour necrosis factor (TNF), interleukin-6 (IL-6), and the chemotactic cytokine interleukin-8 (IL-8) have been localized immunocytochemically in radicular cysts. The cellular adhesion receptors ICAM-1 and ELAM-1 have also been immunolocalized. All specimens showed positive staining for IL-1 (alpha and beta) and IL-6, with these cytokines being located in epithelial and vascular endothelial cells. Only two specimens demonstrated TNF and IL-8 staining, which was located in macrophages. All specimens demonstrated ELAM-1 staining in endothelium and ICAM-1 staining in epithelium, endothelium and mononuclear cells. These findings show that radicular cysts contain two bone-modulating cytokines, IL-1 and IL-6, and that these appear to be synthesized mainly by the epithelial cells. Cysts also contain a proportion of activated blood vessels whose endothelial cells express the cellular adhesion receptors ICAM-1 and ELAM-1.

Alveolar Bone Loss↗

PubMed1993

The value of screening for diabetes in patients with skin sepsis.

Four hundred and eighty-two patients with spontaneous skin and superficial sepsis and 291 controls of similar age and sex underwent random capillary blood glucose measurements in order to assess whether screening for diabetes in patients presenting with skin sepsis to an Accident & Emergency Department detects a greater number of cases than that present in the background population. All subjects with a concentration > 7.8 mmol/l were subsequently followed up with a 75 g oral glucose tolerance test. Forty-two (8.7%) of the 482 skin sepsis patients had a capillary blood glucose > 7.8 mmol/l compared to eight (2.7%) of the 291 without sepsis (chi 2 = 9.71, P < 0.002). Of these, 26 of the skin sepsis group and 7 of the control group attended for follow up. Of those who attended, 13 of the skin sepsis group had an abnormal glucose tolerance test (seven diabetes, six impaired glucose tolerance-IGT) compared to two (one diabetes, one IGT) of the control group (chi 2 = 2.87, P < 0.1). The difference in cases of frank diabetes between the two groups was not statistically significant. Of the total eight diabetic cases identified, five (on direct questioning) had symptoms of hyperglycaemia (thirst, polyuria and/or weight loss) and two of the others were obese, one of whom had documented ischaemic heart disease. Thus, while most cases of diabetes in patients with skin sepsis could be detected by specifically asking about hyperglycaemic symptoms and performing a blood glucose estimation when these are present, we suggest that the screening of patients with skin sepsis over 40 years of age provides an opportunistic method of screening. This strategy should yield clinically significant numbers of abnormal cases.

Adolescent↗

PubMed1993

Endotoxin-stimulated production of rat hypothalamic interleukin-1 beta in vivo and in vitro, measured by specific immunoradiometric assay.

Regulation of a number of aspects of the acute-phase response, including induction of fever and activation of the hypothalamo-pituitary-adrenal axis, occurs within the hypothalamus. The acute-phase response appears to be co-ordinated by the inflammatory cytokine interleukin-1 (IL-1). A number of studies using hybridization techniques to measure IL-1 gene expression and immunocytochemistry to localize immunoactive IL-1 have established the concept that the central nervous system, and in particular the hypothalamus, is a site of IL-1 production, and that levels increase in response to inflammatory stimuli. In this report we present data on the levels of IL-1 beta produced in the rat hypothalamus using quantitative immunoassay techniques. Bacterial endotoxin, administered to rats in vivo, evoked increases in hypothalamic IL-1 beta levels which were significant within 1 h, and reached maximum levels at 5-10 h. The response to endotoxin was dose-related, and levels reached in hypothalamic extracts corresponded to intrahypothalamic levels of the order of 20 ng/ml. During short-term in-vitro culture of rat hypothalami, endotoxin stimulated a dose-related increase in both the synthesis and the secretion of IL-1 beta, which reached similar levels to those seen after in-vivo stimulation. Hypothalami obtained from animals stimulated with endotoxin in vivo did not, however, show any evidence of persistent stimulation of IL-1 beta production when subsequently cultured in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Corticotrophin-releasing factor as a mediator of the acute-phase response in rats, mice and rabbits.

The acute-phase response involves a number of separate physiological components, including induction of acute-phase protein synthesis by the liver. This response can be induced in vivo by administration of the endogenous leucocytic mediator interleukin-1 beta. A number of in-vivo effects of interleukin-1 beta have been reported to be mediated by corticotrophin-releasing factor (CRF), including activation of the hypothalamo-pituitary-adrenal axis and induction of fever, and in this report we have examined a possible involvement of CRF in mediating interleukin-1 beta-induced acute-phase protein synthesis. Interleukin-1 beta stimulated the elevation of species-specific plasma acute-phase proteins in rats, mice and rabbits. Co-injection of interleukin-1 beta with the specific CRF receptor antagonist alpha-helical-CRF9-41NH2 abolished or attenuated acute-phase protein synthesis induced by interleukin-1 beta in all three species for up to 12 h after injection. The inhibitory effect of alpha-helical-CRF9-41NH2 was reduced or absent 24 h after injection. Neutralizing anti-CRF antisera had no effect on acute-phase protein synthesis in the mouse and, paradoxically, potentiated acute-phase protein synthesis induced by interleukin-1 beta in the rat. These results indicate a possible mediatory role for CRF in regulation of acute-phase protein synthesis, and suggest that CRF may mediate induction of acute-phase protein synthesis by a different mechanism from that involved in regulation of corticotrophin secretion.

Acute-Phase Proteins↗

PubMed1993

A requirement not to be overlooked. Nutritional aspects of respiratory disease.

For many people with severe respiratory disease malnutrition can become a major problem. By considering the practical and physical difficulties caused by the respiratory symptoms and more accurately assessing nutritional needs, an inadequate dietary intake can be overcome, leading to a better nutritional status.

Enteral Nutrition↗

PubMed1992

Immunosuppressive activity of corticotrophin-releasing factor. Inhibition of interleukin-1 and interleukin-6 production by human mononuclear cells.

Corticotrophin-releasing factor (CRF) from the hypothalamus stimulates corticotrophin (ACTH) secretion. Concentrations of CRF in the peripheral circulation are normally low, and increase during pregnancy due to CRF secretion by the placenta [Cunnah, Jessop, Besser & Rees (1987) J. Endocrinol. 113, 123-131], although CRF in maternal blood does not appear to stimulate the hypothalamo-pituitary-adrenal (HPA) axis [Potter, Behan, Fischer, Linton, Lowry & Vale (1991) Nature (London) 349, 423-426]. We have examined the possibility that the placental. CRF might contribute to the suppression of the maternal immune system, which is necessary to prevent rejection of the foetus, by studying endotoxin-evoked cytokine production by monocytes as a model for activation of the immune response. CRF inhibited endotoxin-evoked cytokine production from human mononuclear cells (MNCs), the fraction of peripheral blood containing monocytes. The effects of CRF were reversed by a specific CRF receptor antagonist, and were additive with glucocorticoid inhibition of cytokine secretion. Anti-interleukin-1 (IL-1) antisera inhibited endotoxin-evoked IL-6 production; however, the CRF effect was not additive, suggesting that CRF inhibition of IL-6 production may be secondary to CRF inhibition of IL-1. These results suggest a role for CRF as an immunosuppressant during pregnancy.

Cells, Cultured↗

PubMed1992

Peripheral analgesic activities of peptides related to alpha-melanocyte stimulating hormone and interleukin-1 beta 193-195.

1. The hyperalgesic effects of interleukin-1 beta (IL-1 beta) and prostaglandin E2 (PGE2) were measured in rats. 2. Hyperalgesic responses to IL-1 beta were inhibited in a dose-dependent manner by alpha-melanocyte stimulating hormone (alpha-MSH)-related peptides with the following order of potency: [N1(4),D-Phe7]alpha-MSH greater than alpha-MSH greater than Lys-D-Pro-Val greater than Lys-Pro-Val greater than Lys-D-Pro-Thr greater than D-Lys-Pro-Thr. 3. Hyperalgesic responses to PGE2 were not inhibited by Lys-D-Pro-Thr and D-Lys-Pro-Thr but were inhibited in a dose-dependent manner by the other peptides with the same order of potency as against IL-1 beta. 4. The potencies of [N1(4), D-Phe7]alpha-MSH and alpha-MSH were greatly diminished by deletion of their C-terminal tripeptide, Lys11-Pro-Val13. 5. Nor-binaltorphimine (Nor-BNI) largely reversed the analgesic effects of alpha-MSH, [N1(4), D-Phe7]alpha-MSH, Lys-Pro-Val and Lys-D-Pro-Val indicating that kappa-opioid receptors mediated the analgesic activity of these peptides. 6. Nor-BNI did not antagonize the inhibition by Lys-D-Pro-Thr and D-Lys-Pro-Thr of IL-1 beta evoked hyperalgesia indicating that these peptides were not acting via kappa-opioid receptors.

Amino Acid Sequence↗

PubMed1992

The pivotal role of tumour necrosis factor alpha in the development of inflammatory hyperalgesia.

1. The hyperalgesic activities in rats of interleukin-1 beta (IL-1 beta), IL-6, IL-8, tumour necrosis factor alpha (TNF alpha) and carrageenin were investigated. 2. IL-6 activated the previously delineated IL-1/prostaglandin hyperalgesic pathway but not the IL-8/sympathetic mediated hyperalgesic pathway. 3. TNF alpha and carrageenin activated both pathways. 4. Antiserum neutralizing endogenous TNF alpha abolished the response to carrageenin whereas antisera neutralizing endogenous IL-1 beta, IL-6 and IL-8 each partially inhibited the response. 5. The combination of antisera neutralizing endogenous IL-1 beta + IL-8 or IL-6 + IL-8 abolished the response to carrageenin. 6. These results show that TNF alpha has an early and crucial role in the development of inflammatory hyperalgesia. 7. The delineation of the role of TNF alpha, IL-1 beta, IL-6 and IL-8 in the development of inflammatory hyperalgesia taken together with the finding that the production of these cytokines is inhibited by steroidal anti-inflammatory drugs provides a mechanism of action for these drugs in the treatment of inflammatory hyperalgesia.

Animals↗

PubMed1991

The effect of interleukin-1 on venous endothelium--an ultrastructural study.

The effect of systemic interleukin-1 (IL-1) on venous endothelium in the presence and absence of stasis has been studied by scanning electron microscopy (SEM). Recombinant human IL-1 beta at a concentration of 1 micrograms/kg or saline was injected intravenously into rabbits and allowed to circulate for 0.5 or 4.0 h after which complete stasis was induced for 1 h in an isolated segment of each jugular vein. One vein segment was then excised and the contents examined macroscopically for thrombi, while the other segment was fixed for SEM examination. When examined by SEM the endothelium from rabbits injected with IL-1 beta was perturbed with increased surface microvilli, blebs and gaps at cell junctions when compared with saline controls. Fibrin deposition was also observed after IL-1 beta, as was the adherence of essentially non-activated platelets to intact endothelium. However, macroscopic thrombi were not formed in isolated vein segments. We conclude that although fibrin strands and platelets were deposited on the endothelium, IL-1 is not a sufficiently powerful procoagulant stimulus to lead to an occlusive thrombus in acute experiments.

Animals↗

PubMed1991

Measurement of cytokine production by the monocytic cell line Mono Mac 6 using novel immunoradiometric assays for interleukin-1 beta and interleukin-6.

Immunoradiometric assays for interleukin-1 beta and interleukin-6 were developed using affinity-purified IgG fractions from antisera initially raised for radioimmunoassay. Capture and detector functions were carried out by the same antibody preparation within each assay. The assays were precise, rapid and 6-8-fold more sensitive than the RIA systems previously employed. IRMAs were used for the initial characterisation of a candidate cell line (Mono Mac 6), under investigation in a 'monocyte test' for pyrogen detection, and permitted rapid and specific determination of the cytokines under stimulatory and inhibitory conditions.

Animals↗

PubMed1991

Influence of tumor-derived interleukin 1 on melanoma-endothelial cell interactions in vitro.

Human melanoma cell lines that express high constitutive levels of the metastasis-associated marker intercellular adhesion molecule 1 (ICAM-1) were found to secrete interleukin 1 (IL-1) in vitro. Experiments with neutralizing antibodies showed that this cytokine was responsible for their expression of ICAM-1 but not that of two other progression/metastasis markers, Muc-18 and Gp IIb/IIIa. The IL-1 present in melanoma-conditioned medium induced the expression of vascular cell adhesion molecule 1, endothelial-leukocyte adhesion molecule 1, and ICAM-1 on human umbilical vein endothelial cells (ECs) in culture and increased the rate at which melanoma cells and ECs adhered to each other. IL-1-producing melanoma lines adhered significantly more rapidly to ECs than did non-IL-1-producing lines, and this enhancement was reduced by prior incubation of the melanoma cells with neutralizing anti-IL-1 antibodies. Similarly, endothelial cells treated with conditioned medium from IL-1-producing melanoma lines adhered significantly more rapidly to melanoma cells than did ECs treated with medium from non-IL-1-producing melanoma lines, and this enhancement was abolished by addition of anti-IL-1 antibodies to EC cultures in conditioned medium. Blocking antibodies to endothelial vascular cell adhesion molecule 1, endothelial-leukocyte adhesion molecule 1, and ICAM-1 failed to inhibit melanoma-EC adhesion, but an antibody to tumor cell GpIIb/IIIa did block adhesion by up to 44%. The ability to secrete IL-1 could increase the metastatic potential of melanoma cells by stimulating tumor cell-EC adhesion.

Antigens, CD↗