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Biomedical subjects

M Turner

Publications and source records attributed to M Turner.

At least 217 records · Page 12Linked to original sources
PubMed1989

Regulation of expression of human IL-1 alpha and IL-1 beta genes.

IL-1 gene expression was investigated in human blood mononuclear cells. IL-1 alpha and IL-1 beta mRNA were induced with LPS or TNF. Kinetic measurements on Northern blots revealed that these stimuli elicited qualitatively similar changes in IL-1 mRNA levels, and that expression of IL-1 mRNA was transient. IL-1 beta mRNA was the predominant mRNA species and remained elevated for somewhat longer than IL-1 alpha mRNA. TNF and IFN-gamma synergized to induce both species of IL-1 mRNA and IL-1 bioactivity. Transcriptional control, as measured by nuclear run on assays, partly determines the greater levels of IL-1 beta mRNA because the rate of IL-1 beta transcription was greater than that of IL-1 alpha. Cycloheximide (CHX) was able to induce IL-1 mRNA but did not induce transcription of either IL-1 gene. When added to cultures pretreated with TNF or LPS, CHX superinduced IL-1 mRNA, but IL-1 transcription was not increased. If added simultaneously CHX blocked TNF-induced IL-1 gene transcription, suggesting that TNF may induce factors required for IL-1 gene transcription. CHX increased the stability of both IL-1 alpha and IL-1 beta mRNA, demonstrating the existence of a post-transcriptional form of control. In half-life experiments IL-1 beta mRNA was more stable than IL-1 alpha mRNA, indicating that post-transcriptional control also contributes to the greater steady state levels of IL-1 beta. Taken together, the available evidence suggests IL-1 alpha and IL-1 beta mRNA are regulated differentially at both the transcriptional and post-transcriptional level.

Cycloheximide↗
PubMed1989

Tumor necrosis factor mediates autocrine growth inhibition in a chronic leukemia.

Autocrine production of growth factors may contribute to the rapid and fatal proliferation of acute hematologic malignancies. We have investigated whether the more controlled growth of less aggressive malignancies such as chronic myeloid leukemia (CML) may be associated with autocrine production of growth inhibitory factors. TNF inhibits the growth of both normal and leukemic hemopoietic progenitor cells. We find that exogenous TNF reduces the viability and DNA synthesis of purified myeloid cells from patients with CML and inhibits myeloid colony formation by patient progenitor cells. However, unlike progenitor cells from normal donors, patient myeloid progenitor cells also constitutively express mRNA for TNF and secrete functional TNF protein in culture. This endogenous TNF impedes the growth of CML cells because anti-TNF mAb shown to neutralize bioactive human TNF increases CML cell DNA synthesis whereas non-neutralizing anti-TNF mAb has no effect. Production of TNF by CML cells is not associated with production of lymphotoxin (TNF-beta), IL-1 or IL-6. TNF-mediated autocrine growth inhibition may contribute to the maintenance of the stable, chronic phase of this disease and similar mechanisms may operate in other malignancies to limit tumor proliferation. Competition between autocrine growth promoting and inhibiting factors may underlie the observed differences in biologic behavior between acute and chronic malignancies.

Antibodies, Monoclonal↗
PubMed1989

Modulation of cytokine production by transforming growth factor-beta.

Transforming growth factor-beta 1 (TGF-beta 1) is one of a family of polypeptides involved in the regulation of cell growth and differentiation. The effects of human rTGF-beta 1 on the production of IL-1 and TNF by activated PBMC were studied. The addition of TGF-beta 1 alone caused an increase in the levels of mRNA for IL-1 alpha, IL-1 beta, and TGF-alpha. This was due to increased transcription rather than enhanced mRNA stability. The induced mRNA were of the appropriate size as assessed by Northern blotting. However, the mRNA did not appear to be translated into protein, inasmuch as the translation products of IL-1 beta and TNF-alpha were not detected by RIA or ELISA. Furthermore, in experiments utilizing a neutralizing antibody to TGF-beta 1, we were unable to unmask IL-1 biologic activities and unable to detect TNF biologic activity in the WEHI 164 cytotoxicity assay. TGF-beta inhibited in a dose-dependent manner the induction of IL-1 beta by LPS or TNF but not by PHA and PMA. Similarly, LPS induction of TNF-alpha was blocked by TGF-beta, whereas induction of PMA and PHA was completely resistant. TGF-beta 1 did not increase PGE2 secretion or cause elevated intracellular cAMP; thus, the inhibitory effects of TGF-beta 1 seem not to be mediated by PGE2 or cAMP, which have both been implicated in post-transcriptional control of cytokine gene expression. These findings suggest a dual role for TGF-beta 1 in the regulation of cytokine production at both transcriptional and translational levels.

Adjuvants, Immunologic↗
PubMed1989

Interleukin 7 (murine pre-B cell growth factor/lymphopoietin 1) stimulates thymocyte growth: regulation by transforming growth factor beta.

The effects of interleukin 7 (IL7) previously known as murine pre-B cell growth factor/lymphopoietin 1 on the growth of murine thymocytes was investigated. In the presence of a suboptimal dose of phytohemagglutinin, IL7 induced a dose-dependent increase in thymocyte proliferation which was comparable to that induced by IL1. Additionally IL7 was shown to synergize with a suboptimal dose of IL1 to enhance thymocyte proliferation. Thymocyte proliferation induced by IL7, like that induced by IL1, was inhibited when either recombinant transforming growth factor (TGF) beta 1 or beta 2 were added at the initiation of culture. Interestingly, IL7-driven thymocyte proliferation was considerably less susceptible to inhibition by TGF-beta 1 or TGF-beta 2 than that induced by IL1. Taken together these results suggest IL7 may activate distinct populations of thymocytes and/or act through a pathway distinct from that utilized by IL1.

Animals↗
PubMed1989

Intrathyroidal cytokine production in thyroid disease.

The intrathyroidal production of Interferon gamma, tumour necrosis factor alpha and beta, Interleukin-1 alpha and beta, Interleukin-6, platelet-derived growth factor A and of transforming growth factor-beta was analysed in patients with autoimmune and non-autoimmune thyroid disease. Cytokines were assessed indirectly by slot blot mRNA analysis in fresh tissue samples (unpurified cells, infiltrating mononuclear cells and thyroid follicular cells), in thyroid follicular cells in primary culture, as well as in thyroid-derived T-cell clones. The production of Interleukin-1 alpha and beta, Interleukin-6 and transforming growth factor beta was additionally measured by bioassay. Cytokine production by thyroid-infiltrating mononuclear cells generally did not differ between autoimmune and non-autoimmune samples, the whole panel of all cytokines being found in freshly purified cells as well as in thyroid-derived T-cell clones from patient with Graves' disease, as well as with multinodular non-toxic goitre. Thyroid follicular cells produced Interleukin-1 alpha, Interleukin-6 and transforming growth factor beta. Interleukin-1 and Interleukin-6 production did not differ between thyroid follicular cells from autoimmune and non-autoimmune thyroids. Transforming growth factor beta was, however, lower in non-toxic goitre than in Graves' disease and in normal thyroid tissue, but could be increased by exposure of the cells to micromolar concentrations of iodide. This seemed of special interest, as transforming growth factor beta proved to inhibit thyroid follicular cell growth in response to known growth stimuli, such as insulin-like growth factor I or epidermal growth factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoimmune Diseases↗
PubMed1989

Transforming growth factor beta regulates thyroid growth. Role in the pathogenesis of nontoxic goiter.

The production and growth regulatory activity of transforming growth factor beta were studied in human thyroid tissue. As estimated by its mRNA expression in fresh tissue samples, transforming growth factor beta was produced in normal and in diseased thyroid glands. Transforming growth factor beta mRNA was mainly produced by thyroid follicular cells and in lesser quantities by thyroid infiltrating mononuclear cells. The concentrations of transforming growth factor beta mRNA were lower in iodine-deficient nontoxic goiter than in Graves' disease and normal thyroid tissue. Transforming growth factor beta protein secretion by cultured thyroid follicular cells was also low in nontoxic goiter, but could be increased by addition of sodium iodide (10 microM) to the culture medium. Recombinant transforming growth factor beta did not affect basal tritiated thymidine incorporation in cultured thyroid follicular cells, but inhibited, at a concentration of 10 ng/ml, the growth stimulatory influence of insulin-like growth factor I, epidermal growth factor, transforming growth factor alpha, TSH, and partly that of normal human serum on cultured thyroid follicular cells. This inhibition was greater in Graves' disease than in nontoxic goiter. These results suggest that transforming growth factor beta may act as an autocrine growth inhibitor on thyroid follicular cells. Decreased transforming growth factor beta production and decreased responsiveness to transforming growth factor beta may be cofactors in the pathogenesis of iodine-deficient nontoxic goiter.

Adult↗
PubMed1989

Endothelin-1: contractile responses and autoradiographic localization of receptors in rabbit blood vessels.

Endothelin-1 (ET-1) elicits a contractile response from intact and endothelium-denuded rings of rabbit aorta and carotid artery. At low doses of ET-1, the response is attenuated in the presence of endothelium. The specific receptors that mediate the contractile response are located by autoradiography on the vascular smooth muscle although the decrease in response in intact rings may imply that they are also present on the endothelium.

Animals↗
PubMed1989

Effect of cytokines on HLA-DR and IL-1 production by a monocytic tumour, THP-1.

The monocytic tumour, THP-1, expresses many of the properties of monocytes, both by cell surface staining and its capacity to produce monokines. It was used as a source of homogenous monocytic cells as a model to determine whether a variety of highly purified or recombinant cytokines could induce HLA-DR expression and the production of interleukin-1 (IL-1). Interferon-gamma (IFN-gamma) alone induced HLA-DR. Tumour necrosis factor (TNF), lymphotoxin (LT) and granulocyte-macrophage colony-stimulating factor (GM-CSF) alone were able to induce IL-1 but not HLA-DR. When IFN-gamma was combined with TNF, induction of HLA-DR and IL-1 was enhanced in a synergistic manner. These effects were detectable at a pretranslational level as synergistic effects were observed on DR alpha mRNA and IL-1 beta mRNA levels. The results demonstrate the specificity of IFN-gamma as the inductive stimulus for HLA-DR expression by THP-1 cells. As IFN-gamma and TNF are products of activated T cells, the synergistic role for these molecules in macrophage activation is discussed.

Biological Factors↗
PubMed1989

Analysis of intrathyroidal cytokine production in thyroid autoimmune disease: thyroid follicular cells produce interleukin-1 alpha and interleukin-6.

Cytokine production was studied in thyroid tissue from patients with Graves' disease, Hashimoto's thyroiditis and non-toxic goitre. The expression of interferon gamma, tumour necrosis factor alpha and beta, interleukin-1 alpha and beta, interleukin-6 and platelet-derived growth factor A chain was assessed by slot-blot analysis of the respective mRNA in freshly isolated tissue samples. All seven cytokines were detected in patients of all groups. Although the respective mRNA levels were, in general, higher in thyroid autoimmune disorders, this appeared to relate to the degree of the lymphocytic infiltration of the thyroid gland at the time of surgery. Purified thyroid follicular cells expressed high levels of interleukin-1 alpha and interleukin-6 mRNA and when established in primary culture, purified thyroid follicular cells from Graves' disease as well as non-toxic goitre produced interleukin-1 alpha and interleukin-6 bioactivity spontaneously. In the case of interleukin-1 this could be further augmented by addition of lipopolysaccharide to the thyroid follicular cell cultures. These results demonstrate that the lymphocytic infiltrate found in autoimmune and non-autoimmune thyroid disorders is associated with cytokine production. Additionally we have shown that intrathyroidal cytokine production is not restricted to thyroid-infiltrating mononuclear cells, but may also involve thyroid follicular cells both in vivo and in vitro. The cytokines produced by thyroid follicular cells may have an important role in stimulating autoantigen specific T cells in vivo as both interleukin-1 and interleukin-6 facilitate T cell activation.

Adult↗
PubMed1988

Post-transcriptional control of IL-1 gene expression in the acute monocytic leukemia line THP-1.

The acute monocytic leukemia cell line THP-1 secretes predominantly IL-1 beta after treatment with bacterial lipopolysaccharide and tumour promoting phorbol ester (PMA). IL-1 alpha is also secreted, but represents less than 10% of the total IL-1 activity. This differential is reflected at the level of mRNA as IL-1 beta mRNA is more abundant than IL-1 alpha mRNA. Studies of transcription in isolated nuclei however indicate that each gene is transcribed at a similar rate, suggesting that post-transcriptional mechanisms regulate the relative abundance of IL-1 alpha and IL-1 beta mRNA. Measurement of RNA half life after addition of alpha-amanitin (an inhibitor of RNA polymerase II) indicate that IL-1 alpha mRNA is not as stable as IL-1 beta mRNA suggesting one mechanism for the different relative levels of RNA.

Amanitins↗
PubMed1988

Comparison of patterns of expression of tumour necrosis factor, lymphotoxin and interleukin-6 mRNA.

The expression of the mRNA encoding tumour necrosis factor, lymphotoxin and interleukin-6 by peripheral blood mononuclear cells was analysed. Unstimulated cells contained no detectable mRNA for these cytokines, however each mRNA was transiently expressed after stimulation with either the combination of phytohaemagglutinin and phorbol ester or the single stimulus of lipopolysaccharide. The dual stimulus yielded the stronger signal. The cytokine mRNA's had short half lives, but were stabilised following protein synthesis inhibition. Cyclosporin A completely blocked induction of lymphotoxin and partially inhibited induction of TNF and IL-6 mRNA. The features of regulation described in this paper suggest these genes belong within the "early" set of genes expressed following immune cell activation.

Cycloheximide↗
PubMed1988

Tumour necrosis factor as an autocrine tumour growth factor for chronic B-cell malignancies.

Recombinant tumour necrosis factor (TNF) promotes survival and induces proliferation in the tumour cells from two malignancies of B lymphocytes--hairy-cell leukaemia and B-chronic lymphocytic leukaemia. Culture with TNF also induces TNF mRNA and protein, so the cytokine may act as an autocrine tumour growth factor. These growth promoting effects are antagonised by alpha but not by gamma interferon.

B-Lymphocytes↗
PubMed1988

Home parenteral nutrition: a review of 100 patient years of treatment in 76 consecutive cases.

Over the last 10 years, the Nutrition Unit at Hope Hospital has trained and looked after 76 patients on home parenteral nutrition for a total of 100 patient years. Although 40 per cent of patients have required home parenteral nutrition for 6 months or less one patient has been on treatment for 7 years. The quality of life measured on a 4 point scale was good for the majority of patients. Sepsis and superior vena caval thrombosis are the main problems encountered. Overall mortality rate was 18 per cent and the sepsis rate was 0.14 episodes per patient per year. Home parenteral nutrition is an effective and safe treatment of intestinal failure.

Adolescent↗