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Biomedical subjects

D E Woolley

Publications and source records attributed to D E Woolley.

At least 91 records · Page 5Linked to original sources
PubMed1988

Demonstration of histamine H2 receptors on human melanoma cells.

Histamine induced a concentration-dependent increase in intracellular cyclic-AMP of the two human melanoma cell lines SK23 and DX3.LT5.1; maximal stimulation was obtained with 17.8 microM histamine which consistently produced greater than 50-fold increases in the cyclic AMP content of both cell lines. The dose-response curve for histamine in each culture was progressively displaced to the right with increasing concentrations of the histamine H2 receptor antagonist cimetidine. Ranitidine, another H2 receptor antagonist also prevented the histamine-induced cyclic AMP elevation, but the H1 receptor antagonists mepyramine and tripelennamine had no significant effect. These findings indicate that human melanoma cells express histamine H2 receptors, stimulation of which activates adenylate cyclase with a subsequent rise in intracellular cyclic AMP. Mast cell:melanoma interactions mediated by histamine in vivo might therefore be expected to modify some aspects of melanoma cell behaviour.

Adenylyl Cyclases↗
PubMed1988

Effect of recombinant cytokines on glycolysis and fructose 2,6-bisphosphate in rheumatoid synovial cells in vitro.

Recombinant-derived human interleukin 1 (IL1) alpha and beta and interferon gamma (IFN-gamma) each produced similar increases in rheumatoid synovial cell (RSC) glycolysis, as judged by increased values for glucose uptake, lactate production and cellular fructose 2,6-bisphosphate [Fru(2,6)P2]. Measurement of Fru(2,6)P2 proved to be the most sensitive parameter for an assessment of glycolysis: IL1 alpha, IL1 beta and IFN-gamma all produced a 3-6-fold increase in this metabolite whereas tumour necrosis factor (TNF alpha) was far less effective. Prostaglandin E production was stimulated predominantly by IL1 alpha and IL1 beta rather than by IFN-gamma or TNF alpha. When combinations of cytokines were examined the addition of IFN-gamma with either IL1 alpha, IL1 beta or murine IL1 produced a synergistic increase in cellular Fru(2,6)P2. The three forms of IL1 increased Fru(2,6)P2 via the same pathway, whereas IFN-gamma acted via a different mechanism. The increase in Fru(2,6)P2 in subcultured RSC produced by addition of medium from a primary culture exceeded the maximal effects of any of the single cytokines studied, suggesting the presence of a mixture of cytokines in the primary RSC culture medium.

Arthritis, Rheumatoid↗
PubMed1988

Comparative effects of interleukin 1 and a phorbol ester on rheumatoid synovial cell fructose 2,6-bisphosphate content and prostaglandin E production.

The addition of either recombinant human interleukin 1 (IL1 alpha) or 12-O-tetradecanoyl phorbol-13-acetate (TPA) to cultured rheumatoid synovial cells (RSC) caused dose-related increases in PGE production and cellular fructose 2,6-bisphosphate (Fru-2,6-P2). IL1 consistently produced the greater increases in both parameters. A close association between increases in PGE production and Fru-2,6-P2 was demonstrated for both IL1- and TPA-stimulated cells. The combined addition of IL1 with TPA resulted in an additive increase in both parameters. When IL1 was added together with human recombinant interferon-gamma (IFN-gamma), the resulting Fru-2,6-P2 level was synergistically increased, whilst the combination of IFN-gamma and TPA produced only an additive increase. Thus despite their very similar effects on RSC in culture, the data suggests that IL1 and TPA do not act via an identical intracellular mechanism.

Cells, Cultured↗
PubMed1987

Comparative studies of adherent rheumatoid synovial cells in primary culture: characterisation of the dendritic (stellate) cell.

Primary cultures of adherent rheumatoid synovial cells contain variable proportions of fibroblasts, macrophages, and dendritic cells, as judged by morphological appearance. Comparative studies using various enzymic and histochemical staining procedures showed the dendritic cells to lack many of the characteristic features of macrophages, e.g. the failure to express HLA-DR (Ia) antigen. The dendritic cells and fibroblasts had several similarities, but differed to some extent in their nonspecific esterase activity, phagocytic and proliferative potential. As the proportions of dendritic cells and fibroblasts varied in relation to specific culture conditions, we examined the possibility that these morphologies might represent different functional states rather than distinct cellular origins. Using subcultured synovial fibroblasts with a uniform bipolar appearance, we have shown that exposure to interleukin-1 or mast cell products resulted in a transformation to dendritic morphology. This change in cell shape was prevented by the presence of indomethacin, but was subsequently achieved by the addition of exogenous PGE2. Thus it appears that the latter is the factor that modulates the morphological change of fibroblastic to dendritic cells. This study has also demonstrated the complete and reversible interchange of fibroblast/dendritic morphology, thereby confirming that these different shapes are manifest by the same cell. The changes in phenotypic expression associated with the dendritic appearance include increased production of collagenase, prostaglandin E, and nonspecific esterase, as well as an apparent inability to exhibit phagocytosis and to proliferate in culture. We conclude from our in vitro studies that the phenotypic behaviour of the synovial fibroblast (or synoviocyte) is very variable and dependent to a large extent upon local stimuli, but the identity and hierarchy of such stimulating and suppressive factors in relation to cellular interactions requires further study.

Antigens, Surface↗
PubMed1987

Histamine H1 receptors on adherent rheumatoid synovial cells in culture: demonstration by radioligand binding and inhibition of histamine-stimulated prostaglandin E production by histamine H1 antagonists.

Histamine H1 receptors have been demonstrated on adherent rheumatoid synovial cells using biochemical and radioligand binding assays in vitro. The addition of histamine (17.8 mumol/l) to nine primary cultures of adherent rheumatoid synovial cells resulted in a two- to 21-fold increase in the production of prostaglandin E (PGE). This increase was inhibited by three H1 receptor antagonists (mepyramine, tripelennamine, and chlorpheniramine) in a dose related manner at concentrations below 10(-6) mol/l. Competitive binding assays with [3H]mepyramine gave ED50 values of approximately 10(-5) mol/l for the three H1 antagonists. H2 receptor antagonists (cimetidine and ranitidine) did not inhibit the histamine induced increase in PGE and did not compete effectively with the binding of H1 antagonists.

Arthritis, Rheumatoid↗
PubMed1987

Evidence for both histamine H1 and H2 receptors on human articular chondrocytes.

Using specific histamine H1 and H2 receptor antagonists, evidence is presented for the existence of both H1 and H2 receptors on human articular chondrocytes in vitro. Stimulation of the H1 receptor by histamine (range 0.18 to 17.8 mumol/l) significantly increased prostaglandin E (PGE) production, while activation of the histamine H2 receptor increased intracellular cyclic adenosine-5'-monophosphate (AMP). The histamine H1 antagonists mepyramine and tripelennamine blocked the histamine induced increase in PGE production, and the H2 antagonists cimetidine and ranitidine prevented the increase in intracellular cyclic AMP. These observations suggest that mast cell-chondrocyte interactions mediated via histamine may contribute to some of the pathophysiological changes observed in joint disease.

Arthritis, Rheumatoid↗
PubMed1986

Histamine stimulates prostaglandin E production by rheumatoid synovial cells and human articular chondrocytes in culture.

Histamine stimulates prostaglandin E (PGE) production by cultures of adherent rheumatoid synovial cells and human articular chondrocytes. When subcultured synovial fibroblasts or human articular chondrocytes were "primed" by preincubation with conditioned media from primary adherent rheumatoid synovial cell cultures (synovial factor), each produced even higher PGE levels upon histamine exposure. This histamine stimulation was prevented by histamine H1, but not H2, antagonists and was more marked if serum was absent from the culture media. Thus, histamine-induced PGE production by these cells is mediated via H1 receptor activation and subsequent arachidonic acid liberation.

Arthritis, Rheumatoid↗
PubMed1986

Mast cells and matrix degradation at sites of tumour invasion in rat mammary adenocarcinoma.

Significant numbers of mast cells have been demonstrated histologically around the periphery of the invasive rat mammary adenocarcinoma 13672NF. The number of mast cells at microfoci along the tumour:host tissue junction was significantly greater than that found in normal mammary tissues, and few mast cells were detected within the tumour itself. Mast cell degranulation, often associated with disruption and lysis of the connective tissue matrix, was a common feature in later stages of tumour proliferation. When soluble products derived from purified rat peritoneal mast cells were added to monolayer cultures of rat stromal fibroblasts or tumour cells they stimulated a significant increase in total collagenase production, and the mast cell products were also capable of activating the latent collagenases thus produced. Histological examination indicated that degradation of local collagenous matrix was a common feature of mast cell degranulation, an observation possibly explained by the release of mast cell enzymes and/or the potential of this cell to modulate the expression of collagenolytic activity by surrounding cells. These observations suggest that, at least in some tumours, mast cells contribute to the connective tissue breakdown commonly associated with tumour invasiveness and metastatic spread.

Adenocarcinoma↗
PubMed1986

Sex differences in [3H]-estradiol binding in brain and pituitary after acute dopaminergic treatment. In vivo studies in the rat.

Responses to estrogen differ between the sexes, yet sex differences in specific binding of estradiol (E2) to its receptor are not observed consistently. Dopaminergic treatment has been shown to increase binding of 3H-E2 in selected brain areas and anterior pituitary in the female rat, and the dopaminergic system is sexually differentiated. In order to determine whether or not dopaminergic stimulation might induce sex differences in 3H-E2 binding, male and female gonadectomized-adrenalectomized rats were pretreated either with bromocriptine, a dopamine agonist, or with diethyldithiocarbamate (DDC), an inhibitor of dopamine beta-hydroxylase. DDC was used in order to increase endogenous release of dopamine. After such acute dopaminergic treatment, specific binding of 3H-E2 in nuclear and extranuclear fractions of 6 brain areas and pituitary in vivo was determined 1 h after intravenous injection of 3H-E2 (1 microgram/kg body weight). Administration of either bromocriptine or DDC increased specific 3H-E2 binding to nuclear and extranuclear fractions of basal hypothalamus and anterior pituitary from female but not from male rats, thus inducing sex differences in binding in these two tissues. Bromocriptine also increased specific binding in the pineal in females. Total binding was increased in a crude membrane fraction (P2) from pituitary of female but not of male rats after administration of DDC, but the percent of extranuclear specific binding found in the P2 fraction was decreased after DDC in both males and females. The findings suggest that dopaminergic stimulation may induce sex differences in 3H-E2 binding by increasing binding in some brain areas and anterior pituitary in females but not in males.

Animals↗
PubMed1985

Mast-cell products and heparin stimulate the production of mononuclear-cell factor by cultured human monocyte/macrophages.

Purified mast cells derived from rat peritoneal fluids and dog mastocytomas were extracted with 1 M-NaCl and sonication techniques. The mast-cell products increased the production of mononuclear cell factor from human peripheral blood mononuclear cells in culture, as judged by the enhanced stimulation of prostaglandin E (2-5 fold) and collagenase (3-11-fold) production by cultured adherent synovial cells. Heparin alone (1-10 micrograms/ml) induced a similar stimulation of mononuclear-cell-factor production by monocyte cultures, whereas histamine (1-10 micrograms/ml) had no effect. The stimulatory effect of mast-cell products and heparin represented a direct effect on mononuclear cells; they did not potentiate the effect of monokine on the synovial cells. These results suggest that mast-cell-macrophage interactions may play a significant role in the pathogenesis of inflammation and connective-tissue degradation.

Cells, Cultured↗
PubMed1985

Histamine H2 receptors on chondrocytes derived from human, canine and bovine articular cartilage.

Histamine (1-100 microM) induced a concentration-dependent increase in intracellular cyclic AMP in monolayer cultures of human, canine and foetal-bovine articular chondrocytes. The dose-response curve for histamine in each culture was progressively displaced to the right with increasing concentrations of cimetidine, an H2-receptor antagonist. The histamine-induced cyclic AMP elevation in human articular chondrocytes was also significantly decreased by ranitidine, another H2 antagonist, but not by the H1 antagonists mepyramine and chlorpheniramine. These findings indicate that histamine activates chondrocyte adenylate cyclase through an H2 receptor. The cyclic AMP response of human chondrocytes to histamine was many times greater than that measured for synovial fibroblasts under similar conditions. Such findings suggest that mast-cell-chondrocyte interactions in vivo may contribute to changed chondrocyte metabolism in joint disease.

Animals↗
PubMed1985

Bidirectional erosion of cartilage in the rheumatoid knee joint.

Specimens of cartilage with contiguous bone and overlying synovial pannus were obtained from 22 rheumatoid knee joints and examined histologically using specific histochemical staining techniques. All showed significant erosions of cartilage by synovial cells, but seven specimens also showed substantial cartilage erosion by cells from the subchondral bone region. This bidirectional attack on rheumatoid knee cartilage did not represent an 'underpinning' of cartilage by synovial pannus, as judged by serial sectioning and the identification of specific cells. Whereas cartilage-pannus junctions had mainly macrophagic or fibroblastic cells, cartilage-bone lesions were usually characterised by chondroclasts and blood vessels. Lymphocytes were generally absent from all sites of cartilage erosion. The bidirectional attack on articular knee cartilage suggests that changes have occurred within the cartilage that make it vulnerable to cellular invasion and erosion. Such changes might reflect a deficiency in 'anti-invasion factors', or the exposure of hidden epitopes and subsequent immunogenicity, or a combination of both.

Arthritis, Rheumatoid↗
PubMed1984

All three chains of 1 alpha 2 alpha 3 alpha collagen from hyaline cartilage resist human collagenase.

A previous report that the 3 alpha collagen chain of hyaline cartilage was cleaved by human collagenase could not be confirmed when the 1 alpha 2 alpha 3 alpha collagen fraction was freed of all contaminating type II collagen. All three minor collagen chains, 1 alpha, 2 alpha and 3 alpha, were totally resistant to highly purified collagenases from both rheumatoid synovial and gastric mucosal tissues. This finding and CNBr-peptide patterns suggest that, despite the close homology with alpha 1 (II), the 3 alpha chain is a unique collagen component, possibly combined with 1 alpha and 2 alpha in heterotrimeric molecules. In contrast, a 3 alpha-like component from fibrocartilage was cleaved by collagenase and gave a CNBr-peptide pattern more typical of alpha 1 (II) than of the collagenase-resistant 3 alpha of hyaline cartilage.

Animals↗
PubMed1984

Histopathology of the rheumatoid lesion. Identification of cell types at sites of cartilage erosion.

Histochemical and ultrastructural techniques were used to examine the cartilage-pannus junction of 49 rheumatoid joints. Whereas 24 showed relatively acellular, fibrous pannus tissue, 25 demonstrated "cellular" junctions with different cell types at sites of erosion. Macrophages and fibroblasts were commonly observed as majority cell types in most specimens, but others showed mast cells, polymorphonuclear leukocytes, dendritic, or plasma cells as the predominant cell type. Some showed local accumulations of different cell types at sites along each junction. Our findings show that the cellular composition at sites of cartilage erosion varies greatly and suggest that cells are subject to turnover and interchange.

Arthritis, Rheumatoid↗
PubMed1984

Chondroclasts and osteoclasts at subchondral sites of erosion in the rheumatoid joint.

Histochemical and ultrastructural studies of bone-cartilage junctions from 21 rheumatoid knee joints have demonstrated the presence of both osteoclasts and chondroclasts. Significant erosions of bone and mineralized cartilage were observed in 15 specimens, and 6 showed localized erosions of unmineralized (hyaline) cartilage. Chondroclasts, defined by their close association with both mineralized and unmineralized cartilage, were morphologically and histochemically similar to osteoclasts. Our observations suggest that these multinucleate cells play a crucial role in subchondral tissue destruction, but that erosion of unmineralized cartilage is primarily the result of synovial pannus tissue.

Acid Phosphatase↗
PubMed1984

Collagenolytic mechanisms in tumor cell invasion.

Connective tissue stroma and basement membrane structures probably present natural barriers to the migration of tumor cells. It has therefore been proposed that collagenolytic enzymes are required to facilitate the spread and invasion of tumor cells into host tissues. The collagenases and cathepsin B-like enzymes are thought to be involved, but the cellular source of collagenolytic activity at the tumor: host interface or 'invasion zone' remains obscure in most cases. The 'invasion zone' of different tumors is very variable with regard to the type and numbers of host or tumor cells, as well as the type of collagenous matrix, and few generalities can be made. The existence within a tumor of specialised subpopulations of cells which have different metastatic potential has been postulated. As a consequence it seems plausible that the phenotypic expression of highly invasive or metastatic tumor cells should include the potential for generating collagenolytic activity. Immunolocalisation studies have demonstrated the production of type I and type IV collagenases at sites of tumor invasion, but it does not appear to be a continuous process and only a small proportion of tumor and/or host cells elaborate enzyme at any one moment. Collagenase production is invariably microenvironmental in nature and it seems likely that local host:tumor cell interactions are important in modulating collagenolysis. Macrophages and mast cells have been shown to stimulate collagenase expression by tumor and stromal cells in vitro, and it is proposed that these cells may assume a contributory role for the induction of collagenolytic activity in vivo. The collagenolytic mechanisms that operate at micro-foci of host:tumor junctions probably depend upon the type of collagen, the cellular composition and the extracellular ionic conditions of each invasion site. Either tumor or host cells may elaborate enzymes, this being dependent upon the type and/or tissue location of the invasive tumor.

Animals↗
PubMed1984

Morphometric effects of exposure to lead during the preweaning period on the hippocampal formation of aging rats.

Our previous morphologic studies in the rat demonstrated that exposure to lead during the preweaning period induced delays in the maturation of late-developing regions of the hippocampal formation at 15 days of age, followed by normal development or hypertrophy of the same areas in young adulthood. The present study was carried out to determine whether or not subtle or latent effects of such exposure to lead may be unmasked with the additional challenge of aging. To do this, mid-dorsal sections of the hippocampal formation from middle-aged (578-631 days old) Long-Evans control rats and from rats exposed to lead from birth until weaning via dams drinking 0.2% lead acetate were analyzed by light and electron microscopy. Exposure to lead did not alter areas of either neuropil or neuronal layers of the hippocampus or the dentate gyrus or the numbers per section or numerical densities (numbers per unit area) of neurons in hippocampal CA3 stratum pyramidale or dentate stratum granulosum. It did reduce mean size of complex invaginated mossy fiber synapses without altering their numbers in the proximal (close to dentate gyrus) mossy fiber zone, which was the zone also affected at 15 and 90 days of age in our previous studies.

Age Factors↗