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Biomedical subjects

A Horner

Publications and source records attributed to A Horner.

35 records · Page 2Linked to original sources
PubMed1996

Production of collagenase by human osteoblasts and osteoclasts in vivo.

Studies in some animal species have demonstrated the production of metalloproteinases by bone cells, suggesting that they may play a role in bone modeling and remodeling. The aim of the present study was to investigate the expression of collagenase in human bone in situ, using heterotopic and osteophytic bone. Immunohistochemistry was performed on chilled sections of bone, using well characterized polyclonal antibodies to human collagenase. The heterotopic and osteophytic bone exhibited high turnover and both bone modeling and remodeling were evident. Collagenase expression by osteoblasts was demonstrated in cells synthesising matrix and in lining cells; the strongest signal was seen in areas of de novo matrix formation, where bridges of woven bone were being formed between areas of mineralized bone. Collagenase was also present in some osteoclasts associated with eroded bone surfaces and in some mononuclear cells that were present in resorption cavities and in the bone marrow. Our results provide the first demonstration, in situ, of collagenase in human bone and suggest that it may play a role in human bone modeling and remodeling. Production of collagenase by active osteoblasts and lining cells suggest that it may be involved both in matrix formation and activation of bone remodeling. The presence of collagenase in osteoclasts provides further evidence that metalloproteinases may play a role in bone resorption.

Acid Phosphatase↗
PubMed1996

Distribution of platelet-derived growth factor (PDGF) A chain mRNA, protein, and PDGF-alpha receptor in rapidly forming human bone.

Platelet-derived growth factors (PDGFs) are potent bone cell mitogens which stimulate the proliferation of osteoblastic cells, may also be involved in the regulation of osteoclastic bone resorption, and indirectly induce vascular endothelial cell proliferation and angiogenesis. In view of the established relationship between angiogenesis and osteogenesis, the production of PDGFs by both osteoblastic and vascular endothelial cells suggests that they may play a role in bone formation during skeletal development. We have used two human models of rapid bone formation, heterotopic bone and osteophytic bone, to investigate the expression of PDGF-A mRNA and protein and the PDGF-alpha receptor protein in vivo using in situ hybridization and immunohistochemistry. PDGF-A mRNA and protein were widely distributed throughout heterotopic and osteophytic bone. Within the cartilaginous tissue PDGF-A mRNA and protein were most strongly expressed by mature chondrocytes with decreased expression in the hypertrophic zone and almost no staining in the mineralizing and mineralized zones. PDGF mRNA and protein were also expressed in cells of small blood vessels within fibrous and cartilaginous tissue. In contrast, PDGF-alpha receptor expression was restricted to a minority of hypertrophic chondrocytes and sites of vascular invasion. Within the bone and fibrous tissue the growth factor and the receptor were widely distributed, being detected on most cells at sites of bone formation or in remodeling sites; no receptor was detected on osteoclasts. These data demonstrate the widespread expression of PDGF-A and its receptor in forming human bone and indicate that this growth factor may exert autocrine and paracrine effects to regulate osteogenesis during skeletal development.

Bone Development↗
PubMed1995

CD40-CD40 ligand (CD40L) interactions and X-linked hyperIgM syndrome (HIGMX-1).

Interactions between the B cell surface antigen CD40 and its ligand (CD40L) expressed on activated T cells play a critical role in isotype switching. This is illustrated by failure of isotype switching in patients with X-linked hyperIgM syndrome in whom the CD40L gene is mutated and by failure of isotype switching of CD40-deficient mice in response to T-cell-dependent antigens. We review these findings and discuss the signaling mechanisms of CD40 and the developmental control and transcriptional regulation of CD40L expression.

Animals↗
PubMed1995

Localization of viable bacteria and bacterial antigens in arthritic joints of Erysipelothrix rhusiopathiae-infected pigs.

Chronic polyarthritis was induced in pigs by infection with Erysipelothrix rhusiopathiae (serovar 2, strain T28). Viable bacteria could be reisolated as long as 5 months post-infection from synovial fluid, synovial tissue and from isolated chondrocytes. The number of viable bacteria could be increased by hypotonic shock of the chondrocytes indicating a substantial intracellular amount of bacteria. Bacterial antigens were shown by immunohistochemistry to be present on the surface of both chondrocytes and synovial cells in arthritic joints. Neither viable bacteria nor bacterial antigen were detected in unaffected joints.

Animals↗
PubMed1995

Bacterial superantigens induce the proliferation of resting gamma/delta receptor bearing T cells.

We observe that highly purified (> or = 97% pure) gamma/delta T cells isolated from normal peripheral blood proliferate to bacterial toxin supperantigens SEA, SEB, SED, and TSST-1. MHC class II molecules were necessary and sufficient for the recognition of superantigens by gamma/delta T cells because MHC Class II deficient B cell line failed to support the proliferation of gamma/delta T cells to toxins and murine L cells transfected with HLA-DR but not untransfected cells were capable of presenting toxins to gamma/delta T cells. As in the case with alpha/beta T cells, bacterial superantigens synergized with PMA in causing the proliferation of purified gamma/delta T cells rigorously depleted of accessory cells. Together, our findings suggest that gamma/delta T cells recognize and respond to bacterial superantigens in a manner similar to alpha/beta T cells.

Animals↗
PubMed1995

Chondrocyte-peripheral blood mononuclear cell interactions: the role of ICAM-1.

Chondrocytes express a number of cell-surface molecules that mediate cell-cell or cell-matrix interactions. The expression of intercellular adhesion molecule-1 (ICAM-1) by chondrocytes under inflammatory conditions has been well documented. Here we demonstrate the involvement of ICAM-1-, CD18- and RGD-dependent adhesion mechanisms in chondrocyte-T-cell adhesion and in cell-mediated killing of chondrocytes in vitro. In the absence of cytokine stimulation, chondrocyte-peripheral blood mononuclear cell (PBMC) interactions were unaffected by inhibition of ICAM-1-dependent pathways but were significantly reduced by blockade of CD18- and RGD-dependent pathways. Following cytokine stimulation chondrocyte-PBMC adhesion and chondrocyte killing were significantly increased. These effects could be inhibited by the blockade of ICAM-1.

Animals↗
PubMed1994

Intercellular adhesion molecule-1 (ICAM-1) and MHC class II on chondrocytes in arthritic joints from pigs experimentally infected with Erysipelothrix rhusiopathiae.

This study set out to investigate the in vivo expression and distribution of the porcine homologues of the intercellular adhesion molecule-1 (ICAM-1) and MHC Class II as markers of chondrocyte activation during the development of chronic polyarthritis, which was experimentally induced in Landrace pigs by intra-articular injection of Erysipelothrix rhusiopathiae. ICAM-1 was found to be strongly expressed in vivo on chondrocytes and synovial cells in arthritic joints but was not detected in cartilage from unaffected joints. Although the majority of ICAM-1 positive chondrocytes did not co-express MHC Class II, chondrocyte-type cells expressing both molecules were detected in the transition zone as the disease progressed, particularly at 5 months post-infection. At this stage infiltration of CD4+ T lymphocytes into the damaged cartilage was also apparent. ICAM-1 and MHC Class II are not constitutively expressed on porcine chondrocytes but appeared to be induced as arthritis progressed. The detection of these markers in the pig helps to establish the validity of this animal model for immunopathological studies.

Animals↗
PubMed1994

Cyclosporin A inhibits CD40 ligand expression in T lymphocytes.

The ligand for CD40 is expressed on activated T lymphocytes and delivers contact-dependent activation signals to B lymphocytes. The mechanisms regulating CD40 ligand gene expression are largely unknown. Optimal expression of CD40 ligand required activation of protein kinase C and a rise in intracellular calcium concentration. CD40 ligand expression was inhibited by pretreatment of T cells with cyclosporin A. Cyclosporin A analogues inhibited CD40 ligand expression with a potency mirroring the ability of each compound to inhibit calcineurin activity, indicating that calcineurin plays a key role in CD40 ligand gene expression. Cyclosporin A inhibited IL-4-driven CD40 ligand-dependent IgE isotype switching in PBMC but did not inhibit IgE synthesis induced by CD40 mAb plus IL-4. PBMC derived from transplant patients receiving cyclosporin A failed to express CD40 ligand upon stimulation. These results suggest that patients receiving cyclosporin A may be deficient in CD40 ligand-dependent T cell help.

Adolescent↗
PubMed1994

Upregulation of complement regulators MCP (CD46), DAF (CD55) and protectin (CD59) in arthritic joint disease.

CD46, CD55 and CD59 are cell surface glycoproteins which are widely distributed on normal tissue, where they function in the prevention of complement-mediated damage. In this study we have investigated the altered expression of these molecules under inflammatory conditions both in vitro and in vivo. By using immunocytochemical techniques we demonstrated marked but disparate upregulation of these molecules in IL1-treated cartilage and in diseased cartilage from arthritic joints compared to normal cartilage in both humans and pigs. Expression of these proteins was restricted to the chondrocyte surface, and was also demonstrated on isolated chondrocytes grown in monolayer culture and stimulated with IL1. It is suggested that the elevated levels of these regulatory proteins may be necessary to ameliorate the multiple damaging effects of the inflammatory processes associated with destructive joint diseases.

Adult↗
PubMed1992

Detection of cytokine activated chondrocytes in arthritic joints from pigs infected with Erysipelothrix rhusiopathiae.

Chronic polyarthritis was induced in pigs by injection of Erysipelothrix rhusiopathiae and the in vivo activation of chondrocytes by cytokines was then investigated in the affected joints by immunocytochemistry. A polyclonal antiserum which recognises surface markers on in vitro interleukin 1 activated porcine chondrocytes was used to detect activated chondrocytes in all zones of the cartilage from diseased joints. In contrast, cartilage removed from an unaffected joint in the same animal showed no chondrocyte activation. Inflammatory synovial tissue removed from diseased joints and cocultured with cartilage from the unaffected joint induced activation of adjacent chondrocytes. The presence of interleukin 1 in the inflammatory cells of the synovium was confirmed and major histocompatibility complex (MHC) class II antigens were detected as a marker of synovial activation. Chondrocytes were found not to express class II antigens in cartilage from either the diseased or the unaffected joint. These observations show that the porcine erysipelas model of arthritis will be useful in facilitating a novel approach to monitoring the behaviour of individual chondrocytes under pathophysiological conditions.

Animals↗
PubMed1991

The sensitivity of synthesis of human cartilage matrix to inhibition by IL-1 suggests a mechanism for the development of osteoarthritis.

The damage to articular cartilage, characteristic of arthritic disease, is usually ascribed to increased degradative activity by enzymes or free radicals from locally activated cells. We propose that inhibition of matrix synthesis, and consequential impairment of the natural repair process, may be at least as important in chronic joint disease.

Adolescent↗
PubMed1991

Recognition of IL1-activated chondrocytes in porcine articular cartilage.

A polyclonal antiserum has been raised against interleukin 1 (IL1)-induced epitopes on the surface of porcine articular chondrocytes. Using this antiserum in immunolocalization studies we have been able to identify individual chondrocytes in situ both in experimentally activated articular cartilage and in pathological tissue from pigs with induced polyarthritis.

Animals↗
PubMed1991

Immunorecognition of chondrocytes in articular cartilage activated by synovial interleukin 1.

A polyclonal antiserum which recognizes surface epitopes on IL1-activated pig chondrocytes has been used to immunolocalize chondrocytes responding to IL1 produced during co-culture of pig synovium and articular cartilage. Activation of the chondrocytes by the cytokine was restricted to the articular and subarticular region of the cartilage adjacent to the synovium. Chondrocyte activation was also seen when human rheumatoid synovium was co-cultured with the cartilage. The presence of IL1 in some synovial cells was confirmed by immunolocalization using antisera specific for IL1 alpha and IL1 beta.

Animals↗
PubMed1988

150 years of mapping Ireland's population distribution.

"Over the last 150 years various approaches to the construction of maps showing the distribution of population in Ireland have been explored. This article reviews these approaches, and is particularly intended to illustrate how the compilers of Irish population maps have confronted that central issue facing all cartographers, namely the selection of an appropriate level of generalisation."

Demography↗
PubMed1985

Leydig cell damage after testicular irradiation for lymphoblastic leukaemia.

The effect of testicular irradiation on Leydig cell function has been studied in a group of boys irradiated between 1 and 5 years earlier for a testicular relapse of acute lymphoblastic leukaemia. Six of the seven boys irradiated during prepubertal life had an absent testosterone response to HCG stimulation. Two of the four boys irradiated during puberty had an appropriate basal testosterone level, but the testosterone response to HCG stimulation was subnormal in three of the four. Abnormalities in gonadotrophin secretion consistent with testicular damage were noted in nine of the 11 boys. Evidence of severe Leydig cell damage was present irrespective of whether the boys were studied within 1 year or between 3 and 5 years after irradiation, suggesting that recovery is unlikely. Androgen replacement therapy has been started in four boys and will be required by the majority of the remainder to undergo normal pubertal development.

Adolescent↗