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Biomedical subjects

S R Goldring

Publications and source records attributed to S R Goldring.

72 records · Page 4Linked to original sources
PubMed1984

Rheumatoid synovial cell hormone responses modulated by cell-cell interactions.

Cellular interactions within the rheumatoid synovium are likely to be responsible for the destructive properties of this tissue. The responses to hormones which regulate connective tissue metabolism may also be influenced by these cell-cell interactions. To determine the effect of cellular interactions on responses to hormones, human peripheral blood mononuclear cells were cocultured with adherent rheumatoid synovial cells. Coculture resulted in a decrease in response to prostaglandin E2 as assessed by a reduction in the magnitude of the acute prostaglandin-induced cyclic AMP response. In contrast, coculture resulted in an increase in the magnitude of the acute parathyroid hormone-induced cyclic AMP response. The decrease in response to prostaglandin was reversed by the presence of indomethacin during the preincubation, whereas indomethacin had no effect on the cyclic AMP response to parathyroid hormone. Increases in endogenous synovial cell prostaglandin production (stimulated by soluble factors released by the mononuclear cells) accounted for the subsequent decrease in the response to exogenous prostaglandin. The increase in cyclic AMP response to parathyroid hormone could not be explained by a soluble factor and was independent of ambient prostaglandin levels.

Arthritis, Rheumatoid↗
PubMed1984

Heparin modulates intracellular cyclic AMP in human trabecular bone cells and adherent rheumatoid synovial cells.

Cells were cultured from explants of human trabecular bone excised from eight patients and incubated usually for 20 minutes with bovine parathyroid hormone, salmon calcitonin, prostaglandin E2, or heparin. The intracellular content of cyclic AMP was measured by radioimmunoassay and was significantly increased by parathyroid hormone in four, by calcitonin in two, by prostaglandin E2 in eight, and by heparin in seven out of eight cultures. In the two cultures containing calcitonin-responsive cells heparin inhibited the cyclic AMP response induced by calcitonin. Heparin did not affect the cyclic AMP response to parathyroid hormone or prostaglandin E2. Heparin also increased the cyclic AMP content of cultured adherent rheumatoid synovial cells. It is proposed that, in certain situations of focal pathological bone resorption, although concentrations of circulating hormones may be normal, the local release of products such as heparin may modify the effect of hormones which regulate connective tissue homoeostasis. local changes in hormone responses could contribute to the enhanced bone resorption associated with inflammatory processes such as rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed1984

A system for culture of human trabecular bone and hormone response profiles of derived cells.

Specimens of human trabecular bone from II patients were processed for tissue culture. In 10 out of 11 samples both cellular and matrix outgrowths were noted at the surfaces of explanted fragments after the first week in culture. During the second week adherent cells extended beyond the margins of the bone fragments and appeared to replicate. Plates achieved confluence in 30-36 days and cells were subcultured. In passaged cells doubling times were 5-7 days. Six cell cultures were examined for the presence of alkaline and acid phosphatase activity employing histochemical techniques. All six cultures contained cells which stained positively for alkaline phosphatase (10-80%). A small number of cells in one culture demonstrated tartrate-resistant acid phosphatase activity. Responses to hormones known to regulate the biological activities of skeletal tissues were also tested. Intracellular cyclic AMP was significantly increased by parathyroid hormone in three cultures, by salmon calcitonin in three cultures and by prostaglandin E2 in all 10 cultures. All three hormones increased the cyclic AMP content of cells cultured from human periosteum. It is concluded that cells cultured by this method demonstrate biochemical and morphological characteristics consistent with a skeletal tissue origin. Furthermore, such an approach may permit isolation and further characterization of individual subpopulations of bone cells of human origin.

Acid Phosphatase↗
PubMed1983

The synovial-like membrane at the bone-cement interface in loose total hip replacements and its proposed role in bone lysis.

UNLABELLED: The membrane present at the bone-cement interface was retrieved from twenty patients with a loose, non-septic failed total hip replacement at a site clearly remote from the pseudocapsule that reformed postoperatively. The orientation of the membrane was carefully marked to identify the surface in contact with cement. The membrane was studied histologically, histochemically, by cell culture, by organ culture, and by assessment of its ability to synthesize prostaglandin E2 and collagenase. This membrane, rather than being a nondescript so-called fibrous membrane, has the histological and histochemical characteristics of a synovial-like lining. The synovial-like cells are adjacent to the cement layer. Deep to them macrophages predominate. Inflammatory cells are absent. Cell cultures of this membrane contain stellate cells similar to those found in cell cultures of normal and rheumatoid synovial tissue. This membrane has the capacity to produce large amounts of prostaglandin E2 and collagenase. CLINICAL RELEVANCE: This transformation of tissue at the bone-cement interface in patients with a non-septic, loose total hip component to a synovial-like tissue with the capacity to generate prostaglandin E2 and collagenase may explain the progressive lysis of bone that is seen in some patients with loose cemented total joint implants. Loosening of the component may be a stimulus to the synthetic activity of this tissue, which leads to further resorption of bone. Understanding and the possibility of pharmacological control of this membrane may contribute to improved duration of total joint implants.

Bone Resorption↗
PubMed1981

Factors modulating the response of a porcine renal tubular cell line to calcitonin and antidiuretic hormone.

A cell line (LLC-PK1) isolated from porcine kidney increases 3'5'-cyclic adenosine monophosphate (cAMP) content when incubated with salmon calcitonin (SCT) or antidiuretic hormone (ADH). We have examined several factors which modulate the hormone-induced changes in cAMP levels in these cells. Preincubation with increasing concentrations of SCT results in a dose-dependent decrease in cAMP levels in cells retested with this hormone. Addition of 3-isobutyl-l-methylxanthine (IBMX) to cells preincubated with SCT results in 15--30-fold increases in cAMP levels compared to cells preincubated without this hormone. These observations suggest that the decrease in SCT-induced cAMP response in cells pretreated with this hormone is related at least in part to stimulation of phosphodiesterase activity. Preincubation with ADH does not affect subsequent cAMP response to either ADH or SCT, suggesting that these hormones interact with different cell surface receptors. Cell cycle and plating density also affect cAMP levels. cAMP content per cell increases with increasing cell density, which is associated with an increase in the SCT-induced cAMP response. These studies illustrate that factors other than receptor occupancy modulate cAMP responses of these cells to specific hormones.

1-Methyl-3-isobutylxanthine↗
PubMed1981

Factors regulating the response of cells cultured from human giant cell tumors of bone to parathyroid hormone.

Exposure of cells cultured from human giant cell tumors of bone to parathyroid hormone (PTH) results in an increase in the intracellular cAMP content. When cells are preincubated with PTH for periods as short as 10 min and then reexposed to this hormone, there is a decrease in the subsequent PTH-induced cAMP response. This decrease is inversely related to the concentration of PTH present during the preincubation. To investigate the factors responsible for this decrease in hormone response, we used a synthetic substituted analog of bovine PTH, [Nle8, Nle18, Tyr34]bPTH-(3-34) amide (PTH-Inh), which had previously been shown to be a competitive inhibitor of PTH-induced cAMP response in renal and bone-derived tissues. Incubation of these cultured cells with this analog failed to increase intracellular cAMP levels. In contrast to the results obtained with native hormone, when cells were preincubated with PTH-Inh, the acute cAMP response to native PTH after the removal of PTH-Inh was not diminished. In addition, simultaneous preincubation with native PTH and PTH-Inh partially overcame desensitization to PTH. These results suggest that occupancy of the PTH receptor alone is not sufficient to cause desensitization. Rather, steps subsequent to hormone binding, including activation of adenylate cyclase, may be required for the induction of a state of desensitization to PTH.

1-Methyl-3-isobutylxanthine↗
PubMed1979

Regulation of hormone-induced cyclic AMP response to parathyroid hormone and prostaglandin E2 in cells cultured from human giant cell tumors of bone.

Cells dispersed from human giant cell tumors of bone and grown in monolayer culture increase intracellular cyclic AMP (cAMP) when incubated with parathyroid hormone (PTH) or prostaglandin E2 (PGE2). When cells are continuously exposed to PTH, cAMP levels increase acutely but then decrease rapidly to pretreatment values despite continued presence of hormone or addition of new hormone. Preincubation of cells with PTH for periods as short as 10 min results in a decrease in the capacity of cells to increase cAMP content when re-exposed to maximal stimulatory concentrations of PTH. The decrease in the magnitude of the PTH-induced cAMP response observed in cells pretreated with this hormone is dependent on the concentration of PTH present during the preincubation. The loss of cAMP response in cells pretreated with either PGE2 or PTH is hormone specific in that cells made refractory by pretreatment with one hormone still increase cAMP content when exposed to the other. Although the cells are not releasing measurable amounts of prostaglandins into the medium, pretreatment with indomethacin results in an increase in the magnitude of the cAMP response to PGE2. The PTH-induced cAMP response is not affected by indomethacin pretreatment. The loss of PTH responsiveness produced by hormone preincubation is consistent with the phenomenon of "down-regulation" observed with ligand-receptor interactions in a variety of tissues.

1-Methyl-3-isobutylxanthine↗
PubMed1979

Collagenase and prostaglandin in connective tissue destruction: cell-cell and humoral interactions.

Connective tissue destruction is a major characteristic of chornic rheumatoid arthritis (RA). This process is accompanied by local cellular and humoral inflammatory reactions. Long-term cultures of adherent synovial cells (ASC) from patients with RA produce large amounts of collagenase and prostaglandin (PGE2), two substances that play a role in the degradation of joint structures. Lvels of collagenase and PGE2 can be stimulated (up to several hundred-fold) with a soluble factor (MCF) from cultured peripheral blood mononuclear cells (MW approximately 14,000). The monocyte-macrophages alone produce MCF but can be stimulated directly with Fc fragments of immunoglobulin or concanavalin A to increase MCF production. Addition of T lymphocytes in the presence of lectin or antigen significantly enhances the production of MCF. MCF affects other biological processes in synovial cells such as the rate of collagen synthesis, cell proliferation and sensitivity to PGE2 as well as collagen itself can further modulate collagenase release by the synovial cells and function in an amplificative loop. The understanding of these interactions between cells, mediator-effector substances and connective tissue substrates may provide a basis for devising more rational approaches to therapy of the destructive lesions which characterize RA.

Arthritis, Rheumatoid↗
PubMed1978

Response to hormones of cells cultured from human giant cell tumors of bone.

Giant cell tumors of bone obtained from 7 patients were dispersed with clostridial collagenase and trypsin and adherent cells were maintained in culture. Early cultures contained both mononucleated and multinucleated cells presumably derived from the stromal and giant cells of the original tumor. The original multinucleated cells did not survive for greater than 7-10 days whereas the mononucleated cells persisted and could be passaged by trypsinization. In 5 of 7 early cultures exposed to parathyroid hormone (PTH) there was a rise in cAMP within 5-10 min in both cells and medium which averaged approximately 12-fold. None of the cells responded to calcitonin and a variable rise in cAMP was seen after incubation with prostaglandin E2. In cells cultured from 3 tumors the PTH response disappeared with passage of the cells, but in the remaining 2, PTH response persisted through multiple passages. The presence as well as the magnitude of the PTH-induced cAMP response in these cells is consistent with a skeletal origin.

Adult↗