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Biomedical subjects

J A Pringle

Publications and source records attributed to J A Pringle.

36 records · Page 2Linked to original sources

Cellular heterogeneity in giant cell tumour of bone (osteoclastoma): an immunohistological study of 16 cases.

Sixteen cases of giant cell tumour of bone (osteoclastoma) were analysed by immunohistochemical techniques using various monoclonal antibodies specific for macrophages, monocytic and granulocytic cells, T- and B-lymphocytes and other cell types. The multinucleate osteoclastic giant cells failed to react with the majority of antibodies specific for myeloid cells and HLA-DR. In contrast to previous findings, giant cells in some tumours reacted with a rat, but not mouse, antibody to leucocyte common (CD45) antigen. Macrophages were detected in all tumours, though their numbers varied considerably; small numbers of T- and B-lymphocytes were identified in four of 16 cases. The neoplastic, spindle-shaped, stromal cells were largely unreactive with the monoclonal antibodies used in this study, further supporting the view that they are not the precursors of the characteristic giant cells, nor are they of haemopoietic origin.

Antibodies, Monoclonal↗

Movement of the shoulder after resection of a tumor of the scapula.

Forty-seven patients who had a tumor of the scapula were seen by the Bone Tumour Panel at the Royal National Orthopaedic Hospital, Stanmore, Middlesex, England. Sixteen resections were performed in fourteen patients. Although other authors have discussed the length of survival of one or a few such patients, none, to our knowledge, has reported on postoperative movement of the shoulder. We correlated the type of resection of bone and muscle with the restrictions of postoperative movement. Our patients had an excellent range of postoperative movement, even after subradical resection. The study enabled us to make recommendations for reconstruction of muscle after resection and to determine the functional prognosis.

Adolescent↗

Calcitonin receptors of human osteoclastoma.

Osteoclast-rich cultures were prepared by disaggregation of osteoclastomas (giant cell tumour of bone) and settlement onto glass or plastic surfaces. Autoradiography using [125I]-salmon calcitonin ([125I]-sCT) revealed specific binding only to multinucleate giant cells (osteoclasts) and a minor population of mononuclear cells. [125I]-sCT competitive binding studies indicated a Kd of 5 x 10(-10) M and receptor number of approximately 1 million sites/osteoclast. sCT treatment resulted in a dose-dependent rise in cAMP (EC50 10(-10) M). Homogenates of an osteoclastoma also demonstrated specific binding of [125I]-sCT. Chemical cross-linking of a labelled synthetic sCT derivative. [125I]-[Arg11,18,Lys14]-sCT, using disuccinimidyl suberate, resulted in labelling of a receptor component of approximate Mr 85-90,000. The multinucleate giant cells (osteoclasts) of human osteoclastomas possess large number of CT receptors which exhibit the same binding kinetics and apparent Mr as those of other CT target cells.

Bone Neoplasms↗

Monoclonal antibodies against osteoclasts inhibit bone resorption in vitro.

Several recently-derived monoclonal antibodies (mcabs) that bind with a high degree of specificity to membrane antigens of osteoclasts were tested for their effects on the function of giant cells from osteoclastomas. None of the antibodies stimulated bone resorption when incubated with giant cells on bone slices, nor did we find any evidence that the mcabs were able to block calcitonin-inhibition of bone resorption. However, three of the mcabs strongly inhibited bone resorption. This inhibition was unaccompanied by impaired survival or morphological evidence of toxicity, but the same mcabs induced a state of cytoplasmic quiescence we have previously found to be characteristic of the response of osteoclasts to local and systemic inhibitors of osteoclastic bone resorption. These results suggest that the mcabs bind to antigens of functional importance in bone resorption or its regulation, and the similarity between the response of giant cells to mcabs and hormonal inhibitors of bone resorption raises the possibility that the mcabs may bind to and cause activation of surface receptors for one or more of these hormones. Whether this is so or not, the mcabs which influence giant cell function may represent valuable probes for an analysis of the mechanism and regulation of osteoclastic bone resorption.

Antibodies, Monoclonal↗

The effects of calcium regulating hormones on bone resorption by isolated human osteoclastoma cells.

Cells were disaggregated from osteoclastomas, and the response of the giant cells to calcium-regulating hormones, prostaglandin (PG)E1 and dibutyryl cyclic AMP (dbcAMP) was observed by phase-contrast time-lapse video microscopy. The pattern and nature of their response was very similar to that previously found to be characteristic of osteoclasts: calcitonin (CT), PGE1 and dbcAMP induced cytoplasmic quiescence, while parathyroid hormone (PTH) showed no influence on cytoplasmic motility or behaviour. The cells were also cultured on slices of devitalized cortical bone for 5 or 18 h. After this time the giant cells were associated with the appearance in the scanning electron microscope of characteristic resorption pits, the volume of which was calculated by computer-assisted morphometric and stereophotogrammetric techniques after removal of cells. Calcitonin caused a dramatic reduction in the volume of bone resorbed by these isolated cells compared with control cultures, while PTH was without significant effect. This result supports the view that PTH does not increase bone resorption in intact bone through a direct effect on osteoclasts. PGE1, which stimulates bone resorption when added to intact bone, paradoxically reduced resorption in our cultures. It thus appears possible that PGE1 acts as a direct inhibitor of osteoclastic bone resorption but has an additional effect on other cells in bone, which are induced by PGE1 to cause osteoclastic stimulation.

Alprostadil↗

Human fetal osteoclasts fail to express macrophage antigens.

A method for the isolation of osteoclasts from human fetal long bones in sufficient numbers for phenotypic studies has been devised. Using this technique we have studied the expression of cell surface antigens characteristic of mononuclear phagocytes and other haemopoietic cell types on fetal osteoclasts and compared their phenotype with mononuclear cells in the same preparations. We found that osteoclasts failed to express DrW(Ia) and 24 of 26 antigens (in 6 of 7 antigenic clusters) found on mononuclear phagocytes of the same developmental stage. This implies that osteoclasts represent the maturational end-stage of a cell lineage separate from that of conventional blood cells, and of mononuclear phagocytes in particular.

Antibodies, Monoclonal↗

Monoclonal antibodies to osteoclastomas (giant cell bone tumors): definition of osteoclast-specific cellular antigens.

The cellular origin of the osteoclast, the major agent of bone resorption, remains controversial despite the demonstration that osteoclasts form by fusion of mononuclear cells that are ultimately derived from a bone marrow stem cell. One view is that they are the terminally differentiated progeny of mononuclear phagocytic cells. However, we have previously provided evidence, from functional and phenotypic studies of rodent and human osteoclasts, that raises the possibility that osteoclasts form a separate cell lineage from conventional hemopoietic cells and macrophages in particular. In an attempt to elucidate this question, we have used monoclonal antibody techniques to examine the relationship between osteoclasts and other bone marrow-derived cells. By using osteoclasts from osteoclastomas (giant cell tumors of bone) for immunizations, we have produced 11 mouse hybridomas secreting monoclonal antibodies reacting with osteoclasts in normal human fetal bone and a variety of neoplastic and non-neoplastic bone lesions. Eight antibodies in 4 reactivity sets have been shown to recognize membrane antigens, whereas a further 3 react with cytoplasmic determinants. In 7 there is no cross-reactivity with macrophages in a wide range of tissues, thus effectively differentiating between these two cell types. These antibodies will prove useful for the identification of osteoclasts in tissues and in the separation of their circulating precursors, thus allowing an experimental approach to be made to many of the outstanding questions regarding the developmental pathobiology of the osteoclast.

Antibodies, Monoclonal↗

Cell surface characterization of the human osteoclast: phenotypic relationship to other bone marrow-derived cell types.

Among the differentiated progeny of stem cells transplantable by bone marrow are osteoclasts, the multinucleate cells which are the major agents of bone resorption. Although the osteoclast is well characterized from a structural and functional standpoint, its development and origin are still far from clear. We have used monoclonal antibodies to investigate the interrelationship between osteoclasts and other haemopoietic cells in man. We have analysed the distribution of 19 granulocyte-monocyte antigens in eight reactivity clusters on the non-neoplastic osteoclasts present within nine osteoclastomas (syn. giant cell tumours of bone) and a single example of aneurysmal bone cyst. We found that osteoclasts are antigenically effete, failing to express granulocyte-monocyte, common leucocyte or other haemopoietic determinants; the only monocyte antigens detected on osteoclasts are My-7 and two closely related specificities, MCS.2 and DüHL60.4, which are also expressed by tissues outside the haemopoietic system. Our findings, taken together with recent transplantation studies, cast further doubt on the view that osteoclasts are specialized bone-resorbing macrophage-derived giant cells, and support a hypothesis that they are the end product of fusion of a hitherto unidentified circulating mononuclear cell type, the preosteoclast, which constitutes a cell lineage separate from those originating from the conventional multipotential haemopoietic stem cell, although still of bone marrow origin.

Antibodies, Monoclonal↗

Bone abscess due to Mycobacterium xenopi.

Destructive infection of a cuneiform bone due to M. xenopi is described. The organism was isolated and its significance established by a strong skin reaction to xenopi antigen and by demonstration of bacilli in the lesion with fluorescence microscopy. This evidence of metastatic disease suggests that an alimentary route of infection as an alternative to inhalation could be considered.

Abscess↗