Biomedical subjects

M D Noble

Publications and source records attributed to M D Noble.

23 records · Page 2Linked to original sources

PubMed1981

Rat neural antigen-2 (RAN-2): a cell surface antigen on astrocytes, ependymal cells, Müller cells and lepto-meninges defined by a monoclonal antibody.

We have immunized mice with enriched populations of cultured rat astrocytes and fused their spleen cells with NS-1 myeloma cells to generate antibody-secreting hybridomas. We have isolated two stable hybridoma clones which secrete monoclonal IgG2 antibodies that react with the surface of the great majority of rat astrocytes in culture. We have studied one of these antibodies in indirect immunofluorescence assays and show that it binds to the surface of rat ependymal cells, retinal Müller cells and leptomeningeal cells as well as to astrocytes, but not to cultured neurones, oligodendrocytes, Schwann cells, microglia or various non-neural cells. The antigen defined by this monoclonal antibody is protease-sensitive and rat-specific and we have called it rat neural antigen-2 (Ran-2). We also show that isolated rat ependymal cells and cultured rat Müller cells do not express other neural cell-type-specific markers, such as tetanus toxin receptors, rat neural antigen-1 (Ran-1), galactocerebroside or glial fibrillary acidic protein (GFAP). Nor do these cells express cell surface Fc receptors for IgG, phagocytose latex beads or make detectable amounts of the Thy-1 or fibronectin glycoproteins.

Animals↗

PubMed1979

Direct effects of neostigmine on aneural myotube cultures.

Long term (24--96 h) treatment of a mouse-derived myogenic cell line (G8) with meostigmine or physostigmine markedly reduces binding of alpha-bungarotoxin (alpha-BuTx) to these cells. Protein synthesis in these cultures is markedly reduced and cell morphology degenerates. Myotubes maintain slightly hyperpolarised resting membrane potentials, and are able to respond to iontophoretic acetylcholine (ACh) application with overshooting action potentials. Prolonged exposure to neostigmine also inhibits protein synthesis in a fibroblastic cell line (B82). The results suggest that degenerative changes at the neuromuscular junction associated with chronic neostigmine treatment in vivo are due to a direct action of the anticholinesterase on the muscle, rather than to altered intracleft ACh levels [2] or to presynaptic effects of the anticholinesterase [15].

Animals↗

PubMed1978

Regulation of acetylcholine receptor levels by a cholinergic agonist in mouse muscle cell cultures.

The effects of continuous exposure to carbamylcholine (CbCho) on regulation and stabilization of acetylcholine receptors (AcChoR) were studied in cell cultures of G8, a continuous mouse muscle cell line. Exposure of cultures to 10-100 muM CbCho for 24-48 hr produced a 30-50% reduction in (125)I-labeled alpha-bungarotoxin binding. CbCho was not found to alter cell morphology, protein metabolism, or amino acid incorporation. Electrophysiological experiments demonstrated a 75% reduction in the maximum sensitivity of the myotubes to iontophoretic application of acetylcholine (AcCho). The reduction in AcCho sensitivity appeared to represent a true loss of functional receptors because there were no changes in the passive electrical properties of the cells or in the AcCho reversal potential and because receptor desensitization appeared not to be involved. Tetrodotoxin had no effect on receptor levels, either alone or in combination with CbCho. Receptor degradation in control cells could be described kinetically as a first-order process with a half-time of 19.2 hr; turnover rate in receptors remaining after prolonged exposure to CbCho was indistinguishable from that in control cells. We conclude that a receptor-active ligand can exert negative control over AcChoR levels and that prolonged exposure to an AcCho analog is not sufficient to induce a stable population of receptors in these cells.

Acetylcholine↗

PubMedDate not supplied

Prednisone-neostigmine interactions at cholinergic junctions.

The effect of corticosteroid (prednisone) and/or chronic anticholinesterase (neostigmine) treatment on alpha-bungarotoxin binding was examined in the diaphragms of male rats. In endplate regions of the diaphragm, prednisone treatment had no effect on the density of toxin binding sites, either when given alone or when administered in conjunction with neostigmine while neostigmine was observed to reduce specific binding to less than half after one week.

Animals↗

PubMedDate not supplied

Antigenic expression by cells derived from human gliomas does not correlate with morphological classification.

We have found that cell populations derived from human gliomas can be divided into antigenic classes which are not predictable on the basis of standard morphological analysis and which, most frequently, do not support the lineage assignations of various tumours as determined by traditional neuropathological methods. For example, only 6/60 cultures derived from astrocytomas expressed glial fibrillary acidic protein (GFAP), an astrocyte specific marker, and all six of these cultures were derived from morphological categories which more frequently gave rise to populations which did not express GFAP. None of the seven oligodendrogliomas or four oligo-astrocytomas examined expressed antigens specifically expressed by oligodendrocytes. Most tumour-derived populations, from all classes of tumour and all grades of malignancy, expressed cell-surface fibronectin, an extracellular matrix protein only rarely found on the surfaces of CNS macroglia; such cells did not express glial-specific antigens (e.g., GFAP) in vitro. Investigation of antigen expression in tumour biopsies indicated that some tumours also consisted largely or wholly of cells which expressed fibronectin in situ. Fibronectin-expressing cells were aneuploid and were not contact inhibited in their growth, indicating that they were transformed cells. We have also identified two previously unknown antigenic phenotypes among the gliomas.

Antigens, Neoplasm↗