Biomedical subjects
Publications and source records attributed to David Moon.
Dr David Moon, head of procurement for the Waste & Resources Action Programme (WRAP), outlines how materials with higher recycled content can be economically sustainable, technically viable and easily available for construction projects in the healthcare sector.
Antiglycolipid antibodies cause a distinctive form of dysmyelination in vivo characterized by marked widening of the myelin period. Such "expanded" or "wide-spaced" myelin occurs in peripheral nerves in certain paraproteinemias and in the CNS in multiple sclerosis. We have used an in vitro system to reproduce this pathology under controlled conditions to assess the role of antibody specificity and class and the need for cofactors in generating this kind of lesion in peripheral myelin. Schwann cell myelin formed in vitro around dorsal root ganglion cell axons was exposed for 3-14 days to hybridoma cells that produce specific monoclonal antibodies. Typical wide-spaced myelin developed after exposure to either O4, which produces an IgM antisulfatide antibody, or O1, which produces an IgM antigalactocerebroside antibody. In both cases, the effect was apparent by three days in paranodal as well as internodal myelin, especially in the outer lamellae. This change did not depend on the presence of complement or macrophages in the cultures. Exposure to anti-GalC hybridoma cells, which produce an IgG3 antiglycolipid antibody, did not produce wide-spaced myelin, nor did exposure to hybridoma cells that secrete IgM antibodies directed against a non-myelin antigen. The location and rapidity of the pathologic changes seen after O4 or O1 are consistent with penetration of the antibodies through the external mesaxon of already formed myelin and then between compact lamellae, progressively spreading them apart in the centripetal direction. This in vitro model shows that either of two specific monoclonal IgM antiglycolipid antibodies can alone reproduce a well known form of myelin pathology under defined conditions.
Glial cells from neonatal MbetaP5 transgenic mice, which express bacterial beta-galactosidase (lacZ) under control of the myelin basic protein (MBP) promoter (Gow et al, 1992), were transplanted into the spinal cord or cerebral hemisphere of immunosuppressed normal and myelin-deficient (md) rats in order to assess the ability of the donor cells to survive, migrate, and differentiate within normal compared with myelin-deficient central nervous system (CNS). LacZ+ cells were detected as early as 6-7 days after transplantation into the low thoracic cord and by 10 days had spread rostrally to the brainstem and caudally to the sacral spinal cord. Initially, compact lacZ+ cells, lacking processes, were found associated with small blood vessels and with the glia limitans. Cells of this type persisted throughout the experiment. Later, lacZ+ cells with processes were seen along fiber tracts in the dorsal columns and, after intracerebral injection, subjacent to ventricular ependyma, as well as scattered in cerebral white and gray parenchyma. The extent of spread was comparable in md and normal rats, but in the md group, the success rate was higher, and more cells differentiated into process-bearing oligodendrocytes. Acceptance of xenografts in immunosuppressed recipients equaled that of allografts. The overall spread of grafted cells exceeded that of injected charcoal, indicating active migration. In contrast to earlier studies that identified oligodendrocytes based on morphology alone, this study has allowed us to identify and track oligodendrocytes based on myelin gene expression. We show some oligodendrocytes whose morphology is consistent with classical morphological descriptions, some that resemble astrocytes, and a class of compact perivascular oligodendrocyte-lineage cells that we suggest are migratory.