Harry Bartfeld

Ganglioside Induced Surface Activity and Neurite Formation of Neuro-2A Neuroblastoma Cells

These studies demonstrate that while microtubules are essential for BBG-mediated neurite initiation and elongation, they are not involved in microfilament-dependent ganglioside-mediated surface activity. Microfilaments may be more directly altered by exogenous gangliosides than microtubules since they are the major structural elements of microvilli and are required for neurite branching. Our studies suggest that normal neuritogenesis requires a delicately balanced interaction between various cytoskeletal elements. Since there is a close relationship between membrane-associated lipid molecules and submembranous cytoskeletal elements, the incorporation of gangliosides into membranes may alter this balance and result in neurite formation. The use of gangliosides to enhance neurite production provides a unique model for the study of nerve development. We have shown that bovine brain gangliosides stimulate an immediate sequence of surface-related changes as well as microtubule and microfilament dependent neurite formation in Neuro-2a cells. However, the precise molecular events by which gangliosides enhance neuritogenesis await further study.

Cytophilic nature of migration inhibitory factor associated with delayed hypersensitivity.

Summary Macrophage migration inhibition tests of delayed sensitivity showed that trypsinization of sensitive peripheral blood lymphocytes did not affect their mediating ability or production of migration inhibitory factor (MIF). Trypsinization of normal macrophages abolished their response to sensitive lymphocytes or MIF; their ability to respond was recovered when first cultured for 20 hr but not 4 hr. The MIF was absorbed to a greater degree by untreated than by trypsinized macrophages. These findings suggest the presence of macrophage receptors for MIF and the cytophilic nature of the latter.

Immunoregulatory and activated T cells in amyotrophic lateral sclerosis patients

Circulatory immune complexes are increased in amyotrophic lateral sclerosis (ALS) and an autoimmune mechanism has been inferred. Autoimmune diseases may have changes in the percentages of immunoregulatory T cells and increased activated T cells (Ia+ T) in peripheral blood. The latter are also increased with active viral and bacterial infection and immunization. We found no significant changes of the percentages of immunoregulatory T cells and no relation of the individual values to the clinical state. Ia+ T cells were not increased over the normal range but within that range there was significant negative correlation with the ALS clinical score.

Kinetics of Replication of Lactate Dehydrogenase-Elevating Virus in Age-Dependent Polioencephalomyelitis

The kinetics of replication of lactate dehydrogenase-elevating virus (LDV) in age-dependent polioencephalomyelitis was studied in genetically susceptible (C58/J) and resistant (C57BL/6J) mice. The peripheral replication pattern (plasma concentration) for LDV was similar in both strains. However, the concentration of virus within the central nervous system was strikingly different. In nonsusceptible C57BL/6J mice, little or no virus was found within the central nervous system. In the lumbar cord of susceptible C58/J mice, an increase in the concentration of LDV began 5 days postinfection and continued during the preclinical stages of disease. A direct correlation was shown between the concentration of LDV in spinal cord and the appearance of motor neuron disease but not the degree of inflammatory reaction.

Enteroviral-Related Antigen in Circulating Immune Complexes of Amyotrophic Lateral Sclerosis Patients

Circulating immune complexes were isolated by polyethylene glycol precipitation from the sera of patients with amyotrophic lateral sclerosis. Rabbits immunized with circulating immune complexes from 3 of 5 amyotrophic lateral sclerosis patients induced antisera that specifically reacted with enterovirus-infected cells by immunofluorescence and enzyme-linked immunosorbent assay. These antisera were nonneutralizing and did not react with purified virus. In addition, peripheral lymphocytes of amyotrophic lateral sclerosis patients produced lymphokine in response to extracts from enterovirus (Coxsackie B4) infected cells. These results suggest both a humoral (circulating immune complex) and a cellular immune response in some patients with amyotrophic lateral sclerosis to enterovirus-coded or -induced antigen.