Biomedical subjects

D H Silberberg

Publications and source records attributed to D H Silberberg.

At least 37 records · Page 2Linked to original sources

PubMed1988

Neuroblastoma cell-oligodendrocyte interaction is mediated by neural cell adhesion molecules.

The role of neural cell adhesion molecule (NCAM) in the interaction between neurons and oligodendrocytes was studied using N2A neuroblastoma cells, which express only the 180,000 Mr NCAM and rat oligodendrocytes which express only 120,000 Mr NCAM. Oligodendrocytes bound to neuroblastoma cells, and the binding was inhibited by anti-NCAM, suggesting that NCAM is involved in oligodendrocyte-neuron interaction. The possible role of NCAM in myelination and remyelination is discussed.

Antigens, Surface↗

PubMed1988

Azathioprine in multiple sclerosis: the cons.

Azathioprine has the longest continuing history of clinical use in the treatment of multiple sclerosis (MS) of any immunosuppressive therapy besides corticosteroids. To date, 19 clinical trials of azathioprine in MS have been reported, and another eight are under way. A review of the reported trials indicates little evidence for a therapeutic effect in MS. This and the lack of evidence for a specific immune alteration in the pathogenesis of MS are relative contraindications for the use of high risk immunosuppressive therapies in this disease. A further caveat is raised by a recent report suggesting that azathioprine may have contributed to an increased incidence of carcinomas in MS patients treated with this drug. In view of these considerations, perhaps the best position to take at the present time is to encourage investigators already engaged in controlled clinical trials of azathioprine to complete their work, so that this data can be considered before new studies of azathioprine in MS are undertaken.

Azathioprine↗

PubMed1987

C6 glioma cells express modified neural-cell adhesion molecule-like glycoproteins.

We have studied the expression of neural-cell adhesion molecule (N-CAM)-like glycoproteins in a C6 glioma cell line. We found that: (a) C6 cells express N-CAM-like proteins on the cell surface, (b) the N-CAM-like proteins in C6 cells have apparent molecular weights of 130,000 and 150,000 kDa which are not seen in rodent brain and (c) deglycosylation of C6 N-CAMs suggest that the modifications are both in the carbohydrate and protein parts of the N-CAM. The expression of modified N-CAM glycoproteins is of interest in relation to the regulation of N-CAM expression.

Animals↗

PubMed1987

Multiple sclerosis disease activity correlates with gadolinium-enhanced magnetic resonance imaging.

Magnetic resonance imaging provides a method of visualizing multiple sclerosis plaques, but the age and activity of these plaques cannot be determined with routine magnetic resonance images. Gadolinium DTPA is a paramagnetic contrast agent that does not cross an intact blood-brain barrier. We studied 16 patients with multiple sclerosis, using magnetic resonance imaging, gadolinium-enhanced magnetic resonance imaging, and computed tomographic scans. Gadolinium enhancement of multiple sclerosis plaques correlated with the clinical activity of the disease and corresponded anatomically with the symptoms and signs. We conclude that gadolinium enhancement of magnetic resonance images is a promising tool in the investigation of multiple sclerosis lesions and that it may provide a method for objective follow-up in clinical trails.

Adult↗

PubMed1987

Search for antibodies to galactocerebroside in the serum and cerebrospinal fluid in human demyelinating disorders.

To determine if galactocerebroside (GalC) is a target antigen in the human demyelinating disorders multiple sclerosis, Guillain-Barré syndrome, and chronic demyelinating inflammatory polyneuropathy, we examined the serum and cerebrospinal fluid from patients with these disorders and from control subjects using four assay systems. In none of these assays could we detect significant differences in anti-GalC antibody titer between patients with demyelinating diseases and normal subjects or patients with other neurological disorders. Our data suggest that there is no humoral immune response to GalC in human demyelinating disorders.

Antibodies↗

PubMed1987

Expression of MHC class I genes in mouse hepatitis virus (MHV-A59) infection and in multiple sclerosis.

Our studies revealed that virus induced demyelination as well as human inflammatory demyelination involves upregulation of class I MHC genes and surface expression of antigens encoded by these genes. Induction involves the action of an intermediate soluble factor/s which is at present unknown. These findings suggest that MHC class I restricted, cytotoxic T lymphocyte (CTL) reactions, against self or foreign antigens may play a role in these conditions. These findings may help to elucidate the mechanism of coronavirus-induced demyelination as well as the pathogenesis of multiple sclerosis.

Animals↗

PubMed1987

Coronavirus mouse hepatitis virus (MHV)-A59 causes a persistent, productive infection in primary glial cell cultures.

MHV-A59 causes a chronic demyelinating disease in mice which is accompanied by persistence of viral genome in white matter. As part of the investigation into the mechanism of viral persistence, infection of glial cells, probable targets for chronic infection, was studied by the use of mixed glial, enriched oligodendrocyte and enriched astrocyte cultures. Following MHV-A59 infection in vitro, approximately 10% of oligodendrocytes and 30% of astrocytes expressed viral antigens in the absence of overt cytopathic effect. All cultures released infectious virus for the lifetime of the cultures, for at least 45 days in the case of mixed glial cultures. Cultures derived from previously infected mice were similar to those infected in vitro with respect to percentage of cells expressing viral antigen and levels of infectious virus produced. These results show (1) that glial cells are early sites of infection in vivo as well as sites of infection in vitro cultures, and (2) that glial cells support a non-lytic but productive infection in vitro and thus may contribute to viral persistence in vivo.

Animals↗

PubMed1986

Coronavirus infection induces H-2 antigen expression on oligodendrocytes and astrocytes.

Infection of the central nervous system by mouse hepatitis virus strain A59, a murine neurotropic coronavirus, induces class I major histocompatibility complex antigens on mouse oligodendrocytes and astrocytes, cells that do not normally express these antigens on their surfaces. This induction, which occurs through soluble factors elaborated by infected glial cells, potentially allows immunocytes to interact with the glial cells and may play a critical role in the pathogenesis of virus-induced, immune-mediated demyelination in the central nervous system.

Animals↗

PubMed1986

Remyelination follows antibody-induced central nervous system demyelination.

Remyelination after anti-galactocerebroside-induced demyelination in the guinea pig optic nerve was evident 17 days after the onset of demyelination. The tempo of remyelination was uniform for large- and small-diameter axons and progressed, with compaction and thickening of myelin sheaths. Demyelinated axons were found interspersed among remyelinated fibers and were consistently separated from oligodendrocytes by astrocytic processes. These findings indicate that central nervous system remyelination may occur after in vivo antibody-induced demyelination, but that new myelin formation may be limited by mechanical interference from astrocytic processes.

Animals↗

PubMed1986

The expression of MHC antigens on oligodendrocytes: induction of polymorphic H-2 expression by lymphokines.

Neither class I nor class II major histocompatibility complex (MHC) antigen has been demonstrated in native oligodendrocytes, the possible target of viral or immune damage in multiple sclerosis (MS). In this report, we show that H-2, but not Ia, antigen expression is induced on isolated mouse oligodendrocytes in vitro by crude supernatant from lectin-activated spleen cells, lectin-free interleukin 2, and cloned gamma-interferon. This induction of H-2 expression is not accompanied by proliferation of oligodendrocytes, whereas MHC induction in spleen cells is highly related to their proliferation, or blastoid transformation. Oligodendrocytes as well as other brain cells are probably isolated from these lymphokines by the blood-brain barrier (BBB). However, it is possible that oligodendrocytes express MHC class I antigen as a consequence of impairment of the BBB, or in the presence of activated T-cells which have been demonstrated in active MS lesions. This activation then renders oligodendrocytes possible target cells for MHC-restricted cytotoxic T-cells.

Animals↗

PubMed1986

Serum cytotoxicity to oligodendrocytes in multiple sclerosis and controls: assessment by 51Cr release assay.

In order to quantitate oligodendrocyte cytotoxicity induced by sera from patients with multiple sclerosis (MS) and control sera, we established a 51Cr release assay system using cultured oligodendrocytes as target cells. With this assay system, we detected serum-induced cytotoxicity in isolated oligodendrocytes in sera from patients with MS, other neurological diseases (OND) and normal individuals. Oligodendrocytes were much more susceptible than astrocytes. The serum cytotoxicity was abolished by heating sera at either 56 degrees C or 50 degrees C for 30 min, and disappeared in storage at 23 degrees C for 1 month or at 4 degrees C for 2 months. Addition of fresh guinea pig serum as a source of complement did not restore the cytotoxic effect. Although the serum factor cytotoxic to oligodendrocytes is not specific for sera from patients with MS, it is possible that it may damage oligodendrocytes if the blood-brain barrier is impaired, as occurs in MS.

Animals↗

PubMed1986

A monoclonal antibody raised to corpus callosum extract reacts with 2',3'-cyclic nucleotide 3'-phosphohydrolase.

Monoclonal antibody against 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) was generated by fusing mouse myeloma cells with spleen cells from BALB/c mice immunized with delipidated white matter from rat corpus callosum. The antibody was characterized by solid-phase radioimmunoassay, immunoblot of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), immunoprecipitation from C6 glioma cells, and indirect immunofluorescence staining of monolayer cultures containing oligodendrocytes. The monoclonal antibody bound specifically to an intracellular antigen of oligodendrocytes, but not to Schwann cells, astrocytes, neurons, or fibroblast cytoplasm. The immunoblot of SDS-PAGE of CNS myelin showed that the antibody identified two protein bands at 48,000 and 50,000 molecular weight. These proteins were not identified in peripheral nervous system myelin. The monoclonal antibody immunoprecipitated CNP enzyme activity from extracts of C6 glioma cells. This monoclonal antibody should prove useful in further study of this myelin-specific enzyme in CNS myelin and in cells responsible for myelin production.

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase↗

PubMed1986

Multiple sclerosis: gadolinium enhancement in MR imaging.

Magnetic resonance (MR) images--both nonenhanced and enhanced with gadolinium DTPA/dimeglumine (Gd)--were compared with high-iodine (88.1 g I) computed tomographic (HICT) scans in demonstrating lesions in 15 patients known to have multiple sclerosis (MS). T1-weighted, mixed (T1, proton density, and T2), and T2-weighted MR pulse sequences were used. More than 20 lesions in each of 14 patients were demonstrated by pre-Gd mixed images and T2WI. Nine patients had clinical symptoms of active disease. Gd-enhanced T1WI showed at least one lesion that appeared to correspond with newly reported symptoms or signs. In addition, three clinically stable patients showed enhancement. Enhancement was best seen on 3-minute T1WI. HICT scans showed enhancement in four of the nine patients with active disease and in none of five clinically stable patients. Gd-enhanced MR imaging appears to be more sensitive than HICT in the detection of the transient abnormalities of the blood-brain barrier that occur in patients with active MS and appears capable of distinguishing active lesions that may correspond to the anatomic regions responsible for abnormal clinical findings.

Adult↗

PubMed1986

Serum-mediated oligodendrocyte cytotoxicity in multiple sclerosis patients and controls.

We examined serum-mediated cytotoxicity on cultured rat oligodendrocytes, using serum from patients with acute or chronic progressive multiple sclerosis and normal controls. We found heat-labile serum factors in serum from MS and also in controls. The cytotoxic effects of MS and normal sera were not restored by adding a source of complement. Despite apparent lack of disease specificity, such factors might damage oligodendrocytes if they gained access to these cells through a damaged blood-brain barrier in MS or other disorders.

Adult↗

PubMed1986

Astrocytes, oligodendrocytes, and Schwann cells share a common antigenic determinant that cross-reacts with myelin basic protein: identification with monoclonal antibody.

We have produced a monoclonal antibody against myelin basic protein that reacts with astrocytes, oligodendrocytes, and Schwann cells. This antibody was generated by fusion of mouse myeloma cells with spleen cells from BALB/c mice immunized with delipidated white matter from adult rat corpus callosum. The antibody was characterized via solid-phase radioimmunoassay, immunoblot of SDS-PAGE, and by indirect immunofluorescence staining of monolayer cultures containing oligodendrocytes, astrocytes, and Schwann cells. Myelin basic protein (MBP) was shown previously to be present only in myelin producing cells in CNS and PNS (oligodendroglia and Schwann cells) and not in astrocytes. The binding of this monoclonal antibody to all 3 cell types suggests that these cells share a common epitope. This epitope may be related to a common progenitor cell.

Animals↗

PubMed1986

Oligodendrocyte cell adhesion molecules are related to neural cell adhesion molecule (N-CAM).

The glycoproteins responsible for calcium-dependent oligodendrocyte aggregation were purified and characterized. Using detergent extraction, lentil-lectin-Sepharose 4B affinity chromatography, and preparative gel electrophoresis, 3 proteins were purified to apparent homogeneity, with relative Mrs of 120,000, 140,000, and 180,000. The aggregation assay showed that all 3 proteins had the ability to block antibody-mediated inhibition of oligodendrocyte aggregation. The 120,000 protein was the most active of the three. Antisera were raised in rabbits to these 3 individual proteins. Western blot analyses showed that all three antisera recognized 120,000, 140,000, and 180,000 proteins, which indicated that the proteins were related. Western-blot analyses of cultured oligodendrocytes and purified rat myelin showed only the 120,000 protein. Immunoprecipitation of iodinated membrane proteins of cultured oligodendrocytes also indicated the presence of only the 120,000 Mr protein. Deglycosylation of the 120,000 protein by N-glycanase resulted in a 110,000 protein. The immunoblot pattern suggested some similarities between oligodendrocyte adhesion molecules and the neural cell adhesion molecule (N-CAM). Therefore, the 120,000, 140,000, and 180,000 Mr proteins were compared to N-CAM by Western-blot analysis, immunofluorescence staining, and by immunoprecipitation. The results suggest that oligodendrocytes contain a 120,000 membrane glycoprotein that is related to N-CAM.

Animals↗

PubMed1985

Expression of H-2 antigen on oligodendrocytes is induced by soluble factors from concanavalin A activated T cells.

It has been shown that soluble factors from activated T cells, or interferon alone, enhance the expression of major histocompatibility complex (MHC) antigens in several cell types. In this study we have demonstrated, by means of indirect immunofluorescence and radioimmunoassay, that the expression of mouse MHC class I antigen (H-2) on isolated mouse oligodendrocytes is induced by soluble factors from concanavalin A activated T cells. Autoradiographic studies indicate that this induction of H-2 expression is not accompanied by proliferation of oligodendrocytes.

Animals↗

PubMed1985

Fibroblast growth factor is a mitogen for oligodendrocytes in vitro.

The effect of fibroblast growth factor (FGF) on oligodendrocyte development has been studied using dissociated mixed brain cells, cultured in a previously described serum-free medium. A greater number of galactocerebroside-positive oligodendrocytes could be demonstrated after 7 days in the presence of FGF than in control values. Using combined immunofluorescence and autoradiography an increased [3H]thymidine incorporation by galactocerebroside-positive oligodendrocytes was demonstrated after various times of exposure to FGF.

Animals↗