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A Zurbriggen

Publications and source records attributed to A Zurbriggen.

106 records · Page 6Linked to original sources
PubMed1987

Demyelinating, non-demyelinating and attenuated canine distemper virus strains induce oligodendroglial cytolysis in vitro.

A virulent canine distemper virus (CDV) strain that causes demyelination in vivo has been shown to induce oligodendroglial degeneration in vitro. In order to investigate if this effect on oligodendrocytes is specific for demyelinating strains only, primary brain cell cultures were infected with either virulent demyelinating strains (A75/17 and CH84-CDV), a virulent non-demyelinating strain (SH-CDV) or a non-virulent strain (OP-CDV). All virulent viruses caused a persistent type infection with moderate cytolysis whereas the non-virulent strain was highly cytolytic. All strains induced a similar pattern of oligodendroglial degeneration. It was concluded that the ability to induce oligodendroglial degeneration, which is thought to be the in vitro correlate of demyelination in vivo, is inherent to CDV irrespective of the strain. The discrepancy between biological behaviour of CDV strains in brain cell cultures and in vivo can be explained by the more complex virus-cell interactions in vivo than in vitro.

Animals↗
PubMed1986

Canine distemper virus clearance in chronic inflammatory demyelination.

The distribution of canine distemper virus (CDV) antigen was examined in the brains of 14 dogs with chronic nervous distemper using a monoclonal antibody against a major viral protein. In ten of these dogs, neutralizing anti-CDV antibody titers were determined in serum and unconcentrated cerebrospinal fluid (CSF). In 19% of the inflammatory demyelinating lesions, large amounts of CDV antigen were found; in 34% of these lesions only residual traces of virus were seen and in almost half of the lesions (47%) no CDV could be demonstrated. In four dogs neutralizing antibodies were found in the serum only; in one dog in the CSF only and in 5 dogs both in serum and CSF. Because of the correlation between the presence of inflammation, intrathecal antiviral antibodies and disappearance of CDV from the lesions, it was concluded that the inflammatory response in distemper is associated with viral clearance from the lesions. Associated immune-mediated cytotoxic reactions could explain exacerbation of the initial virus-induced demyelinating lesions. Despite the presence of an apparently effective intrathecal antiviral immune response, fresh non-inflammatory lesions as a result of viral replication and spread in the white matter coexisted with inflammatory ones in which viral clearance had taken place. The role and mechanism of such virus persistence are discussed.

Animals↗
PubMed1986

Studies on the intrathecal humoral immune response in canine distemper encephalitis.

Albumin and IgG were quantitated in paired cerebrospinal fluid (CSF) and serum samples from dogs with demyelinating canine distemper virus (CDV) infection by means of rocket immunoelectrophoresis. The IgG index as indicator for intrathecal immunoglobulin synthesis was normal in animals with non-inflammatory demyelinating lesions and elevated in dogs with inflammatory myelin lesions. Specific antibodies against CDV and myelin were quantitated in CSF and serum from 8 dogs with an elevated IgG index. Eight of these dogs had significant amounts of antimyelin antibody and 4 dogs had neutralizing anti-CDV antibody in the CSF. Whereas the pathogenetic significance of antimyelin antibodies remains uncertain, the intrathecal antiviral immune response provides a plausible explanation for immunopathologic destruction of myelin in distemper.

Albumins↗
PubMed1986

Secondary degeneration of oligodendrocytes in canine distemper virus infection in vitro.

To study the pathogenesis of demyelination in canine distemper virus (CDV) infection, primary canine brain cell cultures were infected with CDV to examine specific virus-induced glial cell changes. Cultures were harvested at regular intervals after inoculation and were immunostained for the specific demonstration of astrocytes, oligodendrocytes, and CDV antigen. The infection spread slowly with moderate cytolysis and cell fusion. Soon after inoculation, infection of astrocytes was found by means of double immunofluorescent labeling. One week after inoculation, CDV-induced astrocytic fusion and rearrangement of astroglial fibrils became apparent. The astrocytic changes progressed during the observation period. Double immunofluorescent labeling failed to show oligodendroglial infection. Despite clear absence of viral replication within oligodendrocytes at all stages of the experiment, these cells exhibited marked pathologic changes starting at about 20 days after inoculation and progressed to complete cytolysis within 10 days. The degeneration of the oligodendrocytes was thought to be secondary to CDV-induced changes in other cell types of the culture probably through the release of toxic factors in the tissue culture medium. Since little evidence has been found for oligodendroglial infection in demyelinating lesions in canine distemper in vivo, the present tissue culture findings suggest that demyelination in vivo could be the result of indirect oligodendroglial damage caused by CDV-induced changes in other cell types such as astrocytes.

Animals↗
PubMed1985

Spread and distribution of viral antigen in nervous canine distemper.

Canine distemper virus (CDV) antigen was demonstrated immunocytochemically in the central nervous system (CNS) of 19 dogs killed from 16 to 170 days after infection. In the earliest lesions, infection of glial cells preceded demyelination, and the degree of myelin destruction correlated with the amount of viral antigen in the tissue. It was concluded that initial demyelination in distemper is directly viral-induced, but the nature of the infected glial cells remains uncertain. Ependymal infection and spread of virus in the subependymal white matter was often seen, suggesting invasion of CDV into the CNS along the CSF pathways. Inflammation during the latter stages of the infection appeared to be associated with viral clearance from the CNS in most dogs. In two dogs with chronic progressive neurologic distemper, viral antigen was still present in the brain suggesting that viral persistence and associated immunologic reactions may contribute to further myelin damage. With the exception of one dog that survived for 6 months after infection, viral antigen was no longer detected in the dogs that had recovered.

Animals↗
PubMed1985

Canine distemper virus does not infect oligodendrocytes in vitro.

Dissociated canine brain cell cultures were infected with virulent canine distemper virus (CDV). Double immunofluorescent labelling was done to simultaneously demonstrate viral antigen and specific glial cell markers. Virus containing oligodendrocytes were not found at any stage of the infection. A certain proportion of the infected cells were shown to be astrocytes. It was concluded that CDV has no obvious tropism for oligodendrocytes which could explain the mechanism of demyelination in distemper in vivo.

Animals↗
PubMed1985

A monoclonal antibody that binds to both astrocytes and myelin sheaths.

A monoclonal antibody designated III 5H8 was shown to bind both to astrocytes and to myelin sheaths as studied with immunocytochemical techniques on brain sections and cell cultures. Binding to astrocytes was confirmed by double immunofluorescent labelling of frozen sections and cell cultures with anti-GFAP, and appeared to be sensitive to formalin treatment. Binding to myelin sheaths was confirmed by comparing sections labelled with III 5H8 with sections labelled with antibodies against axons and myelin basic protein as well as by staining of sections of hypomyelinated spinal cord with III 5H8. On immunoblots of separated white matter III 5H8 revealed two bands, while on immunoblots of purified myelin only one band was seen. The findings are discussed with respect to the function of astrocytes in white matter and shared antigenic determinants between astrocytes and oligodendrocytes.

Animals↗
PubMed1984

Demyelinating polyneuropathy associated with monoclonal IgM-paraproteinaemia. Histological, ultrastructural and immunocytochemical studies.

Histological, ultrastructural and immunocytochemical findings of sural nerve biopsies from 2 patients with monoclonal IgM-paraproteinaemia are presented. In both cases the pathological IgM antibodies reacted with a myelin antigen which was identified as myelin-associated glycoprotein (MAG) by immunoelectroblot . Histology and electron microscopy showed typical features of a chronic demyelinating neuropathy with accompanying axonal degeneration. Immunohistochemical studies demonstrated IgM in the vicinity of endoneurial vessels and on some of the myelinated fibres. The localisation of IgM on the myelin sheath showed a typical pattern, which was similar to that found in binding studies with the patients sera on control nerves. It resembled the characteristic immunocytochemical staining pattern of MAG. Binding studies with the patients' sera on human and canine CNS material exhibited a clear labelling of white matter and certain, as yet unidentified structures within the cerebral and cerebellar cortex. In mixed glial cell cultures, the sera of both patients bound specifically to oligodendrocytes. Our observations are interpreted as immunohistochemical evidence that the anti-MAG antibodies of the patients' sera had bound to their antigenic target in the peripheral nerves. Because the antibodies clearly react to central myelin, oligodendrocytes and other not yet identified cortical structures, CNS involvement in such disorders should be considered.

Aged↗
PubMed1984

Myelin-associated glycoprotein is produced before myelin basic protein in cultured oligodendrocytes.

Mixed glial cell cultures from neonatal dog cerebellum were harvested daily between 3 and 21 days after seeding and studied with immunocytochemical techniques for the demonstration of myelin-associated glycoprotein (MAG) and myelin basic protein (MBP). Both MAG and MBP were detected in the cultures and by means of double labelling techniques shown to be produced by the same cells. MAG+ cells occurred earlier and were always more numerous than MBP+ cells. These results suggest that the oligodendrocyte in vitro expresses MAG before MBP. The findings are discussed in respect to oligodendroglial differentiation and myelination in vivo.

Animals↗
PubMed1984

Morphological and immunocytochemical characterisation of mixed glial cell cultures derived from neonatal canine brain.

Three different regions from neonatal dog brain were mechanically dissociated and cultured. At seven, 10, 14 and 19 days, cultures were harvested and studied with immunocytochemical techniques for the demonstration of astrocytes, oligodendrocytes and fibroblasts. The canine brain cultures were confluent at seven days and contained fibroblasts, both types of glial cells and several small fragments of undissociated brain tissue. Many cells were myelin associated glycoprotein (MAG) positive. In the older cultures increasing numbers of myelin basic protein (MBP) positive oligodendrocytes were also demonstrated. Double labelling studies demonstrated that MBP and MAG were produced by the same cells. MAG positive cells were therefore identified as oligodendrocytes. Most intensive oligodendroglial growth occurred in the vicinity of undissociated tissue fragments. The results were discussed in respect to glial differentiation and the question of whether the canine cultures may contain neurons.

Animals↗
PubMed1983

Canine distemper virus-induced glial cell changes in vitro.

In vitro studies on glial cell changes in canine distemper virus (CDV) infection could be useful for the understanding of the pathogenesis of demyelination in vivo in this disease. Mixed glial cell cultures derived from neonatal mice and dogs were infected with CDV and examined using immunocytochemical techniques demonstrating specific oligodendroglial and astroglial cell markers. Astrocytic changes were similar in both murine and canine cultures and consisted of loss of processes, cell fusion, and cell necrosis. Marked oligodendroglial lesions were apparent in the canine brain cultures and were characterized by focal perikaryal protrusions, swelling and loss of cell processes, and cell necrosis. Fusion between oligodendrocytes was not observed. Fusion between astrocytes and oligodendrocytes could not be documented with double labeling techniques. In contrast to the canine cultures, murine oligodendrocytes remained relatively unaffected by the infection. These findings were discussed with respect to cell pathology and mechanisms of demyelination in vivo. The exact nature of the canine oligodendroglial lesions in vitro needs to be studied in further experiments.

Animals↗
PubMed1983

Human monoclonal antibodies to myelin-associated glycoprotein. Comparison of specificity and use for immunocytochemical localisation of the antigen.

Recent reports demonstrate that a population of patients with gammopathy and demyelinating neuropathy have monoclonal antibodies to myelin-associated glycoprotein. Using the immunoblotting technique we compared the species specificity: human monoclonal antibodies to myelin-associated glycoprotein reacted with human, monkey, calf, dog, rabbit and guinea pig myelin, but not with rat or mouse. On the immunoblot myelin-associated glycoprotein consistently stained as a diffuse band with an apparent molecular weight ranging from 90-100 X 10(3) dalton. Experiments showed that when human CNS myelin had been incubated at 37 degrees C before gel electrophoresis, there was a general shift of staining towards the lower end of the molecular weight range. This low molecular weight myelin-associated glycoprotein, when released from the membrane, contains the antigenic determinant. Peptide mapping by limited proteolysis reveals that the antigenic determinants for 4 different monoclonal antibodies appear to lie very close together in the molecule. The distribution of the antigen was studied in nervous tissue with the unlabelled peroxidase-antiperoxidase method. The results obtained are in close agreement with the localization reported with polyclonal antisera to myelin-associated glycoprotein.

Animals↗
PubMedDate not supplied

Immunity to viruses.

Explore the source record for details and available documents.

Antibodies, Viral↗
PubMedDate not supplied

Generation and functional characterisation of canine bone marrow-derived macrophages.

A culture of bone marrow cells from the femurs of canine pups at high concentrations of fetal calf serum under non-adherent conditions allowed the proliferation and differentiation of mononuclear phagocyte lineage cells, as evidenced by morphology and CD14 expression. Cells from other lineages progressively diminished in numbers. Cells collected between 12 and 19 days of culture expressed an array of macrophage activities including ingestion of opsonised erythrocytes, generation of superoxide, up-regulation of procoagulant activity and synthesis of tumour necrosis factor (TNF) upon appropriate stimulation. TNF production was enhanced when the cultures were simultaneously stimulated with canine recombinant, or supernatant-derived, interferon-gamma. In contrast, low levels of inducible nitric oxide (NO) synthase were expressed by only a minority of stimulated macrophages, and nitrite could not be detected in the medium. Therefore, canine macrophages generated by this novel culture system resemble human macrophages in their inefficient and restricted generation of NO upon appropriate stimulation.

Animals↗
PubMedDate not supplied

Identification of canine glial cells by nonradioactive in situ hybridization.

Studies on the development of the canine central nervous system and on demyelinating diseases demand unequivocal identification of the glial cells. For that reason, nonradioactive in situ hybridization (ISH) was performed in primary dog brain cell cultures (DBCC) and in brain sections of neonatal dogs. Specific RNA probes were used to detect messenger RNA (mRNA) coding for proteolipid protein (PLP), myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP). PLP and MBP are markers for oligodendrocytes, GFAP for astrocytes. Oligodendrocytes positive for PLP and MBP mRNA were found in both DBCC and brain sections of neonatal dogs. Astrocytes expressing GFAP specific mRNA were detected in DBCC and in brain sections. These cells were evenly distributed in the white matter with additional accumulation in the membrana limitans gliae superficialis, around the ventricles and blood vessels. ISH clearly improves the study of oligodendrocytes in brain sections as, in contrast to the immunohistochemical methods, this technique allows to identify individual cells.

Animals↗