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Biomedical subjects

H Thormar

Publications and source records attributed to H Thormar.

At least 55 records · Page 3Linked to original sources
PubMed1985

Measles virus encephalitis in ferrets as a model for subacute sclerosing panencephalitis.

Young adult ferrets were used as experimental animals to study subacute sclerosing panencephalitis (SSPE). When cells infected with cell-associated measles virus strains isolated from SSPE patients were inoculated intracerebrally (i.c.) into ferrets, they developed an acute encephalitis and died within 1 to 3 weeks without detectable antibody formation. Immunization with live measles vaccine 5 weeks before i.c. inoculation changed the course of the infection in about 50% of the ferrets. These animals developed a subacute encephalitis within weeks or months after inoculation. Cell-associated measles virus was isolated from their brains and high measles antibody titers were found in their sera, comparable to those in sera of SSPE patients. Measles virus specific immunoglobulins (IgG) were present in their brains and determination of IgG/albumin ratios indicated that antibodies were synthesized in the brain in response to the persistent measles virus infection. Measles specific oligoclonal IgG bands were found in the sera and spinal fluids of these animals. Therefore, subacute ferret encephalitis has virological and immunological characteristics in common with SSPE, indicating that it may serve as a model for the human disease. Other animal models of SSPE are described briefly.

Animals↗
PubMed1983

Pathogenesis of viral encephalitis: demonstration of viral antigen(s) in the brain endothelium.

One of the enigmas in the pathogenesis of inflammation is why the white cells adhere to the endothelium. In trying to define the pathogenic mechanism, we carried out experiments on ferrets infected with an SSPE strain of measles virus. Using immunoperoxidase labeling techniques, viral antigens were demonstrated on the luminal surface and in the cytoplasm of endothelial cells, irrespective of the presence or absence of inflammatory changes. The degree of inflammation corresponded well with antibody titer. These data suggest that the viral antigen in the endothelial cells is the site of interaction between these cells and sensitized lymphoid cells.

Animals↗
PubMed1983

The emergence of antigenic variants is a rare event in long-term visna virus infection in vivo.

Six sheep persistently infected with visna virus were studied for 4 1/2 to 5 3/4 years until they became ill. Virus was isolated at intervals from peripheral blood leukocytes and cerebrospinal fluid (CSF), and at the time of sacrifice from various parts of the brain and the lungs. Both brain and lungs showed lesions typical of advanced visna/maedi. All the sheep formed antibodies in sera and CSF. Virus isolates from each sheep were tested in neutralization tests against sera and CSF collected from the same animal. In one sheep all isolates were found to be identical to the inoculated virus by this test. In each of the other sheep an antigenic variant emerged from 1 to 3 years after inoculation and remained in circulation even after the formation of autologous antibodies. In one case a variant was isolated from the lungs, whereas in all cases the virus isolated from the brain was identical to the inoculated virus. The results show that antigenic variants are rare in visna and do not seem to have a role in the pathogenesis of the disease.

Animals↗
PubMed1983

Presence of oligoclonal immunoglobulin G bands and lack of matrix protein antibodies in cerebrospinal fluids and sera of ferrets with measles virus encephalitis.

Young adult ferrets were immunized with measles vaccine and 5 to 6 weeks later inoculated intracerebrally with Vero cells persistently infected with cell-associated strain D.R. of measles virus isolated from a patient with subacute sclerosing panencephalitis. Of nine ferrets which survived the infection for 3 weeks or longer, five showed neurological signs. At the time of death they had widespread inflammation in their brains, and cell-associated virus was isolated from three ferrets sacrificed from 5 weeks to 7 months after inoculation. Four ferrets did not develop clinical signs, but two of these had mild inflammation in the brain 7 months and 2 1/2 years after inoculation, respectively. Cerebrospinal fluids drawn by cisternal puncture from infected ferrets at the time of sacrifice had neutralizing titers against measles virus similar to the titers found in sera, but antibody against the measles virus matrix protein was not detectable. Cerebrospinal fluid showed increased immunoglobulin G (IgG) and had distinct measles virus-specific oligoclonal IgG bands. The intensity of the bands correlated with the neutralizing titers of the fluids. These results confirm and extend earlier findings and indicate that persistent measles virus infection in ferrets is similar to human subacute sclerosing panencephalitis and can be used to study certain aspects of persistent brain infections leading to subacute encephalitis.

Animals↗
PubMed1983

Visna.

Explore the source record for details and available documents.

Animals↗
PubMed1982

Subacute sclerosing panencephalitis antibodies against measles virus polypeptides.

Antibodies to measles virus proteins in SSPE, MS and control human sera were compared using measles virus strain Edmonston, productive SSPE strain Mantooth and non-productive SSPE strain DR. The viral antigens were subjected to transfer electrophoresis, incubated with sera and localized after a second incubation with peroxidase labeled immunoglobulins. High levels of antibodies to all measles viral proteins are present in SSPE sera and CSF and to a lesser degree in MS and control sera although the non-productive SSPE strains lack one viral protein (M protein) present in wild type measles virus strains and the productive SSPE strains.

Animals↗
PubMed1982

Light-chain profiles in sera from patients with subacute sclerosing panencephalitis.

Sera from 2 subacute sclerosing panencephalitis (SSPE) patients were absorbed with a concentrated preparation of measles virus. Measles-specific IgG was eluted from the precipitates containing measles antigen-antibody complex. These IgGs, when subjected to immunofixation after isoelectric focusing showed a number of oligoclonal bands with one type of light-(L) chain. In urea polyacrylamide gel electrophoresis, the reduced and alkylated measles-specific IgG showed 1-3 homogeneous L-chain bands, whereas IgG isolated from unabsorbed sera and IgG isolated from supernatants of SSPE sera after absorption with measles virus showed a diffuse L-chain band. It can be concluded that in SSPE, measles virus is responsible for the synthesis of L-chain with restricted heterogeneity.

Animals↗
PubMed1982

Precipitation of measles virus proteins by immunoglobulin G fractions containing groups of oligoclonal bands isolated from sera of patients with subacute sclerosing panencephalitis.

Groups of oligoclonal immunoglobulin G (IgG) bands were isolated from sera of patients with subacute sclerosing panencephalitis by employing preparative isoelectric focusing. Six IgG fractions containing two to three oligoclonal bands with different isoelectric points were used to precipitate the proteins from Vero cells infected with measles virus. The results showed that all of the measles virus proteins except the M protein were precipitated by all of the IgG fractions and that the precipitation of viral proteins by the fractions containing groups of oligoclonal IgG showed slightly different patterns in some sera, whereas other sera showed no significant differences. The present study indicates that oligoclonal IgGs in subacute sclerosing panencephalitis sera are not specific to individual measles virus proteins.

Antibody Specificity↗
PubMed1982

Identification of virus-specific oligoclonal bands in subacute sclerosing panencephalitis by immunofixation after isoelectric focusing and peroxidase staining.

We developed a sensitive peroxidase staining procedure to identify oligoclonal band specificity in subacute sclerosing panencephalitis by subjecting serum and cerebrospinal fluid to isoelectric focusing and immunofixation with measles virus. The gel was washed and stained with horseradish peroxidase-conjugated goat antihuman immunoglobulin G. The samples showed dark brown measles-specific oligoclonal bands in the alkaline pH region of the gel, whereas the controls showed no significant staining. This technique may be useful in identifying specific antibody activity against viral and other antigens in oligoclonal bands in cerebrospinal fluid and serum.

Antibodies, Viral↗
PubMed1982

Oligoclonal IgG bands with and without measles antibody activity in sera of patients with subacute sclerosing panencephalitis (SSPE).

Oligoclonal IgG bands from SSPE sera were isolated by combination of Protein A-Sepharose 4B column and preparative isoelectric focusing gel procedures. Each eluted fraction, when examined in analytic IEF, showed two or three individual bands with isoelectric points close to one another, compared to approximately fifteen IgG bands seen in whole serum. When the bands were tested for measles antibody activity in immunofixation with measles virus followed by peroxidase staining, the bands eluted in pH region 8.5 to 9.3 were found to be measles specific, whereas those in pH 7.0 to 8.4 lacked significant measles activity. When eluted fractions containing groups of bands were absorbed with measles virus, the bands in pH region 8.5 to 9.3 were removed, whereas those in pH 7.0 to 8.4 region remained unchanged; this indicated that a number of oligoclonal IgG bands without measles virus activities are present in SSPE. The bands lacking measles-specific activity may be synthesized against other infectious agents or they may represent nonspecific activation of B cell clones.

Animals↗
PubMed1982

Measles-specific IgG in CSF and serum from patients with subacute sclerosing panencephalitis.

Sera and cerebrospinal fluid (CSF) from five subacute sclerosing panencephalitis (SSPE) patients were absorbed with a concentrated preparation of cell cultures infected with measles virus. The precipitates containing measles antigen-antibody complex were washed and measles-specific IgG was eluted at low pH. When the profiles of measles-specific IgG eluted from sera and the corresponding CSF were compared in immunofixation after isoelectric focusing they showed almost identical oligoclonal band patterns with respect to number, intensity, isoelectric point and light chain class. The results suggest that the same cell clones are responsible for the synthesis of measles-specific IgG in the central nervous system and serum of patients with SSPE.

Antibodies, Viral↗
PubMed1981

Serological identification of viral antigens after electrophoretic transfer.

The method described permits detection of specific antibodies to antigenic material, the protein components of which can first be separated by electrophoresis and then transferred to a supporting medium where their reactivity with antibody may be demonstrated using peroxidase-labelled anti-Ig. Results are described for measles virus and measles-like virus isolated from subacute sclerosing panencephalitis (SSPE) brain. Dilutions, incubation time and conditions, detection with peroxidase-labelled immunoglobulins and selection of substrate are described and discussed.

Antigen-Antibody Complex↗
PubMed1981

Bound antibody in multiple sclerosis brains.

Autopsy tissues of white and grey matter from brains of MS patients and controls were homogenized in PBS and centrifuged at 100,000 x g for 1 h. The residues were thoroughly washed with PBS and further extracted at acidic and alkaline pH. The eluates contained a low but significant amount of IgG, indicating that bound IgG was present in MS brains. A greater yield of IgG was obtained with alkaline pH buffer than with acidic pH buffer. In contrast, sections from 2 of 3 neurologic controls and 3 of 4 non-neurologic control failed to show detectable level of bound IgG extractable at acidic pH. These results might suggest the presence of antigen-antibody complexes in MS brains. Isoelectric focusing analysis demonstrated oligoclonal IgG bands in low pH eluates from MS brains and these bands were partly similar to those seen in neutral (unbound) pH brain extracts.

Antigen-Antibody Complex↗
PubMed1980

Absence of M protein in a cell-associated subacute sclerosing panencephalitis virus.

Measles virus has been suggested to cause subacute sclerosing panencephalitis (SSPE), a slow central nervous system disease of children. However, several questions remain about the pathogenesis of SSPE. For example, it is not known whether alteration of the measles virus genome has a role in the initiation and persistence of the disease. Several studies have compared the RNA and protein composition of wild-type (wt) and SSPE strains of measles virus in a search for markers characteristic of the latter. All the studies used SSPE strains that had reverted to the budding, virion-producing form, similar to wt. We have shown, however, that only cell-associated non-budding strains of SSPE virus cause an SSPE-like persistent infection in young ferrets. Strong cell association and cell-fusing activity were essential for the virulence of measles virus in the brains of experimental animals and possibly humans. We have, therefore, compared the protein composition of virulent SSPE strains to that of the budding, non-virulent SSPE and wt strains. We report here that the M protein was not detectable in non-budding SSPE strains D.R., Biken and IP-3, and strain D.R. contained very little H protein.

Animals↗
PubMed1980

Quantitation of measles-specific IgG. Its presence in CSF and brain extracts of patients with multiple sclerosis.

Twenty of 41 patients with multiple sclerosis (MS) and five of 30 patients with other neurological diseases had measles antibody titers in their CSF when examined in hemagglutination inhibition and neutralization tests. Quantitation of measles-specific IgG in CSF of patients with MS with significant measles antibody titers showed that less than 5% of the total IgG was measles virus specific. In contrast, using the identical quantitation procedures, 30% to 60% of the total IgG in CSF of patients with subacute sclerosing panencephalitis was found to be measles specific. Thus, only a very minor portion of the total IgG in CSF of patients with MS is synthesized against measles virus. When measles hemagglutination inhibition, complement fixation, and neutralizing antibody titers were measured in individual oligoclonal IgG bands isolated from neutral pH brain extracts of two patients with MS, low titers were present in all the oligoclonal bands rather than being restricted to any single band.

Antibodies, Viral↗
PubMed1980

Immunolabeling of SSPE and wild-type measles viruses in ferret brain cell culture.

Immunocytochemical studies using horseradish peroxidase labeled antibody were undertaken in an attempt to determine whether there are detectable antigenic differences which correlate with the biological properties of differences which correlate with the biological properties of different strains of SSPE and wild-type measles virus grown in ferret bran cell cultures. The rabbit anti-measles hyperimmune serum used in this experiment contained antibodies to all the measles virus proteins when tested by immunoprecipitation. When cells infected with the wild-type measles or productive SSPE virus strains were treated with this serum, heavy deposits of reaction product were seen on the cell membrane and virion envelope. When SSPE serum which contained relativly little antibody to the M protein was applied, a clear unlabeled area was evident just beneath the surface label. Cells infected with the non-productive SSPE strains were labeled by both sera in a spotty or discontinuous pattern on the outer surface of the cell membrane. The differences in membrane labeling seem to reflect differences in the expression of viral membrane proteins by the various SSPE and measles virus strains.

Animals↗
PubMed1980

Cellular immune response in rabbits immunized with purified Visna virus.

Visna virus-sensitized lymphocytes were demonstrated in the peripheral blood of rabbits following immunization with purified, concentrated visna virus. Lymphocytes sensitization was maximal at about 2 weeks and fell to control levels in 5 weeks. A delayed-type cutaneous hypersensitivity to the virus was observed at 2 weeks and lasted for at last 9 weeks. Both reactions increased after a booster injection. Although sera from immunized rabbits had precipitating antibodies against visna virus protein P25, their lymphocytes were not stimulated by P25. However, there was a slight reaction to P25 in the skin test. Therefore, in contrast to the humoral immune response, P25 is apparently not the most active viral antigen in the CMI response in rabbits.

Animals↗