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Biomedical subjects

H Thormar

Publications and source records attributed to H Thormar.

At least 19 recordsLinked to original sources
PubMed1995

Inhibition of visna virus replication and cytopathic effect in sheep choroid plexus cell cultures by selected anti-HIV agents.

Several anti-HIV agents were tested against visna virus replication and cytopathic effect (CPE) in sheep choroid plexus cell cultures. Sulphated polysaccharides (i.e., dextran sulphate, pentosan polysulphate and heparin) and plant lectins, which inhibit viral adsorption and fusion, were found to be 10- to 40-fold less active against visna virus than against HIV. Bicyclam derivatives were at least 250-fold less active against visna virus and the highly HIV-1 specific TIBO derivatives were without a significant inhibitory effect on visna virus at subtoxic concentrations. In contrast, several 2',3'-dideoxynucleosides and acyclic nucleoside phosphonate analogues, which inhibit reverse transcription, were found to be very effective inhibitors of visna virus replication and viral CPE in cell culture.

Animals↗
PubMed1990

Measles virus-specific immunoglobulin D antibody in cerebrospinal fluid and serum from patients with subacute sclerosing panencephalitis and multiple sclerosis.

Quantitation of measles-specific immunoglobulin D (IgD) antibody was carried out in cerebrospinal fluid (CSF) and serum samples from 18 patients with subacute sclerosing panencephalitis (SSPE), 12 patients with multiple sclerosis (MS) and seven normal controls with high measles antibody titers in serum, using polyclonal and monoclonal antibodies specific for human IgD and enzyme-linked immunosorbent assay. Measles-specific IgD activity was significantly higher in CSF and serum from SSPE patients compared to that found in patients with MS or normal controls. The IgD antibody to measles virus was not due to high levels of measles-specific IgG since significant measles IgD activity was found after eluting IgG from SSPE serum. The increased level of measles-specific IgD found in SSPE sera is consistent with the levels observed in patients with acute and chronic viral infections.

Enzyme-Linked Immunosorbent Assay↗
PubMed1990

Antiviral and antibacterial lipids in human milk and infant formula feeds.

Human milk and two infant formula feeds were tested for antiviral and antibacterial activity before being given to 21 low birthweight (LBW) infants; neither was present. When samples were aspirated from the stomachs of the infants within one to three hours of feeding, however, they reduced titres of enveloped virus and also killed both Staphylococcus epidermidis and Escherichia coli. The lipid fraction of the gastric aspirate from an infant who had been given human milk as well as those from four infants who had been given a conventional LBW infant formula feed, showed antiviral and antibacterial activities at least equal to the activities of the unfractionated aspirates. There was no consistent difference in antiviral or antibacterial activity of either the stomach aspirates or the lipid fractions of these aspirates between infants given human milk and those given formula feeds. The antiviral and antibacterial activities of the gastric aspirates seem to result from intragastric production of monoglycerides and fatty acids from the triglyceride content of the ingested feeds.

Antiviral Agents↗
PubMed1989

Immunoglobulin G subclass antibodies to measles virus in patients with subacute sclerosing panencephalitis or multiple sclerosis.

Mouse monoclonal antibodies specific for human immunoglobulin G (IgG) subclasses and a sensitive immunoassay were used to evaluate the IgG subclass antibody response to measles virus antigens in cerebrospinal fluid and serum samples from 20 patients with subacute sclerosing panencephalitis (SSPE), 12 patients with multiple sclerosis (MS), and 11 controls with high measles virus antibody titers in serum. In patients with SSPE, measles virus-specific antibodies were found mainly in the IgG1 subclass and the IgG subclass distribution remained unchanged, irrespective of the clinical stage or duration of the disease. In patients with MS and in controls, measles virus activity was also associated mainly with IgG1. However, the activity was significantly lower than that found in patients with SSPE. The results suggest that there is no primary abnormality in humoral immune response to measles virus in patients with MS. The disproportionately high levels of the measles virus-specific IgG1 subclass found in patients with SSPE may be due to persistent antigenic stimulation or reflect a defect in immunoregulatory mechanisms in response to viral infection.

Adolescent↗
PubMed1988

Transmission of measles virus encephalitis to ferrets by intracardiac inoculation of a cell-associated SSPE virus strain.

Ferret fibroblasts infected with a cell-associated strain of subacute sclerosing panencephalitis virus were inoculated into the hearts of ferrets in order to study whether the virus can spread from the blood to the brain in this animal model. Five of 21 inoculated ferrets developed encephalitis 5-7 days later and were sacrificed. Sick animals showed inflammatory lesions in the brain, both perivascular cuffings and infiltration of inflammatory cells in the choroid plexus and meninges. Virus was isolated in cell cultures from various parts of the brain and virus antigen was found by immunostaining, particularly in the cortex. Virus was not detected in inflammatory cells by immunostaining but in situ hybridization with a cDNA probe demonstrated measles virus RNA in neurons and glia cells surrounding perivascular inflammatory cuffings and in a lymph node of one ferret. Ferrets inoculated into the heart with cell-associated SSPE virus seem to be a suitable animal model to study how the virus spreads from the blood to the brain.

Animals↗
PubMed1987

Measles virus matrix protein gene expression in a subacute sclerosing panencephalitis patient brain and virus isolate demonstrated by cDNA hybridization and immunocytochemistry.

Subacute sclerosing panencephalitis (SSPE) is a rare, fatal disease of children caused by a persistent measles virus infection of the central nervous system. A defect in synthesis of measles virus matrix (M) protein may be a factor in virus persistence in the brain. This study details attempts to detect expression of M protein in the brain of an SSPE patient, in the cell-associated virus isolated from this brain, and in brains of ferrets inoculated with the isolate. In situ hybridization with a tritiated cloned cDNA probe was used to search for RNA encoding M protein. Immunostaining with monospecific antiserum and the avidin-biotin-peroxidase technique was done to locate the polypeptide. The data obtained indicate that although nucleotide sequences coding for M protein were detected in the patient and ferret brains, expression of M protein in these tissues could not be detected. In the culture SSPE virus isolate, the results were the same until the infected cells were examined by electron microscopy and a very limited expression of M protein was revealed. This suggests either diminished synthesis and/or rapid degradation of M protein in this cell-associated virus strain.

Adolescent↗
PubMed1987

Inactivation of enveloped viruses and killing of cells by fatty acids and monoglycerides.

Lipids in fresh human milk do not inactivate viruses but become antiviral after storage of the milk for a few days at 4 or 23 degrees C. The appearance of antiviral activity depends on active milk lipases and correlates with the release of free fatty acids in the milk. A number of fatty acids which are normal components of milk lipids were tested against enveloped viruses, i.e., vesicular stomatitis virus, herpes simplex virus, and visna virus, and against a nonenveloped virus, poliovirus. Short-chain and long-chain saturated fatty acids had no or a very small antiviral effect at the highest concentrations tested. Medium-chain saturated and long-chain unsaturated fatty acids, on the other hand, were all highly active against the enveloped viruses, although the fatty acid concentration required for maximum viral inactivation varied by as much as 20-fold. Monoglycerides of these fatty acids were also highly antiviral, in some instances at a concentration 10 times lower than that of the free fatty acids. None of the fatty acids inactivated poliovirus. Antiviral fatty acids were found to affect the viral envelope, causing leakage and at higher concentrations, a complete disintegration of the envelope and the viral particles. They also caused disintegration of the plasma membranes of tissue culture cells resulting in cell lysis and death. The same phenomenon occurred in cell cultures incubated with stored antiviral human milk. The antimicrobial effect of human milk lipids in vitro is therefore most likely caused by disintegration of cellular and viral membranes by fatty acids. Studies are needed to establish whether human milk lipids have an antimicrobial effect in the stomach and intestines of infants and to determine what role, if any, they play in protecting infants against gastrointestinal infections.

Animals↗
PubMed1986

Membrane-disruptive effect of human milk: inactivation of enveloped viruses.

Fresh human milk treated with antibody to secretory IgA had no effect on viral infectivity but became antiviral after 1 hr in the stomachs of suckling infants. Antiviral activity also appeared in fresh milk stored at 4 C for at least two days. The antiviral activity, which reduced titers of virus by as much as 10,000-fold, only affected enveloped viruses and was localized in the milk lipid fraction. Its appearance in stored milk was apparently due to fatty acids released by the activity of milk lipases, particularly lipoprotein lipase. Antiviral activity in the infants' stomach, however, most likely resulted from the activity of gastric and lingual lipases on milk triglycerides and caused the release of antiviral fatty acids. Milk and stomach contents that were antiviral also lysed cultured cells by disruption of their plasma membrane. Cell lysis was also caused by purified linoleic acid, which is a normal constituent of human milk triglycerides.

Antibodies, Anti-Idiotypic↗
PubMed1985

Demonstration of immunoglobulin in brains of ferrets inoculated with an SSPE strain of measles virus: use of protein A conjugated to horseradish peroxidase.

Measles virus-specific immunoglobulin G (IgG) has been found in the brains of patients with subacute sclerosing panencephalitis (SSPE), a slowly progressing central nervous system (CNS) disease affecting children. IgG/albumin ratios indicate that the antibodies are probably synthesized in the CNS. In a ferret model system, protein A conjugated to horseradish peroxidase (PrAPx) was used to localize Ig's in brains of animals inoculated with a cell associated strain of SSPE. Ig's were found in plasma cells in various stages of antibody production both in perivascular inflammatory lesions and scattered throughout the cerebral cortex. These findings offer corroborative evidence that the Ig found in SSPE ferret brain and CSF is actively synthesized within the CNS. Antibody was also demonstrated in glial and neuronal cell bodies and processes and in postsynaptic profiles. These are the same sites where measles virus antigens are most frequently found and suggests the possibility of immune complex formation.

Animals↗
PubMed1985

Localization of measles virus antigens in subacute sclerosing panencephalitis in ferrets.

Young adult male ferrets were inoculated intracerebrally (i.c.) with a cell-associated encephalitogenic subacute sclerosing panencephalitis (SSPE) virus strain to study the pathogenesis of the disease at the ultrastructural level. Most became acutely ill in 8-13 days. Areas of the brain were examined with indirect immunoperoxidase labeling techniques to detect measles antigen. None of these animals showed the characteristic viral nucleocapsids or marked inflammatory response associated with SSPE. However, all had positive immunolabeling of unstructured virus antigen, especially in post-synaptic regions in all areas of the brain that were examined. One ferret, immunized with measles vaccine 40 days prior to challenge with SSPE, became ill 18 days post inoculation (p.i.). Perivascular cuffings of inflammatory cells and large cytoplasmic inclusions of fuzzy nucleocapsids were found in the brain and spinal cord. The study indicates that ferrets which become acutely ill after inoculation with cell-associated SSPE virus do so before there is a marked cellular immune response or formation of virus nucleocapsids.

Animals↗
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.

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Animals↗