[The medical doctor-degree under revision].
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Biomedical subjects
Publications and source records attributed to E Rødahl.
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We have analyzed the capacity of sensory and autonomic ganglia to demonstrate latency-associated transcripts (LATs) following inoculation of the anterior chamber of the mouse eye with Herpes simplex virus type 1 (HSV-1). In autonomic ganglia, the number of LAT-containing neurons decreased 50-fold or more from the acute to the latent phase, while in the trigeminal ganglion, the decrease was less than 2-fold. The decrease in autonomic ganglia could not be related to destruction of neurons expressing LATs, since these ganglia harbored substantial amounts of viral DNA. The data demonstrate that during the latent phase of the infection, accumulation of LATs varies depending on the type of infected neuron and suggest that some neurons may harbor a latent infection in the absence of LAT expression.
Rabbit antisera against the major internal protein, p27, of retrovirus-like particles from psoriatic urine, and against the serologically cross-reacting antigen, pso p27, from psoriatic scale, reacted with the Fc part of human IgG. Evidence indicating that the p27 antigen and the pso p27 antigen are identical has been presented in previous reports. A commercial antiserum against human IgG recognized a component in the pso p27-containing solution used as the source of antigen for immunization of the rabbits. By means of monoclonal antibodies against the pso p27 antigen, it was demonstrated that the Fc-reacting antibodies, and the antiserum against human IgG, recognized an epitope on the pso p27 antigen. The data indicated that an antigenic determinant is shared by the p27 antigen(s) and human IgG, suggesting that p27 antigen(s) may act as antigen(s) eliciting the production of antibodies with rheumatoid factor activity in psoriatic patients.
This paper describes various hypotheses for the origin of viruses, prerequisites for the introduction of a virus into a host population, and the concerted evolution of virus and host. In general, viruses evolve through mutations and genetic recombinations. Selection pressure is exerted by various host defence mechanisms and possible ways of virus transmission. The virus variants showing a high reproduction rate without killing their host are most likely to be selected for. In addition, the viral infection vice versa exert a selection pressure on the host population resulting in the elimination of highly susceptible individuals and an increased number of resistant individuals. The apparent consequence is a tendency for the virus to be less virulent and the host to be more resistant.
Autoimmune disorders comprise a broad spectrum of diseases. This paper describes the development of immunological tolerance, and presents a review of known and possible mechanisms for the development of autoimmune reactions and autoimmune disorders.
Retroviruses have been proposed as etiologic agents for the development of chronic arthritis in humans. The arthritis seen in goats infected by caprine arthritis encephalitis virus and the spontaneous arthritis of inbred MRL/l mice illustrate how retroviruses may cause the development of a disorder closely resembling human rheumatoid arthritis. Several investigators have searched for evidence of retrovirus infection in patients with chronic arthritis, but in most cases the results have been disappointing. However, in 1983, Iversen isolated a virus-like particle from a patient with psoriasis. The particle had a buoyant density in sucrose and a protein composition that closely resembled murine and primate retroviruses. Particle proteins participate in immune complex formation in psoriasis, in psoriatic arthritis, and in ankylosing spondylitis. Particle proteins are also present in deposits in psoriatic lesions and in affected synovial tissue resembling immune complex deposits. The possible role for retrovirus-like antigens in the inflammatory process in psoriasis and seronegative arthritis is discussed.
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Analysis of five serum samples and three synovial fluids from patients with ankylosing spondylitis (AS) and five serum samples from healthy blood donors for the presence of antibodies cross reacting with the Fc part of rabbit IgG (rheumatoid factors (RFs] using an isotype specific, enzyme linked immunosorbent assay (ELISA) showed only insignificant amounts of free RFs, while IgG RFs were observed in alkaline dissociated circulating immune complexes (CICs). Only insignificant amounts of free antibodies reacting with the psoriasis associated antigen pso p27 could be detected in the samples, while extensive amounts of IgG antibodies and moderate amounts of IgM antibodies reacting with pso p27 were detected in alkaline dissociated CICs from the patients. Pso p27 has been reported to share a common determinant with the Fc part of human IgG. Removal of the RF activity from the CICs of patients with AS by absorption with IgG resulted in a decrease of the anti-pso p27 activity. Monoclonal anti-pso p27 antibodies in a sandwich ELISA were used to detect antigens cross reacting with pso p27. A positive reaction was observed in all serum CICs and in one of the synovial fluid CICs. The data indicate that antigens related to pso p27 participate in CIC formation in AS and may also be responsible for the elicitation of rheumatoid factors in patients with AS.
Circulating immune complexes (CIC) were isolated from patients with ankylosing spondylitis (AS) and healthy blood donors by isopycnic ultracentrifugation in sucrose gradients. The CIC were analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. The major components of the CIC were identified as albumin, immunoglobulins, and complement factors. A 70 kD component and several low molecular weight components (Mr 19 kD and 14 kD (doublet] were detectable only in CIC from patients with AS. An antiserum raised against the envelope glycoprotein, gp70, of a psoriasis associated retrovirus-like particle was applied to check for cross reacting activity. This antiserum reacted with both a 70 kD and a 40-45 kD component in CIC from three out of six patients but not with CIC from any of the blood donors.
A rabbit antiserum against the major internal protein, p27, of a psoriasis associated retrovirus-like particle has been used in indirect fluorescence microscopy of biopsies from psoriatic skin. The analysis indicate expression of p27 antigen in epithelial cells in psoriatic lesions and in clinically uninvolved psoriatic skin. A reaction of the antiserum with dermal vessel walls in the lesion was also observed.
The major internal protein, p27, of a retrovirus-like particle isolated from the urine of a patient with psoriasis has been purified and used in an indirect ELISA to detect human antibodies against the virus antigen. Rabbit anti-p27 antiserum has been applied to detect p27 antigen present in clinical specimens. p27 and anti-p27 antibodies have been demonstrated in extracts from psoriatic scales. Insignificant amounts of free anti-p27 antibodies are present in serum, but both p27 and anti-p27 antibodies have been detected in circulating immune complexes obtained from serum or synovial fluid from patients with psoriatic arthritis.
Isopycnic ultracentrifugation is frequently applied for preparative isolation of macromolecules. Using bovine serum albumin (BSA)-anti-BSA antibody complexes as a model system, isopycnic banding of complexes was observed in CsCl, Nycodenz, and sucrose gradients. In CsCl gradients, free antigen or antibody could not be separated from the immune complexes. Variations in antigen to antibody ratio from equivalence and in the amount of complement present during complex formation resulted in zone broadening and banding at slightly lower densities in Nycodenz. This was not observed in sucrose. Serum immune complexes were isolated from patients with rheumatoid arthritis or ankylosing spondylitis. Banding of in vivo-formed immune complexes was observed more frequently in sucrose than in Nycodenz.
In the application of the anti-Clq, the anti-C3, or the conglutinin-binding assay for the detection of complement-fixing circulation immune complexes in patients with ankylosing spondylitis or healthy blood donors, antibodies cross-reacting with the solid-phase bound agent were observed in several sera, resulting in erroneous interpretation of the tests. Corrections for the interfering antibodies were made by testing for the binding to conglutinin both in the presence and in the absence of Ca++, while the anti-Clq and the anti-C3 assays included the application of F(ab')2 fragments of normal IgG to check for anti-F(ab)2 anti-bodies.
A rabbit antiserum against the major internal protein, p27, of a psoriasis associated retrovirus-like particle has been applied in an immunofluorescence assay for the detection of antigens cross reacting with p27 in patients with psoriatic arthritis, seronegative rheumatoid arthritis, or ankylosing spondylitis. Antigens reacting with anti-p27 antibodies were present in lymphocytes from blood or synovial fluid from all patients examined. However, the expression was restricted to 0.01-0.1% of the cells. Among the positive p27 cells were cells reacting with markers for T, B, or NK cells. The anti-p27 antibodies also reacted with mononuclear cells in the synovial membrane and with the internal wall of some small or medium sized vessels in sections of synovial biopsy specimens from the patients with chronic arthritis. The reaction with mononuclear synovial membrane cells was restricted to approximately 0.1% of the cells. Blood lymphocytes or synovial sections from healthy persons did not react with the anti-p27 antibodies. The implication of these observations in the pathogenesis of chronic arthritis in man is discussed.