Search PubMed⌕ Search

Biomedical subjects

E Brahn

Publications and source records attributed to E Brahn.

At least 37 records · Page 2Linked to original sources
PubMed1992

Suppression of collagen arthritis with antibodies to an arthritogenic, oligoclonal T cell line.

Rats immunized with type II collagen (CII) develop an immunologically mediated polyarthritis. T cells have been implicated in the pathogenesis of this model since they can adoptively transfer the disease. A CII-specific T cell line (VA), consisting of three distinct clones by Southern blot analysis, has been shown to be arthritogenic. Antibodies specific for this line were generated by immunizing rabbits. In an attempt to prevent collagen-induced arthritis (CIA), Louvain rats were injected with 1 ml of anti-VA ip on Days -1, +1, +3 and 0.5 ml on Day +5 (early treatment). To evaluate its effect on existing disease, rats received anti-VA on the day of arthritis onset and subsequently on 4 successive alternate days using the same dosage protocol (late treatment). Control rats received no therapeutic injections or were administered normal rabbit serum. All rats were immunized with CII on Day 0 to induce CIA. Rats administered antibodies using the early anti-VA treatment protocol had a significantly diminished incidence of arthritis compared to controls. Established arthritis was significantly diminished compared to controls in rats given the late anti-VA treatment. In both protocols, radiographic evidence of joint destruction was significantly reduced compared to controls. T cell phenotyping using flow cytometry analysis demonstrated that the anti-VA antibody therapy selectively eliminated a small subset of T cells since there was little difference in total T cell counts in the experimental versus control groups. Delayed type hypersensitivity and IgG antibody titers to CII were minimally decreased in the experimental versus control group. These results suggest that antibodies raised to an oligoclonal arthritogenic T cell line can suppress collagen arthritis. This may have implications with respect to 1) the size of the T cell receptor repertoire involved in the pathogenesis of collagen arthritis and 2) immunospecific protocols for CIA and other autoimmune diseases.

Animals↗
PubMed1992

Effects of tumor necrosis factor alpha (TNF-alpha) on collagen arthritis.

Louvain rats were administered tumor necrosis factor alpha (TNF-alpha) via a continuous osmotic infusion pump. These rats were then immunized with native type II collagen (CII) to determine the effects of exogenous TNF-alpha on collagen-induced arthritis (CIA), an animal model of rheumatoid arthritis (RA). In this highly susceptible strain, 100% of experimental and control rats developed arthritis although TNF-alpha-treated rats had more severe disease as judged by both clinical and blinded radiographic parameters. Humoral responses to collagen were high in both groups, but cellular responses to CII were augmented by TNF-alpha. Serum IL-6 levels were significantly increased in all arthritic rats. This study suggests that TNF-alpha is a proinflammatory cytokine in CIA and that future studies targeting TNF-alpha might be therapeutic.

Animals↗
PubMed1991

Suppression of collagen-induced arthritis by combination cyclosporin A and methotrexate therapy.

Louvain (LOU) rats were administered either methotrexate (MTX; 0.3 mg/kg/week or 0.8 mg/kg/week intraperitoneally), cyclosporin A (CSA; 4 mg/kg/day or 10 mg/kg/day continuous infusion via osmotic pump), or a combination of both agents. The rats were immunized with native type II collagen (CII) to determine the effects of these agents on collagen-induced arthritis, an animal model of rheumatoid arthritis. A significant decrease in the incidence (P less than 0.01) and severity of arthritis by clinical (P less than 0.05) and radiographic assessments (P less than 0.05) was found in recipients of combination therapy, compared with controls. Delayed-type hypersensitivity reactions to CII were measured on day 26, and production of IgG antibody to CII was measured on days 7, 14, and 26. IgG antibody was evident by day 7, and titers were near-maximal by day 14. Both delayed-type hypersensitivity and antibodies to CII were reduced in animals that received the higher dosage of CSA. Liver, kidney, and spleen specimens obtained from rats treated with CSA and MTX demonstrated no histologic abnormalities on light microscopy, compared with controls. These studies indicate that CSA and MTX in combination is a safe and effective therapy for collagen-induced arthritis and may be useful in the treatment of rheumatoid arthritis.

Animals↗
PubMed1991

Animal models of rheumatoid arthritis. Clues to etiology and treatment.

Animal models of rheumatoid arthritis (RA) provide useful systems for the characterization of the immunopathogenic mechanisms of chronic inflammatory synovitis. Although at least eight models have been described, the adjuvant arthritis, streptococcal cell wall-induced arthritis, and collagen-induced arthritis models have provided the most useful insights. Each of these three models has contributed clues to our understanding of RA and have yielded promising new approaches to treatment. These include combination pharmacotherapy, antigen-specific therapy, cell-specific therapy, and monoclonal antibody therapy. All of these immunotherapeutic interventions have been shown to be beneficial in one or more animal systems. This suggests that future therapies for RA and other human autoimmune diseases may be more immunoselective and, potentially, less toxic.

Animals↗
PubMed1990

Characterization of collagen-specific T cells derived from pathogenic and nonpathogenic rat T cell lines.

Rat/mouse T-T hybridomas have been developed from an arthritogenic and a nonarthritogenic T cell line. These hybridomas express alpha beta TCR and are CD4+, CD8-, and MRC OX-22-. They have type II collagen reactivity as assessed by an IL-2 release assay. Southern blot analysis of DNA extracted from these hybridomas demonstrates that each T cell line contains at least three different collagen-reactive clones. The data suggest that the spectrum of TCR beta gene rearrangements is limited, as one hybridoma from the nonpathogenic line shares an identically sized productive TCR beta gene rearrangement with two hybridomas from the pathogenic line. Both cell lines as well as one hybridoma from the pathogenic line are autoreactive to rat type II collagen. The anti-collagen responses of all the hybridomas are restricted to the rat class II MHC RT1.B gene loci. The hybridomas, like their parental cell lines, do not respond preferentially to either native or denatured type II collagen. These hybridomas recognize a specific type II collagen epitope and not repetitive collagen-like sequence motifs. They require antigen processing to respond to both native and denatured type II collagen.

Amino Acid Sequence↗
PubMed1989

Experimental synovitis induced by collagen-specific T cell lines.

Type II collagen (CII) and ovalbumin (OV) reactive T cell lines were developed from the lymph node cells of Louvain rats previously immunized with the respective antigen. Histologic sections of rat knees injected intraarticularly (ia) with 10(6) cells from line CII (VA) or CII (VII) were graded blindly. Significant synovitis (P less than 0.000001 and 0.004, respectively) was evident compared to OV line recipients. Pannus developed within 48 hr, persisted for at least 4 to 6 weeks, was inducible with fewer than 10(3) CII cells, and required viable lymphocytes. The process was independent of anticollagen antibodies and was associated with the lines' capacity to elaborate a previously described 65-kDa CII-binding arthritogenic lymphokine. Line CII (VIII), which could not elicit a synovitis, did not produce detectable quantities of this factor. A line- and antigen-specific synovitis, comparable to the ia injection protocol, was also induced by intravenous administration of 2 x 10(7) CII (VA) cells and ia challenge with soluble collagen. These studies demonstrate that CII lines bearing the T helper phenotype can evoke a sustained synovitis and suggest that this experimental process is associated with the release of an arthritogenic lymphokine and not dependent on the formation of antibodies to CII.

Animals↗
PubMed1989

Systemic lupus erythematosus and concurrent cytomegalovirus vasculitis: diagnosis by antemortem skin biopsy.

A 45-year-old woman with a 4-year history of systemic lupus erythematosus (SLE) developed fever, decreased visual acuity and skin ulceration. A biopsy of a cutaneous ulcer demonstrated small vessel vasculitis with characteristic cytomegalovirus (CMV) inclusions in the vascular endothelium. The presence of CMV was confirmed by DNA hybridization immuno-histochemistry. Retinal artery vasculitis, previously associated with flares of her SLE, was also noted on ophthalmologic examination. Our case demonstrates that CMV infection can mimic the cutaneous manifestations of collagen vascular disease and that early identification can be made by biopsy of suspicious skin lesions.

Biopsy, Needle↗
PubMed1988

Detection of arthritogenic factor in adjuvant arthritis.

An evocation of arthritis by an Ag-specific lymphokine has recently been considered with the description of arthritogenic factor (AF) in rats with collagen arthritis. Because rats with CFA-induced arthritis also exhibit T cell reactivity to native type II collagen, T cell lines specific for this protein were established from CFA-injected rats. Supernatant material from these lines contained a type II collagen-binding lymphokine with functional and biochemical attributes identical with those described for AF, i.e., it was a 65-kDa species cross-reacting immunoprotein possessing the ability to incite an erosive, proliferative synovitis when injected into the knee joint of naive recipients. Similarities were also observed with HPLC and on two-dimensional gels. Lymph node cells from rats with arthritis created by injection of the synthetic adjuvant, CP-20,961 failed to produce AF, suggesting that this material is not a ubiquitous concomitant of inflammatory arthritis in the rat. Test injections into sites contiguous with the ear cartilage plate and into fibroblast-lined s.c. pouches suggested that cartilage was a requisite for the induction of inflammation by AF. These data identify a potentially shared effector pathway in the collagen and adjuvant models. The presence of AF in two frequently used models further supports the hypothesis that Ag-specific lymphokines can create autoimmune disease.

Animals↗
PubMed1988

Intraarticular injection of arthritogenic factor causes mast cell degranulation, inflammation, fat necrosis, and synovial hyperplasia.

Arthritis resembling human rheumatoid arthritis is produced in rats either by immunization with type II collagen or injection of complete Freund's adjuvant. The development of arthritis in both models may be mediated by a T cell-derived, type II collagen-specific protein that has been termed arthritogenic factor. Here, the morphologic changes produced after intraarticular injection of this factor were determined. T cell lines were derived from type II collagen-immunized rats. Arthritogenic factor was isolated from culture supernatants by affinity chromatography on type II collagen-conjugated Sepharose and injected into rat knees. The synovium covering the infrapatellar fat pad was examined by light and electron microscopy at 6 hours to 7 days after injection. By 6 hours, the synovium and fat pad were edematous and heavily infiltrated with neutrophils and a few mononuclear cells. Fibrin was present in the synovium and joint space. Most mast cells had partially degranulated. By 24 hours, the infiltrate became primarily mononuclear and fewer neutrophils were seen. Fat necrosis and edema occurred in the subsynovium. By 48 hours and 7 days, the synovium was hyperplastic, some fibrin persisted, and macrophages were present. Control knees, injected with material obtained from T cell lines established with the antigen, ovalbumin, and subjected to type II collagen affinity chromatography, had less fibrin deposition, milder cellular infiltrates, and less mast cell degranulation than knees injected with arthritogenic factor. These studies suggest that arthritogenic factor stimulates acute cellular infiltration and mast cell secretion which is followed by fat necrosis, synovial hyperplasia, and mononuclear cell infiltration.

Adipose Tissue↗
PubMed1987

Attenuation of collagen arthritis and modulation of delayed-type hypersensitivity by type II collagen reactive T-cell lines.

T-cell lines were established from the lymph node cells of syngeneic Louvain (LOU) rats previously immunized with native chick type II collagen (CII) emulsified in incomplete Freund's adjuvant. The CII lines proliferated in vitro to type II collagen but not to type I collagen, ovalbumin (OV), or PPD. Control lines, developed from LOU rats immunized with OV emulsified in complete Freund's adjuvant, were OV specific because they did not respond to other antigens in vitro. CII line cells could adoptively transfer delayed-type hypersensitivity (DTH) but did not induce IgG antibody production to collagen. Moreover, the intravenous administration of 2 X 10(7) CII line cells prevented the subsequent induction of collagen arthritis following immunization and suppressed DTH to collagen without affecting antibody responses in the recipients. Spleen cells, but not sera, from these resistant rats decreased CII line reactivity in vitro. OV or irradiated CII lines had no effect on clinical or immunologic parameters in this model. These findings demonstrate protection from arthritis afforded by T-cell line transfer and suggest that the phenomenon results from down-regulation of the recipients' cellular immunity to collagen.

Animals↗
PubMed1985

An arthritogenic lymphokine in the rat.

A type II collagen-specific arthritogenic lymphokine has been identified in the rat. Arthritogenic factor (AF) is a 65 kD protein generated in vitro by T cells from rats with collagen arthritis, and it induces an erosive, proliferative synovitis when injected into the knee joint of syngeneic naive recipients. Complement does not appear to be required. These data identify a potential T cell-mediated effector mechanism in this model, and suggest that AF may function in other inflammatory synovial diseases.

Animals↗
PubMed1984

Total lymphoid irradiation therapy in refractory rheumatoid arthritis. Fifteen- to forty-month followup.

Twelve patients with refractory rheumatoid arthritis were treated with total lymphoid irradiation (TLI) to a total cumulative dose of 3,000 rads. Post-TLI morbidity/mortality included 8 patients with xerostomia, 4 with weight loss of greater than 10 kg, 3 with loss of 4 or more teeth, 3 with herpes zoster, 4 with bacterial infection that was fatal in 2, 3 with hypothyroidism, 1 with cutaneous vasculitis, and death from myocardial infarction in 1 patient and cardiorespiratory arrest in another. Ten of the patients were reevaluated 15-40 months (mean +/- SE, 30 +/- 2) after completion of TLI, and significant improvement was noted in several disease parameters including number of swollen joints, duration of morning stiffness, and 50-foot walking time. Blood lymphopenia and a decrease in helper T cells (T4) were also noted. These data suggest that changes in immunoregulation induced by TLI can produce longlasting alterations in rheumatoid arthritis, although adverse effects may limit its efficacy.

Adult↗
PubMed1984

Effect of antithymocyte serum on collagen arthritis in rats: evidence that T cells are involved in its pathogenesis.

To assess the role of T cells in collagen arthritis, a heterologous T cell-specific antiserum (ATS) was administered intraperitoneally to female Wistar-Furth rats. ATS treatment on Day -1, 1, 3, and 5 and immunization with native chick type II collagen on Day 0 resulted in a decreased incidence of arthritis (5 of 19, 26%) compared to immunized rats given either nonimmune heterologous serum on these days (20 of 25, 80%) or ATS injected on Day 5, 7, 9, and 11 (17 of 20, 85%) (P less than 0.001 for both comparisons). The early-ATS protocol also was associated with a delayed onset and reduced disease severity in the few rats in this group that did develop arthritis. Both delayed-type hypersensitivity (DTH) and serum IgG antibody titers to native type II collagen, measured on Day 10, were decreased significantly (P less than 0.002) in rats administered ATS beginning on Day -1 compared to the other two groups. These data suggest that T cells contribute to the inception of collagen arthritis and that their critical function occurs within the first 5 days after immunization.

Animals↗
PubMed1984

Antigen-specific suppression of collagen arthritis by adoptive transfer of spleen cells.

Wistar-Furth (W-F) rats were given 10(9) syngeneic spleen cells, suspended in Hanks' balanced salt solution (HBSS), intravenously on Day 0 to investigate the mechanisms involved in antigen-specific suppression of collagen arthritis. These cells were pooled from W-F donors which had been injected iv on Days -21, -14, and -7 with rat red blood cells (RBC) coupled with glutaraldehyde to either native chick type II collagen, denatured type II collagen, or native type I collagen. All recipients were immunized with an emulsion of native type II collagen in incomplete Freund's adjuvant on Day 1 to induce collagen arthritis. There was a decreased incidence of arthritis, by clinical and radiographic assessments, in rats receiving spleen cells from donors previously administered native type II collagen-coupled RBC compared to those given spleen cells obtained from donors treated with denatured type II or native type I collagen-coupled RBC [18 of 30 (60%) arthritic vs 20 of 20 (100%) and 19 of 20 (95%) arthritic, for the three groups, respectively, P less than 0.01 for both comparisons]. The incidence of arthritis in 35 rats administered HBSS iv 1 day prior to immunization (83%) and 10 immunized rats given no iv injections (100%) was also significantly higher (P less than 0.05) than the incidence in the antigen-relevant experimental group. Hemagglutinating antibody titers and delayed-type hypersensitivity (DTH) to collagen were lower in the recipients of cells from donors administered native type II collagen-coupled RBC, whereas IgG antibody titers to collagen were unaltered. These results demonstrate that passively transferred spleen cells can attenuate collagen arthritis and sensitization in an antigen-specific manner.

Animals↗
PubMed1982

Trichosporon cutaneum endocarditis: a sequela of intravenous drug abuse.

A 42-year-old abuser of intravenous drugs developed fulminant aortic insufficiency necessitating a prosthetic valve replacement. Trichosporon cutaneum was isolated from the surgical specimen. The patient received a total of 3,195 g of amphotericin B, and 148 g of 5-fluorocytosine during his four-month hospitalization. He manifested no additional signs of persistent fungal infection, but died one year later from an intracerebral hemorrhage.

Adult↗