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Biomedical subjects

O J Mellbye

Publications and source records attributed to O J Mellbye.

At least 55 records · Page 3Linked to original sources

Studies on the binding of complement factor C3 to the surface of human blood platelets.

Employing immunofluorescent staining methods, platelets from several adult patients with chronic idiopathic thrombocytopenic purpura, with systemic lupus erythematosus, and with classical rheumatoid arthritis stained positively with antisera to C3(beta 1C) and C3dg(alpha 2D). In some cases, platelet-bound C3dg antigens, but no evidence of other C3 antigens were observed. Platelets that were positive for C3 and/or C3dg were always positive for IgG or for both IgG and IgM. Platelets from normal subjects stained negatively for C3, C3dg, IgG, and IgM. Furthermore, various incubation experiments were performed to investigate the uptake of C3 and its subfragments on normal platelets. Positive platelet staining for C3 was obtained after incubation with normal and C3b-containing sera, but not after incubation with native C3. Platelets incubated with C3c(beta 1A)/C3dg-containing serum gave a positive staining for C3dg, but not for C3c. None of the sera stained positively for IgG or IgM. Thus, in contrast to platelets from several of the patients, no in vivo binding of C3 antigens on normal platelets could be established. However, in vitro they could take up both C3b and C3dg, apparently by specific binding to platelet surface structures.

Arthritis, Rheumatoid↗

T-cell immunoregulatory functions in rheumatoid arthritis patients.

We have studied the immunoregulatory function of T8+ (suppressor/cytotoxic) and Leu3a+ (inducer/helper) T cells from rheumatoid arthritis (RA) patients by measuring the effect of these T-cell subpopulations on the generation of immunoglobulin-secreting cells by normal allogeneic B cells after stimulation with pokeweed mitogen (PWM) in vitro. When T8+ or Leu3a+ cells from blood or synovial tissue from nine patients were substituted for T8+ or Leu3a+ cells, respectively, from normal blood mononuclear cells (MNC), RA T8+ cells showed an increased suppressor activity, whereas RA Leu3a+ cells were, except for one patient, weak augmentors. Unreplaced normal MNC and MNC replaced with allogeneic normal T-cell subpopulations responded equally to PWM. When T8+ plus Leu3a+ cells from the same patient replaced normal T cells, high B-cell responses were detected. Normal T8+ plus Leu3a+ cells generally supported the response to a lower degree. Substitution with two allogeneic T-cell subpopulations did not result in a B-cell response to PWM. Thus, whereas RA T8+ seemed to be strong suppressors and RA Leu3a+ cells weak augmentors by themselves, together they are possibly able to generate a B-cell stimulatory potential that might be of pathogenetic significance in the patients.

Adult↗

Immune interferon in serum and synovial fluid in rheumatoid arthritis and related disorders.

Moderate titres of antiviral activity were demonstrated in 48-58% of sera obtained from patients suffering from seropositive and seronegative rheumatoid arthritis (RA), psoriatic arthritis, Reiter's syndrome, ankylosing spondylitis, and juvenile rheumatoid arthritis. Sera from blood donors and from patients with various noninflammatory diseases were positive in 16% of cases. The activity was species-specific, mediated by the homologous cells, and destroyed by treatment with trypsin and exposure to pH 2. Antibodies against human IFN-alpha did not neutralise the activity. These characteristics are compatible with those of IFN-gamma or immune interferon. Neither the presence nor the titre of IFN was correlated with disease activity defined by concentration of C-reactive protein, C3 concentration, and erythrocyte sedimentation rate. IFN-gamma was present in 4 of 10 synovial fluids from patients with RA. The titre in one of these was higher than in the corresponding serum, indicating local production in the rheumatoid joint.

Arthritis↗

Laboratory findings in chronic prostatitis--with special reference to immunological and microbiological aspects.

Twenty-nine consecutive patients hospitalized for chronic prostatitis were examined. The HLA and radiographic findings are presented in detail elsewhere. Serum immunoglobulin levels were normal. The concentrations of IgG, IgA and IgM in prostatic fluid were significantly lower than in serum, both absolutely and as percentages of total protein concentration. Distinct bands were seen in the gamma region of agarose gel electrophoresis from prostatic fluids both in patients and in controls, and other tests also indicated that they did not reflect oligoclonal Ig responses. Growth of Chlamydia or Mycoplasma species was not detected in any of the biopsy specimens. We conclude that, with the test panel used, we have not been able to confirm that immunological factors or the presence of Chlamydia or Mycoplasma species is important in chronic prostatitis.

Adult↗

Demonstration of immunoglobulin-secreting cells in a sensitive reversed hemolytic plaque assay.

A sensitive modification of a reversed hemolytic plaque assay demonstrating individual immunoglobulin-secreting cells (ISC) is presented. The test is performed by adding test cells to a monolayer of indicator sheep erythrocytes coated with an IgG fraction of rabbit antiserum against the F(ab')2 portion of human immunoglobulins (Ig). After having added a developing antiserum and complement, hemolytic plaques with a central ISC could be counted in an inverted microscope. In addition, when ISC were killed and fixed in situ in the monolayer, the cells could be further studied by immunofluorescence of their cytoplasmic Ig.

Animals↗

Detection of T-lymphocyte subpopulation in the peripheral blood and the synovium of patients with rheumatoid arthritis and juvenile rheumatoid arthritis using monoclonal antibodies.

Monoclonal antibodies with specificities for various human T-cell antigens were used in direct immunofluorescence to quantify the proportions of T lymphocytes with suppressor/cytotoxic-cell markers and with helper/inducer-cell markers and of T lymphocytes with HLA-DR antigens. Normal percentages of lymphocytes with suppressor/cytotoxic-cell markers were detected in the peripheral blood synovial fluid and synovial tissue lymphocytes from patients with juvenile rheumatoid arthritis (JRA) and rheumatoid arthritis (RA), respectively. Normal percentages of T lymphocytes with helper/inducer-cell markers were seen in the peripheral blood of RA and JRA patients and in the synovial tissues of RA patients. Slightly decreased percentages of cells with the helper/inducer-cell marker were detected in the synovial fluids of JRA patients. The proportions of HLA-DR-positive T lymphocytes were highly increased in the synovial fluid and synovial tissue, whereas the numbers of these cells in the peripheral blood were normal. No significant differences in T gamma cells were detected between peripheral blood, synovial fluid and synovial tissue of JRA patients or between peripheral blood and synovial tissue of RA patients.

Adolescent↗

In situ characterization of mononuclear cells in rheumatoid tissues, using monoclonal antibodies. No reduction of T8-positive cells or augmentation in T4-positive cells.

The reactivity of monoclonal mouse anti-human antibodies specific for mononuclear cell surface antigens were studied by the indirect immunofluorescence technique in frozen synovial tissue sections from patients with rheumatoid arthritis (RA). Most of the proliferating synovial lining cells were positive for HLA-DR antigens and monocyte-specific antigens, since they reacted with the OKIa1 and OKM1. Cells positive for HLA-DR and monocyte antigens were also seen scattered or in small nests in the synovial stroma, probably representing synovial cells or monocytes/macrophages. Some of the HLA-DR-positive cells may also be B lymphocytes or activated T cells. Endothelial cells were also HLA-DR antigen-positive. Monoclonal antibodies with specificity for all T cells (OKT3), for helper/inducer cells (OKT4), and for suppressor/cytotoxic cells (OKT8) reacted with cells often located in follicle-like structures around vessels. Cells with the T4 phenotype tended to be located in the centre of the follicles, whereas the T8 positive cells were more peripherally situated. In most instances fewer cells were positive for the T8 than for the T4 marker. In some instances there was as many T8-positive cells as T4-positive cells. Complete lack of T-lymphocyte subpopulations was not seen.

Animals↗

Quantitation of cells secreting immunoglobulins after elution from rheumatoid synovial tissue.

Mononuclear cells (MNC) eluted from rheumatoid synovial tissue of 16 patients with rheumatoid arthritis were examined for immunoglobulin-secreting cells (ISC). Immediately after elution and separation synovial tissue MNC contained considerable numbers of ISC. IgG and IgA ISC were more abundant than IgM ISC. At the same time there were low numbers of ISC in blood. Synovial tissue ISC were lost during incubation with pokeweek mitogen (PWM), possibly because tissue MNC were already maximally triggered in vivo. This was in contrast to blood MNC, in which the number of ISC increased significantly during incubation with PWM.

Antibody-Producing Cells↗

Immunoregulatory T cells in the peripheral blood of patients with Bechterew's syndrome.

Seventeen patients with ankylosing spondylitis (Bechterew's syndrome) were investigated. Only 3 of them had detectable autoantibodies, but the IgA and IgM concentrations in serum were increased (p less than 0.05). The patients had a moderate reduction in con-A-induced suppressor cell activity of peripheral blood lymphocytes as detected in con-A/MLC assay, compared with that of 15 controls (41.0 +/- 8.6% suppression compared with 59.4 +/- 5.2%, mean +/-SEM; 0.05 less than p less than 0.1 one-sided test). No differences were found in the percentages of T gamma cells (suppressor cells) and T mu cells (helper cells) between patients an controls. This is to our knowledge the first report of con-A-induced suppressor cell activity an T lymphocyte subpopulations in the peripheral blood of patients with ankylosing spondylitis.

Adult↗

The in-vivo metabolism of C3 in ankylosing spondylitis.

Turnover studies with radioactively labelled C3 were performed in 7 patients with ankylosing spondylitis and in 14 healthy individuals . As a group the patients had a moderately higher fractional catabolic rate of C3 than the controls. A possible explanation is that the complement system is activated by immune complexes. The serum levels of C3 were high. The hypercatabolism was therefore more than compensated for by an increased synthesis rate.

Adult↗

Inflammatory synovial tissue mononuclear cells release leucocyte migration inhibition factor in antigen- and mitogen-free cultures.

The presence of leucocyte migration inhibition factor (LIF) in supernatants from apparently antigen- and mitogen-free cultures of mononuclear cells (MNC) was studied. MNC were eluted from inflamed synovial tissue or isolated from blood. Untreated supernatants, supernatants in which any LIF had been inactivated, and culture medium were compared in their ability to affect the migration of homologous polymorphonuclear leucocytes. LIF was released by synovial tissue MNC from all of the 9 patients studied, consisting of 5 patients with rheumatoid arthritis, 2 with psoriatic arthropathy, and 2 with juvenile rheumatoid arthritis. Blood MNC of the patients and of 8 healthy blood donors did not release LIF. When synovial tissue MNC supernatants from 2 patients were examined, LIF activity increased as time of incubation was extended. In at least 2 synovial tissue MNC supernatants in which LIF had been inactivated a migration enhancement activity was revealed.

Adult↗

A renal biopsy study with light and immunofluorescent microscopy in rheumatoid arthritis.

REnal biopsies were performed on 14 patients with active rheumatoid arthritis an proteinuria of whom 7 patients had reduced creatinine clearance. Glomerular hypercellularity was found in six and amyloid in seven biopsies. Immunofluorescence microscopy revealed glomerula deposits of immunoglobulins and complement in 10 of 12 biopsies, indicating an active immunologic process causing the impaired renal function.

Adolescent↗