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Biomedical subjects

F C Breedveld

Publications and source records attributed to F C Breedveld.

At least 415 records · Page 23Linked to original sources

Influence of donor characteristics on responsiveness of mononuclear cells to pokeweed mitogen.

The variability in response of peripheral blood mononuclear cells (PBMC) from 95 healthy donors to pokeweed mitogen (PWM) was investigated. Age, sex, and blood group of the donors, the numbers of PBMC recovered from 500 ml blood, the percentage of monocytes therein, the presence of antilymphocyte antibodies (L-Cyt), or of anti-cytomegalovirus (CMV) antibodies, as well as HLA-B8 and HLA-DR4 were evaluated for their relation with the level of blast cell formation, proliferative response, and immunoglobulin G (IgG) synthesis, induced by PWM. The results showed that increasing age of the donors and the presence of anti-CMV antibodies are significantly associated with low proliferative responses of PBMC, whereas the HLA-B8 antigen and female donor sex were found to be associated with high blast cell formation after PWM stimulation. High percentages of monocytes in isolated PBMC at the onset of stimulation were inversely associated with IgG production, whereas the HLA-DR4 antigen was associated with high levels of IgG production, induced by PWM. The observed relations indicate that for comparison of responses of unseparated PBMC to PWM between patients and healthy controls, age, sex, and laboratory data, including the HLA background of donors, may have to be taken into account.

Adult↗

Imaging of inflammatory arthritis with technetium-99m-labeled IgG.

The accumulation of nonspecific polyclonal human immunoglobulin G (IgG) radiolabeled with 99mTc was compared to that of [99mTc]albumin and [99mTc]nanocolloid in rats with collagen induced arthritis. Serial scintigrams were acquired directly, 4 and 24 hr after injection. A clearly discernable image of the site of synovitis was seen with [99mTc]IgG as early as 4 hr postinjection. The relative intensity of the inflammatory lesion was maximal at 24 hr. Discrimination between arthritic and nonarthritic joints as well as correlations between the relative intensity of the arthritic joint and clinical indices of joint inflammation were superior with IgG compared to albumin or nanocolloid. These studies show that localization and severity of inflammatory joint disease can be detected with radiolabeled nonspecific IgG.

Animals↗

Anti-endothelial cell antibodies in patients with rheumatoid arthritis complicated by vasculitis.

IgG antibodies reactive with human umbilical vein endothelial cells were found in 19 out of 28 patients with rheumatoid vasculitis (RV), in four out of 24 patients with rheumatoid arthritis (RA), in seven out of 10 patients with systemic lupus erythematosus (SLE), but not in healthy donors. In four patients with RV who were followed longitudinally, regression of vasculitic episodes coincided with decreasing titres of anti-endothelial antibodies (AEA). Binding activity to endothelial cells was observed in intact IgG and F(ab')2 fragments of IgG. AEA activity was unrelated to antibodies against nuclear, blood group or major histocompatibility complex antigens and did not involve immune complexes. AEA activity was not specific for endothelial cells since the AEA-positive sera and the IgG fractions prepared from these sera also reacted with fibroblasts. Adsorption of positive sera and corresponding IgG fractions with endothelial cells decreased the IgG binding reactivity on both fibroblasts and endothelial cells. These findings show that RV patients have IgG-AEA, and suggest that these antibodies may play a role in the pathogenesis of the disease.

Antibody Specificity↗

Synovial fluid T cell reactivity against 65 kD heat shock protein of mycobacteria in early chronic arthritis.

The in vitro proliferative response against a recombinant 65 kD Mycobacterium bovis protein that has 100% homology with the 65 kD protein of M tuberculosis was tested in synovial fluid and peripheral blood mononuclear cells from patients with rheumatoid arthritis (RA) and other types of chronic arthritis. An acetone precipitate (AP) of M tuberculosis, and a purified protein derivative (PPD) of M tuberculosis were also tested. Responsiveness of synovial fluid lymphocytes to the mycobacterial antigens was found both in patients with RA and in patients with other forms of chronic inflammatory arthritis, but not among controls. T cell reactivity against mycobacterial antigens was nearly always higher in synovial fluid than in peripheral blood in those patients who showed reactivity. A significant association was found between responsiveness of synovial T cells to the 65 kD protein and AP, but no relation between responsiveness to the 65 kD protein and PPD. Both the number of 65 kD protein responders and the mean proliferative response of synovial T cells to the 65 kD protein were inversely correlated with duration of joint inflammation. Thus, a 65 kD-protein-specific reactivity of synovial T cells, mainly present in an early stage of joint inflammation, may be responsible for triggering chronic arthritis.

Adolescent↗

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↗

Frequency of infection among patients with rheumatoid arthritis versus patients with osteoarthritis or soft tissue rheumatism.

We compared the frequencies and types of infections that occurred in 448 patients with rheumatoid arthritis (RA) versus those occurring in 185 control patients who had osteoarthritis or soft tissue rheumatism. At least 1 infection developed in 23% of the RA patients and in 27% of the control patients. Using a series of risk factors, we found no substantial difference in the risk of infection in RA patients compared with that in control patients. Some of these factors, such as being female, having poor functional capacity, and receiving glucocorticoid treatment, were associated with different levels of risk for infection, but the levels were similar in RA patients and control patients.

Arthritis, Rheumatoid↗

Immune complexes in sera from patients with rheumatoid vasculitis induce polymorphonuclear cell-mediated injury to endothelial cells.

The ability of sera from 11 patients with rheumatoid arthritis (RA) complicated by leukocytoclastic vasculitis (RV) to induce injury to cultured monolayers of human umbilical vein endothelial cells (HEC) was investigated. Injury was assessed in vitro using assays of cell lysis and cell detachment. Sera from patients with RV produced neither direct injury to HEC monolayers nor indirect injury when cocultured with HEC and normal peripheral blood polymorphonuclear cells (PMN). However, immune complexes (Icx) isolated from these sera induced nonlytic PMN-mediated HEC detachment. The inhibitory effect of serum on PMN-mediated HEC detachment induced by Icx could be attributed both to a different response of PMN to Icx present in serum compared to isolated Icx and to the presence of protease inhibitors in serum. The results of this study show that sera from patients with RV do not contain factors that can injure HEC directly and provide further support for the hypothesis that Icx and PMN play important roles in the pathogenesis of immune vascular injury.

Adult↗

Neutropenia and infections in Felty's syndrome.

Fifteen patients with Felty's syndrome (FS) were studied prospectively during a 3-year period to determine the influence of multiple haematologic parameters on the incidence of infections. An increased risk of recurrent major and minor infections was primarily related to peripheral blood polymorphonuclear cell (PMN) counts of less than 0.1 x 10(9)/l. Bone marrow lymphocytosis, a decreased percentage of PMN in bone marrow differential counts and an impaired in vitro growth of colony-forming unit-PMN macrophage were also related to an increased incidence of infection but were predominantly present in patients with less than 0.1 x 10(9)/l circulating PMN. The maximal response in the number of circulating PMN measured after injection of epinephrine and hydrocortisone varied substantially within patients, but those with less than 0.1 x 10(9)/l PMN always had lower responses than those with greater than 0.1 x 10(9)/l PMN. These variables did not therefore contribute to the identification of FS patients at risk of infection.

Agranulocytosis↗

Errors in the prediction of creatinine clearance in patients with rheumatoid arthritis.

The accuracy of two equations used to predict creatinine clearance was assessed in 27 patients with rheumatoid arthritis (RA) and 34 controls. Both equations were accurate in controls, but overestimated the clearance in RA patients. The degree of overestimation was not related to patient characteristics. Uncritical use of these equations in RA patients may lead to serious error.

Adult↗

Lack of evidence for the presence of neutrophil autoantibodies in the serum of patients with Felty's syndrome.

Sera of 22 patients with Felty's syndrome and 14 patients with rheumatoid arthritis were tested in assays routinely used for the detection of neutrophil antibodies (i.e. immunofluorescence, agglutination and cytotoxicity tests) as well as in the antibody-dependent lymphocyte-mediated granulocytotoxicity test. One or more of the routinely used assays were positive in a high percentage of the sera (77% and 64%, respectively). The antibody-dependent lymphocyte-mediated granulocytotoxicity test was only positive with sera of three patients with Felty's syndrome. Positive results in the immunofluorescence and agglutination tests could be attributed to the presence of immune complexes in the sera, whereas positive antibody-dependent lymphocyte-mediated granulocytotoxicity tests were probably due to the presence of HLA alloantibodies. It is concluded that serological tests routinely used for the detection of neutrophil autoantibodies should be interpreted with caution in patients with Felty's syndrome. Our results also indicate that the neutropenia in Felty's syndrome is rarely, if ever, due to neutrophil-specific autoantibodies.

Arthritis, Rheumatoid↗

The spleen in Felty's syndrome: a histological, morphometrical, and immunohistochemical study.

A histological study employing morphometrical and immunohistochemical methods was performed in 3 spleens removed because of Felty's syndrome (FS). A comparison was made with control spleens and with spleens removed from patients with idiopathic thrombocytopenic purpura (ITP) or autoimmune hemolytic anemia (AIHA). In FS, the spleen is enlarged, mainly due to expansion of the red pulp. The sinuses are enlarged, too, and contain many macrophages. 2 of our specimens showed many hyperplastic germinal centers; the 3rd contained no germinal centers. Only in the former cases did splenectomy lead to an increase in the number of circulating granulocytes. Immunohistologically, FS spleens differed from the control, the ITP, and the AIHA spleens. The results have provided further evidence indicating that the pathogenesis of granulocytopenia in FS differs from that of autoimmune hematocytopenias, and have given rise to the hypothesis that, in FS, the spleen is the site of interaction between immune complexes and granulocytes.

Anemia, Hemolytic, Autoimmune↗

IgA containing immune complexes and hematuria in ankylosing spondylitis. A prospective longitudinal study.

The occurrence of circulating immune complexes containing IgA (IgA-IC) was studied in groups of patients with ankylosing spondylitis (AS) selected for the presence or absence of hematuria. In studies done with 4 kinds of assays, IgA-IC were found more frequently and in higher titers in the 18 patients with AS with hematuria than in the 40 patients with AS without hematuria. Comparison of clinical indices of disease activity in these patient groups showed that the disease was more active in patients with AS with hematuria. Our findings confirm those made in a previous retrospective study on the relation between hematuria and circulating IgA-IC in AS and suggest that circulating IgA-IC play a role in the pathogenesis of hematuria in AS.

Adult↗

Abnormal clearance of soluble aggregates of human immunoglobulin G in patients with systemic lupus erythematosus.

In the present study, we tested mononuclear phagocyte system function in nine healthy controls and 15 SLE patients with complement activating 123I-labelled aggregates of human IgG (AIgG). Clearance half-time of AIgG was 26 +/- 8 min in controls, compared to 58 +/- 27 min in patients (P less than 0.005). Binding of AIgG to erythrocytes was significantly lower in patients, 9.3 +/- 8.1 vs 24 +/- 20% (P less than 0.05). The increase of C3a-levels in plasma was significantly lower in patients than in controls (P less than 0.05 at 3 and 8 min), suggesting less complement activation. Liver and spleen uptake of 123I-AIgG was measured with a gamma camera and expressed as liver/spleen uptake ratios. In patients, the liver/spleen uptake ratios were significantly higher than in controls at 15 min, 3.8 +/- 2.0 vs 2.31 +/- 0.7 (P less than 0.05), due to less splenic uptake of AIgG. Correlations between clearance half-time or liver/spleen uptake ratios and immune complex levels or disease activity were not found. This study indicates that clearance of soluble AIgG is abnormal in patients with SLE, due to decreased splenic uptake of AIgG.

Adult↗

Ectopic production of 1,25-dihydroxyvitamin D by B-cell lymphoma as a cause of hypercalcemia.

A patient with long-standing rheumatoid arthritis developed hypercalcemia (3.13 mmol/l) and was subsequently found to have a B-cell lymphoma (centroblastic type). The hypercalcemia was associated with high circulating concentrations of 1,25-dihydroxyvitamin D (235 pmol/l) and both abnormalities were corrected with treatment. A lymph node was excised before treatment and was incubated in vitro with either labeled or unlabeled 25-hydroxyvitamin D3. After purification of the extract and chromatography on three different HPLC systems, material comigrating with authentic 1,25-dihydroxyvitamin D3 was identified. This was shown to bind to a specific chick intestinal cytosol receptor and to dilute in parallel with synthetic 1,25-dihydroxyvitamin D3 in the receptor binding assay. In conclusion, hypercalcemia in malignant B-cell lymphoma can be due to extrarenal production of 1,25-dihydroxyvitamin D by lymphomatous tissue.

Arthritis, Rheumatoid↗

Magnetic resonance imaging in the evaluation of patients with rheumatoid arthritis and subluxations of the cervical spine.

We used magnetic resonance imaging (MRI) to examine 21 patients with rheumatoid arthritis and vertebral subluxations of the cervical spine, in whom neurologic symptoms and signs indicated spinal cord compression. Based on neurologic signs, the patients were assigned to 1 of 3 classes: class I, no objective signs of cervical myelopathy (9 patients); class II, only 1 objective sign of cervical myelopathy (4 patients); or class III, 2 or more objective signs of cervical myelopathy (8 patients). Atlantoaxial subluxation (20 patients) and subluxations below C2 (6 patients) were detected equally well by MRI and radiography. MRI revealed physical distortion of the spinal cord in all class III patients with compressive myelopathy. This distortion was found less frequently in class II and class I patients (3 patients), and the difference was statistically significant (P less than 0.005, class III versus class I and class II). No correlation was found between the vertebral dislocation (measured in millimeters) on plain radiographs and the presence of cord distortion on MRI. Myelography in class III patients showed that passage of contrast medium was blocked at the same level as the cord distortion seen on MRI. These findings suggest that MRI can serve as a useful, noninvasive procedure in the diagnosis and management of rheumatoid arthritis patients in whom compressive cervical myelopathy is suspected.

Aged↗

Rheumatoid arthritis with vertical atlanto-axial subluxation complicated by hydrocephalus.

The present report describes a patient with rheumatoid arthritis and vertical atlanto-axial subluxation who developed hydrocephalus with high intraventricular pressure and neuropsychiatric abnormalities. The vertical atlanto-axial subluxation and hydrocephalus were visualized by magnetic resonance imaging, which clearly demonstrated the basilar impression by the dens and ventricular enlargement. The patient recovered completely after ventriculo-cardial drainage.

Arthritis, Rheumatoid↗

Renal findings in rheumatoid arthritis: clinical aspects of 132 necropsies.

Renal abnormalities in 132 necropsied patients with rheumatoid arthritis were studied. Clinical findings before death included extra-articular manifestations of the disease (86% of patients), systemic vasculitis (6%), and uraemia (23%). Necropsy findings included nephrosclerosis (90%), systemic vasculitis (14%) with kidney involvement in 8%, amyloidosis (11%), membranous glomerulopathy (8%), and focal glomerular disease (8%). Association with clinical data suggests that both rheumatoid and non-rheumatoid disease may play a part in the cause of these abnormalities.

Adult↗

Elastase and collagenase activities in synovial fluid of patients with arthritis.

The activity of elastase and collagenase was measured in the synovial fluid (SF) of 24 patients with inflammatory and 6 patients with traumatic joint effusions. The enzyme activity was compared with local and systemic variables of the disease. Elastase and collagenase activity could be detected in 79 and 83%, respectively, of the arthritic SF, whereas no enzyme activity was found in the traumatic joint effusions. The SF enzyme activity showed no correlation with clinical, laboratory or radiographic variables of arthritis in the joint from which the fluid was obtained. Our results show that proteolytic enzyme activity in SF may help to distinguish inflammatory from noninflammatory joint effusions but does not reflect the severity of the arthritic process.

Arthritis↗