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Biomedical subjects

G Verbruggen

Publications and source records attributed to G Verbruggen.

At least 91 records · Page 5Linked to original sources

Immunoregulatory changes in autoimmune disease.

Peripheral blood T cell subpopulations were determined in patients with various rheumatic diseases [rheumatoid arthritis (RA); ankylosing spondylitis (AS); reactive synovitis (RS)]. No significant variation in OKT3+ cells was found among these groups. In RA, an increased percentage of OKT4+ was found in relation to the control group. For the other groups no difference was observed. In RA, a decreased percentage of OKT8+ cells was observed. Thus, the immunologic imbalance found in RA was not encountered in AS and RS although these disease--as well as the other pathologic disorders--are characterized by serum hypergammaglobulinemia. Furthermore, the decreased number of T suppressor cells found in peripheral blood of patients with active RA was not observed in their synovial fluid. Therefore we propose a failure of localization mechanism of T suppressor-cytotoxic lymphocytes in the synovial membrane of RA. Single doses of prednisolone produced a temporary decrease in peripheral blood total lymphocytes, T cells, T helper-inducer cells, and a less marked decrease in T suppressor-cytotoxic cells, in effect, a normalization of the immune balance, characterized by a decreased T helper/T suppressor ratio. In a similar fashion, patients receiving long-term levamisole exhibited a decrease in total lymphocytes, T lymphocytes, T helper cells, and T suppressor cells 6 and 24 hr after drug intake with a subsequent normalization of the OKT4+/OKT8+ ratio.

Adult↗

Peripheral blood T lymphocytes subpopulations in HLA-B7 related rheumatic diseases: ankylosing spondylitis and reactive synovitis.

The etiology of B lymphocyte hyperactivity in ankylosing spondylitis (AS) and in reactive synovitis is unknown and data available on the cellular immune system are controversial. We therefore evaluated peripheral blood T cell populations in AS patients and patients with reactive synovitis (RS) using monoclonal antibodies, previously shown to react with all T cells (OKT3), the inducer-helper T cell subset (OKT4) and the suppressor-cytotoxic T cell subset (OKT8). Results were compared with a normal control group and a group of rheumatoid arthritis (RA) patients. In AS an increase of OKT4+ cells was found, but the total number of T helper-inducer cells in peripheral blood was not different from the normal group and the group of patients with RS. Contrary to the results found in RA, where the helper-inducer/suppressor-cytotoxic ratio (OKT4+/OKT8+) was significantly increased, the immunoregulatory ratio in AS and in RS was normal suggesting another mechanism leading to B cell hyperactivity than in RA.

Adult↗

The effect of low doses of prednisolone on the traffic of T helper-inducer cells in rheumatoid arthritis.

The effects of a single dose of 5 and 10 mg of prednisolone on the kinetics of lymphocytes and T lymphocyte subsets were investigated in patients suffering from active rheumatoid arthritis. Six hours after intake of 10 mg of the drug a significant drop in total lymphocyte count, total T-cell numbers and T-helper cell numbers was recorded. The values returned to baseline values within 24 hours. Intake of 5 mg of prednisolone depressed total T-cell count and more particularly the absolute numbers of T-helper cells. No statistically significant changes occurred in T suppressor-cytotoxic cell traffics. The influence on the kinetics of T-helper cells was responsible for a significant decrease of helper/suppressor ratios in the intravascular compartment.

Arthritis, Rheumatoid↗

Long-term functional results of the non-surgical treatment of common bacterial infections of joints.

Thirty patients with acute bacterial infection of a peripheral joint were treated with intravenous antibiotics, daily closed needle aspiration and early mobilization therapy. Joint mobility, expressed as a percentage of normal mobility, was evaluated at the end of the reconvalescence period and again after 42 to 65 months (mean: 50 months). The functional outcome was excellent and joint mobility normal in 2/3 of the cases as revealed by the short- and long-term evaluation results. Factors that affected joint mobility were: delayed treatment, joint disorders prior to treatment, and ease of access to the joint for needle aspiration. Poor results were found in the presence of hip infections. In the long term, deterioration of joint mobility can occur in the same aggravating conditions. Treatment of septic arthritis with daily needle aspiration and early mobilization gave very good functional results.

Anti-Bacterial Agents↗

Comparison of serum salicylate levels and gastro-intestinal blood loss between salsalate (Disalcid)and other forms of salicylates.

In a first stage the effect of a single dose of 3 g of salsalate on serum salicylate level was compared with a single intake of 3 g of soluble or enteric-coated acetylsalicylates in 12 healthy subjects. Salsalate seems to resorb faster than the enteric-coated forms but more slowly than the soluble forms of acetylsalicylate. However, in comparison with these latter forms, salsalate activity is more protracted. In the second part of the study, 42 patients were admitted to a trial in which 3 to 5 g of salsalate was given daily and in which serum salicylate levels and blood loss in stools were measured using the method of labelling red blood cells with Cr51. The ideal dosage to obtain a serum salicylate level of 20 mg/100 ml seems to lie between 3 and 4 g of salsalate a day. Salsalate caused abnormal gastro-intestinal blood loss in only 2 of the 42 patients studied, which is significantly fewer compared with the soluble, intravenous or enteric-coated forms of acetylsalicylates.

Aspirin↗

HLA and juvenile chronic polyarthritis.

HLA antigens were determined in 38 patients with juvenile chronic polyarthritis (JCP) and in 1,000 normal controls. The incidence of the antigen B27 in JCP (55.3 per cent) was higher than in the controls (6.7 per cent). Patients with JCP could be further subdivided into four groups: (1) JCP evolving to ankylosing spondylitis (AS) (N = 3); (2) JCP with sacroiliitis (SI) (N = 18); (3) JCP without SI (N = 10); and (4) juvenile rheumatoid arthritis (JRA) characterized by positive seroloty (N = 7). Groups 1 and 2 had a high incidence of B27 (20/21), as contrasted to groups 3 and 4 (1/17). The sex distribution in groups 1 and 2 was similar to that found in AS in adults, whereas in groups 3 and 4 it was similar to that found in rheumatoid arthritis in adults. It is concluded that if B27 positives develop JCP, they also have a high risk of developing SI and acute uveitis. The authors propose using the term Still's disease for the overall group of children presenting with JCP before the age of 16 years. Subsequent follow-up permits classification into juvenile AS, JCP with SI, JCP without SI, or as JRA.

Adolescent↗

N-acetyl-beta-D-hexosaminidase system in synovial fluid.

The present study was undertaken with the object of examining the N-Acetyl-beta-D-hexosaminidase activity in joint effusions from non-inflammatory (osteoarthrosis) and inflammatory (rheumatoid arthritis, gouty arthritis and chondrocalcinosis) joint diseases. The biochemical properties of four purified molecular forms were investigated. They were separated on the basis of their net charge, using DEAE-cellulose anion-exchangers. In the order of their outcome from the anion exchanger the four enzymes (B, I1, I2 and A) were found to have pH optima at 4.5-4.75, 4.20, 4.00 and 4.75, respectively. The first three enzymes proved to be heat-stable and the fourth enzyme fraction was a heat-labile form. By means of gel-filtration techniques, the enzymes were eluted into two fractions. The first contained the thermolabile A form and the molecular weight of this enzyme was estimated at 162000. The second fraction included the three thermostable enzymes. Their molecular weight was estimated at 135000. As described by Ikonne & Ellis (6) the hexosaminidase A from sera was less tightly held by the anion-exchanger than was the hexosaminidase A from tissues (polymorphonuclear cells, synovial membrane tissue, cartilage). Thus the serum type (As) must be distinct from the tissue type (At). The activity of the tissue type probably originating from the leukocytes and from the synovial membrane was more pronounced in the synovial effusions of the patients with inflammatory joint diseases. The hexosaminidase A fraction from synovial fluids of patients with osteoarthrosis contained only the serum type of enzyme.

Arthritis, Rheumatoid↗

N-acetyl-beta-d-glucosaminidase activity in synovial fluid.

N-acetyl-beta-D-glucosaminidase activity in the synovial fluid of different articular diseases was studied and statistical investigations were carried out after logarithmic transformation of the data. The enzyme activity in the synovial fluid of rheumatoid arthritis is increased when compared with osteoarthrosis and traumatic effusions. The enzyme activity in traumatic effusions is also increased in comparison with osteoarthrosis. A linear relation was found between the enzyme activity in cell-free fluid and the polymorphonuclear leucocyte (PMN) count in rheumatoid arthritis osteoarthrosis and in miscellaneous synovitis. The activity per PMN cell was determined and found to be relatively constant in the synovial fluid of inflammatory diseases (rheumatoid arthritis, chondrocalcinosis, miscellaneous synovitis). The N-acetyl-beta-D-glucosaminidase activity per PMN cell in serum was found to be significantly lower than in synovial fluid.

Arthritis, Rheumatoid↗

Hand radiology characteristics of patients carrying the T(303)M mutation in the gene for matrilin-3.

OBJECTIVE: To determine whether the recently described hand osteoarthritis (HOA)-associated T(303)M mutation in the gene for matrilin-3 (MATN3) is associated with specific radiological changes on hand radiographs. METHOD: Standard hand radiographs from 26 HOA patients carrying the T(303)M missense mutation in the MATN3 gene (T(303)M patients) were compared with those from 52 HOA controls matched for sex, age, and clinical disease severity. Two blinded readers scored the radiographs, using the Verbruggen-Veys anatomical scoring system for the interphalangeal and metacarpophalangeal joints and the OARSI atlas scoring system for the first carpometacarpal (CMC1) joints. A scoring system based on the latter was used for the scaphoid-trapezoid-trapezoideum (STT) joints. RESULTS: No particular distinguishing features were found in the T(303)M patients and the prevalence of erosive and cystic changes was similar to the control group. As a group, however, the T(303)M patients had more severe thumb-base affection, particularly in the STT joint. Thus, definite radiological OA in both CMC1 and STT joints and higher STT scores compared with CMC1 were significantly more common in patients carrying the T(303)M mutation. Radiological scores for joint-space narrowing (CMC1 and STT) and osteophytes (STT) were also significantly higher in the T(303)M patients. CONCLUSION: Patients carrying the T(303)M mutation in the gene for matrilin-3 express a form of HOA that is radiologically indistinguishable from idiopathic HOA in individual patients but they have more severe thumb-base involvement, particularly in the STT joint. This is the first described genetic mutation that is associated with a common form of osteoarthritis.

Adult↗

Broadening of the T cell receptor spectrum among rheumatoid arthritis synovial cell-lines in relation to disease duration.

OBJECTIVE: The aim of the study was to evaluate the T cell receptor (TCR) family usage in T cell-lines from subcutaneous nodules and synovium from patients with rheumatoid arthritis (RA), with specific reference to the duration of symptoms. In vitro adherence characteristics of nodular T cells was studied as well. METHODS: Monoclonal antibodies were used to determine the distribution of TCR families in T cell-lines from synovium of patients with early and long-standing RA, from rheumatoid nodules and control tissues. An in vitro binding assay with T cell-lines from 2 rheumatoid nodules was performed. RESULTS: In early RA synovium, a restricted TCR family usage was observed in 5 out of 8 patients, contrary to long-standing disease, peripheral blood, ileum and colon. In RA nodules, a similar degree of restriction was noted. Moreover, the same TCR family was overexpressed by T cell-lines from different nodules derived from the same patient. T cell-lines from rheumatoid nodules demonstrated a preferential in vitro adherence to rheumatoid synovium and rheumatoid nodules, while no binding was observed on skin or tonsil. CONCLUSION: The TCR spectrum among RA synovial cell-lines broadens in relation to the disease duration. The overexpression of the same TCR family in different rheumatoid nodules from the same patients, and the in vitro adherence of T cell-lines from rheumatoid nodules may be indicative for recirculation between the different disease manifestations in RA.

Adult↗

The influence of hydrocortisone on aggrecan metabolism in human articular chondrocyte cultures: comparison of two different matrices.

OBJECTIVE: Numerous reports of negative effects as well as protective effects of glucocorticoids on articular cartilage convinced us to study the influence of hydrocortisone on aggrecan synthesis of isolated phenotypically stable human articular chondrocytes cultured in two different matrices. METHODS: Macroscopically normal human articular cartilage was obtained from femoral condyles within 24 hours postmortem. Chondrocytes were isolated and cultured in gelled agarose or in alginate. After 14 days in culture, hydrocortisone was added for 5 days at concentrations ranging from 0.005 microgram to 1 mg/ml for the agarose cultures and from 0.005 microgram to 1 microgram/ml for the alginate culture system. Aggrecan synthesis was measured by the incorporation of 35Sulphate, and the proportion of neosynthesized aggrecan that bound to hyaluronan to form aggrecan aggregates was analyzed by gel chromatography. RESULTS: At concentrations from 0.005 to 1 microgram/ml, hydrocortisone was found to produce a similar dose-dependent stimulation of aggrecan synthesis in both matrices. The synthesis of aggrecans remained at the same level for concentrations of 1 microgram/ml up to 100 micrograms/ml of hydrocortisone. When supraphysiological concentrations of hydrocortisone were added the aggrecan synthesis rate plateau declined. Simultaneously with the increase in aggrecan synthesis, the proportion of low-molecular weight 35S-proteoglycans decreased in favour of 35S-aggrecan aggregates and monomers in the agarose system. The chondrocytes cultured in alginate showed this increase of aggrecan aggregates and monomeric aggrecans in both the cell-associated and the inter-territorial matrix. CONCLUSION: Hydrocortisone is a stimulator of aggrecan synthesis by normal human articular chondrocytes cultured in vitro. The two culture systems (agarose and alginate) tested in this experiment showed a comparable aggrecan synthesis rate, increasing under the influence of hydrocortisone at concentrations up to 1 microgram/ml. The proportions of 35Sulphate incorporated in aggrecan aggregates and monomeric aggrecan were also higher under the influence of hydrocortisone.

Aggrecans↗