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Biomedical subjects

G Verbruggen

Publications and source records attributed to G Verbruggen.

At least 109 records · Page 6Linked to original sources
PubMedDate not supplied

Gut mucosal T cell lines from ankylosing spondylitis patients are enriched with alphaEbeta7 integrin.

OBJECTIVE: An intriguing link between gut and synovial inflammation exists in patients with spondyloarthropathy (SpA), illustrated by the high frequency of microscopically inflammatory gut lesions observed in these patients. We hypothesise that aberrant homing of mucosal T cells might play a role in the induction/perpetuation of arthritis in SpA. Here, we analyse the expression of the homing molecules alpha4beta7 and alphaEbeta7 on mucosal T cells from patients with ankylosing spondylitis (AS) and controls, in view of the critical role of these receptors in the homing of mucosal lymphocytes. METHODS: Colonic biopsy specimens were obtained from patients with AS (n = 23) and controls (n = 30). Biopsy specimens were immunostained, treated for extraction of intraepithelial lymphocytes (IEL) and lamina propria lymphocytes (LPL) or cultured in the presence of IL-2. The expression of the beta7 integrins was investigated. RESULTS: In situ no differences were observed in alphaEbeta7 and alpha4beta7 integrin expression in isolated IEL and LPL, whether determined by flow cytometry or by immunohistochemical staining. In gut mucosal T cell lines, alphaEbeta7 expression was significantly higher in the mucosa of patients with AS compared with controls. Alpha4beta7 was highly expressed on T cells in both groups studied. Mucosal T cells either expressed only the alpha4beta7 integrin or co-expressed the alpha4beta7 and alphaEbeta7 integrins. Almost none of them expressed only the alphaEbeta7 integrin. CONCLUSION: In gut mucosal T cell lines from patients with AS an increased expression of alphaEbeta7 was observed.

Adolescent↗
PubMedDate not supplied

Influence of polysulphated polysaccharides and hydrocortisone on the extracellular matrix metabolism of human articular chondrocytes in vitro.

OBJECTIVE: To evaluate the influence of hydrocortisone and two polysulphated polysaccharides (xylosan polysulphate and chondroitin polysulphate) on the extracellular matrix metabolism of chondrocytes cultured in gelled agarose. METHODS: Isolated chondrocytes from normal femoral cartilage of the knee joints of 7 donors were cultured in gelled agarose to maintain their differentiated phenotype. After two weeks of culture, hydrocortisone (0.2 microgram/ml), xylosan polysulphate (10 micrograms/ml) and chondroitin polysulphate (10 micrograms/ml) were added to the culture media supplemented with or without interleukin (IL)-1 beta. After one week of incubation, the cells were liberated from the agarose with agarase. Isolated cells were labelled with antibodies against aggrecan and type II collagen, as well as biotinylated hyaluronic acid binding protein to analyse the extracellular matrix (ECM) molecules in the cell-associated matrix (CAM). The levels of matrix metalloproteinase (MMP)-1, -3, and -13, as well as tissue inhibitor of metalloproteinase (TIMP)-1 and -3 were determined after the cells had been permeabilised and stained with the appropriate antibodies. Triplicate samples were analysed with flow cytometry. RESULTS: IL-1 beta decreased the accumulation of aggrecan, hyaluronan and type II collagen in the CAM and increased intracellular MMP-1, -3 and -13 at a concentration of 100 pg/ml. Xylosan polysulphate and chrondroitin polysulphate restored the expression of these CAM molecules in these IL-1 beta-treated cultures. Hydrocortisone stimulated the accumulation of CAM aggrecan and hyaluronan whether or not under the exposure to IL-1 beta. Intracellular MMP-1, -3, -13 and TIMP-1 and -3 of IL-1 beta-treated cells was downregulated after treatment with hydrocortisone. CONCLUSION: Both hydrocortisone and the two polysulphated polysaccharides could stimulate the accumulation of CAM macromolecules of IL-1 beta-treated chondrocytes. This effect probably resulted in part from the downregulation of MMPs. These agents showed cartilage structure modifying effects in vitro.

Adult↗
PubMedDate not supplied

Intra-articular injection pentosanpolysulphate results in increased hyaluronan molecular weight in joint fluid.

The influence of an oversulphated glycosaminoglycan, pentosanpolysulphate, on hyaluronan metabolism of the synovial lining cell was studied in vivo in human volunteers. Significant increases in the mean degree of polymerisation of the hyaluronan chains were observed after a series of four to six intra-articular injections of this glycosaminoglycan. No increases in hyaluronan synthesis rates were observed. Repeated administration of the drug did not cause any inflammation or bleeding in the joint cavity.

Humans↗
PubMedDate not supplied

Influence of human recombinant interleukin-1 beta on human articular cartilage. Mitotic activity and proteoglycan metabolism.

The effects of human recombinant interleukin-1 beta (IL-1 beta) were investigated on recently isolated (1 to 3 weeks) and on well-established (older than 3 weeks) monolayer cultured human articular chondrocytes. IL-1 beta was found to depress 35S-proteoglycan synthesis rates and to enhance prostaglandin E2 (PGE2) production in these monolayer cultured chondrocytes. Induction of 35S-proteoglycan-degradative activity by these cells also occurred in IL-1 beta treated cultures. These "catabolin" -IL-1 activities were observed in recently isolated as well as in well-established "old" cultures. IL-1 beta increased 3H-thymidine incorporation rates in the "old" cultures. However, in recently isolated chondrocytes a dose-dependent reduction of the 3H-thymidine incorporation occurred. The depression of mitotic activity in these cells was partially abolished by indomethacin, indicating that this depression was a PGE2 effect. However, supplementing IL-1 beta with indomethacin did not raise the 3H-thymidine incorporation rates above the control levels. It can be concluded that IL-1 beta in itself is unable to induce proliferation in recently isolated cartilage cells. Our results suggest the possible existence of two different receptors for the different IL-1 beta activities. Hence, human articular chondrocytes respond differently to in vitro IL-1 beta exposure at different stages of differentiation.

Cartilage, Articular↗
PubMedDate not supplied

The synthesis and immobilisation of cartilage-specific proteoglycan by human chondrocytes in different concentrations of agarose.

Chondrocytes were cultured in agarose gels of different concentrations. In this in vitro model these cells synthesize tissue-specific proteoglycans. The rate of proteoglycan synthesis was not dependent on the concentration of the surrounding gel. The immobilisation of these macromolecules in monomeric and in aggregated form were studied. 0.5% to 1.0% of agarose failed to retain important amounts of proteoglycan. Proteoglycan monomers and even aggregates diffused to the incubation medium. 2.0% and 4.0% of agarose immobilised the bulk of the aggregates and approximately 50% of the monomeric proteoglycans. Low-molecular proteoglycan species or break-down products freely moved out of the gel. The reproducibility of the variables concerning proteoglycan metabolism was very good.

Carbon Radioisotopes↗
PubMedDate not supplied

Proteoglycan metabolism in isolated chondrocytes from human cartilage and in short-term tissue-cultured human articular cartilage.

The effect of piroxicam on proteoglycan metabolism of human cartilage cells was investigated in two in vitro models. Cells or tissue samples were obtained from six different donors. Piroxicam levels used in the test systems ranged from 2 to 6 micrograms r/ml and were comparable with serum concentrations in humans after oral intake. Piroxicam increased the synthesis rates of proteoglycan in some batches of isolated and monolayer-cultured chondrocytes and in tissue-cultured articular cartilage. The fact that this increase in the synthesis of proteoglycan was restricted to some of the donors whereas isolated cells or tissue samples from other individuals remained unaffected illustrates the heterogeneity of different human donors. Depression of proteoglycan synthesis in the presence of the drug was not observed.

Cartilage↗
PubMedDate not supplied

Salicylate-induced gastrointestinal bleeding: comparison between soluble buffered, enteric-coated, and intravenous administration.

Serum salicylate levels and blood loss in stools were compared in 94 patients after intake of various forms of acetylsalicylate. Four different oral soluble forms, an enteric-coated variety and an intravenous form were evaluated. Analysis of the results of blood loss measurement in stools showed that salicylate users could be divided into "bleeders" and "non-bleeders". Administration of enteric-coated and intravenous forms of salicylates showed less blood less than ingestion of soluble forms. Only after administration of enteric-coated or intravenous forms of salicylates was a relationship between serum salicylate level and blood loss in stools observed in "bleeders". This suggests a similar mode of action of both these preparations on gastric mucosa. We conclude that enteric-coated forms of salicylates cause gastrointestinal bleeding by a systemic action on gastric mucosa.

Aspirin↗
PubMedDate not supplied

Reparative response of human articular cartilage in tissue culture. Comparison between a normal and an osteoarthritic knee of the same donor.

Some evidence is presented that the metabolism of visually intact cartilage taken from a knee with focal osteoarthritic lesions, may already be affected. Proteoglycan metabolism of articular cartilage from the macroscopically unaffected right knee and the osteoarthritic left knee of the same donor was assayed in long-term tissue culture. A good reparative response was found in the right knee with an increase in the relative amount of radiolabelled proteoglycan and proteoglycan aggregates, and in the total amount of labelled proteoglycan per mg dry tissue. No significant differences were found when the anteromedial, anterolateral and posterolateral areas were compared. Visually intact samples taken from the left knee, with a deep osteoarthritic cartilage erosion on the medial condyle, showed no accumulation of radiolabel into proteoglycan and proteoglycan aggregates for the enzymatically pretreated samples. This was interpreted as a repair failure.

Cartilage, Articular↗
PubMedDate not supplied

Goldsalts, levamisole and D-penicillamine as first choice slow-acting antirheumatic drugs in rheumatoid arthritis--a long-term follow-up study.

In the present study, 345 rheumatoid arthritis patients were treated using goldsalts, D-Penicillamine or levamisole as the slow-acting antirheumatic drug of first choice. Goldsalts were given to 182 patients, levamisole to 139 and D-Penicillamine to 24. At the time of the present evaluation, 83 patients were still on goldsalts (44.6%), 63 on levamisole (45.2%) and 11 on D-Penicillamine (45.9%). Adverse reactions required interruption of treatment in 64 patients on goldsalts (35.2%), in 44 on levamisole (31.7%) and in 5 on D-Penicillamine (20.8%). Inefficacy was responsible for withdrawal of 33 patients receiving goldsalts (18.1%), 30 receiving levamisole (21.6%) and 8 receiving D-Penicillamine (33.3%). The duration of treatment was 4.6 years for goldsalts, 3.6 years for levamisole and 3.6 years for D-Penicillamine. In the present analysis none of the compounds was found to have a definite advantage over the others. The rather favourable treatment continuation rates in this study can be attributed to the fact that the slow-acting antirheumatic drugs were given at an early stage of the disease, preferably before the occurrence of radiological lesions.

Adult↗
PubMedDate not supplied

Evaluation of T cell subsets with monoclonal antibodies in synovial fluid in rheumatoid arthritis.

Monoclonal antibodies that react with all T cells (OKT3), the inducer-helper T cell subset (OKT4), and the suppressor-cytotoxic T cell subset (OKT8) have been used to evaluate T cell and T cell subpopulations in synovial fluid (SF) from patients with rheumatoid arthritis (RA). We found that the immunoregulatory ratio of SF lymphocytes ranged from normal values to extremely low values indicating normal to excess numbers of OKT8+ cells. The rheumatoid synovium in patients with RA is characterized by the presence of lymphoid aggregates in which HLA-DR+ interdigitating cells form close contacts with a large number of OKT4+ T cells, while the OKT8+ T cells are sparse. It may be that the localizing mechanisms for OKT8+ suppressor cells in lymphoid aggregates are deficient in RA and the cells are thus permitted to pass into synovial exudates, resulting in an increase of OKT8+ cells in the SF.

Adult↗
PubMedDate not supplied

Levamisole as basic treatment of rheumatoid arthritis: longterm evaluation.

We evaluated longterm levamisole treatment of 201 rheumatoid patients. Fifty-nine patients in their 1st yr of treatment were not analyzed; of the remaining 142, 69 (49%) still took levamisole with benefit. Levamisole was stopped in 32 patients (22%) for inefficacy and for reversible adverse reactions in 37 (26%). Leukotoxic side-effects were the commonest cause of withdrawal (23 patients = 16%). Since June 1977, we administer levamisole on a 1 d/wk schedule (150 mg), with determination of white blood cells 10 h after intake to detect high-risk patients for agranulocytosis. With disease exacerbation during treatment or lack of response after 6 months, the drug is given on a 2nd non-consecutive day. Since June 1977, cases of agranulocytosis have not been observed. Allergic vasculitis did not occur with a 1 d/wk schedule. The absence of nephrotoxicity and hepatotoxicity is stressed. Only 4 patients (3%) were lost to follow-up. Comparison is made with longterm use of gold and D-penicillamine. We conclude that levamisole is a useful slow acting antirheumatic drug.

Agranulocytosis↗
PubMedDate not supplied

Detection and identification of antinuclear autoantibodies in the serum of normal blood donors.

The occurrence of antinuclear antibodies (ANA) in the serum of 485 healthy volunteer blood donors was assessed. Sixty two sera displayed nuclear immunofluorescence staining on Hep-2 cells using a polyvalent anti-Ig conjugate. In general, the titer of these antibodies was low (42/62 sera displaying a titer lower than or equal to 1:80). In only 23 sera were the ANA of the IgG isotype, which is the more disease-related immunoglobulin class of autoantibodies. In order to define the frequency of antibodies to extractable nuclear antigens and dsDNA within this population, sera were further analyzed by counterimmunoelectrophoresis. Western blot and the Crithidia luciliae assay. One serum displayed weak antids DNA reactivity; another serum had anti-SSA/Ro activity. On Western blot several patterns were found. They could not be identified with any of the available reference antisera.

Adolescent↗