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Biomedical subjects

O Huber-Bruning

Publications and source records attributed to O Huber-Bruning.

At least 19 recordsLinked to original sources
PubMed1997

Decrease in peripheral type 1 over type 2 T cell cytokine production in patients with rheumatoid arthritis correlates with an increase in severity of disease.

OBJECTIVES: To compare peripheral type 1 (T1) and type 2 (T2) T cell activities in rheumatoid arthritis (RA) patients with that found for osteoarthritic (OA) patients and healthy controls and to correlate peripheral T1/T2 cell activity in RA with parameters of the disease. METHODS: Peripheral blood mononuclear cells were isolated from patients with RA (n = 66), OA (n = 19), and healthy controls (n = 15). Primary T cell activity in these mononuclear cells was enhanced by means of anti-CD3/anti-CD28, which mimicks stimulation of T cells by activation of the T cell receptor and a major co-stimulatory signal. Interferon gamma (IFN gamma) production and interleukin 4 (IL4) production in the three groups were quantified as measures of T1 and T2 cell activity, respectively, and compared. Serum tumour necrosis factor alpha (TNF alpha), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and joint destruction assessed radiographically of RA patients were determined as parameters of disease activity and correlated with T1/T2 cell activity. RESULTS: Peripheral T cells from RA patients produced significantly less IFN gamma and more IL4 than T cells from both age and sex matched OA patients and healthy controls. Moreover, in RA patients both a decrease in IFN gamma and an increase in IL4 production correlated with an increase in serum TNF alpha, ESR, CRP, and joint destruction. CONCLUSIONS: These results suggest a role for differential T cell activity in RA. In view of the intra-articular T1 cell predominance the results might be explained by selective T1 cell migration into the joint or peripheral suppression of T1 cell activity.

Aged↗
PubMed1996

Androgens as adjuvant treatment in postmenopausal female patients with rheumatoid arthritis.

OBJECTIVE: To examine the possible beneficial effect of androgens in postmenopausal women with active rheumatoid arthritis. METHODS: 107 women participated in a double blind placebo controlled trial to evaluate the effect of 50 mg testosterone propionate intramuscularly every two weeks for one year. RESULTS: An improvement in ESR, Dutch health assessment questionnaire, and pain was noted. In addition, 21% of patients treated with testosterone fulfilled the ACR improvement criteria after one year, versus only 4% of the placebo group. The treatment was well tolerated. CONCLUSIONS: Testosterone may improve the general wellbeing of postmenopausal women with active rheumatoid arthritis.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1994

Changes in proteoglycans of ageing and osteoarthritic human articular cartilage: an electron microscopic study with polyethyleneimine.

BACKGROUND: Ageing and osteoarthritic (OA) cartilage show characteristic alterations in chondrocyte morphology and in the composition and content of matrix proteoglycans (PGs). Data concerning matrix components are mostly of biochemical nature. Ultrastructural histochemistry is needed to gain more information about distribution of these altered matrix components. METHODS: We used the cationic dye polyethyleneimine (PEI) to visualize at the EM level alterations in the distribution and dimensions of PGs of human healthy young, healthy aged, and OA articular cartilage. RESULTS: Young cartilage contained PEI-positive granules in the superficial layer and big winding PEI-positive structures in the deeper layers. In the healthy aged tissue, PEI-positive granules were observed throughout the matrix and smaller winding structures were present in the deeper layer. In OA cartilage both types of PEI-positive structures were absent in the superficial layer. Deeper in the matrix PEI-positive granules could be demonstrated. Moreover, PEI-positive angular structures were observed in the deeper zones. CONCLUSIONS: The differences in PEI-positive structures are a good reflection of the differences in PGs between young, ageing, and OA cartilage as demonstrated in biochemical studies. PEI, used at the EM level, gave more precise information concerning the localized changes in quality, quantity, and location of PGs in articular cartilage during ageing and disease.

Aged↗
PubMed1994

Cytokines and proteoglycans.

Cytokines play an important regulatory role in the metabolism of proteoglycans. Proteoglycans are found in plasma membranes, but predominantly in the extra-cellular matrix. In the latter they are quantitatively and qualitatively essential components. Especially in a tissue like cartilage without any blood vessels, the cells are dependent on cytokines for the communication among themselves in the extra-cellular matrix and also for communication with the 'outside world'. Various cytokines have been found to be able to penetrate the extra-cellular matrix and inhibit, respectively stimulate the proteoglycan synthesis. Also, the degradation of proteoglycans can be stimulated, respectively inhibited by several cytokines. In addition, some cytokines have been found which regulate the effects of the other cytokines. With respect to proteoglycan metabolism a complex cytokine network is emerging. Furthermore it is becoming increasingly clear that proteoglycans are connected to the cytokine network by their own bioactive functions. First, they possibly possess cytokine activities themselves. Second, they can function as receptors, protectors, inactivators and storage ligands for cytokines. So the proteoglycans are clearly involved in the feedback signalling from the extra-cellular matrix to the cells that are synthesizing this extra-cellular matrix. Together with agonistic or antagonistic cytokines they are involved in the regulation of proteoglycan turnover during balanced or unbalanced metabolism in normal, respectively pathological situations.

Animals↗
PubMed1993

Osteoarthritic human cartilage is more sensitive to transforming growth factor beta than is normal cartilage.

Osteoarthritis is a degenerative joint disease, characterized by the destruction of the articular cartilage. One of the first changes in the osteoarthritic articular cartilage is a reduction in proteoglycan content. In this study we demonstrate that transforming growth factor beta (TGF beta), a multi-functional growth factor, stimulates the proteoglycan synthesis of explants from human articular knee cartilage dose-dependently in vitro. Osteoarthritic cartilage proved to be much more sensitive to stimulation by TGF beta than normal healthy cartilage. This may indicate that TGF beta plays an important role in the repair of osteoarthritic cartilage.

Aged↗
PubMed1993

Articular cartilage explant culture; an appropriate in vitro system to compare osteoarthritic and normal human cartilage.

Proteoglycan metabolism of normal and histologically mild to moderate osteoarthritic cartilage explants were studied. Explants were obtained from the human knee of donors aged over 40 years. Proteoglycan content, synthesis and release were very similar in normal cartilage obtained from donors with focal osteoarthritis and cartilage obtained from donors without any sign of osteoarthritis. This suggests that cartilage obtained from donors with focal osteoarthritis indeed can be considered as "normal". The relatively large surface area-compared to their natural setting in the joint- of cartilage explants in culture did not affect the parameters measured, as there was a strong linear correlation between these parameters and the weight of the explants. From our results, we conclude that the use of full depth cartilage tissue explants is a reliable way to assess and compare proteoglycan content, synthesis and release in normal and osteoarthritic cartilage from the same donor.

Adult↗
PubMed1992

Influence of rheumatoid synovial fluid and cells on proteoglycans in human cartilage explants. Modulation by piroxicam.

We have studied the effects of cell-free rheumatoid synovial fluid (RASF) and the conditioned medium (CM) from these cells on the proteoglycans (PGs) of normal human cartilage and the influence which piroxicam might have on these processes. Both RASF and the CM from RASF cells enhanced the PG release from the cartilage explants. The effects of the above mentioned fluids on the cartilage PG content depended on the metabolic state of the cartilage i.e. correlated inversely with the PG synthesis. Whether this was due to the presence of anabolic and catabolic factors in these fluids is discussed. Piroxicam had no adverse effect on the PGs of human cartilage in vitro. Piroxicam prevented the cartilage PG depletion when it was induced by the CM from RASF cells.

Adult↗
PubMed1992

Intermittent hydrostatic compressive force stimulates exclusively the proteoglycan synthesis of osteoarthritic human cartilage.

In paired observations the in vitro proteoglycan turnover was studied of human normal and osteoarthritic cartilage in the absence and presence of intermittent hydrostatic compressive force. Shortly after collection, osteoarthritic cartilage showed a higher proteoglycan synthesis rate than normal cartilage, whereas after culture the reverse was found. Exposure during culture to hydrostatic intermittent compression of a low physiological magnitude enhanced the proteoglycan synthesis rate for osteoarthritic cartilage, whereas normal was unaffected by this hydrostatic intermittent compression. This enhancing effect was reversible. We conclude that human osteoarthritic cartilage is in vivo synthetically more active than normal cartilage, but loses this increased activity in vitro. Enhanced sensitivity of osteoarthritic cartilage to compressive forces may contribute to the increased proteoglycan synthesis of osteoarthritic cartilage.

Adult↗
PubMed1992

Human osteoarthritic cartilage is synthetically more active but in culture less vital than normal cartilage.

The proteoglycan turnover of human osteoarthritic (OA) cartilage was compared to that of normal (N) cartilage. The cartilage was obtained postmortem from human femoral knee condyles. Short term cultures were compared to longterm cultures, and proteoglycan synthesis rate, content and release determined. Proteoglycan synthesis rate, determined shortly after collection of the cartilage, was higher in OA cartilage than in N cartilage. After longterm culture, the initially higher proteoglycan synthesis rate of OA cartilage became lower than that of N cartilage. An increased percentage release of proteoglycans from OA cartilage compared to N cartilage was apparent both shortly after collection of the cartilage and after culture. Thus, although OA cartilage in vivo is synthetically more active, in vitro it has an increased catabolic and a decreased anabolic activity, from which we conclude that OA cartilage is less vital than N cartilage.

Aged↗
PubMed1992

Local changes in proteoglycan synthesis during culture are different for normal and osteoarthritic cartilage.

Proteoglycan synthesis of mild-to-moderate osteoarthritic human knee cartilage was compared with that of normal cartilage of the same donor. Immediately after cartilage was obtained, the synthesis rate of proteoglycans was higher for osteoarthritic cartilage than for normal cartilage. Proteoglycan synthesis was then located, for both normal and osteoarthritic cartilage, in the middle and deep zone. However, after 4 days of culture, proteoglycan synthesis rate was higher for normal cartilage than for osteoarthritic cartilage. The reason for this transition from a lower to a higher proteoglycan synthesis rate was a strong increase in the proteoglycan synthesis in the superficial zone of normal cartilage. This was not observed for the osteoarthritic cartilage. The chondrocytes in the superficial zone of osteoarthritic cartilage, in contrast to normal cartilage, were mainly joined in cell clusters and proliferating. This may explain their inability to contribute to proteoglycan synthesis.

Aged↗
PubMed1991

In vitro influence of ketoprofen on the proteoglycan metabolism of human normal and osteoarthritis cartilage.

We investigated the influences of ketoprofen on the proteoglycan (PG) turnover of human articular cartilage explants in three groups: normal young with a high basal PG synthesis, normal adult and osteoarthritis cartilage, both with a low basal PG synthesis. Ketoprofen had no influence on the mean PG synthesis rate of normal adult and OA cartilage after 4 days of culture nor on the cartilage PG content after 8 days of culture. There was no relation between the histological grade of OA and effects of ketoprofen. In normal young cartilage ketoprofen induced an increase of the PG synthesis rate when added to the culture in a concentration of 10(-4) M. No correlation existed between the effect of ketoprofen and the basal PG synthesis of normal cartilage.

Adult↗
PubMed1991

Role of TNF alpha, in relation to IL-1 and IL-6 in the proteoglycan turnover of human articular cartilage.

In both young and old human articular cartilage explants, TNF alpha induced a concentration-dependent, reversible suppression of the proteoglycan (PG) synthesis. Young cartilage was more sensitive to TNF alpha than old cartilage: 50% suppression of PG synthesis was reached at a TNF alpha concentration of 5 U/ml for young and 30 U/ml for old cartilage, whereas at 10(3) U/ml the PG synthesis of young cartilage was blocked and that of old cartilage suppressed by 80%. These inhibition levels of PG synthesis resulted in 25% PG depletion of the explants after 8 days of culture. The release of cartilage PG was not enhanced. TNF alpha induced no detectable amounts of IL-1 (less than 0.01 U) in young or old cartilage but did induce IL-6 production. The induced amounts of IL-6 were higher in young than in old cartilage but no dose-dependency was evident. Antibodies to neither IL-1 nor IL-6 had any influence on the TNF alpha-induced suppression of PG synthesis. The combination of TNF alpha and IL-1 led to an additive inhibition of PG synthesis which had no relationship to induced IL-6. TNF alpha was about 100-fold less active than IL-1.

Aging↗
PubMed1991

No conclusive evidence of an epidemiological relation between Klebsiella and ankylosing spondylitis.

Fifty-six patients with ankylosing spondylitis and 87 healthy controls were screened for Klebsiella strains in their stools using a new highly sensitive culture medium. The presence of Klebsiella strains in the patient group was compared with activity of the disease. In a dynamic study changes in Klebsiella quantity over a period of 3 months were compared with changes in disease activity over the same period. The patient and control group showed similar percentages of Klebsiella carriage. In the patient group no temporal relation could be found between activity of the disease and the presence of Klebsiella in the intestinal tract.

Female↗
PubMed1991

Relation between patients' own health assessment and clinical and laboratory findings in rheumatoid arthritis.

Health status encompasses not only physical aspects, but also psychological and social aspects. A multidimensional health status questionnaire was used in 69 Dutch patients with rheumatoid arthritis to assess their physical, psychological and social well being. The same day clinical and laboratory data were recorded. The health status questionnaire provided additional information to clinical and laboratory findings. The various clinical and laboratory measures of disease activity reflect aspects other than the self-reported measure of physical well being. As such they are not interchangeable. Furthermore clinical and laboratory measures of physical well being appeared to be unrelated with psychological and social measures. In contrast, the patients' self-report of physical well being was related only with depressive mood and to some extent with anxiety.

Adult↗
PubMed1990

Interleukin-1-induced interleukin-6 is required for the inhibition of proteoglycan synthesis by interleukin-1 in human articular cartilage.

Cartilage from normal controls, patients with osteoarthritis, and patients with rheumatoid arthritis produced no interleukin-6 (IL-6) in culture. However, IL-1 induced massive production of IL-6 (up to 135 ng/ml) in cartilage from all 3 sources, in a dose-dependent manner (in some cases, a peak value was reached). The levels of induced IL-6 were similar to those found in rheumatoid arthritis synovial fluid. At IL-1 concentrations that induced almost complete inhibition of proteoglycan (PG) synthesis, IL-6 production could still be increased considerably. Exogenous IL-6 inhibited PG synthesis by up to 25%. IL-1-induced inhibition of PG synthesis was reversed by antibodies against recombinant human IL-6. These results suggest that IL-6 is required for the IL-1-induced inhibition of PG synthesis.

Adult↗
PubMed1990

Mycobacterial antigens stimulate rheumatoid mononuclear cells to cartilage proteoglycan depletion.

In a coculture with porcine articular cartilage explants unstimulated blood mononuclear cells (BMC) from patients with rheumatoid arthritis (RA), but not from healthy controls, induced proteoglycan depletion of dead cartilage. Specific stimulation of the RA BMC with Mycobacterium tuberculosis (MT), in comparison with concanavalin A (Con-A), strongly enhanced the proteoglycan depletion of living cartilage; this was not found with the BMC of healthy controls. However, the MT induced proliferative responses of the same BMC were similar in healthy controls and patients with RA. Neither the proliferative response nor the proteoglycan depletion was influenced by the presence of HLA-DR4 in the donor, whether patients with RA or healthy control. The proliferative responses of the RA BMC seemed to correlate inversely with the proteoglycan depletion. We conclude that stimulation of RA BMC with mycobacterial antigens may elicit effector pathways that induce proteoglycan depletion, independent of T cell proliferation.

Adult↗
PubMed1990

The effect of human interleukin 1 on proteoglycan metabolism in human and porcine cartilage explants.

Human interleukin 1 (IL-1), up to 100 pg/ml, causes a decrease of the proteoglycan content of human (old and young) as well as porcine cartilage explants, without stimulating the proteoglycan release from the cartilage. The proteoglycan depletion is stronger in young than in old human cartilage and stronger in human than in porcine cartilage. The proteoglycan synthesis is considerably more inhibited by IL-1 in young than in old human cartilage. Our data suggest that an IL-1 induced inhibition of the proteoglycan synthesis, rather than a stimulation of proteoglycan breakdown causes the proteoglycan depletion of the cartilage. The data furthermore suggest a clear difference between young and old human cartilage, with respect to their sensitivity for IL-1. IL-1 in a concentration of 500 pg/ml causes in all 3 kinds of cartilage explants chondrocyte damage that might be relevant in the cartilage destruction during rheumatoid arthritis.

Aged↗