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T Saxne

Publications and source records attributed to T Saxne.

At least 73 records · Page 4Linked to original sources
PubMed1996

Pristane-induced arthritis in rats: a new model for rheumatoid arthritis with a chronic disease course influenced by both major histocompatibility complex and non-major histocompatibility complex genes.

We present a novel animal model for rheumatoid arthritis induced with a well defined synthetic adjuvant oil, pristane. Two weeks after a single intradermal injection of 150 microliters of pristane, the rats developed severe and chronic arthritis. The inflammation was restricted to the joints and involved pannus formation, major histocompatibility complex (MHC) class II expression, and T lymphocyte infiltration. The initial development as well as the chronic stage of pristane-induced arthritis was ameliorated by treatment with antibodies to the alpha beta-T-cell receptor showing that the disease is T cell dependent. Increased levels of interleukin in serum was seen after pristane injection but not during the chronic stage of arthritis. Joint erosions were accompanied by elevated serum levels of cartilage oligomeric matrix protein. Comparison of MHC congenic LEW strains showed that the severity and chronicity of arthritis varied among the different MHC haplotypes. Rats with RT1f haplotype showed a significantly higher susceptibility to pristane-induced arthritis. A strong influence of non-MHC genes was also suggested by the variability of arthritis susceptibility among different strains with the same MHC haplotype; the most susceptible background was the DA and the least susceptible was the E3. Arthritis induced with a well defined nonimmunogenic adjuvant, with a disease course that closely resembles that of rheumatoid arthritis, makes a suitable animal model for future studies of the pathology and genetics of rheumatoid arthritis.

Animals↗
PubMed1995

Increased release of bone sialoprotein into synovial fluid reflects tissue destruction in rheumatoid arthritis.

OBJECTIVE: Bone sialoprotein (BSP) was quantified in synovial fluids and sera from rheumatoid arthritis (RA) patients to elucidate whether its release from bone relates to the degree of joint tissue destruction. Osteocalcin was assayed for comparison. METHODS: BSP and osteocalcin levels were determined by immunoassays of knee synovial fluids and of sera from RA patients who were selected on the basis of radiographic knee joint tissue damage. RESULTS: Synovial fluid concentrations of BSP increased with increasing degrees of knee joint damage (rs = 0.6848, P < 0.001). Synovial fluid concentrations of osteocalcin did not relate to the degree of joint damage. Serum concentrations of BSP were increased, but did not relate to the degree of joint damage. Serum concentrations of osteocalcin were normal, but increased within the range of normal during progression of joint destruction (rs = 0.4567, P < 0.001). CONCLUSION: Quantification of BSP in synovial fluid holds promise as a useful means of assessing the degree of tissue damage at the molecular level in patients with RA.

Adult↗
PubMed1995

Relationship between serum cartilage oligomeric matrix protein levels and disease progression in osteoarthritis of the knee joint.

The value of serum cartilage oligomeric matrix protein (COMP) as a marker of disease progression was investigated in 81 hospital out-patients with clinical knee osteoarthritis (OA). Progressing patients were defined by a decrease of > or = 2 mm in joint space on X-ray or requiring knee surgery during the 5 yr of follow-up. Of the 57 patients for whom full data were available, 20 progressed and 37 did not progress. Serum COMP levels increased during the first year in those who progressed (mean 6.42 micrograms/ml) (S.D. 6.64) compared to those who did not progress [mean 0.07 microgram/ml (S.D. 4.99); P < 0.001]. Changes in COMP during the first year were related to baseline COMP (r = -0.672, P < 0.001) and weight-to-height ratio (r = 0.272, P = 0.47). After allowing for these variables, serum COMP increased during the first year in progressive patients by 5.04 micrograms/ml [95% confidence interval (CI): (2.61, 7.46)] more than in non-progressive patients. Discriminant analysis gave a sensitivity of 70% and specificity of 78% at a cut-off value of 3.17 micrograms/ml. Baseline serum COMP levels did not differ between the groups but were related to late phase scintigraphy scan abnormalities. These observations suggest that the changes in serum COMP may have prognostic significance and are consistent with a model of OA in which early signs of episodic clinical progression can be found in the cartilage as well as in subchondral bone.

Cartilage↗
PubMed1995

Cartilage and bone metabolism in rheumatoid arthritis. Differences between rapid and slow progression of disease identified by serum markers of cartilage metabolism.

Serum concentrations of specific cartilage and bone molecules reflecting tissue turnover were measured in two well-defined patient groups with early rheumatoid arthritis with distinctly different disease outcome to see if early differences in their levels are prognostic of the rate of joint destruction. Compared with a matched normal population, increased concentrations of cartilage oligomeric matrix protein (COMP) were found in all patients who developed rapid hip joint destruction. In contrast, levels of a putative marker of cartilage aggrecan synthesis, the chondroitin sulfate epitope 846, were increased only in patients with slow joint destruction. Levels of bone sialoprotein (BSP) were increased in both groups, as were levels of the C-propeptide of type II procollagen (CPII), a marker of collagen II synthesis. The increased concentrations of the 846 epitope in patients with slow joint destruction suggest increased aggrecan synthesis. The low levels of the 846 epitope in patients with rapid joint destruction, concomitant with elevated levels of CPII, suggest a selective increase in collagen synthesis. The elevated BSP levels indicate an increased bone turnover in both groups. Thus elevated serum levels of COMP may indicate an unfavorable prognosis for rapid joint destruction, whereas elevated 846 epitope indicates a more favorable prognosis.

Adult↗
PubMed1995

Matrix proteins: potentials as body fluid markers of changes in the metabolism of cartilage and bone in arthritis.

Altered dynamics of cartilage and bone matrix in joint diseases results in increased release of macromolecules into synovial fluid (SF). Such macromolecules are increasingly explored as potential markers of damage and severity. This report focuses on the possibilities of using quantification of tissue specific markers for grading the tissue lesion at the molecular level in arthritis. The theoretical and experimental rationale for such an approach is supported by the results in clinical studies. These studies indicate that simultaneous analysis of multiple cartilage and bone markers in the same SF or serum sample could be useful for defining degree of tissue involvement in rheumatoid arthritis and, possibly, in osteoarthritis.

Arthritis, Rheumatoid↗
PubMed1994

Release of cartilage oligomeric matrix protein (COMP) into joint fluid after knee injury and in osteoarthritis.

OBJECTIVE: The release of fragments of cartilage oligomeric matrix protein (COMP) and aggrecan into knee joint fluid and serum after joint injury and in post-traumatic and primary osteoarthritis was monitored in a cross-sectional study. METHODS: Samples of joint fluid and serum were obtained from healthy volunteers and from patients with arthroscopically verified injury to anterior cruciate ligament and or meniscus of the knee at different times after injury and with different degrees of post-traumatic osteoarthritis. Samples were also obtained from patients with primary osteoarthritis. Fragments of COMP were quantified in joint fluid and in serum by enzyme-linked immunoassay. Fragments of aggrecan were quantified in joint fluid by enzyme-linked immunoassay. RESULTS: Concentrations of COMP and aggrecan fragments in joint fluid in the study groups were increased over the reference levels of 47 (range 10-109) and 34 (range 6-59) micrograms/mL, respectively, in the volunteers with healthy knees. The ratios (w/w) of aggrecan to COMP fragments in joint fluid were also increased in all study groups over that in the reference group. Average concentrations of COMP in joint fluid were high shortly after injury and decreased with time but remained increased over reference levels for many years. Joint fluid COMP concentrations were also increased in early stage post-traumatic and primary osteoarthritis, but not in advanced osteoarthritis. CONCLUSION: Increased amounts of aggrecan and COMP fragments are released into joint fluid after joint injury and in early stage osteoarthritis. The ratios of aggrecan to COMP in joint fluid vary with time after injury and with osteoarthritis disease stage. Although both molecules are sensitive to the agents active in matrix breakdown in joint disease, differences may thus exist in the release mechanisms and attempted repair. The concentrations of the individual markers in body fluids and their ratios may serve to monitor treatment efficacy, disease progression and repair in osteoarthritis and other joint diseases.

Adult↗
PubMed1994

Cartilage metabolism in the injured and uninjured knee of the same patient.

OBJECTIVE: To examine if unilateral knee injury affects the synovial fluid concentrations of aggrecan fragments, cartilage oligomeric matrix protein (COMP) fragments, stromelysin-1, and tissue inhibitor of metalloproteinases-1 (TIMP-1) in the contralateral uninjured knee. METHODS: Synovial fluids from the injured and uninjured knees were obtained at different times in a group of patients after unilateral knee trauma. Serum samples were obtained on the same occasion. Concentrations of aggrecan fragments were determined by precipitation with Alcian Blue; those of COMP fragments, stromelysin-1, and TIMP-1 were measured by immunoassay. Concentrations were compared with those in a reference group of 10 healthy volunteers. RESULTS: Immediately after knee injury, concentrations of aggrecan fragments, COMP fragments, stromelysin-1 and TIMP-1 were increased in the synovial fluid of the injured knee. However, concentrations of aggrecan and COMP fragments, and stromelysin-1 increased also in the contralateral uninjured knee immediately after injury, but less than in the injured knee. Subsequently, the concentrations of all markers decreased in the synovial fluid of the injured knee, but remained unchanged in the uninjured knee. The concentration of aggrecan fragments in the injured knee decreased to less than that in the uninjured knee in the chronic phase. Serum concentrations of COMP were much smaller than those in synovial fluid. CONCLUSIONS: The increased concentrations of aggrecan and COMP fragments and stromelysin-1 in the joint fluid of the contralateral, uninjured knee following unilateral knee injury, compared with concentrations in healthy reference knees, suggest changes in joint cartilage metabolism in both knees following unilateral knee injury. The mechanisms for these changes are unclear. The low serum concentration of COMP makes it less likely that there is any significant 'exchange' of molecular makers between the knees. A further consequence of these findings is that the contralateral knee cannot be recommended as the only control joint in studies of matrix metabolism in patients with unilateral knee injury.

Adult↗
PubMed1994

An extra cysteine in one of the non-calcium-binding epidermal growth factor-like motifs of the FBN1 polypeptide is connected to a novel variant of Marfan syndrome.

We present here a family with a clinical phenotype resembling Marfan syndrome (MFS), and displaying joint contracture and episodes of knee joint effusions, but lacking the cardiovascular features of the syndrome. The phenotype of this family represents a unique mixture of connective tissue symptoms, some of which are found in classical MFS and some of which are typical of dominant ectopia lentis. Linkage analyses suggested a linkage (LOD score 2.4; theta = 0) between the phenotype of the family and a polymorphic marker in the vicinity of the fibrillin locus on chromosome 15 (FBN1). Furthermore, a novel transition mutation was identified in the FBN1 gene in all the affected members of the family. In contrast to the majority of fibrillin mutations reported so far, this mutation substitutes a cysteine for arginine, producing an extra cysteine in one of the non-calcium-binding EGF-like motifs of the fibrillin polypeptide, most probably disturbing the formation of one of the three disulfide bridges known to be essential for the normal conformation of this motif.

Adult↗
PubMed1993

Release of cartilage macromolecules into the synovial fluid in patients with acute and prolonged phases of reactive arthritis.

OBJECTIVE: Extensive changes in articular cartilage metabolism occur during the acute phase of reactive arthritis, as indicated by altered release of cartilage macromolecules into synovial fluid (SF) demonstrated immunochemically. Nevertheless, permanent cartilage lesions are rare in this disease. To monitor specific events during the evolution of reactive arthritis, we investigated the content of cartilage macromolecules in sequentially obtained SF samples from 22 patients. METHODS: Two groups of proteoglycan epitopes, the glycosaminoglycan-rich region of aggrecan (referred to as proteoglycan) and its hyaluronan-binding region (HABr), as well as one matrix protein, cartilage oligomeric matrix protein (COMP), were quantified by immunoassay. RESULTS: SF proteoglycan concentrations, which were initially elevated, decreased significantly with prolonged arthritis, whereas COMP levels changed less markedly and levels of HABr remained stable. There was a positive correlation between SF and serum concentrations of COMP in samples obtained during the early phase of the disease. CONCLUSION: Cartilage involvement in reactive arthritis is transient, in contrast to findings in rheumatoid arthritis. Reactive arthritis should therefore be a suitable model for studies of repair processes in cartilage, which will facilitate understanding of the pathophysiology of cartilage involvement in arthritis.

Adult↗
PubMed1993

Plasminogen activators and plasminogen activator inhibitors in synovial fluid. Difference between inflammatory joint disorders and osteoarthritis.

The plasminogen activator (PA)/plasminogen activator inhibitor (PAI) system is believed to be involved in connective tissue remodelling in joint disease and both PA and PAI production has been shown in several cell types in the joint. We quantified immunoreactive PA and PAI in synovial fluid (SF) and correlated their levels to levels of cartilage derived proteoglycans, radiologically visible joint involvement and to signs of local inflammation. PAI-2 concentrations were increased, compared to normal plasma levels, in patients with rheumatoid arthritis (RA) and reactive arthritis, but not in patients with osteoarthritis (OA). Thirty percent of the patients with RA, but no patient with OA had increased concentrations of PAI-1. Increased concentrations of urokinase type PA (u-PA) were found in RA but not in OA. Tissue type PA (t-PA) concentrations were low in both disease groups. SF proteoglycan concentrations did not correlate with levels of PA or PAI. Concentrations of PAI-2 correlated significantly with SF leukocyte count and cytidine deaminase (CD) activity and u-PA concentrations correlated with CD activity. Both PAI-2 and u-PA were detected in supernatants from lysed polymorphonuclear cells. This suggests that in addition to release from synovial cells and chondrocytes these components may also be released from polymorphonuclear cells. Our results support a pathophysiological role for the fibrinolytic system in joint disease, possibly more pronounced in inflammatory disorders than in OA.

Adult↗
PubMed1992

Synovial fluid analysis of two groups of proteoglycan epitopes distinguishes early and late cartilage lesions.

OBJECTIVE: To investigate whether fragmentation of proteoglycans in arthritis results in domains that have different levels of release from cartilage at different stages of the disease. METHODS: Two regions of the proteoglycan, the hyaluronan-binding region and the glycosaminoglycan-rich region of the core protein, were measured, by immunoassay, in knee joint synovial fluids of patients with rheumatoid arthritis or reactive arthritis. RESULTS: Synovial fluid concentrations of the glycosaminoglycan-rich region were highest in rheumatoid arthritis patients who had little cartilage damage as determined by radiography, whereas release of the hyaluronan-binding region predominated in patients with advanced cartilage destruction. In reactive arthritis, release of the glycosaminoglycan-rich region predominated. CONCLUSION: These findings indicate that the hyaluronan-binding region is initially retained in the tissue during the development of cartilage destruction. The combined analysis of these markers offers a new avenue for assessment of the degree of cartilage damage in arthritis.

Adult↗
PubMed1992

Cytidine deaminase and lactoferrin in inflammatory synovial fluids. Indicators of local polymorphonuclear cell function?

Cytidine deaminase (CD) is a cytoplasmatic enzyme present predominantly in polymorphonuclear cells (PMNC) in inflamed joints. Lactoferrin is situated in the secondary granules of PMNC and is released by secretory/phagocytic stimuli, whereas CD is released mainly upon cell lysis. To study the release of these molecules in arthritic conditions we measured CD and lactoferrin levels in synovial fluid (SF) drawn from patients with rheumatoid arthritis (RA), crystal pyrophosphate disease (CPPD), psoriatic arthropathy, reactive arthritis, spondylarthropathy, and osteoarthrosis. CD activity was highest in SF from RA and CPPD followed by psoriatic arthropathy, reactive arthritis and spondylarthropathy. Lactoferrin concentrations were highest in CPPD followed by RA, reactive arthritis, psoriatic arthropathy, and spondylarthropathy. Both CD and lactoferrin levels were low in osteoarthrosis SF. Although SF CD activity and lactoferrin levels correlated well in all diagnostic groups, the ratio between CD and lactoferrin was higher for RA, psoriatic arthropathy, and spondylarthropathy compared to reactive arthritis and CPPD. This suggests predominant release by PMNC lysis in the more chronic arthritis groups and more degranulation in the more episodic CPPD and reactive arthritis groups. CD activity and lactoferrin levels correlated significantly with SF cell counts in the RA and psoriatic arthropathy groups.

Arthritis, Psoriatic↗
PubMed1992

Cartilage oligomeric matrix protein: a novel marker of cartilage turnover detectable in synovial fluid and blood.

Cartilage oligomeric matrix protein (COMP) is a tissue specific non-collagenous matrix protein. We have developed an enzyme-linked immunosorbent assay for the detection of this protein in synovial fluid and serum. The protein has been quantified in these fluids in patients with rheumatoid arthritis (RA), reactive arthritis, juvenile chronic arthritis, osteoarthritis and in sera of control subjects. The protein was detectable in all fluids and the synovial fluid levels were always higher than in serum in paired samples. The highest knee joint synovial fluid levels were found in reactive arthritis patients and the lowest in RA patients with advanced destruction of the knee joint. However, the relative synovial fluid content of COMP was higher in these RA patients than in patients with advanced osteoarthritis. In patients with long-standing reactive synovitis the concentrations decreased. This decrease, however, was less marked than for proteoglycan concentrations. The serum concentrations were low in patients with juvenile chronic arthritis and in patients with RA with advanced cartilage destruction of the studied knee joint. In the other groups serum levels did not differ between groups or from controls.

Adult↗
PubMed1992

Increased serum concentrations of cartilage oligomeric matrix protein. A prognostic marker in early rheumatoid arthritis.

Two cartilage specific macromolecules, cartilage oligomeric matrix protein (COMP) and proteoglycan, were quantified by immunoassay in sera of two groups of patients with rheumatoid arthritis (RA) of recent onset to evaluate the prognostic value of such measurements. Patients with rapidly progressive joint destruction had increased COMP concentrations initially, which subsequently decreased. A group with more benign disease, and less extensive joint damage, had normal COMP levels throughout the study period. Serum concentrations of proteoglycan were normal in both groups. Thus measurement of COMP in serum early in the course of RA holds promise as a prognostic marker for development of joint destruction in this disease.

Adult↗
PubMed1991

Serum concentrations of hyaluronan and proteoglycan in joint disease. Lack of association.

Circulating hyaluronan originating from the synovial membrane and circulating proteoglycan released from cartilage were determined by specific assays in patients with osteoarthritis (OA), rheumatoid arthritis (RA), reactive arthritis or juvenile chronic arthritis (JCA). Elevated hyaluronan concentrations were found in OA and RA, suggesting proliferation of the synovial membrane in both diseases. The proteoglycan concentrations were highest in OA and polyarticular JCA indicating increased turnover of cartilage matrix. The concentrations of the macromolecules did not correlate except in the group with JCA. Serum concentrations of hyaluronan and proteoglycan thus differ between disease groups and may reflect different aspects of the arthritic process.

Adolescent↗