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ID PMID Title PublicationDate abstract
8310205 Expression of the components and regulatory proteins of the alternative complement pathway 1993 We have studied synthesis of the complement components and regulatory proteins of the alternative pathway and the membrane attack complex in synovial membrane. RNA was extracted from synovial tissue of patients with rheumatoid arthritis (RA) or osteoarthritis (OA) as well as from normal synovial membrane. Dot blot analysis showed the presence of mRNAs for all the complement components and regulatory proteins (C3, factor B, factor D, C5, C6, C7, C9, factor H, factor I, S-protein, SP-40, 40, DAF, MCP, CR1, CD59), except for properdin, C8 alpha, C8 beta and C8 gamma in all three types of synovial membrane studied. In an attempt to determine which components were synthesised by each cell type, monocytes (mononuclear phagocytes), human umbilical vein endothelial cells (HUVEC), synovial membrane fibroblasts (from normal, OA and RA synovial membrane) and peripheral blood lymphocytes were cultured in vitro and secretion rates of individual components were measured and total cellular RNA analysed by northern blotting. Monocytes secreted properdin, C3, and factor H but not factor B, factor I, C5, C6, C7, C8 or C9. Fibroblasts and endothelial cells secreted factor B, factor H and factor I, but not properdin, C5, C6, C7, C8 or C9. Lymphocytes did not secrete any of these components. mRNAs encoding C3, factor B, factor H, S-protein, SP-40, 40, MCP and DAF were detected in all three other cell types (monocytes, fibroblasts and HU-VEC), but factor I and CD59 mRNAs were not detected in monocytes. C5, C6, C7, C8 alpha, C8 beta, CD8 gamma and C9 mRNAs were not detected in any of the cell types studied.(ABSTRACT TRUNCATED AT 250 WORDS)
8185690 A randomized, double-blind, 24-week controlled study of low-dose cyclosporine versus chlor 1994 May OBJECTIVE: To investigate whether low-dose cyclosporin A (CSA) is safe and effective in comparison with chloroquine (CQ) in patients with early rheumatoid arthritis (RA). METHODS: We performed a randomized, double-blind study comparing CSA with CQ in patients with early RA (duration < 2 years) who had had active disease for at least 3 months. Forty-four RA patients with a mean disease duration of 6 months were randomly allocated to receive CSA (initial dosage 2.5 mg/kg/day, maintenance dosage 3.6 mg/kg/day) or CQ (initial dosage 300 mg/day, maintenance dosage 100 mg/day) for 24 weeks. RESULTS: Five patients (2 taking CSA and 3 taking CQ) discontinued the study prematurely. Intention-to-treat analysis disclosed a decrease in the swollen joint count by 7 in both groups. The erythrocyte sedimentation rate and C-reactive protein level did not change significantly. CSA and CQ were tolerated equally well, although mild paraesthesia occurred more frequently in the CSA-treated group. The serum creatinine level increased by 13 mumoles/liter (95% confidence interval [95% CI] 4, 22) in the CSA group and by 6 mumoles/liter (95% CI 1, 11) in the CQ group (difference not statistically significant). CONCLUSION: Both CSA and CQ are effective in alleviating the symptoms of active early RA. There is only slightly impaired renal function after 24 weeks of drug administration of either drug in patients with early RA.
8564571 [Treatment of inflammation with anti-inflammatory cytokines: example in models of auto-imm 1995 Cytokines may exert anti-inflammatory properties, allowing the hypothesis of their potential therapeutic use. Targeting the cytokines balance may modify the course of subsequent inflammatory events in an autoimmune disease. Many data are available. Interferon-gamma can be blocked by an anti-interferon-gamma monoclonal antibody: if the treatment is administered in the early phase of an autoimmune disease such as collagen-induced arthritis, the course of the disease is worsened; if the treatment is given later, the disease can be improved; these results are mirrored by treatment with high doses of the cytokine itself. Pharmacologic effects of antiinflammatory cytokines such as interleukin (IL)-4, IL-10 or IL-13 are a protection against several experimental autoimmune diseases. The very short half-life of cytokines makes them difficult and expensive to use directly; in such occurrence, high quantities have to be frequently injected. In this context, gene therapy appears as an effective alternative solution: the transfection of cells with cytokines genes (e.g. either IL-4 or IL-13) then the engraftment of these vectors in animals, permit the in vivo secretion of high levels of cytokines, and result in the protection of the animals from the development of the disease.
7807973 A new double labeling technique for combined in situ hybridization and immunohistochemical 1994 Dec BACKGROUND: A reliable, sensitive, and specific double labeling technique is required that allows the simultaneous visualization of in situ hybridization products and antigens. Currently used double labeling techniques are limited by various problems including the numerous disadvantages associated with radioactive labels, the time-dependent loss of fluorescence signals, and the high background that is associated with various peroxidase techniques. Therefore, the aim of this study was to develop an improved double labeling technique. EXPERIMENTAL DESIGN: Riboprobes were used for detection of mRNA of cathepsin D, vascular cell adhesion molecule, and endothelial leukocyte adhesion molecule in in situ hybridization and monoclonal antibodies specific for macrophages and basement membranes (collagen type IV) for immunohistochemical analysis. The in situ hybridization and immunohistochemical analysis were used to characterize cathepsin D messenger ribonucleic acid (mRNA) in macrophages expressing cells and the expression of adhesion molecule mRNA in endothelial cells delineated by the vascular basement membrane expressing collagen type IV. RESULTS: The application of in situ hybridization detection systems before immunohistochemical analysis was shown to give reliable results. In situ hybridization with digoxigenin labeled riboprobes using alkaline phosphatase linked Fab fragments visualized by 4-nitro blue tetrazolim chloride/5-bromo-4-chloro-3-indolphosphate combined with immunohistochemical detection of the antigen by the alkaline phosphatase anti-alkaline phosphatase-technique with new fuchsin as substrate is a reliable double labeling technique. Using this protocol, we could show that the reaction product is stable, there is virtually no background, and both reaction products can be easily distinguished. Vascular cell adhesion molecule-1 mRNA is expressed only in endothelial cells and certain fibroblast-like cells that do not label with antibodies against macrophages, whereas cathepsin D mRNA is coexpressed with macrophages. We also demonstrated that endothelial leukocyte adhesion molecule-1 mRNA is strongly expressed in endothelial cells that can be localized within the boundaries of the vascular basement membrane. CONCLUSIONS: A new and reliable double labeling technique for the simultaneous evaluation of in situ hybridization and immunohistochemical analysis is described that is suitable for various applications.
8742620 Production of the third component of complement (C3) by peripheral polymorphonuclear neutr 1995 Oct Normal human polymorphonuclear neutrophils (PMN) can spontaneously produce the third component of complement (C3) in in vitro culture as detected by ELISA. This C3-producing capacity of PMN can be augmented by TNF-alpha (20 ng/ml) and bacterial lipopolysaccharide (100 ng/ml), but not by IL-1 beta or IL-8. The C3 production by PMN was found to be temperature dependent and was suppressed by the addition of protein inhibitor. The C3 mRNA in PMN could be detected by reverse transcription assisted polymerase chain reaction (RT-PCR) after TNF-alpha or LPS stimulation for 6 hours. To further understand C3 production by peripheral blood PMN in rheumatoid arthritis (RA), spontaneous and TNF-alpha stimulated production of C3 by peripheral PMN were compared in 15 cases of active RA, 15 inactive RA and 15 normal individuals. We failed to find any significant difference among the three groups. We conclude that PMN plays a negligible role in C3 hypercomplementemia in patients with active RA.
8441142 Abnormalities in bone marrow mononuclear cells in patients with rheumatoid arthritis. 1993 Jan We analyzed the cell surface phenotype and the function of mononuclear cells in peripheral blood and in bone marrow of patients with rheumatoid arthritis (RA). The monoclonal antibodies anti-CD45RA, anti-CD29 and anti-S6F1 identify the suppressor-inducer (CD4+CD45RA+), helper-inducer (CD4+CD29+) and killer-effector (CD8+S6F1+) subpopulations of lymphocytes, respectively. In patients with RA, peripheral blood samples showed the same percentage of CD4+CD45RA+, CD4+CD29+ and CD8+S6F1+ cells as seen in control subjects. In contrast, in the bone marrow of patients with RA we observed a significant decrease in CD4+CD45RA+ cells, a significant increase in CD8+S6F1+ cells compared with findings in peripheral blood and in bone marrow samples from control subjects. Consistent with the phenotypic changes observed, bone marrow T cells also showed functional abnormalities, since autologous mixed lymphocyte reaction-activated CD4 cells from bone marrow of patients with RA showed a decrease in suppressor-inducer activity and CD8+ cells activated by allogenic E- cell showed an increase in killer-inducer activity. The changes noted above may contribute to the immunologic abnormalities that occur in this disease and provide insight into the pathophysiology of RA.
1592120 IL-1 beta, a strong mediator for glucose uptake by rheumatoid and non-rheumatoid cultured 1992 May 25 Higher basal 2-deoxy-D-glucose uptake in rheumatoid synovial cells than in non-rheumatoid synovial cells, was found to be associated with an increased interleukin-1 beta (IL-1 beta) secretion (respectively 850 +/- 238 vs. 8.3 +/- 2.4 pg/24 h/10(5) cells, mean +/- S.E.M.). When exogenous human recombinant IL-1 beta was added to cultures, a marked stimulation of 2-deoxy-D-glucose uptake was performed by both human synovial cultured cells, in a time-dependent and dose-dependent manner (IL-1 beta 0-100 ng/ml). In non-rheumatoid synoviocytes, stimulation occurred 1-3 h following the addition of 1 ng/ml interleukin-1 beta and increased up to 24 hours (respectively +150% and +261.4% after 6 and 24 hours association time). Rheumatoid synovial cells were less sensitive to 1 ng/ml IL-1 beta (respectively +80% and +146.4%). IL-1 beta increased significantly the Vmax for 2-deoxy-D-glucose uptake by synovial cells, with no change in the Km. This effect was protein synthesis-dependent, and not secondary to prostaglandin E2 synthesis or cell growth. IL-1 beta possesses an important effect on glucose homeostasis in synovial cells, which could be indirect and/or regulated by the presence of natural inhibitors.
7554553 The role of interleukin-8 and other cytokines in the pathogenesis of Felty's syndrome. 1995 May OBJECTIVE: Felty's syndrome (FS) is defined as rheumatoid arthritis (RA) with neutropenia and, in some cases, splenomegaly; the outcome is primarily determined by the risk of infection, which is related to the degree of neutropenia. We analysed whether the clinical manifestations of FS, especially neutropenia, could be explained by abnormalities in cytokine production. METHODS: We examined the production in FS of five cytokines involved in the maturation and activation of polymorphonuclear cells (PMNs): IL-1 beta, TNF alpha, IL-8, G-CSF and GM-CSF. Because of the role of systemic IL-8 in neutrophil migration, serum IL-8 levels were also evaluated. RESULTS: Spontaneous and anti-CD16 stimulated cytokine production was similar in FS, RA and healthy controls (NC). However, anti-CD3 stimulated IL-8 production was significantly increased compared to NC in both RA and FS. FS patients who spontaneously produced G-CSF in culture were protected from bacterial infections. Serum IL-8 levels were elevated in FS and RA compared to NC (p < 0.001 for both groups). In FS, serum IL-8 was higher in patients with a history of bacterial infections compared to those without (p < 0.01) and there was a weak inverse correlation between neutropenia and serum IL-8 levels (Kendal's tau B = -0.31, p = 0.05). CONCLUSION: The neutropenia of FS cannot be explained by changes in peripheral blood cytokine production, although changes in the bone marrow microenvironment cannot be excluded. Our data do suggest a possible role for G-CSF and IL-8 in the development of certain FS complications.
8557699 Monocyte chemotactic factor in rheumatoid arthritis synovial tissue. Probably a cross-link 1996 Jan 12 The extracts of rheumatoid arthritis-synovial lesions from seven patients possessed a strong chemotactic activity for monocytes and a negligible one for polymorphonuclear leukocytes. These results are consistent with a prominent histological feature of the synovial lesion, the mononuclear cell predominant infiltration. The major monocyte chemotactic factor in the synovial tissue extracts was purified to a single protein peak in reverse phase high performance liquid chromatography with a C4 column. NH2-terminal amino acid analysis of the initial 20 residues yielded a single sequence. Surprisingly, this sequence was completely identical to that of S19 ribosomal protein. The purified sample demonstrated two protein bands in SDS-polyacrylamide gel electrophoresis with apparent molecular masses of 34 and 68 kDa. These sizes were 2 and 4 times that of S19 ribosomal protein, suggesting that the chemotactic factor would be a dimer or tetramer of S19 ribosomal protein cross-linked by factor XIIIa. A recombinant human S19 ribosomal protein was prepared as a fusion protein with a maltose binding protein in Escherichia coli. After treatment with factor XIIIa, cross-linked recombinant S19 ribosomal protein exhibited the monocyte chemotactic activity, although the untreated recombinant protein did not.
7729275 Misoprostol coadministered with diclofenac for prevention of gastroduodenal ulcers. A one- 1995 May The objective of this study was to determine the long-term efficacy of misoprostol in preventing diclofenac-induced gastroduodenal ulcers in rheumatoid arthritis and osteoarthritis patients. Three hundred eighty-four patients who had an endoscopically confirmed gastric or duodenal lesion that had healed with misoprostol therapy were randomized to receive misoprostol or placebo coadministered with diclofenac for up to 52 weeks. Endoscopic examinations were repeated at weeks 12, 24, and 52. The development of a gastric and/or duodenal ulcer was considered a prophylaxis failure. Results in the evaluable cohort of patients demonstrated that gastroduodenal ulcer incidences were lower with misoprostol than placebo for all study periods (0-12 weeks, 7% vs 23%; 0-24 weeks, 11% vs 26%; and 0-52 weeks, 15% vs 31%). Misoprostol did not interfere with the antiarthritic effects of diclofenac. In conclusion, misoprostol coadministered with diclofenac for 12 months to patients with rheumatoid arthritis or osteoarthritis significantly reduced the incidence of diclofenac-induced gastroduodenal ulcers (P < or = 0.018).
7697682 Effect of interferon therapy in a patient with chronic active hepatitis type C associated 1994 Nov Interferon (IFN) is widely used to treat patients with chronic hepatitis types B and C but has been found to occasionally aggravate rheumatoid arthritis (RA) or cause interstitial pneumonia. We administered 6 MIU/d IFN-beta by intravenous injection for 6 weeks to a 55-year-old man with chronic active hepatitis type C associated with RA and interstitial pneumonia. Transaminase levels rapidly returned to normal after treatment and hepatitis C virus-RNA (nested RT-PCR method) was negative on completion of treatment. No significant adverse reactions or aggravation of RA or interstitial pneumonia occurred. These findings suggest that use of IFN-beta in the treatment of patients with chronic hepatitis type C associated with RA and/or interstitial pneumonia presents no problem if appropriate precautions are taken.
1400895 Superantigens: biology, immunology, and potential role in disease. 1992 May Superantigens are unique products of bacteria and viruses which, in combination with class II major histocompatibility complex molecules, are capable of stimulating a large fraction of T cells in an affected individual. This stimulation primarily involves the variable region of the T cell receptor beta chain (V beta). The discovery of superantigens and the elucidation of their immunologic properties have provided valuable tools for the investigation of the immune system in both normal and diseased animals. Most importantly, recent work suggests that superantigens play a role in a number of diverse pathological conditions, including toxic shock syndrome and autoimmune diseases such as rheumatoid arthritis.
8235290 Levels of soluble receptors for tumor necrosis factor type I and type II in paired synovia 1993 The objective of this study was to determine whether levels of soluble receptors for tumor necrosis factor type I and type II (sTNF-RI and sTNF-RII) as measured in paired synovial fluids (SF) of arthritis patients are associated with clinical or laboratory parameters of local inflammation. sTNF-RI and -RII were measured by ELISA. We found that sTNF-RI and -RII did not correlate with activity of local inflammation. sTNF-RI levels correlated with sTNF-RII concentrations. We concluded that sTNF-RI and -II did not represent markers for local disease activity in arthritis patients.
7809146 Control of autoantibody affinity by selection against amino acid replacements in the compl 10 heavy chain variable region segment from both n Rheumatoid factor (RF) autoantibodies can be produced in healthy individuals after infections or immunizations and thus escape normal tolerization mechanisms. It has not been clear whether such autoantibodies can undergo somatic hypermutation and affinity maturation similar to antibodies to exogenous antigens. We have investigated how these autoantibodies are regulated in normal individuals by analyzing the sequences of monoclonal IgM RFs obtained as hybridomas from donors after immunization. The variable regions undergo extensive hypermutation, but in contrast to antibodies against exogenous antigens, there is a strong selection against mutations that result in replacement of amino acids in the hypervariable, or complementarity-determining, regions. Furthermore, we found no increase in affinity of these RFs with the accumulation of mutations. This suggests that high-affinity variants are tolerized during the hypermutation process and there is a peripheral mechanism operating on certain autoreactive B cells that, while not deleting or anergizing all autoreactive cells, prevents the generation of high-affinity autoantibodies. Comparison of RFs by using the VH1 DP-10 heavy chain variable region segment from both normal individuals and rheumatoid arthritis (RA) patients suggests that RF from RA patients may not be subject to such a controlling mechanism.
8153315 MR imaging of the arthritic knee: improved discrimination of cartilage, synovium, and effu 1994 May PURPOSE: To assess the applicability of three-dimensional (3D) magnetic resonance (MR) imaging with pulsed saturation transfer (ST) or fat saturation in depicting articular structures in arthritic knees. MATERIALS AND METHODS: Eleven patients underwent MR imaging with T1-weighted spin-echo (SE); unenhanced and contrast material-enhanced T2*-weighted 3D gradient-echo with and without on-resonance pulsed ST; and T1-weighted, fat-presaturated 3D gradient-echo techniques. Images with ST were subtracted from those without ST. RESULTS: Both fat-suppressed imaging and ST-subtraction (STS) techniques generated a high contrast-to-noise ratio among cartilage, synovium, effusion, bone, and adipose tissue. Both techniques depicted hypertrophic synovial tissue on unenhanced images; contrast material was necessary to differentiate between synovium and cartilage on STS images. CONCLUSION: 3D MR imaging with fat-suppressed or STS techniques provides good discrimination among articular structures in arthritic knees. Fat-suppressed imaging is faster than STS imaging and offers better contrast between cartilage and synovium. These techniques may improve monitoring of arthritic disease progression and therapeutic response.
1563146 The effects of implant design on range of motion after total knee arthroplasty. Total cond 1992 May Range of motion (ROM) after total knee arthroplasty (TKA) is an important variable in determining clinical outcome. Recent design modifications have been aimed at improving final motion. The posterior stabilized total knee prosthesis was introduced as a modification of the total condylar design, changing the center of curvature of the femoral component to allow greater ROM. In this study, all primary TKAs performed at the authors' institution from July 1982 until December 1986 were reviewed to determine the effect of this design modification on outcome. A total condylar (TC) group comprised 51 arthroplasties and was compared to 53 arthroplasties in a posterior stabilized (PSTC) group. the postoperative protocol was identical in both groups. The mean postoperative flexion was 11 better in the PSTC group; however, the mean preoperative flexion had initially been 10 degrees better in the PSTC group. The maximum flexion achieved by any patient in both groups was similar, but the TC group actually gained slightly more arc of motion. The better motion in the PSTC group may be secondary to better motion preoperatively and not implant design in this series. The more limited the preoperative ROM, the greater the quadriceps stiffness is likely to be, which is an important determinant of postoperative flexion. Review of the literature supports present observations that a group with less mean preoperative motion paradoxically gains a slightly greater increment of flexion. Differences in flexion after TKA are difficult to attribute to design in either the current study or by a review of the literature. This is because determinants of flexion after TKA are multifactorial and outcome data limited, notwithstanding the similarities among modern prostheses.
7612044 High level of interleukin-10 production by the activated T cell population within the rheu 1995 Jul OBJECTIVE: To characterize the cytokine profile of the activated T cell population derived from the synovial membrane of rheumatoid arthritis (RA) patients. METHODS: Interleukin-2 (IL-2) was used to select for in vivo-activated T cells from the synovial membrane of 2 patients with RA, and the cells were cloned nonspecifically. The cytokine production profile of these clones was compared with that of clones derived from peripheral blood monocytes (PBM) by stimulating all clones for 24 hours with immobilized anti-CD3 (coated at 10 micrograms/ml) or phorbol-12-myristate-13-acetate (10 ng/ml) plus soluble anti-CD3 (1 microgram/ml). Interferon-gamma (IFN gamma), IL-4, and IL-10, the cytokines that discriminate between Th1 and Th2 cells and are involved in immunoregulation, were assayed by enzyme-linked immunosorbent assay. RESULTS: There was a difference in the cytokines produced by the clones derived from the rheumatoid membranes compared with clones derived from the periphery. Clones derived from both membranes and PBM were mostly IFN gamma-producers, i.e., either a Th0 or a Th1 profile. There was a high proportion of IFN gamma/high IL-10-producing cells derived from the joint, but not from the periphery. Of clones derived from the synovial membrane of each of 2 RA patients, 100% and 50% produced both 1-10 ng/ml IFN gamma and > 7 ng/ml IL-10, compared with < 7% of clones derived from normal or RA peripheral blood. In addition, when autologous membrane and PBM were compared, the mean concentration of IL-10 produced by the clones derived from the synovial membrane sample was significantly different from those produced by clones derived from peripheral blood (P < 0.02). CONCLUSION: The cytokine profile of the T cell clones that were obtained from the RA joint after expansion with IL-2 is distinct from that of the T cells that are predominant in PBM. This supports the concept that the T cells subsets that accumulate in the joint are not a random sample. The high level of IL-10 production by clones derived from the synovium suggests that this cytokine may be a major contributor to the endogenous immunosuppression that occurs in RA.
7564266 Expression of basic fibroblast growth factor in synovial tissue from patients with rheumat 1995 Sep BACKGROUND: Recent studies have implicated polypeptide growth factors in the development of rheumatoid arthritis (RA), which is characterized by synoviocyte hyperplasia and neovascularization. One such polypeptide, basic fibroblast growth factor (bFGF), is of particular interest because of its potent mitogenic and angiogenic activities. We have previously reported that cultured human synoviocytes synthesize and bind bFGF and also proliferate in response to it (1). Recently, we found a close association between increased bFGF expression and destructive changes in arthritic joints from rats (2). Now we extend our study by detecting in vivo expression of bFGF in human synovial tissues obtained from patients with RA. EXPERIMENTAL DESIGN: Human synovial tissues from patients with RA, degenerative joint disease (DJD), and trauma were collected during joint surgery. The expression of bFGF protein and mRNA by the synovia was examined by immunolocalization, Western blot, Northern blot, and RNase protection assays. Synovium from patients with DJD and trauma was used to compare with rheumatoid synovium. Double immunostaining with cell type-specific antibodies was carried out to identify cellular sources of bFGF. RESULTS: Both polypeptide and mRNA for bFGF were detected in the synovial samples examined. Increased bFGF staining was found in synovium-cartilage interface where joint destruction occurred and in hyperplastic synoviocytes of a subset of rheumatoid synovium. Strong cytoplasmic bFGF staining was localized in the majority of mast cells and vascular cells. CONCLUSIONS: Synovial tissue from patients with RA, DJD, and trauma express bFGF. Increased bFGF staining in the hyperplastic lining synoviocytes and at the pannus-cartilage interface suggests that bFGF may play a role in synovial hyperplasia and joint destruction. Strong cytoplasmic bFGF staining found in mast cells and vascular cells indicates that these cells are the major sources of tissue bFGF.
8386851 Modulation of receptor bound urokinase-type plasminogen activator on human monocytes by no 1993 It has been shown previously that cell surface bound fibrinolytic activity on human monocytes is significantly increased in patients with rheumatoid arthritis (RA) as compared to monocytes from healthy volunteers. Studies on the modulation of receptor-bound urokinase type plasminogen activator on peripheral blood monocytes of patients with RA showed that tenoxicam, a non-steroidal antiinflammatory drug with long half life and good tissue permeability, is able to downregulate the total number of urokinase receptors. Furthermore the degree of endogenous occupation of the urokinase receptor was significantly decreased in post-treatment monocytes. These data provide evidence that the non-steroidal antiinflammatory drug tenoxicam is able to downregulate cell bound fibrinolytic activity, known to contribute to pronounced degradation of cartilage and connective tissue in patients with RA.
8660108 Concentrations of pyridinoline and deoxypyridinoline in joint tissues from patients with o 1996 May OBJECTIVE: To assess the usefulness of pyridinoline (Pyr) and deoxypyridinoline (Dpyr), intermolecular crosslinks of collagen, as markers in the evaluation of arthritis, by studying their distribution in tissues from knee joints. METHODS: Joint tissues (cartilage, bone, synovium) were obtained during operation from 10 patients with osteoarthritis (OA) and 10 patients with rheumatoid arthritis (RA). Synovium was also obtained from 10 non-arthritic (NA) subjects. Hydroxyproline was measured in hydrolysed tissue samples and converted to an equivalent collagen content. The amounts of Pyr and Dpyr crosslinks measured in the hydrolysed samples using a fluorescence technique were expressed as mumol/mol of collagen. RESULTS: Pyr and Dpyr were distributed in all three tissues, but in different amounts. The ratio of the contents of Pyr and (Pyr:Dpyr) was 50:1 in cartilage, 3:1 in bone, and 25:1 in synovium. OA cartilage had a greater Dpyr content than the RA cartilage, but there was no other significant difference in the contents of Pyr and Dpyr and the ratio Pyr:Dpyr in the joint tissues from patients with OA or RA. In synovium, there was no significant difference between the contents of Pyr and Dpyr and the Pyr:Dpyr ratio among OA, RA, and NA tissues. CONCLUSION: Both Pyr and Dpyr were located in cartilage, bone, and synovium. A significant amount of Pyr and Dpyr in these joint tissues, especially in synovium, may contribute to the urinary excretion of those crosslinks that is observed in arthritis.