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2.  Early prediction of rheumatoid arthritis by serological variables and magnetic resonance imaging of the wrists and finger joints: results from prospective clinical examination 
Annals of the Rheumatic Diseases  2006;65(1):134-135.
doi:10.1136/ard.2005.043075
PMCID: PMC1797983  PMID: 16344501
early stage rheumatoid arthritis; anti‐cyclic citrullinated peptide antibody; magnetic resonance imaging; bone marrow oedema; bone erosion
3.  Procollagen IIC-peptide as a marker for assessing mechanical risk factors of knee osteoarthritis: effect of obesity and varus alignment 
Annals of the Rheumatic Diseases  2000;59(12):982-984.
OBJECTIVE—To ascertain by cross sectional examination whether the concentration of procollagen IIC-peptide in joint fluid significantly correlates with mechanical risk factors of knee osteoarthritis (OA), such as obesity (body mass index) and varus alignment (lateral femorotibial angle).
METHODS—The concentrations of procollagen IIC-propeptide in synovial fluid were measured by a sandwich enzyme immunoassay of 65 patients with the same radiological stage of primary knee OA—that is, Ahlbäk stage I. The relations between procollagen IIC-peptide and body mass index and lateral femorotibial angle were examined using simple regression analysis and multiple regression analysis.
RESULTS—Significant positive correlations were found between procollagen IIC-propeptide concentrations and body mass index (r=0.479, p<0.0001), and between procollagen IIC-propeptide concentrations and lateral femorotibial angle (r=0.375, p=0.0021). Significant correlations were also found by multiple regression analysis. The multiple correlation coefficient of body mass index and femorotibial lateral angle to the procollagen IIC-propeptide concentrations was 0.547 (p<0.0001).
CONCLUSIONS—The findings suggest that synthesis of type II collagen by chondrocytes is enhanced by abnormal mechanical stress, in this case obesity and varus alignment. It is concluded that procollagen IIC-propeptide concentrations in joint fluid are a useful marker of early OA.


doi:10.1136/ard.59.12.982
PMCID: PMC1753041  PMID: 11087702
4.  Matrix metalloproteinases and tissue inhibitors of metalloproteinases in synovial fluids from patients with rheumatoid arthritis or osteoarthritis 
Annals of the Rheumatic Diseases  2000;59(6):455-461.
OBJECTIVE—Matrix metalloproteinases (MMPs) are expressed in joint tissues of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). The objective of this study was to define the steady state levels of seven different MMPs and two tissue inhibitors of metalloproteinases (TIMPs) as well as the potential metalloproteinase activity in the synovial fluid (SF) to provide more insight into the role of MMPs in cartilage destruction in RA and OA.
METHODS—Levels of MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-13, TIMP-1, and TIMP-2 in SF aspirated from knee joints of 97 patients with RA and 103 patients with OA were measured by the corresponding one step sandwich enzyme immunoassays. Proteolytic activity of MMPs in these SFs was examined in an assay using [3H]carboxymethylated transferrin substrate in the presence of inhibitors of serine and cysteine proteinases after activation with p-aminophenylmercuric acetate (APMA). Destruction of RA knee joints was radiographically evaluated.
RESULTS—Levels of MMP-1, MMP-2, MMP-3, MMP-8, and MMP-9 were significantly higher in RA SF than in OA SF. MMP-7 and MMP-13 were detectable in more than 45% of RA SFs and in less than 20% of OA SFs, respectively. Among the MMPs examined, MMP-3 levels were extremely high compared with those of other MMPs. Direct correlations were seen between the levels of MMP-1 and MMP-3 and between those of MMP-8 and MMP-9 in RA SF. Although the levels of MMP-1 and MMP-3 increased even in the early stage of RA, those of MMP-8 and MMP-9 were low in the early stage and increased with the progression of RA. Molar ratios of the total amounts of the MMPs to those of the TIMPs were 5.2-fold higher in patients with RA than in OA, which was significant. APMA-activated metalloproteinase activity in SF showed a similar result, and a direct correlation was seen between the molar ratios and the activity in RA SF.
CONCLUSIONS—Our results show that high levels of MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, and TIMP-1 are present in RA SF and suggest that once these MMPs are fully activated, they have an imbalance against TIMPs, which may contribute to the cartilage destruction in RA.


doi:10.1136/ard.59.6.455
PMCID: PMC1753174  PMID: 10834863
5.  The mutations induced by oxidatively damaged nucleotides, 5-formyl-dUTP and 5-hydroxy-dCTP,in Escherichia coli. 
Nucleic Acids Research  1998;26(20):4582-4587.
The mutational properties of 5-formyl-2'-deoxyuridine 5'-triphosphate (5-CHO-dUTP) and 5-hydroxy-2'-deoxycytidine 5'-triphosphate (5-OH-dCTP), the major oxidatively damaged pyrimidine nucleotides derived from dTTP and dCTP, respectively, were analyzed by an in vivo assay. 5-CHO-dUTP and 5-OH-dCTP were directly incorporated into Escherichia coli , and their mutagenicities were evaluated by the chromosomal lacI forward mutation assay. The mutation frequencies increased, depending on the dose of these damaged nucleotides, indicating that these nucleotides were incorporated into E.coli and acted as mutagens in vivo . The mutagenicities of 5-CHO-dUTP and 5-OH-dCTP were comparable to that of 8-hydroxy-2'-deoxyguanosine 5'-triphosphate, a major form of dGTP oxidative damage. 5-CHO-dUTP induced G.C to A.T, A.T to G.C and G.C to T.A mutations, and 5-OH-dCTP elicited G.C to A.T, A.T to C.G and G.C to T.A mutations.
PMCID: PMC147905  PMID: 9753724
6.  Localization of the binding site of tissue-type plasminogen activator to fibrin. 
Journal of Clinical Investigation  1986;78(1):163-169.
Functionally active A and B chains were separated from a two-chain form of recombinant tissue-type plasminogen activator after mild reduction and alkylation. The A chain was found to be responsible for the binding to lysine-Sepharose or fibrin and the B chain contained the catalytic activity of tissue-type plasminogen activator. An extensive reduction of two-chain tissue-type plasminogen activator, however, destroyed both the binding and catalytic activities. A thermolytic fragment, Fr. 1, of tissue-type plasminogen activator that contained a growth factor and two kringle segments retained its lysine binding activity. Additional thermolytic cleavages in the kringle-2 segment of Fr. 1 caused a total loss of the binding activity. These results indicated that the binding site of tissue-type plasminogen activator to fibrin was located in the kringle-2 segment.
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PMCID: PMC329545  PMID: 3088041
7.  Arthrographic study of the rheumatoid knee. Part 2. Articular cartilage and menisci. 
Annals of the Rheumatic Diseases  1981;40(4):344-349.
The changes of the articular cartilage and of the menisci in 129 knee joints with classical rheumatoid arthritis have been investigated by an improved arthrographic technique. The changes of the intra-articular components on the arthrograms coincided well with direct views at arthroscopy and surgery. The changes of the articular cartilage on the arthrograms were graded as normal, deposit and pooling, thinning, filling defect, destruction, and disappearance, and those of the menisci as normal, degeneration, tear, and disappearance. The results showed that: (1) The radiographs did not always reflect the changes of those intra-articular components in the early stages; especially in stage 2 they showed various conditions from intact to destruction. (2) The changes of the menisci were less advanced than those of the articular cartilage in the early stages. (3) The changes in those components progressed almost symmetrically in both compartments. It is necessary to appreciate not only the pathological condition of the bones of the knee joints but also that of the intra-articular components to devise more careful programmes of treatment for rheumatoid knees.
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PMCID: PMC1000726  PMID: 6894843
8.  Arthrographic study of the rheumatoid knee. Part 1. Synovial proliferation. 
Annals of the Rheumatic Diseases  1981;40(4):332-343.
The improved method of double-contrast arthrography for the knee joint, which can give extensive information on the intra-articular components, was undertaken in 131 knee joints with classical rheumatoid arthritis. Synovial proliferation was classified by its localisation into 6 types: nonproliferated (NP); localised, subdivided into suprapatellar pouch (SPP), proper articular (PA), and posterior (POST); panarticular (PAN); and burned out type (BO). These types are intimately related to the radiological stage and pathological changes of the articular cartilage and menisci. By following the dynamic changes of synovial proliferation by arthrography the clinical course of the rheumatoid knee joint may be predicted. While in the NP and SPP types destruction of the joint is minimal, it is relatively rapid and severe in the PA and PAN types. Thus the proliferation in the joint proper has a stronger influence on joint destruction than does the suprapatellar pouch. From these results synovectomy to resect proliferated synovial tissues of the joint proper completely, and to resect those of the suprapatellar pouch only superficially in the early stage, was undertaken in 21 rheumatoid arthritic joints, giving excellent results in 80.9%. The advantages of this method are discussed.
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PMCID: PMC1000725  PMID: 6894842

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