Objective-The first complement component C1s was reported to have novel functions to degrade matrix components, besides its activities in the classic complement pathway. This study explores participation of C1s in articular cartilage degradation in rheumatoid arthritis (RA). Methods-Normal articular cartilage (n=6) and cartilage obtained from joints with RA (n=15) and osteoarthritis (OA, n=10) were immunostained using antiC1s monoclonal antibodies PG11, which recognises both active and inactive C1s, and M241, which is specifically reactive to activated C1s. The eVects of inflammatory cytokines on C1s production by human articular chondrocytes were also examined by sandwich ELISA. Results-In normal articular cartilage, C1s was negative in staining with both PG11 and M241. In contrast, degenerating cartilage of RA was stained with PG11 (14 of 15 cases), and in most of the cases (13 of 15 cases) C1s was activated as revealed by M241 staining. In OA, C1s staining was restricted in severely degrading part of cartilage (5 of 10 cases), and even in that part C1s was not activated. In addition, C1s production by chondrocytes in vitro was increased by an inflammatory cytokine, tumour necrosis factor . Conclusion-These results suggest that C1s activated in degenerative cartilage matrix of RA but not in that of OA. C1s is thought to participate in the pathogenesis of RA through its collagenolytic activity in addition to the role in the classic cascade.

The secondary ossification center of 14- to 16-day-old hamster tibiae was examined immunohistochemically with active and inactive Cls-specific antibodies, RK5 and RK4, respectively. At the ossification center, chondrocytes differentiate from proliferating and hypertrophic to degenerating stages, and their site is occupied by the bone marrow. Cls was strongly immunostained in hypertrophic chondrocytes. In order to discover whether Cls is activated at a particular site, the cartilage was immunostained with RK5 and RK4. RK5 mainly reacted with degrading matrix around invading vessels. In contrast, RK4 strongly stained hypertrophic chondrocytes. Immunoelectron microscopy revealed Cls on degrading fragments of chondrocytes and fibers of cartilage matrix. Decorin, one of the major matrix proteoglycans, was dose and time dependently degraded by Cls. Type II collagen and type I gelatin were also degraded. Articular cartilage from patients with rheumatoid arthritis was positively immunostained (11/12 cases) with an anti-Cls monoclonal antibody (mAb) PG11, whereas normal articular cartilage (5/5 cases) was negative, suggesting Cls participation in the etiology of rheumatoid arthritis.

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Abstract:Ground reaction forces, temporal factors, and distance factors of hemiplegic gait were measured by the force plates. Subjects were 145 patients with hemiplegia, 106 males and 39 females, whose ages were from 25 to 84 years. The measurements were done more than 6 months after the onset of cerebrovascular diseases. The principal component analysis was executed on quantitative parameters calculated from three components of ground reaction forces. The quantitative parameters were the symmetry, the reappearance, the smoothness, and the sway indices introduced by Yamazaki and the deceleration, the acceleration, and the weight bearing indices introduced by Miyazaki. The relations between principal component scores and clinical estimations of hemiplegic gait, which were the mobility level, the visual assessment of the truncal sway, the visual assessment of the ability of weight bearing on affected legs, and the step sequence during gait, were investigated. Three major principal components were found significant. The first principal component score correlated significantly to all clinical estimations (is, from 0.44 to 0.63) and the gait speed (r=0.88).Significant correlations were also found between the score of the second principal component and the symmetric ratio, which meant stance phase of affected leg/stance phase of sound leg (r=0.47), and the score of the third principal component and the decelerate index (r=0.88).It was found that the first, the second, and the third principal components indicated the level of general walking ability, the gait symmetry, and the deceleration factor during gait, respectively. It will be possible to evaluate the hemiplegic gait of stroke patients quantitatively using 3 principal component scores shown here. (Jpn J Rehabil Med 1998; 35: 477-484)

Background Biologics improved Rheumatoid Arthritis (RA) treatment dramatically and we have abundant evidence on its high efficacy, especially on preventing joint destruction. However, we do not have enough evidence on its efficacy in halting progression of weight bearing joint destruction. There is a study reporting that biologics can stop joint destruction under Larsen Grade (LG) II, while joint destruction continues for LG III and IV. 1 Objectives In our experiences, we have many cases that required total knee arthroplasty (TKA) even when baseline LG was II or lower. X-ray may not be sensitive enough to detect inflammation, but Magnetic Resonance Imaging (MRI) can detect inflammation more accurately and precisely. MRI evaluation is expected to play a role in predicting prognosis early, which may possibly prevent TKA. We therefore hypothesized that the MRI findings on RA knees lower than LG II will give additional prediction on the severity of inflammation and chances of TKA. Methods We performed retrospective analysis on RA patients with knee complaints at our institution. Inclusion criteria include patients treated on Etanercept with knee symptoms and underwent MRI evaluation before Etanercept was initiated. We analyzed the relationship between baseline MRI findings (presence of synovitis, T1 low/T2 high) and the chances of having TKA despite Etanercept treatment. Results We identified total 116 RA patients on Etanercept, and TKA was performed in total 35 knee joints of 28 patients among them. TKA was performed in 12.3% of the patients in LG 0-II, and 45.5% in LG III, IV, which showed statistically significant difference (p<0.001). Those knee joints in LG0-II with MRI findings suggesting synovitis underwent TKA significantly more often than those without MRI findings (16.4%, 4.9%, p=0.0496). Similarly, baseline LG0-II joints with and without T1 low, T2 high signals showed statistical difference in the frequency of TKA (34.5% vs 0.0%, p<0.001) (Table 1). Table 1. The relationship between baseline MRI findings and the chance of having TKA (Larsen grade 0, I, II joints) w/ synovitis (110 joints*)w/o synovitis (41 joints*)p-value† Synovitis  TKA performed joints (%)18 (16.4)2 (4.9)0.0496 w/ signals (55 joints**)w/o signals (91 joints**)p-value† T1 low, T2 high signals  TKA performed joints (%)19 (34.5)0 (0.0)<0.001 *11 joints which have not any MRI data were expected. **16 joints which have not any MRI data were expected. †Tisher’s exact test. Conclusions Once the knee joint destruction progress to LG III and IV in RA patients with knee complaints, joint destruction continues and more often results in TKA. RA patients with knee complaints would be benefited from MRI evaluation before biologics treatment, even if the knee X-ray suggests LG0-II. If MRI suggests synovitis or T1 low, T2 high findings, the disease may progress to joint destruction. We advocate MRI is a necessary test in order to predict prognosis. We also advocate that Etanercept treatment needs to be initiated in the earliest stage possible, ide...