Former Olympians had remained on high bone mineral density for a long period: Consecutive checkup of the 1964 Tokyo Olympic Japanese contestants for over 50 years.

INTRODUCTION: We performed consecutive checkups of the 1964 Tokyo Olympic contestants every 4 years for 50 years. This study evaluated bone mineral density (BMD) and its related factors in former Tokyo Olympic athletes. OBJECTIVES: The study population comprised 181 former Olympians (141 men and 40 women) who had undergone BMD measurement in at least one of the four checkups performed every 4 years since 2005. The mean age of the 104 subjects who participated in the last checkup in 2016 was 76.1 years for men and 74.0 years for women. METHODS: Health-related information regarding medical history, regular physical activity, alcohol consumption, and smoking was obtained using questionnaires. The areal BMD of the total body was measured using dual-energy X-ray absorptiometry (DXA). The relationship between BMD and anthropometric measurements, medical history, and health behaviors was examined. Furthermore, we assessed the influence of the mode and magnitude of weight-bearing and impact loading during athletic events during their active careers on BMD. RESULTS: The mean Z-scores of BMD of the total body, lumbar spine, pelvis, and upper and lower limbs were > 0 in both male and female subjects at each checkup. The subjects had a higher mean height and weight than the Japanese age- and sex-matched individuals. Furthermore, the subjects had higher grip strength than the age- and sex-matched individuals. BMD showed a positive correlation with body weight, lean body mass (LBM), muscle mass, and grip strength, with higher correlation coefficients found between BMD of the pelvis or lower limbs and LBM or muscle mass volume. When the association with current participation in sports activities was examined, male subjects who exercised weekly had significantly higher grip strength and greater muscle mass volume; however, no significant differences were observed among female subjects. After adjusting for age and LMB, BMD was significantly higher in both the lumbar spine and lower limbs of male subjects with relatively more impact loading in sports events during their active careers. CONCLUSION: The Tokyo Olympic contestants maintained a high muscle mass even at an older age, regardless of their medical history, which may be one of the reasons for their ability to maintain a high BMD.

Type 1 Achilles tendon rupture caused by grooming trauma in a young dog.

Achilles tendon rupture is uncommon in small animal practice. A 9-month-old, female, mixed breed dog (weighing 2.2kg) was referred to our hospital with a primary complaint of right hind limb lameness. Complete right Achilles tendon rupture was diagnosed by physical examination and radiography. The tendon was surgically repaired the next day by using a three-loop and single near-far-far-near suture methods. Complete healing was achieved by 97 days post-surgery. This report describes the surgical technique used for complete Achilles tendon rupture repair in a young dog.

[Impact of preoperative 64-row multislice computed tomography for congenital aortic stenosis; report of a case].

A 63-year-old woman was diagnosed as having severe aortic stenosis (AS) with 98 mmHg peak pressure gradient detected by echocardiography. Since, preoperative enhanced 64-row multislice computed tomography (MSCT) showed bicuspid aortic valve with only 2 sinuses of Valsalva, congenital aortic stenosis was suspected. The left and right coronary arteries originated from respective sinus of Valsalva, and severely thickened cusps of aortic valve were detected clearly by preoperative 64-row MSCT. Aortic valve replacement with a 21 mm ATS mechanical bileaflet prosthesis was performed without aortic annulus enlargement. The postoperative course was uneventful and postoperative 64-row MSCT indicated good performance of the ATS valve. Preoperative 64-row MSCT could be useful to detect complex aortic valve disease in detail. Moreover. 64-row MSCT might be a reliable tool to evaluate valvular heart disease.

The post-operative changes in the level of inflammatory markers after posterior lumbar interbody fusion.

Inflammatory markers such as the C-reactive protein (CRP), white blood cell count and body temperature are easy to measure and are used as indicators of infection. The way in which they change in the early post-operative period after instrumented spinal surgery has not been reported in any depth. We measured these markers pre-operatively and at one, four, seven and 14 days postoperatively in 143 patients who had undergone an instrumented posterior lumbar interbody fusion. The CRP proved to be the only sensitive marker and had returned to its normal level in 48% of patients after 14 days. The CRP on day 7 was never higher than that on day 4. Age, gender, body temperature, operating time and blood loss were not related to the CRP level. A high CRP does not in itself suggest infection, but any increase after four days may presage infection.

A phase II study of cisplatin and docetaxel administered as three consecutive weekly infusions for advanced non-small-cell lung cancer in elderly patients.

BACKGROUND: To evaluate the efficacy and safety of treatments for advanced non-small-cell lung cancer in elderly patients aged 75 years or older, we conducted a phase II study of cisplatin and docetaxel administered in three consecutive weekly infusions. PATIENTS AND METHODS: The eligibility criteria for the study included the presence of chemotherapy-naive advanced non-small-cell lung cancer, age > or =75 years, Eastern Cooperative Oncology Group performance status of 0 or 1, a measurable lesion, adequate organ functions and signed informed consent. The chemotherapy regimen consisted of cisplatin (25 mg/m(2)) and docetaxel (20 mg/m(2)) on days 1, 8 and 15 every 4 weeks. RESULTS: Between February 2000 and March 2002, 34 elderly patients with non-small-cell lung cancer were enrolled in the study and 33 patients were treated. Two complete responses and 15 partial responses were obtained for an objective response rate of 52% in 33 treated patients. The median survival period was 15.8 months, and the 1-year survival rate was 64%. Toxicities were mild with no grade 4 toxicities. Only grade 3 leukopenia (6%), neutropenia (12%), anemia (3%), hyponatremia (3%) and nausea/vomiting (3%) were observed. CONCLUSION: Cisplatin and docetaxel administered in three consecutive weekly infusions was safe and effective for the treatment of elderly patients with chemotherapy-naive non-small-cell lung cancer.

Role of Notch-1 intracellular domain in activation of rheumatoid synoviocytes.

OBJECTIVE: Notch family proteins are transmembrane receptors that control cell fate and proliferation. Rheumatoid arthritis (RA) is characterized by activation and abnormal proliferation/differentiation of synoviocytes. We examined the expression of Notch-1 and its role in the activation of RA synoviocytes. METHODS: The expression of Notch-1 protein was detected by a specific antibody raised against the Notch-1 intracellular domain. Notch-1 messenger RNA (mRNA) expression in synoviocytes was analyzed by Northern blotting. Notch-1 protein expression was confirmed by Western blotting with anti-Notch-1 antibody. To analyze the role of Notch-1 in synoviocyte proliferation, we examined the effects of antisense Notch-1 oligonucleotides (ODNs) and MW167, a gamma-secretase inhibitor. RESULTS: Notch-1 protein and mRNA were detected in synovium from all study subjects. The nucleus of RA synoviocytes showed strong staining with anti-Notch-1 antibody, whereas there was predominantly cytoplasmic staining of normal and osteoarthritis (OA) synoviocytes. Western blotting showed a distinct approximately 63-kd protein detected by anti-Notch-1 antibody in nuclear extracts from RA synoviocytes, indicating that nuclear staining of RA synovium and synoviocytes is likely to be the result of nuclear localization of Notch-1 intracellular domain (NICD). Furthermore, tumor necrosis factor alpha (TNFalpha) increased NICD nuclear translocation in a dose-dependent manner. Antisense Notch-1 ODNs partially blocked the proliferation of RA synoviocytes and inhibited TNFalpha-induced proliferation in both OA and RA synoviocytes. In addition, gamma-secretase inhibitor, which blocks the production of NICD, also inhibited TNFalpha-induced proliferation of RA synoviocytes. CONCLUSION: Our results demonstrate the expression of Notch-1 in synoviocytes and the presence of Notch-1 fragment in the nuclei of RA synoviocytes and suggest the involvement of Notch-1 signaling in the TNFalpha-induced proliferation of RA synoviocytes.

Stromelysin-1 (MMP-3) in synovial fluid of patients with rheumatoid arthritis has potential to cleave membrane bound Fas ligand.

OBJECTIVE: To investigate the relationship between matrix metalloproteinases (MMP) and the soluble form of Fas ligand (sFasL) in the synovial fluid (SF) of patients with rheumatoid arthritis (RA), and to determine which MMP have a major role in cleaving FasL. METHODS: The concentrations of sFas and sFasL in SF from 48 patients with RA and 43 patients with osteoarthritis (OA) were measured using specific ELISA. The levels of different MMP (MMP-1, 2, 3, 7, 9) in SF were also measured by ELISA. The active forms of gelatinases were detected by gelatin zymogram. Human FasL-expressing transfected cells (hFasL/L5178Y) were used to investigate whether FasL is cleaved from membrane bound FasL. RESULTS: Significantly higher levels of MMP-1, 3, and 9 were found in SF from RA patients compared to OA patients, but MMP-7 was not detectable in either group. The concentrations of sFas and sFasL in SF were also higher in RA than in OA patients. However, there was no relationship between the concentration of sFas and sFasL. Among MMP, MMP-3 concentrations in SF were closely correlated with the level of sFasL and with disease activity of RA. Enzymatic cleavage assay indicated that MMP-3 has potential to cleave the FasL expressed on hFasL/L5178Y cells and to produce sFasL. CONCLUSION: There was significant correlation between the concentration of sFasL and MMP-3 in SF of patients with RA. In addition, our data indicate that the shedding of FasL may be regulated by MMP-3 in the joint of patients with RA.

Effects of combinations of anti-rheumatic drugs on the production of vascular endothelial growth factor and basic fibroblast growth factor in cultured synoviocytes and patients with rheumatoid arthritis.

OBJECTIVE: To examine whether different combinations of disease-modifying anti-rheumatic drugs (DMARDs), including bucillamine (BUC), gold sodium thiomalate (GST), methotrexate (MTX), salazosulphapyridine (SASP) and dexamethasone (DEX; a steroid), act by inhibiting the production of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in cultured synoviocytes, causing a decrease in their serum concentrations in patients with rheumatoid arthritis (RA). METHODS: The VEGF and bFGF concentrations in cultured synoviocytes and peripheral blood from patients with RA were measured by enzyme-linked immunosorbent assay and their serum concentrations were measured at two time points. RESULTS: BUC and GST inhibited VEGF production even when given alone, and a combination of BUC, GST and MTX with DEX also inhibited VEGF production. None of the DMARDs or DEX inhibited bFGF production when given alone, but a combination of SASP and GST inhibited the production of bFGF in cultured synoviocytes. Serum VEGF concentrations were significantly decreased 6 months after the commencement of medication compared with their concentrations before medication. CONCLUSION: Our results show that the effects of a combination of DEX with any two of BUC, GST, SASP and MTX on the production of VEGF and bFGF in cultured synoviocytes and on the serum concentrations of VEGF in patients with RA may be based on synergistic or additive effects of the drugs.

Effects of sulfhydryl compounds on interleukin-1-induced vascular endothelial growth factor production in human synovial stromal cells.

We investigated the effects of various sulfhydryl compounds on interleukin-1 (IL-1)-induced vascular endothelial growth factor (VEGF) production in human synovial stromal cells (HSSC). HSSC stimulated by IL-1beta (100 ng/ml) produced VEGF and interleukin-6 (IL-6) in vitro. Monosulfhydryl compounds, N-acetylcysteine, D-penicillamine, tiopronin and the bucillamine-like disulfhydryl compound, compound A scarcely affected VEGF or IL-6 production at concentrations of 10(-5) and 10(-4) M. However, the disulfhydryl compound, bucillamine inhibited VEGF production but not IL-6 production at concentrations of 10(-5) and 10(-4) M. These results suggest that bucillamine may be a selective inhibitor of IL-1-induced VEGF production in HSSC, and that inhibition of VEGF production may require not only SH groups but also a specific chemical structure.

Isolation of calcifiable vesicles from aortas of rabbits fed with high cholesterol diets.

Advanced arterial wall calcification in atherosclerosis imposes a serious rupturing effect on the aorta. However, the mechanism of dystrophic calcification linked to hyperlipidemia, that causes atherosclerosis remains unknown. Emerging morphological and biochemical evidence reveals that calcifiable vesicles may have a role in plaque calcification. To determine whether a high cholesterol diet can induce arterial calcification and produce or activate calcifiable vesicles in aortas, a rabbit model was used. After 2 months of daily high lipid feeding (supplemented with 2% cholesterol and 6% peanut oil), typical atherosclerotic lesions developed. However, the mineral, if present in aortas, was insufficient to be detected by Fourier transform-infrared spectroscopy (FT-IR) or alizarin red staining, indicative of a non-calcifying stage of atherosclerosis. Small segments of thoracic aortas were digested in a crude collagenase solution to release calcifiable vesicles. Vesicles were also isolated from normal aortas as control to consider the possibility that membrane vesicles may be produced by crude collagenase digestion, which could cause the degradation of some cells. Calcifiable vesicles were precipitated at 300,000 x g after subcellular particles were removed by centrifugation at 30,000 x g. Calcifiability of isolated vesicles was then tested using calcifying media containing physiological levels of Ca2+ and Pi and 1 mM ATP. Electron microscopic observations showed that the isolated vesicles were heterogeneous in size and shape and capable of depositing electron dense particles. Fourier transform infrared spectroscopic analysis of the deposited particles revealed the presence of an amorphous mineral phase. The spectroscopic mineral to matrix ratios, related to the amount of mineralization, indicated that vesicles from cholesterol-fed rabbits produced more minerals than control vesicles obtained from the normal aortas. Alizarin red staining for mineral further demonstrated substantially higher calcifiability of the experimental vesicles. A 3-5 h exposure of the vesicles to calcifying media caused significant deposition of 45Ca and 32Pi in a vesicle protein-concentration dependent manner. Similar to previously reported observations with human atherosclerotic aorta vesicles, rabbit vesicles were enriched in ATP-hydrolyzing enzymes including Mg2+- or Ca2+-ATPase and NTP pyrophosphohydrolase that are implicated in normal and pathological calcification. Altogether, these observations suggest that accumulation of the released calcifiable vesicles, as a result of high cholesterol diets, may have a role in dystrophic calcification in hyperlipidemia-related atherosclerosis.

Inhibitory effects of anti-rheumatic drugs on vascular endothelial growth factor in cultured rheumatoid synovial cells.

Vascular endothelial growth factor (VEGF) is a potent inducer of angiogenesis and is constitutively expressed in the synovium of rheumatoid arthritis (RA). Over-expression of VEGF may play an important role in pathogenic vascularization and synovial hyperplasia of RA. In the present study, we examined whether disease-modifying anti-rheumatic drugs (DMARDs), including bucillamine (BUC), gold sodium thiomalate (GST), methotrexate (MTX) and salazosulfapiridine (SASP), act by inhibiting the production of VEGF by cultured synovial cells of patients with RA. Treatment of cultured synoviocytes with lipopolysaccharide (LPS) significantly increased VEGF production by cultured synovial cells. BUC significantly inhibited LPS-induced VEGF production, while GST tended to inhibit the production of VEGF. The inhibitory effects on VEGF production were dose-dependent. In contrast, MTX and SASP did not affect VEGF production. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis showed that BUC also inhibited LPS-induced VEGF mRNA expression in RA synovial cells. The present study provides the first evidence that BUC inhibits VEGF production and the expression of its mRNA in synovial cells of RA patients. Our results indicate that the anti-rheumatic effects of BUC are mediated by suppression of angiogenesis and synovial proliferation in the RA synovium through the inhibition of VEGF production by synovial cells.

Efficacy of all-trans retinoic acid for molecular relapse of acute promyelocytic leukemia during remission.

We analyzed the efficacy of all-trans retinoic acid (ATRA) as an early treatment for four acute promyelocytic leukemia (APL) patients in remission who were PML/RARalpha-positive by reverse transcription-polymerase chain reaction or fluorescence in situ hybridization. ATRA 45 mg/m2 was administered orally. All became negative for PML/RARalpha transcripts after 3 to 6 months of ATRA treatment. However, the PML/RARalpha transcripts subsequently reverted to positive in three cases. Although retreatment with ATRA failed to prevent hematological relapse in two patients, one case remains in hematological remission. No serious side effects were encountered during ATRA treatment. These findings suggest that early treatment of ATRA for PML/RARalpha-positive APL patients in remission may have a therapeutic benefit and prolong the duration of hematological remission without chemotherapy.

Effects of bucillamine and N-acetyl-L-cysteine on cytokine production and collagen-induced arthritis (CIA).

We investigated the effects of bucillamine and N-acetyl-L-cysteine (NAC) on cytokine production and CIA. Bucillamine and NAC inhibited NF-kappaB activation and tumour necrosis factor-alpha (TNF-alpha) mRNA expression in human monocytic leukaemia cell line THP-1, and cytokine production from monocyte cell lines at concentrations >10-3 M. They also inhibited cytokine production and CIA in mice at a dose of 500 mg/kg. These results suggest that NF-kappaB inhibitors such as bucillamine and NAC may inhibit cytokine-related diseases, including arthritis.

Extracellular human T cell leukemia virus type I tax protein stimulates the proliferation of human synovial cells.

OBJECTIVE: The present study was designed to investigate whether the proliferation of normal synovial cells from patients with meniscus injury is stimulated by human T cell leukemia virus type I (HTLV-I) Tax protein. METHODS: The effect of Tax protein on the proliferation of synovial cells was evaluated using a 3H-thymidine incorporation assay. Production of cytokines was determined by enzyme-linked immunosorbent assay. Nuclear factor kappaB (NF-kappaB) DNA binding activity and the transcription of several NF-kappaB-mediated genes was detected by electrophoretic mobility shift assay and reverse transcriptase-polymerase chain reaction. RESULTS: The proliferation of synovial cells, as well as their expression of tumor necrosis factor alpha, granulocyte-macrophage colony-stimulating factor, and interleukin-6, was significantly enhanced by extracellular Tax at concentrations of 2.5 pM to 25 nM. In contrast, extracellular bacterial extract did not change the cytokine expression or the proliferation of these cells. Proliferation of synovial cells induced by Tax protein may be due to activated expression of several cytokines and protooncogenes that contain NF-kappaB regulatory sequences. CONCLUSION: Our results suggest that extracellular Tax can regulate the expression of endogenous cellular genes in synovial cells and may contribute to the NF-kappaB-mediated synovial hyperplasia.

Characterisation of fibroblast-like cells in pannus lesions of patients with rheumatoid arthritis sharing properties of fibroblasts and chondrocytes.

OBJECTIVE: To better understand the characteristics of synoviocytes located in the rheumatoid arthritis (RA) pannus. METHODS: One cell line, termed PSC, was cloned from RA pannus lesions. Phenotypic analysis was done by contrast microscopy, indirect immunostaining, and safranin O staining. Transcription of several protooncogenes and matrix degrading enzymes was evaluated. The expression of mRNA for collagen II was detected by in situ hybridisation. The ability of anchorage independent growth was assessed by soft agarose culture. RESULTS: PSCs showed a high transcription of protooncogenes c-fos, c-myc and c-jun. They also expressed mRNA for matrix degrading enzymes, such as collagenase, cathepsin B, and cathepsin L. Anchorage independent growth assay demonstrated that PSCs formed colonies in soft agar culture. Phenotypic analysis showed that this fibroblast-like PSC was stained intensely with anti-vimentin and anti-fibroblast antibody. In situ reverse transcriptase assay showed that the cell line expressed type II collagen mRNA. CONCLUSION: Alternative fibroblast-like cells were identified in the pannus lesion of RA sharing properties of fibroblasts and chondrocytes. These findings suggest that this fibroblast-like cell derived from pannus lesions may contribute to the destruction of the cartilage in RA.

Tenosynovial nodulosis in a patient infected with human T cell lymphotropic virus I.

We describe a 45-year-old man who presented with multiple nodules along the tendons of the scapular region, the elbows, wrists, forearms, thighs, and ankles. The patient was a carrier of human T cell lymphotropic virus I (HTLV-I), which was probably transmitted from his mother; his mother also had polyarthritis. Histopathologically, the nodules consisted of numerous, small, fibrinoid masses. The synovium adjacent to the tendon sheath was hyperplastic, with fibrinoid necrosis mimicking rheumatoid synovium. However, synovitis was not present inside the adjacent joint. HTLV-I proviral DNA was detected in the cells of the nodule, in tenosynovial cells, and in peripheral blood lymphocytes, but not in skin fibroblasts. In situ reverse transcription assay showed a high quantity of tax/rex messenger RNA in the proliferating lining cells. Based on these features, we classified this case as an atypical manifestation of HTLV-I-associated arthropathy associated with fibrinoid nodules resulting from chronic tenosynovitis.

Accumulation of soluble Fas in inflamed joints of patients with rheumatoid arthritis.

OBJECTIVE: To examine the concentration of the soluble form of the Fas molecule (sFas) in the serum and synovial fluid of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: The concentration of sFas in the serum of 15 normal subjects and in the synovial fluid and serum of 45 RA patients and 13 OA patients was determined. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and the level of several cytokines in serum and synovial fluid were also determined. RESULTS: The synovial fluid concentration of sFas was higher in RA than in OA patients (P < 0.005). The synovial fluid level of sFas correlated weakly with serum levels of CRP (r = 0.541), the ESR (r = 0.499), and with synovial fluid levels of interleukin-2 (IL-2) receptor (r = 0.544), IL-6 (r = -0.529), and intercellular adhesion molecule 1 (r = 0.514). Reverse transcription-polymerase chain reaction analysis revealed that synovial cells and infiltrating mononuclear cells expressed sFas messenger RNA in RA patients. CONCLUSION: Our data suggest that accumulation of sFas in the joint cavity of RA patients may inhibit apoptosis and exacerbate the inflammatory process.

Prevalence of risk factors for coronary heart disease among Dominicans in the Dominican Republic: comparison with Japanese and Americans using existing data.

Risk factors of coronary heart disease (CHD) in Dominicans were compared with those of Japanese and Americans for the presumption of prevalence of CHD in about 2000 persons. Dominican adults aged 20 through 76 years were medically examined in 1993. Data of nationally representative Japanese and Americans which included serum lipid levels were compared. Total cholesterol levels(TCH) in Dominicans were lower than those in Americans. High-density lipoprotein cholesterol levels in Dominicans were lower than those in Japanese and Americans. The prevalence of hypertension and current smoking rates in Dominicans were similar to that of Americans and lower than that of Japanese. TCH in Americans have substantially been declining and those in Japanese were inadequate for preventing CHD. The prevalence of CHD in Dominicans may be lower than that of Americans viewed from the recent levels of main risk factors. Community wide health programs have spread to people with hypertension a decrease in the incidence of CHD should occur.

Induction of Fas-dependent apoptosis in synovial infiltrating cells in rheumatoid arthritis.

Apoptosis is a feature of the synovium of rheumatoid arthritis (RA). We have recently shown that RA synoviocytes were susceptible to anti-Fas mAb and undergo apoptosis in vitro. To investigate whether infiltrating mononuclear cells also undergo Fas-dependent apoptosis, double-labeling techniques combined with immunohistochemical examination with anti-CD3 mAb and the TdT-mediated dUTP-blotin nick end labeling (TUNEL) method to detect apoptotic cells, or in situ RT assay to detect Fas mRNA, were performed using frozen tissue sections. We also examined the in vitro induction of Fas-dependent apoptosis in freshly isolated synovium infiltrating mononuclear cells (SIM), synovial stromal cells (SSC) and peripheral blood lymphocytes (PBL) using tissues from nine patients with RA and three with osteoarthritis (OA). The results showed expression of Fas antigen and apoptotic cells in a number of CD3-bearing cells in RA synovial tissues. In vitro treatment with anti-Fas mAb produced a significant apoptosis of RA SIM and SSC, while none of PBL, and neither SIM nor SSC from OA exhibited apoptosis. Moreover, approximately 50% of CD4+, CD3+ and CD45RO+ cells, and > 90% of Fas-expressing cells of RA SIM underwent apoptosis in response to anti-Fas mAb, as detected by flow cytometry. Our results suggest that RA synovial infiltrating lymphocytes acquire high susceptibility to anti-Fas mAb and undergo apoptosis. Such a phenomenon of infiltrating T cells in RA synovium may play an important pathophysiological role and suggest a possible therapeutic effect for anti-Fas mAb in RA.

Novel mechanisms of selective apoptosis in synovial T cells of patients with rheumatoid arthritis.

OBJECTIVE: To analyze whether T cells infiltrating the synovium of patients with rheumatoid arthritis (RA) express functional Fas antigen. METHODS: Mononuclear T cells, mainly from synovial tissues, synovial fluids (SF), and peripheral blood mononuclear cells (PBMC) from 14 patients with RA and 5 with osteoarthritis (OA), were treated with anti-Fas monoclonal antibody (Mab) (CH11) for 24 h in vitro. Cell viability and DNA fragmentation were examined. The expression of Fas antigen, Fas ligand, and T cell subpopulations was examined using flow cytometry and reverse transcription polymerase chain reaction. RESULTS: More than 50% of T cells from synovial tissue and SF of patients with RA underwent apoptosis, whereas no effect was observed in PBMC from RA or PBMC and synovial T cells from OA, suggesting that functional Fas antigens are specifically expressed on synovial T cells. Flow cytometric analysis demonstrated higher expression of Fas antigen in T cells from RA synovium than from PBMC. The T cell subpopulations susceptible to anti-Fas Mab were mainly CD45RO+ and CD4 or CD8 single positive T cells, indicating that activated mature T cells express functional Fas antigen. Fas ligand was overexpressed only in synovial nonadherent cells in RA at the level of mRNA, whereas T cells account for more than 60% of the total, but not in OA. CONCLUSION: These findings suggest the majority of activated T cells infiltrating the synovium express functional Fas antigen and Fas ligand specifically in patients with RA but not OA. This phenomenon may provide a clue to understanding the pathogenesis of RA.