19 results on '"Takehara, Kazuhiko"'
Search Results
2. Serum CXCL16 Concentrations Correlate with the Extent of Skin Sclerosis in Patients with Systemic Sclerosis
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YANABA, KOICHI, MUROI, EIJI, YOSHIZAKI, AYUMI, HARA, TOSHIHIDE, OGAWA, FUMIHIDE, SHIMIZU, KAZUHIRO, YOZAKI, MARIKO, HASEGAWA, MINORU, FUJIMOTO, MANABU, TAKEHARA, KAZUHIKO, and SATO, SHINICHI
- Abstract
OBJECTIVE: To determine serum concentrations of soluble CXCL16 and its clinical associations in patients with systemic sclerosis (SSc). METHODS: Serum CXCL16 levels from 89 patients with SSc were examined by ELISA. In a retrospective longitudinal study, 68 sera from 28 patients with SSc were analyzed (followup 1.3 to 7.3 yrs). RESULTS: Serum CXCL16 levels were elevated in patients with SSc compared with healthy controls (n = 42). Patients with diffuse cutaneous SSc (n = 52) had higher levels of CXCL16 than those with limited cutaneous SSc (n = 37). Serum CXCL16 levels correlated positively with the extent of skin sclerosis. In the longitudinal study, CXCL16 levels generally decreased on a parallel with the improvement in skin sclerosis. CONCLUSION: CXCL16 levels were increased in patients with SSc, and correlated with the extent of skin sclerosis, suggesting that CXCL16 may have a role in the development of skin fibrosis in SSc. Blockade of CXCL16 interaction might be a potential therapeutic target in patients with SSc.
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- 2009
3. Elevated Circulating TWEAK Levels in Systemic Sclerosis: Association with Lower Frequency of Pulmonary Fibrosis
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YANABA, KOICHI, YOSHIZAKI, AYUMI, MUROI, EIJI, HARA, TOSHIHIDE, OGAWA, FUMIHIDE, USUI, AYA, HASEGAWA, MINORU, FUJIMOTO, MANABU, TAKEHARA, KAZUHIKO, and SATO, SHINICHI
- Abstract
OBJECTIVE: To determine serum levels of tumor necrosis factor-related weak inducer of apoptosis (TWEAK) and its clinical associations in patients with systemic sclerosis (SSc). METHODS: Serum TWEAK levels from 70 patients with SSc were examined by ELISA. In a retrospective longitudinal study, sera from 23 patients with SSc were analyzed (followup 0.8–7.2 yrs). RESULTS: Serum TWEAK levels were elevated in patients with SSc (n = 70) compared with healthy controls (n = 31) and patients with systemic lupus erythematosus (n = 22). Among patients with SSc, there were no differences in serum TWEAK levels between limited cutaneous SSc and diffuse cutaneous SSc. Patients with SSc who had elevated TWEAK levels less often had pulmonary fibrosis and decreased vital capacity than those with normal TWEAK levels. In the longitudinal study, SSc patients with inactive pulmonary fibrosis or without pulmonary fibrosis consistently exhibited increased TWEAK levels, while those with active pulmonary fibrosis showed decreased TWEAK levels during the followup period. CONCLUSION: TWEAK levels were increased in patients with SSc, and associated with a lower frequency of pulmonary fibrosis in patients with SSc. TWEAK could be a protective factor against the development of pulmonary fibrosis in this disease and as such would be a possible therapeutic target.
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- 2009
4. Increased Serum Pentraxin 3 in Patients with Systemic Sclerosis
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IWATA, YOHEI, YOSHIZAKI, AYUMI, OGAWA, FUMIHIDE, KOMURA, KAZUHIRO, HARA, TOSHIHIDE, MUROI, EIJI, TAKENAKA, MOTOI, SHIMIZU, KAZUHIRO, HASEGAWA, MINORU, FUJIMOTO, MANABU, TAKEHARA, KAZUHIKO, and SATO, SHINICHI
- Abstract
OBJECTIVE: To determine serum concentrations of pentraxin 3 (PTX3) and its clinical associations in patients with systemic sclerosis (SSc). METHODS: Serum PTX3 levels from 45 patients with diffuse cutaneous SSc (dSSc), 46 with limited cutaneous SSc (lSSc), and 20 healthy controls were examined by ELISA. PTX3 expression in the sclerotic skin from SSc patients was evaluated immunohistochemically. Normal and SSc fibroblasts were cultured and PTX3 levels in the culture medium were also examined by ELISA. RESULTS: Serum PTX3 levels were elevated in patients with SSc relative to controls. PTX3 levels in dSSc patients were significantly higher than in controls and lSSc patients. PTX3 expression in the sclerotic skin from SSc patients was more intense relative to normal skin. Elevation of serum PTX3 levels was associated with more frequent presence of pulmonary fibrosis, cardiac disease, and pitting scar/ulcer and increased serum immunoglobulin levels and erythrocyte sedimentation rates. PTX3 levels correlated positively with modified Rodnan total skin thickness score, and negatively with percentage vital capacity and percentage DLCO in patients with SSc. PTX3 levels also correlated positively with serum levels of 8-isoprostane, a marker of oxidative stress, and hyaluronan, recently identified as an endogenous ligand for Toll-like receptors. PTX3 production from cultured SSc fibroblasts was increased by stimulation with hyaluronan. CONCLUSION: These results suggest that elevated serum PTX3 levels are associated with the disease severity of SSc.
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- 2009
5. Elevated Serum Insulin-like Growth Factor (IGF-1) and IGF Binding Protein-3 Levels in Patients with Systemic Sclerosis: Possible Role in Development of Fibrosis
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Hamaguchi, Yasuhito, Fujimoto, Manabu, Matsushita, Takashi, Hasegawa, Minoru, Takehara, Kazuhiko, and Sato, Shinichi
- Abstract
OBJECTIVE: To examine serum concentrations of insulin-like growth factor (IGF-1) and IGF binding protein (IGFBP-3), a major carrier protein for IGF-1, in patients with systemic sclerosis (SSc); and to relate the results to clinical features in SSc. METHODS: Serum IGF-1 and IGFBP-3 levels in 92 Japanese patients with SSc were measured by ELISA. Expression of IGF-1 and IGFBP-3 messenger RNA (mRNA) in the skin was quantified by real-time reverse transcription-polymerase chain reaction. RESULTS: Serum IGF-1 and IGFBP-3 levels were significantly elevated in patients with SSc compared with patients with systemic lupus erythematosus or healthy controls. IGF-1 levels were higher in patients with diffuse cutaneous SSc (dcSSc) than in patients with limited cutaneous SSc (lcSSc). Patients with increased IGF-1 levels had more severe skin involvement and pulmonary fibrosis. IGF-1 mRNA was upregulated in the affected skin of patients with SSc. There were no significant differences in serum IGFBP-3 levels between dcSSc and lcSSc. IGFBP-3 levels were not associated with skin thickness and pulmonary fibrosis. Patients with increased IGF-1 or IGFBP-3 had lower frequency of telangiectasia than patients with normal levels. CONCLUSION: These results suggest that both IGF-1 and IGFBP-3 are involved in the development of SSc. The role of IGF-1 appears to be different from that of IGFBP-3.
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- 2008
6. Increased Serum Soluble OX40 in Patients with Systemic Sclerosis
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Komura, Kazuhiro, Yoshizaki, Ayumi, Kodera, Masanari, Iwata, Yohei, Ogawa, Fumihide, Shimizu, Kazuhiro, Wayaku, Takamasa, Yukami, Toru, Murata, Maki, Hasegawa, Minoru, Fujimoto, Manabu, Takehara, Kazuhiko, and Sato, Shinichi
- Abstract
OBJECTIVE: .To determine levels of serum soluble OX40 (also termed CD134, a member of the tumor necrosis factor receptor superfamily) and their clinical associations in patients with systemic sclerosis (SSc). METHODS: Serum soluble OX40 levels were examined by ELISA in 53 patients with SSc, 15 patients with systemic lupus erythematosus (SLE), and 32 healthy individuals. RESULTS: OX40 levels were significantly elevated in SSc patients (125.7 ± 5.7 pg/ml) compared to patients with SLE (80.7 ± 1.7 pg/ml; p < 0.005) and controls (88.2 ± 3.0 pg/ml; p < 0.0001). Elevated OX40 levels were found to be associated with disease duration of less than 2 years (p < 0.05). CONCLUSION: Our results suggest that serum soluble OX40 levels correlate with the early-onset of SSc disease.
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- 2008
7. Increased Serum Interleukin 23 in Patients with Systemic Sclerosis
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Komura, Kazuhiro, Fujimoto, Manabu, Hasegawa, Minoru, Ogawa, Fumihide, Hara, Toshihide, Muroi, Eiji, Takehara, Kazuhiko, and Sato, Shinichi
- Abstract
OBJECTIVE: The relationship between systemic sclerosis (SSc) and interleukin 23 (IL-23), a cytokine associated with the differentiation of T lymphocytes, is unknown. We investigated serum IL-23 levels and their clinical association in patients with SSc. METHODS: Serum IL-23 levels were examined by ELISA in 63 patients with SSc, 15 patients with systemic lupus erythematosus (SLE), and 31 healthy individuals. SSc patients comprised 25 with limited cutaneous SSc and 38 with diffuse cutaneous SSc. RESULTS: Serum IL-23 levels were significantly elevated in SSc patients compared to patients with SLE (p < 0.05) and controls (p < 0.005). Elevated serum IL-23 levels were associated with the disease duration (p < 0.05) and the prevalence of pulmonary fibrosis (p < 0.05), although they were not associated with other clinical features, including the extent of skin sclerosis or the severity of pulmonary fibrosis. CONCLUSION: The results suggest that IL-23 is associated with induction of SSc and that blockade of IL-23 can be a potential therapeutic strategy in early SSc.
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- 2008
8. Elevated Serum APRIL Levels in Patients with Systemic Sclerosis: Distinct Profiles of Systemic Sclerosis Categorized by APRIL and BAFF
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Matsushita, Takashi, Fujimoto, Manabu, Hasegawa, Minoru, Tanaka, Chihiro, Kumada, Sayako, Ogawa, Fumihide, Takehara, Kazuhiko, and Sato, Shinichi
- Abstract
OBJECTIVE: Elevated serum concentrations of B cell-activating factor belonging to the tumor necrosis factor family (BAFF) are found in systemic sclerosis (SSc) and are associated with the severity of skin sclerosis. We investigated serum levels of a proliferation-inducing ligand (APRIL), a close homolog to BAFF, and its clinical association in patients with SSc as well as its correlation with BAFF. METHODS: Serum APRIL levels from 74 patients with SSc, 25 patients with systemic lupus erythematosus, and 25 healthy subjects were examined by ELISA. Clinical and laboratory measures were compared between SSc patients with elevated serum APRIL levels and those with normal levels. We assessed correlation of serum APRIL and BAFF levels in patients with SSc. RESULTS: Serum APRIL levels were elevated in SSc patients compared to controls. SSc patients with elevated serum APRIL levels had significantly higher incidences of pulmonary fibrosis than those with normal levels. Serum APRIL levels did not correlate with serum BAFF levels in SSc patients, and there were distinct profiles of SSc categorized by serum APRIL and BAFF levels. High APRIL levels served as a marker for involvement of pulmonary fibrosis and high BAFF levels served as a marker for severe skin sclerosis. CONCLUSION: The results suggest that elevated serum APRIL and BAFF levels were differentially associated with disease severity in SSc.
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- 2007
9. Clinical Evaluation of Anti-Aminoacyl tRNA Synthetase Antibodies in Japanese Patients with Dermatomyositis
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Matsushita, Takashi, Hasegawa, Minoru, Fujimoto, Manabu, Hamaguchi, Yasuhito, Komura, Kazuhiro, Hirano, Takashi, Horikawa, Mayuka, Kondo, Miki, Orito, Hidemitsu, Kaji, Kenzo, Saito, Yuki, Matsushita, Yukiyo, Kawara, Shigeru, Yasui, Masahide, Seishima, Mariko, Ozaki, Shoichi, Kuwana, Masataka, Ogawa, Fumihide, Sato, Shinichi, and Takehara, Kazuhiko
- Abstract
OBJECTIVE: To investigate the distribution of anti-aminoacyl-tRNA synthetase (anti-ARS) antibodies among patients with autoimmune diseases, and to analyze the clinical features of patients with dermatomyositis (DM) with anti-ARS antibodies. METHODS: Serum samples from 315 patients with autoimmune diseases or related disorders who had visited Kanazawa University Hospital or affiliated facilities were assessed for anti-ARS antibodies by immunoprecipitation. In particular, the association between anti-ARS antibodies and clinical features was investigated in detail in patients with DM. RESULTS: Anti-ARS antibody was positive in 16 (29%) of 55 patients with DM, 2 (22%) of 9 patients with polymyositis, and 7 (25%) of 28 patients with idiopathic pulmonary fibrosis. Although anti-ARS antibody was detected with high frequency (63%, 15/24) in DM patients with interstitital lung disease (ILD), the incidence of anti-ARS antibody was very low (3%, 1/31) in DM patients without ILD. Anti-ARS antibody-positive patients with DM had significantly higher incidences of ILD (94% vs 23%) and fever (64% vs 10%) than the antibody-negative patients. Some immunosuppressive agents, in addition to oral corticosteroids, were required more frequently in the antibody-positive patients with DM than the antibody-negative patients (88% vs 26%). Although 60% of DM patients with ILD simultaneously developed ILD and myositis, ILD preceded myositis in 33% of patients. CONCLUSION: Among patients with DM, anti-ARS antibodies are found in a subset with ILD. DM patients with anti-ARS antibodies appear to have a more persistent disease course that requires additional therapy compared to those without anti-ARS antibodies.
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- 2007
10. Increased Serum Soluble CD40 Levels in Patients with Systemic Sclerosis
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Komura, Kazuhiro, Fujimoto, Manabu, Matsushita, Takashi, Yanaba, Koichi, Kodera, Masanari, Kawasuji, Ayako, Hasegawa, Minoru, Takehara, Kazuhiko, and Sato, Shinichi
- Abstract
OBJECTIVE: To determine serum levels of soluble CD40 (sCD40) and clinical association in patients with systemic sclerosis (SSc). METHODS: Serum sCD40 levels were examined by ELISA in 49 patients with SSc, 15 patients with systemic lupus erythematosus, and 26 healthy individuals. sCD40 levels in plasma samples, which were obtained at the same time, were also determined. SSc patients were grouped into 22 patients with limited cutaneous SSc (lcSSc) and 27 patients with diffuse cutaneous SSc (dcSSc). RESULTS: There was no significant difference between sCD40 levels of sera and those of plasma. Serum sCD40 levels were significantly elevated in patients with SSc compared to patients with systemic lupus erythematosus and controls (p < 0.001). Serum sCD40 levels were higher in patients with lcSSc than in those with dcSSc (p <0.001). There was no correlation between sCD40 and sCD40 ligand levels in patients with SSc. CONCLUSION: Elevated serum sCD40 levels were associated with lcSSc. These results suggest that the blockade of CD40/CD40 ligand interaction could be a potential therapeutic strategy in SSc.
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- 2007
11. The Efficacy of Self-Administered Stretching for Finger Joint Motion in Japanese Patients with Systemic Sclerosis
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Mugii, Naoki, Hasegawa, Minoru, Matsushita, Takashi, Kondo, Miki, Orito, Hidemitsu, Yanaba, Koichi, Komura, Kazuhiro, Hayakawa, Ikuko, Hamaguchi, Yasuhito, Ikuta, Munehiro, Tachino, Katsuhiko, Fujimoto, Manabu, Takehara, Kazuhiko, and Sato, Shinichi
- Abstract
OBJECTIVE: To determine the efficacy of self-administered stretching of each finger in Japanese patients with systemic sclerosis (SSc). METHODS: Forty-five patients with SSc (32 with diffuse cutaneous SSc and 13 with limited cutaneous SSc) were given instructions on self-administered stretching and were directed to perform it every day. Individual fingers were maintained in a stretched position using the opposite hand for 10 seconds and this was repeated 3–10 times. To evaluate the effect of the stretching program, finger passive range of motion (ROM) was assessed using a goniometer on the first visit and after 1 month and 1 year of the stretching program. The Health Assessment Questionnaire (HAQ) was also assessed on the first visit and 1 year afterward. RESULTS: The total passive ROM was significantly improved in each finger after 1 month of finger stretching. The total passive ROM was further improved or maintained within 1 year after the first visit. Although ROM was less in patients with diffuse cutaneous SSc than in those with limited cutaneous SSc at the first visit, ROM increased significantly irrespective of disease duration or severity of skin sclerosis. Finger stretching may improve the finger function, since the HAQ score for hand functions such as eating and gripping was significantly decreased. CONCLUSION: Our original self-administered stretching program may be useful for improving finger joint motion in patients with SSc; future studies in various ethnic populations will be needed to determine the universal efficacy of this method.
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- 2006
12. Longitudinal Analysis of Serum Cytokine Concentrations in Systemic Sclerosis: Association of Interleukin 12 Elevation with Spontaneous Regression of Skin Sclerosis
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Matsushita, Takashi, Hasegawa, Minoru, Hamaguchi, Yasuhito, Takehara, Kazuhiko, and Sato, Shinichi
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OBJECTIVE: Skin sclerosis that progresses in the earlier disease phase in systemic sclerosis (SSc) spontaneously regresses thereafter. We investigated the relationship between changes of the serum cytokine profile and changes in skin fibrosis in patients with SSc. METHODS: Serum cytokine levels were examined by ELISA using 180 sera samples from 26 patients with early diffuse cutaneous SSc (dcSSc) with mean disease duration of 2.1 years. The mean followup period was 4.9 years (range 2–8). Cytokine mRNA expression in the affected skin was quantified by real-time reverse transcription-polymerase chain reaction. RESULTS: Modified Rodnan total skin thickness score decreased after 2, 4, and 6 years compared to that at first visit. Serum levels of the Th2 cytokines interleukin 6 (IL-6) and IL-10 and monocyte chemotactic protein-1 (MCP-1) were higher at first evaluation compared to healthy controls, while IL-4 levels were normal. Levels of all Th2 cytokines generally decreased as skin sclerosis regressed. Conversely, levels of serum IL-12, a Th1-inducing cytokine, were lower at first visit relative to controls, but increased by roughly 15-fold after 6 years to significantly higher levels than controls. Surviving dcSSc patients exhibited elevated IL-12 levels compared to deceased patients. Serum levels of transforming growth factor-ß1 (TGF-ß1), a fibrogenic cytokine, increased throughout followup, with slightly decreased levels at later timepoints. IL-12 mRNA expression was upregulated in affected skin from patients with late-stage dcSSc, while TGF-ß1 and MCP-1 expression was downregulated. CONCLUSION: These results suggest that a shift from Th2 to Th1 response correlates with improvement in skin fibrosis in SSc, and that IL-12 level is a serologically useful marker for disease activity and prognosis.
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- 2006
13. Clinical Characteristics of Juvenile Systemic Sclerosis in Japanese
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Murata, Maki, Sato, Shinichi, KOMURA, KAZUHIRO, SHIRASAKI, FUMIAKI, HASEGAWA, MINORU, and TAKEHARA, KAZUHIKO
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- 2005
14. Anti-Lipoprotein Lipase Antibody in Systemic Sclerosis: Association with Elevated Serum Triglyceride Concentrations
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Kodera, Masanari, Hayakawa, Ikuko, Komura, Kazuhiro, Yanaba, Koichi, Hasegawa, Minoru, Takehara, Kazuhiko, and Sato, Shinichi
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OBJECTIVE: The vascular damage systemic sclerosis (SSc) consists mainly of microvascular changes, but recently macrovascular changes with dyslipidemia were recognized. In systemic lupus erythematosus (SLE), autoantibody to lipoprotein lipase (LPL), a key enzyme that hydrolyzes triglycerides, suggested a role of autoimmunity for elevated serum triglyceride levels and atherosclerosis. We investigated the prevalence and levels of anti-LPL antibodies, their clinical correlation, and their functional significance in patients with SSc. METHODS: Serum samples from patients with diffuse cutaneous SSc (dSSc; n = 55), limited cutaneous SSc (lSSc; n = 75), SLE (n = 21), and dermatomyositis (DM; n = 21) and healthy controls (n = 41) were examined by ELISA. The presence of anti-LPL antibody was evaluated by immunoblotting analysis using purified LPL. To determine the functional relevance of anti-LPL antibody in vivo, we assessed whether anti-LPL autoantibody was able to inhibit LPL activity using the LPL activity kit. RESULTS: ELISA revealed that IgG or IgM anti-LPL antibodies were detected in 35% of SSc patients, while they were also positive in 67% of SLE patients and 43% of DM patients. The presence of IgG anti-LPL antibody was associated with elevated serum triglyceride levels, greater extent of skin fibrosis, and more frequent presence of lung fibrosis, heart involvement, and anti-topoisomerase I antibodies. The presence of anti-LPL autoantibody was confirmed by immunoblotting analysis. LPL activity was inhibited by IgG anti-LPL antibodies in sera from SSc patients with elevated serum triglyceride levels. CONCLUSION: Our results suggest that anti-LPL autoantibody contributes to elevated serum triglyceride levels by inhibiting LPL enzyme activity in patients with SSc.
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- 2005
15. Comparative Study of Serum Surfactant Protein-D and KL-6 Concentrations in Patients with Systemic Sclerosis as Markers for Monitoring the Activity of Pulmonary Fibrosis
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Yanaba, Koichi, Hasegawa, Minoru, Takehara, Kazuhiko, and Sato, Shinichi
- Abstract
OBJECTIVE: To clarify the clinical significance of surfactant protein-D (SP-D) and KL-6 in the diagnosis and monitoring of pulmonary fibrosis (PF) in patients with systemic sclerosis (SSc), and to evaluate the differences between SP-D and KL-6. METHODS: Serum SP-D and KL-6 concentrations were determined by ELISA in 42 SSc patients. In a retrospective longitudinal study, 83 serum samples from 6 SSc patients were analyzed during a followup period of 0.6–6.3 years. RESULTS: SP-D and KL-6 concentrations at the first visit were higher in patients with SSc, especially those with PF, compared with healthy controls. Increased concentrations of SP-D were associated with decreased DLCO and decreased vital capacity in SSc patients more strongly than those of KL-6. The sensitivity and specificity for PF were 91% and 88% for SP-D and 39% and 100% for KL-6, respectively. In the longitudinal study, both SP-D and KL-6 concentrations were associated with activity of PF in patients with SSc. SP-D concentrations changed more rapidly than KL-6 concentrations, in parallel with the PF activity. CONCLUSION: SP-D was a more sensitive marker for PF than KL-6. By contrast, KL-6 showed higher specificity than SP-D. Combined use of these 2 serum markers would be more helpful to diagnose and monitor the PF activity in patients with SSc than single use of each marker.
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- 2004
16. Elevated Circulating CD40L Concentrations in Patients with Systemic Sclerosis
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Komura, Kazuhiro, Sato, Shinichi, Hasegawa, Minoru, Fujimoto, Manabu, and Takehara, Kazuhiko
- Abstract
OBJECTIVE: B cell activation, fibrosis, and expression of adhesion molecules on endothelial cells are regulated by soluble CD40L (sCD40L)/CD40 interactions. Since these effects are characteristic in patients with systemic sclerosis (SSc), serum concentrations of sCD40L were determined in patients with SSc. METHODS: Fifty-two Japanese patients with SSc were examined. They were grouped into 24 patients with limited cutaneous SSc (lSSc) and 28 with diffuse cutaneous SSc (dSSc). Serum sCD40L levels were examined by ELISA. As a disease control, serum samples from 20 patients with systemic lupus erythematosus (SLE) were also examined. In addition, a retrospective longitudinal study was performed in 71 serum samples from 18 patients with SSc. RESULTS: Serum sCD40L levels were elevated in SSc patients compared with healthy controls (p < 0.001). Levels of sCD40L in patients with SSc were higher than in patients with SLE (p < 0.001) that had elevated sCD40L levels compared with healthy controls. Among SSc subsets, there were no differences in sCD40L levels between lSSc and dSSc. sCD40L levels correlated positively with C-reactive protein levels in SSc patients (p < 0.0001, r = 0.449). In a cross-sectional study and a longitudinal study, serum sCD40L levels in dSSc patients were persistently elevated, although those in lSSc patients were temporarily elevated at the early phase of the disease process. CONCLUSION: Patients with SSc exhibited elevated sCD40L levels that may correlate with disease activity. These results suggest that CD40/CD40L interactions may be potential therapeutic targets in SSc.
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- 2004
17. Serum Concentrations of the CXC Chemokines Interleukin 8 and Growth-Regulated Oncogene-a Are Elevated in Patients with Systemic Sclerosis
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Furuse, Shinobu, Fujii, Hidetaka, Kaburagi, Yuko, Fujimoto, Manabu, Hasegawa, Minoru, Takehara, Kazuhiko, and Sato, Shinichi
- Abstract
OBJECTIVE: To determine whether serum concentrations of 2 CXC chemokines, interleukin 8 (IL-8) and growth-regulated oncogene-a (GRO-a), which are potent chemoattractants and activators for neutrophils, are elevated and whether they correlate with clinical features in patients with systemic sclerosis (SSc). METHODS: Serum samples from patients with diffuse cutaneous SSc (dSSc; n = 36), limited cutaneous SSc (lSSc; n = 42), systemic lupus erythematosus (SLE; n = 15), dermatomyositis (DM; n = 15), and healthy controls (n = 35) were examined by ELISA. RESULTS: Serum IL-8 was detected significantly more frequently in patients with dSSc (61%) and lSSc (55%) relative to healthy controls (6%), patients with SLE (7%), and those with DM (13%). Similarly, serum GRO-a concentrations in SSc patients were significantly increased compared with controls, patients with SLE, or those with DM. Elevated IL-8 concentrations significantly correlated with decreased % DLCO and rheumatoid factor positivity, while increased GRO-a levels were significantly associated with decreased % DLCO and % vital capacity, involvement of kidney and muscle, the presence of anti-topoisomerase I antibody, and increased serum IgG levels. CONCLUSION: Our results suggest that the elevation of serum levels of the CXC chemokines IL-8 and GRO-a is specific to SSc and that the elevation of CXC chemokines, particularly GRO-a, correlates with the involvement of internal organs, especially pulmonary damage.
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- 2003
18. Evaluation of Functional Disability Using the Health Assessment Questionnaire in Japanese Patients with Systemic Sclerosis
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Kuwana, Masataka, Sato, Shinichi, Kikuchi, Kanako, Kawaguchi, Yasushi, Fujisaku, Atsushi, Misaki, Yoshikata, Hatamochi, Atsushi, Kondo, Hirobumi, and Takehara, Kazuhiko
- Abstract
OBJECTIVE: To assess whether the functional disability in Japanese patients with systemic sclerosis (SSc) can be adequately evaluated by the Health Assessment Questionnaire (HAQ) developed in the United States. METHODS: The HAQ was completed by 121 Japanese patients with SSc, in whom SSc-specific physical examinations and laboratory tests were performed at the same time. Clinical findings associated with the disability index (DI) and individual components of the HAQ were examined using Student's t tests and Pearson's correlation tests. Logistic regression analysis was used to identify clinical findings that independently contributed to the increase in the HAQ-DI score. RESULTS: Japanese patients with SSc had significant functional disability, especially in the categories of eating and gripping, but the degree of disability was much less than was reported in previous studies carried out in the US. The increase in the HAQ-DI score was strongly correlated with increased total skin score, reduced oral aperture, reduced hand extension, increased finger flexion, subcutaneous calcinosis, flexion contractures, increased erythrocyte sedimentation rates, decreased percent vital capacity, and vascular involvement (p < 0.001 for all correlations). Multivariate logistic regression analysis showed that hand extension was the most important and an independent correlate of the HAQ-DI. CONCLUSION: Our multicenter, cross-sectional study has demonstrated that the self-administered HAQ is a valuable assessment tool of functional disability in Japanese SSc patients, who have social customs different from Americans, but functional disability measured by the HAQ is potentially influenced by ethnic variability.
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- 2003
19. Hypothesis: Pathogenesis of Systemic Sclerosis
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Takehara, Kazuhiko
- Published
- 2003
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