Kazuhiko Takehara

..Based on these data, we hypothesize that a 2-step process of fibrosis occurs in SSc: that is, TGF-beta induces fibrosis in the early stage and afterwards CTGF acts to maintain tissue fibrosis...

..Here we summarize previous data on the autoimmunity of localized scleroderma, mostly published in the last two decades, because there has not been a review paper summarizing autoimmunity in this disorder...

..In the 21st century, we speculate that cocktails of various growth factors may permit subtle growth regulation of skin fibroblasts; such technology would have applications in the treatment of many skin diseases...

..8+/-7.0 after one year of treatment (p < 0.005) and to 8.7+/-6.1 at final evaluation (p < 0.001). Thus, we confirmed the usefulness of oral corticosteroid treatment for early dSSc in Japanese patients...

..Thus, our findings indicate that ICAM-1 expression contributes to the development of skin fibrosis in TSK/+ mice, especially via ICAM-1 expressed on skin fibroblasts...

..These results indicate that skin wound healing is regulated cooperatively by all selectins and ICAM-1 and may provide critical information for the therapy of skin wounds...

..The IgE-mediated cutaneous reverse passive Arthus reaction may serve as an experimental model for cutaneous eosinophilic infiltration in vasculitis as well as in other diseases...

..These results suggest that E- and P-selectins synergistically inhibit lung fibrosis by promoting the recruitment of NKT cells...

..These results indicate that UV exposure inhibits CHS by abrogating up-regulation of endothelial ICAM-1 expression after Ag challenge at elicitation sites...

..Thereby, B-cell depletion during disease onset suppressed skin fibrosis, indicating that B cells contribute to the initiation of systemic sclerosis pathogenesis in tight-skin mice but are not required for disease maintenance...

..The infiltrated mast cells and macrophages may also contribute to the maintenance of fibrosis...

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..These results suggest that bFGF induces collagen production by stimulating skin fibroblasts and CTGF cooperates with bFGF. Our results indicate that the induction of MCP-1 is necessary for infiltration of inflammatory cells...

..Thus, VCAM-1 plays a complementary role to ICAM-1 in the cutaneous Arthus reaction by regulating leukocyte accumulation and proinflammatory cytokine production...

..Collectively, P- and E-selectins cooperatively regulate CH response, although their roles may be different depending on the phase of the reaction...

..The results suggest that BAFF/BAFF receptor system is critical for the development of skin fibrosis in TSK/+ mice and could be a potent therapeutical target...

..CONCLUSION: Elevated serum PARC levels correlated with PF and more sensitively reflected the PF activity than did serum KL-6 or SP-D levels in SSc. Serum PARC levels may be a useful new serum marker for active PF in SSc...

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..These results suggest that both a Th1 chemoattractant MIG and Th2 chemoattractants, TARC and MDC, cooperatively play a role in the development of ABD...

..Thus, CD19 modulates the Th1/Th2 cytokine balance in B cells and plays a critical role as a suppressive molecule in the development of EAE...

..The antigenic stimulus in SLE may be different from other connective tissue diseases and is more likely to be native chromatin...

..Although the ICOS/ICOSL pathway is known to play various roles in adaptive immunity, its roles in innate immunity and tissue fibrosis remain unknown...

..To determine serum concentrations of pentraxin 3 (PTX3) and its clinical associations in patients with systemic sclerosis (SSc)...

..This suggests that these adhesion molecules are potential therapeutic targets for inhibiting human pulmonary fibrosis...

..These results indicate that L-selectin and ICAM-1 contribute cooperatively to the development of Con A-induced hepatitis by regulating leukocyte infiltration and subsequent cytokine production...

..To determine serum levels of soluble CD40 (sCD40) and clinical association in patients with systemic sclerosis (SSc)...

..Although abnormalities of various chemokines are detected in systemic sclerosis (SSc), there are few findings concerning Th1 or Th2 chemoattractants...

..These results suggest that a decrease in CD22 expression may not be associated with BP-specific antibody production...

..These results suggest that elevated anti-MSRA autoantibody is associated with the disease severity of SSc and may enhance the oxidative stress by inhibiting MSRA enzymatic activity...

..Our objective was to assess the changes and red blood cell velocity in finger nail-fold capillaries using nail-fold video capillaroscopy (NVC) in patients with adult-onset DM...

..To determine serum concentrations of soluble CXCL16 and its clinical associations in patients with systemic sclerosis (SSc)...

..These results suggest that elevated serum levels of APRIL are associated with disease severity and activity in AD, and APRIL may have an important role in the pathogenesis of AD...

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..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)...

..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...

..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...

..Thus, our results indicate that ICOS-ICOSL costimulatory signaling has critical roles during wound healing, most likely by inducing IL-6 production...

..Our purpose was to determine the serum levels and frequency of antiphospholipid antibodies (aPLs) and confirm the clinical importance of these antibodies in patients with autoimmune blistering disease (ABD)...

..To determine serum levels of tumor necrosis factor-related weak inducer of apoptosis (TWEAK) and its clinical associations in patients with systemic sclerosis (SSc)...

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..We propose that this is a useful model for investigating the mechanism of pressure ulcer formation using various transgenic mice...

..These results suggested that altered NK cell function contributes to immunological abnormalities in SSc...

..The results of the present study indicate that anti-topo II alpha Ab represent one of the autoantibody specificities detected on SSc patients and may be regarded a serological marker of pulmonary fibrosis in Japanese patients with SSc...

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..These results suggest that monitoring both sICAM-1 and sL-selectin is available to evaluate the progression of MM...

..To clarify the association of clinical and prognostic features with dermatomyositis (DM)-specific autoantibodies (Abs) in adult Japanese patients with DM...

..Fractalkine (FKN) induces activation and adhesion of leukocytes expressing its receptor, CX(3)CR1. FKN is released from the cell surface through proteolytic cleavage as soluble FKN (sFKN)...

..Thus, altered B cell function may result in tissue fibrosis, as well as autoimmunity, in SSc...

..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...

..By contrast, serum BAFF levels were not significantly elevated in patients with pemphigus or pemphigoid. These results suggest that BAFF may be contributing to autoimmunity and disease development in localized scleroderma...

..The enhanced production of some cytokines may be related to the pathogenesis of localized scleroderma (LSc)...

..CONCLUSION: Our results suggest that anti-LPL autoantibody contributes to elevated serum triglyceride levels by inhibiting LPL enzyme activity in patients with SSc...

..CD23, a low affinity Fc receptor for IgE, is mainly expressed on mature B lymphocytes. Studies have suggested that serum levels of soluble CD23 (sCD23) correlate with serum IgE levels and disease severity in BP...

..CONCLUSION: These results suggest that BAFF and its signaling in B cells contribute to B cell abnormalities and disease development in patients with SSc...

..These results indicate that CCR1, CCR5, and CCL3 cooperatively contribute to the cutaneous Arthus reaction, and also suggest that enhanced expression of CCL3 and CCL5 compensates for the loss of CCR1, CCR5, and CCL3 in the reaction...

..Recently, sentinel lymph nodes outside traditional nodal basins have been identified. This study investigated the incidence of sentinel nodes in the popliteal region and the indication for biopsy...

..CONCLUSION: Rapidly increased serum KL-6 levels during disease course were associated with new onset or deterioration of PF...

..CD19 deficiency also inhibited IL-6 production by TSK/+ B cells. Thus, chronic B cell activation resulting from augmented CD19 signaling in TSK/+ mice leads to skin sclerosis possibly through IL-6 overproduction as well as autoimmunity...

..The purpose of this study was to determine the prevalence of anti-CCP antibodies (anti-CCP Abs) and to assess associations between the presence of anti-CCP Ab and arthritis or arthralgia in SSc patients...

..Coexpression of various KLK and SPINK5 mRNA suggests that their proteins are the candidates to balance and maintain serine protease activities in both the skin and appendages...

..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...

..This case suggests a role for anti-topo I in the pathogenesis of systemic sclerosis and an effect of corticosteroids on skin sclerosis and autoantibody production...

..Previous studies suggest that CCL13 may have some role in the pathogenesis of systemic sclerosis (SSc)...

..These results suggest that anti-MMP-3 antibody is a serological marker that reflects the severity of SSc and also suggest that it may contribute to the development of fibrosis by inhibiting MMP-3 activity and reducing the ECM turnover...

..Tc1 cells may be associated with pulmonary vascular damage in SSc...

..Therefore, it has been hypothesized that antihistone antibody is induced by nucleosome or native chromatin as immunogens in LSc...

..CONCLUSIONS: The increased serum CTACK levels and enhanced skin CTACK expression in SSc patients suggest that CTACK is related to the inflammation associated with SSc...

..The role of endoglin in SSc is potentially intriguing since limited cutaneous SSc (lcSSc) and HHT share several symptoms, including telangiectasia...

..Calpain II expression was up-regulated in psoriasis skin lesions compared with normal skin while calpastatin expression was normal. The results of this study reveal the presence of anti-calpastatin autoantibody in psoriasis...

..In this study, we identified a novel MSA reactive with 155 and 140 kDa nuclear proteins [anti-155/140 antibody (Ab)] and determined the clinical feature of DM patients positive for this autoantibody (autoAb)...

..The animal model on skin fibrosis by exogenous application of growth factors developed in this study may prove useful for future studies on fibrotic disorders...

..CONCLUSIONS: These results suggest the potential clinical significance of anti-topo I antibody levels in evaluating disease severity and the prognosis in SSc...

..The results indicate that L-selectin and ICAM-1 contribute co-operatively to the anti-tumour reaction by regulating lymphocyte infiltration to the tumour...

..CONCLUSION: Elevated sCD44 levels were associated with a relatively mild subset of SSc. These results suggest that CD44 could be a potential therapeutic target in SSc...

..However, a longer-term prospective study in a larger population will be needed to confirm its clinical utility as predictors of outcomes...

..Reactivation of HHV family members is generally characterized by increased serum antibody titers against the virus. By contrast, clinical symptoms caused by viral reactivation are relatively rare...

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..The relationship between gastroesophageal reflux (GER) symptoms and dysmotility was examined in endoscopically confirmed patients suspected of having reflux esophagitis...

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..Our findings suggest an increase in Tc2 cell number in blood from psoriatic patients, and the association of Tc2 cells with inflammation in psoriasis...

..Although a severe type 1 reaction developed after four months of treatment, he was treated with oral prednisolone at a dose of 40 mg/day...

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..Thus, the enhanced production of TGF-beta by PBMC may contribute to the disease process in SSc..

..Despite the poor prognosis for patients with lymph node metastasis, management of extramammary Paget's disease without clinical evidence of involved nodes is controversial...

..Thus, chronic B cell activation resulting from augmented CD19 signaling leads to skin fibrosis possibly through IL-6 overproduction, as well as autoantibody production, in tight-skin mice and SSc patients...

..Oesophageal complications are common in systemic sclerosis (SSc). However, the ability to determine the severity of oesophageal complications according to SSc type and skin lesion has not been evaluated...

..05), 7 days (P<0.05) and 14 days (P<0.05) after starting the treatment with lipo-PGE1. These results suggest that L-selectin may be involved in the disease process in SSc, and lipo-PGE1 may alter some inflammatory events in SSc...

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..Thus, serum levels of IL-6 and IL-10 most strongly reflect the extent of skin thickening in SSc, suggesting that levels of IL-6 and IL-10 are useful serological indicators for skin fibrosis in SSc...

..To evaluate immunohistochemistry and reverse transcriptase polymerase chain reaction (RT-PCR) for melanoma associated antigens (MAA) in detecting occult melanoma cells in lymph nodes which were missed on routine pathology...

..In addition, serum IgG levels were correlated with serum interleukin-6. Thus, serum IgG levels are associated with PF in patients with SSc and anti-topoisomerase I antibodies and in patients with SSc and ACA...

..To assess the association of CD40/CD40 ligand (CD40L) interactions with the development of skin fibrosis and autoimmunity in tight-skin (TSK/+) mouse, which is a mouse model for human systemic sclerosis...

..Immunologic analysis revealed that production of anti-desmoglein 1 autoantibodies started when SCC metastasized, and the SCC expressed desmoglein 1, suggesting a pathogenic role of metastasized SCC in developing pemphigus foliaceus...

..To determine serum levels of soluble CD31 (sCD31) and its clinical associations in patients with systemic sclerosis (SSc)...

..This unique regulation may contribute to the autoimmune aspect of SSc...

..This finding is unusual, and it suggests that the target antigen, which is involved in acantholysis, may be other than Dsg 3 in this case...

..To determine serum levels and spontaneous production by peripheral blood mononuclear cells (PBMC) of interleukin 12 (IL-12), a potent inducer of type 1 helper (Th1) T cells, in patients with systemic sclerosis (SSc)...

..This report demonstrates a link between this autoimmune subepithelial blistering disease and malignancy. It is of interest and potential great importance to examine other cases of AeCP for such a potential association...