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Biomedical subjects

H Ihn

Publications and source records attributed to H Ihn.

At least 55 records · Page 3Linked to original sources
PubMed2000

Increased phosphorylation of transcription factor Sp1 in scleroderma fibroblasts: association with increased expression of the type I collagen gene.

OBJECTIVE: To determine the potential roles of transcription factors Sp1 and Sp3 in the increased expression of the human alpha2(I) collagen gene in scleroderma fibroblasts. METHODS: Dermal fibroblasts from 7 patients with diffuse systemic sclerosis (SSc; scleroderma) of recent onset and from 7 healthy individuals were studied. The levels of expression of alpha2(I) procollagen, Sp1, and Sp3 messenger RNA (mRNA), with or without stimulation by transforming growth factor beta (TGFbeta) or oncostatin M (OSM), were evaluated by Northern blot analysis, and the respective protein levels were determined by immunoblotting. The DNA binding activity of nuclear proteins recognizing the cis-acting elements in the human alpha2(I) collagen promoter was examined by gel mobility shift assays. The levels of Sp1 phosphorylation were investigated by immunoprecipitation using an antiphosphoserine-specific antibody. RESULTS: SSc fibroblasts showed basal alpha2(I) collagen mRNA levels that were approximately 3 times higher than those in normal fibroblasts. TGFbeta or OSM increased human alpha2(I) collagen mRNA expression in normal dermal fibroblasts, but these cytokines failed to increase alpha2(I) collagen mRNA levels in SSc fibroblasts. There were no significant differences in the levels of expression of Sp1 or Sp3 between SSc and normal fibroblasts. However, increased Sp1 phosphorylation was detected in SSc fibroblasts compared with normal fibroblasts. Mithramycin, a specific inhibitor of Sp1 binding, abolished the increased expression of the alpha2(I) collagen gene in SSc fibroblasts, in a dose-dependent manner. CONCLUSION: These results demonstrate the involvement of Sp1 in the up-regulation of expression of the alpha2(I) collagen gene in SSc fibroblasts.

Collagen↗
PubMed2000

Increased serum levels of soluble vascular cell adhesion molecule 1 and E-selectin in patients with localized scleroderma.

BACKGROUND: The serum levels of soluble forms of vascular cell adhesion molecule 1 (sVCAM-1) and E-selectin (sE-selectin) can be used as a marker of endothelial activation. OBJECTIVE: We investigated whether the serum level of sVCAM-1 and sE-selectin in patients with localized scleroderma (LSc) was correlated with the clinical or serologic features of this disease. METHODS: Serum samples from 59 patients with LSc, 20 patients with systemic sclerosis (SSc) and 29 healthy controls were examined using specific enzyme-linked immunosorbent assays. RESULTS: The serum levels of sVCAM-1 and sE-selectin in patients with LSc were significantly higher than those of the healthy controls. The serum levels of sVCAM-1 and sE-selectin were correlated with both the number of sclerotic lesions and the number of involved areas. CONCLUSION: These results indicate that the serum levels of sVCAM-1 and sE-selectin may reflect the extent of the skin involvement (ie, the disease severity) and may be useful for monitoring the in vivo states of endothelial activation in LSc.

Adult↗
PubMed2000

Serum levels of tissue inhibitor of metalloproteinases 2 in patients with systemic sclerosis.

BACKGROUND: The serum tissue inhibitor of metalloproteinases 1 (TIMP-1) level was reported to be a useful indicator of disease activity, especially of lung fibrosis in patients with systemic sclerosis. TIMP-2 is also an important inhibitor of matrix metalloproteinases (MMPs), such as interstitial collagenase, gelatinase, and stromelysin, which control the metabolism of the extracellular matrix. However, serum levels of TIMP-2 in patients with systemic sclerosis (SSc) have not been investigated. OBJECTIVE: We sought to determine the clinical significance of serum levels of TIMP-2 and MMP-2 in patients with SSc. METHODS: Serum samples were obtained from 128 patients with SSc (68 with limited cutaneous SSc and 60 with diffuse cutaneous SSc). Twenty-seven serum samples from healthy age- and sex-matched individuals were also examined as controls. The TIMP-2 and MMP-2 levels were determined by means of sandwich enzyme-linked immunosorbent assays. RESULTS: The serum TIMP-2 levels were elevated in 29 (22.7%) of the 128 patients with SSc and were significantly higher than those of the healthy control subjects. The serum TIMP-2 levels were significantly correlated with the extent of skin sclerosis in the patients with SSc. The incidence of decreased percentage of the diffusing capacity of lung for carbon monoxide (DLCO ) and that of an elevated erythrocyte sedimentation rate were significantly greater in the patients with elevated TIMP-2 levels compared with the patients with normal TIMP-2 levels (P <.05). When these patients were classified into 2 groups by disease activity, TIMP-2 levels were significantly more elevated in the high active group than in those low active group (P <.001). The serum MMP-2 levels of the patients with SSc were not significantly higher than those of the healthy control subjects. CONCLUSION: These findings suggest that the serum TIMP-2 level is a useful marker of the extent of skin sclerosis and disease activity in patients with SSc. The balance of TIMP-2 and MMP-2 may play an important role in patients with SSc. Furthermore, TIMP-2 may be thought to contribute to the development of disease in patients with SSc.

Adolescent↗
PubMed2000

Increased serum levels of soluble vascular cell adhesion molecule-1 and soluble E-selectin in patients with polymyositis/dermatomyositis.

BACKGROUND: Elevated levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble E-selectin (sE-selectin) have previously been reported in patients with various inflammatory diseases, but not in patients with polymyositis/dermatomyositis (PM/DM). OBJECTIVES: To determine serum levels and significance of sVCAM-1 and sE-selectin in patients with PM/DM. PATIENTS AND METHODS: Serum samples from 36 PM/DM patients, 30 patients with systemic sclerosis and 25 healthy control subjects were examined using specific enzyme-linked immunosorbent assay systems. RESULTS: The serum levels of sVCAM-1 in the PM/DM patients were significantly higher than those in the healthy controls. The elevated serum sVCAM-1 levels were correlated with the values of elevated erythrocyte sedimentation rate and elevated serum hyaluronate levels in the PM/DM patients. The serum sE-selectin levels in the PM/DM patients were also significantly higher than those in the healthy controls. The elevated serum sE-selectin levels were correlated with the incidence of elevated creatine kinase activities. The concentrations of serum sE-selectin were correlated with the serum tissue inhibitor of metalloproteinase-1 concentrations in the PM/DM patients (r = 0.53). CONCLUSIONS: These results suggest that serum sVCAM-1 and sE-selectin levels might be useful for detecting disease activity in patients with PM/DM.

Adolescent↗
PubMed2000

Characterization of autoantibodies to endothelial cells in systemic sclerosis (SSc): association with pulmonary fibrosis.

To determine the prevalence and the characterization of antibodies to endothelial cells in patients with SSc, serum samples from 80 patients with SSc, 20 patients with systemic lupus erythematosus (SLE), and 20 healthy control subjects were examined by ELISA using cultured human umbilical vein endothelial cells (HUVEC), indirect immunofluorescence analysis (IIF), and immunoblotting using cytoplasmic extract of HUVEC. IgG and/or IgM isotype anti-endothelial cell antibodies (AECA) were demonstrated by ELISA in 43 of 80 patients with SSc (54%), in 15 of 20 patients with SLE (75%), and in none of 20 healthy control subjects. Immunofluorescence analysis on HUVEC substrate showed homogeneous cytoplasmic staining. Immunoblotting demonstrated that these patients had antibodies directed to one or several antigens of approximately 60, 90, 110 and 140 kD, and the most common responses were to the 90-kD antigen. By the immunofluorescence method using HUVEC, affinity-purified anti-90-kD antibodies showed identical cytoplasmic staining to that produced by sera positive for AECA. Furthermore, AECA were closely correlated with pulmonary fibrosis in patients with SSc. These findings suggest that patients with SSc have abnormal antibodies to endothelial cell antigens, and support the hypothesis that endothelial dysfunction is involved in the development of this disease.

Adult↗
PubMed2000

Competition analysis of the human alpha2(I) collagen promoter using synthetic oligonucleotides.

Previous studies have identified four cis-response elements which mediate the basal transcriptional activity of the human alpha2(I) collagen gene. One of these elements, a pyrimidine-rich region (TCCCCC motif), was shown to be a repressor site, and the other three elements were shown to be activator sites. Furthermore, the repressor site and two of the activator sites were found to constitute binding sites for the transcription factors Sp1 and Sp3. In this study, we further determined the affinity and specificity of the binding of Sp1 and Sp3 to the human alpha2(I) collagen promoter and investigated the function of the pyrimidine-rich region which contains the TCCCCC motif. Functional analyses of Sp1 and Sp3 in Drosophila cells confirmed that Sp1 and Sp3 activate the human alpha2(I) collagen promoter via the GC boxes and the TCCTCC motif, but that binding of Sp1 or Sp3 to the repressor site does not activate or repress the collagen promoter activity. Com- petitive analyses using DNA mobility shift assays showed that the TCCCCC motif which constitutes the repressor site abolished the binding of Sp1 or Sp3 to the GC boxes or the TCCTCC motif, but not the binding of CCAAT-binding factor to the fourth cis-response element (CCAAT-binding factor site). Furthermore, the affinity of Sp1 or Sp3 for the TCCTCC motif was shown to be greater than that of the Sp1 consensus oligonucleotide. In vitro transcription analysis revealed that the addition of each activator site oligonucleotide or repressor site oligonucleotide had an inhibitory effect on the transcription of the collagen gene. These results suggest that the repressor site regulates the transcription of the collagen gene by taking away Sp1 or Sp3 from the activator sites.

Binding Sites↗
PubMed2000

Clinical and laboratory features of scleroderma patients with pulmonary hypertension.

OBJECTIVE: Pulmonary hypertension (PH) is a frequent cause of death in patients with systemic sclerosis (SSc). In this study, we examined the occurrence of PH and investigated the clinical and laboratory features of SSc patients with PH. METHODS: A cross-sectional study of 125 Japanese patients with SSc was conducted using Doppler echocardiography, other multiple cardiopulmonary tests, and laboratory examination. RESULTS: PH (systolic pressure >40 mmHg) was diagnosed in 20 patients (16%) by Doppler echocardiography. In the six patients who had secondary pulmonary hypertension (SPH), PH was due to severe pulmonary fibrosis; 14 patients had isolated pulmonary hypertension (IPH). An elevated erythrocyte sedimentation rate (ESR) and increased immunoglobulin G (IgG) were found in a significantly greater proportion of the patients with PH than in those without PH. The incidence of pitting scars/ulcers was significantly greater in the patients with SPH than in those without PH. CONCLUSION: Elevated ESR and increased IgG were common features of scleroderma patients with PH, and scleroderma patients with SPH were inclined to have pitting scars/ulcers.

Adult↗
PubMed2000

Serum KL-6 in adult patients with polymyositis and dermatomyositis.

OBJECTIVE: To determine the serum levels of KL-6, a mucin-like high-molecular-weight glycoprotein, in polymyositis/dermatomyositis (PM/DM) patients. METHODS: Serum samples from 42 adult PM/DM patients and 38 healthy control subjects were examined using specific enzyme-linked immunosorbent assay (ELISA) systems. RESULTS: The serum levels of KL-6 in the PM/DM patients were significantly higher than those of the healthy controls. The elevated serum KL-6 levels correlated with the presence of interstitial lung disease (ILD) and decreased percentage diffusing capacity of carbon monoxide (%DLco) in the PM/DM patients. The serum KL-6 levels inversely correlated with %DLco and percentage vital capacity. Additionally, the serum KL-6 levels were elevated in five of the seven DM patients with malignant neoplasia. CONCLUSIONS: These results suggest that the serum KL-6 level might be a useful serum marker for ILD and internal malignancy in PM/DM.

Adult↗
PubMed2000

[A case of very late onset overlap syndrome of systemic sclerosis and systemic lupus erythematosus].

A 88-year-old woman was admitted with appetite loss and dehydration in April 1999. She first noticed finger swelling in May 1996 and systemic sclerosis (SSc) was diagnosed in February 1997 on the basis of a clinical picture of low-grade fever, diffuse skin thickening, Raynaud's phenomenon, and pulmonary fibrosis. Retrospectively pulmonary fibrosis could have been identified on chest X ray film in September 1995. Although her appetite loss and dehydration were improved by hydration, pleural effusion continued. After detailed examinations, anti-topoisomerase 1 (Scl-70) antibody, anti-Sm antibody, and an anti-double-stranded DNA antibody (dsDNA) were found in her serum. However, the other antibodies to anti-SS-A, SS-B, Jo-1, and RNP were not detected. These results suggest that this elderly case was a very late onset overlap syndrome of systemic lupus erythematosus (SLE) and SSc. Thus, the pleural effusion in this case may have been caused by SLE-associated pleuritis. Although the late onset elderly cases with overlap syndrome are very rare, SLE, SSc, and their combination can be found in aged patients over 80 years old. SLE and SSc should be carefully considered for the differential diagnosis of pleural effusion and skin thickening even in elderly patients.

Aged↗
PubMed2000

Circulating levels of soluble CD30 are increased in patients with localized scleroderma and correlated with serological and clinical features of the disease.

OBJECTIVE: To determine serum soluble CD30 (sCD30) levels in patients with localized scleroderma. METHODS: Serum soluble CD30 levels were assayed by a sensitive ELISA in 55 patients with localized scleroderma, in 15 with systemic sclerosis (SSc), and in 20 healthy controls. RESULTS: Serum levels of sCD30 were significantly higher in patients with localized scleroderma than in healthy controls. Serum levels of sCD30 were correlated with the number of sclerotic lesions, the number of involved areas, levels of anti-histone antibody IgM, and levels of interleukin 6. sCD30 levels in sera from patients with SSc were also significantly higher than in healthy controls. CONCLUSION: These results suggest possible involvement of Th2 cells in the immunopathogenesis in localized scleroderma, and serum sCD30 levels may be helpful in following the outcome of the disease.

Adolescent↗
PubMed2000

Serum levels of KL-6 as a useful marker for evaluating pulmonary fibrosis in patients with systemic sclerosis.

OBJECTIVE: KL-6 is a mucin-like glycoprotein that is strongly expressed on type II pneumocytes in the lung. Circulating KL-6 has been shown to be a sensitive marker of the disease activity of interstitial lung diseases. We determined the serum levels of KL-6 in patients with systemic sclerosis (SSc) and investigated whether these levels would serve as a useful marker of pulmonary fibrosis (PF) in patients with SSc. METHODS: The serum KL-6 levels were determined using a specific ELISA in 91 patients with SSc, and in 38 healthy controls. RESULTS: The serum levels of KL-6 were significantly higher in patients with SSc than in healthy controls (923+/-860 vs. 382+/-55 U/ml; p<0.0001). The serum KL-6 levels of the patients with diffuse cutaneous SSc (dSSc) tended to be higher than those with limited cutaneous SSc (ISSc) (1054+/-1000 vs. 800+/-694 U/ml), but there was no significant difference between these 2 groups. The serum KL-6 levels in the patients with PF were significantly elevated compared to those without PF (1283+/-1056 vs. 520+/-148 U/ml; p<0.0001). Moreover, DLCO and VC were also significantly decreased in the patients with elevated KL-6 levels compared to those with normal levels (62+/-22% vs. 72+/-17%, p<0.05; 87 +/-20% vs. 100+/-18%, p<0.01, respectively). CONCLUSION: Serum KL-6 level may be a useful serum marker for evaluating pulmonary fibrosis in patients with SSc.

Adult↗
PubMed2000

Serum levels of soluble interleukin 6 receptor and soluble gp130 are elevated in patients with localized scleroderma.

OBJECTIVE: To investigate the clinical relevance of serum soluble interleukin 6 receptor (sIL-6R) and soluble gp130 (sgp130) in localized scleroderma. METHODS: Serum levels of sIL-6R and sgp130 were examined by ELISA in 45 patients with localized scleroderma. Twenty patients with systemic sclerosis (SSc) and 20 healthy individuals served as controls. RESULTS: Serum levels of both sIL-6R and sgp130 were significantly elevated in patients with localized scleroderma compared with healthy controls. Moreover, serum sgp130 levels in patients with localized scleroderma were significantly higher than in patients with SSc. In patients with localized scleroderma, elevated sIL-6R levels significantly correlated with levels of IgM antihistone antibodies, the presence of rheumatoid factor, the number of linear lesions, and the number of body areas involved. Elevated sgp130 levels were significantly associated with levels of IgG antihistone antibodies, the number of plaque lesions, the total number of lesions, and the number of body areas involved. CONCLUSION: These results suggest that elevated serum sIL-6R and sgp 30 may reflect activation of the IL-6 system that may be associated with the development of sclerotic lesions and autoantibody production in localized scleroderma.

Adolescent↗
PubMed2000

[Scleroderma].

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Antibodies, Antinuclear↗
PubMed1999

Dermatomyositis with elevated serum hyaluronate.

We report two Japanese patients with dermatomyositis whose serum hyaluronate levels were correlated with their disease activities. The diagnosis of one patient was primary idiopathic dermatomyositis, and that of the second patient was dermatomyositis associated with neoplasia. The serum hyaluronate level of the former patient was decreased by systemic corticosteroid therapy, and that of the latter patient decreased following the surgical resection of mammary carcinoma and subsequent chemotherapy. The disease activity of each patient was greatly improved after these therapies. The longitudinal measurement of serum hyaluronate concentration may be useful to estimate the disease activity of patients with dermatomyositis whose initial serum levels of hyaluronate are elevated.

Adult↗
PubMed1999

Distribution and antigen specificity of anti-U1RNP antibodies in patients with systemic sclerosis.

Systemic sclerosis (SSc) is a generalized connective tissue disease which is characterized by the presence of several autoantibodies. To determine the prevalence and antigen specificity of anti-U1RNP antibodies (anti-U1RNP) in patients with SSc, serum samples from 223 patients with SSc, 117 patients with systemic lupus erythematosus (SLE), 18 patients with mixed connective tissue disease (MCTD) and 40 healthy control subjects were examined by indirect immunofluorescent analysis (IIF), double immunodiffusion, and immunoblotting using nuclear extract of HeLa cells. Eighteen of the 223 (8%) serum samples from patients with SSc were shown to be positive for anti-U1RNP. The frequency of anti-U1RNP positivity in limited cutaneous SSc (14%) was significantly higher than that in those with diffuse cutaneous SSc (3%). Anti-Sm antibodies were detected in patients with SLE positive for anti-U1RNP, but not in those with SSc positive for anti-U1RNP or those with MCTD. Immunoblotting demonstrated that anti-70-kD antibodies were detected more often in patients with SSc positive for anti-U1RNP and in those with MCTD than in those with SLE. Furthermore, anti-U1RNP was closely correlated with pulmonary fibrosis and joint involvement in patients with SSc. These results suggest that anti-70-kD antibodies are useful in the classification of patients with anti-U1RNP.

Antibodies, Antinuclear↗
PubMed1999

Prevalence and antigen specificity of anti-histone antibodies in patients with polymyositis/dermatomyositis.

Anti-histone antibodies have been detected in the sera of patients with various autoimmune diseases. The existence of anti-histone antibodies in patients with polymyositis/dermatomyositis, however, has not been reported. We found anti-histone antibodies in eight (17%) of 46 sera from patients with polymyositis/dermatomyositis by an enzyme-linked immunosorbent assay. One serum was positive for both IgG anti-histone antibodies and IgM anti-histone antibodies. Six sera were positive only for IgG anti-histone antibodies. One serum was positive only for IgM anti-histone antibodies. An indirect immunofluorescence analysis using HEp-2 cells as the substrate showed that all sera positive for anti-histone antibodies produced homogeneous nuclear fluorescence. This immunofluorescence pattern disappeared after absorption of anti-histone activity with total histones. An immunoblotting analysis demonstrated that the anti-histone antibodies were predominantly directed against histone H1 in all seven sera with IgG anti-histone antibodies. Weak reactivity with H2B and H4 were also found in three sera from the patients with polymyositis/dermatomyositis. Sera from two patients with polymyositis/dermatomyositis displayed anti-H2A and H3 activity. One of the two sera showed IgM anti-histone antibodies in the enzyme-linked immunosorbent assay reacted with H1, H2A, H2B, H3, and H4, whereas the other serum reacted with no fractions of total histones. The activity of anti-histone antibodies disappeared in immunoblotting after absorption with total histones. All of the patients with anti-histone antibodies were free from lung fibrosis or internal malignancies. Thus, our data indicate that the presence of anti-histone antibodies is classified as one of the serologic abnormalities observed in polymyositis/dermatomyositis.

Adolescent↗
PubMed1999

Enhanced production of interleukin-6 (IL-6), oncostatin M and soluble IL-6 receptor by cultured peripheral blood mononuclear cells from patients with systemic sclerosis.

OBJECTIVES: To determine whether the spontaneous production of interleukin 6 (IL-6), oncostatin M (OSM), soluble IL-6 receptor (sIL-6R) and soluble gp130 (sgp130) from peripheral blood mononuclear cells (PBMC) is increased in patients with systemic sclerosis (SSc). METHODS: The culture supernatants of PBMC from patients with SSc (n = 33) and healthy controls (n = 20) were examined by enzyme-linked immunosorbent assay. RESULTS: The production levels of IL-6, OSM and sIL-6R were significantly higher in patients with SSc than in controls. However, sgp130 levels in supernatants from patients with SSc were not significantly elevated when compared with those from controls. Soluble IL-6R levels correlated significantly with the severity of pulmonary fibrosis in patients with SSc. CONCLUSIONS: The enhanced production of IL-6, OSM and sIL-6R from PBMC may cooperatively contribute to the disease process in SSc. In particular, enhanced sIL-6R production from PBMC may be related to the development of pulmonary fibrosis via enhancement of IL-6 signal transduction in SSc, since sIL-6R can act as an agonist of IL-6.

Adolescent↗