Biomedical subjects

H Ihn

Publications and source records attributed to H Ihn.

At least 91 records · Page 5Linked to original sources

PubMed1996

Clinical significance of serum levels of soluble interleukin-2 receptor in patients with localized scleroderma.

Localized scleroderma has been reported to be accompanied by abnormal immune reactions, including autoantibody production and lymphocyte activation. Lymphocyte activation can be quantitatively detected by measuring soluble interleukin-2 receptor (sIL-2R) in serum samples. In this study, serum sIL-2R levels were assayed by a sensitive enzyme-linked immunosorbent assay, in 48 patients with localized scleroderma, in 20 with systemic sclerosis (SSc) and in 20 healthy controls. Serum levels of sIL-2R were significantly higher in patients with localized scleroderma than in healthy controls. The serum levels of sIL-2R were correlated with the number of sclerotic lesions, the number of involved areas, the levels of anti-ssDNA, and the levels of antihistone antibody immunoglobulin M. Moreover, sIL-2R levels in sera from patients with SSc were also significantly higher than in healthy controls. Elevated serum levels of sIL-2R in localized scleroderma suggest that lymphocyte activation is one of the early processes in the development of this disease.

Adolescent↗

PubMed1995

Autoantibodies to pyruvate dehydrogenase complex in patients with systemic sclerosis. Possible role of anti-E1 alpha antibody as a serologic indicator for development of primary biliary cirrhosis.

OBJECTIVE: To determine the prevalence and clinical significance of anti-pyruvate dehydrogenase complex (anti-PDC) antibodies in systemic sclerosis (SSc). METHODS: Serum samples from patients with limited cutaneous SSc (n = 81) or diffuse cutaneous SSc (n = 63) were examined for anti-PDC antibodies by enzyme-linked immunosorbent assay (ELISA) and immunoblotting. RESULTS: IgG- and/or IgM-isotype anti-PDC antibodies were demonstrated by ELISA in 26 of 144 patients with SSc (18%). By immunoblotting, 19 patients had IgG anti-PDC antibodies. Among these patients with IgG anti-PDC antibodies, antibody to the E1 alpha subunit was significantly associated with the presence of laboratory abnormalities typical of primary biliary cirrhosis (PBC). CONCLUSION: Antibody to the E1 alpha subunit of PDC may be a serologic indicator for the development of PBC in patients with SSc.

Adult↗

PubMed1995

Autoantibodies to the heat-shock protein hsp73 in localized scleroderma.

We determined the presence of antibodies to the heat-shock protein hsp73 (anti-hsp73) in 57 serum samples from patients with localized scleroderma using an enzyme-linked immunosorbent assay (ELISA). In addition, 30 samples from healthy individuals, 30 from patients with systemic lupus erythematosus (SLE) and 32 from patients with systemic sclerosis were assessed. IgG and/or IgM anti-hsp73 antibodies were detected in 33% (19/57) of the patients with localized scleroderma. Among the three subtypes of localized scleroderma, generalized morphoea showed the highest incidence of anti-hsp73 antibodies (40%, 6/15). IgG and/or IgM anti-hsp73 antibodies were also detected in 9/30 samples (30%) from patients with SLE and in 13/32 samples (41%) from patients with systemic sclerosis, while the samples from the healthy controls were all negative for anti-hsp73. By immunoblotting, specific binding of antibodies to hsp73 was confirmed with representative serum samples that were positive for anti-hsp73 in the ELISA. Our findings indicate that the presence of anti-hsp73 is an additional immunological abnormality in localized scleroderma.

Adolescent↗

PubMed1995

Demonstration of interleukin-2, interleukin-4 and interleukin-6 in sera from patients with localized scleroderma.

Localized scleroderma has been reported to be accompanied by immunological abnormalities related to B cells, but little is known about T-cell activation in this disease. In this study, serum levels of interleukin-2 (IL-2), interleukin-4 (IL-4) and interleukin-6 (IL-6), which are known to be released by activated T cells, were determined using a sensitive enzyme-linked immunosorbent assay in 48 patients with localized scleroderma and 20 with systemic sclerosis, and in 20 healthy control subjects. IL-2, IL-4 and IL-6 were detected in serum from patients with localized scleroderma but not in that from healthy controls. The presence of antihistone antibodies correlated significantly with elevated IL-4 and IL-6 levels. Decreased serum levels of IL-2, IL-4 and IL-6 paralleled improvement in cutaneous sclerosis. Frequent detection of these lymphokines in serum from patients with localized scleroderma reflects T-cell activation in this disorder.

Autoantibodies↗

PubMed1995

Detection of antiribosomal P protein antibodies in patients with systemic sclerosis.

This study investigated the prevalence and clinical significance of anti-ribosomal P protein (anti-P) antibodies in patients with systemic sclerosis (SSc). Serum samples from 150 patients with SSc were examined by indirect immunofluorescence. ELISA and immunoblotting. Anti-P antibodies were detected in four (3%) patients with SSc. Three of the four patients showed SSc/SLE (systemic lupus erythematosus) overlap syndrome, but psychiatric disorders were not observed in these patients. By longitudinal immunoblotting analysis one patient, who was initially diagnosed with SSc, later developed anti-P antibodies along clinical manifestations of SLE. Our data suggest that anti-P antibodies are uncommon in SSc and that the presence of anti-P antibodies in patients with SSc indicates an overlap with SLE.

Adult↗

PubMed1995

Ultrasound measurement of skin thickness in systemic sclerosis.

Sclerotic skin change in systemic sclerosis (SSc) usually accompanies increased skin thickness. In order to quantify the cutaneous changes and to clarify the changes in the 'uninvolved' skin in systemic sclerosis (SSc), we measured the skin thickness on the chest, the forearms and the hands of 79 patients with SSc and 81 healthy controls with a B-mode ultrasound (30 MHz) apparatus. The thickness of the 'uninvolved', as well as the 'involved' skin in patients with SSc was significantly greater than that of healthy controls. Increased skin thickness on the forearms and/or the hands showed a 64.6% sensitivity and a 100% specificity for SSc. These results indicated that the skin which appears to be 'uninvolved' in patients with SSc is already pathologic, as shown by increased thickness. Moreover, measurement of skin thickness may be beneficial in the diagnosis of this disease at an early stage.

Adolescent↗

PubMed1995

Growth regulation in scleroderma fibroblasts: increased response to transforming growth factor-beta 1.

We investigated the responses of normal and scleroderma fibroblasts to various growth factors, especially transforming growth factor-beta 1 (TGF-beta 1). The effects of various growth factors on [3H]thymidine incorporation in normal and scleroderma fibroblasts were examined. [125I]-labeled platelet-derived growth factor (PDGF)-BB binding in scleroderma and normal fibroblasts was examined both in the presence and absence of TGF-beta 1 (1 ng/ml). Cytoplasmic protein was isolated and analyzed by Western blotting. Total RNA from fibroblasts was also isolated and analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) using specific primer sets. Mitogenic responses to TGF-beta 1 (0.33-1 ng/ml) in seven scleroderma fibroblast strains were significantly greater than those in normal controls. [125I]-PDGF-BB binding to scleroderma fibroblasts was increased after TGF-beta 1 stimulation. The increased response to TGF-beta 1 was shown to be mediated through PDGF-like protein induction; TGF-beta 1-treated scleroderma fibroblasts produced greater amounts of 36-kD PDGF-like protein, which was reported previously as connective tissue growth factor (CTGF), than did TGF-beta 1-treated normal fibroblasts. TGF-beta 1 treatment also upregulated PDGF-alpha receptor expression in scleroderma fibroblasts but not in normal dermal fibroblasts. mRNA expression of CTGF and PDGF-alpha receptor was correlated with the above protein expression. These observations suggest that the increased growth response to TGF-beta 1 in scleroderma fibroblasts is mediated through the induction of CTGF and PDGF-alpha receptor.

Cell Division↗

PubMed1995

Significant correlation between connective tissue growth factor gene expression and skin sclerosis in tissue sections from patients with systemic sclerosis.

The role of some growth factors and cytokines in the pathogenesis of systemic sclerosis (SSc) has been suggested. In particular, the contribution of transforming growth factor beta in the progression of skin sclerosis is suspected. Connective tissue growth factor (CTGF) was originally identified in human umbilical vein endothelial cells, and a recent study has revealed that human skin fibroblasts produce CTGF after stimulation with transforming growth factor beta. In the present study, the distribution of CTGF gene expression in tissue sections from patients with SSc was investigated by digoxigenin-labeled in situ hybridization. Strong CTGF mRNA signals were observed in the fibroblasts in sclerotic lesions, especially in the deep dermis, of the skin specimens from patients with SSc, whereas there was no expression in the skin from normal controls. The number of fibroblasts with positive hybridization signals was more abundant in the dermis from the sclerotic stage than in that from the inflammatory stage. Our findings indicate a correlation between CTGF gene expression and skin sclerosis and support the hypothesis that transforming growth factor-beta plays an important role in the pathogenesis of SSc, because transforming growth factor beta is the only inducer for CTGF identified to date.

Adolescent↗

PubMed1995

Elevated procollagen type I carboxyterminal propeptide production in cultured scleroderma fibroblasts.

BACKGROUND: We recently reported that the serum concentration of procollagen type I carboxyterminal propeptide (P1CP) in patients with systemic sclereosis (SSc) was elevated. In the present study, we investigated collagen metabolism in in vitro cultured scleroderma fibroblasts by measuring P1CP levels in the culture medium. METHODS AND RESULTS: Spontaneous P1CP production was 4.2 times higher in fibroblast cultures from patients with SSc (n = 11) than in those from healthy controls (n = 10). P1CP production in fibroblasts derived from diffuse cutaneous SSc patients was significantly greater than that from limited cutaneous SSc patients. The serum P1CP level in SSc patients was correlated with the P1CP production of cultured fibroblasts (r = 0.815, p < 0.005). Transforming growth factor beta increased P1CP production, and gamma-interferon decreased P1CP production similarly in both SSc and normal fibroblasts. In contrast, histamine dihydrochloride increased P1CP production only in SSc fibroblasts but not in controls. CONCLUSION: These findings suggest that P1CP production in SSc fibroblasts is relevant to in vivo collagen synthesis in SSc patients.

Adolescent↗

PubMed1995

The stimulatory effects of PDGF and TGF-beta 1 on dermal fibroblast attachment.

We investigated the effects of various growth factors (platelet-derived growth factor (PDGF), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), transforming growth factor-alpha (TGF-alpha), transforming growth factor-beta 1 (TGF-beta 1), tumor necrosis factor-alpha (TNF-alpha), keratinocyte growth factor (KGF)) on fibroblast attachment to plastic plates. It is thought that cell attachment to plastic plates in vitro may represent the step between cell migration and proliferation in vivo during wound healing. Among the growth factors examined, only PDGF and TGF-beta 1 significantly increased fibroblast attachment to both uncoated and collagen-coated plates in a concentration-dependent manner. The addition of anti-PDGF antibody abolished the enhancing effect of PDGF but not that of TGF-beta 1, suggesting that the effect of TGF-beta 1 is not through the autocrine induction of PDGF-related activities secreted by the fibroblasts themselves. These data suggest that PDGF and TGF-beta 1 regulate fibroblast attachment to the suitable environment in the process of dermal wound healing in vivo.

Adult↗

PubMed1995

Serum aldolase level is a useful indicator of disease activity in eosinophilic fasciitis.

The serum levels of muscle enzymes have been considered normal in patients with eosinophilic fasciitis (EF). We observed elevated serum aldolase levels in 3 patients with EF. Serum creatinine kinase levels were within the normal range. We measured the aldolase levels longitudinally. In all patients, the levels decreased to the normal range after oral corticosteroid treatment, and skin sclerosis improved. Afterwards, serum aldolase levels increased again, with the recurrence of skin sclerosis. These observations suggest that serum aldolase level may be a useful indicator of disease activity.

Adult↗

PubMed1994

Antihistone antibodies in systemic sclerosis. Association with pulmonary fibrosis.

OBJECTIVE: To determine the prevalence and clinical significance of antihistone antibodies (AHA) in systemic sclerosis (SSc). METHODS: Serum samples from patients with limited cutaneous SSc (n = 44), diffuse cutaneous SSc (dcSSc; n = 48), and other SSc-related disorders (n = 22) were examined by enzyme-linked immunosorbent assay and immunoblotting for AHA. RESULTS: AHA were demonstrated in 29% of the 92 SSc patients and in 44% of those with dcSSc. The presence of AHA correlated with severe pulmonary fibrosis in those with dcSSc. Immunoblotting revealed that the predominant antigen was histone H1. CONCLUSION: AHA might be a serologic indicator of the severity of pulmonary fibrosis in SSc.

Adult↗

PubMed1994

Serum concentration of procollagen type I carboxyterminal propeptide in systemic sclerosis.

The serum level of procollagen type I carboxyterminal propeptide (P1CP), which has been used as an index of collagen synthesis in patients with various fibrotic diseases during the active stage, was measured using enzyme-linked immunosorbent assay in 61 patients with systemic sclerosis (SSc) and in 21 control subjects. The mean P1CP level in the SSc patients was significantly higher than in the normal controls (mean +/- SD, 326 +/- 319 vs 128 +/- 87 ng/ml; p < 0.005). In 36% of the SSc patients, the serum P1CP level was significantly elevated more than two standard deviations above the mean control value. The mean serum P1CP level in patients with diffuse SSc was significantly higher than in those with limited SSc (411 +/- 373 vs 255 +/- 199 ng/ml; p < 0.05). In addition, the SSc patients with elevated serum P1CP levels showed a significantly greater incidence of lung fibrosis and joint involvement than those with normal P1CP levels (p < 0.005 and p < 0.05, respectively). These results suggest that the serum P1CP level is a useful indicator of the severity of disease in SSc patients.

Adolescent↗

PubMed1994

Clinical characteristics associated with antihistone antibodies in patients with localized scleroderma.

BACKGROUND: Recently we demonstrated the presence of antihistone antibodies (AHA) in localized scleroderma. OBJECTIVE: Our purpose was to determine clinical characteristics associated with AHA in patients with localized scleroderma. METHODS: We examined 57 serum samples by an enzyme-linked immunosorbent assay in the following three subgroups: 15 patients with generalized morphea, 27 with linear scleroderma, and 15 with morphea. We classified the patients as having generalized morphea when they had four or more lesions on at least two areas of the body, irrespective of whether the lesions were of morphea or linear type. RESULTS: AHA were detected in 42% of patients with localized scleroderma (24 of 57), and in 87% of patients with generalized morphea (13 of 15). The presence of AHA strongly correlated with the number of morphea lesions, the total number of lesions, and the number of involved areas of the body. However, AHA did not correlate with the presence or number of linear lesions. The presence of AHA showed a 87% sensitivity (13 of 15 patients) and a 74% specificity (31 of 42 patients) for generalized morphea. CONCLUSION: Our data suggest that AHA are a serologic marker for generalized morphea and that the validity of our new classification for generalized morphea is supported by the high frequency of AHA detection.

Adolescent↗

PubMed1994

Increased levels of circulating intercellular adhesion molecule-1 in patients with localized scleroderma.

BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) is important in immune-mediated mechanisms, and its circulating form (cICAM-1) may be an indicator of immune activation. Localized scleroderma is accompanied by various immunologic abnormalities. OBJECTIVE: We investigated whether the serum level of cICAM-1 in patients with localized scleroderma was elevated and was correlated with the clinical or serologic features of this disease. METHODS: Serum cICAM-1 levels were determined by an enzyme-linked immunosorbent assay in 48 patients with localized scleroderma, in 20 patients with systemic sclerosis, and in 20 healthy control subjects. RESULTS: Serum levels of cICAM-1 were significantly higher in patients with localized scleroderma than in the healthy control subjects. These levels correlated with the number of lesions, the number of involved areas, levels of antihistone antibody IgM, and levels of soluble interleukin 2 receptor. CONCLUSION: The results suggest that immune activation may be a factor in localized scleroderma.

Adult↗

PubMed1994

Antibodies to centromere and centriole in scleroderma spectrum disorders.

The importance of early detection of scleroderma spectrum disorders (SSD) has been emphasized. We determined the clinical distribution of anticentromere antibody (ACA) and anticentriole antibody in the following four groups: (1) 264 patients with SSD, including 193 with systemic sclerosis, 29 with mixed connective tissue disease and 42 with suspected secondary Raynaud's phenomenon (RP); (2) 26 patients with primary RP; (3) 248 patients with other connective tissue diseases, and (4) 139 patients with other skin diseases. The frequency of ACA was significantly higher in SSD (78/264, 30%) than in the other groups. In patients with SSD, the incidence of ACA in suspected secondary RP (28/42, 67%) was similar to that in type I systemic sclerosis (24/36, 67%). Anticentriole antibody was detected in only 1 patient with suspected secondary RP (0.4%) out of the 264 SSD patients. These data indicate that anticentriole antibody is very rare and that the antibodies against mitosis-related antigens such as centromere and centriole are associated with early SSD.

Adult↗

PubMed1994

Antigen specificity of antihistone antibodies in localized scleroderma.

BACKGROUND AND DESIGN: Recently, we detected antihistone antibodies (AHAs) in patients with localized scleroderma. However, the exact antigen specificity of AHAs in this disease is still unknown. Therefore, we determined the reactivity of AHAs with five individual histones and the correlation of AHAs with rheumatoid factor in localized scleroderma by means of enzyme-linked immunosorbent assay. Twenty patients with localized scleroderma who had IgG and/or IgM AHAs, as determined by enzyme-linked immunosorbent assay, were examined. These patients were classified into the following three subgroups: patients with generalized morphea (n = 11), patients with linear scleroderma (n = 6), and patients with morphea (n = 3). RESULTS: In generalized morphea, IgG AHAs strongly reacted with histones H1, H2A, and H2B; and IgM AHAs strongly reacted with H1 and H2B, as determined by means of enzyme-linked immunosorbent assay. The pattern of reactivity in linear scleroderma and morphea was similar to that in generalized morphea. A homogeneous immunofluorescent pattern on HEp-2 cells, which was produced by localized scleroderma sera, was completely abolished by absorption with total histones. By employing a latex agglutination test, IgM rheumatoid factor was detected in 60% of the 20 patients with localized scleroderma and at a frequency of 82% in those with generalized morphea. However, an absorption test of rheumatoid factor activity with human IgG revealed no cross-reactivity of AHAs with rheumatoid factor. CONCLUSIONS: Our data suggest that AHAs in localized scleroderma are directed against native chromatin, since H1, H2A, and H2B occupy a relatively exposed portion of chromatin.

Adolescent↗

PubMed1994

Serum concentration of procollagen type I carboxyterminal propeptide in localized scleroderma.

BACKGROUND AND DESIGN: Recently, we reported that the serum procollagen type I carboxyterminal propeptide (P1CP) level of patients with systemic sclerosis was elevated and correlated with disease severity. In this study, the serum level of P1CP was measured using the enzyme-linked immunosorbent assay in 39 patients with localized scleroderma and in 30 control subjects. RESULTS: The mean P1CP level in the patients was significantly higher than that in the normal control subjects. In 30% of the patients with localized scleroderma, the serum P1CP level was considered to be elevated (> 305 ng/mL; ie, 2 SDs above the mean control value). The mean serum P1CP level in the patients with generalized morphea was significantly higher than in the patients with morphea or linear scleroderma. In addition, the serum P1CP level in the patients with localized scleroderma was correlated with the number of sclerotic lesions, and it was negatively correlated with the duration of the disease. Anti-single-stranded DNA antibody and antihistone antibody were detected significantly more frequently in the patients with elevated P1CP than in the patients with normal P1CP. CONCLUSION: These findings suggest that the serum P1CP level is a useful indicator of disease severity in patients with localized scleroderma, as it has been found to be in those with systemic sclerosis.

Adolescent↗