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Biomedical subjects

H Ihn

Publications and source records attributed to H Ihn.

At least 19 recordsLinked to original sources
PubMed2006

The expression levels and the differential expression of transforming growth factor-beta receptors in dermatofibroma and dermatofibrosarcoma protuberans.

BACKGROUND: Dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP) are benign and intermediate malignant fibrotic dermal tumours, respectively. The contribution of transforming growth factor (TGF)-beta has been implicated in the progression of sclerosis in fibrotic diseases. OBJECTIVES: To investigate the expression of TGF-beta receptors in these fibrotic tumours. METHODS: We examined the expression levels of TGF-beta type I and type II receptors (TGFbeta-RI and TGFbeta-RII) in DF and DFSP using in situ hybridization and immunohistochemical analysis. We also examined the expression of TGF-beta1 and collagen type I using immunohistochemical analysis. RESULTS: We detected strong expression of TGFbeta-RI and TGFbeta-RII on epidermis and epidermal appendages, moderate expression in vascular endothelial cells, smooth muscle cells and neural tissues, and weak expression in fibroblasts in normal skin sections. The expression levels of TGFbeta-RI and TGFbeta-RII were elevated in the tissue sections of DF in comparison with normal dermal sections using in situ hybridization and immunohistochemical staining. Furthermore, the expression of TGFbeta-RI and TGFbeta-RII was strong in spindle-shaped cells around DF. The expression of TGFbeta-RI and TGFbeta-RII was decreased in DFSP in comparison with DF, and their expression was found to be homogeneous in each DFSP tumour cell. The staining for TGF-beta1 was found prominently on matrix and spindle-shaped tumour cells of DF, and peripheral regions of DFSP. Weak expression of TGF-beta1 was found on normal skin or tumour cells in the central part of DFSP. Type I collagen expression was found on spindle-shaped tumour cells in DF, but not in tumour cells of DFSP. CONCLUSIONS: These results suggest the possibility that TGF-beta signalling may contribute to the fibrosis around DF, and that TGF-beta receptors may play important roles in TGF-beta signalling. The expression patterns of TGFbeta-RI and TGFbeta-RII may be helpful in distinguishing these diseases.

Activin Receptors, Type I↗
PubMed2006

Heat shock protein 105 is overexpressed in squamous cell carcinoma and extramammary Paget disease but not in basal cell carcinoma.

BACKGROUND: Heat shock protein (HSP) 105 is a 105-kDa protein, recently discovered by serological analysis of recombinant cDNA expression libraries prepared from tumour cells (SEREX), and is still undergoing intensive research. SEREX can define strongly immunogenic tumour antigens that elicit both cellular and humoral immunity. Previous studies have shown that HSP105 is a cancer testis antigen and is overexpressed in various internal malignancies. The expression of HSP105 has not been studied in skin cancers. OBJECTIVES: To assess the expression of HSP105 in skin cancers including extramammary Paget disease (EMPD), cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). METHODS: Samples of EMPD (n = 25), SCC (n = 23, of which three were metastatic lesions) and BCC (n = 23) were collected from patients treated in our department between January 2002 and December 2004. Western blot and immunohistochemical staining methods were used to investigate the expression of HSP105. RESULTS: Results of Western blot analysis showed overexpression of HSP105 in EMPD and SCC, and minimal expression in BCC. Immunohistochemistry results showed that 56% of EMPD, 60% of primary and 100% of metastatic SCC highly expressed HSP105 while only 13% of BCC lesions showed increased staining. CONCLUSIONS: EMPD and SCC overexpress HSP105 while BCC does not. Tumours overexpressing HSP105 present ideal candidates for vaccination by HSP105-derived peptides or DNA.

Aged↗
PubMed2005

Constitutively phosphorylated Smad3 interacts with Sp1 and p300 in scleroderma fibroblasts.

OBJECTIVE: To elucidate the role of transforming growth factor-beta (TGF-beta)/Smad signalling in the increased expression of the collagen gene in systemic sclerosis (SSc) fibroblasts. METHODS: Dermal fibroblasts from seven patients with diffuse SSc of recent onset and from seven healthy individuals were studied. The expression levels of Smad2, Smad3 and Smad4 proteins were determined by immunoblotting. Smad3 phosphorylation and the interaction of Smad3 with Sp1 or p300 were analysed using immunoprecipitation. The effects of overexpression of Smad proteins or Sp1 on the human alpha2(I) collagen gene transcription were investigated with chloramphenicol acetyltransferase (CAT) assays using the -772 COL1A2/CAT construct. RESULTS: Constitutive increased Smad3 phosphorylation was detected in SSc fibroblasts compared with normal fibroblasts. Increased interaction of Smad3 with Sp1 as well as p300 was also detected in SSc fibroblasts. The overexpression of Smad3 caused an increase of up to 5-fold in COL1A2 promoter activity in normal fibroblasts, while Smad3 caused a small increase in COL1A2 promoter activity in SSc fibroblasts. However, neither Smad2 nor Smad4 caused significant effects in COL1A2 promoter activity in normal fibroblasts or SSc fibroblasts. The overexpression of Sp1 caused further increase in COL1A2 promoter activity stimulated by TGF-beta in normal fibroblasts, but did not change COL1A2 promoter activity in the presence of TGF-beta in SSc fibroblasts. The combined overexpression of Smad3 and Sp1 significantly enhanced TGF-beta response in normal fibroblasts, but less markedly in SSc fibroblasts. CONCLUSIONS: These results suggested that SSc fibroblasts are less sensitive to exogenous TGF-beta stimulation because they are already activated by the autocrine TGF-beta loop.

Cells, Cultured↗
PubMed2005

Clinical significance of serum levels of matrix metalloproteinase-13 in patients with systemic sclerosis.

OBJECTIVES: To investigate the clinical significance of serum matrix metalloproteinase-13 (MMP-13) levels in patients with systemic sclerosis (SSc). METHODS: Serum MMP-13 levels were determined by using a peptide substrate cleavage assay in 20 patients with diffuse cutaneous SSc (dcSSc), 20 with limited cutaneous SSc (lcSSc) and 10 normal controls. RESULTS: The serum MMP-13 levels in patients with dcSSc or lcSSc were significantly lower than those in normal controls (53.4 +/- 14.1 vs 73.2 +/- 11.5 ng/ml, P < 0.0005; 59.4 +/- 14.8 vs 73.2 +/- 11.5 ng/ml, P < 0.005, respectively), but there was no significant difference in the serum MMP-13 levels between patients with dcSSc and those with lcSSc. Disease duration prior to the diagnosis was significantly shorter in SSc patients with decreased serum MMP-13 levels than in those with normal levels (3.0 +/- 2.2 vs 8.6 +/- 7.6 yr, P < 0.0005). In addition, serum MMP-13 levels were moderately correlated with the duration of the disease (r = 0.451, P < 0.05). Though there was no significant difference in the frequencies of pulmonary fibrosis or reduced %DLco (diffusing capacity of lung for carbon monoxide), the frequency of reduced %VC (vital capacity) was significantly greater in patients with decreased serum MMP-13 levels than in those with normal levels (73 vs 24%, P < 0.05). CONCLUSIONS: Matrix metalloproteinase-13 may be involved in the fibrotic process of SSc, especially in the initiation of fibrosis. The serum MMP-13 levels may serve as a useful marker for the severity of pulmonary fibrosis in patients with SSc.

Adult↗
PubMed2005

Sclerosing panniculitis is associated with pulmonary hypertension in systemic sclerosis.

BACKGROUND: There have been no reports of patients with sclerosing panniculitis and systemic sclerosis (SSc). OBJECTIVES: To evaluate the incidence of sclerosing panniculitis in patients with SSc, and to investigate the clinical features of such cases. METHODS: In total, 128 patients with SSc treated at our clinic were investigated retrospectively. RESULTS: SSc patients with sclerosing panniculitis had pulmonary hypertension (PH), especially isolated PH, at a significantly higher incidence than those without. Among the SSc patients with PH, those with sclerosing panniculitis had pulmonary infarctions at a higher incidence than those without. CONCLUSIONS: Our results suggest that thrombosis caused by venous hypertension of the leg may be the main cause of PH in patients with SSc and sclerosing panniculitis. Sclerosing panniculitis may be a useful marker of PH in patients with SSc.

Adult↗
PubMed2005

Rheumatoid factor isotypes in localized scleroderma.

Localized scleroderma is a connective tissue disorder that is sometimes accompanied by various immunological abnormalities. In this study, we analysed serum levels of rheumatoid factor (RF) isotypes in patients with localized scleroderma and in normal controls to determine if any of these isotypes reflect the severity of the disease. IgM RF, IgG RF and IgA RF were positive in 30%, 21%, and 7% of the patients, respectively. The levels of IgM RF were significantly higher in the patients with generalized morphea (GM), the most severe form of localized scleroderma, than those with linear scleroderma (LS) (P < 0.005) or normal controls (P < 0.0005). The levels of IgG RF were significantly higher in patients with GM than normal controls (P < 0.05). The levels of IgA RF were significantly higher in patients with GM or LS than normal controls (P < 0.001 and P < 0.01, respectively). The count of sclerotic lesions was significantly higher in patients with IgM RF than those without (P < 0.05). These results suggest that the presence of RF isotypes is one of the immunological abnormalities of localized scleroderma. IgM RF seemed to be most useful of these three factors to determine the severity of disease.

Adolescent↗
PubMed2005

Drug-induced hypersensitivity syndrome associated with transient hypogammaglobulinaemia and increase in serum IgE level.

Drug-induced hypersensitivity syndrome (DIHS) is a rare but severe disease with multiorgan failure. Recently, the association of the human herpesvirus (HHV) family, particularly of HHV-6, with DIHS has been reported. We report a 43-year-old female diagnosed as having DIHS based on the clinical course and laboratory examinations. The HHV-6 reactivation was demonstrated by significantly increased levels of the specific antibody in her paired sera and by polymerase chain reaction of HHV-6 DNA. Notably, transient hypogammaglobulinaemia was detected in the early stage of the disease, which was associated with the disease activity. By contrast, the serum IgE level and eosinophils were increased 2 or 3 weeks later. In addition, serum levels of interferon gamma, interleukin (IL)-4 and soluble IL-2 receptor, which were increased in the early phase of the disease, decreased gradually after the corticosteroid therapy.

Adult↗
PubMed2004

Serum levels of tissue inhibitor of metalloproteinase-1 and 2 in patients with eosinophilic fasciitis.

BACKGROUND: Serum levels of tissue inhibitor of metalloproteinases (TIMPs) have been reported to be elevated in patients with various connective tissue diseases. However, there has been no report that evaluates TIMPs in patients with eosinophilic fasciitis (EF). OBJECTIVES: To determine serum TIMP-1 and TIMP-2 levels in patients with EF and to investigate their clinical significance. METHODS: Immunohistochemical stainings were performed in normal and EF skin samples. Serum TIMP-1 and TIMP-2 levels of 11 patients with EF and 12 healthy individuals were also measured with specific enzyme-linked immunosorbent assays. RESULTS: The fascia of EF patients was stained only by TIMP-1. Serum TIMP-1 levels (mean +/- SD) were significantly higher in EF patients than in healthy individuals (206.3 +/- 65.4 vs. 145.2 +/- 36.2 ng mL(-1), P < 0.01). Serum TIMP-1 levels in EF patients were significantly correlated with serum gamma-globulin and IgG levels (r = 0.86, P < 0.05; r = 0.83, P < 0.005, respectively). CONCLUSIONS: These results suggest that TIMP-1 is involved in the pathogenesis of EF, and that TIMP-1 may be a useful marker for the disease activity as well as serum gamma-globulin or IgG levels.

Adrenal Cortex Hormones↗
PubMed2004

Rheumatoid factor isotypes and anti-agalactosyl IgG antibodies in systemic sclerosis.

BACKGROUND: Rheumatoid factor isotypes and anti-agalactosyl IgG antibodies (anti-AG IgG) have been reported to be detected and correlated with the disease activity in some collagen diseases. OBJECTIVES: To study the frequency and the clinical significance of IgM, IgG and IgA rheumatoid factor (IgM-RF, IgG-RF and IgA-RF) and anti-AG IgG in patients with systemic sclerosis (SSc). METHODS: Seventy-nine serum samples from patients with SSc were examined by specific enzyme-linked immunosorbent assays. RESULTS: The levels of IgM-, IgG-, IgA-RF and anti-AG IgG were significantly higher in SSc patients than in normal healthy controls. The levels of IgM- and IgA-RF were significantly higher in patients with diffuse cutaneous SSc than in those with limited cutaneous SSc. IgM-, IgG- and IgA-RF and anti-AG IgG were significantly elevated in 39%, 32%, 23% and 35% of 79 SSc patients, respectively. The prevalence of pulmonary fibrosis, oesophageal involvement and cutaneous telangectasias in patients with elevated IgA-RF levels was significantly higher than in those with normal levels. The incidence of pitting scars of digits in those with elevated IgG-RF levels and the incidence of contracture of phalanges in those with elevated IgM-RF levels were significantly higher than in those with normal levels. The frequency of increased erythrocyte sedimentation rate in patients with elevated IgG-RF and the frequency of increased C-reactive protein in those with elevated IgM-RF were significantly greater than in those with normal levels. CONCLUSIONS: IgM-, IgG-, IgA-RF and anti-AG IgG can be serum indicators of specific clinical manifestations in SSc patients.

Adult↗
PubMed2004

Multiple dermatofibromas in a patient with systemic lupus erythematosus and Sjögren's syndrome.

Multiple dermatofibromas (DFs) are rare and have been thought to be associated with altered immunity. In this report, we describe a 27-year-old Japanese woman with systemic lupus erythematosus (SLE) and Sjögren's syndrome in whom eight nodules appeared over a period of 4 years. Histopathological findings were consistent with DF. SLE rather than Sjögren's syndrome seemed to have induced the multiple DFs in this patient. We also reviewed the reported cases with multiple DFs associated with SLE and/or Sjögren's syndrome. Review of the previous reports indicates that SLE is the most frequent autoimmune disorder associated with multiple DFs, and that both SLE and immunosuppressive treatments play a part in induction of multiple DFs. Therefore, if multiple DFs are present it is important that the status of the patient be evaluated from the standpoint of autoimmune diseases, particularly SLE, or immunosuppression.

Adult↗
PubMed2003

Elevated circulating soluble CD40 ligand in patients with mixed connective tissue disease.

Abnormalities of CD40 ligand have been demonstrated in various kinds of diseases. Our objective was to determine serum soluble CD40 ligand (sCD40L) levels in patients with mixed connective tissue disease (MCTD). Serum sCD40L levels of 23 patients with MCTD and 21 healthy individuals were measured with specific enzyme-linked immunosorbent assays. Serum levels of sCD40L were significantly higher in patients with MCTD than in healthy individuals (median 0.179 ng/ml vs 0.99 ng/ml, 25th-75th percentile; 0.117-0.296 ng/ml vs 0.82-1.70 ng/ml, P<0.005), whereas there were no significant correlation between elevated serum sCD40L levels and clinical or serological features in patients with MCTD. These results suggest that sCD40L plays a role in the pathogenesis of MCTD. Further studies are needed to clarify this.

Adult↗
PubMed2003

Plasma plasmin-alpha2-plasmin inhibitor complex levels are increased in systemic sclerosis patients with pulmonary hypertension.

OBJECTIVE: To determine the frequency and clinical significance of plasma plasmin-alpha(2)-plasmin inhibitor complex (PIC) in patients with systemic sclerosis (SSc). METHODS: Plasma samples from 74 patients with SSc and 32 healthy volunteers were examined by a specific enzyme-linked immunosorbent assay. RESULTS: Elevated plasma PIC levels were present in 35 of the 74 patients (47.3%) with SSc. The patients with elevated plasma PIC levels had pulmonary hypertension (PH) at a significantly higher incidence than those with normal PIC levels (31.4 vs 7.7%, P<0.01). When PH was classified into isolated PH (IPH) and secondary PH (SPH), the presence of IPH was significantly greater in patients with elevated PIC levels than in those with normal levels (25.7 vs 5.1%, P<0.02). CONCLUSIONS: These results suggest that plasma PIC levels may be a marker of PH, especially IPH, in patients with SSc.

Adult↗