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Biomedical subjects

M Jinnin

Publications and source records attributed to M Jinnin.

At least 19 recordsLinked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

A case of linear scleroderma with muscle calcification.

We report a 21-year-old man with linear scleroderma with muscle calcification revealed by a computed tomographic (CT) scan. Levels of serum calcium and phosphorus were normal. This is the first report of localized scleroderma with muscle calcification. Muscle involvement may cause contracture or functional abnormalities of the extremities. Therefore, CT scans may be useful in evaluating muscle involvement in patients with localized scleroderma.

Biopsy↗

Clinical significance of serum surfactant protein D (SP-D) in patients with polymyositis/dermatomyositis: correlation with interstitial lung disease.

OBJECTIVE: To determine the clinical significance of serum surfactant protein D (SP-D) levels in patients with polymyositis/dermatomyositis (PM/DM). METHODS: Serum SP-D levels were assayed using a sensitive enzyme-linked immunosorbent assay in 59 patients with PM/DM and in 29 healthy controls. RESULTS: The serum level of SP-D was significantly higher in patients with PM/DM than in healthy controls (mean+/-S.D. 61.7+/-122.6 vs 31.0+/-12.4 ng/ml, P < 0.01). The serum SP-D level in patients with interstitial lung disease (ILD) was significantly higher than in those without ILD (118.7+/-220.2 vs 38.7+/-21.0 ng/ml, P < 0.001). Serum level of SP-D was correlated with the presence of ILD. The incidences of decreased vital capacity (%VC) and of decreased diffusing capacity of carbon monoxidase (%DLCO) were also significantly greater in patients with an elevated SP-D level than in those with a normal level (64 vs 7%, P < 0.02; 73 vs 27%, P < 0.01). Moreover, the serum SP-D level was inversely correlated with %VC (r=-0.452, P < 0.01) and %DLCO (r=-0.349, P < 0.05). CONCLUSION: The serum SP-D level may be a useful marker for ILD in patients with PM/DM.

Adult↗

[An experimental study on the prevention of postlaminectomy scar formation: efficacy of interpositional collagen-sponge].

The efficacy of collagen-sponge to reduce postoperative scar formation was investigated in 65 Japanese white rabbits that received laminectomy in the 7th and 8th thoracic vertebra. The defect after laminectomy was filled by collagen-sponge in 25 rabbits, by free fat in 20 rabbits, and by nothing in 20 rabbits as controls. The animals were sacrificed 2, 4, 8 and 12 weeks and additional 5 rabbits of which defects were filled with collagen-sponge were sacrificed after 24 weeks. All the defects were examined histologically. At 4 weeks after laminectomy, the defects filled by collagen-sponge showed that fibrous tissue had invaded into the sponge, but there was no remarkable adhesion to the dura mater. At 8 weeks, the defect with collagen sponge showed foaming cells, and no thickening of the dura mater was observed. At 12 weeks, the grouping of foaming cells was partially replaced by fat cells. At 24 weeks, most of the foaming cells were replaced by fat cells, and the defect was then similar to that filled by free fat at 12 weeks. In contrast, the defect with no interposed membrane was already filled with fibrous tissue at 4 weeks, and adhesion to the dura mater was observed. Although the free-fat graft at 12 weeks postoperatively showed no remarkable adhesion around the dura mater, infiltration of fat tissue into the spinal canal was observed in 2 of 5 rabbits. These results indicated that collagen-sponge can be utilized as a new biomaterial to effectively prevent scar formation after laminectomy.

Animals↗