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Biomedical subjects

N Yazawa

Publications and source records attributed to N Yazawa.

At least 37 records · Page 2Linked to original sources

Prevalence in myositis of antibodies recognizing anti-U3 RNA probably in a novel complex with 22/25 kD protein and not fibrillarin.

New antibodies against a U3 snRNP, which were named anti-Myo 22/25 antibodies, were detected in four (8%) of 53 serum samples from patients with polymyositis/dermatomyositis (PM/DM) by RNA immunoprecipitation. In the protein immunoprecipitation analysis, all four serum samples precipitated 22 kDa and 25 kDa proteins, which were not precipitated by normal serum or serum positive for antifibrillarin antibodies. Three of the four PM/DM patients had other identified autoantibodies including anti-PL-12 antibodies, antihistone antibodies (AHA), anti-SS-A antibodies and anti-SS-B antibodies defined by double immunodiffusion, ELISA or RNA immunoprecipitation, although there were no significant correlations between anti-Myo 22/25 antibodies and clinical or laboratory findings. There may be a subgroup of PM/DM patients whose sera are positive for anti-Myo 22/25 antibodies.

Adolescent↗

Antibodies to Th/To ribonucleoprotein in patients with localized scleroderma.

OBJECTIVE: Antibodies to Th/To ribonucleoprotein (anti-Th/To) have been detected almost exclusively in patients with systemic sclerosis. Therefore, we aimed to determine the prevalence of anti-Th/To in patients with localized scleroderma. METHODS: Seventy serum samples from patients with localized scleroderma were examined by RNA immunoprecipitation and indirect immunofluorescence analysis using HEp-2 cells as substrate. RESULTS: Three (4%) of 70 sera from patients with localized scleroderma immunoprecipitated 7-2 (Th) RNA and 8-2 (To) RNA. Indirect immunofluorescence analysis demonstrated that all the sera positive for anti-Th/To showed mainly nucleolar staining. In one patient, the coexistence of anti-histone antibody with anti-Th/To was detected by enzyme-linked immunosorbent assay for anti-histone antibody and confirmed using an absorption test with histones followed by indirect immunofluorescence analysis. Moreover, the localized scleroderma patients with anti-Th/To tended to have significantly fewer sclerotic lesions than those without. CONCLUSION: Anti-Th/To is one of the serological abnormalities in localized scleroderma, and the presence of anti-Th/To may be a serological indicator of a mild form of cutaneous involvement.

Antibodies↗

Successful treatment of a patient with lymphomatoid papulosis by methotrexate.

We report a case of lymphomatoid papulosis (LyP) that occurred in a 44-year-old Japanese male patient. Reddish papules with a small number of pustules and nodules were observed on the extremities, chest and upper back. Most lesions were also associated with central necrosis, ulceration and crusting, and regressed spontaneously within 4 to 6 weeks. Histopathological examination revealed wedge-shaped dense cellular infiltrate in the dermis, which was mixed with large atypical lymphoid cells, small lymphocytes, eosinophils and neutrophils. These large atypical cells expressed CD30 on their cell membrane and cytoplasm. Rearrangement of the T-cell receptor (TcR) beta-chain gene was detected in the skin lesion. Lymphadenopathy with histopathologic change similar to the skin lesions, but without TcR gene rearrangement, was found at the left inguinal area. Systemic administration of methotrexate (7.5-15.0 mg/week) was found to be dramatically effective in resolution of skin lesions and prevention of their recurrence.

Adult↗

The successful treatment of prurigo pigmentosa with macrolide antibiotics.

Recent studies have demonstrated that macrolide antibiotics have anti-inflammatory as well as antibacterial effects. Therefore, macrolide antibiotics have been successfully used to treat patients with various inflammatory diseases. We evaluated the effect of macrolide antibiotics in 4 patients with prurigo pigmentosa who were treated with either 400 mg of clarithromycin or 300 mg of roxythromycin daily. Eruption and pruritus disappeared within a week in all the patients while those symptoms were unresponsive to other drugs. Although the mechanism of this effect remains unclear in patients with prurigo pigmentosa, macrolide antibiotics can be considered as an alternative treatment for prurigo pigmentosa.

Adult↗

A case of duodenal involvement of multiple myeloma imaged by positron emission tomography with 18F-fluorodeoxyglucose.

A 61-year-old woman had been treated for multiple myeloma for 4 years when she developed abdominal pain. Ultrasonography and computed tomography revealed a tumor in the abdomen. Positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) showed increased FDG uptake in the tumor. In previous bone marrow lesions, which were in clinical remission after chemotherapy and radiotherapy, abnormal FDG uptake was not recognized. Pathological examination after surgery revealed the tumor to be a plasmacytoma of the duodenum. Plasmacytoma of the duodenum is rare but can be seen during the clinical course of multiple myeloma. A few reports have described FDG PET findings of plasmacytoma. Those previous reports and our present case suggest a potential value of FDG PET in the evaluation of multiple myeloma.

Duodenal Neoplasms↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Serum concentrations of vascular endothelial growth factor in collagen diseases.

Vascular endothelial growth factor (VEGF) is an angiogenic cytokine which has been reported to be important in the pathogenesis of rheumatoid arthritis (RA). In this study, the serum level of VEGF was measured using enzyme-linked immunosorbent assay in 17 patients with systemic lupus erythematosus, 49 patients with polymyositis/dermatomyositis (PM/DM), 40 patients with systemic lupus erythematosus, 49 patients with polymyositis/dermatomyositis (PM/DM), 40 patients with systemic sclerosis (SSc), 11 patients with RA and 20 control subjects. The VEGF level was 184 +/- 62 pg/mL (mean +/- SD) in the serum of normal individuals. The mean VEGF levels in the patients with PM/DM or RA were significantly higher than in the normal controls. In 21 of the 49 patients with PM/DM and nine of the 11 patients with RA, the serum VEGF level was considered to be elevated. In patients with SSc, those with diffuse cutaneous SSc showed elevated VEGF levels in comparison with normal controls. An elevated serum VEGF level was correlated with the frequency of lung fibrosis and reduced vital capacity in the patients with SSc.

Adolescent↗