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Biomedical subjects

T Tojo

Publications and source records attributed to T Tojo.

At least 91 records · Page 5Linked to original sources

Autoantigenic epitopes on DNA topoisomerase I. Clinical and immunogenetic associations in systemic sclerosis.

OBJECTIVE: To elucidate the clinical and immunogenetic associations with reactivity to autoantigenic epitopes on DNA topoisomerase I (topo I) recognized by sera from patients with systemic sclerosis (SSc). METHODS: Autoantigenic epitopes on topo I were identified by screening an epitope library constructed from topo I complementary DNA restriction fragments using autoimmune anti-topo I-positive sera as a probe. Epitope reactivities of sera from 43 anti-topo I-positive SSc patients were surveyed by immunoblotting, and associations with clinical symptoms and HLA-DR types were examined. RESULTS: Four different epitope regions were identified on the topo I molecule. Immunoreactivity to the region encompassing amino acid residues 658-700, termed ER4, was found to be associated with diffuse cutaneous SSc, progressive pulmonary interstitial fibrosis, and poor prognosis for 15-year survival. SSc patients with ER4 reactivity frequently displayed the DR2/DRw52 phenotype. CONCLUSION: Molecular analysis of precise antigenic epitopes on topo I is helpful in classifying clinical subsets of SSc.

Adult↗

Autoantibody reactive with three classes of RNA polymerases in sera from patients with systemic sclerosis.

We have identified a novel autoantibody reactive with all three classes of RNA polymerases, well-characterized nuclear enzymes, in sera from patients with systemic sclerosis (SSc). After incubation with [35S]methionine-labeled HeLa cell extracts, 14 of 275 SSc sera immunoprecipitated 12 or 14 proteins with similar molecular weights as those of several subunit proteins of eukaryotic RNA polymerases I, II, and III. Purified IgG from these two types of sera inhibited RNA transcription catalyzed by RNA polymerases I, II, and III in vitro. Immunoblot analysis using RNA polymerase-enriched fraction showed that the majority of these sera reacted with 42- or 25-kD protein. Anti-RNA polymerase antibody was highly specific to SSc, especially to diffuse cutaneous SSc. Clinical features associated with this antibody included a high frequency of heart and kidney involvement and a poor survival rate at 5 yr after first visit. These findings indicate that the autoantibody to three classes of RNA polymerases is a new marker for a unique subset of diffuse cutaneous SSc.

Antibodies, Anti-Idiotypic↗

Relationship between autoantibodies and clinical parameters in Sjögren's syndrome.

Glandular function as estimated by salivary function scintigraphy and extraglandular manifestations were compared among 174 Sjögren's syndrome (SS) patients according to their anti-Ro/SSA, anti-La/SSB, and anti-U1RNP autoantibody status, to clarify the relationship between these autoantibodies and clinical parameters in SS. These antibodies were detected by RNA-immunoprecipitation. Anti-La/SSB or only anti-Ro/SSA antibody was common in 84 primary SS (P-SS) patients, whereas the frequency of only anti-U1RNP was high in 90 secondary SS (S-SS) patients, especially in those with systemic lupus erythematosus (SLE). Antibody-negativity was common in SS with rheumatoid arthritis and was also found in 33% of P-SS. In P-SS, salivary gland dysfunction and parotid swelling were severe in patients who had serological abnormalities with anti-Ro/SSA and with or without anti-La/SSB. They were mild in antibody-negative patients who had mild extraglandular symptoms and in patients with only anti-U1RNP antibody who had Raynaud's phenomenon, pulmonary fibrosis, and later disease onset. P-SS patients positive for both anti-Ro/SSA and anti-U1RNP had SLE-like features. SS could be classified clinically according to these autoantibodies.

Autoantibodies↗

Pulmonary pseudolymphoma presented with a mass lesion in a patient with primary Sjögren's syndrome: beneficial effect of intermittent intravenous cyclophosphamide.

A 61-year-old woman with primary Sjögren's syndrome (SS) presented with fever, dry cough, dyspnea on exertion, and a mass lesion with reticular shadowing at both bases on her chest X-ray. Pulmonary pseudolymphoma was diagnosed by transbronchial lung biopsy which revealed infiltration of T cell-like slightly atypical lymphoid cells. After three infusions of cyclophosphamide (750 mg every 4 weeks) combined with prednisolone, the pulmonary mass lesion was diminished and her symptoms improved. Evaluation of the 12 reported cases of pulmonary pseudolymphoma with SS that presented with mass lesions showed an increase in IgM level, frequent pulmonary fibrosis, precedence of SS, and better prognosis with immunosuppressants in those patients.

Biopsy↗

Nonprecipitating IgG or IgM anti-Sm antibody: clinical significance and changes in immunoglobulin class.

OBJECTIVE: To estimate the clinical significance of IgG or IgM nonprecipitating anti-Sm antibodies and their immunoglobulin (Ig) class switch. METHODS: Ninety-one sera which were positive for anti-nRNP antibodies by double immunodiffusion (DID) were obtained from patients with various rheumatic diseases. Anti-Sm antibody was detected by RNA-immunoprecipitation (RNA-IP). IgG or IgM anti-Sm Ig class was measured by enzyme linked immunosorbent assay using affinity purified D polypeptide from HeLa cells. One hundred sixteen clinical manifestations were compared among these groups of patients. RESULTS: By RNA-IP and DID, 91 were divided into 43 with nonprecipitating anti-Sm which were not detected by DID but by RNA-IP, 17 no anti-Sm, and 31 precipitating anti-Sm sera. In 43 patients with nonprecipitating anti-Sm, renal involvement was more common than in no anti-Sm patients. Besides, systemic lupus erythematosus (SLE)-type manifestations were less common than in precipitating anti-Sm patients. In these 43 patients, IgM anti-Sm class was common (13/43). Decrease in the ratio of IgM to IgG anti-Sm antibody was observed in proportion to the years of observation in these patients. IgM anti-Sm predominated in these patients with mixed connective tissue disease (MCTD)-type manifestations while IgG anti-Sm did in those with SLE-type features. CONCLUSIONS: Patients with nonprecipitating anti-Sm who have IgM anti-Sm at early stages of disease are more likely to have MCTD-type manifestations and later may shift to SLE-type features. These may reflect the anti-Sm Ig class switches from IgM to IgG.

Antibodies↗

[Comparison of various methods to close the stump of the main bronchus after pneumonectomy].

In 58 patients who underwent pneumonectomy, the stumps of the main bronchus were sutured manually (by the Sweet method in 13, the Overholt method in 12, and the modified Overholt method in 8) or with machines (TA-30 + S method in 15, TA-30 + O method in 10), and the methods to close the stump were evaluated according to the outcome and postoperative endoscopic findings. Cancer was positive at the stump in 3, and rupture of the membranous portion was observed in 1 in the mechanical suture group. Bronchial fistula was observed in 2 (12%) of the 25 patients in the mechanical suture group but in none of the 33 patients in the manual suture group. The line of closure of the bronchial stump observed by endoscopy was perpendicular to the crest at the tracheal bifurcation in patients sutured by the Sweet or TA-30 + S method, angulated in a chevron shape in many of those sutured by the Overholt method and those sutured by TA-30 + O method, and parallel to the crest in part of those sutured by Overholt method and those sutured by modified Overholt method. The mucosa at the stump was uneven in many patients who showed chevron shaped closure lines. By the modified Overholt method, the wall of the main bronchus could be resected more extensively, the mucosa at the stump was smooth, and the airway lumen showed no marked deformation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Characterization of autoantibodies that recognize U4/U6 small ribonucleoprotein particles in serum from a patient with primary Sjögren's syndrome.

We identified autoantibodies that recognize the U4/U6 snRNPs in a serum from a 63-year-old Japanese patient (TT) with primary Sjögren's syndrome. This patient's serum immunoprecipitated U4 and U6 sn-RNAs exclusively from 32P-labeled HeLa cell extracts and a newly identified 120-kDa protein along with the Sm core proteins (B'/B, D, E, F, and G) from [35S] methionine-labeled HeLa cell extracts. Immunoblotting demonstrated that only the 120-kDa protein was recognized by this unique serum. In glycerol density gradient centrifugation, the 120-kDa protein reactive with TT serum cosedimented with U4 and U6 snRNAs, suggesting that the 120-kDa protein is a unique component of the U4/U6 snRNP particle. In the same study, the U4/U6 snRNP precipitated by TT serum sedimented only in the lower density, whereas anti-Sm antibodies precipitated U4/U6 snRNAs in a broad range of the gradient. This result suggests the presence of at least two molecular forms of the U4/U6 snRNP particles; larger particles, probably the U4/U5/U6 snRNP complex, and free particles. Thus, the U4/U6 snRNP recognized by TT serum includes the U4 and U6 snRNAs, with Sm core proteins, and the novel 120-kDa protein, and appears to be a free particle not associated with larger complexes.

Autoantibodies↗

Specificity of antibodies to single-stranded (ss) DNA in SLE patients with anti-phospholipid syndrome.

Although the concept of anti-phospholipid syndrome has been proposed in patients with SLE and other rheumatic diseases, the immunological mechanism is still controversial. Recently, the crossreactivity between anti-cardiolipin antibody and anti-ssDNA antibodies has been discussed in relation to this syndrome. In the present study, the specificity such as the avidity and the crossreactivity of anti-ssDNA antibodies was examined to find a clue to clarify the question why all of anti-cardiolipin antibody positive patients do not have any specific clinical features, thrombosis and spontaneous abortion. The avidity of IgG anti-ssDNA antibodies was examined by salt elution studies in solid phase ELISA. The avidity of anti-ssDNA antibodies tended to be lower in 10 patients with specific features than in other 10 patients without those features. The crossreactivity of affinity purified IgG anti-ssDNA antibodies was investigated by competitive ELISA. Purified anti-ssDNA antibodies from 4 patients without specific features were slightly inhibited by negatively charged phospholipids, cardiolipin and phosphatidylserine, whereas purified anti-ssDNA antibodies from 2 patients with specific features, who were considered to have anti-phospholipid syndrome, were little inhibited by these phospholipids. The above results suggest that the specificity of anti-ssDNA antibodies appears, at least partly, in different manners whether specific features are present or absent in anti-cardiolipin antibody positive patients. Moreover, anti-ssDNA antibodies and anti-phospholipid antibodies may form separate groups of antibodies in patients with anti-phospholipid syndrome.

Antibody Specificity↗

Initial predictors of survival in patients with systemic sclerosis (scleroderma).

We conducted a retrospective study of 86 patients with systemic sclerosis (SSc) to clarify the initial predictors of survival at the first visit to the hospital. A life-table analysis of survival was performed concerning 137 items from their histories, physical examinations, and laboratory data. The observed cumulative survival rates were 78.0 percent at 5 years and 68.2 percent at 10 years. Ten items were found to be the initial predictors of survival in patients with SSc. Of these 10 items, 9 items showed significant differences within 5 years of the first visit to the hospital. Patients with resting electrocardiographic abnormalities, such as atrial or ventricular arrhythmias, or conduction disturbances, pulmonary fibrosis on the chest x-ray films, or decreased vital capacity had significantly lower survival rates. However, patients with anti-centromere antibody had a significantly better survival rate. In addition, males, aged patients over 65 years old, and patients with proteinuria, leucopenia, or hypergammaglobulinemia had significantly lower survival rates. Only patients with proximal scleroderma at the first visit to the hospital had a significantly lower survival rate after 8 years. These results are useful in predicting individual patients at risk of shortened survival and in managing these patients.

Adolescent↗

[Application of an expandable metallic Z-type stent for stenosis of the left main bronchus following tuberculosis--a case report].

A 32-year-old man had been suffering from dyspnea on exertion and stridor, which were due to stenosis of the left main bronchus as a complication of bronchial tuberculosis. A three-connection stent, 1.2 cm in diameter and 4.5 cm in length was placed at the site of the bronchial stenosis. Dyspnea disappeared 2 days after the procedure, and the pulmonary function 3 weeks later showed considerable improvements in %FVC, FEV1 and MMF.

Adult↗

[Clinical significance of anti-nucleolar antibodies detected by immunoprecipitation method in patients with systemic sclerosis].

We have characterized a clinical significance of anti-U3RNP, anti-7-2RNP, anti-RNA polymerase I and anti-PM-Scl antibody, autoantibodies to nucleolar proteins detected by immunoprecipitation method in patients with systemic sclerosis (SSc). In 248 patients with SSc, anti-U3RNP antibody was positive in 9 (3.6%), anti-7-2RNP antibody was positive in 7 (2.8%) and anti-RNA polymerase I antibody was positive in 3 (1.2%). But none of 248 patients was positive for anti-PM-Scl antibody. Anti-U3RNP antibody positive SSc patients showed significantly lower frequency of joint and lung involvements, compared with anti-U3RNP antibody negative SSc patients. Anti-7-2RNP antibody was found only in patients with limited scleroderma. The anti-7-2RNP antibody could be detected before appearance of skin thickening, so this indicate the usefulness of detecting anti-7-2RNP antibody in the early stage of SSc. Two of 3 anti-RNA polymerase I antibody positive patients were classified as diffuse scleroderma. All anti-RNA polymerase I antibody positive patients had high incidence of internal organ involvements including lung, heart and kidney, so two of these patients died of heart failure. These data showed the close clinical association of antigenic specificities of anti-nucleolar antibodies analysed by immunoprecipitation method, and indicated the usefulness of detecting these anti-nucleolar antibodies in subgrouping of patients with SSc.

Adult↗

Repeated intestinal ulcerations in a patient with systemic lupus erythematosus and high serum antiphospholipid antibody levels.

We report the case of a patient with SLE who had repeated ulceration of the small intestine requiring emergency surgery. Pathologic examination revealed microthrombosis and vasculitis at the site of the intestinal ulcers. High levels of antiphospholipid antibodies, thrombocytopenia, and prolonged prothrombin time coincided with the episodes of intestinal ulceration. Antiphospholipid antibodies may be involved in the development of thrombosis resulting in the repeated episodes of intestinal ulceration in this patient. This possibility should be considered in patients with SLE who have intestinal ulceration and appropriate antithrombotic medication should be administered.

Adult↗