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T Mimori

Publications and source records attributed to T Mimori.

At least 109 records · Page 6Linked to original sources
PubMed1994

Genetic and immunological differences between Japanese patients with diffuse scleroderma and limited scleroderma.

OBJECTIVE: To study the association between HLA-DR and scleroderma (SSc), subsets of SSc, and autoantibodies in SSc. METHODS: HLA-DR antigens were determined in 45 Japanese patients with SSc. The association between HLA-DR and SSc, subsets of SSc, and autoantibodies was analyzed in 22 patients with SSc excluding mixed connective tissue disease (MCTD)/overlap syndrome (OL). RESULTS: When the 20 patients with MCTD and 3 patients with OL were excluded from the original patient group, a significant increase of HLA-DR2 was observed (59 vs 29% of controls, p < 0.01). The frequency of DR2 increased to 69% in patients with diffuse SSc (p < 0.01). DR1, which was not found in diffuse SSc, was found in 2 of 9 patients with limited SSc. The frequency of DR2 was significantly higher in patients with antitopoisomerase I (10/12, 83%, p < 0.05). In contrast, DR1 was found only in 2 patients with anticentromere antibodies (ACA), and all 5 patients with ACA had no HLA-DR2 (p < 0.01). CONCLUSION: Our results suggest that different HLA-DR markers may be associated with the production of distinct autoantibodies in diffuse SSc and limited SSc.

Antibodies↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1992

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↗
PubMed1992

Ku polypeptides synthesized in vitro assemble into complexes which recognize ends of double-stranded DNA.

The Ku protein is composed of two polypeptide subunits, p70 and p80, and binds DNA ends in vitro. Previous studies suggested that p70 and p80 are physically associated in vivo, although such an association may have been mediated by DNA. We have now utilized full-length Ku polypeptides synthesized in vitro to examine the association of p70, p80, and linear DNA to form a complex. In gel filtration chromatography, p70 migrates as a 70-kDa structure, whereas p80 migrates at 150 kDa. Co-translation of the two cDNAs yields complexes which migrate at 300 kDa and contain equimolar quantities of the p70 and p80 polypeptides, providing direct evidence that p70 and p80 assemble into a complex in the absence of DNA. To demonstrate that this recombinant protein complex binds DNA, we developed a radiolabeled protein electrophoretic mobility shift assay. When radiolabeled proteins synthesized in vitro were incubated with linear DNA and fractionated in a nonreducing, nondenaturing gel, a band representing a complex of p70, p80, and the DNA was seen. Formation of this Ku-DNA complex required free DNA ends, and binding to DNA ends was not observed with individual p70 or p80 subunits. DNA binding was not reconstituted by mixing the individual subunits together. These studies thus demonstrate that it is the complex of p70 and p80, not individual p70 or p80, which possesses the DNA binding properties previously described for native Ku protein. These results provide new information about the assembly, structure, and DNA binding properties of the Ku protein.

Antigens, Nuclear↗
PubMed1992

Autoantibodies to small nuclear and cytoplasmic ribonucleoproteins in Japanese patients with inflammatory muscle disease.

OBJECTIVE: To elucidate the profile and clinical significance of autoantibodies to small nuclear and small cytoplasmic ribonucleoproteins in Japanese patients with polymyositis and dermatomyositis (PM/DM). METHODS: Radioimmunoprecipitation assays were performed with sera from 91 patients with various inflammatory muscle diseases and from 254 control patients with other rheumatic diseases. Patients with PM/DM were categorized according to autoantibody specificities, and clinical comparisons were made. RESULTS: Antibodies to aminoacyl transfer RNA (tRNA) synthetases and the signal recognition particle (SRP) were found to be specific for PM/DM: PM/DM patients with antibodies to 3 aminoacyl-tRNA synthetases (histidyl, threonyl, and glycyl) appeared to form a distinct clinical subset, associated with chronic interstitial lung disease, polyarthritis, and myositis, while 3 patients with antibodies that bound the SRP had severe myositis that was resistant to corticosteroid therapy. In general, the frequency and clinical correlations of anti-aminoacyl-tRNA synthetase antibodies in Japanese patients were similar to those in North American populations. In contrast, among this Japanese cohort, the occurrence of anti-PM/Scl appeared to be reduced in frequency, whereas anti-Ku and anti-U2 RNP antibodies were accentuated in patients with overlap syndromes. CONCLUSION: We conclude that racial groups differ somewhat in their characteristic autoimmune responses to individual autoantigens. These differences could reflect variation in immunogenetic background or different etiologic mechanisms which might occur at different geographic locations.

Asian People↗
PubMed1992

Autoantigenic epitopes of the B polypeptide of Sm small nuclear RNP particles. Identification of regions accessible only within the U1 small nuclear RNP.

OBJECTIVE: To analyze the autoantigenic epitopes of the Sm B polypeptide of the U1 small nuclear RNP (snRNP) using complementary DNA (cDNA) clones. METHODS: Expression of Sm B fusion proteins in lambda phage vectors, immunoblots, immunoprecipitations, and affinity purification of antibodies. RESULTS: Immunoblots using antibodies affinity-purified from B fusion proteins demonstrated that there were cross-reactive epitopes between the B'/B and A polypeptides of the U1 snRNP. Immunoprecipitation assays suggested that there were at least 3 different autoantigenic epitopes on the B polypeptide that could be classified into 2 general groups based upon autoantibody reactivity. The first group of autoantibodies, which bound 2 separate autoantigenic epitopes (BU1-1, BU1-2), participated in immunoprecipitation of the U1 snRNP alone. The second group, which bound the third type of autoantigenic epitope (BSm-1), immunoprecipitated all the abundant Sm snRNPs. CONCLUSION: There is at least 1 region on the B proteins that is accessible to antibodies only within the structure of the U1 snRNP, as well as a region that is accessible on all Sm snRNPs. These data support the notion that the native U1 RNP, perhaps containing B proteins in a different conformation than those found on other Sm snRNPs, may drive the humoral immune response in systemic lupus erythematosus.

Amino Acid Sequence↗
PubMed1992

Nucleotide sequence and genomic structure analyses of the p70 subunit of the human Ku autoantigen: evidence for a family of genes encoding Ku (p70)-related polypeptides.

cDNA encoding the p70 polypeptide subunit of the human Ku autoantigen was isolated. In vitro expression analysis of the cDNA demonstrates that it encodes the entire open reading frame. Nucleotide sequence analysis and comparison to other previously described sequences indicate the existence of several single-nucleotide and amino acid polymorphisms. Southern blot analyses demonstrate the presence of multiple copies of homologous DNA sequences in the human genome. These data support the hypothesis that multiple genes encode a family of Ku(p70)-related polypeptides.

Amino Acid Sequence↗
PubMed1992

Characterization of Trypanosoma cruzi isolates from Paraguay, using restriction enzyme analysis of kinetoplast DNA.

Eleven Paraguayan strains of Trypanosoma cruzi, from Chagas' disease patients and the bug vectors, were examined by restriction endonuclease analysis of kinetoplast DNA using Hae III, Msp I, Eco RI, HinfI, Taq I and Rsa I. Four schizodeme-profile groups were identified. Group 1 had much simpler profiles than groups 2, 3 and 4 and, although there were homogeneous profiles in the latter three groups, each group could be distinguished from the others. The profiles of group 1 could not be matched with any of the standard strains from Brazil, Chile and Columbia included in the schizodeme comparison. The profiles of groups 3 and 4 shared most features with those standards of the Brazilian Z2 zymodeme.

Adolescent↗
PubMed1992

Recurrent annular erythema associated with anti-SS-B/La antibodies: analysis of the disease-specific epitope.

We have found that anti-SS-B/La antibodies are present in a group of patients with a characteristic recurrent annular erythema, and immunological abnormalities. The presence of a disease-specific epitope for this entity has been examined by comparing immunological reactivity of anti-SS-B/La antibodies between these patients and patients with classical Sjögren's syndrome who have anti-SS-B/La antibodies but do not have this characteristic erythema. In immunoblotting using three different antigen sources, all the sera from both groups exhibited the same reaction patterns. V8 protease mapping showed that the sera could be divided into three groups by the difference in reactivity to two main digested peptide fragments. However, no significant relationship of the reactivity in peptide mapping between the two patient groups was observed. Further studies are necessary to elucidate the role of anti-SS-B/La antibodies in disease pathogenesis in these patients, in particular by more precise peptide mapping using recombinant SS-B/La antigen proteins.

Adult↗
PubMed1992

[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↗
PubMed1992

[Spontaneous remission of dermatomyositis which developed one month after normal delivery].

A case of dermatomyositis which developed one month after normal delivery and subsided spontaneously was reported. A 29-year-old woman gave birth to a healthy child. One month later, she noticed muscular pain and weakness of the upper extremities. On admission, there were diffuse edema of upper eyelids with heliotrope rash. The reddish skin rashes were observed on the extensor surfaces of the PIP and MP joints of fingers. Erythrocyte sedimentation rate was 29 mm/hr. The lactic dehydrogenase (LDH), SGOT, CK levels were 470 (normal 150 to 320 IU/l), 43 (normal 6 to 25 IU/l) and 317 (normal 21 to 110 IU/l) respectively. Autoantibodies to nuclear and cytoplasmic antigens were negative. Rheumatoid factor and anti-DNA antibody were negative. Thyroid function was normal. An electromyogram (EMG) demonstrated small amplitude short-duration polyphasic motor unit potentials. The muscle biopsy specimen from left upper arm showed degenerating muscle fibers and infiltration of inflammatory cells surrounding blood vessels. The skin biopsy revealed the presence of edema and perivascular infiltration of lymphocytes. Based on these clinical features and results of various diagnostic tests, a diagnosis of dermatomyositis was established. After the admission, muscle strength has improved dramatically and the CK returned to normal level without specific drug therapy. She has since been seen as an out patient, and complete remission lasted for two years up to date. Review of the literature disclosed that 13 cases of PM/DM which developed during pregnancy or postpartum have been reported including the present case. Detailed analysis showed that these patients were characterized by mild muscular diseases, rare occurrence of internal organ involvements and good response to steroid therapy. As our case, a spontaneous remission was also observed. Although the mechanism involved in occurrence of inflammatory myositis associated with pregnancy or delivery are not clarified, these patient indicated a presence of subset of PM/DM which do not require intensive drug therapy.

Adult↗