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T Mimori

Publications and source records attributed to T Mimori.

At least 73 records · Page 4Linked to original sources
PubMed1997

[Antigenic epitopes recognized by autoantibodies to calpastatin in patients with rheumatoid arthritis and their clinical significance].

We have previously described that novel autoantibodies to calpastatin (endogenous inhibitor for calcium-dependent neutral protease, calpain) were detected in patients with rheumatoid arthritis (RA) and other disorders. Since calpain is thought to mediate inflammatory process and cartilage destruction, autoantibodies to its inhibitor protein, calpastatin, may be involved in the pathogenic mechanism of rheumatoid arthritis. In the present study, we analyzed antigenic epitopes reactive with autoantibodies to calpastatin and their clinical correlation. cDNA encoding the C-terminal 178 amino acids of human calpastatin (RA-6) was digested by restriction enzymes and ligated in to pEX expression vectors. These recombinant plasmids were tranfected into E. coli POP2136 and screened by colony blots using RA sera containing anticalpastatin antibodies and a mouse monoclonal antibody. RA patient sera recognized the C-terminus of domain IV (epitope C1 ; aa. 647-673) and C-terminus of domain III (epitope C2 ; aa. 496-571), whereas the mouse monoclonal antibody recognized an entirely different region containing the calpain-binding site (epitope B2 ; aa. 572-625). To evaluate epitope reactivity of patient autoantibodies, 15 RA sera containing anti-calpastatin were reacted with epitope fusion proteins. In immunoblotting, most RA sera recognized either C1 or C2 epitopes (67% and 40%, respectively), and only one patient recognized both epitopes. B2 epitope a more progressed and sever state of arthritis than those not reacting with C1. These results suggests that anti-calpastatin antibodies may play a role in the pathogenic mechanisms of RA and their epitope reactivity may be important for disease progression.

Adult↗
PubMed1997

[Successful treatment of toe gangrene with moderate-dose steroid therapy in a patient with systemic sclerosis (CREST syndrome)].

A 68-year-old woman first noticed Raynaud's phenomenon at the age of 35, and she was diagnosed as having systemic sclerosis (SSc) because of cutaneous calcinosis, sclerodactyly, telangiectasia, sausage-like finger, digital pitting scar in 1971. In October, 1994, she was suffered from cold sensation in her right foot, and on November 2 she noticed the painful ulcers on the right toe, which progressed to be gangrenous. Every antiplatelet or thrombolytic agents including PGE1, argatroban, sarpogrelate hydrochloride and urokinase were unsuccessful. Angiograms revealed marked narrowing of bilateral anterior and posterior tibial and peroneal arteries. Prednisolone 30 mg/day was started, which resulted in successful response within 10 days. Large vessel involvement in SSc patients has been reported to be rare, and its treatment remains to be established. We believe our case help understanding the pathophysiology of such rare manifestation in SSc.

Aged↗
PubMed1997

[Novel autoantibodies that recognize native transfer RNAs in patients with systemic rheumatic diseases].

Autoantibodies directed against aminoacyl-tRNA synthetases are well described in adult polymyositis/dermatomyositis. However, the characteristics of antibodies against other tRNA and tRNA-associated proteins have not been well defined. In this study, we identified novel autoantibodies to total tRNAs in patients with systemic rheumatic diseases and characterized the structure that was recognized by anti-tRNA antibodies. We identified fifteen patients sera that immunoprecipitated the deproteinized cognate tRNA. Two of them were identified as having previously well-defined anti-PL-12 antibodies. Three of the remaining 13 patient sera immunoprecipitated naked tRNA of E. coli. To investigate the antibody binding site on tRNAs, we have used in vitro transcripts from cDNAs encoding wild type tRNAs of E. coli and their synthesized mutants. These sera revealed different reactivity to mutated tRNAs. Eleven of these 13 patients met disease specific criteria for: SLE (3 patients), Sjögren's syndrome (6), or SLE/Sjögren's syndrome overlap (2). In addition, fever, Raynaud's phenomenon, and non-erosive polyarthritis, were frequently found in these patients. In summary, we have identified novel antibodies to tRNAs which appear to be quite common, and distinct from previously described anti-aminoacyl-tRNA synthetase antibodies.

Adult↗
PubMed1997

Clinical characteristics of patients with rheumatoid arthritis and methotrexate induced pneumonitis.

OBJECTIVE: To determine the clinical features of methotrexate (MTX) pneumonitis in patients treated for rheumatoid arthritis (RA). METHODS: The medical records of 284 patients with RA who had been treated with oral MTX (mean followup 33.2 mo) were reviewed retrospectively. RESULTS: MTX induced interstitial pneumonitis developed in 6 patients (2.1%). The affected patients were significantly older than those without MTX pneumonitis (67.3 +/- 9.8 vs 52.4 +/- 12.6 yrs, respectively; p < 0.005). The cumulative MTX dose ranged from 65 to 580 mg at the time pneumonitis developed. Five of the patients (83%) had preexisting interstitial abnormalities, while only 29 of the 278 patients without MTX pneumonitis (10%) had such abnormalities (p < 0.001). The frequency of adverse effects due to previous treatment with disease modifying antirheumatic drugs (DMARD) was 66.7% in MTX pneumonitis patients and 14.3% in the other 278 patients (p < 0.01). CONCLUSION: Advanced age, preexisting interstitial abnormalities, and previous adverse reactions to DMARD may be associated with MTX pneumonitis. Patients with these characteristics require careful monitoring during MTX therapy.

Adult↗
PubMed1997

An outbreak of ascariasis with marked eosinophilia in the southern part of Kyushu District, Japan, caused by infection with swine ascaris.

Ascariasis has been a representative soil-transmitted intestinal parasitic disease in warm climates. In Japan, this disease was a major and serious public health problem only a few decades ago. However, the incidence of the disease nowadays is reportedly less than 0.01%. Recently in 1994 through 1995, we experienced a total of 14 cases who were suspected as having ascariasis. They were characterized by peripheral blood eosinophilia (30-70%), high serum titers against Ascaris antigen, and most notably, they were absolutely negative for Ascaris eggs in repeated fecal examinations. Specific antibody titers against Ascaris antigen correlated well with the degree of eosinophilia. All patients were living in narrow areas of Kyushu, Japan, where a lot of porcine farms were located. Most of the patients were asymptomatic and pointed out to have eosinophilia during follow-up studies of chronic diseases or in regular check-up. Only one patient had a clear sign of Löffler's syndrome and another had subcutaneous eosinophilic granuloma. However, laboratory examinations revealed moderate liver dysfunction in 7 patients and pulmonary infiltrations in 5 patients. Based on circumstantial and serological evidence, these patients were diagnosed as having been infected with Ascaris lumbricoides suum, a swine Ascaris.

Adult↗
PubMed1996

Chromosomal localization of the mouse and rat DNA double-strand break repair genes Ku p70 and Ku p80/XRCC5 and their mRNA expression in various mouse tissues.

The Ku p70 and Ku p80/XRCC5 genes are involved in DNA double-strand break repair and V(D)J recombination, and their gene products are the components of the DNA-dependent protein kinase. We have determined the chromosomal locations of the mouse Ku p70 and Ku p80/XRCC5 genes by both in situ hybridization and molecular linkage analysis: the Ku p70 gene was localized to mouse chromosome 15 and rat chromosome 7, and the Ku p80/XRCC5 gene was localized to mouse chromosome 1 and rat chromosome 9. Both genes were mapped to a region of conserved linkage homology among three species, i.e., the mouse, rat, and human. Molecular linkage analysis using interspecific backcross mice revealed that the murine Ku p70 locus was localized 0.7 cM terminal to D15Mit1 and that the murine Ku p80/XRCC5 locus was 0.7 cM proximal to D1Mit46. To determine the size and tissue transcription specificity of the mouse Ku p70 and Ku p80/XRCC5 mRNA, Northern blot analysis was carried out with six mouse tissues. Each tissue expressed one species of the Ku p70 gene transcript with 2.4 kb and one species of the Ku p80/XRCC5 gene transcript with 2.6 kb. In the latter case, however, the brain showed two sizes of transcript, 2.6 and 2.9 kb.

Animals↗
PubMed1996

Sp1 family proteins recognize the U5 repressive element of the long terminal repeat of human T cell leukemia virus type I through binding to the CACCC core motif.

We have identified several nuclear proteins binding to the U5 repressive element (U5RE) at the U5 region of the human T cell leukemia virus type I (HTLV-I) long terminal repeat (LTR). In gel mobility shift assays with the U5RE DNA probe, Jurkat T cell nuclear proteins generated five different complexes, named U5RE binding protein complexes (U5RP)-A1, -A2, -A3, -B, and -C. Only U5RP-C was affected by pretreatment with an excess of poly(dI-dC) and was immunodepressed by anti-Ku/p80 antibodies, suggesting that U5RP-C is a nonspecific complex involving Ku antigen. UV cross-linking showed at least six nuclear proteins involved in the other complexes, including U5RP-A1, -A2, -A3, and -B. The sequence of the binding core element of these specific complexes, determined by competition assays and gel mobility shift assays using a series of the U5RE mutants, is CACCC which is identical to that for the Sp1 transcription factor. LTR with a mutant U5RE, which has no ability to bind with the nuclear proteins, showed stronger promoter activity than LTR with the wild U5RE, suggesting that the specific interaction of these U5RE-binding proteins might result in the U5-mediated repression. U5RP-A1 was supershifted by anti-Sp1 antibodies and U5RP-A2 and -B were supershifted by anti-Sp3 antibodies, suggesting that Sp1 or Sp3 is involved in U5RP-A1 or U5RP-A2 and -B, respectively. Although the other nuclear proteins remain to be characterized, these findings suggest that U5RE-binding proteins in U5RP-A1, -A2, -A3, and -B are involved in HTLV-I gene repression.

Base Sequence↗
PubMed1996

The interaction between Ku antigen and REF1 protein mediates negative gene regulation by extracellular calcium.

Through the specific binding of a negative calcium-responsive element to its binding protein in response to extracellular Ca (Ca2+e), negative calcium-responsive element-bearing genes, such as the human parathyroid hormone gene, are negatively regulated by Ca2+e. The Ku antigen mediated negative gene regulation by Ca2+e by interacting with a redox factor protein, REF1. Although sequence-nonspecific DNA binding activity of the Ku antigen has been well characterized, the mechanism of its sequence-specific DNA binding remained obscure. Here, we report that the specific binding of the Ku antigen to another protein, REF1, leads to DNA-protein complex formation with a novel sequence specificity and thereby regulates gene expression.

Amino Acid Sequence↗
PubMed1996

Autoantibodies to DNA-dependent protein kinase. Probes for the catalytic subunit.

DNA-dependent protein kinase (DNA-PK) is an important nuclear enzyme which consists of a catalytic subunit known as DNA-PKcs and a regulatory component identified as the Ku autoantigen. In the present study, we surveyed 312 patients in a search for this specificity. 10 sera immunoprecipitated a large polypeptide which exactly comigrated with DNA-PKcs in SDS-PAGE. Immunoblot analysis demonstrated that this polypeptide was recognizable by a rabbit antiserum specific for DNA-PKcs. Although the patient sera did not bind to biochemically purified DNA-PKcs in immunoblots or ELISA, they were able to deplete DNA-PK catalytic activity from extracts of HeLa cells in a dose-dependent manner. We conclude that these antibodies should be useful probes for studies which aim to define the role of DNA-PK in cells. Since six sera simultaneously contained antibodies to the Ku protein, these studies suggest that relatively intact forms of DNA-PK complex act as autoantigenic particles in selected patients.

Antigens, Nuclear↗
PubMed1996

Enhancement of anti-DNA topoisomerase I autoantibody response after lung cancer in patients with systemic sclerosis. A report of two cases.

Anti-DNA topoisomerase I (anti-topo I) antibody profiles were compared before and after lung cancer in 2 patients with systemic sclerosis (SSc). Both patients developed adenocarcinoma of the lung late in the course of SSc and died of the cancer. Anti-topo I antibody levels, determined by double immunodiffusion and enzyme-linked immunosorbent assay, increased markedly at the time of diagnosis of lung cancer. Furthermore, patients' sera obtained after lung cancer reacted with multiple epitopes on the entire topo I molecule, some of which had not previously been recognized. These results further support the concept that anti-topo I antibody production in SSc patients is due to an antigen-driven process.

Adenocarcinoma↗
PubMed1996

Novel autoantibodies directed against the common tertiary configuration of transfer RNA in a patient with interstitial lung disease.

OBJECTIVE: To identify and characterize a novel autoantibody, anti-WS, that binds total transfer RNA (tRNA). METHODS: Serum from patient WS, who had polyarthritis, Sjögren's syndrome, Raynaud's phenomenon, and interstitial pulmonary fibrosis, was used in this study. Characteristics of anti-WS and antibody-reactive determinants of tRNA were investigated by 32P immunoprecipitation using HeLa cell RNA and deletion mutants of tRNA transcribed in vitro. RESULTS: WS serum produced nucleolar and cytoplasmic staining on indirect immunofluorescence. 32P immunoprecipitation assays demonstrated that this serum immunoprecipitated total tRNAs and 5.8S and 5S ribosomal RNAs from 32P-labeled HeLa cell extract. When deproteinized RNA was used as antigen source, total tRNAs were still precipitated by WS serum. An immunoprecipitation study, using various deletion mutants of Escherichia coli tRNA, demonstrated that both D and T psi C loops were needed for antibody binding. Substitution of nucleotide 18G with 18A of E coli tRNA(Trp), which is essential in the formation of the tertiary "L" shape of tRNA, inhibited binding by anti-WS antibodies. CONCLUSION: Anti-WS antibodies are novel autoantibodies directed against tRNAs. The antibody binding site is the common L-shaped tertiary structure conformed by the D loop and T psi C loop of tRNA, suggesting that the antibodies are induced by a conserved sequence among all species. Furthermore, these antibodies could be a marker for a newly recognized subset of connective tissue disease.

Autoantibodies↗
PubMed1996

Detection of autoantibodies to nucleolar transcription factor NOR 90/hUBF in sera of patients with rheumatic diseases, by recombinant autoantigen-based assays.

OBJECTIVE: We attempted to clarify the clinical characteristics of Japanese patients with autoantibodies to nucleolar transcription factor NOR 90/hUBF (anti-NOR 90) and to analyze the autoantigenic epitopes recognized by anti-NOR 90. METHODS: Ninety-one patient sera containing anti-nucleolar antibodies (ANoA) by indirect immunofluorescence were collected. Immunoblottings were performed using recombinant fusion proteins expressed from several cloned complementary DNA (cDNA) encoding the NOR 90/hUBF autoantigen. RESULTS: Anti-NOR 90 were detected in sera from 9 (9.9%) of 91 patients with ANoA. Seven of these patients were diagnosed as having Sjögren's syndrome, 4 had concomitant rheumatoid arthritis, 1 had concomitant systemic sclerosis (SSc), and 2 had SSc alone. All 9 sera were reactive with more than 2 recombinant fusion proteins from cDNA encoding separate regions on the hUBF polypeptide. CONCLUSION: The results suggest that while anti-NOR 90 antibodies are rare, they are associated with Sjögren's syndrome in Japanese patients, and that autoimmunity is targeted toward at least 2 separate regions (amino acids 89-310 and 310-633) of the hUBF polypeptide.

Aged↗
PubMed1996

Interrelationship of major histocompatibility complex class II alleles and autoantibodies in four ethnic groups with various forms of myositis.

OBJECTIVE: To examine interrelationships among myositis subsets, autoantibodies, and major histocompatibility complex (MHC) class II alleles across ethnic lines, and to localize genetic susceptibility (presence of HLA-DR versus DQ) to myositis within the MHC class II region. METHODS: MHC class II alleles (HLA-DRB1, DQA1, and DQB1, detected by DNA oligotyping) and myositis-specific autoantibodies (MSA) were determined in 224 patients with various myositis syndromes, including 89 whites, 89 African-Americans, 25 Mexican-Americans, and 21 Japanese. RESULTS: Anti-Jo-1 (histidyl-transfer RNA [tRNA] synthetase) and other MSAs (anti-PL-12, anti-PL-7, anti-OJ, anti-EJ, anti-KJ, anti-tRNA, and anti-signal recognition particle) were equally distributed among the races, but occurred more often in patients with polymyositis (PM) than in those with dermatomyositis (DM) or other myositis syndromes. MSA frequencies were significantly positively associated with anti-Ro (SS-A) (P = 0.002), and significantly negatively associated with anti-U1 RNP (P = 0.003). Frequencies of the HLA-DRB1*0301 (DR3), DQA1*0501, and DQB1*0201 (DQ2) alleles (and haplotype) were each increased in white patients with myositis, especially those with PM, but most strikingly in those with MSAs. However, in the other ethnic groups, except the Japanese group, only frequencies of HLA-DQA1*0501 and the structurally similar DQA1*0401 alleles were significantly increased. The presence of HLA-DQA1*0501 or *0401 was most significantly associated with anti-Jo-1, anti-PL-12, and other MSAs, compared with myositis patients without MSAs (P = 0.0008, Pcorr = 0.01, odds ratio [OR] = 3.7), and with normal, ethnically matched controls (P = 3 x 10(-7), Pcorr = 1 x 10(-6), OR = 6.5). Among MSA-positive patients who were negative for HLA-DQA1*0501 and *0401, including Japanese patients, the HLA-DQA1*0102 and *0103 alleles predominated. In addition, there appeared to be a negative association of the HLA-DR2 alleles (DRB1*1501 and *1503) with PM (P = 0.007, Pcorr not significant, OR = 0.39), but not with DM or myositis overall. CONCLUSION: By transracial gene mapping, genetic susceptibility to anti-Jo-1 and other MSAs in patients with myositis can be localized within the MHC region to the HLA-DQA1 locus.

Adult↗
PubMed1996

Anti-U5 small nuclear ribonucleoprotein (snRNP) antibodies: a rare anti-U snRNP specificity.

We surveyed for autoantibodies to the U small nuclear ribonucleoproteins (snRNPs) in sera from 1171 patients with various connective tissue diseases by immunoprecipitation assay. We found serum, termed LaJ, which principally recognized the U5 snRNP from one patient with systemic sclerosis-polymyositis overlap syndrome. Anti-LaJ serum immunoprecipitated predominantly U5 snRNA from a 32PO4-labeled HeLa cell extract and at least five U5-specific proteins as well as the Sm core proteins from a [35S]methionine-labeled extract. Anti-LaJ serum immunoprecipitated both U5 snRNA and these five proteins in identical fractions at 15-20S by parallel sucrose gradient, suggesting physical association of these two components. Thus, we concluded that anti-LaJ serum contained antibody specific to the U5 snRNP. Antibodies specific to U5 snRNP were found in a single serum; in contrast, the prevalence of anti-U1 snRNP and anti-Sm antibody was considerably higher. Thus, the specific proteins of the U5 snRNP are rare targets for autoantibodies in patients with connective tissue disease.

Antibodies, Antinuclear↗
PubMed1996

Structures targeted by the immune system in myositis.

Polymyositis and dermatomyositis are characterized by the production of a series of autoantibodies to various cellular constituents. Some of these autoantibodies are found specifically in patients with polymyositis or dermatomyositis or myositis overlap syndrome and predict clinical subgroups and prognosis. If we are to understand the etiology and pathogenic mechanisms of polymyositis and dermatomyositis, it will be particularly important to elucidate the structure and function of target autoantigens recognized by these myositis-specific autoantibodies. In recent years, many autoantigens and some epitopes have been identified using molecular biology approaches. During the 1-year period reviewed here, the nature and function of the Mi-2 and the Ku(p70/p80) antigens which are recognized by autoantibodies in patients with dermatomyositis and with the myositis overlap syndrome, respectively, have been elucidated. Several new autoantibodies that are not specific for but that are associated with myositis have also been described.

Amino Acyl-tRNA Synthetases↗