Identification of a DRB1*0405 variant (DRB1*04052) using the PCR-RFLP method.
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Alleles↗
Biomedical subjects
T Mimori
Publications and source records attributed to T Mimori.
Successful treatment with cyclosporin A of pure red cell aplasia associated with rheumatoid arthritis.
We describe the first report of a patient with rheumatoid arthritis (RA) who developed refractory pure red cell aplasia that was successfully treated with cyclosporin A (CyA). Since no inhibitory activity against bone marrow was observed in the whole serum, it is possible that the clinical efficacy of CyA on both RA and aplasia was explained by its effects on T cells that might be involved in the development of these diseases.
Arthritis, Rheumatoid↗
[Two cases of interstitial pneumonia with anti-PL-12 (alanyl tRNA synthetase) antibodies].
We present two cases of interstitial pneumonia (IP) whose sera contain autoantibodies to PL-12 (alanyl tRNA synthetase). The first patient is a 47-year-old female who was diagnosed as IP and treated with corticosteroid at another hospital. She was admitted to Keio University Hospital due to worsening of dyspnea and polyarthritis. Laboratory studies revealed elevation of LDH and CRP, and her chest radiography showed interstitial fibrosis. Because of clinical deterioration, the dose of corticosteroid was increased (prednisolone 40 mg/day) and her symptom was stabilized. The second patient, a 55 year-old female, was admitted to Tokyo Metropolitan Ohtsuka Hospital because of dyspnea on exertion and polyarthritis. She did not show any symptom of myositis and was diagnosed as IP with arthritis on the basis of her clinical and chest radiography. She was treated with oral corticosteroid (prednisolone 30 mg/day), which resulted in improvement of her respiratory symptom and arthritis. Both patients were found to have autoantibodies to the PL-12. Autoantibodies to aminoacyl tRNA synthetases have been recognized as having a linkage with myositis mainly because of observations of the Jo-1 specificity. There was one report on a North American population that most but not all patients with anti-PL-12 antibodies had myositis. However, the clinical significance of anti-PL-12 has not been examined in Japanese patients. These patients suggested that anti-PL-12 antibodies have a stronger association with IP than myositis in Japanese patients.
Alanine-tRNA Ligase↗
[Case of MPO-ANCA positive interstitial pneumonitis and necrotizing, crescentic glomerulonephritis].
A 52-year-old man was admitted to our hospital in July 1995, because of intermittent claudication, paresthesia on foot and gross hematuria. Chest radiograph in 1988 revealed bilateral interstitial shadows and proteinuria had been pointed out since 1992. On admission, chest X-ray and computed tomography showed diffuse interstitial shadow, however it had not been changed for several years. Laboratory tests revealed elevated level of erythrocyte sedimentation rate, C-reactive protein, immunoglobulin, rheumatoid factor, IgG-rheumatoid factor, and immune complex. Serum MPO-ANCA were positive. Although serum creatinine level and renal function test were normal, renal biopsy demonstrated crescentic formation and necrotizing vasculitis. Immunofluorescence and electron microscopy demonstrated no remarkable deposit in glomerulus. A diagnosis of microscopic polyarteritis necrotizing and crescentic glomerulonephritis (NCGN) was made. Treatment was initiated with 30 mg of prednisolone, followed by marked improvement of intermittent claudication, and decreased titer of serum MPO-ANCA. Previous reports have demonstrated the association of MPO-ANCA with rapidly progressive NCGN, microscopic polyarteritis, and occasionally pulmonary hemorrhage recognized as pulmonary-renal syndrome. However, the present case suggests the possibility that another disease subset may also be associated with MPO-ANCA, which is characterized by interstitial pneumonitis and slowly progressive glomerulonephritis.
Antibodies, Antineutrophil Cytoplasmic↗
Autoantibodies to calpastatin (an endogenous inhibitor for calcium-dependent neutral protease, calpain) in systemic rheumatic diseases.
We identified an autoantibody that reacts with calpastatin [an inhibitor protein of the calcium-dependent neutral protease calpain (EC 3.4.22.17)]. In early immunoblot studies, sera from patients with rheumatoid arthritis (RA) recognized unidentified 60-, 45-, and 75-kDa proteins in HeLa cell extracts. To identify these autoantigens, we used patient sera to clone cDNAs from a lambda gt11 expression library. We isolated clones of four genes that expressed fusion proteins recognized by RA sera. The 1.2-kb cDNA insert (termed RA-6) appeared to encode a polypeptide corresponding to the 60-kDa antigen from HeLa cells, since antibodies bound to the RA-6 fusion protein also reacted with a 60-kDa HeLa protein. The deduced amino acid sequence of the RA-6 cDNA was completely identical with the C-terminal 178 amino acids of human calpastatin except for one amino acid substitution. Patient sera that reacted with the RA-6 also bound pig muscle calpastatin, and a monoclonal antibody to human calpastatin recognized the RA-6 fusion protein, confirming the identity of RA-6 with calpastatin. Moreover, the purified RA-6 fusion protein inhibited the proteolytic activity of calpain, and IgG from a serum containing anti-calpastatin antibodies blocked the calpastatin activity of the RA-6 fusion protein. Immunoblots of the RA-6 product detected autoantibodies to calpastatin in 57% of RA patients; this incidence was significantly higher than that observed in other systemic rheumatic diseases, including systemic lupus erythematosus (27%), polymyositis/dermatomyositis (24%), systemic sclerosis (38%), and overlap syndrome (29%). Thus, anti-calpastatin antibodies are present most frequently in patients with RA and may participate in pathogenic mechanisms of rheumatic diseases.
Amino Acid Sequence↗
Changing autoantibody profiles with variable clinical manifestations in a patient with relapsing systemic lupus erythematosus and polymyositis.
The production of autoantibodies characteristic of different autoimmune disease subsets is thought to be controlled primarily by genetic factors, whereas non-genetic factors are generally believed to be of secondary importance. A patient with systemic lupus erythematosus (SLE) and polymyositis (PM) who experienced frequent relapses associated with changing clinical manifestations and autoantibody specificities is reported. Her initial presentation as SLE with anti-Sm antibodies shifted to the onset of PM with temporal production of a different set of autoantibodies. The latter antibodies disappeared when myositis resolved, followed by the reappearance of autoantibodies and clinical manifestations characteristic of SLE. The shifts of autoantibody profiles in association with variable clinical manifestations in this patient argue that environmental factors may play a more important role in autoimmunity than previously supposed, and that interplay between environmental triggers and genetic predisposing factors may lead to the constellation of autoimmune disease manifestations exhibited at a particular time.
Adult↗
[A case of adult onset Still's disease complicated with adult respiratory distress syndrome and disseminated intravascular coagulation].
A 71 year-old man with adult onset Still's disease was admitted to our hospital because of fever, sore throat, myalgia and macular nonpruritic salmon pink eruption. He was treated with prednisolone, 40 mg daily and these symptoms disappeared. When the dose of prednisolone was reduced to 30 mg daily, he began to notice fever. 5 days later he developed adult respiratory distress syndrome (ARDS). The dose of prednisolone was increased to 50 mg daily and oxygen administration was started. All symptoms began to improve immediately and the dose of prednisolone was decreased to 40 mg daily. 10 days later he noticed fever and skin rash. Laboratory investigation showed platelet counts of 69,000/mm3, a ferritin of 37,000 ng/ml, and increased fibrinogen degradation product, indicating increased activity of adult onset Still's disease associated with disseminated intravascular coagulation (DIC). The dose of prednisolone was again increased to 60 mg daily, and 100 mg of nafamostat mesilate was administrated intravenously. All above symptoms associated with adult onset Still's disease and DIC disappeared. The dose of prednisolone was gradually decreased and the clinical course was uneventful with daily administration of 10 mg of prednisolone. Although there are a couple of case report which described the association of adult onset Still's disease with either ARDS or DIC, the association of adult onset Still's disease with both ARDS and DIC have not been reported yet.
Aged↗
[Three cases with systemic rheumatic diseases who developed pulmonary lesions suggestive of bronchiolitis obliterans organizing pneumonia].
Three cases with systemic rheumatic diseases who developed lung diseases compatible with BOOP were reported. Underlying diseases of these patients were: RA (1 case), SLE (2 cases). Respiratory symptoms were observed in one case such as dry cough at the time of diagnosis of BOOP. Chest radiography showed multiple infiltrates in 2 cases, bilateral reticular shadow in one case. In one case characteristic finding described as wandering shadow was observed. TBLB was done in 3 cases. Pathohistological findings were compatible with BOOP. Repeated Bacteriological examinations failed to demonstrate specific organisms implicated for lung lesions. Cytological studies of sputum and TBLB specimens were all negative for malignancy. Antibiotic agents including anti-tuberculosis drugs were not effective for pulmonary diseases. Moderate doses of prednisolone were effective in 3 cases. Although the open lung biopsy has been recommended for establishment of diagnosis of BOOP, in patient with systemic rheumatic diseases this invasive procedure is not always easily performed. Further characterizations of clinical and laboratory features are indicated for noninvasive diagnosis of BOOP.
Adult↗
[Interstitial lung disease in patients with connective tissue diseases].
Interstitial lung disease is a significant prognostic factor in connective tissue diseases. To further clarify clinical and immunological features of interstitial lung disease, we studied 894 consecutive patients with connective tissue diseases first evaluated between 1970 and 1993. Interstitial lung disease was found in 101 of 181 (56%) patients with systemic sclerosis, 92 of 183 (50%) with overlap syndrome, 35 of 76 (46%) with polymyositis/dermatomyositis, and 13 of 444 (3%) with systemic lupus erythematosus (p < 0.05, systemic lupus erythematosus vs. other connective tissue diseases). The presence of interstitial lung disease correlated with decreased survival in systemic sclerosis and in polymyositis/dermatomyositis, but not in overlap syndrome or in systemic lupus erythematosus. Interstitial lung disease in patients with connective tissue diseases was classified into two types: acute (n = 8) and chronic (n = 233). Among the 8 patients with acute disease, 4 (all with dermatomyositis) died of respiratory failure and 3 (all with systemic lupus erythematosus) responded to corticosteroids. Among the 233 patients with chronic interstitial lung disease, 20 had polymyositis/dermatomyositis with anti-aminoacyl tRNA synthetase antibodies and 40 had overlap syndrome with anti-U1 RNP antibodies. Respiratory failure in these patients was not frequent and occurred late in the course of the disease. As a cause of death, respiratory failure was associated with autoantibodies to topoisomerase I and aminoacyl tRNA synthetase but not anti-U1 RNP. Autoantibodies to aminoacyl tRNA synthetases were detected before the development of interstitial lung disease in 9 patients with polymyositis/dermatomyositis. We conclude that the clinical features of interstitial lung disease associated with connective tissue diseases vary with the type of connective tissue disease, and that analysis of autoantibodies can be useful in establishing a diagnosis and in forecasting the course and outcome.
Adult↗
Autoantigen Ku protein is involved in DNA binding proteins which recognize the U5 repressive element of human T-cell leukemia virus type I long terminal repeat.
We have identified and analyzed a 27-nucleotide sequence (U5 repressive element, designated as U5RE) at the U5 region of the human T-cell leukemia virus type I (HTLV-I) long terminal repeat (LTR) which is required for HTLV-I basal transcriptional repression. The basal promoter strength of constructs that contained deletions in the U5 region of the LTR was analyzed by chloramphenicol acetyltransferase (CAT) assays following transfection of HeLa cells or Jurkat T-cells in the presence or absence of viral transactivator tax protein. We consistently observed a 2- to 5-fold increase in basal promoter activity when sequences between +277 to +306 were deleted. In vivo competition experiments suggested that the U5 DNA fragment from +269 to +295 contains a functional repressive element (U5RE). Using gel mobility shift assays, we have purified a highly enriched fraction that could specifically bind U5RE. This DNA affinity column fraction contained three major detectable proteins on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with silver staining: 110-, 80- and 70-kDa proteins. The 110-kDa protein appeared to be a novel DNA-binding protein whose characteristics are still obscure, while the 70- and 80-kDa proteins were shown to be related to the human autoantigen Ku, the Ku (p70/p80) complex, as demonstrated by amino acid sequencing and immunological analyses. As Ku is known to be involved in transcriptional regulation, the specific interaction of Ku with U5RE raises intriguing possibilities for its function in HTLV-I basal transcriptional repression.
Amino Acid Sequence↗
[Diagnosis and therapy of hypertrophic osteoarthropathy].
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Anti-Inflammatory Agents, Non-Steroidal↗
Molecular properties, substrate specificity and regulation of DNA-dependent protein kinase from Raji Burkitt's lymphoma cells.
A double-stranded DNA-dependent protein serine/threonine kinase (DNA-PK) was purified from a nuclear extract of Raji Burkitt's lymphoma cells by a three-step column-chromatographic procedure. The main silver-stained band visualized after SDS/PAGE corresponded to an autophosphorylated polypeptide of about 350-kDa that represents the catalytic component. The existence of Ku DNA-binding protein as a regulatory component in the purified enzyme was revealed by Western blot/enzyme immunoassay and direct inhibition test with anti-Ku sera from the autoimmune patients. The DNA-PK catalyzed phosphorylation of synthetic peptides corresponding to Myc and RB proteins in a DNA-dependent manner, indicating that DNA-PK may recognize a second core-sequence motif Pro-Ser/Thr- in addition to the putative consensus sequences of -Ser/Thr-Gln. The level of enzyme activity was significantly higher in DMSO-induced G0/G1-arrested Raji cells as well as in the cells after release from DMSO than in the log-phase cells.
Amino Acid Sequence↗
DNA-dependent protein kinase (Ku protein-p350 complex) assembles on double-stranded DNA.
The Ku protein is an autoantigen that consists of 70- and 80-kDa polypeptides. It associates with double-stranded DNA at free ends. In the present study, we examined the ability of anti-Ku antibodies to immunoprecipitate various structures from extracts of HeLa cells prepared at different salt concentrations. Under physiological conditions, these antibodies identified a complex containing the Ku protein and the 350-kDa component (p350) of DNA-dependent protein kinase (DNA-PK), which appeared to be closely associated on the DNA strand. In reconstitution experiments with cell extracts and biochemically purified components, the Ku protein-p350 complex formed only in the presence of double-stranded DNA. The reconstituted complex was catalytically active. Together with previous studies, these results indicate that the Ku protein interacts with DNA to create a binding site for p350 as the DNA-PK holoenzyme assembles.
Antigens, Nuclear↗
Clinical significance of antibodies to native or denatured 60-kd or 52-kd Ro/SS-A proteins in Sjögren's syndrome.
OBJECTIVE: To evaluate the clinical significance of antibodies to native or denatured (anti-n or anti-d) 60- or 52-kd Ro/SS-A proteins (60K or 52K) in Sjögren's syndrome (SS). METHODS: The presence of antibodies to denatured and native Ro/SS-A proteins was determined by immunoblotting and immunoprecipitation, respectively. Salivary gland dysfunction was evaluated by salivary function scintigraphy. RESULTS: The incidence of anti-d-60K without anti-d-52K was lower among patients with systemic lupus erythematosus with SS (SLE/SS) and among those with primary SS, compared with patients who had SLE without SS, whereas anti-d-52K without anti-d-60K was more common in SLE/SS patients and primary SS patients than in SLE patients without SS. All of the patients with anti-Ro/SS-A had anti-n-60K. Serologic abnormalities and salivary gland dysfunction were associated with anti-n-60K in SS, whereas Hashimoto's thyroiditis in SS was related to anti-d-60K. Anti-d-52K was not associated with any extraglandular or glandular symptoms in SS. CONCLUSION: The data indicate that anti-n-60K, which appears to recognize conformational epitopes, is associated with clinical features of SS characterized by glandular dysfunction.
Autoantibodies↗
[Detection of autoantibodies in sera from patients with rheumatoid arthritis].
Although Rheumatoid Arthritis (RA) is categorized in the systemic autoimmune diseases, specific autoantibodies in RA have been reported to be rare. We have investigated autoantibodies found in sera from patients with RA and examined their clinical significance. Immunoprecipitation techniques using 32P-labeled or 35S-labeled HeLa cell extracts and immunoblotting were utilized to detect autoantibodies in sera from 42 patients with RA and 58 patients with other connective tissue diseases as controls. Certain autoantibodies were detected in 33 of 42 patients (79%) with RA by any of the assay systems mentioned above. Anti-SSA/Ro, anti-SSB/La, anti-7-2RNP, and anti-Sm antibodies were found in 13 (29%), 3 (7%), 4 (10%), and 1 (2%) patients with RA, respectively. All 3 patients with anti-SSB/La and 9 with anti-SSA/Ro revealed Sjögren's syndrome besides RA. However, all 4 patients with anti-7-2RNP and one patient with anti-Sm showed no evidence of scleroderma nor SLE. Besides of these known autoantibodies, we have also detected 4 new antibodies which reacted with a 60kD protein in 15 (36%), 45kD in 10 (24%), 75kD in 8 (19%), 180kD in 4 patients (10%) with RA. These autoantibodies were not found in other connective tissue diseases except one of SLE for anti-60kD and one of dermatomyositis for anti-75kD, and therefore appeared to be specific for RA patients. Anti-45kD antibodies were associated with low prevalence of anti-nuclear antibodies, and anti-180kD antibodies were associated with lymphadenopathy and Sjögren's syndrome. Thus, it was demonstrated that patients with RA develop a variety of autoantibodies as well as those with other connective tissue diseases.
Arthritis, Rheumatoid↗
[A new autoantibody anti-Na which reacts with a cell cycle-dependent nuclear antigen].
By immunofluorescent techniques many autoantibodies have been detected in sera from patients with connective tissue diseases. A distinct antinuclear antibody reacting with a cellular component which showed a characteristic expression pattern is reported. The new antibody, termed anti-Na, stained approximately 20-30% of the HEp-2 cell with a variegated speckled pattern. In synchronized cell analysis, anti-Na showed fine speckles in G2/M phase cells, discrete speckles in dividing chromosomes, and specific cytoplasmic staining in anaphase and telophase cells. Although the preliminary study showed that 3% of SLE patients had anti-Na, the frequency of the anti-Na antibody in rheumatic diseases and their clinical significance remain to be clarified. Screening of a lambda gt11 cDNA expression library with anti-Na antibody yielded only one cDNA encoding a portion of this autoantigen. Deduced amino acid sequences of this cDNA showed a partial homology with myosin heavy chain of C. elegans, suggesting that the Na antigen is involved in contractibility related to myosin.
Amino Acid Sequence↗
[Study on combined of auranofin, salazosulfapyridine and methotrexate in rheumatoid arthritis].
Patients with rheumatoid arthritis who did not respond sufficiently to auranofin therapy were divided into three groups to be continued on auranofin monotherapy (1), to be on combination therapy of auranofin and salazosulfapyridine (2) and to be given methotrexate concomitantly with auranofin (3), and clinical responses were compared in a prospective manner. Patients on combination therapy either with salazosulfapyridine or with methotrexate demonstrated higher improvement than those on continued auranofin monotherapy. No unknown side effects associated with monotherapy of any of the three compounds were seen in any of the three groups. The study suggests usefulness of combination therapy either with methotrexate or with salazosulfapyridine for patients who failed to respond sufficiently to auranofin.
Adult↗
[Two cases of rheumatoid arthritis presenting autoimmune hepatic diseases].
We report on two cases of rheumatoid arthritis (RA) presenting autoimmune hepatic diseases. The first patient, who had been diagnosed as RA at the age of 63, was hospitalized in order to undergo surgery for total left knee replacement at the age of 69. She acquired acute serum hepatitis as a result of blood transfusion she received during the operation. Five years later, she visited our clinic suffering from polyarthritis. She was found to have hyper-alkaline phosphatase (ALP) and hyper rGTP, but no AMA. The second patient, a 60-year-old female whose onset of RA was at the age of 45, complained of general fatigue, and was admitted to the hospital because of persistent liver dysfunction. When corticosteroid was administered to these patients, ALP and rGTP levels in the first case, and AST and ALT levels in the second case were reduced to values in the normal range. ANA in the first case continued to register negative, but ANA in the second case became positive after the patient developed acute hepatitis. Both patients were found to have anti-p25 triplet liver/kidney microsome antibody. We discuss the clinical significance of this antibody.
Aged↗