Search PubMed⌕ Search

Biomedical subjects

T Mimori

Publications and source records attributed to T Mimori.

At least 55 records · Page 3Linked to original sources

A novel antibody directed against a three-dimensional configuration of a 95-kDa protein in patients with autoimmune hepatic diseases.

Sera from patients with primary biliary cirrhosis recognize various cellular components, such as mitochondria, centromere, nuclear envelope, and multiple nuclear dot antigens. There also appears to be a novel antibody reacting with a particular protein in these sera. The presence of this antibody was investigated by double immunodiffusion using rat liver cytoplasmic antigens, by immunoprecipitation of [35S]-methionine labelled HeLa cell extracts, and by immunoblot using disrupted HeLa cell extracts. Test sera were obtained from 491 patients with various liver diseases. Nine of the 491 sera were found to react with a 95-kDa protein as determined by immunoprecipitation of [35S]-methionine labelled HeLa cell extracts and by double immunodiffusion using a rat liver microsomal preparation. However, these same nine sera showed no reaction in the immunoblot assay. On the basis of its molecular mass and its presence in the cytoplasmic fraction, this antigen was named p95 C. This anti-p95 C antibody was detected in six of 50 (12%) sera from patients with primary biliary cirrhosis, and in three of 31 (9.7%) sera from patients with autoimmune hepatitis, but not in any of the remaining 410 sera obtained from patients with other hepatic diseases. It is concluded that anti-p95 C antibody reacts primarily with the native form of the 95-kDa protein, and represents another possible analyte for diagnosing autoimmune liver diseases.

Aged↗

T cell receptor clonotypes in skin lesions from patients with systemic lupus erythematosus.

Systemic lupus erythematosus is an autoimmune disease characterized by the presence of autoantibodies and by lymphocytic infiltration into lesions at several sites such as skin, kidney, and other organs. Immunohistologic studies have clarified that the majority of lymphocytes in the skin are CD4+ alphabeta T cells. In the present work, to clarify the pathologic role of T cells in the skin of systemic lupus erythematosus patients, we analyzed T cell receptor (TCR) clonotypes of T cells infiltrating into skin lesions. TCR Vbeta gene transcripts from T cells from discoid lesions of the skin and peripheral blood lymphocytes of four systemic lupus erythematosus patients were amplified by reverse transcriptase polymerase chain reaction. Southern blot analysis of polymerase chain reaction product demonstrated the heterogeneous TCR Vbeta repertoire of T cells in the skin of systemic lupus erythematosus. Single-strand conformation polymorphism analysis showed several distinct bands for smears of most TCR Vbeta genes from T cells infiltrating the skin, whereas smears with few bands were found for all TCR Vbeta genes from peripheral blood lymphocytes of the same patients. The number of bands encoding each TCR Vbeta gene from the skin was significantly higher compared with peripheral blood lymphocytes. Sequencing analysis showed a Leucine-X-Glycine amino acid motif at position 96-98 in the CDR3 region at the frequency of 23-24% in skin-accumulated T cells from two patients, whereas the frequency of this motif in peripheral T cells was only 0-3%, indicating limited T cell epitopes. In conclusion, T cells infiltrating into the skin of systemic lupus erythematosus patients might recognize restricted T cell epitopes on autoantigens and trigger the autoimmune reaction in skin lesions.

Amino Acid Sequence↗

Ku antigen binds to Alu family DNA.

The GC-rich segment containing GGAGGC (Alu core) is conserved within the RNA polymerase III (pol III) promoters of Alu family sequences. We have shown that the GGAGGC motif functions as a modulator of DNA replication as well as of transcription, and identified the proteins binding to the motif in human HeLa cells. In this study, the Alu core binding proteins were partially purified from human Raji cells by using an Alu core DNA affinity column. Both the proteins thus purified were implied to be subunits of Ku antigen based on the following criteria: The molecular weights of the proteins estimated on gel electrophoreses were 70 and 85 kDa, respectively, under denaturing conditions, while under non-denaturing conditions only one band was observed for the same sample at 150 kDa, probably representing hetero-dimer formed between the 70 and 85 kDa proteins. The sizes and the hetero-dimer formation are reminiscent of the 70 and 80 kDa subunits of Ku antigen (Ku-p70 and Ku-p80). Moreover, the purified proteins were immunoreactive with anti-Ku antibodies, and the specific DNA-protein complex on the Alu core element was cancelled by the anti-Ku antibodies. The nucleoprotein complex showed the same clipping patterns as those of the complex between the Alu core element and an authentically purified Ku antigen after proteolytic cleavage with trypsin and chymotrypsin.

Antigens, Nuclear↗

[Detection of isotype-specific autoantibodies to calpastatin in sera from patients with rheumatic diseases using heat-treated HeLa cell extract as an antigen source for immunoblotting].

To detect immunoglobulin isotype-specific autoantibodies to native human calpastatin in patients with rheumatic diseases, we performed immunoblot analysis using the heated HeLa cell extracts to enrich heat-resistant calpastatin. The calpastatin molecule that was apparently migrated to 110 kD by SDS-PAGE was confirmed to react with monoclonal anti-human calpastatin antibody in immunoblotting. IgG antibodies to calpastatin were detected in 22 of 48 sera (46%) from patients with RA, whereas only 20% (5/25), 11% (2/19) and 13% (2/15) of sera from SLE, SSc and PM/DM had IgG anti-calpastatin antibodies, respectively. IgM antibodies were also found in 40% (19/48) of RA and 12% (3/25) of SLE patients but not detected in sera from patients with other rheumatic diseases. IgA antibodies were found in only one RA and one SLE serum. In RA, 7 of 48 sera (15%) had IgM antibodies alone, but all SLE sera with IgM antibodies had IgG antibodies. Thus, anti-calpastatin autoantibodies were detected by using the native human calpastatin. Although these autoantibodies were found in patients with various rheumatic diseases, they were present in RA patients at the highest frequency. In particular, the presence of IgM antibodies appeared to be more specific in RA patients.

Arthritis, Rheumatoid↗

[A case of systemic lupus erythematosus associated with spinal epidural hematoma].

A 47 year-old Japanese female who showed transverse myelopathy (TM) due to spinal epidural hematoma diagnosed by MRI in the course of systemic lupus erythematosus (SLE) was reported. She was admitted to Keio University Hospital due to paraplegia, anesthesia of lower extremity, urinary disturbance. Neurological examination revealed transverse disturbance of Th 10. Lumbar spinal cord MRI showed irregular mass that located at epidural region of 9th-11th thoracic vertebrae. When the laminectomy of 9th-11th thoracic vertebrae was performed, hematoma (4.5 cm x 1.5 cm in size) was confirmed and removed completely. Post operative condition was stable and symptoms had been improving gradually. It has been reported that TM associated with SLE was closely related to myelitis. In this case, epidural hematoma was a major cause of TM and MRI was very useful for her diagnosis and treatment. This is the rare case of SLE associated with spinal epidural hematoma and was thought as a important case to consider the cause of neurological complication of SLE.

Female↗

[Analysis of autoantigens and clinical significance of antinuclear antibodies].

A highly sensitive RNA-immunoprecipitation assay (Lerner-Steitz assay) is a unique and useful method of identifying autoantibodies to RNA-associated antigens. In this study, we identified novel autoantibodies to tRNAs using RNA-immunoprecipitation assay. In screening of 1472 sera by RNA-immunoprecipitation using HeLa cell extracts as an antigen source, 41 sera were found to immunoprecipitate tRNAs. Fifteen of these 41 sera also immunoprecipitated deproteinized tRNAs, indicating that these 15 sera contained anti-tRNA antibodies. Three sera immunoprecipitated naked tRNA from E. coli. When in vitro transcripts from cDNAs encoding E. coli tRNAs and their synthesized mutants were used as antigens, it was demonstrated that the representative serum recognized the conformational epitope of the "L"-shape structure which was conserved in all tRNAs of all species. This finding suggests the role of bacterial infection in the development of autoantibodies and autoimmune diseases. Two of 15 sera containing anti-tRNA antibodies were identified as anti-PL-12 (alanyl-tRNA synthetase) antibodies. Eleven of the remaining 13 patients were diagnosed as either SLE, Sjögren's syndrome or their overlap. In addition, fever, Raynaud's phenomenon, polyarthritis, leukocytopenia and characteristic annular erythema were frequently found in these patients. Novel autoantibodies to tRNAs appeared to be associated with common clinical features but were distinct from previously described anti-aminoacyl-tRNA synthetases.

Alanine-tRNA Ligase↗

[Two cases of polymyositis associated with interstitial pneumonia with anti-OJ (isoleucyl tRNA synthetase) antibodies].

We present two cases of polymyositis (PM) associated with interstitial pneumonia (IP) whose sera contain autoantibodies to OJ (isoleucyl tRNA synthetase). The first patient is a 51 year-old female who was diagnosed as rheumatoid arthritis (RA) and treated with gold and corticosteroid at another hospital. She was admitted to Keio University Hospital due to worsening of dyspnea on exertion and polyarthritis. Laboratory findings revealed elevation of serum CK and LDH. A diagnosis of PM was made based on the myogenic pattern of EMG and pathological feature by muscle biopsy. Chest radiography and CT showed interstitial fibrosis. Because of clinical deterioration, the dose of corticosteroid was increased (prednisolone 50 mg/day) and her symptom was stabilized. The second patient, a 62 year-old male, was admitted to Kawasaki Municipal Hospital because of dyspnea on exertion, polyarthritis, and fever. He was diagnosed as PM associated with IP on the basis of his clinical and laboratory findings, and chest radiography. He was treated with methylprednisolone pulse therapy (800 mg/day for three days) and his symptoms were improved. Both patients were found to have autoantibodies to OJ. Autoantibodies to aminoacyl tRNA synthetase have been described to be associated with myositis and/or IP. In North American, it was reported that all patients with anti-OJ had either myositis or IP or both. This suggests that anti-OJ was commonly associated with the anti-synthetase syndrome observed with other anti-synthetases. This is the first report of Japanese patients with anti-OJ antibody. The clinical features of these patients were likely to be similar to those observed in North American patients. However, further studies are necessary to clarify the precise clinical significance of this antibody.

Autoantibodies↗

Chronic arthritis and carpo:metacarpal ratio in Japanese patients with adult Still's disease.

OBJECTIVE: To characterize Japanese patients having adult Still's disease (ASD) with chronic arthritis (> 6 months) and to examine the association of chronic arthritis with carpo:metacarpal ratio (CMC ratio), an index of radiographic progression in rheumatoid arthritis (RA). METHODS: Twenty-seven patients with ASD (16 women and 11 men, mean age at disease onset 27.7 years) were classified into 2 groups: patients with (chronic articular ASD, 16 patients, 59%) or without (systemic ASD, 11 patients, 41%) chronic arthritis. Clinical and laboratory findings were compared between both groups. CMC ratio was calculated on serial hand radiographs in patients with chronic articular ASD. RESULTS: In our series, serositis was rarely observed in chronic articular ASD. Peripheral arthritis (including transient arthritis), such as metacarpophalangeal, proximal interphalangeal, or ankle joint, was more frequently observed in chronic articular ASD than in systemic ASD (p < 0.05). Wrist arthritis was frequently observed also in systemic ASD; however, joint space narrowing of carpometacarpal or intercarpal joints was recognized only in chronic articular ASD (44%). CMC ratio at the last observation in 14 patients with chronic articular ASD was significantly decreased (0.526 +/- 0.039) compared to that at disease onset (0.553 +/- 0.034) (p < 0.05), while no decrease was observed in 4 with systemic ASD (0.565 +/- 0.062 at disease onset, 0.563 +/- 0.043 at the last observation). CONCLUSION: It is suggested that chronic articular ASD has certain characteristics. CMC ratio may be a quantitative index for assessment of radiographic changes of carpal joints, not only in RA but also in chronic articular ASD.

Arthritis↗

Characterization and evolution of a gene encoding a Trimeresurus flavoviridis serum protein that inhibits basic phospholipase A2 isozymes in the snake's venom.

The proteins that bind phospholipase A2 (PLA2) isozymes of Trimeresurus flavoviridis (habu snake, crotalinae) venom were fractionated from sera on four columns, each conjugated with one of four PLA2 isozymes. Five proteins, termed PLA2 inhibitors (PLI) I-V, were obtained as the binding components. The combinations of the binding components differed depending on the PLA2 isozymes. PLI-IV and PLI-V correspond to PLI-A and PLI-B, respectively, which were known to bind to a major [Asp49]PLA2, PLA2, and contained a segment similar to the carbohydrate-recognition domain of C-type lectins. PLI-I, which is a major component of inhibitory proteins against three basic PLA2 isozymes, PLA-B (a basic [Asp49]PLA2) and basic proteins I and II (both [Lys49]PLA2s), has been isolated, and its partial amino acid sequence has been determined. A cDNA encoding PLI-I was isolated from a T. flavoviridis liver cDNA library and sequenced. PLI-I cDNA encoded 200 amino acid residues, including a signal peptide of 19 amino acid residues. One sugar chain was predicted to occur at position 157. A gene coding for PLI-I was isolated. It is 9.6-kb long and consists of five exons and four introns. Comparison of the exon-intron structure of the PLI-I gene with those of genes encoding urokinase-type-plasminogen-activator receptor (uPAR), Ly-6, CD59 and neurotoxins showed that they have characteristic unit encoding approximately 90 amino acid residues, which is divided over two exons. This strongly suggests that the PLI-I gene belongs to the uPAR, Ly-6, CD59 and neurotoxin gene family. There are two types of structurally different inhibitors against PLA2 isozymes in T. flavoviridis serum with different evolutionary origins.

Amino Acid Sequence↗

Systemic lupus erythmatosus associated with autoimmune hepatitis two cases with novel autoantibodies to transfer RNA-related antigens.

Two cases of systemic lupus erythematosus (SLE) with autoimmune hepatitis are reported. Both patients had a mild form of SLE without central nervous system or renal involvement and showed a rapid response to corticosteroid therapy. Neither of them had antibodies to mitochondria, smooth muscle, and liver/kidney microsome-1 related to autoimmune hepatitis. Instead, novel autoantibodies which react with transfer RNA-related antigen were detected. These autoantibodies could be a useful marker for classification of SLE associated with autoimmune hepatitis.

Adult↗

Re-expression of functional P-selectin molecules on the endothelial cell surface by repeated stimulation with thrombin.

P-selectin (GMP-140, PADGEM, CD62P) is a cell adhesion receptor which is believed to play an important role in inflammatory diseases by supporting leucocyte rolling. P-selectin is located on the granule membrane of Weibel-Palade bodies in resting endothelial cells and is expressed on the cell surface during cellular activation with various stimulators such as thrombin. Thereafter, P-selectin is internalized and sorted to the Golgi region and Weibel-Palade bodies again. However, whether P-selectin is re-expressed upon subsequent cellular stimulation has, to date, been unclear. To address this question, we measured the cellular content and surface expression of P-selectin, using indirect immunofluorescence and confocal laser cytometry. Surface expression of P-selectin reached a maximum < 2 min after thrombin stimulation and declined to basal levels after 180 min. Rechallenge with thrombin induced rapid surface re-expression of P-selectin, which was independent of de novo protein synthesis, since cycloheximide did not inhibit re-expression. Moreover, re-expressed P-selectin supported the adherence of HL60 promyelocytic cells. These results clearly demonstrated that functional P-selectin molecule was recycled after repeated stimulation with thrombin, raising the possibility that P-selectin is involved in chronic inflammation.

Endothelium, Vascular↗

Methotrexate treatment in patients with adult onset Still's disease--retrospective study of 13 Japanese cases.

OBJECTIVE: To evaluate methotrexate treatment in patients with active adult onset Still's disease (AOSD). METHODS: Methotrexate was initially given as a single weekly oral dose of 5 mg and adjusted individually afterwards in 13 patients with active AOSD. Symptoms and laboratory findings were investigated. RESULTS: Signs of AOSD activity disappeared (remission) in eight patients between 3 and 16 weeks after starting methotrexate. In these patients, significant improvements in C reactive protein, erythrocyte sedimentation rate, white blood count, and serum ferritin were observed at 8, 12, 14, and 16 weeks after starting methotrexate, respectively. In six of these eight patients, steroids or non-steroidal anti-inflammatory drugs could be reduced or discontinued. In four patients methotrexate was not effective despite 12 or 16 weeks of treatment, and one patient discontinued treatment after 2 weeks because of severe nausea. Five patients suffered from adverse reactions, including acute interstitial pneumonia (one patient) and liver toxicity (two patients). Five out of eight patients successfully treated with methotrexate were HLA-DR4 positive (four homozygotes), and all the unsuccessfully treated patients were DR2 positive. CONCLUSIONS: Methotrexate is useful for controlling disease activity in AOSD, not only for refractory patients but also for patients who have never taken steroids or for those with steroid associated toxicity. However, serious adverse reactions can occur, as with rheumatoid arthritis. It is important to determine the critical factors, such as the immunogenetic background, that are associated with response to methotrexate treatment.

Adult↗

Mixed-cryoglobulinemia associated with cutaneous vasculitis and pulmonary symptoms.

A 45-year-old Japanese man with Sjögren's syndrome developed recurrent skin ulcers, palpable purpura, and dyspnea. Serum mixed-type cryoglobulin level was elevated. A biopsy of his skin lesion showed the characteristic leukocytoclastic vasculitis of mixed-type cryoglobulinemia. Dyspnea, skin ulcers, and purpura resolved along with a reduction in the serum cryoglobulin level after prednisolone administration. This patient demonstrated cryoglobulinemia-associated vasculitis, as well as possible cryoglobulinemia-associated pulmonary symptoms.

Cryoglobulinemia↗

[An adult case of dermatomyositis complicated with cecum perforation and panniculitis].

The case of dermatomyositis complicated with cecum perforation and panniculitis occurred in a 62-year-old woman was reported. She was admitted to Keio University Hospital with a history of proximal muscular weakness, and dysphagia. Physical examination showed erythema over the face and shoulder. Serum level of muscle enzymes was remarkably increased. The diagnosis of dermatomyositis was made based on proximal muscular weakness, elevated serum level of muscle enzymes and myogenic change of electromyocardiogram. The treatment with 60 mg/day of prednisolone was started, and was a good response. However, 7 months later the disease became active again when the amount of prednisolone was reduced to 13 mg/day. Subsequently she complained of abdominal pain on the right lower quadrant. The surgical findings included peritonitis due to the perforation of the cecum and multiple ulcers of the cecum. After operation, azathioprine was added. Four years and 9 months later, she noticed skin erythema with ulceration and subcutaneous nodule. Skin biopsy indicated the findings of the panniculitis with membrano-cystic lesion. It was thought that both cecum perforation and panniculitis were caused by angiopathy which was often seen in childhood dermatomyositis.

Cecal Diseases↗

[Toxicity of low-dose methotrexate in rheumatoid arthritis--clinical characteristics in patients with MTX-induced pancytopenia and interstitial pneumonitis].

Pancytopenia and interstitial pneumonitis are one of the most serious and unpredictable adverse effects of low dose, pulse methotrexate (MTX) in treating rheumatoid arthritis (RA). It is important to investigate the historical, clinical or immunologic features associated with the development of such toxicity, in order to use MTX more appropriately. Two hundred eighty four patients (female 230 male 54) with rheumatoid arthritis had been treated with pulse weekly oral MTX with a mean follow-up of 33.2 months. Adverse effects which required the discontinuation of MTX occurred in 47 patients (16.5%). Gastrointestinal toxicity occurred most frequently (14 patients) and liver dysfunction occurred in 9 patients. Four patients (1.4%) developed pancytopenia, and six patients (2.1%) developed interstitial pneumonitis. All patients who developed pancytopenia were old female with long history of active, deforming rheumatoid arthritis, The cumulative dose of MTX ranged from 15 mg to 760 mg at the time pancytopenia developed. Impaired renal function, hypoalbuminemia, and multiple medication were observed, and antinuclear antibodies were positive in most patients. It should be noted that severe stomatitis preceded or accompanied with pancytopenia in all patients. Blood counts returned to the normal level in 7 to 14 days. All patients who developed interstitial pneumonitis were old female. The cumulative dose ranged from 65 mg to 580 mg. Pre-existance of lung diseases, history of adverse effects of other DMARDs, the presence of Raynaud's phenomenon, and antinuclear antibodies appeared to be risk factors for interstitial pneumonitis. All patients recovered with high dose of corticosteroid and mechanical ventilation. Such clinical characteristics that are associated with MTX-induced pancytopenia or interstitial pneumonitis should be reminded in the treatment of rheumatoid arthritis with MTX.

Aged↗