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Biomedical subjects

M Akizuki

Publications and source records attributed to M Akizuki.

At least 37 records · Page 2Linked to original sources
PubMed1997

[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↗
PubMed1997

[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↗
PubMed1997

[A new approach to assessing rheumatoid arthritis (RA) disease activity using the American College of Rheumatology core set of disease activity measures for RA trials--a multi-center study].

To characterize the American College of Rheumatology core set of disease activity measures for rheumatoid arthritis (RA) clinical trials (ACR core set measures) and the ACR definition of improvement of RA (ACR improvement definition), we studied 42 Japanese patients with active RA who were treated with DMARDs including mizoribine. Each patient's disease activity was assessed at the time of enrollment to the study and after 24 weeks using the ACR core set measures as well as the physical global assessment through the conventional measures. Twenty-five (60%) patients were discerned as showing improved by physicians through the conventional measures. This decision appeared to be based on improvement in Lansbury activity index (LAI) and C-reactive protein (CRP) value. Twelve of the 25 "improved" patients satisfied the ACR improvement definition. The 12 patients showed significant improvement in "outcome" measures including patients assessments of pain, disease activity, and physical function, compared to the 30 patients not satisfying the ACR definition. However, no significant differences were observed between these two groups in "process" measures including LAI, tender joint count, swallen joint count, or CRP value. In conclusion, the ACR core set measures including both process and outcome measures have potential to reflect clinical important changes on "real life" of patients with RA.

Activities of Daily Living↗
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↗
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

Late development of anti-La/SS-B antibodies in a patient with Sjogren's syndrome and high titer anti-Ro/SS-A antibodies.

The frequent coexistence of anti-Ro and anti-La autoantibodies is well described, however, there is little evidence of sequential development of these two autoantibodies. We report a case of typical Sjogren's syndrome with high titer anti-Ro antibodies, who subsequently developed anti-La antibodies later in the course. This case suggests that the anti-La antibodies may actually follow the anti-Ro antibodies in some cases as hypothesized in the concept of linked set of autoantibodies, analogous to development of anti-Sm in certain anti-nRNP antibody positive SLE patients and animal models.

Antibodies, Antinuclear↗
PubMed1996

Restricted heterogeneity and changing spectrotypes in autoantibodies to La/SS-B.

Isoelectric focusing (IEF) spectrotype of specific immunoglobulins has been studied as a marker for B-cell clonality. In the present study, the spectrotype of anti-La antibodies in human autoimmune sera were analyzed by newly developed IEF sandwich assay in which focused total immunoglobulin on filter papers are incubated with crude antigen followed by horse-radish peroxidase-labeled anti-La antibodies. The anti-La spectrotypes contained oligoclonal bands, the positions and patterns of which are different in each patient, suggesting the preferential expansion of limited numbers of anti-La producing B-cell clones unique to individual patients. Furthermore, the bands on anti-La spectrotype in sequentially obtained sera changed continuously, suggesting alteration in the expanding anti-La producing clones. These may reflect affinity maturation and/or diversification of the B-cell epitopes involving somatic mutation.

Antibodies, Antinuclear↗
PubMed1996

[Pneumonia caused by varicella-zoster virus in a patient with rheumatoid arthritis].

A 56-year-old woman suffering from rheumatoid arthritis, was admitted to our hospital for evaluation of fever and dyspnea. A month before admission, she had been given a diagnosis of herpes zoster and was treated with an antiviral agent. However, a perineal eruption persisted. A chest X-ray film and a chest CT scan showed many diffuse nodular shadows in both lung fields. With conservative treatment, the shadows regressed along with the skin eruption and other symptoms. Pneumonia caused by varicella-zoster virus was diagnosed from the clinical course, chest roentgenographic and CT scan findings, and serological data. The risk of mortality in varicella-zoster pneumonia is high in adults, especially in immunosuppressed patients. Early diagnosis and effective treatment are, therefore, essential in the management of this disease. Though varicella-zoster pneumonia is rare, chest roentgenographic and CT scan findings are characteristic and suggestive. This case may serve as a reminder of the features of varicella-zoster pneumonia: many nodular shadows on the chest X-ray film and CT scan.

Aged↗
PubMed1996

[Prospective clinical study of the combination therapy of auranofin and methotrexate for rheumatoid arthritis--a multi-center study].

In a study to evaluate the usefulness of DMARDs combination therapy for RA, AF and MTX were concurrently given to RA patients who had responded poorly to over three months of monotherapy of either AF or MTX. The study was composed of two stages. In the first stage, patients were concurrently given AF and MTX for six months in order to evaluate the efficacy of combination therapy. In the second stage, patients who had responded to the earlier combination therapy were again put on monotherapy of the additive DMARD. Safety evaluation was conducted with 126 patients, and both efficacy and utility were evaluated in 100 patients. Lansbury index for RA significantly improved in both groups of patients starting with the AF and followed by the MTX combination (Group I) and those who started with MTX alone followed by the AF combination (Group II). The ratio of patients who achieved slight improvement or better in the overall improvement rating was significantly higher in Group I at 74.6%, vs. 51.1% in Group II patients. Ten patients (16.9%) and 2 patients (4.9%) were switched to their additive DMARD monotherapy of MTX and AF respectively, having responded to the combination therapy in stage I with slight improvement or a better rating. Adverse events were observed in 44 patients (34.9%), but the combination therapy neither increased the incidence of adverse events nor caused new adverse events. Combination therapy of AF and MTX appeared to be useful both in terms of efficacy and safety for patients who have experienced the dwindling effect of monotherapy.

Adult↗
PubMed1996

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↗
PubMed1996

[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↗
PubMed1995

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↗
PubMed1995

Malposition of a totally implantable venous access catheter in the azygous vein: report of a case.

We report herein the case of a 2-year-old girl with short bowel syndrome who developed chest pain 2 weeks after a totally implantable central venous access catheter had been surgically placed to facilitate total parenteral nutrition. A lateral chest X-ray and contrast flow study subsequently revealed that the catheter tip had been inserted into the azygous vein. Although this complication is very rare, it may be encountered more commonly with the increasing use of this type of venous access. Thus, we believe that a lateral chest X-ray should be routinely performed on all patients following catheter insertion to check for possible malposition of the tip in the azygous vein.

Catheters, Indwelling↗
PubMed1995

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↗
PubMed1995

Massive pericardial effusion in scleroderma: a review of five cases.

Medical records of five patients with scleroderma (SSc), each of whom had pericardial effusion with an estimated volume of more than 200 ml, were reviewed to study the clinical and immunological significance of massive pericardial effusion in SSc. Diffuse SSc (4/5), with a wide area of pigmentation (4/5), flexion contracture (4/5), oesophageal hypomotility (5/5), pulmonary fibrosis (4/5) and autoantibodies to topoisomerase I (3/5) were the common features in this group. High protein, lactate dehydrogenase and low white blood cell count were the characteristics of pericardial fluid. None of the patients had signs of acute pericarditis. Four of the five cases died within 9 months of the diagnosis of pericarditis; two with renal failure, one with cardiac tamponade and another with sudden death. The pericarditis in diffuse SSc, especially in cases with anti-topoisomerase I, may be characterized by a chronic form of pericarditis with poor prognosis, often complicated by renal failure.

Adult↗