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Biomedical subjects

M Akizuki

Publications and source records attributed to M Akizuki.

At least 19 recordsLinked to original sources
PubMed2001

Lack of association between the Met196Arg polymorphism in the TNFR2 gene and autoimmune diseases accompanied by vasculitis including SLE in Japanese.

A polymorphism in high-affinity receptor of TNF (TNFR2) gene, Met196Arg, was reported to be associated with systemic lupus erythematosus (SLE) in Japanese, whereas the association could not be found in Europeans at all and this represents an apparent discrepancy. The association, then, should be tested in other populations to clarify the possible involvement, if any, of the TNFR2 polymorphism in SLE or other related autoimmune diseases. The purposes of this study were to examine the TNFR2 polymorphism in Japanese patients with SLE and to investigate its association with other autoimmune diseases accompanied by vasculitis, mixed connective tissue disease, Buerger's disease, and Takayasu's arteritis. We found no association at all between the TNFR2 polymorphism and any autoimmune diseases including SLE in Japanese.

Amino Acid Substitution↗
PubMed2001

[A multicenter cross-sectional study on the Health Related Quality of Life of patients with rheumatoid arthritis using a revised Japanese version of the Arthritis Impact Measurement Scales Version 2 (AIMS 2), focusing on physical disability and its associative factors].

OBJECTIVE: A multicenter cross-sectional survey was conducted to study the current status of Health Related Quality of Life (HRQL) of Japanese patients with rheumatoid arthritis using a revised Japanese version of the AIMS 2, to investigate the association among the self-report physical disability scores and demographic, socioeconomic, and clinical variables in these patients. METHODS: A Japanese version of the AIMS 2 was administered to the randomly chosen 1614 patients with classical and definite rheumatoid arthritis attending arthritis clinics at eleven hospitals across the country. Self-report functional disability scores (FDSs) were calculated, by which patients were classified into five groups with graded levels of disability. Univariate correlations were examined between FDSs and the scores of the other four components of AIMS-HRQL, disease duration, age, medical costs, and physical and laboratory measures. Analysis of variance was performed to test for among level differences of these variables in each group of patients. Mean values and standard deviations of FDSs were calculated and analysis of variance was used to test for among level differences of the following factors: demographic, socio-economic, clinical measures, and treatment status. RESULTS: Among four scales composing the AIMS 2-HRQL, work disability scores were most strongly correlated with FDSs, followed by the scores of pain, affection and social interaction. The more severely disabled group proved to have weaker grip strength, higher joint count, longer disease duration, higher ESR and blood level of CRP, and lower level of Hb. Patients with more disabilities proved to be older, pay more medical costs, have longer duration of morning stiffness, and higher level of RF. Patients with more advanced Steinbrocker's functional class, doctor's global assessment, Steinbrocker's anatomical stage, higher daily dose of prednisolone intake, lower level of annual income and formal education, and patients taking more kinds of NSAIDs proved to be more severely disabled. Separate, single (never married, widowed), and divorced patients proved to be more severely disabled compared with married ones. Overall, females were more disabled than males. CONCLUSION: Physical disability is associated with the other important aspects of QOL, clinical signs and symptoms, and socio-economic conditions in RA patients. Prevention and management of physical disability should be seriously planned in consideration of the changes in these conditions in RA patients.

Arthritis, Rheumatoid↗
PubMed2000

Autoantibodies to DEK oncoprotein in human inflammatory disease.

OBJECTIVE: To evaluate the specificity of anti-DEK antibodies for juvenile rheumatoid arthritis (JRA). METHODS: Anti-DEK autoantibodies were measured by enzyme-linked immunosorbent assay (ELISA) using affinity-purified his6-DEK fusion protein. Sera from 639 subjects (417 patients with systemic autoimmune disease, 13 with sarcoidosis, 44 with pulmonary tuberculosis, 125 with uveitis, and 6 with scleritis, and 34 healthy control subjects) were screened. Reactivity was verified by immunoblotting and immunoprecipitation studies using baculovirus-expressed human DEK. RESULTS: Anti-DEK activity was found at the following frequencies: JRA 39.4% (n = 71), systemic lupus erythematosus (SLE) 25.1% (n = 216), sarcoidosis 46.2% (n = 13), rheumatoid arthritis 15.5% (n = 71), systemic sclerosis 36.0% (n = 22), polymyositis 6.2% (n = 16), and adult Still's disease 0% (n = 21). Autoantibodies also were detected in 9.1% of tuberculosis sera (n = 44), but were undetectable in sera from the 34 healthy controls. Western blot and immunoprecipitation assay results correlated well with the ELISA findings. In general, levels of anti-DEK autoantibodies were higher in SLE than in other patient subsets, including JRA. CONCLUSION: Anti-DEK autoantibodies are less specific for JRA than previously believed. They are produced in association with a variety of inflammatory conditions, many of which are associated with granuloma formation and/or predominant Thl cytokine production. Anti-DEK antibodies may be a marker for a subset of autoimmunity associated with interferon-gamma production rather than a particular disease subset.

Adolescent↗
PubMed2000

[Granulocytic sarcoma presenting as an epidural mass with spinal cord compression].

A 73-year-old man was admitted because of back pain and paralysis of the lower extremities. Magnetic resonance imaging of the spine at the Th4-6 level, obtained after gadolinium injection, demonstrated abnormal signal intensity within the Th5-6 vertebral bodies and an extradural soft-tissue mass on the right posterior side of the spinal canal, compressing the thecal sac. The patient underwent prompt decompression with laminectomy, but this was unsuccessful. A biopsy sample of the mass revealed the histological features of granulocytic sarcoma, including diffuse infiltration of numerous cells containing cytoplasmic granules and immunohistochemical positivity for myeloperoxidase. Two months later, a subcutaneous soft-tissue mass appeared at the anterior chest wall, and this was confirmed to be granulocytic sarcoma by microscopic examination. Both of these tumors were radiosensitive, but the patient died of septic shock. Granulocytic sarcoma usually occurs in association with leukemia or other myeloproliferative disorders. However, it is rarely found before leukemia becomes evident in the peripheral blood or bone marrow; only eight such instances have been reported previously.

Aged↗
PubMed1999

Mice homozygous for a truncated form of CREB-binding protein exhibit defects in hematopoiesis and vasculo-angiogenesis.

CREB-binding protein (CBP) and the closely related adenovirus E1A-associated 300-kD protein (p300) function as coactivators of transcription factors such as CREB, c-Fos, c-Jun, c-Myb, and several nuclear receptors. To study the roles of CBP in embryonic development, we generated CBP homozygous mutant mouse embryos that expressed a truncated form of CBP protein (1-1084 out of 2441 residues). The embryos died between embryonic days 9.5 (E9.5) and E10.5 and exhibited a defect in neural tube closure. They appeared pale and showed decreases in erythroid cells and colony-forming cells (CFCs) in the yolk sac, suggesting defects in primitive hematopoiesis. Immunohistochemistry with an anti-PECAM antibody showed a lack of vascular network formation. Organ culture of para-aortic splanchnopleural mesoderm (P-Sp) with stromal cells (OP9) showed an autonomous abnormality of putative endothelial precursors, which may induce the microenvironmental defect in hematopoiesis. In addition, these defects were partially rescued by the addition of VEGF to this culture. Our analyses demonstrate that CBP plays an essential role in hematopoiesis and vasculo-angiogenesis.

Animals↗
PubMed1999

Anti-KS: identification of autoantibodies to asparaginyl-transfer RNA synthetase associated with interstitial lung disease.

Autoantibodies to five of the aminoacyl-transfer RNA (tRNA) synthetases have been described, and each is associated with a syndrome of inflammatory myopathy with interstitial lung disease (ILD) and arthritis. Serum KS, from a patient with ILD and inflammatory arthritis without evidence of myositis, immunoprecipitated a tRNA that was distinct from that precipitated by any described anti-synthetase or other reported tRNA-related Abs, along with a protein of 65 kDa. KS serum and IgG fraction each showed significant (88%) inhibition of asparaginyl-tRNA synthetase (AsnRS) activity, but not of any of the other 19 aminoacyl-tRNA synthetase activities. Among 884 patients with connective tissue diseases tested, only two other sera were found to immunoprecipitate tRNAs and proteins of identical gel mobility. These two and KS showed identical immunodiffusion lines using HeLa cell extract. The new sera significantly inhibited AsnRS without significant effects on other synthetases tested. Both patients had ILD but neither had evidence of myositis. These data strongly suggest that these three sera have autoantibodies to AsnRS, representing a sixth anti-synthetase. Anti-KS was more closely associated with ILD than with myositis. Further study of this Abs might prove useful in dissecting the stimuli responsible for the genesis of anti-synthetase autoantibodies.

Adult↗
PubMed1999

Extrahepatic biliary atresia associated with trisomy 18.

A case of extrahepatic biliary atresia (EBA) associated with trisomy 18 is presented. A 1-month-old boy was suspected to have Alagille syndrome with obstructive jaundice, a systolic heart murmur, growth retardation, and a small, pointed chin. However, surgery and chromosomal analysis revealed EBA associated with trisomy 18. Chromosomal examination must be performed in patients with jaundice and congenital anomalies. It is possible that EBA in trisomy 18 syndrome is due to a chromosomal disorder.

Bile Ducts, Extrahepatic↗
PubMed1999

Exchangeable gene trap using the Cre/mutated lox system.

The gene trap technique is a powerful approach for characterizing and mutating genes involved in mouse development. However, one shortcoming of gene trapping is the relative inability to induce subtle mutations. This problem can be overcome by introducing a knock-in system into the gene trap strategy. Here, we have constructed a new gene trap vector, pU-Hachi, employing the Cre-mutated lox system (Araki et al., 1997), in which a pair of mutant lox, lox71 and lox66, was used to promote targeted integrative reaction by Cre recombinase. The pU-Hachi carries splicing acceptor (SA)-lox71-internal ribosomal entry site (IRES)-beta-geo-pA-loxP-pA-pUC. By using this vector, we can carry out random insertional mutagenesis as the first step, and then we can replace the beta-geo gene with any gene of interest through Cre-mediated integration. We have isolated 109 trap clones electroporated with pU-Hachi, and analyzed their integration patterns by Southern blotting to select those carrying a single copy of the trap vector. By use of some of these clones, we have succeeded in exchanging the reporter gene at high efficiency, ranging between 20-80%. This integration system is also quite useful for plasmid rescue to recover flanking genomic sequences, because a plasmid vector sequence can be introduced even when the pUC sequence of the trap vector is lost through integration into the genome. Thus, this method, termed exchangeable gene trapping, has many advantages as the trapped clones can be utilized to express genes with any type of mutation.

Animals↗
PubMed1998

Gallbladder contraction in biliary atresia: a pitfall of ultrasound diagnosis.

In 3 (9 %) of 34 children with biliary atresia, US revealed gallbladder contraction following an oral feed, given on admission, but not with subsequent feeds. Surgery revealed a Kasai type IIIa biliary atresia with a patent communication between the gallbladder and duodenum. We propose that the bile ducts may initially have been patent, but then gradually became obliterated secondary to inflammation. These cases may explain the development of one type of biliary atresia.

Biliary Atresia↗
PubMed1998

Transiliac catheterization of the inferior vena cava for long-term venous access in children.

In infants and children requiring prolonged, multiple central venous (CV) catheterizations, the superior (SVC) and inferior vena cava may become thrombosed or stenotic, making CV access a difficult problem. Use of the iliac vein may be an acceptable alternative. We report a patient with thrombosis of the SVC in whom the external iliac vein was accessed through a retroperitoneal approach for placement of an implantable port. This technique is easy to perform, and there are no special materials or patient positioning required.

Catheterization, Central Venous↗
PubMed1998

[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↗
PubMed1998

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↗
PubMed1997

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↗
PubMed1997

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↗