Publications (74)242.32 Total impact
-
Article: Association of 5'-untranslated region of the Fibrillin-1 gene with Japanese scleroderma.
[show abstract] [hide abstract]
ABSTRACT: Excessive production of extracellular matrix (ECM) constituents is a hallmark scleroderma or systemic sclerosis (SSc). Fibrillin-1, a major component of microfibrils in the ECM, may play a role in the pathogenesis of SSc. The TSK1 mouse model of SSc bears an in-frame duplication of the Fibrillin-1 gene (FBN1) which results in a larger than normal protein that is more susceptible to proteolysis. Metabolic labeling studies of Fibrillin-1 in human SSc dermal fibroblasts demonstrated that while normal amounts of Fibrillin-1 are synthesized, the protein itself appears to be unstable. Moreover, autoantibodies specific for Fibrillin-1 have been demonstrated in serum from SSc patients and TSK1 mice. In particular, a high frequency of anti-Fibrillin-1 was observed in Japanese patients with diffuse and limited scleroderma or CREST (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia) syndrome. Genetic studies in a Native American population with high prevalence of using microsatellite marker showed strong association between FBN1 haplotypes and SSc. Subsequently, studies of FBN1 single nucleotide polymorphisms (SNPs) demonstrated that certain FBN1 haplotypes were associated with SSc in both Native American and Japanese patients with limited scleroderma. Thus, FBN1 was sequenced in 22 Japanese SSc patients to ascertain the presence of any relevant mutations or SNPs. Sequence analysis revealed eight coding and 14 non-coding SNPs and other polymorphisms. Among them, a CT insertion in the 5'-untranslated region of exon A had a significant negative association with disease.Gene 10/2002; 297(1-2):61-7. · 2.34 Impact Factor -
Article: CD56 positive intestinal T-cell lymphoma: treatment with high dose chemotherapy and autologous peripheral blood stem cell transplantation.
[show abstract] [hide abstract]
ABSTRACT: A 63-year-old man presented with a perforation of the small intestine. A diagnosis of intestinal T-cell lymphoma (ITCL) was made from CD (cluster differentiation) 3 positivity and a rearrangement of T-cell receptor genes. The tumor also expressed CD56, which suggests it belongs to a rare subtype derived from activated cytotoxic intraepithelial T lymphocytes. Although the prognosis of ITCL has been considered to be very poor irrespective of CD56 positivity, complete remission was achieved in this case by high dose chemotherapy followed by autologous peripheral blood stem cell transplantation (auto-PBSCT) even after relapse. Auto-PBSCT in the earlier stage of the disease might improve the prognosis.Internal Medicine 10/2002; 41(9):734-7. · 0.94 Impact Factor -
Article: Chemically modified ribozyme targeting TNF-alpha mRNA regulates TNF-alpha and IL-6 synthesis in synovial fibroblasts of patients with rheumatoid arthritis.
[show abstract] [hide abstract]
ABSTRACT: Rheumatoid arthritis (RA) is chronic polyarthritis in which a variety of inflammatory cytokines play a role. Since tumor necrosis factor-alpha (TNF-alpha) is one of the most important cytokines in the pathogenesis of RA, we evaluated the feasibility of ribozymes as a therapeutic agent to control the inflammatory process of RA synovium. A hammerhead ribozyme against TNF-alpha was chemically modified to increase nuclease resistance and added to RA fibroblastlike cell cultures without using a delivery system. The cellular uptake of fluorescent-labeled ribozyme into synovial cells was found to last at least 48 hr by confocal laser scanning microscopy. The ribozyme targeting TNF-alpha gene inhibited both the expression of TNF-alpha mRNA and the secretion of TNF-alpha and IL-6. The cytotoxic effect by the ribozyme on synovial cells was negligible when determined by an alamar blue assay. Chemically modified ribozymes designed to suppress the TNF-alpha gene may be potential as a therapeutic agent for rheumatoid arthritis.Journal of Clinical Immunology 08/2002; 22(4):228-36. · 3.08 Impact Factor -
Article: Regulation of tumor necrosis factor alpha promoter by human parvovirus B19 NS1 through activation of AP-1 and AP-2.
[show abstract] [hide abstract]
ABSTRACT: Human parvovirus B19 frequently causes acute and chronic arthritis in adults. The molecular mechanism of B19 arthritis, however, remains poorly understood. We previously showed that the transmission of B19 from rheumatoid synoviocytes to monocytic cells is associated with enhanced secretion of tumor necrosis factor alpha (TNF-alpha), which triggers inflammation, and interleukin-6. To determine the role of B19 in the production of TNF-alpha, we focused on the function of its nonstructural protein, NS1, and established monocytic U937 lines transduced with the NS1 gene under the control of an inducible promoter. Production of TNF-alpha mRNA and protein was elevated in a manner associated with NS1 expression. Reporter assays revealed that AP-1 and AP-2 motifs on the TNF-alpha promoter were responsible for NS1-mediated up-regulation. Electrophoretic mobility shift assay showed specific binding of nuclear proteins from NS1 gene-transduced cells with the AP-1 or AP-2 probe. Antibodies against transcription factors AP-1 and AP-2 and anti-NS1 antibody inhibited the binding of nuclear proteins to the corresponding probes. These data indicate that NS1 up-regulates TNF-alpha transcription via activation of AP-1 and AP-2 in monocytic cells. The molecular mechanisms of NS1-mediated TNF-alpha expression would explain the pathogenesis of B19-associated inflammation.Journal of Virology 07/2002; 76(11):5395-403. · 5.40 Impact Factor -
Article: Quantitative analysis of a MDR1 transcript for prediction of drug resistance in acute leukemia.
[show abstract] [hide abstract]
ABSTRACT: Assessing the drug resistance of leukemic cells is important for treatment of leukemia. We developed a quantitative reverse transcription (RT)-PCR method for multidrug resistance 1 (MDR1) and multidrug resistance-related protein 1 (MRP1) transcripts to evaluate drug resistance, and applied it to clinical samples. The cutoffs for copy numbers of MDR1 and MRP1 transcripts were defined based on copy numbers in healthy bone marrow mononuclear cells. To confirm that the cutoffs reflected biological resistance, we established vincristine (VCR)-resistant K562 sublines that showed various degrees of drug resistance and examined the correlation between the copy numbers of these transcripts and the biological resistance of these clones. In addition, we compared the sensitivity and specificity of quantitative RT-PCR to a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometric (FCM) analysis. The defined cutoff for copy numbers of MDR1 transcripts corresponded with the degree of biological resistance of VCR-resistant K562 sublines. Clinical study revealed that the concentrations of MDR1 mRNA in all relapsed patients with acute myelogenous leukemia (AML) were above the cutoff. Moreover, both AML and acute lymphoblastic leukemia patients with high MDR1 mRNA expression at diagnosis tended to show a low remission rate and short remission periods. No association was observed between the amounts of MRP1 transcripts and clinical outcomes. The specificity and sensitivity of quantitative RT-PCR for MDR1 were superior to the MTT assay and FCM analysis. These results suggest the efficacy of this quantitative analysis of MDR1 transcripts for the prediction of clinical drug resistance in acute leukemia.Clinical Chemistry 07/2002; 48(6 Pt 1):811-7. · 7.91 Impact Factor -
Article: Psychological profiles and health status in Japanese female patients with systemic lupus erythematosus: the Miyagi Lupus Collaborative Study.
[show abstract] [hide abstract]
ABSTRACT: Psychological factors have been suspected to be associated with the development of systemic lupus erythematosus (SLE) and patient's health status. However, psychological profiles among Japanese patients with SLE have been poorly understood. We started a prospective study of female patients with SLE in 1995. Using the baseline data from 279 patients in this prospective study, we cross-sectionally analyzed the relations of clinical factors and social factors to psychological factors, and the association between psychological factors and mental and physical health status. We used the Japanese notion ikigai as an indicator of mental health, and ambulatory activity as an indicator of their physical health, respectively. To measure psychological factors, the short-form of the Eysenck Personality Questionnaire-Revised (short EPQ-R) and the Multidimensional Health Locus of Control (HLOC) scale were used. Active phase of the disease was significantly related to the neuroticism score in the short EPQ-R. Educational level was inversely related to the scores of powerful others and chance HLOC belief. As for health status, the internal HLOC belief was significantly associated with ikigai, and the chance HLOC belief was inversely associated with ambulatory activity. The scores on the short EPQ-R (Extraversion/Introversion and Neuroticism) were exclusively related to ikigai. This study suggests that psychological factors may have effects on both the development of SLE and patient's health status.Journal of Epidemiology 04/2002; 12(2):55-63. · 1.86 Impact Factor -
Article: Primary marginal zone lymphoma of the thymus accompanied by chromosomal anomaly 46,X,dup(X)(p11p22).
[show abstract] [hide abstract]
ABSTRACT: We report a case of primary marginal zone lymphoma in the thymus of a 34-year-old woman. She was initially suspected of having a mediastinal plasmacytoma because of the presence of dominantly proliferating plasmacytic cells in a small fragment obtained by thoracoscopic biopsy, and an elevated level of serum monoclonal IgA. However, histology of the tissue obtained by a subsequent open surgical biopsy revealed diffuse proliferation of atypical monocytoid B-lymphocyte-like cells, which showed prominent plasmacytic differentiation and a close association with thymic epithelial cells consistent with the histology of a marginal zone lymphoma of the thymus. These lymphoma cells were positive for CD19, CD20, IgA, and kappa, and negative for CD5, CD10, and other T/NK-cell and myelomonocyte antigens. Both G-banded and spectral karyotyping analyses revealed the lymphoma cells carried a chromosomal anomaly, 46,X,dup(X)(p11p22). Although large cell type B-cell lymphoma in the thymus (mediastinal diffuse large B-cell lymphoma), which is categorized as a definite subtype in revised European-American classification of lymphoid neoplasms and the new World Health Organization classification, is not infrequent, primary marginal zone lymphoma of the thymus is extremely rare. To our knowledge, this is the first case report of primary marginal zone lymphoma of the thymus with a detailed chromosomal analysis.Cancer Genetics and Cytogenetics 04/2002; 133(2):142-7. · 1.39 Impact Factor -
Article: Nucleotide alteration of retinoblastoma protein-interacting zinc finger gene, RIZ, in human leukemia.
[show abstract] [hide abstract]
ABSTRACT: The retinoblastoma protein-interacting zinc finger gene (RIZ) is a zinc-finger type DNA binding protein and is postulated as a member of the nuclear protein-methyltransferase superfamily. RIZ gene encodes for two proteins, RIZ1 and RIZ2. While RIZ1 contains the N-terminal PR (PRDI-BF1 and RIZ homologous)-domain, RIZ2 lacks it. RIZ1 is now considered as a tumor suppressor. We analyzed nucleotide alteration of RIZ gene in human leukemia. The results revealed a single nucleotide polymorphism (SNP), T1704 to A, near the conserved Rb-binding domain, leading to an amino acid change, Asp283 to Glu. Interestingly, 17 of 21 leukemia cell lines are homozygous for the T1704 allele whereas only 2 of 20 normal subjects are homozygous for the allele. In addition, one base pair deletion in the poly (A)9 tract in the coding region near the C-terminal zinc-fingers was identified, resulting in frameshift, in 1 out of 17 leukemia cell lines, but no mutation in samples from 15 patients with acute lymphoblastic leukemia (ALL) and 6 patients with adult T cell leukemia (ATL). In the PR or SH3 (src homology 3) domain of the RIZ gene, no mutation was found. These findings suggest that RIZ may be a possible target of structural alteration leading to leukemia.The Tohoku Journal of Experimental Medicine 04/2002; 196(3):193-201. · 1.24 Impact Factor -
Article: Autoantibodies to fibrillin 1 in systemic sclerosis: Ethnic differences in antigen recognition and lack of correlation with specific clinical features or HLA alleles
[show abstract] [hide abstract]
ABSTRACT: Objective We previously reported the presence of autoantibodies to the extracellular matrix protein, fibrillin 1, in sera from patients with systemic sclerosis (SSc). These autoantibodies appeared to be highly disease-specific but had significantly different frequencies among ethnic groups. The aims of this study were 3-fold: 1) to determine whether sera from SSc patients of different ethnic backgrounds recognized different antigenic epitopes of fibrillin 1, 2) to determine whether sera from patients with polymyositis/dermatomyositis (PM/DM) with or without interstitial lung disease (ILD) also produced these antibodies, and 3) to determine any correlation of anti–fibrillin 1 antibodies with specific clinical features of SSc, other autoantibodies, or HLA class II alleles in a prospectively studied cohort of SSc patients with early (<5 years' duration) disease (the Genetics versus Environment In Scleroderma Outcome Study [GENISOS] cohort).Methods Three recombinant peptides accounting for the N-terminal end, proline-rich C region, and epidermal growth factor–like calcium-binding (EGF-cb) domains of fibrillin 1 were used in a radioimmunoassay to screen sera from a large group of SSc and PM/DM patients and ethnically matched controls.ResultsThe majority of Choctaw American Indians, Japanese, and African Americans with SSc produced IgM and/or IgG autoantibodies to one or more recombinant fibrillin 1 proteins, while <50% of Caucasians with SSc showed seroreactivity. There were striking ethnic differences in fibrillin 1 antigenic epitope recognition among these ethnic groups. African American SSc sera recognized primarily the N-terminal end, and Caucasian sera mostly recognized the EGF-cb repeats and the proline-rich C region. In contrast, most Choctaw American Indian and Japanese SSc sera appeared to recognize 2 or 3 epitopes, respectively. PM/DM patient sera did not recognize any of the fibrillin 1 epitopes regardless of the presence of ILD. In the prospective, multiethnic GENISOS cohort, the presence of anti–fibrillin 1 antibodies did not correlate with any major clinical manifestations, other autoantibodies, or HLA class II alleles.Conclusion There are striking ethnic differences in antigenic epitope specificity of anti–fibrillin 1 antibodies in patients with SSc, and the majority of SSc patients, except for Caucasians, produce antibodies to fibrillin 1. The antifibrillin response thus far remains specific for scleroderma syndromes, but it does not correlate with any major clinical features, other autoantibodies, or HLA class II alleles.Arthritis & Rheumatism 10/2000; 43(11):2464 - 2471. · 7.87 Impact Factor -
Article: A novel mutation of the erythroid‐specific δ‐aminolaevulinate synthase gene in a patient with X‐linked sideroblastic anaemia
[show abstract] [hide abstract]
ABSTRACT: A novel missense mutation, A1754G, in exon 11 of the erythroid-specific δ-aminolaevulinate synthase gene (ALAS2) was identified in a Japanese male with sideroblastic anaemia. ALAS activity in bone marrow cells of the patient was reduced to 53.3% of the normal control. Consistent with this finding, activity of a bacterially expressed ALAS2 mutant protein harbouring this mutation was 19.5% compared with the normal control, but was increased up to 31.6% by the addition of pyridoxal 5′-phosphate (PLP) in vitro. RFLP analysis with Bsp HI restriction revealed that his mother was a carrier of the mutation. These findings suggest that A1754G mutation was inherited in this family in a manner consistent with X-linked inheritance, and is responsible for sideroblastic anaemia in the patient.British Journal of Haematology 06/1999; 106(1):175 - 177. · 4.94 Impact Factor -
Article: Rheumatoid arthritis, type 1 diabetes, and Graves' disease after acute parvovirus B19 infection.
The Lancet 366(9487):780. · 38.28 Impact Factor -
Article: Choroiditis in systemic lupus erythematosus: systemic steroid therapy and focal laser treatment.
[show abstract] [hide abstract]
ABSTRACT: To report a rare case of choroiditis in association with systemic lupus erythematosus (SLE). A 49-year-old woman with a 17-year history of SLE experienced acute vision impairment of her left eye during the remission stage of systemic SLE. Fundus examination revealed a gray-white subretinal exudate with serous retinal detachment. Angiographic examination disclosed choroidal inflammation at the macula and a breakdown of the blood retinal barrier. Retinal burns were applied to the subretinal exudate with an argon laser as in the treatment of central serous retinopathy. Afterward, her visual acuity showed prompt recovery due to the regression of the serous retinal detachment. However, the choroidal inflammation remained until the systemic condition was controlled with steroid therapy. Laser treatment of a subretinal exudate was helpful for the resolution of serous detachment and the prompt improvement of visual acuity, whereas systemic steroid therapy was effective for choroidal inflammation. Systemic steroid therapy is thought to be effective for SLE choroiditis; however, this therapy is also known to cause serous retinal detachment. Thus, in SLE choroiditis, laser photocoagulation at a leakage point, in addition to systemic steroid therapy, may be helpful for the prompt restoration of vision in patients with serous retinal detachment.Japanese Journal of Ophthalmology 47(3):312-5. · 0.92 Impact Factor -
Article: Over-expression of Flt3 induces NF-κB pathway and increases the expression of IL-6
[show abstract] [hide abstract]
ABSTRACT: Activating mutations or over-expression of the Flt3 is prevalent in acute myeloblastic leukemia (AML), associated with activation of Ras/MAP kinase and other signaling pathways. In this study, we addressed the role of Flt3 in the activation of nuclear factor-kappa B (NF-κB), which is a target molecule of these kinase pathways. In BaF3 cells stably expressing Flt3, a NF-κB-responsive reporter was upregulated and its target gene, IL-6, was increased by the involvement of Flt3-ERK/MAPK-NF-κB pathway. Furthermore, we found a modest positive correlation (r = 0.35, p = 0.096) between Flt3 and IL-6 mRNA expression in 24 AML specimens. These results suggest a role of Flt3 over-expression in NF-κB pathway.Leukemia Research. -
Article: Genomic structure and regulation of a novel human gene, Klp1
[show abstract] [hide abstract]
ABSTRACT: Klp1 (K562 cells-derived leucine zipper-like protein 1) is a transcription factor which binds to the coproporphyrinogen oxidase promoter regulatory element (GGACTACAG). In order to clarify the function of Klp1, we determined the complete human Klp1 genomic structure and regulatory element in the promoter region. The gene spans about 2.4 kb and has three exons. Its promoter region has multiple GC boxes, E2F binding site, one cAMP response element (CRE), and no TATA box with multiple transcription initiation sites, which is characteristic of housekeeping and growth regulating genes. Promoter analysis showed that the promoter was more active in K562 cells entered into the cell cycle by serum stimulation than quiescent cells. Further promoter analysis revealed that CRE at −42 is essential for full promoter activity, and c-Jun and activation transcription factor 1/cAMP response element binding protein 1 proteins bind to this element. These structural characteristics and the promoter function suggest that Klp1 may play a role in cell cycle regulation.Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression 1522(3):207-211. · 1.70 Impact Factor
Top co-authors
Top Journals
Institutions
-
2002–2011
-
Tohoku University
- • Department of Hematology and Rheumatology
- • Department of Infection Control and Laboratory Diagnostics
Sendai, Kagoshima-ken, Japan
-
-
2002–2004
-
Miyagi Cancer Center
Sendai-shi, Miyagi-ken, Japan
-
