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ABSTRACT: Intakes of selected vitamins and dietary fiber may influence the clinical course of systemic lupus erythematosus (SLE). Using a cohort study method, we investigated the associations of dietary intake of vitamin B6 and B12, folate, and dietary fiber with the risk of active disease and atherosclerotic vascular events in SLE.
The study included female SLE patients in the Miyagi Lupus Cohort, which was founded in 1995. Dietary nutrients at baseline were estimated by a semiquantitative food frequency questionnaire. The association of each nutrient intake with the risk of active disease was investigated in 216 patients who had inactive disease at baseline. The association with atherosclerotic vascular events was assessed in 196 women who had inactive disease and no history of atherosclerotic diseases at baseline.
Forty-three cases of active disease were identified during 9966 person-months of follow-up (1995-1999). During 19 575 person-months of follow-up (1995-2005), 20 atherosclerotic vascular events were documented. The Cox proportional hazards model revealed an inverse association between vitamin B6 intake and the risk of active disease (hazard ratio for the highest as compared with the lowest tertile, 0.41; 95% confidence interval, 0.18-0.97; P for trend = 0.04). An inverse association was also found for dietary fiber intake (P for trend = 0.01). However, no significant association was observed between intakes of these nutrients and the risk of atherosclerotic vascular events.
Higher intake of vitamin B6 and dietary fiber may prevent the occurrence of active disease in SLE.
Journal of Epidemiology 04/2011; 21(4):246-54. · 1.86 Impact Factor
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ABSTRACT: Anti-dsDNA Abs are highly specific indicators of systemic lupus erythematosus (SLE) and play a pathogenic role in lupus nephritis. Human anti-dsDNA Abs are most likely generated by an Ag-driven mechanism. However, the Ag responsible for triggering anti-dsDNA Ab production has not been identified. To search for proteins that are cross-reactive with anti-dsDNA Abs, we screened a cDNA library from a patient with SLE with single-chain Fv of O-81 human anti-ss/dsDNA mAb by using a two-hybrid system. Homocysteine-induced ER protein (Herp), an endoplasmic reticulum (ER) stress-inducible ER membrane protein, was identified and shown to bind to original O-81 Ab and human lupus anti-dsDNA Abs. Some IgG purified from patients with active SLE by Herp-immobilized affinity chromatography bound to dsDNA. BALB/c mice immunized with Herp showed IgG anti-dsDNA Abs, IgG anti-nucleosome Abs, and glomerular IgG deposition. Herp reactivity was strongly positive in a proportion of PBLs from patients with active SLE, but undetectable in those from healthy controls. Moreover, activation of caspases was observed in the Herp-positive cells, implying that ER stress-induced apoptosis likely occurs in patients with active SLE. Herp is exposed on blebs of ER stress-induced apoptotic cells, suggesting that Herp can be recognized by immune cells. These results indicate that Herp mimics structural determinants of DNA immunologically and can be immunogenic in vivo. Thus, Herp represents a candidate autoantigen for anti-DNA Abs. This study may help explain how common environmental factors induce the production of anti-DNA Abs and contribute the development of SLE.
The Journal of Immunology 02/2010; 184(6):3276-83. · 5.79 Impact Factor
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Hiroto Ohguchi,
Toshiya Tanaka,
Aoi Uchida,
Kenta Magoori,
Hiromi Kudo,
Insook Kim,
Kenji Daigo,
Iori Sakakibara,
Masashi Okamura,
Hideo Harigae, Takeshi Sasaki,
Timothy F Osborne,
Frank J Gonzalez,
Takao Hamakubo,
Tatsuhiko Kodama,
Juro Sakai
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ABSTRACT: Type 1 iodothyronine deiodinase (Dio1), a selenoenzyme catalyzing the bioactivation of thyroid hormone, is highly expressed in the liver. Dio1 mRNA and enzyme activity levels are markedly reduced in the livers of hepatocyte nuclear factor 4alpha (HNF4alpha)-null mice, thus accounting for its liver-specific expression. Consistent with this deficiency, serum T4 and rT3 concentrations are elevated in these mice compared with those in HNF4alpha-floxed control littermates; however, serum T3 levels are unchanged. Promoter analysis of the mouse Dio1 gene demonstrated that HNF4alpha plays a key role in the transactivation of the mouse Dio1 gene. Deletion and substitution mutation analyses demonstrated that a proximal HNF4alpha site (direct repeat 1 [TGGACAAAGGTGC]; HNF4alpha-RE) is crucial for transactivation of the mouse Dio1 gene by HNF4alpha. Mouse Dio1 is also stimulated by thyroid hormone signaling, but a direct role for thyroid hormone receptor action has not been reported. We also showed that thyroid hormone-inducible Krüppel-like factor 9 (KLF9) stimulates the mouse Dio1 promoter very efficiently through two CACCC sequences that are located on either side of HNF4alpha-RE. Furthermore, KLF9 functions together with HNF4alpha and GATA4 to synergistically activate the mouse Dio1 promoter, suggesting that Dio1 is regulated by thyroid hormone in the mouse through an indirect mechanism requiring prior KLF9 induction. In addition, we showed that physical interactions between the C-terminal zinc finger domain (Cf) of GATA4 and activation function 2 of HNF4alpha and between the basic domain adjacent to Cf of GATA4 and a C-terminal domain of KLF9 are both required for this synergistic response. Taken together, these results suggest that HNF4alpha regulates thyroid hormone homeostasis through transcriptional regulation of the mouse Dio1 gene with GATA4 and KLF9.
Molecular and cellular biology 07/2008; 28(12):3917-31. · 6.06 Impact Factor
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ABSTRACT: Several reports of bone marrow dysplasia in patients with systemic lupus erythematosus (SLE) have been published. However, the reports are restricted primarily to descriptions of the erythroid lineage; no follow-up studies have been reported, and the clinical significance of the dysplasias is unknown. Therefore, in the present study, the dysplasias noted in bone marrow aspirates obtained from SLE patients were characterized.
The smears of bone marrow aspirates obtained from 17 SLE patients who had bone marrow aspiration due to cytopenia (WBC < 1,500/microl, or Hb < 10.5 g/dl, or platelet count < 10 x 10(4)/microl) were examined retrospectively. Of the 17 patients, 4 had a repeat bone marrow aspiration during follow-up. Clinical and laboratory data were obtained from the medical records.
Of the 17 SLE patients, 12 had dysplasias, including: erythroid cell multinuclearity (trinuclear or more) (5 patients), megaloblastoid changes (4), pseudo-Pelger abnormalities (6), annular nuclear myeloid cells (2), separated nuclear megakaryocytes (4), and micromegakaryocytes (5). In the 4 patients who had follow-up bone marrow aspiration, these dysplasias were correlated with disease activity; some abnormalities disappeared with remission of SLE. Diffuse proliferative glomerulonephritis (3 patients) and cerebral lupus/neuropsychiatric lupus (4 patients) were seen only in patients with dysplasia.
This study found that bone marrow dysplasia can be observed in all lineage cells of SLE patients, and that the dysplasia is reversible during the course of the disease. The presence of dysplasias appears to be associated with disease severity.
Internal Medicine 01/2008; 47(8):737-42. · 0.94 Impact Factor
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ABSTRACT: GATA-2 is a transcription factor expressed in stem and progenitor cells of various cell lineages. In this study, we examined the role of GATA-2 in the differentiation of adipocytes, which are the main components of the microenvironment for hematopoiesis. Suppression of GATA-2 in TBR343, a preadipocytic stromal cell line, resulted in the acceleration of adipocyte differentiation. Conversely, overexpression of GATA-2 induced the resistance of adipocyte differentiation. In addition, regulatory elements of the GATA-2 gene in TBR343 are the same as those in hematopoietic cells. These results suggest that GATA-2 maintains a hematopoietic microenvironment by regulating the differentiation of adipocytes.
Biochemical and Biophysical Research Communications 01/2008; 364(2):383-7. · 2.48 Impact Factor
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ABSTRACT: Sex-related differences (SrD) are a general characteristic of human autoimmune diseases. There is an increasing body of evidence that suggests a link between sex-related hormones and autoimmune onsets. Here, through a genetic approach using a lupus mouse model, we attempted to show the involvement of genetic factors in the development of SrD in autoimmune diseases. Using MRL/lpr x (MRL/lpr x C57BL/6.Fas(lpr))F1 (MBN2) mice, the whole genome was searched to identify linkage loci to autoimmune phenotypes inherited from a lupus MRL/Mp.Fas(lpr) (MRL/lpr) strain of mice, which exhibits glomerulonephritis, splenomegaly and antinuclear autoantibody. The genome-wide association study confirmed four linkage loci on chromosomes 4, 7, 13, and 17. Furthermore, differential analyses performed using male and female groups of MBN2 mice revealed that two loci located on chromosomes 4 (41-72 cM, MRL/lpr allele) and 7 (4-21 cM, B6/lpr allele) were male specific and suppressed autoimmune phenotypes. Notably, the sum effect of the two loci adequately explained a range of SrD developed in the MBN2 mice. Our present findings suggest the presence of a male-predominant mechanism underlying the development of SrD in autoimmunity, depending on the effects of autosomal loci under an undefined male-specific condition.
European Journal of Immunology 11/2007; 37(10):2787-96. · 5.10 Impact Factor
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ABSTRACT: Hyperhomocysteinemia has been reported as one of the risk factors for vascular damage. Homocysteine induces endoplasmic reticulum (ER) stress in vascular endothelial cells, which is followed by production of homocysteine-induced ER protein (Herp). Herp has been thought to have a protective role against ER stress and inhibition of apoptosis, but the details are still obscure. To detect Herp protein precisely, we established a murine hybridoma clone producing an anti-human Herp monoclonal antibody (mAb), named HT2. The specific binding of HT2 mAb to Herp was confirmed by enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. In ELISA, HT2 mAb was able to bind to Herp in a dose-dependent manner, and its binding was interrupted by recombinant Herp. In Western blot analysis, a 54-kDa band corresponding to Herp was detected with HT2 mAb in the membrane fraction of untreated HeLa cells, and its expression was remarkably increased in ER-stressed HeLa cells that had been treated with homocysteine, thapsigargin, or 2-mercaptoethanol. Importantly, the signal was eliminated by absorption of HT2 mAb with recombinant Herp prior to incubation with the blotted membrane. Immunofluorescence microscopy revealed that HT2 mAb stained the perinuclear cytoplasm of ER-stressed HeLa cells, which was similar to the staining pattern with anti-KDEL (Lys-Asp-Glu-Leu) mAb that recognizes the ER. In contrast, untreated HeLa cells were weakly stained with HT2 mAb. Thus, the HT2 mAb is useful in the quantitative and/or qualitative detection of Herp and to study the role of Herp at a variety of pathological states.
The Tohoku Journal of Experimental Medicine 09/2007; 212(4):431-7. · 1.24 Impact Factor
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ABSTRACT: Nasal natural killer (NK)/T cell lymphoma is a rare entity of non-Hodgkin's lymphoma which mostly occurs in East Asian countries. The advanced disease above clinical stage III is often refractory to the radiation and chemotherapies, remission is transient even if achieved, and median survival is about 12 months. Thus the prognosis of advanced NK/T cell lymphoma is generally poor, however, the promising results of allogeneic hematopoietic stem cell transplantation for advanced NK/T cell lymphoma have been recently reported. In most of these cases, stem cell sources were human leukocyte antigen (HLA) matched donors and alternative sources were seldom used. We report here a case of a 36-year-old woman who was diagnosed as having an extranodal NK/T cell lymphoma, nasal type. The patient achieved a complete remission after 2 cycles of chemotherapy including Carboplatin, Etoposide, Ifosfamide, and Dexamethasone, but 3-months later relapsed during the search for HLA-matched unrelated donors. She received unrelated cord blood transplantation (CBT) in the second remission achieved by a regimen containing L-asparaginase. The conditioning regimen was 12 Gy of total body irradiation, high-dose cytarabin and cyclophosphamide. FK506 and methotrexate were used for graft-versus-host disease (GVHD) prophylaxis. GVHD involving the intestine and the oral mucosa was observed, but improved without additional immunosuppressive therapies. The patient remains in remission 33 months after CBT. Cord blood thus could be an appropriate stem cell source for patients with advanced NK/T lymphoma who have no HLA matched donors.
The Tohoku Journal of Experimental Medicine 05/2007; 211(4):395-9. · 1.24 Impact Factor
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ABSTRACT: Chronic myelogenous leukemia (CML) is a hematological malignancy that is characterized by the chromosome anomaly, t(9;22)(q34;q11). By this chromosomal translocation, a novel activated tyrosine kinase, BCR-ABL chimeric protein, is generated, and the protein is causative of the disease. Recently, Imatinib mesylate targeting to a BCR-ABL chimeric protein has been developed, and shown to achieve complete remission at a high rate. Patients are currently required to receive a fixed dose, 400 mg daily; however, it is possible that some of patients can maintain their remission with reduced doses of imatinib. In this study, we determined levels of BCR-ABL transcript in CML patients by real-time quantitative polymerase chain reaction analysis, and explored the possibility of individualization of therapeutic doses of imatinib. Thirty-five CML patients, including 17 newly diagnosed patients, 16 patients pre-treated with interferon-alpha, and 2 relapsed patients after allogeneic transplantation, were treated with imatinib. Complete cytogenetic response was achieved in 31 (89%) patients. Major molecular response (MMR) was achieved in 21 (60%). Complete molecular response (CMR) was achieved in 7 (20%). Imatinib was discontinued in 2 patients, one patient with MMR due to noncompliance and other patient sustaining CMR, but both patients relapsed 7 and 13 months later, respectively. The doses of imatinib were reduced in 7 patients due to its side effects, but 4 out of the 7 patients have sustained MMR, and 2 of them have sustained CMR for more than 23 months. These results indicate that some patients are able to maintain MMR with low-dose imatinib.
The Tohoku Journal of Experimental Medicine 01/2007; 210(4):355-63. · 1.24 Impact Factor
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ABSTRACT: Nucleolar spindle-associated protein (NuSAP), a recently characterised microtubule-associated protein, appears to participate in cell cycle regulation. It has been demonstrated that NuSAP is expressed preferentially in the erythroid lineage in haematopoietic cells. To characterise its role in erythropoiesis, we examined the expression profile of the NuSAP gene. In fractionated murine erythroblasts, NuSAP mRNA was remarkably more abundant in the subset corresponding to immature erythroblasts (TER119(+)CD71(high)) than mature erythroblasts (TER119(+)CD71(low)), and it was significantly increased in TER119(+) cells from in vivo phlebotomised mice compared with control mice. Furthermore, during erythroid maturation of mouse erythroleukaemia (MEL) cells by dimethylsulfoxide, NuSAP mRNA was increased at 24-72 h. These results suggested that the NuSAP gene might contribute to the expansion of immature erythroblast pool. The regulatory mechanism of NuSAP gene was investigated using MEL cells. Sequence analysis revealed that NuSAP promoter has four CCAAT boxes, an Sp1 element, a GATA-like element, a CACCC element, a Myb element and lacks a TATA box. Promoter analyses demonstrated that duplicated CCAAT boxes located at -81/-85 and -30/-34 were essential for promoter activity. Furthermore, the promoter was trans-activated by NF-YA through these elements. These results suggest that NuSAP might play an important role in erythroid proliferation under the control of NF-Y.
British Journal of Haematology 12/2006; 135(4):583-90. · 4.94 Impact Factor
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Junichi Kameoka,
Ryo Ichinohasama,
Hiroko Inoue,
Joji Yamamoto,
Hisayuki Yokoyama,
Yasuo Tomiya,
Minami Yamada,
Kenichi Ishizawa,
Hideo Harigae,
Takashi Sawai, Takeshi Sasaki
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ABSTRACT: CD26/dipeptidyl peptidase IV is a cell surface antigen with multiple biological functions. Although its involvement in tumor biology has been suggested, the significance of its expression in malignant lymphoma has not been clarified in detail. This study examined the expression of CD26 and cell surface adenosine deaminase (ADA) in 42 cases of Hodgkin's lymphoma (HL) and T-cell lymphoma by immunohistochemistry on frozen sections. CD26 was expressed in three of 14 cases of HL, in four of eight cases of anaplastic large cell lymphoma (ALCL), in two of nine cases of peripheral T-cell lymphoma, in one of six cases of lymphoblastic lymphoma and in none of three cases of adult T-cell lymphoma/leukemia. Expression of cell surface ADA was fully correlated with the expression of CD26 and expression of CD26/ADA in ALCL and HL was also completely correlated with the expression of p80 and epithelial membrane antigen. Of 10 CD26-positive patients, seven had fever and elevated CRP at initial diagnosis and over a median follow-up of 61 months (range, 7 - 152 months) only three survived. This study suggested that CD26 is selectively expressed on ALK-positive, but not on ALK-negative, ALCL and HL. This is also the first report to demonstrate that ADA is coexpressed with CD26 on the cell surface of malignant neoplasms in vivo.
Leukemia and Lymphoma 11/2006; 47(10):2181-8. · 2.58 Impact Factor
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ABSTRACT: Flt3 internal tandem duplication (Flt3-ITD) is a prevalent mutation in acute myeloid leukemia (AML). Flt3-ITD constitutively activates various signaling pathways, including a mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway. Arsenic trioxide (ATO) and MEK inhibition were recently reported to interact synergistically to induce apoptosis in AML cells. In this study, we aimed to clarify whether ATO and Flt3 inhibition would be a more specific and efficient therapy for Flt3-ITD cells. We demonstrate that the combination of ATO and an Flt3 inhibitor, AG1296, profoundly inhibits the growth of Flt3-ITD cells and induces their apoptosis. We further revealed that this combined treatment potently inhibits the ERK activity that might be responsible for cell growth. Moreover, using the Chou-Talalay method, we observed a synergistic growth-inhibitory effect for ATO and AG1296 in Flt3-ITD cells (BaF3-Flt3-ITD, MV4-11, and PL-21 cells), but not in Flt3 wild-type cells (RS4-11 and NB4 cells), for almost all dose ranges tested. Our results provide an experimental basis for a specific and efficient therapy for Flt3-ITD cells that involves combined treatment with Flt3 inhibitors and ATO.
International Journal of Hematology 11/2006; 84(3):256-61. · 1.27 Impact Factor
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ABSTRACT: Tetrasomy 8 is a rare chromosomal abnormality in acute leukemia, and it has recently been considered as a poor prognostic factor. A 20-year-old woman was admitted because of purpura on the upper and lower limbs in February 2002. On admission, her leukocyte count was 6.5 x 10(9)/l with 66% of blasts, the hemoglobin level was 11.2 g/dl, and the platelet count was 101 x 10(9)/l. The bone marrow aspirate contained 85.6% of peroxidase-negative, alpha-naphthyl-butyrate esterase-positive, and CD4+ CD56+ blast cells. Karyotypic analysis of the bone marrow cells showed 48, XY, + 8, + 8[17]/47, XY, +8[3]. The patient was diagnosed as having AML (M5a), and treatment with daunorubicin (70 mg x 5 days) and cytosine arabinoside (150 mg x 7 days) resulted in a complete remission. She relapsed four months later, however, with an extramedullary tumor in T12. Remission could not be achieved, and the patient underwent allogeneic peripheral blood stem cell transplantation from her HLA-identical mother. Her clinical course was almost uneventful except for a phlegmon in the right leg, but on day 49 a relapse occurred, and she died of acute renal failure on day 73. This case strongly illustrates the characteristic of tetrasomy 8 as a poor prognostic factor in acute leukemia.
[Rinshō ketsueki] The Japanese journal of clinical hematology 09/2006; 47(8):770-6.
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Shori Abe,
Tadao Funato,
Shinichiro Takahashi,
Hisayuki Yokoyama,
Joji Yamamoto,
Yasuo Tomiya,
Minami Yamada-Fujiwara,
Kenichi Ishizawa,
Junichi Kameoka,
Mitsuo Kaku,
Hideo Harigae, Takeshi Sasaki
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ABSTRACT: Resistance to cytosine arabinoside (Ara-C) is a major problem in the treatment of patients with acute myeloid leukemia (AML). In order to investigate the mechanisms involved in Ara-C resistance, the gene expression profile of Ara-C-resistant K562 human myeloid leukemia cells (K562/AC cells) was compared to that of Ara-C-sensitive K562 cells (K562 cells) by using a cDNA microarray platform. Correspondence analysis demonstrated that insulin-like growth factor I (IGF-I) gene was upregulated in K562/AC cells. The biological significance of IGF-I overexpression was further examined in vitro. When K562 cells were incubated with IGF-I ligand, they were protected from apoptosis induced by Ara-C. In contrast, a significant inhibition of growth and increase of apoptosis of K562/AC cells were induced by IGF-I receptor neutralizing antibody, or suramin, a nonspecific growth factor antagonist. Moreover, from the analysis of 27 AML patients, we have shown that IGF-I expression levels are higher in patients at refractory stage, after Ara-C combined chemotherapy, than those in patients at diagnosis. These results suggest that the inhibition of IGF-I and its downstream pathway is a valuable therapeutic approach to overcome Ara-C resistance in AML.
The Tohoku Journal of Experimental Medicine 08/2006; 209(3):217-28. · 1.24 Impact Factor
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ABSTRACT: GATA transcription factors have been shown to play important roles in hematopoiesis. GATA-2 is expressed in stem and progenitor cells, and has been speculated to control the proliferation and maintain the immaturity of these cells. To examine whether the function of GATA-2 is changeable according to the differentiation stage, we established GATA-2 overexpressing subclones of K562, which is a leukemic cell line committed to the erythroid lineage. Via an increase in the GATA-2 expression level, the expression levels of erythroid-specific genes including alpha-, beta-, and gamma-globin were increased compared to control cells, while the expression level of GATA-1 was unchanged. Expression of the transferrin receptor was also increased in GATA-2 overexpressing K562 cells when examined by flow cytometry. In addition, the heme content of GATA-2 overexpressing K562 cells was more than 2 times higher than control cells. Chromatin immunoprecipitation analysis showed that GATA-2 protein binding to the GATA element in alpha-globin LCR was increased in GATA-2 overexpressing K562 cells. These findings suggest that GATA-2 could induce erythroid-specific genes without competition with GATA-1 when expressed in erythroid-committed cells, and thus further suggest that temporal and spatial regulation may be important for displaying specific functions of GATA-2.
International Journal of Hematology 08/2006; 84(1):38-42. · 1.27 Impact Factor
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ABSTRACT: Over-expression of the Flt3 is prevalent in acute myeloblastic leukemia (AML), playing a role in leukemogenesis while decreased expression of PU.1 induces AML in mice model. Therefore, we speculated that there is an inverse relationship between these two factors. To clarify this, we measured the expression level of Flt3 and PU.1 in 24 primary AML specimens. As a result, there is a significant negative correlation between Flt3 and PU.1 (r=-0.43, p<0.05). Furthermore, we revealed that flt3 gene promoter is suppressed by the over-expression of PU.1, suggesting that PU.1 is a potential suppressor of flt3 gene promoter.
Leukemia Research 06/2006; 30(6):659-64. · 2.92 Impact Factor
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ABSTRACT: We previously established 33 bone marrow stromal cell lines from SV40 T-antigen transgenic mice. Of these, 27 clones supported erythroid colony formation, while 6 did not. The objective of this study is to identify the molecules that determine these erythroid colony-forming activities.
We compared gene expression profiling by DNA microarray between cell lines that support erythropoiesis (E(+); TBR9, 184, 31-2) and cell lines that do not (E(-); TBR17, 33, 511). Among the differentially expressed genes, we selected candidate genes with results of quantitative reverse transcriptase polymerase chain reaction, and examined the effect of small interfering RNA (siRNA) and the addition of exogenous proteins on the erythroid colony formation.
Out of 7226 genes examined, 138 and 282 genes were upregulated and downregulated in E(+) by threefold or more, respectively. We have selected one of the upregulated genes, tenascin-C (TN-C), as a candidate. Expressions of TN-C in E(+) were all higher than the three E-cell lines, with a mean of 3.6-fold. The number of erythroid colonies in the presence of TN-C siRNA was significantly lower than that of control siRNA in TBR9 (20.7 +/- 6.3 vs 4.7 +/- 4.8 colonies; p = 0.01) and in TBR184 (13.3 +/- 5.3 vs 0.3 +/- 0.5; p = 0.02). Moreover, addition of exogenous TN-C enhanced the number of erythroid colonies in TBR184 (13.3 +/- 3.5 vs 20.0 +/- 2.0; p = 0.04) and in TBR31-2 (7.5 +/- 3.1 vs 13.5 +/- 2.6; p = 0.03).
These results suggest that TN-C is responsible for determining the stromal cell-dependent erythropoiesis.
Experimental Hematology 05/2006; 34(4):519-27. · 2.90 Impact Factor
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Seikagaku. The Journal of Japanese Biochemical Society 04/2006; 78(3):242-9. · 0.04 Impact Factor
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ABSTRACT: Stanniocalcin (STC) is a glycoprotein hormone that regulates calcium levels in fish. The related human protein stanniocalcin-1 (STC-1) is expressed in multiple organs including the ovary, prostate, kidney, and thyroid. Human STC-1 expression is enhanced by neural cell differentiation, bone formation, and cell proliferation. Recently, quantitative RT-PCR analysis showed high levels of STC-1 mRNA in the blood of patients with cancer as compared with those in the blood of volunteers without cancer. The STC-1 mRNA expression in blood is closely related to tumor size in breast cancer, micrometastases of hepatocellular carcinoma, and minimal residual disease in leukemia. This brief review describes the diagnostic significance of STC-1 as a molecular marker for human cancer.
Rinsho byori. The Japanese journal of clinical pathology 04/2006; 54(3):213-20.
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Shuming Chen,
Naoto Ishii,
Shouji Ine,
Syuichi Ikeda,
Taku Fujimura,
Lishomwa C Ndhlovu,
Pejman Soroosh,
Kohtaro Tada,
Hideo Harigae,
Junichi Kameoka,
Noriyuki Kasai, Takeshi Sasaki,
Kazuo Sugamura
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ABSTRACT: Adult T cell leukemia (ATL) is an aggressive neoplastic disease, in which a quarter of the patients develop opportunistic infections due to cellular immunodeficiency. However, the underlying mechanism responsible for the immunosuppression has remained unclear. Recent studies have demonstrated that the leukemia cells from a subset of patients with ATL express Foxp3, a specific marker for CD25+CD4+ regulatory T (Treg) cells, which regulate the immune response by suppressing CD4+ T cell functions. However, whether there is a functional resemblance between ATL cells that have Foxp3 expression and Treg cells is still unknown. In this report, we confirmed the high expression of Foxp3 in leukemia cells from 5 of 12 ATL patients and demonstrated that ATL cells from 3 patients suppressed the proliferation of CD4+ T cells. Similarly, one of six HTLV-I-infected cell lines showed both high Foxp3 expression and suppressive activity. Like Treg cells, the suppression induced by the ATL cells from two patients and the HTLV-infected cell line appeared to be mediated by a cell-cell contact-dependent mechanism. Nevertheless, among the ATL cells that strongly expressed Foxp3, those from two of the five patients showed no apparent suppressive activity. Furthermore, retroviral transfection of Foxp3 did not confer any suppressive function on low Foxp3-expressing HTLV-I-infected cell lines. These results indicate that Foxp3 may be essential but is not sufficient for the Treg-cell-like suppressive activity of ATL cells and HTLV-I-infected cell lines.
International Immunology 03/2006; 18(2):269-77. · 3.41 Impact Factor
