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Makiko Takizawa

Publications and source records attributed to Makiko Takizawa.

12 recordsLinked to original sources
PubMed2006

Sacroiliitis as an initial manifestation of acute myelogenous leukemia.

Sacroiliitis is the most pathognomonic and earliest manifestation of ankylosing spondylitis. We herein report a 28-year-old female patient who presented with sacroiliitis as an initial manifestation of acute myelogenous leukemia (AML). She had a 3-month history of anemia and walking difficulty. Bone marrow findings revealed an increase of blasts with trilineage dysplasia. Although she was initially diagnosed with myelodysplastic syndrome (MDS), blasts rapidly increased and AML developed 1 month after the diagnosis of MDS with Sacroiliitis. Induction chemotherapy failed to induce a complete remission of AML, but it did effectively treat the sacroiliitis. However, the sacroiliitis relapsed when the leukemia cells progressed thereafter. Oral corticosteroids helped ameliorate the sacroiliitis. She underwent bone marrow transplantation (BMT) from an HLA-identical sister during a nonremission period; however, the leukemic cells began to rapidly increase from day 30 after BMT. The close relationship between the occurrence of sacroiliitis and AML suggested that autoimmune sacroiliitis was a paraneoplastic phenomenon of AML in this patient. Although autoimmune disorders develop in a substantial number of MDS patients, they are rarely observed in de novo AML. No previous report has described sacroiliitis as the initial manifestation of de novo AML.

Adrenal Cortex Hormones↗
PubMed2005

Fate redirection of hippocampal astrocytes toward neuronal lineage by aggregate culture.

Mammalian cells that have been committed to a certain cell lineage cannot be directed to other lineages. However, some astrocytes in the mammalian brains have been reported to represent plasticity to redirect to other cell lineages. We found that mouse hippocampal astrocytes cultured in aggregate forms of "astrosphere", redirected to MAP2-positive immature neurons. In astrospheres, basic HLH factors positively regulating neuronal differentiation were up-regulated and Id3 inhibiting basic HLH factors was down-regulated. Ectopic Id3 induction repressed redirection of astrocytes to a neuronal lineage, suggesting that astrosphere formation induced plasticity of astrocytes by changing the gene expression patterns.

Animals↗
PubMed2005

Pericardial graft vs. host disease in a patient with myelodysplastic syndrome following peripheral blood stem cell transplantation.

A patient with myelodysplastic syndrome developed pericardial effusion 20 month after allogenic peripheral blood stem cell transplantation. Sclerotic and erythematous skin lesions were observed over the face and extremities, and a diagnosis of chronic graft vs. host disease (GVHD) was made based on skin biopsy findings. Pericardial fluid contained numerous CD8+/HLA-DR+ lymphocytes, but no leukaemic cells. Tumour necrosis factor alpha (TNFalpha) and soluble Fas (sFas) levels were highly elevated in both the effusion and serum. The patient was treated with methylprednisolone and tacrolimus. Skin GVHD improved rapidly associated with resolution of pericardial effusion and reductions in cytokine levels. We concluded that pericardial effusion was due to pericarditis and was a manifestation of chronic GVHD in this patient, and that cytotoxic lymphocytes and specific cytokines played significant roles.

Adult↗
PubMed2005

[Unclassified mature T cell leukemia with cerebriform nuclei].

A 53 year-old male visited our hospital for evaluation of his leukocytosis, which was first diagnosed more than 6 years previously. He was asymptomatic and there were no remarkable findings on physical and laboratory examinations except for the lymphocytosis. Abnormal lymphocytes with deep folded nuclei were seen on light microscopy, whose phenotype was CD3+, CD4-, CD8-, CD7-, CD16 , CD56-, CD45RO+ and CD45RA- . Electron microscopy revealed 'cerebriform nuclei' which were characteristic of Sézary cells. Adult T cell leukemia (ATL) and Sézary syndrome (SS) were ruled out because of the negative HTLV-1 test and the absence of skin lesions, respectively. T-prolymphocytic leukemia (T-PLL), which is characterized by a marked increase in leukocytes having a CD7-phenotype and a progressive fatal course, was also excluded. Recently, the TCL1 onco-protein has been shown to be overexpressed in progressive T-PLL but not in other mature T cell leukemias including Sézary syndrome. Peripheral mononuclear cells in the present patient did not overexpress TCL1. In its morphology and phenotypes, our case resembled 'Sézary cell leukemia (SCL)' but the clinical course was much more indolent. This case did not match any of the mature T cell leukemias defined in the WHO classification.

Cell Nucleus↗
PubMed2004

Spred-2 suppresses aorta-gonad-mesonephros hematopoiesis by inhibiting MAP kinase activation.

In midgestation mouse embryos, the aorta-gonad-mesonephros (AGM) region generates hematopoietic stem cells and definitive hematopoiesis is regulated by cell-cell interaction and signaling molecules. We showed that a Ras/mitogen-activated protein (MAP) kinase signaling-specific inhibitor and a dominant negative mutant Ras blocked the production of CD45+ hematopoietic cells in embryonic day 11.5 AGM culture, indicating an essential role for the MAP kinase pathway in AGM hematopoiesis. Overexpression of the Ras/MAP kinase pathway regulator, Spred-2, in the AGM culture significantly reduced the number of CD45+ cells. In contrast, production of CD45+ cells from the AGM region of Spred-2-null mice was up-regulated as compared with wild-type littermates. Furthermore, Spred-2-deficient mice exhibited elevated hematopoietic colony formation from vascular endothelial-cadherin+ cells. These data indicate that Spred-2 functions as a negative regulator of AGM hematopoiesis by inhibiting hematopoietic cytokine signaling.

Animals↗
PubMed2004

Negative regulation of hematopoiesis by the fused in myeloproliferative disorders gene product.

The t(8;13) translocation, found in a rare and aggressive type of stem cell myeloproliferative disorder, leads to the generation of a fusion protein between the N-terminal gene product of fused in myeloproliferative disorders (FIM)/ZNF198 and the fibroblast growth factor receptor 1 (FGFR1) kinase domain. The chimeric protein was reported to have constitutively activated tyrosine kinase activity. However, little is known about a role of FIM in hematopoietic cell regulation. Here we show that FIM protein is ubiquitously expressed in mouse embryonic tissues but much less in hematopoietic cells. We also show that forced expression of FIM inhibits the emergence of hematopoietic cells in the cultured mouse aorta-gonad-mesonephros (AGM) region on embryonic day (E) 11.5, where definitive hematopoiesis is first found during embryogenesis. These results suggest that the expression level of FIM determines the development of hematopoiesis during mouse ontogeny.

Animals↗
PubMed2004

Enhanced release of prostaglandin D2 during re-incubation of RAW 264.7 macrophage-like cells after treatment of both lipopolysaccharide and non-steroidal anti-inflammatory drugs.

RAW 264.7 macrophage-like cells are known to release prostaglandins (PGs), mainly PGD(2) to the culture medium after lipopolysaccharide (LPS)-treatment. This release was inhibited by non-steroidal anti-inflammatory drugs (NSAIDs), which are known to inhibit prostaglandin H(2) synthase (PGHS) activity. In this study, we examined the effect of removal of NSAID after induction of PGHS with LPS, on the release of PGs, which has not been studied well. Re-incubation of RAW 264.7 cells after treatment of both LPS and NSAIDs resulted in enhanced release of PGD(2) compared with the cells pretreated with LPS alone. Besides, PGHS activity was detectable in these cell homogenates and the amount of PGHS-2 protein showed similar changes to PGD(2) release. However, addition of NSAIDs again in the re-incubation period almost completely inhibited the PGD(2) release but increased the amount of PGHS-2 protein to the higher levels. Various types of NSAIDs used in this study showed similar effects on the changes in PGD(2) release and PGHS-2 protein amounts, except those on PGHS activity in cell homogenates; while indomethacin, aspirin, and NS-398 inhibited it, but nimesulide and acetaminophen did not. These results seem to suggest an importance for the caution that the enhanced induction of PGHS-2 protein and the concomitant release of PGs release would occur after removal of the NSAID not only from the medium in in vitro experiments but also from therapeutic prescription.

Animals↗
PubMed2003

Genomic organization and characterization of the mouse ELYS gene.

Differentiation of hematopoietic stem cells into blood cells is controlled by several transcription factors. Recently, we identified a putative transcription factor, ELYS (for embryonic large molecule derived from yolk sac), using a subtraction strategy. During mouse embryogenesis, ELYS transcripts were predominantly expressed in hematopoietic tissues, such as the yolk sac, aorta-gonad-mesonephros (AGM), and liver. Here, we report the cloning and characterization of the mouse ELYS gene. The ELYS gene spanned approximately 60kb encoding 36 exons, and was assigned between D1Mit315 and D1Mit458 markers in chromosome 1. The transcription initiation site was identified as the G residue located 670bp upstream of the translation start codon. A region downstream of the transcriptional start site contributed to high promoter activity. This region contained potential DNA elements for transcription factors such as GATA-1, -2, -3, heat shock factor (HSF) 2, and NF-kappaB, which are known to play important roles in hematopoietic events.

Animals↗
PubMed2003

Requirement of gp130 signaling for the AGM hematopoiesis.

OBJECTIVE: Definitive hematopoiesis starts in the aorta-gonad-mesonephros (AGM) region during mouse development and remarkably expands in the liver at a later stage of ontogeny. gp130 is a signal transducing receptor component shared by all the IL-6 family cytokines, whose gene ablation in mouse results in the significant reduction in the fetal liver hematopoiesis. The present study aims to evaluate the role of gp130 signaling in the fetal mouse AGM hematopoiesis. METHODS AND MATERIALS: Mouse AGM regions from the wild-type and gp130-deficient mice on embryonic day 11.5 were dissociated and cultured with a mixture of cytokines, including one which activates gp130. Wild-type human gp130 and its mutant constructs were introduced into cultured gp130-deficient AGM cells using retrovirus system. To further analyze gp130 downstream signaling, a dominant-negative mutant of STAT3 was also introduced. RESULTS: The gp130 deficiency in the culture of fetal mouse AGM cells resulted in the failure of the expansion of the c-kit(+), Sca-1(+), and lineage markers(-) population. Such failure was rescued by introduction of a wild-type gp130 expression construct but not its mutant constructs having no ability to activate STAT3. In the normal AGM cell culture, introduction of a dominant-negative form of STAT3 in which Y(705) was changed to phenylalanine suppressed the expansion of hematopoietic cell colonies. CONCLUSION: gp130 plays an indispensable role in the expansion of hematopoietic precursor cells in the fetal mouse AGM. In particular, the activation of STAT3 by gp130 is found to be important in this process.

Animals↗
PubMed2003

Regulation of hematopoietic development in the aorta-gonad-mesonephros region mediated by Lnk adaptor protein.

Development of hematopoietic cells in the aorta-gonad-mesonephros (AGM) region in the midgestation mouse embryo involves a multistep process, sequentially changing from endothelial cell-like cells, including hemangioblasts, into hematopoietic stem cells, progenitors, and/or lineage-committed cells. An adaptor molecule, Lnk, is known to negatively control the production of pro- and pre-B cells and hematopoietic progenitor cells in adult bone marrow. Here we show a role of Lnk in hematopoietic development in the AGM region. Lnk was predominantly expressed in the endothelial cells lining the dorsal aorta at embryonic day 11.5 (E11.5). Overexpression of Lnk in the primary culture of the AGM region at E11.5 suppressed the emergence of CD45+ hematopoietic cells. Point mutation in the SH2 domain of Lnk, which abolishes the binding capability of Lnk to c-Kit upon stimulation with stem cell factor (SCF), led to loss of Lnk-dependent inhibition of hematopoietic cell development in AGM cultures, suggesting Lnk-mediated inhibition of the SCF/c-Kit signaling pathway. In cultured AGM cells from Lnk homozygous mutant mouse embryos, the number of emerged CD45+ cells was 2.5-fold larger than that from heterozygous littermates. Furthermore, aorta cells of E11.5 Lnk homozygous mutant mice also showed enhanced hematopoietic colony-forming activity. Thus, Lnk is a negative regulator of hematopoiesis in the AGM region.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Identification of a novel transcription factor, ELYS, expressed predominantly in mouse foetal haematopoietic tissues.

BACKGROUND: The precise mechanism governing the generation of haematopoietic stem cells still remains to be understood, partly because the molecules required for early haematopoiesis have not fully been identified. RESULTS: We have identified a novel gene expressed in embryonic haematopoietic tissues, designated ELYS (for embryonic large molecule derived from yolk sac), which has no significant homology with any other known molecules. Based on the cDNA sequence, mouse ELYS protein is composed of 2243 amino acid residues and contains an AT-hook DNA-binding domain, eight nuclear localization signals (NLSs) at the C-terminal region, three nuclear export signals (NESs) and two WD repeats at the N-terminal region. ELYS has a potential to shuttle between the cytoplasm and nucleus. When in the nucleus, ELYS is present in the nuclear matrix. Fusions of the yeast GAL4 DNA-binding domain and various ELYS mutants reveal the presence of transcriptional activation and inhibitory domains. The ELYS gene is predominantly expressed in embryonic haematopoietic tissues, i.e. foetal liver, spleen, and thymus, whereas the expression is down-regulated in the adult. In the aorta-gonad-mesonephros (AGM) region of an 11.5 dpc mouse embryo, ELYS is expressed in the endothelium lining the dorsal aorta. In the adult bone marrow, ELYS is notably expressed in the Lin-/c-kit+/Sca-1+ population. CONCLUSIONS: We have reported the isolation and characterization of a novel molecule, ELYS. ELYS seems to be a nuclear transcription factor associated with both early and mature haematopoietic events.

Amino Acid Sequence↗