Papers - Hashiguchi, Akinori

Exogenous expression of heat shock protein 90 retards the cell cycle and impairs the heat shock response

Zhao Chen, Hashiguchi Akinori, Kondoh Kensuke, Du Wenglin, Hata Jun-ich, Yamada Taketo

Experimental cell research 275 ( 2 ) 200-214 2002.05

Research paper (scientific journal), Joint Work

Exogenous　expression of heat shock protein 90kDa retards the cell cycle and impairs the heat shock resonse

Zhao　Chen, Hashiguchi　Akinori, Kondoh　Kensuke, Du　Wenlin, Hata　Jun-ichi, Yamada　Taketo

Experimental Cellular Research 275 ( 2 ) 200-214 2002.03

Research paper (scientific journal), Joint Work

Augmentation of megakaryocytopoiesis by hematopoietotic microenviromnment of human granulocyte colony-stimulating factor transgenic mice

Fujita T, Yamada T, Hashiguchi A, Fukushima S, Kondoh K, Fujimoto J, Hata J,

Experimental Hematology 29 ( 8 ) 1010-1018 2001.08

Research paper (scientific journal), Joint Work

Augmentation of megakaryocytopoiesis within the hematopoietic microenvironment of human granulocyte colony-stimulating factor transgenic mice

T Fujita, T Yamada, A Hashiguchi, S Fukushima, K Kondoh, J Fujimoto, J Hata

EXPERIMENTAL HEMATOLOGY (ELSEVIER SCIENCE INC)  29 ( 8 ) 1010 - 1018 2001.08

Joint Work,  ISSN  0301-472X

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Objective. Megakaryocytopoiesis was dramatically augmented in human granulocyte colony-stimulating factor transgenic mice (G-Tg) compared to littermates. We examined the characteristics of megakaryocytes and megakaryocyte progenitor cells in these mice.
Materials and Methods. The numbers of colony-forming unit megakaryocytes (CFU-MK) and megakaryocytes in hematopoietic organs were counted. The megakaryocytes of G-Tg were examined ultrastructurally, and bone marrow transplantation studies using congenic G-Tg (Ly5.2) and C57BL/6 (Ly5.1) were performed. The number of day-14 colony-forming unit spleen (CFU-S) that contained megakaryocytes in [Ly5.1 > G-Tg] and [G-Tg > Ly5.1] mice also was counted.
Results. The number of CFU-MK increased markedly in the spleen, bone marrow, and peripheral blood. The number of megakaryocytes in the spleen and bone marrow also were increased in G-Tg mice. Ultrastructural analyses revealed that megakaryocytes in G-Tg mice were immature. Bone marrow transplantation studies of [Ly5.1 > G-Tg] mice resulted in a significantly increased number of megakaryocytes compared to [G-Tg > Ly5.1] mice. The number of day-14 CFU-S that contained megakaryocytes was increased markedly in [Ly5.1 > G-Tg] mice compared to [G-Tg > Ly5.1] mice. In vitro differentiation of megakaryocytes in [Ly5.1 > G-Tg] mice was induced by interleukin-11 and thrombopoietin.
Conclusion. The results showed that the hematopoietic marrow microenvironment of G-Tg is important in augmenting megakaryocytopoiesis. [Ly5.1 > G-Tg] mice are potentially useful as a source of murine megakaryocytes and their progenitors. (C) 2001 International Society for Experimental Hematology. Published by Elsevier Science Inc.

A case of generalized Hailey-Hailey disease with fatal liver injury

Amagai M, Kobayashi M, Wakabayashi K, Hakuno M, Hashiguchi A, Nishikawa T, Hata J

The Keio Journal of Medicine 50 ( 2 ) 109-116 2001.06

Research paper (scientific journal), Joint Work

A case of generalized Hailey-Hailey disease with fatal liver injury

Amagai M, Kobayashi M, Wakabayashi K, hakuno M, Hashiguchi A, Nishikawa T, Hata J

Keio Journal of Medicine 50 ( 2 ) 109-116 2001.06

Research paper (scientific journal), Joint Work

Augmentation of human leukemic cell invasion by activation of a small GTP-binding protein Rho

Fukushima S, Yamada T, Hashiguchi A, Nakata Y, Hata J

Experimental Hematology (ELSEVIER SCIENCE INC)  28 ( 4 ) 391-400 - 400 2000.04

Research paper (scientific journal), Joint Work,  ISSN  0301-472X

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Objective. The functions of a small GTP-binding protein, Rho, in human leukemic cell invasion was investigated in vivo and in vitro.
Materials and Methods. Human leukemic KM3 and Reh cells (derived from B-cell-type common acute lymphoid leukemias) were inoculated into severe combined immundeficiency (SCID) mice, Alteration of invasion in SCID mice inoculated with KM3 cells that were introduced with the expression vector for Rho Val14 (Rho V14), an activated mutant form of Rho, was observed.
Results. SCID mice inoculated with KM3 and Reh cells developed paraplegia 21 days after inoculation. All died by day 26-27, The leukemic cells were localized to bone marrow and around the spinal cord, with no infiltration into peripheral blood, spleen, liver, thymus, or lymph nodes. SCID mice inoculated with Rho V14-transfected KM3 cells showed a 5-day reduction in the time to paraplegia and death compared with SCID mice inoculated with hygromycin-resistance gene-transfected KM3 (hyg(r)) cells. In addition, the mice inoculated with Rho V14 cells showed leukemic cell infiltration, not only into bone marrow and around the spinal cord but also into peripheral blood, liver, and spleen. There were no in vitro or in vivo differences in growth rates of Rho V14 and hyg(r) cells. However, the Rho V14 cells showed markedly increased cell adhesion compared to the hygr cells.
Conclusion. Results suggest that Rho activation accelerates human leukemic cell invasion via augmentation of cell adhesion. (C) 2000 International Society for Experimental Hematology, Published by Elsevier Science Inc.

Function of 90 kDa heat shock protein in cellular differentiation of human embryonal carcinoma cells

Yamada T, Hashiguchi A, Fukudshim S, Kakita Y, Umezawa A, Maruyama T, Hata J

In Vitro Cellular and Developmental Biology. Animal (SOC IN VITRO BIOLOGY)  36 ( 2 ) 139-146 - 146 2000.02

Research paper (scientific journal), Joint Work,  ISSN  1071-2690

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Heat shock proteins (HSPs) have been recognized as molecules that maintain cellular homeostasis during changes in the environment. Here we report that HSP90 functions not only in stress responses but also in certain aspects of cellular differentiation. We found that HSP90 showed remarkably high expression in undifferentiated human embryonal carcinoma (EC) cells, which Here subsequently dramatically down-regulated during in vitro cellular differentiation, following retinoic acid (RA) treatment, at the protein level. Surprisingly, heat shock treatment also triggered the clown-regulation of HSP90 within 48 h at the protein level. Furthermore, the heat treatment induced cellular differentiation into neural cells. This down-regulation of HSP90 by heat treatment was shifted to an up-regulation pattern after cellular differentiation in response to RA treatment. In order to clarify the functions of HSP90 in cellular differentiation, we conducted various experiments, including overexpression of HSP90 via gene transfer. We showed that the RA-induced differentiation of EC cells into a neural cell lineage was inhibited by overexpression of the HSP90 alpha or -beta isoform via the gene transfer method. On the other hand, the overexpression of HSP90 beta alone impaired cellular differentiation into trophoectoderm. These results show that down-regulation of HSP90 is a physiologically critical event in the differentiation of human EC cells and that specific HSP90 isoforms may be involved in differentiation into specific cell lineages.

Apoptosis of human embryonal carcinoma cells with in vitro differentiation

Yamada T, Suzuki N, Hiraoka N, Matsuoka K, Fukushima S, Hashiguchi A, Hata J

Cell Struct Funct (JAPAN SOC CELL BIOLOGY)  21 ( 1 ) 53-61 - 61 1996

Research paper (scientific journal), Joint Work,  ISSN  0386-7196

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An in vitro model of apoptosis and differentiation in human embryonal carcinoma (EC) cells was developed to study the mode of cell death and mechanisms of cell death in early development. Death of these cells was induced by treatment with retinoic acid (RA) under the same conditions as those for induction of differentiation. The manner of this cell death was apoptosis, not necrosis, with the morphological criterion for apoptosis. Serum deprivation likewise caused apoptosis in both undifferentiated and differentiated EC cells. In differentiated EC cells, DNA fragmentation was observed in a smear pattern lacking the ladder pattern typically associated with apoptosis. However, in differentiated EC cells, DNA fragmentation occurred in various sizes.
The expression of a carbohydrate antigen, Le(Y), a reported marker of apoptotic cancer cells, was increased by the treatment with RA. However, two-color analysis by flow cytometry with nick end labelling method revealed that Le(Y) expression was closely correlated with cellular differentiation but not apoptosis after RA treatment in the human EC cell system. Collection of Le(Y) positive cells by the magnetic bead method demonstrated that this expression was not due to apoptosis but rather to differentiation. On the other hand, Le(Y) expression associated with apoptosis was induced by serum deprivation in both undifferentiated and differentiated EC cells. These results show that a subpopulation of undifferentiated EC cells takes the apoptotic pathway by induction of differentiation.
The results also suggest that the population of cells taking an apoptotic pathway differs from a population of cells taking a differentiation pathway. This in vitro system for apoptosis in human EC cells will be useful for studies concerning apoptosis or programmed cell death in human developmental biology.