Motoko Yamaguchi

Summary

Affiliation: Mie University
Country: Japan

Publications

  1. doi request reprint Current and future management of NK/T-cell lymphoma based on clinical trials
    Motoko Yamaguchi
    Department of Hematology and Oncology, Mie University Graduate School of Medicine, 2 174 Edobashi, Tsu, Mie 514 8507, Japan
    Int J Hematol 96:562-71. 2012
  2. ncbi request reprint Analysis of clonal relationship using single-cell polymerase chain reaction in a patient with concomitant mantle cell lymphoma and multiple myeloma
    M Yamaguchi
    Second Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan
    Int J Hematol 73:383-5. 2001
  3. ncbi request reprint De novo CD5-positive diffuse large B-cell lymphoma: clinical characteristics and therapeutic outcome
    M Yamaguchi
    Second Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan
    Br J Haematol 105:1133-9. 1999
  4. doi request reprint Phase I study of dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapy for advanced-stage, relapsed or refractory extranodal natural killer (NK)/T-cell lymphoma and leukemia
    Motoko Yamaguchi
    Mie University Graduate School of Medicine, 2 174 Edobashi, Tsu, Mie 514 8507, Japan
    Cancer Sci 99:1016-20. 2008
  5. doi request reprint De novo CD5+ diffuse large B-cell lymphoma: results of a detailed clinicopathological review in 120 patients
    Motoko Yamaguchi
    Department of Hematology and Oncology, Mie University Graduate School of Medicine, 2 174 Edobashi, Tsu, Mie 514 8507, Japan
    Haematologica 93:1195-202. 2008
  6. ncbi request reprint De novo CD5-positive diffuse large B-cell lymphoma of the temporal bone presenting with an external auditory canal tumor
    Shoko Ogawa
    Department of Hematology, Mie University Graduate School of Medicine, Edobashi, Tsu
    Intern Med 45:733-7. 2006
  7. ncbi request reprint Hemostatic abnormalities and leukocyte activation caused by infection in patients with malignant lymphoma during chemotherapy
    Yuko Kamikura
    Second Department of Internal Medicine, Mie University Hospital, Tsu, Japan
    Thromb Res 117:671-9. 2006
  8. doi request reprint Phase I/II study of concurrent chemoradiotherapy for localized nasal natural killer/T-cell lymphoma: Japan Clinical Oncology Group Study JCOG0211
    Motoko Yamaguchi
    Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Mie, Japan
    J Clin Oncol 27:5594-600. 2009
  9. ncbi request reprint [Long-term remission of a nasal NK/T-cell lymphoma patient with massive involvement of the orbita and liver dysfunction]
    Fumihiko Monma
    Department of Hematology and Oncology, Mie University Graduate School of Medicine
    Rinsho Ketsueki 50:44-8. 2009
  10. ncbi request reprint Intravascular large B-cell lymphoma (IVLBCL): a clinicopathologic study of 96 cases with special reference to the immunophenotypic heterogeneity of CD5
    Takuhei Murase
    Department of Internal Medicine, Nishio Municipal Hospital, 6 Kami awara, Kumamicho, Nishio, Aichi, and Department of Hematology, Mie University Graduate School of Medicine, Tsu, Japan
    Blood 109:478-85. 2007

Collaborators

Detail Information

Publications105 found, 100 shown here

  1. doi request reprint Current and future management of NK/T-cell lymphoma based on clinical trials
    Motoko Yamaguchi
    Department of Hematology and Oncology, Mie University Graduate School of Medicine, 2 174 Edobashi, Tsu, Mie 514 8507, Japan
    Int J Hematol 96:562-71. 2012
    ..As in the cases of other aggressive lymphomas, prospective clinical trials with adequate statistical considerations should be conducted to improve the prognosis of patients with ENKL...
  2. ncbi request reprint Analysis of clonal relationship using single-cell polymerase chain reaction in a patient with concomitant mantle cell lymphoma and multiple myeloma
    M Yamaguchi
    Second Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan
    Int J Hematol 73:383-5. 2001
    ..Sequence analysis revealed no clonal relationship between MCL and MM in our patient...
  3. ncbi request reprint De novo CD5-positive diffuse large B-cell lymphoma: clinical characteristics and therapeutic outcome
    M Yamaguchi
    Second Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan
    Br J Haematol 105:1133-9. 1999
    ..These findings suggest that de novo CD5-positive DLBL forms a distinct subgroup of DLBL...
  4. doi request reprint Phase I study of dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapy for advanced-stage, relapsed or refractory extranodal natural killer (NK)/T-cell lymphoma and leukemia
    Motoko Yamaguchi
    Mie University Graduate School of Medicine, 2 174 Edobashi, Tsu, Mie 514 8507, Japan
    Cancer Sci 99:1016-20. 2008
    ..Although its safety and efficacy require further evaluation, we recommend a SMILE chemotherapy dose level of 1 for further clinical studies...
  5. doi request reprint De novo CD5+ diffuse large B-cell lymphoma: results of a detailed clinicopathological review in 120 patients
    Motoko Yamaguchi
    Department of Hematology and Oncology, Mie University Graduate School of Medicine, 2 174 Edobashi, Tsu, Mie 514 8507, Japan
    Haematologica 93:1195-202. 2008
    ..The aim of this retrospective study was to clarify the histopathological spectrum and obtain new information on the therapeutic implications of CD5(+) DLBCL...
  6. ncbi request reprint De novo CD5-positive diffuse large B-cell lymphoma of the temporal bone presenting with an external auditory canal tumor
    Shoko Ogawa
    Department of Hematology, Mie University Graduate School of Medicine, Edobashi, Tsu
    Intern Med 45:733-7. 2006
    ..The occurrence of malignant lymphoma in the temporal bone, which is an extremely unusual site, may have depended on the peculiarity of CD5-positive DLBCL...
  7. ncbi request reprint Hemostatic abnormalities and leukocyte activation caused by infection in patients with malignant lymphoma during chemotherapy
    Yuko Kamikura
    Second Department of Internal Medicine, Mie University Hospital, Tsu, Japan
    Thromb Res 117:671-9. 2006
    ..Activated leukocytes and granulocyte elastase may elicit a hypercoagulable state and ARDS in patients with malignant lymphoma during chemotherapy...
  8. doi request reprint Phase I/II study of concurrent chemoradiotherapy for localized nasal natural killer/T-cell lymphoma: Japan Clinical Oncology Group Study JCOG0211
    Motoko Yamaguchi
    Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Mie, Japan
    J Clin Oncol 27:5594-600. 2009
    ..To explore a more effective treatment for localized nasal natural killer (NK)/T-cell lymphoma, we conducted a phase I/II study of concurrent chemoradiotherapy...
  9. ncbi request reprint [Long-term remission of a nasal NK/T-cell lymphoma patient with massive involvement of the orbita and liver dysfunction]
    Fumihiko Monma
    Department of Hematology and Oncology, Mie University Graduate School of Medicine
    Rinsho Ketsueki 50:44-8. 2009
    ..L-asparaginase was administered in the final course of chemotherapy. There is no evidence of recurrence 56 months after diagnosis...
  10. ncbi request reprint Intravascular large B-cell lymphoma (IVLBCL): a clinicopathologic study of 96 cases with special reference to the immunophenotypic heterogeneity of CD5
    Takuhei Murase
    Department of Internal Medicine, Nishio Municipal Hospital, 6 Kami awara, Kumamicho, Nishio, Aichi, and Department of Hematology, Mie University Graduate School of Medicine, Tsu, Japan
    Blood 109:478-85. 2007
    ..459), and thrombocytopenia less than 100x10(9)/L (P=.012, HR: 2.427) were independently unfavorable prognostic factors; CD5 positivity was not. Beyond immunophenotypic diversity, IVLBCL constitutes a unique group with aggressive behavior...
  11. ncbi request reprint Clinicopathologic significance of loss of CD19 expression in diffuse large B-cell lymphoma
    Miho Kimura
    Department of Hematology, Mie University Graduate School of Medicine, Tsu, Japan
    Int J Hematol 85:41-8. 2007
    ..034, generalized Wilcoxon test). Our findings demonstrate that loss of CD19 expression in DLBCL is associated with elevated serum LDH levels and a poor prognosis, especially during the early follow-up period...
  12. doi request reprint Gene expression profiling of peripheral T-cell lymphoma including gammadelta T-cell lymphoma
    Kana Miyazaki
    Department of Hematology, Mie University Graduate School of Medicine, Tsu, Japan
    Blood 113:1071-4. 2009
    ..Our results indicate that hepatosplenic gammadeltaTCL is a distinct form of peripheral TCL and suggest that nonhepatosplenic gammadeltaTCLs are heterogeneous in gene expression...
  13. ncbi request reprint De novo CD5+ diffuse large B-cell lymphoma: a clinicopathologic study of 109 patients
    Motoko Yamaguchi
    Second Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan
    Blood 99:815-21. 2002
    ..Of particular interest is that CD5+ DLBCL was characterized by a survival curve significantly inferior to that for patients with CD5- DLBCL (P =.0026). These findings suggest that CD5+ DLBCL may constitute a unique subgroup of DLBCL...
  14. doi request reprint Phase II study of SMILE chemotherapy for newly diagnosed stage IV, relapsed, or refractory extranodal natural killer (NK)/T-cell lymphoma, nasal type: the NK-Cell Tumor Study Group study
    Motoko Yamaguchi
    Mie University Graduate School of Medicine, Tsu, Japan
    J Clin Oncol 29:4410-6. 2011
    ....
  15. doi request reprint Gene expression profiling of diffuse large B-cell lymphoma supervised by CD21 expression
    Kana Miyazaki
    Department of Haematology and Oncology, Mie University Graduate School of Medicine, Tsu, Japan
    Br J Haematol 142:562-70. 2008
    ..Immunohistochemical analysis of 216 DLBCLs confirmed that overall survival of surface (s) IgM+ DLBCLs was significantly poorer than that of sIgM- DLBCLs (P = 0.013)...
  16. ncbi request reprint Characterization of the myosin-binding subunit of smooth muscle myosin phosphatase
    H Shimizu
    First Department of Internal Medicine, Mie University School of Medicine, Japan
    J Biol Chem 269:30407-11. 1994
    ..Myosin binding and binding to the catalytic subunit are properties of a 58,000-Da fragment that represents the N-terminal part of the molecule...
  17. ncbi request reprint Expression of CD29 on lymphoma cells and/or CD36 on microvascular endothels correlates with high serum LDH level in diffuse large B-cell lymphomas (DLBCLs) and is frequent in de novo CD5-positive DLBCLs
    Satoshi Ueno
    The Second Department of Internal Medicine, Mie University School of Medicine, Tsu, Mie 514 8507, Japan
    Int J Oncol 27:1241-6. 2005
    ..Furthermore, CD29 and mvCD36 expression should be evaluated in relation to the intravascular growth pattern of lymphoma cells...
  18. ncbi request reprint [Multiple myeloma relapsed or progressed as plasmacytoma after allogeneic reduced-intensity stem cell transplantation: report of three cases]
    Yuka Sugimoto
    Department of Hematology and Oncology, Mie University Graduate School of Medicine
    Rinsho Ketsueki 50:289-94. 2009
    ..That may be because conditioning regimen doesn't include total body irradiation, or GVM is ineffective in plasmacytoma, but effective in bone marrow. Here, we report clinical course of these three cases with some consideration...
  19. ncbi request reprint [Angioimmunoblastic T-cell lymphoma occurring four months after autologous peripheral blood stem cell transplantation with high-dose chemotherapy for follicular lymphoma]
    Kana Miyazaki
    Second Department of Internal Medicine, Mie University School of Medicine
    Rinsho Ketsueki 46:1065-70. 2005
    ..Clinical and histopathological findings showed that the FL and AILT in this case were not concomitant. It is thought that in this case, the AILT developed as a post-transplant lymphoproliferative disorder after auto-PBSCT for the FL...
  20. ncbi request reprint Extra nodal NK/T-cell lymphoma nasal type that responded to DeVIC combination chemotherapy
    Eriko Nomura
    Department of Dermatology, Mie University, Faculty of Medicine, Tsu, Japan
    J Dermatol 32:204-9. 2005
    ..Although there may be a limitation of effects on metastasis of tumors in the central nervous system, radiation and DeVIC combination therapy is a potent therapeutic method for ENKL...
  21. ncbi request reprint [Diffuse large B-cell lymphoma of the knee occurring 70 years after tuberculous arthritis]
    Satoshi Ueno
    Second Department of Internal Medicine, Mie University School of Medicine
    Rinsho Ketsueki 45:304-7. 2004
    ..The patient was treated with chemotherapy (CHOP) followed by radiotherapy, and obtained partial remission. There is no evidence of progression seven months after diagnosis...
  22. ncbi request reprint Inhibitory phosphorylation site for Rho-associated kinase on smooth muscle myosin phosphatase
    J Feng
    First Department of Internal Medicine, Mie University School of Medicine, Tsu, Mie 514 8507, Japan
    J Biol Chem 274:37385-90. 1999
    ..In summary, these results offer strong support for a physiological role of Rho-kinase in regulation of MP activity...
  23. ncbi request reprint Molecular cloning and analysis of the 5'-flanking region of the human MYPT1 gene
    H Machida
    First Department of Internal Medicine, University School of Medicine, Tsu, Mie, Japan
    Biochim Biophys Acta 1517:424-9. 2001
    ..Luciferase reporter assays showed the presence of two regions for positive elements and one for a negative element...
  24. ncbi request reprint CD21S antigen expression in tumour cells of diffuse large B-cell lymphomas is an independent prognostic factor indicating better overall survival
    Shoko Ogawa
    Second Department of Internal Medicine, Mie University School of Medicine, 2 174 Edobashi, Tsu, Mie 514 8507, Japan
    Br J Haematol 125:180-6. 2004
    ..These findings indicate that CD21S expression of DLBCL tumour cells is a useful prognostic factor for survival...
  25. ncbi request reprint Contrast-enhanced ultrasound examination of lymph nodes in different types of lymphoma
    Kazunori Nakase
    Second Department of Internal Medicine, Mie University School of Medicine, 2 174 Edobashi, Tsu, Mie 514 8507, Japan
    Cancer Detect Prev 30:188-91. 2006
    ....
  26. ncbi request reprint Identification of human CPI-17, an inhibitory phosphoprotein for myosin phosphatase
    K Yamawaki
    First Department of Internal Medicine, Mie University School of Medicine, Tsu, Mie, 514 8507, Japan
    Biochem Biophys Res Commun 285:1040-5. 2001
    ..The cloned human CPI-17 gene indicated 4 coding exons and CPI-17beta was an alternative splice variant due to deletion of the second exon. FISH analysis located the human CPI-17 gene on chromosome 19q13.1...
  27. ncbi request reprint Isolation of monoclonal antibodies directed against the V protein of human parainfluenza virus type 2 and localization of the V protein in virus-infected cells
    M Nishio
    Department of Microbiology, Mie University School of Medicine, Japan
    Med Microbiol Immunol 188:79-82. 1999
    ..The P and NP proteins were organized in numerous granules in the cytoplasm of hPIV-2 infected cells. In contrast, the V protein showed diffuse nuclear and cytoplasm distributions...
  28. ncbi request reprint Phosphorylation of CPI-17, an inhibitory phosphoprotein of smooth muscle myosin phosphatase, by Rho-kinase
    M Koyama
    First Department of Internal Medicine, Mie University School of Medicine, Tsu, Mie 514 8507, Japan
    FEBS Lett 475:197-200. 2000
    ..Thus, CPI-17 as a substrate of Rho-kinase could be involved in the Ca(2+) sensitization of smooth muscle contraction as a downstream effector of Rho-kinase...
  29. ncbi request reprint Multiple pulmonary emboli with pulmonary hypertension caused by effort thrombosis and effective balloon venoplasty of the subclavian vein
    N Isaka
    First Department of Internal Medicine, Mie University School of Medicine, Japan
    Jpn Circ J 65:920-2. 2001
    ..Pulmonary embolism is not a rare complication of upper extremity deep vein thrombosis and should be managed as aggressively as lower extremity deep vein thrombosis...
  30. ncbi request reprint Mapping of domains on the human parainfluenza type 2 virus P and NP proteins that are involved in the interaction with the L protein
    M Nishio
    Department of Microbiology, Mie University School of Medicine, 2 174, Edobashi, Tsu Shi, Mie Ken, 514 8507, Japan
    Virology 273:241-7. 2000
    ....
  31. ncbi request reprint Pulse-spray pharmacomechanical thrombolysis for proximal deep vein thrombosis
    N Yamada
    First Department Cardiovascular Division of Internal Medicine, Mie University School of Medicine, Tsu, Mie, Japan
    Eur J Vasc Endovasc Surg 31:204-11. 2006
    ..The aim of this study was to evaluate the efficacy, safety, and feasibility of pulse-spray pharmacomechanical thrombolysis to treat proximal deep vein thrombosis (DVT) in conjunction with the placement of a non-permanent IVC filter...
  32. pmc Hemagglutinin-neuraminidase-independent fusion activity of simian virus 5 fusion (F) protein: difference in conformation between fusogenic and nonfusogenic F proteins on the cell surface
    M Tsurudome
    Department of Microbiology, Mie University School of Medicine, Tsu, Mie 514 8507, Japan
    J Virol 75:8999-9009. 2001
    ..The native conformation of L22P may represent an intermediate between native and postfusion conformations of a typical paramyxovirus F protein...
  33. ncbi request reprint Protein kinase C-catalyzed phosphorylation of an inhibitory phosphoprotein of myosin phosphatase is involved in human platelet secretion
    Y Watanabe
    2nd and 1st Departments of Internal Medicine, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan
    Blood 97:3798-805. 2001
    ..Thus, CPI phosphorylation by PKC may participate in inhibiting myosin phosphatase, in addition to the Rho-kinase-mediated regulation of myosin phosphatase, during agonist-induced platelet secretion. (Blood. 2001;97:3798-3805)..
  34. ncbi request reprint Plasma levels of natriuretic peptides in relation to doxorubicin-induced cardiotoxicity and cardiac function in children with cancer
    H Hayakawa
    Department of Pediatrics, Mie University School of Medicine, Tsu, Mie, Japan
    Med Pediatr Oncol 37:4-9. 2001
    ..We examined whether plasma levels of ANP and BNP, in addition to echocardiographic evaluation, can be used as specific markers for doxorubicin-induced cardiotoxic effects in children...
  35. ncbi request reprint Recovery of infectious human parainfluenza type 2 virus from cDNA clones and properties of the defective virus without V-specific cysteine-rich domain
    M Kawano
    Department of Microbiology, Mie University School of Medicine, 2 174 Edobashi, Mie, 514 8507, Japan
    Virology 284:99-112. 2001
    ..Furthermore, the rPIV2V(-) virions showed anomalous in size as compared with rPIV2 virions. These results suggest that the V protein plays an important role in the hPIV2 assembly, maturation, and morphogenesis...
  36. ncbi request reprint Human parainfluenza virus type 2 phosphoprotein: mapping of monoclonal antibody epitopes and location of the multimerization domain
    M Nishio
    Department of Microbiology, Mie University School of Medicine, Japan
    J Gen Virol 78:1303-8. 1997
    ..The oligomer was shown to be a homotrimer by chemical cross-linking experiments...
  37. ncbi request reprint Anaplastic large cell lymphoma associated with Sjögren's syndrome
    H Inaba
    Department of Pediatrics, Mie University School of Medicine, Tsu, Japan
    Leuk Lymphoma 32:183-8. 1998
    ..To the best of our knowledge, this is the first reported case of ALCL presenting concurrently with SjS...
  38. ncbi request reprint Changes in intracellular cytokine levels in newborn and adult lymphocytes induced by HSV-1
    M Ito
    Department of Pediatrics, Mie University School of Medicine, Tsu, Japan
    J Med Virol 56:145-50. 1998
    ..These results demonstrate that HSV-1 enhances intracellular levels of IL-2, IFN-gamma, and TNF-alpha in adult lymphocytes and defective IFN-gamma production in cord blood...
  39. ncbi request reprint A new isoform of human myosin phosphatase targeting/regulatory subunit (MYPT2): cDNA cloning, tissue expression, and chromosomal mapping
    M Fujioka
    First Department of Internal Medicine, Mie University School of Medicine, Japan
    Genomics 49:59-68. 1998
    ..1, compared to the chromosomal location 12q15-q21-2 for MYPT1. It is suggested that the products of the two gene families of myosin phosphatase target subunit may be localized differently among various tissues...
  40. ncbi request reprint Identification of regions on the fusion protein of human parainfluenza virus type 2 which are required for haemagglutinin-neuraminidase proteins to promote cell fusion
    M Tsurudome
    Department of Microbiology, Mie University School of Medicine, Tsu, Japan
    J Gen Virol 79:279-89. 1998
    ..These regions on the PIV-2 F protein may be involved in a putative functional interaction with HN proteins, which is considered to be a prerequisite for cell fusion...
  41. ncbi request reprint Regulation of myosin phosphatase through phosphorylation of the myosin-binding subunit in platelet activation
    K Nakai
    2nd Department of Internal Medicine, Mie University School of Medicine, Tsu Mie, Japan
    Blood 90:3936-42. 1997
    ..These findings suggest a putative mechanism for agonist-induced regulation of myosin phosphatase activity in platelets...
  42. ncbi request reprint Apoptosis of cord blood T lymphocytes by herpes simplex virus type 1
    M Ito
    Department of Pediatrics, Mie University School of Medicine, Tsu, Japan
    J Gen Virol 78:1971-5. 1997
    ..Addition of anti-Fas antibody, anti-Fas-ligand antibody or a mixture of both had no effect on HSV-1-induced apoptosis, indicating that the Fas-Fas-ligand pathway did not contribute to HSV-1-induced apoptosis...
  43. ncbi request reprint Interaction of smooth muscle myosin phosphatase with phospholipids
    M Ito
    First Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan
    Biochemistry 36:7607-14. 1997
    ..This mechanism could be important in localization of myosin phosphatase and in targeting substrates at different loci...
  44. ncbi request reprint Human immunodeficiency virus type-1 envelope glycoprotein gp120 induces expression of fusion regulatory protein (FRP)-1/CD98 on CD4+ T cells: a possible regulatory mechanism of HIV-induced syncytium formation
    S Suga
    Department of Microbiology, Mie University School of Medicine, Japan
    Med Microbiol Immunol 185:237-43. 1997
    ..These results suggest that FRP-1 molecules are induced on CD4+ T cells via CD4-gp120 interaction and may play an important role in regulation of HIV-induced syncytium formation...
  45. ncbi request reprint Mapping of domains on the human parainfluenza virus type 2 nucleocapsid protein (NP) required for NP-phosphoprotein or NP-NP interaction
    M Nishio
    Department of Microbiology, Mie University School of Medicine, Tsu Shi, Mie Ken, Japan
    J Gen Virol 80:2017-22. 1999
    ....
  46. ncbi request reprint Interaction between nucleocapsid protein (NP) and phosphoprotein (P) of human parainfluenza virus type 2: one of the two NP binding sites on P is essential for granule formation
    M Nishio
    Department of Microbiology, Mie University School of Medicine, Tsu Shi, Japan
    J Gen Virol 77:2457-63. 1996
    ..However, cells co-expressing NP and P proteins with C-terminal deletions showed a different immunofluorescence staining pattern (diffuse pattern), indicating that the C-terminal region is required for granule formation...
  47. ncbi request reprint Microarray reveals differences in both tumors and vascular specific gene expression in de novo CD5+ and CD5- diffuse large B-cell lymphomas
    Tohru Kobayashi
    The Second Department of Internal Medicine, Mie University School of Medicine, Tsu, 514 8507, Japan
    Cancer Res 63:60-6. 2003
    ..Those results suggest that CD5(+) and CD5(-) DLBCLs have different gene expression signatures in both tumor cells and their vascular systems...
  48. ncbi request reprint Phosphorylation of CPI-17, an inhibitor of myosin phosphatase, by protein kinase N
    T Hamaguchi
    First Department of Internal Medicine, Mie University School of Medicine, Tsu, Mie, 514 8507, Japan
    Biochem Biophys Res Commun 274:825-30. 2000
    ..Thus, CPI-17 is a substrate of PKN and might be involved in the Ca(2+) sensitization of smooth muscle contraction as a downstream effector of Rho and/or arachidonic acid...
  49. ncbi request reprint Epidemiological characteristics of acute pulmonary thromboembolism in Japan
    N Yamada
    The 1st Department of Internal Medicine, Mie University, Tsu, Japan
    Int Angiol 22:50-4. 2003
    ..It is important for early diagnosis and early management of APTE to recognize epidemiological characteristics of this condition...
  50. pmc High resistance of human parainfluenza type 2 virus protein-expressing cells to the antiviral and anti-cell proliferative activities of alpha/beta interferons: cysteine-rich V-specific domain is required for high resistance to the interferons
    M Nishio
    Department of Microbiology, Mie University School of Medicine, Tsu Shi, Mie ken 514 8507, Japan
    J Virol 75:9165-76. 2001
    ..5 and 2 h in uninfected and hPIV-2-infected HeLa cells, respectively. This study shows that synthesis of Stat2 may be suppressed and Stat2 degradation is also enhanced in hPIV-2-infected HeLa and HeLa-V cells...
  51. ncbi request reprint Killing of human Herpes virus 6-infected cells by lymphocytes cultured with interleukin-2 or -12
    K Kida
    Department of Pediatrics, Mie University School of Medicine, Japan
    Pediatr Int 42:631-6. 2000
    ..The aim of present study was to investigate cytotoxicity against HHV-6-infected cells by cord blood mononuclear cells (CBMC) and adult peripheral blood mononuclear cells (PBMC)...
  52. doi request reprint Central nervous system involvement in intravascular large B-cell lymphoma: a retrospective analysis of 109 patients
    Kazuyuki Shimada
    Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
    Cancer Sci 101:1480-6. 2010
    ..Central nervous system recurrence is a serious complication in IVLBCL patients and optimal strategies for CNS involvement should be established to obtain further improvements to clinical outcomes in the rituximab era...
  53. ncbi request reprint Arachidonic acid-induced Ca2+ sensitization of smooth muscle contraction through activation of Rho-kinase
    S Araki
    First Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan
    Pflugers Arch 441:596-603. 2001
    ..The activation of Rho-kinase and subsequent phosphorylation of the myosin phosphatase target subunit inhibits myosin phosphatase and increases myosin phosphorylation...
  54. ncbi request reprint Cross-talk between RANKL and FRP-1/CD98 Systems: RANKL-mediated osteoclastogenesis is suppressed by an inhibitory anti-CD98 heavy chain mAb and CD98-mediated osteoclastogenesis is suppressed by osteoclastogenesis inhibitory factor
    K Mori
    Department of Microbiology, Mie University School of Medicine, 2-174, Edobashi, Tsu-Shi, Mie Prefecture, 514-8507, Japan
    Cell Immunol 207:118-26. 2001
    ..An inhibitory mAb directed against CD98hc, HBJ 127, shows a suppressive effect on RANKL-mediated cell aggregation and cell fusion. Thus, there is cross-talk between these two pathways...
  55. ncbi request reprint Haemostatic abnormalities and thrombotic disorders in malignant lymphoma
    Tomohiro Sase
    Second Department of Internal Medicine, Mie University School of Medicine, 2 174 Edobashi, Tsu, Mie 514 8507, Japan
    Thromb Haemost 93:153-9. 2005
    ..One of the mechanisms of DIC and IP may involve elevated cytokine production by lymphoma cells, which can stimulate the expression of TF in blood cells or surrounding tissue...
  56. ncbi request reprint Rho-associated kinase directly induces smooth muscle contraction through myosin light chain phosphorylation
    Y Kureishi
    First Department of Internal Medicine, Mie University School of Medicine, Tsu, Mie 514, Japan
    J Biol Chem 272:12257-60. 1997
    ..Our results demonstrate that Rho-kinase directly modulates smooth muscle contraction through myosin light chain phosphorylation, independently of the Ca2+-calmodulin-dependent myosin light chain kinase pathway...
  57. ncbi request reprint Involvement of ADAM9 in multinucleated giant cell formation of blood monocytes
    K Namba
    Department of Microbiology, Mie University School of Medicine, 2 174, Edobashi, Tsu Shi, Mie Prefecture, 514 8507, Japan
    Cell Immunol 213:104-13. 2001
    ..This is the first report that ADAM9 is involved in monocyte fusion, such as CD98-mediated and RANKL-mediated cell fusion of blood monocytes. Furthermore, AMAM9 is one candidate for a fusion peptide in blood monocytes...
  58. ncbi request reprint Induction of c-Src in human blood monocytes by anti-CD98/FRP-1 mAb in an Sp1-dependent fashion
    N Miyamoto
    Department of Microbiology, Department of Orthopedics, Mie University School of Medicine, 2 174, Edobashi, Tsu Shi, Mie Prefecture, 514 8507, Japan
    Cell Immunol 204:105-13. 2000
    ..Furthermore, anti-CD98HC mAb induced activation of tyrosine kinases and ERK kinases. These findings suggest that the tyrosine kinase(s)-Ras-MAPK-Sp1 pathway(s) is involved in CD98HC-mediated induction of c-Src in human blood monocytes...
  59. ncbi request reprint Circadian rhythm of blood pressure is transformed from a dipper to a non-dipper pattern in shift workers with hypertension
    T Kitamura
    The First Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan
    J Hum Hypertens 16:193-7. 2002
    ..We suggest that night shift work may have unfavourable effects on blood pressure in patients with hypertension...
  60. ncbi request reprint Gene expression during osteoclast-like cell formation induced by antifusion regulatory protein-1/CD98/4F2 monoclonal antibodies (MAbs): c-src is selectively induced by anti-FRP-1 MAb
    Y Higuchi
    Department of Microbiology, Mie University School of Medicine, Tsu Shi, Mie Prefecture, Japan
    Bone 25:17-24. 1999
    ..On the other hand, no receptor activator of NF-KB ligand (RANKL) mRNA was detectable in any of the samples, suggesting that anti-FRP-1 mAb can induce osteoclast-like cells from blood monocytes without RANKL...
  61. ncbi request reprint Effects of therapeutic doses of human atrial natriuretic peptide on load and myocardial performance in patients with congestive heart failure
    O Mizuno
    The First Department of Internal Medicine, Mie University School of Medicine, Edobashi, Japan
    Am J Cardiol 88:863-6. 2001
    ..Thus, ANP infusion increased cGMP generation, decreased afterload and preload, and improved left ventricular systolic and diastolic function...
  62. pmc Phosphorylation of myosin-binding subunit (MBS) of myosin phosphatase by Rho-kinase in vivo
    Y Kawano
    Division of Signal Transduction, Nara Institute of Science and Technology, 8916 5 Takayama, Ikoma 630 0101, Japan
    J Cell Biol 147:1023-38. 1999
    ....
  63. ncbi request reprint Regulation of myosin phosphatase by a specific interaction with cGMP- dependent protein kinase Ialpha
    H K Surks
    Molecular Cardiology Research Institute and Cardiology Division, Department of Medicine, Tufts University School of Medicine and New England Medical Center, Boston, MA 02111, USA
    Science 286:1583-7. 1999
    ..Uncoupling of the cGKIalpha-MBS interaction prevents cGMP-dependent dephosphorylation of myosin light chain, demonstrating that this interaction is essential to the regulation of vascular smooth muscle cell tone...
  64. ncbi request reprint Localization of the gene coding for myosin phosphatase, target subunit 1 (MYPT1) to human chromosome 12q15-q21
    N Takahashi
    Central Laboratories for Key Technology, Kirin Brewery Co Ltd, Kanagawa, Japan
    Genomics 44:150-2. 1997
    ..2. Radiation hybrid mapping has shown that the human MYPT1 gene is located very near the highly polymorphic marker CHLC.GATA65A12, which lies between D12S350 and D12S106...
  65. ncbi request reprint Identification and characterization of a novel protein inhibitor of type 1 protein phosphatase
    H Shirato
    Division of Biochemical Oncology and Immunology, Institute for Genetic Medicine, Hokkaido University, Kita 15, Nishi 7, Kita ku, Sapporo 060 0815, Japan
    Biochemistry 39:13848-55. 2000
    ..These results strongly suggest a multiple-point interaction between I-4 and PP1C, which is thought to cause the inhibition of I-4 which is stronger than the inhibition of I-2...
  66. ncbi request reprint Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase)
    K Kimura
    Division of Signal Transduction, Nara Institute of Science and Technology, Ikoma 630 01, Japan
    Science 273:245-8. 1996
    ..Overexpression of RhoA or activated RhoA in NIH 3T3 cells increased phosphorylation of MBS and MLC. Thus, Rho appears to inhibit myosin phosphatase through the action of Rho-kinase...
  67. ncbi request reprint Myotonic dystrophy protein kinase phosphorylates the myosin phosphatase targeting subunit and inhibits myosin phosphatase activity
    A Muranyi
    Muscle Biology Group, Shantz Building, University of Arizona, Tucson, 85721 0038, USA
    FEBS Lett 493:80-4. 2001
    ..Several approaches were taken to determine that a major site of phosphorylation was T654. Phosphorylation at T654 inhibited phosphatase activity. Thus both DMPK and Rho-kinase may regulate myosin II phosphorylation...
  68. ncbi request reprint Selected contribution: insulin utilizes NO/cGMP pathway to activate myosin phosphatase via Rho inhibition in vascular smooth muscle
    O A Sandu
    The Diabetes Research Laboratory, Winthrop University Hospital, Mineola, New York 11501, USA
    J Appl Physiol 91:1475-82. 2001
    ..Collectively, these results indicate that insulin inhibits Rho signaling by decreasing RhoA translocation via the NO/cGMP signaling pathway to cause MBP activation via site-specific dephosphorylation of its regulatory subunit MBS...
  69. ncbi request reprint Identification of the site of interaction of the 14-3-3 protein with phosphorylated tryptophan hydroxylase
    T Ichimura
    Department of Biochemistry, Faculty of Science, Niigata University, Japan
    J Biol Chem 270:28515-8. 1995
    ..The result is consistent with the recently published crystal structure of this protein family, which suggests the importance of the negatively charged groove-like structure in the ligand binding...
  70. ncbi request reprint Uncoupling proteins 2 and 3 interact with members of the 14.3.3 family
    B Pierrat
    Novartis Pharma Inc, Basle, Switzerland
    Eur J Biochem 267:2680-7. 2000
    ..3.3 proteins potentiated the inhibitory effect of UCP3 overexpression on cell growth. These findings suggest that 14.3.3 proteins could be involved in the targeting of UCPs to the mitochondria...
  71. pmc Increased B-lymphopoiesis by interleukin 7 induces bone loss in mice with intact ovarian function: similarity to estrogen deficiency
    C Miyaura
    Department of Biochemistry, School of Dentistry, Showa University, 1 5 8 Hatanodai, Shinagawa ku, Tokyo 142, Japan
    Proc Natl Acad Sci U S A 94:9360-5. 1997
    ..We propose here that the increased B-lymphopoiesis due to estrogen deficiency is involved in the mechanism of stimulated bone resorption...
  72. ncbi request reprint Nucleotide sequence of cDNA and predicted amino acid sequence of rat liver uricase
    M Ito
    Division of Molecular Genetics, Fujita Gakuen Health University, Aichi, Japan
    Eur J Biochem 173:459-63. 1988
    ..The complete amino acid sequence predicted for rat liver uricase was compared with that of soybean nodulin uricase and nine highly homologous regions of the two enzymes were found...
  73. ncbi request reprint Primary structure of the heparin-binding site of type V collagen
    Y Yaoi
    Biology Division, National Cancer Center Research Institute, Tokyo, Japan
    Biochim Biophys Acta 1035:139-45. 1990
    ..Thus this basic region is probably the heparin-binding site of type V collagen...
  74. ncbi request reprint Extended storage of granulocyte concentrates mobilized by G-CSF with/without dexamethasone and collected by bag separation method
    K Mochizuki
    Department of Pediatrics, Fukushima Medical University School of Medicine, Fukushima City, Japan
    Transfus Med 17:296-303. 2007
    ..The in vitro phagocytosis level, oxidative killing level and the viability of granulocytes mobilized by G-CSF with/without DEX and collected by bag separation method can be maintained for as long as 72 h after collection...
  75. ncbi request reprint Interaction of the ribosomal protein, L5, with protein phosphatase type 1
    K Hirano
    Muscle Biology Group, University of Arizona, Tucson 85721, USA
    J Biol Chem 270:19786-90. 1995
    ..These data indicate that L5 binds to the catalytic subunit of the type 1 protein phosphatase and may act as a target molecule for phosphatase in ribosomal function or other cell mechanisms...
  76. ncbi request reprint Antibody specific for phosphorylated AMPA-type glutamate receptors at GluR2 Ser-696
    K Nakazawa
    Laboratory for Synaptic Function, Institute of Physical and Chemical Research RIKEN, Saitama, Japan
    Neurosci Res 24:75-86. 1995
    ..This antibody may be a useful tool to study the role of AMPA receptor phosphorylation in producing synaptic plasticity...
  77. ncbi request reprint [The effect of recombinant human colony stimulating factor (G-CSF) on the function of human blood and urinary leukocytes]
    M Ito
    Department of Urology, Gifu University School of Medicine
    Kansenshogaku Zasshi 70:1140-6. 1996
    ..Therefore, urinary leukocyte activated by G-CSF and migrating from the blood through the tissue may still have its function and work in the patients with UTI...
  78. pmc DAX-1 inhibits SF-1-mediated transactivation via a carboxy-terminal domain that is deleted in adrenal hypoplasia congenita
    M Ito
    Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Medical School, Chicago, Illinois 60611, USA
    Mol Cell Biol 17:1476-83. 1997
    ..We conclude that DAX-1 can inhibit SF-1 transcriptional activity and suggest that the loss of this inhibitory property in DAX-1 may account in part for the phenotype of AHC...
  79. ncbi request reprint Negative regulation of MEKK1/2 signaling by serine-threonine kinase 38 (STK38)
    A Enomoto
    Section of Radiation Biology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo ku, Tokyo, Japan
    Oncogene 27:1930-8. 2008
    ..Taken together, our results indicate that STK38 negatively regulates the activation of MEKK1/2 by direct interaction with the catalytic domain of MEKK1/2, suggesting a novel mechanism of MEKK1/2 regulation...
  80. ncbi request reprint Identification of an amino acid residue involved in the substrate-binding site of rat liver uricase by site-directed mutagenesis
    M Ito
    Division of Molecular Genetics, Fujita Health University, School of Medicine, Aichi, Japan
    Biochem Biophys Res Commun 187:101-7. 1992
    ..These findings suggest that this amino acid is involved in the substrate-binding site of the enzyme...
  81. pmc Genetic analysis of multifocal superficial urothelial cancers by array-based comparative genomic hybridisation
    H Kawanishi
    Department of Urology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara cho, Sakyo ku, Kyoto 606 8507, Japan
    Br J Cancer 97:260-6. 2007
    ..Taken together, these findings suggest that low-grade superficial urothelial tumours accumulate minor genetic alterations during multifocal development, although these tumours are genetically stable...
  82. ncbi request reprint Reg IV is a serum biomarker for gastric cancer patients and predicts response to 5-fluorouracil-based chemotherapy
    Y Mitani
    Department of Molecular Pathology, Hiroshima University, Graduate School of Biomedical Sciences, Hiroshima, Japan
    Oncogene 26:4383-93. 2007
    ..5%) or carbohydrate antigen 19-9 (13.1%). These results indicate that expression of Reg IV is a marker for prediction of resistance to 5-FU-based chemotherapy in patients with GC. Serum Reg IV represents a novel biomarker for GC...
  83. pmc In vivo tumouricidal effects of LAD-1 monoclonal antibody on murine RL-male-1 lymphoma mediated by enhanced phagocytosis
    M Ito
    Molecular Biology and Retroviral Genetics Group, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan
    Clin Exp Immunol 141:54-61. 2005
    ..Thus, LAD-1-induced phagocytosis of lymphoma cells by hepatic macrophages in mice may, at least in part, be responsible for the prolonged survival of the mice...
  84. pmc JSAP1, a novel jun N-terminal protein kinase (JNK)-binding protein that functions as a Scaffold factor in the JNK signaling pathway
    M Ito
    Department of Biosciences, School of Science, Kitasato University, Kanagawa 228, Japan
    Mol Cell Biol 19:7539-48. 1999
    ..These results suggest that JSAP1 functions as a scaffold protein in the JNK3 cascade. We also discuss a scaffolding role for JSAP1 in the JNK1 and JNK2 cascades...
  85. ncbi request reprint Apoptosis of Neuro2a cells induced by lysosphingolipids with naturally occurring stereochemical configurations
    N Sueyoshi
    Department of Bioscience and Biotechnology, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan
    J Lipid Res 42:1197-202. 2001
    ....
  86. pmc Expression of the AT2 receptor developmentally programs extracellular signal-regulated kinase activity and influences fetal vascular growth
    M Akishita
    Cardiovascular Research, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Clin Invest 103:63-71. 1999
    ..These results suggest that the AT2 receptor expression during the fetal vasculogenesis influences the growth phenotype of VSMC via the modulation of ERK cascade...
  87. pmc mrp, a multigene, multifunctional locus in Bacillus subtilis with roles in resistance to cholate and to Na+ and in pH homeostasis
    M Ito
    Department of Biochemistry, Mount Sinai School of Medicine of the City University of New York, New York, New York 10029, USA
    J Bacteriol 181:2394-402. 1999
    ..Also, phenotypic differences among the mrp mutants suggest that functions in addition to Na+ and cholate resistance and pH homeostasis will be found among the remaining mrp genes...
  88. ncbi request reprint Development of human lymphohematopoietic stem and progenitor cells defined by expression of CD34 and CD81
    F Ma
    Divisions of Cellular Therapy and Molecular Therapy, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
    Blood 97:3755-62. 2001
    ..CD81 may serve as a marker for defining developmental stages of lymphohematopoietic stem cells. (Blood. 2001;97:3755-3762)..
  89. ncbi request reprint Mrp-dependent Na(+)/H(+) antiporters of Bacillus exhibit characteristics that are unanticipated for completely secondary active transporters
    M Ito
    Faculty of Life Scienes, Toyo University, Gunma, Japan
    FEBS Lett 496:117-20. 2001
    ..coli (SBS2115); and in increasing non-fermentative growth of an NADH dehydrogenase-minus E. coli mutant (ANN0222). The results suggest the possibility that the Mrp systems may have both secondary and primary energization capacities...
  90. ncbi request reprint A novel Jun N-terminal kinase (JNK)-binding protein that enhances the activation of JNK by MEK kinase 1 and TGF-beta-activated kinase 1
    S Koyano
    Department of Biosciences, School of Science, Kitasato University, 1 15 1 Kitasato, Kanagawa, Japan
    FEBS Lett 457:385-8. 1999
    ..In contrast, JNKBP1 had no or very little effect on the ERK signaling pathway. These results suggest that JNKBP1 functions to facilitate the specific and efficient activation of the JNK signaling pathways...
  91. pmc The interaction between the Drosophila secreted protein argos and the epidermal growth factor receptor inhibits dimerization of the receptor and binding of secreted spitz to the receptor
    M H Jin
    Division of Neuroanatomy, Department of Neuroscience, Biomedical Research Center, Osaka University Graduate School of Medicine, Osaka, Japan
    Mol Cell Biol 20:2098-107. 2000
    ..This is the first description of this novel inhibitory mechanism for receptor tyrosine kinases...
  92. ncbi request reprint Complete amino acid sequence of kaouthiagin, a novel cobra venom metalloproteinase with two disintegrin-like sequences
    M Ito
    Division of Biomedical Polymer Science, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi 470-1192, Japan
    Biochemistry 40:4503-11. 2001
    ..This is the first report of an elapid venom metalloproteinase with two disintegrin-like sequences...
  93. ncbi request reprint Urocortin and corticotropin-releasing factor receptor expression in the human colonic mucosa
    Y Muramatsu
    Department of Pathology, Tohoku University School of Medicine, 2 1 Seiryo machi, Aoba ku, Sendai 980 8575, Japan
    Peptides 21:1799-809. 2000
    ..The appearance of urocortin after birth indicates that the exposure to dietary intake and/or luminal bacteria after birth may contribute to the initiation of urocortin expression in human gastrointestinal tract mucosa...
  94. ncbi request reprint Isoforms of JSAP1 scaffold protein generated through alternative splicing
    M Ito
    Department of Biosciences, School of Science, Kitasato University, Sagamihara, 228 8555, Kanagawa, Japan
    Gene 255:229-34. 2000
    ..These results suggest that JSAP1c and JSAP1d may attenuate the scaffolding activity of JSAP1a and/or JSAP1b in JNK cascades, especially the JNK3 cascades...
  95. pmc Molecular events involved in up-regulating human Na+-independent neutral amino acid transporter LAT1 during T-cell activation
    T Nii
    Department of Clinical Nutrition, School of Medicine, Tokushima University, Kuramoto Cho 3, Tokushima City 770 8503, Japan
    Biochem J 358:693-704. 2001
    ..These findings indicated that a removal of the block to mRNA elongation stimulates the induction of system-L amino acid transporter gene transcripts (LAT1 and 4F2hc) in activated T-cells...
  96. pmc Tyrosine phosphorylation sites on FRS2alpha responsible for Shp2 recruitment are critical for induction of lens and retina
    N Gotoh
    Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA
    Proc Natl Acad Sci U S A 101:17144-9. 2004
    ..These experiments demonstrate that intracellular signals that depend on specific tyrosine residues in FRS2alpha lie upstream of gene products critical for induction of lens and retina...
  97. ncbi request reprint cDNA cloning of a novel rainbow trout SRY-type HMG box protein, rtSox23, and its functional analysis
    A Yamashita
    Department of Biosciences, School of Science, Kitasato University, 1 15 1 Kitasato, Sagamihara, Kanagawa 228, Japan
    Gene 209:193-200. 1998
    ..The rainbow trout p62 mRNA was also prominent in ovary and brain. Taken together, these results suggest that the rainbow trout p62 associates with rtSox23 in vivo and modulates the function of rtSox23...
  98. pmc Polarity of helper T cell subsets represents disease nature and clinical course of experimental autoimmune myocarditis in rats
    K Fuse
    Division of Cardiology and Division of Haematology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
    Clin Exp Immunol 134:403-8. 2003
    ..Thus, analysis of Th1/Th2 balance in peripheral T cells may be useful in disease monitoring in patients with myocarditis and postmyocarditic dilated cardiomyopathy...
  99. ncbi request reprint Prognostic factors in resection of pulmonary metastasis from colorectal cancer
    I Watanabe
    Surgery Division, National Cancer Center Hospital East, 6 5 1 Kashiwanoha, Kashiwa, Chiba 277 8577, Japan
    Br J Surg 90:1436-40. 2003
    ....
  100. ncbi request reprint A novel gene, GliH1, with homology to the Gli zinc finger domain not required for mouse development
    M Nakashima
    Department of Clinical Oral Molecular Biology, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka 812 8582, Japan
    Mech Dev 119:21-34. 2002
    ....
  101. ncbi request reprint Characterization of Solt, a novel SoxLZ/Sox6 binding protein expressed in adult mouse testis
    A Yamashita
    Department of Biosciences, School of Science, Kitasato University, 1 15 1 Kitasato, Sagamihara, 228, Kanagawa, Japan
    FEBS Lett 481:147-51. 2000
    ....