Faculty Profiles - FUJII Nobuharu

MISC - FUJII Nobuharu

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発熱で発症し診断に苦慮したIVLの一例

杉山暖子, 前田嘉信, 田淵貴大, 西森久和, 山筋好子, 藤井伸治, 品川克至, 石丸文彦, 池田和真, 谷本光音

日本リンパ網内系学会会誌 46 76 - 76 2006.6

進行期低悪性度リンパ腫に対する骨髄非破壊的同種造血幹細胞移植

久保西四郎, 田淵貴大, 山筋好子, 杉山暖子, 西森久和, 藤井伸治, 前田嘉信, 品川克至, 石丸文彦, 池田和真, 谷本光音

日本リンパ網内系学会会誌 46 100 - 100 2006.6

Hodgkin/Reed-Sternberg様細胞を散在性に認めるLymphoplasmacytic lymphomaの一例

小山幹子, 品川克至, 青山一利, 増成太郎, 近藤英生, 藤井伸治, 豊嶋崇徳, 石丸文彦, 池田和真, 谷本光音, 佐藤由美子, 市村浩一, 吉野正

日本リンパ網内系学会会誌 44 129 - 129 2004.6

8.自己末梢血幹細胞至適採取時期決定における末梢血CIC countの有効性に関する検討(一般演題)(日本アフェレシス学会第22回関西地方会抄録)

吉田親正, 池田和真, 小塚輝彦, 久保西四郎, 小出典男, 豊嶋崇徳, 藤井伸治, 品川克至, 石丸文彦, 谷本光音

日本アフェレシス学会雑誌 23 ( 2 ) 207 - 207 2004

Peripheral blood circulating immature cell counts predict CD34+cell yields in granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cell collection in healthy donors.

K Ikeda, T Kozuka, T Teshima, C Yoshida, S Kubonishi, K Sunami, K Matsuo, K Masuda, N Fujii, K Takenaka, K Shinagawa, F Ishimaru, N Koide, M Harada, M Tanimoto

BLOOD 102 ( 11 ) 414B - 414B 2003.11

Multilineage involvement in hypereosinophilic syndrome terminating in granulocytic sarcoma and leukaemic transformation with trisomy 8

N Fujii, K Ikeda, N Takahashi, K Kojima, Y Kobayashi, A Ashiba, K Takenaka, S Fukuda, K Shinagawa, F Ishimaru, K Niiya, Miura, I, M Tanimoto, M Harada

BRITISH JOURNAL OF HAEMATOLOGY 119 ( 3 ) 716 - 719 2002.12

Language：English Publisher：BLACKWELL PUBLISHING LTD

We report a patient with hypereosinophilic syndrome (HES), which, 8 years later, transformed into granulocytic sarcoma in the brain and, subsequently, into acute myelocytic leukaemia. Repeated chromosome analyses showed a normal karyotype, until the time of leukaemic transformation when trisomy 8 was confirmed in cells from the bone marrow and cerebrospinal fluid. The combined techniques of May-Grunwald-Giemsa staining and fluorescence in situ hybridization identified trisomy 8 not only in blasts and eosinophils but also in neutrophils and erythroblasts. Our observation suggests that HES is a multilineage myeloproliferative disorder involving precursors of at least the eosinophil, neutrophil and erythroid lineages.

DOI： 10.1046/j.1365-2141.2002.03922.x

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Allografting of peripheral blood stem cell mobilized from a donor developing herpes zoster virus infection [5]

Toshi Imai, Yoshinobu Maeda, Nobuharu Fujii, Katsuto Takenaka, Katsuji Shinagawa, Fumihito Ishimaru, Kazuma Ikeda, Kenji Niiya, Mine Harada

American Journal of Hematology 71 ( 2 ) 140 - 141 2002.10

Differentiation of monoblastic cell line UG3 into leukemic dendritic cells

N Fujii, T Ikeda, K Ikeda, A Hiraki, K Kawakami, K Masuda, Y Maeda, K Hatake, K Motoyoshi, M Harada, M Tanimoto

INTERNATIONAL JOURNAL OF ONCOLOGY 21 ( 3 ) 617 - 620 2002.9

Language：English Publisher：PROFESSOR D A SPANDIDOS

Dendritic cells (DCs) are known to be generated from leukemic clone from patients with acute and chronic leukemia when cultured in the presence of combination of granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF-alpha) and interleukin-4. However, there have been few reports that showed DCs could be effectively differentiated from human leukemia cell lines. In this study, we have shown that a human monoblastic cell line, UG3, was inducible to differentiate into DCs in the presence of GM-CSF and TNF-alpha along monocyte-macrophage lineage. These DCs, consistently displayed dendritic morphology, phenotypes and allogeneic T-cell stimulating capacity. UG3 cells thus may represent a suitable model to further elucidate characteristics of DC differentiation.

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Successful Treatment of Progressive NK Cell Lymphoma with Allogeneic Peripheral Stem Cell Transplantation Followed by Early Cyclosporine Tapering and Donor Leukocyte Infusions

MAKITA Masanori, MAEDA Yoshinobu, TAKENAKA Katsuto, SHINAGAWA Katsuji, SUNAMI Kazutaka, HIRAMATSU Yasushi, FUJII Nobuharu, ISHIMARU Fumihiko, IKEDA Kazuma, NIIYA Kenji, YOSHINO Tadashi, HARADA Mine

Int J Hematol 76 ( 1 ) 94 - 97 2002.7

Expression of minor histocompatibility antigen, HA-1, in solid tumor cells

N Fujii, A Hiraki, K Ikeda, Y Ohmura, Nozaki, I, K Shinagawa, F Ishimaru, K Kiura, N Shimizu, M Tanimoto, M Harada

TRANSPLANTATION 73 ( 7 ) 1137 - 1141 2002.4

Language：English Publisher：LIPPINCOTT WILLIAMS & WILKINS

Background. Minor histocompatibility antigen (mHag) induces and mounts graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Among several mHags, HA-1 is one that acts alone and is the most studied. It is suggested that HA-1 may be one of the immunodominant antigens inducing not only graft-versus-host disease but also graft-versus-malignancy effects. There are some reports that mHag HA-1-specific cytotoxic T lymphocytes generated from an HA-1-negative donor can lyse HA-1-positive leukemic cells. However, the tissue distribution of HA-1 has been described as restricted to the cells of the hematopoietic lineage.
Methods. We examined the HA-1 expression in peripheral blood mononuclear cells (PBMNC), leukemia/lymphoma cell lines, solid tumor cell lines, and paired samples of tumor and normal tissues from individual cancer patients by quantitative reverse-transcription polymerase chain reaction.
Results. We found that mRNA of HA-1 is expressed in all leukemia/lymphoma cell lines and PBMNC. Most of the leukemia/lymphoma cell lines have the same levels of HA-1 expression as a leukemia/lymphoma cell line, Raji. The expression levels of human PBMNC were 14- to 19-fold higher than those of Raji. Among 32 solid tumor cell lines, 7 showed >50% expression levels compared with Raji.
Conclusions. HA-1 expression in the mRNA level is higher in cells of hematopoietic origin, but this tissue distribution is not strictly restricted. Some solid tumor cells and tissues express HA-1 gene equal to hematopoietic cells.

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Differentiation of monoblastic cell line UG3 into leukemic dendritic cells.

Fujii N, Ikeda T, Ikeda K, Hiraki A, Kawakami K, Masuda K, Maeda Y, Hatake K, Motoyoshi K, Harada M, Tanimoto M.

Int J Oncol. 21 ( 3 ) 617 2002

Expression of minor histocompatibility antigen, HA-1, in solid tumor cells. International journal

Nobuharu Fujii, Akio Hiraki, Kazuma Ikeda, Yasushi Ohmura, Isao Nozaki, Katsuji Shinagawa, Fumihiko Ishimaru, Katsuyuki Kiura, Nobuyoshi Shimizu, Mitsune Tanimoto, Mine Harada

Transplantation 73 ( 7 ) 1137 - 41 2002

Language：English

BACKGROUND: Minor histocompatibility antigen (mHag) induces and mounts graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Among several mHags, HA-1 is one that acts alone and is the most studied. It is suggested that HA-1 may be one of the immunodominant antigens inducing not only graft-versus-host disease but also graft-versus-malignancy effects. There are some reports that mHag HA-1-specific cytotoxic T lymphocytes generated from an HA-1-negative donor can lyse HA-1-positive leukemic cells. However, the tissue distribution of HA-1 has been described as restricted to the cells of the hematopoietic lineage. METHODS: We examined the HA-1 expression in peripheral blood mononuclear cells (PBMNC), leukemia/lymphoma cell lines, solid tumor cell lines, and paired samples of tumor and normal tissues from individual cancer patients by quantitative reverse-transcription polymerase chain reaction. RESULTS: We found that mRNA of HA-1 is expressed in all leukemia/lymphoma cell lines and PBMNC. Most of the leukemia/lymphoma cell lines have the same levels of HA-1 expression as a leukemia/lymphoma cell line, Raji. The expression levels of human PBMNC were 14- to 19-fold higher than those of Raji. Among 32 solid tumor cell lines, 7 showed >50% expression levels compared with Raji. CONCLUSIONS: HA-1 expression in the mRNA level is higher in cells of hematopoietic origin, but this tissue distribution is not strictly restricted. Some solid tumor cells and tissues express HA-1 gene equal to hematopoietic cells.

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Multilineage involvement on hypereosinophilic symdrome terminating in granulocytic sarcoma and leukaemic transformation with trisomy 8.

Br J Haematol. 119 ( 3 ) 716 2002

GM-CSF and TNF-alpha induce monoblastic line UG3 to differentiate into dendritic cells.

K Masuda, N Fujii, K Ikeda, A Hiraki, T Ikeda, K Kawakami, M Harada, M Tanimoto

BLOOD 98 ( 11 ) 228A - 229A 2001.11

High-dose chemotherapy with hematopoietic stem cell transplantation is effective for nasal and nasal-type CD56(+) natural killer cell lymphomas

K Takenaka, K Shinagawa, Y Maeda, M Makita, T Kozuka, A Ashiba, K Yamamoto, N Fujii, Y Nawa, Y Hiramatsu, K Sunami, F Ishimaru, T Yoshimo, K Kiura, M Harada

LEUKEMIA & LYMPHOMA 42 ( 6 ) 1297 - 1303 2001.11

Language：English Publisher：TAYLOR & FRANCIS LTD

CD56(+) natural killer (NK) cell lymphomas occur frequently in the nasal and nasopharyngeal regions and carry a poor prognosis. We have studied seven cases with NK-cell lymphomas. These lymphomas showed the following immunophenotype: CD56(+), CD2(+), sCD3(-) and Epstein-Barr virus-encoded small RNAs (EBERs)(+). Six patients had localized (stage I or II) disease involving the nasopharyngeal region, while one had stage III disease. One patient with stage I disease achieved a complete remission (CR) after treatment with involved-field irradiation, but subsequently relapsed and died. The remaining six patients received combination chemotherapy as primary treatment: five patients with localized stage I or II disease and one patient with advanced stage III disease. Responses to initial chemotherapy were generally poor. These six patients received a variety of salvage chemotherapy regimens, but never achieved a CR. Subsequently, four of six patients showed a highly aggressive clinical course and died of disseminated disease within 1 year from the diagnosis. Three of six patients received high-dose chemotherapy supported by syngeneic, autologous or allogeneic peripheral blood stem cell transplantation. Two of the three transplant patients achieved a CR and are now surviving in continuous CR. Our clinical experience suggests that myeloablative high-dose chemotherapy and bone marrow rescue by hematopoietic stem cell transplantation may be an effective salvage treatment modality for refractory NK-cell lymphomas and could be considered as a part of the initial therapy for these patients.

DOI： 10.1080/10428190127500

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Hepatic graft-versus-host disease presenting as an acute hepatitis after allogeneic peripheral blood stem cell transplantation

N Fujii, K Takenaka, K Shinagawa, K Ikeda, Y Maeda, K Sunami, Y Hiramatsu, K Matsuo, F Ishimaru, K Niiya, T Yoshino, N Hirabayashi, M Harada

BONE MARROW TRANSPLANTATION 27 ( 9 ) 1007 - 1010 2001.5

Language：English Publisher：NATURE PUBLISHING GROUP

Hepatic graft-versus-host disease (GVHD) generally presents as cholestatic jaundice, and increased serum alkaline phosphatase (ALP) is followed by hyperbilirubinemia and clinical jaundice. Currently accepted standards for evaluating the clinical severity of GVHD are based not on serum aminotransferase levels but on the serum bilirubin level. We describe a 17-year-old Japanese female who had increased aminotransferases without cholestasis on day 23 after allogeneic peripheral blood stem cell transplantation (allo-PBSCT), Liver biopsy revealed lymphocytic infiltration of the portal tracts and pericentral necrosis of the lobuli, The limiting plates were not clearly defined due to cellular infiltrates. There was periductal lymphocytic infiltration and vacuolization of the biliary epithelial cells with exocytosis, compatible with GVHD of cholangiohepatitic type. These findings indicate that acute hepatic GVHD may present as acute hepatitis and this should be included in the differential diagnosis for patients with increased aminotransferases after allogeneic stem cell transplantation.

DOI： 10.1038/sj.bmt.1702997

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Lamivudine and glycyrrhizin for treatment of chemotherapy-induced hepatitis B virus (HBV) hepatitis in a chronic HBV carrier with non-Hodgkin lymphoma

K Matsuo, K Takenaka, H Shimomura, N Fujii, K Shinagawa, K Kiura, M Harada

LEUKEMIA & LYMPHOMA 41 ( 1-2 ) 191 - 195 2001.3

Language：English Publisher：HARWOOD ACAD PUBL GMBH

We report a chronic hepatitis B virus (HBV) carrier with non-Hodgkin lymphoma (NHL) who developed HBV hepatitis following conventional dose chemotherapy and was successfully treated with lamivudine and glycyrrhizin. A 55 year-old male patient with primary testicular NHL (diffuse large B-cell type) relapsed. During the salvage chemotherapy, the patient showed elevated serum levels of transaminase and HBV-DNA due to HBV reactivation. Treatment with lamivudine. an antiviral nucleoside analog, was started at a dose of 100mg/day. Shortly after the treatment the HBV-DNA level was suppressed, and sustained elevation of transaminase levels were normalized after additional treatment with glycyrrhizin. This experience suggests that lamivudine combined with glycyrrhizin may be effective:e for controlling HBV replication and treating chemotherapy-induced HBV hepatitis in chronic HBV carriers with NHL.

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Hepatic graft-versus-host disease presenting as acute hepatitis after allogeneic peripheral blood stem cell transplantation

FUJII N

Bone Marrow Transplant 27 ( 9 ) 1007 - 1010 2001

G-CSF投与健常人ドナーからの末梢血幹細胞採取の経験(一般演題,日本アフェレシス学会第19回関西地方会抄録)

今井利, 小塚輝彦, 山本和彦, 藤井伸治, 前田嘉信, 中克斗, 品川克至, 池田和真, 原田実根, 角南一貴

日本アフェレシス学会雑誌 20 ( 1 ) 118 - 118 2001

Successful engraftment of allogeneic peripheral blood stem cell transplant after nonmyeloablative preparative regimen with cytarabine and cyclophosphamide: Report of 2 cases

N Fujii, Y Maeda, K Takenaka, K Shinagawa, T Imai, T Kozuka, K Ikeda, K Sunami, Y Hiramatsu, F Ishimaru, K Niiya, M Harada

INTERNATIONAL JOURNAL OF HEMATOLOGY 72 ( 4 ) 499 - 503 2000.12

Language：English Publisher：CARDEN JENNINGS PUBL CO LTD

We report our experience with allogeneic peripheral blood stem cell transplantation (allo-PBSCT) following a nonmyeloablative conditioning regimen consisting of cytarabine (8 g/m(2)) and cyclophosphamide (120 mg/kg) in the treatment of 2 patients aged 50 and 55 years with refractory chronic myelomonocytic leukemia and chronic myeloid leukemia in accelerated phase, respectively. Our nonmyeloablative regimen was well tolerated by older patients at high risk of regimen-related toxicity by the conventional conditioning regimen but was immunosuppressive enough to achieve mixed chimerism. After allo-PBSCT, we monitored chimerism in these patients by fluorescence in situ hybridization using X- and Y-specific probes and polymerase chain reaction-based analysis of a variable number of tandem repeats. We found that full chimerism and graft-versus-leukemia (GVL) effects could be induced in these patients by donor lymphocyte infusions and withdrawal of post transplantation immunosuppressive therapy. Our observations suggest that a nonmyeloablative conditioning regimen can establish mixed chimerism and that donor lymphocyte infusion may induce GVL effects in older patients at high risk of regimen-related toxicity. Int J Hematol. 2000;72:499-503. (C)2000 The Japanese Society of Hematology.

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