論文 - 村瀬　和幸

A case of ulcerative colitis accompanied with myelodysplastic syndrome successfully treated by cyclosporine

Sho Takahashi, Yasushi Sato, Tamotsu Sagawa, Shingo Tanaka, Kazuyuki Murase, Kohichi Takada, Satoshi Iyama, Tsutomu Sato, Rishu Takimoto, Masayoshi Kobune, Ganji Kuroiwa, Michiaki Hirayama, Tetsuro Okamoto, Junji Kato

Journal of Japanese Society of Gastroenterology ( 8 )  108 ( 8 ) 1405 - 1412  2011年08月  [査読有り]

　概要を見る

A 64-year-old man had been admitted to a previous hospital because of melena and a diagnosis of ulcerative colitis (UC, pancolitis type) had been made. He had received prednisolone and 5-ASA but steroid-induced hyperamylasemia had developed. Prednisolone had been tapered and halted, but it had resulted in UC relapse and thrombocytopenia. Then, he was referred to our hospital due to severe melena with hypovolemic shock. However, he was also positive for CMV antigen. Thus, we attempted to treat him with ganciclovir for CMV and intravenous cyclosporine (CsA) for UC. According to his clinical course, a reduction of CsA blood concentration induced leukocytopenia. Myelodysplastic syndrome (MDS, RAEB-1) was then revealed after bone marrow biopsy. A high blood CsA concentration may cause the improvement of UC and MDS conditions.

DOI PubMed

Iron chelator deferasirox rescued mice from Fas-induced fulminant hepatitis

Tsutomu Sato, Masayoshi Kobune, Kazuyuki Murase, Yukari Kado, Tetsuro Okamoto, Shingo Tanaka, Shohei Kikuchi, Hiroyuki Nagashima, Yutaka Kawano, Kohichi Takada, Satoshi Iyama, Koji Miyanishi, Yasushi Sato, Rishu Takimoto, Junji Kato

HEPATOLOGY RESEARCH ( WILEY-BLACKWELL )  41 ( 7 ) 660 - 667  2011年07月  [査読有り]

　概要を見る

Aim: Fulminant hepatitis is a disease characterized by development of hepatic failure due to severe liver cell injury. Orthotopic liver transplantation is the therapy proven to improve patient survival; however, less burdensome and safer strategies are required. In a previous study, we showed that iron was intimately involved in hepatocyte apoptosis by demonstrating that spontaneous development of fulminant hepatitis in Long-Evans cinnamon rats was prevented by feeding an iron-deficient diet. Recently, a new iron chelator, deferasirox, has become widely available for the treatment of transfusional hemosiderosis. Deferasirox demonstrated good efficacy and improved compliance due to convenient, once-daily p.o. administration. Our aim was to investigate the efficacy of deferasirox as a therapeutic drug against fulminant hepatitis. Methods: Human primary hepatocytes undergoing Fas-stimulated apoptosis were challenged with deferoxamine (DFO) in vitro. In further in vivo experiments, we tested DFO in a mice model of fulminant hepatitis induced by Fas-stimulation. Results: The apoptosis-inducing activity of anti-Fas antibody on human primary hepatocytes was inhibited by the chelation of iron with DFO. DFO suppressed the Fas-induced production of reactive oxygen species (ROS) and the activation of caspase-3, both of which were also suppressed by antioxidant, N-acetyl-L-cystein. In the in vivo experiments, deferasirox effectively reduced hepatic iron concentrations and rescued mice from Fas-induced fulminant hepatitis. Conclusion: These findings indicated that the iron chelation exerted a hepatoprotective effect by scavenging ROS upstream of caspase-3 and that iron chelation with deferasirox is a potential treatment for patients with fulminant hepatitis.

DOI PubMed

Novel missense mutation in the TMPRSS6 gene in a Japanese female with iron-refractory iron deficiency anemia

Tsutomu Sato, Satoshi Iyama, Kazuyuki Murase, Yusuke Kamihara, Kaoru Ono, Shohei Kikuchi, Kohichi Takada, Koji Miyanishi, Yasushi Sato, Rishu Takimoto, Masayoshi Kobune, Junji Kato

INTERNATIONAL JOURNAL OF HEMATOLOGY ( SPRINGER TOKYO )  94 ( 1 ) 101 - 103  2011年07月  [査読有り]

　概要を見る

Iron-refractory iron deficiency anemia (IRIDA) is a rare autosomal-recessive disorder hallmarked by hypochromic microcytic anemia, low transferrin saturation, and unresponsiveness to oral iron with partial recovery after parenteral iron administration. The disease is caused by mutations in TMPRSS6 (transmembrane protease serine 6) that prevent inactivation of membrane-bound hemojuvelin, an activator of hepcidin transcription. To date, 38 cases have been characterized and reported in European countries and the United States. In this paper, we describe the first case of a Japanese female with IRIDA, who carried a novel mutation (K253E) in the CUB (complement factor C1r/C1s, urchin embryonic growth factor and bone morphogenetic protein 1) domain of the TMPRSS6 gene.

DOI PubMed

Establishment of a simple test for iron absorption from the gastrointestinal tract

Masayoshi Kobune, Koji Miyanishi, Kohichi Takada, Yutaka Kawano, Hiroyuki Nagashima, Shohei Kikuchi, Kazuyuki Murase, Satoshi Iyama, Tsutomu Sato, Yasushi Sato, Rishu Takimoto, Junji Kato

INTERNATIONAL JOURNAL OF HEMATOLOGY ( SPRINGER TOKYO )  93 ( 6 ) 715 - 719  2011年06月  [査読有り]

　概要を見る

Recent studies on iron metabolism have begun to reveal the molecular mechanisms underlying iron absorption, which is dramatically affected in several disorders. In the clinical setting, the ability to determine the status of iron absorption would aid in the diagnosis of pathological conditions. Efforts to develop an oral iron absorption test (OIAT) date back to at least 60 years. However, previous procedures were associated with a number of problems, such as radiation exposure and low reproducibility. In an attempt to resolve these issues, we employed sodium ferrous citrate (SFC), by which the influence of various nutrients and drugs on iron absorption was markedly reduced. We found that OIAT using SFC was simple to perform in both hospitalized patients and outpatients. The increment of serum iron and % transferrin saturation at 120 min after SFC administration was useful in distinguishing iron absorption between healthy volunteers, patients with iron-deficiency anemia, and patients with anemia secondary to chronic disorders, which are respectively characterized by normal, enhanced, and reduced iron absorption. Thus, the SFC-based OIAT may represent a viable screening test for the evaluation of gastrointestinal iron absorption.

DOI PubMed

Tuberculous pleuritis with onset of refractory pleural effusion after chemoradiotherapy for esophageal cancer

Masahiro Hirakawa, Yasushi Sato, Hiroyuki Ohnuma, Tamotsu Sagawa, Hirotoshi Ishiwatari, Kazuyuki Murase, Satoshi Iyama, Tsuyoshi Hayashi, Tsutomu Sato, Koji Miyanishi, Masayoshi Kobune, Rishu Takimoto, Junji Kato

Journal of Japanese Society of Gastroenterology ( 2 )  108 ( 2 ) 231 - 237  2011年02月  [査読有り]

　概要を見る

A 75-year-old man received chemoradiotherapy (CRT) for stage IVa esophageal cancer and complete response (CR) was obtained. However, he was referred to our department for recurrence in an area of esophagus not included in the previously irradiated field. Left pleural effusion increased after admission. Tuberculous pleuritis was eventually diagnosed by thoracoscopic pleural biopsy. It is necessary to accurately diagnose the cause of pleural effusion after CRT, because treatment strategies greatly depend on it. It is also necessary to consider the possible onset of tuberculous pleuritis, in particular, in patients with a history of tuberculosis infection.

DOI PubMed

ENDOSCOPIC FINDINGS OF ENTEROPATHY-TYPE T-CELL LYMPHOMA BY DOUBLE-BALLOON ENTEROSCOPY AND CAPSULE ENDOSCOPY

Yasushi Sato, Michihiro Ono, Tamotsu Sagawa, Rishu Takimoto, Masahiro Hirakawa, Hiroyuki Ohnuma, Tsutomu Sato, Satoshi Iyama, Kazuyuki Murase, Koji Miyanishi, Masayoshi Kobune, Junji Kato

DIGESTIVE ENDOSCOPY ( WILEY-BLACKWELL )  22 ( 3 ) 243 - 245  2010年07月  [査読有り]

　概要を見る

Enteropathy-type T-cell lymphoma (ETL) is a rare primary intestinal disorder, particularly in Japan, and there have been few reports on the endoscopic findings of the disease. Here we report detailed endoscopic findings of ETL based on double-balloon enteroscopy and capsule endoscopy. Double-balloon enteroscopy and capsule endoscopy may be useful tools for diagnosing and monitoring the effects of therapy in patients with ETL.

DOI PubMed

Therapeutic results in patients with biphenotypic acute leukemia at Sapporo Medical University Hospital

Kazuyuki Murase, Satoshi Iyama, Tsutomu Sato, Rishu Takimoto, Masayoshi Kobune, Junji Kato

Japanese Journal of Cancer and Chemotherapy ( Japanese Journal of Cancer and Chemotherapy Publishers Inc. )  37 ( 10 ) 2011 - 2013  2010年  [査読有り]

　概要を見る

We reviewed the results of 6 patients with biphenotypic acute leukemia (BAL) which the diagnostic standard of the European Group for the Immunological Characterization of Leukemia (EGIL) at Sapporo Medical University Hospital between 2006 and 2008. There were 5 males and 1 females with an average age of 35 years. Among them, 4 were B lymphoid and myeloid, 2 were T lymphoid and myeloid, and one was T/B lymphoid. Two of 4 patients did not attain complete remission, and two relapsed after first treatment with acute myeloblastic leukemia (AML) protocol. On the other hand, two showed complete remission after the acute lymphoblastic leukemia (ALL) protocol. One of 4 patients survived who had been treated with hematopoietic stem cell transplantation as a post-remission therapy. The ALL protocol was good for the induction therapy. However, overall treatment-related deaths were 4 patients and considerable caution was necessary.

PubMed

Treatment of Cirrhosis with Vitamin A-Coupled Liposomes Carrying siRNA against Heat Shock Protein

Yoshiro Niitsu, Yasushi Sato, Kazuyuki Murase, Junji Kato

The Liver: Biology and Pathobiology: Fifth Edition ( John Wiley & Sons, Ltd. )    1121 - 1129  2009年10月  [査読有り]

DOI

ヘッジホッグ・シグナル伝達阻害剤は、CD34+白血病細胞の薬剤耐性を解除する

菊地 尚平, 小船 雅義, 村瀬 和幸, 井山 諭, 佐藤 勉, 瀧本 理修, 河野 豊, 宮西 浩嗣, 佐藤 康史, 加藤 淳二

臨床血液 ( (一社)日本血液学会-東京事務局 )  50 ( 9 ) 1113 - 1113  2009年09月  [査読有り]

シクロパミンは、CD34陽性白血病細胞の薬剤耐性を解除する(Cyclopamine dramatically restores drug resistance of CD34+ leukemic cells)

小船 雅義, 井山 諭, 佐藤 勉, 瀧本 理修, 菊地 尚平, 村瀬 和幸, 河野 豊, 宮西 浩嗣, 佐藤 康史, 加藤 淳二

日本癌学会総会記事 ( 日本癌学会 )  68回   480 - 480  2009年08月  [査読有り]

Drug resistance is dramatically restored by hedgehog inhibitors in CD34(+) leukemic cells

Masayoshi Kobune, Rishu Takimoto, Kazuyuki Murase, Satoshi Iyama, Tsutomu Sato, Shohei Kikuchi, Yutaka Kawano, Kohji Miyanishi, Yasushi Sato, Yoshiro Niitsu, Junji Kato

CANCER SCIENCE ( WILEY-BLACKWELL )  100 ( 5 ) 948 - 955  2009年05月  [査読有り]

　概要を見る

Aberrant reactivation of hedgehog (Hh) signaling has been described in a wide variety of human cancers and in cancer stem cells. However, the contribution of Hh signaling to leukemic cell regulation has remained unclear. In this study, we assessed the possibility that Hh pathway activation contributes to the survival and drug resistance of cluster of differentiation (CD)34(+) leukemia cells. Hh signaling in leukemic cell lines and primary leukemic cells was screened by reverse transcription - polymerase chain reaction (RT-PCR) and a Hh signaling reporter assay. We found that Hh signaling is active in several human acute myeloid leukemia (AML) cells, especially primary CD34(+) leukemic cells and cytokine-responsive CD34+ cell lines such as Kasumi-1, Kasumi-3 and TF-1. These CD34+ cells express the downstream effectors glioma-associated oncogene homolog (GLI)1 or GLI2, indicative of active Hh signaling. Moreover, inhibition of Hh signaling with the naturally derived Smoothened antagonist cyclopamine, endogenous Hh inhibitor hedgehog-interacting protein or anti-hedgehog neutralizing antibody induced apoptosis after 48 h of exposure, although these CD34(+) cell lines exhibited resistance to cytarabine (Ara-C). In contrast, cyclopamine failed to affect growth or survival in U937 and HL-60 cell lines that lack expression of Hh receptor components, confirming that the effect of Hh inhibition is specific. Furthermore, combination with 10 mu M cyclopamine significantly reduced drug resistance of CD34(+) cell lines and primary CD34(+) leukemic cells to Ara-C. These results suggest that aberrant Hh pathway activation is a feature of some CD34(+) myeloid leukemic cells and Hh inhibitors may have a therapeutic role in the treatment of AML. (Cancer Sci 2009; 100: 948-955).

DOI PubMed

ヒト骨髄間質細胞は臍帯血CD34陰性細胞のCXCR4発現増強と長期造血再建能を誘導する

小船 雅義, 村瀬 和幸, 井山 諭, 佐藤 勉, 河野 豊, 瀧本 理修, 松永 卓也, 加藤 淳二

臨床血液 ( (一社)日本血液学会-東京事務局 )  49 ( 9 ) 940 - 940  2008年09月  [査読有り]

[A case of hepatosplenic gammadelta T-cell lymphoma associated hemophagocytic syndrome].

Iyama S, Matsunaga T, Sato T, Sato Y, Sagawa T, Murase K, Kida M, Kobune M, Takimoto R, Kato J, Niitsu Y

Gan to kagaku ryoho. Cancer & chemotherapy ( 9 )  35 ( 9 ) 1623 - 1627  2008年09月  [査読有り]

PubMed

Interaction with human stromal cells enhances CXCR4 expression and engraftment of cord blood Lin(-)CD34(-) cells

Masayoshi Kobune, Yutaka Kawano, Sho Takahashi, Kohichi Takada, Kazuyuki Murase, Satosi Iyama, Tsutomu Sato, Rishu Takimoto, Yoshiro Niitsu, Junji Kato

EXPERIMENTAL HEMATOLOGY ( ELSEVIER SCIENCE INC )  36 ( 9 ) 1121 - 1131  2008年09月  [査読有り]

　概要を見る

Objective. Transplantation of hematopoietic stem cells (HSCs) is usually accomplished through intravenous injection, a complex process that requires recognition of bone marrow vasculature and migration to a supportive microenvironment. Hence, some populations of HSCs, including cord blood (CB) Lin(-)CD34(-) stem cells, do not engraft well in bone marrow (BM) of nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. In this study, we examined the effect of human stromal interactions on the properties of CB Lin(-)CD34(-) cells. Materials and Methods. CD34 and CXCR4 expression on fresh CB Lin(-)CD34(-) cells and CB Lin(-)CD34(-) cells cocultured with human stromal cells were analyzed. Homing activity and engraftment of these cells were assessed using NOD/SCID mice. In an attempt to identify the stromal CXCR4-inducing factor, CB Lin(-)CD34(-) cells were cocultured with a noncontact culture system in the presence of several inhibitors. Result. Coculture with human stromal cells induced expression of CD34 and CXCR4 on CB Lin(-)CD34(-) cells. CXCR4 expression on CB Lin(-)CD34(-) cells was induced even in the noncontact culture condition, suggesting that this CXCR4-inducing factor is soluble. Moreover, CXCR4 induction was inhibited by the soluble Wnt inhibitor DKK1. Furthermore, these cells acquired homing activity and engrafted in the BM of NOD/SCID mice after intravenous injection. Conclusion. These findings maybe useful for understanding the role of stromal cells in homing and engraftment of HSCs. (C) 2008 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.

DOI PubMed

アデノウイルスベクターを用いたヘッジホッグ遺伝子の高発現は、TおよびBリンパ球の分化抑制を誘導する

加藤 淳二, 小船 雅義, 村瀬 和幸, 井山 諭, 佐藤 勉, 河野 豊, 瀧本 理修, 松永 卓也

臨床血液 ( (一社)日本血液学会-東京事務局 )  49 ( 9 ) 1085 - 1085  2008年09月  [査読有り]

Apoptosis supercedes necrosis in mitochondrial DNA-depleted Jurkat cells by cleavage of receptor-interacting protein and inhibition of lysosomal cathepsin.

Sato T, Machida T, Takahashi S, Murase K, Kawano Y, Hayashi T, Iyama S, Takada K, Kuribayashi K, Sato Y, Kobune M, Takimoto R, Matsunaga T, Kato J, Niitsu Y

Journal of immunology (Baltimore, Md. : 1950) ( 1 )  181 ( 1 ) 197 - 207  2008年07月  [査読有り]

PubMed

Resolution of liver cirrhosis using vitamin A-coupled liposomes to deliver siRNA against a collagen-specific chaperone.

Sato Y, Murase K, Kato J, Kobune M, Sato T, Kawano Y, Takimoto R, Takada K, Miyanishi K, Matsunaga T, Takayama T, Niitsu Y

Nature biotechnology ( 4 )  26 ( 4 ) 431 - 442  2008年04月  [査読有り]

DOI PubMed

[An advanced metastatic breast cancer patient successfully treated with combination therapy including docetaxel, doxorubicin and cyclophosphamide (TAC) as salvage therapy].

Sato Y, Takayama T, Sagawa T, Sato T, Okamoto K, Takahashi S, Abe S, Iyama S, Murase K, Kato J, Niitsu Y

Gan to kagaku ryoho. Cancer & chemotherapy ( 3 )  35 ( 3 ) 471 - 473  2008年03月  [査読有り]

PubMed

Successful treatment of chronic myeloproliferative disease-unclassifiable (CMPD-U) with no chromosomal abnormalities by imatinib mesylate

Satoshi Iyama, Takuya Matsunaga, Tsutomu Sato, Kazuyuki Murase, Naoko Araki, Rishu Takimoto, Masayoshi Kobune, Tamotsu Sagawa, Tetsuji Takayama, Yoshiro Niitsu

INTERNAL MEDICINE ( JAPAN SOC INTERNAL MEDICINE )  47 ( 8 ) 791 - 794  2008年  [査読有り]

　概要を見る

We report a chronic myeloproliferative disease-unclassifiable (CMPD-U) patient who achieved hematological remission following imatinib mesylate (imatinib). Chromosomal and molecular analyses demonstrated no genetic abnormalities of c-abl, bcr-abl, c-kit or platelet-derived growth factor receptor (PDGFR) genes from hematopoietic cells. Although there has been one report of CMPD-U patient with chromosomal abnormalities of the PDGFR gene having complete hematologic responses upon treatment with imatinib, there have not been similar reports of patients without chromosomal abnormalities. This is the first case report of a CMPD-U patient with no chromosomal abnormalities who completely responded to treatment with imatinib.

DOI PubMed

Successful treatment of autoimmune pancreatitis complicated with autoimmune thrombocytopenia and interstitial pneumonia by prednisolone

Kazuyuki Murase, Takuya Matsunaga, Tsuyoshi Hayashi, Hirotoshi Ishiwatari, Naoko Araki, Satoshi Iyama, Tsutomu Sato, Masayoshi Kobune, Rishu Takimoto, Koji Miyanishi, Toru Miyazaki, Hisami Ikeda, Junji Kato, Yoshiro Niitsu

INTERNAL MEDICINE ( JAPAN SOC INTERNAL MEDICINE )  47 ( 11 ) 1033 - 1038  2008年  [査読有り]

　概要を見る

We report the second patient diagnosed with autoimmune pancreatitis complicated with autoimmune thrombocytopenia and interstitial pneumonia. The patient was treated with prednisolone and responded favorably. We demonstrated that anti-platelet (PLT) antibody of the patient was IgG4 and that it may react with HLA, not specific antigen, on both pancreas and PLT.

DOI PubMed