研究者詳細 - 井山　諭

論文 - 井山　諭

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[Enteropathy-type T-cell lymphoma with CD8 and CD56 expression].

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

[Rinsho ketsueki] The Japanese journal of clinical hematology ( 7 ) 47 645 - 649 2006年07月 [査読有り]

Human herpesvirus-6 hepatitis associated with cyclosporine-A encephalitis after bone marrow transplantation for chronic myeloid leukemia

Kageaki Kuribayashi, Takuya Matsunaga, Satoshi Iyama, Koichi Takada, Tsutomu Sato, Kazuyuki Murase, Akihito Fujimi, Rishu Takimoto, Johji Kawanishi, Yoshiro Niitsu

INTERNAL MEDICINE ( JAPAN SOC INTERNAL MEDICINE ) 45 ( 7 ) 475 - 478 2006年 [査読有り]

A 31-year-old man referred to our hospital for treatment of his chronic myeloid leukemia (CML) in the first chronic phase by bone marrow transplantation. We pretreated him with cyclophosphamide and total body irradiation and bone marrow transplantation (BMT) was carried out. On day 31, the engraftment was confirmed and on day 52, acute graft versus host disease (GVHD) was observed. On day 189, he lost consciousness due to cyclosporine A-induced leukoencephalopathy and 375 mg cyclosporine A was changed to 100 mg prednisolone. On day 199, liver dysfunction (AST 410 IU/L, ALT 557 IU/L, gamma GTP 385 IU/L, ALP 363 IU/L, D-Bil 0.3 mg/dl) developed and a liver biopsy was performed. PCR analysis of DNA from the liver biopsy specimen was positive for HHV-6 and immunostaining using anti-HHV-6 and anti-HHV-6b antibodies showed positive staining in the cytosol of hepatocytes. No other viruses were found to induce hepatitis. From these results, he was diagnosed as having HHV-6 hepatitis and it was successfully treated with gancyclovir (GCV) administration.

DOI PubMed

[Two cases of primary skeletal muscle lymphoma, and a review of the literature].

Ueno A, Kuribayashi K, Iyama S, Matsunaga T, Kikuchi S, Sato T, Kobune M, Takimoto R, Kato J, Niitsu Y

[Rinsho ketsueki] The Japanese journal of clinical hematology ( 10 ) 46 1141 - 1145 2005年10月 [査読有り]

DOI PubMed

[Essential thrombocythemia associated with incomplete type intestinal Behçet disease during hydroxyurea treatment].

Kobune M, Kato J, Kuribayashi K, Iyama S, Fujimi A, Murase K, Ueno A, Kikuchi S, Satoh T, Okamoto T, Takimoto R, Matsunaga T, Niitsu Y

[Rinsho ketsueki] The Japanese journal of clinical hematology 46 ( 10 ) 1136 - 1140 2005年10月 [査読有り]

DOI PubMed

Donor cell derived acute myeloid leukemia after allogeneic cord blood transplantation in a patient with adult T-cell lymphoma

T Matsunaga, K Murase, M Yoshida, A Fujimi, S Iyama, K Kuribayashi, T Sato, K Kogawa, Y Hirayama, S Sakamaki, K Kohda, Y Niitsu

AMERICAN JOURNAL OF HEMATOLOGY ( WILEY-LISS ) 79 ( 4 ) 294 - 298 2005年08月 [査読有り]

We report a patient with adult T-cell lymphoma who developed acute myeloid leukemia (AML) after allogeneic cord blood transplantation (CBT). Fluorescence in situ hybridization (FISH) studies and molecular analysis using short tandem repeat (STR) sequences proved the AML to be of donor origin. Although 25 cases of donor cell leukemia (DCL) occurring after allogeneic bone marrow transplantation have previously been reported, there have been no reports of DCL after CBT. This case is the first-reported DCL patient after CBT.

DOI PubMed

Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion

Y Sato, H Araki, J Kato, K Nakamura, Y Kawano, M Kobune, T Sato, K Miyanishi, T Takayama, M Takahashi, R Takimoto, S Iyama, T Matsunaga, S Ohtani, A Matsuura, H Hamada, Y Niitsu

BLOOD ( AMER SOC HEMATOLOGY ) 106 ( 2 ) 756 - 763 2005年07月 [査読有り]

Hepatic transdifferentiation of bone marrow cells has been previously demonstrated by intravenous administration of donor cells, which may recirculate to the liver after undergoing proliferation and differentiation in the recipient's bone marrow. In the present study, to elucidate which cellular components of human bone marrow more potently differentiate into hepatocytes, we fractionated human bone marrow cells into mesenchymal stem cells (MSCs), CD34(+) cells, and non-MSCs/ CD34(-) cells and examined them by directly xenografting to allylalcohol (AA)- treated rat liver. Hepatocyte-like cells, as revealed by positive immunostaining for human-specific alpha-fetoprotein (AFP), albumin (Alb), cytokeratin 19 (CK19), cytokeratin 18 (CK18), and asialoglycoprotein receptor (AGPR), and by reverse transcription-polymerase chain reaction (RTPCR) for expression of AFP and Alb mRNA, were observed only in recipient livers with MSC fractions. Cell fusion was not likely involved since both human and rat chromosomes were independently identified by fluorescence in situ hybridization (FISH). The differentiation appeared to follow the process of hepatic ontogeny, reprogramming of gene expression in the genome of MSCs, as evidenced by expression of the AFP gene at an early stage and the albumin gene at a later stage. In conclusion, we have demonstrated that MSCs are the most potent component in hepatic differentiation, as revealed by directly xenografting into rat livers.

DOI PubMed

[Successful treatment with oral ribavirin of adenovirus-associated hemophagocytic syndrome in a stem cell transplantation recipient].

Iyama S, Matsunaga T, Fujimi A, Murase K, Kuribayasi K, Sato T, Hirayama Y, Sakamaki S, Kohda K, Niitsu Y

[Rinsho ketsueki] The Japanese journal of clinical hematology ( 5 ) 46 ( 5 ) 363 - 367 2005年05月 [査読有り]

症例は51歳，女性。重症型再生不良性貧血の診断にて，2003年1月28日にHLA一致同胞より同種末梢血幹細胞移植を施行した。Day 207にアデノウイルスによる出血性膀胱炎を発症し，adenine arabinosideの投与を開始したが改善がみられず，腎炎へと移行した。Day 228にアデノウイルス関連血球貪食症候群を併発した。経口ribavirin投与後に出血性膀胱炎，腎機能障害のみならず，血球貪食症候群による汎血球減少も改善した。これまで造血幹細胞移植後に発症するアデノウイルス感染症に対しては治療法が確立されていない。示唆に富む症例と考え報告する。

DOI PubMed CiNii

Prolonged survival of mice with multiple liver metastases of human colon cancer by intravenous administration of replicable E1B-55K-deleted adenovirus with E1A expressed by CEA promoter

T Sagawa, M Takahashi, T Sato, Y Sato, Y Lu, T Sumiyoshi, Y Yamada, S Iyama, J Fukaura, K Sasaki, H Hamada, K Miyanishi, T Takayama, J Kato, Y Niitsu

MOLECULAR THERAPY ( ACADEMIC PRESS INC ELSEVIER SCIENCE ) 10 ( 6 ) 1043 - 1050 2004年12月 [査読有り]

Liver is the most preferential site for metastasis of colon cancer. We, in the present study, constructed a self-replicable adenovirus in which EIIA is driven by a CEA promoter and E1B-55K is deleted from the E1B region (AdCEAp/Rep) and examined its effects on multiple metastases of a human colon cancer cell in a mouse xenograft model. We first showed effective replication of the virus in various CEA-producing human colon cancer cells (M7609, HT-29) and subsequent lysis of the infected cells in vitro. We then demonstrated that a single intratumoral injection of the virus (1 x 10(8) PFU/100 mul) induced a complete regression of subcutaneous tumors (M7609) inoculated into nude mice. Further, we demonstrated that systemic administration of the virus (1 x 10(8) PFU/100 mul) through the tail vein to nude mice, which 1 week prior had been inoculated with tumor cells (colon carcinoma cell line HT-29) via the spleen and showed apparent multiple metastases in the liver, effectively suppressed the metastasis formation. The mean survival time of the treated mice was significantly longer than that of the controls. Thus, the systemic administration of AdCEAp/Rep was considered to be effective on multiple liver metastases of CEA-positive colon cancer in a xenograft model.

DOI PubMed

Interleukin-11 as an osteoprotegerin-inducing factor in culture medium of blastic cells from a patient with acute megakaryocytic leukemia complicated with osteosclerosis

T Sato, T Matsunaga, M Kida, K Morii, T Machida, Y Kawano, K Nakamura, K Kuribayashi, K Takada, S Iyama, Y Sato, T Takayama, M Takahashi, J Kato, M Chokki, Y Niitsu

AMERICAN JOURNAL OF HEMATOLOGY ( WILEY-LISS ) 77 ( 1 ) 62 - 66 2004年09月 [査読有り]

We came across a rare case of acute megalkaryocytic leukemia, the clinical course of which was relatively chronic and nonaggressive. This case was complicated with generalized severe osteosclerosis (OS). The medium in which blastic cells from the patient were cultured showed a strong activity to enhance the expression of an osteosclerotic cytokine, osteoprotegerin (OPG), as revealed by real-time quantitative RT-PCR and Western blot analysis. The OPG-inducing activity of the culture medium was neutralized by the anti-interieukin-11 (IL-11) antibody. These results indicate that IL-11 produced by the blasts was a causative factor of the OS observed in this patient. (C) 2004 Wiley-Liss, Inc.

DOI PubMed

遺伝子治療 AFP産生肝癌に対する制限増殖型アデノウイルス,p53遺伝子,5-FUの3者併用は高い抗腫瘍効果を示す

山田康之, 高橋稔, 佐川保, 佐藤康史, 佐藤勉, 深浦純生, 井山諭, 佐々木勝則, 中村公則, 濱田洋文, 新津洋司郎

日本癌治療学会誌 ( (一社)日本癌治療学会 ) 39 ( 2 ) 397 - 397 2004年09月

Fas-mediated apoptosome formation is dependent on reactive oxygen species derived from mitochondrial permeability transition in Jurkat cells

T Sato, T Machida, S Takahashi, S Iyama, Y Sato, K Kuribayashi, K Takada, T Oku, Y Kawano, T Okamoto, R Takimoto, T Matsunaga, T Takayama, M Takahashi, J Kato, Y Niitsu

JOURNAL OF IMMUNOLOGY ( AMER ASSOC IMMUNOLOGISTS ) 173 ( 1 ) 285 - 296 2004年07月 [査読有り]

Generation of reactive oxygen species (ROS) and activation of caspase cascade are both indispensable in Fas-mediated apoptotic signaling. Although ROS was presumed to affect the activity of the caspase cascade on the basis of findings that antioxidants inhibited the activation of caspases and that the stimulation of ROS by itself activated caspases, the mechanism by which these cellular events are integrated in Fas signaling is presently unclear. In this study, using human T cell leukemia Jurkat cells as well as an in vitro reconstitution system, we demonstrate that ROS are required for the formation of apoptosome. We first showed that ROS derived from mitochondrial permeability transition positively regulated the apoptotic events downstream of mitochondrial permeability transition. Then, we revealed that apoptosome formation in Fas-stimulated Jurkat cells was clearly inhibited by N-acetyl-L-cysteine and manganese superoxide dismutase by using both the immunoprecipitation and size-exclusion chromatography methods. To confirm these in vivo findings, we next used an in vitro reconstitution system in which in vitro-translated apoptotic protease-activating factor 1 (Apaf-1), procaspase-9, and cytochrome c purified from human placenta were activated by dATP to form apoptosome; the formation of apoptosome was markedly inhibited by reducing reagents such as DTT or reduced glutathione (GSH), whereas hydrogen peroxide prevented this inhibition. We also found that apoptosome formation was substantially impaired by GSH-pretreated Apaf-1, but not GSH-pretreated procaspase-9 or GSH-pretreated cytochrome c. Collectively, these results suggest that ROS plays an essential role in apoptosome formation by oxidizing Apaf-1 and the subsequent activation of caspase-9 and -3.

PubMed

[A case of gastric carcinoma with multiple skin, bone, and bilateral ovary metastasis; effective treatment by chemotherapy].

Mezawa S, Homma H, Doi T, Akiyama T, Murakami K, Kogawa K, Hirata K, Kida M, Murase K, Iyama S

Gan to kagaku ryoho. Cancer & chemotherapy ( 12 ) 30 1973 - 1975 2003年11月 [査読有り]

PubMed

Superselective transcatheter embolization for acute lower gastrointestinal hemorrhage after endoscopic mucosal resection: A report of 3 cases

S Mezawa, H Homma, K Murase, T Doi, S Iyama, K Takada, K Hirata, F Mezawa, Y Niitsu

HEPATO-GASTROENTEROLOGY ( H G E UPDATE MEDICAL PUBLISHING S A ) 50 ( 51 ) 735 - 737 2003年05月 [査読有り]

One of the most common complications related to endoscopic mucosal resection is hemorrhage; in almost every case, the bleeding is endoscopically managed, but some cases are unresponsive to the treatment. We have encountered three cases of endoscopically uncontrollable lower gastrointestinal hemorrhage after endoscopic mucosal resection in the colon which we successfully treated by urgent superselective transcatheter embolization. In our three cases, massive hemorrhage occurred immediately after endoscopic mucosal resection of a sessile polyp 25-40mm in diameter, two cases in the ascending colon and one in the rectum. Although hemoclip placement was attempted in every case, hemostasis was not achieved. Emergency angiography disclosed massive extravasation of the contrast material in the colon. Hemostasis was achieved immediately after superselective transcatheter arterial embolizations with microcoils, with no observable ischemic complications and without the need of transfusions. In conclusion, superselective transcatheter embolization with microcoils should be considered a safe and efficient treatment option for endoscopically uncontrollable lower gastrointestinal hemorrhage occurring after endoscopic mucosal resection.

PubMed

[A case responding to weekly paclitaxel (TXL) therapy as third line chemotherapy for scirrhous type gastric cancer].

Sagawa T, Tsuji Y, Takayanagi N, Hirayama Y, Sakamaki S, Chiba H, Nakajima T, Iyama S, Oku T, Sumiyoshi T, Sato Y, Takahashi M, Takayama T, Niitsu Y

Gan to kagaku ryoho. Cancer & chemotherapy ( 5 ) 30 707 - 710 2003年05月 [査読有り]

PubMed

[A case of irinotecan-resistant colon cancer responding to chronotherapy with oxaliplatin, 5-FU, l-LV].

Sagawa T, Tsuji Y, Takayanagi N, Hirayama Y, Sakamaki S, Chiba H, Iyama S, Oku T, Sato Y, Takahashi M, Takayama T, Niitsu Y

Gan to kagaku ryoho. Cancer & chemotherapy ( 4 ) 30 537 - 543 2003年04月 [査読有り]

PubMed

肝腫瘍に対する食塩水注入併用ラジオ波凝固療法による播種の危険性

太田英敏, 新谷直昭, 高橋康雄, 藤川幸司, 井山諭, 中村とき子

肝臓 ( 一般社団法人日本肝臓学会 ) 43 ( 12 ) 583 - 583 2002年12月

DOI CiNii

[Usefulness of CT arteriography for transcatheter peripancreatic arterial embolization to patients with advanced pancreatic cancer].

Doi T, Homma H, Mezawa S, Akiyama T, Machida T, Murakami K, Hirata K, Takanashi N, Iyama S, Niitsu Y

Gan to kagaku ryoho. Cancer & chemotherapy ( 12 ) 29 2298 - 2301 2002年11月 [査読有り]

PubMed

Induction of heat shock protein 47 synthesis by TGF-beta and IL-1 beta via enhancement of the heat shock element binding activity of heat shock transcription factor 1

H Sasaki, T Sato, N Yamauchi, T Okamoto, D Kobayashi, S Iyama, J Kato, T Matsunaga, R Takimoto, T Takayama, K Kogawa, N Watanabe, Y Niitsu

JOURNAL OF IMMUNOLOGY ( AMER ASSOC IMMUNOLOGISTS ) 168 ( 10 ) 5178 - 5183 2002年05月 [査読有り]

With most immunological reactions, tissue fibrosis, collagen overproduction caused by immune cytokines, is inevitably associated. Among the various immune cytokines, heat shock protein 47 (HSP47) is a procollagen-specific molecular chaperon and is essential for secretion of procollagen from cells. Induction of HSP47 by TGF-beta has been previously reported in rat skeletal myoblasts and mouse osteoblasts, but not in human diploid fibroblasts. As for IL-1beta, its effect on HSP47 has not been elucidated. In the present study, using human embryonic lung fibroblast cells, we first disclosed that both TGF-beta and IL-1beta induced HSP47 synthesis. We then revealed that the binding of the heat shock element (HSE) by heat shock transcription factor 1 (HSF1) was enhanced by both cytokines. We further demonstrated that trimer formation of HSF1, which is essential for its binding to HSE, was induced by these cytokines. The enhancement of HSP47 synthesis and their trimer formation of HSF1 were augmented by using a combination of both cytokines. Collectively, TGF-beta and IL-1beta were found to induce trimer formation of HSF1 which in turn bound to HSE of HSP47, resulting in the enhancement of HSP47 expression. Thus, HSP47 could well be a good candidate for molecular targeting in controlling tissue fibrosis, given that both principal fibrinogenetic cytokines (TGF-beta, IL-1beta) are commonly involved in its induction through HSF1 trimerization.

PubMed

E1B-55K-deleted adenovirus expressing E1A-13S by AFP-enhancer/promoter is capable of highly specific replication in AFP-producing hepatocellular carcinoma and eradication of established tumor

M Takahashi, T Sato, T Sagawa, Y Lu, Y Sato, S Iyama, Y Yamada, J Fukaura, S Takahashi, K Miyanishi, T Yamashita, K Sasaki, K Kogawa, H Hamada, J Kato, Y Niitsu

MOLECULAR THERAPY ( ACADEMIC PRESS INC ELSEVIER SCIENCE ) 5 ( 5 ) 627 - 634 2002年05月 [査読有り]

Here, we constructed a recombinant replication-competent adenovirus (rRCAd; AdAFPep/Rep) that expresses both E1A-13S driven by the alpha-fetoprotein (AFP) enhancer/promoter (AFPep) lacking any silencers in the 5'-flanking region of the AFP gene, and 55K-deleted E1B driven by the cytomegalovirus (CMV) promoter. We then examined the feasibility of gene therapy utilizing this virus for AFP-producing hepatocellular carcinoma (HCC). AdAFPep/Rep lysed all the AFP-producing HCC cell lines (HuH7, HepG2, PLC/PRF/5 (P5)) examined at a multiplicity of infection (MOI) as low as 0.1 and did not lyse primary human hepatocytes (Hc) at a MOI as high as 100, indicating that the rRCAd virus can lyse AFP-producing HCC cells with a higher specificity and potency than previously reported. Furthermore, this virus was capable of complete eradication of a preestablished HuH7-cell tumor by a single intratumoral injection of 10(8) plaque-forming units (pfu) of AdAFPep/Rep. Thus, AdAFPep/Rep may be applicable for clinical use.

DOI PubMed

Treatment of murine collagen-induced arthritis by ex vivo extracellular superoxide dismutase gene transfer.

Iyama S, Okamoto T, Sato T, Yamauchi N, Sato Y, Sasaki K, Takahashi M, Tanaka M, Adachi T, Kogawa K, Kato J, Sakamaki S, Niitsu Y

Arthritis and rheumatism 44 ( 9 ) 2160 - 2167 2001年09月 [査読有り]

PubMed CiNii

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