Susumu Ikehara

Kansai Medical University, Moriguchi, Ōsaka, Japan

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Publications (439)1832.2 Total impact

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    ABSTRACT: Angioimmunoblastic T cell lymphoma (AITL) is a peripheral T cell lymphoma, known to express CD3 and CD4, and, frequently, also CD10 and c‑Maf‑1. Hypergammaglobulinemia is not particularly rare in patients with AITL. However, AITL in conjunction with plasmacytosis in the peripheral blood is rare. The current report presents a case of CD10‑negative AITL demonstrating leukemic change and plasmacytosis in the peripheral blood mimicking plasma cell leukemia. A 78‑year‑old male was admitted to hospital due to systemic lymph node enlargement, high serum IgG and IgA, and increased counts of plasmacytoid cells and lymphoid cells with atypical nuclei in the peripheral blood. Initially, plasma cell leukemia was suspected, due to the extreme increase in the number of plasma cells in the peripheral blood. However, the plasma cells did not show clonal expansion on examination by flow cytometry. Based on histological analyses, following a biopsy of an enlarged lymph node, the patient was diagnosed with AITL. This case suggests that when hypergammaglobulinemia and increases in B‑lineage cells are observed, AITL should be considered in addition to disorders of B-lineage cells.
    Oncology letters 07/2015; 10(3). DOI:10.3892/ol.2015.3490 · 1.55 Impact Factor
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    ABSTRACT: Most thymic carcinomas aberrantly express the lymphocyte marker CD5. This study was performed to examine the role of the self-reactive CD5 antigen in thymic carcinoma. We examined CD5 expression in thymic carcinoma in relation to the lymphoid stroma. All cases of thymic carcinoma examined expressed CD5. A number of CD5(+) lymphocytes were also present in the stroma of thymic carcinoma. The CD5(+) tumour areas were predominantly in contact with the lymphoid stroma, and the expression level was significantly lower in tumour cells than lymphocytes. Although p53 and Bcl-2 expression levels were significantly higher in thymic carcinoma than normal thymic epithelial cells (TECs), they did not differ between CD5(+) and CD5(-) areas. E-cadherin expression in thymic carcinoma was comparable with that of normal TECs, and it also did not differ between these areas. In contrast, both Ki-67 index and mitotic activity were significantly higher in thymic carcinoma than normal TECs, and they were significantly higher in CD5(+) than CD5(-) areas. CD5 may be induced by interaction with CD5(+) lymphoid stoma, and may be related to tumour proliferation. CD5 induction may also be a significant and/or specific effect of the tumour microenvironment of the thymus. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Histopathology 05/2015; DOI:10.1111/his.12742 · 3.45 Impact Factor
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    ABSTRACT: GVHD is a crucial mortality factor in allogeneic bone marrow transplantation (ABMT). In this paper, we show that dehydroxymethylepoxyquinomicin (DHMEQ), a novel inhibitor of nuclear factor-κB, suppresses GVHD, resulting in an improved mortality rate in a mouse ABMT model. Bone marrow cells from C57BL/6 mice (B6 mice) were transplanted into lethally irradiated BALB/c mice. Two weeks later, spleen cells from B6 mice were transplanted into the irradiated BALB/c mice. From one week after the injection of spleen cells, when the mice started to show GVHD, the mice were also injected intraperitoneally daily with DHMEQ or vehicle only (DMSO) for 4 weeks. By 80 days after the ABMT, 6/14 of the vehicle-injected mice (43%) had died because of GVHD, whereas all DHMEQ-injected mice survived this observation period and developed milder GVHD than the vehicle-injected mice. When regulatory T cells were reduced by the injection of anti-folate receptor 4 (FR4) antibody, the effects of DHMEQ were reduced. These findings suggest that administration of DHMEQ could become a new strategy for preventing fatalities from GVHD. Copyright © 2015 Elsevier GmbH. All rights reserved.
    Immunobiology 05/2015; 220(9). DOI:10.1016/j.imbio.2015.05.011 · 3.04 Impact Factor
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    ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is associated with insulin resistance, oxidative stress, and obesity. The db/db mouse model displays increased levels of insulin resistance, obesity, and an over-accumulation of hepatic triglycerides, making it an excellent model for studying NAFLD. In db/db mice, intra-bone marrow-bone marrow transplantation plus thymus transplantation (IBM-BMT+TT) improves type 2 diabetes mellitus (T2 DM) by normalizing the T-cell imbalance. We hypothesized that this approach would improve Sirt1 expression in the liver and benefit liver development. The db/db mice were treated with IBM-BMT+TT, and plasma MCP-1, IL-6, adiponection, LDL, Sirt1, and HO-1 levels were then assessed. Stem cell transplantation decreased the levels of plasma inflammatory cytokines and LDL while it increased the expression of Sirt1 and HO-1, resulting in decreased progression of fatty liver. Moreover, Sirt1 and HO-1 expression were both detected in the thymus and many HO-1-positive cells were observed in the bone marrow. This is the first report of stem cell transplantation improving the antioxidant function in the liver, thymus, and bone marrow of db/db mice by increasing the levels of Sirt1 and HO-1. This approach may prove useful in the treatment of nonalcoholic steatohepatitis and its clinical manifestations.
    International journal of biological sciences 03/2015; 11(4):472-81. DOI:10.7150/ijbs.10809 · 4.51 Impact Factor
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    ABSTRACT: Bone marrow-derived cells enter the brain in a non-inflammatory condition through the attachments of choroid plexus and differentiate into ramified myeloid cells. Neurodegenerative conditions may be associated with altered immune-brain interaction. The senescence-accelerated mouse prone 10 (SAMP10) undergoes earlier onset neurodegeneration than C57BL/6 (B6) strain. We hypothesized that the dynamics of immune cells migrating from the bone marrow to the brain is perturbed in SAMP10 mice. We created 4 groups of radiation chimeras by intra-bone marrow-bone marrow transplantation using 2-month-old (2 mo) and 10 mo SAMP10 and B6 mice as recipients with GFP transgenic B6 mice as donors, and analyzed histologically 4 months later. In the [B6 → 10 mo SAMP10] chimeras, more ramified marrow-derived cells populated a larger number of discrete brain regions than the other chimeras, especially in the diencephalon. Multiplex cytokine assays of the diencephalon prepared from non-treated 3 mo and 12 mo SAMP10 and B6 mice revealed that 12 mo SAMP10 mice exhibited higher tissue concentrations of CXCL1, CCL11, G-CSF, CXCL10 and IL-6 than the other groups. Immunohistologically, choroid plexus epithelium and ependyma produced CXCL1, while astrocytic processes in the attachments of choroid plexus expressed CCL11 and G-CSF. The median eminence produced CXCL10, hypothalamic neurons G-CSF and tanycytes CCL11 and G-CSF. These brain cytokine profile changes in 12 mo SAMP10 mice were likely to contribute to acceleration of the dynamics of marrow-derived cells to the diencephalon. Further studies on the functions of ramified marrow-derived myeloid cells would enhance our understanding of the brain-bone marrow interaction.
    Brain Structure and Function 01/2015; DOI:10.1007/s00429-014-0987-2 · 5.62 Impact Factor
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    Susumu Ikehara ·

    Immunome Research 01/2015; 11(2). DOI:10.4172/1745-7580.1000091
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    ABSTRACT: SKG/Jcl (SKG) mice spontaneously develop T cell-mediated autoimmune arthritis and may be an effective model for studying human rheumatoid arthritis. We sought to confirm that arthritis in SKG mice was caused by stem cell disorders. We induced systemic arthritis in normal C57/BL6 (B6) mice (H-2(b) type) by injecting lineage-negative (lin(-)) immature cells isolated from bone marrow cells (BMCs) of SKG mice (H-2(d) type) directly into bone cavities. Twenty weeks later, we analyzed arthritis scores, hematoxylin-eosin (H-E) staining and tartrate-resistant acid phosphatase (TRAP) staining in ankle joints, H-2 type of hematolymphoid and osteoblast-like cells, serum levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and percentages of CD4(+) T cells and osteoblast-like cells expressing receptor activator of nuclear factor kappa-B ligand (RANKL) in recipient mice. Donor-derived hematolymphoid cells and osteoblast-like cells had completely replaced donor-derived cells in the recipients (H-2(b) to H-2(d)). All recipients showed severe joint swelling with hyperemia and developed hypertrophic synovitis with lymphocytes accumulated around joints. All recipients also had higher TNF-α and IL-6 levels than untreated B6 controls. Furthermore, the percentages of CD4(+) T cells and osteoblast-like cells expressing RANKL and the number of TRAP(+) cells were greater in treated animals. Donor-derived hematolymphoid cells and osteoblast-like cells persisted in these recipients and promoted autoimmune arthritis and an increase in osteoclasts. Because autoimmune arthritis may be associated with abnormal lin(-) immature cells, patients with intractable autoimmune arthritis may be treated by replacing these cells with direct injection of lin(-) immature cells isolated from normal BMCs.
    Biological & Pharmaceutical Bulletin 11/2014; 37(11):1719-26. DOI:10.1248/bpb.b14-00302 · 1.83 Impact Factor
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    Ming Li · Kequan Guo · Susumu Ikehara ·
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    ABSTRACT: Alzheimer's disease (AD) is a progressive and neurodegenerative disorder that induces dementia in older people. It was first reported in 1907 by Alois Alzheimer, who characterized the disease as causing memory loss and cognitive impairment. Pathologic characteristics of AD are β-amyloid plaques, neurofibrillary tangles and neurodegeneration. Current therapies only target the relief of symptoms using various drugs, and do not cure the disease. Recently, stem cell therapy has been shown to be a potential approach to various diseases, including neurodegenerative disorders, and in this review, we focus on stem cell therapies for AD.
    International Journal of Molecular Sciences 10/2014; 15(10):19226-19238. DOI:10.3390/ijms151019226 · 2.86 Impact Factor
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    Ming Li · Kuquan Guo · Susumu Ikehara ·
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    ABSTRACT: Bone marrow transplantation (BMT) is used to treat hematological disorders, autoimmune diseases (ADs) and lymphoid cancers. Intra bone marrow-BMT (IBM-BMT) has been proven to be a powerful strategy for allogeneic BMT due to the rapid hematopoietic recovery and the complete restoration of T cell functions. IBM-BMT not only replaces hematopoietic stem cells (HSCs) but also mesenchymal stromal cells (MSCs). MSCs are multi-potent stem cells that can be isolated from bone marrow (BM), umbilical cord blood (UCB), and adipose tissue. MSCs play an important role in the support of hematopoiesis, and modify and influence the innate and adaptive immune systems. MSCs also differentiate into mesodermal, endodermal and ectodermal lineage cells to repair tissues. This review aims to summarize the functions of BM-derived-MSCs, and the treatment of intractable diseases such as rheumatoid arthritis (RA) and malignant tumors with IBM-BMT.
    Frontiers in Cell and Developmental Biology 09/2014; 2:48. DOI:10.3389/fcell.2014.00048
  • S. Hasegawa-Ishii · S. Ikehara · M. Inaba · M. Li · M. Shi · S. Takei · A. Shimada ·

    Brain Behavior and Immunity 09/2014; 40:e17. DOI:10.1016/j.bbi.2014.06.077 · 5.89 Impact Factor
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    ABSTRACT: Other than that in the duodenum, adenocarcinoma in the small bowel is rare. The present study describes a case of adenocarcinoma with adenoma in the jejunum. A 70-year-old male was admitted to hospital due to dehydration induced by abdominal discomfort and difficulty with oral intake. Computed tomography revealed a tumor in the upper side of the jejunum, which was subsequently resected. The tumor contained adenocarcinoma and adenoma. The protein expression of p53 and Ki-67 was analyzed in the normal mucosa, adenoma and adenocarcinoma. The number of epithelial cells expressing p53 and Ki-67 was found to increase in the adenoma tissue compared with that in the normal mucosa. In the adenocarcinoma tissue, the number of cells expressing p53 and Ki-67 further increased, suggesting that an adenoma-adenocarcinoma sequence may occur in the small bowel, similar to that observed in the large bowel.
    Oncology letters 08/2014; 8(2):633-636. DOI:10.3892/ol.2014.2210 · 1.55 Impact Factor
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    ABSTRACT: Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of B-cell lymphoma characterized by selective growth of clonal B-cells in the lumen of the small vessels of various organs including the liver, spleen, lungs, skin, brain, and kidney. An 86-year-old male presented with weight loss, fever and night sweats (known as B symptoms). Blood examination revealed pancytopenia, high lactate dehydrogenase and high soluble interleukin-2 receptor, suggesting hematopoietic malignancy. However, there were no abnormal hematopoietic cells in the peripheral blood. No lymph node swelling was identified on examination by whole-body computed tomography scan. Therefore, IVLBCL was suspected, and random skin biopsies and a skin biopsy from a senile hemangioma were carried out. A small number of large atypical lymphoid cells resided in the small blood vessels in the deep dermis and subcutaneous tissue of the random skin biopsies, and numerous atypical lymphoid cells were identified in the small vessels of the senile hemangioma. These results suggest the usefulness of skin biopsy from senile hemangiomas in the diagnosis of IVLBCL.
    Oncology letters 06/2014; 7(6):2003-2006. DOI:10.3892/ol.2014.2017 · 1.55 Impact Factor
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    Ming Shi · Ming Li · Yunze Cui · Yasushi Adachi · Susumu Ikehara ·
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    ABSTRACT: It has been shown that allogeneic intra-bone marrow-bone marrow transplantation (IBM-BMT) plus thymus transplantation (TT) is effective in treating recipients with malignant tumors. Although TT increases the percentage of T cells in the early term after BMT, the myeloid-derived suppressor cells (MDSCs) are still the dominant population. We used the Gr-1 Ab to deplete the granulocytic MDSCs (G-MDSCs) in tumor-bearing mice that had received BMT+TT. Two weeks after the BMT, the mice injected with Gr-1 Ab showed smaller tumors than those in the control group. In addition, Gr-1 Ab significantly increased the percentages and numbers of CD4+ and CD8+ T cells, and decreased the percentages and numbers of MDSCs and G-MDSCs. No side effects of the Gr-1 Ab on recipient or donor thymus were observed. These findings indicate that Gr-1 Ab administered after BMT+TT may enhance the effectiveness of tumor suppression.
    PLoS ONE 05/2014; 9(5):e97908. DOI:10.1371/journal.pone.0097908 · 3.23 Impact Factor
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    Susumu Ikehara · Ming Li ·
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    ABSTRACT: Aging is a complex process of damage accumulation, and has been viewed as experimentally and medically intractable. The number of patients with age-associated diseases such as type 2 diabetes mellitus (T2DM), osteoporosis, Alzheimer's disease (AD), Parkinson's disease, atherosclerosis, and cancer has increased recently. Aging-related diseases are related to a deficiency of the immune system, which results from an aged thymus and bone marrow cells. Intra bone marrow-bone marrow transplantation (IBM-BMT) is a useful method to treat intractable diseases. This review summarizes findings that IBM-BMT can improve and treat aging-related diseases, including T2DM, osteoporosis and AD, in animal models.
    Frontiers in Cell and Developmental Biology 05/2014; 2:16. DOI:10.3389/fcell.2014.00016
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    ABSTRACT: Pulmonary sclerosing hemangioma (SH) is an uncommon benign or low-grade malignant tumor. Multicentric SH and SH with lymph node metastasis have rarely been reported. The present report describes a case of pulmonary SH with lymph node metastasis in a middle-aged female. A nodule was found incidentally in the lower left lung. The patient underwent left lower pulmonary lobectomy and lymph node dissection. Histologically, the nodule demonstrated the characteristic features of SH and one of the resected lymph nodes contained a metastasis of this tumor. Thus, pulmonary SH has the potential to metastasize, a potential not suggested by histological features.
    Oncology letters 04/2014; 7(4):997-1000. DOI:10.3892/ol.2014.1831 · 1.55 Impact Factor
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    Ming Li · Susumu Ikehara ·
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    ABSTRACT: Type 1 diabetes mellitus (T1DM) is a common chronic disease in children, characterized by a loss of β cells, which results in defects in insulin secretion and hyperglycemia. Chronic hyperglycemia causes diabetic complications, including diabetic nephropathy, neuropathy, and retinopathy. Curative therapies mainly include diet and insulin administration. Although hyperglycemia can be improved by insulin administration, exogenous insulin injection cannot successfully mimic the insulin secretion from normal β cells, which keeps blood glucose levels within the normal range all the time. Islet and pancreas transplantation achieves better glucose control, but there is a lack of organ donors. Cell based therapies have also been attempted to treat T1DM. Stem cells such as embryonic stem cells, induced pluripotent stem cells and tissue stem cells (TSCs) such as bone marrow-, adipose tissue-, and cord blood-derived stem cells, have been shown to generate insulin-producing cells. In this review, we summarize the most-recently available information about T1DM and the use of TSCs to treat T1DM.
    Frontiers in Cell and Developmental Biology 03/2014; 2:9. DOI:10.3389/fcell.2014.00009
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    Kequan Guo · Susumu Ikehara · Xu Meng ·
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    ABSTRACT: Organ transplantation is useful for treating the end stage of organ failure. The induction of tolerance to the transplanted organ is essential for its long-term survival. Immunologic tolerance can be induced by immunosuppressive agents and mixed chimerism. Mixed chimerism is a state in which both recipient-and donor-derived blood cells remain in the hematopoietic system after allogeneic hematopoietic stem cells have been transplanted. Mesenchymal stem cells (MSCs), and immune cells such as dendritic cells and T-reg cells play an important role in the induction of tolerance. MSCs secrete cytokines, which modulate the immune response. In particular, they upregulate T-reg cell function and thereby induce tolerance. Intra-bone marrow-bone marrow transplantation recruits both donor-derived HSCs and MSCs, inducing persistent donor-specific tolerance without the use of immunosuppressants. In this review, we summarize the use of MSCs to induce tolerance in organ transplantation.
    Frontiers in Cell and Developmental Biology 03/2014; 2:8. DOI:10.3389/fcell.2014.00008
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    Susumu Ikehara ·

    Frontiers in Cell and Developmental Biology 10/2013; 1:2. DOI:10.3389/fcell.2013.00002
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    ABSTRACT: For immunodeficient patients, fungi are life-threatening pathogens. In this paper, we present an autopsy case of combined zygomycosis and aspergillosis. A female in her 70s on chronic hemodialysis was admitted to a hospital suffering bloody sputum, dyspnea, and fever, probably due to perinuclear anti-neutrophil cytoplasmic antibody-related vasculitis. Antibiotics were administered and immunosuppressive therapy was started, resulting in an improvement in her condition. Pneumonia later developed, followed by pulmonary bleeding and intractable pneumothorax from which she ultimately died. On autopsy, the upper lobe of the left lung was found to have hemorrhagic necrosis and showed a large longitudinal fissure. Microscopically, Zygomycota were observed in both the lungs and heart, while Aspergillus was found in the middle lobe of the right lung. Zygomycosis, which usually has a poor prognosis, is assumed to have induced hemorrhagic infarction of the lungs, inducing pulmonary bleeding and necrosis, despite the use of lipid formulations of amphotericin B, which are effective medicines against Zygomycota.
    International Journal of General Medicine 07/2013; 6:575-9. DOI:10.2147/IJGM.S44701
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    Ming Li · Susumu Ikehara ·
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    ABSTRACT: Diabetes mellitus (DM) is a group of metabolic diseases in which a person has high blood glucose levels resulting from defects in insulin secretion and insulin action. The chronic hyperglycemia damages the eyes, kidneys, nerves, heart, and blood vessels. Curative therapies mainly include diet, insulin, and oral hypoglycemic agents. However, these therapies fail to maintain blood glucose levels in the normal range all the time. Although pancreas or islet-cell transplantation achieves better glucose control, a major obstacle is the shortage of donor organs. Recently, research has focused on stem cells which can be classified into embryonic stem cells (ESCs) and tissue stem cells (TSCs) to generate functional β cells. TSCs include the bone-marrow-, liver-, and pancreas-derived stem cells. In this review, we focus on treatment using bone marrow stem cells for type 1 and 2 DM.
    Journal of Diabetes Research 04/2013; 2013:329596. DOI:10.1155/2013/329596 · 2.16 Impact Factor

Publication Stats

13k Citations
1,832.20 Total Impact Points


  • 1987-2015
    • Kansai Medical University
      • • Department of Paediatrics
      • • Department of Ophthalmology
      • • Department of Orthopaedic Surgery
      • • Department of Otolaryngology
      • • Second Department of Internal Medicine
      Moriguchi, Ōsaka, Japan
    • Osaka Medical College
      • Department of Pathology
      Takatuki, Ōsaka, Japan
  • 2010
    • Fred Hutchinson Cancer Research Center
      • Division of Clinical Research
      Seattle, Washington, United States
  • 1984-2009
    • Kyoto University
      • • Department of Zoology
      • • Department of Dermatology
      Kioto, Kyōto, Japan
  • 2008
    • Jilin University
      Yung-chi, Jilin Sheng, China
  • 1997-1998
    • All Children's Hospital
      فلوريدا سيتي، فلوريدا, Florida, United States
  • 1994
    • Cornell University
      • Department of Pediatrics
      Итак, New York, United States
    • University of Ulsan
      • College of Medicine
      Urusan, Ulsan, South Korea
  • 1989-1994
    • University of South Florida St. Petersburg
      St. Petersburg, Florida, United States
  • 1989-1993
    • Osaka Red Cross Hospital
      Ōsaka, Ōsaka, Japan
  • 1992
    • Osaka City University
      • Second Department of Internal Medicine
      Ōsaka, Ōsaka, Japan
  • 1991
    • Osaka University
      • Division of Cellular and Molecular Biology
      Suika, Ōsaka, Japan
    • Hokkaido University
      • Institute of Immunological Science
      Sapporo, Hokkaidō, Japan
  • 1990
    • Kyoto Prefectural University of Medicine
      Kioto, Kyōto, Japan