The Keio Journal of Medicine
Online ISSN : 1880-1293
Print ISSN : 0022-9717
ISSN-L : 0022-9717
Volume 54 , Issue 3
Showing 1-5 articles out of 5 articles from the selected issue
REVIEWS
  • Junichiro Irie, William M. Ridgway
    2005 Volume 54 Issue 3 Pages 121-126
    Published: 2005
    Released: June 20, 2006
    JOURNALS FREE ACCESS
    The traditional overarching concept of disease pathogenesis entails the natural history of disease, i.e. the concept that any disease is a unified entity from beginning to termination. The concept of the natural history of disease encourages researchers and clinicians alike to conceptualize all clinical signs and symptoms in a patient as manifestations of a single disease process. Our experiences in dissecting the genetic control of autoimmune diseases and autoimmune phenotypes sugges that for many autoimmune processes, an alternative conceptual framework may be more useful. We term this approach a “modular” theory of autoimmunity. “Modules” are distinct, genetically controlled clinical or pathological phenotypes which can interact to construct a disease process. Modules may interact additively, synergistically, or antagonistically in any given individual. Multiple modules can coexist and produce unique disease phenotypes. We illustrate this concept with examples from the murine autoimmune model of type one diabetes, the nonobese diabetic (NOD) mouse.
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  • Brendan E Boyce, Ping Li, Zhenqiang Yao, Qian Zhang, I. Raul Badell, E ...
    2005 Volume 54 Issue 3 Pages 127-131
    Published: 2005
    Released: June 20, 2006
    JOURNALS FREE ACCESS
    Chronic inflammatory bone diseases, such as rheumatoid arthritis, periodontal disease and aseptic periprosthetic osteolysis, are characterized by bone loss around affected joints and teeth caused by increased osteoclastic bone resorption. This resorption is mediated largely by the increased local production of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNFα). These cytokines may induce resorption indirectly by affecting the production of the essential osteoclast differentiation factor, receptor activator of NF-κB ligand, and/or its soluble decoy receptor, osteoprotegerin, by osteoblast/stromal cells or directly by enhancing proliferation and/or activity of cells in the osteoclast lineage. The importance of TNFα in the pathogenesis of various forms of bone loss is supported by both experimental and clinical evidence. However, TNFα is not absolutely required for osteoclastogenesis, erosive arthritis, or osteolysis, as all these events could occur in the absence of TNFα and whether TNFα promotes osteoclast formation independently of RANK signaling is still a topic of debate. Here we review our current understanding of the mechanisms whereby TNFα increases osteoclastogenesis in vitro and in vivo.
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  • Brian M Strem, Kevin C Hicok, Min Zhu, Isabella Wulur, Zeni Alfonso, R ...
    2005 Volume 54 Issue 3 Pages 132-141
    Published: 2005
    Released: June 20, 2006
    JOURNALS FREE ACCESS
    Tissue engineering offers considerable promise in the repair or replacement of diseased and/or damaged tissues. The cellular component of this regenerative approach will play a key role in bringing these tissue engineered constructs from the laboratory bench to the clinical bedside. However, the ideal source of cells still remains unclear and may differ depending upon the application. Current research for many applications is focused on the use of adult stem cells. The properties of adult stem cells that make them well-suited for regenerative medicine are (1) ease of harvest for autologous transplantation, (2) high proliferation rates for ex vivo expansion and (3) multilineage differentiation capacity. This review will highligh the use of adipose tissue as a reservoir of adult stem cells and draw conclusions based upon comparisons with bone marrow stromal cells.
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  • Lorraine B. Ware, Julie A. Bastarache, Ling Wang
    2005 Volume 54 Issue 3 Pages 142-149
    Published: 2005
    Released: June 20, 2006
    JOURNALS FREE ACCESS
    Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common, life-threatening causes of acute respiratory failure that arise from a variety of local and systemic insults. The need for new specific therapies has led a number of investigators to examine the role of altered coagulation and fibrinolysis in the pathogenesis of ALI/ARDS. This review summarizes our current understanding of coagulation and fibrinolysis in human ALI/ARDS with an emphasis on pathways that could be potential therapeutic targets including the tissue factor pathway, the protein C pathway and modulation of fibrinolysis via plasminogen activator inhibitor-1. The available data suggest that clinical ALI and ARDS are characterized by profound alterations in both systemic and intra-alveolar coagulation and fibrinolysis. Fibrin deposition in the airspaces and lung microvasculature likely results from both activation of the coagulation cascade and impaired fibrinolysis, triggered by inflammation. Modulation of fibrin deposition in the lung through targeting activation and modulation of coagulation as well as fibrinolysis may be an important therapeutic target in clinical ALI/ARDS that deserves further exploration.
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ORIGINAL ARTICLE
  • Ryota Deshimaru, Ken Ishitani, Kazuya Makita, Fumi Horiguchi, Shiro No ...
    2005 Volume 54 Issue 3 Pages 150-155
    Published: 2005
    Released: June 20, 2006
    JOURNALS FREE ACCESS
    In the present study, the fatty acid composition of bone marrow aspirates and serum phospholipids in nine patients with hematologic diseases was investigated, and the effect of fatty acids on osteoblast differentiation in ST2 cells was examined. The concentrations of oleic acid and palmitic acid were significantly higher in bone marrow aspirates than in serum phospholipids, but the concentrations of other fatty acids did not differ. The rate of alkaline phosphatase positive ST2 cells induced by BMP-2 was significantly increased by oleic acid, but was unaffected by the presence or absence of palmitic acid. We conclude that the fatty acid composition of bone marrow aspirates differs from that of serum phospholipids. This difference may affect osteoblast differentiation in the bone marrow microenvironment.
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