The Keio Journal of Medicine
Online ISSN : 1880-1293
Print ISSN : 0022-9717
ISSN-L : 0022-9717
Volume 60, Issue 2
Displaying 1-4 of 4 articles from this issue
  • Taketo Yamada
    2011 Volume 60 Issue 2 Pages 37-46
    Published: 2011
    Released on J-STAGE: July 03, 2011
    JOURNAL FREE ACCESS
    Over a hundred years has passed since the discovery of the "magic bullet" serum therapy by Kitasato and Behring, the first ever therapeutic use of antibodies. More than 80 years later, the investigation of immunoglobulin structure and function and the development of cell and molecular biology introduced the production of monoclonal antibodies (MoAbs). In the 35 years since the first process for creating MoAbs was introduced, they have remained the centerpiece of the growing biotechnology and pharmaceutical industry. Herein, I review the history, development, and clinical settings of therapeutic MoAbs that have had a significant impact on life-saving medicine.
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  • Hideaki Nakajima
    2011 Volume 60 Issue 2 Pages 47-55
    Published: 2011
    Released on J-STAGE: July 03, 2011
    JOURNAL FREE ACCESS
    Differentiation of hematopoietic cells is a sequential process of cell fate decision originating from hematopoietic stem cells (HSCs), allowing multi- or oligopotent progenitors to commit to certain lineages. HSCs are cells that are able to self-renew and repopulate the marrow for the long term. They first differentiate into multipotent progenitors (MPPs), which give rise to common lymphoid progenitors (CLPs) and common myeloid progenitors (CMPs). CMPs then differentiate into granulocyte monocyte progenitors (GMPs) and megakaryocyte erythroid progenitors (MEPs), which are the precursors of granulocytes/monocytes and erythrocytes/megakaryocytes, respectively. Lineage specification at differentiation branch points is dictated by the activation of lineage-specific transcription factors such as C/EBPα, PU.1, and GATA-1. The role of these transcription factors is generally instructive, and the expression of a single factor can often determine cell fate. Differentiation was long regarded as an irreversible process, and it was believed that somatic cells would not change their fate once they were differentiated. This paradigm was first challenged by the finding that ectopic cytokine signals could change the fate of differentiation, probably through modulating internal transcription networks. Subsequently, we and others showed that virtually all progenitors, including CLPs, CMPs, GMPs, and MEPs, still retain differentiation plasticity, and they can be converted into lineages other than their own by ectopic activation of only a single lineage-specific transcription factor. These findings established a novel paradigm for cellular differentiation and opened up an avenue for artificially manipulating cell fate for clinical use .
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  • Satoshi Takahashi, Kazunari Yoshida, Takeshi Kawase
    2011 Volume 60 Issue 2 Pages 56-64
    Published: 2011
    Released on J-STAGE: July 03, 2011
    JOURNAL FREE ACCESS
    In this report, we review 41 patients with intracranial germ cell tumors (GCTs) treated at the Department of Neurosurgery, Keio University School of Medicine, in the 25-year period between January 1982 and July 2006. The main aim of the present study was to compare the effectiveness of our current intracranial GCT management protocol, comprising neoadjuvant chemo-radiotherapy without surgical biopsy of tumors as far as possible, to that of historical controls. In all patients, charts were reviewed and tumor and patient characteristics, including age, sex, type of tumor marker secreted, treatment protocol, and clinical outcomes, were compared. The relationship between these variables was analyzed by means of the Cox proportional hazards model. Thus far, four patients treated by approaches other than the current protocol have died of their tumor. The overall 5-, 10-, and 15-year survival rates of all the patients calculated by the Kaplan-Meier method were 91.9%, 88.6%, and 88.6%, respectively. According to the results of the Cox proportional hazards model, patients with secreting GCTs show statistically poorer prognoses than those with non-secreting GCTs (P = 0.0073), and although not statistically significant, patients treated with our current protocol tend to show better prognoses than historical controls (P = 0.0543). All five patients with secreting GCT treated using our current protocol are still alive after an average follow-up period exceeding 7 years, and only one of these has shown tumor recurrence. With our current treatment protocol comprising neoadjuvant chemo-radiotherapy without surgical biopsy, prognoses of patients with GCTs have improved compared to historical controls at our institution.
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  • Peter B. Ernst, Elizabeth B. Wiznerowicz, Sandford H. Feldman, Kenneth ...
    2011 Volume 60 Issue 2 Pages 65-68
    Published: 2011
    Released on J-STAGE: July 03, 2011
    JOURNAL FREE ACCESS
    Inflammatory bowel disease is a chronic inflammatory disease of the gut which manifests as ulcerative colitis or Crohn's disease. One of the most studied animal models of spontaneous Crohn's disease is the senescence-accelerated mouse (SAMP1/Yit strain) model. In SAMP1/Yit mice, although many immunological responses are perturbed, some evidence suggests that the primary defect lies in the epithelial cell barrier. In the process of studying epithelial permeability, we observed that the stomach in SAMP1/Yit mice also had increased permeability. Upon further examination, these mice were shown to have marked, chronic gastritis with focal to diffuse aggregates of mononuclear cells of mixed lineages. These aggregates were located predominantly in the oxyntic mucosa, with occasional lesions in the forestomach but with relatively fewer cellular infiltrates in the antral mucosa. Real-time RT PCR showed an increase in several helper T cell (Th cell)-derived pro-inflammatory cytokines in the gastric mucosa of SAMP1/Yit mice. However, many of the cells in the aggregates of SAMP1/Yit mice were B cells. SAMP1/Yit B cells exacerbate ileitis when co-transferred into immunodeficient recipients. The gastritis also reflects a contribution by B cells. As SAMP1/Yit mice were derived from AKR mice, we examined AKR mice and determined that they too have an increased occurrence of gastritis, although they do not develop ileitis. B cells contributed to the gastric inflammation in these mice also. Thus, SAMP1/Yit mice display gastritis as well as ileitis, and B cells appear to play a role in the pathogenesis of inflammation at both sites. This review will discuss some of the mechanisms that may account for these different manifestations of gastrointestinal disease.
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