The Keio Journal of Medicine
Online ISSN : 1880-1293
Print ISSN : 0022-9717
ISSN-L : 0022-9717
Volume 60, Issue 1
Displaying 1-4 of 4 articles from this issue
COMMEMORATIVE LECTURE
  • Jeffrey M. Friedman
    2011 Volume 60 Issue 1 Pages 1-9
    Published: March 25, 2011
    Released on J-STAGE: April 05, 2011
    JOURNAL FREE ACCESS
    The cloning of the ob gene and its gene product, leptin, has led to the elucidation of a robust physiologic system that maintains fat stores at a relatively constant level. Leptin is a peptide hormone secreted by adipose tissue in proportion to its mass. Recessive mutations in the leptin gene are associated with massive obesity in mice and humans, establishing a genetic basis for obesity. Leptin circulates in blood and acts on the brain to regulate food intake and energy expenditure. When fat mass falls, plasma leptin levels fall, stimulating appetite and suppressing energy expenditure until fat mass is restored. When fat mass increases, leptin levels increase, suppressing appetite until weight is lost. This system maintains homeostatic control of adipose tissue mass. The discovery of leptin has advanced our understanding of metabolic disease in a number of respects. Its identification has revealed a new endocrine system regulating body weight. This system provides a means by which changes in nutritional state regulate other physiologic systems. A number of leptin deficiency syndromes that are treatable with leptin replacement have been identified. The majority of obese subjects are leptin resistant, which establishes that obesity is the result of hormone resistance. Leptin treatment results in weight loss in a subset of obese patients and can also synergize with other anti-obesity agents to reduce weight in the general population. Leptin provides an entry point for studying a complex human behavior. Finally, this research has established that there is a powerful biological basis for obesity, a fact that is (correctly) changing public perception about the pathogenesis of this medical condition.
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REVIEW
  • Yves Renaudineau, Pierre Youinou
    2011 Volume 60 Issue 1 Pages 10-16
    Published: March 25, 2011
    Released on J-STAGE: April 05, 2011
    JOURNAL FREE ACCESS
    Epigenetics signifies stable and heritable changes in gene expression without changes in the genetic code. There is a wealth of emerging evidence for such processes in promoting autoimmunity. The first clue is that inhibition of DNA methyl transferases (DNMTs) induces systemic lupus erythematosus (SLE) in animals. Similar immune-mediated disorders have been generated by injecting normal T cells incubated with DNMT inhibitors into healthy mice. Further, monozygotic twins display differences in DNA methylation that parallel discordances in SLE. Moreover, defects in DNA methylation characterize lymphocytes from SLE, synoviocytes from rheumatoid arthritis, and neural cells from multiple sclerosis patients. It has also been shown that DNA hypomethylation of T and B cells correlates with reduced DNMT efficacy and histone acetylation in SLE. Once a gene promoter has been demethylated, the gene recovers its capacity to be transcribed, e.g., genes for cytokines, activation receptors on cells, and endogenous retroviruses. This outcome has been associated with a blockage of the Erk pathway and/or a growth arrest at the G0/G1 interface of the cell cycle. Of importance is the fact that these changes can be reversed. For example, blockade of the interleukin-6 autocrine loop in SLE B cells restores DNA methylation status, thus opening new perspectives for therapy.
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ORIGINAL ARTICLE
  • Hiroto Terashi, Ikuro Kitano, Yoriko Tsuji
    2011 Volume 60 Issue 1 Pages 17-21
    Published: March 25, 2011
    Released on J-STAGE: April 05, 2011
    JOURNAL FREE ACCESS
    Treatment must be conducted after proper assessment of diabetic foot wounds. This implies appropriate foot care and the use of proper footwear from the perspectives of prophylaxis and walking. Diabetic foot wounds have some wound impairment factors, including peripheral neuropathy (PN), peripheral arterial disease (PAD), and infection; such wounds comprise combinations of these lesions. An additional goal besides wound healing is gait salvage. Here, we propose a simple new four-level classification of diabetic foot ulcerations, which we have termed the Kobe classification, in order to assess the wounds more easily and treat them systematically; the classification is as follows: Type I, mainly PN; Type II, mainly PAD; Type III, mainly infection; Type IV, PN+PAD+infection.
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LECTURE
  • Chusuke Nishio
    2011 Volume 60 Issue 1 Pages 22-26
    Published: March 25, 2011
    Released on J-STAGE: April 05, 2011
    JOURNAL FREE ACCESS
    This article discusses the inception (in 1955) and history of the inclusion of the summary mental examination in criminal proceedings. It then reviews the procedures for diagnosing easily diagnosed cases such as frank psychosis or obvious mental normality. An overview is then provided of the manner in which the reliability of the summary examination can be maintained by deeming those cases where diagnosis can be made without the use of suggestive questions as “easily diagnosed cases”and by avoiding positively diagnosing obvious mental normality. The importance of ensuring that test proceedings in summary examinations do not interfere with formal forensic psychiatric examinations that may be conducted later is then reviewed. These proceedings, through the summary examination, provide material for an expert to state an opinion in court as to the criminal responsibility of the accused suspect.
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