Juntendo Medical Journal
Online ISSN : 2188-2134
Print ISSN : 0022-6769
ISSN-L : 0022-6769
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Volume 56, Issue 4
Displaying 1-14 of 14 articles from this issue
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Contents
  • The Role of the Notch3 Signaling Pathway in the Pathogenesis of Atherosclerosis
    TETSURO MIYAZAKI
    2010 Volume 56 Issue 4 Pages 306-313
    Published: August 31, 2010
    Released on J-STAGE: November 21, 2014
    DOIhttps://doi.org/10.14789/pjmj.56.306
    JOURNAL FREE ACCESS
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    Notch signaling pathway, which determines cell growth, differentiation and apoptosis, also mediates inflammatory responses in macrophages. Of the 4 Notch receptors (Notch1-4), Notch3 expression is selectively increased during macrophage differentiation. Whether Notch3 mediates macrophage activation and promotes cardiometabolic disorders in vivo remains unknown. We established a macrophage-selective Notch3 intercellular domain transgenic mouse (Notch3tg) under control of the macrophage SR-A promoter/enhancer. Peritoneal macrophages of Notch3tg showed a “classical” activating (M1) phenotype (i.e. increased IL-1β and iNOS expression and decreased arginase 1 expression) and increased expression of bone morphogenetic proteins (i.e. BMP-4 and -7), which have been implicated in osteoblast differentiation. To assess the roles of macrophage-selective notch3 signaling in obesity and atherosclerosis, we generated Notch3tgLdlr-/- (n=10) and Ldlr -/- littermates (n=10) and fed these animals a high fat and high cholesterol diet for 24 weeks. Peritoneal macrophages of Notch3tgLdlr -/- promoted foam cell formation with increased expression of scavenger receptors (i.e. CD36, SR-A and LOX-1). Notch3tgLdlr-/- increased lipid-rich plaque with macrophage accumulation and vascular calcification. Notch3tgLdlr-/- showed increased epididymal and subcutaneous fat weight. In epididymal fat, Notch3tgLdlr-/- showed increased expression of leptin consistent with visceral fat accumulation. In conclusion, Notch3 signaling in macrophages activates macrophage proinflammatory function and promotes obesity, atherosclerosis and vascular calcification.
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  • Induction of Immunotolerance in Organ Transplantation
    TOSHIYASU KAWAHARA
    2010 Volume 56 Issue 4 Pages 314-320
    Published: August 31, 2010
    Released on J-STAGE: November 21, 2014
    DOIhttps://doi.org/10.14789/pjmj.56.314
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    Rejection of MHC-mismatched graft is the main barrier to successful transplantation. Improvement of immunosuppressive medications has allowed transplanted organs to be accepted for a longer term. However, long-term immunosuppression increases the incidence of infections and malignancy. Induction of donor-specific tolerance would avoid both chronic graft rejection and the side effects associated with chronic and nonspecific immunosuppressive therapy. This would be the ultimate goal of immunosuppression for patients undergoing organ transplantation. Numerous experimental studies have demonstrated the induction of immunotolerance in rodent models, but there are some barriers to extend those protocols to large animal models and to human clinical applications. Among these barriers, mixed chimerism induced by bone marrow transplantation is an effective therapy to induce tolerance of T cells, B cells and NK cells in both allogeneic and xenogeneic combinations. This review will focus on how mouse studies have facilitated our understanding of the mechanisms underlying immunotolerance, and summarizes the major findings to highlight the mixed chimerism induced by bone marrow transplantation, costimulation blockade and regulatory T cells.
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  • Are Carcinoma-associated Fibroblasts a Key Therapeutic Target?
    AKIRA ORIMO
    2010 Volume 56 Issue 4 Pages 321-327
    Published: August 31, 2010
    Released on J-STAGE: November 21, 2014
    DOIhttps://doi.org/10.14789/pjmj.56.321
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    Carcinoma is a complex tissue that consists of carcinoma cells and various types of recruited stromal cells, notably myofibroblasts, fibroblasts, leukocytes, pericytes, and endothelial cells. Recent reports have indicated that these stromal cells provide significant physiologic support to the nearby carcinoma cells, suggesting that carcinoma cells initially recruit and/or activate these various stromal cells, and that the latter then reciprocate by fostering carcinoma cell proliferation and survival during the course of tumor progression. Carcinoma-associated fibroblasts (CAFs), frequently present in the stroma of various different human carcinomas, include a large number of myofibroblasts, a hallmark of activated fibroblasts. The presence of these cells in large numbers is also associated with higher-grade malignancy and poor prognosis in patient. The activated myofibroblast state of stromal fibroblasts also correlates with their ability to promote tumor growth. This review highlights the biological role of the tumour-associated stroma, with a particular focus on myofibroblasts and their ability to promote tumour progression through their interactions with carcinoma cells.
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  • Recent Views on Palliative Care and Loss Simulation
    HARUYUKI KASUDA, SATOSHI MIYAKE, YOSHIKO OZAWA, RUI KANO, KEI SAITO, Y ...
    2010 Volume 56 Issue 4 Pages 328-333
    Published: August 31, 2010
    Released on J-STAGE: November 21, 2014
    DOIhttps://doi.org/10.14789/pjmj.56.328
    JOURNAL FREE ACCESS
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    1. Recent views on palliative care Unlike in the West, palliative care in Japan started in hospitals. About 200 hospices/palliative care wards have been founded in Japan. However, without a culture and history highly valuing hospices like in the West, and in an environment which makes it hard for home-based hospice care to evolve, palliative care in Japan, which started in hospitals, has tended to remain there. In Japan's aging society, in which the rate of death from cancer is ever increasing, hospitals will sooner or later reach capacity, resulting in the emergence of “terminal cancer refugees”. Under these circumstances, the “Cancer Control Act” was enacted in April 2007, stipulating “palliative care for pain shall be available early in the course of an illness as required”, “cooperative systems for providing medical care for cancer at home shall be established”, and “the opportunities for health care providers to receive training in palliative care shall be ensured” to “improve patients' quality of life”. Since 2009, the Ministry of Health, Labour, and Welfare has obliged all regional cancer centers to hold a “palliative care workshop” for about 12 hours over 2 days to “provide basic palliative care education for all cancer care doctors”. However, it is likely to take 5 to 10 years for all cancer care doctors to fully attend the workshop. New efforts to facilitate home-based palliative care and regional cooperation have been led by doctors at clinics and the Japan Medical Association in a number of places, such as Natori-shi in Miyagi Prefecture, Onomichi-shi in Hiroshima Prefecture, and Nagasaki-shi in Nagasaki Prefecture. In Tochigi Prefecture, “Palliative Home Care Tochigi” was founded 2 years ago, and is working to establish a network for regional cooperation. 2.Spiritual pain and “loss simulation” What do we experience mentally in the course of dying? The mental pain of patients who have realized that they cannot be cured and their days are numbered is beyond the understanding of other people. Over the course of losing what is important to them and becoming unable to perform various activities, patients are compelled to change their daily lives and ask themselves questions, such as “what is really important?” and “what have I lived for?”, and agonize over them. This is the “spiritual pain” that shakes one's identity to its foundations.
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  • The Current Status of Sepsis Research in Japan in Comparison to the Status of International Research
    SHIORI KAWASAKI, TOSHIAKI IBA
    2010 Volume 56 Issue 4 Pages 334-338
    Published: August 31, 2010
    Released on J-STAGE: November 21, 2014
    DOIhttps://doi.org/10.14789/pjmj.56.334
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    The current trend in sepsis treatment follows international guidelines. However, the contribution of Japan to these guidelines has been quite limited. In contrast to the increase in the number of publications from the other countries, the number of publications from Japan has shown a tendency to decrease in recent years. Sepsis research in Japan comprises a comparatively small percentage of human studies. Especially, the limited number of randomized controlled trial is a problem. Since an increase in the quality of Japanese research has been estimated from recent journal rankings, it is suggested that we can contribute to the production of international guidelines more efficiently by performing infrastructural preparation that can provide high quality clinical research such as large-scale multi-institutional studies.
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  • In vitro Efficacy of Arbekacin and Sulbactam/Ampicillin in Combination to Inhibit Occurrence of Staphylococcus aureus Small Colony Variants
    EIJI TOMINAGA, TERUYO ITO, VON EIFF CHRISTOF, KEIICHI HIRAMATSU
    2010 Volume 56 Issue 4 Pages 339-349
    Published: August 31, 2010
    Released on J-STAGE: November 21, 2014
    DOIhttps://doi.org/10.14789/pjmj.56.339
    JOURNAL FREE ACCESS
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    Objective : To examine whether small colony variants (SCVs) would occur in the Staphylococcus aureus (S.aureus) population when they were cultivated with arbekacin (ABK), and to know the efficacy of the use of ABK in combination with sulbactam/ampicillin (SBT/ABPC) for the prevention of the occurrence of SCVs. Materials and Methods : Fractional Inhibitory Concentration (FIC) indices of ABK and SBT/ABPC were determined with macrobroth dilution method recommended by Clinical and Laboratory Standards Institute (CLSI) with six S. aureus strains (a MSSA strain, a MRSA strain, and four VISA strains). The number of viable cells and the ratio of SCVs among them were estimated by inoculating serially diluted culture. The bactericidal effect of the combination use of two drugs to SCVs-rich culture was examined further by estimating the number of viable cells and ratio of SCVs in the culture. Results : SCVs occurred in all S. aureus strains so far examined when cultured with ABK alone, but both numbers of viable cells and the ratio of SCVs among them were reduced with ABK and SBT/ABPC in combination, which showed good bactericidal activity to SCVs-rich culture. Conclusions : We re-evaluated the efficacy of ABK and SBT/ABPC in combinationm which could reduce the occurrence of SCVs with ABK. We suggest that combination therapy with ABK and SBT/ABPC would be recommended for MRSA infection.
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  • Efficiency of 23 Gauge Vitrectomy Performed by Four Sclera Ports System with Chandelier Endoillumination
    Comparison with 23 Gauge Vitrectomy Performed by Three Sclera Ports System
    MOMOKO HIMI, DAISUKE KUDO, TOSHIRO FUJIMAKI, TOSHIYUKI YOKOYAMA
    2010 Volume 56 Issue 4 Pages 350-353
    Published: August 31, 2010
    Released on J-STAGE: November 21, 2014
    DOIhttps://doi.org/10.14789/pjmj.56.350
    JOURNAL FREE ACCESS
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    We compared the surgical duration and rates of intra- and postoperative complications between the three scleral port system and four scleral port system with chandelier endoillumination in 23-gauge (23G) vitrectomy for proliferative diabetic retinopathy and retinal detachment in order to estimate the safety of the four scleral port system. Thirty-three cases were managed by the three scleral port system, while 19 cases were managed by the four scleral port system. There were no apparent differences in either surgical duration or the rates of intra- and postoperative complications.
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