Hirosaki Medical Journal
Online ISSN : 2434-4656
Print ISSN : 0439-1721
Volume 61 , Issue 1
Showing 1-7 articles out of 7 articles from the selected issue
Original Article
  • Yukihiro Itabashi, Toshiaki Baba, Satoru Kato, Kenichi Hakamada
    2010 Volume 61 Issue 1 Pages 1-7
    Published: 2010
    Released: August 17, 2021
    JOURNAL FREE ACCESS
        Forty patients with an average age of 64.6 years (range: 45-83) with early gastric cancer of cT1 (M, SM) underwent a curative-intended laparoscopy-assisted distal gastrectomy (LADG) where laparoscopic D1+α nodal clearance and extra-abdominal Billroth-I stapled anastomosis were performed. There was no conversion to open gastrectomy. The operation time for the 40 cases ranged 150 - 482 min (median: 285), while that for the latest 10 cases reduced to 154-278 min (median: 216). The length of hospital stay of the patients varied 10-85 days (median: 17). Postoperative complications encountered were anastomosis-related: 2 anastomotic bleeding and 2 anastomotic passage disturbance (1 stricture and 1 temporary stenosis) occurred but no dehiscence. Four inaccurate preoperative diagnoses of tumor invasion depth were revealed by postoperative pathology of the resected specimens. Thereafter the accuracy in the preoperative diagnosis was highly enhanced with implementation of endoscopic ultrasound. Recurrence occurred in one patient with pT2 (SS) pN2, who died of pleural carcinomatosis 4 years and 3 months after surgery.
        As the reduced operation time in LADG came closer to that in open distal gastrectomy, we will continue this procedure for early gastric cancer. For this, the importance of an accurate preoperative diagnosis can't be overemphasized.
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  • Ikko Yoshida, Hiroshi Ishizaka, Kazushi Hasegawa, Kiyohiko Satoh, Tomo ...
    2010 Volume 61 Issue 1 Pages 8-18
    Published: 2010
    Released: August 17, 2021
    JOURNAL FREE ACCESS
    Objectives: The purpose of this study was to test the hypothesis that adenosine-induced coronary microvascular dilation is blunted in the animals with diabetes mellitus (DM) through the impairment of KATP channel function.
    Background: Adenosine-induced coronary vasodilation is demonstrated to be mediated by activation of ATP-sensitive potassium (KATP) channels and nitric oxide (NO).
    Methods: The hearts of Otsuka Long-Evans Tokushima fatty rats (OLETF, type 2 DM rats), and control Long-Evans Tokushima fatty rats (LETO) at the ages of 32 and 8 weeks were perfused using a Langendorff system with constant perfusion pressure (80 mmHg). Changes in coronary flow to adenosine, pinacidil and sodium nitroprusside (SNP) were examined before and after administration of glibenclamide (10⁻⁷ M), or NG-nitro-L-arginine methyl ester (L-NAME, 10⁻⁴ M).
    Results: At the age of 32 weeks, adenosine- and pinacidil-induced increases in coronary flow were blunted in OLETF as compared with those in LETO (both p<0.05). Glibenclamide attenuated adenosine-induced increase in coronary flow in LETO (p<0.05), but not in OLETF. In contrast, L-NAME attenuated adenosine-induced increase in coronary flow in OLETF (p<0.05), but not in LETO. SNP-induced increases in coronary flow in LETO and OLETF were comparable and were not affected by glibenclamide. In 8-week-old OLETF and LETO, no difference was observed in adenosine-, pinacidil- and SNP-induced increases in coronary flow between OLETF and LETO.
    Conclusions: In this type 2 DM model, KATP channel function in coronary microcirculation is impaired. Adenosine-induced increase in coronary flow is mediated mainly by NO mechanism.
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  • Takemichi Sutoh, Ikuo Fukuda, Daisuke Kimura, Takao Tsushima
    2010 Volume 61 Issue 1 Pages 19-25
    Published: 2010
    Released: August 17, 2021
    JOURNAL FREE ACCESS
        Nafamostat mesilate (FUT-175), a synthetic serine protease inhibitor, has been reported to have antitumour activities toward solid tumours. The objective of this study was to characterize the biological activities of FUT-175 in a malignant mesothelioma cell line. We used MSTO-211H, a biphasic-type human malignant pleural mesothelioma cell line. The effect on cell growth was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Secretion of urokinase-type plasminogen activator (u-PA) and plasminogen activator inhibitor-1 (PAI-1) was analyzed by enzyme-linked immunosorbent assay. The effects on relative mRNA expression levels were measured by reverse transcription polymerase chain reaction. The effect on cell invasiveness was evaluated by cell invasion assay. FUT-175 at 10⁻⁵M significantly inhibited cell growth and cell invasiveness. Cell growth reduced to 47.0 ± 2.1% compared with the control. The number of invasive cells also reduced to 16.0 ± 0.7 cells/hpf, while that of control cells was 41.4 ± 8.0 cells/hpf. U-PA and PAI-1 secreted from the cells were also reduced by FUT-175 in a dose-dependent manner. These results suggest that FUT-175 has the potential to act as a therapeutic agent against local growth and invasion, and functions by reducing PAI-1 and u-PA production of the human malignant mesothelioma.
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  • Tatsuya Nodagashira, Hiroki Odagiri, Shojiro-Kazunori Ikenaga, Masaki ...
    2010 Volume 61 Issue 1 Pages 26-34
    Published: 2010
    Released: August 17, 2021
    JOURNAL FREE ACCESS
        Tissue-specific promoter has been used for cancer-specific suicide gene therapy, but its transcriptional activity is relatively low. For more efficient gene therapy of HER2-expressing tumor, a double adenovirus infection system was established, in which a ‘regulator’ vector carried Cre gene under the control of HER2 promoter and ‘target’ vectors carried target genes activated by Cre. We constructed a Cre recombinase expression vector, AxHER2Cre, for the ‘regulator’ vector. By the combination of this vector and AxCALNLZ, β-D-galactosidase was induced in 90% and 70% of MKN7 and MDA-MB-453, HER2‒overexpressing cell lines, but only about 20% and 10% of MKN28 and MCF7, low HER2-expressing cell lines. By the quantification analysis, the β-galactosidase activities induced by this system were comparable to those by the combination of AxCANCre and AxCALNLZ. These results indicated that Cre/loxP system under the regulation of HER2 promoter could induce efficient gene expression, maintaining the HER2-expression specificity. Breast cancer with HER2 overexpression is treated with trastuzumab. However, refractory or resistance of HER2 positive breast cancer against trastuzumab becomes a severe clinical problem, recently. This system seemed to be another therapeutic option.
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  • Hideaki Sato, Masashi Sato, Makie Chiba, Kyoko Ito, Koichi Ito
    2010 Volume 61 Issue 1 Pages 35-45
    Published: 2010
    Released: August 17, 2021
    JOURNAL FREE ACCESS
        The ability of murine allogeneic umbilical cord blood cells (UCBCs) to reconstitute the immune system was investigated. UCBCs obtained from fetuses of C57BL/6 (B6; H-2b) mice, which were transgenic for green fluorescent protein (GFP), were transplanted into RAG2 (-/-) BALB/c mice (H-2d). After transplantation, flow cytometric analysis revealed successful reconstitution of phenotypically mature GFP-positive immune cells of donor origin, including T cells, B cells, monocytes, and granulocytes in the peripheral blood of the recipient mice. Analysis of functional maturation of lymphocytes revealed that 2,4,6-trinitrophenyl-keyhole limpet hemocyanin (TNP-KLH)-immunized UCBC-transplanted recipients produced both TNP-specific IgM and IgG antibodies. These results indicated that the recipient mice were capable of mounting antibody responses to T-dependent antigens; further, Ig class switching from IgM to IgG confirmed that both B cells and CD4⁺ helper T cells derived from allogeneic UCBCs were immunologically competent. Furthermore, mice transplanted with allogeneic UCBCs accepted skin grafts from both B6 and BALB/c mice. However, these chimeric mice completely rejected skin grafts from third party C3H/HeJ (H-2k) mice, indicating the presence of functional CD8⁺ killer T cells as well as CD4⁺ helper T cells. In terms of potential clinical application, our results indicate that allogeneic UCBC transplantation can enable recovery of the normal immune system in recipients.
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  • Kyoko Ito, Kazutaka Masuko, Koichi Ito
    2010 Volume 61 Issue 1 Pages 46-57
    Published: 2010
    Released: August 17, 2021
    JOURNAL FREE ACCESS
        Contact between dendritic cells (DCs) and resting T cells is essential for initiation of the primary immune response. In this study, we examined whether neuronal leucine-rich repeat protein 3 (NLRR3), a receptor involved in nerve system development, participates in DC-T cell binding and T-cell activation. We confirmed that NLRR3 is expressed on naive T cells. NLRR3 contains an Arg-Gly-Asp (RGD) motif in its amino acid sequence, for which several integrins can be considered as potential ligands. Indeed, monocyte-derived DCs expressed several integrins that can bind to the RGD motif. Functionally, DC-induced resting allogeneic T-cell proliferation was partially inhibited by addition of integrin-specific antibodies and synthetic RGD peptides, indicating that RGD-containing molecules, including NLRR3 and several integrins, at least participate in the events of the initial primary immune response involving naive T cells and DCs. Furthermore, DCs were shown to bind directly to NLRR3-transfected Chinese hamster ovary cells in a NLRR3-dependent manner, and the binding was removed in the presence of integrin-specific antibodies. These data suggest that NLRR3 plays an important role in initiation of the primary immune response.
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  • Hiroaki Yokoyama, Shin Saito, Takumi Higuma, Hiroyuki Hanada, Tomohiro ...
    2010 Volume 61 Issue 1 Pages 58-64
    Published: 2010
    Released: August 17, 2021
    JOURNAL FREE ACCESS
        Adipose tissue secretes various bioactive molecules (adipokines), and apelin is one kind of adipokines. Recently, it was shown that plasma apelin level is decreased in patients with chronic heart failure, and apelin might play an important role in the pathogenesis of cardiovascular disease. However, plasma apelin level in coronary artery disease (CAD) or other heart disease such as valvular heart disease (VHD) has not been elucidated. We enrolled 31 patients with CAD and 14 patients with VHD who underwent elective cardiac surgery. We also examined plasma apelin level in 20 healthy subjects (Control). Blood samples were obtained before the surgery. Paired samples of visceral and subcutaneous adipose tissues were harvested during surgery. Plasma apelin level was lower in both CAD and VHD than in Control. When compared between CAD and VHD, it was lower in CAD than in VHD, and was not affected by treatment with HMG-CoA reductase inhibitors (statins) which was shown to increase adiponectin level. Left ventricular ejection fraction (LVEF) was lower in CAD than in VHD. There was no correlation between plasma apelin level and LVEF. Gene expression of apelin in visceral adipose tissue was higher than that in subcutaneous adipose tissue, but it was similar between two groups. These suggest that plasma apelin level was decreased in patients with cardiac diseases, especially in those with CAD. Its role in the pathophysiology of CAD remains to be elucidated.
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