Hirosaki Medical Journal
Online ISSN : 2434-4656
Print ISSN : 0439-1721
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Showing 1-23 articles out of 23 articles from the selected issue
  • Yasufumi Endo, Genn Takahashi, Ikuko Kakizaki, Masahiko Endo
    2019 Volume 70 Issue 1 Pages 1-12
    Published: 2019
    Released: December 05, 2019
    JOURNALS FREE ACCESS
    Abstract: Hyaluronan(HA)is a ubiquitous glycosaminoglycan comprising N-acetylglucosamine and glucuronic acid and is involved in matrix formation and cell maintenance. 4-Methylumbelliferone(MU)exhibits anti-tumor activities by inhibiting HA synthesis. In this study, we aimed to elucidate the association between HA and numerous matrix molecules.
    Materials and Methods: We created HA-knock down extracellular matrix(ECM)by culturing human skin fibroblasts(HSF)in the presence of MU(0.5 mM)for 3 days after confluence. Following culture in the presence or absence of MU, the cell layer and culture medium were collected and ECM molecules were measured using enzyme-linked immunosolvent assay, and the[35S]-sulfate uptake method.
    Results: Proteoglycans and type I collagen were released into the medium as HA decreased. However, type I collagen, but not proteoglycans, was immediately replenished. Fibronectin and CD44 in the cell layer decreased, but were not replenished, as HA decreased. On contrary, laminin, cadherin, and vitronectin were not affected by HA decrease.
    Conclusions: HA knockdown by MU treatment elucidated the dynamic interactions between HA and ECM components. Our findings suggest that HA interacts with other ECM components through various ways, including strong interactions for ECM network formation and loose interactions for signal transduction.
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  • Kaori Kubo, Ko Kudo, Tsutomu Toki, Rika Kanezaki, Fumika Ikeda, Tatsuy ...
    2019 Volume 70 Issue 1 Pages 13-23
    Published: 2019
    Released: December 05, 2019
    JOURNALS FREE ACCESS
    The causes for individual relapse in children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) remain incompletely understood. Here, we performed comprehensive genetic analyses of 20 pediatric BCP-ALL paired diagnosis-relapse samples. Copy number variation analysis of IKZF1, a gene for which deletions are associated with increased relapse risk, revealed deletions at both diagnosis and at relapse (n=5). Targeted next generation sequencing showed that RAS pathway genes including KRAS (n=4), NRAS (n=2) and PTPN11 (n=2) were the most common mutations among the sequencing targets at diagnosis and/or relapse. In 7 of 20 cases (35%), mutations in PTPN11, KRAS, TP53, CTCF, NCOR1, WHSC1, TUSC3, ERG and NT5C2   were detected only at relapse. Two cases with TP53   mutations showed fatal outcomes. In two of the four cases with high hyperdiploid BCP-ALL, associated with favorable prognosis, PTPN11 mutations were detected only at relapse. Targeted RNA sequencing identified a rare subtype of BCP-ALL with a NUP214-ABL1 fusion that could benefit from tyrosine kinase inhibitors. Together with recent reports that RAS mutations confer sensitivity to MEK inhibitors, these results suggest that comprehensive genetic analysis will contribute to the optimal treatment for relapsed BCP-ALL.
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  • Hidemi Yoshida, Yuko Hashimoto, Takashi Fukushima, Kunikazu Tanji, Tom ...
    2019 Volume 70 Issue 1 Pages 24-38
    Published: 2019
    Released: December 05, 2019
    JOURNALS FREE ACCESS
    Toxic amyloid-beta (Aβ) is known to generate symptoms of Alzheimer’s disease (AD); however, less is known regarding the neurotoxicity of Aβ at lower concentrations. Moreover, the neuroprotective potential of combination treatment with plant biophenols and existing drugs is not well understood. In this study, we estimated the no-observed adverse effect level (NOAEL) of Aβ 1–42 (Aβ42) against cultured human neuroblastoma SH-SY5Y cells, and examined the neuroprotective effect of combination pretreatment with 10 µM carnosic acid, 30 nM rebamipide, 10 µM edaravone, and 10 µM of resveratrol (the “CRER” blend) on weak but toxic Aβ42-treated SH-SY5Y cells. We evaluated the NOAEL of Aβ42 at 500 nM in these cells. Aβ42 at 1–8 µM reduced cell viability; however, the “CRER” blend ameliorated this Aβ42-induced decrease in viability. The “CRER” blend induced the expression of Aβ-degrading enzymes including matrix metalloproteinase-14 (MMP-14) and neprilysin, while also enhancing the expression of the inducible α-secretase TACE (tumor necrosis factor-α-converting enzyme), sirtuin 1 (SIRT1), and brain-derived neurotrophic factor (BDNF). Collectively, our results indicate that the “CRER” may aid in the prevention of Aβ toxicity by enhancing MMP-14, neprilysin, TACE, SIRT1, and BDNF. Thus, the “CRER” blend may prove to be a promising strategy for the prevention of Aβ-mediated disorders, particularly AD.
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  • Hiroshi Saito, Masashi Matsuzaka, Rina Tanaka, Yoshihiro Sasaki
    2019 Volume 70 Issue 1 Pages 39-46
    Published: 2019
    Released: December 05, 2019
    JOURNALS FREE ACCESS
    The aim of this study was to compare deviation of medical resources for colorectal cancer among secondary medical areas in Aomori prefecture. Prevalence of colorectal cancer as an indicator of medical demand, a number of specialist of gastrointestinal surgery, a number of bed in hospitals and a number of hospital per 100,000 residents, respectively, as indicators of medical supply were estimated. Deviation of medical resources were quantified by calculating Gini coefficient (GC) and Herfindahl-Hirschman Index (HHI). The GCs of the number of the specialist, the number of the bed and the number of hospital were 0.285, 0.115 and 0.053, respectively. The HHI of these were 2736, 2272 and 2102, respectively. In the medical resources, deviation of the number of the specialist was the largest in estimation using both GC and HHI. A mismatch between supply and demand in medical services for colorectal cancer was recognized, and deviation of the number of the specialist was the largest among them. To alleviate an influence of the mismatch, telemedicine and differentiation of a role in medical services for colorectal cancer among hospitals should be promoted.
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  • Shingo Terashima, Fumio Komai, Hiromu Sugawara, Yuka Takahashi, Naoki ...
    2019 Volume 70 Issue 1 Pages 47-55
    Published: 2019
    Released: December 05, 2019
    JOURNALS FREE ACCESS
    Commercial radiation treatment planning system (RTPS) cannot be used in total body irradiation (TBI) using long source-axis distance (SAD) in many cases, mainly due to the treatment distance outside RTPS specification. We have considered whether it is possible to determine the prescribed MU and the thickness of the compensators at SAD 350 cm, 400 cm, using data calculated at SAD 300 cm which is the limit of RTPS of our own facility. The dose characteristics at long SAD were acquired and corrections were made so that the calculation result of RTPS at SAD 300 cm would be the value measured under the condition of long SAD. The maximum difference between the MU of this method and the MU irradiated to the patient was 3.6%. We got a good result of thickness of the compensators calculated for the femur and lower leg showed, however the differences were greater in other parts. Although some improvement is necessary, it was suggested that the prescribed MU and the thickness of the compensators presumed using RTPS can be used for TBI setup.
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  • Madoka Fujita, Kentaro Yuzawa, Fumitake Miura, Tomomi Aizawa, Jun Shim ...
    2019 Volume 70 Issue 1 Pages 56-61
    Published: 2019
    Released: December 05, 2019
    JOURNALS FREE ACCESS
    Although Takayasu arteritis (TA) is rarely seen in children, difficult cases of childhood-onset TA have sometimes been reported. Recently, clinical efficacy of anti-proinflammatory cytokines treatment, including anti-interleukin-6 receptor antibody, tocilizumab (TCZ) has been reported in adult patients with refractory TA. However, only a few papers describing successful TCZ treatment in childhood onset TA has been reported to date. A 11-year-old girl complained of recurrent chest pain visited to a regional hospital. An echocardiography revealed aortic regurgitation and an electro-cardiogram revealed ST segment depression. Blood examinations revealed elevated serum C-reactive protein and troponin T. Various image inspection showed extended ascending aorta and stenosis of left coronary artery ostium, suggesting that she had probable TA. Initially, treatment with prednisolone (PSL), various immunosuppressants and anti-tumor necrosis factor α monoclonal antibody, infliximab was started. However, the disease activity could not be controlled. Then, after obtaining the approval of the ethic committee, an initiation of intravenous TCZ resulted in a rapid clinical remission in this patient. PSL was successfully tapered. Since her coronary angiogram showed 99% stenosis of left coronary artery ostium, coronary artery bypass grafting was successfully conducted thereafter. In our patient, treatment with TCZ was effective and safe including perioperative period. In the case of TA with high risk of organ damage, we believe that early initiation of TCZ would be necessary even in pediatric cases.
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  • Zaiqiang Yu, Norihiro Kondo, Xu Liu, Ikuo Fukuda
    2019 Volume 70 Issue 1 Pages 62-66
    Published: 2019
    Released: December 05, 2019
    JOURNALS FREE ACCESS
    An 80-year-old man with multilevel aortic aneurysms was referred to our hospital. Enhanced computed tomography showed a 90-mm descending aortic aneurysm and a 50-mm abdominal aortic aneurysm with severe stenosis of bilateral external iliac arteries. Thoracotomy was considered a high-risk procedure because he had a long history of chronic obstructive pulmonary disease. We performed combined operation; Y-graft replacement for making access routes, followed by thoracic endovascular aortic repair for the thoracic aortic aneurysm with one de-branching bypass from the left common carotid artery to the left subclavian artery. Neither paraplegia nor infectious complications occurred postoperatively.
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  • Zaiqiang Yu, Ikuo Fukuda, Norihiro Kondo, Masahito Minakawa, Kazuyuki ...
    2019 Volume 70 Issue 1 Pages 67-71
    Published: 2019
    Released: December 05, 2019
    JOURNALS FREE ACCESS
    A high percentage of patients with a unicuspid aortic valve require cardiac surgery, because it always induces aortic stenosis or regurgitation. It is sometimes difficult to discriminate it from a bicuspid valve. Here, we report a case of a young patient with severe aortic regurgitation and aortic root enlargement caused by the unicommissural form of unicuspid aortic valve. An aortic valve-sparing operation could not be performed because of his special morphology, and it was thought that sufficient durability could not be obtained postoperatively. The Bentall operation was successfully performed with a mechanical prosthetic valve. His postoperative course was uneventful.
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  • Naomi Kudo, Takahisa Abe, Shin Midorikawa, Atsushi Matsubara
    2019 Volume 70 Issue 1 Pages 72-76
    Published: 2019
    Released: December 05, 2019
    JOURNALS FREE ACCESS
    In recent years, anti-programmed cell death 1 (PD-1) antibody has been approved for recurrent/metastatic head and neck cancer and was reported by the phase 3 study ChackMate 141 to improve the overall survival rate of patients with recurrent/metastatic head and neck squamous cell carcinoma. With the increasing number of cases treated with anti-PD-1 antibody, the synergic interaction between cancer immunotherapy and chemotherapy has been gathering attention. Some reported that administration of chemotherapy after immunotherapy was remarkably effective for progressive non-small cell lung cancer. We examined two notable cases of recurrent/metastatic head and neck cancer in which the subsequent administration of chemotherapy after immunotherapy was markedly effective. The two cases included maxillary sinus cancer and laryngeal cancer that were treated with radiotherapy and chemotherapy as first-line treatment. Both cases developed recurrent/metastatic lesion that were treated with anti-PD-1 antibody. However, the lesions increased in size after immunotherapy. Therefore, subsequent chemotherapy with cetuximab and paclitaxel was considered and showed marked reduction of size of the recurrent/metastatic lesions. The two cases suggested that administration of salvage chemotherapy after immunotherapy is promising for recurrent/metastatic head and neck cancer.
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  • Arisa Asari, Tomomi Aizawa, Shojiro Watanabe, Koji Tsugawa, Hiroshi Ta ...
    2019 Volume 70 Issue 1 Pages 77-81
    Published: 2019
    Released: December 05, 2019
    JOURNALS FREE ACCESS
    We report an effective treatment with once-daily administration of cyclosporine A (CsA), an immunosuppressant which has been successfully treated the children with nephrotic syndrome (NS), of a boy with severe atopic dermatitis (AD). A 15-year-old boy with a history of AD suffered from repeated exacerbations (severity classification of 16/20) even he had been treated with a combination of betamethasone ointment and oral administration of prednisolone from the age of 10. According to the NS therapy, he was treated with once-daily preprandial administration of CsA with an initial dose of 1.3 mg/kg/day. Three weeks after the initial treatment of CsA, clinical condition was improved, and it was become possible to discontinue oral administration of prednisolone. At 2-hour post-dosing blood level of CsA was maintained at approximately 350 ng/ml, and no side effects were observed until 12 months after treatment. By this treatment method, the efficiency of CsA was obtained at lower doses compared to the recommended dose. Our results suggest that once-daily administration of CsA is one of the useful treatments for children with severe AD.
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  • [in Japanese]
    2019 Volume 70 Issue 1 Pages 82-84
    Published: 2019
    Released: December 05, 2019
    JOURNALS FREE ACCESS
    Download PDF (1144K)
  • [in Japanese]
    2019 Volume 70 Issue 1 Pages 85-87
    Published: 2019
    Released: December 05, 2019
    JOURNALS FREE ACCESS
    Download PDF (997K)
  • [in Japanese]
    2019 Volume 70 Issue 1 Pages 88-91
    Published: 2019
    Released: December 05, 2019
    JOURNALS FREE ACCESS
    Download PDF (1003K)
  • [in Japanese]
    2019 Volume 70 Issue 1 Pages 92-93
    Published: 2019
    Released: December 05, 2019
    JOURNALS FREE ACCESS
    Download PDF (994K)
  • [in Japanese], [in Japanese], [in Japanese], [in Japanese], [in Japane ...
    2019 Volume 70 Issue 1 Pages 94
    Published: 2019
    Released: December 05, 2019
    JOURNALS FREE ACCESS
  • [in Japanese], [in Japanese], [in Japanese], [in Japanese], [in Japane ...
    2019 Volume 70 Issue 1 Pages 94
    Published: 2019
    Released: December 05, 2019
    JOURNALS FREE ACCESS
  • [in Japanese], [in Japanese], [in Japanese], [in Japanese], [in Japane ...
    2019 Volume 70 Issue 1 Pages 94
    Published: 2019
    Released: December 05, 2019
    JOURNALS FREE ACCESS
  • [in Japanese], [in Japanese], [in Japanese], [in Japanese], [in Japane ...
    2019 Volume 70 Issue 1 Pages 95
    Published: 2019
    Released: December 05, 2019
    JOURNALS FREE ACCESS
  • [in Japanese], [in Japanese], [in Japanese], [in Japanese]
    2019 Volume 70 Issue 1 Pages 95
    Published: 2019
    Released: December 05, 2019
    JOURNALS FREE ACCESS
  • [in Japanese], [in Japanese]
    2019 Volume 70 Issue 1 Pages 95
    Published: 2019
    Released: December 05, 2019
    JOURNALS FREE ACCESS
  • [in Japanese], [in Japanese], [in Japanese], [in Japanese], [in Japane ...
    2019 Volume 70 Issue 1 Pages 96
    Published: 2019
    Released: December 05, 2019
    JOURNALS FREE ACCESS
  • [in Japanese], [in Japanese], [in Japanese], [in Japanese], [in Japane ...
    2019 Volume 70 Issue 1 Pages 96
    Published: 2019
    Released: December 05, 2019
    JOURNALS FREE ACCESS
  • [in Japanese], [in Japanese], [in Japanese], [in Japanese]
    2019 Volume 70 Issue 1 Pages 96
    Published: 2019
    Released: December 05, 2019
    JOURNALS FREE ACCESS
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