Toxic AGEs (TAGE) と健康：III. TAGEの構造とTAGEの分解機構

近年，終末糖化産物 (advanced glycation end-products, AGEs) は，生活習慣病 (lifestyle-related diseases, LSRD) の発症・進展に関与する重要な因子として注目されている。したがって，体内で生成されるAGEsの作用を抑えることが，病気の予防や治療において有効だと考えられている。しかし，AGEsは多様な構造を持ち，それぞれが異なる生物学的影響を及ぼすことが知られている。最近，筆者らはブドウ糖および果糖代謝の中間体であるglyceraldehyde (GA) から生成されるGA-AGEsの中でも細胞毒性の強いAGEs，すなわちtoxic AGEs (TAGE) がLSRDと強く関連していることを明らかにし，「TAGE原因説」を提唱している (金医大誌2023; 48: 1-11「TAGEと健康：I. 細胞障害因子としてのTAGE」参照)。血中TAGEレベルの上昇はLSRDの発症・進展に強く関連していることが示されており，TAGEが将来的な病気の発症・進展リスクを早期に予測するバイオマーカーとしての有用性を示唆している (金医大誌2023; 48: 12-21「TAGEと健康：II. LSRD予測マーカーとしてのTAGE」参照)。最近の研究では，TAGEが他のGA-AGEsとは異なる独自の構造を有することが推定された。本総説では，TAGE推定構造ならびにその内在性分解機構の概要について述べる。journal articl

哺乳類から検出した2種類の寄生虫の形態学的・遺伝学的手法による種同定

【目的】哺乳類から検出した2種類の寄生蠕虫の正確な種同定を行うことを目的とした。 【対象と方法】シカの大腸内から検出した線虫およびヒトから排出された条虫の表面構造を走査型電子顕微鏡 (SEM) により観察した。さらに，線虫については核5.8S-ITS2-28S リボソーマルRNA (rRNA) 遺伝子の，条虫についてはミトコンドリア16S rRNA遺伝子の部分塩基配列を決定し，その系統解析を行った。両者の結果を比較し，寄生虫種について考察した。 【結果】線虫は，ヤギやヒツジの寄生蠕虫であるOesophagostomum asperum，条虫は，クジラ複殖門条虫 (Diplogonoporus balaenopterae) とそれぞれ同定した。 【結論】SEMによる寄生虫体の表面構造の観察，塩基配列とその系統解析により，形態・遺伝子の双方向から寄生虫種の高精度な鑑別が可能であることを示した。journal articl

Elucidation of the Mechanism of Steroid-Related Osteonecrosis of the Femoral Head and Prevention of Its Occurrence

Idiopathic osteonecrosis of the femoral head leads to hip pain, gait disturbances, and rapid destruction of the hip joint. This disease is triggered by steroids, alcohol, and narrowly defined idiopathic conditions. Among these, steroid-related osteonecrosis, is considered a serious problem because of the effectiveness of steroids in various diseases and its widespread use in clinical practice. Although various studies have been conducted on the pathogenesis and prevention of this disease, no effective methods have been established. Therefore, the disease has been classified as intractable by the Ministry of Health, Labour, and Welfare. Although lipid metabolism disorders and abnormal coagulation/fibrinolysis systems have been proposed as mechanisms of pathogenesis, we focused on oxidative stress in our study. In addition, the possibility of inhibiting the occurrence of osteonecrosis by statins, drugs that improve lipid metabolism, and antioxidants has been reported in animal models as a method of preventing this disease. This review describes the characteristics of this disease, including its clinical features, and discuss its mechanisms and preventive measures, focusing on the oxidative stress theory, based on our research findings.journal articl

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Examination of Mandibular Morphology in Female Patients with Jaw Deformity Using Homologous Modeling Technology

Purpose: Following the shift toward more active treatment of jaw deformity, numerous institutions have reported trends in treatment techniques and the characteristics of jawbone morphology. However, few studies of patients undergoing treatment for jaw deformity have focused on mandibular morphology, which is an important factor in determining the surgical technique used. The aim of this study was to evaluate the efficacy of the homologous modeling technique for assessing the characteristics of mandibular bone morphology in patients with jaw deformity. Materials and Methods: Admitted to the study were 62 female patients (34 jaw deformity patients, 28 patients who required extraction of wisdom teeth) who underwent computed tomography imaging of the mandible at our department between April 2019 and July 2023. Homologous modeling of the mandible was performed using reference planes and anatomical landmarks, in addition to principal component analysis (PCA). The results of PCA between the jaw deformity group and the tooth extraction group were compared using Mann-Whitney U test. Results: PCA revealed positive associations among smaller mandibular angle, increased chin protrusion, and smaller angle of the mandibular ramus relative to the occlusal plane (principal component [PC] 1 and 2). Additionally, as the chin moved to the right, the angle of the mandibular ramus relative to the occlusal plane differed between the left and right sides (PC1). Conclusions: The homologous modeling technique is a useful method for evaluating the mandibular morphology of patients with jaw deformities.journal articl

Exploring AI’s Role in English Education for Medical Students

This study explores the role of generative AI tools in English education for first- and second-year medical students at Kanazawa Medical University. It investigates the students’ perceptions, usage habits, trust levels, and challenges associated with AI tools such as ChatGPT. The survey results reveal cautious optimism among the students; they acknowledge the potential of AI tools for writing and grammar-checking tasks but limit their use to conventional functions. The findings suggest the need for structured guidance to fully leverage the benefits of AI, emphasizing its role in fostering critical thinking and language proficiency. Additionally, the study discusses its limitations and suggests future research directions, including how students can better utilize AI for language learning.journal articl

Modified Reversed Blalock-Park Technique Utilizing the Aberrant Right Subclavian Artery for the Management of Mild Aortic Coarctation

The Blalock-Park procedure has historically been performed for coarctation of aorta and interruption of the aortic arch. We report a case of left bronchial stenosis following palliative surgery for unbalanced complete atrioventricular septal defect. The patient had tracheomalacia, mild aortic coarctation, and an aberrant right subclavian artery. Upon further examination, the left bronchial stenosis was identified as compression of the left bronchus by the contiguous descending aorta from an undivided ductus arteriosus and the aberrant right subclavian artery, as well as cardiac enlargement due to the palliative surgery. Aortopexy via left thoracotomy was performed. Intraoperatively, severe narrowing of the aortic isthmus was observed, leading to a reversed modified Blalock-Park procedure instead of dividing the aberrant right subclavian artery. This decision was based on concerns about potential future stenosis exacerbation, limiting perioperative medication management, and reoperation risks.journal articl

Establishment of Preclinical Trial of Lentiviral Gene Transfer to Prevent Bloom Syndrome-Related Hematological Malignancy

Bloom syndrome is a rare hereditary DNA repair disorder associated with a high risk of cancer. Patients with Bloom syndrome have a markedly increased risk of developing various cancers, particularly hematological malignancies, making cancer the leading cause of death in these individuals. Therefore, we hypothesized that the prevention of cancer could be a key point for these patients. This review focuses on designing a preclinical study exploring the potential of gene therapy to address this significant clinical challenge. Three issues were established for this preclinical study, and research is ongoing to solve these issues. The first was the development of an envelope-modified lentivirus designed to treat DNA repair disorders. This lentivirus has been engineered to effectively deliver therapeutic genes to cells affected by Bloom syndrome, and cytokine stimulation induces apoptosis in hematopoietic stem cells (HSCs). Second, we demonstrated that lentivirus-mediated gene transfer corrects the expression and function of BLM gene in bone marrow cells derived from a Bloom syndrome mouse model. These experiments indicated that the therapeutic gene delivered by the lentivirus can correct cellular defects associated with Bloom syndrome, thereby restoring normal cell function. Finally, we investigated the ability of gene therapy to prevent the development of radiation-induced tumors in BLM mice. By detailing the development and testing of this innovative gene therapy, this review demonstrated the potential of such treatments to transform the clinical management of DNA repair disorders, which could be translated into improved survival and quality of life in patients with Bloom syndrome.journal articl

Risk factors for photic phenomena in two different multifocal diffractive intraocular lenses

金沢医科大学博士（医学）2024thesi

Injury of Genome-Edited Mouse Embryos by Electroporation

Background: CRISPR-Cas9-based mouse gene modification, with its simplicity and higher recombination rate compared to embryonic stem cell methods, often involves electroporation into fertilized eggs; however, concerns about its impact on embryonic development. Methods: We conducted embryo culture experiments to assess the developmental impact of electroporation. To determine whether electroporated genome-edited embryos could actually implant in the uterus and become pups, embryo transfer experiments through the oviduct was also conducted. Viability and knock-in efficiency in resulting offspring were analyzed. Results and Conclusion: Electroporated embryos exhibited a significantly lower development rate (median 48.33%, interquartile range 38.03–59.66%) compared to non-electroporated embryos (median 85.00%, interquartile range 69.44–97.50%) at 96 hours post-electroporation. This decrease was consistent in electroporated embryos without the CRISPR-Cas9 complex (median 53.33%, interquartile range 33.44–69.08%, at 96 hours post-electroporation). Despite reduced viability, knock-in efficiency remained high at 62.82%. It is possible to achieve high recombination rates by combining electroporation and genome editing, but increasing the number of embryos to be transferred is required. These findings will be helpful in applications such as gene therapy and livestock genome editing.journal articl