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Neuronal-Hematopoietic Cell Fusion in Diabetic Neuropathy
application/pdfDiabetic neuropathy is a major complication of diabetes mellitus that occurs during the early stages of the disease. Many pathogenic mechanisms are related and induced by hyperglycemia. However, even if these factors improve, diabetic neuropathy cannot go into remission and progresses slowly. Furthermore, diabetic neuropathy often progresses even with proper glycemic control. Recently, bone marrow-derived cells (BMDCs) were reported to be involved in the pathogenesis of diabetic neuropathy. BMDCs expressing proinsulin and TNFα migrate to the dorsal root ganglion and fuse with neurons, and this neuronal-hematopoietic cell fusion induces neuronal dysfunction and apoptosis. The CD106-positive lineage-sca1+c-kit+ (LSK) stem cell fraction in the bone marrow is strongly involved in cell fusion with neurons, leading to diabetic neuropathy. Surprisingly, when CD106-positive LSK stem cells obtained from diabetic mice were transplanted into nondiabetic mice, they fused with dorsal root ganglion neurons and induced neuropathy in non-hyperglycemic normal mice. The transplanted CD106-positive LSK fraction inherited the trait even after transplantation; this "progeny effect" may explain the irreversibility of diabetic neuropathy and is a significant finding for determining the target of radical treatments and provides new directions for developing therapeutic methods for diabetic neuropathy.Journal Articlejournal articl
Bivalent monomer bearing styryl and five-membered cyclic dithiocarbonate moieties for orthogonal radical and cationic ring-opening polymerizations
application/pdfWe synthesized a novel bivalent monomer 1 bearing 4-vinylbenzyl group and five-membered cyclic dithiocarbonate. This monomer 1 was polymerized orthogonally by free radical polymerization to afford polystyrene 1a bearing a five-membered cyclic dithiocarbonate moiety in the side chain. On the other hand, cationic ring-opening polymerization of five-membered cyclic dithiocarbonate in the monomer 1 successfully proceeded, resulting in a narrow molecular weight distribution of polydithiocarbonate 1b bearing a 4-vinylbenzyl group in the side chain. Furthermore, post-polymerizations of 1a and 1b maintaining the polymerizable functionality were carried out respectively by suitable polymerization methods. The five-membered cyclic dithiocarbonate of 1a underwent cationic ring-opening polymerization with a high molar ratio of methyl trifluoromethanesulfonate at a high temperature compared to the case of monomer 1, whereas radical polymerization of the 4-vinylbenzyl group of 1b successfully proceeded under the almost same conditions as the case of monomer 1. These post-polymerizations achieved the synthesis of corresponding networked polymers 2a and 2b.Journal Articlejournal articl
Urine volume to hydration volume ratio is associated with pharmacokinetics of high-dose methotrexate in patients with primary central nervous system lymphoma
滋賀医科大学博士(医学)application/pdfThesis or DissertationPharmacology research & perspectives. 2021 Dec;9(6):e00883.令和4年度thesi
Availability of death review of children using death certificates and forensic autopsy results
滋賀医科大学博士(医学)application/pdfThesis or DissertationLegal medicine (Tokyo, Japan). 2023 Feb;60:102156.令和4年度thesi
Education for appropriate seatbelt use required for early-phase pregnant women drivers
滋賀医科大学博士(医学)application/pdfThesis or DissertationScientific Reports. 2020 Oct 19;10(1):17609.令和4年度thesi
添い寝・添え乳に起因した乳児の窒息死に関する実態と安全な授乳環境に関する考案
滋賀医科大学修士(看護学)application/pdfThesis or Dissertation令和4年度thesi
Relationship of leisure-time and household physical activity level and type with cardiovascular disease: secondary analysis of the Takashima Study data
滋賀医科大学博士(医学)application/pdfBackground:
High levels of participation in leisure-time and household physical activity lower the risk of cardiovascular disease (CVD), although it is unclear whether the number of activity types is related to new-onset CVD. We aimed to evaluate the effect of the amount of leisure-time physical activity and the number of types of leisure-time physical activities on the risk of CVD incidence.Methods:
From 2002 to 2003, 3,741 participants without any history of CVD participated in the Takashima Study. Data on the amount of leisure-time and household physical activity and the types of leisure-time and household physical activity were obtained from a self-administered questionnaire. Hazard ratios for CVD (acute myocardial infarction and stroke) incidence (follow-up data from 2002 to 2013), according to the participation level and number of activity types, were calculated using Cox proportional hazards models.Results:
The mean age of the subjects was 58.7 ± 13.1 years. During the mean follow-up period of 8.0 ± 1.1 years, 92 participants developed CVD. An inverse dose-response relationship was noted between the amount of leisure-time and household physical activity and CVD events. After adjusting for baseline characteristics, lifestyle-related diseases, and the amount of physical activity other than leisure-time and household, the risk of CVD onset was compared by dividing the participants into two groups by the level of participation; the highest activity group had an adjusted hazard ratio (95% confidence interval) of 0.40 (0.20-0.82) compared to the lowest activity group. Compared to participants who engaged in 0-1 type of activity, participants who engaged in two or more types of activities had a multivariable-adjusted hazard ratio (95% confidence interval) of 0.31 (0.12-0.79).Conclusion:
Increasing the amount of leisure-time and household physical activity and promoting engagement in two or more types of such activities may reduce the rate of CVD incidence in the Japanese general population.Thesis or Dissertation令和4年度doctoral thesi
Is central repair with coronary artery bypass grafting enough for multi-organ malperfusion in acute type A aortic dissection with coronary malperfusion?
滋賀医科大学博士(医学)Asian journal of surgery. 2023 Dec;46(12):5449-5453.令和5年度thesi
Diagnostic accuracy of cerebrospinal fluid liquid biopsy and MRI for leptomeningeal metastases in solid cancers : A systematic review and meta-analysis
Background:
Cerebrospinal fluid (CSF) cytology remains the gold standard approach for diagnosing of leptomeningeal metastases (LM), but has clinical problems due to its low sensitivity. This systemic review and meta-analysis evaluated the diagnostic accuracy of the novel CSF biomarkers of liquid biopsy and magnetic resonance imaging (MRI) for detecting LM in patients with solid cancers.
Methods:
A systematic search of electronic databases was conducted to identify all published diagnostic accuracy studies on CSF liquid biopsies and MRI since January 2000 with registration for PROSPERO (#CRD42022301988). Articles were selected based on pre-defined inclusion and exclusion criteria following the PRISMA 2020 statement.
Results:
The search yielded 3790 citations, and 10 studies with 668 patients were included in the final analysis. The pooled prevalence of LM was 50.9% (340/668). The respective sensitivity and specificity for index tests were as follows: circulating tumor cells (CTC), 87.0% (95% confidence interval [CI] 77.9-92.6%) and 93.8% (86.9-97.2%); cell-free tumor DNA, 97.9% (19.3-100%) and 89.0% (25.3-99.5%); MRI 59.4% (60.7-76.9%) and 97.6% (77.3-99.8%); cytology, 71.9% (54.7-82.9%) and 100%. The diagnostic odds ratio was 100.6 (29.38-344.09) for CTC and 93.3 (88.42-1034.05) for MRI.
Conclusion:
Novel CSF liquid biopsies and MRI may offer improved diagnostic accuracy for LM from solid cancers; however, further research is required to specify the threshold values and to construct standards for individual primary cancers.journal articl
O-linked N-acetylglucosamine modification is essential for physiological adipose expansion induced by high-fat feeding
Adipose tissues accumulate excess energy as fat and heavily influence metabolic homeostasis. O-linked N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation), which involves the addition of N-acetylglucosamine to proteins by O-GlcNAc transferase (Ogt), modulates multiple cellular processes. However, little is known about the role of O-GlcNAcylation in adipose tissues during body weight gain due to overnutrition. Here, we report on O-GlcNAcylation in mice with high-fat diet (HFD)-induced obesity. Mice with knockout of Ogt in adipose tissue achieved using adiponectin promoter-driven Cre recombinase (Ogt-FKO) gained less body weight than control mice under HFD. Surprisingly, Ogt-FKO mice exhibited glucose intolerance and insulin resistance, despite their reduced body weight gain, as well as decreased expression of de novo lipogenesis genes and increased expression of inflammatory genes, resulting in fibrosis at 24 weeks of age. Primary cultured adipocytes derived from Ogt-FKO mice showed decreased lipid accumulation. Both primary cultured adipocytes and 3T3-L1 adipocytes treated with OGT inhibitor showed increased secretion of free fatty acids. Medium derived from these adipocytes stimulated inflammatory genes in RAW 264.7 macrophages, suggesting that cell-to-cell communication via free fatty acids might be a cause of adipose inflammation in Ogt-FKO mice. In conclusion, O-GlcNAcylation is important for healthy adipose expansion in mice. Glucose flux into adipose tissues may be a signal to store excess energy as fat.NEW & NOTEWORTHY We evaluated the role of O-GlcNAcylation in adipose tissue in diet-induced obesity using adipose tissue-specific Ogt knockout mice. We found that O-GlcNAcylation in adipose tissue is essential for healthy fat expansion and that Ogt-FKO mice exhibit severe fibrosis upon long-term overnutrition. O-GlcNAcylation in adipose tissue may regulate de novo lipogenesis and free fatty acid efflux to the degree of overnutrition. We believe that these results provide new insights into adipose tissue physiology and obesity research.journal articl