Shiga University of Medical Science Repository BI WAKO / 滋賀医科大学機関リポジトリ
Not a member yet
4781 research outputs found
Sort by
Null mutation of exocyst complex component 3-like does not affect vascular development in mice
Get PDF滋賀医科大学博士（医学）Exp Anim. 2024 Feb 14;73(1):93-100.令和5年度thesi
Establishment of a novel mouse model of renal artery coiling-based chronic hypoperfusion-related kidney injury
Get PDF滋賀医科大学博士（医学）Renal artery stenosis-induced chronic renal ischemia is an important cause of renal dysfunction, especially in older adults, and its incidence is currently increasing. To elucidate the mechanisms underlying chronic renal hypoperfusion-induced kidney damage, we developed a novel mouse model of renal artery coiling-based chronic hypoperfusion-related kidney injury. This model exhibits decreased renal blood flow and function, atrophy, and parenchymal injury in the coiled kidney, along with compensatory hypertrophy in the non-coiled kidney, without chronic hypertension. The availability of this mouse model, which can develop renal ischemia without genetic modification, will enhance kidney disease research by serving as a new tool to investigate the effects of acquired factors (e.g., obesity and aging) and genetic factors on renal artery stenosis-related renal parenchymal damage.令和5年度doctoral thesi
Association with the nonparoxysmal atrial fibrillation duration and outcome of ExTRa Mapping-guided rotor ablation
Get PDF滋賀医科大学博士（医学）Background:
Additional ablation strategies after pulmonary vein isolation (PVI) for patients with nonparoxysmal atrial fibrillation (non-PAF) lasting ≥2 years have not been fully effective. This is presumably because of insufficient identification of non-PAF maintenance mechanisms. In this study, we employed a novel online and real-time phase mapping system, ExTRa Mapping, to identify and modulate rotors as one of the non-PAF maintenance mechanisms in patients with non-PAF sustained after PVI. We investigated the relationship between outcomes of ExTRa Mapping-guided rotor ablation (ExTRa-ABL) and non-PAF duration prior to this procedure.
Methods:
This study consisted of 73 non-PAF patients (63 ± 8 years, non-PAF duration 31 ± 37 months) who underwent the first ExTRa-ABL in patients with non-PAF sustained after completion of PVI.
Results:
Freedom from non-PAF/atrial tachycardia (AT) recurrence at 12 months after ExTRa-ABL was achieved in 50 (69%) of patients. The non-PAF duration prior to ExTRa-ABL was significantly longer in patients with non-PAF/AT recurrence after ExTRa-ABL compared with those without (56 ± 50 vs. 19 ± 22 months, p = .001). In patients with non-PAF duration of ≤60 months prior to ExTRa-ABL, compared with >60 months, non-PAF/AT-free rate was significantly higher (68.9% vs. 23.1%, p < .001), during the follow-up of 36 ± 18 months.
Conclusions:
A non-PAF duration of ≤60 months prior to ExTRa-ABL was associated with a better outcome. The effect of ExTRa-ABL was considered to be limited in patients with >60 months of non-PAF duration.令和5年度doctoral thesi
Nicotinic acetylcholine receptor activation induces BACE1 transcription via the phosphorylation and stabilization of nuclear SP1
Get PDFEpidemiological studies have shown that cigarette smoking increases the risk of Alzheimer disease. However, inconsistent results have been reported regarding the effects of smoking or nicotine on brain amyloid β (Aβ) deposition. In this study, we found that stimulation of the nicotinic acetylcholine receptor (nAChR) increased Aβ production in mouse brains and cultured neuronal cells. nAChR activation triggered the MEK/ERK pathway, which then phosphorylated and stabilized nuclear SP1. Upregulated SP1 acted on two recognition motifs in the BACE1 gene to induce its transcription, resulting in enhanced Aβ production. Mouse brain microdialysis revealed that nAChR agonists increased Aβ levels in the interstitial fluid of the cerebral cortex but caused no delay of Aβ clearance. In vitro assays indicated that nicotine inhibited Aβ aggregation. We also found that nicotine modified the immunoreactivity of anti-Aβ antibodies, possibly through competitive inhibition and Aβ conformation changes. Using anti-Aβ antibody that was carefully selected to avoid these effects, we found that chronic nicotine treatment in Aβ precursor protein knockin mice increased the Aβ content but did not visibly change the aggregated Aβ deposition in the brain. Thus, nicotine influences brain Aβ deposition in the opposite direction, thereby increasing Aβ production and inhibiting Aβ aggregation.journal articl
An Efficient Algorithm for Astrochemical Systems Using Stoichiometry Matrices
Get PDFAstrochemical simulations are a powerful tool for revealing chemical evolution in the interstellar medium. Astrochemical calculations require efficient processing of large matrices for the chemical networks. The large chemical reaction networks often present bottlenecks for computation because of time derivatives of chemical abundances. We propose an efficient algorithm using a stoichiometry matrix approach in which this time-consuming part is expressed as a loop, unlike the algorithm used in previous studies. Since stoichiometry matrices are sparse in general, the performances of simulations with our algorithm depend on which sparse-matrix storage format is used. We conducted a performance comparison experiment using the common storage formats, including the coordinate format, the compressed column storage format, the compressed row storage (CRS) format, and the sliced ELLPACK format. Experimental results showed that the simulations with the CRS format are the most suitable for astrochemical simulations and about a factor of 2 faster than those with the algorithm used in previous studies. In addition, our algorithm significantly reduces not only the computation time but also the compilation time. We also explore the beneficial effects of parallelization and sparse-matrix reordering in these algorithms.journal articl
A novel therapeutic target for kidney diseases: Lessons learned from starvation response
Get PDFThe prevalence of chronic kidney disease (CKD) is increasing worldwide, making the disease an urgent clinical challenge. Caloric restriction has various anti-aging and organ-protective effects, and unraveling its molecular mechanisms may provide insight into the pathophysiology of CKD. In response to changes in nutritional status, intracellular nutrient signaling pathways show adaptive changes. When nutrients are abundant, signals such as mechanistic target of rapamycin complex 1 (mTORC1) are activated, driving cell proliferation and other processes. Conversely, others, such as sirtuins and AMP-activated protein kinase, are activated during energy scarcity, in an attempt to compensate. Autophagy, a cellular self-maintenance mechanism that is regulated by such signals, has also been reported to contribute to the progression of various kidney diseases. Furthermore, in recent years, ketone bodies, which have long been considered to be detrimental, have been reported to play a role as starvation signals, and thereby to have renoprotective effects, via the inhibition of mTORC1. Therefore, in this review, we discuss the role of mTORC1, which is one of the most extensively studied nutrient-related signals associated with kidney diseases, autophagy, and ketone body metabolism; and kidney energy metabolism as a novel therapeutic target for CKD.journal articl
Allogeneic Hematopoietic Cell Transplantation Ameliorated Asymptomatic Granulomatous and Lymphocytic Interstitial Lung Disease in a Patient With XIAP Deficiency
No full textX-linked inhibitor of apoptosis protein (XIAP) deficiency is an inborn error of immunity (IEI). Allogeneic hematopoietic cell transplantation (HCT) is currently the only curative therapy available for XIAP deficiency. Granulomatous and lymphocytic interstitial lung disease (GLILD) is a common immune-related lung complication of IEIs. We present a 6-year-old boy with XIAP deficiency and GLILD. Computed tomography showed lung nodes but no symptoms. Before HCT, GLILD was not managed with immunosuppressive therapy, because he was asymptomatic. The HCT procedure was subsequently performed. The post-HCT course was uneventful; follow-up computed tomography on day 46 showed nodules had disappeared. HCT could potentially ameliorate GLILD like other inflammatory processes associated with the underlying IEIs.journal articl