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
Single-Nucleotide Polymorphisms, c.415C > T (Arg139Cys) and c.416G > A (Arg139His), in the NUDT15 Gene Are Associated with Thiopurine-Induced Leukopenia.
Get PDFWhile nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) gene polymorphism Arg139Cys (rs116855232) is known to be a risk factor for thiopurine-induced severe leukopenia, association with the NUDT15 gene polymorphism Arg139His (rs147390019) has not yet been clarified. In addition, the accuracy of TaqMan PCR to assess these two polymorphisms has not been investigated. In this study, we evaluated TaqMan PCR for detection of the NUDT15 single-nucleotide polymorphisms (SNPs) and examined the clinical impact of Arg139His on thiopurine-induced leukopenia. First, we demonstrated that a TaqMan PCR assay successfully detected the Arg139His polymorphism of NUDT15 in clinical samples. Next, the NUDT15 gene polymorphisms (Arg139Cys and Arg139His) were separately analyzed by TaqMan Real-Time PCR in 189 patients from August 2018 to July 2019. The incidences of leukopenia within 2 years were 16.2, 57.9, and 100% for arginine (Arg)/Arg, Arg/cysteine (Cys), and Arg/histidine (His), respectively. The leukopenia was significantly increased in Arg/Cys and Arg/His compared with Arg/Arg. This retrospective clinical study indicated that, in addition to Arg139Cys, Arg139His may be clinically associated with a high risk of leukopenia. Pharmacogenomics will help in selecting drugs and determining the individualized dosage of thiopurine drugs.journal articl
Subtype prevalence and baseline visual acuity by age in Japanese patients with neovascular age-related macular degeneration
No full textPurpose:
To investigate age-specific prevalence of disease subtypes and baseline best-corrected visual acuity (BCVA) in Japanese patients with treatment-naïve neovascular age-related macular degeneration (nAMD).Methods:
We reviewed the records of patients with treatment-naïve nAMD who underwent initial treatment in 14 institutions in Japan sometime during the period from 2006 to 2015. In patients in whom both eyes were treated, only the eye treated first was included for analysis. The patients were stratified by age for the analysis.Results:
In total, 3096 eyes were included. The overall prevalence of subtypes was as follows: typical AMD, 52.6%; polypoidal choroidal vasculopathy (PCV), 42.8%; retinal angiomatous proliferation (RAP), 4.6%. The number of eyes in each age group was as follows: younger than 60 years, 199; 60s, 747; 70s, 1308; 80s, 784; 90 years or older, 58. The prevalence of typical AMD in each age group was 51.8%, 48.1%, 52.1%, 57.7%, and 55.2%, respectively. The prevalence of PCV was 46.7%, 49.1%, 44.7%, 34.4%, and 19.0%, respectively. The prevalence of RAP was 1.5%, 2.8%, 3.2%, 7.9%, and 25.9%, respectively. The prevalence of PCV decreased with age, whilst that of RAP increased. The prevalence of RAP was higher than that of PCV in patients aged 90 years or older. The mean baseline BCVA (logMAR) was 0.53. In each age group, the mean baseline BCVA was 0.35, 0.45, 0.54, 0.62, and 0.88, respectively. The mean logMAR BCVA at baseline significantly worsened with age (P < 0.001).Conclusion:
The prevalence of nAMD subtypes differed according to age in Japanese patients. The baseline BCVA worsened with age.Journal Articlejournal articl
Association of Respiratory Functional Indices and Smoking with Pleural Movement and Mean Lung Density Assessed Using Four-Dimensional Dynamic-Ventilation Computed Tomography in Smokers and Patients with COPD
Get PDFapplication/pdfPurpose:
To correlate the ratio of the non-dependent to dependent aspects of the maximal pleural movement vector (MPMVND/D) and gravity-oriented collapse ratio (GCRND/D), and the mean lung field density (MLD) obtained using four-dimensional (4D) dynamic-ventilation computed tomography (DVCT) with airflow limitation parameters and the Brinkman index.Materials and methods:
Forty-seven patients, including 22 patients with COPD, 13 non-COPD smokers, and 12 non-smokers, with no/slight pleural adhesion confirmed using a thoracoscope, underwent 4D-DVCT with 16 cm coverage. Coordinates for the lung field center, as well as ventral and dorsal pleural points, set on the central trans-axial levels in the median and para-median sagittal planes at end-inspiration, were automatically measured (13-17 frame images, 0.35 seconds/frame). MPMVND/D and GCRND/D were calculated based on MPMV and GCR values for all the included points and the lung field center. MLD was automatically measured in each of the time frames, and the maximal change ratio of MLD (MLDCR) was calculated. These measured values were compared among COPD patients, non-COPD smokers, and non-smokers, and were correlated with the Brinkman index, FEV1/FVC, FEV1 predicted, RV/TLC, and FEF25-75% using Spearman's rank coefficients.Results:
MPMVND/D was highest in non-smokers (0.819±0.464), followed by non-COPD smokers (0.405±0.131) and patients with COPD (-0.219±0.900). GCRND/D in non-smokers (1.003±1.384) was higher than that in patients with COPD (-0.164±1.199). MLDCR in non-COPD smokers (0.105±0.028) was higher than that in patients with COPD (0.078±0.027). MPMVND/D showed positive correlations with FEV1 predicted (r=0.397, p=0.006), FEV1/FVC (r=0.501, p<0.001), and FEF25-75% (r=0.368, p=0.012). GCRND/D also demonstrated positive correlations with FEV1 (r=0.397, p=0.006), FEV1/FVC (r=0.445, p=0.002), and FEF25-75% (r=0.371, p=0.011). MPMVND/D showed a negative correlation with the Brinkman index (r=-0.398, p=0.006).Conclusion:
We demonstrated that reduced MPMVND/D and GCRND/D were associated with respiratory functional indices, in addition to a negative association of MPMVND/D with the Brinkman index, which should be recognized when assessing local pleural adhesion on DVCT, especially for ventral pleural aspects.Journal Articlejournal articl
A case of severe acute hyponatremia after colonoscopy with polyethylene glycol plus ascorbic acid bowel preparation
No full textPrevious reports have shown that bowel preparation can, in extremely rare circumstances, induce severe acute hyponatremia. Polyethylene glycol plus ascorbic acid as a bowel preparation is considered relatively safe with a smaller amount of free water load and a more pleasant taste with additives.We present the case of an 86-year-old man who developed severe acute hyponatremia presenting with tremor and impaired consciousness after colonoscopy, which is life-threatening. The severe hyponatremia in our case was not caused by free water loads from drinking large amounts of water during bowel preparation or hypovolemia due to bowel preparation-induced nausea, vomiting, and diarrhea, but might have been due to non-osmotic stimuli of antidiuretic hormone (ADH) release (i.e., pre-existing nausea, stress, anxiety, pain, stress, or the colonoscopy itself). Our study indicates that it is important to choose safer bowel preparation solutions, to be aware of ingested water volumes, to assess volume status, and also remain aware of other coexisting risk factors for acute hyponatremia, such as medical history, medication, and ADH release, especially in elderly patients.Journal Articlejournal articl
Curcumin tautomerization in the mechanism of pentameric amyloid- β42 oligomers disassembly.
Get PDFapplication/pdfAlzheimer's disease is a neurologic disorder characterized by the accumulation of extracellular deposits of amyloid-β (Aβ) fibrils in the brain of patients. The key etiologic agent in Alzheimer's disease is not known; however oligomeric Aβ appears detrimental to neuronal functions and increases Aβ fibrils deposition. Previous research has shown that curcumin, a phenolic pigment of turmeric, has an effect on Aβ assemblies, although the mechanism remains unclear. In this study, we demonstrate that curcumin disassembles pentameric oligomers made from synthetic Aβ42 peptides (pentameric oAβ42), using atomic force microscopy imaging followed by Gaussian analysis. Since curcumin shows keto-enol structural isomerism (tautomerism), the effect of keto-enol tautomerism on its disassembly was investigated. We have found that curcumin derivatives capable of keto-enol tautomerization also disassemble pentameric oAβ42, while, a curcumin derivative incapable of tautomerization did not affect the integrity of pentameric oAβ42. These experimental findings indicate that keto-enol tautomerism plays an essential role in the disassembly. We propose a mechanism for oAβ42 disassembly by curcumin based on molecular dynamics calculations of the tautomerism. When curcumin and its derivatives bind to the hydrophobic regions of oAβ42, the keto-form changes predominantly to the enol-form; this transition is associated with structural (twisting, planarization and rigidification) and potential energy changes that give curcumin enough force to act as a torsion molecular-spring that eventually disassembles pentameric oAβ42. This proposed mechanism sheds new light on keto-enol tautomerism as a relevant chemical feature for designing such novel therapeutic drugs that target protein aggregation.Journal Articlejournal articl
Novel CLOCK and NR1D2 variants in 64 sighted Japanese individuals with non-24-hour sleep-wake rhythm disorder
Get PDFjournal articl
Effects of common genetic variants of human uridine diphosphate glucuronosyltransferase subfamilies on irinotecan glucuronidation
Get PDF滋賀医科大学博士（医学）application/pdfThesis or DissertationToxicology Mechanisms and Methods . 2023 Mar;33(3):197-205.令和4年度thesi
Correct Use of a Conventional Lap-and-Shoulder Seatbelt Is Safest for Pregnant Rear-Seat Passengers: Proposal for Additional Safety Measures
Get PDF滋賀医科大学博士（医学）application/pdfThesis or DissertationApplied Sciences. 2022, 12(17), 8776令和4年度thesi
Effect of internal limiting membrane peeling on postoperative visual acuity in macula-off rhegmatogenous retinal detachment
Get PDF滋賀医科大学博士（医学）application/pdfThesis or DissertationPLoS One. 2021 Aug 5;16(8):e0255827.令和4年度thesi
Vascular smooth muscle RhoA counteracts abdominal aortic aneurysm formation by modulating MAP4K4 activity.
Get PDF滋賀医科大学博士（医学）application/pdfThesis or DissertationCommunications Biology. 2022 Oct 7;5(1):1071.令和4年度thesi