夏目漱石 : 眼は識る東西の字

学位の種別: 論文博士審査委員会委員 : (主査)東京大学教授 菅原 克也, 東京大学教授 キャンベル ロバート, 東京大学教授 エリス 俊子, 東京大学准教授 佐藤 光, 東京大学名誉教授 平川 祐弘University of Tokyo(東京大学

Safety comparisons among monoamine oxidase inhibitors against Parkinson’s disease using FDA adverse event reporting system

Monoamine oxidase B (MAO-B) inhibitors are used to control Parkinson’s disease (PD). Selegiline, rasagiline, and safinamide are widely used as MAO-B inhibitors worldwide. Although these drugs inhibit MAO-B, there are pharmacological and chemical differences, such as the inhibitory activity, the non-dopaminergic properties in safinamide, and the amphetamine-like structure in selegiline. MAO-B inhibitors may differ in adverse events (AEs). However, differences in actual practical clinics are not fully investigated. A retrospective study was conducted using FAERS, the largest database of spontaneous adverse events. AE signals for MAO-B inhibitors, including selegiline, rasagiline, and safinamide, were detected using the reporting odds ratio method and compared. Hypocomplementemia, hepatic cyst, hepatic function abnormal, liver disorder and cholangitis were detected for selegiline as drug-specific signals. The amphetamine effect was not confirmed for any of the three MAO-B inhibitors. The tyramine reaction was detected as an AE signal only for rasagiline. Moreover, the REM sleep behavior disorder was not detected as an AE signal for safinamide, suggesting that non-dopaminergic effects might be beneficial. Considering the differences in AEs for MAO-B inhibitors will assist with the appropriate PD medication.Asano H., Tian Y.S., Hatabu A., et al. Safety comparisons among monoamine oxidase inhibitors against Parkinson’s disease using FDA adverse event reporting system. Scientific Reports 13, 19272 (2023); https://doi.org/10.1038/s41598-023-44142-2

Purification and Characterization of Chloroplast F_1-ATPase in Asetabularia acetabulum

FITC, fluorescein isothiocyanate ; DCCD, N, N\u27-dicyclohexylcarbodiimide ; Pipes, 1,4-piperazinediethanesulfonic acid ; Tris, tris (hydroxymethyl) aminomethane ; FPLC, fast protein liquid chromatography ; PMSF, phenylmethanesulfonyl fluoride ; DTT, dithiothreitol ; NEM, N-ethylmaleimide ; DES, diethylstilbestrol ; NBD-Cl, 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole ; PCR, polymerase chain reaction ; Rubisco, ribulose-1,5-bisphosphate carboxylase/oxygenas

The polymorphism in the caudal-related homeodomain protein Cdx-2 binding element in the human vitamin D receptor gene

The major physiological activity of 1,25-hydroxyvitamin D3 (1,25(OH)2D3) is the regulation of calcium absorption in the small intestine, and the level of vitamin D receptor (VDR) is an important factor in this regulation. In a previous study, we demonstrated that the caudal-related homeodomain Cdx-2 played an important role in the intestine-specific transcription of the human VDR gene. In the present study, the polymorphism was identified in the core sequence 5'-ATAAAAACTTAT-3' in the Cdx-2 binding site in the VDR gene promoter. In 261 Japanese women with genotyped VDR polymorphisms, 48 were genotype Cdx-A (adenine at-3731 nt relative to the transcription start site of human VDR gene, 5'-A_TAAAAACTTAT'-3'), 82 were genotype Cdx-G (guanine at-3731 nt, 5'-G_TAAAAACTTAT-3'), 131 were genotype Cdx-A/G (heterozygote). The bone mineral density (BMD) in the lumbar spine (L2-4) with the Cdx-A homozygote was 12% lower than that with the Cdx-G homozygote (P<0.05). In electropholertic gel mobility shift assay, the oligonucleotide with Cdx-G allele markedly decreased the binding to Cdx-2 compared with that in the Cdx-A allele. The transcriptional activity of the VDR promoter with Cdx-G allele was decreased to 70% of the Cdx-A allele. In addition, in the herpes simplex virus thymidine kinase promoter, the Cdx-2 binding element with the G allele showed significantly lower transcriptional activity than that of the A allele. Thus, the polymorphism in the Cdx-2 binding site of the VDR gene (Cdx-polymorphism) would affect the expression of VDR in the small intestine. In addition, this polymorphism may modulate BMD in postmenopausal Japanese women

A Simple and Specific Colorimetric Determination of Cysteine with p-Dimethylaminocinnamaldehyde

Peer Reviewe

Comprehensive quantification and genome survey reveal the presence of novel phytohormone action modes in red seaweeds

Emerging work has suggested the existence of phytohormones in seaweeds, although chemical species, endogenous biosynthetic pathways, and signal transduction machineries remain poorly understood. We performed profiling of nine phytohormones with liquid chromatography-mass spectrometry and in silico genome-wide homology search to identify genes involved in biosynthesis and signal transduction of hormones in red algae. It was demonstrated that two Bangiophycean algae, Bangia fuscopurpurea and Pyropia yezoensis, possessed indoleacetic acid (IAA), N-6-(Delta(2)-isopentenyl) adenine (iP), abscisic acid (ABA), and salicylic acid, although trans-zeatin, dihydrozeatin, gibberellin A(1) and A(4), and jasmonate were not detected. Results of genome-wide survey demonstrated that Bangiophycean algae produce iP and ABA via pathways similar to those in terrestrial plants. However, these seaweeds lack homologues of already known factors participating in perception and signal transduction of IAA, iP, ABA and SA, indicating that the action modes of these phytohormones in red seaweeds differ from those elucidated in terrestrial plants. These findings shed lights on evolutional divergence of signal transduction pathways of phytohormones in plants