Gifu University of Medical Science

About: Gifu University of Medical Science is a education organization based out in Gifu City, Japan. It is known for research contribution in the topics: Imaging phantom & Motion sickness. The organization has 89 authors who have published 202 publications receiving 1350 citations.

In vitro metabolic profiles of adamantyl positional isomers of synthetic cannabinoids

Abstract: Illegal use of synthetic cannabinoids (SCs) is a serious problem worldwide. Legal regulation of SCs requires fundamental analytical studies regarding the differentiation of potential structural isomers. Accumulation of SC metabolic profiles is also essential for forensic investigation because SCs are immediately metabolized after intake. Thus, we investigated the in vitro metabolism of N-adamantyl-1-(tetrahydropyran-4-ylmethyl)-1H-indazole-3-carboxamide isomers (ATHs) using human liver microsomes (HLMs). Moreover, we validated the applicability of the isomeric differentiation by investigation of N-adamantyl-1-(4-fluorobenzyl)-1H-indazole-3-carboxamide isomers (AFUs). Metabolites were collected at designated time points during the incubation period with HLMs for up to 180 min. The structures of the metabolites were annotated on the basis of mass spectroscopic evidence obtained by liquid chromatography–ion trap–time of flight mass spectrometry. The secondary stage mass (MS2) spectra obtained from the protonated molecules revealed a clear difference in both ATHs and their major metabolites because of the stability of the adamantyl (AD) cation. In HLMs, ATHs were quickly metabolized, and hydroxylation of the AD ring was deduced as the major metabolic pathway. The major metabolites of ATH 1 and ATH 2 after 180 min showed dihydroxylation and monohydroxylation of the AD ring. The AFUs showed analytical and metabolic profiles similar to those of the ATHs described above. We characterized the metabolism of ATHs for the first time and discriminated between the two isomers by mass spectrometric analysis of either the parent compounds or their major metabolites. Our investigation of AFUs also demonstrated a useful method for distinguishing between AD isomers.

Mathematical Analysis of Skeletal Muscle Electromyogram and the Aging

Abstract: 1. はじめに 現存する筋電図検査法には幾つかの種類が ある.最も頻用されるものに,針筋電図法 (needle electro myography: nEMG)と表面筋電 図法(surface electro myography: sEMG)がある. これらの筋電図波形から生理学的な解釈をす る,即ち,異常を検出する場合,現状では, nEMG や sEMG の波形や sEMG の積分波形を, 験者が視覚的に捉え,彼等の主観により判断 が下されている. (a) nEMGでは,その障害が神経原性のものか 筋原性のものか,或いは両者である場合,急 性或いは亜急性のものか,慢性のものかにつ いて判断する重要な材料になっている.しか し,このプローブには針電極が用いられてい る.針電極は経皮的に筋組織内に刺入される ものである. (b) sEMGにおいては,不随意運動の診断とし て振戦運動のタイプ分け,ジストニアやスパ ズムの診断或いは両者の鑑別診断,不随意収 縮筋の部位特定など,その応用範囲は多岐に わたっている.sEMGの積分波形は,筋収縮 の相対的度合いの判断材料にされ,筋肉トレ ーニングの状態を評価する指標として使われ るなどしている. (c) sEMGは神経伝導検査の検出電位(誘発筋電 図)としても用いられている.誘発筋電図検査 においては,経皮的に末梢神経を電気刺激す る. (b)を除く何れの検査法も,侵襲性があり, 強い痛みを伴うものである.また,EMG全般 を通じて,上述のように験者の視覚による主 観的な判断に依存しており,筋の異常もしく はその回復の度合いを客観的に定量化する数 理アルゴリズムは確立していない.そこで, 筆者らは会陰筋群を例として,排尿障害に対 するバイオフィードバックトレーニング時に おけるsEMGの積分波形について評価を行う ための計量指標を考案し,その効果を検討し ている. 一方,歩行における股関節屈曲動作を行う ための筋肉(股関節屈筋群)が加齢に伴い急激 に減少することが最近注目されている.股関 節屈筋群には大腿直筋や腹筋などが含まれ, これらが高齢者の転倒にも関係していること が指摘されている.本研究では,大腿直筋に 対して上述の計量指標を応用して,利き足の バイオフィードバックトレーニング時におけ るsEMGの積分波形について評価を行い,その 経年変化を診ることを目的とした.

Novel ACTN1 variants in cases of thrombocytopenia.

Abstract: The ACTN1 gene has been implicated in inherited macrothrombocytopenia. To decipher the spectrum of variants and phenotype of ACTN1-related thrombocytopenia, we sequenced the ACTN1 gene in 272 cases of unexplained chronic or familial thrombocytopenia. We identified 15 rare, monoallelic, nonsynonymous and likely pathogenic ACTN1 variants in 20 index cases from 20 unrelated families. Thirty-one family members exhibited thrombocytopenia. Targeted sequencing was carried out on 12 affected relatives, which confirmed presence of the variant. Twenty-eight of 32 cases with monoallelic ACTN1 variants had mild to no bleeding complications. Eleven cases harbored 11 different unreported ACTN1 variants that were monoallelic and likely pathogenic. Nine variants were located in the α-actinin-1 (ACTN1) rod domain and were predicted to hinder dimer formation. These variants displayed a smaller increase in platelet size compared with variants located outside the rod domain. In vitro expression of the new ACTN1 variants induced actin network disorganization and led to increased thickness of actin fibers. These findings expand the repertoire of ACTN1 variants associated with thrombocytopenia and highlight the high frequency of ACTN1-related thrombocytopenia cases. The rod domain, like other ACTN1 functional domains, may be mutated resulting in actin disorganization in vitro and thrombocytopenia with normal platelet size in most cases.