Differential diagnosis of nonepileptic twilight state with convulsive manifestations after febrile seizures

Background Nonepileptic twilight state with convulsive manifestations (NETC) is a nonepileptic state following a febrile seizure (FS), which may be misdiagnosed as a prolonged seizure and result in overtreatment. We aimed to describe clinical manifestations of NETC and to determine characteristics that are helpful to distinguish NETC from other pathological conditions. Methods We conducted a retrospective chart review from January 2010 to December 2016 and selected the patients who presented with symptoms resembling status epilepticus with fever and a confirmed diagnosis using an electroencephalogram (EEG). We compared the NETC clinical features and venous blood gas analysis results with those of other conditions that mimic NETC. We also compared the characteristics of NETC with past reports. Results Our NETC patients presented with short durations of the preceding generalized convulsions followed by tonic posturing, closed eyes, no cyanosis, responsiveness to painful stimulation, and no accumulation of CO2 in the venous blood gas. Most of these characteristics were consistent with past reports. Prolonged FS or acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) showed several of these features, but all the characteristics were not consistent with our study. Conclusions Prolonged FS and AESD need to be differentiated from NETC, and close clinical observation makes it possible to partially distinguish NETC from the other conditions. EEG is recommended for patients with symptoms that are inconsistent with these features

Impact of Gba2 on neuronopathic Gaucher’s disease and α-synuclein accumulation in medaka (Oryzias latipes)

Homozygous mutations in the lysosomal glucocerebrosidase gene, GBA1, cause Gaucher's disease (GD), while heterozygous mutations in GBA1 are a strong risk factor for Parkinson's disease (PD), whose pathological hallmark is intraneuronal α-synuclein (asyn) aggregates. We previously reported that gba1 knockout (KO) medaka exhibited glucosylceramide accumulation and neuronopathic GD phenotypes, including short lifespan, the dopaminergic and noradrenergic neuronal cell loss, microglial activation, and swimming abnormality, with asyn accumulation in the brains. A recent study reported that deletion of GBA2, non-lysosomal glucocerebrosidase, in a non-neuronopathic GD mouse model rescued its phenotypes. In the present study, we generated gba2 KO medaka and examined the effect of Gba2 deletion on the phenotypes of gba1 KO medaka. The Gba2 deletion in gba1 KO medaka resulted in the exacerbation of glucosylceramide accumulation and no improvement in neuronopathic GD pathological changes, asyn accumulation, or swimming abnormalities. Meanwhile, though gba2 KO medaka did not show any apparent phenotypes, biochemical analysis revealed asyn accumulation in the brains. gba2 KO medaka showed a trend towards an increase in sphingolipids in the brains, which is one of the possible causes of asyn accumulation. In conclusion, this study demonstrated that the deletion of Gba2 does not rescue the pathological changes or behavioral abnormalities of gba1 KO medaka, and GBA2 represents a novel factor affecting asyn accumulation in the brains

Common Peak Approach Using Mass Spectrometry Data Sets for Predicting the Effects of Anticancer Drugs on Breast Cancer

We propose a method for biomarker discovery from mass spectrometry data, improving the common peak approach developed by Fushiki et al. (BMC Bioinformatics, 7:358, 2006). The common peak method is a simple way to select the sensible peaks that are shared with many subjects among all detected peaks by combining a standard spectrum alignment and kernel density estimates. The key idea of our proposed method is to apply the common peak approach to each class label separately. Hence, the proposed method gains more informative peaks for predicting class labels, while minor peaks associated with specific subjects are deleted correctly. We used a SELDI-TOF MS data set from laser microdissected cancer tissues for predicting the treatment effects of neoadjuvant therapy using an anticancer drug on breast cancer patients. The AdaBoost algorithm is adopted for pattern recognition, based on the set of candidate peaks selected by the proposed method. The analysis gives good performance in the sense of test errors for classifying the class labels for a given feature vector of selected peak values

Glucosylated cholesterol in mammalian cells and tissues: formation and degradation by multiple cellular β-glucosidases.

The membrane lipid glucosylceramide (GlcCer) is continuously formed and degraded. Cells express two GlcCer-degrading β-glucosidases, glucocerebrosidase (GBA) and GBA2, located in and outside the lysosome, respectively. Here we demonstrate that through transglucosylation both GBA and GBA2 are able to catalyze in vitro the transfer of glucosyl-moieties from GlcCer to cholesterol, and vice versa. Furthermore, the natural occurrence of 1-O-cholesteryl-β-D-glucopyranoside (GlcChol) in mouse tissues and human plasma is demonstrated using LC-MS/MS and (13)C6-labeled GlcChol as internal standard. In cells, the inhibition of GBA increases GlcChol, whereas inhibition of GBA2 decreases glucosylated sterol. Similarly, in GBA2-deficient mice, GlcChol is reduced. Depletion of GlcCer by inhibition of GlcCer synthase decreases GlcChol in cells and likewise in plasma of inhibitor-treated Gaucher disease patients. In tissues of mice with Niemann-Pick type C disease, a condition characterized by intralysosomal accumulation of cholesterol, marked elevations in GlcChol occur as well. When lysosomal accumulation of cholesterol is induced in cultured cells, GlcChol is formed via lysosomal GBA. This illustrates that reversible transglucosylation reactions are highly dependent on local availability of suitable acceptors. In conclusion, mammalian tissues contain GlcChol formed by transglucosylation through β-glucosidases using GlcCer as donor. Our findings reveal a novel metabolic function for GlcCer.This study was made possible by the ERC AdG CHEMBIOSPHIN. The authors declare no financial conflicts of interest relevant to this study

Recent Results from LHD Experiment with Emphasis on Relation to Theory from Experimentalist’s View

he Large Helical Device (LHD) has been extending an operational regime of net-current free plasmas towardsthe fusion relevant condition with taking advantage of a net current-free heliotron concept and employing a superconducting coil system. Heating capability has exceeded 10 MW and the central ion and electron temperatureshave reached 7 and 10 keV, respectively. The maximum value of β and pulse length have been extended to 3.2% and 150 s, respectively. Many encouraging physical findings have been obtained. Topics from recent experiments, which should be emphasized from the aspect of theoretical approaches, are reviewed. Those are (1) Prominent features in the inward shifted configuration, i.e., mitigation of an ideal interchange mode in the configuration with magnetic hill, and confinement improvement due to suppression of both anomalous and neoclassical transport, (2) Demonstration ofbifurcation of radial electric field and associated formation of an internal transport barrier, and (3) Dynamics of magnetic islands and clarification of the role of separatrix

A Congratulatory Address For Best Book Award To Emeritus Professor Yasuhiro Kobayashi

その他：学会賞祝

細胞の三次元様増殖を指標とした温熱療法の最適条件に関する研究

本研究の目的は、三次元様増殖に温熱刺激が効果的に働く最適量と最小量を示すことであった。C3H10T1/2マウス線維芽細胞とハイドロキシアパタイトを混合し、設定温度が40℃・41.5℃・43℃・44℃・45℃、処理時間は2分間・10分間・15分間・20分間・30分間・45分間・60分間・90分間・180分間・360分間の温熱刺激を与えて10週間培養することにより三次元様増殖形成に必要な最小と最適な温熱量を調べた。その結果、三次元様増殖形成に必要な最小の温熱量は43℃2分間、また最適な温熱量は43℃10分間であった。43℃2分間は非処理対照の1.7倍、43℃10分間では3.7倍と非常に高い形成率となり、それぞれ有意差がみられた(p<0.05)。また、40℃で90分間・180分間と41.5℃15分間および44℃10分間も対照群に比べ高い形成率であった。43℃10分間の温熱処理では1週間後に約80%がアポトーシスになっていた。ウエスタンブロット分析により43℃10分間の温熱処理によってp38 MAPK の活性化が明らかであった。これらの結果から、温熱刺激による三次元様増殖はp38 MAPK の経路を介していることが判明した。本研究結果は最適な温熱量を提示するものとして温熱療法の基礎となり、温熱療法の効果を細胞生物学的に示すための重要な知見になると考えられる