Publications by authors named "Shunsuke Kobayashi"

133 Publications

Evaluation of the effect of apixaban using a viscoelastic coagulation assay with Russell's viper venom reagent.

JA Clin Rep 2021 May 6;7(1):42. Epub 2021 May 6.

Department of Anesthesiology, The Jikei University School of Medicine, 3-25-8 Nishishinbashi, Minato-ku, Tokyo, 105-8461, Japan.

Background: Conventional coagulation tests, such as prothrombin time and activated partial thromboplastin time, are not sensitive to anticoagulation by apixaban. We evaluated the antithrombotic effect of apixaban using a Russell viper venom (RVV) test for a patient who underwent posterior spine fusion surgery.

Case Presentation: An 84-year-old man was scheduled for percutaneous posterior spine fusion. He continued apixaban until the night before surgery and resumed it on the first day after surgery. We performed an RVV test as point-of-care coagulation monitoring in combination with chromogenic anti-activated factor X (anti-Xa) activity, prothrombin time, and activated partial thromboplastin time. Clotting time with the RVV test was prolonged according to the anti-Xa activity of apixaban, which was in the therapeutic range during surgery.

Conclusions: An RVV test might be useful as a point-of-care assay for estimation of the anti-Xa level induced by apixaban during the perioperative period.
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http://dx.doi.org/10.1186/s40981-021-00445-9DOI Listing
May 2021

Acute retrobulbar optic neuritis with anti-myelin oligodendrocyte glycoprotein antibody-associated disease complicated with microscopic polyangiitis: A case report.

Medicine (Baltimore) 2021 Apr;100(15):e24889

Department of Rheumatology.

Rationale: Anti-myelin oligodendrocyte protein antibody-associated disease (MOGAD) is a new disease entity with various clinical phenotypes. MOGAD often present with recurrent optic neuritis (ON), and it can also develop as a compartment of neuromyelitis optica spectrum disorder (NMOSD). Moreover, multiple autoantibodies such as an anti-myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) had been reported in the serum of patients with NMOSD.

Patient Concerns: We report an 86-year-old woman with a 2-year history of microscopic polyangiitis (MPA). The patient had a rapid loss of vision in her left eye. No abnormal findings were observed on her left fundus, and she tested negative for MPO-ANCA upon admission. However, anti-MOG antibodies were observed in the patient's serum and cerebrospinal fluid.

Diagnosis: A diagnosis of MOGAD complicated with MPA was made.

Interventions: The patient received twice steroid pulse therapy and oral azathioprine as maintenance therapy.

Outcomes: Her vision rapidly recovered, and no subsequent relapse was observed during the 8-month observation period.

Conclusion: To the best of our knowledge, this is the first case of MOGAD complicated with MPA, and steroid pulse therapy and azathioprine therapy were effective for ON caused by MOGAD.
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http://dx.doi.org/10.1097/MD.0000000000024889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052052PMC
April 2021

Event-Related Potentials During Decision-Making in a Mixed-Strategy Game.

Front Neurosci 2021 19;15:552750. Epub 2021 Mar 19.

Department of Neurology, Teikyo University, Tokyo, Japan.

The decisions we make are sometimes influenced by interactions with other agents. Previous studies have suggested that the prefrontal cortex plays an important role in decision-making and that the dopamine system underlies processes of motivation, motor preparation, and reinforcement learning. However, the physiological mechanisms underlying how the prefrontal cortex and the dopaminergic system are involved in decision-making remain largely unclear. The present study aimed to determine how decision strategies influence event-related potentials (ERPs). We also tested the effect of levodopa, a dopamine precursor, on decision-making and ERPs in a randomized double-blind placebo-controlled investigation. The subjects performed a matching-pennies task against an opposing virtual computer player by choosing between right and left targets while their ERPs were recorded. According to the rules of the matching-pennies task, the subject won the trial when they chose the same side as the opponent, and lost otherwise. We set three different task rules: (1) with the alternation (ALT) rule, the computer opponent made alternating choices of right and left in sequential trials; (2) with the random (RAND) rule, the opponent randomly chose between right and left; and (3) with the GAME rule, the opponent analyzed the subject's past choices to predict the subject's next choice, and then chose the opposite side. A sustained medial ERP became more negative toward the time of the subject's target choice. A biphasic potential appeared when the opponent's choice was revealed after the subject's response. The ERPs around the subject's choice were greater in RAND and GAME than in ALT, and the negative peak was enhanced by levodopa. In addition to these medial ERPs, we observed lateral frontal ERPs tuned to the choice direction. The signals emerged around the choice period selectively in RAND and GAME when levodopa was administered. These results suggest that decision processes are modulated by the dopamine system when a complex and strategic decision is required, which may reflect decision updating with dopaminergic prediction error signals.
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http://dx.doi.org/10.3389/fnins.2021.552750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017162PMC
March 2021

Acute aortic dissection with highly compressed true lumen: unanticipated pitfall of point-of-care ultrasonography.

BMJ Case Rep 2021 Mar 2;14(3). Epub 2021 Mar 2.

Department of Emergency and Critical Care Medicine, Seirei Hamamatsu Hospital, Hamamatsu, Japan.

A 46-year-old man presented with sudden onset of chest pain. He was in cardiogenic shock at arrival. Based on the results of ECG and echocardiogram, he was diagnosed with ST-segment elevation myocardial infarction. Point-of-care ultrasonography (POCUS) did not reveal acute aortic dissection (AAD). During an emergency coronary angiography, aortic dissection was detected and computed tomographic angiography (CTA) revealed Stanford type A AAD with a highly compressed true lumen. Because of this form of aortic dissection, the enlarged false lumen could be potentially misidentified as a normal aorta in POCUS. Although POCUS is useful when AAD is suspected, we should not overestimate its findings and lower the threshold for CTA.
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http://dx.doi.org/10.1136/bcr-2020-239328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929881PMC
March 2021

7-Hydorxyindirubin is capable of specifically inhibiting anticancer drug-induced YB-1 nuclear translocation without showing cytotoxicity in HepG2 hepatocellular carcinoma cells.

Biochem Biophys Res Commun 2021 Mar 28;544:15-21. Epub 2021 Jan 28.

Laboratory of Biochemistry, School of Pharmacy, Nihon University, Narashinodai, Funabashi, Chiba, 274-8555, Japan. Electronic address:

Hepatocellular carcinoma (HCC) is one of the most common human malignant tumors. It is known that in the cells of many cancers, including HCC, nuclear translocation and accumulation of YB-1 often indicates a poor prognosis. This nuclear translocation is induced by genotoxic stress resulting from administration of anticancer agents. Accumulation of YB-1 in the nucleus induces the expression of many genes related to cancer aggressiveness. Therefore, compounds capable of inhibiting anticancer drug-induced YB-1 nuclear translocation without cytotoxicity will be a powerful tool for cancer chemotherapy. In the present study, we found that indirubin derivative, 7-hydroxyindirubin strongly inhibited the actinomycin D-induced nuclear translocation of YB-1 more efficiently without showing cytotoxicity in HepG2, a human HCC cells. The compound successfully suppressed the nuclear YB-1-mediated expression of genes such as MDR1, MVP, EGFR, and CXCR4, which are known to disturb cancer treatment. 7-Hydroxyindirubin also increased the susceptibility of drug-resistant HepG2 cells to ActD. It was also demonstrated that 7-hydroxyindirubin inhibits the nuclear translocation of YB-1 with or without phosphorylation at the Ser102 residue.
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http://dx.doi.org/10.1016/j.bbrc.2021.01.048DOI Listing
March 2021

Aquaporin-4-antibody-positive Neuromyelitis Optica Spectrum Disorder in a Patient with Charcot-Marie-Tooth Disease Type 1A.

Intern Med 2020 Dec 22. Epub 2020 Dec 22.

Department of Neurology, Teikyo University School of Medicine, Japan.

Charcot-Marie-Tooth disease type 1A (CMT1A) is a hereditary peripheral neuropathy, and its involvement in the central nervous system (CNS) is very rare. We herein report a 51-year-old woman with CMT1A who suffered from recurrent optic neuritis and myelopathy. Under the diagnosis of anti-aquaporin-4 antibody positive neuromyelitis optica spectrum disorder (NMOSD), we treated her successfully with corticosteroids. This is the first report of CMT1A complicated with AQP4-positive NMOSD. Although the coexistence of the two disorders may simply be a coincidence, we speculated that immune cross-reaction between overexpressed peripheral PMP22 protein and CNS myelin may have caused concomitant CMT1A and NMOSD.
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http://dx.doi.org/10.2169/internalmedicine.6153-20DOI Listing
December 2020

Contribution of chemotherapy to improved prognosis in stage 4 gastric cancer: trend analysis of a regional population-based cancer registry in Japan.

Int J Clin Oncol 2021 Feb 5;26(2):378-386. Epub 2020 Nov 5.

Division of Gastroenterology and Hepatology, Department of Internal Medicine (Omori), School of Medicine, Faculty of Medicine, Toho University, 6-11-1 Omorinishi, Ota-ku, Tokyo, 143-8541, Japan.

Objectives: Little is known about time trends in the prognosis of gastric cancer (GC), since the introduction of new chemotherapeutic agents. This study aimed to analyze how the increased number of available chemotherapeutic options affected the prognosis of GC and which patient types benefited within in a large population.

Methods: From a population-based cancer registry in Japan, 35,751 cases of GC were identified. Of these, 8214 cases were stage 4. The time trend for 3-year survival in stage 4 GC according to patient characteristics (age and tumor location) was estimated in relation to the introduction of new anticancer drugs. Multiple imputation was performed for sensitivity analysis to strengthen the missing data. In addition, we estimated the 5-year survival rate for distal-GC (DGC) and proximal-GC (PGC), and the hazard ratio (HR) was estimated by Cox proportional hazard model.

Results: Improvement of overall survival was accelerated in stage 4 cases over time. The prognosis was improved from 11.4% to 13.2%, subsequent to the approval of several oncologic drugs since 2009. Younger patients were more likely to have improved survival rates in response to the increase in chemotherapy options (< 60-year-old, 5.4%: 60-70, 2.2%; 70-80, 0.3%) from 2007 to 2015. The HR for DGC vs. PGC was 1.11 (95% CI 1.08-1.15), and PGC showed a higher rate of improved outcomes (2.4% vs. 0.6%).

Conclusions: This analysis showed that improvement in the GC survival rate was accelerated by the introduction of new chemotherapeutic strategies and it was most evident among younger patients and in patients with PGC.
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http://dx.doi.org/10.1007/s10147-020-01820-9DOI Listing
February 2021

Dislocation and oxygen-release driven delithiation in LiMnO.

Nat Commun 2020 Sep 8;11(1):4452. Epub 2020 Sep 8.

Institute of Engineering Innovation, University of Tokyo, Bunkyo, Tokyo, 113-8656, Japan.

Lithium-excess layered cathode materials such as LiMnO have attracted much attention owing to their high energy densities. It has been proposed that oxygen-release and cation-mixing might be induced by delithiation. However, it is still unclear as to how the delithiated-region grows. Here, by using atomic-resolution scanning transmission electron microscopy combined with electron energy-loss spectroscopy, we directly observe the atomic structures at the interface between pristine and delithiated regions in the partially delithiated LiMnO single crystal. We elucidate that the delithiated regions have extensive amounts of irreversible defects such as oxygen-release and Mn/Li cation-mixing. At the interface, a partially cation disordered structure is formed, where Mn migration occurred only in the specific Mn/Li layers. Besides, a number of dislocations are formed at the interface to compensate the lattice mismatch between the pristine and delithiated regions. The observed oxygen-release and dislocations could govern the growth of delithiated-regions and performance degradation in LiMnO.
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http://dx.doi.org/10.1038/s41467-020-18285-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479600PMC
September 2020

[Severe sensory-motor axonal neuropathy following diabetic ketoacidosis].

Rinsho Shinkeigaku 2020 Sep 8;60(9):614-619. Epub 2020 Aug 8.

Department of Neurology, Teikyo University School of Medicine.

We report a case of severe sensory-motor axonal neuropathy on the lower extremities associated with diabetic ketoacidosis (DKA). A sixteen-year-old boy developed coma and admitted to our hospital. We diagnosed him with DKA based on remarkable hyperglycemia, severe acidosis with hyperketonemia. Intensive glycemic control with insulin was immediately started. He had complications of heart failure, rhabdomyolysis, and renal failure, which required intensive care including mechanical ventilation and hemodialysis. When recovered from the critical condition, he noticed severe weakness, numbness, and pain on the lower limbs, and urinary retention. On nerve conduction studies, both motor and sensory action potentials were absent. Serum anti-ganglioside antibodies were negative. Albuminocytologic dissociation was evident in the cerebrospinal fluid. MRI study revealed marked gadolinium enhancement of the cauda equina. After high-dose intravenous immunoglobulin treatment, he was relieved from leg pain, but the leg weakness and bladder bowel dysfunction did not show immediate improvement. It took approximately six months until he became able to stand and walk using ankle orthosis. Acute neuropathy is a rare complication of diabetes mellitus. Painful neuropathy is known to emerge in association with diabetic treatment, but it seldom causes severe motor disturbance. On the other hand, motor-dominant polyneuropathy has been reported to occur acutely along the treatment of DKA and hyperosmolar hyperglycemia syndrome (HHS). Present case and previous cases with DKA and HHS suggest that rapid correction of glucose level is one of the underlying factors of acute neuropathy related with diabetic treatment.
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http://dx.doi.org/10.5692/clinicalneurol.cn-001433DOI Listing
September 2020

Split-finger syndrome in amyotrophic lateral sclerosis.

J Neurol Neurosurg Psychiatry 2020 11 30;91(11):1235-1236. Epub 2020 Jul 30.

Department of Neurology, Teikyo University School of Medicine, Itabashi-ku, Tokyo, Japan.

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http://dx.doi.org/10.1136/jnnp-2020-323986DOI Listing
November 2020

Glutamate-responsive translation of dendritic GSK3β mRNA triggers a cycle for amplification of reactivated preexisting GSK3β that is indispensable for tau hyperphosphorylation.

Neurochem Int 2020 10 23;139:104808. Epub 2020 Jul 23.

Laboratory of Biochemistry, School of Pharmacy, Nihon University, Narashinodai, Funabashi, Chiba, 274-8555, Japan. Electronic address:

The molecular mechanism responsible for hyperphosphorylated tau accumulation in dendrites of Alzheimer's disease (AD) neurons has not been fully clarified. Recently, we reported that tau mRNA is distributed into dendrites, and that translation and phosphorylation of tau protein are immediately enhanced in response to glutamatergic stimulation. Here, we focused on dendritic glycogen synthase kinase 3β (GSK3β), a key enzyme for tau phosphorylation, and investigated the mechanism responsible for the neural stimulation-induced hyperphosphorylation of the newly translated dendritic tau protein. We found that GSK3β mRNA was also distributed into dendrites of cultured hippocampal neurons, and that a glutamate-dependent slight increase of translation occurred in a short time. Concomitantly, dephosphorylation at the Ser9 residue of the preexisting GSK3β, which reactivates this kinase, was strongly induced without an increase of its phosphatase PP1 or a decrease of the PP1 inhibitor I-2. Instead, I-2 phosphorylation was observed, suggesting disinhibition of PP1. This glutamate-dependent phosphorylation of I-2 and the dephosphorylation of preexisting GSK3β were abolished in the presence of GSK3β inhibitors. Interestingly, translational obstruction of GSK3β mRNA also canceled these reactions. These results indicate that dendrites exhibit a glutamate-responsive cycle for amplification of reactivated preexisting GSK3β operating via PP1 disinhibition, whose activation requires neural activity-dependent translation of dendritic GSK3β mRNA. This would explain why a slight increase of dendritic GSK3β is sufficient to trigger hyperphosphorylation of significantly increased tau protein.
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http://dx.doi.org/10.1016/j.neuint.2020.104808DOI Listing
October 2020

[Survey of Methotrexate Prescription and Blood Concentration in Patients Treated with High-Dose Methotrexate].

Gan To Kagaku Ryoho 2020 Jul;47(7):1063-1067

Dept. of Pharmacy, The Institute of Medical Science Hospital, The University of Tokyo.

High-dose methotrexate therapy(HDMTX)is effective against lymphoid malignancies. However, delayed elimination of methotrexate(MTX)after HDMTX administration may lead to severe adverse drug reactions. We surveyed the drugs coadministered with MTX and the incidence of delayed MTX elimination in patients treated with HDMTX in a clinical setting. We analyzed the plasma MTX concentration in 110 samples after 55 cycles of HDMTX in 33 patients. Delayed MTX elimination was defined as a plasma MTX concentration ≥1.0 mmol/L at 48 h after the start of HDMTX administration or ≥0.1 mmol/L at 72 h after the start of HDMTX administration. The incidence of the combined use of drugs affecting MTX excretion and drugs that exhibited typical renal excretion was 84.8%(n=28). The incidence of delayed MTX elimination was 39.4%(n=13). MTX-induced acute kidney injury occurred in 9 patients, all of whom also exhibited delayed MTX elimination. Therefore, when prescribing HDMTX, it is important to monitor adverse events, including acute kidney injury, which may be induced by prolonged MTX blood concentrations.
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July 2020

Urgency Promotes Affective Disengagement: Effects From Bivalent Cues on Preference Formation for Abstract Images.

Front Psychol 2020 23;11:1404. Epub 2020 Jun 23.

Graduate School of Systems Life Sciences, Kyushu University, Fukuoka, Japan.

Although previous research has characterized the important role for spatial and affective pre-cues in the control of visual attention, less is known about the impact of pre-cues on preference formation. In preference formation, the gaze cascade phenomenon suggests that the gaze serves both to enhance and express "liking" during value-based decision-making. This phenomenon has been interpreted as a type of Pavlovian approach toward preferred objects. Decision-making here reflects a process of gradual commitment in which the gaze functions as a precursor to choice; by this account, overt attention produces a necessarily positive, additive effect on the value of the attended object. The implication is that drawing attention to an object should initiate, and therefore promote, preference formation for that object. Alternatively, information-integration models of attention propose that attention produces a multiplicative effect on the value of the attended object, implying that negative information can impede preference formation. To pitch the gradual-commitment hypothesis against the information-integration hypothesis, we conducted four experiments that combined the spatial-cueing paradigm with a value-based choice paradigm. In each trial in all experiments, subjects were presented with an irrelevant, peripheral pre-cue for a duration of 500 ms, followed by a 500 ms blank, and then a pair of abstract images (one at the pre-cued position; one in the opposite hemifield). The subjects were asked to choose their preferred abstract image by pressing the corresponding button. We manipulated the type of pre-cues (images of faces versus foods; with varying affective associations) and the time constraints (a deadline of 1,500 ms versus self-paced). Overall, the choice data showed a clear pattern of influence from the pre-cues, such that, given a deadline, abstract images were chosen less often if they had been preceded by a pre-cue with a negative affective association (both for face and food images). Analyses of the gaze data showed the emergence of significant gaze biases in line with the subjects' choices. Taken together, the data pattern provided support for the information-integration hypothesis, particularly under urgency. When tasked with a speeded preference choice, subjects showed affective disengagement following pre-cues that carried a negative association.
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http://dx.doi.org/10.3389/fpsyg.2020.01404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325338PMC
June 2020

Optimal Ratio of Carbon Flux between Glycolysis and the Pentose Phosphate Pathway for Amino Acid Accumulation in .

ACS Synth Biol 2020 07 30;9(7):1615-1622. Epub 2020 Jun 30.

Graduate School of Natural Science and Technology, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan.

Glucose is metabolized through central metabolic pathways such as glycolysis and the pentose phosphate pathway (PPP) to synthesize downstream metabolites including amino acids. However, how the split ratio of carbon flux between glycolysis and PPP specifically affects the formation of downstream metabolites remains largely unclear. Here, we conducted a comprehensive metabolomic analysis to investigate the effect of the split ratio between glycolysis and the PPP on the intracellular concentration of amino acids and their derivatives in . The split ratio was varied by exchanging the promoter of a gene encoding glucose 6-phosphate isomerase (PGI). The ratio was correlated with the transcription level and the enzyme activity. Concentrations of threonine and lysine-derivative 1,5-diaminopentane increased with an increase of the split ratio into the PPP. In contrast, concentrations of alanine, leucine, and valine were increased with an increase of the split ratio into glycolysis. These results could provide a new engineering target for improving the production of the amino acids and the derivatives.
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http://dx.doi.org/10.1021/acssynbio.0c00181DOI Listing
July 2020

Insulin and heparin challenge tests are useful for choosing an optimal insulin regimen in a case of subcutaneous insulin resistance.

J Diabetes Investig 2020 Sep 6;11(5):1370-1373. Epub 2020 May 6.

Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.

A 38-year-old woman with type 1 diabetes, whose fasting plasma glucose levels were >500 mg/dL under 176 U/day of subcutaneous insulin injection, was admitted to Nippon Medical School Hospital, Tokyo, Japan. When insulin was administered intravenously, she was able to maintain favorable glycemic control even under 24 U/day of regular insulin, showing that she was accompanied by subcutaneous insulin resistance. To choose an optimal insulin regimen, we carried out subcutaneous insulin challenge tests without or with heparin mixture, and found a cocktail of insulin lispro and heparin could reduce blood glucose levels markedly. As a consequence, she achieved favorable blood glucose control by continuous subcutaneous insulin infusion of the cocktail. In summary, the insulin and heparin challenge tests are useful for choosing an optimal insulin regimen in cases of subcutaneous insulin resistance.
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http://dx.doi.org/10.1111/jdi.13266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477523PMC
September 2020

Automatic Redirection of Carbon Flux between Glycolysis and Pentose Phosphate Pathway Using an Oxygen-Responsive Metabolic Switch in .

ACS Synth Biol 2020 04 23;9(4):814-826. Epub 2020 Mar 23.

Graduate School of Natural Science and Technology, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan.

Controlling the carbon flux into a desired pathway is important for improving product yield in metabolic engineering. After entering a cell, glucose is channeled into glycolysis and the pentose phosphate pathway (PPP), which decreases the yield of target products whose synthesis relies on NADPH as a cofactor. Here, we demonstrate redirection of carbon flux into PPP under aerobic conditions in , achieved by replacing the promoter of glucose 6-phosphate isomerase gene () with an anaerobic-specific promoter of the lactate dehydrogenase gene (). The promoter replacement increased the split ratio of carbon flux into PPP from 39 to 83% under aerobic conditions. The titer, yield, and production rate of 1,5-diaminopentane, whose synthesis requires NADPH as a cofactor, were increased by 4.6-, 4.4-, and 2.6-fold, respectively. This is the largest improvement in the production of 1,5-diaminopentane or its precursor, lysine, reported to date. After aerobic cell growth, expression was automatically induced under anaerobic conditions, altering the carbon flux from PPP to glycolysis, to produce succinate in a single metabolically engineered strain. Such an automatic redirection of metabolic pathway using an oxygen-responsive switch enables two-stage fermentation for efficient production of two different compounds by a single strain, potentially reducing the production costs and time for practical applications.
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http://dx.doi.org/10.1021/acssynbio.9b00493DOI Listing
April 2020

Abnormal evoked potentials in autoimmune glial fibrillary acidic protein astrocytopathy.

eNeurologicalSci 2020 Mar 10;18:100229. Epub 2020 Feb 10.

Department of Neurology, Fukushima Medical University, 1 Hikarigaoka, Fukushima, Fukushima 960-1295, Japan.

Autoimmune GFAP astrocytopathy is a new clinical entity and only a limited number of cases have been reported. Here we report the results of multimodal central conduction studies performed in a case of this disorder. A 72-year-old woman developed gradual cognitive decline and gait disturbance. A neurological examination revealed moderate amnesia, papilloedema, and pyramidal tract impairment of the bilateral lower limbs. The diagnosis of autoimmune GFAP astrocytopathy was made based on the typical MRI findings of periventricular radial linear gadolinium enhancement in the brain and longitudinally extensive lesions in the spinal cord, and anti-GFAP antibody detected in the cerebrospinal fluid. Somatosensory evoked potentials and transcranial magnetic stimulation studies revealed prolongation of conduction times. Visual evoked potentials showed an unusual W-shaped pattern. To our knowledge, this is the first neurophysiological demonstration of prolonged central conduction times in the autoimmune GFAP astrocytopathy. Further investigations are needed to establish the clinical value the neurophysiological examinations in this disorder.
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http://dx.doi.org/10.1016/j.ensci.2020.100229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026450PMC
March 2020

MRI Mapping of Muscle Denervation in Metastatic Myelopathy.

Intern Med 2020 04 9;59(8):1113-1114. Epub 2020 Jan 9.

Department of Neurology, Fukushima Medical University, Japan.

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http://dx.doi.org/10.2169/internalmedicine.3944-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7205537PMC
April 2020

Enhanced Tau Protein Translation by Hyper-Excitation.

Front Aging Neurosci 2019 20;11:322. Epub 2019 Nov 20.

Laboratory for Alzheimer's Disease, Department of Life Science, Faculty of Science, Gakushuin University, Tokyo, Japan.

Tau is a microtubule-associated protein, localizing mainly in the axon of mature neurons. Phenotypic analysis of knockout mice has revealed an impairment of synaptic plasticity but without gross changes in brain morphology. Since we previously described the presence of tau mRNA in the somatodendritic compartment, including the postsynapse, and demonstrated that it could be locally translated in response to glutamate, it appears that the regulated translation of synaptic tau can have a direct impact on synaptic function. Using SH-SY5Y cells, we herein confirm that glutamate dose-dependently regulates the translation of tau protein without altering tau mRNA levels. This is supported by the finding that cycloheximide blocks glutamate-stimulated increases in tau protein levels. Our observation that neural excitation can directly upregulate tau mRNA translation helps explain the pathological accumulation of tau in the somatodendrite.
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http://dx.doi.org/10.3389/fnagi.2019.00322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879554PMC
November 2019

Preoperative growth hormone (GH) peak values during a GH releasing peptide-2 test reflect the severity of hypopituitarism and the postoperative recovery of GH secretion in patients with non-functioning pituitary adenomas.

Endocr J 2020 Feb 26;67(2):167-175. Epub 2019 Nov 26.

Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, Tokyo 113-8603, Japan.

Non-functioning pituitary adenoma (NFPA) is one common cause of adult growth hormone deficiency (AGHD). In Japan, a GH-releasing peptide (GHRP)-2 test is used to evaluate GH secretion. Although the cut-off for peak GH during a GHRP-2 test for severe AGHD is ≤9 ng/mL, severe AGHD may further diminish responses (range, nearly no-response to ≤9 ng/mL). We studied whether the peak GH responses during a GHRP-2 test could be predicted based on clinical characteristics of patients with NFPA. We compared patients with almost no-response during a GHRP-2 test with other patients considered as severe AGHD. Among the 76 patients with NFPA who were admitted to our institution, 36 patients (mean age, 61 years; male/female, n = 23/n = 13) were diagnosed with severe AGHD based on a preoperative GHRP-2 test. Based on the preoperative median peak GH concentration (2.83 ng/mL), patients were divided into two groups (
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http://dx.doi.org/10.1507/endocrj.EJ19-0288DOI Listing
February 2020

A patient with McLeod syndrome showing involvement of the central sensorimotor tracts for the legs.

BMC Neurol 2019 Nov 27;19(1):301. Epub 2019 Nov 27.

Department of Neurology, Fukushima Medical University, Fukushima, Japan.

Background: McLeod syndrome is a rare X-linked recessive acanthocytosis associated with neurological manifestations including progressive chorea, cognitive impairment, psychiatric disturbances, seizures, and sensorimotor axonal polyneuropathy. However, no studies have investigated the functioning of central sensorimotor tracts in patients with McLeod syndrome.

Case Presentation: A 66-year-old man had experienced slowly progressive chorea and gait disturbance due to lower limb muscle weakness since his early fifties. Blood examinations showed erythrocyte acanthocytosis and the reduction of Kell antigens in red blood cells. Brain magnetic resonance imaging showed atrophy of the bilateral caudate nuclei and putamen. The diagnosis of McLeod syndrome was confirmed by the presence of a mutation of the XK gene on the X chromosome. Somatosensory-evoked potential and transcranial magnetic stimulation studies demonstrated that the central sensory and motor conduction times were abnormally prolonged for the lower extremity but normal for the upper extremity.

Conclusions: This is the first report of the involvement of the central sensorimotor tracts for the legs in a patient with McLeod syndrome. The clinical neurophysiological technique revealed the central sensorimotor tracts involvements clinically masked by neuropathy.
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http://dx.doi.org/10.1186/s12883-019-1526-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882147PMC
November 2019

Diagnostic yield of the Japan NBI Expert Team (JNET) classification for endoscopic diagnosis of superficial colorectal neoplasms in a large-scale clinical practice database.

United European Gastroenterol J 2019 08 26;7(7):914-923. Epub 2019 Apr 26.

Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan.

Background: Magnifying Narrow Band Imaging (NBI) during colonoscopy is a reliable method for differential and depth diagnoses of colorectal lesions. This study examined the diagnostic yield of magnifying NBI based on the Japan NBI Expert Team (JNET) classification in a clinical setting using a large-scale clinical practice database. Types 1, 2A, 2B and 3 correspond to the histopathological classifications of hyperplastic polyp/sessile-serrated polyp, low-grade intramucosal neoplasia, high-grade intramucosal neoplasia/shallow submucosal invasive cancer, and deep submucosal invasive cancer, respectively.

Methods: The prospective records of colonoscopy reports and pathological data of 1558 consecutive superficial colorectal lesions removed by colonoscopy were retrospectively analysed. After excluding 156 lesions, the documented JNET classifications of the remaining 1402 colorectal lesions were analysed. Diagnostic yield was analysed and also compared between expert endoscopists and nonexpert endoscopists.

Results: The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were respectively 75%, 96%, 74%, 96% and 93% for type 1; 91%, 70%, 92%, 67% and 87% for type 2A; 42%, 95%, 26%, 98% and 93% for type 2B; and 35%, 100%, 93%, 98% and 98% for type 3. Nonexpert and expert endoscopists alike had specificity, NPV and accuracy >90% for types 1, 2B and 3, and a sensitivity and PPV >90% for type 2A. Type 2B had a low sensitivity of 42% because it included various histological features.

Conclusions: The JNET classification proved useful in a clinical setting both for expert and nonexpert endoscopists, as was expected from the original JNET definition, but type 2B requires further investigation using pit pattern diagnosis.
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http://dx.doi.org/10.1177/2050640619845987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683640PMC
August 2019

Primate prefrontal neurons signal economic risk derived from the statistics of recent reward experience.

Elife 2019 07 25;8. Epub 2019 Jul 25.

Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.

Risk derives from the variation of rewards and governs economic decisions, yet how the brain calculates risk from the frequency of experienced events, rather than from explicit risk-descriptive cues, remains unclear. Here, we investigated whether neurons in dorsolateral prefrontal cortex process risk derived from reward experience. Monkeys performed in a probabilistic choice task in which the statistical variance of experienced rewards evolved continually. During these choices, prefrontal neurons signaled the reward-variance associated with specific objects ('object risk') or actions ('action risk'). Crucially, risk was not derived from explicit, risk-descriptive cues but calculated internally from the variance of recently experienced rewards. Support-vector-machine decoding demonstrated accurate neuronal risk discrimination. Within trials, neuronal signals transitioned from experienced reward to risk (risk updating) and from risk to upcoming choice (choice computation). Thus, prefrontal neurons encode the statistical variance of recently experienced rewards, complying with formal decision variables of object risk and action risk.
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http://dx.doi.org/10.7554/eLife.44838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658165PMC
July 2019

Efficacy of Full-Spectrum Endoscopy to Visualize the Major Duodenal Papilla in Patients with Familial Adenomatous Polyposis.

Digestion 2020 16;101(5):563-570. Epub 2019 Jul 16.

Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.

Background And Aims: Duodenal cancer is one of the extracolonic malignancies with known mortality in familial adenomatous polyposis (FAP) patients. Visualization of the major duodenal papilla (MDP) with a standard esophagogastroduodenoscopy (EGD) is currently insufficient because of the limited field of view. Full-spectrum endoscopy (FUSE), utilizing double imagers located on the front and side of the endoscopic tip, provides a wider field of view up to 245 degrees. The aim of this study was to evaluate the efficacy of FUSE in visualizing MDP in patients with FAP.

Methods: This study was a single-center retrospective study including 49 FAP patients undergoing surveillance at our institution. EGD was performed by qualified endoscopists using FUSE, and visibility of the MDP was evaluated. All examinations were video-recorded, and the clips for individual patient were edited to forward view images alone (conventional group) and 2-view images of the duodenum (forward and side-view [FUSE group]). Three other qualified external endoscopists independently reviewed the videos and compared the visibility of MDP between the conventional and the FUSE groups. Primary endpoint was the rate of Type 1 visibility (whole area of the papilla) in off-site video reviews. We also assessed MDP visibility on-site as secondary endpoint.

Results: The rate of type 1 MDP visibility was significantly higher in the FUSE group than conventional group in both on-site (32.6/100%, p < 0.001) and off-site reviews (8.2, 16.3, 14.3/100, 98, and 100%, p < 0.001).

Conclusions: FUSE is recommended in screening and surveillance EGD to better visualize MDP in FAP patients.
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http://dx.doi.org/10.1159/000501476DOI Listing
July 2019

Transition-Metal Distribution in Brownmillerite CaFeCoO.

Inorg Chem 2019 Aug 11;58(15):10209-10216. Epub 2019 Jul 11.

Institute of Engineering Innovation , University of Tokyo , Bunkyo , Tokyo 113-8656 , Japan.

CaFeCoO (0 ≤ ≤ 1) with higher Co content, which crystallizes in a brownmillerite-type structure, is currently one of the best oxygen-evolution-reaction (OER) catalysts. Identifying the Fe/Co occupancies at the octahedral () and tetrahedral () sites in the structure is the foundation for the understanding of the role of cobalt in each site and the exploration of further improvement in the OER activity. Here, we investigate the Fe/Co distribution in CaFeCoO by means of atomic-resolution energy dispersive X-ray spectroscopy in scanning transmission electron microscopy and dynamical image simulations combined with systematic density functional theory calculations. Our careful microscopic study reveals the absence of long-range Fe/Co order within the transition-metal (TM) layers, but cobalt is slightly enriched at the and sites in the as-synthesized (1100 °C) and 800 °C annealed for a month samples, respectively. The observed Co site preferences are interpretable from the viewpoints of TM ionic size effect and ligand field effect, which are competitive around a crossover point at a certain temperature between 800 and 1100 °C. We also elucidate that the as-synthesized sample with Co enrichment at the site shows the better OER activity, and the optimum annealing temperature for more OER active CaFeCoO should be higher than the crossover temperature.
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http://dx.doi.org/10.1021/acs.inorgchem.9b01356DOI Listing
August 2019

A case of mixed-type early gastric cancer with recurrence following curative endoscopic submucosal dissection for expanded indication.

Endosc Int Open 2019 Jun 12;7(6):E841-E845. Epub 2019 Jun 12.

Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan.

In Japan, intramucosal gastric adenocarcinoma with ulcerative finding having a predominantly differentiated type with an undifferentiated component, tumor diameter ≤ 3 cm, and no lymphovascular invasion is included in the expanded pathological criteria for curative endoscopic treatment. This indication is based on retrospective examination of surgical resection cases, and is determined to have a negligible risk of lymph node metastasis (LNM). We performed endoscopic submucosal dissection on a 78-year-old man with early gastric cancer in 2011, and pathology revealed a well-differentiated tubular adenocarcinoma (21 × 10 mm in diameter), with poorly differentiated adenocarcinoma components, limited to the mucosa, fibrosis by ulcer scar in the submucosal layer, no lymphovascular invasion, and tumor-free margins. Resection was determined to be curative under expanded indications of the gastric cancer treatment guidelines, 4 edition. However, 55 months after the initial diagnosis, invasive local and distant recurrence was noted. Ultimately, the patient died of gastric cancer 3 months after recurrence.
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http://dx.doi.org/10.1055/a-0900-3835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6561759PMC
June 2019

A Case of Gitelman Syndrome that Was Difficult to Distinguish from Hypokalemic Periodic Paralysis Caused by Graves' Disease.

J Nippon Med Sch 2019 Dec 17;86(5):301-306. Epub 2019 May 17.

Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School.

A 21-year-old man presented with hyperthyroidism and hypokalemia and was treated for thyrotoxic hypokalemic periodic paralysis caused by Graves' disease. Thyroid function soon normalized but hypokalemia persisted. Laboratory data revealed hyperreninemic hyperaldosteronism and metabolic alkalosis consistent with Gitelman Syndrome. The patient was found to have a previously unreported compound heterozygous mutation of T180K and L858H in the SLC12A3 gene, and Gitelman Syndrome was diagnosed. He was started on eplerenone to control serum potassium level. Alternative diagnoses should be considered when electrolyte imbalances persist after disease resolution.
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http://dx.doi.org/10.1272/jnms.JNMS.2019_86-505DOI Listing
December 2019

Evaluative Processing of Food Images: Longer Viewing for Indecisive Preference Formation.

Front Psychol 2019 20;10:608. Epub 2019 Mar 20.

Graduate School of Systems Life Sciences, Kyushu University, Fukuoka, Japan.

The well-known gaze cascade hypothesis proposes that as people look longer at an item, they tend to show an increased preference for it. However, using single food images as stimuli, we recently obtained results that clearly deviated from the general proposal that the gaze both expresses and influences preference formation. Instead, the pattern of data depended on the self-determination of exposure duration as well as the type of evaluation task. In order to disambiguate how the type of evaluation determines the relationship between viewing and liking we conducted the present follow-up study, with a fixed response set size as opposed to the varying set sizes in our previous study. In non-exclusive evaluation tasks, subjects were asked how much they liked individual food images. The recorded response was a number from 1 to 3. In exclusive evaluation tasks, subjects were asked for each individual food image to give one of three response options toward a limited selection: include it, exclude it, or defer the judgment. When subjects were able to determine the exposure duration, both the non-exclusive and exclusive evaluations produced inverted U-shaped trends such that the polar ends of the evaluation (the positive and negative extremes) were associated with relatively short viewing times, whereas the middle category had the longest viewing times. Thus, the data once again provided firm evidence against the notion that longer viewing facilitates preference formation. Moreover, the fact that non-exclusive and exclusive evaluation produced similar inverted U-shaped patterns suggests that the response set size is the critical factor that accounts for the observations here versus in our previous study. When keeping the response set size constant, with an equal opportunity to observe inverted U-shaped patterns, the findings are suggestive of a role for the level of decisiveness in determining the length of viewing time. For items that can be categorically identified as positive or negative, the evaluations are soon completed, with relatively brief viewing times. The prolonged visual inspection for the middle category may reflect doubt or uncertainty during the evaluative processing, possibly with an increased effort of information integration before reaching a conclusion.
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http://dx.doi.org/10.3389/fpsyg.2019.00608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6435591PMC
March 2019

Assessment of Cognitive and Motor Skills in Parkinson's Disease by a Robotic Object Hitting Game.

Front Neurol 2019 28;10:19. Epub 2019 Jan 28.

Department of Neurology, School of Medicine, Fukushima Medical University, Fukushima, Japan.

Parkinson's disease (PD) patients experience various symptoms including extrapyramidal motor disturbances and cognitive impairments, which cause difficulties in daily life. However, PD patients have rarely been studied under realistic task situations that require high-level interaction of cognitive and motor skills. The aim of this study was to investigate the contribution of cognitive and motor factors to the performance of PD patients under high cognitive and kinematic loads. Twenty-six PD patients and 14 control subjects participated in the study. The PD patients performed a task involving hitting targets and avoiding distractors in levodopa On and Off states. A robotic manipulandum device recorded the numbers of target and distractor hits and hand kinematics, including movement area and speed. Performance on standard cognitive batteries and the Movement Disorder Society - Unified Parkinson's Disease Rating Scale motor scores were examined. The results indicated that the PD patients hit significantly fewer targets and more distractors than did the controls ( < 0.05). In PD patients, the average hand speed was slower and the area of hand movement was smaller than those of the control subjects ( < 0.001). Levodopa significantly increased the average hand speed and movement area ( < 0.01), but levodopa had an insignificant effect on the number of correct targets hit and erroneous distractor hits. The scores of cognitive batteries predicted the performance with regard to both targets hit and distractor avoidance. Our results were indicative of a dynamic interaction between cognitive and kinematic skills while the PD patients performed a virtual reality game. Single-dose levodopa enhanced kinematic capacity, and the global intelligence level predicted game performance.
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http://dx.doi.org/10.3389/fneur.2019.00019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6360146PMC
January 2019