A5103109202- Influenza Virus Research Studies
- Muscle activation and electromyography studies
- Respiratory viral infections research
- interferon and immune responses
- Neuroscience and Neural Engineering
- Motor Control and Adaptation
- EEG and Brain-Computer Interfaces
- Urban and spatial planning
- Viral Infections and Immunology Research
- RNA and protein synthesis mechanisms
- Transcranial Magnetic Stimulation Studies
- Color Science and Applications
- Antifungal resistance and susceptibility
- Image Enhancement Techniques
- Research on Leishmaniasis Studies
- Advanced Sensor and Energy Harvesting Materials
- Veterinary Orthopedics and Neurology
- Trypanosoma species research and implications
- Congenital Diaphragmatic Hernia Studies
- Fungal Infections and Studies
- Animal Disease Management and Epidemiology
- Virology and Viral Diseases
- Shoulder Injury and Treatment
- Neurogenesis and neuroplasticity mechanisms
- Industrial Vision Systems and Defect Detection
Yamagata University
2004-2024
Shionogi (Japan)
2015-2022
Futaba (Japan)
2015-2021
Hokkaido Research Organization
2019-2021
Institute of Virology of the Slovak Academy of Sciences
2007
Shinshu University
1985-2003
Tokyo Polytechnic University
1996
Nagoya City University
1994
University of the Ryukyus
1993
Ōtani University
1987-1990
Abstract Baloxavir acid (BXA), derived from the prodrug baloxavir marboxil (BXM), potently and selectively inhibits cap-dependent endonuclease within polymerase PA subunit of influenza A B viruses. In clinical trials, single doses BXM profoundly decrease viral titers as well alleviating symptoms. Here, we characterize impact on BXA susceptibility replicative capacity variant viruses detected in post-treatment monitoring studies. We find that I38T substitution is a major pathway for reduced...
Cap-dependent endonuclease (CEN) resides in the PA subunit of influenza virus and mediates critical "cap-snatching" step viral RNA transcription, which is considered to be a promising anti-influenza target. Here, we describe vitro characterization novel CEN inhibitor, baloxavir acid (BXA), active form marboxil (BXM). BXA inhibits transcription via selective inhibition activity enzymatic assays, replication infected cells without cytotoxicity cytopathic effect assays. The antiviral also...
Hepatitis B virus (HBV) is a major human pathogen that chronically infects approximately 350 million people, causing liver disease and cancer. HBV virions bud into an endoplasmic reticulum (ER)-associated intracellular compartment, but the mechanisms of assembly, budding, release remain poorly understood. Budding retroviruses some other enveloped RNA viruses from plasma membranes requires host functions involved in protein sorting late endosomal multivesicular bodies (MVBs). To determine...
A multichannel functional electrical stimulation (FES) system for the restoration of quadriplegic upper extremity function is described. The composed a personal computer, peripheral electronic circuits, CRT display and respiratory sensors volitional control by patient, percutaneous electrodes. In this system, versatile realized controlling memory allocation stored data voluntary signals, sophisticated fine fingers, wrists, elbow creating from recorded myoelectric activities normal subjects...
Baloxavir marboxil (formerly S-033188) is a first-in-class, orally available, cap-dependent endonuclease inhibitor licensed in Japan and the USA for treatment of influenza virus infection. We evaluated efficacy delayed oral with baloxavir combination neuraminidase mouse model lethal infection.The inhibitory potency acid (the active form marboxil) inhibitors was tested vitro. The therapeutic effects oseltamivir phosphate, or combinations thereof, were mice lethally infected A/PR/8/34;...
Baloxavir marboxil (BXM) is an orally available small molecule inhibitor of cap-dependent endonuclease (CEN), essential enzyme in the initiation mRNA synthesis influenza viruses. In present study, we evaluated efficacy BXM against virus infection mouse models. Single-day oral administration completely prevented mortality due to with A and B mice. Moreover, 5-day repeated was more effective for reducing body weight loss mice infected than oseltamivir phosphate (OSP), even when treatment...
Abstract Human infections with avian-origin influenza A(H7N9) virus represent a serious threat to global health; however, treatment options are limited. Here, we show the inhibitory effects of baloxavir acid (BXA) and its prodrug marboxil (BXM), first-in-class cap-dependent endonuclease inhibitor, against A(H7N9), in vitro vivo . In cell culture, BXA at four nanomolar concentration achieved 1.5–2.8 log reduction titers including NA-R292K mutant highly pathogenic avian viruses, whereas NA...
Abstract Background Baloxavir marboxil (BXM) is an approved drug that selectively targets cap‐dependent endonuclease on PA subunit in the RNA polymerase complex of influenza A and B viruses. Amino acid substitutions at position 38 were identified as a major pathway for reduced susceptibility to baloxavir (BXA), active form BXM. Additionally, found positions E23, A37, E199 impact BXA by less than 10‐fold. Methods We comprehensively evaluated novel amino PA, PB1, PB2 subunits BXM clinical...
Invasive fungal infections (IFIs) are fatal infections, but treatment options limited. The clinical efficacies of existing drugs unsatisfactory because side effects, drug–drug interaction, unfavorable pharmacokinetic profiles, and emerging drug-resistant fungi. Therefore, the development antifungal with a new mechanism is an urgent issue. Herein, we report novel aryl guanidine agents, which inhibit target enzyme in ergosterol biosynthesis pathway. Structure–activity relationship property...
Human infections caused by the H5 highly pathogenic avian influenza virus (HPAIV) sporadically threaten public health. The susceptibility of HPAIVs to baloxavir acid (BXA), a new class inhibitors for cap-dependent endonuclease, has been confirmed in vitro, but it not yet fully characterized. Here, efficacy BXA against HPAIVs, including recent H5N8 variants, was assessed vitro. antiviral marboxil (BXM) H5N1 virus-infected mice also investigated. exhibited similar vitro activities H5N1, H5N6,...
Viral hemorrhagic fevers caused by members of the order Bunyavirales comprise endemic and emerging human infections that are significant public health concerns. Despite disease severity, there few therapeutic options available, therefore effective antiviral drugs urgently needed to reduce burdens. Bunyaviruses, like influenza viruses (IFVs), possess a cap-dependent endonuclease (CEN) mediates critical cap-snatching step viral RNA transcription. We screened compounds from our CEN inhibitor...
Aspergillus flavus is the second most significant pathogenic cause of invasive aspergillosis; however, its emergence risks and mechanisms voriconazole (VRC) resistance have not yet been elucidated in detail. Here, we demonstrate that repeated exposure A. to subinhibitory concentrations VRC vitro causes a VRC-resistant mutant with novel mechanism.
HANDA, Y., NAITO, A., WATANABE, S., KOMATSU, S. and SHIMIZU, Y. Functional Recovery of Locomotive Behavior in the Adult Spinal Dog. Tohoku J. exp. Med., 1986, 148 (4), 373-384-Complete transection midthoracic spinal cord was performed on adult female dogs. Development reflexes locomotive movements hindlimbs after investigated over several months. In earlier stages surgery, dogs showed flaccid paralysis hindlimbs. Within weeks, muscle tone gradually increased accompanied by development...
Preimplantation genomic selection using estimated breeding values (GEBVs) based on single nucleotide polymorphism (SNP) genotypes is expected to accelerate genetic improvement in cattle. To develop a preimplantation system for carcass traits Japanese Black cattle, we investigated the accuracy of evaluation biopsied embryonic cells (Experiment 1); also performed an empirical embryo transfer (ET) vitrified GEBV-evaluated blastocysts assess efficiency 2). In Experiment 1, mean call rate SNP...
Baloxavir acid, the active form of orally available prodrug baloxavir marboxil, is a novel cap-dependent endonuclease inhibitor influenza virus. marboxil has been shown to rapidly reduce virus titres compared with oseltamivir in clinical studies.We investigated relationship between pharmacokinetic (PK) parameters and antiviral activity acid based on titre reduction lungs infected mice.BALB/c mice sub-lethal dose A(H1N1), A(H1N1)pdm09, A(H3N2) or type B were treated day 5 oral (0.5-50 mg/kg...
Activities of the elbow flexors (biceps brachii, BB; brachialis, B; brachioradialis, BR) and extensors (triceps TB) in a motion forearm pronation/supination with maintenance flexion (PS-movement) nine healthy human subjects were studied by electromyography (EMG). The subject performed PS-movement slowly or quickly without load extending elbow. In slow PS-movement, an increase decrease EMG activities during supination pronation, respectively, seen BB reverse was B. A clear increment...
Activities of the elbow flexors and extensors during movement flexion extension were analyzed in six normal human volunteers by electromyography (EMG). In flexors, majority muscles showed EMG activities both phases, although patterns amplitudes varied from individual to individual. The biceps brachii always became less active when forearm was pronation. extensors, increase observed at period maximum cases, while no activity shown throughout some cases. During except extension, triceps almost...
Abstract Background S-033447, an active form of orally available prodrug S-033188, is a novel small molecule inhibitor cap-dependent endonuclease that essential for influenza virus transcription and replication. In this study, we evaluated the inhibitory effect S-033188 in combination with neuraminidase inhibitors on replication A/H1N1 cultured cells. Methods The effects S-033447 NA cytopathic A/PR/8/34 strain Madin–Darby canine kidney cells 2 days were tested EC50 determined. index (CI),...
NAITO, A., YAJIMA, M., FUKAMACHI, H., USHIKOSHI, K., SUN, Y.-J. and SHIMIZU, Y. Electromyographic (EMG) Study of the Elbow Flexors during Supination Pronation Forearm. Tohoku J. Exp. Med., 1995, 175 (4), 285-288 - Activities elbow flexors supination pronation forearm in a normal human volunteer were studied by an electromyography (EMG). The performed movement slowly or quickly holding flexion at various angles with without load. biceps brachii showed increase decrease EMG activities...