A5039144227- Prion Diseases and Protein Misfolding
- Neurological diseases and metabolism
- Monoclonal and Polyclonal Antibodies Research
- Lymphoma Diagnosis and Treatment
- RNA regulation and disease
- Trace Elements in Health
- HIV Research and Treatment
- RNA Research and Splicing
- Alzheimer's disease research and treatments
- Neuroscience and Neuropharmacology Research
- RNA Interference and Gene Delivery
- Chronic Lymphocytic Leukemia Research
- Bacteriophages and microbial interactions
- Antimicrobial Peptides and Activities
- Animal Disease Management and Epidemiology
- Neuroinflammation and Neurodegeneration Mechanisms
- Medicinal Plants and Neuroprotection
- T-cell and Retrovirus Studies
- Viral-associated cancers and disorders
- Biochemical Acid Research Studies
- Alcoholism and Thiamine Deficiency
- Chemical and Physical Properties in Aqueous Solutions
- Advanced Drug Delivery Systems
- interferon and immune responses
- Computational Drug Discovery Methods
Fukuoka University
2002-2024
Nagasaki University
2012-2021
Saiseikai Ibaraki Hospital
2016
Yokohama City University Medical Center
2013-2015
Yokohama City University
2013-2015
Hiratsuka City Hospital
2013-2014
Tokyo Metropolitan Government
2012
Japan Science and Technology Agency
2006
Japanese Society of Tropical Medicine
2006
Prion diseases are fatal neurodegenerative disorders and no effective treatment has been established to date. In this study, we evaluated the effect of FK506 (tacrolimus), a macrolide that is known be mild immunosuppressant, on prion infection, using cell culture animal models. We found markedly reduced abnormal form protein (PRNPSc) in cultures (N2a58 MG20) infected with Fukuoka-1 prion. The levels autophagy-related molecules such as LC3-II, ATG12–ATG5 ATG7 were significantly increased...
The prion-like seeding of misfolded α-synuclein (αSyn) involved in the pathogenesis Lewy body diseases (LBD) remains poorly understood at molecular level. Using real-time quaking-induced conversion (RT-QUIC) assay, we investigated whether brain tissues from cases dementia with bodies (DLB), which contain serine 129 (Ser129)-phosphorylated insoluble aggregates αSyn, can convert Escherichia coli-derived recombinant αSyn (r-αSyn) to fibrils. Diffuse neocortical DLB yielded 50% dose (SD50)...
Prion diseases are characterized by the accumulation of amyloid fibrils. The causative agent is an infectious that comprises solely misfolded prion protein (PrP
We present an extensive study on inhomogeneous chiral condensates in QCD at finite density the limit using a generalized Ginzburg-Landau (GL) approach. Performing analyses higher harmonics of one-dimensionally (1D) modulated condensates, we numerically confirm previous claim that solitonic condensate characterized by Jacobi's elliptic function is most favorable structure 1D modulations. then investigate possibility realization several multidimensional modulations within same framework. also...
The tumor microenvironment, including tumor-infiltrating lymphocytes and myeloid-derived cells, is an important factor in the pathogenesis clinical behavior of malignant lymphoma. However, prognostic significance peripheral monocytes lymphoma remains unclear.We evaluated impact absolute lymphocyte count (ALC), monocyte (AMC), lymphocyte/monocyte ratio (LMR) 359 diffuse large B-cell (DLBCL) patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone...
Abstract Prion diseases are fatal neurodegenerative disorders characterized by the accumulation of prion protein (PrP C ). To date, there is no effective treatment for disease. The accumulated PrP, termed PrP Sc , forms amyloid fibrils and could be infectious. It has been suggested that abnormally folded resistant to proteolytic degradation also inhibits proteasomal functions in infected cells, thereby inducing neuronal death. Recent work indicates ubiquitin-proteasome system involved...
Prion diseases are neurodegenerative disorders characterized by the aggregation of abnormally folded prion protein (PrPSc). In this study, we focused on mechanism clearance PrPSc, which remains unclear. p62 is a cytosolic known to mediate both formation and degradation aggregates abnormal proteins. The levels increased in prion-infected brains persistently infected cell cultures. Upon proteasome inhibition, co-localized with forming large aggregate perinuclear region, hereafter referred as...
The Sokal and Hasford scores were developed in the chemotherapy interferon era are widely used as prognostic indicators patients with chronic myeloid leukemia (CML). Recently, a new European Treatment Outcome Study (EUTOS) scoring system was developed. We performed multicenter retrospective study to validate effectiveness of each three systems. cohort included 145 diagnosed CML phase who treated imatinib. In EUTOS low- high-risk groups, cumulative incidence complete cytogenetic response...
ABSTRACT The phenomenon of prion strains with distinct biological characteristics has been hypothesized to be involved in the structural diversity abnormal protein (PrP Sc ). However, molecular basis transmission strain properties remains poorly understood. Real-time quaking-induced conversion (RT-QUIC) is a cell-free system that uses Escherichia coli -derived recombinant PrP (rPrP) for sensitive detection . To investigate whether various can transmitted amyloid fibrils consisting rPrP (rPrP...
Influenza virus infections are serious public health concerns throughout the world. The development of compounds with novel mechanisms action is urgently required due to emergence viruses resistance currently-approved anti-influenza viral drugs. We performed in silico screening using a structure-based drug discovery algorithm called Nagasaki University Docking Engine (NUDE), which optimised for GPU-based supercomputer (DEstination Gpu Intensive MAchine; DEGIMA), by targeting influenza PA...
Summary Introduction The prognostic value of serum ferritin level in patients with peripheral T‐cell lymphoma ( PTCL ) remains unknown. Methods We retrospectively analyzed clinical data from 78 consecutive newly diagnosed that were treated anthracycline‐containing regimens between 1998 and 2011. Results consisted 50 males 28 females a median age 64 years (range, 16–83 years). subtypes 39 , not otherwise specified angioimmunoblastic AITL ). observation period for the surviving was months....
Abstract Accidental transmission of prions during neurosurgery has been reported as a consequence re-using contaminated surgical instruments. Several decontamination methods have studied using the 263K-hamster prion; however, no studies directly evaluated human prions. A newly developed in vitro amplification system, designated real-time quaking-induced conversion (RT-QuIC), allowed activity abnormal prion proteins to be assessed within few days. RT-QuIC recombinant protein (PrP) showed high...
Infectious prions comprising abnormal prion protein, which is produced by structural conversion of normal are responsible for transmissible spongiform encephalopathies including Creutzfeldt-Jakob disease in humans. Prions infectious agents that do not possess a genome and the pathogenic protein was thought to evoke any immune response. Although we previously reported interferon regulatory factor 3 (IRF3) likely be involved pathogenesis diseases, suggesting protective role host innate...
ABSTRACT Abnormal prion protein (PrP Sc ) generated from the cellular isoform of PrP C is assumed to be main or sole component pathogen, called prion, transmissible spongiform encephalopathies (TSE). Because a host-encoded protein, acquired immune responses are not induced in TSE. Meanwhile, activation innate system has been suggested partially block progression TSE; however, mechanism well understood. To further elucidate role infection, we investigated function interferon regulatory factor...
LL-37, a well-known antimicrobial human peptide, is cationic peptide that provides an important defense mechanism in damaged skin. Accumulating evidence indicates LL-37 also displays anticancer effect colon cancer, gastric hematologic malignancy and oral squamous cell carcinoma. However, activity of fragment analogs has not been reported. Poor intercellular translocation may be one the causes for this lack observed activity. In study, analog with cysteine at N -terminus was conjugated...
Prion diseases are neurodegenerative disorders caused by the accumulation of abnormal prion protein (PrPSc) in central nervous system. With aim elucidating mechanism underlying and degradation PrPSc, we investigated role autophagy its degradation, using cultured cells stably infected with distinct strains. The effects pharmacological compounds that inhibit or stimulate cellular signal transduction pathways mediate during PrPSc were evaluated. persistently strain Fukuoka-1 (FK), derived from...
The infectious agents of the transmissible spongiform encephalopathies are composed amyloidogenic prion protein, PrPSc. Real-time quaking-induced conversion can amplify very small amounts PrPSc seeds in tissues/body fluids patients or animals. Using this vitro PrP-amyloid amplification assay, we quantitated seeding activity affected human brains. End-point assay using serially diluted brain homogenates sporadic Creutzfeldt-Jakob disease demonstrated that 50% dose (SD50) is reached...
This study evaluated the efficacy of central nervous system (CNS) prophylaxis using intrathecal methotrexate (IT-MTX) in patients with diffuse large B-cell lymphoma (DLBCL). We retrospectively studied 322 who achieved first complete remission (CR) after rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. The CNS consisted four doses IT-MTX (15 mg) hydrocortisone (25 administered CR was achieved. Forty (12%) received (group A) 282 (88%) did not B)....
Abnormal forms of prion protein (PrP(Sc)) accumulate via structural conversion normal PrP (PrP(C)) in the progression transmissible spongiform encephalopathy. Under cell-free conditions, process can be efficiently replicated using vitro PrP(Sc) amplification methods, including misfolding cyclic amplification. These methods enable ultrasensitive detection PrP(Sc); however, there remain difficulties utilizing them practice. For example, to date, several rounds have been necessary reach maximal...