255 results on '"T. Uto"'
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2. Postoperative motor dysfunction in the lower extremities after total en bloc spondylectomy for lumbar spinal tumors: A prospective longitudinal cohort study
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S. Kato, N. Yokogawa, T. Shimizu, S. Nagatani, M. Kawai, T. Uto, Y. Ishino, K. Nampo, and S. Demura
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Neurology. Diseases of the nervous system ,RC346-429 - Published
- 2024
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3. Association between intratumoral flow void and intraoperative blood loss in metastatic spinal tumor surgery
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Y. Ishino, S. Kato, N. Yokogawa, T. Shimizu, S. Nagatani, M. Kawai, T. Uto, K. Nanpo, and S. Demura
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Neurology. Diseases of the nervous system ,RC346-429 - Published
- 2024
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4. CLASSIFICATION OF STRAWBERRY FRUIT SHAPE BY MACHINE LEARNING
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T. Ishikawa, A. Hayashi, S. Nagamatsu, Y. Kyutoku, I. Dan, T. Wada, K. Oku, Y. Saeki, T. Uto, T. Tanabata, S. Isobe, and N. Kochi
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Technology ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Applied optics. Photonics ,TA1501-1820 - Abstract
Shape is one of the most important traits of agricultural products due to its relationships with the quality, quantity, and value of the products. For strawberries, the nine types of fruit shape were defined and classified by humans based on the sampler patterns of the nine types. In this study, we tested the classification of strawberry shapes by machine learning in order to increase the accuracy of the classification, and we introduce the concept of computerization into this field. Four types of descriptors were extracted from the digital images of strawberries: (1) the Measured Values (MVs) including the length of the contour line, the area, the fruit length and width, and the fruit width/length ratio; (2) the Ellipse Similarity Index (ESI); (3) Elliptic Fourier Descriptors (EFDs), and (4) Chain Code Subtraction (CCS). We used these descriptors for the classification test along with the random forest approach, and eight of the nine shape types were classified with combinations of MVs + CCS + EFDs. CCS is a descriptor that adds human knowledge to the chain codes, and it showed higher robustness in classification than the other descriptors. Our results suggest machine learning's high ability to classify fruit shapes accurately. We will attempt to increase the classification accuracy and apply the machine learning methods to other plant species.
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- 2018
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5. Performance Test of 20-Stacked Two-Tapes-Bundled REBCO Pancake Coils for Upgrading of 25-T Cryogen-Free Superconducting Magnet to 30 T
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K. Takahashi, A. Badel, A. Zampa, T. Okada, S. Awaji, G. Nishijima, T. Uto, H. Takewa, S. Hanai, S. Ioka, and J. Inagaki
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Electrical and Electronic Engineering ,Condensed Matter Physics ,Electronic, Optical and Magnetic Materials - Published
- 2023
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6. First Validation of Robust REBCO Insert Concept on a Large 20-Pancake Prototype Reaching Up to 25 T
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A. Badel, K. Takahashi, A. Zampa, T. Okada, G. Nishijima, T. Uto, H. Takewa, S. Hanai, S. Ioka, J. Inagaki, and S. Awaji
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Electrical and Electronic Engineering ,Condensed Matter Physics ,Electronic, Optical and Magnetic Materials - Published
- 2023
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7. Electronic structure, Mechanical and Thermodynamic properties of CoYSb (Y= Cr, Mo, W) half-Heusler compounds as potential spintronic materials
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Gboyega A. Adebayo, Stephane Kenmoe, J. O. Akinlami, and O. T. Uto
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Condensed Matter::Materials Science ,Materials science ,Condensed matter physics ,Spintronics ,Electronic structure - Abstract
The CoYSb (Y = Cr, Mo and W) compounds which are XYZ type half-Heusler alloys and also exist in the face centred cubic MgAgAs-type struc-ture conform to F ̄43m space group. In the present work, these compoundsare investigated in different atomic arrangements called, Type-I, Type-II andType-III phases, using Generalized Gradient Approximation (GGA) in the Density Functional Theory (DFT) implemented in QE (Quantum EspressoAb-Initio Simulation Package). The ferromagnetic state of these alloys is studied after investigating their stable structural phase. The calculated electronic band structure and the total electronic density of states indicated nearly half-metallic behaviour in CoMoSb with a possibility of being used in spintronic application, metallic in CoWSb and half-metallic in CoCrSb, with the minority spin band gap of 0.81 eV. Furthermore, the calculated mechanical properties predicted an anisotropic behaviour of these alloys in the stable phase. Finally, due to its high Debye temperature value, CoCrSb possesses a stronger covalent bond than CoMoSb and CoWSb, respectively.
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- 2021
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8. First-Principles Calculations of the Phonon, Mechanical and Thermoelectric Properties of Half-Heusler Alloy VIrSi Alloys
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Paul O. Adebambo, Bamidele I. Adetunji, Oghenekevwe T. Uto, Stephane Kenmoe, and Gboyega A. Adebayo
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Inorganic Chemistry ,General Chemical Engineering ,ddc:540 ,phonon dispersion ,PDOS ,mechanical properties ,power factor ,figure of merit ,Chemie ,General Materials Science ,phonon dispersion -- PDOS -- mechanical properties -- power factor -- figure of merit ,condensed_matter_physics ,Condensed Matter Physics ,Fakultät für Chemie » Theoretische Chemie - Abstract
The density functional theory was used to explore the structural, electronic, dynamical, and thermoelectric properties of a VIrSi Half-Heulser (HH) alloy. The minimum lattice constant of 5.69 ( ̊A) was obtained for VIrSi alloy. Besides, the band structure and the projected density of states for this HH alloy were calculated, and the gap between the valence and conduction bands was noted to be 0.2 eV. Also, the quasi-harmonic approximation was used to predict the dynamical stability of the VIrSi HH alloy. At 300 K, the Seebeck Coefficient of 370 and -270 μV.K−1., respectively, was achieved for the p and n-type doping. From the power factor result, the highest peak of 18 X 1011W/cm.K2 is obtained in the n-type doping. The Figure of Merit (ZT) result revealed that VIrSi alloy possesses a high ZT at room temperature, which would make VIrSi alloy applicable for thermoelectric performance.
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- 2022
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9. Identification of neuropeptides in gastropod mollusks. - Classical and brand-new approaches –
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Kazuyoshi Ukena, Fumihiro Morishita, Toshihiro Horiguchi, M. Furumitsu, T. Watanabe, T. Uto, and Toshio Takahashi
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Identification (biology) ,Computational biology ,Biology - Abstract
For the understanding of the neural regulation of homeostasis, reproduction and behaviors, elucidation of structure and function of neuropeptides is inevitable. A classical technique for peptide purification is the separation of peptidic extract from nervous tissue by the high-performance liquid chromatography, which was followed by screening of fractions with biological or immunological assays. Although this approach requires relatively large amount of tissues for extraction and the screening is time- consuming, we have identified more than 15 kinds of bioactive neuropeptides in the nervous tissue of a marine snail, Thais clavigera. The purified peptides include TEP (Thais excitatory peptide)-1/-2, FRFamide, WWamide and others. The molecular cloning of precursor for each neuropeptide demonstrated that structurally related peptides are aligned in tandem on most of the precursor proteins. To identify the peptides on the precursors, we conducted the de novo sequencing of peptides with the nanoLC-Orbitrap-MS/MS analysis. It identified most of the neuropeptides found on the precursor proteins in the extract from 50 of Thais ganglia. Thus, this technique is suitable for the comprehensive identification of peptides from relatively small amount of tissues. However, several peptides that had been identified by the classical technique, such as APGWamide and leucokinin, were not identified, suggesting the limitation of this brand-new technique.
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- 2020
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10. Hydrothermal system beneath Mt. Fuji volcano inferred from magnetotellurics and electric self-potential
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T. Uto, Wataru Kanda, Tsutomu Ogawa, Yasuo Ogawa, Y. Furukawa, Takeshi Hashimoto, Kenichi Yamazaki, Naoto Oshiman, A. W. Hurst, Makoto Uyeshima, Ryokei Yoshimura, Koki Aizawa, Sabri Bülent Tank, Shin'ya Sakanaka, and Ichiro Shiozaki
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Convection ,geography ,geography.geographical_feature_category ,Hydrothermal circulation ,Conductor ,Geophysics ,Volcano ,Impact crater ,Space and Planetary Science ,Geochemistry and Petrology ,Electrical resistivity and conductivity ,Magnetotellurics ,Earth and Planetary Sciences (miscellaneous) ,Electric current ,Petrology ,Seismology ,Geology - Abstract
Wideband magnetotelluric (MT) soundings were carried out on Mt. Fuji volcano along a northeast to southwest axis. It was found by two-dimensional inversion using the highest quality data (in the frequency range 1–300 Hz) that a good conductor (resistivity of approximately a few ohm m) was located beneath the summit with a lateral extent of approximately 4 km. It begins approximately 1 km below the ground surface; however, its depth cannot be resolved. In our previous study, an intense positive self-potential (SP) anomaly (approximately 2000 mV), was found around a summit crater having a diameter of approximately 3 km. We interpreted the presence of the good conductor and positive SP anomaly as a strong indication of an active hydrothermal system. Subsequently, we searched for conduction current sources to explain the SP distribution on the surface by using the resistivity structure determined by the MT inversion. The results obtained were that a positive conduction current source of the order of 1000 A should be located at the top of the conductor. From these results, we deduced that the conductor represents a hydrothermal system in which single-phase (liquid) convection is taking place. Since the resistivity at a distance from the good conductor can be explained by the effect of cold groundwater, the hydrothermal system does not seem to extend throughout the entire body of the volcano, but seems to be confined to the area beneath the summit crater. Finally, an estimate of the order of magnitude of the subsurface hydrothermal flow was performed using a relation between the fluid volume flux and electric current
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- 2005
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11. Magnetotelluric transect across the Niigata-Kobe Tectonic Zone, central Japan: A clear correlation between strain accumulation and resistivity structure
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Makoto Uyeshima, Shigeru Koyama, Y. Wada, Hiroaki Toh, Yasuo Ogawa, Tadashi Nishitani, Ryokei Yoshimura, Setsuro Nakao, H. Kanezaki, Satoru Yamaguchi, Y. Mochido, Tada-nori Goto, Shin'ya Sakanaka, Takafumi Kasaya, Yasuyoshi Fujita, Yusuke Yamaya, Naoto Oshiman, Koki Aizawa, M. Harada, Masaaki Mishina, T. Uto, Hisao Satoh, Ichiro Shiozaki, Yoshimori Honkura, T. Mogi, and Hideki Murakami
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geography ,geography.geographical_feature_category ,Deformation (mechanics) ,Crust ,Active fault ,Fault (geology) ,Conductor ,Tectonics ,Geophysics ,Magnetotellurics ,General Earth and Planetary Sciences ,Electrical conductor ,Seismology ,Geology - Abstract
[1] We obtained an electrical transect image of the Niigata-Kobe Tectonic Zone (NKTZ). Several major active faults are located in this zone of concentrated deformation. The main features of the final two-dimensional model are a thick resistive block in the upper crust, with a thinned-out portion beneath the Atotsugawa Fault, and a strong conductor in the lower crust that intrudes upward into the upper resistor. The upper crustal resistive zone corresponds well to the spatiality of the NKTZ, and relatively conductive zones sandwiching this resistor may contribute to observed changes in displacement rates. The overlapping locations of the conductor and the low-velocity body in the lower crust indicate that the conductor represents a zone that was weakened by fluids. Given that microearthquakes are localized in the regions between the resistive and conductive zones, we suggest that the distribution of earthquakes is influenced by intrusions of fluid derived from the conductor.
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- 2009
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12. MR Imaging of the Liver before and after Transcatheter Hepatic Chemo-Embolization for Hepatocellular Carcinoma
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K. Miyakoshi, Fujii K, Osamu Ishida, Arita S, Ono Y, Hamada T, Hiroyasu Yoshioka, Kazuhiko Nakagawa, Kawakami A, Mabuchi N, T. Uto, and Shindou H
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medicine.medical_specialty ,Radiological and Ultrasound Technology ,medicine.diagnostic_test ,business.industry ,medicine.medical_treatment ,Granulation tissue ,General Medicine ,medicine.disease ,030218 nuclear medicine & medical imaging ,Intensity (physics) ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Coagulative necrosis ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Angiography ,medicine ,Necrotic Process ,Radiology, Nuclear Medicine and imaging ,Tumor necrosis factor alpha ,Embolization ,Radiology ,business - Abstract
Transcatheter chemo-embolization (TCE) in hepatocellular carcinoma (HCC) was performed in 38 patients. The patients were examined by MR imaging before TCE as well as one week and 4 to 5 weeks after TCE. The tumor signal intensity in T2 weighted images increased in 13 cases and decreased in 19 cases after TCE. Increased intensity seemed to reflect intra-tumoral hemorrhage or liquefaction accompanying tumor necrosis. Decreased intensity seemed to reflect coagulation necrosis. In 9 of 18 cases followed over a 2-month period the signal intensity had decreased in both T1 and T2 weighted images. In these patients the tumor showed no recurrence at angiography and the decreased signal seemed to reflect the completion of coagulation necrosis. A hyper- and/or hypointense rim around the tumor appeared in 22 cases. These changes were thought to be perifocal edema or granulation tissue around the tumor. MR imaging was useful in evaluating the necrotic process of the tumor after TCE.
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- 1990
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13. Nonsteroidal anti-inflammatory drugs enhance allergic reactions in a patient with wheat-induced anaphylaxis
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T. Matsui, T. Uto, Toshihiro Shirai, H. Nakamura, and K. Chida
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Male ,Allergy ,Immunology ,Wheat Hypersensitivity ,Pharmacology ,medicine.disease_cause ,Histamine Release ,chemistry.chemical_compound ,Allergen ,Elimination diet ,Immunology and Allergy ,Medicine ,Humans ,Anaphylaxis ,chemistry.chemical_classification ,Angioedema ,business.industry ,Anti-Inflammatory Agents, Non-Steroidal ,Diclofenac Sodium ,Middle Aged ,medicine.disease ,Gluten ,chemistry ,medicine.symptom ,business ,Histamine - Abstract
Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to enhance the symptoms of food-dependent exercise-induced anaphylaxis (1, 2). We report a rare case of wheat-induced anaphylaxis not related to exercise in which oral challenges with wheat and gluten-induced whole blood histamine release were enhanced by NSAIDs. A 59-year-old man was admitted to our hospital for investigation of recurrent food-induced anaphylaxis. He first developed urticaria after eating noodles at age 58. Since then he frequently had urticaria andoccasionally experienced anaphylaxis, including dyspnoea, wheezing, angioedema, and loss of consciousness after ingesting wheat, including noodles, bread, breaded cutlets, and tempura (Japanese deep-fried foods). It was determined that he had these episodes of anaphylaxis without exercise. Total IgE was 160 IU/ml. Skin-prick testing and specific IgEwere positive for wheat and gluten, the major allergen in wheat-induced allergy. To determine an elimination diet and to instruct the patient, open oral challenges were performed. Oral challenges with bread, noodles, cutlets, and tempura were all negative. However, when 30 mg of diclofenac sodium, an NSAID, was taken just before the challenge, he developed urticaria 1 h after eating noodles or tempura.He developed no symptoms after taking diclofenac sodium only. To clarify the effect of NSAIDs on wheat-induced anaphylaxis, we measured histamine release after in vitro exposure to gluten with or without tolmetin sodium, an NSAID, in this patient and a normal control subject. Heparinized whole blood samples were taken and incubated with gluten at concentrations ranging from 2.5 to 2500 lg/ml and with tolmetin sodium at concentrations ranging from 0.125 to 12.5 mg/ml for 30 min at 37 C. After centrifugation, histamine was measured in the cell-free supernatants by radioimmunoassay. Histamine release was found to be positive with gluten at the concentration of 2500 lg/ml in the patient. With tolmetin sodium at concentrations of 0.125 and 1.25 mg/ml, gluten-induced histamine release was not affected. However, tolmetin sodium at the concentration of 12.5 mg/ml enhanced the gluten-induced histamine release at all concentraions of gluten. Interestingly, tolmetin sodium enhanced histamine release even in the absence of gluten in the control subject as well as in the patient. Histamine release was not found in other conditions in the control subject. At follow-up 1 year after the discharge, he remained asymptomatic after strict elimination of wheat. The results of our in vitro study indicate that the induction of positive oral challenges with wheat after pretreatment with an NSAID is, at least partly, because of enhancement of histamine release. To our knowledge, this is the first report of wheatinduced anaphylaxis not related to exercise confirming thatNSAIDs enhance type I allergic reactions. Previous studies demonstrated that NSAIDs enhance in vitro histamine release induced by IgEor nonIgE-mediated mechanisms (3). In our study, histamine release was induced by tolmetin sodium even in the absence of allergen. In this regard, we speculate that the extent of enhancement of histamine releasemaydependon the type anddose of the NSAIDs as our patient developed no symptoms after taking diclofenac sodium only. We found that enhancement of the allergic symptoms induced by NSAIDs is not a specific phenomenon in fooddependent exercise-induced anaphylaxis, but can occur in other type I allergic diseases. Furthermore, pretreatment with NSAIDs under controlled conditions is useful for confirming the diagnosis of food-induced allergy when food challenge tests fail to induce positive reactions.
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- 2003
14. [Congenital myasthenic syndrome caused by presynaptic defects]
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T, Uto and Y, Sonoda
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Diagnosis, Differential ,Myasthenic Syndromes, Congenital ,Humans ,Cholinesterase Inhibitors ,Synaptic Vesicles ,Prognosis ,Acetylcholine - Published
- 2001
15. PRIMARY DEMYELINATION OF THE SPINAL CORD AND ADULT T-CELL LEUKEMIA (ATL): AN AUTOPSY CASE OF ACUTE TRANSVERSE MYELOPATHY WITH ATL INVASION
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T. Uto, Hidetoshi Fukunaga, J. Wakimoto, Mitsuhiro Osame, S. Izumo, Takashi Moritoyo, Takefumi Kasai, Moe Moe Aye, and H. Yoshidome
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Pathology ,medicine.medical_specialty ,Primary demyelination ,business.industry ,Immunology ,T-cell leukemia ,Autopsy case ,Spinal cord ,medicine.anatomical_structure ,Virology ,medicine ,Immunology and Allergy ,business ,Acute transverse myelopathy - Published
- 1999
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16. Estimation of scattered radiation from added filter
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K. Usami, T. Uto, T. Mizutani, and Kouji Yamada
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Computer science ,Filter (video) ,Acoustics ,General Medicine ,Radiation - Published
- 1996
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17. Dose estimation of cardiac radio-diagnosis using NDD
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T. Mizutani, T. Uto, Kouji Yamada, and K. Usami
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business.industry ,Dose estimation ,Medicine ,General Medicine ,Nuclear medicine ,business - Published
- 1996
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18. An attempt of 3-D coordinates indication in bi-plane cine angiography 3rd report : Study of X-P angles
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Hiroharu Nakamura, T. Okiguchi, Masayuki Nishiki, Satoru Oishi, Chiharu Tanabe, Hiroshi Asahina, Kunihiro Yasunaga, Yoshihiko Murano, and T. Uto
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Physics ,medicine.diagnostic_test ,Plane (geometry) ,Report study ,business.industry ,Angiography ,medicine ,General Medicine ,Nuclear medicine ,business - Published
- 1996
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19. 148. The relation of input-phosphor thickness to contrast in a CsI Image intensifier
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M. Uemura, Kouji Yamada, T. Mizutani, and T. Uto
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Optics ,Materials science ,business.industry ,law ,media_common.quotation_subject ,Contrast (vision) ,Image intensifier ,Phosphor ,General Medicine ,business ,media_common ,law.invention - Published
- 1993
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20. On the effect of chemical control of rice bacterial leaf blight, caused by Xanthomonas oryzae
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J. Nishimura and T. Uto
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Horticulture ,Xanthomonas oryzae ,Blight ,General Medicine ,Biology ,Chemical control ,biology.organism_classification - Published
- 1967
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21. Identification of neuropeptides in gastropod mollusks. - Classical and brand-new approaches –.
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F Morishita, T Takahashi, T Watanabe, T Uto, K Ukena, M Furumitsu, and T Horiguchi
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- 2020
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22. Effect of Hepatic Lipid Overload on Accelerated Hepatocyte Proliferation Promoted by HGF Expression via the SphK1/S1PR2 Pathway in MCD-diet Mouse Partial Hepatectomy.
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Lkham-Erdene B, Choijookhuu N, Kubota T, Uto T, Mitoma S, Shirouzu S, Ishizuka T, Kai K, Higuchi K, Mo Aung K, Batmunkh JE, Sato K, and Hishikawa Y
- Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is becoming a major health problem worldwide. Liver regeneration is crucial for restoring liver function, and is regulated by extraordinary complex process, involving numerous factors under both physiologic and pathologic conditions. Sphingosine-1-phosphate (S1P), a bioactive sphingolipid synthesized by sphingosine kinase 1 (SphK1), plays an important role in liver function through S1P receptors (S1PRs)-expressing cells. In this study, we investigated the effect of lipid overload on hepatocyte proliferation in a mouse hepatic steatosis model induced by feeding a methionine- and choline-deficient (MCD) diet. After 50% partial hepatectomy (PHx), liver tissues were sampled at various timepoints and then analyzed by immunohistochemistry, oil Red-O staining, quantitative-polymerase chain reaction (qPCR), and flow cytometry. In mice fed the MCD-diet, significantly exacerbated hepatic steatosis and accelerated liver regeneration were observed. After PHx, hepatocyte proliferation peaked at 48 and 36 hr in the liver of chow- and MCD-diet fed mice, respectively. By contrast, increased expression of S1PR2 was observed in hepatic neutrophils and macrophages of MCD-diet fed mice. Flow cytometry and qPCR experiments demonstrated that levels of HGF and FGF2 released by neutrophils and macrophages were significantly higher in MCD-diet fed mice. In conclusion, hepatic lipid overload recruits Kupffer cells and neutrophils that release HGF and FGF2 via SphK1/S1PR2 activation to accelerate hepatocyte proliferation., Competing Interests: VWe have no conflict of interest to declare., (2024 The Japan Society of Histochemistry and Cytochemistry.)
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- 2024
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23. Crucial role of dendritic cells in the generation of anti-tumor T-cell responses and immunogenic tumor microenvironment to suppress tumor development.
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Tominaga M, Uto T, Fukaya T, Mitoma S, Riethmacher D, Umekita K, Yamashita Y, and Sato K
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- Animals, Mice, T-Lymphocytes immunology, Myeloid-Derived Suppressor Cells immunology, Myeloid-Derived Suppressor Cells metabolism, Mice, Inbred C57BL, CD11c Antigen metabolism, Neoplasms immunology, Cell Line, Tumor, Dendritic Cells immunology, Tumor Microenvironment immunology, Mice, Transgenic
- Abstract
Dendritic cells (DCs) are known as unique professional antigen (Ag)-presenting cells (APCs) to prime naïve T cells for the initiation of adaptive immunity. While DCs are believed to play a pivotal role in generating anti-tumor T-cell responses, the importance of DCs in the protection from the progression of tumors remains elusive. Here, we show how the constitutive deficiency of CD11c
hi DCs influences the progression of tumors with the use of binary transgenic mice with constitutive loss of CD11chi DCs. Constitutive loss of CD11chi DCs not only enhances the progression of tumors but also reduces the responses of Ag-specific T cells. Furthermore, the congenital deficiency of CD11chi DCs generates the immunosuppressive tumor microenvironment (TME) that correlates with the marked accumulation of myeloid-derived suppressor cells (MDSCs) and the prominent productions of immunosuppressive mediators. Thus, our findings suggest that CD11chi DCs are crucial for generating anti-tumor T-cell responses and immunogenic TME to suppress the development of tumors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tominaga, Uto, Fukaya, Mitoma, Riethmacher, Umekita, Yamashita and Sato.)- Published
- 2024
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24. Fisetin is a selective adenosine triphosphate-competitive inhibitor for mitogen-activated protein kinase kinase 4 to inhibit lipopolysaccharide-stimulated inflammation.
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He Z, Uto T, Tanigawa S, Sakao K, Kumamoto T, Xie K, Pan X, Wu S, Yang Y, Komatsu M, and Hou DX
- Abstract
The mitogen-activated protein kinase kinase 4 (MKK4), a member of the MAP kinase kinase family, directly phosphorylates and activates the c-Jun NH2-terminal kinases (JNK), in response to proinflammatory cytokines and cellular stresses. Regulation of the MKK4 activity is considered to be a novel approach for the prevention and treatment of inflammation. The aim of this study was to identify whether fisetin, a potential anti-inflammatory compound, targets MKK4-JNK cascade to inhibit lipopolysaccharide (LPS)-stimulated inflammatory response. RAW264 macrophage pretreated with fisetin following LPS stimulation was used as a cell model to investigate the transactivation and expression of related-inflammatory genes by transient transfection assay, electrophoretic mobility shift assay (EMSA), or enzyme-linked immunosorbent assay (ELISA), and cellular signaling as well as binding of related-signal proteins by Western blot, pull-down assay and kinase assay, and molecular modeling. The transactivation and expression of cyclooxygenase-2 (COX-2) gene as well as prostaglandin E
2 (PGE2 ) secretion induced by LPS were inhibited by fisetin in a dose-dependent manner. Signaling transduction analysis demonstrated that fisetin selectively inhibited MKK4-JNK1/2 signaling to suppress the phosphorylation of transcription factor AP-1 without affecting the NF-κB and Jak2-Stat3 signaling as well as the phosphorylation of Src, Syk, and TAK1. Furthermore, in vitro and ex vivo pull-down assay using cell lysate or purified protein demonstrated that fisetin could bind directly to MKK4. Molecular modeling using the Molecular Operating Environment™ software indicated that fisetin docked into the ATP-binding pocket of MKK4 with a binding energy of -71.75 kcal/mol and formed a 1.70 Å hydrogen bound with Asp247 residue of MKK4. The IC50 of fisetin against MKK4 was estimated as 2.899 μM in the kinase assay, and the ATP-competitive effect was confirmed by ATP titration. Taken together, our data revealed that fisetin is a potent selective ATP-competitive MKK4 inhibitor to suppress MKK4-JNK1/2-AP-1 cascade for inhibiting LPS-induced inflammation., (© 2024 The Author(s). BioFactors published by Wiley Periodicals LLC on behalf of International Union of Biochemistry and Molecular Biology.)- Published
- 2024
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25. Application of Monoclonal Antibodies against Naturally Occurring Bioactive Ingredients.
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Fujii S, Uto T, Hayashi H, Putalun W, Sakamoto S, Tanaka H, and Shoyama Y
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Monoclonal antibodies (Mabs) are widely used in a variety of fields, including protein identification, life sciences, medicine, and natural product chemistry. This review focuses on Mabs against naturally occurring active compounds. The preparation of Mabs against various active compounds began in the 1980s, and now there are fewer than 50 types. Eastern blotting, which was developed as an antibody staining method for low-molecular-weight compounds, is useful for its ability to visually represent specific components. In this method, a mixture of lower-molecular-weight compounds, particularly glycosides, are separated by thin-layer chromatography (TLC). The compounds are then transferred to a membrane by heating, followed by treatment with potassium periodate (KIO
4 ) to open the sugar moiety of the glycoside on the membrane to form an aldehyde group. Proteins are then added to form Schiff base bonds to enable adsorption on the membrane. A Mab is bound to the glycoside moiety on the membrane and reacts with a secondary antibody to produce color. Double Eastern blotting, which enables the simultaneous coloration of two glycosides, can be used to evaluate quality and estimate pharmacological effects. An example of staining by Eastern blotting and a component search based on the results will also be presented. A Mab-associated affinity column is a method for isolating antigen molecules in a single step. However, the usefulness of the wash fractions that are not bound to the affinity column is unknown. Therefore, we designated the wash fraction the "knockout extract". Comparing the nitric oxide (NO) production of a glycyrrhizin (GL)-knockout extract of licorice with a licorice extract revealed that the licorice extract is stronger. Therefore, the addition of GL to the GL-knockout extract of licorice increased NO production. This indicates that GL has synergic activity with the knockout extract. The GL-knockout extract of licorice inhibited high-glucose-induced epithelial-mesenchymal transition in NRK-52E cells, primarily by suppressing the Notch2 pathway. The real active constituent in licorice may be constituents other than GL, which is the causative agent of pseudohyperaldosteronism. This suggests that a GL-knockout extract of licorice may be useful for the treatment of diabetic nephritis.- Published
- 2024
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26. Optimization of Zwitterionic Polymers for Cell Cryopreservation.
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Kato Y, Uto T, Ishizaki T, Tanaka D, Ishibashi K, Matsuda Y, Onoda I, Kobayashi A, Hazawa M, Wong RW, Takahashi K, Hirata E, and Kuroda K
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- Animals, Humans, Cell Survival drug effects, Freezing, Mice, Cryopreservation methods, Polymers chemistry, Polymers pharmacology, Cryoprotective Agents pharmacology, Cryoprotective Agents chemistry, Cell Proliferation drug effects
- Abstract
Cryopreservation techniques are valuable for the preservation of genetic properties in cells, and the development of this technology contributes to various fields. In a previous study, an isotonic freezing medium composed of poly(zwitterion) (polyZI) has been reported, which alleviates osmotic shock, unlike typical hypertonic freezing media. In this study, the primitive freezing medium composed of emerging polyZI is optimized. Imidazolium/carboxylate-type polyZI (VimC
3 C) is the optimal chemical structure. The molecular weight and degree of ion substitution (DSion ) are not significant factors. There is an impediment with the primitive polyZI freezing media. While the polyZI forms a matrix around the cell membrane to protect cells, the matrix is difficult to remove after thawing, resulting in low cell proliferation. Unexpectedly, increasing the poly(VimC3 C) concentration from 10% to 20% (w/v) improves cell proliferation. The optimized freezing medium, 20% (w/v) poly(VimC3 C)_DSion(100%) /1% (w/v) NaCl aqueous solution, exhibited a better cryoprotective effect., (© 2024 Wiley‐VCH GmbH.)- Published
- 2024
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27. Surgical Treatment for Emphysematous Osteomyelitis of the Lumbar Spine: A Case Report.
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Nagatani S, Kato S, Yokogawa N, Shimizu T, Kawai M, Uto T, Ishino Y, Nanpo K, and Demura S
- Abstract
Competing Interests: Conflicts of Interest: The authors declare that there are no relevant conflicts of interest.
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- 2024
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28. Interaction-Induced ac Stark Shift of Exciton-Polaron Resonances.
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Uto T, Evrard B, Watanabe K, Taniguchi T, Kroner M, and İmamoğlu A
- Abstract
Laser-induced shift of atomic states due to the ac Stark effect has played a central role in cold-atom physics and facilitated their emergence as analog quantum simulators. Here, we explore this phenomenon in an atomically thin layer of semiconductor MoSe_{2}, which we embedded in a heterostructure enabling charge tunability. Shining an intense pump laser with a small detuning from the material resonances, we generate a large population of virtual collective excitations and achieve a regime where interactions with this background population are the leading contribution to the ac Stark shift. Using this technique we study how itinerant charges modify-and dramatically enhance-the interactions between optical excitations. In particular, our experiments show that the interaction between attractive polarons could be more than an order of magnitude stronger than those between bare excitons.
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- 2024
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29. Protein Cryoprotectant Ability of the Aqueous Zwitterionic Solution.
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Takekiyo T, Yamada S, Uto T, Nakayama M, Hirata T, Ishizaki T, Kuroda K, and Yoshimura Y
- Subjects
- Freezing, Water chemistry, Dimethyl Sulfoxide, Solvents, Proteins, Cryoprotective Agents chemistry, Cryopreservation methods
- Abstract
Protein cryopreservation is important for the long-term storage of unstable proteins. Recently, we found that N -acetylglucosaminyltransferase-V (GnT-V) can be cryopreserved in a deep freezer without temperature control using a dilute binary aqueous solution of 3-(1-(2-(2-methoxyethoxy)ethyl)imidazol-3-io)butane-1-carboxylate (OE
2 imC3 C) [10 wt %, mole fraction of solute ( x ) = 7.75 × 10-3 ], an artificial zwitterion. However, it is unclear which solvent properties are required in these media to preserve unstable proteins, such as GnT-V. In this study, we investigated the melting phenomena and solution structure of dilute binary aqueous OE2 imC3 C solutions [ x = 0-2.96 × 10-2 (0-30 wt %)] using differential scanning calorimetry (DSC) and Raman and Fourier transform infrared (FTIR) spectroscopies combined with molecular dynamics (MD) simulation to compare the cryoprotectant ability of OE2 imC3 C with two general cryoprotectants (CPAs), glycerol and dimethyl sulfoxide. DSC results indicated that aqueous OE2 imC3 C solutions can be melted at lower temperatures with less energy than the control CPA solution, with increasing x , primarily due to OE2 imC3 C having a higher content of unfrozen water molecules. Moreover, Raman and FTIR results showed that the high content of unfrozen water molecules in aqueous OE2 imC3 C solutions was due to the hydration around the ionic parts (the COO- group and imidazolium ring) and the OCH2 CH2 O segment. In addition, the MD simulation results showed that there were fewer structured water molecules around the OCH2 CH2 O segment than the hydration water molecules around the ionic parts. These solvent properties suggest that dilute aqueous OE2 imC3 C solutions are effective in preventing freezing, even in a deep freezer. Therefore, this medium has the potential to act as a novel cryoprotectant for proteins in biotechnology and biomedical fields.- Published
- 2024
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30. Highly sensitive indirect competitive enzyme-linked immunosorbent assay based on a monoclonal antibody against saikosaponin b2 for quality control of Kampo medicines containing Bupleuri radix.
- Author
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Ochi A, Fujii S, Ohta T, Uto T, Nuntawong P, Tanaka H, Morimoto S, and Sakamoto S
- Subjects
- Antibodies, Monoclonal, Medicine, Kampo, Reproducibility of Results, Quality Control, Enzyme-Linked Immunosorbent Assay, Saponins analysis, Oleanolic Acid
- Abstract
Saikosaponins are naturally occurring oleanane-type triterpenoids that are found in Bupleuri radix (root of Bupleurum falcatum) and exhibit a broad biological activity spectrum. Saikosaponin b2 (SSb2) is the main saikosaponin in Kampo medicine extracts and is a designated quality control marker for the same in the Japanese Pharmacopeia. Although some monoclonal antibodies (mAbs) against saikosaponins have been produced to evaluate the quality of Bupleuri radix and related products, anti-SSb2 mAbs have not been used to quantify SSb2 in Kampo medicines. To address this knowledge gap, we herein established a new hybridoma cell line secreting a highly specific anti-SSb2 mAb and developed an indirect competitive enzyme-linked immunosorbent assay (icELISA) based on this mAb for the detection of SSb2 in Bupleuri radix-containing Kampo medicines. The generated SSb2-recognized mAb exhibited high specificity to SSb2 in icELISA. The developed assay featured high sensitivity (linearity range = 1.95-125 ng/ml), accuracy, precision and reproducibility (coefficient of variation < 5%), and the thus determined SSb2 contents were strongly correlated with those obtained using liquid chromatograph-mass spectrometer. These results suggest that the anti-SSb2 mAb-based icELISA method can be used for the quality control and standardization of Kampo medicines containing Bupleuri radix., (© 2023. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)
- Published
- 2024
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31. Upregulation of brain-derived neurotrophic factor by Shiikuwasha (Citrus depressa Hayata).
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Nakajima K, Okubo S, Ohta T, Uto T, and Oiso S
- Abstract
Background: A reduction in the brain-derived neurotrophic factor (BDNF) level in the brain causes depression, whereas an increase in its level has therapeutic benefits against depression. BDNF is synthesized in various peripheral tissues and transported to the brain via the peripheral circulation across the blood-brain barrier. Therefore, substances that upregulate peripheral BDNF level may be used to prevent and treat depression. Previously, we demonstrated that Citrus unshiu peel (Chinpi) and C. natsudaidai increased BDNF level in a human renal adenocarcinoma cell line ACHN, which has BDNF-producing ability. Here, we evaluated whether Shiikuwasha (C. depressa Hayata), a citrus species cultivated in East Asia, can upregulate BDNF level in ACHN cells., Methods: We evaluated the effects of test samples on BDNF production by measuring BDNF level in the medium of ACHN cells after a 24 h cultivation in the presence of test samples. The BDNF mRNA level was measured by quantitative reverse transcription-polymerase chain reaction, and the phosphorylation level of cyclic adenosine monophosphate response element-binding protein (CREB), a transcription factor regulating BDNF expression, was determined using Western blotting., Results: We found that methanol extracts of Shiikuwasha peel, pulp, and seed increased the BDNF level in the culture medium of ACHN cells. Shiikuwasha peel and pulp extracts also upregulated BDNF mRNA level and phosphorylation of CREB., Conclusions: These results suggest that Shiikuwasha includes the candidate antidepressant substances with peripheral BDNF-upregulation effect., (© 2023. The Author(s).)
- Published
- 2023
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32. Cell-compatible isotonic freezing media enabled by thermo-responsive osmolyte-adsorption/exclusion polymer matrices.
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Kato Y, Matsuda Y, Uto T, Tanaka D, Ishibashi K, Ishizaki T, Ohta A, Kobayashi A, Hazawa M, Wong RW, Ninomiya K, Takahashi K, Hirata E, and Kuroda K
- Abstract
During the long-term storage of cells, it is necessary to inhibit ice crystal formation by adding cryoprotectants. Non-cell-permeable cryoprotectants have high osmotic pressure which dehydrates cells, indirectly suppressing intracellular ice crystal formation. However, the high osmotic pressure and dehydration often damage cells. Emerging polymer-type non-cell-permeable cryoprotectants form matrices surrounding cells. These matrices inhibit the influx of extracellular ice nuclei that trigger intracellular ice crystal formation. However, these polymer-type cryoprotectants also require high osmotic pressure to exert an effective cryoprotecting effect. In this study, we designed a poly(zwitterion) (polyZI) that forms firm matrices around cells based on their high affinity to cell membranes. The polyZI successfully cryopreserved freeze-vulnerable cells under isotonic conditions. These matrices also controlled osmotic pressure by adsorbing and desorbing NaCl depending on the temperature, which is a suitable feature for isotonic cryopreservation. Although cell proliferation was delayed by the cellular matrices, washing with a sucrose solution improved proliferation., (© 2023. The Author(s).)
- Published
- 2023
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33. Tracheobronchitis and laryngitis associated with Crohn's disease.
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Nakai S, Morikawa M, Hiramatsu T, Murakami Y, Nishimoto K, Matsushima S, Harada M, Uto T, Sato J, Imokawa S, and Suda T
- Abstract
We report a 68-year-old woman with tracheobronchitis and laryngitis associated with Crohn's disease (CD), which was discovered during the evaluation of suspected lung cancer. She had no symptoms induced by these upper airway diseases (UADs). Bronchoscopy revealed swelling of the epiglottis with edematous change and a mass like epiglottis fold. There were nodular and edematous changes in the trachea and bilateral main bronchus. Histological findings demonstrated infiltration by numerous lymphocytes and plasma cells. Dexamethasone as the premedication for chemotherapy against lung cancer was efficacious for these extraintestinal manifestations of CD. Our case was rare in that bronchial lesion and UADs appeared concomitantly., Competing Interests: I declare on behalf of my co-authors and myself that we do not have any conflict of interest to declare., (© 2023 The Authors.)
- Published
- 2023
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34. Clec4A4 Acts as a Negative Immune Checkpoint Regulator to Suppress Antitumor Immunity.
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Uto T, Fukaya T, Mitoma S, Nishikawa Y, Tominaga M, Choijookhuu N, Hishikawa Y, and Sato K
- Abstract
Clec4A4 is a C-type lectin receptor (CLR) exclusively expressed on murine conventional dendritic cells (cDC) to regulate their activation status. However, the functional role of murine Clec4A4 (mClec4A4) in antitumor immunity remains unclear. Here, we show that mClec4A4 serves as a negative immune checkpoint regulator to impair antitumor immune responses. Deficiency of mClec4A4 lead to a reduction in tumor development, accompanied by enhanced antitumor immune responses and amelioration of the immunosuppressive tumor microenvironment (TME) mediated through the enforced activation of cDCs in tumor-bearing mice. Furthermore, antagonistic mAb to human CLEC4A (hCLEC4A), which is the functional orthologue of mClec4A4, exerted protection against established tumors without any apparent signs of immune-related adverse events in hCLEC4A-transgenic mice. Thus, our findings highlight the critical role of mClec4A4 expressed on cDCs as a negative immune checkpoint molecule in the control of tumor progression and provide support for hCLEC4A as a potential target for immune checkpoint blockade in tumor immunotherapy., (©2023 The Authors; Published by the American Association for Cancer Research.)
- Published
- 2023
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35. Cytokine profiling identifies circulating IL-6 and IL-15 as prognostic stratifiers in patients with non-small cell lung cancer receiving anti-PD-1/PD-L1 blockade therapy.
- Author
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Inoue Y, Inui N, Karayama M, Asada K, Fujii M, Matsuura S, Uto T, Hashimoto D, Matsui T, Ikeda M, Yasui H, Hozumi H, Suzuki Y, Furuhashi K, Enomoto N, Fujisawa T, and Suda T
- Subjects
- Humans, Immune Checkpoint Proteins therapeutic use, Prognosis, Male, Female, Aged, Carcinoma, Non-Small-Cell Lung blood, Carcinoma, Non-Small-Cell Lung drug therapy, Nivolumab therapeutic use, Antineoplastic Agents therapeutic use, Interleukin-6 blood, Interleukin-15 blood, Lung Neoplasms blood, Lung Neoplasms drug therapy
- Abstract
Whether circulating levels of specific cytokines at baseline link with treatment efficacy of immune checkpoint blockade (ICB) therapy in patients with non-small cell lung cancer remains unknown. In this study, serum samples were collected in two independent, prospective, multicenter cohorts before the initiation of ICB. Twenty cytokines were quantified, and cutoff values were determined by receiver operating characteristic analyses to predict non-durable benefit. The associations of each dichotomized cytokine status with survival outcomes were assessed. In the discovery cohort (atezolizumab cohort; N = 81), there were significant differences in progression-free survival (PFS) in accordance with the levels of IL-6 (log-rank test, P = 0.0014), IL-15 (P = 0.00011), MCP-1 (P = 0.013), MIP-1β (P = 0.0035), and PDGF-AB/BB (P = 0.016). Of these, levels of IL-6 and IL-15 were also significantly prognostic in the validation cohort (nivolumab cohort, N = 139) for PFS (log-rank test, P = 0.011 for IL-6 and P = 0.00065 for IL-15) and overall survival (OS; P = 3.3E-6 for IL-6 and P = 0.0022 for IL-15). In the merged cohort, IL-6
high and IL-15high were identified as independent unfavorable prognostic factors for PFS and OS. The combined IL-6 and IL-15 status stratified patient survival outcomes into three distinct groups for both PFS and OS. In conclusion, combined assessment of circulating IL-6 and IL-15 levels at baseline provides valuable information to stratify the clinical outcome of patients with non-small cell lung cancer treated with ICB. Further studies are required to decipher the mechanistic basis of this finding., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)- Published
- 2023
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36. Clinical Outcomes of Total En Bloc Spondylectomy for Previously Irradiated Spinal Metastases: A Retrospective Propensity Score-Matched Comparative Study.
- Author
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Yokogawa N, Kato S, Shimizu T, Kurokawa Y, Kobayashi M, Yamada Y, Nagatani S, Kawai M, Uto T, Murakami H, Kawahara N, and Demura S
- Abstract
This study aimed to investigate the clinical outcomes of total en bloc spondylectomy (TES) for spinal metastases previously treated with radiotherapy (RT). This study enrolled 142 patients who were divided into two groups: those with and those without an RT history. Forty-two patients were selected from each group through propensity score matching, and postoperative complications, local recurrence, and overall survival rates were compared. The incidence of postoperative complications was significantly higher in the group with an RT history than in the group without an RT history (57.1% vs. 35.7%, respectively). The group with an RT history had a higher local recurrence rate than the group without an RT history (1-year rate: 17.5% vs. 0%; 2-year rate: 20.8% vs. 2.9%; 5-year rate: 24.4% vs. 6.9%). The overall postoperative survival tended to be lower in the group with an RT history; however, there was no significant difference between the two groups (2-year survival: 64.3% vs. 66.7%; 5-year survival: 47.3% vs. 57.1%). When planning a TES for irradiated spinal metastases, the risk of postoperative complications and local recurrence should be fully considered.
- Published
- 2023
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- View/download PDF
37. Extended Ensemble Molecular Dynamics Study of Ammonia-Cellulose I Complex Crystal Models: Free-Energy Landscape and Atomistic Pictures of Ammonia Diffusion in the Crystalline Phase.
- Author
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Yui T, Uto T, and Noda K
- Subjects
- Cellulose, Diffusion, Water, Molecular Dynamics Simulation, Ammonia chemistry
- Abstract
Here, we report extended ensemble molecular dynamics simulations of ammonia-cellulose I complex crystal models to evaluate the diffusion behavior of the guest ammonia molecules and the potential of mean force (PMF), namely, the free energy change along the chosen reaction coordinate, for migration of an ammonia molecule in the crystal models. Accelerated molecular dynamics simulations confirmed that ammonia molecules almost exclusively diffused through the hydrophilic channel even when the crystal framework was retained. Adaptive steered molecular dynamics simulations detected distinct PMF peaks with heights of approximately 7 kcal/mol as the ammonia molecule passed through the cellulose-chain layers. Introducing hybrid quantum mechanical and molecular mechanics theory to the adaptive steered molecular dynamics simulation effectively lowered the heights of the PMF peaks to approximately 5 kcal/mol, accompanied by a slight decrease in the baseline. Removal of the ammonia molecules in the neighboring channels resulted in a continuous increase in the baseline for the migration of an ammonia molecule in the hydrophilic channel. When the halves of the crystal model were separated to widen the hydrophilic channel to 0.2 nm, the PMF profiles exhibited an unexpected increase. This resulted from water structuring in the expanded hydrophilic channel, which disappeared with further expansion of the hydrophilic channel to 0.3 nm.
- Published
- 2023
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38. Six-week oral prednisolone therapy for immune-related pneumonitis: a single-arm phase II study.
- Author
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Karayama M, Inui N, Inoue Y, Yasui H, Hozumi H, Suzuki Y, Furuhashi K, Fujisawa T, Enomoto N, Asada K, Uto T, Fujii M, Matsui T, Matsuura S, Hashimoto D, Toyoshima M, Ikeda M, Matsuda H, Inami N, Kaida Y, Funayama S, Ichikawa S, Goshima S, and Suda T
- Subjects
- Humans, Prospective Studies, Prednisolone therapeutic use, Recurrence, Pneumonia, Neoplasms drug therapy
- Abstract
Background: There has been no prospective trial for treatment of immune-related pneumonitis (irP) occurred after immune checkpoint inhibitors (ICIs)., Methods: In this single-arm phase II study, patients with cancer with grade ≥2 irP received oral prednisolone (1 mg/kg/day), tapered over 6 weeks. The primary endpoint was a pneumonitis control rate at 6 weeks from the start of the study treatment, defined as complete disappearance or partial improvement of irP in high-resolution CT of the chest., Results: Among 57 patients enrolled, 56 were included in the final analysis. The most frequent cause of irP was single ICI therapy (51.8%), followed by combination with chemotherapy plus ICI (39.3%). Thirty-five (62.5%) patients had grade 2 irP and 21 (37.5%) had grade ≥3. Fifty-one (91.1%) patients completed the study treatment while 5 discontinued the study treatment because of relapse of irP (n=1), death from cancer (n=1), occurrence of immune-related hepatitis (n=1), extension of the treatment duration more than 6 weeks (n=1), and attending physician's decision (n=1). Six weeks after the start of the study treatment, 16 (28.5%) patients demonstrated complete recovery from irP, 35 (62.5%) had a partial improvement in irP, 1 (1.8%) had a relapse of irP, and 4 (7.1%) were not evaluable. The pneumonitis control rate at 6 weeks was 91.1% (95% CI, 80.7% to 96.1%). Twelve weeks after the start of the study treatment, 5 (8.9%), 27 (48.2%), and 15 (26.8%) patients demonstrated complete recovery, partial improvement, and relapse, respectively, and 9 (16.1%) were not evaluable. The pneumonitis control rate at 12 weeks was 57.1% (95% CI, 44.1% to 69.2%). During the observation period, 18 (32.1%) patients experienced a relapse of irP, and of those, 17 received re-treatment with corticosteroids. Grade ≥3 adverse events occurred in 10 (17.9%) patients, in which hyperglycemia was most frequent (n=6). There was no treatment-related death., Conclusions: In this first prospective study for irP, prednisolone at 1 mg/kg/day, tapered over 6 weeks, demonstrated a promising clinical benefit and manageable toxicity, suggesting a potential treatment option for irP., Trial Registration Number: jRCT: 1041190029., Competing Interests: Competing interests: No, there are no competing interests., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2023
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39. Serum immune modulators associated with immune-related toxicities and efficacy of atezolizumab in patients with non-small cell lung cancer.
- Author
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Inoue Y, Inui N, Karayama M, Asada K, Matsuura S, Ikeda M, Uto T, Fujii M, Hashimoto D, Matsui T, Matsuda H, Inami N, Toyoshima M, Kaida Y, Yasui H, Hozumi H, Suzuki Y, Furuhashi K, Enomoto N, Fujisawa T, and Suda T
- Subjects
- Humans, Programmed Cell Death 1 Receptor, Prospective Studies, Immunologic Factors, B7-H1 Antigen, Retrospective Studies, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms
- Abstract
Purpose: Identifying patients at high risk of immune-related adverse events (irAEs) that impede the achievement of durable efficacy of programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) blockade therapy is important in improving their management. Identification of a novel predictive factor of therapeutic benefit is also important in improving patient selection for treatment with PD-1/PD-L1 inhibitors. Further determinants driving response and linking with irAEs are urgently required., Methods: To address these unmet needs in the field, we explored whether 27 soluble checkpoint proteins and immunomodulatory proteins in serum at the therapy baseline and after week 3 were associated with irAE onset and therapeutic efficacy using MILLIPLEX Human Immuno-Oncology Checkpoint Protein Panel assays in a prospective, multicenter cohort of 81 patients with non-small cell lung cancer (NSCLC) receiving atezolizumab monotherapy., Results: By competing-risks regression analysis, we identified that high levels of B cell-activating factor (BAFF) at baseline were a significant and strong risk factor of irAEs (hazard ratio, 5.61; 95% confidence interval, 2.43-12.96; P < 0.0001). We also identified that increased inducible T cell co-stimulator (ICOS) during the first therapeutic cycle was an independent factor associated with prolonged progression-free survival and overall survival., Conclusion: These findings are in keeping with the reported mechanistic basis of these molecules and may provide potential guidance for clinical decision-making to improve patient care. Further validation studies are warranted. Trial registration UMIN000035616 (January 28, 2019)., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2023
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40. The Impact of Frailty on Postoperative Complications in Total En Bloc Spondylectomy for Spinal Tumors.
- Author
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Kawai M, Demura S, Kato S, Yokogawa N, Shimizu T, Kurokawa Y, Kobayashi M, Yamada Y, Nagatani S, Uto T, and Murakami H
- Abstract
Total en bloc spondylectomy (TES) is an effective treatment for spinal tumors. However, its complication rate is high, and the corresponding risk factors remain unclear. This study aimed to clarify the risk factors for postoperative complications after TES, including the patient's general condition, such as frailty and their levels of inflammatory biomarkers. We included 169 patients who underwent TES at our hospital from January 2011-December 2021. The complication group comprised patients who experienced postoperative complications that required additional intensive treatments. We analyzed the relationship between early complications and the following factors: age, sex, body mass index, type of tumor, location of tumor, American Society of Anesthesiologists score, physical status, frailty (categorized by the 5-factor Modified Frailty Index [mFI-5]), neutrophil-to-lymphocyte ratio, C-reactive protein/albumin ratio, preoperative chemotherapy, preoperative radiotherapy, surgical approach, and the number of resected vertebrae. Of the 169 patients, 86 (50.1%) were included in the complication group. Multivariate analysis showed that high mFI-5 scores (odds ratio [OR] = 2.99, p < 0.001) and an increased number of resected vertebrae (OR = 1.87, p = 0.018) were risk factors for postoperative complications. Frailty and the number of resected vertebrae were independent risk factors for postoperative complications after TES for spinal tumors.
- Published
- 2023
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41. Iridoids from Morinda lucida, (Benth.) Rubiaceae, produced analgesic and anti-inflammatory activities via agonism at the kappa and delta opioid receptors, inhibition of COX-2 besides elevation of CAT and SOD activities.
- Author
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Kumatia EK, Ayertey F, Ohta T, Uto T, and Tung NH
- Subjects
- Humans, Cyclooxygenase 2 metabolism, Receptors, Opioid, delta, Catalase, Iridoids pharmacology, Iridoids therapeutic use, Analgesics pharmacology, Analgesics therapeutic use, Anti-Inflammatory Agents pharmacology, Anti-Inflammatory Agents therapeutic use, Pain drug therapy, Plant Extracts pharmacology, Plant Extracts therapeutic use, Carrageenan, Inflammation drug therapy, Antioxidants, Superoxide Dismutase metabolism, Edema chemically induced, Edema drug therapy, Edema metabolism, Morinda, Rubiaceae
- Abstract
Ethnopharmacological Relevance: Pain and inflammation are the major symptoms of almost every human disease. Herbal preparations from Morinda lucida are used to treat pain and inflammation in traditional medicine. However, the analgesic and anti-inflammatory activities of some of the plant's chemical constituents are not known., Aim of the Study: The aim of this study is to evaluate the analgesic and anti-inflammatory activities and possible mechanisms of these activities of iridoids from Morinda lucida., Material and Methods: The compounds were isolated using column chromatography and characterized by NMR spectroscopy and LC-MS. Anti-inflammatory activity was evaluated using carrageenan-induced paw edema. Whereas, the analgesic activity was assessed in the hot plate and acetic acid-induced writhing assays. Mechanistic studies were conducted using pharmacological blockers, determination of antioxidant enzymes, lipid peroxidation, and docking studies., Results: The iridoid, ML2-2 exhibited inverse dose-dependent anti-inflammatory activity (42.62% maximum at 2 mg/kg p. o). ML2-3 produced dose-dependent anti-inflammatory activity (64.52% maximum at 10 mg/kg p. o.). Anti-inflammatory activity of diclofenac sodium was 58.60% at 10 mg/kg p. o. Furthermore, ML2-2 and ML2-3 produced analgesic activity (P < 0.01) of 44.44 ± 5.84 and 54.18 ± 19.01%. at 10 mg/kg p. o. respectively in the hot plate assay and 64.88 and 67.44% in the writhing assay. ML2-2 significantly elevated catalase activity. However, ML2-3 elevated SOD and catalase activity significantly. In the docking studies, both iridoids formed stable crystal complexes with delta and kappa opioid receptors, and the COX-2 enzyme with very low free binding energies (ΔG) from -11.2 to -14.0 kcal/mol. However, they did not bind with the mu opioid receptor. The lower bound RMSD of most of the poses were found to be ≤ 2. Several amino acids were involved in the interactions through various inter molecular forces., Conclusion: These results indicate that ML2-2 and ML2-3 possessed very significant analgesic and anti-inflammatory activities via acting as both delta and kappa opioid receptor agonist, elevation of anti-oxidant activity and inhibition of COX-2., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)
- Published
- 2023
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42. Strong attractive interaction between finite element models of twisted cellulose nanofibers by intermeshing of twists.
- Author
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Uetani K and Uto T
- Abstract
Analysis of the attractive interaction between intrinsically twisted cellulose nanofibers (CNFs) is essential to control the physical properties of the higher-order structures of CNFs, such as paper and spun fiber. In this study, a finite element model reflecting the typical morphology of a twisted CNF was used to analyze the attractive interaction forces between multiple approaching CNF models. For two parallel CNF models, when one of the CNF models was rotated 90° around the long-axis direction, the twisting periods meshed, giving the maximum attraction force. Conversely, when the two CNF models were approaching diagonally, the CNF models were closest at an angle of -3.2° ( i.e. , in left-handed chirality) to give the most stable structure owing to the right-handed twist of the CNF models themselves. Furthermore, the two nematic layers were closest when one nematic layer was approached at an angle of -2° ( i.e. , in left-handed accumulation chirality), resulting in the greatest attraction. The results characterize the unique distribution of the attractive interaction forces between twisted CNF models, and they underscore the importance of chiral management in CNF aggregates, especially intermeshing of twists., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)
- Published
- 2023
- Full Text
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43. Gut dysbiosis promotes the breakdown of oral tolerance mediated through dysfunction of mucosal dendritic cells.
- Author
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Fukaya T, Uto T, Mitoma S, Takagi H, Nishikawa Y, Tominaga M, Choijookhuu N, Hishikawa Y, and Sato K
- Subjects
- Humans, Lymphocytes metabolism, Integrin alpha Chains metabolism, Dendritic Cells metabolism, Anti-Bacterial Agents metabolism, Intestinal Mucosa metabolism, Dysbiosis metabolism, Immunity, Innate
- Abstract
While dysbiosis in the gut is implicated in the impaired induction of oral tolerance generated in mesenteric lymph nodes (MesLNs), how dysbiosis affects this process remains unclear. Here, we describe that antibiotic-driven gut dysbiosis causes the dysfunction of CD11c
+ CD103+ conventional dendritic cells (cDCs) in MesLNs, preventing the establishment of oral tolerance. Deficiency of CD11c+ CD103+ cDCs abrogates the generation of regulatory T cells in MesLNs to establish oral tolerance. Antibiotic treatment triggers the intestinal dysbiosis linked to the impaired generation of colony-stimulating factor 2 (Csf2)-producing group 3 innate lymphoid cells (ILC3s) for regulating the tolerogenesis of CD11c+ CD103+ cDCs and the reduced expression of tumor necrosis factor (TNF)-like ligand 1A (TL1A) on CD11c+ CD103+ cDCs for generating Csf2-producing ILC3s. Thus, antibiotic-driven intestinal dysbiosis leads to the breakdown of crosstalk between CD11c+ CD103+ cDCs and ILC3s for maintaining the tolerogenesis of CD11c+ CD103+ cDCs in MesLNs, responsible for the failed establishment of oral tolerance., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)- Published
- 2023
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44. Development of an indirect competitive enzyme-linked immunosorbent assay for formononetin and its application in a cell-based assay using MC3T3-E1 cells.
- Author
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Fujii S, Ohta T, Ehama R, Irikida M, Nomura S, Shoyama Y, and Uto T
- Subjects
- Animals, Mice, Enzyme-Linked Immunosorbent Assay methods, Hybridomas chemistry, Mice, Inbred BALB C, Isoflavones analysis
- Abstract
Formononetin (FMN) is a methoxy isoflavone found abundantly in leguminous plants and associated foods. Several analytical methods have been developed to detect FMN. However, they are costly, complicated, and time-consuming. This study describes an indirect competitive enzyme-linked immunosorbent assay (icELISA) to determine FMN content in food samples using a monoclonal antibody (mAb) against FMN produced by a newly established hybridoma cell line. Validation studies were conducted, and this assay was found to be sufficiently reliable, with an analytical measurement range of 19.53-1250 ng/mL and a detection limit of 17.42 ng/mL. Furthermore, icELISA was successfully applied for a cell-based assay in which the amount of FMN and ononin uptake was quantified in MC3T3-E1 cells. Hence, icELISA is a simple and reliable method for the detection and quantification of FMN, as well as elucidation of its functions and underlying mechanisms of action., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
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- 2023
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45. A case of severe thrombocytopenia after the first exposure to rifampicin.
- Author
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Nakane C, Nishimoto K, Kishimoto E, Suzuki K, Nakagawa E, Morikawa M, Murakami Y, Aoshima Y, Matsushima S, Harada M, Uto T, and Imokawa S
- Abstract
Severe immune thrombocytopenia is a rare side-effect of rifampicin (RFP) and can be life-threatening. Here, we report the case of a 74-year-old male with tuberculous pleurisy who developed severe thrombocytopenia after first exposure to RFP. Platelet count decreased to 1 × 10
3 /μL after 7 days of treatment with RFP, isoniazid, ethambutol, and pyrazinamide. After all the drugs were discontinued, the platelet count recovered. As thrombocytopenia did not occur after re-administration of drugs other than RFP, the patient was diagnosed with RFP-induced thrombocytopenia. Clinicians should be aware that RFP can induce acute and severe thrombocytopenia even without previous exposure to this drug., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)- Published
- 2023
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46. Angiotensin I-Converting Enzyme-Inhibitory Activity and Phytochemical Profile of Constituents of the Leaves of Rehmannia glutinosa f. hueichingensis.
- Author
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Ohta T, Inoha M, Kawahara C, Toshimitsu S, Shoyama Y, and Uto T
- Subjects
- Peptidyl-Dipeptidase A, Phytochemicals, Pyrans, Rehmannia chemistry
- Abstract
The root of Rehmannia glutinosa Liboschitz forma hueichingensis HSIAO has been used as a tonic and treatment for urinary and skin disorders in Japanese Kampo medicine. Phytochemical investigation of the root has been well reported, but that of the leaves is limited. To explore the potential value of R. glutinosa leaves, we focused on the angiotensin I-converting enzyme (ACE)-inhibitory activity. The leaf extract exhibited ACE-inhibitory activity, and the inhibitory potency of leaves was stronger than that of roots. Using this activity as an indicator, we isolated linaride (1), 6-O-hydroxybenzoyl ajugol (2), acteoside (3), leucosceptoside A (4), martynoside (5), luteolin (6), apigenin (7), and chrysoeriol (8) by separating and purifying the extract. We then examined the ACE-inhibitory activities of 1-8, catalpol (9), aucubin (10), ajugol (11), and echinacoside (12). Among them, 3, 6, and 12 displayed the most potent inhibitory activity. A simultaneous analytical method was also developed using compounds contained in R. glutinosa leaves and roots, and their contents were compared. The method consisted of extraction with 50% aqueous methanol under sonication for 60 min and LC/MS measurement. R. glutinosa leaves tended to have higher levels of majority of the analytes than the roots, including 3 and 6, which had higher ACE-inhibitory activity. These results suggest that 3 and 6 contribute to the ACE-inhibitory activity of R. glutinosa leaves, which may represent a useful medicinal resource for hypertension.
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- 2023
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47. Predictors of poor clinical outcomes including in-hospital death and low ability to perform activities of daily living at discharge in hospitalized patients with chronic obstructive pulmonary disease exacerbation.
- Author
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Murakami Y, Yasui H, Sato J, Uto T, Inui N, Suda T, and Imokawa S
- Subjects
- Humans, Hospital Mortality, Retrospective Studies, Patient Discharge, Hospitalization, Disease Progression, Activities of Daily Living, Pulmonary Disease, Chronic Obstructive diagnosis, Pulmonary Disease, Chronic Obstructive therapy, Pulmonary Disease, Chronic Obstructive complications
- Abstract
Background: Chronic obstructive pulmonary disease (COPD) is a major cause of mortality and morbidity worldwide. Many patients with COPD experience exacerbations that require hospitalization, which is associated with an increased risk of in-hospital death and impaired ability to perform activities of daily living (ADL). Declining ability to perform ADL is a critical issue for these patients., Objectives: To identify predictors of poor clinical outcomes, including in-hospital death and low ability to perform ADL at discharge, in patients who are hospitalized with exacerbation of COPD., Design: This retrospective study involved a cohort of patients with exacerbation of COPD who were admitted to Iwata City Hospital in Japan between July 2015 and October 2019., Methods: We collected clinical data, measured the cross-sectional area of the erector spinae muscles (ESM
CSA ) on computed tomography (CT) scans at admission, and investigated the associations of poor clinical outcomes (in-hospital death and severe dependence when performing ADL, defined as a Barthel Index (BI) of ⩽40 at discharge) with clinical parameters., Results: Overall, 207 patients were hospitalized for exacerbation of COPD during the study period. The incidence of poor clinical outcomes was 21.3%, and the in-hospital mortality rate was 6.3%. Multivariate logistic regression analyses showed that older age, long-term oxygen therapy, an elevated D-dimer concentration, and a reduced ESMCSA on chest CT at admission were significantly associated with poor clinical outcomes (in-hospital death and a BI of ⩽40)., Conclusion: Hospitalization for exacerbation of COPD was associated with high rates of in-hospital mortality and a BI of ⩽40 at discharge, which may be predicted by assessment of ESMCSA .- Published
- 2023
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48. Tunability of the thermal diffusivity of cellulose nanofibril films by addition of multivalent metal ions.
- Author
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Uetani K, Kasuya K, Yoshikawa S, and Uto T
- Subjects
- Cellulose, Cyclic N-Oxides, Oxygen, Polymers, Protons, Nanofibers, Petroleum
- Abstract
Discovering principles to tune the heat-transport properties of cellulose nanofibril (CNF) films will open the door for the development of biomass-derived heat-transfer materials and break away from existing petroleum-based polymer composites. In this study, we added various multivalent metal ions to CNF films with surface carboxy groups formed by 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) oxidation and measured their thermal diffusivities in the dry state by an original method to verify the tunability of the thermal diffusivity. We found that the in-plane thermal diffusivity of the film is inversely proportional to the ionic radius and directly proportional to the Pauling electro-negativity. The CNF film with proton-neutralized carboxyl groups showed the highest level of thermal diffusivity among the films with various metal ions. Molecular dynamics simulations clarified that the spatial distribution of the introduced ions is determined by the closest distance between the cation and carboxylate oxygen atom of the TEMPO-oxidized CNF surface., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
- Published
- 2022
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49. (+)-Magnolin Enhances Melanogenesis in Melanoma Cells and Three-Dimensional Human Skin Equivalent; Involvement of PKA and p38 MAPK Signaling Pathways.
- Author
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Uto T, Tung NH, Ohta T, and Shoyama Y
- Subjects
- Humans, Animals, Microphthalmia-Associated Transcription Factor metabolism, Melanins metabolism, Melanins pharmacology, Monophenol Monooxygenase, Methanol, Cyclic AMP-Dependent Protein Kinases metabolism, p38 Mitogen-Activated Protein Kinases metabolism, Signal Transduction, Cell Line, Tumor, Lignans pharmacology, Melanoma drug therapy, Melanoma metabolism, Melanoma, Experimental drug therapy
- Abstract
Magnoliae Flos is a traditional herbal medicine used to treat nasal congestion associated with headache, empyema, and allergic rhinitis. In our preliminary screening of crude drugs used in Japanese Kampo formulas for melanin synthesis, the methanol extract of Magnoliae Flos was found to exhibit strong melanin synthesis activity. However, there have been no studies evaluating the effects of Magnoliae Flos or its constituents on melanogenesis. The present study aimed to isolate the active compounds from Magnoliae Flos that activate melanin synthesis in melanoma cells and three-dimensional human skin equivalent, and to investigate the molecular mechanism underlying melanin induction. The methanol extract of Magnoliae Flos induced an increase of melanin content in both B16-F1 and HMV-II cells. A comparison of melanin induction by three fractions prepared from the extract showed that the ethyl acetate fraction markedly induced melanin synthesis. Bioassay-guided separation of the ethyl acetate fraction resulted in the isolation of seven lignans (1: - 7: ). Among them, (+)-magnolin (5: ) strongly induced melanin synthesis and intracellular tyrosinase activity. Furthermore, the ethyl acetate fraction and 5: clearly induced melanin content in a three-dimensional human skin equivalent. Molecular analysis revealed that 5: triggered the protein expression of tyrosinase, tyrosinase-related protein-1, and tyrosinase-related protein-2. Further analysis of transcriptional factors and signaling pathways demonstrated that 5: induces the protein expression of tyrosinase, tyrosinase-related protein-1, and tyrosinase-related protein-2 activated by the protein kinase A- and p38 mitogen-activated protein kinase-dependent pathways, leading to cAMP-responsive element-binding protein phosphorylation and microphthalmia-associated transcription factor expression. These findings demonstrate the potential of 5: as a potent therapeutic agent for hypopigmentation., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)
- Published
- 2022
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50. BNT162b2 coronavirus disease-2019 vaccination accelerated rheumatoid arthritis disease activity in chronic eosinophilic pneumonia: A case report.
- Author
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Morikawa MM, Harada M, Kishimoto E, Suzuki K, Nakagawa E, Hiramatsu T, Nakai S, Murakami Y, Nishimoto K, Matsushima S, Uto T, and Imokawa S
- Subjects
- Aged, 80 and over, Anti-Inflammatory Agents, BNT162 Vaccine, Female, Humans, Inflammation, Methylprednisolone therapeutic use, Rheumatoid Factor, Vaccination, Arthritis, Rheumatoid complications, Arthritis, Rheumatoid diagnosis, Arthritis, Rheumatoid drug therapy, COVID-19 prevention & control, COVID-19 Vaccines adverse effects, Pulmonary Eosinophilia etiology
- Abstract
Rationale: The relationship between rheumatoid arthritis (RA) and eosinophilic inflammation is unclear. According to recent studies, it has been suggested that T helper 2 cell responses play a role in the inhibition of RA. It is unclear how the immunological response after coronavirus disease-2019 (COVID-19) vaccination affects T cell immune reactions., Patient Concerns and Diagnoses: Here, we report the case of an 88-year-old woman diagnosed with RA and chronic eosinophilic pneumonia (CEP). She was diagnosed with CEP about 20 years ago, and, through steroid treatment, she improved and had no relapse for 16 years. At the time of diagnosis of CEP, the rheumatoid factor (RF) was increased; however, there were no joint symptoms. After receiving the COVID-19 vaccine, joint and respiratory symptoms gradually worsened. Laboratory examinations showed increased RF, anti-cyclin citrullinated peptide antibody, and peripheral absolute eosinophil count. Musculoskeletal ultrasonography showed synovitis., Intervention and Outcome: Methylprednisolone pulse therapy improved respiratory and joint symptoms immediately; RA and CEP stabilized with no relapses., Lessons: Eosinophilic and rheumatoid reactions following COVID-19 vaccination were an-reported adverse events. Eosinophilic inflammation might be reflected on an anti-inflammatory reaction in initial phase of RA., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)
- Published
- 2022
- Full Text
- View/download PDF
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