Publications by authors named "Yuki Saito"

263 Publications

1.2-µm-band ultrahigh-Q photonic crystal nanocavities and their potential for Raman silicon lasers.

Opt Express 2021 Jul;29(15):24396-24410

Nanocavity devices based on silicon that can operate in the 1.2-µm band would be beneficial for several applications. We fabricate fifteen cavities with resonance wavelengths between 1.20 and 1.23 µm. Experimental quality (Q) factors larger than one million are obtained and the average Q values are lower for shorter wavelengths. Furthermore, we observe continuous-wave operation of a Raman silicon laser with an excitation wavelength of 1.20 µm and a Raman laser wavelength of 1.28 µm. The Q values of the nanocavity modes used to confine the excitation light and the Raman scattered light are about half of those for our Raman silicon laser operating in the 1.55-µm band. Nevertheless, this device exhibits an input-output characteristic with a clear laser threshold. Finally, we consider the effect of the higher scattering probability at shorter wavelengths on the Raman laser performance in the 1.2-µm band.
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http://dx.doi.org/10.1364/OE.431721DOI Listing
July 2021

An enriched environment prevents cognitive impairment in an Alzheimer's disease model by enhancing the secretion of exosomal microRNA-146a from the choroid plexus.

Brain Behav Immun Health 2020 Dec 22;9:100149. Epub 2020 Sep 22.

Department of Anatomy, Sapporo Medical University, School of Medicine, Sapporo, Hokkaido, Japan.

Alzheimer's disease (AD) is characterized by the extensive deposition of amyloid-β plaques and neurofibrillary tangles. We previously found that preserved function of astrocytes is associated with cognitively normal subjects with AD pathology. Here we show that an enriched environment (EE) can prevent cognitive impairment in AD model mice by ameliorating astrocytic inflammation and increasing synaptic density in the subiculum area of the hippocampus. In AD model mice treated with an EE, increased levels of microRNA (miR)-146a and down-regulation of NF-κB were observed in the hippocampus. In addition, increased levels of interferon (IFN)-γ were seen in serum from mice exposed to an EE. , enhanced miR-146a expression was observed in exosomes derived from the choroid plexus (CP) after IFN-γ treatment. In further experiments, we transfected miR-146a into Aβ/lipopolysaccharide-induced inflammatory astrocytes and showed that miR-146a ameliorated astrocytic inflammation by down-regulating tumor necrosis factor receptor-associated factor 6 and NF-κB. The present study indicates that following an EE, exosomal miR-146a derived from the CP cells is a key factor in ameliorating astrocytic inflammation, leading to synaptogenesis and correction of cognitive impairment.
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http://dx.doi.org/10.1016/j.bbih.2020.100149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474441PMC
December 2020

Diverse Roles of Cellular Senescence in Skeletal Muscle Inflammation, Regeneration, and Therapeutics.

Front Pharmacol 2021 6;12:739510. Epub 2021 Sep 6.

Department of Anatomy, Sapporo Medical University School of Medicine, Sapporo, Japan.

Skeletal muscle undergoes vigorous tissue remodeling after injury. However, aging, chronic inflammatory diseases, sarcopenia, and neuromuscular disorders cause muscle loss and degeneration, resulting in muscular dysfunction. Cellular senescence, a state of irreversible cell cycle arrest, acts during normal embryonic development and remodeling after tissue damage; when these processes are complete, the senescent cells are eliminated. However, the accumulation of senescent cells is a hallmark of aging tissues or pathological contexts and may lead to progressive tissue degeneration. The mechanisms responsible for the effects of senescent cells have not been fully elucidated. Here, we review current knowledge about the beneficial and detrimental effects of senescent cells in tissue repair, regeneration, aging, and age-related disease, especially in skeletal muscle. We also discuss how senescence of muscle stem cells and muscle-resident fibro-adipogenic progenitors affects muscle pathologies or regeneration, and consider the possibility that immunosenescence leads to muscle pathogenesis. Finally, we explore senotherapy, the therapeutic targeting of senescence to treat age-related disease, from the standpoint of improving muscle regeneration.
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http://dx.doi.org/10.3389/fphar.2021.739510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8450382PMC
September 2021

Mechanism of charge accumulation of poly(heptazine imide) gel.

Sci Rep 2021 Sep 8;11(1):17833. Epub 2021 Sep 8.

Department of Physics, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.

Photo-stimuli response in materials is a fascinating feature with many potential applications. A photoresponsive gel of poly(heptazine imide), PHI, termed PHIG, exhibits photochromism, photoconductivity, and photo-induced charge accumulation, and is generated using ionic liquids and PHI. Although there are several examples of ionic liquid gels that exhibit photochromism and photoconductivity, this is the first report of an ionic liquid gel that exhibits both these properties as well as charge accumulation. We conducted experimental and theoretical investigations to understand the mechanism of the photostimulus response of PHIG, especially charge accumulation. The proposed model explains both the mechanism of charge accumulation and dark photocatalysis by PHI and provides new concepts in the field of photofunctional materials.
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http://dx.doi.org/10.1038/s41598-021-97025-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426363PMC
September 2021

A Patient with a Unilateral Insular Lesion Showing Bilaterally Reduced Perception of Noxious Stimulation.

Intern Med 2021 Aug 24. Epub 2021 Aug 24.

Department of Occupational Therapy, Graduate School of Health Sciences, Yamagata Prefectural University of Health Sciences, Japan.

No study has reported a unilateral localized cerebral lesion of the posterior insula bilaterally reducing noxious stimuli perception. A 57-year-old man with an infarct involving the right posterior insula presented with reduced somatosensory response in the upper and lower left extremities. Furthermore, there was a reduced response to noxious stimulation in the right upper and lower limbs. We noted reductions in pain, noxious heat and cold perceptions, and sensitivity to increasing temperature. Other somatic sensations, including non-noxious temperatures, remained intact in the right upper and lower extremities. These findings in our patient with a unilateral insular lesion indicated a bilaterally reduced perception of noxious stimulation.
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http://dx.doi.org/10.2169/internalmedicine.6878-20DOI Listing
August 2021

Effect of short-time treatment with TNF-α on stem cell activity and barrier function in enteroids.

Cytotechnology 2021 Aug 16;73(4):669-682. Epub 2021 Jul 16.

Department of Nutritional Science, Faculty of Applied Bioscience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo, 156-8502 Japan.

Although tumor necrosis factor-α (TNF-α) is a known major inflammatory mediator in inflammatory bowel disease (IBD) and has various effects on intestinal epithelial cell (IEC) homeostasis, the changes in IECs in the early inflammatory state induced during short-time treatment (24 h) with TNF-α remain unclear. In this study, we investigated TNF-α-induced alterations in IECs in the early inflammatory state using mouse jejunal organoids (enteroids). Of the inflammatory cytokines, i.e., TNF-α, IL-1β, IL-6, and IL-17, only TNF-α markedly increased the mRNA level of macrophage inflammatory protein 2 (MIP-2; the mouse homologue of interleukin-8), which is induced in the early stages of inflammation. TNF-α stimulation (3 h and 6 h) decreased the mRNA level of the stem cell markers leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) and polycomb group ring finger 4 and the progenitor cell marker prominin-1, which is also known as CD133. In addition, TNF-α treatment (24 h) decreased the number of Lgr5-positive cells and enteroid proliferation. TNF-α stimulation at 3 h and 6 h also decreased the mRNA level of chromogranin A and mucin 2, which are respective markers of enteroendocrine and goblet cells. Moreover, enteroids treated with TNF-α (24 h) not only decreased the integrity of tight junctions and cytoskeletal components but also increased intercellular permeability in an influx test with fluorescent dextran, indicating disrupted intestinal barrier function. Taken together, our findings indicate that short-time treatment with TNF-α promotes the inflammatory response and decreases intestinal stem cell activity and barrier function.

Supplementary Information: The online version contains supplementary material available at 10.1007/s10616-021-00487-y.
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http://dx.doi.org/10.1007/s10616-021-00487-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319277PMC
August 2021

Prognostic Value of Liver Stiffness Measured by Two-Dimensional Elastography in Acute Decompensated Heart Failure with Preserved Ejection Fraction.

Int Heart J 2021 Jul 17;62(4):821-828. Epub 2021 Jul 17.

Division of Cardiology, Department of Medicine, Nihon University School of Medicine.

Liver stiffness (LS) assessed by ultrasound elastography reflects right-sided filling pressure and offers additional prognostic information in patients with acute decompensated heart failure (ADHF). However, the prognostic value of LS in heart failure (HF) with preserved ejection fraction (HFpEF) remains unclear. This study aimed to investigate the prognostic value of LS measured by two-dimensional shear wave elastography (2D-SWE) in patients with HFpEF.We prospectively enrolled 80 patients hospitalized for decompensated HFpEF between September 2019 and June 2020. Patients were categorized into three groups based on the tertile values of LS at discharge.The third tertile LS group had an older age; more advanced New York Heart Association functional class; higher total bilirubin, γ-glutamyl transferase (GGT), N-terminal pro-B type natriuretic peptide (NT pro-BNP), and Fibrosis-4 index; a larger right ventricle diastolic diameter, higher tricuspid regurgitation pressure gradient, and a larger maximal inferior vena cava diameter. During a median [interquartile range] follow-up period of 212 (82-275) days, 25 (31.2%) patients suffered composite end points (all-cause mortality and rehospitalization for worsening HF). The third tertile LS group had a significantly higher rate of composite end points (log-rank P = 0.002). A higher LS and the third tertile LS were significantly associated with the composite end points, even after adjusting for a conventional validated HF risk score and other previously reported prognostic risk factors.Increased LS measured by 2D-SWE reflects the severity of liver impairment by liver congestion and fibrosis, underlying right HF, and provides additional information for the prediction of poor outcomes in HFpEF.
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http://dx.doi.org/10.1536/ihj.21-025DOI Listing
July 2021

Computed tomography assessment of mandibular morphologic changes and the inferior mandibular border defect after sagittal split ramus osteotomy.

Oral Surg Oral Med Oral Pathol Oral Radiol 2021 Feb 23:4579. Epub 2021 Feb 23.

Department of Oral and Maxillofacial Surgery, Division of Medicine, Interdisciplinary Graduate School, University of Yamanashi, Chuo-shi, Yamanashi, Japan.

Objective: This study aimed to assess mandibular morphologic changes to the condyle, ramus, mandibular body, and inferior mandibular border defect after sagittal split ramus osteotomy in class II and III patients.

Study Design: The relationships among the condyle, ramus, and mandibular body measured by computed tomography preoperatively and postoperatively were assessed and factors related to the reduction of the condylar square and mandibular inferior border defect were examined.

Results: Patients included 72 female patients with jaw deformity (36 skeletal class II cases, 36 skeletal class III cases). Postoperative reduction of the condylar square was significantly correlated with preoperative condylar height in patients with class II (P = .0297) vs preoperative condylar height and preoperative mandibular height in patients with class III (P < .0001). A mandibular inferior border defect was found in 18 of 72 class II sides (25.0%) and was significantly related to the position of the osteotomy line and attachment side of the inferior border cortex (P < .0001).

Conclusions: This study's findings suggest that the postoperative reduction of the condyle could be associated with preoperative condylar height. However, the mandibular inferior border defect in class II advancement surgery could be independently associated with technical factors in sagittal split ramus osteotomy.
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http://dx.doi.org/10.1016/j.oooo.2021.02.010DOI Listing
February 2021

Evaluation of Nasal Function and Upper Airway Morphology After Bi-Maxillary Surgery Using Rhinomanometry and Computed Tomography.

J Craniofac Surg 2021 Jul 13. Epub 2021 Jul 13.

Department of Oral and Maxillofacial Surgery, Division of Medicine, interdisciplinary Graduate School, University of Yamanashi, Chuoshi, Japan.

Purpose: This study was performed to evaluate changes in nasal airflow, nasal airway resistance, nasal cross-sectional area, pharyngeal horizontal area, nasopharyngeal and oropharyngeal volume following Le Fort I osteotomy (L1) impaction with sagittal split ramus osteotomy (SSRO) in classes II and III.

Materials And Methods: The subjects consisted of 35 patients (6 males and 29 females, 70 sides) 17 of which were diagnosed as class II and 18 as class III who underwent L1 and SSRO. Nasal airflow and resistance were measured using the rhinomanometry system (GM NR-6 EXECUTIVE) before and at 1 and 6 months after surgery. Nasal, cross-sectional area, and volume were measured using a 3-dimensional computed tomography respectively, before and 1-year after surgery.

Results: Although a significant decrease was found in nasal volume after surgery (P = 0.0042), there was no difference between before and after surgery in the nasal airway resistance in class II.A significant decrease in nasal volume was found after surgery (P = 0.0005) and there were no postoperative changes in both nasal airflow and resistance in class III.

Conclusion: The study suggested that L1 impaction with SSRO did not worsen nasal function such as nasal airflow and nasal airway resistance, although nasal volume significantly decreased in both groups.
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http://dx.doi.org/10.1097/SCS.0000000000007958DOI Listing
July 2021

Association between the health insurance status and clinical outcomes among patients with acute heart failure in Japan.

Heart Vessels 2021 Jun 22. Epub 2021 Jun 22.

Division of Cardiology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo, 173-8610, Japan.

The relationship between the socioeconomic status, including the health insurance status, and prognosis of heart failure (HF) has been recognized as an important concept for stratifying the risk in HF patients and is gaining increasing attention worldwide even in countries with a universal healthcare system. However, the impact of the Japanese health insurance status on outcomes among patients admitted for acute HF has not been fully clarified. We enrolled 771 patients admitted for acute HF between January 2018 and December 2019 and collected data on the in-hospital mortality, length of the hospital stay, and cardiac events, defined as cardiovascular death and readmission for HF within 1 year after discharge. Patients were divided into two groups according to their insurance status, i.e., public assistance (n = 87) vs. other insurance (n = 684). The public assistance group was significantly younger and had a higher rate of diabetes, smoking, ischemic and hypertensive heart disease, and low estimated glomerular filtration rate (all P < 0.05). Pharmacological/invasive heart failure therapy, in-hospital mortality, and the 90-day cardiac event rate after discharge did not differ between the groups. However, the public assistance group had a significantly higher 1-year cardiac event rate than the other insurance groups (P = 0.025). After adjusting for covariates, public assistance was independently associated with the 1-year cardiac event rate (HR: 2.15, 95% CI: 1.42-3.26, P < 0.001). Acute HF patients covered by public assistance received the same quality of medical care, including invasive therapy. As a result, no health disparities were found in terms of the in-hospital mortality and 90-day cardiac event rate, unlike overseas surveys. Nevertheless, HF patients with public assistance had a higher risk for the long-term prognosis than those with other insurance. Comprehensive HF management is required post-discharge.
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http://dx.doi.org/10.1007/s00380-021-01895-yDOI Listing
June 2021

Does surgical treatment for unstable fragility fracture of the pelvis promote early mobilization and improve survival rate and postoperative clinical function?

Eur J Trauma Emerg Surg 2021 Jun 22. Epub 2021 Jun 22.

Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Purpose: This retrospective multicenter study aimed to compare rates of early mobilization and survival and functional outcome of surgical treatment (S) with that of conservative treatment (C) according to each unstable fragility fracture of the pelvis (FFP) classification type with displacement of the posterior component ≥ 5 mm.

Methods: We analyzed 64 patients with unstable type III and IV FFP who could move and transfer themselves before injury and had ≥ 5 mm displacement of the posterior component. We compared survival rate, early mobilization, walking ability at final follow-up, and complications at admission for each type of surgical and conservative treatment.

Results: Most of the unstable FFP were type IIIa and IVb in the study population. Type III comprised 40 cases (group S:13/group C:27) and type IV comprised 24 cases (group S:7/group C:17). There were no significant differences in 3 month and 1 year survival rates, although group C (III) had the tendency of higher mortality rate (p = 0.08). Mobilization (transferring to a wheelchair) was enabled significantly earlier in group S (III) than in group C (III) (p = 0.02), but in type IV, most patients enabled early mobilization even without surgical intervention. There were no significant differences in hospital complications and walking ability at final follow-up.

Conclusion: In this study, the superiority of surgical treatment for unstable FFP was not proven. However, the results suggest that type IVb may be a relatively stable type compared to type III and that type IVb should be considered separately from bilaterally complete unstable sacral fractures due to high-energy trauma.
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http://dx.doi.org/10.1007/s00068-021-01729-6DOI Listing
June 2021

Detection of negatively ionized air by using a Raman silicon nanocavity laser.

Opt Express 2021 May;29(11):16228-16240

The performance of a Raman silicon laser based on a high quality-factor nanocavity depends on the degree of free-carrier absorption, and this characteristic may be useful for certain applications. Here we demonstrate that laser oscillation in a Raman silicon nanocavity laser stops abruptly after an exposure to a weak flux of negatively ionized air for a few seconds. Spectral measurements reveal that the laser interruption is mainly caused by the transfer of extra electrons from the negatively ionized air molecules to the silicon nanocavity. These electrons affect the efficiency of the Raman laser by free carrier absorption. We find that the laser output gradually recovers as the extra electrons escape from the nanocavity and confirm that such a detection of ionized air is repeatable. These results show that a Raman silicon nanocavity laser can be used for the detection of ionized air with a high spatial resolution.
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http://dx.doi.org/10.1364/OE.423475DOI Listing
May 2021

[PATHOGENESIS OF SEVERE CUTANEOUS ADVERSE REACTIONS: NECROPTOSIS IN STEVENS-JOHNSON SYNDROME/TOXIC EPIDERMAL NECROLYSIS].

Arerugi 2021;70(4):282-288

Division of Dermatology, Niigata University Graduate School of Medical and Dental Sciences.

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http://dx.doi.org/10.15036/arerugi.70.282DOI Listing
July 2021

Effects of gait training with a voluntary-driven wearable cyborg, Hybrid Assistive Limb (HAL), on quality of life in patients with neuromuscular disease, able to walk independently with aids.

J Clin Neurosci 2021 Jul 15;89:211-215. Epub 2021 May 15.

Department of Orthopaedic Surgery, Hirosaki University, Graduate School of Medicine, Japan.

Robot-assisted gait training using a voluntary-driven wearable cyborg, Hybrid Assistive Limb (HAL), has been shown to improve the mobility of patients with neurological disorders; however, its effect on the quality of life (QOL) of patients is not clear. The aim of this study was to assess the effects of HAL-assisted gait training on QOL and mobility in patients with neuromuscular diseases (NMDs). Ten patients with NMDs (seven men and three women, mean age: 57 ± 11 years), with impairment in mobility but could walk alone with aids underwent two courses of gait training with HAL over 6 months, and the single course consisted of nine sessions of training for 4 weeks. We compared the findings of the 2 min walk test, 10 m walk test, the Short Form-36 (SF-36) questionnaire, and the Hospital Anxiety and Depression Scale at baseline, after the 1st training, before the 2nd training, and after the 2nd training using the Friedman test. A significant improvement was observed in the 2 min walking distance from baseline (93 ± 50 m) to after the 2nd training (115 ± 48 m, P = 0.034), as well as in the domains of vitality (P = 0.019) and mental component summary score (P = 0.019) of SF-36. The improvement in 10 m walking speed was significantly correlated with that in the physical functioning (R = 0.831, P = 0.003) and role physical (R = 0.697, P = 0.025) domains in the SF-36. Our findings suggest that HAL-assisted gait training is effective in improving QOL associated with mental health as well as gait ability in selected patients with NMDs.
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http://dx.doi.org/10.1016/j.jocn.2021.04.038DOI Listing
July 2021

Isolation of Simplicillium sympodiophorum and Toxicocladosporium irritans from the Blowout Air of Household Air Conditioners.

Biocontrol Sci 2021 ;26(2):105-111

FCG Research Institute, Inc.

Household air conditioners are known to be contaminated with dematiaceous fungi such as genus Toxicocladosporium and genus Cladosporium. We frequently encounter cases in which a large amount of fungi, which are presumed to belong to the family Cordycipitaceae, are isolated from the blowout air of the household air conditioners. Therefore, the Cordycipitaceae isolated in the survey of four cases of the air conditioners were identified by genetic analyses. As a result, all of them were found to be Simplicillium sympodiophorum. The concentration of airborne fungi, S. sympodiophorum in the blowout air was high (> 10 cfu/m) as exceeding the upper limit of quantification in three of four cases, and 5,000 cfu/m in one case. This study revealed that S. sympodiophorum contaminated multiple air conditioners. Genus Toxicocladosporium was also isolated from the two air conditioners, and it was found to be Toxicocladosporium irritans by the genetic analysis.
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http://dx.doi.org/10.4265/bio.26.105DOI Listing
January 2021

Interaction between Orexin Neurons and Monoaminergic Systems.

Front Neurol Neurosci 2021 28;45:11-21. Epub 2021 May 28.

International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Japan.

Orexins have received a lot of attention as potent endogenous arousal-promoting peptides, and orexin receptor antagonists have shown clinical efficacy for the treatment of insomnia. Orexin neurons are thought to act primarily on monoaminergic neurons to maintain arousal and vigilance. In this chapter, we discuss the functional interaction between monoaminergic systems, including noradrenaline, serotonin and histamine, and orexin neurons, as well as interactions between the acetylcholine system and the orexin neurons, focusing, in particular, on their function in the regulation of sleep-wakefulness states. Orexin also has close interactions with the dopaminergic system, and many studies have suggested roles of orexin signaling in the reward system and roles for orexins in drug addiction.
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http://dx.doi.org/10.1159/000514955DOI Listing
May 2021

Comprehensive assessment of left atrial and ventricular remodeling in paroxysmal atrial fibrillation by the cardiovascular magnetic resonance myocardial extracellular volume fraction and feature tracking strain.

Sci Rep 2021 05 25;11(1):10941. Epub 2021 May 25.

Department of Cardiovascular Medicine, Nihon University Graduate School, 30-1 Oyaguchi kamimachi, Itabashi, Tokyo, 173-8610, Japan.

Atrial fibrillation (AF) is a progressive disease that starts with structural or functional changes in the left atrium and left ventricle, and evolves from paroxysmal toward sustained forms. Early detection of structural or functional changes in the left atrium and left ventricle in the paroxysmal stage could be useful for identifying a higher risk of progression to persistent AF and future cardio-cerebrovascular events. The aim of this study was to test the hypothesis that the feature tracking (FT) left atrial (LA) strain and left ventricular (LV) extracellular volume fraction (ECV) derived from cardiovascular magnetic resonance (CMR) could detect early changes in remodeling of the left atrium and ventricle in the paroxysmal AF (PAF) stage. The participants were comprised of 106 PAF patients (age, 66.1 ± 10.7 years; 66% male) who underwent clinical CMR before pulmonary vein isolation and 20 control subjects (age, 68.3 ± 8.6 years; 55% male). The CMR-FT LA strain/phasic function and LV-ECV were compared between the PAF and control groups. The total and passive LA empty fraction (LAEF) and LA strain (corresponding to LA reservoir and conduit function) were decreased in the PAF group as compared to the control group. However, active LAEF (corresponding to the LA booster pump function) did not differ significantly between the PAF group (33.9 ± 10.9%) and control group (37.9 ± 13.3%, p = 0.15), while the active LA strain (corresponding to the LA booster pump function) was significantly decreased in the PAF group (11.4 ± 4.3 vs. 15.2 ± 5.6%, p = 0.002). The LV-ECV was significantly greater in the PAF group (28.7 ± 2.8%) than control group (26.6 ± 2.0%, p = 0.002). In the PAF group, the LV-ECV correlated significantly with the E/e' and LA volume index. Regarding the LA strain, correlations were seen between the LV-ECV and both the reservoir function and conduit function. CMR-FT LA strain in combination with the LV-ECV in a single clinical study offers a potential imaging marker that identifies LA/LV remodeling including subtle LA booster pump dysfunction undetectable by the conventional booster pump LAEF in the PAF stage.
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http://dx.doi.org/10.1038/s41598-021-90117-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149643PMC
May 2021

A nanogel-based trivalent PspA nasal vaccine protects macaques from intratracheal challenge with pneumococci.

Vaccine 2021 06 17;39(25):3353-3364. Epub 2021 May 17.

Department of Mucosal Immunology, IMSUT Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; HanaVax Inc., Tokyo 103-0012, Japan; Mucosal Immunology and Allergy Therapeutics, Institute for Global Prominent Research, Chiba University, Chiba 263-8522, Japan; CU-UCSD Center for Mucosal Immunology, Allergy and Vaccine (cMAV), Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0063, United States. Electronic address:

Current polysaccharide-based pneumococcal vaccines are effective but not compatible with all serotypes of Streptococcus pneumoniae. We previously developed an adjuvant-free cationic nanogel nasal vaccine containing pneumococcal surface protein A (PspA), which is expressed on the surfaces of all pneumococcal serotypes. Here, to address the sequence diversity of PspA proteins, we formulated a cationic nanogel-based trivalent pneumococcal nasal vaccine and demonstrated the vaccine's immunogenicity and protective efficacy in macaques by using a newly developed nasal spray device applicable to humans. Nasal vaccination of macaques with cationic cholesteryl pullulan nanogel (cCHP)-trivalent PspA vaccine effectively induced PspA-specific IgGs that bound to pneumococcal surfaces and triggered complement C3 deposition. The immunized macaques were protected from pneumococcal intratracheal challenge through both inhibition of lung inflammation and a dramatic reduction in the numbers of bacteria in the lungs. These results demonstrated that the cCHP-trivalent PspA vaccine is an effective candidate vaccine against pneumococcal infections.
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http://dx.doi.org/10.1016/j.vaccine.2021.04.069DOI Listing
June 2021

Evaluation of condylar surface CT values related to condylar height reduction after orthognathic surgery.

J Craniomaxillofac Surg 2021 Aug 30;49(8):639-648. Epub 2021 Jan 30.

Department of Oral and Maxillofacial Surgery, Division of Medicine, Interdisciplinary Graduate School, University of Yamanashi, 1110 Shimokato, Chuo Yamanashi, 409-3893, Japan.

This study was performed to evaluate the relationship between condylar height reduction and changes in condylar surface computed tomography (CT) values in jaw deformity patients following orthognathic surgery. Mandibular advancement by sagittal split ramus osteotomy (SSRO) with Le Fort I osteotomy was performed in class II patients, and mandibular setback by SSRO with Le Fort I osteotomy was performed in class III patients. The maximum CT values (pixel values) at five points on the condylar surface and the condylar height, ramus height, condylar square, ramus angle, and gonial angle in the sagittal plane were measured preoperatively and 1 year postoperatively. Disc position was classified as anterior disc displacement (ADD) or other types by using magnetic resonance imaging (MRI). Ninety-two condyles of 46 female patients were prepared for this study. Their temporomandibular joints (TMJs) were divided into two groups based on class (46 joints in class II and 46 joints in class III) and two groups based on the findings (25 joints with ADD and 67 joints with other findings). ADD with and without reduction was observed in two joints in the class III group and in 23 joints in the class II group. The distribution of ADD incidence had not changed 1 year after surgery. Condylar height decreased 1 year after surgery in both class II patients (mandibular advancement) (p < 0.0001) and class III patients (mandibular setback) (p = 0.0306). Similarly, condylar height decreased 1 year after surgery both in patients who showed ADD (p = 0.0087) and those with other types (p = 0.0023). Significant postoperative increases at all angle sites on the condylar surface were found in the class II (p < 0.05) and ADD (p < 0.05) groups. This study showed that an enhanced condylar surface CT value might be one sign of condylar height reduction related to sequential condylar resorption, in combination with ADD.
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http://dx.doi.org/10.1016/j.jcms.2021.01.005DOI Listing
August 2021

Self-promoted solid-state covalent networking of Au(SR) through reversible disulfide bonds. A critical effect of the nanocluster in oxidation processes.

Nanoscale 2021 Jun 12;13(22):9971-9977. Epub 2021 May 12.

Graduate School of Environmental Science, Hokkaido University, North 10 West 5, Sapporo 060-0810, Japan.

Covalent crosslinking of ligand-protected gold nanoclusters offers interesting platforms to investigate the properties associated with the synergetic effects of multiple nanoclusters. In this paper, we report the synthesis of covalent networks of [Au(SR)] nanoclusters using reversible disulfide linkages, which was facilitated by the unique capabilities of the nanocluster to mediate oxidation processes. The conventional Au synthesis using 1,6-hexanedithiol afforded a soluble oligodisulfide-appended [Au(SR)] monomer possessing uncoordinated anionic thiolate sites at the terminal ends. Upon exposure to O, the monomer spontaneously underwent intercluster crosslinking in the solid state to give free-standing transparent films, in which the nanoclusters were condensed with the retention of the original Au framework. Through studies combined with model experiments, the Au cluster was found to be involved in the O-mediated radical reactions, promoting the formation of intercluster disulfide linkages. The composition of the films implied the involvement of reversible exchange reactions between disulfide and thiyl radicals, from which it was suggested that solid-state crosslinking occurred in adaptive manners under the control of dynamic covalent chemistry. We also demonstrate that the nanocluster film can serve as a robust and efficient heterogeneous photosensitizer to mediate the generation of singlet oxygen. This work demonstrates a unique aspect of the Au(SR)-type nanocluster to mediate oxidation processes as well as the utility of the concept of dynamic covalent chemistry in the bottom-up construction of nanomaterials, which would widen the potential of ligand-protected nanoclusters.
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http://dx.doi.org/10.1039/d1nr01812dDOI Listing
June 2021

Analysis of 3-D Kinematics Using H-Gait System during Walking on a Lower Body Positive Pressure Treadmill.

Sensors (Basel) 2021 Apr 8;21(8). Epub 2021 Apr 8.

Faculty of Health Sciences, Hokkaido University, Sapporo 060-0812, Japan.

Recently, treadmills equipped with a lower-body positive-pressure (LBPP) device have been developed to provide precise body weight support (BWS) during walking. Since lower limbs are covered in a waist-high chamber of an LBPP treadmill, a conventional motion analysis using an optical method is impossible to evaluate gait kinematics on LBPP. We have developed a wearable-sensor-based three-dimensional motion analysis system, H-Gait. The purpose of the present study was to investigate the effects of BWS by a LBPP treadmill on gait kinematics using an H-Gait system. Twenty-five healthy subjects walked at 2.5 km/h on a LBPP treadmill under the following three conditions: (1) 0%BWS, (2) 25%BWS and (3) 50%BWS conditions. Acceleration and angular velocity from seven wearable sensors were used to analyze lower limb kinematics during walking. BWS significantly decreased peak angles of hip adduction, knee adduction and ankle dorsiflexion. In particular, the peak knee adduction angle at the 50%BWS significantly decreased compared to at the 25%BWS ( = 0.012) or 0%BWS ( < 0.001). The present study showed that H-Gait system can detect the changes in gait kinematics in response to BWS by a LBPP treadmill and provided a useful clinical application of the H-Gait system to walking exercises.
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http://dx.doi.org/10.3390/s21082619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068341PMC
April 2021

Fatal Embolic ST-Elevation Myocardial Infarction Secondary to Healed-Phase Mitral Valve Infective Endocarditis.

Int Heart J 2021 Mar 17;62(2):432-436. Epub 2021 Mar 17.

Division of Cardiology, Department of Medicine, Nihon University School of Medicine.

Embolic myocardial infarction (MI) caused by infective endocarditis (IE) is rare, but it is increasingly recognized as an important complication. This complication typically occurs in patients with aortic valve endocarditis during the acute phase of the infection. It is also known to have a high mortality rate; however, the best practice for its management is unclear owing to scarce available data. In addition, most cases of embolic acute MI (AMI) caused by IE are indirectly diagnosed with a combination of angiographic examination such as coronary angiography or cardiac computed tomography. Herein, we report a case of fatal embolic ST-elevation MI (STEMI) caused by mitral valve IE during the healed phase, which was clearly proven by the pathology findings.
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http://dx.doi.org/10.1536/ihj.20-548DOI Listing
March 2021

Massive perianal skin ulcer due to long-standing amoebic infection in an HIV-negative, heterosexual man.

J Dermatol 2021 Apr 13;48(4):e198-e200. Epub 2021 Feb 13.

Division of Dermatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

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http://dx.doi.org/10.1111/1346-8138.15800DOI Listing
April 2021

A retrospective analysis of radiotherapy in the treatment of external auditory canal carcinoma.

Mol Clin Oncol 2021 Mar 13;14(3):45. Epub 2021 Jan 13.

Department of Radiology, The University of Tokyo Hospital, Bunkyo-ku, Tokyo 113-8655, Japan.

External auditory canal carcinoma (EACC) is a rare disease. The current study aimed to evaluate the clinical outcomes of patients treated with external beam radiotherapy (EBRT) for EACC. The present study retrospectively reviewed 34 consecutive patients treated for EACC with EBRT between February 2001 and January 2019 at the University of Tokyo Hospital. Clinical staging was performed according to the modified Pittsburgh classification. Of all the included patients, seven patients were in the early stages (I or II) and 27 in the advanced stages (III or IV) of EACC. A total of 16 patients underwent EBRT and surgery (S+RT) pre- and/or postoperatively, while 18 patients underwent definitive radiotherapy (dRT). The median prescribed doses for the S+RT and dRT groups were 66 and 70 Gy, respectively. The median follow-up period for all patients was 22.4 months (range, 2-205 months). The 5-year overall survival rates of the S+RT and dRT groups were 66.7 and 45.1%, respectively. The progression-free survival rate at 5-year was 55.6% (95% confidence interval: 36.5-71.1%) for the entire cohort. A total of 14 patients experienced disease relapse after treatment, consisting of 11 locoregional recurrences and three distant metastases. The current study revealed the clinical outcomes of EBRT for EACC.
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http://dx.doi.org/10.3892/mco.2021.2207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818098PMC
March 2021

Reciprocal activation of HEY1 and NOTCH4 under SOX2 control promotes EMT in head and neck squamous cell carcinoma.

Int J Oncol 2021 02 10;58(2):226-237. Epub 2020 Dec 10.

Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.

Several comprehensive studies have demonstrated that the NOTCH pathway is altered in a bimodal manner in head and neck squamous cell carcinoma (HNSCC). In a previous study, it was found that the NOTCH4/HEY1 pathway was specifically upregulated in HNSCC and promoted epithelial‑mesenchymal transition (EMT), and that HEY1 activation supported SOX2 expression. However, the interactions in this pathway have not yet been fully elucidated. The present study investigated the NOTCH4/HEY1/SOX2 axis in HNSCC using in vitro models and the Cancer Genome Atlas (TCGA) database. To explore the association, reporter and ChIP RT‑qPCR assays using SOX2‑overexpressing (SOX2‑OE) cells were performed. The association between NOTCH4 and HEY1 was examined in the same manner using HEY1‑overexpressing (HEY1‑OE) cells. The results of the in vitro experiments indicated that HEY1 promoted EMT in the HNSCC cells. Furthermore, the overexpression of HEY1 also promoted sphere formation and increased murine xenograft tumorigenicity. Reporter assays and ChIP RT‑qPCR experiments indicated that SOX2 regulated HEY1 expression via direct binding of the HEY1 promoter. HEY1 expression significantly correlated with SOX2 expression in primary lung SCC and other SCCs using the TCGA database. HEY1 also regulated NOTCH4 expression to create a positive reciprocal feedback loop. On the whole, the present study demonstrates that HEY1 expression in HNSCC is regulated via the promotion of SOX2 and promotes EMT. The NOTCH4/HEY1 pathway is specifically upregulated via a positive reciprocal feedback loop mediated by the HEY1‑medaited regulation of NOTCH4 transcription, and SOX2 correlates with HEY1 expression in SCC from other primary sites.
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http://dx.doi.org/10.3892/ijo.2020.5156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864008PMC
February 2021

Interaction of Benzbromarone with Subdomains IIIA and IB/IIA on Human Serum Albumin as the Primary and Secondary Binding Regions.

Mol Pharm 2021 03 21;18(3):1061-1070. Epub 2021 Jan 21.

Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto 860-0082, Japan.

Benzbromarone has been used for the treatment of gout for more than 30 years. Although it shows a high level of binding to plasma proteins (>99%), our knowledge of this binding is not sufficiently extensive to permit us to understand its pharmacokinetics and pharmacodynamics. To address this issue in more detail, we characterized the binding of benzbromarone to human serum albumin (HSA), the most abundant protein in plasma. Equilibrium dialysis and circular dichroism findings indicated that benzbromarone binds strongly to one primary as well as to multiple secondary sites on HSA and that the bromine atoms of benzbromarone play important roles in this high affinity binding. An X-ray crystallographic study revealed that benzbromarone molecules bind to hydrophobic pockets within subdomains IB, IIA, and IIIA. Inhibition experiments using site specific ligands (subdomain IB; fusidic acid, IIA; warfarin, IIIA; diazepam) indicated that the primary and secondary binding sites that benzbromarone binds to are within subdomains IIIA and IB/IIA, respectively. Lastly, a study of the effect of fatty acids on the benzbromarone-HSA interaction suggested that benzbromarone, when displaced from subdomain IIIA by sodium oleate, could transfer to subdomains IB or IIA. Thus, these data will permit more relevant assessments of the displacement interactions of benzbromarone especially in cases of co-administered drugs or endogenous compounds that also bind to subdomain IIIA. In addition, the findings presented herein will also be useful for designing drug combination therapy in which pharmacokinetic and pharmacodynamic performance need to be controlled.
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http://dx.doi.org/10.1021/acs.molpharmaceut.0c01004DOI Listing
March 2021

Effects of unweighting on gait kinematics during walking on a lower-body positive-pressure treadmill in patients with hip osteoarthritis.

BMC Musculoskelet Disord 2021 Jan 8;22(1):46. Epub 2021 Jan 8.

Faculty of Health Sciences, Hokkaido University, Kita 12, Nishi 5, Kita-ku, Sapporo, 060-0812, Japan.

Background: Hip osteoarthritis (OA) is a musculoskeletal condition that makes walking difficult due to pain induced by weight-bearing activities. Treadmills that support the body weight (BW) reduce the load on the lower limbs, and those equipped with a lower-body positive-pressure (LBPP) device, developed as a new method for unweighting, significantly reduce pain in patients with knee OA. However, the effects of unweighting on gait kinematics remain unclear in patients with hip OA. Therefore, we investigated the effects of unweighting on kinematics in patients with hip OA during walking on a treadmill equipped with an LBPP device.

Methods: A total of 15 women with hip OA and 15 age-matched female controls wore a three-dimensional (3-D) motion analysis system and walked at a self-selected speed on the LBPP treadmill. Data regarding self-reported hip pain using a numeric rating scale (NRS) in which the scores 0 and 10 represented no pain and the worst pain, respectively, under three different BW conditions (100, 75, and 50%) were collected. Moreover, 3-D peak joint angles during gait under each condition were calculated and compared.

Results: In the hip OA group, the NRS pain scores at 50 and 75% BW conditions significantly decreased compared with that at 100% BW condition (50%, P = 0.002; 75%, P = 0.026), and the peak hip extension angle decreased compared with that in the healthy controls (P = 0.044). In both groups, unweighting significantly decreased the peak hip (P < 0.001) and knee (P < 0.001) flexion angles and increased the peak ankle plantar flexion angle (P < 0.001) during walking.

Conclusions: Unweighting by the LBPP treadmill decreased pain in the hip OA group but did not drastically alter the gait kinematics compared with that in the control group. Therefore, regarding the use of the LBPP treadmill for patients with hip OA, clinicians should consider the benefits of pain reduction rather than the kinematic changes.
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http://dx.doi.org/10.1186/s12891-020-03909-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792168PMC
January 2021

MRI findings of spring ligament injury: association with surgical findings and flatfoot deformity.

Acta Radiol Open 2020 Dec 14;9(12):2058460120980145. Epub 2020 Dec 14.

Department of Radiology, St. Marianna University School of Medicine, Kawasaki, Japan.

Background: Spring ligament injury is an important cause for flatfoot deformity; however, reliability of magnetic resonance imaging (MRI) findings of spring ligament injury is still ambiguous.

Purpose: To investigate the reliability of MRI findings for the diagnosis of spring ligament injury.

Material And Methods: Forty-three cases with spring ligament injury proven by surgery and 29 control cases were enrolled. The spring ligament complex was demonstrated on proton density-weighted images reconstructed from 3D-isotropic MRI data. The presence of waviness, discontinuity, and abnormally high signal intensity of the spring ligament complex was evaluated by two radiologists in cooperation. Also, injury of the posterior tibial tendon (PTT) on MRI and the lateral talo-1st metatarsal angles on weight-bearing X-rays were evaluated.

Results: Discontinuity and abnormally high signal intensity of the superomedial calcaneonavicular ligament (SmCNL) on MRI were more frequently observed in patients with spring ligament injury than in controls ( < 0.001). Discontinuity and abnormally high signal intensity of the SmCNL were found more often in the PTT injury group than in those without ( < 0.001). The talo-1st metatarsal angle was greater in patients with discontinuity and abnormally high signal intensity of the SmCNL on MRI than in patients without these findings ( < 0.001).

Conclusion: Discontinuity and abnormally high signal intensity are reliable MRI findings for spring ligament injury and related disorders, such as flatfoot deformity and PTT injury.
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http://dx.doi.org/10.1177/2058460120980145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739123PMC
December 2020

Effect of low-intensity pulsed ultrasound on injured temporomandibular joints with or without articular disc removal in a rabbit model.

J Dent Sci 2021 Jan 4;16(1):287-295. Epub 2020 May 4.

Department of Oral and Maxillofacial Surgery, Division of Clinical Medicine, Graduate Faculty of Interdisciplinary Research, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, Japan.

Background/purpose: Dynamic stimulation can induce bone and cartilage growth. The purpose of this study was to examine the effect of low-intensity pulsed ultrasound (LIPUS) on injured temporomandibular joints (TMJs) in a rabbit model.

Materials And Methods: Twenty-four female Japanese white rabbits (age: 12-16 weeks, weight: 2.0-2.5 kg) were equally divided into 4 groups. In two groups, discectomy was performed with (the LD group) and without (the D group) subsequent LIPUS treatment. In the other groups, a sham operation was performed with (the LC group) and without (the C group) subsequent LIPUS treatment. Two animals in each group were sacrificed at each time point (2, 4, and 8 weeks postoperatively). Mandibular measurements were made using three-dimensional computed tomography. We performed histological and immunohistochemical examination of the articular disc, and the cartilage layer and bone at the 30- and 60-degree sites in each condyle.

Results: There were no statistically significant differences among the groups in terms of thickness of the disc or the fibrous articular zone, or the number of BMP-2 positive cells. In terms of mandibular length, there were differences among the groups after 4 (P = 0.0498) and 8 weeks (P = 0.0260). Specifically, there was a difference between the LC group and the C group after 4 weeks (P = 0.014) and 8 weeks (P = 0.029).

Conclusions: This study suggests that LIPUS has little effect on cartilage after TMJ injury. It may promote bone growth in a normal TMJ, although discectomy seems to reduce this effect.
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http://dx.doi.org/10.1016/j.jds.2020.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770256PMC
January 2021
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