Publications by authors named "Hiroshi Kawasaki"

184 Publications

Visual cortex damage in a ferret model of ocular hypertension.

Jpn J Ophthalmol 2022 Jan 19. Epub 2022 Jan 19.

Department of Ophthalmology, University of Tokyo School of Medicine, 7-3-1 Hongo Bunkyoku, Tokyo, 113-8655, Japan.

Purpose: We aimed to analyze the changes in the visual cortex of a ferret model of ocular hypertension (OH) using cytochrome oxidase (CO) staining.

Study Design: Experimental.

Methods: OH was induced in 9 ferrets by means of injection of cultured conjunctival cells into the anterior chamber of the right eye. Three ferrets were used as the controls. CO staining was performed to assess the metabolic intensity at the II-III and IVC layers of the visual cortex.

Results: The intensities of CO staining in the right and left II-III layers of the primary visual cortex (V1) in the OH ferrets were 39.8 ± 10.3 and 41.9 ± 9.2 arbitrary units, respectively. In the control ferrets, the intensity was 88.1 ± 8.1 arbitrary units. The intensity of CO staining of the II-III layers obtained from the OH eyes was significantly lower than that from the control eyes (unpaired t test, P < .01). The intensities of CO staining in the right and left IVC layers of V1 in the OH ferrets were 60.3 ± 12.8 and 60.0 ± 13.5 arbitrary units, respectively. In the control ferrets, the intensity was 111.4 ± 9.6 arbitrary units. The CO staining intensity of the IVC layer obtained from the OH eyes was significantly lower than that from the control eyes (unpaired t test, P < .01).

Conclusion: The CO staining intensity was reduced in the visual cortex from OH eyes. This study revealed that OH causes metabolic change in the visual cortex.
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http://dx.doi.org/10.1007/s10384-022-00901-8DOI Listing
January 2022

Highly Precise, Continuous, Long-term Monitoring of Skin Electrical Resistance by Nanomesh Electrodes.

Adv Healthc Mater 2022 Jan 6:e2102425. Epub 2022 Jan 6.

Department of Electrical Engineering and Information Systems, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.

The transepidermal water loss has been widely used as a method for directly evaluating the barrier function of the stratum corneum of the skin. However, transepidermal water loss could not be measured continuously for a long period of time, and there were no reports of continuous monitoring of skin barrier functions. Here, we report a method to continuously monitor the skin electrical resistance by nanomesh electrodes for a long period of time while maintaining the natural skin condition that does not inhibit water evaporation. Simultaneous measurements of the skin electrical resistance by nanomesh electrodes and transepidermal water loss exhibited a linear fit with a high negative correlation. Furthermore, dynamics of skin physiological functions have been successfully visualized by monitoring of the skin electrical resistance by nanomesh electrodes for 30 h in daily life. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/adhm.202102425DOI Listing
January 2022

Active Stereo Method for 3D Endoscopes using Deep-layer GCN and Graph Representation with Proximity Information.

Annu Int Conf IEEE Eng Med Biol Soc 2021 11;2021:7551-7555

Techniques for 3D endoscopic systems have been widely studied for various reasons. Among them, active stereo based systems, in which structured-light patterns are projected to surfaces and endoscopic images of the pattern are analyzed to produce 3D depth images, are promising, because of robustness and simple system configurations. For those systems, finding correspondences between a projected pattern and an original pattern is an open problem. Recently, correspondence estimation by graph neural networks (GCN) using graph-based representation of the patterns were proposed for 3D endoscopic systems. One severe problem of the approach is that the graph matching by GCN is largely affected by the stability of the graph construction process using the detected patterns of a captured image. If the detected pattern is fragmented into small pieces, graph matching may fail and 3D shapes cannot be retrieved. In this paper, we propose a solution for those problems by applying deep-layered GCN and extended graph representations of the patterns, where proximity information is added. Experiments show that the proposed method outperformed the previous method in accuracies for correspondence matching for 3D reconstruction.
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http://dx.doi.org/10.1109/EMBC46164.2021.9629696DOI Listing
November 2021

Stratification of atopic dermatitis patients by patterns of response to proactive therapy with topical tacrolimus: low serum IgE levels and inadequately controlled disease activity at the start of treatment predict its failure.

Ann Med 2021 12;53(1):2205-2214

Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.

Purpose: Topical calcineurin inhibitors (TCIs) are an important anti-inflammatory drug for treating atopic dermatitis (AD). However, those treatment responses are variable. In this study, we stratified AD patients by patterns of response to remission maintenance therapy (proactive therapy) with topical tacrolimus, a typical TCI. Thereafter, we explored patient features that predict the success or failure of proactive therapy using TCI (TCI proactive therapy).

Methods: A single-arm open-label clinical study aimed to evaluate the efficacy of TCI proactive therapy was conducted in 31 patients with AD. Patients were treated with TCS to induce remission (remission-induction period) followed by daily TCI ointment (0.1% tacrolimus) application for 4 weeks (maintenance therapy period), and twice-weekly application for 12 weeks (proactive therapy period). Based on its results, treatment outcomes were correlated with the patients' clinical and laboratory findings.

Results: Of the 31 patients enrolled in the study, 21 successfully completed maintenance therapy (TCI responders). Among them, 13 completed (proactive-completed group) and 8 failed proactive therapy (proactive-dropout group). At the beginning of maintenance therapy, the serum IgE level was significantly higher in the TCI responders than in those who failed maintenance therapy ( = 0.049). At the beginning of proactive therapy, the mean-SCORing Atopic Dermatitis (SCORAD) score was significantly different between the proactive-completed (11.7 ± 4.6) and proactive-dropout (16.6 ± 4.2) groups ( = 0.025). In proactive-dropout group patients, worsened disease activity correlated well with the elevation of serum lactate dehydrogenase (LDH) and Thymus and activation-regulated chemokine (TARC) levels and peripheral eosinophil count.

Conclusion: AD patients were stratified into three different response patterns to TCI proactive therapy. Patients with less involvement of IgE in the pathogenesis and inadequate remission induction by TCS may not be expected to respond well to TCI proactive therapy.Key messagesAD patients can be stratified into three types according to their pattern of responsiveness to TCI proactive therapy.The efficacy of TCI proactive therapy is lower in AD patients with lower serum IgE levels.TCI proactive therapy should be done after the achievement of adequate remission induction by TCS.
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http://dx.doi.org/10.1080/07853890.2021.2004319DOI Listing
December 2021

ERAD components Derlin-1 and Derlin-2 are essential for postnatal brain development and motor function.

iScience 2021 Jul 19;24(7):102758. Epub 2021 Jun 19.

Laboratory of Biochemistry and Molecular Biology, Department of Medical Sciences, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.

Derlin family members (Derlins) are primarily known as components of the endoplasmic reticulum-associated degradation pathway that eliminates misfolded proteins. Here we report a function of Derlins in the brain development. Deletion of or in the central nervous system of mice impaired postnatal brain development, particularly of the cerebellum and striatum, and induced motor control deficits. Derlin-1 or Derlin-2 deficiency reduced neurite outgrowth and and surprisingly also inhibited sterol regulatory element binding protein 2 (SREBP-2)-mediated brain cholesterol biosynthesis. In addition, reduced neurite outgrowth due to Derlin-1 deficiency was rescued by SREBP-2 pathway activation. Overall, our findings demonstrate that Derlins sustain brain cholesterol biosynthesis, which is essential for appropriate postnatal brain development and function.
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http://dx.doi.org/10.1016/j.isci.2021.102758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324814PMC
July 2021

The distribution of Cdh20 mRNA demarcates somatotopic subregions and subpopulations of spiny projection neurons in the rat dorsolateral striatum.

J Comp Neurol 2021 11 16;529(16):3655-3675. Epub 2021 Jul 16.

Jichi Medical University, Shimotsuke, Tochigi, Japan.

The dorsolateral striatum (DLS) of rodents is functionally subdivided into somatotopic subregions that represent each body part along both the dorsoventral and anteroposterior (A-P) axes and play crucial roles in sensorimotor functions via corticostriatal pathways. However, little is known about the spatial gene expression patterns and heterogeneity of spiny projection neurons (SPNs) within somatotopic subregions. Here, we show that the cell adhesion molecule gene Cdh20, which encodes a Type II cadherin, is expressed in discrete subregions covering the inner orofacial area and part of the forelimb area in the ventral domain of the DLS (v-DLS) in rats. Cdh20-expressing cells were localized in the v-DLS at the intermediate level of the striatum along the A-P axis and could be classified as direct-pathway SPNs or indirect-pathway SPNs. Unexpectedly, comprehensive analysis revealed that Cdh20 is expressed in SPNs in the rat DLS but not in the mouse DLS or the ferret putamen (Pu). Our observations reveal that Cdh20 expression demarcates somatotopic subregions and subpopulations of SPNs specifically in the rat DLS and suggest divergent regulation of genes differentially expressed in the v-DLS and Pu among mammals.
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http://dx.doi.org/10.1002/cne.25215DOI Listing
November 2021

Establishment of an induced pluripotent stem cell line from a female domestic ferret (Mustela putorius furo) with an X chromosome instability.

Stem Cell Res 2021 05 11;53:102385. Epub 2021 May 11.

Department of Physiology, Keio University School of Medicine, Tokyo, Japan; Laboratory for Marmoset Neural Architecture, RIKEN Center for Brain Science, Saitama, Japan. Electronic address:

The domestic ferret (ferret; Mustela putorius furo) is an important animal model for neuroscience and preclinical/veterinary medicine owing to its highly developed cerebral cortex and susceptibility to avian influenza and corona viruses. Nevertheless, there is a lack of in vitro ferret models, since immortal cell lines including induced pluripotent stem cells (iPSCs) of ferrets have been scarce. In this study, we established an iPSC line from ferret skin fibroblasts. The established iPSC line, fiPS-1, showed standard characteristics of pluripotency, but its X chromosome was unstable. Collectively, the present study provides a useful resource for in vitro model using the ferret.
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http://dx.doi.org/10.1016/j.scr.2021.102385DOI Listing
May 2021

BMP signaling alters aquaporin-4 expression in the mouse cerebral cortex.

Sci Rep 2021 05 18;11(1):10540. Epub 2021 May 18.

Department of Medical Neuroscience, Graduate School of Medical Sciences, Kanazawa University, Takara-machi 13-1, Kanazawa, Ishikawa, 920-8640, Japan.

Aquaporin-4 (AQP4) is a predominant water channel expressed in astrocytes in the mammalian brain. AQP4 is crucial for the regulation of homeostatic water movement across the blood-brain barrier (BBB). Although the molecular mechanisms regulating AQP4 levels in the cerebral cortex under pathological conditions have been intensively investigated, those under normal physiological conditions are not fully understood. Here we demonstrate that AQP4 is selectively expressed in astrocytes in the mouse cerebral cortex during development. BMP signaling was preferentially activated in AQP4-positive astrocytes. Furthermore, activation of BMP signaling by in utero electroporation markedly increased AQP4 levels in the cerebral cortex, and inhibition of BMP signaling strongly suppressed them. These results indicate that BMP signaling alters AQP4 levels in the mouse cerebral cortex during development.
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http://dx.doi.org/10.1038/s41598-021-89997-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131757PMC
May 2021

Staphylococcus cohnii is a potentially biotherapeutic skin commensal alleviating skin inflammation.

Cell Rep 2021 04;35(4):109052

Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo 160-8582, Japan; JSR-Keio University Medical and Chemical Innovation Center, Keio University School of Medicine, Tokyo 160-8582, Japan; Center for Integrative Medical Science (IMS), RIKEN, Kanagawa 230-0045, Japan. Electronic address:

Host-microbe interactions orchestrate skin homeostasis, the dysregulation of which has been implicated in chronic inflammatory conditions such as atopic dermatitis and psoriasis. Here, we show that Staphylococcus cohnii is a skin commensal capable of beneficially inhibiting skin inflammation. We find that Tmem79 mice spontaneously develop interleukin-17 (IL-17)-producing T-cell-driven skin inflammation. Comparative skin microbiome analysis reveals that the disease activity index is negatively associated with S. cohnii. Inoculation with S. cohnii strains isolated from either mouse or human skin microbiota significantly prevents and ameliorates dermatitis in Tmem79 mice without affecting pathobiont burden. S. cohnii colonization is accompanied by activation of host glucocorticoid-related pathways and induction of anti-inflammatory genes in the skin and is therefore effective at suppressing inflammation in diverse pathobiont-independent dermatitis models, including chemically induced, type 17, and type 2 immune-driven models. As such, S. cohnii strains have great potential as effective live biotherapeutics for skin inflammation.
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http://dx.doi.org/10.1016/j.celrep.2021.109052DOI Listing
April 2021

Phosphorylation of GAP-43 T172 is a molecular marker of growing axons in a wide range of mammals including primates.

Mol Brain 2021 04 8;14(1):66. Epub 2021 Apr 8.

Departments of Neurochemistry and Molecular Cell Biology, School of Medicine and Graduate School of Medical/Dental Sciences, Niigata University, Niigata, 951-8510, Japan.

GAP-43 is a vertebrate neuron-specific protein and that is strongly related to axon growth and regeneration; thus, this protein has been utilized as a classical molecular marker of these events and growth cones. Although GAP-43 was biochemically characterized more than a quarter century ago, how this protein is related to these events is still not clear. Recently, we identified many phosphorylation sites in the growth cone membrane proteins of rodent brains. Two phosphorylation sites of GAP-43, S96 and T172, were found within the top 10 hit sites among all proteins. S96 has already been characterized (Kawasaki et al., 2018), and here, phosphorylation of T172 was characterized. In vitro (cultured neurons) and in vivo, an antibody specific to phosphorylated T172 (pT172 antibody) specifically recognized cultured growth cones and growing axons in developing mouse neurons, respectively. Immunoblotting showed that pT172 antigens were more rapidly downregulated throughout development than those of pS96 antibody. From the primary structure, this phosphorylation site was predicted to be conserved in a wide range of animals including primates. In the developing marmoset brainstem and in differentiated neurons derived from human induced pluripotent stem cells, immunoreactivity with pT172 antibody revealed patterns similar to those in mice. pT172 antibody also labeled regenerating axons following sciatic nerve injury. Taken together, the T172 residue is widely conserved in a wide range of mammals including primates, and pT172 is a new candidate molecular marker for growing axons.
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http://dx.doi.org/10.1186/s13041-021-00755-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034164PMC
April 2021

Streptococcus pyogenes upregulates arginine catabolism to exert its pathogenesis on the skin surface.

Cell Rep 2021 03;34(13):108924

Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, Suita, Osaka 565-0871, Japan. Electronic address:

The arginine deiminase (ADI) pathway has been found in many kinds of bacteria and functions to supplement energy production and provide protection against acid stress. The Streptococcus pyogenes ADI pathway is upregulated upon exposure to various environmental stresses, including glucose starvation. However, there are several unclear points about the advantages to the organism for upregulating arginine catabolism. We show that the ADI pathway contributes to bacterial viability and pathogenesis under low-glucose conditions. S. pyogenes changes global gene expression, including upregulation of virulence genes, by catabolizing arginine. In a murine model of epicutaneous infection, S. pyogenes uses the ADI pathway to augment its pathogenicity by increasing the expression of virulence genes, including those encoding the exotoxins. We also find that arginine from stratum-corneum-derived filaggrin is a key substrate for the ADI pathway. In summary, arginine is a nutrient source that promotes the pathogenicity of S. pyogenes on the skin.
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http://dx.doi.org/10.1016/j.celrep.2021.108924DOI Listing
March 2021

The expression of aristaless-related homeobox in neural progenitors of gyrencephalic carnivore ferrets.

Biochem Biophys Rep 2021 Jul 6;26:100970. Epub 2021 Mar 6.

Department of Medical Neuroscience, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, 920-8640, Japan.

Aristaless-related homeobox (ARX) has important functions in the development of various organs including the brain. Mutations of the human gene have been associated with malformations of the cerebral cortex such as microcephaly and lissencephaly. Although the expression patterns of ARX in the lissencephalic cerebral cortex of mice have been intensively investigated, those in expanded gyrencephalic brains remained unclear. Here, we show the expression patterns of ARX in the developing cerebral cortex of gyrencephalic carnivore ferrets. We found that ARX was expressed not only in intermediate progenitor (IP) cells but also in outer radial glial (oRG) cells, which are neural progenitors preferentially observed in the gyrencephalic cerebral cortex. We found that the majority of ARX-positive oRG cells expressed the proliferating cell marker Ki-67. These results may indicate that ARX in oRG cells mediates the expansion of the gyrencephalic cerebral cortex during development and evolution.
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http://dx.doi.org/10.1016/j.bbrep.2021.100970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941032PMC
July 2021

Glial cell type-specific gene expression in the mouse cerebrum using the piggyBac system and in utero electroporation.

Sci Rep 2021 03 1;11(1):4864. Epub 2021 Mar 1.

Department of Medical Neuroscience, Graduate School of Medical Sciences, Kanazawa University, Takara-machi 13-1, Kanazawa, Ishikawa, 920-8640, Japan.

Glial cells such as astrocytes and oligodendrocytes play crucial roles in the central nervous system. To investigate the molecular mechanisms underlying the development and the biological functions of glial cells, simple and rapid techniques for glial cell-specific genetic manipulation in the mouse cerebrum would be valuable. Here we uncovered that the Gfa2 promoter is suitable for selective gene expression in astrocytes when used with the piggyBac system and in utero electroporation. In contrast, the Blbp promoter, which has been used to induce astrocyte-specific gene expression in transgenic mice, did not result in astrocyte-specific gene expression. We also identified the Plp1 and Mbp promoters could be used with the piggyBac system and in utero electroporation to induce selective gene expression in oligodendrocytes. Furthermore, using our technique, neuron-astrocyte or neuron-oligodendrocyte interactions can be visualized by labeling neurons, astrocytes and oligodendrocytes differentially. Our study provides a fundamental basis for specific transgene expression in astrocytes and/or oligodendrocytes in the mouse cerebrum.
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http://dx.doi.org/10.1038/s41598-021-84210-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921133PMC
March 2021

[Investigation of the Mechanisms Underlying Development and Diseases of the Cerebral Cortex Using Mice and Ferrets].

Authors:
Hiroshi Kawasaki

Yakugaku Zasshi 2021 ;141(3):349-357

Department of Medical Neuroscience, Graduate School of Medicine, Kanazawa University.

Folds of the cerebral cortex, which are called gyri and sulci, are one of the most prominent features of the mammalian brain. However, the mechanisms underlying the development and malformation of cortical folds are largely unknown, mainly because they are difficult to investigate in mice, whose brain do not have cortical folds. To investigate the mechanisms underlying the development and malformation of cortical folds, we developed a genetic manipulation technique for the cerebral cortex of gyrencephalic carnivore ferrets. Genes-of-interest can be expressed in the ferret cortex rapidly and efficiently. We also demonstrated that genes-of-interest can be knocked out in the ferret cortex by combining in utero electroporation and the CRISPR/Cas9 system. Using our technique, we found that fibroblast growth factor (FGF) signaling and sonic hedgehog (Shh) signaling are crucial for cortical folding. In addition, we found that FGF signaling and Shh signaling preferentially increased outer radial glial cells and the thickness of upper layers of the cerebral cortex. Furthermore, over-activation of FGF signaling and Shh signaling resulted in polymicrogyria. Our findings provide in vivo data about the mechanisms of cortical folding in gyrencephalic mammals. Our technique for the ferret cerebral cortex should be useful for investigating the mechanisms underlying the development and diseases of the cerebral cortex that cannot be investigated using mice.
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http://dx.doi.org/10.1248/yakushi.20-00198-3DOI Listing
June 2021

Usefulness of the gracilis muscle flap for reconstruction of large perineal defects following total pelvic exenteration with sacrectomy.

ANZ J Surg 2021 09 6;91(9):1932-1934. Epub 2021 Jan 6.

Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.

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http://dx.doi.org/10.1111/ans.16566DOI Listing
September 2021

Assessment of skin barrier function using skin images with topological data analysis.

NPJ Syst Biol Appl 2020 12 18;6(1):40. Epub 2020 Dec 18.

Medical Sciences Innovation Hub Program, RIKEN, Yokohama, Kanagawa, 230-0045, Japan.

Recent developments of molecular biology have revealed diverse mechanisms of skin diseases, and precision medicine considering these mechanisms requires the frequent objective evaluation of skin phenotypes. Transepidermal water loss (TEWL) is commonly used for evaluating skin barrier function; however, direct measurement of TEWL is time-consuming and is not convenient for daily clinical practice. Here, we propose a new skin barrier assessment method using skin images with topological data analysis (TDA). TDA enabled efficient identification of structural features from a skin image taken by a microscope. These features reflected the regularity of the skin texture. We found a significant correlation between the topological features and TEWL. Moreover, using the features as input, we trained machine-learning models to predict TEWL and obtained good accuracy (R = 0.524). Our results suggest that assessment of skin barrier function by topological image analysis is promising.
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http://dx.doi.org/10.1038/s41540-020-00160-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749164PMC
December 2020

Single nucleotide variations in genes associated with innate immunity are enriched in Japanese adult cases of face and neck type atopic dermatitis.

J Dermatol Sci 2021 Feb 19;101(2):93-100. Epub 2020 Nov 19.

Center for Supercentenarian Medical Research, Keio University School of Medicine, Tokyo, Japan. Electronic address:

Background: Atopic dermatitis (AD) is heterogenous in terms of phenotype as well as genetic and environmental factors, while its associated genetic factors and pathophysiology are not fully understood.

Objective: We identify novel genetic factors enriched in a subgroup of AD patients with characteristic clinical features.

Methods: We clinically subgrouped 18 AD patients who exhibited distinctive characteristic of persistent skin eruption areas on the face and neck from 92 Japanese adult AD patients and identified disease-associated genetic factors enriched within the subgroup. Targeted resequencing and subsequent genetic association analyses were used to identify novel enriched genetic variations in the subgroup compared with the other AD patients.

Results: Targeted resequencing of 648 skin associated genes revealed an enrichment of 12 single nucleotide variations (SNVs) in patients with face and neck AD (n = 18) compared with the general Japanese population in the database. Subsequent allele frequency comparison between the face and neck AD and non - face and neck AD subgroups revealed enrichment of five SNVs. Multivariate analysis using genotype data revealed that three SNVs in theTLR1, TIRAP, and PSAPL1 genes, two of the three genes are involved in the Toll-like receptor pathway, were significantly enriched in patients with face and neck AD.

Conclusion: These findings revealed that the SNVs in genes associated with the innate immune pathway are enriched in a subgroup of AD. The combinational approach of clinical subgrouping and genotyping is valuable for detecting novel disease-associated genetic factors.
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http://dx.doi.org/10.1016/j.jdermsci.2020.11.005DOI Listing
February 2021

Fully Auto-calibrated Active-stereo-based 3D Endoscopic System using Correspondence Estimation with Graph Convolutional Network.

Annu Int Conf IEEE Eng Med Biol Soc 2020 07;2020:4357-4360

We have developed a series of 3D endoscopic systems where a micro-sized pattern projector is inserted through the instrument channel of the endoscope and shapes are reconstructed by a structured light technique using captured images of the endoscopic camera. One problem of the previous works is that the accuracy of shape reconstruction is low, because the projector cannot be fixed to the endoscope, and thus, the pose of the pattern projector w.r.t. the camera cannot be pre-calibrated. In this paper, we propose a method to auto-calibrate the pose of the projector without using any special devices nor manual process. Since the technique is one-shot, multiple shapes can be reconstructed from an image sequence and a large 3D scene can be recovered by merging them. Experiments are conducted using the real system.
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http://dx.doi.org/10.1109/EMBC44109.2020.9176417DOI Listing
July 2020

PPG3D: Does 3D head tracking improve camera-based PPG estimation?

Annu Int Conf IEEE Eng Med Biol Soc 2020 07;2020:1194-1197

Over the last few years, camera-based estimation of vital signs referred to as imaging photoplethysmography (iPPG) has garnered significant attention due to the relative simplicity, ease, unobtrusiveness and flexibility offered by such measurements. It is expected that iPPG may be integrated into a host of emerging applications in areas as diverse as autonomous cars, neonatal monitoring, and telemedicine. In spite of this potential, the primary challenge of non-contact camera-based measurements is the relative motion between the camera and the subjects. Current techniques employ 2D feature tracking to reduce the effect of subject and camera motion but they are limited to handling translational and in-plane motion. In this paper, we study, for the first-time, the utility of 3D face tracking to allow iPPG to retain robust performance even in presence of out-of-plane and large relative motions. We use a RGB-D camera to obtain 3D information from the subjects and use the spatial and depth information to fit a 3D face model and track the model over the video frames. This allows us to estimate correspondence over the entire video with pixel-level accuracy, even in the presence of out-of-plane or large motions. We then estimate iPPG from the warped video data that ensures per-pixel correspondence over the entire window-length used for estimation. Our experiments demonstrate improvement in robustness when head motion is large.
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http://dx.doi.org/10.1109/EMBC44109.2020.9176065DOI Listing
July 2020

An anatomical review of various superior mesenteric artery-first approaches during pancreatoduodenectomy for pancreatic cancer.

Surg Today 2021 Jun 22;51(6):872-879. Epub 2020 Sep 22.

Department of Gastrointestinal Surgery, Ibaraki Prefectural Central Hospital, Koibuchi 6528, Kasama, Ibaraki, 309-1793, Japan.

When pancreatic head cancer invades the superior mesenteric artery (SMA), attempts at curative resection are aborted. Preoperative imaging diagnostics to determine the surgical curability have yet to surpass the intraoperative information acquired via inspection, palpation, and trial dissection. Pancreatoduodenectomy (PD) is a standard measure for treating periampullary cancers. In conventional PD, SMA invasion is usually identified by dissecting the retroportal lamina, which connects the uncinate process and SMA nerve plexus after dividing the neck of the pancreas. During PD for pancreatic head cancer, this retroperitoneal margin frequently vitiates surgical curability. SMA-first approaches during PD are methods where the SMA is dissected first by severing the posterior pancreatic capsule to assess the SMA involvement of pancreatic cancer early in the operation. The first report of such an approach prompted subsequent reports of various maneuvers that are now known collectively as "artery-first" approaches. We herein review those approaches by classifying them according to (1) the side of the mesocolon from where the SMA approach occurs (supracolic or infracolic) and (2) the direction of access (right or left and anterior or posterior). The steps of the reported PD procedures are numbered according to a timeline and summarized using anatomical division of the SMA.
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http://dx.doi.org/10.1007/s00595-020-02150-zDOI Listing
June 2021

Exploration of biomarkers to predict clinical improvement of atopic dermatitis in patients treated with dupilumab: A study protocol.

Medicine (Baltimore) 2020 Sep;99(38):e22043

Department of Dermatology, Osaka Habikino Medical Center, Habikino City, Osaka.

Background: Atopic dermatitis (AD) is a common eczematous skin disorder that profoundly reduces the quality of life due to intractable pruritus. Excellent therapeutic success of the anti-interleukin 4 receptor-α antibody dupilumab in clinical trials and a real-world clinical context indicates the crucial roles of interleukin (IL)-4 and IL-13 in the pathogenesis of AD. Along with the clinical improvement in skin scores and pruritus, dupilumab significantly and progressively reduces and normalizes the upregulated expression of T helper type 2 signatures such as Chemokine (C-C motif) ligand (CCL)17, CCL18, CCL22, and CCL26 in the lesional skin of AD. However, no blood/serum biomarkers are known to predict good or poor outcome in patients with AD treated with dupilumab.

Methods: Patients are at least 18 years of age and have moderate-to-severe AD with Eczema Area and Severity Index (EASI) ≥16, Investigator's Global Assessment ≥3, and body surface area ≥10%. We are going to enroll more than 130 subjects from 18 medical facilities. Clinical objective findings will be evaluated by EASI. Subjective symptoms will be assessed by Patient-Oriented Eczema Measure, Numerical Rating Scale for Pruritus (Pruritus-NRS), Skin Comfort-NRS, and Treatment Satisfaction-NRS. We will measure 18 blood/serum biomarkers including % eosinophils in blood cell count, lactate dehydrogenase, total IgE, soluble interleukin 2 receptor, CCL17, CCL18, CCL22, CCL26, CCL27, IL-13, IL-22, IL-24, IL-25, IL-31, IL-33, thymic stromal lymphopoietin, periostin, and squamous cell carcinoma antigen-2. The clinical evaluation and biomarker sampling will be performed at 0, 2, 4, 8, and 16 weeks of dupilumab treatment. We will also perform proteomic analysis (of roughly 300 proteins) of the patients' sera obtained at 0 and 2 weeks of treatment. The primary endpoint is the association between "baseline levels of 18 biomarkers" and "% change from baseline of EASI at 16 weeks of dupilumab treatment."

Discussion: This is the first clinical trial to explore the biomarkers, including potential proteomic markers, most strongly associated with improvement in EASI in patients with moderate-to-severe AD treated with dupilumab for 16 weeks (B-PAD study). A limitation is that we will only enroll Japanese patients.
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http://dx.doi.org/10.1097/MD.0000000000022043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505282PMC
September 2020

Visualization of the Retina in Intact Eyes of Mice and Ferrets Using a Tissue Clearing Method.

Transl Vis Sci Technol 2020 02 7;9(3). Epub 2020 Feb 7.

Department of Medical Neuroscience, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, Japan.

Purpose: Visualization of specific cells and structures in intact organs would greatly facilitate our knowledge about pathological changes; therefore, a tissue clearing method applicable to the intact eye may be valuable. Here we report a novel imaging method for the retina using the hyperhydration-based tissue clearing technique CUBIC (Clear, Unobstructed Brain/Body Imaging Cocktails and Computational Analysis).

Methods: Eyes of Institute of Cancer Research (ICR) mice, C57BL/6 mice, and normally pigmented sable ferrets () were used. Intact eyes were subjected to CUBIC, melanin bleaching with HO, and immunostaining. Images of the retina in intact eyes were taken using epifluorescence microscopes and confocal microscopes.

Results: The combination of melanin bleaching and CUBIC efficiently made the eyes of C57BL/6 mice transparent. By combining melanin bleaching, CUBIC, and immunostaining, we succeeded in visualization of retinal structures from the outside of the intact eyes of mice. Furthermore, we found that our methods were applicable not only to mouse eyes but also to ferret eyes, which are much larger than those of mice.

Conclusions: Our method was useful for visualizing specific cells and structures in the retina of intact eyes with single-cell resolution without making tissue sections.

Translational Relevance: This simple and efficient method can be applicable to various rodent models, including those associated with glaucoma or myopia, and will facilitate evaluating the effects of novel therapy for relevant eye diseases by visualizing changes from the retina to the sclera at both molecular and macroscopic levels simultaneously in a whole-eye preparation.
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http://dx.doi.org/10.1167/tvst.9.3.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347279PMC
February 2020

In Vivo Targeting of Neural Progenitor Cells in Ferret Neocortex by In Utero Electroporation.

J Vis Exp 2020 05 6(159). Epub 2020 May 6.

Max Planck Institute of Molecular Cell Biology and Genetics;

Manipulation of gene expression in vivo during embryonic development is the method of choice when analyzing the role of individual genes during mammalian development. In utero electroporation is a key technique for the manipulation of gene expression in the embryonic mammalian brain in vivo. A protocol for in utero electroporation of the embryonic neocortex of ferrets, a small carnivore, is presented here. The ferret is increasingly being used as a model for neocortex development, because its neocortex exhibits a series of anatomical, histological, cellular, and molecular features that are also present in human and nonhuman primates, but absent in rodent models, such as mouse or rat. In utero electroporation was performed at embryonic day (E) 33, a midneurogenesis stage in ferret. In utero electroporation targets neural progenitor cells lining the lateral ventricles of the brain. During neurogenesis, these progenitor cells give rise to all other neural cell types. This work shows representative results and analyses at E37, postnatal day (P) 1, and P16, corresponding to 4, 9, and 24 days after in utero electroporation, respectively. At earlier stages, the progeny of targeted cells consists mainly of various neural progenitor subtypes, whereas at later stages most labeled cells are postmitotic neurons. Thus, in utero electroporation enables the study of the effect of genetic manipulation on the cellular and molecular features of various types of neural cells. Through its effect on various cell populations, in utero electroporation can also be used for the manipulation of histological and anatomical features of the ferret neocortex. Importantly, all these effects are acute and are performed with a spatiotemporal specificity determined by the user.
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http://dx.doi.org/10.3791/61171DOI Listing
May 2020

A novel third mesh-like myometrial layer connects the longitudinal and circular muscle fibers -A potential stratum to coordinate uterine contractions.

Sci Rep 2020 05 19;10(1):8274. Epub 2020 May 19.

Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.

Periodic myometrial contraction is one of the important uterine functions to achieve embryo implantation and parturition. Although it is well-known that the mammalian myometrium is composed of longitudinal (outer) and circular (inner) layers, the precise mechanisms that coordinate both muscular contractions to produce peristaltic movements remain unclear. Recently, by treatment with our modified Clear Unobstructed Brain Imaging Cocktails and Computational analysis (CUBIC) tissue-clearing method, we obtained well-contrasted three-dimensional images of the transparent murine ovary using enhanced green fluorescent protein (EGFP) transgenic mice and light-sheet microscopy. Consequently, to investigate accurate anatomical connections between outer and inner myometrial fibers, we observed whole structures of the myometrium using a transparent murine uterus. By this method, we identified a novel muscle layer, a middle layer of the myometrium, which anatomically connects the conventional outer longitudinal and inner circular muscles. This new layer was visualized as a mesh-like structure and this structure was observed throughout the whole uterus from proximal to distal sites. In this area, CD31-positive vessels were abundantly localized around the mesh-like muscle fibers. In addition, CD34-positive uterine telocytes and tubulin β-3-positive nerve fibers were closely located in this middle layer. These findings indicate the presence of a novel mesh-like stratum that connects longitudinal and circular muscle layers, and suggest its coordinating role in myometrial contractions.
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http://dx.doi.org/10.1038/s41598-020-65299-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237439PMC
May 2020

A discrete subtype of neural progenitor crucial for cortical folding in the gyrencephalic mammalian brain.

Elife 2020 04 21;9. Epub 2020 Apr 21.

Department of Medical Neuroscience, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.

An increase in the diversity of neural progenitor subtypes and folding of the cerebral cortex are characteristic features which appeared during the evolution of the mammalian brain. Here, we show that the expansion of a specific subtype of neural progenitor is crucial for cortical folding. We found that outer radial glial (oRG) cells can be subdivided by HOPX expression in the gyrencephalic cerebral cortex of ferrets. Compared with HOPX-negative oRG cells, HOPX-positive oRG cells had high self-renewal activity and were accumulated in prospective gyral regions. Using our in vivo genetic manipulation technique for ferrets, we found that the number of HOPX-positive oRG cells and their self-renewal activity were regulated by sonic hedgehog (Shh) signaling. Importantly, suppressing Shh signaling reduced HOPX-positive oRG cells and cortical folding, while enhancing it had opposing effects. Our results reveal a novel subtype of neural progenitor important for cortical folding in gyrencephalic mammalian cerebral cortex.
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http://dx.doi.org/10.7554/eLife.54873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173966PMC
April 2020

Profiling of taste-related compounds during the fermentation of Japanese sake brewed with or without a traditional seed mash (kimoto).

J Biosci Bioeng 2020 Jul 4;130(1):63-70. Epub 2020 Apr 4.

Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address:

Japanese sake production involves three processes: rice koji fermentation, seed mash fermentation, and main mash fermentation. Traditional seed mash (kimoto) production utilizes natural lactic acid produced by lactic acid bacteria for pure cultures of only sake yeast, preventing the growth of wild yeast and other unwanted bacteria. Recently, because kimoto production requires substantial time and labor, sake yeast mass-cultured in usual liquid medium has been used as a seed mash alternative. Sake quality is highly similar to that of kimoto, suggesting that they share similar component profiles. However, comparative component analyses of sake brewed with kimoto and sake brewed with cultured yeast are lacking. In this study, a time-course analysis of hydrophilic compounds in the main mash brewed with kimoto and with cultured yeast as well as a sensory evaluation of the products were performed. As a result, differences in various compounds and in umami taste level between sake brewed with kimoto and cultured yeast were detected. This is the first comparative analysis of changes in the component profile during sake main mash brewing using kimoto seed mash and cultured sake yeast; our results clarify the effects of kimoto seed mash on main mash brewing and sake quality.
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http://dx.doi.org/10.1016/j.jbiosc.2020.02.017DOI Listing
July 2020

The origin and development of subcortical U-fibers in gyrencephalic ferrets.

Mol Brain 2020 03 10;13(1):37. Epub 2020 Mar 10.

Department of Medical Neuroscience, Graduate School of Medical Sciences, Kanazawa University, Takara-machi 13-1, Kanazawa, Ishikawa, 920-8640, Japan.

In the white matter of the human cerebrum, the majority of cortico-cortical fibers are of short range, connecting neighboring cortical areas. U-fibers represent connections between neighboring areas and are located in the white matter immediately deep to the cerebral cortex. Using gyrencephalic carnivore ferrets, here we investigated the neurochemical, anatomical and developmental features of U-fibers. We demonstrate that U-fibers were derived from neighboring cortical areas in ferrets. U-fiber regions in ferrets were intensely stained with Gallyas myelin staining and Turnbull blue iron staining. We further found that U-fibers were derived from neurons in both upper and lower layers in neighboring areas of the cerebral cortex and that U-fibers were formed later than axons in the deep white matter during development. Our findings shed light on the fundamental features of U-fibers in the gyrencephalic cerebral cortex. Because genetic manipulation techniques for ferrets are now available, ferrets should be an important option for investigating the development, functions and pathophysiological changes of U-fibers.
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http://dx.doi.org/10.1186/s13041-020-00575-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063767PMC
March 2020

Structural Changes and Astrocyte Response of the Lateral Geniculate Nucleus in a Ferret Model of Ocular Hypertension.

Int J Mol Sci 2020 Feb 17;21(4). Epub 2020 Feb 17.

Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo 113-8655, Japan.

We investigated structural changes and astrocyte responses of the lateral geniculate nucleus (LGN) in a ferret model of ocular hypertension (OH). In 10 ferrets, OH was induced via the injection of cultured conjunctival cells into the anterior chamber of the right eye; six normal ferrets were used as controls. Anterograde axonal tracing with cholera toxin B revealed that atrophic damage was evident in the LGN layers receiving projections from OH eyes. Immunohistochemical analysis with antibodies against NeuN, glial fibrillary acidic protein (GFAP), and Iba-1 was performed to specifically label neurons, astrocytes, and microglia in the LGN. Significantly decreased NeuN immunoreactivity and increased GFAP and Iba-1 immunoreactivities were observed in the LGN layers receiving projections from OH eyes. Interestingly, the changes in the immunoreactivities were significantly different among the LGN layers. The C layers showed more severe damage than the A and A1 layers. Secondary degenerative changes in the LGN were also observed, including neuronal damage and astrocyte reactions in each LGN layer. These results suggest that our ferret model of OH is valuable for investigating damages during the retina-brain transmission of the visual pathway in glaucoma. The vulnerability of the C layers was revealed for the first time.
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http://dx.doi.org/10.3390/ijms21041339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072923PMC
February 2020

Simultaneous shape and camera-projector parameter estimation for 3D endoscopic system using CNN-based grid-oneshot scan.

Healthc Technol Lett 2019 Dec 26;6(6):249-254. Epub 2019 Nov 26.

Graduate School and Faculty of Information Science and Electrical Engineering, Kyushu University, Fukuoka, Japan.

For effective in situ endoscopic diagnosis and treatment, measurement of polyp sizes is important. For this purpose, 3D endoscopic systems have been researched. Among such systems, an active stereo technique, which projects a special pattern wherein each feature is coded, is a promising approach because of simplicity and high precision. However, previous works of this approach have problems. First, the quality of 3D reconstruction depended on the stabilities of feature extraction from the images captured by the endoscope camera. Second, due to the limited pattern projection area, the reconstructed region was relatively small. In this Letter, the authors propose a learning-based technique using convolutional neural networks to solve the first problem and an extended bundle adjustment technique, which integrates multiple shapes into a consistent single shape, to address the second. The effectiveness of the proposed techniques compared to previous techniques was evaluated experimentally.
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http://dx.doi.org/10.1049/htl.2019.0070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943237PMC
December 2019

Mass-forming hepatic cryptococcosis: a mimicker of metastatic tumors.

Abdom Radiol (NY) 2020 07;45(7):2268-2273

Department of Radiology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.

This report provides the first imaging report of isolated intrahepatic cryptococcosis. An 83-year-old man was incidentally pointed out of hepatic nodules. CT revealed four well-defined nodules of 21 mm, 15 mm, 7 mm, and 5 mm in diameter without contrast enhancement. Two nodules displayed central hyperattenuation and the others were totally hyperattenuating. MRI showed that the nodules were hypointense relative to normal liver parenchyma on T1- and T2-weighted images. 18F-FDG PET imaging revealed no obvious increased uptake of nuclear species into the liver nodules. Partial resection of the three largest hepatic nodules was performed based on a preoperative diagnosis of hepatic metastasis from known sigmoid colon cancer. All three resected nodules were composed mainly of necrotic tissue with peripheral histiocytic aggregates and numerous yeast-like cells. The final diagnosis was hepatic cryptococcosis.
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http://dx.doi.org/10.1007/s00261-020-02437-2DOI Listing
July 2020
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