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Dive into the research topics where Koshi Kinoshita is active.

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Featured researches published by Koshi Kinoshita.


Nature Medicine | 2009

A rapid and efficient single-cell manipulation method for screening antigen-specific antibody-secreting cells from human peripheral blood.

Aishun Jin; Tatsuhiko Ozawa; Kazuto Tajiri; Tsutomu Obata; Sachiko Kondo; Koshi Kinoshita; Shinichi Kadowaki; Kazuo Takahashi; Toshiro Sugiyama; Hiroyuki Kishi; Atsushi Muraguchi

Antigen-specific human monoclonal antibodies (mAbs) are key candidates for therapeutic agents. However, the availability of a suitable screening system for antigen-specific antibody–secreting cells (ASCs) is limited in humans. Here we present a unique method for detecting individual ASCs using microwell array chips, which enables the analysis of live cells on a single-cell basis and offers a rapid, efficient and high-throughput (up to 234,000 individual cells) system for identifying and recovering objective ASCs. We applied the system to detect and retrieve ASCs for hepatitis B virus and influenza viruses from human peripheral blood lymphocytes and produced human mAbs with virus-neutralizing activities within a week. Furthermore, we show that the system is useful for detecting ASCs for multiple antigens as well as for selection of ASCs secreting high-affinity antibodies on a chip. Our method can open the way for the generation of therapeutic antibodies for individual patients.


Cytometry Part A | 2007

Cell-microarray analysis of antigen-specific B-cells: single cell analysis of antigen receptor expression and specificity.

Kazuto Tajiri; Hiroyuki Kishi; Yoshiharu Tokimitsu; Sachiko Kondo; Tatsuhiko Ozawa; Koshi Kinoshita; Aishun Jin; Shinichi Kadowaki; Toshiro Sugiyama; Atsushi Muraguchi

The authors previously developed a cell‐microarray system that effectively detects antigen‐specific B‐cells by monitoring intracellular Ca2+ at single cell levels. Here they present a novel method to detect antigen‐specific B‐cells using cell‐microarray system. To detect antigen‐specific B‐cells, they arrayed live lymphocytes on a chip, stained cells with fluorescence‐labeled nonspecific proteins, and analyzed them with a fluorescence scanner to detect nonspecific protein binding to B‐cells. They then stained cells with fluorescence‐labeled antigen and analyzed them with the scanner. Cells stained with specific antigen, but not with nonspecific proteins, were determined as antigen‐specific B‐cells and harvested. Antibody cDNA was amplified from retrieved B‐cells by single‐cell RT‐PCR, inserted into expression vectors, and was examined for its specificity by ELISA. They could detect antigen‐specific B‐cells at a frequency of 0.01% in a model system using transgenic mice that express antibody to hen‐egg lysozyme on the surface of B‐cells. They applied this system to directly detect hepatitis B virus surface‐antigen (HBs‐Ag)‐specific B‐cells from peripheral blood in HBs‐Ag‐vaccinated volunteers and succeeded in producing HBs‐Ag‐specific monoclonal antibody. This novel system allows us to identify human antigen‐specific B‐cells of very low frequency and is a powerful tool to explore the candidates of antibody therapeutics.


Heart Rhythm | 2016

Postmortem genetic analysis of sudden unexplained death syndrome under 50 years of age: A next-generation sequencing study

Yukiko Hata; Koshi Kinoshita; Koichi Mizumaki; Yoshiaki Yamaguchi; Keiichi Hirono; Fukiko Ichida; Asami Takasaki; Hisashi Mori; Naoki Nishida

BACKGROUND Recent studies on the genetic analysis of victims of sudden unexplained death syndrome (SUDS) have shown diagnostic potential. Previously, such analyses mainly targeted the major channelopathy-associated genes. OBJECTIVE The purpose of this study was to evaluate the utility of next-generation sequencing (NGS) in the postmortem diagnosis of SUDS. METHODS Our data are derived from 25 cases of SUDS (21 men and 4 women; age 19-50 years). A total of 70 genes were examined by NGS, and the pathogenicity of any detected rare variants with minor allele frequencies of <0.5% was evaluated using a widely used database and eight in silico algorithms. RESULTS Five known and 15 potentially pathogenic variants with a high in silico score were identified in 14 cases. In all, 6 channelopathy-related variants were identified in 5 cases, including 2 cases with history of arrhythmia; 11 cases had cardiomyopathy- or cardiac transcription factor-related variants. Three cases with desmosomal gene- or other cardiomyopathy-related variants showed possibly related pathologic changes. Three cases with RYR2 or TBX5 variants showed possible pathogenic fibrosis of the cardiac conduction system. Only 12 variants showed moderate or strong possible pathogenicity in SUDS cases compared with qualifying controls. CONCLUSION Hereditary heart diseases other than channelopathy may also be a significant cause of SUDS, even if clinical and pathologic findings do not show advanced disease. A combination of gene analysis using NGS and some predictive methods for detecting variants and careful pathologic evaluation may provide a reliable diagnosis of hereditary heart disease for potential SUDS cases.


Cytometry Part A | 2009

Identification of antigen‐specific B cells by concurrent monitoring of intracellular Ca2+ mobilization and antigen binding with microwell array chip system equipped with a CCD imager

Koshi Kinoshita; Tatsuhiko Ozawa; Kazuto Tajiri; Shinichi Kadowaki; Hiroyuki Kishi; Atsushi Muraguchi

B cells are very heterogeneous, consisting of more than 109 B‐cell clones with distinct specificities for antigens in each individual. To identify single B cells with antigen specificity, we have been developing cell microarray technology using microwell array chips whose microwells each capture a single B cell. Using microwell array chips, we detected antigen‐specific B cells by monitoring antigen‐induced intracellular Ca2+ mobilization with a CCD scanner (MAC‐CCD system) or the binding of fluorescence‐labeled antigen to cells with a confocal laser scanner. We retrieved target cells from the chip, cloned immunoglobulin genes, and produced antigen‐specific antibodies. However, these methods present some difficulties: the former technique could not detect cells whose frequency was less than 0.05% and the latter one took a long time to identify the objective cells although it could detect cells at a frequency of 0.01%. Here, we have combined the advantages of these two methods. Monitoring antigen‐induced intracellular Ca2+ mobilizations and the binding of fluorescence‐labeled antigens simultaneously with a MAC‐CCD system enabled us to detect rapidly, antigen‐specific B cells whose frequency was less than 0.01% with high efficiency. Our system provides a superior screening system for antigen‐specific B cells and extends the horizons of multiparameter single‐cell analysis in heterogeneous cell populations.


Brain Pathology | 2017

Epilepsy-Related Sudden Unexpected Death: Targeted Molecular Analysis of Inherited Heart Disease Genes using Next-Generation DNA Sequencing.

Yukiko Hata; Koji Yoshida; Koshi Kinoshita; Naoki Nishida

Inherited heart disease causing electric instability in the heart has been suggested to be a risk factor for sudden unexpected death in epilepsy (SUDEP). The purpose of this study was to reveal the correlation between epilepsy‐related sudden unexpected death (SUD) and inherited heart disease. Twelve epilepsy‐related SUD cases (seven males and five females, aged 11–78 years) were examined. Nine cases fulfilled the criteria of SUDEP, and three cases died by drowning. In addition to examining three major epilepsy‐related genes, we used next‐generation sequencing (NGS) to examine 73 inherited heart disease‐related genes. We detected both known pathogenic variants and rare variants with minor allele frequencies of <0.5%. The pathogenicity of these variants was evaluated and graded by eight in silico predictive algorithms. Six known and six potential rare variants were detected. Among these, three known variants of LDB3, DSC2 and KCNE1 and three potential rare variants of MYH6, DSP and DSG2 were predicted by in silico analysis as possibly highly pathogenic in three of the nine SUDEP cases. Two of three cases with desmosome‐related variants showed mild but possible significant right ventricular dysplasia‐like pathology. A case with LDB3 and MYH6 variants showed hypertrabeculation of the left ventricle and severe fibrosis of the cardiac conduction system. In the three drowning death cases, one case with mild prolonged QT interval had two variants in ANK2. This study shows that inherited heart disease may be a significant risk factor for SUD in some epilepsy cases, even if pathological findings of the heart had not progressed to an advanced stage of the disease. A combination of detailed pathological examination of the heart and gene analysis using NGS may be useful for evaluating arrhythmogenic potential of epilepsy‐related SUD.


Cardiovascular Pathology | 2015

Anomalous origin of the right coronary artery from the left coronary sinus with an intramural course: comparison between sudden-death and non-sudden-death cases

Yukiko Hata; Koshi Kinoshita; Keiko Kudo; Noriaki Ikeda; Naoki Nishida

BACKGROUND The prognosis of patients in whom the right coronary artery (RCA) arises from the left coronary sinus (LCS) is unequal. An initial intramural course of the coronary artery within the aortic media is considered to cause myocardial ischemia in cases of coronary anomalies. METHODS Clinicopathological findings in five autopsy cases where the RCA arose from the LCS with an intramural course were examined. Comparison between sudden cardiac death and noncardiac death was also performed. RESULTS Two of five cases were sudden cardiac death, and the other three cases were noncardiac death. In one case of sudden death, the person collapsed during light exercise, and in the other case, the person was under the effect of methamphetamine. Both of the cases of sudden death showed an RCA-dominant pattern in distribution of the coronary artery, atherosclerotic narrowing of the RCA, and acute ischemic necrosis in the posterior basilar ventricular septum around the atrioventricular conduction system, which is considered to be the territory of the RCA. CONCLUSIONS An intramural course within the aortic media may be an accelerating factor of decreased blood flow in cases with an origin of the RCA arising from the LCS because of compression from the aortic lumen. However, this finding may not be an independent predictor of pathological ischemia. Additional factors that diminish blood flow in the intramural segment may be required to cause significant myocardial ischemia. Additionally, inciting factors, which can increase blood pressure, may also play a role in causing symptomatic myocardial ischemia by initiating mechanical compression from the aorta to the intramural segment of the RCA.


Neuropathology and Applied Neurobiology | 2015

Pathological features of preclinical or early clinical stages of corticobasal degeneration: a comparison with advanced cases

Naoki Nishida; Koji Yoshida; Yukiko Hata; Yuichi Arai; Koshi Kinoshita

The manner in which pathological lesions of corticobasal degeneration (CBD) progress remains poorly understood. Because the pathology of early disease stages may be fundamental for elucidating a border between clinical and preclinical states of CBD, the present study aimed to detect preclinical or early clinical CBD cases by examining a series of forensic autopsy cases.


Journal of Cardiovascular Electrophysiology | 2012

A Novel Missense Mutation Causing a G487R Substitution in the S2–S3 Loop of Human ether‐à‐go‐go‐Related Gene Channel

Koshi Kinoshita; Yoshiaki Yamaguchi; B E Kohki Nishide; B E Katsuya Kimoto; B E Yuki Nonobe; B E Akira Fujita; B E Kenta Asano; Toshihide Tabata; Hisashi Mori; Hiroshi Inoue; Yukiko Hata; Kenkichi Fukurotani; Naoki Nishida

hERG(G487R) Channel. Introduction: Mutations of human ether‐à‐go‐go‐related gene (hERG), which encodes a cardiac K+ channel responsible for the acceleration of the repolarizing phase of an action potential and the prevention of premature action potential regeneration, often cause severe arrhythmic disorders. We found a novel missense mutation of hERG that results in a G487R substitution in the S2–S3 loop of the channel subunit [hERG(G487R)] from a family and determined whether this mutant gene could induce an abnormality in channel function.


Pediatric Research | 2016

MicroRNA-93 may control vascular endothelial growth factor A in circulating peripheral blood mononuclear cells in acute Kawasaki disease.

Kazuyoshi Saito; Hideyuki Nakaoka; Ichiro Takasaki; Keiichi Hirono; Seiji Yamamoto; Koshi Kinoshita; Nariaki Miyao; Keijiro Ibuki; Sayaka Ozawa; Kazuhiro Watanabe; Neil E. Bowles; Fukiko Ichida

Background:Kawasaki disease (KD) is the most common systemic vasculitis syndrome primarily affecting medium-sized arteries, particularly the coronary arteries. Though KD may be associated with immunological problems, the involvement of microRNAs (miRs) has not been fully described.Methods:We enrolled 23 KD patients and 12 controls. We performed miR and mRNA microarray analysis of peripheral blood mononuclear cells (PBMCs) isolated from acute KD patients and controls. Continuously, we measured specific miRs, mRNA and the expression of proteins by using reverse-transcriptase PCR (RT-PCR) and enzyme-linked immunosorbent assay (ELISA).Results:We identified strikingly high levels of miR-182 and miR-296-5p during the acute febrile phase, and of miR-93, miR-145-5p, miR-145-3p, and miR-150-3p in the defervescence stage, especially in refractory KD patients. The expression of vascular endothelial growth factor A (VEGFA) mRNA, previously reported to be controlled by miR-93, was significantly elevated during the febrile phase and normalized upon treatment, negatively correlating with the expression of miR-93. Further, plasma levels of VEGF-A correlated with PBMC VEGFA mRNA expression.Conclusion:Several miRs are highly specific to the acute phase of KD, and may participate in regulating the expression of genes in pathways associated with KD. In particular, miR-93 may participate in regulating expression of VEGF-A and contribute to the pathogenesis of arteritis in acute KD.


Journal of Neuropathology and Experimental Neurology | 2015

Neuropathologic features of suicide victims who presented with acute poststroke depression: significance of association with neurodegenerative disorders.

Naoki Nishida; Yukiko Hata; Koji Yoshida; Koshi Kinoshita

Abstract To investigate the neuropathologic characteristics of poststroke depression (PSD) leading to suicide, we retrospectively selected deceased subjects who had been diagnosed as having early PSD. Cases were divided into subjects who had committed suicide and those who had not. Neuropathologic examinations, including immunohistochemistry, were conducted. Twenty-four subjects fulfilled criteria for early PSD; 11 of these had committed suicide, and the other 13 had not. Lesion type, size of stroke, and location of stroke were variable but did not differ significantly between the groups. Alzheimer disease–related pathology stages also did not differ between the groups. Argyrophilic grain disease was found in both the suicide group (6 of 11) and the nonsuicide group (2 of 13); there were 2 highly possible cases of early progressive supranuclear palsy in the suicide group. Together, argyrophilic grain disease and progressive supranuclear palsy were found significantly more frequently in suicide cases than in nonsuicide cases (p = 0.01). These data suggest that overlapping 4-repeat tauopathies, which include argyrophilic grain disease and progressive supranuclear palsy, might be an important aggravating factor of PSD that could lead to suicide. The presence of other neurodegenerative diseases does not preclude PSD because the prevalence of these diseases in older persons suggests that they might often occur concomitantly.

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