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Article: Potential marker subset of blood-circulating cytokines on hematopoietic progenitor-to-Th1 pathway in COVID-19.

Takashima, Yasuo / Inaba, Tohru / Matsuyama, Tasuku / Yoshii, Kengo / Tanaka, Masami / Matsumoto, Kazumichi / Sudo, Kazuki / Tokuda, Yuichi / Omi, Natsue / Nakano, Masakazu / Nakaya, Takaaki / Fujita, Naohisa / Sotozono, Chie / Sawa, Teiji / Tashiro, Kei / Ohta, Bon

Frontiers in medicine

2024 Volume 11, Page(s) 1319980

Abstract: In this study, we analyzed a relatively large subset of proteins, including 109 kinds of blood-circulating cytokines, and precisely described a cytokine storm in the expression level and the range of fluctuations during hospitalization for COVID-19. Of ... ...

Abstract	In this study, we analyzed a relatively large subset of proteins, including 109 kinds of blood-circulating cytokines, and precisely described a cytokine storm in the expression level and the range of fluctuations during hospitalization for COVID-19. Of the proteins analyzed in COVID-19, approximately 70% were detected with Bonferroni-corrected significant differences in comparison with disease severity, clinical outcome, long-term hospitalization, and disease progression and recovery. Specifically, IP-10, sTNF-R1, sTNF-R2, sCD30, sCD163, HGF, SCYB16, IL-16, MIG, SDF-1, and fractalkine were found to be major components of the COVID-19 cytokine storm. Moreover, the 11 cytokines (i.e., SDF-1, SCYB16, sCD30, IL-11, IL-18, IL-8, IFN-γ, TNF-α, sTNF-R2, M-CSF, and I-309) were associated with the infection, mortality, disease progression and recovery, and long-term hospitalization. Increased expression of these cytokines could be explained in sequential pathways from hematopoietic progenitor cell differentiation to Th1-derived hyperinflammation in COVID-19, which might also develop a novel strategy for COVID-19 therapy with recombinant interleukins and anti-chemokine drugs.
Language	English
Publishing date	2024-02-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2024.1319980
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Article ; Online: Novel Vertical Cup-to-Disc Classification to Identify Normal Eyes That Maintain Non-Glaucoma Status: A 10-Year Longitudinal Study.

Ikeda, Yoko / Mori, Kazuhiko / Maruyama, Yuko / Ueno, Morio / Yoshii, Kengo / Yamamoto, Yuji / Imai, Kojiro / Omi, Natsue / Sato, Ryuichi / Sato, Fumiko / Nakano, Masakazu / Hamuro, Junji / Tashiro, Kei / Sotozono, Chie / Kinoshita, Shigeru

Journal of glaucoma

2022 Volume 32, Issue 2, Page(s) 127–132

Abstract: Prcis: We propose a new classification model to serve as a control for future genomic studies of glaucoma by distinguishing normal subjects maintaining non-glaucoma status for 10 years using the vertical cup-to-disc ratio (VCDR).: Purpose: This study ...

Abstract	Prcis: We propose a new classification model to serve as a control for future genomic studies of glaucoma by distinguishing normal subjects maintaining non-glaucoma status for 10 years using the vertical cup-to-disc ratio (VCDR). Purpose: This study aimed to develop a classification for distinguishing subjects maintaining non-glaucoma status for 10 years using the VCDR. Participants and methods: Among 842 volunteers 40 years and older, 421 volunteers participated in the second ophthalmic examination 10 years after their first examination. Each volunteer was diagnosed either as healthy normal or glaucoma suspect (GS) in the first glaucoma screening examinations. The former was further classified into the 3 grades of N1, N2, and N3. Specifically, N1 represented (1) VCDR <0.3; (2) no notching or nerve fiber layer defect; and (3) no undermining, N2 indicated 0.3≤VCDR<0.6 and conditions (2) and (3) of N1; and N3 represented 0.3≤VCDR<0.6 with undermining and condition (2), or 0.6≤VCDR<0.7 and condition (2) of N1. Glaucoma transition rates (GTRs) were evaluated in 421 volunteers who returned to participate after a 10-year period. Results: GTRs were calculated as 1.3% in both N1 and N2, 3.9% in N3, and 18.2% in GS. The ratio of volunteers in the same category maintenance rate increased from N1 to N3. Conclusion: GTRs were lower in N1 and N2 than in N3 or GS during the 10-year study period. This novel classification of healthy non-glaucoma subjects may help identify those, especially Japanese males, who maintain a non-glaucoma status for an extended period of 10 years.
MeSH term(s)	Male ; Humans ; Optic Disk ; Longitudinal Studies ; Intraocular Pressure ; Glaucoma/diagnosis ; Ocular Hypertension/diagnosis
Language	English
Publishing date	2022-08-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	913494-3
ISSN	1536-481X ; 1057-0829
ISSN (online)	1536-481X
ISSN	1057-0829
DOI	10.1097/IJG.0000000000002109
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Article ; Online: Seasonal Variation and Trend of Intraocular Pressure Decrease Over a 20-Year Period in Normal-Tension Glaucoma Patients.

Ikeda, Yoko / Mori, Kazuhiko / Ueno, Morio / Yoshii, Kengo / Nakano, Masakazu / Sato, Ryuichi / Sato, Fumiko / Maruyama, Yuko / Imai, Kojiro / Omi, Natsue / Yamamoto, Yuji / Yamasaki, Toshihide / Tashiro, Kei / Sotozono, Chie / Kinoshita, Shigeru

American journal of ophthalmology

2021 Volume 234, Page(s) 235–240

Abstract: Purpose: To investigate the trend of seasonal variation of intraocular pressure (IOP) in patients with normal-tension glaucoma over a 20-year period by retrospectively analyzing the Kyoto Prefectural University of Medicine Glaucoma Registry database as ... ...

Abstract	Purpose: To investigate the trend of seasonal variation of intraocular pressure (IOP) in patients with normal-tension glaucoma over a 20-year period by retrospectively analyzing the Kyoto Prefectural University of Medicine Glaucoma Registry database as real-world data. Design: Retrospective cohort study. Methods: Data points (n = 49,007) were extracted retrospectively from the medical records of 1774 patients with normal-tension glaucoma (665 male patients and 1109 female patients; mean ± SD age was 59.8 ± 14.4 years; and mean ± SD observation period was 5.6 ± 4.4 years) seen over the 20-year period. We first calculated the mean IOP from all available data of each month from January 1997 through December 2016. The data were then categorized into 5 groups of 4 consecutive years each (1997-2000, 2001-2004, 2005-2008, 2009-2012, and 2013-2016) and the mean IOP of each month within the group was calculated. Seasonal variations of IOP over the 20-year study period and in the 5 consecutive groups were then investigated via nonlinear multiple regression analysis. Results: A continuous decrease of IOP was detected throughout the 20-year period (P < .001), with distinct seasonal variation. The annual mean ± SD IOP was highest (13.9 ± 2.7 mm Hg) in the oldest group (1997-2000), with a gradual decrease in each subsequent group, finally becoming lowest (12.3 ± 2.7 mm Hg) in the most recent group (2013-2016) (P < .001), and all of them were accompanied by distinct seasonal variation (P < .001). Conclusions: Based on the Kyoto Prefectural University of Medicine Glaucoma Registry real-world longitudinal data, our findings revealed a continuous decrease and distinct seasonal variation of IOP in patients with normal-tension glaucoma throughout the 20-year study period.
MeSH term(s)	Aged ; Female ; Glaucoma ; Humans ; Intraocular Pressure ; Male ; Middle Aged ; Retrospective Studies ; Seasons ; Tonometry, Ocular
Language	English
Publishing date	2021-10-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	80030-2
ISSN	1879-1891 ; 0002-9394
ISSN (online)	1879-1891
ISSN	0002-9394
DOI	10.1016/j.ajo.2021.10.001
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Article: Adult-onset leukoencephalopathy with homozygous

Yasuda, Rei / Yoshida, Tomokatsu / Mizuta, Ikuko / Watanabe, Masashi / Nakano, Masakazu / Sato, Ryuichi / Tokuda, Yuichi / Omi, Natsue / Sakai, Norio / Nakagawa, Masanori / Tashiro, Kei / Mizuno, Toshiki

Neurology. Genetics

2020 Volume 6, Issue 4, Page(s) e442

Language	English
Publishing date	2020-05-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	2818607-2
ISSN	2376-7839
ISSN	2376-7839
DOI	10.1212/NXG.0000000000000442
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Article ; Online: Efficient and reliable establishment of lymphoblastoid cell lines by Epstein-Barr virus transformation from a limited amount of peripheral blood.

Omi, Natsue / Tokuda, Yuichi / Ikeda, Yoko / Ueno, Morio / Mori, Kazuhiko / Sotozono, Chie / Kinoshita, Shigeru / Nakano, Masakazu / Tashiro, Kei

Scientific reports

2017 Volume 7, Page(s) 43833

Abstract: Lymphoblastoid cell lines (LCLs) transformed by Epstein-Barr virus (EBV) serve as an unlimited resource of human genomic DNA. The protocol that is widely used to establish LCLs involves peripheral blood mononuclear cell isolation by density gradient ... ...

Abstract	Lymphoblastoid cell lines (LCLs) transformed by Epstein-Barr virus (EBV) serve as an unlimited resource of human genomic DNA. The protocol that is widely used to establish LCLs involves peripheral blood mononuclear cell isolation by density gradient centrifugation, however, that method requires as much as 5 ml of peripheral blood. In this study, in order to provide a more simple and efficient method for the generation of LCLs, we developed a new protocol using hemolytic reaction to enrich white blood cells for EBV transformation and found that the hemolytic protocol successfully generated LCLs from a small volume (i.e., 0.1 ml) of peripheral blood. To assess the quality of genomic DNA extracted from LCLs established by the hemolytic protocol (LCL-hemolytic), we performed single nucleotide polymorphism (SNP) microarray genotyping using the GeneChip
MeSH term(s)	Cell Line, Transformed ; Genome, Human/genetics ; Genotype ; Herpesvirus 4, Human/physiology ; Humans ; Leukocytes/cytology ; Leukocytes/metabolism ; Leukocytes/virology ; Leukocytes, Mononuclear/cytology ; Leukocytes, Mononuclear/metabolism ; Leukocytes, Mononuclear/virology ; Lymphocytes/metabolism ; Lymphocytes/virology ; Oligonucleotide Array Sequence Analysis ; Polymorphism, Single Nucleotide ; Reproducibility of Results
Language	English
Publishing date	2017-03-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/srep43833
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Article ; Online: Novel common variants and susceptible haplotype for exfoliation glaucoma specific to Asian population.

Nakano, Masakazu / Ikeda, Yoko / Tokuda, Yuichi / Fuwa, Masahiro / Ueno, Morio / Imai, Kojiro / Sato, Ryuichi / Omi, Natsue / Adachi, Hiroko / Kageyama, Masaaki / Mori, Kazuhiko / Kinoshita, Shigeru / Tashiro, Kei

Scientific reports

2014 Volume 4, Page(s) 5340

Abstract: The common variants in lysyl oxidase-like 1 gene (LOXL1) are associated with exfoliation glaucoma (XFG) patients developed through exfoliation syndrome (XFS). However, the risk allele of a variant in LOXL1 has been found to be inverted between Asian and ... ...

Abstract	The common variants in lysyl oxidase-like 1 gene (LOXL1) are associated with exfoliation glaucoma (XFG) patients developed through exfoliation syndrome (XFS). However, the risk allele of a variant in LOXL1 has been found to be inverted between Asian and Caucasian populations. Therefore, we newly performed a genome-wide association study using 201 XFS/XFG and 697 controls in Japanese, and identified 34 genome-wide significant single-nucleotide polymorphisms (SNPs) distributing in not only LOXL1 but also TBC1D21 and PML at the 15q24.1 locus. These SNPs were confirmed by an independent population consisted of 121 XFS/XFG and 263 controls in Japanese. Moreover, further analyses revealed a unique haplotype structure only from the combination of TBC1D21 and LOXL1 variants showing a high XFS/XFG susceptibility specific for the Asian population. Although there still should be other gene(s) in the other region(s) contributing to the disease process, these results suggested that the combination of newly discovered variants in these genes might be useful for precise XFG risk assessment, as well as for elucidating the molecular mechanism of XFG pathogenesis through XFS.
MeSH term(s)	Aged ; Aged, 80 and over ; Amino Acid Oxidoreductases/genetics ; Asian Continental Ancestry Group/genetics ; Exfoliation Syndrome/ethnology ; Exfoliation Syndrome/genetics ; Female ; GTPase-Activating Proteins/genetics ; Gene Frequency ; Genetic Predisposition to Disease/ethnology ; Genetic Predisposition to Disease/genetics ; Genome-Wide Association Study/methods ; Genome-Wide Association Study/statistics & numerical data ; Haplotypes ; Humans ; Japan ; Male ; Meta-Analysis as Topic ; Middle Aged ; Nuclear Proteins/genetics ; Polymorphism, Single Nucleotide ; Promyelocytic Leukemia Protein ; Risk Factors ; Transcription Factors/genetics ; Tumor Suppressor Proteins/genetics
Chemical Substances	GTPase-Activating Proteins ; Nuclear Proteins ; Promyelocytic Leukemia Protein ; TBC1D21 protein, human ; Transcription Factors ; Tumor Suppressor Proteins ; PML protein, human (143220-95-5) ; Amino Acid Oxidoreductases (EC 1.4.-) ; LOXL1 protein, human (EC 1.4.3.-)
Language	English
Publishing date	2014-06-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/srep05340
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Article: Syndactyly and preaxial synpolydactyly in the single Sfrp2 deleted mutant mice.

Ikegawa, Masaya / Han, Hua / Okamoto, Akihiko / Matsui, Ryosuke / Tanaka, Masami / Omi, Natsue / Miyamae, Mahito / Toguchida, Junya / Tashiro, Kei

Developmental dynamics : an official publication of the American Association of Anatomists

2008 Volume 237, Issue 9, Page(s) 2506–2517

Abstract: Secreted Frizzled-related protein 2 (Sfrp2) or Stromal Cell Derived Factor-5 (SDF-5) is highly expressed in the developing limbs. Here we showed the single Sfrp2 inactivation in mice resulted in syndactyly and preaxial synpolydactyly, predominantly in ... ...

Abstract	Secreted Frizzled-related protein 2 (Sfrp2) or Stromal Cell Derived Factor-5 (SDF-5) is highly expressed in the developing limbs. Here we showed the single Sfrp2 inactivation in mice resulted in syndactyly and preaxial synpolydactyly, predominantly in the hindlimbs. Tails were often kinked. A penetrance of the syndactyly was highest in 129/SvJ or CBA/N x 129/SvJ background and the phenotype was haploinsufficient. Preaxial synpolydactyly was seen in homozygous mutants in C57BL/6 x 129/SvJ. Of note, syndactyly showed retarded apoptosis of the second and the third interdigital spaces; concomitantly, mesodermal Msx2 expression was down-regulated. Impaired digital anlagen maturation was also noticeable in the same position. Preaxial synpolydactyly of the Sfrp2 mutants was a non-mirror image type and Shh independent. Although joint formation was not disrupted, chondrocyte maturation was preaxially disturbed. Our results suggest that the Sfrp2 deleted mice can be a useful animal model to study human syndactyly/preaxial synpolydactyly defects.
MeSH term(s)	Animals ; Apoptosis/genetics ; Apoptosis/physiology ; Chondrogenesis/genetics ; Chondrogenesis/physiology ; Gene Expression Regulation, Developmental ; In Situ Hybridization ; Limb Deformities, Congenital/genetics ; Limb Deformities, Congenital/pathology ; Membrane Proteins/genetics ; Membrane Proteins/physiology ; Mice ; Mice, Mutant Strains ; Polydactyly/genetics ; Polydactyly/pathology ; Syndactyly/genetics ; Syndactyly/pathology
Chemical Substances	Membrane Proteins ; Sfrp2 protein, mouse
Language	English
Publishing date	2008-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	1102541-4
ISSN	1097-0177 ; 1058-8388
ISSN (online)	1097-0177
ISSN	1058-8388
DOI	10.1002/dvdy.21655
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Article ; Online: Common variants in CDKN2B-AS1 associated with optic-nerve vulnerability of glaucoma identified by genome-wide association studies in Japanese.

Nakano, Masakazu / Ikeda, Yoko / Tokuda, Yuichi / Fuwa, Masahiro / Omi, Natsue / Ueno, Morio / Imai, Kojiro / Adachi, Hiroko / Kageyama, Masaaki / Mori, Kazuhiko / Kinoshita, Shigeru / Tashiro, Kei

PloS one

2012 Volume 7, Issue 3, Page(s) e33389

Abstract: Background: To date, only a small portion of the genetic variation for primary open-angle glaucoma (POAG), the major type of glaucoma, has been elucidated.: Methods and principal findings: We examined our two data sets of the genome-wide association ... ...

Abstract	Background: To date, only a small portion of the genetic variation for primary open-angle glaucoma (POAG), the major type of glaucoma, has been elucidated. Methods and principal findings: We examined our two data sets of the genome-wide association studies (GWAS) derived from a total of 2,219 Japanese subjects. First, we performed a GWAS by analyzing 653,519 autosomal common single-nucleotide polymorphisms (SNPs) in 833 POAG patients and 686 controls. As a result, five variants that passed the Bonferroni correction were identified in CDKN2B-AS1 on chromosome 9p21.3, which was already reported to be a significant locus in the Caucasian population. Moreover, we combined the data set with our previous GWAS data set derived from 411 POAG patients and 289 controls by the Mantel-Haenszel test, and all of the combined variants showed stronger association with POAG (P<5.8 × 10(-10)). We then subdivided the case groups into two subtypes based on the value of intraocular pressure (IOP)--POAG with high IOP (high pressure glaucoma, HPG) and that with normal IOP (normal pressure glaucoma, NPG)--and performed the GWAS using the two data sets, as the prevalence of NPG in Japanese is much higher than in Caucasians. The results suggested that the variants from the same CDKN2B-AS1 locus were likely to be significant for NPG patients. Conclusions and significance: In this study, we successfully identified POAG-associated variants in the CDKN2B-AS1 locus using a Japanese population, i.e., variants originally reported as being associated with the Caucasian population. Although we cannot rule out that the significance could be due to the differences in sample size between HPG and NPG, the variants could be associated specifically with the vulnerability of the optic nerve to IOP, which is useful for investigating the etiology of glaucoma.
MeSH term(s)	Asian Continental Ancestry Group ; Case-Control Studies ; Chromosomes, Human, Pair 9/genetics ; Genetic Predisposition to Disease/genetics ; Genome-Wide Association Study ; Genotype ; Glaucoma/epidemiology ; Glaucoma/genetics ; Glaucoma/pathology ; Humans ; Intraocular Pressure/genetics ; Intraocular Pressure/physiology ; Japan/epidemiology ; Optic Nerve/pathology ; Polymorphism, Single Nucleotide/genetics ; Prevalence ; RNA, Long Noncoding ; RNA, Untranslated/genetics
Chemical Substances	CDKN2B antisense RNA, human ; RNA, Long Noncoding ; RNA, Untranslated
Keywords	covid19
Language	English
Publishing date	2012-03-12
Publishing country	United States
Document type	Journal Article
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0033389
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Article: An approach to predict the risk of glaucoma development by integrating different attribute data.

Tokuda, Yuichi / Yagi, Tomohito / Yoshii, Kengo / Ikeda, Yoko / Fuwa, Masahiro / Ueno, Morio / Nakano, Masakazu / Omi, Natsue / Tanaka, Masami / Mori, Kazuhiko / Kageyama, Masaaki / Nagasaki, Ikumitsu / Yagi, Katsumi / Kinoshita, Shigeru / Tashiro, Kei

SpringerPlus

2012 Volume 1, Page(s) 41

Abstract: Primary open-angle glaucoma (POAG) is one of the major causes of blindness worldwide and considered to be influenced by inherited and environmental factors. Recently, we demonstrated a genome-wide association study for the susceptibility to POAG by ... ...

Abstract	Primary open-angle glaucoma (POAG) is one of the major causes of blindness worldwide and considered to be influenced by inherited and environmental factors. Recently, we demonstrated a genome-wide association study for the susceptibility to POAG by comparing patients and controls. In addition, the serum cytokine levels, which are affected by environmental and postnatal factors, could be also obtained in patients as well as in controls, simultaneously. Here, in order to predict the effective diagnosis of POAG, we developed an "integration approach" using different attribute data which were integrated simply with several machine learning methods and random sampling. Two data sets were prepared for this study. The one is the "training data set", which consisted of 42 POAG and 42 controls. The other is the "test data set" consisted of 73 POAG and 52 controls. We first examined for genotype and cytokine data using the training data set with general machine learning methods. After the integration approach was applied, we obtained the stable accuracy, using the support vector machine method with the radial basis function. Although our approach was based on well-known machine learning methods and a simple process, we demonstrated that the integration with two kinds of attributes, genotype and cytokines, was effective and helpful in diagnostic prediction of POAG.
Language	English
Publishing date	2012-10-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2661116-8
ISSN	2193-1801
ISSN	2193-1801
DOI	10.1186/2193-1801-1-41
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Article: Genetic analysis of Nakano Cataract and its modifier genes in mice.

Narita, Makiko / Wang, Yun / Kita, Akiyo / Omi, Natsue / Yamada, Yoshihiro / Hiai, Hiroshi

Experimental eye research

2002 Volume 75, Issue 6, Page(s) 745–751

Abstract: The Nakano Cataract (NCT) is an autosomal, recessive, single gene mutation in mice leading to an osmotic cataract induced by an endogenous inhibitor of Na, K-ATPase. In this report, we further refined the map position of the mutant locus to a <0.7c M ... ...

Abstract	The Nakano Cataract (NCT) is an autosomal, recessive, single gene mutation in mice leading to an osmotic cataract induced by an endogenous inhibitor of Na, K-ATPase. In this report, we further refined the map position of the mutant locus to a <0.7c M segment between D16Mit5 and D16Mit185 in 1,000 BALB/c-nct/nct x(BALB/c- nct/nctxMSM)F1 backcrossed mice with PCR-based microsatellite analysis. The NCT in the original Nakano mice developed at 3 weeks of age, rapidly formed a pin-head type dense opacity, whereas the cataract in the congenic BALB/c- nct/nct mice developed at 5-6 weeks of age or later, slowly formed a diffuse opacity. A major histological difference was the presence or absence of heavy condensation of the lens nucleus. These two types of cataract were segregated in the backcrossed mice. Linkage analysis of the two subtypes among the backcrossed mice revealed two recessive BALB/c-derived modifier genes on chromosome 3 and 10.
MeSH term(s)	Animals ; Cataract/genetics ; Cataract/metabolism ; Cataract/pathology ; Chromosome Mapping ; Crosses, Genetic ; Crystallins/analysis ; Disease Models, Animal ; Electrophoresis, Polyacrylamide Gel ; Genes, Recessive ; Genetic Linkage ; Haplotypes ; Mice ; Mice, Inbred BALB C ; Microsatellite Repeats ; Mutation
Chemical Substances	Crystallins
Language	English
Publishing date	2002-12-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80122-7
ISSN	1096-0007 ; 0014-4835
ISSN (online)	1096-0007
ISSN	0014-4835
DOI	10.1006/exer.2002.2068
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