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Article ; Online: Characterization of fish-specific IFNγ-related binding with a unique receptor complex and signaling through a novel pathway.

Shibasaki, Yasuhiro / Yabu, Takeshi / Shiba, Hajime / Moritomo, Tadaaki / Mano, Nobuhiro / Nakanishi, Teruyuki

2024 Volume 14, Issue 4, Page(s) 532–544

Abstract: Unlike mammals, fish express two type II interferons, IFNγ and fish-specific IFNγ (IFNγ-related or IFNγrel). We previously reported the presence of two IFNγrel genes, IFNγrel 1 and IFNγrel 2, which exhibit potent antiviral activity in the Ginbuna crucian ...

Abstract	Unlike mammals, fish express two type II interferons, IFNγ and fish-specific IFNγ (IFNγ-related or IFNγrel). We previously reported the presence of two IFNγrel genes, IFNγrel 1 and IFNγrel 2, which exhibit potent antiviral activity in the Ginbuna crucian carp, Carassius auratus langsdorfii. We also found that IFNγrel 1 increased allograft rejection; however, the IFNγrel 1 receptor(s) and signaling pathways underlying this process have not yet been elucidated. In this study, we examined the unique signaling mechanism of IFNγrel 1 and its receptors. The phosphorylation and transcriptional activation of STAT6 in response to recombinant Ginbuna IFNγrel 1 (rgIFNγrel 1) was observed in Ginbuna-derived cells. Binding of rgIFNγrel 1 to Class II cytokine receptor family members (Crfbs), Crfb5 and Crfb17, which are also known as IFNAR1 and IFNGR1-1, respectively, was detected by flow cytometry. Expression of the IFNγrel 1-inducible antiviral gene, Isg15, was highest in Crfb5- and Crfb17-overexpressing GTS9 cells. Dimerization of Crfb5 and Crfb17 was detected by chemical crosslinking. The results indicate that IFNγrel 1 activates Stat6 through an interaction with unique pairs of receptors, Crfb5 and Crfb17. Indeed, this cascade is distinct from not only that of IFNγ but also that of known IFNs in other vertebrates. IFNs may be classified by their receptor and signal transduction pathways. Taken together, IFNγrel 1 may be classified as a novel type of IFN family member in vertebrates. Our findings provide important information on interferon gene evolution in bony fish.
MeSH term(s)	Animals ; Interferon-gamma/metabolism ; Interferons ; Carps/metabolism ; Signal Transduction ; Antiviral Agents ; Mammals
Chemical Substances	Interferon-gamma (82115-62-6) ; Interferons (9008-11-1) ; Antiviral Agents
Language	English
Publishing date	2024-02-06
Publishing country	England
Document type	Journal Article
ZDB-ID	2651702-4
ISSN	2211-5463 ; 2211-5463
ISSN (online)	2211-5463
ISSN	2211-5463
DOI	10.1002/2211-5463.13769
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Authors' reply to the letter to the editor on "Managing geriatric syndromes: necessity of pharmacists' involvements" by Kojima.

Mizokami, Fumihiro / Hasegawa, Sho / Mizuno, Tomohiro / Yabu, Takeshi / Kameya, Yoshitaka / Hayakawa, Yuji / Arai, Hidenori

Geriatrics & gerontology international

2024 Volume 24, Issue 4, Page(s) 448–450

MeSH term(s)	Humans ; Aged ; Pharmacists ; Syndrome
Language	English
Publishing date	2024-03-11
Publishing country	Japan
Document type	Letter
ZDB-ID	2113849-7
ISSN	1447-0594 ; 1444-1586
ISSN (online)	1447-0594
ISSN	1444-1586
DOI	10.1111/ggi.14859
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Article ; Online: Investigation of geriatric syndromes associated with medication in Japan using insurance claims data.

Hasegawa, Sho / Mizokami, Fumihiro / Mizuno, Tomohiro / Yabu, Takeshi / Kameya, Yoshitaka / Hayakawa, Yuji / Arai, Hidenori

Geriatrics & gerontology international

2023 Volume 24, Issue 1, Page(s) 61–67

Abstract: Aim: Multiple risk factors are involved in geriatric syndrome (GS) occurring in older adults. Although drug therapy often contributes to GS, the specific causes among older adults in Japan remain unclear. In this study, we examined the possible ... ...

Abstract	Aim: Multiple risk factors are involved in geriatric syndrome (GS) occurring in older adults. Although drug therapy often contributes to GS, the specific causes among older adults in Japan remain unclear. In this study, we examined the possible prescribing cascade rate among older outpatients eligible for Late-stage Elderly Health Insurance and elucidated the differences between GS and GS associated with medication (GSAM) trends. Methods: This retrospective study enrolled patients from health insurance claims data in Japan between October 2018 and March 2019; hospitalized patients were excluded. Two groups were identified among the participants with GS: GS (no use of GS-causing medications) and possible-GSAM (p-GSAM; use of GS-causing medications). The collected data were analyzed using the Bell Curve for Excel, and statistical significance was set at P < 0.05. Results: In total, 137 781 outpatients were enrolled. Of the 32 259 outpatients who did not use GS-causing medications, 7342 were classified into the GS group. Among 105 522 outpatients who used GS-causing medications, 8347 were classified as having p-GSAM. The mean number of prescriptions was significantly higher in the p-GSAM group than in the GS group (P < 0.01). Furthermore, all GS symptoms showed significant differences, with impaired appetite being the most prevalent in the p-GSAM group than in the GS group (P < 0.01). A possible prescribing cascade was suspected in 2826 (33.9%) of 8347 outpatients in the p-GSAM group. Conclusion: Impaired appetite in patients taking GS-causing medications might lead to prescribing cascades. Further studies are needed to prevent such prescribing cascades. Geriatr Gerontol Int 2024; 24: 61-67.
MeSH term(s)	Humans ; Aged ; Retrospective Studies ; Japan/epidemiology ; Risk Factors ; Outpatients ; Insurance
Language	English
Publishing date	2023-12-12
Publishing country	Japan
Document type	Journal Article
ZDB-ID	2113849-7
ISSN	1447-0594 ; 1444-1586
ISSN (online)	1447-0594
ISSN	1444-1586
DOI	10.1111/ggi.14755
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Article: Alteration of hemoglobin ß gene expression in mucosal tissues of Japanese flounder, Paralichthys olivaceus, in response to heat stress, Edwardsiella piscicida infection, and immunostimulants administration

Mori, Misato / Shibasaki, Yasuhiro / Namba, Aki / Yabu, Takeshi / Wada, Noriko / Shiba, Hajime / Anzai, Hirosi / Mano, Nobuhiro

Fish and shellfish immunology reports. 2022 Dec., v. 3

2022

Abstract: Hemoglobin beta (Hbß) is a heme-binding protein capable of oxygen delivery. The oligopeptides derived from Hbβ in fish mucus are active against a variety of gram-negative bacteria and protozoa. To gain information on the physiological and immunological ... ...

Abstract	Hemoglobin beta (Hbß) is a heme-binding protein capable of oxygen delivery. The oligopeptides derived from Hbβ in fish mucus are active against a variety of gram-negative bacteria and protozoa. To gain information on the physiological and immunological roles of Hbβ in the mucosal tissues of fish, we analyzed changes in Hbß gene expression levels in the epidermis, gills, and intestine of Japanese flounder, Paralichthys olivaceus, in response to heat stress, Edwardsiella piscicida infection, and trial feeding of immunostimulants, high-concentration ascorbic acid (AsA) or lactoferrin (LF). The results of quantitative real-time PCR showed that expression of the Hbß gene in the gills decreased markedly when exposed to heat stress, whereas that in the epidermis exhibited an increase 3h after infection with E. piscicida. Seven days after starting to feed either immunostimulant, epidermal Hbß gene expression in all AsA or LF dose groups was significantly higher than in the control group. The results of in situ hybridization showed that the abundance and intensity of the stained cells in the epidermis and in the gills were consistent with the expression levels of Hbß gene obtained from the infection and immunosuppressant experiments and the heat stress experiment, respectively. Our results suggest that mucosal Hbβ gene expression is closely related to physiological and immunological status and could be a useful indicator for monitoring condition of fish health.
Keywords	Edwardsiella piscicida ; Paralichthys olivaceus ; Protozoa ; ascorbic acid ; fish health ; gene expression ; genes ; heat stress ; hemoglobin ; hybridization ; immunostimulants ; immunosuppressive agents ; intestines ; lactoferrin ; mucus ; oligopeptides ; oxygen ; quantitative polymerase chain reaction ; shellfish
Language	English
Dates of publication	2022-12
Publishing place	Elsevier Ltd
Document type	Article
ISSN	2667-0119
DOI	10.1016/j.fsirep.2021.100049
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Alteration of hemoglobin ß gene expression in mucosal tissues of Japanese flounder,

Mori, Misato / Shibasaki, Yasuhiro / Namba, Aki / Yabu, Takeshi / Wada, Noriko / Shiba, Hajime / Anzai, Hirosi / Mano, Nobuhiro

Fish and shellfish Immunology reports

2022 Volume 3, Page(s) 100049

Abstract	Hemoglobin beta (Hbß) is a heme-binding protein capable of oxygen delivery. The oligopeptides derived from Hbβ in fish mucus are active against a variety of gram-negative bacteria and protozoa. To gain information on the physiological and immunological roles of Hbβ in the mucosal tissues of fish, we analyzed changes in Hbß gene expression levels in the epidermis, gills, and intestine of Japanese flounder,
Language	English
Publishing date	2022-01-08
Publishing country	England
Document type	Journal Article
ISSN	2667-0119
ISSN (online)	2667-0119
DOI	10.1016/j.fsirep.2021.100049
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Article: Enhancement of immune proteins expression in skin mucus of Japanese flounder Paralicthys olivaceus upon feeding a diet supplemented with high concentration of ascorbic acid

Mori, Misato / Ito, Tasuku / Washio, Ryota / Shibasaki, Yasuhiro / Namba, Aki / Yabu, Takeshi / Iwazaki, Dai / Wada, Noriko / Anzai, Hirosi / Shiba, Hajime / Nakanishi, Teruyuki / Mano, Nobuhiro

Fish & shellfish immunology. 2021 July, v. 114

2021

Abstract: To search immune defense proteins in skin mucus of Japanese flounder fed with a diet containing high concentration of ascorbic acid, we carried out 2D-PAGE and compared the resolved pattern of proteins between control group that fed commercial diet and ... ...

Abstract	To search immune defense proteins in skin mucus of Japanese flounder fed with a diet containing high concentration of ascorbic acid, we carried out 2D-PAGE and compared the resolved pattern of proteins between control group that fed commercial diet and ascorbic acid supplemented group (AsA group) fed a diet supplemented with high concentration of ascorbic acid (2,000 mg/kg) for 7 days. The results revealed that there were many proteins exhibited distinct increase in AsA group. Among them, 6 regions that showed a dramatic elevation were chosen for protein identification using LC-MS/MS analysis and Mascot database search. Six proteins were identified, i.e. serotransferrin (Sero), transferrin (Trans), warm temperature acclimation-related 65 kDa protein (Wap65), complement component c3 (C3), hemoglobin beta-A chain (Hbß) and apolipoprotein A-1 (Apo). Quantitative RT-PCR analysis showed that the mRNA level of Hbß in epidermis of AsA group gave much higher increase (11.6 folds) than control group; the levels of Sero/Trans, Wap65, C3 and Apo showed no apparent difference between the two groups. The mRNA levels of wap65 and c3 in the liver and Apo in the kidney of AsA group exhibited significant increase in comparison to control group. In the case of secreted immunoglobulin M (IgM) and lysozyme (lyz), no difference of the mRNA levels of IgM in epidermis, gill, kidney, spleen and intestine, and lyz in epidermis, gill, spleen and intestine, was observed. The results of in situ hybridization confirmed the elevation of Hbß mRNA level in the epidermis tissue of AsA group. Our present study provided additional evidence showing the effectiveness of AsA in activating innate immune defense system in skin mucosal tissue of fish.
Keywords	Paralichthys olivaceus ; apolipoprotein A-I ; ascorbic acid ; complement ; databases ; diet ; gene expression ; hemoglobin ; hybridization ; immune response ; innate immunity ; intestines ; kidneys ; liver ; lysozyme ; mucus ; reverse transcriptase polymerase chain reaction ; shellfish ; spleen ; temperature ; transferrin
Language	English
Dates of publication	2021-07
Size	p. 20-27.
Publishing place	Elsevier Ltd
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	1067738-0
ISSN	1095-9947 ; 1050-4648
ISSN (online)	1095-9947
ISSN	1050-4648
DOI	10.1016/j.fsi.2021.04.009
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Article: Peculiar Expression of CD3-Epsilon in Kidney of Ginbuna Crucian Carp.

Miyazawa, Ryuichiro / Murata, Norifumi / Matsuura, Yuta / Shibasaki, Yasuhiro / Yabu, Takeshi / Nakanishi, Teruyuki

Frontiers in immunology

2018 Volume 9, Page(s) 1321

Abstract: TCR/CD3 complex is composed of the disulfide-linked TCR-αβ heterodimer that recognizes the antigen as a peptide presented by the MHC, and non-covalently paired CD3γε- and δε-chains together with disulfide-linked ζ-chain homodimers. The CD3 chains play ... ...

Abstract	TCR/CD3 complex is composed of the disulfide-linked TCR-αβ heterodimer that recognizes the antigen as a peptide presented by the MHC, and non-covalently paired CD3γε- and δε-chains together with disulfide-linked ζ-chain homodimers. The CD3 chains play key roles in T cell development and T cell activation. In the present study, we found nor or extremely lower expression of CD3ε in head- and trunk-kidney lymphocytes by flow cytometric analysis, while CD3ε was expressed at the normal level in lymphocytes from thymus, spleen, intestine, gill, and peripheral blood. Furthermore, CD4-1
Language	English
Publishing date	2018
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606827-8
ISSN	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2018.01321
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Article ; Online: Purification and characterization of a fish granzymeA involved in cell-mediated immunity.

Matsuura, Yuta / Yabu, Takeshi / Shiba, Hajime / Moritomo, Tadaaki / Nakanishi, Teruyuki

Developmental and comparative immunology

2016 Volume 60, Page(s) 33–40

Abstract: Granzymes are serine proteases involved in the induction of cell death against non-self cells. The enzymes differ in their primary substrate specificity and have one of four hydrolysis activities: tryptase, Asp-ase, Met-ase and chymase. Although granzyme ...

Abstract	Granzymes are serine proteases involved in the induction of cell death against non-self cells. The enzymes differ in their primary substrate specificity and have one of four hydrolysis activities: tryptase, Asp-ase, Met-ase and chymase. Although granzyme genes have been isolated from several fishes, evidence for their involvement in cytotoxicity has not yet been reported. In the present study, we attempted to purify and characterize a fish granzyme involved in cytotoxicity using ginbuna crucian carp. The cytotoxicity of leukocytes was significantly inhibited by the serine protease inhibitor ''3, 4-dichloroisocoumarin''. In addition, we found that granzymeA-like activity (hydrolysis of Z-GPR-MCA) was inhibited by the same inhibitor and significantly enhanced by allo-antigen stimulation in vivo. Proteins from leukocyte extracts were subjected to two steps of chromatographic purification using benzamidine-Sepharose and SP-Sepharose. The molecular weight of the purified enzyme was estimated to be 26,900 Da by SDS-PAGE analysis. The purified enzyme displayed a Km of 220 μM, a Kcat of 21.7 sec(-1) and a Kcat/Km of 98,796 sec(-1) M(-1) with an optimal pH of 9.5 for the Z-GPR-MCA substrate. The protease was totally inhibited by serine protease inhibitors and showed granzymeA-like substrate specificity. Therefore, we conclude that the purified enzyme belongs to the mammalian granzymeA (EC 3.4.21.78) and appears to be involved in cytotoxicity in fish.
MeSH term(s)	Animals ; Carps/immunology ; Cell Line ; Fish Proteins/antagonists & inhibitors ; Fish Proteins/chemistry ; Fish Proteins/isolation & purification ; Granzymes/antagonists & inhibitors ; Granzymes/chemistry ; Granzymes/isolation & purification ; Hydrogen-Ion Concentration ; Hydrolysis ; Immunity, Cellular ; Kinetics ; Protease Inhibitors/chemistry ; Proteolysis ; Substrate Specificity
Chemical Substances	Fish Proteins ; Protease Inhibitors ; Granzymes (EC 3.4.21.-)
Language	English
Publishing date	2016-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	752411-0
ISSN	1879-0089 ; 0145-305X
ISSN (online)	1879-0089
ISSN	0145-305X
DOI	10.1016/j.dci.2016.02.011
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Zs.A 1327: Show issues

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Article ; Online: Enhancement of immune proteins expression in skin mucus of Japanese flounder Paralicthys olivaceus upon feeding a diet supplemented with high concentration of ascorbic acid.

Mori, Misato / Ito, Tasuku / Washio, Ryota / Shibasaki, Yasuhiro / Namba, Aki / Yabu, Takeshi / Iwazaki, Dai / Wada, Noriko / Anzai, Hirosi / Shiba, Hajime / Nakanishi, Teruyuki / Mano, Nobuhiro

Fish & shellfish immunology

2021 Volume 114, Page(s) 20–27

Abstract	To search immune defense proteins in skin mucus of Japanese flounder fed with a diet containing high concentration of ascorbic acid, we carried out 2D-PAGE and compared the resolved pattern of proteins between control group that fed commercial diet and ascorbic acid supplemented group (AsA group) fed a diet supplemented with high concentration of ascorbic acid (2,000 mg/kg) for 7 days. The results revealed that there were many proteins exhibited distinct increase in AsA group. Among them, 6 regions that showed a dramatic elevation were chosen for protein identification using LC-MS/MS analysis and Mascot database search. Six proteins were identified, i.e. serotransferrin (Sero), transferrin (Trans), warm temperature acclimation-related 65 kDa protein (Wap65), complement component c3 (C3), hemoglobin beta-A chain (Hbß) and apolipoprotein A-1 (Apo). Quantitative RT-PCR analysis showed that the mRNA level of Hbß in epidermis of AsA group gave much higher increase (11.6 folds) than control group; the levels of Sero/Trans, Wap65, C3 and Apo showed no apparent difference between the two groups. The mRNA levels of wap65 and c3 in the liver and Apo in the kidney of AsA group exhibited significant increase in comparison to control group. In the case of secreted immunoglobulin M (IgM) and lysozyme (lyz), no difference of the mRNA levels of IgM in epidermis, gill, kidney, spleen and intestine, and lyz in epidermis, gill, spleen and intestine, was observed. The results of in situ hybridization confirmed the elevation of Hbß mRNA level in the epidermis tissue of AsA group. Our present study provided additional evidence showing the effectiveness of AsA in activating innate immune defense system in skin mucosal tissue of fish.
Language	English
Publishing date	2021-04-20
Publishing country	England
Document type	Journal Article
ZDB-ID	1067738-0
ISSN	1095-9947 ; 1050-4648
ISSN (online)	1095-9947
ISSN	1050-4648
DOI	10.1016/j.fsi.2021.04.009
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Molecular cloning of two gonadotropin receptors in mummichog Fundulus heteroclitus and their gene expression during follicular development and maturation.

Ohkubo, Makoto / Yabu, Takeshi / Yamashita, Michiaki / Shimizu, Akio

General and comparative endocrinology

2013 Volume 184, Page(s) 75–86

Abstract: Two cDNAs encoding gonadotropin receptors, follicle-stimulating hormone receptor (FSHR) and luteinizing hormone receptor (LHR) were cloned from mummichog (Fundulus heteroclitus) ovary. Deduced amino acid sequences of the mummichog FSHR (fhFSHR) and LHR ( ... ...

Abstract	Two cDNAs encoding gonadotropin receptors, follicle-stimulating hormone receptor (FSHR) and luteinizing hormone receptor (LHR) were cloned from mummichog (Fundulus heteroclitus) ovary. Deduced amino acid sequences of the mummichog FSHR (fhFSHR) and LHR (fhLHR) showed high homologies to teleost FSHRs (77-53%) and teleost LHRs (76-62%), respectively. Both the fhFSHR and fhLHR are composed of a typical structural architecture of glycoprotein hormone receptors consisting of the large N-terminal extracellular domain, the transmembrane domain containing seven cell surface membrane-spanning regions, and the intracellular domain. Functional analysis using HEK293 cells stably expressing the fhFSHR or fhLHR demonstrated that both the receptors are specifically activated by mummichog FSH or LH, respectively. Reverse transcription-polymerase chain reaction revealed that both the fhFSHR and fhLHR were expressed in the ovary, testis, and pituitary, and the fhLHR was also expressed in several extra-gonadal tissues. Real-time quantitative-PCR analysis revealed that the fhFSHR gene was abundantly expressed in developing follicles whereas expression of the fhLHR gene markedly increased in follicles of the final maturational stage. These results indicate that gonadotropin stimulation on follicles is regulated by the two distinct pathways via their cognate receptors.
MeSH term(s)	Animals ; Female ; Follicle Stimulating Hormone/metabolism ; Fundulidae/genetics ; Fundulidae/metabolism ; Luteinizing Hormone/metabolism ; Ovarian Follicle/metabolism ; Receptors, FSH/genetics ; Receptors, FSH/metabolism ; Receptors, Gonadotropin/genetics ; Receptors, Gonadotropin/metabolism ; Receptors, LH/genetics ; Receptors, LH/metabolism ; Reverse Transcriptase Polymerase Chain Reaction
Chemical Substances	Receptors, FSH ; Receptors, Gonadotropin ; Receptors, LH ; Luteinizing Hormone (9002-67-9) ; Follicle Stimulating Hormone (9002-68-0)
Language	English
Publishing date	2013-04-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	1851-x
ISSN	1095-6840 ; 0016-6480
ISSN (online)	1095-6840
ISSN	0016-6480
DOI	10.1016/j.ygcen.2012.12.019
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