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Article: Editorial: Brain abnormalities due to genetic alterations or developmental exposure to environmental factors.

Sawada, Kazuhiko / Yoshiki, Atsushi / Saito, Shigeyoshi

2022 Volume 16, Page(s) 944861

Language	English
Publishing date	2022-07-26
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2411902-7
ISSN	1662-453X ; 1662-4548
ISSN (online)	1662-453X
ISSN	1662-4548
DOI	10.3389/fnins.2022.944861
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Article ; Online: Histological studies on male sterility of hybrids between laboratory and wild mouse strains: (hybrid sterility/Hst-1 locus/spermatogenesis/chimera/Sertoli cell).

Yoshiki, Atsushi / Moriwaki, Kazuo / Sakakura, Teruyo / Kusakabe, Moriaki

Development, growth & differentiation

2023 Volume 35, Issue 3, Page(s) 271–281

Abstract: In this study the cellular mechanisms of male sterility in F1 hybrids (BNF1) between BALB/c and wild-derived M.MUS-NJL (NJL) was investigated. Cell proliferation and differentiation in the sterile testis were examined by bromodeoxyuridine-labeling and ... ...

Abstract	In this study the cellular mechanisms of male sterility in F1 hybrids (BNF1) between BALB/c and wild-derived M.MUS-NJL (NJL) was investigated. Cell proliferation and differentiation in the sterile testis were examined by bromodeoxyuridine-labeling and use of germ cell stage-specific antibodies. In BNF1 testes, spermatogonia actively proliferated with a seminiferous epithelial cycle, and were retained in the basal layer of the tubules. However, preleptotene, leptotene and zygotene spermatocytes moved to the adluminal region. Immunohistological data with germ cell stage-specific antibodies indicated the presence of few, if any, pachytene spermatocytes in BNF1 testes. Thus, spermatogenesis seemed to be blocked at the zygotene stage. For examination of germ cell-Sertoli cell interactions, testes of aggregation chimeras between BNF1 and C3H/HeN were analyzed immunohistologically with C3H-specific antibody. Results showed that spermatogenesis of C3H-germ cells was normal, even when these cells in contact with BNF1-Sertoli cells. Differentiation of BNF1-germ cells progressed from zygotene to pachytene stage spermatocytes when these cells were surrounded by C3H-Sertoli cells, but never proceeded beyond the pachytene stage. These observations suggest that at least two different cellular factors may be involved in spermatogenesis, one acting in the germ cells and the other mediated by Sertoli cells. Furthermore, mating experiments revealed that the degree of spermatogenesis varied in different F1 hybrids, and that the major sterility factor was closely linked to the T-locus on chromosome 17.
Language	English
Publishing date	2023-06-06
Publishing country	Japan
Document type	Journal Article
ZDB-ID	280433-5
ISSN	1440-169X ; 0012-1592
ISSN (online)	1440-169X
ISSN	0012-1592
DOI	10.1111/j.1440-169X.1993.00271.x
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Article ; Online: Substrains matter in phenotyping of C57BL/6 mice.

Mekada, Kazuyuki / Yoshiki, Atsushi

Experimental animals

2021 Volume 70, Issue 2, Page(s) 145–160

Abstract: The inbred mouse strain C57BL/6 has been widely used as a background strain for spontaneous and induced mutations. Developed in the 1930s, the C57BL/6 strain diverged into two major groups in the 1950s, namely, C57BL/6J and C57BL/6N, and more than 20 ... ...

Abstract	The inbred mouse strain C57BL/6 has been widely used as a background strain for spontaneous and induced mutations. Developed in the 1930s, the C57BL/6 strain diverged into two major groups in the 1950s, namely, C57BL/6J and C57BL/6N, and more than 20 substrains have been established from them worldwide. We previously reported genetic differences among C57BL/6 substrains in 2009 and 2015. Since then, dozens of reports have been published on phenotypic differences in behavioral, neurological, cardiovascular, and metabolic traits. Substrains need to be chosen according to the purpose of the study because phenotypic differences might affect the experimental results. In this paper, we review recent reports of phenotypic and genetic differences among C57BL/6 substrains, focus our attention on the proper use of C57BL/6 and other inbred strains in the era of genome editing, and provide the life science research community wider knowledge about this subject.
MeSH term(s)	Animals ; Mice ; Mice, Inbred Strains/genetics ; Mice, Inbred Strains/physiology ; Phenotype ; Species Specificity
Language	English
Publishing date	2021-01-14
Publishing country	Japan
Document type	Journal Article ; Review
ZDB-ID	2088228-2
ISSN	1881-7122 ; 1341-1357 ; 0007-5124
ISSN (online)	1881-7122
ISSN	1341-1357 ; 0007-5124
DOI	10.1538/expanim.20-0158
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Article ; Online: Genetic quality: a complex issue for experimental study reproducibility.

Yoshiki, Atsushi / Ballard, Gregory / Perez, Ana V

Transgenic research

2022 Volume 31, Issue 4-5, Page(s) 413–430

Abstract: Laboratory animal research involving mice, requires consideration of many factors to be controlled. Genetic quality is one factor that is often overlooked but is essential for the generation of reproducible experimental results. Whether experimental ... ...

Abstract	Laboratory animal research involving mice, requires consideration of many factors to be controlled. Genetic quality is one factor that is often overlooked but is essential for the generation of reproducible experimental results. Whether experimental research involves inbred mice, spontaneous mutant, or genetically modified strains, exercising genetic quality through careful breeding, good recordkeeping, and prudent quality control steps such as validation of the presence of mutations and verification of the genetic background, will help ensure that experimental results are accurate and that reference controls are representative for the particular experiment. In this review paper, we will discuss various techniques used for the generation of genetically altered mice, and the different aspects to be considered regarding genetic quality, including inbred strains and substrains used, quality check controls during and after genetic manipulation and breeding. We also provide examples for when to use the different techniques and considerations on genetic quality checks. Further, we emphasize on the importance of establishing an in-house genetic quality program.
MeSH term(s)	Animals ; Mice ; Mice, Inbred Strains ; Mutation ; Reproducibility of Results
Language	English
Publishing date	2022-06-25
Publishing country	Netherlands
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	31620-9
ISSN	1573-9368 ; 0962-8819
ISSN (online)	1573-9368
ISSN	0962-8819
DOI	10.1007/s11248-022-00314-w
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Article ; Online: APOE-ε4 allele[s]-associated adverse events reported from placebo arm in clinical trials for Alzheimer's disease

Kenichiro Sato / Yoshiki Niimi / Ryoko Ihara / Kazushi Suzuki / Atsushi Iwata / Takeshi Iwatsubo

Frontiers in Dementia, Vol

implications for anti-amyloid beta therapy

2024 Volume 2

Abstract: APOE-ε4 allele[s] is a risk factor for Alzheimer's disease (AD) and Amyloid-Related Imaging Abnormalities (ARIA) in anti-amyloid beta therapy, and is also associated with cerebrovascular risk factors such as hyperlipidemia or atherosclerosis. During AD ... ...

Abstract	APOE-ε4 allele[s] is a risk factor for Alzheimer's disease (AD) and Amyloid-Related Imaging Abnormalities (ARIA) in anti-amyloid beta therapy, and is also associated with cerebrovascular risk factors such as hyperlipidemia or atherosclerosis. During AD clinical trials, APOE-ε4 carriers may experience neuropsychiatric adverse events (AEs) related to these risks, complicating the differentiation of ARIA from cerebrovascular events based on symptoms. This study aimed to examine the hypothetical impact of considering the APOE-ε4 allele's risk for non-ARIA AEs during AD clinical trials. We used data from the Critical Path for Alzheimer's Disease (CPAD) from the placebo arm of randomized controlled trials (RCT) for AD treatment. We determined whether AEs were reported more frequently in APOE-ε4 carriers, quantifying with reporting odds ratio (ROR) using a mixed effect model. We also evaluated the association between ROR levels and the prior probability that an AE is symptomatic ARIA. We analyzed 6,313 patients with AD or mild cognitive impairment in 28 trials. Of the prespecified 35 neuropsychiatric or related AEs, several had a significantly high ROR: “delusion” (ROR = 4.133), “confusional state” (ROR = 1.419), “muscle spasms” (ROR = 9.849), “irritability” (ROR = 12.62), “sleep disorder” (ROR = 2.944), or “convulsion” (ROR = 13.00). However, none remained significant after adjusting for Mini-Mental State Examination scores. There is no strong evidence to suggest that specific neuropsychiatric AEs occur more frequently without drug treatment association among APOE-ε4 carriers. The influence of APOE-ε4 allele[s] on the clinicians' assessment of the likelihood of ARIA during safety monitoring in anti-amyloid beta monoclonal antibody treatment might be unchanged, thus maintaining the current level of awareness of clinicians of AEs.
Keywords	adverse event ; APOE ; Amyloid-Related Imaging Abnormalities ; ARIA ; Alzheimer's disease ; disease-modifying therapy ; Medicine ; R
Subject code	610 ; 616
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
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Article: Genetic quality: a complex issue for experimental study reproducibility

Yoshiki, Atsushi / Ballard, Gregory / Perez, Ana V.

Transgenic research. 2022 Oct., v. 31, no. 4-5

2022

Abstract	Laboratory animal research involving mice, requires consideration of many factors to be controlled. Genetic quality is one factor that is often overlooked but is essential for the generation of reproducible experimental results. Whether experimental research involves inbred mice, spontaneous mutant, or genetically modified strains, exercising genetic quality through careful breeding, good recordkeeping, and prudent quality control steps such as validation of the presence of mutations and verification of the genetic background, will help ensure that experimental results are accurate and that reference controls are representative for the particular experiment. In this review paper, we will discuss various techniques used for the generation of genetically altered mice, and the different aspects to be considered regarding genetic quality, including inbred strains and substrains used, quality check controls during and after genetic manipulation and breeding. We also provide examples for when to use the different techniques and considerations on genetic quality checks. Further, we emphasize on the importance of establishing an in-house genetic quality program.
Keywords	animal research ; genetic background ; genetic engineering ; laboratory animals ; mutants ; quality control
Language	English
Dates of publication	2022-10
Size	p. 413-430.
Publishing place	Springer International Publishing
Document type	Article
Note	Review
ZDB-ID	31620-9
ISSN	1573-9368 ; 0962-8819
ISSN (online)	1573-9368
ISSN	0962-8819
DOI	10.1007/s11248-022-00314-w
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Comparison of imaging changes in pulmonary artery diameter at the occlusion site using silk or metal clamps for pulmonary artery troubles.

Chiba, Yoshiki / Miyajima, Masahiro / Takahashi, Yuki / Shindo, Yuma / Tsuruta, Kodai / Maki, Ryunosuke / Watanabe, Atsushi

European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery

2024 Volume 65, Issue 3

Abstract: Objectives: We analysed our clinical experience using silk sutures [the double-loop technique (DLT)] or DeBakey type vascular clamp (DeBakey clamp) for pulmonary artery (PA) troubles during anatomical lung resection to validate its practicality and ... ...

Abstract	Objectives: We analysed our clinical experience using silk sutures [the double-loop technique (DLT)] or DeBakey type vascular clamp (DeBakey clamp) for pulmonary artery (PA) troubles during anatomical lung resection to validate its practicality and safety. Methods: We retrospectively reviewed the records of patients who underwent either of the above clamping techniques during anatomical lung resection at our hospital between April 2007 and August 2022. We measured the PA diameter at the occlusion site on computed tomography images acquired within 1 year pre- and postoperatively. The difference between pre- and postoperative diameters of the occlusion sites was calculated as the change in the PA diameter. We zoned the occlusion site of the PA to adjust for variation. PA deformation was evaluated as an adverse event caused by clamping. Results: Ultimately, 27 and 26 patients who underwent the DLT and DeBakey clamp, respectively, were included. No additional injury due to the clamp procedure was found in either group. For zone R1/L1, defined as the main PA, the median changes in the PA diameter were 0.02 (-0.7 to 0.27) mm for the DLT and 0.36 (-0.28 to 0.89) mm for the DeBakey clamp. No significant differences were observed between the 2 groups (P = 0.106). Furthermore, no aneurysms, dissections, or stenoses were found in either group. Conclusions: The DLT and DeBakey clamp had only minimal effects on the occlusion site of the PA. The DLT is a practical thoracoscopic technique for PA bleeding when primary haemostasis has been achieved.
MeSH term(s)	Humans ; Pulmonary Artery/diagnostic imaging ; Pulmonary Artery/surgery ; Silk ; Retrospective Studies ; Tomography, X-Ray Computed ; Thoracic Surgery, Video-Assisted/methods
Chemical Substances	Silk
Language	English
Publishing date	2024-02-07
Publishing country	Germany
Document type	Journal Article
ZDB-ID	639293-3
ISSN	1873-734X ; 1010-7940 ; 1567-4258
ISSN (online)	1873-734X
ISSN	1010-7940 ; 1567-4258
DOI	10.1093/ejcts/ezae034
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Article: Advertisement by medical facilities as an opportunity route of APOE genetic testing in Japan: a website analysis.

Sato, Kenichiro / Niimi, Yoshiki / Ihara, Ryoko / Iwata, Atsushi / Ikeuchi, Takeshi / Iwatsubo, Takeshi

Journal of community genetics

2024 Volume 15, Issue 2, Page(s) 195–204

Abstract: The APOE-ε4 allele(s) is a strong risk factor for Alzheimer's disease (AD). A significant point of access for this allele testing is through services provided by medical facilities in Japan, which advertise out-of-insurance APOE testing on their websites. ...

Abstract	The APOE-ε4 allele(s) is a strong risk factor for Alzheimer's disease (AD). A significant point of access for this allele testing is through services provided by medical facilities in Japan, which advertise out-of-insurance APOE testing on their websites. There is a concern that website advertisements for APOE testing may influence the ability for individuals to adequately self-determine whether to undergo APOE testing. We conducted a cross-sectional survey on medical facility websites in Japan advertising APOE genetic testing. We predefined desirable features for advertisement descriptions based on legal regulations and guidelines published by relevant professional societies and evaluated each website according to these features. We identified 220 medical facilities that had posted advertisements on their websites for the provision of APOE genetic testing, of which 85% were small clinics. Contact information, details, and costs of testing were described in most of the websites. Meanwhile, features such as "explaining APOE as a risk gene," "notes on interpreting APOE results," or "explaining examination methods" (e.g., blood sampling) were described to a variable degree depending on individual facilities. "Notes on genetic testing" or "referring to genetic counseling" were hardly referred to, and specialists with appropriate expertise were considered to participate in clinical practice in approximately one-third of these facilities providing APOE testing services. These website evaluation results showed moderate to substantial reliability between independent raters. These results suggest that self-determination of pursuing out-of-insurance APOE testing at some medical facilities in Japan may possibly be influenced in an inappropriate manner, at least in its entry route of taking the test.
Language	English
Publishing date	2024-01-16
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2543127-4
ISSN	1868-6001 ; 1868-310X
ISSN (online)	1868-6001
ISSN	1868-310X
DOI	10.1007/s12687-024-00697-9
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Article ; Online: Greb1 Transiently Accelerates Pancreatic β-Cell Proliferation in Diabetic Mice Exposed to Estradiol.

Inada, Akari / Yasunami, Yohichi / Yoshiki, Atsushi / Nabeshima, Yo-Ichi / Inada, Oogi

The American journal of pathology

2023 Volume 193, Issue 8, Page(s) 1081–1100

Abstract: Decrease of pancreatic β cells leads to diabetes. In an inducible cAMP early suppressor (ICER-Iγ) transgenic mouse model of severe type 2 diabetes with reduced insulin production and depleted β cells, supplementation with high concentrations of 17β- ... ...

Abstract	Decrease of pancreatic β cells leads to diabetes. In an inducible cAMP early suppressor (ICER-Iγ) transgenic mouse model of severe type 2 diabetes with reduced insulin production and depleted β cells, supplementation with high concentrations of 17β-estradiol (E2) markedly enhances β-cell proliferation and normalizes glucose levels. The current study explored the underlying mechanisms leading to a dynamic increase of β cells and pathologic changes in diabetic mice exposed to E2. Gene expression profiling of pancreatic islets of 6-month-old ICER-transgenic mice recovering from diabetes due to elevated E2 levels identified growth regulation by estrogen in breast cancer 1 (Greb1) as a gene significantly up-regulated during the recovery phase. To substantiate this, β-cell-specific Greb1-deficient mice were generated, and Greb1 was shown to be essential for recovery of depleted β cells in diabetic mice. Graft growth and glucose lowering were observed in 50 islets with increased Greb1 expression transplanted adjacent to E2 pellets beneath the kidney capsule of streptozotocin-induced diabetic mice. Greb1 expression due to a drastic increase in exogenous or endogenous E2 was transient and closely correlated with changes in E2-related and some cell cycle-related genes. These findings provide new insights into in vivo proliferation of deficient β cells and suggest the possibility of new therapeutic approaches targeting pancreatic β cells that could revolutionize the concept of diabetes treatment, which has been considered difficult to cure completely.
MeSH term(s)	Mice ; Animals ; Estradiol/pharmacology ; Diabetes Mellitus, Experimental ; Diabetes Mellitus, Type 2 ; Cell Proliferation ; Mice, Transgenic ; Glucose
Chemical Substances	Estradiol (4TI98Z838E) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2023-04-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2943-9
ISSN	1525-2191 ; 0002-9440
ISSN (online)	1525-2191
ISSN	0002-9440
DOI	10.1016/j.ajpath.2023.04.012
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Article ; Online: [Survey on the Current Advertising and Sales of Mucuna pruriens in Consumer-to-consumer Internet Trading in Japan].

Sato, Kenichiro / Hida, Ayumi / Niimi, Yoshiki / Iwata, Atsushi / Iwatsubo, Takeshi

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan

2023 Volume 143, Issue 12, Page(s) 1057–1067

Abstract: Mucuna pruriens (MP) is leguminous plant which contains 5% of L-3,4-dihydroxyphenylalanine (levodopa) in its seeds. It may have a potential to be used as an alternative therapy for Parkinson's disease (PD). Meanwhile, there is a concern in terms of ... ...

Abstract	Mucuna pruriens (MP) is leguminous plant which contains 5% of L-3,4-dihydroxyphenylalanine (levodopa) in its seeds. It may have a potential to be used as an alternative therapy for Parkinson's disease (PD). Meanwhile, there is a concern in terms of public health that MP products can be overused by patients with PD. As an entry for patients with PD to acquire MP products in Japan, they are often purchased via internet auctions or free markets. MP products are not reagrded as 'pharmatheutical' by Japanese law as long as the specific legal requirements on advertisements are met, so that the MP products can be advertised or sold without any permission from the authorities. In this study, we aimed to conduct internet survey as to the complianse status of these legal requirements. Several major internet auction or free market websites in Japan were surveyed in May-June 2023 by the authors, and 1157 MP product pages were examined. We found approximately 30-40% of the MP products were suspected to have potential legal risks in terms of their advertisements in their website descriptions, such as claiming pharmatheutical efficacy or describing pharmatheutical-like dosages. In addition, approximately 30-40% of the MP products also did not refer to cautions not to take MP products excessively because of the levodopa ingredients. Current study suggested the need of careful description of the MP products in the auction or free market websites for the MP products exhibitors or sellers, in order to fullfill legal requirements as well as to prevent MP abuse.
MeSH term(s)	Humans ; Levodopa/therapeutic use ; Mucuna ; Advertising ; Phytotherapy ; Japan ; Parkinson Disease/drug therapy ; Plant Extracts/therapeutic use
Chemical Substances	Levodopa (46627O600J) ; Plant Extracts
Language	Japanese
Publishing date	2023-10-13
Publishing country	Japan
Document type	English Abstract ; Journal Article
ZDB-ID	200514-1
ISSN	1347-5231 ; 0031-6903 ; 0372-7750 ; 0919-2085 ; 0919-2131
ISSN (online)	1347-5231
ISSN	0031-6903 ; 0372-7750 ; 0919-2085 ; 0919-2131
DOI	10.1248/yakushi.23-00145
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