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Jikken dobutsu. Experimental animals最新文献

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Educationnal Seminar Educationnal研讨会
Pub Date : 2019-07-31 DOI: 10.1538/expanim.68suppl-ES
T. Okamura
Pain in laboratory animals is a major animal welfare problem that must be addressed. Research procedures using laboratory animals should be refined to minimize pain and distress. General anesthesia is produced using either injectable or inhalational agents, or a combination of the two methods. Balanced anesthesia is the technic in which a number of different agents are combined to produce a desired effect. Anesthetic agents can be given to produce all of these required features of general anesthesia: loss of consciousness, analgesia, muscle relaxation and suppression of reflex activity. Understanding of the pharmacological features of anesthetic agents, managing and monitoring anesthesia, post-operative care and pain assessment are necessary to protect the laboratory animals from the pain and stress of surgical intervention. In this talk, we will discuss which methods are more appropriate to minimize the pain and distress associated with the experimental procedures.
实验动物的疼痛是一个必须解决的主要动物福利问题。使用实验动物的研究程序应加以改进,以尽量减少疼痛和痛苦。全身麻醉可以使用注射或吸入药物,也可以使用两种方法的结合。平衡麻醉是一种技术,其中许多不同的药物组合,以产生预期的效果。麻醉药物可以产生全麻所要求的所有特征:意识丧失、镇痛、肌肉松弛和反射活动抑制。了解麻醉药物的药理特性,管理和监测麻醉,术后护理和疼痛评估是必要的,以保护实验动物免受手术干预的疼痛和应激。在这次演讲中,我们将讨论哪种方法更适合最小化与实验过程相关的疼痛和困扰。
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引用次数: 0
Plenary Lecture 2 全体讲座2
Pub Date : 2019-07-31 DOI: 10.1538/expanim.68suppl-PL2
Yoshihiro Kawaoka
Every year, influenza epidemics occur, causing increased morbidity and mortality, particularly in vulnerable populations, such as the very young and very old. In addition, worldwide epidemics, such has the 1918 pandemic, occasionally occur. Consequently, influenza has an enormous impact on the global economy. By contrast, Ebola virus has only been recognized since 1976, and, until recently, outbreaks of this virus had caused relatively few deaths because they occurred in rural, isolated areas. However, the recent outbreak in West Africa occurred over a large, densely populated urban area and changed our understanding of what constitutes an Ebola virus outbreak. I will discuss our recent research on these viruses. The 66th Annual Meeting of Japanese Association for Laboratory Animal Science
每年都发生流感疫情,造成发病率和死亡率上升,特别是在脆弱人群中,如幼童和老年人中。此外,像1918年大流行这样的世界性流行病偶尔也会发生。因此,流感对全球经济产生了巨大影响。相比之下,埃博拉病毒直到1976年才被确认,而且直到最近,这种病毒的爆发造成的死亡人数相对较少,因为它们发生在偏远的农村地区。然而,最近在西非爆发的疫情发生在一个人口稠密的大型城市地区,改变了我们对什么是埃博拉病毒爆发的理解。我将讨论我们最近对这些病毒的研究。第66届日本实验动物科学协会年会
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引用次数: 1
Symposium 3 研讨会3
Pub Date : 2019-07-31 DOI: 10.1538/expanim.68suppl-S3
Tomoji Mashimo
Humanized mouse in which human cells and tissues are engrafted and functioned in the mice is an important tool to mimic human physiology for biomedical and drug discovery researches. Although rodent models are generally used in preclinical studies investigating the efficacy and safety of novel drugs, they do not accurately evaluate the drug properties due to the species barrier. Non-human primates are valuable models for human diseases compared to rodents, but it is costly and requires a special breeding facility with expert for handling under strict ethical regulations. Severe combined immunodeficient NOG or NSG mice were developed independently in 2002 at CIEA or in 2005 at Jackson Laboratory. These mice exhibited multiple immunodeficiency lacking T, B and NK cells and functional defect of other innate immune cells. Therefore, the NOG or NSG mice have enabled high engraftment of primary human cells or tissues and to differentiate human T and B cells after human hematopoietic stem cell transplantation. However, human innate immune cells including NK cells, macrophages, granulocytes, mast cells, etc. do not fully differentiated in them. We aim to establish the next generation humanized mice in which various human cytokine genes are introduced to analyze human hematopoietic and immune systems and to develop human immune disease models. In the symposium, I provide an overview of the recent advances in humanized mouse technologies and applications for drug discovery in preclinical researches. The 66th Annual Meeting of Japanese Association for Laboratory Animal Science
将人类细胞和组织移植并在小鼠体内发挥作用的人源化小鼠是生物医学和药物发现研究中模拟人类生理学的重要工具。尽管啮齿动物模型通常用于研究新药疗效和安全性的临床前研究,但由于物种屏障的原因,它们不能准确评估药物特性。与啮齿类动物相比,非人类灵长类动物是人类疾病的宝贵模型,但成本高昂,需要一个特殊的繁殖设施,由专家根据严格的道德规范进行处理。严重联合免疫缺陷NOG或NSG小鼠于2002年在CIEA或2005年在Jackson实验室独立开发。这些小鼠表现出缺乏T、B和NK细胞的多重免疫缺陷以及其他先天免疫细胞的功能缺陷。因此,NOG或NSG小鼠已经实现了原代人类细胞或组织的高植入,并在人类造血干细胞移植后分化人类T和B细胞。然而,包括NK细胞、巨噬细胞、粒细胞、肥大细胞等在内的人类先天免疫细胞在其中没有完全分化。我们的目标是建立下一代人源化小鼠,在其中引入各种人类细胞因子基因来分析人类造血和免疫系统,并开发人类免疫疾病模型。在研讨会上,我概述了人源化小鼠技术的最新进展以及药物发现在临床前研究中的应用。第66届日本实验动物科学协会年会
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引用次数: 1
International Award Lecture 国际奖讲座
Pub Date : 2019-07-31 DOI: 10.1538/expanim.68suppl-IA
N. Zainal, J. Chai, B. Lye, Phei Gan, N. Zulaziz, Chuan Wang, V. Sutavani, C. Ottensmeier, E. King, G. Thomas, N. Savelyeva, S. Cheong, K. Lim
Lack of effective therapies remains the biggest problem in the treatment of head and neck cancer (HNC). More recently, antibodies targeting the immune checkpoint molecule (anti-PD1) have been developed and approved for HNC. Although the clinical activity of PD1 inhibitors is promising, most patients remain unresponsive to this therapy with objective response rates of less than 20%. Additionally, emerging data is demonstrating that a significant subset of patients who initially responded to immune checkpoint inhibitors eventually relapsed after a period of response. One of the strategies to boost the immune response from immunotherapies is combining the immune checkpoint inhibitor with a tumor-associated antigen (TAA) vaccine. This will potentially lead to the generation of antigen-specific immune response that is more durable in eradicating cancer cells in patients. We have previously identified two immunogenic TAAs that were highly expressed in HNC patients. This has led to the generation of a DNA vaccine that incorporates the full-length DNA sequences of the two TAAs (DV). The objective of our study was to determine the preclinical efficacy of DV in combination with anti-PD1 by comparing tumor growth, survival, and immune profile in mice. As syngeneic HNSCC models are limited, we used a well characterized B16/F10 melanoma model that has been widely used for immunotherapy studies and is susceptible to checkpoint inhibitors including PD1 antibody. The B16/F10 is transfected with human HLA-A2, and the two target TAA constructs to mimic the expression of these antigens in HNC. This cell line was inoculated subcutaneously into a transgenic mouse model (B6.Cg-Tg(HLA-A/H2-D)2Enge/J) that carried a chimeric HLA-A2. Anti-PD1 treatment was given intraperitoneally at the lower abdomen every 3 days starting from day 3 post-cell inoculation and DV vaccination was performed intramuscularly at both thigh muscles on days 5 and 26 postcell inoculation. Tumor measurements were made every 3-4 days. Upon termination, spleen and tumor were harvested to study the presence of immune activation. We discovered that when DV and anti-PD1 were used as a combination, a significant tumor control is achieved as compared to single treatment and control groups, indicating a synergistic effect of DV with anti-PD1. Additionally, prolonged survival was observed in mice from the combination group. Noteworthy, the combination treated animals showed an increased in antigen-specific responses by the ELISPOT assay, suggesting the tumor control and prolonged survival is due to antigen-specific immune responses. In conclusion, the use of DV and anti-PD1 has shown great potential in the combinatorial approach of immunotherapeutic, in which the two agents work synergistically in controlling tumor growth in mice model.
缺乏有效的治疗仍然是头颈部癌症(HNC)治疗的最大问题。最近,针对免疫检查点分子(抗PD1)的抗体已经被开发出来并被批准用于HNC。尽管PD1抑制剂的临床活性很有希望,但大多数患者对这种治疗仍然没有反应,客观反应率低于20%。此外,新出现的数据表明,最初对免疫检查点抑制剂有反应的患者中,有相当一部分在一段时间后最终复发。增强免疫疗法免疫反应的策略之一是将免疫检查点抑制剂与肿瘤相关抗原(TAA)疫苗相结合。这可能会导致产生抗原特异性免疫反应,这种反应在根除患者癌症细胞方面更持久。我们之前已经鉴定了两种在HNC患者中高度表达的免疫原性TAA。这导致了DNA疫苗的产生,该疫苗结合了两种TAA(DV)的全长DNA序列。我们研究的目的是通过比较小鼠的肿瘤生长、存活率和免疫状况来确定DV与抗PD1联合使用的临床前疗效。由于同基因HNSCC模型有限,我们使用了一种特征良好的B16/F10黑色素瘤模型,该模型已广泛用于免疫治疗研究,对包括PD1抗体在内的检查点抑制剂敏感。B16/F10用人HLA-A2和两种靶向TAA构建体转染以模拟这些抗原在HNC中的表达。将该细胞系皮下接种到携带嵌合HLA-A2的转基因小鼠模型(B6.Cg-Tg(HLA-a/H2-D)2Enge/J)中。从细胞接种后第3天开始,每3天在小腹腹膜内给予抗PD1治疗,并在细胞接种后的第5天和第26天在大腿两侧肌肉内进行DV疫苗接种。每3-4天进行一次肿瘤测量。终止后,采集脾脏和肿瘤以研究免疫激活的存在。我们发现,当DV和抗PD1联合使用时,与单一治疗组和对照组相比,实现了显著的肿瘤控制,表明DV与抗PD1的协同作用。此外,在来自组合组的小鼠中观察到延长的存活时间。值得注意的是,联合治疗的动物通过ELISPOT测定显示抗原特异性反应增加,这表明肿瘤控制和延长生存期是由于抗原特异性免疫反应。总之,DV和抗PD1的使用在免疫治疗的组合方法中显示出巨大的潜力,在该方法中,两种药物协同控制小鼠模型中的肿瘤生长。
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引用次数: 0
Symposium 4 研讨会4
Pub Date : 2019-07-31 DOI: 10.1538/expanim.68suppl-S4
Hideaki Morishita, Norito Tamura, Yuki Kanda, Yuriko Sakamaki, N. Mizushima
The discovery of Autophagy-related genes (ATGs) by Dr. Yoshinori Ohsumi opened the door to solve the molecular mechanisms of autophagy. But, the research on autophagy does not still mature, rather it contains a large number of issues that should be addressed. To date, a series of ATG genes has been identified, but working mechanism of each ATG gene product remains unclear. Moreover, while growing lines of evidence shed light on the importance of unconventional mode of autophagy such as selective autophagy, the role in our life course is still a mystery. Further, while autophagy is considered to be involved in various vital events such as cellular differentiation, stem cell homeostasis and anti-aging, those regulatory mechanisms through autophagy are still not clear. In my talk, I show the role(s) of selective autophagy on transcriptional regulation and network. The 66th Annual Meeting of Japanese Association for Laboratory Animal Science
Yoshinori Ohsumi博士发现的自噬相关基因(autophagy -related genes, ATGs)为解决自噬的分子机制打开了大门。但是,自噬的研究还不成熟,还存在着大量需要解决的问题。迄今为止,已鉴定出一系列ATG基因,但各ATG基因产物的作用机制尚不清楚。此外,尽管越来越多的证据揭示了选择性自噬等非常规自噬模式的重要性,但其在我们生命过程中的作用仍然是一个谜。此外,虽然自噬被认为参与了细胞分化、干细胞稳态和抗衰老等多种生命事件,但自噬的调控机制尚不清楚。在我的演讲中,我展示了选择性自噬在转录调控和网络中的作用。第66届日本实验动物科学协会年会
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引用次数: 1
Plenary Lecture 1 全体讲座1
Pub Date : 2019-07-31 DOI: 10.1538/expanim.68suppl-PL1
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引用次数: 1
Congress Award Lecture 大会颁奖讲座
Pub Date : 2019-07-31 DOI: 10.1538/expanim.68suppl-L
○Masahide Asano, ○Takashi Inoue
I have been carrying out research mainly on carbohydrate chains and histone modifications both are posttranslational modifications. The former is called a glyco-code and the latter is called a histone-code, both are not determined by genetic code. My ultimate goal is to decode these two codes and solve the mystery of life science. In our glycobiology research, we focused on galactosyltransferases (β4GalTs), consist of seven genes, involved in producing various functional carbohydrate chains. At first, we generated a KO mouse of the β 4GalT-1 gene using homologous recombination method in ES cells. β4GalT-1 KO mouse showed growth retardation after birth, short-lived, abnormal growth and differentiation of skin and small intestinal epithelial cells (EMBO J, 1997). In β4GalT-1 KO mice, expression of sialyl Le, a selectin ligand, of inflammatory cells decreased and the skin inflammatory response was attenuated, and wound healing was delayed because β 4GalT-1 is involved in the synthesis of sialyl Le (Blood, 2003, Am J Pathol, 2004). Furthermore, β4GalT-1 KO mice spontaneously developed IgA nephropathy probably due to abnormal glycosylation of IgA (Am J Pathol, 2007). Next, β4GalT-2 KO mouse was prepared and found abnormalities in spatial learning memory and coordinated movements by behavioral experiments (JBC, 2009). When β 4GalT-5 KO mouse was prepared, it was lethal at the embryonic stage. It was found that β4GalT-5 is an enzyme synthesizing LacCer (Glycobiology, 2010). Furthermore, we generated a cranial nervous system-specific β4GalT-5 and -6 double KO mice, who showed ataxia and died by 3 weeks of age (PLoS Genetics, 2018). As described above, by preparing and analyzing four kinds of β4GalT KO mice, there is a clear division of roles among them, and the galactose chains have a wide variety of physiological functions. It is my great honor to be awarded the Ando-Tajima Prize of the JALAS. I would like to thank all the members of the JALAS, and express my sincere gratitude to all the staff, graduate students, and co-workers who have carried out these researches together. The 66th Annual Meeting of Japanese Association for Laboratory Animal Science
我主要研究的是碳水化合物链修饰和组蛋白修饰,它们都是翻译后修饰。前者称为糖密码,后者称为组蛋白密码,两者都不是由遗传密码决定的。我的最终目标是破解这两个密码,解开生命科学的奥秘。在糖生物学研究中,我们重点研究了半乳糖转移酶(β4GalTs),它由七个基因组成,参与产生各种功能碳水化合物链。首先,我们在胚胎干细胞中采用同源重组方法获得了β 4GalT-1基因的KO小鼠。β4GalT-1 KO小鼠出生后表现为生长迟缓,寿命短,皮肤和小肠上皮细胞生长分化异常(EMBO J, 1997)。在β4GalT-1 KO小鼠中,炎症细胞中选择素配体唾液酸Le的表达减少,皮肤炎症反应减弱,伤口愈合延迟,因为β4GalT-1参与唾液酸Le的合成(Blood, 2003, Am J Pathol, 2004)。此外,β4GalT-1 KO小鼠自发发生IgA肾病可能是由于IgA糖基化异常(Am J Pathol, 2007)。接下来,制备β4GalT-2 KO小鼠,通过行为实验发现空间学习记忆和协调运动异常(JBC, 2009)。β 4GalT-5 KO小鼠在胚胎期具有致死性。研究发现,β4GalT-5是一种合成LacCer的酶(Glycobiology, 2010)。此外,我们培育了颅神经系统特异性β4GalT-5和-6双KO小鼠,这些小鼠表现出共济失调,并在3周龄时死亡(PLoS Genetics, 2018)。如上所述,通过制备和分析四种β4GalT KO小鼠,它们之间的作用分工明确,半乳糖链具有多种多样的生理功能。我很荣幸被授予JALAS的安藤田岛奖。在此,我要感谢JALAS的所有成员,并向所有共同开展这些研究的工作人员、研究生和同事表示衷心的感谢。第66届日本实验动物科学协会年会
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引用次数: 0
Young Scientist Award 青年科学家奖
Pub Date : 2019-07-31 DOI: 10.1538/expanim.68suppl-Y
Linda Levine Madori
• Advancing perfection and perceiving remarkable commitments made by the youthful researchers for their work done essentially during the span of study. • Find out about career advancement and the most recent research devices and technologies in your field. • Graduates are motivated by the chance to choose neighbourhood or worldwide subjects of pertinence/enthusiasm to them and build up their own logical examinations and models drawing in locally or universally. • Two researchers will be chosen for the Awards. • Chance to be a student envoy. • Chances to coordinate with partners around the world • Discounts at the PULSUS conferences, at different worldwide venues in future. • Chance to distribute full length papers in rumoured supporting international journals of respective conference • Best Young Scientist Award introduction will be named by the board and in the event that they wish to publish the full-length paper, they can publish in supporting worldwide journals of the respective conference at free of preparing charges.
•促进完美和感知卓越的承诺,由年轻的研究人员为他们的工作基本上在研究期间完成。•了解你所在领域的职业发展和最新的研究设备和技术。•毕业生有机会选择对他们有针对性/热情的社区或全球主题,并建立自己的逻辑考试和模型,吸引当地或全球。•将选出两名研究人员获得该奖项。•成为学生特使的机会。•有机会与世界各地的合作伙伴进行协调•未来在全球不同地点参加PULSUS会议的折扣。•最佳青年科学家奖的介绍将由董事会命名,如果他们希望发表全文论文,他们可以在各自会议的支持国际期刊上免费发表论文。
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引用次数: 0
Plenary Lecture 3 全体讲座3
Pub Date : 2019-07-31 DOI: 10.1538/expanim.68suppl-PL3
Katsuhiko Hayashi
The germ cell lineage ensures the creation of new individuals, thereby perpetuating the genomic and epigenetic information across the generations. During germ cell development, biologically significant events such as meiosis and gametogenesis are tightly controlled and disorder of the events causes infertility and developmental arrest of the next generation. Generation of gametes from mouse pluripotent stem cells, such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), in culture is a key goal in developmental and reproductive biology. Such a culture system will provide a unique platform for elucidating the molecular mechanisms underlying gametogenesis. More practically, it may be an indefinite source for reproduction and preservation of animals. We recently established a culture system that induces functional mouse primordial germ cells (PGCs), origin of eggs and sperm, from ESCs/iPSCs. PGCs produced from ESCs/iPSCs are fully potent, since they differentiated into eggs and sperm by transplantation into ovary and testis, respectively, which in turn gave rise to healthy pups. Furthermore, we recently developed a culture system that reconstitutes the entire process of oogenesis from mouse pluripotent stem cells, yielding in vitro-generated eggs that gave rise to healthy offspring. In the lecture, I will introduce recent advances in reconstitution of germ cell development using ESCs/iPSCs, update current experiments to address molecular mechanisms underlying oogenesis and discuss a future direction of this technology. The 66th Annual Meeting of Japanese Association for Laboratory Animal Science
生殖细胞谱系确保了新个体的产生,从而使基因组和表观遗传信息代代相传。在生殖细胞发育过程中,减数分裂和配子体发生等生物学上的重要事件受到严格控制,这些事件的紊乱会导致下一代的不育和发育停滞。小鼠多能干细胞,如胚胎干细胞(ESCs)和诱导多能干细胞(iPSCs),在培养中产生配子是发育和生殖生物学的关键目标。这样的培养系统将为阐明配子体发生的分子机制提供一个独特的平台。更实际的是,它可能是动物繁殖和保护的无限来源。我们最近建立了一个培养系统,从ESCs/iPSCs中诱导功能小鼠原始生殖细胞(PGCs),卵子和精子的来源。由ESCs/iPSCs产生的PGCs是完全有效的,因为它们分别通过移植到卵巢和睾丸分化为卵子和精子,从而产生健康的幼崽。此外,我们最近开发了一种培养系统,该系统重建了小鼠多能干细胞的卵子发生的整个过程,在体外产生卵子,产生健康的后代。在讲座中,我将介绍利用ESCs/iPSCs重建生殖细胞发育的最新进展,更新当前的实验以解决卵子发生的分子机制,并讨论该技术的未来方向。第66届日本实验动物科学协会年会
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引用次数: 0
LAS Seminar 1 研讨会1
Pub Date : 2019-07-31 DOI: 10.1538/expanim.68suppl-LAS1
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引用次数: 0
期刊
Jikken dobutsu. Experimental animals
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