内分泌学百年回眸与未来

内分泌学作为20世纪初的一门新兴学科,百年来获得了长足的进展.北京协和医院在这一领域亦曾作出不少贡献.而近年来层出不穷的新技术为内分泌学领域的诊疗带来了新的突破.本文回顾了内分泌学的历史及北京协和医院在内分泌领域的贡献,并对学科的未来发展进行了深入思考.     

近二十年来植物分类学的进展

过去近二十年中,可以看到在植物分类学和系统学领域里,异常丰硕的成果和各种不同形式的活动。这些年在宏观系统学(macrosystematics)方面所获得的新资料和新的研究方法,充分说明这一领域的进展是令人鼓舞的。本文主要以Heywood的近著《植物分类学当前的景象》为蓝本,对这一领域的新发展和新动向作一简要回顾。至于     

2001年的分子生物学

在过去的十年里,分子生物学家在克服遗传转移障碍这一领域已取得一系列成就:不仅开发了cosmid克隆、植物的Ti质粒转染以及cDNA克隆等技术,而且扩展了电激法的适用     

纳米技术在生物医学领域的研究现状

纳米生物医学是纳米技术与现代生物医学技术结合的产物,近年来这一领域逐渐受到科学界和企业界的重视,得到了许多振奋人心的进展,具有广泛的应用前景。作者从纳米生物材料、纳米载体、医学诊断和纳米治疗技术四个方面讨论了纳米技术在医学领域的研究现状,希望为读者展现这一新生领域的巨大潜力。     

在回顾中增强信心与力量

在回顾中增强信心与力量徐有恒编者按徐有恒教授是我国的血液生理学家。他继承了著名老生理学家易见龙先生的优良传统，兢兢业业，执着追求，在造血生理学这一领域的研究中，做出显著成绩。他还在“双肩挑”方面，为我们作出表率。承《生理科学进展》编辑部约我写一篇刊头...     

DNA水平上的植物系统学研究方法

本文简要总结了近年来在ＤＮＡ水平上的植物系统学研究方法,着重介绍了限制性长度多态性分析,ＰＣＲ技术在植物系统学上的应用等这一领域最新的进展,并对分子数据的分析方法及系统树的构建进行了详细讨论。     

朊病毒研究进展

长期以来,对传染性海绵状脑病(transmissible spongiform encephalopathies,TSEs)病原因子的本质没有共识.曾提出种种假说,诸如肉孢子虫说、滤过性病毒说、慢病毒说和非寻常病毒说等.直至1982年,Prusiner等获得部分纯化的搔痒病(scrapie)病原因子提出朊病毒假说[1],才取得实质性进展.近十几年,朊病毒研究取得了突破性进展,逐渐得到认同.Prusiner也因这一领域的杰出贡献荣获1997年度诺贝尔医学奖.本文拟对这方面的进展作简要复习.     

植物基因打靶研究进展

植物基因打靶研究的重心在于研究如何使基因打靶成为植物基因操作的常规手段。近年来科学工作者在这一领域取得了突破性进展,这些成就主要依托锌指核酸酶,染色质重建蛋白以及正负选择的应用。对上述成果进行综述,并对其发展趋势进行展望。     

分子标记技术在灵长类繁殖行为研究中的应用——应用

分子标记(Molecular Marker)技术在这一领域中的应用主要集中于动物的性选择策略、交配策略、繁殖成功度等方面的研究.作为自然选择进化论的中心机理,种内的繁殖竞争一直是行为生物学最为关注的焦点之一[1～2].近年来关于灵长类繁殖行为一个引人入胜的主题就是优势等级(Dominance Rank)与繁殖成功率(Reproductive Success)相关性的探讨.     

国外动态

欧洲议会反对克隆人类早期胚胎欧洲议会 9月 7日在法国斯特堡举行的会议上 ,以 2 37票赞成、2 30票反对和 4 3票弃权的表决结果 ,通过了一项不支持克隆人类早期胚胎的决议。决议指出 ,以医疗为目的而克隆人类早期胚胎的“治疗性克隆”研究 ,将不可避免地超出合理的研究界限。决议说 ,欧洲议会认为 ,除了“治疗性克隆”外 ,科学家们应该能够找到其它的方法来医治严重疾病。这项不具约束性的决议还认为 ,欧盟不应为“治疗性克隆”提供任何研究资助。决议还呼吁英国政府要重新考虑其在“治疗性克隆”问题上的立场。今年 8月 16日 ,英国政府首席…     

Biotechnology in reproductive medicine

In this review I am summarizing the past and current progress in the field of pharmaceutical, diagnostic, therapeutic, and reproductive cloning in mammals. Several human gene products can be pharmaceutically explored in transgenic farm animals and employed for medical applications. Preimplantation genetic diagnosis (PGD) is utilizing modern molecular cloning techniques to detect genetic and chromosomal aberrations in early embryos originating from patients with inborn errors at risk for hereditary diseases or age-related risk for abnormal karyotype. Stem cell engineering from early human embryos is creating new and promising but also controversial applications for therapeutic and regenerative medicine. Potential risk factors for reproductive cloning are presented and discussed in the context of possible developmental malformations, frequently observed after embryo culture and cloning in farm animals. Future extension of biotechnology to human reproductive cloning is currently under worldwide dispute.     

Prospects for the use of nuclear transfer in human transplantation

The successful application of nuclear transfer techniques to a range of mammalian species has brought the possibility of human therapeutic cloning significantly closer. The objective of therapeutic cloning is to produce pluripotent stem cells that carry the nuclear genome of the patient and then induce them to differentiate into replacement cells, such as cardiomyocytes to replace damaged heart tissue or insulin-producing beta cells for patients with diabetes. Although cloning would eliminate the critical problem of immune incompatibility, there is also the task of reconstituting the cells into more complex tissues and organs in vitro. In the review, we discuss recent progress that has been made in this field as well as the inherent dangers and scientific challenges that remain before these techniques can be used to harness genetically matched cells and tissues for human transplantation.     

核移植与治疗性克隆

核移植与治疗性克隆在畜牧业生产以及生物医学上具有广阔和诱人的应用前景。文章分析指出卵母细胞质量与供核细胞重新编程是影响体细胞核移植效率及克隆动物异常的主要因素,阐述了治疗性克隆所面临的一些基本问题及出路：治疗性克隆以核移植技术为基础,核移植所面临的一些问题也直接影响着治疗性克隆的临床应用;核移植胚胎干细胞分离培养效率的高低以及向重要功能细胞定向分化是治疗性克隆的前提;成体干细胞可用于一些重大疾病的治疗,但不能完全替代克隆性治疗;伦理问题也阻碍治疗性克隆的发展。核移植及治疗性克隆技术要想尽快更好地应用于临床和造福于人类,需要不断完善各技术环节和加强一些基础理论的研究。Abstract: Nuclear transfer and therapeutic cloning have widespread and attractive prospects in animal agriculture and biomedical applications. We reviewed that the quality of oocytes and nuclear reprogramming of somatic donor cells were the main reasons of the common abnormalities in cloned animals and the low efficiency of cloning and showed the problems and outlets in therapeutic cloning, such as some basic problems in nuclear transfer affected clinical applications of therapeutic cloning. Study on isolation and culture of nuclear transfer embryonic stem (ntES) cells and specific differentiation of ntES cells into important functional cells should be emphasized and could enhance the efficiency. Adult stem cells could help to cure some great diseases, but could not replace therapeutic cloning. Ethics also impeded the development of therapeutic cloning. It is necessary to improve many techniques and reinforce the research of some basic theories, then somatic nuclear transfer and therapeutic cloning may apply to agriculture reproduction and benefit to human life better.     

Galectin-3 is a new MerTK-specific eat-me signal

Phagocytosis of apoptotic cells and cellular debris is a critical process of maintaining tissue and immune homeostasis. Defects in the phagocytosis process cause autoimmunity and degenerative diseases. Phagocytosis ligands or "eat-me" signals control the initiation of the process by linking apoptotic cells to receptors on phagocyte surface and triggering signaling cascades for cargo engulfment. Eat-me signals are traditionally identified on a case-by-case basis with challenges, and the identification of their cognate receptors is equally daunting. Here, we identified galectin-3 (Gal-3) as a new MerTK ligand by an advanced dual functional cloning strategy, in which phagocytosis-based functional cloning is combined with receptor-based affinity cloning to directly identify receptor-specific eat-me signal. Gal-3 interaction with MerTK was independently verified by co-immunoprecipitation. Functional analyses showed that Gal-3 stimulated the phagocytosis of apoptotic cells and cellular debris by macrophages and retinal pigment epithelial cells with MerTK activation and autophosphorylation. The Gal-3-mediated phagocytosis was blocked by excessive soluble MerTK extracellular domain and lactose. These results suggest that Gal-3 is a legitimate MerTK-specific eat-me signal. The strategy of dual functional cloning with applicability to other phagocytic receptors will facilitate unbiased identification of their unknown ligands and improve our capacity for therapeutic modulation of phagocytic activity and innate immune response.     

哺乳动物体细胞核移植研究进展

体细胞核移植技术已经在基础研究领域与产业化应用领域体现出了重要的价值,因而体细胞核移植技术及其相关研究已经成为了生物领域的持续性研究热点,但是围绕体细胞核移植技术仍然存在许多质疑,其中最主要的就是体细胞核移植的效率较低。尽管如此,体细胞核移植研究仍然在近年来取得了令人瞩目的成就,包括小鼠与恒河猴核移植胚胎干细胞系的建立。该文就体细胞核移植的研究历史与进展进行简要的论述,同时针对体细胞核移植研究中的细胞重编程与治疗性克隆研究中的发展与问题进行剖析,希望能够积极推动治疗性克隆的研究进展,加速核移植与干细胞技术在产业化领域中的应用。     

A general cloning strategy for divergent plant cytochrome P450 genes and its application in Lolium rigidum and Ocimum basilicum

The investigation of plant cytochrome P450 genes and enzymes is a field of growing interest. Apparently, an even greater diversity of cytochrome P450 genes exists in plants in comparison to other eukaryotes. This may be due to their role in the biosynthesis of secondary metabolites that are present in plants in an enormous variety. Most cloning approaches are hampered by the large sequence diversity of plant cytochrome P450 genes. We present a method to clone divergent cytochrome P450 ESTs by a nested RT-PCR-strategy. These ESTs were used for the subsequent cloning of the corresponding full-size cDNAs of divergent families via cDNA-library screening. Sixteen cytochrome P450 genes belonging to different cytochrome P450-families have been identified in this way, proving the efficacy of the strategy. Received: 1 December 2000 / Accepted: 26 February 2001     

Language and values in the human cloning debate: a web-based survey of scientists and christian fundamentalist pastors

Over the last seven years, a major debate has arisen over whether human cloning should remain legal in the United States. Given that this may be the ‘first real global and simultaneous news story on biotechnology’ (Einsiedel et al., 2002, p. 313), nations around the world have struggled with the implications of this newly viable scientific technology, which is often also referred to as somatic cell nuclear transfer. Since the successful cloning of Dolly the sheep in 1997, and with increasing media attention paid to the likelihood of a successful human reproductive clone coupled with research suggesting the medical potential of therapeutic cloning in humans, members of the scientific community and Christian fundamentalist leaders have become increasingly vocal in the debate over U.S. policy decisions regarding human cloning (Wilmut, 2000). Yet despite a surfeit of public opinion polls and widespread opining in the news media on the topic of human cloning, there have been no empirical studies comparing the views of scientists and Christian fundamentalists in this debate (see Evans, 2002a for a recent study of opinion polls assessing religion and attitudes toward cloning).

In order to further investigate the values that underlie scientists' and Christian fundamentalist leader's understanding of human cloning, as well as their differential use of language in communicating about this issue, we conducted an open-ended, exploratory survey of practicing scientists in the field of molecular biology and Christian fundamentalist pastors. We then analyzed the responses from this survey using qualitative discourse analysis. While this was not necessarily a representative sample (in quantitative terms, see Gaskell & Bauer, 2000) of each of the groups and the response rate was limited, this approach was informative in identifying both commonalities between the two groups, such as a focus on ethical concerns about reproductive cloning and the use of scientific terminology, as well as significant differences including concerns over ‘playing God’ for the Christian pastors, focus on therapeutic cloning by scientists, and subtle but informative differences between the two groups in their use of scientific terminology and their interpretations of human cloning as scientific progress.     

Language and values in the human cloning debate: a web-based survey of scientists and Christian fundamentalist pastors

Over the last seven years, a major debate has arisen over whether human cloning should remain legal in the United States. Given that this may be the 'first real global and simultaneous news story on biotechnology' (Einsiedel et al., 2002, p.313), nations around the world have struggled with the implications of this newly viable scientific technology, which is often also referred to as somatic cell nuclear transfer. Since the successful cloning of Dolly the sheep in 1997, and with increasing media attention paid to the likelihood of a successful human reproductive clone coupled with research suggesting the medical potential of therapeutic cloning in humans, members of the scientific community and Christian fundamentalist leaders have become increasingly vocal in the debate over U.S. policy decisions regarding human cloning (Wilmut, 2000). Yet despite a surfeit of public opinion polls and widespread opining in the news media on the topic of human cloning, there have been no empirical studies comparing the views of scientists and Christian fundamentalists in this debate (see Evans, 2002a for a recent study of opinion polls assessing religion and attitudes toward cloning). In order to further investigate the values that underlie scientists' and Christian fundamentalist leader's understanding of human cloning, as well as their differential use of language in communicating about this issue, we conducted an open-ended, exploratory survey of practicing scientists in the field of molecular biology and Christian fundamentalist pastors. We then analyzed the responses from this survey using qualitative discourse analysis. While this was not necessarily a representative sample (in quantitative terms, see Gaskell & Bauer, 2000) of each of the groups and the response rate was limited, this approach was informative in identifying both commonalities between the two groups, such as a focus on ethical concerns about reproductive cloning and the use of scientific terminology, as well as significant differences including concerns over 'playing God' for the Christian pastors, focus on therapeutic cloning by scientists, and subtle but informative differences between the two groups in their use of scientific terminology and their interpretations of human cloning as scientific progress.     

Therapeutic cloning in individual parkinsonian mice

Cell transplantation with embryonic stem (ES) cell progeny requires immunological compatibility with host tissue. 'Therapeutic cloning' is a strategy to overcome this limitation by generating nuclear transfer (nt)ES cells that are genetically matched to an individual. Here we establish the feasibility of treating individual mice via therapeutic cloning. Derivation of 187 ntES cell lines from 24 parkinsonian mice, dopaminergic differentiation, and transplantation into individually matched host mice showed therapeutic efficacy and lack of immunological response.     

The ethics of therapeutic and reproductive human cloning.

Neither therapeutic cloning nor reproductive cloning necessarily pose insurmountable ethical obstacles. Two defences of therapeutic cloning are considered. The first defence, the argument from property, is rejected because it entails morally counter-intuitive consequences. We should prefer a 'balance of reasons' defence which leaves room for the view that human life has intrinsic value. Reproductive cloning is best defended by an appeal to the right to procreative autonomy. The sorts of harms it is feared clones will suffer are also suffered by children conceived through natural means, even when these harms were preventable. The right to reproductive autonomy disallows state control of any form of reproduction for the reasons of child welfare discussed.