ADVENTURES IN TARGETING

ABSTRACT

An overview of our experiences in the field of immunoliposomal anticancer drugs is provided with respect to choice of ligand, and choice of model system, in order to provide some guidance as to the rational use of this new technology. Liposomes targeted by either peptide or monoclonal antibodies showed significantly higher binding to their respective target cells in vitro compared to non-targeted liposomes in all model systems examined. This higher binding led to higher cytotoxicities relative to non-targeted liposomes. For the immunoliposomes to deliver their entrapped drug to target cell in vivo, long circulations half-lives are required. We have evaluated the pharmacokinetics of liposomes prepared by several different coupling techniques, and have found significant differences in the clearance of these immunoliposomes from the circulation. Immunoliposomes prepared with whole anti-CD19 IgG coupled by the Mal-PEG-DSPE method demonstrated a short plasma half-life, which may reflect the random orientation of the MAb on the liposome surface. Coupling methods that mask or eliminate the Fc region result in immunoliposomes that have clearance rates more similar to untargeted liposomes. Insertion of peptides or antibodies into pre-formed liposomes through incubation with ligand-coupled PEG micelles resulted in immunoliposomes, termed post-insertion liposomes, that demonstrated comparable in vitro binding, pharmacokinetic profiles and in vivo therapeutic efficacy to liposomes made by conventional coupling methods. The therapeutic efficacy of liposomes, prepared by various coupling methods and targeted by different ligands, was compared in several different animal models of either haematological malignancies, pseudometastatic disease or solid tumours. In our hands, successful in vivo targeting has been obtained when the target is either small or readily accessible from the vasculature, where the liposomes have longer circulating half-lives and/or where a ligand against an internalizing epitope has been chosen. These results should aid in the rational design of applications for immunoliposomal drugs in the future.     

THE TEMPERATURE CHARACTERISTIC FOR PHARYNGEAL BREATHING RHYTHM OF THE FROG

The frequency of the pharyngeal respiratory rhythm of frogs exhibits a critical thermal increment µ = 8,800 calories. At about 15° irregularities are apparent, which may be reduced by continued adaptation to room conditions. The frequency depends upon a process possibly synaptic in locus and apparently belonging among the group of respiratory reactions. Its temperature characteristic sharply separates this process from those reactions known to be catalyzed by H ion.     

有关节肢动物系统发育若干问题的研究进展

近年来对节肢动物系统发育问题的认识有了相当大的变化,尤其是支序分析研究方法的使用,以及来自分子系统学和分子发育生物学的证据,成为继比较形态学之后有力的研究手段,近年来的研究显示线虫,缓步类和有爪类是节肢动物的近缘类群,而非以前绝大多数学者所认为的软体动物的环节动物,对于节肢动物门的单系性及其内部类群间关系的问题,目前倾向于认为（1）节肢动物为单系群;（2）由甲壳类,六足类和多足类联合形成单系群－具颚类;（3）与六足类分子系统学两方面研究的支持;对第3点的争议虽较大,但就论据而言确为优势观点。     

紫杉类化合物研究进展

自本世纪70年代从欧洲红豆杉树皮中提取分离得到具有抗癌活性的天然产物紫杉醇以来,关于红豆杉属植物的研究已取得了许多进展。本文就1990年以后发表的有关文献。对该属植物的化学成分研究、合成方法、细胞培养技术及构效关系研究进行综述。     

CRITICAL INCREMENT FOR OPERCULAR BREATHING RHYTHM OF THE GOLDFISH

The temperature characteristic for opercular breathing rhythm in the quiescent goldfish is 16,500 calories. The reactions governing the frequency of breathing movements in vertebrates appear to be constituent links in the oxidative metabolism of the controlling cells.     

SELECTIVITY IN THE STUDY OF THE CARDIOVASCULAR SYSTEM

The principle of selectivity in the roentgenology of the cardiovascular system is now firmly established. The chambers of the heart and certain vascular beds lend themselves admirably to selective catheter or needle study, without the necessity of perfusing large segments of the cardiovascular bed which are irrelevant to a particular study.A technique of percutaneous transfemoral selective ciné coronary arteriography has been developed and applied to clinical subjects. Nevertheless, selectivity has specific limitations, and the use of the selective versus the nonselective approach must be weighed in each case, with the status of the patient as well as the requirements of the diagnostic investigation taken into account in reaching a decision.     

中国涡虫纲分类学研究进展

涡虫纲在分类学上归属于扁形动物门(Platyhelminthes),本纲动物主要生活在淡水和海洋,少数生活于潮湿的土壤中,多营自由生活,少数为共生或寄生生活.在动物演化的历史进程中,扁形动物的出现,标志着动物界的演化发展已开始由水生向陆生、由固着或漂浮生活向自由爬行生活过渡,并相应在形态上演化出一系列发展水平上关键性的变化,因此在动物进化中占有重要地位;由于它们对水质变化十分敏感,因此是一类很好的水体污染的指示动物;同时,由于其再生能力特别强,因而又是研究细胞分化与脱分化分子机理的好材料,百年来一直是国际动物界热衷探索的研究领域.遗憾的是,我国动物学界从事涡虫研究者甚少,过去属于空白或薄弱学科.本文对我国涡虫纲研究的历史与现状进 行全面概述,以期为我国涡虫纲的区系分类研究提供全面详实的资料.       

ON THE TEMPERATURE CHARACTERISTICS FOR FREQUENCY OF BREATHING MOVEMENTS IN INBRED STRAINS OF MICE AND IN THEIR HYBRID OFFSPRING. I

Young mice of a selected line of the dilute brown strain of mice exhibit over the range 15–25°C. (body temperature) a relation of frequency of breathing movements to temperature such that when fitted by the Arrhenius equation the data give a value for the constant µ of 24,000± calories or, less frequently, 28,000±. Young mice of an inbred albino strain show over the range 15–20°C. a value of µ = 34,000±, or, less frequently, 14,000±, with a critical temperature at about 20°C. and a value of µ = 14,000± above 20°C. The F₁ hybrids of these two strains, and the backcross generations to either parent strain, exhibit only those four values of the temperature characteristic observed in the parent strains and none other. One may therefore speak of the inheritance of the value of the constant µ, but the inheritance shows in this instance no Mendelian behavior. Furthermore there appears to be inherited the occurrence (or absence) of a critical temperature at 20°C. These experiments indicate the "biological reality" of the temperature characteristics.     

庞泉沟保护区核心区植被景观类型特征研究

利用植被景观类型图,获得面积、周长、景观斑块的长、宽等信息,对庞泉沟保护区核心区的植被景观特征进行分析。结果表明,核心区景观及斑块分布具有明显的地带性;核心区景观多样性较小,均匀度较低。另外,本文尝试用长宽比、伸张度、圆环度和周长与长轴的比这四种指数对景观斑块的特征进行了分析。结果表明,这四种指数在景观特征分析中具有一定的生态学意义。     

THE SIGNIFICANCE OF THE CAMBIUM IN THE STUDY OF CERTAIN PHYSIOLOGICAL PROBLEMS

1. The adjacent, undifferentiated, uninucleated cells of the lateral meristem or cambium are of two distinct shapes and sizes: (1) small, more or less isodiametric initials which are of the same general order of magnitude as the cells of the terminal meristem and embryo; and (2) large, elongated initials which in certain cases may attain a length of more than 10,000 micra and a volume of 10,000,000 cubic micra. The large initials may be induced to divide to form small initials, and the latter to regenerate elongated cells of normal dimensions. Thus, the cambium affords an unusually favorable medium for the study of a number of fundamental physiological and cytological problems. 2. A study of the cambium reveals the fact that there is a very-much greater variability in the size of meristematic cells in plants than was suspected by Sachs or Strasburger, and that the working sphere of the nucleus is by no means so restricted as assumed by these investigators. 3. Although the larger cambial initials of Pinus strobus tend to have larger nuclei, the nucleocytoplasmic-relation varies within wide limits and the diploid number of chromosomes is constant. The conditions in the cambium do not support Winkler''s view that there is a close correlation between chromosomal number (chromosomal mass) and cell size in the somatic tissue of plants, and that giant cells are hyperchromatic. 4. The process of cell plate formation in the cambium is a remarkable phenomenon, and one which is significant in discussing the relative merits of various theories concerning the dynamics of karyokinesis and cytokinesis. 5. The newly formed partition membranes in the cambial initials frequently intersect the side walls at angles of varying degrees of acuteness, which is in contradiction to Errera''s (Plateau''s) Law of Minimal Area.     

襀翅目化石的研究进展

回顾中国及世界襀翅目化石研究进展,列出已发表的化石种类名录、分布及年代,共19科、85属、225种;襀翅目化石世界分布,但主要集中在前苏联地区,中国仅14种.不同地质年代发现的襀翅目种类、数量和特征不同.本文并简要介绍稚虫食性、系统学、古地理和古生态等方面的研究成果,并初步分析了研究中存在的一些问题和今后需要解决的问题.     

蛋白质-蛋白质对接中打分函数的研究

通过分析蛋白质－蛋白质间的静电、疏水作用和熵效应与相对于晶体结构的蛋白质主链原子的均方根偏差（RMSD）的相关性,定量地考查了它们在蛋白质－蛋白质对接中作为打分函数评价近天然构象的能力。对7个蛋白质复合物体系的分析表明,就水化能而言,原子接触势模型（ACE）优于原子水化参数模型（ASP）,且修正的ACE模型具有更好的评价近天然构象的能力;水化能与静电能结合对评价能力有进一步的提高。最后,我们将静电和修正的ACE水化能结合作为打分函数用于36个蛋白质复合物体系的对接研究,进一步证实了这两种能量项的组合能有效地将近天然结构从分子对接模式中区分出来。