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Researches on chemical carcinogens and mechanism of chemical carcinogenesis. Di-region theory--a quantitative molecular orbital model of carcinogenic activity for polycyclic aromatic hydrocarbons. 化学致癌物及化学致癌机制的研究。双区理论——多环芳烃致癌活性的定量分子轨道模型。
Pub Date : 1980-04-01
D Qianhuan

In this paper, we prove by perturbational molecular orbital (PMO) theory that with polycyclic aromatic hydrocarbons (PAH) there exist two regions having electrophilic activity, which are the necessary and sufficient condition for its carcinogenic activity. We are the first to obtain a quantitative equation for the carcinogenic activity of PAH, using the carbonium ion delocalization energies as parameters. By using the equation, the calculated carcinogenic activity is in fair accord with the experiment, and the consistent ratio comes up to 98%. Further study shows that the optimum distance for carcinogenic activity approximates to 2.80 A. This is just the distance between the negative centers in DNA double helix. Therefore, the key step of the carcinogenesis for PAH in vivo is the interstrand cross linkage between the DNA complementary base pair. In terms of this deduction, we suggest that the possible mechanism of chemical carcinogenesis should be a complementary frameshift mutation between the DNA double helix. We name such an idea "di-region theory", which probably might be of general significance for other chemical carcinogenesis.

本文用微扰分子轨道理论证明了多环芳烃(PAH)存在两个具有亲电活性的区域,这是其具有致癌性的充分必要条件。我们首次以碳离子离域能为参数,得到了多环芳烃致癌活性的定量方程。计算所得的致癌活性与实验结果吻合较好,符合率达98%。进一步研究表明,致癌活性的最佳距离约为2.80 A。这就是DNA双螺旋负中心之间的距离。因此,多环芳烃在体内致癌的关键步骤是DNA互补碱基对之间的链间交叉连锁。根据这一推论,我们认为化学致癌的可能机制应该是DNA双螺旋之间的互补移码突变。我们将这种观点称为“双区理论”,这可能对其他化学致癌作用具有普遍意义。
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引用次数: 0
The nature of the RNA products synthesized in vitro with a cell-free extract from TMV-infected tobacco leaves. 从受 TMV 感染的烟草叶片中提取的无细胞提取物在体外合成的 RNA 产物的性质。
Pub Date : 1980-03-01
F Rongxiang, W Xiaofeng, Q Bingyi, C Faxing, B Ming

A cell-free extract containing TMV-RNA replicase was prepared from TMV-infected tobacco leaves. It could synthesize double-stranded RNAs in the presence of four nucleoside triphosphates (among them, UTP was tritium-labelled), magnesium ion and actinomycin D. It was confirmed by polyacrylamide-agarose gel electrophoresis, RNase treatment, thermal denaturation and self annealing that 3H-ds RNAs, obtained from phenol-SDS extraction and Serva cellulose column chromatography, consisted of replicative form (RF) and replicative intermediate (RI) of TMV-RNA, with molecular weights of 40 X 10(6) and 5.0 X 10(6), respectively. Molecular hybridization competition experiment showed that 60-70% of the nascent RNAs in the 3H-ds RNA were plus strand of tMV-RNA.

从受 TMV 感染的烟草叶片中制备了含有 TMV-RNA 复制酶的无细胞提取物。它能在四种核苷三磷酸(其中UTP为氚标记)、镁离子和放线菌素D存在下合成双链RNA。通过聚丙烯酰胺-琼脂糖凝胶电泳、RNase处理、热变性和自退火证实,经酚-SDS提取和Serva纤维素柱层析得到的3H-ds RNA由TMV-RNA的复制形式(RF)和复制中间体(RI)组成,分子量分别为40 X 10(6)和5.0 X 10(6)。分子杂交竞争实验表明,3H-ds RNA 中 60-70% 的新生 RNA 为 tMV-RNA 的加链。
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引用次数: 0
Establishment of three human liver carcinoma cell lines and some of their biological characteristics in vitro. 三种人肝癌细胞系的建立及其体外生物学特性研究。
Pub Date : 1980-02-01
R Chen, D Zhu, X Ye, D Shen, R Lu

Three cell lines derived from liver carcinoma specimens of two male and one female operated patients have been successfully established in vitro and designated by the names of BEL-7402, BEL-7404 and BEL-7405. In the course of the establishment (from the 2nd transfer onwards) studies were made to characterize them. The doubling time of cell population was found to be 20--26 hr. They formed tumor nodules upon heterologous transplantation. They appeared as epithelial-like cells in morphology and showed, in addition to desmosomes, the presence of cytoplasmic tonofibrills which were typical of epithelial cells by electron microscopy. The ultrastructural features were different from normal human liver cells, but similar to clinical hepatoma cells. They had hypotriploid chromosone number with one abnormally long acrocentric chromosome present in all 3 cell lines and additional small acrocentric chromosome and chromosome fragment in BEL-7405 line of cells. AFP were detected intracellularly by the indirect immunofluorescent method. LDH isoenzyme showed a pattern different from that of human adult liver, but similar to those of embryonic liver and clinical hepatoma with the increase of the percentage of LDH-1 (H-type) at the expanse of LDH-5 (M-type), i.e. with a higher H/M ratio. The results suggest the 3 lines of liver carcinoma cells as rapidly growing and not well differentiated epithelial-like malignant cells.

从两名男性和一名女性手术患者的肝癌标本中成功建立了三个细胞系,并命名为BEL-7402, BEL-7404和BEL-7405。在建立过程中(从第二次转移开始)进行了研究,以确定其特征。细胞群倍增时间为20 ~ 26小时。异体移植后形成肿瘤结节。在形态学上表现为上皮样细胞,电镜下除桥粒外,还可见典型上皮细胞的细胞质张力原纤维。超微结构特征与正常人肝细胞不同,但与临床肝癌细胞相似。它们的染色体数目为低三倍体,在3个细胞系中都有一条异常长的顶心染色体,在BEL-7405细胞系中有小的顶心染色体和染色体片段。采用间接免疫荧光法检测细胞内AFP。LDH同工酶表现出与人成人肝脏不同的模式,但与胚胎肝脏和临床肝癌相似,随着LDH-5 (M型)的扩大,LDH-1 (H型)的百分比增加,即H/M比值更高。结果表明,3株肝癌细胞均为生长迅速、分化不佳的上皮样恶性细胞。
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引用次数: 0
Mapping and characterization of the hisD-unlinked nif mutants in Klebsiella pneumoniae. 肺炎克雷伯菌hisd非连锁nif突变体的定位和表征。
Pub Date : 1980-02-01
Z Xue, Q Jiang, S Shen

Two hisD-unlinked genes NifC5 and NifC7 are mapped in the chromosome of K. pneumoniae. The sequence of NifC5 and NifC7 is suggested as NifC5--gltB--NifC7--argG. The P1 infected E. coli lysate can transduce the mutant C-7 to be Nif+ transductant, yet fails to transduce the hisD-linked nif mutants to be Nif+ ones. This indicates that the gene encoding C-7 is not the structural gene of nitrogen fixation and is present in E. coli. It is actually a gene specifying the glutamate synthetase. SDS electrophoresis shows the marked low content of nitrogen reductase and immunoelectrophoretic test reveals the reduced amount of both nitrogenase and nitrogen reductase in the mutant cells.

两个非hisd连锁基因NifC5和NifC7在肺炎克雷伯菌的染色体上被定位。NifC5和NifC7的序列建议为NifC5—gltB—NifC7—argG。P1感染的大肠杆菌裂解液可以将突变体C-7转导为Nif+转导剂,但不能将hisd连接的Nif突变体转导为Nif+。这表明编码C-7的基因不是固氮结构基因,存在于大肠杆菌中。它实际上是一个指定谷氨酸合成酶的基因。SDS电泳显示突变体细胞中氮还原酶含量明显降低,免疫电泳检测显示突变体细胞中氮还原酶和氮还原酶含量均降低。
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引用次数: 0
Complementation analysis and characterization of the nitrogen fixation genes, nifH, nifC and nifJ in Klebsiella pneumoniae. 肺炎克雷伯菌固氮基因nifH、nifC和nifJ的互补分析与特性
Pub Date : 1980-01-01
J Runzhi, H Yide, S Meijing, C J Biao, G Dean, S Bingfu, L Wujun, S Shanjiong

Complementation tests were performed with various nif mutations for delineating the nif genes. The nif-/nif- heterogenotes were constructed by transferring nif plasmid mutant PRD-nif- from E. coli Jc5466 to various Klebsiella pneumoniae nif- recipients. In addition to those nif genes previously reported elsewhere, a new essential gene for nitrogen fixation, nifC was identified. According to the P1-transduction and three factor reciprocal crosses, nifC was tentatively mapped between nifH and nifJ in the chromsome. The order of nif genes obtained was hisD, nifQ, nifB, nifA, nifL, nifF nifM, nifV, nifS, nifU, nifN, nifE, nifK, nifD, nifH, nifC and nifJ. The examination of the biochemical phenotypes of the nif genes suggests that nifC may be concerned with the synthesis or activation of the iron molybdenum cofactor nitrogenase, nifH, besides coding for the structure of nitrogen reductase may also exert a function on the synthesis of nitrogenase, and nifJ presumably is required to turn on the expression of nifK (D), nifH or nifF.

用不同的nif突变进行互补试验,以描绘nif基因。通过将nif质粒突变体PRD-nif-从大肠杆菌Jc5466转移到不同的肺炎克雷伯菌nif-受体,构建了nif-/nif-异种。除了先前在其他地方报道的nif基因外,还发现了一个新的固氮必需基因nifC。根据p1转导和三因子正交,nifC初步定位在染色体上的nifH和nifJ之间。获得的nif基因顺序为hisD、nifQ、nifB、nifA、nifL、nifF、nifM、nifV、nifS、nifU、nifN、nifE、nifK、nifD、nifH、nifC和nifJ。对nif基因的生化表型检测表明,nifC可能与铁钼辅助因子氮酶nifH的合成或激活有关,除了编码氮还原酶的结构外,nifJ也可能对氮酶的合成起作用,nifJ可能是开启nifK (D)、nifH或nifF表达所必需的。
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引用次数: 0
Effect of n-butanol on Na+, K+-ATPase. 正丁醇对Na+, K+- atp酶的影响。
Pub Date : 1980-01-01
L Qishui, L Yun

The effect of n-butanol on the activity of Na+, K+-ATPase has been found different at different temperatures. Below the phase-transition temperature, n-butanol has a stimulating effect provided the concentration is not higher than 0.3 M. But if the activity is determined above the phase-transition temperature, n-butanol has an inhibitory effect. The p-nitrophenyl phosphatase activity has been found to be inhibited by n-butanol even at comparatively low temperatures. This is in accord with the finding that the Arrhenius plot for p-nitrophenyl phosphatase did not show any break. It is suggested that at lower temperatures the conformational change involved in the transport of Na+, K+ ions may be the rate-limiting factor in the overall reaction, and n-butanol may be used as a probe for perturbation of the membrane to elucidate the mechanism of Na+, K+-ATPase.

正丁醇对Na+, K+- atp酶活性的影响在不同温度下存在差异。在相变温度以下,浓度不高于0.3 m时,正丁醇具有刺激作用,但在高于相变温度时,正丁醇具有抑制作用。对硝基苯磷酸酶活性被正丁醇抑制,即使在较低的温度下。这与对硝基苯磷酸酶的阿伦尼乌斯图没有出现断裂的结果一致。结果表明,在较低温度下,Na+, K+离子运输过程中的构象变化可能是整个反应的限速因素,正丁醇可以作为扰动膜的探针来阐明Na+, K+- atp酶的机制。
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引用次数: 0
Comparison of physiological responses to hypoxia at high altitudes between highlanders and lowlanders. 高原人和低地人在高海拔地区对缺氧的生理反应比较。
Pub Date : 1979-12-01
S Zhongyuan, N Xuehan, H Pengguo, Z Shoucheng, Z Deming, Y Shengyue, W Yan, D Zhaoshen

This report deals with the differences and changes of physiological functions of the highlanders and the lowlanders at different altitudes during the period when the Chinese Mountaineering Team was climbing up and reached the peak of Qomolangma Feng. In a period of relaxation, there are no significant changes in ventilatory responsiveness to hypercapnia, electrocardiogram and electroencephalogram between highlanders and lowlanders with the changes at different altitudes. At 5,000 m a.s.l., however, electrocardiogram and the result of cardiac ventricular functional test show significant differences after the subjects are physically loaded. Those whose electrocardiogram readings show unusual changes, and whose cardiac ventricular functional tests show their physiological functions at low degree after physical activities at the altitude of 5,000 m, have a climbing ability hardly below 6,500 m, while those who have reached the altitudes above 8,200 m have no unusual changes in electrocardiogram, and the results of cardiac ventricular functional tests show that their physiological functions are at high degree.

本文报道了中国登山队在攀登珠峰峰顶的过程中,高原人和低地人在不同海拔高度的生理机能的差异和变化。在放松期,高原人和低地人对高碳酸血症的通气反应性、心电图和脑电图没有明显变化,只是海拔不同。然而,在5000 m a.s.l.时,受试者在体力负荷后的心电图和心室功能检查结果有显著差异。在海拔5000米体力活动后,心电图读数异常变化,心室功能检查显示生理功能程度较低的人,其攀登能力几乎不低于6500米,而到达海拔8200米以上的人,其心电图无异常变化,心室功能检查结果显示其生理功能程度较高。
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引用次数: 0
Partial synthesis of harringtonine. 三尖杉碱的部分合成。
Pub Date : 1979-11-01
Huang Liang, Xi YuGui, Guo JiYu, Liu DaKuan, Xu ShiPing, Wu KeMei, Cheng JiaChong, Jiang YunZhen, Gao YouSong, Guo ZongRu, Li LanMin, Zhang ManYun, Chu FengMing

The partial synthesis of harringtonine from cephaltotaxine has been described. A key intermediate, 5, 5-dimethyl-2-hydroxytetrahydrofuran-2-carboxylic acid (V), prepared from 4-methyl-1, 4-valerolactone, was dehydrated smoothly to give 5, 5-dihydrofuran-2-carboxylic acid (VI), Through its sodium salt, VI was converted into the corresponding acyl chloride VIII, which reacted with cephalotaxine in the presence of pyridine to give ester IX. After being treated with hydrichloric-acetic acid, ester IX unerwent Reformatsky reaction to give a mixture (XIV) of harringtonine and its diastereoisomer (epiharringtonine) as the final product which was purified either by countercurrent distribution or column chromatography on neutral alumina. The amounts of the two epimers in the mixture shown by TLC were roughly equal.

本文报道了由头紫杉醇部分合成三尖杉碱的方法。由4-甲基- 1,4 -戊内酯制备的关键中间体5,5 -二甲基-2-羟基四氢呋喃-2-羧酸(V)顺利脱水得到5,5 -二氢呋喃-2-羧酸(VI), VI通过其钠盐转化为相应的酰氯VIII,与头孢噻嗪在吡啶存在下反应生成酯IX。经盐酸乙酸处理后,酯IX进行Reformatsky反应得到三尖杉碱及其非对映异构体(表三尖杉碱)的混合物(XIV),最终产物在中性氧化铝上采用逆流分布或柱层析提纯。TLC显示混合物中两种引物的含量大致相等。
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引用次数: 0
Studies on a new antiarrhythmic drug changrolin-4-(3',5'-bis [(N-pyrrolidinyl) methyl]-4'-hydroxyanilino)-quinazoline. 抗心律失常新药长咯林-4-(3′,5′-双[(n-吡咯烷基)甲基]-4′-羟基苯胺)-喹唑啉的研究。
Pub Date : 1979-10-01
L Q Li, Z X Qu, Z M Wang, Y L Zeng, G S Ding, G J Hu, X Y Yang

Changrolin is 4-(3', 5'-bis[(N-pyrrolidinyl)methyl]-4'-hydroxyanilino)-quinazoline. It is a novel type of antidysrhythmic drug. It has been synthesized in 4 steps. According to our experiments, changrolin exhibited significant protective and therapeutic effects against experimental arrhythmias induced by aconitine or ouabain. It raised the electrical threshold of ventricular fibrillation. Intravenous injections in dogs and rabbits caused (i) a mild tachycardia followed by bradycardia; (ii) a prolongation of P-R interval and a widening of QRS complex in the electrocardiogram; (iii) a gradual hypotehsion; (iv) a slight weakening of cardiac functions; and (v) only moderate influences on the hearts of dogs and rabbits when the rate of infusion was less than 1 mg/min. Changrolin could be well absorbed by oral administration. Absorption appeared to be more rapid and complete by intramuscular injection. 14C-labelled changrolin was distributed mainly in the liver and the alimentary tract.

长罗林是4-(3′,5′-双[(n -吡咯烷基)甲基]-4′-羟基苯胺)-喹唑啉。它是一种新型的抗心律失常药物。它是通过4步合成的。根据我们的实验,长络林对乌头碱或乌阿巴因引起的实验性心律失常具有显著的保护和治疗作用。它提高了心室颤动的电阈值。在狗和兔子中静脉注射引起:(1)轻度心动过速,然后是心动过缓;(ii)心电图P-R间期延长,QRS复合体增宽;(iii)渐进假设;(四)心功能轻微减弱;(v)当给药速率小于1 mg/min时,对犬、兔心脏的影响仅为中度。长rolin口服吸收良好。肌内注射吸收似乎更迅速和完全。14c标记的长rolin主要分布在肝脏和消化道。
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引用次数: 0
Microscopic and submicroscopic studies on the peripheral nerve and the skeletal muscle of the female. cadaver found in the Han Tomb No.1. 女性周围神经和骨骼肌的显微和亚显微研究。汉墓一号发现的尸体。
Pub Date : 1979-09-01
G Z Zheng, W H Feng, Y H Boa, J N Xue, Y S Ying

The present paper deals with the microscopic and submicroscopic structures of the peripheral nerve of the lumbar plexus and the skeletal muscle of the m. psoas major of the ancient female cadaver buried about 2100 years ago, which was excavated from the Han Tomb No. 1 at Mawangdui (Mawangtui) near Changsha, Hunan Province. The connective tissues in the peripheral nerve and the skeletal muscle of the ancient cadaver were found well preserved. Under the electron microscope were observed the characteristic periodic bands of the collagenous fibrils as well as some axons and degenerated myelin sheath in the lumbar plexus. And in some of the better preserved nerve fibers, their axons and myelin sheaths are readily discernible. In the m. psoas major, cross striations are clearly visible in some muscle fibers. The remains of a blood vessel with only their connective tissues left were observed in the nerve of the lumbar plexus. Bacterial spores appeared in the two tissues.

本文对湖南省长沙市马王堆1号汉墓出土的一具距今2100年的古代女性尸体的腰丛周围神经和腰肌骨骼肌的显微和亚显微结构进行了研究。发现这具古代尸体的周围神经和骨骼肌的结缔组织保存完好。电镜下观察到腰丛内胶原原纤维、部分轴突及髓鞘变性的特征性周期带。在一些保存较好的神经纤维中,它们的轴突和髓鞘很容易辨认。在腰肌大肌中,一些肌肉纤维中可以清晰地看到交叉条纹。在腰丛神经中观察到残存的血管及其结缔组织。两种组织中均出现细菌孢子。
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引用次数: 0
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Scientia Sinica
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