Structure-activity relationships of (+)-CC-1065 analogues in the inhibition of helicase-catalyzed unwinding of duplex DNA.

(+)-CC-1065 is a potent antitumor antibiotic produced by Streptomyces zelensis. Previous studies have shown that the potent cytotoxic and antitumor activities of (+)-CC-1065 are due to the ability of this compound to covalently modify DNA. (+)-CC-1065 reacts with duplex DNA to form a (N3-adenine)-DNA adduct which lies in the minor groove of DNA overlapping with a five base-pair region. As a consequence of covalent modification with (+)-CC-1065, the helix bends into the minor groove and also undergoes winding and stiffening. In the studies described here, we have constructed templates for helicase-catalyzed unwinding of DNA that contain site-directed (+)-CC-1065 and analogue DNA adducts. Using these templates we have shown that (+)-CC-1065 and select synthetic analogues, which have different levels of cytotoxicity, all produce a significant inhibition of unwinding of a 3'-tailed oligomer duplex by helicase II when the displaced strand is covalently modified. However, the extent of helicase II inhibition is much more significant for (+)-CC-1065 and an analogue which also produced DNA winding when the winding effects are transmitted in the opposite direction to the helicase unwinding activity. This observed pattern of inhibition of helicase-catalyzed unwinding of drug-modified templates was the same for a 3'-T-tail, for different duplex region sequences, and with the Escherichia coli rep protein. Unexpectedly, the gel mobility of the displaced drug-modified single strand was dependent on the species of drug attached to the DNA. Last, strand displacement by helicase II coupled to primer extension by E. coli DNA polymerase I showed the same pattern of inhibition when the lagging strand was covalently modified. In addition, the presence of helicase II on single-stranded regions of templates caused the premature termination of primer extension by DNA polymerase. These results are discussed from the perspective that (+)-CC-1065 and its analogues have different effects on DNA structure, and these resulting structural changes in DNA molecules are related to the different in vivo biological consequences caused by these drug molecules.     

中药黄精中的新生物碱

中药黄精中的新生物碱孙隆儒１）王素贤李铣（沈阳药科大学天然药物研究室，沈阳１１００１５）黄精为百合科黄精属植物黄精（ＰｏｌｙｇｏｎａｔｕｍｓｉｂｉｒｉｃｕｍＲｅｄｏｕｔｅ）的根茎，具有补气养阴、ＦｉｇＳｔｒｕｃｔｕｒｅｏｆｔｈｅｃｏｍｐｏｕｎｄ健脾、...     

创收工资—医院按劳分配的探索

遵循“各尽所能，按劳分配”的社会主义分配原则，我院对职工分配进行了积极的探索。从８０年代初起，在院内实行定量、定质的超额劳务提成。但随着医院改革不断深化，医院总收入增加，院内、外独立核算，限期还本息项目增多，原超额劳务提成办法不能适应医院发展。因此，在原有基本工资、奖励工资基础上，增设了创收工资，医院对创收工资从质量、数量、文明建设、医德医风建设等方面进行宏观调控。创收工资使科主任责、权、利落到实     

白细胞介素—2新的功能位点及其中枢镇痛作用

白细胞介素－２（ＩＬ－２）不仅是重要的免疫调节因子，而且还具有重要的中枢调节作用。本实验以钾离子透入引起大鼠甩尾反应为指标，发现侧脑室注射ＩＬ—２能显著提高动物痛阈，并能被纳洛酮所阻断，表示ＩＬ－２的中枢镇痛作用可能与阿片受体有关。利用基因定位突变技术获得的无免疫活性ＩＬ－２实查体仍具有中枢镇痛作用，表明ＩＬ—２分子上发挥镇痛和免疫调节作用的功能位点是相互独立的。纳洛酮能够阻断ＩＬ—２的中枢镇痛作用，而不能影响ＩＬ—２增殖ＣＴＬＬ－２细胞的作用，提示ＩＬ－２发挥镇痛和免疫调节作用可能通过不同的受体途径。ＩＬ－２分子中第４５位Ｔｙｒ残基突变为Ｖａｌ后，虽仍保留了免疫活性，但丧失了镇痛功能，表示４５位Ｔｙｒ残基是ＩＬ—２发挥中枢镇痛功能的关键残基之一。我们推测ＩＬ—２的镇痛功能位点可能在ＩＬ—２分子中第４５位Ｔｙｒ残基附近区域。     

A comparative study of pepsinogen (PG) and lactic acid dehydrogenase (LDH) activities and isoenzyme patterns in tissues from human primary gastric cancer, gastric cancer xenografts in nude mice and gastric cancer cell lines]

Tissue and cell homogenates were prepared for PG and LDH study from 20 samples of histologically proven gastric cancer (GC), 6 samples of gastric cancer xenografts (THPGC-1) of different passages (GCXG) and cultured cells of 3 different gastric cancer cell lines (GCCL). Normal gastric mucosa (NGM) was also obtained from the resected stomach far distant from the primary tumor and histologically tumor free. The results indicated that the expression of PG isoenzymes was low or absent and the PG activities were significantly decreased in GC, GCXG and GCCL as compared to NGM. The activity of LDH was also significantly increased in GC, GCXG and GCCL. In addition, there was a change in isoenzyme pattern in GC and GCXG in which isoenzyme type M was observed whereas isoenzyme type H was preponderent in NGM. The results show that the human gastric cancer xenograft, THPGC-1, has biological properties very similar to those of the primary tumor suggesting that THPGC-1 is a reliable model for the study of the molecular biology of human gastric cancer.     

润滑油抗泡机理的研究 Ⅱ.助泡剂对泡沫倾向的影响及抗泡剂配伍性能

考察了各类添加剂在不同浓度、温度及不同基础油中的泡沫倾向,并测定了这些条件下体系的表面张力。从表面化学角度解释了添加剂对泡沫性质的影响,并通过对抗泡剂配伍性能的研究,验证了消泡机制:抗泡剂须具备高的表面活性才能吸附于泡膜表面,降低泡膜的表面粘弹性,改变膜的流变性能,从而起消泡作用。     

Good regulation of acupuncture in simple obesity patients with stomach-intestine excessive heat type

In order to investigate the regulatory effect of acupuncture on obesity patients with the Stomach-Intestine Excessive Heat Type, the pre-acupunctureal and post-acupunctural obesity index and biochemical indices of 718 simple obesity patients with Stomach-Intestine Excessive Heat Type were observed. It was showed that the marked weight loss effect was achieved in the cases by acupuncture, and the biochemical indices improved. It suggests that acupuncture had a optimal regulatory effect on the function of nerve, endocrine, digestion and energy metabolism.     

Medullospinal vasomotor neurones mediate hypotension from stimulation of prefrontal cortex.

Electrical stimulation of the prefrontal cortex in anaesthetised, paralysed rats evokes transient hypotension. In this study we have endeavoured to determine whether this evoked response is mediated by the spinal cord-projecting vasomotor neurones of the rostroventrolateral medulla (RVL). The responses of RVL-spinal vasomotor neurones to electrical stimulation of the prefrontal cortex caused a period of inhibition of the neuronal activity in the majority of cases (11 out of 13 neurones tested, 85%) and a short period of excitation in the remaining 2 neurones (15%). The prefrontal cortex-evoked inhibition of RVL-spinal vasomotor neurones was eliminated by iontophoretic application of bicuculline, a GABAa receptor antagonist, to the RVL-spinal vasomotor neurones. Microinjection of 50 nl of bicuculline methiodide into the same area of the RVL where the neurones have been identified converted the prefrontal-evoked hypotension into a vasopressor response. These findings indicate that the hypotension evoked by stimulating the prefrontal cortex is mediated by GABAergic inhibition of the RVL-spinal vasomotor neurones.     

An electrophysiological correlate of protein kinase C isozyme distribution in cultured cerebellar neurons.

Protein kinase C (PKC) is a family of at least seven closely related molecules (isozymes) that vary in terms of their requirements for activation and their distribution among cells of the brain. A striking example of this differential distribution is seen in the cerebellum, where Purkinje cells express PKC-I, an isozyme that is strongly activated by both phorbol ester (PE), and low doses of cis-unsaturated fatty acid (c-UFA), while granule cells predominantly express PKC-II, an isozyme that is strongly activated by PE but not c-UFA. Both Purkinje and granule cells have large, easily recorded voltage-gated K currents. These currents are attenuated by PKC activators in several other varieties of neuron. We hypothesized that the effects of these two PKC activators would be predicted by the distribution of the relevant PKC isozyme, and that the delayed outward rectifier current, IK, would be attenuated by both PE and c-UFA in Purkinje cells, but only by PE in granule cells. This hypothesis was confirmed in perforated-patch recordings. The attenuation produced by both activators could be blocked by application of a specific PKC inhibitor, RO-31-8220, and could not be mimicked by inert forms of PE or c-UFA. To our knowledge, this study represents the first report of an electrophysiological correlate of PKC isozyme distribution.