Characterization of the common genetic defect in humans deficient in debrisoquine metabolism

In population studies of individuals given the antihypertensive drug debrisoquine, two distinct phenotypes have been described: extensive metabolizers excrete 10-200 times more of the urinary metabolite 4-hydroxydebrisoquine than poor metabolizers. In family studies the poor-metabolizer phenotype behaves as an autosomal recessive trait with an incidence between 5% and 10% in the white population of Europe and North America, and extends to the deficient metabolism of more than 20 commonly prescribed drugs. Clinical studies have shown that such individuals are at high risk for the development of adverse side effects from these and probably many other drugs. Here we show that poor metabolizers have negligible amounts of the cytochrome P450 enzyme P450db1. We have cloned the human P450db1 complementary DNA and expressed it in mammalian cell culture. Furthermore, by directly cloning and sequencing cDNAs from several poor-metabolizer livers, we have identified three variant messenger RNAs that are products of mutant genes producing incorrectly spliced db1 pre-mRNA, providing a molecular explanation for one of man's most commonly defective genes (frequency of mutant alleles 35-43%).     

Substance P-induced fibrinolysis in the forearm of healthy humans

Physiological saline with or without substance P (50 ng/ml) was infused into the humeral artery in 6 healthy males. Indices of fibrinolytic activity (whole blood diluted lysis time, euglobulin lysis time, lysis areas in non-heated fibrin plates produced by plasma or euglobulin precipitate, plasminogen plasma levels, ₂-macroglobulin, Cl-inhibitor, and ₂-antiplasmin) were evaluated in the homolateral antecubital vein before and after 5 min of substance P or saline infusion. After substance P the fibrinolytic activity increased, as can be seen from the shortening of lysis times (p<0.01) and enlargement of the lysis areas (p<0.01). A reduction of plasminogen plasma levels (p<0.01), associated with a decrease in ₂-anitplasmin (p<0.01), was also found. Alpha₂-macroglobulin and Cl-inhibitor were instead unaltered by the peptide. The saline infusion, on the other hand, was unable to modify any of the examined indices. We concluded that exogenous substance P given intra-arterially increases fibrinolytic activity in locally-sampled venous blood through a mechanism which remains to be elucidated.     

The possible involvement of protein kinase C and phospholipase A2 inHydra tentacle regeneration

The participation of protein kinase C (PKC) in the regeneration of tentacles ofHydra vulgaris was studied. Regeneration was induced by 1,2-sn-dioctanoyl-glycerol (diC₈) and the novel diterpenoidic diacylglycerol verrucosin B (VB), a potent PKC activator extracted from marine sources. VB substantially increasedHydra average tentacle number (ATN) at concentrations 10,000 times lower than those needed for diC₈ to exert an analogous effect. When both synthetic and natural VB analogues were tested, the structure/activity relationship found inHydra tentacle regeneration was identical to that known for DAG-induced activation of PKC in vitro. VB-induced increase of ATN was strongly counteracted by the PKC inhibitors sphingosine and A3, but was not synergic with a tenfold increase of extracellular Ca²⁺ concentration or with an increase of intracellular Ca²⁺ concentration obtained either with the ionophore A23187 or with thapsigargin. This suggested the involvement of a non-Ca²⁺-dependent PKC in VB-triggeredHydra tentacle regeneration. The involvement of phospholipase A₂ (PLA₂) activation inHydra regenerative processes was studied using the novel site-specific inhibitor of the enzyme, oleyloxyethylphosphorylcholine (OOPC), which brought about a striking inhibition of ATN in the low molar range. This effect was reversed by arachidonic acid (AA), while an enhancement of ATN was also observed with an inhibitor of AA uptake from membrane phospholipids, thus suggesting that PLA₂-catalysed liberation of AA is involved inHydra tentacle regeneration. OOPC also blocked verrucosin B-induced PKC-mediated enhancement of ATN, thus suggesting that this effect is also mediated by PLA₂ activation. ATN was increased also by compound 48/80, a direct activator of pertussis toxin-sensitive GTP-binding proteins, and this effect was counteracted by pertussis toxin pretreatment. None of the known AA cascade inhibitors exhibited an effect on ATN comparable to that exerted by OOPC, but, surprisingly, the cycloxygenase inhibitor indomethacin strongly enhanced ATN, thus suggesting that prostanoids might effect a negative control onHydra regenerative processes. This represents the first attempt so far reported to study the implication of more than one biochemical pathway as a signalling event in the hydroid regenerative processes.     

Hemoglobin catabolism and the killing of intraerythrocyticPlasmodium falciparum by chloroquine

To evaluate how chloroquine kills malaria parasites, hemoglobin catabolism was studied at the various stages of intraerythrocytic parasite development. We found that hemoglobin catabolism is switched off whenPlasmodium falciparum parasites mature to the late trophozoite or early schizont stages and is switched on again during the ring stage. When hemoglobin catabolism is switched off, the parasites are resistant to the morphologic effects of chloroquine. Although the ring stage parasites failed to mature in the presence of chloroquine, some of them switched on hemoglobin ingestion and became stuffed with hemoglobin-filled vesicles, indicating a distal block in catabolism. In fact, we demonstrated a high-grade block in hemozoin production during a 22 h incubation of synchronized ring forms; ferriprotoporphyrin IX (FP) incorporation into the -hematin of hemozoin decreased from 900 to 50 pmol/10⁶ parasitized erythrocytes. We propose that the primary effect of chloroquine on hemoglobin catabolism is to block FP polymerization to -hematin. Secondarily, toxic FP and FP-chloroquine complexes accumulate and are available to exert their several toxicities, which include inhibition of hemoglobindegrading proteases and membrane damage. As a consequence, maturation is arrested and eventually the parasites die and lyse.     

36种家庭日用化学品抑菌效果的研究

采用点样法测定不同品牌的牙膏、洗衣粉、洗洁精、洗发露以及化妆品等36种家庭日用化学品的抑菌效果．结果表明：洗衣粉、洗洁精以及洗发露3种家庭常用洗涤剂对大肠杆菌(E．coli)、枯草杆菌(B．subtilis)和金黄色葡萄球菌(s．aureus)的抑菌作用较好；洁诺牙膏，雕牌洗洁精，潘婷、风影和海飞丝洗发露对大肠杆菌抑制作用明显，抑菌圈直径大于20mm；雕牌、海利尔、立白和白猫洗洁精，飘影、潘婷、风影和强生婴儿洗发露对枯草杆菌抑制作用明显，抑菌圈直径大于20mm；牙膏、洗洁精、洗衣粉和化妆品对金黄色葡萄球菌的抑制作用有所不同，抑菌圈直径介于5～20mm之间．     

31P-NMR技术考察CD/SF 5W/30通用内燃机油中ZDDP在行车试验中的氧化降解机理

文中应用³¹P-NMR技术考察了CD/SF 5W/30通用内燃机油中二烷基二硫代磷酸锌（ZDDP）添加剂在行车试验条件下的氧化降解机理。研究结果表明，ZDDP的氧化降解，首先是形成硫代磷酸酯以及硫代磷酸盐，其最终氧化降解产物是磷酸酯（盐）。ZDDP的氧化降解是导致内燃机油失效的重要原因。     

免维护铅酸蓄电池也应注意日常维护

介绍了免维护铅酸蓄电池的工作原理，对其使用过程中出现的故障及产生的原因进行了分析，并对免维护铅酸蓄电池日常维护中的注意事项进行了讨论。     

晋普山3#煤采场冒顶事故浅析及防治对策

分析了采场老顶来压规律及其对采场冒顶事故的影响，针对冒顶事故的发生提出有效的预防措施。     

ORACLE环境下通用报表系统的设计

在ORALCE环境下用PRO^*C／C^ 来开发通用报表系统，用临时视图、基础表、动态SQL句等技术来提高报表系统的通用性和灵活性，以使报表系统能较好地适应应用环境的变化，通过对开发工具PRO^*C／C^ 的分析，并综合运用这些技术，提出了通用报表系统的设计思想，为用户使用ORALCE数据库生成中文报表提供了一个便利途径。