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Inhibition of invasion and intraerythrocytic development of Plasmodium falciparum by kinase inhibitors. 激酶抑制剂对恶性疟原虫侵袭及红细胞发育的抑制作用。
Pub Date : 1996-06-15 DOI: 10.1007/BF01969742
A R Dluzewski, C R Garcia

We have examined the effects of seven protein kinase inhibitors (staurosporine, genistein, methyl 2,5-dihydroxycinnamate, tyrphostins B44 and B46, lavendustin A and R03) on the erythrocytic cycle of the malaria parasite, Plasmodium falciparum. One (staurosporine) strongly inhibits serine/threonine kinases, but the remainder all exhibit a strong preference for tyrosine kinases. We have been able to discriminate between effects on invasion and on intraerythrocytic development. All reagents impeded development of intraerythrocytic parasites, though at widely differing concentrations, from the sub-micromolar to the millimolar. Several inhibitors, including staurosporine, also reduced invasion. The phosphatase inhibitor, okadaic acid, had a strong inhibitory effect both on invasion and development. The regulation of malaria development by phosphorylation or dephosphorylation reactions at several points in the blood-stage cycle is implied.

我们研究了7种蛋白激酶抑制剂(staurosporine, genistein, methyl 2,5-dihydroxycinnamate, tyrphostins B44和B46, lavendustin A和R03)对疟原虫恶性疟原虫红细胞周期的影响。一种(staurosporine)强烈抑制丝氨酸/苏氨酸激酶,但其余的都表现出对酪氨酸激酶的强烈偏好。我们已经能够区分对侵袭和红细胞内发育的影响。所有的试剂都阻碍了红细胞内寄生虫的发展,尽管浓度有很大的不同,从亚微摩尔到毫摩尔。包括staurosporine在内的几种抑制剂也能减少侵袭。磷酸酶抑制剂冈田酸对侵染和发育均有较强的抑制作用。在血期周期的几个点上,通过磷酸化或去磷酸化反应对疟疾发展的调节是隐含的。
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引用次数: 47
In situ hybridization analysis of globin mRNAs in the primitive erythroid cells of the chick embryo. 鸡胚原始红细胞珠蛋白mrna的原位杂交分析。
Pub Date : 1996-06-15 DOI: 10.1007/BF01969723
L Fucci, U Galderisi, M Piscopo, R del Gaudio, G Geraci

The possibility that the minor embryonic chick hemoglobins might be present in a particular subgroup of primitive erythroid cells has been investigated by in situ hybridization. Probe to detect the mRNA for the alpha A globin chain of the minor embryonic hemoglobin was used, and the results of the hybridization were compared with those obtained using as probes the cDNAs for total globin mRNAs. All erythroid cells circulating in a 4-day-old chick embryo gave positive signals with both probes at an approximately constant ratio. This shows that all cells contain a similar assortment of hemoglobin types, excluding the possibility that a subgroup might contain the minor primitive hemoglobins exclusively. However, the cells are not homogeneous, since about 10% of them show a distinctly higher concentration of mRNA of all globin types.

小胚胎鸡血红蛋白可能存在于一个特定的原始红细胞亚群的可能性已被原位杂交研究。用探针检测小胚血红蛋白α - A珠蛋白链mRNA,并将杂交结果与用探针检测总珠蛋白mRNA的结果进行比较。在4日龄鸡胚中循环的所有红系细胞在两种探针的作用下均以近似恒定的比例呈现阳性信号。这表明所有细胞都含有相似的血红蛋白类型,排除了一个亚群可能只含有次要的原始血红蛋白的可能性。然而,这些细胞并不是均匀的,因为大约10%的细胞显示出明显更高浓度的所有珠蛋白类型的mRNA。
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引用次数: 0
Increased melatonin levels after hemorrhagic shock in male and female C3H/HeN mice. 雄性和雌性C3H/HeN小鼠失血性休克后褪黑激素水平升高。
Pub Date : 1996-06-15 DOI: 10.1007/BF01969734
M W Wichmann, R Zellweger, C M DeMaso, A Ayala, I H Chaudry

Although hemorrhagic shock leads to significant alterations of several hormones, e.g. ACTH, corticosterone and beta-endorphin, it is not known whether plasma melatonin levels are affected under this condition and if so, whether the effects are comparable in males and females. Using a radioimmunoassay, it was found that plasma melatonin levels were significantly increased in male and proestrus female C3H/HeN mice immediately after hemorrhagic shock. However, in male mice, by two hours after hemorrhage and resuscitation, plasma melatonin returned to levels comparable to those seen in control and sham-operated animals. Proestrus female mice, on the other hand, showed significantly increased plasma melatonin levels at two hours after surgery when compared to unoperated control animals. Although the significance and biological role of the transient increased plasma melatonin levels after hemorrhagic shock remain to be determined, it appears that the pineal gland and/or an extrapineal source of melatonin, of both male and proestrus female mice responds to severe hypotension by increased release of melatonin.

尽管失血性休克会导致几种激素的显著改变,如ACTH、皮质酮和-内啡肽,但目前尚不清楚在这种情况下血浆褪黑激素水平是否受到影响,如果受到影响,这种影响在男性和女性中是否具有可变性。用放射免疫分析法发现,失血性休克后,雄性和发情期雌性C3H/HeN小鼠血浆褪黑素水平显著升高。然而,在雄性小鼠中,在出血和复苏后两小时,血浆褪黑素恢复到与对照组和假手术动物相当的水平。另一方面,与未手术的对照动物相比,发情前的雌性小鼠在手术后两小时的血浆褪黑素水平显着增加。尽管失血性休克后血浆褪黑素水平短暂升高的意义和生物学作用仍有待确定,但似乎雄性和发情前雌性小鼠的松果体和/或褪黑素的尖外来源对严重低血压的反应是通过增加褪黑素的释放。
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引用次数: 7
Tocopheryl acetates from the pupal exocrine secretion of the squash beetle, Epilachna borealis (Coccinellidae). 从北瓢虫科的南瓜甲虫蛹分泌的外分泌中提取生育酚醋酸酯。
Pub Date : 1996-06-15 DOI: 10.1007/BF01969741
A B Attygalle, S R Smedley, T Eisner, J Meinwald

The oily droplets on the pupal integumental hairs of the squash beetle Epilachna borealis contain a mixture of alpha-, beta-, gamma-, and delta-tocopheryl acetates as major constituents. In addition, the secretion contains a number of minor components that appear to be dehydrocongeners of the major components. This is the first report of the occurrence of acetate esters of any tocopherol in nature.

北斑壁虱(Epilachna borealis)蛹被毛上的油滴含有-、-、-和-生育酚乙酸酯的混合物作为主要成分。此外,分泌物中还含有一些次要成分,它们似乎是主要成分的脱氢同系物。这是自然界中首次发现生育酚的醋酸酯。
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引用次数: 5
An improved assay for UDPglucose pyrophosphorylase and other enzymes that have nucleotide products. 一种改进的udp葡萄糖焦磷酸化酶和其他具有核苷酸产物的酶的测定方法。
Pub Date : 1996-06-15 DOI: 10.1007/BF01969730
R G Duggleby, H L Peng, H Y Chang

UDPglucose pyrophosphorylase catalyses the interconversion UDPglucose plus pyrophosphate and glucose 1-phosphate plus UTP. Several assay methods for this enzyme have been described but the only one that can be used to investigate the specificity with respect to various UDPsugars is based on coupling to UTP formation. This assay employs phosphoglycerate kinase to catalyse the formation 1,3- bisphosphoglycerate which is then used to oxidise NADH in the presence of glyceraldehyde 3-phosphate dehydrogenase. We have found that the activity of phosphoglycerate kinase towards UTP is low which limits the usefulness of the assay to very low rates, in agreement with the published recommendation of Hansen et al. Here it is shown that the dynamic range of the assay is increased by more than five fold on addition of nucleoside diphosphate kinase and ADP, which convert UTP to the preferred phosphoglycerate kinase substrate, ATP. It is also shown that the improved assay is suitable for enzymes with other nucleotide triphosphate products.

UDPglucose焦磷酸化酶催化UDPglucose +焦磷酸和glucose - 1-phosphate + UTP的相互转化。已经描述了这种酶的几种检测方法,但唯一可以用于研究各种UDPsugars特异性的方法是基于与UTP形成的偶联。该试验采用磷酸甘油酸激酶催化形成1,3-二磷酸甘油酸,然后在甘油醛3-磷酸脱氢酶存在下用于氧化NADH。我们发现磷酸甘油酸激酶对UTP的活性很低,这限制了该检测的有效性,这与Hansen等人发表的建议一致。这里显示,在添加核苷二磷酸激酶和ADP后,该测定的动态范围增加了五倍以上,这将UTP转化为首选的磷酸甘油激酶底物ATP。结果表明,改进后的方法也适用于含有其他三磷酸核苷酸产物的酶。
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引用次数: 7
Dissociation constants of water-insoluble carboxylic acids by 13C-NMR. pK(a)s of mesobiliverdin-XIII alpha and mesobilirubin-XIII alpha. 水不溶性羧酸的13C-NMR解离常数。中胆红素- xiii α和中胆红素- xiii α的pK(a)s。
Pub Date : 1996-06-15 DOI: 10.1007/BF01969747
D A Lightner, D L Holmes, A F McDonagh

High-field 13C-NMR of 13C-enriched compounds in dilute aqueous d6-Me2-SO solutions provides a simple, accurate method for measuring pK(a)s of sparingly soluble carboxylic acids. Using this method, we found the pK(a)s of mesobilirubin-XIII alpha to be 4.2 and 4.9, much lower values than reported recently for bilirubin, and of mesobiliverdin-XIII alpha to be 3.9 and 5.3.

在稀水d6-Me2-SO溶液中富集13c的化合物的高场13C-NMR为测定难溶羧酸的pK(a)s提供了一种简单、准确的方法。利用这种方法,我们发现中胆红素- xiii α的pK(a)s为4.2和4.9,远低于最近报道的胆红素,中胆红素- xiii α的pK(a)s为3.9和5.3。
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引用次数: 3
Inhibition of lipid peroxidation by diterpenoid from Podocarpus nagi. 龙柏二萜对脂质过氧化的抑制作用。
Pub Date : 1996-06-15 DOI: 10.1007/BF01969731
H Haraguchi, H Ishikawa, S Sakai, B P Ying, I Kubo

A diterpenoid, totarol (1), from Podocarpus nagi was evaluated as an antioxidant. This diterpenoid inhibited autoxidation of linoleic acid. Mitochondrial and microsomal lipid peroxidation induced by Fe(III)-ADP/NADH or Fe(III)-ADP/NADPH were also inhibited. Nagilactone E (2), a norditerpene lactone isolated from the same source, had no antioxidative activity. Furthermore, totarol protected red cells against oxidative hemolysis. This diterpene was shown to be effective in protecting biological systems against oxidative stresses.

一种二萜类化合物——龙桃醇(1)被评价为抗氧化剂。这种二萜抑制亚油酸的自氧化。Fe(III)-ADP/NADH或Fe(III)-ADP/NADPH诱导的线粒体和微粒体脂质过氧化也被抑制。Nagilactone E(2),一种从同一来源分离的去二萜内酯,没有抗氧化活性。此外,紫杉醇还能保护红细胞免受氧化性溶血。这种二萜被证明在保护生物系统免受氧化应激方面是有效的。
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引用次数: 3
Altered axon terminals containing concentric lamellar bodies of cerebellar Purkinje cells in Mongolian gerbil. 蒙古沙鼠小脑浦肯野细胞轴突末端含有同心板层体的改变。
Pub Date : 1996-06-15 DOI: 10.1007/BF01969722
I K Takeuchi, Y K Takeuchi, Y Murashima, A Seto-Ohshima

Altered axon terminals containing concentric lamellar bodies were observed in cerebellar and vestibular nuclei of the Mongolian gerbil. The terminals increased in number from 30 days of age onward, and reached about tenfold at 360 days. The numbers were the same in two gerbil strains with different susceptibility to spontaneous motor seizures by various stimuli, but about threefold those in Slc:Wistar rat.

在蒙古沙鼠小脑和前庭核中观察到轴突末端含有同心板层体的改变。从30日龄开始,终端数量增加,到360日龄时达到10倍左右。在对各种刺激的自发性运动癫痫易感性不同的两种沙鼠中,这一数字相同,但约为Slc:Wistar大鼠的三倍。
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引用次数: 0
Inhibition of aldose reductase by dihydroflavonols in Engelhardtia chrysolepis and effects on other enzymes. 二氢黄酮醇对黄颡鱼醛糖还原酶的抑制及其对其他酶的影响。
Pub Date : 1996-06-15 DOI: 10.1007/BF01969729
H Haraguchi, I Ohmi, H Masuda, Y Tamura, K Mizutani, O Tanaka, W H Chou

Astilbin and neoastilbin, dihydroflavonol rhamnosides from Engelhardtia chrysolepis, showed potent inhibition of lens aldose reductase. Kinetic analysis showed astilbin exhibited uncompetitive inhibition against both dl-glyceraldehyde and NADPH. These taxifolin glycosides were selective inhibitors of aldose reductase with no inhibition of NADH oxidase.

黄芪二氢黄酮醇鼠李糖苷中降糖素和新降糖素对晶状体醛糖还原酶有较强的抑制作用。动力学分析表明,对dl-甘油醛和NADPH均表现出非竞争性抑制作用。这些杉木苷是醛糖还原酶的选择性抑制剂,对NADH氧化酶无抑制作用。
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引用次数: 20
Effect of cold exposure on electrophysiological properties of rat heart. 低温暴露对大鼠心脏电生理特性的影响。
Pub Date : 1996-06-15 DOI: 10.1007/BF01969732
P de Martino Rosaroll, P Venditti, S Di Meo, T De Leo

Male rats exposed to the cold (4 degrees C) for five or ten days exhibited modifications in their thyroid state, as documented by increases in serum thyroid hormone levels, to which differently graded modifications of heart weight/body weight ratio, heart rate, and resting metabolic rate were associated. The values of the above mentioned thyroid state indicators returned to those of the control when the animals, kept at cold for ten days, were re-exposed to room temperature (24 degrees C) for an additional 10 days. The configuration of action potentials, recorded in vitro at 26 degrees C from fibres of anterior papillary muscles, was different in control rats of different age and was affected by prolonged cold exposure. In fact, the action potential duration (APD) increased after ten days of cold exposure. In the re-exposed group the APD was not different from that of the controls. Such a pattern was not significantly modified when the stimulation frequency increased from 1 Hz to 5 Hz. The above results suggest that in cold exposure, as in experimental hyperthyroidism, thyroid hormone might exert a cardiac chronotropic effect by modifying heart electrophysiological properties. Thus thyroid hormone should play a basic role during the exposure to cold environment, stimulating the body metabolism and increasing heart rate as a response to the requirement for greater tissue perfusion.

雄性大鼠暴露在寒冷(4摄氏度)下5天或10天,甲状腺状态发生变化,血清甲状腺激素水平升高,心重/体重比、心率和静息代谢率的不同程度变化与此相关。在低温条件下保存10天后,上述甲状腺状态指标恢复到对照组水平,再在室温(24℃)下再暴露10天。在26℃条件下,不同年龄的对照组大鼠前乳头肌纤维的动作电位结构不同,且受长时间低温暴露的影响。事实上,动作电位持续时间(APD)在冷暴露10天后有所增加。再暴露组APD与对照组无明显差异。当刺激频率从1 Hz增加到5 Hz时,这种模式没有明显改变。上述结果提示,在冷暴露中,如实验性甲状腺机能亢进,甲状腺激素可能通过改变心脏电生理特性发挥心脏变时作用。因此,在寒冷环境下,甲状腺激素应发挥基础作用,刺激机体代谢,增加心率,以响应组织灌注增加的要求。
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引用次数: 7
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