胃癌组织中核基质蛋白的变化

目的：研究胃癌组织核基质蛋白的改变。方法：应用SDS－PAGE技术及Geneools定量分析软件，对22例胃癌组织及正常组织的核心基质蛋白进行了研究，结果：胃癌组织与正常组织比较，Mr为30000，28000的核基质蛋白表达量明显减少（P＜0．05），不同分化类型及不同临床分期胃癌组织间比较，此种核基质蛋白表达量差异无统计学意义（P＞0．05），结论：胃癌组织中核基质蛋白的改变可能在肿瘤的早期已经发生，是胃癌发生的早期分子事件。     

Receptor binding of N-(methyl-11C) clozapine in the brain of rhesus monkey studied by positron emission tomography (PET)

By means of positron emission tomography the uptake and kinetics of N-(methyl-¹¹C)clozapine in different brain regions have been studied in Rhesus monkeys. ¹¹C-clozapine rapidly entered the brain and maximum radioactive uptake was seen 5–12 min after administration. Highest uptake was measured in the striatum. Other regions with an uptake higher than in the cerebellum were thalamus and mesencephalon. The radioactivity from different brain regions decreased with an elimination half-life of about 5 h and parallelled the plasma kinetics of unlabelled clozapine. The striatum/cerebellum ratio of ¹¹C-clozapine-derived radioactivity remained constant during the period studied and did not change after pretreatment with atropine. In contrast, the striatum/cerebellum ratio was somewhat lower after pretreatment with N-methylspiperone (NMSP), indicating competition for the same binding sites in the striatum. After pretreatment with increasing doses of clozapine, a dose-dependent protection of binding sites in the striatum for ¹¹C-NMSP was seen. It is concluded that clozapine is more loosely bound to dopamine receptors in the striatum than N-methylspiperone and that the kinetics of clozapine in the brain parallel that in the plasma. The binding properties of clozapine within the brain may explain some of the clinical properties of the drug.     

老年大鼠脑内肾上腺素能神经递质系统的变化

本文从下丘脑、大脑皮层、海马等脑区去甲肾上腺素(NA)的含量,其合成酶与降解酶的活性、NA受体数目等多环节的测定来分析肾上腺素能神经递质系统在老化脑中的变化。实验结果表明衰老过程下丘脑、大脑皮层内NA合成酶活性没变化,NA含量明显增高,下丘脑内α_1受体数目显著减少。上述结果提示这些脑区肾上腺素能神经的活动有可能减弱。同时,海马内单胺氧化酶B(MAO B)活性明显增加,说明海马神经元外组织有增生的可能。泰文并讨论了这些变化与老年记忆、行为与神经内分泌等脑功能衰退的关系。     

Prejunctional effects of muscarinic agonists on 3H-acetylcholine release in the rat urinary bladder strip

Summary The inhibitory effects of some muscarinic agonists on tritiated acetylcholine release evoked by field stimulation were investigated in the rat urinary bladder strip. The acetylcholine stores of the preparation were labelled with ³H-choline. Electrical field stimulation caused an outflow of tritium, reflecting the release of ³H-acetylcholine. The release of ³H-acetylcholine was decreased in a concentration-dependent manner by all the agonists tested: oxotremorine, muscarone, muscarine, carbachol and methylfurtrethonium. On the contrary, only muscarine and muscarone enhanced the basal efflux of tritium in a concentration-dependent fashion. Concentration-response curves were determined both at 2 Hz and at 1 Hz by using intermittent administration of the drugs. Maximal depression in release (by 78 – 82%) was observed in experiments at 1 Hz. A similar inhibition was obtained at 2 Hz frequency only when a low concentration of calcium (0.6 mM) in the medium was used. Oxotremorine was the most potent among the tested compounds with the same intrinsic activity as the other drugs. In contrast to the other agonists investigated, oxotremorine showed in about 10-fold greater potency at pre- than at postjunctional muscarine receptors in the rat urinary bladder. This difference might depend either on heterogeneity of muscarine receptors or on different mechanism(s) relating to the transducing properties of receptors at the pre- and postjunctional level. A comparison between the relative prejunctional potencies in the rat urinary bladder and in the guinea pig myenteric plexus (data from the literature) suggests that prejunctional muscarine receptors are similar in these tissues. Furthermore, the findings obtained with a low concentration of calcium in the medium may support the view that intraneuronal availability of calcium plays a significant role in modulating the prejunctional negative feed-back mechanism in the rat urinary bladder.Send offprint requests to Dr. G. D'Agostino at the above address     

ANTIHYPERTENSIVE EFFECTS OF MESULERGINE: FURTHER EVIDENCE FOR A PERIPHERAL SITE OF ACTION OF DOPAMINE AGONISTS

The cardiovascular effects of mesulergine were studied in anesthetized dogs. Intravenous (IV) administration (0.3 mg/kg) significantly decreased blood pressure in neurogenic hypertensive dogs without any change in heart rate. This effect was completely antagonized by IV administration of domperidone (0.5 mg/kg). Intracisternal administration of mesulergine (0.03, 0.3 and 3 mg/kg) did not produce any change in blood pressure. However, with the highest dose we observed a significant rise in heart rate during the first 2 min (which was probably nonspecific). These results suggest that mesulergine lowers blood pressure in sinoaortic-denervated dogs by means of a peripheral mechanism probably involving DA2 receptors. The findings confirm the potential interest of dopamine-receptor agonists as future antihypertensive agents.     

Cerebellar nuclear afferents--where do they originate? A re-evaluation of the projections from some lower brain stem nuclei

Summary Cerebellar nuclear afferents from some caudal brain stem nuclei in the cat were studied by means of retrograde transport after implantation of the wheat germ agglutinin-horseradish peroxidase complex in crystalline form in the cerebellar nuclei. The findings give evidence that projections to the cerebellar nuclei from certain nuclei of the reticular formation proper (e.g., from the gigantocellular reticular nucleus) are very modest, while there appears to be no or extremely few cerebellar nuclear afferents from the paramedian reticular, spinal trigeminal, gracile, cuneate and external cuneate nuclei. Previous tracer studies have given evidence that also the pontine and red nuclei send very few, if any, fibres to the cerebellar nuclei. All these brain stem regions are known to project to the cerebellar cortex. This relative lack of mossy fibre collaterals to the cerebellar nuclei is discussed with references to previous literature on the distribution of cerebellar nuclear afferents, and the problem of how the cerebellar nuclei are facilitated is considered.Abbreviations Br.c. superior cerebellar peduncle (brachium conjunctivum) - Br.p. middle cerebellar peduncle (brachium pontis) - C.r. interior cerebellar peduncle (restiform body) - HRP horseradish peroxidase - L left - N.c. cuneate nucleus - N.c.e. external cuneate nucleus - N.c.t. nucleus of corpus trapezoideum - NIA anterior interposed nucleus - NIP posterior interposed nucleus - NL lateral (dentate) nucleus - N.l.l. nuclei of lateral lemniscus - NM medial (fastigial) nucleus - N.m.X. dorsal motor vagal nucleus - N.mes. mesencephalic trigeminal nucleus - N.r.l. lateral reticular nucleus (nucleus of the lateral funiculus) - N.r.p. paramedian reticular nucleus - N.r.t. reticular tegmental pontine nucleus - N V, VI, VII, XII root fibres of cranial nerves - Ol.s. superior olive - P.h. nucleus praepositus hypoglossi - Py pyramid - R right - R.gc. gigantocellular reticular nucleus - R.l. lateral reticular nucleus of Meessen and Olszewski - R.p.c. caudal pontine reticular nucleus - R.pc. parvicellular reticular nucleus - R.v. ventral reticular nucleus - Tr.sp.V. spinal tract of the trigeminal nerve - T.s. solitary tract surrounded by nucleus of solitary tract - V.m. medial vestibular nucleus - WGA wheat germ agglutinin - WGA-HRP wheat germ agglutinin-horseradish peroxidase conjugate - V, VI, VII, X, XII motor nuclei of cranial nerves     

Lithium increases slow wave sleep: possible mediation by brain 5-HT2 receptors?

The effect of lithium on slow wave sleep (SWS) was studied in ten normal male volunteers using home based cassette sleep recording and automatic sleep stage analysis. Lithium increased SWS, an effect consisten with a reduction in brain 5-HT₂ receptor function.     

Apomorphine-induced alterations in cortical EEG activity of rats

Summary EEG activity after activation of dopamine receptors of D-1 and/or D-2 type was studied by using telemetric recordings in rats. Apomorphine, a preferential D-2 agonist, produced a characteristic increase in the power of alpha-1 band (7.00–9.50 Hz) when given in doses mediating stereotypies (0.2 or 0.5 mg/kg s. c.). Low doses produced a general increase in the power of all of the bands except beta-2. In particular, delta activity was enhanced which seems to be in correspondence with the sedation observed after these doses (0.02 and 0.05 mg/kg). Haloperidol in a dose which is assumed to block both D-1 and D-2 receptors (0.1 mg/kg i. p.) completely antagonized the alpha-1 activation produced by apomorphine (0.5 mg/kg). A similar, although not complete inhibition of alpha-I activation was found after administration of a large dose of the selective D-1 antagonist SCH 23390 (0.2 mg/kg i. p.). The selective agonist at D-2 receptors quinpirole (1.0 mg/kg s. c.) produced a less pronounced activation of the power in the alpha-1 band than apomorphine.In general, there was found to be a good correlation between the activation of the alpha-1 activity and stereotyped behaviour. The results suggest that for the full expression of alpha-1 activation, a pronounced activation of D-2 receptors and at least a minimal activation of D-1 receptors, for instance by the endogenous dopamine, is necessary. Send offprint requests to K. Kuschinsky at the above address