运用多普勒超声心动图技术对染色体三体异常小鼠胚胎心脏发育的研究

对２０个１６三体染色体异常小鼠胚胎进行了多普勒超声心动图研究。胎龄从１０天至１５天。９例发现流入道返流波型，６例发现流出道返流波型。１２０例染色体正常胚胎无一例发现返流波型。１６三体小鼠模型作为先天性心脏病研究的理想模型，本文首次提供了对此类模型胚胎血液动力学研究的非创伤性监测方法。     

Decreased antibody-dependent cellular cytotoxicity in minimal change nephrotic syndrome

Secondary IgG response to a tetanus toxoid booster and in vitro measurement of immunoglobulin synthesis, antibody-dependent cellular cytotoxicity (ADCC) and rc="/content/r57q863578668741/xxlarge947.gif" alt="gamma" align="MIDDLE" BORDER="0">-interferon (IFN-rc="/content/r57q863578668741/xxlarge947.gif" alt="gamma" align="MIDDLE" BORDER="0">) production were evaluated in 20 healthy controls and in 17 children with minimal change nephrotic syndrome (MCNS), during the acute nephrotic phase and 6 months after remission. Defective responses were observed in all but IFN-rc="/content/r57q863578668741/xxlarge947.gif" alt="gamma" align="MIDDLE" BORDER="0"> production during the acute nephrotic phase; these improved with disease remission. There was a significant correlation between decreases in vitro IgG production and ADCC reaction. These data indicate that defective antibody production is associated with decreased ADCC during the acute nephrotic phase of MCNS.     

抗肿瘤药复方三生注射液的研究

复方三生注射液是由生附片等六味中药组成的静注用灭菌水溶液。本文综合报道了该制剂的制备方法,质量分析,抗肺癌作用的药理及临床等研究的主要内容。结果表明,本品是治疗中晚期肺癌有效的中药复方注射剂。     

Only activated but not non-activated presynaptic α2-autoreceptors interfere with neighbouring presynaptic receptor mechanisms

Summary Experiments were carried out in rabbit cerebrocortical slices in order to find out whether the attenuation by presynaptic rc="/content/r2318063g024x323/xxlarge945.gif" alt="agr" align="BASELINE" BORDER="0">₂-autoreceptors of effects mediated by presynaptic opioid rc="/content/r2318063g024x323/xxlarge954.gif" alt="kappa" align="BASELINE" BORDER="0">- and adenosine A₁-receptors requires activation of the rc="/content/r2318063g024x323/xxlarge945.gif" alt="agr" align="BASELINE" BORDER="0">₂-receptors. The slices were preincubated with ³H-noradrenaline and then superfused with medium containing desipramine 1 rc="/content/r2318063g024x323/xxlarge956.gif" alt="mgr" align="MIDDLE" BORDER="0">mol/l. They were stimulated electrically either with single pulses or with trains of 32 pulses at 1 Hz.The overflow of tritium elicited by a single pulse amounted to 0.21% of the tritium content of the tissue. It was Ca²⁺-dependent and tetrodotoxin-sensitive and not changed by rauwolscine 1 rc="/content/r2318063g024x323/xxlarge956.gif" alt="mgr" align="MIDDLE" BORDER="0">mol/l or yohimbine 0.3 rc="/content/r2318063g024x323/xxlarge956.gif" alt="mgr" align="MIDDLE" BORDER="0">mol/l. Ethylketocyclazocine (EK; 0.1–10 nmol/l) and R-(–)-N⁶-phenylisopropyladenosine (PIA; 1–1,000 nmol/1) potently inhibited the overflow evoked by a single pulse, and their effects were not changed by yohimbine. — The overflow of tritium elicited by trains of 32 pulses at 1 Hz amounted to 0.92% of the tritium content of the tissue and was increased approximately fourfold by yohimbine 0.3 rc="/content/r2318063g024x323/xxlarge956.gif" alt="mgr" align="MIDDLE" BORDER="0">mol/l. EK and PIA were less potent inhibitors than in the one pulse experiments. Yohimbine greatly enhanced the effects of EK and PIA. The enhancement was even more pronounced when the Ca²⁺ concentration in the medium was reduced in order to obtain a control tritium overflow similar to that evoked by 32 pulses in the absence of yohimbine.The results demonstrate that there is no rc="/content/r2318063g024x323/xxlarge945.gif" alt="agr" align="BASELINE" BORDER="0">₂-adrenergic autoinhibition when noradrenaline release is elicited by a single pulse. Under these conditions, the non-activated presynaptic rc="/content/r2318063g024x323/xxlarge945.gif" alt="agr" align="BASELINE" BORDER="0">₂-adrenoceptor does not interfere with presynaptic opioid rc="/content/r2318063g024x323/xxlarge954.gif" alt="kappa" align="BASELINE" BORDER="0">- and adenosine A₁-receptor mechanisms. It is only when the autoreceptor is activated by released noradrenaline that it attenuates neighbouring presynaptic receptor mechanisms, and this attenuation is removed by rc="/content/r2318063g024x323/xxlarge945.gif" alt="agr" align="BASELINE" BORDER="0">₂-adrenoceptor antagonists.Send offprint requests to N. Limberger at the above address     

Thiol Reduction of 3′-Azidothymidine to 3′-Aminothymidine: Kinetics and Biomedical Implications

The ability of thiols to reduce 3rc="/content/t48jt274574gh5r2/xxlarge8242.gif" alt="prime" align="BASELINE" BORDER="0">-azidothymidine (AZT) to 3rc="/content/t48jt274574gh5r2/xxlarge8242.gif" alt="prime" align="BASELINE" BORDER="0">-aminothymidine has been investigated. Incubation with glutathione, dithiothreitol (DTT), or mercaptoethanol at pH 7.2 and 37°C leads to quantitative reduction of the azido moiety to an amine. The reaction is first order in AZT and first order in reducing agent (mono- or dithiol). The second-order rate constants are 2.77 × 10^–3, 6.55 × 10^–5, and 6.35 × 10^–6 M ^–l sec^–1 for the dithiothreitol, glutathione, and mercaptoethanol reductions, respectively. The thiol reduction of alkyl azide to amine under mild conditions is a synthetic method particularly suitable for water-soluble azido compounds that are sensitive to catalytic hydrogenation. The potential for the mono- or dithiol-mediated reduction of alkyl azides under biological conditions must be considered when conducting studies of azido drugs.     

Regional brain kinetics of 6-fluoro-(β-11C)-L-dopa and (β-11C)-L-dopa following COMT inhibition. A study in vivo using positron emission tomography

Summary The regional brain kinetics of (rc="/content/r45512403483pk3m/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-11C)-L-dopa and 6-fluoro-(rc="/content/r45512403483pk3m/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-11C)-L-dopa was measured in six Rhesus monkeys using positron emission tomography (PET). Radioactivity accumulated specifically in the striatal region and the increase in L-dopa-derived radioactivity utilization with time was calculated using surrounding brain as a reference area, this being devoid of dopaminergic activity. The rate constant for selective striatal utilization i.e. grossly decarboxylation was 0.0110 ± 0.0007 (S.D) and 0.0057 ± 0.0006 min1 for (rc="/content/r45512403483pk3m/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-11C)-L-dopa and 6-fluoro-(rc="/content/r45512403483pk3m/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-11C)-L-dopa, respectively. After pre-treatment of the monkeys with the peripherally and centrally active catecholamine-O-methyl transferase (COMT) inhibitor Ro 40-7592 10 mg/kg, the decarboxylation rate remained unchanged (0.0112 ± 0.0015 min-1) for (rc="/content/r45512403483pk3m/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">11C)-L-dopa, whereas an increase in rate was measured for 6-fluoro-(rc="/content/r45512403483pk3m/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-11C)L-dopa (0.0092 ± 0.0015 min–1). Differences in the distribution of radiolabelled metabolites i.e. the corresponding O-methyl-L-dopa in the reference area is most probably the reason for the difference in calculated decarboxylation rate seen between the radiotracers. The higher decarboxylation rate measured for 6-fluoro-(rc="/content/r45512403483pk3m/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-11C)-L-dopa after blockade of COMT shows that the radiolabelled metabolites i.e. 6-fluoro-O-methyl-(rc="/content/r45512403483pk3m/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-11C)-L-dopa significantly contributes to background radioactivity.     

Spectrum of morphological appearance of amyloid deposits in Alzheimer's disease

Summary Immunocytochemical staining with monoclonal antibodies to the rc="/content/w0163080366r561t/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-protein on tissue sections which have been pretreated with formic acid is not only a very specific but also a highly sensitive method for the detection of amyloid deposits in the brains of Alzheimer's disease victims. We report here a spectrum of morphological appearance of the brain amyloid deposits which are one of the main histopathological correlates of this disorder. Deposits of the rc="/content/w0163080366r561t/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-protein are not only found in the well-known lesions [congophilic angiopathy and senile (neuritic) plaques] but are also seen under various morphological forms for which the word rc="/content/w0163080366r561t/xxlarge8220.gif" alt="ldquo" align="MIDDLE" BORDER="0">plaquesrc="/content/w0163080366r561t/xxlarge8221.gif" alt="rdquo" align="MIDDLE" BORDER="0"> does not appear an appropriate term: amyloid fibrils are found as large areas of diffuse infiltration of the neuropil, as ribbon-like infiltration in the subpial layer of the cerebral cortex, as granular deposits in the white matter, as diffuse deposits in the molecular layer of the cerebellum and the basal ganglia and as star-shaped deposits in the cerebellar Purkinje cell layer. The morphology of these deposits seems to depend on the cyto-and fibroarchitectonics of the brain region in which they are found, on the amount of amyloid deposited, and also on the type of staining technique used. It is only under specific circumstances that the deposition of amyloid in the neuropil is accompanied by the formation of paired helical filaments in nerve cell processes and their parent perikarya. In conclusion, our studies suggest that the extent of brain amyloidosis in Alzheimer's disease is much wider than so far appreciated.Supported in part by grants 5-AGO-4220-05 and 5-HD-22634-02 from the National Institutes of Heath     

Preponderance of β- over α-adrenoceptors in mediating the positive inotropic effect of phenylephrine in the ferret ventricular myocardium

Summary [³H]prazosin bound to the membrane fraction derived from the ferret ventricular muscle with high affinity in a saturable manner (K _d = 0.25 nmol/l and B _max = 27 fmol/mg protein in the right ventricle). [³H]CGP-12177, a rc="/content/q36337836672084r/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-adrenoceptor ligand, bound to the membrane fraction with a _{K d} value of 0.29 nmol/l and a B _max of 42 fmol/mg protein. In the isolated ferret papillary muscle driven at 1 Hz at 37°C, phenylephrine elicited a concentration-dependent positive intropic effect. The maximal effect of phenylephrine was comparable to that of isoprenaline. Prazosin (0.3 rc="/content/q36337836672084r/xxlarge956.gif" alt="mgr" align="MIDDLE" BORDER="0">ol/l) shifted the concentration-response curve for phenylephrine slightly but significantly to the right, the maximal response being unaffected. In contrast, bupranolol (0.3 gmol/l) shifted the curve for phenylephrine markedly downwards: the maximal response was depressed significantly to 40% and the curve became less steep. In the presence of prazosin and bupranolol the curve was shifted to the right, being essentially parallel to the control curve. These results indicate that in the ferret ventricular myocardium both rc="/content/q36337836672084r/xxlarge945.gif" alt="agr" align="BASELINE" BORDER="0">- and rc="/content/q36337836672084r/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-adrenoceptors mediate the positive inotropic effect of phenylephrine. The extent of contribution of the two classes of adrenoceptor is quite different from that in other mammalian species. In the ferret heart, rc="/content/q36337836672084r/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-adrenoceptors predominate over rc="/content/q36337836672084r/xxlarge945.gif" alt="agr" align="BASELINE" BORDER="0">-adrenoceptors in mediating the positive inotropic effect of phenylephrine, although the number of rc="/content/q36337836672084r/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-adrenoceptors is not especially high when compared with other species. Send offprint requests to M. Endoh at the above address     

The effects of clonidine and yohimbine on human information processing

The effects of clonidine and yohimbine on human information processing were tested in six normal volunteers ages 18–30 years. Subjects were tested in a pre-post design with sessions conducted at weekly intervals. Three drug conditions were: Placebo (lactose), 0.2 mg clonidine, and 30 mg yohimbine. Two choice reaction time (RT) tasks were used. One was a stimulus evaluation-response selection task (SERS) that has been shown to be sensitive tod-amphetamine, methylphenidate and scopolamine. The other task was to assess stimulus pre-processing and used spatial frequency as a discriminative stimulus. The principle finding was that clonidine slowed RT; this effect was significant for both tasks. In contrast, yohimbine tended to speed RT, but the effects were significant only for the spatial frequency task on some analyses while not for others. RTs to high spatial frequency stimuli were speeded more than for low spatial frequency. The effects of these two NE drugs were compared with findings withd-amphetamine and scopolamine and interpreted within the framework of a serial information processing model proposed by Callaway (1983). Specifically, it is suggested that yohimbine and clonidine affect an early pre-processing stage.     

Effect of amino acid derivatives of β-carboline-3-carboxylate on behavior in rats

Brain Research Institute, All-Union Mental Health Research Center, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR O. S. Adrianov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 107, No. 5, pp. 586–587, May, 1989.