微波氚标记法与化合物结构的关系

本文报道了应用微波氚标记了许多不同类型的化合物,这些化合物的放射比度与结构紧密相关,对于在相同条件下研究不同化合物的标记比度提供了一些参考数据。     

微波对超低温细胞复温的可行性研究和若干问题的探讨

采用微波炉中的谐振场和外辐射天线的平面波对冻存在－１９６℃的活细胞进行复温试验。结果表明：谐振场加温迅速但极不均匀，造成细胞大量死亡。平面电磁波微波泄漏大，效率低，加温时间过长，不能应用。本文阐述了微波对超低温细胞复温的可能性和现有微波仪不宜进行细胞复温的原因，并提出改进设计的建议。     

肺肿瘤细胞雌激素、孕激素和凝集素受体的组化研究

用酶联亲合组化法对46例肺肿瘤细胞进行了雌激素受体(ER)和孕激素受体(PR)检测。同时测定14例肺瘤肿患者血清雌二醇(E_2)浓度。结果表明:肺肿瘤 ER 阳性率为36.9%,PR 阳性率为13.0%。阳性率与性别、病理类型及血浆 E_2浓度无关。认为肺癌的发生发展可能与雌激素有依赖关系,提示内分泌疗法可能会成为原发肺肿瘤的一种治疗手段。另用 ABC 法对上述46例肺肿瘤中的29例进行了花生凝集素受体(PNA-R)和麦胚凝集素受体(WGA-R)的检测,PNA-R 在腺癌大都为顶浆型分布,鳞癌和透明细胞癌则多为胞膜型分布。结果提示 PNA-R 是肺癌分化过程中的一种标志,对肺癌分型、预后判断有一定协助作用。同时将29例肺肿瘤 PNA-R 与 ER 状况作对比研究,探讨了二者之间的相关性及可能的发生机制。     

New evidence for a gating action of norepinephrine in central neuronal circuits of mammalian brain

Many previous studies have examined the effects of norepinephrine (NE) on neuronal responsiveness to synaptic inputs and putative transmitter substances and have described differential depressant actions of NE on stimulus evoked versus spontaneous discharge such that the "signal to noise" ratio of threshold responses was increased. In the present studies, similar experimental strategies employing a combination of microiontophoresis, single unit recording and afferent pathway stimulation in intact anesthetized and brain tissue slice preparations have revealed noradrenergic "gating" actions whereby weak or subthreshold synaptic stimuli can evoke threshold neuronal responses in the presence of iontophoretically applied NE or following electrical stimulation of the locus coeruleus. Overall, these results suggest that potentially threshold excitatory and inhibitory synaptic inputs may normally arrive at central neurons but appear weak or absent except during behavioral conditions favoring the synaptic release of NE. As such, these findings provide evidence that signal to noise ratio may not be the only potential modulatory action expressed by NE in noradrenergic target circuits of the mammalian brain.     

Interaction of 2-halogenated dATP analogs (F, Cl, and Br) with human DNA polymerases, DNA primase, and ribonucleotide reductase

Recently, 2-halogenated deoxyadenosine analogs (F, Cl, and Br) have been shown to have antitumor activity. These analogs are phosphorylated by cells and are believed to exert their cytotoxic action at the nucleoside triphosphate level. In this work the interaction of these nucleoside triphosphate analogs with potential targets, such as DNA polymerase alpha, beta, and gamma, DNA primase, and ribonucleotide reductase was examined in detail. All of these compounds competitively inhibited the incorporation of dAMP into DNA by DNA polymerase alpha, beta, or gamma. F-dATP was able to completely substitute for dATP using DNA polymerase alpha and gamma, but not with DNA polymerase beta. Cl-dATP and Br-dATP substituted poorly for dATP using DNA polymerase alpha and beta. Extension of a 32P-labeled primer by DNA polymerase alpha, beta, or gamma on a single-stranded M13 template showed that these compounds were incorporated into the 3' end of the growing DNA chain and that elongation beyond the incorporated analogs was significantly retarded for Cl-dATP and Br-dATP using either DNA polymerase alpha or beta. DNA primase using poly(dC) as template was inhibited by these compounds at a concentration 4 to 5 times greater than that required for 2-F-araATP. The 2-halogenated dATP analogs were potent inhibitors of ADP reduction by ribonucleotide reductase. In conclusion, the cytotoxic action of 2-Cl-deoxyadenosine and 2-Br-deoxyadenosine may partially be mediated through the mechanism of "self-potentiation," by depression of the deoxynucleoside triphosphate pools due to inhibition of ribonucleotide reductase, which would facilitate their incorporation into DNA and result in the inhibition of DNA synthesis.     

KMT2C通过c-Myc/CDK4信号通路调控胃癌细胞的生长与增殖

摘要:目的 探究赖氨酸特异性甲基转移酶2C(lysine specific methyltransferase 2C,KMT2C)在胃癌发生发展中的 作用及机制。方法 通过 TCGA 数据库分析 KMT2C在胃癌与癌旁的表达差异。采用 Western blot检测 KMT2C在胃 癌与癌旁临床样本中的表达差异。通过 Kaplan-Meier Plotter数据库分析 KMT2C 对胃癌患者预后的影响。采用细胞 实验(克隆形成、EdU 及 CCK-8检测)及皮下瘤负荷模型检测 KMT2C 在体内外对胃癌细胞增殖能力的影响。结果 KMT2C在胃癌中高表达。胃癌患者中 KMT2C高表达组相对于 KMT2C低表达组预后较差。敲减 KMT2C在体内外 均有抑制胃癌 细 胞 增 殖 的 作 用。基 因 集 富 集 分 析 (GSEA)发 现 KMT2C 影 响 c-Myc信 号 通 路。敲 减 KMT2C 后, H3K4me1蛋白表达水平降低,同时,CDK4的 mRNA 与蛋白表达水平降低。KMT2C与c-Myc核内结合促进了c-Myc 与 CDK4的启动子区域的结合。结论 KMT2C通过影响c-Myc/CDK4信号通路促进胃癌细胞增殖。     

The shell region of the nucleus ovoidalis: a subdivision of the avian auditory thalamus.

The connectivity of a region surrounding the established thalamic auditory nuclei, n. ovoidalis (Ov) and n. semilunaris parovoidalis (SPO), was explored in the ring dove by using the anterograde tracers, Phaseolus vulgaris leucoagglutinin (PHAL) and biocytin, and the retrograde tracer, fluorogold. The Ov-SPO surround received a projection from a cell group along the interface of the auditory midbrain and the n. intercollicularis, as revealed with PHAL and biocytin, and was composed of neurons exhibiting a common morphology. These features and the presence of overlapping projections from different portions of the Ov-SPO surround suggest that this region comprises a functionally discrete area, which we term the Ov shell. Single unit recording within the shell established the existence of acoustically responsive units. Both PHAL and fluorogold labeling revealed a robust projection from the Ov shell to the caudomedial hypothalamus. Major telencephalic projections of the shell terminated within the ventral paleostriatal complex, "end-zones" of the field L, the caudomedial hyperstriatum ventrale, and regions immediately dorsal and lateral to the auditory neostriatum. Except for a portion of the shell bordering medial ovoidalis, PHAL injections into the shell also labeled fibers within the caudolateral neostriatum and along the lateral neostriatal rim. The connectivity of the Ov shell suggests that this region may integrate auditory pathways with brain regions associated with endocrine mediated behavior. In addition, the shell may constitute a source of converging input to several levels of central auditory pathways.