情感障碍与D_(21)s65关联研究

目的：搜寻２１ 号染色体情感障碍易感性基因,探讨Ｄ２１ｓ６５ 多态性与情感障碍的关系。方法：应用微卫星ＤＮＡ 的二核苷酸串联重复序列多态性方法分析Ｄ２１ｓ６５ 与ＡＤ之间关系。结果：没有发现ＡＤ与Ｄ２１ｓ６５关联的证据。结论：本研究结果提示２１ｑ２２．１ 区域不存在ＡＤ易感性基因。     

舌鳞状细胞癌组织中p53、p21和bcl-2基因蛋白的表达

【目的】研究 p5 3、p2 1和bcl 2基因蛋白在舌鳞状细胞癌组织中的表达及其临床意义。【方法】用免疫组化SP法检测 5 4例舌鳞状细胞癌组织标本p5 3、p2 1和bcl 2癌基因蛋白表达。【结果】舌鳞状细胞癌组织中p5 3、p2 1和bcl 2蛋白阳性率分别为 46 %、6 1%、46 % ;p5 3和 p2 1蛋白表达与肿瘤细胞分化程度及颈淋巴结转移有关 (P <0 0 5 ) ;p5 3蛋白表达与 p2 1蛋白表达有关 (P <0 0 5 ) ,bcl 2基因蛋白表达与 p5 3或p2 1基因蛋白表达无关 (P >0 0 5 )。【结论】舌鳞状细胞癌组织中具有较高的 p5 3、p2 1和bcl 2癌基因蛋白表达 ;p5 3和 /或p2 1蛋白阳性病例恶性程度高 ,易发生颈淋巴结转移。p5 3和 /或 p2 1蛋白可作为舌鳞癌预后的参考指标     

胃癌及癌前病变组织中雌激素受体和P21ras的表达及意义

目的 探讨雌激素受体（ＥＲ）和ｒａｓ原癌基因蛋白－Ｐ２ｒａｓ的表达在胃癌发生、发展中的作用及与胃癌生物学行为的关系。方法 采用免疫组化ＳＰ法。结果 ＥＲ在慢性浅表性胃炎（２０例）、异型增生（２１例）中均为阴性,胃癌（４０例）的表达阳性率为４０％,三组比较有显著性差异（Ｉ〈０．０５）。Ｐ２１＾ｒａｓ在慢性浅表性胃炎、异型增生、胃癌的表达阳性率分别为１０％、２３．８％、４７．５％,三组比较差异有显著性     

Expression of the human multidrug resistance gene mdr1 in leukemic cells and its application in studying P-glycoprotein antagonists

Objective To explore the role of endothelin (ET) in the pathogenesis of exercise-induced asthma (EIA), we investigated the effects of ET(B) receptor antagonists, ET-1 (11-21)fragment and N-cis-2,6-dimethylpi-peridinocardonyl-L-γ-methylleucyl-D-1-methoxycarbonyl tryptophanyl-D-norleucine (BQ788) on broncho-constriction elicited by isocapnic hyperpnea in guinea pigs. Methods Eighteen pathogen-free Hartley guinea pigs were randomly divided into three groups. A: normal saline (NS) inhalation control group (n=6), B: BQ788 group (n=6), and C: ET-1(11-21) fragment group (n=6). Guinea pigs were anesthetized with pentobarbital sodium. After measuring the basal value of lung resistance (R[L]) and dynamic compliance of the respiratory system (Cdyn), NS (0.96 ml), BQ788 (9 nmol) and ET-1(11-21)fragment (9 nmol) were inhaled. A rodent respirator with a dry 5%CO(2)-95%O(2) mixture at room temperature provided mechanical ventilation (V[T] 8 ml/animal, 100 breaths/min) for 5 min. R[L] and Cdyn of the 3 groups were measured again after isocapnic hyperpnea challenge. Results In the control group, isocapnic hyperpnea of dry gas elicited a marked increase in R[L] and decrease in Cdyn. R[L] and Cdyn of the guinea pigs from BQ788 group and ET-1(11-21)fragment group did not change significantly. Conclusion It was demonstrated that selective ET(B) receptor antagonists, ET-1(11-21) fragment and BQ788, inhibited the bronchoconstriction induced by isocapnic hyperpnea in guinea pigs. The data showed that ETs are potent constrictors of guinea pig airway smooth muscle via a direct effect on ET receptors. It was suggested that ET receptor antagonists, especially ET(B) receptor antagonist, might be beneficial in preventing EIA.     

P^21和PCNA在肝硬变组织中表达的研究

目的：探讨Ｐ２１、ＰＣＮＡ的相关关系及它们在肝硬变、肝细胞不典型增生（ＬＣＤ）、肝细胞癌（ＨＣＣ）形成中的作用。方法：运用Ｓ－Ｐ法对６０例单纯肝硬变（不伴癌）、３０例癌旁肝硬变及２７便ＨＣＣ的Ｐ２１、ＨＢｓＡｇ及ＰＣＮＡ表达情况进行实验研究。结果：癌旁肝硬变组织、单纯肝硬变组织、癌组织Ｐ２１阳性率分别为９０％、６８．３３％、６２．９６％,癌旁肝硬变与单纯肝硬变,癌旁肝硬变与癌组织之间判别有显著性意     

P21CIP_1/WAF_1、CD_(44)V_6在恶性卵巢上皮性肿瘤的表达及与淋巴结转移相关研究

目的 :探讨细胞周期调控蛋白 P2 1CIP1 / WAF1 和细胞粘附分子 CD44 V6 在恶性卵巢上皮性肿瘤中的增殖、浸润、转移过程中的作用及相互关系。方法 :采用免疫组化方法 (im munohistochemical assay IHCA)检测 5 5例恶性卵巢上皮性肿瘤组织中 P2 1CIP1 / WAF1 蛋白和 CD44 V6 的表达。结果 :(1)恶性卵巢上皮性肿瘤中 P2 1CIP1 / WAF1总体阳性率为 5 5 .5 4% ,其中 期的阳性率为 2 1.43%低于 至 期的阳性率 6 5 .85 % (P<0 .0 5 ) ,伴有淋巴结转移的原发灶中的阳性率 31.5 7%明显低于无淋巴结转移的原发灶中的阳性率 6 6 .6 7% (P<0 .0 5 )。 (2 ) CD44 V6 在 到 期癌组织中表达阳性率差别无显著性 (P>0 .0 5 ) ,而在 、 期中强阳性 ( 、 )率 5 3.13%明显高于 、 期 13.0 4%(P<0 .0 5 ) ,在有淋巴结转移的原发灶中的强阳性率 (6 8.42 % )高于无淋巴结转移组 19.44 % (P<0 .0 1)。 (3) P2 1CIP1/ WAF1与 CD44 V6 在有淋巴结转移的原发灶中的表达呈负相关 (P<0 .0 5 )。结论 :P2 1CIP1 / WAF1 抑制恶性卵巢上皮性肿瘤增殖、浸润、转移 ,而 CD44 V6 作用相反     

大肠癌组织中HPV16、18E6,ras癌基因蛋白表达的研究

为探讨人乳头瘤病毒 16、18型感染与 p2 1ras癌基因协同在大肠癌发生机理中的作用 ,采用SP免疫组化技术 ,检测30例大肠腺瘤、10例腺瘤恶变、5 3例大肠腺癌和 30例正常大肠粘膜组织中HPV16、18E6 ,p2 1ras蛋白并分析其相互关系。结果显示 :腺瘤、腺瘤恶变和腺癌组中E6 ,p2 1ras的阳性表达分别为 36 .7% (11/ 30 )、40 .0 % (12 / 30 ) ,6 0 .0 % (6 / 10 )、70 .0 % (7/ 10 )和 5 4.7% (2 9/ 5 3)、71.7% (38/ 5 3) ,而正常组均呈阴性表达。在腺瘤组中 ,随着上皮不典型性增生程度的加重 ,E6、p2 1ras的阳性表达呈逐渐上升的趋势。腺瘤伴不典型性增生Ⅱ～Ⅲ级组中E6、p2 1ras阳性表达显著高于腺瘤伴不典型性增生Ⅰ级 (P <0 .0 5 )。此外 ,腺瘤、腺瘤恶变及腺癌组中E6与 p2 1ras的双阳性表达差异均有显著性 (P <0 .0 5 )。在有淋巴结转移组中 ,E6的阳性表达和E6与p2 1ras的双阳性表达均显著高于无淋巴结转移组 (P <0 .0 5 )。提示高危HPV16、18感染并在活化的ras癌基因的协同参与下 ,与本地区大肠癌的发生、发展过程密切相关 ,在腺瘤中同时检测E6、p2 1ras蛋白有可能成为大肠癌早期诊断的免疫学指标之一。     

大肠癌及癌旁粘膜p21~(ras)表达及意义

应用免疫组织化学方法对 12 8例人大肠癌及 32例不同距离癌旁粘膜进行研究。探讨 p2 1ras检测的临床病理学意义。结果 ,正常大肠粘膜、大肠癌、近癌旁粘膜、癌旁 1cm、2 cm、3cm及 5 cm粘膜 p2 1ras阳性率分别为 5 .0 % (1/ 2 0 )、5 2 .3% (6 7/ 12 8)、2 4.7% (18/ 73)、18.8% (6 / 32 )、15 .6 (5 / 32 )、9.4% (3/ 32 )及 9.4% (3/ 32 )。癌旁 3cm、5 cm粘膜的p2 1ras阳性率、阳性强度及分布均与正常粘膜相似 ,但癌旁 1cm、2 cm粘膜 p2 1ras阳性率较高且其中 5 0 %表达强度为(+ + )、(+ + + ) ,提示有 p2 1ras过表达现象。 p2 1ras表达与大肠癌临床病理因素无关。结论 :大肠癌中存在 p2 1ras过表达 ,且在癌旁 1cm、2 cm以内粘膜也存在 p2 1ras过表达可能 ,因此建议 ,在临床行大肠癌切除时 ,安全切缘至少在 3cm以上。     

Different types of structural variation in STRs: HumFES/FPS,HumVWA and HumD21S11

Summary Alleles of the STR systems HumFES/FPS, HumVWA and HumD21S11 were sequenced and analyzed. Sequence data revealed 3 different systems concerning the complexity of their sequence structure. HumFES/FPS belongs to the STR polymorphism with a simple repeat structure. Only 2 subtypes were found with a base substitution in the 5-flanking region and no variation in the repeat region. In the STR system HumVWA the sequence structure of the repeat region is more complex, because 2 tetranucleotide units TCTA and TCTG were present. Additionally allele 14 revealed a completely different sequence structure leading to a different electrophoretic mobility. The repeat region of HumD21S11 is compound in structure. The possibility of variation at 3 positions leads to the occurrence of microheterogeneities in fragments of apparent length. In the upper allele range alleles arise with an additional incomplete TA-repeat.     

The pharmacology of VA21B7: an atypical 5-HT3 receptor antagonist with anxiolytic-like properties in animal models

VA21B7 (3-[2-(4-piperonylpiperazinyl) indolyl] carboxaldehyde) was synthesized as a potential 5-HT₃ receptor antagonist. Even though VA21B7 showed a higher affinity towards 5-HT₃ receptors as compared to other receptors studied, it was not a potent 5-HT₃ receptor antagonist either in the periphery or in the brain. In a simple animal model of anxiety such as the two-compartment box in mice, a remarkable anxiolytic-like effect was found at doses of 2–500 µg/kg IP and also at low oral doses, in the microgram range. These drug doses did not produce any significant effect on spontaneous motor activity of mice. The anxiolytic profile of VA21B7 was further explored using other models of anxiety in rats such as the elevated plus-maze and punished-drinking. VA21B7 was compared with standard 5-HT₃ receptor antagonists such as ondansetron, tropisetron and granisetron, with the 5-HT_1A agent buspirone and with diazepam. In the plus-maze, VA21B7 showed an anxiolytic-like profile after doses of 0.25–0.5 mg/kg IP or 2–4 mg/kg PO which did not modify the number of total entries into the open and closed arms of the maze. Diazepam, granisetron and tropisetron were also effective in this test but not ondansetron and buspirone. VA21B7 was also able to release suppressed behaviour in the punished-drinking test. The dose-response curve was bell-shaped with a peak at 2–4 mg/kg. At variance with other studies, 5-HT₃ receptor antagonists also increased the number of shocks taken in this test and the dose-response curve was also bell-shaped. VA21B7 was not anticonvulsant like diazepam, its anxiolytic action in the light/dark test was not flumazenil-sensitive and there was no rebound anxiogenic effect on withdrawal from chronic VA21B7 treatment for 15 consecutive days. Moreover, VA21B7 was not amnesic like the benzodiazepines but low doses of 2–4 mg/kg reduced the memory deficits induced in rats by scopolamine. Much higher doses were necessary to decrease spontaneous motor activity in rats. Since VA21B7 appears to be well tolerated in rodents at high doses, we think that it is of potential interest as an anxiolytic in humans.