胶质瘤中LGI 1的突变及微卫星不稳定性研究

目的 为了检测人脑胶质瘤组织及胶质瘤细胞系LGI 1基因编码区中有无碱基突变及微卫星不稳定性(MSI)和杂合性缺失(LOH).方法 收集30例胶质瘤标本,2例脑膜瘤、2例瘤旁及2例颅脑损伤内减压脑组织标本及体外培养5个脑胶质瘤细胞系.提取组织标本及培养细胞基因组DNA.设计特异性引物分别扩增LGI 1各外显子序列,采用SSCP银染分析;扩增LGI 1微卫星序列,凝胶电泳银染分析;发现异常泳动条带进行DNA序列分析.结果 ①PCR-SSCP分析琼脂糖凝胶电泳检测有1例Ⅱ级胶质瘤标本未检测到第1 a外显子处扩增产物以及Ⅱ、Ⅲ级各1例胶质瘤标本均未检测到第8 c外显子处扩增产物.未在30例胶质瘤标本和4个脑胶质瘤细胞系中检测到电泳条带异常,在细胞系TJ905第5外显子处检测到电泳条带异常,经DNA测序分析证实确有突变.②在30例胶质瘤标本及5个细胞系中均未检测到MSI和LOH.结论 基因突变及MSI和LOH可能不是LGI 1在胶质瘤恶性进展过程中失活的主要原因.     

Clinical pathology of primitive gliomas in the cerebrum

Summary To clarify the biological features of primitive gliomas in the cerebrum and clearly distinguish them from malignant or anaplastic gliomas and glioblastomas, we studied eight cases clinically and pathologically. Our evaluations included immunohistochemical and electron microscopic observations. We divided the patients into two groups, children and young adults. Most tumours appeared as ring-like, enhanced masses on computed tomography and avascular or ring-like, vascular masses on angiography. Macroscopically, the tumours were well demarcated and contained cysts. Ocassionally we found tumour dissemination. Microscopically, the tumours were composed of small, round cells without remarkable structural features. Ependymal, astroglial, and oligodendroglial differentiation was evident, in varying proportions; tumours in which the differentiated areas constituted more than half of the mass were classified as poorly differentiated gliomas. By these criteria, this series comprised four undifferentiated and four poorly differentiated gliomas. Cell anaplasia and polymorphism were rare in both undifferentiated and differentiated areas of the tumours. Immunohistochemical and electron microscopic examinations also revealed glial differentiation. These primitive gliomas appear to be biologically similar, but not identical, to cerebellar medulloblastomas. In this series, five patients died because of recurrence or dissemination. Whole brain and spinal irradiation should be considered after total or subtotal surgical removal.     

Ultrastructure of a two-cell human embryo

Summary A two-cell human embryo recovered from the Fallopian tube 82 h following the LH peak in plasma and 37 h after a single episode of intercourse was examined by transmission electron microscopy. At the time of recovery the embryo was denuded of cumulus cells, and both the zona pellucida and the two adjoining blastomeres were intact. The finding of two polar bodies in the perivitelline space, two nucleated blastomeres and remnants of the fertilizing sperm tail within the cytoplasm of one of them, were considered as evidences that the embryo was normally fertilized. Among the most compicuous features found were the presence of very distinct desmosome-like structure between blastomeres, and the cytoplasmic cell organelles distribution in three areas referred as: a sub-cortical, a middle and a perinuclear bands. An outstanding feature was the extensive blebbing of the nuclear envelope. In general, the features seem to correspond to a normally developing two-cell embryo undergoing cleavage at a normal rate.     

用显微分光光度计对几种不同类型肺癌癌细胞DNA含量的初步观测

本文用显微分光光度计对39例手术切除的不同组织学类型的人体肺癌标本癌细胞核的DNA含量进行了测量。其中高、中、低分化的鳞癌分别为3、6和5例;高、中、低分化的腺癌分别为3、5和5例;未分化癌大细胞型和小细胞型各为3例和6例。结果发现各类型肺癌的DNA含量均有统计学上的差异(P<0.01)。各DNA含量直方图的峰值部位及分布范围亦不同。从而提示了根据DNA含量的不同,可能有助于肺癌组织学类型及其分化程度的判别:而DNA含量直方图对肺癌类型的判别亦可能是有益的。     

Sex differences in plasma cocaine levels and subjective effects after acute cocaine administration in human volunteers

Gender differences after acute cocaine administration have received little attention in spite of the fact that males and females respond differently to many drugs. Seven male and seven female occasional cocaine users received both an intranasal dose of cocaine hydrochloride (0.9 mg/kg) and placebo powder in a randomized order and reported subjective effects via an instrumental joystick device and various questionnaires. Blood samples were withdrawn at 5-min intervals to assess pharmacokinetic differences. Male subjects achieved the highest peak plasma cocaine levels (144.4 ± 17.5 ng/ml), detected cocaine effects significantly faster than females and also experienced a greater number of episodes of intense good and bad effects. Women studied during the follicular phase of their menstrual cycle had peak plasma cocaine levels of 73.2 ± 9.9 ng/ml, which was significantly higher than when they were studied during their luteal phase (54.7 ± 8.7 ng/ml), but there were no differences in their subjective reports of cocaine effects. In spite of the different cocaine blood levels and subjective effects, peak heart rate increases did not differ between males and females suggesting that women may be more sensitive than males to the cardiovascular effects of cocaine. These data suggest that there are significant gender and menstrual cycle differences in the response to acute intranasal cocaine administration and these differences may have implications for the differential abuse of this drug.This paper is dedicated to Xavier Lamas, MD, PhD, who lost his life while ascending Mt. Everest, August 1995     

PET examination of [11C]NNC 687 and [11C]NNC 756 as new radioligands for the D1-dopamine receptor

The benzazepines NNC 687 and NNC 756 have in animal studies been described as selective D₁-dopamine receptor antagonists. Both compounds have been labeled with¹¹C for examination by positron emission tomography (PET). In the present study central receptor binding was studied in monkeys and healthy men. After IV injection of both radioligands in Cynomolgus monkeys radioactivity accumulated markedly in the striatum, a region with a high density of D₁-dopamine receptors. This striatal uptake was displaced by high doses of the selective D₁-antagonist SCH 23390 (2 mg/kg) but not by the 5HT₂-antagonist ketanserin (1.5 mg/kg) or the selective D₂-antagonist raclopride (3 mg/kg). The cortical uptake after injection of [¹¹C]NNC 687 was not reduced in displacement experiments with ketanserin. The cortical uptake of [¹¹C]NNC 756 was reduced in displacement and protection experiments with ketanserin by 24–28% (1.5 mg/kg), whereas no reduction could be demonstrated on striatal uptake. In healthy males both compounds accumulated markedly in the striatum. For [¹¹C]NNC 687 the ratio of radioactivity in the putamen to cerebellum was about 1.5. For [¹¹C]NNC 756 the ratio was about 5. This ratio of 5 for [¹¹C]NNC 756 is the highest obtained so far for PET radioligands for the D₁-dopamine receptor.     

The potential of topoisomerase I inhibitors in the treatment of CNS malignancies: report of a synergistic effect between topotecan and radiation

Summary Despite innovations in imaging, surgery, and radiation therapy, local failure remains the principle clinical problem in most CNS malignancies. To date, chemotherapy has not made a major impact in the treatment of most adult CNS tumors. The inroads made by chemotherapy in pediatric CNS malignancies suggest that novel drugs, or drug combinations, may improve therapy. Topoisomerase I (Topo I) inhibitors are a relatively new group of chemotherapy drugs with a novel mechanism of action. Drugs in this group currently undergoing clinical trials are the Camptothecin analogues Topotecan, CPT-11, and 9-aminocamptothecin. There is substantial preclinical and some clinical evidence to suggest that these drugs could be useful in the treatment of CNS malignancies. Preclinical studies with the water soluble Topo I inhibitor, Topotecan, demonstrate antineoplastic activity in a variety of CNS malignancies. In addition, Topotecan has good CNS penetration in primates, and recent preliminary phase I and II clinical trials of Topotecan in pediatric and adult CNS malignancies have been promising. In this paper, we describe the unique mechanism of action, antineoplastic activity, and radiosensitizing properties of Topo I inhibitors. We present the first report demonstrating potentiation of radiation lethality by Topotecan in a human glioma (1354) cell line. The dose enhancement ratio was 3.2 at 10% survival. Thus, there is evidence to suggest that Topo I inhibitors may be beneficial in the treatment of CNS neoplasms on the basis of their antineoplastic activity alone, as well as their radiosensitizing effects. Two clinical trials which utilize concurrent Topotecan and radiation in the treatment of pediatric and adult CNS malignancies are discussed.     

辐射诱发淋巴细胞凋亡生成与抑制作用研究

研究了辐射诱发的人外周血淋巴细胞凋亡生成，以及水溶性维生素Ｅ类似物－Ｔｒｏｌｏｘ对辐射诱导人外周血淋巴细胞凋亡的抑制作用。照后３０分钟内Ｔｒｏｌｏｘ能有效地阻抑ＤＮＡ片段形成，而在照前或受照中加入Ｔｒｏｌｏｘ均不能抑制ＤＮＡ片段形成，揭示Ｔｒｏｌｏｘ并不是通过清除照射过程中产生的自由基而起作用。照后３０分钟内加Ｔｒｏｌｏｘ，２小时后撤去，同样能抑制ＤＮＡ片段形成，表明Ｔｒｏｌｏｘ能不可逆地阻抑细胞凋亡早期的＂关键＂事件。     

链置换式扩增检测羊水中巨细胞病毒DNA

目的：介绍一种简便快速准确检测羊水中ＣＭＶ－ＤＮＡ的改良ＰＣＲ－链置换式扩增用于诊断胎儿先天感染ＣＭＶ。方法，将组成套式ＰＣＲ的外内两对引物按照一定比例（外：内＝１：５０－１００）加在同一试管中一次扩增羊水和胎儿组织中ＣＭＶ－ＤＮＡ。结果：９０例异常孕产史的孕妇羊水检测ＣＭＶ－ＤＮＡ，阳性率为３８．９％（３５／９０），其中合并染色数目异常２例（４７，ＸＹＹ和４７，ＸＸ，＋２１）（已引产）核型及染色