人精子染色体改良技术及其应用

课题研究提供了改良的人精子染色体直接制备，Ｇ显带核分析技术。在对８０例对象的人精子染色体直接制备，Ｇ显带核型分析中，成功率为６２．５％，较Ｔｅｍｐｌａｄｏ方法的成功率（５８．１％）进一步提高。通过对正常人，不育，流产对象的男性精子染色体研究，发现精子染色体数目和结构畸变率分别为：正常人２．３％和０％，不育１４．０％和４．８％，流产组４．５％和２．４％，不育和流产组的畸变率较正常人增加。在对５例染色     

Cell proliferation in human tumours growing in nude mice: renal cell carcinomas,larynx and hypopharynx carcinomas

Summary Cell proliferation of 51 human renal cell carcinomas and 9 larynx and hypopharynx carcinomas has been studied in vitro and using xenotransplants. The proliferative activity ([³H]thymidine labelling index) increases during the first passages in nude mice and then remains almost constant throughout subsequent passages. A comparison of cell kinetic parameters of 8 human renal cell carcinomas, 1 hypopharynx and 2 larynx carcinomas, with data of xenografts and of human tumours in situ published up to now, shows that the cell kinetic parameters of human tumour xenografts presently studied range between those of human tumours in situ and those of autochthonous or transplantable mouse tumours. S-phase durations and potential doubling times are considerably shorter in xenotransplants than in human tumours in situ, whereas the cycle time is about the same. This means that the growth fraction increases considerably after xenotransplantation. This change of human tumour cell proliferation after transplantation into nude mice should be kept in mind if one wishes to draw conclusions from the nude mouse model on conditions in human beings, particularly with respect to therapeutic regimens, which are frequently tested in the nude mouse model.Abbreviations used RCC renal cell carcinoma - HPC larynx or hypopharynx carcinoma - LI labelling index - PLM percentage of labelled mitoses - t _s S-phase duration - t _c cycle time - t _pot potential doubling time This work was supported by the Deutsche Forschungsgemeinschaft (Ma 876/2-1)     

Why Are Human Cells Resistant to Malignant Cell Transformation in vitro?1

Transformation of human cells, both induced and spontaneous, is an extremely rare event, whereas rodent cells are relatively easily transformed when treated with a single carcinogenic agent. The present review addresses the question of why human cells are resistant to malignant transformation in vitro. To facilitate understanding of the problem, the process of transformation is divided operationally into two phases, i.e. phase I, immortalization; and phase II, malignant transformation. In human cells, one-phase transformation, i.e., the consecutive occurrence of phases I and II due to the action of a single carcinogenic agent, is observed only rarely. Once human cells are immortalized, however, malignant transformation by chemical carcinogens or oncogenes proceeds, suggesting that for human cells, phase I immortalization is a prerequisite for such transformation to take place. To date, about 20 papers have been published describing protocols for the two-phase transformation of a variety of human epithelial cells and fibroblasts. In most experiments, SV40, human papilloma viruses and their transforming genes are utilized for induction of phase I (immortalization) followed by the use of chemical carcinogens or activated oncogenes for induction of phase II (malignant transformation). Possible mechanisms that would render human cells refractory to transformation are discussed below.     

Two tyrosinase nonapeptides recognized on HLA-A2 melanomas by autologous cytolytic T lymphocytes

A number of cytolytic T lymphocyte (CTL) clones derived from several melanoma patients have been found to recognize a majority of melanomas from HLA-A2 patients. We have reported previously that two such CTL clones recognize a product of the tyrosinase gene that is presented by HLA-A2. Here we show that one of these CTL clones recognizes a peptide encoded by the first nine amino acids of the putative signal sequence of tyrosinase. The other CTL clone recognizes a different tyrosinase peptide corresponding to amino acids 368–376. Both peptides contain consensus motifs of HLA-A2 binding peptides.     

Codon 178 mutation of the human prion protein gene in a German family (Backer family): sequencing data from 72-year-old celloidin-embedded brain tissue

Familial Creutzfeldt-Jakob disease was first described in a family from northern Germany in the 1920s (Backer family). PCR amplification of DNA extracted from brain tissue embedded in celloidin 72 years ago shows a GAC to AAC substitution at codon 178 of the prion protein gene. This mutation is associated with fatal familial insomnia and familial Creutzfeldt-Jakob disease in a number of families of diverse ethnic background.     

人脑胶质瘤中P53和VEGF 的表达及意义

目的 探讨胶质瘤组织中血管内皮生长因子(VEGF)和P53蛋白的表达及其临床意义。方法 应用免疫组织化学技术对50例胶质瘤组织进行P53、VEGF表达的检测。结果 P53、VEGF的表达均随胶质瘤病理级别的升高而升高。Ⅰ～Ⅳ级病理分级中P53阳性率分别为22．22％(4／18)，65％(13／20)，75％(9／12)；VEGF阳性率分别为27．78％(5／18)，90％(18／20)，100％(12／12)。P53、VEGF的表达均与胶质瘤病理分级显著相关(P＜0．01)，P53和VEGF阳性表达符合率为76％(38／50)，两者的表达有显著性相关(P＜0．01)。结论 P53和VEGF蛋白的表达是判断胶质瘤生物学行为的重要指标；胶质瘤组织突变的P53基因可上调VEGF的表达，促进血管生成，进而影响胶质瘤的进展。     

Anticipatory postural adjustments during self-paced and reaction-time movements

We studied the changes in the anticipatory postural adjustments (APAs), associated with dropping a load from extended arms and during fast bilateral shoulder flexion movements, when movements were performed in a self-paced manner and under a simple reaction-time instruction. The latter instruction applied time pressure and did not allow the regular pattern of APAs to be used. In particular, the following questions were asked: (1) are there changes in the relative timing of APAs under the reaction time condition; (2) are changes in the relative timing of APAs associated with changes in APAs themselves; (3) can different postural strategies be used to maintain stability under self-paced and reaction time conditions; and (4) are changes in APAs related to actual reaction time or to a change in the instruction? In particular, under reaction-time conditions, APAs occurred later in time, typically simultaneously with the initiation of the focal movement. Additional changes in electromyographic (EMG) patterns in postural muscles included an increase in the amplitude of EMG bursts and “speeding-up” some of the tri-phasic patterns in postural dorsal-ventral muscle pairs. This was accompanied by a smaller early shift of the center of pressure followed by its more rapid delayed displacement. There was considerable variability in the changes of EMG and dynamic characteristics across subjects. Some of the changes in the EMG patterns in postural muscles depended on actual reaction time, while others were related to a change in the instruction and occurred even if actual reaction times were long enough to allow for the typical self-paced APA patterns to occur. These findings can be interpreted as supporting the parallel control hypothesis for the focal movement and postural adjustments. Alternatively, they can be interpreted within a framework that implies the generation of a single control function, which is transformed into two components, one directed at the focal muscles/joints and the other directed at postural muscles/joints.     

β-N-Acetylhexosaminadases in human cerebrospinal fluid and serum of patients with multiple sclerosis

β-N-Acetylhexosaminidase activity and isoenzyme have been investigated in normal human cerebrospinal fluid and that of patients with multiple sclerosis. β-N-acetylhexosaminidase activity in normal cerebrospinal fluids has been resolved into five components. The major component was in a form that eluted from DEAE cellulose at the same salt concentration as hexosaminidase As, the isoenzyme previously identified in human serum. Cerebrospinal fluid from patients exhibited a different isoenzyme profile, showing a remarkable increase in a form having a pI which was more acidic than that of As. These changes have a potential use in the diagnosis and further biochemical characterization of multiple sclerosis.     

人脑胶质瘤中cyclinD1/bcl-1和p27/kip1的表达与病理、预后的相关性研究

目的 :研究cyclinD1 bcl 1和p2 7 kip1在脑胶质瘤中表达及其与病理分级和患者预后的关系。方法 :用免疫法组化技术对 4 8例不同恶性程度 (WHO分类法 )的脑胶质瘤组织和 12例非肿瘤组织中cyclinD1 bc1 1和p2 7 kip1蛋白的表达作了检测 ,用图像分析系统定量分析 ,并与临床资料紧密相联系进行统计学处理。结果 :两种蛋白的免疫反应复合物定位于细胞核。其在脑胶质瘤中的阳性表达都高于非肿瘤组织 (P <0 0 5 ) ,cyclinD1 bcl 1阳性颜色的数量和强度都随肿瘤的恶性程度升高而增加 (P <0 0 5 ) ,相反p2 7 kip1阳性染色的数量和强度都随肿瘤的恶性程度升高而降低 (P <0 0 5 )。cyclinD1 bcl 1的高表达或 和p2 7 kip1的低表达预示着预后差。结论 :CyclinD1 bcl 1和p2 7 kip1的异常表达可能与脑胶质瘤的发生发展密切相关 ,二者可能有协同作用。二者的表达都可作为判断预后的一个指标     

Temporal Lobe Epileptogenesis and Epilepsy in the Developing Brain: Bridging the Gap Between the Laboratory and the Clinic. Progression, But in What Direction?

Summary:  The origins of human mesial temporal lobe epilepsy and hippocampal sclerosis are still not well understood. Hippocampal sclerosis and temporal lobe epileptogenesis involve a series of pathologies including hippocampal neuronal loss and gliosis, axonal reorganization, and maybe hippocampal neoneurogenesis. However, the causality of these events is unclear as well as their relation to the factors that may precipitate epileptogenesis. Significant differences between temporal lobe epileptogenesis in the adult and immature brain may require differential approaches. Hereditary factors also may participate in some cases of hippocampal sclerosis. The key point is to identify the significance of these age-dependent changes and to design preventive treatments. Novel strategies for the prevention and treatment of mesial temporal lobe epilepsy and hippocampal sclerosis may include rational use of neuroprotective agents, hormonotherapy, immunizations, and immunotherapy.