神经胶质瘤生物治疗的研究现状与进展

脑胶质瘤是颅内最常见的肿瘤。近年来关于神经胶质瘤的生物学研究取得了一定进展。首先是脑肿瘤干细胞的发现,其次是开展了肿瘤全基因组测序,这对于发现新的分子标记物是非常有用的,这些标记物(如IDH1基因突变)的发现甚至导致了基于分化和间质转化状况对神经胶质瘤的重新分类。此外,利用1p/19q标记及O6-甲基鸟嘌呤-DNA甲基转移酶基因(MGMT)是否被甲基化能为胶质瘤患者选择疗法和进行个性化药物治疗提供有意义的指导。作为治疗策略,替莫唑胺几年前已被确定为治疗脑胶质瘤的标准药物。最近在临床上贝伐单抗已开始用于脑胶质瘤的治疗。其他一些疗法目前还处于临床前开发和临床试验阶段,比如癌症疫苗、溶瘤腺病毒的研究等,这些潜在的疗法将来有可能成为胶质瘤治疗的手段或辅助手段。这些研究不仅揭示了神经胶质瘤的细胞起源,也为胶质瘤的诊断、治疗和预后判断提供了有用的信息和参考。     

Retroviral transduction and expression of the human alkyltransferase cDNA provides nitrosourea resistance to hematopoietic cells

Myelosuppression is the dose-limiting toxicity for nitrosourea chemotherapy. This toxicity predominantly involves modification of the O6 position of guanine with an alkyl moiety. The enzyme responsible for repair of O6-alkylguanine adducts, O6-alkylguanine-DNA alkyltransferase (alkyltransferase), is expressed at low levels in bone marrow (BM) cells. High alkyltransferase expression prevents the cytotoxicity and carcinogenicity of nitrosoureas in several transgenic and in vitro gene transfer models. We used gene transfer using a novel myeloproliferative sarcoma virus (MPSV) based retrovirus (vM5MGMT) to express the human alkyltransferase cDNA (MGMT) in human and murine hematopoietic cells. Transduced K562 cells had very high levels of alkyltransferase expression and significantly increased resistance to 1,3-bis (2- chloroethyl) nitrosourea (BCNU) as compared with untransduced K562 cells. Primary murine BM progenitors showed a high transduction efficiency with vM5MGMT and have increased BCNU resistance in vitro. After BM transplantation with vM5MGMT-transduced BM cells and BCNU treatment of these mice, BM, spleen and thymus had a 10- to 40-fold increase in alkyltransferase expression that persisted for at least 23 weeks posttransplantation. Progenitor cells procured from mice expressing high levels of alkyltransferase also had increased resistance to BCNU. Thus, an MPSV-based retroviral vector transduces mouse and human hematopoietic cells at high efficiency and results in high levels of gene expression both in vitro and in vivo. Overexpression of the alkyltransferase protein may protect hematopoietic progenitors from nitrosourea-induced myelosuppression.     

乳腺癌组织内雌激素受体新检测试剂的合成

1979年李善恒发明了雌激素受体检测试剂并在临床应用。为了寻找更有效、稳定、易得的受体检测试剂,我们曾以合成高分子化合物聚乙二醇代替原试剂中的牛血清白蛋白,以克服天然高分子化合物的不稳定性:另一方面,我们从雌激素的活性和改进合成路线着手,希望制备简便易得有效的试剂。     

医院集中式空调通风系统分区设计与控制院内感染的效应

医院中各种感染源与易感人群同时存在,极易发生医院感染,其中经空气导致的医院感染容易被忽视。分散于空气中的气溶胶与微生物以及运动的微粒是重要的感染传播媒介,而医院集中式空调的通风系统是医院环境中微粒最主要的来源,故此类型通风系统已成为经空气传播医院感染(并非只是呼吸道传染病)的重要传播途径。基于此,认为医院不应设置统一集中的中央空调通风系统,并依据流行病控制原则提出医院空调通风系统“分区”设计,即将医院内的污染区、清洁区、普通区的空调通风系统分别设置,区内根据实际工作需要增设必要的空气过滤设备,以有效控制经空气传播的医院感染发生。     

An epidemiological assessment of blood pressure determinants in an adolescent population of Nigerians

An epidemiological assessment of blood pressure determinants in a random sample of 254 Nigerian adolescents aged 6-17 years in Benin City, Nigeria, was conducted. None of the adolescents reported cigarette smoking. Only 2.6% of the males and 0% of the females were alcohol users. Socio-economic status of the children according to parental education revealed that approximately 23% of the mothers and 9.8% of the fathers received less than a secondary (high school) education. At the other end of the education spectrum, a college education was received by 64.1% and 30.8% of the fathers and mothers, respectively. Two percent of the females and 1.3% of the males either had systolic blood pressures of greater than or equal to 140 mmHg or diastolic blood pressures of greater than or equal to 90 mmHg. No significant blood pressure differences existed between the two sexes. Among the males, it was demonstrated that age, body mass index, and heart rate were significant independent predictors of systolic blood pressure, explaining 49% of the variance. Forty-seven per cent of systolic blood pressure variance was explained by age and heart rate, for females. It was interesting to note that age was the only independent predictor of diastolic blood pressure for both males and females after control for heart rate and body mass index.     

Hereditary xerocytosis: a report of six unrelated Spanish families with leaky red cell syndrome and increased heat stability of the erythrocyte membrane

Summary. Hereditary xerocytosis (HX) is a rare haemolytic disease due to dehydrated red blood cells (RBCs). A unique feature of this syndrome is that affected members often show normal or near normal haemoglobin levels despite clinical and laboratory evidence of mild to moderate haemolysis. The diagnostic clue is the association of markedly increased RBC Na⁺+K⁺ fluxes with low total cation (Na⁺ +K⁺) content. 11 patients of six unrelated families of Spanish origin with HX have been studied from clinical, genetical and biological points of view. In addition, we have investigated the sensitivity of RBC membrane to heat at three different incubation times (15, 30 and 60min) and two different temperature values (46°C and 49°C). Under these conditions control RBCs (50 normal subjects) exhibited at 49°C and 30min a maximum of 30% fragmented RBCs. This value increased to 80% after 60min of incubation. In contrast, patients with HX showed significantly lower percentages of fragmented RBCs at both 30 and 60min of incubation (maximum 10% and 30%, respectively). In an attempt to determine if increased heat stability was unique to HX RBCs, several other congenital membranopathies with haemolytic anaemia were also studied. The degree of fragmentation, except in one case of HPP (which was strongly increased), did not differ from the control group. Electrophoretic studies of membrane proteins performed in RBCs of all the patients with HX did not explain any qualitative nor quantitative abnormality.
In addition to its physiopathological interest, study of RBC heat stability, together with other haematological parameters (increased MCHC and decreased RBC osmotic fragility), may be useful for HX diagnosis, especially in laboratories which are not equipped to evaluate RBC membrane permeability.     

End-stage periventricular leukomalacia: MR evaluation

A prospective study was performed to assess the capabilities of magnetic resonance (MR) imaging in evaluation of end-stage periventricular leukomalacia (PVL) in six children, aged 31-54 months, in whom PVL had been documented by neurologic ultrasonography during the neonatal period. Eight children of similar age (four premature infants and four full-term infants) with normal neurologic development served as controls. A characteristic triad of PVL abnormalities was seen on MR images: (a) abnormally increased periventricular white-matter signal intensity on the first and second echo images of a T2-weighted sequence (repetition time = 2,000-2,400 msec, echo times = 20 or 30 and 80 msec), most commonly observed in the trigone regions of the lateral ventricles bilaterally; (b) marked loss of periventricular white matter in these regions of abnormal signal intensity, predominantly in the periatrial regions; and (c) compensatory focal ventricular enlargement adjacent to regions of abnormal signal intensity. In patients with the classic periatrial distribution of PVL lesions, general correlation between the degree of neurologic impairment and the severity of MR abnormalities was demonstrated. MR imaging was useful in detecting subtle forms of PVL in cases in which neurologic damage was subclinical.