A virosomal vaccine against candidal vaginitis: immunogenicity, efficacy and safety profile in animal models

A novel vaccine (PEV7) consisting of a truncated, recombinant aspartyl proteinase-2 of Candida albicans incorporated into influenza virosomes was studied. This vaccine candidate generated a potent serum antibody response in mouse and rat following intramuscular immunization. Anti-Sap2 IgG and IgA were also detected in the vaginal fluid of rats following intravaginal or intramuscular plus intravaginal administration. In a rat model of candidal vaginitis, PEV7 induced significant, long-lasting, likely antibody-mediated, protection following intravaginal route of immunization. PEV7 was also found to be safe in a repeated-dose toxicological study in rats. Overall, these data provide a sound basis to envisage the clinical development of this new candidate vaccine against candidal vaginitis.     

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.     

Hypothalamic obesity in the weanling rat: effect of diet upon hormonal and metabolic alterations

Weanling rats with ventromedial hypothalamic (VMN) lesions were studied on diets varying in carbohydrate and fat content and after 48 hr of starvation to determine dietary effects on the specific endocrine-metabolic alterations associated with this model of experimental obesity. Neither food intake nor the increased carcass fat of VMN rats was affected by diet, though with starvation VMN rats lost more fat and less lean tissue than did controls. Hyperinsulinemia in VMN rats persisted on all diets but disappeared after starvation, at which time moderate hypoglycemia developed. Hypertriglyceridemia was present in VMN rats on fat containing diets but not on a fat-free diet unless the animals were subsequently starved. Increased glucose oxidation and conversion to lipid by adipose tissue of VMN rats was independent of diet and persisted during starvation. The rate of glycogen synthesis was not increased. Palmitate oxidation by VMN adipose tissue was reduced in fed animals but increased in starved animals when compared to similarly treated controls. The observed dissociation of hyperinsulinemia and hypertriglyceridemia as a consequence of dietary alteration and starvation suggests independent pathogenetic mechanisms for these variables. Similarly, persistence of enhanced glucose utilization by adipose tissue during starvation, and selective enhancement of glucose oxidation and lipid but not glycogen synthesis from glucose suggests the presence of a primary defect in VMN adipose tissue metabolism, at least partly independent of hyperinsulinemia.     

Pair-feeding of sham-operated controls to rats with dorsomedial hypothalamic lesions: new evidence for an 'organismic' set point

Weanling male Sprague-Dawley rats received electrolytic lesions in the dorsomedial hypothalamic nuclei (DMNL rats) and sham operations, respectively, and were maintained on lab chow ad libitum for 23 days (Expt. 1) and 55 days (Expt. 2). Following this period, one group of sham-operated controls was pair-fed to the DMNL rats, which were hypophagic compared to a second sham-operated group that was fed ad libitum. This period lasted 27 days (Expt. 1) and 24 days (Expt. 2). Although pair-fed controls were heavier than DMNL rats, they showed normal food utilization (EFU) in Expt. 1 and reduced EFU in Expt. 2. Pair-fed controls also had decreased carcass fat, hypoglycemia, hypoinsulinemia, hypotriglyceridemia and enhanced in vitro epididymal fat pad glucose oxidation when compared to DMNL rats. These data suggest that pair-fed controls cannot cope as efficiently with the reduced influx of substrate as do DMNL rats. Evidently, the reduced amount of food that DMNL rats spontaneously eat is adequate for their reduced body size, whereas this is not the case in the pair-fed controls. This is taken as evidence for a harmonious readjustment by DMN lesions of both body size and food intake and the underlying homeostatic processes and supports our concept of an 'organismic' set point that has been released by the DMN lesions.     

Normal catch-up growth in rats severely food-restricted prior to lesions of the dorsomedial hypothalamic nucleus: the first 48 hours

Following a brief period of ad lib (AL) feeding, 45-day-old male Sprague-Dawley rats were either fed AL or food-restricted (REST) for 21 days to 50% of the intake of the AL rats. At this time, some AL and some REST rats received electrolytic lesions in the dorsomedial hypothalamic nuclei (DMNL), whereas other AL and REST rats were sham-operated (CON). Following this, all rats were refed (REF) AL and killed two days later. At this time, DMNL-REST + REF and DMNL-AL weighed as much as CON-REST + REF and CON-AL, whereas the body weight of the DMNL-AL group began to separate from the CON-AL group; carcass lipid and protein were normal among the groups. DMNL-AL laid down more % lipid and % protein/g food eaten than CON-AL; this was not the case in the REST + REF groups. DMNL-AL were hypophagic vs. CON-AL, but DMNL-REST + REF ate as much as CON-REST + REF. Compared to DMNL-AL, DMNL-REST + REF increased their food intake more than four-fold and also utilized food energy more efficiently than DMNL-AL rats. Epididymal fat pads and kidneys were smaller in REST + REF vs. AL groups, irrespective of brain manipulation. Plasma glucose and growth hormone were normal among the groups, but plasma insulin concentrations were higher in REST + REF DMNL and CON groups vs. DMNL-AL and CON-AL, respectively. Glucose incorporation into epididymal fat pad lipid and CO2 and liver lipid was elevated in REST-REF groups vs. respective AL groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

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。