单克隆抗体与超抗原结合物介导的T细胞抗肿瘤作用研究进展

超抗原(SAg)是一类能高效地刺激T细胞增殖并且使之释放大量细胞因子的细菌或病毒产物.SAg与抗肿瘤单克隆抗体(McAb)的偶联物或者利用基因工程手段制成的它们的融合蛋白对MHCⅡ类分子阳性或阴性的肿瘤细胞都有强大的杀伤作用.体外细胞毒实验和动物体内实验的研究结果表明,它很有可能成为一种有效的新型肿瘤免疫导向治疗剂.但是目前尚未见临床应用的报道.本文综述了用McAb与SAg结合物介导的T细胞对肿瘤进行免疫导向治疗的实验研究进展.     

Impairment in short-term but enhanced long-term synaptic potentiation and ERK activation in adult hippocampal area CA1 following developmental thyroid hormone insufficiency.

Thyroid hormones are critical for the development and maturation of the central nervous system. Insufficiency of thyroid hormones during development impairs performance on tasks of learning and memory that rely upon the hippocampus and impairs synaptic function in young hypothyroid animals. The present study was designed to determine if perturbations in synaptic function persist in adult euthyroid animals exposed developmentally to insufficient levels of hormone. Pre- and postnatal thyroid hormone insufficiency was induced by administration of 3 or 10 ppm propylthiouracil (PTU) to pregnant and lactating dams via the drinking water from gestation day (GD) 6 until postnatal day (PN) 30. This regimen produced a graded level of hormonal insufficiency in the dam and the offspring. Population spike and population excitatory postsynaptic potentials (EPSP) were recorded at the pyramidal cell layer and the stratum radiatum, respectively, in area CA1 of hippocampal slices from adult male offspring. PTU exposure increased baseline synaptic transmission, reduced paired-pulse facilitation, and increased the magnitude of the population spike long-term potentiation (LTP). Phosphorylation of the extracellular signal-regulated kinases (ERK1 and ERK2) was increased as a function of LTP stimulation in slices from PTU-exposed adult animals. On the other hand, no differences in the basal levels of synaptic proteins implicated in synaptic plasticity (total ERK, synapsin, growth-associated protein-43, and neurogranin) were detected. These results reinforce previous findings of persistent changes in synaptic function and, importantly extend these observations to moderate levels of thyroid hormone insufficiency that do not induce significant toxicity to the dams or the offspring. Such alterations in hippocampal synaptic function may contribute to persistent behavioral deficits associated with developmental hypothyroidism.     

武汉东湖微囊藻毒素污染及其在鱼体内的动态研究

目的　了解武汉东湖微囊藻毒素污染水平及其在鱼体内的富集状况。方法　 2 0 0 0年 7月和 10月 ,采集了湖边和湖中的水样和鱼样 ,用ELISA法对样品的微囊藻毒素 (MC)进行测定。结果　各采样点都有蓝藻的污染 ,蓝藻已成为东湖的优势藻种。 10月份水中MC含量 ,显著高于 7月份水中MC含量 (P <0 0 5 ) ;肝脏中MC含量 ,显著高于肌肉中MC含量 (P<0 0 5 )。     

血细胞分析仪的工作原理及其近期发展

本文简要介绍了血细胞分析仪的主要工作原理，各主要厂家在血细胞分析仪上采用的白细胞分类技术及业界的技术进展。     

女性肾上腺性征异常症

目的 探讨女性假两性畸形的诊断和治疗的时机及方法。方法 回顾性分析近23年来收治的31例患儿的诊疗资料。1～6岁19例，7～14岁12例。性染色体均为46，XX。腕骨骨龄大于实际年龄的18例。出生后均见阴蒂肥大，27例为尿生殖窦单一开口，4例分别见到尿道和阴道口，半数已长出阴毛、声粗、痤疮，最小者2岁，3例14岁患儿身高不足150cm。行B超检查及尿生殖窦造影的病例均有正常女性生殖道。失盐型3例，在新生儿期出现危象而确诊。结果 剖腹探查的9例有正常卵巢及内生殖道。26例作了阴蒂缩短成形或肥大阴蒂切除，小阴唇成形。除1例外，其余30例均在确诊后接受内科药物治疗。结论 典型的女性肾上腺性征异常诊断虽不难，但就诊年龄多较晚，药物治疗滞后，对患儿的生理和心理有严重的负面影响。典型患儿不必作剖腹探查。失盐型患儿多在新生儿期出现危象，应尽早诊疗。     

儿童血管迷走性晕厥诊断程序的卫生经济学评价

目的对儿童血管迷走性晕厥(VVS)的传统诊断程序与新诊断程序进行卫生经济学评价。 方法采用回顾分析方法，根据不同的诊断程序(即传统诊断程序和新诊断程序)，将1995年1月至2005年5月北京大学第一医院儿科确诊的81例VVS患儿分为2组，分别计算其就诊费用、检查费用、住院日、确诊日等，运用经济学最小成本分析法进行评价。 结果新诊断程序的平均就诊费用比传统诊断程序少耗费1668.80元；新诊断程序的平均就诊检查费用比传统诊断程序少耗费1413.30元。 结论新诊断程序对确诊儿童血管迷走性晕厥具有良好的经济学效益，值得临床推广。     

Insights into oxazaphosphorine resistance and possible approaches to its circumvention.

The oxazaphosphorines cyclophosphamide, ifosfamide and trofosfamide remain a clinically useful class of anticancer drugs with substantial antitumour activity against a variety of solid tumors and hematological malignancies. A major limitation to their use is tumour resistance, which is due to multiple mechanisms that include increased DNA repair, increased cellular thiol levels, glutathione S-transferase and aldehyde dehydrogenase activities, and altered cell-death response to DNA damage. These mechanisms have been recently re-examined with the aid of sensitive analytical techniques, high-throughput proteomic and genomic approaches, and powerful pharmacogenetic tools. Oxazaphosphorine resistance, together with dose-limiting toxicity (mainly neutropenia and neurotoxicity), significantly hinders chemotherapy in patients, and hence, there is compelling need to find ways to overcome it. Four major approaches are currently being explored in preclinical models, some also in patients: combination with agents that modulate cellular response and disposition of oxazaphosphorines; antisense oligonucleotides directed against specific target genes; introduction of an activating gene (CYP3A4) into tumor tissue; and modification of dosing regimens. Of these approaches, antisense oligonucleotides and gene therapy are perhaps more speculative, requiring detailed safety and efficacy studies in preclinical models and in patients. A fifth approach is the design of novel oxazaphosphorines that have favourable pharmacokinetic and pharmacodynamic properties and are less vulnerable to resistance. Oxazaphosphorines not requiring hepatic CYP-mediated activation (for example, NSC 613060 and mafosfamide) or having additional targets (for example, glufosfamide that also targets glucose transport) have been synthesized and are being evaluated for safety and efficacy. Characterization of the molecular targets associated with oxazaphosphorine resistance may lead to a deeper understanding of the factors critical to the optimal use of these agents in chemotherapy and may allow the development of strategies to overcome resistance.     

鹅掌藤中三萜类化合物的分离与鉴定

目的研究五加科鹅掌柴属植物鹅掌藤(Schefflera arboricola)枝茎的化学成分.方法采用柱色谱分离,通过理化数据和光谱分析确定化合物的结构.结果从鹅掌藤乙酸乙酯提取物中分离得到7个三萜化合物,分别鉴定为羽扇醇(1)、桦木酸(2)、3-epi-betulinic acid(3)、齐墩果酸(4)、3-乙酰齐墩果酸(5)、mesembryanthemoidigenic acid(6)、quinatic acid(7).结论化合物1、5、6、7为首次从该属植物中分得.     

Gatifloxacin inducing apoptosis of stromal fibroblasts through cross-talk between caspase-dependent extrinsic and intrinsic pathways

AIM: To reveal the cytotoxicity and related mechanisms of gatifloxacin (GFX) to stromal fibroblasts (SFs) in vitro. METHODS: SFs were treated with GFX at different concentrations (0.009375%-0.3%), and their viability was detected by MTT method. The cell morphology was observed using light/transmission electron microscope. The plasma membrane permeability was measured by AO/EB double-staining. Then cell cycle, phosphatidylserine (PS) externalization, and mitochondrial transmembrane potential (MTP) were analyzed by flow cytometry. DNA damage was analyzed by electrophoresis and immunostaining. ELISA was used to evaluate the caspase-3/-8/-9 activation. Finally, Western blotting was applied for detecting the expressions of apoptosis-related proteins. RESULTS: Morphological changes and reduced viability of GFX-treated SFs demonstrated that GFX above 0.009375% had cytotoxicity to SFs with dependence of concentration and time. GFX-treating cells also showed G1 phase arrest, increased membrane permeability, PS externalization and DNA damage, which indicated that GFX induced apoptosis of SFs. Additionally, GFX could activate the caspase-8, caspase-9, and caspase-3, induce MTP disruption, downregulate B-cell leukemia-2 (Bcl-2) and B-cell leukemia-XL (Bcl-XL), and upregulate Bcl-2 assaciated X protein (Bax), Bcl-2-associated death promoter (Bad), Bcl-2 interacting domain (Bid) and cytoplasmic cytochrome C in SFs, suggesting that caspase-dependent extrinsic and intrinsic pathways were related to GFX-contributed apoptosis of SFs. CONCLUSION: The cytotoxicity of GFX induces apoptosis of SFs through triggering the caspase-dependent extrinsic and intrinsic pathways.