T辅助细胞在疫苗研制中的作用

发展感染性疾病疫苗之关键挑战在于利用确定的抗原以刺激产生能引起保护作用的合适的免疫反应。肽类疫苗的运用得到了极大的关注，其意义在于，已知不同的多表位构成单一结构以诱导出所希望的免疫反应所表现出的灵活性。这一般比利用减毒的活疫苗要安全并且相对而言比制造亚单位疫苗要容易。然而，多肽疫苗的发展面临巨大挑战。这一方法在诱导遗传背景复杂的人群免疫反应方面受到限制，这与主要组织相溶性复合物(MHC)多态性有关。因同样的理由，肽类免疫应答常因缺乏适当的辅助T淋巴细胞(HIL)而引导出不充分的细胞毒素T淋巴细胞(CTL)和抗体反应。另一个运用线性肽链结构的可能缺点是：为了引导出合适抗体反应，表面免疫球蛋白受体簇对于激活静息的B细胞就成为必须因素。由WHC多肽性引起的问题可由运用不加区别的T细胞表位来解决。从麻疹病毒F蛋白(氨基酸288到302)中得到的不加区别的T细胞表位和鼠的确定结合在多种MHC分子上的辅助T细胞表位(v1EB，aa191-209)已被定性并且被用于能极大激发免疫应答的结构中，以克服单一限制型免疫应答的缺陷。合成的，非自然Pan DR表位(PADRE)具有退化的结合几种通常HLA—DR的能力，能以绝对效价和抗体反应质量两种形式来增强激发短肽链的免疫应答。另外，一些所谓的从流感病毒血凝素(HA)来的“不加区别的”T细胞表位，恶性疟疟原虫红细胞前期抗原和分枝杆菌蛋白被报道能激发广泛的免疫应答。为了不加区别地结合于几种同型和同种异型的MHCⅡ类分子，这些肽类应显示出部重叠MHC结合形式或应利用保存于配体中的固定位点和应缺失等位基因特异性固定残基，以防止结合于其它Ⅱ类分子。了解MHCⅡ类分子对肽链的不加区别及特异性识别的生物物理学基础将为在疫苗设计中突破遗传限制的策略提供分子水平的依据。     

游离和前列腺特异性抗原相互关系及临床应用

目的　评价总前列腺特异性抗原 (tPSA)、游离前列腺特异性抗原 (fPSA)及百分率 (f/tPSA % )检测前列腺癌 (PCa)的相关性及临床价值。方法　用酶免法测定 35例PCa及 73例良性前列腺增生 (BPH)患者血清tPSA水平 ,4tPSA <10ng/ml患者另测其fPSA ,计算f/tPSA(% )。 结果　血清tPSA <4、4～ 10、>10ng/ml者发现PCa的比例组间相比均有统计学意义。 4～ 10ng/ml组 ,PCa和BPH者f/tPSA(% )分别是 9.1± 4.8、16 .4± 6 .1,差别有显著意义 (P <0 .0 1)。结论　tPSA仍是PCa筛查的有效瘤标 ,tPSA低水平时 ,f/tPSA(% )检测PCa则更为灵敏精确。     

Decreased hyperthermic effect of MK-801 in selectively bred hypercholinergic rats

The Flinders Sensitive Line (FSL) of rats has been selectively bred to have increased sensitivity to cholinergic agonists. However, these rats exhibit altered responsiveness to a number of noncholinergic agents, such as apomorphine, buspirone and ethanol. This study compared the FSL and control Flinders Resistant Line (FRL) rats in terms of their hyperthermic response to the phencyclidine (PCP) receptor agonist, MK-801 (0.2 mg/kg SC) and their MK-801 binding characteristics. We have found that FSL rats react with a delayed hyperthermia, having a significantly lower hyperthermia for the first 120 min of observation. Thereafter the response does not differ in FSL and FRL rats. Both groups had similar affinities and numbers of [3H]MK-801 binding sites in the hippocampus/cerebral cortex. Pretreatment with scopolamine (1 mg/kg SC) failed to affect MK-801-induced hyperthermia in either line of rats. These findings suggest that selective breeding of FSL rats attenuated the secondary mechanisms involved in the PCP receptor-mediated hyperthermic response. However, by itself cholinergic supersensitivity does not appear to be a major factor in the blunted responsiveness of FSL rats to MK-801.     

以病人选择医生为契机 全力推进人事分配制度改革

介绍了邯郸市中心医院在病人选医生中,努力完善制度,提高素质,深化内容,并以此为突破口,建立了灵活、高效的人事分配制度.用较为低廉的医疗费用,为人民群众提供了较好的医疗服务.     

反义人端粒酶RNA组分基因对胃癌细胞端粒酶活性的影响

目的 克隆人胃癌细胞端粒酶RNA组分（hTR）基因片段并构建其正义和反义真核表达载体,研究反义端粒酶RNA对人胃癌细胞株MKN-45端粒酶活性的影响。方法 采用RT-PCH方法从人胃癌细胞株MKN-45中扩增出人hTR部分cDNA序列,将该片段分别正向和反向插入PEF6/V5-His-TOPO载体后构建人端粒酶RNA组分（hTR）基因正、反义真核表达载体,随后采用脂质体转染法将该正、反义载体转染入人胃癌细胞株MKN-45,用TRAP法观察后者端粒酶活性的改变。结果 所克隆的基因片段其碱基序列与文献报导完全一致,且插入载体的方向完全正确。与正常对照、转染正义载体、空载体者比较,转染反义载体者端粒酶活性显著下降。结论 本实验已成功克隆了人端粒酶RNA组分（hTR）基因的部分序列并成功构建hTR正反义真核表达载体,而且反义端粒酶RNA能有效降低人胃癌细胞株MKN-45端粒酶活性。     

Prophylactic human papillomavirus vaccines: the beginning of the end of cervical cancer

Persistent infection with one of the oncogenic human papillomavirus (HPV) types is a necessity for the development of cervical cancer. By HPV vaccination, cervical cancer could become a very rare disease. Two types of HPV vaccines can be distinguished: (i) therapeutic vaccines which induce cellular immunity targeted against epithelial cells infected with HPV and (ii) prophylactic vaccines inducing virus-neutralizing antibodies protecting against new but not against established infections. At present, several vaccines have been developed and tested in clinical trials. The vaccines are generally well tolerated and highly immunogenic. The current clinical data indicate that prophylactic vaccines are very effective against new persistent infections and the development of cervical intraepithelial lesions. The protection is type specific. However, the follow-up of the vaccination trials is still short. The effect of HPV vaccines on future cancer incidence will only be known after decades of follow-up. This article will address the status of recently terminated phase II and currently running phase III trials with prophylactic HPV vaccines.     

Presence of beta human papillomaviruses in nonmelanoma skin cancer from organ transplant recipients and immunocompetent patients in the West of Scotland

Background  Nonmelanoma skin cancer (NMSC) has been linked to cutaneous human papillomaviruses of the genus beta (betaPV).
Objectives  We sought to assess the presence of betaPV in NMSC biopsies from a group of Scottish skin cancer patients, both immunocompetent (IC) patients and immunosuppressed (IS) organ transplant recipients.
Methods  One hundred and twenty-one paraffin-embedded skin tumours (27 actinic keratosis, 41 intraepidermal carcinoma, 53 squamous cell carcinoma) and 11 normal skin samples were analysed for the presence of betaPV by a polymerase chain reaction–reverse hybridization assay designed to detect the presence of the 25 known betaPV genotypes.
Results  In IC patients, betaPV was detected in 30 of 59 (51%) tumours and two of 11 (18%) normal skin samples ( P  =   0·046). In IS patients, betaPV was found in 27 of 62 (44%) tumours; no normal skin samples were available for comparison. The most frequently found genotypes were HPV-24, HPV-15 and HPV-38. Of those tumours infected with betaPV, 28 of 57 (49%) were infected with more than one genotype (range 2–8). Tumours from IS patients were from a younger age group (mean age 57·4 years) than IC patients (mean age 73·8 years). Multiple infections were more common in tumours from IC patients (21 of 30; 70%) compared with those from IS patients (seven of 27; 26%) ( P  <   0·001). In the IC group, age did not appear to influence the distribution of single and multiple infections whereas in IS patients the proportion of multiple infections to single infections increased with age. There were no multiple infections in normal skin.
Conclusions  A wide spectrum of betaPV types was detected in our samples. Further characterization of betaPV in vivo is needed in order to determine the mechanisms by which the virus contributes to cutaneous carcinogenesis.     

Lipid extract from completely sporoderm‐broken germinating Ganoderma sinensis spores elicits potent antitumor immune responses in human macrophages

Ganoderma sinensis has been used widely in Oriental countries for the prevention and treatment of various diseases including cancer. Previous studies have shown that the lipid extract from Ganoderma exhibits direct cytotoxicity against tumor cells. Here, it is reported that the lipid extract from germinating G. sinensis spores, at lower concentrations that have no direct tumoricidal activity, induce potent antitumor immune responses in human monocytes/macrophages. Upon stimulation with the lipid extract, monocytes/macrophages exhibited markedly increased production of proinflammatory cytokines and surface expression of costimulatory molecules. Conditioned medium from stimulated cells effectively suppressed the growth of tumor cells. Apparently, the lipid extract triggered macrophage activation via a mechanism different from that associated with LPS. Moreover, it was observed that the lipid extract could partially re‐establish the antitumor activity of the immunosuppressive tumor‐associated macrophages. These results indicated that in addition to its direct tumoricidal activity, the lipid extract from G. sinensis spores could exert antitumor activity by stimulating the activation of human monocytes/macrophages. Copyright © 2008 John Wiley & Sons, Ltd.     

聚合酶链反应检测患儿尿标本中的巨细胞病毒DNA

本文建立了聚合酶链反应(PCR)检测人巨细胞病毒(HCMV)方法,探讨了该方法的某些实验条件。用PCR检测24例临床患儿尿标本。证明PCR方法特异、敏感、简便而快速。同科不同属病毒如HSV、EBV等以及人源正常细胞均无假阳性结果:最小检出量可达0.1fg DNA,相当于6个基因拷贝;用水浴箱手控时间即可进行PCR循环,30次循环仅需97min30s;PCR和DNA杂交检测尿标本中HCMV阳性例数分别为20和14例。该结果证明HCMV感染儿童的广泛性和严重性,初步表明儿童肾病综合症与HCMV有关。     

加强行业管理规范人体器官移植技术

人体器官移植技术历经近半个世纪的发展历程．在上个世纪70年代我国逐步开展对肝脏、心脏和肾脏等器官移植技术的研究工作。近5年来，随着国际医学研究交流频繁，国内一些大型医疗机构加大了对器官移植技术上的投入．使人体器官移植技术发展迅猛。但同时也伴随着一些医疗费用过高、买卖供体等问题的出现。因此，如何规范人体器官移植技术．是当前的一个重要研究课题。