整合素αv、α4在小鼠胚泡植入中的作用

目的：探讨整合素αv、α4在小鼠胚泡植入中的作用。方法：在体外培养的人蜕膜细胞中分别加入整合素αv、α4抗体，与小鼠胚泡共培养，观察整合素αv、α4抗体对小鼠胚泡在体外培养的人蜕膜细胞上的粘附和铺展的影响。结果：整合素αv抗体组，胚泡的粘附受到暂时抑制，48h时大部分胚泡才粘附并开始铺展；整合素α4抗体组，胚泡的粘附率不受影响，但铺展率及滋养层细胞的扩展面积以剂量依赖的方式受到抑制。结论：整合素αv、α4能够调节胚泡在人蜕膜细胞上的植入，其中整合素αv可能与胚泡的粘附有关，而整合素α4可能与胚泡侵入和滋养层细胞的进一步生长相关。     

食管癌细胞表面DR5的表达分布与细胞铺展状态的关系

目的：探讨食管癌鳞癌EC9706细胞系细胞表面DR5的表达分布与细胞铺展状态的关系。方法：免疫细胞化学技术分析食管癌EC9706细胞的DR5表达分布；流式细胞术检测食管癌细胞表面DR5的表达及细胞的凋亡率。结果：DR5分布在食管癌EC9706细胞的细胞质和细胞膜表面，主要在细胞质，但在细胞核没有DR5分布，而且在悬浮的食管癌细胞表面DR5表达高于铺展者。悬浮的食管癌细胞对抗DR5功能性抗体诱导的细胞凋亡敏感性高于铺展者。结论：食管癌细胞表面DR5的表达与细胞铺展状态具有密切的关系，细胞铺展状态的变化直接影响细胞表面DR5的表达分布以及对抗DR5功能性抗体诱导的细胞凋亡敏感性。该研究结果对进一步探讨DR5表达分布的机制以及TRAIL和DR5的功能性抗体的抗肿瘤临床应用有一定的指导意义。     

不同基底硬度对人肝癌细胞黏附、铺展和迁移的影响

目的研究不同基底硬度对肝癌细胞黏附、铺展和迁移行为的影响及对细胞骨架装配方式和细胞表面黏附蛋白整合素β1表达的调控,探讨基底的力学特性在肝癌细胞恶性转移过程中的作用。方法通过调节丙聚酰胺和双丙烯酰胺的比率制备不同硬度的聚丙烯酰胺基底,并在基底表面裱衬2.5μg/mL纤维连接蛋白为细胞提供黏附位点;用显微观察并记录不同硬度基底上细胞黏附、铺展和迁移的变化,并用Image J软件定量分析;分别运用免疫荧光和流式细胞仪的方法检测不同基底硬度对肝癌细胞骨架装配和细胞表面整合素β1表达的影响。结果硬基底利于肝癌细胞的黏附和铺展并缩短细胞的铺展时间。过软(1.1 kPa)或过硬(玻璃)的基底都不利于肝癌细胞的迁移,肝癌细胞在中间硬度的基底上(10.7 kPa)迁移速率最高。硬基底促进细胞骨架的装配和整合素β1表达。结论基底硬度通过调节细胞骨架装配和整合素的表达从而影响肝癌细胞的黏附、铺展和迁移。     

联会复合体的硝酸银染色技术

联会复合体是减数分裂前期Ⅰ出现的一种核内非永久性细胞器,与同源染色体联会、交换、重组、分离有着密切的关系,早期研究联会复合体是通过减数分裂前期细胞连续超薄切片进行三维重组。这种方法费时费力,观察细胞数目有限,不仅不能用光镜观察,而且在一张超薄切片上不可能观察到一条完整的联会复合体,更谈不上一整套联会复合体。Counce和Meyer首次用微铺展技术,成功地把蝗虫初级精母细胞的一整套联会复合体铺展在载玻片上,运用磷钨酸染色方法在电镜下看到了联会复合体的三层结构[1]。1977年,     

微模式化基底上大鼠骨髓间充质干细胞的增殖、分化和迁移

目的　利用微模式化基底研究基底几何微结构对骨髓间充质干细胞增殖、分化及迁移过程的影响。方法　设计制作微模式化基底,用以控制细胞的铺展形态和面积。比较不同模式控制下大鼠骨髓间充质干细胞的增殖、分化和迁移数据。结果　细胞铺展宽度狭小可抑制骨髓间充质干细胞的增殖,细胞铺展形状可以调节其向成骨细胞分化的进程,细胞铺展面积受限时迁移增强,其增殖迁移行为减弱与成骨细胞诱导因子地塞米松的作用有关。结论　细胞铺展的几何形状和面积是骨髓间充质干细胞增殖、分化及迁移过程中的重要调节因子。     

甲基丙烯酸环氧丙酯诱导人胚肺细胞恶性转化相关基因片段的克隆

本研究在建立GMA诱导的HELF体外恶性转化模型的基础上，采用mRNA差异显示（DD－PCR）技术，对恶性转化细胞同正常细胞之间基因的差异表达状况进行了比较分析，共克隆到18个差异表达cDNA片段，其中，17个DNA片段与已知基因高度同源，另外一个为新基因序列。Northern杂交证实，分别有8个和3个基因在GMA诱导的恶性转化细胞中表达增加或降低，结果提示，这些基因可能参与了GMA诱导的细胞恶性转化过程，为进一步研究GMA诱导细胞转化及其潜在致癌机理提供了新的线索。     

基于琼脂糖/壳聚糖共混凝胶模型的壳聚糖生物相容性的机理研究

目的 以琼脂糖/壳聚糖共混凝胶为模型,研究壳聚糖材料生物相容性的可能机理.方法 通过共混法,制备出一系列不同壳聚糖含量的琼脂糖/壳聚糖共混凝胶.利用傅里叶变换红外光谱(FTIR)分析共混凝胶的化学基团,利用荧光素-4-异硫氰酸酯(FITC)标记法观察琼脂糖和壳聚糖之间的可共混性.通过Zeta电势测量共混凝胶的电荷,利用二喹啉甲酸(BCA)法分别测定胎牛血清(FBS)总蛋白和牛血清白蛋白(RSA)在共混凝胶上的吸附,利用酶联免疫吸附(ELISA)法测定纤黏连蛋白(FN)在共混凝胶上的吸附.细胞实验以人微血管内皮细胞系(HMEC-1)为模型,通过观测细胞的黏附、增殖和形态来评价共混凝胶的细胞相容性.结果 琼脂糖/壳聚糖共混凝胶含有壳聚糖特征性的化学基团.琼脂糖和壳聚糖之间存在着良好的可共混性,壳聚糖的氨基基团在共混凝胶中呈均匀分布.在pH酸性条件下(pH 3.0)共混凝胶带有较强的正电荷,然而在pH中性条件下(pH 7.4)所有共混凝胶的Zeta电势均降低至0 mV附近.各组共混凝胶之间对FBS总蛋白以及BSA的吸附差异无统计学意义,但是共混凝胶对FN的吸附却随着壳聚糖含量的升高而显著升高.细胞实验结果显示:随着壳聚糖含量的提高,共混凝胶的细胞相容性有明显改善,HMECs在壳聚糖含量较高的凝胶上表现出良好的黏附、铺展和增殖.结论 相对于血清中的其他蛋白,壳聚糖组分对FN存在优先吸附,从而能够促进细胞在共混凝胶表面的黏附铺展.与传统观点不同,本研究发现壳聚糖的生物相容性与其所携带的正电荷无关.     

人参总皂甙诱导人造血基质细胞表达IL-3的实验研究

目的 研究人参总皂甙(TSPG)对人早期血细胞发生的影响及其机理，进一步探讨人参“补气生血”的现代分子生物学机理。方法 采用造血祖细胞体外培养、造血生长因子(HGF)生物活性检测、免疫细胞化学、核酸分子原位杂交技术，研究TSPG对造血基质细胞表达白细胞介素-3(IL-3)的影响及其机理。结果 TSPG体外作用能明显促进人早期髓系多向性造血祖细胞(CFu-Mix)的集落形成；经TSPG诱导制备的人骨髓基质细胞(BMSG)、脐静脉内皮细胞株(EcV304)、单核细胞株(THP)条件培养液对CFU-Mix的增殖分化有明显促进作用；经TSPG诱导后BMSC、EcV304、THP细胞内IL-3的蛋白及mRNA表达显著提高。结论 TSPG能促进人早期血细胞的增殖分化，其机理可能与TSPG诱导人造血基质细胞表达IL-3有密切关系。     

异种供体移植物与受体体内抗供体抗体共存机理的初探

为探索大鼠→兔异种造血嵌合体模型中， 大鼠造血细胞与受体兔抗大鼠单个核细胞抗体长期共存的机理， 作者通过直接、间接免疫荧光染色技术及补体介导的细胞毒试验等方法， 发现嵌合体中大鼠 Ｍ Ｈ ＣⅠ类分子阳性细胞比例为３１０ ％ ～６１９ ％ ， 但能结合兔抗大鼠 Ｉｇ Ｇ 的细胞比例仅为２０ ％ ～７９ ％ 。表明大多数大鼠单个核细胞表面未结合兔抗大鼠单个核细胞抗体。据此， 提出大鼠细胞表面的某些抗原“缺失”的见解， 但 “缺失” 的抗原中不包括 Ｍ Ｈ ＣⅠ类分子， 且这些抗原的“缺失”不影响大鼠细胞的体液免疫功能。在此基础上进一步讨论了 Ｍ Ｈ Ｃ 分子在异种移植中的作用和分子“丢失” 与异种移植耐受产生的关系。     

缺血性细胞人务体外培养模型的建立

为了建立简便有效的缺血性损伤实验模型，利用无（低）葡萄糖培养基培养ＳＫ－Ｎ－ＳＨ细胞系，再用包括细胞活率测定、光学显微镜观察、电镜检测、荧光染色、流式细胞仪检测等多种细胞生物学方法，分析和研究包括凋亡等在内的动物缺血性模型及患者缺血组织中常见的细胞开矿及功能的改变，建立了简便的有利进一步研究缺血性损伤的细胞体外培养模型。     

Renal dysplasia and asplenia in two sibs

A family is reported in which two sibs, one male and the other female, both died within 24 hours of birth with enlarged polycystic kidneys. Postmortem histology in the second child showed gross renal dysplasia. In both children the pancreas was enlarged, nodular and cystic but the liver appeared macroscopically normal. In the second child, histological examination confirmed pancreatic fibrosis with cystic dilation of ducts, but showed portal fibrosis with bile duct proliferation in the liver.
This combination of findings is very reminiscent of those in a girl and her brother reported by Ivemark et al. (1959). The children reported here also showed absence or hypoplasia of the spleen, cardiac anomalies and other features of the Ivemark syndrome (Ivemark 1955), a quite different, usually sporadic, congenital disorder. It is suggested that the children described here have a distinct lethal congenital disorder, probably inherited in an autosomal recessive manner.     

Schizophrenia in a North Swedish geographical isolate, 1900–1977. Epidemiology, genetics and biochemistry

Over 200 schizophrenic patients belonging to three major and interrelated pedigree complexes have been investigated over the past 30 years in a North Swedish geographically isolated population, presently numbering about 6,000. An intensive investigation of a number of biochemical correlates and genetic markers in a few selected families belonging to one of the major pedigrees has indicated new strategies for the current research program.
Schizophrenia, as defined operationally, is significantly associated with decreased activities of two enzymes (1) blood platelet monoamine oxidase, (2) plasma dopamine-β-hydroxylase, and (3) with the genetic marker Gc² (group specific antigen). Both enzymes are subject to genetic variation. A positive score for linkage between schizophrenia and low plasma DBH activity has been calculated, but, so far, available data are insufficient for discrimination between linkage and partial contribution of genetically controlled low plasma DBH to the pathogenesis of the disease. Alternatively, both mechanisms could be involved.
As a model for continued research, schizophrenia is explained as based on a double dominant-recessive genotype (Aabb), representing a vulnerability which in about 50 % of cases develops into clinical schizophrenia. It is suggested that the dominant mutation (A) operates on or affects MAO activity, and that the recessive genotype (bb) is instrumental in low variates of DBH activity and very likely such variates within the normal range of physiological variation. Moreover, it is suggested that the combined effects of MAO- and DBH-reduced efficiency on the metabolism of e.g. dopamine could be an essential pathogenic mechanism for the schizophrenic illness which is segregating in this population.     

The dominant diseases of modernized societies as omega-3 essential fatty acid deficiency syndrome: Substrate beriberi

About 1900, modern food selection and processing caused widespread $\text{epidemics}$ of the B vitamin deficiency diseases of beriberi and pellagra which, for genetic reasons, often expressed as different diseases ranging from bowel and heart disease to dermatoses and psychoses. But the B vitamins merely help convert essential fatty acids (EFA) into the prostaglandin (PG) tissue regulators and it now turns out that, through hydrogenation, milling and selection of w3-poor southern foods, we have also been systematically depleting, by as much as 90%, a newly discovered trace Nordic EFA (w3) of special importance to primates and sole precursor of the PG3(4) series, even as a concurrent fiber deficiency increases body demand for EFA. Since substrate EFA is processed by many B vitamin catalysts, an EFA deficiency will mimic a $\text{panh}$ypovitaminosis B, i.e., a mixture of $\text{substrate}$ beriberi and $\text{substrate}$ pellagra resembling vitamin beriberi and pellagra but exhibiting as even more diverse $\text{endemic}$ disease. This would consitute a second stage of the Modern Malnutrition and explain why some workers now hold the dominant diseases of modermized societies to be new, nutritionally based, pellagraform yet lipid-related and to range, once again, from heart disease to psychosis. It is an assumption that our dominant diseases are unrelated to each other or are merely revealed by our diagnostic acumen and therapeutic success; and that hydrogenating millions of tons of food oils annually, to destroy the rancidity producing w3-EFA, is safe for $\text{primates}$. Extensive beriberiform disease is reported here in 32 typical cases taken from medical practice which responds strikingly to linseed oil supplements (60% w3-EFA) in confirmation of identical results in Capuchins.     

What will studies of Fulani individuals naturally exposed to malaria teach us about protective immunity to malaria?

There are an estimated over 200 million yearly cases of malaria worldwide. Despite concerted international effort to combat the disease, it still causes approximately half a million deaths every year, the majority of which are young children with Plasmodium falciparum infection in sub-Saharan Africa. Successes are largely attributed to malaria prevention strategies, such as insecticide-treated mosquito nets and indoor spraying, as well as improved access to existing treatments. One important hurdle to new approaches for the treatment and prevention of malaria is our limited understanding of the biology of Plasmodium infection and its complex interaction with the immune system of its human host. Therefore, the elimination of malaria in Africa not only relies on existing tools to reduce malaria burden, but also requires fundamental research to develop innovative approaches. Here, we summarize our discoveries from investigations of ethnic groups of West Africa who have different susceptibility to malaria.     

'Very sore nights and days': the child's experience of illness in early modern England, c.1580-1720

Sick children were ubiquitous in early modern England, and yet they have received very little attention from historians. Taking the elusive perspective of the child, this article explores the physical, emotional, and spiritual experience of illness in England between approximately 1580 and 1720. What was it like being ill and suffering pain? How did the young respond emotionally to the anticipation of death? It is argued that children’s experiences were characterised by profound ambivalence: illness could be terrifying and distressing, but also a source of emotional and spiritual fulfilment and joy. This interpretation challenges the common assumption amongst medical historians that the experiences of early modern patients were utterly miserable. It also sheds light on children’s emotional feelings for their parents, a subject often overlooked in the historiography of childhood. The primary sources used in this article include diaries, autobiographies, letters, the biographies of pious children, printed possession cases, doctors’ casebooks, and theological treatises concerning the afterlife.     

Guidelines for the Validation and Use of Immunoassays for Determination of Introduced Proteins in Biotechnology Enhanced Crops and Derived Food Ingredients

Recent advancements in agricultural biotechnology have created a need for analytical techniques to determine introduced proteins in crops enhanced through modern biotechnology techniques. These proteins are expressed in plant tissues and may be present in food ingredients. Immunoassays are ideally suited for protein detection and may be used as both quantitative and threshold methods. Microplate ELISA and lateral flow devices are two of the most commonly used immunoassay formats for agricultural biotechnology applications. This paper provides general background information and a discussion of criteria for the validation and application of immunochemical methods to the analysis of proteins introduced into plants and food ingredients using biotechnology methods. It is the result of a collaborative effort of members of the Analytical Environmental Immunochemical Consortium. This collaborative effort represents the combined expertise of several organizations to reach consensus on establishing guidelines for the validation and use of immunoassays. Further, the paper offers developers and users a consistent approach to adopting the technology as well as aid in producing accurate and meaningful results.     

HLA in North Colombia Chimila Amerindians

HLA-A,-B,-C,-DRB1 and -DQB1 alleles have been studied in Chimila Amerindians from Sabana de San Angel (North Colombian Coast) by using high resolution molecular typing. A frequent extended haplotype was found:HLA-A*24:02-B*51:10-C*15:02-BRB1*04:07-DQB1*03:02 (28.7%) which has also been described in Amerinndian Mayos Mexican population (Mexico, California Gulf, Pacific Ocean). Other haplotypes had already been found in Amerindians from Mexico (Pacific and Atlantic Coast), Peru (highlands and Amazon Basin), Bolivia and North USA. A geographic pattern according to HLA allele or haplotype frequencies is lacking in Amerindians, as already known. Also, five new extended haplotypes were found in Chimila Amerindians. Their HLA-A*24:02 high frequencies characteristic is shared with aboriginal populations of Taiwan; also, HLA-C*01:02 high frequencies are found in New Zealand Maoris, New Caledonians and Kimberly Aborigines from Australia. Finally, this study may show a model of evolutionary factors acting and rising one HLA allele frequency (-A*24:02), but not in others that belong to the same or different HLA loci.     

Ultracryotomy: development and application (with examples from the yeast cytology) (author's transl)

The preparation steps usually necessary for obtaining ultrathin frozen sections of biological material (chemical prefixation, enclosing, cryoprotective treatment, freezing, sectioning, and post-staining the sections for transmission electron microscopy) are submitted to a critical analysis. The application of cryo-ultramicrotomy, in particularly for cytochemical purposes, is reviewed. Fundamental considerations of chemical prefixation and poststaining are supported by examples from yeast cytology. Furthermore, the efficiency of the cryo-ultramicrotomy (electron optical resolution of ultrastructural details) is demonstrated on yeast cells and protoplasts.     

The universal muscular chamber. A basic unit of the genitourinary, cardiovascular, gastro-intestinal, skeletal, cutaneous, respiratory and other systems, endocameral hypertension; and spasm, the key to their idiopathic diseases and arthropathies

Starting with the integument, we see many organs are contractile sacs or multiples thereof, which tubes or bags constitute the major part of the entire body. Recognition of this basic unit and its characteristics sheds new light, individually and collectively, on many disorders previously considered unrelated. Muscular tears and perforations develop in the walls of these chambers, being no way peculiar to those organs, wherein, hydrochloric acid occurs. So, it is not necessary to explain the absence of excessive acid from patients who exhibit holes in the gastric, uterine, aortic, duodenal, rectal, pulmonary, retina, and other walls. Muscle, not acid is the great common factor relating idiopathic disorders in the gastrointestinal tract to each other and to similar diseases in other systems. When the units are linked together, the lesions tend to appear as arthropathies, i.e. at the joints. Rephrasing common-place observations, frees us from conventional, conceptual cul-de-sacs. An observation is only as good as its interpretation, so all possibilities must be considered, otherwise, we will remain blinded by our misconceptions.