雌激素激活血管eNOS的机制

大量临床和基础研究证实雌激素具有显著的心血管保护效应，且该效应至少部分是通过增加血管内皮型一氧化氮合酶（eNOS）的表达和活性进而释放NO产生的。雌激素既可通过基因效应调节eNOS的表达，也可通过位于内皮细胞质膜微囊（caveolae）的ERα的一个亚群介导的非基因效应调节eNOS的活性。非基因效应与MAPK，PI3K/Akt等信号通路及内皮细胞质膜微囊密切相关，雌激素也可直接通过调节微囊蛋白-1表达而对eNOS的激活起负性调节作用。     

NF-κB与肺疾病

ＮＦκＢ是一种多极性基因调控蛋白，能调节多种参与炎症免疫反应的细胞因子、炎症介质、粘附分子及蛋白酶类的基因转录过程，从而控制它们的生物合成。哮喘和成人呼吸窘迫综合征（ＡＲＤＳ）是由多种细胞因子、炎性介质介导的免疫损伤性疾病，ＮＦκＢ能从基因转录水平调控肿瘤坏死因子α、白介素１β、白介素８、诱生型一氧化氮合酶、磷脂酶Ａ２等几种主要炎性细胞因子和介质的合成，因而在哮喘和ＡＲＤＳ的病理生理过程中具有重要的调节作用     

内皮型一氧化氮合酶基因多态性与临床疾病

内皮型一氧化氮合酶（eNOS)催化生成的一氧化氮（NO）具有舒张血管、抑制血管平滑肌细胞增殖、抑制血小板和白细胞粘附等功能，因此eNOS基因多态性可能与心血管等疾病的发生发展密切相关。     

组织特异性转录调控序列及在肿瘤基因治疗研究中的应用

肿瘤特征性蛋白“持家基因”转录调控序列是肿瘤细胞内特异活化的基因调控序列，可使外源基因在肿瘤细胞中特征性地表达。本文综述了普通启动子及组织特异性启动子的基本结构与功能，转录调控因子对启动子的调节以及目前在肿瘤基因治疗研究领域中应用价值的人酪氨酸酶（Tyr）启动子，甲胎蛋白（AFP）启动子，癌胚抗原（CEA）启动子等的研究进展。     

lncRNA-TUG1靶向Zeste同源物增强子2对缺氧心肌细胞的影响

目的：体外探讨长链非编码RNA(lncRNA)牛磺酸上调基因1(TUG1)靶向Zeste同源物增强子2(EZH2)对缺氧心肌细胞的影响。方法：缺氧诱导HL-1细胞建立细胞损伤模型，构建沉默质粒（siTUG1）和阴性对照（siNC）并分别转染至HL-1细胞内，随机分成常氧（normoxia）组、低氧（hypoxia）组、hypoxia+siNC组和hypoxia+si-TUG1组。采用RT-qPCR检测lncRNA-TUG1在各模型组中的表达。通过CCK-8分析细胞活力。ELISA检测心肌损伤标志物和炎症因子水平。RT-qPCR检测线粒体生物合成相关转录调节基因和炎症因子的表达。Western blot检测线粒体生物合成相关转录调节蛋白的表达。通过染色质沉淀（ChIP）检测lncRNA-TUG1、EZH2、内皮型一氧化氮合酶（eNOS）和脑源性神经营养因子（BDNF）间的互作关系。结果：与normoxia组相比，hypoxia组和hypoxia+siNC组细胞的活力、线粒体生物合成相关转录调节基因的表达均显著降低（P<0.05），而心肌损伤标志物和炎症因子水平均显著升高（P<...     

人GM-CSF基因调控及其功能研究进展

人粒细胞巨噬细胞集落刺激因子（ｈＧＭ－ＣＳＦ）在调节机体的重要功能中有重要作用，其基因表达受一系列正、负调控元件及多种转录因子的调控，它的５’侧翼区及３’侧翼区对其表达有重要作用。基因的表达水平受转录及转录后调控，且显示有组织特异性。     

内皮细胞应力反应元件的研究进展

内皮细胞能对力学刺激发生反应,流体切应力能直接调节内皮细胞基因的表达,现已发现内皮细胞内受切应力调节的基因有20多种。目前认为其调节机制是通过存在于基因的启动子内并且能够被切应力所诱导的启动基因转录的顺式调控元件－－应力反应元件来调节基因的转录。目前已知的应力反应元件至少涉及4种转录因子的结合位点及10余种受切应力调控的相关基因。这4种转录因子分别是：（1）NF－κB;（2）AP－1;（3）Egr-1和（4）SP1。对应力反应元件的基序及基序结合蛋白的鉴定有待进一步的深入,以后还可能有效的应力反应元件被发现。在采用基因疗法来调控血管壁不同区段基因表达这方面已进行了有益的探索,显示出良好的前景。     

一氧化氮及其信号转导通路在糖尿病性勃起功能障碍的作用

勃起功能障碍（erectile dysfunction,ED）是糖尿病的常见并发症,影响人们的生活质量,其病变机理还不甚清楚.一氧化氮（NO）由一氧化氮合酶（NOS）合成,是调节海绵体肌肉松弛和阴茎勃起的重要的神经递质.PI3-kinase/Akt （PKB）通路使eNOS磷酸化,NO的产量增加;NO/cGMPPKG通路参与平滑肌的舒张;RhoA和Rho-kinase参与平滑肌的收缩,抑制eNOS基因表达和酶的活性.周围血管病变和自主神经变性是引起糖尿病性ED的主要原因之一.基因和干细胞（eNOS、 RhoA/Rho-kinase与Mesenchymal stem cell-based cell）治疗糖尿病性ED取得一些进展.     

组织特异性转录调控序列及在肿瘤基因治疗研究中的应用

肿瘤特征性蛋白“持家基因”转录调控序列是肿瘤细胞内特异活化的基因调控离列，可使外源基因在肿瘤细胞中特征性地表达。本文综述了普通启动子及组织特异性启动子的基本结构与洋调控因子对启动子的调节以及目前在肿瘤基因治疗研究领域中的应用价值的人酪氨酸酶（Ｔｙｒ）启动了，甲胎蛋白（ＡＦＰ）启动子，癌胚抗原（ＣＥＡ）启动子等的研究进展。     

人类血管内皮细胞一氧化氮合成酶基因启动子序列的功能分析

目的 血管内皮细胞一氧化氮合成酶（ｅｎｄｏｔｈｉｌｉａｌ ｎｉｔｒｉｃ ｏｘｉｄｅ ｓｙｎｔｈａｓｅ,ｅｃＮＯＳ）在体内催化一氧化氮合成。为研究一氧化氮合成酶基因转录的调控,对一氧化氮合成酶基因启动子序列进行功能分析。方法 以血管内皮细胞核提取物为材料,采用凝胶迁移实验和ＤＮａｓｅⅠ足迹法实验。结果 启动子序列有３个区域与蛋白／转录因子结合。其中（－１０６～－８８）ＧＣ含量丰富,为转录因子ＳＰ１所     

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.     

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.     

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.     

The universal muscular chain reaction,muscle spasm,Torsions, ruptures and extravasations. Chameleons of pathology and some manifestations of simple muscular disorders

Most bodily functions require the coordinated actions of complementary and supplementary paired muscle groups. Where this essential muscular cooperation is lacking, hollow organs may burst and others become literally screwed up, giving rise to many similar spastic diseases such as Torticollis, Twisted ovarian cyst, Torsion of the Testis, Volvulus of the intestines, Varicose Veins, Megacolon, Aortamegaly, Scoliosis, Erb's Palsy, Peyronie's Disease, Main-en-Griffe, Undescended Foot (Pes Cavus), Talipes, Strabismus. Spasm is “panenepidemic” and unclassified examples of Torsion Dystonia and Dyskinesia really are as common as debt and taxes.     

Class II HLA in Georgia Caucasus Tbilisi Georgians and their Mediterranean ancestry: The Usko Mediterranean languages

Georgia (or Sakartvelo in its own language) is a South Caucasus Mts. country with its easternmost part is enigmatically named Iberia, like the Iberian Peninsula, which may refer to rivers “Kura” and “Ebro” or their valleys respectively. Most of their inhabitants speak Georgian which is included within Dene-Caucasian group and Usko-Mediterranean subgroup of languages. The latter includes Basque, Berber, ancient Iberian-Tartessian, Etruscan, Hittite, Minoan Lineal A and others. In the present paper, HLA class II -DRB1 and -DQB1 alleles has been studied and extended haplotypes calculated. Most frequent haplotypes are also of Mediterranean origin (i. e.: (A*02-B*51)-DRB1*11:01-DQB1*03:01, (A*02-B*51)-DRB1*13:01-DQB1*06:03, or (A*24-B*35)-DRB1*01:01-DQB1*05:01) and DA genetic distances show that closest world populations to Georgians are Mediterraneans. Georgians also show common extended haplotypes ((A*02-B*51)-DRB1*11:01-DQB1*03:01, (A*02-B*13)-DRB1*07:01-DQB1*02:01 and (A*03-B*35)-DRB1*11:01-DQB1*03:01) with Svan people, a secluded population in North Georgia mountains. We can conclude that Georgians belong to a very old Mediterranean substratum according to both linguistics (Usko Mediterranean languages) and HLA genetics.     

'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.     

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.