骨桥蛋白相关分子与肿瘤转移的关系

骨桥蛋白（OPN）及其相关分子与肿瘤转移的关系密切。通过转录因子与OPN启动子的应答元件（RAE序列、Tcf-4结合序列、AP-1结合序列、RE-1序列等）相互作用,调控OPN的表达。OPN通过促进肿瘤细胞黏附、激活生长因子受体、促进MMPs或uPA分泌、促进血管生成等多个环节参与肿瘤转移过程     

抗氧化剂与大肠癌细胞MMP-3表达关系研究

核因子-kB(nuclear factor kappa B,NF-κB) 是一种重要的细胞转录因子,参与多种细胞增殖、凋亡和癌基因等的转录调控.细胞核因子-kB通过上调与侵袭和转移有关的多个基因蛋白表达,从而参与肿瘤的侵袭和转移.因此,通过抑制NF-κB的活化,间接下调相关下游基因蛋白表达,从而抑制肿瘤的侵袭和转移正成为一种新的抗肿瘤治疗方法.本实验旨在探讨大肠癌MMP-3蛋白表达及NF-kB抑制剂二硫氨基甲酸吡啶PDTC(pyrrolidine dithiocarbamate)对大肠癌MMP-3蛋白表达的影响,为大肠癌转移的治疗提供新的理论依据.     

调控STAT3α和STAT3β信使RNA剪切的顺式作用元件的确定及其特征

ＮＦ κＢ参与肿瘤的生长与转移 ;ＳＴＡＴ3在肝病急性期的炎症反应中有重要作用。两者都定位于胞浆 ,接受信号刺激被激活并转移至核内 ,通过调控肿瘤生长、转移及炎症反应相关基因的表达 ,发挥效应 ,具有转录因子的作用。同时 ,ＮＳ5Ａ通过激活转录因子参与调控细胞内转录 ,但确切机制不明。本文旨在针对ＮＳ5Ａ作为转录因子的激活因子时的作用机制的研究。结果表明ＮＳ5Ａ可激活ＳＴＡＴ3和ＮＦ κＢ ,并使它们具有核转位能力。其机制是 :ＮＳ5Ａ粘附于内质网膜并介导内质网的应激 ,产生应激后内质网释放钙离子 ,后者被线粒体吸收使跨膜电…     

转录因子环腺苷酸反应元件结合蛋白在肿瘤转移中的作用及其分子机制

目的肿瘤转移是复杂而精细的有序过程,其机制包括细胞骨架纤维重排、上皮-间质化发生和microRNAs的调控等。环腺苷酸反应元件结合蛋白(CREB)作为细胞内重要的转录因子,通过自身磷酸化和过表达,改变细胞骨架纤维重排、上皮-间质化发生和与microRNAs的相互作用等,参与调控肿瘤转移。我们综述了近几年的研究成果,探讨CREB在肿瘤转移中的作用及分子机制,为以CREB为靶点的预防和治疗肿瘤转移奠定基础。     

缺氧诱导因子-1与细胞凋亡

缺氧诱导因子 1(HIF -1)是一种主要由缺氧诱导细胞产生的重要的转录因子。HIF- 1的表达水平与糖酵解、细胞周期阻滞、细胞生存与增殖、血管新生、血管舒缩、红细胞生成、肿瘤生长,转移以及肿瘤多药耐药等许多生命活动密切相关。HIF- 1通过调控凋亡相关基因的转录在促细胞凋亡和抗细胞凋亡中都发挥着重要的作用。     

乙型肝炎病毒X基因的转录激活作用及其机理的研究进展

乙型肝炎病毒X基因的翻译产物可在多种细胞中反式激活乙型肝炎病毒和其他数种病毒以及一些细胞基因的调控序列,促进基因转录。X蛋白的作用与病毒增强子的某些序列有关,可能通过细胞内转录调控因子桥接直接作用于转录起始复合物,或X蛋白本身具有蛋白磷酸激酶活性,共价修饰细胞转录调控因子,进而影响转录起始。X蛋白的反式激活作用有利于病毒基因的大量表达,促进病毒复制,并且可干扰细胞基因的转录表达,影响细胞分化增殖,是导致病毒大量复制和细胞肿瘤转化的重要因素之一。     

MTA1与肿瘤侵袭转移的研究进展

肿瘤转移相关基因 1(MTA1)是NuRD的亚单位之一,它通过促进组蛋白脱乙酰基,影响基因的转录和复制。研究发现,它与乳腺癌、食道癌、胃肠癌、胰腺癌等多种人类上皮源性肿瘤侵袭转移的能力紧密相关,它的高表达与肿瘤的侵袭深度与病理分级呈正相关,可作为评价预后的一个指标。     

PIG7基因与Litaf/Simple蛋白

PIG7基因是与p53诱导凋亡密切相关的基因,与代谢、炎症、肿瘤等关系紧密。该基因可能存在2种不同的转录本——Litaf与Simple,Litaf在LPS诱导TNF-α表达过程中起转录激活作用,Simple可能参与溶酶体介导的细胞内蛋白分选和降解过程。     

转录因子GATA2在TNF-α介导的炎症反应中调节Tie2基因的表达

目的：探讨在炎症刺激因子肿瘤坏死因子-α（TNF-α）介导的炎症反应中转录因子GATA家族成员是否参与了Tie2基因的转录调控。方法: 采用实时定量PCR测定TNF-α作用前后人主动脉内皮细胞（HAECs）和肺动脉内皮细胞（HPAECs）中GATA家族成员GATA2、GATA3 mRNA的表达,利用荧光素酶活性检测研究GATA转录因子能否激活Tie2基因启动子,并采用电泳迁移变动分析（EMSAs）和超级迁移率变动试验（supershift）研究GATA转录因子是否通过与Tie2基因启动子结合,从而激活Tie2基因的表达。结果: TNF-α可诱导人血管内皮细胞HAECs和HPAECs中转录因子GATA2的表达,高表达的GATA2可与Tie2基因启动子上的（T/A）GATA(A/G)序列结合,激活Tie2基因启动子,从而上调Tie2基因的表达。结论: GATA转录因子家族成员GATA2在TNF-α介导的炎症反应中调节了Tie2基因的表达。     

分化抑制因子及其与肿瘤性血管生成

分化抑制因子(Id)属于螺旋-环-螺旋(HLH)转录因子家族,缺乏DNA结合所必须的碱性氨基酸,在与bHLH结合形成二聚体后抑制bHLH与DNA及其他组织特异性bHLH转录因子结合,起负调节作用。哺乳动物Id有4种亚型,各种亚型的生物学功能各异。Id基因具有原癌基因特性,编码的Id蛋白能阻止细胞分化,促进细胞增殖,参与肿瘤的发生。Id基因在多种原发性肿瘤中均有表达,它是肿瘤性血管生成必需的,并与肿瘤的侵袭、转移有一定关系。     

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.     

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.     

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.     

'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.     

Der Einfluß von Nahrungsmitteln und Rauchen auf die klinisch-chemische Diagnostik von Phäochromozytom,Neuroblastom und Karzinoid-Syndrom

Zusammenfassung Der Einfluß von verschiedenen Nahrungsmitteln auf Methoden zur Bestimmung von Adrenalin (AD), Noradrenalin (NA), Vanillinmandelsäure (VMS), Metanephrinen (MN), Homovanillinsäure (HVS) und 5-Hydroxyindolessigsäure (5-HIE) im 24 h-Harn zur Diagnose des Phäochromozytoms bzw. Karzinoid-Syndroms wurde untersucht. Die in die Untersuchung einbezogenen Nahrungsmittel waren: Tee, Kaffee, Mandeln, Ananas, Käse, Walnüsse, Vanillepudding, Bananen, Tomaten und Milchschokolade. Außerdem wurde der Einfluß des Zigarettenrauchens auf die Bestimmung von AD, NA, VMS und MN untersucht.Walnüsse führten zu einer starken Erhöhung der 5-HIE-Ausscheidung. Bananen erhöhten die Ausscheidung von AD, NA, VMS, MN und 5-HIE. Kaffee und Ananas bewirkten eine geringe Zunahme der MN-Werte. Rauchen von 20–30 Zigaretten/Tag beeinflußte keine der vier Variablen.Wenn die beschriebenen Methoden benutzt werden, sollte lediglich auf den Verzehr von Bananen und Walnüssen vor und während der Harnsammelperioden verzichtet werden, da die oberen Normgrenzen im Harn überschritten werden könnten. Ein Verzicht auf Kaffee und Ananas in normalen Mengen ist nicht erforderlich. Es besteht kein Anlaß, weiterhin die bisherigen umfangreichen Restriktionen der übrigen Nahrungsmittel beizubehalten.