雌激素受体α、β亚型在子宫平滑肌瘤中的表达特征

目的：探讨雌激素受体(ER)α、β亚型的表达量在子宫平滑肌瘤发病中的意义。方法：取自愿手术的子宫肌瘤患者30例为研究对象,应用非放射性原位杂交技术方法测定平滑肌瘤组织中ER和ERβmRNA的表达,并与正常的平滑肌组织相比较。结果：ERαmRNA和ERβmRNA主要在平滑肌细胞中表达。子宫肌瘤和正常的平滑肌组织中ERαmRNA的表达量高于ERβmRNA;ERαmRNA在子宫肌瘤中的表达明显高于正常的平滑肌组织,而ERβmRNA的表达仅呈下降趋势。结论：子宫肌瘤的发生发展可能与ERαmRNA的高表达有关,亦可能与ERβmRNA减少趋势有关。     

ERα和ERβ在正常子宫内膜、异常增生子宫内膜和子宫内膜癌组织中的表达及意义

目的探讨雌激素受体（ER）亚型α和β mRNA及蛋白的异常表达与子宫内膜癌的发生发展的关系。方法应用半定量逆转录聚合酶链反应（RT—PCR）和免疫组织化学链霉菌抗生物素蛋白-过氧化酶连接法（SP法）,检测18例正常子宫内膜组织、29例异常增生组织和50例子宫内膜癌组织中ERα、ERβ mRNA及蛋白的表达。结果①ERα mRNA在内膜癌组织中的阳性表达率和阳性表达水平明显低于异常增生内膜组织及正常内膜组织,三者比较有显著性差异（P〈0．01）,ERα蛋白在这三组间的表达率变化相同（P〈0．05）。②ERβ mRNA在内膜癌组织中的阳性表达率和阳性表达水平明显低于增生性内膜组织及正常内膜组织,三者比较有显著性差异（P〈0．01）,ERβ蛋白在这三组间的表达率变化相同（P〈0．01）。③ERα和ERβ mRNA平均表达水平比值（ERα／ERβ）在内膜癌组低于异常增生子宫内膜组织和正常子宫内膜组（P〈0．05）。结论ERα和ERβ表达的下调可能与子宫内膜癌的发生有关,在这个过程中ERα的下调起的作用大于ERβ。     

子宫平滑肌瘤中TRIP6蛋白及mRNA的表达

目的 探讨甲状腺激素受体相互作用蛋白6(thyroid receptor-interacting protein 6, TRIP6)在子宫平滑肌瘤中的表达及临床靶向药物治疗中的意义。方法 采用Western blot法检测子宫平滑肌瘤和瘤旁正常子宫平滑肌组织中TRIP6蛋白表达，应用RT-PCR检测子宫平滑肌瘤和瘤旁正常子宫平滑肌组织中TRIP6 mRNA表达。结果 11例子宫平滑肌瘤组织中，有8例(8/11,72.72%)TRIP6蛋白表达低于正常子宫平滑肌组织(P<0.05);有7例(7/11,63.64%)TRIP6 mRNA表达显著低于正常子宫平滑肌组织(P<0.05);其中，有7例(7/11,63.64%)TRIP6蛋白与mRNA表达水平一致降低。结论 TRIP6在子宫平滑肌瘤中的表达降低，提示TRIP6表达降低可能与子宫平滑肌瘤的发生、发展相关。     

雌激素受体基因多态性与妇科疾病关系研究进展

雌激素受体（ER）是雌激素的结合位点，是信号转导的始发站。研究表明，人ER有α和β两种亚型，由不同的基因编码，两者均存在多种遗传多态性，从而可能影响ERα和ERβ的表达和功能，因此与许多雌激素相关性疾病的发生和发展有着密切关联。目前国内外研究较多的是乳腺癌、子宫内膜异住症、子宫肌瘤等疾病与ER基因多态性的关系。本文就ER结构、ER基因常见遗传多态性及其与女性六种疾病（子宫内膜异位症、子宫肌瘤、子宫内膜癌、绝经后骨质疏松、原因不明月经过少及复发性流产）相关性的研究进展进行综述。     

女性压力性尿失禁与雌激素受体β同分异构体的相关性分析

目的研究女性尿道支撑组织成纤维细胞中雌激素受体β(ERβ)同分异构体的表达,从而获得雌激素受体β同分异构体在女性压力性尿失禁中的作用及机制。方法取阴道前壁组织作为研究标本,并取正常对照组标本及患者实验组标本各5例。体外构建女性尿道支撑组织成纤维细胞模型。用免疫组织化学、RT-PCR、ELISA以及Western blot等方法检测尿道支撑组织中ERβ及ERβ同分异构体的表达水平。结果免疫组化检测的结果发现,与对照组相比,实验组的ERβ表达存在一定程度的下调。Western blot的结果显示,实验组中的ERβ蛋白含量明显低于正常组组织中的ERβ蛋白含量。用RT-PCR方法检测ERβ各个亚型表达之后发现,与对照组相比,实验组的ERβ1、ERβ2、ERβ3、ERβ5 mRNA均下调表达。结论雌激素受体β同分异构体的表达下调与女性压力性尿失禁的发病相关联。     

ERα、ERβ、pS2蛋白在子宫平滑肌肉瘤组织中的表达及意义

目的研究ERα、ERβ、pS2蛋白在子宫平滑肌肉瘤组织中的表达及意义。方法选取1997年1月~2004年5月间,青岛大学医学院,青岛市第三人民医院,第八人民医院,收治的子宫肌瘤和平滑肌肉瘤患者128例的石蜡块,用免疫组化法测定ERα、ERβ、pS2表达。结果子宫平滑肌肉瘤中,ERα阳性率(36.1%),子宫肌瘤中ERα阳性率(83.6%),两者比较有显著性差异(P<0.01);其强度亦有显著性差异(P<0.01);平滑肌肉瘤ERβ阳性率(18.0%)子宫肌瘤中ERβ阳性率(59.7%),两者比较有显著性差异(P<0.01);其强度亦有显著性差异(P<0.01)。平滑肌肉瘤pS2阳性率(41.0%)子宫肌瘤pS2率(23.9%),两者比较有显著性差异(P<0.05);pS2在子宫平滑肌肉瘤中的表达强度比在子宫肌瘤中高,两者比较有显著性差异(P<0.05)。随着子宫肉瘤临床分期的增加,ERα、pS2的阳性表达率降低,差异有显著性(P<0.05);ERα、ERβ、pS2在绝经前比在绝经后高,各指标在绝经前后比较都有显著性差异P<0.01。结论ERα、ERβ、pS2与子宫平滑肌肉瘤的发病机制有关,与子宫平滑肌肉瘤的预后有关。     

前列腺组织中ERα、ERβ的表达及其意义

目的探讨雌激素及其受体ERα、ERβ与良性前列腺增生(benign prostatic hyperplasia,BPH)、前列腺癌(prostate cancer,PCa)的关系。方法采用免疫组化SP法检测ERα和ERβ在20例正常前列腺(normal prostate,NP)、80例BPH及46例PCa标本中的表达。结果 ERα主要在前列腺组织间质细胞表达,上皮细胞中无表达,在NP中呈低表达,在BPH中高表达,而在PCa表达下降(P0.01);但ERα在PCa不同病理分级和临床分期中的表达强度差异无显著性(P0.05)。ERβ主要在前列腺组织上皮细胞表达,很少位于间质,在NP、BPH中高表达,而在PCa中表达下降甚至呈阴性(P0.01),ERβ表达与分化程度呈正相关(P0.01),且主要表达于A、B期组织中(P0.01)。结论 ERα主要在间质细胞表达,而ERβ主要在上皮细胞表达,提示雌激素对BPH及PCa的作用可能主要是通过ERβ途径发挥作用的。ERβ在PCa中的表达明显下降,提示其可能与PCa的发生、发展有关,推测PCa中大部分ERβ可能是更具有侵袭性的ERβ变异体,致使PCa恶性程度增加。     

绝经妇女外周血单个核细胞骨代谢调控因子表达变化

目的:探讨绝经妇女雌激素水平下降所致免疫细胞骨代谢调控因子变化。方法:纳入绝经妇女、未绝经妇女各30例,电化学发光法检测血清雌二醇(E2)水平;RT-PCR法检测外周血单个核细胞(PBMC)中雌激素受体(ERα、ERβ)、白细胞IL-6、TNFα-。核因子κB受体活化因子配基(RANKL)、核因子κB受体活化因子(RANK)mRNA表达;ELISA检测血清IL-6、TNFα-蛋白含量;双能X线骨密度仪检测腰椎2~4(L2-4)前后位骨密度(BMD)。结果:与未绝经组比较,绝经妇女E2水平明显下降,腰椎BMD显著降低(P<0.05),外周血单个核细胞ERα、ERβmRNA表达明显降低(P<0.05),IL-6、TNFα-、RANKL、RANKmRNA表达明显升高(P<0.05),IL-6及TNFα-血清蛋白含量明显升高(P<0.05)。相关性分析显示PBMC中ERα、ERβmRNA表达与血清E2水平、腰椎BMD呈显著正相关性(P<0.05),PBMC中IL-6、TNFα-、RANKL、RANKmRNA表达与血清E2水平、腰椎BMD呈显著负相关性(P<0.05)。结论:绝经后妇女雌激素水平下降伴随着外周血免疫细胞雌激素受体转录水平下降,同时,炎性骨吸收调控因子和溶骨性细胞因子表达升高,这种变化可能在绝经后骨丢失中发挥重要作用。     

卵巢切除对大鼠子宫雌激素受体亚型表达的影响

目的 通过对去卵巢大鼠雌激素受体亚型在子宫表达的观察，研究卵巢切除对大鼠子宫影响的机制。方法 选择成年Wistar大鼠30只，10只为正常组，10只为假手术组，10只为模型组(去卵巢组)。6周后处死大鼠，分离摘取子宫，常规石蜡包埋、切片，分别进行ERα、ERβ抗体的免疫组织化学染色。结果 1．ERα在正常组、假手术组及模型组子宫的上皮细胞、间质细胞及肌细胞核均有表达，其中以腺上皮细胞表达最强。图像分析表明，模型组腺上皮ERα表达较其他2组弱。2．ERα在去卵巢子宫中未见明显表达，只在正常组和假手术组子宫腺上皮细胞核中表达，且较ERα表达弱。结论卵巢切除后明显影响大鼠子宫ERα、ERα的表达，尤其对ERα的影响较为显著。     

雌激素受体不同亚型在卵巢子宫内膜异位症在位内膜与异位内膜中的表达及其意义

目的 研究雌激素受体(ER)不同亚型在子宫内膜异位症的在位和异位内膜中的表达,以寻找其在不同病灶中的分布规律,探讨子宫内膜异位症的发病机制.方法 收集解放军总医院2004年1月-2006年12月行手术治疗的卵巢子宫内膜异位症石蜡标本,包括卵巢子宫内膜异位囊肿60例及其在位内膜60例(增生期各30例、分泌期各30例)以及正常子宫内膜30例(增生期和分泌期各15例).采用免疫组织化学(EnVision)方法检测上述组织中ERα和ERβ的表达.染色结果半定量化,并分析比较各种组织间的表达差异.结果 各组中,ERα和ERβ在腺上皮的表达与它们在间质细胞中的表达呈正相关.ERα蛋白在不同部位的表达:在位内膜ERα的表达(腺上皮和间质细胞阳性率分别为73.3%和76.7%)高于卵巢子宫内膜异位囊肿(腺上皮和问质细胞阳性率分别为43.4%和46.7%)和正常内膜的表达(腺上皮和间质细胞阳性率分别为56.7%和50.0%),均P<0.05.ERβ蛋白在不同部位的表达:卵巢子宫内膜异位囊肿(腺上皮和间质细胞阳性率分别为90.0%和76.7%)高于在位子宫内膜的表达(腺上皮和间质细胞阳性率分别为68.0%和63.3%),后者又高于正常子宫内膜(腺上皮和间质细胞阳性率分别为36.7%和26.7%),P均<0.05.在位内膜的ERα和ERβ蛋白表达在增殖期均高于分泌期,P均<0.05;异位内膜增殖期和分泌期的表达差异无统计学意义.ERα和ERβ蛋白在不同部位表达的比较:在正常内膜中ERα的表达略高于ERβ,但差异无统计学意义,P>0.05;卵巢子宫内膜异位囊肿中ERβ的表达高于ERα,P<0.05;而在位内膜中两种亚型表达差异无统计学意义.结论 子宫内膜异位症患者在位子宫内膜及异位内膜均有ERα和ERβ的表达,但与正常子宫内膜相比,在卵巢子宫内膜异位囊肿中ERβ表达占优势,而ERα表达受限.ERα和ERβ在不同组织中的分布及表达水平与子宫内膜异位症的发生和发展有着密切关系.     

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.