维吾尔族女性乳腺增生性病变与癌变组织中Notch1基因甲基化的差异比较

目的比较维吾尔族女性乳腺导管增生性病变和导管癌变组织中Notch1基因甲基化的差异情况。方法应用MALDITOF MS定位和定量检测Notch1基因在维吾尔族乳腺普通型导管增生(usual ductal hyperplasia,UDH)、非典型性导管增生(atypical ductal hyperplasia,ADH)、导管原位癌(ductal carcinoma in situ,DCIS)、浸润性导管癌(invasive ductal carcinoma,IDC)中甲基化率的变化,分析其与临床病理特征的关系,采用免疫组化法检测Notch1蛋白表达并分析其与甲基化的关系。结果Notch1基因在UDH、ADH、DCIS、IDC的甲基化率逐渐降低(P0.05),13个Cp G位点中9个位点甲基化率明显下降(P0.05),其低甲基化率伴随着低分化、淋巴结转移和TNM高分期(P0.05),Notch1基因低甲基化率与Notch1蛋白表达呈负相关(P0.05)。结论 Notch1蛋白表达和甲基化率在乳腺导管的不同增生性病变及乳腺癌变组织中存在一定的差异,其生物学意义有待进一步研究。     

乳腺导管内增生性病变中ER、Ki-67和cyclin D1的表达

目的 探讨ER、Ki-67和cyclin D1在乳腺导管内增生性病变中的表达及意义。方法 采用免疫组化和免疫荧光双标记法对56例乳腺导管内增生性病变进行ER、 Ki-67和cyclin D1染色标记。结果 正常乳腺组织中仅有散在的少数上皮细胞呈ER阳性表达。在普通型导管增生（usual ductal hyperplasia，UDH）中ER表达比正常乳腺组织增加，但ER阳性细胞呈不连续分布，阳性细胞间有较多的阴性细胞。非典型性导管增生（atypical ductal hyperplasia，ADH）和低级别原位导管癌（ductal carcinoma in situ，DCIS）中ER表达比UDH明显增加（P〈0．05），ER阳性细胞呈连续的片状分布，阳性细胞间较少或没有ER阴性细胞。ADH和低级别DCIS中ER表达较高级DCIS显著（P〈0．01）。DCIS中Ki-67和cyclin D1表达高于UDH（P〈0．05），并与UDH、ADH和DCIS的组织学分组呈正相关（r=0．352，P〈0．05和r=0．390，P〈0．05）。正常乳腺组织中上皮细胞内无ER和Ki-67同时表达。在UDH中有极少数上皮细胞ER和Ki-67同时表达，而在ADH和DCIS中ER和 Ki-67同时表达的细胞明显增加。结论 从正常乳腺组织到UDH、ADH、低级DCIS的恶性转化过程中伴有ER表达的逐渐增高。ER过度表达及ER和Ki-67在上皮细胞内同时表达可能是某些乳腺癌发生过程中的早期事件。     

乳腺导管内增生性病变是乳腺癌前驱病变

乳腺导管内增生性病变是一组发生于终末导管小叶单位且限定于乳腺导管小叶系统的增生性病变,表现为细胞形态多样性和组织结构多样性,包括普通型导管增生(usual ductal hyperplasia, UDH)、不典型导管增生(atypical ductal hyperplasia, ADH)、不典型平坦上皮增生(flat epithelial atypia, FEA)和导管原位癌(ductal carcinoma in situ, DCIS).     

交界性导管增生性乳腺病的病理诊断

导管增生性乳腺病包括一组谱系性病变，即导管上皮普通型增生(usual ductal hyperplasia，UDH)、非典型增生(a-typical ductal hyperplasia，ADH)和导管原位癌(ductal car-cinoma in situ，DCIS)。增生谱系中的中-重度UDH、ADH和低核级DCIS是鉴别诊断的难点。许多乳腺病理学家致力于确定有助于鉴别上述交界性疾病的组织学特征。Page     

散发性乳腺癌和乳腺增生细胞8p、16q微卫星DNA位点的杂合性缺失

目的研究散发性乳腺癌细胞和乳腺增生细胞中位于8p和16q的3个微卫星DNA(microsatellite,MS)位点D8S264、D8S258、D16S413的杂合性缺失(loss of heterozygosity,LOH)的频率;探索3个MS的LOH频率同乳腺癌淋巴结转移状态的关系。方法分离乳腺癌和乳腺增生病理切片上的病变细胞和正常对照细胞并分别提取DNA,采用PCR-变性PAGE电泳检测18例单纯增生(usual hyperplasia,UH)、15例不典型增生(atypical hyperplasia,AH)以及35例浸润性乳腺导管癌(invasive ductalcarcinoma,IDC)细胞中位于8p的D8S264、D8S258和位于16q的D16S413位点的LOH频率。结果 UH、AH、IDC组发生D8S264、D8S258和D16S413的LOH频率分别为7.1%、0、0,18.2%、11.1%、20%和42.8%、32%、34.7%,除D16S413外,IDC组的D8S264和D8S258的LOH频率明显高于UH组和AH组(P0.05);UH、AH、IDC组3个MS位点总LOH频率分别为5.6%、40%、57.1%,UH组与其余两组的差异有统计学意义(P0.05),AH与IDC组差异无统计学意义(P0.05);淋巴结转移阳性组和阴性组D8S264、D8S258、D16413的LOH频率及总LOH频率分别为36.4%、28.6%、42.9%、55.6%和47.1%、33.3%、31.7%、58.3%,组间的差异均无统计学意义(P0.05)。结论 IDC组频繁发生D8S264、D8S258、D16413的LOH,UH和AH组也发生了不同程度的LOH,其中发生于UH组的D8S264以及较高频率发生于AH组的D16S413值得关注和进一步研究;AH组与IDC组的3个MS位点总LOH频率较接近;D8S264、D8S258、D16413的LOH与淋巴结转移状态无关。     

基底型细胞角蛋白在乳腺导管内增生性病变诊断中的应用

目的比较不同类型基底型细胞角蛋白(CK5、CK34βE12和CK14)在乳腺导管内增生性病变中的辅助诊断价值,并结合肌上皮标记、超微电镜对普通型导管增生的细胞成分进行初步分析。方法参照2003年WHO乳腺疾病分类的诊断标准筛选出28例导管普通型增生(UDH)、10例不典型增生(ADH)和25例导管原位癌(DCIS)。所有病例均进行CK5/6、CK34βE12、CK14、CK8、浕SMA、calponin和p63的免疫组化染色。4例UDH和1例DCIS通过电镜观察其增生细胞的超微结构。结果CK5/6在UDH、ADH和DCIS增生细胞中的阳性表达率分别为92.9%、10.0%和0。CK34βE12和CK14的阳性表达率分别为96.4%和82.1%(UDH)、20.0%和30.0%(ADH)、24.0%和28.0%(DCIS)。所有UDH的增生细胞均不表达浕SMA、calponin和p63。电镜观察显示UDH和DCIS的增生细胞中未发现符合肌上皮超微特征的细胞存在。结论基底型CK有助于UDH和ADH/DCIS的鉴别诊断,其中CK5/6较CK34βE12和CK14特异性更高。免疫组化染色和电镜观察结果支持UDH的增生细胞含有多种成分,包括定向干细胞、腺中间细胞和腺终端细胞等,但未发现具有肌上皮特点的细胞参与其中。     

头颈部鳞癌的微卫星不稳定性和杂合性丢失的初步研究

目的:探讨头颈部鳞癌的微卫星不稳定性(MSI)及杂合性丢失(LOH)。方法:选择来自3、5、6、8、9、13、17和18号染色体的15个微卫星标志对36例头颈部鳞癌标本和相应的外周血进行微卫星分析。结果:36例头颈部鳞癌中,27.8%(10/36)分别有1-8个位点存在MSI,MSI发生率较高的位点为:D17S520(22.9%)、D6S105(16.7%)和D8S264(13.9%)。在9p21-p22和3p14等处存在一定的LOH。微卫星异常的检出率与肿瘤分期、分级无相关性。结论:提示MSI是头颈部鳞癌中较为常见的遗传学变化,染色体9p21-p22和3p14区域可能存在与头颈部鳞癌有关的抑癌基因。     

肝细胞癌8号染色体微卫星变异及其与临床病理特征的关系

目的　探讨肝细胞癌 (HCC)微卫星变异的特点及其与临床病理表现的相关性。方法采用毛细管电泳DNA分析系统 ,对 5 6例HCC中 8号染色体上 10个微卫星的杂合子丢失 (LOH)、微卫星不稳定性 (MSI)和等位基因失衡 (AI) 3种变异特征进行检测。结果　 5 6例HCC在 8号染色体上 10个基因位点发生LOH的总频率为 6 6 1% (37/ 5 6 ) ,LOH以D8S2 6 1最高为 5 3 5 % (2 3/ 4 3) ,其次为D8S172 1(5 2 5 % )和D8S1771(5 2 5 % )。D8S2 77基因位点 ,血清HBsAg阳性患者的LOH频率显著高于HBsAg阴性者 (P <0 0 1) ,D8S2 6 1、D8S2 98和D8S1733基因位点 ,血清HBsAg阴性患者的LOH频率显著高于HBsAg阳性者 (P <0 0 1) ;D8S2 98和D8S1771基因位点 ,直径 >3cm肿瘤的LOH率明显高于≤ 3cm组 (P <0 0 5和P <0 0 1) ;在D8S172 1基因位点 ,无包膜或包膜不完整的肿瘤的LOH显著高于包膜完整的肿瘤 (P <0 0 1) ;D8S2 98和D8S1771基因位点 ,肝内转移者的LOH明显高于无肝内转移者 (P <0 0 5 )。MSI的频率为 12 5 % (7/ 5 6 ) ,AI的频率为 19 6 % (11/ 5 6 )。结论HCC在 8号染色体上存在广泛的微卫星变异 ,其中LOH方式在HCC的发生和发展过程中起重要作用 ,MSI的作用次之。特定基因位点的LOH与临床和病理学参数有一定的相关性     

乳腺癌和乳腺导管内增生性病变Notch1基因甲基化的检测及临床意义

目的 探讨Notch1基因甲基化与乳腺浸润性导管癌(IDC)及乳腺导管内增生性病变的相关性.方法 用基质辅助激光解析电离时间飞行质谱仪(MALDI-TOF MS)对89例乳腺IDC、20例导管原位癌(DCLS)、11例不典型导管增生(ADH)及20例普通型导管增生(UDH)组织进行Notch1基因甲基化的定量检测.采用...     

鼻咽癌染色体1pter-p36.11杂合性缺失

目的构建鼻咽癌染色体1pter-p36.11(63.4cM)区域内的杂合性缺失精细图谱,为进一步寻找鼻咽癌相关基因提供依据。方法在比较基因组杂交和间期荧光原位杂交研究基础上,应用淋巴分离液将肿瘤组织的肿瘤细胞与淋巴细胞分离并以淋巴细胞DNA作相应正常对照,利用1pter-p36.11区域内的20个微卫星多态位点(平均间距3cM)对47例鼻咽癌活检组织用杂合性缺失(LOH)分析法进行LOH分析并绘制其精细缺失图谱。结果在47例鼻咽癌患者中,至少有一个位点存在LOH的有37例(82.2%),其中LOH频率最高的为D1S234(50.0%),位于1p36.13,其次为D1S2644(37.5%),位于1p36.22;微卫星不稳定频率最高的为D1S243(37.5%),位于1p36.33,其次为D1S199(30.2%),位于1p36.21;D1S234的LOH及D1S199的MI与临床分期相关无显著性意义（P>0.05）。结论鼻咽癌染色体1pter-p36.11之间63.4cM区域内有两个共同的缺失区,分别位于1p36.13(D1S234,2.0cM)与1p36.22(D1S436-D1S2644,6.3cM),其间有一个微卫星不稳定位点D1S199,D1S436-D1S199-D1S234区域内可能有一个或几个在早期与鼻咽癌形成相关的肿瘤抑制基因。     

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.