Twist基因蛋白表达在甲状腺乳头状癌诊断与鉴别诊断中的意义

目的探讨Twist基因蛋白在甲状腺乳头状癌中的表达状况,寻找更特异的标记物,用于甲状腺乳头状癌（PTC）与滤泡状腺瘤（FA）和良性乳头病变（BPL）的鉴别诊断。方法以50例PTC为研究组,以48例FA和47例BPL作对照组。在自制组织芯片上行免疫组织化学（SP法）标记,检测Twist基因蛋白和HBME-1,并以CK19进行对照。结果3种指标（Twist、HBME-1、CK19）阳性表达率：在PTC组分别为100％（48／48）、94．0％（47／50）和78．0％（39／50）;在FA组分别为0、6．7％（3／45）和0;在BPL组分别为7．0％（3／43）、2．1％（1／47）和0。PTC组分别与FA和BPL组比较差异均有统计学意义（P=0．000）。3种指标在鉴别诊断甲状腺良、恶性病变的灵敏度分别为：100％、96．4％和97．7％,特异度分别为：94．0％、95．7％和95．1％,准确度分别为：78．0％、100％和91．9％。结论Twist可应用于辅助诊断PTC,并可应用在对FA或BPL的鉴别诊断。     

甲状腺乳头状癌细针穿刺吸取细胞学中TROP-2表达及其临床意义

目的 探讨甲状腺乳头状癌(papillary thyroid carcinoma, PTC)细针穿刺吸取细胞学中TROP-2的表达及其临床意义。方法 收集86例PTC和19例良性甲状腺结节(benign thyroid nodules, BTN)临床资料，采用免疫组化法检测TROP-2的表达，并与常规标志物Galectin-3、HBME-1、CK19进行比较，分析TROP-2在甲状腺细胞学中诊断PTC的价值及其与PTC淋巴结转移的关系。结果 86例PTC组中TROP-2、Galectin-3、HBME-1、CK19阳性率分别为95.3%、82.6%、81.4%、90.7%,在BTN中仅个别表达，差异有统计学意义(P<0.05);结果显示TROP-2阳性率最高，且灵敏度、特异性、阳性预测值、阴性预测值及准确度均高于Galectin-3、HBME-1、CK19。TROP-2、Galectin-3、HBME-1、CK19诊断PTC的AUC分别为0.950、0.886、0.828、0.848,结果显示TROP-2对于诊断PTC效能最高；PTC细胞学中TROP-2表达与淋巴结转移呈正相关(...     

甲状腺乳头状癌中CK19、Galectin-3、HBME-1和TPO的表达及意义

目的 探讨CK19、Galectin-3、HBME-1和TPO在甲状腺良恶性病变中的表达及联合应用在甲状腺乳头状癌鉴别诊断中的价值.方法 采用免疫组化EnVision法检测68例甲状腺乳头状癌、31例甲状腺腺瘤、19例结节性甲状腺肿和15例桥本甲状腺炎中CK19、Galectin-3、HBME-1和TPO的表达.结果 在甲状腺乳头状癌中CK19、Galectin-3和HBME-1的阳性表达率分别为98.5%、98.5%、80.9%,TPO的阴性表达率为89.7%;在甲状腺良性病变中CK19、Galectin-3和HBME-1阳性表达率分别是24.6%、21.5%、1.5%,TPO的阴性表达率是1.5%.CK19、Galectin-3、HBME-1和TPO在甲状腺乳头状癌与良性病变中的表达差异有显著性(P<0.001).联合应用四种抗体在鉴别甲状腺乳头状癌与良性病变时的敏感性、特异性、准确度分别为95.6%、98.5%、97%.结论 CK19、Galectin-3、HBME-1和TPO是诊断甲状腺乳头状癌的重要标志物.联合应用四种抗体在甲状腺乳头状癌与良性病变的鉴别诊断中具有重要价值.     

细胞角蛋白19、galectin-3、HBME-1在甲状腺病变上的表达及鉴别诊断意义

目的 研究细胞角蛋白(CK)19、galectin(Gal)-3、HBME-1在甲状腺不同病变表达的特点及鉴别诊断中的应用价值。方法 应用免疫组织化学EnVision法检测了21例结节性甲状腺肿(结甲)、14例毒性甲状腺肿(甲亢)、15例甲状腺滤泡性腺瘤(腺瘤)、13例滤泡性癌、13例滤泡型乳头状癌及48例经典型乳头状癌中单克隆抗体CK19、Gal-3、HBME-1的表达。结果 甲状腺病变中3种标记表达均位于细胞质;CK19、Gal-3、HBME-1的表达在甲状腺良性病变(结甲、甲亢、腺瘤)大多为弱阳性或阴性,而滤泡性癌阳性明显增加、乳头状癌(滤泡型及经典型)大多为中、强阳性,3种标记在甲状腺不同病变的阳性表达率结甲为52．4％(11／21)、9．5％(2／21)、19．0％(4／21),甲亢为50．0％(7／14)、7．1％(1／14)、7．1％(1／14),腺瘤为60％(9／15)、13．3％(2／15)、13．3％(2／15),滤泡性癌为76．9％(10／13)、61．5％(8／13)、53．8％(7／13),滤泡型乳头状癌为：100％(13／13)、84．6％(11／13)、92．3％(12／13),经典型乳头状癌为100％(48／48)、93．8％(45／48)、95．8％(46／48);在甲状腺良性病变(结甲、甲亢、腺瘤)与恶性病变(滤泡性癌、乳头状癌)间3种标记差异均有显著性(P均=0．000);同时3种标记在滤泡样病变即腺瘤、滤泡性癌和滤泡型乳头状癌间亦有显著差异(CK19：P=0．038,Gal-3：P=0．001,HBME-1：P=0．000)。结甲有9例,甲亢有7例,腺瘤有6例3种标记均不表达,滤泡性癌仅有1例,而乳头状癌(滤泡型及经典型)没有病例3种标记均不表达,同一病例有2种以上阳性表达在结甲、甲亢、腺瘤、滤泡性癌、滤泡型乳头状癌和经典型乳头状癌中分别为14．2％(3／21)、21．4％(3／14)、20．0％(3／15)、69．2％(9／13)、92．3％(12／13)、100．0%(48／48),在甲状腺良性病变与恶性病变间以及滤泡样病变间差异亦有显著性(P=0．000)。结论 CK19、Gal-3、HBME-1的检测尤其是联合检测对甲状腺病变的诊断、鉴别诊断具有较高的实用价值。     

甲状腺乳头状癌术中冷冻切片诊断及延迟原因分析

目的探讨甲状腺乳头状癌(papillary thyroid carcinoma,PTC)的临床病理特征、诊断及鉴别诊断。方法收集165例PTC的病理资料,光镜下观察术中冷冻切片及常规石蜡切片,并对其中12例行免疫组化染色,检测CK19、Galectin-3、MC、CK (34βE12)、CD56及Ki-67的表达,同时行BRAF基因突变检测。结果 165例患者中女性134例,男性31例,经术中冷冻诊断确诊141例,准确率为85. 5%。延迟诊断21例(12. 7%),假阴性诊断3例(1. 8%)。CK19和Galectin-3在PTC中呈强阳性。BRAF基因V600E突变7例。结论 PTC女性多见,术中冷冻切片对PTC的诊断具有重要应用价值,病理医师需掌握冷冻切片中组织结构及细胞形态的变异,以提高诊断的准确性。CK19和Galectin-3有助于PTC的诊断,BRAF基因突变检测可作为临床评估患者预后的重要参考指标。     

甲状腺乳头状癌RET、CK19、TG、Ki-67的表达

目的 研究甲状腺乳头状癌RET、CK19、TG、Ki-67蛋白表达特点及其临床意义。方法 应用免疫组织化学SP法检测RET、CK19、TG、Ki-67蛋白在30例甲状腺乳头状癌、10例结节性甲状腺肿和18例癌旁正常甲状腺中的表达。结果 RET、CK19在乳头状癌的阳性率（66．7％、83．3％）明显高于结节性甲状腺肿和正常甲状腺阳性率（7．1％、25．0％）,两者差异有显著性（P〈0．01）。乳头状癌组及良性病例组TG表达阳性率差异无显著性（P〉0．05）。96．7％的乳头状癌Ki-67阳性细胞数小于10％。结论 RET及CK19在甲状腺乳头状癌表达增加,具有一定的病理诊断价值。     

Galectin-3和CD44v6在甲状腺癌中的表达及临床价值

为观察Galectin-3和CD44v6在甲状腺良、恶性结节中的表达差异,探讨其在甲状腺癌鉴别诊断中的临床价值,应用免疫组化方法检测30份甲状腺癌组织、38份甲状腺良性结节及29份正常甲状腺组织中Galectin-3和CD44v6的表达。结果显示,甲状腺癌组织中Galectin-3和CD44v6的阳性率均显著高于良性结节和正常甲状腺组织（P〈0．005）,其中乳头状癌和滤泡状腺癌的阳性率显著高于其它类型癌组织（P〈0．005）。结论：Galectin-3和CD44v6可以作为甲状腺癌鉴别诊断的较有价值的标志物。     

甲状腺微小乳头状癌中Galectin-3、CK19、HBME-1和CD56的表达及意义

目的探讨结节性甲状腺肿合并甲状腺微小乳头状癌中Galectin-3、CK19、HBME-1及CD56的表达及意义。方法采用免疫组化SP法检测10例结节性甲状腺肿合并甲状腺微小乳头状癌中Galectin-3、CK19、HBME-1和CD56的表达水平。结果 Galectin-3、CK19和HBME-1在甲状腺微小乳头状癌中均呈中至强阳性表达,而在结节性甲状腺肿中主要呈阴性或弱阳性表达。然而在10例甲状腺微小乳头状癌中有8例CD56的表达均为阴性,2例呈轻度阳性着色;周围结节性甲状腺肿组织9例均呈中至强阳性表达,仅1例呈轻度阳性着色。结论 Galectin-3、CK19、HBME-1及CD56联合检测将进一步提高甲状腺微小乳头状癌的准确性。     

桥本甲状腺炎伴不典型细胞与乳头状癌的鉴别诊断

目的：探讨桥本甲状腺炎伴不典型细胞与甲状腺乳头状癌( papillary thyroid carcinoma,PTC)的鉴别诊断。方法收集桥本甲状腺炎153例,分为桥本甲状腺炎伴不典型细胞组(32例)、桥本甲状腺炎伴PTC组(49例)、桥本甲状腺炎对照组(72例)。采用HE及免疫组化法分析各组间的差异。结果桥本甲状腺炎伴不典型细胞与PTC有形态学差异。伴PTC组Galec-tin-3、CK19阳性率高于伴不典型细胞组,CD56阳性率低于伴不典型细胞组,差异均有统计学意义。 Ki-67阳性率在伴不典型细胞组与伴PTC组之间差异无显著性,但与对照组之间差异有统计学意义。结论以组织形态学特征为基础,联合应用CD56、CK19、Galectin-3、Ki-67可有效鉴别桥本甲状腺炎伴不典型细胞与PTC。     

巨滤泡型甲状腺乳头状癌3例并文献复习

目的探讨巨滤泡型甲状腺乳头状癌(papillary thyroid carcinoma,PTC)的临床病理特点和形态学特征。方法采用免疫组化En Vision两步法检测3例巨滤泡型PTC,观察其组织学形态,并复习相关文献探讨其诊断和鉴别诊断。结果巨滤泡型PTC主要由大滤泡构成,内含浓稠胶质,细胞呈半透明,细胞呈矮柱状或立方状。免疫组化标记癌组织中CK19、HBME-1均呈弥漫强阳性,Galectin-3有1例呈中等程度阳性,其余2例呈弥漫强阳性。CD56均呈阴性。结论巨滤泡型PTC形态学特殊,临床病理诊断易误诊为结节性甲状腺肿或滤泡型腺瘤等良性病变,联合免疫组化检测有助于其诊断。     

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.