桥本甲状腺炎不典型细胞群Galectin-3、CK19、CK7的表达及意义

目的探讨桥本甲状腺炎(Hashimoto′s thyroiditis,HT)中不典型细胞群与甲状腺乳头状癌(papillary thyroid carcinoma,PTC)的关系及其临床病理意义。方法从存档病例中选取45例PTC和40例HT,以40例腺瘤周围甲状腺组织为对照,进行常规形态学观察和Gal-3、CK19和CK7、MaxVision法免疫组化染色,以χ2检验分析表达结果。结果(1)HT增生的淋巴滤泡周围可见到PTC-核样改变的不典型细胞群;(2)Gal-3在PTC,HT不典型细胞群及对照组表达率分别为89%,10%,0,差异有统计学意义(P<0.05),前组高于后两组,后两组间差异无统计学意义(P>0.05);(3)CK19和CK7在PTC,HT不典型细胞群及对照组的阳性表达率分别为100%,95%,10%和95%,92.5%,12.5%,两种抗体的阳性率和表达部位均较接近,前两组均高于对照组(P<0.05),PTC和HT两组间差异无统计学意义(P>0.05)。结论Gal-3在HT不典型细胞群和PTC组表达的差异性可协助诊断HT是否合并PTC;CK19和CK7在HT不典型细胞群中与PTC组有类似的表...     

涎腺腺样囊性癌和基底细胞腺瘤的免疫表型及临床病理特征

目的观察CK7、Calponin、CD117、Ki-67在涎腺腺样囊性癌(adenoid cystic carcinoma,ACC)和基底细胞腺瘤(basal celladenoma,BCA)中的免疫表型及其病理组织形态学差异,以提高对该类肿瘤鉴别诊断的认识。方法对发生于涎腺的26例BCA和17例ACC进行临床和病理组织形态观察并免疫组化标记(CK7、Calponin、CD117、Ki-67)。结果临床特点为两种肿瘤的发病年龄相似,但发生部位不同,ACC好发于腮腺以外的小涎腺,BCA多数发生于腮腺;病理特点为前者表现为浸润性生长并累及周围组织;免疫组化显示两种肿瘤存在免疫表型差异:其中CD117在ACC和BCA之间的强阳性率差异有统计学意义(P<0.05);Ki-67在BCA和ACC之间的强阳性率差异有统计学意义(P<0.01)。结论 ACC具有浸润性生长的生物学特征,病理特点上与BCA鉴别主要基于两者的生长方式和组织形态学检查,CD117和Ki-67免疫组化标记有助于其鉴别诊断。     

Clinicopathological characteristic and immuniohistochemical staining of the adenoid cystic carcinoma and basal cell adenoma in salivary gland

目的 观察CK7、Calponin、CD117、Ki-67在涎腺腺样囊性癌(adenoid cystic carcinoma,ACC)和基底细胞腺瘤(basal cell adenoma,BCA)中的免疫表型及其病理组织形态学差异,以提高对该类肿瘤鉴别诊断的认识.方法 对发生于涎腺的26例BCA和17例ACC进行临床和病理组织形态观察并免疫组化标记(CK7、Calponin、CD117、Ki-67).结果 临床特点为两种肿瘤的发病年龄相似,但发生部位不同,ACC好发于腮腺以外的小涎腺,BCA多数发生于腮腺;病理特点为前者表现为浸润性生长并累及周围组织;免疫组化显示两种肿瘤存在免疫表型差异:其中CD117在ACC和BCA之间的强阳性率差异有统计学意义(P<0.05);Ki-67在BCA和ACC之间的强阳性率差异有统计学意义(P<0.01).结论 ACC具有浸润性生长的生物学特征,病理特点上与BCA鉴别主要基于两者的生长方式和组织形态学检查,CD117和Ki-67免疫组化标记有助于其鉴别诊断.     

免疫组化检测Ki-67、 HER-2、 CD44、 CK20在膀胱非浸润性乳头状尿路上皮癌分级中的应用

目的探讨免疫组化检测Ki-67、HER-2、CD44、CK20在鉴别低级别和高级别非浸润性乳头状尿路上皮癌中的有效性。方法收集642例分级明确的乳头状尿路上皮癌及57例分级不确定的乳头状尿路上皮癌,根据有无高级别复发或进展,将分级不确定病例分为高危组及低危组,采用免疫组化EnVision法检测Ki-67、HER-2、CD44、CK20的表达。结果将Ki-67≥30%、HER-2全层表达、CD44表达减弱、CK20全层表达定义为阳性,分级明确病例中,低级别组Ki-67、HER-2、CD44、CK20的阳性率分别为12%、15%、28%、21%,高级别组分别为76%、70%、52%、67%,差异均有显著性(P0.001);分级不确定病例中,低危组Ki-67、HER-2、CD44、CK20的阳性率分别为40%、49%、28%、40%,高危组分别为70%、70%、20%、30%。结论免疫组化检测Ki-67、HER-2、CD44、CK20在低级别和高级别乳头状尿路上皮癌中的表达差异有显著性,可以用于乳头状尿路上皮癌分级的辅助诊断,其中Ki-67和HER-2在鉴别中有重要意义。     

CK19、COX-2、hTERT在桥本甲状腺炎合并甲状腺乳头状癌中的表达及意义

目的探讨桥本甲状腺炎(Hashimoto's thyroiditis,HT)与甲状腺乳头状癌(papillary thyroid carcinoma,PTC)的关系及HT癌变的可能机制。方法对HT和HT合并PTC,以及单纯PTC各30例,分别进行HE染色形态学观察,及CK19、COX-2、hTERT免疫组化染色。结果 HT病变区域与癌巢之间可见滤泡上皮细胞过度增生→非典型增生→乳头状癌的移行过渡现象。CK19、COX-2、hTERT在正常甲状腺组织中均未见表达,在HT、HT合并PTC及PTC中呈不同程度的阳性表达,与正常组相比差异有统计学意义(P0.05),同时在HT合并PTC组中,在相对正常的滤泡上皮细胞中阴性,非典型增生的滤泡上皮及乳头状癌组织中阳性表达(P0.05)。结论 HT和PTC关系密切,HT具有一定的恶变潜能。HT伴非典型增生性改变,可能是PTC的早期事件。COX-2和hTERT在HT合并PTC的发生、发展中起着重要作用。CK19可作为早期检测HT合并PTC的参考指标。     

CK19、TPO、CD56、p63标记在甲状腺良恶性乳头状增生诊断与鉴别诊断中价值

目的 探讨CK19、TPO、CD56及p63标记在甲状腺良恶性乳头状增生中的表达及其在诊断与鉴别诊断中的价值.方法 采用免疫组化SP法检测61例甲状腺乳头状癌(papillary thyroid carcinoma,PTC)与28例良性乳头状增生(benign papillary hyperplasia,BPH)中CK19、TPO、CD56及p63的表达.结果 CK19、TPO、CD56及p63在PTC中的阳性率分别是77%、9%、16%、21%,而其在BPH中的阳性率分别是11%、86%、68%、43%,四者在PTC与BPH中的阳性率差异有显著性(P<0.05).CK19、TPO、CD56及p63用于PTC诊断时的灵敏度分别是77%、9%、16%、21%,特异度分别是89%、14%、32%、57%,联合应用时灵敏度及特异度分别是89%、93%.四者用于BPH诊断时灵敏度分别是8%、86%、68%、43%,特异度分别是23%、92%、84%、79%,联合应用时灵敏度及特异度分别是96%、100%.结论 CK19与TPO、CD56、p63相比较,用于PTC诊断时的灵敏度及特异度均高于BPH,可作为PTC诊断的重要标记物,而TPO、CD56、p63可作为BPH诊断的重要标记物.同时,四者在良恶性乳头状增生中的阳性表达率差异具有显著性,可应用于甲状腺良恶性乳头状增生的鉴别诊断,联合应用价值更高.     

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。     

甲状腺乳头状癌合并滤泡癌10例临床病理分析

目的探讨甲状腺乳头状癌(papillary thyroid carcinoma, PTC)合并滤泡癌(follicular carcinoma, FC)的临床病理特征、预后及发病机制。方法回顾性分析10例PTC合并FC的临床病理特征和免疫表型,并复习相关文献。结果 10例患者中男性3例,女性7例,发病年龄28～70岁(平均50.7岁)。10例甲状腺FC均为单发,瘤体最大径为1.0～8.0 cm,广泛浸润型3例,微小浸润型7例,10例均为有限血管浸润型(≤4个血管),其周围未见合并甲状腺良性病变;PTC单发者5例,多发者5例,瘤体最大径为0.2～2.2 cm,≤1.0 cm者8例,周围伴淋巴细胞性甲状腺炎、桥本甲状腺炎和结节性甲状腺肿者4例。1例合并食管鳞状细胞癌。免疫表型:10例PTC中CK19阳性,8例Galectin-3阳性,6例HMBE-1阳性,6例BRAF V600E蛋白阳性,10例CD56均阴性。结论 PTC较少与FC混合发生,预后与肿瘤是否多灶及有无伴桥本甲状腺炎等有关,其内在机制复杂且仍存在争议,在临床病理外检工作中需警惕,以避免漏诊其中一种肿瘤。     

子宫颈非典型不成熟鳞状上皮化生与子宫颈鳞状上皮内瘤变Ⅲ级形态学及增殖分化特征比较

目的 探讨子宫颈非典型性不成熟鳞状上皮化生(AIM)与子宫颈CINⅢ形态学及增殖分化特征的差异.方法 采用形态学观察,AB黏液组化染色,细胞增殖相关抗原Ki-67和角蛋白(CK)10、14免疫组化染色方法 ,观察55例原诊断为CINⅢ的病例和14例子宫颈息肉伴成熟性鳞状上皮化生(OSM)组织病理学特征,黏液残留情况,细胞增殖活性和分化程度;采用半巢式PCR检测HPV16E6DNA.结果 (1)参照Crum的组织学诊断标准,在CIN Ⅲ中有1例经组织形态观察符合AIM的诊断标准,即重新诊断为AIM;(2)根据鳞状上皮中的黏液残留情况,从55例CINⅢ中鉴别出7例AIM;(3)AIM的Ki-67表达高于OSM(P=0.022),明显低于CIN Ⅲ(P=0.000)差异有统计学意义;(4)CK10在AIM和CIN Ⅲ中的表达差异有统计学意义(P=0.000);CK14在AIM和CINⅢ组间的表达差异无统计学意义(P=1.000);(5)AIM的HPV16感染检出率为71.4%与CIN Ⅲ的榆出率85.4%相比差异无统计学意义(P=0.321).结论 在Crum的AIM形态学诊断标准基础上,结合本研究中各项指标的研究结果 ,本研究提出AIM与CIN Ⅲ的鉴别诊断依据:①核分裂象数≤15/10 HPF,位于上皮下1/3层;②病理性核分裂象罕见;③AB染色显示有黏液残留;④Ki-67 PI<50%;⑤CK10弥漫表达于除基底副基底层外黏膜上皮各层.     

左侧甲状腺髓样癌合并右侧甲状腺乳头状癌伴两种癌的淋巴结转移1例并文献复习

目的探讨甲状腺髓样癌(medullary thyroid carcinoma,MTC)合并甲状腺乳头状癌(papillary thyroid carcinoma,PTC)的临床病理特点、免疫表型、诊断及鉴别诊断。方法回顾性分析1例左侧MTC合并右侧PTC伴两种癌的淋巴结转移的临床病理及免疫表型特征,并复习相关文献。结果甲状腺左侧叶:大小3.5 cm×2.5 cm×1.0 cm,切面见实性结节,大小1.0 cm×0.8 cm,胶质结节,大小1.5 cm×1.0cm。甲状腺右侧叶:不整形,大小4.0 cm×2.5 cm×1.5 cm,切面见2枚结节,大小分别为2.5 cm×1.8 cm、1.6 cm×1.4cm。镜检:左侧叶实性结节的细胞呈片状、巢状、梁状排列,由多角形、圆形或梭形细胞组成,被不等量的纤维血管间质分隔,间质内有明显淀粉样物质;右侧叶结节呈复杂分枝乳头状结构,毛玻璃样核,核沟核内包涵体易见。免疫表型:左侧叶瘤细胞TTF-1、Calcitonin、CEA、PCK、CD56和Syn均(+),Cg A、CK19、HBME-1、Galectin-3、TG、PAX-8和S-100均(-),Ki-67增殖指数为5%;右侧叶瘤细胞CK19、HBME-1和Galectin-3均(+),TG局灶(+),PAX-8、CD56(-),Ki-67增殖指数为5%;术后随访1年,无复发及转移。结论MTC合并PTC为罕见的甲状腺肿瘤,诊断主要依据病理学形态和免疫表型,MTC需与PTC、甲状腺滤泡性肿瘤、未分化癌、低分化癌和玻璃样变性梁状肿瘤鉴别。     

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.     

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.     

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.     

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.