FLI-1在小圆细胞肿瘤鉴别诊断中的应用

目的研究FLI-1和CD99在小圆细胞肿瘤中的表达情况,探讨二者在小圆细胞肿瘤鉴别诊断中的应用价值。方法对46例小圆细胞肿瘤进行FLI-1和CD99免疫组化标记,并结合临床与病理组织学进行对比研究。结果FLI-1在Ewing肉瘤／外周原始神经外胚叶肿瘤（EWS／PNET）中阳性表达率为90．5％（19／21）,在分化差的滑膜肉瘤、横纹肌肉瘤分别为14．3％（1／7）、22．2％（2／9）,而在嗅神经母细胞瘤和间叶软骨肉瘤均无表达。CD99在EWS／PNET中阳性表达率为95．2％（20／21）,在分化差的滑膜肉瘤、横纹肌肉瘤、嗅神经母细胞瘤和间叶软骨肉瘤分别为71．4％（5／7）、66．7％（6／9）、75．0％（3／4）和60％（3／5）。FLI-1标记在EWS／PNET的敏感性为90．5％,特异性为88％;而CD99在EWS／PNET的敏感性为95．0％,特异性为32％。FLI-1在EWS／PNET中的特异性明显高于CD99（P〈0．05）。结论FLI-1在EWS／PNET诊断中的价值优于CD99,并且可用于小圆细胞肿瘤的鉴别诊断。     

联合运用BCL-10和Trypsin在胰腺腺泡细胞癌诊断和鉴别诊断中的作用

目的探讨联合运用BCL-10和Trypsin在胰腺腺泡细胞癌(pancreatic acinar cell carcinoma, PACC)、胰腺神经内分泌肿瘤(pancreatic neuroendocrine tumors, PNET)及胰腺实性假乳头肿瘤(solid pseudopapillary neoplasm, SPN)中的诊断和鉴别诊断作用。方法收集安徽医科大学第一附属医院病理科2014～2018年已确诊的46例胰腺肿瘤相关病例,其中7例PACC来自复旦大学附属中山医院病理科及皖南医学院弋矶山医院病理科,采用免疫组化EnVision两步法检测BCL-10、Trypsin、CD10、β-catenin、CgA、Syn在PACC、PNET和SPN中的表达。结果 BCL-10、Trypsin在PACC中的阳性率分别为80.0%和70.0%,在SPN中均阴性;BCL-10在PNET中均阴性,Trypsin在PNET中的阳性率为18.8%。CgA、Syn在PNET中的阳性率分别为100.0%和93.7%,在PACC和SPN中的阳性率较低(0～40.0%)。在SPN中CD10阳性率和β-catenin核阳性率分别为95.0%和100.0%,β-catenin在另外两种肿瘤中主要呈散在胞膜弱阳性,胞核阳性率较低(10.0%～25.0%)。BCL-10和Trypsin在PACC中的敏感性分别为80.0%、70.0%,特异性分别为94.7%、91.7%。联合使用BCL-10和Trypsin的敏感性和特异性分别为90.0%、97.1%。结论与传统指标Trypsin相比,BCL-10对PACC的诊断具有较高的敏感性和特异性,联合运用BCL-10和Trypsin对PACC、PNET及SPN的鉴别诊断具有重要价值。     

组织细胞坏死性淋巴结炎中CD123及MPO的表达及意义

目的探讨CD123和MPO在组织细胞坏死性淋巴结炎(histiocytic necrotizing lymphadenitis,HNL)中的表达及在诊断和鉴别诊断中的价值。方法对39例HNL进行常规形态学观察和免疫组化标记,12例淋巴组织反应性增生性病变和12例弥漫性大B细胞淋巴瘤作为对照。结果 CD123在HNL中的阳性率为89.7%,淋巴组织反应性增生性病变中的阳性率为33.3%(P<0.01),弥漫性大B细胞性淋巴瘤中的阳性率为16.7%(P<0.01),其CD123敏感性为90%,特异性为75%;MPO的敏感性为82%,特异性为88%,两者联合应用,其敏感性为79%,特异性为96%。结论 CD123和MPO在HNL中均具有较高的阳性率,其敏感性和特异性均较好,具有很好的诊断和鉴别诊断价值,是诊断HNL较为理想的免疫标记物。     

梭形细胞肿瘤中CD56的表达及其诊断意义

目的探讨CD56在梭形细胞肿瘤中的表达及其诊断意义。方法采用免疫组化EnVision两步法检测137例梭形细胞肿瘤中CD56的表达,其中包括40例平滑肌肿瘤、20例横纹肌肉瘤、23例外周神经源性肿瘤及54例其它梭形细胞肿瘤。结果CD56在平滑肌肿瘤、横纹肌肿瘤、外周神经源性肿瘤及其它梭形细胞肿瘤中的阳性率分别为47.50%(19/40)、95%(19/20)、95.65%(22/23)、24.07%(13/54)。横纹肌肿瘤、外周神经源性肿瘤中CD56的阳性率明显高于平滑肌肿瘤及其他梭形细胞肿瘤组,差异有显著性(P<0.01);平滑肌肿瘤中CD56的阳性率与其它梭形细胞肿瘤组相比,差异无显著性(P>0.01);横纹肌肿瘤中CD56的阳性率与外周神经源性肿瘤组相比,差异无显著性(P>0.01)。结论 CD56在外周神经源性肿瘤和横纹肌肿瘤中的敏感性高,可以作为一项有效的鉴别指标。     

胰腺实性-假乳头状肿瘤和神经内分泌肿瘤中Claudin5和Claudin7的表达及意义

目的探讨Claudin5和Claudin7在胰腺实性-假乳头状肿瘤(solid-pseudopapillary neoplasm,SPN)、神经内分泌肿瘤(neuroendocrine tumor,NET)中的表达及意义。方法采用免疫组化En Vision法检测20例SPN和23例NET中β-catenin、CD10、CK、vimentin、CD99、NSE、Syn、PR、Claudin5和Claudin7的表达。结果 (1)在SPN和NET中β-catenin、CD10、CK、vimentin、CD99、NSE、Syn、PR呈不同程度阳性表达。其中,β-catenin和CD10在SPN和NET中的阳性率差异有统计学意义(P0.05),β-catenin诊断SPN的敏感性为90.0%,特异性为52.2%;CD10诊断SPN的敏感性为80.0%,特异性为69.6%。其余6种标志物差异无统计学意义(P0.05)。(2)Claudin5在SPN中的阳性率为100%(20/20),明显高于NET(13.0%,3/23),差异有统计学意义(P0.05);其诊断SPN的特异性(100%)和敏感性(87.0%)均高于β-catenin和CD10。(3)Claudin7在胰腺NET中的阳性率为100%(23/23),而在所有SPN中均不表达;其诊断NET的特异性和敏感性均为100%。结论 Claudin5和Claudin7分别在SPN和NET中呈肿瘤细胞胞膜阳性表达模式,是两者的免疫组化特征。联合检测Claudin5、β-catenin、CD10和Claudin7有助于诊断和鉴别诊断SPN和NET。     

NKX3.1和NKX2.2在间叶性软骨肉瘤中的表达及诊断价值

目的探讨NKX3.1和NKX2.2在间叶性软骨肉瘤(mesenchymal chondrosarcoma, MC)中的免疫组织化学表达情况及两者在MC和其他类型小圆细胞恶性肿瘤中的鉴别诊断价值。方法收集解放军东部战区总医院2001—2020年诊断的12例MC和97例其他小圆细胞恶性肿瘤, 进行NKX3.1和NKX2.2免疫组织化学检测, 其中在12例MC中采用两种NKX3.1抗体[兔多克隆抗体和兔单克隆抗体(克隆号EP356)]进行检测, 在97例其他小圆细胞恶性肿瘤中采用一种NKX3.1抗体(兔多克隆抗体)进行检测, 并复习相关文献。结果 12例MC患者女性7例, 男性5例, 平均年龄33岁(范围14～54岁)。其中9例来源于骨, 3例来源于软组织。12例MC患者8例术后出现复发或转移, 其中3例死亡。12例MC组织学上均具有典型的双向分化特征。免疫表型上, NKX3.1两种抗体在MC中的阳性比例均为12/12;NKX3.1(兔多克隆抗体)在12例软骨肉瘤(3级)、5例腺泡状横纹肌肉瘤、5例胚胎性横纹肌肉瘤和5例孤立性纤维性肿瘤中各1例局灶弱阳性, 余70例其他小圆细胞恶性肿瘤均阴性...     

胃肠胰食管神经内分泌肿瘤中NKX2．2蛋白的表达

目的：检测NKX2．2蛋白在胃肠胰食管神经内分泌肿瘤中的表达,探讨其表达与临床病理特征的关系。方法采用免疫组化法检测41例胃肠胰食管神经内分泌肿瘤中NKX2．2、Syn及CgA的表达,并复习相关文献。结果 NKX2．2蛋白阳性定位于细胞核,在7个原发部位的神经内分泌肿瘤中均有不同程度的表达,在4例正常胰腺胰岛细胞中弥漫强阳性表达, NKX2．2、Syn及CgA在小肠、直肠及胰腺神经内分泌肿瘤中的总阳性率分别为100%、100%、46．7%;NKX2．2在前肠、中后肠的阳性率分别为30%和87%,差异有统计学意义(χ2=11．09,P=0．001)。 NKX2．2蛋白表达与患者性别、年龄、分级、肿瘤最大径及淋巴结转移无明显相关性。结论 NKX2．2作为一种新型的神经内分泌标志物,在诊断小肠、直肠及胰腺神经内分泌肿瘤上明显优于CgA,联合检测NKX2．2、Syn、CgA可提高小肠、直肠及胰腺神经内分泌肿瘤诊断的准确性。     

Arginase-1联合Glypican-3在肝细胞肝癌和非肝脏来源肿瘤鉴别诊断中的意义

目的观察肝细胞肝癌(hepatocellular carcinoma,HCC)、非肝脏来源肿瘤组织中精氨酸酶-1(Arginase-1,Arg-1)、磷脂酰肌醇蛋白聚糖-3(Glypican-3,GPC-3)的表达及在病理诊断和鉴别诊断中的作用。方法收集156例HCC、5例胆管细胞癌、20例肝脏转移癌和18例其他部位恶性肿瘤,应用免疫组化En Vision法检测两种蛋白的表达。结果 Arg-1在HCC及非肝脏来源肿瘤中的阳性率分别为93.6%(146/156)和0(0/43),在HCC中的阳性率随着肿瘤分化程度的降低而减少(r=-0.264,P=0.001);GPC-3在HCC及非肝脏来源肿瘤中的阳性率分别为90.4%(141/156)和14.0%(6/43),在HCC中的阳性率随着肿瘤分化程度的降低而增加(r=0.179,P=0.026)。Arg-1和GPC-3的敏感性、特异性、阳性预测值和阴性预测值分别为93.6%、100%、100%、81.1%和90.4%、86.0%、96.0%、71.2%。结论 Arg-1是敏感和特异的肝细胞标志物,对鉴别肝脏源性和非肝脏源性肿瘤有显著优势;GPC-3是诊断HCC特异性较高的标志物,尤其在低分化HCC的鉴别诊断中更有优势;联合应用Arg-1和GPC-3,对于HCC与肝脏转移癌的诊断与鉴别诊断具有重要意义。     

胃肠道间质瘤64例免疫标记物应用分析

目的 探讨胃肠道间质瘤(gastrointestinal stromal tumor,GIST)的免疫组化标记物的表达特征,为其诊断及鉴别诊断提供依据.方法 收集85例确诊的胃肠道及腹、盆腔间叶源性肿瘤标本,其中GIST 64例.免疫组化法检测CD117、CD34、DOG1、NSE、S-100、SMA和vimentin的表达.结果 GIST组中CD117、CD34、DOG1、NSE阳性率分别为89.1%、76.6%、96.9%及87.5%;非GIST组中的阳性率分别为4.8%、33.3%、28.6%和50.0%.CD117阴性的GIST组中CD34、NSE、DOG1阳性率分别为28.6%、71.4%和85.7%.结论 GIST中DOG1表达的敏感性高于CD117,在CD117阴性的病例中DOG1优于其他标记物.DOG1与CD117及NSE等联合应用于免疫组化检测足以明确绝大多数GIST的诊断.     

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.     

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.