种痘水疱病样淋巴组织增生性疾病11例临床病理分析

目的探讨种痘水疱病样淋巴组织增生性疾病(hydroa vacciniforme-like lymphoproliferative disease,HV-LPD)的临床病理学特点、诊断及鉴别诊断。方法收集11例HV-LPD的临床资料并进行形态学观察,应用免疫组化、EB病毒(Epstein-Barr virus,EBV)原位杂交检测和T细胞受体基因重排检测,并复习相关文献。结果 11例患者发病年龄2~50岁,临床表现为头面部和(或)躯干部位的肿胀、水疱、斑丘疹、结痂、瘢痕数月至数年,伴或不伴发热、肝脾及淋巴结肿大等症状。病理形态学示淋巴样细胞浸润真皮或至皮下组织,细胞小至中等大,轻至中度异型性,围绕皮肤附件浸润和嗜血管生长。11例病变细胞CD3、CD4均阳性,TIA-1(9/11)、CD8(8/11)、Granzyme B(6/11)、CD56(1/11)阳性,EBER均阳性。7例标本TCR克隆性重排检测阳性。11例患者临床治疗方案不同,包括抗病毒、抗感染、激素、免疫抑制剂、化疗,5例患者病情稳定,2例患者病情持续,1例死亡,3例失访。结论 HV-LPD是发生于儿童的EBV相关性T细胞淋巴组织增生性疾病,临床少见,亦可见于成人,其表现多样且独特,临床病史尤其以皮损特点是重要的诊断线索,结合病理形态、免疫表型、EBV原位杂交、T细胞受体基因重排可确诊。     

皮下脂膜炎样T细胞淋巴瘤的免疫表型、基因重排检测及其在诊断中的意义

目的 探讨免疫表型和基因重排检测在皮下脂膜炎样T细胞淋巴瘤(SPTL)的诊断和鉴别诊断中的意义.方法 参照2005年世界卫生组织-欧洲癌症研究与治疗组织(WHO-EORTC)皮肤淋巴瘤分类标准收集20例SPTL.采用10种抗原标记进行免疫表型检测,运用PCR技术检测TCRγ、IgH基因重排,并用EB病毒编码的小RNA1/2(EBER1/2)原位杂交检测EB病毒感染.结果 (1)本组病例中男9例、女11例,平均年龄29.5岁;(2)所有病例的瘤细胞均表达1个或多个T细胞分化抗原(CD2、CD3或CD45RO),18/19病例表达BF1,18/20病例表达CD8,20/20、16/20病例分别表达细胞毒颗粒相关蛋白TIA-1、颗粒酶B,瘤细胞不表达CD4、CD20和CD56;(3)16/20病例检出TcRγ基因重排,未检出IgH基因重排;(4)5/20病例EBERl/2原位杂交阳性.结论 SPTL的瘤细胞具有克隆性TCR基因重排,综合临床病理、免疫表型及基因重排检测有助于本病确诊.     

C型凝集素样自然杀伤(NK)细胞受体在结外鼻型NK/T细胞淋巴瘤中表达及意义

目的 探讨C型凝集素样自然杀伤(NK)细胞受体CD94和NKG2在结外鼻型NK/T细胞淋巴瘤中的表达及意义.方法 运用逆转录聚合酶链反应(RT-PCR)检测C型凝集素样NK细胞受体CD94和NKG2在经组织形态、免疫组织化学、EB病毒原位杂交及T细胞受体PCR克隆性重排分析确诊的21例结外鼻型NK/T细胞淋巴瘤以及对照组同部位B细胞淋巴瘤8例、淋巴结外周T细胞淋巴瘤(PTCL)10例、脾脏5例、胸腺5例和慢性炎性鼻黏膜5例组织中的表达情况并进行随访.结果 21例结外鼻型NK/T细胞淋巴瘤具有典型的形态学改变,表达CD3ε、CD56和细胞毒蛋白,TCR重排阴性,20例EB病毒阳性;RT-PCR扩增结果显示,在21例结外鼻型NK/T细胞淋巴瘤中,18例(85.7%)CD94呈阳性表达;NKG2总阳性率为95.2%(20/21),各亚基表达阳性率依次为NKG2A/2B(85.7%)、NKG2D(61.9%)、NKG2F(14.3%)、NKG2C,/2E(4.8%).对照组中PTCL和B细胞淋巴瘤均不表达CD94和NKG2,仅2例脾脏和2例慢性炎性鼻黏膜组织表达CD94,1例脾脏组织表达NKG2A/2B,1例胸腺组织表达NKG2D.CD94和NKG2在结外鼻型NK/T细胞淋巴瘤中的表达与T细胞淋巴瘤和B细胞淋巴瘤比较,差异均有统计学意义(P均<0.01).CD94和NKG2同时表达于17例结外鼻型NK/T细胞淋巴瘤,共表达率为81.0%(17/21).结论 CD94和NKG2在结外鼻型NK/T细胞淋巴瘤中呈特异性和顺序性表达,提示多数病例肿瘤细胞处于活化和功能NK细胞阶段.对这些分子的检测有可能成为NK细胞源性淋巴瘤诊断的重要手段.     

儿童及青少年原发性中枢神经系统T细胞淋巴瘤5例临床病理学分析

目的探讨儿童及青少年原发性中枢神经系统T细胞淋巴瘤(PCNSTCL)的临床病理特征, 以提高对本病的认识。方法收集郑州大学第一附属医院2016年12月至2021年12月数据库里确诊的儿童及青少年PCNSTCL病例5例, 对其临床特征、病理学特征、免疫表型及分子病理学特征进行观察, 并复习相关文献。结果 5例患者中, 男性2例, 女性3例, 年龄范围在11～18岁, 中位年龄14岁。2例诊断为非特指型外周T细胞淋巴瘤, 2例诊断为间变性淋巴瘤激酶(ALK)阳性的间变性大细胞淋巴瘤, 1例诊断为NK/T细胞淋巴瘤。病理学特征:肿瘤细胞弥漫性生长, 组织学形态谱系较广, 可以是小、中、大的细胞, 局部可见肿瘤细胞围绕血管壁生长。免疫组织化学及原位杂交:4例表达CD3, 1例表达缺失;4例CD5表达缺失, 1例未缺失;2例同时表达ALK及CD30;1例表达CD56及EB病毒编码的RNA阳性;5例均表达细胞毒性标志物T细胞胞质内抗原1及颗粒酶B;3例Ki-67阳性指数>50%。2例进行T细胞受体(TCR)基因重排检测, 显示单克隆性增生。结论 PCNSTCL较为少见, 发生于儿童及青少年的...     

混合性经典型霍奇金淋巴瘤合并T细胞淋巴瘤一例

混合性淋巴瘤是指两种不同类型的淋巴瘤同时发生。该例患者男性,44岁,因无意中发现左颈部肿物入院,彩超提示左颈部4 cm大小肿物。镜下见弥漫小淋巴细胞间散在核大异型细胞。免疫组织化学显示散在核大细胞CD15、CD30、MUM1、PAX5等标记阳性,EB病毒编码的小RNA(EBER)显色原位杂交(CISH)检测显示核大细胞阳性,符合经典型霍奇金淋巴瘤。免疫组织化学显示背景小淋巴细胞CD3、CD2、CD7等标志物阳性,EBER CISH检测显示部分细胞阳性,T细胞受体基因检测提示2个位点单克隆重排,符合T细胞淋巴瘤。混合性淋巴瘤治疗不同于普通的淋巴瘤,需要综合制定化疗方案。     

混合性经典型霍奇金淋巴瘤合并T细胞淋巴瘤一例

混合性淋巴瘤是指两种不同类型的淋巴瘤同时发生。该例患者男性, 44岁, 因无意中发现左颈部肿物入院, 彩超提示左颈部4 cm大小肿物。镜下见弥漫小淋巴细胞间散在核大异型细胞。免疫组织化学显示散在核大细胞CD15、CD30、MUM1、PAX5等标记阳性, EB病毒编码的小RNA(EBER)显色原位杂交(CISH)检测显示核大细胞阳性, 符合经典型霍奇金淋巴瘤。免疫组织化学显示背景小淋巴细胞CD3、CD2、CD7等标志物阳性, EBER CISH检测显示部分细胞阳性, T细胞受体基因检测提示2个位点单克隆重排, 符合T细胞淋巴瘤。混合性淋巴瘤治疗不同于普通的淋巴瘤, 需要综合制定化疗方案。     

胃T细胞淋巴瘤临床病理观察

目的 探讨胃T细胞淋巴瘤的临床病理学特点.方法 收集7例胃T细胞淋巴瘤病例标本,对其进行了临床病理分析、免疫组织化学检测、EBER原位杂交检测及T细胞受体(TCR)基因重排检测.结果 7例病例中6例为男性,1例为女性,平均发病年龄为45岁.6例可获得资料的病例中,1例有长期腹泻史,5例有低蛋白血症.组织学上,7例标本中,有5例表现为肿瘤细胞体积较大而不一致,2例表现为大小一致的中等细胞.1例病例可见肿瘤细胞浸润腺上皮.所有病例的肿瘤组织均不表达CD20及CD79a.7例病例中,各有6例表达CD3及T细胞胞质内抗原,各有4例表达CD5、βF-1及CD30,有3例表达CDM,各有1例病例表达CD8、CD56、问变性淋巴瘤激酶及粒酶B.7例病例肿瘤细胞EBER原位杂交检测均为阴性且都存在TCR基因克隆性重排.结论 胃T细胞淋巴瘤是一种少见的恶性淋巴瘤,具有独特的临床病理特点.     

儿童种痘水疱病样淋巴组织增生性疾病临床病理分析

目的探讨儿童种痘水疱病样淋巴组织增生性疾病的临床病理学特征、诊断、鉴别诊断及预后。方法收集6例儿童种痘水疱病样淋巴组织增生性疾病,观察其临床表现、组织病理学、免疫表型及相关分子病理检测,收集随访资料并复习相关文献。结果男童4例,女童2例,病史1个月~4年。临床均表现为反复发作的水痘样疱疹并伴发热。镜下见表皮内有水疱形成或伴坏死,真皮层至皮下脂肪层内有数量多少不等的淋巴样细胞浸润,细胞可为轻至中度异型,多位于小血管及附属器周围。免疫组化示异型细胞可表达CD2、CD3、CD5、CD7、CD43、CD4、CD8、TIA-1,仅1例表达CD56,所有病例均不表达CD20、Pax-5。Ki-67增殖指数平均42.3%。5例EBER原位杂交检测呈阳性,2例TCR克隆性重排阳性。5例获得随访,1例患儿死亡。结论儿童种痘水疱病样淋巴组织增生性疾病临床较为少见,与慢性活动性EB病毒感染密切相关,临床过程可能为独立的疾病谱系,其性质可为良性、交界性及恶性。病理诊断需密切结合临床表现。     

Ig/TCR基因重排分析联合EBER原位杂交检测在原发性胃肠道淋巴瘤诊断中的应用

目的 探讨Ig/TCR基因重排分析联合EBER原位杂交检测在原发性胃肠道淋巴瘤(gastrointestinal lymphomas,GIL)中的诊断价值.方法 选取常规石蜡包埋的GIL病理标本35例(包括成熟B淋巴细胞肿瘤29例,成熟T淋巴细胞和NK细胞肿瘤6例),淋巴结反应性增生病变10例,提取DNA,应用BIOMED-2引物系统进行Ig/TCR基因重排的克隆性分析,并采用原位杂交方法检测EB病毒编码的小RNA(EBER).结果 35例GIL中,共检测出34例克隆性重排.其中29例成熟B细胞淋巴瘤均扩增出Ig克隆性重排,敏感性为100%,且联合应用IgH与IgK引物Ig单克隆性重排的检出率最高;6例成熟T淋巴细胞和NK细胞肿瘤中5例扩增出TCR克隆性重排,敏感性为83.3%;10例淋巴结反应性增生病例均未检测到Ig及TCR克隆性重排条带,其检测特异性为100%.29例成熟B细胞淋巴瘤及10例淋巴结反应性增生组织经EBER原位杂交检测均为阴性,6例成熟T淋巴细胞和NK细胞肿瘤中2例EBER原位杂交检测阳性,且均为鼻型NK/T细胞淋巴瘤.结论 BIOMED-2标准化的基因重排分析系统检测石蜡包埋组织中Ig基因和TCR基因克隆性重排的敏感性和特异性均很高,对GIL的诊断和鉴别诊断具有重要的临床应用价值,EBER原位杂交检测对基因克隆性重排阴性的淋巴瘤也具有一定的辅助诊断作用.     

EB病毒相关与不相关的肠道T细胞淋巴瘤临床病理研究

目的：探讨EB病毒相关与不相关的肠道T细胞淋巴瘤的临床病理特征、免疫分型和肿瘤细胞属性。方法：运用EBER1／2原位杂交检测EB病毒感染,采用免疫组化检测32例肠肠道原发T细胞淋巴瘤的免疫表型以及LMP－1、TIA－1、bcl-2和CD21的表达。结果：（1）27例（84．4％）为EB病毒相关淋巴瘤,其中11例（40．75）表达LMP－1。（2）32例瘤细胞均表达CD45RO,CD8＋。4例（12．5％）,CD4＋8例（25．0％）,CD56＋9例（28．1％）,17例（53．7％）为CD4－、CD8－、CD56－。TIA－1＋31例（96．9％）。无1例表达bcl2-,CD21。形态上28例为多形性中一大细胞性,单形性中等大细胞性和多形性各2例。临床上多见于青壮年男性,以腹痛、便血、发热、体重下降为主要症状,预后较差（中位生存期1．7月）。（3）EB病毒相关与相关者出现便血和发热以及CD3,CD8、CD56的表达方面差异有显著性。结论：在我国,绝大多数肠道T细胞淋巴瘤为EB病毒相关,具有特殊临床病理表现和免疫表型。其肿瘤细胞源自不同T细胞亚群（包括细胞毒性T细胞）或者NK细胞。     

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.