EBV潜伏基因产物在恶性淋巴瘤组织中的表达及意义

目的：探讨EBV潜伏基因产物在恶性淋巴瘤组织中的表达及意义。方法：用免疫组化方法对565例NHL、64例HL人体标本进行LMP－1、EBNA2对比检测并选择101例NHL进行PCR检测。结果：EBV－PCR检出率（19．8％）高于LMP－1（14．9％）,PCR阴性病例LMP－1全部为阴性,EBNA2在全部病例均为阴性,在NHL,LMP－1阳性细胞主要是免疫母细胞样细胞、R－S样细胞和R－S细胞,LMP－1阳性的R－S样细胞我数表达活化分子CD30。肠道原发恶性淋巴瘤EBV检出率较高（23．1％）。T淋巴瘤EBV检出率（23．8％）高于B淋瘤（10．2％）。结论：EBV潜伏基因产物表达情况能够反映出宿主细胞的分化程度和（或）宿主的免疫监视作用。EVB在R－S样细胞形成可能起作用。EBV感染与肠道恶性淋巴瘤的发病有关。     

肠道非霍奇金淋巴瘤与EB病毒、p53、p21ras的相关性

目的：研究肠道非霍奇金淋巴瘤（NHL）与EB病毒（EBV）感染p53、p21^ras蛋白表达及其相关性。方法：以SABC免疫组化方法检测瘤细胞p53、p21^ras基因的表达及EBV寡核苷酸探针（EBER）原位杂交。结果：19例肠道NHL好发部位小于肠下段和结肠，以单发瘤结节多见，常伴有表面溃疡形成。经免疫组化证实3例为T细胞淋巴瘤（15.79%），16例为B细胞淋巴瘤（84.21%）。依WHO分类，T细胞淋巴瘤为外周T细胞性（2／19例）和T／NK细胞性（1／19例）。EBV－EBER原位杂交3／19例有阳性表达，均为T细胞淋巴瘤，阳性细胞占肿瘤细胞的30％－80％。B细胞淋巴瘤未见阳性。p53的表达共有12例，占全部病例的63.16%，11例有p21^ras的表达，为57.9%，有8例同时检出p53和p21^ras的表达。结论；肠道淋巴瘤以B细胞淋巴瘤多发，并以惰性为多见，如为T细胞性淋巴瘤，提示多是侵袭性，且T细胞淋巴瘤与EBV相关性较高，而B细胞淋巴瘤无相关性。p53的表达与EBV感染无明显相关性，而p21^ras的表达与EBV感染似有关系。     

B细胞淋巴瘤与EB病毒关系的观察

为了了解我国非免疫缺陷相关B淋巴瘤是否与EBV有关，我们采用EBVencodedsmallRNA（EBER－1）原位杂交对127例非免疫缺陷相关B淋巴瘤进行了研究。结果显示，其中8例瘤细胞核内有EBER－1的表达（中心母细胞型4例；淋巴浆细胞样型、浆细胞型、免疫母细胞型和不能分型的高度恶性B细胞淋巴瘤各1例），检出率为6．3％。这一结果与欧美的情况一致（5％左右）．但明显低于我国何杰金病（82％）及T淋巴细胞（62％）的检出率，因此提示EBV在非免疫缺陷B淋巴瘤发病中的作用是有限的，主要致病因素还有待进一步研究。     

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。     

鼻及咽部非霍奇金淋巴瘤158例临床特点及其与EB病毒感染的关系

目的探讨鼻及咽部原发性非霍奇金淋巴瘤（NHL）的临床特点、免疫表型及其与EB病毒感染的关系。方法对158例鼻及咽部原发性NHL进行了HE和免疫组织化学SP法（CD3、CD20、CD56、CD57）检查,按WHO2001年《造血和淋巴组织肿瘤的病理学和遗传学》标准进行分类;并对其中99例进行了EBER-1原位杂交的检测。结果158例鼻及咽部原发性NHL中,原发于鼻腔84例（53．2％）,扁桃体39例（24．7％）,咽部35例（22．1％）。结外鼻型NK／T细胞淋巴瘤101例（63．9％）、非特异性外周T细胞淋巴瘤23例（14．6％）,B细胞淋巴瘤34例（21．5％）。99例EBER-1原位杂交结果显示阳性率：结外鼻型NK／T细胞淋巴瘤为98．6％（70／71）,而非特异性外周T细胞淋巴瘤为66．7％（8／12）,B细胞淋巴瘤为43．8％（7／16）。结论鼻及咽部NHL中结外鼻型NK／T细胞淋巴瘤最为多见,与EB病毒密切相关,其病理诊断需结合其免疫表型特征及肿瘤部位。     

广西口腔颌面颈部原发性淋巴瘤 EBV感染及其临床病理特征分析

目的：探讨广西地区EBV感染与恶性淋巴瘤病理类型及发病的相关性。方法采用原位杂交技术检测81例口腔颌面颈部淋巴瘤的肿瘤组织中EBV编码的RNA(EBER),并分析其临床病理特征。结果(1)EBER总阳性率为44．4%,霍奇金淋巴瘤占检出率的40%,非霍奇金淋巴瘤占检出率的45．1%,不同细胞来源的非霍奇金淋巴瘤依次占检出率的75%( T细胞淋巴瘤)、87．5%( NK/T细胞淋巴瘤)、2．9%( B细胞淋巴瘤),T细胞、NK/T细胞非霍奇金淋巴瘤EBER阳性率比B细胞非霍奇金淋巴瘤高,差异有统计学意义(P<0．05)。(2)淋巴结内、外淋巴瘤EBER阳性率分别为17．9%、58．5%,二者比较差异有显著性(P<0．05)。(3)50岁以上淋巴瘤患者EBER检出率(36．2%)低于50岁以下患者检出率(55．9%),差异无显著性(P>0．05)。结论广西地区口腔颌面颈部淋巴瘤与EBV感染相关,其中以发生在淋巴结外弥散淋巴组织的NK/T细胞淋巴瘤最为显著。     

富于T细胞/组织细胞的B细胞淋巴瘤的诊断

目的：探讨富于T细胞／组织细胞B细胞淋巴瘤（TCRBCL）的诊断。方法：用S－P石蜡免疫组化法检测22例依据形态学诊断的霍奇金淋巴瘤细胞和背景细胞的免疫表型。结果：4／22例是TCRBCL,3例富于T小淋巴细胞,1例富含组织细胞;瘤细胞3例呈中心母细胞样和免疫母细胞样。1例呈腔隙型细胞样,弥漫散在分布。免疫组化瘤细胞呈CD20（＋）、CD15（－）、CD30（－）、CD21（－）、vimentin(-)。背景细胞CD45RO（＋）／CD68（＋）细胞占绝对优势,为浸润细胞的70％－90％;CD20（＋）细胞散在,CD57（＋）稀少。16例为经典型霍奇金淋巴瘤（CHL）,瘤细胞为CD15（＋）（75％）、CD30（＋）（100％）、vimentin( )(19%)、CD21（－）、CD20（－）及CD45（－）,背景细胞CD45RO（＋）和CD20（＋）数量基本相等,CD57（＋）较少。1例为结节性淋巴细胞为主型霍奇金淋巴瘤（NLPHL）,瘤细胞呈CD20（＋）、CD45（＋）、CD30（－）、CD15（－）,而背景细胞中CD57（＋）较多。结论：石蜡免疫组化在TCRBCL诊断中起重要作用,而且也应用于CHL、NLPHL及TCRBCL间鉴别诊断。     

小B细胞恶性淋巴瘤形态学和免疫组织化学研究

目的：探讨各种小B细胞恶性淋巴瘤的形态学、免疫表型特征及其鉴别诊断。方法：对15例小淋巴细胞性淋巴瘤（SLL）、3例淋巴浆细胞性淋巴瘤（LPL）、36例滤泡性淋巴瘤（FL）、25例套细胞淋巴瘤（MCL）、7例淋巴结边缘区B细胞淋巴瘤（MZL）和30例黏膜相关淋巴细胞型结外边缘区B细胞淋巴瘤（MALT－MZL）的石蜡切片进行HE形态学观察和CD5、CD10、CD23和cyclinD1等抗体的免疫组织化学分析。结果：各种小B细胞恶性淋巴瘤在组成细胞和组织结构上各具特征；免疫表型：SLL表达CD5（82％）和CD23（80％），FL表达CD10（87％），MCL表达cyclinD1（84％）和CD5（80％），MZL／MALT－MZL和LPL均不表达CD5、CD10、CD23和cyclinD1。结论：各种小B细胞恶性淋巴瘤均是独立疾病，各具形态学和免疫表型特征，结合HE形态学观察和CD5、CD10、CD23、cyclinD1等免疫组化分析有助于正确诊断和鉴别诊断。     

鼻NK/T细胞淋巴瘤--15年研究报道

目的 :探讨鼻NK/T细胞淋巴瘤 (原诊断为“中线恶性网织细胞增生症”)的临床病理及免疫表型特征、病变性质及其与EB病毒感染的关系。方法 :过去 15年中对近 2 0 0例“中线恶网”病例做了一系列研究 ,包括临床病理分析、LSAB法免疫组化染色作免疫表型分析、用PCR技术作T细胞受体β和γ链基因重排及EBV DNA检测、EBER原位杂交和原位末端标记DNA片段技术检测细胞凋亡。结果 :①鼻NK/T细胞淋巴瘤有特征性临床及病理形态学表现 ;②瘤细胞表达CD3ε:89 8% ;CD45RO :81 2 % ;CD5 6 :81 2 % ;TIA 1:10 0 %。不表达B淋巴细胞和组织细胞分化抗原 ;③TCR β链基因重排检出率为85 7% ,TCR γ链基因重排检出率为 94 45 % ;④EBV DNA检出率为 6 7 86 % ;EBER原位杂交阳性率为 90 6 3% ;⑤肿瘤组织中的凋亡细胞与Ki 6 7 呈明显正相关 (P <0 0 0 6 3) ,Ki 6 7 细胞数量变化与患者的平均生存期有明显关系 (P <0 0 2 )。结论 :“中线恶网”实为EB病毒相关、细胞毒性NK/T细胞淋巴瘤。     

人T淋巴细胞通过整联蛋白α4/VCAM-1和LFA-/ICAM-1及ICAM-2与人扁桃体生发中心结合

该文为阐明介导T细胞与淋巴细胞组织不同区域结合的粘附分子的作用，应用原位杂交粘附实验及抗体封闭试验，检测T细胞与人扁桃体组织的结合。选用针对不同抗原的单克隆抗体：CD4（13B8．2），CDlla（25．3．1），CD18（7E4）．CD28（CD28．2），CD29（K20），CD45RA（ALBll），CD49d（HP2／1），CD54（84H10），CD102（B－TI），CD106（IGll）及鼠IgM抗体；细胞选用MOLT－4，JurkatT细胞系细胞和健康人活化的T淋巴细胞。细胞培养15至20天，流式细胞仪测定表明：CD3“细胞大于98％，CD19“细胞和CD14“细胞均小于05％…     

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.     

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.     

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.     

'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.     

Der Einfluß von Nahrungsmitteln und Rauchen auf die klinisch-chemische Diagnostik von Phäochromozytom,Neuroblastom und Karzinoid-Syndrom

Zusammenfassung Der Einfluß von verschiedenen Nahrungsmitteln auf Methoden zur Bestimmung von Adrenalin (AD), Noradrenalin (NA), Vanillinmandelsäure (VMS), Metanephrinen (MN), Homovanillinsäure (HVS) und 5-Hydroxyindolessigsäure (5-HIE) im 24 h-Harn zur Diagnose des Phäochromozytoms bzw. Karzinoid-Syndroms wurde untersucht. Die in die Untersuchung einbezogenen Nahrungsmittel waren: Tee, Kaffee, Mandeln, Ananas, Käse, Walnüsse, Vanillepudding, Bananen, Tomaten und Milchschokolade. Außerdem wurde der Einfluß des Zigarettenrauchens auf die Bestimmung von AD, NA, VMS und MN untersucht.Walnüsse führten zu einer starken Erhöhung der 5-HIE-Ausscheidung. Bananen erhöhten die Ausscheidung von AD, NA, VMS, MN und 5-HIE. Kaffee und Ananas bewirkten eine geringe Zunahme der MN-Werte. Rauchen von 20–30 Zigaretten/Tag beeinflußte keine der vier Variablen.Wenn die beschriebenen Methoden benutzt werden, sollte lediglich auf den Verzehr von Bananen und Walnüssen vor und während der Harnsammelperioden verzichtet werden, da die oberen Normgrenzen im Harn überschritten werden könnten. Ein Verzicht auf Kaffee und Ananas in normalen Mengen ist nicht erforderlich. Es besteht kein Anlaß, weiterhin die bisherigen umfangreichen Restriktionen der übrigen Nahrungsmittel beizubehalten.