恢复期SARS患者淋巴细胞亚群分布及其与T淋巴细胞Ag-NOR含量相关性的初步分析

目的　通过检测恢复期SARS患者外周血淋巴细胞亚群分布及其与T淋巴细胞核仁形成区嗜银蛋白 (Ag NOR)含量的相关性分析 ,探讨恢复期SARS患者的免疫状态及淋巴细胞亚群与活性状态改变的关系。方法　以流式细胞术检测患者外周血淋巴细胞亚群 ,用KL型免疫图像分析系统检测外周血T淋巴细胞Ag NOR ,对两者进行相关分析。结果　恢复期患者T淋巴细胞总数及CD4 +亚群基本正常 ,而CD8+亚群偏高 ,CD4 +/CD8+降低 ,CD4 +/CD8+<1的比例占 37.4 % ,激活T细胞中以CD8+细胞为主。B细胞比例正常。NK细胞明显低于对照组。重症患者CD4 +、CD4 +/CD8+、CD1 9+CD5+降低及CD8+、CD3+HLA DR+升高。 50岁以上及使用大剂量激素患者CD3+HLA DR+升高。淋巴细胞Ag NOR的含量 (IS % )在正常范围 ,但患者IS值呈偏态分布 ,低于正常范围者占 4 4.99%。淋巴细胞Ag NOR的含量与CD3+、NK、CD3+HLA DR+、CD3+CD2 5+在统计学上具有相关性。结论　恢复期SARS患者免疫功能趋于恢复正常 ,但部分患者的淋巴细胞亚群数量及淋巴细胞活性仍未恢复正常 ,这些病人在临床症状得到改善之后 ,尚需一定时间的观察随访 ,以了解SARS病毒对人体免疫机能的长期影响。     

SLE患者外周血淋巴细胞凋亡异常及血清中IL-10的影响

目的：研究SLE患者外周血单个核细胞(PBMCs)中淋巴细胞亚群的凋亡特点。方法：采用三色荧光流式细胞术检测CD3、CD4、CD8、CD19细胞亚群的早期凋亡；ELISA法检测PBMCs培养上清中的sFas、sFasL；实时荧光半定量RT-PCR方法检测细胞内FasmRNA的表达水平。结果：SLE患者PBMCs中CD3^ 细胞凋亡明显增多；CD4^ 和CD8^ 细胞亚群凋亡均有明显增加，但以CD4^ 细胞凋亡增多更为明显；相应地，其PBMCs中CD4^ 、CD8^ 细胞百分率下降，CD4／CD8比值降低。SLE患者血清可诱导CD3^ 、CD4^ 、CD8^ T细胞亚群凋亡增多，sFas、sFasL水平增高及Fas mRNA表达增加；抗-IL-10抗体则可中和SLE血清的上述作用。结论：SLE患者体内T细胞凋亡增多，以CD4^ T细胞凋亡增加更为显著，导致CD4／CD8比值下降；SLE血清中高水平的IL-10可能通过诱导Fas、FasL表达增高而促进T细胞凋亡的发生。     

淋巴细胞共刺激信号和凋亡信号异常与RA免疫效应亢进的研究

目的：探究T淋巴细胞表面多种细胞信号分子所介导的细胞活化或凋亡信号在RA患者免疫功能紊乱中的作用。方法：采用流式细胞术检测RA患者外周血T细胞亚群及其表面共刺激分子cD154（cD40L）、CD30和凋亡受体CD95（Fas）的表达。结果：RA患者外周血T细胞亚群偏移，CD4^＋T细胞增加，CD8^＋T细胞减少；共刺激分子CD154在CD4^＋和CD8^＋T细胞上的表达均上调，但CD30分子的表达均降低，并以CD4^＋T细胞降低更为明显。同时，凋亡受体CD95分子在T细胞亚群上的表达均明显增加。结论：RA患者T淋巴细胞表面多种信号分子表达异常，共同导致了RA患者免疫功能紊乱。     

顽固性咽部溃疡中T淋巴细胞亚群的分布

目的 :检测顽固性咽部溃疡 (recurrentpharyngealulcer,RPU)中T淋巴细胞亚群的分布 ,探讨T淋巴细胞介导的免疫反应在咽部溃疡复发中所起的作用。方法 :应用免疫组织化学SP技术检测RPU组 36例和正常对照组 6例咽部黏膜组织中浸润细胞CD4 、CD8 、HLA DR 的表达 ,并进行统计学分析。结果 :RPU组咽部组织黏膜中CD4 细胞较对照组明显减少 ,CD8 细胞较对照组明显增多 ,CD4 CD8 比值明显下降 (P <0 0 5 ) ;巨噬细胞、T淋巴细胞高表达HLA DR抗原 (P <0 0 5 )。结论 :顽固性咽部溃疡中有大量T淋巴细胞分布 ,且T细胞亚群比例失调 ,显示细胞免疫功能的紊乱在咽部溃疡的形成与复发中起重要作用。     

SLE患者外周血T细胞亚群凋亡特点及其相关机制的研究

目的:研究系统性红斑狼疮(SLE)患者外周血CD3+、CD4+、CD8+T细胞亚群的凋亡特点及其相关的凋亡机制。方法:采用三色荧光流式细胞术检测高活动性SLE患者、低/非活动性SLE患者以及正常对照者外周血T细胞亚群的百分比例、T细胞亚群膜表面Fas/FasL的表达率、T细胞亚群早期凋亡(AV+PI-)的情况;采用ABC-ELISA法测定各组SLE患者和正常对照者血清IL-10水平;对10例血清IL-10水平异常升高的高活动性SLE患者进行体外PBMCs培养实验,其中分别加入抗FasL抗体和抗IL-10抗体,48小时常规培养后分别检测PBMCs中T细胞亚群百分比例、T细胞亚群膜表面Fas/FasL的表达率、T细胞亚群早期凋亡的变化。结果:SLE患者外周血T细胞凋亡异常增多,其中以高活动性SLE患者CD4+T细胞亚群的凋亡尤为显著(P0.05),CD4+T细胞的异常凋亡与CD4+和CD8+T细胞膜表面表达增高的Fas/FasL密切相关(P0.05);各组SLE患者外周血血清IL-10水平均明显升高(P0.01),高活动性SLE患者更为明显,血清IL-10水平升高不仅与SLE主要临床检验指标相关,而且与CD4+/CD8+比值减少、CD4+T细胞高表达FasL相关(P0.05);随访研究显示,随着SLE病情好转、稳定,血清IL-10水平下降明显、T细胞亚群Fas/FasL的表达率明显减少、T细胞亚群凋亡逐渐减少,以上变化均在CD4+T细胞亚群中体现得最为明显(P0.05)。结论:SLE患者T细胞活动性异常升高,尤其是CD4+T细胞亚群凋亡增加,是SLE疾病发展的重要病理机制,IL-10作为能诱导T细胞高表达Fas/FasL的重要调节因子,参与了SLE患者CD4+T细胞凋亡的免疫调节,SLE患者异常增高的IL-10很可能通过Fas/FasL途径促进了T细胞尤其是CD4+T细胞亚群的凋亡。     

重症肌无力患者CD4、CD8细胞表面Fas分子的变化

为探讨Fas分子、CD4、CD8分子在重症肌无力发生中的作用 ,从胸腺及外周血分离单个核细胞 ,用荧光标记的单克隆抗体 (Fas FITC、CD4 PE、CD8 Cy )和流式细胞仪检测细胞表面Fas、CD4、CD8表达情况。结果发现 ,(1)MG患者外周血单个核细胞 (PBMC )CD4 + CD8 细胞明显低于对照组 (P <0 0 2 ) ;(2 )MG患者Fas分子在PBMC的表达率明显低于对照组 (P<0 0 2 ) ,Fas+ CD4 + 细胞也低于对照组 (P <0 0 5 ) ;(3)在Fas+ 的胸腺细胞中 ,MG患者的双阳性细胞显著低于对照组 (P <0 0 1) ,而CD4 CD8+ 细胞则高于对照组 (P <0 0 5 )。说明重症肌无力患者淋巴细胞存在Fas表达异常 ,表现为外周CD4 + 细胞活化后的凋亡障碍和胸腺CD4 + CD8+ 细胞凋亡障碍 ,可能与重症肌无力患者自身反应性T细胞的形成及疾病的发生有关     

胎儿腭扁桃体T细胞亚群CD4和CD8阳性细胞的发育

目的:探讨胎儿腭扁桃体T细胞亚群CD4和CD8阳性细胞的发育.方法:收集9～28周因故终止妊娠胎儿腭扁桃体,免疫组织化学SP法显色显示CD4阳性细胞和CD8阳性细胞.结果:12周,腭扁桃体固有层内见少量CD4阳性细胞及CD8阳性细胞.14周,CD8阳性细胞数量较CD4阳性细胞增多,隐窝上皮内始见少量CD8阳性细胞和CD4阳性细胞浸润.22周,CD4阳性细胞免疫反应增强,数量仍较CD8阳性细胞少.至28周,两种阳性细胞数量逐渐增多,但以CD8阳性细胞为主,两者在固有层内散在分布或集聚成小群落,隐窝上皮内多呈单个分布.结论:12周CD4和CD8亚群已迁入胎儿腭扁桃体;随胎龄增长,两个亚群T细胞数量逐渐增多,但CD8亚群多于CD4亚群;两个亚群的T细胞发育时序基本一致.     

两次随访的康复期SARS患者T细胞亚群及其相关活化分子的研究

目的 :探讨康复期SARS患者外周血T细胞亚群及其相关活化分子的变化。方法 ::对出院后的SARS患者 ,采用统一调查问卷及实验室检测进行随访研究。两次随访中 ,应用流式细胞仪检测了我院 70余例经中西医结合治疗的康复期SARS患者外周血中CD3 、CD4 、CD8 、CD8 CD2 8 、CD8 CD2 8-、CD3 CD2 5 、CD3 CD6 9 、CD3 HLA DR T细胞的百分率及CD4 /CD8 T细胞的比率的改变 ,并以描述性分析及t检验进行比较分析。结果 :两次随访中 ,CD3 、CD4 和CD8 CD2 8 T细胞的百分率 (均值 )及CD4 /CD8 T细胞的比率 ,均明显低于正常值 (P <0 .0 5 ) ,而CD8 CD2 8-T细胞的百分率则显著增高 (P <0 .0 1)。第 2次随访中 ,检测的CD3 、CD8 、CD3 CD2 5 、CD3 CD6 9 及CD3 HLA DR T细胞的百分率 (均值 ) ,及CD4 /CD8 T细胞的比率 ,与第 1次的相比较差异较显著 (P <0 .0 1) ,其余项目差异均不明显。结论 :随着康复期的延长 ,患者的免疫功能逐渐恢复 ,病毒对T细胞活化的影响逐渐减少。     

T细胞凋亡受体和共刺激分子的表达变化与终末期肾功能衰竭患者细胞免疫功能的关系研究

目的：探究终末期肾功能衰竭患者T细胞亚群的凋亡受体CD95分子与共刺激分子CD28、CDl52（CTLA-4）的表达与细胞免疫功能的关系。方法：采用流式细胞术检测外周血T细胞的凋亡受体CD95（Fas）与共刺激分子CD28／CDl52表达。结果：终末期肾功能衰竭患者CD3^＋T细胞和CD4^＋T细胞比例明显高于健康对照组，CD4／CD8比值增加（P=0．008），CD4^＋T细胞和CD8^＋T细胞上CD95分子表达均上调（P=0．001），以CD8^＋T细胞上CD95分子增加更为明显；CD28和CD152分子在不同T细胞亚群上的表达均上调（P〈0．05），然而，CD4^＋T细胞以CD28分子表达增加为主，而CD8^＋T细胞则CD152分子表达增加为主。结论：终末期肾功能衰竭患者的细胞亚群失衡，共刺激分子CD28和CD152表达异常增加，提示T细胞活化与抑制性调节发生紊乱。T细胞亚群上凋亡受体CD95分子表达增加，以CD8^＋T细胞为主，说明终末期肾功能衰竭者淋巴细胞的减少可能通过两种途径——受体配体途径和负性共刺激分子CD152抑制信号途径，其中以CD8^＋T细胞减少为主，造成患者细胞免疫缺陷。     

尖锐湿疣患者外周血T淋巴细胞上活化抗原的表达

目的 :探讨尖锐湿疣 (CA)患者外周血CD6 9和HLA DR分子在T淋巴细胞上表达的变化及其意义。方法 :采用免疫荧光三标记流式细胞术检测 30例CA患者外周血T细胞CD6 9和HLA DR抗原的表达 ,并以 31例正常人作为对照。结果 :CA患者外周血CD3 T细胞CD6 9的表达 (6 6 3%± 3 13% )与正常人对照组 (5 12 %± 1 6 4 % )相比 ,差异有显著性 (P <0 0 5 ) ,CD4 T细胞CD6 9的表达与正常人对照组相比 ,差异无显著性 (P >0 0 5 ) ,CD8 T细胞表达CD6 9水平 (4 6 1%± 3 0 9% )明显高于对照组 (2 6 7%± 1 31% ,P <0 0 1) ;患者组CD3 T细胞中HLA DR 细胞 (2 1 6 5 %± 8 84 % )比对照组 (13 5 6 %± 5 15 % )显著增高 (P <0 0 0 1)。结论 :CA患者外周血T淋巴细胞的激活以CD8 T细胞为主 ,其免疫激活状态在抗病毒感染中起着重要作用。     

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.