CD86协同刺激信号在孕早期母—胎界面Th1／Th2型细胞因子表达调控中的作用

目的探讨CD86协同刺激信号在孕早期母-胎界面Th1/Th2型细胞因子表达调控中的作用。方法建立正常妊 娠模型CBA×Balb/c和自然流产模型CBA× DBA/2。于孕第4、6、8、10天给CBA孕鼠腹腔注射大鼠IgG作为对照组;仅于孕第4 天或于孕第4、6、8、10天给CBA孕鼠腹腔注射大鼠抗小鼠CD86 mAb。孕第14天计算两种模型各实验组胚胎吸收率R。ELISA 法测定孕第9和第14天各实验组母-胎界面组织体外培养上清中Th1/Th2型及相关细胞因子(IL-2、IFN-γ、TNF-α、IL-4、IL-10、 TGF-β2)表达水平。结果孕早期干预CD86协同刺激信号,对正常妊娠模型母-胎界面孕第9和第14天IL-4、IL-10、TGF-β2以及 IFN-γ、TNF-α表达均无显著影响,其胚胎吸收率亦无显著变化。自然流产模型中,孕早期干预CD86协同刺激信号后,孕第9、 第14天母-胎界面IL-4、IL-10、TGF-β2表达均显著增加(P＜0.05);而IFN-γ、TNF-α表达显著下降(P＜0.05)。胚胎吸收率亦 显著下降(P＜0.05)。结论孕早期母-胎界面CD86协同刺激信号的调节紊乱可能是触发母体对胚胎产生免疫排斥的重要病 理因素,于孕早期干预CD86协同刺激信号能够恢复母-胎界面Th1型/Th2型免疫调节的生理平衡,从而诱导母-胎免疫耐受。     

干预CD86协同刺激信号诱导母-胎界面Th2型免疫偏离及其对妊娠预后的影响

目的探讨干预CD86协同刺激信号在母-胎界面Th1/Th2型细胞因子表达调控及诱导母-胎免疫耐受中的作用.方法将正常妊娠模型CBA×BALB/C和自然流产模型CBA×DBA/2的CBA孕鼠均分为3组对照组于孕第4、6、8、10天腹腔注射大鼠IgG;A组于孕第4、6、8、10天腹腔注射大鼠抗小鼠CD86mAb;B组仅于孕第4天(着床期)腹腔注射大鼠抗小鼠CD86mAb.孕第9天,竞争性半定量RT-PCR测定各组母-胎界面Th1/Th2型细胞因子转录水平;孕第9、14天ELISA测定母-胎界面组织培养上清IL-4/IFN-γ比值;孕第14天比较两种模型各组的胚胎吸收率R.结果正常妊娠模型中,干预CD86协同刺激信号对母胎界面原有Th2型免疫偏离及妊娠预后均无显著影响.自然流产模型中,干预CD86协同刺激信号能够诱导母胎界面局部形成Th2型免疫偏离并显著改善其妊娠预后.结论于孕早期干预CD86协同刺激信号能够恢复母-胎界面局部Th1型/Th2型细胞因子表达的生理平衡,形成维持正常妊娠所需的Th2型免疫偏离,诱导母-胎免疫耐受.     

复发性自然流产育龄期妇女母-胎界面中细胞因子表达分析

目的:分析复发性自然流产(RSA)育龄期妇女母-胎界面中相关细胞因子表达水平变化。方法:连续选择近期就诊的RSA育龄期妇女21例,收集流产蜕膜组织,采用酶联免疫吸附法进行蜕膜组织液中IL-2、IL-4、IL-10、IFN-γ浓度等指标检测,并与同期早孕并行人工流产终止妊娠妇女(对照组,20例)相同测试结果比较。结果:RSA组蜕膜组织液IL-2和IFN-γ浓度均明显高于对照组,而IL-4和IL-10浓度则显著低于后者(P均<0.01)。结论:RSA育龄期妇女母-胎界面上存在着明确的Th1优势状态表达。     

补肾益气方对人蜕膜CD4^＋ T细胞分泌IL-4和IFN-γ的调控作用

目的:观察补肾益气方对人早孕蜕膜CD4+T细胞分泌IL-4和IFN-γ的调节作用,探讨其调节母胎界面Th1/Th2免疫保胎机制.方法:将40只成年雌性SD大鼠随机分成两组:补肾益气方组和生理盐水组,分别灌服体积相同的中药和生理盐水,早晚各一次,3天后颈动脉取血;收集孕6～10周行人工流产术的正常孕妇的蜕膜组织,用免疫磁珠方法分离出CD4+T细胞进行培养,分4组:10%胎牛血清为正常对照组(A组),10%中药血清组(B组),20%中药血清组(C组),10%生理盐水血清组(D组),分别培养24、48、72小时,以ELISA检测法检测细胞培养上清中IL-4和IFN-γ的水平.结果:与A组相比,B组和C组的Th2型细胞因子IL-4的水平均显著升高(P＜0.05);Th1型细胞因子IFN-γ的水平显著降低(P＜0.01),但是B组和C组的结果之间无显著差异.结论:补肾益气方通过促进蜕膜CD4+T分泌IL-4,并抑制其产生IFN-γ,从而促进母胎界面形成Th2优势.     

转录因子T-bet在Th1/Th2分化中的作用及意义

T-bet是属于T-box家族的新型转录因子,选择性地表达于Th1细胞,作为Th1特异的转录因子能诱导IFN-γ的产生,在Th1细胞的分化中起着决定性的作用。T-bet是IFN-γ基因强有力的转录激活剂,又能诱导并保持IL-12Rβ2的表达,且能将分化中的效应性Th2和已完全分化的Th2逆转为Th1,伴随产生大量的IFN-γ,并抑制IL-4、IL-5、IL-13等Th2型细胞因子的产生。T-bet在T细胞活化过程中能被IFN-γ诱导而上调;通过STAT1依赖的途径,TGF-β能通过抑制T-bet而抑制Th1分化。T-bet与Th1/Th2相关疾病的联系正日益受到关注。     

高迁移率族蛋白B1与原因不明复发性流产患者Th1/Th2平衡的相关性

目的 探讨HMGB1和Th1/Th2型细胞因子在原因不明复发性流产（URSA）患者外周血中的表达及相关性研究。方法 纳入2019年6月至2020年6月期间在深圳市妇幼保健院妇科就诊的100例URSA患者为URSA组,分别于免疫治疗前、后采集患者外周血。以同期100例体检健康妇女为对照组。比较两组外周血中Th1、Th2细胞比例、Th1/Th2比值、IL-2、IFN-γ、IL-4和IL-10和HMGB1的表达。比较治疗后不同妊娠结局URSA患者细胞因子和HMGB1表达水平。采用Pearson相关分析法分析细胞因子和HMGB1的相关性。结果 URSA治疗前与治疗后和对照组相比、妊娠成功组与失败组相比,IL-2、IFN-γ和HMGB1均升高,IL-4和IL-10均降低（P<0.05）;URSA治疗前与对照组比,Th1细胞比例、Th1/Th2值升高,Th2细胞比例降低（P<0.05）。HMGB1与IL-2和IFN-γ呈正相关,与IL-4和IL-10呈负相关（均P<0.01）。结论 URSA的发病与Th1/Th2细胞平衡向Th1方向偏移有关,HMGB1可能参与了Th1/Th2失衡...     

CCK-8对KLH免疫小鼠脾细胞Th1/Th2平衡的影响

目的： 探讨八肽胆囊收缩素（CCK-8）对Th1/Th2平衡的调节作用。方法: 给予BALB/c小鼠钥孔戚血蓝蛋白（KLH）免疫同时体内给予不同剂量的CCK-8,酶联免疫吸附试验(ELISA)检测其脾细胞培养上清中Th1型细胞因子γ-干扰素(IFN-γ)、白细胞介素-2（IL-2）和Th2型细胞因子白细胞介素-4（IL-4）、白细胞介素-5（IL-5）水平,逆转录聚合酶链式反应(RT-PCR)法检测脾细胞中IFN-γ、IL-2、IL-4、IL-5 mRNA表达;ELISA法检测血清中Th1型抗KLH抗体IgG2a和Th2型抗KLH抗体IgG1水平。结果: ①KLH免疫使小鼠脾细胞分泌Th1/Th2型细胞因子水平明显增高,mRNA表达增高,KLH免疫同时给予CCK-8可使脾细胞培养上清中IFN-γ、IL-2含量进一步增加和IFN-γ、IL-2mRNA表达增高,而使IL-4、IL-5含量降低,IL-4、IL-5 mRNA表达减低和降低IL-4/IFN-γ比值。②KLH免疫小鼠血清中IgG2a、IgG1发生不同程度增高,CCK-8可使其血清中IgG1水平减低而使IgG2a水平增高。结论: CCK-8可促进KLH免疫小鼠体内Th1反应,使Th2优势反应向Th1方向转变。     

中药对溴隐亭致流产大鼠保胎机理的实验研究

目的：探讨补肾益气中药对流产大鼠保胎的作用及其机理。方法：采用孕6、7、8d皮下注射溴隐亭0.125mg/d，诱发SD大鼠流产模型，以放免法测血清PRL、P的动态变化；RT-PCR法测孕12d蜕膜Th1/Th2型细胞因子的表达，观察中药治疗对妊娠结局及以上指标的影响。结果：溴隐亭致流产模型血清PRL、P水平下降，母胎界面Th1/Th2型细胞因子平衡偏向Th1型，补肾益气中药可使其血清PRL及P水平升高，母胎界面Th1/Th2型细胞因子平衡恢复正常。结论：改良溴隐亭致流产模型具备免疫内分泌网络失调的特征，中药可通过对母胎界面免疫内分泌网络的调控维持妊娠。     

Galectin-9对活化的CD4+T细胞免疫调节作用的机制研究

目的 研究Galectin-9对活化的CD4+T细胞的免疫调节作用,并进一步探讨其作用机制.方法 获取野生型C57BL/6小鼠淋巴细胞,利用MACS分选CD4+ na(i)ve T细胞,给予anti-CD3 (2.5 μg/ml)抗体、anti-CD28(5μg/ml)抗体和IL-2(100 ng/ml)刺激,培养3d.将活化的CD4+T细胞分为3组:正常对照组、Galectin-9组和Galectin-9+α-乳糖组.利用CFSE检测T细胞增殖情况,并动态观察细胞形态变化;检测CD4+ CD69+T细胞、Th1、Th2和Th17细胞的比例;并利用ELISA检测淋巴细胞分泌IFN-γ 、IL-4、IL-10、IL-12、IL-17A和TGF-β1等细胞因子的水平;利用Western blot检测T-bet、GATA-3和ROR-yt等T细胞分化调控蛋白的变化.结果 与正常对照组和Galectin-9+α-乳糖组相比,Galectin-9组于2h时开始出现细胞形态改变,同时CD4+ CD69+T细胞、Th1和Th17细胞表达减少(P＜0.05),但Th2细胞无明显变化;培养上清液中IFN-γ、IL-12、IL-17A和TGF-β1的表达水平降低(P＜0.05),而IL-4和IL-10等Th2型细胞因子水平无明显变化;同时T-bet和ROR-γt的表达水平减少(P＜0.05).结论 Galectin-9抑制活化CD4+T细胞的Th1和Th17型免疫应答,而对Th2型免疫应答无影响,免疫调节的机制可能与其在转录水平影响Th1和Th17特定转录因子的表达有关.     

INF—γ／IL—4对早孕期期蜕膜细胞和绒毛滋养层细胞的体外影响

探讨Th1/Th2型细胞因子对人孕早期毛滋养层细胞和蜕膜细胞活性及其内分泌功能的影响。绒毛滋养层细胞和蜕膜细胞活性采用MTT法进行检测。绒毛组织分泌的人绒毛膜促性腺激素（hCG)和蜕膜组织分泌的催乳素（PRL）均采用放免法（RIA）进行分析测定。结果：（1）一定浓范围的Th1型细胞因子TNF－γ（10－1000ng/ml）和Th2型细胞因子IL－4（1－10ng/ml）对绒毛滋养层细胞活性及其hCG分泌分别有不同程度的抑制作用（P＜0．01）和促进作用（P＜0．01）；（2）Th1型细胞因子INF-γ低浓度时（1－10ng/ml）对蜕膜细胞活性及PRL分泌有刺激作用（P＜0．05），高浓度时（100－1000ng/ml）则有抑制作用（P＜0．01），Th2型细胞因子IL-4对蜕膜上述功能的调节作用与对绒毛膜滋养层的调节作用相似。Th1/Th2型细胞因子可能是通过影响绒毛滋养层细胞和蜕膜细胞活性及其内分泌功能而在早期妊娠中起重要的免疫调节作用。     

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.