瘦素、脂联素与TNF-α在子痫前期胎盘中的表达及相关性研究

目的检测子痫前期胎盘中瘦素、脂联素及TNF-α的表达并探讨TNF-α与另两个因子的相关性。方法采用免疫组化方法检测55例子痫前期患者及21例正常对照组胎盘瘦素、脂联素及TNF-α的表达水平。结果重度子痫前期组胎盘瘦素表达水平显著高于正常组(P<0.01),轻度组与正常组无统计学差异(P>0.05);重度组胎盘脂联素表达水平显著低于正常组(P<0.01),轻度组与正常组无统计学差异(P>0.05);子痫前期胎盘TNF-α表达水平显著高于正常组(P<0.05及P<0.01);重度组瘦素与TNF-α成正相关(r=0.536),而正常组与病例组中脂联素与TNF-α均无相关性(r=0.416r、=0.398及r=0.254)。结论脂联素、瘦素及TNF-α参与子痫前期的发病,且TNF-α可调节瘦素的水平,但对脂联素的调节不明显。     

IL-21、IL-22在子痫前期患者胎盘组织中的表达水平及意义

目的通过研究子痫前期患者与正常孕妇胎盘组织中白介素-21(IL-21)和白介素-22(IL-22)的水平,探讨IL-21和IL-22在子痫前期发生机制中的作用。方法采用酶联免疫吸附法(ELISA)分别测定轻度、重度子痫前期患者和正常孕妇胎盘组织中IL-21和IL-22的水平,比较3组间细胞因子的表达水平。结果通过比较发现,轻度、重度子痫前期组IL-21、IL-22在胎盘组织中的表达与对照组比较,差异有统计学意义(P0.05)。但是,虽然重度子痫前期组IL-21、IL-22在胎盘组织中的表达均高于轻度子痫前期组,但是差异无统计学意义(P0.05)。结论子痫前期组患者胎盘组织中IL-21、IL-22的表达增强可能与子痫前期的发生、发展有关。     

IL-2、IL-10、TNF-α在子痫前期不同发病类型中的水平变化及意义

目的探讨IL-2、IL-10、TNF-α在子痫前期不同发病类型患者血清中的水平变化。方法用ELASA检测30例早发型重度子痫前期、30例晚发型重度子痫前期和30例正常妊娠孕妇血清中IL-2、IL-10、TNF-α的水平。结果早发型重度子痫组和晚发型子痫前期组患者体内IL-2、TNF-α水平与对照组相比明显升高,差异有显著统计学差异(P0.05),早发型重度子痫组和晚发型子痫前期组中IL-2、IFN-α水平相比也有显著统计学差异(P0.05);早发型重度子痫组和晚发型子痫前期组患者体内IL-10水平与对照组相比明显降低差异有统计学意义(P0.05),而早发型重度子痫组和晚发型子痫前期组患者体内IL-10水平相比差异无统计学意义(P0.05)。结论子痫前期患者血清中的IL-2、TNF-α的水平升高及IL-10水平降低与该病的发生发展密切相关。     

子痫前期患者胎盘组织TNF-α及Caspase-3的表达及相关性研究

目的探讨TNF-α及Caspase-3在子痫前期患者胎盘组织中的表达及相关性。方法采用SP法对轻、重度子痫前期组40例和正常妊娠组20例的胎盘组织进行TNF-α和Caspase-3的免疫组化染色,观察各组TNF-α和Caspase -3的定位、分布和表达量的差异。结果重度子痫前期组的TNF-α及Caspase-3的表达量较正常组显著升高(P< 0．01)。另外,重子痫前期度组TNF-α与Caspase-3的表达量呈正相关(R=0．698,P<0．001)。结论子痫前期时胎盘可能是TNF-α的来源之一。子痫前期的发病可能与胎盘局部产生的TNF-α诱导的滋养细胞凋亡(Caspase-3是凋亡通路下游关键蛋白酶)增加有关。     

Th17细胞在子痫前期患者外周血表达增加

观察正常妊娠妇女和子痫前期疾病患者外周血CD4+T细胞中Th17细胞和特异性转录因子维A酸相关孤独受体(retinoid-related orphan nuclear receptor,RORγt)的表达和意义。实验组为子痫前期疾病患者25例,正常妊娠妇女20例,未孕妇女20例。采集研究对象外周血,酶联免疫吸附试验(ELISA)检测Th17细胞相关细胞因子IL-17A,IL-6,TNF-α的表达,Ficoll法分离外周血单个核细胞(PBMC),免疫磁珠分选CD4+T淋巴细胞,逆转录-聚合酶联反应(RT-RCR)半定量检测CD4+T细胞中Th17细胞特异性转录因子RORγt的表达,流式细胞术检测CD4+IL-17+T细胞比例。子痫前期患者外周血清中IL-6、IL-17A的含量分别为(31.72±13.34)ng/L、(2.61±1.64)ng/L,高于正常妊娠组水平,差异有显著统计学意义(P<0.01),TNF-α在子二组间的表达分别为(18.00±8.64)ng/L和(11.69±3.68)ng/L,差异有统计学意义(P<0.05);RORγt mRNA在子痫前期组的表达高于正常妊娠组,净光密度值差异有显著统计学差异(P<0.01),CD4+IL-17+T细胞在子痫前期组的表达为(1.83±0.42)%,高于正常妊娠组(0.87±0.26)%,差异有显著统计学意义(P<0.01)。子痫前期患者外周血CD4+T细胞中RORγt mRNA、Th17细胞以及Th17细胞相关细胞因子表达异常,可能在疾病的发病机理中起到重要作用。     

CD39分子在子痫前期患者外周血CD4+T细胞及脐静脉内皮细胞的表达及临床意义北大核心CSCD

目的：探讨CD39分子在子痫前期患者外周血CD4+T细胞、Treg、Foxp3-CD4+T细胞及脐静脉内皮细胞的表达及临床意义。方法：采集59例正常妊娠者、23例妊娠期高血压患者及65例子痫前患者(包括28例轻度子痫前期患者和37例重度子痫前期患者)外周血，流式细胞技术检测各组妊娠妇女外周血CD4+T细胞、Treg(Foxp3+CD4+T细胞)、Foxp3-CD4+T细胞比例及CD39分子表达率。随机获取胎儿分娩后的脐带(正常妊娠组18例、重度子痫前期组20例)，检测脐静脉血管内壁细胞CD31+CD39+内皮细胞群比例。结果：正常妊娠组、妊娠期高血压组、子痫前期组3组母体外周血CD4+T细胞比例[(33.71±9.80)%vs (29.59±14.22)%vs (29.63±11.11)%]及CD39表达率[2.84(0.89～5.51) vs 2.50(0.89～4.19) vs 1.39(0.79～3.51)]差异无统计学意义(P>0.05)。正常妊娠组Treg比例及CD39表达率明显高于子痫前期组[3.25(1.39～4.53) vs 1.63(1.01～2.58);33.90(22.80～59.40) vs 21.20(16.70～32.55),P<0.001]；正常妊娠组Foxp3-CD4+T细胞比例明显低于子痫前期组[94.40(93.00～96.10) vs 95.60(94.10～97.40),P=0.016]，但3组CD39表达率差异无统计学意义[1.80(0.55～4.49) vs 1.92(0.54～3.60) vs 0.92(0.49～3.24),P=0.340]。轻度子痫前期组与重度子痫前期组外周血CD4+T细胞[(32.35±10.51)%vs (27.56±11.24)%]、Treg[1.80(0.93～2.58) vs 1.44(1.03～2.58)]、Foxp3-CD4+T细胞[95.6(94.5～97.1) vs 95.6(94.0～97.6]比例差异无统计学意义(P>0.05)；轻度子痫前期组CD4+T细胞、Treg、Foxp3-CD4+T细胞CD39表达率均明显高于重度子痫前期组[2.08(1.20～5.05) vs 0.95(0.68～1.78);26.20(19.55～58.55) vs 17.60(13.90～23.15);2.14(0.78～3.69) vs 0.62(0.40～1.73),P<0.05]。重度子痫前期患者脐静脉血管内壁细胞CD31+CD39+内皮细胞群比例明显低于正常妊娠组[6.32(3.27～10.55) vs 18.95(9.90～27.48),P=0.020]。结论：母体外周血发挥免疫抑制功能的Treg数量及CD39分子表达减少可能参与子痫前期发生发展；重度子痫前期患者脐静脉血管内壁细胞CD31+CD39+内皮细胞群较正常妊娠者明显减少，可能与血管内皮损伤机制有关。     

妊娠期高血压疾病患者外周血中Th22/Th17/Th1细胞变化及临床意义

目的:分析妊娠期高血压疾病(HDP)患者外周血中Th22、Th17和Th1细胞及相关细胞因子水平的变化,探讨促炎性CD4+T细胞在疾病演变过程中的作用。方法:选择妊娠期高血压疾病患者90例,其中妊娠期高血压及轻、重度子痫前期(PE)患者各30例作为实验组,另选择同期正常妊娠孕产妇30例作为对照组。采用流式细胞技术检测Th22、Th17和Th1细胞的比例,通过ELISA法测定外周血中IFN-γ、TNF-α、IL-6、IL-17和IL-22的浓度。结果:妊娠期高血压组中患者外周血Th1细胞及IFN-γ水平明显高于正常妊娠组(P0. 05),且二者水平呈正相关(P0. 05);轻度子痫前期组中Th17细胞及IL-6、IL-17和IL-22水平与妊娠期高血压组比较差异具有统计学意义(P0. 05),且Th17细胞比例与IL-6、IL-17含量均呈正相关(P0. 05);重度子痫前期组Th22/Th17/Th1细胞及相关细胞因子水平均明显高于其他各妊娠组(P0. 05),且TNF-α、IL-6和IL-22含量均与Th22细胞比例呈正相关(P0. 05);重度早发型PE组TNF-α和IL-22水平均高于晚发型PE组(P0. 05)。结论:促炎性CD4+T细胞及相关细胞因子协调作用,共同加重炎症反应,可能是妊娠期高血压疾病发生、发展的重要因素。孕妇外周血中Th22/Th17/Th1细胞水平的异常变化与HDP的病情密切相关,有望成为联合诊断的重要指标。     

新型冠状病毒2型感染儿童后外周血淋巴细胞亚群和血清细胞因子水平变化分析

目的分析儿童新型冠状病毒2型(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)感染后外周血淋巴细胞亚群和血清细胞因子水平变化。方法采集12例SARS-CoV-2感染儿童急性期(病程第1周内且咽拭子SARS-CoV-2核酸检测阳性)和恢复期(病程2周以上且咽拭子病毒核酸检测阴性)外周血,应用流式细胞术检测淋巴细胞亚群和血清细胞因子(IFN-γ、IL-1β、IL-2、IL-4、IL-5、IL-6、IL-8、IL-10、IL-12p70、IL-17A、IL-17F、IL-22、TNF-α、TNF-β)表达。同期健康体检儿童作为对照组。结果 12例SARS-CoV-2感染患儿根据临床分型包括无症状感染6例,轻型3例,普通型3例,无重症及危重症患者。感染后急性期CD4+/CD8+低于对照组(P=0.004),淋巴细胞中CD19+B细胞比例高于对照组(P=0.038);感染后恢复期,淋巴细胞中CD3+CD4+T淋巴细胞比例低于对照组(P=0.027),CD3+CD8+T淋巴细胞比例高于对照组(P=0.037),CD4+/CD8+进一步降低,低于急性期(P=0.042);淋巴细胞中CD19+B细胞比例和细胞计数均高于对照组(P值分别为0.002、0.026)。感染后急性期和恢复期细胞因子IL-17A、IL-17F、IL-2、IL-22均高于对照组(P0.05),IL-4、IL-5和TNF-α则在恢复期高于对照组(P0.05),其中IL-5在恢复期高于急性期(P=0.026)。结论 CD19+B淋巴细胞和CD3+CD8+T淋巴细胞以及由Th17和Th2细胞分泌的细胞因子参与了儿童非重症SARS-CoV-2感染的抗病毒免疫应答过程。动态监测儿童患者的免疫功能变化,对于判断患者的病情有较好的参考价值。     

瘦素、脂联素与TNF-α在子痫前期患者血清中的表达及相关性研究

目的检测子痫前期患者血清瘦素、脂联素及TNF-α的表达并探讨TNF-α与瘦素、脂联素的相关性。方法采用酶联免疫吸附法(ELISA)检测44例子痫前期患者及24例正常孕妇血清中瘦素、脂联素及TNF-α的表达水平。结果(1)轻、重度子痫前期患者血清瘦素水平分别为4308.60±378.83pg/ml、4476.39±115.18pg/ml,明显高于对照组4041.97±455.39pg/ml,差异有统计学意义(P<0.05,P<0.01);(2)轻度、重度子痫前期患者血清TNF-α水平分别为73.33±57.91pg/ml及538.50±551.25pg/ml,明显高于对照组62.89±82.85pg/ml,而血清脂联素水平分别为8.06±5.06pg/ml、5.28±1.47pg/ml,明显低于对照组12.73±2.90pg/ml,重度组与对照组之间的差异有统计学意义(P<0.05);(3)重度组瘦素与TNF-α成正相关(r=0.478),脂联素与TNF-α成负相关(r=-0.536),轻度组及对照组中TNF-α与瘦素、脂联素均无相关性。结论瘦素、脂联素及TNF-α参与子痫前期的发病,且TNF-α可以调节瘦素及脂联素的水平。     

KiSS-1在子痫前期患者胎盘组织中的表达及意义

目的探讨肿瘤转移抑制基因KiSS-1是否是子痫前期的发病机制。方法采用免疫组化SP法检测25例正常足月妊娠妇女(正常妊娠组)与40例子痫前期患者(子痫前期组,其中轻度子痫前期15例、重度子痫前期25例)胎盘组织中KiSS-1的表达。结果KiSS-1主要位于胎盘绒毛小叶的合体滋养细胞。子痫前期组胎盘组织中KiSS-1的平均光密度为(0.137±0.010),其中轻度子痫前期为(0.132±0.004),重度子痫前期为(0.140±0.012);均明显高于正常妊娠组的(0.124±0.010),P值分别为P<0.01、P<0.05(P=0.019)、P<0.01。结论胎盘组织中KiSS-1的表达水平随病情程度的加重而增高,可能与子痫前期的发病有关。     

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.     

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.     

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.     

The case for allele‐specific recognition by the TCR

There is a sharp difference in how one views TCR structure–function–behaviour dependent on whether its recognition of major histocompatibility complex‐encoded restriction elements (R) is germline selected or somatically generated. The generally accepted or Standard model is built on the assumption that recognition of R is by the V regions of the αβ TCR, which is not driven by allele specificity, whereas the competing model posits that recognition of R is allele‐specific. The establishing of allele‐specific recognition of R by the TCR would rule out the Standard model and clear the road to a consideration of a competing construct, the Tritope model. Here, the case for allele‐specific recognition (germline selected) is detailed making it obvious that the Standard model is untenable.     

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.