血管内皮细胞功能相关基因多态性与子痫前期的遗传易感性研究

目的探讨血管内皮细胞功能相关基因即内皮型一氧化氮合成酶(eNOS/NOS3)、血管内皮生长因子(VEGF)、胰岛素样生长因子(IGF1)基因的单核苷酸多态性(SNP)与子痫前期(PE)发病的相关性。方法选取2014年7月至2015年5月于南方医科大学附属深圳妇幼保健院分娩的汉族妇女442例,采用SNapshot技术对eNOS、VEGF、IGF基因5个位点进行检测,分析两组间基因型及等位基因频率的差异。结果 (1)深圳地区汉族妇女中暂未发现存在IGF1基因rs5742620位点、NOS3基因27bp-VNTR in intron 4位点的多态性。(2)PE组NOS3基因rs2070744位点AA基因型、A等位基因频率明显低于对照组(95.5%vs99.3%,P=0.007,OR=0.14,95%CI为0.03-0.73;97.4%vs99.7%,P=0.003,OR=0.13,95%CI为0.028-0.632)。(3)PE与对照组比较,NOS3基因rs1799983位点GG、GT、TT基因型及等位基因分布无显著差异;VEGF基因rs3025039位点GG、AG、AA基因型及等位基因分布无显著差异。结论 (1)NOS3基因rs2070744位点可能与深圳地区汉族妇女PE发生有关。(2)NOS3基因rs2070744位点AA基因型、A等位基因可能是本群体PE发病的保护因素。(3)IGF1基因rs5742620位点、NOS3基因27bp-VNTR in intron 4位点为本群体的罕见突变。     

精神分裂症断裂基因1(DISC1)多态性与精神分裂症的关联研究

目的:探讨精神分裂症断裂基因1(DISC1)与精神分裂症及临床症状的遗传关联.方法:应用病例对照关联研究设计,采用聚合酶链式反应-限制性片断长度多态性(PCR-RFLP)方法:分析466例精神分裂症患者和551例正常对照者DISC1基因2个单核苷酸多态性(SNP)位点与精神分裂症的关联.并采用阳性和阴性症状量表(PANSS)评估患者的临床症状,进一步分析PANSS因子分与DISC1多态性的关联.结果:DISC1基因的两个多态性位点rs821597(等位基因A>G,χ2=6.009,P=0.014;基因型:χ2=6.505,P=0.039)和rs821616(等位基因A>T,χ2=7.063,P=0.008;基因型:χ2=6.928,P=0.031)均与精神分裂症显著关联.由上述2个SNPs组成的多个单体型均与精神分裂症关联[如AT(χ2=7.065,P=0.008,OR=1.42,95%CI=1.10～1.83)和GA(χ2=6.009,P=0.014,OR=0.80,95%CI=0.68～0.96)].上述2个SNPs组成的风险单体型AT间PANSS量表各因子分差异均无统计学意义(均P>0.05).结论:DISC1基因多态性与精神分裂症显著关联,但与精神分裂症症状无关联.     

DTNBP1基因rs4715986位点多态性与中国汉族人群偏执型精神分裂症相关

目的通过两步法研究中国汉族人群DTNBP1基因的多态性与偏执型精神分裂症的相关性。方法发现阶段:在532例偏执型精神分裂症患者及488名健康对照中使用Sanger测序方法检测DTNBP1的11个SNP位点。验证阶段:在1 111例偏执型精神分裂症患者及1 435名健康对照中使用Taqman探针分型的方法对发现阶段检出阳性的rs4715986位点进行验证。结果发现DTNBP1中的rs4715986位点与偏执型精神分裂症的高患病风险相关(χ~2=11.02,P0.01)。在验证人群中重复出rs4715986与偏执型精神分裂症的相关性(χ~2=9.29,P=0.01)。结论DTNBP1基因rs4715986位点的多态性与偏执型精神分裂症的高患病风险相关。DTNBP1可能是中国汉族人群偏执型精神分裂症的易感基因。     

神经丛蛋白A2(PLXNA2)基因多态性与精神分裂症的关联研究

目的:探讨神经丛蛋白(PLXNA2)基因与汉族人群精神分裂症的关联。方法:采用DNA测序检测方法,依据ICD-10诊断标准,在735例汉族精神分裂症住院患者和1316例年龄、性别匹配的正常对照者中,探索PLXNA2基因5个单核苷酸多态性(SNP)位点与精神分裂症的关联。结果:PLXNA2基因的4个SNPs位点与精神分裂症关联(均P<0.05);由rs3811383-rs841865-rs2785622组成的单体型ATT及由rs841865-rs752016组成的单体型AC与精神分裂症关联(均P<0.05)。结论:本研究结果提示PLXNA2基因多态性在中国汉族人群中与精神分裂症关联。     

多巴胺受体D2型基因启动区多态性与精神分裂症关联研究

目的探讨湖北武汉地区汉族人群中多巴胺受体D2型基因(dopamine receptor D2, DRD2)启动区-141位点胞嘧啶插入/缺失多态性与精神分裂症的关联关系.方法应用聚合酶链反应-限制性片段长度多态性方法,对120例精神分裂症患者、100名健康对照者进行基因分型.对精神分裂症患者的 DRD2 -141位点胞嘧啶插入/缺失多态性进行了相关分析.结果 DRD2型基因启动区-141位点的等位基因、基因型频率在精神分裂症组与对照组之间的分布差异有统计学意义(P<0.05).在精神分裂症组中,-141C缺失的等位基因频率为0.11,对照组为0.18(比值比为0.55,95%可信区间为0.30～0.96,P <0.05).结论 -141位点胞嘧啶插入/缺失多态性非独立性地对精神分裂症与 DRD2基因的相关性产生修饰作用.-141位点胞嘧啶缺失可能是湖北武汉汉族精神分裂症患者的保护因素之一.     

男性精神分裂症患者吸烟与多巴胺D_2受体基因多态性的关联研究

目的:探讨多巴胺D_2受体基因(DRD2)多态性与精神分裂症及精神分裂症吸烟行为的关联。方法:选取符合美国精神障碍诊断与统计手册第4版(DSM-IV)精神分裂症诊断标准的男性精神分裂症患者773例(吸烟组567例,非吸烟组206例),男性正常对照302例(吸烟组168例,非吸烟组134例)。选取DRD2的rs1800497和rs1079597单核苷酸多态性(SNP)位点为候选基因位点。采用聚合酶链式反应-限制性片断长度多态性(PCR-RFLP)方法,利用SHEsis遗传分析平台(http:∥analysis.biox.cn/my Analysis.php)分析精神分裂症组与对照组及吸烟与非吸烟候选基因位点基因型与等位基因分布频率。结果:两个SNPs的等位基因和基因型频率分布在精神分裂症组与对照组、精神分裂症的吸烟与非吸烟组、对照组的吸烟与非吸烟组间的差异均无统计学意义(均P0.05);由两个SNPs组成的C-A和T-G单体型在精神分裂症组中的估计频率高于对照组(8.0%vs.5.2%、10.2%vs.4.1%,均P0.05),T-A(34.6%vs 40.2%,P0.05)单体型在精神分裂症组中的估计频率低于对照组;由两个SNPs组成的T-A单体型在正常对照吸烟组中的估计频率低于非吸烟组(2.5%vs.6.1%,P0.05)。结论:DRD2多态性与精神分裂症的易感性可能存在关联,而与精神分裂症患者或正常人吸烟行为的形成可能无关。     

神经型烟碱乙酰胆碱受体α7亚单位基因多态性与精神分裂症的传递不平衡研究

目的 探讨神经型烟碱乙酰胆碱受体α7亚单位基因(neuronal nicotinic acetyleholine receptor α7 subunit gene,CHRNA7)多态性与精神分裂症的关系.方法 应用聚合酶链反应及聚丙烯酰胺凝胶芯片技术检测129个精神分裂症先证者核心家系CHRNA7基因的rs2337980、rs1909884、rs883473三个单核苷酸多态性,并采用基于单倍型的单倍型相对风险检验(haplotype relative risk,HHRR)、传递不平衡检验(transmission disequilibrium test,TDT)及单倍型分析进行统计.结果 (1)HHRR分析结果显示rs2337980位点精神分裂症患者组与虚拟对照组之间等位基因频率差异有统计学意义(P=0.017);(2)TDT分析发现,rs2337980位点与精神分裂症之间可能存在传递不平衡,杂合子父母过多的传递等位基因C给患病子女(P=0.021).(3)单倍型分析发现,rs2337980、rsl909884及rs2337980、rsl909884、rs883473组成的单倍型与精神分裂症有显著相关(总体P=0.034;glohal P=0.027),其中T-C,T-C-T两个单倍型与精神分裂症可能存在传递不平衡.结论 CHRNA7 基因多态性可能与精神分裂症存在关联,rs2337980的变异等位基因T可能是精神分裂症的保护性因子.     

肿瘤坏死因子α和白细胞介素6基因启动子区多态性与精神分裂症的相关性研究

目的 探讨肿瘤坏死因子α(tumor necrosis factorα,TNF-α)基因启动子区-308G/A、-857C/T和-1031T/C位点,白细胞介素6(interleukin-6)基因启动子-174G/C和-572C/G多态性与精神分裂症发生的相关性.方法 采用聚合酶链反应-限制性片段长度多态性分析方法检测346例精神分裂症患者、323名健康对照各个多态性位点的基因型,采用SPSS 13.0进行统计学分析.结果 TNF-α基因-857C/T位点的基因型及等位基因频率分布在精神分裂症组与正常对照组均存在统计学意义(P＜0.05),其中,-857T的等位基因的频率在精神分裂症组均显著高于对照组(x2=9.414,P=0.002,OR=1.511,95%CI:1.160～1.969).-857C/T位点不同基因型患者之间的阳性和阴性症状量表总分及阴性症状差异存在显著性,且TT基因型的分值显著高于CC基因型(P＜0.05).结论 TNF-α基因-857C/T位点可能与精神分裂症的发病存在关联,其中,-857T等位基因可能是易感基因,并且-857C/T位点与阳性和阴性症状量表评分中阴性症状存在关联.     

家族性热性惊厥患儿酪蛋白激酶γ2基因单核苷酸多态性研究

目的　研究酪蛋白激酶γ2 (caseinkinaseⅠ gamma 2 ,CSNK1G2 )基因单核苷酸多态性 (singlenucleotidepolymorphisms ,SNPs)位点与家族性热性惊厥的关系。 方法　通过NCBI的dbSNP数据库选择CSNK1G2基因的 5个单核苷酸多态性位点 ,应用聚合酶链式反应 限制性内切酶片段长度多态性技术 ,检测 5 3例家族性热性惊厥患儿和 10 1名健康对照者的CSNK1G2基因 5个SNPs位点的基因型 ,并使用EH1.2 0程序构建单体型并以单体型为标记进行进一步的患儿和正常人相关分析。结果　 5个SNPs位点的基因型频率在惊厥患儿和正常人群中分布均符合Hardy Weinberg平衡。其中 3个位点SNPrs740 42 3、rs2 2 7773 7、rs10 5 9684的基因型频率和基因频率在家族性热性惊厥患儿和对照组分布差异有显著性 (P <0 .0 5 ) ,1个位点rs2 0 74882基因型频率和基因频率在两组人群中分布差异无显著性 (P >0 .0 5 ) ,另一位点rs480 682 5因基因频率较低 ,故未作统计。结论　CSNK1G2基因SNPsrs740 42 3、rs2 2 7773 7、rs10 5 9684可能与家族性热性惊厥相关。     

ESR1基因单核苷酸多态性及单倍型与精神分裂症的关联研究

目的 探索雌激素受体1 (estrogen receptor 1,ESR1)基因rs2234693、rs9340799和rs3798759位点单核苷酸多念性(single nucleotide polymorphisms,SNPs)及其单倍型与精神分裂症(schizophrenia,SZ)发病之间的相关性.方法 应用聚合酶链反应-限制性片段长度多态性技术对333例SZ患者和315名正常对照rs2234693、rs9340799和rs3798759位点进行基因分型,应用x2检验对SZ组和对照组等位基因、基因型和单倍型频率进行分析.结果 rs2234693、rs9340799位点两组间基因型频率及等位基因分布差异均无统计学意义(P＞0.05).SZ组rs3798759位点GG基因型频率及G等位基因频率均高于健康对照组(P＜0.01).性别分层分析提示,女性SZ患者rs3798759位点TG、GG基因型频率及G等位基因频率均高于健康女性(P＜0.05).单倍型C-A-G和C-G-G在SZ组的分布频率高于对照组(P＜0.05).结论 rs3798759位点突变可能为女性精神分裂症发生的风险因子,C-A-G和C-G-G单倍型可能为精神分裂症的遗传风险单倍型.     

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.