红细胞补体受体1单核苷酸多态性与骨关节结核易感性的关联研究

目的探讨红细胞补体受体1(CR1)单核苷酸多态性(SNP)与骨关节结核(bone and joint tuberculosis)发病的关系。方法收集110例骨关节结核患者(实验组)和104例健康体检者(对照组)的外周血样本,采用单碱基延伸的PCR技术和DNA测序方法对CR1基因3个SNP位点(rs11118167C/T、rs2274567G/A、rs4844600G/A)进行多态性检测,分析2组CR1表达水平、2组CR1基因各SNP位点基因型对于CR1水平差异、CR1基因各SNP位点基因型、等位基因的分布差异及其与骨关节结核患病风险的关系。结果 2组rs4844600G/A基因型和等位基因分布的差异有统计学意义(P0.05)。CR1基因rs4844600G/A位点GG基因型携带者患骨关节结核的风险为非携带者的2.262倍(95%CI:1.275~4.013),其等位基因G携带者患病风险为非携带者的1.565倍(95%CI:1.058~2.314)。rs11118167C/T、rs2274567G/A这2个SNP位点与骨关节结核的患病风险无关(P0.05)。健康对照组CR1的平均荧光前强度为50.87±14.526,高于骨关节结核组的38.95±12.794,差异有统计学意义(t=-6.379,P0.001)。骨关节结核组中,CR1基因rs11118167 C/T、rs2274567 G/A和rs4844600 G/A位点多态性与骨关节结核患者红细胞CR1水平无关(P0.05)。健康对照组中,rs11118167 C/T位点CC、CT基因型携带者的红细胞CR1水平低于TT基因型者;rs2274567G/A位点GG、GA基因型携带者的CR1水平低于AA基因型者(P0.05)。结论骨关节结核患者红细胞免疫功能降低,CR1基因rs4844600G/A位点与骨关节结核发病相关,CR1基因rs4844600G/A位点GG基因型与骨关节结核患者CR1水平低无关。     

IL-6634C/G基因多态性与子宫内膜异位症易感性的相关研究

目的 探讨中国南方汉族妇女白细胞介素-6(interleukin-6,IL-6)基因启动子区634C/G (rs1800796)位点单核苷酸多态性(single nucleotide polymorphism,SNP)与子宫内膜异位症(endometriosis,Ems)遗传易感性的相关性.方法 收集经手术证实的432例Ems患者和499名对照人群外周血,采用荧光定量PCR为基础的高分辨率熔解曲线分析(high resolution melting,HRM)技术检测IL-6 634C/G基因SNP.结果 IL-6 634C/G位点等位基因、携带等位基因G及其基因型的分布在Ems组和对照组间差异均有统计学意义(P=0.032、0.014和0.045),其中等位基因C使Ems发病风险提高1.057倍,而等位基因G使其降低0.835倍;携带等位基因G使Ems发病风险降低0.822倍,而不携带使其提高1.143倍;CG与CC基因型相比患Ems的危险度低0.704倍(95％CI:0.533～0.931).但IL-6 634C/G位点携带等位基因C的分布在两组间差异无统计学意义(P=0.729).结论 中国南方汉族妇女IL-6 634C/G位点SNP与Ems遗传易感性存在相关性.     

子宫内膜异位症与细胞色素P450 1A1基因A4889G突变的相关性

目的探讨细胞色素P450 1A1(cytochrome P450 1A1,CYP1A1)基因A4889G突变与子宫内膜异位症(endometriosis,EM)的遗传易感性的关系.方法采用等位基因特异性聚合酶链反应的方法,研究了76例EM患者和80名正常对照CYP1A1基因A4889G位点碱基突变.两组均为广东籍汉族妇女.结果 CYP1A1基因A4889G位点等位基因A、G在EM组和对照组分布的差异有显著性(χ2=7.498,P<0.01),其中等位基因G使患EM的相对危险度提高了1.957倍.CYP1A1基因A4889G位点各基因型分布在两组间差异有显著性(χ2=6.915,P<0.05),GG基因型与AA基因型相比患EM的危险度高3.437倍(χ2=5.430,P<0.05).结论 CYP1A1基因A4889G突变等位基因与EM有一定的关联,突变基因型增加了EM的发病风险.     

中国甘肃汉/ 回族人群C1GALT1、DEFA 基因多态性与IgA 肾病易感性的关系

目的:探讨β-1,3鄄半乳糖基转移酶(C1GALT1)基因rs1008898 位点及琢防御素(α-defensin,DEFA) 基因rs2738081 位点多态性与中国甘肃省汉族人群和回族人群IgA 肾病易感性的关系,筛查预测IgA 肾病的分子标记。方法:本研究选取甘肃地区患IgA 肾病的汉族个体146 例、回族个体83 例作为实验组,另选取健康汉族个体180 例、健康回族个体100例作为对照组。采用聚合酶链反应鄄限制性片段长度多态性(Polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP) 方法以及PCR 产物基因测序法对单核苷酸多态性基因位点进行基因分型,采用卡方检验比较各基因型、等位基因在病例组和对照组中的分布差异,评价各基因型、等位基因与IgA 肾病发病风险的关系。结果: 汉族IgA 肾病患者rs1008898 位点的GG 基因型频率与健康对照组之间有统计学差异(OR=2.489,95CI:1.259 ~4.922,字2 =7.037,P =0.008),且G 等位基因可能增加患IgA 肾病的风险(OR = 1.268,95% CI:1.056 ~ 1.523,字2 = 6.709,P = 0.01)。回族IgA 肾病患者rs1008898 位点的多态性与健康对照组之间差异无统计学意义(P>0.05)。(3)rs2738081 位点多态性在汉族、回族IgA 肾病患者及其健康对照组之间的分布差异无统计学意义(P>0.05)。结论:rs1008898 位点G 等位基因可能增加甘肃地区汉族人群患IgA 肾病的风险。     

CDKAL1基因rs4712523多态性与内蒙古地区汉族人群2型糖尿病相关

目的 研究内蒙古地区汉族人群CDKAL1基因rs4712523单核苷酸多态性(SNP)的等位基因和基因型频率分布与2型糖尿病(T2DM)的相关性.方法 采用等位基因特异性聚合酶链式反应(AS-PCR),对382例内蒙古地区汉族人(其中T2DM组192例,对照组190例)rs4712523进行基因分型.结果 T2DM组中rs4712523的G等位基因频率和GG基因型频率分别为47.4％和6.3％,均显著高于对照组的35.3％和3.2％(P＜0.05).G等位基因携带者患T2DM的风险是A等位基因的1.654倍(OR=1.654,95％ CI=1.237-2.212).结论 CDKAL1基因rs4712523多态性位点的G等位基因可能是内蒙古地区汉族人T2 DM的易感基因之一.     

福建汉族胰岛素样生长因子受体基因多态性与非小细胞肺癌易感性的关联研究

目的 探讨胰岛素样生长因子受体(insulin-like growth factor receptor,1GF-1R和IGF-2R)基因多态性与福建汉族人非小细胞肺癌(non-small-cell lung cancer,NSCLC)易感性的关系.方法 采用病例-对照研究,用聚合酶链反应-限制性片段长度多态性和DNA测序法检测福建籍汉族健康人258名和NSCLC患者260例的IGF-IR +1013和IGF-2R+1619两个位点的等位基因分布,探讨不同基因型与NSCLC发病的相关性.结果 (1) IGF-1R +1013(G/A)位点基因型和各等位基因的频率在两组中分布差异有统计学意义(P＜0.05).对于IGF-1R+ 1013(G/A)位点,与GG基因型者相比,GA基因型者NSCLC患病风险增加0.80倍(95％ CI:1.24～2.59,P=0.002),AA基因型者的风险增加2.59倍(95％ CI:1.78～7.26,P=0.000),而等位基因A携带者(GA+AA基因型)患病风险增加0.98倍(95％ CI:1.39～2.83,P=0.000).未发现IGF-2R +1619(G/A)位点各基因型和等位基因的频率分布在两组中差异有统计学意义(P＞0.05).(2)根据病理类型分层分析发现IGF-1R +1013(G/A)变异等位基因A携带者(GA+AA)患肺鳞癌的风险增加2.20倍(95％ CI:1.75～5.84,P=0.000),患肺腺癌的风险增加0.55倍(95％Ch l.00～2.41,P=0.049),患其他类型肺癌的风险增加0.96倍(95％CI:1.10～3.49,P=0.023).未发现两基因多态性与临床分期、淋巴结转移、远处转移有关(P＞0.05).(3)联合分析发现,IGF-1R+1013(G/A)和IGF-2R +1619(G/A)基因联合多态性与NSCLC的患病风险存在相关性(P=0.003).结论 IGF-IR+ 1013(G/A)位点变异等位基因A是肺癌发生的风险因素,IGF-1R+1013(G/A)和IGF-2R+1619(G/A)基因多态性对肺癌的发生有协同作用.     

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.     

IL-23R基因多态性与吉林人群强直性脊柱炎易感性的关联研究

目的:探讨吉林人群IL-23R基因rs7517847和rs10489629位点的单核苷酸多态性与强直性脊柱炎易感性的关系。方法:采用PCR-RFLP方法对188例强直性脊柱炎患者进行IL-23R基因多态性检测,与100例健康者对照分析。结果:两个SNP位点(rs7517847和rs10489629)各基因型频率和等位基因频率在AS组与对照组之间的分布差异均有统计学意义(P0.05),并在假设遗传方式下,rs7517847位点的纯合突变GG基因型与(TG+TT)基因型比较;rs10489629位点的纯合突变AA基因型与(GA+GG)基因型比较,其频率分布差异在AS组与对照组之间也具有统计学意义(P0.05)。结论:IL-23R基因rs7517847和rs10489629位点的多态性均与吉林人群AS易感性有关;携带G等位基因(或A等位基因)且为GG(或AA)基因型的个体患AS的倾向性增大,可能是患AS的易感因素之一。     

基质金属蛋白酶-3基因多态性与脑卒中亚型的相关性

目的 探讨中国北方汉族人群基质金属蛋白酶-3(matrix metalloproteinase-3,MMP-3)基因多态性与缺血性脑卒中(ischemic stroke,IS)亚型的相关性.方法 应用病例对照研究,选取289例急性缺血性脑卒中患者(发病≤3d)和175名同期健康体检者.卒中组按急性卒中治疗低分子肝素试验病因分型法分为大动脉粥样硬化性(large artery atherosclerotic,LAA)脑卒中185例,小动脉闭塞性(small artery occlusion,SAO)脑卒中104例.选取MMP-3基因rs3025058(-11715A/6A),rs522616(-709A/G)及rs679620(133A/G)3个常见单核苷酸多态性(single nucleotide polymorphisms,SNPs)位点,应用聚合酶链反应限制性片段长度多态性或直接测序法对MMP-3基因3个SNP位点进行基因分型.结果 3个位点存在不完全连锁不平衡,且基因多态性均与LAA型脑卒中相关(P＜0.05).在显性模型中,rs3025058位点5A5A+5A6A基因型携带者患LAA型脑卒中的风险是6A6A基因型携带者的1.72倍(P=0.017,OR=1.72,95％CI:1.10～2.69);rs522616位点GG+ AG基因型携带者患LAA型脑卒中的风险是AA基因型携带者的0.52倍(P=0.005,OR=0.52,95％CI:0.33～0.82);rs679620位点AA+ GA基因型携带者患LAA型脑卒中的风险是AA基因型携带者的1.55倍(P=0.042,OR=1.55,95％CI:1.01～2.37).但是,3个SNPs基因型和等位基因频率在对照组与SAO型脑卒中之间差异无统计学意义(P＞0.05).另外,LAA组5A-A-A及6A-A-A单倍型高于对照组,差异有统计学意义(P＜0.05),而6A-G-G单倍型显著低于对照组(P＜0.01).结论 MMP-3血清水平在LAA型脑卒中急性期增高明显,SAO型脑卒中次之;中国北方汉族人群MMP-3基因rs3025058,rs522616及rs679620多态性可能与LAA型脑卒中易感性相关.     

中国甘肃汉/回族人群C1GALT1、DEFA基因多态性与IgA肾病易感性的关系北大核心CSCD

目的:探讨β-1,3-半乳糖基转移酶(C1GALT1)基因rs1008898位点及α防御素(α-defensin,DEFA)基因rs2738081位点多态性与中国甘肃省汉族人群和回族人群Ig A肾病易感性的关系,筛查预测Ig A肾病的分子标记。方法:本研究选取甘肃地区患Ig A肾病的汉族个体146例、回族个体83例作为实验组,另选取健康汉族个体180例、健康回族个体100例作为对照组。采用聚合酶链反应-限制性片段长度多态性(Polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP)方法以及PCR产物基因测序法对单核苷酸多态性基因位点进行基因分型,采用卡方检验比较各基因型、等位基因在病例组和对照组中的分布差异,评价各基因型、等位基因与Ig A肾病发病风险的关系。结果:(1)汉族Ig A肾病患者rs1008898位点的GG基因型频率与健康对照组之间有统计学差异(OR=2.489,95CI:1.259~4.922,χ~2=7.037,P=0.008),且G等位基因可能增加患Ig A肾病的风险(OR=1.268,95%CI:1.056~1.523,χ~2=6.709,P=0.01)。(2)回族Ig A肾病患者rs1008898位点的多态性与健康对照组之间差异无统计学意义(P>0.05)。(3)rs2738081位点多态性在汉族、回族Ig A肾病患者及其健康对照组之间的分布差异无统计学意义(P>0.05)。结论:rs1008898位点G等位基因可能增加甘肃地区汉族人群患Ig A肾病的风险。     

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.