钠离子转运基因多态性及血清Na~+水平与朝鲜族女性原发性高血压相关性研究

目的探讨rs11643718、rs7187932、rs12447134和rs3743966位点多态性与血清Na~+与朝鲜族女性原发性高血压的相关性。方法对116例朝鲜族原发性高血压和109名朝鲜族健康者进行研究,运用LDR连接酶技术检测分析4个SNP位点多态性,全自动生化分析仪检测血清Na~+。结果朝鲜族女性原发性高血压组和正常对照组之间rs11643718高血压组和正常对照组GG基因型与GA和AA基因型频率及G,A等位基因频率分布差异有统计学意义(P0.01)。rs7187932、rs3743966位点高血压组和正常对照组基因型频率等位基因频率分布差异均无统计学意义(P0.05)。朝鲜族女性原发性高血压组和正常对照组之间血清Na~+水平差异无统计学意义(P0.05),而rs7187932位点对照组GG基因型组与高血压组GG基因型组及对照组GA+AA组血清比较Na~+水平差异有统计学意义(P0.05)。结论 rs11643718位点等位基因A是朝鲜族女性高血压的危险因素。rs7187932位点GG基因型组与血清钠离子水平正相关。     

P53(rs1042522)基因多态性与子宫内膜异位症易感性的相关研究

目的 探讨肿瘤抑制基因P53 (tumor suppressor gene,P53)多态性与子宫内膜异位症(endometriosis,EM)遗传易感性的相关性.方法 应用等位基因特异性PCR技术结合DNA测序的方法对460例EM患者、650例无EM妇女(对照组)及113例子宫内膜癌患者的P53基因rs1042522位点(G/C)多态性进行分析.结果 各组均存在P53 (rs1042522) G/C多态性,且P53 (rs1042522)位点等位基因及基因型的分布在EM组与对照组之间差异有统计学意义(P值均小于0.01),其中等位基因C使EM发病风险提高1.179倍,等位基因G使其风险降低0.854倍；GC与GG基因型相比患EM的危险度增高1.548倍(95％CI为1.153～2.081),CC与GG基因型相比患EM的危险度增高1.865倍(95％CI为1.326～2.625).P53 (rs1042522)位点等位基因及基因型的分布在子宫内膜癌组与对照组之间差异有统计学意义(P值均小于0.01),且等位基因C使内膜癌发病风险提高1.278倍,而等位基因G使其风险降低0.772倍；GC与GG基因型相比患内膜癌的危险度增高2.074倍(95％CI为1.197～3.599),CC与GG基因型相比患内膜癌的危险度增高2.864倍(95％CI为1.557～5.263).P53 (rs1042522)位点等位基因及基因型的分布在EM组与子宫内膜癌组之间差异无统计学意义.结论 P53基因rs1042522位点(G/C)的单核苷酸多态性与EM遗传易感性存在相关性,且从遗传学角度分析,EM的发病机制可能更类似于肿瘤.     

GALNT2 rs4846914多态性位点在中国汉族人群分布及其对血脂的影响

目的 研究多肽N-乙酰半乳糖胺基转移酶2(N-acetylgalactosaminyltransferase 2,GALNT2)基因rs4846914位点在中国汉族人群中的分布频率,分析该位点对血脂水平和血脂异常的影响.方法 采用横断面调查方法,收集2397例(其中男性1511例,女性886例)汉族人群样本.采用MALDI-TOF MS技术检测rs4846914位点基因分型,采用多重线性回归法分析基因型对4项血脂指标影响程度的大小,二分类Logistic回归法分析基因型对血脂异常发病风险的大小,以P＜0.05为有统计学意义.结果 GALNT2 rs4846914位点A等位基因在中国汉族人群中的频率为20.4％.AA基因型人群的高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)水平显著高于GG基因型(P=0.034),女性人群AA基因型的总胆固醇(total cholesterol,TC)水平也显著高于GG型(P=0.019).在男性人群,AA基因型的低HDL-C血症发病风险是GG基因型的0.478倍.(P=0.045,OR=0.478,95％ CI:0.233-0.983).结论 中国汉族人群rs4846914位点以G等位基因为主,明显不同于西方人群以A等位基因为主的特点.中国汉族人群中,该位点AA基因型可增加血浆HDL-C水平,并减少男性低HDL-C血症发生.     

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.     

内皮固有型一氧化氮合酶基因单核苷酸多态性与冠心病的相关性研究

探讨内皮固有型一氧化氮合酶(ecNOS)基因的单核苷酸多态性(SNP)与冠心病(CAD)的相关性.提取107例CAD患者和132名健康对照者外周血有核细胞DNA,应用荧光标记单碱基延伸分型技术及寡核苷酸微阵列芯片杂交技术检测ecNOS基因的2个标签SNP(tag SNP)rs7830和rs3918188.结果发现CAD组rs7830的CC基因型频率和C等位基因频率明显低于健康对照组(P＜0.05).两组rs3918188的基因型频率及等位基因频率无统计学差异(P＞0.05).通过对2个SNP进行单倍型分析发现,CAD组和健康对照组的单倍型频率具有统计学差异(P<0.05).结果提示ecNOS基因 rs7830多态性变异及由rs7830和rs3918188构建的CA、AA单倍型是CAD的遗传危险因素.     

新生儿支气管肺发育不良TLR-10、SP-A1基因多态性及其与病情程度的关系

目的 探讨新生儿支气管肺发育不良（BPD）患儿Toll样受体10(TLR-10)、肺泡表面活性物质蛋白A1(SP-A1)基因多态性及其与病情程度的关系。方法 选取承德市中心医院83例BPD患儿作为观察组,另选取83例同期健康新生儿作为对照组。比较两组血清TLR-10、SP-A1水平、TLR-10rs11096955位点、SP-A1AA50位点基因多态性,分析两者基因多态性对BPD易感性的影响及与病情程度的关系。结果 观察组血清TLR-10、SP-A1水平高于对照组（P<0.05）;TLR-10 rs11096955位点、SP-A1 AA50位点基因型分布具有人群代表性。观察组与对照组TLR-10 rs11096955位点、SP-A1 AA50位点基因型、等位基因频率差异有统计学意义（P<0.05）;TLR-10 rs11096955位点AA基因型BPD易感性是AC/CC的1.401倍;SP-A1 AA50位点GG基因型BPD易感性是GC/CC的1.692倍;TLR-10 rs11096955位点AA基因型、等位基因A频率、SP-A1 AA50位点GG基因型、等位基因G频率与...     

CTLA4基因与Ⅰ型糖尿病易感性的关联研究

目的探讨细胞毒性T淋巴细胞相关抗原4(CTLA4)基因单核苷酸多态性位点rs231775(G/A)与Ⅰ型糖尿病(TIDM)易感性的关系。方法采用病例对照研究,收集TIDM患者及正常儿童外周血,提取基因组DNA,应用PCR扩增产物直接测序法对多态性位点rs231775进行分析。结果 T1DM组GG基因型频率高于对照组频率(48.1%对31.9%,OR值2.615,95%CI 1.061~6.447,P0.05),且T1DM组G等位基因频率也高于对照组频率(69.8%对58.6%,OR值1.63,95%CI1.11~2.41,P0.05)。结论 CTLA4+49A/G基因多态性与天津地区TIDM相关,GG基因型与G等位基因显著增加TIDM的发病风险。     

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。     

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。     

新疆哈萨克族转化生长因子β1基因多态性及其血浆水平与原发性高血压的关系

目的 研究新疆哈萨克族原发性高血压(essential hypertension,EH)患者转化生长因子β1(transforming growth factor-β1,TGF-β1)+869T/C、+915G/C基因多态性及血浆水平与EH的关系.方法 采用聚合酶链反应-限制性片段长度多态性和基因测序对新疆哈萨克族365名EH患者及435名正常对照组进行基因分型,用双抗体夹心法测量TGF-β1血浆浓度.结果 +915G/C位点基因型GG、GC及等位基因G、C频率依次为97.9%、2.1%、98.77%、1.23%,EH组与对照组差异无统计学意义(P＞0.05);+869T/C位点基因型TT、TC、CC及等位基因T、C在对照组中频率依次为25.97%、46.67%、27.36%、49.3%、50.7%,CC基因型及C等位基因频率在EH组中高于对照组(41.60%vs.27.36%、62.2%vs.50.7%),差异有统计学意义(P＜0.05),C等位基因携带者EH患病风险高于T等位基因携带者(OR=1.6O,P=0.00).+869T/C与+915G/C存在连锁不平衡,其形成的单倍型C-G在EH组中频率高于对照组(61.6%vs.49.8%,P＜0.05).+869T/C及+915G/C基因型、等位基因在EH组和对照组中TGF-β1血浆水平差异无统计学意义(P＞0.05).结论 新疆哈萨克族TGFβ1+915G/C基因变异频率很低,且不存在纯合变异,+869位点C等位基因可能是哈萨克族EH的遗传易感基因,+869T/C与+915G/C多态性位点存在连锁不平衡,两者构成的单倍型C-G是EH危险性因素.     

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.