利用短串联重复序列产前基因诊断唐氏综合征

目的探索用STR-PCR方法进行唐氏综合征产前基因诊断的可行性。方法收集经羊水细胞培养、核型分析已确诊为唐氏综合征的孕妇羊水标本,提取其中的胎儿DNA,并利用聚合酶链反应扩增21号染色体上4个STR位点（D21S11、D21S1411、D21S2039、D21S2055）,根据扩增产物聚丙烯酰胺凝胶电泳分型结果诊断唐氏综合征患者。结果与核型分析结果对比。结果运用STR-PCR电泳分型技术对10例唐氏综合征孕妇的羊水进行诊断,结果与染色体核型分析一致。结论联用4个位点对唐氏综合征标准型患者进行诊断结果准确度高,适宜产前诊断临床应用。     

21三体综合征的快速基因诊断

目的探讨一种快速、简便、准确检测21三体综合征的基因诊断方法。方法选用位于21号染色体Down′s综合征核心区（21q21-21q22）内及其附近的短串联重复序列（STR）（D21S1432,D21S11,D21S1436,D21S1442,D21S1270,D21S1411,D21S1446）,建立STR-PCR快速诊断平台。通过对经染色体核型分析的10例正常胎儿的羊水脱落细胞DNA,及4例判定为21三体综合征胎儿的绒毛组织DNA进行21号染色体STR分析,从而进行方法评价。结果在上述7个STR位点中,10名正常胎儿除在D21S1436位点存在2∶1条带的占5/10,其余位点杂合度（64.29%-92.86%）及相互间的符合率为100%。4例21三体胎儿经6个STR位点联合分析,均被确诊为21三体综合征。结论6个STR位点（D21S1432,D21S11,D21S1442,D21S1270,D21S1411,D21S1446）可作为21三体综合征有价值的遗传标记,可用于对其做出快速、准确的基因诊断。     

用短串联重复序列诊断唐氏综合征

目的　建立一种准确、快速、简便的唐氏综合征 (Down's syndrome,DS)基因诊断技术。方法选择 10个位于 2 1号染色体上唐氏综合征关键区域内 (2 1q2 2 .1～ 2 1q2 2 .2 )或附近的短串联重复序列 (shrottandem repeats,STR)位点 ,应用 PCR与聚丙烯酰胺凝胶电泳或荧光 PCR(ABI 310 )进行 STR分型 ,根据STR位点出现 3条带图谱诊断 DS,荧光半定量的 2∶ 1带型可辅助诊断 ,并用细胞遗传学染色体核型分析进行证实。结果　在 2 0例可疑患者外周血中有 5例 DS阳性结果 ,其中 1～ 6个 STR位点呈 3条带图谱 ,其余为强度 2∶ 1的两条带型。 2 6例 DS的高危孕妇羊水细胞均未检出 3条带图谱和 2∶ 1图谱。基因诊断结果与细胞染色体核型分析一致。结论　联合进行 2 1号染色体上 10个 STR位点的基因分型 ,可准确、快速、简便地作出 DS的基因诊断 ,促进 DS产前诊断的开展 ,降低发病率。     

应用D21S11、D21S1440和Penta D短串联重复序列诊断唐氏综合征

目的 探讨应用短串联重复序列(short tandem repeat,STR)诊断唐氏综合征(Down's syndrome,DS)的可行性,为建立一种快速、准确诊断DS的技术提供依据.方法 用定量荧光聚合酶链反应扩增719份样本(包括外周血389例、羊水282例和绒毛48例)21号染色体上D21S11、D21S1440和Penta D STR基因座,通过对扩增产物条带的分析达到诊断DS的目的.结果 核型正常的652份样本中,635份表现为荧光强度为1∶1的2条带或1条带,17例表现3条带,为假阳性.67份DS样本均得到了诊断,53份样本出现1∶1∶1的3条带(峰),14份样本出现2:1的2条带(峰).D21S11、D21S1440和PentaD STR基因座诊断DS的灵敏度和特异度分别为76.12％和98.62％、71.64％和98.93％、89.55％和99.85％.联合应用3个基因座诊断DS的灵敏度为100％(67/67),特异度为97.39％(635/652).结论 用定量荧光聚合酶链反应扩增STR基因座具有灵敏度高、特异度强、简便、快速等优点,在临床上有广阔的应用前景,是大规模产前筛查DS的理想工具.     

昆明汉族人群D21S1411、IFNAR位点多态性及其在Down综合征基因诊断中的应用价值

目的 调查昆明汉族人群第21号染色体上D21S1411和IFNAR两个短串联重复序列（short tandem repeat,STR）的遗传多态性,探讨该2个STR基因座在唐氏综合征基因诊断中的应用价值。 方法 随机抽取100名昆明地区无血缘关系汉族正常个体及2名唐氏综合征患者的静脉血,应用PCR技术扩增D21S1411和IFNAR位点的STR片段,采用聚丙烯酰胺凝胶电泳,硝酸银染色分型,结合图像分析系统测定等位基因片段大小。 结果 昆明汉族人群D21S1411和IFNAR等位片段分别为6、7;2个位点的基因型分布均符合Hardy-Weinberg平衡;各位点杂合度分别为0.87、0.82,多态信息含量分别为0.8062、0.8365。2例Down综合征患者,在IFNAR位点上,均出现DNA含量为2：1的2条带;在D21S1411位点上,1名出现DNA含量为1：1：1的3条带,1名出现2：1的2条带。 结论 D21S1411、IFNAR是两个多态信息含量比较高的基因座,在法医学及唐氏综合征基因诊断中具有较高的应用价值。     

昆明汉族人群D21S1411、IFNAR位点多态性及其在唐氏综合征基因诊断中的应用

目的 调查昆明汉族人群第21号染色体上D21S1411和IFNAR两个短串联重复序列（short tandem repeat，STR）的遗传多态性，探讨该2个STR基因座在唐氏综合征基因诊断中的应用价值。 方法 随机抽取100名昆明地区无血缘关系汉族正常个体及2名唐氏综合征患者的静脉血，应用PCR技术扩增D21S1411和IFNAR位点的STR片段，采用聚丙烯酰胺凝胶电泳，硝酸银染色分型，结合图像分析系统测定等位基因片段大小。 结果 昆明汉族人群D21S1411和IFNAR等位片段分别为6、7；2个位点的基因型分布均符合Hardy-Weinberg平衡；各位点杂合度分别为0.87、0.82，多态信息含量分别为0.8062、0.8365。2例Down综合征患者，在IFNAR位点上，均出现DNA含量为2：1的2条带；在D21S1411位点上，1名出现DNA含量为1：1：1的3条带，1名出现2：1的2条带。 结论 D21S1411、IFNAR是两个多态信息含量比较高的基因座，在法医学及唐氏综合征基因诊断中具有较高的应用价值。     

天津地区D21S1411和D21S1413 2个STR基因座遗传多态性的研究

目的研究天津地区D21S1411和D21S14132个STR基因座的遗传多态性,探讨其在唐氏综合征基因诊断及产前基因诊断应用的可行性。方法随机选择301例天津地区无亲缘关系的汉族个体及313例染色体核型分析正常的胎儿样本,盐析法提取DNA,聚合酶链式反应扩增,非变形聚丙烯酰胺凝胶电泳,硝酸银染色,凝胶图像分析管理系统分析扩增产物。结果D21S1411基因座共发现9种等位基因、45种基因型;D21S1413基因座共发现7种等位基因、28种基因型。外周血样本D21S1411基因座的PIC、DP、PE和Ho分别为0．85、0．967、0．483和73．4％,D21S1413基因座的PIC、DP、PE和Ho分别为n83、0．949、0.719和86．20k;胎儿样本D21S1411基因座的PIC、DP、PE和H0分别为0．80、n927、0．494和78．5％,D21S1413基因座的PIC、DP、PE和Ho分别为0．76、0．915、0．808和87．2％。结论D21S1411和D21S14132个STR基因座基因杂合度高、具有高鉴别力,是21号染色体上理想的遗传标记,可用于DS的基因诊断及产前基因诊断。     

北京汉族群体21号染色体上4个STR位点的遗传多态性

目的研究人类21号染色体上唐氏综合症关键区域内或附近的4个短串联重复序列(D21S1432、D21S2039、D21S1414、D21S1270)在中国汉族人群中的遗传多态性。方法应用Chelex法提取北京地区无血缘关系汉族253份个体血样DNA,聚合酶链式反应(PCR)扩增,非变性聚丙酰胺凝胶电泳或ABI鄄310电泳分型结合测序进行STR分型。结果得到4个STR基因座等位基因频率、各基因座的杂合度、个体识别率、多态信息含量等群体遗传学数据。4个位点基因型分布均符合Hardy鄄Weinberg平衡定律。结论21号染色体上4个STR位点多态性较好,基因型分布符合Hardy鄄Weinberg平衡定律,具有较高的个体识别率,在法医学及唐氏综合征的基因诊断和产前基因诊断研究中具有较高的应用价值。     

应用STR-荧光定量PCR行产前唐氏综合征诊断的初步研究

目的建立快速高效的产前诊断唐氏综合征的方法。方法选取21号染色体上唐氏综合征关键区域内的4个串联重复序列（STR）（D21S1413,D21S1414,D21S1446,D21S1437）作为遗传标记,采用荧光定量PCR扩增技术（QF—PCR）及片段分析技术来检测178例羊水标本,并与羊水标本的染色体核型分析结果相比对,评价QF—PCR方法的特异性和灵敏度。结果所有178例羊水标本中经核型分析证实有19例为21三体,另有2例为性染色体数目异常,19例唐氏综合征样本均可由QF—PCR法扩增检出。19例唐氏综合症样本,采用4对STR引物同时检测,阳性诊断率达100％。结论基于STR的QF—PCR技术具有简单、快速及准确等优点,对唐氏综合征大规模的产前基因诊断具有很好的临床价值。     

STR基因在胎儿21三体异常中的表达

目的探讨应用短串联重复序列（STR）基因对胎儿细胞进行21三体定性诊断的可行性。方法选择31例高风险胎儿及其双亲为对象，抽提羊水细胞基因组DNA，用聚合酶链反应扩增D21S1 411、D21S1414、D21S1412和D21S11位点的STR片段，并对其进行单链构象多态性分析，通过DNA密度扫描定量分析特征诊断21三体。以脐带血染色体G显带核型分析为对照。结果本法可以通过检测STR片段DNA密度扫描定量分析来诊断21三体。应用谊基因诊断方法鉴别出21三体的胎儿9例，其诊断结果与细胞遗传学核型分析结果相符。结论STR基因的聚合酶链反应一单链构象多态性分析技术是一种简单、快速和可靠的21三体定性基因诊断技术，可应用于21三体的微创基因诊断和遗传筛查。     

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.     

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 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.