不育男性的AZF检测与Y染色体缺失的对照分析

目的探讨精子发生障碍的男性不育患者AZF缺失与Y染色体缺失的临床意义。方法对616例非阻塞性无精子症或少精子症患者进行AZF的检测,同时观察G显带Y染色体的形态。结果从616例患者中检测出48例患者分别为AZFa、AZFb、AZFc或AZFb+AZFc的微缺失,但显微镜下观察不到Y染色体形态改变。另外4例患者经AZF检测,2例为AZFc+sY160缺失,1例为AZFb+AZFc+sY160缺失,1例为AZFa+AZFb+AZFc+sY160缺失,显微镜下发现Yq部分或完全缺失。25例已育男性的G-显带的Y染色体和AZF也进行对照检测,均未发现AZF的缺失,但其中1例核型分析显示Y染色体长臂部分缺失,但PCR检测仅缺失sY160,即Yq12的缺失。结论Yq11.23上7Mb的缺失在细胞水平不能分辨。q11.23+q12的缺失或仅有Yq12的缺失的Y染色体显微镜下不能区分,但后者不是精子发生障碍的病因。对男性不育精子发生障碍患者,要结合细胞遗传学和AZF分子检测综合判断。     

甘肃部分地区373例男性不育患者Y染色体AZF微缺失基因诊断的研究

目的研究甘肃地区男性不育患者Y染色体AZF区域微缺失的频率、分布情况方法采用多重PCR技术,对甘肃地区373例男性不育症患者进行Y染色体AZFa,AZFb,AZFc三个区域6个STS位点的微缺失检测。结果 373例男性不育患者中,42例发生了STS位点缺失,缺失率11.3%。其中无精子症因子AZFa(SY86,SY84)区未见缺失;AZFb(SY127,SY134)区缺失4例(9.52%);AZFc(SY254,SY255)区缺失32例(76.2%);AZFb+c区缺失5例(11.9%);AZFa+b+c缺失1例(2.38%)。结论甘肃部分地区AZF区域微缺失的频率、分布与国内其他报道一致,但是在本研究中未检测到AZFa区缺失患者。     

特发性无精子症及少弱精子症患者Y染色体AZF微缺失筛查分析

目的探讨特发性无精子症及少弱精子症不育男性与Y染色体AZF微缺失的关系.方法用双重PCR技术对63例患者(无精于症41例,少弱精子症14例,严重少精子症8例)进行Y染色体AZFa、AZFb、AZFc、SRY的微缺失筛查.同时对26例无精于症患者行睾丸活检、组织学评估.结果63例中AZF微缺失7例,缺失率为11.1%.其中无精子症5例,严重少精子症2例.AZFc缺失4例,AZFb缺失2例,AZFb AZFc缺失1例,未发现AZFa区缺失.63例及对照组30例SRY基因扩增均阳性.26例无精子症患者行睾丸活检、组织学检查,无1例精子发生正常.结论Y染色体微缺失,特别是AZFc区DAZ基因的微缺失,是引起无精子和严重少弱精子等生精障碍而致男性不育较为重要的遗传学因素.     

一例Y染色体长臂大片段缺失患者的缺失定位分析

目的 从分子遗传学角度对1例无精子症患者Y染色体无精子因子(azoospermia factor,AZF)区域缺失片段进行定位分析.方法 根据Y染色体遗传物理图谱,采用多重PCR技术扩增Y染色体AZFa区sY84、sY86、sY87,AZFb区sY102、sY117、sY118、sY119、sY115、DYS132、DYS385、sY1015、sY121、sY125、sY127、sY129、sY134,AZFd区sY152,AZFc区sY1258、sY1291、sY254、sY255、sY158、sY1201,Yq末端sY160等24个序列标签位点(sequence tag sites,SIS).结果 所扩增的SIS只有AZFa区sY84、sY86、sY87及AZFb区sY102、sY117、sY118、sY119、sY115、DYS132有特异扩增条带,其余15个STS均未见特异扩增条带.患者Y染色体缺失断裂点位于AZFb区sY115和DYS385之间约8577 bp范围内.为AZFb区部份缺失,AZFd区、AZFc区及Yq末端缺失.结论 用分子遗传学技术进行STS分析可精确标明Y染色体AZF区域缺失片段.     

618例不育男性的AZF基因微缺失分析

目的研究Y染色体AZF基因微缺失与男性不育的关系。方法应用多重PCR对618例男性不育患者进行Y染色体AZF基因的15个位点进行检测。结果一共检出Y染色体微缺失患者23例,占受检人群的3．72％,其中包括16例AZFc全部缺失、3例为AZFb＋c部分／全部缺失、3例为AZFa部分缺失和1例AZFa、AZFb、AZFc和AZFd四个区15个检测位点全部缺失。AZFc全部缺失患者中,中度至重度少精症13例,无精症3例;AZFb部分／全部缺失患者中,严重少弱精1例,无精症2例;AZFa部分缺失患者和15个位点全部缺失患者均为无精症。结论Y染色体AZF基因微缺失是男性不育的重要原因之一,该检测可为患者的诊断、治疗及遗传咨询提供依据。     

1011例男性不育患者Y染色体无精子症因子微缺失的筛查与临床表型分析

目的 探讨四川地区近6年不育男性Y染色体无精子症因子(azoospermia factor,AZF)微缺失的发生率、缺失类型及其与临床表型的关系.方法 应用多重PCR方法对713例非梗阻性无精症和298例重度少精症的男性进行Y染色体AZF微缺失分析.结果 AZF总体缺失率为10.48％ (106/1011),其中非梗阻性无精症患者缺失率为11.08％ (79/713),重度少精症患者缺失率为9.06％ (27/298).AZFa与AZFb完全缺失者均表现为无精症.AZFc缺失为最常见缺失类型且具有多种表型,占60.38％,其中37.50％的缺失者精液中有成熟精子.2例AZFb和1例AZFb-c部分缺失者精子密度呈轻度下降.结论 AZFc区是Y染色体AZF微缺失的缺失热点,AZFa或AZFb缺失者以及部分AZFc缺失者均表现为无精症.本研究进一步明确了AZF缺失基因型与表型的关系,证实Y染色体AZF微缺失检测对诊断男性不育具有重要的价值.     

广西毛南族17个Y染色体短串联重复序列基因座遗传多态性

目的:调查17个Y染色体短串联重复序列(Y-STR)基因座及其单倍型在广西毛南族人群中的分布情况.方法:应用AmpFlSTR YfilerTM荧光标记复合扩增系统,对毛南族208名无关男性个体血样进行17个Y-STR位点的复合扩增,用ABI PRISM310遗传分析仪对扩增产物进行检测分析.结果:DYS456、 DYS389Ⅰ、 DYS390、 DYS389Ⅱ、 DYS458、 DYS19、 DYS385a＼b、 DYS393、 DYS391、 DYS439、 DYS635、 DYS392、 Y-GATA-H4、 DYS437、 DYS438、 DYS448各位点遗传多样性(GD值)分布在0 5852～0 9770之间.17个Y-STR位点共同构成的单倍型205种,其单倍型多样性为0 999785.广西毛南族与其他群体的Y-STR位点等位基因分布差异具有统计学意义.结论:广西毛南族17个Y-STR位点具有丰富的遗传多样性,可为父权鉴定和父系进化研究提供有价值的遗传学资料.     

新疆地区汉、维吾尔族男性无精子患者与Y染色体微缺失关系的研究

目的探讨检测男性不育症患者Y染色体微缺失的临床意义。方法引用多重聚合酶链反应(PCR)对门诊392例男性不育患者行Y染色体AZFa、AZFb、AZFc、AZFd和SRY20个序列标签位点(STS)设计特异引物进行微缺失检测,同时进行精液常规检查。结果 392例男性不育患者中AZF基因微缺失患者共检出24例,总缺失率为6.12%,其中汉族无精子症组缺失率为6.19%,维吾尔族(以下简称维族)无精子症组缺失率为18.92%,汉、维族不育症患者Y染色体AZF微缺失率比较差异无统计学意义(P0.05);汉、维族无精子症患者Y染色体AZF微缺失率比较差异有统计学意义(χ2=5.333,P=0.021),汉族与维族的Y染色体多位点联合缺失发生率比较差异有统计学意义(χ2=4.168,P=0.041)。结论汉、维族不育症男性患者中Y染色体AZF微缺失发生率存在种族差异,PCR检测AZF基因是诊断Y染色体AZF微缺失的较好的方法。     

广西黑衣壮族17个Y-STR位点遗传多态性

目的　调查17个Y染色体短串联重复序列(Y-STR) 基因座及其单倍型在广西黑衣壮族人群中的分布情况。方法　应用AmpFlSTR? Yfiler?荧光标记复合扩增系统,对黑衣壮族184名无关男性个体血样进行17个Y-STR位点的复合扩增,用ABI PRISM 310遗传分析仪对扩增产物进行检测分析。结果　DYS456、DYS389Ⅰ、DYS390、DYS389Ⅱ、DYS458、DYS19、DYS385a\b、DYS393、DYS391、DYS439、DYS635、DYS392、Y-GATA-H4、DYS437、DYS438、DYS448各位点遗传多样性(GD 值) 分布在0. 4910～0.9727之间。17个Y-STR 位点共同构成的单倍型180种,其单倍型多样性为0.99976。广西黑衣壮族与其他群体的Y-STR位点等位基因分布差异具有统计学意义。结论　广西黑衣壮族17个Y-STR位点具有丰富的遗传多样性,可为父权鉴定和父系进化研究提供有价值的遗传学资料。     

Y染色体AZF区遗传学研究进展

Y染色体无精子症因子（azoospermia factor,AZF）区域微缺失与男性不育密切相关,是最常见的导致无精子症与严重少精子症的分子遗传病因。AZF区域包括三个遗传域AZFa区,AZFb区和AZFc区。在本文中将对AZF基因结构和功能作一综述。     

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.