可育男性减数分裂遗传重组分析

目的 探讨可育男性减数分裂前期Ⅰ同源染色体的联会和重组.方法 应用铺展技术制备精母细胞联会复合体,以SCP3抗体、MLH1抗体和CREST抗血清孵育来显示联会复合体侧轴、重组位点和着丝点.结果 5例可育男性中,粗线期细胞的比例介于67%～78%;每个细胞中重组位点数平均为46.1±3.9,范围为34～61,具有显著的个体差异;联会复合体上出现缺口(gap)或未配对区(split)的细胞比例分别为14.3%和2.9%.结论 可育男性的遗传重组频率具有显著的个体差异.     

联会复合体的硝酸银染色技术

联会复合体是减数分裂前期Ⅰ出现的一种核内非永久性细胞器,与同源染色体联会、交换、重组、分离有着密切的关系,早期研究联会复合体是通过减数分裂前期细胞连续超薄切片进行三维重组。这种方法费时费力,观察细胞数目有限,不仅不能用光镜观察,而且在一张超薄切片上不可能观察到一条完整的联会复合体,更谈不上一整套联会复合体。Counce和Meyer首次用微铺展技术,成功地把蝗虫初级精母细胞的一整套联会复合体铺展在载玻片上,运用磷钨酸染色方法在电镜下看到了联会复合体的三层结构[1]。1977年,     

广东惠州地区653例非梗阻性无精子症患者的细胞遗传学分析

目的探讨非梗阻性无精子症(NOA)与染色体异常及多态之间的关系。方法选取临床诊断为NOA的653例男性患者行常规外周血染色体G显带核型分析和Y染色体AZF微缺失检测,同时选取487例正常生育男性作为对照组。结果 653例NOA患者中,性染色体异常发生率为18.68%(122/653),常染色体异常率为2.76%(18/653),染色体多态占5.97%(39/653)。精液正常对照组中,性染色体异常率为0.62%(3/487),常染色体异常率为0.82%(4/487),染色体多态占6.98%(34/487)。NOA组与精液正常对照组进行比较:性染色体异常,有显著性差异(χ2=93.27,P0.05);常染色体异常,有显著性差异(χ2=5.52,P0.05);染色体多态性,无显著性差异(χ2=0.09,P0.05)。NOA组患者共检出Y染色体微缺失34例,其中AZFa微缺失2例,AZFb微缺失5例,AZFc微缺失18例,AZFb+AZFc微缺失5例,AZFa+AZFc微缺失1例,AZFa+AZFb+AZFc微缺失3例。结论性染色体数目异常和Y染色体结构的异常是导致NOA的一个重要因素,对NOA患者行染色体检查是十分必要的;染色体多态与NOA无明显相关性。     

无精症及隐匿精子症患者染色体核型与Y染色体微缺失分析

目的 研究无精症和隐匿精子症染色体核型与Y染色体无精因子(azoospermia factor,AZF)微缺失的发生频率及其关系.方法 对997例无精症和隐匿精子症患者进行常规染色体核型分析及多重聚合酶链反应技术检测AZF位点.结果 在997例无精症和隐匿精子症患者中,染色体核型异常检出率28.4%,异常核型包括47,XXY、46,XY(Y＜G)、46,XX、嵌合体及相互易位等.AZF微缺失总检出率17.4%.常见于46,XY及46,XY(Y＜G)等核型.结论 染色体核型异常是无精症和隐匿精子症的重要遗传病因.正常核型与Y＜G患者中存在较高的AZF微缺失率,对这些患者进行AZF微缺失检查有助于明确病因,避免一些不必要的临床治疗及遗传缺陷的垂直传递.     

几种实验啮齿动物精母细胞联会复合体的初步观察

本文对实验啮齿动物豚鼠、兔、大白鼠、小白鼠(津白Ⅰ号、津白Ⅱ号和昆明种)精母细胞联会复合体进行了观察。其联会复合体基本组成是相同的,如都包括2条侧体和两侧体间的空间中的一条中体,并有较细的横丝等,但在形态上,还存在一定差异。同源染色体和其间的联会复合体,吸附于核内膜上,核内膜加厚形成板状物,其中体明显到达核膜。性泡是X染色体和Y染色体在减数分裂期间配对。小鼠核仁密切联系性泡。性泡也可紧密贴于核膜,中体上存在有数目不等的小结节。     

经皮附睾或睾丸抽吸取精结合ICSI治疗无精子症

目的评价经皮附睾精子抽吸术（percutaneus epididymal sperm aspiration,PESA）或睾丸精子抽吸术（testicu1ar sperm aspiration,TESA）结合卵胞浆内单精子注射（intracytoplasmic sperm injection,ICSI）治疗无精子症的临床效果。方法对290例因男性梗阻性及非梗阻性无精子症（non-obstructive azoospermia,NOA）采用PESA或TESA穿刺获取精子,女方采用长方案超排卵,然后对处于细胞分裂中期的成熟卵母细胞进行单精予注射。结果梗阻性无精子症组203例,受精率77．5％,临床妊娠率46．1％;非梗阻性无精子症组87例,受精率73．O％,临床妊娠率41．4％,两组比较其受精率及临床妊娠率均无显著性差异（P〉0．05）。结论采用PESA或TESA获取精子结合ICSI是治疗梗阻性及非梗阻性无精子症等严重的男性不育症的一种有效的方法。     

采用抽吸取精法结合单精子注射治疗无精子症结局

目的评价经皮附睾精子抽吸术（percutaneus epididymal sperm aspiration,PESA）或睾丸精子抽吸术（testicular sperm aspiration,TESA）结合卵胞浆内单精子注射（intracytoplasmic sperm injection,ICSI）治疗无精子症的临床效果。方法对290例因男性梗阻性及非梗阻性无精子症（non-obstructive azoospermia,NOA）采用PESA或TESA穿刺获取精子,女方采用长方案超排卵,然后对处于细胞分裂中期的成熟卵母细胞进行单精子注射。结果梗阻性无精子症组203例,受精率77.5%,临床妊娠率46.1%;非梗阻性无精子症组87例,受精率73.0%,临床妊娠率41.4%,两组比较其受精率及临床妊娠率均无显著性差异（P〉0.05）。结论采用PESA或TESA获取精子结合ICSI是治疗梗阻性及非梗阻性无精子症等严重的男性不育症的一种有效的方法。     

男性不育患者Y染色体AZF基因微缺失检测

目的探讨原发性无精子症、严重少精子症及少精子症患者与Y染色体无精子因子（azoospermia factor,AZF）区微缺失的关系。方法采用多重PCR方法对对照组192例已正常生育男性和实验组448例男性不育患者进行AZF区域内的15个序列标签位点（STS）的检测。结果对照组未发现AZF基因微缺失,实验组448例患者检测出五种AZF微缺失类型共41例,总缺失率为9.2%（41/448）,其中无精子症、严重少精子症和少精子症患者的缺失率分别为12.0%（19/158）、10.8%（17/157）、3.8%（5/133）,无精子症和严重少精子症患者Y染色体AZF微缺失率明显高于少精子症组,差别有统计学意义（P〈0.05）。使用15个STS位点进行检测其检出率较利用欧洲男科学会（European Academy of Andrology,EAA）推荐的6个STS位点提高约14%（5/36）。结论AZF微缺失是引起原发性无精子症、严重少精子症和少精子症的重要原因之一;增加STS位点检测数有利于提高AZF微缺失的检出率。     

男性不育患者Y染色体微缺失的研究

目的研究无精子症和少精子症患者与Y染色体位点缺失的相关性，建立Y染色体微缺失的分子诊断方法。方法采用多重PCR技术对53例染色体核型正常的无精子症和少精子症患者以及5例正常男性的无精子因子（azoospermia factor，AZF）区域的6个STS位点进行检测。结果5例精液正常男性未检出Y染色体微缺失；53例患者中6例有AZF区域的微缺失，总缺失率为11．3％。结论Y染色体微缺失是严重生精障碍的重要原因之一，无精子因子（AZF）候选基因在精子发生过程中可能起重要作用。     

梗阻性和非梗阻性无精子症患者睾丸组织来源iPSCs系的建立

目的利用梗阻性无精子症(OA)和非梗阻性无精子症(NOA)患者的睾丸组织建立诱导性多能干细胞(iPSCs)系,比较两者建系过程有无差别。方法分别取3例OA患者和特发性NOA患者5～6 mm~3的睾丸组织,组织块培养方法进行原代培养,传至3～4代转染仙台病毒,待细胞增殖满后转移至饲养层细胞上继续培养,第21～22天挑取克隆,建立iPSCs系并进行多能性和分化能力的鉴定。结果两株iPSCs系均成功建立,建系过程无明显差异,碱性磷酸酶(AP)染色均为阳性;八聚体结合转录因子4(OCT4)、性别决定基因相关蛋白2(SOX2)、阶段特异性胚胎抗原-4(SSEA-4)、肿瘤排斥抗原-1-60(TRA-1-60)的免疫荧光染色均为阳性;小鼠体内的畸胎瘤实验也表明获得的两株iPSCs系具有向3个胚层分化的潜能。结论利用仙台病毒非基因整合方法,OA患者和特发性NOA患者的睾丸组织均能建立iPSCs系。     

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.