脆性X综合征外周血淋巴细胞永生化细胞系的建立与验证

正脆性X综合征(fragile X syndrome,FXS)是一种X连锁不完全外显性遗传病,是引起遗传性智力低下和孤独症谱系障碍最常见的单基因病[1],因细胞中X染色体末端在特殊培养基中经诱变剂作用后可显示如同断裂的脆性部位而得名。男性患者多见且症状较重,表现为智力低下、巨睾、     

脆性X综合征的细胞遗传学研究

本研究从１０个Ｘ－连锁智力低下家系中，经细胞遗传学检查，检测出５个Ｆｒａ（Ｘ）综合征家系，共１５名患者和携带者检查发现：１、不同成份培养液对脆性Ｘ表达有影响。２、活性Ｘ染色体Ｘｑ２７迟复制与Ｆｒａ（Ｘ）综合征患者智力密切相关。３、Ｆｒａ（Ｘ）染色体的活性与女性携带者的智力有一定的关系     

Fra(X)与FMR-1基因表达的研究现状

196 9年Ｌｕｂｓ首先报告了Ｘ连锁智力低下与Ｘ染色体的脆性位点有关。人类ｆｒａ(Ｘｑ2 7.3)指Ｘ染色体长臂末端 2区 7带的断裂或随体样改变。具有这类变化的Ｘ染色体称为脆性Ｘ染色体 ,又称标记Ｘ染色体。脆性Ｘ在严重智力低下男性中占 7% ;在轻微智力低下男性中占 4.5 % [1] 。脆性Ｘ综合征是通过ｆｒａ(Ｘｑ2 7.3)遗传的Ｘ连锁智力低下综合征。近来Ｍｕｌｌｉｇａｎ己将与该综合征有关的脆性位点 ,准确地定位在Ｘｑ2 7.3[2 ] 。Ｈｅｒｂｓｔ报告脆性Ｘ综合征在出生男性中发病率约为 0 .92‰[3 ] 。可见脆性Ｘ综合征是男性智力低下的较常…     

35例智力低下儿童染色体脆性部位分析

３５例智力低下儿童染色体脆性部位分析张晓珍，余继英，霍晓春，饶兆英近年来，对脆性Ｘ综合征的研究引起了医学遗传学界的广泛关注。脆性Ｘ染色体（ＦｒａＸ）与Ｘ连锁智力低下（ｍｅｎｔａｌｒｅｔａｒｄａｔｉｏｎ，ＭＲ）有关，进而使人们对罕见型脆性位点发生极大兴...     

脆性X染色体综合征的临床特征及细胞遗传学研究

一、脆性X染色体综合征的临床特征根据外表特征鉴别有脆性X染色体的人是十分困难的,即使在智力低下的人群中,也很难决定那一个病例值得进一步研究。目前,筛选的方法:一是研究X-连锁智力低下家系中的成员;二是根据某些临床特征作进一步研究,如像Down综合征那样。脆性X综合征有些临床特征对诊断具有一定价值。与脆性X染色体相关的主要临床特征包括智力低下、巨睾症、特殊面容、语言障碍及行为异常等方面,现分别介绍如下: 智力低下:脆性X综合征智力缺陷的程度变化范围较大。通常,半合子表现较严重     

脆性X综合征：FMR－1基因的分离及脆性X突变的特征

脆性Ｘ综合征是家族性智力低下的最常见原因。脆性Ｘ染色体的分子生物学研究已经取得了重大突破，使用ＹＡＣ克隆的方法已经克隆出ＦＭＲ—１基因。ＦＭＲ－１基因外显子区ＣＧＧ重复的扩增及甲基化是脆性Ｘ综合征产生的原因。本文对ＤＮＡ分析法用于脆性Ｘ综合征产前诊断和携带者检出也进行了讨论。     

脆性X综合征的临床和遗传方式探讨

脆性Ｘ综合征是非特异性Ｘ连锁智力低下综合征。本文通过二个家系２４ 人的调查分析,将智力低下、语言障碍、多动,视作脆性Ｘ 综合征最明显的临床特征。本病遗传有其特殊的遗传方式：（１）脆Ｘ 综合征是由表型正常的男性传递。（２） 表型正常的男性携带者通常是男性患者的外祖父。（３） 脆Ｘ综合征家系中,智力低下男性患者比予期的约少２０ ％ ,低于Ｘ连锁基因所予期的数值。（４）本综合征患儿母亲几乎均是携带者。（５） 表型异常的女性ｆｒａ（ｘ）来自母亲而非来自父亲。（６）同胞中外显程度不一致。对患者及携带者的确切诊断是依靠染色体显示Ｘｑ２７ ．３ 位置的脆位点。     

脆性X综合征：FMR—1基因的分离及脆性X突变的特征

脆性Ｘ综合征是家族性智力低下的最常见原因。脆性Ｘ染色体的分子生物学研究已经取得了重大突破。使用ＹＡＣ克隆的方法已经克隆出ＦＭＲ－１基因外显子区ＣＧＧ重复的扩增及甲基化是脆性Ｘ综合征产生的原因。本文对ＤＮＡ分析法用脆性Ｘ性综合征产前诊断和携带者检出也进行了讨论。     

核苷酸在人类脆性位点表达中的作用

具有脆性X染色体的智力低下综合征,是男性智力低下最常见的遗传方式。脆性X染色体的特征是在X染色体长臂末端附近具有一脆性位点。脆性位点是指细胞于细胞周期的S期暴露于特定的培养基时,在染色体上出现的断裂或者裂隙。X染色体上脆性位点与相伴随的症状之间关系的本质还不清楚。此病遗传方式非同一般,已发现有男性携带者,且母亲的表型可影响子女的表型,这两种现象都无法用经典遗传学理论来解释。     

脆性X染色体综合征

脆性X染色体综合征是一种性连锁遗传性疾病,其患病率大约为0.73～0.92‰,仅次于先天愚型。临床特征为,智力障碍多为中度到重度,语言发育缓慢,行为孤独。颜面狭长、大耳壳、大睾丸及大生殖器为其明显的特殊体征。本综合征的诊断主要以染色体分析结果为依据,只有X染色体的一部分显示有“脆性部位”才能确定诊断。从优生的角度来讲,特别重要的是防止出生脆性X综合征的患儿,对携带者怀孕时进行产前诊断,并对确诊为本综合征的男胎终止妊娠,以防止智力低下患儿的出生。根据多数作者的报道,叶酸可以改善患者(尤其是青春期前患者)的行为甚至智力,其治疗作用与患者的病情轻重,叶酸的剂量及疗程的长短等因素有关。     

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.