多巴胺D4受体和COMT基因多态性在精神分裂症患者攻击行为中的交互作用

目的:讨论多巴胺D4受体(DRD4)基因第3外显子48bp可重复序列多态性(exon Ⅲ 48 bp VNTR)和COMT val158met基因多态性及其交互作用对精神分裂症患者攻击行为的影响.方法:采用修改版外显攻击行为量表(MOAS)对301例精神分裂症患者进行分组,分为伴攻击行为组(研究组)和不伴攻击行为组(对照组),分别进行社会人口学资料、阳性和阴性症状量表(PANSS)测定,采用多聚酶链反应-限制性片断长度多态性技术检测DRD4 exon Ⅲ 48 bp VNTR 和 COMT val158met 基因多态性.采用 logistic 逐步回归分析 DRD4 exon Ⅲ 48 bp VNTR和COMT val158met基因多态性及其交互作用的效应.结果:除既往攻击行为史(t=13.118,P＜0.01)外,两组间社会人口学资料差异无统计学意义(P＞0.05);两组DRD4 exon Ⅲ 48 bp VNTR和COMT va1158met基因的等位基因及基因型频率分布比较均有统计学意义(X2＝13.232,14.384,9.108,4.436;P＜0.05);COMT Val/Met和DRD42/2/2、2/4、3/4基因型多态性的交互作用可影响精神分裂症的攻击行为,其OR值(95％CI)为0.195(0.042～0.918).结论:①DRD4 exon Ⅲ 48 bp VNTR和COMT val158met基因多态性可能与精神分裂症患者攻击行为存在关联;②COMT Val/Met和DRD42/2/2、2/4、3/4基因型多态性对精神分裂症攻击行为存在负交互作用.     

住院精神分裂症患者攻击行为的特征及相关风险因素

目的:探索住院精神分裂症患者攻击行为的特征,探讨个人成长环境对攻击行为发生的影响。方法:选取416例符合疾病和有关健康问题的国际统计分类第十次修订本(ICD-10)中精神分裂症标准的住院患者,使用阳性和阴性症状量表(PANSS)、外显攻击行为量表(MOAS)和攻击行为危险因素自编问卷评估患者精神症状、攻击行为及其环境影响因素。结果:住院精神分裂症患者外显攻击行为发生率47.8%(199/416)。其中,男性体力攻击行为显著多于女性(35.5%vs.19.6%,P0.001)。患者存在两种以上攻击行为的比率为32.9%。非条件logistic回归分析结果显示:PANSS阳性症状高分(OR=1.12,P0.001)是攻击行为发生的危险性因素,女性(OR=0.61,P0.05)、与父亲关系融洽(OR=0.74,P0.05)和父亲无家暴(OR=0.39,P0.01)是攻击行为发生的保护性因素。结论:本研究提示近半数住院精神分裂症患者存在外显攻击行为,相对较好的个人成长环境可能在一定程度上会降低攻击行为的发生。     

精神分裂症患者攻击行为与执行功能的相关性

目的:探讨精神分裂症患者攻击行为与执行功能的关系。方法:采用修改版外显攻击行为量表(MOAS)对142例精神分裂症患者进行攻击行为评估,分为攻击组(n=62)和非攻击组(n=80)。采用威斯康星卡片分类测验(WCST)评估执行功能,阳性与阴性症状量表(PANSS)评估临床症状,比较两组WCST成绩并对MOAS分与相关因素进行分析。结果:两组患者在性别、婚姻、受教育程度、职业、年龄、病程方面差异均无统计学意义。攻击组PANSS总分、阳性症状分、阴性症状分和一般精神病理分高于非攻击组(t=5.193,3.926,2.419,2.983;P均0.01)。在WCST中,攻击组非持续错误数、持续错误数、完成第一个分类所需应答数高于非攻击组(t=3.445,5.809,2.703;P均0.01),完成分类数和正确应答数低于非攻击组(t=-2.449,-2.468;P均0.01)。MOAS分与PANSS总分、阳性症状分、阴性症状分和一般精神病理分呈显著正相关(r=0.391,0.472,0.257,0.418;P均0.01)。MOAS分与WCST完成分类数(Cc)、非持续错误数(nRpe)、持续错误数(Rpe)、正确应答数(Rc)、完成第一个分类所需应答数(Rf)5个变量指标评分的相关系数有统计学意义,呈显著正相关(r=0.382,0.315,0.438,0.240,0.423;P均0.01)。结论:精神分裂症攻击行为与执行功能损害有关,伴攻击行为的精神分裂症患者存在更差的执行功能。执行功能受损可能是发生攻击行为的病理基础之一。     

儿茶酚-O-甲基转移酶基因Val158Met多态性与催眠感受性的关联研究

目的 探讨儿茶酚-O-甲基转移酶基因(catechol-O-methytransferase,COMT)Val158Met多态性与催眠感受性有无关联.方法 成都市6所高校120名正常汉族大学生参加了实验.按斯坦福团体催眠感受性量表C式(Stanford Group Hypnotic Susceptibility Scale,Form C,SGHSS:C)进行划分,总分0～5分为低催眠感受性组,6～11分为高催眠感受性组.聚合酶链反应-限制性片段长度多态方法检测COMT基因Val158Met多态.结果 在男性样本中,VaL/Val纯合子可能与催眠高感受性关联(VaL/Val vs.Val/Met:0R=5.33,P=0.034;VaL/Val vs.VaL/Met+/Met/Met:OR=4.86,P=0.031).在总样本及女性组中无关联.3种基因型组别样本的催眠感受性差异没有统计学意义.结论 COMT基因val158Met多态可能与男性催眠高感受性父联.该发现有待于增加样本加以证实.     

精神分裂症断裂基因1(DISC1)多态性与精神分裂症的关联研究

目的:探讨精神分裂症断裂基因1(DISC1)与精神分裂症及临床症状的遗传关联.方法:应用病例对照关联研究设计,采用聚合酶链式反应-限制性片断长度多态性(PCR-RFLP)方法:分析466例精神分裂症患者和551例正常对照者DISC1基因2个单核苷酸多态性(SNP)位点与精神分裂症的关联.并采用阳性和阴性症状量表(PANSS)评估患者的临床症状,进一步分析PANSS因子分与DISC1多态性的关联.结果:DISC1基因的两个多态性位点rs821597(等位基因A>G,χ2=6.009,P=0.014;基因型:χ2=6.505,P=0.039)和rs821616(等位基因A>T,χ2=7.063,P=0.008;基因型:χ2=6.928,P=0.031)均与精神分裂症显著关联.由上述2个SNPs组成的多个单体型均与精神分裂症关联[如AT(χ2=7.065,P=0.008,OR=1.42,95%CI=1.10～1.83)和GA(χ2=6.009,P=0.014,OR=0.80,95%CI=0.68～0.96)].上述2个SNPs组成的风险单体型AT间PANSS量表各因子分差异均无统计学意义(均P>0.05).结论:DISC1基因多态性与精神分裂症显著关联,但与精神分裂症症状无关联.     

注意缺陷多动障碍与儿茶酚-O-甲基转移酶基因Val158Met多态性的关联分析

目的探讨注意缺陷多动障碍(attention-deficit hyperactivity disorder,ADHD)汉族患儿与儿茶酚-O-甲基转移酶(catechol-O-methyltransferase,COMT)基因第158位密码子G→A点突变所引起的缬氨酸→甲硫氨酸(Val158Met)的错义突变多态性的关系.方法采用聚合酶链反应-限制性片段长度多态性技术,分析了117例符合DSM-Ⅳ诊断标准的上海汉族ADHD患儿与105例正常健康对照组的COMT基因的Val158Met多态性位点频率.结果 ADHD组的A等位基因频率为25.21%,而对照组为23.81%,两组差异无显著性(χ2=0.5197, P＞0.05). COMT各基因型的分布频率在ADHD和对照组之间的差异也无显著性(P＞0.05).结论汉族儿童注意缺陷多动障碍COMT基因Val158Met多态性可能与ADHD无关联.     

注意缺陷多动障碍与儿茶酚-O-甲基转移酶基因的关联分析

目的：分析COMT基因多态性与ADHD的关联;寻找ADHD的易感基因。方法：采用PCR-RFLP技术,检测54名ADHD患者及其父母（n=82）和正常对照者（n=30）COMT基因Val158Met多态性的基因型和等位基因频率,运用病例对照研究和核心家系的关联分析（HRR和TDT）方法分别进行分析。结果：Val158Met多态性的各基因型和等位基因频率在ADHD组与对照组以及核心家系中的分布差异均无显著性（均P〉0．05）。注意缺陷为主型患儿COMT基因的G／G型频率和G等位基因频率明显高于混合型的（P〈0．05）,A等位基因与ADHD的某些临床症状如注意问题、违纪行为、攻击行为等相关。结论：（1）COMT基因可能与ADHD缺乏关联。仅起微效基因的作用：（2）COMT可能与ADHD临床亚型或临床症状有关。     

脑源性神经营养因子Val66Met基因多态性与首发精神分裂症临床特征的关联研究

目的 探讨脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)基因Val66Met多态性与首发精神分裂症临床特征的关联性.方法 应用TaqMan荧光探针技术对135例首发精神分裂症患者及483名正常对照者进行基因分型;采用阳性与阴性症状量表(positive and negative syndrome scale,PANSS)评估精神分裂症患者临床特征.结果 精神分裂症患者组与正常对照组BDNF Val66Met基因型及等位基因分布频率的差异具有统计学意义(P＜0.01);Met/Met基因型患者的PANSS总分、焦虑(抑郁)因子分及认知损害因子分均高于Val/Val和Val/Met基因型患者,差异有统计学意义(P＜0.01).结论 BDNF基因Val66Met多态性可能与精神分裂症的发病有关;首发精神分裂症患者中Met/Met基因型者临床症状可能更重.     

COMT基因多态性与ADHD患儿青春期预后的关联分析

目的: 探讨儿茶酚-O-甲基转移酶(COMT)基因Val108/158Met(rs4680)多态性对中国汉族男性注意缺陷多动障碍(Attention deficit hyperactivity disorder,ADHD)患儿青春期预后的影响.方法: 对77名基线时符合美国<精神障碍诊断与统计手册(第4版)>(DSM-IV)诊断标准的中国汉族ADHD男性患儿进行青春期的随访,以定式访谈方法按同样诊断标准对随访组确定诊断,并检测COMT基因Val158Met多态性.采用卡方检验对ADHD不同预后结局进行COMT基因Vall58Met多态性等位基因频率的比较.结果: 77名患者中,41人(53.25)ADHD无缓解,36人(46.8%)达到不同程度的缓解,缓解组中16人(20.8%)满足功能缓解,7人(9.1%)症状缓解,13人(16.9%)综合征缓解.各种缓解表型与无缓解型的COMT基因Val158Met等位基因频率差异无统计学意义.结论: COMT基因Val158Met多态性对ADHD男性患儿青春期预后无关联,但尚需进一步扩大样本量进行验证.     

精神分裂症患者听觉惊跳反射抑制与儿茶酚-O-甲基转移酶基因Val158Met多态性的相关性

目的:探讨精神分裂症患者儿茶酚-O-甲基转移酶(COMT)第158位密码子从缬氨酸到蛋氨酸的多态性(Vall58Met)与听觉惊跳反射抑制(PPI)的关系。方法:选取符合美国精神障碍诊断与统计手册第4版(DSM-IV)的精神分裂症患者178例,正常对照190例,使用SR-HLAB惊跳反射监控系统测查听觉惊跳反射,其分析指标包括:惊跳反射的反应波幅(SR);惊跳反射的适应性(HAB);时间间隔(LI)为30 ms、60 ms、120 ms时的听觉刺激惊跳反射弱刺激抑制(PPI30%、PPI60%、PPI120%);应用聚合酶链反应和限制性片段长度多态性的方法,分析精神分裂症组与对照组COMT Vall58Met基因型与等位基因分布频率。结果:精神分裂症组的波幅(SR)低于对照组[(563±460)mVvs.(695±447)m V,P0.05],适应性(HAB)低于对照组[(32±46)vs.(48±33),P0.01],差异有统计学意义;精神分裂症组与对照组之间PPI差异有统计学意义(F=7.15,P0.05),组与时间间隔的交互作用差异有统计学意义(F=5.57,P0.05),进一步分析发现精神分裂症组的%PPI120低于对照组[(27±5)vs.(35±3),P0.05]。2组间COMT基因型和等位基因分布有统计学意义(χ~2=8.16、11.74,均P0.05)。COMT三种基因型对HAB%的主效应有统计学意义(F=3.07,P0.05);分组和COMT基因型对SR,HAB%,%PPI120的交互作用无统计学意义(F=1.64、2.87、2.26,均P0.05)。结论:COMT基因Vall58Met多态性可能与精神分裂症的适应性有关,但与精神分裂症PPI缺陷可能无关。     

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.