南京地区婴幼儿杯状病毒感染的分子流行病学研究

目的了解南京地区婴幼儿杯状病毒腹泻的感染状况、临床表现以及分子流行病学特征。方法采集2010年7月至2011年6月南京医科大学附属南京儿童医院5岁以下腹泻患儿粪便标本及儿童保健中心健康婴幼儿粪便标本各428份。采用反转录-聚合酶链反应（RT—PCR）检测杯状病毒,测序确定其基因型别。结果428份腹泻样本中有63份为杯状病毒阳性,检出率为14．72％。其中诺如病毒GⅡ型58例,未检出诺如病毒GI型,札如病毒5例,以诺如病毒GⅡ-42006b型为主要流行株。428份健康对照组标本杯状病毒检出19例,诺如病毒6例,札如病毒11例,2例为诺如病毒GⅡ型和札如病毒混合感染。结论南京地区婴幼儿中存在不同基因型杯状病毒感染,流行毒株以GⅡ-2006b为主。     

江苏省苏州及南京地区2010年婴幼儿腹泻中诺如病毒分子流行病学研究

目的 了解江苏地区婴幼儿腹泻患者中诺如病毒的感染情况,明确该地区诺如病毒的主要基因型别和流行病学特征.方法 收集2010年江苏省苏州市婴幼儿医院及南京市婴幼儿医院疑似病毒性腹泻粪便标本498例,采用荧光定量PCR方法检测粪便中诺如病毒RNA及其基因组别,并对部分阳性标本测序以明确基因型.结果 498份粪便标本中,GⅠ组诺如病毒阳性标本为2例,阳性率为0.4％,GⅡ组诺如病毒为190例,阳性率为38％,对本地区部分诺如病毒阳性标本进行测序,2份GⅠ标本中,一株为GⅠ1型,另一株为GⅠ3型;测序的23份GⅡ标本中21株为GⅡ4型,2株为GⅡ3型.结论 诺如病毒是本省婴幼儿病毒性腹泻的重要病原体,以诺如病毒GⅡ4型为主,同时也存在其他型别的感染流行.     

深圳市儿童秋冬季腹泻诺如病毒检测及基因型分析

目的 了解深圳市儿童秋冬季腹泻中诺如病毒（Nov）的感染状况,并对阳性株进行基因型分析.方法 收集深圳地区多家医院2009年9月至2010年1月腹泻患儿粪便标本307份,通过逆转录-聚合酶链反应（RT-PCR）方法进行诺如病毒核酸扩增,部分阳性标本的PCR产物经纯化、测序,结合GenBank参考株相应核酸序列构建系统进化树并进行基因型分析,采用SimPlot3.5.1对重组株进行分析和鉴定.结果 307份粪便标本中诺如病毒核酸阳性38例,阳性率为12.4％,以6～24个月龄婴幼儿感染为主,占全部病例数的81.6％（31 /38）,感染的发病高峰为10、11月份,占全部病例数的73.7％ （28/38）;26份测序标本中25株属于GⅡ.4型2006b变异体,1株为GⅡ.12/GⅡ.3型重组株.结论 诺如病毒是深圳市儿童秋冬季腹泻的重要病原体,优势流行株为GⅡ.4型2006b变异体,深圳首次检出的诺如病毒重组株为GⅡ.12/GⅡ.3型.     

2011年苏州地区诺如病毒GⅡ组变异株的分子特征研究

目的 了解苏州地区诺如病毒的感染状况及其变异株的分子特征.方法 收集苏州市儿童医院疑似病毒性腹泻粪便标本419例,采用荧光定量PCR方法检测粪便中诺如病毒RNA及其基因组别,并对部分阳性标本测序分析.结果 419份粪便标本中,GⅡ组诺如病毒为122例,阳性率为29％,未检测出GⅠ组诺如病毒,对本地区部分诺如病毒阳性标本进行测序,A区(RdRp区)测序的25份GⅡ标本中25株均为GⅡ.4型;C区(N-S区)测序的26份GⅡ标本中17株为GⅡ.4型,8株为GⅡ.3型,1株为GⅡ.2型;D区(P区)测序的25份GⅡ标本中16株为GⅡ.4型,9株为GⅡ.3型.结论 诺如病毒是本地区婴幼儿病毒性腹泻的重要病原体,以诺如病毒GⅡ.4-2006b亚型为主,此外发现有GⅡ.4-2010亚型(GⅡ.4 New Orleans株)的流行,这是国内首次对该亚型毒株进行报道,同时还检测到部分重组毒株,提示诺如病毒在本地区的遗传变异日趋复杂.     

北京市肠道门诊腹泻患者人杯状病毒感染调查

目的 调查北京地区肠道门诊就诊腹泻患者人杯状病毒的感染情况.方法 收集北京市2011年4月至2012年3月丰台、昌平、怀柔3个区县的肠道门诊就诊腹泻患者450例,采集患者粪便标本,使用逆转录聚合酶链反应法(RT-PCR)对粪便标本进行人杯状病毒RNA检测,对RT-PCR阳性标本的PCR产物进行克隆测序.结果 450例患者标本中68例人杯状病毒阳性(68/450,15.11％).选择其中18例PCR产物进行克隆测序,将获得的序列进行比对分析、构建系统发生树,结果表明,15株为诺如病毒,3株为扎如病毒.其中诺如病毒GⅡ/4型11株(11/18,61.11％),GⅡ/7型1株(1/18,5.56％),GⅡ组未定型3株(3/18,16.67％).结论 人杯状病毒是北京地区肠道门诊就诊腹泻患者的重要病原,主要流行株为诺如病毒GⅡ/4型.     

感染性腹泻疫情中诺如病毒的分子流行病学分析

目的 研究感染性腹泻疫情中诺如病毒的分子流行病学特点.方法 对2008-2010年湖州地区的感染性腹泻疫情标本共119份进行诺如病毒核酸检测,并选取部分阳性扩增产物经序列测定分析诺如病毒的基因型.结果 119份感染性腹泻标本荧光定量PCR检测阳性50份,其中GⅠ型9份,GⅡ型35份,GⅠ和GⅡ混合感染6份.对12份PCR扩增阳性产物进行序列分析显示：5株GⅠ型诺如病毒毒株分属于GⅠ/2和GⅠ/3两种基因型;7株GⅡ型诺如病毒毒株中除1株属于新基因型GⅡb外,其余6株均属于GⅡ/4基因型.结论 诺如病毒是引起湖州地区感染性腹泻疫情最重要的病原菌之一,且湖州地区的诺如病毒存在很高的遗传多样性,同时也存在基因型别的差异.     

2010-2011年兰州地区5岁以下腹泻患儿杯状病毒和腺病毒感染的流行特征

目的 了解兰州地区腹泻患儿中杯状病毒和腺病毒感染的分子流行病学及临床特点.方法 收集兰州大学第一医院2010年7月至2011年6月腹泻患儿粪便标本295份,采用RT-PCR或PCR的方法检测杯状病毒及腺病毒,腺病毒阳性标本利用多重PCR及巢式PCR的方法分型,并对序列进行分析.结果 295份粪便标本中杯状病毒的检出率为13.2％( 39/295),腺病毒的检出率是5.1％ (15/295).分型结果显示:杯状病毒中69.2％为诺如病毒,其余是札如病毒,诺如病毒中以GⅡ-3(13例)为主,其次为GⅡ-4(12例),GⅡ-6(2例);腺病毒主要以F组的41型(10/15)为主,同时还检测到1例A组的31型,2例B组的3型及C组的1例5型和1例6型,两种病毒均主要感染2岁以下儿童,无明显的季节高峰.结论 杯状病毒和腺病毒是2010 -2011年兰州地区病毒性腹泻患儿的重要病原,长期监测具有重要意义.     

分型引物RT-PCR法在杯状病毒分子流行病学研究中的应用

目的：应用分型引物RT-PCR法确定五个地区病毒性腹泻粪便标本中杯状病毒流行型别及感染情况。方法：对五个地区收集的〈5岁病毒性腹泻粪便标本应用针对病毒壳体区域设计的四对引物（GⅠ—SKF／GⅠ-SKR、COG2F／G2-SKR、SLV5317／SLV5749、PreCAP1／82b）进行反转录-聚合酶链反应（RT-PCR）扩增诺如病毒GⅠ和GⅡ组、扎如、星状病毒（Astrovirus）,扩增产物通过1．5％琼脂糖凝胶电泳鉴定。选取部分阳性标本测序研究型别流行特点。结果：本实验从663例标本中共检出单独感染诺如病毒、扎如病毒和星状病毒阳性标本数分别为84、4、11株,同时还发现3株混合感染标本。选取24株诺如病毒阳性标本测序分析发现19株为GⅡ／4型,2株为GⅡ／3型,1株为GⅡ／1型,1株为GⅡ／13型,1株为GⅡ／15型,4株扎如病毒中2株为SGⅠ／1型,1株为SGⅡ／3型,1株为SGⅡ／1型。结论：研究表明杯状病毒是我国婴幼儿腹泻重要病原体,诺如病毒流行株为GⅡ／4型毒株,同时存在其它型别的散在流行;福建、兰州检测到不同型别扎如病毒证明我国存在多种型别的扎如病毒感染。     

一起不明原因感染性腹泻疫情的病原学诊断

目的 明确一起不明原因感染性腹泻疫情的病原体及其基因型别.方法 通过流行病学调查的方法,查明罹患率.对28例疑似病例的28份样本(粪便22份,呕吐物3份,肛拭子3份)采用RT-PCR方法进行诺如病毒核酸检测,并对5份阳性标本的核酸进行序列测定及遗传进化分析.结果 在调查的5694人中,发病160例,罹患率为2.81%.2007年3月7-9日为发病高峰.RT-PCR检测28份样本中,确定14份为阳性.对其中的5株毒株的核酸序列测定及序列遗传进化分析确定为GⅡ/4型诺如病毒,并与2006年诺如病毒流行株2006b同源性最高,为97.9%.结论 本次感染性腹泻疫情由诺如病毒引起.     

分型引物RT-PCR法在杯状病毒分子流行病学研究中的应用

目的:应用分型引物RT-PCR法确定五个地区病毒性腹泻粪便标本中杯状病毒流行型别及感染情况。方法:对五个地区收集的<5岁病毒性腹泻粪便标本应用针对病毒壳体区域设计的四对引物(GI-SKF/GI-SKR、COG2F/G2-SKR、SLV5317/SLV5749、PreCAP1/82b)进行反转录-聚合酶链反应(RT-PCR)扩增诺如病毒GI和GII组、扎如、星状病毒(Astrovirus),扩增产物通过1·5%琼脂糖凝胶电泳鉴定。选取部分阳性标本测序研究型别流行特点。结果:本实验从663例标本中共检出单独感染诺如病毒、扎如病毒和星状病毒阳性标本数分别为84、4、11株,同时还发现3株混合感染标本。选取24株诺如病毒阳性标本测序分析发现19株为GII/4型,2株为GII/3型,1株为GII/1型,1株为GII/13型,1株为GII/15型,4株扎如病毒中2株为SGI/1型,1株为SGII/3型,1株为SGII/1型。结论:研究表明杯状病毒是我国婴幼儿腹泻重要病原体,诺如病毒流行株为GII/4型毒株,同时存在其它型别的散在流行;福建、兰州检测到不同型别扎如病毒证明我国存在多种型别的扎如病毒感染。     

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.