北京地区A群和C群脑膜炎奈瑟菌外膜蛋白特征分析

脑膜炎奈瑟菌均表达P1类外膜蛋白,这类蛋白称为PorA蛋白。同时也表达P2或者P3类外膜蛋白,这两类蛋白称为PorB蛋白。PorA和PorB蛋白表面的抗原决定簇是血清亚型和血清型的分类基础。PorA和PorB蛋白二级结构表明,两者分别具有8个暴露在外的环状结构(loopⅠ至Ⅷ)。其中,loopⅠ和Ⅳ是PorA的可变区,而loopⅠ、Ⅴ、Ⅵ和Ⅶ是PorB的可变区,决定菌株血清亚型和血清型的抗原决定簇主要存在于两者的可变区上。我国流脑病例主要是由A群的脑膜炎奈瑟菌引起的,但近年来B和C群     

广东省历年流行性脑脊髓膜炎病原体分子特征分析

目的 了解广东省历年流行性脑脊髓膜炎(流脑)病原体的外膜蛋白编码基因porA和porB基因特征,并确定病原体的优势克隆型.方法 对1967-2007年从流脑患者分离的18株脑膜炎奈瑟球菌(Neisseria meningitidis)进行复苏培养和生化鉴定;通过DNA序列测定分析外膜蛋白编码基因porA、porB特征;对菌株进行多位点序列分型(multilocus sequence typing, MLST),采用PHYLIP软件制作进化树,并与脑膜炎余瑟球菌MIST全球数据库(PubMLST)中的菌株比较,确定优势克隆型菌株,探讨广东省历年流脑疫情分离株的看家基因序列多态性.结果 porA可变区(VR)1的型别以20型为主,VR2的型别在2004年前主要为9型,以后呈现多态性;porB可变区Ⅰ、Ⅳ、Ⅴ、Ⅵ主要分别为4、7、11、10型,2004年后可变区Ⅴ、Ⅵ型别增多;除2007年分离的1株W135菌株外,其余菌株的porB基因均无Ⅶ、Ⅷ可变区.在7个看家基因中,abcZ等位基因多态性最低,pgm最高.广东省历年流行性脑脊髓膜炎分离株2004年前的优势克隆为ST-5克隆系,自2004年开始出现高致病性ST-4821克隆系,2007年首次出现高致病性ST-11克降系.结论 广东省历年脑膜炎奈瑟球菌分离株的外膜蛋白编码基冈呈现多态性特征,分离株为多克隆系并存,近期以高致病性克隆系为主.     

两株B群流脑菌LOS抗原性的研究

在对我国自７０年代以来从病人和带菌者中分离的９１株Ｂ群脑膜炎奈瑟氏菌（Ｎｍ）进行脂寡糖（ＬＯＳ）免疫型分型、外膜蛋白分型／亚型、多位点酶电泳分型等的基础上，挑选了两株具有代表性的菌株３４０７（Ｂ：１５：Ｐ１．２：Ｌ３，７，９：ＲＦＬＰｂ－２０：克隆群Ｉ）和５４２８５２（Ｂ：ＮＴ：Ｐ１．２：Ｌ３，７，９：ＲＦＬＰｂ－２０：克隆群Ｉ）。提取并纯化了它们的ＬＯＳ，通过ＳＤＳ－ＰＡＧＥ分析发现：两株菌的Ｌ     

B群脑膜炎奈瑟菌外膜蛋白作为疫苗候选抗原的研究进展

目前获准上市的流脑疫苗主要有A群、A+C群以及A、C、W-135及Y群的四价混合疫苗,上述疫苗的有效免疫原成分均为脑膜炎球菌的荚膜多糖。而B群脑膜炎奈瑟菌的荚膜多糖因与人类N-乙酰神经氨酸聚合物结构相似,可能产生交叉反应,引起自身免疫病,不适合用作B群流脑的疫苗候选抗原。因此,研究者把焦点转向B群脑膜炎奈瑟菌外膜蛋白,目前报道的B群流脑疫苗外膜蛋白候选抗原主要包括fHBP、NspA、NHBA、NhhA、NadA、GNA1946、GNA1162、NMB0315等。本文就上述外膜蛋白作为B群流脑疫苗候选抗原的最新进展作一综述。     

铜绿假单胞菌随机扩增多态性DNA指纹法基因分型研究

建立了铜绿假单胞菌（ＰＡ）随机扩增多态性ＤＮＡ（ＲＡＰＤ）指纹图基因分型方法，并应用于流行病学相关或不相关的７５个ＰＡ菌株的基因分型。分型率为１００％。３２株新生儿暴发感染菌株，可分成４个血清型和５个ＲＡＰＤ谱型，其中２５株属于同一谱型。在８例患者的垂直追踪菌株中，除有１例其第１和第３个分离株的血清型和ＲＡＰＤ谱型均相同，但与第２个分离株的血清型和ＲＡＰＤ谱型不同外，其余７例前后菌株的谱型相同。１３株散发菌株可分成３个血清型和１０个ＲＡＰＤ谱型；１２株流行病学无关菌株的ＲＡＰＤ谱型均不相同。本研究结果表明，ＲＡＰＤ指纹图基因分型法具有分型率高、分辨力强、比较快速简便等优点，并且不需要已知核酸序列，是在分子水平上对微生物感染的病原学、发病机理及流行病学研究的较理想的方法。     

韶关市2009—2011年健康人群C群脑膜炎奈瑟菌血清杀菌力抗体检测结果分析

目的了解韶关市健康人群血清C群脑膜炎奈瑟菌杀菌力水平,以评价健康人群对C群脑膜炎奈瑟菌的保护水平。方法2009—2011年,每年随机抽取8个年龄组健康人群血清共计811份,采用血清杀菌力试验检测血清中杀菌力抗体水平。结果811份健康人群血清中C群脑膜炎奈瑟菌杀菌力抗体总阳性率为25．40％,总保护率为23．06％,GNT为l：5．13,95％置信区间1：4．57～1：5．89。结论韶关市健康人群对c群脑膜炎奈瑟菌的传染有易感性,年龄越低其对C群脑膜炎奈瑟菌的抵抗力越弱,应加大对A＋C群流脑疫苗宣传力度,普及适龄儿童A＋C群流脑疫苗的免疫接种。     

A、C群脑膜炎奈瑟球菌免疫原性及毒性和传代稳定性研究

目的 为保证疫苗质量的一致性和可控性,对A、C群脑膜炎奈瑟球菌结合疫苗生产用菌株CMCC(B)29201和CMCC(B)29205株进行毒性和抗原传代稳定性研究,并对30代次菌进行脑腔毒性、免疫原性和产糖质量分析.方法 将A、C群脑膜炎奈瑟球菌工作种子批菌种分别连续传代至30代次并收获3、5、10、15、20、25及30代次菌液,小鼠腹腔注射观察各代次毒性,试管凝集试验和间接ELISA测定各代次抗原性.其中30代次菌液进行小鼠脑腔攻击观察是否引起脑组织病理改变,小鼠皮下免疫观察免疫原性,同时进行发酵培养提取荚膜多糖的质量分析.结果CMCC(B)29201株和CMCC(B)29205株工作种子批菌种的半数致死量(LD50)均≥109个/ml,30代次内的LD50也均≥109个/ml,30代次菌液脑腔毒性测定显示均无病理改变;抗原性试管凝集效价均达1∶320,30代次内的试管凝集效价均达1∶320,ELISA几何平均滴度(GMT)分别为1∶4835和1∶3915,且30代次内的ELISA效价分别为1∶4315和1∶3752以上;30代次菌液的血清杀菌抗体均≥1∶32,用第30代次工作种子批菌种生产的A群和C群脑膜炎奈瑟球菌荚膜多糖各项检定指标均达到国家标准.结论 A、C群脑膜炎奈瑟球菌结合疫苗生产用菌株CMCC(B)29201和CMCC(B)29205株毒性低、抗原性和免疫原性良好,连续传代至30代次仍保持较低的毒性和较好的抗原性及免疫原性,纯化的A群和C群脑膜炎奈瑟球菌荚膜多糖质量符合质控要求.     

H因子结合蛋白作为B群流脑候选疫苗抗原的研究进展

脑膜炎奈瑟菌表面蛋白H因子结合蛋白(f HBP),是脑膜炎奈瑟菌的外膜蛋白和重要毒力因子,能与补体调节蛋白H因子结合。结合于脑膜炎奈瑟菌表面的H因子,能下调补体系统的激活作用,使脑膜炎奈瑟菌逃避补体系统的攻击。f HBP能诱导机体产生高水平的保护性抗体,抗f HBP抗体与f HBP结合后可阻止f HBP与H因子的结合,从而使细菌易于被补体系统杀灭和清除。因此,f HBP已成为B群流行性脑脊髓膜炎理想的疫苗候选抗原之一。现就f HBP的结构、基因的表达与调节、作为B群脑膜炎奈瑟菌疫苗候选抗原的作用、应用策略、安全性和有效性等最新研究进展进行综述。     

制备疫苗用W135/Y群脑膜炎球菌菌种的免疫原性及遗传稳定性观察

目的 为保证生产四价流脑(A、C、W135、Y群)结合疫苗质量一致性和可控性,对分离自国内的W135、Y群脑膜炎球菌CMCC(B)29037株和CMCC(B)29028株进行免疫原性及遗传稳定性观察.方法 将W135/Y群脑膜炎球菌工作种子批菌种分别连续传代至30代,并收获3、5、10、15、20、25及30代次菌液,对各代次菌进行免疫原性、抗原性、生化反应、毒性、毒力测定,并将30代次菌发酵培养后提取荚膜多糖进行质量分析.结果 CMCC(B)29037株和CMCC(B)29028株工作种子批菌种诱导小鼠产生总IgG抗体分别为1∶1114和1∶2229,杀菌抗体水平与IgG抗体间差异无统计学意义;试管凝集效价均达到1∶320,生化检定两菌株均发酵葡萄糖、麦芽糖,不发酵果糖、蔗糖、甘露醇和乳糖;两菌株的LD50均＞109,30代次内各代次菌的免疫原性、抗原性、生化反应和毒性均无差异.30代次菌液脑腔毒性测定显示均无病理改变,用第30代次菌生产的W135/Y群脑膜炎球菌荚膜多糖各项检定指标均合格.结论 分离自国内的CMCC(B)29037株和CMCC(B)29028株为脑膜炎球菌W135/Y群菌株,免疫原性、抗原性好,生化反应合格、安全性良好,连续传至30代次仍保持较好的安全性和免疫原性,30代次菌纯化的W135/Y群脑膜炎球菌荚膜多糖质量符合质控要求,可以用作四价流脑结合疫苗生产株.     

深圳市外来劳务工人A群、C群流行性脑脊髓膜炎抗体水平检测及分析

目的利用横断面基线调查深圳市外来劳务工人血清中A群和C群流行性脑脊髓膜炎（流脑）水平,为外来劳务工人流脑防控提供依据。方法抽取深圳市罗湖区、龙岗区、宝安区3个监测点,每个监测点选择50人份以上,3个监测点共选择1003人,采用间接ELESA法（定量）检测血清中抗A群和C群脑膜炎奈瑟菌抗体效价。结果共检测1003份血清标本,外来劳务工人A群和C群流脑抗体平均滴度分别为10.78μg/ml、2.71μg/ml。A群和C群流脑血清抗体保护率分别为93.7%、64.8%,二者差异有统计学意义（P〈0.01）;不同年龄组、不同籍贯外来劳务工人A群流脑抗体保护率差异均有统计学意义（P〈0.05）。结论深圳市外来劳务工人C群流脑抗体保护率明显低于A群,为了预防可能存在的流脑C群流行和暴发,提示应加强外来劳务工C群流脑多糖疫苗免疫接种。     

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.     

The universal muscular chain reaction,muscle spasm,Torsions, ruptures and extravasations. Chameleons of pathology and some manifestations of simple muscular disorders

Most bodily functions require the coordinated actions of complementary and supplementary paired muscle groups. Where this essential muscular cooperation is lacking, hollow organs may burst and others become literally screwed up, giving rise to many similar spastic diseases such as Torticollis, Twisted ovarian cyst, Torsion of the Testis, Volvulus of the intestines, Varicose Veins, Megacolon, Aortamegaly, Scoliosis, Erb's Palsy, Peyronie's Disease, Main-en-Griffe, Undescended Foot (Pes Cavus), Talipes, Strabismus. Spasm is “panenepidemic” and unclassified examples of Torsion Dystonia and Dyskinesia really are as common as debt and taxes.     

'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.     

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.     

Hypo- und Hypermagnesämie aus kardiologischer Sicht

Zusammenfassung Eine Reihe pathologischer Zustände bedingen Magnesiummangel. Zustände mit Hypermagnesämie sind ebenfalls bekannt, doch wesentlich seltener. Für den Kardiologen beachtenswert ist, daß unter Therapie mit bestimmten Diuretica bei Herzinsuffizienz, bei Herzinfarkt, Kardiomyopathie, Digitalisintoxikation und bestimmten Herzrhythmusstörungen Hypomagnesämie beobachtet wurde. Leider kann in der klinischen Routine nur ein extracelluläres Magnesiumdefizit durch Serumbestimmungen gemessen werden; über Magnesiummangel einzelner Organe kann nichts ausgesagt werden. Hinweise für Magnesiummangel geben aber neben der Messung des Serumspiegels Anamnese, klinischer Befund, bestimmte EKG-Veränderungen wie auch evtl. Hypokalämie, ein Zustand, bei dem sich oft — besonders bei Aldosteronismus — parallele Veränderungen zeigten.Tierexperimente deuten darauf hin, daß infarktähnliche Läsionen unter Magnesiummangel entstehen, doch ob Herzinfarkt beim Menschen durch Magnesiummangel ausgelöst werden kann, ist noch ungeklärt. In Leichenherzen zeigte sich im Infarktgebiet neben Calciumakkumulation signifikanter Magnesiumverlust, wobei unklar blieb, ob sich Ursache oder Folge des Infarktes widerspiegelten. Falls ein ursächlicher Zusammenhang besteht, ist er im Myokardstoffwechsel selbst zu suchen, wie bei der Alkoholkardiomyopathie, wo myokardialer Magnesiummangel zumindest als pathogenetischer Teilfaktor anerkannt wird. Andererseits versucht man aber auch Beziehungen zwischen Atherosklerose, Blutgerinnung und Hypomagnesämie herzustellen, in der Meinung, daß Magnesiummangel auch über den coronaren Pathomechanismus des Herzinfarktes wirken könnte. Sicher scheint, daß gewisse EKG-Veränderungen und Herzrhythmusstörungen durch einen irritierten Magnesiumhaushalt bedingt sein können, da sie bei Gabe bzw. Entzug von Magnesium verschwinden. Daß Magnesiummangel die Glykosidtoleranz verringert, wird tierexperimentell bestätigt. Unter Hypomagnesämie bewirkt Acetylstrophanthidin eher und länger Rhythmusstörungen als ohne, außerdem lassen diese sich durch Magnesiumgaben eliminieren. Da in gewissen Fällen spontane und digitalisinduzierte Herzrythmusstörungen durch Magnesiuminjektionen beseitigt wurden, scheint Magnesium als Therapeuticum angebracht. Einsatz verschiedener Magnesiumsalze bei Angina pectoris, degenerativen Herzerkrankungen und Herzinsuffizienz ohne geprüften und offensichtlich gestörten Magnesiumhaushalt ist fragwürdig, weil keine eindeutigen klinischen Erfolgsbeweise vorliegen. Immerhin mag es aber larvierte, durch Serumbestimmungen nicht erfaßbare Mangelzustände geben. Allgemein erscheint es aus kardiologischer Sicht ratsam, den Magnesiumhaushalt zu überwachen und in entsprechenden Fällen auszugleichen, um möglichen Myokardläsionen oder fatalen Herzrhythmusstörungen entgegenzuwirken.     

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.     

The case for allele‐specific recognition by the TCR

There is a sharp difference in how one views TCR structure–function–behaviour dependent on whether its recognition of major histocompatibility complex‐encoded restriction elements (R) is germline selected or somatically generated. The generally accepted or Standard model is built on the assumption that recognition of R is by the V regions of the αβ TCR, which is not driven by allele specificity, whereas the competing model posits that recognition of R is allele‐specific. The establishing of allele‐specific recognition of R by the TCR would rule out the Standard model and clear the road to a consideration of a competing construct, the Tritope model. Here, the case for allele‐specific recognition (germline selected) is detailed making it obvious that the Standard model is untenable.