山东汉族人群中发现一例罕见的血小板特异性抗原HPA-10bw等位基因

目的:探讨山东汉族人群血小板抗原系统10(HPA-10w)的基因多态性,补充本地区血小板供者库数据。方法:应用PCR特异性引物分析法(PCR sequence specific primer)和直接测序方法对山东地区汉族血小板捐献者样本进行HPA-10等位基因分型。结果:在1401例山东汉族机采血小板捐献者中,发现一例...     

两例罕见的血小板抗原HPA-21bw等位基因报告

目的:调查中国人群人类血小板抗原HPA-21w多态性.方法:采用聚合酶链反应-序列特异性引物法(PCR-SSP)基因分型技术,对广州汉族血小板献血者进行HPA-21w基因分型,并使用PCR扩增HPA-21w基因片段,进行DNA测序验证.结果:在200例受检者中发现2例HPA-21 a/b杂合子个体,DNA测序表明GPIIIa编码基因1960位G→A,导致GPIIIa膜糖蛋白第628位谷氨酸被赖氨酸所取代,产生HPA-21 bw抗原特异性.中国人群HPA-21 bw的等位基因频率为0.50％.结论:在中国人群首次检出HPA-21 bw等位基因,提示在血小板同种免疫症的诊断和血小板输注治疗中,该抗原具有免疫学意义.     

汉族人群血小板同种抗原HPA-3、HPA-9w多态性分布

目的研究我国不同汉族人群血小板同地区种抗原HPA-3、HPA-9w多态性。方法采用聚合酶链反应-序列特异性引物(polymerase chain reaction-sequence specific primers,PCR-SSP)技术对1000名来自不同省份汉族无关献血者进行HPA-3、HPA-9w抗原基因分型。结果在调查的1000名汉族人群中HPA-3a、HPA-3b基因频率分别为0.5935和0.4065,HPA-9全为a/a纯合子。经χ2检测,符合Hardy-Weinberg平衡。不同地区汉族人群之间比较,广东省与陕西、黑龙江、浙江、云南、江苏5省的HPA-3多态性分布差异有统计学意义,其余省份之间多态性分布差异无统计学意义。中国汉族人群与越南人、澳大利亚人HPA-3的多态性分布差异有统计学意义。结论在随机输血中供受者HPA-3抗原不配合比例达0.3661,这为研究同种免疫血小板减少症、开展血小板同型输注提供了理论基础。     

中国山东地区汉族人群血小板特异性抗原-15基因多态性分析

目的:分析山东地区汉族人群血小板特异性抗原(HPA)15基因多态性分布特点。方法:采用PCR-序列特异性引物(PCR-SSP)技术对108例无血缘关系汉族人进行HPA-15基因分型,计算等位基因频率、基因型频率并与其他种族、地区人群相关资料比较。结果:等位基因HPA-15a和HPA-15b分布频率分别为0.5139和0.4861;基因型HPA-15a15b、-15a15a、-15b15b频率依次为0.2407、0.2130、0.5463;HPA-15基因分布与越南、德国、奥地利人近似,而与印地安人差异有显著性(P<0.05)。结论:山东地区汉族人HPA-15基因存在多态性,并具有明显的种族和地域性差异。     

黑龙江省满族人群血小板抗原1～17系统基因多态性的研究

目的 探讨黑龙江省满族人群人类血小板抗原(HPA)1～17系统基因多态性及其表达频率,建立HPA基因型资料库.方法 选择101例满族的健康无血缘关系的人群为研究对象,采用PCR-SSP技术,对HPA1～17共17个抗原系统34个等位基因进行分型,分别计算其基因频率、基因型频率.结果 黑龙江省满族人群HPA-1a、2a、3a、5a、6a、15a基因频率分别是0.99505、0.940595、0.549505、0.99505、0.9802、0.445545,HPA-4a、7a～14a、16a和17a均为1.0;HPA-1b、2b、3b、5b、6b、15b基因频率分别是0.00495、0.059405、0.450495、0.00495、0.0198、0.554455,未检测出HPA-4b、7b～14b、16b和17b.调查和分析的HPA基因组合型及其频率发现满族人群HPA基因有22种组合型,其中仅有3种基因组合型频率＞10％(42.57％),另外19种基因组合型的频率均＜10％(57.43％).黑龙江省满族HPA基因频率与黑龙江省汉族相比,HPA-3a、3b基因频率差异具有统计学意义(P＜0.05).结论 黑龙江省满族健康人群HPA1～ 17基因频率的分布与汉族人群相比有相似之处,也有本民族的自身特点.HPA-3,15系统具有高度多态性,在随机血小板输注中,供受者HPA-3、HPA-15系统不配合的机会分别为37.25％、37.20％,易发生血小板不配合而造成的同种免疫,是HPA配合性输注关注重点.     

海南岛黎族人血小板1～17抗原系统基因多态性研究

目的 调查海南岛黎族人群血小板抗原基因(human platelet alloantigens,HPA)1～17等位基因多态性,分析不同民族的差异,评估其在随机输血中供受者HPA不配合比例,为黎族人群临床血小板输注提供实验依据.方法 采用聚合酶链反应-序列特异性引物方法 对180名黎族人HPA-1～17抗原系统34个等位基因分型.结果 黎族人HPA的等位基因频率分别为:HPA-2a:0.9972,-2b:0.0028,-3a,0.4889,3b:0.5111,5a:0.9667,-5b:0.0333,-6a:0.9972,-6b:0.0028,-15a:0.4250,-15b:0.5750,其余HPA-1、-4、7、-14、-16、-17系统未检出相应HPA-b等位基因.结论 本研究结果 揭示了黎族人HPA-1～17基因型和等位基因频率分布概况,提示黎族人HPA基因频率分布具有黎族人独有的特点.在随机血小板输注中,HPA不配合的机会依次为:HPA-3为37.49%、HPA-15为36.93%、HPA-5为6.23%,只需检测供、受者HPA-3、-5、-15基因相合,就可基本达到血小板匹配性输注.     

海南岛黎族人血小板1～17抗原系统基因多态性研究

目的 调查海南岛黎族人群血小板抗原基因(human platelet alloantigens,HPA)1～17等位基因多态性,分析不同民族的差异,评估其在随机输血中供受者HPA不配合比例,为黎族人群临床血小板输注提供实验依据.方法 采用聚合酶链反应-序列特异性引物方法 对180名黎族人HPA-1～17抗原系统34个等位基因分型.结果 黎族人HPA的等位基因频率分别为:HPA-2a:0.9972,-2b:0.0028,-3a,0.4889,3b:0.5111,5a:0.9667,-5b:0.0333,-6a:0.9972,-6b:0.0028,-15a:0.4250,-15b:0.5750,其余HPA-1、-4、7、-14、-16、-17系统未检出相应HPA-b等位基因.结论 本研究结果 揭示了黎族人HPA-1～17基因型和等位基因频率分布概况,提示黎族人HPA基因频率分布具有黎族人独有的特点.在随机血小板输注中,HPA不配合的机会依次为:HPA-3为37.49%、HPA-15为36.93%、HPA-5为6.23%,只需检测供、受者HPA-3、-5、-15基因相合,就可基本达到血小板匹配性输注.     

海南岛黎族人血小板1～17抗原系统基因多态性研究

目的 调查海南岛黎族人群血小板抗原基因(human platelet alloantigens,HPA)1～17等位基因多态性,分析不同民族的差异,评估其在随机输血中供受者HPA不配合比例,为黎族人群临床血小板输注提供实验依据.方法 采用聚合酶链反应-序列特异性引物方法 对180名黎族人HPA-1～17抗原系统34个等位基因分型.结果 黎族人HPA的等位基因频率分别为:HPA-2a:0.9972,-2b:0.0028,-3a,0.4889,3b:0.5111,5a:0.9667,-5b:0.0333,-6a:0.9972,-6b:0.0028,-15a:0.4250,-15b:0.5750,其余HPA-1、-4、7、-14、-16、-17系统未检出相应HPA-b等位基因.结论 本研究结果 揭示了黎族人HPA-1～17基因型和等位基因频率分布概况,提示黎族人HPA基因频率分布具有黎族人独有的特点.在随机血小板输注中,HPA不配合的机会依次为:HPA-3为37.49%、HPA-15为36.93%、HPA-5为6.23%,只需检测供、受者HPA-3、-5、-15基因相合,就可基本达到血小板匹配性输注.     

血小板特异性基因(HPA-1～17)在广州地区人群中分布的多态性研究

目的:调查在广州地区人群中HPA-1～17基因的多态性及其表达频率。方法:采用序列特异性引物-聚合酶链反应(SSP-PCR)对500名健康的血小板捐献者的HPA基因进行分型。结果:广州地区健康的血小板捐献者中表达出HPA-a基因中的1a～17a基因;各基因独立的分布频率中,HPA-1a(99.8%)、2a(99.85%)、3a(56.3%)、4a(99.9%)、5a(98.8%)、6a(98.6%)、15a(55.1%),HPA-7a～14a、16a、17a均为100%。仅表达HPA-b基因中的1b、2b、3b、4b、5b、6b和15b,分布频率为HPA-1b(0.2%)、2b(0.15%)、3b(43.7%)、4b(0.1%)、5b(1.2%)、6b(1.4%)、15b(44.9%);未表达HPA-7b、8b、9b、10b、11b、12b、13b、14b、16b和17b;说明HPA-1a～17a和HPA-3b、15b在广州地区为高频率基因。在与中国汉族不同地区HPA基因多态性分布的比较分析中发现,广州地区人群中HPA基因频率与北京地区人群的差异较明显;在与部分国家民族人群的比较分析中发现,广州地区人群中HPA基因频率与欧洲、美国、英国和埃及人群有较明显差异,而与日本和泰国人群的差异较小。文中调查和分析了HPA基因组合型及其频率,发现广州地区HPA基因有40种组合型,其中仅有5种基因组合型频率10%(占25%),另外35种基因组合型的频率均9%(占75%)。结论:数据提示广州地区人群中HPA基因遗传距离较接近。HPA基因表达和分布频率在中国汉族人群中存在南北差异。与不同亚洲以外的种族和国家之间亦表现出基因表达和分布的差异。HPA基因多态性研究数据有利于指导地区性血小板供者库库容的设计,配合临床开展选择适合性血小板输注,避免同种免疫造成的血小板输注无效,且对开展HPA相关临床研究具有重要意义。     

广州汉族配偶人类血小板抗原基因分型的调查

目的调查配偶之间人类血小板抗原（HPA）的不配合率并评估其在新生儿同种免疫性血小板减少症（NAIT）中的作用。方法采用SSP法对200对广州汉族配偶进行了HPA-1～-16基因分型。结果配偶双方HPA-1～-6及HPA-15均在同-HPA位点具有不同基因型．HPA-7～-14及HPA-16均为a／a纯合子。得到HPA-1～-16的等位基因频率。HPA．15、HPA-3、HPA-2、HPA-6、HPA-5、HPA-1和HPA一4的不配合率为别为37．42％、37．02％、8．02％、3．84％、2．44％、0．75％和0．24％,其余HPA位点的不配合率为0。结论HPA-5可能是广州汉族人群NAIT最重要的一个HPA系统。HPA-15、HPA-3、HPA-2、HPA-6和HPA-4也分别具有其免疫学意义,这为HPA的抗体检测以及NAIT的诊断治疗提供了实验依据。     

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.     

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.     

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.