寻常型银屑病血清瘦素水平与HLA等位基因相关性研究

目的:研究中国北方汉族人寻常型银屑病(PV)患者血清瘦素(leptin)水平与HLA等位基因的关联性。方法:采用序列特异性引物-聚合酶链反应(PCR-SSP)方法对91例PV患者和102例健康人进行HLA-A、B、Cw、DRB1及DQB1分型,放射免疫分析(RIA)技术测定其血清瘦素水平。结果:(1)PV患者血清瘦素水平(7.63±4.44 ng/ml)较正常对照(5.03±2.72 ng/ml)显著增高(P<0.001);男性及女性PV患者血清瘦素水平分别较男性及女性正常对照显著增高(P=0.004,P<0.001)。(2)北方汉族人PV与HLA-A*010x(Pc=0.039 4)、A*300x(Pc=0.012 9)、B*570x(Pc=0.013 7)、Cw*0602(Pc=0.000 9)、Cw*060x(除外Cw*0602)(Pc<1×10-4)、DRB1*0701/0702(Pc=0.001 2)及DQB1*0201(Pc=0.005 6)等位基因呈正相关,与Cw*040x(Pc=0.018 8)呈负相关。(3)携带HLA-DRB1*15及DRB1*0701/0702等位基因的男性PV患者和携带HLA-A*010x、A*24、Cw*040x、DRB1*15、DQB1*0301等位基因的女性患者的血清瘦素水平均显著增高(P<0.05)。结论:(1)HLA-A*010x、A*300x、B*570x、Cw*0602、Cw*060x(除外Cw*0602)、DRB1*0701/0702及DQB1*0201等位基因可能是北方汉族人PV的易感基因或与易感基因相连锁,HLA-Cw*040x可能是预防PV发病的“保护因子”。(2)PV患者血清瘦素水平显著增高,并与HLA等位基因相关联,提示HLA等位基因和瘦素参与PV发病过程。     

北方汉族泛发型白癜风与HLAⅠ、Ⅱ类等位基因相关性研究

目的探讨北方汉族泛发型白癜风与HLAⅠ、Ⅱ类等位基因的相关性。方法采用聚合酶链反应-序列特异引物技术检测34例北方汉族泛发型白癜风患者及102名健康人的HLA-A、B、Cw、DRB1和DQB1等位基因。结果与正常对照比较，泛发型白癜风患者HLA-A＊30、Cw＊06、DRB1＊07、DQBC＊0201基因频率显著增高，其中家族史阴性患者HLA-A＊30、Cw＊06、DRB1＊07、DQBC＊0201基因频率显著增高，但家族史阳性患者的等位基因频率差异无统计学意义。结论HLA—A＊30、Cw＊06、DRB1＊07、DQB1＊0201等位基因与北方汉族泛发型白癜风相关，可能是其易感基因或与泛发型白癜风的易感基因相连锁。     

济南汉族人群HLA-A、B、DRB1等位基因高分辨多态性分析

目的 分析济南地区汉族人群人类白细胞抗原(human leukocyte antigens,HLA)-A、B、DRB1座位等位基因的高分辨多态性.方法 采用PCR-测序分型(PCR-sequence-based typing,PCR-SBT)对鲁南地区483名无血缘关系的汉族健康个体进行HLA-A、B、DRB1座位高分辨基因分型,采用Arlequin3.5软件计算等位基因频率、单倍型频率,并就常见等位基因与其他人群进行比较.结果 济南汉族HLA-A、B、DRB1座位分别检出27、56和41个等位基因,其中等位基因频率分布最高的分别是A* 11∶01 (0.1615)、B*13∶02(0.1163)和DRB1* 07∶01 (0.1763);最常见的A*-B*-DRB1*单倍型是A*30∶01-B* 13∶02-DRB1* 07∶01 (0.0867).结论 济南地区汉族人群HLA-A、B、DRB1等位基因和单倍型具有较高的多态性.     

汉族HLA-A等位基因与银屑病患者相关性研究

目的 探讨HLA-A等位基因与汉族人银屑病遗传易感性。方法 利用聚合酶链反应-序列特异性引物（PCR-SSP）法，对200例银屑病患者和204例健康人的HLA-A等位基因进行检测。结果 HLA-A*2601-05等位基因与汉族人银屑病呈正相关性（20.25%vs12.25%,RR=1.65,X^2=11.76,P=0.0006,Pc=0.0066),HLA-A*0201-17等位基因与汉族人银屑病呈负相关（4.25%vs9.80%,RR=0.43,X^2=10.26,P=0.0013,Pc=0.0143),HLA-A*2601-05等位基因仅与有家族史银屑病呈正相关（RR=2.04,X^2=12.49,P=0.0004,Pc=0.0044),HLA-A*2601-05等位基因与I型银屑病呈正相关（RR=1.68,X^2=11.67,P=0.0006,Pc=0.0066)。结论 HLA-A*2601-05可能是银屑病的易感基因或与易感基因相连锁。HLA-A*2601-05仅为有家族史银屑病和I型银屑病的危险基因。     

乙肝后肝硬化患者HLA-A、DRB1等位基因多态性研究

目的：了解乙肝后肝硬化患者的HIA-A、DRB1等位基因多态性。方法：用基因芯片分型方法分析比较61例慢性乙肝后肝硬化患者与146例正常人HLA-A、DRB1等位基因的多态性。结果：HLA-A位点中的HIA-A02、11、24与HLA-DRB1位点中的HIA-DRB1*12、09、04为正常人群常见等位基因。乙肝后肝硬化患者组HnA02(43．4％vs29．1％，OR：1．87，P=0．005，95％CI：1．21-2．89)与HLA-DRB1*07(13．9％vs5．1％，OR：3．00，P=0．002，95％CI：1．48-6．07)、HIA-DRB1*08(16．4％vs6．8％，OR：2．67，P=0．003，95％CI：1．40L5．08)、HLA-DRB1*11(12．3％vs5．8％，OR：2．27，P=0．025，95％CI：1．11-4．64)的出现频率较正常对照组明显升高。在HIA-A位点中，乙肝后肝硬化患者组的纯合子比例较正常组有升高趋势，但无统计学意义。结论：HLA-A02与HLA-DRBl*07、08、11可能是乙肝后肝硬化的易感基因。     

黑龙江地区人群HLA-A、B、DRB1 高分辨等位基因及单体型多态性研究

目的:研究中国造血干细胞捐献者资料库黑龙江分库无关捐献者HLA-A、B、DRB1高分辨等位基因和单体型频率分布特征。方法:采用PCR-测序分型技术(SBT)对13 670名随机、无血缘关系、健康的中华骨髓库黑龙江分库造血干细胞捐献者进行HLA-A、B、DRB1高分辨基因分型,利用计数法和最大似然性原理方法分别计算HLA-A、B、DRB1等位基因及单体型频率。结果:共观察到286个HLA等位基因,其中频率0.1的A、B、DRB1座位特异性分别为A*02∶01、A*24∶02、A*11∶01、DR*07∶01、DR*09∶01、DR*15∶01。1 087条A-B单体型中,22条单体型的频率高于0.01,267条单体型呈现显著的正连锁不平衡(ALD0,HF≥1.09×10-4,χ23.84),12条表现为强连锁不平衡(RLD0.80);1 329条B-DRB1单体型中,19条单体型的频率高于0.01,357条单体型呈现显著的正连锁不平衡,18条表现为强连锁不平衡(RLD0.80);4 428条A-BDRB1单体型中,1 348条单体型有意义(频率≥1.09×10-4),17条单体型频率高于0.005。结论:获得黑龙江地区人群HLAA、B、DRB1高分辨等位基因频率和单体型分布数据及相关遗传参数,等位基因和单体型的分布特征接近北方汉族人群,但具有其自身分布特征。     

广州地区献血人群HLA-A、B、DRB1高分辨等位基因及单体型多态性的研究

目的:研究广州地区献血人群HLA-A、B、DRB1等位基因多态性的分布特征。方法:应用序列特异引物-聚合酶链反应(polymerase chain reaction-sequence-specific primer,PCR-SSP)高分辨试剂分型,对广州地区1691名无血缘关系的健康人群HLA-A、B、DRB1进行基因分型。结果:检出HLA-A、B、DRB1等位基因分别有37、76、43种,经统计分析这3个基因座分布均符合Hardy-Weinberg平衡定律(P0.05),A*02:07-B*46:01-DRB1*09:01(4.293%)和A*33:03-B*58:01-DRB1*03:01(3.284%)单体型是广州地区献血人群最常见单体型。结论:广州地区献血人群HLA-A、B、DRB1基因座单体型分布具有高度的遗传多态性且有其自身分布特点。研究获得的HLA-A、B、DRB1基因座单体型分布数据及相关遗传参数资料,为HLA在人类学、免疫遗传学、法医学和其它的组织器官移植方面的应用和科学研究提供和积累了基础资料。     

HLA-A、HLA-B、DRB1等位基因多态性与中国北方汉族肺癌患者遗传易感相关性的研究

目的探讨中国北方汉族人中HLA-A、B、DRB1等位基因与肺癌遗传易感性间的关系。方法采用测序分型技术(sequence-based typing,SBT)技术,对无血缘关系的籍贯为中国北方的140名肺癌患者及483名健康志愿者的HLA-A、B、DRB1基因进行检测。arlequin软件(ver2.000)及SPSS软件进行统计分析。结果 A*2601、B*1518、B*3802、DRB1*0401、DRB1*0402、DRB1*1201在肺癌病人中频率显著性高于正常对照,P值分别为0.021、0.001、0.015、0.021、0.010和0.046,OR值分别为3.513、3.842、2.715、3.512、13.986、1.828;HLA-DRB1*1001、DRB1*1302在肺癌病人中频率显著性低于正常对照,P值分别为0.017和0.014,OR值分别为0.135和0.122。单倍型HLA-A*0207-B*4601-DRB1*0901、HLA-A*0206-B*5101在肺癌病人中频率显著性高于正常对照,P值分别为0.034和0.006,OR值分别为2.348和3.969;单倍型HLA-A*110...     

HLA-DRB1等位基因与吉林地区汉族白癜风和寻常型银屑病相关性研究

目的：探讨HLA-DRB1等位基因与吉林地区汉族白癜风和银屑病的相关性。方法：采用聚合酶链反应-序列特异性引物（PCR-SSP）分型技术,对82例汉族白癜风患者和80例寻常型银屑病患者HLA-DRB1等位基因进行检测,与86名汉族健康人群进行对照。结果：①白癜风患者组HLA-DRB1＊07和HLA-DRB1＊12等位基因频率比对照组明显增高（P〈0.05）;②银屑病患者组HLA-DRB1＊07等位基因频率高于对照组,HLA-DRB1＊01等位基因频率低于对照组（P〈0.05）。结论：①HLA-DRB1＊07和HLA-DRB1＊12等位基因可能是吉林地区汉族白癜风的易感基因或与易感基因相连锁;②HLA-DRB1＊07等位基因可能是寻常型银屑病的易感基因,HLA-DRB1＊01可能为寻常型银屑病的保护性基因。     

青海土族人群HLA-A、B、DRB1基因多态性分析

目的:分析青海土族人群人类白细胞抗原(Human leukocyte antigen,HLA)A、B、DRB1的基因多态性特点。方法:应用聚合酶链反应-直接测序分型(Polymerase chain reaction sequence-based typing,PCR-SBT)法对土族人群中47名健康无血缘关系的个体进行HLA-A、B、DRB1基因座高分辨分型。并将青海土族人群的HLA-DRB1基因与国内其它少数民族人群进行比较。结果:检出HLA-A、B、DRB1的基因型数和等位基因数分别为34、41、42和17、28、30。这3个基因座分布均符合Hardy-Weinberg平衡定律(P>0.05)。且HLA-DRB1基因座等位基因频率分布与蒙古族有相似之处,表现在基因频率较高的DRB1*04,DRB1*07,DRB1*09,DRB1*12等位基因。结论:青海土族人群具有独特的HLA-A、B、DRB1基因频率分布特征,且青海土族HLA-DRB1等位基因频率分布与蒙古族有相似之处。     

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 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.