有机锗(Ge-401)对小鼠B淋巴细胞产生抗体的调节

本文报道了有机锗(Ge-401)对Balb/C小鼠产生抗SRBC抗体能力的调节。Balb/C小鼠先经SF_1(人精浆经Sephadex G-100分离得到的第一组分)抑制其免疫功能,然后实验小鼠经腹腔注射Ge-401,每天一次连续7天,对照组小鼠则以等量生理盐水代替。在实验第7天用SRBC免疫小鼠,于免疫后第4天进行溶血空斑试验和血清抗SRBC抗体凝集效价测定。结果表明,Ge-401能明显提高实验组小鼠的溶血空斑数和抗体凝集效价,与对照组相比,p<0.01。提示Ge-401能增强免疫功能抑制状态下小鼠的免疫应答能力——B细胞产生特异性抗体的能力。     

β2糖蛋白Ⅰ免疫小鼠对辅助性T细胞亚群分化的影响

目的探讨β2糖蛋白I(β2GPI)免疫小鼠引起的辅助性T(Th)细胞分化和抗β2GPI抗体产生的机制。方法将健康的BALB/c小鼠随机分为生理盐水组和β2GPI免疫组,每隔2周由尾静脉注射β2GPI或等量生理盐水,共注射2次或4次。采用间接ELISA检测小鼠血清中抗β2GPI抗体的效价;实时荧光定量PCR(qRT-PCR)检测小鼠脾脏细胞GATA结合蛋白3(GATA3)、白细胞介素4(IL-4)、表达于T细胞的T盒(T-bet)、γ干扰素(IFN-γ)、Foxp3的mRNA水平;流式细胞术检测小鼠脾脏淋巴细胞中GATA3阳性细胞和Foxp3阳性细胞的比例。结果 2次免疫后,小鼠血清中出现高效价(1∶100 000)的抗β2GPI抗体,脾脏中Th2特异性指标GATA3、IL-4的mRNA水平和GATA3阳性细胞比例相对生理盐水组升高。4次免疫后,小鼠血清中抗β2GPI抗体效价进一步升高(1∶100 000),脾脏GATA3、Th1细胞特异性标志物(T-bet、IFN-γ)和调节性T细胞特异性标志Foxp3的mRNA水平下调,IL-4的mRNA水平和2次免疫后无明显差异。此外,脾脏细胞中GATA3阳性细胞的比例进一步上调且伴有Foxp3阳性细胞比例的下调。结论β2GPI免疫小鼠引起Th细胞向Th2细胞优势分化,并伴有Th1细胞和调节性T细胞的抑制,有利于抗β2GPI抗体的产生。     

驱虫斑鸠菊对正常小鼠免疫功能的影响

目的探讨驱虫斑鸠菊对小鼠免疫功能的影响,揭示其免疫作用机理.方法利用[3H]-TdR掺入法分别测定了驱虫斑鸠菊对环胞菌素A(Con A)诱导的小鼠脾脏T淋巴细胞和细菌脂多糖(LPS)诱导的B淋巴细胞增殖活性以及脾脏T淋巴细胞分泌白细胞介素-2(IL-2)活性的影响,运用酶联免疫吸附试验测定了驱虫斑鸠菊对小鼠血清中抗体活性的影响;采用流式细胞仪测定脾脏B淋巴细胞表面抗原CD19的表达水平.结果驱虫斑鸠菊的低、中、高3个剂量体内对脾脏T、B淋巴细胞的增殖活性、血清总抗体和针对人A375黑素瘤细胞抗原特异性抗体含量、B细胞表面抗原CD19的表达以及对脾脏T淋巴细胞分泌IL-2活性都具有明显抑制作用.结论驱虫斑鸠菊对机体体液免疫和细胞免疫功能都具有明显抑制作用.     

羧甲基淀粉对小鼠产生抗体和免疫器官的影响

本实验研究了国产羧甲基淀粉(CMS)对小鼠产生 IgE及 IgM抗体和对小鼠胸腺及脾脏重量的影响,结果证明,无论给予或不给予小剂量环磷酰胺(Cy),CMS均能显著或非常显著地抑制小鼠体内诱生抗绵羊红细胞(SRBC)的 IgM直接空斑形成细胞(PFC)数及显著降低小鼠产生抗 SRBC的凝集抗体效价;卵清蛋白致敏的小鼠如加注 Cy能促进IgE产生,但若使用CMS,即使给 Cy仍能非常显著地抑制抗卵清蛋白的 IgE产生。单用CMS能显著增高胸腺的重量,但对脾脏重量无明显影响。机理可能与该药能促进胸腺发育而产生或激活较多的T抑制细胞有关,提示 CMS可能具有免疫调节效应。     

精氨酸单糖苷( AF) 对免疫抑制小鼠免疫功能的影响

目的:研究精氨酸单糖苷(Arginyl-fructose,AF)对环磷酰胺(CTX)诱导的免疫抑制小鼠免疫功能的影响。方法: ICR 小鼠100 只,随机分成5 组,即正常对照组(N),免疫抑制模型组(M),免疫抑制AF 低、中、高剂量组(M-L、M-M、M-H)。试验组连续给药28 d。免疫抑制组,每周前3 天,腹腔注射80 mg/ kg 环磷酰胺,形成免疫抑制。末次给药12 h 解剖后,测定免疫器官指数,AF 对脾淋巴细胞转化及增殖、巨噬细胞吞噬功能、特异性IgG 抗体、血清中TNF-β、IL-2 含量的影响。并通过实时荧光定量PCR 检测TNF-β、IL-2 基因表达的差异。结果:AF 能够显著提高小鼠的胸腺指数和脾脏指数,促进脾淋巴细胞的自然转化与增殖,增强巨噬细胞吞噬功能,显著提高小鼠血清中特异性IgG 抗体含量,可显著提高小鼠血清中TNF-β、IL-2 含量,实时荧光定量PCR 检测结果显示,TNF-β、IL-2 mRNA 能够良好表达。结论:AF 能拮抗CTX 免疫功能低下小鼠的免疫抑制作用。     

黄芪多糖对去T细胞小鼠促进抗体产生机理的探讨

黄芪多糖(APS)100mg/kgx6天 ip 可以增加正常小鼠脾脏重量,而对去胸腺与抗胸腺细胞血清处理过的小鼠(T_x-ATS)的作用明显降低。APS 能够显著提高正常小鼠 SRBC 免疫后脾细胞直接溶血空斑(d-PFC)和间接溶血空斑(i-PFC)数量,但对 T_x-ATS 小鼠不能促进d-PFC 数升高。APS 可以提高 T_x-ATS 小鼠在 LPS 免疫后 d-PFC 数,这个作用同 APS 对正常小鼠 SRBC 免疫后的效应相比显著降低。这些结果提示,APS 促进抗体形成作用机理可能是通过 T 细胞介导的。     

IL-2和GM-CSF表达质粒对pcDNA3/MDC-VP1 DNA疫苗作用的比较

目的:比较IL-2与GM-CSF两种细胞因子对pcDNA3/MDC-VP1 DNA疫苗免疫的免疫增强效果.方法:4～6周龄雄性BALB/c小鼠随机分成pcDNA3组、pcDNA3/MDC-VP1组、pcDNA3/MDC-VP1与pcDNA3/hIL-2混合注射组、pcDNA3/MDC-VP1与pcDNA3/mGM-CSF混合注射组,每组10只.每3周接种1次,共3次.每次接种后的第20天眼眶采血,用微量中和试验(固定病毒-稀释血清法)检测血清中和抗体效价.第3次免疫后3周,每组取3只小鼠脾脏制备淋巴细胞悬液,检测淋巴细胞增殖活性与特异性细胞毒性T淋巴细胞(CTL)杀伤活性.结果:pcDNA3/MDC-VP1+pcDNA3/mGM-CSF组的血清中和抗体滴度明显提高,小鼠脾脏淋巴细胞增殖活性和特异性CTL杀伤活性均有增强.结论:GM-CSF作为本疫苗分子佐剂能诱导小鼠产生较强的体液和细胞免疫,免疫效果优于IL-2.     

小鼠白色念珠菌逆行性肾盂肾炎的免疫功能测定

本实验建立了小鼠白色念珠菌肾盂肾炎模型,并研究了其免疫功能。实验显示,感染30天时,模型动物脾细胞对ConA 刺激的T细胞增殖反应、ConA诱导的IL—2活性均增强。对LPS诱导的B细胞增殖反应增强,以15天最为显著。对SRBC初次抗体应答,在15天、30天时均增强。对白念可溶性抗原的DTH反应性,在15天时升高直到30天时明显。在感染15天时血清特异性凝集效价迅速增高,直至30天仍保持一个高值。     

猪瘟基因疫苗免疫小鼠体液及细胞免疫动态变化研究

目的：探讨猪瘟基因疫苗免疫小鼠后机体产生体液和细胞免疫发生规律，为猪瘟基因疫苗推广应用提供科学依据。方法：应用FACS、MTT法及间接ELISA试验对猪瘟基因疫苗免疫小鼠脾脏及外周血中CD4^ 和CD8^ 淋巴细胞数、淋巴细胞的转化功能及特异的抗猪瘟病毒血清IgG抗体水平等动态变化进行了观察。结果：猪瘟基因疫苗免疫小鼠后脾细胞及外周血淋巴细胞对ConA和LPS均有明显的反应性。CD4^ 和CD8^ 细胞数量在免疫后20天开始反应，32天达到高峰后开始下降。鼠血清特异性猪瘟病毒血清抗体IgG随免疫时间延长而增加。结论：猪瘟基因疫苗免疫动物可诱导机体体液及细胞免疫。     

保元丹对小鼠免疫功能的实验研究

目的 了解保元丹对机体免疫功能的影响。方法 采用Balb/c健康雌性小鼠为实验动物模型,检测了保元丹对淋巴细胞转化值,半数溶血值,抗体生成细胞数,迟发性变态反应以及NK细胞活性的影响。结果 与对照组相比,保元丹高剂量组能显著提高小鼠血清溶血素半数溶血值(P<0.05)。中高剂量能显著提高小鼠淋巴细胞转化值和迟发性变态反应(P<0.05)。低中高3个剂量都能显著提高抗体生成细胞数和NK细胞活性(P<0.01)。结论 保元丹既能增强特异性免疫又能增强非特异性免疫,表明保元丹具有提高机体免疫功能的作用。     

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.     

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.     

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.     

Class II HLA in Georgia Caucasus Tbilisi Georgians and their Mediterranean ancestry: The Usko Mediterranean languages

Georgia (or Sakartvelo in its own language) is a South Caucasus Mts. country with its easternmost part is enigmatically named Iberia, like the Iberian Peninsula, which may refer to rivers “Kura” and “Ebro” or their valleys respectively. Most of their inhabitants speak Georgian which is included within Dene-Caucasian group and Usko-Mediterranean subgroup of languages. The latter includes Basque, Berber, ancient Iberian-Tartessian, Etruscan, Hittite, Minoan Lineal A and others. In the present paper, HLA class II -DRB1 and -DQB1 alleles has been studied and extended haplotypes calculated. Most frequent haplotypes are also of Mediterranean origin (i. e.: (A*02-B*51)-DRB1*11:01-DQB1*03:01, (A*02-B*51)-DRB1*13:01-DQB1*06:03, or (A*24-B*35)-DRB1*01:01-DQB1*05:01) and DA genetic distances show that closest world populations to Georgians are Mediterraneans. Georgians also show common extended haplotypes ((A*02-B*51)-DRB1*11:01-DQB1*03:01, (A*02-B*13)-DRB1*07:01-DQB1*02:01 and (A*03-B*35)-DRB1*11:01-DQB1*03:01) with Svan people, a secluded population in North Georgia mountains. We can conclude that Georgians belong to a very old Mediterranean substratum according to both linguistics (Usko Mediterranean languages) and HLA genetics.     

'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.