胰岛素B链肽干预对NOD鼠T辅助细胞平衡及胰岛细胞Bcl-2/Bax表达的影响

目的　探讨新生期胰岛素B链肽干预对NOD鼠Ⅰ型糖尿病的预防作用及其机制。方法　采用动物模型NOD鼠 ,新生期胰岛素B链肽干预后检测血糖、尿糖及糖尿病发病率 ;HE染色观察胰岛炎 ;用RT PCR法检测胰腺干扰素γ (IFN γ)、肿瘤坏死因子α(TNF α)、白细胞介素 10 (IL 10 ) ;免疫组化检测胰腺胰岛细胞Bcl 2和Bax表达。结果　新生期B链肽干预组糖尿病发病率为 2 5.0 % ,明显低于对照组 (72 .2 % ,P <0 .0 1) ,且胰岛炎严重程度也明显减轻 (P <0 .0 1)。胰腺TNF α、IFN γmRNA的表达较对照组显著降低 (P <0 .0 1) ;IL 10mRNA的表达增强 (P <0 .0 1)。胰腺胰岛Bcl 2表达明显增强 ,而Bax表达较对照组明显减弱。结论　新生期胰岛素B链肽干预可以预防NOD鼠糖尿病的发生 ,其机制可能与纠正TH1型细胞因子与TH2型细胞因子比例失衡 ,进而上调胰岛 β细胞Bcl 2和下调Bax表达有关     

细胞因子对肾癌细胞株786-0Fas表达及其凋亡的调控

为研究细胞因子对肾癌细胞株 786 0Fas表达以及FasAb介导凋亡的影响 ,单独或联合应用IFN γ ,IFN α ,IL 2 ,TNF α刺激 786 0细胞株 ,并以Fas单克隆抗体 (FasAb )诱导其凋亡。结果发现 ,IFN α、IFN γ均能显著上调 786 0细胞的Fas表达 (P <0 0 1,P <0 0 1)并促进FasAb诱导的凋亡 (P <0 0 1,P <0 0 1) ;IL 2、TNF α对 786 0的Fas表达及FasAb诱导的凋亡均无影响 ;IL 2不能增强IFN α、IFN γ诱导的Fas表达 ,亦不能促进凋亡。TNF α能增强IFN α诱导的Fas表达并促进凋亡 ,但不影响IFN γ诱导的Fas表达及其凋亡。结果表明IFN γ、IFN α可增强肾癌细胞株 786 0的Fas表达 ,并促进FasAb介导的凋亡。但其对FasAb介导凋亡的敏感性并不完全取决于Fas表达水平     

大鼠胰岛β细胞损伤中IL-18的作用研究

新生Wistar大鼠离体胰岛与细胞因子孵育后 ,观测胰岛素释放和一氧化氮 (NO )生成的变化 ,并用逆转录 聚合酶链反应 (RT PCR )观察IL 18受体信号链 (IL 18Rβ )mRNA的表达水平。结果表明 :(1) 0 6 2 5～ 10nmol/L基因重组小鼠 (rm )IL 18孵育胰岛 2 4h后 ,对累积的和葡萄糖刺激的胰岛素释放以及NO生成均无显著效应 ;(2 ) 2 0 0U/ml基因重组大鼠 (rr)γ干扰素 (IFN γ )或 2 5 0U/ml基因重组人 (rh )肿瘤坏死因子 α (TNF α)单独存在对胰岛素释放和NO生成均无明显效应 ,也不能促使 10nmol/LrmIL 18对胰岛素释放和NO生成产生影响 ;(3) 2 0 0U/mlrrIFN γ +2 5 0U/mlrhTNF α或 15pg/mlrhIL 1β均明显促进NO生成和抑制胰岛素释放 ,而 10nmol/LrmIL 18则不影响IFN γ +TNF α或IL 1β的上述效应 ;(4 )即使经IL 1β和 (或 )IFN γ +TNF α或IL 12孵育后 ,大鼠胰岛素瘤 (RIN )细胞或离体大鼠胰岛仍未见IL 18RβmRNA的表达。提示IL 18在细胞因子所致胰岛β细胞损伤中不发挥直接作用 ,原因是IL 18受体在胰岛 β细胞中不表达。     

扩张型心肌病小鼠Th1/Th2细胞亚群及其相关细胞因子的分析

目的:探讨体液免疫在扩张型心肌病发病机制中的重要性。方法:以线粒体腺苷酸转位酶(adeninenucleotidetranslocator,ANT)合成肽免疫液免疫小鼠建立扩张型心肌病动物模型(DCM组) ,运用三色荧光标记流式细胞术检测其脾淋巴细胞中Th细胞亚群分布,ELISA法检测其血清细胞因子IFN γ、IL 4、IL 2、IL 6、TNF α的表达及其抗ANT自身抗体的产生。以不含肽的免疫液免疫小鼠为对照组。结果:DCM组小鼠Th1及Th2细胞亚群较对照组均有增多,以Th2更为显著,且Th1/Th2比值明显低于对照组(P均<0 0 1) ;IL 4、IL 6和TNF α表达明显增高,而IFN γ和IL 2却较对照组明显降低(P均<0 0 1) ;抗ANT自身抗体均为阳性,对照组为阴性。结论:ANT合成肽诱导扩张型心肌病时Th细胞均被激活,Th2细胞介导的体液免疫应答在该病发病机理中起着优势作用。     

系统性红斑狼疮患者外周血CD4~+T细胞细胞因子的检测

本文通过检测系统性红斑狼疮 (SLE )患者外周血中Th1和Th2分泌IFN γ、IL 2、IL 4细胞因子的表达情况 ,探讨Th1/Th2细胞因子水平与SLE的发病关系。采用流式细胞分析法对 4 1例SLE患者和 15例健康志愿者外周血中细胞因子(IFN γ、IL 2、IL 4 )在辅助性T细胞 (CD4 )内的表达进行检测。结果活动期SLE患者Th1细胞因子的表达率较正常人明显下降 (P <0 0 1)。SLE患者Th1细胞因子 (IFN γ、IL 2 )的表达与SLEDAI之间具有明显的负相关性 (P <0 0 5 )。活动期SLE患者Th1细胞因子的表达明显下降 ,SLE患者Th1细胞因子水平与SLEDAI之间呈负相关性     

细胞信号转导介导与日本血吸虫特异性Th1/Th2免疫偏移

分别于小鼠感染日本血吸虫后 0、 4、 6、 8和 12周 ,取脾淋巴细胞体外培养 ,进行细胞信号转导抑制试验 ,观察酪氨酸蛋白激酶 (TPK )、蛋白激酶C (PKC )和磷酯酰肌醇 3 激酶 (PI 3 K )特异性抑制剂 (Tyrphostin 2 5、D sphingosine和Wort mannin )分别特异性抑制和不同组合抑制TPK、PKC和PI 3K后 ,对小鼠脾淋巴细胞经虫卵可溶性抗原 (SEA )诱生IL 2、IFN γ和IL 4的表达水平及对Th1/Th2免疫偏移的影响。结果发现Tyrphostin 2 5对IL 2、IFN γ和IL 4水平的抑制作用均非常显著(P <0 0 1) ,D sphingosine主要影响IL 4的表达 (P <0 0 1) ,而Wortmannin则主要影响IFN γ的表达 (P <0 0 1) ,Tyrphostin 2 5和Wortmannin联合应用可完全阻断IL 2的表达及增强对IFN γ的抑制作用 ,Tyrphostin 2 5和D sphingosine联合应用可完全阻断IL 4的表达。对反映Th1/Th2免疫平衡的Th2分化指数分析表明 ,D sphingosine可使Th2免疫应答优势减弱 ,而Wort mannin则可使Th2免疫应答优势增强。研究结果表明 ,干预细胞信号转导可调节日本血吸虫特异性Th1/Th2细胞因子表达水平及Th1/Th2免疫偏移 ,为探索控制日本血吸虫卵肉芽肿病变的潜在新途径 ,提供了实验依据。     

克鼻敏汤对变应性鼻炎患者血清Th1、Th2细胞因子的影响

目的 :观察克鼻敏汤对变应性鼻炎 (AR)患者血清Th1、Th2细胞因子的影响 ,以探讨其治疗机制。方法 :6 0例AR患者随机分为克鼻敏汤治疗组 (TG)和辛芳鼻炎胶囊对照组 (CG)进行治疗 ;收集治疗前后空腹血清标本 ,用酶联免疫吸附法 (ELISA)对血清中Th1细胞因子IFN γ、IL 2、IL 12、和Th2细胞因子IL 4、IL 5、IL 10进行检测 ;并与健康对照组进行比较。结果 :AR患者血清IL 4、IL 5、IL 10等Th2细胞因子水平明显高于正常 ;而IFN γ、IL 2、IL 12等Th1细胞因子水平明显低于正常(P <0 0 1)。经克鼻敏汤治疗后血清IL 4、IL 5、IL 10等Th2细胞因子水平较治疗前明显下降 (P <0 0 1) ;IFN γ、IL 2、IL 12等Th1细胞因子水平较治疗前有明显增高 (P <0 0 5 )。而对照组无明显变化 (P >0 0 5 )。结论 :克鼻敏汤通过调节Th1和Th2细胞因子的表达 ,纠正失衡的Th1 Th2的细胞因子网络而对变应性鼻炎产生治疗作用     

碘化钠对人甲状腺细胞IL-6、IFN-γ和TNF-α基因表达的影响

本研究以 10 4 M碘化钠 (NaI)刺激单层培养的人Graves病 (GD )甲状腺滤泡上皮细胞 (TEC ) ,采用定性及半定量PCR技术检测刺激前后白介素 6 (IL 6 )、γ 干扰素 (IFN γ )和肿瘤坏死因子 α(TNF α )在细胞中的表达水平。结果表明 :(1) 3例GD组织均含有IL 6及IFN γmRNA ,2例检测到TNF α基因表达 ;(2 )基础状态下 ,3例TEC均表达IL 6基因 ,2例表达TNF α ,而所有样本均无IFN γmRNA ;(3)NaI不能诱导TEC产生IFN γmRNA ,对IL 6mRNA的表达亦无明显影响 ;(4 ) 1例TNF α阴性的TEC样本 ,经NaI刺激后 ,可表达mRNA ,2例原含有TNF α的TEC经刺激后 ,其mRNA的表达水平显著增加。提示碘可通过诱导或增强TEC表达TNF α ,导致自身免疫性甲状腺疾病的发生与发展。     

SARS患者血清细胞因子临床意义探讨

目的　探讨严重急性呼吸综合征 (SARS)患者病情进展的宿主免疫机制。方法　使用流式细胞仪检测急性SARS感染患者 5 0例和正常对照 2 0例的细胞因子 (IL 2、IL 4、IL 6、IL 10、IFN γ、TNF α)。按照疾病预后分成死亡组和治愈组 ,前瞻性设计分析细胞因子在 2组患者中的异同及对病情发展的影响。结果　治愈组与死亡组患者的细胞因子 (IL 2、IL 4、IL 6、IL 10、IFN γ、TNF α)均明显高于正常对照组 ,差异有显著性 (P <0 .0 5 )。治愈组和死亡组比较 :治愈组IFN γ高于死亡组 ,差异有显著性 (P <0 .0 5 ) ,死亡组IL 6、IL 10明显高于治愈组 ,差异有显著性 (P <0 .0 5 )。结论　SARS病毒感染确实引起机体的免疫系统紊乱。功能受损的程度与疾病的预后有一定相关性 ;TH2类细胞因子免疫反应过强 ,TH1类细胞因子免疫反应相对减弱 ,造成的机体免疫自稳平衡失调可能是SARS患者死亡的因素之一     

SARS-CoV感染者血清IFN-γ和TNF-α的动态变化及其意义

目的　探讨SARS患者血清IFN γ和TNF α在SARS冠状病毒感染免疫中的作用。方法　应用酶联免疫吸附法 (ELISA)测定广州地区 2 8例SARS冠状病毒感染患者双份血清IFN γ和TNF α的水平。实验数据采用两样本均数t检验法。结果　 2 8例SARS冠状病毒感染者急性期血清IFN γ和TNF α水平比正常健康对照组明显增高 (P <0 .0 5 ) ;恢复期血清IFN γ水平比正常健康对照组明显增高 (P <0 .0 5 )。感染病程第 1周 ,患者血清IFN γ水平达高峰 ,然后逐渐下降。SARS患者血清TNF α水平在病程第 2周达高峰 ,然后逐渐下降。结论　IFN γ和TNF α在SARS冠状病毒的致病与免疫过程中可能起重要作用     

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.