再生障碍性贫血外周血和骨髓免疫活性分子变化及临床意义

目的:研究免疫活性分子异常在再生障碍性贫血（AA）发病中的作用及临床意义。方法:应用ELISA测定AA患者骨髓（BM）及外周血（PB）白介素-2（IL-2）、Flt3配体（FL）、可溶性Fas配体（sFasL）的含量变化。结果:AA患者BM及PB中IL-2含量均显著升高;与正常对照相比,该种变化在急性AA尤为明显（P<0.01）,绝大部分患者sFas-L含量增加;FL水平升高尤为显著,达正常水平的25倍以上,且PB与BM的浓度无区别,经治疗有效者IL-2、sFasL和FL明显下降,但sFasL和FL水平不能恢复正常,动态测定表明IL-2、sFas-L和FL的含量与临床疗效密切相关。结论:AA患者PB和BM中免疫活性分子增多是其自身反应性T细胞的异常活化原因之一,定期测定IL-2、sFasL和FL有助于预后判断。     

再生障碍性贫血骨髓及外周血高水平Flt3配体的来源及意义

目的：研究再生障碍性贫血（AA）患者骨髓及外周血高水平FL（Flt3配体）的来源和影响因素。方法：采用常规ELISA法测定AA患者骨髓和外周血FL含量，应用单色和双色免疫荧光标记流式细胞仪分析FL的分泌细胞及其受体Flt3的表达，并观察AA患者淋巴细胞经PHA激发后环胞菌（CyA)对FL分泌的影响。结果：AA患者骨髓和外周血FL含量显著升高，为正常的25倍以上，外周血和骨髓浓度无区别；正常人CD3^ 细胞内贮存有大量FL，而AA患者CD3^ 细胞以膜型FL为主，胞内基本无FL存在；淋巴细胞经PHA活化后可分泌FL，CyA可抑制FL的分泌，结论：AA患者骨髓和外周血FL水平显著升高，主要由CD^＋细胞产生。     

Flt3配体促进再生障碍性贫血患者淋巴细胞向TH1表型分化

目的　探讨Flt3配体 (FL)对再生障碍性贫血 (AA)辅助性T细胞 (TH)分化的影响及与造血功能衰竭的相关性。方法　应用流式细胞仪分析AA患者骨髓及外周血中TH 亚群 ,并观察植物血凝素 (PHA)和白细胞介素 2 (IL 2 )对AA患者TH 亚群影响 ;体外培养研究FL对骨髓和外周血T细胞分化及细胞因子分泌的作用。结果　AA患者骨髓及外周血中TH1细胞比例明显增高 ,且以急性AA更为显著 (P <0 .0 1) ,TH1与TH2细胞比例失衡 ,TH1 TH2比例显著高于正常对照 (2 .1± 0 .8和 1.4± 0 .7,P <0 .0 5) ;AA及正常人淋巴细胞经PHA和IL 2激发后TH1比例并无明显变化 ,而正常人骨髓细胞经与FL共同孵育 10d后 ,培养上清中IFN γ含量增高 ,表型分析提示 ,除TH1细胞比例增加外 ,树突状细胞及自然杀伤细胞阳性率也有明显增加。结论　FL通过树突状细胞诱导淋巴细胞向TH1表型分化 ,是AA造血功能衰竭的原因之一。     

树突状细胞在再生障碍性贫血患者T细胞寡克隆增生中的作用

目的：探讨树突状细胞（Dendritic cell,DC）在再生障碍性贫血（AA）发病中的作用,尤其是对淋巴细胞异常活化的激发作用。方法：采用直接免疫荧光标记流式细胞术分析AA患者骨髓中I型DC的比例;在体外用重组人粒单细胞集落刺激因子（rhGM-CSF）及白介素4（IL-4）诱导外周血单个核细胞成为DC,流式细胞仪检测DC表型,并观察经纯化人脐血CD34^＋细胞抗原,经可溶性人CD40配体（rhsCD40L）激发后对自体T细胞活化和扩增效应;实时定量PCR（RQ-PCR）定量测定DC载荷抗原前后T细胞TCRVβ基因谱的改变。结果：AA患者骨髓中CD1a^＋CD11c^＋细胞和CD11c^＋CD83^＋双阳性细胞比例增多,且以CD11c^＋CD83^＋双阳性的成熟DC为主;外周血来源的DC负载人脐血CD34^＋细胞后对自体淋巴细胞具有明显的刺激作用,并使T细胞TCRVβ基因谱发生取用偏移。结论：DC在AA淋巴细胞寡克隆增殖中起重要作用,但识别的何种抗原尚进一步研究。     

Graves病患者131I治疗前后CD4+CD25+ Foxp3+调节性T细胞的变化

目的:通过对Graves病患者131I治疗前后外周血各淋巴细胞亚群和CD4+CD25+ Foxp3+调节性T细胞含量以及相关基因Foxp3mRNA表达水平的测定,探讨131I治疗方法是否可以通过改变调节性T细胞的含量从而改善Graves病患者的免疫功能异常。方法:采集30例Graves病患者131I治疗前及治疗后1个月的外周血,流式细胞仪检测外周血CD3+、CD3+CD4+、CD3+CD8+、CD3-CD19+、CD3-CD16+CD56+淋巴细胞亚群及CD4+CD25+ Foxp3+调节性T细胞的百分率,Real-TimePCR检测外周血单个核细胞Foxp3mRNA的表达水平。结果:和治疗前相比,Graves病患者131I治疗1个月后外周血CD3+CD4+T细胞和CD3-CD19+B细胞百分率都明显减少(P<0.05),CD3-CD16+CD56+NK细胞百分率明显增加(P<0.05),CD3-CD8+T细胞、CD4+CD25+ Foxp3+调节性T细胞百分率和Foxp3mRNA的表达水平无明显变化。结论:131I不能通过增加调节性T细胞的含量而改善Graves病患者的免疫耐受障碍,但可以通过减少CD4+T和B淋巴细胞的含量和增加NK细胞的含量来控制过度的免疫应答。     

自发性高血压大鼠外周血CD4~+/CD8~+T淋巴细胞比率增加且连接子蛋白40(Cx40)和炎症因子水平升高

目的探讨连接子蛋白40(Cx40)与自发性高血压大鼠(SHR)外周血CD4~+T细胞和CD8~+T淋巴细胞亚群及炎症因子之间的关系。方法采用流式细胞术检测Wistar京都(WKy)大鼠和SHR外周血CD4~+T细胞和CD8~+T细胞及其表面Cx40的表达;采用ELISA检测炎症因子白细胞介素2(IL-2)、γ干扰素(IFN-γ)、IL-4、IL-6表达。结果 SHR收缩压显著高于WKy大鼠,SHR外周血CD4~+T细胞百分率、CD4~+/CD8~+T细胞比率显著高于WKy大鼠,而CD8~+T细胞百分率显著低于WKy大鼠;SHR血清IL-2、IL-4、IL-6水平均显著高于WKy大鼠,IFN-γ无明显差异;SHR外周血CD4~+T细胞和CD8~+T细胞中Cx40表达均显著高于WKy大鼠。结论 SHR外周血CD4~+/CD8~+T淋巴细胞比率增加,且Cx40和IL-2、IL-4、IL-6水平明显升高。     

新型免疫介导骨髓造血功能衰竭小鼠模型的建立及特性分析

目的:通过建立自身免疫介导的再生障碍性贫血(AA)小鼠模型,并分析该小鼠模型的免疫特性,探讨不同类型调节性T细胞(T-regs)在其发生、发展过程中可能的作用。方法:分离雄性B6(C57BL/6)外周淋巴结,并制成淋巴细胞制成悬液,予不同淋巴细胞数经尾静脉注入杂交1代(F1)小鼠(cBy/B6F1),不同时间段处死小鼠,分析外周血及骨髓,观察其造血功能的变化,在此基础上,采用直接免疫荧光标记,流式细胞术检测CD4+T-regs和CD8+T-regs亚群的变化。结果:实验证实注入雄性B6外周淋巴结淋巴细胞,可建立免疫介导的AA小鼠模型;输入淋巴细胞数量是决定受体小鼠骨髓抑制的关键,当输入淋巴细胞数达到10×106/只,可建立AA小鼠模型,淋巴细胞数达到40×106L-1时,受体小鼠因骨髓造血功能衰竭在14～20d内死亡;受体小鼠血细胞下降与雄性B6外周淋巴结淋巴细胞注入时间相关,随着时间的增加,血象呈进行性下降。同时还发现在AA小鼠模型中CD4+和CD8+调节性T细胞亚群有显著变化,与正常F1小鼠相比,受体小鼠CD4+CD25+细胞、CD8+CD25+及CD8+CD28-细胞群明显减少,分别为(1.7+0.9%vs14.4+9.3%)、(2+0.5%vs8.45+0.4%)和(16+0.6%vs39.45+1.2%)。结论:不同亚群在AA的发生、发展过程中起不同作用,CD4+CD25+/CD8+CD25+细胞可能在AA的启动阶段起作用,而CD8+CD28-则可能是小鼠骨髓损伤的细胞亚群。     

ILC2及Tfh的活性与肺腺癌免疫抑制状态的相关性研究

为探讨ILC2和滤泡辅助性T细胞（follicular helper T cell, Tfh）是否协同促进并维持肺腺癌免疫抑制状态,选择肺腺癌患者为研究对象,采用FACS检测患者外周血中ILC2和Tfh的比例;qRT-PCR检测外周血ILC2及Tfh相关因子的表达水平,并对ILC2及Tfh进行相关性分析。结果显示,与对照组比较,肺腺癌患者外周血中ILC2的比例及其相关因子IL-33、IL-25、胸腺基质淋巴细胞生成素（thymic stromal lymphopoietin,TSLP）、IL-13、IL-5及IL-4 mRNA的表达水平均升高（P<0.05）,CD3⁺CD4⁺CXC趋化因子受体5（CXC chemokine receptor 5, CXCR5）⁺T细胞及PD-1⁺CXCR5⁺Tfh的比例升高（P<0.05）,CD3⁺CD4⁺CXCR5^-T细胞的比例下调（P<0.01）,Tfh相关...     

加味玉屏风散对创伤应激小鼠CD4+CD25+调节性T细胞影响的实验研究

目的观察创伤应激状态下及口服加味玉屏风散(玉屏风散加党参)后对小鼠CD4+CD25+Tr细胞影响.方法采用小鼠截肢应激模型,将50只BALB/c小鼠随机分为5组正常对照组(A)、应激对照组(B)、应激+加味玉屏风散高(C)、中(D)、低(E)剂量组.采用流式细胞仪检测小鼠外周血和脾细胞悬液中CD4+CD25-T、CD4-CD25+T、CD4+CD25+Tr的细胞数.结果创伤后72h小鼠外周血及脾细胞悬液中CD4+CD25+Tr细胞比例明显升高(P<0.01),CD4+CD25-T细胞、CD4-CD25+T细胞比例明显降低(P<0.01);给予加味玉屏风散后各组小鼠外周血及脾细胞悬液中CD4+CD25+Tr细胞比例明显降低(P<0.01),CD4+CD25-T细胞、CD4-CD25+T细胞比例明显升高(P<0.01);其中C组与A组比较差异无统计学意义(P>0.05).结论创伤后小鼠CD4+CD25+Tr表达增强,加味玉屏风散可有效抑制其表达.     

慢性乙型肝炎患者外周血T淋巴细胞表面共刺激分子的表达变化及临床意义

目的 探讨T淋巴细胞表面共刺激分子在慢性乙型肝炎(CHB)患者外周血中的表达及其临床意义.方法 选取我院在2013年3月至2014年3月期间收治的126例CHB患者和90例健康对照者作为研究对象,利用流式细胞术和定量PCR检测CHB患者和健康对照者外周血中T淋巴细胞表面共刺激分子CD28、细胞毒性T淋巴细胞抗原(CTLA)-4、程序性死亡分子(PD)-1、T细胞免疫球蛋白粘蛋白分子(Tim)-3及T淋巴细胞亚群的表达变化,并进行比较分析.结果 CHB患者外周血CD3+、CD4+T细胞百分率及CD4+/CD8+比值均低于对照组,而CD8+T细胞百分率高于对照组,组间比较差异具有统计学意义(分别t=4.0868,7.4660,5.5207和3.8160,均P＜0.01);同时,HBV DNV阳性组患者外周血CD3+、CD4+T细胞百分率及CD4+/CD8+比值均低于HBV DNA阴性组,而CD8+T细胞百分率高于HBV DNA阴性组,组间比较差异具有统计学意义(分别t=5.1567,2.7884,2.9987和2.9087,均P＜0.01);此外,CHB患者外周血共刺激分子CD28+及CTLA-4+的表达量均低于正常对照组,而PD-1和Tim-3的表达量高于对照组,差异具有统计学意义(分别t=6.0546,5.0669和6.3006,8.2151,均P＜0.01);同时,HBV DNA阳性高拷贝组患者外周血共刺激分子CD28及CTLA-4的表达量均低于低拷贝组,而PD-1和Tim-3的表达量高于低拷贝组,组间比较差异具有统计学意义(分别t=3.1293,2.7459,2.8661,2.7960,均P＜0.01).结论 外周血T淋巴细胞亚群及其表面共刺激分子的表达水平对于指导CHB患者的临床治疗和判断预后具有一定的临床意义.     

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.     

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.     

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.     

A comparative study of the effects of dimebon,obsidan, finoptin,and cordaron on the functional state of ischemic focus and size of necrotic zone in experimental myocardial infarction

Dimebon, an antihistamine agent, exerts a moderate antianginal effect, improving the function of ischemic focus in the myocardium and decreasing the necrotic zone in experimental myocardial infarction. Dimebon is less active than obsidan, finoptin (except for the size of the necrotic zone), and cordaron. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 12, pp. 642–644, December, 1996     

Effects of sex steroid hormones on lipid peroxidation and glutathione antioxidant system in rat skin

Effects of estradiol and testosterone on the intensity of lipid peroxidation and contents of glutathione redox system components in the dermis and epidermis of rat skin were studied. Only estradiol induced considerable dose-dependent and tissue-specific biphasic antioxidant effects on the skin. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 128, No. 12, pp. 663–666, December, 1999     

Adhesion and growth of CaCo2 cells on surface-modified PEEK substrata

A series of surface-functionalized poly(ether ether ketone) (PEEK) films has been prepared by selective wet-chemistry; they are hydroxylated polymer (PEEK-OH) obtained by reduction, aminated polymer (PEEK-[]-NH2) prepared by coupling a diisocyanate reagent to PEEKOH (PEEK-[]-NCO) followed by hydrolysis, and carboxylated and aminocarboxylated polymers (PEEK-[]-GABA and PEEK-Lysine) resulting from the coupling of aminoacids to PEEK-[]-NCO. The aminated and carboxylated substrata promoted the adhesion and growth of CaCo2 cells in the presence of serum. Fibronectin (FN), an extra-cellular matrix protein, has been covalently fixed and/or adsorbed on various PEEK substrata, in the presence or not of a polymeric surfactant (Pluronic F68). The performances of the FN-grafted substrata (PEEK-[]-FN(1) and PEEK-[]-FN(2)) were significantly higher than those of reference substrata simply coated with FN (PEEK-OH(+FN)(1) and (2), PEEK-[]-NH2(+FN)(1) and (2)), considering the adhesion and spreading of CaCo2 cells in the absence of serum. Moreover, the stability of the adherent cells on the FN-adsorbed substrata dramatically depended on the experimental conditions applied during the PEEK coating with FN.     

THE ODYSSEY – A JUNGIAN PERSPECTIVE: INDIVIDUATION AND MEETING WITH THE ARCHETYPES OF THE COLLECTIVE UNCONSCIOUS

Homer's epic tale of the 20-year return of Odysseus from the Trojan War is investigated with particular reference to Jung's theory of individuation. Odysseus' meetings with 'the anima' in the form of goddesses, sirens and female monsters and his visit to Hades demonstrate the confrontation and humanization of aspects of the archetypal level of the psyche, central to Jung's theories of psychic growth and development. Jung's important ideas of the psychoid level and the transcendent function are explored and linked both to his investigations into medieval alchemy and with findings from contemporary neuroscience. The importance of Jung's constructive method of the interpretation of dreams and myths is shown to be central.