树突状细胞瘤苗治疗颅内胶质瘤的实验研究

目的：观察肿瘤细胞冻融裂解物致敏的树突状细胞(dendritic cell，DC)瘤苗对颅内胶质瘤免疫治疗的效果。方法：通过立体定向的方法接种C6胶质瘤细胞建立Wistar大鼠C6胶质瘤动物模型；自大鼠骨髓分离DC前体细胞，经重组大鼠粒细胞巨噬细胞集落刺激因子(rrGM—CSF) 白细胞介素4(rrIL-4)诱导培养、扩增获得功能性DCs；DCs经反复冻融的C6胶质瘤细胞裂解物体外致敏后皮下回输荷瘤大鼠体内，1次／周，共5次。观察荷瘤大鼠的存活期；以流式细胞仪检测循环血中CD8^ T淋巴细胞水平及体外细胞毒反应；ELISA法检测血清中IL-10及IFN-γ水平。结果：经肿瘤细胞冻融裂解物致敏的树突状细胞免疫治疗的荷瘤大鼠生存期明显延长，外周血中CD8^ T淋巴细胞比例增加；并且治疗组大鼠循环血中IFN-γ水平明显升高，而IL-10水平很低，甚至检测不到。结论：经肿瘤细胞冻融裂解物致敏的DC瘤苗对颅内胶质瘤进行免疫治疗能获得有效的治疗性保护作用。     

SARS-CoV S DNA疫苗诱导特异性T细胞及相关细胞因子的特性研究

目的 小鼠经皮下SARS-CoV S DNA疫苗免疫后，研究其特异性T细胞及相关细胞因子的特性。方法SARS-CoV S DNA疫苗免疫BALB／c小鼠后，获取淋巴细胞悬液。经S抗原多肽刺激后，采用ELISA检测细胞培养上清液中IFN-γ／的水平，利用流式细胞仪在单个细胞水平上检测IFN-γ和IL-2的表达及其关系。结果 当S混合多肽刺激后，DNA疫苗免疫小鼠的淋巴细胞产生大量的IFN-γ，与对照鼠相比差异有统计学意义（P〈0．01）。细胞亚群分析的结果表明，IFN-γ^＋和IL-2^＋的CD4^＋T细胞百分率明显高于CD8^＋T细胞。单独产生IL-2的细胞占大多数，其次为IFN-γ和IL-2双阳性细胞，只产生IFN-γ的细胞很少。结论 SARS-CoV S DNA疫苗免疫小鼠后可以诱导抗原特异性CD4^＋和CD8^＋T细胞的产生。     

肿瘤微环境中IL-10限制SOCS1基因沉默的树突状细胞疫苗的抗肿瘤作用

目的观察SOCS1基因沉默的DC疫苗对荷黑素瘤小鼠的抗肿瘤作用及肿瘤微环境中IL-10对该DC疫苗抗瘤作用的影响。方法从小鼠股骨分离骨髓细胞,GM-CSF和IL-4联合诱导DCs分化,然后感染携带沉默SOCS1基因的Len-SOCS1-shRNA慢病毒;用TRP2抗原肽负载沉默SOCS1的DC细胞制备DC疫苗,LPS诱导成熟,流式细胞仪分析DC细胞表面MHCⅡ和CD86的表达,real-time PCR分析该DC细胞的SOCS1、IL-10和IL-12p40表达。用B16细胞或降低IL-10基因表达的B16(B16-IL-10-/-)制备荷瘤小鼠模型,瘤内注射DC疫苗(3×106/只),观察肿瘤生长和荷瘤小鼠生存期。采用不连续梯度离心法分离肿瘤浸润淋巴细胞,流式细胞仪观察CD8+T细胞的分布;并采用微量细胞毒的方法分析CTL活性。结果 Len-SOCS1-shRNA慢病毒感染DC后,可使SOCS1表达下调80%;下调SOCS1表达的DC细胞MHCⅡ和CD86表达有增加趋势,但与对照组DC相比无明显差异;下调SOCS1表达可降低DC细胞的IL-10表达,提高IL-12p40的表达。沉默SOCS1的DC疫苗对B16荷瘤小鼠的生存率没有明显影响,但可显著提高B16-IL-10-/-荷瘤小鼠的生存率(P<0.05)。下调SOCS1表达的DC疫苗不仅可提高B16-IL-10-/-荷瘤小鼠肿瘤浸润CD8+T淋巴细胞数,还可促进CD8+T细胞IFN-γ的分泌及CTL活性。结论沉默SOCS1可提高DC疫苗的活性,但肿瘤微环境的IL-10依然是限制该DC疫苗有效发挥抗瘤作用的因素。     

红景天乙醇提取物调节Lewis肺癌荷瘤小鼠肿瘤浸润T细胞数量并增强抗肿瘤免疫效应

目的探讨藏药红景天(RRL)的抗肿瘤免疫功能。方法将Lewis肺癌荷瘤小鼠随机分为生理盐水组、 500 mg/kg RRL乙醇提取物处理组和10 mg/kg环磷酰胺(CTX)处理组,处理10 d。计算小鼠生存率和肿瘤生长抑制率;流式细胞术检测肿瘤浸润的CD4~+T、 CD8~+ T细胞数量及FOXP3~+调节性T细胞(Treg)占CD4~+CD25~+Treg的比例; ELISA检测荷瘤小鼠血清中白细胞介素2 (IL-2)和γ干扰素(IFN-γ)水平,乳酸脱氢酶(LDH)释放法检测脾细胞毒性T淋巴细胞(CTL)活性。结果 RRL乙醇提取物处理的Lewis荷瘤小鼠生存率显著提高,肿瘤生长受到抑制,肿瘤浸润的CD4~+T细胞和CD8~+T细胞数量增加, FOXP3~+ Treg占CD4~+CD25~+Treg的比例降低。荷瘤小鼠血清IFN-γ和IL-2水平提高,脾脏CTL的杀伤能力增强。结论 RRL乙醇提取物通过调节免疫细胞数量和功能增强抗肿瘤免疫效果。     

肿瘤细胞冻融裂解物上清对凋亡细胞负载的树突状细胞生物学特性的作用研究

目的:探讨Balb/c小鼠骨髓瘤SP2/0细胞冻融裂解物上清对SP2/0凋亡细胞负载的骨髓来源的树突状细胞(DC)的成熟、生物学特性及功能的影响。方法: 采用小鼠重组粒细胞-巨噬细胞集落刺激因子(GM-CSF)和白介素4(IL-4)诱导骨髓来源的DC, 100Gyγ射线辐照诱导SP2/0细胞凋亡, 与未成熟DC共育16-20h;SP2/0细胞冻融裂解物上清和脂多糖(LPS)分别作用于DC48h。采用免疫荧光标记和流式细胞术分析DC表型;[³H]-TdR掺入试验和[⁵¹Cr]释放试验测定DC刺激T细胞增殖和细胞杀伤效应。采用腹股沟皮下DC主动免疫治疗SP2/0荷瘤小鼠, 每间隔14d治疗1次, 共3个疗程, 观察肿瘤生长情况及小鼠生存期。结果:(1)经SP2/0冻融裂解物上清和脂多糖(LPS)诱导凋亡肿瘤细胞负载的DC高表达共刺激分子CD40、CD80、CD86和MHC-Ⅱ分子, 但抗原摄取能力均下降;(2)SP2/0冻融裂解物上清组和LPS组DC体外刺激T细胞增殖和激活CTL能力均高于对照组(P＜0.05);(3)经SP2/0冻融裂解物上清组主动免疫治疗小鼠存活期长于其它各组(P＜0.05)。结论:小鼠SP2/0细胞冻融裂解物上清可诱导凋亡细胞负载的树突状细胞成熟, 能够刺激T细胞增殖和激发肿瘤特异性细胞毒性T淋巴细胞(CTL), 主动免疫治疗可激发荷瘤小鼠体内有效的肿瘤特异性免疫力, 延长荷瘤小鼠生存期。     

呼吸道合胞病毒对致敏小鼠气道炎症和CD8+ T细胞功能的影响

目的观察呼吸道合胞病毒（RSV）对致敏小鼠气道炎症和CD8^＋T细胞功能的影响.方法BALB/c小鼠40只,随机分成4组,分别为磷酸盐缓冲液（PBS）对照组、鸡卵白蛋白（OVA）组、RSV组、OVA/RSV组;应用OVA腹腔注射致敏、OVA气道雾化结合RSV滴鼻激发哮喘;支气管肺泡灌洗液（BALF）作细胞分类计数;酶联免疫吸附试验（ELISA）测定BALF上清中白细胞介素（IL）-4、IL-5、干扰素（IFN）-γ含量;苏木精-依红（HE）染色观察肺病理变化;采用三色光流式细胞分析法测定气管旁淋巴结（PBLN）中CD4^＋、CD8^＋T细胞及细胞内细胞因子IFN-γ、IL-4、IL-5表达与TH2/TH1、Tc2/Tc1比值变化.结果（1）BALF中细胞总数及分类：与OVA组比较,OVA/RSV组细胞总数、嗜酸性粒细胞、淋巴细胞均明显增加（分别P＜0.01）;与RSV组比较,OVA/RSV组细胞总数、嗜酸性粒细胞明显增加（分别P＜0.01）.（2）BALF上清中细胞因子含量：与OVA组比较,OVA/RSV组IFN-γ、IL-4、IL-5含量均明显升高（分别P＜0.01）;与RSV组比较,OVA/RSV组IFN-γ无明显变化,而IL-4、IL-5显著上升（分别P＜0.01）.（3）肺组织病理：OVA/RSV组与其他各组比较气道黏膜增厚,管腔狭窄、收缩,上皮破坏,管壁周围炎症细胞浸润明显加重.（4）PBLN中CD4^＋（WN-γ^＋、IL-4^＋、IL-5^＋）、CD8^＋（IFN-γ^＋、IL-4^＋、IL-5^＋）T细胞各占CD3^＋T细胞百分比及TH2/TH1、Tc2/Tc1比值变化：与OVA组比较,OVA/RSV组CD8^＋（IFN-γ^＋、IL-4^＋、IL-05^＋）T细胞百分比、Tc2/Tc1比值增加（分别P＜0.01）,TH2/TH1比值无明显变化.与RSV组比较,OVA/RSV组CD4^＋（IL-4^＋、IL-5^＋）T细胞、TH2/TH1比值、CD8^＋（IL-4^＋、IL-5^＋）T细胞、Tc2/Tc1比值均明显上升（分别P＜0.01）.结论（1）OVA致敏小鼠RSV感染后可明显加重气道炎症,TH2、TH1型炎症均加强,且以TH2型炎症加重为主.（2）OVA致敏小鼠RSV感染后可引起CD8^＋T细胞数量及功能改变,即由产生IFN-γ^＋为特征的Tc1细胞向产生IL-4^＋、IL-5^＋为特征Tc2细胞转化,并可能与气道内IL-4、IL-5升高及嗜酸性粒细胞的大量募集有关.     

顺铂联合DC疫苗对荷瘤小鼠抗肿瘤作用观察

目的:观察顺铂联合DC疫苗对荷瘤小鼠抗肿瘤作用。方法:用终浓度20μg/ml的顺铂处理体外培养的小鼠黑色素瘤B16或B16-hsp70L1细胞,24小时后,Western blot方法观察HMGB1、hsp70蛋白表达;用顺铂处理的B16或B16-hsp70L1细胞裂解液负载DC,LPS诱导成熟,流式细胞仪分析DCs表面MHCⅠ、ICAM-1、CD86的表达。制备荷瘤小鼠模型,给荷瘤小鼠经腹腔注射顺铂(100μg/只),瘤内注射DC疫苗(3×106/只),观察肿瘤生长曲线、荷瘤小鼠脾脏中肿瘤抗原特异性CD8+T淋巴细胞IFN-γ的分泌及CTL活性。结果:顺铂显著促进B16或B16-hsp70L1细胞HMGB1的表达,对hsp70蛋白表达影响不明显;顺铂处理的B16或B16-hsp70L1细胞裂解液负载DC后,MHCⅠ、ICAM-1及CD86表达率分别为41%、39%、42%和47%、41%、42%;顺铂联合DC疫苗不仅显著抑制荷瘤小鼠肿瘤增殖(P0.05),对荷瘤小鼠脾脏CD8+T淋巴细胞IFN-γ的分泌及CTL活性也有明显的提高。结论:顺铂处理的B16细胞裂解液可诱导DC活化;联合DC疫苗后不仅显著抑制荷瘤小鼠肿瘤生长,对肿瘤特异性免疫应答也具有一定的促进作用。     

模拟失重抑制荷黑素瘤小鼠的T淋巴细胞抗肿瘤免疫功能

目的 研究模拟失重对小鼠T淋巴细胞抗肿瘤免疫功能的影响.方法 小鼠右后肢皮下注射B16细胞建立移植性恶性黑素瘤模型,采用头低位-15°～20°尾吊小鼠模拟失重模型.观察模拟失重对荷瘤小鼠肿瘤体积和生存时间的影响;采用全自动血细胞分析仪和流式细胞仪分别检测模拟失重条件下荷瘤小鼠外周血白细胞、淋巴细胞的变化和T淋巴细胞亚群的变化;采用ELISA法和LDH释放法分别检测模拟失重对肿瘤细胞诱导T淋巴细胞产生IL-2、TNF-α、IFN-γ的水平和肿瘤特异性CTL对肿瘤细胞杀伤活性的影响.结果 与对照组相比,模拟失重组荷瘤小鼠肿瘤生长速度加快,生存期缩短,外周血淋巴细胞总数降低,淋巴细胞比例降低,CD3+、CD4 +/CD3+、CD8+/CD3+T淋巴细胞所占比例降低,丝裂原诱导的脾脏T淋巴细胞增殖能力降低(P＜0.05或P＜0.01).模拟失重条件下,肿瘤细胞诱导产生的细胞因子IL-2、IFN-γ和TNF-α水平降低,肿瘤特异性CTL对肿瘤细胞的杀伤活性降低(P＜0.05或P＜0.01).结论 模拟失重抑制小鼠T淋巴细胞抗肿瘤免疫功能.     

IL-18BP对急性移植物抗宿主病的影响及机制研究

目的：探讨白细胞介素18结合蛋白（IL-18BP）对小鼠异基因骨髓移植后急性移植物抗宿主病（aGVHD）的影响及作用机制.方法：C57BL/6小鼠随机分为A、B 2组,经致死量^60Coγ射线照射后,经尾静脉移植入BALB/c小鼠骨髓细胞和脾脏细胞.移植后,A组注射NS;B组注射IL-18BP.比较A、B 2组小鼠aGVHD的程度,酶联免疫法（ELISA）测定血清中Th1类细胞因子干扰素-γ（IFN-γ）、白细胞介素2（IL-2）及Th2类细胞因子白细胞介素10（IL-10）、白细胞介素4（IL-4）的浓度.结果：移植后,B组小鼠较A组小鼠的aGVHD程度轻,血清IFN-γ、IL-2的浓度低,血清IL-10、IL-4的浓度高.结论：①IL-18BP可以减轻异基因骨髓移植后aGVHD反应;②IL-18BP促进Th1/Th2平衡向Th2漂移,可能是IL-18BP减轻aGVHD反应的机制之一.     

结核杆菌抗原Ag85B诱导抗黑素瘤免疫应答及其机制研究

目的：探讨Ag85B在诱发抗黑素瘤免疫应答中的作用,以及其用于肿瘤免疫治疗的可行性。方法：经背部皮下接种黑色素瘤细胞株B16建立C57BL/6小鼠荷瘤模型,并分为对照1、2组和实验组。于荷瘤模型建立后,对照1、2组经背部皮下分别接种B16细胞和B16/pcDNA3细胞,实验组背部皮下接种B16/pcDNA3-Ag85B细胞。分别观测3组小鼠肿瘤的体积、生存时间和血清中的IFN-γ及IL-4的含量。研究Ag85B在诱导抗肿瘤免疫应答中的作用。结果：从13d到23d,对照1组和对照2组荷瘤小鼠,肿瘤的平均体积分别从1.1058cm^3和0.9123cm^3增长到7.5983cm^3和5.8746cm^3;而实验组荷瘤小鼠,肿瘤的平均体积由0.5158cm^3增长到1.5080cm^3。对照1组和对照2组荷瘤小鼠的平均生存时间分别为24.1d和24.7d,而实验组荷瘤小鼠的平均生存时间为27.8d。13d内,两对照组和实验组小鼠血清IFN-γ的含量均有所上升（对照1组、对照2组和实验组分别上升至26.3ng/L、23.0ng/L和25.2ng/L）,随后两对照组小鼠血清IFN-γ的含量均呈下降趋势（对照1组和对照2组分别下降至19.3ng/L和18.3ng/L）,而实验组小鼠血清IFN-γ的含量则呈上升趋势（上升至46.5ng/L）。13d内,两对照组和实验组小鼠血清IL-4的含量均有轻微升高,随后逐渐下降,但3组小鼠血清IL-4含量的变化差异不明显。结论：接种B16/pcDNA3-Ag85B细胞的实验组小鼠血清中IFN-γ的含量明显增高,并可抑制荷瘤小鼠体内肿瘤的生长,延长荷瘤小鼠生存的时间。     

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.     

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.     

'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.     

Hypo- und Hypermagnesämie aus kardiologischer Sicht

Zusammenfassung Eine Reihe pathologischer Zustände bedingen Magnesiummangel. Zustände mit Hypermagnesämie sind ebenfalls bekannt, doch wesentlich seltener. Für den Kardiologen beachtenswert ist, daß unter Therapie mit bestimmten Diuretica bei Herzinsuffizienz, bei Herzinfarkt, Kardiomyopathie, Digitalisintoxikation und bestimmten Herzrhythmusstörungen Hypomagnesämie beobachtet wurde. Leider kann in der klinischen Routine nur ein extracelluläres Magnesiumdefizit durch Serumbestimmungen gemessen werden; über Magnesiummangel einzelner Organe kann nichts ausgesagt werden. Hinweise für Magnesiummangel geben aber neben der Messung des Serumspiegels Anamnese, klinischer Befund, bestimmte EKG-Veränderungen wie auch evtl. Hypokalämie, ein Zustand, bei dem sich oft — besonders bei Aldosteronismus — parallele Veränderungen zeigten.Tierexperimente deuten darauf hin, daß infarktähnliche Läsionen unter Magnesiummangel entstehen, doch ob Herzinfarkt beim Menschen durch Magnesiummangel ausgelöst werden kann, ist noch ungeklärt. In Leichenherzen zeigte sich im Infarktgebiet neben Calciumakkumulation signifikanter Magnesiumverlust, wobei unklar blieb, ob sich Ursache oder Folge des Infarktes widerspiegelten. Falls ein ursächlicher Zusammenhang besteht, ist er im Myokardstoffwechsel selbst zu suchen, wie bei der Alkoholkardiomyopathie, wo myokardialer Magnesiummangel zumindest als pathogenetischer Teilfaktor anerkannt wird. Andererseits versucht man aber auch Beziehungen zwischen Atherosklerose, Blutgerinnung und Hypomagnesämie herzustellen, in der Meinung, daß Magnesiummangel auch über den coronaren Pathomechanismus des Herzinfarktes wirken könnte. Sicher scheint, daß gewisse EKG-Veränderungen und Herzrhythmusstörungen durch einen irritierten Magnesiumhaushalt bedingt sein können, da sie bei Gabe bzw. Entzug von Magnesium verschwinden. Daß Magnesiummangel die Glykosidtoleranz verringert, wird tierexperimentell bestätigt. Unter Hypomagnesämie bewirkt Acetylstrophanthidin eher und länger Rhythmusstörungen als ohne, außerdem lassen diese sich durch Magnesiumgaben eliminieren. Da in gewissen Fällen spontane und digitalisinduzierte Herzrythmusstörungen durch Magnesiuminjektionen beseitigt wurden, scheint Magnesium als Therapeuticum angebracht. Einsatz verschiedener Magnesiumsalze bei Angina pectoris, degenerativen Herzerkrankungen und Herzinsuffizienz ohne geprüften und offensichtlich gestörten Magnesiumhaushalt ist fragwürdig, weil keine eindeutigen klinischen Erfolgsbeweise vorliegen. Immerhin mag es aber larvierte, durch Serumbestimmungen nicht erfaßbare Mangelzustände geben. Allgemein erscheint es aus kardiologischer Sicht ratsam, den Magnesiumhaushalt zu überwachen und in entsprechenden Fällen auszugleichen, um möglichen Myokardläsionen oder fatalen Herzrhythmusstörungen entgegenzuwirken.     

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.