气道上皮IL-25促进哮喘气道重塑

目的:通过检测白细胞介素-25(IL-25)在嗜酸细胞性哮喘(EA)及非嗜酸细胞性哮喘(NEA)患者的血清、诱导痰及气道上皮中的表达,探讨其在支气管哮喘气道重塑中的作用。方法:选取初诊的哮喘患者55例,健康对照组27例,所有受试者均进行肺通气功能检查,然后采集空腹静脉血及诱导痰。据诱导痰中嗜酸性粒细胞(EOS)的比例将哮喘患者分为EA组和NEA组。采用ELISA检测血清及诱导痰中IL-25的水平,同时对其中的10例EA组患者、10例NEA组患者及10例健康对照者行电子支气管镜气道黏膜活检,免疫组织化学技术分析IL-25在气道上皮的表达,HE染色测量气道重塑的重要指标-基底膜厚度,并行血清及诱导痰中IL-25的水平与基底膜平均厚度的相关性分析。结果:与正常对照组相比,EA和NEA组哮喘患者的肺功能轻度受损。ELISA结果显示哮喘患者血清及诱导痰中IL-25的水平明显高于对照组(P<0.05),而EA和NEA组哮喘患者间差异无统计学意义(P>0.05)。免疫组织化学结果显示哮喘患者气道上皮IL-25的表达明显高于对照组,HE染色显示气道黏膜下的基底膜厚度明显增加(P<0.05)。相关性分析显示哮喘患者血清及诱导痰中IL-25水平与气道黏膜下基底膜平均厚度成正相关。结论:IL-25可能有促进哮喘气道重塑的作用,嗜酸性粒细胞与基底膜厚度无明显相关性,其在哮喘气道重塑中的作用可能是有限的。     

雷公藤对哮喘豚鼠外周血淋巴细胞IL—5,粒细胞—巨噬细胞 …

目的探讨哮喘豚鼠白介素-5(IL-5)、粒细胞-巨噬细胞集落刺激因子(GM-CSF)及CD4+和CD8+T细胞在哮喘发病中的作用及雷公藤的干预作用.方法实验分为哮喘组、雷公藤治疗组(处理组)和对照组,每组各10只豚鼠,采用原位杂交方法检测豚鼠外周血淋巴细胞的IL-5、GM-CSFmRNA表达;应用免疫细胞化学方法检测外周血淋巴细胞CD4+和CD8+的表达.结果哮喘组外周血淋巴细胞IL-5、GM-CSF-mRNA表达均明显高于处理组和对照组(P＜0.01),而处理组和对照组无显著差异.哮喘组外周血淋巴细胞CD4+表达明显高于对照组和处理组(P＜0.01),CD8+表达低于对照组和处理组(P＜0.05).结论哮喘豚鼠外周血淋巴细胞IL-5、GM-CSFmRNA表达增高、CD4+表达增高,CD8+表达降低,而雷公藤甲素可降低外周血淋巴细胞IL-5、GM-CSFmRNA表达,并可提高CD8+表达,降低CD4+表达.表明雷公藤可能在抗哮喘气道炎症中发挥一定作用.     

地塞米松对哮喘小鼠肺组织中GPR43表达的调节作用

目的 研究G蛋白耦联受体43(GPR43)在哮喘小鼠肺组织内的表达,同时探讨地塞米松对GPR43表达的影响.方法 30只BALB/C6小鼠随机分为对照组、哮喘组、地塞米松组,每组10只;卵清白蛋白(OVA)致敏和激发建立哮喘小鼠模型;肺泡灌洗液(BALF)细胞计数;HE染色观察各组气道炎症发生及气道结构改变情况;RT-PCR测定各组小鼠肺组织GPR43mRNA的表达变化;免疫组化观察肺中GPR43的表达及定位.结果 哮喘组BALF嗜酸性粒细胞(EOS)与对照组相比明显增高,地塞米松组明显低于哮喘组(P＜0.01);HE染色提示哮喘组气道上皮出现EOS等大量炎性细胞浸润,管壁厚度较对照组明显增加(P＜0.01);RT-PCR结果提示GPR43受体mRNA的表达量在哮喘组最低,与对照、地塞米松组相比有统计学差异(P＜0.01);免疫组化图像分析提示GPR43蛋白表达哮喘组明显降低,与对照组、地塞米松组相比均有显著性差异(P＜0.01).结论 哮喘小鼠肺组织中GPR43表达下降,地塞米松能部分上调其表达,从而减轻气道炎症反应.     

香烟提取物对支气管哮喘大鼠气道平滑肌细胞增殖的影响

目的： 探讨香烟提取物（CSE）对支气管哮喘(简称哮喘)大鼠气道平滑肌细胞（ASMCs）增殖作用及可能机制。方法: 16只SD大鼠随机分为对照组和哮喘组,各8只。原代培养大鼠ASMCs,取第3-6代细胞,分为对照组、对照+CSE组、哮喘组、哮喘+CSE组、哮喘+CSE+嘧啶基-苯磺酰胺（GW8510,细胞周期蛋白依赖激酶-4抑制剂）组、哮喘+GW8510组。用流式细胞术、四甲基偶氮唑盐（MTT）法及增殖细胞核抗原（PCNA）免疫细胞化学技术检测ASMCs增殖;用逆转录-聚合酶链反应（RT-PCR）和蛋白质印迹（Western blotting）检测细胞周期蛋白D1(cyclin D1)的表达。结果: （1）哮喘组ASMCs与对照组ASMCs相比,在S+G2/M期比例、吸光度（A）值和PCNA表达率上明显增高,差异显著（P＜0.01）。（2）哮喘组ASMCs S+G2/M期比例、吸光度（A）值和PCNA表达率分别为(18.30±1.12)%、0.512±0.110、(55.1±3.7)%;哮喘+CSE组分别为（32.12±1.17）%、0.801±0.210、（90.2±7.3）%;哮喘+CSE+GW8510组分别为(17.21±0.95)%、0.508±0.009、(54.3±4.8)%;哮喘+GW8510组分别为(11.16±1.48)%、0.345±0.078、(40.6±5.4)%。除哮喘组、哮喘+CSE+GW8510组两组比较差异无显著外,其余两两比较差异均显著（P＜0.01）。（3）哮喘组、哮喘+CSE组、哮喘+CSE+GW8510组、哮喘+GW8510组ASMCs cyclin D1 mRNA A值比值和蛋白表达A值比值分别为0.236±0.045、0.271±0.002;0.369±0.124、0.379±0.002;0.231±0.075、0.261±0.002;0.165±0.064、0.193±0.002。除哮喘组、哮喘+CSE+GW8510组两组比较差异无显著外,其余两两比较差异均显著（P＜0.01）。结论: 正常与哮喘大鼠ASMCs在CSE干预后增殖明显加快,cyclin D1表达明显增加。CSE可能是通过cyclin D1参与调控哮喘大鼠ASMCs的增殖。     

诱导痰处理温度对支气管哮喘诱导痰中气道炎性反应标志物浓度的影响

目的 探讨诱导痰处理温度对哮喘患者诱导痰中炎性细胞分类及其气道炎性反应标志物浓度的影响.方法 收集2013年3月至2013年8月在广州呼吸疾病研究所就诊的哮喘患者52例,所有受试者进行痰诱导,选取痰黏液加入4倍体积0.1％的二硫苏糖醇(DTT)后,分别于0℃冰浴与37℃水浴下孵育15 min(15 min冰浴组和15 min水浴组,n=28)和30 min(30 min冰浴组和30 min水浴组,n=10).细胞沉淀行HE染色后进行分类计数,同时采用悬浮芯片方法检测痰上清白细胞介素(IL)-5、IL-10、IL-17、干扰素(IFN)-γ和肿瘤坏死因子(TNF)-α.比较不同诱导痰处理温度对痰细胞计数及气道炎性反应指标水平的影响.结果 52例哮喘患者,痰诱导成功28例,成功率为53.8％.15 min冰浴组和15 min水浴组比较、30 min冰浴组和30 min水浴组比较,其痰液重量、痰细胞总数、细胞存活率和痰细胞分类差异均无统计学意义(均P＞0.05).15 min冰浴组和15 min水浴组痰上清IL-10、IL-17、IFN-γ、IL-5和TNF-α的浓度比较差异无统计学意义(均P＞0.05);30 min冰浴组和30 min水浴组痰上清IL-10、IL-17和IFN-γ的浓度差异无统计学意义(均P＞0.05),但30 min水浴组的IL-5和TNF-α浓度要高于30min冰浴组[IL-5:2.55 (2.20～4.35) ng/L比2.03(1.52～2.50) ng/L,TNF-α:19.41(9.07～37.92) ng/L比10.78(8.58～ 17.93)ng/L,均P＜0.05].结论 诱导痰处理温度会影响诱导痰中某些气道炎性反应标志物的浓度.在诱导痰处理时DTT裂解后,置于0℃冰浴下操作,可以较真实反映诱导痰中炎性反应标志物的真实浓度.     

哮喘大鼠外周血T淋巴细胞TH1/TH2细胞因子和PKCα的表达及银杏叶制剂对其影响

目的探讨银杏叶制剂对在哮喘免疫学发病机制中起关键作用的T淋巴细胞部分生物学功能的影响.方法 14只SD大鼠随机分成哮喘和正常两组,每组7只.从每只大鼠外周血分离出T淋巴细胞进行分组培养,72 h后用RT-PCR检测各组IL-2、IL-4、IL-5 mRNA的表达量,Westernblot检测各组细胞膜与细胞浆蛋白激酶Cα(protein kinase C α,PKCα)的表达比率.结果 IL-2、IL-4、IL-5mRNA表达量在哮喘组分别为0.58±0.086、1.03±0.12、0.48±0.08,正常组分别为0.45±0.03、0.35±0.08、0.15±0.05,各因子两组间比较差异有统计学意义(P＜0.01);哮喘组T淋巴细胞给予BN-52021干预后IL-2、IL-4、IL-5 mRNA的表达量明显下降(分别为0.49±0.05、0.55±0.09、0.27±0.05,P＜0.05);正常组IL-2/IL-4 mRNA的比值为1.27±0.20,哮喘组为0.60±0.18,两组比较差异有统计学意义(P＜0.01),其中哮喘组给予BN-52021干预后比值有所增大0.92±0.15,与未干预组比较有明显变化(P＜0.01).哮喘PMA+BN-52021干预组IL-2、IL-4、IL-5 mRNA表达量分别为1.52±0.25、1.99±0.36、0.68±0.21,明显低于哮喘PMA干预组(P＜0.05),而PMA+Ro31-8220组与PMA+Ro31-8220+BN-52021干预组比较差异无统计学意义(P＞0.05).哮喘空白组PKCα在T淋巴细胞胞膜与胞浆的表达量比率为0.629±0.093,显著高于正常对照组(0.056±0.012,P＜0.01),BN-52021干预后哮喘组比率较未干预组明显下降0.395±0.098(P＜0.05),PMA+BN-52021干预组PKCα比率为0.719±0.163,较PMA干预组(1.28±0.28)低(P＜0.05);哮喘各组T淋巴细胞胞膜与胞浆PKCα表达量的比率与IL-4 mRNA表达量的相关性分析(n=42,r=0.845,P＜0.01)显示呈明显正相关.结论银杏叶制剂对体外培养的哮喘大鼠T淋巴细胞因子IL-2、IL-4、IL-5的分泌均具有抑制作用,而对IL-2分泌的抑制作用相对较弱;银杏叶制剂对哮喘大鼠T淋巴细胞胞膜与胞浆PKCα的表达量比率具有明显的下调作用.     

哮喘模型大鼠肺组织一氧化氮合酶的分布

研究一氧化氮 (NO)在哮喘大鼠肺组织中的作用。采用组化法观察一氧化氮合酶 (NOS)在大鼠哮喘模型肺组织中的分布 ,应用免疫组化法观察大鼠哮喘模型气道mIL 2R+ 细胞变化。结果显示 ,哮喘大鼠肺NADPH染色呈强阳性 ,并波及肺泡膈。肺组织中NOS含量明显高于对照组 [哮喘组 (37 44± 0 77)pmol/mg,对照组 (8 73± 0 79)pmol/mg],气道炎性细胞增多 ,特别是mIL 2R+ 细胞 [哮喘组mIL 2R+ 细胞为 (2 3 8± 7 9)个 ,对照组为 0个 ],而NOS抑制剂DMA组气道炎性细胞少 ,NADPH呈阴性。提示NO是哮喘大鼠的炎性效应分子。     

哮喘豚鼠下呼吸道MMP-2的表达及NGF的调节作用

目的探讨基质金属蛋白酶-2(MMP-2)在哮喘豚鼠下呼吸道的表达及神经生长因子(NGF)对MMP-2的调节作用。方法应用免疫组织化学方法检测各组豚鼠下呼吸道MMP-2免疫反应的变化。用W estern b lot蛋白印迹方法检测各组豚鼠肺组织NGF和MMP-2的表达。用Luzex-F实时图像分析系统和凝胶成像分析系统分别对结果进行图像分析。结果①免疫组织化学结果显示:豚鼠气道上皮和肺内炎性细胞的MMP-2阳性免疫反应产物的平均灰度值(0-深色,255-浅色),生理盐水组(185.60±4.81、161.47±5.71)与单纯致敏组(184.80±9.64、160.33±4.03)比较没有显著差异(P>0.05);哮喘组(141.93±4.66、129.77±4.07)明显低于生理盐水组和单纯致敏组(P<0.01);哮喘+NGF抗体组(鼻腔吸入NGF抗体,179.73±6.11、150.23±8.13)则明显高于哮喘组(P<0.01)。②W estern b lot结果显示:与生理盐水组和单纯致敏组比较,哮喘组豚鼠肺组织MMP-2和NGF阳性产物的IDV(Integrated Density Value)与β-actin IDV的比值均明显升高(P<0.01),而哮喘+NGF抗体组则明显低于哮喘组(P<0.01),表明NGF可上调MMP-2的表达。结论MMP-2可能是哮喘气道重塑的一种调控因素,NGF诱发MMP-2的表达可能是NGF参与哮喘发病的机制之一,NGF抗体抑制哮喘时下呼吸道MMP-2的表达有可能延缓气道重塑的发生,可能是治疗哮喘的新途径。     

IL-13对小鼠哮喘模型气道黏蛋白基因Muc5ac及Bcl-2、Bax表达的作用

目的研究白细胞介素-13(IL-13)处理小鼠支气管哮喘(哮喘)模型前后肺组织黏蛋白基因Muc5ac、凋亡相关蛋白Bcl-2和Bax表达的作用,探讨气道黏液过度分泌的机制.方法45只雄性BALB/c小鼠随机分为对照组、哮喘组和IL-13组,每组15只.用逆转录-聚合酶链反应(RT-PCR)方法和免疫组化法分别检测Muc5acmRNA、Muc5ac蛋白、Bcl-2蛋白以及Bax蛋白在肺组织的表达.结果哮喘组和对照组肺组织Muc5acmRNA分别为(0.1552±0.0057)和(0.0633±0.0013),Muc5ac蛋白分别为(0.8849±0.0257)和(0.1166±0.0064),两组比较差异均有统计学意义(P<0.01);IL-13组肺组织Muc5acmRNA和蛋白分别为(0.2807±0.0027)和(1.6138±0.0483),与哮喘组、对照组比较差异也均有统计学意义(P均<0.01).与对照组Bcl-2蛋白(0.3279±0.0136)、Bax蛋白(1.7284±0.0263)相比,哮喘组分别增加和降低(分别为0.8383±0.0310和0.8987±0.0106),两组差异均有统计学意义(P均<0.01);IL-13处理后可分别促进Bcl-2和Bax蛋白增加和降低(分别为1.6934±0.0229和0.3522±0.0152),其和哮喘组的差异均有统计学意义(P均<0.01);哮喘组和IL-13组小鼠肺组织Muc5acmRNA、蛋白表达与Bcl-2蛋白表达均呈直线正相关(P均<0.05),而与Bax蛋白表达则均呈直线负相关(P均<0.05).结论IL-13是引起哮喘气道黏液过度分泌的重要细胞因子,它可能通过改变Bcl-2和Bax的表达导致了上述病变.     

钙调神经磷酸酶在哮喘豚鼠气道重塑中的作用

目的:观察钙调神经磷酸酶(CaN)在哮喘豚鼠气道重塑中的作用。方法:实验分3组:对照组、哮喘组及CaN抑制剂环孢霉素(CsA)组,测定指标包括:①支气管肺泡灌洗液(BALF)蛋白含量、细胞计数及分类;②大气道平滑肌[³H]-TdR掺入量;③肺组织切片中小气道壁厚度及气道平滑肌厚度;④气管和肺组织CaN活性。结果:①BALF:CsA组蛋白含量、细胞计数及嗜酸粒细胞分别较哮喘组少46%、51%及60%(P＜0.01);②大气道平滑肌[³H]-TdR掺入量:CsA组较哮喘组低22%(P＜0.05);③小气道壁厚度:CsA组较哮喘组少34%(P＜0.01);气道平滑肌厚度:CsA组较哮喘组少37%(P＜0.01);④肺组织CaN活性:CsA组较哮喘组低52%(P＜0.01);气管CaN活性:CsA组较哮喘组低44%(P＜0.01)。结论:CsA可减轻哮喘豚鼠气道重塑,推测CaN参与气道重塑过程。     

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 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.