金黄色葡萄球菌肠毒素B对豚鼠哮喘模型Th1/Th2细胞因子的影响

目的研究金黄色葡萄球菌肠毒素B(Staphylococcal Enterotoxin B,SEB)对豚鼠支气管哮喘(简称哮喘)模型气道炎症及Th1/Th2细胞因子的影响。方法27只豚鼠随机分为对照组,模型组,SEB组各9只,用卵白蛋白(OVA)建立哮喘模型。末次激发豚鼠24-48 h内处理,支气管肺泡灌洗,直接记数总白细胞和嗜酸性粒细胞,观察肺组织病理改变,分装冻存支气管肺泡灌洗液做细胞因子检测。结果SEB组豚鼠肺泡灌洗液中嗜酸性粒细胞数量为(2.6±0.64)×106,显著低于模型组的(13.0±1.8)×106(P<0.01);肺组织哮喘炎症反应也轻于模型组;SEB组肺泡灌洗液中Th1细胞因子IFNγ-浓度(126.41±5.17)pg/mL,高于模型组(86.52±5.10)pg/mL(P<0.05);而Th2细胞因子IL-4浓度(50.02±2.79)pg/mL低于模型组(78.30±3.88)pg/mL(P<0.05)。结论SEB能减少哮喘豚鼠支气管肺泡灌洗液中嗜酸性粒细胞数量,可以通过调节Th1/Th2细胞因子的比值来减轻气道哮喘炎症反应。     

删除嗜酸性粒细胞对支气管哮喘模型小鼠sPLA2-X的影响

目的:探讨支气管哮喘中的分泌型磷脂酶A2-X(sPLA2-X)与嗜酸性粒细胞的关联,为支气管哮喘的治疗提供新的思路与策略。方法:SPF级6～8周雌性BABL/c小鼠48只,分为4组,每组12只,分为健康对照组、哮喘对照组、哮喘/嗜酸性粒细胞删除组及哮喘/嗜酸性粒细胞删除同型对照组。构建小鼠支气管哮喘模型,除健康对照组小鼠于0、7、14 d腹腔注射生理盐水外,其余组小鼠每只分别于0、7、14 d腹腔注射50μg OVA与2 mg氢氧化铝凝胶(溶于200μL生理盐水)。随后根据分组于第21和26天分别进行嗜酸性粒细胞删除抗体(anti-CCR3)及同型对照的腹腔注射及吸入麻醉后的删除抗体滴鼻。于雾化结束后48 h内完成小鼠肺功能检测,每组小鼠一半行全肺灌洗、一半用于肺组织切片HE染色,全血用于检测血清IgE,肺泡灌洗液(BALF)上清液应用于检测细胞因子,肺泡灌洗液细胞用于细胞总数、细胞分类及流式分析。结果:(1)与哮喘对照组相比,哮喘/嗜酸性粒细胞删除组小鼠的气道、肺泡炎症反应显著减轻。(2)哮喘/嗜酸性粒细胞删除组(OVA/anti-CCR3)支气管肺泡灌洗液中嗜酸性粒细胞的百分比显著降低(P0.05)。(3)与哮喘对照组比较,哮喘/嗜酸性粒细胞删除组小鼠气道高反应显著降低(P0.05)。(4)与哮喘对照组相比,哮喘/嗜酸性粒细胞删除组小鼠BALF上清与血清中的sPLA2-X水平均显著降低(P0.05)。(5)与哮喘对照组对比,哮喘/嗜酸性粒细胞删除组小鼠BALF上清中的IL-4、IL-5和IL-13水平显著降低,血清中IgE的水平也显著降低(P0.05)。结论:支气管哮喘中嗜酸性粒细胞与sPLA2-X有重要的关联。     

地塞米松对哮喘豚鼠气道壁厚度的影响

目的:探讨哮喘时气道壁厚度变化及地塞米松对气道壁厚度的影响。方法:豚鼠30只,随机分为对照组、哮喘组和地塞米松干预组各10只。以腹腔注射10%卵蛋白和1%卵蛋白雾化吸入复制慢性哮喘模型。治疗组在每次激发前给予地塞米松干预。对右肺行支气管肺泡灌洗后分离固定,石蜡切片,行HE染色,用Luzex-F图像分析系统,测量小气道内周长和厚度,计算厚度百分比。结果:哮喘组支气管肺泡灌洗液的细胞总数多于对照组(P<0.05),哮喘组气道壁厚度%[(11.21±3.11)%]显著大于对照组[(5.82±1.29)%](P<0.05);地塞米松干预组的支气管肺泡灌洗液细胞总数、嗜酸性粒细胞%和气道壁厚度%均明显低于哮喘组,有显著差异(P<0.05)。结论:慢性哮喘时气道壁厚度增加,结构重建;早期地塞米松治疗可减轻厚度的增加。     

金黄色葡萄球菌肠毒素对小鼠慢性哮喘模型的抗炎作用

目的：用金黄色葡萄球菌肠毒素A（SEA）和肠毒素B（SEB）干预幼年小鼠,观察它们对小鼠慢性哮喘气道炎症的影响以及对气道内相关细胞因子水平的调节作用。方法：实验组中BALB/c小鼠在出生后1周开始腹腔注射0.1 mL SEA或SEB（浓度1 mg/L）,隔天注射,共7次。其它小组注射相同剂量生理盐水对照。BALB/c 小鼠出生后4周建立哮喘模型,实验组和模型组分别在0、7和14 d用卵白蛋白（OVA）腹腔注射致敏,在28 d开始隔天OVA雾化激发哮喘,共7次,末次激发后24-48 h内取支气管肺泡灌洗液（BALF）,进行嗜酸性粒细胞和总白细胞计数,其余BALF离心-70 ℃冻存检测细胞因子,固定肺组织做病理切片分析。结果:SEA组和SEB组小鼠肺组织炎症反应轻于模型组,BALF中嗜酸性粒细胞数量少于模型组 (P＜0.05);SEA、SEB组BALF中Th1细胞因子干扰素-γ（IFN-γ）高于模型组(P＜0.05);而Th2细胞因子白细胞介素-4（IL-4）、白细胞介素-5（IL-5）和嗜酸性粒细胞趋化因子（eotaxin）均低于模型组(P＜0.01)。结论:早期感染 SEA、SEB可以减少小鼠慢性哮喘支气管肺泡灌洗液中嗜酸性粒细胞的数量,可能通过调节Th1/Th2细胞因子比值减轻气道中的哮喘炎症反应。     

卵蛋白致敏哮喘豚鼠淋巴细胞白介素—2活性增强及其机制

建立了卵蛋白致敏的哮喘豚鼠动物模型，并对其淋巴细胞白介素－２诱生能力的白介素－２ｍＲＮＡ的表达进行观察。结果显示致敏哮喘豚鼠腹腔灌洗细胞的支气管肺泡灌洗细胞主要是酸性粒细胞和淋巴细胞，致敏哮喘豚鼠支气管肺泡灌洗液和腹腔灌洗液的淋巴细胞白介素－２分泌水平均明显高于生理盐水对照组支气管肺泡灌洗液和腹腔灌洗液的淋巴细胞白介素－２分泌水平。     

IL-31在哮喘小鼠中的动态表达及对肺泡上皮细胞表达CCL11和CCL22的影响

目的通过观察IL-31在OVA诱导小鼠哮喘模型中的动态表达及IL-31对肺泡上皮细胞表达趋化因子CCL11和CCL22的影响,探讨IL-31在哮喘气道炎症中的作用。方法常规OVA法建立小鼠哮喘模型,于末次激发后取肺组织HE染色及AB-PAS染色,收集支气管肺泡灌洗液(BALF)进行白细胞和嗜酸性粒细胞(EOS)计数,ELISA法检测血浆中IgE、IL-4、IFN-γ、IL-31水平,荧光定量PCR检测肺组织IL-31R mRNA表达水平,同时体外培养小鼠肺泡上皮细胞,用IL-31处理24 h后检测CCL11和CCL22 mRNA的表达水平。结果成功构建哮喘小鼠模型,哮喘小鼠BALF中白细胞总数、嗜酸性粒细胞百分比和血浆中IgE水平明显增多。哮喘小鼠肺组织病理切片见中性粒细胞、EOS浸润。哮喘小鼠血浆中Th2类细胞因子IL-4水平明显高于对照组,Th1类细胞因子IFN-γ明显低于对照组。哮喘小鼠血浆IL-31水平和肺组织IL-31R mRNA表达水平明显增高,第2周至第8周虽略有降低但仍明显高于对照组。IL-31作用小鼠肺泡上皮细胞24h后,趋化因子CCL11、CCL22mRNA表达增高。结论IL-31通过刺激趋化因子表达募集炎性细胞,促进气道炎症的发生发展。     

骨髓间充质干细胞培养上清液治疗支气管哮喘及对肺部炎症的影响

背景：医学界普遍认为支气管哮喘是一种与Th2相关的免疫反应疾病,目前尚缺乏理想的治疗方法。骨髓间充质干细胞作为一种成体干细胞,不仅具有增殖和多向分化能力,还具有低免疫原性和免疫调节能力。 目的：探讨骨髓间充质干细胞培养上清液对支气管哮喘小鼠肺部炎症的影响。 方法：将20只实验小鼠随机分为对照组和实验组,每组10只,在第0天及第14天小鼠腹腔注射卵清蛋白溶液致敏,并在第24-26天雾化吸入卵清蛋白溶液激发。实验组从第24天开始,在每次激发前2 h,腹腔注射制备好的骨髓间充质干细胞培养上清液2 mL,对照组腹腔注射生理盐水。末次激发后麻醉致小鼠安乐死亡,采取血清、肺泡灌洗液及肺脏组织进行研究。 结果与结论：①对照组小鼠肺组织结构发生异常,黏膜下层和肌层内能够看见大量嗜酸性粒细胞及单核细胞浸润,经骨髓间充质干细胞培养液治疗后,实验组小鼠肺部炎症较轻。②实验组白细胞总数、嗜酸性粒细胞数、嗜酸性粒细胞百分比显著低于对照组(P < 0.01)。③实验组肺泡灌洗液以及血清中白细胞介素17水平显著低于对照组(P < 0.05);肺泡灌洗液以及血清中白细胞介素4水平与对照组比较差异无显著性意义(P > 0.05)。上述结果提示支气管哮喘小鼠腹腔注入骨髓间充质干细胞培养上清液能够减轻肺部炎性病理反应严重程度,降低肺泡灌洗液以及血清中相关的炎症指标水平。  中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程      

地塞米松对哮喘大鼠嗜酸性粒细胞中p53表达的影响

目的： 研究支气管哮喘支气管肺泡灌洗液（BALF）嗜酸性粒细胞中凋亡相关基因p53的表达以及地塞米松对其的作用及其机制。方法： 将36只大鼠随机分为对照组、哮喘组和激素组，并对其BALF的嗜酸性粒细胞进行计数，以免疫印迹法(Western blotting)检测嗜酸性粒细胞中p53的表达。结果： 哮喘组BALF的 总细胞数及嗜酸性粒细胞均高于激素组及对照组（P<0.01）。哮喘组BALF的嗜酸性粒细胞中p53表达弱于激素组和对照组（P<0.01）。结论： 哮喘气道炎症与嗜酸性粒细胞生存增加亦即嗜酸细胞凋亡减少密切相关。糖皮质激素可诱导嗜酸性粒细胞凋亡，其机制可能与促嗜酸性粒细胞凋亡的p53表达有关。     

雷公藤甲素对中性粒细胞性哮喘小鼠肺泡灌洗液中WBC和EOS的影响

目的:初步探讨雷公藤甲素对中性粒细胞哮喘小鼠肺泡灌洗液中WBC和EOS的影响。方法:采用卵清蛋白(OVA)联合脂多糖(LPS)致敏方法建立支气管哮喘小鼠模型,BALB/c小鼠32只随机分为中性粒细胞性哮喘组(NA组)、中性粒细胞性雷公藤甲素干预组(TLN组)、中性粒细胞性地塞米松干预组(DXN组)和正常对照组(NC组)各8只,血球计数板计算各组小鼠肺泡灌洗液(BALF)中WBC及EOS的总数目;涂片瑞士染色查看炎症细胞浸润情况。结果:DXN组、TLN组小鼠BALF中WBC总数、EOS总数及其浸润情况均较NA组明显下降(均P0.05),但均明显高于NC组(均P0.05),DXN组上述各指标均较TLN组明显升高(均P0.05)。结论:雷公藤甲素可减少BALF中WBC及EOS总数,抑制肺部WBC、EOS浸润,缓解中性粒细胞性哮喘气道炎症。     

磷脂酰肌醇3激酶对哮喘大鼠气道上皮细胞诱导型一氧化氮合酶表达的调控作用

目的： 探讨磷脂酰肌醇3激酶（PI3K）抑制剂wortmannin对哮喘大鼠支气管上皮细胞诱导型一氧化氮合酶（iNOS）表达的影响。方法: 24只成年哮喘大鼠随机分成对照组、哮喘组以及PI3K抑制剂wortmannin干预组。对支气管肺泡灌洗液（BALF）细胞总数及嗜酸性粒细胞进行计数,免疫组织化学检测大鼠支气管上皮细胞iNOS蛋白的表达,RT-PCR检测肺组织iNOS mRNA的表达,分光光度计检测肺组织PI3K活性、iNOS活性及NO含量。结果: 哮喘组大鼠BALF细胞总数计数及嗜酸性粒细胞分类均高于对照组;PI3K抑制剂wortmannin干预组BALF嗜酸性粒细胞计数及分类明显低于哮喘组,差异显著。哮喘组肺组织PI3K活性、iNOS活性及NO含量高于对照组,PI3K抑制剂wortmannin干预组肺组织PI3K活性、iNOS活性及NO含量低于哮喘组。哮喘组大鼠支气管上皮细胞iNOS蛋白及肺组织iNOS mRNA表达较对照组明显增强,但PI3K抑制剂wortmannin组iNOS蛋白及mRNA表达均明显弱于哮喘组。结论: PI3K可调节哮喘大鼠气道iNOS表达,影响哮喘气道炎症反应。     

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.