氢氟酸烧伤中毒对兔外周血单个核细胞凋亡与胞内钙浓度的影响

目的: 研究氢氟酸烧伤中毒对兔外周血单个核细胞(PBMC)早期凋亡百分率和胞内游离钙浓度([Ca²⁺]_i)的影响。方法: 用流式细胞仪检测兔烧伤染毒前后外周血单个核细胞的Annexin V变化, 以观察其早期凋亡百分率。用Fluo-3/Am荧光探针观察烧伤染毒前后外周血单个核细胞内Ca²⁺平均荧光强度值的变化, 以观察细胞内[Ca²⁺]_i的变化。 结果: 12只烧伤中毒兔外周血单个核细胞早期凋亡百分率显著增加, 烧伤染毒前后比较P<0.01。而12只烧伤中毒兔中8只染毒后1 h外周血单个核细胞内[Ca²⁺]_i显著降低, 烧伤染毒前后比较P<0.05。其余4只却表现[Ca²⁺]_i染毒前后比较P>0.05。 结论: 本实验氢氟酸烧伤中毒使兔外周血单个核细胞早期凋亡百分率显著增加, 外周血单个核细胞内[Ca²⁺]_i却显著降低。提示氢氟酸烧伤中毒引导的细胞凋亡并非细胞内[Ca²⁺]_i增加所引发。     

小鼠腹腔巨噬细胞基态游离钙离子浓度的不均一性及其和细胞反应性的关系

目的:在单细胞水平上研究小鼠腹腔巨噬细胞(PM)基态游离钙离子浓度([Ca²⁺]_i)的不均一性及其和细胞反应性的关系。方法:用荧光指示剂Fura-2/AM结合荧光显微镜成像系统检测单个PM基态的及用激动剂刺激细胞后的[Ca²⁺]_i;同时结合NBT染色法定量检测单个PM产超氧阴离子(O₂^-)水平。结果:对7只正常小鼠共392个PM基态[Ca²⁺]_i的研究表明小鼠PM的基态[Ca²⁺]_i呈正态分布[(54±24)nmol/L,n=392],但波动范围较大(从10nmol/L到高于100nmol/L),以[Ca²⁺]_i在40-60nmol/L的细胞数量最多(约占50%)。用PMA、fMLP刺激后PM[Ca²⁺]_i升高,且受刺激后[Ca²⁺]_i升高的峰值和基态[Ca²⁺]_i之间呈正相关(PMA刺激组:r=052,P<0.01,n=58;fMLP刺激组:r=0.59,P<0.01,n=44。此两组实验均以不同的小鼠重复3次,其它两只小鼠的结果与上同。下面的表述方法同此)。另外小鼠PM的基态[Ca²⁺]_i与其受PMA刺激后产生O₂^-的量也呈显著正相关(r=0.42,P<0.01,n=43,重复4次)。结论:小鼠PM的基态[Ca²⁺]_i是不均一的,且基态[Ca²⁺]_i的高低和该细胞对致炎因子的反应性密切相关。     

噻庚啶和山莨菪碱拮抗TNFα诱导的内皮细胞[Ca2+]i增高

目的：研究噻庚啶（Cyp）和山莨菪碱（Ani）对肿瘤坏死因子（TNFα）诱导单个内皮细胞内Ca²⁺浓度（[Ca²⁺]_i）变化的影响，以探TNFα介导休克和Cyp、Ani的抗休克的机制。方法：人脐静脉内皮细胞株（ECV304）接种于35 mm含2 mL DMEM培养基的组织培养盘中培养。Fluo-3/AM负载细胞，激光扫描共聚焦显微技术（LSCM）测定单个内皮细胞[Ca²⁺]_i。结果：TNFα使单个内皮细胞[Ca²⁺]_i呈剂量依赖性升高，在60 s内达到峰值，然后下降并保持在基础水平之上。共聚焦扫描图像显示细胞核区[Ca²⁺]_i升高比胞浆区明显，下降比胞浆区慢。Cyp（3×10^-5 mol/L或6×10^-5 mol/L）、Ani（2×10^-5 mol/L或4×10^-5 mol/L）均能显著抑制由TNFα（1.2×10^-9 mol/L）诱导的单个内皮细胞[Ca²⁺]_i升高。结论：TNFα诱导内皮细胞[Ca²⁺]_i升高可能是TNFα介导休克的重要机制；Cyp和Ani抑制TNFα诱导的[Ca²⁺]_i升高可能是其抗休克作用的机制之一。     

钙离子在半边旗提取物6F的细胞毒及诱导HL-60细胞DNA片段化中的作用

目的:研究蕨类植物半边旗提取物6F对HL-60细胞内游离钙浓度([Ca²⁺]_i)及Bcl-2蛋白表达的影响, Ca²⁺与6F细胞毒作用及诱导细胞DNA片段化的关系。方法:用荧光探针Fura-2/AM标记细胞内游离Ca²⁺, 在荧光分光光度计上测[Ca²⁺]_i;流式细胞仪检测Bcl-2的表达;噻唑蓝(MTT)法测定细胞成活率;二苯胺法测DNA片段化形成率。结果:6F作用后, HL-60细胞内[Ca²⁺]_i显著升高, 呈明显的时间剂量效应关系;6F降低Bcl-2的表达;于培养基中加2mmol/LCa²⁺、或加1mmol/LEDTA络合细胞外钙, 或加4μmol/L钙通道A₂₃₁₈₇升高细胞内钙浓度, 均可增强6F的细胞毒作用, 但均不影响6F诱导细胞DNA片段化程度。加入250μmol/LZn²⁺可显著降低6F所致DNA片段化率, 并可增强6F的细胞毒作用。结论:化合物6F可显著升高HL-60细胞[Ca²⁺]_i, 推测与6F降低Bcl-2的表达有关;6F诱导HL-60细胞DNA片段化可能是通过Ca²⁺-非依赖性DNA酶的作用所致。     

红景天苷促进培养乳鼠心肌细胞肌质网钙离子的释放

目的: 观察红景天苷对乳鼠心肌细胞胞浆Ca²⁺浓度的影响并分析其可能的作用机制。方法: 应用荧光指示剂Fluo-3/AM负载培养大鼠乳鼠的心肌细胞,用激光共聚焦显微镜动态观察胞内游离钙荧光信号强度的变化,检测不同浓度红景天苷对培养心肌细胞胞内游离钙离子浓度([Ca²⁺]_i)的影响。结果: 红景天苷浓度为15 mg/L、30 mg/L和60 mg/L时,细胞内的平均[Ca²⁺]_i升高,峰值分别为574.08±4.65、591.86±3.64和618.66±4.27(均P<0.01);有剂量依赖性而无时间依赖性。用维拉帕米阻断细胞膜外钙内流时,红景天苷同样引起细胞内[Ca²⁺]_i升高,峰值由357.74±3.13、387.17±2.37和391.43±1.34分别上升到480.86±3.98、496.70±3.08和522.18±3.19(均P<0.01)。结论: 红景天苷能升高乳鼠心肌细胞中[Ca²⁺]_i,其机制可能与其促进肌浆网钙离子释放有关。     

丹参对抗缺氧/复氧引起的大鼠心室肌细胞收缩和细胞内钙的改变

目的:观察丹参在常氧和缺氧/复氧过程中对心肌细胞收缩和电刺激诱导的细胞内钙([Ca²⁺]_i)瞬态的影响。方法: 采用酶解分离成年大鼠心室肌细胞化学缺氧模型, 用视频跟踪计算机系统和细胞内双波长钙荧光系统分别观察心肌细胞收缩力学和[Ca²⁺]_i等指标。结果:丹参(1-9 g/L)处理后降低心肌细胞最大收缩和舒张速率、收缩幅度以及电刺激诱导的[Ca²⁺]_i幅度, 且呈剂量依赖性。缺氧后, 与对照相比细胞收缩力和钙瞬态幅度降低、舒张末细胞长度缩短、舒张末钙水平增高;复氧后细胞收缩力、钙瞬态幅度和舒张末钙水平有所回复, 但不能达对照水平。用3 g/L的丹参处理后, 缺氧/复氧引起的心肌细胞最大收缩和舒张速率、收缩幅度和电刺激诱导的[Ca^2＋]_i幅度高于单纯缺氧组, 舒张末[Ca²⁺]_i水平低于单纯缺氧组。结论:丹参可对抗缺氧/复氧引起的大鼠心室肌细胞收缩力降低和细胞内动态和静态钙的变化。     

单个巨噬细胞超氧阴离子水平的定量检测方法

目的：建立单个巨噬细胞超氧阴离子（O₂^-.）水平的定量检测方法,从而达到在单细胞内同时检测O₂^-.和细胞内游离钙离子浓度（[Ca²⁺]_i）的目的。方法：分离小鼠腹腔巨噬细胞，用NBT还原法显示细胞产生O₂^-.的水平，以细胞加入NBT前与染色后的透光强度之比来定量表示该细胞产生O₂^-.的量；以荧光探针Fura-2/AM负载细胞检测单细胞内[Ca²⁺]_i。结果：①分别用PMA、OZ刺激细胞并用NBT还原法染色后细胞内均有黑色沉淀，但前者分布均匀而后者所产生沉淀多偏于一侧，呈明显的局域性分布；②用NBT孵育10 min后，细胞透光强度没有明显变化（n=43, P>0.05），用NBT刺激细胞产生黑色沉淀后细胞透光强度明显降低（P<0.01, n=43）。③在不同的聚焦状态下，无细胞背景区的透光强度没有明显变化，而细胞区透光强度变化明显，但各个细胞透光强度的变化趋势是一致的；④PMA处理3批巨噬细胞并用NBT法染色得到3组R_OI值的分布情况提示用R_OI值定量是合理的但批间差异过大；⑤静息状态下的小鼠腹腔巨噬细胞[Ca²⁺]_i与细胞受PMA刺激后的R_OI呈显著正相关（n=43, r=0.42, P<0.01）。结论：用NBT还原法染色前后细胞透光强度比值可以代表该细胞产生O₂^-.的量，进而我们可以在单细胞内同时检测O₂^-.和[Ca²⁺]_i。     

阿魏酸钠拮抗氧化型脂蛋白(a)对人动脉平滑肌细胞的作用

目的:研究脂蛋白(a)氧化前后致人动脉平滑肌细胞(SMC)增殖及细胞内游离钙浓度([Ca²⁺]_i)的变化,观察阿魏酸钠(SF)对其的影响。方法:Lp(a)经体外Cu²⁺氧化法氧化,硫代巴比妥酸(TBARS)比色法检测氧化程度,培养的人动脉SMC中分别加入不同浓度SF,作用12h后再与天然和氧化型Lp(a)共同孵育,以MTT比色法、流式细胞仪检测细胞增殖状况,采用荧光探针Fura-2/AM检测细胞[Ca²⁺]_i。结果:氧化型Lp(a)促人动脉SMC增殖的同时亦明显增加了[Ca²⁺]_i水平,作用较天然Lp(a)明显,SF(40,80mg/L)可显著抑制氧化型Lp(a)所致的细胞增殖和[Ca²⁺]_i增加,并呈剂量效应关系,而对天然Lp(a)所致的细胞增殖和[Ca²⁺]_i增加无明显影响。结论:氧化型Lp(a)通过升高[Ca²⁺]_i而显著促动脉SMC增殖可能是其致动脉粥样硬化的机制之一,SF拮抗这种作用可能与其抗氧化能力有关。     

钾通道对大鼠肺动脉平滑肌细胞[Ca2+]i的调节

目的:探讨在常氧、低氧条件下钾通道对大鼠肺动脉平滑肌细胞(PASMCs)[Ca²⁺]_i的调节。方法:采用钙荧光探针(Fura-2/AM)负载培养的大鼠PASMCs,观察常氧、低氧培养后3种钾通道抑制剂(4AP,TEA、Glib)对PASMCs[Ca²⁺]_i的调节,同时用四唑盐(MTT)比色法比较4AP、TEA、Glib对大鼠PASMCs增殖的影响。结果:(1)常氧状态下,PASMCs[Ca²⁺]_i为(156.91±8.60)nmol/L,低氧时为(294.01±16.81)nmol/L(P＜0.01)。(2)常氧状态下,4AP可引起PASMCs[Ca²⁺]_i升高,达(280.52±23.21)nmol/L(P＜0.01),而TEA、Glib无此作用。(3)低氧时,4AP和TEA都可引起PASMCs[Ca²⁺]_i的升高,分别为(422.41±24.28)nmol/L、(380.84±11.02)nmol/L(P<0.01),Glib无作用。(4)MTT比色法中,常氧和低氧状态下4AP均引起吸光度(A)值升高,分别是0.582±0.062,0.873±0.043(P＜0.01)。TEA仅在低氧时A值升高(0.729±0.041,P＜0.05),而Glib无论常氧还是低氧均无影响。结论:无论常氧还是低氧条件下,电压依赖性钾通道(K_V)对PASMCs[Ca²⁺]_i及其增殖起主要作用。钙激活的钾通道(K_Ca)在常氧条件下对[Ca²⁺]_i不起调节作用,而在低氧下使[Ca²⁺]_i降低,反应性地调节PASMCs增殖。ATP敏感性钾通道(K_ATP)无论在常氧还是低氧情况下对[Ca²⁺]_i的调节不起作用。     

缺氧复氧对人心房肌细胞内钙离子浓度的影响

目的和方法:观察缺氧、复氧对人心房肌细胞内钙离子浓度的影响。急性分离人心房肌细胞,以Fluo-3作为Ca²⁺指示剂,用激光共聚焦显微镜观察细胞内Ca²⁺浓度变化。结果:人心房肌细胞在缺氧前[Ca²⁺]ⁱ为(117±48)nmol/L。在缺氧15 min时,[Ca²⁺]ⁱ即增加为(187±64)nmol/L(P<0.05,vs缺氧前)。缺氧30 min时[Ca²⁺]ⁱ为(417±139)nmol/L(P<0.01,vs缺氧前)。缺氧后复氧30 min[Ca²⁺]ⁱ为(786±238)nmol/L(P<0.01,vs缺氧前)。结论:人心房肌细胞在缺氧状态下胞内Ca²⁺浓度升高,而当其短期复氧时,胞Ca²⁺浓度继续增加。     

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.