GENETIC VARIATION IN THE SHEEP RED BLOOD CELL

1. There are 7 well-established red-cell antigen (blood group) loci. The R-O system has 3 phenotypes, R, O and i, identified by the ‘naturally occurring’ antibodies, anti-R and anti-O. The R and O substances are also present in soluble form in some body secretions. The expression of R and O is controlled by a dominant gene I, epistatic in effect, at an independent locus from that of R. The systems, A, C, M-L, B, D and X-2 are identified by means of ‘immune-type’ antibodies, and several of the loci have multiple alleles. An isoenzymic form of serum alkaline phosphatase is associated with the R-O system. The frequency for the genes at the various loci has been determined in a limited number of breeds. 2. Some sheep red cells have high K+ and low Na+ concentrations (HK type, or Key), others have low K+ and high Na⁺ concentrations (LK type or Kea). Two other rare forms exist; Key type which is HK but with lower than normal K+ values, and Kep type which has approximately equal Na⁺ and K⁺ concentrations. The red cells of foetuses and newborn lambs have high K+ levels irrespective of their potassium genotype. HK cells have 3–4 times greater (Na+-K+)-activated ATPase activity, a 3–4 times increased rate of active K+ transport and a larger number of ouabain-binding sites than LK cells. Antigen M is present on homozygous HK and heterozygous LK red cells, and antigen L is present on homozygous and heterozygous LK red cells. Sensitization of LK cells with anti-L stimulates active K+ transport and ATPase activity and exposes a larger number of ouabain-binding sites in these cells. Anti-M has no effect. The red cells of newborn lambs only show weak L and M antigen activity. It is postulated that L antigen inhibits cation transport in LK cells by masking the pump sites on the membrane. Immature red cells in LK-type sheep have a high rate of active K+ transport and yet have L antigen present. No satisfactory explanation for this has yet been advanced. There is no conclusive evidence that the potassium types have any significance from the point of view of adaptation or sheep breeding. The potassium-gene frequencies are known for a large number of breeds. 3. Two allelic genes, Hb⁴ and Hb^B control 3 haemoglobin phenotypes, A, AB, and B. Foetal haemoglobin (HbF) is present in foetuses and newborn lambs. Sheep with HbA also synthesize small amounts of another haemoglobin (HbC) and under conditions of severe anaemia, synthesis of HbC takes over from that of HbA. No change in HbB is observed in anaemia. A rare haemoglobin (HbD) has been found in 3 Yugoslavian sheep. Hbs A, B, C and F differ in their physicochemical properties; they share the same alpha chains but their non-alpha chains differ in a number of amino acids. HbD differs from HbA in one amino acid in the alpha chain. Certain genetic aspects are discussed. There is some evidence that sheep with HbA are less fertile than those with HbB. The gene frequencies for Hb are known for a large number of breeds. 4. Two isoenzymic forms of carbonic anhydrase are found in red-cell lysates and these are controlled by a pair of allelic autosomal genes, producing 3 phenotypes, CAF, CAFS and CAS. Only a few breeds have been studied but CA^F is apparently quite rare. 5. An unidentified protein, designated ‘X’ is present in electrophoretic separations of haemolysates from some sheep. Its presence is dominant to its absence. Polymorphism at this locus is present in all breeds so far studied. 6. A deficiency of reduced glutathione (GSH) in red cells is found in some sheep and is inherited as an autosomal recessive disorder. Sheep with this deficiency have lower red-cell K+ and Na^f concentrations than normal and it is suggested that the HK GSH-deficient sheep may be Ked type sheep. This deficiency has so far only been found with certainty in one breed of sheep. 7. In sheep twin chimeras, admixture of red-cell antigens, haemoglobin and ‘X’ protein types has been found. Various aspects of chimerism, which occurs only rarely in sheep, are discussed. 8. The significance of the genetic variation is discussed in the light of the physiology and immunology of the red cell and of the sheep itself.     

客家人的红细胞血型分布

对父母双方上溯三代均为客家人的广东梅县200名 (其中男89人,女111人) 健康学生进行了红细胞血型ABO,MNSs,Rh,Kidd,Duffy,Diego,Xg,Lewis及P等系统的分布调查。结果显示,客家人的基因频率S=0.0250,NS=0,pl=0.0917和Fyb=0.0300,都是汉族人群中最低的。其它基因频率为r=0.6632,p=0.1863,q=0.1505;m=0.5250,n=0.4750,MS=0.0250,Ms=0.5000,Ns=0.4750,s=0.9750;C=0.6575,D=1.0000,E=0.1515,CDe=0.6226,cDE=0.1200,cDe=0.2189,CDE=0.0389;JKa=0.4642,JKb=0.4881,JK=0.0477;Fya=0.9700;Dia=0.0202,Dib=0.9798;Xga=0.3633,Xg=0.6367;P2=0.9083。发现了国内第二例Jk(a-b-)表型,未发现MNS型,NS型,NSs型,CCDEE型,CcDEE型,Fy(a-)型和Rho(-)型。Le(a+b-)型29人,Le(a+b+)型2人,Le(a-b+)型67人,Le(a-b-)型102人。客家人与国内19个群体的遗传距离计算结果表明,与客家人遗传距离最近的是福建汉族、湖南苗族、贵州汉族及广西侗族,其次为河南汉族、黑龙江汉族、陕西汉族,福建畲族及上海汉族,而与云南白族、辽宁满族、甘肃汉族、广西瑶族、广西壮族、内蒙汉族及四川彝族的遗传距离较远。与客家人遗传距离最远的是湖南土家族、海南苗族及海南黎族。     

青海高原6－7岁小儿红细胞形态定量分析

应用计算机辅助形态测量系统,对我国青海高原贵南县（海拔３１００ｍ）、玛多县（海拔４３００ｍ）６－７岁小儿红细胞形态进行了定量分析。与北京市儿童（平原地区）相比,高原正常儿童细胞平均周长、面积、直径较平原对照组大,而红细胞平均厚度减小（Ｐ＜０．０１）。且红细胞平均周长、面积、直径与海拔高度呈正相关。红细胞平均厚度与海拔高度呈负相关（Ｐ＜０．０００１）。在高原低氧状态下,红细胞形态的这种改变使红细胞比表面代偿性增加,这将更利于红细胞与周围的气体交换。红细胞形态的这种适应性改变具有重要的生理学意义。     

云南阿昌族的红细胞血型分布

调查了１０２名云南阿昌族的ＡＢＯ,ＮＮＳｓ,Ｒｈ和Ｐ系统的红细胞血型,结果表明,阿昌族的基因频率ｐ（０．３８７４）是迄今国内调查过人群中的最高值,Ｅ（０．２４５９）和ＣＤｅ（０．６９３６）基因或染色体频率较高,而Ｓ（０．０６８６）和Ｐ１（０．１０８９）频率较低;Ｍｓ（０．５９５０）连锁率高于Ｎｓ（０．３３５３）;未发现ＳＳ和Ｒｈ（－Ｄ）阴性表现型。     

宁夏回族红细胞血型的研究

调查了219名宁夏回族的 ABO、MNSs、Rhesus、P、Lewis、Duffr、Kidd Diego 、Kell、Lutheran和Xg等11种系统的红细胞血型。结果表明,宁夏回族有较高的q(0.2530)、Fy~a(0.9270)、CDe(0.6225) 和E(0.2660) 等基因或染色体频率;d(0.0557)、s(0.0594)、P_1(0.1316)和 Le~a(0.3882)等基因频率较低;而未发现K和Lu~a基因;Di~a的频率为0.0349,也处于低水平;Ns(0.4984)连锁率高于 Ms(0.4422);Xg~a基因频率为0.4432。11个系统的红细胞血型的分布和遗传距离分析均反映了宁夏回族的遗传组成具有我国北方民族的特征,尤其接近于北方汉族和蒙古族,与新疆维吾尔族则存在较大的差异。     

24种红细胞血型抗原在黑龙江省赫哲族人群中的分布

对３代均为赫哲族的黑龙江省同江县街津口乡和八叉乡的９４人进行了１０个红细胞血型系统（ＡＢＯ、Ｒｈ、ＭＮＳｓ、Ｄｕｆｆｙ、Ｋｉｄｄ、Ｌｕｔｈｅｒａｎ、Ｄｉｅｇｏ、Ｐ、Ｋｅｌｌ、Ｌｅｗｉｓ）共２３种抗原分布的调查,结果显示,基因频率ｑ（０．２２２３）〉ｐ（０．１６９２）,ｍ（０．６０１１）〉ｎ（０．３９８９）,为我国北方人群特点。其它基因频率为,ｒ＝０．６０８５;Ｓ＝０．０６９１,ｓ＝０．９３０９,Ｍ     

QUANTITATION OF HUMAN RED BLOOD CELL FIXATION BY GLUTARALDEHYDE

The uptake of glutaraldehyde by human red blood cells has been measured as a function of time by a freezing point osmometer. The rate of attachment of glutaraldehyde to the cell proteins is high over the first hour, declining to zero over a period of a few days. The number of glutaraldehyde molecules cross-linking with each hemoglobin molecule is of the order of 200, in reasonable agreement with the calculated number of attachment sites. The cell membrane is immediately highly permeable to glutaraldehyde. Selective permeability to ions is lost during fixation. Ionic equilibrium is obtained only after a few hours. An optimum fixation technique for shape preservation is suggested.     

中国不同人群的红细胞抗原多态性及血型组合

计算了汉、回、蒙古、维吾尔、侗、高山、朝鲜和壮等八个民族红细胞抗原常见等位基因数、常见血型和血型组合频率、血型相同的二人随机相遇的概率、血型组合数、常见和罕见的血型组合、AB、Rh(D-)型频率及排除亲子关系的概率。结果表明,中国北方民族的血型系统的多态程度比南方民族高。     

急性低氧对大鼠血粘度,红细胞变形能力和左心室功能的影响

健康ＳＤ雄性大鼠,体重２５０—３００ｇ,麻醉、气管插管,用人工呼吸机经气袋供气,自发吸入氧浓度为９％的氧氮混合气,用ＳＭＵＰ－ＰＣ生物信号处理系统处理左心室功能。结果：（１）急性低氧经动脉血气分析可见ＰａＯ２下降（Ｐ＜０．０１）,ｐＨ值升高（Ｐ＜０．０５）,ＰａＣＯ２稍下降（Ｐ＞０．０５）,左心室功能各指标如ＬＶＰ,ＨＲ,Ｖｍｐ,±ｄｐ／ｄｔｍａｘ,Ｖｃｅ４０,Ｖｍａｘ,Ｌ０、等均下降;血液流变学指标如全血粘度（高、低切值及其还原值）升高,红细胞滤过指数（ＩＦ）升高;复氧后上述各指标恢复正常。（２）静脉注射心得安（０．５ｍｇ／Ｋｇ）后,使急性低氧诱发的左心室功能各指标更加明显下降,而血液流变学各值不再明显上升;静脉注射酚妥拉明（３ｍｇ／Ｋｇ）后,使急性低氧诱发的血液流变学各值上升不明显。（３）石炭酸破坏双侧颈动脉窦区后也可致低氧诱发的左心室功能各指标进一步下降,而血液流变学指标也不再明显上升。结果提示：急性低氧可引起左心室功能下降和全血粘度升高,红细胞变形能力降低,复氧后可恢复;交感神经活动及颈动脉窦区化学感受性反射可能对抗低氧诱发的左心室功能的下降,促进血粘度的升高。     

高血压病红／白细胞变形性的研究

本文观察了52例原发性高血压和24例正常人的红细胞、白细胞变形性,红细胞膜钙泵、钠泵活性,血粘度及血浆粘度,结果发现:原发性高血压组高、中切变率血粘度和钠泵活性显著高于正常组,红细胞变形性和钙泵活性显著高于正常组;红细胞变形性和钙泵活性显著低于正常组.白细胞变形性、低切变率血粘度及血浆粘度与正常组比较无显著差别.原发性高血压组红细胞变形性与年龄、平均动脉压、钙泵活性,高、中切变率血粘度相关.心痛定和川芎嗪治疗后,红细胞变形性显著改善,川芎嗪还能降低高切变率血粘度.结果提示:在高血压病中红细胞变形性降低、血粘度增高的分子水平机制主要是红细胞膜钙泵活性降低。基于微循环的改善,在扩大治疗例数后,心痛定和川芎嗪可能作为降压治疗的优选药与辅助药。     

汞化合物对红细胞膜作用的研究

本文研究了汞化合物对红细胞膜作用的光谱变化,观察了膜蛋白的荧光和磷光,膜上DPH的荧光偏振和ANS与红细胞膜的结合,以及他们与汞产生红血球溶血的关系。 在5P7.5缓冲液中红细胞膜蛋白的荧光随HgCl_2 Hg(AC)_2和PCMB的浓度加大而降低,表现为快和慢双相变化的过程,其淬灭作用的大小为HgCl_2>Hg(AC)_2PCMB,这是由于膜上形成了不发荧光的R—Trp—Hg~ 络合物以及能量从Trp转移到R—S—Hg~ 络合物上。HgCl_2对膜蛋白磷光的作用也是随汞离子浓度加大而降低,但磷光/荧光比则是增加的。标记红细胞膜的DPH偏振度是随HgCl_2浓度增加,表明膜流动性是随汞离子浓度加大而降低。标记膜上的ANS的荧光强度随HgCl_2和Hg(AC)_2的浓度加大而增加,这是由于ANS与膜的结合数随汞离子浓度加大而增加的缘故。上述各种变化是与汞离子对红血球溶血的作用一致的。     

高三尖杉酯碱对兔红细胞膜钙调蛋白的抑制作用

本实验显示高三尖杉酯碱能在>5μg/ml浓度以上抑制兔红细胞膜上钙调蛋白活性(P<0.05).推测高三尖杉酯碱能通过影响癌细胞钙调蛋白活性干扰细胞钙代谢和减少阿霉素和长春新碱的抗药性.     

基诺族、布朗族和拉祜族的4种红细胞血型分布

调查了云南基诺族、布朗族和拉祜族各100人的 ABO、Rh、MN和 P血型系统。结果表明 ,ABO血型系统中 p基因频率拉祜族最高 (0 .2420 ) ,基诺族最低 (0 .0779) ,布朗族居中(0 .2144 )。 r基因频率是基诺族最高 (0 .6971) ,拉祜族最低 (0 .5288) ,布朗族居中 (0 .5964)。Rh血型系统中 ,基诺族和拉祜族都是以 CCDee和 Cc DE-为常见类型 ,而且都是 CCDee最高 ,Cc DE-次之。拉祜族和基诺族的 CDe频率分别为 0 .7433和 0 .6950 ;c DE频率分别为 0 .1 871和0 .2517;基因频率 d为零。MN血型系统中 ,这 3个民族都是基因频率 m>n。P血型系统中 ,本次调查的 3个民族的p1基因频率在全国已调查过的汉族和少数民族中均是最高值 (拉祜族0 .50 99,布朗族 0 .4690 ,基诺族 0 .4359)。     

ALTERATION OF THE CONFORMATION OF PROTEINS IN RED BLOOD CELL MEMBRANES AND IN SOLUTION BY FIXATIVES USED IN ELECTRON MICROSCOPY

The effects of several commonly employed fixatives on the three-dimensional conformations of two soluble proteins and the protein of intact red blood cell membranes have been studied by means of circular dichroism measurements in the spectral region of the peptide absorption bands. The fixatives used produced significant and parallel conformational changes in all of the proteins, in the increasing order: glutaraldehyde; OsO₄; glutaraldehyde followed by OsO₄; and KMnO₄. The last two treatments obliterated most of the helical character of the proteins. The significance of these observations to the preparation of specimens for electron microscopy is discussed.     

THE EFFECTS OF RED BLOOD CELL EXTRACTS ON THE PROLIFERATION OF ERYTHROCYTE PRECURSOR CELLS, IN VIVO

Saline incubation extracts of mature erythrocytes were assayed in vivo by a variety of techniques in order to study their ability to modify the proliferation of maturing erythroid cells. Using comparable extracts from granulocytes and lymphocytes, the specificity of the effect of the red cell extract for erythroid cells was confirmed by measurement of autoradiographic labelling indices, radio-iron incorporation and spleen colony growth. The erythroid cells were found to be very sensitive to the effects of the extract, as little as 10 μg per mouse producing a maximum effect on iron incorporation. It was found that the extract does not block erythroid cell proliferation completely but simply lengthens the cell cycle, mainly by increasing the G₁ phase of the cycle. There was no effect on the committed erythroid precursor cells. The in vivo activity, specificity and non-toxicity to the cells, together with the cells' sensitivity to red cell extract suggest, therefore, that this inhibitor may play a physiological role in the control of red cell production.