HBV感染者HLA-Ⅰ类和HLA-Ⅱ类基因单倍型分析

目的 本研究对黑龙江地区乙型肝炎病毒(HBV)感染者进行了人类白细胞抗原(HLA)Ⅰ类和Ⅱ类基因单倍型分析,并结合HBV-C2亚型探讨其与HBV感染者最终清除病毒和慢性持续的关系.方法 本研究共230个HBV感染者与210个健康无血缘关系健康人作为对照进行比较,并对所有患者进行了HLA等位基因分型和单倍型的连锁分析.结果 本地区最常见的单倍型是A*02-B*40.A*02-DRB1*08,A*02-DRB1*09,A*02-DRB1*12,A术11-DRB1*15,A*24-DRB1*09,A*33-DRB1*07,B*13-DRB1*12,B*15-DRB1*15,B*40-DRB1*08,B*40-DRB1* 09,B*51-DRB1* 09,B*51-DRB1*15,和A*02-B* 15-DRB1* 09携带者可能更易于感染HBV,而A*24-B*13,B*13-DRB1*09,A*02-DRB1*07,A*33-DRB1*13,A*33-DRB1*15,和A* 02-B* 40-DRB1* 15可能保护机体免受HBV感染.另外A*02-DRB1* 12可能还与病毒持续慢性感染相关.感染HBV C2亚型病毒后,A*24-DRB1* 14,B*15-DRB1* 04,A*02-B* 15,A*02-DRB1* 15和A*02-B15-DRB1* 09携带者可能伴有急性的临床发作过程并最终清除病毒.结论 本研究报道了HLA单倍型与HBV感染亚型与感染者临床预后的关系,对HBV的潜在的靶向治疗提供了一定的理论基础.     

新疆地区汉族和维吾尔族部分人群HLA-DRB1、HLA-DQB1、HLA-DPB1基因多态性与单倍型的比较

目的了解中国新疆维吾尔自治区汉族和维吾尔族人类白细胞抗原DRB1(HLA-DRB1)、HLA-DQB1、HLA-DPB1高分辨分型基础上的基因多态性和单倍型分布的特点。方法应用聚合酶链反应-直接测序基因分型(PCR-SBT)法对新疆地区188例汉族人群与90例维吾尔族人群进行HLA-DRB1、HLA-DQB1、HLA-DPB1基因分型,直接计数法计算基因频率,应用Arlequin3.5软件以最大似然法获得单倍型频率。结果汉族人群频率最高的HLA-Ⅱ类基因分别是DRB1*09∶01(12.8%)、DQB1*03∶01(20.3%)和DPB1*05∶01(33.5%);三位点组成的单倍型频率最高的分别是DRB1*09∶01-DQB1*03∶03(8.8%)、DRB1*09∶01-DPB1*05∶01(5.0%)、DQB1*03∶01-DPB1*05∶01(9.6%)和DRB1*09∶01-DQB1*03∶03-DPB1*05∶01(6.3%)。维吾尔族人群频率最高的HLA-Ⅱ类基因分别是DRB1*07∶01(18.3%)、DQB1*03∶01(18.9%)和DPB1*04∶01(30.0%);三位点组成的单倍型频率最高的分别是DRB1*07∶01-DQB1*02∶02(16.1%)、DRB1*07∶01-DPB1*04∶01(5.0%)、DQB1*03∶01-DPB1*04∶01(7.3%)、DRB1*07∶01-DQB1*02∶02-DPB1*04∶01(7.4%)。两组人群中等位基因有显著差异的是∶DRB1*04∶04、DRB1*07∶01、DRB1*08∶03、DRB1*11∶04、DRB1*12∶02、DRB1*13∶01、DRB1*15∶01、DQB1*02∶02、DQB1*06∶01、DPB1*04∶01和DPB1*05∶01。结论中国新疆汉族与维吾尔族人群HLA-DRB1、HLA-DQB1、HLA-DPB1等位基因频率、单倍型频率分布均有自己的多态性特征。     

HLA-DRB1*12:01:01G和HLA-DRB1*14:01:01G组内等位基因频率的统计分析

目的 区分并计算人类白细胞抗原(human leukocyte antigen,HLA) HLA-DRB1* 12:01:01G(HLA-DRB1* 12:01:01/12:06/12:10/12:17)和HLA-DRB1* 14:01:01G(DRB1* 14:01:01/14:54)组内等位基因及其相对频率,并分析其与HLA-DRB3和HLA-DQB1的连锁情况.方法 收集115例HLA-DRB1*12:01:01G组和108例HLA-DRB1*14:01:01G组标本,采用单核苷酸序列分析(polymerase chain reaction-sequence based typing,PCR-SBT)方法检测HLA-DRB1* 12:01:01G组等位基因的第1～3外显子序列和HLA-DRB1* 14:01:01G组的第2、3外显子序列.HLA-DRB3和HLA-DQB1基因分型采用PCR-SBT方法.结果 115例HLA-DRB1* 12:01:01G组标本中,101例(87.8％)为HLA-DRB1* 12:01:01,14例(12.2％)为HLA-DRB1* 12:10,未发现HLA-DRB1* 12:06和HLA-DRB1* 12:17. 108例HLA-DRB1*14:01:01G组标本全部为HLA-DRB1*14:54. HLA-DRB1*12:01:01与HLA-DRB3* 01:01:02和HLA-DQB1* 03:01连锁,HLA-DRB1* 12:10则与HLA-DRB3* 02:02:01和HLA-DQB1* 03:01连锁.HLA-DRB1* 14:54与HLA-DRB3* 02:02:01和HLA-DQB1* 05:02、*05:03连锁.结论 HLA-DRB1* 12:01:01G组中HLA-DRB1* 12:01:01频率最高,而HLA-DRB1* 14:01:01G组则以HLA-DRB1* 14:54频率最高.     

昆明白族和彝族人群HLA-DRB1/DQB1等位基因遗传特点及频率分布比较

目的研究昆明白族和彝族儿童HLA-DRB1／DQB1等位基因多态性,分析比较昆明白族和彝族人群的遗传特点。方法采用PCR-SSP基因分型技术,分别对70名白族儿童和70名彝族儿童进行HLA-DRB1／DQB1基因分型。结果昆明白族儿童在HLA-DRB1位点上共检出13种等位基因,依次为DRB1*08(20．7％)、*04(16．4％)、*12(16．4％)、*15(8．57％)、*0901(8．57％)、*14 (6．43％)、*11(5．71％)、*16(5．00％)、*13(4．29％)、*07(2．86％)、*03(2．86％)、*01 (1．43％)、*10(0．71％);HLA-DQB1位点上共检出7种等位基因,依次为DQB1*0301(23．6％)、*06(21．4％)、*05(18．6％)、*04(18．6％)、*0303(7．14％)、*0302(6．43％)、*0201(4．29％)。彝族儿童在HLA-DRB1位点上共检出12种等位基因,依次为DRB1*12(33．57％)、*0901 (11．43％)、*04(11．43％)、*01(8．57％)、*11(7．86％)、*14(7．14％)、*15(7．14％)、*08 (5．00％)、*03(2．83％)、*13(2．14％)、*07(1．43％)、*16(1．43％);HIA-DQB1位点上共检出7种等位基因,依次为DQB1*0301(45％)、*05(22．14％)、*0303(12．14％)、*04(6．43％)、*06 (6．43％)、*0201(4．29％)、*0302(3．57％)。组间比较HLA-DRB1／DQB1等位基因总体分布及诸多等位基因频率均有显著差异。结论昆明白族和彝族人群HLA-DRB1／DQB1等位基因分布具有各自遗传特点。     

中国汉族人群供-受者HLA-A、B、Cw、DRB1和DQB1高分辨等位基因频率分布及错配比例的研究

目的 从基因高分辨水平,分析中国汉族人群供-受者人类白细胞抗原(human leukocyte antigens,HLA)-A、B、Cw、DRB1、DQB1各位点等位基因频率和分布的多态性;及供-受者等位基因匹配情况.方法 采用基因测序分型(sequence based typing,SBT)、序列特异性寡核苷酸探针法(sequence specific oligonueleotide probe,SSOP)和序列特异性引物法(sequence specific primer,SSP),对2540名中国汉族人的(其中1168名受者,1372名供者)DNA标本进行HLA高分辨基因分型,并作统计学处理.结果 2540份样本中共检测到44种HLA-A等位基因,频率高于0.05的A*1101、A*2402、A*0201、A*0207、A*3303、A*0206、A*3001共占80.4%;81种HLA-B等位基因,频率高于0.05的B*4001、B*4601、B*5801、B*1302、B*5101共占43.0%;44种HLA-Cw等位基因,频率高于0.05的Cw*0702、Cw*0102、Cw*0304、Cw*0801、Cw*0602、Cw*0303、Cw*0302、Cw*0401共占80.3%;61种HLA-DRB1等位基因,频率高于0.05的DRB1*0901、DRB1*1501、DRB1*1202、DRB1*0803、DRB1*0701、DRB1*0405、DRB1*0301、DRB1*1101共占70.1%;22种HLA-DQB1等位基因,频率高于0.05的DQB1*0301、DQB1*0303、DQB1*0601、DQB1*0602、DQB1*0202、DQB1*0302、DQB1*0401、DQB1*0502、DQB1*0201共占87.4%.这5个位点均处于杂合子缺失状态,其中A、B、DRB1位点符合HardyWeinberg平衡(Hardy-Weinberg equi1ibrium,HWE)(P＞0.05);Cw、DQB1位点偏离HWE(P＜0.05);排除个别基因型观察值与期望值偏差较大外,这5个位点均符合HWE.在供-受者数据的比较中,HLA全相合(10/10)的比例仅22.4%;单个等位基因错配(9/10)的比例为24.6%;两个等位基因错配(8/10)的比例为26.3%.结论 中国汉族人群高分辨水平HLA-A、B、Cw、DRB1,DQB1等位基因频率及分布特点,对非亲缘造血干细胞移植供者检索有重要参考价值;并为中华骨髓库数据入库和利用提供遗传学依据.

Abstract：

Objective To analyze the allele frequencies and polymorphism of human leukocyte antigens (HLA) -A, B, Cw, DRB1 and DQB1 between donors-recipients on high-resolution typing; and to analyze the matching and mismatching proportion between donors and recipients. Methods HLA highresolution types were determined by sequence based typing (SBT), sequence specific oligonucleotide probe (SSOP) and sequence specific primer (SSP) on 2540 unrelated Chinese Han individuals including 1168 recipients and 1372 donors, then statistical analyses were carried out. Results Forty-four HLA-A alleles were detected, and among them the frequencies of A * 1101, A * 2402, A * 0201, A * 0207, A * 3303, A *0206 and A * 3001 exceeded 0.05, and accounted for 80.4%. Eighty-one HLA-B alleles were detected, and frequencies of B * 4001, B * 4601, B * 5801, B * 1302 and B * 5101 exceeded 0. 05, and accounted for 43. 0% of total. There were 44 HLA- Cw alleles, among them the frequencies of Cw * 0702, Cw * 0102,Cw * 0304, Cw * 0801, Cw * 0602, Cw * 0303, Cw * 0302 and Cw * 0401 exceeded 0.05, and were 80.3 %of total. There were 61 HLA-DRB1 alleles, the frequencies of DRB1 * 0901, DRB1 * 1501, DRB1 * 1202,DRB1 * 0803, DRB1 * 0701, DRB1 * 0405, DRB1 * 0301 and DRB1 * 1101 exceeded 0. 05, and were 70. 1% of total. Finally, 22 HLA-DQB1 alleles were detected, the frequencies of DQB1 * 0301, DQB1 *0303, DQB1 * 0601, DQB1 * 0602, DQB1 * 0202, DQB1 * 0302, DQB1 * 0401, DQB1 * 0502 and DQB1 *0201 exceeded 0. 05, and they were 87.4% of total. All the five loci were of heterozygote deficiency. The HLA-A, B and DRB1 loci conformed to Hardy-Weinberg equilibrium (HWE) (P＞0. 05); but HLA-Cw and HLA-DQB1 loci did not (P＜0.05). Except several particular genotypes, all the five loci conformed to HWE. After comparing data between donors and recipients, only 22.4% of recipients found HLA matched donors (10/10); 24. 6% of recipients found single HLA allele mismatched donors (9/10); 26. 3% of recipients had two HLA alleles mismatched donors (8/10). Conclusion The characteristics of allele frequencies and polymorphism of HLA-A, B, Cw, DRB1 and DQB1 on high-resolution typing in Chinese Han population is valuable for donor searching in unrelated hematopoietic stem cell transplantation, and it provides genetic basis for donor registry and usage of donor resource for Chinese Marrow Donor Program.     

Grave 病与 HLA-DQA1 和 HLA-DQB1等位基因多态性的相关性分析

目的 探索Grave病(Graves'disease,GD)与HLA-DQA1和HLA-DQB1等位基因多态性之间关系.方法 选取就诊于我院的Grave病患者为研究对象.使用PCR-SBT方法对Grave病患者及正常对照组进行测序分析,使用SPSS 19.0统计软件进行分析GD患者组与对照组间差异性.结果 GD患者的HLA-DQAl* 01:01、*01:03、* 03:03、* 05:03的频率显著高于对照组,HLA-DQA1* 02:01、*05:05的基因频率明显低于正常对照组,P均＜0.05,差异具有统计学意义.HLA-DQB1* 04:01、*06:01的频率显著高于对照组,HLA-DQB1 * 02:02、*05:01的基因频率明显低于正常对照组,P均＜0.05,差异具有统计学意义.结论 HLA-DQAl* 01:01、* 01:03、* 03:03、* 05:03和 HLA-DQB1 * 04:01、* 06:01 可能为 GD的危险因素.HLA-DQA1* 02:01、*05:05和 HLA-DQB1 * 02:02、* 05:01 可能为 GD 的保护因素.     

人类白细胞Ⅱ类抗原DR、DQ基因型与妊娠期糖尿病的相关性研究

目的探讨人类白细胞II类抗原DR、DQ基因型与妊娠期糖尿病的相关性。方法对26例GDM孕妇及同期入院的42例正常健康孕妇,采用序列特异性引物聚合酶链反应技术(PCR-SSP)检测HLA-II类抗原DR和DQ的等位基因。结果研究中发现,DQA1*0101、DQA1*0201、DQB1*0609、DRB l*07-DQA1*0201-DQB1*0201基因频率在GDM中显著高于正常对照组,两组比较,统计学有差异(Ρ<0.05)。DQB1*0301基因频率在GDM中显著低于正常对照组,两组比较,有统计学差异(Ρ<0.05)。结论人类白细胞II类抗原DR、DQ基因型与GDM的易感性和保护性存在关联。DQA1*0101、DQA1*0201、DQB1*0609、DRB l*07-DQA1*0201-DQB1*0201基因是GDM的易感基因。DQB1*0301基因是GDM的保护基因。     

昆明彝族人群HLA-DRB1、DQB1基因多态性

目的　调查昆明彝族 HL A- DRB1、DQB1基因的多态性。方法　应用聚合酶链反应 -序列特异性引物基因分型技术 ,对昆明地区 70名彝族健康儿童进行了 HL A- DRB1、DQB1位点的基因分型。结果在 HL A- DRB1位点共检出了 12种等位基因 ,其中等位基因频率大于 10 %的依次为 HL A- DRB1* 12 (33.5 7% )、DRB1* 0 90 1(11.4 3% )、DRB1* 0 4 (11.4 3% ) ,等位基因频率大于 5 %而小于 10 %的依次为 DRB1* 0 1(8.5 7% )、DRB1* 11(7.86 % )、DRB1* 14 (7.14 % )、DRB1* 15 (7.14 % )、DRB1* 0 8(5 % ) ,等位基因频率小于 5 %依次为 HL A- DRB1* 0 3(2 .86 % )、DRB1* 13(2 .14 % )、DRB1* 0 7(1.4 3% )、DRB1* 16 (1.4 3% )。在 HL A- DQB1位点共检出了 7种等位基因 ,其中等位基因频率大于 10 %的依次为 HL A- DQB1*0 30 1(45 % )、DQB1* 0 5 (2 2 .14 % )、DQB1* 0 30 3(12 .14 % ) ,等位基因频率大于 5 %而小于 10 %的依次为DQB1* 0 4 (6 .4 3% )、DQB1* 0 6 (6 .4 3% ) ,等位基因频率小于 5 %的依次为 DQB1* 0 2 0 1(4.2 9% )、DQB1* 0 30 2 (3.5 7% )。结论　昆明彝族 HL A基因多态性分布不同于北方汉族人群 ,也不同于南方汉族人群 ,有其独特性。     

西藏门巴族人群HLA-A、B和DRB1基因座多态性

目的 分析西藏门巴族HLA-A、B和DRB1 3个基因座的遗传特征，并研究其民族起源。方法应用序列特异性寡核苷酸探针反向斑点杂交技术对西藏自治区门巴族居住区47名门巴族无关个体HLA-A、B和DRB1基因座进行分型。对门巴族和我国其他11个群体(民族)的HLA-DRB1基因频率采用Neighbor-Joining(NJ)方法进行聚类分析。结果 在西藏门巴族人群中HLA-A基因座共检出23个等位基因，其中HLA-A*1101，A*2402，A*02011，A*0206基因最常见；HLA-B基因座共检出39个等位基因，其中HLA-B*3802，B*4001，B*4002，B*51011基因最常见；HLA-DRB1基因座共检出33个等位基因，其中HLA-DRB1*12021，DRB1*0403，DRB1*0701，DRB1*1201基因最常见，频率最高的等位基因分别是HLA-A*1101(0．2128)，HLA-B*3802(0．1064)和HLA-DRB1*12021(0．0851)。结论 西藏门巴族人群HLA基因座具有高度遗传多态性，聚类分析门巴族与西藏藏族遗传关系较近。     

HLA-DRB1、DQB1基因与汉族人群寻常型天疱疮的相关性研究

目的　探讨 HL A- DRB1、DQB1位点基因在汉族人群寻常型天疱疮易感性中的作用。方法用序列特异性引物 -聚合酶链反应方法 ,对 6 1例寻常型天疱疮 (pemphigus vulgaris,PV)患者和 5 7名正常对照进行了 HL A- DRB1、DQB1等位基因的分型 ,并分析了 DRB1、DQB1基因在两组中的分布。结果　与正常对照组比较 ,PV组 DR4、DRB1* 14 (* 14 0 1、* 14 0 4、* 14 0 5 )基因频率明显增高 (Pc分别 <0 .0 5及P<0 .0 1) ,差异有显著性 ;PV组 DQB1* 0 5 0 3、DQB1* 0 30 2基因频率明显增高 (Pc均 <0 .0 5 ) ,差异有显著性。对 DR4阳性样本的组内基因亚型分型结果发现 ,PV组中 DRB1* 0 4 0 3、DRB1* 0 4 0 6频率显著增高(Pc<0 .0 5 ) ,差异有显著性。 PV患者组单倍型 HL A- DRB1* 0 4 ,DQB1* 0 30 2和 HL A- DRB1* 14 ,DQB1* 0 5 0 3频率明显增高 (P<0 .0 5 )。结论　HL A- DRB1* 0 4 ,DQB1* 0 30 2和 HL A- DRB1* 14 ,DQB1* 0 5 0 3可能是汉族人 PV推测的易感单倍型。     

Topical organization of the projections of neurons of the substantia nigra and the ventral field of the tegmentum of the midbrain to the head of the caudate nucleus of the cat

Neuroscience and Behavioral Physiology -     

Asymmetry of the internal connections of the striate cortex of the cat in the projection zone of the center of the field of vision

Studies were carried out on the organization of the internal connections of the striate cortex in cats in the projection zone of the center (0–5°) of the field of vision by microintophoretic application of horseradish peroxidase to electrophysiologically identified orientational columns. The area containing neurons showing retrograde labeling in most cases extended in the mediolateral direction. Labeled cells were located in the upper (II, III) and lower (V, VI) layers of the cortex, and the shapes and orientations of the areas containing labeled neurons in these layers coincided. Spatial asymmetry was detected in the distribution of labeled neurons relative to the orientational column studied. Labeled cells were located predominantly medial to the columns, regardless of the distance from the projection of the area centralis. Considering the visuotopical map of field 17, the asymmetry detected here provides evidence that neurons in orientational columns have more extensive connections with neurons of the peripheral part of the cortex. An asymmetrical distribution of “silent” zones around the receptive fields of neurons in orientational columns is suggested, and that these appear to receive influences from the periphery of the visual field. Laboratory of Visual Physiology and Laboratory of Central Nervous System Morphology, I. P. Pavlov Institute of Physiology, Russian Academy of Sciences, 6 Makarov Bank, 199034 St. Petersburg, Russia. Translated from Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 82, No. 12, pp. 23–29, December, 1996.     

Effects of the lesion of the postcommissural part of the septum on the behavior of the rat.

The effects of the lesion of the postcommissural part of the septum on behavior of the rat has been studied. Results may be summarized as follows. An increase in the exploratory behavior in the open field which decreases rapidly; a decrease in the number of defecations in this test and a decrease in time leaving a dark environment for exploration. In the shuttle box test, no facilitation of the acquisition, but a permanent and quite significant increase in the intertrial activity has been found. We conclude that the lesions tend to decrease the emotivity of the subjects. An interpretation on the basis of the species -- specific defensive reactions explains the transitory and permanent effects of the lesions on the spontaneous activity.     

Characteristics of the topographic interrelation of the head of the pancreas and the duodenum and pathology of the organs of the pancreatoduodenal area

Seventy pancreatoduodenal complexes of 55 patients with chronic pancreatitis and tumours of this zone and 15 patients died from other diseases are studies histotopographically . The pieces of the pancreatic head tissue in the medial wall of the duodenum were found in 12 cases of the first group and in 4 control cases. The pancreatic tissue consisted either of all elements of this organ or cystically dilated ducts and seemed to infiltrate different layers of the duodenum wall. Three variants of the pancreatic head structure are suggested on the basis of anatomo-topographical interrelationships of the pancreatic head and duodenum. In 12 out of 14 cases chronic pancreatitis and carcinoma of organs of this zone were combined with the variants of the pancreatic head structure, in 2 cases there was a true heterotopy . Pathogenetic significance of these variants for the development of chronic pancreatitis is discussed.     

Influence of the level of the transmembrane potential on the dynamics of the extinction of the amplitude of the synaptic reactions of the snail under voltage clamping conditions

The influence of the level of the transmembrane potential on the dynamics of the extinction of the amplitudes of summary excitatory postsynaptic currents arising in identified giant parietal neurons in response to rhythmic stimulation of the intestinal nerve was investigated in a preparation of the isolated CNS of the common snail in order to identify the possibility of the participation of the postsynaptic element in synaptic plasticity. It was demonstrated that, at a greater value of the transmembrane potential, the decrease in the amplitudes of the postsynaptic currents which have been induced by rhythmic stimulation takes place more rapidly. It was also demonstrated that at a higher frequency of stimulation of the nerve, the effect of the influence of the membrane potential level on the dynamics of the synaptic reactions is more prominent. The data obtained may be regarded as an argument in favor of the possibility of the participation of the post-synapse in plasticity. This study was partially supported by the Russian Basic Research Fund (project No. 94-04-12209). Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow. Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 45, No. 1, pp. 171–179, January–February, 1995.     

Effect of the conditions of adaptation of the optic analyzer to the function of the thermoreceptors of the human skin

Summary A discussion is presented of the effect produced by light stimulation applied to the optic analyzer alone on the function of the temperature analyzer. The cutaneous-temperature analyzer was kept on constant illumination and temperature. The light effects from the retinal photoreceptors on the cutaneous thermoceptor system led to reflex changes of the functional rate of the latter. Conditions of the optic analyzer of light adaptation caused reflex adjustment of cold receptors as to heating. Dark adaptation of the eyes changed the functional state of the cold receptors, corresponding to their adjustment to low temperatures.(Presented by Active Member AMN SSSR V. V. Parin) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 57, No. 3, pp. 3–6, March, 1964