DNA typing of the HLA-A gene: population study and identification of four new alleles in Japanese

With the use of polymerase chain reaction (PCR) and sequence-specific oligonucleotide probe (SSOP), we established a DNA typing method of the HLA - A locus. A pair of primers to amplify the highly polymorphic region of HLA-A gene including exon 2 and exon 3 was designed and the amplified DNAs were hybridized with 91 types of ³²P labeled SSOPs. This method allowed discrimination of all known HLA-A alleles except for two combinations, A*0201 or A*0209 and A*0207 or A*0215N, which have identical sequences in exon 2 and exon 3. Another pair of primers was designed for amplification of exon 4 and the PCR products were hybridized with 5 SSOPs to distinguish A*0201 and A*0207 from A*0209 and A*0215N, respectively. In this study, 81 B-lymphoblastoid cell lines (BLCL) homozygous for HLA and 553 unrelated healthy Japanese individuals were determined for their HLA-A genotypes. Based on the genotyping results, frequency of HLA-A alleles and linkage disequilibrium between HLA-A and HLA-B in the Japanese population were investigated. In addition, four new HLA-A alleles were identified and their nucleotide sequences in exon 2 and exon 3 were determined to confirm the typing results.     

HLA-B*07 allele frequencies and haplotypic associations in Koreans

We have investigated the frequencies of HLA-B*07 alleles and their haplotypic associations with HLA-A, -C and -DRB1 loci in 489 healthy unrelated Koreans, including 214 parents from 107 families. All of the 45 samples (9.2%) typed as B7 by serology were analyzed for B*07 alleles using polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) method. Two different B*07 alleles were detected: B*0702 (allele frequency 0.041) and B*0705 (0.005). Two characteristic haplotypes showing strong linkage disequilibrium in Koreans were A*2402-Cw*07-B*0702-DRB1*0101 (haplotype frequency 0.028) and A*2901-B*0705-DRB1*0803 (0.005). The characteristic haplotype A*2901-B*0705-DRB1*0803, found in 100% (5/5) of B*0705-positive individuals, has not been previously described in other ethnic groups. HLA-B7 alleles comprise distinctive extended haplotypes in the Korean population. The probability of HLA-B7 allele mismatches among ABDR-matched unrelated donor-recipient pairs is expected to be low in Koreans.     

PON1Q192R基因多态性与冠心病患者使用氯吡格雷疗效的关系

目的：探讨不同民族PON1Q192R等位基因变异频率以及PON1Q192R基因多态性与冠心病患者氯吡格雷抵抗（CR）的关联性。方法：纳入新疆医科大学第二附属医院2020年1月至2020年12月使用氯吡格雷且诊断为冠心病的患者127例,患者每日服用氯吡格雷75 mg,5 d后用血栓弹力图测定相关参数,并进行CYP2C19*2、CYP2C19*3、CYP2C19*17和PON1Q192R基因分型检测。结果：不同民族之间PON1Q192R基因突变频率差异具有统计学意义（P <0.05）,患者的血栓弹力图参数结果显示,PON1Q192R基突变并不会显著降低氯吡格雷疗效。结论：PON1Q192R基因突变频率与冠心病患者氯吡格雷反应的相关性还需要进一步研究。     

切线时间常数在慢性阻塞性肺疾病及肺心病患者F-V曲线形状转变中的变化及临床意义

目的　探讨切线时间常数 ( τt)在慢性阻塞性肺疾病 ( COPD,慢阻肺 )和肺心病患者 F- V曲线形状转变中的变化及临床意义。方法　测定了 90例缓解期 COPD患者 (慢支 43例 ,肺气肿 47例 )及 31例合并肺心病患者的 F- V曲线。并在 F- V曲线上测量高、中、低肺容积的切线时间常数 τt75 、τt5 0 、τt2 5 ,与正常人和吸烟者的 τt作对比分析。结果　 1正常范围内 F- V曲线形状呈平台型、直线型、凸型和凹型 4种 ,| τt75 | >1s或 <1s,τt2 5 <1s,τt关系呈“青少年式”或“老年式”;2轻、中度异常的 F- V曲线呈凸型 ,| τt75 | <1s,τt2 5 ≈ 1s或 >1s,τt 关系呈“喇叭式”改变 ;3严重异常的 F- V曲线形状呈双曲线型 ,| τt75 | <1s,τt2 5 =4s～ 10 s,τt关系呈“塔式”改变。结论　双曲线型、τt2 5 极度延长和“塔式”改变是判断病情严重性的三大重要标志。该方法简便准确 ,利于在临床推广应用     

Pilot study of an HLA-A2 peptide vaccine using flt3 ligand as a systemic vaccine adjuvant

A pilot vaccine study was conducted to test the safety and immunological efficacy of four monthly immunizations of an MHC class I peptide vaccine, the E75 HLA-A2 epitope from HER-2/neu, using flt3 ligand as a systemic vaccine adjuvant. Twenty HLA-A2-expressing subjects with advanced stage prostate cancer were randomly assigned to one of four immunization or treatment schedules: (a) Flt3 ligand (20 g/kg per day) administered subcutaneously daily for 14 days on a 28-day cycle, monthly for four months; (b) flt3 ligand course as above with the E75 peptide vaccine administered on day 7 of each flt3 ligand cycle; (c) flt3 ligand course as above with the E75 peptide vaccine administered on day 14 of each flt3 ligand cycle; or (d) E75 peptide admixed with granulocyte–macrophage colony-stimulating factor and administered intradermally once every 28 days, as has previously been reported. The primary endpoints of the study were the determination of safety and immunological efficacy in generating E75-specific T cells as determined by peptide-specific interferon-gamma ELIspot. Adverse events included one grade 3 skin reaction and the development of grade 2 autoimmune hypothyroidism in two subjects with preexisting subclinical autoimmune hypothyroidism. Dendritic cells were markedly increased in the peripheral blood of subjects receiving flt3 ligand with each repetitive cycle, but augmentation of antigen-presenting cells within the dermis was not observed. Apart from a single subject, no significant peptide-specific T-cell responses were detected by ELIspot, whereas delayed-type hypersensitivity responses were detectable in control subjects and in subjects receiving peptide vaccine early in the course of flt3 ligand administration. The absence of robust peripheral immune responses in the current study may be attributable to the small numbers of subjects or differences in the subject population. In addition, the inability of flt3 ligand to augment the number of peripheral skin antigen-presenting cells may have contributed to the absence of robust peptide-specific immunity detectable in the peripheral blood of immunized subjects treated with flt3 ligand.     

干扰素－α对兔离体的卵巢颗粒细胞孕酮生成的影响

本研究应用离体培养的兔卵巢颗粒细胞观察了ＩＦＮ－ａ对孕酮生成的影响。细胞预培养２４ｈ后，用ＩＦＮ－ａ（５０～８００Ｕ／ｍｌ）处理培养的颗粒细胞１２ｂ刺激孕酮的生成并呈剂量依赖关系。在ＩＦＮ－ａ加入培养细胞后３、１２和２４ｈ．刺激作用非常明显，但刺激作用的幅度在３和１２ｈ较大，分别为对照组的２４和２０倍。此外，ＩＦＮ－ａ刺激离体兔颗粒细胞孕酮生成的作用被同时加钙螫合剂ＥＧＴＡ（１ｍｍｏｌ／Ｌ）或钙通道阻断剂异搏定（ｖｅｒ）２０和２００μｍｏｌ／Ｌ所抑制。本研究结果表明，ＩＦＮ－ａ刺激离体兔卵巢颗粒细胞孕酮的生成，其作用依赖于细胞外的Ｃａ２＋浓度。     

血栓闭塞性脉管炎患者血栓素、前列环素及血液流变学指标的检测分析

目的 :探讨血栓闭塞性脉管炎患者血栓素B2 、前列环素与血液流变学指标的变化及其与发病机制的关系。方法 :用放射免疫法测定TXA2 和PGI2 的代谢产物血栓素B2 (TXB2 )、6 酮 前列腺素F1α( 6 K PGF1α) ,LBY N6A自清洗旋转式粘度计测定血液流变学指标 ,并与对照组对比分析。结果 :血栓闭塞性脉管炎患者TXB2 ( 53.59± 83.2 1ng/L)、6 K PGF1α( 14 .50± 3.4 5ng/L) ,与对照组相比差异显著 ;全血高切粘度、低切粘度、血浆粘度及纤维蛋白原疾病组均高于对照组 ,差异具有统计学意义。结论 :血栓闭塞性脉管炎患者存在TXA2 /PGI2失衡 ,并与血液流变学的改变有密切关系     

The teaching of medicine at the University Centre for Health Sciences Yaounde,Cameroon: its concordance with the Edinburgh Declaration on Medical Education

Summary. The University Centre for Health Sciences (UCHS) or as it is referred to in French ‘Centre Universitaire des Sciences de la Santé’ (CUSS), became functional in 1969 with the enrolment of the first group of students. The objective of this training programme was to produce a scientifically sound, multipurpose doctor who would be fully operational in a rural setting with minimal equipment and supplies ( Monekosso 1970, 1972 ). The graduate had to be able to adapt readily to new situations and improvise whenever possible, calling for a high degree of competence and initiative. The training strategies adopted by UCHS in 1969 which met this requirement were later found to be in close concordance with the tenets of the World Conference on Medical Education held in Edinburgh in 1988, the Edinburgh Declaration. While some of the terminology may not have been worked out at the time, the programme developed embraced some new concepts hitherto untried or undeveloped:

• — the problem-solving approach in the first to the sixth year;
• — an integrated teaching approach during the first to sixth year of medical training;
• — an integrated medicine internship in district hospitals in the sixth year;
• — a community-based training approach throughout the training;
• — team training of three different health professionals;
• — competency-based training;
• — health services linked research;
• — health services linked training ( Monekosso & Quenum 1978 ).

The concordance of this programme to the Edinburgh Declaration is of great interest in realizing the World Federation for Medical Education programme and implementing the Edinburgh Declaration. The involvement of the three innovative medical schools in the planning stage of the curriculum explains this concordance.     

EB病毒LMP1在鼻咽癌细胞中通过IκBα的降解活化NF-κB

目的　阐明鼻咽癌细胞中EB病毒编码的潜伏膜蛋白 1(LMP1)活化核转录因子NF κB的机制。方法　利用强力霉素Dox诱导表达LMP1的鼻咽癌细胞株Tet on LMP1 HNE2为实验模型 ,首先应用免疫印迹方法测定Dox诱导后不同时相LMP1的表达动力学以及IκBs蛋白量及功能的改变。进而用间接免疫荧光法检测NF κB的亚细胞定位。最后采用瞬间共转染及报道基因活性分析分析NF κB的活性。结果　在鼻咽癌细胞Tet on LMP1 HNE2中 ,Dox处理 15分钟后LMP1的表达迅速升高并维持与较高水平直至 12 0分钟。LMP1的诱导性表达导致IκBα的磷酸化并降解 ,但IκBα蛋白总量无改变。继IκBα的磷酸化并降解 ,NF κB(P6 5 )自胞浆易位至胞核且活性升高。IκBα的显性负性突变子抑制NF κB(P6 5 )的核易位及报道活性。LMP1的诱导性表达并未引起IκBβ蛋白水平变化。结论　在鼻咽癌细胞Tet on LMP1 HNE2中 ,EB病毒LMP1通过IκBα的磷酸化并降解激活核转录因子NF κB的活性 ,并且 ,LMP1诱导的NF κB活性能被IκBα的显性负性突变子完全抑制。IκBβ在此信号传导途径中无改变。LMP1表达前后IκBα蛋白总量维持恒定可能是由于NF κB的活化迅速启动了IκBα的重头合成这一自身调节环路所致。