急性白血病T淋巴细胞及其亚群的研究

应用McAb检测31例急性白血病患者外周血T细胞及其亚群的改变。结果表明总T细胞(T_1)、T辅助细胞(T_4)和T抑制细胞(T_8)百分率均明显低于正常对照组(P<0.01～0.001),且伴有T_4:T_8值的下降(P<0.05)。经化疗缓解后,部分缓解组T细胞及其亚群均恢复正常,完全缓解组T_4细胞仍稍低于正常值(P<0.05)。化疗无效组T细胞及其亚群的改变与未治疗组类似(P>0.05)。急淋T-ALL型时,外周血T细胞及其亚群的改变与一般白血病表现不同,其T细胞标记及T_4:T_8值反而增高。病情缓解时逐渐恢复正常急淋其它型患者,其T细胞及亚群的改变与急非淋患者类似。结果提示,动态观察T细胞及其亚群变化,有助于对白血病患者疗效及预后的判定。     

不同诱导化疗治疗急性淋巴细胞白血病分析

目的对比不同化疗方案治疗成人急性淋巴细胞白血病效果。方法将患有急性淋巴细胞白血病的50例患者,随机分为VDLP组25例和VTLP组25例。分别行VDLP和VTLP化疗治疗。结果对两组患者治疗后CR（完全缓解率）进行比较：VDLP组为84.0%,VTLP组为88.0%,无明显差异（P〉0.05）;比较两组患者完全缓解所需时间显示：VTLP组患者完全缓解所需时间为15~68天,VDLP组患者完全缓解所需时间为21~102天,差异明显（P〈0.05）,具有统计学意义。结论行化疗方法治疗成人急性淋巴细胞白血病方面,VTLP疗法完全缓解所需时间明显低于VDLP疗法,值得在临床广泛应用。     

Ph染色体在急性淋巴细胞白血病中的诊断

目的：探讨Ph染色体在急性淋巴细胞白血病中的诊断意义。方法选取2013年4月～2014年4月由我院血液科收治的24例成人初治急性淋巴细胞白血病患者和10例慢粒急淋变患者为研究对象。使用改良的染色体显带技术对患者的Ph染色体进行检测,回顾性分析34例患者染色体核型检测过程和检测结果。结果使用改良的染色体显带技术对34例急性淋巴细胞白血病患者进行Ph染色体的检测,检测出25例患者的ph染色体呈阳性,总检出率为73.5%,其中初治急性淋巴细胞白血病患者16例,检出率为66.7%,低于慢粒急淋变患者90%的检出率,两者在比较上,差异具有统计学意义（P＜0.05）。结论对急性淋巴细胞白血病患者采用染色体显带技术对Ph染色体进行监测,其检出率高,对ph染色体有一定的灵敏度,可作为临床急性淋巴细胞白血病的诊断标准。     

无关供者骨髓移植治疗多次复发性急性白血病

文章探讨无关供者骨髓移植治疗多次复发急性白血病的疗效 .经改良 Bucy方案预处理后对一例第三次复发的急粒患者行无关供者骨髓移植 ,同时给防治 GVHD、抗感染治疗 .结果 + 2 1天骨髓在患者体内植活 ,+ 35天细胞染色体分析呈供者型 ( 4 6,XX.正常核型 ) ,+ 84天血型转换成供者型 ,至今已无病生存超过 6个月 .结果表明 ,无关供者骨髓移植对多次复发的急性白血病患者具有治疗价值     

淋系白血病中人类疱疹病毒6型的感染情况

目的 :了解淋巴系统白血病患者人类疱疹病毒 - 6型 (HHV - 6)的感染情况。方法 :患者 38例 ,包括急性淋巴细胞白血病 (ALL) 31例、慢性淋巴细胞白血病 (CLL) 4例、淋巴瘤白血病 (LL) 3例 ,正常对照 38例。取抗凝外周血 ,分离单个核细胞 ,提取DNA ,用巢式PCR方法检测目标DNA。结果 :HHV - 6DNA阳性检出率在全部患者中为 63% ,其中在ALL患者中为 68% ,均明显低于正常对照的阳性检出率 92 % (P <0 .0 5 ) ,另外 ,4例CLL患者有 1例阳性 ,3例LL患者中 2例阳性。结论 :在淋巴系统恶性疾病中HHV - 6的感染率低于正常人群 ,其临床意义有待进一步研究。     

建立Raji细胞免疫酶抑制法对血清抗HLA—DR抗体的检测

由于Raji细胞表面具有表达HLA-DR抗原特点,利用被测血清中抗HLA-DR抗体与抗人HLA-DR单克隆抗体竞争和Raji细胞表面HLA-DR抗原结合的特征,建立了Raji细胞免疫酶抑制法检测血清中抗HLA-DR抗体的方法。进行了方法学特异性,重复性和实验条件确定研究,并用此方法检测了72例系统性红斑狼疮患者和113例健康者血清。结果显示:该方法特异性强(中性粒细胞无显色反应);重复性好(抗体阳性血清变异率C.V为4.66％,抗体阴性血清C.V为0％);抗体滴度范围1∶5-1∶40。系统性红斑狼疮患者中抗HLA-DR抗体阳性率为30％;而健康阳性率为1.8％。作者认为:用Raji细胞免疫酶抑制法检测血清中抗HLA-DR抗体是一种特异性强,重复性好,操作简便和假阳性率低的方法,这种方法值得推广应用。     

PCR检测白血病患者外周血中EB病毒的DNA

目的：了解白血病患者ＥＢ病毒感染情况。方法：收集２１例急性淋巴细胞白血病、１例慢性淋巴细胞白血病、１５例急性粒细胞白血病、８例慢性粒细胞白血病患者及３２例正常对照组的外周血,分离单个核细胞,提取ＤＮＡ,应用ＰＣＲ方法检测ＥＢ病毒ＤＮＡ。结果：在１例初诊慢性粒细胞白血病病人样本中发现ＥＢ病毒阳性,余均为阴性。结论：白血病患者存在ＥＢ病毒感染情况,但并不普遍。     

淋系白血病人类疱疹病毒6型的感染情况

目的：了解淋巴系统白血病患者人类疱疹病毒－6型（HHV－6）的感染情况。方法：患者38例,包括急性淋巴细胞白血病（ALL）31例、慢性淋巴细胞白血（CLL）4例、淋巴瘤白血病（LL）3例,正常对照38例。取抗凝外周血,分离单个核细胞,提取DNA,用巢式PCR方法检测目标DNA。结果：HHV－6DNA阳性检出率在全部患者中为63％,其中在ALL患者中为68％,均明显低于正常对照的阳性检出率92％（P＜0．05）。另外,4例CLL患者有1例阳性,3例LL患者中2例阳性。结论：在淋巴系统恶性疾病中HHV－6的感染率低于正常人群,其临床意义有待进一步研究。     

三分类血液分析仪与血涂片镜检对白血病患者血液细胞分类结果差异分析

目的 探讨诊断白血病更准确、更全面的方法.方法 采用血液分析仪和手工涂片分类法同时诊断白血病.结果 14例ALL患者仪器不能进行白细胞分类和幼稚细胞提示;6例APL患者仪器进行了错误分类;24例AML患者仪器将血液中的幼稚细胞错误分类为小型白细胞;8例CML患者仪器将血液中的幼粒细胞及嗜酸嗜碱细胞分类为中间细胞群,以上均与手工分类有很大差异.结论 通过对56例白血病患者的血液分析,证实了在初诊白血病患者血样分析中,仪器不能给予白细胞分类及幼稚细胞的识别,对多形态、多变化性的血细胞识别有限.因此,用血液分析仪分析血样的同时,不能忽略血细胞形态学检查,防止幼稚细胞漏检.     

50例急性白血病细胞电镜研究

用电镜和光镜相结合观察50例急性白血病,两者诊断符合率达90%,电镜有助于急性白血病的诊断分型,SEM 下急粒以嵴样型细胞为多,占48～90%;急单中的皱膜型细胞为70～81%;急淋白血病细胞表面特征主要有光滑型和微绒毛型两种.TEM 观察结果和既往作者报道的相似.     

蛋白激酶C单克隆抗体的制备

应用杂交瘤技术制备了蛋白激酶C(PKC)的单克隆抗体,用蛋白A-Sepharose-CL4B协同沉淀复合物分析单抗识别的蛋白,分子质量与PKC相同。采用该抗体对正常和转化的C_3H_(10) T_(1/2)细胞进行免疫荧光观察,发现它们的PKC含量明显不同。但荧光分布都主要集中在细胞质和细胞膜部分。     

HLA-DQ is epistatic to HLA-DR in controlling the immune response to schistosomal antigen in humans

Antigens that produce an antibody response in some members of a species may fail to do so in others. The response to an antigen is controlled by a gene termed the immune response (Ir) gene, which is transmitted as a single dominant trait. We have provided evidence for similar immune suppression (Is) genes which control non-responsiveness through the antigen specific suppressor T cell. The non-responsiveness is also dominantly inherited and the Is genes are linked to the histocompatibility (HLA) antigen system. Here we report that the HLA-DR2 molecule from a non-responder haplotype (HLA-Dw12-DR2-DQwl) is required for the proliferative T cell response to schistosoma japonicum (Sj) antigen, as a restriction element, indicating that the HLA-DR2 is the product of the Ir gene, and that the HLA-DQwl molecule of the non-responder haplotype is important in the antigen-specific suppression of the response to this antigen, suggesting that it is the product of the Is gene. We therefore conclude that the HLA-DR and DQ molecules, which are controlled by the distinct genes in the MHC multigene family, regulate immune response and immune suppression and that the gene for HLA-DQ is epistatic to that for HLA-DR in controlling the immune response to schistosomal antigen in humans.     

Expression of cell-surface HLA-DR, HLA-ABC and glycophorin during erythroid differentiation

The unexpected discovery that Ia-like (HLA-DR) antigens in humans were present on blast cells from acute myeloblastic leukaemia led to the finding that normal granulocytic progenitors, in contrast to their mature descendents, also expressed HLA-DR antigens. Thus, anti-Ia sera stain a proportion of myeloblasts in normal bone marrow, inhibit myeloid progenitor (CFU-GM) colony formation in the presence of complement and can be used to label and separate CFU-GM on a fluorescence-activated cell sorter (FACS). Winchester et al. subsequently reported that erythroid progenitors (BFU-E and CFU-E) were also inhibited or killed by anti-Ia (p28,37) and complement. These observations raised the possibility that HLA-DR (or presumptive I-region equivalent) products might have a regulatory role in early haematopoiesis. We have now analysed HLA-DR and HLA-ABC antigen expression on normal erythroid progenitors using monoclonal antibodies to non-polymorphic determinants and fluorescence-activated cell sorting. In parallel experiments, we tested a monoclonal antibody to glycophorin, a well defined erythroid-specific cell-surface membrane glycoprotein. We report that HLA-DR, HLA-ABC and glycophorin are all expressed at various stages during erythroid differentiation.     

HLA-DR products are a subset of human Ia antigens

Human Ia antigens are polymorphic cell-surface sialoglycoproteins which have restricted tissue distribution. They are bimolecular complexes of 34,000 (alpha) and 28,000 (beta) molecular weight and most of the polymorphism is found in the smaller polypeptides. They are involved in the initiation of immune responses and particular Ia antigens are associated with increased susceptibility to certain diseases. They are also the major barrier to human allogeneic tissue transplantation. Whereas serological analysis and mixed lymphocyte typing have defined three polymorphic families of Ia antigens, HLA-DR, -DC and -SB, protein sequencing results and studies with monoclonal antibodies indicate that the complexity is much greater. Thus the HLA-DR and DC specificities as defined by alloantisera, could represent groups of antigens which are controlled by HLA genes in linkage disequilibrium. Here, we have used a monoclonal antibody specific for HLA-DR2 to show that this determinant is carried by molecules which are distinct from those of the DC series and which represent 30% of the Ia antigens expressed on the cell surface of an HLA homozygous line PGF.     

人正常子宫内膜树突状细胞的周期性变化

目的：研究人正常子宫内膜上树突状细胞(dendritic cell，DC)的分布特点。方法：对10例人正常子宫内膜组织应用HLA-DR单克隆抗体和CD1a蛋白抗体进行免疫组化染色，其中增殖期内膜4例、分泌期内膜3例、绝经期内膜3例，观察其中的阳性细胞。结果：10例正常子宫内膜标本中，5例呈HLA-DR阳性表达(增殖期4例，分泌期1例，绝经期0例)；4例呈CD1a阳性表达(增殖期3例，分泌期1例，绝经期0例)。结论：人正常子宫内膜组织中存在表达主要组织相容性复合体-Ⅱ(MHC-Ⅱ)类分子的DC，各时期的子宫内膜DC检出率不同。     

HLA-D region beta-chain DNA endonuclease fragments differ between HLA-DR identical healthy and insulin-dependent diabetic individuals

The human HLA-D histocompatibility region encodes class II antigens each of which consists of two polypeptide chains (alpha and beta) inserted in the plasma membrane. These molecules are implicated in the regulation of the immune response but several human diseases are also found to be associated with certain HLA-DR antigens. The occurrence of insulin-dependent (type I) diabetes (IDDM) is strongly associated with HLA-DR3 and/or 4 (ref. 5). The class II antigens, however, show a marked genetic polymorphism associated with the beta-chains which seem, from hybridization studies, to be encoded by several genes. We have therefore used the beta-chain cDNA probe, pDR-beta-1 (refs 8, 10) to test whether there are differences in hybridization pattern between DNA from healthy individuals and diabetic patients, after digestion with restriction endonucleases. Among the HLA-DR 4 and 3/4 individuals, the IDDM patients showed an increased frequency of a PstI 18 kilobase (kb) fragment. A BamHI 3.7 kb fragment, frequent among controls (30-40%), was rarely detected in the IDDM patients (0-2%). These differences may be related to susceptibility to develop the disease.     

Polyreactivity increases the apparent affinity of anti-HIV antibodies by heteroligation

During immune responses, antibodies are selected for their ability to bind to foreign antigens with high affinity, in part by their ability to undergo homotypic bivalent binding. However, this type of binding is not always possible. For example, the small number of gp140 glycoprotein spikes displayed on the surface of the human immunodeficiency virus (HIV) disfavours homotypic bivalent antibody binding. Here we show that during the human antibody response to HIV, somatic mutations that increase antibody affinity also increase breadth and neutralizing potency. Surprisingly, the responding naive and memory B cells produce polyreactive antibodies, which are capable of bivalent heteroligation between one high-affinity anti-HIV-gp140 combining site and a second low-affinity site on another molecular structure on HIV. Although cross-reactivity to self-antigens or polyreactivity is strongly selected against during B-cell development, it is a common serologic feature of certain infections in humans, including HIV, Epstein-Barr virus and hepatitis C virus. Seventy-five per cent of the 134 monoclonal anti-HIV-gp140 antibodies cloned from six patients with high titres of neutralizing antibodies are polyreactive. Despite the low affinity of the polyreactive combining site, heteroligation demonstrably increases the apparent affinity of polyreactive antibodies to HIV.     

Polymorphism of human Ia antigens: gene conversion between two DR beta loci results in a new HLA-D/DR specificity

The polymorphic HLA-DR beta-chains are encoded within the human major histocompatibility complex (MHC) by multiple loci resulting from gene duplications. Certain DR haplotypes can be grouped into families based on shared structural factors. We have studied the molecular basis of HLA-DR polymorphism within such a group which includes the haplotypes DR3, DR5 and DRw6. Molecular mapping of the DR beta-chain region allows true allelic comparisons of the two expressed DR beta-chain loci, DR beta I and DR beta III. At the more polymorphic locus, DR beta I, the allelic differences are clustered and may result from gene conversion events over very short distances. The gene encoding the HLA-DR3/Dw3 specificity has been generated by a gene conversion involving the DR beta I and the DR beta III loci of the HLA-DRw6/Dw18 haplotype, as recipient and donor gene, respectively. Based on which allele is found at DR beta III, the less polymorphic locus, two groups of haplotypes can be defined: DRw52a and DRw52b. The generation of HLA-DR polymorphism within the DRw52 supertypic group can thus be accounted for by a succession of gene duplication, divergence and gene conversion.     

人类巨细胞病毒感染致1型糖尿病机制的初步探讨

目的通过对1型糖尿病患者的HCMV感染标志物、空腹血糖、空腹C肽、胰岛素自身抗体及抗胰岛细胞抗体的研究,初步探讨HCMV致1型糖尿病的机制。方法检测1型糖尿病患者的HCMV感染标志物（包括HCMV—IgG及其相对含量、HCMV—IgM及HCMV—pp65）、空腹血糖、C肽、抗胰岛素自身抗体及抗胰岛细胞抗体并进行统计学分析。结果HCMV感染与1型糖尿病患者抗胰岛素自身抗体之间无明显相关性,但与1型糖尿病患者空腹血糖、空腹C肽、抗胰岛细胞抗体存在明显的相关性,HCMV—pp65阳性的1型糖尿病患者中其空腹血糖明显高于该指标阴性者;抗HCMV—IgG阳性的1型糖尿病患者空腹血糖水平、抗胰岛细胞抗体均显著高于抗HCMV—IgG阴性者,而空腹C肽水平则明显低于抗HCMV—IgG阴性者,且抗HCMV—IgG抗体指数在4．1以上者,其抗胰岛细胞抗体阳性率显著高于抗HCMV—IgG抗体指数在4．0以下者。结论HCMV感染可能通过直接损伤胰岛免疫病理反应损伤胰岛细胞最终导致1型糖尿病的发生。