不同中医证型肝硬化患者T细胞亚群NK细胞及补体系统检测的意义

目的:探讨不同中医证型肝硬化与血T细胞亚群、NK细胞、补体系统的关系。方法:对92例肝硬化患者进行中医分型,分为气滞湿阻型、肝脾血瘀型、脾肾阳虚型,并进行了外周血T细胞亚群、NK细胞以及补体C3、C4、B因子的测定;并设立正常对照组。结果:不同中医证型肝硬化的血CD3 、CD4 、CD4 /CD8 、NK细胞均有不同程度的降低,CD8 无明显变化;补体C3、C4、B因子均有不同程度的降低。结论:肝硬化的血T细胞亚群、NK细胞、补体系统存在着不同程度的变化,并与中医证型相关。     

Subject-by-Formulation Interaction in Bioequivalence: Conceptual and Statistical Issues

Purpose. The FDA has proposed replacing the current averagebioequivalence criterion with population and individual bioequivalence criteriathat consider variances in addition to the difference of averages. Oneof these variances in the individual bioequivalence criterion measuressubject-by-formulation interaction, the extent to which thetest-reference difference varies from person to person. This paper discussesconceptual and statistical issues raised in various publications andpresentations with respect to the presence and estimation of such aninteraction. Methods. We focus on the importance of subject-by-formulationinteraction, an understanding of what is a large interaction, and theassessment of the magnitude of this interaction in bioequivalence studies.Simulation studies, examples from the literature, and data from FDAfiles are used to demonstrate the magnitude of the interaction and itsdistribution under various conditions. Results. The concept of a large interaction is tied to the concept of alarge mean difference. We suggest that an interaction greater than0.15 is a conservative criterion for a large interaction. Magnitudes ofestimated interaction are affected by variability, sample size, and theselection of data sets that pass average bioequivalence. Conclusions. Examples of substantial interactions are beginning toappear. More data is needed before reaching definitive conclusionsregarding the frequency and importance of observed interactions.     

Novel glycolipid variations revealed by monoclonal antibody immunochemical analysis of weak ABO subgroups of A

BACKGROUND AND OBJECTIVES: The chemical basis of the subgroups of A is largely unknown. We used thin-layer chromatography immunochemical staining techniques together with a range of characterized monoclonal reagents to analyse glycolipids isolated from a variety of weak subgroups. MATERIALS AND METHODS: Glycolipids isolated from red cells collected from nine genetically defined individuals of the rare subgroups of A, including a novel A(3) allele (A(2) 539G>A) not described previously, were subjected to a highly sensitive thin-layer chromatographic immunochemical analysis. RESULTS: Semicharacterized monoclonal antibodies revealed that, in addition to the expected quantitative differences between common phenotypes and the weak subgroups, qualitative glycolipid differences (or at least an apparent qualitative basis), caused by major changes in the ratios of different structures exist. Specifically it was found that the weakest A-expressing samples (A(el) phenotype) appeared to express an unusual A structure in the 8-12 sugar region. Variable expression of several structures in one of the A weak samples were suggestive of novel blood group A structures. CONCLUSIONS: Although no structural characterization could be undertaken, the results are clearly indicative that the variant glycosyltransferases of the rare ABO subgroups are not only inefficient, but they may potentially synthesize novel ABO structures.     

Statistical issues in interpreting clinical trials

Randomized clinical trial is an important research tool in evaluating new therapeutic agents, devices and procedures. In order to obtain reliable and unbiased results, careful consideration must be given in the design and conduct of the trial. However, bias can be introduced in the analysis of the final data if certain principles are not followed. Several issues are described that make interpretation of analyses challenging. These include the intent-to-treat principle, the use of surrogate outcome measures, subgroup analyses, missing data and noninferiority trials.     

Heterogeneity of lymphoblastic malignancies in children

Summary Lymphocyte surface markers show that lymphoblastic lymphomata in children are a heterogeneous but related group of diseases. Lymphoblastic lymphomas of T cell type fall into at least three subgroups: (1) HTLA positive, E rosette negative, TdT positive phenotype, with characteristically high levels of TdT and some associated expression of C-ALL antigen on a small proportion of cells. (2) E rosette positive lymphoblasts with intermediate range of TdT positivity, and which express antigens specific for thymic cortical lymphocytes. (3) E rosette positive and C3d positive T lymphoblasts with low levels of TdT enzyme.B lymphoblastic lymphomas show a major subgroup characterised by surface IgM expression, with or without detectable cytoplasmic IgM, and which may express ALL antigen. A minor subgroup of B lymphoblastic disease, of predominantly nodal presentation, expresses surface IgM with some expression of C3d receptors. Therefore at least 3 T cell, and 2 B cell subgroups of lymphoblastic lymphoma can be described.     

恶性肿瘤患者外周血淋巴细胞高效体外扩增的方法

探讨从恶性肿瘤患者外周血单个核细胞（PBMCs）中高效扩增淋巴细胞的方法,取3例恶性肿瘤患者的PBMCs,每例患者重复3次,在GMP实验室体系下,经淋巴细胞刺激因子体外诱导扩增淋巴细胞和观察扩增情况,应用流式细胞仪分析扩增前后总CD3^＋、CD3^＋CD4^＋、CD3^＋CD8^＋淋巴细胞、CD3^＋CD16＋56^＋（NK细胞）、CD3^＋CD16＋56^＋（NKT细胞）以及CD4^＋和CD8^＋T细胞比值的变化,分析培养前后各淋巴细胞亚群的扩增情况和重复性,同时观察淋巴细胞体外扩增培养后回输患者的生物安全性。结果表明,CD3^＋、CD3^＋CD8^＋、CD3^＋CD16＋56^＋细胞比例较培养前明显增加（P〈0．01）,而CD3^＋CD^＋、CD3^-CD16＋56^＋细胞比例、CD^＋和CD8^＋T细胞比值则明显的降低（P〈0．01）。CD3^＋、CD3^＋CD8^＋、CD3^＋CD16＋56^＋细胞增殖倍数的中位数分别为487．9、832．5和2540．6;而CD3^＋CD4^＋和CD3^＋CD16＋56^＋则分别为159．6和155．5。细胞体外扩增培养前后亚型和扩增倍数的重复性较差,在本研究中只有CD3^＋T细胞在体外培养前后、CD3^＋CD16＋56^＋细胞在培养后的CV值在10％以内。培养扩增后淋巴细胞细菌、真菌、支原体、外来病毒及内毒素检查后无阳性发现,所有患者细胞回输治疗后无明显的毒副反应。在本研究体系下体外诱导扩增培养肿瘤患者自体外周血NK细胞及致敏淋巴细胞效率较高,细胞毒性细胞比例增高较大,具有良好的生物安全性,为恶性肿瘤患者应用NK细胞进行过继免疫治疗提供了一种简单有效的扩增NK细胞的方法。     

Interphase fluorescence in situ hybridization analysis detects a much higher rate of thyroid tumors with clonal cytogenetic deviations of the main cytogenetic subgroups than conventional cytogenetics

In benign thyroid lesions, three main cytogenetic subgroups, characterized by trisomy 7 or structural aberrations involving either chromosomal region 19q13.4 or 2p21, can be distinguished by conventional cytogenetics (CC). As a rule, these aberrations seem to be mutually exclusive. Interphase fluorescence in situ hybridization (I-FISH) analysis on benign as well as malignant thyroid neoplasias has been performed in the past, but rarely in combination with CC. In the present paper, we have analyzed 161 benign thyroid lesions both with CC and I-FISH on touch preparations by using a multi-target, triple-color FISH assay as well as dual-color break-apart probes for detection of the main cytogenetic subgroups. Within the samples, I-FISH detected tumors belonging to either of the subgroups more frequently than CC (23 vs. 11.4%), either due to small subpopulations of aberrant cells or to cryptic chromosomal rearrangements (three cases). Thus, I-FISH seems to be more sensitive than CC, particularly in the detection of subpopulations of cells harboring cytogenetic aberrations that may be overlooked by CC. In summary, I-FISH on touch preparations of benign thyroid lesions seems to be a favorable method for cytogenetic subtyping of thyroid lesions.     

肺炎支原体肺炎患儿T细胞亚群变化及匹多莫德的治疗作用

目的:探讨肺炎支原体患儿T细胞亚群变化及匹多莫德的治疗作用。方法:68例支原体肺炎患儿随机分为两组,两组均予静脉点滴阿齐霉素5天后,予以阿齐霉素口服,剂量和疗程相同。治疗组加匹多莫德口服,而对照组不用。采用流式细胞仪(FCM)检测68例支原体肺炎患儿外周血T细胞亚群,并以28例健康儿童作为正常对照。结果:支原体肺炎急性期外周血CD4+T细胞比例、CD4+/CD8+T细胞比值分别为(32.40±5.93)%和(1.12±0.43),与正常对照组相比明显下降(P<0.01);CD8+T细胞比例为(28.96±3.34)%,与正常对照组相比显著升高(P<0.01)。支原体肺炎患儿经匹多莫德治疗后外周血CD4+T细胞比例和CD4+/CD8+T细胞比值有明显上升(P<0.05);未经匹多莫德治疗的支原体肺炎患儿在治疗前后T细胞亚群各项指标均无显著性变化。支原体肺炎患儿匹多莫德治疗组平均病情反复次数较非匹多莫德治疗对照组明显下降(P<0.05)。结论:肺炎支原体肺炎患儿T细胞免疫功能低下,匹多莫德可提高机体免疫功能,对支原体肺炎的治疗有重要的临床意义。     

Role of the subgroups of T,B, natural killer lymphocyte and serum levels of interleukin‐15, interleukin‐21 and immunoglobulin E in the pathogenesis of urticaria

The immunological characterization in the pathogenesis of urticaria, mainly regarding cytokine profile, needs more investigation. In this study, subgroups of the T, B and natural killer (NK) lymphocyte from peripheral blood and serum levels of interleukin (IL)‐15, IL‐21 and immunoglobulin (Ig)E were examined in patients with acute urticaria (AU) and chronic urticaria (CU). Moreover, symptom scores and course of the patients were assessed. The percentage of NK cells and the ratio of CD4⁺/CD8⁺ increased, however, CD8⁺ decreased in CU compared to controls (P < 0.01). But no significant changes of T, B and NK lymphocyte were found in AU. IL‐15 and IL‐21 significantly decreased in AU and CU, but IgE increased. CU with a positive autologous serum skin test were more likely to be associated with longer course and higher CD3⁺, B cells and IL‐21, and lower IgE (P < 0.01). Weak negative correlations were demonstrated between CD3⁺, CD8⁺ and scores in CU (r = ?0.23, ?0.25, P < 0.05). Significant correlations were found between B cells and scores and course in CU (r = 0.49, 0.65, P < 0.01). Moreover, a significant correlation was found between IL‐21 and IgE (r = 0.42, P < 0.01) in CU. But no significant correlations were found in AU. Our findings supported the concept that both humoral immunity and cellular immunity dysregulation in the pathogenesis of urticaria – mainly related to the decrease of the serum levels of IL‐15 and IL‐21 – may induce the increasing expression of IgE produced by B cells.