XIAP and P-glycoprotein co-expression is related to imatinib resistance in chronic myeloid leukemia cells

P-glycoprotein (Pgp) and XIAP co-expression has been discussed in the process of the acquisition of multidrug resistance (MDR) in cancer. Here, we evaluated XIAP and Pgp expression in chronic myeloid leukemia (CML) samples, showing a positive correlation between them. Furthermore, we evaluated the effects of imatinib in XIAP and Pgp expression using CML cell lines K562 (Pgp⁻) and K562-Lucena (Pgp⁺). Imatinib increased XIAP and Pgp expression in K562-Lucena cells, while in K562 cells a downregulation of these proteins was observed, suggesting that imatinib induces an increment of MDR phenotype of CML cells that previously exhibit high levels of Pgp/XIAP co-expression.     

Quantitative flow cytometry in the clinical laboratory

Flow cytometry is most often used in the clinical laboratory for the purpose of immunophenotyping. Here, fluorescently labeled antibodies are bound to cell surface receptors, and their presence on the cell is most often defined in bivariate terms of positive or negative, with a cutoff set relative to a nonstaining control population. It has long been recognized that the intensity of the fluorescent signal is proportional to the amount of antibody bound per cell and therefore related to the number of antigen sites expressed. This relationship makes flow cytometers, at least theoretically, capable of quantifying antigen expression in terms of molecules per cell. There were numerous obstacles to the development of such methods and clinical utilization of fluorescence intensity measures by flow cytometry has in the past been largely overlooked. The first widespread recognition of the clinical utility for fluorescence intensity measures came from laboratories where malignant phenotypes were defined by aberrant intensity of staining due to over or under expression of various cellular proteins. These semiquantitative measures were relative in nature and described staining as bright or dim compared to that normally seen in healthy individuals. Recent advances within the past decade have resulted in the development of flow cytometric methods and materials that now permit one to conduct measures of quantitative fluorescence with improved levels of control and interlaboratory precision. With these advances have come increasing interest in quantitative flow cytometry as a method to quantify the expression and activities of a variety of proteins and enzymes for diagnostic, prognostic, and therapeutic purposes. This article discusses the background and theoretical and practical considerations, as well as the current use of quantitative flow cytometry measures in the clinical laboratory.     

A possible role for maternal HLA antibody in a case of alloimmune neonatal neutropenia

BACKGROUND: Alloimmune neonatal neutropenia (ANN) is caused by a reaction of maternal alloantibodies with paternally inherited antigens on the fetal neutrophils. While human neutrophil antigens (HNA) antibodies are found in half of ANN cases, specific antibodies have not been defined in the remaining cases. STUDY DESIGN AND METHODS: Reported here is a neonate with omphalitis due to neutropenia. To elucidate the cause of ANN, flow cytometric and PCR analyses were used. Reactions of the patient's and mother's sera with neutrophils, lymphocytes, and platelets were examined by lymphocytotoxicity test (LCT), anti-human immunoglobulin-LCT, and mixed passive hemagglutination test. RESULTS: The maternal sera reacted with neutrophils, lymphocytes, and platelets of the patient and father. The platelet adsorption eliminated the reaction of the maternal serum with the patient's neutrophils. The HLA typing of the family and an LCT using a panel of lymphocytes of 20 HLA-typed donors showed HLA-A2 antigen as a target of antibodies in the maternal serum. According to anti-human immunoglobulin-LCT, the anti-HLA-A2 was present in the neonatal serum. On the other hand, HNA antibodies were not detectable in the patient's or the mother's serum. CONCLUSION: These results suggest that the transplacental passage of the maternal HLA antibody caused neutropenia in this patient.     

双侧低平延长型肾图定量分析的临床意义

肾实质性损伤稍重时,肾图即往往呈现奴侧低平延长型,并曾被称为“双侧无功能型肾图”。本方法作定性及定量分析证明以上观点是错误的,即使在肾功衰竭情况下,亦能检测出肾功能的存在并判断肾功受损程度。用RFI及REI作为肾功计量指标,与BUN之间呈显著的逆相关关系(P<0.01)。在肾功衰竭监护中,肾图是唯一不受透析治疗干扰而能真实地显示肾功能变化动态的肾功检查方法。本文阐述了这一分析方法及其临床意义。     

Frailty and the role of inflammation, immunosenescence and cellular ageing in the very old: cross-sectional findings from the Newcastle 85+ Study

Age-related frailty is an increasing societal challenge with growing emphasis on identifying its underlying pathophysiology and prospects for intervention. We report findings from the first comprehensive study of frailty and biomarkers of inflammation, immunosenescence and cellular ageing in the very old. Using cross-sectional data from the Newcastle 85+ Study (n = 845, aged 85), frailty was operationalized by the Fried and Rockwood models and biomarker associations explored using regression analysis. We confirmed the importance of inflammatory markers (IL-6, TNF-alpha, CRP, neutrophils) in frailty in the very old, previously established only in younger-old populations. Limited evidence was found for immunosenescence in frailty; although total lymphocyte count was inversely related, no association was found with the immune risk profile and the inverse associations observed with memory/naïve CD8 T and B cell ratios were in the opposite direction to that expected. We found no association with frailty in the very old for CMV sero-positivity, telomere length, markers of oxidative stress or DNA damage and repair. The Fried and Rockwood frailty models measure different albeit overlapping concepts yet biomarker associations were generally consistent between models. Difficulties in operationalizing the Fried model, due to high levels of co-morbidity, limit its utility in the very old.