工程化视知觉感知学习系统治疗儿童弱视的效果评价

目的:传统治疗弱视的方法(如遮盖治疗,精细训练等)起效慢,疗效欠佳;视知觉感知学习系统作为一种针对性很强的儿童弱视治疗方法,其疗效需进一步观察。方法:①收集2006-09/2007-02于广西壮族自治区人民医院视光中心就诊的弱视儿童125例250眼,女73例,男52例,年龄(6±2)岁。患儿家长知情同意并签署知情同意书;实验经医院伦理委员会批准。②根据视功能检查结果,采用视知觉感知学习系统对弱视患儿进行针对性的治疗,如双眼视力相差两行以上,辅助遮盖优势眼治疗。1个月为1个疗程,每天训练2次,每次2个训练内容(程序),每个训练内容10min,40min/d,训练内容之间要求有10min左右的休息间隙。训练需在安静和黯淡环境下进行。每月定期复查双眼视力及其各项视功能的恢复情况,并根据复查结果继续原程序治疗或调整治疗程序。结果:弱视患儿125例均进入结果分析。①视力:视知觉感知学习系统治疗儿童弱视的总有效率为75.2%,视力提高行数从治疗第3个月起有大幅增加(P<0.05),最佳矫正视力由治疗前的0.60±0.23提高至治疗后的0.86±0.26,差异有显著性意义(P<0.05)。②治疗时间与疗效:疗效达到进步的平均时间为(2.82±1.30)个月,达到基本治愈为(2.87±1.40)个月。治疗3个月的患者视力疗效达进步率最高[98%(39/40)],治疗1个月的患者视力进步率最低[55%(31/56),P<0.05]。基本治愈率随治疗时间的增加递增,治疗4个月组基本治愈率最高[67%(31/46),P<0.05]。结论:视知觉感知学习系统治疗儿童弱视疗效快,达到有效的时间为治疗两三个月。     

颈动脉内中膜厚度与初诊2型糖尿病视网膜病变的关系

目的:研究发现,糖尿病视网膜病变和动脉粥样硬化终点事件相关。试验拟验证颈动脉内中膜厚度与初诊汉族2型糖尿病患者糖尿病视网膜病变相关危险因素的关系。方法:①试验对象:选择2006-06/2007-06本院住院的初诊2型糖尿病患者187例,男114例,女73例;平均年龄(51±14)岁;平均体质量指数(24.7±4.7)kg/m2。均符合1997年美国糖尿病协会的2型糖尿病诊断标准,排除既往已存在心血管疾病者。患者对治疗及试验均知情同意。根据眼底照相检查结果,将所有受检者分为糖尿病视网膜病变组及非糖尿病视网膜病变组进行统计分析。②试验方法及评估:所有患者询问一般情况,测量颈动脉内中膜厚度以及相关生化指标,对糖尿病视网膜病变相关因素进行单因素及多因素Logistic回归分析。结果:纳入2型糖尿病患者187例,均进入结果分析。单因素Logistic回归分析显示,高血压、糖尿病家族史、颈动脉内中膜厚度、尿白蛋白、低密度脂蛋白胆固醇与糖尿病视网膜病变发生呈显著正相关,多因素Logistic回归分析未见显效因素。结论:单因素回归分析中颈动脉内中膜厚度及其他4项指标与糖尿病视网膜病变相关,而多因素回归分析这些因素未进入主效基因模型。     

Concurrent detection of minimal residual disease (MRD) in childhood acute lymphoblastic leukaemia by flow cytometry and real-time PCR

Minimal (i.e. submicroscopic) residual disease (MRD) predicts outcome in childhood acute lymphoblastic leukaemia (ALL). To be used clinically, MRD assays must be reliable and accurate. Two well-established techniques, flow cytometry (FC) and polymerase chain reaction (PCR), can detect leukaemic cells with a sensitivity of 0.01% (10(-4)). We analysed diagnostic samples of 45 ALL-patients (37 B-lineage ALL, eight T-lineage ALL) by four-colour FC and real-time PCR. Leukaemia-associated immunophenotypes, at a sensitivity of MRD detection by FC at the 0.01% level, were identified in 41 cases (91%); antigen-receptor gene rearrangements suitable for MRD detection with a sensitivity of 0.01% or better by PCR were identified in 38 cases (84%). The combined use of FC and PCR allowed MRD monitoring in all 45 patients. In 105 follow-up samples, MRD estimates by both methods were highly concordant, with a deviation factor of <5 by Bland-Altman analysis. Importantly, the concordance between FC and PCR was also observed in regenerating bone marrow samples containing high proportions of CD19(+) cells, and in samples studied 24 h after collection. We conclude that both MRD assays yield generally concordant results. Their combined use should enable MRD monitoring in virtually all patients and prevent false-negative results due to clonal evolution or phenotypic shifts.     

Erythropoietin promotes Schwann cell migration and assembly of the provisional extracellular matrix by recruiting β1 integrin to the cell surface

In peripheral nerve injury, Schwann cells undergo profound phenotypic modulation, adopting a migratory phenotype and remodeling the extracellular matrix so that it is permissive for axonal regrowth. Erythropoietin (Epo) and its receptor (EpoR) are expressed by Schwann cells after nerve injury, regulating inflammatory cytokine expression and minimizing the duration of neuropathic pain. The mechanism of Epo activity in the injured peripheral nerve remains incompletely understood. Herein, we demonstrate that Epo promotes Schwann cell migration in vitro on fibronectin (FN)‐coated surfaces. Epo also rapidly recruits β1 integrin subunit to the Schwann cell surface by a JAK‐2‐dependent pathway. Although β1 integrin subunit‐containing integrins were not principally responsible for Schwann cell adhesion or migration on FN under basal conditions, β1 gene‐silencing blocked the ability of Epo to promote cell migration. Epo also induced Schwann cell FN expression in vitro and in vivo. The FN was organized into insoluble fibrils by Epo‐treated Schwann cells in vitro and into an extensive matrix surrounding Schwann cells in vivo. Our results support a model in which Epo promotes Schwann cell migration and assembly of the provisional extracellular matrix in the injured peripheral nerve by its effects on integrin recruitment to the cell surface and local FN production. © 2009 Wiley‐Liss, Inc.     

Polarization dictates iron handling by inflammatory and alternatively activated macrophages

Background

Macrophages play a key role in iron homeostasis. In peripheral tissues, they are known to polarize into classically activated (or M1) macrophages and alternatively activated (or M2) macrophages. Little is known on whether the polarization program influences the ability of macrophages to store or recycle iron and the molecular machinery involved in the processes.

Design and Methods

Inflammatory/M1 and alternatively activated/M2 macrophages were propagated in vitro from mouse bone-marrow precursors and polarized in the presence of recombinant interferon-γ or interleukin-4. We characterized and compared their ability to handle radioactive iron, the characteristics of the intracellular iron pools and the expression of molecules involved in internalization, storage and export of the metal. Moreover we verified the influence of iron on the relative ability of polarized macrophages to activate antigen-specific T cells.

Results

M1 macrophages have low iron regulatory protein 1 and 2 binding activity, express high levels of ferritin H, low levels of transferrin receptor 1 and internalize – albeit with low efficiency -iron only when its extracellular concentration is high. In contrast, M2 macrophages have high iron regulatory protein binding activity, express low levels of ferritin H and high levels of transferrin receptor 1. M2 macrophages have a larger intracellular labile iron pool, effectively take up and spontaneously release iron at low concentrations and have limited storage ability. Iron export correlates with the expression of ferroportin, which is higher in M2 macrophages. M1 and M2 cells activate antigen-specific, MHC class II-restricted T cells. In the absence of the metal, only M1 macrophages are effective.

Conclusions

Cytokines that drive macrophage polarization ultimately control iron handling, leading to the differentiation of macrophages into a subset which has a relatively sealed intracellular iron content (M1) or into a subset endowed with the ability to recycle the metal (M2).     

Natural killer cell engineering for cellular therapy of cancer

Natural killer (NK) cells can kill transformed cells and represent a promising tool for the treatment of cancer. Their function is governed by a balance of stimulatory and inhibitory signals triggered by surface receptors. Advances in NK cell therapy require the development of dependable methods for obtaining an adequate number of effector cells; additional activation or genetic modification may further increase their anticancer capacity. A method for NK cell expansion used in our laboratory relies on a genetically modified form of the K562 myeloid leukemia cell line, engineered to express a membrane-bound form of interleukin-15 and the ligand for the costimulatory molecule 4-1BB (CD137). Expanded NK cells can be transduced with genes encoding chimeric antigen receptors that stimulate tumor cell-specific cytotoxicity. These methods for NK cell expansion and genetic modification have been adapted to large-scale, clinical-grade, Current Good Manufacturing Practice conditions and support two active clinical trials. Summarized are current efforts for NK cell immunotherapy for cancer and future perspectives.     

Detection of first- and second-order coherent motion in blindsight

Blindsight patients can detect fast moving stimuli presented within their blind field even when they deny any phenomenal visual experience. Although mounting evidence suggests the presence of different mechanisms and separate neural substrates underlying the processing of first-order (luminance-defined) and second-order (contrast-defined) motion, the perception of second-order motion in blindsight has scarcely been explored. In the present study, we investigated whether two blindsighted patients (GY and MS) can detect a variety of first- and second-order moving stimuli, and by using repetitive transcranial magnetic stimulation (rTMS), we assessed the role of V5/MT⁺ and V3⁺ in coherent motion processing. The hemianopes and four control subjects performed a two-interval forced-choice task in which they judged whether a pattern of coherently moving first-order or second-order textured squares moved in the first or second interval. They were not asked to report the direction of motion because neither of them could do so better than expected by chance. The results showed that MS, who has extensive destruction of the ventral cortical visual pathway as well as his V1 lesion, could not process second-order motion at all, whereas GY could perform second-order tasks but only at high-contrast modulation. This may have introduced first-order components in second-order moving stimuli and provided artifactual cues to motion. Moreover, rTMS delivered over area V5/MT⁺ impaired detection of both first- and second-order motion in undamaged control subjects, whereas rTMS over V3⁺ did not impair their performance in any of the stimuli employed. On the other hand, rTMS over V3⁺ did impair GY’s detection of first-order motion and high-contrast second-order moving textured squares that are likely to contain artifactual luminance cues. rTMS over V5/MT⁺ impaired first-order motion detection in MS. Overall, the results suggest that neither of the blindsight patients can detect artifact-free second-order motion.