BACKGROUND & AIMS: :TNFalpha-induced expression of CD83 in leukocytes is mediated by NF-kappab. The aim of our present study was to investigate the underlying mechanism of a unique functional antagonism between GM-CSF and TNFalpha-induced up-regulation of CD83 in human neutrophils. CD83 was down-regulated by co-stimulation of neutrophils with TNFalpha and GM-CSF compared to TNFalpha alone both at the level of mRNA and protein. In marked contrast, the expression of IL-1RA was up-regulated under the same conditions. The down-regulation of CD83 was not mediated by modulation of the NF-kappab signaling pathway. Neither was it mediated by a decrease in mRNA stability of CD83. NF-kappab was modulated under these conditions as both the expression of the target gene IL-1RA as well as the phosphorylation of IkBalpha were up-regulated. Our results show that co-stimulation with pro-inflammatory cytokines such as TNFalpha and GM-CSF can have differential effects on inflammatory pathways initiated in the same target cell. GM-CSF can both synergize with TNFalpha in the case of expression of IL1-RA and antagonize in the case of CD83. Therefore, expression of CD83 as read out for activation of neutrophils in patients with inflammatory diseases is complicated by the presence of cross-modulating cytokines such as GM-CSF.

背景与目标： : TNFalpha诱导的白细胞中CD83的表达是由NF-κ b介导的。我们本研究的目的是研究gm-csf和TNFalpha诱导的人中性粒细胞CD83上调之间独特功能拮抗作用的潜在机制。与单独的TNFalpha相比，在mRNA和蛋白质水平上，通过与TNFalpha和gm-csf共同刺激中性粒细胞来下调CD83。明显相反，IL-1RA的表达在相同条件下上调。CD83的下调不是由NF-κ b信号通路的调节介导的。它也不是由cd83的mRNA稳定性降低介导的。在这些条件下调节NF-kappab，因为靶基因IL-1RA的表达以及IkBalpha的磷酸化均被上调。我们的结果表明，与促炎细胞因子 (例如TNFalpha和gm-csf) 的共刺激可以对同一靶细胞中启动的炎症途径产生不同的影响。Gm-csf既可以在IL1-RA表达的情况下与TNFalpha协同作用，又可以在cd83的情况下拮抗。因此，由于存在交叉调节细胞因子 (例如gm-csf)，因此在炎症性疾病患者中读取的CD83的表达为中性粒细胞的激活而变得复杂。

BACKGROUND & AIMS: :The choroid plexus (CP) is a highly vascularized structure located in the ventricles that forms the blood-CSF barrier (BCSFB) and separates the blood from the cerebrospinal fluid (CSF). In addition to its role as a physical barrier, the CP functions in CSF secretion, transport of nutrients into the central nervous system (CNS) and a gated point of entry of circulating immune cells into the CNS. Aging and neurodegeneration have been reported to affect CP morphology and function and increase protein leakage from blood to the CSF. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease associated with both upper and lower motor neuron loss, as well as altered proteomic and metabolomic signatures in the CSF. The role of the BCSFB and the CP in ALS is unknown. Here we describe a transcriptomic and ultrastructural analysis of BCSFB and CP alterations in human postmortem tissues from ALS and non-neurologic disease controls. ALS-CP exhibited widespread disruptions in tight junctional components of the CP epithelial layer and vascular integrity. In addition, we detected loss of pericytes around ALS blood vessels, accompanied by activation of platelet aggregation markers vWF and Fibrinogen, reminiscent of vascular injury. To investigate the immune component of ALS-CP, we conducted a comprehensive analysis of cytokines and chemokine panels in CP lysates and found a significant down-regulation of M-CSF and V-CAM1 in ALS, as well as up-regulation of VEGF-A protein. This phenotype was accompanied by an infiltration of MERTK positive macrophages into the parenchyma of the ALS-CP when compared to controls. Taken together, we demonstrate widespread structural and functional disruptions of the BCSFB in human ALS increasing our understanding of the disease pathology and identifying potential new targets for ALS therapeutic development.

背景与目标： : 脉络丛 (CP) 是位于心室中的高度血管化结构，形成血液CSF屏障 (BCSFB) 并将血液与脑脊液 (CSF) 分离。除了作为物理屏障的作用外，CP还在CSF分泌，营养物质向中枢神经系统 (CNS) 的运输以及循环免疫细胞进入CNS的门控点中起作用。据报道，衰老和神经变性会影响CP的形态和功能，并增加蛋白质从血液到CSF的泄漏。肌萎缩性侧索硬化症 (ALS) 是一种与上下运动神经元丢失以及CSF中蛋白质组和代谢组特征改变有关的神经退行性疾病。BCSFB和CP在ALS中的作用尚不清楚。在这里，我们描述了来自ALS和非神经系统疾病对照的人死后组织中BCSFB和CP改变的转录和超微结构分析。ALS-CP表现出CP上皮层紧密连接成分和血管完整性的广泛破坏。此外，我们检测到ALS血管周围周细胞的丢失，并伴有血小板聚集标志物vWF和纤维蛋白原的激活，使人联想到血管损伤。为了研究ALS-CP的免疫成分，我们对CP裂解物中的细胞因子和趋化因子进行了全面分析，发现ALS中m-csf和V-CAM1的显着下调以及vegf-a蛋白的上调。与对照组相比，这种表型伴随着MERTK阳性巨噬细胞浸润到ALS-CP的实质中。综上所述，我们证明了人类ALS中BCSFB的广泛结构和功能破坏，增加了我们对疾病病理的了解，并确定了ALS治疗发展的潜在新靶标。

BACKGROUND & AIMS: :Extensive survey of meiotic metaphase II arrest during oocyte maturation in vertebrates revealed that the mitogen-activated protein kinase (MAPK) pathway regulated by the c-mos proto-oncogene product, Mos, has an essential role in cytostatic activity, termed cytostatic factor (CSF). In contrast, little is known in invertebrates in which meiotic arrest occurs in most cases at metaphase I (MI arrest). A parthenogenetic insect, the sawfly Athalia rosae, in which artificial egg activation is practicable, has advantages to investigate the mechanisms of MI arrest. Both the MAPK/extracellular signal-regulated protein kinase kinase (MEK) and MAPK were phosphorylated and maintained active in MI-arrested sawfly eggs, whereas they were dephosphorylated soon after egg activation. Treatment of MI-arrested eggs with U0126, an inhibitor of MEK, resulted in dephosphorylation of MAPK and MI arrest was resumed. The sawfly c-mos gene orthologue encoding a serine/threonine kinase was cloned and analyzed. It was expressed in nurse cells in the ovaries. To examine CSF activity of the sawfly Mos, synthesized glutathione S-transferase (GST)-fusion sawfly Mos protein was injected into MI-resumed eggs in which MEK and MAPK were dephosphorylated. Both MEK and MAPK were phosphorylated again upon injection. In these GST-fusion sawfly Mos-injected eggs subsequent mitotic (syncytial) divisions were blocked and embryonic development was ceased. These results demonstrated that the MEK-MAPK pathway was involved in maintaining CSF arrest in sawfly eggs and Mos functioned as its upstream regulatory molecule.

背景与目标： : 对脊椎动物卵母细胞成熟过程中减数分裂中期II停滞的广泛调查表明，由c-mos原癌基因产物Mos调节的丝裂原活化蛋白激酶 (MAPK) 途径在细胞抑制活性中具有重要作用，称为细胞抑制因子 (CSF)。相反，在无脊椎动物中鲜为人知，在大多数情况下，减数分裂停滞发生在中期I (MI停滞)。一种孤雌生殖昆虫，锯蝇Athalia rosae，在人工卵激活中是可行的，具有研究MI阻滞机制的优势。MAPK/细胞外信号调节蛋白激酶 (MEK) 和MAPK在MI被捕的锯蝇卵中均被磷酸化并保持活性，而在卵激活后不久就被去磷酸化。用MEK抑制剂U0126处理MI停滞的卵，导致MAPK去磷酸化，并恢复MI停滞。克隆并分析了编码丝氨酸/苏氨酸激酶的sawfly c-mos基因直系同源物。它在卵巢的护士细胞中表达。为了检查锯蝇Mos的CSF活性，将合成的谷胱甘肽S-转移酶 (GST) 融合的锯蝇Mos蛋白注射到MI恢复的卵中，其中MEK和MAPK被去磷酸化。注射后，MEK和MAPK均再次磷酸化。在这些GST融合的sawfly Mos注入的卵中，随后的有丝分裂 (合胞体) 分裂被阻断，并且停止了胚胎发育。这些结果表明，mek-mapk途径参与维持锯蝇卵中CSF的停滞，而Mos充当其上游调节分子。

BACKGROUND & AIMS: BACKGROUND:The mechanism underlying disease progression in progressive multiple sclerosis (MS) is uncertain. Pathological studies found widespread inflammation in progressive MS brains correlating with disease progression and axonal damage. OBJECTIVES:To study cerebrospinal fluid (CSF) biomarkers and clarify whether inflammation and axonal damage are associated in progressive MS. METHODS:Using enzyme-linked immunosorbent assay (ELISA), we analysed CSF from 40 secondary progressive (SPMS), 21 primary progressive (PPMS), and 36 relapsing-remitting (RRMS) and 20 non-inflammatory neurological disease (NIND) patients. Twenty-two of the SPMS patients participated in an MBP8298 peptide clinical trial and had CSF follow-up after one year. RESULTS:Compared to NIND patients, inflammatory biomarkers osteopontin and matrix metalloproteinase-9 (MMP9) were increased in all MS patients while CXCL13 was increased in RRMS and SPMS patients. Biomarkers of axonal damage (NFL) and demyelination (MBP) were increased in all MS patients. In progressive MS patients CSF levels of osteopontin and CXCL13 correlated with NFL while osteopontin and MMP9 correlated with MBP. MBP8298 treatment did not affect the levels of the biomarkers after one year of treatment. All biomarkers were continuously increased after one year of follow-up except MBP, which decreased. CONCLUSION:CSF biomarkers of inflammation, axonal damage and demyelination are continuously increased in progressive MS patients and correlate. These findings parallel pathology studies, emphasise a relationship between inflammation, axonal damage and demyelination and support the use of CSF biomarkers in progressive MS clinical trials.

背景与目标：

BACKGROUND & AIMS: :Emergency granulopoiesis refers to the increased production of neutrophils in bone marrow and their release into circulation induced by severe infection. Several studies point to a critical role for G-CSF as the main mediator of emergency granulopoiesis. However, the consequences of G-CSF stimulation on the transcriptome of neutrophils and their precursors have not yet been investigated in humans. In this work, we examine the changes in mRNA expression induced by administration of G-CSF in vivo, as a model of emergency granulopoiesis in humans. Blood samples were collected from healthy individuals after 5 d of G-CSF administration. Neutrophil precursors were sorted into discrete stages of maturation by flow cytometry, and RNA was subjected to microarray analysis. mRNA levels were compared with previously published expression levels in corresponding populations of neutrophil precursors isolated from bone marrow of untreated, healthy individuals. One thousand one hundred and ten mRNAs were differentially expressed >2-fold throughout terminal granulopoiesis. Major changes were seen in pathways involved in apoptosis, cytokine signaling, and TLR pathways. In addition, G-CSF treatment reduced the levels of four of five measured granule proteins in mature neutrophils, including the proantibacterial protein hCAP-18, which was completely deficient in neutrophils from G-CSF-treated donors. These results indicate that multiple biological processes are altered to satisfy the increased demand for neutrophils during G-CSF-induced emergency granulopoiesis in humans.

背景与目标： : 紧急粒细胞生成是指严重感染引起的骨髓中性粒细胞生成增加并释放到循环中。多项研究指出，g-csf作为紧急粒细胞生成的主要介质的关键作用。然而，尚未在人类中研究g-csf刺激对嗜中性粒细胞及其前体转录组的影响。在这项工作中，我们检查了体内使用g-csf诱导的mRNA表达的变化，作为人类紧急粒细胞生成的模型。给予g-csf 5天后，从健康个体收集血液样本。通过流式细胞仪将中性粒细胞前体分为成熟的离散阶段，并对RNA进行微阵列分析。将mRNA水平与先前发表的从未经治疗的健康个体的骨髓中分离出的中性粒细胞前体的相应群体中的表达水平进行了比较。一千个110 mrna在整个末端粒化过程中差异表达> 2倍。在涉及凋亡，细胞因子信号传导和TLR途径的途径中观察到主要变化。此外，g-csf处理降低了成熟嗜中性粒细胞 (包括前抗菌蛋白hCAP-18) 中五种测量的颗粒蛋白中的四种的水平，后者在来自g-csf处理的供体的嗜中性粒细胞中完全缺乏。这些结果表明，在g-csf诱导的人类紧急粒细胞生成过程中，多种生物学过程发生了变化，以满足对嗜中性粒细胞的需求增加。

BACKGROUND & AIMS: :AMD3100, a competitive antagonist of CXCR-4, disrupts the binding of its ligand, stromal cell-derived factor-1 (SDF-1), and facilitates stem cell mobilisation in patients with haematological malignancies. This study investigated the differential kinetics of CXCR-4 and adhesion molecule expression and their impact on stem cell yield during mobilisation with granulocyte-colony stimulating factor (G-CSF) (days 1-4) followed by AMD3100 in 10 patients with multiple myeloma. A four-colour flow cytometry-based determination of CXCR-4, VLA-4, L-selectin, PECAM, LFA-1 and CD44 expression on CD34+ cells and measurement of SDF-1 concentration were performed at different time points. After G-CSF alone, CXCR-4 expression on patients' blood and marrow CD34+ cells was significantly lower than in the healthy controls (p < 0.001), but allowed no prediction of stem cell yield. Except in the single poorly mobilising patient, AMD3100 led to a further significant decrease of CXCR4 (p = 0.001), which inversely correlated with the CD34+ counts in the blood (p = 0.005). SDF-1 level in patients' marrow was positively correlated with CXCR-4 expression on CD34+ cells (p = 0.011). It is interesting to note that the expression of adhesion molecules remained unaffected by AMD3100 administration. Further studies will define the possible prognostic role of AMD3100 mediated changes in CXCR-4 expression for the prediction of stem cell yield attainable with this new mobilisation regimen.

背景与目标： : AMD3100，CXCR-4的竞争性拮抗剂，破坏其配体基质细胞衍生因子1 (SDF-1) 的结合，并促进血液系统恶性肿瘤患者的干细胞动员。这项研究调查了10例多发性骨髓瘤患者在使用粒细胞集落刺激因子 (g-csf) 动员 (第1-4天) 和AMD3100动员期间CXCR-4和粘附分子表达的差异动力学及其对干细胞产量的影响。在不同时间点进行基于四色流式细胞仪的CD34细胞上CXCR-4，VLA-4，L-选择素，PECAM，LFA-1和CD44表达的测定以及SDF-1浓度的测量。单独使用g-csf后，患者血液和骨髓CD34细胞上的CXCR-4表达显着低于健康对照组 (p <0.001)，但无法预测干细胞产量。除了单个动员不良的患者外，AMD3100导致CXCR4进一步显着降低 (p = 0.001)，这与血液中的CD34计数成反比 (p = 0.005)。患者骨髓SDF-1水平与CD34 + 细胞CXCR-4表达呈正相关 (p = 0.011)。有趣的是，粘附分子的表达不受AMD3100给药的影响。进一步的研究将确定AMD3100介导的CXCR-4表达变化对于预测这种新的动员方案可获得的干细胞产量的可能的预后作用。

BACKGROUND & AIMS: :In most patients with superficial siderosis of the CNS, the exact source of bleeding remains unknown because of a lack of objective surgical data. The authors herein describe the case of a 58-year-old man with superficial siderosis of the CNS. The patient also had spinal CSF leakage due to a spinal dural defect. Repair surgery for the dural defect was performed using posterior laminoplasty with a transdural approach without spinal fixation. During repair surgery, the bleeding source was found to be the epidural vein around the defect. The intraoperative and histological results of the present case suggest that epidural veins exposed to CSF represent a chronic bleeding source in patients with superficial siderosis of the CNS complicated by CSF leakage. Dural repair surgery may result in discontinuation of the CSF leaks, resolution of the epidural CSF collection, and cessation of chronic epidural bleeding.

背景与目标： 在大多数中枢神经系统浅表铁皮病患者中，由于缺乏客观的手术资料，出血的确切来源仍然未知。本文的作者描述了一名58岁的患有中枢神经系统浅表铁皮病的男子的情况。该患者还因硬脊膜缺损而出现脊髓CSF渗漏。硬脑膜缺损的修复手术是使用后路椎板成形术和经硬脑膜入路而不进行脊柱固定的。在修复手术中，发现出血源是缺损周围的硬膜外静脉。本病例的术中和组织学结果表明，暴露于CSF的硬膜外静脉代表了中枢神经系统浅表铁皮沉着症并伴有CSF渗漏的患者的慢性出血源。硬脑膜修复手术可能导致CSF泄漏的中断，硬膜外CSF收集的消退以及慢性硬膜外出血的停止。

BACKGROUND & AIMS: :alpha 2-Macroglobulin (AMG) and C-reactive protein (CRP) levels in cerebrospinal fluid (CSF) of patients with bacterial and aseptic meningitis have been analyzed by a rate nephelometric method to determine if these acute phase proteins can aid in differentiation of bacterial from aseptic meningitis. The mean CSF concentrations of AMG and CRP were 15 and 3.5 times greater, respectively, in the bacterial compared to the aseptic meningitis group. Also, the range of AMG levels showed minimal overlap between the two groups. The elevated levels of the proteins persisted after CSF cultures became negative. Quantitation of specific acute phase proteins in CSF may assist the differentiation of bacterial from aseptic meningitis.

背景与目标： : 已通过速率浊度法分析了细菌性和无菌性脑膜炎患者脑脊液 (CSF) 中的 α2-巨球蛋白 (AMG) 和C反应蛋白 (CRP) 水平，以确定这些急性期蛋白是否可以帮助区分细菌和无菌性脑膜炎。与无菌性脑膜炎组相比，细菌中AMG和CRP的平均CSF浓度分别高15倍和3.5倍。此外，AMG水平的范围显示两组之间的重叠最小。CSF培养为阴性后，蛋白质水平持续升高。脑脊液中特定急性期蛋白的定量可能有助于细菌与无菌性脑膜炎的区分。

BACKGROUND & AIMS: :Glutamate is the principal excitatory neurotransmitter in the central nervous system, and is thought to be involved in the process of memory encoding and storage. Glutamate disturbances have also been reported in psychiatric disorders, such as schizophrenia and major depressive disorder (MDD), and in Alzheimer's disease. In this paper, we set out to study the relationship between cerebrospinal fluid (CSF) glutamate levels and memory performance, which we believe has not been reported previously. In particular, we focused on recall performance broken down by serial position. Our prediction was that the recency ratio (Rr), a novel cognitive marker of intellectual impairment, would be linked with CSF glutamate levels. We studied data from a group of cognitively intact elderly individuals, 28 of whom had MDD, while 19 were controls. Study results indicated that Rr levels, but no other memory score, were inversely correlated with CSF glutamate levels, although this was found only in individuals with late-life MDD. For comparison, glutamine or GABA were not correlated with any memory performance measure.

背景与目标： 谷氨酸是中枢神经系统中主要的兴奋性神经递质，被认为参与记忆的编码和存储过程。在精神疾病 (例如精神分裂症和重度抑郁症 (MDD)) 以及阿尔茨海默氏病中也有谷氨酸紊乱的报道。在本文中，我们着手研究脑脊液 (CSF) 谷氨酸水平与记忆性能之间的关系，我们认为以前没有报道过。特别是，我们专注于按序列位置细分的召回性能。我们的预测是，新近比 (Rr) 是一种新的智力障碍认知指标，将与CSF谷氨酸水平有关。我们研究了一组认知完整的老年人的数据，其中28例患有MDD，而19例为对照组。研究结果表明，Rr水平 (但没有其他记忆评分) 与CSF谷氨酸水平成反比，尽管这仅在晚期MDD患者中发现。为了进行比较，谷氨酰胺或GABA与任何记忆性能指标均不相关。

BACKGROUND & AIMS: Serum levels of GM-CSF, IL-3 and IL-6 were measured in patients with immune thrombocytopenia (ITP), non-immune thrombocytopenia (NIT), autoimmune haemolytic anaemia (AIHA) and neutropenia. 8/10 children with ITP had elevated serum levels of GM-CSF (mean 18.4 pg/ml) while thrombocytopenic, but only two had detectable levels (mean 4.5 pg/ml) after normalization of the platelet count. In patients with NIT a significant inverse correlation between platelet count and serum levels of GM-CSF was observed. IL-3 and IL-6 levels were not significantly elevated in thrombocytopenic patients and only two of the nine patients with either AIHA or neutropenia had detectable levels of GM-CSF. Thus, GM-CSF may play a role in the response of severe thrombocytopenia.

背景与目标： 检测免疫性血小板减少症 (ITP)，非免疫性血小板减少症 (NIT)，自身免疫性溶血性贫血 (AIHA) 和中性粒细胞减少症患者的血清gm-csf，IL-3和IL-6水平。8/10名患有ITP的儿童在血小板减少症时血清gm-csf水平升高 (平均18.4 pg/ml)，但在血小板计数正常化后，只有两个儿童的可检测水平 (平均4.5 pg/ml)。在NIT患者中，观察到血小板计数与血清gm-csf水平之间的显着负相关。血小板减少症患者的IL-3和IL-6水平没有显着升高，并且在9例AIHA或中性粒细胞减少症患者中只有2例可检测到gm-csf水平。因此，gm-csf可能在严重血小板减少症的反应中起作用。

BACKGROUND & AIMS: :Granulocyte-macrophage colony-stimulating factor (GM-CSF) is one of the four major colony-stimulating factors (CSFs) that regulate hematopoiesis. GM-CSF can stimulate a single bone marrow stem cell to proliferate and differentiate into mature neutrophils, eosinophils, granulocytes or macrophages. The outcome of recent clinical trials indicates that GM-CSF has the prospect of being clinically effective in augmenting the recovery of hematopoiesis in recipients of autologous bone marrow transplantation, in cancer patients suffering from the hematopoietic toxicity associated with chemotherapy and radiation therapy, and in patients with acquired immunodeficiency syndrome (AIDS).

背景与目标： 粒细胞巨噬细胞集落刺激因子 (gm-csf) 是调节造血的四大集落刺激因子 (CSF) 之一。Gm-csf可以刺激单个骨髓干细胞增殖并分化为成熟的中性粒细胞，嗜酸性粒细胞，粒细胞或巨噬细胞。最近的临床试验结果表明，gm-csf有望在临床上有效地增强自体骨髓移植接受者，患有化学疗法和放射疗法相关造血毒性的癌症患者以及患者的造血功能恢复获得性免疫缺陷综合症 (AIDS)。

BACKGROUND & AIMS: Colony-forming cells (CFC) and long-term culture-initiating cells (LTC-IC) include a spectrum of progenitor types whose potential contributions to the haemopoietic recovery seen in patients transplanted with mobilized peripheral blood progenitor cells (PBPC) remains unclear. We evaluated both the number and cycling status of the circulating LTC-IC and CFC harvested from 12 patients treated with chemotherapy and G-CSF using a modified 6-week LTC-IC assay. The frequency of the LTC-IC and CFC in the mobilized PB samples were increased 45- and 750-fold, respectively. Interestingly, comparison of these values for PB samples, taken just prior to the start of the leukapheresis, with the progenitor content of the 3 h harvest, showed that, on average, the leukapheresis product contained 19 times more LTC-IC (P < 0.01) than had been detectable in the entire blood volume of the patients at the start of the collection, whereas the number of CFC collected was approximately the same as the number in the initial circulating pool of PBPC. Cycling studies showed many of the LTC-IC in the apheresis collections to be proliferating although not more so than in the steady-state marrow LTC-IC compartment (i.e. per cent kill of mobilized LTC-IC after 16 h in 3H-Tdr = 70 +/- 8%, n = 9). On the other hand, the majority of the CFC in the apheresis collections were initially quiescent (per cent kill after 16 h in 3H-Tdr = 37 +/- 6%, n = 12). These findings demonstrate the rapidity with which a primitive subset of LTC-IC may enter the circulation during the early phase of rebound haemopoiesis induced by chemotherapy plus G-CSF and provide evidence of differences in the mechanisms regulating LTC-IC and CFC mobilization.

背景与目标： 集落形成细胞 (CFC) 和长期培养起始细胞 (LTC-IC) 包括一系列祖细胞类型，其对移植有动员的外周血祖细胞 (PBPC) 的患者的造血恢复的潜在贡献尚不清楚。我们使用改良的6周LTC测定法评估了从接受化学疗法和g-csf治疗的12例患者中收集的循环LTC-IC和CFC的数量和循环状态。动员的PB样品中LTC-IC和CFC的频率分别增加了45倍和750倍。有趣的是，将白细胞分离术开始之前的PB样品的这些值与3小时收获的祖细胞含量进行比较，结果表明，平均而言，白细胞分离产物含有的LTC-IC (P < 0.01) 比在收集开始时在患者的全部血容量中检测到的LTC多19倍，而收集的CFC的数量与PBPC的初始循环池中的数量大致相同。循环研究表明，单采收集中的许多LTC-IC正在增殖，尽管并不比稳态骨髓LTC-IC区室中的增殖更多 (即在3H-Tdr = 70 +/- 8% 中，16小时后动员的LTC-IC的杀死率，n = 9)。另一方面，单采收集中的大多数CFC最初是静止的 (在3H-Tdr = 37/- 6%，n = 12中，在16小时后杀死 %)。这些发现证明了LTC-IC的原始子集在化疗加g-csf诱导的反弹造血的早期阶段可能进入循环的速度，并提供了调节LTC-IC和CFC动员机制差异的证据。

BACKGROUND & AIMS: AIM:To carry out a prospective, multicenter and observational study describing prophylactic strategies [cycle delay, dose-reduction, (G-CSF) prescription] to prevent recurrence of neutropenic events (NE) in patients with solid tumors, and identify potential predictive factors of NE recurrence. PATIENTS AND METHODS:Patients ≥18 years old with an NE in a previous chemotherapy cycle (cycle A) without G-CSF support, followed for four cycles (B to E) were included in the study. NE was defined as any neutropenia grade 1-4, febrile or not, which impacted on subsequent chemotherapy cycles (cycle delay, or reduction, or prophylactic G-CSF). RESULTS:Data of 548 patients were analyzed, 378 (69%) were female, with a mean (SD) age of 61.7 (12.3) years. WHO PS: 0-1: 88.3%, incidence of breast cancer: 40%, metastatic disease: 53.3%. Following the first NE episode, 44.5% of patients had cycle delay, 22.3% dose reduction and 466 (85%) received prophylactic G-CSF. NE recurrence rates were: 21.2% at cycle B, 18.6% at cycle C, 11.5% at cycle D and 12.9% at cycle E. G-CSF support (hazard ratio: 0.32, 0.24-0.43, p<0.001) was associated with lower NE recurrence. Pegfilgrastim seemed to offer the highest protection (hazard ratio; HR=0.23, 95% CI: 0.16-0.32; p<0.001). CONCLUSION:Secondary G-CSF prophylaxis has significant efficacy in reducing the incidence of NE and should be considered as a valuable option.

背景与目标：

BACKGROUND & AIMS: :Serum and CSF calcium, magnesium, potassium and sodium were analyzed in 14 patients suffering from subarachnoid haemorrhage and in 10 healthy controls. The calcium and potassium concentrations in serum and CSF were decreased while magnesium unchanged and sodium were unchanged. A deranged electrolyte homeostasis was thus detectable in the CSF following subarachnoid haemorrhage. It could not be established whether symptoms of delayed cerebral ischemia were related to CSF calcium and/or potassium levels.

背景与目标： : 对14例蛛网膜下腔出血患者和10例健康对照者的血清和CSF钙，镁，钾和钠进行了分析。血清和CSF中的钙和钾浓度降低，而镁不变，钠不变。因此，蛛网膜下腔出血后，在CSF中可以检测到紊乱的电解质稳态。无法确定迟发性脑缺血的症状是否与CSF钙和/或钾水平有关。

BACKGROUND & AIMS: :Despite their names, the cytokines granulocyte- and granulocyte-macrophage-colony stimulating factor (G-CSF and GM-CSF respectively) have actions far beyond simply stimulating the proliferation of neutrophil and monocyte lineage cells. A comprehensive body of evidence now exists demonstrating that G-CSF and GM-CSF effectively mobilize bone-marrow-derived progenitor cells into the peripheral circulation. These mobilized progenitor cells can be conveniently harvested for use in reconstituting bone marrow by transplantation after myelo-ablative treatment of hematological malignancies. In addition, much evidence has recently emerged to suggest that these cytokines may have multiple direct and indirect beneficial cardiovascular effects--including neovascularization of ischemic myocardium and reducing the extent of myocardial damage after infarction. Based on this knowledge and a strong safety record in hematological applications, a number of early clinical trials have evaluated the use of G-CSF or GM-CSF in patients with both acute and chronic myocardial ischemia. Although the interpretation of these trials is complicated by heterogeneity in study design, small patient numbers and methodological concerns related to appropriate selection and blinding of patients, the results of ongoing larger phase II/III trials should soon be available to determine if these agents will be useful additions to the cardiovascular armamentarium.

背景与目标： : 尽管它们的名字，细胞因子粒细胞和粒细胞巨噬细胞集落刺激因子 (分别为g-csf和gm-csf) 的作用远远超出了简单地刺激中性粒细胞和单核细胞谱系细胞的增殖。目前存在大量证据，表明g-csf和gm-csf有效地将骨髓来源的祖细胞动员到外周循环中。这些动员的祖细胞可以方便地收集，用于在骨髓消融治疗血液系统恶性肿瘤后通过移植重建骨髓。此外，最近出现了许多证据，表明这些细胞因子可能具有多种直接和间接的有益心血管作用-包括缺血心肌的新血管形成和减少梗塞后心肌损伤的程度。基于这些知识和血液学应用中的强大安全性记录，许多早期临床试验已经评估了g-csf或gm-csf在急性和慢性心肌缺血患者中的使用。尽管这些试验的解释因研究设计的异质性，患者人数少以及与患者的适当选择和盲法相关的方法学问题而变得复杂，但正在进行的大型II/III期试验的结果应很快可用，以确定这些药物是否将成为心血管武器库的有用补充。