粒细胞集落刺激因子与感染

集落刺激因子是调节体内外造血干细胞及成熟白细胞功能的一组糖蛋白生长因子，而粒细胞集落刺激因子则是其中一种主要作用于中性粒细胞的集落刺激因子。本文阐述粒细胞集落刺激因子的产生与作用，对感染的反应性性即体内存在感染时其上升情况，以及对免疫缺隐患者的治疗等问题。     

粒细胞集落刺激因子及其受体

粒细胞集落刺激因子（Ｇ－ＣＳＦ）是一种多肽链的细胞生长因子,可特异地调节粒系细胞的增殖与分化,并能增强成熟粒细胞的功能,对机体应激防御系统有重要意义。近年来发现Ｇ－ＣＳＦ与白血病细胞的凋亡有一定关系。Ｇ－ＣＳＦ功能的发挥有赖于与效应细胞表面的特异性受体的结合。随着基因克隆技术的发展,Ｇ－ＣＳＦ重组产品已广泛用于临床,为血液病及其他疾病的治疗提供了有力的手段。１　Ｇ－ＣＳＦ的生物学作用人类Ｇ－ＣＳＦ由单个基因编码,其基因位于１７号染色体的ｑ２１－２２区,长约２．５ｋｂ,有５个外显子和４个内含子;其…     

粒细胞集落刺激因子治疗心肌梗死

粒细胞集落刺激因子治疗心肌梗死,能动员骨髓干细胞迁移至梗死部位,并分化为心肌细胞、平滑肌细胞、血管内皮细胞,从而减少梗死面积,改善心脏功能,但动物实验结果仍存在着矛盾,临床应用的有效性和安全性还需进一步探讨.     

结核性脑膜炎脑脊液细胞学的临床研究

目的 探讨脑脊液(cerebrospinal fluid,CSF)细胞学对结核性脑膜炎的诊断及预后评估价值。 方法 对766例结核性脑膜炎、103例化脓性脑膜炎、107例病毒性脑膜炎患者脑脊液分别应用细胞玻片离心沉淀器收集CSF细胞、采用迈-格-姬（May-Gruwald-Giemsa,MGG）染色法、光学显微镜分类计数,对CSF细胞进行动态观察。结果 766例结核性脑膜炎患者中700例CSF细胞学显示为混合细胞型,占91.38%（700/766）,66例显示为淋巴样细胞型,占8.62%（66/766）。103例化脓性脑膜炎患者以中性粒细胞型为主,107例病毒性脑膜炎患者以淋巴细胞型为主。大淋巴样细胞在结核性脑膜炎中的出现率为97.52%(747/766),而化脓性脑膜炎及病毒性脑膜炎则偶见,分别为9.71%（10/103）和14.02%（15/107）;结核性脑膜炎随着病情好转,中性粒细胞、大淋巴样细胞逐渐减少。化脓性脑膜炎随着抗炎治疗,中性粒细胞逐渐减少直至消失;病毒性脑膜炎中性粒细胞一般在24 h内消失。结论 CSF细胞学的类型及动态变化可以作为鉴别3种脑膜炎的依据之一,并对结核性脑膜炎患者的预后评估有参考作用。     

粒细胞集落刺激因子治疗粒细胞缺乏症疗效观察

1999～2003年，我院应用重组粒细胞集落刺激因子(rhG-CSF)治疗粒细胞缺乏症，疗效较好。现报告如下。     

粒细胞集落刺激因子与心血管疾病

近年来大量的研究表明骨髓干细胞能够促进心肌梗死后侧支循环的形成,加快血管损伤后内皮的修复.粒细胞集落刺激因子是一类血液生长因子,近来研究发现它可以动员骨髓干细胞,使它们归巢到梗死区域,复制、分化并促进心肌的修复.本文就粒细胞集落刺激因子在心血管疾病,包括心肌梗死、血管损伤后再狭窄和心力衰竭中的作用机制及应用进行综述.     

甲状腺功能亢进症患者外周血中粒细胞集落刺激因子及其受体表达的意义

目的:观察甲状腺功能亢进(简称甲亢)患者外周血中粒细胞集落刺激因子(G-CSF)和其受体(G-CS-FR)的表达及临床意义。方法:采用双抗体夹心ELISA法和G-CSFR单克隆抗体及流式细胞技术,检测63例初发甲亢患者、22例应用抗甲状腺药物(ATD)治疗控制的甲亢患者及43例正常人外周血中G-CSF和G-CSFR的表达水平,分析粒细胞计数与G-CSF水平及G-CSFR表达的关系。结果:G-CSFR表达率、白细胞总数及中性粒细胞绝对值三组间均无明显差异(P>0.05)。初发甲亢组和甲亢控制组血清G-CSF水平均明显高于正常对照组(P<0.01和P<0.05);各组中G-CSF和G-CSFR与白细胞计数之间无明显的相关性(P>0.05)。结论:甲亢患者外周血中G-CSF水平是升高的,可能与机体免疫反应有关。     

粒细胞集落刺激因子在急性心肌梗死治疗中的作用

急性心肌梗死是冠心病的一种严重类型，能够导致心肌细胞数量减少和心肌组织瘢痕形成，使心功能受损，发生心力衰竭，是目前心力衰竭的主要原因。近年来，许多研究发现粒细胞集落刺激因子（granulocyte—colony stimulating factor，G-CSF）具有促进心肌梗死后的组织修复和改善心功能的作用，为急性心肌梗死的治疗提供了又一新途径。国内外的动物实验和临床研究发现G-CSF可能通过多种机制影响心功能，现将其相关机制的研究综述如下。     

重组人粒细胞巨噬细胞集落刺激因子临床应用现况及前景

重组人粒细胞巨噬细胞集落刺激因子临床应用现况及前景林榕，楼方定ＪｏｎｅｓＴ．Ｃ１９９３年９月９～１１日在瑞士卢塞恩（Ｌｕｃｅｒｎｅ）召开了重组人粒细胞巨噬细胞集烙刺激因子（ｒｈＧＭ－ＣＳＦ，商品名ｌｅｕｃｏｍａｘ，生白能）的国际研讨会，来自美国、瑞士...     

Predictive Value of Serum and Cerebrospinal Fluid Procalcitonin Levels for the Diagnosis of Bacterial Meningitis

Background: The value of serum and cerebrospinal fluid (CSF) procalcitonin for differentiating between acute bacterial and viral meningitis was assessed and compared to other parameters which are usually used in clinical practice. Patients: 45 adult patients (20 with bacterial and 25 with tick-borne encephalitis, TBE) were included in this prospective study. Results: The median serum procalcitonin level in patients with bacterial meningitis was 6.45 ng/ml (range 0.25–43.76 ng/ml) and in the group with viral meningitis 0.27 ng/ml (range 0.05–0.44 ng/ml). 11 patients with bacterial meningitis had an elevated procalcitonin concentration not only in serum, but also in CSF. A serum procalcitonin level > 0.5 ng/ml had a positive predictive value for bacterial meningitis of 100% and a negative predictive value of 93%, while corresponding values for CSF procalcitonin were 100% and 74%, respectively. Conclusion: Serum and CSF procalcitonin concentrations > 0.5 ng/ml appear to be a reliable indicator of bacterial central nervous system (CNS) infection, with maximal positive predictive values and high negative predictive values. Received: October 23, 2000 · Revision accepted: June 1, 2001     

蛛网膜下腔出血患者脑脊液血小板活化因子的变化

目的 观察蛛网膜下腔邮血（ＳＡＨ）时血小板活化因子（ＰＡＦ）的变化及其临床意义。方法 用高铲薄层层析法对１６例ＳＡＨ患者发病第一、第二及第三周时脑脊液及发病后３天血浆中ＰＡＦ进行检测,并与１０例对照组进行比较。结果 蛛网膜下腔出血组与姐血浆ＰＡＦ一比较无显著性差异,对照组脑脊液ＰＡＦ均为阴性,而ＳＡＨ后第一周脑脊液中ＰＡＦ即呈阳性,第二周含量最高,第三周时有下降趋势,结论ＰＡＦ可能与ＳＡＨ患者脑血     

Stable Response after Administration of Stem Cell Factor Combined with Granulocyte Colony-Stimulating Factor in Aplastic Anemia

We report successful treatment with 25 microg/kg of recombinant methionyl human stem cell factor (SCF) combined with 400 microg/m2 of recombinant human granulocyte colony-stimulating factor (G-CSF) in 2 patients with aplastic anemia refractory to immunosuppressive therapy. In one patient, hemoglobin levels increased from 6.4 g/dL to 11.3 g/dL after 36 weeks of SCF/G-CSF treatment. Thereafter, the platelet count (24.0 x 10(9)/L) began to improve without the therapy, and as of week 272, the platelet count was 125.0 x 10(9)/L with a leukocyte count of 8.4 x 10(9)/L and a hemoglobin level of 12.9 g/dL. In the other patient, more than 3 years of SCF/G-CSF treatment ameliorated hemoglobin levels and platelet counts from 5.8 g/dL to 15.9 g/dL and 8.0 x 10(9)/L to 50.0 x 10(9)/L, respectively. After cessation of SCF/G-CSF treatment, the positive response was sustained, and the platelet count improved further to 71.0 x 10(9)/L as of week 242. These observations suggest the clinical benefit of SCF/G-CSF administration to patients with refractory aplastic anemia.     

Elevated Granulocyte Colony-Stimulating Factor, Non-Infectious Leukocytosis and Fevers in a Patient with Multiple Myeloma

Background: We report the case of a 56-year-old male with multiple myeloma in whom recurrent fevers and leukocytosis delayed potentially effective chemotherapy due to concern for active infection. Design and measurements: A thorough infectious workup, including CT and PET scans, was negative. The patient was eventually found to have an elevated serum granulocyte colony-stimulating factor (G-CSF) of 113 pg/ml (normal range 0.0 – 39.1 pg/ml), which was likely the cause of his persistent leukocytosis and fevers. Multiagent chemotherapy was initiated, and the fevers resolved in the next 4 days. Results: Leukocyte concentrations trended down after initiation of chemotherapy, but it is uncertain how much of the decline was attributable to immunosuppression. Conclusion: We report this well-documented case to demonstrate that G-CSF production should be considered as a cause of unexplained fever and leukocytosis in patients with multiple myeloma to prevent inappropriate and delayed definitive diagnosis and treatment.     

Evaluation of Cerebrospinal Fluid for the Presence of Anticardiolipin Antibodies (aCL) in NP-SLE Patients

Many neurological or psychiatric manifestations of SLE (NP-SLE) are related to the presence of anticardiolipin antibodies (aCL) in the patient’s sera. The aim of this study was to evaluate the presence of aCL in cerebrospinal fluid (CSF) in SLE patients with NP features. Fifteen SLE patients were studied, all with NP features. CSF was evaluated for intrathecal IgG synthesis, oligoclonal IgG, and blood–brain barrier impairment. Sera and CSF were tested by ELISA for the presence of aCL-IgG and aCL-IgM with and without β₂ glycoprotein (β₂ GPI) cofactor. CSF and sera of 50 low back pain patients served as controls. Six patients were aCL(+) and nine aCL(–). In all patients the general CSF examination was normal. In all patients the value of indices of intrathecal IgG synthesis were normal but oligoclonal protein was present in the CSF of three patients. In none of the patients was the blood–brain barrier impaired. Neither aCL-IgG nor aCL-IgM was detected in the CSF of any NP-SLE patient. Mean levels of aCL in patients without cofactor β₂ GPI and with cofactor were as follows: for IgG class 0.005 and 0.057 OD (negative); for IgM class 0.004 and 0.024 OD (negative). We could not detect aCL in the CSF of patients with NP-SLE, even if sera were positive for aCL. Received: 6 July 1999 / Accepted: 18 January 2000     

急性颅脑损伤后脑脊液中心钠素和精氨酸加压素含量变化及其临床意义

对３４例急性脑外伤患者脑脊液（ＣＳＦ）中心钠素（ＡＮＦ）和精氨酸加压素（ＡＶＰ）的含量进行放射免疫测定。结果表明脑外伤后４８小时和６～１０天ＣＳＦ中ＡＮＦ含量较对照组均明显降低（Ｐ＜０．００１）；ＡＶＰ含量较对照组明显升高（Ｐ＜０．００１）。伤后２～３周ＣＳＦ中ＡＮＦ水平升高，与对照组相比无明显差异（Ｐ＜０．０５）；ＡＶＰ水平降低，但仍明显高于对照组（Ｐ＜０．０１）。Ｇｌｏｓｇｏｗｃｏｍａｓｃａｌｅ（ＧＣＳ）≤８分者ＣＳＦ中ＡＶＰ含量高于ＧＣＳ＞８分者（Ｐ＜０．０５）；ＣＳＦ压力≥１．９６ｋＰａ者ＡＶＰ含量高于ＣＳＦ压力＜１．９６ｋＰａ者（Ｐ＜０．０５）。ＡＮＦ的含量变化与ＧＣＳ计分和ＣＳＦ压力无关，提示ＡＮＦ和ＡＶＰ可能参与颅脑损伤的病理生理变化，ＡＮＦ的分泌减少与ＡＶＰ的释放增加可能是导致脑外伤后继发脑水肿的重要因素。     

急性白血病患者脑脊液肿瘤坏死因子受体水平检测及其意义

目的 :探讨脑脊液中肿瘤坏死因子受体水平的检测对中枢神经系统白血病 (CNSL)的诊断、疗效评价及预后价值。方法 :采用双抗体夹心酶联免疫吸附法检测可溶性肿瘤坏死因子受体Ⅰ(sTNFRⅠ )和可溶性肿瘤坏死因子受体Ⅱ (sTNFRⅡ ) ,同时采用放射免疫法检测 β2 微球蛋白(β2 MG)作为参考 ,检测 5 5例急性白血病患者脑脊液 ,其中CNSL2 5例 ,并动态观察 6例CNSL鞘内化疗前后sTNFRⅠ、sTNFRⅡ和 β2 MG的变化 ,用logistic回归分析影响CNSL疗效的因素。结果 :CNSL组的sTNFRⅠ、sTNFRⅡ和 β2 MG明显高于无CNSL组 (P <0 .0 5 ) ,而无CNSL组与对照组比较 ,sTNFRⅠ、sTNFRⅡ和β2 MG未见显著性差异。动态观察发现 ,随着CNSL病情的好转 ,sTNFRⅠ、sTNFRⅡ和 β2 MG水平明显下降 ,CNSL的病情恶化 ,sTNFRⅠ、sTNFRⅡ和β2 MG水平也进一步上升。对可能影响CNSL患者疗效的 6种因素作了logistic回归分析 ,发现脑脊液中sTNFRⅠ水平对预测预后更具价值。结论 :脑脊液中sTNFR水平检测可作为诊断CNSL的一项指标 ,是疗效评价、预测预后的因素之一。     

Clincal, Cerebrospinal Fluid and Pathological Findings and Outcomes in HIV-Positive and HIV-Negative Patients with Tuberculous Meningitis

Background: The early diagnosis of tuberculous (TB) meningitis remains difficult. In South Africa, the HIV epidemic has shifted the spectrum of meningitis towards chronic infections (mainly tuberculosis [TB] and cryptococcosis). This study aimed to analyse clinical, cerebrospinal fluid (CSF) and pathological findings and outcomes in TB meningitis to evaluate whether HIV infection significantly influences the characteristic findings. Patients and Methods: 40 consecutive patients with TB meningitis presenting at the Pretoria Academic Hospital were evaluated clinically and chest-X-raxs (CXR), computerized tomography (CT) brain scans, CSF profiles, HIV and routine blood tests were analyzed. Postmortem examinations (PM) were performed in seen patients and outcomes were assessed after treatment. Results: 20 patients were HIV-positive and 17 were netgative (three not tested). History and clinical findings were similar in both groups. The mean Glasgow Coma Scale (GCS) value on admission was 13 in both groups, while CXR showed abnormalities consistent with TB in 9/17 with HIV and 7/15 without, with abnormal CT brain scans in 15/19 patients with HIV and 12/16 without. Dilated ventricles and infarcts occurred more commonly in HIV-positive patients. The CSF results showed similar results in both groups. PM in three HIV-positive patients showed weakly formed granulomas and extensive endarteritis and infarcts. Outcomes were similar in the two groups, but a low GCS value on admission was a better prognostic indicator thant the CD4-count in HIV-positive patients. Conclusion: HIV infection does not significantly alter clinical and CSF findings in TB meningitis in South Africa, but ventricular dilatation and infarcts are more frequent in HIV-positive patients. The GCS gives a better indicator of prognosis than the CD4-count. Received: November 10, 2000 · Revision accepted: June 2, 2001     

Combined corticosteroid/granulocyte colony-stimulating factor (G-CSF) therapy in the treatment of severe congenital neutropenia unresponsive to G-CSF: Activated glucocorticoid receptors synergize with G-CSF signals

More than 90% of patients with severe congenital neutropenia (SCN) respond to granulocyte colony-stimulating factor (G-CSF) therapy. The basis for the refractory state in the remaining patients is unknown. To address this issue, we studied a child with SCN who was totally unresponsive to G-CSF and had a novel point mutation in the extracellular domain of the G-CSF receptor (GCSF-R).Marrow stromal support of granulopoiesis was evaluated by plating CD34(+) cells on preformed stromal layers. Nonadherent cells were harvested and assayed in clonogenic assays for granulocytic colony production. The in vitro effect of G-CSF and corticosteroids on granulopoiesis was evaluated in clonogenic assays of marrow mononuclear cells, by proliferation studies of the murine myeloid cell line 32D expressing the patient's mutated G-CSFR, and by measuring STAT5 activation in nuclear extracts from stimulated cells.Patient's stroma supported granulopoiesis derived from control marrow CD34(+) cells in a normal manner. Normal stroma, however, failed to induce granulopoiesis from patient's CD34(+) cells. Clonogenic assays of the patient's marrow mononuclear cells incorporating either G-CSF or hydrocortisone produced little neutrophil growth. In contrast, inclusion of both G-CSF and hydrocortisone in the cytokine "cocktail" markedly increased the neutrophil numbers. Proliferation of 32D cells expressing the mutated receptor and STAT5 activation were improved by a combination of G-CSF and dexamethasone. When small daily doses of oral prednisone were then administered to the patient with conventional doses of subcutaneous G-CSF, the patient responded with increased neutrophil numbers and with a complete reversal of the infectious problems.These data provide insight into SCN unresponsive to standard G-CSF treatment and to the potential corrective action of combined treatment with G-CSF and corticosteroids through synergistic activation of STAT5.     

急性脑梗塞患者血清及脑脊液游离氨基酸递质水平的变化及临床意义

应用日立８３５－５０型氨基酸自动分析仪,对３０例发病１２小时至３天急性脑梗塞患者的血清氨基酸中兴奋在酸递质谷氨酸和天门冬氨酸水平明显升高;牛黄酸、甘氨酸递质水平下降,但差异不显著,血清中Ｇｌｕ和Ａｓｐ水平变化与脑梗塞直径呈显著正相关,与神经功能评分呈正相关。提示Ｇｌｕ和Ａｓｐ参与脑梗塞的病理过程,血清Ｇｌｕ和Ａｓｐ水平可作为临床观察其病情严重程度、梗塞面积的客观指标。