中心体Plk1在儿童急性白血病中的表达及其意义

目的 研究Polo-like kinase 1(Plk 1)在儿童急性白血病骨髓细胞中的表达水平.方法 采用免疫组化法检测Plk 1在儿童急性白血病骨髓细胞中的表达水平.结果 30例急性非淋巴细胞白血病(acute non-lymphoblastic Ieukemia,ANLL)及30例急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)儿童患者与19例正常儿童(normal,N)骨髓细胞比较,Plk 1表达有显著性差异(X=43.947,P<0.01),在ANLL及ALL中表达水平明显高于正常儿童.结论 Plk1在儿童急性白血病中呈异常高表达,可能成为白血病治疗的有效靶点及重要标志物.     

急性髓系白血病中CD117的表达与临床意义

目的探讨CD117的表达在急性白血病诊断中的价值。方法利用流式细胞仪检测了51例急性髓细胞性白血病、30例急性淋巴性白血病和20例正常骨髓细胞CD117的表达,并比较了CD117在AML、ALL和正常人间的表达差异。结果 CD117在正常人表达为阴性,在AML患者中高表达(43/51),但很少在ALL中表达(1/30),两者比较差异有统计学意义(x2=49.9208,P=0.0000<0.0167)。结论 CD117的表达有助于AML的诊断。     

急性白血病中MLL基因重排研究进展

MLL基因位于11号染色体长臂2区3带(11q23),是HOX基因转录的上游调节因子。研究显示,恶性血液病及拓扑异构酶Ⅱ抑制剂诱导均可导致MLL基因重排[3-4]。在急性白血病中常见MLL基因重排,其甚至作为急性白血病的标志之一。MLL重排阳性多见于急性髓细胞白血病(acute myeloblastic leukemia,AML)、急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)、骨髓增生异常综合征(myelodysplastic syndrome,MDS)及治疗相关性白血病。MLL基因重排在儿童AML中占14%,其中65%与婴儿AML相关;该重排基因在ALL中发病占6%,其中大约80%为婴儿(<1岁)ALL患者;该重排基因也常在MDS及经拓扑异构酶     

靶向干预SETDB1对急性髓系白血病的治疗作用

目的 探究组蛋白甲基转移酶SETDB1在急性髓系白血病(acute myeloid leukemia,AML)恶性进展中的作用及干扰SETDB1对AML的治疗效果。方法 基于TCGA、GTEx、TARGET数据库,分析SETDB1在不同肿瘤的表达情况,并对比分析在AML骨髓细胞和正常骨髓细胞中的表达情况,进一步分析SETDB1的表达与AML患者不同风险分层、不同FAB(French-American-British)分型及微小残留病灶(minimalresidualdisease,MRD)的相关性;对SETDB1高/低表达患者进行基因富集分析。通过RT-qPCR考察shRNA序列对SETDB1的沉默效率;通过台盼蓝染色法考察沉默SETDB1对AML细胞的增殖及活力的影响;通过检测细胞表面抗原CD11b、CD14的比例、细胞核形态和氯化硝基四氮唑蓝(NBT)还原能力考察沉默SETDB1对AML细胞的分化治疗作用。结果 与其他肿瘤相比,SETDB1在AML中显著高表达,且在AML中的表达水平显著高于正常骨髓细胞。SETDB1在AML高风险患者中、MRD残留患者中也显著高表达。沉默SETDB...     

急性白血病患者血清中白细胞介素-21的表达及其意义

目的探讨白细胞介素-21在急性白血病患者血清中的表达情况及其意义。方法选择符合标准的65例白血病患者,根据疾病发生情况分成急性淋巴细胞性白血病(ALL)组(31例)与急性髓性细胞白血病(AML)组(34例),测定常规化疗前后患者血清IL-21水平。结果 ALL组与AML组血清IL-21水平均显著高于健康组(P0.05),且ALL组显著高于AML组(P0.05)。ALL组女性患者血清IL-21值均显著性高于ALL组男性患者与AML女性患者(P0.05)。在ALL组与AML组中,IL-21R阳性患者于IL-21R阴性患者在WBC与外周血幼稚细胞水平上存在显著性差异(P0.05)。结论通过检测患者血清中的IL-21水平能够用于辅助诊断急性白血病,同时区分ALL与AML,具有一定的临床价值,值得临床进行推广并进一步深入研究。     

氯法拉滨在儿童白血病治疗中的应用

目前儿童急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)5年无事件生存率(event-free survival,EFS)达70%以上,急性髓系白血病(acute myeloid leukemia,AML)5年EFS只有40%～50%,对于大约20%的难治性或复发性白血病患者,无论采用大剂量化疗还是造血干细胞移植,疗效都不理想,所以开发新     

急性白血病患者淋巴细胞PIM-2蛋白的表达

目的观察急性白血病患者淋巴细胞PIM-2蛋白的表达。方法将65例急性白血病患者作为观察组,另选同期健康体检者12例作为对照组。观察组急性髓系白血病(AML)患者41例,达到完全缓解(CR)者25例;急性淋巴系白血病(ALL)患者24例,达CR者14例。免疫印迹法检测2组淋巴细胞的PIM-2蛋白相对表达量。结果观察组ALL及AML患者各期PIM-2蛋白相对表达量均高于对照组,差异有统计学意义(P<0.05或P<0.01);观察组ALL及AML患者急性期PIM-2蛋白相对表达量均高于CR期,差异均有统计学意义(P<0.01);ALL及AML患者各期PIM-2蛋白相对表达量差异无统计学意义(P>0.05)。结论急性白血病患者的淋巴细胞PIM-2蛋白的表达量明显上调,急性期ALL与AML患者PIM-2蛋白的表达量明显高于CR期。PIM-2蛋白表达上调可能在急性白血病的发生发展中起着重要促进作用。     

定量检测WT-1基因在急性髓细胞白血病的表达水平及其临床意义

目的 通过采用反转录-聚合酶链式反应(RT-PCR)方法检测急性髓细胞白血病(AML)患者WT-1基因的表达情况,分析其表达水平与AML患者亚型关系,及其在AML临床疗效的作用.方法 采用实时荧光定量PCR方法分别检测10例正常人及48例初诊急性髓细胞白血病患者骨髓细胞WT-1基因mRNA的表达水平(拷贝数),将ABL基因作为内参照基因,比较AML组与对照组WT-1基因表达水平的差异性,以WT-1基因表达水平的中位数作为界值,将48例初诊AML分为WT-1基因高表达组和低表达组,并通过高表达组和低表达组间CR1率(初次诱导化疗缓解率)的差异,从而分析WT-1基因表达水平与急性髓细胞白血病预后的关系.结果 对照组WT-1基因表达水平中位数为0.008(0～0.019),AML组WT-1基因表达水平中位数为0.679(0～1.680),WT-1基因在AML骨髓细胞表达水平高于对照组,差异有统计学意义(P＜0.001).WT-1表达对AML患者治疗效果的影响:AML各亚型高表达组与低表达组初次诱导后完全缓解率(CR1率)差异有统计学意义(P＜0.05),WT-1高表达组缓解率低于低表达组,AML患者WT-1基因高表达组疗效比低表达组疗效差.结论 WT-1基因可作为AML微小残留病(MRD)的分子标志,也可作为AML预后分层的分子学指标.     

59例成人急性白血病流式细胞仪免疫表型结果分析

目的:探讨流式细胞仪免疫表型在急性白血病(AL)中的抗原表达规律及临床价值。方法:利用流式细胞仪进行四色免疫荧光标记术检测细胞免疫表型、骨髓细胞形态学分型对59例AL进行分析。结果:43例急性髓系白血病(AML)患者主要表达CD33,HLA-DR,CD13,MPO和CD117抗原,其中MPO和CD117抗原特异性高,同时还有18.64%的患者伴有淋系抗原(Ly+AML)CD7的表达,有10.16%的患者伴有淋系抗原(Ly+AML)CD19的表达;12例急性淋巴细胞白血病(ALL)患者主要表达CD79a,HLA-DR,CD19,CD20和CD10抗原,其中CD79a特异性和敏感性较高,同时有8.47%的ALL患者同时伴有髓系抗原CD13的表达;AML-M3多为CD34低表达,HLA-DR阴性;有4例形态学不能准确分型,需结合免疫表型分析才能确诊。结论:免疫分型与FAB同时结合互相补充,可提高AL的诊断分型准确率,有利于成人AL的诊断、治疗及预后判断,并能够确诊一些特殊类型的白血病。     

白血病抑制因子基因在急性白血病患者中的表达及意义

目的 研究急性白血病(acute leukemia,AL)患者外周血白血病抑制因子(leukemia inhibitory factor,LIF)mRNA的表达水平及其与AL病情、疗效和预后的关系.方法 采用逆转录聚合酶链反应(RT PCR)检测37例不同类型以及同一类型不同阶段AL患者[初治患者16例(初治亚组)、完全缓解患者12例(完全缓解亚组)、复发患者9例(复发亚组)]LIF的mRNA的表达水平,并与20例健康者(对照组)比较.结果 初治亚组LIF基因mRNA阳性表达率低于对照组和完全缓解亚组(P<0.05);复发亚组LIF基因mRNA阳性表达率低于完全缓解组(P<0.05);复发亚组与初治亚组比较及完全缓解亚组与对照组比较,LIF基因mRNA阳性表达率差异无统计学意义(P>0.05);LIF基因表达率在急性髓系白血病(AML)和急性淋巴细胞白血病(ALL)患者间无显著性差异(P>0.05).结论 LIF基因表达水平与AL患者病情变化密切相关.检测AL患者LIF基因表达情况,为AL患者检测病情、疗效评价、指导临床用药和预后判断,提供了一定的理论依据.     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.