恶性血液病患者313例染色体核型分析及临床意义

目的探讨血液系统疾病中白血病、骨髓增生异常综合征（MDS）、多发性骨髓瘤（MM）等恶性血液病的染色体核型变化特点与临床意义。方法回顾性分析2007年10月至2012年12月在该院门诊和住院的313例血液系统疾病患者的临床特征,包括细胞形态学、细胞遗传学核型及临床特征,分析染色体核型异常情况、核型特点及与疾病之间的关系。所有患者均在无菌条件下抽取骨髓标本2～5 mL,肝素抗凝,按细胞数（1～2）×10^6mL^-1加入到培养基RPMI1640组合培养液中,同时采用直接法和/或短期培养法制片,平均每例分析20～30个中期分裂细胞,以R显带技术进行染色体核型分析。结果本组313例恶性血液病患者中,染色体核型异常139例,总体检出率44.41%。139例患者中,异常克隆包括结构异常和数目异常。其中结构异常以特异性染色体重排t（8;21）,t（15;17）,t（9;22）多见,数目异常以＋8最为常见,其次有＋21、-X、-Y常见,-7/7q-,17p-,11号染色体异常也易见。与FAB亚型的关系中,88%的急性早幼粒细胞白血病（APL）有t（15;17）易位,50%急性粒细胞白血病微分化型（AML-M2）有t（8;21）易位,38%的急性淋巴细胞白血病（ALL）有t（9;22）易位,95%慢性粒细胞白血病（CML）有t（9;22）易位。1例MDS发现del（20）（q11;q13）,8例为单纯＋8异常,3例为单纯的-Y异常。结论大约50%的急性白血病（AL）存在克隆性染色体异常,一些特异性染色体改变是AL的细胞遗传学特征,与AL的FAB分型有明显相关性。染色体核型分析在血液系统疾病诊断、分型、预后判断和随访监测中有重要的临床价值。     

急性白血病患者的染色体核型分析及临床意义

目的结合细胞形态学、免疫学探讨染色体核型在急性白血病(AL)中的诊断、治疗价值。根据国内外细胞遗传学危险度划分标准,分析核型与完全缓解率(CR)的相关性。方法采用短期培养法处理骨髓样本,并以R显带为主,G显带为辅,对119例初诊的AL患者进行染色体核型分析,并观察患者CR与染色体核型分析之间的关系。结果患者核型率异常在急性髓细胞白血病(AML)、急性淋巴细胞白血病(ALL)中分别为58.11%、53.33%,平均异常率为56.30%,AML患者中最常见的平衡易位为46,XY,t(15;17)(q22;q21),占所分析患者的19.33%(23/119),且仅在M3中检测到,其次是t(8;21)(q22;q22),占10.08%(12/119)。在ALL患者中最常见的为t(9;22)(q34;q11),且多见于B-ALL,占6.72%。119例患者中首次化疗CR达71.43%,特异性染色体核型的患者CR较高。结论染色体检查技术结合细胞形态学、免疫表型分析对于白血病的准确诊断、靶向治疗、评估预后具有重要意义。     

伴有t(9;12)(q22;p13)易位的急性髓细胞白血病M2a

目的报告1例伴有t(9;12)(q22;p13)易位的急性髓细胞白血病M2a。方法患者骨髓细胞短期培养后按常规方法制备染色体,采用R显带技术进行染色体核型分析;以9号和12号整条染色体涂染探针对其进行染色体涂染检测。结果染色体核型和染色体涂染分析均证实该患者具有t(9;12)(q22;p13)克隆性染色体异常。结论t(9;12)(q22;p13)易位是急性髓细胞白血病M2a的一种新的临床遗传学类型。     

儿童急性淋巴细胞白血病的细胞遗传学检测

目的探讨儿童急性淋巴细胞白血病（ALL）中的细胞遗传学变化的特点。方法应用常规染色体显带技术及染色体核型分析方法对60例儿童ALL进行染色体核型分析检测骨髓白血病细胞的细胞遗传学变化。结果 60例儿童ALL通过染色体核型分析检出异常共26例（占43.3%）。结论儿童ALL容易出现细胞遗传学改变,常规染色体核型因各种原因导致检出率降低,应联合FISH检测异常克隆以提高检出率。     

5例Ph染色体阳性的急性白血病临床和实验室分析

目的了解Ph染色体阳性(Ph )急性白血病(AL)的临床特点及预后.方法对75例AL患者,采用骨髓细胞直接法或短期培养法制备染色体,经常规细胞遗传学检查确诊5例Ph 的AL,并对其进行荧光原位杂交研究,观察其临床特点、实验室改变和预后.结果 Ph AL占同期AL的6.7%.5例Ph 中急性淋巴细胞白血病4例,急性髓细胞白血病1例;3例为单纯t(9;22),bcr-abl融合基因均阳性;2例同时出现其它的染色体异常,其中1例为少见的继发性Ph ;4例外周血WBC>100×109/L.5例中3例获完全缓解,但又于半年内复发,5例均在1年内死亡,中位生存期为4.6个月.结论 Ph AL具有独特的临床、血液学和预后特点,是一种预后不良的细胞遗传学改变.     

细胞遗传学在急性早幼粒细胞白血病的诊断及预后评估中的作用

目的探讨细胞遗传学在急性早幼粒细胞白血病（APL）的诊断及预后评估中的应用价值。方法应用常规细胞遗传学分析APL初诊患者39例,采用R显带技术进行染色体核型分析。随访分析完全缓解率、复发率。结果39例APL患者中,染色体异常38例,其中30例为典型t（15;17）易位,8例为涉及15和17号染色体的复杂核型。形态学误诊为M2和M5各1例,经核型分析确诊。经全反式维甲酸和（或）化疗联合诱导治疗,37例获完全缓解,2例具有复杂核型者未取得完全缓解,6例具有复杂核型者第1次完全缓解后3年内复发,复发率86％（6／7）,其他核型组完全缓解后3年内复发率仅10％（3／31）。结论细胞遗传学对细胞形态不典型APL具有确诊价值,复杂染色体异常者预后不佳。     

恶性血液病183例染色体核型分析

目的探讨细胞染色体检查对恶性血液病的特点及临床意义。方法选择2006年8月至2011年5月初诊的恶性血液病患者183例,每例治疗前行骨髓涂片检查、骨髓活检、染色体核型分析。结果 183例患者中,有103例检出异常染色体核型。其中急性白血病40例,浆细胞白血病1例,淋巴瘤细胞白血病2例,慢性粒细胞白血病(CML)25例,骨髓增生异常综合征22例,多发性骨髓瘤组6例,骨髓增殖性疾病6例,再生障碍性贫血1例。与FAB亚型的关系中,75%M3有t(15;17)易位,M6有1号染色体异常,60%M2有t(8;21)易位,92%(CML)有t(9;22)易位。结论染色体核型分析是恶性血液病诊断分型的一项重要指标。     

慢性粒细胞白血病染色体核型分析及临床意义

目的:探讨细胞遗传学分析方法研究慢性粒细胞白血病(CML)染色体异常特征及其临床意义.方法:对70例骨髓或外周血细胞采用短期培养法(24～48小时)制备染色体,以G显带进行核型分析,并观察接受治疗后患者的临床转归.结果:70例CML患者中,66例检出典型Ph染色体(94.29%),6例伴有染色体数目异常(8.57%),其中6例出现复杂易位(8.57%),4例出现附加染色体异常(5.71%).染色体数目异常预后较差.结论:CML患者进行染色体分析对于疾病的诊断、临床治疗、判断预后具有重要意义.     

41例慢性髓细胞白血病细胞遗传学分析

目的探讨本地区慢性髓细胞白血病（CML）的细胞遗传学特点及临床意义。方法采用直接法和24h短期培养法制备骨髓染色体。应用R显带技术对41例CML患者的骨髓细胞进行染色体核型分析。结果41例CML中40例Ph（＋）,1例Ph（-）,40例Ph（＋）中具有典型易位即t（9;22）（q34;q11）30例;变异易位和涉及其他染色体异常的有11例,除＋8、＋21、i（17q）和2Ph国内常见报道外,t（11;9;22）、der（20）、t（1;17）等异常属少见。结论CML患者进行染色体核型分析对于疾病的诊断及鉴别、指导临床治疗、判断预后具有重要意义。     

探讨反复自然流产与染色体核型异常的关系

目的探讨和分析反复自然流产与夫妻双方染色体核型异常间的相互关系。方法 426对反复自然流产夫妇,对其采集静脉血,进行外周血淋巴细胞培养,使用常规的方法制备染色体标本,对染色体核型进行分析。结果 426对反复流产夫妇染色体中,共查出染色体异常的患者76例,所占比为8.92%(76/852),其中有9例为相互易位,5例为罗伯逊易位,3例为倒位,1例为重复,染色体多态性变异58例。结论反复自然流产与夫妻双方染色体核型异常之间有密切的关系,因此对于反复自然流产患者,应对其进行细胞遗传学检查诊断。     

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.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

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.