应用组织芯片技术检测淋巴瘤患者EB病毒表达及意义

目的 探讨福建地区淋巴瘤与EB病毒(EBV)感染的关系.方法 应用组织芯片结合原位杂交技术检测121例淋巴瘤患者EB病毒的表达.结果 霍奇金淋巴瘤(HL)EBER(epstein-barr virus early RNA,EBER)阳性者均为经典型HL,检出率为52.2%(24/46);HL各型中检出率以LD型最高,3例均为阳性,MC型检出率83.3%(15/18),NS型和LP型分别为35.7%(5/14)和14.3%(1/7);非霍奇金淋巴瘤(NHL)中T细胞淋巴瘤检出率40.0%(20/50),其中鼻型结外NK/TCL检出率高达100%(9/9),结内、结外T细胞淋巴瘤检出率分别为18.2%(6/33)、82.4%(14/17),两组之间EBV感染率有明显差异(P<0.01).结论 福建地区淋巴瘤的发病与EB病毒的感染有一定的关系,其中以HL中MC和LD及NHL中的T-NHL与EB病毒的关系较为密切.而且T细胞淋巴瘤EBV感染有部位和类型倾向性的特点.     

非霍奇金淋巴瘤病毒病因学探讨

目的 探讨EBV、HCV与贵州地区NHL的相关性.方法 ISH方法检测180例NHL中EB病毒编码的小核苷酸EBER 1/2,采用原位RT-PCR法检测58例NHL中HCVRNA.IHC方法检测EBV潜伏膜蛋白LMP-1.结果 EBV感染率为42.8%(77/180),感染率依次为TCL64.8%、NK/T46.2%、BCL9.5%,TCL、NK/T与BCL相比,P＜0.005,面中线NHL感染率为72.4%,多形细胞性淋巴瘤感染率为70.1%.HCV感染率为18.97%(11/58),其中BCL占90.9%,消化道发生的BCL占63.6%,滤泡中心细胞来源淋巴瘤占54.5%.结论 EBV感染与本地区NHL关系密切,主要感染TCL和NK/T.HCV感染与本地区NHL有相关性,主要感染BCL.两种病毒感染均有部位限制性和类型倾向性.     

鼻炎 鼻息肉与鼻腔NK/T细胞淋巴瘤的关系

目的分析鼻炎、鼻息肉与鼻腔NK/T细胞淋巴瘤的关系。方法对郑州大学第一附属医院2007年1月至2011年7月收治病理学检查确诊的59例鼻腔NK/T细胞淋巴瘤患者的临床资料进行回顾及分析。结果 59例鼻腔NK/T细胞淋巴瘤患者均有鼻炎、鼻息肉病史,所有患者均有EB病毒(EBV)感染或感染史,50例(84.75%)患者诊断鼻炎时间大于1年,23例(38.98%)大于5年。21例(35.59%)患者诊断鼻息肉时间大于1年,2例(3.39%)大于5年。结论 NK/T细胞淋巴瘤与鼻炎、鼻息肉密切相关。     

早期NK/T细胞淋巴瘤79例患者的治疗结果和预后因素回顾性分析

<正>NK/T细胞淋巴瘤属于结外非霍奇金淋巴瘤(NHL)的一种少见类型,占NHL的5%¹5%。其发病可能与CD56表达及EB病毒感染相关的分子机制有关[1],具体机制尚不明确。由于NK/T细胞淋巴瘤多原发于鼻腔,因此称鼻腔NK/T细胞淋巴瘤,而原发于鼻以外(鼻咽、口咽、硬腭、舌根等)的NK/T细胞淋巴瘤则称鼻型NK/T细胞淋巴瘤。由于此类淋巴瘤具有其本身特殊的特点,其临床特点有别于其他类型的淋巴瘤。既往考虑NK/T细胞淋巴瘤为淋巴瘤的一种亚型,习惯性思维以化疗为主,但是预后差,5年生存率30%15%。其发病可能与CD56表达及EB病毒感染相关的分子机制有关[1],具体机制尚不明确。由于NK/T细胞淋巴瘤多原发于鼻腔,因此称鼻腔NK/T细胞淋巴瘤,而原发于鼻以外(鼻咽、口咽、硬腭、舌根等)的NK/T细胞淋巴瘤则称鼻型NK/T细胞淋巴瘤。由于此类淋巴瘤具有其本身特殊的特点,其临床特点有别于其他类型的淋巴瘤。既往考虑NK/T细胞淋巴瘤为淋巴瘤的一种亚型,习惯性思维以化疗为主,但是预后差,5年生存率30%⁴0%。为了进     

EB病毒潜伏膜蛋白1在鼻咽癌组织中的表达及临床意义

目的 观察EB病毒(EBV)潜伏膜蛋白1(LMP-1)在鼻咽癌(NPC)组织中的表达,探讨LMP-1在NPC诊断、治疗中的意义.方法 采用MaxVision免疫组化的方法检测40例NPC组织及30例鼻咽炎组织中LMP-1的表达,分析LMP-1表达与NPC临床病理特征的关系.结果 LMP-1在NPC组织的阳性表达率显著高于鼻咽炎组织(72.50% vs.16.67%)(P<0.05).LMP-1阳性表达在NPC不同病理学分级及有无颈淋巴结转移方面均无统计学差异(P>0.05).结论 LMP-1在NPC组织中的表达显著高于鼻咽炎组织.应用EBV LMP-1作为NPC辅助诊断及靶向治疗的肿瘤相关分子标志具有一定可行性.     

bcl-2基因产物在EB病毒相关性T细胞淋巴瘤中的表达

目的：探讨抗凋亡基因产物blc－2与鼻咽部T-细胞淋巴瘤发生与EB病毒感染的关系。方法：应用双温PCR技术和免疫组化（SP法）检测18例鼻咽T-细胞淋巴瘤组织中EB病毒DNA和抗凋亡基因产物bcl-2的表达。结果：15例EB病毒DNA阳性病例中7例出现blc－2表达（46.67％）,3例EB病毒DNA阴性病例中有1例bcl-2呈阳性反应（33．33％）。两组间无显著差异（P＞0．05）。结论：鼻咽T细胞淋巴瘤发病可能与EBV感染有关。bcl－2基因产物在鼻咽T-细胞淋巴瘤中异常表达与EB病毒感染无明显关系。     

IgH/TCR基因重排与EB病毒原位杂交联合分析在淋巴瘤诊断中的应用

目的：探讨免疫球蛋白重链/T细胞受体（IgH/TCR）基因重排检测联合EB病毒（EBV）原位杂交在淋巴瘤诊断中的应用,分析EBV＋-B细胞淋巴瘤的细胞学及基因组学特征、鉴别诊断要点,以缩短诊断时间,减少误诊。方法采用IgH/TCR基因重排与EB原位杂交联合分析诊断EBV＋-B细胞淋巴瘤1例,分析其免疫组化特征、EBV原位杂交、基因重排结果。结果 EBV＋-B细胞淋巴瘤临床上主要表现为淋巴结增大,常伴骨髓和外周血浸润。淋巴结活检显示其结构破坏,淋巴滤泡减少,淋巴结高度增生性病变,可见轻至中度异型淋巴细胞,淋巴窦扩张,组织细胞增生。免疫组化证实EBV感染的细胞毒性B细胞构成病变主体;EBV原位杂交显示部分淋巴细胞核阳性;基因重排提示IgH、免疫球蛋白轻链（Igκ）基因发生克隆性重排,TCRγ无克隆性重排。结论 EBV＋-B细胞淋巴瘤从形态学上难以与伯基特淋巴瘤、慢性淋巴细胞白血病等淋巴瘤区分,早期诊断困难。联合应用IgH/TCR基因重排与EBV原位杂交技术对EBV＋-B细胞淋巴瘤的诊断有较高准确性。     

EB病毒感染的病毒学

EB病毒(EBV)感染通常维持在无症状和潜伏状态,主要通过宿主免疫系统,尤其是EBV特异的细胞毒T细胞(CTLs).EBV与几种难治性疾病有关,如EBV相关的噬血性细胞综合征(EBV-AHS)、慢性活动性EBV感染(CAEBV)、血液学和非血液学恶性疾病等.在这些疾病中,EBV感染T/NK细胞引起严重的免疫缺陷,同时伴很高的EBV负荷.近年来,估价这些类型的EBV感染的方法已经改进.实时PCR已用作EBV负荷定量.主要组织相容性复合物(MHC):肽四聚体(peptide tetramer)测定已用于定量EBV特异性CTLs,该类试验已用于EBV相关疾病的处理.     

儿童非霍奇金淋巴瘤EB病毒LMP-1和P53、bcl-2表达的关系

目的探讨儿童NHL EB病毒LMP-1和P53、bcl-2蛋白的表达及关系.方法采用免疫组化Envision法检测64例儿童NHL中LMP-1和P53、bcl-2蛋白.结果 (1)P53蛋白阳性表达39例(60.9%),表达强度与淋巴瘤恶性程度呈正相关;阳性表达率在低恶组与中、高恶性组间有显著性意义,P＜0.01.bcl-2蛋白阳性表达37例(53.8%),bcl高于TCL,低恶性高于高恶性.(2)LMP-1蛋白阳性表达45例(70.3%),阳性表达率与肿瘤恶性程度和年龄有统计学意义,P＜0.01;而与淋巴瘤免疫表型、性别和发病部位无关.LMP-1表达与P53及bcl-2的表达呈正相关.结论 EBV感染是儿童NHL发生发展不可忽视的病毒致病因素,其致病作用可能是通过上调P53、bcl-2蛋白实现的.     

儿童 EB 病毒 T / NK 细胞淋巴组织增殖性疾病诊治进展

EB 病毒( EBV) T/ NK 细胞淋 巴 组 织 增 殖 性 疾 病( Epstein-Barr virus positive T/ NK cell lymphoproliferative diseases,EBV+T/ NK-LPDs)是一组 T 细胞和(或)NK 细胞感染 EBV 后克隆性增殖、浸润组织器官的异质性疾病。 在儿童及青少年中,EBV+T / NK-LPDs 与恶性肿瘤相关的疾病主要包括 T / NK 细胞型慢性活动性 EBV 感染( chronicactive EBV infection,CAEBV) 和儿童系统性 EBV 阳性 T细胞 淋 巴 瘤 ( systemic EBV-positive T-cell lymphoma ofchildhood,STLC)。 2016 年世界卫生组织( WHO) 淋巴肿瘤分类修订版将 STLC 和 HV-LPD 纳入成熟 T / NK 淋巴瘤一类。 儿童 EBV+T / NK-LPDs 发病罕见,在亚洲人和中南美洲及墨西哥的土著居民中发病率较高,临床病程从急性暴发性到慢性迁延性,预后差异大。 其中 CAEBV临床表现广泛,从皮肤型 CAEBV 如种痘水疱病样淋巴组织增生性疾病 ( hydroa vacciniforme-like lymphoproliferative disorder, HV-LPD) 和 重 症 蚊 虫 叮 咬 过 敏 反 应 ( severemosquito bite allergy,sMBA)到以发热、肝脾淋巴结肿大等为表现的系统性 CAEBV。目前该类疾病发病机制尚不明确,地区和人种分布的模式提示 EBV 感染与免疫应答相关的遗传易感性可能和此病发生有关。 EBV+T / NK-LPDs 发病不可 逆, 具 有 向 噬 血 细 胞 性 淋 巴 组 织 细 胞 增 生 症(hemophagocytic lymphohistiocytosis,HLH)、淋巴瘤/ 白血病进展的风险而危及生命,采用联合化疗、细胞疗法以及靶向药物治疗旨在控制病情活动、延缓疾病进展,但疗效欠佳,异基因造血干细胞移植仍然是目前唯一有效的治疗策略。 近年来对 EBV+T / NK-LPDs 报道逐年增加,本文主要综述其临床病理特征、药物治疗研究进展。     

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.     

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.     

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.