白血病骨髓细胞ras癌基因产物P21蛋白的免疫组化检测

用LSAB（Labelled streptavidin biotin method）免疫组化法对30例白血病骨髓细胞进行了P_（21）蛋白免疫组化检测。其中急性粒细胞性白血病（AML）14例,9例阳性,阳性率57.14%。急性淋巴细胞性白血病（ALL）11例,1例阳性,阳性率9.09%。1例慢性粒细胞性白血病（CML）为阴性。2例CML急变期（CML BP）,1例为阳性。2例慢性淋巴细胞性白血病急变期（CLL BP）均为阳性。结果显示AML的P_（21）蛋白表达率较高。将AML与ALL进行统计学分析,P=0.03,提示表达率与白血病类型有明显相关性。     

WT1基因在白血病中的表达及临床意义

目的　探讨WT1基因在白血病中的作用。方法　用定量RT -PCR方法检测病人外周血或骨髓单个核细胞WT1mRNA表达。结果　 5 0例白血病患者中 ,41例WT1mRNA表达增高 ,阳性率为 82 0 %。急性髓细胞白血病 (AML)和急性淋巴细胞白血病 (ALL)阳性率分别为 84 0 %和 93 8% ,两组无显著差异 (P >0 0 5 ) ,慢性粒细胞白血病 (CML)的WT1mRNA阳性率为 6 6 7% ,其中慢性期均阴性 ,加速期和急变期均阳性。 17例完全缓解患者中 ,15例 (85 2 % )WT1mRNA转阴 ,复发患者WT1mRNA再次升高。结论　WT1mRNA表达的测定对白血病微小残留病检测具有重要意义     

髓系白血病中EVI1基因的表达及其临床意义

目的研究EVI1基因在成人急性髓系白血病(AML)和慢性粒细胞白血病(CML)中的表达及其临床意义。方法采用多重逆转录-聚合酶链反应(多重RT-PCR)技术分析2002年9月至2005年3月华中科技大学同济医学院附属同济医院收治的45例AML和43例CML骨髓单个核细胞中EVI1基因mRNA的表达,分析EVI1mRNA阳性白血病患者的临床特征及疗效。结果45例AML患者中有8例(17.8%)EVI1阳性,其中M11例、M23例、M54例。43例CML患者中有8例(18.6%)EVI1阳性,其中慢性期2例,占5.7%(2/35),加速期与急变期各3例,均占75.0%(3/4),加速期与急变期组的EVI1基因表达率高于慢性期组(P<0.01)。EVI1阳性的AML患者早期病死率高;EVI1基因阳性表达与CML白血病临床分期及预后相关。结论EVI1基因的高表达在髓系白血病的发生中,特别是在慢性粒细胞白血病慢性期向急性期转化中起重要作用。     

白血病患者Prame基因的表达及其与WT1基因比较的临床意义

目的：探讨Prame(黑色素瘤特异性抗原)在白血病患者中的表达及其临床意义。方法：应用逆转录—聚合酶链反应(RT—PCR)测定58例白血病患者Prame mRNA的表达，并与WTl mRNA的表达相比较。结果：急性髓细胞性白血病(AML)患者Prame阳性表达率为52．2％，急性淋巴细胞性白血病(ALL)患者Prame阳性表达率为66．7％，慢性粒细胞性白血病(CML)急性变患者Prame阳性表达率为55．6％；慢性及加速期CML患者ll例、l0名正常人外周血及l0例非血液病患者骨髓细胞均未见Prame mRNA表达，其中l例AML和5例ALL患者Prame阳性而WT1阴性。对2例Prame阳性和4例Prame、WTl均阳性的患者短期随访发现所有患者化疗后Prame均有不同程度的下降。l例复发患者Prame表达再次升高且早于WTl l个月，余3例白血病患者Prame和WTl表达的波动呈正比。结论：免疫抗原Prame是白血病的一个重要标记基因，与病程进展密切相关，有望成为白血病微小残留病灶检测和进行白血病免疫治疗的靶基因。     

老年白血病bcr/abl融合基因的表达及其临床意义

目的　观察bcr/abl融合基因在老年白血病的表达及其临床意义。　 方法 　应用逆转录聚合酶链反应 (RT PCR)一步法检测 62例老年白血病患者bcr/abl融合基因的表达。　 结果 　 62例患者中bcr/abl融合基因阳性 5 3例 ,阳性率 85 5 % ,其中急性淋巴细胞白血病 (ALL) 17例 ,阳性 9例 (5 2 9% ) ;慢性粒细胞白血病 (CML)45例 ,阳性 44例 (97 88% )。DOCP方案治疗 7例bcr/abl ALL患者完全缓解 (CR)率 2 8 6% ,6例bcr/abl-ALL患者CR率 66 7% (P <0 0 1)。　 结论　bcr/abl融合基因检测有助于CML和ALL的临床诊断、治疗选择、微小残留病变 (MRD)监测以及预后判断 ;老年ALLbcr/abl融合基因阳性率较高 ,可能是其治疗效果较差的原因之一 ;bcr/abl ALL患者CR率明显低于bcr/abl-ALL患者 ;RT PCR一步法特异性好、敏感性高、简便快速 ,尤其适用于MRD的临床监测。     

髓系抗原、P-糖蛋白和CD34抗原在急性淋巴细胞白血病中的表达及其意义

目的　探讨急性淋巴细胞白血病 (ALL)的髓系抗原、P 糖蛋白 (P gp)和CD3 4 表达特点及其与预后的关系。方法　采用间接免疫荧光法标记流式细胞仪 (FCM )检测 84例初治ALL患者的免疫表型。结果　ALL髓系抗原阳性率为 17.8% ,其中CD13 阳性最常见。CD3 4 表达阳性率为45 .3 % ,与髓系抗原表达和治疗缓解率无显著相关性。髓系抗原阳性组病例 (My ALL)肝脾肿大明显 ,白细胞总数增高显著 ,完全缓解 (CR)率明显低于阴性组病例 (P <0 .0 1)。P gp阳性表达率为 3 2 .1% ,P gp表达阳性与My ALL化疗效果有相关性。结论　My ALL细胞对于常规诱导缓解方案不敏感 ,选择兼顾ALL AML的方案可提高治疗效果。P gp高度表达与低CR率有密切关系     

白血病细胞共刺激分子和MHC分子的表达分析

目的：检测各型白血病细胞表面共刺激分子和MHC分子的表达情况。方法：采集66例初诊白血病患者骨髓标本细胞及15例正常人外周血标本，分离单个核细胞，采用直接荧光抗体标记，应用流式细胞仪检测细胞表面CD80（B7—1）、CD86（B7—2）、HLA-DR和HLA-ABC的表达。结果：所有66白血病患者，仅1例急性髓细胞白血病（AML）与1例B-ALL表达CDS0，其余均为CD80阴性表达;CD88在急性淋巴细胞白血病（ALL）及慢性髓细胞白血病（CML）组的表达低于健康对照；HLA-DR的表达仅在CML细胞低于对照。所有白血病及正常人PBMC上HLA-ABC表达均为强阳性。在45例急性髓细胞白血病（AML）中，CD86阳性占18例（40％），CD86的表达在M4和M5亚型AML中最高；HLA-DR阳性25例（55％），HLA—DR在M2、M4、M5的表达明显高于其它亚型，而在M3型表达HLA-DR均为阴性；CD80、HLAABC在不同FAB亚型的表达无差异。CD86在高危核型及Ph＋组的表达低于低危核型组。共刺激分子及MHC分子的表达与诱导化疗的疗效未发现有相关。结论：各型白血病存在不同程度的B7或HLA-DR表达的缺陷。上调HLA-Ⅱ抗原及协同刺激分子在白血病细胞上的表达对设计高效的白血病免疫治疗方案具有重要意义。     

急性淋巴细胞白血病Ki-67抗原和Bcl-2的表达及临床意义

目的：通过增殖相关抗原Ki-67和抗凋亡蛋白Bcl-2的检测，观察其在急性淋巴细胞白血病（ALL）和慢性淋巴细胞白血病（CLL）中的表达，探讨其与ALL免疫学分型，临床疗效和预后的关系。方法：采用链霉菌抗生物素蛋白-碱性磷酸酶（SAP）免疫组织化学染色的方法，对120例白血病患者的骨髓或外周血进行Ki-67抗原和Bcl-2蛋白的检测。结果：（1）Ki-67抗原在成人ALL中的表达高于其在急性非淋巴细胞白血病（ANLL），CLL中的表达，Bcl-2蛋白在成人ALL中的表达明显低于ANLL，CLL中的表达。（2）在成人ALL各免疫表型中，T细胞，伴有髓系抗原标记的急性淋巴细胞白血病（My^ ALL)的Ki-67和Bcl-2阳性表达率较高。（3）完全缓解（CR）率在Ki-67和Bcl-2两项同时低表达组中最高，在仅一项低表达组中次之，在两项均高表达组中最低。（4）Ki-67高表达组的生存期比低表达组短，且差异有显著性意义。而Bcl-2的表达在两组之间无差异。结论：对成人ALL患者进行增殖相关抗原Ki-67和抗凋亡蛋白Bcl-2的检测，能反映患者肿瘤细胞的增殖活性和凋亡抑制情况，与白血病的类型，临床疗效和预后密切相关。     

CD40抗原和生存素基因在急性髓性白血病细胞中表达及其临床意义

目的探讨急性髓性白血病(AML)细胞的CD40抗原和抗凋亡基因生存素(survivin)mRNA表达及其临床意义。方法应用流式细胞仪和逆转录-PCR方法检测48例初治AML患者细胞的CD40抗原和抗凋亡基因survivin mRNA表达,并结合AML患者临床特征进行分析。结果(1)48例AML患者中25例(52．1％)表达CD40抗原,35例(72．9％)表达survivin mRNA。(2)CD40^ AML组中脾肿大、血小板减少和高白细胞白血病的发生率明显高于CD40^-AML组(36．0％、8．7％),P=0．025;(72．0％、43．5％),P=0．045;(32．0％、4．4％),P=0．024。(3)survivin mRNA在CD40^ AML和CD40^-AML两组中表达差异无显著性(20／25、15／23),P=0．25,但两组中的survivin mRNA表达均明显高于健康对照组(20／25、6／20),P=0．001;(15／23、6／20),P=0．021;48例AML患者中CD40抗原阳性率低于survivin mRNA阳性率(52．1％、72．9％),P=0．041。(4)survivin^ AML化疗完全缓解(CR)率明显低于survivin^-AML(31．4％、69．2％),P=0．018。结论CD40抗原表达和AML的临床血液学特征存在一定关系;表达抗凋亡基因survivin mRNA是AML患者化疗CR率低的原因之一,可能是影响AML患者预后的因素。     

RT-PCR检测SALL4基因在白血病中的表达

目的：检测SALL4基因在白血病细胞中的表达情况。方法：运用RT-PCR技术对35例白血患者及10例正常对照的单个核细胞进行SALL4mRNA表达测定。结果：急性非淋巴细胞白血病（ANLL）患者中,SALL4mRNA表达率为83.3（15/18）;慢性髓细胞白血病（CML）患者SALL4mRNA表达率为100（7/7）;B-ALL患者中,SALL4mRNA表达率为100（6/6）,T-ALL的SALL4mRNA表达率为0（0/4）。对照组10例的SALL4mRNA表达为阴性。ANLL、CML、B-ALL之间SALL4mRNA的表达率比较差异无统计学意义（P〉0.05）,前3组与T-ALL、对照组间SALL4mRNA的表达差异有统计学意义（P〈0.01）。BCR-ABL融合基因与SALL4在ALL、CML组中的表达呈正相关性。结论：ANLL、CML、B-ALL的单个核细胞SALL4mRNA表达阳性,提示SALL4基因可能与白血病的发生相关;B-ALL与T-ALL间的SALL4基因表达差异有统计学意义,提示2者的发病机制可能不同。     

Electrochemical Recovery and Behaviors of Rare Earth (La,Ce, Pr,Nd, Sm,Eu, Gd,Tb, Dy,Ho, Er,Tm, and Yb) Ions on Ni Sheets

The electrochemical behaviors of rare earth (RE) ions have extensively been studied because of their high potential applications to the reprocessing of used nuclear fuels and RE-containing materials. In the present study, we fully investigated the electrochemical behaviors of RE(III) (La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, and Yb) ions over a Ni sheet electrode in 0.1 M NaClO₄ electrolyte solution by cyclic voltammetry between +0.5 and −1.5 V (vs. Ag/AgCl). Amperometry electrodeposition experiments were performed between −1.2 and −0.9 V to recover RE elements over the Ni sheet. The successfully RE-recovered Ni sheets were fully characterized by scanning electron microscopy, energy dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and photoluminescence spectroscopy. The newly reported recovery data for RE(III) ions over a metal electrode provide valuable information on the development of the treatment methods of RE elements.     

Clinical trials update: highlights of the scientific sessions of The American College of Cardiology 2002: LIFE,DANAMI 2, MADIT-2, MIRACLE-ICD,OVERTURE, OCTAVE,ENABLE 1 & 2, CHRISTMAS,AFFIRM, RACE,WIZARD, AZACS,REMATCH, BNP trial and HARDBALL

This article continues a series of reports updating recent research developments of particular interest to personnel involved in the treatment and management of patients with heart failure. This is a summary of selected presentations made at the American College of Cardiology 51st Annual Scientific Session held in Atlanta on 17-20 March 2002. Reports of the following clinical studies are included: LIFE, DANAMI 2, MADIT-2, MIRACLE-ICD, OVERTURE, OCTAVE, ENABLE 1 & 2, CHRISTMAS, AFFIRM, RACE, WIZARD, AZACS, REMATCH, BNP trial and HARDBALL.     

Prevalence,Self-Awareness,Treatment, and Control of Hypertension in Lhasa,Tibet

To investigate the prevalence, self-awareness, and treatment of hypertension in Lhasa, Tibet, a total of 1370 native Tibetan aged ≥18 years were selected, using stratified proportional sampling. The study showed that the prevalence of hypertension was 51.2%, significantly higher in men (56.0%) than in women (48.0%) (P = .004). The hypertension prevalence increased with increasing age (77.8% in 60–74 y and 82.5% in ≥75 y groups) and was higher in urban, suburban, or agricultural area than in pastoral area (P < .001). The self-awareness, treatment, and control rate of hypertension were 63.5%, 24.3% and 7.7%, respectively. In multivariable regression analysis, age, urban residence, amount of daily intake of fat and oil, and body mass index <18.5 kg/m² were independently associated with hypertension. In conclusion, hypertension was highly prevalent among native Tibetan people in Lhasa, and the rates of self-awareness, treatment, and control of hypertension were low.     

Lack of effect of colesevelam HCl on the single-dose pharmacokinetics of aspirin,atenolol, enalapril,phenytoin, rosiglitazone,and sitagliptin

Aims

Drug interactions with bile acid sequestrants are primarily due to the potential of these agents to bind to concomitant drugs. Six clinical studies were performed to determine the effects of colesevelam on the pharmacokinetics of aspirin, atenolol, enalapril, phenytoin, rosiglitazone, and sitagliptin.

Methods

All six studies enrolled healthy subjects aged 18–45 years. The phenytoin study used a single-dose, three-period crossover design (phenytoin alone, phenytoin simultaneously with colesevelam, and phenytoin 4 h before colesevelam). The other studies used a two-period crossover design (test drug alone and test drug simultaneously with colesevelam). Colesevelam (3750 mg once daily) was dosed throughout the pharmacokinetic sampling period. After each single dose of the test drug, serial blood samples were collected for determination of plasma drug concentrations and calculation of pharmacokinetic parameters.

Results

For all six test drugs, 90% CIs for geometric least-squares mean ratios of AUC and C_max for the measured analytes were within specified limits, indicating no interaction between the test drug and colesevelam.

Conclusions

Aspirin, atenolol, enalapril, rosiglitazone, and sitagliptin may be taken with colesevelam. Although the phenytoin study indicated no pharmacokinetic interaction, phenytoin should continue to be taken ≥4 h before colesevelam in accordance with current prescribing information.     

Biliary microlithiasis,sludge,crystals,microcrystallization,and usefulness of assessment of nucleation time

BACKGROUND:The process of microcrystallization,its sequel and the assessment of nucleation time is ignored.This systematic review aimed to highlight the importance of biliary microlithiasis,sludge,and crystals,and their association with gallstones,unexplained biliary pain,idiopathic pancreatitis, and sphincter of Oddi dysfunction.DATA SOURCES:Three reviewers performed a literature search of the PubMed database.Key words used were"biliary microlithiasis","biliary sludge","bile crystals","cholesterol crystallisation","bile microscopy","microcrystal formation of bile","cholesterol monohydrate crystals","nucleation time of cholesterol","gallstone formation","sphincter of Oddi dysfunction"and"idiopathic pancreatitis".Additional articles were sourced from references within the studies from the PubMed search.RESULTS:We found that biliary microcrystals account for almost all patients with gallstone disease,7%to 79%with idiopathic pancreatitis,83%with unexplained biliary pain, and 25%to 60%with altered biliary and pancreatic sphincter function.Overall,the detection of biliary microcrystals in gallstone disease has a sensitivity ranging from 55%to 87%and a specificity of 100%.In idiopathic pancreatitis,the presence of microcrystals ranges from 47%to 90%.A nucleation time less than 10 days in hepatic bile or ultra-filtered gallbladder bile has a specificity of 100%for cholesterol gallstone disease.CONCLUSIONS:Biliary crystals are associated with gallstone disease,idiopathic pancreatitis,sphincter of Oddi dysfunction, unexplained biliary pain,and post-cholecystectomy biliary pain.Pathways of cholesterol super-saturation,crystallisation, and gallstone formation have been described with scientificsupport.Bile microscopy is a useful method to detect microcrystals and the assessment of nucleation time is a good method of predicting the risk of cholesterol crystallisation.     

Clinical trials update from the American College of Cardiology 2008: CARISMA, TRENDS, meta-analysis of Cox-2 studies, HAT, ON-TARGET, HYVET, ACCOMPLISH, MOMENTUM, PROTECT, HORIZON-HF and REVERSE

This article provides information and a commentary on trials relevant to the pathophysiology, prevention and treatment of heart failure, presented at the American College of Cardiology. Unpublished reports should be considered as preliminary data, as analyses may change in the final publication. CARISMA investigated the use of implantable loop recorders for detecting life-threatening arrhythmias in patients with LVSD after MI and found that brady- and ventricular tachy-arrhythmias predicted an adverse prognosis. The TRENDS study showed that the burden of atrial fibrillation detected by pacemakers or defibrillators predicted the risk of embolic events but not with sufficient precision to justify changes in anti-thrombotic management. A meta-analysis of six trials reported an increased cardiovascular risk associated with celecoxib, particularly for heart failure, which was related to dose and baseline cardiovascular risk. The HAT study failed to show a benefit of providing post-MI patients with a home defibrillator. MOMENTUM, a study of a device designed to augment aortic blood flow, was stopped early due to increased bleeding risk. Results from PROTECT support the use of rolofylline 30 mg/day in acute heart failure, a definitive study is now underway. Istaroxime, an agent that appears to have both inotropic and lusitropic effects, improved haemodynamics when added to standard therapy in patients stabilised after admission with heart failure in HORIZON-HF. The REVERSE study suggested that CRT improves ventricular function and reduces morbidity even in patients with few or no symptoms of heart failure and may delay or prevent worsening heart failure.