骨髓增生异常综合征和再生障碍性贫血等细胞遗传学…

为了探讨骨髓细胞遗传分析在鉴别诊断骨髓增生异常综合征（ＭＤＳ）和再生障碍性贫血（ＡＡ）等不同血液病中的意义，我们联合应用骨髓细胞Ｒ－带核型分析和组妹染色单体分化（ＳＣＤ）检测，对３３４例ＭＤＳ，ＡＡ等不同血液病进行分析并随访。结果表明：（１）ＲＡ／ＡＡ，ＲＡ／ＩＴＰ和ＲＡ／ＨＡ等可疑ＲＡ即为不典型ＲＡ或异早期ＲＡ；（２）骨髓细胞从ＳＣＤ阳性转为ＳＣＤ阴性是骨髓细胞癌变过程：（３）骨髓细胞ＳＣＤ检测     

骨髓增生异常综合征预后因素分析

目的：探讨ＭＤＳ初诊时临床表现及实验室多参数对预后的影响。以利于采取有效的防治对策。方法：采用病例对照方法研究不同年龄、性别、初诊临床表现、ＦＡＢ分型、实验室检查的ＭＤＳ患者的转白率和中数生存期，并对ＭＤＳ死亡危险因素进行多元回归分析。结果：剧烈骨痛、Ｈｂ＜ ３０ｇ／Ｌ、外周血粒系发育异常、ＲＡＥＢ、ＲＡＥＢ－Ｔ ＭＤＳ亚型、骨髓或外周血原始细胞＞ ５％ 、伴发ＭＦ和ＡＬＩＰ（＋ ）、－ ７／７ｑ－ ，＋ ８ 染色体异常或复合染色体异常为ＭＤＳ预后不良因素。而Ｈｂ＞ ９０ ｇ／Ｌ、核型正常或单纯５ ｑ－ 、２０ ｑ－ 、１３ ｑ－ 则预后较好。结论：ＭＤＳ患者初诊时临床表现、实验室指标与预后有关。综合分析上述因素将可能提供ＭＤＳ有价值的预后信息。     

胃癌组织5q微卫星不稳定性与APC/MCC基因杂合性缺失的研究

目的探讨５ｑ微卫星不稳定性（ＭＳＩ）与ＡＰＣ／ＭＣＣ基因杂合缺失（ＬＯＨ）的关系。方法应用ＰＣＲ－ＳＳＬＰ及ＰＣＲ－ＲＦＬＰ技术分析５２例手术切除胃癌组织中ＭＳＩ及ＡＰＣ／ＭＭＣ基因ＬＯＨ。结果５ｑＭＳＩ检出率为３４．０％（１６／４７）,ＡＰＣ／ＭＣＣ基因ＬＯＨ率为３１．４％（１１／３５）。早期胃癌５ｑＭＳＩ阳性率为６６．７％（２／３）,ＡＰＣ／ＭＣＣＬＯＨ率为５０％（１／２）;进展期分别为３１．８（１４／４４）,３０．３％（１０／３３）。两组间无显著差别（Ｐ＞０．０５）。ＭＳＩ及杂合缺失与肿瘤大小、浸润深度、淋巴结转移及临床分期无关。粘液（印戒）细胞癌ＡＰＣ／ＭＣＣＬＯＨ率（５５．６％）显著高于高、中分化管状腺癌（Ｐ＜０．０５）。胃、肠两型胃癌５ｑＭＳＩ及ＡＰＣ／ＭＣＣＬＯＨ差异无显著性及５ｑＭＳＩ与ＡＰＣ／ＭＣＣＬＯＨ无相关性（Ｐ＞０．０５）。结论染色体５ｑＭＳＩ有ＡＰＣ／ＭＣＣ基因ＬＯＨ在两型胃癌的早期发生及发展中起一定作用。染色体５ｑ可能是胃癌的易感部位。     

自体外周血干细胞的动员和采集及其移植效果的研究

对２２例自体外周血干细胞移植（ＡＰＢＳＣＴ）的三种动员方案、采集方法及移植的外周血干细胞（ＰＢＳＣ）数量与造血重建关系，进行了研究。２２例中急性白血病１１例，多发性骨髓瘤６例，非何杰金淋巴瘤４例，晚期乳癌１例。三组动员方案：化疗十四氢叶酸＋氟美松；化疗＋ｒｈＧＭ－ＣＳＦ（重组人粒巨噬细胞集落刺激因子）＋氟美松；化疗＋ｒｈＧ－ＣＳＦ（重组人粒细胞集落刺激因子）＋氟美松。用流式细胞计双染直接免疫荧光法测定ｒｈＧ－ＣＳＦ方案组中７例ＣＤ３４＋／ＣＤ３３￣＋细胞。结果表明：（１）ｒｈＧ－ＣＳＦ方案组的ＰＢＳＣ产率最高，平均每例ＭＮＣ（单个核细胞）（８．２９±６．１４）×１０￣８／ｋｇ，ＣＦＵ－ＧＭ（粒单系祖细胞集落生成单位）（２１．３５±１７．２４）×１０￣４／ｋｇ。（２）ＣＤ３４＋细胞数与ＭＮＣ及ＣＦＵ－ＧＭ数大致相关。ＣＤ３４￣＋细胞在动员前外周血中多为０或＜０．５％，动员后约在用ｒｈＧ－ＣＳＦ后６～８天明显增多，就可连续每日采集，如达到≥５×１０￣５／ｋｇ即可停止。（３）采集与回输的ＰＢＳＣ数量是决定造血重建的关键。     

大肠癌组织APC／MCC和DCC基因杂合缺失的研究

为评估ＡＰＣ／ＭＣＣ和ＤＣＣ基因在大肠癌发生和发展中的作用，采用聚合酶链反应（ＰＣＲ）技术，并配合限制性片段长度多态现象（ＲＦＬＰ）分析，对４１例大肠癌患者的组织ＡＰＣ／ＭＣＣ（位于染色体５ｑ２１）和ＤＣＣ基因（位于染色体１８ｑ２１．３）杂合缺失（ＬＯＨ）进行研究。ＡＰＣ基因ＬＯＨ率为２８．０％（７／２５），ＭＣＣ基因ＬＯＨ率为３６．４％（８／２２），两者综合分析ＬＯＨ率为３８．９％（１４／３８）。ＤＣＣ基因ＬＯＨ率为５５．３％（２１／３８）。ＤＣＣ基因在有淋巴结转移组的ＬＯＨ率（８０．０％）显著高于无淋巴结转移组（３９．１％）（Ｐ＜０．０５），在ＤｕｋｅｓＣ、Ｄ期组的ＬＯＨ率（７１．４％）显著高于Ａ、Ｂ期组（３５．３％）。以上结果提示，ＡＰＣ／ＭＣＣ和ＤＣＣ基因的ＬＯＨ是大肠癌常见的基因改变，ＤＣＣ基因ＬＯＨ的测定有可能成为大肠癌病人预后估计的指标。     

类风湿性关节炎合并恶性血液病四例

报告４例类风湿性关节炎（ＲＡ）合并恶性血液病。１　病例资料见附表。附表　４例ＲＡ合并恶性血液病患者的临床资料病例号年龄性别ＲＡ的临床特点二病发生间隔时间血象骨髓象其他诊断治疗预后１６５男双手近指关节、双肘、膝对称性肿痛及活动受限。晨僵５～６ｈ／ｄ。用消炎止痛药（ＮＳＡＩＤＳ）多年及金制剂治疗２个月２２年Ｈｂ７４ｇ／ＬＷＢＣ１．６×１０９／Ｌ,Ｎ０．３４,Ｌ０．４２,早幼粒０．１９,ＰＬＴ６８×１０９／ＬＡＮＬＬ－Ｍ３ａ粒系显著增生,以早幼粒为主占６９％。ＣＤ１１ｂ（＋）ＣＤ１３（＋）ＣＤ３３（＋…     

1例伴有Ph染色体的MDS－RAS

１例伴有Ｐｈ染色体的ＭＤＳ－ＲＡＳ哈尔滨医科大学附属第二医院血液病研究所蔡莹，王孟学，卢远清，孟德润据报道，在骨髓增生异常综合征（ＭＤＳ）患者中，约１／３～１／２具有明显的染色体异常，现报道１例伴有Ｐｈ易位的ＭＤＳ－ＲＡＳ如下：患者，男，６３岁。主诉...     

CD116在急性白血病中的表达及临床意义

目的：探讨ＣＤ１１６在急性白血病中的表达及临床意义。方法：对１１４例急性白血病者进行免疫表型及细胞遗传学分析。结果ＣＤ１１６在急性淋巴细胞白轿病（ＡＬＬ）中无阳性表达，而在急性髓性细胞白血病（ＡＭＬ）中阳性表达率为４２．４％；ＣＤ１１６在ＡＭＬ各亚型间出现的频率存在明显差异，阳性率Ｍ５为８３．３％，Ｍ４为４０．０％，Ｍ３和Ｍ２分别为２７．２％和１５．０。２例Ｍ５患者出现染色体＋８异常，伴ＣＤ１１６     

环孢霉素A治疗狼疮性肾炎对血尿可溶性白介素2受体的影响

本文观察环孢霉素（ＣｓＡ）治疗１６例重症ＬＮ患者，对血尿可溶性白介素２受体（ＳＩＬ－２Ｒ）及外周血Ｔ淋巴细胞亚群（ＣＤ４＋／ＣＤ８＋细胞）的影响。结果ＣｓＡ治疗后，ＬＮ患者血尿ＳＩＬ－２Ｒ均有明显下降（Ｐ＜０．０１），外周血ＣＤ４＋细胞亦有下降趋势；同时伴有血清免疫学异常及临床肾损害的明显改善。本文提示ＳＩＬ－２Ｒ可作为ＬＮ活动度的一项敏感指标；ＣｓＡ可能通过抑制Ｔ淋巴细胞活性，减少被激活的淋巴细胞释放ＳＩＬ－２Ｒ，从而取得治疗ＬＮ的良好疗效。     

老年人红细胞膜唾液酸含量与红细胞免疫功能的相关性

目的探讨老年人红细胞膜唾液酸（ＲＢＣｍ－ＳＡ）与红细胞免疫功能的相关性。方法采用Ｂｉａｌｓｃｈｅ试剂法检测ＲＢＣｍ－ＳＡ，Ｆ－８８３６化学比色法检测血浆唾液酸（Ｐ－ＳＡ），红细胞免疫粘附试验观察红细胞Ｃ３ｂ受体花环率（ＲＲＣＦ）。结果老年急性心肌梗死（ＡＭＩ）组和脑梗塞（ＡＣＩ）组的ＲＢＣｍ－ＳＡ分别为３０．８±４．３和３１．３±４．４μｇＮＡＮＡ／ｍｇ膜蛋白，ＲＲＣＦ分别为１６．７％±３．５％和１６．０％±３．６％，均低于老年对照组（Ｐ＜０．０１或０．０５），老年对照组均低于非老年对照组（均为Ｐ＜０．０５）；ＡＭＩ和ＡＣＩ患者的Ｐ－ＳＡ分别为２．４±０．４和２．４±０．３ｍｍｏｌ／Ｌ，均高于老年对照组（均为Ｐ＜０．０５），老年对照组则高于非老年对照组（Ｐ＜０．０５）。老年患者和老年对照组的ＲＢＣｍ－ＳＡ与ＲＲＣＦ均呈正相关，而ＲＢＣｍ－ＳＡ与Ｐ－ＳＡ均呈负相关。结论老年人红细胞Ｃ３ｂ受体花环率降低与ＲＢＣｍ－ＳＡ代谢障碍有关。     

Aspirin-Intolerant Asthma (AIA) Assessment Using the Urinary Biomarkers, Leukotriene E(4) (LTE(4)) and Prostaglandin D(2) (PGD(2)) Metabolites

The clinical syndrome of aspirin-intolerant asthma (AIA) is characterized by aspirin/nonsteroidal anti-inflammatory drug intolerance, bronchial asthma, and chronic rhinosinusitis with nasal polyposis. AIA reactions are evidently triggered by pharmacological effect of cyclooxygenase-1 inhibitors. Urine sampling is a non-invasive research tool for time-course measurements in clinical investigations. The urinary stable metabolite concentration of arachidonic acid products provides a time-integrated estimate of the production of the parent compounds in vivo. AIA patients exhibits significantly higher urinary concentrations of leukotriene E(4) (LTE(4)) and 1,15-dioxo-9α-hydroxy-2,3,4,5-tetranorprostan-1,20-dioic acid (tetranor-PGDM), a newly identified metabolite of PGD(2), at baseline. This finding suggests the possibility that increased mast cell activation is involved in the pathophysiology of AIA even in a clinically stable condition. In addition, lower urinary concentrations of primary prostaglandin E(2) and 15-epimer of lipoxin A(4) at baseline in the AIA patients suggest that the impaired anti-inflammatory elements may also contribute to the severe clinical outcome of AIA. During the AIA reaction, the urinary concentrations of LTE(4) and PGD(2) metabolites, including tetranor-PGDM significantly and correlatively increase. It is considered that mast cell activation probably is a pathophysiologic hallmark of AIA. However, despite the fact that cyclooxygenease-1 is the dominant in vivo PGD(2) biosynthetic pathway, the precise mechanism underlying the PGD(2) overproduction resulting from the pharmacological effect of cyclooxygenease-1 inhibitors in AIA remains unknown. A comprehensive analysis of the urinary concentration of inflammatory mediators may afford a new research target in elucidating the pathophysiology of AIA.     

Expression, purification, and characterization of human hemoglobins Gower-1 (zeta(2)epsilon(2)), Gower-2 (alpha(2)epsilon(2)), and Portland-2 (zeta(2)beta(2)) assembled in complex transgenic-knockout mice

Embryonic zeta- and epsilon-globin subunits assemble with each other and with adult alpha- and beta-globin subunits into hemoglobin heterotetramers in both primitive and definitive erythrocytes. The properties of these hemoglobins-Hbs Gower-1 (zeta(2)epsilon(2)), Gower-2 (alpha(2)epsilon(2)), and Portland-2 (zeta(2)beta(2))-have been incompletely described as they are difficult to obtain in quantity from either primary human tissue or conventional expression systems. The generation of complex transgenic-knockout mice that express these hemoglobins at levels between 24% and 70% is described, as are efficient methods for their purification from mouse hemolysates. Key physiological characteristics-including P(50), Hill coefficient, Bohr effect, and affinity for 2,3-BPG-were established for each of the 3 human hemoglobins. The stability of each hemoglobin in the face of mechanical, thermal, and chemical stresses was also determined. Analyses indicate that the zeta-for-alpha exchange distinguishing Hb Portland-2 and Hb A alters hemoglobin O(2)-transport capacity by increasing its P(50) and decreasing its Bohr effect. By comparison, the epsilon-for-beta exchange distinguishing Hb Gower-2 and Hb A has little impact on these same functional parameters. Hb Gower-1, assembled entirely from embryonic subunits, displays an elevated P(50) level, a reduced Bohr effect, and increased 2,3-BPG binding compared to Hb A. The data support the hypothesis that Hb Gower-2, assembled from reactivated epsilon globin in individuals with defined hemoglobinopathies and thalassemias, would serve as a physiologically acceptable substitute for deficient or dysfunctional Hb A. In addition, the unexpected properties of Hb Gower-1 call into question a common hypothesis for its primary role in embryonic development.     

Comparison of FEV(3), FEV(6), FEV(1)/FEV(3) and FEV(1)/FEV(6) with usual spirometric indices

Background and objective: Pulmonary function tests play an important role in the management of pulmonary diseases. One of the tests that are widely used is spirometry. Performing an acceptable spirometry manoeuvre according to the standards set by the American Thoracic Society/European Respiratory Society is difficult. The aim of this study was to compare forced expiratory volume in 3 s (FEV₃) and forced expiratory volume in 6 s (FEV₆) with forced vital capacity (FVC), and forced expiratory volume in 1 s FEV₁/FEV₃ and FEV₁/FEV₆ with FEV₁/FVC, in order to substitute the usual spirometric manoeuvres with manoeuvres that are easier to perform. Methods: In a cross‐sectional study, spirometry was performed for 588 subjects who were referred for occupational health evaluations. The accuracy of FEV₃, FEV₆, FEV₁/FEV₃ and FEV₁/FEV₆ was compared with that of FVC and FEV₁/FVC. Chi‐square tests and kappa tests were used to analyse the data. Results: Individuals with normal (n = 297) and abnormal spirometry (n = 291) were evaluated. The sensitivity, specificity, positive predictive value and negative predictive value of FEV₁/FEV₆, as compared with that of FEV₁/FVC for detecting obstruction, were 93.56, 99.32, 98.95 and 96.09, respectively. The sensitivity, specificity, positive predictive value and negative predictive value of FEV₆, as compared with that of FVC for detecting restriction, were 96.68, 98.65, 96.68 and 98.65, respectively. Conclusions: FEV₆ and FEV₁/FEV₆ can be used as surrogates for FVC and FEV₁/FVC, respectively, and these parameters showed acceptable sensitivity, specificity, positive predictive value and negative predictive value for occupational health evaluations.     

PCR-based diagnosis of the Filipino (--(FIL)) and Thai (--(THAI)) alpha-thalassemia-1 deletions

In southeast Asia, the carrier frequency of two-gene alpha-thalassemia deletions is quite high, ranging from 4% to 14% depending on the population. The most common alpha-thalassemia-1 deletion is the so-called southeast Asian deletion (--(SEA)). In addition, a significant proportion of cases involve two other deletions, the Filipino (--(FIL)) and Thai (--(THAI)) deletions. In this report, we identify the deletion breakpoints for the (--(FIL)) and (--(THAI)) deletions, and describe PCR-based protocols for rapid and reliable DNA diagnosis of these deletions.