晚期日本血吸虫病患者肝窦病变的观察

目的 观察晚期日本血吸虫病（晚血）患者肝窦病变，并探讨其与肝纤维化程度、肝功能的关系。方法 26例晚血患者肝活检标本和5例正常肝标本行常规病理染色和天狼猩红染色，进行肝纤维化程度的半定量分析；应用鼠抗人Ⅳ型胶原（C—IV）单克隆抗体和兔抗人层粘蛋白（LN）多克隆抗体进行免疫组织化学（免疫组化）染色，阳性者进行定量检测；放射免疫法检测血清透明质酸（HA），自动生化分析仪检测肝功能；对其中5例患者和2例正常肝标本进行透射电镜观察。结果 肝纤维化程度为Ⅰ级、Ⅱ级和Ⅲ级的患者分别为5、11和10例，晚血患者肝窦壁C-Ⅳ和LN表达增强，并与肝纤维化程度及部分肝功能指标水平相关（P＜0．05或P＜0．01），与血清HA水平无关（P〉0．05）。晚血患者肝窦内皮细胞（SEC）失窗孔及SEC下可见基底膜（BM）的形成，SEC胞浆内出现Weibel、Palade等发现的小体（简称WP小体），肝窦腔内有脱落的肝细胞微绒毛。结论晚血患者肝窦存在病变，与肝纤维化程度及肝功能改变有关。     

日本血吸虫病肝纤维化诊断研究进展

机体感染日本血吸虫后 ,虫卵在肝脏沉积并释放可溶性抗原 ,刺激巨噬细胞释放一系列细胞因子 (TNF- α、TGF- β、IL- 1等 ) ,激活枯否细胞 (KC)、星状细胞 (HSC) ,使前胶原m RNA表达增加 ,促进胶原与非胶原细胞外间质 (L N、HA等 )合成、分泌 ,成纤维细胞增生 ,产生大量胶原纤维沉积于肝脏 ,沿肝内门脉小分支形成特征性的血吸虫性干线型肝纤维化 [1～ 3 ]。在血吸虫病肝纤维化早期及时祛除病因 ,肝纤维化多能终止或部分逆转。当肝纤维化进一步发展 ,可由干线型纤维化形成肝硬化 ,临床表现出晚期血吸虫病症状体征时 ,虽经彻底祛除病…     

肝母细胞瘤微血管密度的临床意义

目的　探讨肿瘤内微血管密度 (MVD)对肝母细胞瘤的临床意义。方法　应用免疫组化方法检测了 16例肝母细胞瘤患者手术切除石蜡包埋标本中CD3 4的表达 ,根据CD3 4阳性的血管内皮细胞计数来测定肿瘤微血管密度 (MVD)。结果　①未分化型、胚胎型肝母细胞瘤与胎儿型和混合型相比 ,MVD均显著增高 (P <0 0 5 )。②淋巴结转移组较无淋巴结转移组MVD显著增高。③生存组与死亡组MVD差异有统计学意义 ,前者较低 (P <0 0 5 )。结论　MVD是判断肝母细胞瘤预后的一项理想指标。     

日本血吸虫病肝纤维化的临床特点

目的通过检测有关细胞因子及病理学对肝组织标本从细胞、分子水平、组织超微结构等研究日本血吸虫病肝纤维化的发生、发展特点,并探讨合理的防治对策。方法晚期血吸虫病(晚血)包括切脾后、未达晚血标准的脾肿大者及晚血夹杂肝炎者分为A、B、C3组,除进行肝纤维化指标、生化检测和超声显像检测外,另对部分患者作淋巴细胞亚群、细胞膜CD35表达免疫学检测。部分患者作肝组织病理学的免疫组化检查。结果1212例中有94.06%的患者曾接受不同药物的病原治疗。血吸虫间接血凝试验、酶联免疫吸附试验1项或2项均为阳性者3组差异有显著性。肝纤维化4项指标测定中,层黏蛋白、透明质酸3组差异亦有显著性。超声显像肝实质分级3组差异亦有显著性。肝纤维化病理特征研究中,炎症与纤维化呈正相关。晚血肝纤维化时C-I、C-型胶原在肝汇管区、中央静脉、肝窦等部位含量均明显增加,肝窦本身出现扩张与狭窄两种病理改变。结论血吸虫病的病理不仅属窦前性改变,肝窦本身病变在肝纤维化的发生中起着重要作用。彻底杀虫治疗或切脾后,肝纤维化仍可继续发展,今后尚需加强随访与防治,减少晚血的发生与发展。     

CD31、CD34和CD105蛋白在食管鳞状细胞癌组织微血管中的表达及意义

目的探讨CD31、CD34和CD105蛋白表达在食管鳞状细胞癌（ESCC）发生、发展中的作用。方法应用免疫组化SP法对50例ESCC和10例正常食管黏膜组织标本进行标记染色,按Weidner法计算三种蛋白标记物的肿瘤组织微血管密度（MVD）。结果在ESCC及正常食管黏膜组织中MVD-CD31、MVD—CD34及MVD-CD105均依次降低,组间比较尸〈0．01;MVD-CD31、MVD—CD34与ESCC的浸润深度及淋巴结转移密切相关（P〈0．05）,MVD—CD105与ESCC的TNM分期、浸润深度及淋巴结转移密切相关（P〈0．01）;ESCC组织中MVD—CD31、MVD—CD。均显著高于MVD-CD105（P〈0．01）。结论CD31、CD34和CD105蛋白表达在ESCC发生、发展和转移中起重要作用;联合检测三者可望为判断ESCC发展及利用血管抑制剂治疗提供理论依据。     

强肝胶囊治疗日本血吸虫病早期肝纤维化的临床研究

目的评估强肝胶囊治疗日本血吸虫病早期肝纤维化的效果及可能的副作用。方法138例日本血吸虫病早期肝纤维化病人随机分为试验组(68例)和对照组(70例)。试验组服强肝胶囊2.0g/次,每日2次,连续6个月,加维生素类和肝泰乐。对照组服用安慰剂加维生素类和肝泰乐等一般护肝药。在治疗前、治疗后分别进行肝脏B超、肝功能、血清肝纤维化四项指标,即透明质酸(HA)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(ⅣC)和层粘蛋白(LN)检查以及临床症状改善情况观察,比较试验组和对照组间结果有无差异。结果治疗前,试验组与对照组间各项指标差异均无显著意义(均为P>0.05)。治疗后的临床症状,试验组比对照组改善明显(P<0.01);试验组肝脏纤维化程度从Ⅱ级降到Ⅰ级的人数多于对照组,但差异无显著性(均为P>0.05);二组间转氨酶恢复正常的人数的比例的差异有显著意义(P<0.05);二组间肝纤维化四项指标值的差异有显著意义(均为P<0.05)。服药期间,未见严重药物不良反应。试验组一般副反应与对照组差异无显著性。结论强肝胶囊有减轻血吸虫病早期肝纤维化的作用,用药安全,可选择作为治疗血吸虫病早期肝纤维化的药物。     

晚期日本血吸虫病患者肝组织基质金属蛋白酶2和9的表达

目的研究基质金属蛋白酶2(MMP-2)、基质金属蛋白酶9(MMP-9)在晚期日本血吸虫病患者肝组织中的表达及意义。方法26例晚期日本血吸虫病患者肝活检标本和5例正常人肝标本行常规病理检查,用MMP-2、MMP-9和Ⅳ型胶原(G-Ⅳ)单克隆抗体进行免疫组织化学染色进行定量和定位研究。结果MMP-2主要表达在肝细胞浆、肝细胞膜和肝窦,肌成纤维细胞和血管内皮细胞也有表达。MMP-9主要表达在肝星状细胞、肝窦和肌成纤维细胞,偶见肝细胞浆和胆管上皮细胞表达。晚期日本血吸虫病患者肝组织MMP-2、MMP-9和G-Ⅳ的表达明显高于正常人(P<0.05),随着汇管区炎症活动度和肝纤维化程度的升高,MMP-2的表达也明显增强(P<0.01),MMP-9的表达无明显改变(P>0.05),C-Ⅳ表达与MMP-2呈同步关系。结论MMP-2与日本血吸虫病肝纤维化的发生、发展有关,MMP-9表达与日本血吸虫病肝纤维化的发生有关。     

己酮可可碱抗日本血吸虫病肝纤维化的研究

己酮可可碱(PTX)具有抗纤维化的作用.早期应用PTX可减轻肝脏损伤和炎症反应,且在治疗肝纤维化时不良反应很少.本研究通过检测PTX治疗前后血吸虫病肝纤维化小鼠肝脏转化生长因子β1(TGF β1),Ⅰ、Ⅲ型胶原,诱导型一氧化氮合酶(iNOS)的含量及血清肿瘤坏死因子(TNF) α,干扰素(IFN) γ,一氧化氮(NO)水平的变化,探讨PTX在抗日本血吸虫病肝纤维化的作用及机制.     

日本血吸虫病合并HBV和HCV感染血清肝纤维化指标的变化？…

目的：探讨ＨＢＶ和ＨＣＶ对日本血吸虫病肝纤维化的影响。方法；用放免和酶标法分别测定晚血，慢血和自然人群血清的ＨＢＳＡｇ和抗ＨＣＶ，分成ＨＢＳＡｇ阳性组，抗ＨＣＶ阳性线和双阴性组，用放免法和生化法测定其血清肝纤维化即透明质酸（ＨＡ）。层粘蛋白（ＬＮ）Ⅲ型前胶原（ＰＣⅢ）谷胱甘肽Ｓ转移酶（ＧＳＴ）。结果：晚血的肝纤维化和指标显著高于慢血，后者又显著高于自然人群，晚血的ＨＢｓＡｇ和抗－ＨＣＶ阳性组的ＨＡ     

慢性日本血吸虫病肝纤维化差异表达基因的生物信息学分析

目的 筛选慢性日本血吸虫病肝纤维化差异表达基因（differentially expressed genes, DEGs）,并对其功能进行分析。方法 从基因表达综合（Gene Expression Omnibus, GEO）数据库下载慢性日本血吸虫病肝纤维化患者测序表达谱数据集,利用R语言进行DEGs筛选,对其生物学功能进行基因本体论（Gene Ontology, GO）和京都基因和基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）富集分析并构建蛋白质-蛋白质相互作用（protein-protein interaction,PPI）网络,以筛选关键基因。结果 共鉴定出62个DEGs,其中12个下调表达基因、50个上调表达基因。GO富集分析显示,DEGs主要富集在脂肪酸、硫化合物、酰基辅酶A、硫酯代谢等116种生物学过程,线粒体基质、线粒体外膜、细胞器外膜等19种细胞组分及胰岛素样生长因子结合、氧化还原酶活性等7种分子功能。KEGG通路富集分析显示,DEGs与磷脂酰肌醇-3-激酶/丝苏氨酸蛋白激酶（phosphatidylinos...     

CD34 expression is associated with poor clinical outcome in patients with acute promyelocytic leukemia

This study investigated the clinical characteristics and prognostic relevance of CD34 expression in 47 patients with acute promyelocytic leukemia (APL), showing t(15;17) or PML/RARalpha. Ten (21.3%) of the APL patients were CD34(+). CD34 expression was associated with hypogranular morphology (P = 0.002) and hyperleukocytosis (P = 0.015). However, there were no statistically significant differences in age, sex, hemoglobin level, platelet count, or percentage of blasts between the CD34(+) and CD34(-) APL groups. Multiplex RT-PCR analysis showed that the L-form (BCR1) and S-form (BCR3) were correlated with CD34(-) APL and CD34(+) APL, respectively. Despite the lack of a difference in the complete remission rate, overall survival (OS) and disease-free survival (DFS) were significantly lower in the CD34(+) group than in the CD34(-) group (P = 0.012 and P = 0.0051, respectively). By multivariate analysis, the CD34(+) group showed a significant independent variable in DFS compared with the CD34(-) group, but this was not demonstrated for OS. In conclusion, CD34 expression in APL is a unique clinical feature associated with leukocytosis and atypical morphology with hypogranular pattern and is associated with a poor clinical outcome.     

Autologous CD34+ and CD133+ stem cells transplantation in patients with end stage liver disease

AIM:To assess the utility of an autologous CD34 + and CD133 + stem cells infusion as a possible therapeutic modality in patients with end-stage liver diseases.METHODS:One hundred and forty patients with endstage liver diseases were randomized into two groups.Group 1,comprising 90 patients,received granulocyte colony stimulating factor for five days followed by autologous CD34 + and CD133 + stem cell infusion in the portal vein.Group 2,comprising 50 patients,received regular liver treatment only and served a...     

Decreased L-selectin expression in CD34-positive cells from patients with chronic myelocytic leukaemia

Abnormal adhesive interaction between bone marrow stroma and progenitors, one of the causes of unregulated proliferation in chronic myelocytic leukaemia (CML), may be caused by some alterations in adhesion molecules on CML progenitors. We investigated the expression of adhesion molecules (CD44, VLA-5, VLA-4, LFA-1, ICAM-1, L-selectin and c-kit) on bone marrow CD34⁺⁺ cells from 16 CML patients by three-colour flow cytometry. The mean percentage of cells expressing L-selectin in the CD34⁺⁺CD38^{+  ∼  ++} fraction from untreated CML patients was significantly lower, and that in the CD34⁺⁺CD38⁻ fraction tended to be lower than that from normal controls. Among 11 CML patients treated with interferon-α (IFN-α), the mean percentage of the cells expressing L-selectin in the CD34⁺⁺CD38⁻ fraction from three patients with a low percentage of Ph¹(+) cells in bone marrow was significantly higher than that from five patients with a high percentage of Ph¹(+) cells. In addition, L-selectin expression rate was inversely correlated to the percentage of Ph¹(+) cells. There was no significant difference between the untreated patients and normal controls with regard to the expression rates of the other adhesion molecules in each CD34⁺⁺ fraction except LFA-1. These data suggest that decreased L-selectin expression in CML CD34⁺⁺ cells reflects one of the features of malignant CML progenitors.     

Characteristics of haemopoietic progenitor cells related to CD34 epitope class expression

Haemopoietic progenitor cells (HPCs) express the CD34 molecule, a heavily glycosylated transmembrane protein displaying three main classes of epitopes. The CD34 epitope class expression may vary between different subsets of HPCs. The aim of this study was to characterise the subsets of HPCs expressing CD34 class II and III epitopes. The cells were studied for coexpression of activation-, lineage- and adhesion-associated molecules, and their clonogenic ability and morphological features were examined. CD34+ HPCs expressing class III epitopes outnumbered those expressing class II. Class III expressing HPCs were enriched for CFU-GM and BFU-E and cells coexpressing CD13, CD33, c-kit and CD71 compared to class II expressing HPCs. CD34+ cells exclusively expressing class III epitopes uniformly displayed CD13 and CD33; they had a high clonogenic capacity and morphological characteristics of promyelocytes and myelocytes. The data show that class III epitopes are distributed more broadly on CD34+ HPCs than are class II epitopes, and that lack of class II epitopes is confined to CD34+ HPCs at a late stage of myeloid differentiation. The higher number of class III expressing HPCs coexpressing c-kit and CD71 suggests that these cells exhibit a higher proliferative or differential potential than do HPCs expressing class II epitopes.     

CD34+ cell selection is required to assess HOXA9 expression levels in patients with myelodysplastic syndrome

Overexpression of HOXA9 is linked to the molecular pathogenesis of acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS), conferring a poor prognosis. HOXA9 expression levels were analysed in the diagnostic bone marrow (BM) samples of 13 MDS patients. HOXA9 was expressed by CD34(+) BM cells at median levels 3.1-fold higher than in CD34(-) cells from the same patient and at median levels 4.3-fold higher than in CD34(+) cells from healthy donors. These results indicate that CD34(+) cell selection is required to accurately assess the expression levels of HOXA9 and related genes in the multipotential malignant progenitor cells of MDS patients.     

Angiogenesis in chronic myeloproliferative diseases detected by CD34 expression

Increased bone marrow angiogenesis estimated as bone marrow microvessel density (MVD), or as serum angiogenic factor levels and/or immunohistochemical expression of these factors in bone marrow biopsy has been demonstrated in a variety of hematological disorders including chronic myeloproliferative diseases (MPDs). The aim of this study was to investigate the MVD in 25 cases of myelofibrosis with myeloid metaplasia (MMM). MVD was estimated by CD34 immunohistochemical expression in bone marrow biopsies. A control group of 27 patients without bone marrow disease, eight cases of polycythemia vera (PV), 41 cases of essential thrombocythemia (ET) and nine cases of chronic myeloid leukemia (CML) were also studied. Moreover, in cases with MMM, MVD was correlated with clinical, laboratory, histological parameters and the outcome of the patients. Our study confirmed a significantly higher degree of angiogenesis in MMM, PV, ET and CML compared with controls (P < 0.001, P = 0.0007, P < 0.001 and P = 0.0008, respectively). Angiogenesis was higher in MMM than PV, ET and CML cases (P < 0.001, P < 0.001 and P = 0.008). Increased angiogenesis was correlated with hypercatabolic symptoms in MMM patients (P = 0.009). No correlation with other clinicopathological parameters or clinical outcome was found. However, definitive conclusions regarding the prognostic value of increased angiogenesis may require additional follow-up and a larger group of patients.     

Studies of P-glycoprotein in chronic myelogenous leukaemia patients: expression,activity and correlations with CD34 antigen

Over-expression of the P-glycoprotein (Pgp), transmembrane drug efflux pump, has been shown to cause multidrug resistance of tumour cells (MDR). To investigate the clinical significance of Pgp expression for chronic myeloid leukaemia (CML) diagnosis and monitoring we have studied 38 CML patients in various phases of the disease (chronic phase, CP; accelerated phase, AP; blast crisis, BC). Anti-Pgp monoclonal antibody UIC2 and FACScan analysis were used. Pgp functional activity was investigated by evaluation of verapamil influence upon rhodamine 123 efflux from the cells. Correlations between Pgp and CD34 expression were investigated. In CP, Pgp-expressing cells were found in 2/14 patients; in one of them Pgp proved to be non-functional. There were few Pgp-expressing cells in AP cases. The group of BC patients consisted of cases resistant to chemotherapy. This gave us the opportunity to consider whether drug resistance of BC CML patients is preferentially connected with Pgp-mediated MDR. 11/22 BC patients had 20% or more of Pgp-expressing blasts in the peripheral blood. In all four Pgp⁺ BC cases studied for Pgp activity this protein was functional. Only 4/22 BC patients demonstrated large (40% or more) fractions of Pgp⁺ blasts. Moreover, sequential studies of 11 BC CML patients during treatment revealed an increase in the number of Pgp-expressing cells in only two cases. This suggests that Pgp⁺ cells did not often accumulate in BC CML patients due to chemotherapy and are the cause of drug resistance in only a few cases. A positive correlation between Pgp and CD34 expression was found (r = 0.69; P = 0.0004). 3/22 BC CML patients had large fractions of both Pgp⁺ and CD34⁺ blasts in their peripheral blood. The BC CML patients with this immunophenotype of blast cells may represent a subtype of BC CML resistant to treatment due to Pgp over-expression.