应用免疫组化方法检测癌基因ras产物P21在胃癌及癌前组织的表达

目的:对胃癌及癌前组织ras族基因产物P21的表达进行观察,籍以探讨P21异常表达在胃癌友生中的作用。方法:对110例胃癌、32例肠型异型增生及311例胃粘膜肠化组织中的P21进行免疫组织化学染色,并按组织学和粘液染色结果将胃粘膜肠化分为Ⅰ、Ⅱ和Ⅲ型。结果:110例胃癌P21染色阳性45例,阳性率为40.9％,早期癌染色阳性率与中晚期相比无显著差别(P>0.05)。32例异型增生P21染色阳性率为21.9％。在不同类型肠化中,Ⅲ型肠化染色阳性率(23.3％)与Ⅰ型(82％)和Ⅱ型(6.7％)相比差别非常显著(P<0.01)。结论:P21表达异常在胃癌恶变中可能起重要作用,Ⅲ型肠化与胃癌的发生可能有密切关系。     

银染PCR—SSCP方法检测61例白血病P53基因点突变

用银染PCR－SSCP方法检测61例不同类型的白血病P53抗癌基因点突变，结果在26例淋巴细胞白血病中检测出2例有P53基因的点突变，在35例髓系白血病中检测出1例有P53基因的点突变。临床观察3例P53基因点突变患者对化疗药物不敏感，其中2例病程进展凶险。结果显示，P53抗癌基因点突变导致功能失活在白血病发病过程中起一定的作用，并可作为判断预后和化疗反应性的检测指标。     

大肠肿瘤癌基因蛋白产物同步检测的对比分析

对大肠肿瘤连续切片组织同步进行了Ｃ－ｍｙｃ．Ｐａｎ－ｒａｓ和Ｐ５３三种癌基因蛋白产物的检测，结果显示：癌基因ｍｙｃ，ｒａｓ和Ｐ５３阳性表达率在结肠腺瘤分别为６１、１％（４４／７２）、３７．５％（２７／７２和５．６％（４／７２），大肠泉癌分别为７２．９％（５１／７０）、５１．４％（３６／７０）和４０．０％（２８／７０），而正常粘膜则分别为２８．０％（７／２５）、４．０％（１／２５）和０。印戒细胞仅有     

骨髓细胞嗜银蛋白染色的临床意义

对８８例病人的骨髓细胞进行了Ａｇ－ＮＯＲ染色，结果表明非肿瘤性疾病与白血病末缓解两组间；白血病末缓解与白血病缓解组间；淋巴瘤组与非肿瘤性疾病组间均有非常显著性差异。提示Ａｇ－ＮＯＲ染色对骨髓细胞良，恶性疾病具有鉴别价值。，     

癌基因产物P21^ras与胃肠道肿瘤

p_(21)~(ras)是ras族癌基因H-ras、K-ras和N-ras所编码的一组密切相关的蛋白质,正常p_(21)~(pas)能与GTP 结合,有GTP 酶活性,能将GTP 水解成GDP,为调节细胞正常生长代谢所必需。p_(21)~(ras)的结构发生异常或超量表达时,能使正常细胞发生恶性变化。抗p_(21)~(ras)单克隆抗体的应用,为研究各种肿瘤组织中的p_(21)~(ras)提供了方便。本文对p_(21)~(ras)的结构与功能、活化机制、单克隆抗体的制备和种类,常用检测方法及其在胃肠道肿瘤组织中的表达和意义作了简要复习。     

恶性浆膜腔积液脱落细胞中P21 ras蛋白表达状况及其意义

目的:检测浆膜腔积液脱落细胞P21 ras蛋白表达状况,探讨其对恶性浆膜腔积液的诊断价值.方法:将新鲜浆膜腔积液离心后收集脱落细胞,取部分细胞涂片进行常规细胞学诊断,据此将积液分为良性与恶性两组.对余下脱落细胞作"标准化"处理,包括去除红细胞、多聚甲醛固定、调整细胞浓度、制备细胞涂片,然后进行P21 ras蛋白免疫化学染色(SP法).结果:共108例浆膜腔积液,恶性53例,良性55例.39例恶性积液P21 fas蛋白免疫化学染色阳性(73.6%),且多为强阳性或阳性;12例良性积液P21 ras蛋白染色阳性(21.8%),且多为弱阳性或阳性,两组间阳性率(χ2=29.02,P＜0.001)及阳性强度(Uc=6.786,P＜0.001)的差异均有显著性统计学意义.P21 ras蛋白免疫化学染色诊断恶性积液的敏感度为73.6%,特异度为78.2%,诊断符合率达75.9%.结论:浆膜腔积液中脱落细胞P21 ras蛋白免疫化学染色在肿瘤细胞多为阳性,良性细胞多为阴性,对恶性体腔积液的诊断有较大的价值.     

急性白血病骨髓细胞培养前后表面抗原的表达与正常人的比较分析

通过培养前后的白血病细胞与正常造血细胞的比较认为两者有本质性差异，前者ＣＤ＿３８（下同）明显升高，而ＣＤ＿３４、ＯＫＴ＿９明显下降；ＣＤ＿３、ＣＤ＿４、ＣＤ＿８培养前后白血病组则皆明显降低，因而认为ＣＤ＿３８是正常造血干细胞恶变的标志，代表了白血病克隆的消长。体外培养中虽然加入基因重组的ＧＭ－ＣＳＦ、ＩＬ－３、ＥＰＯ，白血病细胞仍不能沿正常途径分化，说明粒单细胞成熟阶段的ＦＰＭ、ＬＮ＿３６明显较正常为低。     

苯那普利对糖尿病大鼠肾组织细胞周期蛋白激酶抑制剂P21~(CIPI)蛋白表达的影响

目的：探讨苯那普利对糖尿病大鼠肾组织细胞周期蛋白激酶抑制剂Ｐ２１ ＣＩＰ１ 蛋白表达的影响。　方法：大鼠随机分单侧肾切除对照组（Ｃ 组） 、糖尿病组（ Ｄ 组） 及糖尿病苯那普利治疗组（ ＤＢ 组） 。１ 周后，应用免疫印迹（ Ｗｅｓｔｅｒｎ 杂交） 分析各组肾皮质Ｐ２１ＣＩＰＩ蛋白表达。血浆、肾皮、髓质血管紧张素转换酶（ＡＣＥ） 活性由荧光分光光度法测得。　结果：单侧肾切除糖尿病大鼠１ 周体重即明显下降（ Ｐ＜ ０－０５） ，肾重／ 体重即肾脏肥大指数却明显增加（ Ｐ＜ ０－０５） ，血浆ＡＣＥ 活性有所下降而肾皮质ＡＣＥ 活性却有所上升。Ｗｅｓｔｅｒｎ 杂交分析表明对照组肾皮质几乎没有Ｐ２１ＣＩＰ１ 蛋白表达，然而，糖尿病肾皮质Ｐ２１ ＣＩＰ１ 蛋白表达明显增加；苯那普利治疗１ 周对肾脏肥大有明显的抑制作用，对血浆、肾皮、髓质ＡＣＥ 活性抑制分别达８９－０ ％ 、７０－０ ％ 、７０－５ ％ ，对肾皮质Ｐ２１ ＣＩＰＩ蛋白表达抑制达６０－０ ％ 。结论：苯那普利对糖尿病肾脏肥大的抑制作用至少部分与Ｐ２１ ＣＩＰＩ蛋白表达降低有关，其确切机制尚有待于进一步研究     

Immunohistochemical Detection of Ras Oncogene p21 Product in Liver Cirrhosis and Hepatocellular Carcinoma

Expression of the ras oncogene p21 product by hepatocytes of cirrhotic liver with hepatocellular carcinoma (HCC) was examined immunohistochemically using mouse monoclonal antibody RAP-5. At the concentration of antibody used, histologically normal liver tissues were negative for p21 antigen, whereas hepatocytes of cirrhotic nodules from 80 of 92 HCC patients (87.4%), and 10 of 32 patients without HCC (59.4%) were positive. This difference was statistically significant (p less than 0.05). The incidence of p21 expression by hepatocytes was significantly higher in macronodular cirrhotic patients than in those with micronodular cirrhosis (p less than 0.05) and tended to be higher in those positive for hepatic hepatitis B virus markers than in those that were negative (p less than 0.1). All 16 patients with liver cell dysplasia, and 17 of 18 with adenomatous hyperplasias showed increased expression of p21 antigen. In HCC it was detected on tumor cells of 63 of 101 patients (62.4%). Characteristically, its expression in well-differentiated HCC was mild and uniformly diffuse, and in moderately differentiated tumors was markedly heterogeneous in both intensity and distribution, whereas no expression was observed in cells of poorly differentiated HCC. These observations suggest that elevated ras p21 antigen expression is important in the development of both cirrhotic nodules and HCC, but that after tumor development, its sustained elevation is no longer necessary for cell proliferation and progression through the grades of anaplasia.     

Bone Marrow Studies in Myelomatosis

The percentage of fat-cell areas in bone marrow particles from 22 patients with untreated myelomatosis was estimated. In only 1 patient was the mean fat cell area below 25 % of the bone marrow area measured. A negative correlation was found between the area of fat cells and plasma cells, indicating a displacement of the fat cell area by the plasma cells. 28 % of the patients had empty bone marrow deposits of iron. However, based on a normal iron saturation of S-transferrin and a normal sideroblast count in the bone marrow, the supply of iron to the erythropoiesis was considered sufficient. All patients but one had normoblastic bone marrows. Using a deoxyuridine suppression test in 10 patients, no biochemical defect could be demonstrated. To judge from the correlation coefficient a minor degree (9–14 %) of the variation in Hb values could be predicted from the cellularity in the bone marrow while a major degree (70 %) could be predicted from the renal glomerular filtration rate. The results do not support a displacement of blood-forming elements, iron deficiency, vitamin B₁₂ or folic acid deficiency to be of general significance in the pathogenesis of anaemia, but agrees with a causal relationship between anaemia and renal failure.     

Histomorphometrical Determination of Bone Marrow Cellularity in Iliac Crest Biopsies

The point-count principle is an exact method of bone marrow quantitation but fairly good correlation was found between quantitated and estimated values of the cellularity in iliac crest biopsies, although the latter values were significantly lower. No intraspecimen variation was found, but the cellularity in the individual biopsies varied considerably from field to field, indicating that quantitation and estimation on small samples obtained by aspiration may be misleading. The correlation between the values from undecalcified and decalcified sections was high, but decalcification of the biopsies resulted in an underestimation of the amount of haemopoietic tissue.     

Morphologic Studies of the Erythropoietic Part of the Bone Marrow in Myeloid Leukaemias

The erythropoietic part of the bone marrow has been morphologically analyzed in 147 patients with various forms of myeloid leukaemias and in 20 healthy controls. In all the patients the percentage of basophilic erythroblasts was abnormally high and correlated to elevated mitotic indices. Megaloblastic changes were found to be relatively common in the patients. All these findings are compatible with an ineffective erythropoiesis where the normal differentiation towards more mature erythroblasts becomes increasingly blocked during the course of the disease regardless of the type of myeloid leukaemia.     

Assessment of Bone Marrow and Splenic Erythropoiesis in Myelofibrosis

The iron uptake in bone marrow and spleen was measured in 29 patients with myelofibrosis using ⁵²Fe and quantitative scanning. In 10 patients, no iron uptake in the marrow could be observed and active erythropoiesis was extramedullary only. In the bone marrow of patients with myelofibrosis, the iron uptake per nucleated red cell was less than that observed in conditions without myelofibrosis or extramedullary erythropoiesis. Increasing splenic iron uptake was likely to be associated with a decreasing bone marrow iron uptake and was related to the size of the spleen. The data suggest that in myelofibrosis, the spleen dominates iron uptake through intense erythropoiesis and a high splenic blood flow, thus restraining iron supply to the bone marrow.     

骨髓干细胞动员治疗脑梗死

脑梗死时的神经细胞损伤以神经元死亡最为突出。骨髓干细胞动员是新兴的细胞治疗方法,利用细胞因子使主要位于骨髓中的干细胞进入外周血,并通过血液循环到达损伤组织,修复受损神经元。文章就骨髓干细胞动员、归巢和治疗机制的研究进展做了综述。     

47例骨髓穿刺干抽的临床及病理分析

作者分析该院发生的47例骨髓穿刺干抽的临床及病理改变,47例干抽占同期1319例骨髓穿刺的3.6％。根据骨髓细胞的密度和间质纤维增殖的程度,把干抽的原因分为4类:高细胞伴间质细胞增多19例(42.2％);间质细胞增多14例(1.1％);高细胞8例(17.8％)及低细胞4例(8.9％)。主要疾病为:急性淋巴细胞白血病(25.5％),急性非淋巴细胞白血病(17.0％),慢性白血病(14.9％),骨髓转移癌(10.6％),再障(6.4％),原发性骨髓纤维化(6.4％)。27例白血病占47例干抽的57.4％,其干抽原因与间质细胞增多和(或)高细胞性有关;骨髓转移癌的干抽与继发骨髓纤维化有关;再障的干抽与骨髓细胞显著减少有关。     

Regulation of Cobalamin and Folate Metabolism by Methionine in Human Bone Marrow Cultures

In cobalamin deficiency folate metabolism is disturbed. In the liver this deranged metabolism can be overcome by methionine, however, methionine failed to overcome this abnormality in bone marrow cultures from cobalamin deficient patients. In cobalamin deficient E. coli mutant bacteria, methionine under different conditions could either inhibit or potentiate the growth of the organism. This study was therefore initiated to test the effect of methionine, under different conditions, on bone marrow cultures. The defective DNA synthesis in megaloblastic bone marrow due to cobalamin deficiency could be corrected by the in vitro addition of low 0.27 μmol (40 μg) but not high 6.7 μmol (1 mg) amounts of methionine. This was measured by the ability of deoxyuridine to suppress the ³H-thymidine incorporation into DNA. The effect of methionine in facilitating de novo DNA synthesis is probably due to the catalytic action of SAM which activates cobalamin dependent methyltransferase enzyme thus potentiating the effect of cobalamin. In contrast high concentrations of methionine may inhibit this enzyme.     

Ki-67和P21在肾上腺皮质癌中的表达及意义

目的　探讨肾上腺皮质癌 (ACC)中Ki 67和P2 1的表达及其意义。方法　采用免疫组化SP法和图像分析技术对 8例正常肾上腺组织、2 0例肾上腺腺瘤 (ACA)、19例肾上腺皮质癌中Ki 67、P2 1进行检测。结果　Ki 67和P2 1的表达在肾上腺腺瘤与肾上腺皮质癌间差异均有统计学意义 (P <0 .0 1,P <0 .0 5 )。Ki 67的表达与肾上腺皮质癌分期、浸润或转移、2年生存情况相关(P <0 .0 1) ,与肿瘤大小无关 (P >0 .0 5 )。P2 1的表达与肾上腺皮质癌的大小、分期、浸润或转移、2年生存情况均无显著相关 (P >0 .0 5 )。结论　Ki 67和P2 1对肾上腺皮质良恶性肿瘤具有重要的鉴别诊断作用 ,Ki 67可作为判断肾上腺皮质癌预后不良的指标。     

自身骨髓移植在晚期恶性肿瘤治疗中的应用

本文报导我院1980～1991年6月因患各种晚期恶性肿瘤,主要是儿童恶性肿瘤患者50例,接受强化疗及自身骨髓移植治疗的临床小结。结果示(1)自身骨髓移植对治疗小儿恶性脑瘤、淋巴瘤、神经母细胞瘤等均有一定疗效,脑瘤组最明显;(2)脑瘤组在移植后需继续维持化疗3年左右,以防复发;(3)无论晚期淋巴瘤、神经母细胞瘤、急性白血病,在完全缓解期作移植,疗效好。(4)50例作自身移植者的结果提示自身骨髓移植对治疗晚期恶性肿瘤,是一种较安全、有效、值得采用的方法。