慢性粒细胞白血病的染色体变化

本文报道6例慢性粒细胞白血病的染色体变化,其中5例处于慢性期阶段.1例为急变期阶段。6例病人都有PH_1染色体,并伴有亚二倍体、超二倍体、多倍体。亦发现该病人中内复制的出现率很高,发现1例急变期患者有1个异常克隆核型。     

慢性粒细胞白血病的核型及其预后意义

目的 :分析细胞遗传学在慢性粒细胞白血病 (CGL)的诊断、疗效及其预后中的临床意义。方法 :对 116例采用骨髓细胞直接法和 (或 )短期 ( 2 4h)培养法制备染色体标本 ,采用R显带技术进行核型分析。结果 :在 116例CGL中 ,发现 110例Ph( +) ,在病程各期 (慢性期、加速期、急变期 )均出现 ,占 94.8%。 6例Ph( -) ,占 5 .17%。其中 96例Ph( +)细胞为 10 0 % ,占 87.2 %。 14例Ph( +)细胞为 41.6%～ 93 .1% ,占 12 .7% ,核型呈嵌合状态。 12例除Ph( +)外 ,还出现额外染色体改变 ,占 10 .9%。分别为双Ph ,+8,-Y ,-7及超二倍体 ( >46条 )。绝大部分患者经干扰素、羟基脲治疗后Ph( +)阳性率不变。结论 :染色体核型分析不仅有助于CGL的诊断和鉴别诊断。还是监测病情缓解或复发的重要指标。     

单纯性肾病综合征病儿红细胞免疫功能的变化

①目的探讨单纯性肾病综合征（ＳＮＳ）病儿红细胞免疫功能状态及其临床意义。②方法采用红细胞酵母菌花环法和单克隆抗体间接免疫荧光法，检测了２４例ＳＮＳ病儿活动期和缓解期及３０例健康儿童红细胞Ｃ３ｂ受体花环率（Ｅ－Ｃ３ｂＲＲ）和红细胞免疫复合物花环率（Ｅ－ＩＣＲ）及Ｔ细胞亚群的变化。③结果ＳＮＳ病儿活动期和缓解期Ｅ－Ｃ３ｂＲＲ皆显著低于对照组（ｔ＝８．１６，２．４７，Ｐ＜０．０１，０．０５），活动期明显低于缓解期（ｔ＝４．９５，Ｐ＜０．０１），而Ｅ－ＩＣＲ皆无异常；活动期Ｅ－Ｃ３ｂＲＲ降低与ＣＤ＋４细胞和ＣＤ＋４／ＣＤ＋８比值变化呈正相关（ｒ＝０．４８，０．５３，Ｐ＜０．０１），与ＣＤ＋８细胞变化呈负相关（ｒ＝－０．３６，Ｐ＜０．０５），但与激素治疗反应无相关性；缓解期有反复感染、病情反复或复发倾向者，Ｅ－Ｃ３ｂＲＲ较无上述特征者明显降低（ｔ＝２．３８，２．２５，Ｐ＜０．０５）。④结论ＳＮＳ病儿存在原发性红细胞免疫粘附活性降低，Ｅ－Ｃ３ｂＲＲ降低与其缓解期的易感倾向和病情反复或复发密切相关。     

老年肺心病患者急性发作期淋巴细胞凋亡与TNF、NO的相关性研究

目的研究老年慢性肺心痛(CPHD)患者不同病期外周血淋巴细胞(PBL)凋亡的变化，以及肿瘤坏死因子(TNF—α)与一氧化氮(NO)在发病中的作用，选取CPHD不同时期的患者30例与15例正常人进行比较，并探讨其临床意义。方法采用DNA断端标记法(TdT法)、ELISA法及griess法分别检测CPHD患者血淋巴细胞凋亡率的变化以及TNF、NO的水平。结果患者急性加重期的PBL凋亡率(33.12±7.80％)明显高于对照组8.32±1.43％(P<0.01)和缓解期8.77±2.17％(P<0.01)，TNF、NO的血浆浓度随病情变化而变化。结论老年CPHD患者PBL凋亡率TNF、NO与病情有关。     

新生儿缺氧缺血性脑病红细胞免疫黏附功能和T细胞活性的检测

①目的 探讨缺氧缺血性脑病（ＨＩＥ）病儿红细胞和Ｔ细胞免疫状态及其与临床相关性。②方法 应用酵母菌花环法、间接免疫荧光法检测ＨＩＥ病儿红细胞免疫附功能、Ｔ细胞亚群和Ｔ细胞白细胞介素－２受体（ＩＬ－２Ｒ）表达。③结果 ＨＩＥ组急性期红细胞Ｃ３ｂ受体花环率（Ｅ－Ｃ３ｂＲＲ）、ＣＤ４＾＋细胞、ＣＤ４＾＋／ＣＤ８＾＋细胞比值和Ｔ细胞ＩＬ－２Ｒ表达率明显低于对照组（ｔ＝４．２９～４．７５,Ｐ〈０．０１）,而     

Twelve Cases of Malignant Hematopathy Treated by Combined Therapy of Hematopoietic Stem Cell Transplantation and Chinese Herbal Medicine

Ｉｎｒｅｃｅｎｔｙｅａｒｓｔｈｅｈｅｍａｔｏｐｏｉｅｔｉｃｓｔｅｍｃｅｌｌｔｒａｎｓｐｌａｎｔａｔｉｏｎ（ＨＳＣＴ）ｄｅｖｅｌｏｐｅｄｒａｐｉｄ ｌｙ， ｐａｒｔｉｃｕｌａｒｌｙｔｈｅａｕｔｏ ｐｅｒｉｐｈｅｒａｌｂｌｏｏｄｈｅｍａｔｏｐｏｉｅｔｉｃｓｔｅｍ     

白血病MICM分型的临床和实验研究

从形态学、免疫学、细胞遗传学及分子生物学特性（MICM）探讨白血病与临床疗效的关系,用骨髓细胞形态及组织化学染色分析作FAB分型诊断;流式细胞术（FCM）单克隆抗体直接免疫标记技术检测白血病细胞分化抗原,短期培养法与直接法G显带染色体组型分析。双色荧光原位杂交技术检测bcr/abl融合基因,结果：共检测出异常抗原表达急性白血病7例,47例FAB分型的急性髓细胞性白血病（AML）中5例伴有淋系相关抗原表达。15例FAB分型的急性淋巴细胞性白血病（ALL）中2例伴有髓系相关抗原表达,2例ALL呈T,B相关抗原混合表达。急性白血病中检出46,XY,t(8;21）等染色体畸变和bcr/abl融合基因,20例慢性髓细胞性白血病（CML）中Ph染色体阳性16例,7例伴有复杂染色体核型变异,5例检出bcr/abl融合基因,Ph染色体阴性的CML中,1例检测出bcr/abl融合基因,3例为夏杂染色体核型变异。伴有异常抗原表达的急性白血病化疗一疗程完全缓解（CR）率和二疗程总CR率均低于呈单系相关抗原表达的急性白血病（P＜0.05）,伴复杂核型变异的CML急变时间短于Ph阳性的CML（P＜0.05）,结论：白血病的MICM分型与临床疗效密切相关。     

着色性干皮病皮肤成纤维细胞系(XP4SH)的建立及其生物学特性

着色性干皮病是先天性DNA修复功能缺陷的常染色体隐性遗传疾病。是研究人类DNA修复系统与肿瘤发生机理的理想实验模型。本文报告的XP4SH细胞系来源于XP患者皮肤,经体外培养表现为成纤维细胞的形态和生长特性,染色体众数为2n=46,双着丝粒染色体为其畸变的特征,经紫外线诱发的SCE率显著增高,而UDS水平则明显低下,细胞融合基因互补分析证实该细胞系归属于A互补群。     

婴幼儿急性呼吸道和肠道病毒感染染色体畸变率及SCE频率的探讨

本文研究了急性呼吸道和肠道病毒感染婴幼儿的染色体畸变率与SCE频率。初步探讨了病毒感染与染色体畸变率及SCE频率的关系。实验结果表明,病毒感染后染色体畸变率及SCE频率明显增加,与正常婴幼儿比较有非常显著差异。染色体畸变率与SCE频率之间不相关,r=-0.222。不同病毒感染不同个体所引起的染色体畸变类型不同,SCE频率变化也不同。     

Chromosome Studies in Leukemia

This review discusses the significance of chromosomal abnormalities found in leukemia with the bias of belief that these have a primary role or are the mechanism of action of leukemogenic agents. The Philadelphia chromosome (Ph¹) is present in marrow cells examined without culture at any stage of most patients with chronic granulocytic leukemia (CGL). the presence of this chromosome is of diagnostic and prognostic value.

Varied chromosomal abnormalities have been found in acute leukemia. Each abnormality, which may be unique, is absent in remission, found again at relapse and is seldom changed by therapy. Abnormalities may be of number of chromosomes (aneuploid) or structural rearrangements resulting in “marker” chromosomes, Ranges of abnormal numbers of chromosomes, when present, usually have related patterns which suggest origin of several cell types from one initial cell. Cells from patients with increased risk of leukemia owing to genetic factors have a high incidence of chromosome breakage and structural rearrangements suggesting a mechanism for production of clones of abnormal, possibly leukemic, cells.

     

系统性红斑狼疮儿童外周血淋巴细胞凋亡的初步研究

①目的　探讨系统性红斑狼疮 (SLE)儿童外周血淋巴细胞凋亡特性及其与病情和部分免疫指标的相关性。②方法　应用形态法、间接免疫荧光法和免疫金斑法 ,检测 1 8例SLE病儿和 1 5名健康儿童外周血淋巴细胞凋亡率、T淋巴细胞亚群、CD+2 5细胞百分率和抗ds DNA抗体。③结果　培养前及培养 48h ,SLE病儿组外周血淋巴细胞凋亡率均显著低于正常对照组 (t=2 .363 ,2 .954 ,P <0 .0 5 ,0 .0 1 ) ;培养 48h ,活动期病儿外周血淋巴细胞凋亡率明显低于稳定期病儿 (t=2 .2 94,P <0 .0 5) ,抗ds DNA抗体阳性组外周血淋巴细胞凋亡率显著低于抗ds DNA抗体阴性组 (t=2 .92 8,P <0 .0 1 ) ,SLE病儿外周血淋巴细胞凋亡率与CD+4 细胞百分率、CD+4 CD+8细胞比值和CD+2 5细胞百分率皆呈负相关 (r=- 0 .49～ - 0 .59,P <0 .0 1 )。④结论　SLE病儿外周血淋巴细胞凋亡减少 ,此与病儿细胞和体液免疫功能紊乱关系密切     

STI571治疗慢性期慢性粒细胞白血病的初步结果分析

OBJECTIVE: To compare the therapeutic effects of STI 571 in treating Philadelphia chromosome (Ph)-positive patients with chronic-phase and acceleration phase chronic myeloid leukemia (CML-CP and CML-AP, respectively). METHODS: A total of 19 CML patients with Ph chromosome and/or fluorescence in situ hybridization (FISH)-bcr/abl fusion gene positivity rates over 90% and a median age of 38 years were recruited in this study, 12 of whom had previously failed to respond to interferon-alpha. Five of the 19 patients were in accelerated phase and 14 in chronic phase, 9 of the latter patient group in early stage of CML-CP (within 1 year since diagnosis) and 5 in advanced stage (3-6 years since diagnosis). All the patients were given oral STI 571 at the dose of 300-500 mg/d for a median treatment course of 5 months, and the 5 patients with CML-AP also received homoharringtonine at dose of 1-2 mg/d for an average of 1.5 treatment cycles (7-14 d for a complete treatment cycle). The Ph chromosome and the FISH-bcr/abl were analysed again 3 months after the treatment. RESULTS: STI 571 induced 100% complete hematological remission (CHR) and 79% major cytogenetic responses (MCR) in these patients. The complete cytogenetic remission (CCR) rates of CML-AP patients and CML-CP patients in advanced stage were lower than that of CML- CP patients in early stage (0% and 40% vs 88.9%). CONCLUSION: STI 571 can achieve high rate of CHR and MCR in CML-CP patients, especially in those in early stage of the disease.     

脑血栓病人血浆内皮素水平24h动态检测

①目的探讨脑血栓急性期病人血浆内皮素（ＥＴ）水平２４ｈ内动态变化规律及其与发病的关系。②方法采用放射免疫测定法测定了３２例脑血栓病人和２０例健康人２：００，８：００，１４：００，２０：００时血浆ＥＴ水平的变化。③结果脑血栓病人昼夜血浆ＥＴ水平明显增高，与对照组比较差异均有极显著性（ｔ＝９．６４－１０．３３，Ｐ均＜０．００１），且在２４ｈ内２：００ＥＴ水平最低，８：００最高，两者比较差异有显著性（ｔ＝３．２２，Ｐ＜０．０ｌ）。有高血压和糖尿病病史的脑血栓病人２４ｈ的ＥＴ水平，均较无高血压、糖尿病病史者显著增高（ｔ＝２．１１－５．１７，Ｐ＜０．０５，０．０１）。④结论脑血栓急性期病人血浆ＥＴ水平２４ｈ内有早晨高和晚上低的节律性变化，其变化与脑血栓发病早晨为高发时间的现象一致。     

慢性粒细胞白血病骨髓组织学变异的探讨

本文报道16例慢性粒细胞白血病(CGL)骨髓活检组织学变异的结果,其中CGL慢性期初治6例,复治4例;CGL急变4例和完全缓解2例。各期骨髓组织学变化与细胞成分和造血细胞过度增生有关。急变期可出现骨小梁紊乱、水肿和坏死等。骨髓细胞学检查2例完全缓解,骨髓组织学检查仅1例完全缓解。纤维组织增生在各期均可发生,完全缓解时似可恢复正常,增生是病情进展和预后不良的指征。     

白血病患者血清铜、锌的变化

本文报道57例白血病血清铜,锌含量的测定结果。白血病治疗前血清铜升高,铜/锌值增大;治疗后,病情缓解者下降,未缓解者则更高。血清锌在治疗前后无何差异。急性淋巴细胞性白血病骨髓中白血病细胞百分数与血清铜浓度呈正相关。检测血清铜,锌对白血病疗效的预测及判断预后有一定意义。     

STUDY OF GIANT GROUP A MARKER CHROMOSOME IN SEVERAL BURKITT'S LYMPHOMA AND LYMPHOBLASTOID CELL LINES WITH EPSTEIN-BARR VIRUS FROM DIFFERENT ORIGINS

Several Burkitt's lymphoma and lymphobla- stoid cell lines with Epstein-Barr virus derived from different origins have been investigated cytogenetically. Giant group A marker chromosome was detected only in three lymphoblastoid cell lines from nasopharyngeal carcinoma (NPC'). With the exception of the HS2-1B lymphoblastoid cell line derived from a normal donor, the giant group A marker chromosome could not be found in the cell lines from the other sources, including P3HR-l, B95-8, Raji and lymphoblastoid cell lines from tonsil and so on. The results suggest that the giant group A marker chromosome might be associated with NPC. It has been proved by G-banding technic that this giant submetacentric group A chromo- some was formed by the translocation of the short arm of chromosome 3, breaking at the point near to or even involving its centromere, to the distal light band region of the long arm of chromosome l, namely t (1;3) (lp ter ->lq 44:: 3p11+3p ter) and t (1;3) Qp ter+lq 44::3q2b 3p ter). The occurrence rate of the marker chromo- some was only 6.670 half a year after CNL8 cell line was established; 82.0'70 after two years; and 100'/o after five years. The occurrence rate of the marker chromosome was 32To half a year after the NPC80 cell line had been established, and 72a/o after three years. Increase in the oc- currence rate of the marker chromosome in these cell lines was clearly paralleled to the time of the cell lines culture in vitro. In addition, the occurrence rate of the marker chromosome was not the same in differ- ent cell lines. It was only 6.670 half a year after CNL8 cell line was established, while it was 32% for NPC 80 and 63.3'70 for CNL5.     

SISTER CHROMATID EXCHANGE AND CELL CYCLE IN PERIPHERAL LYMPHOCYTES IN PATIENTS WITH ACUTE LEUKEMIA

Sister chromatid exchange (SCE) frequencies and cell cycle of peripheral blood lymphocytes in 49 cases of acute leukemia (36 cases of acute non-lymphocytic leukemia (ANLL), 13 cases of acute lymphocytic leukemia (ALL) and lI normal controls were studied. Increase of SCE frequencies was found in patients prior to treatment, and in those who were not in remission or those who were in relapse. For those who had attained their first complete remission within 6 months the SCE rate had decreased to a certain degree but did not return to the normal level. In 2 long-term survivors of acute myclocytic Ieukemia (AML) of 9.5 and 4 yc_*rs, vilzose treatment had been discontinued for more than l year, the SCE frequen cies were all within the normal limits. In cases of preleukemia the SCE frequencies were high. This finding may be of significance as a parameter for the disease process, diagnosis, therapeutic effecr and prognosis. Our observations indicated that the prolongation of cell cycle corresponds to the elevation of SCE and supports the hypothesis that the cell kinetics of Ieukemic cells of peripheral lymphocyte is similar to the cells in the bone marrow. After remission, the cell cycle may return to normal, re- flecting the relationship between therapeutic effect and cell proliferation. The increase of SCE frequen cies and the prolongation of cell cycle were more obvious in ALL than in ANLL, probably due to the increase of T-cell division of ALL under phytohemag- glutinin (PHA) stimulation.     

Application of autologous peripheral blood stem cell transplantation in children with malignant tumor

Objective To investigate if low dose total body irradiation (TBI, 6.0-9.0 Gy) combined with intensified chemotherapy followed by autologous peripheral blood stem cell transplantation results in better survival in children with refractory leukemia or solid tumors. Methods Twenty-one children with malignant tumors were included in this study.There w ere 14 males and 7 females aged 3.5-12 years.Underlying disease included high -risk acute lymphoblastic leukemia (ALL, CR(1) in 3 children and CR(2) in 5 ch ildren), acute myeloblastic leukemia (AML, 9 children), non-Hodgkin’s lymphoma stage Ⅳ ( 2 children), and neuroblastoma stage Ⅳ (2 children).The peripheral hematopoi etic stem cells were collected six to eleven months after complete response, mob ilized with high dose chemotherapy alone or combined with GM-CSF or G-CSF.Th e conditioning regimen consisted of chemotherapy with two to three combinations of the following drugs: cyclophosphamide, arabinosylcytosine, McNU, etopside, an d Idarubicin on the basis ofTBI (6.0-9.0 Gy).A mean of (1.8±0.5) ×10(8)/kg autologous mononuclear cells were transplanted.The patients were followed up after transplantation. Results Severe bone marrow suppression occurred in all patients around day +7.Peripher al white blood cell count decreased to 0 in all patients at day +4.8±2.9, and platelet count decreased to less than 20×10(9)/L at day +9.0±2.6.Succ essful engraftment was achieved in 21 patients, but four died of infection at da y +17, +20, +31 and +67, respectively.Recovery of white blood cell (WBC) to 10×10(9)/L, absolute neutrophil count to 0.5×10(9)/L, platelet count to 20 ×10(9)/L occurred on 21±12, 26±13, and 27±10 days, respectively.During the follow up period, three patients relapsed at +5 months, +1.5 years, and +2 yea rs 10 months, respectively.One patient died of intracranial hemorrhage at +8 m onths.Thirteen patients had event-free survival for 2-12 years, with a mean o f 6.7±3.4 years.Conclusion Our preliminary data suggest that myeloablative therapy with low dose TBI (6.0 -9.0 Gy) combined with intensified chemotherapy followed by autologous periphe ral blood stem cell transplantation might be associated with favorable results i n children with refractory leukemia or solid tumors.     

Modified conditioning regimen busulfan-cyclophosphamide followed by allogeneic stem cell transplantation in patients with multiple myeloma

Background Allogeneic stem cell transplantation is a potential curative approach in patients with multiple myeloma. The very high transplant related mortality associated with standard allogeneic stem cell transplantation is currently the major limitation to wider use of this potentially curative treatment modality. The challenge for clinical investigators is to reduce the incidence of post-transplant complications for patients receiving autologous hematopoietic stem cell transplantion for multiple myeloma. In this study the toxicity and efficacy of modified myeloablative conditioning regimen followed by allogeneic stem cell transplantation was investigated in patients with multiple myeloma. Methods The conditioning regimen consisted of hydroxyurea, cytarabine, busulfan, cyclophosphamide, and semustine. Ten patients underwent allogeneic transplantation among them hydroxyurea （40 mg/kg） was administered twice on day -10 and cytarabine （2 g/ms） was given on day -9, busulfan was administered orally in four divided doses daily for 3 days （days -8 to -6）. The dose of busulfan was 12 mg/kg in the protocol followed by cyclophosphamide intravenously over 1 hour on days -5 and -4 （1.8 g/m^2）, and with semustine （Me-CCNU） 250 mg/m^2 on day -3. Results Chimerism data were available on all patients and all patients achieved full donor chimerism without graft failure. Six patients had not acute graft-versus-host disease （GVHD, 36.4%; 95% CI： 13.9%-38.6%）. Two patients （18.2%） developed grade Ⅰ acute GVHD （95% CI： 10.9%-35.9%） and grade Ⅱ acute GVHD occurred in one patient （9.1%; 95% Cl. 8.4%-32.3%）. Severe grade IVa GVHD was seen in one patient, who died from acute GVHD. The incidence of chronic GVHD was 22.2% （95% Cl： 11.7%-36.7%）, among them one died of severe grade IV GVHD and one developed multiorgan failure on day ＋170; the treatment-related mortality was 22.0% （95% Cl： 10.3%-34.1%）. The overall 4-year survival rate was 67.8% （95% Cl： 16.3%-46.7%）. The estimated 4-year progression-free survival rate was 58.5% （95% CI： 13.7%-41.8%）. The 4-year complete remission was 72.7% （95% CI： 27.8%-49.6%）. One patient relapsed after 4 months and achived the complete remission after receiving the donor lymphocyte infusion. Conclusions Modified conditioning regimen busulfan-cyclophosphamide with peripheral blood stem cells＋bone marrow cells transplantation result in a low incidence of severe GVHD with a relatively low treatment-related mortality, high complete remission rates and a long-term survival.     

哮喘患者外周血调节性T细胞和Th17细胞数量及其转录因子的变化

[摘要] 目的： 观察哮喘患者外周血CD4+CD25+Foxp3+、CD4+IL-17+细胞的百分比和Foxp3、白介素-17(IL-17)、RORγt mRNA的表达水平的变化与哮喘发病的关系。方法： 分别取23例哮喘缓解期患者、25例哮喘急性发作期患者和20例健康人（对照组）的外周血单个核细胞（PBMC）,免疫磁珠阴选CD4+T细胞,采用Foxp3、IL-17胞内染色的方法,通过流式细胞术检测CD4+CD25+Foxp3+以及CD4+IL-17+细胞的百分比,应用RT-PCR检测Foxp3、IL-17、RORγt mRNA水平。结果： 免疫磁珠阴选CD4+T细胞纯度达90％以上。急性发作组患者外周血CD4+CD25+Foxp3+细胞百分比以及Foxp3 mRNA水平较对照组和缓解组明显降低（P＜0.01）,而缓解组和对照组比较,差异无统计学意义（P＞0.05）;急性发作组CD4+IL-17+细胞比例以及IL-17、RORγt mRNA表达较对照组和缓解组明显增高（P＜0.01）,而缓解组亦明显高于对照组（P＜0.05）。结论： Treg/Th17失衡可能和哮喘发病密切相关。