鼻腔淋巴瘤的病理类型及免疫表型与EB病毒的相关性

目的 探讨鼻腔淋巴瘤的类型、免疫表型及ＥＢＶ的关系。方法 选用Ｔ、Ｂ及ＮＤ淋巴细胞单克隆抗体,采用免疫组织化学方法标记２２例鼻腔淋巴瘤;用原位杂交法检测ＥＢＶ编码的ＲＮＡ（ＥＢＥＲ１／２）。结果 （１）Ｔ细胞来源占４５．４５％（１０／２２）,ＮＫ细胞来源占４５．４５％（１０／２２）,Ｂ细胞来源占９．０９％（２／２２）。（２）多形细胞淋巴瘤１７例（７７．３％）,单一形淋巴瘤５例（２２．７％）。（３）     

应用PCR和DNA酶免疫法对游离EB病毒进行检测和定量

本文介绍了通过检测血清中游离的ＥＢ病毒（ＥＢＶ）ＤＮＡ来定量分析ＥＢＶ感染情况。作者首先建立狨猴Ｂ９５－８细胞系进行预实验,然后采集２０例传染性单核细胞增多症患者和３０名健康献血员的外周血,用免疫荧光法检测血清中抗ＥＢＶ核壳抗原的ＩｇＧ和ＩｇＭ。用ＤＮＡ酶Ｉ降解Ｂ９５－８细胞系培养液上清中的ＤＮＡ后,再用ＱＩＡａｍｐ试剂盒提取所有培养液上清和标本血清中的ＥＢＶＤＮＡ。以这种ＤＮＡ为模板,用聚合酶链反应（ＰＣＲ）法扩增其内部重复序列中一长为２８８ｂｐ的特定片段,对扩增产物用ＤＮＡ酶免疫法检测其拷贝…     

表达结核杆菌不同分泌蛋白的DNA疫苗保护效力的差异

作者用质粒载体ｐＪＷ４３０３构建了分别表达结核杆菌分泌蛋白ＭＰＴ６４、Ａｇ８５Ｂ和ＥＳＡＴ－６的 ＤＮＡ疫苗 ＤＮＡ－６４、 ＤＮＡ－８５Ｂ和ＤＮＡ－Ｅ６。分别用上述ＤＮＡ疫苗免疫Ｃ５７Ｂ１／６小鼠,并以亲代ｐＪＷ４３０３作为阴性对照。免疫后４周用有毒力Ｈ３７ＲＶ株（约１００个活菌）通过气溶胶攻击,４周后取肺匀浆作活菌计数;在免疫后不同时间取血清用ＥＬＩＳＡ测特异性抗体;取部分小鼠淋巴结和脾细胞作淋巴细胞增殖试验及测细胞毒性Ｔ细胞（ＣＴＬ）应答和γ干扰素（ＩＦＮ－γ）分泌细胞。 结果显示,ＤＮＡ－６…     

43例鼻咽,鼻腔恶性淋巴瘤的临床病理及免疫表型研究

本文对遵义地区４３例鼻咽、鼻腔恶淋巴瘤的临床病理及免疫学表型进行了研究，结果显示：全部病例均为弥漫型，无１例滤泡型，组织学类型以多表细胞性淋巴瘤为主，共３３例（包括小细胞型１３例，中多形１５例，大多形５例），占７６．７％。用ＵＣＨＬ－１、ＣＤ２０和Ｍａｃ３８７等多单克隆抗体进行免疫表型研究。显示Ｔ细胞淋巴瘤３７例（８６％），Ｂ细胞淋巴瘤４例（９．３％），无１例组织细胞性淋巴瘤。鼻咽部Ｔ．Ｂ淋巴瘤比     

以DNA、痘苗病毒和蛋白免疫接种提呈HIV Env蛋白的新方法

重组ＤＮＡ、痘苗病毒载体（ＶＶ）作为人类免疫缺陷症病毒（ＨＩＶ）抗原的送递系统因其能同时诱导细胞免疫和体液免疫而受到重视,作者对表达ＨＩＶ包膜（Ｅｎｖ）蛋白的ＤＮＡ和ＶＶ载体（ＤＮＡ－Ｅｎｖ和ＶＶ－Ｅｎｖ）及纯化的Ｅｎｖ蛋白的免疫效果进行了检测。 将ＨＩＶ－ⅢＢ株的 ｇｐ１４０ Ｅｎｖ编码序列插入含有巨细胞病毒增强子／启动子的质粒中,用基因枪将包被于金粒上的重组质粒注入８～１２周龄的Ｃ５７ＢＬ／６小鼠腹部;或腹腔接种表达 ＨＩＶ－ⅢＢ株蛋白的重组 ＶＶ感染细胞的裂解物;纯化蛋白疫苗则由ｇｐ １２０（１…     

头颈部恶性肿瘤病人口咽部含漱液EBV-DNA检测

用多聚酶链式反应（Ｐｏｌｙｍｅｒａｓｅｃｈａｉｎｒｅａｃｔｉｏｎ，ＰＣＲ）方法对一组头颈部恶性肿瘤病人口咽部含漱液中的Ｅｐｓｔｅｉｎ－Ｂａｒ病毒（ＥＢＶ）ＤＮＡ进行了检测。结果表明：鼻咽癌、恶性肉芽肿和扁桃体恶性淋巴瘤病人全部阳性，其他如喉癌、鼻腔鼻窦癌、甲状腺癌等病人中也有部分阳性结果。肿瘤组病人中总阳性率为７４．４７％；对照组为鼻、咽、喉慢性炎症病人，仅１例结果阳性（７．１４％）。结果提示ＥＢＶ可能参与了这些癌肿的发病     

贵州地区非免疫缺陷相关性B细胞淋巴瘤与EB病毒的关系

目的 探讨非免疫缺陷相关性B细胞淋巴瘤与EB病毒的关系。方法 采用原位杂交、免疫组织化学方法分别检测63例贵州地区非免疫缺陷相关性B细胞淋巴瘤中的EBER1／2、LMP－1蛋白。结果 63例B细胞淋巴瘤中,6例EBER1／2（＋）（9．5％）,其中有4／13例上呼吸道淋巴瘤（30．8％）;仅有1／63例（1．6％）LMP－1（＋）。结论 非免疫缺陷相关性B细胞淋巴瘤与EB病毒的相关性小,其致瘤作用的发挥可能与机体的免疫状态有关。     

TGF-β对原代培养肝细胞及肝癌细胞BEL7401生长作用的影响

目的 研究转化生长因子－β（ＴＧＦ－β）对正常大鼠肝细胞和肝肿瘤细胞的影响。方法 分离和培养原代大鼠肝细胞,培养ＢＥＬ４０１肝癌细胞,通过测定细胞ＤＮＡ合成、细胞活性（ＭＴＴ）及碱性磷酸酶活性,研究ＴＧＦ－β对正常大鼠肝细胞和肝肿瘤细胞的影响方式及可能的作用途径。结果 实验发现,ＴＧＦ－β可以刺激ＢＥＬ７４０１肝癌细胞的增生,促进其ＤＮＡ合成,并增强其活性ＳＴＧＦ－β对原代培养肝细胞ＤＮＡ合成无明显影响,对其活性有明显的抑制作用。实验还发现,ＴＧＦ－β明显刺激ＢＥＬ７４０１肝癌细胞中的碱性磷酸酶增高,同时抑制原代培养肝细胞的碱性磷酸酶活性。结论ＴＧＦ－β对正常细胞和肝癌细胞ＢＥＬ７４０１的生长有不同的影响作用,这种结果可能是通过不同的细胞信号传导途径实现的。     

疫苗及其转染能力

病毒疫苗及重组ＤＮＡ疫苗可能含有残余的细胞ＤＮＡ,外源ＤＮＡ可被哺乳动物细胞吸收和表达。疫苗中残余细胞ＤＮＡ的转染能力决定了疫苗的安全性,因此,这种转染能否引起宿主基因损伤或缺失,能否激活致癌基因是人们普遍关心的问题。 作者用含编码氯霉毒乙酸转移酶（ＣＡＴ）的表达载体 ＰＣＡＴ３（ＰＤＮＡ） ３０μｇ／０．５ｍｌ,以磷酸钙和ＤＥＡＥ－葡聚糖法转染到人纤维肉瘤细胞ＳＷ６８４,ＣＡＴ表达量分别是３３３６．６和６４６．１ｐｇ／ｍｌ。同时选用９批疫苗,各加入 ３０μｇ ｐＣＡＴ３ ＤＮＡ,接种到ＳＷ６８４细胞…     

Effect of epidermal growth factor on cultured rat hepatocytes poisoned by CCl~4

研究表皮生长因子（ＥＧＦ）对四氯化碳（ＣＣｌ４）所致大鼠原代培养肝细胞损伤的作用．方法：丙氨酸转氨酶（ＡｌａＡＴ）和天门冬氨酸转氨酶（ＡｓｐＡＴ）活力及Ｋ＋浓度用自动生化分析仪测定．丙二醛（ＭＤＡ）用苯巴比土酸比色法测定．放射活力用液体闪烁测量仪测定．细胞病理用光学显微镜和电子显微镜检查．结果：ＥＧＦ显著降低ＡｌａＡＴ，ＡｓｐＡＴ及ＭＤＡ水平，增加中毒肝细胞ＲＮＡ和ＤＮＡ的合成，且Ｋ＋漏出与ＤＮＡ的合成呈正相关．细胞病理显示ＥＧＦ减轻ＣＣｌ４对肝细胞的毒性作用．结论：ＥＧＦ对ＣＣｌ４所致原代培养肝细胞损伤有拮抗作用，肝细胞内Ｋ＋转运是ＤＮＡ合成起信息传递的启动因子．     

77例T细胞非霍奇金淋巴瘤的临床病理特点和免疫表型分析

目的探讨T细胞非霍奇金淋巴瘤的临床病理特点和免疫表型。方法对77例T细胞非霍奇金淋巴瘤进行苏木素和伊红染色(HE)和免疫组织化学检查,按WHO 2008年《造血和淋巴组织肿瘤的病理学和遗传学》标准进行分类。结果 77例T细胞非霍奇金淋巴瘤中,鼻型结外NK/T细胞淋巴瘤32例(41.6%),非特异性外周T细胞淋巴瘤20例(26.0%),间变性大细胞淋巴瘤11例(14.3%),前驱T淋巴细胞淋巴瘤9例(11.7%)。结论 T细胞非霍奇金淋巴瘤中,最常发生的亚型是鼻型结外NK/T细胞淋巴瘤,其次为非特异性外周T细胞淋巴瘤、间变性大细胞淋巴瘤和前驱T淋巴细胞淋巴瘤。其中,鼻型结外NK/T细胞淋巴瘤预后较差,而间变性大细胞淋巴瘤预后相对较好。     

肠病型T细胞淋巴瘤(附6例报告)

目的探讨肠病型T细胞淋巴瘤的临床病理特征、免疫表型及鉴别诊断要点。方法对6例肠病型T细胞淋巴瘤复习其临床资料,并行病理学检查、免疫组化染色及结合文献进行分析。结果6例均诊断为非霍奇金淋巴瘤T细胞型,其中2例为中大细胞型,4例为小细胞型。结论肠道T细胞淋巴瘤较少见,尤其是中大细胞型T细胞淋巴瘤,其临床病理表现较特殊,预后差,可能与EB病毒密切相关,临床诊断较困难,其诊断和鉴别诊断主要依靠病理组织学及免疫组织化学。     

非霍奇金淋巴瘤100例病理形态和免疫表型的观察

目的 根据WHO(2001年)淋巴瘤的新分类,对贵州省部分以往诊断的非霍奇金淋巴瘤(Non-Hodgkin's Lymphoma)重新进行形态学和免疫表型研究并分类,以探讨新的WHO分类在我省淋巴瘤分类中的适应性.方法 应用组织形态学观察及免疫组织化学分析对100例以往诊断的恶性淋巴瘤组织重新诊断分型,并根据新的WHO分类进行分类和回顾性分析.结果 100例NHL,B-NHL55例(55%),T-NHL44例(44%),有1例未明确诊断(1%).根据新的WHO分类,在B-NHL中,以弥漫性大B细胞性淋巴瘤(DLBCL)居多,共27例(47.2%).CD20表达94.5%(52/55).未能进一步分类3例(5.5%).在T-NHL,以外周T细胞淋巴瘤(PTCL)居多,共17例(38.6%),其次NK/T细胞淋巴瘤(NK/TCL)13例(29.5%).CD45RO表达86.3%(38/44).单纯HE染色的诊断结果符合率达78%,结合免疫组化符合率达96%.非霍奇金淋巴瘤Ki-67增值指数平均率为73.7%.结论 在病理形态的基础上,结合免疫表型,非霍奇金淋巴瘤绝大多数可明确诊断.WHO关于非霍奇金淋巴瘤的新分类是较为统一而又明确的分类方案,具有较强的实用性.     

IgH/TCR基因重排与EB病毒原位杂交联合分析在淋巴瘤诊断中的应用

目的：探讨免疫球蛋白重链/T细胞受体（IgH/TCR）基因重排检测联合EB病毒（EBV）原位杂交在淋巴瘤诊断中的应用,分析EBV＋-B细胞淋巴瘤的细胞学及基因组学特征、鉴别诊断要点,以缩短诊断时间,减少误诊。方法采用IgH/TCR基因重排与EB原位杂交联合分析诊断EBV＋-B细胞淋巴瘤1例,分析其免疫组化特征、EBV原位杂交、基因重排结果。结果 EBV＋-B细胞淋巴瘤临床上主要表现为淋巴结增大,常伴骨髓和外周血浸润。淋巴结活检显示其结构破坏,淋巴滤泡减少,淋巴结高度增生性病变,可见轻至中度异型淋巴细胞,淋巴窦扩张,组织细胞增生。免疫组化证实EBV感染的细胞毒性B细胞构成病变主体;EBV原位杂交显示部分淋巴细胞核阳性;基因重排提示IgH、免疫球蛋白轻链（Igκ）基因发生克隆性重排,TCRγ无克隆性重排。结论 EBV＋-B细胞淋巴瘤从形态学上难以与伯基特淋巴瘤、慢性淋巴细胞白血病等淋巴瘤区分,早期诊断困难。联合应用IgH/TCR基因重排与EBV原位杂交技术对EBV＋-B细胞淋巴瘤的诊断有较高准确性。     

Bexarotene in the treatment of cutaneous T-cell lymphoma

Primary cutaneous T-cell lymphomas encompass a spectrum of non-Hodgkin's lymphomas that are characterised by clonal proliferation of skin-homing malignant T lymphocytes. Mycosis fungoides and the leukaemic variant Sézary syndrome, collectively referred to as cutaneous T-cell lymphomas, are the most common entities. No curative therapy exists and patients ultimately develop advanced or relapsed disease that is refractory to standard treatment options. Therefore, there is a great need for the development of novel emerging therapies. Bexarotene is the first synthetic nuclear retinoid X receptor-selective retinoid approved by the FDA for the treatment of refractory cutaneous T-cell lymphoma in all stages, as both an oral capsule and a topical gel formulation. Bexarotene was found to induce apoptosis in a variety of preclinical in vitro and in vivo models including cutaneous T-cell lymphoma cells, and has shown efficacy in two multi-centre, open-label Phase II - III clinical trials for early and advanced stages of cutaneous T-cell lymphoma in patients who have failed or were refractory to standard therapies. New insights into the immunomodulatory function of bexarotene have indicated opportunities for combined treatment with IFN-alpha, denileukin diftitox or phototherapy. This article reviews the biological properties, pharmacokinetics, clinical efficacy, safety and role of bexarotene in the treatment of cutaneous T-cell lymphoma.     

Novel virally targeted therapies of EBV-associated tumors

EBV is associated to the development of several malignancies of lymphoid and epithelial origin, including Burkitt's Lymphoma, post-transplant lymphoproliferative disorders, Hodgkin's disease, AIDS-associated lymphomas, NK/T cell lymphoma and Nasopharyngeal carcinoma. EBV genes play an essential role in the development of the malignant phenotype and therefore molecules interfering with the function of these genes may represent an essential tool to treat EBV-associated malignancies. Several strategies to inhibit virus-induced tumorigenesis have been developed including antiviral and antitumor molecules, gene therapy approaches, interference with epigenetic regulatory mechanisms, adoptive and active immunotherapeutic protocols. While gene therapy and epigenetic approaches gave inconsistent results, immunological therapies using ex vivo expanded autologous and allogenic cells specific for EBV have obtained promising results. The major challenge is now to improve the current knowledge on virus replication strategies and on the characteristics of protective immune response that may result in more effective therapeutic protocols.     

Bexarotene in the treatment of cutaneous T-cell lymphoma

Primary cutaneous T-cell lymphomas encompass a spectrum of non-Hodgkin’s lymphomas that are characterised by clonal proliferation of skin-homing malignant T lymphocytes. Mycosis fungoides and the leukaemic variant Sézary syndrome, collectively referred to as cutaneous T-cell lymphomas, are the most common entities. No curative therapy exists and patients ultimately develop advanced or relapsed disease that is refractory to standard treatment options. Therefore, there is a great need for the development of novel emerging therapies. Bexarotene is the first synthetic nuclear retinoid X receptor-selective retinoid approved by the FDA for the treatment of refractory cutaneous T-cell lymphoma in all stages, as both an oral capsule and a topical gel formulation. Bexarotene was found to induce apoptosis in a variety of preclinical in vitro and in vivo models including cutaneous T-cell lymphoma cells, and has shown efficacy in two multi-centre, open-label Phase II – III clinical trials for early and advanced stages of cutaneous T-cell lymphoma in patients who have failed or were refractory to standard therapies. New insights into the immunomodulatory function of bexarotene have indicated opportunities for combined treatment with IFN-α, denileukin diftitox or phototherapy. This article reviews the biological properties, pharmacokinetics, clinical efficacy, safety and role of bexarotene in the treatment of cutaneous T-cell lymphoma.     

Epstein-Barr virus (EBV). V. Incidence of EBV antibodies in patients with rheumatic diseases

Serum samples from 95 patients with rheumatoid arthritis, 24 patients with other various rheumatic diseases, 50 patients with diabetes mellitus, 34 patients with acute viral infections, 6 patients with infectious mononucleosis, 77 patients with lymphomas and leukemia and 110 blood donors and 24 healthy subjects as normal controls, respectively, were tested by indirect immunofluorescence (IF) reaction for the presence of specific antibodies against Epstein-Barr virus determined viral capsid antigen (anti-VCA) and Epstein-Barr active viral infection. The IF test carried out in acetone-fixed smears of EB-3 cell line revealed EB antibodies anti-VCA in 83.3% of infectious mononucleosis, 61.0% lymphomas and leukemia, 58.0% diabetic patients. The frequency of anti-VCA antibodies in rheumatic patients was 31.4%, and 3.6% and 25% in sera from blood donors and healthy subjects, respectively. Incidence of active EBV infection was 5.7% of rheumatic diseases, 17.7% of acute virus infections, 50.0% of infectious mononucleosis, and 31.1% of lymphomas and leukemia patients. Active EBV infection was not found out in blood donors (0/110) and healthy subjects (0/24) groups as control. Rheumatoid arthritis with or without rheumatoid factor patients had serological evidence of active EBV infection 6/26 and 4/26 respectively.     

Cell cycle and apoptosis deregulation in classical Hodgkin lymphomas

Classical Hodgkin lymphomas (cHL) have now been recognized as B-cell lymphomas with some exceptional cases of T-cell origin. In recent years, there has been accumulating evidence that Hodgkin and Reed-Sternberg (H/RS) cells, the presumed neoplastic-cell population in cHL, are characterized by a profound disturbance of the cell cycle and apoptosis regulation. The constitutive activation of the nuclear factor (NF)-kappaB pathway, which is considered to be involved in the proliferation and survival of H/RS cells. Moreover, substantial evidence that H/RS cells have defective cell cycle and apoptosis regulation has been provided by studies showing that these cells are characterized, in a large proportion of cases, by alterations of the p53, Rb and p27 tumor suppressor pathways, overexpression of cyclins involved in the G1/S and G2/M transition such as cyclins E, D2, D3, A and B1, overexpression of cyclin-dependent kinases such as CDK1, 2 and 6 and overexpression of anti-apoptotic proteins such as c-FLIP, bcl-xl, c-IAP2, X-linked I4P and survivin. Recent studies suggest that interleukin 13 (IL-13) is an important growth and survival factor in H/RS cells. Furthermore, the Epstein-Barr Virus (EBV), which is present in H/RS cells in about 30-50% of cHL, has been shown to affect the cell cycle and apoptosis regulation in cHL. The present review summarizes data with respect to the cell cycle and apoptosis deregulation in cHL.