复方丹参注射液干扰素治疗乙肝后肝纤维化

目的探讨复方丹参注射液联合干扰素治疗慢性乙肝患者的疗效。方法110例慢性乙肝患者，按随机方法分成①对照组30例，应用普通保肝药物治疗，疗程6个月；②丹参组30例，应用复方丹参注射液（每ml含丹参、降香各1g）30ml加入10％葡萄糖溶液300ml中静脉注射1个月；③IFN组30例，应用IFN—α 3MU，隔日一次肌内注射，3个月；④联合组20例，应用复方丹参注射液30ml加10％葡萄糖溶液300ml静脉注射1个月，IFN-α 3MU，隔日一次肌内注射，3个月。丹参组，IFN组和联合组保肝药物治疗同对照组。四组病例在性别、年龄、病程，治疗前肝功能等方面均无统计学差异。治疗前检测肝功能，肝炎病毒标志，血清HA、IV—C、PCI—Ⅱ，部分病例进行肝穿病理检查。治疗开始后每月检测肝功能，3个月（治疗后）和6个月（随访时）时检测血清HA、IV—C、PCⅢ及乙肝病毒标志，治疗后1年行肝穿病理检查。结果治疗前四组患者血清HA、PCⅢ、IV—C水平无统计学差异；治疗后丹参组、IFN组、联合组血清HA、FCⅢ、IV—C水平较治疗前及对照组有不同程度的降低。结论复方丹参注射液联合IFN治疗可使血清HA、PCⅢ、IV—C有明显下降，肝组织病理改变明显改善，为目前有效的慢性乙肝治疗措施。     

γ—干扰素对过度增生的血管平滑肌细胞癌基因表达的抑制作用

本实验建立了兔腹主动脉球囊扩张（ＢＡ）动物模型。以地高辛标记的Ｃ一ｆｏｓ、Ｃ一ｍｙｃ，Ｎ一ｒａｓ癌基因探针进行ＢＡ术后血管段组织的原位杂交，以生物素标记的Ｃ一ｆｏｓ、ｃ一ｍｙｃ、Ｎ一ｒａｓ探针对经ＢＡ组织培养液刺激的、培养的血管平滑肌细胞（ＳＭＣ）进行细胞的原位杂交。结果显示：（１）ＢＡ术后再狭窄的血管段中ｃ一ｆｏｓ、ｃ一ｍｙｃ、Ｎ一ｒａｓ三种癌基因表达均增高，而且表达颗粒主要分布于粥样斑块中，中膜平滑肌层颗粒稀少。正常血管段无这三种癌基因表达。（２）经ＢＡ组织培养液刺激的ＳＭＣ胞浆中充满ｃ一ｆｏｓ，ｃ一ｍｙｃ癌基因表达颗粒。Ｎ一ｒａｓ癌基因表达主要位于细胞核膜部位。未给ＢＡ组织液刺激的ＳＭＣ未见以上癌基因表达。γ—干扰素可以部分抑制其表达。     

焦炉工人接触PAH水平与肺癌的关系

焦炉工人接触ＰＡＨ水平与肺癌的关系王溪鸿，马会良，杨玉萍（辽宁本溪钢铁公司劳动卫生研究所，１１７０２１）选择焦炉作业各工种工人两名，配戴个体采样器，测得一个工作班的接触浓度，连续测五个工作班，计算各工种每班平均接触浓度。采用高压液相色谱测定多环芳烃总...     

人白细胞干扰素诱导慢性乙型肝炎病人DNA损伤修复的探讨

应用不同浓度人白细胞干扰素处理10例慢性乙型肝炎病人外周血淋巴细胞,观察病人姐妹染色单体互换(SCE)频率的动力学变化.结果表明,人白细胞干扰素处理组SCE平均频率明显低于对照组,差异高度显著(P<0.01);慢性迁延性肝炎和慢性活动性肝炎处理组之间SCE平均频率无显著性差异;但人白细胞干扰素处理低浓度组SCE平均频率低于高浓度组,差异不显著(P>0.05).提示人白细胞干扰素具有诱导HBV损伤人体DNA的修复作用;大剂量人白细胞干扰素对HBV损伤人体DNA的修复未必有益.     

Remote abscess formation during interferon-α therapy for viral hepatitis

Abscess formation at the injection site is an unusual infectious complication of interferon- α (IFN- α ) treatment of chronic hepatitis C virus (HCV) infection, but remote abscess formation during IFN- α therapy is very rare. In the present communication, we report three cases of remote abscess formation detected among 68 patients with chronic viral hepatitis treated with IFN- α , and review the pertinent English literature. We believe that, as fever and constitutional symptoms are common side effects of IFN- α treatment, a high index of suspicion is indicated to exclude abscess formation in cases of unexplained fever during IFN- α therapy.     

Occurrence of thyroid autoimmunity in relapsing remitting multiple sclerosis patients undergoing interferon-β treatment

We analyzed the titer of antithyroid autoantibodies Abs) and thyroid function in 17 multiple sclerosis (MS) patients undergoing interferon-β (IFN-β) treatment and in 40 MS control patients. Basal evaluation revealed normal thyroid function in all patients. Abs were detected in 5 IFN-β-treated patients (29%) and in 4 MS control patients (10%). Our results indicate that IFN-β treatment may lead to thyroid autoimmunity. We therefore recommend periodic evaluations of antithyroid Abs and thyroid functionality in IFN-β-treated MS patients.     

Natural interferon enhances expression of placental alkaline phosphatase in human seminoma xenograft

The purpose of this study was to investigate the effect of natural interferon (IFN) on the expression of placental alkaline phosphatase (PLAP) in a human seminoma xenograft in severe combined immunodeficient mice. Mice were injected intramuscularly with 3 × 10⁵ U/mouse of IFN, twice a day, for five consecutive days. A significant increase in PLAP level of the xenografts followed IFN treatment. A radiolabeled anti-PLAP monoclonal antibody (MAb) was intravenously injected on the first day of IFN administration in order to determine if IFN has the potential to enhance the efficacy of an anti-PLAP MAb in the detection of seminoma. Enhanced retention of the anti-PLAP MAb was observed at 7 and 11 days after MAb administration. Thus, IFN treatment appears to have some effect on the efficacy of the anti-PLAP MAb in the detection of seminoma xenografts. Received: 26 September 1997 / Accepted: 23 April 1998     

Recombinant human interferonsα,β andγ reduce the antiproliferative action of cytarabine in K562 human myeloid leukaemia clonogenic cells

Summary The effects of recombinant human interferons , and (IFN) on the antiproliferative activity of cytarabine in K562 human myeloid leukaemia clonogenic cells were studied in an agar capillary microassay. The addition of IFN- did not affect the antiproliferative activity of cytarabine in K562 cultures treated with low concentrations of cytarabine (10–50 nM), whereas in those treated with high concentrations (100–150 nM) IFN increased the IC₅₀ of cytarabine on day 5 from 102 nM to 214 nM, i.e., cytarabine combined with IFN was about two-fold less potent than cytarabine alone. Similarly, low concentrations of IFN and IFN did not affect the antiproliferative activity of cytarabine on K562 colonies, but high concentrations of these two interferons: 4×10³ U/ml and 10⁴ U/ml respectively, increased the IC₅₀ of cytarabine on day 5 to 304 nM and to 316 nM respectively, i.e. cytarabine combined with IFN or IFN was about threefold less potent than cytarabine alone. The evaluation of the present negative interactions of interferons with cytarabine is warranted in fresh cells from myeloid leukaemia patients in primary culture.Abbreviation IFN interferon     

Preservation and redirection of HPV16E7-specific T cell receptors for immunotherapy of cervical cancer

Human papilloma virus (HPV) type 16 infections of the genital tract are associated with the development of cervical cancer (CxCa) in women. HPV16-derived oncoproteins E6 and E7 are expressed constitutively in these lesions and might therefore be attractive candidates for T-cell-mediated adoptive immunotherapy. However, the low precursor frequency of HPV16E7-specific T cells in patients and healthy donors hampers routine isolation of these cells for adoptive transfer. To overcome this problem, we have isolated T cell receptor (TCR) genes from four different HPV16E7-specific healthy donor and patient-derived human cytotoxic T lymphocyte (CTL) clones. We examined whether genetic engineering of peripheral blood-derived CD8+ T cells in order to express HPV16E711-20-specific TCRs is feasible for adoptive transfer purposes. Reporter cells (Jurkat/MA) carrying a transgenic TCR were shown to bind relevant but not irrelevant tetramers. Moreover, these TCR-transgenic Jurkat/MA cells showed reactivity towards relevant target cells, indicating proper functional activity of the TCRs isolated from already available T cell clones. We next introduced an HPV16E711-20-specific TCR into blood-derived, CD8+ recipient T cells. Transgenic CTL clones stained positive for tetramers presenting the relevant HPV16E711-20 epitope and biological activity of the TCR in transduced CTL was confirmed by lytic activity and by interferon (IFN)-gamma secretion upon antigen-specific stimulation. Importantly, we show recognition of the endogenously processed and HLA-A2 presented HPV16E711-20 CTL epitope by A9-TCR-transgenic T cells. Collectively, our data indicate that HPV16E7 TCR gene transfer is feasible as an alternative strategy to generate human HPV16E7-specific T cells for the treatment of patients suffering from cervical cancer and other HPV16-induced malignancies.     

一种新的土拨鼠α干扰素基因分型方法的建立及其意义

目的：建立新的土拨鼠α干扰素（IFN-α）基因分型方法，分析急性和慢性土拨鼠肝炎病毒（Woodchuck hepati-tis virus，WHV）感染的土拨鼠肝细胞中不同型别的IFN-α基因表达谱及其意义。方法：利用已知序列和基因型的土拨鼠IFN-α基因克隆质粒，建立基于土拨鼠IFN-α基因序列的限制性片段长度多态性的土拨鼠IFN-α基因分型方法。PolyIC体外刺激正常土拨鼠外周血单个核细胞（PBMC），调查正常土拨鼠PBMC受PolyIC刺激后IFN-α基因的表达谱。提取急性和慢性土拨鼠肝炎病毒感染的土拨鼠肝组织mRNA，RT-PCR扩增土拨鼠IFN-α基因，分子克隆后调查急性和慢性感染的土拨鼠肝细胞中IFN-α基因表达谱。结果：建立了土拨鼠IFN-α基因限制性片段长度多态性分型方法。急性和慢性感染的土拨鼠肝细胞中IFN-α基因的表达谱明显不同于正常动物的表达谱，假基因表达所占比例大。结论：新建立的土拨鼠IFN-α基因分型方法可用于分析土拨鼠不同组织中IFN-α的基因表达谱。