干扰素联合丙种球蛋白治疗儿童传染性单核细胞增多症疗效分析

目的:探讨3种不同药物组合治疗儿童传染性单核细胞增多症的临床疗效。方法:64例传染性单核细胞增多症患儿分为3组,选用干扰素(ITF组)、干扰素 更昔洛韦(ITF GCV组)和干扰素 丙种球蛋白(ITF IVIG组)3种治疗方法,并将治疗效果分为近、远期疗效,将各组的年龄、发病时间、退热时间、咽峡炎时间、平均住院时间、治疗前后白细胞总数和丙氨酸氨基转氨酶的变化、淋巴结肿大的消退时间、治疗费用等数据应用SPSS13.0统计软件进行分析。结果:ITF IVIG组在退热时间、咽峡炎时间和住院费用方面与ITF组和ITF GCV组差异有显著性,在住院时间和淋巴结肿大时间上差异不显著。在近期治疗效果上,ITF IVIG组明显优于其他两组,但在远期疗效、白细胞总数和肝功能转氨酶方面差异无显著性。结论:干扰素 丙种球蛋白可以明显提高儿童传染性单核细胞增多症的近期治疗效果,对远期疗效和总体病程无明显优势。     

慢性肝炎新分类法用于丙型肝炎的病理诊断及干扰素-α2a的疗效考核

为验证慢性肝炎新分类对慢性丙型肝炎（ＣＨＣ）诊断的实用性和疗效考核中的价值，对临床和病理证实的６４例ＣＨＣ，按新分类法分级、分期，并分析其中１６例干扰素治疗后的组织学变化以及与ＡＬＴ变化和病毒血症的关系。结果表明６４例病变大多较轻，分级属Ｇ１～２的占７３４％，分期属Ｓ０～２的占８５９％，１６例经干扰素α２ａ治疗半年后多数病例显示有一定疗效，组织学活动性指数（ＨＡＩ）下降者１０例，纤维化分期降低８例，ＡＬＴ完全正常１０例，ＨＣＶＲＮＡ转阴或维持阴性的１１例。治疗后ＨＡＩ降幅较大的有：原有病变活动性高者、治疗后ＡＬＴ降至正常者、治疗前病毒血症阳性者。结果提示新分类法能确切反映病变状况，ＨＡＩ是疗效考核的敏感指标，并与临床指标基本相符。     

Differential regulation of glycosaminoglycan,fibronectin, and collagenase production in cultured human dermal fibroblasts by interferon-alpha,-beta,and-gamma

Summary In order to determine whether interferons (IFNs) play a universal role in terminating the fibrotic response by inhibiting other fibroblast functions in addition to growth and collagen production, we investigated the effect of human recombinant (hu-r) IFN-alpha,-beta, and-gamma on the glycosaminoglycan, fibronectin, and collagenase production of cultured human dermal fibroblasts. Our results show that shortterm (48 h) treatment of confluent fibroblast cultures with hu-r-IFN-alpha₂ and hu-r-IFN-beta-ser₁₇ causes a concentration (1 to 1×10⁵ U/ml)-dependent inhibition of glycosaminoglycan production, has no effect on fibronectin production, and markedly increases collagenase production. In contrast, hu-r-IFN-gamma not only causes a concentration-dependent increase in collagenase production but also increases both glycosaminoglycan and fibronectin production. These results demonstrate that IFNs differently regulate fibroblast functions rather than universally inhibit all functions, and show that IFN-alpha and-beta exhibit a broader antifibrotic spectrum that IFN-gamma.     

Differentiation therapy of human cancer: basic science and clinical applications

Current cancer therapies are highly toxic and often nonspecific. A potentially less toxic approach to treating this prevalent disease employs agents that modify cancer cell differentiation, termed ‘differentiation therapy.’ This approach is based on the tacit assumption that many neoplastic cell types exhibit reversible defects in differentiation, which upon appropriate treatment, results in tumor reprogramming and a concomitant loss in proliferative capacity and induction of terminal differentiation or apoptosis (programmed cell death). Laboratory studies that focus on elucidating mechanisms of action are demonstrating the effectiveness of ‘differentiation therapy,’ which is now beginning to show translational promise in the clinical setting.     

丙型肝炎的自身免疫现象——鉴别诊断和治疗原则

丙型肝炎病毒(HCV)感染和使用干扰素可诱导丙型肝炎患者产生一系列自身抗体,甚至发生自身免疫性疾病。干扰素诱发自身免疫性疾病后,单纯停用干扰素,自身免疫性疾病不能完全缓解,需要相应治疗,包括应用免疫抑制剂。为研究干扰素治疗丙型肝炎诱发自身免疫性肝炎(AIH)的临床特征,本文分析了日本仓敷医学中心胃肠、肝病和营养科1992～2008年接受干扰素治疗的1626例丙型肝炎患者,结果显示仅1例女性患者最终发展为AIH,予激素治疗后病情缓解。HCV RNA感染后机体可产生非器官特异性自身抗体,干扰素治疗本身亦可诱导自身抗体产生,这种伴发的自身免疫现象并非干扰素治疗的绝对禁忌证,但自身抗体滴度很高时,应慎重使用干扰素。     

干扰素致甲状腺功能异常1例

1.病例资料:患者男性,37岁,汉族,北京籍,教师.因"发现ALT升高5年,间断心悸1年余"就诊.患者5年前劳累后感觉乏力,检查结果显示:ALT 67 U/L、抗-HCV阳性.1年半前HCV RNA水平为2.8×10(5)拷贝/ml,并开始干扰素α-2b 3 MU/d治疗,未服用利巴韦林;治疗3个月时查HCV RNA低于检测限.     

An extremely rare case of delusional parasitosis in a chronic hepatitis C patient during pegylated interferon alpha-2b and ribavirin treatment

During treatment of chronic hepatitis C patients with interferon and ribavirin, a lot of side effects are described. Twenty-three percent to 44% of patients develop depression. A minority of patients evolve to psychosis. To the best of our knowledge, no cases of psychogenic parasitosis occurring during interferon therapy have been described in the literature. We present a 49-year-old woman who developed a delusional parasitosis during treatment with pegylated interferon alpha-2b weekly and ribavirin. She complained of seeing parasites and the larvae of fleas in her stools. This could not be confirmed by any technical examination. All the complaints disappeared after stopping pegylated interferon alpha-2b and reappeared after restarting it. She had a complete sustained viral response.     

Gadd45b and Gadd45g are important for anti‐tumor immune responses

An effective Th1 type cell‐mediated immune response against cancer cells is critical in limiting cancer progression. Gadd45b, a signaling molecule highly up‐regulated during Th1 type responses, is studied for its role in limiting tumor growth. Mouse B16 melanoma cells implanted into Gadd45b^?/? mice grew faster than those in WT or Gadd45b^+/? littermate controls. The defect of Gadd45b^?/? mice in tumor immunosurveillance was attributed to the reduced expression of IFN‐γ, granzyme B, and CCR5 in Gadd45b^?/? CD8⁺ T cells at the tumor site. Activation of p38 MAP kinase, but not ERK or JNK, by either TCR‐stimuli or IL‐12 and IL‐18 is diminished in Gadd45b^?/? CD8⁺ T cells, resulting in reduced production of IFN‐γ. In addition, mRNA of T‐bet and Eomes were reduced in Gadd45b^?/? CD8⁺ T cells, supporting a critical role of Gadd45b in shaping the Th1 fate. More importantly, the tumor vaccination, which is effective in WT mice, failed in Gadd45b/Gadd45g doubly deficient mice. Collectively, these data demonstrate that members of the Gadd45 gene family are important for anti‐tumor immune responses.     

Type I interferon receptor signalling is induced during demyelination while its function for myelin damage and repair is redundant

The type I interferons, interferon-beta and alpha (IFN-β, IFN-α), are widely used for the treatment of autoimmune demyelination in the central nervous system (CNS). Their effects on de- and remyelination through the broadly expressed type I IFN receptor (IFNAR), however, are highly speculative. In order to elucidate the role of endogenous type I interferons for myelin damage and recovery we induced toxic demyelination in the absence of IFNAR1. We demonstrate that IFNAR signalling was induced during acute demyelination since the cytokine IFN-β as well as the IFN-dependent genes IRF7, ISG15 and UBP43 were strongly upregulated. Myelin damage, astrocytic and microglia response, however, were not significantly reduced in the absence of IFNAR1. Furthermore, motor skills of IFNAR1-deficient animals during non-immune demyelination were unaltered. Finally, myelin recovery was found to be independent from endogenous IFNAR signalling, indicating a redundant role of this receptor for non-inflammatory myelin damage and repair.