丙型肝炎病毒基因分型及其与疾病程度、感染途径和干扰素疗效的关系

为探讨广州地区丙型肝炎病毒（ＨＣＶ）感染的基因型及其与疾病程度、感染途径和干扰素疗效的关系，作者应用分型ＰＣＲ技术对１５６例抗－ＨＣＶ阳性患者血清ＨＣＶＲＮＡ进行分型检测，并分析不同程度肝病及不同感染途径ＨＣＶ基因型分布，且对５１例经干扰素治疗的慢性丙肝作分型评价。结果１２４例ＨＣＶＲＮＡ阳性中，Ⅱ型占９０．３％（１１２例），Ⅲ型占８．１％（１０例），Ⅱ／Ⅲ型混合感染占１．６％（２例），未检出Ⅰ、Ⅳ型，说明广州地区ＨＣＶ感染以Ⅱ型为主；不同程度肝病及不同感染途径之间ＨＣＶ基因型构成比无明显差异，表明基因型与疾病严重程度及感染途径关系不大；干扰素治疗病例，ＨＣＶ－Ⅱ、Ⅲ型感染的总应答数、完全应答数及部分应答数分别为１８／４１，１１／４１，７／４１和８／１０，６／１０，２／１０，提示Ⅲ型感染疗效较好，ＨＣＶ基因型似可作为选择干扰素治疗病例及判断疗效的参考指标，但是由于观察的Ⅲ型病例数较少，需积累更多的资料才能作出更客观的结论。     

柳氮磺胺吡啶对溃疡性结肠炎患者血清IFN-γ、IL-4及黏膜炎症的影响

目的： 探讨柳氮磺胺吡啶（SASP）对溃疡性结肠炎（UC）患者血清干扰素（IFN）-γ、白细胞介素（IL-4)和黏膜炎症的影响。方法： 活动期中度UC患者50例，口服SASP 1 g，每日3次，共6周，应用ELISA法检测血清IFN-γ、IL-4，组织学检测黏膜炎症。结果： 患者治疗前血清IFN-γ为（31.6±4.3) ng/L，显著高于治疗后的(22.3±5.6) ng/L（P<0.05），治疗前IFN-γ明显高于对照组的(17.5±5.9) ng/L（P<0.01）；治疗前IL-4为(4.6±1.8) ng/L，显著低于治疗后的(8.9±2.0) ng/L（P<0.05），治疗前IL-4明显低于对照组的(10.9±2.7) ng/L（P<0.01）。治疗前后嗜酸性粒细胞浸润率分别为100.0%和90.0%（P<0.05），隐窝脓肿分别为48.0%和13.3%（P<0.01），黏膜组织学分级分别为（2.49±0.84）级和（1.31±0.75）级（P<0.01）。结论： SASP能明显逆转中度活动期UC患者的Th1和Th2细胞的失衡状态和UC炎症黏膜的隐窝脓肿，减少中性白细胞和嗜酸性粒细胞的浸润，从而促进炎症黏膜的愈合。     

Matrix protein mediated shutdown of host cell metabolism limits vesicular stomatitis virus-induced interferon-alpha responses to plasmacytoid dendritic cells

Upon infection with many different viruses, plasmacytoid dendritic cells (pDC) produce large amounts of type I interferon (IFN-/β). To address why upon vesicular stomatitis virus (VSV) infection pDC, but not conventional myeloid DC (mDC), are induced to produce IFN-, pDC and mDC were differentiated from bone marrow cells (BM-DC). Upon VSV infection BM-pDC produced IFN-, whereas BM-mDC did not. Notably, upon infection with VSV-M2, a VSV variant expressing a M51R mutant matrix (M) protein that showed a reduced sequestration of host cell metabolism, BM-pDC and BM-mDC mounted massive IFN- responses. Both DC subsets showed comparable RNA levels of retinoic acid inducible gene-I (RIG-I) and Toll-like receptor (TLR) 7 and were able to respond upon triggering with double-stranded RNA (dsRNA) or single-stranded RNA (ssRNA) analogs. Moreover, upon VSV-M2 infection IFN- production by both DC subsets was largely dependent on viral replication. Interestingly, upon virus infection BM-pDC, but not BM-mDC, up-regulated mRNA levels of nuclear export factors Nup96/98, probably reflecting cellular mechanisms to circumvent viral escape strategies. Collectively, these results indicated that cell types induced to produce IFN- upon viral infection are not primarily defined by cellular receptor configurations but rather by complex virus/host cell interactions.     

Human leukocyte interferon-α in cream,for the treatment of genital warts in asian women a placebo-controlled,double-blind study

The purpose of this double-blind, placebo-controlled study was to determine and compare the clinical efficacy and tolerance of human leukocyte -interferon (incorporated 2 × 10⁶ IU/g) in hydrophilic cream to cure genital warts. Preselected Asian female patients (n=150) aged 18–40 years (mean 22.5), with the clinical and biopsy-confirmed diagnosis of genital warts (mean 2.64), predominantly flat vaginal condylomas, were randomly allocated to 3 parallel groups. Each patient was given a coded tube containing 80 g placebo/active preparation with a graduated applicator. Patients were instructed to inject 6 g of the either alloted placebo/active cream deep into the vagina thrice a day for 3 consecutive days (group A) or 4 consecutive days (group B) per week, and if not cured the same treatment was extended to 3 more weeks (maximum 4 weeks active treatment). To assess the clinical efficacy patients were examined on a week-to-week basis. A total clearance of warts (biopsy-confirmed) was evaluated as a complete cure. Patients cured during the treatment were spared further treatment and were requested to visit us after 16 weeks for relapse control. As for the remaining patients, empty tubes were collected, and similarly coded replacement tubes were given for further treatment (in total 588 tubes were used). By the end of the treatment 57.2% lesions (227/397) were eliminated in all the groups: 48% patients in group A, 90% patients in group B, and 10% patients in placebo groups taken as completely cured. Of the 150 patients 128 (85.3%) did not complain of any drug-related adverse symptoms. Transitory increase in body temperature (mean 38.4°C), accompanied by headache (14.6%) and generalized itching (6.6%) were the most frequently reported side effects; however, treatment was well tolerated by all the patients, and there were no dropouts. Our findings indicate that clinical efficacy is dose dependent, that is, the results of group B were significantly superior to that of group A (P < 0.05). Of the 49.3% cured patients (74/150) followed up for 6 months (monthly basis) seven had a relapse, and none had reinfection. It is concluded that clinical efficacy of leukocyte interferon-a to cure genital warts is dose dependent. These results further support the view that leukocyte interferon-a incorporated in hydrophilic cream can be considered a reliable, safe, and home-based treatment to cure vulvar and vaginal warts.Abbreviation HPV human papillomavirus     

Biological response modifiers and infectious diseases: actual and potential therapeutic agents

Biological response modifiers (BRMs) are agents which can modify the immune response to cancer or invasion of the organism by infectious agents. An explosive appearance of new BRMs has resulted from the development of recombinant gene technology and the availability of monoclonal antibodies. Colony-stimulating factors first became available for the prevention of neutropenia but may also have a role in the treatment of infections. Interleukin-1 is being tested as a modular of hematopoiesis and may be useful as a helper factor for T- and B-cell function. Immunoglobulins are being used against viral and bacterial infections while interferons can prevent viral upper respiratory infections and suppress or irradicate some viral hepatitides. Other BRMs which show promise include chemical agents and traditional herbal medicines.     

Amelioration of Endotoxin-Induced Uveitis in Rabbit by Topical Administration of Tacrolimus Proglycosome Nano-Vesicles

This work was aimed to improve the efficacy of tacrolimus in the treatment of endotoxin-induced uveitis (EIU) using propylene glycol modified lipid vesicles termed as proglycosome nano-vesicles (PNVs). PNVs were prepared by modified film hydration method. Experimental uveitis in rabbit eye was induced by an intravitreal injection of 20 μL of the endotoxin solution containing 100 ng of lipopolysaccharide endotoxin. In vivo efficacy of PNVs was determined by studying clinical symptoms of uveitis using slit lamp examination and by quantitatively measuring levels of tumor necrosis factor-alpha, interleukin-6, leukocytes and total proteins in aqueous humor, 24 h after intravitreal injection of endotoxin. Comparison was made with healthy, untreated and tacrolimus solution treated eyes. PNVs developed were nano-sized, deformable and showed sustained release of tacrolimus over period of 12 h. In vivo results indicated statistically significant difference between the effects of PNVs in the treatment of EIU compared to tacrolimus. PNV treatment not only subsides clinical symptoms of uveitis but also prevented breakdown of blood aqueous barrier. Tacrolimus loaded PNVs are potential new topical treatment for uveitis.     

甲型流感病毒非结构蛋白1抑制干扰素抗病毒反应的研究进展

IFN-α/β是机体对抗外来病原体的第一道防线，其产生和后续激活的细胞信号转导可诱导具有抑制病毒感染和复制作用的IFN刺激基因的表达。然而，大多数病毒可通过表达一种或多种蛋白抵抗宿主细胞的抗病毒反应。流感病毒非结构蛋白1（nonstructural protein 1，NS1）作为多功能毒力因子，在流感病毒感染过程中起重要作用。此文概述了NS1的结构与功能及抑制IFN-α/β产生和抗病毒效应作用的机制，为研究流感病毒致病机理提供参考。     

The thymus in autoimmune Myasthenia Gravis: Paradigm for a tertiary lymphoid organ

In autoimmune Myasthenia Gravis (MG), a neuromuscular disease generally mediated by autoantibodies against the acetylcholine receptor (AChR), the muscle is the target organ of the autoimmune attack, while the thymus seems to be the primary production site of the autoantibodies. In the majority of patients with anti-AChR antibodies, it is characterized by the presence of germinal centers, which contain B cells that produce anti-AChR antibodies. In this review, we summarize recent results regarding neoangiogenic processes, cell infiltration and modified chemokine expression in the MG thymus, which are typical features of secondary lymphoid organs. The structural and functional changes in the MG thymus therefore allow us to declare it to be an archetype for tertiary lymphoid neogenesis providing optimal settings for the interaction between lymphocytes and antigen presenting cells in order to elicit an immune response. We further discuss factors that may have a key role in the transformation of the MG thymus into a tertiary lymphoid organ, such as IFN type I and dsRNA signaling. These factors could also be of importance in other autoimmune diseases, especially those characterized by tertiary lymphoid neogenesis.     

Sensitivity of Ph1+ CFU-GM to human recombinant interferon α and γ alone and in combination

Summary The in vitro effect of human recombinant interferon (IFN) alone and in combination were studied on granulomonocytic colony forming units (CFU-GM) from the peripheral blood of 10 Ph1+ chronic myeloid leukemia (CML) patients and from the marrow of 5 normal or non-leukemic subjects. - and -IFN alone determined a slight inhibition on colony growth with a preferential effect on pure macrophagic colonies. At maximum concentration (10⁴ U/ml) leukemic colony inhibition was 46±34% for IFN and 43±19% for IFN. Culture growth with + IFN in combination were significantly inhibited (up to 96±4%) with a concentration-related effect. Similar results were obtained with normal CFU-GM. The synergism that was found in vitro is probably relevant for the in vivo therapeutic effects of these compounds in CML and suggest that the combination is worth testing in vivo.This work was supported by CNR, Oncology Finalized Project, contract n. 8701169.44. and n. 8600603.44. and by AIRC