Inhibition of hepatitis B virus DNA replicative intermediate forms by recombinant interferon-γ

AIM: To evaluate the in vitro anti-HBV activity of recombinant human IFN-γ, alone and in combination with lamivudine. METHODS: A recombinant baculovirus-HBV/HepG2 culture system was developed which could support productive HBV infection in vitro. Expression of HBsAg and HBeAg in infected HepG2 culture medium was detected by commercial enzyme immunoassays. HBV DNA replication intermediates were detected in infected cells by Southern hybridization and viral DNA load was determined by dot hybridization. RESULTS: IFN-γat 0.1 to 5μg/L efficiently down regulated HBsAg expression in transduced HepG2 cells. At 5μg/L, IFN-γalso suppressed HBV DNA replication in these cells. While treatment with a combination of lamivudine and IFN-γshowed no additive effect, sequential treatment first with lamivudine and then IFN-γwas found to be promising. In this culture system the best HBV suppression was observed with a pulse of 2μmol/L lamivudine for two days, followed by 1μg/L IFN-γfor another four days. Compared to treatment with lamivudine alone, the sequential use of 0.2μmol/L lamivudine for two days, followed by 5μg/L IFN-γfor six days showed a 72% reduction in HBV cccDNA pool. CONCLUSION: This in vitro study warrants further evaluation of a combination of IFN-γand lamivudine, especially in IFN-αnon-responder chronic hepatitis B patients. A reduced duration of lamivudine treatment would also restrict the emergence of drug-resistant HBV mutants.     

An Unusual Form of Skin Tuberculosis Following B.C.G. Vaccination

A 25-year-old female has had brown to erythematous telangiectatic patches and grouped papules on her face, neck, arm, and trunk since childhood following B.C.G. vaccination. Histopathologically, the lesions consisted of hyperkeratosis, slight acanthosis, tuberculoid granulomas with some Langerhans type giant cells in the mid-dermis. Although various forms of cutaneous tuberculosis after B.C.G. vaccination have been reported, it was difficult for us to assign the patient's skin lesion to any specific disease entity. Remission of her cutaneous lesions occurred clinically and histopathologically after treatment with isoniazid and rifampin.     

甲乙型肝炎血清MAO同工酶活性变化研究

用荧光分光光度法检测了血清单胺氧化酶（ＭＡＯ）同工酶Ａ（ＭＡＯ－Ａ）和同工酶Ｂ（ＭＡＯ－Ｂ）活性，结果表明血清ＭＡＯ－Ｂ活性急性期甲肝组较正常对照组显著升高，慢性期乙肝极显著升高；二型肝炎组的ＭＡＯ－Ａ活性升高程度无统计学意义。二型肝炎ＭＡＯ同工酶活性改变与其它肝功生化指标无明显相关性，表现血清ＭＡＯ同工酶活性与肝功损害程度不相关。     

糖尿病中促动脉粥样硬化因素的探讨

我们对64例糖尿病患者和20名正常人的糖代谢、脂代谢、血小板和血管内皮细胞前列腺素代谢的水平进行了临床观察。发现糖尿病患者载脂蛋白B、低密度脂蛋白胆固醇、总脂固醇、甘油三酯和血栓素B_2的浓度均有不同程度的升高,而载脂蛋白A_1、高密度脂蛋白胆固醇和6-酮前列腺素F_(1α)的浓度则下降。同时糖代谢异常与脂代谢紊乱、糖代谢异常与前列腺素代谢物水平、以及脂代谢紊乱与前列腺素代谢物水平之间均无明显关系。推想糖尿病中促动脉粥样硬化的各种高危因素可能从不同的角度作用于血管壁,促进动脉粥样硬化的发生和发展。     

Human tonsil,blood and bone marrow in vivo-induced B cells capable of spontaneous and high-rate immunoglobulin secretion in vitro: Differences in the requirements for factors and for adherent and bone marrow stromal cells,as well as distinctive adhesion molecule expression

Human B cells capable of spontaneous IgG secretion are commonly found in circulation and in lymphoid tissues such as tonsil and bone marrow (BM). The present study compares the mechanisms that regulate tonsil, blood and BM B cells capable of spontaneous IgG secretion. The BM cell subset produced IgG during a markedly longer period of time (14 days) than did tonsil and blood cell subsets (2–3 days). Blood and BM, but not tonsil, B cell IgG secretion depended on the presence of adherent cells, as demonstrated by adherent cell depletion and re-addition experiments. Stromal BM cells supported linear IgG secretion by non-adherent BM cells for 2 weeks, but were unable to prolong the short-term IgG secretion by tonsil and blood cells. Different factors induced IgG secretion in each of the three B cell populations as optimal IgG secretion by tonsil, blood or BM cell subsets required either tumor necrosis factor-α, interleukin-6 or fibronectin + interleukin-6, respectively. Finally, these populations also showed differences in the expression of adhesion molecules; the tonsilar cell subset was PNA^+/? CD44⁺ CD49d⁺ CD49e^? Leu-8^+/?, the blood cell subset was PNA^? CD44^+/? CD49d⁺ CD49e^? Leu-8⁺ and the BM cell subset was PNA^? CD44^+/? CD49d⁺ CD49e^? Leu-8^?. These results suggest that the mechanisms controlling the final differentiation and the expression of adhesion molecules in these B lymphocytes exhibit territorial specificity.     

Abnormalities in immune regulation precede the development of multiple myeloma.

Immunosuppression of immunoglobulin synthesis seen in patients with multiple myeloma is in part due to immunosuppressive CD5 positive B cells. In a 13 year longitudinal study of an IgA-deficient blood donor who developed multiple myeloma, the presence of immunosuppressive CD5 positive B cells and T cells preceded the diagnosis of overt multiple myeloma and the appearance of immunosuppressive monocytes. These data argue that certain immune defects may be involved in the development of myeloma and are not simply a consequence of overt malignancy.     

前列腺素E1治疗慢性乙型肝炎黄疸的观察

目的观察前列腺素E1治疗慢性乙型肝炎重度黄疸的疗效。方法在综合治疗基础上，分别使用前列腺素E1（治疗组）和门冬氨酸钾镁（对照组）治疗慢性乙型肝炎重度黄疸患者各35例，并观察其症状、体征及肝、肾功能等，疗程4周。结果治疗组的症状、体征及肝功能指标及总有效率，均显著优于对照组，两组比较差异有显著意义（P〈0．05）。结论前列腺素E1治疗慢性乙型肝炎重度黄疸能显著地促进黄疸消退和改善肝功能。     

青天葵抗甲、乙型流感病毒作用研究

目的研究青天葵在体外抗甲、乙型流感病毒株作用。方法选用狗肾细胞培养法考察青天葵不同极性部位对甲型(FM1)、乙型(昆40B)流感病毒的作用。结果青天葵水溶性部位对甲型流感病毒FM1有抑制作用。结论青天葵具有体外抗甲型流感病毒作用。     

乙型肝炎与肝硬化和肝细胞癌的关系

近年来,应用免疫组织化学技术观察肝组织内乙型肝炎表面抗原(HBsAg)的研究屡有报导。大多数作者认为乙型肝炎在肝硬化、肝癌的发病中起重要作用;但有的流行病学研究则认为在某些地区,肝炎不是肝癌的病因。我省是肝癌高发区之一,关于这方面尚未见有报道。本文应用免疫酶法标记定位观察肝硬化、肝癌病人肝组织中HBsAg,以探讨本地区肝炎与肝硬化和肝细胞癌的关系。     

Reduced 293T cell susceptibility to acrolein due to aldose reductase-like-1 protein expression.

Acrolein is a highly reactive alpha,beta-unsaturated aldehyde produced endogenously during lipid peroxidation and naturally distributed pervasively in living environments, posing serious threats to human health if not properly metabolized. In this study, we report aldose reductase-like-1 (ARL-1) as a novel enzyme that catalyzes the reduction of acrolein and protects cells from their toxicity. Using purified ARL-1 protein, we determined its enzymatic activity in response to acrolein and defined its steady-state kinetics with K(m) and V(max) at 0.110 +/- 0.012 mM and 3122.0 +/- 64.7 nmol/mg protein/min, respectively. By introducing a functional Enhanced Green Fluorescent Protein (EGFP)/ARL-1 fusion protein into 293T cells, we demonstrated that plating efficiency in liquid culture and focus formation in soft agar increased by more than 60% (p < 0.05), compared to the vector control cells. More significantly, at a low dose of 5 microM acrolein, EGFP/ARL-1 expression enhanced both plating efficiency and focus formation by more than threefold, and the foci (in soft agar) of 293T cells expressing EGFP/ARL-1 were significantly larger than those of the vector control cells. At high concentrations of acrolein (25 and 50 microM), EGFP/ARL-1 protein prevented oncotic death of 293T cells induced by acrolein. In summary, our data demonstrated for the first time that the ARL-1 protein protects 293T cells from acrolein toxicity. Due to the high toxicity and wide distribution of acrolein, this finding is important to the understanding of its detoxification mechanisms.