Role of accessory cells in cytokine production by T cells in chronic B- cell lymphocytic leukemia

We investigated the production of cytokines by highly purified T helper cells from B-cell chronic lymphocytic leukemia (B-CLL) patients stimulated by different activation pathways, and we studied the influence of various accessory cell populations on the pattern of the secretion of cytokines, including interleukin (IL)-2, IL-4, interferon- gamma (IFN-gamma), and IL-10. Neither a qualitative nor a quantitative difference in cytokine production and proliferative capacity was observed in CLL-derived purified T cells compared with normal individuals, when T cells were stimulated by different pathways, including CD3, CD2, and costimulation with CD28. Addition of autologous accessory cells (aAC), however, dramatically influenced the cytokine pattern of normal versus B-CLL-derived T cells. CLL cells as aAC caused a marked increase of IL-2, whereas IFN-gamma was only slightly induced and IL-4 was not influenced. In contrast, in normal individuals addition of aAC, which predominantly consisted of monocytes, resulted in a significant increase of IFN-gamma and a reduction of IL-4 secretion. IL-2 production was inhibited by higher concentrations of aAC. The increased stimulation of IL-2 production by CLL cells was not specific to the leukemic cell population, as purified B cells from normal individuals had the same effect. On the other hand, purified monocytes from CLL patients and controls both induced IFN-gamma production and inhibited IL-4 secretion. After antigen-specific stimulation with tetanus toxoid, cytokine secretion was influenced by the type of aAC in a similar pattern. We conclude that T helper cells derived from patients with B-CLL are intrinsically normal and that the predominance of B cells as accessory cells in CLL significantly alters the immune function of T helper cells in vitro.     

Phase I study of Topotecan, a new topoisomerase I inhibitor, in patients with refractory or relapsed acute leukemia

The purpose of this study was to define, in a phase I study in leukemia, the maximally tolerated dose (MTD), major toxicities, and possible antitumor activity of Topotecan, a new topoisomerase I (topo I) inhibitor. Topotecan was delivered by a 5-day continuous infusion every 3 to 4 weeks to patients with refractory or relapsed acute leukemia, at doses ranging from 3.5 mg/m2 to 18 mg/m2 per course. Twenty-seven patients were treated, including 17 patients with acute myelogenous or undifferentiated leukemia, 7 with acute lymphocytic leukemia, and 3 with chronic myelogenous leukemia in blastic phase. Severe mucositis was the dose-limiting toxicity occurring in two of five patients treated with Topotecan 11.8 mg/m2 per course; a third patient had prolonged myelosuppression. At the MTD of 10 mg/m2 per course, 1 of 12 patients had severe mucositis and 5 had mild-to- moderate mucositis. Nausea, vomiting, diarrhea, and prolonged myelosuppression were uncommon. Three patients (11%) achieved a complete response, two (7%) had a partial response, and one (4%) had a hematologic improvement. The overall complete plus partial response rate was 19%, and 24% in acute myelogenous or undifferentiated leukemia. A novel in vitro assay that quantifies Topotecan-stabilized topo I-DNA complexes in patient samples was used, which demonstrated heterogeneity in the ability of Topotecan to interact with topo I, the intracellular target of Topotecan. This phase I study defined the MTD of Topotecan to be 10 mg/m2 by continuous infusion over 5 days every 3 to 4 weeks in patients with refractory or relapsed acute leukemia. Severe mucositis was the dose-limiting toxicity. Future studies will define the precise activity of Topotecan in different leukemia subsets, its efficacy in combination with other antileukemic drugs, and correlations between Topotecan-induced topo I-DNA complex formation and individual patient response to Topotecan.     

Interferon-alpha stimulates production of interleukin-10 in activated CD4+ T cells and monocytes

In the present study, we investigated the effect of interferon-alpha (IFN-alpha) on the expression of interleukin-10 (IL-10) mRNA and protein synthesis in human monocytes and CD4+ T cells. In mononuclear cells, IFN-alpha induced expression of IL-10 mRNA and further enhanced lipopolysaccharide (LPS)-stimulated IL-10 expression. In purified monocytes, a strong expression of IL-10 mRNA induced by LPS was not further enhanced by IFN-alpha. In highly purified CD4+ T cells, IFN- alpha upregulated IL-10 mRNA upon activation with phytohemagglutinin and phorbol myristate acetate. In purified monocytes, an effect of IFN- alpha on IL-10 protein synthesis was dependent on costimulation with LPS. Maximal stimulation of IL-10 protein by IFN-alpha was seen after prolonged incubation periods of 48 to 96 hours, whereas IFN-gamma reduced IL-10 production in the early incubation period. Similar effects of IFN-alpha were observed in CD4+ T cells activated with CD3 and CD28 monoclonal antibodies. Addition of IFN-alpha caused an increase of IL-10 in culture supernatants of activated T-helper cells of more than 100% after 96 hours of incubation. In contrast, other cytokines, including IFN-gamma and IL-4, had no influence on IL-10 secretion stimulated by CD3 and CD28 in CD4+ T cells. In serum samples of IFN-alpha-treated individuals, we failed to detect an influence of cytokine treatment on IL-10 serum levels, confirming the requirement of additional activating signals for IFN-alpha-mediated effects on IL-10 synthesis. In conclusion, IFN-alpha enhances the late induction of IL- 10, which physiologically occurs upon stimulation of monocytes and T cells. Biologically, this effect might enhance the negative-feedback mechanism ascribed to IL-10, which limits inflammatory reactions.     

针式腹腔镜下胆囊切除术的临床应用

目的 与开腹胆囊切除术相比,腹腔镜胆囊切除术（ＬＣ）有减少术后不适和较少的创作,但仍有改进的余地。方法：为进一步减轻手术创伤,我们引进了针式腹间胆囊切除术,共２９例。结果 平均手术时间为７５分钟,１９例当天出院,１０例隔天出院,其中１例是胆总管探查。结论 针式航空 镜胆囊切除术是一种可靠的技术。     

玻片法单人份免疫分型试剂盒在白血病诊断中的应用

0引言白血病免疫分型是指用已知的单克隆抗体(单抗)鉴定细胞表面或胞质内的分化抗原的方法.该方法的临床应用有利于白血病的鉴别及诊断.我们采用单人份免疫分型试剂盒对128例白血病患者进行了免疫分型.     

Low vision aid in exudative macular degeneration treated by photodynamic therapy and thermal laser photocoagulation

To determine the efficacy of low vision rehabilitation (LVR) in patients with age-related macular degeneration (AMD) treated by photodynamic therapy (PDT) compared to those treated by thermal laser photocoagulation (TLP). · METHODS: A retrospective study was performed examining the files of 42 patients (42 eyes) with AMD who had been treated either by TLP (Group 1) and PDT (Group 2). Once AMD was considered to be inactive they underwent visual rehabilitation in the LVR Unit in order to increase their ability for distant and near vision. · RESULTS: Eighteen eyes had received PDT and 24 had received TLP. Average corrected visual acuity after laser therapy was 0.14 in Group 1, and 0.16 in Group 2. No statistically significant differences were found between both groups before and after laser therapy. Both groups showed improvement after LVR; however, statistically significant differences between both groups were found only for near vision. · CONCLUSION: Our findings suggest that even though both PDT and TLP are associated to a decreased visual acuity after treatment, LVR may be more successful for near vision among patients treated by PDT