Interleukin-4 induces a substance in bone marrow stromal cells that reversibly inhibits factor-dependent and factor-independent cell proliferation

Bone marrow-derived stromal cell monolayers pretreated with recombinant interleukin-4 (IL-4) inhibit the growth of hematopoietic cells. This was demonstrated by inhibition of fresh bone marrow-derived, IL-3- induced soft agar colonies as well as by inhibition of proliferation of IL-3-dependent cell lines and of a Friend virus-transformed erythroleukemic cell line. Pretreatment of stromal cells with IL-4 for five to seven days induced the inhibitory activity. IL-4 could then be removed before "plating" the bone marrow cells in soft agar, indicating that the inhibitory activity did not depend on the action of IL-4 on the precursors of the soft agar colonies. The inhibitory activity appears to be mediated by a soluble factor since inhibition was achieved even if the stromal cell layer was separated from the colony forming cells by an "empty" agar layer. However, supernatants of IL-4- induced stromal cell layers had no detectable inhibitory activity. The inhibitory action of the IL-4-pretreated stromal cell lines was not the result of killing of the precursor cells since it could be reversed if the agar layer containing the colony-forming cells was removed from the stromal cell layer and cultured with IL-3. Hydrocortisone (HC) blocked the inhibitory effect if added either in the IL-4 preincubation phase or during the colony formation stage, implying that HC blocked both induction of the inhibitory activity and its release or its effector function. A homogenous long-term stromal cell line could not be induced to exert the inhibitory activity; partial inhibition could be achieved with pure macrophages stimulated with IL-4 and CSF-1, suggesting that the inhibitory activity induced by IL-4 in mixed stromal cell layers may depend on a complex mechanism involving more than one cell type. Northern analysis of RNA from IL-4-induced and uninduced stromal cells indicated that IL-4 did not upregulate expression of CSF-1 or transforming growth factor-beta (TGF-beta) and only modestly increased expression of tumor necrosis factor, suggesting that these cytokines were not responsible for the inhibitory activity. The capacity of IL-4 to induce inhibitory activity in stromal cell layers suggests that IL-4 may play a role in the regulation of hematopoiesis.     

健康人心室复极的昼夜变化研究

目的 探讨健康人心室复极的昼夜变化规律. 方法 对34例健康体检者的24h动态心电图进行回顾性分析.测定其心率、Q-T间期、QRS波群起点至T波波峰的时间(Q-Tp间期).计算T波波峰至终点的时间(Tp-e时间)、心率校正的Q-T间期(Q-Tc间期)和Tp-e时间(Tp-ec时间)、Tp-e/Q-T值,并比较一天中8个等分时间段的上述参数. 结果 Q-T间期和Tp-e时间呈日间短、凌晨及午夜长的昼夜节律变化,各时间段差异有统计学意义(P<0.01或0.05);Q-T间期与心率呈高度负相关(r=-01796，P<0.01)．而Tp-e时间与心率呈低度负相关(r=-01267，P<0.01)；各时间段Q-Tc间期接近,而Tp-ec时间呈07:00～09:00最高、10:00～12:00次之、01:00～03:00最低的昼夜节律变化,各时间段差异有统计学意义(P<0.05),Tp-e／Q-T值昼夜变化节律与Tp-ec时间相近.结论 反映心室复极跨壁离散度的Tp-e时间除受心率影响外,尚受昼夜节律的影响.     

The Redox State of the Glutathione/Glutathione Disulfide Couple Mediates Intracellular Arginase Activation in HCT-116 Colon Cancer Cells

Background  

Emerging studies have implicated arginase hyperactivity in the dysregulation of nitric oxide synthesis, which can lead to the development of vascular disease and the promotion of tumor cell growth. Recently, we showed that cysteine, in the presence of molecular iron, promotes arginase activity by driving the Fenton reaction. However, the exact mechanism of arginase activation in the cell induced by oxidative stress is unknown.     

细胞因子在慢性肝衰竭合并全身炎症反应综合征病例中的意义

目的探讨TNF-α、IFN-γ、LPS、IL-10、IL-12、IL-18在慢性肝衰竭合并全身炎症反应综合征(SIRS)中的意义。方法运用双抗体夹心酶联免疫吸附法检测正常人、一般肝炎患者、慢性肝衰竭组的TNF-α、IFN-γ、LPS、IL-10、IL-12、IL-18。结果自正常对照组到一般肝炎组、慢性肝衰竭非SIRS组、慢性肝衰竭SIRS组,血清中TNF-α、LPS、IL-12及IL-18水平依次升高,IL-10分子水平依次减低,且各组间比较均具有显著性差异。结论TNF-α、LPS、IL-10、IL-12、IL-18水平可以反应出乙型肝炎患者的肝脏损伤程度和疾病严重程度,可能在慢性肝衰竭合并SIRS的发病过程中起到相当重要的作用。     

湖南省临床艾滋病检测筛查实验室基本情况调查

目的了解各级临床实验室开展HIV血清学筛查试验的情况。方法采用问卷调查方式对141家临床艾滋病检测筛查实验室进行调查,利用Excel表建立数据库并进行分析。结果141家实验室2006年度共检测样本303045份,筛查阳性样本2404份,确认阳性样本276份,筛查阳性检出率和确认符合率分别为0.09%和11.48%。送检样本最多的科室是外、内、急诊和妇儿科。多数实验室采用国产酶联免疫吸附试剂。多数实验室缺少生物安全防护设备。结论进一步加强对实验室的管理,提高检测质量。     

Peripheral lymph node helper T-cell recovery after syngeneic bone marrow transplantation in mice prepared with either gamma-irradiation or busulfan

The optimum marrow ablative regimen for preparing recipients of bone marrow transplantation (BMT) has not been established. gamma- Irradiation, but not busulfan, produces a characteristic microvascular injury pattern which results in depressed capacity of normal lymphocytes to localize into the lymph nodes of syngeneic murine BMT recipients. Since peripheral lymph nodes are important sites for initiation and amplification of immune responses, the preparative regimen might delay recovery of regionally compartmentalized immune functions after BMT. We evaluated the effects of busulfan and gamma- irradiation on the phenotypic and functional reconstitution of helper T- cell function within the peripheral lymph nodes of BMT recipients. Both marrow ablative regimens caused a protracted delay in regeneration of peripheral lymph node CD4+ T cells. Specific helper T-cell functions, such as contact hypersensitivity and alloantigen responses, remained significantly depressed in the lymph nodes of irradiated mice for prolonged periods (up to 60 weeks). These responses recovered more rapidly in busulfan-treated BMT recipients. In contrast, the capacity of peripheral lymph node T cells to provide "help" for antigen-specific immunoglobulin production was only transiently depressed by either preparative regimen. Our experiments confirm the hypothesis that the marrow ablative regimen, particularly gamma-irradiation, may contribute to the period of immunodeficiency which follows BMT. The pattern of immune recovery observed suggests that preparative total body irradiation (TBI) may selectively depress the regional recovery of the TH1 [interleukin-2 (IL-2) and gamma-interferon (gamma-IFN) secreting] lymphocyte subset.     

Patients who develop inflammatory polyarthritis (IP) after immunization are clinically indistinguishable from other patients with IP

Musculoskeletal symptoms may occur following various types of immunization, and it has also been suggested that, like infection, immunization may act as a trigger for rheumatoid arthritis (RA). A total of 48 of 898 (5.3%) patients with early inflammatory polyarthritis (IP) referred to the Norfolk Arthritis Register reported an immunization in the 6 weeks prior to symptom onset. There were no important clinical or demographic differences between the 48 immunized patients and 185 consecutive patients who did not report prior immunization. In addition, the frequencies of HLA-DRB1*01. *04 and the shared epitope in 33 of the immunized patients were similar to those in the 185 non-immunized patients and to those in 136 healthy controls. Further results from a case-control study suggest that the rate of immunization is higher amongst cases (5.5%) than age- and sex-matched controls (2.8%). In a small number of susceptible individuals, immunization may thus act as a trigger for RA.      

Recycling with nicotine patches in smoking cessation

The aim was to evaluate if recycling of failures from a smoking cessation study may be of value. The study comprised 126 smokers (50%) of 252 failures, from a double-blind smoking cessation trial with nicotine patch, who accepted recycling after 1 year. Subjects were allocated nicotine patches delivering 15, 20 or 25 mg of nicotine (over 16 hours) according to their base-line saliva cotinine concentrations in an open trial. The treatment period was 12 weeks followed by tapering over 6 weeks. The percentage of quitters after 3, 12, 26, and 52 weeks was 44, 20, 7 and 6%, respectively. After 26 weeks, all subjects had relapsed in the group previously treated with active nicotine patch compared with 12% abstainers in the previous placebo subjects. The sustained abstinence rate without slips after one year was 2%. Recycling does not seem to be of long-term clinical relevance in our set-up for subjects initially treated with nicotine, but of some value in subjects quitting without nicotine therapy initially.     

Compound heterozygosity for the shared epitope and the risk and severity of rheumatoid arthritis in extended pedigrees

The objective was to explore the role of HLA-DRB1 genes in determining disease severity in rheumatoid arthritis (RA). The population comprised extended pedigrees of 17 multicase RA families. Family members were genotyped for both HLA-DRB1 alleles using restriction fragment length polymorphism (RFLP). Identification of HLA-DRB1*04 variants was performed using the Multiplex ARMS-RFLP technique. Compound heterozygote individuals carrying two different alleles containing the shared epitope (SE) were at greatest risk of developing RA (odds ratio = 36, 95% CI 9.1-143). A synergistic or additive effect of these alleles is suggested. Individuals carrying no SE alleles expressed milder disease, as measured by the Spread Severity (SS) index, compared to compound heterozygotes (P = 0.045). Compound heterozygosity was not invariably associated with severe disease with six (50%) having clinically mild disease at a median age of 57.5 yr and median disease duration of 16 yr. Inheriting two different SE-bearing alleles results in an increased risk of RA and, on average, greater disease severity. This is not, however, invariably associated with severe disease, making it of limited use as a predictor of prognosis.