环孢菌素A阻断人HL-60抗药性细胞于G1期而诱导敏感细胞凋亡

进一步研究了抗三尖杉酯碱的HL-60细胞(HR20)抗细胞凋亡的机制及该抗性和抗药性的关系。结果表明,环孢菌素A(CsA)20,10μg·ml^-1诱导HL-60细胞发生凋亡,而阻断HR20细胞于G₁期,就不能诱导细胞发生凋亡。低浓度的CsA明显增加柔红霉素在HR20细胞内的积聚,其逆转抗药性作用与阻断细胞周期运行无关。CsA10μg·ml^-1处理HR20细胞,可引起50kDa的蛋白质高度磷酸化。结果提示:环孢菌素A阻断抗三尖杉酯碱的HL-60细胞于G₁期,而诱导敏感的HL-60细胞发生凋亡,其阻断作用与抗药性无关。     

Prevalence of, and risk factors for, hepatitis C virus infection among recent initiates to injecting in London and Glasgow: cross sectional analysis

Our aim was to compare the prevalence of antibody to hepatitis C virus (anti-HCV) among recently initiated injecting drug users (IDUs) in London and Glasgow, and to identify risk factors which could explain differences in prevalence between the cities. Complementary studies of community recruited IDUs who had initiated injection drug use since 1996 were conducted during 2001-2002. Data on HCV risk behaviours were gathered using structured questionnaires with identical core questions and respondents were asked to provide an oral fluid specimen which was tested anonymously for anti-HCV but was linked to the questionnaire. Sensitivities of the anti-HCV assays for oral fluid were 92-96%. Prevalence of anti-HCV was 35% (122/354) in London and 57% (207/366) in Glasgow (P < 0.001). Multifactorially, factors significantly associated with raised odds of anti-HCV positivity were increasing length of injecting career, daily injection, polydrug use, having had a needlestick injury, and having served a prison sentence. In addition lower odds of anti-HCV positivity were associated with non-injection use of crack cocaine and recruitment from drug agencies. After adjustment for these factors, the increased odds of anti-HCV associated with being a Glasgow IDU were diminished but remained significant. HCV continues to be transmitted among the IDU population of both cities at high rates despite the availability of syringe exchange and methadone maintenance. Effectiveness of harm reduction interventions may be compromised by inadequate coverage and failure to reduce sufficiently the frequency of sharing different types of injecting equipment, as well as the high background prevalence of HCV, and its high infectivity. Comprehensive action is urgently required to reduce the incidence of HCV among injectors.     

An endogenous glycosylphosphatidylinositol-specific phospholipase D releases basic fibroblast growth factor-heparan sulfate proteoglycan complexes from human bone marrow cultures

Basic fibroblast growth factor (bFGF) is a hematopoietic cytokine that stimulates stromal and stem cell growth. It binds to a glycosylphosphatidylinositol (GPI)-anchored heparan sulfate proteoglycan on human bone marrow (BM) stromal cells. The bFGF- proteoglycan complex is biologically active and is released by addition of exogenous phosphatidylinositol-specific phospholipase C. In this study, we show the presence of an endogenous GPI-specific phospholipase D (GPI-PLD) that releases the bFGF-binding heparan sulfate proteoglycan and the variant surface glycoprotein (a model GPI-anchored protein) from BM cultures. An involvement of proteases in this process is unlikely, because released proteoglycan contained the GPI anchor component, ethanol-amine, and protease inhibitors did not diminish the release. The mechanism of release is likely to involve a GPI-PLD and not a GPI-specific phospholipase C, because the release of variant surface glycoprotein did not reveal an epitope called the cross- reacting determinant that is exposed by phospholipase C-catalyzed GPI anchor cleavage. In addition, phosphatidic acid (which is specifically a product of GPI-PLD-catalyzed anchor cleavage) was generated during the spontaneous release of the GPI-anchored variant surface glycoprotein. We also detected GPI-PLD-specific enzyme activity and mRNA in BM cells. Therefore, we conclude that an endogenous GPI-PLD releases bFGF-heparan sulfate proteoglycan complexes from human BM cultures. This mechanism of GPI anchor cleavage could be relevant for mobilizing biologically active bFGF in BM. An endogenous GPI-PLD could also release other GPI-anchored proteins important for hematopoiesis and other physiologic processes.     

26万女性队列人群中乳腺癌与人工流产关系的研究（上海）

目的：评估人工流产（指手术流产）对乳腺癌危险性的可能影响。方法：研究在上海267040例妇女的一项乳房自我检查随机试验的队列人群中进行，由队列研究和巢式病例对照研究两部分组成。结果：依据基线调查表采集的资料分析，人工流产不增加乳腺癌危险性。调整潜在的混淆因素后，OR=1．06（95％CI：0．91～1．25）。人工流产次数增加无危险性趋势增加。从更详细的652例乳腺癌病例和694例对照资料分析，得出相似的结果。人工流产发生在首次生育后不增加危险性；少数妇女在首次生育前人工流产以及妊娠13周后人工流产，虽然被观察到危险性有增加，但无显著性统计学意义。结论：在中国，人工流产不是乳腺癌发生的重要原因。     

Role of transferrin in the placental transfer of iron in the rabbit

The role of transferrin in the transfer of iron from mother to fetus was investigated in rabbits in the last third of gestation. The rabbits were injected intravenously with ¹³¹I-transferrin which had been saturated into ⁵⁹Fe chloride. The radioactivity of the different isotopes was estimated in both maternal and fetal blood samples. ⁵⁹Fe was shown to be capable of crossing the rabbit placenta at a different rate from that of transferrin. Increasing amounts of transferrin cross the rabbit placenta with advancing gestation. Maternal transferrin itself appears to play little part in the transfer of iron from mother to fetus in the rabbit.     

Hepatic drug metabolism and immunostimulation

When host defence mechanisms are stimulated there is a concomitant decrease in cytochrome P450 based drug biotransformation and elimination. This has resulted in a number of clinically important unwanted drug responses in patients with infections or inflammatory responses. The loss in cytochrome P450 is predominantly an effect at the level of the gene expression and the majority of enzyme forms examined to date are involved. Although the effect occurs predominantly in the liver it has been recently shown that inflammatory responses in the brain also cause a loss of the same enzyme forms in that organ. The loss of cytochrome P450 in the brain in response to localised inflammation is accompanied by a similar loss in the liver. The decrease of cytochrome P450 and its dependent drug biotransformation is of concern whenever drugs are used in patients with infections or disease states with an inflammatory component.     

The suppression of hepatic cytochrome P4504A mRNA mediated by the interferon inducer polyinosinic acid.polycytidylic acid.

Interferon and interferon inducers are well known to depress the cytochrome P450-dependent hepatic mixed-function oxidase system and cause a decrease in the capacity of the liver to metabolize drugs and xenobiotics. In this study we have shown that the interferon-mediated changes in an induced form of hepatic cytochrome P450 (CYP4A) are mediated via a depression in the levels of mRNA as assessed by Northern blot and slot blot analyses using a 20-base synthetic oligodeoxyribonucleotide hybridization probe. Rats were pretreated with clofibrate to maximize CYP4A mRNA levels prior to the administration of polyinosinic acid.polycytidylic acid (poly IC), an alpha/beta interferon inducer. Hepatic CYP4A mRNA levels were decreased by 49 and 30% at 6 and 24 hr, respectively, following poly IC administration. In hepatic microsomes cytochrome P450 and functional CYP4A as measured by lauric acid hydroxylation, were not affected at 6 hr, but were depressed by 39 and 27%, respectively, 24 hr following poly IC administration. These results suggest that interferon depresses induced levels of hepatic drug metabolism by lowering the level of cytochrome P450 mRNAs and subsequent synthesis of cytochrome P450 apoproteins.