Myeloid differentiation mediated through retinoic acid receptor/retinoic X receptor (RXR) not RXR/RXR pathway

Retinoids, such as all-trans-retinoic acid and 9-cis-retinoic acid, are naturally occurring ligands of the nuclear retinoic acid receptors (RARs). In concert with binding of ligand, these receptors from heterodimers with the retinoic X receptor (RXR) and transactivate RAR/RXR-responsive genes. Retinoids can differentiate leukemic cell lines in vitro and induce clinically complete remissions in patients with acute promyelocytic leukemia. Synthetic ligands to the RAR and RXR receptors have been developed that selectively bind and activate RAR/RXR (TTAB) and RXR/RXR dimers (SR11217). We investigated the affect of these ligands, either alone or in combination, on in vitro growth and differentiation of cells from the HL-60, KG-1, THP-1, and WEHI-3 myeloid cell lines as well as on clonal growth of fresh myeloid leukemic blasts from patients. Clonal inhibition of proliferation of these cells was studied in soft agar cultures. Cells were plated in the presence of either one or a combination of retinoids at concentrations of 10(-5) to 10(-10) mol/L. TTAB inhibited 50% clonal growth at an effective dose (ED50) that was about 1,000-fold lower than the concentration of SR11217 required to achieve an ED50 for the same leukemic cells. Combination of both ligands at a variety of concentrations showed no synergistic effects. Superoxide production (nitroblue tetrazolium reduction) and CD11b expression as parameters of differentiation of HL-60 cells were also examined. Results paralleled those of clonal growth, with SR11217 being markedly less potent than TTAB. These results show that the ligand selective for RXR-homodimers has little effect on either inducing differentiation or inhibiting clonal growth of leukemic cells. The differentiating and antiproliferative effects of retinoids are mainly induced through RAR/RXR heterodimers, and development of therapeutic analogs should focus on this category of retinoids.     

毛茛甙的抗诱变作用及代谢转化

研究表明,毛茛甙可显著抑制MMC和MMS等诱变剂对沙门氏菌TA₁₀₀和TA102回复突变作用;对MMC诱发的小鼠PEC徽核抑制率达56.5%。代谢研究表明:毛茛甙抑制DNA生物合成的作用可被肝微粒体酶和胞浆液分别降低46和12%;RP-HPLC测定显示,体外毛茛甙可被肝微粒代谢转化。     

胆固醇的吸附氧化及差示脉冲伏安测定

胆固醇能在开路下吸附在悬汞电极的表面,并在电位扫描过程中发生氧化。在0.1 mol/LK₂HPO₄—KH₂PO₄缓冲溶液(pH 7.8)中,差示脉冲溶出峰电位在-0.08V,溶出电流与胆固醇浓度在10^-7～10^-6mol/L范围内呈线性关系。经5min富集,检测下限达8×10^-8mol/L。本文对胆固醇在电极上的吸附、氧化机理,测定条件和干扰情况进行了探讨,并提出了直接测定血清中游离胆固醇的方法。     

Volume and osmotic properties of human neutrophils

Quantitative models describing the dynamics of human neutrophils in the microcirculation require accurate morphometric parameters such as volume and surface membrane area. Using both a micropipette technique and video light microscopy (LM) to measure the diameters of the spherical cells, we have accurately determined the volume of the human neutrophil. Our value, 299 +/- 32 microns 3, is in good agreement with our earlier results, but 55% larger than that reported by Schmid- Schonbein et al (Blood 56:866, 1980). However, the measurements of Schmid-Schonbein et al were based on the actual mass of the cells derived from transmission electron microscopic (TEM) images. The membrane surface area, at lysis, was calculated to be 2.6 times its initial projected area. After lysis, the cells do not reduce their size, indicative of the possibility of a F-actin network formation that would stiffen the structure. Further, we show that neutrophils behave as ideal osmometers when exposed to anisotonic solutions at 21 degrees C, as predicted by the Boyle-Van't Hoff relationship. The calculated Ponder's value, R, is 0.77, which corresponds to 77% of the cell volume being osmotically active under isotonic conditions. However, at 37 degrees C, the cells are able to regulate their volumes toward the original volumes after an osmotic stress.     

10-羟基癸烯酸在动物体内吸收、分布、代谢和排泄

10-癸基癸烯酸(即10-HDA,定位标记为³H-10HDA),经小鼠和大鼠口服后,胃肠道吸收快,峰时均在1h,全身分布迅速广泛,与组织亲和力强,肝中放射性为最高,依次为肾、胰、脂肪、脑、脾、心和肺。平均Vd为9.71/kg。Ig和iv的T1/2β在12.6～22.7h。体内消除较缓慢,31 d内,尿粪中放射性累计排泄分别为给药量的85.4%和13.5%,提取尿和胆汁经分析结果主要以原形药物排出。血浆蛋白结合率为63%。血中放射—性时间曲线符合开放二室模型。