Granulocyte colony-stimulating factor receptors in human acute myelocytic leukemia

The binding of granulocyte colony-stimulating factor (G-CSF) to normal and human acute myeloid leukemia (AML) cells was investigated with radiolabeled recombinant human G-CSF (rhG-CSF). In all 14 cases of primary AML specific receptors for G-CSF were demonstrated on purified blast cells. The average numbers of G-CSF receptors ranged from very low to 428 receptors per cell (mean). Normal granulocytes showed G-CSF binding sites on their surface at higher densities (703 to 1,296 sites per cell). G-CSF receptors appeared to be of a single affinity type with a dissociation constant (kd) ranging between 214 and 378 pmol/L for AML blasts and 405 to 648 pmol/L for granulocytes. In 12 of 14 cases, including those with relatively low specific binding, G-CSF was a potent inducer of DNA synthesis of blasts in vitro; therefore, apparently relatively few receptors are required to permit activation of AML cell growth. However, in two cases cell cycling was not activated in response to G-CSF despite G-CSF receptor availability. The results show that G-CSF receptors of high affinity are frequently expressed on the blasts of human AML, but their presence may not be a strict indicator of the proliferative responsiveness of the cells to G- CSF.     

Critical role of CD28/B7 costimulation in the development of human Th2 cytokine-producing cells

CD28 is a major costimulatory signal receptor for T cells. We have used human naive CD4+ cells from cord blood to analyze the effect of the CD28/B7 costimulatory pathway on development of T helper (Th) subsets. We show that CD28 costimulation is critical for development of the Th2 cytokine-producing cells and that in the absence of CD28 costimulation, cells are not primed to produce Th2 cytokines and consequently "default" to the Th1 subset, independent of the presence of exogenous cytokines. After CD28 costimulation, cells differentiate into a subset that produces Th2 cytokines. However, further CD28 costimulation is not required to maintain Th2 cytokine production. We conclude that D28 costimulation is critical for the development of Th0 and Th2 subsets, but not for the maintenance of cytokine production.     

维A类化合物4-APR抑制肿瘤侵袭、转移的作用

用体内外实验模型,研究了新维A类化合物4-乙酰胺苯基维A酸酯(4-APR)对肿瘤侵袭、转移的抑制作用。4-APR 43.3mg·kg^-1po即能减少小鼠Lewis肺癌的自发性肺转移瘤数。半体内实验证明4-APR10^-5mol·L^-1和10^-6mol·L^-1对B16-F10癌细胞的人工肺转移瘤数分别抑制67.9%和36.6%。体外实验显示,4-APR对B16-F10细胞侵袭重组基底膜的抑制率分别为54.2%和41.9%。     

Temporal Contribution of Myeloid-Lineage TLR4 to the Transition to Chronic Pain: A Focus on Sex Differences

Complex regional pain syndrome (CRPS) is a chronic pain disorder with a clear acute-to-chronic transition. Preclinical studies demonstrate that toll-like receptor 4 (TLR4), expressed by myeloid-lineage cells, astrocytes, and neurons, mediates a sex-dependent transition to chronic pain; however, evidence is lacking on which exact TLR4-expressing cells are responsible. We used complementary pharmacologic and transgenic approaches in mice to more specifically manipulate myeloid-lineage TLR4 and outline its contribution to the transition from acute-to-chronic CRPS based on three key variables: location (peripheral vs central), timing (prevention vs treatment), and sex (male vs female). We demonstrate that systemic TLR4 antagonism is more effective at improving chronic allodynia trajectory when administered at the time of injury (early) in the tibial fracture model of CRPS in both sexes. In order to clarify the contribution of myeloid-lineage cells peripherally (macrophages) or centrally (microglia), we rigorously characterize a novel spatiotemporal transgenic mouse line, Cx3CR1-Cre^ERT2-eYFP;TLR4^fl/fl (TLR4 cKO) to specifically knock out TLR4 only in microglia and no other myeloid-lineage cells. Using this transgenic mouse, we find that early TLR4 cKO results in profound improvement in chronic, but not acute, allodynia in males, with a significant but less robust effect in females. In contrast, late TLR4 cKO results in partial improvement in allodynia in both sexes, suggesting that downstream cellular or molecular TLR4-independent events may have already been triggered. Overall, we find that the contribution of TLR4 is time- and microglia-dependent in both sexes; however, females also rely on peripheral myeloid-lineage (or other TLR4 expressing) cells to trigger chronic pain.SIGNIFICANCE STATEMENT The contribution of myeloid cell TLR4 to sex-specific pain progression remains controversial. We used complementary pharmacologic and transgenic approaches to specifically manipulate TLR4 based on three key variables: location (peripheral vs central), timing (prevention vs treatment), and sex (male vs female). We discovered that microglial TLR4 contributes to early pain progression in males, and to a lesser extent in females. We further found that maintenance of chronic pain likely occurs through myeloid TLR4-independent mechanisms in both sexes. Together, we define a more nuanced contribution of this receptor to the acute-to-chronic pain transition in a mouse model of complex regional pain syndrome.     

炎宁冲剂的抗炎与解热作用研究

目的：研究炎宁冲剂的抗炎与解热作用。方法：采用角叉菜胶致大鼠足跖炎性肿胀。二甲苯致小鼠耳毛细血管通透性增高,以及大鼠皮下羧甲基纤维素囊中白细胞出游等急性炎症模型研究炎宁冲剂的抗炎作用。采用啤酒酵母液引起家兔发热的方法研究炎宁冲剂的解热作用。结果：炎宁冲剂对以上实验动物均具有明显的抗炎和解热作用。结论：炎宁冲剂对急性炎症具有明显的抗炎作用。对啤酒酵母液引起家兔发热具有明显解热作用。