Atheromatous plaque macrophages produce plasminogen activator inhibitor type-1 and stimulate its production by endothelial cells and vascular smooth muscle cells

The capacity of macrophages to influence directly and indirectly fibrinolytic processes in atherosclerosis was studied using macrophages isolated from atherosclerotic plaques of patients undergoing surgical repair of distal aortic and femoral arteries. These cells were characterized by their morphology, adherence, esterase positivity, and expression of CD14 antigen. Production of plasminogen activator inhibitor type-1 (PAI-1) by plaque macrophages (6.7 +/- 2.7 ng/10(5) cells/24 hours [mean +/- SEM]) was significantly greater than PAI-1 production by blood monocytes isolated simultaneously from the same patients (1.8 +/- 1.5 ng/10(5) cells/24 hours). Production of tissue type plasminogen activator and urokinase type was not augmented compared to blood monocytes. Conditioned medium from cultured plaque macrophages significantly increased production of PAI-1 by endothelial cells (85 +/- 11% above basal) and vascular smooth muscle cells (25 +/- 10%) in vitro. This response was significantly greater than the response to monocyte-conditioned medium (endothelial cells 38 +/- 11%, vascular smooth muscle cells 2.5 +/- 2.0%). Stimulation of endothelial cell PAI-1 production by macrophage-conditioned medium was partially inhibitable by a monoclonal antibody to transforming growth factor-beta. Tissue type plasminogen activator production by endothelial cells and vascular smooth muscle cells was not affected by plaque macrophage- or monocyte-conditioned medium. Urokinase type plasminogen activator production by endothelial cells and vascular smooth muscle cells was undetectable in control medium and was augmented to similar levels in response to plaque macrophage- and monocyte-conditioned media. These results demonstrate upregulation of PAI-1 production by macrophages in atheromatous plaques and the capacity of soluble products from plaque macrophages to upregulate PAI-1 production by endothelial cells and vascular smooth muscle cells in vitro. These data suggest that macrophages in atherosclerotic plaques may inhibit thrombolysis both directly and indirectly by effects of their soluble products on endothelial cells and vascular smooth muscle cells.     

Distribution of alpha 1A, alpha 1B and alpha 1E voltage-dependent calcium channel subunits in the human hippocampus and parahippocampal gyrus

The distribution of voltage-dependent calcium channel subunits in the central nervous system may provide information about the function of these channels. The present study examined the distribution of three alpha-1 subunits, alpha 1A, alpha 1B and alpha 1E, in the normal human hippocampal formation and parahippocampal gyrus using the techniques of in situ hybridization and immunocytochemistry. All three subunit mRNAs appeared to be similarly localized, with high levels of expression in the dentate granule and CA pyramidal layer. At the protein level, alpha 1A, alpha 1B and alpha 1E subunits were differentially localized. In general, alpha 1A-immunoreactivity was most intense in cell bodies and dendritic processes, including dentate granule cells, CA3 pyramidal cells and entorhinal cortex pre-alpha and pri-alpha cells. The alpha 1B antibody exhibited relatively weak staining of cell bodies but stronger staining of neuropil, especially in certain regions of high synaptic density such as the polymorphic layer of the dentate gyrus and the stratum lucidum and radiatum of the CA regions. The alpha 1E staining pattern shared features in common with both alpha 1A and alpha 1B, with strong immunoreactivity in dentate granule, CA3 pyramidal and entorhinal cortex pri-alpha cells, as well as staining of the CA3 stratum lucidum. These findings suggest regions in which particular subunits may be involved in synaptic communication. For example, comparison of alpha 1B and alpha 1E staining in the CA3 stratum lucidum with calbindin-immuno-reactivity suggested that these two calcium channels subunits may be localized presynaptically in mossy fibre terminals and therefore may be involved in neurotransmitter release from these terminals.     

Integrated modelling under uncertainty in watershed-level assessment and management.

Uncertainty in water quality model predictions is inevitably high due to natural stochasticity, model uncertainty, and parameter uncertainty. An integrated modelling system (modified-BASINS) under uncertainty is described and demonstrated for use in receiving-water quality prediction and watershed management. A Monte Carlo simulation was used to investigate the effect of various uncertainty types on output prediction. Without pollution control measures in the watershed, the concentrations of total nitrogen (T-N) and total phosphorus (T-P) in the Hwaong Reservoir, considering three uncertainty types, would be less than about 4.4 and 0.23 mg L(-1), respectively, in 2012, with 90% confidence. The effects of two watershed management practices, wastewater treatment plants (WWTP) and constructed wetlands (WETLAND), were evaluated. The combined scenario (WWTP + WETLAND) was the most effective at improving reservoir water quality, bringing concentrations of T-N and T-P in the Hwaong Reservoir to less than 3.4 and 0.14 mg L(-1), 24 and 41% improvements, respectively, with 90% confidence. Overall, the Monte Carlo simulation in the integrated modelling system was practical for estimating uncertainty and reliable in water quality prediction. The approach described here may allow decisions to be made based on the probability and level of risk, and its application is recommended.     

Substitution of the human beta-spectrin promoter for the human agamma-globin promoter prevents silencing of a linked human beta-globin gene in transgenic mice

During development, changes occur in both the sites of erythropoiesis and the globin genes expressed at each developmental stage. Previous work has shown that high-level expression of human beta-like globin genes in transgenic mice requires the presence of the locus control region (LCR). Models of hemoglobin switching propose that the LCR and/or stage-specific elements interact with globin gene sequences to activate specific genes in erythroid cells. To test these models, we generated transgenic mice which contain the human Agamma-globin gene linked to a 576-bp fragment containing the human beta-spectrin promoter. In these mice, the beta-spectrin Agamma-globin (betasp/Agamma) transgene was expressed at high levels in erythroid cells throughout development. Transgenic mice containing a 40-kb cosmid construct with the micro-LCR, betasp/Agamma-, psibeta-, delta-, and beta-globin genes showed no developmental switching and expressed both human gamma- and beta-globin mRNAs in erythroid cells throughout development. Mice containing control cosmids with the Agamma-globin gene promoter showed developmental switching and expressed Agamma-globin mRNA in yolk sac and fetal liver erythroid cells and beta-globin mRNA in fetal liver and adult erythroid cells. Our results suggest that replacement of the gamma-globin promoter with the beta-spectrin promoter allows the expression of the beta-globin gene. We conclude that the gamma-globin promoter is necessary and sufficient to suppress the expression of the beta-globin gene in yolk sac erythroid cells.     

一种微机控制的多测头凸轮轴测量系统

本文介绍一种由机械装置，高精度圆光栅编码器，光栅位移传感器，微型计算机，接口控制电路等组成的多测头凸轮轴测量系统，该系统安装调整方便，定位准确，测量精度高，操作简单，工作可靠，能快速实现对凸轮轴的自动测量。     

Increasing breast and cervical cancer screening in low-income women

Active cytomegalovirus (CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS) was treated with an intraocular sustained-release ganciclovir implant. A total number of 19 implants were performed in 15 eyes of 9 AIDS patients. The intraocular sustained-release ganciclovir was effective in preventing reactivation of CMV retinitis in 15 of the 19 implants, ineffective in 3, and undetermined in 1. All ineffective cases had been resistant to ganciclovir therapy before the implants. Vision after the therapy was maintained at better than 0.5 except for one eye. There were no serious ocular complications caused by the therapy. Among 5 patients with unilateral CMV retinitis, 2 unaffected eyes developed CMV retinitis during this therapy. In addition, another patient developed presumed CMV infection in other systemic organs. Based on these data, the intraocular sustained-release ganciclovir implant was considered to be useful for the treatment of CMV retinitis in AIDS.     

Ergonomics in rehabilitation: a comparison of two methods of moving an empty manual wheelchair short distances

Phthalimidomethyl derivatives 1, encompassing a wide range of leaving group abilities, are rapidly hydrolysed to the corresponding phthalamic acid via rate-determining attack at the phthalimide carbonyl group.