Interleukin 4, interferon-gamma, and prostaglandin E impact the osteoclastic cell-forming potential of murine bone marrow macrophages

Interleukin 4 (IL-4) is an immune cytokine that inhibits bone resorption in mice and suppresses osteoclastic cell formation in vitro through an undefined mechanism. In this report, we have established the cellular identity of the IL-4 target cell using a variety of bone marrow/stromal cell coculture methods. Initially, we found that the majority of IL-4's inhibition of osteoclastic cell formation was due to its effect on bone marrow cells, not stromal cells. Consequently, bone marrow macrophages were used as osteoclastic cell progenitors after they had been transiently exposed to IL-4 (48 h), before the addition of stromal cells, 1,25-dihydroxyvitamin D3, and dexamethasone. In this circumstance, IL-4 impaired subsequent osteoclastic cell formation, suggesting that the macrophage may be potentially targeted by many factors known to influence osteoclast formation. Consequently, we discovered that interferon-gamma (IFN gamma), prostaglandin E (PGE), and cell-permeant cAMP analogs also impacted osteoclastic cell formation when used to selectively treat bone marrow macrophages. IFN gamma suppressed osteoclastic cell formation, whereas PGE and cAMP analog treatment led to the formation of significantly enlarged osteoclastic cells. Importantly, PGE antagonized the inhibitory effects of both IL-4 and IFN gamma on the osteoclastic cell-forming potential of bone marrow macrophages. Collectively, these findings establish bone marrow macrophages as osteoclastic cell precursors with the degree of their commitment to the osteoclast pathway sensitive to the effects of soluble mediators, including IL-4, IFN gamma, and PGE.     

Dynamic thermographic imaging for estimation of regional perfusion in the tuberculin reaction in healthy adults

A sensitive method for measurement of the volume of blood flow through the skin, based on the kinetics of reheating after localised cooling, is described in this paper. This method has been used to study the tuberculin reaction as a model of cutaneous delayed-type hypersensitivity (DHS) in man. Over the positive reaction there is accelerated reheating similar in kinetics and extent to that seen after maximal hyperaemia induced by intradermal injection of histamine or prostaglandin E2. The earlier phase of reheating (10-100 s) is more dependent on blood flow, whereas the later phase (100-300 s) is apparently more dependent on non-perfusion heat exchange mechanisms, including conduction. The reheat kinetic method is largely dependent on blood flow in the deep dermal vessels (diameter > 50 microns), whereas the alternative approach of measurement of the velocity of flow of erythrocytes in the microcirculation by laser Doppler (LD) flowmetry gives results biased towards the most superficial dermal circulation. Previous studies with LD flowmetry have shown that the blood velocity is greatest at the centre of weak and strong reactions, while in the most intense reactions it is raised at the centre but maximal at the periphery (central relative slowing, CRS) raising the possibility of central ischaemia. The reheat kinetics approach has now indicated that the deep dermal circulation is not impaired in CRS reactions. It is concluded that there must be partial obstruction of the parts of the microcirculation communicating between the deep and superficial dermal plexuses, presumably from the accumulation of exudate oedema in the most intense tuberculin reactions.     

ACAT inhibitors derived from hetero-Diels-Alder cycloadducts of thioaldehydes

Acyl-CoA:cholesterol acyltransferase (ACAT) is the enzyme largely responsible for intracellular cholesterol esterification. A systemic inhibitor of ACAT is believed to be able to slow or even reverse the atherosclerotic process. Towards that goal, a series of cyclic sulfides, derived from the hetero-Diels-Alder reaction of thioaldehydes with 1,3-dienes, and bearing carboxamide substituents, were prepared and evaluated for in vitro (in several tissues and species) and ex vivo ACAT inhibition. Minor changes in subsequent structure were found to have a significant effect in optimization of the biological activity of this series of compounds.     

Information processing deficits associated with developmental coordination disorder: a meta-analysis of research findings

A meta-analysis was conducted to identify information processing factors that characterise children with Developmental Coordination Disorder (DCD). A total of 50 studies yielded 374 effect sizes based on 983 DCD and 987 control children. A mild generalised performance deficit was indicated, since motor-impaired children were inferior on almost all measures of information processing. There were, however, several areas where their deficiencies were more pronounced. The greatest deficiency was in visual-spatial processing. This was evident regardless of whether or not the tasks involved a motor component. Most other deficiencies were in the small-to-moderate range and included kinaesthetic and cross-modal processing. The findings support the notion that perceptual problems, particularly in the visual modality, are associated with difficulties in motor coordination.     

Use of a subcutaneous glucose sensor to detect decreases in glucose concentration prior to observation in blood

The development of a hypoglycemic alarm system using a subcutaneous glucose sensor implies that a decrease in blood glucose is rapidly followed by a decrease in the signal generated by the sensor. In a first set of experiments the linearity and the kinetics of the response of sensors implanted in the subcutaneous tissue of normal rats were investigated during a progressive increase in plasma glucose concentration: the sensitivities determined between 5 and 10 mM and between 10 and 15 mM were not significantly different, and a 5-10 min delay in the sensor's response was observed. In a second set of experiments, performed in diabetic rats, the kinetics of the decrease in subcutaneous glucose concentration following insulin administration was monitored during a decrease in plasma glucose level, from 15 to 3 mmol/L. During the 20 first min following insulin administration, the sensor monitored glucose concentration in subcutaneous tissue with no lag time. Subsequently, the decrease in the estimation of subcutaneous glucose concentration preceded that of plasma glucose. This phenomenon was not observed when the same sensors were investigated in vitro during a similar decrease in glucose concentration and may be due to a mechanism occurring in vivo, such as the effect of insulin on glucose transfer from the interstitial space to the cells surrounding the sensor. It reinforces the interest of the use of implantable glucose sensors as a part of a hypoglycemic alarm.     

Sidestream tobacco smoke exposure acutely alters human nasal mucociliary clearance

Nasal mucociliary clearance (NMC) is a biomarker of nasal mucosal function. Tobacco smokers have been shown to have abnormal NMC, but the acute effect of environmental tobacco smoke (ETS) on nonsmokers is unknown. This study evaluated acute tobacco smoke-induced alterations in NMC in 12 healthy adults. Subjects were studied on 2 days, separated by at least 1 week. Subjects underwent a 60-min controlled exposure at rest to air or sidestream tobacco smoke (SS) (15 ppm CO) in a controlled environmental chamber. One hour after the exposure, 99mTc-sulfur colloid was aerosolized throughout the nasal passage and counts were measured with a scintillation detector. Six out of 12 subjects showed more rapid clearance after smoke exposure than after air exposure, and 3/12 had rapid clearance on both days. However, substantial decreases in clearance occurred in 3/12 subjects, all of whom had a history of ETS rhinitis. In two subjects, more than 90% of the tracer remained 1 hr after tracer administration (2 hr after smoke exposure). Understanding the basis for biologic variability in the acute effect of tobacco smoke on NMC may advance our understanding of pathogenesis of chronic effects of ETS.     

Evaluating Ozone as a Remedial Treatment for Removing RDX from Unsaturated Soils

Years of wastewater discharge at the Department of Energy’s Pantex Plant have contaminated the vadose zone and underlying perched aquifer with hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX). Because the vadose zone is acting as a continual source of groundwater contamination, removing RDX from the unsaturated zone is paramount to prevent further contamination. We determined the efficacy of ozone to degrade and mineralize RDX. Solution experiments showed that ozone (27?mg?L?1; 150?mL?min?1) was effective in mineralizing 80% of the RDX (30?mg?RDX?L?1) provided that some Pantex soil was present to buffer the solution pH. Soil columns treated with ozone produced 50% RDX mineralization within 1 day and >80% within 7 day. Experiments designed to evaluate aerobic biodegradation following partial ozonation of a RDX solution showed that ozone-generated RDX products were much more biodegradable than untreated controls in aerobic microcosms (35 versus <0.3% cumulative mineralization). These results support the use of ozone as a remedial treatment for the contaminated vadose zone at the Pantex facility.     

混合信号SoC设计的现状与未来

从消费电子市场最容易得到的经验是集成为王。移动型战胜便携型,掌上型战胜移动型,而衬衫口袋型又超过掌上型。即使像游戏机这类桌面设备,时髦的外形和低制造成本目标也要靠更高集成度才能实现。这一趋势并不限于低成本的消费电子产品。军用、汽     

Remote sensing of species mixtures in conifer plantations using LiDAR height and intensity data

In even-aged, single species conifer plantations LiDAR height data can be modelled to provide accurate estimates of tree height and volume. However, it is apparent that growth models developed for single species stands are not directly transferable to a more general situation of mixed species plantations. This paper evaluates the ability of small footprint, dual-return, pulsed airborne LiDAR data to estimate the proportion of the productive species when mixed with a nurse crop in closed canopy plantations. A study area located in Galloway Forest District in Scotland is used as an example of Lodgepole pine and Sitka spruce mixed plantation; this area contains good examples of a wide range of pure and mixed species plantation types. Three species groups are studied: areas of pure Sitka spruce, areas of pure Lodgepole pine and areas where the two species have been planted together. Two approaches are assessed for detection of plantation mixtures: the first uses LiDAR intensity data to separate spruce and pine species and the second uses LiDAR-derived canopy density measures, coefficient of variation, skewness, percent of ground returns (which provides a measure of canopy openness) and the mean canopy height, which enables areas with height variations to be identified. From analysis of LiDAR data extracted from 54 study plots using logistic regression, the coefficient of variation and LiDAR intensity data provide the most useful predictors of the proportion of spruce in a pine/spruce mixture with coefficients of determination (R²) of 0.914 and 0.930 respectively. The method could be developed as a mapping tool, which in combination with existing inventory data should help to improve timber volume forecasting for mixed species even-aged plantations.