ABSTRACT
Doxorubicin is an anthracycline antitumor antibiotic with dose-dependent and cumulative cardiotoxicity. However, the necessity for serial cardiac evaluation is unknown in dogs without risk factors for dilated cardiomyopathy (DCM). This study aimed to investigate serial changes in echocardiographic and electrocardiographic measures in small- and medium-sized dogs after four doxorubicin doses. We included 17 dogs, weighting < 20â¯kg, with multicentric lymphoma. All dogs received doxorubicin over 30â¯min every 4 weeks as part of a multi-drug chemotherapy protocol. The average doxorubicin dose was 3.8 times per dog. Clinical cardiotoxicity was not observed during the monitoring period. The incidence of developing arrhythmia was not significantly associated with the number of doxorubicin doses received (P = 0.600). The development of valvular regurgitations and mitral regurgitation in these dogs was not significantly associated with the number of doxorubicin doses (P = 0.363 and P = 0.779, respectively). The other echocardiographic results were not significantly different between each evaluation. In conclusion, our results showed no significant cardiotoxicity under echocardiogram and electrocardiogram in small- and medium-sized dogs without risk factors for DCM after four doses of doxorubicin in a 30-minute infusion method.
Subject(s)
Antibiotics, Antineoplastic , Dog Diseases , Doxorubicin , Echocardiography , Electrocardiography , Lymphoma , Animals , Dogs , Doxorubicin/therapeutic use , Doxorubicin/administration & dosage , Dog Diseases/drug therapy , Antibiotics, Antineoplastic/therapeutic use , Antibiotics, Antineoplastic/administration & dosage , Antibiotics, Antineoplastic/adverse effects , Female , Male , Lymphoma/veterinary , Lymphoma/drug therapy , Echocardiography/veterinary , Electrocardiography/veterinary , Cardiotoxicity/veterinary , Cardiotoxicity/etiologyABSTRACT
We report the single-crystal growth of Mn2V2O7and the results of magnetic susceptibility, high-field magnetization up to 55 T and high-frequency electric spin resonance (ESR) measurements for its low-temperatureαphase. Two antiferromagnetic (AFM) ordering at 17.5 K and 3 K and obvious magnetic anisotropy are observed inα-Mn2V2O7upon cooling. In pulsed high magnetic fields, the compound reaches the saturation magnetic moment of â¼10.5µBfor each molecular formula at around 45 T after two undergoing AFM phase transitions atHc1≈ 16 T,Hc2≈ 34.5 T forH//[11-0] andHsf1= 2.5 T,Hsf2= 7 T forH//[001]. In these two directions, two and seven resonance modes are detected by ESR spectroscopy, respectively. Theω1andω2modes ofH//[11-0] can be well described by two-sublattice AFM resonance mode with two zero-field gaps at 94.51 GHz and 169.28 GHz, indicating a hard-axis feature. The seven modes forH//[001] are partially separated by the critical fields ofHsf1andHsf2, displaying the two signs of spin-flop transition. The fittings ofωc1andωc2modes yield zero-field gaps at 69.50 GHz and 84.73 GHz forH//[001], confirming the axis-type anisotropy. The saturated moment and gyromagnetic ratio indicate the Mn2+ion inα-Mn2V2O7is in a high spin state with orbital moment completely quenched. A quasi-one-dimensional magnetism with a zig-zag-chain spin configuration is suggested inα-Mn2V2O7, due to the special neighbor interactions caused by a distorted network structure with honeycomb layer.
ABSTRACT
With the wide use of immunosuppressive agents, life-threatening cytomegalovirus-associated acute respiratory failure occurs frequently. However, this condition is yet to be fully recognized and the therapeutic approach to it can only be based on comprehensive protocols rather than the biological characteristics of cytomegalovirus. We describe three acute respiratory failure events that were related to the pathogenicity of cytomegalovirus, the primary cytopathic effect and secondary antiviral immunity-mediated damage. All cytomegalovirus infection occurred after immunosuppressive usage while the acute respiratory failure events took place in different clinical settings. The first acute respiratory failure event originated from the immunoinflammatory response after cytomegalovirus infection was circumscribed, while the second resulted from cytomegalovirus reactivation and the third was caused by the combined effect of acute cytomegalovirus infection and the subsequent immunoinflammatory response. According to the clinical setting, corresponding therapeutic approaches (sequential or combined strategy) were carried out. All the patients here presented were responsive to the above therapeutic strategies. Consequently, cytomegalovirus-associated acute respiratory failure in systemic lupus erythematosus patients should be carefully differentiated and a sequential or combined strategy should be carried out according to the clinical setting. Overall, we find that there are three patterns of cytomegalovirus-associated acute respiratory failure in systemic lupus erythematosus patients and propose a novel therapeutic strategy in relation to cytomegalovirus biology.
Subject(s)
Cytomegalovirus Infections/complications , Immunosuppressive Agents/adverse effects , Lupus Erythematosus, Systemic/drug therapy , Respiratory Insufficiency/etiology , Acute Disease , Adolescent , Antiviral Agents/administration & dosage , Cytomegalovirus/isolation & purification , Cytomegalovirus Infections/etiology , Cytomegalovirus Infections/therapy , Female , Humans , Immunosuppressive Agents/administration & dosage , Male , Respiratory Insufficiency/therapy , Young AdultABSTRACT
Ammonia emissions vary greatly at a local scale, and effects (eutrophication, acidification) occur primarily close to sources. Therefore it is important that spatially distributed emission estimates are located as accurately as possible. The main source of ammonia emissions is agriculture, and therefore agricultural survey statistics are the most important input data to an ammonia emission inventory alongside per activity estimates of emission potential. In the UK, agricultural statistics are collected at farm level, but are aggregated to parish level, NUTS-3 level or regular grid resolution for distribution to users. In this study, the Modifiable Areal Unit Problem (MAUP), associated with such amalgamation, is investigated in the context of assessing the spatial distribution of ammonia sources for emission inventories. England was used as a test area to study the effects of the MAUP. Agricultural survey data at farm level (point data) were obtained under license and amalgamated to different areal units or zones: regular 1-km, 5-km, 10-km grids and parish level, before they were imported into the emission model. The results of using the survey data at different levels of amalgamation were assessed to estimate the effects of the MAUP on the spatial inventory. The analysis showed that the size and shape of aggregation zones applied to the farm-level agricultural statistics strongly affect the location of the emissions estimated by the model. If the zones are too small, this may result in false emission "hot spots", i.e., artificially high emission values that are in reality not confined to the zone to which they are allocated. Conversely, if the zones are too large, detail may be lost and emissions smoothed out, which may give a false impression of the spatial patterns and magnitude of emissions in those zones. The results of the study indicate that the MAUP has a significant effect on the location and local magnitude of emissions in spatial inventories where amalgamated, zonal data are used.
Subject(s)
Air Pollutants/analysis , Air Pollution/statistics & numerical data , Ammonia/analysis , Environmental Monitoring/methods , Agriculture , England , Models, Chemical , UncertaintyABSTRACT
Deposition of dissolved organic nitrogen (DON) in both bulk precipitation (BD) and canopy throughfall (TF) has been measured for the first time in the western Mediterranean. The study was carried out over a year from 2012 to 2013 at four evergreen holm oak forests located in the Iberian Peninsula: two sites in the Province of Barcelona (Northeastern Spain), one in the Province of Madrid (central Spain) and the fourth in the Province of Navarra (Northern Spain). In BD the annual volume weighted mean (VWM) concentration of DON ranged from 0.25 mg l(-1) in Madrid to 1.14 mg l(-1) in Navarra, whereas in TF it ranged from 0.93 mg l(-1) in Barcelona to 1.98 mg l(-1) in Madrid. The contribution of DON to total nitrogen deposition varied from 34% to 56% in BD in Barcelona and Navarra respectively, and from 38% in Barcelona to 72% in Madrid in TF. Agricultural activities and pollutants generated in metropolitan areas were identified as potential anthropogenic sources of DON at the study sites. Moreover, canopy uptake of DON in Navarra was found in spring and autumn, showing that organic nitrogen may be a supplementary nutrient for Mediterranean forests, assuming that a portion of the nitrogen taken up is assimilated during biologically active periods.
Subject(s)
Environmental Pollutants/analysis , Forests , Nitrogen/analysis , Quercus , Agriculture , Ecosystem , Environmental Monitoring , Environmental Pollutants/chemistry , Nitrogen/chemistry , Seasons , Spain , TreesABSTRACT
DNA vaccination is an attractive approach for eliciting antigen-specific immunity. In this study, we used magnetosomes (bacterial magnetic particles, BMPs) as carriers of a recombinant DNA composed of a secondary lymphoid tissue chemokine, human papillomavirus type E7 (HPV-E7) and Ig-Fc fragment (pSLC-E7-Fc) to generate a gene vaccine (BMP-V) for tumour immunotherapy. The results indicate that BMPs linked to DNA more efficiently in phosphate-buffered saline (pH=4-5) than in physiological saline. Efficient transfection of BMP-V in vitro and in vivo was achieved when a 600-mT static magnetic field was applied for 10 min. In a mouse tumour model, subcutaneous injection of BMP-V (5 µg, × 3 at 4-day intervals) plus magnetic exposure elicited systemic HPV-E7-specific immunity leading to significant tumour inhibition. The treated mice tolerated BMP-V immunisation well with no toxic side effects, as shown by histopathological examinations of major internal organs. Taken together, these results suggest that BMP can be used as a gene carrier to elicit a systemic immune response.
Subject(s)
Carcinoma, Lewis Lung/therapy , Gene Transfer Techniques , Magnetosomes , Melanoma, Experimental/therapy , Vaccines, DNA/administration & dosage , Animals , Carcinoma, Lewis Lung/immunology , Cell Line, Tumor , Female , Immunoglobulin Fragments , Melanoma, Experimental/immunology , Mice , Mice, Inbred C57BL , Papillomaviridae/genetics , Vaccines, DNA/immunologyABSTRACT
OX40 ligand (OX40L) and high-sensitivity C-reactive protein (hs-CRP) play important roles in the pathogenesis of atherosclerosis. In this study, consecutive patients with acute coronary syndrome (ACS; n = 90) or stable angina (SA; n = 40) and healthy control subjects (n = 50) were evaluated to assess plasma OX40L and serum hs-CRP levels in local coronary plaque and the femoral artery. OX40L and hs-CRP levels in the femoral artery were significantly higher in patients with ACS compared with controls. OX40L and hsCRP levels in local coronary plaque (OX40L(c) and hs-CRP(c), respectively) were significantly higher in ACS than in SA patients. OX40L and hs-CRP levels were positively correlated with each other and were also correlated with fibrinogen levels. The number of complex lesions was correlated with OX40L(c) and hs-CRP(c) levels. It is concluded that the OX40L(c) level was highly sensitive for evaluating the inflammatory response in ACS and elevated levels of OX40L(c) may be a valuable predictive marker for increased risk of atherosclerotic progression in ACS patients.
Subject(s)
Acute Coronary Syndrome/blood , Angina, Stable/blood , Biomarkers/blood , C-Reactive Protein/metabolism , Femoral Artery/metabolism , OX40 Ligand/blood , Plaque, Atherosclerotic/blood , Acute Coronary Syndrome/diagnosis , Angina, Stable/diagnosis , Case-Control Studies , Enzyme-Linked Immunosorbent Assay , Female , Femoral Artery/pathology , Follow-Up Studies , Humans , Male , Middle Aged , Plaque, Atherosclerotic/diagnosis , Prognosis , Sensitivity and SpecificityABSTRACT
The content of organic N has been shown in many studies to increase during the passage of rain water through forest canopies. The source of this organic N is unknown, but generally assumed to come from canopy processing of wet or dry-deposited inorganic N. There have been very few experimental studies in the field to address the canopy formation or loss of organic N. We report two studies: a Scots pine canopy exposed to ammonia gas, and a Sitka spruce canopy exposed to ammonium and nitrate as wet deposition. In both cases, organic N deposition in throughfall was increased, but only represented a small fraction (<10%) of the additional inorganic N supplied, suggesting a limited capacity for net organic N production, similar in both conifer canopies under Scottish summertime conditions, of less than 1.6 mmol N m(-2) mth(-1) (equivalent to 3 kg N ha(-1) y(-1)).
Subject(s)
Air Pollutants/analysis , Environmental Monitoring , Nitrogen/analysis , Trees/chemistry , Air Pollutants/chemistry , Air Pollutants/metabolism , Air Pollution/statistics & numerical data , Ammonia/chemistry , Nitrogen/chemistry , Nitrogen/metabolism , Picea/chemistry , Picea/metabolism , Pinus/chemistry , Pinus/metabolism , Rain/chemistry , Statistics as Topic , Trees/metabolismABSTRACT
A conditional time-averaged gradient (COTAG) system has been developed to provide direct long-term (weekly to monthly) average flux gradient measurements for a range of trace gases, between land and atmosphere. Over daily periods, atmospheric conditions can range from high stability, where the vertical gradients of ambient concentration are enhanced due to very small diffusivity, to highly unstable conditions, in which concentration gradients are small due to the intense turbulent activity of the surface layer. The large vertical gradients generated by high stability would bias the estimate of the actual flux: to avoid this, the COTAG system samples conditionally, within a carefully refined range of stability. A comparison with a continuous flux gradient system suggested that the removal of stable conditions from the sampling period does not substantially modify the evaluation of the long-term fluxes.
Subject(s)
Environmental Monitoring/economics , Environmental Monitoring/methods , Quaternary Ammonium Compounds/analysis , Sulfur Dioxide/analysis , Models, TheoreticalABSTRACT
The dry deposition of ammonia from the atmosphere to the surface can lead to eutrophication of sensitive ecosystems and acidification of the soil. A large proportion of the ammonia emitted from agricultural sources can be deposited within a few kilometres and, therefore, impacts of ammonia dry deposition often occur near to the source. To assess these impacts, short-range atmospheric dispersion models are often applied to simulate the emission, dispersion and deposition of ammonia. However, these models can be time-consuming to run and often require detailed input data and, therefore, for multiple assessments it is useful to have a method of screening to discard scenarios where impacts are expected to be negligible. The SCAIL model (Simple Calculation of Ammonia Impact Limits) has been developed for this purpose. SCAIL estimates the atmospheric concentration and dry deposition at the nearest edge of a sensitive ecosystem (receptor) downwind of an ammonia source. These estimates are calculated based on simple meteorological data, the emission rate of the source, land cover type and distance to the receptor. Analysis of the model predictions showed that uncertainty in the model input data leads to an uncertainty in concentration and dry deposition estimates of 25-30% and 40-45% respectively. Detailed atmospheric dispersion models will also have similar uncertainties since they use similar types of input data. Comparison of the concentration predictions with previous measurements made around eight farms showed that the model significantly underestimated concentrations although the model performance was similar to existing screening techniques. The measurement dataset was used to calibrate the SCAIL model which subsequently performed better, using independent verification data, than existing models calibrated in a similar way. The benefits of the SCAIL model are already being seen in the UK, where it is used to screen farms for potential impacts on statutory nature conservation areas.
Subject(s)
Air Pollutants/analysis , Ammonia/analysis , Models, TheoreticalABSTRACT
Ammonia emissions (NH3) are characterised by a high spatial variability at a local scale. When modelling the spatial distribution of NH3 emissions, it is important to provide robust emission estimates, since the model output is used to assess potential environmental impacts, e.g. exceedance of critical loads. The aim of this study was to provide a new, updated spatial NH3 emission inventory for the UK for the year 2000, based on an improved modelling approach and the use of updated input datasets. The AENEID model distributes NH3 emissions from a range of agricultural activities, such as grazing and housing of livestock, storage and spreading of manures, and fertilizer application, at a 1-km grid resolution over the most suitable landcover types. The results of the emission calculation for the year 2000 are analysed and the methodology is compared with a previous spatial emission inventory for 1996.
Subject(s)
Ammonia/analysis , Environmental Pollutants/analysis , Environmental Pollution/statistics & numerical data , Models, Theoretical , Agriculture , Air Pollutants/analysis , Animal Husbandry , Animals , Cattle , Environmental Monitoring/methods , Environmental Monitoring/statistics & numerical data , Female , Male , Manure , Poultry , Swine , United KingdomABSTRACT
We have recently identified a human homolog of a fungal nuclear migration protein (hNUDC) that binds specifically with the extracellular domain of thrombopoietin receptor (Mpl). Preliminary studies with human CD34(+) cells cultured in serum-free medium and normal mice showed that hNUDC appears to act as a cytokine, triggering many of the same responses as thrombopoietin (TPO). More intriguingly, recent data gained using a NIH 3T3 system have demonstrated that hNUDC exerts its biological activities through activation of Mpl. In this study, we further compared the biological functions of hNUDC with TPO in an EPO-dependent UT-7 cell line that was engineered to express the thrombopoietin receptor (Mpl). These Mpl-expressing cells following stimulation by either hNUDC or TPO exhibited overlapping patterns of megakaryocytic proliferation and differentiation, manifested by cell morphological change, polyploidy and expression of CD41(+). Similar with TPO, hNUDC induced a sustained activation of the extracellular signal-regulated protein kinases-1 and -2 (ERK1/2) as well as p38 mitogen-activated kinase (p38 MAPK) pathways and these activations were inhibited in the presence of PD98059 or SB203580. Further evidence is provided that PD98059 or SB203580 inhibited hNUDC- or TPO-induced cell proliferation and differentiation, suggesting that ERK1/2 and p38 MAPK pathways are necessary in megakaryocyte development.
Subject(s)
Cell Cycle Proteins/physiology , Cell Differentiation , Cell Proliferation , Megakaryocytes/cytology , Nuclear Proteins/physiology , Receptors, Thrombopoietin/metabolism , Cell Line, Tumor , Humans , Leukemia/pathology , Mitogen-Activated Protein Kinase 3/metabolism , Signal Transduction , Thrombopoietin/pharmacology , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
Recent research in nitrogen exchange with the atmosphere has separated research communities according to N form. The integrated perspective needed to quantify the net effect of N on greenhouse-gas balance is being addressed by the NitroEurope Integrated Project (NEU). Recent advances have depended on improved methodologies, while ongoing challenges include gas-aerosol interactions, organic nitrogen and N(2) fluxes. The NEU strategy applies a 3-tier Flux Network together with a Manipulation Network of global-change experiments, linked by common protocols to facilitate model application. Substantial progress has been made in modelling N fluxes, especially for N(2)O, NO and bi-directional NH(3) exchange. Landscape analysis represents an emerging challenge to address the spatial interactions between farms, fields, ecosystems, catchments and air dispersion/deposition. European up-scaling of N fluxes is highly uncertain and a key priority is for better data on agricultural practices. Finally, attention is needed to develop N flux verification procedures to assess compliance with international protocols.
Subject(s)
Air Pollutants/chemistry , Greenhouse Effect , Models, Chemical , Nitrogen Compounds/chemistry , Air Pollutants/analysis , Atmosphere , Ecosystem , Environmental Monitoring/methods , Europe , Nitrogen Compounds/analysisABSTRACT
The main source of atmospheric ammonia (NH3) in Scotland is livestock agriculture, which accounts for 85% of emissions. The local magnitude of emissions therefore depends on livestock density, type, and management, with major differences occurring in various parts of Scotland. Local differences in agricultural activities therefore result in a wide range of NH3 emissions, ranging from less than 0.2 kg N ha(-1) year(-1) in remote areas of the Scottish Highlands to over 100 kg N ha(-1) year-1 in areas with intensive poultry farming. Scotland can be divided loosely into upland and lowland areas, with NH3 emission being less than and more than 5 kg N ha(-1) year(-1), respectively. Many semi-natural ecosystems in Scotland are vulnerable to nitrogen deposition, including bogs, moorlands, and the woodland ground flora. Because NH3 emissions occur in the rural environment, the local deposition to sensitive ecosystems may be large, making it essential to assess the spatial distribution of NH3 emissions and deposition. A spatial model is applied here to map NH3 emissions and these estimates are applied in atmospheric dispersion and deposition models to estimate atmospheric concentrations of NH3 and NH4+, dry deposition of NH3, and wet deposition of NHx. Although there is a high level of local variability, modelled NH3 concentrations show good agreement with the National Ammonia Monitoring Network, while wet deposition is largest at high altitude sites in the south and west of Scotland. Comparison of the modelled NHx deposition fields with estimated thresholds for environmental effects ("critical loads") shows that thresholds are exceeded across most of lowland Scotland and the Southern Uplands. Only in the cleanest parts of the north and west is nitrogen deposition not a cause for concern. Given that the most intense effects occur within a few kilometres of sources, it is suggested that local spatial abatement policies would be a useful complement to traditional policies that mitigate environmental effects based on emission reduction technologies.
Subject(s)
Ammonia/metabolism , Environment , Animals , Animals, Domestic/metabolism , Humans , Nitrogen/metabolism , ScotlandABSTRACT
Bimonthly integrated measurements of NO2 and NH3 have been made over one year at distances up to 10 m away from the edges of roads across Scotland, using a stratified sampling scheme in terms of road traffic density and background N deposition. The rate of decrease in gas concentrations away from the edge of the roads was rapid, with concentrations falling by 90% within the first 10 m for NH3 and the first 15 m for NO2. The longer transport distance for NO2 reflects the production of secondary NO2 from reaction of emitted NO and O3. Concentrations above the background, estimated at the edge of the traffic lane, were linearly proportional to traffic density for NH3 (microg NH3 m(-3) = 1 x 10(-4) x numbers of cars per day), reflecting emissions from three-way catalysts. For NO2, where emissions depend strongly on vehicle type and fuel, traffic density was calculated in terms of 'car equivalents'; NO2 concentrations at the edge of the traffic lane were proportional to the number of car equivalents (microg NO2 m(-3) = 1 x 10(-4) x numbers of car equivalents per day). Although absolute concentrations (microg m(-3)) of NH3 were five times smaller than for NO2, the greater deposition velocity for NH3 to vegetation means that approximately equivalent amounts of dry N deposition to road side vegetation from vehicle emissions comes from NH3 and NO2. Depending on traffic density, the additional N deposition attributable to vehicle exhaust gases is between 1 and 15 kg N ha(-1) y(-1) at the edge of the vehicle lane, falling to 0.2-10 kg N ha(-1) y(-1) at 10 m from the edge of the road.
Subject(s)
Air Pollutants/analysis , Ammonia/analysis , Nitrogen Dioxide/analysis , Vehicle Emissions/analysis , Eutrophication , Motor Vehicles , Nitrous Acid/analysis , Scotland , SeasonsABSTRACT
1. Four new metabolites of pioglitazone were identified by liquid chromatography-mass spectrometry (LC-MS/MS) as being formed by hydroxylation (M-VII and M-VIII), opening of the thiazolidinedione ring (M-X) and by desaturation of the terminal ethyl side chain or tether ethoxy moiety (M-IX), respectively. The structure of one of the hydroxylated metabolites (M-VII) was confirmed by chemical modification using the Jones reaction. 2. Oxidative cleavage of the thiazolidinedione ring is a novel pathway not previously reported for pioglitazone. 3. The hydroxylated M-VII was detected in incubations with rat, dog and human liver and kidney microsomes, and in plasma from rats and dogs dosed orally with [(3)H]pioglitazone. 4. The carboxylic acid derivative of M-VII (M-V) and its taurine conjugate were the major radioactive components in dog bile.
Subject(s)
Thiazolidinediones/metabolism , Animals , Bile/metabolism , Chromatography, Liquid/methods , Dogs , Humans , Hydroxylation , Kidney/metabolism , Mass Spectrometry/methods , Microsomes/metabolism , Microsomes, Liver/metabolism , Oxidation-Reduction , Pioglitazone , Rats , Thiazolidinediones/blood , Thiazolidinediones/chemistry , Thiazolidinediones/urine , TritiumABSTRACT
An inter-comparison of techniques for long-term sampling of atmospheric ammonia (NH3) was conducted with a view to establishing a national network with > 50 sites. Key requirements were for: a low cost system, simplicity and durability to enable a postal exchange with local site operators, a precision of < +/- 20% for monthly sampling at expected NH3 concentrations of 1-2 micrograms m-3, a detection limit sufficient to resolve the small NH3 concentrations (< 0.2 microgram m-3) expected in remote parts of the UK, and a quantitative means to establish quality control. Five sampling methods were compared: A, a commercially available membrane diffusion tube (exposed in triplicate), with membranes removed immediately after sampling; B, the above method, with the membranes left in place until analysis; C, open-ended diffusion tubes (exposed with 4 replicates); D, a new active sampling diffusion denuder system; and E, an active sampling bubbler system. Method D consisted of two 0.1 m acid coated glass denuders in series with sampling at approximately 0.3 l min-1. These methods were deployed at 6 locations in the UK and the Netherlands and compared against reference estimates. Method D was the most precise and sensitive of the techniques compared, with a detection limit of < 0.1 microgram m-3. The bubbler provided a less precise estimate of NH3 concentration, and also suffered several practical drawbacks. The diffusion tubes were found to correlate with the reference at high concentrations (> 3 micrograms m-3), but were less precise and overestimated NH3 at smaller concentrations. Of the passive methods, A was the most precise and C the least precise. On the basis of the results, method D has been implemented in the national network, together with application of method A to explore spatial variability in regions with expected high NH3 concentrations.
Subject(s)
Air Pollutants/analysis , Environmental Monitoring/methods , Quaternary Ammonium Compounds/analysis , Cost Control , Diffusion , Membranes, Artificial , Specimen HandlingABSTRACT
The interaction of an 18-base cis-element in the 5'-untranslated region of human folate receptor (FR)-alpha mRNA with a cytosolic trans-factor protein is critical for the translation of FR (Sun, X.-L., and Antony, A. C. (1996) J. Biol. Chem. 271, 25539-25547). This trans-factor was isolated to apparent homogeneity as a 43- and 38-kDa doublet from human placenta using poly(U)-Sepharose, followed by preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electro-elution as major purification steps. Amino acid microsequencing of two cyanogen bromide-generated peptide fragments of the 43-kDa trans-factor revealed complete identity with 43-kDa heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1). Purified specific rabbit anti-hnRNP E1 peptide antibodies (generated against a synthetic oligopeptide that was not represented in microsequenced peptides of the trans-factor) also recognized the purified trans-factor on Western blots. Conversely, the 18-base FR RNA cis-element also bound hnRNP E1 protein on Northwestern blots. Moreover, a 19-base RNA cis-element in the 3'-untranslated region of 15-lipoxygenase mRNA that is known to bind hnRNP E1 also interacted with placental 43-kDa trans-factor. In addition, several murine tissues containing a hnRNP E1-related protein (also known as alphaCP-1) readily interacted with the 18-base FR RNA cis-element. Finally, anti-hnRNP E1 antibodies specifically inhibited translation of FR in vitro in a dose-dependent manner, and the antibody effect could be reversed in a dose-dependent manner by either purified trans-factor or hnRNP E1. Collectively, the data favor identity of the FR mRNA-binding trans-factor and hnRNP E1, confirm its critical role in the translation of FR, and highlight yet another role of multifunctional hnRNP E1 in eukaryotic mRNA regulation.
Subject(s)
Carrier Proteins/genetics , Placenta/metabolism , RNA, Messenger/metabolism , RNA-Binding Proteins/isolation & purification , Receptors, Cell Surface , Amino Acid Sequence , Base Sequence , DNA Primers , Female , Folate Receptors, GPI-Anchored , Heterogeneous-Nuclear Ribonucleoproteins , Humans , Molecular Sequence Data , RNA-Binding Proteins/chemistry , RNA-Binding Proteins/metabolism , Ribonucleoproteins/metabolismABSTRACT
UNLABELLED: Inotropes are often used to treat myocardial dysfunction shortly after cardiopulmonary bypass (CPB). beta-Adrenergic agonists improve contractility, in part by increasing cyclic adenosine monophosphate (cAMP) production, whereas phosphodiesterase type III inhibitors prevent its breakdown. CPB is associated with abnormalities at the beta-receptor level and diminished adenyl cyclase activity, both of which tend to decrease cAMP. These effects may be increased in the presence of preexisting myocardial dysfunction. We tested the hypothesis that inhibition of phosphodiesterase type III before global myocardial ischemia and pharmacologic arrest results in the preservation of intramyocardial cAMP concentration during CPB. Twenty adult patients undergoing coronary artery bypass grafting with CPB were studied. After CPB was instituted, a myocardial biopsy was obtained from the apex of the left ventricle. Patients were randomized to receive either placebo or milrinone (50 micro/kg) through the bypass pump 10 min before aortic cross-clamping. Another myocardial biopsy was performed adjacent to the left ventricular apex just before weaning from CPB. Myocardial cAMP concentration was determined by radioimmunoassay. Myocyte protein content was determined by the Bradford method by using a commercial kit. There were no significant demographic differences between the groups; however, patients in the Milrinone group had a lower left ventricular ejection fraction than placebo (41% +/- 13% vs 53% +/- 7%; P < 0.05). Patients who received milrinone had larger cAMP concentrations at the end of CPB compared with placebo (21 +/- 12.5 pmol/mg protein versus 12.8 +/- 2.2 pmol/mg protein; P < 0.05). The administration of milrinone before aortic cross-clamping is associated with increased intramyocardial cAMP concentration at the end of CPB. IMPLICATIONS: The administration of a single dose of milrinone before aortic cross-clamping resulted in significantly larger intramyocardial cyclic adenosine monophosphate concentration in myocardial biopsy specimens compared with controls.
Subject(s)
3',5'-Cyclic-AMP Phosphodiesterases/antagonists & inhibitors , Cardiopulmonary Bypass/adverse effects , Cyclic AMP/metabolism , Milrinone/therapeutic use , Myocardium/metabolism , Phosphodiesterase Inhibitors/therapeutic use , Aged , Aorta/physiology , Constriction , Cyclic Nucleotide Phosphodiesterases, Type 3 , Female , Hemodynamics/drug effects , Humans , Hypothermia, Induced , Intraoperative Period , Male , Middle AgedABSTRACT
As measures are implemented internationally to reduce SO2 and NOx emissions, attention is falling on the contribution of NH3 emissions to acidification, nitrogen eutrophication, and aerosol formation. In the U.K., a monitoring network has been established to measure the spatial distribution and long-term trends in atmospheric gaseous NH3 and aerosol NH4+. At the same time, an atmospheric chemistry and transport model, FRAME, has been developed with a focus on reduced nitrogen (NHx). The monitoring data are important to evaluate the model, while the model is essential for a more detailed spatial assessment. The national network is established with over 80 sampling locations. Measurements of NH3 and NH4+ (at up to 50 sites) have been made using a new low-cost denuder-filterpack system. Additionally, improved passive sampling methods for NH3 have been applied to explore local variability. The measurements confirm the high spatial variability of NH3 (annual means 0.06 to 11 microg NH3 m(-3)), consistent with its nature as a primary pollutant emitted from ground-level sources, while NH4+, being a slowly formed secondary product, shows much less spatial variability (0.14 to 2.4 mg NH4+ m(-3)). These features are reproduced in the FRAME model, which provides estimates at a 5-km level. Analysis of the underlying NH3 emission inventory shows that sheep emissions may have been underestimated and nonagricultural sources overestimated relative to emissions from cattle. The combination of model and measurements is applied to estimate spatial patterns of dry deposition to different vegetation types. The combined approach provides the basis to assess NHx responses across the U.K. to international emission controls.