Association analysis of sphingomyelinase 2 polymorphisms for the extrinsic type of atopic dermatitis in Koreans.
Explore the source record for details and available documents.
Asian People↗
Biomedical subjects
Eugene Kim
Publications and source records attributed to Eugene Kim.
Characterization of fine particle sources in the Great Smoky Mountains area.
A source apportionment study to characterize sources of fine particles in the Great Smoky Mountains area was conducted analyzing ambient PM(2.5) (particulate matter< or =2.5 microm in aerodynamic diameter) speciation data collected at a Interagency Monitoring of Protected Visual Environments (IMPROVE) monitoring site. A total of 1442 samples collected between March 1988 and December 2003 analyzed for 30 elemental species were analyzed with the application of the positive matrix factorization (PMF). Eight major sources were extracted: summer-high secondary sulfate (55%), carbon-rich secondary sulfate (16%), summer-low secondary sulfate (2%), gasoline vehicle emissions (13%), diesel emissions (1%), airborne soil (6%), industry (5%), and secondary nitrate (2%). The contributions from the carbon-rich secondary sulfate particles are likely a combination of local and regional influences of the biogenic as well as anthropogenic secondary particles. The compositional profiles for gasoline vehicle and diesel emissions are similar to those identified in other US areas. Backward trajectories indicate that the high impacts of airborne soil were likely caused by Asian and Saharan dust storms. This study would assist in the implementation plan development for attaining the air quality standards for PM(2.5), regional haze rule planning, and source-specific community epidemiology.
Air Pollutants↗
The novel cytokine p43 induces IL-12 production in macrophages via NF-kappaB activation, leading to enhanced IFN-gamma production in CD4+ T cells.
Recently, we determined that p43, an auxiliary factor of mammalian multiaminoacyl-tRNA synthetases, is secreted, and functions as a novel pleiotropic cytokine. In this study, we have attempted to characterize the effects of p43 on the generation of IL-12 in mouse macrophages. p43 was determined to induce significant IL-12 production from mouse macrophages in a dose-dependent manner. The stimulatory effect of p43 on the activation of IL-12p40 promoter was mapped to a region harboring an NF-kappaB binding site. The nuclear extracts from the p43-stimulated macrophages exhibited profound NF-kappaB DNA-binding activity, as determined by the EMSA. In addition, the p43-stimulated IL-12 induction and NF-kappaB DNA-binding activity were significantly suppressed by caffeic acid phenethyl ester and BAY11-7082, both inhibitors of NF-kappaB activation, indicating that p43 induced the production of IL-12 in macrophages mainly via the activation of NF-kappaB. Importantly, p43 increased the level of IFN-gamma production in the Ag-primed lymph node cells, but had no effect on IL-4 levels. The addition of a neutralizing anti-IL-12p40 mAb to the cell cultures resulted in a decrease of the production of p43-enhanced IFN-gamma by the keyhole limpet hemocyanin-primed lymph node cells. Furthermore, coincubation with p43-pretreated macrophages enhanced the production of IFN-gamma by the keyhole limpet hemocyanin-primed CD4+ T cells, thereby indicating that p43 may enhance IFN-gamma expression in CD4+ T cells via the induction of IL-12 production in macrophages. These results indicate that p43 may play an essential role in the development of the Th1 immune responses associated with cancer immunotherapy and protective immunity against intracellular pathogens.
Animals↗
PM source apportionment and health effects: 1. Intercomparison of source apportionment results.
During the past three decades, receptor models have been used to identify and apportion ambient concentrations to sources. A number of groups are employing these methods to provide input into air quality management planning. A workshop has explored the use of resolved source contributions in health effects models. Multiple groups have analyzed particulate composition data sets from Washington, DC and Phoenix, AZ. Similar source profiles were extracted from these data sets by the investigators using different factor analysis methods. There was good agreement among the major resolved source types. Crustal (soil), sulfate, oil, and salt were the sources that were most unambiguously identified (generally highest correlation across the sites). Traffic and vegetative burning showed considerable variability among the results with variability in the ability of the methods to partition the motor vehicle contributions between gasoline and diesel vehicles. However, if the total motor vehicle contributions are estimated, good correspondence was obtained among the results. The source impacts were especially similar across various analyses for the larger mass contributors (e.g., in Washington, secondary sulfate SE=7% and 11% for traffic; in Phoenix, secondary sulfate SE=17% and 7% for traffic). Especially important for time-series health effects assessment, the source-specific impacts were found to be highly correlated across analysis methods/researchers for the major components (e.g., mean analysis to analysis correlation, r>0.9 for traffic and secondary sulfates in Phoenix and for traffic and secondary nitrates in Washington. The sulfate mean r value is >0.75 in Washington.). Overall, although these intercomparisons suggest areas where further research is needed (e.g., better division of traffic emissions between diesel and gasoline vehicles), they provide support the contention that PM(2.5) mass source apportionment results are consistent across users and methods, and that today's source apportionment methods are robust enough for application to PM(2.5) health effects assessments.
Air Pollutants↗
Sources of fine particulate species in ambient air over lake Champlain Basin, VT.
This study is a part of an ongoing investigation of the types and locations of emission sources that contribute fine particulate air contaminants to Underhill, VT. The air quality monitoring data used for this study are from the Interagency Monitoring of Protected Visual Environments network for the period of 2001-2003 for the Underhill site. The main source-receptor modeling techniques used are the positive matrix factorization (PMF) and potential source contribution function (PSCF). This new study is intended as a comparison to a previous study of the 1988-1995 Underhill data that successfully revealed a total of 11 types of emission sources with significant contributions to this rural site. This new study has identified a total of nine sources: nitrate-rich secondary aerosol, wood smoke, East Coast oil combustion, automobile emission, metal working, soil/dust, sulfur-rich aerosol type I, sulfur-rich aerosol type II, and sea salt/road salt. Furthermore, the mass contributions from the PMF identified sources that correspond with sampling days with either good or poor visibility were analyzed to seek possible correlations. It has been shown that sulfur-rich aerosol type I, nitrate aerosol, and automobile emission are the most important contributors to visibility degradation. Soil/dust and sea salt/road salt also have an added effect.
Aerosols↗
Interpreting positive signs of the supraspinatus test in screening for torn rotator cuff.
The purpose of this study was to investigate the validity of the supraspinatus test as a screening test for detecting torn rotator cuff and to determine what its valuable positive signs were. Both the empty-can test and full-can test were performed on 200 shoulders diagnosed by magnetic resonance imaging (MRI)-and in some cases, surgical findings-to have full-thickness or partial-thickness torn rotator cuff s, or no tear in the rotator cuff . During the maneuver, the presence of pain or weakness or both pain and weakness were recorded as positive signs, and the distribution of these signs were analyzed according to the degree of tear. The predictive values were calculated in 2 ways by considering (1) only full-thickness tears as tears and (2) both full- and partial-thickness tears as tears. The 2 tests and the 2 ways of considering partial-thickness tears were compared. Pain and weakness were severity-dependent, and the empty-can test had a higher incidence of pain. The sensitivities of the 2 supraspinatus tests in all positive signs were higher when including partial-thickness tears in the tear group ; however, their specificities were higher when excluding partial-thickness tears. Both pain and weakness were interpretive for the supraspinatus test, and both tests were sensitive to full- and partial- thickness tears and specific for full-thickness tears.
Adult↗
CDK5 is a novel regulatory protein in PPARgamma ligand-induced antiproliferation.
Cyclin-dependent kinase 5 (Cdk5) is a member of the cyclin-dependent kinase family and has been studied mainly in the differentiation of post-mitotic neurons. The purpose of this study was to determine the presence of cdk5 expression and activity in colon cancer cells and to investigate its role in the regulation of PPARgamma ligand-induced antiproliferation. We observed that cdk5 protein levels and kinase activity were elevated in both HT-29 cells and human tumor tissue in comparison to decreased levels in normal colonic mucosa. To elucidate cdk5's role in PPARgamma ligand-induced antiproliferation of colon cancer cells, HT-29 cells were treated with ciglitazone. A dose- and time-dependent decrease in cell proliferation were observed after ciglitazone exposure, which correlated with a decrease in cdk5 protein expression and kinase activity. Importantly, these ciglitazone-induced antiproliferative changes were reversed when cdk5 was overexpressed. Although present, p35, the regulatory protein of cdk5, showed no significant changes in protein expression with the introduction of ciglitazone. This is the first report of cdk5/p35 expression and kinase activity in colon cancer cells, which is associated with ciglitazone-induced antiproliferation in HT-29 cells.
Adaptor Proteins, Signal Transducing↗
PM source apportionment and health effects: 2. An investigation of intermethod variability in associations between source-apportioned fine particle mass and daily mortality in Washington, DC.
Source apportionment may be useful in epidemiological investigation of PM health effects, but variations and options in these methods leave uncertainties. An EPA-sponsored workshop investigated source apportionment and health effects analyses by examining the associations between daily mortality and the investigators' estimated source-apportioned PM(2.5) for Washington, DC for 1988-1997. A Poisson Generalized Linear Model (GLM) was used to estimate source-specific relative risks at lags 0-4 days for total non-accidental, cardiovascular, and cardiorespiratory mortality adjusting for weather, seasonal/temporal trends, and day-of-week. Source-related effect estimates and their lagged association patterns were similar across investigators/methods. The varying lag structure of associations across source types, combined with the Wednesday/Saturday sampling frequency made it difficult to compare the source-specific effect sizes in a simple manner. The largest (and most significant) percent excess deaths per 5-95(th) percentile increment of apportioned PM(2.5) for total mortality was for secondary sulfate (variance-weighted mean percent excess mortality=6.7% (95% CI: 1.7, 11.7)), but with a peculiar lag structure (lag 3 day). Primary coal-related PM(2.5) (only three teams) was similarly significantly associated with total mortality with the same 3-day lag as sulfate. Risk estimates for traffic-related PM(2.5), while significant in some cases, were more variable. Soil-related PM showed smaller effect size estimates, but they were more consistently positive at multiple lags. The cardiovascular and cardiorespiratory mortality associations were generally similar to those for total mortality. Alternative weather models generally gave similar patterns, but sometimes affected the lag structure (e.g., for sulfate). Overall, the variations in relative risks across investigators/methods were found to be much smaller than those across estimated source types or across lag days for these data. This consistency suggests the robustness of the source apportionment in health effects analyses, but remaining issues, including accuracy of source apportionment and source-specific sensitivity to weather models, need to be investigated.
Air Pollutants↗
PM source apportionment and health effects. 3. Investigation of inter-method variations in associations between estimated source contributions of PM2.5 and daily mortality in Phoenix, AZ.
As part of an EPA-sponsored workshop to investigate the use of source apportionment in health effects analyses, the associations between the participant's estimated source contributions of PM(2.5) for Phoenix, AZ for the period from 1995-1997 and cardiovascular and total nonaccidental mortality were analyzed using Poisson generalized linear models (GLM). The base model controlled for extreme temperatures, relative humidity, day of week, and time trends using natural spline smoothers. The same mortality model was applied to all of the apportionment results to provide a consistent comparison across source components and investigators/methods. Of the apportioned anthropogenic PM(2.5) source categories, secondary sulfate, traffic, and copper smelter-derived particles were most consistently associated with cardiovascular mortality. The sources with the largest cardiovascular mortality effect size were secondary sulfate (median estimate=16.0% per 5th-to-95th percentile increment at lag 0 day among eight investigators/methods) and traffic (median estimate=13.2% per 5th-to-95th percentile increment at lag 1 day among nine investigators/methods). For total mortality, the associations were weaker. Sea salt was also found to be associated with both total and cardiovascular mortality, but at 5 days lag. Fine particle soil and biomass burning factors were not associated with increased risks. Variations in the maximum effect lag varied by source category suggesting that past analyses considering only single lags of PM(2.5) may have underestimated health impact contributions at different lags. Further research is needed on the possibility that different PM(2.5) source components may have different effect lag structure. There was considerable consistency in the health effects results across source apportionments in their effect estimates and their lag structures. Variations in results across investigators/methods were small compared to the variations across source categories. These results indicate reproducibility of source apportionment results across investigative groups and support applicability of these methods to effects studies. However, future research will also need to investigate a number of other important issues including accuracy of results.
Air Pollutants↗
Sources of fine particles in a rural midwestern U.S. area.
Ambient PM2.5 (particulate matter < or = 2.5 microm in aerodynamic diameter) samples collected at a rural monitoring site in Bondville, IL on every third day using Interagency Monitoring of Protected Visual Environments (IMPROVE) sampler were analyzed through the application of the positive matrix factorization (PMF). The particulate carbon fractions were obtained from the thermal optical reflectance method that divides particulate carbon into four organic carbon, pyrolyzed organic carbon (OP), and three elemental carbon fractions. A total of 257 samples collected between March 2001 and May 2003 analyzed for 35 species were used and eight sources were identified: summer-high secondary sulfate aerosol (40%), secondary nitrate aerosol (32%), gasoline vehicle (9%), OP-high secondary sulfate aerosol (7%), selenium-high secondary sulfate aerosol (4%), airborne soil (4%), aged sea salt (2%), and diesel emissions (2%). The compositional profiles for gasoline vehicle and diesel emissions are similar to those estimated in other U.S. areas. Backward trajectories indicate that the highly elevated airborne soil impacts were likely caused by Asian and Saharan dust storms. Potential source contribution function analyses show the potential source areas and pathways of secondary sulfate aerosols, especially the regional influences of the biogenic as well as anthropogenic secondary aerosol.
Air Pollutants↗
Spatial variability of fine particle mass, components, and source contributions during the regional air pollution study in St. Louis.
Community time-series epidemiology typically uses either 24-hour integrated particulate matter (PM) concentrations averaged across several monitors in a city or data obtained at a central monitoring site to relate PM concentrations to human health effects. If the day-to-day variations in 24-hour integrated concentrations differ substantially across an urban area (i.e., daily measurements at monitors at different locations are not highly correlated), then there is a significant potential for exposure misclassification in community time-series epidemiology. If the annual average concentration differs across an urban area, then there is a potential for exposure misclassification in epidemiologic studies that use annual averages (or multi-year averages) as an index of exposure across different cities. The spatial variability in PM2.5 (particulate matter < or = 2.5 microm in aerodynamic diameter), its elemental components, and the contributions from each source category at 10 monitoring sites in St. Louis, Missouri were characterized using the ambient PM2.5 compositional data set of the Regional Air Pollution Study (RAPS) based on the Regional Air Monitoring System (RAMS) conducted between 1975 and 1977. Positive matrix factorization (PMF) was applied to each ambient PM2.5 compositional data set to estimate the contributions from the source categories. The spatial distributions of components and source contributions to PM2.5 at the 10 sites were characterized using Pearson correlation coefficients and coefficients of divergence. Sulfur and PM2.5 are highly correlated elements between all of the site pairs Although the secondary sulfate is the most highly correlated and shows the smallest spatial variability, there is a factor of 1.7 difference in secondary sulfate contributions between the highest and lowest site on average. Motor vehicles represent the next most highly correlated source component. However, there is a factor of 3.6 difference in motor vehicle contributions between the highest and lowest sites. The contributions from point source categories are much more variable. For example, the contributions from incinerators show a difference of a factor of 12.5 between the sites with the lowest and highest contributions. This study demonstrates that the spatial distributions of elemental components of PM2.5 and contributions from source categories can be highly heterogeneous within a given airshed and thus, there is the potential for exposure misclassification when a limited number of ambient PM monitors are used to represent population-average ambient exposures.
Air Pollutants↗
Regulatory mechanisms and their therapeutic implications of interleukin-12 production in immune cells.
Studies with neutralizing anti-interleukin (IL)-12 antibodies and IL-12-deficient mice have suggested that endogenous IL-12 plays an important role in the normal host defense against infection by a variety of intracellular microorganisms. However, IL-12 also appears to play a central role in the pathogenesis of autoimmune diseases such as multiple sclerosis or rheumatic arthritis. Therefore, it is crucial to understand how IL-12 is produced and its production is regulated at the molecular level. IL-12 production is differentially regulated through multiple pathways, which can be classified as follows: nuclear factor-kappaB (NF-kappaB) and other transcription factors, p38 mitogen-activated protein (MAP) kinase, cyclic adenosine monophosphate (cyclic AMP)-modulating molecules, cell membrane ion channels and pumps, nitric oxide (NO), and receptors. In this review we describe the regulatory mechanisms of IL-12 production in immune cells and also some agents to control IL-12 production for the treatment of immune-related diseases.
Animals↗
Inhibition of interleukin-12 production in mouse macrophages by hydroquinone, a reactive metabolite of benzene, via suppression of nuclear factor-kappaB binding activity.
Exposure to cigarette smoke is known to increase the risk of the development of allergic disease associated with T helper type 2 (Th2)-mediated immune responses. IL-12 is known to suppress Th2 responses. In this study we investigated the effects of hydroquinone (HQ), a major metabolite of benzene present in large quantities in cigarette tar, on the production of IL-12 from mouse macrophages stimulated with lipopolysaccharide (LPS). HQ potently inhibited the LPS-induced IL-12 production in both primary mouse macrophages and RAW164.7 monocytic cells in a dose-dependent manner. The effect of HQ on IL-12 p40 promoter activation was analyzed by transfecting RAW264.7 monocytic cells with p40 promoter/luciferase constructs. The repressive effect mapped to a region in the p40 promoter containing a binding site for nuclear factor-kappaB (p40-kappaB). Furthermore, activation of macrophages by LPS resulted in markedly enhanced binding activity to the kappaB site, which significantly decreased upon addition of HQ. Pre-incubation with HQ significantly prevented degradation of IkappaB protein in LPS-stimulated macrophage cells, indicating that HQ suppressed NF-kappaB binding activity by inhibiting the degradation of IkappaB protein. These findings suggest that HQ may, at least in part, enhance allergic immune responses by inhibiting the production of IL-12 in macrophages.
Animals↗
Characteristics of an isolated greater tuberosity fracture of the humerus.
BACKGROUND: Most classification systems tend to include isolated greater tuberosity fractures in the group of proximal humeral fractures. The purpose of this study was to elucidate demographic differences between isolated greater tuberosity fractures and the other proximal humeral fractures. METHODS: Altogether, 610 proximal humeral fractures were divided into isolated greater tuberosity fractures of the proximal humerus (group I) and all other proximal humeral fractures (group II). The two groups were analyzed according to their incidence, age and sex distribution, presence of dislocation, and associated chronic medical problems. RESULTS: Group I comprised 18.9% and group II 81.1% off all fractures. The mean age of group I was 42.8 years, and that of group II was 54.2 years. Of the 115 (67.8%) patients in group I, 78 (67.8%) were male. In contrast, most of the group II patients were female (332/495, 67.1%). A higher incidence of glenohumeral dislocation occurred in group I (6.9%) than in group II (3.4%). Of the 495 group II patients, 175 (35.4%) had medical problems, including endocrine, cardiovascular, pulmonary, hepatic, and renal disease, whereas only 15 of the 115 (13%) patients in group I had such problems. CONCLUSIONS: Patients with isolated greater tuberosity fractures of the proximal humerus were different demographically, and their treatment and classification should be considered separately from that for other proximal humeral fractures.
Adolescent↗
Compartment syndrome after compression sclerotherapy.
Acute limb compartment syndrome is a condition in which raised pressure within a closed fascial space reduces capillary perfusion below a level necessary for tissue viability. Although it is a rare but potentially disastrous complication of orthopedic injury to the extremities, it may occur spontaneously without a history of trauma, and any insult that tends to increase resistance to flow in the capillary bed in any anatomical situation may result in a compartment syndrome. We report an extremely rare case of compartment syndrome following compression sclerotherapy.
Adult↗
Ciglitazone-induced p27 gene transcriptional activity is mediated through Sp1 and is negatively regulated by the MAPK signaling pathway.
We have previously demonstrated that the PPARgamma ligand, ciglitazone, increases p27kip1 protein levels in HT-29 colon cancer cells through both inhibition of proteasome associated degradation and activation of transcriptional activity. [F. Chen, L.E. Harrison, Cell Signal. 17 (2005) 809] The purpose of this investigation was to further elucidate the mechanism of ciglitazone-induced activation of p27 gene transcription. We observed that the region -774/-462 of the p27 promoter plays a key role in ciglitazone-induced gene transcriptional activity and this region contains two Sp1 binding sites. When the p27PF-luc reporter was co-transfected with Sp1 expression plasmids, ciglitazone-induced p27PF-luc activity significantly increased, while mithramycin A, a Sp1 inhibitor, was able to abrogate its effects. Ciglitazone exposure increased both Sp1 protein expression and Sp1-DNA binding, which was also associated with a decrease of Erk1/2 phosphorylation. A similar increase of Sp1-DNA binding was observed when phosphorylation of Erk1/2 was inhibited by pretreatment with the MAP kinase inhibitor, U0126. In addition, a significant increase of p27PF-luc reporter luciferase activity was noted after MAP kinase inhibition, which could be abolished with co-treatment with mithramycin A. Based on these data, we postulate that ciglitazone induces p27 gene transcription through increased Sp1 binding to its promoter region, which in turn is mediated through increased Sp1 protein levels and decreased inhibitory regulation by the MAP kinase pathway.
Binding Sites↗
Association between particulate matter and emergency room visits, hospital admissions and mortality in Spokane, Washington.
There is conflicting evidence regarding the association between different size fractions of particulate matter (PM) and cardiac and respiratory morbidity and mortality. We investigated the short-term associations of four size fractions of particulate matter (PM(1), PM(2.5), PM(10), and PM(10-2.5)) and carbon monoxide with hospital admissions and emergency room (ER) visits for respiratory and cardiac conditions and mortality in Spokane, Washington. We used a log-linear generalized linear model to compare daily averages of PM and carbon monoxide with daily counts of the morbidity and mortality outcomes from January 1995 to June 2001. We examined pollution lags ranging from 0 to 3 days and compared our results to a similar log-linear generalized additive model. Effect estimates tended to be smaller and have larger standard errors for the generalized linear model. Overall, we saw no association with respiratory ER visits and any size fraction of PM. However, there was a suggestion of greater respiratory effect from fine PM when compared to coarse fraction. Carbon monoxide was associated with both all respiratory ER visits and visits for asthma at the 3-day lag. We feel that carbon monoxide may be serving as a marker for combustion-derived pollutants, which is one large component of the diverse air pollutant mixture. We also found no association with any size fraction of PM or CO with cardiac hospital admissions or mortality at the 0- to 3-day lag. We found no consistent associations between any size fraction of PM and cardiac or respiratory ER visits or hospital admissions.
Air Pollutants↗
Investigation of sources of atmospheric aerosol at a hot spot area in Dhaka, Bangladesh.
Samples of fine and coarse fractions of airborne particulate matter were collected at the Farm Gate area in Dhaka from July 2001 to March 2002. Dhaka is a hot spot area with very high pollutant concentrations because of the proximity of major roadways. The samples were collected using a "Gent" stacked filter unit in two fractions of 0- to 2.2-microm and 2.2- to 10-microm sizes. The samples were analyzed for elemental concentrations by particle-induced X-ray excitation (PIXE) and for black carbon by reflectivity methods, respectively. The data were analyzed by positive matrix factorization (PMF) to identify the possible sources of atmospheric aerosols in this area. Six sources were found for both the coarse and fine PM fractions. The data sets were also analyzed by an expanded model to explore additional sources. Seven and six factors were obtained for coarse and fine PM fractions, respectively, in these analyses. The identified sources are motor vehicle, soil dust, emissions from construction activities, sea salt, biomass burning/brick kiln, resuspended/fugitive Pb, and two-stroke engines. From the expanded modeling, approximately 50% of the total PM2.2 mass can be attributed to motor vehicles, including two-stroke engine vehicle in this hot spot in Dhaka, whereas the PMF modeling indicates that 45% of the total PM2.2 mass is from motor vehicles. The PMF2 and expanded models could resolve approximately 4% and 3% of the total PM2.2 mass as resuspended/fugitive Pb, respectively. Although, Pb has been eliminated from gasoline in Bangladesh since July 1999, there still may be substantial amounts of accumulated lead in the dust near roadways as well as fugitive Pb emissions from battery reclaimation and other industries. Soil dust is the largest component of the coarse particle fraction (PM2.2-10) accounting for approximately 71% of the total PM2.2-10 mass in the expanded model, whereas from the PMF modeling, the dust (undifferentiated) contribution is approximately 49%.
Aerosols↗