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PubMed1995

East German uranium miners (Wismut)--exposure conditions and health consequences.

Underground uranium mining was performed in East Germany after World War II on a large scale. East Germany was the main supplier of uranium for the Soviet Union. This review gives a historical summary and describes the broad spectrum of exposure to potential health hazards and the health consequences. Working conditions were very poor during the postwar years from approximately 1946-1955: there was drilling with air floating and a lack of forced ventilation. Dust levels were very high and there was a significant inhalative incorporation of alpha-radiating substances, mostly from short-lived radon progeny. However, long-lived alpha-radiating substances such as uranium-238 contributed considerably to the radiation dose. There was also exposure to toxic chemicals, such as arsenic (in some mines) or crystalline silica, and a variety of other health hazards. From approximately 1956-1970, mining conditions improved: there was drilling with the addition of water and forced ventilation of the mines. As of approximately 1970, compliance with rules of industrial hygiene and international standards of radiation protection was evident. In 1990, uranium production was generally stopped. To date, more than 5,000 cases of bronchial carcinoma are accepted as compensable occupational diseases and more are expected. The extensive data from Wismut uranium mining could improve our understanding of a complex exposure situation resulting in a variety of health impairments other than lung cancer.

Germany↗
PubMed2004

iProLINK: an integrated protein resource for literature mining.

The exponential growth of large-scale molecular sequence data and of the PubMed scientific literature has prompted active research in biological literature mining and information extraction to facilitate genome/proteome annotation and improve the quality of biological databases. Motivated by the promise of text mining methodologies, but at the same time, the lack of adequate curated data for training and benchmarking, the Protein Information Resource (PIR) has developed a resource for protein literature mining--iProLINK (integrated Protein Literature INformation and Knowledge). As PIR focuses its effort on the curation of the UniProt protein sequence database, the goal of iProLINK is to provide curated data sources that can be utilized for text mining research in the areas of bibliography mapping, annotation extraction, protein named entity recognition, and protein ontology development. The data sources for bibliography mapping and annotation extraction include mapped citations (PubMed ID to protein entry and feature line mapping) and annotation-tagged literature corpora. The latter includes several hundred abstracts and full-text articles tagged with experimentally validated post-translational modifications (PTMs) annotated in the PIR protein sequence database. The data sources for entity recognition and ontology development include a protein name dictionary, word token dictionaries, protein name-tagged literature corpora along with tagging guidelines, as well as a protein ontology based on PIRSF protein family names. iProLINK is freely accessible at http://pir.georgetown.edu/iprolink, with hypertext links for all downloadable files.

Computational Biology↗
PubMedDate not supplied

Does coal mine dust present a risk for lung cancer? A case-control study of U.S. coal miners.

This paper evaluates the relationship between the risk of lung cancer mortality and coal mine dust exposure under control by cigarette smoking status. Two case-control studies based on 317 white male lung cancer mortality cases are presented. A one-to-one matched-case design allows examination of the risk of coal mine dust exposure and cigarette smoking. A two-to-one matched-case design was employed to examine the lung cancer risk of coal mine dust exposure independent of cigarette smoking. Based upon these data, no evidence of a coal mine dust exposure-lung cancer risk was found, although the expected increased risk for lung cancer in cigarette smokers was observed. There was no evidence of an interactive effect between cigarette smoking and coal mine dust exposure.

Coal Mining↗
PubMed2000

Distribution, speciation, and transport of mercury in stream-sediment, stream-water, and fish collected near abandoned mercury mines in southwestern Alaska, USA.

Concentrations of total Hg, Hg (II), and methylmercury were measured in stream-sediment, stream-water, and fish collected downstream from abandoned mercury mines in southwestern Alaska to evaluate environmental effects to surrounding ecosystems. These mines are found in a broad belt covering several tens of thousands of square kilometers, primarily in the Kuskokwim River basin. Mercury ore is dominantly cinnabar (HgS), but elemental mercury (Hg degrees) is present in ore at one mine and near retorts and in streams at several mine sites. Approximately 1400 t of mercury have been produced from the region, which is approximately 99% of all mercury produced from Alaska. These mines are not presently operating because of low prices and low demand for mercury. Stream-sediment samples collected downstream from the mines contain as much as 5500 microg/g Hg. Such high Hg concentrations are related to the abundance of cinnabar, which is highly resistant to physical and chemical weathering, and is visible in streams below mine sites. Although total Hg concentrations in the stream-sediment samples collected near mines are high, Hg speciation data indicate that concentrations of Hg (II) are generally less than 5%, and methylmercury concentrations are less than 1% of the total Hg. Stream waters below the mines are neutral to slightly alkaline (pH 6.8-8.4), which is a result of the insolubility of cinnabar and the lack of acid-generating minerals such as pyrite in the deposits. Unfiltered stream-water samples collected below the mines generally contain 500-2500 ng/l Hg; whereas, corresponding stream-water samples filtered through a 0.45-microm membrane contain less than 50 ng/l Hg. These stream-water results indicate that most of the Hg transported downstream from the mines is as finely-suspended material rather than dissolved Hg. Mercury speciation data show that concentrations of Hg (II) and methylmercury in stream-water samples are typically less than 22 ng/l, and generally less than 5% of the total Hg. Muscle samples of fish collected downstream from mines contain as much as 620 ng/g Hg (wet wt.), of which 90-100% is methylmercury. Although these Hg concentrations are several times higher than that in fish collected from regional baseline sites, the concentration of Hg in fish is below the 1000 ng/g action level for edible fish established by the US Food and Drug Administration (FDA). Salmon contain less than 100 ng/g Hg, which are among the lowest Hg contents observed for fish in the study, and well below the FDA action level.

Alaska↗
PubMed1994

The assessment of exposure in terms of fibres.

The membrane filter (MF) method for evaluating asbestos fibre concentrations was introduced in the 1960s. Before that time the midget impinger (MI) was used in North America, while the long running (LRTP) and regular thermal precipitator (TP) were used in the U.K. All studies from which estimates of long-term health risks can be derived (i.e. those with individual cumulative lifetime exposure estimates) were based on the now obsolete methods. The reliability of converting these indices of exposure to MF equivalent concentrations was reviewed. It was concluded that no overall single factor could be derived for the Quebec mining and milling industry. However, it has been possible to derive conversion factors at the individual mill and work area level. Applying these in one Quebec mortality study analysis based on all jobs held by persons in the cohort gave an overall MF/MI ratio of 3.6. An examination of the confidence intervals surrounding the Quebec data, ratios derived for other chrysotile mines by other investigators, and measurements of fibre concentrations in the 1970s suggest that this was probably not unreasonable. Side-by-side and other measurements were used to convert MI concentrations in the U.S. textile industry to MF fibre concentrations. While conversions involve considerable uncertainty, independent measurements of fibres in the lung tissues of workers from the U.S. textile plant and Quebec mills show that in lungs the ratios of the concentrations of chrysotile to those of tremolite are quite consistent with the ratio of assessed exposures to these fibres in the two industries. There is an apparently higher risk of mesothelioma in one Quebec mining area (Thetford Mines) than in another (Asbestos). A high concentration of fibrous tremolite has been found in the lungs of workers in Thetford. A method of evaluating the extent to which mesothelioma risk in the chrysotile mining industry might be explained by tremolite exposures was proposed. The slope of the lung cancer dose-response relationship for the textile industry is approximately 50 times that for the mining and milling industry. Available data on the length distributions of fibres from Quebec mines and mills (up to 5% > 5 microns) and the Charleston textile plant (up to 21% > 5 microns) and some marginal indication of longer fibres in tissues from Charleston workers suggest that further work specifically addressing differences in the size distributions of long fibres in these industries is needed.

Asbestos, Serpentine↗
PubMed2005

A compendium of signals and responses triggered by prodeath and prosurvival cytokines.

Cell-signaling networks consist of proteins with a variety of functions (receptors, adaptor proteins, GTPases, kinases, proteases, and transcription factors) working together to control cell fate. Although much is known about the identities and biochemical activities of these signaling proteins, the ways in which they are combined into networks to process and transduce signals are poorly understood. Network-level understanding of signaling requires data on a wide variety of biochemical processes such as posttranslational modification, assembly of macromolecular complexes, enzymatic activity, and localization. No single method can gather such heterogeneous data in high throughput, and most studies of signal transduction therefore rely on series of small, discrete experiments. Inspired by the power of systematic datasets in genomics, we set out to build a systematic signaling dataset that would enable the construction of predictive models of cell-signaling networks. Here we describe the compilation and fusion of approximately 10,000 signal and response measurements acquired from HT-29 cells treated with tumor necrosis factor-alpha, a proapoptotic cytokine, in combination with epidermal growth factor or insulin, two prosurvival growth factors. Nineteen protein signals were measured over a 24-h period using kinase activity assays, quantitative immunoblotting, and antibody microarrays. Four different measurements of apoptotic response were also collected by flow cytometry for each time course. Partial least squares regression models that relate signaling data to apoptotic response data reveal which aspects of compendium construction and analysis were important for the reproducibility, internal consistency, and accuracy of the fused set of signaling measurements. We conclude that it is possible to build self-consistent compendia of cell-signaling data that can be mined computationally to yield important insights into the control of mammalian cell responses.

Amino Acid Sequence↗
PubMed1993

Monitoring genotoxic exposure in uranium miners.

Recent data from deep uranium mines in Czechoslovakia indicated that in addition to radon daughter products, miners are also exposed to chemical mutagens. Mycotoxins were identified as a possible source of mutagenicity present in the mines. Various methods of biomonitoring were used to examine three groups of miners from different uranium mines. Cytogenetic analysis of peripheral lymphocytes, unscheduled DNA synthesis (UDS) in lymphocytes, and lipid peroxidation (LPO) in both plasma and lymphocytes were studied on 66 exposed miners and 56 controls. Throat swabs were taken from 116 miners and 78 controls. Significantly increased numbers of aberrant cells were found in all groups of miners, as well as decreased UDS values in lymphocytes and increased LPO plasma levels in comparison to controls. Molds were detected in throat swabs from 27% of miners, and 58% of these molds were embryotoxic. Only 5% of the control samples contained molds and none of them was embryotoxic. The following mycotoxins were isolated from miners' throat swab samples: rugulosin, sterigmatocystin, mycophenolic acid, brevianamid A, citreoviridin, citrinin, penicilic acid, and secalonic acid. These data suggest that mycotoxins are a genotoxic factor affecting uranium miners.

Adult↗
PubMed2000

An improved inventory of methane emissions from coal mining in the United States.

Past efforts to estimate methane emissions from underground mines, surface mines, and other coal mine operations have been hampered, to different degrees, by a lack of direct emissions data. Direct measurements have been completely unavailable for several important coal mining operations. A primary goal of this study was to collect new methane emissions measurements and other data for the most poorly characterized mining operations and use these data to develop an improved methane emission inventory for the U.S. coal mining industry. This required the development and verification of measurement methods for surface mines, coal handling operations, and abandoned underground mines and the use of these methods at about 30 mining sites across the United States. Although the study's focus was on surface mines, abandoned underground mines, and coal handling operations, evaluations were also conducted to improve our understanding of underground mine emission trends and to develop improved national data sets of coal properties. Total U.S. methane emissions are estimated to be 4.669 million tons, and as expected, emissions from underground mine ventilation and methane drainage systems dominate (74% of the total emissions). On the other hand, emissions from coal handling, abandoned underground mines, and surface mines are significant, and collectively they represent approximately 26% of the total emissions.

Air Pollutants, Occupational↗
PubMed2006

Towards the integration of spatially and temporally resolved murine gene expression databases.

Several large-scale projects are evaluating gene expression in the mouse brain, both spatially and temporally. These range from projects that cover a broad spectrum of genes and developmental stages to those with high-spatial resolution and gene coverage but for only a single developmental stage. Each project contains its own self-consistent data set and tools for analysis and mining. Preliminary efforts are under way to construct tools and an infrastructure with which the data from across these different projects can be statistically pooled and analyzed. However, many obstacles remain, and these must be addressed and overcome soon if we are to unify the data sets, otherwise the preliminary efforts will be wasted. Here, the various projects for collecting and mining this information are reviewed, some challenges in data set comparisons are discussed, and some basic proposals are made for overcoming the challenges.

Animals↗
PubMed2006

A methodology for global validation of microarray experiments.

BACKGROUND: DNA microarrays are popular tools for measuring gene expression of biological samples. This ever increasing popularity is ensuring that a large number of microarray studies are conducted, many of which with data publicly available for mining by other investigators. Under most circumstances, validation of differential expression of genes is performed on a gene to gene basis. Thus, it is not possible to generalize validation results to the remaining majority of non-validated genes or to evaluate the overall quality of these studies. RESULTS: We present an approach for the global validation of DNA microarray experiments that will allow researchers to evaluate the general quality of their experiment and to extrapolate validation results of a subset of genes to the remaining non-validated genes. We illustrate why the popular strategy of selecting only the most differentially expressed genes for validation generally fails as a global validation strategy and propose random-stratified sampling as a better gene selection method. We also illustrate shortcomings of often-used validation indices such as overlap of significant effects and the correlation coefficient and recommend the concordance correlation coefficient (CCC) as an alternative. CONCLUSION: We provide recommendations that will enhance validity checks of microarray experiments while minimizing the need to run a large number of labour-intensive individual validation assays.

3T3-L1 Cells↗
PubMed2002

Chemometric contributions to the evolution of metabonomics: mathematical solutions to characterising and interpreting complex biological NMR spectra.

The pharmaceutical industry has embraced emerging technologies such as genomics, proteomics and metabonomics over the past decade with a view to minimizing attrition and expanding drug development pipelines. Metabonomic technology, based on the multivariate analysis of complex biological profiles generated from spectroscopic instruments, has enabled the construction of successful expert systems for toxicity screening and disease diagnosis. Here we describe the evolution of chemometric and bioinformatic methodologies to accommodate the multi- and megavariate data generated by high resolution NMR spectroscopy of biofluids, tissues and cell cultures and explore their potential role in mining, modeling and predicting metabolic data.

Animals↗
PubMed2001

Mantle flow beneath a continental strike-slip fault: postseismic deformation after the 1999 Hector Mine earthquake.

Two recent large earthquakes in the Mojave Desert, California-the magnitude 7.3 1992 Landers and magnitude 7.1 1999 Hector Mine earthquakes-have each been followed by elevated crustal strain rates over periods of months and years. Geodetic data collected after the Hector Mine earthquake exhibit a temporally decaying horizontal velocity field and a quadrant uplift pattern opposite to that expected for localized shear beneath the earthquake rupture. We interpret the origin of this accelerated crustal deformation to be vigorous flow in the upper mantle in response to the stress changes generated by the earthquake. Our results suggest that transient flow in the upper mantle is a fundamental component of the earthquake cycle and that the lower crust is a coherent stress guide coupling the upper crust with the upper mantle.

Journal Article↗
PubMed2003

Prioritizing abandoned coal mine reclamation projects within the contiguous United States using geographic information system extrapolation.

Coal mine reclamation projects are very expensive and require coordination of local and federal agencies to identify resources for the most economic way of reclaiming mined land. Location of resources for mine reclamation is a spatial problem. This article presents a methodology that allows the combination of spatial data on resources for the coal mine reclamation and uses GIS analysis to develop a priority list of potential mine reclamation sites within contiguous United States using the method of extrapolation. The extrapolation method in this study was based on the Bark Camp reclamation project. The mine reclamation project at Bark Camp, Pennsylvania, USA, provided an example of the beneficial use of fly ash and dredged material to reclaim 402,600 sq mi of a mine abandoned in the 1980s. Railroads provided transportation of dredged material and fly ash to the site. Therefore, four spatial elements contributed to the reclamation project at Bark Camp: dredged material, abandoned mines, fly ash sources, and railroads. Using spatial distribution of these data in the contiguous United States, it was possible to utilize GIS analysis to prioritize areas where reclamation projects similar to Bark Camp are feasible. GIS analysis identified unique occurrences of all four spatial elements used in the Bark Camp case for each 1 km of the United States territory within 20, 40, 60, 80, and 100 km radii from abandoned mines. The results showed the number of abandoned mines for each state and identified their locations. The federal or state governments can use these results in mine reclamation planning.

Carbon↗
PubMed2003

Fitting the two-stage model of carcinogenesis to nested case-control data on the Colorado Plateau uranium miners: dependence on data assumptions.

This paper investigates some problems with the Colorado Plateau uranium miners cohort when fitting the mechanistic model of carcinogenesis of Moolgavkar et al. (MVK model) to nested case-control data for lung cancers. The influence of data for hard rock mining and work histories on the model fitting is examined and found to be highly influential. The question of selecting the most appropriate number of controls per case is also considered. Analyses were carried out assuming that the hard rock mining exposure occurred prior to all other work histories and that miners received no exposure between work histories. The use of less than 15 controls per case was found to seriously restrict the quality of fit of the models. The best fitting, most reliable model contained linear effects of radon exposure on the first mutation rate, the rate of differentiation, and the rate of death of the intermediate cells. An effect of smoking on the growth of the intermediate cells was also included in the model. It is concluded that owing to the complexity of the MVK model and the limited amount of information in this dataset, the reliability of the Colorado Plateau dataset for fitting this type of model, particularly in a case-control format, is questionable.

Case-Control Studies↗
PubMedDate not supplied

Discovery of a new focus of human onchocerciasis in central Brazil.

An autochthonous case of human onchocerciasis was reported 13 years ago in the town of Minaçu, northern Goiás (Brazil), but a subsequent survey of the population using the traditional technique of examining skin biopsies with the light microscope failed to detect other cases. Recent surveys using more sensitive diagnostic techniques (serodiagnosis, DNA probes, Mazzotti test) that are detailed in this paper revealed the presence of other cases of the disease in Minaçu, the nearby town of Formoso and at the Buracão gold mine near Paranã. The data show that transmission of the disease has occurred to local people living in town and on farms and that gold miners (garimpeiros) are a likely source of infection.

Adolescent↗
PubMed2000

pH-dependent toxicity of copper and uranium to a tropical freshwater alga (Chlorella sp.).

Copper (Cu) and uranium (U) are of potential ecotoxicological concern to tropical freshwater organisms in northern Australia as a result of mining activity. No local data on the toxicity of these metals to tropical freshwater algae are currently available. The aim of this study was to investigate the effect of pH (5.7 and 6.5) on the toxicity of Cu and U to the green alga Chlorella sp. in a synthetic softwater representative of fresh surface waters in sandy-streams of tropical northern Australia. The effects of Cu and U on algal growth (cell division) rate after a 72-h exposure were determined. Intracellular and extracellular (membrane-bound) metal concentrations at the two selected pH values were also compared. Based on the 72-h minimum detectable effect concentrations (MDEC), Chlorella sp. was approximately 20-fold more sensitive to Cu (0.7 and 1.4 µg l(-1) at pH 6.5 and 5.7, respectively) than U (13 and 34 µg l(-1) at pH 6.5 and 5.7, respectively), and more sensitive than other Australian tropical freshwater organisms. The toxicity of Cu and U was highly pH-dependent. Copper concentrations required to inhibit growth (cell division) rate by 50% (72-h EC(50)) increased from 1.5 to 35 µg l(-1) as the pH decreased from 6.5 to 5.7. Similarly, the 72-h EC(50) values for U increased from 44 to 78 µg l(-1) over the same pH range. Calculation of Cu and U speciation using the geochemical model HARPHRQ, showed that differences in the concentrations of the free metal ions (Cu(2+) and UO(2)(2+)) were only minimal (<10%) between pH 5.7 and 6.5. The decreased toxicity at pH 5.7 was due to lower concentrations of cell-bound and intracellular Cu and U compared to those at pH 6.5. These results are explained in terms of the possible mechanism of competition between H(+) and the metal ion at the cell surface.

Journal Article↗
PubMed2001

Mining the chemical quarry with joint chemical probes: an application of latent semantic structure indexing (LaSSI) and TOPOSIM (Dice) to chemical database mining.

In this study we use a novel similarity search technique called latent semantic structure indexing (LaSSI) with joint chemical probes as queries to mine the MDL drug data report database. LaSSI is based on latent semantic indexing developed for searching textual databases. We use atom pair and topological torsion descriptors in our calculations. The results obtained with LaSSI are compared with another in-house similarity search technique TOPOSIM. The results from the similarity searches using joint chemical probes are significantly better than searches using single chemical probes for both LaSSI and TOPOSIM. The selected molecules are closely related in activity to their queries and are ranked among the top 300 scoring molecules of the 82 860 entries in the database. Our implementation of LaSSI is very fast and efficient in finding active compounds. The results also show that LaSSI consistently retrieves more diverse chemical structures representative of the joint chemical probes in comparison to TOPOSIM. The use of multimolecule topological probes to identify compounds complements the use of searching databases with 3D pharmacophore hypotheses.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Expression profiling using cDNA microarrays.

cDNA microarrays are capable of profiling gene expression patterns of tens of thousands of genes in a single experiment. DNA targets, in the form of 3' expressed sequence tags (ESTs), are arrayed onto glass slides (or membranes) and probed with fluorescent- or radioactively-labelled cDNAs. Here, we review technical aspects of cDNA microarrays, including the general principles, fabrication of the arrays, target labelling, image analysis and data extraction, management and mining.

Animals↗