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Many heavy metals, including nickel, cadmium, and chromium are toxic industrial chemicals with an exposure. While these substances are known to produce adverse health effects leading to health problems, the detailed mechanisms remain unclear. To elucidate the processes involved in the toxicity of these metals at the molecular level and to perform a comparative analysis, H4-II-E-C3 rat liver-derived cell lines were treated with each metal and gene expression patterns were determined. We identified both common and unique biological responses to exposure to the metals. All three metals induced oxidative stress. Although all three metals are known to be genotoxic, evidence for DNA damage in our study only exists in response to chromium. Nickel induced a hypoxic response as well as inducing genes involved in chromatin structure. Cadmium distinctly perturbed genes related to endoplasmic reticulum stress and invoked the unfolded protein response leading to apoptosis. With these studies, we have completed the first gene expression comparative analysis of nickel, cadmium, and chromium in H4-II-E-C3 cells., The original document contains color images.

Respiratory symptoms are frequently reported in personnel deployed to the Middle East. This project characterized the respiratory toxicity of inhaled Iraqi sand (IS). Adult rats underwent a 6-wk inhalation to air or mainstream cigarette smoke (MSCS) (3h/d, 5d/wk) that included exposure to IS or crystalline silica (1 mg/m3, 19h/d, 7d/wk) or air during the last w weeks. Assessments included motor activity, whole-body plethysmography, cytological and biochemical analysis of bronchoalveolar lavage fluid, lung metal burden, nasal and lung pathology and changes in lung protein and gene expression. A number of metals including nickel, manganese, and vanadium concentrations wee seen in IS-exposed rats, suggesting that several metals present in IS are bioavailable. Rats exposed to IS only developed mild inflammation in the anterior nose and lung. Silica inhalation was associated with some pulmonary responses that were not seen in IS-exposed rats, such as mild laryngeal and tracheal inflammation, mild tracheal epithelial hyperplasia, and elevated lung silica concentrations. MSCS inhalation with or without co-exposure to MSCS and silica has more widespread airway lesions when compared with rats exposed to MSCS only. Silica-exposed rats had more robust pulmonary gene expression and proteomic responses than that seen in IS-exposed rat. Our studies show that the respiratory toxicity of IS is qualitatively similar to or less than that seen following short-term silica exposure.

This thesis document was issued under the authority of another institution, not NPS. At the time it was written, a copy was added to the NPS Library collection for reasons not now known. It has been included in the digital archive for its historical value to NPS. Not believed to be a CIVINS (Civilian Institutions) title., The object of this investigation was to determine to performance characteristics of two axially coincident crifices in series., http://archive.org/details/aninvestigationo109456455, Lieutenant, United States Navy, Lieutenant (j.g.), United States Coast Guard

We exposed Xenopus tropicalis to 1, 3.3, 11 and 36 ug/L octylphenol from Neiuwkoop-Faber (NF) state 46 tadpoles through adulthood in a flow-through water system. At NF stage 5, a random subsample of froglets was collected and assessed, while the remaining frogs were exposed through 31 weeks. Significant induction of vitellogenin was observed in the high treatment at the larval subsampling for both sexes, but not at the final sampling for either sex. No significant deviation from control for sex ratio was observed for either sampling period, suggesting minimal to no effect on gonad differentiation. Oviduct development was observed in males exposed to octylphenol. These results indicate that octylphenol exposure can induce vitellogenin in immature froglets and the development of oviducts in male adult frogs. The lack of effect observed on the developing gonads suggests that in amphibians, secondary sex characteristics are more susceptible to estrogenic compounds than developing gonads.

Despite the wealth of sequence data and new technologies that can scan large portions of the transcriptome of proteome in a single experiment, attempts to identify human biomarkers of toxicity have met with limited success. We have adapted an in vitro model system to identify proteins secreted by a human hepatoma-derived cell line (HepG2/C3A) in response to toxicant exposure. Using quantitative proteomics, we can find alterations in the abundance of proteins at the source of damage--liver cells--that are likely to be present in blood samples of exposed animals. In a proof of concept experiment, conditioned medium from cells exposed to ethanol was subjected to quantitative mass spectral analysis after abundant proteins were immunodepleted. Eighty seven proteins were identified with almost half changing in abundance. Some of these were only identified in the highest treatment condition and presumably result from the release of intracellular proteins into the medium when the cell membrane is disrupted upon cell death. However, the majority of the identified proteins reflect known consequences of ethanol exposure or alcoholism., Pub. in Journal of Proteome Research, v9, p5794 5802, 2010.

Small arms-range (SAR) soils can be contaminated with metals from spent copper (Cu)-jacketed bullets. Avian species are particularly at risk because they are exposed to lead (Pb) through ingestion of grit, soil intake from preening, or ingestion of contaminated food near ranges. Examination of the effects of Pb on birds at ranges have mainly focused on intake and toxicity of Pb shot pellets or fragments; however, Pb in soils may be an important pathway of exposure. To evaluate the uptake and effects of Pb from an actual range, the soil fraction (250 mum) from a contaminated SAR soil was used to dose pigeons (Columbia livia) for 14 days at low (200 mug Pb and 215 mug Cu/d) and high (5400 mug Pb and 430 mug Cu/d)., Published in Archives of Environmental Contamination and Toxicology, v60 n2 p351-360, 2010. The original document contains color images.

The wide use of organophosphorus (OP) pesticides makes them an important public health concern. Persistent effects of exposure and the mechanism of neuronal degeneration are continuing issues in OP toxicology. To elucidate early steps in the mechanisms of OP toxicity, we studied alterations in global gene and protein expression in Caenorhabditis elegans exposed to OPs using microarrays and mass spectrometry. We tested two structurally distinct OPs (dichlorvos and fenamiphos) and employed a mechanistically different third neurotoxicant, mefloquine, as an outgroup for analysis. Treatment levels used concentrations of chemical sufficient to prevent the development of 10%, 50% or 90% of mid-vulval L4 larvae into early gravid adults (EGA) at 24 h after exposure in a defined, bacteria-free medium., Published in BMC Genomics, v10 n202 p1-21, 2009.

Inhalation of diesel exhaust particles (DEP) is characterized by lung injury and inflammation with significant increases in the numbers of polymorphonuclear leukocytes and alveolar macrophages. This influx of cellular infiltrates is associated with the activation of multiple genes, including cytokines and chemokines, and the production of reactive oxygen species. The pathogenesis of the lung injury is not fully understood, but alterations in the presence or abundance of a number of proteins in the lung have been observed. The present study investigates global alterations in the proteome of bronchoalveolar lavage fluid taken from rats 1, 7 or 30 days after exposure to 5, 35, or 50 mg/kg of animal weight of DEP. Analysis by surface-enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF) identified two distinct peaks that appeared as an acute response post-exposure at all doses in all animals. These two peaks, with mass to charge ratios (m/z) of 9,000 and 10,100 were identified as anaphylatoxin C3a and calgranulin A by additional mass spectral investigation using liquid chromatography coupled to mass spectrometry (LC/MS)., Prepared in collaboration with Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV. Published in Environmental Health Perspectives, v115 n5 p756-763, May 2007.

In 1996, the U.S. Congress mandated the development of a screening program for endocrine-disrupting chemicals (EDCs) using validated test systems. Subsequently, the Endocrine Disruptor Screening and Testing Advisory Committee recommended the development of a standardized amphibian assay for tier 2 testing of EDCs. For that reason, a tier 2 testing protocol using Xenopus (Silurana) tropicalis and a 30-week, flow-through exposure to the antiandrogen flutamide from stage 46 tadpoles through sexually mature adult frogs were developed and evaluated in this pilot study. The endpoints for this study included measurements of frog body lengths and weights, liver weights, ovary/egg mass weights, testicular and ovarian histopathology, plasma vitellogenin levels, and notes on any abnormalities observed at necropsy. Increasing exposure concentrations to flutamide caused significant increases in frogs with no recognizable gonadal tissue and increased body and liver weights in male frogs, whereas the body lengths and weights decreased significantly in female frogs. Important issues must be resolved before a tier 2 amphibian assay can be further developed and validated, including the establishment of baseline values in the controls for the parameters under study; the maintenance, measurement, and timing of exposure concentrations; and the development of additional biomolecular markers of effect. This study demonstrated the feasibility of conducting long-term EDC exposure studies using X. tropicalis., Prepared in collaboration with the U.S. Food and Drug Administration, Beltsville, MD; Science Applications International Corp., Fort Detrick, MD; and with the the Dept. of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI. Published in Environmental Toxicology and Chemistry, v26, n3, p555-564, 2007.

A liquid chromatographic method has been developed for the analysis of N-Nitroso-N- ethylurea (ENU) in salt water by high performance liquid chromatography (HPLC). Samples are injected directly onto a HPLC without sample preparation. Separation of ENU from possible interferences found in salt water was achieved using a C-18 DB column and a mobile phase containing methanol and water. A programmable ultra- violet detector was used to monitor the effluent for ENU. The stability of ENU in the sample matrix is examined at various concentrations and various pH values.

A liquid chromatographic method has been developed for the analysis of 5-Br deoxyuridine (BrdU) in well water. The samples are injected directly onto a high performance liquid chromatograph (HPLC) without further sample preparation. Separation of BrdU from possible interferences found in well water was achieved by using a C-18 column and a mobile phase containing water and methanol. A programmable ultraviolet (UV) detector was used to monitor the effluent for BrdU. HPLC provides a rapid and reproducible method for the analysis of BrdU. High Performance Liquid Chromatograph (HPLC), 5-Bromo- 2'deoxyuridine (BrdU), Ultraviolet (UV).

Liquid chromatographic method has been developed for the determination of 1,4-diamino-2,3-dihydroanthraquinone (DDA), 2-(21-quinolinyl)- 1,3-indandione (QID), 1-methylamino-anthraquinone (MAA), and 1,4-di-p- toluidinoanthraquinone (DTA). A relatively rapid and reliable HPLC method has been developed for the determination of selected colored smokes on glass fiber filter discs. The sample preparation process was streamlined by extracting the colored-smokes/disc samples into acetonitrile followed by filtration and direct injection into a high performance liquid chromatograph equipped with a programmable ultraviolet (UV) spectrophotometric detector. A mixed-mode C18/ cation column provided adequate resolution and optimal peak symmetry for all four of the colored smokes investigated. The precision and accuracy data and detection limits are included in the report.

Black and white photograph (dated ca. 1904) of penman W. E. Dennis, who worked with W. A. Baird. Appended at right is a signature from the back of the photograph. Dennis was honored in Tier 1 of the Penman's Hall of Fame.

Certificate of Membership (dated ca. 1904) in the Penman's Art Journal Self-Help Club. Members of the Club were asked to pay a fee of 50 cents for a certificate.

Ornamental flourish (dated 1912) by penman W. E. Dennis.

Cover artwork for the February 1898 issue of The Penman's Art Journal

Ornamental flourish (dated 1898) by artist W. E. Dennis.

Cover artwork (dated ca. 1897) for The Penman's Art Journal.

Ornamental flourish (dated 1912) by penman W. E. Dennis, set around an anonymous rhyme, 'Kind hearts are gardens.'

Title artwork (dated ca. 1909) for the Penman's Art Journal, executed by penman W. E. Davis.

Cover artwork (dated ca. 1900) for The Penman's Art Journal, by artist W. E. Dennis of Brooklyn, N.Y.

The object of this investigation was to determine to performance characteristics of two axially coincident crifices in series.