6 results on '"Cohen, Mitchell D."'
Search Results
2. A novel system to generate WTC dust particles for inhalation exposures
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Vaughan, Joshua M, Garrett, Brittany J, Prophete, Colette, Horton, Lori, Sisco, Maureen, Soukup, Joleen M, Zelikoff, Judith T, Ghio, Andrew, Peltier, Richard E, Asgharian, Bahman, Chen, Lung-Chi, and Cohen, Mitchell D
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- 2014
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3. Impact on rats from acute intratracheal inhalation exposures to WTC dusts.
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Cohen, Mitchell D., Prophete, Colette, Horton, Lori, Sisco, Maureen, Park, Sung-Hyun, Lee, Hyun-Wook, Zelikoff, Judith, and Chen, Lung-Chi
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DUST , *LEUCOCYTES , *RATS , *MONOCYTES , *GALECTINS - Abstract
Background: Studies have revealed the increased incidence of health disorders in First Responders (FR) who were at Ground Zero over the initial 72 hr after the World Trade Center (WTC) collapses. Previous studies in rats exposed to WTC dusts using exposure scenarios that mimicked FR mouthbreathing showed exposure led to altered expression of genes whose products could be involved in lung ailments. Nevertheless, it was uncertain if repeated exposures (as occurred in earliest days post-disaster) might have given rise to long-term changes in the lungs/other organs, in white blood cell (WBC) profiles, and/or systemic expression of select (mostly immune-related) proteins. Methods: To examine this, rats were exposed on 2 consecutive days (2 hr/d, intratracheal inhalation) to WTC dusts and then examined over a 1-yr period thereafter. At select times post-exposure, organ (lung, heart, liver, kidney, spleen) weights, WBC profiles, and blood levels of a variety of proteins were evaluated. Results: The study showed that over the 1-yr period, there were nominal effects on organ weights (absolute, index) as a result of the dust exposures. There were significant changes (relative to in naïve rats) in WBC profiles, with exposed rats having increased monocyte-macrophage and decreased lymphocyte percentages. The study also found that dust exposure led to significant systemic increases in many proteins, including MCP-1, RANTES, MMP-9, RAGE, and Galectin-3. Conclusions: These results provide further support for our longstanding hypothesis that the WTC dusts could potentially have acted as direct inducers of many of the health effects that have been seen in the exposed FR. [ABSTRACT FROM AUTHOR]
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- 2020
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4. Health effects of World Trade Center (WTC) Dust: An unprecedented disaster with inadequate risk management.
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Lippmann, Morton, Cohen, Mitchell D., and Chen, Lung-Chi
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PHYSIOLOGICAL effects of dust , *RESPIRATORY diseases , *GASTROESOPHAGEAL reflux , *COMPUTED tomography - Abstract
The World Trade Center (WTC) twin towers in New York City collapsed on 9/11/2001, converting much of the buildings' huge masses into dense dust clouds of particles that settled on the streets and within buildings throughout Lower Manhattan. About 80-90% of the settled WTC Dust, ranging in particle size from ∼2.5 μm upward, was a highly alkaline mixture of crushed concrete, gypsum, and synthetic vitreous fibers (SVFs) that was readily resuspendable by physical disturbance and low-velocity air currents. High concentrations of coarse and supercoarse WTC Dust were inhaled and deposited in the conductive airways in the head and lungs, and subsequently swallowed, causing both physical and chemical irritation to the respiratory and gastroesophageal epithelia. There were both acute and chronic adverse health effects in rescue/recovery workers; cleanup workers; residents; and office workers, especially in those lacking effective personal respiratory protective equipment. The numerous health effects in these people were not those associated with the monitored PM2.5 toxicants, which were present at low concentrations, that is, asbestos fibers, transition and heavy metals, polyaromatic hydrocarbons or PAHs, and dioxins. Attention was never directed at the very high concentrations of the larger-sized and highly alkaline WTC Dust particles that, in retrospect, contained the more likely causal toxicants. Unfortunately, the initial focus of the air quality monitoring and guidance on exposure prevention programs on low-concentration components was never revised. Public agencies need to be better prepared to provide reliable guidance to the public on more appropriate means of exposure assessment, risk assessment, and preventive measures. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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5. Impact of acute exposure to WTC dust on ciliated and goblet cells in lungs of rats.
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Cohen, Mitchell D., Vaughan, Joshua M., Garrett, Brittany, Prophete, Colette, Horton, Lori, Sisco, Maureen, Ghio, Andrew, Zelikoff, Judith, and Lung-chi, Chen
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DUST , *EXFOLIATIVE cytology , *LUNG cancer , *FIRE fighters , *ASTHMA , *ATHEROSCLEROSIS - Abstract
Clinical studies and the World Trade Center (WTC) Health Registry have revealed increases in the incidence of chronic (non-cancer) lung disorders among first responders (FR) who were at Ground Zero during the initial 72 h after the collapse. Our previous analyses of rats exposed to building-derived WTC dusts using exposure scenarios/levels that mimicked FR mouth-breathing showed that a single WTC dust exposure led to changes in expression of genes whose products could be involved in the lung ailments, but few other significant pathologies. We concluded that rather than acting as direct inducers of many of the FR health effects, it was more likely inhaled WTC dusts instead may have impacted on toxicities induced by other rescue-related co-pollutants present in Ground Zero air. To allow for such effects to occur, we hypothesized that the alkaline WTC dusts induced damage to the normal ability of the lungs to clear inhaled particles. To validate this, rats were exposed on two consecutive days (2 h/d, by intratracheal inhalation) to WTC dust (collected 12–13 September 2001) and examined over a 1-yr period thereafter for changes in the presence of ciliated cells in the airways and hyperplastic goblet cells in the lungs. WTC dust levels in the lungs were assessed in parallel to verify that any changes in levels of these cells corresponded with decreases in host ability to clear the particles themselves. Image analyses of the rat lungs revealed a significant decrease in ciliated cells and increase in hyperplastic goblet cells due to the single series of WTC dust exposures. The study also showed there was only a nominal non-significant decrease (6–11%) in WTC dust burden over a 1-yr period after the final exposure. These results provide support for our current hypothesis that exposure to WTC dusts caused changes in airway morphology/cell composition; such changes could, in turn, have led to potential alterations in the clearance/toxicities of other pollutants inhaled at Ground Zero in the critical initial 72-h period. [ABSTRACT FROM PUBLISHER]
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- 2015
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6. Acute high-level exposure to WTC particles alters expression of genes associated with oxidative stress and immune function in the lung.
- Author
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Cohen, Mitchell D., Vaughan, Joshua M., Garrett, Brittany, Prophete, Colette, Horton, Lori, Sisco, Maureen, Kodavanti, Urmila P., Ward, William O., Peltier, Richard E., Zelikoff, Judith, and Chen, Lung-chi
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SEPTEMBER 11 Terrorist Attacks, 2001 , *RESPIRATORY organ injuries , *OXIDATIVE stress , *IMMUNE response , *LUNG immunology , *FIRST responders , *RNA , *HEALTH - Abstract
First responders (FR) present at Ground Zero in the first 72 h after the World Trade Center (WTC) collapsed have progressively exhibited significant respiratory injuries. The few toxicology studies performed to date evaluated effects from just fine (< 2.5 µm) WTC dusts; none examined health effects/toxicities from atmospheres bearing larger particle sizes, despite the fact the majority (> 96%) of dusts were > 10 µm and most FR likely entrained dusts by mouth breathing. Using a system that generated/delivered supercoarse (10-53 µm) WTC dusts to F344 rats (in a manner that mimicked FR exposures), this study sought to examine potential toxicities in the lungs. In this exploratory study, rats were exposed for 2 h to 100 mg WTC dust/m3 (while under isoflurane [ISO] anesthesia) or an air/ISO mixture; this dose conservatively modeled likely exposures by mouth-breathing FR facing ≈750-1000 mg WTC dust/m3. Lungs were harvested 2 h post-exposure and total RNA extracted for subsequent global gene expression analysis. Among the > 1000 genes affected by WTC dust (under ISO) or ISO alone, 166 were unique to the dust exposure. In many instances, genes maximally-induced by the WTC dust exposure (relative to in naïve rats) were unchanged/inhibited by ISO only; similarly, several genes maximally inhibited in WTC dust rats were largely induced/unchanged in rats that received ISO only. These outcomes reflect likely contrasting effects of ISO and the WTC dust on lung gene expression. Overall, the data show that lungs of rats exposed to WTC dust (under ISO) - after accounting for any impact from ISO alone - displayed increased expression of genes related to lung inflammation, oxidative stress, and cell cycle control, while several involved in anti-oxidant function were inhibited. These changes suggested acute inflammogenic effects and oxidative stress in the lungs of WTC dust-exposed rats. This study, thus, concludes that a single very high exposure to WTC dusts could potentially have adversely affected the respiratory system - in terms of early inflammatory and oxidative stress processes. As these changes were not compared with other types of dusts, the uniqueness of these WTC-mediated effects remains to be confirmed. It also still remains to be determined if these effects might have any relevance to chronic lung pathologies that became evident among FR who encountered the highest dust levels on September 11, 2001 and the 2 days thereafter. Ongoing studies using longer-range post-exposure analyses (up to 1-year or more) will help to determine if effects seen here on genes were acute, reversible, or persistent, and associated with corresponding histopathologic/biochemical changes in situ. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
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