Joshua Patrick Gray

United States Coast Guard Academy · Department of Chemical and Envrionmental Sciences

The risk of a terrorist attack in the United States has created challenges on how to effectively treat toxicities that result from exposure to chemical weapons. To address this concern, the United States has organized a trans‐agency initiative across academia, government, and industry to identify drugs to treat tissue injury resulting from exposure...

Objectives Military training centers and seagoing vessels are often environments at high risk for the spread of COVID-19 and other contagious diseases, because military trainees and personnel arrive after traveling from many parts of the country and live in congregate settings. We examined whether levels of SARS-CoV-2 genetic material in wastewater...

In higher education, student retention challenges and advancing student diversity are not new. Such institutional student retention challenges and student diversity promotions continue to require more focus and effort. A means to help address student retention and improve student diversity through faculty engagement in classrooms is inclusive pedag...

Hypersensitivity reactions occur when the immune system acts in an exaggerated manner leading to tissue damage. Delayed hypersensitivity (also known as a Type-IV hypersensitivity reaction) is an immunologic reaction that is mediated primarily by T cells and monocytes and presents hours to days after the antigen crosses into the skin. The most commo...

Metal antagonists are drugs associated with significant side effects; with limited options, medical practitioners must be vigilant in strategically adjusting dosage, desensitizing patients, and at times halting treatment altogether. Gastrointestinal chelating agents, the polystyrene sulphonates, are associated with gastrointestinal perforations fro...

The risk of a terrorist attack in the U.S. has created challenges on how to effectively treat toxicities that result from exposure to chemical weapons. To address this concern, the U.S. has organized a trans-agency initiative across academia, government, and industry to identify drugs to treat tissue injury resulting from exposure to chemical threa...

Military training centers may be high risk environments for the spread of disease such as COVID-19. Individuals arrive after traveling from many parts of the country, live in communal settings, and undergo high-interaction training. A pilot study of wastewater testing was initiated in February, 2021 to determine its feasibility as a sentinel survei...

Metal antagonists are drugs associated with significant side effects; with limited options, medical practioners must be vigilant in strategically adjusting dosage, desensitizing patients, and at times halting treatment altogether. Gastrointestinal chelating agents, the polystyrene sulphonates, are associated with gastrointestinal perforations from...

The Strategic National Stockpile (SNS) serves as a repository of materiel, including medical countermeasures (MCMs), that would be used to support the national health security response to a chemical, biological, radiological, or nuclear (CBRN) incident, either natural or terrorism-related. To support and advance the SNS, the National Institutes of...

This chapter describes the dermal toxicity events of the alkylating agent, sulfur mustard [bis (2-chloroethyl) sulfide], which ultimately causes detachment of the epidermis from the dermis. Skin exposure to sulfur mustard (SM) starts a series of dermal toxicity events with severity determined in part by mediators of injury that regulate inflammatio...

The side effects of drugs annual forms a series of volumes in which the adverse effects of drugs and adverse reactions to them are surveyed. The series supplements the contents of Meyler's Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions. This review of the January 2019–December 2019 publications on m...

The Society of Toxicology announces the development of a Learning Framework (https://www.toxicology.org/education/docs/SOT-Toxicology-Learning-Objectives.pdf) for undergraduate toxicology that will facilitate the development and sharing of evidence-based teaching materials for undergraduate toxicology educators throughout the world. This Learning F...

Electrochemistry is primarily taught in first-year undergraduate courses through batteries; this lab focuses instead on corrosion to apply electrochemical concepts of electrolytes, standard reduction potentials, galvanic cells, and other chemistry concepts including Le Chatelier’s Principle and Henry’s Law. Students investigate galvanic corrosion u...

The side effects of drugs annuals forms a series of volumes in which the adverse effects of drugs and adverse reactions to them are surveyed. The series supplements the contents of Meyler's Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions (ADRs) and Interactions. This review of the January 2017–December 2017 publicati...

The Side Effects of Drugs Annuals forms a series of volumes in which the adverse effects of drugs and adverse reactions to them are surveyed. The series supplements the contents of Meyler's Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions. This review of the January 2016-December 2016 publications on...

The side effects of drugs annuals forms a series of volumes in which the adverse effects of drugs and adverse reactions to them are surveyed. The series supplements the contents of Meyler's Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions. This review of the January 2015–December 2015 publications on...

NQO1 (NAD(P)H-quinone oxidoreductase 1) reduces quinones and xenobiotics to less-reactive compounds via 2-electron reduction, one feature responsible for the role of NQO1 in antioxidant defense in several tissues. In contrast, NADPH cytochrome P450 oxidoreductase (CYP450OR), catalyzes the 1-electron reduction of quinones and xenobiotics, resulting...

Exposure to chemotherapeutic agents has been linked to an increased risk of type 2 diabetes (T2D), a disease characterized by both the peripheral insulin resistance and impaired glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells. Using the rat β-cell line INS-1 832/13 and isolated mouse pancreatic islets, we investigated the effect...

Thymoquinone (2-Isopropyl-5-methylbenzo-1,4-quinone) is a major bioactive component of Nigella sativa, a plant used in traditional medicine to treat variety of symptoms, including elevated blood glucose levels in type 2 diabetic patients. Normalization of elevated blood glucose depends on both glucose disposal by peripheral tissues, and glucose-sti...

The side effects of drugs annuals forms a series of volumes in which the adverse effects of drugs and adverse reactions to them are surveyed. The series supplements the contents of Meyler's Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions. This review of the July 2013-December 2014 publications on met...

Type I Diabetes is characterized by the presence of hyperglycemia due to insulin deficiency and consequent impaired hepatic glucose metabolism. During diabetes, the liver becomes the most important tissue for the regulation of serum glucose. However, elevated glucose causes continuous oxidative damage to the liver, reducing its capacity to ameliora...

This chapter describes the dermal toxicity events of the alkylating agent, sulfur mustard [bis(2-chloroethyl) sulfide], which ultimately causes detachment of the epidermis from the dermis. Skin exposure to sulfur mustard (SM) starts a series of dermal toxicity events with severity determined in part by mediators of injury that regulate inflammation...

Anticholinergics are extensively used in medicine, such as, prior to anesthesia, as a prophylactic for preventing motion sickness, in symptomatic control of Parkinson's disease, in abnormal slowing of the heart in poisoning with organophosphates and other cholinergic drugs, and in the treatment of peptic ulcer and irritable bowel syndrome. Typicall...

In the lung, chemical redox cycling generates highly toxic reactive oxygen species that can cause alveolar inflammation and damage to the epithelium, as well as fibrosis. In this study, we identified a cytosolic NADPH-dependent redox cycling activity in mouse lung epithelial cells as sepiapterin reductase (SPR), an enzyme important for the biosynth...

The Agents of Bioterrorism course (BSBD 640, University of Maryland University College) is a graduate level course created in response to an elevated need for scientists working in the field of medical countermeasures in the years following 9/11. Students read and evaluate assigned current primary literature articles investigating medical counterme...

NADPH is an important component of the antioxidant defense system and a proposed mediator in glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells. An increase in the NADPH/NADP(+) ratio has been reported to occur within minutes following the rise in glucose concentration in β-cells. However, 30 min following the increase in glucose,...

Pancreatic β-cells release insulin in response to elevation of glucose from basal (4-7mM) to stimulatory (8-16mM) levels. Metabolism of glucose by the β-cell results in the production of low levels of reactive oxygen intermediates (ROI), such as hydrogen peroxide (H(2)O(2)), a newly recognized coupling factor linking glucose metabolism to insulin s...

Plasma membrane electron transport (PMET), a cytosolic/plasma membrane analog of mitochondrial electron transport, is a ubiquitous system of cytosolic and plasma membrane oxidoreductases that oxidizes cytosolic NADH and NADPH and passes electrons to extracellular targets. While PMET has been shown to play an important role in a variety of cell type...

Diquat and paraquat are nonspecific defoliants that induce toxicity in many organs including the lung, liver, kidney, and brain. This toxicity is thought to be due to the generation of reactive oxygen species (ROS). An important pathway leading to ROS production by these compounds is redox cycling. In this study, diquat and paraquat redox cycling w...

Inhalation of vesicants including sulfur mustard can cause significant damage to the upper airways. This is the result of vesicant-induced modifications of proteins important in maintaining the integrity of the lung. Cytochrome P450s are the major enzymes in the lung mediating detoxification of sulfur mustard and its metabolites. NADPH cytochrome P...

Mitomycin c (MMC), a quinone-containing anticancer drug, is known to redox cycle and generate reactive oxygen species. A key enzyme mediating MMC redox cycling is cytochrome P450 reductase, a microsomal NADPH-dependent flavoenzyme. In the present studies, Chinese hamster ovary (CHO) cells overexpressing this enzyme (CHO-OR cells) and corresponding...

Caveolin-1 (Cav-1) is a membrane scaffolding protein, which functions to regulate intracellular compartmentalization of various signaling molecules. In the present studies, transgenic mice with a targeted disruption of the Cav-1 gene (Cav-1(-/-)) were used to assess the role of Cav-1 in acetaminophen-induced hepatotoxicity. Treatment of wild-type m...

Insulin secretion from pancreatic beta cells is a process dependent on metabolism. While oxidative stress is a well-known inducer of beta cell toxicity and impairs insulin secretion, recent studies suggest that low levels of metabolically-derived reactive oxygen intermediates (ROI) also play a positive role in insulin secretion. Glucose metabolism...

Hospitalized infants are exposed to numerous devices containing the plasticizer di-(2-ethylhexyl) phthalate. Urinary levels of the phthalate metabolite, mono-(2-ethylhexyl) phthalate (MEHP), are markedly elevated in premature infants. Phthalates inactivate peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a nuclear transcription factor...

Thioredoxin reductase (TrxR) is a selenocysteine-containing flavoprotein that catalyzes the NADPH-dependent reduction of oxidized thioredoxin and plays a key role in regulating cellular redox homeostasis. In the present studies, we examined the effects of 2-chloroethyl ethyl sulfide (CEES), a model sulfur mustard vesicant, on TrxR in lung epithelia...

The formation of reactive oxygen species by the cytochrome P450 monooxygenase system is thought to be due to autoxidation of NADPH-cytochrome P450 reductase and the nonproductive decay of oxygen-bound cytochrome P450 intermediates. To characterize this process in recombinant microsomal enzymes, we used a highly sensitive hydrogen peroxide assay bas...

This chapter deals with the cutaneous actions of sulfur mustard (SM) and discusses the basic mechanism of action and mediators involved. While stable in lipophilic solvents, SM has a half life of only 24 min at room temperature in aqueous physiological solutions, since it rapidly reacts with water to form thiodiglycol and HCl. This rapid activation...

Sulfur mustard (SM), a chemical weapon first employed during WorldWar I, targets the skin, eyes, and lung. It remains a significant military and civilian threat. The characteristic response of human skin to SM involves erythema of delayed onset, followed by edema with inflammatory cell infiltration, the appearance of large blisters in the affected...

Background: glucagon like peptide-1 (GLP-1) and its analogue exendin-4 (Ex-4) enhance glucose stimulated insulin secretion (GSIS) and activate various signaling pathways in pancreatic beta-cells, in particular cAMP, Ca(2+) and protein kinase-B (PKB/Akt). In many cells these signals activate intermediary metabolism. However, it is not clear whether...

Pyruvate cycling has been implicated in glucose-stimulated insulin secretion (GSIS) from pancreatic beta-cells. The operation of some pyruvate cycling pathways is proposed to necessitate malate export from the mitochondria and NADP(+)-dependent decarboxylation of malate to pyruvate by cytosolic malic enzyme (ME1). Evidence in favor of and against a...

Background Glucagon like peptide-1 (GLP-1) and its analogue exendin-4 (Ex-4) enhance glucose stimulated insulin secretion (GSIS) and activate various signaling pathways in pancreatic β-cells, in particular cAMP, Ca2+ and protein kinase-B (PKB/Akt). In many cells these signals activate intermediary metabolism. However, it is not clear whether the ac...

Paraquat (1,1'-dimethyl-4,4'-bipyridinium) is a widely used herbicide known to induce skin toxicity. This is thought to be due to oxidative stress resulting from the generation of cytotoxic reactive oxygen intermediates (ROI) during paraquat redox cycling. The skin contains a diverse array of antioxidant enzymes which protect against oxidative stre...

Prostaglandins belong to a class of cyclic lipid-derived mediators synthesized from arachidonic acid via COX-1, COX-2 and various prostaglandin synthases. Members of this family include prostaglandins such as PGE(2), PGF(2alpha), PGD(2) and PGI(2) (prostacyclin) as well as thromboxane. In the present studies we analyzed the effects of UVB on prosta...

The one-electron reduction of redox-active chemotherapeutic agents generates highly toxic radical anions and reactive oxygen intermediates (ROI). A major enzyme catalyzing this process is cytochrome P450 reductase. Because many tumor cells highly express this enzyme, redox cycling of chemotherapeutic agents in these cells may confer selective antit...

Ultraviolet (UV) B causes oxidative stress, which has been implicated in carcinogenesis. We determined if the sensitivity of keratinocytes to UVB-induced oxidative stress is dependent on their differentiation state. In primary cultures of undifferentiated and differentiated mouse keratinocytes, UVB (25 mJ/cm(2)) stimulated production of reactive ox...

N-Benzyladriamycin-14-valerate (AD 198) is one of several novel anthracycline protein kinase C (PKC)-activating agents developed in our laboratories that demonstrates cytotoxic superiority over doxorubicin (Adriamycin; DOX) through its circumvention of multiple mechanisms of drug resistance. This characteristic is attributed at least partly to the...

N-Benzyladriamycin-14-valerate (AD 198) is one of several novel anthracycline protein kinase C (PKC)-activating agents developed in our laboratories that demonstrates cytotoxic superiority over doxorubicin (Adriamycin; DOX) through its circumvention of multiple mechanisms of drug resistance. This characteristic is attributed at least partly to the...

Pulmonary fibrosis is one of the most severe consequences of exposure to paraquat, an herbicide that causes rapid alveolar inflammation and epithelial cell damage. Paraquat is known to induce toxicity in cells by stimulating oxygen utilization via redox cycling and the generation of reactive oxygen intermediates. However, the enzymatic activity med...

Peroxisome proliferator-activated receptor alpha (PPARalpha) is a member of the nuclear receptor superfamily whose ligands, the peroxisome proliferators (PPs), are liver tumor promoters in rodents. Interaction cloning was performed using bacterially expressed PPARalpha to identify proteins involved in PP signaling. The ribosomal protein L11 (rpL11)...

Peroxisome proliferator-activated receptor alpha (PPARalpha) is a nuclear receptor activated by fatty acids, hypolipidemic drugs, and peroxisome proliferators (PPs). Like other nuclear receptors, PPARalpha is a phosphoprotein whose activity is affected by a variety of growth factor signaling cascades. In this study, the effects of protein kinase C...

Chemicals known as peroxisome proliferators (PPs) are the subject of intense study because of their ability to cause hepatocellular carcinoma in laboratory rodents. These chemicals act through a family of proteins termed the peroxisome proliferator-activated receptors (PPARs), in particular PPARalpha. It has become increasingly apparent that the ro...

The purpose of the present studies was to use a biomarker approach to examine xenobiotic exposure of brown bullhead in Presque Isle Bay, Lake Erie (USA). In particular, the presence of compounds that act through the aryl hydrocarbon receptor (AhR) was of interest due to its central role in gene regulation and carcinogenesis of dioxins and certain p...

The histerid beetle Carcinops pumilio (Erichson) occurs naturally in poultry house manure and is an important predator of house fly eggs and larvae. Because efforts to commercially produce C. pumilio have been unsuccessful, one fly control strategy under consideration is the direct transport of adult C. pumilio between poultry houses to facilitate...

Thesis (Ph.D.)--Pennsylvania State University, 2004. Microfilm (positive).