@article{heniff_chen_christiansen_harms_law_legner_linder_2022, title={Cutaneous epitheliotropic lymphosarcoma in a captive white catfish (Ameiurus catus Linnaeus)}, volume={4}, ISSN={["1365-2761"]}, url={https://doi.org/10.1111/jfd.13625}, DOI={10.1111/jfd.13625}, abstractNote={Abstract}, journal={JOURNAL OF FISH DISEASES}, author={Heniff, Ashlyn C. and Chen, Laura R. and Christiansen, Emily F. and Harms, Craig A. and Law, Jerry M. and Legner, Christian and Linder, Keith E.}, year={2022}, month={Apr} }
 @article{wolf_law_lynch_2021, title={Non-cardiogenic pulmonary oedema and multisystemic haemorrhage secondary to an accidental intravenous injection of melarsomine in a dog}, volume={9}, ISSN={["2052-6121"]}, DOI={10.1002/vrc2.196}, abstractNote={Abstract}, journal={VETERINARY RECORD CASE REPORTS}, author={Wolf, Johanna and Law, Jerry M. and Lynch, Alex}, year={2021}, month={Sep} }
 @article{krasner_hancock-ronemus_christian_griffith_lewbart_law_2019, title={Histological evaluation of five suture materials in the telson ligament of the American horseshoe crab (Limulus polyphemus)}, volume={7}, ISSN={["2167-8359"]}, DOI={10.7717/peerj.7061}, abstractNote={An ideal suture material supports healing, minimizes inflammation, and decreases the likelihood of secondary infection. While there are published recommendations for suture materials in some invertebrates, there are no published recommendations forLimulus polyphemusor any chelicerate. This study evaluates the histological reaction of horseshoe crabs to five commonly used suture materials: monofilament nylon, silk, poliglecaprone, polydioxanone, and polyglycolic acid. None of the materials were superior with regards to holding nor was there any dehiscence. Nylon evoked the least amount of tissue reaction. This work also provides a histopathological description of the soft membrane at the hinge area between the opisthosoma and telson (telson ligament) and comments on euthanasia with intracardiac eugenol.}, journal={PEERJ}, author={Krasner, Ami E. and Hancock-Ronemus, Amy and Christian, Larry S. and Griffith, Emily H. and Lewbart, Gregory A. and Law, Jerry M.}, year={2019}, month={Aug} }
 @article{phillips_paez-rosas_flowers_cullen_law_colitz_deresienski_lohmann_lewbart_2018, title={EVALUATION OF THE OPHTHALMIC DISEASE AND HISTOPATHOLOGIC EFFECTS DUE TO THE OCULAR TREMATODE PHILOPHTHALMUS ZALOPHI ON JUVENILE GALAPAGOS SEA LIONS (ZALOPHUS WOLLEBAEKI)}, volume={49}, ISSN={["1937-2825"]}, DOI={10.1638/2017-0096.1}, abstractNote={Abstract The Galapagos sea lion (Zalophus wollebaeki) is an otariid species endemic to the Galapagos archipelago and is currently listed as endangered. The ocular trematode Philophthalmus zalophi was recently reported to affect the survival of juvenile Galapagos sea lions on Santa Cruz Island, resulting in marked ophthalmic changes. This study evaluated the ophthalmic disease and histopathologic effects of P. zalophi on juvenile Galapagos sea lions in the largest rookery located on San Cristóbal Island. Twenty juvenile Galapagos sea lions (10 male and 10 female) were evaluated among five sites in the rookery El Malecón. Ophthalmic examination, including fluorescein staining and evaluation of the adnexa, cornea, and sclera, were performed on each eye. The presence, number, and location of ocular parasites were determined, and parasites were collected for identification. Conjunctival biopsy was performed on 11 animals: 2 that lacked parasites and gross lesions and 9 with both parasites and gross lesions. All parasites collected were confirmed as P. zalophi and identified in 80% (16/20) of the study animals and 70% (28/40) of the examined eyes. Philophthalmus zalophi was most frequently found attached to the nictitating membrane but also located on the palpebral conjunctiva or cornea. The most common clinical signs were varying degrees of conjunctival hyperemia (28/40 eyes), most frequently of the nictitating membrane and mucoid ocular discharge (12/40 eyes). The number of parasites was significantly associated with the degree of conjunctival hyperemia (P < 0.001). Histopathology of conjunctival biopsies revealed organized lymphoid follicles and lymphoplasmacytic infiltrates. The histopathologic changes and gross lesions were likely due to the parasite's attachment to the conjunctiva. This study provides additional details of P. zalophi infection in juvenile Galapagos sea lions. Further research is warranted to detail the life cycle of this parasite, transmission to sea lions, and potential treatment protocols.}, number={3}, journal={JOURNAL OF ZOO AND WILDLIFE MEDICINE}, author={Phillips, Brianne E. and Paez-Rosas, Diego and Flowers, James R. and Cullen, John M. and Law, Jerry M. and Colitz, Carmen and Deresienski, Diane and Lohmann, Kenneth J. and Lewbart, Gregory A.}, year={2018}, month={Sep}, pages={581–590} }
 @article{friedenberg_brown_meurs_law_2018, title={Lymphocyte Subsets in the Adrenal Glands of Dogs With Primary Hypoadrenocorticism}, volume={55}, ISSN={["1544-2217"]}, DOI={10.1177/0300985816684914}, abstractNote={ Primary hypoadrenocorticism, or Addison’s disease, is an autoimmune condition common in certain dog breeds that leads to the destruction of the adrenal cortex and a clinical syndrome involving anorexia, gastrointestinal upset, and electrolyte imbalances. Previous studies have demonstrated that this destruction is strongly associated with lymphocytic-plasmacytic inflammation and that the lymphocytes are primarily T cells. In this study, we used both immunohistochemistry and in situ hybridization to characterize the T-cell subtypes involved. We collected postmortem specimens of 5 dogs with primary hypoadrenocorticism and 2 control dogs and, using the aforementioned techniques, showed that the lymphocytes are primarily CD4+ rather than CD8+. These findings have important implications for improving our understanding of the pathogenesis and in searching for the underlying causative genetic polymorphisms. }, number={1}, journal={VETERINARY PATHOLOGY}, author={Friedenberg, S. G. and Brown, D. L. and Meurs, K. M. and Law, J. McHugh}, year={2018}, month={Jan}, pages={177–181} }
 @article{grieshaber_penland_kwak_cope_heise_law_shea_aday_rice_kullman_et al._2018, title={Relation of contaminants to fish intersex in riverine sport fishes}, volume={643}, ISSN={0048-9697}, url={http://dx.doi.org/10.1016/J.SCITOTENV.2018.06.071}, DOI={10.1016/J.SCITOTENV.2018.06.071}, abstractNote={Endocrine active compounds (EACs) are pollutants that have been recognized as an emerging and widespread threat to aquatic ecosystems globally. Intersex, the presence of female germ cells within a predominantly male gonad, is considered a biomarker of endocrine disruption caused by EACs. We measured a suite of EACs and assessed their associated impacts on fish intersex occurrence and severity in a large, regulated river system in North Carolina and South Carolina, USA. Our specific objective was to determine the relationship of contaminants in water, sediment, and fish tissue with the occurrence and severity of the intersex condition in wild, adult black bass (Micropterus), sunfish (Lepomis), and catfish (Ictaluridae) species at 11 sites located on the Yadkin-Pee Dee River. Polycyclic aromatic hydrocarbons (PAHs), ethinylestradiol (EE2), and heavy metals were the most prevalent contaminants that exceeded effect levels for the protection of aquatic organisms. Fish intersex condition was most frequently observed and most severe in black basses and was less frequently detected and less severe in sunfishes and catfishes. The occurrence of the intersex condition in fish showed site-related effects, rather than increasing longitudinal trends from upstream to downstream. Mean black bass and catfish tissue contaminant concentrations were higher than that of sunfish, likely because of the latter's lower trophic position in the food web. Principal component analysis identified waterborne PAHs as the most correlated environmental contaminant with intersex occurrence and severity in black bass and sunfish. As indicated by the intersex condition, EACs have adverse but often variable effects on the health of wild sport fishes in this river, likely due to fluctuations in EAC inputs and the dynamic nature of the riverine system. These findings enhance the understanding of the relationship between contaminants and fish health and provide information to guide ecologically comprehensive conservation and management decisions.}, journal={Science of The Total Environment}, publisher={Elsevier BV}, author={Grieshaber, C.A. and Penland, T.N. and Kwak, T.J. and Cope, W.G. and Heise, R.J. and Law, J.M. and Shea, Damian and Aday, D.D. and Rice, J.A. and Kullman, S.W. and et al.}, year={2018}, month={Dec}, pages={73–89} }
 @article{tokarz_heffelfinger_jima_gerlach_shah_rodriguez-nunez_kortum_fletcher_nordone_law_et al._2017, title={Disruption of Trim9 function abrogates macrophage motility in vivo}, volume={102}, ISSN={0741-5400 1938-3673}, url={http://dx.doi.org/10.1189/jlb.1A0816-371R}, DOI={10.1189/jlb.1a0816-371r}, abstractNote={Abstract}, number={6}, journal={Journal of Leukocyte Biology}, publisher={Wiley}, author={Tokarz, Debra A. and Heffelfinger, Amy K. and Jima, Dereje D. and Gerlach, Jamie and Shah, Radhika N. and Rodriguez-Nunez, Ivan and Kortum, Amanda N. and Fletcher, Ashley A. and Nordone, Shila K. and Law, J. McHugh and et al.}, year={2017}, month={Oct}, pages={1371–1380} }
 @article{lee pow_tilahun_creech_law_cope_kwak_rice_aday_kullman_2017, title={Windows of Susceptibility and Consequences of Early Life Exposures to 17β–estradiol on Medaka (Oryzias latipes) Reproductive Success}, volume={51}, ISSN={0013-936X 1520-5851}, url={http://dx.doi.org/10.1021/ACS.EST.7B01568}, DOI={10.1021/ACS.EST.7B01568}, abstractNote={Estrogens and estrogen mimics are commonly found in surface waters and are associated with deleterious effects in fish populations. Impaired fertility and fecundity in fish following chronic exposures to estrogens and estrogen mimics during critical windows in development are well documented. However, information regarding differential reproductive effects of exposure within defined developmental stages remains sparse. In this study, reproductive capacity was assessed in Japanese medaka (Oryzias latipes) after exposure to two concentrations of 17β-estradiol (E2β; 2 ng/L and 50 ng/L) during four distinct stages of development: gonad development, gonad differentiation, development of secondary sex characteristics (SSC) and gametogenesis. Exposure to E2β did not adversely impact survival, hatch success, growth, or genotypic ratios. In contrast, exposure to 50 ng/L E2β during SSC development altered phenotypic ratios and SSC. Exposure to both E2β treatments reduced reproductive capacity (fertility, fecundity) by 7.3-57.4% in adult medaka breeding pairs, with hindrance of SSC development resulting in the largest disruption in breeding capacity (51.6-57.4% decrease) in the high concentration. This study documents differential effects among four critical stages of development and provides insight into factors (window of exposure, exposure concentration and duration of exposure period) contributing to reproductive disruption in fish.}, number={9}, journal={Environmental Science & Technology}, publisher={American Chemical Society (ACS)}, author={Lee Pow, Crystal S.D. and Tilahun, Kedamawit and Creech, Kari and Law, J. Mac and Cope, W. Gregory and Kwak, Thomas J. and Rice, James A. and Aday, D. Derek and Kullman, Seth W.}, year={2017}, month={Apr}, pages={5296–5305} }
 @article{lee pow_law_kwak_cope_rice_kullman_aday_2016, title={Endocrine active contaminants in aquatic systems and intersex in common sport fishes}, volume={36}, ISSN={0730-7268}, url={http://dx.doi.org/10.1002/ETC.3607}, DOI={10.1002/ETC.3607}, abstractNote={Abstract}, number={4}, journal={Environmental Toxicology and Chemistry}, publisher={Wiley}, author={Lee Pow, Crystal S.D. and Law, J. Mac and Kwak, Thomas J. and Cope, W. Gregory and Rice, James A. and Kullman, Seth W. and Aday, D. Derek}, year={2016}, month={Oct}, pages={959–968} }
 @article{hurley-sanders_harms_christiansen_clarke_law_2015, title={Exuberant granulation tissue response associated with Neobenedenia sp. (Monogenea: Capsalidae) infestation in two cobia, Rachycentron canadum (Linnaeus)}, volume={39}, ISSN={0140-7775}, url={http://dx.doi.org/10.1111/jfd.12360}, DOI={10.1111/jfd.12360}, abstractNote={Abstract}, number={3}, journal={Journal of Fish Diseases}, publisher={Wiley}, author={Hurley-Sanders, J and Harms, C and Christiansen, E and Clarke, E, III and Law, J}, year={2015}, month={Apr}, pages={277–283} }
 @article{hurley-sanders_levine_nelson_law_showers_stoskopf_2015, title={Key metabolites in tissue extracts ofElliptio complanataidentified using1H nuclear magnetic resonance spectroscopy}, volume={3}, ISSN={2051-1434}, url={http://dx.doi.org/10.1093/conphys/cov023}, DOI={10.1093/conphys/cov023}, abstractNote={We used 1H-NMR to describe the freshwater mussel metabolome. Muscle, digestive gland, mantle and gill tissues yielded profiles with possible biomarkers of physiologic function. These preliminary studies provide evidence for potential use of digestive gland and mantle tissue for studying physiological impacts of location, sex and reproductive condition on Elliptio complanata.}, number={1}, journal={Conservation Physiology}, publisher={Oxford University Press (OUP)}, author={Hurley-Sanders, Jennifer L. and Levine, Jay F. and Nelson, Stacy A. C. and Law, J. M. and Showers, William J. and Stoskopf, Michael K.}, year={2015}, pages={cov023} }
 @article{shivappa_christian_noga_law_lewbart_2015, title={Laboratory Evaluation of Safety and Efficacy for Melafix (Melaleuca cajuputi Extract)}, volume={24}, ISSN={1557-5063}, url={http://dx.doi.org/10.1053/J.JEPM.2015.04.020}, DOI={10.1053/J.JEPM.2015.04.020}, abstractNote={Abstract A study was performed at the North Carolina State University, College of Veterinary Medicine, to assess the safety and efficacy of Melafix, an aquarium product produced by Mars Fishcare Incorporated. Studies were carried out on the goldfish ( Carassius auratus ), a freshwater species, and the false percula clownfish ( Amphiprion ocellaris ), a marine fish. Animals were monitored closely and evaluated microscopically after exposure to Melafix according to the label directions for a period of 28 days. Water-quality parameters were monitored on a daily basis. The use of Melafix on goldfish and clownfish appears to be safe as no adverse effects were noted during the experimental period. The results also showed that Melafix has no effect on the water-quality parameters tested. In vitro efficacy studies were conducted by determining the minimum inhibitory concentration and minimum bactericidal concentration of Melafix on various pathogens. The study revealed that Melafix had no significant bactericidal or inhibitory effect on any of the pathogens tested. This observation suggests that anecdotal benefits of Melafix are not owing to antibacterial activity. This topic requires further research and possibly an in vivo study.}, number={2}, journal={Journal of Exotic Pet Medicine}, publisher={Elsevier BV}, author={Shivappa, Raghunath B. and Christian, Larry S. and Noga, Edward J. and Law, Jerry M. and Lewbart, Gregory A.}, year={2015}, month={Apr}, pages={188–192} }
 @article{wolf_baumgartner_blazer_camus_engelhardt_fournie_frasca_groman_kent_khoo_et al._2015, title={Nonlesions, misdiagnoses, missed diagnoses, and other interpretive challenges in fish histopathology studies: A guide for investigators, authors, reviewers, and readers}, volume={43}, number={3}, journal={Toxicologic Pathology}, author={Wolf, J. C. and Baumgartner, W. A. and Blazer, V. S. and Camus, A. C. and Engelhardt, J. A. and Fournie, J. W. and Frasca, S. and Groman, D. B. and Kent, M. L. and Khoo, L. H. and et al.}, year={2015}, pages={297–325} }
 @article{sackett_pow_rubino_aday_cope_kullman_rice_kwak_law_2015, title={Sources of endocrine-disrupting compounds in North Carolina waterways: A geographic information systems approach}, volume={34}, ISSN={0730-7268}, url={http://dx.doi.org/10.1002/ETC.2797}, DOI={10.1002/ETC.2797}, abstractNote={Abstract}, number={2}, journal={Environmental Toxicology and Chemistry}, publisher={Wiley}, author={Sackett, Dana K. and Pow, Crystal Lee and Rubino, Matthew J. and Aday, D. Derek and Cope, W. Gregory and Kullman, Seth and Rice, James A. and Kwak, Thomas J. and Law, Mac}, year={2015}, month={Jan}, pages={437–445} }
 @article{wolf_baumgartner_blazer_camus_engelhardt_fournie_frasca_groman_kent_khoo_et al._2014, title={Nonlesions, Misdiagnoses, Missed Diagnoses, and Other Interpretive Challenges in Fish Histopathology Studies}, volume={43}, ISSN={0192-6233 1533-1601}, url={http://dx.doi.org/10.1177/0192623314540229}, DOI={10.1177/0192623314540229}, abstractNote={ Differentiating salient histopathologic changes from normal anatomic features or tissue artifacts can be decidedly challenging, especially for the novice fish pathologist. As a consequence, findings of questionable accuracy may be reported inadvertently, and the potential negative impacts of publishing inaccurate histopathologic interpretations are not always fully appreciated. The objectives of this article are to illustrate a number of specific morphologic findings in commonly examined fish tissues (e.g., gills, liver, kidney, and gonads) that are frequently either misdiagnosed or underdiagnosed, and to address related issues involving the interpretation of histopathologic data. To enhance the utility of this article as a guide, photomicrographs of normal and abnormal specimens are presented. General recommendations for generating and publishing results from histopathology studies are additionally provided. It is hoped that the furnished information will be a useful resource for manuscript generation, by helping authors, reviewers, and readers to critically assess fish histopathologic data. }, number={3}, journal={Toxicologic Pathology}, publisher={SAGE Publications}, author={Wolf, Jeffrey C. and Baumgartner, Wes A. and Blazer, Vicki S. and Camus, Alvin C. and Engelhardt, Jeffery A. and Fournie, John W. and Frasca, Salvatore, Jr and Groman, David B. and Kent, Michael L. and Khoo, Lester H. and et al.}, year={2014}, month={Aug}, pages={297–325} }
 @article{gonzalez_fogle_baker_hughes_law_motsinger-reif_blikslager_2014, title={Operative factors associated with short-term outcome in horses with large colon volvulus: 47 cases from 2006 to 2013}, volume={47}, ISSN={0425-1644}, url={http://dx.doi.org/10.1111/evj.12273}, DOI={10.1111/evj.12273}, abstractNote={Summary}, number={3}, journal={Equine Veterinary Journal}, publisher={Wiley}, author={Gonzalez, L. M. and Fogle, C. A. and Baker, W. T. and Hughes, F. E. and Law, J. M. and Motsinger-Reif, A. A. and Blikslager, A. T.}, year={2014}, month={May}, pages={279–284} }
 @article{hill_lascelles_m. law_blikslager_2014, title={The Effect of Tramadol and Indomethacin Coadministration on Gastric Barrier Function in Dogs}, volume={28}, ISSN={0891-6640}, url={http://dx.doi.org/10.1111/jvim.12345}, DOI={10.1111/jvim.12345}, abstractNote={BackgroundTramadol is a centrally acting analgesic that is often used in conjunction with nonsteroidal anti‐inflammatory drugs (NSAIDs). The effect of coadministration of tramadol and indomethacin on gastric barrier function in dogs is unknown.}, number={3}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Hill, T.L. and Lascelles, B.D.X. and M. Law, J. and Blikslager, A.T.}, year={2014}, month={Mar}, pages={793–798} }
 @article{taylor_foster_law_centeno_fornero_henderson_trager_stockelman_dorman_2013, title={Assessment of geographical variation in the respiratory toxicity of desert dust particles}, volume={25}, ISSN={["0895-8378"]}, DOI={10.3109/08958378.2013.797524}, abstractNote={Abstract The health consequences of sand particle inhalation are incompletely understood. This project evaluated the respiratory toxicity of sand particles collected at military bases near Fort Irwin USA, in Iraq (Camp Victory, Taji and Talil), and Khost Afghanistan. Our primary focus was on assessing the role of soluble metals in the respiratory toxicity of the sand particles using in vitro and in vivo methods. Replicating rat type II alveolar cell cultures (RLE-6TN) were exposed to sand extracts or vehicle control in serum-free media for ≤24 h. Cytotoxicity was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and assessment of lactate dehydrogenase leakage. The relative in vitro cytotoxicity of the sand extracts was Taji ≈ Talil > Afghanistan > Camp Victory ≈ Fort Irwin. We also assessed extracts of Camp Victory, Afghanistan, and Taji sand for acute and delayed pulmonary toxicity in rats following intratracheal administration. Assessments included biochemical analysis of bronchoalveolar lavage fluid (BALF) and lung histopathology. The in vitro cytotoxicity assay results were partially predictive of in vivo responses. The more cytotoxic Taji sand extract induced an acute irritant response in rats following intratracheal administration. Rats given the less cytotoxic Camp Victory sand extract had minimal biochemical or cytological BALF changes whereas rats given either the Afghanistan or Taji sand extracts demonstrated BALF changes that were suggestive of mild lung inflammation. Unexpectedly, we observed similar lung pathology in all extract-exposed rats. The results of our study can be used to prioritize future particle inhalation studies or guide epidemiological study design.}, number={7}, journal={INHALATION TOXICOLOGY}, author={Taylor, Karen and Foster, Melanie L. and Law, J. McHugh and Centeno, Jose A. and Fornero, Elisa and Henderson, M. Stephen and Trager, Sabrina A. and Stockelman, Michael G. and Dorman, David C.}, year={2013}, month={Jun}, pages={405–416} }
 @article{schmidt_jokinen_law_pandiri_weddle_wolf_sills_2013, title={Environmental Pathobiology and Global Opportunities}, volume={50}, ISSN={["1544-2217"]}, DOI={10.1177/0300985813485098}, abstractNote={The mission of the American College of Veterinary Pathologists (ACVP) is to foster excellence in veterinary pathology for the protection and improvement of animal, human, and environmental health as a benefit to society. One mechanism by which the College promotes the advancement and sharing of knowledge to the scientific community is through our journal Veterinary Pathology. In keeping with our College’s mission to become the premier forum for presenting leading-edge pathobiological research, our editor-in-chief, Carl Alden, has decided to broaden the focus of this publication by creating sections modeled along the Journal’s specialty groups. The establishment of a section on Environmental Pathobiology will provide opportunities for diagnosticians, pathologists, pathology residents, and scientists to learn and publish about current mechanistic research and various types of diagnostic methods used to assess and clarify disease processes caused by exposure to environmental contaminants. The significance of environmental contaminants as agents of disease and public health concern, as well as their costly impact on health care and industry, is well established. Some past and current high-profile examples of these agents and their associated diseases include asbestos and mesothelioma, gasoline additives and lead encephalopathy, DDT and negative impact in birds and other wildlife, and, most recently, the potential impact of large crude oil spills on the flora and fauna of coastal environments. Today, the challenge is no less; a multiplicity of various indoor and outdoor environmental factors, including nanoparticles, dusts, organic and inorganic chemicals, metals, alternative and herbal medicines, pharmaceuticals, food additives, pesticides, biological agents, and radiation, including electromagnetic fields, have the capacity to directly or indirectly cause toxic injury or influence the animal or human host’s response to infectious disease. Animal models help us to understand cellular and molecular mechanisms that influence the pathogenesis of diseases associated with exposure to environmental agents. Veterinary pathologists, by virtue of their training in comparative medicine and pathobiology, play a pivotal role by identifying and clarifying mechanisms of toxicity and carcinogenicity in animal models. A broad-based knowledge of comparative anatomy, morphologic responses to tissue and cellular injury, toxicological principles, and molecular biology allows pathologists to propose and test accurate hypotheses regarding toxic mechanisms, the results of which may aid in hazard identification and risk assessment. Furthermore, a pathologist’s diagnostic and interpretive skills can provide the first predictive clues that certain environmental agents may be harmful to animals or humans. Anatomic and clinical pathologists are engaged in diverse activities that include the diagnosis of disease conditions in companion and food/fiber animals, teaching and hypothesis testing research in academic institutions, and the assessment of toxicologic bioassays in laboratory animals for commercial and governmental sponsors. In addition, many pathologists are either currently leading teams or collaborating with researchers in the evaluation and study of environmental agents of concern to human health in animal models. The section on Environmental Pathobiology will provide (1) an opportunity for sharing featured national/international scholarly articles on toxicity study outcomes of environmental factors in animals and (2) a venue for pathology/testing strategies and environmental monitoring discussions that concern global environmental issues. Included will be outcomes of investigative and regulatory-based studies that use genetically engineered animal models laboratory animals. The section on Environmental Pathobiology will also offer a high-profile refereed outlet for publishing environmentally relevant findings in alternative animal species, including domestic and exotic animals; lower vertebrates such as fish, amphibians, and birds; various forms of wildlife; and nonhuman primates. The Environmental Pathobiology section is anticipated to serve as a forum for global collaboration among pathologists and other scientists. One sign of the desire for such collaborative effort is the recent formation of the Environmental Toxicologic Pathology Special Interest Group (ETPSIG) of the Society of}, number={5}, journal={VETERINARY PATHOLOGY}, author={Schmidt, S. P. and Jokinen, M. P. and Law, J. M. and Pandiri, A. R. and Weddle, D. L. and Wolf, J. C. and Sills, R. C.}, year={2013}, month={Sep}, pages={733–734} }
 @misc{meuten_law_stromberg_cullen_2013, title={From Bipeds to an Honorary Member of the American College of Veterinary Pathologists}, volume={50}, ISSN={["1544-2217"]}, DOI={10.1177/0300985813480219}, abstractNote={For a moment, we thought Dr de Lahunta would remain complimentary of our article that questioned the use of the words autopsy vs necropsy. His point is well made—if we are going to suggest nomenclature preferences, we should be accurate with our use of nomenclature. The crus or leg is, as he states, there are no 4-legged animals. We hope we have it correct this time. It has been 42 years since Dr ‘‘d’’ said to one of us (D.J.M.) in a barn at Cornell, ‘‘Hello, my name is Sandy de Lahunta; come look at this goat and let’s see if we can figure out where his neurologic deficit is.’’ Don had no idea he was about to be grilled by a legend, and the legend is still grilling. Dr Russ Cattley also reminded us of an important reference: Autopsy of the Horse, by James Rooney. Russ is absolutely correct we should have cited this excellent book and/or just followed Dr Rooney’s lead from 40 years ago. Fortunately, Dr Rooney agreed with the preference of the word autopsy and apparently felt the distinction from necropsy quite pedantic. We are enjoying the exchanges we have stimulated, and if we are correct and using the term autopsy results in more animals being autopsied, then can we support the recommendation? The autopsy remains the quality control standard for human and veterinary hospitals, yet the percentage of cases being submitted for an autopsy appears to be on the decline. Medicine, pathology, and all our specialties are dependent on follow-up data to assess diseases, diagnoses, and treatments, medical and surgical. For oncology, there is no more certain way to assess disease-free intervals, recurrence, and metastases than an autopsy. Extracting data from clinical assessment, palpation of excision lines, palpation of regional lymph nodes, and imaging body cavities are good, but they are not as definitive as the results of an autopsy. However, the number of studies that use an autopsy and histopathology to report accurate clinical outcome data is minuscule. It is essential to conclude these expensive and lengthy studies with an autopsy and histopathology. If the word autopsy is more acceptable to pet owners than necropsy, then we hope all clinicians will use this term, written and verbally, as they explain how further examination of their pet is essential to help other pets and researchers. No one better knows the value of correlating clinical signs with postmortem lesions than Dr de Lahunta. He made a distinguished career and raised neuropathology to new standards by integrating neurology and pathology (via autopsies). Thank you.}, number={3}, journal={VETERINARY PATHOLOGY}, author={Meuten, D. J. and Law, J. M. and Stromberg, P. C. and Cullen, J. M.}, year={2013}, month={May}, pages={365–365} }
 @article{wettere_kullmam_hinton_law_2013, title={Immunohistochemical characterization of the hepatic progenitor cell compartment in medaka (oryzias latipes) following hepatic injury}, volume={149}, DOI={10.1016/j.jcpa.2013.03.008}, abstractNote={Laboratory fish species are used increasingly in biomedical research and are considered robust models for the study of regenerative processes. Studies investigating the response of the fish liver to injury have demonstrated the presence of a ductular reaction and oval-like cells in injured and regenerating liver. To date, however, it is unclear if this cell population is the piscine equivalent of oval cells (OCs) or intermediate hepatobiliary cells (IHBCs) identified in rodents and man, respectively. The present study defines the process of OC differentiation in fish liver using histopathology, immunohistochemistry and transmission electron microscopy. To generate OC proliferation in Japanese medaka (Oryzias latipes), hepatic injury was induced by exposure of adult fish to either microcystin LR or dimethylnitrosamine. A transgenic strain of medaka expressing a red fluorescent protein (RFP) exclusively in hepatocytes was used. The morphological response to injury was characterized by a ductular reaction comprised of cytokeratin (CK) AE1/AE3(+) OCs progressing to IHBCs variably positive for CK and RFP and finally mature RFP(+) hepatocytes and CK(+) cholangiocytes. These observations support a bipotential differentiation pathway of fish OCs towards hepatocytes and cholangiocytes. Ultrastructural morphology confirmed the presence of OCs and differentiation towards hepatocytes. These results demonstrated clear similarities between patterns of reaction to injury in fish and mammalian livers. They also confirm the presence of, and support the putative bipotential lineage capabilities of, the fish OC.}, number={4}, journal={Journal of Comparative Pathology}, author={Wettere, A. J. Van and Kullmam, Seth and Hinton, D. E. and Law, J. M.}, year={2013}, pages={434–445} }
 @article{van wettere_law_hinton_kullman_2013, title={Phenotypic Characterization of Transgenic Japanese Medaka (Oryzias latipes) That Express a Red Fluorescent Protein in Hepatocytes}, volume={42}, ISSN={0192-6233 1533-1601}, url={http://dx.doi.org/10.1177/0192623313499643}, DOI={10.1177/0192623313499643}, abstractNote={ Transgenic organisms that express fluorescent proteins are used frequently for in vivo visualization of proteins and cells. The phenotype of a transgenic medaka ( Oryzias latipes) strain that expresses a red fluorescent protein (RFP) in hepatocytes was characterized using light and fluorescence microscopy, immunohistochemistry, and transmission electron microscopy (TEM). Expression of RFP was first detected by confocal fluorescence microscopy in the location of the liver bud of live medaka embryos at 60 hr postfertilization (developmental stage 27). Subsequently, RFP signal was observed exclusively in hepatocytes throughout life using fluorescence microscopy in live fish and immunohistochemistry in formalin-fixed, paraffin-embedded liver sections. As the fish aged, prominent intracytoplasmic eosinophilic inclusions immunoreactive for RFP were observed by light microscopy and were correlated with membrane-bound electron dense inclusions on TEM. These results define the onset and location of RFP expression in the Tg(zf.L-fabp:DsRed) medaka and characterize a histologic phenotype that results from RFP expression in hepatocytes. }, number={3}, journal={Toxicologic Pathology}, publisher={SAGE Publications}, author={Van Wettere, Arnaud J. and Law, J. Mac and Hinton, David E. and Kullman, Seth W.}, year={2013}, month={Aug}, pages={616–621} }
 @article{jennings_wise_nickeleit_maes_cianciolo_piero_law_kim_mccalla_breuhaus_et al._2013, title={Polyomavirus-Associated Nephritis in 2 Horses}, volume={50}, ISSN={0300-9858 1544-2217}, url={http://dx.doi.org/10.1177/0300985813476063}, DOI={10.1177/0300985813476063}, abstractNote={ Polyomaviruses produce latent and asymptomatic infections in many species, but productive and lytic infections are rare. In immunocompromised humans, polyomaviruses can cause tubulointerstitial nephritis, demyelination, or meningoencephalitis in the central nervous system and interstitial pneumonia. This report describes 2 Standardbred horses with tubular necrosis and tubulointerstitial nephritis associated with productive equine polyomavirus infection that resembles BK polyomavirus nephropathy in immunocompromised humans. }, number={5}, journal={Veterinary Pathology}, publisher={SAGE Publications}, author={Jennings, S. H. and Wise, A. G. and Nickeleit, V. and Maes, R. K. and Cianciolo, R. E. and Piero, F. Del and Law, J. M. and Kim, Y. and McCalla, A. C. and Breuhaus, B. A. and et al.}, year={2013}, month={Feb}, pages={769–774} }
 @article{posner_scott_law_2013, title={Repeated exposure of goldfish (Carassius auratus) to tricaine methanesulfonate (MS-222)}, volume={44}, ISSN={1042-7260 1937-2825}, url={http://dx.doi.org/10.1638/2012-0151r1.1}, DOI={10.1638/2012-0151r1.1}, abstractNote={Abstract:  Goldfish that have been repeatedly exposed to tricaine methanesulfonate (MS-222) require greater concentration of the drug to attain equivalent planes of anesthesia, but the mechanism for this increased anesthetic need is unknown. Minimum anesthetic concentration (MAC) is a commonly used method with which to compare anesthetics. It was hypothesized that fish exposed to MS-222 daily would have an increased MAC. It was also hypothesized that fish exposed daily to MS-222 would develop histomorphologic changes to their gills to explain the increasing demand. Forty-nine Serasa comet goldfish were enrolled and were divided into three populations (n = 15, n = 15, and n = 19). In trial 1, using an up–down method, MAC was determined daily after 4 min of exposure to MS-222 for which the starting concentration was 160 mg/L. In trial 2, MAC was determined following 2 min of exposure to MS-222 for which the starting concentration was 260 mg/L. In trial 3, four naive fish were euthanatized and gills collected for histology and electron microscopy (EM). The remaining fish were exposed to MS-222 daily for 4 wk. Four fish were euthanatized and their gills submitted for similar examination at 2 wk and 4 wk. MAC for fish exposed to MS-222 for 4 min increased from 120 to 160 mg/L. The regression line had a slope of 1.51 ± 0.26 (R2 = 0.65; P < 0.0001). MAC for fish exposed to MS-222 for 2 min increased from 210 pmm to 220 mg/L; the regression line had a slope of 0.52 ± 0.38 (R2 = 0.12; P = 0.2). Histologic and EM examination of gills did not show morphologic changes indicative of a reaction to MS-222. Goldfish in this study had an increased requirement for MS-222 following daily exposure for 4 min but not following daily exposure for 2 min at a higher concentration. The cause of this increased anesthetic need is not related to morphologic changes to the gills.}, number={2}, journal={Journal of Zoo and Wildlife Medicine}, publisher={American Association of Zoo Veterinarians}, author={Posner, Lysa Pam and Scott, Gregory N. and Law, J. McHugh}, year={2013}, month={Jun}, pages={340–347} }
 @article{van wettere_law_hinton_kullman_2012, title={Anchoring hepatic gene expression with development of fibrosis and neoplasia in a toxicant-induced fish model of liver injury}, volume={41}, ISSN={["1533-1601"]}, url={http://tpx.}, DOI={10.1177/0192623312464308}, abstractNote={ Fish have been used as laboratory models to study hepatic development and carcinogenesis but not for pathogenesis of hepatic fibrosis. In this study, a dimethylnitrosamine-induced fish model of hepatic injury was developed in Japanese medaka ( Oryzias latipes) and gene expression was anchored with the development of hepatic fibrosis and neoplasia. Exposed livers exhibited mild hepatocellular degenerative changes 2 weeks’ postexposure. Within 6 weeks, hepatic fibrosis/cirrhosis was evident with development of neoplasia by 10 weeks. Stellate cell activation and development of fibrosis was associated with upregulation of transforming growth factor beta 1 ( tgfb1), tgfb receptor 2, mothers against decapentaplegic homolog 3 ( smad3a), smad3b, beta-catenin ( ctnnb1), myc, matrix metalloproteinase ( mmp2), mmp14a, mmp14b, tissue inhibitors of metalloproteinase ( timp) 2a, timp2b, timp3, collagen type I alpha 1a ( col1a1a), and col1a1b and a less pronounced increase in mmp13 and col4a1 expression. Tgfb receptor I expression was unchanged. Immunohistochemistry suggested that biliary epithelial cells and stellate cells were the main producers of TGF-β1. This study identified a group of candidate genes likely to be involved in the development of hepatic fibrosis and demonstrated that the TGF-β pathway likely plays a major role in the pathogenesis. These results support the medaka as a viable fish model of hepatic fibrosis. }, number={5}, journal={Toxicologic Pathology}, author={Van Wettere, A.J. and Law, J.M. and Hinton, D.E. and Kullman, S.W.}, year={2012}, pages={1–17} }
 @article{clarke_harms_law_flowers_williams_ring_mcginty_hopper_sullivan_2012, title={Clinical and Pathological Effects of the Polyopisthocotylean Monogenean, Gamacallum macroura in White Bass}, volume={24}, ISSN={["0899-7659"]}, DOI={10.1080/08997659.2012.713889}, abstractNote={Abstract}, number={4}, journal={JOURNAL OF AQUATIC ANIMAL HEALTH}, author={Clarke, Elsburgh O., III and Harms, Craig A. and Law, J. McHugh and Flowers, James R. and Williams, Valerie N. and Ring, Brad D. and McGinty, Andrew S. and Hopper, Michael and Sullivan, Craig V.}, year={2012}, month={Dec}, pages={251–257} }
 @article{hobbie_deangelo_george_law_2012, title={Neoplastic and Nonneoplastic Liver Lesions Induced by Dimethylnitrosamine in Japanese Medaka Fish}, volume={49}, ISSN={["1544-2217"]}, DOI={10.1177/0300985811409443}, abstractNote={ Small fish models have been used for decades in carcinogenicity testing. Demonstration of common morphological changes associated with specific mechanisms is a clear avenue by which data can be compared across divergent phyletic levels. Dimethylnitrosamine, used in rats to model human alcoholic cirrhosis and hepatic neoplasia, is also a potent hepatotoxin and carcinogen in fish. We recently reported some striking differences in the mutagenicity of DMN in lambda cII transgenic medaka fish vs. Big Blue® rats, but the pre-neoplastic and neoplastic commonalities between the two models are largely unknown. Here, we focus on these commonalities, with special emphasis on the TGF- β pathway and its corresponding role in DMN-induced hepatic neoplasia. Similar to mammals, hepatocellular necrosis, regeneration, and dysplasia; hepatic stellate cell and “spindle cell” proliferation; hepatocellular and biliary carcinomas; and TGF-β1 expression by dysplastic hepatocytes all occurred in DMN-exposed medaka. Positive TGF- β1 staining increased with increasing DMN exposure in bile preductular epithelial cells, intermediate cells, immature hepatocytes and fewer mature hepatocytes. Muscle specific actin identified hepatic stellate cells in DMN-exposed fish. Additional mechanistic comparisons between animal models at different phyletic levels will continue to facilitate the interspecies extrapolations that are so critical to toxicological risk assessments. }, number={2}, journal={VETERINARY PATHOLOGY}, author={Hobbie, K. R. and DeAngelo, A. B. and George, M. H. and Law, J. M.}, year={2012}, month={Mar}, pages={372–385} }
 @article{choi_cope_harms_law_2012, title={Rapid decreases in salinity, but not increases, lead to immune dysregulation in Nile tilapia,Oreochromis niloticus(L.)}, volume={36}, ISSN={0140-7775}, url={http://dx.doi.org/10.1111/j.1365-2761.2012.01417.x}, DOI={10.1111/j.1365-2761.2012.01417.x}, abstractNote={Abstract}, number={4}, journal={Journal of Fish Diseases}, publisher={Wiley}, author={Choi, K and Cope, W G and Harms, C A and Law, J M}, year={2012}, month={Nov}, pages={389–399} }
 @article{cope_holliman_kwak_oakley_lazaro_shea_augspurger_law_henne_ware_et al._2011, title={Assessing water quality suitability for shortnose sturgeon in the Roanoke River, North Carolina, USA with an in situ bioassay approach}, volume={27}, ISSN={["0175-8659"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-78751690460&partnerID=MN8TOARS}, DOI={10.1111/j.1439-0426.2010.01570.x}, abstractNote={Summary 
 
The aim of this study was to determine the suitability of water quality in the Roanoke River of North Carolina for supporting shortnose sturgeon Acipenser brevirostrum, an endangered species in the United States. Fathead minnows Pimephales promelas were also evaluated alongside the sturgeon as a comparative species to measure potential differences in fish survival, growth, contaminant accumulation, and histopathology in a 28-day in situ toxicity test. Captively propagated juvenile shortnose sturgeon (total length 49 ± 8 mm, mean ± SD) and fathead minnows (total length 39 ± 3 mm, mean ± SD) were used in the test and their outcomes were compared to simultaneous measurements of water quality (temperature, dissolved oxygen, pH, conductivity, total ammonia nitrogen, hardness, alkalinity, turbidity) and contaminant chemistry (metals, polycyclic aromatic hydrocarbons, organochlorine pesticides, current use pesticides, polychlorinated biphenyls) in river water and sediment. In the in situ test, there were three non-riverine control sites and eight riverine test sites with three replicate cages (25 × 15-cm (OD) clear plexiglass with 200-μm tear-resistant Nitex® screen over each end) of 20 shortnose sturgeon per cage at each site. There was a single cage of fathead minnows also deployed at each site alongside the sturgeon cages. Survival of caged shortnose sturgeon among the riverine sites averaged 9% (range 1.7–25%) on day 22 of the 28-day study, whereas sturgeon survival at the non-riverine control sites averaged 64% (range 33–98%). In contrast to sturgeon, only one riverine deployed fathead minnow died (average 99.4% survival) over the 28-day test period and none of the control fathead minnows died. Although chemical analyses revealed the presence of retene (7-isopropyl-1-methylphenanthrene), a pulp and paper mill derived compound with known dioxin-like toxicity to early life stages of fish, in significant quantities in the water (251–603 ng L−1) and sediment (up to 5000 ng g−1 dry weight) at several river sites, no correlation was detected of adverse water quality conditions or measured contaminant concentrations to the poor survival of sturgeon among riverine test sites. Histopathology analysis determined that the mortality of the river deployed shortnose sturgeon was likely due to liver and kidney lesions from an unknown agent(s). Given the poor survival of shortnose sturgeon (9%) and high survival of fathead minnows (99.4%) at the riverine test sites, our study indicates that conditions in the Roanoke River are incongruous with the needs of juvenile shortnose sturgeon and that fathead minnows, commonly used standard toxicity test organisms, do not adequately predict the sensitivity of shortnose sturgeon. Therefore, additional research is needed to help identify specific limiting factors and management actions for the enhancement and recovery of this imperiled fish species.}, number={1}, journal={JOURNAL OF APPLIED ICHTHYOLOGY}, author={Cope, W.G. and Holliman, F.M. and Kwak, T.J. and Oakley, N.C. and Lazaro, P.R. and Shea, Damian and Augspurger, T. and Law, J.M. and Henne, J.P. and Ware, K.M. and et al.}, year={2011}, month={Feb}, pages={1–12} }
 @article{boylan_harms_waltzek_law_garner_cassell_fatzinger_govett_2011, title={Clinical report: hyperplastic adipose lids in mackerel scad, Decapterus macarellus (Cuvier)}, volume={34}, ISSN={0140-7775}, url={http://dx.doi.org/10.1111/j.1365-2761.2011.01306.x}, DOI={10.1111/j.1365-2761.2011.01306.x}, abstractNote={1 South Carolina Aquarium, Charleston, SC, USA 2 North Carolina State University, Center for Marine Sciences and Technology, Morehead City, NC, USA 3 Department of Environmental and Global Health, College of Public Health and Health Professions, University of Florida, Gainesville, FL, USA 4 College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA 5 Northwest ZooPath, Monroe, WA, USA 6 North Carolina Aquarium at Fort Fisher, Kure Beach, NC, USA 7 Western University, College of Veterinary Medicine, Pomona, CA, USA}, number={12}, journal={Journal of Fish Diseases}, publisher={Wiley}, author={Boylan, S M and Harms, C A and Waltzek, T and Law, J M and Garner, M and Cassell, J and Fatzinger, M H and Govett, P}, year={2011}, month={Oct}, pages={921–925} }
 @article{law_stromberg_meuten_cullen_2011, title={Necropsy or Autopsy? It’s All About Communication!}, volume={49}, ISSN={0300-9858 1544-2217}, url={http://dx.doi.org/10.1177/0300985811410722}, DOI={10.1177/0300985811410722}, abstractNote={Several of us have decided that communication is more important than tradition. Yes, Virginia, we were all drilled in the discipline of veterinary pathology by traditionalists. We’re stubborn individualists, aren’t we? Greats like John King have necropsied thousands of animals, and we want our procedure to be distinguished from the ‘‘other’’ side—the RDs (well okay, the MDs). The short answer is that ‘‘necropsy’’ literally means ‘‘death examination’’ or examination of death and finds its application in the study of bodies following death. The term is general without reference to species. ‘‘Autopsy’’ literally means ‘‘self-examination,’’ and some of us were taught that the frame of reference for ‘‘self’’ referred to the postmortem examination of ‘‘ourselves’’ or our own species, humans. As such, postmortem examination of nonhumans was proscribed from using the term and was designated ‘‘necropsy.’’ But hold on there a minute, let’s see what Webster has to say. Or as Don Meuten likes to say, ‘‘Show me the reference!’’}, number={2}, journal={Veterinary Pathology}, publisher={SAGE Publications}, author={Law, M. and Stromberg, P. and Meuten, D. and Cullen, J.}, year={2011}, month={Jun}, pages={271–272} }
 @article{tobias_barnes_law_2011, title={Pathology in Practice}, volume={239}, ISSN={["0003-1488"]}, DOI={10.2460/javma.239.8.1065}, number={8}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Tobias, Jeremy R. and Barnes, H. John and Law, J. McHugh}, year={2011}, month={Oct}, pages={1065–1067} }
 @article{flowers_law_carvajal-endara_2011, title={Pseudosonsinotrema megalorchis n. sp. (Digenea: Pleurogenidae) from the Paramo Marsupial Frog, Gastrotheca pseustes (Anura: Hemiphractidae), Ecuador}, volume={78}, ISSN={["1525-2647"]}, DOI={10.1654/4460.1}, abstractNote={Abstract Approximately 400 specimens of a previously undescribed species of Pseudosonsinotrema sp. (Digenea: Pleurogenidae) were collected from a Paramo marsupial frog, Gastrotheca pseustes (Anura: Hemiphractidae), from the Museo de Zoología of the Pontificia Universidad Católica del Ecuador, Quito, Ecuador. The new digenean species, Pseudosonsinotrema megalorchis n. sp., can be distinguished from others in the genus primarily by its large testes. Flukes attached to the mucosa of the host's intestine cause ulcerative enteritis and become embedded in the intestinal wall, eliciting a severe granulomatous enteritis. This is the first report of this digenean genus from Ecuador and the first report of helminths from G. pseustes. Pseudosonsinotrema saudii is transferred to the genus Pleurogenoides as Pleurogenoides saudii (Ramadan, Banaja, and Saoud, 1980) n. comb. The intense host inflammatory reaction and the relatively low fecundity of specimens suggest that G. pseustes is not the natural host of P. megalorchis.}, number={1}, journal={COMPARATIVE PARASITOLOGY}, author={Flowers, James R. and Law, Mac and Carvajal-Endara, Sofia}, year={2011}, month={Jan}, pages={15–20} }
 @article{law_reuvekamp_glaum_lee_kang_whangbo_kremer_2011, title={Quasi-one-dimensional antiferromagnetism and multiferroicity in CuCrO4}, volume={84}, ISSN={["1098-0121"]}, DOI={10.1103/physrevb.84.014426}, abstractNote={The bulk magnetic properties of the new quasi-one-dimensional Heisenberg antiferromagnet, CuCrO${}_{4}$, were characterized by magnetic susceptibility, heat capacity, optical spectroscopy, electron paramagnetic resonance and dielectric capacitance measurements, and density functional evaluations of the intrachain and interchain spin-exchange interactions. We found type-II multiferroicity below the N\'eel temperature of 8.2(5) K, arising from competing antiferromagnetic nearest-neighbor (${J}_{\mathrm{nn}}$) and next-nearest-neighbor (${J}_{\mathrm{nnn}}$) intrachain spin-exchange interactions. Experimental and theoretical results indicate that the ratio ${J}_{\mathrm{nn}}$/${J}_{\mathrm{nnn}}$ is close to 2, putting CuCrO${}_{4}$ in the vicinity of the Majumdar-Ghosh point.}, number={1}, journal={PHYSICAL REVIEW B}, author={Law, J. M. and Reuvekamp, P. and Glaum, R. and Lee, C. and Kang, J. and Whangbo, M. -H. and Kremer, R. K.}, year={2011}, month={Jul} }
 @article{ott_mcdowell_turner_law_adler_yoder_jones_2011, place={Hoboken, N.J}, title={Two Myristoylated Alanine-Rich C-Kinase Substrate (MARCKS) Paralogs are Required for Normal Development in Zebrafish}, volume={294}, ISSN={1932-8486}, url={http://dx.doi.org/10.1002/ar.21453}, DOI={10.1002/ar.21453}, abstractNote={Abstract}, note={: 2007),}, number={9}, journal={The Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology}, publisher={Wiley}, author={Ott, Laura E. and Mcdowell, Zachary T. and Turner, Poem M. and Law, J. Mchugh and Adler, Kenneth B. and Yoder, Jeffrey A. and Jones, Samuel L.}, year={2011}, month={Aug}, pages={1511–1524} }
 @article{lentz_eversole_law_means_2010, title={Cellular Proliferation, Cell Death, and Liver Histology in Gambusia affinis After Dietary Exposure to Benzidine and 2-Aminofluorene}, volume={29}, ISSN={["1092-874X"]}, DOI={10.1177/1091581810363745}, abstractNote={ Chronic exposure to arylamines through diet and/or smoking has been associated with genetic changes and tumorigenesis. Cellular proliferation, apoptosis, and histological changes in liver tissue were investigated in Gambusia affinis ( G affinis) after chronic dietary exposure to 6.9 mM and 0.069 mM concentrations of benzidine (BZ), 2-aminofluorene (2AF), and their combination for 4, 8, and 12 weeks, respectively. The proliferation assay indicated non–dose-dependent increases in cellular proliferation over the controls for all treatment groups at 4 and 12 weeks but not at 8 weeks except for the low dose of 2AF. The apoptosis assay showed effects in the low-dose group of 2AF and BZ at 4 weeks only. Hematoxylin/eosin staining of liver tissue revealed an increase in oval/spindle cell proliferation and altered foci formation in the treated groups compared with controls. These results demonstrate a mammalian-like response to 2AF and BZ in G affinis liver. }, number={3}, journal={INTERNATIONAL JOURNAL OF TOXICOLOGY}, author={Lentz, Susan and Eversole, Rob and Law, J. McHugh and Means, Jay C.}, year={2010}, month={May}, pages={247–258} }
 @article{wooten_lascelles_cook_law_blikslager_2010, title={Evaluation of the relationship between lesions in the gastroduodenal region and cyclooxygenase expression in clinically normal dogs}, volume={71}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.71.6.630}, DOI={10.2460/ajvr.71.6.630}, abstractNote={Abstract}, number={6}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Wooten, Jenna G. and Lascelles, B. Duncan X. and Cook, Vanessa L. and Law, J. Mac and Blikslager, Anthony T.}, year={2010}, month={Jun}, pages={630–635} }
 @article{howarth_law_law_mondon_kullman_hinton_2010, title={Exposure to the synthetic FXR agonist GW4064 causes alterations in gene expression and sublethal hepatotoxicity in eleutheroembryo medaka (Oryzias latipes)}, volume={243}, ISSN={["1096-0333"]}, DOI={10.1016/j.taap.2009.11.022}, abstractNote={The small freshwater teleost, medaka (Oryzias latipes), has a history of usage in studies of chronic toxicity of liver and biliary system. Recent progress with this model has focused on defining the medaka hepatobiliary system. Here we investigate critical liver function and toxicity by examining the in vivo role and function of the farnesoid X receptor alpha (FXRα, NR1H4), a member of the nuclear receptor superfamily that plays an essential role in the regulation of bile acid homeostasis. Quantitative mRNA analysis of medaka FXRα demonstrates differential expression of two FXRα isoforms designated Fxrα1 and Fxrα2, in both free swimming medaka embryos with remaining yolk (eleutheroembryos, EEs) and adults. Activation of medaka Fxrα in vivo with GW4064 (a strong FXRα agonist) resulted in modification of gene expression for defined FXRα gene targets including the bile salt export protein, small heterodimer partner, and cytochrome P450 7A1. Histological examination of medaka liver subsequent to GW4064 exposure demonstrated significant lipid accumulation, cellular and organelle alterations in both hepatocytes and biliary epithelial cells of the liver. This report of hepatobiliary injury following GW4064 exposure extends previous investigations of the intrahepatic biliary system in medaka, reveals sensitivity to toxicant exposure, and illustrates the need for added resolution in detection and interpretation of toxic responses in this vertebrate.}, number={1}, journal={TOXICOLOGY AND APPLIED PHARMACOLOGY}, author={Howarth, Deanna L. and Law, Sheran H. W. and Law, J. McHugh and Mondon, J. A. and Kullman, Seth W. and Hinton, David E.}, year={2010}, month={Feb}, pages={111–121} }
 @article{yoon_kim_yi_kang_jang_joo_kim_law_kim_2010, title={Expression of thioredoxin during progression of hamster and human cholangiocarcinoma}, volume={101}, ISSN={["1349-7006"]}, DOI={10.1111/j.1349-7006.2009.01353.x}, abstractNote={Thioredoxin (Trx) is a multifunctional redox protein that has growth‐promoting and anti‐apoptotic effects on cells and protects cells from endogenous and exogenous free radicals. Recently, altered expression of Trx has been reported in various cancers. In the present study, we investigated altered expression of Trx at the precancerous and carcinogenic phases during cholangiocarcinogenesis in a hamster cholangiocarcinoma (ChC) model, using semiquantitative immunohistochemical and Western blot analyses. Moreover, to determine if the results correlated well with those in human ChCs, we carried out a comparative immunohistochemical study for Trx in tissue‐arrayed human ChCs with different grades of tumor cell differentiation. Trx was found highly expressed in the cytoplasm of dysplastic bile ducts with highly abnormal growth patterns and ChCs irrespective of tumor type or tumor cell differentiation. Overexpression of Trx at the precancerous and carcinogenic phases was further supported by significant elevation of Trx protein in Western blotting. The results from the hamster ChCs were in good agreement with those from human ChCs. Our results strongly suggested that the redox regulatory function of Trx plays an important role in bile duct cell transformation and tumor progression during cholangiocarcinogenesis. (Cancer Sci 2009)}, number={1}, journal={CANCER SCIENCE}, author={Yoon, Byung-Il and Kim, Yeong-Hun and Yi, Jung-Yeon and Kang, Min-Soo and Jang, Ja-June and Joo, Kyoung-Hwan and Kim, Yongbaek and Law, J. McHugh and Kim, Dae-Yong}, year={2010}, month={Jan}, pages={281–288} }
 @article{anderson_davis_law_lewbart_christian_harms_2010, title={Gross and histologic evaluation of 5 suture materials in the skin and subcutaneous tissue of the california sea hare (Aplysia californica)}, volume={49}, number={1}, journal={Journal of the American Association for Laboratory Animal Science}, author={Anderson, E. T. and Davis, A. S. and Law, J. M. and Lewbart, G. A. and Christian, L. S. and Harms, C. A.}, year={2010}, pages={64–68} }
 @article{lauren_hinton_law_sorensen_lyndall_magar_nielsen_2010, title={LONG-TERM TRENDS IN LIVER NEOPLASMS IN BROWN BULLHEAD IN THE BUFFALO RIVER, NEW YORK, USA}, volume={29}, ISSN={["1552-8618"]}, DOI={10.1002/etc.206}, abstractNote={Abstract}, number={8}, journal={ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY}, author={Lauren, Darrel J. and Hinton, David and Law, Mac and Sorensen, Mary and Lyndall, Jennifer and Magar, Victor and Nielsen, Mark}, year={2010}, month={Aug}, pages={1748–1754} }
 @article{hinton_hardman_kullman_law_schmale_walter_winn_yoder_2009, title={Aquatic animal models of human disease: Selected papers and recommendations from the 4th Conference}, volume={149}, ISSN={1532-0456}, url={http://dx.doi.org/10.1016/j.cbpc.2008.12.006}, DOI={10.1016/j.cbpc.2008.12.006}, abstractNote={Large volumes of oil sands process-affected water (OSPW) are produced by the surface-mining oil sands industry in Alberta. Both laboratory and field studies have demonstrated that the exposure to OSPW leads to many physiological changes in a variety of organisms. Adverse effects include compromised immunological function, developmental delays, impaired reproduction, disrupted endocrine system, and higher prevalence of tissue-specific pathological manifestations. The composition of OSPW varies with several factors such as ore sources, mining process, and tailings management practices. Differences in water characteristics have confounded interpretation or comparison of OSPW toxicity across studies. Research on individual fractions extracted from OSPW has helped identify some target pollutants. Naphthenic acids (NAs) are considered as the major toxic components in OSPW, exhibiting toxic effects through multiple modes of action including narcosis and endocrine disruption. Other pollutants, like polycyclic aromatic hydrocarbons (PAHs), metals, and ions may also contribute to the overall OSPW toxicity. Studies have been conducted on OSPW as a whole complex effluent mixture, with consideration of the presence of unidentified components, and the interactions (potential synergistic or antagonistic reactions) among chemicals. This review summarizes the toxicological data derived from in vitro and in vivo exposure studies using different OSPW types, and different taxa of organisms. In general, toxicity of OSPW was found to be dependent on the OSPW type and concentration, duration of exposures (acute versus sub chronic), and organism studied.}, number={2}, journal={Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology}, publisher={Elsevier BV}, author={Hinton, David E. and Hardman, Ron C. and Kullman, Seth W. and Law, Jerry M. and Schmale, Michael C. and Walter, Ronald B. and Winn, Richard N. and Yoder, Jeffrey A.}, year={2009}, month={Mar}, pages={121–128} }
 @article{freeman_lewbart_robarge_harms_law_stoskopf_2009, title={Characterizing eversion syndrome in captive scyphomedusa jellyfish}, volume={70}, ISSN={["0002-9645"]}, DOI={10.2460/ajvr.70.9.1087}, abstractNote={Abstract}, number={9}, journal={American Journal of Veterinary Research}, author={Freeman, K.S. and Lewbart, G.A. and Robarge, W.P. and Harms, C.A. and Law, J.M. and Stoskopf, M.K.}, year={2009}, month={Sep}, pages={1087–1093} }
 @article{jima_shah_orcutt_joshi_law_litman_trede_yoder_2009, title={Enhanced transcription of complement and coagulation genes in the absence of adaptive immunity}, volume={46}, ISSN={0161-5890}, url={http://dx.doi.org/10.1016/j.molimm.2008.12.021}, DOI={10.1016/j.molimm.2008.12.021}, abstractNote={A recessive nonsense mutation in the zebrafish recombination activating gene 1 (rag1) gene results in defective V(D)J recombination; however, animals homozygous for this mutation (rag1(-/-)) are reportedly viable and fertile in standard, nonsterile aquarium conditions but display increased mortality after intraperitoneal injection with mycobacteria. Based on their survival in nonsterile environments, we hypothesized that the rag1(-/-) zebrafish may possess an "enhanced" innate immune response to compensate for the lack of an adaptive immune system. To test this hypothesis, microarray analyses were used to compare the expression profiles of the intestines and hematopoietic kidneys of rag1 deficient zebrafish to the expression profiles of control (heterozygous) siblings. The expression levels of 12 genes were significantly altered in the rag1(-/-) kidney including the up regulation of a putative interferon stimulated gene, and the down regulation of genes encoding fatty acid binding protein 10, keratin 5 and multiple heat shock proteins. The expression levels of 87 genes were shown to be significantly altered in the rag1(-/-) intestine; the majority of these differences reflect increased expression of innate immune genes, including those of the coagulation and complement pathways. Subsequent analyses of orthologous coagulation and complement genes in Rag1(-/-) mice indicate increased transcription of the complement C4 gene in the Rag1(-/-) intestine.}, number={7}, journal={Molecular Immunology}, publisher={Elsevier BV}, author={Jima, Dereje D. and Shah, Radhika N. and Orcutt, Timothy M. and Joshi, Deepa and Law, J. McHugh and Litman, Gary W. and Trede, Nikolaus S. and Yoder, Jeffrey A.}, year={2009}, month={Apr}, pages={1505–1516} }
 @article{spitsbergen_blazer_bowser_cheng_cooper_cooper_frasca_groman_harper_law_et al._2009, title={Finfish and aquatic invertebrate pathology resources for now and the future}, volume={149}, ISSN={["1878-1659"]}, DOI={10.1016/j.cbpc.2008.10.002}, abstractNote={Utilization of finfish and aquatic invertebrates in biomedical research and as environmental sentinels has grown dramatically in recent decades. Likewise the aquaculture of finfish and invertebrates has expanded rapidly worldwide as populations of some aquatic food species and threatened or endangered aquatic species have plummeted due to overharvesting or habitat degradation. This increasing intensive culture and use of aquatic species has heightened the importance of maintaining a sophisticated understanding of pathology of various organ systems of these diverse species. Yet, except for selected species long cultivated in aquaculture, pathology databases and the workforce of highly trained pathologists lag behind those available for most laboratory animals and domestic mammalian and avian species. Several factors must change to maximize the use, understanding, and protection of important aquatic species: 1) improvements in databases of abnormalities across species; 2) standardization of diagnostic criteria for proliferative and nonproliferative lesions; and 3) more uniform and rigorous training in aquatic morphologic pathology.}, number={2}, journal={COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY}, author={Spitsbergen, Jan M. and Blazer, Vicki S. and Bowser, Paul R. and Cheng, Keith C. and Cooper, Keith R. and Cooper, Timothy K. and Frasca, Salvatore, Jr. and Groman, David B. and Harper, Claudia M. and Law, Jerry M. and et al.}, year={2009}, month={Mar}, pages={249–257} }
 @article{kent_feist_harper_hoogstraten-miller_law_sánchez-morgado_tanguay_sanders_spitsbergen_whipps_2009, title={Recommendations for control of pathogens and infectious diseases in fish research facilities}, volume={149}, ISSN={1532-0456}, url={http://dx.doi.org/10.1016/j.cbpc.2008.08.001}, DOI={10.1016/j.cbpc.2008.08.001}, abstractNote={Concerns about infectious diseases in fish used for research have risen along with the dramatic increase in the use of fish as models in biomedical research. In addition to acute diseases causing severe morbidity and mortality, underlying chronic conditions that cause low-grade or subclinical infections may confound research results. Here we present recommendations and strategies to avoid or minimize the impacts of infectious agents in fishes maintained in the research setting. There are distinct differences in strategies for control of pathogens in fish used for research compared to fishes reared as pets or in aquaculture. Also, much can be learned from strategies and protocols for control of diseases in rodents used in research, but there are differences. This is due, in part, the unique aquatic environment that is modified by the source and quality of the water provided and the design of facilities. The process of control of pathogens and infectious diseases in fish research facilities is relatively new, and will be an evolving process over time. Nevertheless, the goal of documenting, detecting, and excluding pathogens in fish is just as important as in mammalian research models.}, number={2}, journal={Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology}, publisher={Elsevier BV}, author={Kent, Michael L. and Feist, Stephen W. and Harper, Claudia and Hoogstraten-Miller, Shelley and Law, J. Mac and Sánchez-Morgado, José M. and Tanguay, Robert L. and Sanders, George E. and Spitsbergen, Jan M. and Whipps, Christopher M.}, year={2009}, month={Mar}, pages={240–248} }
 @article{hobbie_deangelo_king_winn_law_2009, title={Toward a molecular equivalent dose: Use of the medaka model in comparative risk assessment}, volume={149}, ISSN={1532-0456}, url={http://dx.doi.org/10.1016/j.cbpc.2008.07.013}, DOI={10.1016/j.cbpc.2008.07.013}, abstractNote={Recent changes in the risk assessment landscape underscore the need to be able to compare the results of toxicity and dose–response testing between a growing list of animal models and, quite possibly, an array of in vitro screening assays. How do we compare test results for a given compound between vastly different species? For example, what dose level in the ambient water of a small fish model would be equivalent to 10 ppm of a given compound in the rat's drinking water? Where do we begin? To initially address these questions, and in order to compare dose–response tests in a standard rodent model with a fish model, we used the concept of molecular dose. Assays that quantify types of DNA damage that are directly relevant to carcinogenesis integrate the factors such as chemical exposure, uptake, distribution, metabolism, etc. that tend to vary so widely between different phyletic levels. We performed parallel exposures in F344 rats and Japanese medaka (Oryzias latipes) to the alkylating hepatocarcinogen, dimethylnitrosamine (DMN). In both models, we measured the DNA adducts 8-hydroxyguanine, N7-methylguanine and O6-methylguanine in the liver; mutation frequency using λ cII transgenic medaka and λ cII transgenic (Big Blue®) rats; and early morphological changes in the livers of both models using histopathology and immunohistochemistry. Pulse dose levels in fish were 0, 10, 25, 50, or 100 ppm DMN in the ambient water for 14 days. Since rats are reported to be especially sensitive to DMN, they received 0, 0.1, 1, 5, 10, or 25 ppm DMN in the drinking water for the same time period. While liver DNA adduct concentrations were similar in magnitude, mutant frequencies in the DMN-exposed medaka were up to 20 times higher than in the Big Blue rats. Future work with other compounds will generate a more complete picture of comparative dose response between different phyletic levels and will help guide risk assessors using “alternative” models.}, number={2}, journal={Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology}, publisher={Elsevier BV}, author={Hobbie, Kristen R. and DeAngelo, Anthony B. and King, Leon C. and Winn, Richard N. and Law, J. McHugh}, year={2009}, month={Mar}, pages={141–151} }
 @article{harms_christian_burrus_hopkins_pandiri_law_wolf_butler_lewbart_2008, title={Cryotherapy for removal of a premaxillary mass from a chain pickerel using an over-the-counter wart remover}, volume={DVM 10}, journal={Exotic}, author={Harms, C.A. and Christian, L.S. and Burrus, O. and Hopkins, W.B. and Pandiri, A.K.R. and Law, J.M. and Wolf, K.N. and Butler, C.M. and Lewbart, G.A.}, year={2008}, pages={15–17} }
 @article{wooten_blikslager_ryan_marks_law_lascelles_2008, title={Cyclooxygenase expression and prostanoid production in pyloric and duodenal mucosae in dogs after administration of nonsteroidal anti-inflammatory drugs}, volume={69}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.69.4.457}, DOI={10.2460/ajvr.69.4.457}, abstractNote={Abstract}, number={4}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Wooten, Jenna G. and Blikslager, Anthony T. and Ryan, Kathleen A. and Marks, Steve L. and Law, J. Mac and Lascelles, B. Duncan X.}, year={2008}, month={Apr}, pages={457–464} }
 @inbook{law_elmore_2008, title={Mechanisms of Cell Death}, ISBN={9780470285251 9780470102114}, url={http://dx.doi.org/10.1002/9780470285251.ch16}, DOI={10.1002/9780470285251.ch16}, abstractNote={This chapter contains sections titled: Introduction How Cells/Tissues React to “Stress” Cell Injury and Cell Death Morphology of Cell Injury and Cell Death Apoptosis Suggested Reading}, booktitle={Molecular and Biochemical Toxicology}, publisher={John Wiley & Sons, Inc.}, author={Law, Mac and Elmore, Susan}, year={2008}, month={Jul}, pages={287–318} }
 @article{choi_lehmann_harms_law_2007, title={Acute hypoxia-reperfusion triggers immunocompromise in Nile tilapia}, volume={19}, ISSN={["1548-8667"]}, DOI={10.1577/H06-010.1}, abstractNote={Abstract}, number={2}, journal={JOURNAL OF AQUATIC ANIMAL HEALTH}, author={Choi, K. and Lehmann, D. W. and Harms, C. A. and Law, J. M.}, year={2007}, month={Jun}, pages={128–140} }
 @article{cachot_law_pottier_peluhet_norris_budzinski_winn_2007, title={Characterization of toxic effects of sediment-associated organic pollutants using the lambda transgenic medaka}, volume={41}, ISSN={["1520-5851"]}, DOI={10.1021/es071082v}, abstractNote={A novel sediment-contact assay using embryos of the transgenic medaka was developed to fully characterize the toxic effects induced by exposure to a mixture of organic pollutants in sediments. Embryos of the lambda transgenic medaka were exposed for 10 days to a clean reference sediment spiked with either the solvent alone, benzo[a]pyrene (B[a]P), or three concentrations (0.3x, 1x, and 2x) of an organic extract (OE) of sediments from the Seine estuary. The 1 x OE-spiked sediment contained concentrations of polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls similar to those in field-collected sediment. Exposure to this sediment, but not to the B[a]P-spiked sediment, significantly increased embryo-larval mortality and prevalence of spinal deformities. Mutant frequency at the cII mutation target gene in the liver of 10-week-old medaka was significantly increased following exposure to either B[a]P or the three doses of OE. The predominant OE-induced liver mutations were G:C to T:A transversions, consistent with PAHs being the major contributors to the mutation induction. Liver and gonadal tumors were observed in 35-week-old medaka exposed to either B[a]P (1/25) or to the 1 x OE (1/24). The benefits of medaka as a fish model for toxicological assessment and the benefits of the cII mutation assay for mutation detection combine to provide comprehensive assessment of a wide range of genotoxic and nongenotoxic effects of aquatic pollutants.}, number={22}, journal={ENVIRONMENTAL SCIENCE & TECHNOLOGY}, author={Cachot, Jerome and Law, Mac and Pottier, Didier and Peluhet, Laurent and Norris, Michelle and Budzinski, Helene and Winn, Richard}, year={2007}, month={Nov}, pages={7830–7836} }
 @article{johnson_law_harms_levine_2007, title={Multitiered Health Assessment of Atlantic Menhaden in the Pamlico River, North Carolina}, volume={19}, ISSN={0899-7659 1548-8667}, url={http://dx.doi.org/10.1577/H06-018.1}, DOI={10.1577/H06-018.1}, abstractNote={During the fall of 2001 and 2002, Atlantic menhaden Brevoortia tyrannus were collected from several creeks in the Pamlico River, North Carolina, to investigate recent fish kills and ulcerative skin lesions. High skin lesion prevalence (>50%) was associated with the Atlantic menhaden kills in fall 2001, whereas there were no fish kills in fall 2002 and skin lesion prevalence was lower (< or =50%). Indicators of tissue damage (histopathological analyses of gills, heart, liver, intestine, and anterior kidney), body condition (liver somatic index), and immune status (transforming growth factor-beta [TGF-beta] messenger RNA [mRNA] production, hematology, plasma chemistry, and splenosomatic index) were compared between Atlantic menhaden with and without ulcerative skin lesions in fall. Atlantic menhaden with ulcerative skin lesions had significantly higher liver somatic indices, neutrophil and monocyte percentages, and splenic mononuclear cell TGF-beta mRNA levels than did fish without lesions. Hematocrit values, plasma protein, and Ca concentrations were significantly lower in fish with ulcerative skin lesions than in those without. The indicators used in this study at multiple levels of biological organization have provided valuable baseline data for understanding the health status of lesioned and nonlesioned Atlantic menhaden in the Pamlico River.}, number={4}, journal={Journal of Aquatic Animal Health}, publisher={Wiley}, author={Johnson, A. K. and Law, J. M. and Harms, C. A. and Levine, J. F.}, year={2007}, month={Dec}, pages={205–214} }
 @article{lehmann_levine_law_2007, title={Polychlorinated Biphenyl Exposure Causes Gonadal Atrophy and Oxidative Stress in Corbicula fluminea Clams}, volume={35}, ISSN={0192-6233 1533-1601}, url={http://dx.doi.org/10.1080/01926230701230288}, DOI={10.1080/01926230701230288}, abstractNote={ Polychlorinated biphenyls (PCBs) are widespread environmental contaminants that have been linked to oxidative and other toxic effects in both humans and wildlife. Due to recent environmental health concerns at a PCB contaminated Superfund site near Raleigh, NC, we used a common clam species ( Corbicula fluminea) as surrogates to isolate the effects of PCBs on threatened bivalves native to the region. Under controlled laboratory conditions, clams were exposed to 0, 1, 10, or 100 ppb Aroclor 1260 in the ambient water for 21 days. Measured biomarkers spanned a range of effective levels of biological organization including low molecular weight antioxidants, lipid-soluble antioxidants, and whole tissue radical absorption capacity. These data were augmented by use of histological evaluation of whole samples. Aroclor 1260 significantly increased reduced glutathione (GSH) and total protein concentrations at all treatments levels. Significant decreases were measured in all treatments in γ-tocopherol and total oxidant scavenging capacity (TOSC) and α-tocopherol values in the 100 ppb exposure. Histologically, Aroclor 1260 caused significant gonadal atrophy, effacement of gonad architecture with accumulations of Brown cells, and inflammation and necrosis in digestive glands and foot processes. Our results indicate that oxidative mechanisms play a significant role in the decreased health of these clams due to exposure to Aroclor 1260. The changes in the gonads of exposed clams suggest that a serious threat to bivalve reproduction exists due to PCB exposure. }, number={3}, journal={Toxicologic Pathology}, publisher={SAGE Publications}, author={Lehmann, Daniel W. and Levine, Jay F. and Law, J. Mchugh}, year={2007}, month={Apr}, pages={356–365} }
 @article{johnson_harms_levine_law_2006, title={A quantitative real-time RT-PCR assay to measure TGF-β mRNA and its correlation with hematologic, plasma chemistry and organo-somatic indices responses in triamcinolone-treated Atlantic menhaden, Brevoortia tyrannus}, volume={30}, ISSN={0145-305X}, url={http://dx.doi.org/10.1016/j.dci.2005.06.021}, DOI={10.1016/j.dci.2005.06.021}, abstractNote={A quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) assay was developed to measure transforming growth factor-beta (TGF-beta) in Atlantic menhaden (Brevoortia tyrannus), an estuarine-dependent species plagued by ulcerative skin lesions in the estuaries along the eastern United States. Atlantic menhaden were acclimated in a closed system for two weeks prior to initiation of the study. The synthetic glucocorticoid, triamcinolone acetonide (10mg/kg body weight) was administered by intracoelomic injection and its effect on the splenic mononuclear cell TGF-beta mRNA transcription, liver-somatic index, spleno-somatic index, hematology, and plasma chemistry were compared to untreated fish at 48 and 96h post-treatment. Triamcinolone-treated Atlantic menhaden showed suppression of TGF-beta mRNA production, neutrophilia, monocytosis, lymphopenia, and an increase in blood glucose concentrations. The health indices used in this study may help us interpret some of the changes observed during the development of ulcerative skin lesions in wild-caught menhaden.}, number={5}, journal={Developmental & Comparative Immunology}, publisher={Elsevier BV}, author={Johnson, A.K. and Harms, C.A. and Levine, J.F. and Law, J. McHugh}, year={2006}, month={Jan}, pages={473–484} }
 @inbook{levine_law_corsin_2006, place={Ames, Iowa}, title={Chapter 7: Bivalves}, booktitle={Invertebrate Medicine}, publisher={Blackwell Publishing}, author={Levine, J.F. and Law, M. and Corsin, F.}, editor={Lewbart, G.Editor}, year={2006}, pages={91–115} }
 @article{volz_hinton_law_kullman_2006, title={Dynamic Gene Expression Changes Precede Dioxin-Induced Liver Pathogenesis in Medaka Fish}, volume={89}, ISSN={1096-6080 1096-0929}, url={http://dx.doi.org/10.1093/toxsci/kfj033}, DOI={10.1093/toxsci/kfj033}, abstractNote={A major challenge for environmental genomics is linking gene expression to cellular toxicity and morphological alteration. Herein, we address complexities related to hepatic gene expression responses after a single injection of the aryl hydrocarbon receptor (AHR) agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) and illustrate an initial stress response followed by cytologic and adaptive changes in the teleost fish medaka. Using a custom 175-gene array, we find that overall hepatic gene expression and histological changes are strongly dependent on dose and time. The most pronounced dioxin-induced gene expression changes occurred early and preceded morphologic alteration in the liver. Following a systematic search for putative Ah response elements (AHREs) (5'-CACGCA-3') within 2000 bp upstream of the predicted transcriptional start site, the majority (87%) of genes screened in this study did not contain an AHRE, suggesting that gene expression was not solely dependent on AHRE-mediated transcription. Moreover, in the highest dosage, we observed gene expression changes associated with adaptation that persisted for almost two weeks, including induction of a gene putatively identified as ependymin that may function in hepatic injury repair. These data suggest that the cellular response to dioxin involves both AHRE- and non-AHRE-mediated transcription, and that coupling gene expression profiling with analysis of morphologic pathogenesis is essential for establishing temporal relationships between transcriptional changes, toxicity, and adaptation to hepatic injury.}, number={2}, journal={Toxicological Sciences}, publisher={Oxford University Press (OUP)}, author={Volz, David C. and Hinton, David E. and Law, J. McHugh and Kullman, Seth W.}, year={2006}, month={Feb}, pages={524–534} }
 @article{tuttle_law_harms_lewbart_harvey_2006, title={Evaluation of the gross and histologic reactions to five commonly used suture materials in the skin of the African clawed frog (Xenopus laevis)}, volume={45}, number={6}, journal={Journal of the American Association for Laboratory Animal Science}, author={Tuttle, A. D. and Law, J. M. and Harms, C. A. and Lewbart, G. A. and Harvey, S. B.}, year={2006}, pages={22–26} }
 @article{volz_bencic_hinton_law_kullman_2005, title={2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) Induces Organ- Specific Differential Gene Expression in Male Japanese Medaka (Oryzias latipes)}, volume={85}, ISSN={1096-6080 1096-0929}, url={http://dx.doi.org/10.1093/toxsci/kfi109}, DOI={10.1093/toxsci/kfi109}, abstractNote={2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitous environmental contaminant with well-known adverse effects in fish. In this study, we initially exploited suppression subtractive hybridization (SSH) as a screening tool to assess qualitative gene expression changes in whole brain, liver, and testis of adult male Japanese medaka (Oryzias latipes) exposed for 48 h to a single intraperitoneal-injected dose of TCDD (10 microg TCDD/kg body weight). Across these three organs, SSH identified a total of 335 unique genes. Each set of forward- and reverse-subtracted organ cDNA libraries consisted of a distinct gene list and corresponding distribution of biological processes, suggesting that transcript profiles of these libraries were highly organ-specific. Based on sequence match significance and frequencies within each set of organ libraries, genes hypothesized to be strongly responsive (42 total) within male medaka brain, liver, or testis were semi-quantitatively screened with replicate cDNA nylon membrane arrays. In addition, TCDD-treated male medaka were surveyed for gross histological analysis of brain, liver, and testis. In general, adverse histopathological changes were not observed in the brain, and glycogen depletion was observed only in the liver. However, significant histological changes occurred in the testis, and included disorganization of spermatogenesis at the testis periphery, disruption of the interstitium, Leydig cell swelling, and Sertoli cell vacuolation. Of the 42 genes screened by cDNA array analysis, cytochrome P450 1A (CYP1A) mRNA was the only transcript significantly higher in TCDD-exposed brain, whereas 12 transcripts (including CYP1A) were significantly higher in TCDD-exposed liver, and 34 transcripts were significantly lower in TCDD-exposed testis. Therefore, the degree of TCDD-induced alterations observed in each organ at a gross histological level corresponded well with the number and ontology of gene transcripts affected on the array. Based on real-time reverse transcription polymerase chain reaction (RT-PCR), relative CYP1A (but not AHR1) transcript levels were confirmed to be significantly higher in TCDD-treated brain and liver. However, CYP1A was not significantly induced in TCDD-exposed testis, suggesting that gene expression and histopathological responses observed in the testis at 48 h may be CYP1A-independent. Based on these data, unique liver-specific and testis-specific mRNA-level targets in male medaka were identified as promising biomarkers of acute TCDD-induced toxicity.}, number={1}, journal={Toxicological Sciences}, publisher={Oxford University Press (OUP)}, author={Volz, David C. and Bencic, David C. and Hinton, David E. and Law, J. McHugh and Kullman, Seth W.}, year={2005}, month={Feb}, pages={572–584} }
 @article{burkholder_gordon_moeller_law_coyne_lewitus_ramsdell_marshall_deamer_cary_et al._2005, title={Demonstration of toxicity to fish and to mammalian cells by Pfiesteria species: Comparison of assay methods and strains}, volume={102}, ISSN={0027-8424 1091-6490}, url={http://dx.doi.org/10.1073/pnas.0500168102}, DOI={10.1073/pnas.0500168102}, abstractNote={
            Toxicity and its detection in the dinoflagellate fish predators
            Pfiesteria piscicida
            and
            Pfiesteria shumwayae
            depend on the strain and the use of reliable assays. Two assays, standardized fish bioassays (SFBs) with juvenile fish and fish microassays (FMAs) with larval fish, were compared for their utility to detect toxic
            Pfiesteria
            . The comparison included strains with confirmed toxicity, negative controls (noninducible
            Pfiesteria
            strains and a related nontoxic cryptoperidiniopsoid dinoflagellate), and
            P. shumwayae
            strain CCMP2089, which previously had been reported as nontoxic. SFBs, standardized by using toxic
            Pfiesteria
            (coupled with tests confirming
            Pfiesteria
            toxin) and conditions conducive to toxicity expression, reliably detected actively toxic
            Pfiesteria
            , but FMAs did not.
            Pfiesteria
            toxin was found in fish- and algae-fed clonal
            Pfiesteria
            cultures, including CCMP2089, but not in controls. In contrast, noninducible
            Pfiesteria
            and cryptoperidiniopsoids caused no juvenile fish mortality in SFBs even at high densities, and low larval fish mortality by physical attack in FMAs. Filtrate from toxic strains of
            Pfiesteria
            spp. in bacteria-free media was cytotoxic. Toxicity was enhanced by bacteria and other prey, especially live fish. Purified
            Pfiesteria
            toxin extract adversely affected mammalian cells as well as fish, and it caused fish death at environmentally relevant cell densities. These data show the importance of testing multiple strains when assessing the potential for toxicity at the genus or species level, using appropriate culturing techniques and assays.
          }, number={9}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Burkholder, J. M. and Gordon, A. S. and Moeller, P. D. and Law, J. M. and Coyne, K. J. and Lewitus, A. J. and Ramsdell, J. S. and Marshall, H. G. and Deamer, N. J. and Cary, S. C. and et al.}, year={2005}, month={Feb}, pages={3471–3476} }
 @article{adams_greeley_law_noga_zelikoff_2003, title={Application of multiple sublethal stress indicators to assess the health of fish in Pamlico Sound following extensive flooding}, volume={26}, DOI={10.1007/BF02803638}, number={5}, journal={Estuaries}, author={Adams, S. M. and Greeley, M. S. and Law, J. M. and Noga, E. J. and Zelikoff, J. T.}, year={2003}, pages={1365–1382} }
 @article{savary-bataille_bunch_spaulding_jackson_mac law_stebbins_2003, title={Percutaneous ultrasound-guided cholecystocentesis in healthy cats}, volume={17}, ISSN={["1939-1676"]}, DOI={10.1892/0891-6640(2003)017<0298:PUCIHC>2.3.CO;2}, number={3}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Savary-Bataille, KCM and Bunch, SE and Spaulding, KA and Jackson, MW and Mac Law, J and Stebbins, ME}, year={2003}, pages={298–303} }
 @article{hurty_brazik_law_sakamoto_lewbart_2002, title={Evaluation of the tissue reactions in the skin and body wall of koi (Cyprinus carpio) to five suture materials}, volume={151}, ISSN={["0042-4900"]}, DOI={10.1136/vr.151.11.324}, abstractNote={Five different suture materials (silk, monofilament nylon, polyglyconate, polyglactin 910, and chromic gut) were placed in the skin and body wall of 10 Doitsu (scaleless) koi (Cyprinus carpio). After seven days the sutures were retrieved from five of the fish in 5 mm and 6 mm punch biopsies, and after 14 days they were retrieved in the same way from the other five. The tissue reactions were evaluated by gross visual inspection and by histological examination. The total inflammatory reaction was graded on a scale from 0 (no inflammation) to 5 (severe inflammation). The synthetic suture materials generally induced a moderate inflammatory reaction that decreased after seven days. After 14 days the superficial reaction to monofilament nylon was substantial, and the tissue reactions to the organic suture materials were slightly greater than the reactions to the synthetics. The inflammatory response to silk was greater after 14 days than after seven, and chromic gut induced a moderately severe inflammatory response after seven days; the chromic gut sutures fell out before the biopsies were taken after 14 days. The organic materials induced intense inflammatory reactions which did not subside if the suture remained in the tissue.}, number={11}, journal={VETERINARY RECORD}, author={Hurty, CA and Brazik, DC and Law, JM and Sakamoto, K and Lewbart, GA}, year={2002}, month={Sep}, pages={324-+} }
 @article{pressler_rotstein_law_rosol_leroy_keene_jackson_2002, title={Hypercalcemia and high parathyroid hormone-related protein concentration associated with malignant melanoma in a dog}, volume={221}, ISSN={["0003-1488"]}, DOI={10.2460/javma.2002.221.263}, abstractNote={A 12-year-old Cocker Spaniel with an oral malignant melanoma was evaluated for progressive lethargy and anorexia. No metastases were identified during antemortem evaluation, but severe hypercalcemia was evident. Antemortem diagnostic testing failed to identify a cause for the hypercalcemia. No neoplasms other than the melanoma were identified on postmortem examination. Serum parathyroid hormone-related protein concentration was markedly high, and the melanoma had moderate to marked immunostaining for this protein. Paraneoplastic syndromes are rare in dogs with malignant melanoma.}, number={2}, journal={JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Pressler, BM and Rotstein, DS and Law, JM and Rosol, TJ and LeRoy, B and Keene, BW and Jackson, MW}, year={2002}, month={Jul}, pages={263-+} }
 @article{jaeger_rotstein_law_2002, title={Prostatic pythiosis in a dog}, volume={16}, ISSN={["0891-6640"]}, DOI={10.1892/0891-6640(2002)016<0598:PPIAD>2.3.CO;2}, abstractNote={Journal of Veterinary Internal MedicineVolume 16, Issue 5 p. 598-602 Open Access Prostatic Pythiosis in a Dog Gayle H. Jaeger, Corresponding Author Gayle H. Jaeger Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC. Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606; e-mail: [email protected]Search for more papers by this authorDavid S. Rotstein, David S. Rotstein Department of Microbiology, Pathology, and Parasitology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC.Search for more papers by this authorJ. McHugh Law, J. McHugh Law Department of Microbiology, Pathology, and Parasitology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC.Search for more papers by this author Gayle H. Jaeger, Corresponding Author Gayle H. Jaeger Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC. Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606; e-mail: [email protected]Search for more papers by this authorDavid S. Rotstein, David S. Rotstein Department of Microbiology, Pathology, and Parasitology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC.Search for more papers by this authorJ. McHugh Law, J. McHugh Law Department of Microbiology, Pathology, and Parasitology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC.Search for more papers by this author First published: 28 June 2008 https://doi.org/10.1111/j.1939-1676.2002.tb02394.xCitations: 14AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL References 1 Laflamme DP. Body condition scoring and weight maintenance. Proceedings of the North American Veterinary Conference, Orlando, FL, January 16–21, 1993. 2 Grooters AM, Lopez MK, Brown AK, et al. Production of poly-clonal antibodies for the immunohistochemical identification of Pyth-ium insidiosum. 19th Annual Veterinary Forum, American College of Veterinary Internal Medicine, Denver, CO, 2001. 3 Grooters AM, Gee MK. Development of a nested PCR assay for the detection and identification of Pythium insidiosum. J Vet Intern Med 2002; 16: 147– 152. 4 Miller RI. Gastrointestinal phycomycosis in 63 dogs. J Am Vet Med Assoc 1985; 186: 473– 478. 5 Thomas RC, Lewis DT. Pythiosis in dogs and cats. Compend Cont Educ Pract Vet 1998; i: 63– 72. 6 Dykstra MJ, Sharp NJ, Olivry T., et al. A description of cutaneous-subcutaneous pythiosis in fifteen dogs. Med Mycol 1999; 37: 427– 433. 7 Fisher JR, Pace LW, Turk JR, et al. Gastrointestinal pythiosis in Missouri dogs: Eleven cases. J Vet Diagn Invest 1994; 6: 380– 382. 8 Helman RG, Oliver J. Pythiosis of the digestive tract in dogs from Oklahoma. J Am Anim Hosp Assoc 1999; 35: 111– 114. 9 Foil CS. Miscellaneous fungal diseases. In: CE Green, ed. Infectious Diseases of the Dog and Cat, 2nd ed. Philadelphia , PA : WB Saunders; 1998: 420– 430. 10 Cooper RC, Allison N., Boring JG. Apparent successful surgical treatment of intestinal pythiosis with vascular invasion in a dog. Canine Pract 1991; 16: 9– 12. 11 Patton CS, Hake R., Newton, et al. Esophagitis due to Pythium insidiosum infection in two dogs. J Vet Intern Med 1996; 10: 139– 142. 12 Ader PL. Phycomycosis in fifteen dogs and two cats. J Am Vet Med Assoc 1979; 174: 1216– 1223. 13 Pavletic MM, Miller RI, Turnwald GH. Intestinal infarction associated with canine phycomycosis. J Am Anim Hosp Assoc 1983; 19: 1227– 1229. 14 Bissonnette KW, Sharp NJ, Dykstra MH, et al. Nasal and ret-robulbar mass in a cat caused by Pythium insidiosum. J Med Vet Mycol 1991; 29: 39– 44. 15 Chaffin MK, Schumaker J., McMullan WC. Cutaneous pythiosis in the horse. Vet Clin North Am Equine Pract 1995; 11: 91– 103. Citing Literature Volume16, Issue5September 2002Pages 598-602 ReferencesRelatedInformation}, number={5}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Jaeger, GH and Rotstein, DS and Law, JM}, year={2002}, pages={598–602} }
 @article{savary_sellon_law_2001, title={Chylous abdominal effusion in a cat with feline infectious peritonitis}, volume={37}, ISSN={["0587-2871"]}, DOI={10.5326/15473317-37-1-35}, abstractNote={A 10-year-old cat was diagnosed with chyloperitoneum based on the effusion characteristics. Feline coronavirus serology was positive. The owner declined further evaluation and elected euthanasia. Necropsy revealed vasculitis with multifocal areas of necrosis and lymphocytic-plasmacytic inflammation in multiple solid organs, most likely due to feline infectious peritonitis (FIP). Immunohistochemistry was negative for FIP antigen. Notwithstanding, the final diagnosis of FIP was based on the characteristic histopathological lesions. Underlying causes of chyloperitoneum in cats and humans are discussed, and possible pathogenesis of the chyloperitoneum in association with a vasculitis such as FIP is discussed.}, number={1}, journal={JOURNAL OF THE AMERICAN ANIMAL HOSPITAL ASSOCIATION}, author={Savary, KCM and Sellon, RK and Law, JM}, year={2001}, pages={35–40} }
 @article{law_2001, title={Differential diagnosis of ulcerative lesions in fish}, volume={109}, ISSN={["1552-9924"]}, DOI={10.2307/3454913}, journal={ENVIRONMENTAL HEALTH PERSPECTIVES}, author={Law, M}, year={2001}, month={Oct}, pages={681–686} }
 @article{gookin_levy_law_papich_poore_breitschwerdt_2001, title={Experimental infection of cats with Tritrichomonas foetus}, volume={62}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.2001.62.1690}, DOI={10.2460/ajvr.2001.62.1690}, abstractNote={Abstract}, number={11}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Gookin, Jody L. and Levy, Michael G. and Law, J. Mac and Papich, Mark G. and Poore, Matthew F. and Breitschwerdt, Edward B.}, year={2001}, month={Nov}, pages={1690–1697} }
 @article{law_lopez_deangelo_1998, title={Hepatotoxicity of the drinking water disinfection by-product, dichloroacetic acid, in the medaka small fish model}, volume={94}, ISSN={["1879-3169"]}, DOI={10.1016/s0378-4274(97)00095-7}, abstractNote={Recent studies have shown that dichloroacetic acid (DCA), a by-product of chlorination of public water supplies, is carcinogenic to both rats and mice. However, conflicting data have left the mechanism of DCA carcinogenicity, vital to assessment of human health risk, unclear. Elucidation of this mechanism in another animal model at a different phyletic level than rodents would advance the risk assessment process for government agencies concerned with regulation and provision of safe drinking water. The Japanese medaka (Oryzias latipes), a well characterized small fish model, is being used increasingly for carcinogenicity testing because of its low cost, ease of maintenance and carcinogen sensitivity. In this study, 6-week-old medaka were exposed to diethylnitrosamine (DEN, a known initiator), followed by continuous exposure to 0.5 or 2.0 g/l DCA in the ambient water, over a 4 week period. At both exposure concentrations, changes in the liver included marked hepatocellular cytoplasmic vacuolation, cytomegaly, karyomegaly, nuclear atypia and multifocal areas of hepatocellular necrosis and loss as early as week two of DCA exposure. The majority of the hepatocellular cytoplasmic vacuoles were shown by periodic acid Schiff (PAS) staining to contain large amounts of glycogen. These elevated glycogen levels may reflect a disruption in the enzyme pathways for glycolysis. The total cellular changes seen in this short-term exposure regimen are compatible with preneoplastic changes seen in rats and mice exposed to DCA. The results of this study strengthen the role of the Japanese medaka as a suitable species in carcinogenicity testing as well as its implementation in the risk assessment process for DCA across several phyletic levels.}, number={1}, journal={TOXICOLOGY LETTERS}, author={Law, JM and Lopez, L and DeAngelo, AB}, year={1998}, month={Jan}, pages={19–27} }
 @article{law_bull_nakamura_swenberg_1998, title={Molecular dosimetry of DNA adducts in the medaka small fish model}, volume={19}, ISSN={["0143-3334"]}, DOI={10.1093/carcin/19.3.515}, abstractNote={Small fish models are being used with increasing frequency for carcinogenicity testing and comparative cancer research in the US, Canada and Europe. However, there is a need to further define the early biochemical events of carcinogenesis in these species. Identification and quantitation of DNA adducts can integrate all of the various factors involved in chemical exposure, uptake, distribution and biotransformation of a putative carcinogen. In the present study, Japanese medaka (Oryzias latipes) were exposed to the alkylating agent, diethylnitrosamine (DEN), in the ambient water. Liver DNA was analyzed for O6-ethylguanine (O6EG), O4-ethylthymidine (O4ET) and O2-ethylthymidine (O2ET) by the immuno-slot-blot technique, using monoclonal antibodies against each adduct of interest. While fish exposed to 10 p.p.m. DEN had liver DNA adduct concentrations at or only slightly higher than background levels, those exposed to 100 p.p.m. DEN averaged 34 and 53 pmol O6EG/micromol guanine, 15 and 41 pmol O2ET/micromol thymidine and 2 and 6 pmol O4ET/micromol thymidine at 0 and 24 h post-exposure, respectively. The results of this study show that, under these short-term exposure conditions, ethyl-DNA adducts appear to accumulate in medaka liver tissue in a sublinear (i.e. non-linear) fashion after aqueous exposure to DEN. Thus, critical DNA repair enzymes such as O6-alkylguanine DNA alkyltransferase, which are relatively efficient at lower carcinogen levels, are probably saturated at the 100 p.p.m. concentration level of DEN.}, number={3}, journal={CARCINOGENESIS}, author={Law, JM and Bull, M and Nakamura, J and Swenberg, JA}, year={1998}, month={Mar}, pages={515–518} }