@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={A wild caught white catfish (Ameiurus catus Linnaeus) developed multiple cutaneous masses. Cytology revealed neoplastic lymphocytes and microscopy confirmed dermal infiltration with epitheliotropism in the epidermis, oral mucosa, and cornea, without internal organ involvement. Transmission electron microscopy did not identify viral particles. Histopathology supported cutaneous epitheliotropic lymphosarcoma, a condition most commonly reported in mammals. This is the first reported case of cutaneous epitheliotropic lymphosarcoma in an ictalurid and one of the few published cases of this condition in any fish species.}, 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"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85116074576&partnerID=MN8TOARS}, DOI={10.1002/vrc2.196}, abstractNote={Abstract An 8‐month‐old female entire Labradoodle was referred for further management of severe non‐cardiogenic pulmonary oedema after an accidental intravenous injection of the arsenical compound melarsomine. On arrival, the dog was non‐ambulatory, obtunded and in severe respiratory distress. Due to profound hypoxaemia despite oxygen supplementation, the dog was intubated and mechanically ventilated. While anaesthetised, the dog experienced three episodes of cardiac arrest with return of spontaneous circulation after cardiopulmonary resuscitation. However, due to continued severe hypoxaemia and haemodynamic instability, euthanasia was elected by the owners. On necropsy, marked pulmonary oedema and haemorrhage into multiple organs, including the endocardium and brain, were identified. Although no other reports describe the consequences of intravenous melarsomine in dogs, the postmortem findings are very similar to intravenous arsenic toxicity in humans. Furthermore, this case report highlights the importance of accurate drug labelling.}, number={4}, 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 for Limulus polyphemus or 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={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 The vertebrate immune response comprises multiple molecular and cellular components that interface to provide defense against pathogens. Because of the dynamic complexity of the immune system and its interdependent innate and adaptive functionality, an understanding of the whole-organism response to pathogen exposure remains unresolved. Zebrafish larvae provide a unique model for overcoming this obstacle, because larvae are protected against pathogens while lacking a functional adaptive immune system during the first few weeks of life. Zebrafish larvae were exposed to immune agonists for various lengths of time, and a microarray transcriptome analysis was executed. This strategy identified known immune response genes, as well as genes with unknown immune function, including the E3 ubiquitin ligase tripartite motif-9 (Trim9). Although trim9 expression was originally described as “brain specific,” its expression has been reported in stimulated human Mϕs. In this study, we found elevated levels of trim9 transcripts in vivo in zebrafish Mϕs after immune stimulation. Trim9 has been implicated in axonal migration, and we therefore investigated the impact of Trim9 disruption on Mϕ motility and found that Mϕ chemotaxis and cellular architecture are subsequently impaired in vivo. These results demonstrate that Trim9 mediates cellular movement and migration in Mϕs as well as neurons.}, 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={Male fish are susceptible to developing intersex, a condition characterized by the presence of testicular oocytes. In the present study, the relationship between intersex and exposure to estrogenic endocrine active contaminants (EACs) was assessed for 2 genera of sport fish, Micropterus and Lepomis, at 20 riverine sites. Seasonal trends and relationships between EACs and intersex (prevalence and severity) were examined at varying putative sources of EACs throughout North Carolina, identified as point sources, nonpoint sources, and reference sites. Intersex was identified in both genera, which was documented for the first time in wild-caught Lepomis. Intersex was more prevalent (59.8%) and more severe (1.6 mean rank) in Micropterus, which was highly correlation to EACs in sediment. In contrast, intersex was less common (9.9%) and less severe (0.2 mean rank) in Lepomis and was highly correlated to EACs in the water column. The authors found that concentrations of polycyclic aromatic hydrocarbons, polychlorinated biphenyls, industrial EACs, and estrogens were highest at point source sites; however, no source type variation was identified in the prevalence or severity of intersex, nor were there seasonal trends in intersex or EAC concentrations. The authors' results associate genus-specific prevalence of intersex with specific EAC classes in common sport fishes having biological, ecological, and conservation implications. Environ Toxicol Chem 2017;36:959-968. © 2016 SETAC.}, 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 Monogenean parasite infestations are common in captive marine teleosts, and are generally found on the skin and gills. This report describes an unusual pathological presentation of exuberant granulation tissue of the gills, suspected to be related to Neobenedenia infestation in two cobia housed together at a North Carolina aquarium.}, 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 (1)H nuclear magnetic resonance spectroscopy to describe key metabolites of the polar metabolome of the freshwater mussel, Elliptio complanata. Principal components analysis documented variability across tissue types and river of origin in mussels collected from two rivers in North Carolina (USA). Muscle, digestive gland, mantle and gill tissues yielded identifiable but overlapping metabolic profiles. Variation in digestive gland metabolic profiles between the two mussel collection sites was characterized by differences in mono- and disaccharides. Variation in mantle tissue metabolomes appeared to be associated with sex. Nuclear magnetic resonance spectroscopy is a sensitive means to detect metabolites in the tissues of E. complanata and holds promise as a tool for the investigation of freshwater mussel health and physiology.}, 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={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={The presence of endocrine-disrupting compounds (EDCs), particularly estrogenic compounds, in the environment has drawn public attention across the globe, yet a clear understanding of the extent and distribution of estrogenic EDCs in surface waters and their relationship to potential sources is lacking. The objective of the present study was to identify and examine the potential input of estrogenic EDC sources in North Carolina water bodies using a geographic information system (GIS) mapping and analysis approach. Existing data from state and federal agencies were used to create point and nonpoint source maps depicting the cumulative contribution of potential sources of estrogenic EDCs to North Carolina surface waters. Water was collected from 33 sites (12 associated with potential point sources, 12 associated with potential nonpoint sources, and 9 reference), to validate the predictive results of the GIS analysis. Estrogenicity (measured as 17β-estradiol equivalence) ranged from 0.06 ng/L to 56.9 ng/L. However, the majority of sites (88%) had water 17β-estradiol concentrations below 1 ng/L. Sites associated with point and nonpoint sources had significantly higher 17β-estradiol levels than reference sites. The results suggested that water 17β-estradiol was reflective of GIS predictions, confirming the relevance of landscape-level influences on water quality and validating the GIS approach to characterize such relationships.}, 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={There is an important need for objective parameters that accurately predict the outcome of horses with large colon volvulus.To evaluate the predictive value of a series of histomorphometric parameters on short-term outcome, as well as the impact of colonic resection on horses with large colon volvulus.Retrospective cohort study.Adult horses admitted to the Equine and Farm Animal Veterinary Center at North Carolina State University, Peterson and Smith and Chino Valley Equine Hospitals between 2006 and 2013 that underwent an exploratory coeliotomy, diagnosed with large colon volvulus of ≥360 degrees, where a pelvic flexure biopsy was obtained, and that recovered from general anaesthesia, were selected for inclusion in the study. Logistic regression was used to determine associations between signalment, histomorphometric measurements of interstitium-to-crypt ratio, degree of haemorrhage, percentage loss of luminal and glandular epithelium, as well as colonic resection with short-term outcome (discharge from the hospital).Pelvic flexure biopsies from 47 horses with large colon volvulus were evaluated. Factors that were significantly associated with short-term outcome on univariate logistic regression were Thoroughbred breed (P = 0.04), interstitium-to-crypt ratio >1 (P = 0.02) and haemorrhage score ≥3 (P = 0.005). Resection (P = 0.92) was not found to be associated significantly with short-term outcome. No combined factors increased the likelihood of death in forward stepwise logistic regression modelling. A digitally quantified measurement of haemorrhage area strengthened the association of haemorrhage with nonsurvival in cases of large colon volvulus.Histomorphometric measurements of interstitium-to-crypt ratio and degree of haemorrhage predict short-term outcome in cases of large colon volvulus. Resection was not associated with short-term outcome in horses selected for this study. Accurate quantification of mucosal haemorrhage at the time of surgery may improve veterinary surgeons' prognostic capabilities in horses with large colon volvulus.}, 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={Background Tramadol is a centrally acting analgesic that is often used in conjunction with nonsteroidal anti‐inflammatory drugs ( NSAID s). The effect of coadministration of tramadol and indomethacin on gastric barrier function in dogs is unknown. Hypothesis/Objectives That coadministration of a nonselective NSAID (indomethacin) and tramadol would decrease recovery of barrier function as compared with acid‐injured, indomethacin‐treated, and tramadol‐treated mucosa. Animals Gastric mucosa of 10 humanely euthanized shelter dogs. Methods Ex vivo study. Mounted gastric mucosa was treated with indomethacin, tramadol, or both. Gastric barrier function, prostanoid production, and cyclooxygenase expression were quantified. Results Indomethacin decreased recovery of transepithelial electrical resistance after injury, although neither tramadol nor the coadministration of the two had an additional effect. Indomethacin inhibited production of gastroprotective prostanoids prostaglandin E 2 (acid‐injured PGE 2 : 509.3 ± 158.3 pg/mL, indomethacin + acid injury PGE 2 : 182.9 ± 93.8 pg/mL, P < .001) and thromboxane B 2 (acid‐injured TXB 2 : 233.2 ± 90.7 pg/mL, indomethacin + acid injury TXB 2 : 37.9 ± 16.8 pg/mL, P < .001), whereas tramadol had no significant effect ( PGE 2 P = .713, TXB 2 P = .194). Neither drug had an effect on cyclooxygenase expression ( COX ‐1 P = .743, COX ‐2 P = .705). Acid injury induced moderate to marked epithelial cell sloughing, which was unchanged by drug administration. Conclusions and Clinical Importance There was no apparent interaction of tramadol and a nonselective cyclooxygenase in this ex vivo model. These results suggest that if there is an adverse interaction of the 2 drugs in vivo, it is unlikely to be via prostanoid inhibition.}, 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={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={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 An aquaculture research facility experienced high mortality rates in white bass Morone chrysops associated with a monogenean infestation of the gills, but not in striped bass Morone saxatilis in the same facility. All mortalities had pale gills. Monogeneans, identified as Gamacallum macroura (MacCallum and MacCallum 1913) Unnithan 1971, were found on the gills. Pale-gilled and healthy white bass were selected with no particular attention to condition for venipuncture and euthanasia for postmortem examination, including parasite counts from gills. The median packed cell volume (PCV) of fish with gill pallor was 12.5% (range 9–37%) while PVC of fish with more normal color was 30% (27–33%). Association between the PCV and gill pallor score was statistically significant, as was the association between PCV and the number of monogeneans found on the gills of each fish. Median estimated white blood cell count of fish with gill pallor, at 12.05 × 103/μL (range 3.8–24.7), was significantly lower than of apparently healthy fish: 24.7 × 103/μL (17.3–31.5). Histopathology of the gill arches of pale-gilled fish revealed multifocal moderate to severe branchitis, focal areas of dilated hyperplastic lamellae occluded by fibrin, and monogeneans attached to the lamellae. Fish that were apparently healthy had grossly similar histologic lesions, but at lower frequency and severity. Received May 27, 2011; accepted July 12, 2012}, 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 Rapid changes in salinity, as with other environmental stressors, can have detrimental effects on fish and may trigger increased susceptibility to disease. However, the precise mechanisms of these effects are not well understood. We examined the effects of sudden increases or decreases in salinity on teleost immune function using N ile tilapia, O reochromis niloticus (L.), as the fish model in a battery of bioassays of increasing immune system specificity. Two different salinity experiments were performed: one of increasing salinity (0 to 5, 10 and 20 g L −1 ) and one of decreasing salinity (20 to 15, 10 and 5 g L −1 ). Histopathology of anterior kidney, gills, gonads, intestines and liver of exposed fish was performed, but no remarkable lesions were found that were attributable to the salinity treatment regimes. The spleen was removed from each fish for analysis of cytokine expression, and peripheral blood was used for haematology, cortisol and phagocytosis assays. In the increasing salinity experiments, no significant changes were observed in any immune system assays. However, in the decreasing salinity experiments, lymphopenia, neutrophilia and monocytosis were observed in the peripheral blood without modification of the packed cell volume, plasma protein or plasma cortisol levels. Phagocytosis was increased in response to decreases in salinity from 20 g L −1 to 15 g L −1 , 10 g L −1 and 5 g L −1 , whereas phagocytic index was not significantly altered. Transforming growth factor‐β ( TGF ‐β) transcription increased during the same decreases in salinity. However, the TGF ‐β value at 5 g L −1 was less than those in the 15 and 10 g L −1 salinity treatments. Interleukin‐1β ( IL ‐1β) transcription did not significantly respond to either salinity regime. In total, acute salinity changes appeared to trigger reactive dysregulation of the immune response in tilapia, a situation which, when combined with additional co‐occurring stressors such as sudden changes in temperature and/or dissolved oxygen, could make fish more susceptible to infectious diseases. Accordingly, these findings may help to explain how sudden environmental changes may initiate disease outbreaks and lead to critical declines in cultured or wild fish populations.}, 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={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={Journal of Fish DiseasesVolume 34, Issue 12 p. 921-925 Short Communication Clinical report: hyperplastic adipose lids in mackerel scad, Decapterus macarellus (Cuvier) S M Boylan, S M Boylan South Carolina Aquarium, Charleston, SC, USASearch for more papers by this authorC A Harms, C A Harms North Carolina State University, Center for Marine Sciences and Technology, Morehead City, NC, USASearch for more papers by this authorT Waltzek, T Waltzek Department of Environmental and Global Health, College of Public Health and Health Professions, University of Florida, Gainesville, FL, USASearch for more papers by this authorJ M Law, J M Law College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USASearch for more papers by this authorM Garner, M Garner Northwest ZooPath, Monroe, WA, USASearch for more papers by this authorJ Cassell, J Cassell South Carolina Aquarium, Charleston, SC, USASearch for more papers by this authorM H Fatzinger, M H Fatzinger North Carolina Aquarium at Fort Fisher, Kure Beach, NC, USASearch for more papers by this authorP Govett, P Govett Western University, College of Veterinary Medicine, Pomona, CA, USASearch for more papers by this author S M Boylan, S M Boylan South Carolina Aquarium, Charleston, SC, USASearch for more papers by this authorC A Harms, C A Harms North Carolina State University, Center for Marine Sciences and Technology, Morehead City, NC, USASearch for more papers by this authorT Waltzek, T Waltzek Department of Environmental and Global Health, College of Public Health and Health Professions, University of Florida, Gainesville, FL, USASearch for more papers by this authorJ M Law, J M Law College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USASearch for more papers by this authorM Garner, M Garner Northwest ZooPath, Monroe, WA, USASearch for more papers by this authorJ Cassell, J Cassell South Carolina Aquarium, Charleston, SC, USASearch for more papers by this authorM H Fatzinger, M H Fatzinger North Carolina Aquarium at Fort Fisher, Kure Beach, NC, USASearch for more papers by this authorP Govett, P Govett Western University, College of Veterinary Medicine, Pomona, CA, USASearch for more papers by this author First published: 13 October 2011 https://doi.org/10.1111/j.1365-2761.2011.01306.xCitations: 2 S M Boylan, South Carolina Aquarium, Charleston, SC, 29401, USA (e-mail:sboylan@scaquarium.org) Read the full textAboutPDF 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 Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume34, Issue12December 2011Pages 921-925 RelatedInformation}, 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={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={Myristoylated alanine-rich C-kinase substrate (MARCKS) is an actin binding protein substrate of protein kinase C (PKC) and critical for mouse and Xenopus development. Herein two MARCKS paralogs, marcksa and marcksb, are identified in zebrafish and the role of these genes in zebrafish development is evaluated. Morpholino-based targeting of either MARCKS protein resulted in increased mortality and a range of gross phenotypic abnormalities. Phenotypic abnormalities were classified as mild, moderate or severe, which is characterized by a slight curve of a full-length tail, a severe curve or twist of a full-length tail and a truncated tail, respectively. All three phenotypes displayed abnormal neural architecture. Histopathology of Marcks targeted embryos revealed abnormalities in retinal layering, gill formation and skeletal muscle morphology. These results demonstrate that Marcksa and Marcksb are required for normal zebrafish development and suggest that zebrafish are a suitable model to further study MARCKS function.}, 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={To determine whether clinically normal dogs have lesions in the pylorus and duodenum and to examine the expression of cyclooxygenase (COX) isoforms in the pylorus and duodenum of these dogs.27 clinically normal dogs.Physical examination was performed on clinically normal dogs from animal shelters and research projects; the dogs were then euthanized. After the dogs were euthanized, the pylorus and duodenum were photographed and scored for gross appearance of lesions. Samples were obtained for histologic evaluation and determination of COX expression via western blot analyses. Tissues from the pylorus and duodenum were categorized as normal, inflamed, or eroded on the basis of histologic analysis. Each histologic category of tissue was then evaluated to determine the correlation with gross appearance and COX expression.Of the 27 dogs, 5 had unremarkable histologic findings in the pylorus and duodenum. Inflammation was found in the pylorus of 10 dogs and in the duodenum of 5 dogs. Epithelial erosion was detected in the pylorus of 1 dog and in the duodenum of 3 dogs. Gross appearance was not significantly correlated with histologic appearance. Expression of COX-1 was not upregulated by inflammation, whereas COX-2 expression was increased by inflammation or erosion.Dogs that appear to be clinically normal may have underlying gastroduodenal lesions associated with upregulation of COX-2. Because of the inability to determine this during routine physical examination, practitioners should be aware of this potential situation when prescribing COX inhibitors.}, 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 The Buffalo River area of concern (AOC) was assigned an impaired status for the fish tumors and other deformities beneficial use impairment category by the New York State Department of Environmental Protection in 1989. This was initially based on an inadequately documented brown bullhead ( Ameiurus nebulosus ) feeding study using river sediment extracts. The presence of liver tumors was subsequently supported by reports of a 19 to 27% prevalence in wild brown bullhead between 1983 and 1988 and a 4.8% prevalence in 1998. However, neither fish size (or age) nor sample locations were given, and histopathological definitions were inconsistent in these previous studies. Therefore, in 2008, we re‐evaluated the prevalence of hepatocellular and chloangiocellular tumors (as well as other gross indicators of fish health) in brown bullhead averaging 25 cm in length collected from three reaches of the Buffalo River and recorded our collection sites by global positioning system. Among the 37 fish of appropriate size collected, only three exhibited liver tumors (8%). The tumors were evenly distributed within the three reaches, and only hepatocellular tumors were found. There were no differences in the prevalence of hepatic foci of alteration, body weight, length, or hepatosomatic index among the three reaches, but the conditions factor was significantly lower in fish from reach 2. Natural attenuation of water and sediment quality are the most likely causes for the decrease in liver tumors. The prevalence of liver tumors between 1998 and 2008 in the Buffalo River is similar to that found in recovery‐stage AOCs and some Great Lakes reference areas. Environ. Toxicol. Chem. 2010; 29:1748–1754. © 2010 SETAC}, 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 Objective —To determine whether Scyphomedusa jellyfish with eversion syndrome had alterations in husbandry conditions, elemental content, or histologic appearance, compared with unaffected jellyfish. Animals —123 jellyfish (44 with eversion syndrome and 79 without) at 6 institutions. Procedures —Elemental analyses were performed on 24 jellyfish with eversion syndrome and 49 without, and histologic examinations were performed on 20 jellyfish with eversion syndrome and 30 without. A questionnaire distributed to 39 institutions with Scyphomedusa jellyfish was used to gather information about husbandry, environmental conditions, and prevalence of eversion syndrome. Results —For the 39 institutions that responded to the questionnaire, prevalence of eversion syndrome ranged from 0% to 30%. For Aurelia aurita , eversion was more common at institutions with only captive-raised and no wild-caught jellyfish. Eversion was most common among young (approx 1- to 2-month-old) growing jellyfish and older (> 6-month-old) jellyfish. Elemental analysis revealed only minor differences between affected and unaffected jellyfish, with great variation among jellyfish from the same institution and among jellyfish from different institutions. Striated muscle degeneration and necrosis and extracellular matrix (mesoglea) degeneration were evident on histologic examination of affected jellyfish. Conclusions and Clinical Relevance —Results suggested that eversion syndrome is a complex phenomenon associated with degenerative changes of the bell matrix.}, 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 Objective —To assess cyclooxygenase (COX) expression and prostanoid concentrations in pyloric and duodenal mucosae of dogs after administration of nonsteroidal anti-inflammatory drugs (NSAIDs). Animals —8 healthy dogs. Procedures —Each dog received carprofen (4.4 mg/kg, q 24 h), deracoxib (2 mg/kg, q 24 h), aspirin (10 mg/kg, q 12 h), and placebo (1 dog treat, q 24 h) orally for 3 days (4-week interval between treatments). Before study commencement (baseline) and on day 3 of each treatment, pyloric and duodenal mucosal appearance was assessed endoscopically and biopsy specimens were obtained for histologic examination. Cyclooxygenase-1 and COX-2 protein expressions were assessed via western blotting, and prostanoid concentrations were measured via ELISAs. An ANOVA was used to analyze data. Results —Treatments had no effect on mucosal appearance and ulceration was not evident histologically. In pyloric and duodenal mucosae, COX-1 expression was unaffected by treatments. Cyclooxygenase-2 expression remained unchanged in pyloric mucosa; in duodenal mucosa, aspirin significantly increased COX-2 expression, compared with effects of deracoxib and carprofen. At baseline, total prostaglandin and thromboxane B 2 concentrations in pyloric mucosa were significantly greater than those in duodenal mucosa. Aspirin significantly decreased both prostanoid concentrations in both mucosal tissues, compared with other treatments. In pyloric mucosa, carprofen administration significantly decreased total prostaglandin and thromboxane B 2 concentrations, compared with deracoxib administration. Conclusions and Clinical Relevance —In dogs, prostanoid synthesis was greater in pyloric mucosa than it was in duodenal mucosa. Nonselective NSAIDs significantly decreased prostanoid concentrations in these mucosae, compared with the effects of a selective COX-2 NSAID.}, 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 Inadequate dissolved oxygen in the aquatic environment is a well-established cause of fish morbidity and mortality. The specific effects of hypoxia on immune function in fish, however, are not well characterized. In this study, the effects of acute hypoxia followed by reoxygenation (rapid tissue reperfusion) as a source of immunocompromise in Nile tilapia Oreochromis niloticus were investigated. Using a precision apparatus developed in our laboratory for hypoxia exposures, a series of assays of increasing specificity for immune function were performed on acutely hypoxia-stressed Nile tilapia: tier I consisted of histopathology, tier II of hematology, plasma chemistry, and determining cortisol concentration, and tier III of determining the phagocytic index and analyzing the expression of the cytokines transforming growth factor-β (TGF-β) and interleukin-1β (IL-1β). Nile tilapia were exposed to 7% oxygen saturation for 96 h, then tank water was rapidly reoxygenated. Sampling intervals were 48 and 96 h during hypoxia and 12 and 84 h during reperfusion. Histopathology showed no remarkable microscopic abnormalities in lymphoid or other tissues. Lymphopenia and neutrophilia were observed in peripheral blood. Plasma total protein, partial pressure of oxygen, and oxygen saturation were decreased in response to hypoxia. Plasma lipase decreased in response to hypoxia but returned to normal during reperfusion. Phagocytic capability and the phagocytic index decreased during hypoxia and 12 h reperfusion, whereas these values were recovered by 84 h reperfusion. The TGF-β transcription continued to increase during the exposures, the greatest production being at 12 h reperfusion, whereas IL-1β transcription decreased in response to hypoxia and reperfusion. We conclude that acute hypoxia triggered an overall downregulation of the immune system in the test fish. This suggests a possible factor in the pathogenesis of disease outbreaks in fish in which repeated, sublethal bouts of environmentally induced hypoxia lead to increased disease susceptibility and individual mortalities rather than massive fish kills.}, 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 λ transgenic medaka was developed to fully characterize the toxic effects induced by exposure to a mixture of organic pollutants in sediments. Embryos of the λ 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 (0.3×, 1×, and 2×) of an organic extract (OE) of sediments from the Seine estuary. The 1× 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× 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={Abstract 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 (≤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-β (TGF-β) 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-β 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 gamma -tocopherol and total oxidant scavenging capacity (TOSC) and alpha -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 μg 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}, publisher={BRITISH VETERINARY ASSOC}, 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={A 4-year-old castrated male Irish Setter was referred to the North Carolina State University Veterinary Teaching Hospital (NCSU-VTH) for prostatomegaly and chronic progressive tenesmus of 8 months' duration.One week before presentation to the NCSU-VTH, stranguria and hematuria were noted in addition to tenesmus.Abdominal radiographs and abdominal ultrasonography before referral identified an enlarged prostate (8 by 8 by 15 cm) in the pelvic canal extending into the abdominal cavity.Multiple areas of spondylosis of the caudal thoracic and lumbar spine also were present.Medical therapy by the referring veterinarian consisted of prednisone and antibiotics, including amoxicillin a (20 mg/kg PO q12h) and enrofloxacin b (5 mg/kg PO q12h).No improvement was noted with this treatment.Because of episodes of stranguria, intermittent urinary catheterization was performed before referral.On presentation to the NCSU-VTH, the dog was lethargic and dehydrated and had a body score of 3/9. 1 Rectal temperature, heart rate, and respiratory rate were 101.8ЊF, 72 beats/min, and 40 breaths/min.A firm, nonpainful, 10by 10-cm mass was palpable in the caudal abdomen.The urinary bladder could not be palpated.On rectal examination, the prostate occupied 90% of the pelvic canal, compressing and displacing the colon dorsolaterally.Peripheral lymph nodes were within normal limits for size.An intermittent grade II/VI systolic left apical murmur was auscultated.The remainder of the physical examination was unremarkable.Abnormalities found on CBC, serum biochemistry, and urinalysis included mild hyperglobulinemia (4.6 g/dL; normal, 1.8-4.4g/dL) and high alkaline phosphatase (333 IU/ L; normal, 12-150 IU/L).Urinalysis results included urinespecific gravity (1.045), proteinuria (3ϩ), bilirubinuria (3ϩ), hematuria (Ͼ3ϩ), increased red blood cells (Ͼ500/ hpf), and occasional coarse granular casts in the sediment.Thoracic radiographs were within normal limits, and no evidence of pulmonary metastases was present.A marked normal sinus arrhythmia and wandering pacemaker were present on ECG.Cardiac ultrasound examination revealed left ventricular dilatation with a thickened anterior mitral}, 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={To determine whether infection with Tritrichomonas foetus causes diarrhea in specific-pathogen-free or Cryptosporidium coinfected cats.4 cats with subclinical cryptosporidiosis (group 1) and 4 specific-pathogen-free cats (group 2).Cats were infected orogastrically with an axenic culture of T. foetus isolated from a kitten with diarrhea. Direct microscopy and protozoal culture of feces, fecal character, serial colonic mucosal biopsy specimens, and response to treatment with nitazoxanide (NTZ; group 1) or prednisolone (groups 1 and 2) were assessed.Infection with T. foetus persisted in all cats for the entire 203-day study and resulted in diarrhea that resolved after 7 weeks. Group-1 cats had an earlier onset, more severe diarrhea, and increased number of trichomonads on direct fecal examination, compared with group-2 cats. Use of NTZ eliminated shedding of T. foetus and Cryptosporidium oocysts, but diarrhea consisting of trichomonad-containing feces recurred when treatment was discontinued. Prednisolone did not have an effect on infection with T. foetus but resulted in reappearance of Cryptosporidium oocysts in the feces of 2 of 4 cats. During necropsy, T. foetus was isolated from contents of the ileum, cecum, and colon. Tritrichomonas foetus organisms and antigen were detected on surface epithelia and within superficial detritus of the cecal and colonic mucosa.After experimental inoculation in cats, T. foetus organisms colonize the ileum, cecum, and colon, reside in close contact with the epithelium, and are associated with transient diarrhea that is exacerbated by coexisting cryptosporidiosis but not treatment with prednisolone.}, 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} }