@misc{cullen_miller_2006, title={The role of pathology in the identification of drug-induced hepatic toxicity}, volume={2}, ISSN={["1744-7607"]}, DOI={10.1517/17425255.2.2.241}, abstractNote={Pathologists play a central role in the recognition and prevention of drug-induced toxicity. Pathologists engaged in clinical practice must identify a pattern of histological lesions that are interpreted in concert with a variety of clinical data to determine the probability of drug-induced toxicity versus background disease processes and the most likely drug, often of many, to have caused the specific injury. Toxicological pathologists, working in concert with other scientists, have the responsibility of preventing drug-induced toxicity in humans by identifying potentially toxic drugs and keeping them from the marketplace. In this process of drug development, a broad array of invivo testing using a number of animal species and invitro assays are used. Technological advances require pathologists to integrate molecular-based mechanistic data effectively with traditional morphological evaluation to develop a more detailed grasp of the pathogenesis of drug-induced injury. All pathologists have the responsibility to effectively and accurately communicate their findings and interpretations to the appropriate audiences.}, number={2}, journal={EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY}, author={Cullen, John M. and Miller, Richard T.}, year={2006}, month={Apr}, pages={241–247} }
 @article{dalton_miller_meyer_2003, title={The  herbicide metolachlor induces liver cytochrome P450s 2B1/2 and 3A1/2, but not thyroxine-uridine dinucleotide phosphate glucuronosyltransferase and associated thyroid gland activity}, volume={22}, DOI={10.1080/10915810390220063}, number={4}, journal={International Journal of Toxicology}, author={Dalton, S. R. and Miller, R. T. and Meyer, S. A.}, year={2003}, pages={287–295} }
 @article{miller_scappino_ling_corton_2001, title={Role of thyroid hormones in hepatic effects of peroxisome proliferators}, volume={29}, ISSN={["0192-6233"]}, DOI={10.1080/019262301301418964}, abstractNote={ Peroxisome proliferators are endocrine disrupting chemicals that cause liver tumors in rodents but not humans. Although the receptor that mediates key hepatic effects, the peroxisome proliferator-activated receptor alpha (PPAR-α), and its endogenous ligands have been identified, the mechanism whereby these commonly used chemicals cause liver tumors in rodents has yet to be elucidated. Species differences in PPAR-α and DNA response elements may explain some of the variability in response upon exposure to peroxisome proliferators. The possibility that thyroid-modulating effects of peroxisome proliferators may contribute to the hepatic effects of peroxisome proliferators has yet to be fully explored. When the potent peroxisome proliferator, WY-14,643, was given to hypothyroid rats, there was a blunting of the hepatomegaly and hepatocyte proliferative responses seen in thyroid-intact animals. Acyl-CoA oxidase activity was unaltered by changes in thyroid hormone status. In addition, preliminary evidence indicates that peroxisome proliferators increased hepatic thyroid receptor (TRα1) expression, but TRα1 levels in liver tumors were similar to those in unexposed animals. Significant differences between humans and rodents with respect to thyroid hormone physiology and metabolism, in conjunction with the results of these studies, may be indicative of yet another mechanism to explain differential sensitivity to hepatic effects of peroxisome proliferators. }, number={1}, journal={TOXICOLOGIC PATHOLOGY}, author={Miller, RT and Scappino, LA and Ling, SM and Corton, JC}, year={2001}, pages={149–155} }
 @article{miller_anderson_corton_cattley_2000, title={Apoptosis, mitosis and cyclophilin-40 expression in regressing peroxisome proliferator-induced adenomas}, volume={21}, ISSN={["0143-3334"]}, DOI={10.1093/carcin/21.4.647}, abstractNote={Chronic exposure to peroxisome proliferators (PP), including certain industrial and pharmaceutical chemicals, causes liver cancer in rodents. Continuous exposure to PP is needed for tumor development since the frequency of hepatocellular neoplasms is decreased in animals returned to control diet. To determine cellular and molecular events responsible for enhanced growth in PP-induced liver tumors, we evaluated the relationships of WY-14,643 levels, apoptosis, mitosis and cyclophilin-40 (Cyp-40) expression in regressing tumors induced by WY-14,643, a potent PP. Male F344 rats were fed WY-14,643 (0.1%) in the diet for 43 weeks and then switched to control diet for 2, 3, 5 or 36 days. Mean serum and hepatic concentrations of WY-14,643 were decreased as early as 2 days following removal of WY-14,643 as compared with rats continuously fed WY-14,643. Adenomas from rats maintained on WY-14,643 markedly compressed surrounding parenchyma. Evidence of adenoma regression was observed by 3 days of WY-14,643 withdrawal and was characterized by loss of compression. Decreased compression corresponded to increases in the apoptotic index and decreases in the mitotic index in regressing adenomas at 2, 3, and 5 days following the switch to control diet. Cyclophilins are multifunctional receptor proteins involved in numerous signal transduction pathways, including those mediated by cyclosporin, a liver tumor promoter in rats. Cyp-40 expression was markedly increased in adenomas from continuously exposed rats, but expression returned to levels similar to surrounding parenchyma in adenomas after 5 days of WY-14,643 withdrawal. Taken together, these results indicate that WY-14, 643-induced adenomas regress rapidly following withdrawal of the PP in association with declining liver WY-14,643 levels, suggesting that peroxisome proliferator-activated receptor alpha may mediate PP-induced alterations in mitogenic and/or apoptotic regulation in growing tumors, in conjunction with alterations in Cyp-40 signal transduction.}, number={4}, journal={CARCINOGENESIS}, author={Miller, RT and Anderson, SP and Corton, JC and Cattley, RC}, year={2000}, month={Apr}, pages={647–652} }
 @article{dorman_struve_vitarella_byerly_goetz_miller_2000, title={Neurotoxicity of manganese chloride in neonatal and adult CD rats following subchronic (21-day) high-dose oral exposure}, volume={20}, DOI={10.1002/(SICI)1099-1263(200005/06)20:3<179::AID-JAT631>3.0.CO;2-C}, abstractNote={The purpose of this study was to evaluate the relative sensitivity of neonatal and adult CD rats to manganese‐induced neurotoxicity. Identical oral manganese chloride (MnCl2) doses (0, 25, or 50 mg kg−1 body wt. day−1) were given to neonatal rats throughout lactation (i.e. from postnatal day (PND) 1 through 21) and to adult male rats for 21 consecutive days. The MnCl2 doses administered to neonates were ca. 100‐fold higher than those resulting from the consumption of an equivalent volume of rat's milk. Rats were assessed using similar behavioral and neurochemical evaluations. Several statistically significant changes occurred in Mn‐exposed rats relative to control animals. Neonates given the high dose of MnCl2 had reduced body weight gain. An increased pulse‐elicited acoustic startle response amplitude was observed in neonates from both MnCl2 treatment groups on PND 21. Increased striatal, hippocampal, hindbrain and cortical Mn concentrations were observed in all Mn‐exposed neonates on PND 21. Increased hypothalamic and cerebellar Mn concentrations were also observed on PND 21 in neonates from the high‐dose group only. Increased striatal, cerebellar and brain residue Mn concentrations were observed in adult rats from the high‐dose group. Increased striatal dopamine and 3,4‐dihydroxyphenylacetic acid levels were observed only in PND 21 neonates from the high‐dose group. No treatment‐related changes were observed in clinical signs, motor activity (assessed in neonates on PND 13, 17, 21 ± 1 and in adults), passive avoidance (assessed in neonates on PND 20 ± 1 and in adults) or neuropathology (assessed in PND 21 neonates only). The results of our experiment suggest that neonates may be at greater risk for Mn‐induced neurotoxicity when compared to adults receiving similar high oral levels of Mn. Copyright © 2000 John Wiley & Sons, Ltd.}, number={3}, journal={Journal of Applied Toxicology}, author={Dorman, D. C. and Struve, M. F. and Vitarella, D. and Byerly, F. L. and Goetz, J. and Miller, R.}, year={2000}, pages={179–187} }
 @article{corton_swanson_miller_cattley_1999, title={Alteration of protein kinase C isoform-specific expression during rat hepatocarcinogenesis after exposure to the peroxisome proliferator WY-14,643}, volume={137}, ISSN={["0304-3835"]}, DOI={10.1016/S0304-3835(98)00334-6}, abstractNote={The role of protein kinase C (PKC) isoforms in mediating peroxisome proliferator chemical- (PPC) induced hepatocarcinogenesis was examined. After an acute gavage exposure to WY-14,643 (WY) membrane-bound PKCdelta and cytosolic PKCbeta decreased, whereas the expression of the other isoforms was not altered. After a 13-week chronic exposure, membrane-bound PKCbeta, delta and zeta levels decreased. In WY-induced hepatocellular adenomas, PKCalpha was increased, and PKCbeta was further decreased in membrane fractions. These results, taken together with previous studies, indicate that alterations in PKCalpha, beta and delta isoforms, which regulate mitogenesis, could play important roles in perpetuating the high cell proliferative rate in PPC-induced hepatocellular adenomas.}, number={1}, journal={CANCER LETTERS}, author={Corton, JC and Swanson, C and Miller, RT and Cattley, RC}, year={1999}, month={Mar}, pages={9–15} }
 @article{russell_perkins_hoffman_miller_walker_fuller_sellon_1999, title={Platelets from thrombocytopenic ponies acutely infected with equine infectious anemia virus are activated in vivo and hypofunctional}, volume={259}, ISSN={["0042-6822"]}, DOI={10.1006/viro.1999.9737}, abstractNote={Thrombocytopenia is a consistent finding and one of the earliest hematological abnormalities in horses acutely infected with equine infectious anemia virus (EIAV), a lentivirus closely related to human immunodeficiency virus. Multifactorial mechanisms, including immune-mediated platelet destruction and impaired platelet production, are implicated in the pathogenesis of EIAV-associated thrombocytopenia. This study was undertaken to investigate whether regenerative thrombopoiesis and platelet destruction occurred in ponies acutely infected with EIAV. Circulating large, immature platelets were increased in ponies acutely infected with EIAV late in the infection when platelet count was at a nadir. Morphometric analysis of bone marrow from acutely infected ponies revealed significant increased in megakaryocyte area and megakaryocyte nuclear area. A trend toward increased numbers of megakaryocytes was also observed. Platelets from acutely infected ponies had increased surface-bound fibrinogen and ultrastructural changes consistent with in vivo platelet activation. Platelets also had hypofunctional aggregation responses to three agonists in vitro. We conclude that thrombocytopenia in ponies acutely infected with EIAV is regenerative and suggest that bone marrow platelet production is not severely compromised in these ponies. Our findings reveal that in vivo platelet activation occurs in ponies acutely infected with EIAV, and as a result platelets are hypofunctional in vitro. Activation of platelets in vivo may cause platelet degranulation or formation of platelet aggregates, which would result in removal of these damages platelets from circulation. This may represent a form of nonimmune-mediated platelet destruction in ponies acutely infected with EIAV.}, number={1}, journal={VIROLOGY}, author={Russell, KE and Perkins, PC and Hoffman, MR and Miller, RT and Walker, KM and Fuller, FJ and Sellon, DC}, year={1999}, month={Jun}, pages={7–19} }
 @article{powers_merrill_degernes_miller_latimer_barnes_1998, title={Axillary cystadenocarcinoma in a Moluccan cockatoo (Cacatua moluccensis)}, volume={42}, ISSN={["0005-2086"]}, DOI={10.2307/1592495}, abstractNote={An adult Moluccan cockatoo (Cacatua moluccensis) was diagnosed with a cystadenocarcinoma in the right axillary region that was treated symptomatically with surgical debulking and periodic drainage. The bird eventually died and a necropsy was performed. The neoplasm extended through the humerus, and small neoplastic foci were seen within the ipsilateral lung parenchyma. Rare groupings of microvilli were observed lining intercellular canalicular lumens on electron microscopy within the axillary tumor. These findings suggest a respiratory neoplasm, although the tissue of origin remained undetermined.}, number={2}, journal={AVIAN DISEASES}, author={Powers, LV and Merrill, CL and Degernes, LA and Miller, R and Latimer, KS and Barnes, HJ}, year={1998}, pages={408–412} }
 @article{gerard_healy_bowman_miller_1998, title={Cutaneous lymphoma with extensive periarticular involvement in a horse}, volume={213}, number={3}, journal={Journal of the American Veterinary Medical Association}, author={Gerard, M. P. and Healy, L. N. and Bowman, K. F. and Miller, R. T.}, year={1998}, pages={391–393} }
 @article{russell_walker_miller_sellon_1998, title={Hyperglobulinemia and lymphocyte subset changes in naturally infected, in apparent carriers of equine infectious anemia virus}, volume={59}, number={8}, journal={American Journal of Veterinary Research}, author={Russell, K. E. and Walker, K. M. and Miller, R. T. and Sellon, D. C.}, year={1998}, pages={1009–1015} }
 @article{hailey_haseman_bucher_radovsky_malarkey_miller_nyska_maronpot_1998, title={Impact of Helicobacter hepaticus infection in B6C3F(1) mice from twelve national toxicology program two-year carcinogenesis studies}, volume={26}, ISSN={["0192-6233"]}, DOI={10.1177/019262339802600503}, abstractNote={ Male and female B6C3F1 mice from 12 National Toxicology Program (NTP) 2-yr carcinogenesis studies were found to be infected with Helicobacter hepaticus. Many of the male mice from 9 of these studies had an associated hepatitis (affected studies). Helicobacter hepaticus has been reported to be associated with an increased incidence of hepatitis and hepatocellular neoplasms in the A/JCr male mouse. We attempted to determine if the data from the Helicobacter-affected NTP B6C3F1 mouse studies were compromised and unsuitable for cancer hazard identification. The incidences of neoplasms of the liver (both hepatocellular and hemangiosarcoma) but not of other organs in control male B6C3F1 mice were increased in affected studies as compared with control males from unaffected studies. The increased incidence of hepatocellular neoplasms was observed in those males exhibiting H. hepaficus-associated hepatitis. Other observations further differentiated control male mice from affected and unaffected studies. H- ras codon 61 CAA to AAA mutations were less common in liver neoplasms from males from affected studies as compared with historical and study controls. In addition, increases in cell proliferation rates and apoptosis were observed in the livers of male mice with H. hepaticus-associaled hepatitis. These data support the hypothesis that the increased incidence of liver neoplasms is associated with H. hepaticus and that hepatitis may be important in the pathogenesis. Therefore, interpretation of carcinogenic effects in the liver of B6C3F1 mice may be confounded if there is H. hepaticus-associaled hepatitis. }, number={5}, journal={TOXICOLOGIC PATHOLOGY}, author={Hailey, JR and Haseman, JK and Bucher, JR and Radovsky, AE and Malarkey, DE and Miller, RT and Nyska, A and Maronpot, RR}, year={1998}, pages={602–611} }
 @article{massat_miller_deyoung_schiller_aberman_deyoung_1998, title={Single-stage revision using an uncemented, porous-coated, anatomic endoprosthesis in two dogs: Case report}, volume={27}, ISSN={["1532-950X"]}, DOI={10.1111/j.1532-950X.1998.tb00125.x}, abstractNote={Objective—To describe the clinical and radiographic features of septic and aseptic failure of two femoral endoprostheses and their successful revision.}, number={3}, journal={VETERINARY SURGERY}, author={Massat, BJ and Miller, RT and DeYoung, BA and Schiller, RA and Aberman, HM and DeYoung, DJ}, year={1998}, pages={268–277} }
 @article{king_miller_1997, title={Fatal perforating intestinal ulceration attributable to flunixin meglumine overdose in rats}, volume={47}, number={2}, journal={Laboratory Animal Science}, author={King, C. S. and Miller, R. T.}, year={1997}, pages={205–208} }