@article{krane_shockley_malarkey_miller_miller_tokarz_jensen_janardhan_breen_mariani_2022, title={Inter-pathologist agreement on diagnosis, classification and grading of canine glioma}, volume={7}, ISSN={["1476-5829"]}, url={https://doi.org/10.1111/vco.12853}, DOI={10.1111/vco.12853}, abstractNote={Abstract}, journal={VETERINARY AND COMPARATIVE ONCOLOGY}, author={Krane, Gregory A. and Shockley, Keith R. and Malarkey, David E. and Miller, Andrew D. and Miller, C. Ryan and Tokarz, Debra A. and Jensen, Heather L. and Janardhan, Kyathanahalli S. and Breen, Matthew and Mariani, Christopher L.}, year={2022}, month={Jul} }
 @article{meurs_williams_deprospero_friedenberg_malarkey_ezzell_keene_adin_defrancesco_tou_2021, title={A deleterious mutation in the ALMS1 gene in a naturally occurring model of hypertrophic cardiomyopathy in the Sphynx cat}, volume={16}, ISSN={["1750-1172"]}, DOI={10.1186/s13023-021-01740-5}, abstractNote={Abstract}, number={1}, journal={ORPHANET JOURNAL OF RARE DISEASES}, author={Meurs, Kathryn M. and Williams, Brian G. and DeProspero, Dylan and Friedenberg, Steven G. and Malarkey, David E. and Ezzell, J. Ashley and Keene, Bruce W. and Adin, Darcy B. and DeFrancesco, Teresa C. and Tou, Sandra}, year={2021}, month={Feb} }
 @article{krane_carly a. o'dea_malarkey_miller_miller_tokarz_jensen_janardhan_shockley_flagler_et al._2021, title={Immunohistochemical evaluation of immune cell infiltration in canine gliomas}, volume={7}, ISSN={["1544-2217"]}, DOI={10.1177/03009858211023946}, abstractNote={Evasion of the immune response is an integral part of the pathogenesis of glioma. In humans, important mechanisms of immune evasion include recruitment of regulatory T cells (Tregs) and polarization of macrophages toward an M2 phenotype. Canine glioma has a robust immune cell infiltrate that has not been extensively characterized. The purpose of this study was to determine the distribution of immune cells infiltrating spontaneous intracranial canine gliomas. Seventy-three formalin-fixed, paraffin-embedded tumor samples were evaluated using immunohistochemistry for CD3, forkhead box 3 (FOXP3), CD20, Iba1, calprotectin (Mac387), CD163, and indoleamine 2,3-dioxygenase (IDO). Immune cell infiltration was present in all tumors. Low-grade and high-grade gliomas significantly differed in the numbers of FoxP3+ cells, Mac387+ cells, and CD163+ cells ( P = .006, .01, and .01, respectively). Considering all tumors, there was a significant increase in tumor area fraction of CD163 compared to Mac387 ( P < .0001), and this ratio was greater in high-grade tumors than in low-grade tumors ( P = .005). These data warrant further exploration into the roles of macrophage repolarization or Treg interference therapy in canine glioma.}, journal={VETERINARY PATHOLOGY}, author={Krane, Gregory A. and Carly A. O'Dea and Malarkey, David E. and Miller, Andrew D. and Miller, C. Ryan and Tokarz, Debra A. and Jensen, Heather L. and Janardhan, Kyathanahalli S. and Shockley, Keith R. and Flagler, Norris and et al.}, year={2021}, month={Jul} }
 @article{shiomitsu_johnson_malarkey_pruitt_thrall_2009, title={Expression of epidermal growth factor receptor and vascular endothelial growth factor in malignant canine epithelial nasal tumours}, volume={7}, ISSN={["1476-5829"]}, DOI={10.1111/j.1476-5829.2009.00178.x}, abstractNote={Epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) signalling pathways play a role in carcinogenesis. Inhibition of EGF receptor (EGFR) and of VEGF is effective in increasing the radiation responsiveness of neoplastic cells both in vitro and in human trials. In this study, immunohistochemical evaluation was employed to determine and characterize the potential protein expression levels and patterns of EGFR and VEGF in a variety of canine malignant epithelial nasal tumours. Of 24 malignant canine nasal tumours, 13 (54.2%) were positive for EGFR staining and 22 (91.7%) were positive for VEGF staining. The intensity and percentage of immunohistochemically positive neoplastic cells for EGFR varied. These findings indicate that EGFR and VEGF proteins were present in some malignant epithelial nasal tumours in the dogs, and therefore, it may be beneficial to treat canine patients with tumours that overexpress EGFR and VEGF with specific inhibitors in conjunction with radiation.}, number={2}, journal={VETERINARY AND COMPARATIVE ONCOLOGY}, author={Shiomitsu, K. and Johnson, C. L. and Malarkey, D. E. and Pruitt, A. F. and Thrall, D. E.}, year={2009}, month={Jun}, pages={106–114} }
 @article{mcmullen_clode_pandiri_malarkey_michau_gilger_2008, title={Epibulbar melanoma in a foal}, volume={11}, ISSN={1463-5216 1463-5224}, url={http://dx.doi.org/10.1111/j.1463-5224.2008.00637.x}, DOI={10.1111/j.1463-5224.2008.00637.x}, abstractNote={Abstract}, journal={Veterinary Ophthalmology}, publisher={Wiley}, author={McMullen, Richard J. and Clode, Alison B. and Pandiri, Arun Kumar R. and Malarkey, David E. and Michau, Tammy Miller and Gilger, Brian C.}, year={2008}, month={Sep}, pages={44–50} }
 @article{kleiter_malarkey_ruslander_thrall_2004, title={Expression of cyclooxygenase-2 in canine epithelial nasal tumors}, volume={45}, ISSN={["1058-8183"]}, DOI={10.1111/j.1740-8261.2004.04046.x}, abstractNote={Cyclooxygenase‐2 (COX‐2) is an enzyme upregulated in some human and animal tumors. Enzymatic products are associated with tumorigenic activities. Given the poor response of canine nasal tumors to radiation, we considered the possibility that some of this resistance may be associated with COX‐2 expression. To test this, 21 formalin‐fixed, paraffin‐embedded, and archived biopsy samples from canine epithelial nasal tumors were analyzed for COX‐2 expression using immunohistochemistry. The biopsies were collected from dogs prior to radiation therapy. COX‐2 expression was present in 17 of 21 (81%) tumors. The expression was observed in several different tumor types, including nasal carcinomas, adenocarcinomas, and squamous cell carcinomas. Samples from five control dogs without nasal neoplasia were also analyzed for COX‐2 staining. These specimens were characterized by varying degrees of lymphoplasmacytic rhinitis with scattered regions of COX‐2 positive respiratory epithelial and stromal cells. Whether the intensity and distribution of COX‐2 expression in nasal tumors can be used as a prognostic marker requires further investigation. A combination therapy of irradiation and a selective COX‐2 inhibitor appears worthy of clinical investigation in the treatment of canine epithelial nasal tumors.}, number={3}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Kleiter, M and Malarkey, DE and Ruslander, DE and Thrall, DE}, year={2004}, pages={255–260} }
 @article{williams_malarkey_cohn_patrick_dye_toews_2004, title={Identification of spontaneous feline idiopathic pulmonary fibrosis - Morphology and ultrastructural evidence for a type II pneumocyte defect}, volume={125}, ISSN={["1931-3543"]}, DOI={10.1378/chest.125.6.2278}, abstractNote={STUDY OBJECTIVES
Idiopathic pulmonary fibrosis (IPF) is a poorly understood chronic respiratory disease of humans, which has no correlate in other animals. Understanding the role that inflammation, alveolar epithelial cells, and myofibroblasts play in the progression of the disease is controversial, and hampered by the lack of an animal model. We have identified spontaneous IPF in domestic cats and hypothesized that this newly identified disease shares the pathology of human IPF; further, this work provides data suggesting that the disease is related to a defect in type II pneumocyte biology.


SETTING AND SUBJECTS
Chronic respiratory disease with pathology consistent with usual interstitial pneumonia (UIP) spontaneously developed in 16 domestic cats.


RESULTS
The histopathology of feline IPF consisted of the following: (1) interstitial fibrosis with fibroblast/myofibroblast foci, (2) honeycombing with alveolar epithelial metaplasia and type II pneumocyte hyperplasia, and (3) alveolar interstitial smooth-muscle metaplasia. Interstitial inflammation was not a prominent feature of the disease. alpha-Smooth muscle actin-positive myofibroblasts were prominent in myofibroblast foci, beneath honeycomb and hyperplastic epithelium, and in alveolar septa away from the remodeling. Feline IPF type II pneumocyte ultrastructure is similar to a heritable form of human IPF, with abnormal cytoplasmic lamellar body-like inclusions.


CONCLUSIONS
We conclude the following: (1) chronic respiratory disease with clinical and pathology features of UIP/IPF occurs in the domestic cat; (2) as in human IPF, the type II pneumocyte and myofibroblasts are important cellular constituents of feline IPF; and (3) type II cell ultrastructure suggests feline IPF is a defect in the type II pneumocyte.}, number={6}, journal={CHEST}, author={Williams, K and Malarkey, D and Cohn, L and Patrick, D and Dye, J and Toews, G}, year={2004}, month={Jun}, pages={2278–2288} }
 @article{douglass_berry_thrall_malarkey_spaulding_2003, title={Radiographic features of aortic bulb/valve mineralization in 20 dogs}, volume={44}, ISSN={["1058-8183"]}, DOI={10.1111/j.1740-8261.2003.tb01443.x}, abstractNote={The radiographic features of aortic bulb/valve mineralization in 20 dogs were reviewed. Extent, shape, number, and location of mineralization were recorded. Five of the dogs had additional alternate imaging examinations, including bone scintigraphy, echocardiography, and thoracic computed tomography. A necropsy was done on one dog, and the area of mineralization was evaluated using routine histology. The median age was 10 (mean 9.7; SD ± 2.7) years. There were five males, seven neutered males, one female, and seven neutered females. The breeds were: Irish setter (6); rottweiler (7); chow‐chow (1); miniature dachshund (1); borzoi (1); English setter (1); English springer spaniel (1); great Dane (1); and greyhound (1). Dogs with both right and left lateral radiographs (n = 17) had mineralization visible on both views, more conspicuously on the right lateral radiograph (n = 12). Aortic bulb mineralization was identified on the ventrodorsal radiograph of only one dog. On lateral radiographs, the aortic bulb mineralization was localized within the 4th intercostal space and in the craniodorsal quadrant of the cardiac silhouette. In nine of the dogs, there were complex or multiple mineralizations and in 11 dogs, there was a single curvilinear mineral opacity oriented in a caudoventral to craniodorsal direction. In all radiographs, the mineralization was in the expected position of the aortic bulb, and echocardiography (n = 4), spiral computed tomography (n = 2), and necropsy (n = 1) confirmed that the mineralization was within the aortic bulb. Clinical pathologic data of the dogs suggested no reason for metastatic mineralization. Exact etiopathogenesis of the lesions were not determined in this study. Based on the histologic findings in one dog, the mineralization seen in the aortic root is similar to a form of dystrophic mineralization called Monckeberg's calcific arteriosclerosis in humans. No clinical signs attributable to the mineralization were observed.}, number={1}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Douglass, JP and Berry, CR and Thrall, DE and Malarkey, DE and Spaulding, KA}, year={2003}, pages={20–27} }
 @article{flowers_hammerberg_wood_malarkey_dam_levy_mclawhorn_2002, title={Heterobilharzia americana infection in a dog}, volume={220}, ISSN={["0003-1488"]}, DOI={10.2460/javma.2002.220.193}, abstractNote={A 7-year-old castrated male Golden Retriever cross was evaluated because of intermittent blood-tinged diarrhea, severe weight loss, anorexia, and lethargy of 2 months' duration; the dog was unresponsive to antimicrobial and standard anthelmintic treatment. Results of fecal flotations for parasite ova were negative. Alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase activities and total protein and globulin conentrations were greater than reference ranges. Biopsy specimens were obtained during laparotomy and examination revealed multiple granulomatous lesions with helminth ova nidi in the intestine, pancreas, liver, and mesenteric lymph node. Saline solution direct smear and saline solution sedimentation of feces yielded trematode ova that were morphologically consistent with Heterobilharzia americana. Identification was confirmed when miracidia were hatched from these ova and produced characteristic cercariae from infected snails. An antigen capture ELISA, typically used for the diagnosis of schistosomiasis in humans, was performed, and schistosome circulating anodic antigen was detected. Treatment with 30 mg of praziquantel/kg (14 mg/lb) of body weight stopped ova shedding, removed detectable circulating antigens, and caused the dog's body weight and attitude to return to normal. Although this is the first report of canine heterobilharziasis in North Carolina, it suggests that heterobilharziasis is underdiagnosed in dogs that have contact with water frequented by raccoons. Inappropriate diagnostic procedures can foil accurate detection of this parasitic disease.}, number={2}, journal={JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Flowers, JR and Hammerberg, B and Wood, SL and Malarkey, DE and Dam, GJ and Levy, MG and McLawhorn, LD}, year={2002}, month={Jan}, pages={193–196} }
 @article{chernoff_hunter_hall_rosen_brownie_malarkey_marr_herkovits_2002, title={Lack of teratogenicity of microcystin-LR in the mouse and toad}, volume={22}, ISSN={["0260-437X"]}, DOI={10.1002/jat.800}, abstractNote={Abstract}, number={1}, journal={JOURNAL OF APPLIED TOXICOLOGY}, author={Chernoff, N and Hunter, ES and Hall, LL and Rosen, MB and Brownie, CF and Malarkey, D and Marr, M and Herkovits, J}, year={2002}, pages={13–17} }
 @article{nyska_moomaw_foley_maronpot_malarkey_cummings_peddada_moyer_allen_travlos_et al._2002, title={The hepatic endothelial carcinogen riddelliine induces endothelial apoptosis, mitosis, S phase, and p53 and hepatocytic vascular endothelial growth factor expression after short-term exposure}, volume={184}, ISSN={["1096-0333"]}, DOI={10.1006/taap.2002.9485}, abstractNote={Riddelliineis a naturally occurring pyrrolizidine alkaloid found in certain poisonous rangeland plants of the western United States. In National Toxicology Program 2-year studies, riddelliine induced high incidences of hemangiosarcoma in the liver of F344/N rats (both sexes) and B6C3F1 mice (males). To understand this pathogenesis, we tested short-term effects of riddelliine. Three groups (control; 1.0 mg/kg/day, high dose used in the 2-year study; and 2.5 mg/kg/day) of seven male F344/N rats per group were terminated after 8 consecutive doses and 30 doses (6 weeks, excluding weekends). Serum vascular endothelial growth factor (VEGF), histological, immunohistochemical [factor VIII-related antigen/von Willebrand factor (fVIII-ra/vWf)], VEGF, VEGF receptor-2 (VEGFR2), glutathione S-transferase-pi, S-phase (BrdU), p53, apoptosis, and ultrastructural evaluations were performed on the liver. Following 8 doses of 1.0 and 2.5 mg/kg/day, increased numbers of apoptotic and S-phase nuclei appeared in hepatocytes and endothelial cells. Following 30 doses of 1.0 and 2.5 mg/kg/day, hepatocytes exhibited reduced mitosis, fewer S-phase nuclei, increased hypertrophy, and fatty degeneration, while endothelial cells showed karyomegaly, cytomegaly, decreased apoptosis, more S-phase nuclei, and p53 positivity. Hepatocytes of treated animals expressed higher VEGF immunopositivity. That altered endothelial cells were fVIII-ra/vWf and VEGFR2 positive confirmed their identity. These changes may have promoted hemangiosarcoma development upon long-term exposure through endothelial adduct formation, apoptosis, proliferation of endothelial cells having undamaged and/or damaged DNA, and mutation. Endothelial proliferation may also have been promoted through endothelial arrest at S phase, which was associated with endothelial karyo- and cytomegaly, resulting in hepatocytic hypoxia, triggering VEGF induction.}, number={3}, journal={TOXICOLOGY AND APPLIED PHARMACOLOGY}, author={Nyska, A and Moomaw, CR and Foley, JF and Maronpot, RR and Malarkey, DE and Cummings, CA and Peddada, S and Moyer, CF and Allen, DG and Travlos, G and et al.}, year={2002}, month={Nov}, pages={153–164} }
 @article{baty_malarkey_atkins_defrancesco_sidley_keene_2001, title={Natural history of hypertrophic cardiomyopathy and aortic thromboembolism in a family of domestic shorthair cats}, volume={15}, ISSN={["0891-6640"]}, DOI={10.1892/0891-6640(2001)015<0595:NHOHCA>2.3.CO;2}, abstractNote={A feline domestic shorthair queen and her 3 offspring were all diagnosed with asymptomatic hypertrophic cardiomyopathy (HCM). The family has been followed for 13 years, and 3 cats have died of aortic thromboembolism (ATE). This communication documents the long-term progression of HCM in these cats that presented with mild left ventricular hypertrophy and hyperdynamic systolic ventricular function, developed progressive left atrial enlargement, and eventually resulted in hypodynamic left ventricular systolic function with relative left ventricular chamber dilation at the time of ATE.}, number={6}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Baty, CJ and Malarkey, DE and Atkins, CE and DeFrancesco, TC and Sidley, J and Keene, BW}, year={2001}, pages={595–599} }
 @article{colitz_malarkey_dykstra_mcgahan_davidson_2000, title={Histologic and immunohistochemical characterization of lens capsular plaques in dogs with cataracts}, volume={61}, ISSN={["0002-9645"]}, DOI={10.2460/ajvr.2000.61.139}, abstractNote={Abstract}, number={2}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Colitz, CMH and Malarkey, D and Dykstra, MJ and McGahan, MC and Davidson, MG}, year={2000}, month={Feb}, pages={139–143} }
 @article{colitz_malarkey_woychik_wilkinson_2000, title={Persistent hyperplastic tunica vasculosa lentis and persistent hyperplastic primary vitreous in transgenic line TgN3261Rpw}, volume={37}, ISSN={["0300-9858"]}, DOI={10.1354/vp.37-5-422}, abstractNote={ Persistent hyperplastic tunica vasculosa lentis and persistent hyperplastic primary vitreous are congenital ocular anomalies that can lead to cataract formation. A line of insertional mutant mice, TgN3261Rpw, generated at the Oak Ridge National Laboratory in a large-scale insertional mutagenesis program was found to have a low incidence (8/243; 3.29%) of multiple developmental ocular abnormalities. The ocular abnormalities include persistent hyperplastic primary vitreous, persistent hyperplastic tunica vasculosa lentis, failure of cleavage of the anterior segment, retrolental fibrovascular membrane, posterior polar cataract, and detached retina. This transgenic mouse line provides an ontogenetic model because of the high degree of similarity of this entity in humans, dogs, and mice. }, number={5}, journal={VETERINARY PATHOLOGY}, author={Colitz, CMH and Malarkey, DE and Woychik, RP and Wilkinson, JE}, year={2000}, month={Sep}, pages={422–427} }
 @article{christensen_romach_healy_gonzales_anderson_malarkey_corton_fox_cattley_goldsworthy_1999, title={Altered bcl-2 family expression during non-genotoxic hepatocarcinogenesis in mice}, volume={20}, ISSN={["1460-2180"]}, DOI={10.1093/carcin/20.8.1583}, abstractNote={Dysregulation of apoptosis is an important component of multistage hepatocarcinogenesis. Members of the bcl-2 protein family are important in the regulation of apoptosis and their expression is altered in several cancers. The objectives of the present study were to determine whether the expression of members of the bcl-2 protein family are altered in mouse liver during acute treatment with non-genotoxic carcinogens and throughout non-genotoxic hepatocarcinogenesis. Acute treatment of B6C3F1 mice with phenobarbital resulted in increased levels of bcl-2 and decreased levels of bax protein, while acute treatment with WY-14,643 resulted in increased bcl-2 and BAG-1 protein in the liver. Following chronic treatment, altered hepatic foci and adenomas were classified as: small-cell, heterogeneous basophilic lesions (spontaneous or tetrachlorodibenzo-p-dioxin-induced); large-cell, homogeneous basophilic lesions (WY-14,643-induced); acidophilic lesions (phenobarbital- or chlordane-induced). Of the small-cell heterogeneous basophilic lesions, 86% of foci (31/36) and 85% of adenomas (35/41) exhibited increased bcl-2 protein levels compared with surrounding normal hepatocytes, whereas only 12.5% of foci (4/36) and 12% of adenomas (5/41) exhibited increased bcl-X(L) levels. Of the large-cell, homogenous, basophilic lesions, 100% of foci (3/3) and 90% of adenomas (9/10) expressed bcl-2 protein, whereas 100% of foci (3/3) and 80% of adenomas (8/10) exhibited increased bcl-X(L) protein levels compared with surrounding normal hepatocytes. Of the acidophilic lesions, the majority of foci (28/32, 88%) and adenomas (47/50, 94%) expressed increased bcl-X(L), whereas increased bcl-2 was observed in only 12.5% of acidophilic preneoplastic foci (4/32) and 14% of acidophilic adenomas (7/50). Of the carcinomas analyzed, 81% expressed increased bcl-2 (54/67), 78% expressed increased bcl-X(L) (52/67) and 69% expressed increased levels of both bcl-2 and bcl-X(L) (46/67). Collectively, only 8% of preneoplastic foci, 3% of adenomas and 1.5% of carcinomas did not express either bcl-2 or bcl-X(L). These results suggest that regulation of apoptotic proteins is altered during non-genotoxic carcinogenesis in mouse liver. Furthermore, there were both chemical- and lesion-specific aspects of expression of apoptotic proteins during hepatocarcinogenesis in mice.}, number={8}, journal={CARCINOGENESIS}, author={Christensen, JG and Romach, EH and Healy, LN and Gonzales, AJ and Anderson, SP and Malarkey, DE and Corton, JC and Fox, TR and Cattley, RC and Goldsworthy, TL}, year={1999}, month={Aug}, pages={1583–1590} }
 @article{trempus_ward_farris_malarkey_faircloth_cannon_mahler_1998, title={Association of v-Ha-ras transgene expression with development of erythroleukemia in Tg.AC transgenic mice}, volume={153}, ISSN={["0002-9440"]}, DOI={10.1016/S0002-9440(10)65565-4}, abstractNote={A transgenic mouse line (Tg.AC) carrying an activated v-Ha-ras oncogene fused to the embryonic zeta-globin promoter develops an array of spontaneous epithelial and mesenchymal neoplasms. In this report we describe the morphological, immunophenotypic, and molecular features of a unique hematopoietic neoplasm in these mice. The cardinal lesion of this disease is marked hepatomegaly due to leukemic proliferation and infiltration. In the peripheral blood, there is a marked increase in the number of metarubricytes and other less differentiated erythroid progenitor cells. Leukemic cells stain positively with an erythroid-associated nuclear transcription factor (GATA-1). Using a reverse transcription polymerase chain reaction assay, co-expression of GATA-1 and endogenous zeta-globin genes is detected in hematopoietic tissues of nonleukemic transgenic and nontransgenic mice. ras transgene expression is, however, detected only in normal bone marrow and leukemic tissues of transgenic mice, and 5' mapping experiments using S1 protection analysis of total RNA from leukemic tissue indicates that transcription of the transgene mRNA is initiated from the natural zeta-globin promoter start site, supporting the belief that the zeta-globin promoter directs v-Ha-ras expression in erythroid progenitor cells, ultimately leading to leukemic transformation.}, number={1}, journal={AMERICAN JOURNAL OF PATHOLOGY}, author={Trempus, CS and Ward, S and Farris, G and Malarkey, D and Faircloth, RS and Cannon, RE and Mahler, JF}, year={1998}, month={Jul}, pages={247–254} }
 @article{hansen_malarkey_wilkinson_rosenberg_woychik_tennant_1998, title={Effect of the viable-yellow (A(vy)) agouti allele on skin tumorigenesis and humoral hypercalcemia in v-Ha-ras transgenic TG.AC mice}, volume={19}, ISSN={["0143-3334"]}, DOI={10.1093/carcin/19.10.1837}, abstractNote={We previously reported that papillomas can arise from the follicular epithelium of v-Ha-ras transgenic TGxAC mice. Since the viable-yellow mutation (A(vy)) of the mouse agouti gene which regulates coat color pigmentation by acting within the micro-environment of the hair follicle has been shown to function as a tumor promoter in the liver, we hypothesized that it may also play a role in TGxAC skin tumorigenesis. Endogenous agouti protein product was detected in the outer root sheath of anagen hair follicles following plucking of the hair shaft, but not in the interfollicular epithelium, in TGxAC mice on an FVB/N genetic background. It was also detected in papillomas from these mice produced by 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment or plucking. Expression of the A(vy) allele in the v-Ha-ras transgenic TGxAC mouse line results in an approximately 2-fold increase in papilloma development compared with controls which did not carry the A(vy) allele following twice-weekly treatment with 1.25, 2.5 or 5.0 microg TPA. In addition, TPA-treated, papilloma-bearing F1 mice which carried the A(vy) allele, but not F1 mice which did not carry the A(vy) allele, exhibited a syndrome of humoral hypercalcemia mediated by parathyroid hormone-related protein (PTHrP) that led to weight loss, hypercalcemia and hypophosphatemia. Thus, we conclude that the A(vy) allele can influence the development of skin tumors and PTHrP-mediated humoral hypercalcemia in v-Ha-ras transgenic TGxAC mice.}, number={10}, journal={CARCINOGENESIS}, author={Hansen, LA and Malarkey, DE and Wilkinson, JE and Rosenberg, M and Woychik, RE and Tennant, RW}, year={1998}, month={Oct}, pages={1837–1845} }
 @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{mahler_flagler_malarkey_mann_haseman_eastin_1998, title={Spontaneous and chemically induced proliferative lesions in Tg.AC transgenic and p53-heterozygous mice}, volume={26}, ISSN={["0192-6233"]}, DOI={10.1177/019262339802600406}, abstractNote={ Recently, the use of selected genetically altered mouse models in the detection of carcinogens after short-term chemical exposures has been evaluated. Studies of several chemicals conducted by the National Toxicology Program in Tg.AC transgenic and heterozygous p53-deficient mice have been completed recently and represent a major contribution to this effort, as well as the largest accumulation to date of toxicologic pathology data in these 2 lines of mice. The purpose of this report is to describe the proliferative target organ effects observed in this set of studies, as well as to present the tumor profile in the control groups of this data set. These findings provide a comprehensive toxicologic assessment of these 2 genetically altered mouse strains, which are of emerging importance in toxicologic pathology. }, number={4}, journal={TOXICOLOGIC PATHOLOGY}, author={Mahler, JF and Flagler, ND and Malarkey, DE and Mann, PC and Haseman, JK and Eastin, W}, year={1998}, pages={501–511} }
 @article{malarkey_ton_hailey_devereux_1997, title={A PCR-RFLP method for the detection of Helicobacter hepaticus in frozen or fixed liver from B6C3F(1) mice}, volume={25}, ISSN={["0192-6233"]}, DOI={10.1177/019262339702500611}, abstractNote={ Establishing the diagnosis of Helicobacter hepaticus infection in mouse liver has recently become important for the interpretation of rodent carcinogenicity bioassays. A seminested primer polymerase chain reaction (PCR) amplification of the bacterial 16S ribosomal RNA gene in combination with a restriction fragment length polymorphism (RFLP) assay was designed to identify and distinguish H. hepaticus from H. muridarum and H. bilis in mouse liver. The PCR-RFLP assay was applied to formalin-fixed, paraffin-embedded and, when available, corresponding frozen liver tissues from male and female B6C3F, mice with or without histologic evidence of infection from various National Toxicology Program 2-yr bioassay studies. PCR products consistent with H. hepaticus were detected in 10-80% of livers from mice in studies with other evidence of infection that were frozen or fixed for less than 24 hr but not in liver fixed for several weeks. The sensitivity of the PCR-RFLP assay for H. hepaticus on formalin-fixed, paraffin-embedded mouse liver varied between studies from markedly decreased when compared to the results from frozen liver or histologic evaluation to nearly equivalent or more sensitive than histologic evaluation. The PCR-RFLP results appeared dependent on the duration of fixation and bacterial load but not on the presence of hepatitis, sampling from neoplastic or nonneoplastic liver, or sex of the mouse. }, number={6}, journal={TOXICOLOGIC PATHOLOGY}, author={Malarkey, DE and Ton, TV and Hailey, JR and Devereux, TR}, year={1997}, pages={606–612} }