@article{gookin_hartley_aicher_mathews_cullen_cullen_callahan_stowe_seiler_jacob_et al._2023, title={Gallbladder microbiota in healthy dogs and dogs with mucocele formation}, volume={18}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0281432}, abstractNote={To date studies have not investigated the culture-independent microbiome of bile from dogs, a species where aseptic collection of bile under ultrasound guidance is somewhat routine. Despite frequent collection of bile for culture-based diagnosis of bacterial cholecystitis, it is unknown whether bile from healthy dogs harbors uncultivable bacteria or a core microbiota. The answer to this question is critical to understanding the pathogenesis of biliary infection and as a baseline to exploration of other biliary diseases in dogs where uncultivable bacteria could play a pathogenic role. A pressing example of such a disease would be gallbladder mucocele formation in dogs. This prevalent and deadly condition is characterized by excessive secretion of abnormal mucus by the gallbladder epithelium that can eventually lead to rupture of the gallbladder or obstruction of bile flow. The cause of mucocele formation is unknown as is whether uncultivable, and therefore unrecognized, bacteria play any systematic role in pathogenesis. In this study we applied next-generation 16S rRNA gene sequencing to identify the culture-negative bacterial community of gallbladder bile from healthy dogs and gallbladder mucus from dogs with mucocele formation. Integral to our study was the use of 2 separate DNA isolations on each sample using different extraction methods and sequencing of negative control samples enabling recognition and curation of contaminating sequences. Microbiota findings were validated by simultaneous culture-based identification, cytological examination of bile, and fluorescence in-situ hybridization (FISH) performed on gallbladder mucosa. Using culture-dependent, cytological, FISH, and 16S rRNA sequencing approaches, results of our study do not support existence of a core microbiome in the bile of healthy dogs or gallbladder mucus from dogs with mucocele formation. Our findings further document how contaminating sequences can significantly contribute to the results of sequencing analysis when performed on samples with low bacterial biomass.}, number={2}, journal={PLOS ONE}, author={Gookin, Jody L. and Hartley, Ashley N. and Aicher, Kathleen M. and Mathews, Kyle G. and Cullen, Rachel and Cullen, John M. and Callahan, Benjamin J. and Stowe, Devorah M. and Seiler, Gabriela S. and Jacob, Megan E. and et al.}, year={2023}, month={Feb} }
 @article{schreeg_cullen_robertson_gookin_2023, title={Histologic characterization of the major duodenal papilla and association with concurrent biliary, pancreatic, and intestinal pathology in cats}, volume={8}, ISSN={["1544-2217"]}, DOI={10.1177/03009858231189450}, abstractNote={ Conjoining of the major pancreatic duct and common bile duct at the major duodenal papilla (MDP) is suspected to predispose cats to the clinical syndrome of “triaditis.” However, microanatomy of the MDP or presence of lesions at the MDP has not been assessed in cats with or without triaditis. The aims of this study were to characterize feline MDP histomorphology and to identify associations between MDP anatomy/disease and the presence of biliary, pancreatic, or intestinal inflammation or neoplasia. Histologic assessment was prospectively performed on the MDP, duodenum, jejunum, ileum, liver, and pancreas from 124 client-owned cats undergoing postmortem examination. The majority of cats (104/124, 84%) had a complex ductular network at the MDP, with no distinction between pancreatic and common bile ducts. Lymphoid aggregates at the MDP were common (63/124, 51%). Inflammation of the MDP (MDPitis) was present in 35 of 124 cats (28%) and was often concurrent with cholangitis, pancreatitis, or enteritis (32/35, 91%), but was only associated with enteritis (19/35, 54%, P < .05). Triaditis was less common (19/124, 15%), but was associated with both conjoined MDP anatomy (19/19, 100%, P < .05) and MDPitis (12/19, 63%, P < .05). Neoplasia was present in 37 of 124 cats (29%), with lymphoma (28/37, 78%) predominating. Enteropathy-associated T-cell lymphoma type 2 (EATL2) was most common ( n = 16/37, 43%) and was associated with triaditis and MDPitis ( P < .05). These findings suggest that anatomy, immune activation, and/or inflammation of the MDP may play a role in the pathogenesis of triaditis. Further studies are needed to elucidate the relationships between triaditis, MDPitis, and EATL2. }, journal={VETERINARY PATHOLOGY}, author={Schreeg, Megan E. and Cullen, John M. and Robertson, James and Gookin, Jody L.}, year={2023}, month={Aug} }
 @article{slead_callahan_schreeg_seiler_stowe_azcarate-peril_jacob_gookin_2023, title={Microbiome analysis of bile from apparently healthy cats and cats with suspected hepatobiliary disease}, volume={9}, ISSN={["1939-1676"]}, url={https://doi.org/10.1111/jvim.16852}, DOI={10.1111/jvim.16852}, abstractNote={Abstract}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Slead, Tanner S. and Callahan, Benjamin J. and Schreeg, Megan E. and Seiler, Gabriela S. and Stowe, Devorah M. and Azcarate-Peril, Maria Andrea and Jacob, Megan E. and Gookin, Jody L.}, year={2023}, month={Sep} }
 @article{gookin_strong_bruno-barcena_stauffer_williams_wassack_azcarate-peril_estrada_seguin_balzer_et al._2022, title={Randomized placebo-controlled trial of feline-origin Enterococcus hirae probiotic effects on preventative health and fecal microbiota composition of fostered shelter kittens}, volume={9}, ISSN={["2297-1769"]}, url={https://doi.org/10.3389/fvets.2022.923792}, DOI={10.3389/fvets.2022.923792}, abstractNote={IntroductionDiarrhea is the second most common cause of mortality in shelter kittens. Studies examining prevention strategies in this population are lacking. Probiotics are of particular interest but studies in cats are largely limited to healthy adults or those with induced disease. Only one study in domestic cats describes the use of host-derived bacteria as a probiotic. We previously identified Enterococcus hirae as a dominant species colonizing the small intestinal mucosa in healthy shelter kittens. Oral administration of a probiotic formulation of kitten-origin E. hirae (strain 1002-2) mitigated the increase in intestinal permeability and fecal water loss resulting from experimental enteropathogenic E. coli infection in purpose-bred kittens. Based on these findings, we hypothesized that administration of kitten-origin E. hirae to weaned fostered shelter kittens could provide a measurable preventative health benefit.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Gookin, Jody L. L. and Strong, Sandra J. J. and Bruno-Barcena, Jose M. and Stauffer, Stephen H. H. and Williams, Shelby and Wassack, Erica and Azcarate-Peril, M. Andrea and Estrada, Marko and Seguin, Alexis and Balzer, Joerg and et al.}, year={2022}, month={Nov} }
 @article{watson_hazen_rasko_jacob_elfenbein_stauffer_gookin_2021, title={Comparative Genomics of Atypical Enteropathogenic Escherichia coli from Kittens and Children Identifies Bacterial Factors Associated with Virulence in Kittens}, volume={89}, ISSN={["1098-5522"]}, DOI={10.1128/IAI.00619-20}, abstractNote={
            Typical enteropathogenic
            Escherichia coli
            (tEPEC) is a leading cause of diarrhea and associated death in children worldwide. Atypical EPEC (aEPEC) lacks the plasmid encoding bundle-forming pili and is considered less virulent, but the molecular mechanism of virulence is poorly understood.
          }, number={3}, journal={INFECTION AND IMMUNITY}, author={Watson, Victoria E. and Hazen, Tracy H. and Rasko, David A. and Jacob, Megan E. and Elfenbein, Johanna R. and Stauffer, Stephen H. and Gookin, Jody L.}, year={2021}, month={Mar} }
 @article{bierlein_hedgespeth_azcarate-peril_stauffer_gookin_2021, title={Dysbiosis of fecal microbiota in cats with naturally occurring and experimentally induced Tritrichomonas foetus infection}, volume={16}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0246957}, abstractNote={The protozoal pathogen Tritrichomonas foetus infects the colon of domestic cats and is a major cause of chronic colitis and diarrhea. Treatment failure is common, but antibiotics may improve clinical signs in a subset of cats, leading researchers to question involvement of the colonic microbiota in disease pathogenesis. Studies performed in women with venereal Trichomonas vaginalis infections have revealed that dysbiosis of host microbiota contributes to pathogenicity with similar findings also found in mice with intestinal Tritrichomonas musculis The aim of this study was to characterize differences in the fecal microbiota of cats with and without naturally occurring T. foetus infection and in a group of kittens prior to and after experimentally induced infection. Archived fecal DNA from cats undergoing testing for T. foetus infection (n = 89) and experimentally infected kittens (n = 4; at pre-, 2 weeks, and 9 weeks post-infection) were analyzed by sequencing of 16S rRNA genes. Amongst the naturally infected population, the genera Megamonas and Helicobacter were significantly increased in prevalence and abundance in cats testing positive for T. foetus infection. In the group of four experimentally infected kittens, fecal samples post-infection had significantly lower abundance of genus Dialister and Megamonas and greater abundance of the class Betaproteobacteria and family Succinivibrionaceae. We hypothesize that T. foetus promotes dysbiosis by competition for fermentable substrates used by these bacteria and that metabolic byproducts may contribute to the pathogenesis of colonic inflammation and diarrhea. Future studies are warranted for the measurement of fecal concentrations of microbial and protozoal metabolites in cats with T. foetus infection for the identification of potential therapeutic targets.}, number={2}, journal={PLOS ONE}, author={Bierlein, Metzere and Hedgespeth, Barry A. and Azcarate-Peril, M. Andrea and Stauffer, Stephen H. and Gookin, Jody L.}, year={2021}, month={Feb} }
 @article{lindaberry_vaden_aicher_seiler_robertson_cianciolo_yang_gookin_2021, title={Proteinuria in dogs with gallbladder mucocele formation: A retrospective case control study}, volume={35}, ISSN={["1939-1676"]}, DOI={10.1111/jvim.16051}, abstractNote={Abstract}, number={2}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Lindaberry, Crystal and Vaden, Shelly and Aicher, Kathleen M. and Seiler, Gabriela and Robertson, James and Cianciolo, Rachel and Yang, Ching and Gookin, Jody L.}, year={2021}, month={Mar}, pages={878–886} }
 @article{hedgespeth_stauffer_robertson_gookin_2020, title={Association of fecal sample collection technique and treatment history with Tritrichomonas foetus polymerase chain reaction test results in 1717 cats}, volume={34}, ISSN={["1939-1676"]}, url={http://dx.doi.org/10.1111/jvim.15727}, DOI={10.1111/jvim.15727}, abstractNote={Abstract}, number={2}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Hedgespeth, Barry A. and Stauffer, Stephen H. and Robertson, James B. and Gookin, Jody L.}, year={2020}, month={Mar}, pages={734–741} }
 @article{birkenheuer_royal_cerreta_hemstreet_lunn_gookin_mcgarvey_2020, title={Perceptions and attitudes of Small Animal Internal Medicine specialists toward the publication requirement for board certification}, volume={34}, ISSN={["1939-1676"]}, DOI={10.1111/jvim.15717}, abstractNote={Abstract}, number={2}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Birkenheuer, Adam J. and Royal, Kenneth D. and Cerreta, Anthony and Hemstreet, Daniel and Lunn, Katharine F. and Gookin, Jody L. and McGarvey, Stephanie}, year={2020}, month={Mar}, pages={574–580} }
 @article{watson_jacob_bruno-bárcena_amirsultan_stauffer_píqueras_frias_gookin_2019, title={Influence of the intestinal microbiota on disease susceptibility in kittens with experimentally-induced carriage of atypical enteropathogenic Escherichia coli}, volume={231}, ISSN={0378-1135}, url={http://dx.doi.org/10.1016/j.vetmic.2019.03.020}, DOI={10.1016/j.vetmic.2019.03.020}, abstractNote={Typical enteropathogenic E. coli (tEPEC) carries the highest hazard of death in children with diarrhea and atypical EPEC (aEPEC) was recently identified as significantly associated with diarrheal mortality in kittens. In both children and kittens there is a significant association between aEPEC burden and diarrheal disease, however the infection can be found in individuals with and without diarrhea. It remains unclear to what extent, under what conditions, or by what mechanisms aEPEC serves as a primary pathogen in individuals with diarrhea. It seems likely that a combination of host and bacterial factors enable aEPEC to cause disease in some individuals and not in others. The purpose of this study was to determine the impact of aEPEC on intestinal function and diarrhea in kittens following experimentally-induced carriage and the influence of a disrupted intestinal microbiota on disease susceptibility. Results of this study identify aEPEC as a potential pathogen in kittens. In the absence of disruption to the intestinal microbiota, kittens are resistant to clinical signs of aEPEC carriage but demonstrate significant occult changes in intestinal absorption and permeability. Antibiotic-induced disruption of the intestinal microbiota prior to infection increases subsequent intestinal water loss as determined by % fecal wet weight. Enrichment of the intestinal microbiota with a commensal member of the feline mucosa-associated microbiota, Enterococcus hirae, ameliorated the effects of aEPEC experimental infection on intestinal function and water loss. These observations begin to unravel the mechanisms by which aEPEC infection may be able to exploit susceptible hosts.}, journal={Veterinary Microbiology}, publisher={Elsevier BV}, author={Watson, Victoria E. and Jacob, Megan E. and Bruno-Bárcena, José M. and Amirsultan, Sophia and Stauffer, Stephen H. and Píqueras, Victoria O. and Frias, Rafael and Gookin, Jody L.}, year={2019}, month={Apr}, pages={197–206} }
 @article{ferguson_foster_sherry_magness_nielsen_gookin_2019, title={Interferon-λ3 Promotes Epithelial Defense and Barrier Function Against Cryptosporidium parvum Infection}, volume={8}, ISSN={2352-345X}, url={http://dx.doi.org/10.1016/j.jcmgh.2019.02.007}, DOI={10.1016/j.jcmgh.2019.02.007}, abstractNote={Background & AimsThe epithelial response is critical for intestinal defense against Cryptosporidium, but is poorly understood. To uncover the host strategy for defense against Cryptosporidium, we examined the transcriptional response of intestinal epithelial cells (IECs) to C parvum in experimentally infected piglets by microarray. Up-regulated genes were dominated by targets of interferon (IFN) and IFN-λ3 was up-regulated significantly in infected piglet mucosa. Although IFN-λ has been described as a mediator of epithelial defense against viral pathogens, there is limited knowledge of any role against nonviral pathogens. Accordingly, the aim of the study was to determine the significance of IFN-λ3 to epithelial defense and barrier function during C parvum infection.MethodsThe significance of C parvum–induced IFN-λ3 expression was determined using an immunoneutralization approach in neonatal C57BL/6 mice. The ability of the intestinal epithelium to up-regulate IFN-λ2/3 expression in response to C parvum infection and the influence of IFN-λ2/3 on epithelial defense against C parvum invasion, intracellular development, and loss of barrier function was examined using polarized monolayers of a nontransformed porcine-derived small intestinal epithelial cell line (IPEC-J2). Specifically, changes in barrier function were quantified by measurement of transepithelial electrical resistance and transepithelial flux studies.ResultsImmunoneutralization of IFN-λ2/3 in C parvum–infected neonatal mice resulted in a significantly increased parasite burden, fecal shedding, and villus blunting with crypt hyperplasia during peak infection. In vitro, C parvum was sufficient to induce autonomous IFN-λ3 and interferon-stimulated gene 15 expression by IECs. Priming of IECs with recombinant human IFN-λ3 promoted cellular defense against C parvum infection and abrogated C parvum–induced loss of barrier function by decreasing paracellular permeability to sodium.ConclusionsThese studies identify IFN-λ3 as a key epithelial defense mechanism against C parvum infection. The epithelial response is critical for intestinal defense against Cryptosporidium, but is poorly understood. To uncover the host strategy for defense against Cryptosporidium, we examined the transcriptional response of intestinal epithelial cells (IECs) to C parvum in experimentally infected piglets by microarray. Up-regulated genes were dominated by targets of interferon (IFN) and IFN-λ3 was up-regulated significantly in infected piglet mucosa. Although IFN-λ has been described as a mediator of epithelial defense against viral pathogens, there is limited knowledge of any role against nonviral pathogens. Accordingly, the aim of the study was to determine the significance of IFN-λ3 to epithelial defense and barrier function during C parvum infection. The significance of C parvum–induced IFN-λ3 expression was determined using an immunoneutralization approach in neonatal C57BL/6 mice. The ability of the intestinal epithelium to up-regulate IFN-λ2/3 expression in response to C parvum infection and the influence of IFN-λ2/3 on epithelial defense against C parvum invasion, intracellular development, and loss of barrier function was examined using polarized monolayers of a nontransformed porcine-derived small intestinal epithelial cell line (IPEC-J2). Specifically, changes in barrier function were quantified by measurement of transepithelial electrical resistance and transepithelial flux studies. Immunoneutralization of IFN-λ2/3 in C parvum–infected neonatal mice resulted in a significantly increased parasite burden, fecal shedding, and villus blunting with crypt hyperplasia during peak infection. In vitro, C parvum was sufficient to induce autonomous IFN-λ3 and interferon-stimulated gene 15 expression by IECs. Priming of IECs with recombinant human IFN-λ3 promoted cellular defense against C parvum infection and abrogated C parvum–induced loss of barrier function by decreasing paracellular permeability to sodium. These studies identify IFN-λ3 as a key epithelial defense mechanism against C parvum infection.}, number={1}, journal={Cellular and Molecular Gastroenterology and Hepatology}, publisher={Elsevier BV}, author={Ferguson, Sylvia H. and Foster, Derek M. and Sherry, Barbara and Magness, Scott T. and Nielsen, Dahlia M. and Gookin, Jody L.}, year={2019}, pages={1–20} }
 @article{strong_gookin_correa_banks_2019, title={Interventions and observations associated with survival of orphaned shelter kittens undergoing treatment for diarrhea}, volume={3}, ISSN={1098-612X 1532-2750}, url={http://dx.doi.org/10.1177/1098612X19840459}, DOI={10.1177/1098612X19840459}, abstractNote={Objectives The objective of this study was to identify significant associations between treatment interventions and survival of orphaned shelter kittens with diarrhea. }, journal={Journal of Feline Medicine and Surgery}, publisher={SAGE Publications}, author={Strong, Sandra Jo and Gookin, Jody Lynn and Correa, Maria Teresa and Banks, Ron Eugene}, year={2019}, month={Mar}, pages={1098612X1984045} }
 @article{aicher_cullen_seiler_lunn_mathews_gookin_2019, title={Investigation of adrenal and thyroid gland dysfunction in dogs with ultrasonographic diagnosis of gallbladder mucocele formation}, volume={14}, ISSN={1932-6203}, url={http://dx.doi.org/10.1371/journal.pone.0212638}, DOI={10.1371/journal.pone.0212638}, abstractNote={Gallbladder mucocele formation is an emerging disease in dogs characterized by increased secretion of condensed granules of gel-forming mucin by the gallbladder epithelium and formation of an abnormally thick mucus that can culminate in obstruction of the bile duct or rupture of the gallbladder. The disease is associated with a high morbidity and mortality and its pathogenesis is unknown. Affected dogs have a significantly increased likelihood of concurrent diagnosis of hyperadrenocorticism, hypothyroidism, and hyperlipidemia. Whether these endocrinopathies represent coincidental primary disease processes that exacerbate gallbladder mucocele formation in predisposed dogs or reflect a concurrent disruption of endocrine and lipid metabolism is unclear. In this study, we investigated a hypothesis that dogs with gallbladder mucocele formation would have a high prevalence of occult and atypical abnormalities in adrenal cortical and thyroid gland function that would suggest the presence of endocrine disruption and provide deeper insight into disease pathogenesis. We performed a case-control study of dogs with and without ultrasonographic diagnosis of gallbladder mucocele formation and profiled adrenal cortical function using a quantitative mass spectrometry-based assay of serum adrenal-origin steroids before and after administration of synthetic cosyntropin. We simultaneously profiled serum thyroid hormone concentrations and evaluated iodine sufficiency by measurement of urine iodine:creatinine ratios (UICR). The studies were complemented by histological examination of archival thyroid tissue and measurements of thyroid gland organic iodine from dogs with gallbladder mucocele formation and control dogs. Dogs with gallbladder mucocele formation demonstrated an exaggerated cortisol response to adrenal stimulation with cosyntropin. A prevalence of 10% of dogs with gallbladder mucocele formation met laboratory-based criteria for suspect or definitive diagnosis of hyperadrenocorticism. A significantly greater number of dogs with gallbladder mucocele formation had basal serum dehydroepiandrosterone (DHEAS) increases compared to control dogs. A high percentage of dogs with gallbladder mucocele formation (26%) met laboratory-based criteria for diagnosis of hypothyroidism, but lacked detection of anti-thyroglobulin antibodies. Dogs with gallbladder mucocele formation had significantly higher UICRs than control dogs. Examination of thyroid tissue from an unrelated group of dogs with gallbladder mucocele formation did not demonstrate histological evidence of thyroiditis or significant differences in content of organic iodine. These findings suggest that dogs with gallbladder mucocele formation have a greater capacity for cortisol synthesis and pinpoint DHEAS elevations as a potential clue to the underlying pathogenesis of the disease. A high prevalence of thyroid dysfunction with absent evidence for autoimmune thyroiditis suggest a disrupted thyroid hormone metabolism in dogs with gallbladder mucocele formation although an influence of non-thyroidal illness cannot be excluded. High UICR in dogs with gallbladder mucocele formation is of undetermined significance, but of interest for further study.}, number={2}, journal={PLOS ONE}, publisher={Public Library of Science (PLoS)}, author={Aicher, Kathleen M. and Cullen, John M. and Seiler, Gabriela S. and Lunn, Katharine F. and Mathews, Kyle G. and Gookin, Jody L.}, editor={Loor, Juan J.Editor}, year={2019}, month={Feb}, pages={e0212638} }
 @article{dickson_vose_bemis_daves_cecere_gookin_steiner_tolbert_2019, title={The effect of enterococci on feline Tritrichomonas foetus infection in vitro}, volume={273}, ISSN={["1873-2550"]}, DOI={10.1016/j.vetpar.2019.08.012}, abstractNote={Tritrichomonas foetus is a common cause of large bowel diarrhea in cats. Probiotics have been suggested to be effective for many intestinal pathogens; however, there are a lack of studies evaluating the effect of probiotics in T. foetus infection. In vitro studies were performed to evaluate the effect of a probiotic containing Enterococcus faecium (Efm) SF68 and a novel probiotic, Enterococcus hirae, on the inhibition of T. foetus growth, adhesion to, and cytotoxicity towards the intestinal epithelium. The effect of enterococci on T. foetus proliferation during co-culture was evaluated throughout log phase T. foetus growth. The previously validated in vitro co-culture model system using porcine intestinal epithelial cells (IPEC-J2) was used to evaluate the effect of enterococci on T. foetus adhesion and cytotoxicity towards intestinal epithelial cells. Cytotoxicity was assessed using fluorescent microscopy and spectrophotometry. Interactions of T. foetus, enterococci, and intestinal epithelial cells were assessed using scanning electron microscopy and immunofluorescence assays (IFA). Enterococcus-induced inhibition of T. foetus growth was demonstrated at concentrations as low as 104 enterococci colony forming units (CFU)/mL and was dependent, in part, on environmental pH and the presence of viable enterococci organisms. T. foetus adhesion, including with a ronidazole-resistant strain, was reduced with pretreatment of intestinal epithelial cells with enterococci but was not significantly affected when enterococci were introduced simultaneously or following T. foetus infection. Compared to Efm, E. hirae more effectively decreased T. foetus adhesion, suggesting its superior potential as a novel probiotic for T. foetus infection. There was no effect of enterococci treatment on T. foetus-induced intestinal epithelial cell cytotoxicity. Our results support further study into the investigation of a possible benefit of enterococci-containing probiotic treatment for prevention of T. foetus infection in at-risk uninfected cats.}, journal={VETERINARY PARASITOLOGY}, author={Dickson, Rachel and Vose, Julie and Bemis, David and Daves, Maggie and Cecere, Thomas and Gookin, Jody L. and Steiner, Joerg and Tolbert, M. Katherine}, year={2019}, month={Sep}, pages={90–96} }
 @inbook{davis_gookin_2018, place={Hoboken, NJ}, edition={10th}, title={Antiprotozoal Drugs}, booktitle={Veterinary Pharmacology and Therapeutics}, publisher={Wiley Blackwell Publishing}, author={Davis, JL and Gookin, JL}, editor={Riviere, J.E. and Papich, M.G.Editors}, year={2018}, pages={1128–1165} }
 @inbook{gookin_seiler_mathews_cullen_2018, edition={16th}, title={Canine Biliary Mucocele}, booktitle={Current Veterinary Therapy XVI}, publisher={W.B. Saunder’s Co. Philadelphia}, author={Gookin, J.L. and Seiler, G. and Mathews, K.G. and Cullen, J.}, editor={Bonagura, JD and Twedt, DEditors}, year={2018} }
 @inbook{gookin_lappin_2018, place={Philadelphia}, edition={16th}, title={Protozoal Gastrointestinal Disease}, booktitle={Current Veterinary Therapy XVI}, publisher={W.B. Saunder’s Co.}, author={Gookin, JL and Lappin, ME}, editor={Bonagura, JD and Twedt, DEditors}, year={2018} }
 @article{gookin_mathews_cullen_seiler_2018, title={Qualitative metabolomics profiling of serum and bile from dogs with gallbladder mucocele formation}, volume={13}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0191076}, abstractNote={Mucocele formation is characterized by secretion of abnormally thick mucus by the gallbladder epithelium of dogs that may cause obstruction of the bile duct or rupture of the gallbladder. The disease is increasingly recognized and is associated with a high morbidity and mortality. The cause of gallbladder mucocele formation in dogs is unknown. There is a strong breed predisposition and affected dogs have a high incidence of concurrent endocrinopathy or hyperlipidemia. These observations suggest a significant influence of both genetic and metabolic factors on disease pathogenesis. In this study, we investigated a theory that mucocele formation is associated with a syndrome of metabolic disruption. We surmised that a global, untargeted metabolomics approach could provide unique insight into the systemic pathogenesis of gallbladder mucocele formation and identify specific compounds as candidate biomarkers or treatment targets. Moreover, concurrent examination of the serum and hepatic duct bile metabolome would enable the construction of mechanism-based theories or identification of specific compounds responsible for altered function of the gallbladder epithelium. Abnormalities observed in dogs with gallbladder mucocele formation, including a 33-fold decrease in serum adenosine 5’-monophosphate (AMP), lower quantities of precursors required for synthesis of energy transporting nucleotides, and increases in citric acid cycle intermediates, suggest excess metabolic energy and a carbon surplus. Altered quantities of compounds involved in protein translation and RNA turnover, together with accumulation of gamma-glutamylated and N-acetylated amino acids in serum suggest abnormal regulation of protein and amino acid metabolism. Increases in lathosterol and 7α-hydroxycholesterol suggest a primary increase in cholesterol synthesis and diversion to bile acid formation. A number of specific biomarker compounds were identified for their ability to distinguish between control dogs and those that formed a gallbladder mucocele. Particularly noteworthy was a significant decrease in quantity of biologically active compounds that stimulate biliary ductal fluid secretion including adenosine, cAMP, taurolithocholic acid, and taurocholic acid. These findings support the presence of significant metabolic disruption in dogs with mucocele formation. A targeted, quantitative analysis of the identified serum biomarkers is warranted to determine their utility for diagnosis of this disease. Finally, repletion of compounds whose biological activity normally promotes biliary ductal secretion should be examined for any therapeutic impact for resolution or prevention of mucocele formation.}, number={1}, journal={PLOS ONE}, author={Gookin, Jody L. and Mathews, Kyle G. and Cullen, John and Seiler, Gabriela}, year={2018}, month={Jan} }
 @inbook{gookin_2018, place={Zaragoza}, title={Trichomonosis}, booktitle={Textbook of Clinical Parasitology in Dogs and Cats}, publisher={Grupo Asís Biomedia}, author={Gookin, J.L.}, editor={Beugnet, F and Halos, L and Guillot, JEditors}, year={2018} }
 @article{policelli smith_gookin_smolski_di cicco_correa_seiler_2017, title={Association between Gallbladder Ultrasound Findings and Bacterial Culture of Bile in 70 Cats and 202 Dogs}, volume={31}, ISSN={0891-6640}, url={http://dx.doi.org/10.1111/jvim.14792}, DOI={10.1111/jvim.14792}, abstractNote={BackgroundBacterial cholecystitis often is diagnosed by combination of gallbladder ultrasound (US) findings and positive results of bile culture. The value of gallbladder US in determining the likelihood of bile bacterial infection in cats and dogs with suspected biliary disease is unknown.}, number={5}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Policelli Smith, R. and Gookin, J.L. and Smolski, W. and Di Cicco, M.F. and Correa, M. and Seiler, G.S.}, year={2017}, month={Jul}, pages={1451–1458} }
 @article{watson_jacob_flowers_strong_debroy_gookin_2017, title={Association of Atypical Enteropathogenic Escherichia coli with Diarrhea and Related Mortality in Kittens}, volume={55}, ISSN={0095-1137 1098-660X}, url={http://dx.doi.org/10.1128/JCM.00403-17}, DOI={10.1128/jcm.00403-17}, abstractNote={ABSTRACT}, number={9}, journal={Journal of Clinical Microbiology}, publisher={American Society for Microbiology}, author={Watson, Victoria E. and Jacob, Megan E. and Flowers, James R. and Strong, Sandra J. and DebRoy, Chitrita and Gookin, Jody L.}, editor={Fenwick, BradEditor}, year={2017}, month={Jun}, pages={2719–2735} }
 @misc{gookin_hanrahan_levy_2017, title={The conundrum of feline trichomonosis: The more we learn the "trickier' it gets}, volume={19}, ISSN={["1532-2750"]}, DOI={10.1177/1098612x17693499}, abstractNote={Practical relevance: Trichomonosis of the large intestine of the cat was described as a cause of chronic diarrhea over 20 years ago. The trichomonad was identified as Tritrichomonas foetus, with a genotype that is distinct from venereal T foetus of cattle. }, number={3}, journal={JOURNAL OF FELINE MEDICINE AND SURGERY}, author={Gookin, Jody L. and Hanrahan, Katherine and Levy, Michael G.}, year={2017}, month={Mar}, pages={261–274} }
 @article{winston_piperisova_neel_gookin_2016, title={Cyniclomyces guttulatus Infection in Dogs: 19 Cases (2006-2013)}, volume={52}, ISSN={["1547-3317"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84957805483&partnerID=MN8TOARS}, DOI={10.5326/jaaha-ms-6307}, number={1}, journal={JOURNAL OF THE AMERICAN ANIMAL HOSPITAL ASSOCIATION}, author={Winston, Jenessa Andrzejewski and Piperisova, Ida and Neel, Jennifer and Gookin, Jody L.}, year={2016}, pages={42–51} }
 @article{fujishiro_scorza_gookin_lappin_2016, title={Evaluation of associations among Coxiella burnetii and reproductive abnormalities in cats}, volume={18}, ISSN={["1532-2750"]}, DOI={10.1177/1098612x15584693}, abstractNote={Objectives Coxiella burnetii is an obligate intracellular bacterium that is found worldwide, is associated or suggested to be associated with reproductive abnormalities in a number of species including cats, and is the cause of Q fever in humans. In a previous study, C burnetii DNA was amplified from the uterine tissues of 8.5% of client-owned cats in the USA but reproductive history was unknown and histopathological examination was not performed. In this study, uterine tissues of 26 normal cats and 11 cats with histopathological evidence of uterine disease or other reproductive abnormalities were evaluated for the presence of C burnetii. }, number={4}, journal={JOURNAL OF FELINE MEDICINE AND SURGERY}, author={Fujishiro, Madeline A. and Scorza, Andrea V. and Gookin, Jody L. and Lappin, Michael R.}, year={2016}, month={Apr}, pages={344–347} }
 @article{manning_birkenheuer_briley_montgomery_harris_vanone_gookin_2016, title={Intermittent At-Home Suctioning of Esophageal Content for Prevention of Recurrent Aspiration Pneumonia in 4 Dogs with Megaesophagus}, volume={30}, ISSN={["1939-1676"]}, DOI={10.1111/jvim.14527}, abstractNote={BackgroundMegaesophagus carries a poor to guarded prognosis due to death from aspiration pneumonia. Options for medical management of regurgitation are limited to strategic oral or gastrostomy tube feeding.}, number={5}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Manning, K. and Birkenheuer, A. J. and Briley, J. and Montgomery, S. A. and Harris, J. and Vanone, S. L. and Gookin, J. L.}, year={2016}, pages={1715–1719} }
 @article{tolbert_gookin_2016, title={Mechanisms of Tritrichomonas foetus Pathogenicity in Cats with Insights from Venereal Trichomonosis}, volume={30}, ISSN={0891-6640}, url={http://dx.doi.org/10.1111/jvim.13920}, DOI={10.1111/jvim.13920}, abstractNote={Almost 20 years has passed since trichomonosis was first recognized as a potential cause of diarrhea in domestic cats. Despite progress in confirming disease causation, developing means for diagnosis, and identifying approaches to treatment of the infection, we still know very little about how this parasite causes diarrhea. With increasing recognition of resistance of trichomonosis to treatment with 5‐nitroimidazole drugs, new treatment strategies based on an understanding of disease pathogenesis are needed. In this review, lessons learned from the pathogenesis of venereal trichomonosis in people and cattle are applied to clinical observations of trichomonosis in cats in effort to generate insight into areas where further research may be beneficial.}, number={2}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Tolbert, M.K. and Gookin, J.L.}, year={2016}, month={Mar}, pages={516–526} }
 @article{gookin_correa_peters_malueg_mathews_cullen_seiler_2015, title={Association of Gallbladder Mucocele Histologic Diagnosis with Selected Drug Use in Dogs: A Matched Case-Control Study}, volume={29}, ISSN={["1939-1676"]}, DOI={10.1111/jvim.13649}, abstractNote={BackgroundThe cause of gallbladder mucocele (GBM) formation in dogs currently is unknown. Many available drugs represent a newer generation of xenobiotics that may predispose dogs to GBM formation.}, number={6}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Gookin, J. L. and Correa, M. T. and Peters, A. and Malueg, A. and Mathews, K. G. and Cullen, J. and Seiler, G.}, year={2015}, pages={1464–1472} }
 @article{kesimer_cullen_cao_radicioni_mathews_seiler_gookin_2015, title={Excess Secretion of Gel-Forming Mucins and Associated Innate Defense Proteins with Defective Mucin Un-Packaging Underpin Gallbladder Mucocele Formation in Dogs}, volume={10}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0138988}, abstractNote={Mucosal protection of the gallbladder is vital yet we know very little about the mechanisms involved. In domestic dogs, an emergent syndrome referred to as gallbladder mucocele formation is characterized by excessive secretion of abnormal mucus that results in obstruction and rupture of the gallbladder. The cause of gallbladder mucocele formation is unknown. In these first mechanistic studies of this disease, we investigated normal and mucocele-forming dog gallbladders to determine the source, identity, biophysical properties, and protein associates of the culprit mucins with aim to identify causes for abnormal mucus behavior. We established that mucocele formation involves an adoptive excess secretion of gel forming mucins with abnormal properties by the gallbladder epithelium. The mucus is characterized by a disproportionally significant increase in Muc5ac relative to Muc5b, defective mucin un-packaging, and mucin-interacting innate defense proteins that are capable of dramatically altering the physical and functional properties of mucus. These findings provide an explanation for abnormal mucus behavior and based on similarity to mucus observed in the airways of people with cystic fibrosis, suggest that abnormal mechanisms for maintenance of gallbladder epithelial hydration may be an instigating factor for mucocele formation in dogs.}, number={9}, journal={PLOS ONE}, author={Kesimer, Mehmet and Cullen, John and Cao, Rui and Radicioni, Giorgia and Mathews, Kyle G. and Seiler, Gabriela and Gookin, Jody L.}, year={2015}, month={Sep} }
 @article{vandersea_birkenheuer_litaker_vaden_renschler_gookin_2015, title={Identification of Parabodo caudatus (class Kinetoplastea) in urine voided from a dog with hematuria}, volume={27}, ISSN={["1943-4936"]}, DOI={10.1177/1040638714562827}, abstractNote={A voided urine sample, obtained from a 13-year-old intact male dog residing in a laboratory animal research facility, was observed to contain biflagellate protozoa 5 days following an episode of gross hematuria. The protozoa were identified as belonging to the class Kinetoplastea on the basis of light microscopic observation of Wright–Giemsa-stained urine sediment in which the kinetoplast was observed basal to 2 anterior flagella. A polymerase chain reaction (PCR) assay using primers corresponding with conserved regions within the 18S ribosomal RNA gene of representative kinetoplastid species identified nucleotide sequences with 100% identity to Parabodo caudatus. Parabodo caudatus organisms were unable to be demonstrated cytologically or by means of PCR in samples collected from the dog’s environment. The dog had a history of 50 complete urinalyses performed over the 12-year period preceding detection of P. caudatus, and none of these were noted to contain protozoa. Moreover, the gross hematuria that was documented 5 days prior to detection of P. caudatus had never before been observed in this dog. Over the ensuing 2.5 years of the dog’s life, 16 additional complete urinalyses were performed, none of which revealed the presence of protozoa. Bodonids are commonly found in soil as well as in freshwater and marine environments. However, P. caudatus, in particular, has a 150-year-long, interesting, and largely unresolved history in people as either an inhabitant or contaminant of urine. This historical conundrum is revisited in the current description of P. caudatus as recovered from the urine of a dog.}, number={1}, journal={JOURNAL OF VETERINARY DIAGNOSTIC INVESTIGATION}, author={Vandersea, Mark W. and Birkenheuer, Adam J. and Litaker, R. Wayne and Vaden, Shelly L. and Renschler, Janelle S. and Gookin, Jody L.}, year={2015}, month={Jan}, pages={117–120} }
 @article{schneider_ames_dicicco_savage_atkins_wood_gookin_2015, title={Recovery of normal esophageal function in a kitten with diffuse megaesophagus and an occult lower esophageal stricture}, volume={17}, ISSN={["1532-2750"]}, DOI={10.1177/1098612x14542451}, abstractNote={ An 8-week-old male domestic shorthair was presented to the Internal Medicine Service at North Carolina State University for regurgitation. Radiographic diagnosis of generalized esophageal dilation and failure of esophageal peristalsis were compatible with diagnosis of congenital megaesophagus. Endoscopic examination of the esophagus revealed a fibrous stricture just orad to the lower esophageal sphincter. Conservative management to increase the body condition and size of the kitten consisted of feeding through a gastrostomy tube, during which time the esophagus regained normal peristaltic function, the stricture orifice widened in size and successful balloon dilatation of the stricture was performed. Esophageal endoscopy should be considered to rule out a stricture near the lower esophageal sphincter in kittens with radiographic findings suggestive of congenital megaesophagus. Management of such kittens by means of gastrostomy tube feeding may be associated with a return of normal esophageal motility and widening of the esophageal stricture, and facilitate subsequent success of interventional dilation of the esophageal stricture. }, number={6}, journal={JOURNAL OF FELINE MEDICINE AND SURGERY}, author={Schneider, Jaycie and Ames, Marisa and DiCicco, Michael and Savage, Mason and Atkins, Clarke and Wood, Michael and Gookin, Jody L.}, year={2015}, month={Jun}, pages={557–561} }
 @inbook{gookin_levy_2015, place={Lyon, France}, title={Trichomonosis}, ISBN={978-2-9550805-0-4}, booktitle={Parasitoses and Vector Borne Diseases of Cats}, publisher={Merial}, author={Gookin, J.L. and Levy, M.G.}, editor={Beugnet, F. and Halos, LEditors}, year={2015} }
 @article{tolbert_stauffer_brand_gookin_2014, title={Cysteine Protease Activity of Feline Tritrichomonas foetus Promotes Adhesion-Dependent Cytotoxicity to Intestinal Epithelial Cells}, volume={82}, ISSN={["1098-5522"]}, DOI={10.1128/iai.01671-14}, abstractNote={ABSTRACT}, number={7}, journal={INFECTION AND IMMUNITY}, author={Tolbert, M. K. and Stauffer, S. H. and Brand, M. D. and Gookin, J. L.}, year={2014}, month={Jul}, pages={2851–2859} }
 @inbook{gookin_2014, place={Guelph, Ontario}, title={Hooking up with some helminths}, ISBN={9780889556096}, booktitle={Sick! Curious tales of pests and parasites we share with animals}, publisher={Ontario Veterinary College, University of Guelph}, author={Gookin, J.L.}, editor={Stone, EA and Dewey, CEditors}, year={2014}, pages={162–166} }
 @inbook{gookin_lappin_2014, place={St. Louis, MO}, edition={15th}, title={Update on treatment of T. foetus and Giardia infections}, booktitle={Kirk's Current Veterinary Therapy XV}, publisher={Elsevier/Saunders}, author={Gookin, JL and Lappin, ME}, editor={Bonagura, J.D. and Twedt, D.C.Editors}, year={2014}, pages={528} }
 @article{tolbert_stauffer_gookin_2013, title={Feline Tritichomonas foetus adhere to the intestinal epithelium by receptor-ligand-dependent mechanisms}, volume={192}, ISSN={["1873-2550"]}, DOI={10.1016/j.vetpar.2012.10.019}, abstractNote={Tritrichomonas foetus (TF) is a protozoan that infects the feline ileum and colon resulting in chronic diarrhea. Up to 30% of young purebred cats are infected with TF and the infection is recognized as pandemic. Only a single drug, characterized by a narrow margin of safety and emerging development of resistance, is effective for treatment. While the venereal pathogenicity of bovine TF is attributed to adherence to uterovaginal epithelium, the pathogenesis of diarrhea in feline TF infection is unknown. The aim of this study was to establish an in vitro model of feline TF adhesion to intestinal epithelium. Confluent monolayers of porcine intestinal epithelial cells (IPEC-J2) were infected with axenic cultures of feline TF that were labeled with [(3)H] thymidine or CFSE and harvested at log-phase. The effect of multiplicity and duration of infection, viability of TF, binding competition, formalin fixation and cytoskeletal inhibitors on adherence of feline TF to IPEC-J2 monolayers was quantified by liquid scintillation counting and immunofluorescence. [(3)H] thymidine and CFSE-labeled TF reproducibly adhered to IPEC-J2 monolayers. Clinical isolates of feline TF adhered to the intestinal epithelium in significantly greater numbers than Pentatrichomonas hominis, the latter of which is a presumably nonpathogenic trichomonad. Adhesion of TF required viable trophozoites but was independent of cytoskeletal activity. Based on saturation and competition binding experiments, adherence of feline TF to the epithelium occurred via specific receptor-ligand interactions. The developed model provides a valuable resource for assessing pathogenic mechanisms of feline TF and developing novel pharmacologic therapies for blocking the adhesion of feline TF to the intestinal epithelium.}, number={1-3}, journal={Veterinary Parasitology}, author={Tolbert, M.K. and Stauffer, S.H. and Gookin, J.L.}, year={2013}, month={Feb}, pages={75–82} }
 @inbook{gookin_2013, place={St. Louis, MO}, edition={1st}, title={Infectious diseases of the large intestine}, booktitle={Canine and Feline Gastroenterology}, publisher={Elsevier Saunders}, author={Gookin, J.L.}, editor={Washabau, R.J. and Day, M.J.Editors}, year={2013}, pages={745–757} }
 @article{ghosh_borst_stauffer_suyemoto_moisan_zurek_gookin_2013, title={Mortality in Kittens Is Associated with a Shift in Ileum Mucosa-Associated Enterococci from Enterococcus hirae to Biofilm-Forming Enterococcus faecalis and Adherent Escherichia coli}, volume={51}, ISSN={["1098-660X"]}, DOI={10.1128/jcm.00481-13}, abstractNote={ABSTRACT}, number={11}, journal={JOURNAL OF CLINICAL MICROBIOLOGY}, author={Ghosh, Anuradha and Borst, Luke and Stauffer, Stephen H. and Suyemoto, Mitsu and Moisan, Peter and Zurek, Ludek and Gookin, Jody L.}, year={2013}, month={Nov}, pages={3567–3578} }
 @article{papich_levine_gookin_davidson_stagner_hayes_2013, title={Ronidazole pharmacokinetics in cats following delivery of a delayed-release guar gum formulation}, volume={36}, ISSN={["1365-2885"]}, DOI={10.1111/jvp.12019}, abstractNote={Ronidazole (RDZ) is the only known effective treatment for feline diarrhea caused by Tritrichomonas foetus. This study aimed to develop guar gum‐coated colon‐targeted tablets of RDZ and to determine the pharmacokinetics of this delayed‐release formulation in cats. Guar gum‐coated tablets were administered orally once to five healthy cats (mean dose 32.3 mg/kg). The tablets were then administered once daily for 5 days to four cats (mean dose 34.5 mg/kg), and absorption studies repeated on day 5. Plasma was collected and analyzed for RDZ concentration, and pharmacokinetic noncompartmental and deconvolution analysis were performed on the data. There was negligible RDZ release until after 6 h, and a delayed peak plasma concentration (mean Cmax 28.9 μg/mL) at approximately 14.5 h, which coincides with colonic arrival in cats. Maximum input rate (mg/kg per hour) occurred between 6 and 16 h. This delayed release of ronidazole from guar gum‐coated tablets indicates that release of RDZ may be delayed to deliver the medication to a targeted area of the intestine. Repeated dosing with guar gum tablets to steady‐state did not inhibit drug bioavailability or alter the pharmacokinetics. Such targeted RDZ drug delivery may provide improved efficacy and reduce adverse effects in cats.}, number={4}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Papich, M. G. and LeVine, D. N. and Gookin, J. L. and Davidson, G. S. and Stagner, W. C. and Hayes, R. B.}, year={2013}, month={Aug}, pages={399–407} }
 @article{tolbert_stauffer_gookin_2013, title={Sa1762 Cysteine Proteases of the Enteric Trichomonad Tritrichomonas Foetus Mediate Adhesion to Intestinal Epithelial Cells and Enterocyte Apoptosis}, volume={144}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(13)61074-4}, DOI={10.1016/S0016-5085(13)61074-4}, abstractNote={Tritrichomonas foetus (TF) is a lumen-dwelling protozoal pathogen that infects the feline ileum and large bowel. TF induces a chronic diarrhea similar to that observed in human giardiasis and other enteric protozoal diseases. Many of the mechanisms by which enteric protozoans colonize the intestine and induce epithelial injury are largely unknown. Thus, TF infection represents a novel model for the comparative study of human protozoal pathogenesis. Parasitic proteases are suspected to be key virulence factors for many enteric protozoans including TF. Study aims were to determine which classes of proteolytic activity are characteristic of feline TF and to determine the role of these proteases in TF survival, adherence to intestinal epithelial cells and consequent cytopathogenicity. The class-specific protease activities of protein extracts obtained from 3 feline TF and 1 feline Pentatrichomonas hominis isolate were identified by means of substrate-polyacrylamide gel electrophoresis in the presence or absence of cysteine (E64 0.01-0.6mM), metallo(EDTA 0.1-0.5mM), serine (PMSF 0.1-5mM; DFP 0.01-10mM; AEBSF 1-4mM) and aspartic (pepstatin A 0.01-0.1mM) protease inhibitors. The effect of protease inhibitors or their diluents on TF growth and adhesion was determined using feline TF labeled with [3H]thymidine that were allowed to adhere to monolayers of porcine intestinal epithelial cells (IPEC-J2) in co-culture. The cytopathogenic effect of TF was quantified by immunoblotting TF-infected IPEC-J2 cells for the M30 antigen of cleaved cytokeratin 18, which is a marker of apoptosis. A minimum of 3 replicates were performed for each experiment. Data were analyzed using Systat software (p ,0.05). Patterns of substrate-gel proteolysis, demonstrated by feline isolates of TF, were similar and revealed the presence of multiple high and low molecular weight proteases. On the basis of pharmacological inhibition, these activities were identified as serine (SP) and cysteine proteases (CP), respectively. P. hominis, a presumably non-pathogenic trichomonad, produced little protease activity compared to TF and had no CP activity. SP inhibition resulted in death of TF while CP inhibition blocked adhesion of TF to the intestinal epithelial cells and significantly inhibited enterocyte apoptosis. These studies establish that serine and cysteine proteases are the predominant mediators of feline TF proteolytic activity and identify the specific involvement of serine proteases in TF survival and cysteine proteases in TF adhesion and cytopathogenicity to intestinal epithelial cells. These findings have comparative implications for the further study of pharmacological serine and cysteine protease inhibitors for potential prevention, treatment or amelioration of enteric protozoal diseases and such investigations can be undertaken using a feline model of clinical infection.}, number={5}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Tolbert, Katie and Stauffer, Stephen and Gookin, Jody}, year={2013}, month={May}, pages={S-301} }
 @article{foster_stauffer_magness_gookin_2013, title={Tu2013 Characterization of Epithelial Cell Loss Due to Cryptosporidium Parvum Infection in a Non-Transformed Porcine Jejunal Enterocyte (IPEC-J2) Cell Line}, volume={144}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(13)63369-7}, DOI={10.1016/S0016-5085(13)63369-7}, abstractNote={infectious events 8 months after the first visit.Autopsy revealed multiple ulcerations throughout the gastrointestinal tract, some of which were accompanied by necrosis and perforation in the jejunum and ascending colon.Histologically, occlusive thrombotic angiopathy with endothelial cell degenerations was observed, consistent with gut perforation following infarction.According to the report by Cynthia et al. [1] we conducted an immunohistochemical analysis using Complement (C) 5b-9 antibody.Very interestingly, affected vessels were strongly positive for the antibody.Conclusion Our report clearly demonstrated C5-9mediated vascular injury led to gut ischemia leading to catastrophic outcome.}, number={5}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Foster, Derek M. and Stauffer, Stephen and Magness, Scott T. and Gookin, Jody}, year={2013}, month={May}, pages={S-904-S-905} }
 @article{levine_gookin_papich_davidson_2013, title={Twice-daily dosing of RDZ no longer recommended for treatment of intestinal Tritrichomonas foetus infection}, volume={16}, ISSN={1098-612X 1532-2750}, url={http://dx.doi.org/10.1177/1098612x13506430}, DOI={10.1177/1098612x13506430}, abstractNote={We would like to thank Xenoulis et al1 for their recent retrospective study in which information is provided on the outcome of cats that were treated with ronidazole for Tritrichomonas foetus infection. We agree with the authors’ recommendation of a treatment regimen for infections caused by T foetus of 30 mg/kg ronidazole (RDZ) q24h for 14 days.1 However, they reference a previous study of ours that recommended that cats that relapse should be treated with 30–50 mg/kg RDZ PO q12h.1,2 Based on our recent feline RDZ pharmacokinetic (PK) studies, we no longer recommend twice-daily dosing of RDZ.3 In our PK study, we determined that the half-life of RDZ is long (10.5 h), and that 48 h after a single dose of 30 mg/kg immediaterelease RDZ capsules orally there was still drug remaining in the cats’ plasma.3 Simulations based on our PK studies showed that twice-daily administration of 30 mg/kg RDZ PO would lead to drug accumulation.3 Neurotoxicity, including tremors, ataxia and agitation, is a reported and potentially dangerous side effect of RDZ in cats.4,5 As such, we no longer advocate twice-daily RDZ at this dose. However, it should also be noted that our PK studies did not assess the efficacy of our revised recommendations of once-daily 30 mg/kg RDZ administration for T foetus-infected cats. Such work remains to be done. We wanted to draw readers’ attention to these recent PK studies, so that cats are not inadvertently overdosed and risk neurologic sequelae based on outdated recommendations. References 1 Xenoulis PG, Lopinski DJ, Read SA, et al. Intestinal Tritrichomonas foetus infection in cats: a retrospective study of 104 cases. J Feline Med Surg 2013; 15: 1098–1103. 2 Gookin JL, Copple CN, Papich MG, et al. Efficacy of ronidazole for treatment of feline Tritrichomonas foetus infection. J Vet Intern Med 2006; 20: 536–543. 3 LeVine DN, Papich MG, Gookin JL, et al. Ronidazole pharmacokinetics after intravenous and oral immediaterelease capsule administration in healthy cats. J Feline Med Surg 2011; 13: 244–250. 4 Rosado TW, Specht A and Marks SL. Neurotoxicosis in four cats receiving ronidazole. J Vet Intern Med 2007; 21: 328–331. 5 Pham D. Chronic intermittent diarrhea in a 14-month-old Abyssinian cat. Can Vet J 2009; 50: 85–87.}, number={2}, journal={Journal of Feline Medicine and Surgery}, publisher={SAGE Publications}, author={LeVine, Dana N and Gookin, Jody L and Papich, Mark G and Davidson, Gigi S}, year={2013}, month={Oct}, pages={198–198} }
 @article{hutchins_breitschwerdt_cullen_bissett_gookin_2012, title={Limited yield of diagnoses of intrahepatic infectious causes of canine granulomatous hepatitis from archival liver tissue}, volume={24}, ISSN={1040-6387 1943-4936}, url={http://dx.doi.org/10.1177/1040638712453583}, DOI={10.1177/1040638712453583}, abstractNote={ Canine granulomatous hepatitis is an uncommon morphologic diagnosis that has been associated with a variety of diseases, including a number of systemic infectious etiologies. Formalin-fixed, paraffin-embedded (FFPE) tissues are typically the only source of liver tissue remaining for additional testing for the presence of infectious disease within granulomas. It is unclear if the more common infectious culprits of granulomatous hepatitis can be identified from such specimens. The aim of the current study was to retrospectively investigate archival FFPE liver tissue from dogs with granulomatous hepatitis for the presence of infectious agents. Semiquantitative analysis of copper accumulation in liver specimens was also performed. Medical records were examined for recorded evidence of systemic infectious disease diagnosis. Formalin-fixed, paraffin-embedded liver was prospectively evaluated for infectious agents via differential staining techniques ( n = 13), eubacterial fluorescent in situ hybridization ( n = 11), and Bartonella polymerase chain reaction assays ( n = 15). An infectious cause of granulomatous hepatitis was not identified within liver tissue from any dog using these diagnostic methodologies. Six out of 25 (24%) dogs were diagnosed with concurrent systemic or localized bacterial infections at the time of presentation. Nine out of 17 (53%) dogs had excessive hepatic copper accumulation when evaluated by a semiquantitative histologic grading scheme or quantitative copper analysis. As definitive infectious causes of granulomatous hepatitis were not identified within archival liver biopsy samples, it was concluded that investigation of infectious etiologies within FFPE liver specimens using these diagnostic approaches may be of low yield. }, number={5}, journal={Journal of Veterinary Diagnostic Investigation}, publisher={SAGE Publications}, author={Hutchins, Rae G. and Breitschwerdt, Edward B. and Cullen, John M. and Bissett, Sally A. and Gookin, Jody L.}, year={2012}, month={Aug}, pages={888–894} }
 @article{foster_nielsen_stauffer_gookin_2012, title={Mo1784 The In Vivo Transcriptional Response of Intestinal Epithelium to C. Parvum Infection is Dominated by Interferon-Alpha Signaling Pathways}, volume={142}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(12)62638-9}, DOI={10.1016/S0016-5085(12)62638-9}, abstractNote={mast cells were significantly reduced in the TI compared to ex-smokers (median counts: 231 vs 324, p=<0.004) and non-smokers (median: 231 vs 342, p=<0.03); in the cecum of smokers, compared to ex-smokers (median: 116 vs 158, p=<0.007) or non-smokers (median: 116 vs 170, p=<0.0002).Mast cells were significantly reduced in D1 of smokers, compared to non-smokers (median: 167 vs 238, p=<0.01).There was a tendency for eosinophilia in D1 of smokers (p=0.055).Eosinophils were not significantly altered in the TI/colon of smokers.CONCLUSIONS: Smoking is associated with disordered homeostasis of gastrointestinal mucosal mast cells, seen in small intestinal and ileocolic regions, sites most commonly affected in CD.Our data suggest that chronic exposure to tobacco may subtly alter the balance of mucosal innate immunity, particularly mast cells.1.}, number={5}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Foster, Derek and Nielsen, Dahlia and Stauffer, Stephen and Gookin, Jody}, year={2012}, month={May}, pages={S-684} }
 @article{foster_stauffer_stone_gookin_2012, title={Proteasome Inhibition of Pathologic Shedding of Enterocytes to Defend Barrier Function Requires X-Linked Inhibitor of Apoptosis Protein and Nuclear Factor κB}, volume={143}, ISSN={0016-5085}, url={http://dx.doi.org/10.1053/j.gastro.2012.03.030}, DOI={10.1053/j.gastro.2012.03.030}, abstractNote={BACKGROUND & AIMS
Although we are beginning to understand where, when, and how intestinal epithelial cells are shed, physiologically, less is understood about alterations in cell fate during minimally invasive epithelial infections. We used a piglet model of Cryptosporidium parvum infection to determine how elimination of infected enterocytes is balanced with the need to maintain barrier function.


METHODS
We studied the effects of enterocyte shedding by C parvum-infected ileum on barrier function ex vivo with Ussing chambers. The locations and activities of caspase-3, nuclear factor κB (NF-κB), and inhibitor of apoptosis proteins (IAP) were assayed by enzyme-linked immunosorbent assay, immunoblot, and tissue immunoreactivity analyses and using specific pharmacologic inhibitors. The location, specificity, and magnitude of enterocyte shedding were quantified using special stains and light microscopy.


RESULTS
Infection with C parvum activated apoptotic signaling pathways in enterocytes that resulted in cleavage of caspase-3. Despite caspase-3 cleavage, enterocyte shedding was confined to villus tips, coincident with apoptosis, and observed more frequently in infected cells. Epithelial expression of X-linked inhibitor of apoptosis protein (XIAP), activation of NF-κB, and proteasome activity were required for control of cell shedding and barrier function. The proteasome blocked activity of caspase-3; this process was mediated by expression of XIAP, which bound to cleaved caspase-3.


CONCLUSIONS
We have identified a pathway by which villus epithelial cells are maintained during C parvum infection. Loss of barrier function is reduced by active retention of infected enterocytes until they reach the villus tip. These findings might be used to promote clearance of minimally invasive enteropathogens, such as by increasing the rate of migration of epithelial cells from the crypt to the villus tip.}, number={1}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Foster, Derek M. and Stauffer, Stephen H. and Stone, Maria R. and Gookin, Jody L.}, year={2012}, month={Jul}, pages={133–144.e4} }
 @article{tolbert_leutenegger_lobetti_birrell_gookin_2012, title={Species identification of trichomonads and associated coinfections in dogs with diarrhea and suspected trichomonosis}, volume={187}, ISSN={["0304-4017"]}, DOI={10.1016/j.vetpar.2011.12.031}, abstractNote={Trichomonads have been infrequently reported in the feces of dogs where their pathogenicity remains uncertain. It is currently unknown whether Tritrichomonas foetus or Pentatrichomonas hominis is identified more commonly in dogs with trichomonosis or how often these infections are accompanied by concurrent enteric infectious agents. The objective of this study was to determine the identity of trichomonads present in a series of 38 unsolicited canine diarrheic fecal samples submitted for T. foetus diagnostic polymerase chain reaction (PCR) testing between 2007 and 2010. We also examined each fecal sample for an association of trichomonosis with concurrent infection using a convenient real-time PCR panel for nine gastrointestinal pathogens. P. hominis, T. foetus, or both were identified by PCR in feces of 17, 1, and 1 dogs respectively. Feces from the remaining 19 dogs were PCR negative for T. foetus, P. hominis and using broader-spectrum Trichomonadida primers. The total number and specific identities of concurrent enteropathogens identified did not differ between fecal samples from dogs that were or were not identified by PCR as infected with trichomonads. These results suggest that P. hominis infection is more frequently identified than T. foetus infection in diarrheic dogs with trichomonosis and that concurrent enteropathogen infection is common in this population.}, number={1-2}, journal={VETERINARY PARASITOLOGY}, author={Tolbert, M. K. and Leutenegger, C. M. and Lobetti, R. and Birrell, J. and Gookin, J. L.}, year={2012}, month={Jun}, pages={319–322} }
 @inbook{gookin_2012, place={St. Louis, MO}, edition={4th}, title={Trichomoniasis}, booktitle={Infectious Diseases of the Dog and Cat}, publisher={Elsevier Saunder}, author={Gookin, J.L.}, editor={Green, C.E.Editor}, year={2012}, pages={797–801} }
 @article{tolbert_gookin_2012, title={Tu1855 Tritrichomonas Foetus ADHERE to Intestinal Epithelium by Sialic Acid and Cysteine Protease-Dependent Mechanisms}, volume={142}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(12)63342-3}, DOI={10.1016/S0016-5085(12)63342-3}, number={5}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Tolbert, Katie and Gookin, Jody}, year={2012}, month={May}, pages={S-861-S-862} }
 @article{wood_breitschwerdt_nordone_linder_gookin_2012, title={Uropathogenic E. coli Promote a Paracellular Urothelial Barrier Defect Characterized by Altered Tight Junction Integrity, Epithelial Cell Sloughing and Cytokine Release}, volume={147}, ISSN={0021-9975}, url={http://dx.doi.org/10.1016/j.jcpa.2011.09.005}, DOI={10.1016/j.jcpa.2011.09.005}, abstractNote={The urinary bladder is a common site of bacterial infection with a majority of cases attributed to uropathogenic Escherichia coli. Sequelae of urinary tract infections (UTIs) include the loss of urothelial barrier function and subsequent clinical morbidity secondary to the permeation of urine potassium, urea and ammonia into the subepithelium. To date there has been limited research describing the mechanism by which this urothelial permeability defect develops. The present study models acute uropathogenic E. coli infection in vitro using intact canine bladder mucosa mounted in Ussing chambers to determine whether infection induces primarily a transcellular or paracellular permeability defect. The Ussing chamber sustains tissue viability while physically separating submucosal and lumen influences, so this model is ideal for quantitative measurement of transepithelial electrical resistance (TER) to assess alterations of urothelial barrier function. Using this model, changes in both tissue ultrastructure and TER indicated that uropathogenic E. coli infection promotes a paracellular permeability defect associated with the failure of umbrella cell tight junction formation and umbrella cell sloughing. In addition, bacterial interaction with the urothelium promoted secretion of cytokines from the urinary bladder with bioactivity capable of modulating epithelial barrier function including tumour necrosis factor-α, interleukin (IL)-6 and IL-15. IL-15 secretion by the infected bladder mucosa is a novel finding and, because IL-15 plays key roles in reconstitution of tight junction function in damaged intestine, this study points to a potential role for IL-15 in UTI-induced urothelial injury.}, number={1}, journal={Journal of Comparative Pathology}, publisher={Elsevier BV}, author={Wood, M.W. and Breitschwerdt, E.B. and Nordone, S.K. and Linder, K.E. and Gookin, J.L.}, year={2012}, month={Jul}, pages={11–19} }
 @article{azcarate-peril_foster_cadenas_stone_jacobi_stauffer_pease_gookin_2011, title={Acute necrotizing enterocolitis of preterm piglets is characterized by dysbiosis of ileal mucosa-associated bacteria}, volume={2}, ISSN={1949-0976 1949-0984}, url={http://dx.doi.org/10.4161/gmic.2.4.16332}, DOI={10.4161/gmic.2.4.16332}, abstractNote={Investigation of bacteria involved in pathogenesis of necrotizing enterocolitis (NEC) is limited by infant fragility, analysis restricted to feces, use of culture-based methods, and lack of clinically-relevant animal models. This study used a unique preterm piglet model to characterize spontaneous differences in microbiome composition of NEC-predisposed regions of gut. Preterm piglets (n=23) were cesarean-delivered and nurtured for 30 hours over which time 52% developed NEC. Bacterial DNA from ileal content, ileal mucosa, and colonic mucosa were PCR amplified, subjected to terminal restriction fragment length polymorphism (TRFLP) analysis and targeted 16S rDNA qPCR. Preterm ileal mucosa was specifically bereft in diversity of bacteria compared to ileal content and colonic mucosa. Preterm ileum was restricted to representation by only Proteobacteria, Firmicutes, Cyanobacteria and Chloroflexi. In piglets with NEC, ileal mucosa was uniquely characterized by increases in number of Firmicutes and diversity of phyla to include Actinobacteria and uncultured bacteria. Five specific TRFLP profiles, corresponding in closest identity to Clostridium butyricum, C. neonatale, C. proteolyticum, Streptomyces spp., and Leptolyngbya spp., were significantly more prevalent or observed only among samples from piglets with NEC. Total numbers of Clostridium spp. and C. butyricum were significantly greater in samples of NEC ileal mucosa but not ileal content or colonic mucosa. These results provide strong support for ileal mucosa as a focus for investigation of specific dysbiosis associated with NEC and suggest a significant role for Clostridium spp., and members of the Actinobacteria and Cyanobacteria in the pathogenesis of NEC in preterm piglets.}, number={4}, journal={Gut Microbes}, publisher={Informa UK Limited}, author={Azcarate-Peril, M. Andrea and Foster, Derek M. and Cadenas, Maria B. and Stone, Maria R. and Jacobi, Sheila K. and Stauffer, Stephen H. and Pease, Anthony and Gookin, Jody L.}, year={2011}, month={Jul}, pages={234–243} }
 @article{foster_stauffer_stone_gookin_2011, title={NFkB-Mediated Expression of XIAP Inhibits Caspase-3-Dependent Shedding of Intestinal Epithelial Cells in Defense of Barrier Function in Cryptosporidium Parvum Infection}, volume={140}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(11)62085-4}, DOI={10.1016/S0016-5085(11)62085-4}, number={5}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Foster, Derek and Stauffer, Stephen and Stone, Maria and Gookin, Jody}, year={2011}, month={May}, pages={S-503} }
 @article{azcarate-peril_foster_cadenas_stone_jacobi_stauffer_pease_gookin_2011, title={Necrotizing Enterocolitis of Preterm Piglets is Characterized by a Unique Ileum Mucosa-Associated Microbiome}, volume={140}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(11)62764-9}, DOI={10.1016/S0016-5085(11)62764-9}, number={5}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Azcarate-Peril, M. Andrea and Foster, Derek and Cadenas, Maria B. and Stone, Maria and Jacobi, Sheila and Stauffer, Stephen and Pease, Anthony and Gookin, Jody}, year={2011}, month={May}, pages={S-666} }
 @article{levine_papich_gookin_davidson_davis_hayes_2011, title={Ronidazole pharmacokinetics after intravenous and oral immediate-release capsule administration in healthy cats}, volume={13}, ISSN={["1532-2750"]}, DOI={10.1016/j.jfms.2010.12.001}, abstractNote={Ronidazole (RDZ) is an effective treatment for feline Tritrichomonas foetus infection, but has produced neurotoxicity in some cats. An understanding of the disposition of RDZ in cats is needed in order to make precise dosing recommendations. Single-dose pharmacokinetics of intravenous (IV) RDZ and immediate-release RDZ capsules were evaluated. A single dose of IV RDZ (mean 9.2 mg/kg) and a 95 mg immediate-release RDZ capsule (mean 28.2 mg/kg) were administered to six healthy cats in a randomized crossover design. Plasma samples were collected for 48 h and assayed for RDZ using high pressure liquid chromatography (HPLC). Systemic absorption of oral RDZ was rapid and complete, with detection in the plasma of all cats by 10 min after dosing and a bioavailability of 99.64 (±16.54)%. The clearance of RDZ following IV administration was 0.82 (±0.07) ml/kg/min. The terminal half-life was 9.80 (±0.35) and 10.50 (±0.82) h after IV and oral administration, respectively, with drug detectable in all cats 48 h after both administrations. The high oral bioavailability of RDZ and slow elimination may predispose cats to neurotoxicity with twice-daily administration. Less frequent administration should be considered for further study of effective treatment of T foetus-infected cats.}, number={4}, journal={JOURNAL OF FELINE MEDICINE AND SURGERY}, author={LeVine, Dana N. and Papich, Mark G. and Gookin, Jody L. and Davidson, Gigi S. and Davis, Jennifer L. and Hayes, Rebecca B.}, year={2011}, month={Apr}, pages={244–250} }
 @article{gray_hunter_stone_gookin_2010, title={Assessment of reproductive tract disease in cats at risk for Tritrichomonas foetus infection}, volume={71}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.71.1.76}, abstractNote={Abstract}, number={1}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Gray, Sara G. and Hunter, Stuart A. and Stone, Maria R. and Gookin, Jody L.}, year={2010}, month={Jan}, pages={76–81} }
 @article{wood_breitschwerdt_gookin_2010, title={Autocrine Effects of Interleukin-6 Mediate Acute-Phase Proinflammatory and Tissue-Reparative Transcriptional Responses of Canine Bladder Mucosa}, volume={79}, ISSN={0019-9567 1098-5522}, url={http://dx.doi.org/10.1128/IAI.01102-10}, DOI={10.1128/iai.01102-10}, abstractNote={ABSTRACT}, number={2}, journal={Infection and Immunity}, publisher={American Society for Microbiology}, author={Wood, Michael W. and Breitschwerdt, Edward B. and Gookin, Jody L.}, editor={Bäumler, A. J.Editor}, year={2010}, month={Nov}, pages={708–715} }
 @article{gookin_stauffer_dybas_cannon_2010, title={Documentation of In Vivo and In Vitro Aerobic Resistance of Feline Tritrichomonas foetus Isolates to Ronidazole}, volume={24}, ISSN={["1939-1676"]}, DOI={10.1111/j.1939-1676.2010.0534.x}, abstractNote={BACKGROUND
The mainstays of treatment for clinically important trichomonad infections are the 5-nitroimidazoles. Metronidazole resistance of feline Tritrichomonas foetus is presumed because of common treatment failure, and tinidazole does not consistently eradicate infection. To date, ronidazole is the only drug demonstrated as effective for treatment of cats infected with T. foetus.


OBJECTIVE
To document in vivo treatment failure and identify underlying causes and in vitro conditions of resistance of feline T. foetus to ronidazole.


ANIMALS
Two intact male Abyssinians failing>or=5 courses of treatment with increasing doses of 5-nitroimidazole drugs. An intact male Abyssinian documented to clear infection after treatment with a single course of ronidazole.


METHODS
T. foetus isolates were cultured from feces and tested in vitro for susceptibility to ronidazole under aerobic and anaerobic culture conditions. A urogenital nidus of T. foetus infection was investigated by culture, polymerase chain reaction, or immunohistochemical testing of urogenital specimens.


RESULTS
Resistance to ronidazole under aerobic conditions was uniquely identified in T. foetus isolated from cats with well-documented treatment failure. Treatment failure could not be attributed to reinfection, inappropriate treatment protocol, or presence of a urogenital nidus of infection.


CONCLUSIONS AND CLINICAL IMPORTANCE
Clinical resistance to metronidazole, low efficacy of tinidazole, and present documentation of in vivo and in vitro resistance to ronidazole in some cats are consistent with a high level of cross resistance of feline T. foetus to 5-nitroimidazole drugs. Current lack of alternative drugs with clinical efficacy against feline T. foetus suggests that active investigation of other treatment approaches is warranted.}, number={4}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Gookin, J. L. and Stauffer, S. H. and Dybas, D. and Cannon, D. H.}, year={2010}, pages={1003–1007} }
 @article{gookin_stone_yaeger_meyerholz_moisan_2010, title={Fluorescence in situ hybridization for identification of Tritrichomonas foetus in formalin-fixed and paraffin-embedded histological specimens of intestinal trichomonosis}, volume={172}, ISSN={["0304-4017"]}, DOI={10.1016/j.vetpar.2010.04.014}, abstractNote={In the present study a highly species-specific oligonucleotide sequence of Tritrichomonas foetus 18S rRNA was used to design an antisense probe for identification of T. foetus in formalin-fixed and paraffin-embedded histological specimens by means of fluorescence in situ hybridization (FISH). Using archival histological specimens from several species with light microscopic evidence of intestinal trichomoniasis, and under optimized hybridization conditions, the probe positively identified trichomonads in colonic specimens from piglets and a kitten with PCR-confirmed T. foetus infection. Neither positive hybridization of the probe or PCR amplification of T. foetus DNA was observed in histological specimens from hamster (Tritrichomonas muris), turkey, nor mouse (Entamoeba muris) intestinal protozoal infections. Sequence-specific binding of the probe was further verified by successfully out-competing the hybridization with 10 x molar excess unlabeled probe and failure of a labeled sense probe to hybridize. The FISH assay described here enables simultaneous location and molecular identification of T. foetus in formalin-fixed and paraffin-embedded histological specimens of intestinal trichomoniasis. The methods employed are likely to also be applicable to probes designed for specific recognition of other trichomonad species, especially in mammalian tissue where red blood cell auto-fluorescence can be easily differentiated from the hybridization signal of trichomonads.}, number={1-2}, journal={VETERINARY PARASITOLOGY}, author={Gookin, J. L. and Stone, M. R. and Yaeger, M. J. and Meyerholz, D. K. and Moisan, Peter}, year={2010}, month={Aug}, pages={139–143} }
 @article{nicklas_moisan_stone_gookin_2010, title={In Situ Molecular Diagnosis and Histopathological Characterization of Enteroadherent Enterococcus hirae Infection in Pre-Weaning-Age Kittens}, volume={48}, ISSN={["1098-660X"]}, DOI={10.1128/jcm.00916-09}, abstractNote={ABSTRACT}, number={8}, journal={JOURNAL OF CLINICAL MICROBIOLOGY}, author={Nicklas, Jodi L. and Moisan, Peter and Stone, Maria R. and Gookin, Jody L.}, year={2010}, month={Aug}, pages={2814–2820} }
 @article{nordone_gookin_2010, title={Lymphocytes and not IFN-gamma mediate expression of iNOS by intestinal epithelium in murine cryptosporidiosis}, volume={106}, ISSN={["0932-0113"]}, DOI={10.1007/s00436-010-1837-7}, abstractNote={We hypothesized that unrecognized differences in epithelial expression of inducible nitric oxide synthase (iNOS), resulting from engineered immunodeficiency, could explain the contradictory findings of prior studies regarding the importance of nitric oxide (NO) in murine models of Cryptosporidium parvum infection. Severe combined immunodeficient mice (SCID) failed to constitutively or inducibly express epithelial iNOS or increase NO synthesis in response to C. parvum infection. In contrast, mice lacking IFN-γ alone induced both epithelial iNOS expression and NO synthesis in response to infection. Accordingly, lymphocytes mediate epithelial expression of iNOS and NO synthesis independent of IFN-γ in response to C. parvum infection. These findings in large part explain the contradictory conclusions of prior studies regarding the role of iNOS in C. parvum infection.}, number={6}, journal={PARASITOLOGY RESEARCH}, author={Nordone, Shila K. and Gookin, Jody L.}, year={2010}, month={May}, pages={1507–1511} }
 @article{gookin_mcwhorter_vaden_posner_2010, title={Outcome assessment of a computer-animated model for learning about the regulation of glomerular filtration rate}, volume={34}, ISSN={["1043-4046"]}, DOI={10.1152/advan.00012.2010}, abstractNote={ The regulation of the glomerular filtration rate (GFR) is a particularly important and challenging concept for students to integrate into a memorable framework for building further knowledge and solving clinical problems. In this study, 76 first-year veterinary students and 19 veterinarians in clinical specialty training (house officers) participated in separate online exercises to evaluate the use of a computer-animated model of GFR regulation ( www.aamc.org/mededportal ) on learning outcome. Students were randomly allocated to study either the animated model or written materials before completion of a 10-question multiple-choice quiz. House officers completed a 35-question test before and after study of the animated model. Both groups completed a survey about the learning exercise. The ability of the model to enhance learning was demonstrated by a significant improvement ( P < 0.001) in the test performance of house officers after studying the model. The model performed similarly to written materials alone in affecting the subsequent quiz performance of the students. The majority of students and house officers agreed or strongly agreed that the animated model was easy to understand, improved their knowledge and appreciation of the importance of GFR regulation, and that they would recommend the model to peers. Most students [63 of 76 students (83%)] responded that they would prefer the use of the animated model alone over the study of written materials but acknowledged that a combination of hardcopy written notes and the animated model would be ideal. A greater applicability of the model to more advanced students and an introduction in a didactic setting before individual study were suggested by the house officers. The results of this study suggest that the animated model is a useful, effective, and well-received tool for learning and creating a visual memory of the regulatory mechanisms of GFR. }, number={2}, journal={ADVANCES IN PHYSIOLOGY EDUCATION}, author={Gookin, Jody L. and McWhorter, Dan and Vaden, Shelly and Posner, Lysa}, year={2010}, month={Jun}, pages={97–105} }
 @article{gookin_foster_harvey_mcwhorter_2009, title={An Animated Model of Reticulorumen Motility}, volume={36}, ISSN={["0748-321X"]}, url={https://doi.org/10.3138/jvme.36.4.444}, DOI={10.3138/jvme.36.4.444}, abstractNote={ Understanding reticulorumen motility is important to the assessment of ruminant health and optimal production, and in the recognition, diagnosis, and treatment of disease. Accordingly, the teaching of reticulorumen motility is a staple of all veterinary curricula. This teaching has historically been based on written descriptions, line drawings, or pressure tracings obtained during contraction sequences. We developed an animated model of reticulorumen motility and hypothesized that veterinary students would prefer use of the model over traditional instructional methods. First-year veterinary students were randomly allocated to one of two online learning exercises: with the animated model (Group A) or with text and line drawings (Group B) depicting reticulorumen motility. Learning was assessed with a multiple-choice quiz and feedback on the learning alternatives was obtained by survey. Seventy-four students participated in the study, including 38/42 in Group A and 36/36 in Group B. Sixty-four out of 72 students (89%) responded that they would prefer use of the animated model if only one of the two learning methods was available. A majority of students agreed or strongly agreed that the animated model was easy to understand and improved their knowledge and appreciation of the importance of reticulorumen motility, and would recommend the model to other veterinary students. Interestingly, students in Group B achieved higher scores on examination than students in Group A. This could be speculatively attributed to the inclusion of an itemized list of contraction sequences in the text provided to Group B and failure of Group A students to read the text associated with the animations. }, number={4}, journal={JOURNAL OF VETERINARY MEDICAL EDUCATION}, author={Gookin, Jody L. and Foster, Derek M. and Harvey, Alice M. and McWhorter, Dan}, year={2009}, pages={444–450} }
 @inbook{davis_gookin_2009, place={Ames, Iowa}, edition={9th}, title={Antiprotozoal Drugs}, booktitle={Veterinary Pharmacology and Therapeutics}, publisher={Blackwell Publishing}, author={Davis, JL and Gookin, JL}, editor={Riviere, J.E. and Papich, M.G.Editors}, year={2009}, pages={1145–1179} }
 @article{levine_zhou_ghiloni_fields_birkenheuer_gookin_roberston_malloy_feldman_2009, title={Hereditary 1,25-Dihydroxyvitamin D-Resistant Rickets in a Pomeranian Dog Caused by a Novel Mutation in the Vitamin D Receptor Gene}, volume={23}, ISSN={["1939-1676"]}, DOI={10.1111/j.1939-1676.2009.0405.x}, abstractNote={Hypocalcemic rickets encompasses a group of disorders in which intestinal absorption of calcium is insufficient to meet the calcium demands of a growing skeleton. Causes include dietary calcium deficiency and insufficient intestinal absorption of calcium caused by vitamin D deficiency or decreased vitamin D activity. Hereditary disorders of vitamin D documented in humans include vitamin D-dependent rickets type I (VDDR-I), in which there is a deficiency of the renal enzyme (1α-hydroxylase) that converts 25-hydroxyvitamin D3 to the active hormone 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3 or calcitriol) and vitamin D-dependent rickets type II (VDDR-II) in which there is end-organ resistance to the active hormone. The latter is usually secondary to defects in the vitamin D receptor (VDR). VDDR-II is currently more commonly termed hereditary vitamin D-resistant rickets (HVDRR). We describe a case of rickets in a juvenile dog that led us to investigate potential hereditary vitamin D disorders and resulted in the documentation of HVDRR in a dog. The disease is characterized by hypocalcemia, secondary hyperparathyroidism, hypomineralization of bones, rickets, and in some cases, alopecia. An intact female Pomeranian dog was initially evaluated by one of the authors at 2 months of age for nonpruritic alopecia of the head and rear limbs. The remainder of the dog's physical examination at that time was unremarkable. A skin scraping was negative. The dog and her half-sibling (same sire, different dam) had been obtained from a breeder a few days before examination. The half-sibling was the same age as the affected dog, and was normal in appearance. Both dogs were eating a commercial puppy food. At 4 months of age, the affected dog appeared to tire easily when playing. On physical examination, there was lateral bowing of the antebrachium of both forelimbs and palpable thickening of the distal radii. The alopecia had become more generalized and remained nonpruritic (Fig 1). A serum biochemistry profile revealed marked hypocalcemia (total calcium 5.5 mg/dL; reference range 8.9–11.4 mg/dL) with a normal albumin concentration, hyperphosphatemia (phosphate 7.3 mg/dL; reference range 2.5–6 mg/dL), and increased alkaline phosphatase (ALP) (829 U/L; reference range 5–131 U/L). Blood urea nitrogen (BUN) and creatinine, complete blood count, and serum thyroxine (total thyroxine 2.7 μg/dL; reference range 1.0–4.0 μg/dL) were all within normal limits. Photograph of the affected dog at 3 months of age demonstrating the remarkable alopecia. The photograph shows partial alopecia on the ventral chest, in the perineal area, and on the caudo-medial aspect of thighs. In the areas where hair is present, it is thin, likely because of a decreased amount of secondary hairs. The normal half-sibling is pictured to the right for comparison. The dog was reevaluated at 5 months of age for intermittent lameness while playing. Although her alopecia was resolving, her abnormal forelimb conformation persisted. Radiographs showed widening and abnormal lucency (decreased mineralization) of the distal radial and ulnar physes, with sclerosis and widening of the adjacent epiphyses and metaphyses (Fig 2A and B). Persistent hypocalcemia (total calcium 5.7 mg/dL) and low-ionized calcium (0.66 mmol/L; reference range 1.24–1.43 mmol/L) were documented, along with hyperparathyroidism (intact parathyroid hormone [PTH] 739 pg/mL; reference range 27–155 pg/mL).a Pre- and postprandial serum concentrations of bile acids were within reference range. On the basis of hypocalcemia, hyperparathyroidism, and the skeletal abnormalities, a provisional diagnosis was a vitamin D-dependent form of rickets. Treatment with oral calcium supplementation (calcium carbonateb 29 mg/kg PO q24h) and 1,25(OH)2D3c (43 ng/kg PO q24h) was initiated. Lateral (A) and dorsopalmar (B) radiographs of the right carpus acquired at 5 months of age before initiation of treatment. There is widening and increased lucency of the distal radial and ulnar physes with irregular (frayed) metaphyseal margins and flaring of the adjacent epiphyses and metaphyses. Lateral (C) and dorsopalmar (D) radiographs of the right carpus acquired at 8.5 months of age, 3.5 months after initiation of treatment. The distal antebrachial physes appear more normal in width, opacity, and margination. Evidence of distal metaphyseal remodeling is present. Total serum calcium concentrations were persistently low (ranging from 4.9 to 6.2 mg/dL) despite consistent increases in oral calcium and 1,25(OH)2D3 supplementation to doses well above standard recommendations (25–50 mg/kg/d of calcium carbonate and 20–30 ng/kg/d 1,25(OH)2D3)1 (Table 1). At 7 months of age, the dog had a generalized seizure that was controlled by administration of diazepam. At the time of the seizure, total serum calcium concentration was 5.7 mg/dL (reference range 7.9–12 mg/dL).d The dog was referred to the Internal Medicine Service of North Carolina State University, College of Veterinary Medicine (NCSU CVM) for further evaluation. On examination, the dog was bright and alert and interactive. Her conformation was unusual, with the forelimbs being shorter than the hind limbs, and slightly bowed laterally. Despite prior resolution of the alopecia, the affected dog's coat was of poorer quality than that of her half-sibling. The remainder of the physical examination was unremarkable. A serum biochemistry profile confirmed persistent hypocalcemia (6.3 mg/dL; reference range 9.2–11.6 mg/dL), with normal serum phosphorous concentration (5.7 mg/dL; 2–6.7 mg/dL) and renal values (BUN and creatinine). There was high PTH (91 pmol/L; 3–17 pmol/L),e increased ALP (486 U/L; 14–120 U/L), low 25-hydroxyvitamin D (43 nmol/L; 60–215 nmol/L),e and low-ionized calcium (0.94 mmol/L; 1.25–1.45 mmol/L)e concentration in serum. Rickets due to vitamin D resistance was suspected because of the lack of response to high-dose therapy with 1,25(OH)2D3. Since the dog did not respond to oral calcium supplementation, calcium (12.5 mg/kg SQ q24h)f was administered parenterally. 1,25(OH)2D3 therapy (75 ng/kg PO q24h) was continued. At 8 months of age, while still receiving 1,25(OH)2D3, serum 1,25(OH)2D3 concentrationg was measured to definitively differentiate between vitamin D deficiency and the two types of vitamin D-dependent rickets, type-I and type-II (HVDRR). The dog's serum 1,25(OH)2D3 concentration was over 20-fold greater than the upper end of the reference range (1,017 pb/mL; 25–50 pg/mL) despite persistent hypocalcemia (total calcium 5.4 mg/dL; 8.9–11.4 mg/dL). The increased concentration of 1,25 (OH)2D3 was consistent with a diagnosis of HVDRR. In this case, even though the dog was being supplemented with 1,25(OH)2D3, HVDRR was considered likely because high-circulating concentrations of 1,25(OH)2D3 were ineffective in raising serum calcium concentrations, confirming 1,25(OH)2D3 resistance. Oral calcium carbonate therapy was reinitiated at this time (75 mg/kg PO q24h) in addition to the 1,25(OH)2D3 supplementation and daily SQ calcium injections. At 8.5 months of age, the dog became acutely paraplegic in the hind limbs and depressed. The dog was evaluated by her local veterinarian, where total calcium concentration was determined to be 4.0 mg/dL (reference range 7.9–12 mg/dL). The veterinarian administered calcium IM (25 mg/kg IM once)f and referred the dog to the Emergency Service at NCSU. On examination, the dog was opisthotonic and tetanic, stuporous, weak, and believed to be having frequent focal seizures. Ionized calcium was 0.61 mmol/L (reference range 1.11–1.40 mmol/L). Calcium gluconate (100 mg/kg IV once)h was administered slowly, followed by a continuous rate infusion of calcium (10 mg/kg/h IV).h The dog continued to have seizure-like activity and muscle tetany, despite normalization of serum-ionized calcium (0.91 mmol/L) and a normal ECG. Tetany and seizure activity were controlled with midazolami (0.5 mg/kg IV once, then 0.3 mg/kg/h IV). After initial stabilization, a neurologic examination revealed signs attributable to diffuse forebrain disease (variably obtunded to stuporous, intermittent lateral strabismus in both eyes, bilateral miotic pupils, and reduced nasal sensation bilaterally) and hind limb paresis (exaggerated pelvic limb segmental spinal reflexes, absent deep pain in both pelvic limbs and the tail). The forebrain signs were attributed to hypocalcemia exacerbated by potential cerebral edema. The pelvic limb paresis suggested a T3–L3 spinal lesion. Pain management was instituted with fentanyl (2 mcg/kg IV PRN).j Spinal radiographs were suggestive of a compression fracture of the vertebral body of T11, although a congenital deformity could not be ruled out (Fig 3A). Computed tomography confirmed the fracture of T11 and showed accompanying spinal cord compression. Flaring of the ribs at the costochondral junctions (so-called rachitic rosary in people) was also readily apparent on radiographs (Fig 3B). Radiographs of the distal radial and ulnar growth plates, however, showed progressive improvement in mineralization compared with the images taken at 5 months of age (Fig 2C and D). Radiographs at 8.5 months, 3.5 months after initiation of treatment. (A) Lateral radiograph of the spine at the thoracolumbar junction. There is generalized osteopenia, the T11 vertebral body is wedged shaped, and there is concavity of the ventral margin of the vertebral body. These changes are highly suggestive of a pathologic compression fracture, although a preexisting vertebral body anomaly could not be ruled out. (B) Lateral radiograph of the costochondral junctions. The junctions are “flared” and moderately sclerotic. This radiographic finding is frequently present in human patients with rickets, and is commonly called a rachitic rosary, because the lesions palpate like beads on a rosary. Given the severity of the dog's spinal injury (functionally complete), the chance of recovery was very low and would have been compromised by the difficulty in surgical repair of osteopenic bones. As a result, the dog was euthanized. Gross postmortem evaluation revealed signs of rickets with diffusely enlarged costochrondral junctions (beading), a fracture callus on the left eight rib, and displacement of the T11 vertebra. Microscopically, failure of endochondral ossification with retained cartilage cores was noted in several locations (ribs, radius, nasal turbinates). A compression fracture of T11 with subluxation was confirmed. In the region of T11, locally extensive, severe myelomalacia, and fibrinoid vasculitis of the spinal cord were seen. The brain was normal, suggesting that severe hypocalcemia was the cause for the dog's forebrain signs. The parathyroid was diffusely hyperplastic and hypertrophied, consistent with the persistently increased PTH levels. HVDRR in humans is almost always due to mutations in the VDR.2 For this reason, before euthanasia, blood samples were drawn from both the affected dog and the normal half-sibling for genomic sequence analysis of the VDR gene. With owner consent, immediately before euthanasia, the affected dog was anesthetized with propofolk to obtain skin biopsies from her ventral abdomen from which fibroblast cultures were derived. These cultures were subsequently used for analysis of VDR expression and as a source of RNA for VDR sequence analysis. The fibroblasts were grown in minimal essential media containing 10% calf seruml and maintained in an atmosphere of 95% air, 5% CO2 at 37°C. Genomic DNA was isolated from blood using a commercial kit.m Primers were designed based on the DNA sequence of Canis lupus familiaris VDR obtained from GenBank® (accession number NC_006609, Gene ID: 486588) (Table 2). Exons 2–9 of the VDR gene from the affected dog and half-sibling were amplified by PCR and directly sequenced at the Stanford University protein and nucleic acid facility. A unique single base deletion (guanine) was identified at the exon 4-intron junction (Fig 4A) in the affected dog's genomic DNA. The sequence of the exon 4-intron junction of the half-sibling was homozygous for the wild-type sequence (Fig 4B). DNA sequence of exon 4 of the VDR gene in the dog. (A) Genomic DNA sequence of the affected dog's VDR gene. A unique 1 bp (G) deletion was identified in the exon 4-intron junction (B) DNA sequence of the half-sibling's VDR gene. (C) Sequence of the affected dog's VDR cDNA. Deletion of a single guanine nucleotide base was identified in the dog's VDR cDNA resulting in a frameshift that introduced a downstream premature termination codon. The premature stop codon is predicted to be at codon 216, which is 232 amino acids upstream of the normal stop codon. The translated amino acid sequence is shown above the nucleotide sequence. The normal amino acid sequence and that of the affected dog diverge after amino acid R175. From the sequence in GenBank®, the normal VDR exon4-intron sequence is AGG|gtacgtggcc (exon 4 sequence in capitals and intron sequence in lower case with bolded letters indicating splicing recognition sequence). The deletion of a single guanine base in the GG|g triplet would generate the sequence AG|gtacgtggcc and leave the 5′-splice site intact. On the other hand, deletion of guanine in the coding sequence would cause a frameshift in exon 5. In order to document this frameshift, RNA was isolated from the dog's cultured fibroblasts. The RNA was reverse transcribedn and amplifiedo by PCR using gene specific primers (forward primer 5′-ctgcggcccaagctgtcgga and reverse primer 5′-ttggatgctgtaactgaccag). The VDR cDNA products were purifiedp and directly sequenced. As shown in Fig 4C, the single guanine nucleotide deletion in the VDR cDNA led to a frameshift that caused the amino acid sequence to diverge after R175. (It should be noted that the canine R175 corresponds to R154 in humans, because the canine VDR sequence is 21 amino acids longer at the N-terminus compared with the human sequence.) An additional 41 amino acids were in frame before a downstream termination signal occurred. The mutation deleted 273 amino acids of the VDR ligand-binding domain (LBD) and was expected to abolish 1,25(OH)2D3 binding. Although we were able to amplify the VDR cDNA from the dog's cells, the mutant VDR mRNA transcript may be subjected to nonsense-mediated mRNA decay and the affected dog may not express any VDR. To determine whether the mutation abolished 1,25(OH)2D3 binding, we examined [3H]1,25(OH)2D3 binding in the dog's fibroblasts compared with normal human fibroblasts. Cell extracts were incubated with 1 nM [3H]1,25(OH)2D3 (specific activity 158 Ci/mmol) with or without 250-fold excess of radioinert 1,25(OH)2D3 as described previously.3 Hydroxylapatite was used to separate bound and free hormone. Protein concentrations were determined by the Bradford method.4 No detectable binding was observed in extracts from the dog's cells. This report describes a VDR gene mutation resulting in HVDRR in a dog. The molecular basis for HVDRR was attributed to a 1 bp deletion in exon 4 that caused a frameshift and introduced a premature stop in exon 5. We expect that this mutation would lead to the affected dog's failure to respond to 1,25(OH)2D3 in one of 2 ways: either the mutation truncated a major portion of the LBD, leading to the inability of the dog's VDR to bind 1,25(OH)2D3, or the mRNA was subjected to nonsense-mediated degradation and this dog had a complete failure of VDR expression. The absence of 1,25(OH)2D3 binding in the dog fibroblast binding assay confirms that the affected dog's cells lack a VDR capable of responding to 1,25(OH)2D3, although it does not differentiate between these two causes of defective VDR binding. Over 100 human cases of HVDRR have been reported.2 In children, HVDRR is characterized by hypocalcemia, secondary hyperparathyroidism, and severe rickets.5,6 The disease is almost always because of mutations in the VDR, with many different mutations identified, including mutations in the LBD and in the DNA-binding domain.5,6 The VDR mutations result in end-organ resistance to 1,25(OH)2D3.2 Resistance leads to defective intestinal calcium absorption, hypocalcemia, and secondary hyperparathyroidism, which in turn causes failure of bone mineral deposition, especially failure of calcium deposition.5,7 As a result, metaphyseal cartilage accumulates, but cannot be properly mineralized and rickets results.7 A syndrome that is similar to HVDRR has been described in cats,7–9 although a genetic mutation in the VDR was not established in any of these animals. These case reports suggest that cats fare relatively well once they reach the end of their growth period, with the exception of one cat, which died suddenly at 13 months of age, and another that was euthanized at 9 years of age for hip pain from osteoarthritis.7–9 Inadequate dietary intake of vitamin D resulting in nutritional secondary hyperparathyroidism has been reported previously in dogs,10 but could be readily ruled out in this case because the dog failed to respond to high concentrations of calcitriol. VDDR-I has been reported in a Saint Bernard dog and a domestic short hair cat.11,12 In the dog reported here, clinical signs of early onset rickets, laboratory findings of hypocalcemia, secondary hyperparathyroidism, and markedly increased serum 1,25(OH)2D3 levels, and radiographic findings of abnormally wide growth plates are all consistent with those reported in people with HVDRR. The dog's poor response to therapy appears to be closely aligned with the human condition in how challenging it is to maintain normal calcium levels and adequate bone mineralization without functional VDRs. Most mutations in people result in a defective VDR that can no longer respond to even high doses of 1,25(OH)2D3. Some children can be treated by high doses of 1,25(OH)2D3 that overcome the defect in binding affinity for 1,25(OH)2D3, however, treatment usually requires high doses of IV calcium administered daily over many months to eventually correct the hypocalcemia, suppress the secondary hyperparathyroidism, and heal the rachitic bone abnormalities.13,14 IV calcium infusions bypass the intestinal calcium absorption defect caused by the disease. After the total body calcium deficit is restored to normal, some children can be transitioned to high doses of oral calcium to maintain their improved metabolic state and prevent rickets from recurring. It is possible that aggressive initial management of this dog with oral calcium therapy and injectable calcium supplementation may have improved the outcome in this case. Based on the VDR LBD mutation in this dog, she could not have responded to even high concentrations of calcitriol. Evidence that the calcium treatment regime used in this case had some efficacy was shown by the increase in bone mineralization seen in her appendicular skeletal radiographs from 5 to 8.5 months of age (Fig 2). Alternatively, an even more aggressive initial approach with vascular access port placement15 and daily IV calcium supplementation (with concurrent ECG monitoring) could have been undertaken as it is in human patients.16 This approach would be technically challenging, would likely be associated with port infections, and would require significant owner commitment. It is noteworthy that the alopecia observed in this dog is also present in many children with HVDDR.5,6 It is proposed that the product of the hairless gene (HR) acts as a corepressor of the VDR, and that the HR and the unliganded VDR are involved in regulation of the hair cycle.17–22 The details of the mechanism of alopecia in HVDDR remain unknown. Large cystic follicles filled with keratin were seen in this dog on postmortem evaluation along with thin epithelium, and reduced number and size of adnexal structures such as sebaceous and apocrine glands. The dog's secondary hair follicles were smaller than normal. In people with HVDRR, the hair follicles may appear normal on microscopic examination, but hair shafts are absent.5 It is interesting that the alopecia had resolved at the time of the dog's death, yet obvious dermal changes were still microscopically present. In contrast to this dog, alopecia persists in human patients with HVDRR that undergo successful therapy or that show spontaneous improvement in calcium homeostasis.5 In humans, all cases VDR mutations causing premature termination codons have life-long alopecia, even if medical treatment improves the hypocalcemia and rickets. We have no explanation for the improvement of the alopecia in this dog. Dogs may potentially have a compensatory mechanism in the hair cycle lacked by humans that can replace the absent VDR function. In humans, patients with alopecia generally have more severe resistance to 1,25(OH)2D3 than those without alopecia, which would correlate with the severity of this dog's disease.23 HVDRR is an autosomal recessive genetic disorder in humans.5 Unfortunately, the breeder of this dog was not interested in progenitor testing to help establish the pattern of heredity in this family. aAntech Diagnostics, Lake Success, NY bRoxane Laboratories Inc, Columbus, OH cCalcitriol, 100 ng/mL Fixed Oil Solution, compounded, Health Park Pharmacy, Raleigh, NC dIdexx VetTest 8008 Chemistry Analyzer, Idexx Laboratories, Westbrook, ME eDiagnostic Center for Population and Animal Health, Michigan State University, Lansing, MI fCalcium glycerophosphate and calcium lactate, Calphosan, Glenwood, Englewood, NJ gHeartland Assays, Ames, IA hCalcium gluconate 10%, AAP Pharmaceuticals LLC, Schaumburg, IL iMidazolam, Bedford Laboratories, Bedford, OH jFentanyl, Hospira, Lake Forest, IL kPropofol, Teva Pharmaceuticals, North Wales, PA lHyclone, Logan, UT mQIAamp DNA blood mini kit, Qiagen, Valencia, CA nSuperscript first strand CDNA synthesis kit, Invitrogen, Carlsbad, CA oTAQ DNA polymerase, New England Biolabs, Ipswich, MA pQIAquick PCR purification kit This work was supported by NIH grant DK42482 (to DF) and NCSU CVM teaching initiative funds (to DNL).}, number={6}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={LeVine, D. N. and Zhou, Y. and Ghiloni, R. J. and Fields, E. L. and Birkenheuer, A. J. and Gookin, J. L. and Roberston, I. D. and Malloy, P. J. and Feldman, D.}, year={2009}, pages={1278–1283} }
 @article{bissett_stone_malik_norris_o'brien_mansfield_nicholls_griffin_gookin_2009, title={Observed occurrence of Tritrichomonas foetus and other enteric parasites in Australian cattery and shelter cats}, volume={11}, ISSN={["1532-2750"]}, DOI={10.1016/j.jfms.2009.02.001}, abstractNote={Cattery-housed pedigree cats, located mostly within the USA, have the highest reported prevalence of Tritrichomonas foetus (T foetus) to date. This prospective, multi-institutional, cross sectional study examines the occurrence of T foetus and other enteric parasites in cattery-housed and shelter cats within Australia, where T foetus has only recently been identified. Faecal specimens were collected from 134 cats, including 82 cattery-housed pedigree cats and 52 shelter cats. Faecal examinations performed for most cats included concentration techniques, Snap Giardia test, culture in InPouch medium, and polymerase chain reaction (PCR) amplification of T foetus ribosomal ribonucleic acid (rRNA) genes using species-specific primers. Observed occurrence of T foetus, Giardia species, Isospora species and Toxascaris leonina for cattery-housed cats (and catteries) were 0%, 7.4 (13.8)%, 10.9 (22.6)% and 1.6 (3.2)%, respectively. Observed occurrence of T foetus, Giardia species, Isospora species and hookworms for shelter cats were 0%, 11.5%, 9.8% and 4.9%, respectively. These results suggest the prevalence of T foetus in cattery-housed cats is currently much lower in Australia than in the USA, while Isospora and Giardia species infections are common.}, number={10}, journal={JOURNAL OF FELINE MEDICINE AND SURGERY}, author={Bissett, Sally A. and Stone, Maria L. and Malik, Richard and Norris, Jacqueline M. and O'Brien, Carolyn and Mansfield, Caroline S. and Nicholls, Julia M. and Griffin, Alison and Gookin, Jody L.}, year={2009}, month={Oct}, pages={803–807} }
 @inbook{gookin_2009, place={St. Louis, MO}, edition={14th}, title={Tritrichomonas}, ISBN={9781437711523}, booktitle={Kirk's current veterinary therapy. XIV}, publisher={Elsevier Saunders}, author={Gookin, J.L.}, editor={Bonagura, J.D. and Twedt, D.C. and Kirk, R.W.Editors}, year={2009}, pages={509–512} }
 @article{tolbert_gookin_2009, title={Tritrichomonas foetus: A new agent of feline diarrhea}, volume={31}, number={8}, journal={Compendium-Continuing Education for Veterinarians}, author={Tolbert, M. K. and Gookin, J. L.}, year={2009}, pages={374-} }
 @article{stauffer_birkenheuer_levy_marr_gookin_2008, title={Evaluation of four DNA extraction methods for the detection of Tritrichomonas foetus in feline stool specimens by polymerase chain reaction}, volume={20}, ISSN={["1943-4936"]}, DOI={10.1177/104063870802000518}, abstractNote={ Feces are increasingly valued as practical samples for molecular diagnosis of infectious disease. However, extraction of polymerase chain reaction (PCR) quality DNA from fecal samples can be challenging because of coextraction of PCR inhibitors. Because the type and quantity of PCR inhibitors is influenced by diet, endogenous flora, and concurrent disease, it is unlikely that extraction method performance with human feces can be directly extrapolated to that of domestic cats. In the present study, 4 commercially available DNA extraction methods were examined for their influence on the sensitivity of PCR for the detection of Tritrichomonas foetus in feline stool. DNA was extracted from serially diluted feline-origin T. foetus trophozoites in the absence or presence of feline feces. The ZR Fecal DNA kit was identified as affording the greatest analytical sensitivity and reproducibility and was able to detect ≥10 T. foetus organisms per 100 mg feces in 100% of PCR reactions. Further, the identified extraction method could be completed in the shortest time of all kits tested. }, number={5}, journal={JOURNAL OF VETERINARY DIAGNOSTIC INVESTIGATION}, author={Stauffer, Stephen H. and Birkenheuer, Adam J. and Levy, Michael G. and Marr, Henry and Gookin, Jody L.}, year={2008}, month={Sep}, pages={639–641} }
 @article{bissett_gowan_o'brien_stone_gookin_2008, title={Feline diarrhoea associated with Tritrichomonas cf. foetus and Giardia co-infection in an Australian cattery}, volume={86}, ISSN={["1751-0813"]}, DOI={10.1111/j.1751-0813.2008.00356.x}, abstractNote={A 10‐week‐old female Ocicat was presented at a primary care feline veterinary practice for failure to thrive and diarrhoea. Numerous trophozoites, atypical forGiardiasp., were detected on a direct faecal examination, in addition toGiardiacysts. Although the failure to thrive and diarrhoea resolved following treatment for giardiasis, further diagnostic tests performed on faecal specimens from the kitten and 15 other Ocicats from the same cattery, including culture of trophozoites in In Pouch™ medium, PCR testing and molecular sequencing of PCR amplicons, confirmed infection withTritrichomonascf.foetus.This is the first report in Australia of feline trichomoniasis, which appears to be an emerging infectious disease of cats. Pertinent information regarding the clinical features, diagnosis, therapy, and potential source of feline trichomoniasis within Australia are discussed.}, number={11}, journal={AUSTRALIAN VETERINARY JOURNAL}, author={Bissett, S. A. and Gowan, R. A. and O'Brien, C. R. and Stone, M. R. and Gookin, J. L.}, year={2008}, month={Nov}, pages={440–443} }
 @article{gookin_stauffer_stone_2008, title={Induction of arginase II by intestinal epithelium promotes the uptake of L-arginine from the lumen of Cryptosporidium parvum-infected porcine ileum}, volume={47}, ISSN={["0277-2116"]}, DOI={10.1097/MPG.0b013e31816f6c02}, abstractNote={ABSTRACT}, number={4}, journal={JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION}, author={Gookin, Jody L. and Stauffer, Stephen H. and Stone, Maria R.}, year={2008}, month={Oct}, pages={417–427} }
 @article{gookin_foster_coccaro_stauffer_2008, title={Oral Delivery of L-arginine Stimulates Prostaglandin-dependent Secretory Diarrhea in Cryptosporidium parvum–infected Neonatal Piglets}, volume={46}, ISSN={0277-2116}, url={http://dx.doi.org/10.1097/mpg.0b013e31815c0480}, DOI={10.1097/MPG.0b013e31815c0480}, abstractNote={ABSTRACT}, number={2}, journal={Journal of Pediatric Gastroenterology and Nutrition}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Gookin, Jody L and Foster, Derek M and Coccaro, Maria R and Stauffer, Stephen H}, year={2008}, month={Feb}, pages={139–146} }
 @article{gookin_foster_stauffer_stone (coccaro)_2008, title={T1250 Luminal Uptake of L-Arginine By C. Parvum Infected Porcine Ileum Is Promoted By Epithelial Induction of Arginase II and Stimulates Prostaglandin-Dependent Secretory Diarrhea}, volume={134}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(08)62407-5}, DOI={10.1016/S0016-5085(08)62407-5}, number={4}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Gookin, Jody L. and Foster, Derek M. and Stauffer, Stephen H. and Stone (Coccaro), Maria R.}, year={2008}, month={Apr}, pages={A-515-A-516} }
 @article{van itallie_holmes_bridges_gookin_coccaro_proctor_colegio_anderson_2008, title={The density of small tight junction pores varies among cell types and is increased by expression of claudin-2}, volume={121}, ISSN={0021-9533 1477-9137}, url={http://dx.doi.org/10.1242/jcs.021485}, DOI={10.1242/jcs.021485}, abstractNote={Epithelial tight junctions contain size- and charge-selective pores that control the paracellular movement of charged and noncharged solutes. Claudins influence the charge selectivity and electrical resistance of junctions, but there is no direct evidence describing pore composition or whether pore size or density differs among cell types. To characterize paracellular pores independent of influences from charge selectivity, we profiled the `apparent permeabilities' (Papp) of a continuous series of noncharged polyethylene glycols (PEGs) across monolayers of five different epithelial cell lines and porcine ileum. We also characterized Papp of high and low electrical resistance MDCK cell monolayers expressing heterologous claudins. Papp profiling confirms that the paracellular barrier to noncharged solutes can be modeled as two distinct pathways: high-capacity small pores and a size-independent pathway allowing flux of larger solutes. All cell lines and ileum share a pore aperture of radius 4 Å. Using Papp of a PEG of radius 3.5 Å to report the relative pore number provides the novel insight that pore density along the junction varies among cell types and is not necessarily related to electrical resistance. Expression of claudin-2 results in a selective increase in pore number but not size and has no effect on the permeability of PEGs that are larger than the pores; however, neither knockdown of claudin-2 nor overexpression of several other claudins altered either the number of small pores or their size. We speculate that permeability of all small solutes is proportional to pore number but that small electrolytes are subject to further selectivity by the profile of claudins expressed, explaining the dissociation between the Papp for noncharged solutes and electrical resistance. Although claudins are likely to be components of the small pores, other factors might regulate pore number.}, number={3}, journal={Journal of Cell Science}, publisher={The Company of Biologists}, author={Van Itallie, C. M. and Holmes, J. and Bridges, A. and Gookin, J. L. and Coccaro, M. R. and Proctor, W. and Colegio, O. R. and Anderson, J. M.}, year={2008}, month={Jan}, pages={298–305} }
 @article{gookin_stauffer_coccaro_poore_levy_papich_2007, title={Efficacy of tinidazole for treatment of cats experimentally infected with Tritrichomonas foetus}, volume={68}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.68.10.1085}, abstractNote={Abstract}, number={10}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Gookin, Jody L. and Stauffer, Stephen H. and Coccaro, Maria R. and Poore, Matthew F. and Levy, Michael G. and Papich, Mark G.}, year={2007}, month={Oct}, pages={1085–1088} }
 @article{gookin_stauffer_levy_2007, title={Identification of Pentatrichomonas hominis in feline fecal samples by polymerase chain reaction assay}, volume={145}, ISSN={["1873-2550"]}, DOI={10.1016/j.vetpar.2006.10.020}, abstractNote={Pentatrichomonas hominis is considered to be a commensal protozoan of the vertebrate digestive tract. On the basis of light microscopic examination of feces, some investigators presumptively identified P. hominis as a causative agent of feline diarrhea. However, molecular identification of P. hominis infection in the cat has not been reported. Another trichomonad, Tritrichomonas foetus, is recognized as an intestinal pathogen in cats and often presumptively diagnosed on the basis of the presence of trichomonads in diarrheic feces. It is of importance to determine if cats are natural hosts for P. hominis, as the presence of this organism could result in inaccurate assumption of T. foetus infection. In this study, we used a species-specific PCR assay to identify P. hominis 18S rRNA genes in fecal samples collected from a convenience population of cats in which a high prevalence of T. foetus infection had been previously identified (cat show) or suspected (submitted for T. foetus diagnostic testing). The prevalence of T. foetus infection in these samples was 31% and 28.6%, respectively. P. hominis infection was identified by PCR of DNA extracted from feces of five cats (1.9% and 2.1% of fecal samples, respectively). All cats in which P. hominis was identified were also infected with T. foetus. PCR identification of P. hominis infection in the cat should facilitate future studies to determine the pathogenicity of this species and enable differentiation of P. hominis from other known or as-yet unidentified species of trichomonads that may infect cats.}, number={1-2}, journal={VETERINARY PARASITOLOGY}, author={Gookin, Jody L. and Stauffer, Stephen H. and Levy, Michael G.}, year={2007}, month={Apr}, pages={11–15} }
 @article{gookin_stauffer_coccaro_marcotte_levy_2007, title={Optimization of a species-specific polymerase chain reaction assay for identification of Pentatrichomonas hominis in canine fecal specimens}, volume={68}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.68.7.783}, abstractNote={Abstract}, number={7}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Gookin, Jody L. and Stauffer, Stephen H. and Coccaro, Maria R. and Marcotte, Miriam J. and Levy, Michael G.}, year={2007}, month={Jul}, pages={783–787} }
 @article{blikslager_moeser_gookin_jones_odle_2007, title={Restoration of Barrier Function in Injured Intestinal Mucosa}, volume={87}, ISSN={0031-9333 1522-1210}, url={http://dx.doi.org/10.1152/physrev.00012.2006}, DOI={10.1152/physrev.00012.2006}, abstractNote={Mucosal repair is a complex event that immediately follows acute injury induced by ischemia and noxious luminal contents such as bile. In the small intestine, villous contraction is the initial phase of repair and is initiated by myofibroblasts that reside immediately beneath the epithelial basement membrane. Subsequent events include crawling of healthy epithelium adjacent to the wound, referred to as restitution. This is a highly regulated event involving signaling via basement membrane integrins by molecules such as focal adhesion kinase and growth factors. Interestingly, however, ex vivo studies of mammalian small intestine have revealed the importance of closure of the interepithelial tight junctions and the paracellular space. The critical role of tight junction closure is underscored by the prominent contribution of the paracellular space to measures of barrier function such as transepithelial electrical resistance. Additional roles are played by subepithelial cell populations, including neutrophils, related to their role in innate immunity. The net result of reparative mechanisms is remarkably rapid closure of mucosal wounds in mammalian tissues to prevent the onset of sepsis.}, number={2}, journal={Physiological Reviews}, publisher={American Physiological Society}, author={Blikslager, Anthony T. and Moeser, Adam J. and Gookin, Jody L. and Jones, Samuel L. and Odle, Jack}, year={2007}, month={Apr}, pages={545–564} }
 @article{gookin_copple_papich_poore_stauffer_birkenheuer_twedt_levy_2006, title={Efficacy of ronidazole for treatment of feline Tritrichomonas foetus infection}, volume={20}, ISSN={["1939-1676"]}, DOI={10.1892/0891-6640(2006)20[536:EORFTO]2.0.CO;2}, abstractNote={Objectives: To determine the efficacy of ronidazole (RDZ), tinidazole (TDZ), and metronidazole (MDZ) against Tritrichomonas foetus in vitro and of RDZ for treatment of feline naturally occurring or experimentally induced T foetus infection. Animals: A cat naturally infected with T foetus infection and diarrhea. Ten specific-pathogen-free (SPF) kittens. Procedure: RDZ, TDZ, and MDZ were tested for activity against 3 different feline isolates of T foetus in vitro. RDZ then was administered to a naturally infected cat at 10 mg/kg PO q24h for 10 days. SPF kittens were infected orogastrically with feline T foetus and treated with either placebo or RDZ (10 mg/kg PO q12h for 14 days). Cats with relapsing infection or those receiving placebo were treated subsequently with RDZ (either 30 or 50 mg/kg PO q12h for 14 days). Feces were examined for T foetus by direct microscopy, culture, and polymerase chain reaction (PCR) testing weekly. Results: Both RDZ and TDZ killed T foetus at concentrations .0.1 mg/mL in vitro. In the naturally infected cat, RDZ abolished diarrhea and T foetus infection for 85 days after treatment, at which time infection and diarrhea relapsed. Retreatment with RDZ eradicated diarrhea and T foetus infection for over 407 days. In experimentally induced infection, RDZ at 10 mg/kg caused initial improvement, but infection relapsed in all 5 cats 2 to 20 weeks after treatment. At 30 or 50 mg/kg, 10/10 cats were negative for T foetus infection for follow-up durations of 21 to 30 weeks after treatment. Conclusions and Clinical Relevance: Oral administration of RDZ at 30 to 50 mg/kg q12h for 14 days resolved diarrhea and eradicated infection (on the basis of polymerase chain reaction [PCR] testing) in 1 naturally infected cat and 10 experimentally inoculated cats receiving a different isolate of T foetus.}, number={3}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Gookin, Jody L. and Copple, Christina N. and Papich, Mark G. and Poore, Matthew F. and Stauffer, Stephen H. and Birkenheuer, Adam J. and Twedt, David C. and Levy, Michael G.}, year={2006}, pages={536–543} }
 @article{gookin_chiang_allen_armstrong_stauffer_finnegan_murtaugh_2006, title={NF-kappa B-mediated expression of iNOS promotes epithelial defense against infection by Cryptosporidium parvum in neonatal piglets}, volume={290}, ISSN={["1522-1547"]}, DOI={10.1152/ajpgi.00460.2004}, abstractNote={Cryptosporidium sp. parasitizes intestinal epithelium, resulting in enterocyte loss, villous atrophy, and malabsorptive diarrhea. We have shown that mucosal expression of inducible nitric oxide (NO) synthase (iNOS) is increased in infected piglets and that inhibition of iNOS in vitro has no short-term effect on barrier function. NO exerts inhibitory effects on a variety of pathogens; nevertheless, the specific sites of iNOS expression, pathways of iNOS induction, and mechanism of NO action in cryptosporidiosis remain unclear. Using an in vivo model of Cryptosporidium parvum infection, we have examined the location, mechanism of induction, specificity, and consequence of iNOS expression in neonatal piglets. In acute C. parvum infection, iNOS expression predominated in the villous epithelium, was NF-κB dependent, and was not restricted to infected enterocytes. Ongoing treatment of infected piglets with a selective iNOS inhibitor resulted in significant increases in villous epithelial parasitism and oocyst excretion but was not detrimental to maintenance of mucosal barrier function. Intensified parasitism could not be attributed to attenuated fluid loss or changes in epithelial proliferation or replacement rate, inasmuch as iNOS inhibition did not alter severity of diarrhea, piglet hydration, Cl−secretion, or kinetics of bromodeoxyuridine-labeled enterocytes. These findings suggest that induction of iNOS represents a nonspecific response of the epithelium that mediates enterocyte defense against C. parvum infection. iNOS did not contribute to the pathogenic sequelae of C. parvum infection.}, number={1}, journal={AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY}, author={Gookin, JL and Chiang, S and Allen, J and Armstrong, MU and Stauffer, SH and Finnegan, C and Murtaugh, MP}, year={2006}, month={Jan}, pages={G164–G174} }
 @article{zadrozny_stauffer_armstrong_jones_gookin_2006, title={Neutrophils do not mediate the pathophysiological sequelae of Cryptosporidium parvum infection in neonatal piglets}, volume={74}, ISSN={["1098-5522"]}, url={http://europepmc.org/abstract/med/16988224}, DOI={10.1128/IAI.00153-06}, abstractNote={ABSTRACT}, number={10}, journal={INFECTION AND IMMUNITY}, author={Zadrozny, Leah M. and Stauffer, Stephen H. and Armstrong, Martha U. and Jones, Samuel L. and Gookin, Jody L.}, year={2006}, month={Oct}, pages={5497–5505} }
 @inbook{gookin_2006, place={St. Louis, MO}, edition={3rd}, title={Trichomoniasis}, ISBN={9781416036005}, booktitle={Infectious Diseases of the Dog and Cat}, publisher={Saunder/Elsevier}, author={Gookin, J.L.}, editor={Green, C.E.Editor}, year={2006}, pages={740–744} }
 @article{yaeger_gookin_2005, title={Histologic features associated with Tritrichomonas foetus-induced colitis in domestic cats}, volume={42}, ISSN={["1544-2217"]}, DOI={10.1354/vp.42-6-797}, abstractNote={Tritrichomonas foetus is a venereal pathogen of naturally bred cattle. In domestic cats, T. foetus colonizes the colon, resulting in chronic, large-bowel diarrhea. The infection is prevalent among young, densely housed cats, and there is no effective treatment. To the authors' knowledge, the characteristic microscopic lesions of T. foetus infection in naturally infected cats have not been described. The aim of the study reported here was to characterize the histologic changes in the colon of seven cats with T. foetus infection and chronic diarrhea. All cats were 1 year old or younger (mean, 6.7 ± 1.7 months), and a diagnosis of T. foetus infection was made on the basis of direct fecal smear examination (five cats), fecal culture in InPouch™ TF medium (four cats), single-tube nested polymerase chain reaction (PCR) analysis of DNA extracted from feces (two cats), or observation of trichomonads in sections of colon followed by PCR confirmation on DNA extracted from paraffin-embedded tissue (two cats). The presence of colonic trichomonads was the most diagnostic histologic feature. Organisms were identified in all cats, but in only 24 of 43 (56%) sections of colon. Trichomonads were generally present in close proximity to the mucosal surface and less frequently in the lumen of colonic crypts. The presence of colonic trichomonads was consistently associated with mild-to-moderate lymphoplasmacytic and neutrophilic colitis, crypt epithelial cell hypertrophy, hyperplasia and increased mitotic activity, loss of goblet cells, crypt microabscesses, and attenuation of the superficial colonic mucosa. In two of the cats, histologic lesions were more severe and were associated with invasion of trichomonads into the lamina propria and/or deeper layers of the colon.}, number={6}, journal={VETERINARY PATHOLOGY}, author={Yaeger, MJ and Gookin, JL}, year={2005}, month={Nov}, pages={797–804} }
 @article{gookin_allen_chiang_duckett_armstrong_2005, title={Local peroxynitrite formation contributes to early control of Cryptosporidium parvum infection}, volume={73}, ISSN={["0019-9567"]}, DOI={10.1128/IAI.73.7.3929-3936.2005}, abstractNote={ABSTRACT}, number={7}, journal={INFECTION AND IMMUNITY}, author={Gookin, JL and Allen, J and Chiang, S and Duckett, L and Armstrong, MU}, year={2005}, month={Jul}, pages={3929–3936} }
 @article{gookin_birkenheuer_st john_spector_levy_2005, title={Molecular characterization of trichomonads from feces of dogs with diarrhea}, volume={91}, ISSN={["1937-2345"]}, DOI={10.1645/ge-474r.1}, abstractNote={Trichomonads are occasionally observed in the feces of dogs with diarrhea. On the basis of superficial morphological appearance, these infections have been attributed to opportunistic overgrowth of the commensal, Pentatrichomonas hominis. However, molecular characterization of canine trichomonads has never been reported. This study was performed to determine, by means of rRNA gene sequence analysis, the identity of trichomonads observed in feces from dogs with diarrhea. Total DNA was isolated from fecal samples obtained from a 3-mo-old mixed breed dog and litter of German Shepherd puppies having profuse liquid diarrhea containing numerous trichomonads. Total DNA was subject to PCR amplification of partial 18S rRNA gene or 5.8S, ITS1, ITS2, and partial 18S and 28S rRNA genes using species-specific and universal primers, respectively. Products of 642 and 1864 base-pair length were amplified and cloned. On the basis of rRNA gene sequence, the trichomonads observed in the single dog and the litter of puppies shared 100% identity with Tritrichomonas foetus and P. hominis, respectively. The present study is the first to establish the molecular identity of trichomonads infecting dogs with diarrhea. These studies validate the longstanding assumption that canine trichomoniasis may be attributed to P. hominis. Importantly, these studies additionally recognize that canine trichomoniasis may also be caused by infection with T. foetus.}, number={4}, journal={JOURNAL OF PARASITOLOGY}, author={Gookin, JL and Birkenheuer, AJ and St John, V and Spector, M and Levy, MG}, year={2005}, month={Aug}, pages={939–943} }
 @article{pressler_gookin_sykes_wolf_vaden_2005, title={Urinary tract manifestations of protothecosis in dogs}, volume={19}, ISSN={["1939-1676"]}, DOI={10.1892/0891-6640(2005)19<115:UTMOPI>2.0.CO;2}, abstractNote={Records of 13 dogs with systemic infection with Prototheca sp. from 3 veterinary teaching hospitals were reviewed. Acute renal failure secondary to disseminated infection with Prototheca zopfii was diagnosed in 2 dogs. In 1 dog, acute renal failure developed during administration of immunosuppressive drugs for treatment of anterior uveitis. During diagnostic evaluation of this dog, Prototheca sp. organisms were noted in urine sediment and renal biopsy specimens. In the 2nd dog, acute renal failure was diagnosed after treatment for bacterial cystitis. After diagnosis of protothecosis, organisms were successfully isolated by aerobic urine culture. Both dogs with acute renal failure did not respond to conventional medical therapy. In total, Prototheca sp. was noted in urine sediment in 4 of 8 dogs and successfully cultured from urine in 5 of 7 dogs. Four of 5 dogs had organisms noted in the kidneys on histopathologic examination. In all dogs, the species identified was P zopfii. Sensitivity testing of 3 isolates revealed wide differences in in vitro drug resistance. Examination and culture of urine is recommended as a practical method for diagnosis of systemic infection with Prototheca sp.}, number={1}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Pressler, BM and Gookin, JL and Sykes, JE and Wolf, AM and Vaden, SL}, year={2005}, pages={115–119} }
 @article{rhoads_chen_gookin_wu_fu_blikslager_rippe_argenzio_cance_weaver_et al._2004, title={Arginine stimulates intestinal cell migration through a focal adhesion kinase dependent mechanism}, volume={53}, ISSN={0017-5749}, url={http://dx.doi.org/10.1136/gut.2003.027540}, DOI={10.1136/gut.2003.027540}, abstractNote={Background:l-Arginine is a nutritional supplement that may be useful for promoting intestinal repair. Arginine is metabolised by the oxidative deiminase pathway to form nitric oxide (NO) and by the arginase pathway to yield ornithine and polyamines. Aims: To determine if arginine stimulates restitution via activation of NO synthesis and/or polyamine synthesis. Methods: We determined the effects of arginine on cultured intestinal cell migration, NO production, polyamine levels, and activation of focal adhesion kinase, a key mediator of cell migration. Results: Arginine increased the rate of cell migration in a dose dependent biphasic manner, and was additive with bovine serum concentrate (BSC). Arginine and an NO donor activated focal adhesion kinase (a tyrosine kinase which localises to cell matrix contacts and mediates β1 integrin signalling) after wounding. Arginine stimulated cell migration was dependent on focal adhesion kinase (FAK) signalling, as demonstrated using adenovirus mediated transfection with a kinase negative mutant of FAK. Arginine stimulated migration was dependent on NO production and was blocked by NO synthase inhibitors. Arginine dependent migration required synthesis of polyamines but elevating extracellular arginine concentration above 0.4 mM did not enhance cellular polyamine levels. Conclusions: These results showed that l-arginine stimulates cell migration through NO and FAK dependent pathways and that combination therapy with arginine and BSC may enhance intestinal restitution via separate and convergent pathways.}, number={4}, journal={Gut}, publisher={BMJ}, author={Rhoads, J.M. and Chen, W. and Gookin, J. and Wu, G.Y. and Fu, Q. and Blikslager, A.T. and Rippe, R.A. and Argenzio, R.A. and Cance, W.G. and Weaver, E.M. and et al.}, year={2004}, month={Apr}, pages={514–522} }
 @article{gookin_duckett_armstrong_stauffer_finnegan_murtaugh_argenzio_2004, title={Nitric oxide synthase stimulates prostaglandin synthesis and barrier function in C-parvum-infected porcine ileum}, volume={287}, ISSN={["0193-1857"]}, DOI={10.1152/ajpgi.00413.2003}, abstractNote={Cell culture models implicate increased nitric oxide (NO) synthesis as a cause of mucosal hyperpermeability in intestinal epithelial infection. NO may also mediate a multitude of subepithelial events, including activation of cyclooxygenases. We examined whether NO promotes barrier function via prostaglandin synthesis using Cryptosporidium parvum-infected ileal epithelium in residence with an intact submucosa. Expression of NO synthase (NOS) isoforms was examined by real-time RT-PCR of ileal mucosa from control and C. parvum-infected piglets. The isoforms mediating and mechanism of NO action on barrier function were assessed by measuring transepithelial resistance (TER) and eicosanoid synthesis by ileal mucosa mounted in Ussing chambers in the presence of selective and nonselective NOS inhibitors and after rescue with exogenous prostaglandins. C. parvum infection results in induction of mucosal inducible NOS (iNOS), increased synthesis of NO and PGE2, and increased mucosal permeability. Nonselective inhibition of NOS ( NG-nitro-l-arginine methyl ester) inhibited prostaglandin synthesis, resulting in further increases in paracellular permeability. Baseline permeability was restored in the absence of NO by exogenous PGE2. Selective inhibition of iNOS [l- N6-(1-iminoethyl)-l-lysine] accounted for ∼50% of NOS-dependent PGE2synthesis and TER. Using an entire intestinal mucosa, we have demonstrated for the first time that NO serves as a proximal mediator of PGE2synthesis and barrier function in C. parvum infection. Expression of iNOS by infected mucosa was without detriment to overall barrier function and may serve to promote clearance of infected enterocytes.}, number={3}, journal={AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY}, author={Gookin, JL and Duckett, LL and Armstrong, MU and Stauffer, SH and Finnegan, CP and Murtaugh, MP and Argenzio, RA}, year={2004}, month={Sep}, pages={G571–G581} }
 @article{foster_gookin_poore_stebbins_levy_2004, title={Outcome of cats with diarrhea and Tritrichomonas foetus infection}, volume={225}, ISSN={["1943-569X"]}, url={https://doi.org/10.2460/javma.2004.225.888}, DOI={10.2460/javma.2004.225.888}, abstractNote={Abstract}, number={6}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Foster, DM and Gookin, JL and Poore, MF and Stebbins, ME and Levy, MG}, year={2004}, month={Sep}, pages={888–892} }
 @article{gookin_stebbins_hunt_burlone_fulton_hochel_talaat_poore_levy_2004, title={Prevalence of and risk factors for feline Tritichomonas foetus and Giardia infection}, volume={42}, ISSN={["1098-660X"]}, DOI={10.1128/JCM.42.6.2707-2710.2004}, abstractNote={ABSTRACT}, number={6}, journal={JOURNAL OF CLINICAL MICROBIOLOGY}, author={Gookin, JL and Stebbins, ME and Hunt, E and Burlone, K and Fulton, M and Hochel, R and Talaat, M and Poore, M and Levy, MG}, year={2004}, month={Jun}, pages={2707–2710} }
 @article{cole_blikslager_hunt_gookin_argenzio_2003, title={Cyclooxygenase blockade and exogenous glutamine  enhance sodium absorption in infected bovine ileum}, volume={284}, ISSN={0193-1857 1522-1547}, url={http://dx.doi.org/10.1152/ajpgi.00172.2002}, DOI={10.1152/ajpgi.00172.2002}, abstractNote={We have previously shown that prostanoids inhibit electroneutral sodium absorption in Cryptosporidium parvum-infected porcine ileum, whereas glutamine stimulates electroneutral sodium absorption. We postulated that glutamine would stimulate sodium absorption via a cyclooxygenase (COX)-dependent pathway. We tested this hypothesis in C. parvum-infected calves, which are the natural hosts of cryptosporidiosis. Tissues from healthy and infected calves were studied in Ussing chambers and analyzed via immunohistochemistry and Western blots. Treatment of infected tissue with selective COX inhibitors revealed that COX-1 and -2 must be blocked to restore electroneutral sodium absorption, although the transporter involved did not appear to be the expected Na+/H+exchanger 3 isoform. Glutamine addition also stimulated sodium absorption in calf tissue, but although this transport was electroneutral in healthy tissue, sodium absorption was electrogenic in infected tissue and was additive to sodium transport uncovered by COX inhibition. Blockade of both COX isoforms is necessary to release the prostaglandin-mediated inhibition of electroneutral sodium uptake in C. parvum-infected calf ileal tissue, whereas glutamine increases sodium uptake by an electrogenic mechanism in this same tissue.}, number={3}, journal={American Journal of Physiology-Gastrointestinal and Liver Physiology}, publisher={American Physiological Society}, author={Cole, Jeffrey and Blikslager, Anthony and Hunt, Elaine and Gookin, Jody and Argenzio, Robert}, year={2003}, month={Mar}, pages={G516–G524} }
 @article{gookin_galanko_blikslager_argenzio_2003, title={PG-mediated closure of paracellular pathway and not restitution is the primary determinant of barrier recovery in acutely injured porcine ileum}, volume={285}, ISSN={0193-1857 1522-1547}, url={http://dx.doi.org/10.1152/ajpgi.00532.2002}, DOI={10.1152/ajpgi.00532.2002}, abstractNote={ Small bowel epithelium is at the frontline of intestinal barrier function. Restitution is considered to be the major determinant of epithelial repair, because function recovers in parallel with restitution after acute injury. As such, studies of intact mucosa have largely been replaced by migration assays of cultured epithelia. These latter studies fail to account for the simultaneous roles played by villous contraction and paracellular permeability in recovery of barrier function. NSAIDs result in increased intestinal permeability and disease exacerbation in patients with inflammatory bowel disease (IBD). Thus we examined the reparative attributes of endogenous PGs after injury of ileal mucosa by deoxycholate (6 mM) in Ussing chambers. Recovery of transepithelial electrical resistance (TER) from 20-40 Ω·cm2 was abolished by indomethacin (Indo), whereas restitution of 40-100% of the villous surface was unaffected despite concurrent arrest of villous contraction. In the presence of PG, resident crypt and migrating epithelial cells were tightly apposed. In tissues treated with Indo, crypt epithelial cells had dilated intercellular spaces that were accentuated in the migrating epithelium. TER was fully rescued from the effects of Indo by osmotic-driven collapse of the paracellular space, and PG-mediated recovery was significantly impaired by blockade of Cl- secretion. These studies are the first to clearly distinguish the relative contribution of paracellular resistance vs. restitution to acute recovery of epithelial barrier function. Restitution was ineffective in the absence of PG-mediated paracellular space closure. Failure of PG-mediated repair mechanisms may underlie barrier failure resulting from NSAID use in patients with underlying enteropathy. }, number={5}, journal={American Journal of Physiology-Gastrointestinal and Liver Physiology}, publisher={American Physiological Society}, author={Gookin, Jody L. and Galanko, Joseph A. and Blikslager, Anthony T. and Argenzio, Robert A.}, year={2003}, month={Nov}, pages={G967–G979} }
 @article{levy_gookin_poore_birkenheuer_dykstra_litaker_2003, title={Tritrichomonas foetus and not Pentatrichomonas hominis is the etiologic agent of feline trichomonal diarrhea}, volume={89}, ISSN={["1937-2345"]}, DOI={10.1645/0022-3395(2003)089[0099:TFANPH]2.0.CO;2}, abstractNote={Recently, several investigators have reported large-bowel diarrhea in cats associated with intestinal trichomonad parasites. These reports have presumptively identified the flagellates as Pentatrichomonas hominis, an organism putatively capable of infecting the intestinal tracts of a number of mammalian hosts, including cats, dogs, and man. The purpose of the present study was to determine the identity of this recently recognized flagellate by means of rRNA gene sequence analysis; restriction enzyme digest mapping; and light, transmission, and scanning electron microscopy (SEM).}, number={1}, journal={JOURNAL OF PARASITOLOGY}, author={Levy, MG and Gookin, JL and Poore, M and Birkenheuer, AJ and Dykstra, MJ and Litaker, RW}, year={2003}, month={Feb}, pages={99–104} }
 @article{gookin_foster_poore_stebbins_levy_2003, title={Use of a commercially available culture system for diagnosis of Tritrichomonas foetus infection in cats}, volume={222}, url={https://doi.org/10.2460/javma.2003.222.1376}, DOI={10.2460/javma.2003.222.1376}, abstractNote={Abstract}, number={10}, journal={JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Gookin, JL and Foster, DM and Poore, MF and Stebbins, ME and Levy, MG}, year={2003}, month={May}, pages={1376–1379} }
 @article{cole_gookin_gayle_eisemann_argenzio_blikslager_2002, title={Endoscopy via a gastric cannula to monitor the development of ulcers in the pars esophagea in pigs after consumption of a finely ground feed combined with a period of withholding of feed}, volume={63}, ISSN={["0002-9645"]}, DOI={10.2460/ajvr.2002.63.1076}, abstractNote={Abstract}, number={8}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Cole, JT and Gookin, JL and Gayle, JM and Eisemann, JH and Argenzio, RA and Blikslager, AT}, year={2002}, month={Aug}, pages={1076–1082} }
 @misc{gookin_nordone_argenzio_2002, title={Host responses to Cryptosporidium infection}, volume={16}, ISSN={["0891-6640"]}, DOI={10.1892/0891-6640(2002)016<0012:HRTCI>2.3.CO;2}, abstractNote={Journal of Veterinary Internal MedicineVolume 16, Issue 1 p. 12-21 Open Access Host Responses to Cryptosporidium Infection Jody L. Gookin, Corresponding Author Jody L. Gookin Departments of Anatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh, JVC. Department of Anatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606; e-mail: [email protected]Search for more papers by this authorShila K. Nordone, Shila K. Nordone Departments of Microbiology, Parasitology, and Pathology, College of Veterinary Medicine, North Carolina State University, Raleigh, JVC.Search for more papers by this authorRobert A. Argenzio, Robert A. Argenzio Departments of Anatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh, JVC.Search for more papers by this author Jody L. Gookin, Corresponding Author Jody L. Gookin Departments of Anatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh, JVC. Department of Anatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606; e-mail: [email protected]Search for more papers by this authorShila K. Nordone, Shila K. Nordone Departments of Microbiology, Parasitology, and Pathology, College of Veterinary Medicine, North Carolina State University, Raleigh, JVC.Search for more papers by this authorRobert A. Argenzio, Robert A. Argenzio Departments of Anatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh, JVC.Search for more papers by this author First published: 28 June 2008 https://doi.org/10.1111/j.1939-1676.2002.tb01602.xCitations: 24AboutPDF 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 Abstract Cryptosporidium is a clinically and economically important infection whose pathogenic effect begins with colonization of the intestinal epithelium. Despite intensive efforts, a consistently effective therapy for the infection has yet to be identified. Morbidity and mortality results from ongoing loss of absorptive epithelium, which leads to villous atrophy and malabsorption and release of inflammatory mediators that stimulate electrolyte secretion and diarrhea. With further clarification of the mechanisms underlying enterocyte malfunction in Cryptosporidium infection, it should be possible to design rational nutritional and pharmacologic therapies to enhance nutrient and water absorption, promote the clearance of infected enterocytes, and restore normal villus architecture and mucosal barrier function. References 1 Current WL. Cryptosporidiosis. J Am Vet Med Assoc 1985; 187: 1334– 1338. 2 Guerrant RL. Cryptosporidiosis: An emerging, highly infectious threat. Emerg Infect Dis 1997; 3: 51– 57. 3 Division of Child Health and Development. Improving Child Health. IMCI: The Integrated Approach. Geneva , Switzerland : World Health Organization; 1997. 4 MacKenzie WR, Hoxie NJ, Proctor ME. A massive outbreak in Milwaukee of Cryptosporidium infection transmitted through the public water supply. N Engl J Med 1994; 331: 161– 167. 5 National Dairy Heifer Evaluation Project. Dairy Herd Management Practices Focused on Preweaned Heifers, Part 1. Fort Collins , CO : United States Department of Agriculture and Animal and Plant Health Inspection Service; 1993. 6 DxMonitor Animal Health Report. Etiologic Agents Associated with Calf Diarrhea. Fort Collins , CO : United States Department of Agriculture and Animal and Plant Health Inspection Service; 1992. 7 National Dairy Heifer Evaluation Project. Dairy Heifer Morbidity, Mortality, and Health Management Focusing on Preweaned Heifers: April 1991-July 1992. Fort Collins , CO : United States Department of Agriculture and Animal and Plant Health Inspection Service; 1994. 9 Lopez-Velez R, Tarazona R, Garcia Camacho A, et al. Intestinal and extraintestinal cryptosporidiosis in AIDS patients. 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Cryptosporidium parvum is cytopathic for cultured human biliary epithelia via an apoptotic mechanism. Hepatology 1998; 28: 906– 913. 22 Marcial MA, Madara JL. Cryptosporidium: Cellular localization, structural analysis of absorptive cell-parasite membrane-membrane interactions in guinea pigs, and suggestion of protozoan transport by M cells. Gastroenterology 1986; 90: 583– 594. 23 Tzipori S, Widmer G. The biology of Cryptosporidium. Contrib Microbiol 2000; 6: 1– 32. 24 Elliott DA, Clark DP. Cryptosporidium parvum induces host cell actin accumulation at the host-parasite interface. Infect Immun 2000; 68: 2315– 2322. 25 Bonnin A, Lapillonne A, Petrella T, et al. Immunodetection of the microvillus cytoskeleton molecules villin and ezrin in the parasi-tophorous vacuole wall of Cryptosporidium parvum. Eur J Cell Biol 1999; 78: 794– 801. 26 Forney JR, DeWald DB, Yang S, et al. A role for host phos-phoinositide 3-kinase and cytoskeletal remodeling during Cryptosporidium parvum infection. 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Lab Invest 1973; 28: 23– 28. 47 Cho JH, Musch MW, DePaoli AM, et al. Glucocorticoids regulate Na/H exchange expression and activity in region and tissue-specific manner. Am J Physiol 1994; 267: C796– C803. 48 Kandil HM, Gray M, Armstrong M, et al. Interaction between PGE2 and tumor necrosis factor in porcine intestinal inflammation and damage. Gastroenterology 1994; 106: A798. 49 Mead JR, Arrowood MJ, Sidwell RW, et al. Chronic Cryptosporidium parvum infection in congenitally immunodeficient SCID and nude mice. J Infect Dis 1991; 163: 1297– 1304. 50 McDonald V, Deer R, Uni S, et al. Immune responses to Cryptosporidium muris and Cryptosporidium parvum in adult immunocom-petent or immunocompromised (nude and SCID) mice. Infect Immun 1992; 60: 3325– 3331. 51 Kuhls TL, Greenfield RA, Mosier DA, et al. Cryptosporidiosis in adult and neonatal mice with severe combined immunodeficiency. J Comp Pathol 1992; 106: 399– 410. 52 Rohlman VC, Kuhis TL, Mosier DA, et al. Cryptosporidium parvum infection after abrogation of natural killer cell activity in normal and severe combined immunodeficient mice. J Parasitol 1993; 79: 295– 297. 53 Chai J-Y, Guk S-M, Han H-K, et al. Role of intraepithelial lymphocytes in mucosal immune responses of mice experimentally infected with Cryptosporidium parvum. J Parasitol 1999; 85: 234– 239. 54 Culshaw RJ, Bancroft GJ, McDonald V. Gut intraepithelial lymphocytes induce immunity against Cryptosporidium infection through a mechanism involving gamma interferon production. Infect Immun 1997; 65: 3074– 3079. 55 Taghi-Kilani R, Sekla L, Hayglass KT. The role of humoral immunity in Cryptosporidium spp. infection. Studies with B cell-depleted mice. J Immunol 1990; 145: 1571– 1576. 56 Perryman LE, Mason PH, Chrisp CE. Effect of spleen cell populations on resolution of Cryptosporidium parvum infection in SCID mice. Infect Immun 1994; 62: 1474– 1477. 57 Waters WR, Harp JA. Cryptosporidium parvum in T-cell receptor (TCR)-α- and TCR-δ-deficient mice. Infect Immun 1996; 64: 1854– 1857. 58 Aguirre SA, Mason PH, Perryman LE. Susceptibility of major histocompatibility complex (MHC) class I- and MHC class II-deficient mice to Cryptosporidium parvum infection. Infect Immun 1994; 62: 697– 699. 59 McDonald V, Robinson HA, Kelly JP, et al. Immunity to Cryptosporidium muris infection in mice is expressed through gut CD4+ intraepithelial lymphocytes. Infect Immun 1996; 64: 2556– 2562. 60 Wyatt CR, Brackett EJ, Perryman LE, et al. Activation of intestinal intraepithelial T lymphocytes in calves infected with Cryptosporidium parvum. Infect Immun 1997; 65: 185– 190. 61 Wyatt CR, Brackett EJ, Barrett WJ. Accumulation of mucosal T lymphocytes around epithelial cells after in vitro infection with Cryptosporidium parvum. J Parasitol 1999; 85: 765– 768. 62 Adjei AA, Curran BC, Castro M, et al. γδ+ T cells and 65-kDa heat shock protein expression following Cryptosporidium parvum challenge in athymic C57BL/6J nude mice. Immunol Lett 2000; 72: 35– 38. 63 Waters WR, Harp JA, Nonnecke BJ. Phenotypic analysis of peripheral blood lymphocytes and intestinal intra-epithelial lymphocytes in calves. Vet Immunol Immunopathol 1995; 48: 249– 259. 64 Ungar BLP, Kao TC, Burris AA, et al. Cryptosporidium infection in an adult mouse model: Independent roles for IFNγ and CD4+ T lymphocytes in protective immunity. J Immunol 1991; 147: 1014– 1022. 65 Chen W, Harp JA, Harmsen AG. Requirements for CD4+ cells and gamma interferon in resolution of established Cryptosporidium parvum infection in mice. Infect Immun 1993; 61: 3928– 3932. 66 Chen W, Harp JA, Harmsen AG, et al. Gamma interferon functions in resistance to Cryptosporidium parvum infection in severe combined immunodeficient mice. Infect Immun 1993; 61: 3548– 3551. 67 Enriquez FJ, Sterling CR. Role of CD4+ Thl- and Th2-cell secreted cytokines in cryptosporidiosis. Fol Parasitol 1993; 40: 307– 311. 68 Urban JF, Fayer R, Chen SJ, et al. IL-12 protects immunocom-petent and immunodeficient neonatal mice against infection with Cryptosporidium parvum. J Immunol 1996; 156: 263– 268. 69 Aguirre SA, Perryman LE, Davis WC, et al. IL-4 protects adult C57BL/6 mice from prolonged Cryptosporidium parvum infection: Analysis of CD4+αβ+IFN–γ+ and CD4+αβ+IL-4+ lymphocytes in gut-associated lymphoid tissue during resolution of infection. J Immunol 1998; 161: 1891– 1900. 70 Lukin K, Cosyns M, Mitchell T, et al. Eradication of Cryptosporidium parvum infection by mice with ovalbumin-specific T cells. Infect Immun 2000; 68: 2663– 2670. 71 Griffiths JK, Theodos C, Paris M, et al. The gamma interferon gene knockout mouse: A highly sensitive model for evaluation of therapeutic agents against Cryptosporidium parvum. J Clin Microbiol 1998; 36: 2503– 2508. 72 You X, Mead JR. Characterization of experimental Cryptosporidium parvum infection in IFN-γ knockout mice. Parasitology 1998; 117: 525– 531. 73 Colgan SP, Parkos CA, Matthews JB, et al. Interferon-γ induces a cell surface phenotype switch on T84 intestinal epithelial cells. Am J Physiol 1994; 267: C402– C410. 74 Müerköster S, Laman JD, Rocha M, et al. Functional and in situ evidence for nitric oxide production driven by CD40-CD40L interactions in graft-versus-leukemia reactivity. Clin Cancer Res 2000; 6: 1988– 1996. 75 Pollok RC, Farthing MJ, Bajaj-Elliott M, et al. Cellular mechanisms of interferon γ mediated inhibition of Cryptosporidium parvum infection. Gastroenterology 2000; 118: A817. 76 Dignass AU, Podolsky DK, Rachmilewitz D. NOX generation by cultured small intestinal epithelial cells. Dig Dis Sci 1995; 40: 1859– 1865. 77 Foy TM, Aruffo A, Bajorath J, et al. Immune regulation by CD40 and its ligand GP39. Annu Rev Immunol 1996; 14: 591– 617. 78 Leitch GJ, He Q. Reactive nitrogen and oxygen species ameliorate experimental cryptosporidiosis in the neonatal BALB/c mouse model. Infect Immun 1999; 67: 5885– 5891. 79 Leitch GJ, He Q. Arginine-derived nitric oxide reduces fecal oocyst shedding in nude mice infected with Cryptosporidium parvum. Infect Immun 1994; 62: 5173– 5176. 80 Hayward AR, Chmura K, Cosyns M. Interferon-γ is required for innate immunity to Cryptosporidium parvum in mice. J Infect Dis 2000; 182: 1001– 1004. 81 Kuhls TL, Mosier DA, Abrams VL, et al. Inability of interfer-on-gamma and aminoguanidine to alter Cryptosporidium parvum infection in mice with severe combined immunodeficiency. J Parasitol 1994; 80: 480– 485. 82 James SL. Role of nitric oxide in parasitic infections. Microbiol Rev 1995; 59: 533– 547. 83 Eckmann L, Laurent F, Langford TD, et al. Nitric oxide production by human intestinal epithelial cells and competition for argi-nine as potential determinants of host defense against the lumen-dwelling pathogen Giardia lamblia. J Immunol 2000; 164: 1478– 1487. 84 Brune B, von Knethen A, Sandau KB. Nitric oxide and its role in apoptosis. Eur J Pharmacol 1998; 351: 261– 272. 85 Miller MJS, Thompson JH, Zhang X-J, et al. Role of inducible nitric oxide synthase expression and peroxynitrite formation in guinea pig ileitis. Gastroenterology 1995; 109: 1475– 1483. 86 Theodos CM, Sullivan KL, Griffiths JK, et al. Profiles of healing and nonhealing Cryptosporidium parvum infection in C57BL/6 mice with functional B and T lymphocytes: The extent of gamma interferon modulation determines the outcome of infection. Infect Immun 1997; 65: 4761– 4769. 87 Smith LM, Bonafonte MT, Mead JR. Cytokine expression and specific lymphocyte proliferation in two strains of Cryptosporidium parvwm-infected gamma-interferon knockout mice. J Parasitol 2000; 86: 300– 307. 88 Bellamy R. The natural resistance-associated macrophage protein and susceptibility to intracellular pathogens. Microbes Infect 1999; 1: 23– 27. 89 Feng J, Li Y, Hashad M, et al. Bovine natural resistance associated macrophage protein 1 (Nrampl) gene. Genome Res 1996; 6: 956– 964. Citing Literature Volume16, Issue1January 2002Pages 12-21 ReferencesRelatedInformation}, number={1}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Gookin, JL and Nordone, SK and Argenzio, RA}, year={2002}, pages={12–21} }
 @article{gookin_rhoads_argenzio_2002, title={Inducible nitric oxide synthase mediates early epithelial repair of porcine ileum}, volume={283}, ISSN={["1522-1547"]}, DOI={10.1152/ajpgi.00005.2001}, abstractNote={ Reports conflict regarding the effect of nitric oxide (NO) on intestinal epithelium. In chronic injury, NO appears detrimental by combining with reactive oxygen to form potent-free radicals. In contrast, inhibition of NO synthesis after acute injury exacerbates damage and inflammation. Recent studies have disclosed constitutive expression of inducible NO synthase (iNOS) by normal intestinal epithelia, yet little attention has been given to the role of iNOS in acute epithelial repair. We studied the local effects of iNOS on early epithelial repair of porcine ileal mucosa injured by deoxycholate within Ussing chambers. iNOS was constitutively expressed by the villous epithelium, and after deoxycholate injury, iNOS was expressed by injured and detaching enterocytes. Selective inhibition of iNOS abolished increases in NO synthesis and villous reepithelialization after injury. Exogenous l-arginine rescued baseline reepithelialization from NOS inhibitors but was only capable of stimulating additional repair in the presence of serum. These results demonstrate that iNOS-derived NO is a key mediator of early villous reepithelialization following acute mucosal injury. }, number={1}, journal={AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY}, author={Gookin, JL and Rhoads, JM and Argenzio, RA}, year={2002}, month={Jul}, pages={G157–G168} }
 @article{saito_olby_obledo_gookin_2002, title={Muscle cramps in two standard poodles with hypoadrenocorticism}, volume={38}, DOI={10.5326/0380437}, abstractNote={Two standard poodles were evaluated for painful, episodic muscle cramps affecting their thoracic and pelvic limbs. Both dogs had been diagnosed with hypoadrenocorticism and were being treated with fludrocortisone acetate and prednisone when evaluated for muscle cramps. However, the muscle cramping started approximately 1 month prior to the diagnosis of hypoadrenocorticism. Findings on general physical examination included lethargy and dehydration. Neurological examination was normal between episodes. Serum biochemical abnormalities included hyperalbuminemia, azotemia, hyponatremia, hypochloremia, and hyperkalemia. Altering treatment to desoxycorticosterone pivalate resolved the electrolyte abnormalities and the episodes of muscle cramping in both dogs. The authors conclude that hypoadrenocorticism can be associated with episodes of painful muscle cramping in standard poodles.}, number={5}, journal={Journal of the American Animal Hospital Association}, author={Saito, M. and Olby, N. J. and Obledo, L. and Gookin, Jody}, year={2002}, pages={437–443} }
 @article{gookin_birkenheuer_breitschwerdt_levy_2002, title={Single-Tube Nested PCR for Detection of Tritrichomonasfoetus in Feline Feces}, volume={40}, ISSN={0095-1137}, url={http://dx.doi.org/10.1128/jcm.40.11.4126-4130.2002}, DOI={10.1128/JCM.40.11.4126-4130.2002}, abstractNote={ABSTRACT}, number={11}, journal={Journal of Clinical Microbiology}, publisher={American Society for Microbiology}, author={Gookin, J. L. and Birkenheuer, A. J. and Breitschwerdt, E. B. and Levy, M. G.}, year={2002}, month={Nov}, pages={4126–4130} }
 @article{hopwood_papich_gookin_2001, title={Adverse reactions to sulfonamide administration}, volume={3}, journal={Standards of Care in Emergency and Critical Care Medicine}, author={Hopwood, R. and Papich, M. and Gookin, J.L.}, year={2001}, pages={5–12} }
 @article{gookin_levy_law_papich_poore_breitschwerdt_2001, title={Experimental infection of cats with Tritrichomonas foetus}, volume={62}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.2001.62.1690}, DOI={10.2460/ajvr.2001.62.1690}, abstractNote={Abstract}, number={11}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Gookin, Jody L. and Levy, Michael G. and Law, J. Mac and Papich, Mark G. and Poore, Matthew F. and Breitschwerdt, Edward B.}, year={2001}, month={Nov}, pages={1690–1697} }
 @article{levy_gookin_poore_litaker_dykstra_2001, title={Information on parasitic gastrointestinal tract infections in cats (Letter to the Editor)}, volume={218}, number={2}, journal={Journal of the American Veterinary Medical Association}, author={Levy, M.G. and Gookin, J.L. and Poore, M.F. and Litaker, R.W. and Dykstra, M.}, year={2001}, pages={194–195} }
 @article{pappalardo_brown_gookin_morrill_breitschwerdt_2000, title={Granulomatous disease associated with Bartonella infection in 2 dogs}, volume={14}, ISSN={["0891-6640"]}, DOI={10.1892/0891-6640(2000)014<0037:GDAWII>2.3.CO;2}, abstractNote={Shortly after removal of an engorged tick from the left ear, a 4-year-old Greyhound was referred for evaluation of fever and a rapidly enlarging mass in the region of the left submandibular lymph node. Histopathologic evaluation of the lymph node resulted in a diagnosis of severe granulomatous lymphadenitis. An 11-year-old mixed-breed dog was referred for evaluation of a 6-week history of serous nasal discharge. Histologic examination of a surgical biopsy from a nasal mass indicated multifocal granulomatous inflammation with fibrosis. Serum samples obtained from both dogs were reactive by immunofluorescent assay to Bartonella vinsonii subsp. berkhoffii antigens (reciprocal titers of 128). Although Bartonella organisms were not isolated by lysis centrifugation blood culture, Bartonella DNA was amplified from tissue samples obtained from each dog (lymph node biopsy from dog 1 and nasal biopsy from dog 2) using primers that amplify a portion of the 16S rRNA gene followed by Southern blot hybridization using a genus-specific probe. Additionally, restriction fragment length polymorphism (RFLP) analysis of a Bartonella-specific citrate synthase gene product obtained from dog 2 resulted in a restriction pattern identical to B. vinsonii subsp. berkhoffii. This is the 1st report of granulomatous disease in dogs associated with Bartonella infection.}, number={1}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Pappalardo, BL and Brown, T and Gookin, JL and Morrill, CL and Breitschwerdt, EB}, year={2000}, pages={37–42} }
 @inbook{stone_gookin_2000, title={Indications for nephrectomy and nephrotomy}, ISBN={0721655238}, booktitle={Kirk's current veterinary therapy : small animal practice (13th Ed.)}, publisher={Philadelphia, PA : W.B. Saunders}, author={Stone, E. A. and Gookin, J.}, year={2000}, pages={866} }
 @article{gookin_stone_sharp_2000, title={Urinary incontinence on dogs and cats. I. Measurement of urethral pressure. A review / L'incontinenza urinaria nel cane e nel gatto. Parte I -- profilometria della pressione uretrale}, volume={14}, ISBN={0394-3151}, number={2}, journal={Veterinaria}, author={Gookin, J. L. and Stone, E. A. and Sharp, N. J.}, year={2000}, pages={33} }
 @article{gookin_stone_sharp_2000, title={Urinary incontinence on dogs and cats. II. Diagnosis and treatment. A review / L'incontinenza urinaria nel cane e nel gatto. Parte II -- diagnosi e trattamento}, volume={14}, ISBN={0394-3151}, number={2}, journal={Veterinaria}, author={Gookin, J. L. and Stone, E. A. and Sharp, N. J.}, year={2000}, pages={43} }
 @article{gookin_riviere_gilger_papich_1999, title={Acute renal failure in four cats treated with paromomycin}, volume={215}, number={12}, journal={Journal of the American Veterinary Medical Association}, author={Gookin, J. L. and Riviere, J. E. and Gilger, B. C. and Papich, M. G.}, year={1999}, pages={1821–1823} }
 @article{gookin_trepanier_bunch_1999, title={Clinical hypothyroidism associated with trimethoprim- sulfadiazine administration in a dog}, volume={214}, number={7}, journal={Journal of the American Veterinary Medical Association}, author={Gookin, J. L. and Trepanier, L. A. and Bunch, S. E.}, year={1999}, pages={1028–1031} }
 @article{gookin_breitschwerdt_ley_gager_benrud_1999, title={Diarrhea associated with trichomonosis in cats}, volume={215}, number={10}, journal={Journal of the American Veterinary Medical Association}, author={Gookin, J. L. and Breitschwerdt, E. B. and Ley, M. G. and Gager, R. B. and Benrud, J. G.}, year={1999}, pages={1450–1454} }
 @article{gookin_atkins_1999, title={Evaluation of the effect of pleural effusion on central venous pressure in cats}, volume={13}, ISSN={["0891-6640"]}, DOI={10.1892/0891-6640(1999)013<0561:EOTEOP>2.3.CO;2}, abstractNote={This study was undertaken to determine if pleural effusion (PEF) increases central venous pressure (CVP) in cats, to define any relationship between volume of PEF and CVP and to ascertain the significance of CVP alterations in cats having PEF and suspected right heart failure (RHF). CVP was measured from a jugular vein before (CVPpre) and after (CVPpost) bilateral thoracentesis in 9 cats with naturally occurring PEF and under experimental conditions in 3 spontaneously breathing anesthetized cats receiving graded intrathoracic infusion of saline. Volumes of introduced and recovered fluid were recorded. A significant decrease occurred in CVP after thoracentesis in cats with naturally occurring PEF (mean difference, 4.5 cm H2O; range, 0-7.0 cm H2O, P .05) over the range of volumes recovered (range, 95-450 mL or 16.4-90 mL/kg). Five cats had CVPpre suggestive of RHF (range, 8.16-20.4 cm H2O). After thoracentesis, RHF was ruled out in 1 cat (CVPpost, 4.08 cm H2O) and the CVP declined but remained abnormally high (9.52 cm H2O) in 1 cat with a mediastinal mass. In 2 cats with confirmed RHF (CVPpre, 20.4 and 16.3 cm H2O), CVP decreased after thoracentesis but remained abnormally high (CVPpost, 14.96 and 10.88 cm H2O). In 1 cat with noncardiogenic PEF and inadequate removal of fluid, CVPpost (8.16 cm H2O) did not decrease. Experimentally, a positive linear relationship was observed between CVP and volume of PEF. The threshold volume required to increase CVP (17 mL/kg) approximated that suggested by clinical observation (22 mL/kg). PEF increases CVP and can cause abnormally high CVP in the absence of RHF.}, number={6}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Gookin, JL and Atkins, CE}, year={1999}, pages={561–563} }
 @article{kyles_stone_gookin_spaulding_clary_wylie_spodnick_1998, title={Diagnosis and surgical management of obstructive ureteral calculi in cats: 11 cases (1993-1996)}, volume={213}, number={8}, journal={Journal of the American Veterinary Medical Association}, author={Kyles, A. E. and Stone, E. A. and Gookin, J. and Spaulding, K. and Clary, E. M. and Wylie, K. and Spodnick, G.}, year={1998}, pages={1150–1156} }
 @article{gookin_bunch_rush_grindem_1998, title={Evaluation of microcytosis in 18 Shibas}, volume={212}, number={8}, journal={Journal of the American Veterinary Medical Association}, author={Gookin, J. L. and Bunch, S. E. and Rush, L. J. and Grindem, C. B.}, year={1998}, pages={1258–1259} }
 @article{gookin_sellon_mcdorman_geoly_1998, title={Systemic Plasmacytosis and Polyclonal Gammopathy in a Dog}, volume={12}, ISSN={0891-6640 1939-1676}, url={http://dx.doi.org/10.1111/j.1939-1676.1998.tb02152.x}, DOI={10.1111/j.1939-1676.1998.tb02152.x}, abstractNote={Journal of Veterinary Internal MedicineVolume 12, Issue 6 p. 471-474 Open Access Systemic Plasmacytosis and Polyclonal Gammopathy in a Dog Jody L. Gookin, Jody L. Gookin Department of Companion Animal and Special Species Medicine, College of Veterinary Medicine, North Carolina State University, Raleigh, NCSearch for more papers by this authorRanee K. Sellon, Corresponding Author Ranee K. Sellon Department of Companion Animal and Special Species Medicine, College of Veterinary Medicine, North Carolina State University, Raleigh, NC Department of Veterinary Clinical Sciences, Washington State University, Pullman, WA 99164–6610; e-mail: [email protected]Search for more papers by this authorKevin S. McDorman, Kevin S. McDorman Department of Microbiology, Pathology, and Parasitology, College of Veterinary Medicine, North Carolina State University, Raleigh, NCSearch for more papers by this authorFrank J. Geoly, Frank J. Geoly Department of Microbiology, Pathology, and Parasitology, College of Veterinary Medicine, North Carolina State University, Raleigh, NCSearch for more papers by this author Jody L. Gookin, Jody L. Gookin Department of Companion Animal and Special Species Medicine, College of Veterinary Medicine, North Carolina State University, Raleigh, NCSearch for more papers by this authorRanee K. Sellon, Corresponding Author Ranee K. Sellon Department of Companion Animal and Special Species Medicine, College of Veterinary Medicine, North Carolina State University, Raleigh, NC Department of Veterinary Clinical Sciences, Washington State University, Pullman, WA 99164–6610; e-mail: [email protected]Search for more papers by this authorKevin S. McDorman, Kevin S. McDorman Department of Microbiology, Pathology, and Parasitology, College of Veterinary Medicine, North Carolina State University, Raleigh, NCSearch for more papers by this authorFrank J. Geoly, Frank J. Geoly Department of Microbiology, Pathology, and Parasitology, College of Veterinary Medicine, North Carolina State University, Raleigh, NCSearch for more papers by this author First published: 05 February 2008 https://doi.org/10.1111/j.1939-1676.1998.tb02152.xCitations: 1 Dr. Sellon is presently affiliated with the Department of Veterinary Clinical Sciences, Washington State University, Pullman, WA AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL References 1 Edgell CJS. McDonald CC, Graham IB. 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Citing Literature Volume12, Issue6November 1998Pages 471-474 ReferencesRelatedInformation}, number={6}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Gookin, Jody L. and Sellon, Ranee K. and McDorman, Kevin S. and Geoly, Frank J.}, year={1998}, month={Nov}, pages={471–474} }
 @article{gookin_brooks_catalfamo_bunch_munana_1997, title={Factor X deficiency in a cat}, volume={211}, number={5}, journal={Journal of the American Veterinary Medical Association}, author={Gookin, J. L. and Brooks, M. B. and Catalfamo, J. L. and Bunch, S. E. and Munana, K. R.}, year={1997}, pages={576–579} }
 @article{vaden_gookin_trogdon_langston_levine_cowgill_1997, title={Use of carbamylated hemoglobin concentration to differentiate acute from chronic renal failure in dogs}, volume={58}, number={11}, journal={American Journal of Veterinary Research}, author={Vaden, S. L. and Gookin, Jody L. and Trogdon, Maureen M. and Langston, C. E. and Levine, J. and Cowgill, L. D.}, year={1997}, pages={1193–1196} }
 @article{gookin_bunch_1996, title={Detrusor-striated sphincter dyssynergia in a dog}, volume={10}, ISSN={["0891-6640"]}, DOI={10.1111/j.1939-1676.1996.tb02075.x}, abstractNote={Journal of Veterinary Internal MedicineVolume 10, Issue 5 p. 339-344 Open Access Detrusor-Striated Sphincter Dyssynergia in a Dog Jody L Gookin, Jody L Gookin Department of Companion Animal and Special Species Medicine, North Carolina State University, College of Veterinary Medicine, Raleigh, NCSearch for more papers by this authorSusan E. Bunch, Corresponding Author Susan E. Bunch Department of Companion Animal and Special Species Medicine, North Carolina State University, College of Veterinary Medicine, Raleigh, NCDVM, PhD, Department of Companion Animal and Special Species Medicine, North Carolina State University, College of Veterinary Medicine, 4700 Hillsborough St, Raleigh, NC 27606Search for more papers by this author Jody L Gookin, Jody L Gookin Department of Companion Animal and Special Species Medicine, North Carolina State University, College of Veterinary Medicine, Raleigh, NCSearch for more papers by this authorSusan E. Bunch, Corresponding Author Susan E. Bunch Department of Companion Animal and Special Species Medicine, North Carolina State University, College of Veterinary Medicine, Raleigh, NCDVM, PhD, Department of Companion Animal and Special Species Medicine, North Carolina State University, College of Veterinary Medicine, 4700 Hillsborough St, Raleigh, NC 27606Search for more papers by this author First published: September 1996 https://doi.org/10.1111/j.1939-1676.1996.tb02075.xCitations: 9AboutPDF 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 Volume10, Issue5September 1996Pages 339-344 ReferencesRelatedInformation}, number={5}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Gookin, JL and Bunch, SE}, year={1996}, pages={339–344} }
 @article{gookin_stone_spaulding_berry_1996, title={Unilateral nephrectomy in dogs with renal disease: 30 cases (1985-1994)}, volume={208}, number={12}, journal={Journal of the American Veterinary Medical Association}, author={Gookin, J. L. and Stone, E. A. and Spaulding, K. A. and Berry, C. R.}, year={1996}, pages={2020} }
 @article{gookin_stone_sharp_1996, title={Urinary incontinence in dogs and cats. Part I. Urethral pressure profilometry}, volume={18}, number={4}, journal={Compendium on Continuing Education for the Practicing Veterinarian}, author={Gookin, J. L. and Stone, E. A. and Sharp, N. J.}, year={1996}, pages={407} }
 @article{gookin_stone_sharp_1996, title={Urinary incontinence in dogs and cats. Part II. Diagnosis and management}, volume={18}, number={5}, journal={Compendium on Continuing Education for the Practicing Veterinarian}, author={Gookin, J. L. and Stone, E. A. and Sharp, N. J.}, year={1996}, pages={525} }
 @inbook{gookin_sharp_1995, place={Cheltenham, Gloucestershire, UK}, edition={2nd}, title={Urodynamic studies}, ISBN={9780905214313}, booktitle={BSAVA manual of small animal neurology}, publisher={British Small Animal Veterinary Association}, author={Gookin, J.L. and Sharp, N.J.H.}, editor={Wheeler, S.J.Editor}, year={1995}, pages={53–57} }
 @inbook{sharp_gookin_1995, place={Cheltenham, Gloucestershire, UKc}, edition={2nd edition}, title={Visceral and bladder dysfunction; Dysautonomia}, ISBN={9780905214313}, booktitle={BSAVA manual of small animal neurology}, publisher={British Small Animal Veterinary Association}, author={Sharp, N.J.H. and Gookin, J.L.}, editor={Wheeler, S.J.Editor}, year={1995}, pages={179–188} }
 @article{wilson_wyatt_gookin_1989, title={Cranial effects of retinoic acid in the loop-tail (Lp) mutant mouse}, volume={10}, number={1}, journal={Journal of Craniofacial Genetics and Developmental Biology}, author={Wilson, D.B. and Wyatt, D.P. and Gookin, J.L.}, year={1989}, month={Dec}, pages={75–81} }