@article{ngo_lieber_kang_sakamoto_kuczma_plemper_gewirtz_2024, title={Intestinal microbiota programming of alveolar macrophages influences severity of respiratory viral infection}, volume={32}, DOI={10.1016/j.chom.2024.01.002}, abstractNote={<h2>Summary</h2> Susceptibility to respiratory virus infections (RVIs) varies widely across individuals. Because the gut microbiome impacts immune function, we investigated the influence of intestinal microbiota composition on RVI and determined that segmented filamentous bacteria (SFB), naturally acquired or exogenously administered, protected mice against influenza virus (IAV) infection. Such protection, which also applied to respiratory syncytial virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was independent of interferon and adaptive immunity but required basally resident alveolar macrophages (AMs). In SFB-negative mice, AMs were quickly depleted as RVI progressed. In contrast, AMs from SFB-colonized mice were intrinsically altered to resist IAV-induced depletion and inflammatory signaling. Yet, AMs from SFB-colonized mice were not quiescent. Rather, they directly disabled IAV via enhanced complement production and phagocytosis. Accordingly, transfer of SFB-transformed AMs into SFB-free hosts recapitulated SFB-mediated protection against IAV. These findings uncover complex interactions that mechanistically link the intestinal microbiota with AM functionality and RVI severity.}, number={3}, journal={Cell Host and Microbe}, publisher={Elsevier BV}, author={Ngo, VL and Lieber, CM and Kang, H-J and Sakamoto, K and Kuczma, M and Plemper, RK and Gewirtz, AT}, year={2024}, month={Mar}, pages={335–348.e8} }
 @article{cox_wolf_lieberman_lieber_kang_sticher_yoon_andrews_govindarajan_krueger_et al._2024, title={Therapeutic mitigation of measles-like immune amnesia and exacerbated disease after prior respiratory virus infections in ferrets}, volume={15}, DOI={10.1038/s41467-024-45418-5}, abstractNote={Abstract Measles cases have surged pre-COVID-19 and the pandemic has aggravated the problem. Most measles-associated morbidity and mortality arises from destruction of pre-existing immune memory by measles virus (MeV), a paramyxovirus of the morbillivirus genus. Therapeutic measles vaccination lacks efficacy, but little is known about preserving immune memory through antivirals and the effect of respiratory disease history on measles severity. We use a canine distemper virus (CDV)-ferret model as surrogate for measles and employ an orally efficacious paramyxovirus polymerase inhibitor to address these questions. A receptor tropism-intact recombinant CDV with low lethality reveals an 8-day advantage of antiviral treatment versus therapeutic vaccination in maintaining immune memory. Infection of female ferrets with influenza A virus (IAV) A/CA/07/2009 (H1N1) or respiratory syncytial virus (RSV) four weeks pre-CDV causes fatal hemorrhagic pneumonia with lung onslaught by commensal bacteria. RNAseq identifies CDV-induced overexpression of trefoil factor (TFF) peptides in the respiratory tract, which is absent in animals pre-infected with IAV. Severe outcomes of consecutive IAV/CDV infections are mitigated by oral antivirals even when initiated late. These findings validate the morbillivirus immune amnesia hypothesis, define measles treatment paradigms, and identify priming of the TFF axis through prior respiratory infections as risk factor for exacerbated morbillivirus disease.}, number={1}, journal={Nature Communications}, publisher={Springer Science and Business Media LLC}, author={Cox, RM and Wolf, JD and Lieberman, NA and Lieber, CM and Kang, H-J and Sticher, ZM and Yoon, J-J and Andrews, MK and Govindarajan, M and Krueger, RE and et al.}, year={2024}, month={Feb} }
 @article{lieber_aggarwal_yoon_cox_kang_sourimant_toots_johnson_jones_sticher_et al._2023, title={4’-Fluorouridine mitigates lethal infection with pandemic human and highly pathogenic avian influenza viruses}, volume={19}, DOI={10.1371/journal.ppat.1011342}, abstractNote={Influenza outbreaks are associated with substantial morbidity, mortality and economic burden. Next generation antivirals are needed to treat seasonal infections and prepare against zoonotic spillover of avian influenza viruses with pandemic potential. Having previously identified oral efficacy of the nucleoside analog 4’-Fluorouridine (4’-FlU, EIDD-2749) against SARS-CoV-2 and respiratory syncytial virus (RSV), we explored activity of the compound against seasonal and highly pathogenic influenza (HPAI) viruses in cell culture, human airway epithelium (HAE) models, and/or two animal models, ferrets and mice, that assess IAV transmission and lethal viral pneumonia, respectively. 4’-FlU inhibited a panel of relevant influenza A and B viruses with nanomolar to sub-micromolar potency in HAE cells. In vitro polymerase assays revealed immediate chain termination of IAV polymerase after 4’-FlU incorporation, in contrast to delayed chain termination of SARS-CoV-2 and RSV polymerase. Once-daily oral treatment of ferrets with 2 mg/kg 4’-FlU initiated 12 hours after infection rapidly stopped virus shedding and prevented transmission to untreated sentinels. Treatment of mice infected with a lethal inoculum of pandemic A/CA/07/2009 (H1N1)pdm09 (pdmCa09) with 4’-FlU alleviated pneumonia. Three doses mediated complete survival when treatment was initiated up to 60 hours after infection, indicating a broad time window for effective intervention. Therapeutic oral 4’-FlU ensured survival of animals infected with HPAI A/VN/12/2003 (H5N1) and of immunocompromised mice infected with pdmCa09. Recoverees were protected against homologous reinfection. This study defines the mechanistic foundation for high sensitivity of influenza viruses to 4’-FlU and supports 4’-FlU as developmental candidate for the treatment of seasonal and pandemic influenza.}, number={4}, journal={PLoS Pathogens}, publisher={Public Library of Science (PLoS)}, author={Lieber, CM and Aggarwal, M and Yoon, J-J and Cox, RM and Kang, H-J and Sourimant, J and Toots, M and Johnson, SK and Jones, CA and Sticher, ZM and et al.}, editor={Schnell, MJEditor}, year={2023}, month={Apr}, pages={e1011342–e1011342} }
 @article{gupta_sarr_fantone_ashtiwi_sakamoto_quinn_rada_2023, title={Dual oxidase 1 is dispensable during Mycobacterium tuberculosis infection in mice}, volume={14}, DOI={10.3389/fimmu.2023.1044703}, abstractNote={Introduction Mycobacterium tuberculosis (Mtb) is the primary cause of human tuberculosis (TB) and is currently the second most common cause of death due to a singleinfectious agent. The first line of defense against airborne pathogens, including Mtb, is the respiratory epithelium. One of the innate defenses used by respiratory epithelial cells to prevent microbial infection is an oxidative antimicrobial system consisting of the proteins, lactoperoxidase (LPO) and Dual oxidase 1 (Duox1), the thiocyanate anion (SCN-) and hydrogen peroxide (H2O2), which together lead to the generation of antimicrobial hypothiocyanite (OSCN-) in the airway lumen. OSCN- kills bacteria and viruses in vitro, but the role of this Duox1-based system in bacterial infections in vivo remains largely unknown. The goal of this study was to assess whether Duox1 contributes to the immune response against the unique respiratory pathogen, Mtb. Methods Duox1-deficient (Duox1 KO) and wild-type (WT) mice were infected with Mtb aerosols and bacterial titers, lung pathology, cytokines and immune cell recruitment were assessed. Results and discussion Mtb titers in the lung, spleen and liver were not different 30 days after infection between WT and Duox1 KO mice. Duox1 did not affect lung histology assessed at days 0, 30, and 90 post-Mtb infection. Mtb-infected Duox1 KO animals exhibited enhanced production of certain cytokines and chemokines in the airway; however, this response was not associated with significantly higher numbers of macrophages or neutrophils in the lung. B cell numbers were lower, while apoptosis was higher in the pulmonary lesions of Mtb-infected Duox1 KO mice compared to infected WT animals. Taken together, these data demonstrate that while Duox1 might influence leukocyte recruitment to inflammatory cell aggregates, Duox1 is dispensable for the overall clinical course of Mtb lung infection in a mouse model.}, journal={Frontiers in Immunology}, publisher={Frontiers Media SA}, author={Gupta, T and Sarr, D and Fantone, K and Ashtiwi, NM and Sakamoto, K and Quinn, FD and Rada, B}, year={2023}, month={Mar} }
 @article{moorhead_evans_sakamoto_dzimianski_mansour_dicosty_fricks_mccall_carson_nelson_et al., title={Effects of doxycycline dose rate and pre-adulticide wait period on heartworm-associated pathology and adult worm mass}, volume={16}, DOI={10.1186/s13071-023-05858-2}, abstractNote={The American Heartworm Society canine guidelines recommend treatment with doxycycline prior to adulticide administration to reduce levels of Wolbachia and its associated metabolites, which are known to be a leading cause of pulmonary pathology. Studies have determined that doxycycline administered at 10 mg/kg BID for 28 days is an effective dose for eliminating Wolbachia, but what has not been determined is the clinical relevance of this elimination. The current guidelines also recommend a 30-day wait period following administration of doxycycline to allow for clearance of metabolites, such as Wolbachia surface protein, and for further reduction in heartworm biomass before administration of adulticide. Reducing the doxycycline dose and eliminating the wait period may carry practical benefits for the animal, client, and practitioner.To investigate these treatment practices, Dirofilaria immitis adults were surgically transplanted into each of 45 dogs, which were divided into nine study groups of five dogs each. Seventy-five days after transplantation, two groups each were administered 5, 7.5, or 10 mg/kg BID doxycycline orally for 28 days and 6 µg/kg ivermectin monthly, with three untreated groups serving as controls. Study animals were necropsied and examined prior to treatment as well as 30 and 60 days post-treatment.Mean worm weight was unaffected by dosage but exhibited a significant increase at 30 days and significant decrease at 60 days post-treatment, including in control groups. Histopathology lesion scores did not significantly differ among groups, with the exception of the lung composite score for one untreated group. Liver enzymes, the levels of which are a concern in doxycycline treatment, were also examined, with no abnormalities in alanine aminotransferase or alkaline phosphatase observed.No consistent worsening of tissue lesions was observed with or without the AHS-recommended 30-day wait period, nor did reduced dosages of doxycycline lead to worsening of pathology or any change in efficacy in depleting worm weight. Mean worm weight did significantly increase prior to, and decrease following, the wait period. Future work that also includes adulticide treatment (i.e. melarsomine) will study treatment recommendations that may improve both animal health and owner compliance.}, number={1}, journal={Parasites and Vectors}, publisher={Springer Science and Business Media LLC}, author={Moorhead, AR and Evans, CC and Sakamoto, K and Dzimianski, MT and Mansour, A and DiCosty, U and Fricks, C and McCall, S and Carson, B and Nelson, CT and et al.} }
 @article{lakin_tavalire_sakamoto_buss_miller_budischak_raum_ezenwa_beechler_jolles_2022, title={Bovine tuberculosis in African buffalo (Syncerus caffer): Progression of pathology during infection}, volume={16}, DOI={10.1371/journal.pntd.0010906}, abstractNote={Bovine tuberculosis (BTB) is a zoonotic disease of global importance endemic in African buffalo (Syncerus caffer) in sub-Saharan Africa. Zoonotic tuberculosis is a disease of global importance, accounting for over 12,000 deaths annually. Cattle affected with BTB have been proposed as a model for the study of human tuberculosis, more closely resembling the localization and progression of lesions in controlled studies than murine models. If disease in African buffalo progresses similarly to experimentally infected cattle, they may serve as a model, both for human tuberculosis and cattle BTB, in a natural environment.We utilized a herd of African buffalo that were captured, fitted with radio collars, and tested for BTB twice annually during a 4-year-cohort study. At the end of the project, BTB positive buffalo were culled, and necropsies performed. Here we describe the pathologic progression of BTB over time in African buffalo, utilizing gross and histological methods. We found that BTB in buffalo follows a pattern of infection like that seen in experimental studies of cattle. BTB localizes to the lymph nodes of the respiratory tract first, beginning with the retropharyngeal and tracheobronchial lymph nodes, gradually increasing in lymph nodes affected over time. At 36 months, rate of spread to additional lymph nodes sharply increases. The lung lesions follow a similar pattern, progressing slowly, then accelerating their progression at 36 months post infection. Lastly, a genetic marker that correlated to risk of M. bovis infection in previous studies was marginally associated with BTB progression. Buffalo with at least one risk allele at this locus tended to progress faster, with more lung necrosis.The progression of disease in the African buffalo mirrors the progression found in experimental cattle models, offering insight into BTB and the interaction with its host in the context of naturally varying environments, host, and pathogen populations.}, number={11}, journal={PLoS Neglected Tropical Diseases}, publisher={Public Library of Science (PLoS)}, author={Lakin, HA and Tavalire, H and Sakamoto, K and Buss, P and Miller, M and Budischak, SA and Raum, K and Ezenwa, VO and Beechler, B and Jolles, A}, editor={Shao, J-WEditor}, year={2022}, month={Nov}, pages={e0010906–e0010906} }
 @article{shey-njila_hikal_gupta_sakamoto_yahyaoui azami_watford_quinn_karls_2022, title={CtpB Facilitates Mycobacterium tuberculosis Growth in Copper-Limited Niches}, volume={23}, DOI={10.3390/ijms23105713}, abstractNote={Copper is required for aerobic respiration by Mycobacterium tuberculosis and its human host, but this essential element is toxic in abundance. Copper nutritional immunity refers to host processes that modulate levels of free copper to alternately starve and intoxicate invading microbes. Bacteria engulfed by macrophages are initially contained within copper-limited phagosomes, which fuse with ATP7A vesicles that pump in toxic levels of copper. In this report, we examine how CtpB, a P-type ATPase in M. tuberculosis, aids in response to nutritional immunity. In vitro, the induced expression of ctpB in copper-replete medium inhibited mycobacterial growth, while deletion of the gene impaired growth only in copper-starved medium and within copper-limited host cells, suggesting a role for CtpB in copper acquisition or export to the copper-dependent respiration supercomplex. Unexpectedly, the absence of ctpB resulted in hypervirulence in the DBA/2 mouse infection model. As ctpB null strains exhibit diminished growth only in copper-starved conditions, reduced copper transport may have enabled the mutant to acquire a "Goldilocks" amount of the metal during transit through copper-intoxicating environments within this model system. This work reveals CtpB as a component of the M. tuberculosis toolkit to counter host nutritional immunity and underscores the importance of elucidating copper-uptake mechanisms in pathogenic mycobacteria.}, number={10}, journal={International Journal of Molecular Sciences}, publisher={MDPI AG}, author={Shey-Njila, O and Hikal, AF and Gupta, T and Sakamoto, K and Yahyaoui Azami, H and Watford, WT and Quinn, FD and Karls, RK}, year={2022}, month={May}, pages={5713–5713} }
 @article{gupta_somanna_rowe_lagatta_helms_owino_jelesijevic_harvey_jacobs_voss_et al._2022, title={Ferrets as a model for tuberculosis transmission}, volume={12}, DOI={10.3389/fcimb.2022.873416}, abstractNote={Even with the COVID-19 pandemic, tuberculosis remains a leading cause of human death due to a single infectious agent. Until successfully treated, infected individuals may continue to transmit Mycobacterium tuberculosis bacilli to contacts. As with other respiratory pathogens, such as SARS-CoV-2, modeling the process of person-to-person transmission will inform efforts to develop vaccines and therapies that specifically impede disease transmission. The ferret (Mustela furo), a relatively inexpensive, small animal has been successfully employed to model transmissibility, pathogenicity, and tropism of influenza and other respiratory disease agents. Ferrets can become naturally infected with Mycobacterium bovis and are closely related to badgers, well known in Great Britain and elsewhere as a natural transmission vehicle for bovine tuberculosis. Herein, we report results of a study demonstrating that within 7 weeks of intratracheal infection with a high dose (>5 x 103 CFU) of M. tuberculosis bacilli, ferrets develop clinical signs and pathological features similar to acute disease reported in larger animals, and ferrets infected with very-high doses (>5 x 104 CFU) develop severe signs within two to four weeks, with loss of body weight as high as 30%. Natural transmission of this pathogen was also examined. Acutely-infected ferrets transmitted M. tuberculosis bacilli to co-housed naïve sentinels; most of the sentinels tested positive for M. tuberculosis in nasal washes, while several developed variable disease symptomologies similar to those reported for humans exposed to an active tuberculosis patient in a closed setting. Transmission was more efficient when the transmitting animal had a well-established acute infection. The findings support further assessment of this model system for tuberculosis transmission including the testing of prevention measures and vaccine efficacy.}, journal={Frontiers in Cellular and Infection Microbiology}, publisher={Frontiers Media SA}, author={Gupta, T and Somanna, N and Rowe, T and LaGatta, M and Helms, S and Owino, SO and Jelesijevic, T and Harvey, S and Jacobs, W and Voss, T and et al.}, year={2022}, month={Aug} }
 @article{wyatt_sarr_sakamoto_watford_2022, title={Influenza-induced Tpl2 expression within alveolar epithelial cells is dispensable for host viral control and anti-viral immunity}, volume={17}, DOI={10.1371/journal.pone.0262832}, abstractNote={Tumor progression locus 2 (Tpl2) is a serine/threonine kinase that regulates the expression of inflammatory mediators in response to Toll-like receptors (TLR) and cytokine receptors. Global ablation of Tpl2 leads to severe disease in response to influenza A virus (IAV) infection, characterized by respiratory distress, and studies in bone marrow chimeric mice implicated Tpl2 in non-hematopoietic cells. Lung epithelial cells are primary targets and replicative niches of influenza viruses; however, the specific regulation of antiviral responses by Tpl2 within lung epithelial cells has not been investigated. Herein, we show that Tpl2 is basally expressed in primary airway epithelial cells and that its expression increases in both type I and type II airway epithelial cells (AECI and AECII) in response to influenza infection. We used Nkx2.1-cre to drive Tpl2 deletion within pulmonary epithelial cells to delineate epithelial cell-specific functions of Tpl2 during influenza infection in mice. Although modest increases in morbidity and mortality were attributed to cre-dependent deletion in lung epithelial cells, no alterations in host cytokine production or lung pathology were observed. In vitro, Tpl2 inhibition within the type I airway epithelial cell line, LET1, as well as genetic ablation in primary airway epithelial cells did not alter cytokine production. Overall, these findings establish that Tpl2-dependent defects in cells other than AECs are primarily responsible for the morbidity and mortality seen in influenza-infected mice with global Tpl2 ablation.}, number={1}, journal={PLoS ONE}, publisher={Public Library of Science (PLoS)}, author={Wyatt, KD and Sarr, D and Sakamoto, K and Watford, WT}, editor={Bose, SEditor}, year={2022}, month={Jan}, pages={e0262832–e0262832} }
 @article{tolbert_weyna_sakamoto_perlini_platt_2022, title={Magnetic resonance imaging and pathological characteristics of <i>Cladophialophora</i> encephalitis in a young dog}, volume={11}, ISSN={2052-6121 2052-6121}, url={http://dx.doi.org/10.1002/vrc2.520}, DOI={10.1002/vrc2.520}, abstractNote={Abstract A 1‐year‐old dog was presented for persistent neck pain and circling. Magnetic resonance imaging revealed a large, space‐occupying, intra‐axial mass with extensive surrounding vasogenic oedema affecting the left thalamus and hippocampus. Postmortem histopathology of the brain lesion identified fungal hyphae with significant local brain reaction. Fungal sequencing confirmed Cladophialophora bantiana . Magnetic resonance imaging findings can look similar to other inflammatory processes or even neoplasia. While histopathology of the lesions may not always identify fungal hyphae, it will often confirm necrosis, pyogranulomatous inflammation and perivascular cuffing with lymphocytes. Cerebral phaeohyphomycosis should be included in the differential diagnosis list in a young dog with intracranial neurologic deficits.}, number={1}, journal={Veterinary Record Case Reports}, publisher={Wiley}, author={Tolbert, Alexis and Weyna, Alisia and Sakamoto, Kaori and Perlini, Michael and Platt, Simon}, year={2022}, month={Oct} }
 @article{sourimant_lieber_yoon_toots_govindarajan_udumula_sakamoto_natchus_patti_vernachio_et al._2022, title={Orally efficacious lead of the AVG inhibitor series targeting a dynamic interface in the respiratory syncytial virus polymerase}, volume={8}, url={https://doi.org/10.1126/sciadv.abo2236}, DOI={10.1126/sciadv.abo2236}, abstractNote={Respiratory syncytial virus (RSV) is a leading cause of lower respiratory infections in infants and the immunocompromised, yet no efficient therapeutic exists. We have identified the AVG class of allosteric inhibitors of RSV RNA synthesis. Here, we demonstrate through biolayer interferometry and in vitro RNA-dependent RNA polymerase (RdRP) assays that AVG compounds bind to the viral polymerase, stalling the polymerase in initiation conformation. Resistance profiling revealed a unique escape pattern, suggesting a discrete docking pose. Affinity mapping using photoreactive AVG analogs identified the interface of polymerase core, capping, and connector domains as a molecular target site. A first-generation lead showed nanomolar potency against RSV in human airway epithelium organoids but lacked in vivo efficacy. Docking pose-informed synthetic optimization generated orally efficacious AVG-388, which showed potent efficacy in the RSV mouse model when administered therapeutically. This study maps a druggable target in the RSV RdRP and establishes clinical potential of the AVG chemotype against RSV disease.}, number={25}, journal={Science Advances}, publisher={American Association for the Advancement of Science (AAAS)}, author={Sourimant, Julien and Lieber, Carolin M. and Yoon, Jeong-Joong and Toots, Mart and Govindarajan, Mugunthan and Udumula, Venkata and Sakamoto, Kaori and Natchus, Michael G. and Patti, Joseph and Vernachio, John and et al.}, year={2022}, month={Jun} }
 @inproceedings{filipov_mote_sakamoto_gupta_wallon_carpenter_2022, title={P16-02 Mycobacterium tuberculosis challenge enhances dopaminergic toxicity and neuroinflammation caused by intrapallidal manganese administration}, volume={368}, DOI={10.1016/j.toxlet.2022.07.592}, booktitle={Toxicology Letters}, publisher={Elsevier BV}, author={Filipov, NM and Mote, RS and Sakamoto, K and Gupta, T and Wallon, OK and Carpenter, JM}, year={2022}, month={Sep}, pages={S218–S219} }
 @misc{dzimianski_sakamoto_moorhead_2022, title={Replacing the dog in canine heartworm research. I. Description of a novel in vivo model.}, author={Dzimianski, M and Sakamoto, K and Moorhead, A}, year={2022}, month={Sep} }
 @article{lieber_cox_sourimant_wolf_juergens_phung_saindane_smith_sticher_kalykhalov_et al._2022, title={SARS-CoV-2 VOC type and biological sex affect molnupiravir efficacy in severe COVID-19 dwarf hamster model}, volume={13}, DOI={10.1038/s41467-022-32045-1}, abstractNote={Abstract SARS-CoV-2 variants of concern (VOC) have triggered infection waves. Oral antivirals such as molnupiravir promise to improve disease management, but efficacy against VOC delta was questioned and potency against omicron is unknown. This study evaluates molnupiravir against VOC in human airway epithelium organoids, ferrets, and a lethal Roborovski dwarf hamster model of severe COVID-19-like lung injury. VOC were equally inhibited by molnupiravir in cells and organoids. Treatment reduced shedding in ferrets and prevented transmission. Pathogenicity in dwarf hamsters was VOC-dependent and highest for delta, gamma, and omicron. All molnupiravir-treated dwarf hamsters survived, showing reduction in lung virus load from one (delta) to four (gamma) orders of magnitude. Treatment effect size varied in individual dwarf hamsters infected with omicron and was significant in males, but not females. The dwarf hamster model recapitulates mixed efficacy of molnupiravir in human trials and alerts that benefit must be reassessed in vivo as VOC evolve.}, number={1}, journal={Nature Communications}, publisher={Springer Science and Business Media LLC}, author={Lieber, CM and Cox, RM and Sourimant, J and Wolf, JD and Juergens, K and Phung, Q and Saindane, MT and Smith, MK and Sticher, ZM and Kalykhalov, AA and et al.}, year={2022}, month={Jul} }
 @inproceedings{campbell_dzimianski_evans_sakamoto_moorhead_2022, title={The cellular immune response to infection by Dirofilaria immitis in the peritoneal cavity and peritoneal wall of the Mongolian gerbil (Meriones unguiculatus)}, author={Campbell, E and Dzimianski, M and Evans, C and Sakamoto, K and Moorhead, A}, year={2022}, month={Sep} }
 @inproceedings{campbell_dzimianski_evans_sakamoto_moorhead_2022, title={The cellular immune response to infection by Dirofilaria immitis larvae in the peritoneal cavity and peritoneal wall of the Mongolian gerbil (Meriones unguiculatus)}, author={Campbell, E and Dzimianski, M and Evans, C and Sakamoto, K and Moorhead, A}, year={2022}, month={Jun} }
 @inproceedings{chu_dzimianski_evans_pulaski_sakamoto_moorhead_2022, title={The in vitro molting of Wolbachia-depleted Dirofilaria immitis from third-stage larvae to fourth-stage larvae}, author={Chu, Y and Dzimianski, M and Evans, C and Pulaski, C and Sakamoto, K and Moorhead, A}, year={2022}, month={Sep} }
 @article{latha_rao_sakamoto_watford_2022, title={Tumor Progression Locus 2 Protects against Acute Respiratory Distress Syndrome in Influenza A Virus-Infected Mice}, volume={10}, DOI={10.1128/spectrum.01136-22}, abstractNote={This study demonstrates the protective role of the serine-threonine mitogen-activated protein kinase, Tpl2, in influenza virus pathogenesis and reveals that host Tpl2 deficiency is sufficient to convert a low-pathogenicity influenza A virus infection into severe influenza disease that resembles ARDS, both histopathologically and transcriptionally. The IAV-infected Tpl2 −/− mouse thereby represents a novel murine model for studying ARDS-like disease that could improve our understanding of this aggressive disease and assist in the design of better diagnostics and treatments.}, number={5}, journal={Microbiology spectrum}, publisher={American Society for Microbiology}, author={Latha, K and Rao, S and Sakamoto, K and Watford, WT}, editor={Ramage, HEditor}, year={2022}, month={Oct} }
 @article{kirejczyk_goodwin_gyimesi_zachariah_sturgeon_armwood_frontera-acevedo_kokosinksa_seguel_fogelson_et al._2021, title={A Retrospective Study of Pathology in Bats Submitted to an Exotic and Zoo Animal Diagnostic Service in Georgia, USA (2008–2019)}, volume={185}, url={https://doi.org/10.1016/j.jcpa.2021.04.010}, DOI={10.1016/j.jcpa.2021.04.010}, abstractNote={Pathology records of bats submitted to the University of Georgia from managed care settings were reviewed to identify naturally occurring diseases. Fifty-nine cases were evaluated during an 11-year period (2008–2019), including representatives from four families: Pteropodidae (Yinpterochiroptera), Phyllostomidae, Vespertilionidae and Molossidae (Yangochiroptera). Pathology reports were reviewed to determine the primary pathological process resulting in death or the decision to euthanize. Cases were categorized as non-infectious (34/59; 58%), infectious/inflammatory (17/59; 29%) or undetermined due to advanced autolysis (8/59; 14%). Musculoskeletal diseases and reproductive losses were the most frequent pathological processes. Among the infectious processes identified, bacterial infections of the reproductive and haemolymphatic systems were most frequently observed. The first two reports of neoplasia in small flying foxes (Pteropus hypomelanus) are described. Bats under managed care present with a wide range of histopathological lesions. In this cohort, non-infectious disease processes were common.}, journal={Journal of Comparative Pathology}, publisher={Elsevier BV}, author={Kirejczyk, Shannon G.M. and Goodwin, Chloe and Gyimesi, Zoltan S. and Zachariah, Trevor T. and Sturgeon, Ginger L. and Armwood, Abigail R. and Frontera-Acevedo, Karelma and Kokosinksa, Anna and Seguel, Mauricio and Fogelson, Susan B. and et al.}, year={2021}, month={May}, pages={96–107} }
 @article{evans_day_chu_garner_sakamoto_moorhead_2021, title={A rapid, parasite-dependent cellular response to Dirofilaria immitis in the Mongolian jird (Meriones unguiculatus)}, volume={14}, DOI={10.1186/s13071-020-04455-x}, abstractNote={Abstract Background The Mongolian jird ( Meriones unguiculatus ) has long been recognized as a permissive host for the filarial parasite Brugia malayi ; however, it is nonpermissive to another filarial parasite, canine heartworm ( Dirofilaria immitis ). By elucidating differences in the early response to infection, we sought to identify mechanisms involved in the species-specific clearance of these parasites. We hypothesized that the early clearance of D. immitis in intraperitoneal infection of the jird is immune mediated and parasite species dependent. Methods Jird peritoneal exudate cells (PECs) were isolated and their attachment to parasite larvae assessed in vitro under various conditions: D. immitis and B. malayi cultured separately, co-culture of both parasites, incubation before addition of cells, culture of heat-killed parasites, and culture with PECs isolated from jirds with mature B. malayi infection. The cells attaching to larvae were identified by immunohistochemistry. Results In vitro cell attachment to live D. immitis was high (mean = 99.6%) while much lower for B. malayi (mean = 5.56%). This species-specific attachment was also observed when both filarial species were co-cultured, with no significant change from controls ( U (9, 14) = 58.5, p = 0.999). When we replicated these experiments with PECs derived from jirds subcutaneously infected with B. malayi , the results were similar (99.4% and 4.72% of D. immitis and B. malayi , respectively, exhibited cell attachment). Heat-killing the parasites significantly reduced cell attachment to D. immitis (mean = 71.9%; U (11, 14) = 7.5, p < 0.001) while increasing attachment to B. malayi (mean = 16.7%; U (9, 15) = 20, p = 0.002). Cell attachment to both species was reduced when larvae were allowed a 24-h pre-incubation period prior to the addition of cells. The attaching cells were identified as macrophages by immunohistochemistry. Conclusions These results suggest a strongly species-dependent response from which B. malayi could not confer protection by proxy in co-culture. The changes in cell attachment following heat-killing and pre-incubation suggest a role for excretory/secretory products in host immune evasion and/or antigenicity. The nature of this attachment is the subject of ongoing study and may provide insight into filarial host specificity. Graphical Abstract}, number={1}, journal={Parasites and Vectors}, publisher={Springer Science and Business Media LLC}, author={Evans, CC and Day, KM and Chu, Y and Garner, B and Sakamoto, K and Moorhead, AR}, year={2021}, month={Dec} }
 @article{li_honda-okubo_huang_jang_carlock_baldwin_piplani_bebin-blackwell_forgacs_sakamoto_et al._2021, title={Immunisation of ferrets and mice with recombinant SARS-CoV-2 spike protein formulated with Advax-SM adjuvant protects against COVID-19 infection}, volume={39}, DOI={10.1016/j.vaccine.2021.07.087}, abstractNote={The development of a safe and effective vaccine is a key requirement to overcoming the COVID-19 pandemic. Recombinant proteins represent the most reliable and safe vaccine approach but generally require a suitable adjuvant for robust and durable immunity. We used the SARS-CoV-2 genomic sequence and in silico structural modelling to design a recombinant spike protein vaccine (Covax-19™). A synthetic gene encoding the spike extracellular domain (ECD) was inserted into a baculovirus backbone to express the protein in insect cell cultures. The spike ECD was formulated with Advax-SM adjuvant and first tested for immunogenicity in C57BL/6 and BALB/c mice. Covax-19 vaccine induced high spike protein binding antibody levels that neutralised the original lineage B.1.319 virus from which the vaccine spike protein was derived, as well as the variant B.1.1.7 lineage virus. Covax-19 vaccine also induced a high frequency of spike-specific CD4 + and CD8 + memory T-cells with a dominant Th1 phenotype associated with the ability to kill spike-labelled target cells in vivo. Ferrets immunised with Covax-19 vaccine intramuscularly twice 2 weeks apart made spike receptor binding domain (RBD) IgG and were protected against an intranasal challenge with SARS-CoV-2 virus given two weeks after the last immunisation. Notably, ferrets that received the two higher doses of Covax-19 vaccine had no detectable virus in their lungs or in nasal washes at day 3 post-challenge, suggesting that in addition to lung protection, Covax-19 vaccine may have the potential to reduce virus transmission. This data supports advancement of Covax-19 vaccine into human clinical trials.}, number={40}, journal={Vaccine}, publisher={Elsevier BV}, author={Li, L and Honda-Okubo, Y and Huang, Y and Jang, H and Carlock, MA and Baldwin, J and Piplani, S and Bebin-Blackwell, AG and Forgacs, D and Sakamoto, K and et al.}, year={2021}, month={Sep}, pages={5940–5953} }
 @inproceedings{reyes_goodwin_schneider_howerth_sakamoto_donovan_miller_rissi_2021, title={Leptomeningeal Gliomatosis in Dogs and Cats}, author={Reyes, V and Goodwin, C and Schneider, S and Howerth, E and Sakamoto, K and Donovan, T and Miller, A and Rissi, D}, year={2021}, month={Oct} }
 @article{ezenwa_budischak_buss_seguel_luikart_jolles_sakamoto_2021, title={Natural resistance to worms exacerbates bovine tuberculosis severity independently of worm coinfection}, volume={118}, DOI={10.1073/pnas.2015080118}, abstractNote={Pathogen interactions arising during coinfection can exacerbate disease severity, for example when the immune response mounted against one pathogen negatively affects defense of another. It is also possible that host immune responses to a pathogen, shaped by historical evolutionary interactions between host and pathogen, may modify host immune defenses in ways that have repercussions for other pathogens. In this case, negative interactions between two pathogens could emerge even in the absence of concurrent infection. Parasitic worms and tuberculosis (TB) are involved in one of the most geographically extensive of pathogen interactions, and during coinfection worms can exacerbate TB disease outcomes. Here, we show that in a wild mammal natural resistance to worms affects bovine tuberculosis (BTB) severity independently of active worm infection. We found that worm-resistant individuals were more likely to die of BTB than were nonresistant individuals, and their disease progressed more quickly. Anthelmintic treatment moderated, but did not eliminate, the resistance effect, and the effects of resistance and treatment were opposite and additive, with untreated, resistant individuals experiencing the highest mortality. Furthermore, resistance and anthelmintic treatment had nonoverlapping effects on BTB pathology. The effects of resistance manifested in the lungs (the primary site of BTB infection), while the effects of treatment manifested almost entirely in the lymph nodes (the site of disseminated disease), suggesting that resistance and active worm infection affect BTB progression via distinct mechanisms. Our findings reveal that interactions between pathogens can occur as a consequence of processes arising on very different timescales.}, number={3}, journal={Proceedings of the National Academy of Sciences of the United States of America}, publisher={Proceedings of the National Academy of Sciences}, author={Ezenwa, VO and Budischak, SA and Buss, P and Seguel, M and Luikart, G and Jolles, AE and Sakamoto, K}, year={2021}, month={Jan} }
 @article{pfeifle_beasley_crabtree_fraser_elbert_ducker_nagata_garner_sakamoto_2021, title={Osteosarcoma in the femur of a horse}, volume={33}, DOI={10.1111/eve.13445}, abstractNote={Summary A 27‐year‐old Arabian pony gelding presented for evaluation of weight loss, intermittent sheath oedema, persistent neutropenia and thrombocytopenia, and acute left hindlimb swelling and gait abnormality. Clinical findings included swelling, heat and sensitivity localised over the left greater trochanter, mild to moderate ventral and sheath oedema, a left hindlimb post‐legged gait, and off‐loading of weight from the left hindlimb at rest. Initially, neutropenia and thrombocytopenia were confirmed on bloodwork, but neutrophilia and thrombocytopenia persisted as the case progressed. Diagnostic imaging (radiography and percutaneous ultrasonography) of the left hindquarters revealed an aggressive, mixed proliferative and lytic bony lesion of the proximal left femur as well as associated muscle fibre disruption and a soft tissue mass. A percutaneous core biopsy of the lesion led to the diagnosis of osteoblastic osteosarcoma on histopathology. Pain and inflammation associated with the lesion was medically managed in the hospital with mild improvement. Additionally, palliative radiation was performed under general anaesthesia. Unfortunately, before a response to palliative radiation could be assessed, the patient was subjected to euthanasia due to development of acute neurological signs.}, number={11}, journal={Equine Veterinary Education}, publisher={Wiley}, author={Pfeifle, RL and Beasley, EM and Crabtree, NE and Fraser, C and Elbert, JA and Ducker, E and Nagata, K and Garner, BC and Sakamoto, K}, year={2021}, month={Nov} }
 @article{kelly_kasperbauer_sakamoto_camus_mayer_divers_cazzini_2021, title={Pathology in Practice}, volume={259}, DOI={10.2460/javma.259.3.257}, number={3}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Kelly, DL and Kasperbauer, KA and Sakamoto, K and Camus, MS and Mayer, J and Divers, SJ and Cazzini, P}, year={2021}, month={Aug}, pages={257–260} }
 @article{an_li_rowe_diaz_griffin_beavis_johnson_padykula_jones_briggs_et al._2021, title={Protection of K18-hACE2 mice and ferrets against SARS-CoV-2 challenge by a single-dose mucosal immunization with a parainfluenza virus 5–based COVID-19 vaccine}, volume={7}, DOI={10.1126/sciadv.abi5246}, abstractNote={Single-dose intranasal COVID-19 vaccine prevents infection and inhibits transmission.}, number={27}, journal={Science Advances}, publisher={American Association for the Advancement of Science (AAAS)}, author={An, D and Li, K and Rowe, DK and Diaz, MCH and Griffin, EF and Beavis, AC and Johnson, SK and Padykula, I and Jones, CA and Briggs, K and et al.}, year={2021}, month={Jul} }
 @article{wyatt_sakamoto_watford_2022, title={Tamoxifen administration induces histopathologic changes within the lungs of Cre-recombinase-negative mice: A case report}, volume={56}, DOI={10.1177/00236772211042968}, abstractNote={Tamoxifen is commonly used as a cancer treatment in humans and for inducing genetic alterations using Cre-lox mouse models in the research setting. However, the extent of tamoxifen off-target effects in animal research is underappreciated. Here, we report significant changes in cellular infiltration in Cre-recombinase-negative mice treated with tamoxifen intraperitoneally. These changes were noted in the lungs, which were characterized by the presence of alveolitis, vasculitis, and pleuritis. Despite significant immunological changes in response to tamoxifen treatment, clinical symptoms were not observed. This study provides a cautionary note that tamoxifen treatment alone leads to histologic alterations that may obscure research interpretations and further highlights the need for the development of alternative mouse models for inducible Cre-mediated deletion.}, number={3}, journal={Laboratory Animals}, publisher={SAGE Publications}, author={Wyatt, KD and Sakamoto, K and Watford, WT}, year={2022}, month={Jun}, pages={297–303} }
 @article{lopez_2020, title={Characterizing Emerging Canine H3 Influenza Viruses}, volume={16}, DOI={10.1371/journal.ppat.1008409}, abstractNote={The continual emergence of novel influenza A strains from non-human hosts requires constant vigilance and the need for ongoing research to identify strains that may pose a human public health risk. Since 1999, canine H3 influenza A viruses (CIVs) have caused many thousands or millions of respiratory infections in dogs in the United States. While no human infections with CIVs have been reported to date, these viruses could pose a zoonotic risk. In these studies, the National Institutes of Allergy and Infectious Diseases (NIAID) Centers of Excellence for Influenza Research and Surveillance (CEIRS) network collaboratively demonstrated that CIVs replicated in some primary human cells and transmitted effectively in mammalian models. While people born after 1970 had little or no pre-existing humoral immunity against CIVs, the viruses were sensitive to existing antivirals and we identified a panel of H3 cross-reactive human monoclonal antibodies (hmAbs) that could have prophylactic and/or therapeutic value. Our data predict these CIVs posed a low risk to humans. Importantly, we showed that the CEIRS network could work together to provide basic research information important for characterizing emerging influenza viruses, although there were valuable lessons learned.}, number={4}, journal={PLoS Pathogens}, publisher={Public Library of Science (PLoS)}, year={2020}, month={Apr}, pages={e1008409–e1008409} }
 @article{clinical assessment of heartworm‐infected beagles treated with a combination of imidacloprid/moxidectin and doxycycline, or untreated_2020, volume={34}, DOI={10.1111/jvim.15853}, abstractNote={Abstract Background Administration of moxidectin topically and doxycycline PO has been utilized experimentally as an alternative treatment for heartworm disease. However, clinical effects of this protocol remain poorly characterized. Objective To evaluate the clinical and postmortem findings associated with administration of doxycycline and monthly 10% imidacloprid + 2.5% moxidectin (IMD + MOX, Advantage Multi/Advocate) to Dirofilaria immitis ‐experimentally infected as compared to nontreated control dogs. Animals Sixteen purpose‐bred, female, Beagle dogs. Methods Prospective, blinded, experimental study. Animals with surgically transplanted adult heartworms were randomized into 2 study groups of equal size: a nontreated control group (n = 8) and an IMD + MOX and doxycycline‐treated group (n = 8). Randomization was performed using a complete block design according to circulating microfilarial concentrations, measured before treatment. Serum biochemical profiles, CBCs, thoracic radiographs and echocardiograms were performed prior to and 3 weeks after transplantation, and monthly for 10 months. Postmortem gross and histopathologic evaluations were performed. Results Compared to control animals, mean ± SD serum alanine aminotransferase (181 ± 203 U/L vs 33 ± 7 U/L; P < .0001) and alkaline phosphatase (246 ± 258 U/L vs 58 ± 19 U/L; P < .0001) activities were significantly higher in the treated group on day 28. Radiographic and echocardiographic evidence of heartworm disease was observed in both groups; however, no significant differences in these variables were noted between groups. Mean ± SD pulmonary arterial thrombus score was significantly higher in the treated vs nontreated group (3.9 ± 0.4 and 1.5 ± 2.1, respectively; P = .01). Conclusions and Clinical Importance The treatment protocol was well‐tolerated with no clinically relevant adverse effects for any variable evaluated during the observational period.}, number={5}, journal={Journal of Veterinary Internal Medicine (JVIM)}, publisher={Wiley}, year={2020}, month={Sep}, pages={1734–1745} }
 @article{siepker_dalton_mchale_sakamoto_rissi_2020, title={Neuropathology and diagnostic features of rabies in a litter of piglets, with a brief review of the literature}, volume={32}, url={https://doi.org/10.1177/1040638719898687}, DOI={10.1177/1040638719898687}, abstractNote={Porcine rabies is exceedingly rare worldwide. We describe herein the neuropathology and the diagnostic features of an outbreak of rabies in a litter of piglets attacked by a skunk in Georgia, United States. Rabies viral infection was confirmed in 2 of 3 piglets submitted for testing. Inflammatory and degenerative changes were more prominent in the brainstem and consisted of lymphoplasmacytic meningoencephalitis with glial nodules, neuronal necrosis, and neuronophagia. No viral inclusions (Negri bodies) were observed in multiple sections of brain. A fluorescent antibody test on fresh samples of brainstem and cerebellum was confirmatory for the eastern United States raccoon rabies virus variant. Immunoreactivity for rabies virus was detected across all brain sections in both cases but was more prominent in the thalamic and brainstem nuclei, as well as in the medial lemniscus. Rabies is an important differential diagnosis in pigs with neurologic disease.}, number={1}, journal={Journal of Veterinary Diagnostic Investigation}, publisher={SAGE Publications}, author={Siepker, Christopher L. and Dalton, Martha F. and McHale, Brittany J. and Sakamoto, Kaori and Rissi, Daniel R.}, year={2020}, month={Jan}, pages={166–168} }
 @misc{filipov_sakamoto_gupta_mote_hogan_readon_2019, title={Manganese-Mycobacterium tuberculosis interactions: central and peripheral effects}, author={Filipov, N and Sakamoto, K and Gupta, T and Mote, R and Hogan, R and Readon, D}, year={2019}, month={Jul} }
 @article{huertas-díaz_phan_elson_nuñez_wei_sakamoto_he_2019, title={Parainfluenza virus 5 (PIV5) amplifying virus-like particles expressing respiratory syncytial virus (RSV) antigens protect mice against RSV infection}, volume={37}, DOI={10.1016/j.vaccine.2019.04.042}, abstractNote={Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and pneumonia in children under one year of age. In addition to causing severe respiratory diseases in children, it is also a major cause of morbidity and mortality among the elderly and immunocompromised individuals. RSV is the most common cause of lower respiratory tract infections, yet there are currently no licensed vaccines. A parainfluenza virus 5 (PIV5)-based amplifying virus-like particle (AVLP), which enables the use of PIV5 RNA transcription/replication machinery to express gene of interest, has recently been developed. We evaluated the PIV5-based AVLP system as a vaccine platform for RSV by incorporating the fusion protein (F) gene and the transcription factor protein (M2-1) gene of RSV into the PIV5-AVLP backbone (AVLP-F and AVLP-M2-1, respectively). Mice immunized with a single dose of the AVLP-F or AVLP-M2-1 developed RSV-F or RSV-M2-1-specific immune responses, respectively. Both vaccine candidates elicited antigen-specific cell-mediated responses at levels comparable to or higher than an RSV infection. Most importantly, each vaccine was able to induce protection against RSV A2 challenge in the mouse model. These results indicate the potential of the PIV5-based AVLP system as a platform for vaccines against RSV infection.}, number={22}, journal={Vaccine}, publisher={Elsevier BV}, author={Huertas-Díaz, MC and Phan, S and Elson, A and Nuñez, I and Wei, H and Sakamoto, K and He, B}, year={2019}, month={May}, pages={2925–2934} }
 @article{cazzini_watson_gottdenker_mayer_reavill_fox_parry_sakamoto_2020, title={Proposed grading scheme for inflammatory bowel disease in ferrets and correlation with clinical signs}, volume={32}, url={https://doi.org/10.1177/1040638719896555}, DOI={10.1177/1040638719896555}, abstractNote={Inflammatory bowel disease (IBD) is an idiopathic, chronic, inflammatory disease of the gastrointestinal tract of companion animals, including ferrets ( Mustela putorius furo). Clinical signs of IBD are nonspecific, and intestinal biopsies are necessary for a definitive diagnosis. A grading scheme has not been established for ferrets. Additionally, the association between histologic severity and clinical signs in ferrets is unknown. We evaluated enteric samples from ferrets diagnosed with IBD, compared histologic grading schemes, and correlated the results with the severity of clinical signs. Enteric sections from 23 ferrets with IBD were analyzed using grading schemes for intestinal inflammation in cats and dogs, and a correlation with clinical signs was evaluated. After dividing the histologic samples into groups based on the severity of clinical signs, main histologic differences were identified. Age and sex were also assessed for correlation with clinical signs. No significant correlation was found between the 2 grading schemes and clinical signs (rho = 0.02, p = 0.89; rho = 0.26, p = 0.18, respectively). Degree of villus fusion, hemorrhage and/or fibrin, epithelial damage, inflammation density, and crypt abscess formation were used retrospectively to create a ferret IBD grading scheme, which was significantly correlated with the severity of clinical signs (rho = 0.48, p = 0.01). A positive correlation was observed between age ( p = 0.04) and females ( p = 0.007) with severity of clinical signs. Our ferret grading scheme may have clinical utility in providing a more objective, consistent evaluation of IBD in ferrets.}, number={1}, journal={Journal of Veterinary Diagnostic Investigation}, publisher={SAGE Publications}, author={Cazzini, Paola and Watson, Megan K. and Gottdenker, Nicole and Mayer, Joerg and Reavill, Drury and Fox, James G. and Parry, Nicola and Sakamoto, Kaori}, year={2020}, month={Jan}, pages={17–24} }
 @article{rosselli_schmiedt_kirejczyk_sakamoto_sinkin_rapoport_2019, title={Surgical resection of a left auricular aneurysm in a dog}, volume={23}, DOI={10.1016/j.jvc.2018.12.004}, abstractNote={Aneurysmal dilation of the atrial appendage (auricle) is rare in humans and dogs. Congenital and acquired etiologies are hypothesized. Although right auricular aneurysm has been described in dogs, this is the first case report of an aneurysm of the left auricle of a dog with an intact pericardium. In humans, because complications of arrhythmia and thromboembolic disease have been reported, surgical resection of left auricular aneurysm is recommended. This report describes the successful surgical resection of a left auricular aneurysm in a dog, including a one-year follow up. Surgical resection can be considered in dogs with auricular aneurysm.}, journal={Journal of Veterinary Cardiology}, publisher={Elsevier BV}, author={Rosselli, D and Schmiedt, C and Kirejczyk, S and Sakamoto, K and Sinkin, A and Rapoport, G}, year={2019}, month={Jun}, pages={15–20} }
 @article{cardiac mesothelial papillary hyperplasia in four dogs_2018, volume={30}, DOI={10.1177/1040638717753964}, abstractNote={Mesothelial papillary hyperplasia (MPH) has been described as an incidental finding on the epicardial surface of clinically normal laboratory Beagle dogs. We describe MPH in 4 dogs diagnosed with acute cardiac tamponade (1 case) or chronic cardiac disease (3 cases). Cardiac MPH appeared as distinct, soft, irregular villous plaques on the epicardial surface of the auricles and occasionally the ventricles. Histologically, areas of MPH were composed of multiple papillary fronds arising from the epicardial surface and projecting into the pericardial space. Fronds were covered by cuboidal and occasionally vacuolated mesothelial cells and were supported by loose fibrovascular stroma with various degrees of edema and inflammation. Although these may represent incidental findings with no clinical significance, the gross appearance warrants differentiation from other conditions. Additional insight into the pathogenesis of MPH is needed to fully understand its significance in the face of concurrent cardiac disease.}, number={3}, journal={Journal of Veterinary Diagnostic Investigation}, publisher={SAGE Publications}, year={2018}, month={May}, pages={479–482} }
 @article{wong_chambers_elsmo_jenkins_howerth_sánchez_sakamoto_2018, title={Cellulitis caused by the <i>Burkholderia cepacia</i> complex associated with contaminated chlorhexidine 2% scrub in five domestic cats}, volume={30}, DOI={10.1177/1040638718782333}, abstractNote={Isolates of the Burkholderia cepacia complex (BCC) are known as plant and human pathogens. We describe herein BCC infections as the cause of subcutaneous abscesses and purulent cellulitis in 5 cats. All cats were presented with an open wound, and 4 received standard wound care and empiric antibiotic therapy. Despite treatment, clinical signs worsened in 4 cats. Isolates of the BCC were obtained from all 5 cases. Two cats were submitted for postmortem examination. Subcutaneous abscesses with draining fistulas were observed. Histopathology revealed severe, pyogranulomatous cellulitis with intralesional gram-negative bacilli. Based on susceptibility results, the other 3 cats were administered effective antibiotics and recovered without complications. The BCC was cultured from the 2% chlorhexidine surgical scrub solution used in the clinic, suggesting the source of infection for 4 of 5 cats. Given the ability to grow in antiseptic solutions, the extra steps required to culture from antiseptics, and innate multidrug resistance, the BCC poses a challenge to both detect and treat. Although the BCC causes disease almost exclusively in humans with cystic fibrosis or immunodeficiency, the bacteria should also be a differential for nosocomial infections in veterinary patients.}, number={5}, journal={Journal of Veterinary Diagnostic Investigation}, publisher={SAGE Publications}, author={Wong, JK and Chambers, LC and Elsmo, EJ and Jenkins, TL and Howerth, EW and Sánchez, S and Sakamoto, K}, year={2018}, month={Sep}, pages={763–769} }
 @article{gupta_lagatta_helms_pavlicek_owino_sakamoto_nagy_harvey_papania_ledden_et al._2018, title={Evaluation of a temperature-restricted, mucosal tuberculosis vaccine in guinea pigs}, volume={113}, DOI={10.1016/j.tube.2018.10.006}, abstractNote={Tuberculosis (TB) is currently the leading cause of death in humans by a single infectious agent, Mycobacterium tuberculosis. The Bacillus Calmette-Guérin (BCG) vaccine prevents pulmonary TB with variable efficacy, but can cause life-threatening systemic infection in HIV-infected infants. In this study, TBvac85, a derivative of Mycobacterium shottsii expressing M. tuberculosis Antigen 85B, was examined as a safer alternative to BCG. Intranasal vaccination of guinea pigs with TBvac85, a naturally temperature-restricted species, resulted in serum Ag85B-specific IgG antibodies. Delivery of the vaccine by this route also induced protection equivalent to intradermal BCG based on organ bacterial burdens and lung pathology six weeks after aerosol challenge with M. tuberculosis strain Erdman. These results support the potential of TBvac85 as the basis of an effective TB vaccine. Next-generation derivatives expressing multiple M. tuberculosis immunogens are in development.}, journal={Tuberculosis}, publisher={Elsevier BV}, author={Gupta, T and LaGatta, M and Helms, S and Pavlicek, RL and Owino, SO and Sakamoto, K and Nagy, T and Harvey, SB and Papania, M and Ledden, S and et al.}, year={2018}, month={Dec}, pages={179–188} }
 @inproceedings{gupta_helms_sakamoto_harvey_ross_whalen_karls_quinn_2018, title={Ferret transmission model for tuberculosis}, author={Gupta, T and Helms, S and Sakamoto, K and Harvey, S and Ross, T and Whalen, C and Karls, R and Quinn, F}, year={2018}, month={Jun} }
 @article{abraham_arroyo-diaz_li_zengel_sakamoto_he_2018, title={Role of Small Hydrophobic Protein of J Paramyxovirus in Virulence}, volume={92}, DOI={10.1128/jvi.00653-18}, abstractNote={Paramyxoviruses are associated with many devastating diseases in animals and humans. J paramyxovirus (JPV) was isolated from moribund mice in Australia in 1972. Newly isolated viruses, such as Beilong virus (BeiPV) and Tailam virus (TlmPV), have genome structures similar to that of JPV. A new paramyxovirus genus, Jeilongvirus , which contains JPV, BeiPV, and TlmPV, has been proposed. Small hydrophobic (SH) protein is present in many paramyxoviruses. Our present study investigates the role of SH protein of JPV in pathogenesis in its natural host. Understanding the pathogenic mechanism of Jeilongvirus is important to control and prevent potential diseases that may emerge from this group of viruses.}, number={20}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Abraham, M and Arroyo-Diaz, NM and Li, Z and Zengel, J and Sakamoto, K and He, B}, editor={Dutch, REEditor}, year={2018}, month={Oct} }
 @article{koenig_cooper_greene_sharma_sakamoto_2017, title={Clinical Salmonellosis in a Closed Colony of Blood Donor Cats}, volume={67}, number={6}, journal={Comparative Medicine}, publisher={AMER ASSOC LABORATORY ANIMAL SCIENCE}, author={Koenig, A and Cooper, TL and Greene, CE and Sharma, A and Sakamoto, K}, year={2017}, month={Dec}, pages={524–528} }
 @article{wei_chen_elson_li_abraham_phan_kristhnamurthy_mccray_andrews_stice_et al._2017, title={Developing a platform system for gene delivery: amplifying virus-like particles (AVLP) as an influenza vaccine}, volume={2}, DOI={10.1038/s41541-017-0031-7}, abstractNote={Delivery of a gene of interest to target cells is highly desirable for translational medicine, such as gene therapy, regenerative medicine, vaccine development, and studies of gene function. Parainfluenza virus 5 (PIV5), a paramyxovirus with a negative-sense RNA genome, normally infects cells without causing obvious cytopathic effect, and it can infect many cell types. To exploit these features of PIV5, we established a system generating self-amplifying, virus-like particles (AVLP). Using enhanced green fluorescent protein (EGFP) as a reporter, AVLP encoding EGFP (AVLP-EGFP) successfully delivered and expressed the EGFP gene in primary human cells, including stem cells, airway epithelial cells, monocytes, and T cells. To demonstrate the application of this system for vaccine development, we generated AVLPs to express the HA and M1 antigens from the influenza A virus strain H5N1 (AVLP-H5 and AVLP-M1H5). Immunization of mice with AVLP-H5 and AVLP-M1H5 generated robust antibody and cellular immune responses. Vaccination with a single dose of AVLP-H5 and M1H5 completely protected mice against lethal H5N1 challenge, suggesting that the AVLP-based system is a promising platform for delivery of desirable genes.}, number={1}, journal={npj Vaccines}, publisher={Springer Science and Business Media LLC}, author={Wei, H and Chen, Z and Elson, A and Li, Z and Abraham, M and Phan, S and Kristhnamurthy, S and McCray, PB and Andrews, S and Stice, S and et al.}, year={2017}, month={Nov} }
 @inproceedings{ciappa_gupta_lewis_sakamoto_karls_2017, title={Examination of Mycobacterium tuberculosis protein expression in infected lung tissue}, author={Ciappa, N and Gupta, T and Lewis, MB and Sakamoto, K and Karls, R}, year={2017}, month={Apr} }
 @misc{ciappa_gupta_hikal_lewis_sakamoto_karls_2017, title={Examining the potential of Mycobacterium tuberculosis CtpB in copper transport}, author={Ciappa, N and Gupta, T and Hikal, A and Lewis, MB and Sakamoto, K and Karls, R}, year={2017}, month={Apr} }
 @misc{gupta_helms_sakamoto_harvey_ross_whalen_karls_quinn_2017, title={Ferret transmission model for tuberculosis}, author={Gupta, T and Helms, S and Sakamoto, K and Harvey, S and Ross, T and Whalen, C and Karls, R and Quinn, F}, year={2017}, month={Jun} }
 @inproceedings{gupta_quinn_lagatta_helms_jacobs_owino_jarrett_sakamoto_harvey_whalen_et al._2017, title={Ferrets as a transmission model for tuberculosis}, author={Gupta, T and Quinn, F and Lagatta, M and Helms, S and Jacobs, W and Owino, S and Jarrett, S and Sakamoto, K and Harvey, S and Whalen, C and et al.}, year={2017}, month={Jan} }
 @misc{gupta_day_rowe_lagatta_helms_helms_jacobs_owino_sweenly_sakamoto_et al._2017, title={Ferrets as a transmission model for tuberculosis}, publisher={University of Georgia}, author={Gupta, T and Day, C and Rowe, T and Lagatta, M and Helms, S and Helms, S and Jacobs, W and Owino, S and Sweenly, J and Sakamoto, K and et al.}, year={2017}, month={Feb} }
 @book{moorhead_jones_sakamoto_2017, place={Duluth, Georgia}, title={Heartworm}, publisher={Merial}, author={Moorhead, A.R. and Jones, S. and Sakamoto, K.}, year={2017} }
 @article{novakowski_yap_yin_sakamoto_heit_golding_bowdish_2018, title={Human-Specific Mutations and Positively Selected Sites in MARCO Confer Functional Changes}, volume={35}, DOI={10.1093/molbev/msx298}, abstractNote={Macrophage Receptor with COllagenous structure (MARCO) is a class A scavenger receptor that binds, phagocytoses, and modifies inflammatory responses to bacterial pathogens. Multiple candidate gene approach studies have shown that polymorphisms in MARCO are associated with susceptibility or resistance to Mycobacterium tuberculosis infection, but how these variants alter function is not known. To complement candidate gene approach studies, we previously used phylogenetic analyses to identify a residue, glutamine 452 (Q452), within the ligand-binding Scavenger Receptor Cysteine Rich domain as undergoing positive selection in humans. Herein, we show that Q452 is found in Denisovans, Neanderthals, and extant humans, but all other nonprimate, terrestrial, and aquatic mammals possess an aspartic acid (D452) residue. Further analysis of hominoid sequences of MARCO identified an additional human-specific mutation, phenylalanine 282 (F282), within the collagenous domain. We show that residue 282 is polymorphic in humans, but only 17% of individuals (rs6761637) possess the ancestral serine residue at position 282. We show that rs6761637 is in linkage disequilibrium with MARCO polymorphisms that have been previously linked to susceptibility to pulmonary tuberculosis. To assess the functional importance of sites Q452 and F282 in humans, we cloned the ancestral residues and loss-of-function mutations and investigated the role of these residues in binding and internalizing polystyrene microspheres and Escherichia coli. Herein, we show that the residues at sites 452 and 282 enhance receptor function.}, number={2}, journal={Molecular Biology and Evolution (MBE)}, publisher={Oxford University Press (OUP)}, author={Novakowski, KE and Yap, NVL and Yin, C and Sakamoto, K and Heit, B and Golding, GB and Bowdish, DME}, year={2018}, month={Feb}, pages={440–450} }
 @book{moorhead_sakamoto_2017, title={Toxocara canis}, author={Moorhead, A.R. and Sakamoto, K.}, year={2017} }
 @article{stobart_rostad_ke_dillard_hampton_strauss_yi_hotard_meng_pickles_et al._2016, title={A live RSV vaccine with engineered thermostability is immunogenic in cotton rats despite high attenuation}, volume={7}, DOI={10.1038/ncomms13916}, abstractNote={Abstract Respiratory syncytial virus (RSV) is a leading cause of infant hospitalization and there remains no pediatric vaccine. RSV live-attenuated vaccines (LAVs) have a history of safe testing in infants; however, achieving an effective balance of attenuation and immunogenicity has proven challenging. Here we seek to engineer an RSV LAV with enhanced immunogenicity. Genetic mapping identifies strain line 19 fusion (F) protein residues that correlate with pre-fusion antigen maintenance by ELISA and thermal stability of infectivity in live RSV. We generate a LAV candidate named OE4 which expresses line 19F and is attenuated by codon-deoptimization of non-structural (NS1 and NS2) genes, deletion of the small hydrophobic (SH) gene, codon-deoptimization of the attachment (G) gene and ablation of the secreted form of G. OE4 (RSV-A2-dNS1-dNS2-ΔSH-dG m -Gs null -line19F) exhibits elevated pre-fusion antigen levels, thermal stability, immunogenicity, and efficacy despite heavy attenuation in the upper and lower airways of cotton rats.}, number={1}, journal={Nature Communications}, publisher={Springer Science and Business Media LLC}, author={Stobart, CC and Rostad, CA and Ke, Z and Dillard, RS and Hampton, CM and Strauss, JD and Yi, H and Hotard, AL and Meng, J and Pickles, RJ and et al.}, year={2016}, month={Dec} }
 @article{a naturally occurring transcript variant of marco reveals the srcr domain is critical for function_2016, volume={94}, DOI={10.1038/icb.2016.20}, abstractNote={Macrophage receptor with collagenous structure (MARCO) is a class A scavenger receptor (cA‐SR) that recognizes and phagocytoses a wide variety of pathogens. Most cA‐SRs that contain a C‐terminal scavenger receptor cysteine‐rich (SRCR) domain use the proximal collagenous domain to bind ligands. In contrast, the role of the SRCR domain of MARCO in phagocytosis, adhesion and pro‐inflammatory signaling is less clear. The discovery of a naturally occurring transcript variant lacking the SRCR domain, MARCOII, provided the opportunity to study the role of the SRCR domain of MARCO. We tested whether the SRCR domain is required for ligand binding, promoting downstream signaling and enhancing cellular adhesion. Unlike cells expressing full‐length MARCO, ligand binding was abolished in MARCOII‐expressing cells. Furthermore, co‐expression of MARCO and MARCOII impaired phagocytic function, indicating that MARCOII acts as a dominant‐negative variant. Unlike MARCO, expression of MARCOII did not enhance Toll‐like receptor 2 (TLR2)‐mediated pro‐inflammatory signaling in response to bacterial stimulation. MARCO‐expressing cells were more adherent and exhibited a dendritic‐like phenotype, whereas MARCOII‐expressing cells were less adherent and did not exhibit changes in morphology. These data suggest the SRCR domain of MARCO is the key domain in modulating ligand binding, enhancing downstream pro‐inflammatory signaling and MARCO‐mediated cellular adhesion.}, number={7}, journal={Immunology and Cell Biology}, publisher={Wiley}, year={2016}, month={Aug}, pages={646–655} }
 @article{heise_2016, title={EGFR Interacts with the Fusion Protein of Respiratory Syncytial Virus Strain 2-20 and Mediates Infection and Mucin Expression}, volume={12}, DOI={10.1371/journal.ppat.1005622}, abstractNote={Respiratory syncytial virus (RSV) is the major cause of viral lower respiratory tract illness in children. In contrast to the RSV prototypic strain A2, clinical isolate RSV 2-20 induces airway mucin expression in mice, a clinically relevant phenotype dependent on the fusion (F) protein of the RSV strain. Epidermal growth factor receptor (EGFR) plays a role in airway mucin expression in other systems; therefore, we hypothesized that the RSV 2-20 F protein stimulates EGFR signaling. Infection of cells with chimeric strains RSV A2-2-20F and A2-2-20GF or over-expression of 2-20 F protein resulted in greater phosphorylation of EGFR than infection with RSV A2 or over-expression of A2 F, respectively. Chemical inhibition of EGFR signaling or knockdown of EGFR resulted in diminished infectivity of RSV A2-2-20F but not RSV A2. Over-expression of EGFR enhanced the fusion activity of 2-20 F protein in trans. EGFR co-immunoprecipitated most efficiently with RSV F proteins derived from "mucogenic" strains. RSV 2-20 F and EGFR co-localized in H292 cells, and A2-2-20GF-induced MUC5AC expression was ablated by EGFR inhibitors in these cells. Treatment of BALB/c mice with the EGFR inhibitor erlotinib significantly reduced the amount of RSV A2-2-20F-induced airway mucin expression. Our results demonstrate that RSV F interacts with EGFR in a strain-specific manner, EGFR is a co-factor for infection, and EGFR plays a role in RSV-induced mucin expression, suggesting EGFR is a potential target for RSV disease.}, number={5}, journal={PLoS Pathogens}, publisher={Public Library of Science (PLoS)}, year={2016}, month={May}, pages={e1005622–e1005622} }
 @article{watson_cazzini_mayer_gottdenker_reavill_parry_fox_sakamoto_2016, title={Histology and immunohistochemistry of severe inflammatory bowel disease versus lymphoma in the ferret (<i>Mustela putorius furo</i>)}, volume={28}, DOI={10.1177/1040638716641156}, abstractNote={Inflammatory bowel disease (IBD) is a common disorder of ferrets ( Mustela putorius furo) that may progress to lymphoma. Although routine histology is used to distinguish between these diseases, misclassifications may occur. Immunohistochemistry (IHC) is commonly used to distinguish between IBD and lymphoma in small animals. The objective of our study was to determine the agreement in the diagnosis reached solely using hematoxylin and eosin (HE)-stained, full-thickness sections versus using a combination of HE and IHC. Enteric sections from 44 ferrets previously diagnosed with IBD or intestinal lymphoma and 3 control ferrets were analyzed by pathologists with expertise in ferrets. A pathologist blinded to the original diagnosis assessed the same HE-stained sections. Analysis was then repeated using HE sections in parallel with sections stained using antibodies against CD3 and CD79a. No significant difference was found between the original HE diagnosis and the HE diagnosis reached by the blinded pathologist ( p = 0.91) or between the blinded pathologist’s HE versus HE with IHC diagnosis ( p = 0.16). In the 2 cases where disagreement was present, IHC was pivotal in reaching a final diagnosis. There was no significant age ( p = 0.29) difference between diagnoses; however, significantly more male ferrets were affected with IBD than females ( p = 0.004). Immunophenotype of the lymphoma was not correlated with predilection for location in the intestinal wall ( p = 0.44). Results suggest that although IHC is not necessary to distinguish IBD from intestinal lymphoma in ferrets, it can be useful a definitive diagnosis in cases of severe IBD.}, number={3}, journal={Journal of Veterinary Diagnostic Investigation}, publisher={SAGE Publications}, author={Watson, MK and Cazzini, P and Mayer, J and Gottdenker, N and Reavill, D and Parry, N and Fox, JG and Sakamoto, K}, year={2016}, month={May}, pages={198–206} }
 @inproceedings{gupta_lagatta_owino_helms_sakamoto_karls_quinn_2016, title={Long-term survival studies of a novel, live-attenuated, tuberculosis vaccine in the guinea pig model}, author={Gupta, T and LaGatta, M and Owino, S and Helms, S and Sakamoto, K and Karls, RK and Quinn, F}, year={2016}, month={Mar} }
 @article{mycobacteria and autophagy: many questions and few answers_2017, DOI={10.21775/cimb.021.063}, abstractNote={Tuberculosis (TB) is an ancient disease caused by Mycobacterium tuberculosis (Mtb).TB is one of the world's deadliest diseases, with one-third of infected individuals falling ill each year especially in many developing countries.Upon invading host cells, such as macrophages, Mtb can replicate in infected cells by arresting phagosome maturation and then potentially escaping into the cytosol.Host cells have a mechanism to control intracellular Mtb by inducing autophagy, which is an elaborate cellular process to target intracellular pathogens for degradation in infected cells.However, some factors of Mtb are involved in defense against killing by autophagy.Thus, this review highlights the recent advances in the interactions between autophagy and Mtb.}, journal={Current Issues in Molecular Biology}, publisher={MDPI AG}, year={2017} }
 @book{sakamoto_rissi_yost_blas-machado_brown_brown_ellis_rech_2016, title={Necropsy Protocol}, author={Sakamoto, K. and Rissi, D. and Yost, K. and Blas-Machado, U. and Brown, C. and Brown, C. and Ellis, A.E. and Rech, R.}, year={2016} }
 @article{edwards_garner_williamson_storey_sakamoto_2016, title={Pathology of <i>Haemonchus contortus</i> in New World camelids in the southeastern United States}, volume={28}, ISSN={1040-6387 1943-4936}, url={http://dx.doi.org/10.1177/1040638716628587}, DOI={10.1177/1040638716628587}, abstractNote={Most small ruminant farms in tropical climates are plagued by Haemonchus contortus, a hematophagous, abomasal parasite. Heavy burdens of this parasite can cause anemia, hypoproteinemia, weight loss, and mortality in susceptible animals. Haemonchus contortus is becoming a major health concern in New World camelids as well, namely llamas (Llama glama) and alpacas (Vicugna pacos), yet little research has been conducted regarding its prevalence or pathology in these species. Herein, we present a retrospective review of llamas and alpacas that were admitted to The University of Georgia Veterinary Teaching Hospital and Athens Diagnostic Laboratory between the years 2002 and 2013. Antemortem fecal egg count (FEC) estimates performed on 30 alpacas were negatively correlated with hematocrit, hemoglobin, and red blood cell count. Total protein was not significantly correlated with FEC. On postmortem examination, 55 of 198 camelids, including 2 from the aforementioned antemortem review, were infected with H. contortus, with llamas (42.6%) having a significantly higher infection rate than alpacas (22.2%). In 15.7% of the total cases, the parasite was the major cause of death. Common gross lesions included peritoneal, thoracic, and pericardial effusions, visceral pallor, subcutaneous edema, and serous atrophy of fat. Histologic lesions included centrilobular hepatic necrosis, hepatic atrophy, lymphoplasmacytic inflammation of the mucosa of the third gastric compartment (C3), extramedullary hematopoiesis in both the liver and spleen, and the presence of nematodes in C3. Our study emphasizes the importance of H. contortus diagnosis and herd monitoring in New World camelids, particularly llamas.}, number={2}, journal={Journal of Veterinary Diagnostic Investigation}, publisher={SAGE Publications}, author={Edwards, Erin E. and Garner, Bridget C. and Williamson, Lisa H. and Storey, Bob E. and Sakamoto, Kaori}, year={2016}, month={Mar}, pages={105–109} }
 @article{palomares_sakamoto_walz_brock_hurley_2015, title={Acute infection with bovine viral diarrhea virus of low or high virulence leads to depletion and redistribution of WC1+ γδ T cells in lymphoid tissues of beef calves}, volume={167}, DOI={10.1016/j.vetimm.2015.07.016}, abstractNote={The objective of this study was to determine the abundance and distribution of γδ T lymphocytes in lymphoid tissue during acute infection with high (HV) or low virulence (LV) non-cytopathic bovine viral diarrhea virus (BVDV) in beef calves. This study was performed using tissue samples from a previous experiment in which thirty beef calves were randomly assigned to 1 of 3 groups: LV [n = 10; animals inoculated intranasally (IN) with LV BVDV-1a (strain SD-1)], HV [n = 10; animals inoculated IN with HV BVDV-2 (strain 1373)], and control (n = 10; animals inoculated with cell culture medium). On day 5 post inoculation, animals were euthanized, and samples from spleen and mesenteric lymph nodes (MLN) were collected to assess the abundance of WC1+ γδ T cells. A higher proportion of calves challenged with BVDV showed signs of apoptosis and cytophagy in MLN and spleen samples compared to the control group. A significantly lower number of γδ T cells was observed in spleen and MLN from calves in HV and LV groups than in the control calves (P < 0.05). In conclusion, acute infection with HV or LV BVDV resulted in depletion of WC1+ γδ T cells in mucosal and systemic lymphoid tissues at five days after challenge in beef calves. This reduction in γδ T cells in the studied lymphoid tissues could be also due to lymphocyte trafficking to other tissues.}, number={3-4}, journal={Veterinary Immunology and Immunopathology}, publisher={Elsevier BV}, author={Palomares, RA and Sakamoto, K and Walz, HL and Brock, KV and Hurley, DJ}, year={2015}, month={Oct}, pages={190–195} }
 @article{comolli_olsen_seguel_schnellbacher_fox_divers_sakamoto_2015, title={Ameloblastoma in a wild black rat snake (<i>Pantherophis alleghaniensis</i>)}, volume={27}, DOI={10.1177/1040638715590652}, abstractNote={Reports of neoplasia in captive reptiles are becoming more frequent; however, there is still scarce knowledge of the occurrence of neoplasia in wild reptiles. A wild black rat snake ( Pantherophis alleghaniensis) was presented to the Zoological Medicine service of the University of Georgia’s Veterinary Teaching Hospital with a 3 cm in diameter solid mandibular mass that was partially ulcerated. Radiographically, the mass was radiopaque with small bone spicules and partial osteolysis of the adjacent mandible. Histologic examination of the mass revealed a neoplasm composed of cuboidal to polygonal cells arranged in islands, anastomosing cords, and trabeculae of pseudostratified epithelium with a palisading peripheral layer of densely packed columnar cells with cytoplasmic clearing. The neoplastic tissue was separated from the mesenchyme by a prominent band of fine collagen. Neoplastic cells were positive for cytokeratin and negative for smooth muscle actin. Electron microscopy highlighted the presence of tonofilaments and microvilli. These findings led to the diagnosis of ameloblastoma, an odontogenic epithelial tumor known to occur in humans and most veterinary species.}, number={4}, journal={Journal of Veterinary Diagnostic Investigation}, publisher={SAGE Publications}, author={Comolli, JR and Olsen, HMH and Seguel, M and Schnellbacher, RW and Fox, AJ and Divers, SJ and Sakamoto, K}, year={2015}, month={Jul}, pages={536–539} }
 @inproceedings{gupta_chen_lagatta_sakamoto_karls_quinn_he_2015, title={Developing a parainfluenza virus 5 (PIV5)-based Mycobacterium tuberculosis vaccine}, author={Gupta, T and Chen, Z and Lagatta, M and Sakamoto, K and Karls, R and Quinn, F and He, B}, year={2015}, month={Apr} }
 @article{chen_gupta_xu_phan_pickar_yau_karls_quinn_sakamoto_he_2015, title={Efficacy of parainfluenza virus 5 (PIV5)-based tuberculosis vaccines in mice}, volume={33}, DOI={10.1016/j.vaccine.2015.10.124}, abstractNote={Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB), is an important human pathogen. Bacillus Calmette-Guérin (BCG), a live, attenuated variant of Mycobacterium bovis, is currently the only available TB vaccine despite its low efficacy against the infectious pulmonary form of the disease in adults. Thus, a more-effective TB vaccine is needed. Parainfluenza virus 5 (PIV5), a paramyxovirus, has several characteristics that make it an attractive vaccine vector. It is safe, inexpensive to produce, and has been previously shown to be efficacious as the backbone of vaccines for influenza, rabies, and respiratory syncytial virus. In this work, recombinant PIV5 expressing M. tuberculosis antigens 85A (PIV5-85A) and 85B (PIV5-85B) have been generated and their immunogenicity and protective efficacy evaluated in a mouse aerosol infection model. In a long-term protection study, a single dose of PIV5-85A was found to be most effective in reducing M. tuberculosis colony forming units (CFU) in lungs when compared to unvaccinated, whereas the BCG vaccinated animals had similar numbers of CFUs to unvaccinated animals. BCG-prime followed by a PIV5-85A or PIV5-85B boost produced better outcomes highlighted by close to three-log units lower lung CFUs compared to PBS. The results indicate that PIV5-based M. tuberculosis vaccines are promising candidates for further development.}, number={51}, journal={Vaccine}, publisher={Elsevier BV}, author={Chen, Z and Gupta, T and Xu, P and Phan, S and Pickar, A and Yau, W and Karls, RK and Quinn, FD and Sakamoto, K and He, B}, year={2015}, month={Dec}, pages={7217–7224} }
 @misc{chen_sakamoto_quinn_chen_fu_2015, title={Fate of Mycobacteria in Murine Brain Microvascular Endothelial Cells}, author={Chen, X and Sakamoto, K and Quinn, F and Chen, H and Fu, Z}, year={2015}, month={Oct} }
 @inproceedings{chen_sakamoto_quinn_chen_fu_2015, title={Fate of Mycobacteria in Murine Brain Microvascular Endothelial Cells}, author={Chen, X and Sakamoto, K and Quinn, F and Chen, H and Fu, Z}, year={2015}, month={Oct} }
 @article{chen_sakamoto_quinn_chen_fu_2015, title={Lack of intracellular replication of <i>M. tuberculosis</i> and <i>M. bovis</i> BCG caused by delivering bacilli to lysosomes in murine brain microvascular endothelial cells}, volume={6}, DOI={10.18632/oncotarget.5932}, abstractNote={Invasion and traversal of the blood-brain barrier (BBB) by Mycobacterium tuberculosis cause meningeal tuberculosis (TB) in the central nervous system (CNS). Meningeal TB is a serious, often fatal disease that disproportionately affects young children. The mechanisms involved in CNS invasion by M. tuberculosis bacilli are poorly understood. In this study, we microscopically examined endosomal trafficking and measured survival of M. tuberculosis and M. bovis Bacille Calmette-Guérin (BCG) bacilli in murine brain microvascular endothelial cells (BMECs). The results show that both species internalize but do not replicate in BMECs in the absence of a cytotoxic response. Confocal microscopy indicates that bacilli-containing vacuoles are associated with the early endosomal marker, Rab5, late endosomal marker, Rab7, and lysosomal marker, LAMP2, suggesting that bacilli-containing endosomes mature into endolysosomes in BMECs. Our data also show that a subset of intracellular M. tuberculosis, but not BCG bacilli, escape into the cytoplasm to avoid rapid lysosomal killing. However, the intracellular mycobacteria examined cannot spread cell-to-cell in BMECs. Taken together, these data show that with the exception of the small terminal cytoplasmic population of bacilli, M. tuberculosis does not modulate intracellular trafficking in BMECs as occurs in macrophages and lung epithelial and endothelial cells.}, number={32}, journal={Oncotarget}, publisher={Impact Journals, LLC}, author={Chen, X and Sakamoto, K and Quinn, FD and Chen, H and Fu, Z}, year={2015}, month={Oct}, pages={32456–32467} }
 @article{cazzini_frontera-acevedo_garner_howerth_torres_northrup_sakamoto_2015, title={Morphologic, molecular, and ultrastructural characterization of a feline synovial cell sarcoma and derived cell line}, volume={27}, DOI={10.1177/1040638715583529}, abstractNote={A 2.5-year-old, male, neutered cat presented with a 5-month history of progressive right hind limb lameness and an enlarged right popliteal lymph node. Radiographs revealed significant bony lysis of the tarsus and distal tibia, and fine-needle aspirate of the bone lesion and lymph node revealed a neoplastic population of cells with uncertain origin. Amputation was elected, and the mass was submitted for histology and cellular culture for better characterization. Histologic examination revealed a mixture of spindle-shaped cells and larger, round to polygonal cells. All cells were immunoreactive for vimentin, and only the larger polygonal cells were also positive for cytokeratin. All cells were negative for desmin, smooth muscle actin, cluster of differentiation (CD)3, CD18, CD79a, macrophage antibody (MAC)387, and glial fibrillary acidic protein. Cultured neoplastic cells failed to express CD18, and were not able to secrete the pro-inflammatory cytokines tumor necrosis factor-α, interleukin-1 (IL-1)β, and IL-6 when stimulated by lipopolysaccharide, disproving that the cells originated from the macrophage or monocyte line. Ultrastructurally, neoplastic cells were characterized by abundant rough endoplasmic reticulum, interdigitating cellular processes, and membrane condensations. Based on location and cytologic, histologic, ultrastructural, and functional studies, this neoplasm was considered a synovial cell sarcoma.}, number={3}, journal={Journal of Veterinary Diagnostic Investigation}, publisher={SAGE Publications}, author={Cazzini, P and Frontera-Acevedo, K and Garner, B and Howerth, E and Torres, B and Northrup, N and Sakamoto, K}, year={2015}, month={May}, pages={369–376} }
 @article{herd_cazzini_houghton_lee_freeman_sakamoto_2015, title={Pathology in Practice}, volume={246}, DOI={10.2460/javma.246.7.749}, number={7}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Herd, HR and Cazzini, P and Houghton, SE and Lee, WL and Freeman, CE and Sakamoto, K}, year={2015}, month={Apr}, pages={749–751} }
 @article{thomason_rapoport_fallaw_calvert_sakamoto_2015, title={Pulmonary edema secondary to a cardiac schwannoma in a dog}, volume={17}, DOI={10.1016/j.jvc.2015.01.006}, abstractNote={A 4-year-old castrated labrador retriever presented for cardiac evaluation to determine the etiology of cardiogenic pulmonary edema diagnosed 1 month prior. A large pedunculated mass involving the ventral aspect of the mural mitral valve leaflet and the endocardial surface of the left ventricular free wall, resulting in severe mitral regurgitation, was identified on echocardiogram. Histopathology and immunohistochemistry of this mass and other endocardial masses identified at necropsy for S-100 protein were consistent with a diagnosis of schwannoma. To the authors' knowledge, this is the first case of a benign intracardiac schwannoma described in the left heart of a dog.}, number={2}, journal={Journal of Veterinary Cardiology}, publisher={Elsevier BV}, author={Thomason, JD and Rapoport, G and Fallaw, T and Calvert, CA and Sakamoto, K}, year={2015}, month={Jun}, pages={149–153} }
 @article{budischak_sakamoto_megow_cummings_urban_ezenwa_2015, title={Resource limitation alters the consequences of co-infection for both hosts and parasites}, volume={45}, DOI={10.1016/j.ijpara.2015.02.005}, abstractNote={Most animals are concurrently infected with multiple parasite species and live in environments with fluctuating resource availability. Resource limitation can influence host immune responses and the degree of competition between co-infecting parasites, yet its effects on individual health and pathogen transmission have not been studied for co-infected hosts. To test how resource limitation affects immune trade-offs and co-infection outcomes, we conducted a factorial experiment using laboratory mice. Mice were given a standard or low protein diet, dosed with two species of helminths (alone and in combination), and then challenged with a microparasite. Using a community ecology trophic framework, we found that co-infection influenced parasite survival and reproduction via host immunity, but the magnitude and direction of responses depended on resources and the combination of co-infecting parasites. Our findings highlight that resources and their consequence for host defenses are a key context that shapes the magnitude and direction of parasite interactions.}, number={7}, journal={International Journal for Parasitology}, publisher={Elsevier BV}, author={Budischak, SA and Sakamoto, K and Megow, LC and Cummings, KR and Urban, JF and Ezenwa, VO}, year={2015}, month={Jun}, pages={455–463} }
 @inproceedings{coulson_bowdish_sakamoto_2015, title={Role of MARCO Scavenger Receptor in Resistance to Tuberculosis}, author={Coulson, G and Bowdish, D and Sakamoto, K}, year={2015}, month={Jan} }
 @article{phan_chen_xu_li_gao_foster_teng_tripp_sakamoto_he_2014, title={A respiratory syncytial virus (RSV) vaccine based on parainfluenza virus 5 (PIV5)}, volume={32}, DOI={10.1016/j.vaccine.2014.03.049}, abstractNote={Human respiratory syncytial virus (RSV) is a leading cause of severe respiratory disease and hospitalizations in infants and young children. It also causes significant morbidity and mortality in elderly and immune compromised individuals. No licensed vaccine currently exists. Parainfluenza virus 5 (PIV5) is a paramyxovirus that causes no known human illness and has been used as a platform for vector-based vaccine development. To evaluate the efficacy of PIV5 as a RSV vaccine vector, we generated two recombinant PIV5 viruses – one expressing the fusion (F) protein and the other expressing the attachment glycoprotein (G) of RSV strain A2 (RSV A2). The vaccine strains were used separately for single-dose vaccinations in BALB/c mice. The results showed that both vaccines induced RSV antigen-specific antibody responses, with IgG2a/IgG1 ratios similar to those seen in wild-type RSV A2 infection. After challenging the vaccinated mice with RSV A2, histopathology of lung sections showed that the vaccines did not exacerbate lung lesions relative to RSV A2-immunized mice. Importantly, both F and G vaccines induced protective immunity. Therefore, PIV5 presents an attractive platform for vector-based vaccines against RSV infection.}, number={25}, journal={Vaccine}, publisher={Elsevier BV}, author={Phan, SI and Chen, Z and Xu, P and Li, Z and Gao, X and Foster, SL and Teng, MN and Tripp, RA and Sakamoto, K and He, B}, year={2014}, month={May}, pages={3050–3057} }
 @article{palomares_sakamoto_hurley_walz_brock_2014, title={Acute infection with bovine viral diarrhea virus causes depletion of WC1+ ?d T cells in lymphoid tissues in beef calves}, publisher={Conference of Research Workers in Animal Diseases}, author={Palomares, RA and Sakamoto, K and Hurley, DJ and Walz, HL and Brock, KV}, editor={Ellis, JEditor}, year={2014}, month={Dec} }
 @article{lee_quan_kwon_sakamoto_kang_compans_moore_2014, title={Additive protection induced by mixed virus-like particles presenting respiratory syncytial virus fusion or attachment glycoproteins}, volume={111}, DOI={10.1016/j.antiviral.2014.09.005}, abstractNote={Respiratory syncytial virus (RSV) is the most important pathogen for lower respiratory tract illness in infants and a high priority for vaccine development. We previously reported that RSV virus-like particles (VLPs) expressing either the fusion (F) or attachment (G) glycoprotein could confer protection against RSV challenge in BALB/c mice. Here, we tested the hypothesis that RSV VLP vaccine efficacy can be enhanced by mixing RSV VLP F and RSV VLP G, and we analyzed host responses to these RSV VLPs. Mice were immunized with VLP F, VLP G, or VLP F + VLP G. Lung viral loads in BALB/c mice following RSV strain A2-line19F challenge were lower in mice vaccinated with RSV VLP F + VLP G compared to VLP F- or VLP G-vaccinated mice. Vaccination with VLP F or VLP F + VLP G induced similar levels of neutralizing antibodies. The enhanced protection against RSV challenge induced by vaccination with RSV VLP F + VLP G correlated with CD8 T cells producing T helper type 1 cytokines. VLP G vaccination alone followed by challenge resulted in immunopathology similar to formalin-inactivated RSV vaccination and RSV challenge. Taken together, mixed VLP F + VLP G provided a high level of protection against RSV without vaccine-induced immunopathology, but VLP G vaccination enhanced disease when used alone.}, journal={Antiviral Research}, publisher={Elsevier BV}, author={Lee, S and Quan, F-S and Kwon, Y and Sakamoto, K and Kang, S-M and Compans, RW and Moore, ML}, year={2014}, month={Nov}, pages={129–135} }
 @article{secrest_sakamoto_2014, title={HALO AND REVERSE HALO SIGNS IN CANINE PULMONARY COMPUTED TOMOGRAPHY}, volume={55}, DOI={10.1111/vru.12132}, abstractNote={The halo sign (HS) and reverse halo sign (RHS) are radiologic signs identified on pulmonary computed tomography (CT) in people. The HS is described as a circular area of ground‐glass attenuation surrounding a pulmonary nodule or mass. The RHS is defined as a focal, rounded area of ground‐glass attenuation surrounded by a more or less complete ring of consolidation. These signs have been identified in a variety of diseases in people. The purpose of this retrospective study was to determine if the HS and RHS occur in dogs with pulmonary disease and to determine if they are associated with a particular disease process. In addition, the appearance of the HS and RHS was correlated with the histopathologic changes. Our results indicate that the HS and RHS are not common signs identified in dogs with pulmonary disease with an HS noted in five cases and an RHS in 4 of the 33 dogs that met the inclusion criteria. An association between the HS ( P ‐value 0.8163) or RHS ( P ‐value 0.5988) and neoplasia, infectious/inflammatory, and other disease processes was not identified using a Fisher's exact test. The HS was identified in neoplastic, infectious, and inflammatory conditions, with the RHS identified in neoplastic and infectious diseases and a lung lobe torsion. Histologically, the HS and RHS were caused by tumor extension, necrosis, and/or hemorrhage of the pulmonary parenchyma.}, number={3}, journal={Veterinary Radiology and Ultrasound}, publisher={Wiley}, author={Secrest, S and Sakamoto, K}, year={2014}, month={May}, pages={272–277} }
 @article{hotard_lee_currier_crowe_sakamoto_newcomb_peebles_plemper_moore_2015, title={Identification of Residues in the Human Respiratory Syncytial Virus Fusion Protein That Modulate Fusion Activity and Pathogenesis}, volume={89}, DOI={10.1128/jvi.02472-14}, abstractNote={ABSTRACT Human respiratory syncytial virus (RSV) lower respiratory tract infection can result in inflammation and mucus plugging of airways. RSV strain A2-line19F induces relatively high viral load and mucus in mice. The line 19 fusion (F) protein harbors five unique residues compared to the non-mucus-inducing strains A2 and Long, at positions 79, 191, 357, 371, and 557. We hypothesized that differential fusion activity is a determinant of pathogenesis. In a cell-cell fusion assay, line 19 F was more fusogenic than Long F. We changed the residues unique to line 19 F to the corresponding residues in Long F and identified residues 79 and 191 together as responsible for high fusion activity. Surprisingly, mutation of residues 357 or 357 with 371 resulted in gain of fusion activity. Thus, we generated RSV F mutants with a range of defined fusion activity and engineered these into recombinant viruses. We found a clear, positive correlation between fusion activity and early viral load in mice; however, we did not detect a correlation between viral loads and levels of airway mucin expression. The F mutant with the highest fusion activity, A2-line19F-K357T/Y371N, induced high viral loads, severe lung histopathology, and weight loss but did not induce high levels of airway mucin expression. We defined residues 79/191 as critical for line 19 F fusion activity and 357/371 as playing a role in A2-line19F mucus induction. Defining the molecular basis of the role of RSV F in pathogenesis may aid vaccine and therapeutic strategies aimed at this protein. IMPORTANCE Human respiratory syncytial virus (RSV) is the most important lower respiratory tract pathogen of infants for which there is no vaccine. Elucidating mechanisms of RSV pathogenesis is important for rational vaccine and drug design. We defined specific amino acids in the fusion (F) protein of RSV strain line 19 critical for fusion activity and elucidated a correlation between fusion activity and viral load in mice. Further, we identified two distinct amino acids in F as contributing to the mucogenic phenotype of the A2-line19F virus. Taken together, these results illustrate a role for RSV F in virulence.}, number={1}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Hotard, AL and Lee, S and Currier, MG and Crowe, JE and Sakamoto, K and Newcomb, DC and Peebles, RS and Plemper, RK and Moore, ML}, editor={Lyles, DSEditor}, year={2015}, month={Jan}, pages={512–522} }
 @article{frontera-acevedo_sakamoto_2015, title={Local pulmonary immune responses in domestic cats naturally infected with Cytauxzoon felis}, volume={163}, DOI={10.1016/j.vetimm.2014.10.012}, abstractNote={Cytauxzoonosis is a hemoprotozoal disease of cats and wild felids in the South and Southeastern United States caused by Cytauxzoon felis. Although the causative agent has been recognized since the seventies, no study has examined the local immune response in affected organs, such as the lung, and compared them to the lungs of uninfected domestic cats. Previous studies have suggested that the histopathologic findings in the lungs of C. felis-infected cats are caused by the release of pro-inflammatory mediators, such as cytokines and increased production of inducible nitric oxide synthase (iNOS), by the infected macrophages. Our laboratory had previously found an upregulation of the adhesion molecule CD18, which can stimulate the release of these pro-inflammatory mediators. The objective of this study was to characterize local pulmonary immune responses in cats naturally infected with C. felis. Immunohistochemistry was performed to detect tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, iNOS, and major histocompatibility complex (MHC) II in 19 lungs from affected cats that died between 2005 and 2013. Results showed increased expression of all of these molecules when compared to lungs from uninfected, healthy cats. Furthermore, MHC II is expressed in the endothelium of C. felis naturally infected cats. These results support that there is a marked, local, pro-inflammatory immune response that can contribute to the pathogenesis of cytauxzoonosis in the lungs.}, number={1-2}, journal={Veterinary Immunology and Immunopathology}, publisher={Elsevier BV}, author={Frontera-Acevedo, K and Sakamoto, K}, year={2015}, month={Jan}, pages={1–7} }
 @inproceedings{wong_boyce_elsmo_jenkins_howerth_phillips_sanchez_sakamoto_2014, title={Outbreak of Burkholderia cenocepacia as a Cause of Suppurative Cellulitis in Five Cats}, author={Wong, J and Boyce, L and Elsmo, E and Jenkins, T and Howerth, E and Phillips, A and Sanchez, S and Sakamoto, K}, year={2014}, month={Nov} }
 @misc{coulson_bowdish_sakamoto_2014, title={Role of MARCO Scavenger Receptor in Resistance to TB}, author={Coulson, G and Bowdish, DME and Sakamoto, K}, year={2014}, month={Jan} }
 @misc{budischak_sakamoto_urban_ezenwa_2013, title={Causes and Consequences of Parasite Community Composition}, author={Budischak, S and Sakamoto, K and Urban, J and Ezenwa, V}, year={2013}, month={Mar} }
 @misc{moore_burkman_garner_sakamoto_moorhead_2013, title={Determination of Host Factors Required for Infection of the Domestic Cat with the Human Parasite, Brugia malayi}, author={Moore, ZT and Burkman, EJ and Garner, B and Sakamoto, K and Moorhead, AR}, year={2013}, month={Oct} }
 @inproceedings{moore_burkman_garner_sakamoto_moorhead_2013, title={Determination of Host Factors Required for Infection of the Domestic Cat with the Human Parasite, Brugia malayi}, author={Moore, ZT and Burkman, EJ and Garner, B and Sakamoto, K and Moorhead, AR}, year={2013}, month={Aug} }
 @article{bowdish_sakamoto_lack_hill_sirugo_newport_gordon_hill_vannberg_2013, title={Genetic variants of MARCO are associated with susceptibility to pulmonary tuberculosis in a Gambian population}, volume={14}, DOI={10.1186/1471-2350-14-47}, abstractNote={The two major class A scavenger receptors are scavenger receptor A (SRA), which is constitutively expressed on most macrophage populations, and macrophage receptor with collagenous structure (MARCO), which is constitutively expressed on a more restricted subset of macrophages, (e.g. alveolar macrophages) but whose expression increases on most macrophages during the course of infection. Although the primary role of SRA appears to be clearance of modified host proteins and lipids, mice defective in expression of either MARCO or SRA are immunocompromised in multiple models of infection and in vitro assays, the scavenger receptors have been demonstrated to bind bacteria and to enhance pro-inflammatory signalling to many bacterial lung pathogens; however their importance in Mycobacterium tuberculosis infection, is less clear. To determine whether polymorphisms in either SRA or MARCO were associated with tuberculosis, a case–control study of was performed. DNA samples from newly-detected, smear-positive, pulmonary tuberculosis cases were collected from The Gambia. Controls for this study consisted of DNA from cord bloods obtained from routine births at local Gambian health clinics. Informed written consent was obtained from patients or their parents or guardians. Ethical approval was provided by the joint The Gambian Government/MRC Joint Ethics Committee. We studied the frequencies of 25 polymorphisms of MSR1 (SRA) and 22 in MARCO in individuals with tuberculosis (n=1284) and matched controls (n=1349). No SNPs within the gene encoding or within 1 kb of the promoter sequence of MSR1 were associated with either susceptibility or resistance to tuberculosis. Three SNPs in MARCO (rs4491733, Mantel-Haenszel 2x2 χ2 = 6.5, p = 0.001, rs12998782, Mantel-Haenszel 2x2 χ2 = 6.59, p = 0.001, rs13389814 Mantel-Haenszel 2x2 χ2 = 6.9, p = 0.0009) were associated with susceptibility to tuberculosis and one (rs7559955, Mantel-Haenszel 2x2 χ2 = 6.9, p = 0.0009) was associated with resistance to tuberculosis. These findings identify MARCO as a potentially important receptor in the host response to tuberculosis.}, number={1}, journal={BMC Medical Genetics}, publisher={Springer Science and Business Media LLC}, author={Bowdish, DME and Sakamoto, K and Lack, NA and Hill, PC and Sirugo, G and Newport, MJ and Gordon, S and Hill, AVS and Vannberg, FO}, year={2013}, month={Dec} }
 @article{xu_huang_gao_michel_hirsch_hogan_sakamoto_ho_wu_he_2013, title={Infection of Mice, Ferrets, and Rhesus Macaques with a Clinical Mumps Virus Isolate}, volume={87}, DOI={10.1128/jvi.01028-13}, abstractNote={ABSTRACT In recent years, many mumps outbreaks have occurred in vaccinated populations worldwide. The reasons for these outbreaks are not clear. Animal models are needed to investigate the causes of outbreaks and to understand the pathogenesis of mumps virus (MuV). In this study, we have examined the infection of three animal models with an isolate of mumps virus from a recent outbreak (MuV-IA). We have found that while both ferrets and mice generated humoral and cellular immune responses to MuV-IA infection, no obvious signs of illness were observed in these animals; rhesus macaques were the most susceptible to MuV-IA infection. Infection of rhesus macaques via both intranasal and intratracheal routes with MuV-IA led to the typical clinical signs of mumps 2 weeks to 4 weeks postinfection. However, none of the infected macaques showed any fever or neurologic signs during the experimental period. Mumps viral antigen was detected in parotid glands by immunohistochemistry (IHC). Rhesus macaques represent the best animal model for the study of mumps virus pathogenesis.}, number={14}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Xu, P and Huang, Z and Gao, X and Michel, FJ and Hirsch, G and Hogan, RJ and Sakamoto, K and Ho, W and Wu, J and He, B}, year={2013}, month={Jul}, pages={8158–8168} }
 @inproceedings{frontera-acevedo_sakamoto_2013, title={Local Pulmonary Immune Responses in Cytauxzoon felis-infected Domestic Cats}, author={Frontera-Acevedo, K and Sakamoto, K}, year={2013}, month={Nov} }
 @misc{comolli_olsen_schnellbacher_seguel_sakamoto_divers_2013, title={Malignant Epithelial Neoplasm in a Wild Black Rat Snake}, author={Comolli, J and Olsen, H and Schnellbacher, R and Seguel, M and Sakamoto, K and Divers, S}, year={2013}, month={Oct} }
 @inproceedings{edwards_williamson_garner_storey_sakamoto_2013, title={Pathology of Haemonchus contortus in New World Camelids in Georgia: A Retrospective Study}, author={Edwards, E and Williamson, L and Garner, B and Storey, B and Sakamoto, K}, year={2013}, month={Nov} }
 @inproceedings{edwards_williamson_garner_storey_sakamoto_2013, title={Pathology of Haemonchus contortus in New World Camelids in Georgia: A Retrospective Study}, author={Edwards, EE and Williamson, LH and Garner, B and Storey, B and Sakamoto, K}, year={2013}, month={Oct} }
 @misc{budischak_sakamoto_urban_ezenwa_2013, title={Resource Limitation Alters the Consequences of Coinfection for Both Hosts and Parasites}, author={Budischak, S and Sakamoto, K and Urban, J and Ezenwa, V}, year={2013}, month={Mar} }
 @article{watson_murdock_cazzini_schnellbacher_divers_sakamoto_2013, title={Retrobulbar adenocarcinoma in an Amazon parrot (<i>Amazona autumnalis</i>)}, volume={25}, DOI={10.1177/1040638712474817}, abstractNote={Retrobulbar neoplasms are not common in mammals and are even more infrequently seen in nonmammalian species. The current report describes a retrobulbar mass creating exophthalmia and neurologic signs in a red-lored Amazon parrot ( Amazona autumnalis). A 27-year-old female parrot presented for a 3-day history of anorexia and a 2-week history of periocular soft tissue swelling and exophthalmia of the right eye. Physical examination revealed 9% dehydration and right eye exophthalmia with inability to retropulse the globe. A fine-needle aspirate was performed, and cytologic evaluation revealed necrotic debris with scattered clusters of epithelial cells, moderate numbers of macrophages, and few heterophils. Given the possibility of neoplasia and paucity of treatment options, the owners elected euthanasia and submitted the body for necropsy. A large, fluctuant, friable, red, retrobulbar mass with multiple areas of hemorrhage, on cut surface, was noted at necropsy. Histologically, the mass was composed of neoplastic, cuboidal to columnar epithelial cells, forming rosette-like glandular structures, admixed with abundant necrotic debris. The neoplastic cells were strongly positive for cytokeratin (AE1/AE3) by immunohistochemistry. Based on histopathology and immunohistochemistry, the mass was diagnosed as an adenocarcinoma.}, number={2}, journal={Journal of Veterinary Diagnostic Investigation}, publisher={SAGE Publications}, author={Watson, VE and Murdock, JH and Cazzini, P and Schnellbacher, R and Divers, SJ and Sakamoto, K}, year={2013}, month={Mar}, pages={273–276} }
 @misc{coulson_sakamoto_2013, title={Role of MARCO Scavenger Receptor in Tuberculosis}, author={Coulson, G and Sakamoto, K}, year={2013}, month={Nov} }
 @article{frontera-acevedo_balsone_dugan_makemson_sellers_brown_peterson_creevy_garner_sakamoto_2013, title={Systemic immune responses in Cytauxzoon felis-infected domestic cats}, volume={74}, DOI={10.2460/ajvr.74.6.901}, abstractNote={To characterize systemic immune responses in Cytauxzoon felis-infected cats.Blood and lung samples obtained from 27 cats.Cats were allocated into 4 groups: cats that died of cytauxzoonosis, acutely ill C felis-infected cats, healthy survivors of C felis infection, and healthy uninfected cats. Serum concentrations of tumor necrosis factor-α and interleukin-1 β were measured and serum proteins characterized. Blood smears were stained immunocytochemically and used to assess immunoglobulin deposition. Immunohistochemical expression of CD18 and tumor necrosis factor-α were compared in lung tissues obtained from cats that died and healthy uninfected cats. A real-time reverse-transcription PCR assay for CD18 expression was performed on selected blood samples from all groups.Concentrations of both cytokines were greater and serum albumin concentrations were significantly lower in cats that died of cytauxzoonosis, compared with results for all other groups. Erythrocytes from acutely ill cats and survivors of C felis infection had staining for plasmalemmal IgM, whereas erythrocytes from the other groups did not. Increased staining of C felis-infected monocytes and interstitial neutrophils for CD18 was detected. The real-time reverse-transcription PCR assay confirmed a relative increase in CD18 expression in cats that died of cytauxzoonosis and acutely ill cats, compared with expression in other groups. Immunostaining for TNF-α in lung samples confirmed a local proinflammatory response.Results indicated immunopathologic responses were greater in cats that died of C felis infection than in cats that survived C felis infection.}, number={6}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Frontera-Acevedo, K and Balsone, NM and Dugan, MA and Makemson, CR and Sellers, LB and Brown, HM and Peterson, DS and Creevy, KE and Garner, BC and Sakamoto, K}, year={2013}, month={Jun}, pages={901–909} }
 @article{li_xu_chen_gao_wang_basler_sakamoto_he_2013, title={The L Gene of J Paramyxovirus Plays a Critical Role in Viral Pathogenesis}, volume={87}, DOI={10.1128/jvi.02039-13}, abstractNote={J paramyxovirus (JPV) was first isolated from moribund mice with hemorrhagic lung lesions in Australia in the 1970s. Recent sequencing of JPV (JPV-LW) confirms that JPV is a paramyxovirus with several unique features. However, neither JPV-LW nor a recombinant JPV based on its sequence (rJPV-LW) caused obvious illness in mice. In this work, we analyzed a different JPV isolate (JPV-BH), which behaved differently from JPV-LW; JPV-BH grew more slowly in Vero cells and had less of a cytopathic effect on tissue culture cells but caused severe disease in mice. We have determined the whole genome sequence of JPV-BH. There were several nucleotide sequence differences between JPV-BH and JPV-LW, one in the leader sequence, one in the GX gene, and three in the L gene. The high sequence identity between JPV-BH and JPV-LW suggests that JPV-BH and JPV-LW are the same virus strain but were obtained at different passages from different laboratories. To understand the roles of these nucleotide sequence differences in pathogenicity in mice, we generated a recombinant JPV-BH strain (rJPV-BH) and hybrid rJPV-BH strains with sequences from the leader sequence (rJPV-BH-Le-LW), the GX gene (rJPV-BH-GX-LW), and the L gene (rJPV-BH-L-LW) of JPV-LW and compared their pathogenicities in mice. We have found that rJPV-BH-L-LW was attenuated in mice, indicating that nucleotide sequence differences in the L gene play a critical role in pathogenesis.}, number={23}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Li, Z and Xu, J and Chen, Z and Gao, X and Wang, L-F and Basler, C and Sakamoto, K and He, B}, year={2013}, month={Dec}, pages={12990–12998} }
 @article{stokes_currier_sakamoto_lee_collins_plemper_moore_2013, title={The Respiratory Syncytial Virus Fusion Protein and Neutrophils Mediate the Airway Mucin Response to Pathogenic Respiratory Syncytial Virus Infection}, volume={87}, DOI={10.1128/jvi.01347-13}, abstractNote={ABSTRACT Respiratory syncytial virus (RSV) is the leading cause of death due to a viral etiology in infants. RSV disease is characterized by epithelial desquamation, neutrophilic bronchiolitis and pneumonia, and obstructive pulmonary mucus. It has been shown that infection of BALB/cJ mice with RSV clinical isolate A2001/2-20 (2-20) results in a higher early viral load, greater airway necrosis, and higher levels of interleukin-13 (IL-13) and airway mucin expression than infection with RSV laboratory strain A2. We hypothesized that the fusion (F) protein of RSV 2-20 is a mucus-inducing viral factor. In vitro , the fusion activity of 2-20 F but not that of A2 F was enhanced by expression of RSV G. We generated a recombinant F-chimeric RSV by replacing the F gene of A2 with the F gene of 2-20, generating A2–2-20F. Similar to the results obtained with the parent 2-20 strain, infection of BALB/cJ mice with A2–2-20F resulted in a higher early viral load and higher levels of subsequent pulmonary mucin expression than infection with the A2 strain. A2–2-20F infection induced greater necrotic airway damage and neutrophil infiltration than A2 infection. We hypothesized that the neutrophil response to A2–2-20F infection is involved in mucin expression. Antibody-mediated depletion of neutrophils in RSV-infected mice resulted in lower tumor necrosis factor alpha levels, fewer IL-13-expressing CD4 T cells, and less airway mucin production in the lung. Our data are consistent with a model in which the F and attachment (G) glycoprotein functional interaction leads to enhanced fusion and F is a key factor in airway epithelium infection, pathogenesis, and subsequent airway mucin expression.}, number={18}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Stokes, KL and Currier, MG and Sakamoto, K and Lee, S and Collins, PL and Plemper, RK and Moore, ML}, year={2013}, month={Sep}, pages={10070–10082} }
 @misc{gupta_giri_sakamoto_sylte_quinn_watford_2013, title={The role of the serine-threonine kinase Tpl2 in host immunity to Mycobacterium tuberculosis}, publisher={University of Georgia}, author={Gupta, T and Giri, P and Sakamoto, K and Sylte, M and Quinn, F and Watford, W}, year={2013}, month={Mar} }
 @misc{alagappan_budischak_megow_bringuel_sellers_patel_kamau-nataki_zehner_urban_ezenwa_et al._2012, title={A Mouse Model of Dual Helminth and Mycobacterium bovis Co-infection}, author={Alagappan, J and Budischak, S and Megow, L and Bringuel, B and Sellers, L and Patel, N and Kamau-Nataki, O and Zehner, A and Urban, J and Ezenwa, V and et al.}, year={2012}, month={Aug} }
 @article{cherukuri_stokes_patton_kuo_sakamoto_lambert_stillman_moore_lee_2012, title={An adjuvanted respiratory syncytial virus fusion protein induces protection in aged BALB/c mice}, volume={9}, DOI={10.1186/1742-4933-9-21}, abstractNote={Respiratory Syncytial Virus (RSV) causes significant disease in the elderly, in part, because immunosenescence impairs protective immune responses to infection in this population. Despite previous and current efforts, there is no RSV vaccine currently licensed in infants or elderly adults. Adjuvanted RSV subunit vaccines have the potential to boost waning immune responses and reduce the burden of RSV disease in the elderly population.We used an aged BALB/c mouse model to evaluate immune responses to RSV Fusion (F) protein in the absence and presence of an alum adjuvant. We demonstrate that aged BALB/c mice immunized with alum-adjuvanted RSV F protein had significantly reduced lung viral titers at day 4 following challenge with wild-type (wt) RSV. Serum neutralizing antibody titers measured on day 27 correlated with protection in both young and aged vaccinated mice, although the magnitude of antibody titers was lower in aged mice. Unlike young mice, in aged mice, alum-adjuvanted RSV F did not induce lung TH2-type cytokines or eosinophil infiltration compared to non-adjuvanted F protein following wt RSV challenge.Our studies demonstrate that neutralizing anti-RSV antibody titers correlate with protection in both young and aged BALB/c mice vaccinated with RSV F protein vaccines. The F + alum formulation mediated greater protection compared to the non-adjuvanted F protein in both young and aged mice. However, while alum can boost F-specific antibody responses in aged mice, it does not completely overcome the reduced ability of a senescent immune system to respond to the RSV F antigen. Thus, our data suggest that a stronger adjuvant may be required for the prevention of RSV disease in immunosenescent populations, to achieve the appropriate balance of protective neutralizing antibodies and effective TH1-type cytokine response along with minimal lung immunopathology.}, number={1}, journal={Immunity and Ageing}, publisher={Springer Science and Business Media LLC}, author={Cherukuri, A and Stokes, KL and Patton, K and Kuo, H and Sakamoto, K and Lambert, S and Stillman, E and Moore, ML and Lee, S}, year={2012}, month={Dec} }
 @inproceedings{sakamoto_budischak_ezenwa_2012, title={Causes and Consequences of Parasite Community Composition}, author={Sakamoto, K and Budischak, S and Ezenwa, V}, year={2012}, month={Oct} }
 @misc{megow_budischak_bringuel_patel_cummings_kamau-nataki_sellers_ezenwa_sakamoto_2012, title={Effects of Helminth Infection on Local and Systemic Immunity}, author={Megow, L and Budischak, S and Bringuel, B and Patel, N and Cummings, K and Kamau-Nataki, O and Sellers, L and Ezenwa, V and Sakamoto, K}, year={2012}, month={Apr} }
 @misc{megow_budischak_bringuel_patel_cummings_kamau-nataki_sellers_ezenwa_sakamoto_2012, title={Effects of Helminth Infection on Local and Systemic Immunity}, author={Megow, L and Budischak, S and Bringuel, B and Patel, N and Cummings, K and Kamau-Nataki, O and Sellers, L and Ezenwa, V and Sakamoto, K}, year={2012}, month={Mar} }
 @misc{budischak_sakamoto_ezenwa_2012, title={Lab Experiments with Buffalo are a Bad Idea: Investigating Co-infection Interactions in a Model System}, author={Budischak, S and Sakamoto, K and Ezenwa, V}, year={2012}, month={Jan} }
 @article{rose_sakamoto_leifer_2012, title={Multifunctional role of dextran sulfate sodium for in vivo modeling of intestinal diseases}, volume={13}, DOI={10.1186/1471-2172-13-41}, abstractNote={Abstract Background Inflammatory bowel diseases (IBDs) are chronic, relapsing disorders that affect the gastrointestinal tract of millions of people and continue to increase in incidence each year. While several factors have been associated with development of IBDs, the exact etiology is unknown. Research using animal models of IBDs is beginning to provide insights into how the different factors contribute to disease development. Oral administration of dextran sulfate sodium (DSS) to mice induces a reproducible experimental colitis that models several intestinal lesions associated with IBDs. The murine DSS colitis model can also be adapted to quantify intestinal repair following injury. Understanding the mechanistic basis behind intestinal repair is critical to development of new therapeutics for IBDs because of their chronic relapsing nature. Results The murine DSS colitis model was adapted to provide a system enabling the quantification of severe intestinal injury with impaired wound healing or mild intestinal injury with rapid restoration of mucosal integrity, by altering DSS concentrations and including a recovery phase. We showed that through a novel format for presentation of the clinical disease data, the temporal progression of intestinal lesions can be quantified on an individual mouse basis. Additionally, parameters for quantification of DSS-induced alterations in epithelial cell populations are included to provide insights into mechanisms underlying the development of these lesions. For example, the use of the two different model systems showed that toll-like receptor 9, a nucleic acid-sensing pattern recognition receptor, is important for protection only following mild intestinal damage and suggests that this model is superior for identifying proteins necessary for intestinal repair. Conclusions We showed that using a murine DSS-induced experimental colitis model system, and presenting data in a longitudinal manner on a per mouse basis, enhanced the usefulness of this model, and provided novel insights into the role of an innate immune receptor in intestinal repair. By elucidating the mechanistic basis of intestinal injury and repair, we can begin to understand the etiology of IBDs, enabling development of novel therapeutics or prophylactics.}, number={1}, journal={BMC Immunology}, publisher={Springer Science and Business Media LLC}, author={Rose, WA and Sakamoto, K and Leifer, CA}, year={2012}, month={Dec} }
 @article{sakamoto_kim_rhoades_allavena_ehrt_wainwright_russell_rohde_2013, title={Mycobacterial Trehalose Dimycolate Reprograms Macrophage Global Gene Expression and Activates Matrix Metalloproteinases}, volume={81}, DOI={10.1128/iai.00906-12}, abstractNote={ABSTRACT Trehalose 6,6′-dimycolate (TDM) is a cell wall glycolipid and an important virulence factor of mycobacteria. In order to study the role of TDM in the innate immune response to Mycobacterium tuberculosis , microarray analysis was used to examine gene regulation in murine bone marrow-derived macrophages in response to 90-μm-diameter polystyrene microspheres coated with TDM. A large number of genes, particularly those involved in the immune response and macrophage function, were up- or downregulated in response to these TDM-coated beads compared to control beads. Genes involved in the immune response were specifically upregulated in a myeloid differentiation primary response gene 88 (MyD88)-dependent manner. The complexity of the transcriptional response also increased greatly between 2 and 24 h. Matrix metalloproteinases (MMPs) were significantly upregulated at both time points, and this was confirmed by quantitative real-time reverse transcription-PCR (RT-PCR). Using an in vivo Matrigel granuloma model, the presence and activity of MMP-9 were examined by immunohistochemistry and in situ zymography (ISZ), respectively. We found that TDM-coated beads induced MMP-9 expression and activity in Matrigel granulomas. Macrophages were primarily responsible for MMP-9 expression, as granulomas from neutrophil-depleted mice showed staining patterns similar to that for wild-type mice. The relevance of these observations to human disease is supported by the similar induction of MMP-9 in human caseous tuberculosis (TB) granulomas. Given that MMPs likely play an important role in both the construction and breakdown of tuberculous granulomas, our results suggest that TDM may drive MMP expression during TB pathogenesis.}, number={3}, journal={Infection and Immunity}, publisher={American Society for Microbiology}, author={Sakamoto, K and Kim, MJ and Rhoades, ER and Allavena, RE and Ehrt, S and Wainwright, HC and Russell, DG and Rohde, KH}, editor={McCormick, BAEditor}, year={2013}, month={Mar}, pages={764–776} }
 @misc{silva_sellers_patel_filha_camara_sakamoto_2012, title={Naphthoquinolone Derivatives as a New Class of Antimycobacterial Agent}, author={Silva, VA and Sellers, L and Patel, N and Filha, MJS and Camara, CA and Sakamoto, K}, year={2012}, month={Jan} }
 @article{aschenbroich_rech_sousa_carmichael_sakamoto_2012, title={Pathology in Practice}, volume={240}, DOI={10.2460/javma.240.2.159}, abstractNote={In May 2006, a 1-year-old 3.41-kg (7.50-lb) neutered male domestic shorthair cat was evaluated at a veterinary hospital in Georgia because of sudden onset of inappetence and lethargy. Clinical and Gross FindingsPhysical examination revealed icterus, tachycardia, tachypnea, and high rectal temperature (40.4°C [104.7°F]).A CBC and serum biochemical analysis revealed anemia (Hct, 24%; reference interval, 30% to}, number={2}, journal={Journal of the American Veterinary Medical Association}, publisher={AMER VETERINARY MEDICAL ASSOC}, author={Aschenbroich, SA and Rech, RR and Sousa, RS and Carmichael, KP and Sakamoto, K}, year={2012}, month={Jan}, pages={159–161} }
 @article{tlr9 is important for protection against intestinal damage and for intestinal repair_2012, volume={2}, DOI={10.1038/srep00574}, abstractNote={Toll-like receptors (TLRs) are innate receptors critical for host defense and play a role in normal biological processes. For example, host DNA, a TLR9 ligand, stimulates epithelial repair following skin wounding. TLR signaling also plays a crucial role in regulating intestinal homeostasis. We therefore asked whether TLR9 is important for intestinal wound repair using a dextran sulfate sodium (DSS)-induced intestinal damage and repair model. We showed that TLR9-deficient mice are more susceptible to DSS and exhibited delayed wound repair at both the clinical and histologic levels. TLR9-deficient mice showed reduced gene expression of hairy enhancer of split 1, an intestinal progenitor cell differentiation factor and vascular endothelial growth factor, a growth factor important for epithelial cell restitution. Therefore, we conclude that TLR stimulation may play a normal role in regulating intestinal homeostasis and could potentially be a novel therapeutic target to enhance intestinal wound repair in inflammatory bowel diseases.}, number={1}, journal={Scientific Reports}, publisher={Springer Science and Business Media LLC}, year={2012}, month={Aug} }
 @misc{sakamoto_vannberg_lack_hill_gordon_rodgers_sellers_bowdish_2012, title={The Macrophage Scavenger Receptor MARCO Contributes to Host Defense Against Tuberculosis}, author={Sakamoto, K and Vannberg, FO and Lack, NA and Hill, AVS and Gordon, S and Rodgers, A and Sellers, L and Bowdish, DME}, year={2012}, month={Jan} }
 @article{sakamoto_2012, title={The Pathology of <i>Mycobacterium tuberculosis</i> Infection}, volume={49}, DOI={10.1177/0300985811429313}, abstractNote={Mycobacterium tuberculosis is an old enemy of the human race, with evidence of infection observed as early as 5000 years ago. Although more host-restricted than Mycobacterium bovis, which can infect all warm-blooded vertebrates, M. tuberculosis can infect, and cause morbidity and mortality in, several veterinary species as well. As M. tuberculosis is one of the earliest described bacterial pathogens, the literature describing this organism is vast and overwhelming. This review strives to distill what is currently known about this bacterium and the disease it causes for the veterinary pathologist.}, number={3}, journal={Veterinary pathology}, publisher={SAGE Publications}, author={Sakamoto, K}, year={2012}, month={May}, pages={423–439} }
 @article{lee_stokes_currier_sakamoto_lukacs_celis_moore_2012, title={Vaccine-Elicited CD8
            <sup>+</sup>
            T Cells Protect against Respiratory Syncytial Virus Strain A2-Line19F-Induced Pathogenesis in BALB/c Mice}, volume={86}, DOI={10.1128/jvi.01770-12}, abstractNote={ABSTRACT CD8 + T cells may contribute to vaccines for respiratory syncytial virus (RSV). Compared to CD8 + T cells responding to RSV infection, vaccine-elicited anti-RSV CD8 + T cells are less well defined. We used a peptide vaccine to test the hypothesis that vaccine-elicited RSV-specific CD8 + T cells are protective against RSV pathogenesis. BALB/c mice were treated with a mixture (previously termed TriVax) of an M2 82-90 peptide representing an immunodominant CD8 epitope, the Toll-like receptor (TLR) agonist poly(I·C), and a costimulatory anti-CD40 antibody. TriVax vaccination induced potent effector anti-RSV CD8 + cytotoxic T lymphocytes (CTL). Mice were challenged with RSV strain A2-line19F, a model of RSV pathogenesis leading to airway mucin expression. Mice were protected against RSV infection and against RSV-induced airway mucin expression and cellular lung inflammation when challenged 6 days after vaccination. Compared to A2-line19F infection alone, TriVax vaccination followed by challenge resulted in effector CD8 + T cells with greater cytokine expression and the more rapid appearance of RSV-specific CD8 + T cells in the lung. When challenged 42 days after TriVax vaccination, memory CD8 + T cells were elicited with RSV-specific tetramer responses equivalent to TriVax-induced effector CD8 + T cells. These memory CD8 + T cells had lower cytokine expression than effector CD8 + T cells, and protection against A2-line19F was partial during the memory phase. We found that vaccine-elicited effector anti-RSV CD8 + T cells protected mice against RSV infection and pathogenesis, and waning protection correlated with reduced CD8 + T cell cytokine expression.}, number={23}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Lee, S and Stokes, KL and Currier, MG and Sakamoto, K and Lukacs, NW and Celis, E and Moore, ML}, year={2012}, month={Dec}, pages={13016–13024} }
 @article{mishra_kent_haley_platt_sakamoto_2012, title={Atypical meningeal granular cell tumor in a dog}, volume={24}, DOI={10.1177/1040638711425942}, abstractNote={A 10-year-old, female spayed Chihuahua dog was presented to the Veterinary Teaching Hospital at the University of Georgia for evaluation of seizures, abnormal mentation, and cervical pain of 2 months duration. On magnetic resonance imaging, there was generalized thickening of the meninges overlying the left cerebral hemisphere and along the falx cerebri. Despite symptomatic treatment, the dog remained neurologically affected. Consequently, the owners elected euthanasia. On gross examination, the meninges covering the left cerebral hemisphere were severely thickened and firmly adhered to the calvaria. On transverse section, the white matter of the left cerebral hemisphere was swollen, enlarged, and extended across the midline with resultant compression of the right cerebral hemisphere. Cytologic evaluation of an impression smear of the thickened meninges showed numerous large, spindloid to polygonal cells with abundant, amphophilic, vacuolated cytoplasm, present either in clusters or in individual cells. Histopathologic evaluation of the meninges revealed a poorly circumscribed and infiltrative, moderately cellular neoplasm, composed of vacuolated, spindloid to polygonal cells with marked anisocytosis and anisokaryosis, arranged in sheets, and occasionally separated by thick bands of connective tissue. Immunohistochemistry for vimentin revealed diffuse cytoplasmic staining of the neoplastic cells. Although the periodic acid-Schiff reaction was negative, ultrastructural findings showed numerous vesicles that were empty or that contained membranous or electron-dense material. Based on gross, microscopic, immunohistochemical, and ultrastructural changes, the meningeal neoplasm was diagnosed as an atypical granular cell tumor.}, number={1}, journal={Journal of Veterinary Diagnostic Investigation}, publisher={SAGE Publications}, author={Mishra, S and Kent, M and Haley, A and Platt, S and Sakamoto, K}, year={2012}, month={Jan}, pages={192–197} }
 @article{stokes_chi_sakamoto_newcomb_huckabee_lee_pretto_williams_peebles_moore_2011, title={BALB/c mouse model of RSV clinical isolate A2001/2-20 pathogenesis}, volume={186}, journal={Journal of Immunology}, publisher={AMER ASSOC IMMUNOLOGISTS}, author={Stokes, K and Chi, M and Sakamoto, K and Newcomb, D and Huckabee, M and Lee, S and Pretto, C and Williams, J and Peebles, R and Moore, M}, year={2011}, month={Apr} }
 @misc{cummings_bringuel_megow_sellers_ezenwa_budischak_moorhead_sakamoto_2011, title={Development of a Murine Model for Intestinal Helminth and Mycobacterium bovis Co-infection}, author={Cummings, K and Bringuel, B and Megow, L and Sellers, L and Ezenwa, V and Budischak, S and Moorhead, AR and Sakamoto, K}, year={2011}, month={Aug} }
 @inproceedings{ezenwa_budischak_moorhead_sakamoto_2011, title={Development of a murine model for intestinal helminth and Mycobacterium bovis co-infection.}, author={Ezenwa, V and Budischak, S and Moorhead, A and Sakamoto, K}, year={2011}, month={Oct} }
 @article{stokes_chi_sakamoto_newcomb_currier_huckabee_lee_goleniewska_pretto_williams_et al._2011, title={Differential Pathogenesis of Respiratory Syncytial Virus Clinical Isolates in BALB/c Mice}, volume={85}, DOI={10.1128/jvi.01693-10}, abstractNote={ABSTRACT Airway mucus is a hallmark of respiratory syncytial virus (RSV) lower respiratory tract illness. Laboratory RSV strains differentially induce airway mucus production in mice. Here, we tested the hypothesis that RSV strains differ in pathogenesis by screening six low-passage RSV clinical isolates for mucogenicity and virulence in BALB/cJ mice. The RSV clinical isolates induced variable disease severity, lung interleukin-13 (IL-13) levels, and gob-5 levels in BALB/cJ mice. We chose two of these clinical isolates for further study. Infection of BALB/cJ mice with RSV A2001/2-20 (2-20) resulted in greater disease severity, higher lung IL-13 levels, and higher lung gob-5 levels than infection with RSV strains A2, line 19, Long, and A2001/3-12 (3-12). Like the line 19 RSV strain, the 2-20 clinical isolate induced airway mucin expression in BALB/cJ mice. The 2-20 and 3-12 RSV clinical isolates had higher lung viral loads than laboratory RSV strains at 1 day postinfection (p.i.). This increased viral load correlated with higher viral antigen levels in the bronchiolar epithelium and greater histopathologic changes at 1 day p.i. The A2 RSV strain had the highest peak viral load at day 4 p.i. RSV 2-20 infection caused epithelial desquamation, bronchiolitis, airway hyperresponsiveness, and increased breathing effort in BALB/cJ mice. We found that RSV clinical isolates induce variable pathogenesis in mice, and we established a mouse model of clinical isolate strain-dependent RSV pathogenesis that recapitulates key features of RSV disease.}, number={12}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Stokes, KL and Chi, MH and Sakamoto, K and Newcomb, DC and Currier, MG and Huckabee, MM and Lee, S and Goleniewska, K and Pretto, C and Williams, JV and et al.}, year={2011}, month={Jun}, pages={5782–5793} }
 @misc{sakamoto_perpinan_susta_dobson_dong_2011, title={Reovirus Infection in an American Crow}, author={Sakamoto, K and Perpinan, D and Susta, L and Dobson, E and Dong, L}, year={2011}, month={Apr} }
 @article{sun_wu_cai_lin_sellers_sakamoto_he_peterson_2011, title={Synthesis and Biological Evaluation of Analogues of AKT (Protein Kinase B) Inhibitor-IV}, volume={54}, DOI={10.1021/jm100912b}, abstractNote={Inhibitors of the PI3-kinase/AKT (protein kinase B) pathway are under investigation as anticancer and antiviral agents. The benzimidazole derivative AKT inhibitor-IV (ChemBridge 5233705) affects this pathway and exhibits potent anticancer and antiviral activity. To probe its biological activity, we synthesized AKT inhibitor-IV and 21 analogues using a novel six-step route based on ZrCl4-catalyzed cyclization of 1,2-arylenediamines with α,β-unsaturated aldehydes. We examined effects on viability of HeLa carcinoma cells, viability of normal human cells (NHBE), replication of recombinant parainfluenza virus 5 (PIV5) in HeLa cells, and replication of the intracellular bacterium Mycobacterium fortuitum in HeLa cells. Replacement of the benzimidazole N-ethyl substitutent of AKT inhibitor-IV with N-hexyl and N-dodecyl groups enhanced antiviral activity and cytotoxicity against the cancer cell line, but these compounds showed substantially lower toxicity (from 6-fold to >20-fold) against NHBE cells and no effect on M. fortuitum, suggesting inhibition of one or more host protein(s) required for proliferation of cancer cells and PIV5. The key structural elements identified here may facilitate identification of targets of this highly biologically active scaffold.}, number={5}, journal={Journal of Medicinal Chemistry}, publisher={American Chemical Society (ACS)}, author={Sun, Q and Wu, R and Cai, S and Lin, Y and Sellers, L and Sakamoto, K and He, B and Peterson, BR}, year={2011}, month={Mar}, pages={1126–1139} }
 @inproceedings{frontera-acevedo_balsone_dugan_makemson_creevy_peterson_brown_garner_sakamoto_2011, title={Systemic Immune Responses in Cytauxzoon felis-infected Domestic Cats}, author={Frontera-Acevedo, K and Balsone, N and Dugan, M and Makemson, C and Creevy, K and Peterson, DS and Brown, HM and Garner, BC and Sakamoto, K}, year={2011}, month={Oct} }
 @misc{frontera-acevedo_sellers_sakamoto_2011, title={The Sakamoto Laboratory: Immunopathology of Intrahistiocytic Pathogens}, author={Frontera-Acevedo, K and Sellers, L and Sakamoto, K}, year={2011}, month={Apr} }
 @misc{balsone_frontera-acevedo_moorhead_peterson_sellers_sakamoto_2010, title={Development of Reagents and Cell Lines in the Study of Feline Cytauxzoonosis}, author={Balsone, N and Frontera-Acevedo, K and Moorhead, AR and Peterson, DS and Sellers, L and Sakamoto, K}, year={2010}, month={Aug} }
 @article{li_xu_patel_fuentes_lin_anderson_sakamoto_wang_he_2011, title={Function of the Small Hydrophobic Protein of J Paramyxovirus}, volume={85}, DOI={10.1128/jvi.01673-10}, abstractNote={ABSTRACT At 18,954 nucleotides, the J paramyxovirus (JPV) genome is one of the largest in the family Paramyxoviridae , consisting of eight genes in the order 3′-N-P/V/C-M-F-SH-TM-G-L-5′. To study the function of novel paramyxovirus genes in JPV, a plasmid containing a full-length cDNA clone of the genome of JPV was constructed. In this study, the function of the small hydrophobic (SH) protein of JPV was examined by generating a recombinant JPV lacking the coding sequence of the SH protein (rJPVΔSH). rJPVΔSH was viable and had no growth defect in tissue culture cells. However, more tumor necrosis factor alpha (TNF-α) was produced during rJPVΔSH infection, suggesting that SH plays a role in inhibiting TNF-α production. rJPVΔSH induced more apoptosis in tissue culture cells than rJPV. Virus-induced apoptosis was inhibited by neutralizing antibody against TNF-α, suggesting that TNF-α contributes to JPV-induced apoptosis in vitro . The expression of JPV SH protein inhibited TNF-α-induced NF-κB activation in a reporter gene assay, suggesting that JPV SH protein can inhibit TNF-α signaling in vitro . Furthermore, infection of mice with rJPVΔSH induced more TNF-α expression, indicating that SH plays a role in blocking TNF-α expression in vivo .}, number={1}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Li, Z and Xu, J and Patel, J and Fuentes, S and Lin, Y and Anderson, D and Sakamoto, K and Wang, L-F and He, B}, year={2011}, month={Jan}, pages={32–42} }
 @article{camus_austel_woolums_stone_tennent-brown_sakamoto_2010, title={Pathology in Practice}, volume={237}, DOI={10.2460/javma.237.9.1041}, abstractNote={A 3-year-old approximately 450-kg (990-lb) Quarter Horse gelding was referred to the University of Georgia' s Large Animal Teaching Hospital because of fever, signs of depression, inappetence, extensive alopecia, and crusting of the skin of 1 month' s duration.One month prior to referral, crusts and marked edema of the lower portions of the horse' s limbs were evident.Cytologic examination of the moist underside of crusts taken from the skin of the lower aspects of the limbs performed at that time revealed infection with Dermatophilus congolensis.Appropriate systemic and topical treatments with antimicrobials, along with administration of NSAIDs, did not resolve the dermal lesions and had no influence on the horse' s other clinical signs.The dermal lesions spread over the horse' s entire body and onto the head during that treatment period.Subsequent IM injections of isoflupredone acetate (10 to 20 mg) given every 5 to 7}, number={9}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Camus, MS and Austel, MG and Woolums, AR and Stone, CA and Tennent-Brown, BS and Sakamoto, K}, year={2010}, month={Nov}, pages={1041–1043} }
 @misc{frontera-acevedo_sellers_sakamoto_2010, title={The Sakamoto Laboratory: Immunopathology of Intrahistiocytic Pathogens}, author={Frontera-Acevedo, K and Sellers, L and Sakamoto, K}, year={2010}, month={Jun} }
 @inbook{sakamoto_2010, place={Kidlington, UK}, title={Toxicologic Pathology of the Gastrointestinal Tract}, volume={10}, booktitle={Compre-hensive Toxicology}, publisher={Elsevier Ltd}, author={Sakamoto, Kaori}, editor={Hooser, S.Editor}, year={2010} }
 @article{sakamoto_geisel_kim_wyatt_sellers_smiley_cooper_russell_rhoades_2010, title={Fibrinogen Regulates the Cytotoxicity of Mycobacterial Trehalose Dimycolate but Is Not Required for Cell Recruitment, Cytokine Response, or Control of Mycobacterial Infection}, volume={78}, DOI={10.1128/iai.00451-09}, abstractNote={ABSTRACT During inflammatory responses and wound healing, the conversion of soluble fibrinogen to fibrin, an insoluble extracellular matrix, long has been assumed to create a scaffold for the migration of leukocytes and fibroblasts. Previous studies concluded that fibrinogen is a necessary cofactor for mycobacterial trehalose 6,6′-dimycolate-induced responses, because trehalose dimycolate-coated beads, to which fibrinogen was adsorbed, were more inflammatory than those to which other plasma proteins were adsorbed. Herein, we investigate roles for fibrin(ogen) in an in vivo model of mycobacterial granuloma formation and in infection with Mycobacterium tuberculosis , the causative agent of tuberculosis. In wild-type mice, the subcutaneous injection of trehalose dimycolate-coated polystyrene microspheres, suspended within Matrigel, elicited a pyogranulomatous response during the course of 12 days. In fibrinogen-deficient mice, neutrophils were recruited but a more suppurative lesion developed, with the marked degradation and disintegration of the matrix. Compared to that in wild-type mice, the early formation of granulation tissue in fibrinogen-deficient mice was edematous, hypocellular, and disorganized. These deficiencies were complemented by the addition of exogenous fibrinogen. The absence of fibrinogen had no effect on cell recruitment or cytokine production in response to trehalose dimycolate, nor was there a difference in lung histopathology or overall bacterial burden in mice infected with Mycobacterium tuberculosis . In this model, fibrin(ogen) was not required for cell recruitment, cytokine response, or response to infection, but it promoted granulation tissue formation and suppressed leukocyte necrosis.}, number={3}, journal={Infection and Immunity}, publisher={American Society for Microbiology}, author={Sakamoto, K and Geisel, RE and Kim, M-J and Wyatt, BT and Sellers, LB and Smiley, ST and Cooper, AM and Russell, DG and Rhoades, ER}, year={2010}, month={Mar}, pages={1004–1011} }
 @article{bowdish_sakamoto_kim_kroos_mukhopadhyay_leifer_tryggvason_gordon_russell_2009, title={MARCO, TLR2, and CD14 Are Required for Macrophage Cytokine Responses to Mycobacterial Trehalose Dimycolate and Mycobacterium tuberculosis}, volume={5}, DOI={10.1371/journal.ppat.1000474}, abstractNote={Virtually all of the elements of Mycobacterium tuberculosis (Mtb) pathogenesis, including pro-inflammatory cytokine production, granuloma formation, cachexia, and mortality, can be induced by its predominant cell wall glycolipid, trehalose 6,6′-dimycolate (TDM/cord factor). TDM mediates these potent inflammatory responses via interactions with macrophages both in vitro and in vivo in a myeloid differentiation factor 88 (MyD88)-dependent manner via phosphorylation of the mitogen activated protein kinases (MAPKs), implying involvement of toll-like receptors (TLRs). However, specific TLRs or binding receptors for TDM have yet to be identified. Herein, we demonstrate that the macrophage receptor with collagenous structure (MARCO), a class A scavenger receptor, is utilized preferentially to “tether” TDM to the macrophage and to activate the TLR2 signaling pathway. TDM-induced signaling, as measured by a nuclear factor-kappa B (NF-κB)-luciferase reporter assay, required MARCO in addition to TLR2 and CD14. MARCO was used preferentially over the highly homologous scavenger receptor class A (SRA), which required TLR2 and TLR4, as well as their respective accessory molecules, in order for a slight increase in NF-κB signaling to occur. Consistent with these observations, macrophages from MARCO−/− or MARCO−/−SRA−/− mice are defective in activation of extracellular signal-related kinase 1/2 (ERK1/2) and subsequent pro-inflammatory cytokine production in response to TDM. These results show that MARCO-expressing macrophages secrete pro-inflammatory cytokines in response to TDM by cooperation between MARCO and TLR2/CD14, whereas other macrophage subtypes (e.g. bone marrow–derived) may rely somewhat less effectively on SRA, TLR2/CD14, and TLR4/MD2. Macrophages from MARCO−/− mice also produce markedly lower levels of pro-inflammatory cytokines in response to infection with virulent Mtb. These observations identify the scavenger receptors as essential binding receptors for TDM, explain the differential response to TDM of various macrophage populations, which differ in their expression of the scavenger receptors, and identify MARCO as a novel component required for TLR signaling.}, number={6}, journal={PLoS Pathogens}, publisher={Public Library of Science (PLoS)}, author={Bowdish, DME and Sakamoto, K and Kim, M-J and Kroos, M and Mukhopadhyay, S and Leifer, CA and Tryggvason, K and Gordon, S and Russell, DG}, editor={Ramakrishnan, LEditor}, year={2009}, month={Jun}, pages={e1000474–e1000474} }
 @misc{dugan_frontera-acevedo_sellers_sakamoto_2009, title={The Potential Role of the Adhesion Molecule CD18 in Cytauxzoonosis Pathogenesis}, author={Dugan, M and Frontera-Acevedo, K and Sellers, L and Sakamoto, K}, year={2009}, month={Aug} }
 @misc{sakamoto_2008, title={Immunomodulation by Mycobacterial Cell Wall Lipids}, author={Sakamoto, K}, year={2008}, month={Sep} }
 @article{walle_sakamoto_osterrieder_2008, title={CCL3 and Viral Chemokine-Binding Protein gG Modulate Pulmonary Inflammation and Virus Replication during Equine Herpesvirus 1 Infection}, volume={82}, DOI={10.1128/jvi.02137-07}, abstractNote={ABSTRACT CCL3 is a proinflammatory chemokine that mediates many of the cellular changes occurring in pulmonary disease. Here, CCL3 −/− mice were used to investigate the role of this chemokine during respiratory herpesvirus infection. Compared to wild-type mice, CCL3 −/− mice infected with the alphaherpesvirus equine herpesvirus 1 (EHV-1) displayed reduced body weight loss but had higher pulmonary viral loads. Lungs from infected CCL3 −/− mice suffered a milder interstitial pneumonia, and fewer immune cells were recovered from the pulmonary airways after infection. We could also demonstrate that herpesvirus-encoded chemokine-binding glycoprotein G (gG) was capable of inhibiting the chemotactic functions of CCL3. This CCL3-mediated chemotaxis, however, was restored in the presence of gG-specific antibodies, which puts into question the advertised use of gG deletion mutants as marker vaccines. In summary, we concluded that CCL3 is a major player in controlling herpesvirus replication in the target organ, the lung, and does so by evoking a strong inflammatory response. The immunomodulatory activity of CCL3 is balanced by the expression of viral gG, whose chemokine-binding activity is mitigated in secondary infections by the production of anti-gG antibodies.}, number={4}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Walle, GR and Sakamoto, K and Osterrieder, N}, year={2008}, month={Feb}, pages={1714–1722} }
 @article{khader_pearl_sakamoto_gilmartin_bell_jelley-gibbs_ghilardi_desauvage_cooper_2005, title={IL-23 Compensates for the Absence of IL-12p70 and Is Essential for the IL-17 Response during Tuberculosis but Is Dispensable for Protection and Antigen-Specific IFN-γ Responses if IL-12p70 Is Available}, volume={175}, DOI={10.4049/jimmunol.175.2.788}, abstractNote={Abstract IL-12p70 induced IFN-γ is required to control Mycobacterium tuberculosis growth; however, in the absence of IL-12p70, an IL-12p40-dependent pathway mediates induction of IFN-γ and initial bacteriostatic activity. IL-23 is an IL-12p40-dependent cytokine containing an IL-12p40 subunit covalently bound to a p19 subunit that is implicated in the induction of CD4 T cells associated with autoimmunity and inflammation. We show that in IL-23 p19-deficient mice, mycobacterial growth is controlled, and there is no diminution in either the number of IFN-γ-producing Ag-specific CD4 T cells or local IFN-γ mRNA expression. Conversely, there is an almost total loss of both IL-17-producing Ag-specific CD4 T cells and local production of IL-17 mRNA in these mice. The absence of IL-17 does not alter expression of the antimycobacterial genes, NO synthase 2 and LRG-47, and the absence of IL-23 or IL-17, both of which are implicated in mediating inflammation, fails to substantially affect the granulomatous response to M. tuberculosis infection of the lung. Despite this redundancy, IL-23 is required to provide a moderate level of protection in the absence of IL-12p70, and this protection correlates with a requirement for IL-23 in the IL-12p70-independent induction of Ag-specific, IFN-γ-producing CD4 T cells. We also show that IL-23 is required for the induction of an IL-17-producing Ag-specific phenotype in naive CD4 T cells in vitro and that absence of IL-12p70 promotes an increase in the number of IL-17-producing Ag-specific CD4 T cells both in vitro and in vivo.}, number={2}, journal={Journal of Immunology}, publisher={The American Association of Immunologists}, author={Khader, SA and Pearl, JE and Sakamoto, K and Gilmartin, L and Bell, GK and Jelley-Gibbs, DM and Ghilardi, N and deSauvage, F and Cooper, AM}, year={2005}, month={Jul}, pages={788–795} }
 @article{geisel_sakamoto_russell_rhoades_2005, title={In Vivo Activity of Released Cell Wall Lipids of<i>Mycobacterium bovis</i>Bacillus Calmette-Guérin Is Due Principally to Trehalose Mycolates}, volume={174}, DOI={10.4049/jimmunol.174.8.5007}, abstractNote={Abstract The hallmark of Mycobacterium-induced pathology is granulomatous inflammation at the site of infection. Mycobacterial lipids are potent immunomodulators that contribute to the granulomatous response and are released in appreciable quantities by intracellular bacilli. Previously we investigated the granulomagenic nature of the peripheral cell wall lipids of Mycobacterium bovis bacillus Calmette-Guérin (BCG) by coating the lipids onto 90-μm diameter microspheres that were mixed into Matrigel matrix with syngeneic bone marrow-derived macrophages and injected i.p. into mice. These studies demonstrated that BCG lipids elicit proinflammatory cytokines and recruit leukocytes. In the current study we determined the lipids responsible for this proinflammatory effect. BCG-derived cell wall lipids were fractionated and purified by liquid chromatography and preparative TLC. The isolated fractions including phosphatidylinositol dimannosides, cardiolipin, phosphatidylglycerol, phosphatidylethanolamine, trehalose monomycolate, trehalose dimycolate, and mycoside B. Trehalose dimycolate, when delivered to bone marrow-derived murine macrophages, induced the greatest secretion of IL-1β, IL-6, and TNF-α in vitro. Trehalose dimycolate similarly induced the greatest secretion of these proinflammatory cytokines in ex vivo matrices over the course of 12 days. Trehalose monomycolate and dimycolate also induced profound neutrophil recruitment in vivo. Experiments with TLR2 or TLR4 gene-deficient mice revealed no defects in responses to trehalose mycolates, although MyD88-deficient mice manifested significantly reduced cell recruitment and cytokine production. These results demonstrate that the trehalose mycolates, particularly trehalose dimycolate, are the most bioactive lipids in the BCG extract, inducing a proinflammatory cascade that influences granuloma formation.}, number={8}, journal={Journal of Immunology}, publisher={The American Association of Immunologists}, author={Geisel, RE and Sakamoto, K and Russell, DG and Rhoades, ER}, year={2005}, month={Apr}, pages={5007–5015} }
 @misc{sakamoto_geisel_rhoades_rohde_russell_2004, title={Effect of Mode of Presentation on Macrophage Response to Trehalose Dimycolate}, author={Sakamoto, K and Geisel, RE and Rhoades, ER and Rohde, KH and Russell, DG}, year={2004}, month={Nov} }
 @article{sakamoto_kiupel_frank_march_2004, title={Vertebral Malformation, Syringomyelia, and Ventricular Septal Defect in a Dromedary Camel (<i>Camelius Dromedarius</i>)}, volume={16}, DOI={10.1177/104063870401600415}, abstractNote={An occipitoatlantoaxial malformation and ventricular septal defect (VSD) were diagnosed in a 36-hour-old female camel. Physical examination revealed a firm protrusion of the dorsal aspect of the atlas and axis, tilting of the head to the left, and a grade V/VI systolic murmur. Neurological examination revealed proprioceptive deficits and ataxia of all 4 limbs. Radiographic examination and necropsy demonstrated malformation, fusion of the atlas to the occiput and hypoplasia of the dens of the axis, and subluxation of the atlantoaxial joint. Dorsoventral laxity of the atlantoaxial joint was also present, with compression of the cervical spinal cord. A 1.5-cm-diameter VSD was observed also. Histopathologic examination of the cervical spinal cord revealed a cavity extending from the level of the first to fourth cervical segment, dorsal to the central canal, 5 cm long and 1-2 mm in diameter. The cells around the cavity were positive for glial fibrillary acidic protein and sporadically positive for vimentin. This cavitary structure was consistent with syringomyelia, which was lined by glial cells, surrounded by edematous white matter with Wallerian-like degeneration and with neuronal necrosis in the adjacent dorsal horns.}, number={4}, journal={Journal of Veterinary Diagnostic Investigation}, publisher={SAGE Publications}, author={Sakamoto, K and Kiupel, M and Frank, N and March, PA}, year={2004}, month={Jul}, pages={337–340} }
 @article{sakamoto_white_2002, title={Dermal Melanoma with Schwannoma-Like Differentiation in a Brown Bullhead Catfish (<i>Ictalurus Nebulosus</i>)}, volume={14}, DOI={10.1177/104063870201400311}, abstractNote={A dermal melanoma with histologic similarities to mammalian melanocytic schwannomas was diagnosed in a wild-caught brown bullhead catfish (Ictalurus nebulosus). The diagnosis was based on cytologic, histopathologic, immunohistochemical, and ultrastructural findings. The neoplasm protruded from the cutaneous surface of the dorsal midline immediately caudal to the dorsal fin, was diffusely black and focally ulcerated, and was attached to the underlying skin by a broad-based stalk. Cytologically, the tumor was composed of a monomorphic population of melanophores, the melanin-producing and storing cells within the dermis and epidermis of fish that are partially responsible for rapid color changes. Histopathologic examination of the neoplasm revealed an unencapsulated, well-circumscribed, moderately cellular neoplasm composed of 2 distinct cell populations: spindle cells arranged in a "herringbone" pattern and numerous melanophores. The spindle cells had scant bipolar eosinophilic cytoplasm, with small centrally located vesicular nuclei; nucleoli were not seen. The histologic appearance was similar to that described for mammalian melanocytic schwannomas. Immunohistochemically, the spindle cells exhibited positive cytoplasmic staining for S-100 protein but were negative for vimentin, neurofilament protein, and glial fibrillary acidic protein. Ultrastructurally, the tumor consisted of neoplastic spindle cells with rudimentary cell junctions, actin bundles, and few melanosomes and melanophores with abundant intracytoplasmic melanosomes.}, number={3}, journal={Journal of Veterinary Diagnostic Investigation}, publisher={SAGE Publications}, author={Sakamoto, K and White, MR}, year={2002}, month={May}, pages={247–250} }
 @article{hurty_brazik_law_sakamoto_lewbart_2002, title={Evaluation of the tissue reactions in the skin and body wall of koi (Cyprinus carpio) to five suture materials}, volume={151}, ISSN={["0042-4900"]}, DOI={10.1136/vr.151.11.324}, abstractNote={Five different suture materials (silk, monofilament nylon, polyglyconate, polyglactin 910, and chromic gut) were placed in the skin and body wall of 10 Doitsu (scaleless) koi (Cyprinus carpio). After seven days the sutures were retrieved from five of the fish in 5 mm and 6 mm punch biopsies, and after 14 days they were retrieved in the same way from the other five. The tissue reactions were evaluated by gross visual inspection and by histological examination. The total inflammatory reaction was graded on a scale from 0 (no inflammation) to 5 (severe inflammation). The synthetic suture materials generally induced a moderate inflammatory reaction that decreased after seven days. After 14 days the superficial reaction to monofilament nylon was substantial, and the tissue reactions to the organic suture materials were slightly greater than the reactions to the synthetics. The inflammatory response to silk was greater after 14 days than after seven, and chromic gut induced a moderately severe inflammatory response after seven days; the chromic gut sutures fell out before the biopsies were taken after 14 days. The organic materials induced intense inflammatory reactions which did not subside if the suture remained in the tissue.}, number={11}, journal={VETERINARY RECORD}, publisher={Wiley}, author={Hurty, CA and Brazik, DC and Law, JM and Sakamoto, K and Lewbart, GA}, year={2002}, month={Sep}, pages={324-+} }
 @article{wang_sakamoto_khosla_sannes_2002, title={Pre- and postnatal lung development, maturation, and plasticity: Detection of chondroitin sulfates and decorin in developing fetal and neonatal rat lung}, volume={282}, ISSN={["1522-1504"]}, DOI={10.1152/ajplung.00160.2001}, abstractNote={Chondroitin sulfates and their related proteoglycans are components of extracellular matrix that act as key determinants of growth and differentiation characteristics of developing lungs. Changes in their immunohistochemical distribution during progressive organ maturation were examined with monospecific antibodies to chondroitin sulfate, a nonbasement membrane chondroitin sulfate proteoglycan, and the specific chondroitin sulfate-containing proteoglycan decorin in whole fetuses and lungs from newborn and adult rats. Alveolar and airway extracellular matrix immunostained heavily in the prenatal rat for both chondroitin sulfate and chondroitin sulfate proteoglycan, whereas decorin was confined to developing airways and vessels. These sites retained their respective levels of reactivity with all antibodies through 1–10 days postnatal but thereafter became progressively more diminished and focal in alveolar regions. The heavy staining seen early in development was interpreted to reflect a significant and wide distribution of chondroitin sulfates, chondroitin sulfate proteoglycans, and decorin in rapidly growing tissues, whereas the reduced and more focal reactivity observed at later time points coincided with known focal patterns of localization of fibrillar elements of the extracellular matrix and a more differentiated state.}, number={3}, journal={AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY}, publisher={American Physiological Society}, author={Wang, YQ and Sakamoto, K and Khosla, J and Sannes, PL}, year={2002}, month={Mar}, pages={L484–L490} }
 @article{sakamoto_lewbart_smith_2001, title={Blood chemistry values of juvenile red pacu (Piaractus brachypolmus)}, volume={30}, ISSN={["0275-6382"]}, DOI={10.1111/j.1939-165x.2001.tb00257.x}, abstractNote={Abstract:Blood samples were collected from 29 juvenile red pacu (Piaractus brachypomus), ornamental freshwater fish, to establish baseline blood chemistry values. Mean (minimum‐maximum) values, obtained by automated bichromatic analysis and ion selective electrode analysis, were as follows: sodium, 150.4 (146–159) mmol/L; potassium, 3.93 (2.7–5.0) mmol/L; chloride, 138.7 (128–150) mmol/L; total CO2, 7.5 (6–10) mmol/L; albumin, 0.86 (0.5–1.0) g/dL; lactate dehydrogenase, 237.8 (65–692) IU/L; aspartate aminotransferase, 49.1 (0–125) IU/L; creatinine, 0.31 (0.2–0.4) mg/dL; calcium, 10.80 (9.5–12.5) mg/dL; anion gap, 6.89 (1.2–12.5) mmol/L; and phosphorus, 7.29 (4.1–8.9) mg/dL.}, number={2}, journal={VETERINARY CLINICAL PATHOLOGY}, publisher={Wiley}, author={Sakamoto, K and Lewbart, GA and Smith, TM}, year={2001}, pages={50–52} }
 @misc{sakamoto_janovitz_2001, title={Primitive Neuroectodermal Tumor in a Donkey}, author={Sakamoto, K and Janovitz, EB}, year={2001}, month={Aug} }
 @misc{sakamoto_white_2000, title={Leiomyomas and Seminomas in Yellow Perch}, author={Sakamoto, K and White, MR}, year={2000}, month={Aug} }
 @article{sannes_sakamoto_wang_1997, title={Immunohistochemical distribution of chondroitin sulfate and chondroitin sulfate proteoglycan in developing and adult rat lung}, volume={155}, journal={American Journal of Respiratory Critical Care Medicine}, author={Sannes, P.L. and Sakamoto, K. and Wang, J.}, year={1997}, pages={A181} }
 @article{freedman_sakamoto_scheele_1994, title={Nonparallel secretion of GP-2 from exocrine pancreas implies luminal coupling between acinar and duct cells}, volume={267}, ISSN={0193-1857 1522-1547}, url={http://dx.doi.org/10.1152/ajpgi.1994.267.1.g40}, DOI={10.1152/ajpgi.1994.267.1.g40}, abstractNote={The in vivo and in vitro secretion of glycoprotein-2 (GP-2), a glycosyl phosphatidylinositol (GPI)-anchored protein from the rat exocrine pancreas, was characterized. GP-2 was secreted in a nonparallel manner compared with amylase, a marker of secretory enzymes. Attenuated GP-2 secretion correlated with hormones that stimulated exocytosis in acinar cells. Augmented GP-2 secretion correlated with hormones that stimulated fluid and bicarbonate secretion from ductal elements. Immunofluorescence studies identified an enriched pool of GP-2 tightly bound to the apical membranes of acinar cells in addition to zymogen granules. This non-zymogen granule pool appears to represent the source of GP-2 released from acinar cells in a nonparallel manner. With the use of dispersed pancreatic acini largely devoid of ductal elements, GP-2 release was found to be augmented by alkaline pH. Thus GP-2 secretion appears to be modulated by two discrete cellular processes: 1) delivery of prereleased GP-2 within zymogen granules to the ductal lumen by exocytic mechanisms and 2) enzymatic release of GPI-anchored GP-2 from the luminal membranes, a kinetic process that appears to be regulated by secretin- or carbachol-induced secretion of bicarbonate.}, number={1}, journal={American Journal of Physiology-Gastrointestinal and Liver Physiology}, publisher={American Physiological Society}, author={Freedman, S. D. and Sakamoto, K. and Scheele, G. A.}, year={1994}, month={Jul}, pages={G40–G51} }
 @article{freedman_sakamoto_venu_1993, title={GP2, the homologue to the renal cast protein uromodulin, is a major component of intraductal plugs in chronic pancreatitis.}, volume={92}, DOI={10.1172/jci116602}, abstractNote={Protein plug obstruction of the pancreatic duct is one of the early events in chronic pancreatitis yet little is known about its pathogenesis. GP2, a protein in the exocrine pancreas, is a glycosyl phosphatidylinositol-anchored protein that is cleaved from the zymogen granule membrane and secreted into pancreatic juice. Since its homologue, uromodulin, is involved in renal cast formation, we asked the question whether GP2 might play a similar role in plug formation in chronic pancreatitis. The protein composition of intraductal plugs from patients with noncalcific chronic pancreatitis was examined. Plugs purified from pancreatic juice obtained by endoscopic cannulation were analyzed by SDS-PAGE. A 97-kD protein was found not only to be a reproducible constituent but also enriched within intraductal plugs. This protein was confirmed as GP2 by its localization to zymogen granule membranes, its isoelectric point, and by Western blotting. Although the pancreatic stone protein was identified in plugs, it was not a major reproducible component. These results demonstrate that GP2 is an integral component of plugs in pancreatic juice and suggest that GP2 may play a role in pancreatic plug formation that is analogous to the role played by uromodulin in the pathogenesis of renal casts.}, number={1}, journal={Journal of Clinical Investigation}, publisher={American Society for Clinical Investigation}, author={Freedman, SD and Sakamoto, K and Venu, RP}, year={1993}, month={Jul}, pages={83–90} }
 @inproceedings{alagappan_budischak_megow_bringuel_sellers_patel_kamau-nataki_zehner_urban_ezenwa_et al., title={A Mouse Model of Dual Helminth and Mycobacterium bovis Co-infection}, author={Alagappan, J and Budischak, S and Megow, L and Bringuel, B and Sellers, L and Patel, N and Kamau-Nataki, O and Zehner, A and Urban, J and Ezenwa, V and et al.} }
 @inproceedings{cazzini_sakamoto_zimmerman_garner, title={An Abdominal Mass in a Young Dog}, author={Cazzini, P and Sakamoto, K and Zimmerman, S and Garner, B} }
 @phdthesis{zimmerman, title={Animal Model and Vaccine Candidate Development for Burkholderia mallei and Burkholderia pseudomallei}, author={Zimmerman, S} }
 @inproceedings{sakamoto_budischak_ezenwa, title={Causes and Consequences of Parasite Community Composition}, author={Sakamoto, K and Budischak, S and Ezenwa, V} }
 @inproceedings{sakamoto_bowdish_mukhopadhyay_kim_leifer_tryggvason_gordon_russell, title={Class A Scavenger Receptors are Important in the Recognition and Response to Mycobacterium tuberculosis and Mycobacterial Trehalose Dimycolate}, author={Sakamoto, K and Bowdish, DME and Mukhopadhyay, S and Kim, M and Leifer, CA and Tryggvason, K and Gordon, S and Russell, DG} }
 @inproceedings{gupta_chen_lagatta_sakamoto_karls_quinn_he, title={Developing a parainfluenza virus 5 (PIV5)-based Mycobacterium tuberculosis vaccine}, author={Gupta, T and Chen, Z and Lagatta, M and Sakamoto, K and Karls, R and Quinn, F and He, B} }
 @phdthesis{budischak, title={Disturbance reveals the role of biotic interactions in parasite community assembly}, author={Budischak, S} }
 @inproceedings{sakamoto_geisel_rhoades_rohde_russell, title={Effect of Mode of Presentation on Macrophage Response to Trehalose Dimycolate}, author={Sakamoto, K and Geisel, RE and Rhoades, ER and Rohde, KH and Russell, DG} }
 @phdthesis{frontera-acevedo, title={Feline Immune Response to Infection with Cytauxzoon felis and the Role of CD18 in the Pathogenesis of Cytauxzoonosis}, author={Frontera-Acevedo, K} }
 @inproceedings{sakamoto_kelly_kasperbauer_camus_mayer_divers_cazzini, title={Feline Infectious Peritonitis-like Syndrome in a Ferret}, author={Sakamoto, K and Kelly, D and Kasperbauer, K and Camus, M and Mayer, J and Divers, S and Cazzini, P} }
 @inproceedings{sakamoto_rhoades_russell, title={Inhibitory Effects of Mycobacterium bovis BCG-infected Macrophage Conditioned Medium on Lymphocyte Activation}, author={Sakamoto, K and Rhoades, ER and Russell, DG} }
 @phdthesis{cazzini, title={Intestinal Lymphoma and Inflammatory Bowel Disease in Ferrets (Mustela putorius furo)}, author={Cazzini, P} }
 @inproceedings{frontera-acevedo_sakamoto, title={Local Pulmonary Immune Responses in Cytauxzoon felis-infected Domestic Cats}, author={Frontera-Acevedo, K and Sakamoto, K} }
 @inproceedings{sakamoto_russell_rohde, title={Macrophage Gene Regulation and Matrix Metalloproteinase Activation by Mycobacterial Trehalose Dimycolate}, author={Sakamoto, K and Russell, DG and Rohde, KH} }
 @inproceedings{sakamoto_white, title={Melanocytic Schwannoma in a Brown Bullhead Catfish (Ictalurus nebulosus)}, author={Sakamoto, K and White, MR} }
 @inproceedings{budischak_megow_zehner_bringuel_sellers_cumming_moorhead_urban_ezenwa_sakamoto, title={Murine Intestinal Nematode Co-infection: Effects on the Parasites and the Host}, author={Budischak, S and Megow, L and Zehner, A and Bringuel, B and Sellers, L and Cumming, KR and Moorhead, AR and Urban, J and Ezenwa, V and Sakamoto, K} }
 @phdthesis{pandarangga, title={PATHOGENESIS OF NEW SUB-GENOTYPE OF NEWCASTLE DISEASES  VIRUS STRAINS FROM ISRAEL AND PAKISTAN}, author={Pandarangga, P} }
 @inproceedings{edwards_williamson_garner_storey_sakamoto, title={Pathology of Haemonchus contortus in New World Camelids in Georgia: A Retrospective Study}, author={Edwards, E and Williamson, LH and Garner, B and Storey, B and Sakamoto, K} }
 @inproceedings{frontera-acevedo_dugan_sellers_sakamoto, title={Proinflammatory Cytokines and CD18 Expression in C. felis-infected Cats}, author={Frontera-Acevedo, K and Dugan, M and Sellers, L and Sakamoto, K} }
 @phdthesis{susta, title={ROLE OF INDIVIDUAL GENES, GENOTYPES AND CYTOKINES IN THE PATHOGENESIS AND VIRULENCE OF NEWCASTLE DISEASE}, author={Susta, L} }
 @inproceedings{coulson_bowdish_sakamoto, title={Role of MARCO Scavenger Receptor in Resistance to Tuberculosis}, author={Coulson, G and Bowdish, DME and Sakamoto, K} }
 @inproceedings{sakamoto_dugan_balsone_sellers_brown_peterson_makemson_frontera-acevedo, title={Systemic Immunopathogenesis of Cytauxzoonosis}, author={Sakamoto, K and Dugan, M and Balsone, N and Sellers, L and Brown, HM and Peterson, DS and Makemson, M and Frontera-Acevedo, K} }
 @phdthesis{huang, title={THE IMPORTANCE OF VIRUS NEUTRALIZATION ANTIBODIES AND BLOOD-BRAIN-BARRIER PERMEABILITY EHANCEMENT IN CLEARING RABIES VIRUS FROM THE CENTRAL NERVOUS SYSTEM}, author={Huang, C} }
 @inproceedings{sakamoto_vannberg_lack_hill_gordon_rodgers_sellers_bowdish, title={The Macrophage Scavenger Receptor MARCO Contributes to Host Defense Against Tuberculosis}, author={Sakamoto, K and Vannberg, FO and Lack, NA and Hill, AVS and Gordon, S and Rodgers, A and Sellers, L and Bowdish, DME} }
 @article{tmx  induces histological changes }