@article{suyemoto_spears_hamrick_barnes_havell_orndorff_2010, title={Factors Associated with the Acquisition and Severity of Gestational Listeriosis}, volume={5}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0013000}, abstractNote={Gravid mammals are more prone to listeriosis than their nongravid counterparts. However, many features of the disease in gravid animals are not well defined. We determined, in mice, that increased susceptibility to lethal infection following oral inoculation begins surprisingly early in pregnancy and extends through embryonic development. Pregnancy did not demonstrably increase the spread of listeriae from the intestine to the liver and spleen in the initial 96 h period post inoculation. Consequently, it appeared that gravid animals were competent to contain an enteric infection, but in those instances where escape did occur, a lethal outcome was more likely. Interestingly, colonic colonization level and prevalence, measured 96 h post inoculation, was significantly higher in gravid individuals. In terms of human risk factors for listeriosis, our results suggest that the window of listeriosis susceptibility afforded by pregnancy may be open longer than previously appreciated. Our results also suggest that while gravid animals are competent to contain an enteric infection, enteric carriage rate may be more of a factor in defining disease incidence than previously considered.}, number={9}, journal={PLOS ONE}, author={Suyemoto, M. Mitsu and Spears, Patricia A. and Hamrick, Terri S. and Barnes, Jill A. and Havell, Edward A. and Orndorff, Paul E.}, year={2010}, month={Sep} }
 @article{cora_neel_tarigo_post_barnes_2010, title={Francisella philomiragia Septicemia in a Dog}, volume={24}, ISSN={["0891-6640"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-77956640280&partnerID=MN8TOARS}, DOI={10.1111/j.1939-1676.2010.0545.x}, abstractNote={A 10-month-old, male castrated bulldog weighing 18.4 kg was presented to the North Carolina State University Veterinary Teaching Hospital (NCSU-VTH) for evaluation of severe neck pain and lethargy. Two months previously, the dog had presented to the referring veterinarian with signs of lethargy and severe neck pain, and the owners reported recent removal of ticks from the dog at that time. A CBC, a biochemistry panel, and spinal radiographs were unremarkable, and an in-house canine ELISAa test for heartworm disease, Anaplasma phagocytophilum, Ehrlichia canis, and Borrelia burgdorferi was negative. The patient was treated with meloxicamb (0.1 mg/kg PO q24h) and a 3-week course of doxycycline (5.9 mg/kg PO q12h), after which improvement was noted. However, similar clinical signs returned approximately 7 weeks after the initial episode. Doxycycline (5.5 mg/kg PO q12h) was restarted and clindamycin (16.6 mg/kg PO q12h) added for possible toxoplasmosis. There was no improvement 3 days after initiation of treatment, and referral to NCSU-VTH was recommended. On physical examination, the patient was febrile (103.5°F), with dull mentation, low head carriage, stiff neck, and trembling in all limbs. Profound vocalization was elicited on flexion, extension, and lateralization of the neck consistent with severe pain. Neurologic reflexes were normal. A serum biochemistry profile showed mild hyperglycemia (129 mg/dL; reference interval, 60–110 mg/dL). A CBC performed on a point-of-care analyzer disclosed mild normocytic, normochromic anemia (Hct, 36.2%; reference interval, 37–55%) and mild leukocytosis (21.8 × 103/μL; reference interval, 6.0–17.0 × 103/μL) characterized by mature neutrophila (18.09 × 103/μL; reference interval, 2.8–9.1 × 103/μL) and monocytosis (1.5 × 103/μL; reference interval, 0.59–0.85 × 103/μL). Differential diagnosis for the leukogram included inflammation or a physiological response. Urinalysis and thoracic radiographs were unremarkable. Evaluation of cisternal CSF indicated extreme neutrophilic (nondegenerate) pleocytosis with severely increased protein concentration (TNCC, 3,000/μL; protein, 175 mg/dL) consistent with meningitis. Pooled blood and CSF samples were polymerase chain reaction (PCR) negative for A. phagocytophilum, E. canis, B. burgdorferi, Toxoplasma gondii, Neospora spp., canine distemper virus, and West Nile virus.c A CSF culture was not performed. Before the results of the aforementioned infectious disease tests were available, treatment with doxycycline and clindamycin was continued, and prednisone (1.1 mg/kg q12h) was started. Five days later when the results were available, antibiotics were discontinued and a presumptive diagnosis of steroid responsive meningitis-arteritis (SRMA) was made. The patient's clinical signs resolved. Approximately 7 weeks later, while still receiving prednisone (0.27 mg/kg q12h), the dog became lethargic and inappetent with slight head tremors. Examination by the referring veterinarian identified a fever of 105°F and the patient was hospitalized at the referring veterinarian's hospital. Concerned over a potential relapse of the presumptive SRMA, the referring veterinarian consulted the attending neurologist at NCSU-VTH by phone. Although relapse of the SRMA was considered, the possibility of infection secondary to immunosuppression also was discussed and additional diagnostics, including reevaluating the CSF, was recommended. Empirically, under the referring veterinarian's care, the antibiotics were restarted and the prednisone dosage ultimately increased (1.6 mg/kg q12h). The dog showed no improvement during hospitalization for 4 days and was transferred to NCSU-VTH. At 2nd presentation to NCSU-VTH, the patient was stuporous and febrile (103°F). Occasional head tremors were noted, and spinal reflexes were delayed. The mucous membranes were pale with multifocal petechiae. Melena was observed. A serum biochemistry profile showed mild hypoalbuminemia (2.2 g/dL; reference interval, 2.5–4.4 g/dL), mild hyperbilirubinemia (0.8 mg/dL; reference interval, 0.1–0.6 mg/dL), and increased ALP (1195 IU/L; reference interval, 20–150 IU/L) and ALT (318 IU/L; reference interval, 10–118 IU/L). A CBC indicated moderate, normocytic, normochromic, nonregenerative anemia (Hct, 21.3%; reference interval, 39.2–55.9%), severe thrombocytopenia (13 × 103/μL; reference interval, 190–468 × 103/μL), and mild leukopenia (4.02 × 103/μL; reference interval, 4.39–11.61 × 103/μL) characterized by neutropenia (1.9 × 103/μL; reference interval, 2.8–9.1 × 103/μL) with a left shift (0.32 × 103/μL). A coagulation panel showed both prolonged PT (11.8 s; reference interval, 6.8–10.7 s) and APTT (46.4 s; reference interval, 75–13.8 s) with D-dimers > 2,000 ng/dL (reference interval, < 250 ng/dL) and a fibrinogen concentration of 100 mg/dL (reference interval, 100–300 mg/dL). Thoracic radiographs were unremarkable. Blood smear examination identified low numbers of spherocytes and marked neutrophilic toxic change. Moderate numbers of monocytes and neutrophils had mild to moderate nuclear swelling or karyorrhexis consistent with degenerative changes, and virtually every neutrophil and monocyte contained varying numbers of small (0.2–1 μm), pale basophilic, irregularly round, oblong, linear, or curvilinear structures consistent with a pleomorphic bacterial population (Fig 1). Initially, because of the pleomorphic morphology of the bacteria paired with their presence within both monocytes and neutrophils, Rhodococcus equi was considered a potential cause of the septicemia. However, a Gram stain indicated a gram-negative organism. CBC and blood smear findings were consistent with severe overwhelming inflammation becuase of septicemia. The anemia most likely was caused by a combination of blood loss, anemia of inflammatory disease and immune-mediated hemolytic anemia, potentially secondary to treatment or the bacterial infection. The coagulation panel supported fulminant disseminated intravascular coagulation (DIC). Peripheral blood smear, Wright-Giemsa staining (100x objective). Ruptured leukocytes with released F. philomiragia bacteria in the background. Note the pleomorphism among the bacteria. 650 × 520 mm (150 × 150 DPI). Despite treatments, including IV fluid therapy, ampicillin/sulbactam (22 mg/kg IV q8h), famotidine (0.5 mg/kg IV q12h), pantoprazole (1 mg/kg IV q24h), fresh frozen plasma, and packed RBC transfusions, the patient continued to deteriorate, became nonresponsive, and was euthanized 19 hours after admission. At necropsy, macroscopic examination disclosed moderate disseminated petechiae in the subcutis, mucous membranes, diaphragm, mesentery, kidney, lungs, heart, and serosal surfaces of the gastrointestinal tract consistent with the clinical and laboratory diagnosis of fulminant DIC. CSF was collected for culture. Histopathology of liver, spleen, bone marrow, lungs, and various lymph nodes identified multifocal to disseminated, moderate to severe, histiocytic inflammation with large numbers of intrahistiocytic, Gram-negative bacterial organisms with accompanying necrosis, hemorrhage, and fibrin deposition. Within the brain, mild, multifocal lymphoplasmacytic meningoencephalitis and choroiditis were observed, but no areas of histiocytic inflammation or bacterial organisms were found. Whole blood and CSF were submitted for bacterial culture. Whole blood and the bacterial isolate from the blood culture were frozen and stored at −70°C. Culture of the CSF yielded a weakly fermenting, Gram negative rod that could not be further characterized, and the isolate was sent to the state diagnostic laboratory.d Based on conventional macrotube biochemical methods and phenotypic properties, further characterization was again not possible, and the isolate was sent to a reference laboratorye for molecular identification. PCR amplification of 16S rRNA gene segments yielded sequences consistent with Francisella philomiragia (>99% identity). To confirm F. philomiragia as the cause of the septicemia, PCR amplification of 16S rRNA gene segments was performedf as previously described1 on the saved whole blood, banked blood smear, and blood culture isolate and yielded sequences consistent with F. philomiragia (>99% identity). To the authors' knowledge, this is the first reported case of F. philomiragia septicemia in a dog. Francisella species are small, facultatively intracellular, Gram negative, catalase positive, pleomorphic coccobacilli. There are 2 recognized species, F. tularensis (agent of tularemia or “rabbit fever”) and F. philomiragia. Several subspecies of F. tularensis exist. Although Francisella species are morphologically similar and share similar biochemical activities and a high degree of DNA relatedness, F. tularensis and F. philomiragia contrast markedly in their epidemiological and clinical features.2, 3F. tularensis is more virulent, and most infections occur in immunocompetent individuals. In the United States, tularemia is acquired primarily by contact with infected ticks or animals (especially rabbits) or ingestion of contaminated meat or freshwater. In contrast, F. philomiragia is an opportunistic agent that rarely is reported to cause clinical disease. Isolation of this species is infrequent with only 18 isolations over a 40-year period (1 animal and 17 human) reported in the literature.4-7 Most isolates are from North America with one each from Turkey and Switzerland. The majority are associated with salt water exposure with neither animal nor arthropod vectors implicated in human transmission. F. philomiragia was first isolated in 1969 in Utah from a dying muskrat and the water in the surrounding marshy area where it was found (part of the Great Salt Lake waterway).6 Originally classified as Yersinia philomiragia, it was reclassified as F. philomiragia in 1989 based on biochemical and genetic tests.3F. philomiragia is only rarely reported in the literature as a cause of invasive infection (pneumonia, sepsis, meningitis) in humans. In 1 case series of 14 patients infected with F. philomiragia, 3 groups were reported at risk: patients with either chronic granulomatous disease (CGD) or myeloproliferative disease, and those surviving a near-drowning in salt or estuary water.4 It was also found that 12 of the 14 patients lived within 50 miles of a salt water coastline.4 These diseases and situations render individuals more susceptible to infection because of an impaired physical barrier to infection (near-drowning) or an impaired immune system (CGD, myeloproliferative disease).2, 4 CGD is a group of inherited disorders characterized by the inability of phagocytes to produce reactive oxygen species, including hydrogen peroxide, owing to a defect in the NADPH oxidase system. Affected individuals develop recurrent infections and granulomatous lesions caused by a narrow range of bacteria and fungi.8 Catalase negative organisms (ie, streptococci) can be killed because of the accumulation of their own endogenous hydrogen peroxide within phagocytic vacuoles.5 In contrast, catalase-positive organisms including F. philomiragia and others (Staphylococcus aureus, Serratia spp., Aspergillus spp.) metabolize their endogenous hydrogen peroxide, leaving affected individuals vulnerable to infection.4, 5 Humans with CGD and subsequent F. philomiragia infection had fever, pneumonia, sepsis, meningitis, or a combination of these, with the bacterium isolated from blood, lung biopsy samples, or CSF.4, 5, 7 One patient died of septicemia. Patients receiving chemotherapy for treatment of a myeloproliferative disorder presented with fever and had F. philomiragia isolated from pericardial fluid and blood.4 Lung damage secondary to near drowning renders immunocompetent individuals susceptible to invasive infection by normally nonpathogenic organisms. All of the near drowning-associated human infections occurred in association with salt or estuary water.4 These patients were diagnosed with either pneumonia or sepsis with the bacterium isolated from blood in all cases. As with human cases of F. philomiragia infection, conventional identification of the bacterial isolate was challenging. Microscopically, culture isolates may be highly pleomorphic with bizarre, irregular to coccobacillary forms.5, 7 They are relatively fastidious with slow growth and give weak or delayed reactions in conventional biochemical test methods (eg, acid production from glucose, maltose, and sucrose).3, 5, 7 In this case, these characteristics necessitated identification by PCR amplification of 16S rRNA gene segments, ultimately confirming infection with F. philomiragia. Although 16S rRNA gene sequencing yields the most rapid identification of F. philomiragia, identification by biochemical characteristics is possible. Recognition of a highly pleomorphic, fastidious, halophilic bacterium combined with the production of oxidase (usually weak positive) and gelatinase is highly suggestive.3, 5, 7 Although antimicrobial susceptibility testing of Francisella species is not standardized, successful treatment of F. philomiragia based on broth microdilution method was achieved in the majority of reported human cases.4F. philomiragia isolates were susceptible in vitro to aminoglycosides, cefoxitin, cefotaxime, tetracycline, and chloramphenicol. They were resistant to ampicillin and produced β-lactamase. Successful treatment with ciprofloxacin recently has been reported.5 Despite its in vitro susceptibility to tetracycline and chloramphenicol, treatment alone with a bacteriostatic antibiotic may result in treatment failures because F. philomiragia is a facultatively intracellular bacterium. It is unclear whether or not this patient's clinical disease at the time of initial presentation was because of SRMA. There is no definitive antemortem test for SRMA and diagnosis is based on a combination of clinical signs, nonspecific laboratory findings and exclusion of other diseases. The dog may have already been infected with F. philomiragia, and infection rendered subclinical by initial treatment with doxycycline. Although the dog did not seem to have any of the 3 major risk factors identified in humans, like the majority of human F. philomiragia infections, this patient lived within 50 miles of a salt water coast (coastal town of North Carolina) and the owners reported taking the dog to swim in the river the week before the first visit to NCSU-VTH. Alternatively, immunosuppressive doses of prednisone may have predisposed the dog to bacterial infection, resulting in infection during the course of treatment for presumptive SRMA. F. philomiragia is an opportunistic bacterium that should be considered as a cause of invasive infection in immune-compromised veterinary patients or in those with compromised lung tissue (ie, near drowning event, aspiration pneumonia), especially if the patient has contact with, or lives near, salt water. Similar to R. equi, the unique, pleomorphic, coccobacillary appearance of the organism and its location within monocytes, macrophages, and neutrophils is helpful in identification. Familiarity with this organism is important for appropriate antibiotic administration and successful treatment. aCanine SNAP 4Dx, IDEXX Laboratories Inc, Westbrook, ME bMetacam, Boehringer Ingelheim Vetmedica Inc, St. Joesph, MO cLucy Whitter Molecular and Diagnostics Core Facility—TaqMan Service, Davis, CA dNorth Carolina Veterinary Diagnostic Laboratory System-Rollins, Raleigh, NC eWashington Animal Disease Diagnostic Lab, Pullman, WA fVector Borne Diagnostic Disease Laboratory, North Carolina State University, Raleigh, NC}, number={4}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Cora, M. C. and Neel, J. A. and Tarigo, J. and Post, K. and Barnes, J.}, year={2010}, pages={969–972} }
 @article{ghatnekar_barnes_dow_smoak_2004, title={Hypoglycemia-induced changes in cell death and cell proliferation in the organogenesis-stage embryonic mouse heart (Retracted article. See vol 76, pg 278, 2006)}, volume={70}, ISSN={["1542-0760"]}, DOI={10.1002/bdra.20000}, abstractNote={Abstract}, number={3}, journal={BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY}, author={Ghatnekar, GS and Barnes, JA and Dow, JL and Smoak, IW}, year={2004}, month={Mar}, pages={121–131} }
 @article{gazdzinski_barnes_2004, title={Venereal colibacillosis (acute vaginitis) in turkey breeder hens}, volume={48}, ISSN={["0005-2086"]}, DOI={10.1637/7163-020204R}, abstractNote={Abstract Two flocks of turkey breeders experienced an increased mortality and high culling rate in the first weeks of egg production. The majority of dead and culled hens had cheesy core in the cloaca and vagina. Postmortem examination revealed fibrinous pseudomembranes in the vagina and cloaca. The thickness of these membranes posed an obstruction to egg passage leading to internal laying and egg peritonitis. Swabs from cloaca and vagina produced numerous colonies of only E. coli. Investigations of this unusual vaginitis showed that these two flocks had a higher number of immature hens with present hymens, and insemination crews mistakenly inseminated all hens in which they were able to evert the cloaca. Breaking the hymen with an insemination pipette created a wound and developed extensive infection with E. coli bacteria.}, number={3}, journal={AVIAN DISEASES}, author={Gazdzinski, P and Barnes, J}, year={2004}, month={Sep}, pages={681–685} }
 @article{barnes_collins_dix_allen_2002, title={Effects of heat shock protein 70 (Hsp70) on arsenite-induced genotoxicity}, volume={40}, ISSN={["0893-6692"]}, DOI={10.1002/em.10116}, abstractNote={Abstract}, number={4}, journal={ENVIRONMENTAL AND MOLECULAR MUTAGENESIS}, author={Barnes, JA and Collins, BW and Dix, DJ and Allen, JW}, year={2002}, pages={236–242} }
 @article{barnes_smoak_2000, title={Glucose-regulated protein 78 (GRP78) is elevated in embryonic mouse heart and induced following hypoglycemic stress}, volume={202}, ISSN={["0340-2061"]}, DOI={10.1007/s004290000090}, abstractNote={This study investigates the distribution and heart levels of glucose regulated protein (GRP) 78 during normal development and in response to hypoglycemia in the mouse. Results demonstrate that GRP78 is strongly expressed with in the heart, neural tube, gut endoderm, somites, and surface ectoderm of mouse embryos during early organogenesis, and GRP78 staining remains prominent in the heart from gestational days 9.5 through 13.5. Cardiac myocytes are the primary site of GRP78 expression within the heart. GRP78 levels are highest in the heart during early organogenesis and levels decrease significantly by the fetal period. GRP78 expression is increased after 24 h of hypoglycemia in the early organogenesis-stage heart. Considering the tissue specific pattern of GRP expression and changes during development of the heart, GRPs may play significant roles in the normal differentiation and development of cardiac tissue. GRP induction may also be involved in hypoglycemia-induced cardiac dysmorphogenesis.}, number={1}, journal={ANATOMY AND EMBRYOLOGY}, author={Barnes, JA and Smoak, IW}, year={2000}, month={Jul}, pages={67–74} }
 @article{barnes_smoak_branch_1999, title={Expression of glucose-regulated proteins (GRP78 and GRP94) in hearts and fore-limb buds of mouse embryos exposed to hypoglycemia in vitro}, volume={4}, ISSN={["1355-8145"]}, DOI={10.1379/1466-1268(1999)004<0250:EOGRPG>2.3.CO;2}, abstractNote={Hypoglycemia, the classic inducer of glucose-related protein (GRP) synthesis, is dysmorphogenic in rodent embryos and detrimentally affects the heart. This study compares GRP induction in a target vs non-target tissue by evaluating GRP expression in hearts and fore-limb buds of mouse embryos following exposure to hypoglycemia in vitro. Gestational day 9.5 embryos were exposed to 2, 6, and 24 h of either mild (80 mg/dl glucose) or severe (40 mg/dl glucose) hypoglycemia using the method of whole-embryo culture. GRP78 increased in a dose- and time-dependent fashion in embryonic hearts exposed to either 40 mg/dl or 80 mg/dl glucose, whereas GRP94 levels increased in hearts only after 24 h of hypoglycemia. In contrast to the heart, GRP induction in fore-limb buds occurred only with GRP78 following the most severe level and duration of hypoglycemia. RT-PCR analysis demonstrated an elevation in GRP78 and GRP94 message levels in embryonic hearts following severe hypoglycemia. However, mRNA levels did not increase in response to mild hypoglycemia. Overall, these data demonstrate the preferential induction of GRPs in the heart as compared to fore-limb buds in mouse embryos exposed to hypoglycemia. Increases in GRP protein levels may be a more reliable biomarker of stress than message levels. However, both tissues and methods should be examined for enhanced biomarker sensitivity.}, number={4}, journal={CELL STRESS & CHAPERONES}, author={Barnes, JA and Smoak, IW and Branch, S}, year={1999}, month={Dec}, pages={250–258} }