Abstract. The objective of this study was to determine whether vaccination with bacterins commonly used in the USA, when administered at a time typical of US protocol, enhances porcine circovirus type 2 (PCV2) replication and the incidence and severity of clinical signs and lesions characteristic of postweaning multisystemic wasting syndrome (PMWS) in conventional pigs. Sixty-one pigs free of PCV2 were randomly assigned to four groups. Groups 1 (n ϭ 15) and 2 (n ϭ 15) pigs served as sham-inoculated negative controls. Groups 3 (n ϭ 14) and 4 (n ϭ 17) pigs were inoculated intralymphoid with PCV2 field isolate ISU-40895. Pigs in groups 2 and 4 were vaccinated with Actinobacillus pleuropneumoniae (APP) and Mycoplasma hyopneumoniae (M. hyopneumoniae) bacterins 21 days before and again 1 day before inoculation with PCV2. Mild transient respiratory disease and diarrhea were observed from 13 to 34 days postinoculation (DPI) in pigs in groups 3 and 4. Half the pigs from each group were necropsied at 22 and 34 DPI, respectively. Moderately enlarged, tancolored lymph nodes were observed in the majority of pigs in groups 3 and 4. There was a significantly (P Ͻ 0.05) longer length of viremia (2.14 Ϯ 0.26 versus 4.44 Ϯ 0.23 weeks), a higher copy number of the PCV2 genome in serum, a wider range of tissue distribution of PCV2 antigen, and an increased severity of lymphoid depletion in pigs vaccinated with commercial APP and M. hyopneumoniae vaccines and inoculated with PCV2 compared with PCV2-inoculated unvaccinated pigs. Swine producers and veterinarians may need to consider changes in vaccination protocols in herds with recurrent PCV2-associated PMWS.
Shiga toxin (Stx)-producing Escherichia coli (STEC) causes hemorrhagic colitis and hemolytic-uremic syndrome (HUS).
Abstract.A 10-year-old terrier crossbreed presented with a change in bark intonation of 3-4 month's duration and pronounced panting. Four variably sized masses were observed within the oral cavity. The largest mass was located within the parenchyma at the caudal region of the tongue. Others were located on the left arytenoid, within the soft palate, and in the oropharynx above the soft palate. Histopathologic specimens consisted of large round to polygonal cells occasionally containing multiple nuclei and rare faint cytoplasmic cross striations. Staining was weakly positive with periodic acid-Schiff. Immunocytochemistry was strongly diffusely positive for muscle-specific actin, myoglobin, and desmin and scattered positive for S-100 and vimentin. Phosphotungstic acid-hematoxylin staining enhanced cytoplasmic cross striations. The cytoplasm of all neoplastic cells was filled with mitochondria on electron microscopy. The final diagnosis was multifocal/metastatic rhabdomyosarcoma.Key words: Dogs; multifocal rhabdomyosarcoma; nasopharynx; oral cavity; tongue.A 10-year-old crossbreed, spayed female terrier presented to Avondale Animal Hospital with a change in bark intonation of 3-4 month's duration and pronounced panting. Four variably sized masses were observed within the oral cavity. The largest mass was located within the muscle parenchyma at the caudal region of the tongue. Others were found on the left arytenoid, within the soft palate, and within the nasopharynx above the soft palate. Fine-needle aspirates from the tongue and arytenoid masses were submitted, stained with Wright's stain, and examined microscopically. The four specimens contained similar polygonal cells consisting of a round, vesicular nucleus with a prominent nucleolus often with anisonucleoliosis. The cytoplasm was abundant, containing numerous minute reddish granules. Moderate to marked anisocytosis and anisokaryosis were present. Multinucleated cells also were observed frequently. Granular cell tumor, oncocytoma, rhabdomyoma, or rhabdomyosarcoma were considered cytologically, with the granular cell tumor most likely due to location; however, because of the unusual multifocal or metastatic nature of the neoplasm, rhabdomyosarcoma also was considered.The dog was then referred to the Iowa State University veterinary teaching hospital. The dog appeared healthy without dyspnea. Hematologic and serum biochemical parameters were within the established reference values. On urinalysis, a 4ϩ proteinuria was present, with a urine protein-creatinine ratio of 4.21. Blood pressure was elevated at 208 mm Hg. Increased blood pressure and proteinuria findings were not associated with the oral masses.Surgical removal of the four masses was attempted. After debulking of the masses, laser treatment was performed to cauterize the surrounding regions that could not be removed. Tissue specimens were fixed in 10% buffered formalin for histopathology and also in glutaraldehyde for electron microscopy (EM). Formalin-fixed tissues were prepared and initially stained wi...
Immune clearance of Hepatitis B virus (HBV) is characterized by broad and robust antiviral T cell responses, while virus-specific T cells in chronic hepatitis B (CHB) are rare and exhibit immune exhaustion that includes programmed-death-1 (PD-1) expression on virus-specific T cells. Thus, an immunotherapy able to expand and activate virus-specific T cells may have therapeutic benefit for CHB patients. Like HBV-infected patients, woodchucks infected with woodchuck hepatitis virus (WHV) can have increased hepatic expression of PD-1-ligand-1 (PD-L1), increased PD-1 on CD8+ T cells, and a limited number of virus-specific T cells with substantial individual variation in these parameters. We used woodchucks infected with WHV to assess the safety and efficacy of anti-PD-L1 monoclonal antibody therapy (αPD-L1) in a variety of WHV infection states. Experimentally-infected animals lacked PD-1 or PD-L1 upregulation compared to uninfected controls, and accordingly, αPD-L1 treatment in lab-infected animals had limited antiviral effects. In contrast, animals with naturally acquired WHV infections displayed elevated PD-1 and PD-L1. In these same animals, combination therapy with αPD-L1 and entecavir (ETV) improved control of viremia and antigenemia compared to ETV treatment alone, but with efficacy restricted to a minority of animals. Pre-treatment WHV surface antigen (sAg) level was identified as a statistically significant predictor of treatment response, while PD-1 expression on peripheral CD8+ T cells, T cell production of interferon gamma (IFN-γ) upon in vitro antigen stimulation (WHV ELISPOT), and circulating levels of liver enzymes were not. To further assess the safety of this strategy, αPD-L1 was tested in acute WHV infection to model the risk of liver damage when the extent of hepatic infection and antiviral immune responses were expected to be the greatest. No significant increase in serum markers of hepatic injury was observed over those in infected, untreated control animals. These data support a positive benefit/risk assessment for blockade of the PD-1:PD-L1 pathway in CHB patients and may help to identify patient groups most likely to benefit from treatment. Furthermore, the efficacy of αPD-L1 in only a minority of animals, as observed here, suggests that additional agents may be needed to achieve a more robust and consistent response leading to full sAg loss and durable responses through anti-sAg antibody seroconversion.
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