Biology subjects

Howerth, E. W.

Publications and source records attributed to Howerth, E. W..

4 recordsLinked to original sources

bioRxiv2025

Frequency and Characterization of Rare Histologic Subtypes in Canine Invasive Urothelial Carcinoma

The histologic and molecular heterogeneity of human muscle-invasive bladder cancer (MIBC) is a major contributor to poor treatment outcomes. While most cases of MIBC are diagnosed as conventional urothelial carcinoma (UC), there is growing recognition of histologic subtypes and divergent differentiation within conventional UC. This is clinically significant, as some require modification of therapy and some are associated with more aggressive behavior. Spontaneously occurring UC in dogs has been shown to exhibit histologic and molecular features that closely resemble those of human MIBC. In this study, we evaluated 31 canine UC tumor samples for histologic subtypes and divergent differentiation. Slides were reviewed by a human uropathologist and three board-certified veterinary pathologists and assessed for expression of uroplakin III and E-cadherin. All tumors were classified as high-grade UC. Fifteen cases were identified as conventional UC. Among the remainder, eight displayed glandular differentiation, four were classified as sarcomatoid UC, two showed squamous differentiation, and one case each was classified as large nested and tubular and microcystic subtypes. In summary, this study found a higher frequency of certain histologic subtypes and divergent differentiation in canine UC--particularly sarcomatoid UC and UC with glandular differentiation--compared to previous reports in both canine UC and human MIBC. ConclusionThe relatively high prevalence of the sarcomatoid UC subtype in dogs observed in this study suggests that canine UC may serve as a valuable translational model for evaluating novel therapeutic agents, particularly for this rare and aggressive variant in humans.

pathology↗

bioRxiv2024

Pandemic Risk Assessment for a Swine Influenza A Virus in Comparative Human Substrates

Swine influenza A viruses pose a public health concern as novel and circulating strains occasionally spill over into human hosts, with the potential to cause disease. Crucial to preempting these events is the use of a threat assessment framework for human populations. However, established guidelines do not specify what animal models or in vitro substrates should be used. We completed an assessment of a contemporary swine influenza isolate, A/swine/GA/A27480/2019, using animal models and human cell substrates. Infection studies in vivo revealed high replicative ability and a pathogenic phenotype in the swine host with replication corresponding to a complementary study performed in swine primary respiratory epithelial cells. However, replication was limited in human primary cell substrates. This contrasted with our findings in the Calu-3 cell line, which demonstrated a replication profile on par with the 2009 pandemic H1N1 virus. These data suggest selection of models is important for meaningful risk assessment. Article Summary LineA novel swine influenza A virus was rigorously assessed for pandemic potential in animal models and human surrogate culture models, illustrating a wide range in potential public health risk dependent on the model utilized.

microbiology↗

bioRxiv2023

Swine influenza A virus isolates containing the pandemic H1N1 origin matrix gene elicit greater disease in the murine model

Since the 1990s, endemic North American swine influenza A viruses (swFLUAV) contained an internal gene segment constellation referred to as the triple reassortment internal gene (TRIG) cassette. In 2009, the H1N1 pandemic (pdmH1N1) virus spilled back into swine, but did not become endemic. However, the pdmH1N1 did contribute the matrix gene segment (pdmM) to the swFLUAVs circulating in the pig population; which replaced the classical swine matrix gene (swM) found in the TRIG cassette, suggesting that the pdmM has a fitness benefit. Others have shown that swFLUAV containing the pdmM have greater neuraminidase activity and transmission efficiency compared to viruses containing the swM gene segment. We hypothesized that the matrix gene could also affect disease and utilized two infection models, resistant BALB/c and susceptible DBA/2 mice, to assess swFLUAV pathogenicity. We infected BALB/c and DBA/2 mice with a panel of H1 and H3 swFLUAVs containing the swM or pdmM gene and measured lung virus titers, morbidity, mortality, and lung histopathology. H1 influenza strains containing the pdmM gene caused greater morbidity and mortality in both resistant and susceptible murine strains, while H3 swFLUAVs caused no clinical disease. However, both H1 and H3 swFLUAVs containing the pdmM replicated to higher viral titers in the lungs and pdmM containing H1 viruses induced greater histological changes compared to swM H1 viruses. While the surface glycoproteins contribute to swFLUAV pathogenicity, and other genes also influence disease, these data suggest that the origin of the matrix gene also contributes to pathogenicity of swFLUAV viruses in mice.

microbiology↗

bioRxiv2019

Randomly primed, strand-switching MinION-based sequencing for the detection and characterization of cultured RNA viruses

RNA viruses rapidly mutate, which can result in increased virulence, increased escape from vaccine protection, and false negative detection results. Targeted detection methods have a limited ability to detect unknown viruses and often provide insufficient data to detect coinfections or identify antigenic variants. Random, deep sequencing is a method that can more fully detect and characterize RNA viruses and is often coupled with molecular techniques or culture methods for viral enrichment. Viral culture coupled with third-generation sequencing were tested for the ability to detect and characterize RNA viruses. Cultures of bovine viral diarrhea virus, canine distemper virus, epizootic hemorrhagic disease virus, infectious bronchitis virus, two influenza A viruses, and porcine respiratory and reproductive syndrome virus were sequenced on the MinION platform using a random, reverse primer in a strand-switching reaction, coupled with PCR-based barcoding. Reads were taxonomically classified and used for reference-based sequence building using a stock personal computer. This method accurately detected and identified complete coding sequence genomes with a minimum of 20x coverage depth for all seven viruses, including a sample containing two viruses. Each lineage-typing region had at least 26x coverage depth for all viruses. Furthermore, analyzing the canine distemper virus sample through a pipeline devoid of canine distemper virus reference sequences modeled the ability of this protocol to detect unknown viruses. These results show the ability of this technique to detect and characterize dsRNA, negative- and positive-sense ssRNA, nonsegmented, and segmented RNA viruses.

pathology↗