101 research outputs found

    Extracellular Matrix Adjuvant for Vaccines

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    Stimulation of gastrointestinal antibody to Shiga toxin by orogastric immunization in mice

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141579/1/imcb69.pd

    Comparison of the Host Ranges and Antigenicity of Cryptosporidium parvum and Cryptosporidium wrairi from Guinea Pigs

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    Oocysts of a Cryptosporidium isolate from guinea pigs were not infectious for adult mice, but were infectious for two of three newborn calves and for suckling mice. However, oocysts isolated from calves or mice infected with guinea pig Cryptosporidium were not infectious for guinea pigs. Four isolates of C. parvum from calves were incapable of infecting weanling guinea pigs. Microscopic examination of tissue from the colon and cecum of suckling guinea pigs inoculated with C. parvum revealed sparse infection of some pups. These host range studies and previously described differences in 125 I-labeled oocyst surface protein profiles between Cryptosporidium sp. from guinea pigs and C. parvum suggest they are distinct species. We propose the name Cryptosporidium wrairi be retained. Studies with monoclonal antibodies indicate that C. wrairi and C. parvum are antigenically related.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75184/1/j.1550-7408.1992.tb01471.x.pd

    Fas/CD95 Deficiency in ApcMin/+ Mice Increases Intestinal Tumor Burden

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    Fas, a member of the tumor necrosis family, is responsible for initiating the apoptotic pathway when bound to its ligand, Fas-L. Defects in the Fas-mediated apoptotic pathway have been reported in colorectal cancer.In the present study, a variant of the Apc(Min/+) mouse, a model for the human condition, Familial Adenomatous Polyposis (FAP), was generated with an additional deficiency of Fas (Apc(Min/+)/Fas(lpr)) by cross-breeding Apc(Min/+) mice with Fas deficient (Fas(lpr)) mice. One of the main limitations of the Apc(Min/+) mouse model is that it only develops benign polyps. However, Apc(Min/+)/Fas(lpr) mice presented with a dramatic increase in tumor burden relative to Apc(Min/+) mice and invasive lesions at advanced ages. Proliferation and apoptosis markers revealed an increase in cellular proliferation, but negligible changes in apoptosis, while p53 increased at early ages. Fas-L was lower in Apc(Min/+)/Fas(lpr) mice relative to Apc(Min/+) cohorts, which resulted in enhanced inflammation.This study demonstrated that imposition of a Fas deletion in an Apc(Min/+) background results in a more aggressive phenotype of the Apc(Min/+) mouse model, with more rapid development of invasive intestinal tumors and a decrease in Fas-L levels

    Field Safety Experience with an Autologous Cancer Vaccine in Tumor-Bearing Cats: A Retrospective Study of 117 Cases (2015-2020)

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    OBJECTIVES: The aim of this study was to determine the frequency and severity of adverse events (AEs) reported from use of an adjuvanted whole-cell autologous cancer vaccine in cats with solid tumors under field conditions. METHODS: The case accession database at Torigen Pharmaceuticals was searched to identify client-owned cats that underwent biopsy or surgical resection of their primary tumor, had histologic confirmation of neoplasia and received at least one subcutaneous dose of an adjuvanted whole-cell autologous cancer vaccine. Records were reviewed for any reported AEs. RESULTS: In total, 117 cats met the inclusion criteria and received 422 doses of autologous cancer vaccine. Six (5.1%) cats had seven reported AEs, with the majority of these (85.7%) being characterized as grade 1 or 2 (mild) and resolving without medical intervention. CONCLUSIONS AND RELEVANCE: AEs were infrequent in cats treated with an adjuvanted whole-cell autologous cancer vaccine under typical field use conditions. This form of active cancer immunotherapy appears to be well tolerated by cats and may represent a treatment option for owners who are concerned about AEs associated with chemotherapy or radiotherapy. Additional studies are warranted to determine the efficacy of this form of individualized immunotherapy in cats with solid tumors

    Cross-species global and subset gene expression profiling identifies genes involved in prostate cancer response to selenium

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    BACKGROUND: Gene expression technologies have the ability to generate vast amounts of data, yet there often resides only limited resources for subsequent validation studies. This necessitates the ability to perform sorting and prioritization of the output data. Previously described methodologies have used functional pathways or transcriptional regulatory grouping to sort genes for further study. In this paper we demonstrate a comparative genomics based method to leverage data from animal models to prioritize genes for validation. This approach allows one to develop a disease-based focus for the prioritization of gene data, a process that is essential for systems that lack significant functional pathway data yet have defined animal models. This method is made possible through the use of highly controlled spotted cDNA slide production and the use of comparative bioinformatics databases without the use of cross-species slide hybridizations. RESULTS: Using gene expression profiling we have demonstrated a similar whole transcriptome gene expression patterns in prostate cancer cells from human and rat prostate cancer cell lines both at baseline expression levels and after treatment with physiologic concentrations of the proposed chemopreventive agent Selenium. Using both the human PC3 and rat PAII prostate cancer cell lines have gone on to identify a subset of one hundred and fifty-four genes that demonstrate a similar level of differential expression to Selenium treatment in both species. Further analysis and data mining for two genes, the Insulin like Growth Factor Binding protein 3, and Retinoic X Receptor alpha, demonstrates an association with prostate cancer, functional pathway links, and protein-protein interactions that make these genes prime candidates for explaining the mechanism of Selenium's chemopreventive effect in prostate cancer. These genes are subsequently validated by western blots showing Selenium based induction and using tissue microarrays to demonstrate a significant association between downregulated protein expression and tumorigenesis, a process that is the reverse of what is seen in the presence of Selenium. CONCLUSIONS: Thus the outlined process demonstrates similar baseline and selenium induced gene expression profiles between rat and human prostate cancers, and provides a method for identifying testable functional pathways for the action of Selenium's chemopreventive properties in prostate cancer

    Structure-Activity Relationship for the Oxadiazole Class of Antibacterials

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    A structure-activity relationship (SAR) for the oxadiazole class of antibacterials was evaluated by syntheses of 72 analogs and determination of the minimal-inhibitory concentrations (MICs) against the ESKAPE panel of bacteria. Selected compounds were further evaluated for in vitro toxicity, plasma protein binding, pharmacokinetics (PK), and a mouse model of methicillin-resistant Staphylococcus aureus (MRSA) infection. Oxadiazole 72c shows potent in vitro antibacterial activity, exhibits low clearance, a high volume of distribution, and 41% oral bioavailability, and shows efficacy in mouse models of MRSA infection.Fil: Boudreau, Marc A.. University of Notre Dame; Estados UnidosFil: Ding, Derong. University of Notre Dame; Estados UnidosFil: Meisel, Jayda E.. University of Notre Dame; Estados UnidosFil: Janardhanan, Jeshina. University of Notre Dame; Estados UnidosFil: Spink, Edward. University of Notre Dame; Estados UnidosFil: Peng, Zhihong. University of Notre Dame; Estados UnidosFil: Qian, Yuanyuan. University of Notre Dame; Estados UnidosFil: Yamaguchi, Takao. University of Notre Dame; Estados UnidosFil: Testero, Sebastian Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina. University of Notre Dame; Estados UnidosFil: O'Daniel, Peter I.. University of Notre Dame; Estados UnidosFil: Leemans, Erika. University of Notre Dame; Estados UnidosFil: Lastochkin, Elena. University of Notre Dame; Estados UnidosFil: Song, Wei. University of Notre Dame; Estados UnidosFil: Schroeder, Valerie A.. University of Notre Dame; Estados UnidosFil: Wolter, William R.. University of Notre Dame; Estados UnidosFil: Suckow, Mark A.. University of Notre Dame; Estados UnidosFil: Mobashery, Shahriar. University of Notre Dame; Estados UnidosFil: Chang, Mayland. University of Notre Dame; Estados Unido

    Structure-Activity Relationship for the Oxadiazole Class of Antibiotics

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    The structure-activity relationship (SAR) for the newly discovered oxadiazole class of antibiotics is described with evaluation of 120 derivatives of the lead structure. This class of antibiotics was discovered by in silico docking and scoring against the crystal structure of a penicillin-binding protein. They impair cell-wall biosynthesis and exhibit activities against the Gram-positive bacterium Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA) and vancomycin-resistant and linezolid-resistant S. aureus. 5-(1H-Indol-5-yl)-3-(4-(4-(trifluoromethyl)phenoxy)phenyl)-1,2,4-oxadiazole (antibiotic 75b) was efficacious in a mouse model of MRSA infection, exhibiting a long half-life, a high volume of distribution, and low clearance. This antibiotic is bactericidal and is orally bioavailable in mice. This class of antibiotics holds great promise in recourse against infections by MRSA.Fil: Spink, Edward. University of Notre Dame-Indiana; Estados UnidosFil: Ding, Derong. University of Notre Dame-Indiana; Estados UnidosFil: Peng, Zhihong. University of Notre Dame-Indiana; Estados UnidosFil: Boudreau, Marc A.. University of Notre Dame-Indiana; Estados UnidosFil: Leemans, Erika. University of Notre Dame-Indiana; Estados UnidosFil: Lastochkin, Elena. University of Notre Dame-Indiana; Estados UnidosFil: Song, Wei. University of Notre Dame-Indiana; Estados UnidosFil: Lichtenwalter, Katerina. University of Notre Dame-Indiana; Estados UnidosFil: O’Daniel, Peter I.. University of Notre Dame-Indiana; Estados UnidosFil: Testero, Sebastian Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina. University of Notre Dame-Indiana; Estados UnidosFil: Pi, Hualiang. University of Notre Dame-Indiana; Estados UnidosFil: Schroeder, Valerie A.. University of Notre Dame-Indiana; Estados UnidosFil: Wolter, William R.. University of Notre Dame-Indiana; Estados UnidosFil: Antunes, Nuno T.. University of Notre Dame-Indiana; Estados UnidosFil: Suckow, Mark A.. University of Notre Dame-Indiana; Estados UnidosFil: Vakulenko, Sergei. University of Notre Dame-Indiana; Estados UnidosFil: Chang, Mayland. University of Notre Dame-Indiana; Estados UnidosFil: Mobashery, Shahriar. University of Notre Dame-Indiana; Estados Unido

    Proceedings of Abstracts Engineering and Computer Science Research Conference 2019

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    © 2019 The Author(s). This is an open-access work distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. For further details please see https://creativecommons.org/licenses/by/4.0/. Note: Keynote: Fluorescence visualisation to evaluate effectiveness of personal protective equipment for infection control is © 2019 Crown copyright and so is licensed under the Open Government Licence v3.0. Under this licence users are permitted to copy, publish, distribute and transmit the Information; adapt the Information; exploit the Information commercially and non-commercially for example, by combining it with other Information, or by including it in your own product or application. Where you do any of the above you must acknowledge the source of the Information in your product or application by including or linking to any attribution statement specified by the Information Provider(s) and, where possible, provide a link to this licence: http://www.nationalarchives.gov.uk/doc/open-government-licence/version/3/This book is the record of abstracts submitted and accepted for presentation at the Inaugural Engineering and Computer Science Research Conference held 17th April 2019 at the University of Hertfordshire, Hatfield, UK. This conference is a local event aiming at bringing together the research students, staff and eminent external guests to celebrate Engineering and Computer Science Research at the University of Hertfordshire. The ECS Research Conference aims to showcase the broad landscape of research taking place in the School of Engineering and Computer Science. The 2019 conference was articulated around three topical cross-disciplinary themes: Make and Preserve the Future; Connect the People and Cities; and Protect and Care
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