Dr. Linda Susan Mansfield |
|
Michigan State University College of Veterinary Medicine Large Animal Clinical Sciences and Microbiology and Molecular Genetics Professor Michigan State University College of Veterinary Medicine Large Animal Clinical Sciences and Microbiology and Molecular Genetics Associate Chair for Research and Graduate Studies |  |
Mailing Address181 Food Safety and Toxicology Building Department of Large Animal Clinical Sciences College of Veterinary Medicine East Lansing, Michigan 48824United States | Contact Information |
Qualifications
Ph.D., University of Pennsylvania, Parasitology/Immunology, 1990.
V.M.D., University of Pennsylvania, Veterinary Medicine, 1986.
M.S., University of Delaware, Virology, 1980.
B.S., University of Delaware, Biology, 1975.
Expertise and Research Interests
COMPARATIVE ENTERIC DISEASES LABORATORY- My laboratory studies enteric pathogens that are important causes of disease in humans or animals.
Project 1 - Murine models of Campylobacter jejuni colonization and enteritis. C. jejuni is a globally distributed human pathogen, a leading cause of food borne enteritis, and has been linked to chronic neurological and joint diseases. To combat this pathogen, it is important to develop murine models of enteritis induced by primary C. jejuni challenge employing mice with a genetic background and immune bias that enhances susceptibility. In 3 years, we will deliver: 1) an SOP for infection of IL-10 knockout mice with C. jejuni strains, and 2) reproducible mouse models for C. jejuni colonization, and C. jejuni enteritis. We will conduct 4 experiments. Exp#1: Genetic Background. We will test inbred IL-10 KO mice of different genetic backgrounds (e.g. C57BL/6, B6.129P2, NOD, C3H/HeJBir, C3Bir.129P2(B6)) for susceptibility to C. jejuni colonization and enteritis. Exp#2: Dose Response. We will determine the dose-response of C57BL/6 IL-10 -/- mice given C. jejuni. Here, we will challenge groups of mice orally with C. jejuni 11168 in 10-fold dilutions and quantify colonization and enteritis levels using a C. jejuni specific RT-PCR assay to determine the optimal dilution for subsequent studies. Exp#3: Time Course. We will determine the time-course for colonization and enteritis to develop in C57BL/6 IL-10 -/- mice given C. jejuni. Here, groups of mice will be challenged with C. jejuni 11168 to quantify levels of colonization and enteritis over time. Exp#4: Mouse Adaptation. We will determine the effect of repeated mouse passage on the ability of C. jejuni to colonize the mouse GI tract and to cause enteritis. In all experiments, the two outcomes assessed will be colonization or enteritis (disease/pathology).
Project 2 - Mid-Career Investigator in Mouse Pathobiology. "Testing parasite products as cures for Inflammatory Bowel Disease". The overall goal is 1) to develop mouse models to test parasite products as cures for Inflammatory Bowel Disease, and 2) to foster veterinarians to enter the research arena. Recently, I have expanded my focus within Comparative Medicine from large animal models of human and animal enteric diseases to murine models of enteric diseases.
Project 2 experimental focus - Worm mediated control of Inflammatory Bowel Disease. IBD is a serious chronic intestinal inflammatory disorder, afflicting 6/100,000 adults in the US. Two forms are recognized: ulcerative colitis (UC) and Crohn's disease (CD). Information in the literature suggests that multiple factors may interact to produce IBD: host genetics, adaptive cellular host immune responses, and pathogens and normal flora of the intestinal tract that stimulate innate mucosal immune responses through pattern-recognition signaling pathways. Current treatments are aimed at reducing inflammation and postponing surgery, which becomes necessary in about 75% of cases. These treatments are seldom effective over the long term. Recently Dr. Joel Weinstock and colleagues at the University of Iowa have had success in using deliberate infection with the helminth Trichuris suis to treat patients whose disease was refractory to standard treatments. The mechanism by which T. suis infection ameliorates IBD is unknown. However, there is evidence that parasites such as T. suis act to moderate the inflammatory responses involved in the development of IBD by triggering anti-inflammatory mechanisms that include the release of specific anti-inflammatory cytokines, induction of specific anti-inflammatory responses in dendritic (DC) cells, and induction of specific responses of T regulatory cells that shift the Th1/Th2 cytokine balance toward an anti-inflammatory milieu. The long-term goal of our research is to understand how T. suis helps resolve IBD in humans. In this project, we will challenge cell lines with defined antigens/products from T. suis to determine which are responsible for this immunomodulatory phenomenon observed in human patients. Also, we will validate a new mouse model of lower bowel inflammation and take the first steps to test Trichuris therapy in this model. The first hypothesis to be tested is that T. suis products elicit anti-inflammatory cytokines and T helper cell mediators that down-regulate cell-mediated responses that cause IBD in some humans. The second hypothesis to be tested is that a T. suis product or combination of products can be found that will produce the same effect as whole worms to reduce inflammation. The overall rationale is that swine and mice infected with T. suis or T. muris, respectively, exhibit anti-inflammatory cytokine profiles. Cultured epithelial cells exposed to excretory secretory products (ESP) from Trichuris also exhibit anti-inflammatory cytokine profiles. The specific antigen/product basis that elicits these responses is not fully known. Until the products are isolated and characterized in cell culture and animal models, it will not be known whether a specific Trichuris molecule(s) is responsible for the majority of the anti-inflammatory signature seen clinically and whether it could be used for therapeutic purposes.
Project 3 - Characterization of the colonic microbial ecology in diarrheic dogs. Diagnosis and treatment of infectious bacterial diarrheas only rarely results in a true understanding of the etiology and underlying mechanisms of pathogenesis. Empiric evidence for causation comes from antibiotic therapy, but this ignores the fact that antibiotics are broad in spectrum and have dramatic effects on the communities of microorganisms necessary for a healthy bowel. Pathogens can be identified by molecular diagnostic procedures, but definitive antemortem causation is always hypothetical. Our long-term objective is to decrease diarrhea in dogs due to infectious etiologies and to assess the contribution of the enteric microbiota (microflora of the colon) in the pathogenesis of diarrhea during a diarrheic episode. We expect information generated to be 1) a small step toward understanding the contribution of the microbiota to colon health and disease, and 2) preliminary data to seek further funding to study "the black box of the bowel" in a scientifically rigorous manner. This is now possible because of the advent of methodologies to evaluate the complexity of the bowel microbiota using non-culture based means by documenting populations of microorganisms using a genomic approach and ribosomal database tools. We expect that there are common mucosal physiological conditions (normal homeostatic and abnormal due to pathogens and antibiotic treatments) that, if known, could dramatically change the way we approach management and treatment of enteric infections in small animals and, comparatively, humans. Our Specific Aims are 1) to collect and analyze fecal specimens from dogs with diarrhea for enteric pathogens using traditional molecular diagnostic methods, 2) to determine the major constituents of the microbiota in these specimens, and 3) to assess the effect of antibiotic therapy on the microbiota and clinical outcome. Methods. DNA from feces will be screened by PCR for common pathogens. Using terminal restriction fragment polymorphism (T-RFLP), bacterial DNA from feces will be PCR amplified using universal 16S rRNA gene primers with a fluorescent probe. PCR products will be digested separately with several 4-cutter restriction enzymes, resulting fragments separated by electrophoresis on an automated ABI Prism sequencer, and GeneScan software used to compare peak patterns. Identity of bacterial phylogenetic groups detected will be determined using a web-based phylogenetic analysis tool. A dissimilarity index based on the areas of peaks in the electropherograms will be calculated for all pairs of profiles and UPGMA cluster analysis conducted. Analysis will show whether patterns from healthy, diarrheic, or antibiotic treated dogs can be distinguished and degree of variation in fecal microbiota between individuals within groups.
Project 4 - Pathogenesis of Sarcocystis neurona. We have made significant progress studying the biology and pathogenesis of Sarcocystis neurona, the agent of Equine Protozoal Myeloencephalitis in horses. This common protozoan parasite causes severe neurological disease in horses in the new world. We have developed a highly sensitive and specific western blot test that is in use as an ante mortem test for the immune response to the parasite in horses with clinical disease. This test was applied in an epidemiological study to determine the seroprevalence of antibodies to S. neurona in horses in Michigan using a cross-sectional design. Current projects involve development of an antigen test, vaccine, lifecycle studies, in vitro methods to examine S. neurona pathogenesis, and molecular evolutionary methods to examine relatedness between closely related Apicomplexan organisms that cause disease. Development of an antigen test to detect S. neurona will help to solve the problem of diagnosis in the face of vaccination with the recently released whole cell vaccine. The latest grant funding from the Grayson Foundation enabled us to examine genetic relatedness of cyst forming coccidia (Sarcocystis, Neospora, Toxoplasma and Besnoitia) and the role that sexual recombination plays in the observed diversity within these genera.
Future Aims.
"Proof of concept and method standardization for screening for Campylobacter jejuni virulence attributes in murine models", term 4/20/2007 to 4/19/2010, funded.
Project 1 - Murine models of Campylobacter jejuni colonization and enteritis. C. jejuni is a globally distributed human pathogen, a leading cause of food borne enteritis, and has been linked to chronic neurological and joint diseases. To combat this pathogen, it is important to develop murine models of enteritis induced by primary C. jejuni challenge employing mice with a genetic background and immune bias that enhances susceptibility. In 3 years, we will deliver: 1) an SOP for infection of IL-10 knockout mice with C. jejuni strains, and 2) reproducible mouse models for C. jejuni colonization, and C. jejuni enteritis. We will conduct 4 experiments. Exp#1: Genetic Background. We will test inbred IL-10 KO mice of different genetic backgrounds (e.g. C57BL/6, B6.129P2, NOD, C3H/HeJBir, C3Bir.129P2(B6)) for susceptibility to C. jejuni colonization and enteritis. Exp#2: Dose Response. We will determine the dose-response of C57BL/6 IL-10 -/- mice given C. jejuni. Here, we will challenge groups of mice orally with C. jejuni 11168 in 10-fold dilutions and quantify colonization and enteritis levels using a C. jejuni specific RT-PCR assay to determine the optimal dilution for subsequent studies. Exp#3: Time Course. We will determine the time-course for colonization and enteritis to develop in C57BL/6 IL-10 -/- mice given C. jejuni. Here, groups of mice will be challenged with C. jejuni 11168 to quantify levels of colonization and enteritis over time. Exp#4: Mouse Adaptation. We will determine the effect of repeated mouse passage on the ability of C. jejuni to colonize the mouse GI tract and to cause enteritis. In all experiments, the two outcomes assessed will be colonization or enteritis (disease/pathology).
Project 2 - Mid-Career Investigator in Mouse Pathobiology. "Testing parasite products as cures for Inflammatory Bowel Disease". The overall goal is 1) to develop mouse models to test parasite products as cures for Inflammatory Bowel Disease, and 2) to foster veterinarians to enter the research arena. Recently, I have expanded my focus within Comparative Medicine from large animal models of human and animal enteric diseases to murine models of enteric diseases.
Project 2 experimental focus - Worm mediated control of Inflammatory Bowel Disease. IBD is a serious chronic intestinal inflammatory disorder, afflicting 6/100,000 adults in the US. Two forms are recognized: ulcerative colitis (UC) and Crohn's disease (CD). Information in the literature suggests that multiple factors may interact to produce IBD: host genetics, adaptive cellular host immune responses, and pathogens and normal flora of the intestinal tract that stimulate innate mucosal immune responses through pattern-recognition signaling pathways. Current treatments are aimed at reducing inflammation and postponing surgery, which becomes necessary in about 75% of cases. These treatments are seldom effective over the long term. Recently Dr. Joel Weinstock and colleagues at the University of Iowa have had success in using deliberate infection with the helminth Trichuris suis to treat patients whose disease was refractory to standard treatments. The mechanism by which T. suis infection ameliorates IBD is unknown. However, there is evidence that parasites such as T. suis act to moderate the inflammatory responses involved in the development of IBD by triggering anti-inflammatory mechanisms that include the release of specific anti-inflammatory cytokines, induction of specific anti-inflammatory responses in dendritic (DC) cells, and induction of specific responses of T regulatory cells that shift the Th1/Th2 cytokine balance toward an anti-inflammatory milieu. The long-term goal of our research is to understand how T. suis helps resolve IBD in humans. In this project, we will challenge cell lines with defined antigens/products from T. suis to determine which are responsible for this immunomodulatory phenomenon observed in human patients. Also, we will validate a new mouse model of lower bowel inflammation and take the first steps to test Trichuris therapy in this model. The first hypothesis to be tested is that T. suis products elicit anti-inflammatory cytokines and T helper cell mediators that down-regulate cell-mediated responses that cause IBD in some humans. The second hypothesis to be tested is that a T. suis product or combination of products can be found that will produce the same effect as whole worms to reduce inflammation. The overall rationale is that swine and mice infected with T. suis or T. muris, respectively, exhibit anti-inflammatory cytokine profiles. Cultured epithelial cells exposed to excretory secretory products (ESP) from Trichuris also exhibit anti-inflammatory cytokine profiles. The specific antigen/product basis that elicits these responses is not fully known. Until the products are isolated and characterized in cell culture and animal models, it will not be known whether a specific Trichuris molecule(s) is responsible for the majority of the anti-inflammatory signature seen clinically and whether it could be used for therapeutic purposes.
Project 3 - Characterization of the colonic microbial ecology in diarrheic dogs. Diagnosis and treatment of infectious bacterial diarrheas only rarely results in a true understanding of the etiology and underlying mechanisms of pathogenesis. Empiric evidence for causation comes from antibiotic therapy, but this ignores the fact that antibiotics are broad in spectrum and have dramatic effects on the communities of microorganisms necessary for a healthy bowel. Pathogens can be identified by molecular diagnostic procedures, but definitive antemortem causation is always hypothetical. Our long-term objective is to decrease diarrhea in dogs due to infectious etiologies and to assess the contribution of the enteric microbiota (microflora of the colon) in the pathogenesis of diarrhea during a diarrheic episode. We expect information generated to be 1) a small step toward understanding the contribution of the microbiota to colon health and disease, and 2) preliminary data to seek further funding to study "the black box of the bowel" in a scientifically rigorous manner. This is now possible because of the advent of methodologies to evaluate the complexity of the bowel microbiota using non-culture based means by documenting populations of microorganisms using a genomic approach and ribosomal database tools. We expect that there are common mucosal physiological conditions (normal homeostatic and abnormal due to pathogens and antibiotic treatments) that, if known, could dramatically change the way we approach management and treatment of enteric infections in small animals and, comparatively, humans. Our Specific Aims are 1) to collect and analyze fecal specimens from dogs with diarrhea for enteric pathogens using traditional molecular diagnostic methods, 2) to determine the major constituents of the microbiota in these specimens, and 3) to assess the effect of antibiotic therapy on the microbiota and clinical outcome. Methods. DNA from feces will be screened by PCR for common pathogens. Using terminal restriction fragment polymorphism (T-RFLP), bacterial DNA from feces will be PCR amplified using universal 16S rRNA gene primers with a fluorescent probe. PCR products will be digested separately with several 4-cutter restriction enzymes, resulting fragments separated by electrophoresis on an automated ABI Prism sequencer, and GeneScan software used to compare peak patterns. Identity of bacterial phylogenetic groups detected will be determined using a web-based phylogenetic analysis tool. A dissimilarity index based on the areas of peaks in the electropherograms will be calculated for all pairs of profiles and UPGMA cluster analysis conducted. Analysis will show whether patterns from healthy, diarrheic, or antibiotic treated dogs can be distinguished and degree of variation in fecal microbiota between individuals within groups.
Project 4 - Pathogenesis of Sarcocystis neurona. We have made significant progress studying the biology and pathogenesis of Sarcocystis neurona, the agent of Equine Protozoal Myeloencephalitis in horses. This common protozoan parasite causes severe neurological disease in horses in the new world. We have developed a highly sensitive and specific western blot test that is in use as an ante mortem test for the immune response to the parasite in horses with clinical disease. This test was applied in an epidemiological study to determine the seroprevalence of antibodies to S. neurona in horses in Michigan using a cross-sectional design. Current projects involve development of an antigen test, vaccine, lifecycle studies, in vitro methods to examine S. neurona pathogenesis, and molecular evolutionary methods to examine relatedness between closely related Apicomplexan organisms that cause disease. Development of an antigen test to detect S. neurona will help to solve the problem of diagnosis in the face of vaccination with the recently released whole cell vaccine. The latest grant funding from the Grayson Foundation enabled us to examine genetic relatedness of cyst forming coccidia (Sarcocystis, Neospora, Toxoplasma and Besnoitia) and the role that sexual recombination plays in the observed diversity within these genera.
Future Aims.
"Proof of concept and method standardization for screening for Campylobacter jejuni virulence attributes in murine models", term 4/20/2007 to 4/19/2010, funded.
Other Expertise
Data Base Contributions = Parasitology/addition of parasite material material to the US National Parasite Collection
DNA Sequence = Major exsheathment protection of ''Haemonchus contortus'' oligonucleotide sequence, GenBank accession number 18330
Production of swine cytokine competitors for RT-PCR assay containing cloned swine sequences from IL-2, IL-4, IL-10, TNF alpha, IFN gamma, CD3, and HPRT genes (1995)
Swine cytokine IL-10 gene sequence. GenBank accession number HPRTSUS U69731
Gene sequences from Cyst forming coccidians, Sarcocystis neurona and Besnoitia species
DNA Sequence = Major exsheathment protection of ''Haemonchus contortus'' oligonucleotide sequence, GenBank accession number 18330
Production of swine cytokine competitors for RT-PCR assay containing cloned swine sequences from IL-2, IL-4, IL-10, TNF alpha, IFN gamma, CD3, and HPRT genes (1995)
Swine cytokine IL-10 gene sequence. GenBank accession number HPRTSUS U69731
Gene sequences from Cyst forming coccidians, Sarcocystis neurona and Besnoitia species
Future Research
Our long term goal is to eliminate disease due to enteric pathogens through vaccine mediated control. With food borne pathogens like Campylobacter jejuni this often means vaccinating animals to protect people. We are currently developing genomic and proteomic methodologies to examine differences in Campylobacter strains, and Campylobacter-host interactions. This information will allow us to design vaccines that will be effective on a population wide scale.
Industrial Relevance
We commonly interact with the pharmaceutical industry to develop better methods for diagnosis and prevention of diseases in animals.
Keywords
COS Keywords:
Animal Models, Food Safety, Genetics, Immunology, Infectious Diseases Or Agents, Microbiology, Molecular Biology, Parasitology, Pathogenesis, Veterinary Medicine, Virology.Additional Terms:
Campylobacter Jejuni, Enteric Disease, Food Safety, Immunomodulation, Inflammatory Bowel Disease, Trichuris.Languages
(Reading, Writing, Speaking)
German: (Basic, Basic, Basic)
Memberships
American Association for the Advancement of Science
American Association of Veterinary Parasitologists
American Society for Microbiology
American Society of Parasitologists
American Veterinary Medical Association
Conference of Research Workers in Animal Diseases
World Association for the Advancement of Veterinary Parasitology
Honors and Awards
2004-2005,
President,
American Association of Veterinary Parasitologists
2004, Nominated for the Norden Award for Teaching Excellence,
College of Veterinary Medicine, Michigan State University
2003, Excellence in Teaching Award,
College of Veterinary Medicine,
Michigan State University
2003, Vice President,
American Association of Veterinary Parasitologists
2003-2004,
President Elect,
American Association of Veterinary Parasitologists
2001-2005,
Co-Editor-in-Chief, Veterinary Parasitology,
2000-2003,
Executive Council Member,
American Association of Parasitologists
2000, Pfizer Award for Research Excellence,
Pfizer Inc
1997, Chair of the Immunology Section,
Conference of Research Workers on Animal Diseases
1996, Excellence in Teaching Award,
College of Veterinary Medicine,
Michigan State University
Previous Positions
1999, Associate Professor,
Michigan State University,
College of Veterinary Medicine,
Microbiology and Molecular Genetics,
Large Animal Clinical Sciences
1994-1999, Assistant Professor,
Michigan State University,
College of Veterinary Medicine,
Microbiology
1990-1994, Postdoctoral Fellow,
United States Department of Agriculture,
Molecular Biology,
Agriculture Research Service
1982-1990, Research Fellow,
University of Pennsylvania,
College of Veterinary Medicine
Patents
Positive Selection in the immuno-dominant surface antigen 1(SAG1) of Sarcocystis neurona, agent of EPM: potential as a diagnostic reagent and as a component of a subunit vaccine,
Patent Number: ID#04-089,
2004,
Institution,
United States of America.
A rapid method to detect fluoroquinolone resistant Campylobacter jejuni in environmental samples,
Patent Number: 6355435 S.N. 09/656286,
2002,
Institution-owned,
.
Development of an antigen test to detect Sarcocystis neurona in horse serum and cerebrospinal fluid,
Patent Number: 6344337 (ID99-021),
2002,
Institution-owned,
United States of America.
A rapid method to detect and enumerate Campylobacter jejuni in environmental samples with high specificity,
Patent Number: 6355435 S.N. 09/656286,
2002,
Institution-owned,
United States of America.
A rapid method to detect fluoroquinolone resistant Campylobacter jejuni in environmental samples,
Patent Number: ID# 99-0042,
2002,
Institution,
United States of America.
Immunoassay for Equine Protozoal Myeloencephalitis in Horses,
Patent Number: 6153394 S.N. 09/156954,
2001,
Institution-owned,
United States of America.
An antimicrobial agent secreted by Trichuris suis,
Patent Number: ID# 00-018,
1999,
Institution,
United States of America.
Funding Received
- National Institutes of Health, National Institute of Allergy and Infectious Diseases Branch, Food and Waterborne Diseases Integrated Research Network - Microbiology Research Unit: Proof of concept and method standardization for screening for Campylobacter jejuni virulence attributes in murine models, $729,470, 2007 to 2010.
- National Institutes of Health, National Center for Research Resources (NCRR): Mid-Career Investigator in Mouse Pathobiology, Tesing Parasite Products as Cures for Inflammatory Bowel Disease, $350,000, 2006 to 2011.
- Michigan State University, College of Veterinary Medicine: Companion Animal Fund Grant, Characterization of the colonic microbial ecology in diarrheic dogs, $25,000, 2005 to 2007.
- National Institutes of Health (NIH): Food and Waterborne Diseases Integrated Research Network - Microbiology Research Unit, $10.3 m, 2004 to 2011.
- Research Council for Veterinary and Agricultural Sciences, Copenhagen, Denmark: Do intestinal worms impair the protective effect of vaccines in pigs?, $397,272, 2004 to 2007.
- Michigan State University Intellectual Property Office: Development of an Antigen Test to detect Sarcocystis neurona the agent causing Equine Protozoal Myeloencephalitis (EPM), $10,000, 2004 to 2005.
- National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases: Murine models of Campylobacter jejuni colonization and enteritis, $585,577, 2004 to 2007.
- Grayson Jockey Club Research Foundation: Molecular Epidemiology and Evolution of Sarcocystis Neurona, agent of EPM, $52,455, 2003 to 2005.
- Denmark Research Council, Sabbatical Leave Funding: Interactions between Campylobacters and parasites in swine under organic rearing conditions, $95,000, 2003 to 2005.
- Center for Emerging Infectious Diseases, College of Veterinary Medicine, Michigan State University: Development of new molecular methodologies for enteric pathogens, $100,000, 2003 to 2004.
- Denmark Research Council, Sabbatical Leave Funding: Interactions between Campylobacters and parasites in swine under organic rearing conditions, $95,000, 2003 to 2005.
- Integrated Food Safety Initiative: Interventions for controlling antimicrobial resistance of Salmonella and Campylobacter in dairy cattle for Salmonella and Campylobacter infections and drug resistance in dairy cattle, $599,999, 2002 to 2005.
- United States Department of Agriculture, Animal Health Formula Funds Program: Establishment of expression proteomics methodology for the food borne pathogen Campylobacter jejuni, $15,000, 2002 to 2003.
- Pfizer Inc: Does Strongid C reduce the risk of Sarcocystis neurona infection or colic in horses, $291,278, 2000 to 2004.
- United States Department of Agriculture (USDA): Addressing microbial threats to human food safety, National Needs Fellowship Program, $345,000, 2000 to 2007.
- Fort Dodge Corporation Grant: Improvements to diagnosis of equine protozoal myeloencephalitis to accommodate vaccination for Sarcocystis neurona, $62,246, 2000 to 2003.
- National Food Safety and Toxicology Center Grant: Development of genetic tools to study how Campylobacter jejuni causes Guillain Barre Syndrome, $35,800, 1999 to 2002.
- United States Department of Agriculture, NRICGP Program: Risk factors for Salmonella and Campylobacter infections and drug resistance in dairy cattle, $981,367, 1999 to 2002.
- National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases: Host Factors Mediate Invasion by Campylobacter jejuni, $350,000, 1997 to 2002.
Publications
- Fong, T.T., Mansfield, L.S., Wilson, D.L., Scwab, D.J., Molloy, S.L. (2007) Massive Microbiological Groundwater Contamination Associated with a Waterborne Outbreak in Lake Erie, South Bass Island, OH, Journal of Environmental Health Perspectives, 115 (6), 856-864
- Jones KM, Mansfield LS, Campylobacter jejuni invades distal colonic lymphoglandular complexes causing upregulation of proinflammatory cytokines in a swine rectal challenge model, Veterinary Immunology and Immunopathology, Submitted, 2007
- Mansfield, L.S., Bell, J.A., Wilson, D.L., Murphy, A.J., Elsheikha, H.M., Rathinam, V.A., Fierro, B.R., Linz, J.E., Young, V.B. (2006) C57BL/6 and congenic interleukin-10 deficient mice can serve as models of Campylobacter jejuni colonization and enteritis, Infection and Immunity, 75 (3), 1099-115
- Elsheikha, H.M., Schott, H.C., Mansfield, L.S. (2006) Genetic Variation Among Sarcocystis neurona Agent of Protozoal Myeloencephalitis As Revealed by AFLP Markers, Infection and Immunity 74(6):3448-54., 74 (6), 3448-3454
- Halbert, L.W., Kaneene, J.B., Ruegg, P.L., Warnick, L.D., Wells, S.J., Mansfield, L.S., Fossler, C.P., Campbell, A.M., Geiger-Zwald, A.M., Evaluation of antimicrobial susceptibility patterns in Campylobacter spp. isolated from dairy cattle and farms managed organically and conventionally in the midwestern and northeastern United States, J Am Vet Med Assoc, 228(7), 1074-81, 1 Apr 2006
- Halbert, L.W., Kaneene, J.B., Ruegg, P.L., Warnick, L.D., Wells, S.J., Mansfield, L.S., Fossler, C.P., Campbell, A.M., Geiger-Zwald, A.M. (2006) Evaluation of antimicrobial susceptibility patterns in Campylobacter spp. isolated from dairy cattle and farms managed organically and conventionally in the midwestern and northeastern United States, Journal of the American Veterinary Medical Association, 228 (7), 1074-81
- Halbert, L.W., Kaneene, J.B., Linz, J.E., Mansfield, L.S., Wilson, D.L., Ruegg, P.L., Warnick, L.D., Wells, S.J., Fosler, C.P., Campbell, A.M., Geiger-Zwald, A.M., Genetic Mechanisms Contributing to Reduced Tetracycline Susceptibility of Campylobacter Isolated From Organic and Conventional Dairy Farms in the Midwestern and Northeastern United States, Journal of Food Protection, 69(3), 482-488, 2005
- Mullaney T, Murphy AJ, Kiupel M, Bell JA, Rossano MG, Mansfield LS (Oct 2005) Evidence to support horses as natural intermediate hosts for Sarcocystis
neurona., Veterinary Parasitology, 133 (1), 27-36
- Parthasarathy G, Mansfield LS (Aug 2005) Trichuris suis excretory secretory products (ESP) elicit interleukin-6
(IL-6) and IL-10 secretion from intestinal epithelial cells
(IPEC-1)., Veterinary Parasitology, 131 (3-4), 317-24
- Elsheikha HM, Murphy AJ, Mansfield LS (Jul 2005) Phylogenetic congruence of Sarcocystis neurona Dubey et al., 1991
(Apicomplexa: Sarcocystidae) in the United States based on sequence
analysis and restriction fragment length polymorphism
(RFLP)., Systematic Parasitology, 61 (3), 191-202
- Elsheikha HM, Rosenthal BM, Mansfield LS (Apr 2005) Dexamethasone treatment induces susceptibility of outbred Webster mice to
experimental infection with Besnoitia darlingi isolated from opossums
(Didelphis virginiana)., Parasitology Research, 95 (6), 413-9
- Rossano MG, Schott HC 2nd, Murphy AJ, Kaneene JB, Sellon DC, Hines MT, Hochstatter T, Bell JA, Mansfield LS, Parasitemia in An Immunocompetent Horse Experimentally Challenged With Sarcocystis Neurona Sporocysts., Veterinary Parasitology, 127(1), 3-8, Jan 2005
- Young VB and Mansfield LS, Campylobacter Infection-Clinical Context., In: Campylobacter Jejuni: New Perspectives in Molecular and Cellular Biology, Horizon press, 1-12, 2005
- Elsheikha HM, Murphy AJ and Mansfield LS, Phylogenetic Congruence of Sarcocystis Neurona (Apicomplexa: Sarcocystidae) in the United States Based on Sequence Analysis and Restriction Fragment Length Polymorphism (RFLP), Systematic Parasitology, 61(3), 191-202, 2005
- Parthasarathy G and Mansfield LS, Trichuris Suis Excretory Secretory Products (ESP) Elicit Interleukin-6 (IL-6) and IL-10 Secretion From Intestinal Epithelial Cells (IPEC-1), Veterinary Parasitology, 131(2005), 317-324, 2005
- Elsheikha HM, Rosenthal BM, Mansfield LS, Dexamethasone Treatment Induces Susceptibility of Outbred Webster Mice to Experimental Infection With Besnoitia Darlingi Isolated From Opossums (Didelphis Virginiana), Parasitology Research, 95(6), 413-419, 2005
- Rossano MG, Schott II HC, Kaneene JB, Murphy AJ, Kruttlin EA, Hines MT, Sellon DC, Patterson JS, Elsheikha HM, Dubey JP, Mansfield LS, Effect of Daily Pyrantel Tartrate in Preventing Sarcocystis Neurona Infection in Experimentally Challenged Horses, American Journal of Veterinary Research, 66, 846-852, 2005
- Elsheikha HM, Lacher DW, Mansfield LS, Phylogenetic Relationships of Sarcocystis Neurona of Horse and Opossum to Other Cyst-forming Coccidia Deduced From SSUr RNA Gene Sequences, Parasitology Research, May 2005, 1-26, 2005
- Elsheikha HM, Mackenzie CD, Rosenthal BM, Marteniuk JV, Steficick B, Windsor S, and Mansfield LS, An Outbreak of Besnoitiosis in Miniature Donkeys (Equus Asinus), Journal of Parasitology, In Press, 2005
- Elsheikha HM, Schott HC, and Mansfield LS, Genetic Variation Among Sarcocystis Neurona Agent of Protozoal Myeloencephalitis As Revealed By AFLP Markers, Infection and Immunity, Submitted, 2005
- Parthasarathy ,G., Mansfield, L.S., Recombinant IL-4 (rIL-4) Enhances Campylobacter Jejuni Invasion of Intestinal Pig Epithelial Cells (IPEC-1), Veterinary Parasitology, 131(2005), 317-324, 2005
- Halbert LW, Kaneene JB, Mansfield LS, Ruegg PL, Warnick LD, Wells SJ, Fossler CP, Campbell AM, Geiger-Zwald AM, The Comparison of Automated Microbroth Dilution and Agar Dilution for Antimicrobial Susceptibility of Campylobacter Jejuni Isolated From Dairy Sources, Journal of Antimicrobial Chemotherapy, 56(2005), 686-691, 2005
- Rossano MG, Schott HC 2nd, Murphy AJ, Kaneene JB, Sellon DC, Hines MT, Hochstatter T, Bell JA, Mansfield LS (Jan 2005) Parasitemia in an immunocompetent horse experimentally challenged with
Sarcocystis neurona sporocysts., Veterinary Parasitology, 127 (1), 3-8
- Mansfield LS, Gajadhar AA, Cyclospora Cayetanensis, a Food- and Waterborne Coccidian Parasite., Veterinary Parasitology, 126(1-2), 73-90, Dec 2004
- Elsheikha HM, Mansfield LS, Sarcocystis Neurona Major Surface Antigen Gene 1 (SAG1) Shows Evidence of Having Evolved Under Positive Selection Pressure., Parasitology Research, 94(6), 452-9, Dec 2004
- Elsheikha HM, Mansfield LS (Dec 2004) Sarcocystis neurona major surface antigen gene 1 (SAG1) shows evidence of
having evolved under positive selection pressure., Parasitology Research, 94 (6), 452-9
- Elsheikha HM, Murphy AJ, Mansfield LS, Prevalence of and Risk Factors Associated With the Presence of Sarcocystis Neurona Sporocysts in Opossum (Didelphis Virginiana) From Michigan: a Retrospective Study., Veterinary Parasitology, 125(3-4), 277-86, Nov 2004
- Mansfield LS, Gauthier DT, Lymphoglandular Complexes Are Important Colonic Sites for Immunoglobulin a Induction Against Campylobacter Jejuni in a Swine Disease Model., Comparative Medicine, 54(5), 514-23, Oct 2004
- Muccio JL, Grooms DL, Mansfield LS, Wise AG, Maes RK, Evaluation of Two Rapid Assays for Detecting Cryptosporidium Parvum in Calf Feces., Journal of the American Veterinary Medical Association, 225(7), 1090-2, Oct 2004
- Muccio JL, Grooms DL, Mansfield LS, Wise AG, Maes RK (Oct 2004) Evaluation of two rapid assays for detecting Cryptosporidium parvum in
calf feces., Journal of the American Veterinary Medical Association, 225 (7), 1090-2
- Elsheikha HM, Murphy AJ, Mansfield LS, Viability of Sarcocystis Neurona Sporocysts After Long-term Storage., Veterinary Parasitology, 123(3-4), 257-64, Sep 2004
- Elsheikha HM, Murphy AJ, Mansfield LS, Prevalence of Sarcocystis Species Sporocysts in Northern Virginia Opossums (Didelphis Virginiana)., Parasitology Research, 93(5), 427-31, Aug 2004
- Elsheikha HM, Mansfield LS, Determination of the Activity of Sulfadiazine Against Besnoitia Darlingi Tachyzoites in Cultured Cells., Parasitology Research, 93(5), 423-6, Aug 2004
- Elsheikha HM, Mansfield LS, Assessment of Sarcocystis Neurona Sporocyst Viability and Differentiation Between Viable and Nonviable Sporocysts Using Propidium Iodide Stain., The Journal of Parasitology, 90(4), 872-5, Aug 2004
- Elsheikha HM, Mansfield LS (Aug 2004) Assessment of Sarcocystis neurona sporocyst viability and differentiation
between viable and nonviable sporocysts using propidium iodide
stain., The Journal of Parasitology, 90 (4), 872-5
- Elsheikha HM, Mansfield LS (Aug 2004) Determination of the activity of sulfadiazine against Besnoitia darlingi
tachyzoites in cultured cells., Parasitology Research, 93 (5), 423-6
- Elsheikha HM, Murphy AJ, Mansfield LS (Aug 2004) Prevalence of Sarcocystis species sporocysts in Northern Virginia opossums
(Didelphis virginiana)., Parasitology Research, 93 (5), 427-31
- Elsheikha HM, Fitzgerald SD, Rosenthal BM, Mansfield LS, Concurrent Presence of Sarcocystis Neurona Sporocysts, Besnoitia Darlingi Tissue Cysts, and Sarcocystis Inghami Sarcocysts in Naturally Infected Opossums (Didelphis Virginiana)., Journal of Veterinary Diagnostic Investigation : Official Publication of the American Association of Veterinary Laboratory Diagnosticians, Inc., 16(4), 352-6, Jul 2004
- Young VB, Knox KA, Pratt JS, Cortez JS, Mansfield LS, Rogers AB, Fox JG, Schauer DB, In Vitro and in Vivo Characterization of Helicobacter Hepaticus Cytolethal Distending Toxin Mutants., Infection and Immunity, 72(5), 2521-7, May 2004
- Rossano MG, Kaneene JB, Marteniuk JV, Banks BD, Schott HC, Mansfield LS, A Herd-level Analysis of Risk Factors for Antibodies to Sarcocystis Neurona in Michigan Equids, Preventive Veterinary Medicine, 57(1-2), 7-13, 15 Feb 2003
- Wilson DL, Bell JA, Young VB, Wilder SR, Mansfield LS, and Linz JE., Genetic Exchange By Natural Transformation Between Isogenic Campylobacter Jejuni Populations in Liquid Shake Culture, Microbiology, 149, 1-13, 2003
- Elsheikha HM, Saeed MA, Fitzgerald SD, Murphy AJ, and Mansfield LS., Effects of temperature and host cell type on the in vitro growth and development of Sarcocystis falcatula, Parasitology Research, 91(1), 22-26, 2003
- Elsheikha HM, Mansfield LS, Fitzgerald SD, and Saeed MA., Prevalence and tissue distribution of Besnoitia darlingi cysts in the Virginia opossum (Didelphis virginiana) in Michigan, Veterinary Parasitology, 115(4), 321-327, 2003
- Elsheikha HM, Fitzgerald SD, Mansfield LS, and Saeed MA, Sarcocystis inghami n. sp. (Sporozoa: Sarcocystidae) from the skeletal muscles of the Virginia opossum Didelphis virginiana in Michigan, Systematic Parasitology, 56(1), 77-84, 2003
- Elsheikha HM, Murphy AJ, Fitzgerald SD, Mansfield LS, Massey JP, and Saeed MA, Purification of Sarcocystis neurona sporocysts from opossum (Didelphis virginiana) using potassium bromide discontinuous density gradient centrifugation, Parasitology Research, 90(2), 104-109, 2003
- Rossano MG, Kaneene JB, Schott HC, Sheline KD and Mansfield LS, Assessing the agreement of Western blot test results for paired serum and cerebrospinal fluid samples from horses tested for antibodies to Sarcocystis neurona, Veterinary Parasitology 115(3): 233-238, 115(3), 233-238, 2003
- Grosjean N, Vrable RA, Murphy AJ, and Mansfield LS, Cross sectional study of Leishmania donovani: a screening of clinical canine samples, . Journal of the American Veterinary Medical Association 222(5): 603-606, 222(5), 603-606, 2003
- Mansfield LS, Gauthier DT, Abner SR, Jones KM, Wilder SR, and Urban JF, Enhancement of Disease and Pathology By Synergy of Trichuris Suis and Campylobacter Jejuni in the Colon of Immunologically Naïve Swine, American Journal of Tropical Medicine and Hygiene, 68(1), 70-80, January 2003
- Abner SR, Hill DE, Turner JR, Black ED, Bartlett P, Urban JF, and Mansfield LS, Response of intestinal epithelial cells to Trichuris suis excretory-secretory products and the influence on Campylobacter jejuni invasion under in vitro conditions, Journal of Parasitology, 88(4), 738-745, 2002
- Rossano MG, Lewis S, Owens N, Murphy AJ, and Mansfield LS, Cross-sectional study of serum antibodies to Sarcocystis neurona in cats tested for antibodies to Toxoplasma gondii, Journal of the American Veterinary Medical Association, 221(4), 511-514, 2002
- Mansfield LS, H.C. Schott II, A.J. Murphy, M.G. Rossano, S.M. Tanhauser, J.S. Patterson, K. Nelson, S.L. Ewart, J.V. Marteniuk and D.D. Bowman, and J.B. Kaneene, Comparison of Sarcocystis neurona isolates derived from horse neural tissue. Invited EPM issue of Veterinary Parasitology, Invited EPM issue of Veterinary Parasitology, 95(2001), 167-179, 2001
- Rossano MG, Kaneene JB, Marteniuk JV, Banks BD, and Mansfield LS, The seroprevalence of antibodies to Sarcocystis neurona in Michigan equids; an individual-animal-level analysis, Journal of Veterinary Preventive Medicine, 48(2001), 113-128, 2001
- Abner SR, Hill DE, Urban JF, and Mansfield LS, Trichuris suis excretory-secretory products inhibit the growth of Campylobacter jejuni, Experimental Parasitology, 99(1), 26-36, 2001
- Kruttlin E, Vrable R, Murphy AJ, Rossano MG, Mehler S, and Mansfield LS, The effects of pyrantel tartrate on Sarcocystis neurona merozoite viability, Veterinary Therapeutics, 2(3), 268-276, 2001
- Williams SM, Fulton RM, Render JA, Mansfield LS, and Bouldin M, Ocular and Encephalic Toxoplasmosis in Canaries, Avian Diseases, 45(1), 262-267, 2001
- Rossano MG, Kaneene JB, Marteniuk JV, Banks BD, and Mansfield LS, The Seroprevalence of Antibodies to Sarcocystis Neurona in Michigan Equids; An Individual-animal-level Analysis, Journal of Veterinary Preventive Medicine, 48(2001), 113-128, 2001
- Mansfield, LS and Abner S. R. Abner, Molecular Mechanisms Governing Campylobacter Pathogenicity, In: Microbial Foodborne Diseases: Mechanisms of Pathogenesis and Toxin Synthesis, Jeff Carey and John Linz eds. USDA, Washington D.C., pp. 191-243, 2000
- Mansfield LS, Gause WC, Finkelman FD, and Urban JF, Gastrointestinal Nematodes and the Immune System, In: Effects of microbes on the immune system, Lippincott-Williams and Wilkins, Philadelphia, Pennsylvania, USA, pp. 555-567, 2000
- Wilson DL, Abner SR, Newman T, Mansfield LS, and Linz JE, Identification of ciprofloxacin resistant Campylobacter jejuni by means of a fluorogenic TaqMan assay, Journal of Clinical Microbiology, 38(11), 3971-3978, 2000
- Rossano MG, Mansfield LS, Kaneene JB, Murphy AJ, Brown C, Fox CJ., Improvement of western blot test specificity for detecting equine serum antibodies to Sarcocystis neurona, Journal of Veterinary Diagnostic Investigation, 12, 28-32, 2000
- Hermesmeyer M, Limberg-Child RK, Murphy AJ, and Mansfield LS., Prevalence of Dirofilaria immitis infection among shelter cats, Journal of the American Veterinary Medical Association, 217(2), 211-212, 2000
- Urban JF, Jr., Mansfield LS, Shea-Donohue T, Gause W, Finkelman FD., Mechanisms of intestinal immunity to nematode parasites and the consequences to invasion by opportunistic bacteria, . Old Herborn University Seminar Monograph 11: Immunomodulation of the gastrointestinal mucosa (P.J. Heidt, J.C. Cebra, V.D. Rusch, D Vander Waaij, and R.I. Walker Eds.) Herborn Litterae., 1999
- Murphy AJ, and Mansfield LS, Simplified technique for isolation, excystation, and culture of Sarcocystis spp. from opossums, Journal of Parasitology, 85(5), 979-981, 1999
- Gauthier, DT and Mansfield LS., Western immunoblot analysis for distinguishing vaccination and infection status with Borrelia burgdorferi (Lyme Disease) in dogs, Journal of Veterinary Diagnostic Investigation, 11, 259-265, 1999
- Mansfield LS, Urban JF, Holley-Shanks RR, Murtaugh MP, Zarlenga DS, Foss D, Canals A, Gause W, Lunney JK, Construction of internal cDNA competitors for measuring IL-10 and IL-12 cytokine gene expression in swine., Veterinary Immunology and Immunopathology, 65(1), 63-74, 16 Sep 1998
- Bredal, WP, Gjerde BK, Eberhard ML, Aleksandersen M, Wilhelmsen and Mansfield LS., Adult Dirofilaria repens in a subcutaneous granuloma on the chest of a dog, Journal of Small Animal Practice, 39, 595-597, 1998
- Pham TS, Mansfield LS and Turiansky, G.W., Zoonoses in HIV-infected patients: risk factors and prevention, part II. Gastrointestinal, skin and other diseases, AIDS Reader, 16-21, 31 Jan 1997
- Mansfield LS, Hill DE and Urban JF., Lymphoglandular complexes process antigen in the distal colon in swine, In: Cytokines, cholera, and the gut, IOS Press: Keusch GT, and Kawakami M. eds. Boston, Mass, pp. 185-195, 1997
- Urban JF Jr, Fayer R, Sullivan C, Goldhill J, Shea-Donohue T, Madden K, Morris SC, Katona I, Gause W, Ruff M, Mansfield LS, Finkelman FD, Local TH1 and TH2 responses to parasitic infection in the intestine: regulation by IFN-gamma and IL-4, Veterinary Immunology and Immunopathology, 54(1-4), 337-44, November 1996
- Pham TS, Mansfield LS and Turiansky, G.W., Zoonoses in HIV-infected patients: risk factors and prevention, part I. nervous system and pulmonary diseases, AIDS Reader, 7-15, June 1996
- Gamble HR, Mansfield LS, Characterization of excretory-secretory products from larval stages of Haemonchus contortus cultured in vitro, Veterinary Parasitology, 62(3-4), 291-305, April 1996
- Gamble HR, Fetterer RH, Mansfield LS, Developmentally regulated zinc metalloproteinases from third- and fourth-stage larvae of the ovine nematode Haemonchus contortus, Journal of Parasitology, 82(2), 197-202, April 1996
- Mansfield LS, Urban JF Jr, The Pathogenesis of Necrotic Proliferative Colitis in Swine Is Linked to Whipworm Induced Suppression of Mucosal Immunity to Resident Bacteria, Veterinary Immunology and Immunopathology, 50(1-2), 1-17, March 1996
- Mansfield LS, Gamble HR, Alveolar mastocytosis and eosinophilia in lambs with naturally acquired
nematode infections of Protostrongylus rufescens and Haemonchus
contortus, Veterinary Immunology and Immunopathology, 49(3), 251-62, December 1995
- Mansfield LS, Alavi A, Wortman JA, Schad GA, Gamma Camera Scintigraphy for Direct Visualization of Larval Migration in Strongyloides Stercoralis-infected Dogs, The American Journal of Tropical Medicine and Hygiene, 52(3), 236-40, March 1995
- Moisan PG, Mansfield LS, Murphy AJ, and Hale A., Incidental Subcutaneous Gordiid Parasitism in a Cat, Journal of Veterinary Diagnostic Laboratory Investigation, 8, 270-272, 1995
- Mansfield LS and Schad GA., Lack of Transmammary Transmission of Strongyloides Stercoralis From a Previously Hyperinfected Bitch to Her Pups, Journal of the Helminthological Society of Washington, 62(1), 80-83, 1994
- Mansfield LS, Gamble HR, Baker JS, Lichtenfels JR, Lungworm Infection in a Sheep Flock in Maryland, Journal of the American Veterinary Medical Association, 202(4), 601-6, February 1993
- Mansfield LS, Schad GA, Strongyloides Stercoralis Infection in IgA-deficient Dogs, The American Journal of Tropical Medicine and Hygiene, 47(6), 830-6, December 1992
- Mansfield LS, Gamble HR, Fetterer RH, Characterization of the Eggshell of Haemonchus Contortus--I. Structural Components, Comparative Biochemistry and Physiology. B, Comparative Biochemistry, 103(3), 681-6, November 1992
- Mansfield LS, Schad GA, Ivermectin Treatment of Naturally Acquired and Experimentally Induced Strongyloides Stercoralis Infections in Dogs, Journal of the American Veterinary Medical Association, 201(5), 726-30, September 1992
- Gamble HR and Mansfield LS., A Simple Method for the Purification of Trichostrongyle Egg Shells, Journal of the Helminthological Society of Washington, 59(2), 234-236, 1992
- Mansfield Aikens L and Schad GA., Radiolabeling of Infective Third-stage Larvae of Strongyloides Stercoralis By Feeding [75Se]Selenomethionine-labeled Escherichia Coli to First and Second-stage Larvae, Journal of Parasitology, 75(5), 735-739, 1989
- Schad GA, Mansfield Aikens L and Smith G., Strongyloides Stercoralis: Is There a Canonical Migratory Route Through the Host?, Journal of Parasitology, 75(5), 740-749, 1989
- Nolan TJ, Mansfield Aikens L, Schad GA., Cryopreservation of First-stage and Infective Third-stage Larvae of Strongyloides Stercoralis, Journal of Parasitology, 74, 387-391, 1988
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