Publications by authors named "Lois Zitzow"

13 Publications

  • Page 1 of 1

Applied Institutional Approaches for the Evaluation and Management of Zoonoses in Contemporary Laboratory Animal Research Facilities.

ILAR J 2018 12;59(2):134-143

Department of Population Health, University of Georgia College of Veterinary Medicine, Athens, Georgia.

Zoonoses, diseases transmitted between animals and humans, have been a concern in laboratory animal medicine for decades. Exposure to zoonotic organisms not only poses health risks to personnel and research animals but may also affect research integrity. Early laboratory animal programs were ineffective at excluding and preventing transmission of zoonotic diseases: the health status of the animals were often unknown, endemic diseases occurred frequently, housing conditions were less controlled, and veterinary care programs were decentralized. Over time, these conditions improved, but despite this, zoonotic diseases remain a contemporary concern. To reduce the incidence of zoonoses, management should perform an accurate risk assessment that takes into account the type of research performed, animal species used, animal sources, and housing conditions. Specific research practices, such as the use of biological materials, can also affect the risk assessment and should be considered. Once identified, the characteristics of significant zoonotic organisms can be examined. In addition, personnel attitudes and training, facility design and management, equipment availability, personal protective equipment used, standard operating procedures, and the institution's vermin control program can impact the risk assessment. The effectiveness of the occupational health and safety program at managing risks of zoonoses should also be examined. Risk assessment, in the context of zoonotic disease prevention, is a complex exercise and is most effective when a team approach is used and includes research, husbandry, veterinary, and biosafety personnel.
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http://dx.doi.org/10.1093/ilar/ily016DOI Listing
December 2018

Redirecting the request to the IACUC.

Lab Anim (NY) 2018 06;47(6):140-141

University of Georgia, Athens, Georgia, USA.

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http://dx.doi.org/10.1038/s41684-018-0071-2DOI Listing
June 2018

Intranasally administered IGF-1 inhibits spreading depression in vivo.

Brain Res 2017 Dec 23;1677:47-57. Epub 2017 Sep 23.

Department of Neurology, The University of Chicago Medical Center, 5841 South Maryland Avenue, Chicago, IL 60637-1470, United States. Electronic address:

Spreading depression (SD) is a wave of cellular depolarization that travels slowly through susceptible gray matter brain areas. SD is the most likely cause of migraine aura and perhaps migraine pain, and is a well-accepted animal model of migraine. Identification of therapeutics that can prevent SD may have clinical relevance toward migraine treatment. Here we show that insulin-like growth factor-1 (IGF-1) significantly inhibited neocortical SD in vivo after intranasal delivery to rats. A single dose of IGF-1 inhibited SD within an hour, and continued to protect for at least seven days thereafter. A two-week course of IGF-1, administered every third day, further decreased SD susceptibility and showed no aberrant effects on glial activation, nasal mucosa, or serum markers of toxicity. SD begets SD in vitro by mechanisms that involve microglial activation. We add to this relationship by showing that recurrent SD in vivo increased susceptibility to subsequent SD, and that intervention with IGF-1 significantly interrupted this pathology. These findings support nasal administration of IGF-1 as a novel intervention capable of mitigating SD susceptibility, and as a result, potentially migraine.
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http://dx.doi.org/10.1016/j.brainres.2017.09.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5993215PMC
December 2017

Considerations for Infectious Disease Research Studies Using Animals.

Comp Med 2017 Jun;67(3):222-231

University Research Animal Resources, Office of Research, University of Georgia, Athens, Georgia;, Email:

Animal models are vital in understanding the transmission and pathogenesis of infectious organisms and the host immune response to infection. In addition, animal models are essential in vaccine and therapeutic drug development and testing. Prior to selecting an animal model to use when studying an infectious agent, the scientific team must determine that sufficient in vitro and ex vivo data are available to justify performing research in an animal model, that ethical considerations are addressed, and that the data generated from animal work will add useful information to the body of scientific knowledge. Once it is established that an animal should be used, the questions become 'Which animal model is most suitable?' and 'Which experimental design issues should be considered?' The answers to these questions take into account numerous factors, including scientific, practical, welfare, and regulatory considerations, which are the focus of this article.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482514PMC
June 2017

Reconsider, communicate, collaborate.

Lab Anim (NY) 2014 Nov;43(11):391-2

Animal Resources Center, and Associate Professor, Department of Surgery at The University of Chicago, Chicago, IL.

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http://dx.doi.org/10.1038/laban.643DOI Listing
November 2014

Transgenic neuronal overexpression reveals that stringently regulated p23 expression is critical for coordinated movement in mice.

Mol Neurodegener 2011 Dec 28;6:87. Epub 2011 Dec 28.

Departments of Neurobiology, Neurology, and Pathology, The University of Chicago, Chicago, IL 60637, USA.

Background: p23 belongs to the highly conserved p24 family of type I transmembrane proteins, which participate in the bidirectional protein transport between the endoplasmic reticulum and Golgi apparatus. Mammalian p23 has been shown to interact with γ-secretase complex, and modulate secretory trafficking as well as intramembranous processing of amyloid precursor protein in cultured cells. Negative modulation of β-amyloid production by p23 in cultured cell lines suggested that elevation of p23 expression in neurons might mitigate cerebral amyloid burden.

Results: We generated several lines of transgenic mice expressing human p23 in neurons under the control of Thy-1.2 promoter. We found that even a 50% increase in p23 levels in the central nervous system of mice causes post-natal growth retardation, severe neurological problems characterized by tremors, seizure, ataxia, and uncoordinated movements, and premature death. The severity of the phenotype closely correlated with the level of p23 overexpression in multiple transgenic lines. While the number and general morphology of neurons in Hup23 mice appeared to be normal throughout the brain, abnormal non-Golgi p23 localization was observed in a subset of neurons with high transgene expression in brainstem. Moreover, detailed immunofluorescence analysis revealed marked proliferation of astrocytes, activation of microglia, and thinning of myelinated bundles in brainstem of Hup23 mice.

Conclusions: These results demonstrate that proper level of p23 expression is critical for neuronal function, and perturbing p23 function by overexpression initiates a cascade of cellular reactions in brainstem that leads to severe motor deficits and other neurological problems, which culminate in premature death. The neurological phenotype observed in Hup23 mice highlights significant adverse effects associated with manipulating neuronal expression of p23, a previously described negative modulator of γ-secretase activity and β-amyloid production. Moreover, our report has broader relevance to molecular mechanisms in several neurodegenerative diseases as it highlights the inherent vulnerability of the early secretory pathway mechanisms that ensure proteostasis in neurons.
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http://dx.doi.org/10.1186/1750-1326-6-87DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3259059PMC
December 2011

Removal of lactate dehydrogenase-elevating virus from human-in-mouse breast tumor xenografts by cell-sorting.

J Virol Methods 2011 May 24;173(2):266-70. Epub 2011 Feb 24.

The Ben May Department for Cancer Research, The University of Chicago, Chicago, IL 60637, USA.

Lactate dehydrogenase-elevating virus (LDV) can infect transplantable mouse tumors or xenograft tumors in mice through LDV-contaminated mouse biological materials, such as Matrigel, or through mice infected with LDV. LDV infects specifically mouse macrophages and alters immune system and tumor phenotype. The traditional approaches to remove LDV from tumor cells, by transplanting tumors into rats or culturing tumor cells in vitro, are inefficient, labor-intensive and time-consuming. Furthermore, these approaches are not feasible for primary tumor cells that cannot survive tissue culture conditions or that may change phenotype in rats. This study reports that fluorescence-activated cell sorting (FACS) is a simple and efficient approach for purifying living primary human breast tumor cells from LDV(+) mouse stromal cells, which can be completed in a few hours. When purified from Matrigel contaminated LDV(+) tumors, sorted human breast tumor cells, as well as tumors grown from sorted cells, were shown to be LDV-free, as tested by PCR. The results demonstrate that cell sorting is effective, much faster and less likely to alter tumor cell phenotype than traditional methods for removing LDV from xenograft models. This approach may also be used to remove other rodent-specific viruses from models derived from distinct tissues or species with sortable markers, where virus does not replicate in the cells to be purified.
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http://dx.doi.org/10.1016/j.jviromet.2011.02.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3086718PMC
May 2011

Severe acute respiratory syndrome vaccine efficacy in ferrets: whole killed virus and adenovirus-vectored vaccines.

J Gen Virol 2008 Sep;89(Pt 9):2136-2146

Brody School of Medicine, Department of Microbiology and Immunology, East Carolina University, Greenville, NC 27834, USA.

Although the 2003 severe acute respiratory syndrome (SARS) outbreak was controlled, repeated transmission of SARS coronavirus (CoV) over several years makes the development of a SARS vaccine desirable. We performed a comparative evaluation of two SARS vaccines for their ability to protect against live SARS-CoV intranasal challenge in ferrets. Both the whole killed SARS-CoV vaccine (with and without alum) and adenovirus-based vectors encoding the nucleocapsid (N) and spike (S) protein induced neutralizing antibody responses and reduced viral replication and shedding in the upper respiratory tract and progression of virus to the lower respiratory tract. The vaccines also diminished haemorrhage in the thymus and reduced the severity and extent of pneumonia and damage to lung epithelium. However, despite high neutralizing antibody titres, protection was incomplete for all vaccine preparations and administration routes. Our data suggest that a combination of vaccine strategies may be required for effective protection from this pathogen. The ferret may be a good model for SARS-CoV infection because it is the only model that replicates the fever seen in human patients, as well as replicating other SARS disease features including infection by the respiratory route, clinical signs, viral replication in upper and lower respiratory tract and lung damage.
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http://dx.doi.org/10.1099/vir.0.2008/001891-0DOI Listing
September 2008

Adenovirus-based vaccine prevents pneumonia in ferrets challenged with the SARS coronavirus and stimulates robust immune responses in macaques.

Vaccine 2007 Jul 7;25(28):5220-31. Epub 2007 May 7.

Special Pathogens Program, National Microbiology Laboratory, Health Canada, Canadian Science Centre for Human and Animal Health, Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada.

A ferret model of severe acute respiratory syndrome (SARS)-CoV infection was used to evaluate the efficacy of an adenovirus vaccine. Animals were subjected to heterologous prime-boost using vectors from human serotype 5 and chimpanzee derived adenoviruses (human AdHu5 and chimpanzee AdC7) expressing spike protein followed by intranasal challenge with SARS-CoV. Vaccination led to a substantial reduction in viral load and prevented the severe pneumonia seen in unvaccinated animals. The same prime-boost strategy was effective in rhesus macaques in eliciting SARS-CoV specific immune responses. These data indicate that a heterologous adenovirus-based prime-boost vaccine strategy could safely stimulate strong immunity that may be needed for complete protection against SARS-CoV infection.
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http://dx.doi.org/10.1016/j.vaccine.2007.04.065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115643PMC
July 2007

Comparative evaluation of two severe acute respiratory syndrome (SARS) vaccine candidates in mice challenged with SARS coronavirus.

J Gen Virol 2006 Mar;87(Pt 3):641-650

Michael Smith Laboratories and Departments of Biochemistry and Molecular Biology and Microbiology and Immunology, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.

Two different severe acute respiratory syndrome (SARS) vaccine strategies were evaluated for their ability to protect against live SARS coronavirus (CoV) challenge in a murine model of infection. A whole killed (inactivated by beta-propiolactone) SARS-CoV vaccine and a combination of two adenovirus-based vectors, one expressing the nucleocapsid (N) and the other expressing the spike (S) protein (collectively designated Ad S/N), were evaluated for the induction of serum neutralizing antibodies and cellular immune responses and their ability to protect against pulmonary SARS-CoV replication. The whole killed virus (WKV) vaccine given subcutaneously to 129S6/SvEv mice was more effective than the Ad S/N vaccine administered either intranasally or intramuscularly in inhibiting SARS-CoV replication in the murine respiratory tract. This protective ability of the WKV vaccine correlated with the induction of high serum neutralizing-antibody titres, but not with cellular immune responses as measured by gamma interferon secretion by mouse splenocytes. Titres of serum neutralizing antibodies induced by the Ad S/N vaccine administered intranasally or intramuscularly were significantly lower than those induced by the WKV vaccine. However, Ad S/N administered intranasally, but not intramuscularly, significantly limited SARS-CoV replication in the lungs. Among the vaccine groups, SARS-CoV-specific IgA was found only in the sera of mice immunized intranasally with Ad S/N, suggesting that mucosal immunity may play a role in protection for the intranasal Ad S/N delivery system. Finally, the sera of vaccinated mice contained antibodies to S, further suggesting a role for this protein in conferring protective immunity against SARS-CoV infection.
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http://dx.doi.org/10.1099/vir.0.81579-0DOI Listing
March 2006

Cross-fostering in combination with ivermectin therapy: a method to eradicate murine fur mites.

Contemp Top Lab Anim Sci 2005 Jul;44(4):12-6

Division of Animal Resources, Whitehead Biomedical Research Building, Suite G02, 615 Michael Street, Emory University, Atlanta, Georgia 30322, USA.

A colony of mutant mice with sickle cell anemia was infested with the fur mites Myocoptes musculinus and Myobia musculi. Pups of sickle-cell phenotype obtained by cesarean section prior to natural birth were of such poor vigor that none survived the combined insults of delivery by hysterectomy and cross-fostering. Consequently, surgical rederivation, the most reliable means of mite eradication, was not an option. Because furless mice are not susceptible to mite infestation and because neonates putatively remain free of mites until 4 to 5 days after birth, pups born by natural delivery were cross-fostered within 0 to 36 h to outbred lactating females treated once with ivermectin (2 mg/kg topically) at the time of transfer and housed in filter-top cages. Cross-fostering in conjunction with topical ivermectin administered to weaned mice one or more times at approximate 9-day intervals beginning on the day of weaning was successful in reliably eradicating mites. In addition, the 58% postnatal survivability of pups cross-fostered to dams given ivermectin was equivalent to that of natural-born pups that were reared by their untreated biological mothers.
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July 2005

Pathogenesis of avian influenza A (H5N1) viruses in ferrets.

J Virol 2002 May;76(9):4420-9

Influenza Branch, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.

Highly pathogenic avian influenza A H5N1 viruses caused outbreaks of disease in domestic poultry and humans in Hong Kong in 1997. Direct transmission of the H5N1 viruses from birds to humans resulted in 18 documented cases of respiratory illness, including six deaths. Here we evaluated two of the avian H5N1 viruses isolated from humans for their ability to replicate and cause disease in outbred ferrets. A/Hong Kong/483/97 virus was isolated from a fatal case and was highly pathogenic in the BALB/c mouse model, whereas A/Hong Kong/486/97 virus was isolated from a case with mild illness and exhibited a low-pathogenicity phenotype in mice. Ferrets infected intranasally with 10(7) 50% egg infectious doses (EID(50)) of either H5N1 virus exhibited severe lethargy, fever, weight loss, transient lymphopenia, and replication in the upper and lower respiratory tract, as well as multiple systemic organs, including the brain. Gastrointestinal symptoms were seen in some animals. In contrast, weight loss and severe lethargy were not noted in ferrets infected with 10(7) EID(50) of two recent human H3N2 viruses, although these viruses were also isolated from the brains, but not other extrapulmonary organs, of infected animals. The results demonstrate that both H5N1 viruses were highly virulent in the outbred ferret model, unlike the differential pathogenicity documented in inbred BALB/c mice. We propose the ferret as an alternative model system for the study of these highly pathogenic avian viruses.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC155091PMC
http://dx.doi.org/10.1128/jvi.76.9.4420-4429.2002DOI Listing
May 2002

Identification of an endocrine disrupting agent from corn with mitogenic activity.

Biochem Biophys Res Commun 2002 Mar;291(3):692-700

Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.

A mitogenic agent in corncob bedding and fresh corn products disrupts sexual behavior and estrous cyclicity in rats. The mitogenic activity resides in an isomeric mixture of linoleic acid derivatives with a tetrahydrofuran ring and two hydroxyl groups (THF-diols) that include 9, (12)-oxy-10,13-dihydroxystearic acid and 10, (13)-oxy-9,12-dihydroxystearic acid. Synthetic THF-diols stimulated breast cancer cell proliferation in vitro and disrupted the estrous cycle in female rats at oral doses of approximately 0.30 mg/kg body weight/day. Exposure to THF-diols may disrupt endocrine function in experimental animals at doses approximately 200 times lower than classical phytoestrogens, promote proliferation of breast or prostate cancer, and adversely affect human health.
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http://dx.doi.org/10.1006/bbrc.2002.6499DOI Listing
March 2002