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Article ; Online: The association among insomnia symptom severity, comorbid symptoms, and suicidal ideation in two veteran cohorts meeting diagnostic criteria for insomnia disorder.

Kramer, Emily B / Gaeddert, Laurel A / Jackson, Christine L / Hostetter, Trisha A / Forster, Jeri E / Nazem, Sarra

2023 Volume 79, Issue 5, Page(s) 1420–1433

Abstract: Objective: Examine the association between insomnia symptom severity and suicidal ideation (SI), after adjusting for clinical comorbidity in veterans meeting diagnostic criteria for insomnia disorder.: Methods: Secondary data analyses of ... ...

Abstract	Objective: Examine the association between insomnia symptom severity and suicidal ideation (SI), after adjusting for clinical comorbidity in veterans meeting diagnostic criteria for insomnia disorder. Methods: Secondary data analyses of psychometrically validated baseline assessments of depression, posttraumatic stress disorder (PTSD), and anxiety symptoms from two online insomnia intervention randomized clinical trials (n = 232; n = 80) were conducted. Multiple linear regression was used to determine the association between insomnia symptom severity and SI, after controlling for clinical comorbidity and demographics. Results: Insomnia symptom severity was significantly correlated with comorbid depression, PTSD, and anxiety symptoms in both cohorts and significantly correlated with SI in one. After controlling for demographics and clinical comorbidity, insomnia symptom severity was not significantly associated with SI in linear regression models. Conclusion: Findings extend insomnia-suicide research by providing evidence that insomnia symptom severity may not confer a unique risk for SI above comorbid mental health symptoms in veterans meeting diagnostic criteria for insomnia disorder.
MeSH term(s)	Humans ; Comorbidity ; Military Personnel/psychology ; Sleep Initiation and Maintenance Disorders/epidemiology ; Stress Disorders, Post-Traumatic/psychology ; Suicidal Ideation ; Veterans/psychology
Language	English
Publishing date	2023-01-25
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	219160-x
ISSN	1097-4679 ; 0021-9762
ISSN (online)	1097-4679
ISSN	0021-9762
DOI	10.1002/jclp.23488
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Article ; Online: Patient-Perceived Satisfaction and Knowledge Uptake in a Combined Cardio-Obstetrics Clinic.

Florio, Karen L / White, Darcy / Gosch, Kensey / Patel, Neil / Daming, Tara / Williams, Emily M / Hostetter, Sarah / Gray, Rebecca / Nelson, Lynne / Swearingen, Kathleen / Henricks, Christine / Grodzinsky, Anna / Rader, Valerie / Lee, John / Magalski, Anthony / Schmidt, Laura

Journal of cardiovascular development and disease

2022 Volume 9, Issue 12

Abstract: Heart disease is the leading cause of pregnancy-related mortality in the United States and has led to the development of combined cardio-obstetrics (COB) clinics as a model for prenatal care. In other areas of medicine, these types of collaborative care ... ...

Abstract	Heart disease is the leading cause of pregnancy-related mortality in the United States and has led to the development of combined cardio-obstetrics (COB) clinics as a model for prenatal care. In other areas of medicine, these types of collaborative care models have shown improvement in morbidity, mortality, and patient satisfaction. There is some data to suggest that a combined COB clinic improves maternal outcomes but there is no data to suggest patients prefer this type of care model. This study aims to evaluate patient satisfaction in a combined COB clinic and whether this type of model enhances perceived communication and knowledge uptake. A quality questionnaire was developed to assess patient perceptions regarding communication, satisfaction, and perceived knowledge. Patients who attended the clinic (
Language	English
Publishing date	2022-12-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2777082-5
ISSN	2308-3425 ; 2308-3425
ISSN (online)	2308-3425
ISSN	2308-3425
DOI	10.3390/jcdd9120433
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Article ; Online: Timing is everything: order of administration of 5-aza 2' deoxycytidine, trichostatin A and tamoxifen changes estrogen receptor mRNA expression and cell sensitivity.

Hostetter, Christine L / Licata, Lauren A / Keen, Judith Clancy

Cancer letters

2009 Volume 275, Issue 2, Page(s) 178–184

Abstract: Restoration of estrogen receptor (ER) expression using epigenetic inhibitors re-establishes expression of the estrogen receptor (ER) and restores tamoxifen sensitivity in ER negative breast cancer cells. We tested if order of administration of the DNMT ( ... ...

Abstract	Restoration of estrogen receptor (ER) expression using epigenetic inhibitors re-establishes expression of the estrogen receptor (ER) and restores tamoxifen sensitivity in ER negative breast cancer cells. We tested if order of administration of the DNMT (5-aza 2' deoxycytidine/AZA) or HDAC (trichostatin A/TSA) inhibitors and tamoxifen affected ER re-expression and tamoxifen sensitivity. Treatment with AZA followed by co-administration of TSA plus tamoxifen resulted in the greatest ER re-expression and tamoxifen sensitivity, although sensitivity was not increased as robustly as expected. This could be due to increased cytoplasmic levels of HuR, suggesting that cytoplasmic HuR levels are central to tamoxifen responsiveness.
MeSH term(s)	Azacitidine/administration & dosage ; Azacitidine/analogs & derivatives ; Azacitidine/pharmacology ; Cell Line, Tumor ; Drug Administration Schedule ; Estrogen Receptor Modulators/administration & dosage ; Estrogen Receptor Modulators/pharmacology ; Humans ; Hydroxamic Acids/administration & dosage ; Hydroxamic Acids/pharmacology ; RNA, Messenger/genetics ; Receptors, Estrogen/genetics ; Tamoxifen/administration & dosage ; Tamoxifen/pharmacology
Chemical Substances	Estrogen Receptor Modulators ; Hydroxamic Acids ; RNA, Messenger ; Receptors, Estrogen ; Tamoxifen (094ZI81Y45) ; trichostatin A (3X2S926L3Z) ; decitabine (776B62CQ27) ; Azacitidine (M801H13NRU)
Language	English
Publishing date	2009-03-18
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	195674-7
ISSN	1872-7980 ; 0304-3835
ISSN (online)	1872-7980
ISSN	0304-3835
DOI	10.1016/j.canlet.2008.10.005
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Article ; Online: The RNA-binding protein HuR regulates GATA3 mRNA stability in human breast cancer cell lines.

Licata, Lauren A / Hostetter, Christine L / Crismale, James / Sheth, Anjali / Keen, Judith Clancy

Breast cancer research and treatment

2009 Volume 122, Issue 1, Page(s) 55–63

Abstract: Meta-analyses of microarray data indicate that GATA3 is co-expressed with estrogen receptor alpha (ER) in breast cancer cells. While the significance of this remains unclear, it is thought that GATA3 may serve as a prognostic indicator in breast tumors ... ...

Abstract	Meta-analyses of microarray data indicate that GATA3 is co-expressed with estrogen receptor alpha (ER) in breast cancer cells. While the significance of this remains unclear, it is thought that GATA3 may serve as a prognostic indicator in breast tumors and may play a role in ER signaling. Recently, reciprocal regulation of GATA3 and ER transcription was demonstrated, suggesting that control of their expression is intertwined. We sought to determine whether GATA3 and ER expression was also coordinately regulated at other levels. Unlike ER, GATA3 was not under epigenetic control and was not re-expressed in the presence of DNMT or HDAC inhibitors in ER/GATA3-negative cells. However, like ER, these inhibitors decreased GATA3 expression in ER/GATA3-positive cell lines. We have previously reported that ER mRNA stability is increased through binding of the RNA-binding protein HuR/ELAV1 to the 3'untranslated region (UTR) and that DNMT and HDAC inhibitors reduce ER expression by altering this interaction. Biotin pull-down assays using a biotinylated GATA3 RNA probe confirmed that HuR also binds to the GATA3 3'UTR. Inhibition of HuR using siRNA probes decreased GATA3 mRNA, mRNA stability and protein expression, indicating that HuR plays a role in regulating GATA3 expression. Inhibition of either HuR or GATA3 reduced cell growth of MCF7 cells. Based on our findings, it is clear that coordinate regulation of ER and GATA3 occurs, however differences do exist. These findings may aid in identification of new targets that control cell growth of breast cancer cells.
MeSH term(s)	3' Untranslated Regions ; Antigens, Surface/physiology ; Base Sequence ; Binding Sites ; Biotinylation ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Cell Line, Tumor/drug effects ; Cell Line, Tumor/metabolism ; Consensus Sequence ; ELAV Proteins ; ELAV-Like Protein 1 ; Epigenesis, Genetic ; Estrogen Receptor alpha/biosynthesis ; Estrogen Receptor alpha/genetics ; Female ; GATA3 Transcription Factor/biosynthesis ; GATA3 Transcription Factor/genetics ; GATA3 Transcription Factor/physiology ; Gene Expression Regulation, Neoplastic ; Histone Deacetylase Inhibitors/pharmacology ; Humans ; Molecular Sequence Data ; Protein Binding ; RNA Stability/physiology ; RNA, Messenger/metabolism ; RNA, Neoplasm/metabolism ; RNA, Small Interfering/pharmacology ; RNA-Binding Proteins/physiology
Chemical Substances	3' Untranslated Regions ; Antigens, Surface ; ELAV Proteins ; ELAV-Like Protein 1 ; ELAVL1 protein, human ; ESR1 protein, human ; Estrogen Receptor alpha ; GATA3 Transcription Factor ; GATA3 protein, human ; Histone Deacetylase Inhibitors ; RNA, Messenger ; RNA, Neoplasm ; RNA, Small Interfering ; RNA-Binding Proteins
Language	English
Publishing date	2009-09-02
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	604563-7
ISSN	1573-7217 ; 0167-6806
ISSN (online)	1573-7217
ISSN	0167-6806
DOI	10.1007/s10549-009-0517-8
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Article: Zebrafish pronephros: a model for understanding cystic kidney disease.

Hostetter, Christine L / Sullivan-Brown, Jessica L / Burdine, Rebecca D

Developmental dynamics : an official publication of the American Association of Anatomists

2003 Volume 228, Issue 3, Page(s) 514–522

Abstract: The embryonic kidney of the zebrafish is the pronephros. The ease of genetic analysis and experimentation in zebrafish, coupled with the simplicity of the pronephros, make the zebrafish an ideal model system for studying kidney development and function. ... ...

Abstract	The embryonic kidney of the zebrafish is the pronephros. The ease of genetic analysis and experimentation in zebrafish, coupled with the simplicity of the pronephros, make the zebrafish an ideal model system for studying kidney development and function. Several mutations have been isolated in zebrafish genetic screens that result in cyst formation in the pronephros. Cloning and characterization of these mutations will provide insight into kidney development but may also provide understanding of the molecular basis of cystic kidney diseases. In this review, we focus on the zebrafish as a model for understanding cystic kidney disease and the links between cystic kidney disease and left-right patterning.
MeSH term(s)	Animals ; Body Patterning/physiology ; Kidney/abnormalities ; Kidney/embryology ; Kidney Diseases, Cystic ; Models, Animal ; Morphogenesis ; Zebrafish/embryology
Language	English
Publishing date	2003-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	1102541-4
ISSN	1097-0177 ; 1058-8388
ISSN (online)	1097-0177
ISSN	1058-8388
DOI	10.1002/dvdy.10371
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Article: The RNA-binding protein HuR regulates GATA3 mRNA stability in human breast cancer cell lines

Licata, Lauren A / Hostetter, Christine L / Crismale, James / Sheth, Anjali / Keen, Judith Clancy

Breast cancer research and treatment. 2010 July, v. 122, no. 1

2010

Abstract	Meta-analyses of microarray data indicate that GATA3 is co-expressed with estrogen receptor alpha (ER) in breast cancer cells. While the significance of this remains unclear, it is thought that GATA3 may serve as a prognostic indicator in breast tumors and may play a role in ER signaling. Recently, reciprocal regulation of GATA3 and ER transcription was demonstrated, suggesting that control of their expression is intertwined. We sought to determine whether GATA3 and ER expression was also coordinately regulated at other levels. Unlike ER, GATA3 was not under epigenetic control and was not re-expressed in the presence of DNMT or HDAC inhibitors in ER/GATA3-negative cells. However, like ER, these inhibitors decreased GATA3 expression in ER/GATA3-positive cell lines. We have previously reported that ER mRNA stability is increased through binding of the RNA-binding protein HuR/ELAV1 to the 3′untranslated region (UTR) and that DNMT and HDAC inhibitors reduce ER expression by altering this interaction. Biotin pull-down assays using a biotinylated GATA3 RNA probe confirmed that HuR also binds to the GATA3 3′UTR. Inhibition of HuR using siRNA probes decreased GATA3 mRNA, mRNA stability and protein expression, indicating that HuR plays a role in regulating GATA3 expression. Inhibition of either HuR or GATA3 reduced cell growth of MCF7 cells. Based on our findings, it is clear that coordinate regulation of ER and GATA3 occurs, however differences do exist. These findings may aid in identification of new targets that control cell growth of breast cancer cells.
Language	English
Dates of publication	2010-07
Size	p. 55-63.
Publisher	Springer US
Publishing place	Boston
Document type	Article
ZDB-ID	604563-7
ISSN	1573-7217 ; 0167-6806
ISSN (online)	1573-7217
ISSN	0167-6806
DOI	10.1007/s10549-009-0517-8
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Zebrafish mutations affecting cilia motility share similar cystic phenotypes and suggest a mechanism of cyst formation that differs from pkd2 morphants.

Sullivan-Brown, Jessica / Schottenfeld, Jodi / Okabe, Noriko / Hostetter, Christine L / Serluca, Fabrizio C / Thiberge, Stephan Y / Burdine, Rebecca D

Developmental biology

2008 Volume 314, Issue 2, Page(s) 261–275

Abstract: Zebrafish are an attractive model for studying the earliest cellular defects occurring during renal cyst formation because its kidney (the pronephros) is simple and genes that cause cystic kidney diseases (CKD) in humans, cause pronephric dilations in ... ...

Abstract	Zebrafish are an attractive model for studying the earliest cellular defects occurring during renal cyst formation because its kidney (the pronephros) is simple and genes that cause cystic kidney diseases (CKD) in humans, cause pronephric dilations in zebrafish. By comparing phenotypes in three different mutants, locke, swt and kurly, we find that dilations occur prior to 48 hpf in the medial tubules, a location similar to where cysts form in some mammalian diseases. We demonstrate that the first observable phenotypes associated with dilation include cilia motility and luminal remodeling defects. Importantly, we show that some phenotypes common to human CKD, such as an increased number of cells, are secondary consequences of dilation. Despite having differences in cilia motility, locke, swt and kurly share similar cystic phenotypes, suggesting that they function in a common pathway. To begin to understand the molecular mechanisms involved in cyst formation, we have cloned the swt mutation and find that it encodes a novel leucine rich repeat containing protein (LRRC50), which is thought to function in correct dynein assembly in cilia. Finally, we show that knock-down of polycystic kidney disease 2 (pkd2) specifically causes glomerular cysts and does not affect cilia motility, suggesting multiple mechanisms exist for cyst formation.
MeSH term(s)	Animals ; Cilia/physiology ; Cloning, Molecular ; Embryo, Nonmammalian/physiology ; Kidney Glomerulus/physiology ; Kidney Tubules/physiology ; Microscopy, Video ; Mutagenesis ; Mutation ; Nephrons/embryology ; Nephrons/physiology ; Nephrons/physiopathology ; Phenotype ; Zebrafish/genetics ; Zebrafish/physiology ; Zebrafish Proteins/genetics
Chemical Substances	Zebrafish Proteins
Language	English
Publishing date	2008-02-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1114-9
ISSN	1095-564X ; 0012-1606
ISSN (online)	1095-564X
ISSN	0012-1606
DOI	10.1016/j.ydbio.2007.11.025
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Article ; Online: Cytoplasmic accumulation of the RNA binding protein HuR is central to tamoxifen resistance in estrogen receptor positive breast cancer cells.

Hostetter, Christine / Licata, Lauren A / Witkiewicz, Agnieszka / Costantino, Christina L / Yeo, Charles J / Brody, Jonathan R / Keen, Judith Clancy

Cancer biology & therapy

2008 Volume 7, Issue 9, Page(s) 1496–1506

Abstract: With prolonged exposure, a majority of estrogen receptor positive cancers develop resistance to tamoxifen and subsequent therapies including selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs). While much is known about ... ...

Abstract	With prolonged exposure, a majority of estrogen receptor positive cancers develop resistance to tamoxifen and subsequent therapies including selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs). While much is known about overexpression of key growth promoting receptors including EGF, erbB2/Her2 and IGF receptors and subsequent activation of MAPK signaling associated with resistance, the underlying mechanism in the development of resistance still remains unknown. We found that inhibition of JNK, a member of the MAPK family, decreases cytoplasmic accumulation of the RNA binding protein HuR. This data combined with previous reports that erbB2/Her2 and IGF-IR signals through JNK, led us to hypothesize that cytoplasmic accumulation of HuR may be a key contributor to development of tamoxifen resistance. Therefore, we tested the effect of HuR expression on tamoxifen responsiveness in both tamoxifen sensitive MCF7 and tamoxifen resistant BT474 cell lines. We found that decreasing the cytoplasmic HuR levels in the cells increases tamoxifen responsiveness in both cell lines. Conversely, the overexpression of HuR establishes tamoxifen resistance in MCF7 cells. Therefore, our data indicate that HuR is central to tamoxifen resistance. Interestingly, we found that acute exposure (24 and 48 h) of MCF7 cells to tamoxifen increased cytoplasmic levels of HuR and concomitantly it's ligand pp32, suggesting a novel molecular mechanism of resistance and acute response to tamoxifen through increased stability of mRNA transcripts that code for drug-resistant transcripts. Indeed, evaluation of primary breast tumors revealed a correlation between tumor grade, tamoxifen responsiveness and cytoplasmic HuR status. Therefore, inhibition of the cytoplasmic accumulation of HuR concomitantly with the administration of current therapeutics may be a successful treatment strategy. Our data describe a novel mechanism for the development of tamoxifen resistance and is the first study to identify an RNA binding protein as a key mediator of resistance in breast cancer cells.
MeSH term(s)	Antigens, Surface/genetics ; Antigens, Surface/metabolism ; Antineoplastic Agents, Hormonal/pharmacology ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; Cell Line, Tumor ; Cytoplasm/metabolism ; Drug Resistance, Neoplasm/drug effects ; ELAV Proteins ; ELAV-Like Protein 1 ; Female ; Humans ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/metabolism ; Receptors, Estrogen/drug effects ; Receptors, Estrogen/genetics ; Receptors, Estrogen/metabolism ; Tamoxifen/pharmacology
Chemical Substances	Antigens, Surface ; Antineoplastic Agents, Hormonal ; ELAV Proteins ; ELAV-Like Protein 1 ; ELAVL1 protein, human ; RNA-Binding Proteins ; Receptors, Estrogen ; Tamoxifen (094ZI81Y45)
Language	English
Publishing date	2008-09-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2146305-0
ISSN	1555-8576 ; 1538-4047
ISSN (online)	1555-8576
ISSN	1538-4047
DOI	10.4161/cbt.7.9.6490
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Zs.A 5887: Show issues

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Article ; Online: Pathogen-derived oligosaccharides improve innate immune response to intracellular parasite infection.

Osanya, Alex / Song, Eun-Ho / Metz, Kyle / Shimak, Raeann M / Boggiatto, Paola Mercedes / Huffman, Elise / Johnson, Charles / Hostetter, Jesse M / Pohl, Nicola L B / Petersen, Christine A

The American journal of pathology

2011 Volume 179, Issue 3, Page(s) 1329–1337

Abstract: Pathogen glycolipids, including Leishmania spp. lipophosphoglycan (LPG) and Mycobacterium tuberculosis mannosylated lipoarabinomannan (ManLAM), modulate essential interactions with host phagocytic cells. Polysaccharide and lipid components promote ... ...

Abstract	Pathogen glycolipids, including Leishmania spp. lipophosphoglycan (LPG) and Mycobacterium tuberculosis mannosylated lipoarabinomannan (ManLAM), modulate essential interactions with host phagocytic cells. Polysaccharide and lipid components promote immunomodulation. Owing to the stereochemistry required to synthesize oligosaccharides, the roles for oligosaccharides in the pathogenesis of infectious diseases have remained largely unknown. Recent advances in carbohydrate chemistry allowed us to synthesize pathogen surface oligosaccharides to discern their immune response-altering activities. Trimannose cap carbohydrates from ManLAM and LPG altered the production of proinflammatory cytokines via a toll-like receptor (TLR2)-mediated mechanism in vitro and in vivo. In vivo treatment with trimannose led to increased Th1-polarizing, IL-12p40-producing cells from the draining lymph nodes of treated Leishmania major-infected mice compared with cells from untreated infected mice. Trimannose treatment increased the production of other Th1 proinflammatory cytokines (ie, interferon-γ, IL-6, and tumor necrosis factor-α) critical for a productive immune response to either pathogen. This significant difference in cytokine production between trimannose cap sugar-treated and control groups was not observed in draining lymph node cells from TLR2(-/-) mice. Type of inflammation and rate of bead entry into macrophages and dendritic cells were different for trimannose-coated beads compared with control oligosaccharide-coated beads, indicating selective lectin receptor/oligosaccharide interactions mediating cell entry and cytokine production. These novel findings may prompt the development of targeted oligosaccharide adjuvants against chronic infections.
MeSH term(s)	Animals ; Cell Line ; Cytokines/biosynthesis ; Enzyme-Linked Immunosorbent Assay ; Immunity, Innate/drug effects ; Interleukin-12/metabolism ; Leishmania major/immunology ; Leishmaniasis/immunology ; Leishmaniasis, Cutaneous/immunology ; Macrophages/immunology ; Macrophages/parasitology ; Mice ; Microspheres ; Mycobacterium/immunology ; Oligosaccharides/pharmacology ; Toll-Like Receptor 2/metabolism
Chemical Substances	Cytokines ; Oligosaccharides ; Toll-Like Receptor 2 ; Interleukin-12 (187348-17-0)
Language	English
Publishing date	2011-07-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2943-9
ISSN	1525-2191 ; 0002-9440
ISSN (online)	1525-2191
ISSN	0002-9440
DOI	10.1016/j.ajpath.2011.05.053
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Article ; Online: Transplacental transmission of Leishmania infantum as a means for continued disease incidence in North America.

Boggiatto, Paola Mercedes / Gibson-Corley, Katherine Nicole / Metz, Kyle / Gallup, Jack Michael / Hostetter, Jesse Michael / Mullin, Kathleen / Petersen, Christine Anne

PLoS neglected tropical diseases

2011 Volume 5, Issue 4, Page(s) e1019

Abstract: Background: Dogs are the predominant domestic reservoir for human L. infantum infection. Zoonotic ... transmitted by infected sand flies and phlebotomine sand flies exist in the United States, means of ongoing L. infantum ... A pregnant L. infantum-infected dam donated to Iowa State University gave birth in-house to 12 pups. Eight ...

Abstract	Background: Dogs are the predominant domestic reservoir for human L. infantum infection. Zoonotic visceral leishmaniasis (ZVL) is an emerging problem in some U.S. dog breeds, with an annual quantitative PCR prevalence of greater than 20% within an at-risk Foxhound population. Although classically Leishmania is transmitted by infected sand flies and phlebotomine sand flies exist in the United States, means of ongoing L. infantum transmission in U.S. dogs is currently unknown. Possibilities include vertical (transplacental/transmammary) and horizontal/venereal transmission. Several reports have indicated that endemic ZVL may be transmitted vertically. Aims: Our aims for this present study were to establish whether vertical/transplacental transmission was occurring in this population of Leishmania-infected US dogs and determine the effect that this means of transmission has on immune recognition of Leishmania. Methodology: A pregnant L. infantum-infected dam donated to Iowa State University gave birth in-house to 12 pups. Eight pups humanely euthanized at the time of birth and four pups and the dam humanely euthanized three months post-partum were studied via L. infantum-kinetoplast specific quantitative PCR (kqPCR), gross and histopathological assessment and CD4+ T cell proliferation assay. Key results: This novel report describes disseminated L. infantum parasites as identified by kqPCR in 8 day old pups born to a naturally-infected, seropositive U.S. dog with no travel history. This is the first report of vertical transmission of L. infantum in naturally-infected dogs in North America, emphasizing that this novel means of transmission could possibly sustain infection within populations. Major conclusions: Evidence that vertical transmission of ZVL may be a driving force for ongoing disease in an otherwise non-endemic region has significant implications on current control strategies for ZVL, as at present parasite elimination efforts in endemic areas are largely focused on vector-borne transmission between canines and people. Determining frequency of vertical transmission and incorporating canine sterilization with vector control may have a more significant impact on ZVL transmission to people in endemic areas than current control efforts.
MeSH term(s)	Animals ; CD4-Positive T-Lymphocytes/immunology ; Cell Proliferation ; DNA, Protozoan/genetics ; DNA, Protozoan/isolation & purification ; Dog Diseases/epidemiology ; Dog Diseases/transmission ; Dogs ; Female ; Infectious Disease Transmission, Vertical ; Leishmania infantum/genetics ; Leishmania infantum/immunology ; Leishmania infantum/isolation & purification ; Leishmaniasis, Visceral/epidemiology ; Leishmaniasis, Visceral/transmission ; Leishmaniasis, Visceral/veterinary ; Polymerase Chain Reaction ; Pregnancy ; Pregnancy Complications, Infectious/epidemiology ; Pregnancy Complications, Infectious/veterinary ; United States/epidemiology
Chemical Substances	DNA, Protozoan
Language	English
Publishing date	2011-04-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2429704-5
ISSN	1935-2735 ; 1935-2727
ISSN (online)	1935-2735
ISSN	1935-2727
DOI	10.1371/journal.pntd.0001019
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