Medicine and Health Sciences Commons^™

Development And Characterization Of An Indoleamine 2,3-Dioxygenase (Ido) Deficient Mouse Model Of Preeclampsia, Mark Santillan, Christopher Pelham, Pimonrat Ketsawatsomkron, Donna Santillan, Baoli Yang, Stephen Hunter, Curt Sigmund

Donna A. Santillan

No abstract provided.

Single Umbilical Artery: Does Side Matter?., Mark Santillan, Donna Santillan, Diedre Fleener, Barbara Stegmann, Gideon Zamba, Stephen Hunter, Jerome Yankowitz

Donna A. Santillan

INTRODUCTION: The aim of this study was to determine if laterality of an absent umbilical artery (AUA) is associated with specific sonographic findings, chromosomal defects or postpartum birth defects. MATERIALS AND METHODS: In this retrospective cohort study, ultrasound reports and medical records of patients who received an obstetric ultrasound at the University of Iowa Hospitals and Clinics with an identified laterality of the AUA from 1989 to 2007 (n = 405) were reviewed. Rates of sonographic abnormalities between fetuses with a right versus left AUA were compared using Fisher's exact test. Adjustments for confounding were made using logistic regression modeling. …

The Association Between Hospital Obstetrical Volume And Maternal Postpartum Complications., Kathy L Kyser, Xin Lu, Donna Santillan, Mark Santillan, Stephen Hunter, Alison G Cahill, Peter Cram

Donna A. Santillan

OBJECTIVE: The purpose of this study was to examine the relationship between delivery volume and maternal complications.

STUDY DESIGN: We used administrative data to identify women who had been admitted for childbirth in 2006. Hospitals were stratified into deciles that were based on delivery volume. We compared composite complication rates across deciles.

RESULTS: We evaluated 1,683,754 childbirths in 1045 hospitals. Decile 1 and 2 hospitals had significantly higher rates of composite complications than decile 10 (11.8% and 10.1% vs 8.5%, respectively; P < .0001). Decile 9 and 10 hospitals had modestly higher composite complications as compared with decile 6 (8.8% and 8.5% vs 7.6%, respectively; P < .0001). Sixty percent of decile 1 and 2 hospitals were located within 25 miles of the nearest greater volume hospital.

CONCLUSION: Women who deliver at very low-volume hospitals have higher complication rates, as do women who deliver at …

Loss Of Mll Phd Finger 3 Is Necessary For Mll-Enl-Induced Hematopoietic Stem Cell Immortalization, J. Chen, Donna Santillan, M. Koonce, W. Wei, R. Luo, M. Thirman, N. Zeleznik-Le, M. Diaz

Donna A. Santillan

Reciprocal chromosomal translocations at the MLL gene locus result in expression of novel fusion proteins, such as MLL-ENL, associated with leukemia. The three PHD finger cassette, one of the highly conserved domains in MLL, is absent in all fusion proteins. This domain has been shown to interact with Cyp33, a cyclophilin which enhances the recruitment of histone deacetylases (HDAC) to the MLL repression domain and mediates HOX gene repression. Insertion of the third PHD finger of MLL into MLL-ENL allows the recruitment of Cyp33 and, subsequently, HDAC1 to the fusion protein. Furthermore, expression of the fusion protein with the PHD …

From Molecules To Medicine: A Future Cure For Preeclampsia?, Mark Santillan, Donna Santillan, Curt Sigmund, Stephen Hunter

Donna A. Santillan

In the United States, preeclampsia (PreE) affects 5-7% of all pregnancies, yet represents 15% of all maternal-fetal morbidity and mortality. PreE causes fetal growth restriction, oligohydramnios, fetal death, and maternal seizures, stroke, cerebrovascular hemorrhage and death. It has immediate and potentially long-term effects on both the fetus and mother. To date, the molecular pathogenesis of PreE is largely unknown. Multiple pathways, including dysfunctional angiogenesis, inappropriate placentation, oxidative stress and an altered immunological milieu have been proposed as key players in the development of PreE. In addition, genetic factors in all of these pathways are essential components in the etiology of …

Bromodomain And Histone Acetyltransferase Domain Specificities Control Mixed Lineage Leukemia Phenotype, Donna Santillan, C. Theisler, A. Ryan, R. Popovic, T. Stuart, M. Zhou, S. Alkan, N. Zeleznik-Le

Donna A. Santillan

A critical unanswered question about mixed lineage leukemia (MLL) is how specific MLL fusion partners control leukemia phenotype. The MLL-cyclic AMP-responsive element binding protein-binding protein (CBP) fusion requires both the CBP bromodomain and histone acetyltransferase (HAT) domain for transformation and causes acute myelogenous leukemia (AML), often preceded by a myelodysplastic phase. We did domain-swapping experiments to define whether unique specificities of these CBP domains drive this specific MLL phenotype. Within MLL-CBP, we replaced the CBP bromodomain or HAT domain with P300/CBP-associated factor (P/CAF) or TAF(II)250 bromodomains or the P/CAF or GCN5 HAT domains. HAT, but not bromodomain, substitutions conferred enhanced …

Noninvasive Whole-Genome Sequencing Of A Human Fetus, J. Kitzman, M. Snyder, M. Ventura, A. Lewis, R. Qiu, L. Simmons, H. Gammill, C. Rubens, Donna Santillan, J. Murray, H. Tabor, M. Bamshad, E. Eichler, J. Shendure

Donna A. Santillan

Analysis of cell-free fetal DNA in maternal plasma holds promise for the development of noninvasive prenatal genetic diagnostics. Previous studies have been restricted to detection of fetal trisomies, to specific paternally inherited mutations, or to genotyping common polymorphisms using material obtained invasively, for example, through chorionic villus sampling. Here, we combine genome sequencing of two parents, genome-wide maternal haplotyping, and deep sequencing of maternal plasma DNA to noninvasively determine the genome sequence of a human fetus at 18.5 weeks of gestation. Inheritance was predicted at 2.8 x 10(6) parental heterozygous sites with 98.1% accuracy. Furthermore, 39 of 44 de novo …

Cell Encapsulation As A Potential Nondietary Therapy For Maternal Phenylketonuria, Donna Santillan, Mark Santillan, Stephen Hunter

Donna A. Santillan

OBJECTIVE: The objective of this work was to determine whether cells overexpressing phenylalanine (Phe) hydroxylase (PAH) can significantly reduce Phe in vitro for potential use as a therapy for preventing maternal phenylketonuria. STUDY DESIGN: Human 293T and WRL68 cell lines were transiently and stably transfected to overexpress PAH. Cells were encapsulated within microspheres of sodium alginate. Timed measurements of Phe in media were performed using tandem mass spectrometry. RESULTS: Both nonencapsulated and encapsulated transiently transfected cells overexpressing PAH significantly reduced the Phe concentration in media by approximately 50% in comparison to mock-transfected cells. Cell line clones stably expressing PAH significantly …

Efficacy Of Polymeric Encapsulated C5a Peptidase-Based Group B Streptococcus Vaccines In A Murine Model, Donna Santillan, K. Rai, Mark Santillan, Y. Krishnamachari, A. Salem, S. Hunter

Donna A. Santillan

OBJECTIVE: The purpose was to examine in mice the efficacy of various polymeric-encapsulated C5a peptidase vaccine formulations in eliciting a long-term immune response and preventing group B streptococcus (GBS) infection. STUDY DESIGN: C5a peptidase was encapsulated in semipermeable microspheres of poly(lactide-coglycolide) (PLGA). Female ICR mice were immunized with 0, 10, or 30 mug of encapsulated C5a peptidase within 2 different formulations of PLGA polymers. Booster doses were given at weeks 4 and 8. Antibody responses were measured by enzyme-linked immunosorbent assay at weeks 4, 8, 11, and 40. Vaginal challenges with GBS types 1a, III, and V were performed at …

The Mll Fusion Gene, Mll-Af4, Regulates Cyclin-Dependent Kinase Inhibitor Cdkn1b (P27(Kip1)) Expression, Z. Xia, R. Popovic, J. Chen, C. Theisler, T. Stuart, Donna Santillan, F. Erfurth, M. Diaz, N. Zeleznik-Le

Donna A. Santillan

No abstract provided.

New Cdc Group B Streptococcal (Gbs) Guidelines, Mark Santillan, Donna Santillan

Donna A. Santillan

No abstract provided.