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Bilateral Renal Artery Thrombosis Secondary To Blunt Trauma: Case Report And Review Of The Literature., P Frassinelli, Michael D. Pasquale Md, Facs, Fccm, C Reckard, J Goodreau, G Sherwin Jun 2016

Bilateral Renal Artery Thrombosis Secondary To Blunt Trauma: Case Report And Review Of The Literature., P Frassinelli, Michael D. Pasquale Md, Facs, Fccm, C Reckard, J Goodreau, G Sherwin

Michael D Pasquale MD, FACS, FCCM

No abstract provided.


The Effect Of A Family Support Intervention On Family Satisfaction, Length-Of-Stay, And Cost Of Care In The Intensive Care Unit, Wayne Shelton, Crystal Moore, Sophia Socaris, Jian Gao, Jane Dowling Mar 2016

The Effect Of A Family Support Intervention On Family Satisfaction, Length-Of-Stay, And Cost Of Care In The Intensive Care Unit, Wayne Shelton, Crystal Moore, Sophia Socaris, Jian Gao, Jane Dowling

Crystal Moore

OBJECTIVE: The study examined the effect of adding a full-time family support coordinator to the surgical intensive care unit team on family satisfaction, length-of-stay, and cost in the surgical intensive care unit. DESIGN, SETTING, AND PATIENTS: A quasi-experimental design was conducted in two phases: baseline (8 mos) and intervention (10 mos) phases. Data on family satisfaction, length-of-stay, and costs from both phases were collected. INTERVENTIONS: The intervention added a new role, the family support coordinator, to the surgical intensive care unit team. The family support coordinator functioned as a liaison between the patient's family and the health care team. MEASUREMENTS …


Applying Osteopathic Principles To Formulate Treatment For Patients With Chronic Pain, Michael Kuchera Dec 2015

Applying Osteopathic Principles To Formulate Treatment For Patients With Chronic Pain, Michael Kuchera

Michael Kuchera

Osteopathic manipulative medicine (OMM) is a physician-directed approach to patient care that incorporates diagnostic and therapeutic strategies to address body unity issues, enhance homeostatic mechanisms, and maximize structure-function interrelationships. Osteopathic physicians integrate a thorough medical history with palpatory examination of a patient to ascertain distinctive characteristics and origins of the patient's pain, to evaluate how pain uniquely affects the patient, and to determine whether segmental, reflex, or triggered pain phenomena coexist in the patient. Osteopathic manipulative medicine expands differential diagnoses by allowing the physician to consider somatic dysfunction and implement treatment options via integration of specific aspects of complementary care …


Hysteresis As A Measure Of Ankle Dysfunction, Alissa Cohen, James Mertz, Peggy Stewart, Michael Warner, Michael Kuchera Dec 2015

Hysteresis As A Measure Of Ankle Dysfunction, Alissa Cohen, James Mertz, Peggy Stewart, Michael Warner, Michael Kuchera

Michael Kuchera

There is no abstract for this article.


A Comparative Study Of Cervical Hysteresis Characteristics After Various Osteopathic Manipulative Treatment (Omt) Modalities, Precious Barnes, Francisco Laboy, Lauren Noto-Bell, Veronica Ferencz, Jeffrey Nelson, Michael Kuchera Dec 2015

A Comparative Study Of Cervical Hysteresis Characteristics After Various Osteopathic Manipulative Treatment (Omt) Modalities, Precious Barnes, Francisco Laboy, Lauren Noto-Bell, Veronica Ferencz, Jeffrey Nelson, Michael Kuchera

Michael Kuchera

BACKGROUND: Few objective measures have been used to document change in myofascial tissues after OMT.

HYPOTHESIS: Paraspinal tissues associated with cervical somatic dysfunction (SD) will demonstrate quantifiable change in myofascial hysteresis characteristics after a given OMT technique but not after a Sham intervention.

MATERIALS AND METHODS: 240 subjects were palpated for cervical articular SD. A randomly selected intervention (5 OMT techniques or a Sham) was applied to the cervical SD clinically considered to be most severe. A durometer (SA201(®); Sigma Instruments, Cranberry, PA, USA) objectively measured myofascial structures overlying each cervical spinal segment pre- and post- intervention. Using a …


Osteopathic Evaluation And Manipulative Treatment In Reducing The Morbidity Of Otitis Media: A Pilot Study, Brian Degenhardt, Michael Kuchera Dec 2015

Osteopathic Evaluation And Manipulative Treatment In Reducing The Morbidity Of Otitis Media: A Pilot Study, Brian Degenhardt, Michael Kuchera

Michael Kuchera

OBJECTIVE: To study the effects of osteopathic manipulative treatment in routine pediatric care for children with recurrent acute otitis media. STUDY DESIGN: Pilot cohort study with 1-year posttreatment follow-up. At follow-up, subjects' parents or legal guardians and their referring and/or family physicians were contacted to determine recurrence of otitis media since intervention. Subjects: A referred and volunteer sample of pediatric patients ranging in age from 7 months to 35 months with a history of recurrent otitis media (N=8). INTERVENTION: For 3 weeks, all subjects received weekly osteopathic structural examinations and osteopathic manipulative treatment. This intervention was performed concurrently with traditional …


The Unique Contribution Of Behavioral Scientists To Medical Education: The Top Ten Competencies., Jeffrey L. Sternlieb Phd Jul 2015

The Unique Contribution Of Behavioral Scientists To Medical Education: The Top Ten Competencies., Jeffrey L. Sternlieb Phd

Jeffrey L Sternlieb PhD

Understandably, the focus of most physicians is primarily on the biomedical-What is this disease or injury? Behavioral scientists from various disciplines in medical education generally have a broader approach-Who is this person with these symptoms and what is their story? Since behavioral scientists are often alone among U. S. residency faculty, physicians may fail to recognize the value of their approach to medical resident training. This review identifies and describes the top areas of expertise that behavioral scientists bring to medical education and how their training prepares them to think differently than other medical educators. In the course of identifying …


Evaluation And Management Of Mild Traumatic Brain Injury: An Eastern Association For The Surgery Of Trauma Practice Management Guideline., Ronald J. Bross Md, Randeep Jawa, Jennifer M Watters, Jennifer C. Knight, Andrew J Kerwin, Eleanor S Winston, Robert D. Barraco Md, Brian Tucker, James M Bardes, Susan E Rowell Mar 2015

Evaluation And Management Of Mild Traumatic Brain Injury: An Eastern Association For The Surgery Of Trauma Practice Management Guideline., Ronald J. Bross Md, Randeep Jawa, Jennifer M Watters, Jennifer C. Knight, Andrew J Kerwin, Eleanor S Winston, Robert D. Barraco Md, Brian Tucker, James M Bardes, Susan E Rowell

Robert D Barraco MD, MPH

BACKGROUND: An estimated 1.1 million people sustain a mild traumatic brain injury (MTBI) annually in the United States. The natural history of MTBI remains poorly characterized, and its optimal clinical management is unclear. The Eastern Association for the Surgery of Trauma had previously published a set of practice management guidelines for MTBI in 2001. The purpose of this review was to update these guidelines to reflect the literature published since that time. METHODS: The PubMed and Cochrane Library databases were searched for articles related to MTBI published between 1998 and 2011. Selected older references were also examined. RESULTS: A total …


Evaluation And Management Of Mild Traumatic Brain Injury: An Eastern Association For The Surgery Of Trauma Practice Management Guideline., Ronald J. Bross Md, Randeep Jawa, Jennifer M Watters, Jennifer C. Knight, Andrew J Kerwin, Eleanor S Winston, Robert D. Barraco Md, Brian Tucker, James M Bardes, Susan E Rowell Mar 2015

Evaluation And Management Of Mild Traumatic Brain Injury: An Eastern Association For The Surgery Of Trauma Practice Management Guideline., Ronald J. Bross Md, Randeep Jawa, Jennifer M Watters, Jennifer C. Knight, Andrew J Kerwin, Eleanor S Winston, Robert D. Barraco Md, Brian Tucker, James M Bardes, Susan E Rowell

Robert D Barraco MD, MPH

BACKGROUND: An estimated 1.1 million people sustain a mild traumatic brain injury (MTBI) annually in the United States. The natural history of MTBI remains poorly characterized, and its optimal clinical management is unclear. The Eastern Association for the Surgery of Trauma had previously published a set of practice management guidelines for MTBI in 2001. The purpose of this review was to update these guidelines to reflect the literature published since that time. METHODS: The PubMed and Cochrane Library databases were searched for articles related to MTBI published between 1998 and 2011. Selected older references were also examined. RESULTS: A total …


Analysis Of The Frequency And Severity Of Rear-End Crashes In Work Zones, Yi Qi, Raghavan Srinivasan, Hualiang Teng, Robert Baker Nov 2014

Analysis Of The Frequency And Severity Of Rear-End Crashes In Work Zones, Yi Qi, Raghavan Srinivasan, Hualiang Teng, Robert Baker

Yi Qi

OBJECTIVE: The objective of this study was to identify the factors that influence the frequency and severity of rear-end crashes in work zones because rear-end crashes represent a significant proportion of crashes that occur in work zones. METHODS: Truncated count data models were developed to identify influencing factors on the frequency of rear-end crashes in work zones and ordered probit models were developed to evaluate influencing factors on the severity of rear-end crashes in work zones. RESULTS: Most of the variables identified in this study for these 2 models were significant at the 95 percent level. The statistics for models …


Novel Ubiquitin Neuropathology In Frontotemporal Dementia With Valosin-Containing Protein Gene Mutations, Mark Forman, Ian Mackenzie, Nigel Cairns, Eric Swanson, Philip Boyer, David Drachman, Bharati Jhaveri, Jason Karlawish, Alan Pestronk, Thomas Smith, Pang-Hsien Tu, Giles Watts, William Markesbery, Charles Smith, Virginia Kimonis Nov 2014

Novel Ubiquitin Neuropathology In Frontotemporal Dementia With Valosin-Containing Protein Gene Mutations, Mark Forman, Ian Mackenzie, Nigel Cairns, Eric Swanson, Philip Boyer, David Drachman, Bharati Jhaveri, Jason Karlawish, Alan Pestronk, Thomas Smith, Pang-Hsien Tu, Giles Watts, William Markesbery, Charles Smith, Virginia Kimonis

Jason Karlawish

Frontotemporal dementia (FTD) with inclusion body myopathy and Paget disease of bone (IBMPFD) is a rare, autosomal-dominant disorder caused by mutations in the valosin-containing protein (VCP) gene, a member of the AAA-ATPase gene superfamily. The neuropathology associated with sporadic FTD is heterogeneous and includes tauopathies and frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U). However, there is limited information on the neuropathology in IBMPFD. We performed a detailed, systematic analysis of the neuropathologic changes in 8 patients with VCP mutations. A novel pattern of ubiquitin pathology was identified in IBMPFD that was distinct from sporadic and familial FTLD-U without VCP gene …


National Trauma Institute Prospective Evaluation Of The Ventilator Bundle In Trauma Patients: Does It Really Work?, Martin A. Croce Md, Karen J. Brasel Md, Mph, Raul Coimbra Md, Phd, Charles A. Adams Jr, Md, Preston R. Miller Md, Michael D. Pasquale Md, Facs, Fccm, Chanchai S. Mcdonald Phd, Somchan Vuthipadadon Phd, Timothy C. Fabian Md, Elizabeth A. Tolley Phd Sep 2014

National Trauma Institute Prospective Evaluation Of The Ventilator Bundle In Trauma Patients: Does It Really Work?, Martin A. Croce Md, Karen J. Brasel Md, Mph, Raul Coimbra Md, Phd, Charles A. Adams Jr, Md, Preston R. Miller Md, Michael D. Pasquale Md, Facs, Fccm, Chanchai S. Mcdonald Phd, Somchan Vuthipadadon Phd, Timothy C. Fabian Md, Elizabeth A. Tolley Phd

Michael D Pasquale MD, FACS, FCCM

BACKGROUND: Since its introduction by the Institute for Healthcare Improvement, the ventilator bundle (VB) has been credited with a reduction in ventilator-associated pneumonia (VAP). The VB consists of stress ulcer prophylaxis, deep venous thrombosis prophylaxis, head-of-bed elevation, and daily sedation vacation with weaning assessment. While there is little compelling evidence that the VB is effective, it has been widely accepted. The Centers for Medical and Medicaid Services has suggested that VAP should be a "never event" and may reduce payment to providers. To provide evidence of its efficacy, the National Trauma Institute organized a prospective multi-institutional trial to evaluate the …


Pseudohypoparathyroidism Type 1a And Insulin Resistance In A Child, Benjamin U. Nwosu, Mary M. Lee Sep 2014

Pseudohypoparathyroidism Type 1a And Insulin Resistance In A Child, Benjamin U. Nwosu, Mary M. Lee

Mary M. Lee

Background. A 5-year-old white girl with a history of hypothyroidism in infancy presented to the endocrinology clinic of a tertiary hospital. Her physical examination noted a stocky physique, broad chest, short neck and short digits. Two years later, skin examination revealed subcutaneous nodules and acanthosis nigricans. Investigations. Measurement of levels of serum phosphate, parathyroid hormone, ionized calcium and insulin; measurement of peak growth hormone by the arginine-levodopa stimulation test; calculation of homeostasis model assessment of insulin resistance; assessment of bone age; DNA analysis of the GNAS gene. Diagnosis. Pseudohypoparathyroidism type 1a in a patient with Albright hereditary osteodystrophy, characterized by …


Depression Screening Of Perinatal Women By The Des Moines Healthy Start Project: Program Description And Evaluation, Lisa Segre, M. O'Hara, R. Brock, D. Taylor Aug 2014

Depression Screening Of Perinatal Women By The Des Moines Healthy Start Project: Program Description And Evaluation, Lisa Segre, M. O'Hara, R. Brock, D. Taylor

Lisa S. Segre

OBJECTIVE: Maternal depression is linked to poor infant and child outcome. In 2001, the U.S. Health Resources and Services Administration required all Healthy Start programs to incorporate maternal-depression screening as part of home visiting services. This article describes the implementation and results of depression screening by the Des Moines Healthy Start Project between 2002 and 2009. The study represents the first longitudinal assessment of the Healthy Start maternal-depression screening initiative. METHODS: The evaluation assessed staff compliance with a protocol for screening for depression among clients at regular intervals during the prenatal and postnatal periods until the client's child was two …


Assessment Of Human Cd4+ And Cd8+ T Lymphocyte Responses In Experimental Viral Vaccine Studies, Alan Rothman, Y. Yamada, Julie Jameson, John Cruz, Kim West, Sharone Green, Francis Ennis Aug 2014

Assessment Of Human Cd4+ And Cd8+ T Lymphocyte Responses In Experimental Viral Vaccine Studies, Alan Rothman, Y. Yamada, Julie Jameson, John Cruz, Kim West, Sharone Green, Francis Ennis

Alan Rothman

The traditional in vitro correlate of immunological protection is the induction by a vaccine of neutralizing antibodies against the virus. It was formerly assumed that protection induced by a vaccine was solely due to neutralizing antibodies. Neutralizing antibodies are potent in the prevention of certain diseases, but virus-specific CD4+ T helper cells aid in the proliferation of specific antigen-triggered B cells to make antibodies. CD8+ T cells are responsible for eliminating virus-infected cells during viral illness, and may act as a second line of defence by becoming activated and eliminating any cells that become infected despite the presence of neutralizing …


Assessment Of Human Cd4+ And Cd8+ T Lymphocyte Responses In Experimental Viral Vaccine Studies, Alan Rothman, Y. Yamada, Julie Jameson, John Cruz, Kim West, Sharone Green, Francis Ennis Jan 2014

Assessment Of Human Cd4+ And Cd8+ T Lymphocyte Responses In Experimental Viral Vaccine Studies, Alan Rothman, Y. Yamada, Julie Jameson, John Cruz, Kim West, Sharone Green, Francis Ennis

Sharone Green

The traditional in vitro correlate of immunological protection is the induction by a vaccine of neutralizing antibodies against the virus. It was formerly assumed that protection induced by a vaccine was solely due to neutralizing antibodies. Neutralizing antibodies are potent in the prevention of certain diseases, but virus-specific CD4+ T helper cells aid in the proliferation of specific antigen-triggered B cells to make antibodies. CD8+ T cells are responsible for eliminating virus-infected cells during viral illness, and may act as a second line of defence by becoming activated and eliminating any cells that become infected despite the presence of neutralizing …


The Changing Pattern Of Neonatal Mortality In A Regionalized System Of Perinatal Care: A Current Update., H. Hein, Maria Lofgren Nov 2013

The Changing Pattern Of Neonatal Mortality In A Regionalized System Of Perinatal Care: A Current Update., H. Hein, Maria Lofgren

Maria A Lofgren

OBJECTIVE: Our earlier studies about the changing pattern of neonatal mortality were based on data from 1978-1979 and 1982-1983. In this report, we provide a modern update of the causes of neonatal deaths to help focus prevention measures. STUDY DESIGN: We reviewed neonatal deaths for the years 1995 and 1996 and assigned a clinical cause of death. Deaths were reviewed and analyzed by place of birth and death, according to level of care. We provided an estimate of the change in causes of death between 1982-1983 and 1995-1996 and calculated an idealized neonatal mortality rate for each level of care …


Development Of A Resource Manual For Returning Neonates To Community Hospitals., Maria Lofgren Nov 2013

Development Of A Resource Manual For Returning Neonates To Community Hospitals., Maria Lofgren

Maria A Lofgren

To facilitate the transfer of an infant from a tertiary NICU to a community Level II hospital for convalescing follow-up care, the tertiary staff must know the referral center's capabilities. This will help to establish a trusting relationship between hospitals, will enable the tertiary staff to send infants back to the referral center in a timely manner, will enable them to reassure the patient's parents concerning the transfer, and will facilitate communication between the hospitals and the patient's family. This article describes the development of a referring hospital resource manual designed to facilitate the transfer process.


Innovative University Partnership Meets Neonatal Nurse Practitioner Program Need Amid Faculty Shortage, Rebecca Siewert, L. Rasmussen, Maria Lofgren, Patricia Clinton Nov 2013

Innovative University Partnership Meets Neonatal Nurse Practitioner Program Need Amid Faculty Shortage, Rebecca Siewert, L. Rasmussen, Maria Lofgren, Patricia Clinton

Maria A Lofgren

This nation is facing a significant nursing faculty shortage not only at the undergraduate but also at the graduate level. As nursing faculty, we must be innovative in considering ways of consolidating resources in this time of demand for advanced practice nurses. With the apparent need for qualified neonatal nurse practitioners in Iowa, the University of Iowa understood the importance of starting a neonatal nurse practitioners program. The University of Iowa College of Nursing and the University of Missouri-Kansas City formed a partnership to educate neonatal nurse practitioners. Although this partnership concentrates on a specific subspecialty population, it can serve …


A Review Of The Literature On Multiple Symptoms, Their Predictors, And Associated Outcomes In Patients With Advanced Cancer, Stephanie Gilbertson-White, B. Aouizerat, T. Jahan, C. Miaskowski Nov 2013

A Review Of The Literature On Multiple Symptoms, Their Predictors, And Associated Outcomes In Patients With Advanced Cancer, Stephanie Gilbertson-White, B. Aouizerat, T. Jahan, C. Miaskowski

Stephanie Gilbertson-White

OBJECTIVE: The findings from several studies suggest that palliative care patients with advanced cancer experience multiple symptoms, and that these symptoms may be related to demographic and clinical factors as well as to patient outcomes. However, no systematic review has summarized the findings from studies that assessed multiple symptoms, predictors, and outcomes in these patients. The purposes of this review, focused on palliative care patients with advanced cancer, are to: 1) describe the relationships among multiple symptoms; 2) describe the predictors of multiple symptoms; and 3) describe the relationships between multiple symptoms and patient outcomes. METHOD: Comprehensive literature searches were …


The Association Between Hospital Obstetrical Volume And Maternal Postpartum Complications, Kathy Kyser, Xin Lu, Donna Santillan, Mark Santillan, Stephen Hunter, Alison Cahill, Peter Cram Sep 2013

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

Stephen K. Hunter

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 …


The Gamete And Embryo Compatibility Of Various Synthetic Polymers., Stephen Hunter, J. Scott, D. Hull, R. Urry Jul 2013

The Gamete And Embryo Compatibility Of Various Synthetic Polymers., Stephen Hunter, J. Scott, D. Hull, R. Urry

Stephen K. Hunter

Several popular and well-characterized polymeric materials were evaluated for their biocompatibility toward the cells unique to reproduction. To accomplish these studies, several in vitro tests were developed that evaluated biocompatibility between the polymers and spermatozoa, ova, and embryos. The data indicated significant differences between the materials with respect to their biocompatibility toward sperm motility, the sperm's ability to penetrate zona-free hamster eggs, and the ability of two-cell mouse embryos to divide. Polytetrafluoroethylene (PTFE-Teflon; PTFE, Chemplast Inc., Wayne, NJ), polyethylene glycol (PEG), and polyhydroxyethyl methacrylate (PHEMA) appear to be the most inert of the materials studied. Polyvinyl chloride (PVC; Tygon-Norton, Akron, …


Cell Encapsulation As A Potential Nondietary Therapy For Maternal Phenylketonuria, Donna Santillan, Mark Santillan, Stephen Hunter Jul 2013

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

Stephen K. Hunter

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 …


Appropriate Tissue- And Cell-Specific Expression Of A Single Copy Human Angiotensinogen Transgene Specifically Targeted Upstream Of The Hprt Locus By Homologous Recombination., B. Cvetkovic, Baoli Yang, R. Williamson, C. Sigmund Jul 2013

Appropriate Tissue- And Cell-Specific Expression Of A Single Copy Human Angiotensinogen Transgene Specifically Targeted Upstream Of The Hprt Locus By Homologous Recombination., B. Cvetkovic, Baoli Yang, R. Williamson, C. Sigmund

Baoli Yang

Development of experimental models by genetic manipulation in mice has proven to be very useful in determining the significance of particular genes in the development of or susceptibility to hypertension. Advances in molecular genetics, transgenic mouse technology, and physiological measurements in mice provided an opportunity to go a step further and develop models to analyze the physiological significance of specific gene variants potentially causing hypertension. In this report, we describe the development of a human angiotensinogen transgenic mouse model generated by targeting the human angiotensinogen gene upstream of the mouse HPRT locus by homologous recombination. The main benefit of this …


Regulation Of Terminal Deoxynucleotidyl Transferase Gene Expression In Mice And Men., M. Coleman, Baoli Yang, D. Sorscher Jul 2013

Regulation Of Terminal Deoxynucleotidyl Transferase Gene Expression In Mice And Men., M. Coleman, Baoli Yang, D. Sorscher

Baoli Yang

A nontemplate directed DNA polymerase, terminal deoxynucleotidyl transferase (terminal transferase) is expressed in a tissue-specific and development stage-specific manner. Its enzymatic properties and tissue localization have implicated the protein in development of normal immune function. Significant progress has been made in understanding the enzymology and important domains of this protein. More recently, studies have focused on regulation of the gene that codes for the protein in mice and humans. The murine gene has yielded to these studies more readily than the human gene. A murine basal promoter element has been identified along with several trans-acting protein factors that may regulate …


Mutational Analysis Of Residues In The Nucleotide Binding Domain Of Human Terminal Deoxynucleotidyl Transferase., Baoli Yang, K. Gathy, M. Coleman Jul 2013

Mutational Analysis Of Residues In The Nucleotide Binding Domain Of Human Terminal Deoxynucleotidyl Transferase., Baoli Yang, K. Gathy, M. Coleman

Baoli Yang

Human terminal deoxynucleotidyl transferase (TdT) was overexpressed in a baculovirus system. The pure recombinant enzyme was identical in size, activity, kinetic constants, and metal effects to native enzyme. Three amino acids, within either the putative nucleotide binding domain and part of a DNA polymerase consensus sequence, YGDTDSLF, or a TdT consensus sequence, GGFRRGK, were altered by site-directed mutagenesis. The four mutant forms of terminal transferase were also overexpressed in the baculovirus expression system and purified from Trichoplusia ni larvae by a monoclonal antibody affinity column and compared with wild-type enzyme with respect to thermostabilities, secondary structure, metal effects, and kinetic …


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 Jun 2013

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 Jun 2013

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 …


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 Jun 2013

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 Jun 2013

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 …