Digital Commons Network^™

Definition Of An Hla-Dpw2-Restricted Epitope On Ns3, Recognized By A Dengue Virus Serotype-Cross-Reactive Human Cd4+ Cd8- Cytotoxic T-Cell Clone, Ichiro Kurane, Li Chen Dai, Peter G. Livingston, Elaine Reed, Francis A. Ennis

Li Dai

We previously reported that the clone JK34 was cross-reactive for dengue virus types 1, 2, 3, and 4 and recognized NS3 (I. Kurane, M. A. Brinton, A. L. Samson, and F. A. Ennis, J. Virol. 65:1823-1828, 1991). In the present experiments, we defined the epitope at the amino acid level, with 93 15-mer overlapping peptides which cover the entire NS3. A peptide 4 which contains amino acids 251 to 265 of NS3 sensitized the autologous B lymphoblastoid cell line (LCL) to the lysis by JK34. The smallest peptide recognized by JK34 was a 10-mer peptide which contains amino acids 255 …

Mutation Of Human Immunodeficiency Virus Type 1 At Amino Acid 585 On Gp41 Results In Loss Of Killing By Cd8+ A24-Restricted Cytotoxic T Lymphocytes, Li Chen Dai, Kim West, Rebecca A. Littaua, Kazuo Takahashi, Francis A. Ennis

Li Dai

A human leukocyte antigen A24-restricted CD8+ cytotoxic T-cell clone specific for gp41 of human immunodeficiency virus type 1 was isolated from an infected individual. The epitope was localized to amino acids 584 to 591 (YLKDQQLL, NL43 env sequence) of gp41 by using a panel of recombinant vaccinia viruses that contain truncated env genes and synthetic peptides. The clone killed autologous B-lymphoblastoid cell lines pulsed with a synthetic peptide reflecting the sequence of the IIIB and MN strains. This clone, however, failed to kill target cells pulsed with the peptides that have a mutation from Lys to Arg or Gln at …

Invited Commentary On: Orthotopic Heart Transplantation In Patients With Metabolic Risk Factors, Nicholas Cavarocchi, Paul Mather

Nicholas C Cavarocchi MDJ

This is invited commentary to the following article: Kilic, A., Conte, J. V., Shah, A. S., & Yuh, D. D. (2012). Orthotopic heart transplantation in patients with metabolic risk factors. Annals of Thoracic Surgery, 93(3), 718-724.

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

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

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 Double-Blind Randomized Controlled Trial Of Olanzapine Plus Sertraline Vs Olanzapine Plus Placebo For Psychotic Depression: The Study Of Pharmacotherapy Of Psychotic Depression (Stop-Pd), Barnett Meyers, Alastair Flint, Anthony Rothschild, Benoit Mulsant, Ellen Whyte, Catherine Peasley-Miklus, Eros Papademetriou, Andrew Leon, Moonseong Heo, Paul Appelbaum, Philip Candilis, Nancy Byatt, Kristina Deligiannidis

Philip J. Candilis

CONTEXT: Evidence for the efficacy of combination pharmacotherapy has been limited and without positive trials in geriatric patients with major depression (MD) with psychotic features. OBJECTIVES: To compare remission rates of MD with psychotic features in those treated with a combination of atypical antipsychotic medication plus a serotonin reuptake inhibitor with those treated with antipsychotic monotherapy; and to compare response by age. DESIGN: Twelve-week, double-blind, randomized, controlled trial. SETTING: Clinical services of 4 academic sites. Patients Two hundred fifty-nine subjects with MD with psychotic features randomized by age ( or =60 years) (mean [standard deviation (SD)], 41.3 [10.8] years in …

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

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 …

Treatment With Monoclonal Antibodies Against Clostridium Difficile Toxins, Israel Lowy, Deborah Molrine, Brett Leav, Barbara Blair, Roger Baxter, Dale Gerding, Geoffrey Nichol, William Thomas, Mark Leney, Susan Sloan, Catherine Hay, Donna Ambrosino

William D Thomas Jr

BACKGROUND: New therapies are needed to manage the increasing incidence, severity, and high rate of recurrence of Clostridium difficile infection.

METHODS: We performed a randomized, double-blind, placebo-controlled study of two neutralizing, fully human monoclonal antibodies against C. difficile toxins A (CDA1) and B (CDB1). The antibodies were administered together as a single infusion, each at a dose of 10 mg per kilogram of body weight, in patients with symptomatic C. difficile infection who were receiving either metronidazole or vancomycin. The primary outcome was laboratory-documented recurrence of infection during the 84 days after the administration of monoclonal antibodies or placebo.

RESULTS: …

Human Monoclonal Antibodies Directed Against Toxins A And B Prevent Clostridium Difficile-Induced Mortality In Hamsters, Gregory Babcock, Teresa Broering, Hector Hernandez, Robert Mandell, Katherine Donahue, Naomi Boatright, Anne Stack, Israel Lowy, Robert Graziano, Deborah Molrine, Donna Ambrosino, William Thomas

William D Thomas Jr

Clostridium difficile is the leading cause of nosocomial antibiotic-associated diarrhea, and recent outbreaks of strains with increased virulence underscore the importance of identifying novel approaches to treat and prevent relapse of Clostridium difficile-associated diarrhea (CDAD). CDAD pathology is induced by two exotoxins, toxin A and toxin B, which have been shown to be cytotoxic and, in the case of toxin A, enterotoxic. In this report we describe fully human monoclonal antibodies (HuMAbs) that neutralize these toxins and prevent disease in hamsters. Transgenic mice carrying human immunoglobulin genes were used to isolate HuMAbs that neutralize the cytotoxic effects of either toxin …

Amino Acids 270 To 510 Of The Severe Acute Respiratory Syndrome Coronavirus Spike Protein Are Required For Interaction With Receptor, Gregory Babcock, Diana Esshaki, William Thomas, Donna Ambrosino

William D Thomas Jr

A novel coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV), has recently been identified as the causative agent of severe acute respiratory syndrome (SARS). SARS-CoV appears similar to other coronaviruses in both virion structure and genome organization. It is known for other coronaviruses that the spike (S) glycoprotein is required for both viral attachment to permissive cells and for fusion of the viral envelope with the host cell membrane. Here we describe the construction and expression of a soluble codon-optimized SARS-CoV S glycoprotein comprising the first 1,190 amino acids of the native S glycoprotein (S(1190)). The codon-optimized and native S glycoproteins …

Gucy2c Opposes Systemic Genotoxic Tumorigenesis By Regulating Akt-Dependent Intestinal Barrier Integrity, Jieru Egeria Lin, Adam Eugene Snook, Peng Li, Brian Arthur Stoecker, Gilbert Won Kim, Michael Sullivan Magee, Alex Vladimir Mejia Garcia, Michael Anthony Valentino, Terry Hyslop, Stephanie Schulz, Scott Arthur Waldman

Adam E Snook

The barrier separating mucosal and systemic compartments comprises epithelial cells, annealed by tight junctions, limiting permeability. GUCY2C recently emerged as an intestinal tumor suppressor coordinating AKT1-dependent crypt-villus homeostasis. Here, the contribution of GUCY2C to barrier integrity opposing colitis and systemic tumorigenesis is defined. Mice deficient in GUCY2C (Gucy2c−/−) exhibited barrier hyperpermeability associated with reduced junctional proteins. Conversely, activation of GUCY2C in mice reduced barrier permeability associated with increased junctional proteins. Further, silencing GUCY2C exacerbated, while activation reduced, chemical barrier disruption and colitis. Moreover, eliminating GUCY2C amplified, while activation reduced, systemic oxidative DNA damage. This genotoxicity was associated with increased spontaneous …

Friends Of Nursing: A Community Of Caring To Promote Excellence In Nursing Practice, Education, And Research, Kim S. Hitchings Msn, Rn, Nea-Bc, Terry Capuano Rn, Svp, Clinical Services, Mary Ellen Herzog Med, Cfre, Cgms

Terry A Capuano MBA, MSN, RN, FACHE, NE-BC

More than 25 years ago, the name "Friends of Nursing" was adopted by an academic, community Magnet(®) hospital to signify a model for community support of nursing. From inception, the intent was to recruit philanthropic dollars to promote recognition of and excellence in nursing practice, education, and research. Although philanthropy in health care settings is common, what is unique about this program is the long-standing, dedicated conceptual framework for nursing philanthropy and the very significant number of philanthropic dollars from literally thousands of donors to support a diverse range of activities to affect and advance the professional excellence of nurses …

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

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

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

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

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 …

Managed Care, Hospice Use, Site Of Death, And Medical Expenditures In The Last Year Of Life, Ezekiel Emanuel, Arlene Ash, Wei Yu, Gail Gazelle, Norman Levinsky, Olga Saynina, Mark Mcclellan, Mark Moskowitz

wei yu

BACKGROUND: We examined deaths of Medicare beneficiaries in Massachusetts and California to evaluate the effect of managed care on the use of hospice and site of death and to determine how hospice affects the expenditures for the last year of life.

METHODS: Medicare data for beneficiaries in Massachusetts (n = 37 933) and California (n = 27 685) who died in 1996 were merged with each state's death certificate files to determine site and cause of death. Expenditure data were Health Care Financing Administration payments and were divided into 30-day periods from the date of death back 12 months.

RESULTS: …

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 …

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 …

Helping New Nurses Be Assertive About Patient Safety, S. Kinsella, K. Bigelow, S. Romano, Amy Sparks

Amy E.T. Sparks

No abstract provided.

Decreased Expression Of The Heat Shock Protein Hsp70-2 Is Associated With The Pathogenesis Of Male Infertility, H. Feng, J. Sandlow, Amy Sparks

Amy E.T. Sparks

OBJECTIVE: To examine the expression of the heat shock protein hsp70-2, and the possible relationship with the pathogenesis of male infertility. DESIGN: Prospective study. SETTING: Reproductive testing laboratory in a university hospital. PATIENT(S): Men undergoing testicular biopsy during an investigation of subfertility. INTERVENTION(S): Testicular tissues were obtained from biopsies of men undergoing infertility evaluation and subdivided into three groups: normal testes, maturational arrest and Sertoli cell-only syndrome. Immunostaining and Western blotting techniques determined expression of the heat shock protein hsp70-2 MAIN OUTCOME MEASURE(S): Expression of the heat shock protein hsp70-2 in the testes. RESULT(S): The experimental data demonstrated that the …

Semen Quality In Fertile Men In Relation To Psychosocial Stress, A. Gollenberg, F. Liu, C. Brazil, E. Drobnis, D. Guzick, J. Overstreet, J. Redmon, Amy Sparks, C. Wang, S. Swan

Amy E.T. Sparks

OBJECTIVE: To examine the association between stressful life events and semen parameters. DESIGN: Cross-sectional analysis in a pregnancy cohort study. SETTING: Prenatal clinics in five U.S. cities. PATIENT(S): Fertile men (n = 744) in the Study for Future Families, a cohort study of pregnant women and their partners. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Sperm concentration, percent motile, and percent normal morphology and classification above/below World Health Organization (WHO) cutoffs for semen quality. RESULT(S): After adjusting for confounders, men reporting 2+ recent stressful life events had an increased risk of being classified below WHO thresholds for "normal" defined by concentration, motility, …

Serum Inhibin-B In Fertile Men Is Strongly Correlated With Low But Not High Sperm Counts: A Coordinated Study Of 1,797 European And Us Men, N. Jorgensen, F. Liu, A. Andersson, M. Vierula, D. Irvine, J. Auger, C. Brazil, E. Drobnis, T. Jensen, P. Jouannet, J. Overstreet, J. Redmon, Amy Sparks, J. Toppari, C. Wang, N. Skakkebaek, S. Swan

Amy E.T. Sparks

OBJECTIVE: To describe associations between serum inhibin-b and sperm counts, adjusted for effect of time of blood sampling, in larger cohorts than have been previously reported. DESIGN: Cross-sectional studies of spermatogenesis markers. SETTING: Four European and four US centers. PATIENT(S): Fertile men (1,797) were included and examined from October 1996-February 2005. INTERVENTION(S): The study was observational and therefore without any intervention. MAIN OUTCOME MEASURE(S): Associations between inhibin-b and semen variables controlled for time of blood sampling and other covariates. RESULT(S): Inhibin-b decreased about 2.00% per hour from 8 am-12 pm and then about 3.25% per hour from 12 pm-4 pm. …

The Clinical Benefits Of The Bladder Scanner: A Research Synthesis, Amy Sparks, D. Boyer, A. Gambrel, M. Lovett, J. Johnson, T. Richards, J. Johnson, E. Grimm, C. Daniels, S. Tylka, H. Mattingly, M. Harper, D. Palermo

Amy E.T. Sparks

No abstract provided.

Decreased Expression Of The C-Kit Receptor Is Associated With Increased Apoptosis In Subfertile Human Testes, H. Feng, J. Sandlow, Amy Sparks, A. Sandra, L. Zheng

Amy E.T. Sparks

OBJECTIVE: To examine the expression of the c-kit receptor and its ligand, stem cell factor, and their possible relation with apoptosis in infertile men. DESIGN: Prospective laboratory study. SETTING: Urology laboratory in a university hospital. PATIENT(S): Men undergoing testicular biopsy during an investigation of subfertility. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Expression of the c-kit receptor protein, stem cell factor, and apoptosis in the testes. RESULT(S): The c-kit receptor was strongly present in Leydig cells and type A spermatogonia of normal testes, with decreased staining in Leydig cells and type A spermatogonia of testes with maturational arrest, and staining in only …