Digital Commons Network^™

Erythroid Cell-Specific Α-Globin Gene Regulation By The Cp2 Transcription Factor Family, Ho C. Kang, Jui Hyung Chae, Yeon H. Lee, Mi-Ae Park, June Ho Shin, Sung-Hyun Kim, Sang-Kyu Ye, Yoon Shin Cho, Steven Fiering, Chul Geun Kim

Dartmouth Scholarship

We previously demonstrated that ubiquitously expressed CP2c exerts potent erythroid-specific transactivation of alpha-globin through an unknown mechanism. This mechanism is reported here to involve specific CP2 splice variants and protein inhibitor of activated STAT1 (PIAS1). We identify a novel murine splice isoform of CP2, CP2b, which is identical to CP2a except that it has an additional 36 amino acids encoded by an extra exon. CP2b has an erythroid cell-specific transcriptional activation domain, which requires the extra exon and can form heteromeric complexes with other CP2 isoforms, but lacks the DNA binding activity found in CP2a and CP2c. Transcriptional activation of …

Avoiding Versus Seeking: The Relationship Of Information Seeking To Avoidance, Blunting, Coping, Dissonance, And Related Concepts, Donald O. Case, James E. Andrews, J. David Johnson, Suzanne L. Allard

Information Science Faculty Publications

QUESTION: How have theorists and empirical researchers treated the human tendency to avoid discomforting information?

DATA SOURCES: A historical review (1890-2004) of theory literature in communication and information studies, coupled with searches of recent studies on uptake of genetic testing and on coping strategies of cancer patients, was performed.

STUDY SELECTION: The authors' review of the recent literature included searches of the MEDLINE, PsychInfo, and CINAHL databases between 1992 and summer of 2004 and selective, manual searches of earlier literature. Search strategies included the following subject headings and key words: MeSH headings: Genetic Screening/psychology, Decision Making, Neoplasms/diagnosis/genetics/psychology; CINAHL headings: Genetic …

A Model Program For Youth Suicide Prevention, Hatim A. Omar

Pediatrics Faculty Publications

Youth suicide continues to be one of the leading causes of death in the United States. Nation wide it is the third leading cause of death in the 10-24 year old age group. The rate of suicide varies somewhat from state to state. In the state of Kentucky, youth suicide is the second leading cause of death. This article describes a grass root, community-based program for youth suicide prevention and its impact on the community. The Stop Youth Suicide Campaign was launched in October 2000 and included more than 30 local agencies. This program worked. through public education, education of …

A Human T-Cell Lymphotropic Virus Type 1 Enhancer Of Myc Transforming Potential Stabilizes Myc-Tip60 Transcriptional Interactions, Soumya Awasthi, Anima Sharma, Kasuen Wong, Junyu Zhang, Elizabeth F. Matlock, Lowery Rogers, Pamela Motloch, Shigeki Takemoto, Hirokuni Taguchi, Michael D. Cole

Dartmouth Scholarship

The human T-cell lymphotropic virus type 1 (HTLV-1) infects and transforms CD4+ lymphocytes and causes adult T-cell leukemia/lymphoma (ATLL), an aggressive lymphoproliferative disease that is often fatal. Here, we demonstrate that the HTLV-1 pX splice-variant p30II markedly enhances the transforming potential of Myc and transcriptionally activates the human cyclin D2 promoter, dependent upon its conserved Myc-responsive E-box enhancer elements, which are associated with increased S-phase entry and multinucleation. Enhancement of c-Myc transforming activity by HTLV-1 p30II is dependent upon the transcriptional coactivators, transforming transcriptional activator protein/p434 and TIP60, and it requires TIP60 histone acetyltransferase (HAT) activity and correlates with the …

Avoiding Versus Seeking: The Relationship Of Information Seeking To Avoidance, Blunting, Coping, Dissonance, And Related Concepts, Donald O. Case, James E. Andrews, J. David Johnson, Suzanne L. Allard

School of Information Faculty Publications

QUESTION: How have theorists and empirical researchers treated the human tendency to avoid discomforting information?

DATA SOURCES: A historical review (1890-2004) of theory literature in communication and information studies, coupled with searches of recent studies on uptake of genetic testing and on coping strategies of cancer patients, was performed.

STUDY SELECTION: The authors' review of the recent literature included searches of the MEDLINE, PsychInfo, and CINAHL databases between 1992 and summer of 2004 and selective, manual searches of earlier literature. Search strategies included the following subject headings and key words: MeSH headings: Genetic Screening/psychology, Decision Making, Neoplasms/diagnosis/genetics/psychology; CINAHL headings: Genetic …

Pathways To Ptsd, Part Ii: Sexually Abused Children, Julie B Kaplow, Kenneth A Dodge, Lisa Amaya-Jackson, Glenn N Saxe

Faculty, Staff and Students Publications

OBJECTIVE: The goal of this research was to develop and test a prospective model of posttraumatic stress symptoms in sexually abused children that includes pretrauma, trauma, and disclosure-related pathways.

METHOD: At time 1, several measures were used to assess pretrauma variables, trauma variables, and stress reactions upon disclosure for 156 sexually abused children ages 8 to 13 years. At the time 2 follow-up (7 to 36 months following the initial interview), the children were assessed for posttraumatic stress disorder (PTSD) symptoms.

RESULTS: A path analysis involving a series of hierarchically nested ordinary least squares multiple regression analyses indicated three direct …

Gonadal Steroids Differentially Modulate Neurotoxicity Of Hiv And Cocaine: Testosterone And Ici 182,780 Sensitive Mechanism, Sherie L. Kendall, Caroline F. Anderson, Avindra Nath, Jadwiga Turchan-Cholewo, Cantey L. Land, Charles F. Mactutus, Rosemarie M. Booze

Behavioral Science Faculty Publications

BACKGROUND: HIV Associated Dementia (HAD) is a common complication of human immunodeficiency virus (HIV) infection that erodes the quality of life for patients and burdens health care providers. Intravenous drug use is a major route of HIV transmission, and drug use is associated with increased HAD. Specific proteins released as a consequence of HIV infection (e.g., gp120, the HIV envelope protein and Tat, the nuclear transactivating protein) have been implicated in the pathogenesis of HAD. In primary cultures of human fetal brain tissue, subtoxic doses of gp120 and Tat are capable of interacting with a physiologically relevant dose of cocaine, …

A Critical Role For Kalirin In Ngf Signaling Through Trka, Kausik Chakrabarti, Rong Lin, Noraisha I. Schiller, Yanping Wang, David Koubi, Ying-Xin Fan, Brian B. Rudkin, Gibbes R. Johnson, Martin R. Schiller

Life Sciences Faculty Research

Kalirin is a multidomain guanine nucleotide exchange factor (GEF) that activates Rho proteins, inducing cytoskeletal rearrangement in neurons. Although much is known about the effects of Kalirin on Rho GTPases and neuronal morphology, little is known about the association of Kalirin with the receptor/signaling systems that affect neuronal morphology. Our experiments demonstrate that Kalirin binds to and colocalizes with the TrkA neurotrophin receptor in neurons. In PC12 cells, inhibition of Kalirin expression using antisense RNA decreased nerve growth factor (NGF)-induced TrkA autophosphorylation and process extension. Kalirin overexpression potentiated neurotrophin-stimulated TrkA autophosphorylation and neurite outgrowth in PC12 cells at a low …

Investigating The Causes Of Low Birth Weight In Contrasting Ovine Paradigms., J M Wallace, Timothy Regnault, S W Limesand, W W Hay, R V Anthony

Paediatrics Publications

Intrauterine growth restriction (IUGR) still accounts for a large incidence of infant mortality and morbidity worldwide. Many of the circulatory and transport properties of the sheep placenta are similar to those of the human placenta and as such, the pregnant sheep offers an excellent model in which to study the development of IUGR. Two natural models of ovine IUGR are those of hyperthermic exposure during pregnancy, and adolescent overfeeding, also during pregnancy. Both models yield significantly reduced placental weights and an asymmetrically growth-restricted fetus, and display altered maternal hormone concentrations, indicative of an impaired trophoblast capacity. Additionally, impaired placental angiogenesis …

Effect Of Non-Metabolized Sweeteners On Health Parameters In Humans, Matthew Alan Leonhardt

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

The demand for functional foods is on the rise. These are food products that, besides providing energy and nutrients for life, provide additional health benefits. Xylitol, a five-carbon sugar alcohol, is a possible functional food, as well as a sugar replacement. The cost of xylitol has led manufacturers to add inulin, a nondigestible oligosaccharide, as an extender. Both xylitol and inulin have been suggested to provide added health benefits beyond being a reduced calorie replacement for sugar. We tested their impact on several human health parameters (fecal weight, fecal pH, fecal % moisture, blood lipids, blood glucose, and fecal micro …

Osler And The Infected Letter, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The spread of infectious agents through the mail has concerned public health officials for 5 centuries. The dissemination of anthrax spores in the US mail in 2001 was a recent example. In 1901, two medical journals reported outbreaks of smallpox presumably introduced by letters contaminated with variola viruses. The stability and infectivity of the smallpox virus are reviewed from both a historical (anecdotal) perspective and modern virologic studies. Bubonic plague was the contagious disease that led to quarantines as early as the 14th century in port cities in southern Europe. Later, smallpox, cholera, typhus, and yellow fever were recognized as …

Cart: An Hrs/Actinin-4/Berp/Myosin V Protein Complex Required For Efficient Receptor Recycling, Qing Yan, Wei Sun, Pekka Kujala, Yasmin Lotfi, Thomas A Vida, Andrew J Bean

Faculty, Staff and Student Publications

Altering the number of surface receptors can rapidly modulate cellular responses to extracellular signals. Some receptors, like the transferrin receptor (TfR), are constitutively internalized and recycled to the plasma membrane. Other receptors, like the epidermal growth factor receptor (EGFR), are internalized after ligand binding and then ultimately degraded in the lysosome. Routing internalized receptors to different destinations suggests that distinct molecular mechanisms may direct their movement. Here, we report that the endosome-associated protein hrs is a subunit of a protein complex containing actinin-4, BERP, and myosin V that is necessary for efficient TfR recycling but not for EGFR degradation. The …

Ocular Surface Epithelia Contain Abcg2-Dependent Side Population Cells Exhibiting Features Associated With Stem Cells., Murat T Budak, Onder S Alpdogan, Mingyuan Zhou, Robert M Lavker, M A Murat Akinci, J Mario Wolosin

Department of Medical Oncology Faculty Papers

When cell populations are incubated with the DNA-binding dye Hoechst 33342 and subjected to flow cytometry analysis for Hoechst 33342 emissions, active efflux of the dye by the ABCG2/BCRP1 transporter causes certain cells to appear as a segregated cohort, known as a side population (SP). Stem cells from several tissues have been shown to possess the SP phenotype. As the lack of specific surface markers has hindered the isolation and subsequent biochemical characterization of epithelial stem cells this study sought to determine the existence of SP cells and expression of ABCG2 in the epithelia of the ocular surface and evaluate …

Microsomal Prostaglandin E Synthase-1: The Inducible Synthase For Prostaglandin E2, Annaleise V. Sampey, Seetha Monrad, Leslie J. Crofford

Internal Medicine Faculty Publications

Microsomal prostaglandin E synthase-1 (mPGES-1) is an inducible enzyme that catalyzes the conversion of prostaglandin (PG)H2 to PGE2. Proinflammatory stimuli markedly increase levels of mPGES-1 expression both in vivo and in vitro. mPGES-1 knockout studies and animal models of inflammatory arthritis also provide a strong basis for the contribution of mPGES-1 in the increased local production of PGE2 observed in inflammatory arthritis. The focus of this article is to review some recent advances in our understanding of mechanisms specific to the regulation of inducible mPGES-1 in inflammatory arthritis.

Bench-To-Bedside Review: Rhabdomyolysis -- An Overview For Clinicians., Ana L Huerta-Alardín, Joseph Varon, Paul E Marik

Jefferson Hospital Staff Papers and Presentations

Rhabdomyolysis ranges from an asymptomatic illness with elevation in the creatine kinase level to a life-threatening condition associated with extreme elevations in creatine kinase, electrolyte imbalances, acute renal failure and disseminated intravascular coagulation. Muscular trauma is the most common cause of rhabdomyolysis. Less common causes include muscle enzyme deficiencies, electrolyte abnormalities, infectious causes, drugs, toxins and endocrinopathies. Weakness, myalgia and tea-colored urine are the main clinical manifestations. The most sensitive laboratory finding of muscle injury is an elevated plasma creatine kinase level. The management of patients with rhabdomyolysis includes early vigorous hydration.

A Short History Of Medical Dictionaries, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

No abstract provided.

Emergency Physicians' Practices And Attitudes Regarding Procedural Anaesthesia For Nasogastric Tube Insertion., G A. Juhl, Gregory P. Conners

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: To determine practice and attitudes of emergency physicians regarding procedural anaesthesia for nasogastric tube insertion (NGT).

METHODS: Survey of resident/attending emergency physicians working in a tertiary care medical centre.

RESULTS: Of 68 physicians, 46 responded: 98% believed that awake and alert patients find NGT insertion uncomfortable/painful; 93% used measures to reduce this, most commonly lubricant gel, topical anaesthetic spray, lidocaine gel, and distraction/use of a child life worker; 28% believed these provided adequate pain control and 37% believed they were inadequate. Topical anaesthetic spray, lidocaine gel, and nebulised/atomised anaesthetics were believed the most practical to administer and 44% actually …

Information-Seeking Behaviors Of Practitioners In A Primary Care Practice-Based Research Network (Pbrn), James E. Andrews, Kevin A. Pearce, Carol Ireson, Margaret M. Love

School of Information Faculty Publications

OBJECTIVE: The aim of this study was to examine the information-seeking behaviors (e.g., information resource usage patterns, access to types of sources and to medical libraries, and use of particular information technologies) of members in a primary care practice-based research network (PBRN) to inform future efforts supporting primary care practitioners in their daily care of patients.

METHODS: Every primary care practitioner who was a member of the Kentucky Ambulatory Network-including family practitioners, general practitioners, nurse practitioners, and physician assistants-was surveyed. The cross-sectional survey included twenty-six questions to investigate the information-seeking behavior of primary care practitioners.

RESULTS: The response rate was …

Learning To Like: A Role For Human Orbitofrontal Cortex In Conditioned Reward, Sylvia M L Cox, Alexandre Andrade, Ingrid Johnsrude

Brain and Mind Institute Researchers' Publications

A great deal of human behavior and motivation is based on the intrinsic emotional significance of rewarding or aversive events, as well as on the associations formed between such emotional events and concurrent environmental stimuli. Recent functional neuroimaging studies have implicated the ventral striatum, orbitofrontal cortex (OFC), and amygdala in the representation of reward values and/or in the anticipation of rewarding events. Here, we use functional magnetic resonance imaging to compare brain activation during the presentation of reward with that during presentation of (conditioned) stimuli that have been paired previously with reward. Specifically, we aimed to investigate conditioned reward in …

Automated Migration Analysis Based On Cell Texture: Method & Reliability, Jianfeng Qin, Thomas W. Chittenden, Ling Gao, Justin D D. Pearlman

Dartmouth Scholarship

Background: In this paper, we present and validate a way to measure automatically the extent of cell migration based on automated examination of a series of digital photographs. It was designed specifically to identify the impact of Second Hand Smoke (SHS) on endothelial cell migration but has broader applications. The analysis has two stages: (1) preprocessing of image texture, and (2) migration analysis.

Results: The output is a graphic overlay that indicates the front lines of cell migration superimposed on each original image, with automated reporting of the distance traversed vs. time. Expert preference compares to manual placement of leading …

Clinical Characteristics Of Individuals Using An Online Alcohol Evaluation Program., Daniel Z Lieberman

Psychiatry and Behavioral Sciences Faculty Publications

Access to treatment for substance abuse disorders is limited, and practical strategies are needed to expand opportunities for individuals to receive effective interventions. Automated or semi-automated treatments have shown promise in other disorders. Identifying the characteristics of patients who will be able to benefit from this unconventional approach will increase the likelihood of success. The current study examined 1,297 individuals using an online alcohol evaluation program. Subjects had high scores on the Alcohol Use Disorders Identification Test (AUDIT) and a substantial amount of ambivalence about the possible harm that their drinking caused, but they also had very low levels of …

A Contralateral Preference In The Lateral Occipital Area: Sensory And Attentional Mechanisms., Matthias Niemeier, Herbert C Goltz, Anil Kuchinad, Douglas B Tweed, Tutis Vilis

Brain and Mind Institute Researchers' Publications

Here we examined the level of the lateral occipital (LO) area within the processing stream of the ventral visual cortex. An important determinant of an area's level of processing is whether it codes visual elements on both sides of the visual field, as do higher visual areas, or prefers those in the contralateral visual field, as do early visual areas. The former would suggest that LO, on one side, combines bilateral visual elements into a whole, while the latter suggests that it codes only the parts of forms. We showed that LO has a relative preference for visual objects in …

Developing And Deploying A New Member Of The Dental Team: A Pediatric Oral Health Therapist, David A. Nash

Oral Health Science Faculty Publications

There are inadequate numbers of dentists able and willing to treat America's children, specifically children from low income and minority populations. This has led to the well-publicized disparities in oral health among children. In the early part of the 20^th century New Zealand faced a significant problem with oral disease among its children and introduced a School Dental Service, staffed by allied dental professionals with two years' training in caring for the teeth of children, "school dental nurses." A significant number of countries have adopted the model. This article reviews the history of attempts to develop such an approach …

The Meaning Of Computers To A Group Of Men Who Are Homeless., Kathleen Swenson Miller, Stacey Bunch-Harrison, Brett Brumbaugh, Rekha Sankaran Kutty, Kathleen Fitzgerald

Department of Occupational Therapy Faculty Papers

The purpose of this pilot study was to explore the experience with computers and the meaning of computers to a group of homeless men living in a long-term shelter. This descriptive exploratory study used semistructured interviews with seven men who had been given access to computers and had participated in individually tailored occupation based interventions through a Work Readiness Program. Three themes emerged from analyzing the interviews: access to computers, computers as a bridge to life-skill development, and changed self-perceptions as a result of connecting to technology. Because they lacked computer knowledge and feared failure, the majority of study participants …

Dynamic Changes In Mcl-1 Expression Regulate Macrophage Viability Or Commitment To Apoptosis During Bacterial Clearance, Helen M. Marriott, Colin D. Bingle, Robert C. Read, Karen E. Braley, Guido Kroemer, Paul G. Hellewell, Ruth W. Craig, Moira K.B. Whyte, David H. Dockrell

Dartmouth Scholarship

Macrophages are critical effectors of bacterial clearance and must retain viability, despite exposure to toxic bacterial products, until key antimicrobial functions are performed. Subsequently, host-mediated macrophage apoptosis aids resolution of infection. The ability of macrophages to make this transition from resistance to susceptibility to apoptosis is important for effective host innate immune responses. We investigated the role of Mcl-1, an essential regulator of macrophage lifespan, in this switch from viability to apoptosis, using the model of pneumococcal-associated macrophage apoptosis. Upon exposure to pneumococci, macrophages initially upregulate Mcl-1 protein and maintain viability for up to 14 hours. Subsequently, macrophages reduce expression …

Surgical Images: Soft Tissue. Incarcerated Gallbladder In A Parastomal Hernia., Shawn D. St Peter, Jacques Heppell

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Multiple Metabolic Hits Converge On Cd36 As Novel Mediator Of Tubular Epithelial Apoptosis In Diabetic Nephropathy., Katalin Susztak, Emilio Ciccone, Peter Mccue, Kumar Sharma, Erwin P Böttinger

Department of Medicine Faculty Papers

BACKGROUND: Diabetic nephropathy (DNP) is a common complication of type 1 and type 2 diabetes mellitus and the most common cause of kidney failure. While DNP manifests with albuminuria and diabetic glomerulopathy, its progression correlates best with tubular epithelial degeneration (TED) and interstitial fibrosis. However, mechanisms leading to TED in DNP remain poorly understood.

METHODS AND FINDINGS: We found that expression of scavenger receptor CD36 coincided with proximal tubular epithelial cell (PTEC) apoptosis and TED specifically in human DNP. High glucose stimulated cell surface expression of CD36 in PTECs. CD36 expression was necessary and sufficient to mediate PTEC apoptosis induced …

Yos1p Is A Novel Subunit Of The Yip1p–Yif1p Complex And Is Required For Transport Between The Endoplasmic Reticulum And The Golgi Complex, Matthew Heidtman, Catherine Z. Chen, Ruth N. Collins, Charles Barlowe

Dartmouth Scholarship

Yeast Yip1p is a member of a conserved family of transmembrane proteins that interact with Rab GTPases. Previous studies also have indicated a role for Yip1p in the biogenesis of endoplasmic reticulum (ER)-derived COPII transport vesicles. In this report, we describe the identification and characterization of the uncharacterized open reading frame YER074W-A as a novel multicopy suppressor of the thermosensitive yip1-4 strain. We have termed this gene Yip One Suppressor 1 (YOS1). Yos1p is essential for growth and for function of the secretory pathway; depletion or inactivation of Yos1p blocks transport between the ER and …

Tgf-Beta1 And Serum Both Stimulate Contraction But Differentially Affect Apoptosis In 3d Collagen Gels, Tetsu Kobayashi, Xiangde Liu, Hui Jung Kim, Tadashi Kohyama, Fu-Qiang Wen, Shinji Abe, Qiuhong Fang, Yun Kui Zhu, John R. Spurzem, Peter Bitterman, Stephen I. Rennard

Journal Articles: Pulmonary & Critical Care Med

Apoptosis of fibroblasts may be key for the removal of cells following repair processes. Contraction of three-dimensional collagen gels is a model of wound healing and remodeling. Here two potent inducers of contraction, TGF-beta1 and fetal calf serum (FCS) were evaluated for their effect on fibroblast apoptosis in contracting collagen gels. Human fetal lung fibroblasts were cultured in floating type I collagen gels, exposed to TGF-beta1 or FCS, and allowed to contract for 5 days. Apoptosis was evaluated using TUNEL and confirmed by DNA content profiling. Both TGF-beta1 and serum significantly augmented collagen gel contraction. TGF-beta1 also increased apoptosis assessed …

A Streptococcal Collagen-Like Protein Interacts With The Α 2 Β 1 Integrin And Induces Intracellular Signaling, Joseph O. Humtsoe, Jiyeun K. Kim, Yi Xu, Douglas R. Keene, Magnus Höök, Slawomir Lukomski, Kishore K. Wary

Faculty & Staff Scholarship

No abstract provided.