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Suppression Of Rhog Activity Is Mediated By A Syndecan 4–Synectin–Rhogdi1 Complex And Is Reversed By Pkcα In A Rac1 Activation Pathway, Arye Elfenbein, John M. Rhodes, Julia Meller, Martin A. Schwartz, Michiyuki Matsuda, Michael Simons Jul 2009

Suppression Of Rhog Activity Is Mediated By A Syndecan 4–Synectin–Rhogdi1 Complex And Is Reversed By Pkcα In A Rac1 Activation Pathway, Arye Elfenbein, John M. Rhodes, Julia Meller, Martin A. Schwartz, Michiyuki Matsuda, Michael Simons

Dartmouth Scholarship

Fibroblast growth factor 2 (FGF2) is a major regulator of developmental, pathological, and therapeutic angiogenesis. Its activity is partially mediated by binding to syndecan 4 (S4), a proteoglycan receptor. Angiogenesis requires polarized activation of the small guanosine triphosphatase Rac1, which involves localized dissociation from RhoGDI1 and association with the plasma membrane. Previous work has shown that genetic deletion of S4 or its adapter, synectin, leads to depolarized Rac activation, decreased endothelial migration, and other physiological defects. In this study, we show that Rac1 activation downstream of S4 is mediated by the RhoG activation pathway. RhoG is maintained in an inactive …


Perirhinal Cortex Contributes To Accuracy In Recognition Memory And Perceptual Discriminations., Edward B O'Neil, Anthony D Cate, Stefan Köhler Jul 2009

Perirhinal Cortex Contributes To Accuracy In Recognition Memory And Perceptual Discriminations., Edward B O'Neil, Anthony D Cate, Stefan Köhler

Brain and Mind Institute Researchers' Publications

The prevailing view of the medial temporal lobe (MTL) holds that its structures are dedicated to long-term declarative memory. Recent evidence challenges this position, suggesting that perirhinal cortex (PRc) in the MTL may also play a role in perceptual discriminations of stimuli with substantial visual feature overlap. Relevant neuropsychological findings in humans have been inconclusive, likely because studies have relied on patients with large and variable MTL lesions. Here, we conducted a functional magnetic resonance imaging study in healthy individuals to determine whether PRc shows a performance-related involvement in perceptual oddball judgments that is comparable to its established role in …


Craniofacial Anthropometric Norms Of Malaysian Indians, Wei Cheong Ngeow, S.T. Aljunid Jul 2009

Craniofacial Anthropometric Norms Of Malaysian Indians, Wei Cheong Ngeow, S.T. Aljunid

Research Publications (2006 to 2010)

Objective: This study was done to establish the craniofacial anthropometric norms of the young adult (18-25 years) Malaysian Indian. Materials and Methods: The study group consisted of convenient samples of 100 healthy volunteers, with equal number of female and male subjects who had no history of mixed racial-parentage. Twenty-two linear measurements were taken twice from 28 landmarks over six craniofacial regions. The methodology and evaluation of indices of the craniofacial region was adapted from Hajnis et al. Results: The minimum measurements are always contributed by the female Indian except for the nose height (n-sn), (left) eye fissure length (ex-en), upper …


Improving Clinical Quality Indicators Through Electronic Health Records: It Takes More Than Just A Reminder, Dean F Sittig, Jonathan M Teich, Jerome A Osheroff, Hardeep Singh Jul 2009

Improving Clinical Quality Indicators Through Electronic Health Records: It Takes More Than Just A Reminder, Dean F Sittig, Jonathan M Teich, Jerome A Osheroff, Hardeep Singh

Faculty, Staff and Student Publications

No abstract provided.


Treatment Of Monozygotic Twins With Obsessive Compulsive Disorder Using Cognitive Therapy And Exposure With Ritual Prevention, Michael P. Twohig, Maureen L. Whittal, Katherine A. Peterson Jun 2009

Treatment Of Monozygotic Twins With Obsessive Compulsive Disorder Using Cognitive Therapy And Exposure With Ritual Prevention, Michael P. Twohig, Maureen L. Whittal, Katherine A. Peterson

Psychology Faculty Publications

BACKGROUND: Assessment and treatment of cohabiting monozygotic (MZ) twins with obsessive compulsive disorder (OCD) is a possible challenge for clinical psychologists. AIMS: This study aims to present a detailed history of two sets of cohabiting MZ twins with OCD, and describe the adaption of cognitive behavior therapy in their treatments. METHOD: Two sets of cohabiting MZ twins completed a structured intake and the Yale Brown Obsessive Compulsive Scale as well as measures of depression, anxiety, a measure of obsessive beliefs, and thought action fusion. One set received cognitive behavior therapy and exposure with ritual prevention (ERP) simultaneously and the other …


Conservation Of The Glucan Phosphatase Laforin Is Linked To Rates Of Molecular Evolution And The Glucan Metabolism Of The Organism, Matthew S. Gentry, Rachel M. Pace Jun 2009

Conservation Of The Glucan Phosphatase Laforin Is Linked To Rates Of Molecular Evolution And The Glucan Metabolism Of The Organism, Matthew S. Gentry, Rachel M. Pace

Molecular and Cellular Biochemistry Faculty Publications

BACKGROUND: Lafora disease (LD) is a fatal autosomal recessive neurodegenerative disease. A hallmark of LD is cytoplasmic accumulation of insoluble glucans, called Lafora bodies (LBs). Mutations in the gene encoding the phosphatase laforin account for approximately 50% of LD cases, and this gene is conserved in all vertebrates. We recently demonstrated that laforin is the founding member of a unique class of phosphatases that dephosphorylate glucans.

RESULTS: Herein, we identify laforin orthologs in a protist and two invertebrate genomes, and report that laforin is absent in the vast majority of protozoan genomes and it is lacking in all other invertebrate …


The Role Of Demography And Markets In Determining Deforestation Rates Near Ranomafana National Park, Madagascar., Christopher P. Brooks, Christopher Holmes, Karen Kramer, Barry Barnett, Timothy H. Keitt Jun 2009

The Role Of Demography And Markets In Determining Deforestation Rates Near Ranomafana National Park, Madagascar., Christopher P. Brooks, Christopher Holmes, Karen Kramer, Barry Barnett, Timothy H. Keitt

CAS Publications

The highland forests of Madagascar are home to some of the world's most unique and diverse flora and fauna and to some of its poorest people. This juxtaposition of poverty and biodiversity is continually reinforced by rapid population growth, which results in increasing pressure on the remaining forest habitat in the highland region, and the biodiversity therein. Here we derive a mathematical expression for the subsistence of households to assess the role of markets and household demography on deforestation near Ranomafana National Park. In villages closest to urban rice markets, households were likely to clear less land than our model …


Epidemiology And Outcomes Of Candidemia In 2019 Patients: Data From The Prospective Antifungal Therapy Alliance Registry., David L Horn, Dionissios Neofytos, Elias J Anaissie, Jay A Fishman, William J Steinbach, Ali J Olyaei, Kieren A Marr, Michael A Pfaller, Chi-Hsing Chang, Karen M Webster Jun 2009

Epidemiology And Outcomes Of Candidemia In 2019 Patients: Data From The Prospective Antifungal Therapy Alliance Registry., David L Horn, Dionissios Neofytos, Elias J Anaissie, Jay A Fishman, William J Steinbach, Ali J Olyaei, Kieren A Marr, Michael A Pfaller, Chi-Hsing Chang, Karen M Webster

Jefferson Hospital Staff Papers and Presentations

BACKGROUND: Candidemia remains a major cause of morbidity and mortality in the health care setting, and the epidemiology of Candida infection is changing.

METHODS: Clinical data from patients with candidemia were extracted from the Prospective Antifungal Therapy (PATH) Alliance database, a comprehensive registry that collects information regarding invasive fungal infections. A total of 2019 patients, enrolled from 1 July 2004 through 5 March 2008, were identified. Data regarding the candidemia episode were analyzed, including the specific fungal species and patient survival at 12 weeks after diagnosis.

RESULTS: The incidence of candidemia caused by non-Candida albicans Candida species (54.4%) was higher …


Modulation Of Edna Release And Degradation Affects Staphylococcus Aureus Biofilm Maturation., Ethan E. Mann, Kelly C. Rice, Blaise R. Boles, Jennifer L. Endres, Dev Ranjit, Lakshmi Chandramohan, Laura H. Tsang, Mark S. Smeltzer, Alexander R. Horswill, Kenneth W. Bayles Jun 2009

Modulation Of Edna Release And Degradation Affects Staphylococcus Aureus Biofilm Maturation., Ethan E. Mann, Kelly C. Rice, Blaise R. Boles, Jennifer L. Endres, Dev Ranjit, Lakshmi Chandramohan, Laura H. Tsang, Mark S. Smeltzer, Alexander R. Horswill, Kenneth W. Bayles

Journal Articles: Pathology and Microbiology

Recent studies have demonstrated a role for Staphylococcus aureus cidA-mediated cell lysis and genomic DNA release in biofilm adherence. The current study extends these findings by examining both temporal and additional genetic factors involved in the control of genomic DNA release and degradation during biofilm maturation. Cell lysis and DNA release were found to be critical for biofilm attachment during the initial stages of development and the released DNA (eDNA) remained an important matrix component during biofilm maturation. This study also revealed that an lrgAB mutant exhibits increased biofilm adherence and matrix-associated eDNA consistent with its proposed role as an …


A Truncation Mutation In Tbc1d4 In A Family With Acanthosis Nigricans And Postprandial Hyperinsulinemia, Satya Dash, Hiroyuki Sano, Justin J. Rochford, Robert K. Semple Jun 2009

A Truncation Mutation In Tbc1d4 In A Family With Acanthosis Nigricans And Postprandial Hyperinsulinemia, Satya Dash, Hiroyuki Sano, Justin J. Rochford, Robert K. Semple

Dartmouth Scholarship

Tre-2, BUB2, CDC16, 1 domain family member 4 (TBC1D4) (AS160) is a Rab-GTPase activating protein implicated in insulin-stimulated glucose transporter 4 (GLUT4) translocation in adipocytes and myotubes. To determine whether loss-of-function mutations in TBC1D4 might impair GLUT4 translocation and cause insulin resistance in humans, we screened the coding regions of this gene in 156 severely insulin-resistant patients. A female presenting at age 11 years with acanthosis nigricans and extreme postprandial hyperinsulinemia was heterozygous for a premature stop mutation (R363X) in TBC1D4. After demonstrating reduced expression of wild-type TBC1D4 protein and expression of the truncated protein in lymphocytes from the proband, …


A Retrospective Claims Analysis Of Combination Therapy In The Treatment Of Adult Attention-Deficit/Hyperactivity Disorder (Adhd), Gerhardt M. Pohl, David L. Van Brunt, Wenyu Ye, William W. Stoops, Joseph A. Johnston Jun 2009

A Retrospective Claims Analysis Of Combination Therapy In The Treatment Of Adult Attention-Deficit/Hyperactivity Disorder (Adhd), Gerhardt M. Pohl, David L. Van Brunt, Wenyu Ye, William W. Stoops, Joseph A. Johnston

Behavioral Science Faculty Publications

BACKGROUND: Combination therapy in managing psychiatric disorders is not uncommon. While combination therapy has been documented for depression and schizophrenia, little is known about combination therapy practices in managing attention-deficit/hyperactivity disorder (ADHD). This study seeks to quantify the combination use of ADHD medications and to understand predictors of combination therapy.

METHODS: Prescription dispensing events were drawn from a U.S. national claims database including over 80 managed-care plans. Patients studied were age 18 or over with at least 1 medical claim with a diagnosis of ADHD (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 314.0), a pharmacy claim for …


Development And Validation Of An Index Of Musculoskeletal Functional Limitations, Jeffrey N. Katz, Elizabeth A. Wright, John A. Baron, Elena Losina Jun 2009

Development And Validation Of An Index Of Musculoskeletal Functional Limitations, Jeffrey N. Katz, Elizabeth A. Wright, John A. Baron, Elena Losina

Dartmouth Scholarship

While musculoskeletal problems are leading sources of disability, there has been little research on measuring the number of functionally limiting musculoskeletal problems for use as predictor of outcome in studies of chronic disease. This paper reports on the development and preliminary validation of a self administered musculoskeletal functional limitations index.


The Relationship Between Liver Fat Content And Unenhanced Computed Tomography, Karen Shoebotham Jun 2009

The Relationship Between Liver Fat Content And Unenhanced Computed Tomography, Karen Shoebotham

Yale Medicine Thesis Digital Library

The purpose of this study was to chart unenhanced CT liver and spleen attenuation data on patients with normal and fatty livers to demonstrate a relationship between liver fat content and attenuation on unenhanced CT using MR chemical shift imaging as a reference standard. Retrospective data was gathered on 116 patients from NYU Tisch Hospital who had undergone both an unenhanced CT and MR opposed-phase imaging of the liver within 2 months. MR fat fraction (MR FF) was calculated using signal decrease on in]phase and opposed]phase imaging, with a cutoff of 0.2 considered significant fatty infiltration. Three CT liver attenuation …


Outcomes In Patients With End-Stage Renal Disease And Colonic Diverticular Disease, Louis Salamone Jun 2009

Outcomes In Patients With End-Stage Renal Disease And Colonic Diverticular Disease, Louis Salamone

Yale Medicine Thesis Digital Library

Purpose: To evaluate clinical presentation and outcomes of patients with end-stage renal disease (ESRD) or renal transplantation and symptomatic colonic diverticular disease Methods: A retrospective review of all patients with the primary diagnosis of diverticulitis or diverticulosis and end-stage renal disease treated at Yale-New Haven Hospital from January 1, 1985 to December 31, 2005 was performed. Patient factors evaluated including age, gender, comorbidities, nature of ESRD, and immunosuppression if any, along with the diagnosis of diverticulosis or diverticulitis, complicated vs. uncomplicated and outcomes including morbidity, mortality and LOS. Patients were evaluated to determine predictors of poor outcome. Simple summary statistics …


Influence Of A Serotonin Transporter Promoter Polymorphism (5-Httlpr) On Corticolimbic Abnormalities In Bipolar Disorder An Integrated Genetics And Functional Mri Study, Maulik Shah Jun 2009

Influence Of A Serotonin Transporter Promoter Polymorphism (5-Httlpr) On Corticolimbic Abnormalities In Bipolar Disorder An Integrated Genetics And Functional Mri Study, Maulik Shah

Yale Medicine Thesis Digital Library

Bipolar disorder (BD) is associated with abnormalities of the subgenual anterior cingulate cortex (sgACC) and the amygdala, components of a corticolimbic neural system that subserves emotional regulation. The short s allele - as opposed to the long l allele - of a serotonin transporter promoter (5-HTTLPR) polymorphism is associated with more severe course features of BD and impaired functional connectivity between the sgACC and amygdala in healthy control (HC) individuals. This study tests the hypothesis that the s allele influences the dysfunction in the sgACC-amygdala neural system in BD. Twenty-six euthymic BD participants (17 s carriers, 9 ll) and 43 …


Failure To Replicate A Genetic Association May Provide Important Clues About Genetic Architecture, Casey S. Greene, Nadia M. Penrod, Scott M. Williams, Jason H. Moore Jun 2009

Failure To Replicate A Genetic Association May Provide Important Clues About Genetic Architecture, Casey S. Greene, Nadia M. Penrod, Scott M. Williams, Jason H. Moore

Dartmouth Scholarship

Replication has become the gold standard for assessing statistical results from genome-wide association studies. Unfortunately this replication requirement may cause real genetic effects to be missed. A real result can fail to replicate for numerous reasons including inadequate sample size or variability in phenotype definitions across independent samples. In genome-wide association studies the allele frequencies of polymorphisms may differ due to sampling error or population differences. We hypothesize that some statistically significant independent genetic effects may fail to replicate in an independent dataset when allele frequencies differ and the functional polymorphism interacts with one or more other functional polymorphisms. To …


Identifying Sleep Regulatory Genes Using A Drosophila Model Of Insomnia, Laurent Seugnet, Yasuko Suzuki, Matthew S. Thimgan, Jeffrey Donlea, Sarah I. Gimbel, Laura Gottschalk, Stephen P. Duntley, Paul J. Shaw Jun 2009

Identifying Sleep Regulatory Genes Using A Drosophila Model Of Insomnia, Laurent Seugnet, Yasuko Suzuki, Matthew S. Thimgan, Jeffrey Donlea, Sarah I. Gimbel, Laura Gottschalk, Stephen P. Duntley, Paul J. Shaw

Biological Sciences Faculty Research & Creative Works

Although it is widely accepted that sleep must serve an essential biological function, little is known about molecules that underlie sleep regulation. Given that insomnia is a common sleep disorder that disrupts the ability to initiate and maintain restorative sleep, a better understanding of its molecular underpinning may provide crucial insights into sleep regulatory processes. Thus, we created a line of flies using laboratory selection that share traits with human insomnia. After 60 generations, insomnia-like (ins-l) flies sleep 60 min a day, exhibit difficulty initiating sleep, difficulty maintaining sleep, and show evidence of daytime cognitive impairment. ins-l flies …


Strategic Management And Organizational Behavior In Dental Education: Reflections On Key Issues In An Environment Of Change., David G. Dunning, Timothy M. Durham, Brian M. Lange, Mert N. Aksu Jun 2009

Strategic Management And Organizational Behavior In Dental Education: Reflections On Key Issues In An Environment Of Change., David G. Dunning, Timothy M. Durham, Brian M. Lange, Mert N. Aksu

Journal Articles: College of Dentistry

With issues such as shrinking revenue, access to care, faculty workloads, and graying faculty, dental schools are faced with difficult challenges that fall to dental school deans to manage. Do dental school deans have the organizational skill sets and ethical frameworks necessary to address the challenges now facing dental schools? The purpose of this article is to pose questions and suggestions regarding some of the key issues in dental colleges today and to stimulate discussion in the dental community about needed changes in dental education.


Death Receptor 5 Internalization Is Required For Lysosomal Permeabilization By Trail In Malignant Liver Cell Lines., Yuko Akazawa, Justin L. Mott, Steven F. Bronk, Nathan W. Werneburg, Alisan Kahraman, Maria Eugenia Guicciardi, Xue Wei Meng, Shigeru Kohno, Vijay H. Shah, Scott H. Kaufmann, Mark A. Mcniven, Gregory J. Gores Jun 2009

Death Receptor 5 Internalization Is Required For Lysosomal Permeabilization By Trail In Malignant Liver Cell Lines., Yuko Akazawa, Justin L. Mott, Steven F. Bronk, Nathan W. Werneburg, Alisan Kahraman, Maria Eugenia Guicciardi, Xue Wei Meng, Shigeru Kohno, Vijay H. Shah, Scott H. Kaufmann, Mark A. Mcniven, Gregory J. Gores

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND & AIMS: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) cytotoxicity in hepatocellular carcinoma cells is mediated by lysosomal permeabilization. Our aims were to determine which TRAIL receptor, death receptor (DR) 4 or DR5, mediates lysosomal permeabilization and assess whether receptor endocytosis followed by trafficking to lysosomes contributes in this process.

METHODS: TRAIL ligand internalization in Huh-7 cells was examined by confocal microscopy using Flag-tagged TRAIL, whereas DR4- and DR5-enhanced green fluorescent protein internalization was assessed by total internal reflection microscopy. Clathrin-dependent endocytosis was inhibited by expressing dominant negative dynamin.

RESULTS: Although Huh-7 cells express both TRAIL receptors, short hairpin RNA …


Clinical And Translational Implications Of The Caveolin Gene Family: Lessons From Mouse Models And Human Genetic Disorders., Isabelle Mercier, Jean-Francois Jasmin, Stephanos Pavlides, Carlo Minetti, Neal Flomenberg, Richard G Pestell, Philippe G Frank, Federica Sotgia, Michael P Lisanti Jun 2009

Clinical And Translational Implications Of The Caveolin Gene Family: Lessons From Mouse Models And Human Genetic Disorders., Isabelle Mercier, Jean-Francois Jasmin, Stephanos Pavlides, Carlo Minetti, Neal Flomenberg, Richard G Pestell, Philippe G Frank, Federica Sotgia, Michael P Lisanti

Department of Stem Cell Biology and Regenerative Medicine Faculty Papers & Presentations

Here we review the clinical and translational implications of the caveolin gene family for understanding the pathogenesis of human diseases, including breast and prostate cancers, pulmonary hypertension, cardiomyopathy, diabetes, and muscular dystrophy. Detailed phenotypic analysis of caveolin knockout mice has served to highlight the crucial role of a caveolin deficiency in the pathogenesis of many human disease processes. Mutations in the human caveolin genes are associated with a number of established genetic disorders (such as breast cancer, lipodystrophy, muscular dystrophy, and cardiomyopathy), making the caveolins important and novel targets for drug development. The implementation of new strategies for caveolin replacement …


Cancer Information-Seeking Experiences: The Implications Of Hispanic Ethnicity And Spanish Language, Robin C. Vanderpool, Julie Kornfeld, Lila Finney Rutten, Linda Squiers Jun 2009

Cancer Information-Seeking Experiences: The Implications Of Hispanic Ethnicity And Spanish Language, Robin C. Vanderpool, Julie Kornfeld, Lila Finney Rutten, Linda Squiers

Health, Behavior & Society Faculty Publications

BACKGROUND: Strategies to support cancer information-seeking among Hispanics are needed.

METHODS: We analyzed data from the 2005 Health Information National Trends Survey (HINTS) to explore cancer information-seeking experiences among respondents according to ethnicity and language of interview.

RESULTS: Over 80% of Spanish-speaking Hispanics had never looked for cancer information. Compared to English-speaking respondents, Spanish-speaking Hispanics who sought cancer information indicated their search took a lot of effort (67%), was hard to understand (54%), and frustrating (42%). Spanish-speaking Hispanics noted minimal confidence in obtaining cancer information.

CONCLUSIONS: Language and cultural differences must be considered in the design, implementation, and dissemination of …


A Radiographic Study On The Visualization Of The Anterior Loop In Dentate Subjects Of Different Age Groups, Wei Cheong Ngeow, D.D. Dionysius, H. Ishak, P. Nambiar Jun 2009

A Radiographic Study On The Visualization Of The Anterior Loop In Dentate Subjects Of Different Age Groups, Wei Cheong Ngeow, D.D. Dionysius, H. Ishak, P. Nambiar

Research Publications (2006 to 2010)

The anterior loop is defined as where the mental neurovascular bundle crosses anterior to the mental foramen then doubles back to exit the mental foramen. It cannot be seen clinically but can be detected in 11-60 of panoramic radiographs. As this anatomical structure is important in determining the placement position of endosseous implants in the mandibular premolar region, a pilot study was undertaken to determine its visibility on dental panoramic radiographs in dentate subjects of various age groups. One or more anterior loops were visible in 39 (40.2) radiographs encompassing 66 sites (34.4). Interestingly, anterior loops were most commonly observed …


Revisiting Histidine-Dependent Acid Phosphatases: A Distinct Group Of Tyrosine Phosphatases., Suresh Veeramani, Ming-Shyue Lee, Ming-Fong Lin Jun 2009

Revisiting Histidine-Dependent Acid Phosphatases: A Distinct Group Of Tyrosine Phosphatases., Suresh Veeramani, Ming-Shyue Lee, Ming-Fong Lin

Journal Articles: Biochemistry & Molecular Biology

Although classical protein tyrosine phosphatase (PTP) superfamily members are cysteine-dependent, emerging evidence shows that many acid phosphatases (AcPs) function as histidine-dependent PTPs in vivo. These AcPs dephosphorylate phospho-tyrosine substrates intracellularly and could have roles in development and disease. In contrast to cysteine-dependent PTPs, they utilize histidine, rather than cysteine, for substrate dephosphorylation. Structural analyses reveal that active site histidine, but not cysteine, faces towards the substrate and functions as the phosphate acceptor. Nonetheless, during dephosphorylation, both histidine-dependent and cysteine-dependent PTPs use their active site arginine and aspartate for substrate binding and proton donation, respectively. Thus, we propose that they should …


It Is More Than Just A Reproductive Healthcare Visit: Experiences From An Adolescent Medicine Clinic, Marlene B. Huff, Kimberly K. Mcclanahan, Heather A. Brown, Hatim A. Omar Jun 2009

It Is More Than Just A Reproductive Healthcare Visit: Experiences From An Adolescent Medicine Clinic, Marlene B. Huff, Kimberly K. Mcclanahan, Heather A. Brown, Hatim A. Omar

Pediatrics Faculty Publications

The gynecologist may be the only physician that an adolescent depends on for primary and reproductive healthcare services. Because adolescent females often make personal healthcare decisions without the benefit of supportive parents/caregivers, it is imperative that the gynecologist understands the developmental issues encountered during this phase of life. The objective of this study is to identify cited complaints of adolescent females seeking reproductive care and, thus, provide gynecologists with needed information about the medical/mental health issues that may be encountered during routine reproductive care exams. The study group was adolescent females between the ages of 12 and 20 years old. …


Therapeutic Targeting Of Atp7b In Ovarian Carcinoma, Lingegowda S Mangala, Vesna Zuzel, Rosemarie Schmandt, Erik S Leshane, Jyotsna B Halder, Guillermo N Armaiz-Pena, Whitney A Spannuth, Takemi Tanaka, Mian M K Shahzad, Yvonne G Lin, Alpa M Nick, Christopher G Danes, Jeong-Won Lee, Nicholas B Jennings, Pablo E Vivas-Mejia, Judith K Wolf, Robert L Coleman, Zahid H Siddik, Gabriel Lopez-Berestein, Svetlana Lutsenko, Anil K Sood Jun 2009

Therapeutic Targeting Of Atp7b In Ovarian Carcinoma, Lingegowda S Mangala, Vesna Zuzel, Rosemarie Schmandt, Erik S Leshane, Jyotsna B Halder, Guillermo N Armaiz-Pena, Whitney A Spannuth, Takemi Tanaka, Mian M K Shahzad, Yvonne G Lin, Alpa M Nick, Christopher G Danes, Jeong-Won Lee, Nicholas B Jennings, Pablo E Vivas-Mejia, Judith K Wolf, Robert L Coleman, Zahid H Siddik, Gabriel Lopez-Berestein, Svetlana Lutsenko, Anil K Sood

Faculty, Staff and Student Publications

PURPOSE: Resistance to platinum chemotherapy remains a significant problem in ovarian carcinoma. Here, we examined the biological mechanisms and therapeutic potential of targeting a critical platinum resistance gene, ATP7B, using both in vitro and in vivo models.

EXPERIMENTAL DESIGN: Expression of ATP7A and ATP7B was examined in ovarian cancer cell lines by real-time reverse transcription-PCR and Western blot analysis. ATP7A and ATP7B gene silencing was achieved with targeted small interfering RNA (siRNA) and its effects on cell viability and DNA adduct formation were examined. For in vivo therapy experiments, siRNA was incorporated into the neutral nanoliposome 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC).

RESULTS: ATP7A …


Interaction With Lc8 Is Required For Pak1 Nuclear Import And Is Indispensable For Zebrafish Development., Christine M Lightcap, Gabor Kari, Luis E Arias-Romero, Jonathan Chernoff, Ulrich Rodeck, John C Williams Jun 2009

Interaction With Lc8 Is Required For Pak1 Nuclear Import And Is Indispensable For Zebrafish Development., Christine M Lightcap, Gabor Kari, Luis E Arias-Romero, Jonathan Chernoff, Ulrich Rodeck, John C Williams

Department of Biochemistry and Molecular Biology Faculty Papers

Pak1 (p21 activated kinase 1) is a serine/threonine kinase implicated in regulation of cell motility and survival and in malignant transformation of mammary epithelial cells. In addition, the dynein light chain, LC8, has been described to cooperate with Pak1 in malignant transformation of breast cancer cells. Pak1 itself may aid breast cancer development by phosphorylating nuclear proteins, including estrogen receptor alpha. Recently, we showed that the LC8 binding site on Pak1 is adjacent to the nuclear localization sequence (NLS) required for Pak1 nuclear import. Here, we demonstrate that the LC8-Pak1 interaction is necessary for epidermal growth factor (EGF)-induced nuclear import …


Decorin Is A Novel Antagonistic Ligand Of The Met Receptor., Silvia Goldoni, Ashley Humphries, Alexander Nyström, Sampurna Sattar, Rick T Owens, David J Mcquillan, Keith Ireton, Renato V Iozzo May 2009

Decorin Is A Novel Antagonistic Ligand Of The Met Receptor., Silvia Goldoni, Ashley Humphries, Alexander Nyström, Sampurna Sattar, Rick T Owens, David J Mcquillan, Keith Ireton, Renato V Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Decorin, a member of the small leucine-rich proteoglycan gene family, impedes tumor cell growth by down-regulating the epidermal growth factor receptor. Decorin has a complex binding repertoire, thus, we predicted that decorin would modulate the bioactivity of other tyrosine kinase receptors. We discovered that decorin binds directly and with high affinity (K(d) = approximately 1.5 nM) to Met, the receptor for hepatocyte growth factor (HGF). Binding of decorin to Met is efficiently displaced by HGF and less efficiently by internalin B, a bacterial Met ligand. Interaction of decorin with Met induces transient receptor activation, recruitment of the E3 ubiquitin ligase …


Hiv Policy: The Path Forward--A Joint Position Paper Of The Hiv Medicine Association Of The Infectious Diseases Society Of America And The American College Of Physicians., Christine Lubinski, Judith Aberg, Arlene D Bardeguez, Richard Elion, Patricia Emmanuel, Daniel Kuritzkes, Michael Saag, Kathleen E Squires, Andrea Weddle, Jennifer Rainey, M Renee Zerehi, J Fred Ralston, David A Fleming, David Bronson, Molly Cooke, Charles Cutler, Yul Ejnes, Robert Gluckman, Mark Liebow, Kenneth Musana, Mark E Mayer, Mark W Purtle, P Preston Reynolds, Lavanya Viswanathan, Kevin B Weiss, Baligh Yehia May 2009

Hiv Policy: The Path Forward--A Joint Position Paper Of The Hiv Medicine Association Of The Infectious Diseases Society Of America And The American College Of Physicians., Christine Lubinski, Judith Aberg, Arlene D Bardeguez, Richard Elion, Patricia Emmanuel, Daniel Kuritzkes, Michael Saag, Kathleen E Squires, Andrea Weddle, Jennifer Rainey, M Renee Zerehi, J Fred Ralston, David A Fleming, David Bronson, Molly Cooke, Charles Cutler, Yul Ejnes, Robert Gluckman, Mark Liebow, Kenneth Musana, Mark E Mayer, Mark W Purtle, P Preston Reynolds, Lavanya Viswanathan, Kevin B Weiss, Baligh Yehia

Department of Medicine Faculty Papers

Executive Summary

The American College of Physicians (ACP) and the Infectious Diseases Society of America (IDSA) have jointly published 3 policy statements on AIDS, the first in 1986 [1], the second in 1988 [2], and the third in 1994 [3]. In 2001, the IDSA created the HIV Medicine Association (HIVMA), and this updated policy paper is a collaboration between the ACP and the HIVMA of the IDSA. Since the last statement, many new developments call for the need to reexamine and update our policies relating to HIV infection. First, there have been major advances …


A Gene Expression Predictor Of Response To Egfr-Targeted Therapy Stratifies Progression-Free Survival To Cetuximab In Kras Wild-Type Metastatic Colorectal Cancer, Justin M. Balko, Esther P. Black May 2009

A Gene Expression Predictor Of Response To Egfr-Targeted Therapy Stratifies Progression-Free Survival To Cetuximab In Kras Wild-Type Metastatic Colorectal Cancer, Justin M. Balko, Esther P. Black

Pharmaceutical Sciences Faculty Publications

BACKGROUND: The anti-EGFR monoclonal antibody cetuximab is used in metastatic colorectal cancer (CRC), and predicting responsive patients garners great interest, due to the high cost of therapy. Mutations in the KRAS gene occur in ~40% of CRC and are a negative predictor of response to cetuximab. However, many KRAS-wildtype patients do not benefit from cetuximab. We previously published a gene expression predictor of sensitivity to erlotinib, an EGFR inhibitor. The purpose of this study was to determine if this predictor could identify KRAS-wildtype CRC patients who will benefit from cetuximab therapy.

METHODS: Microarray data from 80 metastatic CRC patients subsequently …


Memory Functioning In Developmental Dyslexia: An Analysis Using Two Clinical Memory Measures., Michelle Y. Kibby May 2009

Memory Functioning In Developmental Dyslexia: An Analysis Using Two Clinical Memory Measures., Michelle Y. Kibby

Publications

The goals of this project were threefold: to determine the nature of the memory deficit in children/adolescents with dyslexia, to utilize clinical memory measures in this endeavor, and to determine the extent to which semantic short-term memory (STM) is related to basic reading performance. Two studies were conducted using different samples, one incorporating the Wide Range Assessment of Memory and Learning and the other incorporating the California Verbal Learning Test-Children's Version. Results suggest that phonological STM is deficient in children with dyslexia, but semantic STM and visual-spatial STM are intact. Long-term memory (LTM) for both visual and verbal material also …