Digital Commons Network^™

Preventing Cardiovascular Disease In Kentucky: Epidemiology, Trends, And Strategies For The Future, Sarah Sartini Rugg, Alison L. Bailey, Steven R. Browning

Internal Medicine Faculty Publications

Cardiovascular disease (CVD) is the leading cause of death in the United States despite dramatic improvements in the treatment of heart disease in recent years. Kentucky leads the nation in the prevalence of several individual risk factors for cardiovascular disease, the prevalence of multiple risk factors, and in cardiovascular mortality. While trends in the prevalence of some of these cardiac risk factors have shown improvement, others have remained unchanged or have worsened. The increased prevalence of obesity and diabetes, especially among young persons, is one of the most worrisome trends. The prevalence of smoking in Kentucky remains high, and has …

Ly2109761, A Novel Transforming Growth Factor Beta Receptor Type I And Type Ii Dual Inhibitor, As A Therapeutic Approach To Suppressing Pancreatic Cancer Metastasis, Davide Melisi, Satoshi Ishiyama, Guido M Sclabas, Jason B Fleming, Qianghua Xia, Giampaolo Tortora, James L Abbruzzese, Paul J Chiao

Faculty, Staff and Student Publications

Most pancreatic cancer patients present with inoperable disease or develop metastases after surgery. Conventional therapies are usually ineffective in treating metastatic disease. It is evident that novel therapies remain to be developed. Transforming growth factor beta (TGF-beta) plays a key role in cancer metastasis, signaling through the TGF-beta type I/II receptors (TbetaRI/II). We hypothesized that targeting TbetaRI/II kinase activity with the novel inhibitor LY2109761 would suppress pancreatic cancer metastatic processes. The effect of LY2109761 has been evaluated on soft agar growth, migration, invasion using a fibroblast coculture model, and detachment-induced apoptosis (anoikis) by Annexin V flow cytometric analysis. The efficacy …

Drug Metabolism In Human Brain: High Levels Of Cytochrome P4503a43 In Brain And Metabolism Of Anti-Anxiety Drug Alprazolam To Its Active Metabolite, Varsha Agarwal, Reddy P. Kommaddi, Khader Valli, Daniel Ryder, Thomas M. Hyde, Joel E. Kleinman, Henry W. Strobel, Vijayalakshmi Ravindranath

Faculty, Staff and Student Publications

Cytochrome P450 (P450) is a super-family of drug metabolizing enzymes. P450 enzymes have dual function; they can metabolize drugs to pharmacologically inactive metabolites facilitating their excretion or biotransform them to pharmacologically active metabolites which may have longer half-life than the parent drug. The variable pharmacological response to psychoactive drugs typically seen in population groups is often not accountable by considering dissimilarities in hepatic metabolism. Metabolism in brain specific nuclei may play a role in pharmacological modulation of drugs acting on the CNS and help explain some of the diverse response to these drugs seen in patient population. P450 enzymes are …

Retinal Pigment Epithelial Tears After Intravitreal Bevacizumab Injection For Exudative Age-Related Macular Degeneration., Sunir Garg, Roy Brod, David Kim, R Gary Lane, Joseph Maguire, David Fischer

Wills Eye Hospital Papers

PURPOSE: To determine the incidence of and the risk factors for the development of retinal pigment epithelial (RPE) tears after intravitreal bevacizumab (Avastin) injection for the treatment of exudative age-related macular degeneration (AMD).

METHODS: A retrospective, multicentre, consecutive interventional case series of all patients with subfoveal exudative AMD treated with intravitreal bevacizumab between August 2005 and April 2007. The main outcome measures were pre- and post-RPE tear visual acuity and choroidal neovascular membrane lesion types, incidence of tears and time from first injection until development of the tear.

RESULTS: A total of 920 eyes with exudative AMD were treated with …

The Effect Of Dexmedetomidine On The Mini-Cog Score And High-Mobility Group Box 1 Levels In Elderly Patients With Postoperative Neurocognitive Disorders Undergoing Orthopedic Surgery, Joan M Mastrobattista, Mark A Klebanoff, J Christopher Carey, John C Hauth, Cora A Macpherson, J Ernest, Margaret Cotroneo, Kenneth J Leveno, Ronald Wapner, Michael Varner, Jay D Iams, Atef Moawad, Baha M Sibai, Menachem Miodovnik, Mitchell Dombrowski, Mary J O'Sullivan, J Peter Vandorsten, Oded Langer

Faculty, Staff and Student Publications

Our objective was to determine the effect of body mass index (BMI) on response to bacterial vaginosis (BV) treatment. A secondary analysis was conducted of two multicenter trials of therapy for BV and TRICHOMONAS VAGINALIS. Gravida were screened for BV between 8 and 22 weeks and randomized between 16 and 23 weeks to metronidazole or placebo. Of 1497 gravida with asymptomatic BV and preconceptional BMI, 738 were randomized to metronidazole; BMI was divided into categories: < 25, 25 to 29.9, and > or = 30. Rates of BV persistence at follow-up were compared using the Mantel-Haenszel chi square. Multiple logistic regression was used to evaluate the effect …

Abstracts In High Profile Journals Often Fail To Report Harm, Enrique Bernal-Delgado, Elliot S. Fisher

Dartmouth Scholarship

To describe how frequently harm is reported in the abstract of high impact factor medical journals. We carried out a blinded structured review of a random sample of 363 Randomised Controlled Trials (RCTs) carried out on human beings, and published in high impact factor medical journals in 2003. Main endpoint: 1) Proportion of articles reporting harm in the abstract; and 2) Proportion of articles that reported harm in the abstract when harm was reported in the main body of the article. Analysis: Corrected Prevalence Ratio (cPR) and its exact confidence interval were calculated. Non-conditional logistic regression was used.

The Use And Safety Of Vascular Occlusion Techniques: A Survey Of Practicing Surgeons, Ryan Kelly

Yale Medicine Thesis Digital Library

Vascular occlusion techniques can be divided into two categories ¡V transfixion and non-transfixion. Transfixion techniques are defined by the passage of suture material or staples through the vascular tissue. Non-transfixion techniques are defined as suture, metal, or polymer material placed solely around the vascular tissue. The purpose of this study was to survey surgeons in various specialties to determine which vascular control technique they believe is safest and most appropriate to manage medium-sized arteries 6-10mm in diameter. A survey was distributed to surgeons in the following specialties: general surgery, urology, thoracic surgery, vascular surgery, obstetrics and gynecology, and colon and …

A Technological Approach To Reaching A Hidden Population Of Problem Drinkers., Daniel Z Lieberman, Suena W Huang

Psychiatry and Behavioral Sciences Faculty Publications

OBJECTIVE: The most common obstacle to the treatment of individuals with drinking problems is that most do not seek treatment. This study compared a group of treatment-seeking patients with users of an alcohol-evaluation Web site to determine whether an Internet application could reach a population of problem drinkers who are distinct from those served by currently available forms of care.

METHODS: An open-source application was developed that was modeled on the Drinker's Check-Up, which has been shown to increase motivation for behavior change while presenting itself as a nonthreatening evaluation. To recruit non-treatment seekers, the program was offered as a …

Verb Generation In Children With Spina Bifida, Maureen Dennis, Derryn Jewell, Ross Hetherington, Christine Burton, Michael E. Brandt, Susan E. Blaser, Jack M Fletcher

Faculty, Staff and Student Publications

We investigated verb generation in children with spina bifida meningomyelocele (SBM; n = 55) and in typically developing controls (n = 32). Participants completed 6 blocks (40 trials each) of a task requiring them to produce a semantically related verb in response to a target noun and an additional 40 trials on which they were simply required to read target nouns aloud. After controlling for reading response time, groups did not differ significantly in verb generation response time or learning. Children with SBM produced more non-verb errors than controls and tended to repeat their mistakes over blocks. Verb generation performance …

Computational Models Of Tandem Src Homology 2 Domain Interactions And Application To Phosphoinositide 3-Kinase, Dipak Barua, James R. Faeder, Jason M. Haugh

Chemical and Biochemical Engineering Faculty Research & Creative Works

Intracellular signal transduction proteins typically utilize multiple interaction domains for proper targeting, and thus a broad diversity of distinct signaling complexes may be assembled. Considering the coordination of only two such domains, as in tandem Src homology 2 (SH2) domain constructs, gives rise to a kinetic scheme that is not adequately described by simple models used routinely to interpret in vitro binding measurements. To analyze the interactions between tandem SH2 domains and bisphosphorylated peptides, we formulated detailed kinetic models and applied them to the phosphoinositide 3-kinase p85 regulatory subunit/platelet-derived growth factor β-receptor system. Data for this system from different in …

Using Built Environment Characteristics To Predict Walking For Exercise, Gina S. Lovasi, Anne V. Moudon, Amber L. Pearson, Philip M. Hurvitz, Eric B. Larson, David S. Siscovick, Ethan M. Berke

Dartmouth Scholarship

Environments conducive to walking may help people avoid sedentary lifestyles and associated diseases. Recent studies developed walkability models combining several built environment characteristics to optimally predict walking. Developing and testing such models with the same data could lead to overestimating one's ability to predict walking in an independent sample of the population. More accurate estimates of model fit can be obtained by splitting a single study population into training and validation sets (holdout approach) or through developing and evaluating models in different populations. We used these two approaches to test whether built environment characteristics near the home predict walking for …

Sputum Microscopy For The Diagnosis Of Hiv-Associated Pulmonary Tuberculosis In Tanzania, Mecky Matee, Lillian Mtei, Tarja Lounasvaara, Wendy Wieland-Alter, Richard Waddell, Johnson Lyimo, Muhammed Bakari, Kisali Pallangyo, C Fordham Von Reyn

Dartmouth Scholarship

Background:

In many resource poor settings only sputum microscopy is employed for the diagnosis of HIV-associated pulmonary tuberculosis; sputum culture may not be available.

Methods:

We determined the diagnostic accuracy of sputum microscopy for active case finding of HIV-associated pulmonary tuberculosis using TB culture as the reference standard.

Results:

2216 potential subjects screened for a TB vaccine trial submitted 9454 expectorated sputum specimens: 212 (2.2%) were sputum culture positive for Mycobacterium tuberculosis (MTB), 31 (0.3%) for non-tuberculous mycobacteria, and 79 (0.8%) were contaminated. The overall sensitivity of sputum microscopy was 61.8% (131/212) and specificity 99.7% (9108/9132). Sputum microscopy sensitivity varied …

Sp1 Up-Regulates Camp-Response-Element-Binding Protein Expression During Retinoic Acid-Induced Mucous Differentiation Of Normal Human Bronchial Epithelial Cells, Jeong Soo Hong, Seung-Wook Kim, Ja Seok Koo

Faculty, Staff and Student Publications

CREB [CRE (cAMP-response element)-binding protein] is an important transcription factor that is differentially regulated in cells of various types. We recently reported that RA (retinoic acid) rapidly activates CREB without using RARs (RA receptors) or RXRs (retinoid X receptors) in NHTBE cells (normal human tracheobronchial epithelial cells). However, little is known about the role of RA in the physiological regulation of CREB expression in the early mucous differentiation of NHTBE cells. In the present study, we report that RA up-regulates CREB gene expression and that, using 5'-serial deletion promoter analysis and mutagenesis analyses, two Sp1 (specificity protein 1)-binding sites located …

Switching Language Switches Mind: Linguistic Effects On Developmental Neural Bases Of ‘Theory Of Mind’, Chiyoko Kobayashi, Gary H. Glover, Elise Temple

Dartmouth Scholarship

Theory of mind (ToM)—our ability to predict behaviors of others in terms of their underlying intentions—has been examined through false-belief (FB) tasks. We studied 12 Japanese early bilingual children (8−12 years of age) and 16 late bilingual adults (18−40 years of age) with FB tasks in Japanese [first language (L1)] and English [second language (L2)], using fMRI. Children recruited more brain regions than adults for processing ToM tasks in both languages. Moreover, children showed an overlap in brain activity between the L1 and L2 ToM conditions in the medial prefrontal cortex (mPFC). Adults did not show such a convergent activity …

Celecoxib Concentration Predicts Decrease In Prostaglandin E2 Concentrations In Nipple Aspirate Fluid From High Risk Women, Edward R. Sauter, Wenyi Qin, John E. Hewett, Rachel L. Ruhlen, John T. Flynn, George Rottinghaus, Yin-Chieh Chen

Department of Molecular Physiology and Biophysics Faculty Papers

BACKGROUND: Epidemiologic studies suggest that long term low dose celecoxib use significantly lowers breast cancer risk. We previously demonstrated that 400 mg celecoxib taken twice daily for 2 weeks lowered circulating plasma and breast nipple aspirate fluid (NAF) prostaglandin (PG)E2 concentrations in post- but not premenopausal high risk women. We hypothesized that circulating concentrations of celecoxib influenced PGE2 response, and that plasma levels of the drug are influenced by menopausal status. To address these hypotheses, the aims of the study were to determine: 1) if circulating plasma concentrations of celecoxib correlated with the change in plasma or NAF PGE2 concentrations …

Bradykinin Type 2 Receptor Be1 Genotype Influences Bradykinin-Dependent Vasodilation During Angiotensin-Converting Enzyme Inhibition, Gary Van Guilder, Mias Pretorius, James M Luther, J Brian Byrd, Kevin Hill, James V Gainer, Nancy J Brown

Health and Nutritional Sciences Faculty Publications

To test the hypothesis that the bradykinin receptor 2 (BDKRB2) BE1+9/-9 polymorphism affects vascular responses to bradykinin, we measured the effect of intra-arterial bradykinin on forearm blood flow and tissue-type plasminogen activator (t-PA) release in 89 normotensive, nonsmoking, white American subjects in whom degradation of bradykinin was blocked by enalaprilat. BE1 genotype frequencies were +9/+9:+9/-9:-9/-9=19:42:28. BE1 genotype was associated with systolic blood pressure (121.4+/-2.8, 113.8+/-1.8, and 110.6+/-1.8 mm Hg in +9/+9, +9/-9, and -9/-9 groups, respectively; P=0.007). In the absence of enalaprilat, bradykinin-stimulated forearm blood flow, forearm vascular resistance, and net t-PA release were similar among genotype groups. Enalaprilat increased …

Antidepressant Prescribing Practices For The Treatment Of Children And Adolescents., Supriya K. Bhatia, Amy J. Rezac-Elgohary, Benedetto Vitiello, Michael A. Sitorius, Bruce A. Buehler, Christopher J. Kratochvil

Journal Articles: Psychiatry

OBJECTIVE: This study evaluates pediatric antidepressant prescribing practices of Nebraska clinicians.

METHODS: Surveys were sent in July, 2005, to 1,521 prescribing clinicians throughout Nebraska to assess pediatric antidepressant use along with any practice changes following the U.S. Food and Drug Administration (FDA) "black box" warning issued in October, 2004.

RESULTS: Over half (n = 866) of the clinicians responded to the survey, of which 96.8% reported awareness of the FDA "black box" warning. Of the respondents, 76.9% (n = 666) were prescribing antidepressants to children and/or adolescents. Clinicians reported decreased prescribing frequency for both children (15.5%) and adolescents (36.6%), with …

Current Application Of Thoracoscopy In Children., Kuojen Tsao, Shawn D. St Peter, Susan W. Sharp, Abhilash Nair, Walter S. Andrews, Ronald J. Sharp, Charles L. Snyder, Daniel J. Ostlie, G W. Holcomb Iii

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The safety and efficacy of thoracoscopy for thoracic lesions and conditions in children is evolving. Our experience with thoracoscopy has expanded in recent years. Therefore, we reviewed our most recent 7-year experience to examine the current applications for thoracoscopy in children.

METHODS: A retrospective review of all patients undergoing a thoracoscopic operation at Children's Mercy Hospital (Kansas City, MO) between January 1, 2000, and June 18, 2007, was performed. Data points reviewed included patient demographics, type of operation, final diagnosis, complications, and recovery.

RESULTS: During the study period, 230 children underwent 231 thoracoscopic procedures. The mean age was 9.6 …

Focal White Matter Changes In Spasmodic Dysphonia: A Combined Diffusion Tensor Imaging And Neuropathological Study, Kristina Simonyan, Fernanda Tovar-Moll, John Ostuni, Mark Hallett, Victor F Kalasinsky, Michael R Lewin-Smith, Elisabeth J Rushing, Alexander O Vortmeyer, Christy L Ludlow

Faculty, Staff and Student Publications

Spasmodic dysphonia is a neurological disorder characterized by involuntary spasms in the laryngeal muscles during speech production. Although the clinical symptoms are well characterized, the pathophysiology of this voice disorder is unknown. We describe here, for the first time to our knowledge, disorder-specific brain abnormalities in these patients as determined by a combined approach of diffusion tensor imaging (DTI) and postmortem histopathology. We used DTI to identify brain changes and to target those brain regions for neuropathological examination. DTI showed right-sided decrease of fractional anisotropy in the genu of the internal capsule and bilateral increase of overall water diffusivity in …

Abeta42 Mutants With Different Aggregation Profiles Induce Distinct Pathologies In Drosophila., Koichi Iijima, Hsueh-Cheng Chiang, Stephen A Hearn, Inessa Hakker, Anthony Gatt, Christopher Shenton, Linda Granger, Amy Leung, Kanae Iijima-Ando, Yi Zhong

Department of Biochemistry and Molecular Biology Faculty Papers

Aggregation of the amyloid-beta-42 (Abeta42) peptide in the brain parenchyma is a pathological hallmark of Alzheimer's disease (AD), and the prevention of Abeta aggregation has been proposed as a therapeutic intervention in AD. However, recent reports indicate that Abeta can form several different prefibrillar and fibrillar aggregates and that each aggregate may confer different pathogenic effects, suggesting that manipulation of Abeta42 aggregation may not only quantitatively but also qualitatively modify brain pathology. Here, we compare the pathogenicity of human Abeta42 mutants with differing tendencies to aggregate. We examined the aggregation-prone, EOFAD-related Arctic mutation (Abeta42Arc) and an artificial mutation (Abeta42art) that …

Bifidobacteria In Feces And Environmental Waters, Regina Lamendella, Jorge W. Santo Domingo, Catherine A. Kelty, Daniel B. Oerther

Civil, Architectural and Environmental Engineering Faculty Research & Creative Works

Bifidobacteria have been recommended as potential indicators of human fecal pollution in surface waters even though very little is known about their presence in nonhuman fecal sources. The objective of this research was to shed light on the occurrence and molecular diversity of this fecal indicator group in different animals and environmental waters. Genus- and species-specific 16S rRNA gene PCR assays were used to study the presence of bifidobacteria among 269 fecal DNA extracts from 32 different animals. Twelve samples from three wastewater treatment plants and 34 water samples from two fecally impacted watersheds were also tested. The species-specific assays …

Arsenic As An Endocrine Disruptor: Arsenic Disrupts Retinoic Acid Receptor–And Thyroid Hormone Receptor–Mediated Gene Regulation And Thyroid Hormone–Mediated Amphibian Tail Metamorphosis, Jennifer C. Davey, Athena P. Nomikos, Manida Wungjiranirun, Jenna R. Sherman, Liam Ingram, Cavus Batki, Jean P. Lariviere, Joshua W. Hamilton

Dartmouth Scholarship

Background:

Chronic exposure to excess arsenic in drinking water has been strongly associated with increased risks of multiple cancers, diabetes, heart disease, and reproductive and developmental problems in humans. We previously demonstrated that As, a potent endocrine disruptor at low, environmentally relevant levels, alters steroid signaling at the level of receptor-mediated gene regulation for all five steroid receptors.

Objectives:

The goal of this study was to determine whether As can also disrupt gene regulation via the retinoic acid (RA) receptor (RAR) and/or the thyroid hormone (TH) receptor (TR) and whether these effects are similar to previously observed effects on steroid …

Dissociation Predicts Later Attention Problems In Sexually Abused Children, Julie B Kaplow, Erin Hall, Karestan C Koenen, Kenneth A Dodge, Lisa Amaya-Jackson

Faculty, Staff and Students Publications

OBJECTIVE: The goals of this research are to develop and test a prospective model of attention problems in sexually abused children that includes fixed variables (e.g., gender), trauma, and disclosure-related pathways.

METHODS: At Time 1, fixed variables, trauma variables, and stress reactions upon disclosure were assessed in 156 children aged 8-13 years. At the Time 2 follow-up (8-36 months following the initial interview), 56 of the children were assessed for attention problems.

RESULTS: A path analysis involving a series of hierarchically nested, ordinary least squares multiple regression analyses indicated two direct paths to attention problems including the child's relationship to …

The Expression Of Microrna Mir-107 Decreases Early In Alzheimer's Disease And May Accelerate Disease Progression Through Regulation Of Β-Site Amyloid Precursor Protein-Cleaving Enzyme 1, Wang-Xia Wang, Bernard W. Rajeev, Arnold J. Stromberg, Na Ren, Guiliang Tang, Qingwei Huang, Isidore Rigoutsos, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

MicroRNAs (miRNAs) are small regulatory RNAs that participate in posttranscriptional gene regulation in a sequence-specific manner. However, little is understood about the role(s) of miRNAs in Alzheimer's disease (AD). We used miRNA expression microarrays on RNA extracted from human brain tissue from the University of Kentucky Alzheimer's Disease Center Brain Bank with near-optimal clinicopathological correlation. Cases were separated into four groups: elderly nondemented with negligible AD-type pathology, nondemented with incipient AD pathology, mild cognitive impairment (MCI) with moderate AD pathology, and AD. Among the AD-related miRNA expression changes, miR-107 was exceptional because miR-107 levels decreased significantly even in patients with …

Genome-Wide Expression Profiling Reveals Transcriptomic Variation And Perturbed Gene Networks In Androgen-Dependent And Androgen-Independent Prostate Cancer Cells., Ajay P. Singh, Sangeeta Bafna, Kunal Chaudhary, Ganesh Venkatraman, Lynette Smith, James D. Eudy, Sonny L. Johansson, Ming-Fong Lin, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Previously, we have developed a unique in vitro LNCaP cell model, which includes androgen-dependent (LNCaP-C33), androgen-independent (LNCaP-C81) and an intermediate phenotype (LNCaP-C51) cell lines resembling the stages of prostate cancer progression to hormone independence. This model is advantageous in overcoming the heterogeneity associated with the prostate cancer up to a certain extent. We characterized and compared the gene expression profiles in LNCaP-C33 (androgen-dependent) and LNCaP-C81 (androgen-independent) cells using Affymetrix GeneChip array analyses. Multiple genes were identified exhibiting differential expression during androgen-independent progression. Among the important genes upregulated in androgen-independent cells were PCDH7, TPTE, TSPY, EPHA3, HGF, MET, EGF, TEM8, etc., …

A Neuroanatomically Grounded Hebbian-Learning Model Of Attention-Language Interactions In The Human Brain., Max Garagnani, Thomas Wennekers, Friedemann Pulvermüller

School of Engineering, Computing and Mathematics

Meaningful familiar stimuli and senseless unknown materials lead to different patterns of brain activation. A late major neurophysiological response indexing 'sense' is the negative component of event-related potential peaking at around 400 ms (N400), an event-related potential that emerges in attention-demanding tasks and is larger for senseless materials (e.g. meaningless pseudowords) than for matched meaningful stimuli (words). However, the mismatch negativity (latency 100-250 ms), an early automatic brain response elicited under distraction, is larger to words than to pseudowords, thus exhibiting the opposite pattern to that seen for the N400. So far, no theoretical account has been able to reconcile …

Women's Colposcopy Experience And Preferences: A Mixed Methods Study., Dawn R. Swancutt, Sheila M. Greenfield, Sue Wilson

Peninsula Medical School

BACKGROUND: The colposcopy service is a key component in the UK Cervical Screening Programme. Over 120,000 women are referred to the service annually, however up to 25% of women fail to attend their appointment. Little is known about patients' preferences for colposcopic investigation and treatment. This study aims to investigate women's experience of colposcopy, to identify patients' preferences for aspects of appointments within the colposcopy service, and to make suggestions for service improvement. METHODS/DESIGN: This study has been designed as a two stage, mixed method project. Stage one will involve in-depth interviews with new colposcopy patients to ascertain their experience …

Amp-Activated Protein Kinase Regulates Co2-Induced Alveolar Epithelial Dysfunction In Rats And Human Cells By Promoting Na,K-Atpase Endocytosis, István Vadász, Laura A. Dada, Arturo Briva, Humberto E. Trejo, Lynn C. Welch, Jiwang Chen, Peter T. Toth, Emilia Lecuona, Lee A. Witters, Paul T. Schumacker, Navdeep S. Chandel, Werner Seeger, Jacob I. Sznajder

Dartmouth Scholarship

Hypercapnia (elevated CO₂ levels) occurs as a consequence of poor alveolar ventilation and impairs alveolar fluid reabsorption (AFR) by promoting Na,K-ATPase endocytosis. We studied the mechanisms regulating CO₂-induced Na,K-ATPase endocytosis in alveolar epithelial cells (AECs) and alveolar epithelial dysfunction in rats. Elevated CO₂ levels caused a rapid activation of AMP-activated protein kinase (AMPK) in AECs, a key regulator of metabolic homeostasis. Activation of AMPK was mediated by a CO₂-triggered increase in intracellular Ca²⁺ concentration and Ca²⁺/calmodulin-dependent kinase kinase-β (CaMKK-β). Chelating intracellular Ca²⁺ or abrogating CaMKK-β function by gene silencing or …

Gene Expression Profile Of Neuronal Progenitor Cells Derived From Hescs: Activation Of Chromosome 11p15.5 And Comparison To Human Dopaminergic Neurons., William J Freed, Jia Chen, Cristina M Bäckman, Catherine M Schwartz, Tandis Vazin, Jingli Cai, Charles E Spivak, Carl R Lupica, Mahendra S Rao, Xianmin Zeng

Farber Institute for Neuroscience Faculty Papers

BACKGROUND: We initiated differentiation of human embryonic stem cells (hESCs) into dopamine neurons, obtained a purified population of neuronal precursor cells by cell sorting, and determined patterns of gene transcription.

METHODOLOGY: Dopaminergic differentiation of hESCs was initiated by culturing hESCs with a feeder layer of PA6 cells. Differentiating cells were then sorted to obtain a pure population of PSA-NCAM-expressing neuronal precursors, which were then analyzed for gene expression using Massive Parallel Signature Sequencing (MPSS). Individual genes as well as regions of the genome which were activated were determined.

PRINCIPAL FINDINGS: A number of genes known to be involved in the …

Interdependent Group Contingency Management For Cocaine-Dependent Methadone Maintenance Patients., Kimberly C Kirby, Mary Louise Kerwin, Carolyn M Carpenedo, Beth J Rosenwasser, Robert S Gardner

College of Science & Mathematics Departmental Research

Contingency management (CM) for drug abstinence has been applied to individuals independently even when delivered in groups. We developed a group CM intervention in which the behavior of a single, randomly selected, anonymous individual determined reinforcement delivery for the entire group. We also compared contingencies placed only on cocaine abstinence (CA) versus one of four behaviors (CA, treatment attendance, group CM attendance, and methadone compliance) selected randomly at each drawing. Two groups were formed with 22 cocaine-dependent community-based methadone patients and exposed to both CA and multiple behavior (MB) conditions in a reversal design counterbalanced across groups for exposure order. …