Digital Commons Network^™

Parenting Adolescents, Sandra L. D'Angelo, Hatim A. Omar

Pediatrics Faculty Publications

The period of adolescence is often thought to be one of intense stress and turmoil. Yet many parents and teens negotiate this developmental stage without extreme family conflict and without sacrificing close relationships. This review summarizes a portion of the literature on parent-adolescent relationships, focusing on monitoring and control of adolescent behavior and parenting style. Basic principles to emphasize when working with adolescents and parents are also included.

Signaling And Regulation Of G Protein-Coupled Receptors In Airway Smooth Muscle., Charlotte K Billington, Raymond B Penn

Department of Medicine Faculty Papers

Signaling through G protein-coupled receptors (GPCRs) mediates numerous airway smooth muscle (ASM) functions including contraction, growth, and "synthetic" functions that orchestrate airway inflammation and promote remodeling of airway architecture. In this review we provide a comprehensive overview of the GPCRs that have been identified in ASM cells, and discuss the extent to which signaling via these GPCRs has been characterized and linked to distinct ASM functions. In addition, we examine the role of GPCR signaling and its regulation in asthma and asthma treatment, and suggest an integrative model whereby an imbalance of GPCR-derived signals in ASM cells contributes to the …

The Permeability Of The Endoplasmic Reticulum Is Dynamically Coupled To Protein Synthesis, Anirban Roy, William F. Wonderlin

Faculty & Staff Scholarship

No abstract provided.

Plasma Pge-2 Levels And Altered Cytokine Profiles In Adherent Peripheral Blood Mononuclear Cells In Non-Small Cell Lung Cancer (Nsclc), Giovanna E. Hidalgo, Li Zhong, Dennis E. Doherty, Edward A. Hirschowitz

Internal Medicine Faculty Publications

INTRODUCTION: PGE-2 is constitutively produced by many non-small cell lung cancers (NSCLC) and its immunosuppressive effects have been linked to altered immune responses in lung cancer. We asked whether elevated levels of plasma PGE-2 correlated with monocyte IL10 production in the NSCLC environment. Looking for correlation in NSCLC patient blood we assayed plasma from NSCLC patients for PGE2 and IL10; we further evaluated production of IL10 by adherent mononuclear cells from a subset of these patients looking for an altered cytokine profile.

RESULTS: Our initial in vitro experiments show that monocyte IL10 induction correlates with tumor cell PGE-2 production, confirming …

Distinct Neural Systems Subserve Person And Object Knowledge, Jason P. Mitchell, Todd F. Heatherton, C. Neil Macrae

Dartmouth Scholarship

Studies using functional neuroimaging and patient populations have demonstrated that distinct brain regions subserve semantic knowledge for different classes of inanimate objects (e.g., tools, musical instruments, and houses). What this work has yet to consider, however, is how conceptual knowledge about people may be organized in the brain. In particular, is there a distinct functional neuroanatomy associated with person knowledge? By using event-related functional magnetic resonance imaging (fMRI), we measured neural activity while participants made semantic judgments about people or objects. A unique pattern of brain activity was associated with person judgments and included brain regions previously implicated in other …

Characterization Of Subcellular Localization And Stability Of A Splice Variant Of G Alpha I2., Philip B Wedegaertner

Department of Microbiology and Immunology Faculty Papers

BACKGROUND: Alternative mRNA splicing of alpha(i2), a heterotrimeric G protein alpha subunit, has been shown to produce an additional protein, termed salpha(i2). In the salpha(i2) splice variant, 35 novel amino acids replace the normal C-terminal 24 amino acids of alpha(i2). Whereas alpha(i2) is found predominantly at cellular plasma membranes, salpha(i2) has been localized to intracellular Golgi membranes, and the unique 35 amino acids of salpha(i2) have been suggested to constitute a specific targeting signal. RESULTS: This paper proposes and examines an alternative hypothesis: disruption of the normal C-terminus of alpha(i2) produces an unstable protein that fails to localize to plasma …

Effectiveness Of Current Therapy Of Bacterial Vaginosis, Petya M Andreeva, Hatim A. Omar

Pediatrics Faculty Publications

The study was conducted in order to evaluate effectiveness of the treatment of bacterial vaginosis (BV) with different therapeutic regimes according to recommendations of the World Health Organization (WHO). During a one-year period (February 2000-February 2001) the Sexually Transmitted Diseases (STD) Center was visited by 482 women aged 14-51. The diagnosis of BV was established by standard methods: Amsel's clinical criteria and Gram stain of vaginal discharge. The first-line treatment was oral Metronidazole 2 g single dose. Second line was Metronidazole 500 mg twice daily orally for 7 days or oral Clindamycin 300 mg twice daily for seven days. BV …

Short-Circuiting Long-Lived Humoral Immunity By The Heightened Engagement Of Cd40, Loren D. Erickson, Brigit G. Durell, Laura A. Vogel, Brian P. Connor, Marilia Cascalho, Teruhito Yasui, Hitoshi Kikutani, Randolph J. Noelle

Dartmouth Scholarship

Agonistic αCD40 Ab’s have been shown to be potent immune adjuvants for both cell- and humoral-mediated immunity. While enhancing short-lived humoral immunity, the administration of a CD40 agonist during thymus-dependent immune responses ablates germinal center formation, prematurely terminates the humoral immune response, blocks the generation of B cell memory, and prevents the generation of long-lived bone marrow plasma cells. Interestingly, some of these effects of heightened CD40 engagement could be mimicked by enhancing the magnitude of antigen-specific T cell help. Taken together, these studies demonstrate that as the magnitude of CD40 signaling intensifies, the fate of antigen-reactive B cells can …

Vanadate-Induced Expression Of Hypoxia-Inducible Factor 1Α And Vascular Endothelial Growth Factor Through Phosphatidylinositol 3-Kinase/Akt Pathway And Reactive Oxygen Species, Ning Gao, Min Ding, Jenny Z. Zheng, Zhuo Zhang, Stephen S. Leonard, Ke Jian Liu, Xianglin Shi, Bing-Hua Jiang

Faculty & Staff Scholarship

No abstract provided.

Assessment Of Validity Of The National Public Health Performance Standards: The Local Public Health Performance Assessment Instrument., Joyce Beaulieu, F. Douglas Scutchfield

Preventive Medicine and Environmental Health Faculty Publications

The National Public Health Performance Standards Program (NPHPSP) has developed performance standards measurement instruments, based on the 10 "Essential Services of Public Health" that are being tested in several states. This article is a report on the face and content validity of the instrument designed for local public health systems. Judgments about the face validity of the standards were obtained in a survey of local public health systems that had used the instrument in a test state. The validity of each standard was addressed along the following dimensions: the importance of the standard as a measure of the Essential Service; …

Comparing Communication Technology On Chinese, English, And Spanish Diabetes Web Sites, Yanko F Michea, Karen Pancheri, Yang Gong, Elmer Bernstam

Faculty, Staff and Student Publications

Technological and cultural factors influence access to health information on the web in multifarious ways. We evaluated structural differences and availability of communication services on the web in three diverse language and cultural groups: Chinese, English, and Spanish. A total of 382 web sites were analyzed: 144 were English language sites (38%), 129 were Chinese language sites (34%), and 108 were Spanish language sites (28%). We did not find technical differences in the number of outgoing links per domain or the total availability of communication services between the three groups. There were differences in the distribution of available services between …

Analysis Of Mitotic Microtubule-Associated Proteins Using Mass Spectrometry Identifies Astrin, A Spindle-Associated Protein, Gary J. Mack, Duane A. Compton

Dartmouth Scholarship

We purified microtubules from a mammalian mitotic extract and obtained an amino acid sequence from each microtubule-associated protein by using mass spectrometry. Most of these proteins are known spindle-associated components with essential functional roles in spindle organization. We generated antibodies against a protein identified in this collection and refer to it as astrin because of its association with astral microtubule arrays assembled in vitro. Astrin is approximately 134 kDa, and except for a large predicted coiled-coil domain in its C-terminal region it lacks any known functional motifs. Astrin associates with spindle microtubules as early as prophase where it concentrates at …

Role Of Protein Kinase C-Delta In The Regulation Of Collagen Gene Expression In Scleroderma Fibroblasts, Sergio A. Jimenez, Svetlana Gaidarova, Biagio Saitta, Nora Sandorfi, David J. Herrich, Joan C. Rosenbloom, Umberto Kucich, William R. Abrams, Joel Rosenbloom

Selected Works of Sergio Jiménez, MD, MACR

Working with cultured dermal fibroblasts derived from control individuals and patients with systemic sclerosis (SSc), we have examined the effects of protein kinase C-delta (PKC-delta) on type I collagen biosynthesis and steady-state levels of COL1A1 and COL3A1 mRNAs. Rottlerin, a specific inhibitor of PKC-delta, exerted a powerful, dose-dependent inhibition of type I and type III collagen gene expression in normal and SSc cells. Optimal rottlerin concentrations caused a 70-90% inhibition of type I collagen production, a >80% reduction in COL1A1 mRNA, and a >70% reduction in COL3A1 mRNA in both cell types. In vitro nuclear transcription assays and transient transfections …

Eliciting The Low-Activity Aldehyde Dehydrogenase Asian Phenotype By An Antisense Mechanism Results In An Aversion To Ethanol., E Garver, Tu Gc, Q N Cao, M Aini, F Zhou, Y Israel

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

A mutation in the gene encoding for the liver mitochondrial aldehyde dehydrogenase (ALDH2-2), present in some Asian populations, lowers or abolishes the activity of this enzyme and results in elevations in blood acetaldehyde upon ethanol consumption, a phenotype that greatly protects against alcohol abuse and alcoholism. We have determined whether the administration of antisense phosphorothioate oligonucleotides (ASOs) can mimic the low-activity ALDH2-2 Asian phenotype. Rat hepatoma cells incubated for 24 h with an antisense oligonucleotide (ASO-9) showed reductions in ALDH2 mRNA levels of 85% and ALDH2 (half-life of 22 h) activity of 55% equivalent to a >90% inhibition in ALDH2 …

Comparison Of The Quantification Of Caffeine In Human Plasma By Gas Chromatography And Elisa, A. B. Carregaro, W. E. Woods, Thomas Tobin, A. Queiroz-Neto

Veterinary Science Faculty Publications

In the present study we evaluated the precision of the ELISA method to quantify caffeine in human plasma and compared the results with those obtained by gas chromatography. A total of 58 samples were analyzed by gas chromatography using a nitrogen-phosphorus detector and routine techniques. For the ELISA test, the samples were diluted to obtain a concentration corresponding to 50% of the absorbance of the standard curve. To determine whether the proximity between the I₅₀ of the standard curve and that of the sample would bring about a more precise result, the samples were divided into three blocks according …

Biological Methods For Cell-Cycle Synchronization Of Mammalian Cells, Penny Davis, Alan Ho, Steven Dowdy

Open Access Publications

Understanding the molecular and biochemical basis of cellular growth and division involves the investigation of regulatory events that most often occur in a cell-cycle phase-dependent fashion. Studies examining cell-cycle regulatory mechanisms and progression invariably require cell-cycle synchronization of cell populations. Thus, many methods have been established to synchronize cells at specific phases of the cell cycle. Several of the common methods involve pharmacological agents, which act at various points throughout the cell cycle. Because of adverse cellular perturbations resulting from many of the synchronizing drugs used, other synchrony methods that involve less perturbation of biological systems, such as serum deprivation, …

Aluminium Toxicokinetics: An Updated Minireview, Robert A. Yokel, Patrick J. Mcnamara

Pharmaceutical Sciences Faculty Publications

This MiniReview updates and expands the MiniReview of aluminium toxicokinetics by Wilhelm et al. published by this journal in 1990. The use of ²⁶Al, analyzed by accelerator mass spectrometry, now enables determination of Al toxicokinetics under physiological conditions. There is concern about aluminium in drinking water. The common sources of aluminium for man are reviewed. Oral Al bioavailability from water appears to be about 0.3%. Food is the primary common source. Al bioavailability from food has not been adequately determined. Industrial and medicinal exposure, and perhaps antiperspirant use, can significantly increase absorbed aluminium. Inhalation bioavailability of airborne soluble Al …

Ups And Downs Of Mucosal Cellular Immunity Against Protozoan Parasites, Lloyd H. Kasper, Dominique Buzoni-Gatel

Dartmouth Scholarship

No abstract provided.

Regulation Of The Processing Of Glucose-6-Phosphate Dehydrogenase Mrna By Nutritional Status, Batoul Amir-Ahmady, Lisa M. Salati

Faculty & Staff Scholarship

No abstract provided.

Accessory Cell Defect In Unresponsiveness Of Neonates And Aged To Polysaccharide Vaccines., Subbarao Bondada, H Wu, D A Robertson, R L Chelvarajan

Microbiology, Immunology, and Molecular Genetics Faculty Publications

T independent antigens elicit antibody responses in the absence of carrier specific T helper cells but require signals from accessory cells (macrophages and dendritic cells) or specific cytokines. They are further subdivided into TI-1 and TI-2 categories based on the ability of TI-1 but not TI-2 antigens to elicit immune responses from neonates. Most bacterial polysaccharides including the pneumococcal polysaccharide vaccines belong to the TI-2 class. It is hypothesized that defects in accessory cell function play a critical role in the failure of neonates to respond to such TI-2 antigens. Immune responses to these TI-2 stimuli are also reduced in …

The Toxicology Of Aluminum In The Brain: A Review, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

Aluminum is environmentally ubiquitous, providing human exposure. Usual human exposure is primarily dietary. The potential for significant Al absorption from the nasal cavity and direct distribution into the brain should be further investigated. Decreased renal function increases human risk of Al-induced accumulation and toxicity. Brain Al entry from blood may involve transferrin-receptor mediated endocytosis and a more rapid process transporting small molecular weight Al species. There appears to be Al efflux from the brain, probably as Al citrate. There is prolonged retention of a fraction of Al that enters the brain, suggesting the potential for accumulation with repeated exposure. Al …

Role Perceptions Of Occupational Therapists Providing Support And Education For Caregivers Of Persons With Dementia., Susan Toth-Cohen

Department of Occupational Therapy Faculty Papers

OBJECTIVE: This pilot study explored occupational therapists' perceptions of their roles as interventionists providing education and support for caregivers of persons with dementia. The intervention was provided in caregivers' homes as part of a larger funded study.

METHOD: Interviews were conducted with four occupational therapists to elicit their reflections on practice and their views on occupational therapy services on the basis of their experiences providing support and education for caregivers in the funded study.

RESULTS: Key themes consisted of the contrasts between the therapists' roles in the study and their customary practices and the professional and personal impact of their …

Ubinuclein, A Novel Nuclear Protein Interacting With Cellular And Viral Transcription Factors., S Aho, M Buisson, T Pajunen, Y W Ryoo, J F Giot, H Gruffat, A Sergeant, Jouni Uitto

Department of Dermatology and Cutaneous Biology Faculty Papers

The major target tissues for Epstein-Barr virus (EBV) infection are B lymphocytes and epithelial cells of the oropharyngeal zone. The product of the EBV BZLF1 early gene, EB1, a member of the basic leucine-zipper family of transcription factors, interacts with both viral and cellular promoters and transcription factors, modulating the reactivation of latent EBV infection. Here, we characterize a novel cellular protein interacting with the basic domains of EB1 and c-Jun, and competing of their binding to the AP1 consensus site. The transcript is present in a wide variety of human adult, fetal, and tumor tissues, and the protein is …

Global Cns Gene Transfer For A Childhood Neurogenetic Enzyme Deficiency: Canavan Disease., Paola Leone, Christopher G Janson, Scott J Mcphee, Matthew J During

Department of Neurosurgery Faculty Papers

The neurogenetic prototypic disease on which we chose to test our gene therapy strategy is Canavan disease (CD). CD is an autosomal recessive leukodystrophy associated with spongiform degeneration of the brain. At present the disease is uniformly fatal in affected probands. CD is characterized by mutations in the aspartoacylase (ASPA) gene, resulting in loss of enzyme activity. In this review, recent evidence is summarized on the etiology and possible treatments for CD. In particular, we discuss two gene delivery systems representing recent advances in both viral and liposome technology: a novel cationic liposome-polymer-DNA (LPD) complex, DCChol/DOPE-protamine, as well as recombinant …

Beta- And Gamma-Catenin Mutations, But Not E-Cadherin Inactivation, Underlie T-Cell Factor/Lymphoid Enhancer Factor Transcriptional Deregulation In Gastric And Pancreatic Cancer., K Caca, F T Kolligs, X Ji, M Hayes, J Qian, Alan M. Yahanda Md, Facs, D L Rimm, J Costa, E R Fearon

PCI Publications and Projects

Adenomatous polyposis coli (APC) mutations are present in >70% of colon cancers. The APC protein binds to beta-catenin (beta-cat), a protein first identified because of its role in E-cadherin (E-cad) cell adhesion. In some colon cancers lacking APC defects, mutations in presumptive glycogen synthase kinase 3beta phosphorylation sites near the beta-cat NH2 terminus appear to render beta-cat resistant to regulation by APC and glycogen synthase kinase 3beta. In cells with APC or beta-cat defects, beta-cat is stabilized and, in turn, binds to and activates T-cell factor (Tcf)/lymphoid enhancer factor (Lef) transcription factors. To further explore the role of APC, beta-cat, …

A Cbfa1-Dependent Genetic Pathway Controls Bone Formation Beyond Embryonic Development, P Ducy, M Starbuck, M Priemel, J Shen, G Pinero, V Geoffroy, M Amling, G Karsenty

Faculty, Staff and Student Publications

The molecular mechanisms controlling bone extracellular matrix (ECM) deposition by differentiated osteoblasts in postnatal life, called hereafter bone formation, are unknown. This contrasts with the growing knowledge about the genetic control of osteoblast differentiation during embryonic development. Cbfa1, a transcriptional activator of osteoblast differentiation during embryonic development, is also expressed in differentiated osteoblasts postnatally. The perinatal lethality occurring in Cbfa1-deficient mice has prevented so far the study of its function after birth. To determine if Cbfa1 plays a role during bone formation we generated transgenic mice overexpressing Cbfa1 DNA-binding domain (DeltaCbfa1) in differentiated osteoblasts only postnatally. DeltaCbfa1 has a higher …

Integrin-Dependent Control Of Translation: Engagement Of Integrin Alphaiibbeta3 Regulates Synthesis Of Proteins In Activated Human Platelets., Ravinder Pabla, Andrew S. Weyrich, Dan A. Dixon, Paul F. Bray, Thomas M. Mcintyre, Stephen M. Prescott, Guy A. Zimmerman

Cardeza Foundation for Hematologic Research

Integrins are widely expressed plasma membrane adhesion molecules that tether cells to matrix proteins and to one another in cell-cell interactions. Integrins also transmit outside-in signals that regulate functional responses of cells, and are known to influence gene expression by regulating transcription. In previous studies we found that platelets, which are naturally occurring anucleate cytoplasts, translate preformed mRNA transcripts when they are activated by outside-in signals. Using strategies that interrupt engagement of integrin alphaIIbbeta3 by fibrinogen and platelets deficient in this integrin, we found that alphaIIbbeta3 regulates the synthesis of B cell lymphoma 3 (Bcl-3) when platelet aggregation is induced …

Camp-Induced Phosphorylation And Inhibition Of Na + /H + Exchanger 3 (Nhe3) Are Dependent On The Presence But Not The Phosphorylation Of Nhe Regulatory Factor, Mirza Zizak, Georg Lamprecht, Deborah Steplock, Nadeem Tariq, Shirish Shenolikar, Mark Donowitz, C. H. Chris Yun, Edward J. Weinman

Faculty & Staff Scholarship

No abstract provided.

Inhibition Of Fibronectin Matrix Assembly By The Heparin-Binding Domain Of Vitronectin, Denise C. Hocking, Jane Sottile, Thomas Reho, Reinhard Fässler, Paula J. Mckeown-Longo

Biology

The deposition of fibronectin into the extracellular matrix is an integrin-dependent, multistep process that is tightly regulated in order to ensure controlled matrix deposition. Reduced fibronectin deposition has been associated with altered embryonic development, tumor cell invasion, and abnormal wound repair. In one of the initial steps of fibronectin matrix assembly, the amino-terminal region of fibronectin binds to cell surface receptors, termed matrix assembly sites. The present study was undertaken to investigate the role of extracellular signals in the regulation of fibronectin deposition. Our data indicate that the interaction of cells with the extracellular glycoprotein, vitronectin, specifically inhibits matrix assembly …

The Leukemic Protein Core Binding Factor Beta (Cbfbeta)-Smooth-Muscle Myosin Heavy Chain Sequesters Cbfalpha2 Into Cytoskeletal Filaments And Aggregates, Neeraj Adya, Terryl Stacy, Nancy A. Speck, Pu Paul Liu

Dartmouth Scholarship

The fusion gene CBFB-MYH11 is generated by the chromosome 16 inversion associated with acute myeloid leukemias. This gene encodes a chimeric protein involving the core binding factor β (CBFβ) and the smooth-muscle myosin heavy chain (SMMHC). Mouse model studies suggest that this chimeric protein CBFβ-SMMHC dominantly suppresses the function of CBF, a heterodimeric transcription factor composed of DNA binding subunits (CBFα1 to 3) and a non-DNA binding subunit (CBFβ). This dominant suppression results in the blockage of hematopoiesis in mice and presumably contributes to leukemogenesis. We used transient-transfection assays, in combination with immunofluorescence and green fluorescent protein-tagged proteins, to monitor …