Digital Commons Network^™

Crystal Structure Of The Cystic Fibrosis Transmembrane Conductance Regulator Inhibitory Factor Cif Reveals Novel Active-Site Features Of An Epoxide Hydrolase Virulence Factor, Christopher D. Bahl, Christophe Morisseau, Jennifer M. Bomberger, Bruce A. Stanton, Bruce D. Hammock, George A. O'Toole, Dean R. Madden

Dartmouth Scholarship

Cystic fibrosis transmembrane conductance regulator (CFTR) inhibitory factor (Cif) is a virulence factor secreted by Pseudomonas aeruginosa that reduces the quantity of CFTR in the apical membrane of human airway epithelial cells. Initial sequence analysis suggested that Cif is an epoxide hydrolase (EH), but its sequence violates two strictly conserved EH motifs and also is compatible with other alpha/beta hydrolase family members with diverse substrate specificities. To investigate the mechanistic basis of Cif activity, we have determined its structure at 1.8-A resolution by X-ray crystallography. The catalytic triad consists of residues Asp129, His297, and Glu153, which are conserved across the …

Progressive Changes In Microglia And Macrophages In Spinal Cord And Peripheral Nerve In The Transgenic Rat Model Of Amyotrophic Lateral Sclerosis, David J. Graber, William F. Hickey, Brent T. Harris

Dartmouth Scholarship

The role of neuroinflammation in motor neuron death of amyotrophic lateral sclerosis (ALS) is unclear. The human mutant superoxide dismutase-1 (hmSOD1)-expressing murine transgenic model of ALS has provided some insight into changes in microglia activity during disease progression. The purpose of this study was to gain further knowledge by characterizing the immunological changes during disease progression in the spinal cord and peripheral nerve using the more recently developed hmSOD1 rat transgenic model of ALS. Using immunohistochemistry, the extent and intensity of tissue CD11b expression in spinal cord, lumbar nerve roots, and sciatic nerve were evaluated in hmSOD1 rats that were …

Appendicitis: When Simple Becomes Not So Simple, Elizabeth H. Ey, Jeffrey C. Pence

Department of Surgery Faculty Publications

No abstract provided.

A Woman With Hiv Infection, Brain Abscesses, And Eosinophilia, Marcela Campo, Man K Phung, Rehan Ahmed, Paul Cantey, Henry Bishop, Tanvir K Bell, Carolyn Gardiner, Cesar A Arias

Faculty, Staff and Student Publications

No abstract provided.

Aging-In-Place Research At Orcatech: Making Sense Of The Data, Tamara Hayes

Systems Science Friday Noon Seminar Series

The Oregon Center for Aging and Technology (ORCATECH) seeks to facilitate successful aging and reduce the cost of healthcare by establishing the evidence base for technologies supporting aging-in-place research and care. This is done through pilot studies evaluating the role of the technologies, as well as large longitudinal studies in which sensors are placed in the homes of community-dwelling elders to monitor daily patterns of activity, walking speeds, medication adherence, and other behaviors. These sensors collect continuous data that reflect normal variability in behaviors as well as trends that may indicate problematic changes in cognition or mobility. Because data are …

Clinical Profile And Treatment Of Infantile Spasms Using Vigabatrin And Acth - A Developing Country Perspective, S. H. Ibrahim, Shamshad Gulab, Sidra Ishaque, Taimur Saleem

Department of Paediatrics and Child Health

Background: Infantile spasms represent a serious epileptic syndrome that occurs in the early infantile age. ACTH and Vigabatrin are actively investigated drugs in its treatment. This study describes the comparison of their efficacy in a large series of Patients with infantile spasms from Pakistan. Methods: All Patients with infantile spasms who presented to Aga Khan University Hospital, Karachi, Pakistan from January, 2006 to April, 2008 were included in this study. Inclusion criteria were clinical symptoms of infantile spasms, hypsarrythmia or modified hyparrythmia on electroencephalography, at least six months of follow-up period and receipt of any of the two drugs mentioned …

Analysis Of The Uk Recommendations On Obesity Based On A Proposed Implementation Framework, Amudha S. Poobalan, Lorna S. Aucott, Sheraz Ahmed, W. Cairns S. Smith

Department of Paediatrics and Child Health

Background: There is considerable expertise in the obesity field in identifying, appraising, and synthesising evidence to develop guidelines and recommendations for policy and practice. The recommendations, while based on evidence, are not formulated in a way that readily leads to implementation. This paper analyses the recent UK recommendations on obesity using a proposed implementation framework. Methods: Two bibliographic databases (Medline and Embase) and various health related and government websites were systematically searched for obesity recommendations published between 1996 and 2007. All the documents published on recommendations for either prevention or treatment of obesity in the UK were assessed. A proposed …

Anion-Sensitive Regions Of L-Type Cav1.2 Calcium Channels Expressed In Hek293 Cells., Norbert Babai, Nataly Kanevsky, Nathan Dascal, George J. Rozanski, Dhirendra P. Singh, Nigar Fatma, Wallace B. Thoreson

Journal Articles: Ophthalmology

L-type calcium currents (I(Ca)) are influenced by changes in extracellular chloride, but sites of anion effects have not been identified. Our experiments showed that CaV1.2 currents expressed in HEK293 cells are strongly inhibited by replacing extracellular chloride with gluconate or perchlorate. Variance-mean analysis of I(Ca) and cell-attached patch single channel recordings indicate that gluconate-induced inhibition is due to intracellular anion effects on Ca(2+) channel open probability, not conductance. Inhibition of CaV1.2 currents produced by replacing chloride with gluconate was reduced from approximately 75%-80% to approximately 50% by omitting beta subunits but unaffected by omitting alpha(2)delta subunits. Similarly, gluconate inhibition was …

A Comprehensive Approach To Obesity, Hypertension, And Mental Health Evaluation, Stefan G. Kiessling, Kimberly K. Mcclanahan, Hatim A. Omar

Pediatrics Faculty Publications

The global epidemic of childhood and adolescent obesity in developing and developed countries has become a major public health concern. Given the relationship between obesity and hypertension as documented in several landmark studies, it is no surprise that, as the prevalence of obesity has increased in the pediatric population, rates of hypertension have also increased substantially. Hypertension is one of the most important risk factors for cardiovascular diseases and stroke; therefore, evaluation and initiation of appropriate treatment are extremely important in the pediatric population. Evaluation for secondary causes of hypertension, including renovascular, renoparenchymal, and endocrine disease, is the approach most …

Substance Abuse Among Adolescents, Abdel Salous, Hatim A. Omar

Pediatrics Faculty Publications

This chapter aims to provide a global perspective on substance abuse among adolescents across different cultures, and to review appropriate strategies in communicating with the adolescent population about substance abuse. Drug abuse continues to be a major public health issue in the United States, especially among adolescents. The attitude toward and involvement in drug abuse among adolescents is a complex problem shaped by multiple psychosocial parameters. Psychosocial variables such as ethnicity, and religion, and group dynamics, while deeply intertwined in shaping the cultural identity of adolescents, also deliver their impact to substance abuse in this patient population. In a society …

Eosinophilic Cholangitis And Cholangiopathy: A Sheep In Wolves Clothing, Catherine Nashed, Sujit Vijay Sakpal, Victoria Shusharina, Ronald Scott Chamberlain

Department of Surgery

BACKGROUND: Eosinophilic cholangitis (EC) is a rare benign disorder of the biliary tract which can cause biliary obstruction. Similar to other disease processes involving the bile ducts, this disorder can pose a difficult diagnostic challenge as it can mimic cholangiocarcinoma.

METHODS: A systematic search of the scientific literature was carried out using PubMed to access all publications related to EC. Search keywords that were utilized included "eosinophilic cholangitis," "etiology," "treatment," and "obstructive jaundice." Results. Twenty-three cases of EC have been reported. Nineteen patients (82.6%) who presented with EC remain disease-free; 15 of these 19 patients (78.9%) with followup time remain …

Neural Activity In The Hippocampus And Perirhinal Cortex During Encoding Is Associated With The Durability Of Episodic Memory, V. A. Carr, Indre Viskontas, S. A. Engel, B. J. Knowlton

Psychology

Studies examining medial temporal lobe (MTL) involvement in memory formation typically assess memory performance after a single, short delay. Thus, the relationship between MTL encoding activity and memory durability over time remains poorly characterized. To explore this relationship, we scanned participants using high-resolution functional imaging of the MTL as they encoded object pairs; using the remember/know paradigm, we then assessed memory performance for studied items both 10 min and 1 week later. Encoding trials were classified as either subsequently recollected across both delays, transiently recollected (i.e., recollected at 10 min but not after 1 week), consistently familiar, or consistently forgotten. …

Com Outlook Winter 2010, College Of Osteopathic Medicine

COM Outlook

No abstract provided.

Medical Education Digest, Vol. 12 No. 1 (January/February 2010), Nova Southeastern University

Medical Education Digest

No abstract provided.

Spermine Oxidase (Smo) Activity In Breast Tumor Tissues And Biochemical Analysis Of The Anticancer Spermine Analogues Benspm And Cpenspm, Manuela Cervelli, Gabriella Bellavia, Emiliano Fratini, Roberto Amendola, Fabio Polticelli, Marco Barba, Rodolfo Federico, Fabrizio Signore, Giacomo Gucciardo, Rosalba Grillo, Patrick M. Woster, Robert A. Casero Jr, Paolo Mariottini

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Polyamine metabolism has a critical role in cell death and proliferation representing a potential target for intervention in breast cancer (BC). This study investigates the expression of spermine oxidase (SMO) and its prognostic significance in BC. Biochemical analysis of Spm analogues BENSpm and CPENSpm, utilized in anticancer therapy, was also carried out to test their property in silico and in vitro on the recombinant SMO enzyme.

Methods

BC tissue samples were analyzed for SMO transcript level and SMO activity. Student's t test was applied to evaluate the significance of the differences in value observed in T and NT …

Antioxidant Rich Grape Pomace Extract Suppresses Postprandial Hyperglycemia In Diabetic Mice By Specifically Inhibiting Alpha-Glucosidase, Shelly Hogan, Lei Zhang, Jianrong Li, Shi Sun, Corene Canning, Kequan Zhou

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Postprandial hyperglycemia is an early defect of type 2 diabetes and one of primary anti-diabetic targets. Treatment of postprandial hyperglycemia can be achieved by inhibiting intestinal α-glucosidase, the key enzyme for oligosaccharide digestion and further glucose absorption. Grape pomace is winemaking byproduct rich in bioactive food compounds such as phenolic antioxidants. This study evaluated the anti-diabetic potential of two specific grape pomace extracts by determining their antioxidant and anti-postprandial hyperglycemic activities in vitro and in vivo.

Methods

The extracts of red wine grape pomace (Cabernet Franc) and white wine grape pomace (Chardonnay) were prepared in 80% ethanol. An …

Angiogenesis Inhibitors In The Treatment Of Prostate Cancer, Clara Hwang, Elisabeth I. Heath

Wayne State University Associated BioMed Central Scholarship

Abstract

Prostate cancer remains a significant public health problem, with limited therapeutic options in the setting of castrate-resistant metastatic disease. Angiogenesis inhibition is a relatively novel antineoplastic approach, which targets the reliance of tumor growth on the formation of new blood vessels. This strategy has been used successfully in other solid tumor types, with the FDA approval of anti-angiogenic agents in breast, lung, colon, brain, and kidney cancer. The application of anti-angiogenic therapy to prostate cancer is reviewed in this article, with attention to efficacy and toxicity results from several classes of anti-angiogenic agents. Ultimately, the fate of anti-angiogenic agents …

Vaccination With A Plasmid Dna Encoding Her-2/Neu Together With Low Doses Of Gm-Csf And Il-2 In Patients With Metastatic Breast Carcinoma: A Pilot Clinical Trial, Hã¥Kan Norell, Isabel Poschke, Jehad Charo, Wei Z. Wei, Courtney Erskine, Marie P. Piechocki, Keith L. Knutson, Jonas Bergh, Elisabet Lidbrink, Rolf Kiessling

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Adjuvant trastuzumab (Herceptin) treatment of breast cancer patients significantly improves their clinical outcome. Vaccination is an attractive alternative approach to provide HER-2/neu (Her2)-specific antibodies and may in addition concomitantly stimulate Her2-reactive T-cells. Here we report the first administration of a Her2-plasmid DNA (pDNA) vaccine in humans.

Patients and Methods

The vaccine, encoding a full-length signaling-deficient version of the oncogene Her2, was administered together with low doses of GM-CSF and IL-2 to patients with metastatic Her2-expressing breast carcinoma who were also treated with trastuzumab. Six of eight enrolled patients completed all three vaccine cycles. In the remaining two patients …

Sulforaphane Induces Cell Cycle Arrest By Protecting Rb-E2f-1 Complex In Epithelial Ovarian Cancer Cells, Christopher S. Bryant, Sanjeev Kumar, Sreedhar Chamala, Jay Shah, Jagannath Pal, Mahdi Haider, Shelly Seward, Aamer M. Qazi, Robert Morris, Assaad Semaan, Masood A. Shammas, Christopher Steffes, Ravindra B. Potti, Madhu Prasad, Donald W. Weaver, Ramesh B. Batchu

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Sulforaphane (SFN), an isothiocyanate phytochemical present predominantly in cruciferous vegetables such as brussels sprout and broccoli, is considered a promising chemo-preventive agent against cancer. In-vitro exposure to SFN appears to result in the induction of apoptosis and cell-cycle arrest in a variety of tumor types. However, the molecular mechanisms leading to the inhibition of cell cycle progression by SFN are poorly understood in epithelial ovarian cancer cells (EOC). The aim of this study is to understand the signaling mechanisms through which SFN influences the cell growth and proliferation in EOC.

Results

SFN at concentrations of 5 - 20 …

Elevated Csf Outflow Resistance Associated With Impaired Lymphatic Csf Absorption In A Rat Model Of Kaolin-Induced Communicating Hydrocephalus, Gurjit Nagra, Mark E. Wagshul, Shams Rashid, Jie Li, J Pat Mcallister Ii, Miles Johnston

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

We recently reported a lymphatic cerebrospinal fluid (CSF) absorption deficit in a kaolin model of communicating hydrocephalus in rats with ventricular expansion correlating negatively with the magnitude of the impediment to lymphatic function. However, it is possible that CSF drainage was not significantly altered if absorption at other sites compensated for the lymphatic defect. The purpose of this study was to investigate the impact of the lymphatic absorption deficit on global CSF absorption (CSF outflow resistance).

Methods

Kaolin was injected into the basal cisterns of Sprague Dawley rats. The development of hydrocephalus was assessed using magnetic resonance imaging …

Pulmonary Carcinosarcoma Initially Presenting As Invasive Aspergillosis: A Case Report Of Previously Unreported Combination, Ariyo O. Olobatoke, Doina David, Wasif Hafeez, Thien Van, Husain A. Saleh

Wayne State University Associated BioMed Central Scholarship

Abstract

Carcinosarcoma of the lung is a malignant tumor composed of a mixture of carcinoma and sarcoma elements. The carcinomatous component is most commonly squamous followed by adenocarcinoma. The sarcomatous component commonly comprises the bulk of the tumor and shows poorly differentiated spindle cell features. Foci of differentiated sarcomatous elements such as chondrosarcoma and osteosarcoma may be seen. Aspergillus pneumonia is the most common form of invasive aspergillosis and occurs mainly in patients with malignancy, immunocompromizing or debilitating diseases. Patients with Aspergillus pneumonia present with fever, cough, chest pain and occasionally hemoptysis. Tissue examination is the most reliable method for …

Nuclear Factor-Kappa B Localization And Function Within Intrauterine Tissues From Term And Preterm Labor And Cultured Fetal Membranes, Sonali Vora, Asad Abbas, Chong J. Kim, Taryn Ls Summerfield, Juan P. Kusanovic, Jay D. Iams, Roberto Romero, Douglas A. Kniss, William E. Ackerman Iv

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

The objective of this study was to quantify the nuclear localization and DNA binding activity of p65, the major transactivating nuclear factor-kappa B (NF-kappaB) subunit, in full-thickness fetal membranes (FM) and myometrium in the absence or presence of term or preterm labor.

Methods

Paired full-thickness FM and myometrial samples were collected from women in the following cohorts: preterm no labor (PNL, N = 22), spontaneous preterm labor (PTL, N = 21), term no labor (TNL, N = 23), and spontaneous term labor (STL, N = 21). NF-kappaB p65 localization was assessed by immunohistochemistry, and DNA binding activity was …

Nuclear Expression Of Klf6 Tumor Suppressor Factor Is Highly Associated With Overexpression Of Erbb2 Oncoprotein In Ductal Breast Carcinomas, Ricardo C. Gehrau, Diego S. D'Astolfo, Catherine I. Dumur, Jose L. Bocco, Nicolas P. Koritschoner

Pathology Publications

Background

Krüppel-like factor 6 (KLF6) is an evolutionarily conserved and ubiquitously expressed protein that belongs to the mammalian Sp1/KLF family of transcriptional regulators. Though KLF6 is a transcription factor and harbors a nuclear localization signal it is not systematically located in the nucleus but it was detected in the cytoplasm of several tissues and cell lines. Hence, it is still not fully settled whether the tumor suppressor function of KLF6 is directly associated with its ability to regulate target genes.

Methodology/Principal Findings

In this study we analyzed KLF6 expression and sub-cellular distribution by immunohistochemistry in several normal and tumor tissues …

On Becoming Invisible, Edward F. Ansello

Director's Editorials from Age in Action

Age or impairment tends to render us less likely to be noticed. We can readjust how we see those becoming invisible.

Filling The Gap, Edward F. Ansello

Director's Editorials from Age in Action

There is need for multiple initiatives focusing on the pipeline from professional undergraduate education through the continuing education of current practitioners, in order to make some dent in the looming shortfall of geriatric health care providers. It is particularly gratifying to announce that Virginia has been awarded federal funding of a Geriatric Education Center (VGEC). The overall goal of the VGEC is to improve the training of health professionals in geriatrics.

The Blank Tablet Of Aging, Edward F. Ansello

Director's Editorials from Age in Action

The 16th annual conference of the Virginia Coalition for the Prevention of Elder Abuse (VCPEA) will include the basics of geriatric crisis assessment, depression and suicide among older adults; alcohol and medication misuse; older prisoners; training faith and community-based leaders to respond to domestic violence in later life; and brain injury in later life as a precipitant or a consequence of mistreatment. The Area Planning and Services Committee (APSC) conference will recognize the values, opportunities, and challenges associated with growing older with lifelong disabilities. These two conferences symbolize how we as a people can celebrate the good and confront the …

Aging As An Option, Edward F. Ansello

Director's Editorials from Age in Action

Sometimes people treat aging as if it were an option or a discretionary exercise. Aging is neither a fad nor an option but a bedrock reality that should be constantly under consideration, especially by those charged with protecting the common good. We need to remember that we should not treat aging and aging-related research, training, and services as an option.

Aging And The Behavioral Problems Of Brain Injury, Paul F. Aravich, Marylin Copeland

Case Studies from Age in Action

Educational Objectives

1. List the various classes of brain injury.

2. Identify cognitive and emotional problems as among the most common and disabling complications of brain injury.

3. Assess challenges to successful aging with a brain injury.

4. Examine the consequences of inadequate systems of care for the challenging behaviors produced by brain injury.

Senior Meal Programs: Feeding A Crowd With Local Foods, Gordon Walker, Elyse Thierry

Case Studies from Age in Action

Educational Objectives

1. Examine reasons for an institutional meal program to consider incorporating local food.

2. Identify potential community partners who might assist in moving such a program forward and the mutual benefits.

3. Describe the possible changes that an institution’s local food program can foster in the community at large.

Cpr And Dnr Decision Making, Viki Kind

Case Studies from Age in Action

Educational Objectives

1. Examine the complexities of end-of-life care and obstacles to good DNR decision making.

2. Discuss CPR and its perceived vs. actual chances for success.

3. Demonstrate best practices for communicating about CPR.

4. Consider how the signing of the DNR is just one component of endof- life care.