Digital Commons Network^™

Unfolded Protein Response In Cancer: The Physician's Perspective, Xuemei Li, Kezhong Zhang, Zihai Li

Wayne State University Associated BioMed Central Scholarship

Abstract

The unfolded protein response (UPR) is a cascade of intracellular stress signaling events in response to an accumulation of unfolded or misfolded proteins in the lumen of the endoplasmic reticulum (ER). Cancer cells are often exposed to hypoxia, nutrient starvation, oxidative stress and other metabolic dysregulation that cause ER stress and activation of the UPR. Depending on the duration and degree of ER stress, the UPR can provide either survival signals by activating adaptive and antiapoptotic pathways, or death signals by inducing cell death programs. Sustained induction or repression of UPR pharmacologically may thus have beneficial and therapeutic …

Regulation Of Membrane-Type 1 Matrix Metalloproteinase Abundance By Selective Modulation Of Microrna-133a, Adam William Akerman

MUSC Theses and Dissertations

Background: A significant increase in the myocardial abundance of Membrane-Type 1 Matrix Metalioproteinase (MT1-MMP) has been identified in patients suffering Dilated Cardiomyopathy (DCM). These increased levels likely contribute to DCM; however, the molecular basis for up-regulation of MT1-MMP in the context of DCM remains unknown. Of significant relevance, microRNAs fine-tune protein translation by interrupting ribonucleoprotein:mRNA complexes, inducing degradation, or more commonly, translational repression of the message. Therefore, the aim of this study was to identify an endogenous microRNA responsible for the specific alterations correlating with disease state, and demonstrate a method of translational regulation of MT1-MMP. Methods and results: To …

Laparoscopic Drainage Of A Hepatic Echinococcal Cyst: A Case Report, Steven B. Goldin, James J. L. Mateka, Michael J. Schnaus, Sujat Dahal

Surgery Faculty Publications

The Echinococcus granulosus tapeworm causes hepatic echinococcosis. It is endemic in the Mediterranean region, Middle East, and South America. Human infection is secondary to accidental consumption of ova in feces. Absorption through the bowel wall and entrance into the portal circulation leads to liver infection. This case involves a 34 y/o Moroccan male with an echinococcal liver cyst. His chief complaint was RUQ pain. The patient was treated with albendazole and praziquantel. His PMH and PSH was noncontributory. Patient was not on any other medications. ROS was otherwise unremarkable. The patient was AF VSS. He was tender to palpation in …

Digest Of The Philadelphia College Of Osteopathic Medicine (Winter 2011), Philadelphia College Of Osteopathic Medicine

Digest

The Winter 2011 issue of the Digest of the Philadelphia College of Osteopathic Medicine includes the following articles:

• Opening Remarks
• PCOM Updates
• Development News
• Strategic Initiative
• Founders’ Day 2011
• A Cry for Help
• Class Notes
• In Memoriam
• My Turn Essay

Fatty Acyl Amide Dderivatives Of Doxorubicin: Synthesis And In Vitro Anticancer Activities, Bhupender S. Chhikara, Nicole St. Jean, Deendayal Mandal, Anil Kumar, Keykavous Parang

Pharmacy Faculty Articles and Research

Doxorubicin is an anticancer drug extensively used in anticancer therapy. Doxorubicin is highly hydrophilic, has short half-life, and its use is associated with severe side effects at high doses. Fatty acyl amide derivatives of doxorubicin were synthesized with the expectation to improve the lipophilicity and anticancer activity of the drug. The lipophilicity was enhanced with the increase in chain length of fatty acyl moiety. Conjugation of 4-amino group with fatty acids through an amide bond reduced the anticancer activity in leukemia, breast, ovarian, and colon cancer cell lines, suggesting that the presence of free amino group is required for anticancer …

Should Benzodiazepines Be Prescribed To Treat Insomnia And Anxiety Related Disorders?, Judith Nicole Margareten

The Science Journal of the Lander College of Arts and Sciences

The following is an excerpt of the introduction of this article: Benzodiazepines are commonly prescribed drugs used to treat insomnia and anxiety. They are often found in forms such as Xanax (alprazolam) and Valium (diazepam). For many, these drugs have proven essential for ensuring a restful night’s sleep, but for others they are the cause of sleepless ones. Negative effects of benzodiazepines such as addiction, dependence, and impaired cognition plague many patients. While doctors are prone to prescribe these medications readily due to their high level of effectiveness, this practice can pose a great risk to certain populations.

A Proposed Mechanism For Drug-Induced Nightmares, Isaac Brezner

The Science Journal of the Lander College of Arts and Sciences

The following is the introduction of this article: The fields of neuropharmacology and psychopharmacology are known to be highly connected, despite our severe lack of knowledge in these fields. One of the many overlaps between the two fields is sleep, which itself entails many mechanisms and events which are, as of yet, unexplainable. From the perspective of either field, one of the most mysterious events occurring during sleep is dreaming. From the cause of dreams to their content, little is known about them or their more sinister subclassification: nightmares. In this field of disturbed dreaming, neuropharmacology makes a large intrusion …

The Role Of Lipoproteins/Cholesterol In Genomic Instability And Chromosome Mis-Segregation In Alzheimer's And Cardiovascular Disease, Antoneta Granic

USF Tampa Graduate Theses and Dissertations

Several lines of evidence link Alzheimer's disease (AD) to atherosclerosis (CVD), including that elevated low density lipoprotein (LDL)-cholesterol is a common risk factor. Development of genomic instability could also link the two diseases. Previous fluorescence in situ hybridization (FISH) analyses revealed a clonal expansion of aneuploid smooth muscle cells underlying atherosclerotic plaques. Likewise, cellular and mouse models of AD revealed tau-dependent mitotic defects and subsequent aneuploidy partly resulting from amyloid-beta (A&beta) interference with microtubule (MT) stability, and specific MT motors function. Moreover, AD patients develop aneuploid/hyperploid cells in brain and peripheral tissues, implicating similar mechanism that may lead to apoptosis …

Mitochondria, Amyloid Β, And Alzheimer's Disease, Ryan Douglas Readnower, Andrew David Sauerbeck, Patrick G. Sullivan

Spinal Cord and Brain Injury Research Center Faculty Publications

Hypometabolism is a hallmark of Alzheimer's disease (AD) and implicates a mitochondrial role in the neuropathology associated with AD. Mitochondrial amyloid-beta (Aβ) accumulation precedes extracellular Aβ deposition. In addition to increasing oxidative stress, Aβ has been shown to directly inhibit mitochondrial enzymes. Inhibition of mitochondrial enzymes as a result of oxidative damage or Aβ interaction perpetuates oxidative stress and leads to a hypometabolic state. Additionally, Aβ has also been shown to interact with cyclophilin D, a component of the mitochondrial permeability transition pore, which may promote cell death. Therefore, ample evidence exists indicating that …

Biochemical Comparison Of Osteoarthritic Knees With And Without Effusion, Nicole M. Cattano, Jeffrey B. Driban, Easwaran Balasubramanian, Mary F. Barbe, Mamta Amin, Michael R. Sitler

Sports Medicine Faculty Publications

No abstract provided.

A Double-Blind, Randomized, Placebo Controlled Trial Of Ramelteon For The Treatment Of Insomnia And Mood Stability In Patients With Euthymic Bipolar Disorder (Poster), Edward R. Norris Md, Fapa, Fapm, Karen Burke Rn, Julia R. Correll Ba, Ken Zemanek Md, Joel Lerman Md, Michael Kaufmann Md

Department of Psychiatry

No abstract provided.

Adequacy Of Diabetes Care For Older U.S. Rural Adults: A Cross-Sectional Population Based Study Using 2009 Brfss Data, M. Nawal Lutfiyya, Joel E. Mccullough, Lori Mitchell, L. Scott Dean, Martin S. Lipsky

Community Health Faculty Publications and Presentations

Background: In the U.S. diabetes prevalence estimates for adults ≥ 65 years exceed 20%. Rural communities have higher proportions of older individuals and health disparities associated with rural residency place rural communities at risk for a higher burden from diabetes. This study examined the adequacy of care received by older rural adults for their diabetes to determine if older rural adults differed in the receipt of adequate diabetes care when compared to their non-rural counterparts.

Methods: Cross-sectional data from the 2009 Behavioral Risk Factor Surveillance Survey were examined using bivariate and multivariate analytical techniques.

Results: Logistic regression analysis revealed that …

Validation Of Updated Partin’S Table In Pakistani Patients Undergoing Radical Prostatectomy For Prostate Cancer, Nazim Muhammad, Farhat Abbas, Nuzhat Faruqui, Muhammad Islam, Zubair Ahmad

Section of Urology

Objectives: To establish the usefulness and validity of 2007 Partin’s table in our population with prostate cancer.
Materials and methods: Between January 1998 to June 2009, all patients with clinically localized carcinoma prostate who were treated with intent of radical retro-pubic prostatectomy (RRP) were included. Clinical, operative and pathological data was gathered. All biopsy and final histopathology Gleason scores were re-assigned in a double blind manner. Pre-operative serum PSA, TNM clinical stage and biopsy Gleason scores were plotted on Partin’s table and its predictive value and pathological findings of specimen were compared and analyzed by using Receiver operating characteristic …

Attention-Deficit/Hyperactivity Disorder In Childhood Is Associated With Cognitive Test Profiles In The Geriatric Population But Not With Mild Cognitive Impairment Or Alzheimer's Disease, N. Ivanchak, Erin L. Abner, S. A. Carr, S. J. Freeman, A. Seybert, John Ranseen, Gregory A. Jicha

Sanders-Brown Center on Aging Faculty Publications

The frequency of ADHD in the aging population and its relationship to late-life cognitive decline has not been studied previously. To address this gap in our understanding, the Wender-Utah ADHD Rating scale (WURS) was administered to 310 geriatric subjects with cognitive status ranging from normal cognition to mild cognitive impairment to overt dementia. The frequency of WURS-positive ADHD in this sample was 4.4%. WURS scores were not related to cognitive diagnoses, but did show nonlinear associations with tasks requiring sustained attention. The frequency of ADHD appears stable across generations and does not appear to be associated with MCI or dementia …

Course And Outcome Of Obstetric Patients Admitted To A University Hospital Intensive Care Unit, F. Githae, Vitalis Mung’Ayi, William Stones

Anaesthesiology, East Africa

Background: Obstetric Critical Care is an important service in the reduction of maternal morbidity and mortality, but few developing country data are available.

Objectives: To review all maternity patients admitted to the ICU over a seven year period to determine the causes and outcomes of these admissions and the frequency and causes of maternal morbidity and mortality.

Design: Retrospective patient file and ICU chart review.

Subjects: ICU Charts and medical files of obstetric patients admitted to the ICU at The Aga Khan University Hospital between (November 2003 – November 2010) were reviewed.

Setting: The ICU at The Aga Khan University …

Associatioin Of Plasma Aβ Peptides With Blood Pressure In The Elderly, Jean-Charles Lambert, Jean Dallongeville, Kathryn A. Ellis, Susanna Schraen-Maschke, James Lui, Simon Laws, Julie Dumont, Florence Richard, Dominque Cottel, Claudine Berr, David Ames, Colin L. Masters, Christopher C. Rowe, Cassandra Szoeke, Christophe Tzourio, Jean-Francois Dartigues, Luc Buee, Ralph Martins, Philippe Amouyel

Research outputs 2011

Background Aß peptides are often considered as catabolic by-products of the amyloid ß protein precursor (APP), with unknown physiological functions. However, several biological properties have been tentatively attributed to these peptides, including a role in vasomotion. We assess whether plasma Aß peptide levels might be associated with systolic and diastolic blood pressure values (SBP and DBP, respectively). Methodology/Principal Findings Plasma Aß1-40 and Aß1-42 levels were measured using an xMAP-based assay in 1,972 individuals (none of whom were taking antihypertensive drugs) from 3 independent studies: the French population-based 3C and MONA-LISA (Lille) studies (n = 627 and n = 769, respectively) …

Anthropometric Measurements As A Risk For Hypertensive Disorders In Pregnancy: A Hospital Based Study In South Asian Population, Ferha Saeed, Ahmed Jawad, Asma Azmat, Iqbal Azam Syed, Safdar Kagazwala

Department of Obstetrics & Gynaecology

Objectives: To determine the relationship between pregnancy induced hypertensive diseases and obesity.

Methods: A retrospective case controlled study was performed at Aga Khan University Hospital including records from July 2000 to June 2005. All women developing hypertension with or without proteinuria after 20 weeks of pregnancy (n = 218) were included. Categories of pregnancy induced hypertensive diseases (PIHD) were defined according to National high blood pressure working group and ACOG committee bulletin. Controls were selected randomly with a ratio of 1:1.7 between cases and controls.

Results: The estimated prevalence of pre-eclampsia in our institution is 1.9%. Earlier reports suggested mostly …

Serum Monocyte Chemoattractant Protein-1 In Pancreatic Cancer., Jennifer Sullivan, Qiaoke Gong, Terry Hyslop, Harish Lavu, Galina Chipitsyna, Charles Yeo, Hwyda A Arafat

Department of Surgery Faculty Papers

Background/Aims. Pancreatic ductal adenocarcinoma (PDA) has etiological association with chronic inflammation. Elevated circulating levels of inflammatory mediators, such as monocyte chemoattractant protein-1 (MCP-1), are found in obese individuals. We hypothesized that serum MCP-1 levels are elevated in obese PDA patients. Methods. ELISA was used to analyze MCP-1 serum levels in PDA (n = 62) and intraductal papillary mucinous neoplasms (IPMN) (n = 27). Recursive partitioning statistical analysis investigated the relationship between log MCP-1 and clinicopathological parameters. Results. Log MCP-1 values were significantly (P < 0.05) elevated in patients with BMI ≥ 37.5. In patients with BMI < 37.5, average log MCP-1 values were significantly elevated in PDA patients when compared to IPMN patients. Within the IPMN group, higher log MCP-1 levels correlated with increased age. Recursive partitioning analysis of IPMN versus PDA revealed a strategy of predicting characteristics of patients who are more likely to have cancer. This strategy utilizes log MCP-1 as the primary factor and also utilizes smoking status, gender, and age. Conclusion. MCP-1 is a promising biomarker in pancreatic cancer. The potential of using MCP-1 to distinguish PDA from IPMN patients must be studied in larger populations to validate and demonstrate its eventual clinical utility.

Neurologic Improvement After Thoracic, Thoracolumbar, And Lumbar Spinal Cord (Conus Medullaris) Injuries, James S. Harrop, Md, Swetha Naroji, Mitchell G. Maltenfort, Phd, John K. Ratliff, Md, Stavropoula L. Tjoumakaris, Brian Frank, D. Greg Anderson, M.D., Todd Albert, Md, Alexander R. Vaccaro, Md, Phd

Department of Orthopaedic Surgery Faculty Papers

Study Design. Retrospective. Objective. With approximately 10,000 new spinal cord injury (SCI) patients in the United States each year, predicting public health outcomes is an important public health concern. Combining all regions of the spine in SCI trials may be misleading if the lumbar and sacral regions (conus) have a neurologic improvement at different rates than the thoracic or thoracolumbar spinal cord.

Summary of Background Data. Over a 10-year period between January 1995 to 2005, 1746 consecutive spinal injured patients were seen, evaluated, and treated through a level 1 trauma referral center. A retrospective analysis was performed on 150 patients …

Altered Leptin Signaling On Dendritic Cells As A Potential Mechanism For Cancer Immunotherapy, Lorena Y. De Los Santos

Open Access Theses & Dissertations

Leptin is a pleiotropic hormone synthesized primarily by white adipocytes and its receptors are expressed in a variety of tissues and cells such as in the hypothalamus and cells of the immune system. Multiple cell types can produce a considerable amount of leptin such as skeletal muscle, placenta, and osteoblasts to name a few and its synthesis has been shown to be regulated by sex hormones and a broad range of inflammatory mediators. Although leptin has been shown to directly affect immune response, we are interested in how leptin affects dendritic cell function and their ability to induce a proper …

Adrenal Beta-Arrestin 1 Inhibition In Vivo Attenuates Post-Myocardial Infarction Progression To Heart Failure And Adverse Remodeling Via Reduction Of Circulating Aldosterone Levels, Anastasios Lymperopoulos, Phd, Giuseppe Rengo, Md, Carmela Zincarelli, Md, Jihee Kim, Phd, Walter J. Koch, Phd

Center for Translational Medicine Faculty Papers

ABSTRACT

OBJECTIVES: We investigated whether adrenal betaarrestin 1 (betaarr1)-mediated aldosterone production plays any role in post-MI HF progression.

BACKGROUND: Heart failure (HF) represents one of the most significant health problems worldwide and new and innovative treatments are needed. Aldosterone contributes significantly to HF progression after myocardial infarction (MI) by accelerating adverse cardiac remodeling and ventricular dysfunction. It is produced by the adrenal cortex after angiotensin II (AngII) activation of AngII type 1 receptors (AT1Rs), G protein-coupled receptors (GPCRs) that also signal independently of G proteins. G protein-independent signaling is mediated by betaarrestin (betaarr) -1 and -2. We recently reported that …

Is Actemra (Tocilizumab) In Combination With Methotrexate An Effective Treatment For Rheumatoid Arthritis In Patients Who Had An Inadequate Response To Methotrexate Alone?, Jennifer Nagle

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this systematic review is to determine whether or not Actemra (tocilizumab) in combination with methotrexate is an effective treatment for rheumatoid arthritis in patients who had an inadequate response to methotrexate alone. Previous studies have shown other biologic agents and disease modifying antirheumatic drugs (DMARDs) to have some efficacy in treating rheumatoid arthritis. However, tocilizumab is a newly approved FDA drug and therefore, its efficacy in treating RA has yet to be determined.

Is Extract Err731 From The Rheum Rhaponticum Effective In Relieving Menopausal Symptoms In Women Aged 45 To 55 Years Of Age?, Annette M. Merlino

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: To determine whether ERr 731 extract from the Rheum rhaponticum plant is effective in relieving symptoms of menopausal symptoms in women aged 45 to 55 years of age

Does Dietary Intervention Have An Effect On The Progression And Ultimately The Treatment Of Prostate Cancer?, Jenna M. Lombardi

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this systematic review is to determine whether or not dietary intervention has an effect on the progression and ultimately the treatment of Prostate cancer.

Optimal Port Placement And Automated Robotic Positioning For Instrumented Laparoscopic Biosensors, Brady King

Wayne State University Dissertations

OPTIMAL SURGICAL PORT PLACEMENT AND AUTOMATED ROBOTIC POSITIONING FOR RAMAN AND OTHER BIOSENSORS

by

BRADY KING

January 2011

Advisors: Dr. Abhilash Pandya, Dr. Darin Ellis, Dr. Le Yi Wang, and Dr. Greg Auner

Major: Computer Engineering

Degree: Doctor of Philosophy

Medical biosensors can provide new information during minimally invasive and robotic surgical procedures. However, these biosensors have significant physical limitations that make it difficult to find optimal port locations and place them in vivo. This dissertation explores the application of robotics and virtual/augmented reality to biosensors to enable their optimal use in vivo.

In the first study, human …

Human Trophoblast Survival And Invasion In The Developing Placenta: Autocrine Regulation By Hbegf, Philip Jessmon

Wayne State University Dissertations

HBEGF is a multifunctional protein in early pregnancy that induces cytotrophoblast (CTB) cell differentiation to an invasive phenotype, protects against apoptosis, and is involved in an autocrine signaling mechanism that leads to its own protein synthesis. CTBs exist in a low O₂ environment during the first 10 weeks of implantation, during which they invade the decidualized uterine stroma. Inhibitors of intracellular signaling pathways demonstrated that at 20% O₂ HBEGF induces an increase in cell migration through the ERK, MAPK14, JNK, or PIK3 pathways downstream of signaling through its ERBB receptors. Also downstream of these four pathways, HBEGF induces …

Differences In Breast Cancer Tumor Size, Stage, And Survival By Socioeconomic Position In Young Women, Julie Maureen Tomaska

Walden Dissertations and Doctoral Studies

Although the incidence of breast cancer in women under 40 years of age is somewhat rare, young women tend to present with cancer that is more advanced and with poorer prognostic characteristics. This research will be important to providers, women and their families and those seeking to clarify screening guidelines. The purpose of this quantitative, retrospective, cohort study was to evaluate differences in prognostic characteristics by socioeconomic position (SIP). The cohort was comprised of females aged 18 to 39 with a primary diagnosis of breast cancer. Data were obtained from the Surveillance, Epidemiology and End Results registry for all primary …

Development Of A Novel Metallo-Lipid Microparticle Delivery System For A Leishmania Mexicana Dna Vaccine Candidate, Joanna B. Valencia

Open Access Theses & Dissertations

ABSTRACT

Background and Significance.

The leishmaniases are an important group of neglected tropical parasitic diseases caused by parasitic protozoa of the genus Leishmania. International health authorities estimate that 350 million people around the world are at risk for contracting leishmaniasis. Two million new cases occur each year and 12 million people are presently infected worldwide. Leishmaniasis is endemic throughout the Americas region including all of Central America, most of South America, Mexico and southern Texas. Leishmania is also considered a threat to the military readiness of U.S. troops deployed to the Middle East or Latin America.

First- and second-line treatments …

Prenatal Programming Of Human Neurological Function, Curt A. Sandman, Elyssia Poggi Davis, Claudia Buss, Laura M. Glynn

Psychology Faculty Articles and Research

The human placenta expresses the genes for proopiomelanocortin and the major stress hormone, corticotropin-releasing hormone (CRH), profoundly altering the "fight or flight" stress system in mother and fetus. As pregnancy progresses, the levels of these stress hormones, including maternal cortisol, increase dramatically. These endocrine changes are important for fetal maturation, but if the levels are altered (e.g., in response to stress), they influence (program) the fetal nervous system with long-term consequences. The evidence indicates that fetal exposure to elevated levels of stress hormones (i) delays fetal nervous system maturation, (ii) restricts the neuromuscular development and alters the stress response of …

Suggested Improvements For The Allergenicity Assessment Of Genetically Modified Plants Used In Foods, Richard E. Goodman

Department of Food Science and Technology: Faculty Publications

Genetically modified (GM) plants are increasingly used for food production and industrial applications. As the global population has surpassed 7 billion and per capita consumption rises, food production is challenged by loss of arable land, changing weather patterns, and evolving plant pests and disease. Previous gains in quantity and quality relied on natural or artificial breeding, random mutagenesis, increased pesticide and fertilizer use, and improved farming techniques, all without a formal safety evaluation. However, the direct introduction of novel genes raised questions regarding safety that are being addressed by an evaluation process that considers potential increases in the allergenicity, toxicity, …