Digital Commons Network^™

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.

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 …

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 …

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.

Treatment Strategies In Acute Myelogenous Leukemia : Investigating Hsp90 And P53 As Targets, Jennifer M. Napper

Theses, Dissertations and Capstones

Acute myelogenous leukemia (AML) is the deadliest of the lymphatic and bone marrow cancers. Patients diagnosed with AML have a five year survival rate of 23.4%. AML is characterized by an accumulation of undifferentiated and functionless myeloid precursors in the bone marrow and blood. Heat shock protein 90 (Hsp90) inhibitors, such as 17-AAG, an analog of geldanamycin (GM), are currently undergoing phase I, and II and III clinical trials for various cancers with mixed results. I found distinct responses to 17-AAG treatment among the AML cell lines tested. I also discovered two mutant TP53 alleles in Kasumi-3 cells, an AML …

Genetic And Environmental Factors Suggest That Dietary Fatty Acid Content, Lipid Metabolism, And Bone Properties Are Key Regulators Of Myeloid Progenitor Cell Frequency, Melinda E. Varney

Theses, Dissertations and Capstones

Acute myelogenous leukemia (AML) and its precursors are the result of the dysregulation of hematopoiesis. Hematopoiesis proceeds in a stepwise manner, beginning with hematopoietic stem cells, continuing to develop into various stages of progenitor cells, and finally becoming fully functional blood cells. As this process goes awry, immature, functionless cells of the myeloid lineage proliferate out of control. Discerning how myeloid progenitor frequency is regulated allows for a better understanding of how the process may lose control. Hematopoiesis has been shown to depend on genetic and environmental factors. In this work, I have added to this knowledge base by providing …

The Expression And Function Of Hypoxia Inducible Factor-1Α In Human Melanoma, Sandeep S. Joshi

Theses, Dissertations and Capstones

Hypoxia inducible factor-1α (HIF-1α) protein, a key regulator of oxygen homeostasis, is stabilized under hypoxia and degraded under normal oxygen tension. Here, the human melanoma cells were found to express an elevated amount of HIF-1α mRNA and protein relative to normal human melanocytes under normoxic conditions. The amount of HIF-1α expressed is roughly correlated with the stage of melanoma from which the cell line was established. In addition, a splice variant mRNA of HIF-1α785 is expressed at higher levels than full-length HIF-1α mRNA in the more aggressive melanoma cells. This splice variant lacks part of the oxygen regulation domain. Ectopic …

Pregnancy Associated Breast Cancer: An Analysis Of Fetal Treatment Risk, Melissa Barnett

The Science Journal of the Lander College of Arts and Sciences

There are several viable treatment options for patients with PABC considered un-harmful to fetal development. Trastusumab, or Herceptin, targets HER2 protein and successfully combats aggressive breast cancer. In standard doses, it appears to be safe to the fetus even when administered during the first trimester. A likely side effect of Herceptin is anhydramnios, which can be monitored for throughout the stages of a pregnancy (Shrim et al. 2008). Anthracyclines, commonly used in chemotherapy, appear to be non-toxic, and have been used to successfully cure PABC patients in their second and third trimester. However, first trimester spontaneous abortions are documented to …

2009 Cancer Care Annual Report, Children's Mercy Hospital

Cancer Center Annual Reports

Annual report of cancer care and oncology services at the Children's Mercy Hospital, Kansas City MO, a pediatric medical center. This report has a focus on acute lymphoblastic leukemia.

Role Of Intrathecal Rituximab And Trastuzumab In The Management Of Leptomeningeal Carcinomatosis, Anthony J. Perissinotti, David J. Reeves

Scholarship and Professional Work – COPHS

OBJECTIVE: To review evidence for the use of intrathecal rituximab and trastuzumab in the management of leptomeningeal carcinomatosis.

DATA SOURCES: A search of MEDLINE (1966-July 2010) and International Pharmaceutical Abstracts (1970-July 2010) was performed using search terms intrathecal, trastuzumab, rituximab, and monoclonal antibody. Additionally, American Society of Clinical Oncology, San Antonio Breast Conference, American Association for Cancer Research, and American Society of Hematology meeting abstracts were searched.

STUDY SELECTION AND DATA EXTRACTION: Publications were reviewed for inclusion. Those reporting use of rituximab and trastuzumab intrathecally are reviewed and include 1 Phase 1 trial, 2 small prospective studies, 1 case series, …

Sputum Neutrophils As A Biomarker In Copd: Findings From The Eclipse Study, Dave Singh, Lisa Edwards, Ruth Tal-Singer, Stephen I. Rennard

Journal Articles: Pulmonary & Critical Care Med

INTRODUCTION: The percentage of neutrophils in sputum are increased in COPD patients, and may therefore be a biomarker of airway inflammation. We studied the relationships between sputum neutrophils and FEV1, health status, exacerbation rates, systemic inflammation and emphysema, and long term variability at 1 year.

METHODS: Sputum samples were obtained from 488 COPD patients within the ECLIPSE cohort. 359 samples were obtained at baseline, and 297 after 1 year. 168 subjects provided samples at both visits. Serum interleukin-6 (IL-6), IL-8, surfactant protein D and C-reactive protein levels were measured by immunoassays. Low-dose CT scans evaluated emphysema.

RESULTS: Sputum neutrophil % …

The Peanut Allergy Epidemic, Rivky Sachs

The Science Journal of the Lander College of Arts and Sciences

Peanut allergy is one of the most predominant food allergies. It accounts for majority of the highly severe and fatal allergic reactions to food. Peanut allergy is generally detected early in life and is commonly associated with other atopic disorders such as asthma, eczema, and rhinitis. The prevalence and pervasiveness of peanut allergies is increasing worldwide, and most peanut allergic patients have lifelong sensitivities to peanuts (de Leon et al, 2008). Patients with severe allergies must stringently avoid any contact with peanuts and depend on intramuscular epinephrine (EpiPen) to counteract the reaction caused by intake of peanuts. Much research is …

Prieurianin Causes Weight Loss In Diet-Induced Obese Mice And Inhibits Adipogenesis In Cultured Preadipocytes, Ahmed Kablan, Rudel A. Saunders, Maria Szkudlarek-Mikho, Andrew J.B. Chin, Raul M. Bosio, Kazuyuki Fujii, Joseph I. Shapiro M.D., Khew-Voon Chin

Biochemistry and Microbiology

The global increase in the incidence of obesity has emerged as one of the most serious public health risks in recent years. Despite the enormity of the obesity pandemic, there are currently only two FDA-approved therapies for its treatment and these drugs exhibit modest effi cacy and have limiting side effects. Prieurianin is a plant limonoid product that deters feeding in insect larvae. We investigated in this study the effects of prieurianin on weight loss and adipogenesis. Our results showed that prieurianin causes weight loss by reducing energy intake in obese mice on highcalorie diet. We also found that prieurianin …

Adaptive Radiation Therapy Of Prostate Cancer, Ning Wen

Wayne State University Dissertations

ART is a close-loop feedback algorithm which evaluates the organ deformation and motion right before the treatment and takes into account dose delivery variation daily to compensate for the difference between planned and delivered dose. It also has potential to allow further dose escalation and margin reduction to improve the clinical outcome. This retrospective study evaluated ART for prostate cancer treatment and radiobiological consequences. An IRB approved protocol has been used to evaluate actual dose delivery of patients with prostate cancer undergoing treatment with daily CBCT.

The dose from CBCT was measured in phantom using TLD and ion chamber techniques …

Identification Of Neuroblastoma And Its Prognostic Markers Using Raman Spectroscopy, Rachel Kast

Wayne State University Dissertations

Introduction: Neuroblastoma is the most common cancer of infancy. It is one of several peripheral nervous system tumors, including ganglioneuroma, peripheral nerve sheath tumor, and pheochromocytoma. It is commonly situated on the adrenal gland. It displays similar histology to other small round blue cell tumors, including non-Hodgkin lymphoma, rhabdomyosarcoma, and Ewing sarcoma. One method of judging neuroblastoma aggressiveness uses tumor histology factors, including mitosis-karyorrhexis index, Schwannian stromal development, degree of differentiation, and patient age. Tumor aggressiveness can also be judged based on the amplification of certain genes, including MYCN. Raman spectroscopy is a physics-based method which identifies the biochemical …

Egfr/Met Association Regulates Egfr Tki Resistance In Breast Cancer, Kelly L. Mueller, Zeng-Quan Yang, Ramsi Haddad, Stephen P. Ethier, Julie L. Boerner

Wayne State University Associated BioMed Central Scholarship

Abstract

Breast cancers show a lack of response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), despite 30% of tumors expressing EGFR. The mechanism of this resistance is unknown; however, we have recently shown that Met kinase activity compensates for loss of EGFR kinase activity in cell culture models. Met has been implicated in the pathogenesis of breast tumors and therefore may cooperate with EGFR for tumor growth. Here we have found that EGFR phosphorylation and cell proliferation is in part regulated by Met expression. In addition, we found that Met constitutive phosphorylation occurred independent of the Met …

The Global Pediatrician: Is There Such A Person, Or Can There Be?, Robert Armstrong

Paediatrics and Child Health, East Africa

As pediatricians, our concern for the health of children and youth starts with our individual encounters with patients and their families and extends to the community in which they live and the broader systems of society that influence their health. This concept of a pediatrician is captured in one of the “bibles” of our profession and in the words of Richard Behrman when he defines pediatrics as being “concerned with the health of infants, children, and adolescents, their growth and development, and their opportunity to achieve full potential as adults.”¹ Health, growth and development, and opportunity as adults encompass …

Diverticular And Aneurysmal Structures Of The Left Ventricle In Adults: Report Of A Case Within The Context Of A Literature Review., Premraj Makkuni, Morris N Kotler, Vincent M. Figueredo

Department of Medical Genetics Faculty Papers

Left ventricular outpouchings are increasingly detected on cardiovascular imaging. Herein, we describe the case of a 45-year-old man who underwent noncardiac preoperative imaging and was found to have an asymptomatic left ventricular outpouching. The patient underwent successful surgical repair of the structure. When left ventricular outpouchings are detected, the main differential diagnoses are pseudoaneurysm, aneurysm, and diverticulum. The outcomes for these conditions differ substantially, and accurate diagnosis can be crucial in making clinical decisions. We review the relevant medical literature, outline the natural history of these left ventricular abnormalities, and discuss options in regard to their management.

Mechanism Of Catch Force: Tethering Of Thick And Thin Filaments By Twitchin., Thomas M Butler, Marion J Siegman

Department of Molecular Physiology and Biophysics Faculty Papers

Catch is a mechanical state occurring in some invertebrate smooth muscles characterized by high force maintenance and resistance to stretch during extremely slow relaxation. During catch, intracellular calcium is near basal concentration and myosin crossbridge cyctng rate is extremely slow. Catch force is relaxed by a protein kinase A-mediated phosphorylation of sites near the N- and C- temini of the minititin twitchin (approximately 526 kDa). Some catch force maintenance car also occur together with cycling myosin crossbridges at submaximal calcium concentrations, but not when the muscle is maximally activated. Additionally, the link responsible for catch can adjust during shortening of …

Differential Impact Of Tumor Suppressor Pathways On Dna Damage Response And Therapy-Induced Transformation In A Mouse Primary Cell Model., A Kathleen Mcclendon, Jeffry L Dean, Adam Ertel, Erik S Knudsen

Department of Cancer Biology Faculty Papers

The RB and p53 tumor suppressors are mediators of DNA damage response, and compound inactivation of RB and p53 is a common occurrence in human cancers. Surprisingly, their cooperation in DNA damage signaling in relation to tumorigenesis and therapeutic response remains enigmatic. In the context of individuals with heritable retinoblastoma, there is a predilection for secondary tumor development, which has been associated with the use of radiation-therapy to treat the primary tumor. Furthermore, while germline mutations of the p53 gene are critical drivers for cancer predisposition syndromes, it is postulated that extrinsic stresses play a major role in promoting varying …

Overview Of Surgical Management Of Infectious Non-Suppurative Brain Lesions (Part 2), Muhammad Shahzad Shamim, Ather Enam, Syed Faizan Ali, Rushna Pervez Ali, Mohammad Wasay

Section of Neurosurgery

No abstract provided.

Essential Medicines Management During Emergencies In Pakistan, S. K. S. Bukhari, J.A.R. H. Qureshi, Rashid Jooma, K.M. Bile, G. N. Kazi, W. A. Zaibi, A. Zafar

Section of Neurosurgery

This paper illustrates the experiences of essential medicine management in providing cure and care to victims of Pakistan's 2005 earthquake in a safe, rational and effective mode. The health interventions assured access to essential medicine, sustained supply, inventory control through a computerized logistic support system and rational use of medicines. World Health Organization Pakistan outlined modalities for acceptance of donated medicines, assisted in speedy procurement of medicines and designed customized kits. Proper storage of medicines at controlled temperature was ensured in warehousing facilities in 12 locations. A steady supply of medicines and their consumption without stock-outs in the 56 first-level …

Synergistic Effects Of Garcinol And Gemcitabine In Enhancing Therapeutic Efficacy In Pancreatic Adenocarcinoma Cells And Its Effect On Microrna Profile, Mansi Anand Parasramka

Wayne State University Dissertations

SYNERGISTIC EFFECTS OF GARCINOL AND GEMCITABINE IN ENHANCING THERAPEUTIC EFFICACY IN PANCREATIC ADENOCARCINOMA CELLS AND ITS EFFECT ON MICRORNA PROFILE

By

MANSI PARASRAMKA

ADVISOR: DR. SMITI V. GUPTA

MAJOR: NUTRITION AND FOOD SCIENCE

DEGREE: DOCTOR OF PHILOSPHY

Human Pancreatic Cancer (PaCa) is one of the most hostile and fourth leading cause of cancer deaths in the United States. Current standard chemotherapeutic agent for advanced PaCa is gemcitabine, a cytotoxic nucleoside analogue which results in modest response due to high degree of inherent and acquired chemo resistance. Forthcoming evidence strongly supports that non-nutritive food components have therapeutic benefits attributable to pleiotropic …

Role Of Transforming Growth Factor Beta In Corneal Function, Biology And Pathology, Ashish Tandon, Jonathan C. K. Tovey, Ajay Sharma, Rangan Gupta, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Transforming growth factor-beta (TGFβ) is a pleiotropic multifunctional cytokine that regulates several essential cellular processes in many parts of the body including the cornea. Three isoforms of TGFβ are known in mammals and the human cornea expresses all of them. TGFβ1 has been shown to play a central role in scar formation in adult corneas whereas TGFβ2 and TGFβ3 have been implicated to play a critical role in corneal development and scarless wound healing during embryogenesis. The biological effects of TGFβ in the cornea have been shown to follow SMAD dependent as well as SMAD-independent signaling pathways depending upon cellular …