Digital Commons Network^™

Targeting Apoptosis For Optical Imaging Of Infection, Mathew L Thakur, Kaijun Zhang, Bishnuhari Paudyal, Devadhas Devakumar, Maria Y Covarrubias, Changpo Cheng, Brian D Gray, Eric Wickstrom, Koon Y Pak

Department of Radiology Faculty Papers

PURPOSE: Infection is ubiquitous and a major cause of morbidity and mortality. The most reliable method for localizing infection requires radiolabeling autologous white blood cells ex vivo. A compound that can be injected directly into a patient and can selectively image infectious foci will eliminate the drawbacks. The resolution of infection is associated with neutrophil apoptosis and necrosis presenting phosphatidylserine (PS) on the neutrophil outer leaflet. Targeting PS with intravenous administration of a PS-specific, near-infrared (NIR) fluorophore will permit localization of infectious foci by optical imaging.

METHODS: Bacterial infection and sterile inflammation were induced in separate groups (n = 5) …

Response Of A Single 'Mega Intramuscular Dose' Of Vitamin D On Serum 25ohd And Parathyroid Hormone Levels, Aysha Habib, Dileep K Rohra, Shakil A Saghir, Shamsa K Udani, Richard Wood, Abdul Jabbar

Department of Pathology and Laboratory Medicine

Objective: To determine the changes produced in serum 25OHD and iPTH levels after 600,000 IU of injection cholecalciferol in volunteers. Study Design: Interventional study. Place and Duration of Study: Section of Chemical Pathology, Department of Pathology and Microbiology, the Aga Khan University Hospital, Karachi, from June 2009 - June 2010. Methodology: Volunteers of either gender aged 18-40 years with known 25OHD, calcium (Ca), creatinine (Cr) and phosphorous (P) levels were included in the study. Subjects on therapy like vitamin D and calcium supplements, corticosteroids or anti-epileptic medicines, primary hyperparathyroidism and hypercalcaemia, with co-morbidity like renal failure, liver disease and history …

Essential Role Of Caveolin-3 In Adiponectin Signalsome Formation And Adiponectin Cardioprotection., Yajing Wang, Xiaoliang Wang, Jean-François Jasmin, Wayne Bond Lau, Rong Li, Yuexin Yuan, Wei Yi, Kurt Chuprun, Michael P. Lisanti, Walter J Koch, Erhe Gao, Xin-Liang Ma

Department of Emergency Medicine Faculty Papers

OBJECTIVE: Adiponectin (APN) system malfunction is causatively related to increased cardiovascular morbidity/mortality in diabetic patients. The aim of the current study was to investigate molecular mechanisms responsible for APN transmembrane signaling and cardioprotection.

METHODS AND RESULTS: Compared with wild-type mice, caveolin-3 knockout (Cav-3KO) mice exhibited modestly increased myocardial ischemia/reperfusion injury (increased infarct size, apoptosis, and poorer cardiac function recovery; P

CONCLUSIONS: Taken together, these results demonstrated for the first time that Cav-3 plays an essential role in APN transmembrane signaling and APN anti-ischemic/cardioprotective actions.

Cosmetic Neurology: Enhancement Of The Mind And Attention Deficit Hyperactive Disorder Medication Abuse Among College Students, Mary M. Huff

Senior Honors Theses

Cosmetic neurology is becoming increasingly popular, and it is not just sleep deprived, over worked college students who are interested. People are beginning to seek off-label prescriptions for medications that are typically used to treat disorders such as attention deficit hyperactive disorder (ADHD) or narcolepsy, while researchers are trying to create drugs used solely for mind enhancement purposes. Along with these drugs come many legal and ethical quandaries relating to the regulation of current use as well as the what ifs of future possibilities. A survey was conducted among college students regarding the diagnosis of ADHD, the abuse of ADHD …

A Progressive Postresection Walking Program Significantly Improves Fatigue And Health-Related Quality Of Life In Pancreas And Periampullary Cancer Patients., Theresa Yeo, Sherry A Burrell, Patricia K Sauter, Eugene P Kennedy, Harish Lavu, Benjamin E Leiby, Charles Yeo

College of Nursing Faculty Papers & Presentations

BACKGROUND: As patients with pancreas and periampullary cancer (PPC) experience improved survival rates and longevity, the focus shifts toward living life while surviving cancer. Fatigue is the most commonly reported symptom in all cancer patients. Exercise has been found to effectively decrease fatigue levels and improve physical functioning in cancer patients.

STUDY DESIGN: One hundred two patients with resected PPC consented to participate in this study and were randomized to either an intervention group (IG) or a usual care group (UCG). Subjects completed visual analog scales, the FACIT-Fatigue Scale and the Short Form-36v2 after surgery and again 3 to 6 …

Randomized Controlled Trial Of Interferon Gamma Versus Amantadine In Combination With Interferon Alpha And Ribavirin For Hepatitis C Genotype 3 Non-Responders And Relapsers, Z Abbas, Sajjad Raza, Saeed Hamid, Wasim Jafri

Section of Gastroenterology

OBJECTIVES: To evaluate the efficacy and safety of triple combination regimens comprising of interferon alpha-2b (IFN-alpha) and ribavirin plus either IFN-gamma or amantadine in genotype 3 patients, responders or relapsers to interferon plus ribavirin combination.

METHODS: Patients were randomized to receive IFN-alpha 3MU thrice a week, ribavirin 800-1200 mg per day with either IFN-gamma 2 MU thrice a week or amantadine 100 mg twice daily. Treatment was continued for 48 weeks in patients showing complete or partial (2 log reduction) early virological response (EVR) at 12 weeks and negative PCR at 24 weeks.

RESULTS: Total enrollments were 44; 25 were …

Relationship Between Vitamin B12, Folate And Homocysteine Levels And H. Pylori Infection In Patients With Functional Dyspepsia: A Cross-Section Study, Shahid Rasool, Shahab Abid, Mohammad Perwaiz Iqbal, Naseema Mehboobali, Ghulam Haider, Wasim Jafri

Section of Gastroenterology

Background

H. pylori infection has been associated with many micronutrient deficiencies. There is a dearth of data from communities with nutritional deficiencies and high prevalence of H. pylori infection. The aim of this study was to determine the impact of H. pylori infection on serum levels of vitamin B₁₂, folate and homocysteine in patients with functional dyspepsia (FD).

Methods

One hundred and thirty-two patients with FD undergoing gastroscopy were enrolled. The serum was analyzed for B₁₂, folate and homocysteine levels before gastroscopy. H. pylori infection was diagnosed by histopathological examination of gastric biopsies and urea breath …

Expression Of Stem Cell Marker Aldh1 In Cervical Intraepithelial Neoplasia, Ping Gong, Juan Palazzo, Md

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Conclusions:

Cervical dysplasia show positive staining for ALDH1 compared to normal cervical mucosa.

ALDH1 positive cells distribution parallels the dysplastic cells in cervical dysplasia.

CSC, as detected by ALDH1 expression, may play a role in the progression of cervical intraepithelial neoplasia and carcinogenesis.

Aberrant Expression Of Cd56 On Granulocytes And Monocytes In Myeloproliferative Neoplasm And Myelodysplastic Syndrome, Ping Gong, Md, Fernanco Metrebian, Md, Alina Dulau-Florea, Md, Zi-Xuan Wang, Phd, Renu Bajaj, Phd, Stephen C Peiper, Jerald Z. Gong, Md

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Conclusions:

Aberrant CD56 expression on granulocytes is seen in all aubtypes MPN and high grade MDS. CD56 expression in MPN correlated with bone marrow morphology, BCR/ABL transcript, and bone marrow engraftment study following treatment. Identification of abnormal CD56+ granulocytes and monocytes is helpful in both the initial diagnosis and long-term follow up of patients with MPN and MDS.

Loss Of Retinoblastoma (Rb) Tumor Suppressor Expression In Breast Cancer Correlates With Better Response To Neoadjuvant Chemotherapy, Jeanne Mcfalls, Md, Jessica Kline, Ba, Gordon Schwartz, Md, Mba, Facs, Angieszka Witkiewicz, Md

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Conclusions:

Loss of RB tumor suppressor staining in pre-treatment breast cancer biopsies can be used prior to initiation of neoadjuvant chemotherapy to predict good tumor response. This association between RB loss and good neoadjuvant response holds regardless of ER status and across various chemotherapy regimens. Assessment of RB status in the pre-treatment biopsy could be useful clinical tool to define patients who are most likely to benefit from neoadjuvant chemotherapy.

P53 Expression In Oropharyngeal Squamous Cell Carcinoma In Increased In Hpv Positive Smokers, Madalina Tuluc, Voichita Bar-Ad, Zi-Xuan Wang, Joseph Curry

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background and Objectives

High risk HPV is associated with oropharyngeal SCC (OSCC) and is responsible for the increasing incidence of this cancer type among younger patients.

Patients with HPV positive oropharyngeal SCC have a better prognosis when compared with HPV negative, tobacco induced SCC.

HPV E6 inactivates p53 leading to low expression of p53; tobacco induced oropharyngeal SCC is characterized by p53 overexpression, resistance to treatment and poor prognosis. However, in many cases of HPV OSCC, there is a history of current or remote smoking, making this disease a multifactorial process. We expect that smoking will influence the level of …

P16/Rb Correlations In Oropharyngeal Squamous Cell Carcinoma (Oscc), Madalina Tuluc, Voichita Bar-Ad, David Cognetti

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The objective of this study is to explore the patterns of Rb expression in p16 positive and negative OSCC, in relation to patient's smoking history.

Alternative Therapy And Treatment Of Type 2 Diabetes, Carmine R. Grieco

Human Movement Studies & Special Education Theses & Dissertations

The rise in prevalence and incidence of type 2 diabetes mellitus (T2D) in the developing world continues unabated. Current treatment strategies, however, fall short of achieving optimal glycemic control. The aim of project I was to investigate the effect of an acute bout of a yogic breathing exercise on heart rate variability (HRV) in individuals with T2D. Project II was designed to assess the effectiveness of the neurohormone melatonin in lowering short- and long-term glucose levels, lipids and oxidative stress in T2D. Project III investigated the differential effects of two different styles of aerobic exercise on postprandial glycemia, mood and …

Synergistic Effect Of Subnanosecond Pulsed Electric Fields And Temperature On The Viability Of Biological Cells, James Thomas Camp

Electrical & Computer Engineering Theses & Dissertations

Pulsed electric fields have been used to induce a biological response in cells, and at sufficient energy, can cause cell death. By reducing the pulse duration from presently used nanosecond to subnanosecond ranges, the electric field can be delivered to biological tissue non-invasively by the use of an antenna instead of electrodes, such as needles. Studies have previously been completed in which the aim was to determine the energy density (electric field strength, number of pulses) required to induce cell death with 800 ps pulses. Based on this data, it was concluded that for pulse durations of 200 ps, with …

Role Of Poly [Adp-Ribose] Polymerase 1 In Retroviral Infection, Vanessa E. Rodriguez ^, Manuel Llano *

COURI Symposium Abstracts, Spring 2012

No abstract provided.

Characterization Of Species C Human Adenovirus Serotype 6 (Ad6), Eric A. Weaver, Reeti Khare, Mathew L. Hillestad, Donna Palmer, Philip Ng, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Adenovirus serotype (Ad5) is the most studied Ad. Ad1, 2, and 6 are also members of species C Ad and are presumed to have biologies similar to Ad5. In this work, we have compared the ability of Ad1, 2, 5, and 6 to infect liver and muscle after intravenous and intramuscular injection. We found that Ad6 was surprisingly the most potent at liver gene delivery and that Ad1 and Ad2 were markedly weaker than Ad5 and 6. To understand these differences, we sequenced the Ad6 genome. This revealed that the Ad6 fiber protein is surprisingly three shaft repeats shorter than …

A Role For Caveolin-1 In Desmoglein Binding And Desmosome Dynamics., D Brennan, S Peltonen, A Dowling, W Medhat, K J Green, J K Wahl, F Del Galdo, M G Mahoney

Department of Dermatology and Cutaneous Biology Faculty Papers

Desmoglein-2 (Dsg2) is a desmosomal cadherin that is aberrantly expressed in human skin carcinomas. In addition to its well-known role in mediating intercellular desmosomal adhesion, Dsg2 regulates mitogenic signaling that may promote cancer development and progression. However, the mechanisms by which Dsg2 activates these signaling pathways and the relative contribution of its signaling and adhesion functions in tumor progression are poorly understood. In this study we show that Dsg2 associates with caveolin-1 (Cav-1), the major protein of specialized membrane microdomains called caveolae, which functions in both membrane protein turnover and intracellular signaling. Sequence analysis revealed that Dsg2 contains a putative …

Heme Oxygenase-1 Regulates The Immune Response To Influenza Virus Infection And Vaccination In Aged Mice, Nathan W. Cummins, Eric A. Weaver, Shannon M. May, Anthony J. Croatt, Oded Foreman, Richard B. Kennedy, Gregory A. Poland, Michael A. Barry, Karl A. Nath, Andrew D. Badley

Nebraska Center for Virology: Faculty Publications

Underlying mechanisms of individual variation in severity of influenza infection and response to vaccination are poorly understood. We investigated the effect of reduced heme oxygenase-1 (HO-1) expression on vaccine response and outcome of influenza infection. HO-1-deficient and wild-type (WT) mice (kingdom, Animalia; phylum, Chordata; genus/species, Mus musculus) were infected with influenza virus A/PR/8/34 with or without prior vaccination with an adenoviral-based influenza vaccine. A genome-wide association study evaluated the expression of single-nucleotide polymorphisms (SNPs) in the HO-1 gene and the response to influenza vaccination in healthy humans. HO-1-deficient mice had decreased survival after influenza infection compared to WT mice (median …

Advances In Ultrafast Time Resolved Fluorescence Physics For Cancer Detection In Optical Biopsy, R. R. Alfano

Publications and Research

We discuss the use of time resolved fluorescence spectroscopy to extract fundamental kinetic information on molecular species in tissues. The temporal profiles reveal the lifetime and amplitudes associated with key active molecules distinguishing the local spectral environment of tissues. The femtosecond laser pulses at 310 nm excite the tissue. The emission profile at 340 nm from tryptophan is non-exponential due to the micro-environment. The slow and fast amplitudes and lifetimes of emission profiles reveal that cancer and normal states can be distinguished. Time resolved optical methods offer a new cancer diagnostic modality for the medical community.

Inhibition Of Fatty Acid Synthase Attenuates Cd44-Associated Signaling And Reduces Metastasis In Colorectal Cancer, Yekaterina Y. Zaytseva, Piotr G. Rychahou, Pat Gulhati, Victoria Allison Elliott, William Conan Mustain, Kathleen O'Connor, Andrew J. Morris, Manjula Sunkara, Heidi L. Weiss, Eun Young Lee, B. Mark Evers

Markey Cancer Center Faculty Publications

Fatty acid synthase (FASN) and ATP-citrate lyase, key enzymes of de novo lipogenesis, are significantly upregulated and activated in many cancers and portend poor prognosis. Even though the role of lipogenesis in providing proliferative and survival advantages to cancer cells has been described, the impact of aberrant activation of lipogenic enzymes on cancer progression remains unknown. In this study, we found that elevated expression of FASN is associated with advanced stages of colorectal cancer (CRC) and liver metastasis, suggesting that it may play a role in progression of CRC to metastatic disease. Targeted inhibition of lipogenic enzymes abolished expression of …

Increase In Muscle Mitochondrial Biogenesis Does Not Prevent Muscle Loss But Increased Tumor Size In A Mouse Model Of Acute Cancer-Induced Cachexia., Xiao Wang, Alicia M Pickrell, Teresa A Zimmers, Carlos T Moraes

Kimmel Cancer Center Faculty Papers

Cancer-associated cachexia is a complex metabolic condition characterized by the progressive loss of body fat and deterioration of muscle mass. Although the cellular and molecular mechanisms of cachexia are incompletely understood, previous studies have suggested mitochondrial dysfunction in murine models of cancer cachexia. To better understand the metabolic shift in cancer-induced cachexia, we studied the effects of enhanced oxidative capacity on muscle wasting using transgenic mice over-expressing Peroxisome Proliferator-Activated Receptor gamma Co-activator-1α (PGC-1α) in skeletal muscle in a Lewis lung carcinoma-implanted model. Increased mitochondrial biogenesis was observed in the skeletal muscle of tumor-implanted mice. However, these increases did not prevent …

Differential Analysis Of Ovarian And Endometrial Cancers Identifies A Methylator Phenotype, Diana L. Kolbe, Julie A. Deloia, Patricia Porter-Gill, Mary Strange, Hanna M. Petrykowska, Alfred Guirguis, Thomas C. Krivak, Lawrence C. Brody, Laura Elnitski

Exercise and Nutrition Sciences Faculty Publications

Despite improved outcomes in the past 30 years, less than half of all women diagnosed with epithelial ovarian cancer live five years beyond their diagnosis. Although typically treated as a single disease, epithelial ovarian cancer includes several distinct histological subtypes, such as papillary serous and endometrioid carcinomas. To address whether the morphological differences seen in these carcinomas represent distinct characteristics at the molecular level we analyzed DNA methylation patterns in 11 papillary serous tumors, 9 endometrioid ovarian tumors, 4 normal fallopian tube samples and 6 normal endometrial tissues, plus 8 normal fallopian tube and 4 serous samples from TCGA. For …

Inverse Relationship Between Psa And Il-8 In Prostate Cancer: An Insight Into A Nf-Κb-Mediated Mechanism, Yong Xu, Daret K. St. Clair, Fang Fang, William H. St. Clair

Toxicology and Cancer Biology Faculty Publications

Background: Prostate specific antigen (PSA) is traditionally used as an indicator for the presence of prostate cancer (PCa) and radiotherapy is generally used to treat inoperable and locally advanced PCa. However, how cellular PSA level is associated with sensitivity of PCa to radiotherapy is unknown. The previous finding that the RelB-based NF-κB alternative pathway differentially regulates PSA and interleukin-8 (IL-8) in aggressive PCa has directed our attention to the role of RelB in the response of PCa to radiotherapy.

Methodology/Principal Findings: RelB and its targets PSA and IL-8 in PCa cells were manipulated by ectopic expression in PCa …

Inhibition Of Adhesion And Invasion Of Pseudomonas Aeruginosa To Lung Epithelial Cells: A Model Of Cystic Fibrosis Infection, Ayman Noreddin, Ghada Sawy, Walid Elkhatib, Ehab Noreddin, Atef Shibl

Pharmacy Faculty Books and Book Chapters

"Over their life time, CF patients experience multiple infections by various pneumoniacausing bacteria [6]. With more patients surviving to adulthood, chronic infections with Pseudomonas aeruginosa are coming to the forefront as a leading cause of death [7]. Problems presented by infected CF lung are multi-dimensional; the electrolyte balance and pH of the fluids are abnormal. The mucus is thick and of an alternative composition compared to normal lung and may contribute to colonization with Pseudomonas aeruginosa [2, 3, 5]. As such, research is multi-pronged and includes gene therapy to correct the defective protein, amelioration of inflammatory response and thinning of …

Recommendations For The Use Of Common Outcome Measures In Pediatric Traumatic Brain Injury Research, Stephen R. Mccauley, Elisabeth A. Wilde, Vicki A. Anderson, Gary Bedell, Sue R. Beers, Thomas F. Campbell, Sandra B. Chapman, Linda Ewing-Cobbs, Joan P. Gerring, Gerard A. Gioia, Harvey S. Levin, Linda J. Michaud, Mary R. Prasad, Bonnie R. Swaine, Lyn S. Turkstra, Shari L. Wade, Keith O. Yeates

Psychiatry and Behavioral Sciences Faculty Publications

This article addresses the need for age-relevant outcome measures for traumatic brain injury (TBI) research and summarizes the recommendations by the inter-agency Pediatric TBI Outcomes Workgroup. The Pediatric Workgroup's recommendations address primary clinical research objectives including characterizing course of recovery from TBI, prediction of later outcome, measurement of treatment effects, and comparison of outcomes across studies. Consistent with other Common Data Elements (CDE) Workgroups, the Pediatric TBI Outcomes Workgroup adopted the standard three-tier system in its selection of measures. In the first tier, core measures included valid, robust, and widely applicable outcome measures with proven utility in pediatric TBI from …

Medical Education Digest, Vol. 14 No. 2 (March/April 2012), Nova Southeastern University

Medical Education Digest

No abstract provided.

Outer Space And Oocyte Developmental Competence., Andrew J Watson

Obstetrics & Gynaecology Publications

No abstract provided.

Conformational Melding Permits A Conserved Binding Geometry In Tcr Recognition Of Foreign And Self Molecular Mimics, Oleg Y. Borbulevych, Kurt H. Piepenbrink, Brian M. Baker

Food for Health: Publications

Molecular mimicry between foreign and self antigens is a mechanism of T cell receptor cross reactivity and is thought to contribute to the development of autoimmunity. The αβ TCR A6 recognizes the foreign antigen Tax from the virus HTLV-1 when presented by the class I MHC HLA-A2. In a possible link with the autoimmune disease HAM/TSP, A6 also recognizes a self peptide from the neuronal protein HuD in the context of HLA-A2. We found here that the complexes of the HuD and Tax epitopes with HLA-A2 are close but imperfect structural mimics, and that in contrast with other recent structures …

Cyclin D1 Induces Chromosomal Instability., Mathew C Casimiro, Richard Pestell

Department of Cancer Biology Faculty Papers

We developed mouse model systems to investigate the potential for cyclin D1 to induce CIN in vivo. In a mammary gland specific Tet-inducible model the acute expression profile regulated by cyclin D1 after 7 days was enriched in genes that rank highly with CIN. We also used a mammary gland targeted model (MMTV) to continuously express cyclin D1. The mice started to develop mammary gland tumors at 400 days and the tumor-free incidence was 40% in MMTV-cyclin D1. The gene expression profile of the tumors showed enrichment for the CIN signature. We next compared cyclin D1 expression and the highest …

Small Non-Coding Rnas Govern Mammary Gland Tumorigenesis., Zuoren Yu, Richard Pestell

Department of Cancer Biology Faculty Papers

Small non-coding RNAs include siRNA, miRNA, piRNA and snoRNA. The involvement of miRNAs in the regulation of mammary gland tumorigenesis has been widely studied while the role for other small non-coding RNAs remains unclear. Here we summarize the involvement of miRNA in breast cancer onset and progression through regulating the cell cycle and cellular proliferation. The regulation of breast cancer stem cells and tumor regeneration by miRNA is reviewed. In addition, the emerging evidence demonstrating the involvement of piRNA and snoRNA in breast cancer is briefly described.