Digital Commons Network^™

Pipkiγ Regulates Focal Adhesion Dynamics And Colon Cancer Cell Invasion, Zhaofei Wu, Xiang Li, Manjula Sunkara, Heather Spearman, Andrew J. Morris, Cai Huang

Markey Cancer Center Faculty Publications

Focal adhesion assembly and disassembly are essential for cell migration and cancer invasion, but the detailed molecular mechanisms regulating these processes remain to be elucidated. Phosphatidylinositol phosphate kinase type Iγ (PIPKIγ) binds talin and is required for focal adhesion formation in EGF-stimulated cells, but its role in regulating focal adhesion dynamics and cancer invasion is poorly understood. We show here that overexpression of PIPKIγ promoted focal adhesion formation, whereas cells expressing either PIPKIγ^K188,200R or PIPKIγ^D316K, two kinase-dead mutants, had much fewer focal adhesions than those expressing WT PIPKIγ in CHO-K1 cells and HCT116 colon cancer cells. Furthermore, …

Activation Of Matrix Metalloproteinases Following Anti-Aβ Immunotherapy; Implications For Microhemorrhage Occurrence, Donna M. Wilcock, Dave Morgan, Marcia N. Gordon, Tiffany L. Taylor, Lisa A. Ridnour, David A. Wink, Carol A. Colton

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Anti-Aβ immunotherapy is a promising approach to the prevention and treatment of Alzheimer's disease (AD) currently in clinical trials. There is extensive evidence, both in mice and humans that a significant adverse event is the occurrence of microhemorrhages. Also, vasogenic edema was reported in phase 2 of a passive immunization clinical trial. In order to overcome these vascular adverse effects it is critical that we understand the mechanism(s) by which they occur.

METHODS: We have examined the matrix metalloproteinase (MMP) protein degradation system in two previously published anti-Aβ immunotherapy studies. The first was a passive immunization study in which …

Bioluminescent Imaging Reveals Divergent Viral Pathogenesis In Two Strains Of Stat1-Deficient Mice, And In Αßγ Interferon Receptor-Deficient Mice, Tracy Jo Pasieka, Lynne Collins, Megan A. O'Connor, Yufei Chen, Zachary M. Parker, Brent L. Berwin, David R. Piwnica-Worms, David A. Leib

Dartmouth Scholarship

Pivotal components of the IFN response to virus infection include the IFN receptors (IFNR), and the downstream factorsignal transducer and activator of transcription 1 (Stat1). Mice deficient for Stat1 and IFNR (Stat12/2 and IFNaßcR2/2 mice) lack responsiveness to IFN and exhibit high sensitivity to various pathogens. Here we examined herpes simplex virus type 1 (HSV-1) pathogenesis in Stat12/2 mice and in IFNaßcR2/2 mice following corneal infection and bioluminescent imaging. Two divergent and paradoxical patterns of infection were observed. Mice with an N-terminal deletion in Stat1 (129Stat12/2(N-term)) had transient infection of the liver and spleen, but succumbed to encephalitis by day …

John H. Gibbon, Jr., M.D.: Surgical Innovator, Pioneer, And Inspiration., Jordan P. Bloom, B.S., Charles J. Yeo, Md, Herbert E. Cohn, Md, Pinckney J. Maxwell, Iv, Md

Department of Surgery Gibbon Society Historical Profiles

Throughout history there have been many discoveries that have changed the world, including Albert Einstein’s theory of relativity, Alexander Graham Bell’s telephone, and Jack Kilby and Robert Noyce’s microchip. There are a few analogous contributions that have been made in medicine: Sir Alexander’s discovery of penicillin, Lister’s principles of antiseptic technique, Salk and Sabin’s vaccines for polio, as well as numerous others. These innovative thinkers all had two factors in common. First, they were pioneers who faced problems that had no solutions at the time and who refused to accept the status quo in the face of great scrutiny and …

An Occupational-Based Experimental Study Of Collective Vs. Personal Efficacy To Encourage Sun Protective Behaviors In Head Start Preschool Teachers, Elizabeth A. Holzhauser

Loma Linda University Electronic Theses, Dissertations & Projects

Background. Skin cancer is one of the most common types of cancers in the United States. An analysis of literature shows that skin cancer can be partially mitigated through personal behavior changes (Glanz, Buller, & Saraiya; 2007, Canadian Centre of Occupational Health and Safety [CCOHS], 2010). Currently national sun-safety educational campaigns promote sun-protective behaviors to individuals who receive exposure due to their work environment (Task Force on Community Preventive Services, 2004). Preschool teachers employed with San Bernardino County Head Start are inadvertently exposed to sunlight during mandatory recess periods posing risks to their health.

Purpose. This study evaluated two instructional …

Identification Of A Mechanism For Increased Cardiovascular Risk Among Individuals With Low Vitamin D Concentrations., Peter F Schnatz, Matthew Nudy, David M O'Sullivan, Kelly Ethun, Susan E Appt, Thomas B Clarkson

Department of Obstetrics and Gynecology Faculty Papers

OBJECTIVE: The aim of this study was to investigate the plasma concentrations of vitamin D and its association with plasma lipid profiles.

METHODS: Plasma vitamin D3 and lipid concentrations were measured in 119 female cynomolgus monkeys (premenopausal, n = 49; ovariectomized, n = 70) consuming approximately 1,000 IU per day of vitamin D3. In a subset of the ovariectomized monkeys (n = 23), vitamin D3 was remeasured after 6 months. The concentrations of vitamin D3 were analyzed as a continuous variable and were divided at the median into high (≥48 ng/mL) versus low (<48 ng>/mL) groupings.

RESULTS: Among the 119 …

Effectiveness Of Neuromuscular Conditioning To Prevent Anterior Cruciate Ligament Injuries In Female Athletes: A Critical Synthesis Of Literature, Shiren G. Assaly, Todd E. Davenport, Katrin Mattern-Baxter

School of Pharmacy Faculty Articles

Background and Purpose: Anterior cruciate ligament (ACL) injuries are common among female athletes. The purpose of this literature review was to assess the effectiveness of neuromuscular conditioning to modify biomechanical risk factors for ACL injury.

METHOD: A structured literature search was conducted to identify primary research articles. Articles were graded according to their strength of evidence and a qualitative literature review was completed.

RESULTS: Seven primary research studies were available for analysis that documented the effects of neuromuscular conditioning (range of evidence grades: 1B to 3B). Lower limb kinematics, lower limb kinetics, and incidence of tears were the primary outcomes …

Isolated Cryptococcal Osteomyelitis In An Immunocompetent Patient, Irfan Qadir, Farheen Ali, Umair Zafar Malik, Masood Umer

Department of Surgery Docs

bstract

Cryptococcosis is a rare infection in HIV-negative individuals. While the lungs and the central nervous system are most commonly infected, skeletal cryptococcosis is uncommon and isolated osteomyelitis due to Cryptococcus neoformans is quite rare. To our knowledge, only 47 cases of isolated cryptococcal osteomyelitis have been reported from 1974 to 2005. We report a case of isolatedcryptococcal osteomyelitis in an immunocompetent patient, who received 12 weeks of fluconazole with complete recovery.

Setting Research Priorities To Reduce Global Mortality From Childhood Pneumonia By 2015, Igor Rudan, Shams El Arifeen, Zulfiqar Ahmed Bhutta, Robert E. Black, Abdullah Brooks, Kit Yee Chan, Mickey Chopra, Trevor Duke, David Marsh, Antonio Pio, Eric A. F. Simoes, Giorgio Tamburlini, Evropi Theodoratou, Martin W. Weber, Cynthia G. Whitney, Harry Campbell, Shamim A. Qazi

Department of Paediatrics and Child Health

No abstract provided.

Ccr3 Inhibition For Ocular Angiogenesis And Macular Degeneration, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Patents

Provided are methods and compositions for the treatment or prevention of ocular angiogenesis and neovascularization. Administration of inhibitors of the CCR3 receptor or its ligands eotaxin (CCL11), eotaxin-2 (CCL24) or eotaxin-3 (CCL26) inhibits ocular angiogenesis.

Evaluation Of The Global Association Between Cholesterol-Associated Polymorphisms And Alzheimer's Disease Suggests A Role For Rs3846662 And Hmgcr Splicing In Disease Risk, Christopher R. Simmons, Fanggeng Zou, Steven G Younkin, Steven Estus

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Recent genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNP)s that are essentially unequivocally associated with peripheral cholesterol. Since the alleles of the APOE gene, which modulate peripheral cholesterol metabolism, and midlife plasma cholesterol are both associated with Alzheimer's disease (AD) risk, we have evaluated the hypothesis that SNPs associated with plasma cholesterol are also associated with AD.

RESULTS: Seventeen non-APOE SNPs reproducibly associated with cholesterol per GWAS were tested for association with AD in ~2,000 AD and ~4,000 non-AD subjects. As a group, these SNPs are associated with AD. Two SNPs in particular, rs3846662 and rs1532085, are …

Critical Role Of Pi3k/Akt/Gsk3Β In Motoneuron Specification From Human Neural Stem Cells In Response To Fgf2 And Egf, Luis Ojeda, Junling Gao, Kristopher G. Hooten, Enyin Wang, Jason R. Thonhoff, Tiffany J. Dunn, Tianyan Gao, Ping Wu

Markey Cancer Center Faculty Publications

Fibroblast growth factor (FGF) and epidermal growth factor (EGF) are critical for the development of the nervous system. We previously discovered that FGF2 and EGF had opposite effects on motor neuron differentiation from human fetal neural stem cells (hNSCs), but the underlying mechanisms remain unclear. Here, we show that FGF2 and EGF differentially affect the temporal patterns of Akt and glycogen synthase kinase 3 beta (GSK3β) activation. High levels of phosphatidylinositol 3-kinase (PI3K)/Akt activation accompanied with GSK3β inactivation result in reduction of the motor neuron transcription factor HB9. Inhibition of PI3K/Akt by chemical inhibitors or RNA interference or overexpression of …

Perfluorochemical Liquid-Adenovirus Suspensions Enhance Gene Delivery To The Distal Lung., Jeffrey A Kazzaz, Marlene S Strayer, Jichuan Wu, Daniel J Malone, Hshi-Chi Koo, Thomas H Shaffer, Jonathan M Davis, David S Strayer, Marla R Wolfson

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

WE COMPARED LUNG DELIVERY METHODS OF RECOMBINANT ADENOVIRUS (RAD): (1) rAd suspended in saline, (2) rAd suspended in saline followed by a pulse-chase of a perfluorochemical (PFC) liquid mixture, and (3) a PFC-rAd suspension. Cell uptake, distribution, and temporal expression of rAd were examined using A549 cells, a murine model using luciferase bioluminescence, and histological analyses. Relative to saline, a 4X increase in transduction efficiency was observed in A549 cells exposed to PFC-rAd for 2-4 h. rAd transgene expression was improved in alveolar epithelial cells, and the level and distribution of luciferase expression when delivered in PFC-rAd suspensions consistently peaked …

Letters To The Editor

Jefferson Journal of Psychiatry

Letters to the Editor for the Jefferson Journal of Psychiatry, Volume 3, Number 2, July 1985.

A Conserved Tissue-Specific Homeodomain-Less Isoform Of Meis1 Is Downregulated In Colorectal Cancer., Richard C Crist, Jacquelyn J Roth, Scott A Waldman, Arthur M Buchberg

Department of Microbiology and Immunology Faculty Papers

Colorectal cancer is one of the most common cancers in developed nations and is the result of both environmental and genetic factors. Many of the genetic lesions observed in colorectal cancer alter expression of homeobox genes, which encode homeodomain transcription factors. The MEIS1 homeobox gene is known to be involved in several hematological malignancies and solid tumors and recent evidence suggests that expression of the MEIS1 transcript is altered in colorectal cancer. Despite this potential connection, little is known about the role of the gene in the intestines. We probed murine gastrointestinal tissue samples with an N-terminal Meis1 antibody, revealing …

Cell Migration Dynamics After Alteration Of Cell-Cell Contacts In Fibrosarcoma And Glioblastoma Cell Lines, Hassan S. Rizvi, Ronald K. Gary

Undergraduate Research Opportunities Program (UROP)

Cell migration is a vital component of metastasis. In this study, our intent was to study cell migration by alteration of the Wnt/GSK-3 Pathway. Since BeSO4 is a known GSK-3 kinase inhibitor, we hypothesized that this agent would cause cell migration to decrease as a result of β-catenin stabilization. Two human cell lines, HT-1080 (fibrosarcoma) and A172 (glioblastoma), were used to observe migration levels in the presence and absence of BeSO4. Our results show that cell migration is diminished for cells that were pre-treated with BeSO4, in comparison to the untreated (control) cells.

Tlr4 Mutation Reduces Microglial Activation, Increases Aβ Deposits And Exacerbates Cognitive Deficits In A Mouse Model Of Alzheimer's Disease, Min Song, Jingji Jin, Jinghong Kou, Abhinandan Pattanayak, Jamaal Rehman, Hong-Duck Kim, Ken-Ichiro Fukuchi

NYMC Faculty Publications

BACKGROUND: Amyloid plaques, a pathological hallmark of Alzheimer's disease (AD), are accompanied by activated microglia. The role of activated microglia in the pathogenesis of AD remains controversial: either clearing Aβ deposits by phagocytosis or releasing proinflammatory cytokines and cytotoxic substances. Microglia can be activated via toll-like receptors (TLRs), a class of pattern-recognition receptors in the innate immune system. We previously demonstrated that an AD mouse model homozygous for a loss-of-function mutation of TLR4 had increases in Aβ deposits and buffer-soluble Aβ in the brain as compared with a TLR4 wild-type AD mouse model at 14-16 months of age. However, it …

Protein Kinase Cδ And C-Abl Kinase Are Required For Transforming Growth Factor Β Induction Of Endothelial-Mesenchymal Transition In Vitro., Zhaodong Li, Sergio A. Jimenez

Department of Medicine Faculty Papers

OBJECTIVE: The origin of the mesenchymal cells responsible for the intimal fibrosis in systemic sclerosis (SSc) has not been fully identified. The present study was undertaken to investigate whether subendothelial mesenchymal cells may emerge through transdifferentiation of endothelial cells (ECs) into myofibroblasts via endothelial-mesenchymal transition (EndoMT) in vitro and to explore the signaling pathways involved in this process.

METHODS: Primary mouse pulmonary ECs isolated by immunomagnetic methods with sequential anti-CD34 and anti-CD102 antibody selection were cultured in monolayers. Cell morphology and diacetylated low-density lipoprotein uptake assays confirmed their EC characteristics. The induction of EndoMT was assessed by determination of α-smooth …

Sub Total Aortic Replacement Using Simultaneous Bentall And Elephant Trunk Procedure, Mehreen Kisat, Umer Darr

Section of Cardiothoracic Surgery

A 22 year old female with valvular heart disease, moderate mitral valve insufficiency, moderate aortic insufficiency, extensive aneurysmal dilatation of the entire ascending aorta and arch, and segmental dilatation of descending aorta underwent entire anterior aortic replacement. We performed aortic root and valve replacement with a composite graft, followed by coronary artery reimplantation using the Bentall and De Bono technique. Simultaneously, we carried out a graft replacement of the transverse arch and descending aortic aneurysms with a woven Dacron graft using the Elephant Trunk technique. The goal of this surgery was to correct or optimally treat the multiple sites of …

In-Vivo Ct Dosimetry During Virtual Colonoscopy, Jonathon W. Mueller

Dissertations and Theses (Open Access)

Virtual colonoscopy (VC) is a minimally invasive means for identifying colorectal polyps and colorectal lesions by insufflating a patient’s bowel, applying contrast agent via rectal catheter, and performing multi-detector computed tomography (MDCT) scans. The technique is recommended for colonic health screening by the American Cancer Society but not funded by the Centers for Medicare and Medicaid Services (CMS) partially because of potential risks from radiation exposure. To date, no in‐vivo organ dose measurements have been performed for MDCT scans; thus, the accuracy of any current dose estimates is currently unknown.

In this study, two TLDs were affixed to the inner …

The Role Of Acidic Fibroblast Growth Factor And Fibroblast Growth Factor Receptor 4 In High Grade Serous Carcinoma, Tarrik Zaid

Dissertations and Theses (Open Access)

Background: High grade serous carcinoma whether ovarian, tubal or primary peritoneal, continues to be the most lethal gynecologic malignancy in the USA. Although combination chemotherapy and aggressive surgical resection has improved survival in the past decade the majority of patients still succumb to chemo-resistant disease recurrence. It has recently been reported that amplification of 5q31-5q35.3 is associated with poor prognosis in patients with high grade serous ovarian carcinoma. Although the amplicon contains over 50 genes, it is notable for the presence of several members of the fibroblast growth factor signaling axis. In particular acidic fibroblast growth factor (FGF1) …

The Development And Implementation Of An Anthropomorphic Head Phantom For The Assessment Of Proton Therapy Treatment Procedures, Paige A. Summers

Dissertations and Theses (Open Access)

Proton therapy has become an increasingly more common method of radiation therapy, with the dose sparing to distal tissue making it an appealing option, particularly for treatment of brain tumors. This study sought to develop a head phantom for the Radiological Physics Center (RPC), the first to be used for credentialing of institutions wishing to participate in clinical trials involving brain tumor treatment of proton therapy. It was hypothesized that a head phantom could be created for the evaluation of proton therapy treatment procedures (treatment simulation, planning, and delivery) to assure agreement between the measured dose and calculated dose within …

Polycyclic Aromatic Hydrocarbons In Maternal And Umbilical Cord Blood From Pregnant Hispanic Women Living In Brownsville, Texas, Ken Sexton, Jennifer J Salinas, Thomas J Mcdonald, Rose M Z Gowen, Rebecca P Miller, Joseph B Mccormick, Susan P Fisher-Hoch

Faculty, Staff and Student Publications

Venous blood was drawn from 35 pregnant Hispanic women living in Brownsville, Texas, and matched cord blood was collected at birth. Gas chromatography/mass spectrometry was used to measure concentrations of 55 individual PAHs or groups of PAHs. Results indicate that these women and their fetuses were regularly exposed to multiple PAHs at comparatively low concentrations, with levels in cord blood generally exceeding levels in paired maternal blood. While the possibility of related adverse effects on the fetus is uncertain, these exposures in combination with socioeconomically-disadvantaged and environmentally-challenging living conditions raise legitimate public health concerns.

Protection And Attachment Of Vibrio Cholerae Mediated By The Toxin-Coregulated Pilus In The Infant Mouse Model, Shelly J. Krebs, Ronald K. Taylor

Dartmouth Scholarship

Colonization of the human small intestine by Vibrio cholerae is an essential step in pathogenesis that requires the type IV toxin-coregulated pilus (TCP). To date, three functions of TCP have been characterized: it serves as the CTXΦ receptor, secretes the colonization factor TcpF, and functions in microcolony formation by mediating bacterium-bacterium interactions. Although type IV pili in other pathogenic bacteria have been characterized as playing a major role in attachment to epithelial cells, there are very few studies to suggest that TCP acts as an attachment factor. Taking this into consideration, we investigated the function of TCP in attachment to …

Telemedicine And Advanced Technology Research Center: Quarterly Report, April 18th, 2011 To July 17th, 2011, Bea Babbitt

Telemedicine & Advanced Technology Research Center

Development of a P.O.I. and a Blended Learning Ecology for use in Combat Lifesaver Skills Training for the Army.

Na/K-Atpase Mimetic Pnaktide Peptide Inhibits The Growth Of Human Cancer Cells, Zhichuan Li, Zhongbing Zhang, Joe X. Xie, Xin Li, Jiang Tian, Ting Cai, Hongaun Cui, Hanfei Ding, Joseph I. Shapiro Md, Zijian Xie

Biochemistry and Microbiology

Cells contain a large pool of non-pumping Na/K-ATPase that participates in signal transduction. Here, we show that the expression of α1 Na/K-ATPase is significantly reduced in human prostate carcinoma as well as in several human cancer cell lines. This down-regulation impairs the ability of Na/K-ATPase to regulate Src-related signaling processes. Supplement of pNaKtide, a peptide derived from α1 Na/K-ATPase, reduces activities of Src and Src effectors. Consequently, these treatments stimulate apoptosis and inhibit growth in cultures of human cancer cells. Moreover, administration of pNaKtide inhibits angiogenesis and growth of tumor xenograft. Thus, the new findings demonstrate the in vivo effectiveness …

Microglial P38Α Mapk Is A Key Regulator Of Proinflammatory Cytokine Up-Regulation Induced By Toll-Like Receptor (Tlr) Ligands Or Beta-Amyloid (Aβ), Adam D. Bachstetter, Bin Xing, Lucia De Almeida, Edgardo R. Dimayuga, D. Martin Watterson, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Overproduction of proinflammatory cytokines from activated microglia has been implicated as an important contributor to pathophysiology progression in both acute and chronic neurodegenerative diseases. Therefore, it is critical to elucidate intracellular signaling pathways that are significant contributors to cytokine overproduction in microglia exposed to specific stressors, especially pathways amenable to drug interventions. The serine/threonine protein kinase p38α MAPK is a key enzyme in the parallel and convergent intracellular signaling pathways involved in stressor-induced production of IL-1β and TNFα in peripheral tissues, and is a drug development target for peripheral inflammatory diseases. However, much less is known about the quantitative …

Com Outlook Summer 2011, College Of Osteopathic Medicine

COM Outlook

No abstract provided.

Recruitment And Retention Of Diverse Populations In Antiretroviral Clinical Trials: Practical Applications From The Gender, Race And Clinical Experience Study., Ron Falcon, Dawn Averitt Bridge, Judith Currier, Kathleen Squires, Debbie Hagins, Deborah Schaible, Robert Ryan, Joseph Mrus

Division of Infectious Diseases and Environmental Medicine Faculty Papers

BACKGROUND: Women, particularly women of color, remain underrepresented in antiretroviral (ARV) clinical trials. To evaluate sex-based differences in darunavir/ritonavir-based therapy, the Gender, Race And Clinical Experience (GRACE) study was designed to enroll and retain a high proportion of women representative of the racial/ethnic demographics of women with HIV/AIDS in the United States. The recruitment and retention strategies used in GRACE are described in this article.

METHODS: Recruitment and retention strategies targeting women included selecting study sites that focused on women, involving community consultants, site-specific enrollment plans, access to other ARV drugs, study branding, site and patient toolkits, targeted public relations, …

Comparison Of Chromogenic Urinary Tract Infection Medium With Cysteine Lactose Electrolyte Deficient Media In A Resource Limited Setting, Saba Qaiser, Muhammad Zeeshan, Kausar Jabeen, Tanwir Ahsan, Afia Zafar

Department of Pathology and Laboratory Medicine

OBJECTIVES: To compare the chromogenic UTI medium (CUM) with cysteine lactose electrolyte deficient medium (CLED) in terms of isolation of uropathogens, turnaround time and cost.

METHODS: A total of 251 urine samples were selected and inoculated on both CLED and CUM, growth was observed after 24 and 48 hours of incubation. Isolates were identified by colony's colour and biochemical tests. Turnaround time for identification and cost was calculated till final identification of microorganisms.

RESULTS: A discrepancy in isolation was observed in seven samples with growth on CUM in 24 hours while in 48 hours on CLED. There was 100% agreement …