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Characterization Of The Anti-Angiogenic Properties Of Kdr-Ig4-7 And Its Variants As Potential Anti-Cancer Therapeutics, Jang Pyo Park

All Dissertations

Beginning with the development of an embryo and throughout one's adult life angiogenesis plays an essential role for organ growth and repair. The balancing of pro-angiogenic factors to anti-angiogenic factors is what regulates the process of angiogenesis. When this balance is disrupted in one direction or the other, numerous disorders can occur including ocular and inflammatory diseases and, in particular, tumor growth and metastasis. Therefore, inhibition of angiogenesis has become an effective therapy for arresting the growth of tumors.
A key regulator of angiogenesis involves vascular endothelial growth factor (VEGF) and its receptor, VEGFR-2 (KDR). The binding of VEGF to …

Evaluation Of Human Prolactin, Its Antagonist, And Antagonist-Based Fusion Proteins As Chemopreventative And Therapeutic Agents, Seth Tomblyn

All Dissertations

Cancer is a collection of diseases with many different manifestations and is the second leading cause of death in the United States. Breast cancer accounts for nearly one third of cancer diagnosis in women. Prolactin (PRL) functions as a lactogen and as a mammary gland differentiation factor. PRL acts in an autocrine/paracrine manner within the mammary gland and in breast tumors which implies PRL may be involved in breast cancer progression. This is corroborated by the PRLR over-expression in breast cancer cells lines and the majority of patient biopsies. These reasons make PRL and PRLR attractive targets for breast cancer …

Fluorosis: A Rare Cause Of Spinal Cordcompression, Maimoona Siddiqui, Azra Zafar, M. Salman, Yaseen Pathan

Pakistan Journal of Neurological Sciences (PJNS)

No abstract provided.

Neurology, Ayeesha K. Kamal

Pakistan Journal of Neurological Sciences (PJNS)

No abstract provided.

How To Prevent Perioperative Myocardial Injury: The Conundrum Continues, Jian-Zhong Sun, David Maguire

Department of Anesthesiology Faculty Papers

BACKGROUND: Perioperative myocardial injury (PMI) remains a major cause of perioperative morbidity and mortality but clinical strategies to prevent PMI are still uncertain.

METHODS AND RESULTS: We comprehensively searched PubMed for major research articles concerning clinical strategies to prevent PMI. The key findings are as follows: (1) the American College of Cardiology/American Heart Association guideline update for perioperative cardiovascular evaluation for noncardiac surgery is very useful to stratify cardiac risk preoperatively; (2) cardiac troponin has emerged as a biomarker to diagnose postoperative PMI and to predict clinical outcomes; (3) coronary revascularization before noncardiac surgery probably would provide cardiac protection in …

Targeted Therapies In The Management Of Metastatic Bladder Cancer., Matteo Fassan, Edouard J. Trabulsi, Leonard G Gomella, Raffaele Baffa

Department of Urology Faculty Papers

The management of metastatic urothelial carcinoma (UC) of the bladder is a common and complex clinical challenge. Despite the fact that UC is one of the most frequent tumors in the population, long term survival for metastatic disease remains low, and chemotherapy is curative for only a small minority of patients. UC is genetically heterogeneous, and it is surrounded by a complex tissue microenvironment. The problems of clinical practice in the field of metastatic bladder cancer have begun to stimulate translational research. Advances in the understanding of the molecular biology of urothelial cancer continue to contribute to the identification of …

Modulation Of Tgf-Beta Signaling By Proinflammatory Cytokines In Articular Chondrocytes., Jorge A. Roman-Blas, David G. Stokes, Sergio A. Jimenez

Department of Medicine Faculty Papers

OBJECTIVE: The normal structure and function of articular cartilage are the result of a precisely balanced interaction between anabolic and catabolic processes. The transforming growth factor-beta (TGF-beta) family of growth factors generally exerts an anabolic or repair response; in contrast, proinflammatory cytokines such as interleukin 1 beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) exert a strong catabolic effect. Recent evidence has shown that IL-1beta, and TNF-alpha, and the TGF-beta signaling pathways share an antagonistic relationship. The aim of this study was to determine whether the modulation of the response of articular chondrocytes to TGF-beta by IL-1beta or TNF-alpha signaling pathways …

Neuroradiology, Zafar Sajjad

Pakistan Journal of Neurological Sciences (PJNS)

No abstract provided.

Psychiatry, Syed Ahmer

Pakistan Journal of Neurological Sciences (PJNS)

No abstract provided.

Cardiopulmonary Predicators Of Dysfunctional Ventilator Weaning Response After Coronary Artery Bypass Graft, Annapoorna Mary

Theses and Dissertations (ETD)

Although the majority of coronary artery bypass graft (CABG) surgery patients are extubated within 6 to 8 hours following surgery, 20% to 40% of patients remain intubated 12 hours after surgery due to dysfunctional ventilator weaning response (DVWR). DVWR associated with increased morbidity and mortality (30% to 43%) following CABG surgery. Finding significant antecedence to predict DVWR could help to identify and prevent the complications from DVWR after CABG surgery. Literature review revealed that there is an association between cardiopulmonary indicators (CPI) and DVWR after CABG surgery. Cardiopulmonary indicators are the selected hemodynamic parameters that have an association with DVWR. …

Outcome Of Triple Procedure In Older Children With Developmental Dysplasia Of Hip (Ddh), Masood Umer, Haq Nawaz, Pashtoon Murtaza Kasi, Mahmood Ahmed

Department of Surgery Docs

Objective: To evaluate the radiographic and functional results of the triple procedure (open reduction, femoral shortening and Salter's Osteotomy) in the treatment of Developmental Dysplasia of the Hip (DDH) disease in older children. Methods: This case-series comprising 23 patients (29 hips) underwent the triple procedure of open reduction, femoral shortening and Salter osteotomy, at Aga Khan University Hospital between June 1995 and June 2005. Patients were classified pre-operatively according to the Tonnis class. Postoperative functional evaluation was performed using Modified MacKay's scoring system and radiographic assessment using Severin's scoring method. Results: The mean age of patients at presentation was 6.84 …

Laryngeal Mask Airway Insertion Anaesthesia And Insertion Techniques, Abdul Monem, Fauzia A. Khan

Department of Anaesthesia

Laryngeal Mask Airway has gained wide acceptance for routine airway management, difficult airway and in emergency situations. The classical method of insertion was recommended by Dr Brain. Over the years various induction and insertion techniques have been described with variable results. Combination of induction agents with narcotics, with or without small dose muscle relaxants has been found to be very effective. There is less also lesser incidence of mucosal trauma with partially inflated cuff. Insertion with cuff facing laterally or backwards and rotating it forwards into position has also been described. A review of various options and their advantages and …

Bullet-Induced Synovitis As A Cause Of Secondary Osteoarthritis Of The Hip Joint: A Case Report And Review Of Literature, A Rehman, Masood Umer, Yasir J Sepah, Muhammad A Wajid

Department of Surgery Docs

Abstract

BACKGROUND:

With increasing prevalence of gunshot injuries we are seeing more patients with retained bullet fragments lodged in their bodies. Embedded lead bullets are usually considered inert after their kinetic energy has dissipated hence these are not removed routinely. However, exposure of any foreign body to synovial fluid may lead to rapid degradation and hence result in systemic absorption, causing local and systemic symptoms. We present the case of a thirty year old man who came to our out patient department with a history of progressive, severe hip pain ten years after a gun shot injury to his right …

Neurogranin Controls The Spatiotemporal Pattern Of Postsynaptic Ca2+/Cam Signaling, Yoshihisa Kubota, John A Putkey, M Neal Waxham

Faculty, Staff and Student Publications

Neurogranin (Ng) is a postsynaptic IQ-motif containing protein that accelerates Ca(2+) dissociation from calmodulin (CaM), a key regulator of long-term potentiation and long-term depression in CA1 pyramidal neurons. The exact physiological role of Ng, however, remains controversial. Two genetic knockout studies of Ng showed opposite outcomes in terms of the induction of synaptic plasticity. To understand its function, we test the hypothesis that Ng could regulate the spatial range of action of Ca(2+)/CaM based on its ability to accelerate the dissociation of Ca(2+) from CaM. Using a mathematical model constructed on the known biochemistry of Ng, we calculate the cycle …

Wingless Activity In The Precursor Cells Specifies Neuronal Migratory Behavior In The Drosophila Nerve Cord, Krishna Moorthi Bhat

Faculty, Staff and Student Publications

Neurons and their precursor cells are formed in different regions within the developing CNS, but they migrate and occupy very specific sites in the mature CNS. The ultimate position of neurons is crucial for establishing proper synaptic connectivity in the brain. In Drosophila, despite its extensive use as a model system to study neurogenesis, we know almost nothing about neuronal migration or its regulation. In this paper, I show that one of the most studied neuronal pairs in the Drosophila nerve cord, RP2/sib, has a complicated migratory route. Based on my studies on Wingless (Wg) signaling, I report that the …

Human Tob, An Antiproliferative Transcription Factor, Is A Poly(A)-Binding Protein-Dependent Positive Regulator Of Cytoplasmic Mrna Deadenylation, Nader Ezzeddine, Tsung-Cheng Chang, Wenmiao Zhu, Akio Yamashita, Chyi-Ying A Chen, Zhenping Zhong, Yukiko Yamashita, Dinghai Zheng, Ann-Bin Shyu

Faculty, Staff and Student Publications

In mammalian cells, mRNA decay begins with deadenylation, which involves two consecutive phases mediated by the PAN2-PAN3 and the CCR4-CAF1 complexes, respectively. The regulation of the critical deadenylation step and its relationship with RNA-processing bodies (P-bodies), which are thought to be a site where poly(A)-shortened mRNAs get degraded, are poorly understood. Using the Tet-Off transcriptional pulsing approach to investigate mRNA decay in mouse NIH 3T3 fibroblasts, we found that TOB, an antiproliferative transcription factor, enhances mRNA deadenylation in vivo. Results from glutathione S-transferase pull-down and coimmunoprecipitation experiments indicate that TOB can simultaneously interact with the poly(A) nuclease complex CCR4-CAF1 and …

Oncolog, Volume 52, Number 11, November 2007, Diane Witter, Karen Stuyck, Garth Powis Dphil

OncoLog MD Anderson's Report to Physicians (All issues) Archives

• Outsmarting Brain Cancer
• Protecting the Heart
• House Call: Recognize the Signs of Ovarian Cancer
• DiaLog: Advancing Drug Design in Academia, by Garth Powis, DPhil, Director, Center for Targeted Therapy, Chair, Department of Experimental Therapeutics

Relative Contributions Of Enterococcus Faecalis Og1rf Sortase-Encoding Genes, Srta And Bps (Srtc), To Biofilm Formation And A Murine Model Of Urinary Tract Infection, Kelvin D Kemp, Kavindra V Singh, Sreedhar R Nallapareddy, Barbara E Murray

Faculty, Staff and Student Publications

Deletion mutants of the two sortase genes of Enterococcus faecalis OG1RF were constructed. srtC (renamed here bps for biofilm and pilus-associated sortase) was previously shown to be necessary for the production of Ebp pili and important for biofilm formation and endocarditis. Here, we report that a srtA deletion mutant showed a small (5%) yet significant (P = 0.037) reduction in biofilm relative to OG1RF, while a DeltasrtA Deltabps double mutant showed a much greater reduction (74% versus OG1RF and 44% versus the Deltabps mutant). In a murine urinary tract infection (UTI), the 50% infective doses of both the DeltasrtA Deltabps …

Lung-Derived Macrophage Migration Inhibitory Factor In Adult Patients With Septic Shock, And Its Role In Cardiocirculatory Depression, Hans Lee, Kaie Ojamaa, Greg Ruskin, Erfan Hussain, Maowen Hu, Xinchun Lin, Christine Metz, Yousef Al-Abed, Edmund Mille

Department of Medicine

Migration inhibitory factor (MIF), a critical proinflammatory mediator in sepsis, has a profound affect on cardiovascular function. Our animal studies show that the lungs release MIF into the systemic circulation during late sepsis. MIF released in this way has direct and immediate access to cardiac cells. The purpose of our study was to assess the lung as a source of MIF in human septic shock patients and to further study the MIF-associated pathways involved in cardiovascular depression.

The Resurgence Of The Adora2b Receptor As An Immunotherapeutic Target In Pancreatic Cancer, Inah Lee, James J Knierim

Faculty, Staff and Student Publications

Subfields of the hippocampus display differential dynamics in processing a spatial environment, especially when changes are introduced to the environment. Specifically, when familiar cues in the environment are spatially rearranged, place cells in the CA3 subfield tend to rotate with a particular set of cues (e.g., proximal cues), maintaining a coherent spatial representation. Place cells in CA1, in contrast, display discordant behaviors (e.g., rotating with different sets of cues or remapping) in the same condition. In addition, on average, CA3 place cells shift their firing locations (measured by the center of mass, or COM) backward over time when the animal …

The Effectiveness Of Prophylactic Eye Drops On The Reversal Of Uv-Light Induced Cataracts, Contessa Bly Bowman

Theses and Dissertations

Cataracts are a cloudiness of the lens within the eye which obstructs vision. They are found in many species including rats, dogs, and humans. Vision is hindered where this "cloudiness", made of water build up and broken crystalline, proteins take form. Oculvet is an eye medication, used by veterinarians, containing carnosine as its active ingredient. Topical application of carnosine is reported to be an effective treatment for the prevention and removal of pre-existing cataracts. For this experiment, Sprague- Dawley rats were anesthetized and exposed to ultraviolet radiation, UVB and UVC. They were divided into four groups (n = 32), three …

Computational Identification And Functional Validation Of Regulatory Motifs In Cartilage-Expressed Genes, Sherri R Davies, Li-Wei Chang, Debabrata Patra, Xiaoyun Xing, Karen Posey, Jacqueline Hecht, Gary D Stormo, Linda J Sandell

Faculty, Staff and Student Publications

Chondrocyte gene regulation is important for the generation and maintenance of cartilage tissues. Several regulatory factors have been identified that play a role in chondrogenesis, including the positive transacting factors of the SOX family such as SOX9, SOX5, and SOX6, as well as negative transacting factors such as C/EBP and delta EF1. However, a complete understanding of the intricate regulatory network that governs the tissue-specific expression of cartilage genes is not yet available. We have taken a computational approach to identify cis-regulatory, transcription factor (TF) binding motifs in a set of cartilage characteristic genes to better define the transcriptional regulatory …

A Group M Consensus Envelope Glycoprotein Induces Antibodies That Neutralize Subsets Of Subtype B And C Hiv-1 Primary Viruses, Hua-Xin Liao, Laura L. Sutherland, Shi-Mao Xia, Mary E. Brock, Richard M. Scearce, Stacie Vanleeuwen, S. Munir Alam, Mildred Mcadams, Eric A. Weaver, Zenaido T. Camacho, Ben-Jiang Ma, Yingying Li, Julie M. Decker, Gary J. Nabel, David C. Montefiori, Beatrice H. Hahn, Bette T. Korber, Feng Gao, Barton F. Haynes

Nebraska Center for Virology: Faculty Publications

HIV-1 subtype C is the most common HIV-1 group M subtype in Africa and many parts of Asia. However, to date HIV-1 vaccine candidate immunogens have not induced potent and broadly neutralizing antibodies against subtype C primary isolates. We have used a centralized gene strategy to address HIV-1 diversity, and generated a group M consensus envelope gene with shortened consensus variable loops (CON-S) for comparative studies with wildtype (WT) Env immunogens. Our results indicate that the consensus HIV-1 group M CON-S Env elicited cross-subtype neutralizing antibodies of similar or greater breadth and titer than the WT Envs tested, indicating the …

Western Diet, But Not High Fat Diet, Causes Derangements Of Fatty Acid Metabolism And Contractile Dysfunction In The Heart Of Wistar Rats, Christopher R Wilson, Mai K Tran, Katrina L Salazar, Martin E Young, Heinrich Taegtmeyer

Faculty, Staff and Student Publications

Obesity and diabetes are associated with increased fatty acid availability in excess of muscle fatty acid oxidation capacity. This mismatch is implicated in the pathogenesis of cardiac contractile dysfunction and also in the development of skeletal-muscle insulin resistance. We tested the hypothesis that 'Western' and high fat diets differentially cause maladaptation of cardiac- and skeletal-muscle fatty acid oxidation, resulting in cardiac contractile dysfunction. Wistar rats were fed on low fat, 'Western' or high fat (10, 45 or 60% calories from fat respectively) diet for acute (1 day to 1 week), short (4-8 weeks), intermediate (16-24 weeks) or long (32-48 weeks) …

14-3-3 Proteins Interact With The Beta-Thymosin Repeat Protein Csp24, Terry Crow, Juan-Juan Xue-Bian, Joseph T Neary

Faculty, Staff and Student Publications

Conditioned stimulus pathway protein 24 (Csp24) is a beta-thymosin-like protein that is homologous to other members of the family of beta-thymosin repeat proteins that contain multiple actin binding domains. Actin co-precipitates with Csp24 and co-localizes with it in the cytosol of type-B photoreceptor cell bodies. Several signal transduction pathways have been shown to regulate the phosphorylation of Csp24 and contribute to cellular plasticity. Here, we report the identification of the adapter protein 14-3-3 in lysates of the Hermissenda circumesophageal nervous system and its interaction with Csp24. Immunoprecipitation experiments using an antibody that is broadly reactive with several isoforms of the …

Phosphorylation-Induced Conformational Switching Of Cpi-17 Produces A Potent Myosin Phosphatase Inhibitor, Masumi Eto, Toshio Kitazawa, Fumiko Matsuzawa, Sei-Ichi Aikawa, Jason A. Kirkbride, Noriyoshi Isozumi, Yumi Nishimura, David L. Brautigan, Shin-Ya Ohki

Department of Molecular Physiology and Biophysics Faculty Papers

Phosphorylation of endogenous inhibitor proteins specific for type-1 Ser/Thr phosphatase (PP1) provides a mechanism for reciprocal coordination of kinase and phosphatase activities. Phosphorylation of Thr38 in the inhibitor protein CPI-17 transduces G-protein-mediated signaling into a > 1000-fold increase of inhibitory potency toward myosin phosphatase. We show here the solution NMR structure of phospho-T38-CPI-17 with r. m. s. d. of 0.36 ± 0.06 Å for the backbone secondary structure, which reveals how phosphorylation triggers a conformational change and exposes the PP1 inhibitory surface. This active conformation is stabilized by the formation of a hydrophobic core of intercalated side-chains, which is not formed …

A Serratia Marcescens Oxyr Homolog Mediates Surface Attachment And Biofilm Formation, Robert M. Q. Shanks, Nicholas A. Stella, Eric J. Kalivoda, Megan R. Doe

Dartmouth Scholarship

OxyR is a conserved bacterial transcription factor with a regulatory role in oxidative stress response. From a genetic screen for genes that modulate biofilm formation in the opportunistic pathogen Serratia marcescens, mutations in an oxyR homolog and predicted fimbria structural genes were identified. S. marcescens oxyR mutants were severely impaired in biofilm formation, in contrast to the hyperbiofilm phenotype exhibited by oxyR mutants of Escherichia coli and Burkholderia pseudomallei. Further analysis revealed that OxyR plays a role in the primary attachment of cells to a surface. Similar to what is observed in other bacterial species, S. marcescens OxyR …

Idiopathic Epilepsy Of Childhood And Potassium Ion Channels, Alper I. Dai, Mohammad Wasay

Department of Medicine

Potassium can affect the development of common seizure type and can be defined seizure susceptibility allele. The existence of inward-rectifying potassium (Kir) channels was first recognized half a century ago. The biophysical fingerprint of Kir channels is inward rectification in the current-voltage relationship , which limits potassium efflux at depolarizing membrane potentials. Kir channels are essential in the control of resting membrane potential, coupling of the metabolic cellular state with membrane excitability, and maintenance of potassium homeostasis. The critical interval contains several candidate genes, one of which, KCNJ10, exhibits a potentially important polymorphism with regard to fundamental aspects of seizure …

Pp2cdelta (Ppm1d, Wip1), An Endogenous Inhibitor Of P38 Mapk, Is Regulated Along With Trp53 And Cdkn2a Following P38 Mapk Inhibition During Mouse Preimplantation Development., Jenny A Hickson, Barry Fong, Patricia H Watson, Andrew J Watson

Obstetrics & Gynaecology Publications

Preimplantation embryos utilize mitogen-activated protein kinase signaling (MAPK) pathways to relay signals from the external environment to prepare appropriate responses and adaptations to a changing milieu. It is therefore important to investigate how MAPK pathways are regulated during preimplantation development. This study was conducted to investigate whether PP2Cdelta (Ppm1d, WIP1) is expressed during mouse preimplantation development and to determine the influences of p38 MAPK inhibition on expression of Trp53 (p53), Ppm1d, (WIP1), and Cdkn2a (p16) during mouse preimplantation development. Our results indicate that Trp53, Ppm1d, and Cdkn2a mRNAs and TRP53 and PP2Cdelta proteins are expressed throughout mouse preimplantation development. Treatment …

Re: Various Irrigation Fluids Affect Postoperative Brain Edema And Cellular Damage During Experimental Neurosurgery In Rats, Syed Faraz Kazim, Ather Enam

Section of Neurosurgery

No abstract provided.