Digital Commons Network^™

A Novel Engineered Vegf Blocker With An Excellent Pharmacokinetic Profile And Robust Anti-Tumor Activity, L. Liu, H. Yu, X. Huang, H. Tan, S. Li, Y. Luo, L. Zhang, S. Jiang, C. C. Chu, W. Tian, +4 Additional Authors

Journal Articles

BACKGROUND: Relatively poor penetration and retention in tumor tissue has been documented for large molecule drugs including therapeutic antibodies and recombinant immunoglobulin constant region (Fc)-fusion proteins due to their large size, positive charge, and strong target binding affinity. Therefore, when designing a large molecular drug candidate, smaller size, neutral charge, and optimal affinity should be considered. METHODS: We engineered a recombinant protein by molecular engineering the second domain of VEGFR1 and a few flanking residues fused with the Fc fragment of human IgG1, which we named HB-002.1. This recombinant protein was extensively characterized both in vitro and in vivo for …

A-803467, A Tetrodotoxin-Resistant Sodium Channel Blocker, Modulates Abcg2-Mediated Mdr In Vitro And In Vivo, Nagaraju Anreddy, Atish Patel, Yun-Kai Zhang, Yi-Jun Wang, Suneet Shukla, Rishil J. Kathawala, Priyank Kumar

Touro College of Pharmacy (New York) Publications and Research

ATP-binding cassette subfamily G member 2 (ABCG2) is a member of the ABC transporter superfamily proteins, which has been implicated in the development of multidrug resistance (MDR) in cancer, apart from its physiological role to remove toxic substances out of the cells. The diverse range of substrates of ABCG2 includes many antineoplastic agents such as topotecan, doxorubicin and mitoxantrone. ABCG2 expression has been reported to be significantly increased in some solid tumors and hematologic malignancies, correlated to poor clinical outcomes. In addition, ABCG2 expression is a distinguishing feature of cancer stem cells, whereby this membrane transporter facilitates resistance to the …

Γ-Secretase Inhibitor Alleviates Acute Airway Inflammation Of Allergic Asthma In Mice By Downregulating Th17 Cell Differentiation, Weixi Zhang, Xueya Zhang, Anqun Sheng, Cuiye Weng, Tingting Zhu, Wei Zhao, Changchong Li

Pediatrics Publications

T helper 17 (Th17) cells play an important role in the pathogenesis of allergic asthma. Th17 cell differentiation requires Notch signaling. γ-Secretase inhibitor (GSI) blocks Notch signaling; thus, it may be considered as a potential treatment for allergic asthma. The aim of this study was to evaluate the effect of GSI on Th17 cell differentiation in a mouse model of allergic asthma. OVA was used to induce mouse asthma model in the presence and absence of GSI. GSI ameliorated the development of OVA-induced asthma, including suppressing airway inflammation responses and reducing the severity of clinical signs. GSI also significantly …

Notch Receptor Expression In Human Brain Arteriovenous Malformations, S. Hill-Felberg, H. H. Wu, S. A. Toms, A. R. Dehdashti

Journal Articles

The roles of the Notch pathway proteins in normal adult vascular physiology and the pathogenesis of brain arteriovenous malformations are not well-understood. Notch 1 and 4 have been detected in human and mutant mice vascular malformations respectively. Although mutations in the human Notch 3 gene caused a genetic form of vascular stroke and dementia, its role in arteriovenous malformations development has been unknown. In this study, we performed immunohistochemistry screening on tissue microarrays containing eight surgically resected human brain arteriovenous malformations and 10 control surgical epilepsy samples. The tissue microarrays were evaluated for Notch 1-4 expression. We have found that …

Radionuclide Imaging: Past, Present And Future Outlook In The Diagnosis Of Infected Prosthetic Joints, L. Brammen, C. Palestro, H. Sinzinger

Journal Articles

Objective: A serious complication of joint replacement surgery is infection, which results in prolonged invalidity as well as removal and subsequent re-implantation after lengthy antibiotic therapy. In terms of diagnostic imaging, nuclear medicine has presented several tracers and imaging modalities over the years to be used in prosthetic joint infection. The PubMed/MEDLINE literature database was systematically examined for publications on infection, arthroplasty, joint replacement, prosthetic joint, gallium, labeled leukocytes, sulfur colloid, antimicrobial peptides, Fluorine-18-fluorodeoxyglucose (F-18-FDG), positron emission tomography/computed tomography (PET-CT), and single-photon emission (SPET-CT). This was determined to be a comprehensive review, not a meta-analysis of prosthetic joint infection and …

Detection Of Symptomatic Carotid Plaque Using Source Data From Mr And Ct Angiography: A Correlative Study, A. Gupta, H. Baradaran, E. E. Mtui, H. Kamel, A. Pandya, A. Giambrone, C. Iadecola, P. C. Sanelli

Journal Articles

BACKGROUND: Carotid plaque MRI has been a useful method to characterize vulnerable atherosclerotic plaque elements. Recent investigations have suggested that source images from CT angiography (CTA) and MR angiography (MRA) can identify the simple high-risk features of symptom-producing carotid artery plaque. We studied the correlation and relative diagnostic accuracies of CTA and MRA source images in detecting symptomatic carotid artery plaque. METHODS: Subjects were eligible if they had carotid stenosis between 50 and 99% and had MRA and CTA exams performed within 10 days of one another. We measured the soft (non-calcified) plaque and hard (calcified) plaque thickness on CTA …

Evaluating Blood-Brain Barrier Permeability In Delayed Cerebral Infarction After Aneurysmal Subarachnoid Hemorrhage, J. Ivanidze, K. Kesavabhotla, O. N. Kallas, D. Mir, H. Baradaran, A. Gupta, A. Z. Segal, J. Claassen, P. C. Sanelli

Journal Articles

BACKGROUND AND PURPOSE: Patients with SAH are at increased risk of delayed infarction. Early detection and treatment of delayed infarction remain challenging. We assessed blood-brain barrier permeability, measured as permeability surface area product, by using CTP in patients with SAH with delayed infarction. MATERIALS AND METHODS: We performed a retrospective study of patients with SAH with delayed infarction on follow-up NCCT. CTP was performed before the development of delayed infarction. CTP data were postprocessed into permeability surface area product, CBF, and MTT maps. Coregistration was performed to align the infarcted region on the follow-up NCCT with the corresponding location on …

Temporary Mechanical Circulatory Support: A Review Of The Options, Indications, And Outcomes, N. A. Gilotra, G. R. Stevens

Journal Articles

Cardiogenic shock remains a challenging disease entity and is associated with significant morbidity and mortality. Temporary mechanical circulatory support (MCS) can be implemented in an acute setting to stabilize acutely ill patients with cardiomyopathy in a variety of clinical situations. Currently, several options exist for temporary MCS. We review the indications, contraindications, clinical applications, and evidences for a variety of temporary circulatory support options, including the intra-aortic balloon pump (IABP), extracorporeal membrane oxygenation (ECMO), CentriMag blood pump, and percutaneous ventricular assist devices (pVADs), specifically the TandemHeart and Impella.

Planning And Guidance Of Cardiac Resynchronization Therapy-Lead Implantation By Evaluating Coronary Venous Anatomy Assessed With Multidetector Computed Tomography, J. N. Catanzaro, J. N. Makaryus, R. Jadonath, A. N. Makaryus

Journal Articles

OBJECTIVES: We sought to evaluate the utility of multidetector computed tomography (MDCT) in preoperative planning of cardiac resynchronization therapy (CRT) device implantation. BACKGROUND: Variation in coronary venous anatomy can affect optimal lead placement and may warrant preimplantation visualization prior to CRT lead placement. METHODS: Prospective randomized enrollment of 29 patients (17 males; mean age at implant 66.7 +/- 12.8 years) was undertaken. Patients were randomized to preimplantation MDCT (GE((R)) 64-detector Lightspeed, n = 16) or no MDCT. Implantation was planned based on three-dimensional coronary venous reconstruction as visualized in the CT group. Measurement of coronary sinus (CS) angulation, CS ostial …

Obstructive Sleep Apnea As A Risk Factor For Type 2 Diabetes Mellitus, P. Rajan, H. Greenberg

Journal Articles

No abstract provided.

Phase Ii Double-Blind Placebo-Controlled Randomized Study Of Armodafinil For Brain Radiation-Induced Fatigue, B. R. Page, E. G. Shaw, L. Lu, D. Bryant, D. Grisell, G. J. Lesser, D. C. Monitto, M. J. Naughton, S. R. Savona, M. D. Chan, +3 Additional Authors

Journal Articles

BACKGROUND: Common acute-term side effects of brain radiotherapy (RT) include fatigue, drowsiness, decreased physical functioning, and decreased quality of life (QOL). We hypothesized that armodafinil (a wakefulness-promoting drug known to reduce fatigue and increase cognitive function in breast cancer patients receiving chemotherapy) would result in reduced fatigue and sleepiness for patients receiving brain RT. METHODS: A phase II, multi-institutional, placebo-controlled randomized trial assessed feasibility of armodafinil 150 mg/day in participants receiving brain RT, from whom we obtained estimates of variability for fatigue, sleepiness, QOL, cognitive function, and treatment effect. RESULTS: From September 20, 2010, to October 20, 2012, 54 participants …

Biologics In Achilles Tendon Healing And Repair: A Review, E. Shapiro, D. Grande, M. Drakos

Journal Articles

Injuries of the Achilles tendon are relatively common with potentially devastating outcomes. Healing Achilles tendons form a fibrovascular scar resulting in a tendon which may be mechanically weaker than the native tendon. The resulting strength deficit causes a high risk for reinjury and other complications. Treatments using biologics aim to restore the normal properties of the native tendon and reduce the risk of rerupture and maximize tendon function. The purpose of this review was to summarize the current findings of various therapies using biologics in an attempt to improve the prognosis of Achilles tendon ruptures and tendinopathies. A PubMed search …

An Immunohistochemical Analysis Of Stathmin 1 Expression In Uterine Smooth Muscle Tumors: Differential Expression In Leiomyosarcomas And Leiomyomas, M. M. Allen, J. J. Douds, S. X. Liang, M. M. Desouki, V. Parkash, O. Fadare

Journal Articles

The oncogenic phosphatidylinositol 3-kinase-AKT-mammlian target of rapamycin pathway (PI3K-AKT-mTOR) pathway is known to be activated in uterine smooth muscle tumors, and Stathmin 1 (STMN1) expression has been identified as a marker of PI3K-AKT-mTOR pathway activation. We hypothesized that STMN1 may have some diagnostic utility and explored how well STMN1 expression correlated with histologic classifications of uterine smooth muscle tumors into benign and malignant groupings. 84 smooth muscle tumors were assessed for STMN1 expression by immunohistochemistry. These included spindle cell leiomyosarcoma (n=32), conventional spindle cell leiomyomas (n=30), atypical (symplastic) leiomyoma (n=5), cellular leiomyoma (n=7), smooth muscle tumor of uncertain malignant potential …

Liver X Receptor-Dependent Inhibition Of Microglial Nitric Oxide Synthase 2, Julie R Secor Mcvoy, Hanadi Ajam Oughli, Unsong Oh

Neurology Publications

Background

The nuclear receptor liver X receptor (LXR) exerts transcriptional control over lipid metabolism and inflammatory response in cells of the myeloid lineage, suggesting that LXR may be a potential target in a number of chronic neuroinflammatory and neurodegenerative diseases where persistent microglial activation has been implicated in the pathogenesis.

Methods

The effect of LXR activation on microglia and central nervous system (CNS) inflammation was studied using a synthetic LXR agonist in cultured microglia, a microglial cell line and experimental allergic encephalomyelitis (EAE), an animal model of CNS inflammation.

Results

LXR activation inhibited nitric oxide synthase 2, inducible (Nos2 …

Ua94/6/15 Student / Alumni Personal Papers Wku Dorris Hutchinson, Wku Archives

WKU Archives Collection Inventories

Correspondence and publications created by and about the Dorris Hutchison during her time at Sloan-Kettering Institute.

Progressive Cognitive Deficit, Motor Impairment And Striatal Pathology In A Transgenic Huntington Disease Monkey Model From Infancy To Adulthood, Anthony W. S. Chan, Jie Jiang, Yiju Chen, Chunxia Li, Melinda S. Prucha, Yijuan Hu, Tim Chi, Sean Moran, Tayeb Rahim, Shihua Li, Xiaojiang Li, Stuart M. Zola, Claudia M. Testa, Hui Mao, Rosa Villalba, Yoland Smith, Xiaodong Zhang, Jocelyne Bachevalier

Neurology Publications

One of the roadblocks to developing effective therapeutics for Huntington disease (HD) is the lack of animal models that develop progressive clinical traits comparable to those seen in patients. Here we report a longitudinal study that encompasses cognitive and motor assessment, and neuroimaging of a group of transgenic HD and control monkeys from infancy to adulthood. Along with progressive cognitive and motor impairment, neuroimaging revealed a progressive reduction in striatal volume. Magnetic resonance spectroscopy at 48 months of age revealed a decrease of N-acetylaspartate (NAA), further suggesting neuronal damage/loss in the striatum. Postmortem neuropathological analyses revealed significant neuronal loss in …

Spag17 Deficiency Results In Skeletal Malformations And Bone Abnormalities, Maria Eugenia Teves, Gobalakrishnan Sundaresan, David J. Cohen, Sharon L. Hyzy, Illya Kajan, Melissa Maczis, Zhibing Zhang, Richard M. Costanzo, Jamal Zweit, Zvi Schwartz, Barbara` D. Boyan, Jerome F. Strauss Iii

Obstetrics and Gynecology Publications

Height is the result of many growth and development processes. Most of the genes associated with height are known to play a role in skeletal development. Single-nucleotide polymorphisms in the SPAG17 gene have been associated with human height. However, it is not clear how this gene influences linear growth. Here we show that a targeted mutation in Spag17 leads to skeletal malformations. Hind limb length in mutants was significantly shorter than in wild-type mice. Studies revealed differences in maturation of femur and tibia suggesting alterations in limb patterning. Morphometric studies showed increased bone formation evidenced by increased trabecular bone area …

Sperm Associated Antigen 6 (Spag6) Regulates Fibroblast Cell Growth, Morphology, Migration And Ciliogenesis, Wei Li, Abir Mukherjee, Jinhua Wu, Ling Zhang, Maria E. Teves, Hongfei Li, Shanti Nambiar, Scott C. Henderson, Alan R. Horwitz, Jerome F. Strauss Iii, Xianjun Fang, Zhibing Zhang

Obstetrics and Gynecology Publications

Mammalian Spag6 is the orthologue of Chlamydomonas PF16, which encodes a protein localized in the axoneme central apparatus, and regulates flagella/cilia motility. Most Spag6-deficient mice are smaller in size than their littermates. Because SPAG6 decorates microtubules, we hypothesized that SPAG6 has other roles related to microtubule function besides regulating flagellar/cilia motility. Mouse embryonic fibroblasts (MEFs) were isolated from Spag6-deficient and wild-type embryos for these studies. Both primary and immortalizedSpag6-deficient MEFs proliferated at a much slower rate than the wild-type MEFs, and they had a larger surface area. Re-expression of SPAG6 in the Spag6-deficient MEFs …

A Dietary Intervention For Chronic Diabetic Neuropathy Pain: A Randomized Controlled Pilot Study, A. E. Bunner, C. L. Wells, J. Gonzales, U. Agarwal, Elham Bayat, Neal D. Barnard

Neurology Faculty Publications

Background:

Diabetic neuropathy is a common and often debilitating condition for which available treatments are limited. Because a low-fat plant-based diet has been shown to improve glycemic control in individuals with type 2 diabetes, we hypothesized that such a diet would reduce painful symptoms of diabetic neuropathy.

Methods:

In this 20-week pilot study, individuals with type 2 diabetes and painful diabetic neuropathy were randomly assigned to two groups. The intervention group was asked to follow a low-fat, plant-based diet, with weekly classes for support in following the prescribed diet, and to take a vitamin B12 supplement. The control group was …

Characterizing The Propagation Of Uterine Electrophysiological Signals Recorded With A Multi-Sensor Abdominal Array In Term Pregnancies., Diana Escalona-Vargas, Rathinaswamy B. Govindan, Adrian Furdea, Pam Murphy, Curtis L Lowery, Hari Eswaran

Pediatrics Faculty Publications

The objective of this study was to quantify the number of segments that have contractile activity and determine the propagation speed from uterine electrophysiological signals recorded over the abdomen. The uterine magnetomyographic (MMG) signals were recorded with a 151 channel SARA (SQUID Array for Reproductive Assessment) system from 36 pregnant women between 37 and 40 weeks of gestational age. The MMG signals were scored and segments were classified based on presence of uterine contractile burst activity. The sensor space was then split into four quadrants and in each quadrant signal strength at each sample was calculated using center-of-gravity (COG). To …

The Effect Of Statins On Blood Gene Expression In Copd, Ma'en Obeidat, Nick Fishbane, Yunlong Nie, Virginia Chen, Zsuzsanna Hollander, Scottj Tebbutt, Yohan Bossé, Raymond T. Ng, Bruce E. Miller, Bruce Mcmanus, Stephen I. Rennard, Peter D. Paré, Don D. Sin

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: COPD is currently the fourth leading cause of death worldwide. Statins are lipid lowering agents with documented cardiovascular benefits. Observational studies have shown that statins may have a beneficial role in COPD. The impact of statins on blood gene expression from COPD patients is largely unknown.

OBJECTIVE: Identify blood gene signature associated with statin use in COPD patients, and the pathways underpinning this signature that could explain any potential benefits in COPD.

METHODS: Whole blood gene expression was measured on 168 statin users and 451 non-users from the ECLIPSE study using the Affymetrix Human Gene 1.1 ST microarray chips. …

A Mobile Image Enhancement Technology For Visually Impaired, Fahao Qiao

Dissertations, Master's Theses and Master's Reports - Open

In this thesis, an image enhancement application is developed for low-vision patients when they use iPhones to see images/watch videos. The thesis has two contributions. The first contribution is the new image enhancement algorithm which combines human vision features. The new image enhancement algorithm is modified from a wavelet transform based image enhancement algorithm developed by Dr. Jinshan Tang. Different from the original algorithm, the new image enhancement algorithm combines human visual feature into the algorithm and thus can make the new algorithm more effective. Experimental simulation results show that the proposed algorithm has better visual results than the algorithm …

Early Initiation Of Antiretroviral Therapy Can Functionally Control Productive Hiv-1 Infection In Humanized-Blt Mice, Qingsheng Li, For Yue Tso, Guobin Kang, Wuxun Lu, Yue Li, Wenjin Fan, Zhe Yuan, Christopher J. Destache, Charles Wood

Nebraska Center for Virology: Faculty Publications

Background—Recent reports showed that functional control of HIV-1 infection for a prolonged time is possible by early anti-retroviral therapy (ART); however its underlying mechanism needs to be studied with a suitable animal model. Recently, humanized-BLT (bone marrow, liver and thymus) mouse (hu-BLT) was shown to be an excellent model for studying HIV-1 infection. We thus tested the feasibility of studying functional control of HIV-1 infection using hu-BLT mice.

Methods—Animals in three treatment groups (Rx-6h, Rx-24h, Rx-48h) and untreated group were infected with HIV-1, followed by ART initiation at 6, 24 or 48 hours post-infection and continued daily for two weeks. …

The Role Of Dendritic Cell Subsets And Innate Immunity In The Pathogenesis Of Type 1 Diabetes And Other Autoimmune Diseases, Jeffrey D. Price, Kristin V. Tarbell

Nebraska Center for Virology: Faculty Publications

Dendritic cells (DCs) are key antigen-presenting cells that have an important role in autoimmune pathogenesis. DCs control both steady-state T cell tolerance and activation of pathogenic responses. The balance between these two outcomes depends on several factors, including genetic susceptibility, environmental signals that stimulate varied innate responses, and which DC subset is presenting antigen. Although the specific DC phenotype can diverge depending on the tissue location and context, there are four main subsets identified in both mouse and human: conventional cDC1 and cDC2, plasmacytoid DCs, and monocyte-derived DCs. In this review, we will discuss the role of these subsets in …

The Experiences Of Black American Older Adults Managing Pain: A Nursing Ethnography, Sheria Grice Robinson

Wayne State University Dissertations

Introduction: Pain can negatively affect quality of life for Black elders. They are less likely to report pain concerns and have voiced pain needs adequately met. To better understand the pain management experiences and concerns of Black elders, an ethnographic study was completed within an urban, low-income, elder housing facility. Methods: 106 participants completed a questionnaire comprised of a demographic tool, the PROMIS Global Health Scale (PROMIS), the Brief Pain Inventory (BPI), and the Psychological Stress Measure (PSM-9). Additionally, participant observation, informal interviews, and 20 formal recorded interviews with individuals identified as having pain were completed. Qualitative and frequency analysis …

Genetic Modifiers Of Duchenne Muscular Dystrophy And Dilated Cardiomyopathy., Andrea Barp, Luca Bello, Luisa Politano, Paola Melacini, Chiara Calore, Eric P. Hoffman, +16 Additional Authors

Genomics and Precision Medicine Faculty Publications

OBJECTIVE: Dilated cardiomyopathy (DCM) is a major complication and leading cause of death in Duchenne muscular dystrophy (DMD). DCM onset is variable, suggesting modifier effects of genetic or environmental factors. We aimed to determine if polymorphisms previously associated with age at loss of independent ambulation (LoA) in DMD (rs28357094 in the SPP1 promoter, rs10880 and the VTTT/IAAM haplotype in LTBP4) also modify DCM onset.

METHODS: A multicentric cohort of 178 DMD patients was genotyped by TaqMan assays. We performed a time-to-event analysis of DCM onset, with age as time variable, and finding of left ventricular ejection fraction < 50% and/or end diastolic volume > 70 mL/m2 as …

Nitric Oxide Generating/Releasing Materials, Honying Liang, Parimala Nacharaju, Adam J. Friedman, Joel Friedman

Dermatology Faculty Publications

Harnessing the impressive therapeutic potential of nitric oxide (NO) remains an ongoing challenge. This paper describes several of the current strategies both with respect to the underlying chemistry and physics and to the applications where they have shown promise. Included in this overview are molecular systems such as NONOates that release NO through chemical reactions and delivery vehicles such as nanoparticles that can generate, store, transport and deliver NO and related bioactive forms of NO such as nitrosothiols. Although there has been much positive movement, it is clear that we are only at the early stages of knowing how to …

Complications And Predictors Of Need For Return To The Operating Room In The Treatment Of Supracondylar Humerus Fractures In Children, Matthew E. Oetgen, Gudrun E. Mirick, Lara Atwater, John F. Lovejoy

Orthopaedic Surgery Faculty Publications

Supracondylar humerus fractures are common pediatric injuries. Little is known about the risk factors for repeat operative procedures. A retrospective chart review of 709 patients treated for a displaced supracondylar humerus fracture was performed to identify risk factors for return to the operating room during the initial post-operative period. Deviations of routine fracture care were recorded and complication rates were compared between Gartland type 2 and 3 fractures using logistic regression. Type 3 fractures were found to have a higher complication rate, and, specifically, more peri-operative nerve palsies, more likely to need to return to the operating room for hardware …

Impact Of Prenatal Environmental Stress On Cortical Development, Seiji Ishii, Kazue Hashimoto-Torii

Pediatrics Faculty Publications

Prenatal exposure of the developing brain to various types of environmental stress increases susceptibility to neuropsychiatric disorders such as autism, attention deficit hyperactivity disorder and schizophrenia. Given that even subtle perturbations by prenatal environmental stress in the cerebral cortex impair the cognitive and memory functions, this review focuses on underlying molecular mechanisms of pathological cortical development. We especially highlight recent works that utilized animal exposure models, human specimens or/and induced Pluripotent Stem (iPS) cells to demonstrate: 1. molecular mechanisms shared by various types of environmental stressors, 2. the mechanisms by which the affected extracortical tissues indirectly impact the cortical development …

Mosquito-Borne Diseases In Mississippi, Ryan J. Rodriguez

Department of Entomology: Distance Master of Science Projects

Life Cycle:
Egg Must be exposed to water to hatch
Larvae Live in aquatic habitats
Pupa Stay near the surface of water to breath
Adults: Only females feed on blood; Males feed on nectar

Public Health •Besides being a nuisance, they cause numerous health hazards to humans (and other animals) •In some cases, they may cause severe allergic reactions •Diseases they transmit: •Eastern Equine Encephalitis •Japanese Encephalitis •La Crosse Encephalitis •St. Louis Encephalitis •West Nile Virus •Western Equine Encephalitis •Dengue Fever •Malaria •Rift Valley Fever •Yellow Fever

Mosquito-Borne Diseases in Mississippi and its Vectors •Chikungunya Virus •Aedes species •Eastern Equine …