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Formulating Effective And Accessible Population-Based Colorectal Cancer Screening Programs, Danielle Luffman Dec 2014

Formulating Effective And Accessible Population-Based Colorectal Cancer Screening Programs, Danielle Luffman

Independent Study Project (ISP) Collection

Colorectal cancer, a type of carcinoma originating in cells of the colon or rectum, continues to rank as the third most prevalent cancer worldwide with 1.36 million cases and the fourth most fatal with 693,881 deaths during 2012. In an attempt to alleviate the burden of colorectal cancer throughout society, governments and non-governmental organizations continue to implement population-based cancer screening programs. These programs, typically designed by a federal authority, offer free screening tests to a given population for a certain type of cancer on a routine basis. National systematic screening programs have effectively reduced the incidence of and mortality from …


Hyperthermia, Radiation And Chemotherapy: The Role Of Heat In Multidisciplinary Cancer Care., Mark Hurwitz, Md, Paul R. Stauffer Dec 2014

Hyperthermia, Radiation And Chemotherapy: The Role Of Heat In Multidisciplinary Cancer Care., Mark Hurwitz, Md, Paul R. Stauffer

Department of Radiation Oncology Faculty Papers

The compelling biologic basis for combining hyperthermia with modern cancer therapies including radiation and chemotherapy was first appreciated nearly half a century ago. Hyperthermia complements radiation as conditions contributing to radio-resistance generally enhance sensitivity to heat and sensitizing effects occur through increased perfusion/tumor oxygenation and alteration of cellular death pathways. Chemosensitization with hyperthermia is dependent on the particular mechanism of effect for each agent with synergistic effects noted for several commonly used agents. Clinically, randomized trials have demonstrated benefit including survival with the addition of hyperthermia to radiation or chemotherapy in treatment of a wide range of malignancies. Improvements in …


Treatment Updates Regarding Anaplastic Oligodendroglioma And Anaplastic Oligoastrocytoma, Khurshid Ahmed Khan, Ahmed Nadeem Abbasi, Nasir Ali Dec 2014

Treatment Updates Regarding Anaplastic Oligodendroglioma And Anaplastic Oligoastrocytoma, Khurshid Ahmed Khan, Ahmed Nadeem Abbasi, Nasir Ali

Department of Radiation Oncology

Anaplastic Oligodendroglioma / Anaplastic Oligoastrocytoma (AO/AOA) is a WHO Grade-III primary brain tumor. These tumors comprise about 5 - 10% of all gliomas, which make them the third most common primary brain tumors after glioblastoma multiforme and astrocytomas. For many years standard of treatment remained Maximum Safe Resection (MSR) followed by Radiotherapy (RT). These tumors have also been known to be sensitive to alkylator-based chemotherapy particularly the subset having 1p/19q co-deletion signature. There is robust data showing that these tumors are responsive to chemotherapy in recurrent or progressive setting. Recently, up front chemotherapy has been added to standard post-surgery RT. …


Vaccine Effectiveness And Risk Factors Associated With Measles Among Children Presenting To The Hospitals Of Karachi, Pakistan., Aysha Zahidie, Saba Wasim, Zafar Fatmi Dec 2014

Vaccine Effectiveness And Risk Factors Associated With Measles Among Children Presenting To The Hospitals Of Karachi, Pakistan., Aysha Zahidie, Saba Wasim, Zafar Fatmi

Community Health Sciences

OBJECTIVE:

To determine the risk factors regarding guardian's practices associated with development of Measles and also find out effectiveness of Measles vaccine among children less than 12 years of age presenting to the hospitals of Karachi.

STUDY DESIGN:

Matched case control study.

PLACE AND DURATION OF STUDY:

Multicenter surveillance was conducted in 11 public and private sector hospitals of Karachi from January 2011 to September 2012 in consultation with World Health Organization Measles Surveillance Cell.

METHODOLOGY:

Cases were children aged less than 12 years with Measles presenting to the hospitals. Controls for cases were enrolled from the same hospitals without …


A Combined Therapeutic Regimen Of Buspirone And Environmental Enrichment Is More Efficacrious Than Either Alone In Enhancing Spatial Learning In Brain-Injured Rats, Christina M. Monaco, Kory M. Gebhardt, Sarah M. Chlebowski, Kaitlyn E. Shaw, Jeffrey P. Cheng Dec 2014

A Combined Therapeutic Regimen Of Buspirone And Environmental Enrichment Is More Efficacrious Than Either Alone In Enhancing Spatial Learning In Brain-Injured Rats, Christina M. Monaco, Kory M. Gebhardt, Sarah M. Chlebowski, Kaitlyn E. Shaw, Jeffrey P. Cheng

PCOM Scholarly Works

Abstract Buspirone, a 5-HT1A receptor agonist, and environmental enrichment (EE) enhance cognition and reduce histopathology after traumatic brain injury (TBI) in adult rats, but have not been fully evaluated after pediatric TBI, which is the leading cause of death in children. Hence, the aims of this study were to assess the efficacy of buspirone alone (Experiment 1) and in combination with EE (Experiment 2) in TBI postnatal day-17 male rats. The hypothesis was that both therapies would confer cognitive and histological benefits when provided singly, but their combination would be more efficacious. Anesthetized rats received a cortical impact or sham …


Emerging Antiretroviral Drug Resistance In Sub-Saharan Africa: Novel Affordable Technologies Are Needed To Provide Resistance Testing For Individual And Public Health Benefits, Gert U. Van Zyl, Lisa M. Frenkel, Michael Chung, Wolfgang Preiser, John W. Mellors, Jean B. Nachega Nov 2014

Emerging Antiretroviral Drug Resistance In Sub-Saharan Africa: Novel Affordable Technologies Are Needed To Provide Resistance Testing For Individual And Public Health Benefits, Gert U. Van Zyl, Lisa M. Frenkel, Michael Chung, Wolfgang Preiser, John W. Mellors, Jean B. Nachega

Internal Medicine, East Africa

In industrialized countries, viral load monitoring and genotypic antiretroviral drug resistance testing (GART) play an important role in the selection of initial and subsequent combination antiretroviral therapy (cART) regimens. In contrast, resource constraints in Africa limit access to assays that could detect virologic failure, transmitted drug resistance (TDR) and acquired drug resistance to cART. This has adverse consequences for both individual and public health. Although the further roll-out of antiretrovirals for prevention, including preexposure prophylaxis (PrEP) and universal test and treat (UTT) strategies, could reduce HIV-1 incidence, these strategies may increase TDR [1,2]. Here, we present arguments that the scale …


Surface Attachment Induces Pseudomonas Aeruginosa Virulence, Albert Siryaporn, Sherry L. Kuchma, George A. Ou2019toole, Zemer Gitai Nov 2014

Surface Attachment Induces Pseudomonas Aeruginosa Virulence, Albert Siryaporn, Sherry L. Kuchma, George A. Ou2019toole, Zemer Gitai

Dartmouth Scholarship

Pseudomonas aeruginosa infects every type of host that has been examined by deploying multiple virulence factors. Previous studies of virulence regulation have largely focused on chemical cues, but P. aeruginosa may also respond to mechanical cues. Using a rapid imaging-based virulence assay, we demonstrate that P. aeruginosa activates virulence in response to attachment to a range of chemically distinct surfaces, suggesting that this bacterial species responds to mechanical properties of its substrates. Surface-activated virulence requires quorum sensing, but activating quorum sensing does not induce virulence without surface attachment. The activation of virulence by surfaces also requires the surface-exposed protein PilY1, …


The Emerging Roles Of Gprc5a In Diseases., Honglei Zhou, Isidore Rigoutsos Nov 2014

The Emerging Roles Of Gprc5a In Diseases., Honglei Zhou, Isidore Rigoutsos

Computational Medicine Center Faculty Papers

The 'Retinoic Acid-Inducible G-protein-coupled receptors' or RAIG are a group comprising the four orphan receptors GPRC5A, GPRC5B, GPRC5C and GPRC5D. As the name implies, their expression is induced by retinoic acid but beyond that very little is known about their function. In recent years, one member, GPRC5A, has been receiving increasing attention as it was shown to play important roles in human cancers. As a matter of fact, dysregulation of GPRC5A has been associated with several cancers including lung cancer, breast cancer, colorectal cancer, and pancreatic cancer. Here we review the current state of knowledge about the heterogeneity and evolution …


The Long Non-Coding Rna Pcat-1 Promotes Prostate Cancer Cell Proliferation Through Cmyc., John R. Prensner, Wei Chen, Sumin Han, Matthew K. Iyer, Qi Cao, Vishal Kothari, Joseph R. Evans, Karen E. Knudsen, Michelle T. Paulsen, Mats Ljungman, Theodore S. Lawrence, Arul M. Chinnaiyan, Felix Y. Feng Nov 2014

The Long Non-Coding Rna Pcat-1 Promotes Prostate Cancer Cell Proliferation Through Cmyc., John R. Prensner, Wei Chen, Sumin Han, Matthew K. Iyer, Qi Cao, Vishal Kothari, Joseph R. Evans, Karen E. Knudsen, Michelle T. Paulsen, Mats Ljungman, Theodore S. Lawrence, Arul M. Chinnaiyan, Felix Y. Feng

Department of Cancer Biology Faculty Papers

Long non-coding RNAs (lncRNAs) represent an emerging layer of cancer biology, contributing to tumor proliferation, invasion, and metastasis. Here, we describe a role for the oncogenic lncRNA PCAT-1 in prostate cancer proliferation through cMyc. We find that PCAT-1-mediated proliferation is dependent on cMyc protein stabilization, and using expression profiling, we observed that cMyc is required for a subset of PCAT-1-induced expression changes. The PCAT-1-cMyc relationship is mediated through the post-transcriptional activity of the MYC 3' untranslated region, and we characterize a role for PCAT-1 in the disruption of MYC-targeting microRNAs. To further elucidate a role for post-transcriptional regulation, we demonstrate …


Swelling And Eicosanoid Metabolites Differentially Gate Trpv4 Channels In Retinal Neurons And Glia., Daniel A. Ryskamp, Andrew O. Jo, Amber M M. Frye, Felix Vazquez-Chona, Nanna Macaulay, Wallace B. Thoreson, David Križaj Nov 2014

Swelling And Eicosanoid Metabolites Differentially Gate Trpv4 Channels In Retinal Neurons And Glia., Daniel A. Ryskamp, Andrew O. Jo, Amber M M. Frye, Felix Vazquez-Chona, Nanna Macaulay, Wallace B. Thoreson, David Križaj

Journal Articles: Ophthalmology

Activity-dependent shifts in ionic concentrations and water that accompany neuronal and glial activity can generate osmotic forces with biological consequences for brain physiology. Active regulation of osmotic gradients and cellular volume requires volume-sensitive ion channels. In the vertebrate retina, critical support to volume regulation is provided by Müller astroglia, but the identity of their osmosensor is unknown. Here, we identify TRPV4 channels as transducers of mouse Müller cell volume increases into physiological responses. Hypotonic stimuli induced sustained [Ca(2+)]i elevations that were inhibited by TRPV4 antagonists and absent in TRPV4(-/-) Müller cells. Glial TRPV4 signals were phospholipase A2- and cytochrome P450-dependent, …


Camk2n1 Inhibits Prostate Cancer Progression Through Androgen Receptor-Dependent Signaling., Tao Wang, Shuiming Guo, Zhuo Liu, Licheng Wu, Mingchao Li, Jun Yang, Ruibao Chen, Xiaming Liu, Hua Xu, Shaoxin Cai, Hui Chen, Weiyong Li, Shaohua Xu, Liang Wang, Zhiquan Hu, Qianyuan Zhuang, Liping Wang, Kongming Wu, Jihong Liu, Zhangqun Ye, Jun-Yuan Ji, Chenguang Wang, Ke Chen Nov 2014

Camk2n1 Inhibits Prostate Cancer Progression Through Androgen Receptor-Dependent Signaling., Tao Wang, Shuiming Guo, Zhuo Liu, Licheng Wu, Mingchao Li, Jun Yang, Ruibao Chen, Xiaming Liu, Hua Xu, Shaoxin Cai, Hui Chen, Weiyong Li, Shaohua Xu, Liang Wang, Zhiquan Hu, Qianyuan Zhuang, Liping Wang, Kongming Wu, Jihong Liu, Zhangqun Ye, Jun-Yuan Ji, Chenguang Wang, Ke Chen

Department of Cancer Biology Faculty Papers

Castration resistance is a major obstacle to hormonal therapy for prostate cancer patients. Although androgen independence of prostate cancer growth is a known contributing factor to endocrine resistance, the mechanism of androgen receptor deregulation in endocrine resistance is still poorly understood. Herein, the CAMK2N1 was shown to contribute to the human prostate cancer cell growth and survival through AR-dependent signaling. Reduced expression of CAMK2N1 was correlated to recurrence-free survival of prostate cancer patients with high levels of AR expression in their tumor. CAMK2N1 and AR signaling form an auto-regulatory negative feedback loop: CAMK2N1 expression was down-regulated by AR activation; while …


The Induction Of The P53 Tumor Suppressor Protein Bridges The Apoptotic And Autophagic Signaling Pathways To Regulate Cell Death In Prostate Cancer Cells., Lymor Ringer, Paul Sirajuddin, Lucas Tricoli, Sarah Waye, Muhammad Umer Choudhry, Erika Parasido, Angiela Sivakumar, Mary Heckler, Aisha Naeem, Iman Abdelgawad, Xuefeng Liu, Adam S Feldman, Richard J Lee, Chin-Lee Wu, Venkata Yenugonda, Bhaskar Kallakury, Anatoly Dritschilo, John Lynch, Richard Schlegel, Olga Rodriguez, Richard Pestell, Maria Laura Avantaggiati, Chris Albanese Nov 2014

The Induction Of The P53 Tumor Suppressor Protein Bridges The Apoptotic And Autophagic Signaling Pathways To Regulate Cell Death In Prostate Cancer Cells., Lymor Ringer, Paul Sirajuddin, Lucas Tricoli, Sarah Waye, Muhammad Umer Choudhry, Erika Parasido, Angiela Sivakumar, Mary Heckler, Aisha Naeem, Iman Abdelgawad, Xuefeng Liu, Adam S Feldman, Richard J Lee, Chin-Lee Wu, Venkata Yenugonda, Bhaskar Kallakury, Anatoly Dritschilo, John Lynch, Richard Schlegel, Olga Rodriguez, Richard Pestell, Maria Laura Avantaggiati, Chris Albanese

Kimmel Cancer Center Faculty Papers

The p53 tumor suppressor protein plays a crucial role in influencing cell fate decisions in response to cellular stress. As p53 elicits cell cycle arrest, senescence or apoptosis, the integrity of the p53 pathway is considered a key determinant of anti-tumor responses. p53 can also promote autophagy, however the role of p53-dependent autophagy in chemosensitivity is poorly understood. VMY-1-103 (VMY), a dansylated analog of purvalanol B, displays rapid and potent anti-tumor activities, however the pathways by which VMY works are not fully defined. Using established prostate cancer cell lines and novel conditionally reprogrammed cells (CRCs) derived from prostate cancer patients; …


Connecting Undergraduate Science Education With The Needs Of Today's Graduates, Viviane Callier, Richard H. Singiser, Nathan L. Vanderford Nov 2014

Connecting Undergraduate Science Education With The Needs Of Today's Graduates, Viviane Callier, Richard H. Singiser, Nathan L. Vanderford

Markey Cancer Center Faculty Publications

Undergraduate science programs are not providing graduates with the knowledgebase and skills they need to be successful on today’s job market. Curricular changes relevant to today’s marketplace and more opportunities for internships and work experience during students’ secondary education would facilitate a smoother transition to the working world and help employers find graduates that possess both the hard and soft skills needed in the workplace. In this article, we discuss these issues and offer solutions that would generate more marketplace-ready undergraduates.


Alzheimer's Therapeutics Targeting Amyloid Beta 1-42 Oligomers I: Abeta 42 Oligomer Binding To Specific Neuronal Receptors Is Displaced By Drug Candidates That Improve Cognitive Deficits, Nicholas J. Izzo, Agnes Staniszewski, Lillian To, Mauro Fa, Andrew F. Teich, Faisal Saeed, Harrison Wostein, Thomas Walko Iii, Anisha Vaswani, Meghan Wardius, Zanobia Syed, Jessica Ravenscroft, Kelsie Mozzoni, Colleen Silky, Courtney Rehak, Raymond Yurko, Patricia Finn, Gary Look, Gilbert Rishton, Hank Safferstein, Miles Miller, Conrad Johanson, Edward Stopa, Manfred Windisch, Birgit Hutter-Paier, Mehrdad Shamloo, Ottavio Arancio, Harry Levine Iii, Susan M. Catalano Nov 2014

Alzheimer's Therapeutics Targeting Amyloid Beta 1-42 Oligomers I: Abeta 42 Oligomer Binding To Specific Neuronal Receptors Is Displaced By Drug Candidates That Improve Cognitive Deficits, Nicholas J. Izzo, Agnes Staniszewski, Lillian To, Mauro Fa, Andrew F. Teich, Faisal Saeed, Harrison Wostein, Thomas Walko Iii, Anisha Vaswani, Meghan Wardius, Zanobia Syed, Jessica Ravenscroft, Kelsie Mozzoni, Colleen Silky, Courtney Rehak, Raymond Yurko, Patricia Finn, Gary Look, Gilbert Rishton, Hank Safferstein, Miles Miller, Conrad Johanson, Edward Stopa, Manfred Windisch, Birgit Hutter-Paier, Mehrdad Shamloo, Ottavio Arancio, Harry Levine Iii, Susan M. Catalano

Sanders-Brown Center on Aging Faculty Publications

Synaptic dysfunction and loss caused by age-dependent accumulation of synaptotoxic beta amyloid (Abeta) 1-42 oligomers is proposed to underlie cognitive decline in Alzheimer's disease (AD). Alterations in membrane trafficking induced by Abeta oligomers mediates reduction in neuronal surface receptor expression that is the basis for inhibition of electrophysiological measures of synaptic plasticity and thus learning and memory. We have utilized phenotypic screens in mature, in vitro cultures of rat brain cells to identify small molecules which block or prevent the binding and effects of Abeta oligomers. Synthetic Abeta oligomers bind saturably to a single site on neuronal synapses and induce …


Alzheimer's Therapeutics Targeting Amyloid Beta 1–42 Oligomers Ii: Sigma-2/Pgrmc1 Receptors Mediate Abeta 42 Oligomer Binding And Synaptotoxicity, Nicholas J. Izzo, Jinbin Xu, Chenbo Zeng, Molly J. Kirk, Kelsie Mozzoni, Colleen Silky, Courtney Rehak, Raymond Yurko, Gary Look, Gilbert Rishton, Hank Safferstein, Carlos Cruchaga, Alison Goate, Michael A. Cahill, Ottavio Arancio, Robert H. Mach, Rolf Craven, Elizabeth Head, Harry Levine Iii, Tara L. Spires-Jones, Susan M. Catalano Nov 2014

Alzheimer's Therapeutics Targeting Amyloid Beta 1–42 Oligomers Ii: Sigma-2/Pgrmc1 Receptors Mediate Abeta 42 Oligomer Binding And Synaptotoxicity, Nicholas J. Izzo, Jinbin Xu, Chenbo Zeng, Molly J. Kirk, Kelsie Mozzoni, Colleen Silky, Courtney Rehak, Raymond Yurko, Gary Look, Gilbert Rishton, Hank Safferstein, Carlos Cruchaga, Alison Goate, Michael A. Cahill, Ottavio Arancio, Robert H. Mach, Rolf Craven, Elizabeth Head, Harry Levine Iii, Tara L. Spires-Jones, Susan M. Catalano

Sanders-Brown Center on Aging Faculty Publications

Amyloid beta (Abeta) 1-42 oligomers accumulate in brains of patients with Mild Cognitive Impairment (MCI) and disrupt synaptic plasticity processes that underlie memory formation. Synaptic binding of Abeta oligomers to several putative receptor proteins is reported to inhibit long-term potentiation, affect membrane trafficking and induce reversible spine loss in neurons, leading to impaired cognitive performance and ultimately to anterograde amnesia in the early stages of Alzheimer's disease (AD). We have identified a receptor not previously associated with AD that mediates the binding of Abeta oligomers to neurons, and describe novel therapeutic antagonists of this receptor capable of blocking Abeta toxic …


Corticosteroids And Pediatric Septic Shock Outcomes: A Risk Stratified Analysis, Sarah J. Atkinson, Natalie Z. Cvijanovich, Neal J. Thomas, Geoffrey L. Allen, Nick Anas, Robert J. Freishtat, +17 Additional Authors Nov 2014

Corticosteroids And Pediatric Septic Shock Outcomes: A Risk Stratified Analysis, Sarah J. Atkinson, Natalie Z. Cvijanovich, Neal J. Thomas, Geoffrey L. Allen, Nick Anas, Robert J. Freishtat, +17 Additional Authors

Pediatrics Faculty Publications

Background

The potential benefits of corticosteroids for septic shock may depend on initial mortality risk.

Objective

We determined associations between corticosteroids and outcomes in children with septic shock who were stratified by initial mortality risk.

Methods

We conducted a retrospective analysis of an ongoing, multi-center pediatric septic shock clinical and biological database. Using a validated biomarker-based stratification tool (PERSEVERE), 496 subjects were stratified into three initial mortality risk strata (low, intermediate, and high). Subjects receiving corticosteroids during the initial 7 days of admission (n = 252) were compared to subjects who did not receive corticosteroids (n = 244). Logistic regression …


On Reporting The Onset Of The Intention To Move, Uri Maoz, Liad Mudrik, Ram Rivlin, Ian Ross, Adam Mamelak, Gideon Yaffe Nov 2014

On Reporting The Onset Of The Intention To Move, Uri Maoz, Liad Mudrik, Ram Rivlin, Ian Ross, Adam Mamelak, Gideon Yaffe

Psychology Faculty Books and Book Chapters

"In 1965, Hans Kornhuber and Luder Deecke made a discovery that greatly influenced the study of voluntary action. Using electroencephalography (EEG), they showed that when aligning some tens of trials to movement onset and averaging, a slowly decreasing electrical potential emerges over central regions of the brain. It starts 1 second ( s) or so before the onset of the voluntary action1 and continues until shortly after the action begins. They termed this the Bereitschaftspotential, or readiness potential (RP; Kornhuber & Deecke, 1965).2 This became the first well-established neural marker of voluntary action. In that, the RP allowed for more …


Self-Propagative Replication Of Aβ Oligomers Suggests Potential Transmissibility In Alzheimer Disease, Amit Kumar, Kayla M. Pate, Melissa A. Moss, Dexter N. Dean, Vijayaraghavan Rangachari Nov 2014

Self-Propagative Replication Of Aβ Oligomers Suggests Potential Transmissibility In Alzheimer Disease, Amit Kumar, Kayla M. Pate, Melissa A. Moss, Dexter N. Dean, Vijayaraghavan Rangachari

Faculty Publications

The aggregation of amyloid-β (Aβ) peptide and its deposition in parts of the brain form the central processes in the etiology of Alzheimer disease (AD). The low-molecular weight oligomers of Aβ aggregates (2 to 30 mers) are known to be the primary neurotoxic agents whose mechanisms of cellular toxicity and synaptic dysfunction have received substantial attention in the recent years. However, how these toxic agents proliferate and induce widespread amyloid deposition throughout the brain, and what mechanism is involved in the amplification and propagation of toxic oligomer species, are far from clear. Emerging evidence based on transgenic mice models indicates …


Autoantibodies To The Ny-Eso-1 Tumor Antigen In Metastatic Melanoma: Sialylation Of The Fc Region Of Immunoglobulin G Induces Differential Expression Signatures Of Inflammatory Molecules During Dendritic Cell Differentiation And Maturation, Martin Oaks, Nathaniel Rein, John O. Richards, James Shaffer Nov 2014

Autoantibodies To The Ny-Eso-1 Tumor Antigen In Metastatic Melanoma: Sialylation Of The Fc Region Of Immunoglobulin G Induces Differential Expression Signatures Of Inflammatory Molecules During Dendritic Cell Differentiation And Maturation, Martin Oaks, Nathaniel Rein, John O. Richards, James Shaffer

Journal of Patient-Centered Research and Reviews

Purpose: We tested the hypothesis that different glycoforms of antibodies from patients with metastatic melanoma have different functional effects on human dendritic cell differentiation and maturation.

Methods: Antibodies to the cancer antigen NY-ESO-1 were affinity-purified from patients with melanoma and further fractionated into different glycoforms by lectin chromatography. Sialic acid-rich and sialic acid-poor fractions of these immunoglobulin G antibodies (IgG) were added to dendritic cell cultures during both differentiation and maturation, and the resulting cellular messenger RNA (mRNA) and culture supernatants were tested by microarray and enzyme-linked immunoassay for molecules related to inflammatory pathways.

Results: We identified unique mRNA and …


The Translational Biology Of Remyelination: Past, Present, And Future, Robin J.M. Franklin, Vittorio Gallo Nov 2014

The Translational Biology Of Remyelination: Past, Present, And Future, Robin J.M. Franklin, Vittorio Gallo

Pediatrics Faculty Publications

Amongst neurological diseases, multiple sclerosis (MS) presents an attractive target for regenerative medicine. This is because the primary pathology, the loss of myelin-forming oligodendrocytes, can be followed by a spontaneous and efficient regenerative process called remyelination. While cell transplantation approaches have been explored as a means of replacing lost oligodendrocytes, more recently therapeutic approaches that target the endogenous regenerative process have been favored. This is in large part due to our increasing understanding of (1) the cell types within the adult brain that are able to generate new oligodendrocytes, (2) the mechanisms and pathways by which this achieved, and (3) …


Atrx Is Required For Maintenance Of The Neuroprogenitor Cell Pool In The Embryonic Mouse Brain, Kieran Ritchie, L Ashley Watson, Benjamin Davidson, Yan Jiang, Nathalie G. Bérubé Nov 2014

Atrx Is Required For Maintenance Of The Neuroprogenitor Cell Pool In The Embryonic Mouse Brain, Kieran Ritchie, L Ashley Watson, Benjamin Davidson, Yan Jiang, Nathalie G. Bérubé

Paediatrics Publications

Mutations in the alpha-thalassemia mental retardation X-linked (ATRX) gene cause a spectrum of abnormalities including intellectual disability, developmental delay, seizures, and microcephaly. The ATRX protein is highly enriched at heterochromatic repetitive sequences adjacent to the centromere, and ATRX depletion results in chromosome congression, segregation, and cohesion defects. Here, we show that Cre-mediated inactivation of Atrx in the embryonic mouse (Mus musculus) brain results in expansion of cerebral cortical layer VI, and a concurrent thinning of layers II-IV. We observed increased cell cycle exit during early-mid neurogenesis, and a depletion of apical progenitors by late neurogenesis in the Atrx-null neocortex, explaining …


Hormone Whodunit: Clues For Solving The Case Of Intratumor Androgen Production., Karen E Knudsen Nov 2014

Hormone Whodunit: Clues For Solving The Case Of Intratumor Androgen Production., Karen E Knudsen

Department of Cancer Biology Faculty Papers

One of the key mechanisms by which prostate cancer cells evade hormone therapy is through intratumor testosterone production. New evidence points toward androstenedione as a potential precursor of intratumor androgen production and furthers nomination of AKR1C3 as a therapeutic target in advanced disease. Clin Cancer Res; 20(21); 5343-5. ©2014 AACR.


Oncolog, Volume 59, Number 11-12, November-December 2014, Bryan Tutt, Sunita Patterson, S. Moreau Nov 2014

Oncolog, Volume 59, Number 11-12, November-December 2014, Bryan Tutt, Sunita Patterson, S. Moreau

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

  • Striving to Improve Treatments for Uveal Melanoma: Although primary uveal melanoma can be effectively treated with radiation or surgery, patients with metastatic disease-or those at high risk for metastases-have few proven options. But specialists in medical oncology, radiation oncology, ophthalmology, surgery, and traditional research are working to improve those options
  • Beyond Diabetes: Metformin May Have Broad Utility in Cancer: Metformin, an inexpensive drug that has been prescribed for diabetes for decades, may also be useful in preventing or treating several types of cancer
  • HOUSE CALL: Smoking Cessation-Medications help smokers quit
  • INBRIEF: Vaccine Explored to Reduce Risk of HER2-Positive Breast Cancer …


Hypoxic Stress Induces, But Cannot Sustain Trophoblast Stem Cell Differentiation To Labyrinthine Placenta Due To Mitochondrial Insufficiency, Yufen Xie, Sichang Zhou, Zhongliang Jiang, Jing Dai, Elizabeth E. Puscheck, Icksoo Lee, Graham Parker, Maik Hüttemann, Daniel A. Rappolee Nov 2014

Hypoxic Stress Induces, But Cannot Sustain Trophoblast Stem Cell Differentiation To Labyrinthine Placenta Due To Mitochondrial Insufficiency, Yufen Xie, Sichang Zhou, Zhongliang Jiang, Jing Dai, Elizabeth E. Puscheck, Icksoo Lee, Graham Parker, Maik Hüttemann, Daniel A. Rappolee

Department of Obstetrics and Gynecology Research Publications

Dysfunctional stem cell differentiation into placental lineages is associated with gestational diseases. Of the differentiated lineages available to trophoblast stem cells (TSC), elevated O2 and mitochondrial function are necessary to placental lineages at the maternal–placental surface and important in the etiology of preeclampsia. TSC lineage imbalance leads to embryonic failure during uterine implantation. Stress at implantation exacerbates stem cell depletion by decreasing proliferation and increasing differentiation. In an implantation site O2 is normally ~ 2%. In culture, exposure to 2% O2 and fibroblast growth factor 4 (FGF4) enabled the highest mouse TSC multipotency and proliferation. In contrast, hypoxic stress (0.5% …


Oligonucleotide Ligation Assay Detects Hiv Drug Resistance Associated With Virologic Failure Among Antiretroviral-Naive Adults In Kenya, Michael Chung, Ingrid A. Beck, Sandra Dross, Kenneth Tapia, James N. Kiarie, Barbra A. Richardson, Julie Overbaugh, Samah R. Sakr, Grace C. John-Stewart, Lisa M. Frenkel Nov 2014

Oligonucleotide Ligation Assay Detects Hiv Drug Resistance Associated With Virologic Failure Among Antiretroviral-Naive Adults In Kenya, Michael Chung, Ingrid A. Beck, Sandra Dross, Kenneth Tapia, James N. Kiarie, Barbra A. Richardson, Julie Overbaugh, Samah R. Sakr, Grace C. John-Stewart, Lisa M. Frenkel

Internal Medicine, East Africa

Background: Transmitted drug resistance (TDR) is increasing in some areas of Africa. Detection of TDR may predict virologic failure of first-line non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART). We evaluated the utility of a relatively inexpensive oligonucleotide ligation assay (OLA) to detect clinically relevant TDR at time of ART initiation.

Methods: Pre-ART plasmas from ART-naive Kenyans initiating an NNRTI-based fixed-dose combination ART in a randomized adherence trial conducted in 2006 were retrospectively analyzed by OLA for mutations conferring resistance to NNRTI (K103N, Y181C, and G190A) and lamivudine (M184V). Post-ART plasmas were analyzed for virologic failure (≥1,000 copies/mL) at 6 month …


Adult Neurogenesis In The Four-Striped Mice (Rhabdomys Pumilio), Olatunbosun O. Olaleye, Amadi O. Ihunwo Nov 2014

Adult Neurogenesis In The Four-Striped Mice (Rhabdomys Pumilio), Olatunbosun O. Olaleye, Amadi O. Ihunwo

Brain and Mind Institute

In this study, we investigated non-captive four-striped mice (Rhabdomys pumilio) for evidence that adult neurogenesis occurs in the adult brain of animal models in natural environment. Ki-67 (a marker for cell proliferation) and doublecortin (a marker for immature neurons) immunostaining confirmed that adult neurogenesis occurs in the active sites of subventricular zone of the lateral ventricle with the migratory stream to the olfactory bulb, and the subgranular zone of the dentate gyrus of the hippocampus. No Ki-67 proliferating cells were observed in the striatum substantia nigra, amygdala, cerebral cortex or dorsal vagal complex. Doublecortin-immunoreactive cells were observed in …


Acidosis Potentiates The Host Proinflammatory Interleukin-1Β Response To Pseudomonas Aeruginosa Infection, I. M. Torres, Y. R. Patankar, Tamer B. Shabaneh, E. Dolben, Deborah Hogan, David Leib, Brent L. Berwin Nov 2014

Acidosis Potentiates The Host Proinflammatory Interleukin-1Β Response To Pseudomonas Aeruginosa Infection, I. M. Torres, Y. R. Patankar, Tamer B. Shabaneh, E. Dolben, Deborah Hogan, David Leib, Brent L. Berwin

Dartmouth Scholarship

Infection by Pseudomonas aeruginosa, and bacteria in general, frequently promotes acidification of the local microenvironment, and this is reinforced by pulmonary exertion and exacerbation. However, the consequence of an acidic environment on the host inflammatory response to P. aeruginosa infection is poorly understood. Here we report that the pivotal cellular and host proinflammatory interleukin-1β (IL-1β) response, which enables host clearance of the infection but can produce collateral inflammatory damage, is increased in response to P. aeruginosa infection within an acidic environment. Synergistic mechanisms that promote increased IL-1β release in response to P. aeruginosa infection in an acidic environment are …


Mouse Hepatitis Virus Infection Upregulates Genes Involved In Innate Immune Responses., Dhriti Chatterjee, Sankar Addya, Reas S Khan, Lawrence C. Kenyon, Alexander Choe, Randall J Cohrs, Kenneth S Shindler, Jayasri Das Sarma Oct 2014

Mouse Hepatitis Virus Infection Upregulates Genes Involved In Innate Immune Responses., Dhriti Chatterjee, Sankar Addya, Reas S Khan, Lawrence C. Kenyon, Alexander Choe, Randall J Cohrs, Kenneth S Shindler, Jayasri Das Sarma

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Neurotropic recombinant strain of Mouse Hepatitis Virus, RSA59, induces meningo-encephalitis, myelitis and demyelination following intracranial inoculation. RSA59 induced neuropathology is partially caused by activation of CNS resident microglia, as demonstrated by changes in cellular morphology and increased expression of a microglia/macrophage specific calcium ion binding factor, Iba1. Affymetrix Microarray analysis for mRNA expression data reveals expression of inflammatory mediators that are known to be released by activated microglia. Microglia-specific cell surface molecules, including CD11b, CD74, CD52 and CD68, are significantly upregulated in contrast to CD4, CD8 and CD19. Protein analysis of spinal cord extracts taken from mice 6 days post-inoculation, …


Ectopic Cushing Syndrome And Pancreatic Cancer: A Case Report, Mira Mitry Md, Nicole M. Agostino Do, Stacey Smith Md, Facp, Vasudev G. Magaji Md, Ms Oct 2014

Ectopic Cushing Syndrome And Pancreatic Cancer: A Case Report, Mira Mitry Md, Nicole M. Agostino Do, Stacey Smith Md, Facp, Vasudev G. Magaji Md, Ms

Department of Medicine

No abstract provided.


Mechanisms Of T-B Cell Cooperation Important For Mog Antibody Mediated Demyelination, Dusanka S. Skundric Oct 2014

Mechanisms Of T-B Cell Cooperation Important For Mog Antibody Mediated Demyelination, Dusanka S. Skundric

Neurology Faculty Publications

No abstract provided.