Open Access. Powered by Scholars. Published by Universities.®

Medicine and Health Sciences Commons

Open Access. Powered by Scholars. Published by Universities.®

Medical Specialties

PDF

2014

Humans

Institution
Publication
Publication Type

Articles 1 - 30 of 168

Full-Text Articles in Medicine and Health Sciences

Classification Of Current Anticancer Immunotherapies., Lorenzo Galluzzi, Erika Vacchelli, José-Manuel Bravo-San Pedro, Aitziber Buqué, Laura Senovilla, Elisa Elena Baracco, Norma Bloy, Francesca Castoldi, Jean-Pierre Abastado, Patrizia Agostinis, Ron N. Apte, Fernando Aranda, Maha Ayyoub, Philipp Beckhove, Jean-Yves Blay, Laura Bracci, Anne Caignard, Chiara Castelli, Federica Cavallo, Estaban Celis, Vincenzo Cerundolo, Aled Clayton, Mario P. Colombo, Lisa Coussens, Madhav V. Dhodapkar, Alexander M. Eggermont, Douglas T. Fearon, Wolf H. Fridman, Jitka Fučíková, Dmitry I. Gabrilovich, Jérôme Galon, Abhishek Garg, François Ghiringhelli, Giuseppe Giaccone, Eli Gilboa, Sacha Gnjatic, Axel Hoos, Anne Hosmalin, Dirk Jäger, Pawel Kalinski, Klas Kärre, Oliver Kepp, Rolf Kiessling, John M. Kirkwood, Eva Klein, Alexander Knuth, Claire E. Lewis, Roland Liblau, Michael T. Lotze, Enrico Lugli, Jean-Pierre Mach, Fabrizio Mattei, Domenico Mavilio, Ignacio Melero, Cornelis J. Melief, Elizabeth A. Mittendorf, Lorenzo Moretta, Adekunke Odunsi, Hideho Okada, Anna Karolina Palucka, Marcus E. Peter, Kenneth J. Pienta, Angel Porgador, George C. Prendergast, Gabriel A. Rabinovich, Nicholas P. Restifo, Naiyer Rizvi, Catherine Sautès-Fridman, Hans Schreiber, Barbara Seliger, Hiroshi Shiku, Bruno Silva-Santos, Mark J. Smyth, Daniel E. Speiser, Radek Spisek, Pramod K. Srivastava, James E. Talmadge, Eric Tartour, Sjoerd H. Van Der Burg, Benoît J. Van Den Eynde, Richard Vile, Hermann Wagner, Jeffrey S. Weber, Theresa L. Whiteside, Jedd D. Wolchok, Laurence Zitvogel, Weiping Zou, Guido Kroemer Dec 2014

Classification Of Current Anticancer Immunotherapies., Lorenzo Galluzzi, Erika Vacchelli, José-Manuel Bravo-San Pedro, Aitziber Buqué, Laura Senovilla, Elisa Elena Baracco, Norma Bloy, Francesca Castoldi, Jean-Pierre Abastado, Patrizia Agostinis, Ron N. Apte, Fernando Aranda, Maha Ayyoub, Philipp Beckhove, Jean-Yves Blay, Laura Bracci, Anne Caignard, Chiara Castelli, Federica Cavallo, Estaban Celis, Vincenzo Cerundolo, Aled Clayton, Mario P. Colombo, Lisa Coussens, Madhav V. Dhodapkar, Alexander M. Eggermont, Douglas T. Fearon, Wolf H. Fridman, Jitka Fučíková, Dmitry I. Gabrilovich, Jérôme Galon, Abhishek Garg, François Ghiringhelli, Giuseppe Giaccone, Eli Gilboa, Sacha Gnjatic, Axel Hoos, Anne Hosmalin, Dirk Jäger, Pawel Kalinski, Klas Kärre, Oliver Kepp, Rolf Kiessling, John M. Kirkwood, Eva Klein, Alexander Knuth, Claire E. Lewis, Roland Liblau, Michael T. Lotze, Enrico Lugli, Jean-Pierre Mach, Fabrizio Mattei, Domenico Mavilio, Ignacio Melero, Cornelis J. Melief, Elizabeth A. Mittendorf, Lorenzo Moretta, Adekunke Odunsi, Hideho Okada, Anna Karolina Palucka, Marcus E. Peter, Kenneth J. Pienta, Angel Porgador, George C. Prendergast, Gabriel A. Rabinovich, Nicholas P. Restifo, Naiyer Rizvi, Catherine Sautès-Fridman, Hans Schreiber, Barbara Seliger, Hiroshi Shiku, Bruno Silva-Santos, Mark J. Smyth, Daniel E. Speiser, Radek Spisek, Pramod K. Srivastava, James E. Talmadge, Eric Tartour, Sjoerd H. Van Der Burg, Benoît J. Van Den Eynde, Richard Vile, Hermann Wagner, Jeffrey S. Weber, Theresa L. Whiteside, Jedd D. Wolchok, Laurence Zitvogel, Weiping Zou, Guido Kroemer

Journal Articles: Pathology and Microbiology

During the past decades, anticancer immunotherapy has evolved from a promising therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are now approved by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, and many others are being investigated as standalone therapeutic interventions or combined with conventional treatments in clinical studies. Immunotherapies may be subdivided into "passive" and "active" based on their ability to engage the host immune system against cancer. Since the anticancer activity of most passive immunotherapeutics (including tumor-targeting monoclonal antibodies) also relies on the host immune system, this classification …


The Promise Of Novel Molecular Markers In Bladder Cancer, Jahan Miremami, Natasha Kyprianou Dec 2014

The Promise Of Novel Molecular Markers In Bladder Cancer, Jahan Miremami, Natasha Kyprianou

Urology Faculty Publications

Bladder cancer is the fourth most common malignancy in the US and is associated with the highest cost per patient. A high likelihood of recurrence, mandating stringent surveillance protocols, has made the development of urinary markers a focus of intense pursuit with the hope of decreasing the burden this disease places on patients and the healthcare system. To date, routine use of markers is not recommended for screening or diagnosis. Interests include the development of a single urinary marker that can be used in place of or as an adjunct to current screening and surveillance techniques, as well identifying a …


Dual Engagement Of The Nlrp3 And Aim2 Inflammasomes By Plasmodium-Derived Hemozoin And Dna During Malaria, Parisa Kalantari, Rosane B. Deoliveira, Jennie Chan, Yolanda Corbett, Vijay A. K. Rathinam, Andrea Stutz, Eicke Latz, Ricardo T. Gazzinelli, Douglas T. Golenbock, Katherine A. Fitzgerald Dec 2014

Dual Engagement Of The Nlrp3 And Aim2 Inflammasomes By Plasmodium-Derived Hemozoin And Dna During Malaria, Parisa Kalantari, Rosane B. Deoliveira, Jennie Chan, Yolanda Corbett, Vijay A. K. Rathinam, Andrea Stutz, Eicke Latz, Ricardo T. Gazzinelli, Douglas T. Golenbock, Katherine A. Fitzgerald

Katherine A. Fitzgerald

Hemozoin (Hz) is the crystalline detoxification product of hemoglobin in Plasmodium-infected erythrocytes. We previously proposed that Hz can carry plasmodial DNA into a subcellular compartment that is accessible to Toll-like receptor 9 (TLR9), inducing an inflammatory signal. Hz also activates the NLRP3 inflammasome in primed cells. We found that Hz appears to colocalize with DNA in infected erythrocytes, even before RBC rupture or phagolysosomal digestion. Using synthetic Hz coated in vitro with plasmodial genomic DNA (gDNA) or CpG oligodeoxynucleotides, we observed that DNA-complexed Hz induced TLR9 translocation, providing a priming and an activation signal for inflammasomes. After phagocytosis, Hz and …


Sugihara Causality Analysis Of Scalp Eeg For Detection Of Early Alzheimer's Disease, Joseph C. Mcbride, Xiaopeng Zhao, Nancy B. Munro, Greg A. Jicha, Frederick A. Schmitt, Richard J. Kryscio, Charles D. Smith, Yang Jiang Dec 2014

Sugihara Causality Analysis Of Scalp Eeg For Detection Of Early Alzheimer's Disease, Joseph C. Mcbride, Xiaopeng Zhao, Nancy B. Munro, Greg A. Jicha, Frederick A. Schmitt, Richard J. Kryscio, Charles D. Smith, Yang Jiang

Sanders-Brown Center on Aging Faculty Publications

Recently, Sugihara proposed an innovative causality concept, which, in contrast to statistical predictability in Granger sense, characterizes underlying deterministic causation of the system. This work exploits Sugihara causality analysis to develop novel EEG biomarkers for discriminating normal aging from mild cognitive impairment (MCI) and early Alzheimer's disease (AD). The hypothesis of this work is that scalp EEG based causality measurements have different distributions for different cognitive groups and hence the causality measurements can be used to distinguish between NC, MCI, and AD participants. The current results are based on 30-channel resting EEG records from 48 age-matched participants (mean age 75.7 …


Kallikrein Family Proteases Klk6 And Klk7 Are Potential Early Detection And Diagnostic Biomarkers For Serous And Papillary Serous Ovarian Cancer Subtypes., Ayala Tamir, Ushma Jag, Sreeja Sarojini, Craig Schindewolf, Takemi Tanaka, Rajendra Gharbaran, Hiren Patel, Anil Sood, Wei Hu, Ruzeen Patwa, Patrick Blake, Polina Chirina, Jin Oh Jeong, Heejin Lim, Andre Goy, Andrew Pecora, K Stephen Suh Dec 2014

Kallikrein Family Proteases Klk6 And Klk7 Are Potential Early Detection And Diagnostic Biomarkers For Serous And Papillary Serous Ovarian Cancer Subtypes., Ayala Tamir, Ushma Jag, Sreeja Sarojini, Craig Schindewolf, Takemi Tanaka, Rajendra Gharbaran, Hiren Patel, Anil Sood, Wei Hu, Ruzeen Patwa, Patrick Blake, Polina Chirina, Jin Oh Jeong, Heejin Lim, Andre Goy, Andrew Pecora, K Stephen Suh

Department of Medicine Faculty Papers

BACKGROUND: Early detection of ovarian cancer remains a challenge due to widespread metastases and a lack of biomarkers for early-stage disease. This study was conducted to identify relevant biomarkers for both laparoscopic and serum diagnostics in ovarian cancer.

METHODS: Bioinformatics analysis and expression screening in ovarian cancer cell lines were employed. Selected biomarkers were further validated in bio-specimens of diverse cancer types and ovarian cancer subtypes. For non-invasive detection, biomarker proteins were evaluated in serum samples from ovarian cancer patients.

RESULTS: Two kallikrein (KLK) serine protease family members (KLK6 and KLK7) were found to be significantly overexpressed relative to normal …


Repeated Transradial Catheterization: Feasibility, Efficacy, And Safety, Marinos A Charalambous, Savvas S Constantinides, Michael A Talias, Elpidoforos S Soteriades, Christos P Christou Dec 2014

Repeated Transradial Catheterization: Feasibility, Efficacy, And Safety, Marinos A Charalambous, Savvas S Constantinides, Michael A Talias, Elpidoforos S Soteriades, Christos P Christou

The Texas Heart Institute Journal

Transradial access is an alternative to the transfemoral approach in coronary interventions. It results in less access-site bleeding, shorter hospital stays, lower costs, and less pain for the patient. However, some authors have suggested that the transradial approach might lead to radial artery occlusion, which precludes repeated same-artery catheterizations. Using data from our center, we evaluated the feasibility, safety, and efficacy of repeated transradial catheterization.

We reviewed the 3,006 transradial catheterizations performed at our center from 2006 through 2009. Patients who had undergone at least one repeated transradial catheterization were identified, their cases monitored through 2012, and their baseline characteristics …


Brachiocephalic Artery Cannulation In Proximal Aortic Surgery That Requires Circulatory Arrest, Mehmet Unal, Oguz Yilmaz, Ilker Akar, Ilker Ince, Cemal Aslan, Fatih Koc, Haluk Kafali Dec 2014

Brachiocephalic Artery Cannulation In Proximal Aortic Surgery That Requires Circulatory Arrest, Mehmet Unal, Oguz Yilmaz, Ilker Akar, Ilker Ince, Cemal Aslan, Fatih Koc, Haluk Kafali

The Texas Heart Institute Journal

The brachiocephalic artery is an alternative cannulation site in the repair of ascending aortic lesions that require circulatory arrest. We evaluate the effectiveness and safety of this technique.

Proximal aortic surgery was performed in 32 patients from 2006 through 2012 via brachiocephalic artery cannulation and circulatory arrest. Twenty-four (75%) of the patients were men. The mean age was 48.69 ± 9.43 years (range, 30–68 yr). Twelve had type I dissection, 2 had type II dissection, and 18 had true aneurysms of the ascending aorta. All operations were performed through a median sternotomy. The arterial cannula was inserted through an 8-mm …


Aortic Valve Reconstruction With Use Of Pericardial Leaflets In Adults With Bicuspid Aortic Valve Disease: Early And Midterm Outcomes, Meong Gun Song, Hyun Suk Yang, Jong Bum Choi, Je Kyoun Shin, Hyun Keun Chee, Jun Seok Kim Dec 2014

Aortic Valve Reconstruction With Use Of Pericardial Leaflets In Adults With Bicuspid Aortic Valve Disease: Early And Midterm Outcomes, Meong Gun Song, Hyun Suk Yang, Jong Bum Choi, Je Kyoun Shin, Hyun Keun Chee, Jun Seok Kim

The Texas Heart Institute Journal

In this study, we retrospectively analyzed the outcomes of adults with bicuspid aortic valve (BAV) disease who underwent aortic valve reconstructive surgery (AVRS), consisting of replacement of the diseased BAV with 2 or 3 pericardial leaflets plus fixation of the sinotubular junction for accurate and constant leaflet coaptation. From December 2007 through April 2013, 135 consecutive patients (mean age, 49.2 ± 13.1 yr; 73.3% men) with symptomatic BAV disease underwent AVRS. Raphe was observed in 84 patients (62.2%), and the remaining 51 patients had pure BAV without raphe. A total of 122 patients (90.4%) underwent 3-leaflet reconstruction, and 13 (9.6%) …


Percutaneous Repair Of Post-Myocardial Infarction Ventricular Septal Defect: Current Approaches And Future Perspectives, Maria D Baldasare, Mark Polyakov, Glenn W Laub, Joseph T Costic, Daniel J Mccormick, Sheldon Goldberg Dec 2014

Percutaneous Repair Of Post-Myocardial Infarction Ventricular Septal Defect: Current Approaches And Future Perspectives, Maria D Baldasare, Mark Polyakov, Glenn W Laub, Joseph T Costic, Daniel J Mccormick, Sheldon Goldberg

The Texas Heart Institute Journal

Post-myocardial infarction ventricular septal defect is a devastating complication of ST-elevation myocardial infarction. Although surgical intervention is considered the gold standard for treatment, it carries high morbidity and mortality rates. We present 2 cases that illustrate the application of percutaneous closure of a post-myocardial infarction ventricular septal defect: the first in a patient who had undergone prior surgical closure and then developed a new shunt, and the second as a bridge to definitive surgery in a critically ill patient.


Anticoagulation With Bivalirudin During Deep Hypothermic Circulatory Arrest In A Patient With Heparin-Induced Thrombocytopenia, Agamemnon Pericleous, Mostafa Sadek, Mary Fitzmaurice, Constance Caldwell, Kris Natividad, Konstadinos A Plestis Dec 2014

Anticoagulation With Bivalirudin During Deep Hypothermic Circulatory Arrest In A Patient With Heparin-Induced Thrombocytopenia, Agamemnon Pericleous, Mostafa Sadek, Mary Fitzmaurice, Constance Caldwell, Kris Natividad, Konstadinos A Plestis

The Texas Heart Institute Journal

Heparin-induced thrombocytopenia is a well-recognized complication of anticoagulation with heparin. We present the case of a patient with recent heparin-induced thrombocytopenia who subsequently needed surgery on an emergency basis for acute type A aortic dissection. This article reports the successful use of bivalirudin, a direct thrombin inhibitor, as an alternative to heparin throughout cardiopulmonary bypass and deep hypothermic circulatory arrest. We contend that bivalirudin is a safe alternative to heparin when performing surgery for aortic dissection and should be considered as an option for use in patients who present with heparin-induced thrombocytopenia.


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 …


Pupillometry: A Non-Invasive Technique For Pain Assessment In Paediatric Patients., Mark A. Connelly, Jacob T. Brown, Gregory L. Kearns, Rawni A. Anderson, Shawn D. St Peter, Kathleen A. Neville Dec 2014

Pupillometry: A Non-Invasive Technique For Pain Assessment In Paediatric Patients., Mark A. Connelly, Jacob T. Brown, Gregory L. Kearns, Rawni A. Anderson, Shawn D. St Peter, Kathleen A. Neville

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Pupillometry has been used to assess pain intensity and response to analgesic medications in adults. The aim of this observational study was to explore proof of concept for the use of this technique in paediatric patients. Changes in pupil parameters before and after opioid exposure also were evaluated.

DESIGN AND SETTING: This was a single-centre, prospective study conducted at an academic paediatric medical centre.

PATIENTS: Children 9-17 years of age undergoing elective surgical correction of pectus excavatum were enrolled into a protocol approved by the human ethical committee (institutional review board).

INTERVENTIONS: Pupil size and reactivity were measured using …


Simplified Post Processing Of Cine Dense Cardiovascular Magnetic Resonance For Quantification Of Cardiac Mechanics, Jonathan D. Suever, Gregory J. Wehner, Christopher M. Haggerty, Linyuan Jing, Sean M. Hamlet, Cassi M. Binkley, Sage P. Kramer, Andrea C. Mattingly, David K. Powell, Kenneth C. Bilchick, Frederick H. Epstein, Brandon K. Fornwalt Nov 2014

Simplified Post Processing Of Cine Dense Cardiovascular Magnetic Resonance For Quantification Of Cardiac Mechanics, Jonathan D. Suever, Gregory J. Wehner, Christopher M. Haggerty, Linyuan Jing, Sean M. Hamlet, Cassi M. Binkley, Sage P. Kramer, Andrea C. Mattingly, David K. Powell, Kenneth C. Bilchick, Frederick H. Epstein, Brandon K. Fornwalt

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: Cardiovascular magnetic resonance using displacement encoding with stimulated echoes (DENSE) is capable of assessing advanced measures of cardiac mechanics such as strain and torsion. A potential hurdle to widespread clinical adoption of DENSE is the time required to manually segment the myocardium during post-processing of the images. To overcome this hurdle, we proposed a radical approach in which only three contours per image slice are required for post-processing (instead of the typical 30-40 contours per image slice). We hypothesized that peak left ventricular circumferential, longitudinal and radial strains and torsion could be accurately quantified using this simplified analysis.

METHODS …


The Omega-3 Fatty Acid Docosahexaenoic Acid Attenuates Organic Dust-Induced Airway Inflammation., Tara M. Nordgren, Taylor D. Friemel, Art J. Heires, Jill A. Poole, Todd A. Wyatt, Debra J. Romberger Nov 2014

The Omega-3 Fatty Acid Docosahexaenoic Acid Attenuates Organic Dust-Induced Airway Inflammation., Tara M. Nordgren, Taylor D. Friemel, Art J. Heires, Jill A. Poole, Todd A. Wyatt, Debra J. Romberger

Journal Articles: Pulmonary & Critical Care Med

Workers exposed to organic dusts from concentrated animal feeding operations (CAFOs) are at risk for developing airway inflammatory diseases. Available preventative and therapeutic measures for alleviating dust-induced lung disease are inadequate. Because omega-3 fatty acids can mitigate inflammatory processes, we aimed to determine whether nutritional supplementation with the omega-3 fatty acid docosahexaenoic acid (DHA) could reduce the airway inflammatory consequences of exposures to organic dust. Aqueous extracts of organic dusts from swine CAFOs (ODE) were utilized. In DHA-pretreated human bronchial epithelial cells, lung fibroblasts, monocyte cell cultures, and precision-cut murine lung slices, we found that DHA pretreatment dose-dependently decreased ODE-induced …


Wordless Intervention For Epilepsy In Learning Disabilities (Wield): Study Protocol For A Randomized Controlled Feasibility Trial, Marie-Anne Durand, Bob Gates, Georgina Parkes, Asif Zia Nov 2014

Wordless Intervention For Epilepsy In Learning Disabilities (Wield): Study Protocol For A Randomized Controlled Feasibility Trial, Marie-Anne Durand, Bob Gates, Georgina Parkes, Asif Zia

Dartmouth Scholarship

Epilepsy is the most common neurological problem that affects people with learning disabilities. The high seizure frequency, resistance to treatments, associated skills deficit and co-morbidities make the management of epilepsy particularly challenging for people with learning disabilities. The Books Beyond Words booklet for epilepsy uses images to help people with learning disabilities manage their condition and improve quality of life. Our aim is to conduct a randomized controlled feasibility trial exploring key methodological, design and acceptability issues, in order to subsequently undertake a large-scale randomized controlled trial of the Books Beyond Words booklet for epilepsy.


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 …


Inhibition Of Rac1 Gtpase Sensitizes Pancreatic Cancer Cells To Γ-Irradiation., Y Yan, Ashley L. Hein, Asserewou Etekpo, Katrina M. Burchett, Chi Lin, Charles A. Enke, Surinder K. Batra, Kenneth Cowan, M Ouellette Nov 2014

Inhibition Of Rac1 Gtpase Sensitizes Pancreatic Cancer Cells To Γ-Irradiation., Y Yan, Ashley L. Hein, Asserewou Etekpo, Katrina M. Burchett, Chi Lin, Charles A. Enke, Surinder K. Batra, Kenneth Cowan, M Ouellette

Journal Articles: Radiation Oncology

Radiation therapy is a staple treatment for pancreatic cancer. However, owing to the intrinsic radioresistance of pancreatic cancer cells, radiation therapy often fails to increase survival of pancreatic cancer patients. Radiation impedes cancer cells by inducing DNA damage, which can activate cell cycle checkpoints. Normal cells possess both a G1 and G2 checkpoint. However, cancer cells are often defective in G1 checkpoint due to mutations/alterations in key regulators of this checkpoint. Accordingly, our results show that normal pancreatic ductal cells respond to ionizing radiation (IR) with activation of both checkpoints whereas pancreatic cancer cells respond to IR with G2/M arrest …


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 …


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 …


Nerve Growth Factor Regulates Neurolymphatic Remodeling During Corneal Inflammation And Resolution., Darci M. Fink, Alicia L. Connor, Philip M. Kelley, Maria M. Steele, Michael A. Hollingsworth, Richard M. Tempero Nov 2014

Nerve Growth Factor Regulates Neurolymphatic Remodeling During Corneal Inflammation And Resolution., Darci M. Fink, Alicia L. Connor, Philip M. Kelley, Maria M. Steele, Michael A. Hollingsworth, Richard M. Tempero

Journal Articles: Eppley Institute

The cellular and physiologic mechanisms that regulate the resolution of inflammation remain poorly defined despite their widespread importance in improving inflammatory disease outcomes. We studied the resolution of two cardinal signs of inflammation-pain and swelling-by investigating molecular mechanisms that regulate neural and lymphatic vessel remodeling during the resolution of corneal inflammation. A mouse model of corneal inflammation and wound recovery was developed to study this process in vivo. Administration of nerve growth factor (NGF) increased pain sensation and inhibited neural remodeling and lymphatic vessel regression processes during wound recovery. A complementary in vivo approach, the corneal micropocket assay, revealed that …


Imp3 Expression Is Associated With Poor Outcome And Epigenetic Deregulation In Intrahepatic Cholangiocarcinoma, Yuanyuan Gao, Michelle Yang, Zhong Jiang, Bruce A. Woda, Arthur M. Mercurio, Jianjie Qin, Xinli Huang, Feng Zhang Nov 2014

Imp3 Expression Is Associated With Poor Outcome And Epigenetic Deregulation In Intrahepatic Cholangiocarcinoma, Yuanyuan Gao, Michelle Yang, Zhong Jiang, Bruce A. Woda, Arthur M. Mercurio, Jianjie Qin, Xinli Huang, Feng Zhang

Arthur M. Mercurio

IMP3 is a fetal protein not expressed in normal adult tissues. IMP3 is an oncoprotein and a useful biomarker for a variety of malignancies and is associated with reduced overall survival of a number of them. IMP3 expression and its prognostic value for patients with intrahepatic cholangiocarcinoma (ICC) have not been well investigated. The molecular mechanism underlying IMP3 expression in human cancer cells remains to be elucidated. Here we investigated IMP3 expression in ICC and adjacent nonneoplastic liver in 72 unifocal primary ICCs from a single institute by immunohistochemistry, immunoblotting, and real-time polymerase chain reaction. IMP3 was specifically expressed in …


Subspecialty Surveillance Of Long-Term Course Of Small And Moderate Muscular Ventricular Septal Defect: Heterogenous Practices, Low Yield., Erik L. Frandsen, Aswathy V. House, Yunbin Xiao, David A. Danford, Shelby Kutty Nov 2014

Subspecialty Surveillance Of Long-Term Course Of Small And Moderate Muscular Ventricular Septal Defect: Heterogenous Practices, Low Yield., Erik L. Frandsen, Aswathy V. House, Yunbin Xiao, David A. Danford, Shelby Kutty

Journal Articles: Pediatrics

BACKGROUND: No expert consensus guides practice for intensity of ongoing pediatric cardiology surveillance of hemodynamically insignificant small and moderate muscular ventricular septal defect (mVSD). Therefore, despite the well-established benign natural history of mVSD, there is potential for widely divergent follow up practices. The purpose of this investigation was to evaluate (1) variations in follow up of mVSD within an academic children's hospital based pediatric cardiology practice, and (2) the frequency of active medical or surgical management resulting from follow up of mVSD.

METHODS: We retrospectively reviewed records of 600 patients with isolated mVSD echocardiographically diagnosed between 2006 and 2012. Large …


Technical Performance Score Is Associated With Outcomes After The Norwood Procedure., Meena Nathan, Lynn A. Sleeper, Richard G. Ohye, Peter C. Frommelt, Christopher A. Caldarone, James S. Tweddell, Minmin Lu, Gail D. Pearson, J William Gaynor, Christian Pizarro, Ismee A. Williams, Steven D. Colan, Carolyn Dunbar-Masterson, Peter J. Gruber, Kevin Hill, Jennifer Hirsch-Romano, Jeffrey P. Jacobs, Jonathan R. Kaltman, S Ram Kumar, David Morales, Scott M. Bradley, Kirk Kanter, Jane W. Newburger, Pediatric Heart Network Investigators, Girish S. Shirali Nov 2014

Technical Performance Score Is Associated With Outcomes After The Norwood Procedure., Meena Nathan, Lynn A. Sleeper, Richard G. Ohye, Peter C. Frommelt, Christopher A. Caldarone, James S. Tweddell, Minmin Lu, Gail D. Pearson, J William Gaynor, Christian Pizarro, Ismee A. Williams, Steven D. Colan, Carolyn Dunbar-Masterson, Peter J. Gruber, Kevin Hill, Jennifer Hirsch-Romano, Jeffrey P. Jacobs, Jonathan R. Kaltman, S Ram Kumar, David Morales, Scott M. Bradley, Kirk Kanter, Jane W. Newburger, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

Objectives: The technical performance score (TPS) has been reported in a single center study to predict the outcomes after congenital cardiac surgery. We sought to determine the association of the TPS with outcomes in patients undergoing the Norwood procedure in the Single Ventricle Reconstruction trial.

Methods: We calculated the TPS (class 1, optimal; class 2, adequate; class 3, inadequate) according to the predischarge echocardiograms analyzed in a core laboratory and unplanned reinterventions that occurred before discharge from the Norwood hospitalization. Multivariable regression examined the association of the TPS with interval to first extubation, Norwood length of stay, death or transplantation, …


The Significance Of Functional Renal Obstruction In Predicting Pathologic Stage Of Upper Tract Urothelial Carcinoma., Michael J. Amirian, Kushan Radadia, Hadley Narins, Kelly A. Healy, Scott G. Hubosky, Demetrius H. Bagley, Edouard J. Trabulsi, Costas D. Lallas Nov 2014

The Significance Of Functional Renal Obstruction In Predicting Pathologic Stage Of Upper Tract Urothelial Carcinoma., Michael J. Amirian, Kushan Radadia, Hadley Narins, Kelly A. Healy, Scott G. Hubosky, Demetrius H. Bagley, Edouard J. Trabulsi, Costas D. Lallas

Department of Urology Faculty Papers

BACKGROUND AND PURPOSE: Assessing the severity of upper tract urothelial carcinoma (UTUC) has been difficult because of inadequate biopsy specimens. Additional predictive parameters of disease stage would be useful when deciding a treatment plan; it has been suggested that preoperative hydronephrosis can be a surrogate. We examined the relationship between preoperative ipsilateral renal obstruction identified by imaging with final pathologic stage after nephroureterectomy (NU) for UTUC. We then analyzed those patients with ipsilateral renal obstruction and examined if tumor location is associated with an advanced pathologic stage.

METHODS: Patients who underwent NU for UTUC between the years 2001 to 2013 …


Jewish Dermatologists In Nazi Germany., Walter H.C. Burgdorf, Lawrence Charles Parish Nov 2014

Jewish Dermatologists In Nazi Germany., Walter H.C. Burgdorf, Lawrence Charles Parish

Department of Dermatology and Cutaneous Biology Faculty Papers

With the development of medical specialties beginning in the 1860’s, physicians could devote their time to the study of specific organ systems or surgical approaches. Although Jews had been given full rights in the new Germany by 1871, prejudice and other restrictions often precluded hospital and university appointments. Major specialities like internal medicine and surgery were almost closed to Jews, as were obstetrics and gynecology. Dermatology with its heavy emphasis on sexually transmitted diseases evolved into a suitable domain for Jewish physicians almost by default. Even those Jews who converted to Christianity were not spared from discrimination. Paul Gerson Unna …


Sofas And Infant Mortality., Lauren R. Rechtman, Jeffrey D. Colvin, Peter S. Blair, Rachel Y. Moon Nov 2014

Sofas And Infant Mortality., Lauren R. Rechtman, Jeffrey D. Colvin, Peter S. Blair, Rachel Y. Moon

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Sleeping on sofas increases the risk of sudden infant death syndrome and other sleep-related deaths. We sought to describe factors associated with infant deaths on sofas.

METHODS: We analyzed data for infant deaths on sofas from 24 states in 2004 to 2012 in the National Center for the Review and Prevention of Child Deaths Case Reporting System database. Demographic and environmental data for deaths on sofas were compared with data for sleep-related infant deaths in other locations, using bivariate and multivariable, multinomial logistic regression analyses.

RESULTS: A total of 1024 deaths on sofas made up 12.9% of sleep-related infant …


Role Of A Genetic Variant On The 15q25.1 Lung Cancer Susceptibility Locus In Smoking-Associated Nasopharyngeal Carcinoma, Xuemei Ji, Weidong Zhang, Jiang Gui, Xia Fan, Weiwei Zhang, Yafang Li, Guangyu An, Dakai Zhu, Qiang Hu Oct 2014

Role Of A Genetic Variant On The 15q25.1 Lung Cancer Susceptibility Locus In Smoking-Associated Nasopharyngeal Carcinoma, Xuemei Ji, Weidong Zhang, Jiang Gui, Xia Fan, Weiwei Zhang, Yafang Li, Guangyu An, Dakai Zhu, Qiang Hu

Dartmouth Scholarship

Background: The 15q25.1 lung cancer susceptibility locus, containing CHRNA5, could modify lung cancer susceptibility and multiple smoking related phenotypes. However, no studies have investigated the association between CHRNA5 rs3841324, which has been proven to have the highest association with CHRNA5 mRNA expression, and the risk of other smoking-associated cancers, except lung cancer. In the current study we examined the association between rs3841324 and susceptibility to smoking-associated nasopharyngeal carcinoma (NPC).

Methods: In this case-control study we genotyped the CHRNA5 rs3841324 polymorphism with 400 NPC cases and 491 healthy controls who were Han Chinese and frequency-matched by age (±5 years), gender, and …


Blood Levels Of S-100 Calcium-Binding Protein B, High-Sensitivity C-Reactive Protein, And Interleukin-6 For Changes In Depressive Symptom Severity After Coronary Artery Bypass Grafting: Prospective Cohort Nested Within A Randomized, Controlled Trial, Daniel M. Pearlman, Jeremiah R. R. Brown, Todd A. Mackenzie, Felix Hernandez, Souhel Najjar Oct 2014

Blood Levels Of S-100 Calcium-Binding Protein B, High-Sensitivity C-Reactive Protein, And Interleukin-6 For Changes In Depressive Symptom Severity After Coronary Artery Bypass Grafting: Prospective Cohort Nested Within A Randomized, Controlled Trial, Daniel M. Pearlman, Jeremiah R. R. Brown, Todd A. Mackenzie, Felix Hernandez, Souhel Najjar

Dartmouth Scholarship

Background: Cross-sectional and retrospective studies have associated major depressive disorder with glial activation and injury as well as blood–brain barrier disruption, but these associations have not been assessed prospectively. Here, we aimed to determine the relationship between changes in depressive symptom severity and in blood levels of S-100 calcium- binding protein B (S-100B), high-sensitivity C-reactive protein, and interleukin-6 following an inflammatory challenge.

Methods: Fifty unselected participants were recruited from a randomized, controlled trial comparing coronary artery bypass grafting procedures performed with versus without cardiopulmonary bypass for the risk of neurocognitive decline. Depressive symptom severity was measured at baseline, discharge, and …


Visualization-Aided Classification Ensembles Discriminate Lung Adenocarcinoma And Squamous Cell Carcinoma Samples Using Their Gene Expression Profiles, Ao Zhang, Chi Wang, Shiji Wang, Liang Li, Zhongmin Liu, Suyan Tian Oct 2014

Visualization-Aided Classification Ensembles Discriminate Lung Adenocarcinoma And Squamous Cell Carcinoma Samples Using Their Gene Expression Profiles, Ao Zhang, Chi Wang, Shiji Wang, Liang Li, Zhongmin Liu, Suyan Tian

Markey Cancer Center Faculty Publications

INTRODUCTION: The widespread application of microarray experiments to cancer research is astounding including lung cancer, one of the most common fatal human tumors. Among non-small cell lung carcinoma (NSCLC), there are two major histological types of NSCLC, adenocarcinoma (AC) and squamous cell carcinoma (SCC).

RESULTS: In this paper, we proposed to integrate a visualization method called Radial Coordinate Visualization (Radviz) with a suitable classifier, aiming at discriminating two NSCLC subtypes using patients' gene expression profiles. Our analyses on simulated data and a real microarray dataset show that combining with a classification method, Radviz may play a role in …


Calcium Supplementation Increases Blood Creatinine Concentration In A Randomized Controlled Trial, Elizabeth L. L. Barry, Leila A. A. Mott, Michal L. L. Melamed, Judith R. Rees, Anastasia Ivanova, Robert S. Sandler, Dennis J. Ahnen, Robert S. Bresalier, Robert W. Summers, Roberd M. Bostick, John A. Baron Oct 2014

Calcium Supplementation Increases Blood Creatinine Concentration In A Randomized Controlled Trial, Elizabeth L. L. Barry, Leila A. A. Mott, Michal L. L. Melamed, Judith R. Rees, Anastasia Ivanova, Robert S. Sandler, Dennis J. Ahnen, Robert S. Bresalier, Robert W. Summers, Roberd M. Bostick, John A. Baron

Dartmouth Scholarship

Background: Calcium supplements are widely used among older adults for osteoporosis prevention and treatment. However, their effect on creatinine levels and kidney function has not been well studied.

Methods: We investigated the effect of calcium supplementation on blood creatinine concentration in a randomized controlled trial of colorectal adenoma chemoprevention conducted between 2004–2013 at 11 clinical centers in the United States. Healthy participants (N=1,675) aged 45–75 with a history of colorectal adenoma were assigned to daily supplementation with calcium (1200 mg, as carbonate), vitamin D3 (1000 IU), both, or placebo for three or five years. Changes in blood creatinine and total …