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The Limits Of Constructivism: Can Rawls Condemn Female Genital Mutilation?, Andrew Koppelman
The Limits Of Constructivism: Can Rawls Condemn Female Genital Mutilation?, Andrew Koppelman
Faculty Working Papers
The strategy for coping with value pluralism that Rawls has proposed is to permit political decisions, at least with respect to basic rights, to depend only on those goods that can be inferred from the bare requirements of respectful relations between persons. His account offers such a parsimonious conception of the good that it cannot cognize some atrocities. I focus on one extreme human rights case: the practice of female genital mutilation (FGM), which, it is well established, violates basic human rights. Doubtless Rawls was appalled by the practice. Yet his theory cannot generate a basis for condemning it. A …
Ouabain Stimulates A Na+/K+-Atpase-Mediated Sfk-Activated Signalling Pathway That Regulates Tight Junction Function In The Mouse Blastocyst., Holly Giannatselis, Michele Calder, Andrew J Watson
Ouabain Stimulates A Na+/K+-Atpase-Mediated Sfk-Activated Signalling Pathway That Regulates Tight Junction Function In The Mouse Blastocyst., Holly Giannatselis, Michele Calder, Andrew J Watson
Obstetrics & Gynaecology Publications
The Na(+)/K(+)-ATPase plays a pivotal role during preimplantation development; it establishes a trans-epithelial ionic gradient that facilitates the formation of the fluid-filled blastocyst cavity, crucial for implantation and successful pregnancy. The Na(+)/K(+)-ATPase is also implicated in regulating tight junctions and cardiotonic steroid (CTS)-induced signal transduction via SRC. We investigated the expression of SRC family kinase (SFK) members, Src and Yes, during preimplantation development and determined whether SFK activity is required for blastocyst formation. Embryos were collected following super-ovulation of CD1 or MF1 female mice. RT-PCR was used to detect SFK mRNAs encoding Src and Yes throughout preimplantation development. SRC and …
Β-Lactams Interfering With Pbp1 Induce Panton-Valentine Leukocidin Expression By Triggering Sara And Rot Global Regulators Of Staphylococcus Aureus, Oana Dumitrescu, Priya Choudhury, Sandrine Boisset, Cedric Badiou, Michele Bes, Yvonne Benito, Christiane Wolz, Francois Vandenesch, Jerome Etienne, Ambrose L. Cheung
Β-Lactams Interfering With Pbp1 Induce Panton-Valentine Leukocidin Expression By Triggering Sara And Rot Global Regulators Of Staphylococcus Aureus, Oana Dumitrescu, Priya Choudhury, Sandrine Boisset, Cedric Badiou, Michele Bes, Yvonne Benito, Christiane Wolz, Francois Vandenesch, Jerome Etienne, Ambrose L. Cheung
Dartmouth Scholarship
Previous articles reported that beta-lactam antibiotics increase the expression of Staphylococcus aureus Panton-Valentine leukocidin (PVL) by activating its transcription. We investigated the mechanisms underlying the inductor effect of beta-lactams on PVL expression by determining targets and regulatory pathways possibly implicated in this process. We measured PVL production in the presence of oxacillin (nonselective), imipenem (penicillin-binding protein 1 [PBP1] selective), cefotaxime (PBP2 s
The Hypoxia-Adenosine Link During Myocardial Ischemia—Reperfusion Injury, Diana Panesso, Maria C Montealegre, Sandra Rincón, Maria F Mojica, Louis B Rice, Kavindra V Singh, Barbara E Murray, Cesar A Arias
The Hypoxia-Adenosine Link During Myocardial Ischemia—Reperfusion Injury, Diana Panesso, Maria C Montealegre, Sandra Rincón, Maria F Mojica, Louis B Rice, Kavindra V Singh, Barbara E Murray, Cesar A Arias
Faculty, Staff and Student Publications
BACKGROUND: Plasmids containing hylEfm (pHylEfm) were previously shown to increase gastrointestinal colonization and lethality of Enterococcus faecium in experimental peritonitis. The hylEfm gene, predicting a glycosyl hydrolase, has been considered as a virulence determinant of hospital-associated E. faecium, although its direct contribution to virulence has not been investigated. Here, we constructed mutants of the hylEfm-region and we evaluated their effect on virulence using a murine peritonitis model.
RESULTS: Five mutants of the hylEfm-region of pHylEfmTX16 from the sequenced endocarditis strain (TX16 [DO]) were obtained using an adaptation of the PheS* system and were evaluated in a commensal strain TX1330RF to …
The Cardiac Atlas Project--An Imaging Database For Computational Modeling And Statistical Atlases Of The Heart, Carissa G. Fonseca, Michael Backhaus, David A. Bluemke, Randall D. Britten, Jae Do Chung, Brett R. Cowan, Alan H. Kadish
The Cardiac Atlas Project--An Imaging Database For Computational Modeling And Statistical Atlases Of The Heart, Carissa G. Fonseca, Michael Backhaus, David A. Bluemke, Randall D. Britten, Jae Do Chung, Brett R. Cowan, Alan H. Kadish
Office of the President Publications and Research
MOTIVATION: Integrative mathematical and statistical models of cardiac anatomy and physiology can play a vital role in understanding cardiac disease phenotype and planning therapeutic strategies. However, the accuracy and predictive power of such models is dependent upon the breadth and depth of noninvasive imaging datasets. The Cardiac Atlas Project (CAP) has established a large-scale database of cardiac imaging examinations and associated clinical data in order to develop a shareable, web-accessible, structural and functional atlas of the normal and pathological heart for clinical, research and educational purposes. A goal of CAP is to facilitate collaborative statistical analysis of regional heart shape …
Animal-Assisted Therapy: An Adjunctive Intervention For Reducing Depression And Anxiety In Female College Students With Physical Disabilities And Guidelines For Implementation Into Psychotherapy Practice And Research, Erin Nicole Armour
Browse all Theses and Dissertations
The existing literature has indicated that women with physical disabilities are at greater risk for depression and anxiety compared to men with similar limitations and their able-bodied counterparts (Nosek & Hughes, 2003). In addition to this, female college students with physical disabilities are at greater risk for attrition than able-bodied female college students (Gmelch, 1998). This dissertation discusses the benefits and criticisms of animal-assisted therapy as an adjunctive intervention for depression and anxiety in this population. It also provides guidelines for implementing it into psychotherapy practice and research.
Rosuvastatin Therapy Does Not Affect Serum Mmp-13 Or Timp-1 Levels In Hypercholesterolemic Patients, Cihan Cevik, Kenneth Nugent, Gary Meyerrose, Mohammad Otahbachi, Cemil Izgi, Mark Lyte, R David Fish
Rosuvastatin Therapy Does Not Affect Serum Mmp-13 Or Timp-1 Levels In Hypercholesterolemic Patients, Cihan Cevik, Kenneth Nugent, Gary Meyerrose, Mohammad Otahbachi, Cemil Izgi, Mark Lyte, R David Fish
The Texas Heart Institute Journal
Matrix metalloproteinases degrade the collagen content of atherosclerotic plaque and reduce plaque stability. In tissue sections of atherosclerotic plaque, the expression of matrix metalloproteinases is increased. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) decrease the tissue expression of matrix metalloproteinases-1, -2, -3, and -9 in atheromatous plaque by attenuating the inflammatory process that leads to increased expression. However, it is not known whether statins decrease levels of matrix metalloproteinase-13—an enzyme crucial to the initiation of collagen degradation—as part of their plaque-stabilizing effect.
We prospectively examined the effect of statin therapy on serum levels of matrix metalloproteinase-13, tissue inhibitor of metalloproteinase-1, and …
Association Of Retinoic Acid Receptor Genes With Meningomyelocele, Phong X Tran, Kit Sing Au, Alanna C Morrison, Jack M Fletcher, Kathryn K Ostermaier, Gayle H Tyerman, Hope Northrup
Association Of Retinoic Acid Receptor Genes With Meningomyelocele, Phong X Tran, Kit Sing Au, Alanna C Morrison, Jack M Fletcher, Kathryn K Ostermaier, Gayle H Tyerman, Hope Northrup
Faculty, Staff and Student Publications
BACKGROUND: Neural tube defects (NTDs) occur in as many as 0.5-2 per 1000 live births in the United States. One of the most common and severe neural tube defects is meningomyelocele (MM) resulting from failed closure of the caudal end of the neural tube. MM has been induced by retinoic acid teratogenicity in rodent models. We hypothesized that genetic variants influencing retinoic acid (RA) induction via retinoic acid receptors (RARs) may be associated with risk for MM.
METHODS: We analyzed 47 single nucleotide polymorphisms (SNPs) that span across the three retinoic acid receptor genes using the SNPlex genotyping platform. Our …
Innate And Cytokine-Driven Signals, Rather Than Microbial Antigens, Dominate In Natural Killer T Cell Activation During Microbial Infection, Manfred Brigl, Raju V.V. Tatituri, Gerald F.M. Watts, Veemal Bhowruth, Elizabeth A. Leadbetter, Nathaniel Barton, Nadia R. Cohen, Fong-Fu Hsu, Gurdyal S. Besra, Michael B. Brenner
Innate And Cytokine-Driven Signals, Rather Than Microbial Antigens, Dominate In Natural Killer T Cell Activation During Microbial Infection, Manfred Brigl, Raju V.V. Tatituri, Gerald F.M. Watts, Veemal Bhowruth, Elizabeth A. Leadbetter, Nathaniel Barton, Nadia R. Cohen, Fong-Fu Hsu, Gurdyal S. Besra, Michael B. Brenner
Open Access Publications
Invariant natural killer T cells (iNKT cells) are critical for host defense against a variety of microbial pathogens. However, the central question of how iNKT cells are activated by microbes has not been fully explained. The example of adaptive MHC-restricted T cells, studies using synthetic pharmacological α-galactosylceramides, and the recent discovery of microbial iNKT cell ligands have all suggested that recognition of foreign lipid antigens is the main driver for iNKT cell activation during infection. However, when we compared the role of microbial antigens versus innate cytokine-driven mechanisms, we found that iNKT cell interferon-γ production after in vitro stimulation or …
Tdp-43 Potentiates Alpha-Synuclein Toxicity To Dopaminergic Neurons In Transgenic Mice., Tian Tian, Cao Huang, Jianbin Tong, Ming Yang, Hongxia Zhou, Xugang Xia
Tdp-43 Potentiates Alpha-Synuclein Toxicity To Dopaminergic Neurons In Transgenic Mice., Tian Tian, Cao Huang, Jianbin Tong, Ming Yang, Hongxia Zhou, Xugang Xia
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
TDP-43 and α-synuclein are two disease proteins involved in a wide range of neurodegenerative diseases. While TDP-43 proteinopathy is considered a pathologic hallmark of sporadic amyotrophic lateral sclerosis and frontotemporal lobe degeneration, α-synuclein is a major component of Lewy body characteristic of Parkinson's disease. Intriguingly, TDP-43 proteinopathy also coexists with Lewy body and with synucleinopathy in certain disease conditions. Here we reported the effects of TDP-43 on α-synuclein neurotoxicity in transgenic mice. Overexpression of mutant TDP-43 (M337V substitution) in mice caused early death in transgenic founders, but overexpression of normal TDP-43 only induced a moderate loss of cortical neurons in …
The Incidence Of Type-1 Diabetes In Nod Mice Is Modulated By Restricted Flora Not Germ-Free Conditions., Cecile King, Nora Sarvetnick
The Incidence Of Type-1 Diabetes In Nod Mice Is Modulated By Restricted Flora Not Germ-Free Conditions., Cecile King, Nora Sarvetnick
Journal Articles: Regenerative Medicine
In the NOD mouse, the incidence of type-1 diabetes is thought to be influenced by the degree of cleanliness of the mouse colony. Studies collectively demonstrate that exposure to bacterial antigen or infection in the neonatal period prevents diabetes [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], supporting the notion that immunostimulation can benefit the maturation of the postnatal immune system [11]. A widely accepted extrapolation from this data has been the notion that NOD mice maintained under germ-free conditions have an increased incidence of diabetes. However, evidence supporting this influential concept is surprisingly limited [12]. In this …
A Dosing Study Of Bone Marrow Mononuclear Cells For Transendocardial Injection In A Pig Model Of Chronic Ischemic Heart Disease, Guilherme V Silva, Marlos R Fernandes, Cristiano O Cardoso, Ricardo R Sanz, Edie M Oliveira, Pilar Jimenez-Quevedo, Javier Lopez, Franca S Angeli, Yi Zheng, James T Willerson, Emerson C Perin
A Dosing Study Of Bone Marrow Mononuclear Cells For Transendocardial Injection In A Pig Model Of Chronic Ischemic Heart Disease, Guilherme V Silva, Marlos R Fernandes, Cristiano O Cardoso, Ricardo R Sanz, Edie M Oliveira, Pilar Jimenez-Quevedo, Javier Lopez, Franca S Angeli, Yi Zheng, James T Willerson, Emerson C Perin
The Texas Heart Institute Journal
We studied the effect of the dose of bone marrow mononuclear cells, delivered via transendocardial injection, upon capillary density and fibrosis in pigs with chronic ischemic heart disease.
Pigs (n = 16) that had undergone ameroid constrictor placement (left circumflex coronary artery) to induce chronic ischemia were divided equally into 4 groups on the basis of bone marrow mononuclear cell dose: control (saline injection) and 50, 100, or 200 × 106 bone marrow mononuclear cells. Thirty days after ameroid placement, each pig received 13 transendocardial NOGA-guided injections. An implantable loop recorder monitored possible arrhythmias caused by cell transplantation. Thirty days …
Paclitaxel Induces Thrombomodulin Downregulation In Human Aortic Endothelial Cells, Huang-Joe Wang, Te-Ling Lu, Haimei Huang, Huey-Chun Huang
Paclitaxel Induces Thrombomodulin Downregulation In Human Aortic Endothelial Cells, Huang-Joe Wang, Te-Ling Lu, Haimei Huang, Huey-Chun Huang
The Texas Heart Institute Journal
Patients with paclitaxel-eluting stents are at risk of developing stent thrombosis upon premature discontinuation of dual antiplatelet therapy. In this study, we set out to clarify whether paclitaxel can modulate thrombomodulin expression in human aortic endothelial cells. Human aortic endothelial cells were stimulated with paclitaxel. Methoxyphenyl tetrazolium inner salt cell viability assay, Western blot analysis, real-time polymerase chain reaction, and immunohistochemical assay were performed. In human aortic endothelial cells, paclitaxel (10(-5) to 10(-9) mol/L) treatment for 13 hours caused significant cytotoxicity at drug concentrations greater than 10(-7) mol/L. Paclitaxel (10(-5) to 10(-9) mol/L) treatment for 5 hours downregulated thrombomodulin expression …
Referrals To A Regional Allergy Clinic - An Eleven Year Audit., Ray B. Jones, Paul Hewson, Edward R. Kaminski
Referrals To A Regional Allergy Clinic - An Eleven Year Audit., Ray B. Jones, Paul Hewson, Edward R. Kaminski
School of Nursing and Midwifery
BACKGROUND: Allergy is a serious and apparently increasing public health problem yet relatively little is known about the types of allergy seen in routine tertiary practice, including their spatial distribution, co-occurrence or referral patterns. This study reviewed referrals over an eleven year period to a regional allergy clinic that had a well defined geographical boundary. For those patients confirmed as having an allergy we explored: (i) differences over time and by demographics, (ii) types of allergy, (iii) co-occurrence, and (iv) spatial distributions. METHODS: Data were extracted from consultant letters to GPs, from September 1998 to September 2009, for patients confirmed …
Golgi Cells Operate As State-Specific Temporal Filters At The Input Stage Of The Cerebellar Cortex, Shane A. Heine, Stephen M. Highstein, Pablo M. Blazquez
Golgi Cells Operate As State-Specific Temporal Filters At The Input Stage Of The Cerebellar Cortex, Shane A. Heine, Stephen M. Highstein, Pablo M. Blazquez
Open Access Publications
Cerebellar processing of incoming information begins at the synapse between mossy fibers and granule cells, a synapse that is strongly controlled through Golgi cell inhibition. Thus, Golgi cells are uniquely positioned to control the flow of information into the cerebellar cortex and understanding their responses during behavior is essential to understanding cerebellar function. Here we show, for the first time, that Golgi cells express a unique oculomotor-related signal that can be used to provide state- and time-specific filtering of granule cell activity. We used newly established criteria to identify the unique electrophysiological signature of Golgi cells and recorded these neurons …
C-Jun Inhibits Mammary Apoptosis In Vivo., Sanjay Katiyar, Mathew C Casimiro, Luis Dettin, Xiaoming Ju, Erwin F Wagner, Hirokazu Tanaka, Richard Pestell
C-Jun Inhibits Mammary Apoptosis In Vivo., Sanjay Katiyar, Mathew C Casimiro, Luis Dettin, Xiaoming Ju, Erwin F Wagner, Hirokazu Tanaka, Richard Pestell
Department of Cancer Biology Faculty Papers
c-jun, which is overexpressed in a number of human cancers encodes a critical component of the AP-1 complex. c-jun has been shown to either induce or inhibit cellular apoptosis. Germ line deletion of both c-jun alleles is embryonically lethal. To determine the role of the endogenous c-jun gene in apoptosis, we performed mammary epithelial cell-targeted somatic deletion using floxed c-jun (c-jun(f/f)) conditional knockout mice. Laser capture microdissection demonstrated endogenous c-jun inhibits expression of apoptosis inducing genes and reactive oxygen species (ROS)-reducing genes (MnSOD, catalase). ROS have been implicated in apoptosis and undergo enzymatic elimination via MnSOD and CuZnSOD with further …
A New Species Of Cyclobulura (Nematoda: Subuluridae) From Zaedyus Pichiy And Chaetophractus Vellerosus (Xenarthra: Dasypodidae) In Argentina, Graciela T Navone, María C Ezquiaga, Juliana Notarnicola, F Agustín Jiménez-Ruiz
A New Species Of Cyclobulura (Nematoda: Subuluridae) From Zaedyus Pichiy And Chaetophractus Vellerosus (Xenarthra: Dasypodidae) In Argentina, Graciela T Navone, María C Ezquiaga, Juliana Notarnicola, F Agustín Jiménez-Ruiz
Publications
Cyclobulura superinae n. sp. collected from Zaedyus pichiy and Chaetophractus vellerosus is herein described as the second species in Cyclobulura Quentin, 1977, and the first subulurid in armadillos. The species is unique in the spur-like structures present at the tip of both spicules, yet they conform to the description of Cyclobulura in the structure of the buccal parts. Specimens of the new species show longer chordal lobes and more conspicuous radial lobes and are smaller than specimens of C. lainsoni. In addition, males of C. superinae exhibit a spur-like process in the distal end of the spicules and a shorter …
Voices Raised, Issue 30, University Of Dayton. Women's Center
Voices Raised, Issue 30, University Of Dayton. Women's Center
Women’s Center Newsletter
Included in this issue: Sisterhood of the Traveling Scarf; Dr. Corvino Speaks on Homosexuality; Center for Social Concern Offers Break-out Trips; UD Shows Continues Dedication to Women’s Athletics; The A Team; There’s no (bent) grass growing under these sisters feet; The Importance of Taking Time for Yourself; Home for the Holidays; Unique Nativity Scenes; Thanks to those who make UD “run like butter”.
Calcium Regulates Vesicle Replenishment At The Cone Ribbon Synapse., Norbert Babai, Theodore M. Bartoletti, Wallace B. Thoreson
Calcium Regulates Vesicle Replenishment At The Cone Ribbon Synapse., Norbert Babai, Theodore M. Bartoletti, Wallace B. Thoreson
Journal Articles: Ophthalmology
Cones release glutamate-filled vesicles continuously in darkness, and changing illumination modulates this release. Because sustained release in darkness is governed by vesicle replenishment rates, we analyzed how cone membrane potential regulates replenishment. Synaptic release from cones was measured by recording postsynaptic currents in Ambystoma tigrinum horizontal or OFF bipolar cells evoked by depolarization of simultaneously voltage-clamped cones. We measured replenishment after attaining a steady state between vesicle release and replenishment using trains of test pulses. Increasing Ca(2+) currents (I(Ca)) by changing the test step from -30 to -10 mV increased replenishment. Lengthening -30 mV test pulses to match the Ca(2+) …
Biparental Mucus Feeding: A Unique Example Of Parental Care In An Amazonian Cichlid., Jonathan Buckley, Richard J. Maunder, Andrew Foey, Janet Pearce, Adalberto L. Val, Katherine A. Sloman
Biparental Mucus Feeding: A Unique Example Of Parental Care In An Amazonian Cichlid., Jonathan Buckley, Richard J. Maunder, Andrew Foey, Janet Pearce, Adalberto L. Val, Katherine A. Sloman
School of Biomedical Sciences
Vertebrates display a wide variety of parental care behaviours, including the guarding of offspring pre and post nutritional independence as well as the direct provision of nutrients during the early development period. The Amazonian cichlid Symphysodon spp. (discus fish) is unusual among fish species, in that both parents provide offspring with mucus secretions to feed from after hatching. This extensive provision of care, which can last up to a month, imposes a physiological demand on both parents and gives rise to conflict between the parent and offspring. Here, we investigated the relationship between parents and offspring during a breeding cycle, …
The Endogenous Soluble Vegf Receptor-2 Isoform Suppresses Lymph Node Metastasis In A Mouse Immunocompetent Mammary Cancer Model, Masa-Aki Shibata, Jayakrishna Ambati, Eiko Shibata, Romulo J. C. Albuquerque, Junji Morimoto, Yuko Ito, Yoshinori Otsuki
The Endogenous Soluble Vegf Receptor-2 Isoform Suppresses Lymph Node Metastasis In A Mouse Immunocompetent Mammary Cancer Model, Masa-Aki Shibata, Jayakrishna Ambati, Eiko Shibata, Romulo J. C. Albuquerque, Junji Morimoto, Yuko Ito, Yoshinori Otsuki
Ophthalmology and Visual Science Faculty Publications
BACKGROUND: Cancer metastasis contributes significantly to cancer mortality and is facilitated by lymphangiogenesis and angiogenesis. A new splicing variant, endogenous soluble vascular endothelial growth factor receptor-2 (esVEGFR-2) that we recently identified is an endogenous selective inhibitor of lymphangiogenesis. To evaluate the antimetastatic potential of esVEGFR-2, gene therapy with vector expressing esVEGFR-2 (pesVEGFR-2) or endostatin (pEndo) as a positive control was conducted on murine metastatic mammary cancer.
METHODS: Syngeneic inoculated metastatic mammary cancers received direct intratumoral injection of pesVEGFR-2, pEndo or pVec as control, once a week for six weeks. In vivo gene electrotransfer was performed on the tumors after each …
Chronic Spontaneous Activity Generated In The Somata Of Primary Nociceptors Is Associated With Pain-Related Behavior After Spinal Cord Injury, Supinder S Bedi, Qing Yang, Robyn J Crook, Junhui Du, Zizhen Wu, Harvey M Fishman, Raymond J Grill, Susan M Carlton, Edgar T Walters
Chronic Spontaneous Activity Generated In The Somata Of Primary Nociceptors Is Associated With Pain-Related Behavior After Spinal Cord Injury, Supinder S Bedi, Qing Yang, Robyn J Crook, Junhui Du, Zizhen Wu, Harvey M Fishman, Raymond J Grill, Susan M Carlton, Edgar T Walters
Faculty, Staff and Student Publications
Mechanisms underlying chronic pain that develops after spinal cord injury (SCI) are incompletely understood. Most research on SCI pain mechanisms has focused on neuronal alterations within pain pathways at spinal and supraspinal levels associated with inflammation and glial activation. These events might also impact central processes of primary sensory neurons, triggering in nociceptors a hyperexcitable state and spontaneous activity (SA) that drive behavioral hypersensitivity and pain. SCI can sensitize peripheral fibers of nociceptors and promote peripheral SA, but whether these effects are driven by extrinsic alterations in surrounding tissue or are intrinsic to the nociceptor, and whether similar SA occurs …
Simvastatin Enhances Immune Responses To Aβ Vaccination And Attenuates Vaccination-Induced Behavioral Alterations, Jinghong Kou, Hong-Duck Kim, Jingji Jin, Dongfeng Cao, Ling Li, Robert Lalonde, Ken-Ichiro Fukuchi
Simvastatin Enhances Immune Responses To Aβ Vaccination And Attenuates Vaccination-Induced Behavioral Alterations, Jinghong Kou, Hong-Duck Kim, Jingji Jin, Dongfeng Cao, Ling Li, Robert Lalonde, Ken-Ichiro Fukuchi
NYMC Faculty Publications
Statins are widely used to lower cholesterol levels by inhibiting cholesterol biosynthesis. Some evidence has indicated that statins might have therapeutic and preventive benefits for Alzheimer's disease (AD). We and others also have shown the beneficial effect of statin treatment in reversing learning and memory deficits in animal models of AD. However, data from clinical trials are inconclusive. We previously documented that the adenovirus vector encoding 11 tandem repeats of Aβ1-6 fused to the receptor-binding domain (Ia) of Pseudomonas exotoxin A, AdPEDI-(Aβ1-6)(11), is effective in inducing an immune response against amyloid-β protein (Aβ) and reducing brain Aβ load in Alzheimer's …
Alterations In Multiple Measures Of White Matter Integrity In Normal Women At High Risk For Alzheimer's Disease, Brian T. Gold, David K. Powell, Anders H. Andersen, Charles D. Smith
Alterations In Multiple Measures Of White Matter Integrity In Normal Women At High Risk For Alzheimer's Disease, Brian T. Gold, David K. Powell, Anders H. Andersen, Charles D. Smith
Neuroscience Faculty Publications
There is evidence that disruption of white matter (WM) microstructure is an early event in the course of Alzheimer's disease (AD). However, the neurobiological bases of WM microstructural declines in presymptomatic AD are unknown. In the present study we address this issue using a multimodal imaging approach to the study of presymptomatic AD. Participants were 37 high-risk (both family history of dementia and one or more APOE4 alleles) women and 20 low-risk (neither family history nor APOE4) women. Groups were matched for age, education, neuropsychological performance, and vascular factors that could affect white matter. Whole-brain analyses of diffusion tensor imaging …
Research Priorities In Hypertrophic Cardiomyopathy: Report Of A Working Group Of The National Heart, Lung, And Blood Institute., Thomas Force, Robert O Bonow, Steven R Houser, R John Solaro, Ray E Hershberger, Bishow Adhikari, Mark E Anderson, Robin Boineau, Barry J Byrne, Thomas P Cappola, Raghu Kalluri, Martin M Lewinter, Martin S Maron, Jeffery D Molkentin, Steve R Ommen, Michael Regnier, W H Wilson Tang, Rong Tian, Marvin A Konstam, Barry J Maron, Christine E Seidman
Research Priorities In Hypertrophic Cardiomyopathy: Report Of A Working Group Of The National Heart, Lung, And Blood Institute., Thomas Force, Robert O Bonow, Steven R Houser, R John Solaro, Ray E Hershberger, Bishow Adhikari, Mark E Anderson, Robin Boineau, Barry J Byrne, Thomas P Cappola, Raghu Kalluri, Martin M Lewinter, Martin S Maron, Jeffery D Molkentin, Steve R Ommen, Michael Regnier, W H Wilson Tang, Rong Tian, Marvin A Konstam, Barry J Maron, Christine E Seidman
Center for Translational Medicine Faculty Papers
Hypertrophic cardiomyopathy (HCM) is a myocardial disorder characterized by left ventricular (LV) hypertrophy without dilatation and without apparent cause (ie, it occurs in the absence of severe hypertension, aortic stenosis, or other cardiac or systemic diseases that might cause LV hypertrophy). Numerous excellent reviews and consensus documents provide a wealth of additional background.1–8 HCM is the leading cause of sudden death in young people and leads to significant disability in survivors. It is caused by mutations in genes that encode components of the sarcomere. Cardiomyocyte and cardiac hypertrophy, myocyte disarray, interstitial and replacement fibrosis, and dysplastic intramyocardial arterioles characterize the …
Deficient Liver Biosynthesis Of Docosahexaenoic Acid Correlates With Cognitive Impairment In Alzheimer's Disease, Giuseppe Astarita, Kwang-Mook Jung, Nicole C. Berchtold, Vinh Q. Nguyen, Daniel L. Gillen, Elizabeth Head, Carl W. Cotman, Daniele Piomelli
Deficient Liver Biosynthesis Of Docosahexaenoic Acid Correlates With Cognitive Impairment In Alzheimer's Disease, Giuseppe Astarita, Kwang-Mook Jung, Nicole C. Berchtold, Vinh Q. Nguyen, Daniel L. Gillen, Elizabeth Head, Carl W. Cotman, Daniele Piomelli
Sanders-Brown Center on Aging Faculty Publications
Reduced brain levels of docosahexaenoic acid (C22:6n-3), a neurotrophic and neuroprotective fatty acid, may contribute to cognitive decline in Alzheimer's disease. Here, we investigated whether the liver enzyme system that provides docosahexaenoic acid to the brain is dysfunctional in this disease. Docosahexaenoic acid levels were reduced in temporal cortex, mid-frontal cortex and cerebellum of subjects with Alzheimer's disease, compared to control subjects (P = 0.007). Mini Mental State Examination (MMSE) scores positively correlated with docosahexaenoic/α-linolenic ratios in temporal cortex (P = 0.005) and mid-frontal cortex (P = 0.018), but not cerebellum. Similarly, liver docosahexaenoic acid content was lower in Alzheimer's …
Quantitative Imaging Reveals Heterogeneous Growth Dynamics And Treatment-Dependent Residual Tumor Distributions In A Three-Dimensional Ovarian Cancer Model, Jonathan P. Celli, Imran Rizvi, Conor L. Evans, Adnan O. Abu-Yousif, Tayyaba Hasan
Quantitative Imaging Reveals Heterogeneous Growth Dynamics And Treatment-Dependent Residual Tumor Distributions In A Three-Dimensional Ovarian Cancer Model, Jonathan P. Celli, Imran Rizvi, Conor L. Evans, Adnan O. Abu-Yousif, Tayyaba Hasan
Dartmouth Scholarship
Three-dimensional tumor models have emerged as valuable in vitro research tools, though the power of such systems as quantitative reporters of tumor growth and treatment response has not been adequately explored. We introduce an approach combining a 3-D model of disseminated ovarian cancer with high-throughput processing of image data for quantification of growth characteristics and cytotoxic response. We developed custom MATLAB routines to analyze longitudinally acquired dark-field microscopy images containing thousands of 3-D nodules. These data reveal a reproducible bimodal log-normal size distribution. Growth behavior is driven by migration and assembly, causing an exponential decay in spatial density concomitant with …
Association Between Chronic Liver And Colon Inflammation During The Development Of Murine Syngeneic Graft-Versus-Host Disease, Jason Anthony Brandon, Jacqueline Perez-Rodriguez, C. Darrell Jennings, Donald A. Cohen, Vishal J. Sindhava, Subbarao Bondada, Alan M. Kaplan, J. Scott Bryson
Association Between Chronic Liver And Colon Inflammation During The Development Of Murine Syngeneic Graft-Versus-Host Disease, Jason Anthony Brandon, Jacqueline Perez-Rodriguez, C. Darrell Jennings, Donald A. Cohen, Vishal J. Sindhava, Subbarao Bondada, Alan M. Kaplan, J. Scott Bryson
Microbiology, Immunology, and Molecular Genetics Faculty Publications
The murine model of cyclosporine A (CsA)-induced syngeneic graft-versus-host disease (SGVHD) is a bone marrow (BM) transplantation model that develops chronic colon inflammation identical to other murine models of CD4+ T cell-mediated colitis. Interestingly, SGVHD animals develop chronic liver lesions that are similar to the early peribiliary inflammatory stages of clinical chronic liver disease, which is frequently associated with inflammatory bowel disease (IBD). Therefore, studies were initiated to investigate the chronic liver inflammation that develops in the SGVHD model. To induce SGVHD, mice were lethally irradiated, reconstituted with syngeneic BM, and treated with CsA. All of the SGVHD animals …
A Case Study In Unethical Transgressive Bioethics: "Letter Of Concern From Bioethicists" About The Prenatal Administration Of Dexamethasone., Laurence B Mccullough, Frank A Chervenak, Robert L Brent, Benjamin Hippen
A Case Study In Unethical Transgressive Bioethics: "Letter Of Concern From Bioethicists" About The Prenatal Administration Of Dexamethasone., Laurence B Mccullough, Frank A Chervenak, Robert L Brent, Benjamin Hippen
Department of Pediatrics Faculty Papers
On February 3, 2010, a "Letter of Concern from Bioethicists," organized by fetaldex.org, was sent to report suspected violations of the ethics of human subjects research in the off-label use of dexamethasone during pregnancy by Dr. Maria New. Copies of this letter were submitted to the FDA Office of Pediatric Therapeutics, the Department of Health and Human Services (DHHS) Office for Human Research Protections, and three universities where Dr. New has held or holds appointments. We provide a critical appraisal of the Letter of Concern and show that it makes false claims, misrepresents scientific publications and websites, fails to meet …
Age-Related Deterioration Of Rod Vision In Mice, Alexander V. Kolesnikov, Jie Fan, Rosalie K. Crouch, Vladimir J. Kefalov
Age-Related Deterioration Of Rod Vision In Mice, Alexander V. Kolesnikov, Jie Fan, Rosalie K. Crouch, Vladimir J. Kefalov
Open Access Publications
Even in healthy individuals, aging leads to deterioration in visual acuity, contrast sensitivity, visual field, and dark adaptation. Little is known about the neural mechanisms that drive the age-related changes of the retina and, more specifically, photoreceptors. According to one hypothesis, the age-related deterioration in rod function is due to the limited availability of 11-cis-retinal for rod pigment formation. To determine how aging affects rod photoreceptors and to test the retinoid-deficiency hypothesis, we compared the morphological and functional properties of rods of adult and aged B6D2F1/J mice. We found that the number of rods and the length of their outer …