Digital Commons Network^™

Low Doses Of Memantine Disrupt Memory In Adult Rats, Catherine Creeley, David Wozniak, Joanne Labruyere, George Taylor, John Olney

Psychology Faculty Works

Memantine, a drug recently approved for treatment of Alzheimer’s disease, has been characterized as a unique NMDA antagonist that confers protection against excitotoxic neurodegeneration without the serious side effects that other NMDA antagonists are known to cause. In the present study, we determined what dose of memantine is required to protect the adult rat brain against an NMDA receptor-mediated excitotoxic process and then tested that dose and a range of lower doses to determine whether the drug in this dose range is associated with significant side effects. Consistent with previous research, we found that memantine confers a neuroprotective effect beginning …

Cardiac-Specific Elevations In Thyroid Hormone Enhance Contractility And Prevent Pressure Overload-Induced Cardiac Dysfunction, Maria G. Trivieri, Gavin Y. Oudit, Rajan Sah, Benoit-Giles Kerfant, Hui Sun, Anthony O. Gramolini, Yan Pan, Alan D. Wickenden, Walburga Croteau

Dartmouth Scholarship

Thyroid hormone (TH) is critical for cardiac development and heart function. In heart disease, TH metabolism is abnormal, and many biochemical and functional alterations mirror hypothyroidism. Although TH therapy has been advocated for treating heart disease, a clear benefit of TH has yet to be established, possibly because of peripheral actions of TH. To assess the potential efficacy of TH in treating heart disease, type 2 deiodinase (D2), which converts the prohormone thyroxine to active triiodothyronine (T3), was expressed transiently in mouse hearts by using the tetracycline transactivator system. Increased cardiac D2 activity led to elevated cardiac T3 levels and …

Immunization Update, Karl M. Hess, Jeffery A. Goad

Pharmacy Faculty Articles and Research

"Immunization represents a very effective primary prevention strategy to curb the rate of vaccine preventable diseases...Pharmacists can play a leading role in vaccination by serving as an advocate, facilitator, and active immunizer. As an advocate, pharmacists provide vaccine education while motivating people to get immunized. As a facilitator, pharmacy’s can host other groups, such as the visiting nurses association, to come into the pharmacy and vaccinate. As an active immunizer, however, pharmacists serve their greatest role by giving immunizations to adolescents and adults."

Median Survival Time Of Patients After Transcatheter Chemo-Embolization For Hepatocellular Carcinoma, Zeeshan Haider, Haq Ul, Khalid Munir, M Uzair Usman, Muhammad Azeemuddin

Department of Radiology

Objective: To determine the effect on survival after transarterial chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma (HCC).Design: Longitudinal cohort study.PLACE AND DURATION OF STUDY: Radiology Department, The Aga Khan University Hospital, Stadium Road, Karachi, from December 1997 to September 2005.PATIENTS AND Methods: Patients undergoing TACE procedure for HCC were prospectively followed. Fortythree patients were enrolled from December 1997 to March 2003 in the study and subjected to chemoembolization therapy. Eight out of 43 patients were excluded from the study, who lost to follow-up. All the patients were followed till their death. Median and mean survival were calculated.Results: The median …

The Effect Of An Acute Bout Of Aerobic Exercise On Arterial Stiffness And Wave Reflection In Patients With Coronary Artery Disease, Alyssa L. Borell, Cristin A. Davis

Inquiry Journal 2006

No abstract provided.

The Diagnostic Yield Of Various Tests For Helicobacter Pylori Infection In Patients On Acid Reducing Drugs, Javed Yakoob, Wasim Jafri, Z Abbas, Shahab Abid, Muhammad Islam, Saeed Hamid, Syed H Shah

Section of Gastroenterology

No abstract provided.

Comparison Of Og1rf And An Isogenic Fsrb Deletion Mutant By Transcriptional Analysis: The Fsr System Of Enterococcus Faecalis Is More Than The Activator Of Gelatinase And Serine Protease, Agathe Bourgogne, Susan G Hilsenbeck, Gary M Dunny, Barbara E Murray

Faculty, Staff and Student Publications

The FsrABC system of Enterococcus faecalis controls the expression of gelatinase and a serine protease via a quorum-sensing mechanism, and recent studies suggest that the Fsr system may also regulate other genes important for virulence. To investigate the possibility that Fsr influences the expression of additional genes, we used transcriptional profiling, with microarrays based on the E. faecalis strain V583 sequence, to compare the E. faecalis strain OG1RF with its isogenic mutant, TX5266, an fsrB deletion mutant. We found that the presence of an intact fsrB influences expression of numerous genes throughout the growth phases tested, namely, late log to …

Effects Of Sapk/Jnk Inhibitors On Preimplantation Mouse Embryo Development Are Influenced Greatly By The Amount Of Stress Induced By The Media, Yufen Xie, E. E. Puscheck, D. A. Rappolee

Department of Obstetrics and Gynecology Research Publications

Stress-activated protein kinase/c-Jun kinase (SAPK/JNK) is thought to be necessary for preimplantation embryonic development (Maekawa et al., 2005). However, media increases SAPK/JNK phosphorylation and these levels negatively correlate with embryonic development (Wang et al., 2005). Culture-induced stress could confuse analysis of the role of SAPK in development. In this study, we tested how SAPK/JNK inhibitors influence embryonic development in optimal and non-optimal media and define the contribution of cell survival and proliferation to the embryonic response to these media. SAPK/JNK inhibitors retard embryonic development in suboptimal Ham’s F10, but improve development in optimal potassium (K+) simplex optimized media (KSOM) +AA. …

Cationic Amino Acid Transport Across The Blood-Brain Barrier Is Mediated Exclusively By System Y+, Robyn L. O'Kane, Juan R. Viña, Ian Simpson, Rosa Zaragozá, Ashwini Mokashi, Richard A. Hawkins

Publications and Research

Cationic amino acid (CAA) transport is brought about by two families of proteins that are found in various tissues: Cat (CAA transporter), referred to as system y+, and Bat [broad-scope amino acid (AA) transporter], which comprises systems b0,+, B0,+, and y+L. CAA traverse the blood-brain barrier (BBB), but experiments done in vivo have only been able to examine the BBB from the luminal (blood-facing) side. In the present study, plasma membranes isolated from bovine brain microvessels were used to identify and characterize the CAA transporter(s) on both sides of the BBB. From these studies, it was concluded that system y+ …

Hepatic And Renal Cytochrome P450 Gene Regulation During Citrobacter Rodentium Infection In Wild-Type And Toll-Like Receptor 4 Mutant Mice, Terrilyn A Richardson, Melanie Sherman, Leposava Antonovic, Sean S Kardar, Henry W Strobel, Daniel Kalman, Edward T Morgan

Faculty, Staff and Student Publications

Citrobacter rodentium is the rodent equivalent of human enteropathogenic Escherichia coli infection. This study investigated regulation of hepatic and renal cytochrome P450 (P450) mRNAs, hepatic P450 proteins, cytokines, and acute phase proteins during C. rodentium infection. Female C3H/HeOuJ (HeOu) and C3H/HeJ (HeJ) mice [which lack functional toll-like receptor 4 (TLR4)] were infected with C. rodentium by oral gavage and sacrificed 6 days later. Hepatic CYP4A10 and 4A14 mRNAs were decreased in HeOu mice (

Loss Of Sparc-Mediated Vegfr-1 Suppression After Injury Reveals A Novel Antiangiogenic Activity Of Vegf-A, Miho Nozaki, Eiji Sakurai, Brian J. Raisler, Judit Z. Baffi, Jassir Witta, Yuichiro Ogura, Rolf A. Brekken, E Helene Sage, Balamurali K. Ambati, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Publications

VEGF-A promotes angiogenesis in many tissues. Here we report that choroidal neovascularization (CNV) incited by injury was increased by excess VEGF-A before injury but was suppressed by VEGF-A after injury. This unorthodox antiangiogenic effect was mediated via VEGFR-1 activation and VEGFR-2 deactivation, the latter via Src homology domain 2-containing (SH2-containing) tyrosine phosphatase-1 (SHP-1). The VEGFR-1-specific ligand placental growth factor-1 (PlGF-1), but not VEGF-E, which selectively binds VEGFR-2, mimicked these responses. Excess VEGF-A increased CNV before injury because VEGFR-1 activation was silenced by secreted protein, acidic and rich in cysteine (SPARC). The transient decline of SPARC after injury revealed a temporal …

First Report Of Ophthalmomyaisis Externa In Pakistan, Azam Ali, Agha Hassan Feroze, Paul Ferrar, Asad Abbas, Mohammad Asim Beg

Section of Ophthalmology

Two individuals presented to the Aga Khan University Opthalmology service with foreign-body sensation, pain and redness in one of their eyes. Slit-lamp biomicroscopy revealed tiny larvae crawling around the conjunctival sac. They were mechanically removed under topical anaesthesia and preserved for light microscopy and photography. Comprehensive liaison was established with the Australian Centre for International Agriculture Research for identification of these larvae. Their morphology characterized them as members of fruit-fly, Oestridae family. At least one of them was positively identified as first instar larva of Oestrus ovis. This report describes the first instance of such infections in Southern Pakistan, as …

Keeping Their Options Open: Acute Versus Persistent Infections, S. Furukawa, S. L. Kuchma, G. A. O'Toole

Dartmouth Scholarship

No abstract provided.

Treponema Denticola In Disseminating Endodontic Infections, F. Foschi, Jacques Izard, H. Sasaki, V. Sambri, C. Prati, R. Müller, P. Stashenko

Department of Food Science and Technology: Faculty Publications

Treponema denticola is a consensus periodontal pathogen that has recently been associated with endodontic pathology. In this study, the effect of mono-infection of the dental pulp with T. denticola and with polymicrobial “red-complex” organisms (RC) (Porphyromonas gingivalis, Tannerella forsythia, and T. denticola) in inducing disseminating infections in wild-type (WT) and severe-combined-immunodeficiency (SCID) mice was analyzed. After 21 days, a high incidence (5/10) of orofacial abscesses was observed in SCID mice mono-infected with T. denticola, whereas abscesses were rare in SCID mice infected with the red-complex organisms or in wild-type mice. Splenomegaly was …

Do Cd1-Restricted T Cells Contribute To Antibody-Mediated Immunity Against Mycobacterium Tuberculosis?, Mark L. Lang, Aharona Glatman-Freedman

Dartmouth Scholarship

No abstract provided.

Na+/K+ -Atpase Regulates Tight Junction Formation And Function During Mouse Preimplantation Development., Michelle I Violette, Pavneesh Madan, Andrew J Watson

Obstetrics & Gynaecology Publications

Research applied to the early embryo is required to effectively treat human infertility and to understand the primary mechanisms controlling development to the blastocyst stage. The present study investigated whether the Na(+)/K(+)-ATPase regulates tight junction formation and function during blastocyst formation. To investigate this hypothesis, three experimental series were conducted. The first experiments defined the optimal dose and treatment time intervals for ouabain (a potent and specific inhibitor of the Na(+)/K(+)-ATPase) treatment. The results demonstrated that mouse embryos maintained a normal development to the blastocyst stage following a 6-h ouabain treatment. The second experiments investigated the effects of ouabain treatment …

Physiological Effects On Demography: A Long‐Term Experimental Study Of Testosterone’S Effects On Fitness, W. Reed, M. Clark, P. Parker, S. Raouf, N. Arguedas, D. Monk, E. Snajdr, V. Nolan, E. Ketterson

Biology Department Faculty Works

Understanding physiological and behavioral mechanisms underlying the diversity of observed life‐history strategies is challenging because of difficulties in obtaining long‐term measures of fitness and in relating fitness to these mechanisms. We evaluated effects of experimentally elevated testosterone on male fitness in a population of dark‐eyed juncos studied over nine breeding seasons using a demographic modeling approach. Elevated levels of testosterone decreased survival rates but increased success of producing extra‐pair offspring. Higher overall fitness for testosterone‐treated males was unexpected and led us to consider indirect effects of testosterone on offspring and females. Nest success was similar for testosterone‐treated and control males, …

The Impact Of An Hematocrit Of 20% During Normothermic Cardiopulmonary Bypass For Elective Low Risk Coronary Artery Bypass Graft Surgery On Oxygen Delivery And Clinical Outcome – A Randomized Controlled Study [Isrctn35655335], Christian Von Heymann, Michael Sander, Achim Foer, Anja Heinemann, Bruce Spiess, Jan Braun, Michael Krämer, Joachim Grosse, Pascal Dohmen, Simon Dushe, Jürgen Halle, Wolfgang F. Konertz, Klaus-Dieter Warnecke, Claudia Spies

Anesthesiology Publications

Introduction

Cardiopulmonary bypass (CPB) induces hemodilutional anemia, which frequently requires the transfusion of blood products. The objective of this study was to evaluate oxygen delivery and consumption and clinical outcome in low risk patients who were allocated to an hematocrit (Hct) of 20% versus 25% during normothermic CPB for elective coronary artery bypass graft (CABG) surgery.

Methods

This study was a prospective, randomized and controlled trial. Patients were subjected to normothermic CPB (35 to 36°C) and were observed until discharge from the intensive care unit (ICU). Outcome measures were calculated whole body oxygen delivery, oxygen consumption and clinical outcome. A …

The Reckless Pursuit Of Dominion: A Situational Analysis Of The Nba And Diminishing Player Autonomy, Michael Mccann

Law Faculty Scholarship

This Article examines required genetic testing of NBA players from a situational vantage point, integrating socio-psychological, legal, and ethical analyses. The core argument may be expressed as follows: required genetic testing of NBA players appears consistent with a broader and largely deleterious agenda by the NBA to control players. Since implementation of the rookie wage scale in 1995 through the recent imposition of a paternalistic player dress code, the NBA has increasingly usurped player autonomy. The NBA's capacity to do so largely rests in its adroit manipulation of the situational influences that influence fans and media. For instance, because of …

2005 Cancer Care Annual Report, Children's Mercy Hospital

Cancer Center Annual Reports

Annual report of cancer care and oncology services at the Children's Mercy Hospital, Kansas City MO, a pediatric medical center, with a focus on neuroblastoma.

Differences In Mnemonic Processing By Neurons In The Human Hippocampus And Parahippocampal Regions, Indre Viskontas, B. J. Knowlton, P. N. Steinmetz, I. Fried

Psychology

Different structures within the medial-temporal lobe likely make distinct contributions to declarative memory. In particular, several current psychological and computational models of memory predict that the hippocampus and parahippocampal regions play different roles in the formation and retrieval of declarative memories [e.g., Norman, K. A., & O'Reilly, R. C. Modeling hippocampal and neocortical contributions to recognition memory: A complementary-learning systems approach. Psychological Review, 110, 611-646, 2003]. Here, we examined the neuronal firing patterns in these two regions during recognition memory. Recording directly from neurons in humans, we find that cells in both regions respond to novel stimuli with an increase …

Children's Mercy Hospital Annual Report 2005, Children's Mercy Hospital

Children's Mercy Annual Reports

Annual report for The Children's Mercy Hospital in Kansas City MO, a pediatric medical center.

Effect Of Changes In Contractility On The Index Of Myocardial Performance In The Dysfunctional Left Ventricle, Steven J. Lavine

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

The index of myocardial performance has prognostic power in patients with cardiomyopathy and following myocardial infarction. As the index of myocardial performance has been shown to be preload and afterload dependent, the effect of altering contractility on IMP and its components with left ventricular dysfunction has been incompletely delineated.

Methods

Chronic left ventricular dysfunction was induced in 10 canines using coronary microsphere embolization. Each dog was instrumented and imaged with 2D echo and Doppler. At the same atrially paced rate, contractility was increased with a dobutamine infusion and then following 4 weeks of oral digoxin.

Results

With chronic …

Genistein Inhibits Radiation-Induced Activation Of Nf-Κb In Prostate Cancer Cells Promoting Apoptosis And G2/M Cell Cycle Arrest, Julian J. Raffoul, Yu Wang, Omer Kucuk, Jeffrey D. Forman, Fazlul H. Sarkar, Gilda G. Hillman

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

New cancer therapeutic strategies must be investigated that enhance prostate cancer treatment while minimizing associated toxicities. We have previously shown that genistein, the major isoflavone found in soy, enhanced prostate cancer radiotherapy in vitro and in vivo. In this study, we investigated the cellular and molecular interaction between genistein and radiation using PC-3 human prostate cancer cells.

Methods

Tumor cell survival and progression was determined by clonogenic analysis, flow cytometry, EMSA analysis of NF-κB, and western blot analysis of cyclin B1, p21^WAF1/Cip1, and cleaved PARP protein.

Results

Genistein combined with radiation caused greater inhibition in PC-3 …

Arterial Blood Pressure Monitoring In Overweight Critically Ill Patients: Invasive Or Noninvasive?, Ali Araghi, Joseph J. Bander, Jorge A. Guzman

Wayne State University Associated BioMed Central Scholarship

Abstract

Introduction

Blood pressure measurements frequently guide management in critical care. Direct readings, commonly from a major artery, are considered to be the gold standard. Because arterial cannulation is associated with risks, alternative noninvasive blood pressure (NIBP) measurements are routinely used. However, the accuracy of NIBP determinations in overweight patients in the outpatient setting is variable, and little is known about critically ill patients. This prospective, observational study was performed to compare direct intra-arterial blood pressure (IABP) with NIBP measurements obtained using auscultatory and oscillometric methods in overweight patients admitted to our medical intensive care unit.

Method

Adult critically ill …

Characterization Of Pancreatic Lesions From Mt-Tgfα, Ela-Myc And Mt-Tgfα/Ela-Myc Single And Double Transgenic Mice, Dezhong Liao, Yong Wang, Jiusheng Wu, Nazmi Adsay, David Grignon, Fayyaz Khanani, Fazlul H. Sarkar

Wayne State University Associated BioMed Central Scholarship

Abstract

In order to identify good animal models for investigating therapeutic and preventive strategies for pancreatic cancer, we analyzed pancreatic lesions from several transgenic models and made a series of novel findings. Female MT-tgfα mice of the MT100 line developed pancreatic proliferation, acinar-ductal metaplasia, multilocular cystic neoplasms, ductal adenocarcinomas and prominent fibrosis, while the lesions in males were less severe. MT-tgfα-ES transgenic lines of both sexes developed slowly progressing lesions that were similar to what was seen in MT100 males. In both MT100 and MT-tgfα-ES lines, TGFα transgene was expressed mainly in proliferating ductal cells. Ela-myc transgenic mice with a …

Incidence Of Post Myocardial Infarction Left Ventricular Thrombus Formation In The Era Of Primary Percutaneous Intervention And Glycoprotein Iib/Iiia Inhibitors. A Prospective Observational Study, Arshad Rehan, Manpreet Kanwar, Howard Rosman, Sujood Ahmed, Arshad Ali, Julius Gardin, Gerald Cohen

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Before the widespread use of primary percutaneous coronary intervention (PCI) and glycoprotein IIb/IIIa inhibitors (GP IIb/IIIa) left ventricular (LV) thrombus formation had been reported to complicate up to 20% of acute myocardial infarctions (AMI). The incidence of LV thrombus formation with these treatment modalities is not well known.

Methods

92 consecutive patients with ST-elevation AMI treated with PCI and GP IIb/IIIa inhibitors underwent 2-D echocardiograms, with and without echo contrast agent, within 24–72 hours.

Results

Only 4/92 (4.3%) had an LV thrombus, representing a significantly lower incidence than that reported in the pre-PCI era. Use of contrast agents …

Peroxisomal Proliferator Activated Receptor-Γ Deficiency In A Canadian Kindred With Familial Partial Lipodystrophy Type 3 (Fpld3), Gordon A. Francis, Gang Li, Robin Casey, Jian Wang, Henian Cao, Todd Leff, Robert A. Hegele

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Familial partial lipodystrophy (Dunnigan) type 3 (FPLD3, Mendelian Inheritance in Man [MIM] 604367) results from heterozygous mutations in PPARG encoding peroxisomal proliferator-activated receptor-γ. Both dominant-negative and haploinsufficiency mechanisms have been suggested for this condition.

Methods

We present a Canadian FPLD3 kindred with an affected mother who had loss of fat on arms and legs, but no increase in facial, neck, suprascapular or abdominal fat. She had profound insulin resistance, diabetes, severe hypertriglyceridemia and relapsing pancreatitis, while her pre-pubescent daughter had normal fat distribution but elevated plasma triglycerides and C-peptide and depressed high-density lipoprotein cholesterol.

Results

The mother and …

Increased Therapeutic Potential Of An Experimental Anti-Mitotic Inhibitor Sb715992 By Genistein In Pc-3 Human Prostate Cancer Cell Line, David A. Davis, Sarah H. Sarkar, Maha Hussain, Yiwei Li, Fazlul H. Sarkar

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Kinesin spindle proteins (KSP) are motor proteins that play an essential role in mitotic spindle formation. HsEg5, a KSP, is responsible for the formation of the bipolar spindle, which is critical for proper cell division during mitosis. The function of HsEg5 provides a novel target for the manipulation of the cell cycle and the induction of apoptosis. SB715992, an experimental KSP inhibitor, has been shown to perturb bipolar spindle formation, thus making it an excellent candidate for anti-cancer agent. Our major objective was a) to investigate the cell growth inhibitory effects of SB715992 on PC-3 human prostate cancer …

Production Of Il-16 Correlates With Cd4+ Th1 Inflammation And Phosphorylation Of Axonal Cytoskeleton In Multiple Sclerosis Lesions, Dusanka S. Skundric, Juan Cai, William W. Cruikshank, Djordje Gveric

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Multiple sclerosis (MS) is a central nervous system-specific autoimmune, demyelinating and neurodegenerative disease. Infiltration of lesions by autoaggressive, myelin-specific CD4+Th1 cells correlates with clinical manifestations of disease. The cytokine IL-16 is a CD4+ T cell-specific chemoattractant that is biased towards CD4+ Th1 cells. IL-16 precursor is constitutively expressed in lymphocytes and during CD4+ T cell activation; active caspase-3 cleaves and releases C-terminal bioactive IL-16. Previously, we used an animal model of MS to demonstrate an important role for IL-16 in regulation of autoimmune inflammation and subsequent axonal damage. This role of IL-16 in MS is largely unexplored. Here …