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The Cns Role Of Toll-Like Receptor 4 In Innate Neuroimmunity And Painful Neuropathy, Flobert Y. Tanga, Nancy Nutile-Mcmenemy, Joyce A. Deleo

Dartmouth Scholarship

Neuropathic pain remains a prevalent and persistent clinical problem because of our incomplete understanding of its pathogenesis. This study demonstrates for the first time, to our knowledge, a critical role for CNS innate immunity by means of microglial Toll-like receptor 4 (TLR4) in the induction phase of behavioral hypersensitivity in a mouse and rat model of neuropathy. We hypothesized that after L5 nerve transection, CNS neuroimmune activation and subsequent cytokine expression are triggered by the stimulation of microglial membrane-bound TLR4. To test this hypothesis, experiments were undertaken to assess tactile and thermal hypersensitivity in genetically altered (i.e., TLR4 knockout and …

Ocular Surface Epithelia Contain Abcg2-Dependent Side Population Cells Exhibiting Features Associated With Stem Cells., Murat T Budak, Onder S Alpdogan, Mingyuan Zhou, Robert M Lavker, M A Murat Akinci, J Mario Wolosin

Department of Medical Oncology Faculty Papers

When cell populations are incubated with the DNA-binding dye Hoechst 33342 and subjected to flow cytometry analysis for Hoechst 33342 emissions, active efflux of the dye by the ABCG2/BCRP1 transporter causes certain cells to appear as a segregated cohort, known as a side population (SP). Stem cells from several tissues have been shown to possess the SP phenotype. As the lack of specific surface markers has hindered the isolation and subsequent biochemical characterization of epithelial stem cells this study sought to determine the existence of SP cells and expression of ABCG2 in the epithelia of the ocular surface and evaluate …

Effect Of Serum And Cumulus Cell Expansion On Marker Gene Transcripts In Bovine Cumulus-Oocyte Complexes During Maturation In Vitro., Michele D Calder, Anita N Caveney, Marc-Andre Sirard, Andrew J Watson

Obstetrics & Gynaecology Publications

OBJECTIVE: To determine the distribution of transcripts encoding the FSH receptor (FSHr), LH receptor (LHr), connexin 43 (Cx43), cyclooxygenase-2 (COX-2), and prostaglandin E(2) receptors 2 and 3 (EP2 and EP3) within bovine cumulus-oocyte complexes (COCs) and denuded oocytes and investigate the influence of gonadotropins, serum, and cumulus cell expansion on the abundance of transcripts encoding these genes.

DESIGN: Prospective controlled animal study.

SETTING: University research laboratory.

PATIENT(S): Animal models for human studies.

INTERVENTION(S): Cumulus-oocyte complexes were treated in culture with serum and gonadotropin-supplemented media to examine the effects to mRNA transcript levels.

MAIN OUTCOME MEASURE(S): Variation in mRNA transcript levels. …

Bench-To-Bedside Review: Rhabdomyolysis -- An Overview For Clinicians., Ana L Huerta-Alardín, Joseph Varon, Paul E Marik

Jefferson Hospital Staff Papers and Presentations

Rhabdomyolysis ranges from an asymptomatic illness with elevation in the creatine kinase level to a life-threatening condition associated with extreme elevations in creatine kinase, electrolyte imbalances, acute renal failure and disseminated intravascular coagulation. Muscular trauma is the most common cause of rhabdomyolysis. Less common causes include muscle enzyme deficiencies, electrolyte abnormalities, infectious causes, drugs, toxins and endocrinopathies. Weakness, myalgia and tea-colored urine are the main clinical manifestations. The most sensitive laboratory finding of muscle injury is an elevated plasma creatine kinase level. The management of patients with rhabdomyolysis includes early vigorous hydration.

The Effects Of Greater Occipital Nerve Block And Trigger Point Injection On Brush Allodynia And Pain In Migraine, Avi Ashkenazi, William B. Young

Department of Neurology Faculty Papers

Objective: To evaluate the effect of GONB, with or without trigger point injection (TPI), on dynamical mechanical (brush) allodynia (BA) and on head pain in migraine.

Background: Patients with migraine often have cutaneous allodynia, which is related to sensitization of central pain neurons. Greater occipital nerve block (GONB) is an effective treatment for migraine headache, however its effect on cutaneous allodynia in migraine is unknown.

Methods: We studied patients with migraine and BA who were treated with GONB with or without TPI. Demographic data, migraine history and headache features were documented. Allodynia was evaluated using a structured …

Mechanisms Of Cell Death Initiated In Herpes Simplex Virus Thymidine Kinase Expressing Colon Tumor Cells Treated With Ganciclovir And Ucn-01, Christina Elizabeth Ahn

Theses and Dissertations in Biomedical Sciences

Metastatic colon carcinoma is the second leading cause of death from malignancy in the United States, and development of more effective treatments is essential. Heterologous expression of Herpes Simplex Virus Thymidine Kinase (HSVtk) in combination with the prodrug, ganciclovir (GCV), has shown great promise for the genetic therapy of many cancers, but most patients have had only a partial or minimal response to the therapy. After screening a panel of two drug combinations, our laboratory has shown that the combination of GCV and the protein kinase inhibitor UCN-01 (7-hydroxystaurosporine) enhances tumor cell death more effectively than either drug alone. However …

The Antitumor Agent, Arglabin-Dma, Preferentially Induces Apoptosis In Human Colon Tumor Cells, Sung Wook Kwon

Theses and Dissertations in Biomedical Sciences

Arglabin-DMA, an analog of farnesyl pyrophosphate (FPP), reportedly inhibits farnesyltransferase (FTase) directly by competitively blocking the binding of Ras protein and its posttranslational modification, as suggested in previous studies. But, the mechanisms by which Arglabin-DMA inhibits tumor growth in vivo and in vitro are still relatively poorly characterized. To determine the mechanism by which this drug inhibits tumor growth, the effects of Arglabin-DMA in two human colon tumor cell lines (mutant K-ras HCT 116 and wild-type ras HT-29) were explored on cell proliferation, apoptosis, and cell cycle kinetics in vitro. In cell viability studies, we showed that Arglabin-DMA …

James Jarell “Jake” Pickle And Clifford Drummond Oral History Interview, March 15, 2005, James "Jake" Jarrell Pickle, Clifford Drummond, Lesley W. Brunet, Earl Walborg

Interview Sessions

Major Topics Covered:

• Sources of land for MD Anderson Research Park in Smithville and Bastrop, Texas
• Legislators and others instrumental in advocating in the Legislature
• R. Lee Clark’s vision for a research facility; personal motives for locating the facility outside of Houston
• Local and governmental considerations in approving land for a laboratory

Vital Signs, Spring 2005, Boonshoft School Of Medicine

Vital Signs

A twenty-eight page newsletter created by the Boonshoft School of Medicine to document the current affairs of the school. This issue includes a variety of feature articles, alumni and faculty profiles, class notes, and more.

Digest Of The Philadelphia College Of Osteopathic Medicine (Spring 2005), Philadelphia College Of Osteopathic Medicine

Digest

The Spring 2005 issue of the Digest of the Philadelphia College of Osteopathic Medicine includes the following articles:

• Opening Remarks
• PCOM Updates and Kudos
• The Courage to Change Lives
• ALS Research: Surveying the Quality of Devastated Lives
• Class Notes
• In Memoriam
• My Turn
• PCOM Events

Attributional Styles Of Women Who Quit Or Reduce Smoking In The Antepartum, Patricia T. Alpert

Loma Linda University Electronic Theses, Dissertations & Projects

Background: Researchers in the field of smoking have sought to identify variables that predict whether or not pregnant smokers stop or continue to smoke. Most variables examined are demographic in nature and little is known about psychological variables associated with those who quit or reduce smoking while pregnant.

Purpose: To analyze attributional style and locus of control to determine which factors alone, or in combination, are associated with quitting versus reduced smoking among pregnant smokers.

Methodology: Pregnant smokers who quit (n = 66) or reduced their smoking (n = 43) were identified by the nursing staff at a women’s county …

Involvement Of Beta-Chemokines In The Development Of Inflammatory Demyelination., Ileana Banisor, Thomas P Leist, Bernadette Kalman

Department of Neurology Faculty Papers

The importance of beta-chemokines (or CC chemokine ligands - CCL) in the development of inflammatory lesions in the central nervous system of patients with multiple sclerosis and rodents with experimental allergic encephalomyelitis is strongly supported by descriptive studies and experimental models. Our recent genetic scans in families identified haplotypes in the genes of CCL2, CCL3 and CCL11-CCL8-CCL13 which showed association with multiple sclerosis. Complementing the genetic associations, we also detected a distinct regional expression regulation for CCL2, CCL7 and CCL8 in correlation with chronic inflammation in multiple sclerosis brains. These observations are in consensus with previous studies, and add new …

Defective B Cell Responses In The Absence Of Sh2d1a, Massimo Morra, Robert A. Barrington, Ana C. Abadia-Molina, Susumo Okamoto, Aimee Julien, Charles A. Gullo Phd, Anuj Kalsy, Matthew J. Edwards, Gang Chen, Rosanne Spolski, Warren J. Leonard, Brigitte T. Huber, Persephone Borrow, Christine A. Biron A. Biron, Abhay R. Satoskar, Michael C. Carroll, Cox Terhorst

Biochemistry and Microbiology

More than half of patients with X-linked lympho-proliferative disease, which is caused by a defect in the intracellular adapter protein SH2D1A, suffer from an extreme susceptibility to Epstein-Barr virus. One-third of these patients, however, develop dysgammaglobulenemia without an episode of severe mononucleosis. Here we show that in SH2D1A-/- mice, both primary and secondary responses of all Ig subclasses are severely impaired in response to specific antigens. Because germinal centers were absent in SH2D1A-/- mice upon primary immunization, and because SH2D1A was detectable in wt germinal center B cells, we examined whether SH2D1A-/- B cell functions were impaired. Using the adoptive …

Quantitative 1h Magnetic Resonance Spectroscopic Imaging Determines Therapeutic Immunization Efficacy In An Animal Model Of Parkinson's Disease., Michael D. Boska, Travis B. Lewis, Christopher J. Destache, Eric J. Benner, Jay A. Nelson, Mariano Uberti, R. Lee Mosley, Howard Gendelman

Journal Articles: Radiology

Nigrostriatal degeneration, the pathological hallmark of Parkinson's disease (PD), is mirrored by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication. MPTP-treated animals show the common behavioral, motor, and pathological features of human disease. We demonstrated previously that adoptive transfer of Copaxone (Cop-1) immune cells protected the nigrostriatal dopaminergic pathway in MPTP-intoxicated mice. Herein, we evaluated this protection by quantitative proton magnetic resonance spectroscopic imaging (1H MRSI). 1H MRSI performed in MPTP-treated mice demonstrated that N-acetyl aspartate (NAA) was significantly diminished in the substantia nigra pars compacta (SNpc) and striatum, regions most affected in human disease. When the same regions were coregistered with immunohistochemical stains for …

Oncolog, Volume 50, Number 02/03, February/March 2005, David Galloway

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

• Biostatistically Speaking
• Novel Drugs Address Gleevec Resistance
• Obesity: A Weighty Contributor to Cancer
• House Call: When a Friend Has Cancer

Multiple Metabolic Hits Converge On Cd36 As Novel Mediator Of Tubular Epithelial Apoptosis In Diabetic Nephropathy., Katalin Susztak, Emilio Ciccone, Peter Mccue, Kumar Sharma, Erwin P Böttinger

Department of Medicine Faculty Papers

BACKGROUND: Diabetic nephropathy (DNP) is a common complication of type 1 and type 2 diabetes mellitus and the most common cause of kidney failure. While DNP manifests with albuminuria and diabetic glomerulopathy, its progression correlates best with tubular epithelial degeneration (TED) and interstitial fibrosis. However, mechanisms leading to TED in DNP remain poorly understood.

METHODS AND FINDINGS: We found that expression of scavenger receptor CD36 coincided with proximal tubular epithelial cell (PTEC) apoptosis and TED specifically in human DNP. High glucose stimulated cell surface expression of CD36 in PTECs. CD36 expression was necessary and sufficient to mediate PTEC apoptosis induced …

Expression Of Hepatocyte Growth Factor And Its Receptor C-Met, Correlates With Severity Of Pathological Injury In Experimental Alcoholic Liver Disease., El-Nasir Lalani, Richard Poulsom, Gordon Stamp, Franz Fogt, Peter Thomas, Amin A. Nanji

Department of Pathology and Laboratory Medicine

Expression of hepatocyte growth factor (HGF) and its receptor, c-met is up-regulated in various forms of liver injury. This study evaluated the relationship between HGF and c-met expression and pathological changes in experimental alcoholic liver disease. Rats (5 per group) were fed ethanol and a diet containing saturated fat corn oil or fish oil by intragastric infusion. Dextrose isocalorically replaced ethanol in controls. In a second set of experiments, Kupffer cells, endothelial cells and hepatocytes were isolated from rats in each group. Pathological evaluation and analysis of HGF and c-met expression were performed in liver and the different cell types. …

Passive Immunization During Pregnancy For Congenital Cytomegalovirus Infection, Giovanni Nigro, Stuart P. Adler, Renato La Torre, Al M. Best

Pediatrics Publications

BACKGROUND

Currently, there is no effective intervention for a primary cytomegalovirus (CMV) infection during pregnancy.

METHODS

We studied pregnant women with a primary CMV infection. The therapy group comprised women whose amniotic fluid contained either CMV or CMV DNA and who were offered intravenous CMV hyperimmune globulin at a dose of 200 U per kilogram of maternal weight. A prevention group, consisting of women with a recent primary infection before 21 weeks' gestation or who declined amniocentesis, was offered monthly hyperimmune globulin (100 U per kilogram intravenously).

RESULTS

In the therapy group, 31 women received hyperimmune globulin, only 1 (3 …

Prenatal Stress And Stress Physiology Influences Human Fetal And Infant Development, Elyssia Poggi Davis, Calvin J. Hobel, Curt A. Sandman, Laura M. Glynn, Pathik D. Wadhwa

Psychology Faculty Books and Book Chapters

"Prenatal stress has been proposed as a risk factor that may have developmental consequences persisting throughout the lifespan. Exposing rodents to stress during pregnancy has consequences for brain development, stress regulation, learning, emotionality (increased anxiety), and social behavior (increased withdrawal) of the offspring (Weinstock, 2001; Chapillon et al., 2002). Additionally, non-human primates who experience stress during pregnancy have offspring with enhanced behavioral reactivity to stressors later in life (Clarke et al., 1994), lowered levels of motor behavior (Schneider, 1992), compromised neuromotor responses (Schneider and Coe, 1993), irritable temperament (Schneider et al., 1992), and attentional problems (Schneider et …

Effects Of Aging On Pressure-Induced Mapk Activation In The Rat Aorta, Kevin M. Rice

Theses, Dissertations and Capstones

With age, the cardiovascular system experiences substantial alterations in cellular morphology and function. The factors regulating these changes are unknown; however, the mitogen activated protein kinase (MAPK) pathways have emerged as critical components for mediating numerous cellular responses including control of cell growth, differentiation and adaptation. Here we compare the expression, basal activation and the ability of increased pressure to activate the MAPK pathways in adult (6 month old), aged (30 month old) and very aged (36 month old) Fischer 344 x Brown Norway F1 Hybrid rats. Histochemical analysis demonstrated an age-related increase in tunica media thickness of approximately 11% …

Effects Of Tamoxifen On Mitochondrial Nos Activity: Alteration In The Intramitochondrial Ca2+ Homeostasis, Sandeep S. Joshi

Theses, Dissertations and Capstones

Tamoxifen (Tam) is an anticancer drug that induces oxidative stress and apoptosis via mitochondria- and nitric oxide (NO)-dependent pathways. Here, we report that therapeutic concentrations of Tam stimulate the mitochondrial NO synthase (mtNOS) activity of isolated rat liver mitochondria by increasing the intramitochondrial ionized Ca²⁺ concentration ([Ca²⁺]_m). Tam decreases transmembrane potential (∆ψ) due to increased [Ca²⁺]_m that neutralizes the negative charges of the inner mitochondrial membrane. Thus, the present study reports a novel mechanism for the widely used anti- caner drug, Tam.

Thyroid Hormone-Regulated Skeletal Muscle Glut4 Glucose Transporter Trafficking During Fasting In Diet-Induced Obesity And Insulin Resistance, Lucy Soo Yon Jun

Theses Digitization Project

This thesis project will investigate the effects of fasting on the serum levels of two key regulatory hormones, insulin and thyroid hormone (T3) and the effects of these hormones on the trafficking of Glut4 on soleus muscle.

Tgf-Beta1 And Serum Both Stimulate Contraction But Differentially Affect Apoptosis In 3d Collagen Gels, Tetsu Kobayashi, Xiangde Liu, Hui Jung Kim, Tadashi Kohyama, Fu-Qiang Wen, Shinji Abe, Qiuhong Fang, Yun Kui Zhu, John R. Spurzem, Peter Bitterman, Stephen I. Rennard

Journal Articles: Pulmonary & Critical Care Med

Apoptosis of fibroblasts may be key for the removal of cells following repair processes. Contraction of three-dimensional collagen gels is a model of wound healing and remodeling. Here two potent inducers of contraction, TGF-beta1 and fetal calf serum (FCS) were evaluated for their effect on fibroblast apoptosis in contracting collagen gels. Human fetal lung fibroblasts were cultured in floating type I collagen gels, exposed to TGF-beta1 or FCS, and allowed to contract for 5 days. Apoptosis was evaluated using TUNEL and confirmed by DNA content profiling. Both TGF-beta1 and serum significantly augmented collagen gel contraction. TGF-beta1 also increased apoptosis assessed …

Delayed Supramalleolar Flap: An Innovative Technique For Enhanced Viability, Syed Kamran Ahmed, Pervaiz Mehmood Hashmi

Section of Orthopaedic Surgery

Background: Delaying flap rotation for 48 to 72 hours leads to opening of choke anastomotic vessels linking adjacent vascular territories. This mechanism enhances flap circulation. Lateral supramalleolar flap with larger dimensions or vascular variations can potentially have survival problems. The purpose of this study is to assess the outcome of delayed lateral supramalleolar flap.
Methods: This descriptive case series was conducted at Aga Khan University Hospital, Karachi from May 1999 to December 2004. Eight cases of delayed lateral supramalleolar flap were identified through medical records maintained through Health Information Management Systems (HIMS). A detailed questionnaire was developed addressing variables of …

Old Legacies And New Paradigms: Confusing "Research" And "Treatment" And Its Consequences In Responding To Emergent Health Threats, Gail H. Javitt

Journal of Health Care Law and Policy

No abstract provided.

Department Of Radiology-Annual Executive Summary Report-July 1, 2004 To June 30, 2005, Vijay M. Rao M.D.

Department of Radiology Administrative Documents and Reports

88 page Department of Radiology Annual Executive Summary Report, July 1, 2004 to June 30, 2005, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, United States.

A Preliminary Study Of 24-Hour Post-Cesarean Patient Controlled Analgesia: Postoperative Pain Reports And Morphine Requests/Utilization Are Greater In Abstaining Smokers Than Non-Smokers, Alan P. Marco, Mark K. Greenwald, Michael S. Higgins

Anesthesiology Faculty Publications

Previous clinical studies have not examined the relationship between nicotine abstinence and opioid use for postoperative analgesia. This may be important because tobacco smokers are routinely required to abstain from smoking just before and during acute post-surgical recovery. This study investigated IV morphine self-administration [patient controlled analgesia (PCA)], subjective pain/drug effects and other measures during post-operative (elective Cesarean section) recovery.

These preliminary data suggest that a history of nicotine use and/or short-term nicotine abstinence can modulate morphine use and analgesia during post-operative recovery. These procedures provide a model for studying patterns and determinants of analgesic self-administration in medical settings.

Plasma Zinc Concentrations Are Depressed During The Acute Phase Response In Children With Falciparum Malaria, C. Duggan, W.B. Macleod, N.F. Krebs, J.L. Westcott, W.W. Fawzi, Zul Premji, V. Mwanakasale, J.L. Simon, K. Yeboah-Antwi, D.H. Hamer

Pathology, East Africa

Plasma concentrations of some micronutrients are altered in the setting of acute infectious or inflammatory stress. Previous studies have provided conflicting evidence concerning the extent and direction of changes in plasma zinc concentrations during the acute phase response. We carried out an observational cohort study in 689 children enrolled in a randomized trial of zinc supplementation during acute falciparum malaria in order to evaluate the relation between plasma zinc concentration and the acute phase response. Plasma zinc was measured by atomic absorption spectrophotometry. On admission, 70% of all subjects had low plasma zinc (<9.2 μmol/L). Multivariate analysis of predictors of admission plasma zinc showed that admission C-reactive protein (CRP), parasite density, and study site were the most important predictors. Predictors of changes in plasma zinc from admission to 72 h included baseline CRP, change in CRP, treatment group, study site, and baseline zinc concentration. In children with acute malaria infection, baseline plasma zinc concentrations were very low and were inversely correlated with CRP (r = -0.24, P < 0.0001) and the degree of parasitemia (r = -0.19, P < 0.0001). Even when CRP and time were taken into account, zinc supplementation increased plasma zinc concentration from admission to 72 h. When available, plasma zinc concentrations should be interpreted with concurrent measures of the acute phase response such as CRP. In children whose age, diet, and/or nutritional status place them at risk of zinc deficiency, those with low plasma zinc levels should be supplemented with oral zinc and followed for clinical and/or biochemical response. © 2005 American Society for Nutritional Sciences.

Clioquinol And Pyrrolidine Dithiocarbamate Complex With Copper To Form Proteasome Inhibitors And Apoptosis Inducers In Human Breast Cancer Cells, Kenyon G. Daniel, Di Chen, Shirley Orlu, Qiuzhi Cui, Fred R. Miller, Q Ping Dou

Wayne State University Associated BioMed Central Scholarship

Abstract

Introduction

A physiological feature of many tumor tissues and cells is the tendency to accumulate high concentrations of copper. While the precise role of copper in tumors is cryptic, copper, but not other trace metals, is required for angiogenesis. We have recently reported that organic copper-containing compounds, including 8-hydroxyquinoline-copper(II) and 5,7-dichloro-8-hydroxyquinoline-copper(II), comprise a novel class of proteasome inhibitors and tumor cell apoptosis inducers. In the current study, we investigate whether clioquinol (CQ), an analog of 8-hydroxyquinoline and an Alzheimer's disease drug, and pyrrolidine dithiocarbamate (PDTC), a known copper-binding compound and antioxidant, can interact with copper to form cancer-specific proteasome …

Oncolog, Volume 50, Number 01, January 2005, Rachel Williams, Dawn Chalaire, Caren E. Blinka, Angelina Esparza, Allen W. Burton Md

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

• New Perspectives on Brain Metastasis
• Out of the Darkroom
• Equity and Health
• House Call: Blood and Platelet Donors Give Life
• DiaLog: Cancer Pain Control in the New Millennium, by Allen W. Burton, MD, Section Chief, Cancer Pain Management Department of Anesthesiology and Pain Medicine