Medical Specialties Commons^™

Method Of Inhibiting Alu Rna And Therapeutic Uses Thereof, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Patents

The presently-disclosed subject matter includes methods of identifying an Alu RNA inhibitor, and methods and compo sitions for inhibiting Alu RNA. Methods and compositions can be used for the treatment of geographic atrophy and other conditions of interest.

Similar Promotion Of Abeta1-42 Fibrillogenesis By Native Apolipoprotein E Epsilon3 And Epsilon4 Isoforms, David Sweeney, Ralph Martins, Harry Levine, Jonathan D. Smith, Sam Gandy

Sanders-Brown Center on Aging Faculty Publications

The apolipoprotein E epsilon4 allele contributes to the genetic susceptibility underlying a large proportion (~40-60%) of typical, sporadic Alzheimer disease. Apolipoprotein E deficient mice made transgenic for human apolipoprotein E epsilon4 accumulate excess cerebral amyloid when compared to similarly prepared mice expressing human apolipoprotein E epsilon3. Therefore, it is important to search for relevant interactions(s) between apolipoprotein E epsilon4 and Abeta in order to clarify the biological role for apolipoprotein E epsilon4 in Alzheimer disease. Using a thioflavine T (ThT)-based assay, we have investigated the effects of native human apolipoprotein E isoforms on the kinetics of Abeta fibrillogenesis. No obvious …

Il-5 Links Adaptive And Natural Immunity In Reducing Atherosclerotic Disease, Alan Daugherty, Debra L. Rateri, Victoria L. King

Gill Heart & Vascular Institute Faculty Publications

Oxidized LDL induces changes in several facets of the immune system, although the relationships between these facets and their contributions to atherogenesis have yet to be fully elucidated. A report in this issue of the JCI provides a novel demonstration of the adaptive immune system influencing the production of natural antibodies. The results demonstrate that injection of malondialdehyde-modified LDL promotes a Th2 response that in turn increases the titers of the natural antibody T15/EO6, which recognizes the oxidized phospholipid POVPC. Atherosclerotic lesion size in LDL receptor–deficient mice is reduced as a consequence of the increase in natural antibody titers, and …

Long-Term Evaluation Of The Use Of The Transdermal Contraceptive Patch In Adolescents, Stephanie Logsdon, Jessica Richards, Hatim A. Omar

Pediatrics Faculty Publications

The transdermal contraceptive patch, Ortho Evra™, was approved in December 2001 and released on the market in June 2002. In this study, we reviewed clinical data of young women who started the patch between June 2002 and December 2003 in the adolescent medicine clinic at a university-based outpatient center. A total of 62 patients started the patch in that period and two of them were lost to follow-up. Mean age of patients was 17.9 years and mean length of use was 10 cycles. Only 10 patients (16.7%) discontinued use. Reasons for discontinuation were moderate to severe skin irritation (3 patients, …

Clinical Profiles, Occurrence, And Management Of Adolescent Patients With Hair-An Syndrome, Hatim A. Omar, Stephanie Logsdon, Jessica Richards

Pediatrics Faculty Publications

The syndrome of hyperandrogenism, insulin resistance, and acanthosis nigricans (HAIR-AN) is a subphenotype of the polycystic ovary syndrome. It is one of the most common causes of menstrual problems, hyperandrogenic symptoms, and insulin resistance among young women. Review of clinical data in an outpatient adolescent clinic showed that of the 1,002 young women (ages 10-21 years) attending the clinic over a 2-year period, 50 (5%) were diagnosed with HAIR-AN syndrome. Mean age of the patients was 15.5, initial mean weight at diagnosis was 94.5 kg, and the mean BMI was 33.33 kg/m2. Patients were treated with a weight-stabilization and -reduction …

Methods To Impair Hematologic Cancer Progenitor Cells And Compounds Related Thereto, Craig Jordan

Internal Medicine Faculty Patents

Primitive or progenitor hematologic cancer cells have been implicated in the early stages and development of leukemia and malignant lymphoproliferative disorders, including acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML) and chronic lymphoid leukemia (CLL). Interleukin-3 receptor alpha chain (IL-3Rα or CD123) is strongly expressed on progenitor hematologic cancer cells, but is virtually undetectable on normal bone marrow cells. The present invention provides methods of impairing progenitor hematologic cancer (e.g., leukemia and lymphomic) cells by selectively targeting cells expressing CD123. These methods are useful in the detection and treatment of leukemias and malignant lymphoproliferative disorders. Also provided are compounds useful …

Co-Regulation Of Expression Of Phase Ii Metabolizing Enzymes And Multidrug Resistance-Associated Protein 2, Viviana A. Catania, Enrique J. Sánchez Pozzi, Marcelo G. Luquita, María L. Ruiz, Silvina S. M. Villanueva, Brett Jones, Aldo D. Mottino

Toxicology and Cancer Biology Faculty Publications

Treatment of experimental animals with prototypical enzyme inducers represents a useful tool to characterize the role of different isozymes in drug metabolism and to improve our knowledge on factors regulating their synthesis at the transcriptional level. The effect of model enzyme inducers on phase II (conjugating) enzyme families, including UDP-glucuronosyltransferase’s and glutathione-S-transferase’s, has been well characterized in rodent liver. More recently, the effect of inducers on the expression of canalicular multidrug resistance-associated protein 2 (Mrp2) has been focused upon. The identification of a number of conjugated drugs as Mrp2 substrates suggests that both the conjugation and transport systems act coordinately …

Molecular Functionalization Of Carbon Nanotubes And Use As Substrates For Neuronal Growth, Mark P. Mattson, Robert C. Haddon, Apparao M. Rao

Sanders-Brown Center on Aging Faculty Patents

A cell and substrate system and nerve regeneration implant are disclosed including a carbon nanotube and a neuron growing on the carbon nanotube. Both unfunctionalized carbon nanotubes and carbon nanotubes functionalized with a neuronal growth promoting agent may be utilized in the invention. A method is also disclosed for promoting neuronal growth.

Flexible Recording/High Energy Electrode Catheter With Anchor For Ablation Of Atrial Flutter By Radio Frequency Energy, Chien-Suu Kuo, John G. Gurley

Internal Medicine Faculty Patents

An electrode catheter is provided having a predetermined flexibility throughout the entire length or at least at the contact portion, such as the electrode region, to allow for the molding of the contact portion such that it conforms to the shape of the heart at a preselected desired target area, such as the isthmus between the inlet of inferior vena cava and posterior tricuspid annulus. The catheter also includes a guiding sheath that is preferably semirigid and may be pre-shaped with at least one bend or angulation to assist in molding to ensure that the electrode region overlies the desired …

Vegf164-Mediated Inflammation Is Required For Pathological, But Not Physiological, Ischemia-Induced Retinal Neovascularization, Susumu Ishida, Tomohiko Usui, Kenji Yamashiro, Yuichi Kaji, Shiro Amano, Yuichiro Ogura, Tetsuo Hida, Yoshihisa Oguchi, Jayakrishna Ambati, Joan W. Miller, Evangelos S. Gragoudas, Yin-Shan Ng, Patricia A. D'Amore, David T. Shima, Anthony P. Adamis

Ophthalmology and Visual Science Faculty Publications

Hypoxia-induced VEGF governs both physiological retinal vascular development and pathological retinal neovascularization. In the current paper, the mechanisms of physiological and pathological neovascularization are compared and contrasted. During pathological neovascularization, both the absolute and relative expression levels for VEGF₁₆₄ increased to a greater degree than during physiological neovascularization. Furthermore, extensive leukocyte adhesion was observed at the leading edge of pathological, but not physiological, neovascularization. When a VEGF₁₆₄-specific neutralizing aptamer was administered, it potently suppressed the leukocyte adhesion and pathological neovascularization, whereas it had little or no effect on physiological neovascularization. In parallel experiments, genetically altered VEGF_{164 …}

Psychosocial Stress And Cervical Neoplasia Risk, Ann L. Coker, Sharon M. Bond, Margaret M. Madeleine, Kathryn J. Luchok, Lucia Pirisi

CRVAW Faculty Journal Articles

OBJECTIVE: We assessed the association between psychosocial stress and preinvasive cervical neoplasia development controlling for HR-HPV infection.

METHODS: This case-control study enrolled low-income women receiving family planning services at health department clinics. There were 59 cases with biopsy confirmed HSIL and 163 with low-grade SIL and 160 controls with normal cervical cytology. A modified SLE scale was used to measure stressful events and the perceived impact of the event in the prior 5 years. Unconditional logistic regression was used to assess SIL risk and stressful events scores and by subscales.

RESULTS: After adjusting for age, HR-HPV infection, and lifetime number …

Adolescent Violence Prevention: A Case Presentation, Hatim A. Omar, Joan Griffith

Pediatrics Faculty Publications

Violence in adolescence has seen an increase since the 1990s with dramatic statistics on violent death and risk behaviors. School violence has been focused upon by a huge media coverage of especially violent cases that could have had some endemic consequences worldwide. We present a case of a 14 year old white male with change in school behavior, strategies for the case investigation, its results, and long term prevention. Other research has shown that preventive measures during pregnancy, infancy and childhood can prevent adolescent and adult delinquency.

Hdl-Associated Estradiol Stimulates Endothelial No Synthase And Vasodilation In An Sr-Bi–Dependent Manner, Ming Gong, Melinda E. Wilson, Thomas Kelly, Wen Su, James Dressman, Jeanie Kincer, Sergey V. Matveev, Ling Guo, Theresa Guerin, Xiang-An Li, Weifei Zhu, Annette M. Uittenbogaard, Eric J. Smart

Pediatrics Faculty Publications

Cardiovascular diseases remain the leading cause of death in the United States. Two factors associated with a decreased risk of developing cardiovascular disease are elevated HDL levels and sex — specifically, a decreased risk is found in premenopausal women. HDL and estrogen stimulate eNOS and the production of nitric oxide, which has numerous protective effects in the vascular system including vasodilation, antiadhesion, and anti-inflammatory effects. We tested the hypothesis that HDL binds to its receptor, scavenger receptor class B type I (SR-BI), and delivers estrogen to eNOS, thereby stimulating the enzyme. HDL isolated from women stimulated eNOS, whereas HDL isolated …

Hiv Protease Inhibitors Promote Atherosclerotic Lesion Formation Independent Of Dyslipidemia By Increasing Cd36-Dependent Cholesteryl Ester Accumulation In Macrophages, James Dressman, Jeanie Kincer, Sergey V. Matveev, Ling Guo, Richard N. Greenberg, Theresa Guerin, David Meade, Xiang-An Li, Weifei Zhu, Annette M. Uittenbogaard, Melinda E. Wilson, Eric J. Smart

Physiology Faculty Publications

Protease inhibitors decrease the viral load in HIV patients, however the patients develop hypertriglyceridemia, hypercholesterolemia, and atherosclerosis. It has been assumed that protease inhibitor–dependent increases in atherosclerosis are secondary to the dyslipidemia. Incubation of THP-1 cells or human PBMCs with protease inhibitors caused upregulation of CD36 and the accumulation of cholesteryl esters. The use of CD36-blocking antibodies, a CD36 morpholino, and monocytes isolated from CD36 null mice demonstrated that protease inhibitor–induced increases in cholesteryl esters were dependent on CD36 upregulation. These data led to the hypothesis that protease inhibitors induce foam cell formation and consequently atherosclerosis by upregulating CD36 and …

Educating Adolescents About Puberty: What Are We Missing?, Hatim A. Omar, Darby H. Mcelderry, Rana M. Zakharia

Pediatrics Faculty Publications

Adolescents undergo significant physical and cognitive changes during their pubertal development. These changes contribute to and impact their future development. Educating adolescents at an early age about their expected development decreases the possible anxiety associated with this period of life and also helps adolescents make better choices in regards to their sexuality. In order to assess the degree of education regarding pubertal development and sexuality, we conducted a survey of late adolescents (Median age 19 years) and parents of adolescents. A total of 409 adolescents (237 females, 172 males) and 124 parents completed the survey. 14.4% of teens (36.6% of …

Our Adolescents--Our Future, Hatim A. Omar

Pediatrics Faculty Publications

No abstract provided.

Sex Education In The Schools: What Role Does It Play?, Darby H. Mcelderry, Hatim A. Omar

Pediatrics Faculty Publications

Information regarding pubertal development, sex, pregnancy, and contraception should be provided to children and adolescents in an age-appropriate manner from parents, health care providers, and schools. This article reviews the medical literature on school sex education programs, adolescents' perception of these programs, and the role played by the media, parents, and health care professionals in sexual education of teens.

Parenting Adolescents, Sandra L. D'Angelo, Hatim A. Omar

Pediatrics Faculty Publications

The period of adolescence is often thought to be one of intense stress and turmoil. Yet many parents and teens negotiate this developmental stage without extreme family conflict and without sacrificing close relationships. This review summarizes a portion of the literature on parent-adolescent relationships, focusing on monitoring and control of adolescent behavior and parenting style. Basic principles to emphasize when working with adolescents and parents are also included.

Effectiveness Of Current Therapy Of Bacterial Vaginosis, Petya M Andreeva, Hatim A. Omar

Pediatrics Faculty Publications

The study was conducted in order to evaluate effectiveness of the treatment of bacterial vaginosis (BV) with different therapeutic regimes according to recommendations of the World Health Organization (WHO). During a one-year period (February 2000-February 2001) the Sexually Transmitted Diseases (STD) Center was visited by 482 women aged 14-51. The diagnosis of BV was established by standard methods: Amsel's clinical criteria and Gram stain of vaginal discharge. The first-line treatment was oral Metronidazole 2 g single dose. Second line was Metronidazole 500 mg twice daily orally for 7 days or oral Clindamycin 300 mg twice daily for seven days. BV …

Improved Continuation Rate Of Depot-Medroxyprogesterone Acetate In Adolescent Mothers, Hatim A. Omar, Amy Fowler, Sandy D'Angelo

Pediatrics Faculty Publications

Poor compliance and high discontinuation rates of Depot-Medroxyprogesterone Acetate (DMPA) and other contraceptive methods are major factors in the continuing problem of adolescent pregnancy. In this study we attempted to determine if providing comprehensive health care for teen mothers and their babies would improve continuation rates of DMPA. Patients who started DMPA between 1/1/96 and 1/1/99 were included. Teen mothers and their babies received all their health care in this clinic, supported by State funding. Key elements regarding DMPA in this clinic were continuity of care, phone and mail reminders of appointments, free DMPA for patients without insurance, counseling at …

Retrospective Analysis Of Youth Evaluated For Suicide Attempt Or Suicidal Ideation In An Emergency Room Setting, Julie Hagedorn, Hatim A. Omar

Pediatrics Faculty Publications

Suicide is the third leading cause of death in adolescents and a major contributor to morbidity in this age group. The objective of this study was to look at the demographics, major stressors and factors leading to attempting suicide as well as the methods of attempted suicide in adolescents admitted to two hospitals in a medium size city. Medical records were reviewed of adolescents admitted to two area hospitals for attempted suicide between 7/1/97-12/31/99. Coroner's data on completed suicide were also reviewed. In the study period a total of 287 persons aged 21 years or under were admitted for attempted …

Spatio-Temporal Variation In Activation Intervals During Ventricular Fibrillation, Sachin Anil Moghe

University of Kentucky Doctoral Dissertations

Spatio-temporal variation in activation rates during ventricular fibrillation (VF)provides insight into mechanisms of sustained re-entry during VF. This study had three objectives related to spatio-temporal dynamics in activation rates during VF.

The first objective was to quantify spatio-temporal variability in activation rates,that is, in dominant frequencies, computed from epicardial electrograms recorded during VF in swine. Results showed that temporally and spatially, dominant frequencies variedas much as 20% of the mean dominant frequency, and the mean dominant frequencies increased during first 30 sec of VF. These results suggest that activation rates are nonstationary during VF.

The second objective of the study …

Mysterious Rectal Bleeding In A Female Adolescent, Hatim A. Omar

Pediatrics Faculty Publications

A 15-year-old female referred to our adolescent clinic for further evaluation of rectal bleeding was seen a week earlier in the acute care clinic with a two-day history of bright red rectal bleeding. The physical examination at that time was reportedly normal, including the rectal exam. The blood count with differential, liver function tests, ESR, and barium enema were all within normal limits. The patient, however, continued to complain of rectal bleeding and this led to the referral. She was known in the adolescent clinic as having a history of learning disability and mild mental retardation. She was started on …

Labial Adhesion As A Complication Of Primary Genital Herpes In Young Women, Hatim A. Omar

Pediatrics Faculty Publications

Genital herpes is a common sexually transmitted disease in adolescents. It may be associated with significant morbidity if not diagnosed on time or not properly treated. The objective of this study was to determine the incidence of labial adhesion secondary to primary herpes in young women and the possible predisposing factors for this complication. The method was analysis of clinical data regarding primary genital herpes in young women seen in an adolescent outpatient clinic at a university hospital. Cases of primary genital herpes seen between December 1^st 1998 and November 30^th 1999 were included. A total of 34 …

Protection Against Traumatic Brain Injury, Stephen William Scheff

Sanders-Brown Center on Aging Faculty Patents

The present invention relates to therapeutic uses of cyclosporin A to reduce adverse effects of neural injury.

Estrogen Protects Against The Synergistic Toxicity By Hiv Proteins, Methamphetamine And Cocaine, Jadwiga Turchan, Caroline Anderson, Kurt F. Hauser, Qinmiao Sun, Jiayou Zhang, Ying Liu, Phyllis M. Wise, Inna Kruman, William Maragos, Mark P. Mattson, Rosemarie Booze, Avindra Nath

Neurology Faculty Publications

BACKGROUND: Human immunodeficiency virus (HIV) infection continues to increase at alarming rates in drug abusers, especially in women. Drugs of abuse can cause long-lasting damage to the brain and HIV infection frequently leads to a dementing illness. To determine how these drugs interact with HIV to cause CNS damage, we used an in vitro human neuronal culture characterized for the presence of dopaminergic receptors, transporters and estrogen receptors. We determined the combined effects of dopaminergic drugs, methamphetamine, or cocaine with neurotoxic HIV proteins, gp120 and Tat.

RESULTS: Acute exposure to these substances resulted in synergistic neurotoxic responses as measured by …

Hormonal And Barrier Methods Of Contraception, Oncogenic Human Papillomaviruses, And Cervical Squamous Intraepithelial Lesion Development, Ann L. Coker, Laura C. Sanders, Sharon M. Bond, Tsilya Gerasimova, Lucia Pirisi

CRVAW Faculty Journal Articles

We assessed the influence of hormonal (oral, injectable, or levonorgestrel [Norplant, Wyeth-Ayerst, Philadelphia, PA]) and barrier methods of contraception on the risk of cervical squamous intraepithelial lesions (SIL), while adjusting for high-risk (HR) HPV infection. Subjects were women receiving family planning services through the state health department clinics from 1995 to 1998. We selected 60 cases with high-grade cervical/SIL (HSIL) and 316 with low-grade cervical/SIL (LSIL) and controls (427 women with normal cervical cytology) and analyzed cervical DNA for HR-HPV, using Hybrid Capture I (Digene; Gaithersburg, MD).When assessing ever use, duration, recency, latency, and age at first use, neither oral …

Phosphonated Agents And Their Antiangiogenic And Antitumorigenic Use, Delwood C. Collins, Antonio Gagliardi, Peter Nickel

Obstetrics and Genecology Faculty Patents

Phosphonic acid agents are synthesized and characterized which are potent inhibitors of angiogenesis, tumorigenesis and metalloproteinase activity. Their method of use for the inhibition of angiogenesis and metalloproteinase and the treatment of tumors is also shown.

Combined Antagonist Compositions, Scott R. Hamann

Anesthesiology Faculty Patents

Novel compositions of a combination of nicotinic, opioid, serotonergic and/or adrenergic antagonists in combination with nicotinic and opioid agonists, anti-depressants, stimulants, non-steroidal anti-inflammatory drugs, and local anesthetics, such combinations being useful in the treatment of excitable system disorders, pain and psychiatric disorders, and methods of use thereof.

Estrogen-Induced Relaxation In Bovine Coronary Arteries In Vitro: Evidence For A New Mechanism, Jelica D. J. Kalenic, Rolando J. Ramirez, Stanley Einzig, William A. Neal, Hatim A. Omar

Pediatrics Faculty Publications

Numerous studies have shown estrogen to be vasoactive in various circulations. Our objective was to determine the effect of estrogen on isolated bovine coronary arteries and the possible mechanism. Bovine coronary arteries, precontracted with thromboxane mimetic U₄₆₆₁₉ were given doses (0.01-30μM) of 17Β-estradiol in the presence and absence of endothelium and these inhibitors: 10μM indomethacin (cyclooxygenase inhibitor), 10μM methylene blue (inhibits soluble guanylate cyclase), 100μM nitro-L-arginine (inhibits nitric oxide synthesis), 100μM isobutylmethylxanthine (phosphodiesterase inhibitor) and 30μM mifepristone (Ru₃₈₄₈₆ steroid receptor antagonist). Our results indicated that, estrogen, in the highest concentration used (30μM), elicited an acute dose-dependent relaxation of …