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Recent Advances In Basic Neurosciences And Brain Disease: From Synapses To Behavior, Guo-Qiang Bi, Vadim Bolshakov, Guojun Bu, Catherine M. Cahill, Zhou-Feng Chen, Graham L. Collingridge, Robin L. Cooper, Jens R. Coorssen, Alaa El-Husseini, Vasco Galhardo, Wen-Biao Gan, Jianguo Gu, Kazuhide Inoue, John Isaac, Koichi Iwata, Zhengping Jia, Bong-Kiun Kaang, Mikito Kawamata, Satoshi Kida, Eric Klann, Tatsuro Kohno, Min Li, Xiao-Jiang Li, John F. Macdonald, Karim Nader, Peter V. Nguyen, Uhtaek Oh, Ke Ren, John C. Roder, Michael W. Salter, Weihong Song, Shuzo Sugita, Shao-Jun Tang, Yuanxiang Tao, Yu Tian Wang, Newton Woo, Melanie A. Woodin, Zhen Yan, Megumu Yoshimura, Ming Xu, Zao C. Xu, Xia Zhang, Mei Zhen, Min Zhuo

Biology Faculty Publications

Understanding basic neuronal mechanisms hold the hope for future treatment of brain disease. The 1st international conference on synapse, memory, drug addiction and pain was held in beautiful downtown Toronto, Canada on August 21-23, 2006. Unlike other traditional conferences, this new meeting focused on three major aims: (1) to promote new and cutting edge research in neuroscience; (2) to encourage international information exchange and scientific collaborations; and (3) to provide a platform for active scientists to discuss new findings. Up to 64 investigators presented their recent discoveries, from basic synaptic mechanisms to genes related to human brain disease. This meeting …

Evidence That Talin Alternative Splice Variants From Ciona Intestinalis Have Different Roles In Cell Adhesion, Richard H. Singiser, Richard O. Mccann

Molecular and Cellular Biochemistry Faculty Publications

BACKGROUND: Talins are large, modular cytoskeletal proteins found in animals and amoebozoans such as Dictyostelium discoideum. Since the identification of a second talin gene in vertebrates, it has become increasingly clear that vertebrate Talin1 and Talin2 have non-redundant roles as essential links between integrins and the actin cytoskeleton in distinct plasma membrane-associated adhesion complexes. The conserved C-terminal I/LWEQ module is important for talin function. This structural element mediates the interaction of talins with F-actin. The I/LWEQ module also targets mammalian Talin1 to focal adhesion complexes, which are dynamic multicomponent assemblies required for cell adhesion and cell motility. Although Talin1 is …

The Pulmonary Effects Of Intravenous Adenosine In Asthmatic Subjects, Nausherwan K. Burki, Mahmud Alam, Lu-Yuan Lee

Physiology Faculty Publications

BACKGROUND: We have shown that intravenous adenosine in normal subjects does not cause bronchospasm, but causes dyspnea, most likely by an effect on vagal C fibers in the lungs [Burki et al. J Appl Physiol 2005; 98:180-5]. Since airways inflammation and bronchial hyperreactivity are features of asthma, it is possible that intravenous adenosine may be associated with an increased intensity of dyspnea, and may cause bronchospasm, as noted anecdotally in previous reports.

METHODS: We compared the effects of placebo and 10 mg intravenous adenosine, in 6 normal and 6 asthmatic subjects.

RESULTS: Placebo injection had no significant (p > 0.05) effect …

Gene Expression Patterns That Predict Sensitivity To Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors In Lung Cancer Cell Lines And Human Lung Tumors, Justin M. Balko, Anil Potti, Christopher Saunders, Arnold J. Stromberg, Eric B. Haura, Esther P. Black

Statistics Faculty Publications

BACKGROUND: Increased focus surrounds identifying patients with advanced non-small cell lung cancer (NSCLC) who will benefit from treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI). EGFR mutation, gene copy number, coexpression of ErbB proteins and ligands, and epithelial to mesenchymal transition markers all correlate with EGFR TKI sensitivity, and while prediction of sensitivity using any one of the markers does identify responders, individual markers do not encompass all potential responders due to high levels of inter-patient and inter-tumor variability. We hypothesized that a multivariate predictor of EGFR TKI sensitivity based on gene expression data would offer a …

Navigating Adolescence With A Chronic Health Condition: A Perspective On The Psychological Effects Of Hair-An Syndrome On Adolescent Girls, Kimberly K. Mcclanahan, Hatim A. Omar

Pediatrics Faculty Publications

HAIR-AN syndrome is a subphenotype of polycystic ovary syndrome and is characterized by acne, obesity, hirsutism, and acanthosis nigricans. It usually manifests in early adolescence, a time of significant developmental change in females across physical, cognitive, social, and emotional domains. We contend that adolescent development for females is difficult, even in the best of circumstances, and having a chronic health condition, like HAIR-AN syndrome, will likely impact the afflicted individual's development and psychological well-being. While many researchers have discussed the long-term health effects of HAIR-AN and similar disorders, little has been written about the potential psychological sequelae of HAIR-AN on …

Gene Order Data From A Model Amphibian (Ambystoma): New Perspectives On Vertebrate Genome Structure And Evolution, Jeramiah J. Smith, S. Randal Voss

Biology Faculty Publications

BACKGROUND: Because amphibians arise from a branch of the vertebrate evolutionary tree that is juxtaposed between fishes and amniotes, they provide important comparative perspective for reconstructing character changes that have occurred during vertebrate evolution. Here, we report the first comparative study of vertebrate genome structure that includes a representative amphibian. We used 491 transcribed sequences from a salamander (Ambystoma) genetic map and whole genome assemblies for human, mouse, rat, dog, chicken, zebrafish, and the freshwater pufferfish Tetraodon nigroviridis to compare gene orders and rearrangement rates.

RESULTS: Ambystoma has experienced a rate of genome rearrangement that is substantially lower than mammalian …

From Healing The Whole Person: An Argument For Therapeutic Touch As A Complement To Traditional Medical Practice, Marlene B. Huff, Kimberly K. Mcclanahan, Hatim A. Omar

Pediatrics Faculty Publications

The growing popularity and use of therapeutic touch (TT) is an issue that has generated controversy and concern within the medical community. While anecdotal and traditional scientific evidence suggest that TT would be an advantageous addition for clinics and hospitals to include in their armamentarium of complementary interventions within the realm of traditional medicine, TT has not become widely available in the U.S. One reason for the lack of availability may be the dearth of conclusive scientific support for TT's efficacy and, therefore, its inclusion in clinic and hospital treatment planning would give it the appearance of legitimate practice, which …

Pregnant Teenager Involvement In Sexual Activity And The Social Context, Maria José Carvalho Sant'anna, Júlia Kerr Catunda, Kepler Alencar Mendes Carvalho, Verônica Coates, Hatim A. Omar

Pediatrics Faculty Publications

Pregnancy during adolescence represents a challenge to society as a whole. Its incidence is increasing and brings about social and medical consequences to both the teen mothers and their children. The purpose of this study was to evaluate pregnant teenager involvement in sexual activity and the social context. The group studied comprised 152 pregnant teenagers attending the Department of Pediatrics, Santa Casa de Sao Paulo (SCSP) General Hospital. All information was analyzed. The age at first intercourse was 14.2 years and the average period between first intercourse and pregnancy was 1.4 years. Most pregnancies (75%) were neither planned nor wanted, …

Correlation Between Number Of Retrieved Oocytes And Pregnancy Rate After In Vitro Fertilization/Intracytoplasmic Sperm Infection, Tanya Timeva, Tanya Milachich, Irena Antonova, Tanya Arabaji, Atanas Shterev, Hatim A. Omar

Pediatrics Faculty Publications

The implementation of safe and maximally effective ovarian stimulation is a major aim for in vitro fertilization (IVF) teams. The goal of controlled ovarian hyperstimulation (COH) is to supply enough oocytes with normal maturation to insure the consequent biological procedures. A variety of different stimulation protocols have been suggested and an individual selection of the correct stimulation protocol is mandatory. The aim of the present study is to evaluate the correlation between number of retrieved oocytes and clinical pregnancy rate (CPR) after IVF or intracytoplasmic sperm injection (ICSI) procedures. We reviewed 1017 cycles in a total of 975 patients. The …

Dissociation Of Automatic And Strategic Lexical-Semantics: Functional Magnetic Resonance Imaging Evidence For Differing Roles Of Multiple Frontotemporal Regions, Brian T. Gold, David A. Balota, Sara J. Jones, David K. Powell, Charles D. Smith, Anders H. Andersen

Neuroscience Faculty Publications

Behavioral research has demonstrated three major components of the lexical-semantic processing system: automatic activation of semantic representations, strategic retrieval of semantic representations, and inhibition of competitors. However, these component processes are inherently conflated in explicit lexical-semantic decision tasks typically used in functional magnetic resonance imaging (fMRI) research. Here, we combine the logic of behavioral priming studies and the neurophysiological phenomenon of fMRI priming to dissociate the neural bases of automatic and strategic lexical-semantic processes across a series of three studies. A single lexical decision task was used in all studies, with stimulus onset asynchrony or linguistic relationship between prime and …

Biomolecular Study Of The Correlation Between Papillomatosis Of The Vulvar Vestibule In Adolescents And Human Papillomavirus, Geni Beznos, Verônica Coates, Jose Focchi, Hatim A. Omar

Pediatrics Faculty Publications

The main goal of this study was to investigate, through a biomolecular study, the correlation between papillomatosis of the vulvar vestibule and human papillomavirus (HPV) infection, as well as to establish the necessity of treatment. A total of 44 female adolescents between 12 and 18 years of age were selected through a prospective study with a confirmed diagnosis of papillomatosis of the vulvar vestibule. Vulvar biopsies were obtained for the histological and biomolecular detection of HPV DNA through polymerase chain reaction (PCR). Twenty (45%) adolescents were virgins (group A), the other 24 (55%) were sexually active. The virgin adolescents (group …

A Pilot Study: Attention Deficit Hyperactivity Disorder, Sensation Seeking, And Pubertal Changes, Catherine A. Martin, Greg Guenthner, Christopher Bingcang, W. Jackson Smith, Thomas E. Curry, Hatim A. Omar, Mary Kay Rayens, Tom H. Kelly

Pediatrics Faculty Publications

This study was designed to examine the relationship of pubertal changes and sensation seeking (SS) in adolescents with Attention Deficit Hyperactivity Disorder (ADHD). Patients with current or past histories of uncomplicated stimulant medication use for ADHD between the ages of 11 and 15 (13 ± 1.5) were recruited from a Child Psychiatry and a General Pediatric Clinic. SS was measured using the SS Scale for Children. Pubertal development was measured using Tanner staging, free testosterone, and DHEAS. Subjects and their parent were interviewed with the Diagnostic Interview Schedule for Children (DISC). SS total score was correlated with Tanner stage, free …

Depression, Sensation Seeking, And Maternal Smoking As Predictors Of Adolescent Cigarette Smoking, Judy Van De Venne, Kay Bradford, Catherine A. Martin, Megan Cox, Hatim A. Omar

Family Sciences Faculty Publications

The purpose of this study was to examine maternal and adolescent depression, maternal and teen sensation seeking, and maternal smoking, and their associations with adolescent smoking. Data were collected from a sample of 47 male and 66 female adolescents (ages 11-18 years) and their mothers from three different health clinics. The findings indicated that maternal sensation seeking was linked indirectly with adolescent smoking through teen sensation seeking, both of which were significantly associated with teen smoking (β = 0.29, p < 0.001 and β = 0.32, p < 0.001, respectively). Teen depression was associated positively with teen smoking (β = 0.24, p < 0.01) when controlling for sensation seeking behaviors. Maternal smoking was also directly linked to adolescent smoking (β = 0.20, p < 0.05). These findings underscore a potentially important role of sensation seeking in the origins of adolescent smoking, and clarify pathways of influence with regard to maternal attitudes and behaviors in subsequent teenage nicotine use.

Why Dentists Should Become Oral Physicians: A Response To Dr. Donald Giddon's "Why Dentists Should Be Called Oral Physicians Now", David A. Nash

Oral Health Science Faculty Publications

No abstract provided.

Incidence Of Galactorrhea In Young Women Using Depot-Medroxyprogesterone Acetate, Hatim A. Omar, Rana M. Zakharia, Shibani Kanungo, Marlene B. Huff, Kimberly K. Mcclanahan

Pediatrics Faculty Publications

Galactorrhea is rarely mentioned as a possible side effect of the use of Depot-Medroxyprogesterone Acetate (DMPA). Over the last few years, we have noticed an increased number of patients complaining of galactorrhea. A review of clinical data showed that between 1999 and 2005, 360 adolescents in our clinic used DMPA for at least 6 months. After medical follow-up, 13 (3.6%) of these patients were found to have developed galactorrhea. The mean age of the patients was 19.4 years with a range from 13-24. Prolactin levels in these patients were normal, and in all subjects, the galactorrhea resolved spontaneously within the …

Spontaneous Intracranial Arterial Dissection In The Young: Diagnosis By Ct Angiography, William C. Robertson, Curtis A. Given

Neurology Faculty Publications

BACKGROUND: Spontaneous carotid artery dissections have been rarely reported in children. Diagnosis has traditionally been confirmed by catheter arteriography. More recently diagnosis has been made by magnetic resonance imaging and magnetic resonance angiography; however the sensitivity of these techniques has yet to be determined. The authors are unaware of reports of carotid dissection confirmed by dynamic computed tomography (computerized tomographic arteriography) in the young.

CASE PRESENTATION: We recently evaluated a fourteen year-old male following the development of transient neurologic symptoms. There was no antecedent illness or trauma. Dynamic computed tomography revealed an intracranial dissection involving the supraclinoid segment of the …

Successful Treatment Of Depot Medroxyprogesterone Acetate-Related Vaginal Bleeding Improves Continuation Rates In Adolescents, Kristin M. Rager, Amy Fowler, Hatim A. Omar

Pediatrics Faculty Publications

High discontinuation rates for depot medroxyprogesterone acetate (DMPA) in adolescents may contribute to the number of unintended pregnancies. Many cite vaginal bleeding as a reason for discontinuing DMPA use. In this study, we attempted to determine if treating DMPA-associated vaginal bleeding with monophasic oral contraceptive pills (OCP) raised continuation rates. A total of 131 patients who reported vaginal bleeding while on DMPA were included in this study and 83 were treated with monophasic OCP. Of those who received OCP, 38.7% reported that vaginal bleeding stopped completely, 51.8% reported that vaginal bleeding stopped temporarily, and 6.0% reported no change. Overall, 94% …

Holistic Health: Does It Really Include Mental Health?, Kimberly K. Mcclanahan, Marlene B. Huff, Hatim A. Omar

Pediatrics Faculty Publications

Holistic health, incorporating mind and body as equally important and unified components of health, is a concept utilized in some health care arenas in the United States (U.S.) over the past 30 years. However, in the U.S., mental health is not seen as conceptually integral to physical health and, thus, holistic health cannot be realized until the historical concept of mind-body dualism, continuing stigma regarding mental illness, lack of mental health parity in insurance, and inaccurate public perceptions regarding mental illness are adequately addressed and resolved. Until then, mental and physical health will continue to be viewed as disparate entities …

Clinical Holistic Medicine: Holistic Sexology And Acupressure Through The Vagina (Hippocratic Pelvic Massage), Søren Ventegodt, Birgitte Clausen, Hatim A. Omar, Joav Merrick

Pediatrics Faculty Publications

Many gynecological and sexological problems (like urine incontinence, chronic pelvic pains, vulvodynia, and lack of lust, excitement, and orgasm) are resistant to standard medical treatment. In our work at the Research Clinic for Holistic Medicine in Copenhagen, we have found that vaginal acupressure, or Hippocratic pelvic massage, can help some of these problems. Technically, it is a very simple procedure as it corresponds to the explorative phase of the standard pelvic examination, supplemented with the patient's report on the feelings it provokes and the processing and integration of these feelings. Sometimes it can be very difficult to control the emotions …

Length-Dependent Degradation Of Single-Stranded 3' Ends By The Werner Syndrome Protein (Wrn): Implications For Spatial Orientation And Coordinated 3' To 5' Movement Of Its Atpase/Helicase And Exonuclease Domains, Amrita Machwe, Liren Xiao, David K. Orren

Toxicology and Cancer Biology Faculty Publications

BACKGROUND: The cancer-prone and accelerated aging disease Werner syndrome is caused by loss of function of the WRN gene product that possesses ATPase, 3' to 5' helicase and 3' to 5' exonuclease activities. Although WRN has been most prominently suggested to function in telomere maintenance, resolution of replication blockage and/or recombinational repair, its exact role in DNA metabolism remains unclear. WRN is the only human RecQ family member to possess both helicase and exonuclease activity, but the mechanistic relationship between these activities is unknown. In this study, model single-stranded and 3' overhang DNA substrates of varying length and structure were …

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 …

Androgen Excess Disorders In Women: The Severe Insulin-Resistant Hyperandrogenic Syndrome, Hair-An, Kristin M. Rager, Hatim A. Omar

Pediatrics Faculty Publications

HAIR-AN syndrome (hyperandrogenism, insulin resistance, acanthosis nigricans) is a subset of the polycystic ovary syndrome, where the patients demonstrate severe insulin resistance. It is theorized that both genetic and environmental factors, such as obesity, give rise to the development of HAIR-AN. Diagnosis is primarily clinical, with laboratory values lending further support. Treatment is aimed at decreasing insulin resistance, regulating ovulation, and decreasing acne, acanthosis nigricans, and hirsutism.

Competition Between The Dna Unwinding And Strand Pairing Activities Of The Werner And Bloom Syndrome Proteins, Amrita Machwe, Enerlyn M. Lozada, Liren Xiao, David K. Orren

Toxicology and Cancer Biology Faculty Publications

BACKGROUND: The premature aging and cancer-prone Werner and Bloom syndromes are caused by defects in the RecQ helicase enzymes WRN and BLM, respectively. Recently, both WRN and BLM (as well as several other RecQ members) have been shown to possess a strand annealing activity in addition to the requisite DNA unwinding activity. Since an annealing function would appear to directly oppose the action of a helicase, we have examined in this study the dynamic equilibrium between unwinding and annealing mediated by either WRN or BLM.

RESULTS: Our investigation into the competition between annealing and unwinding demonstrates that, under standard reaction …

The Speciation Of Metals In Mammals Influences Their Toxicokinetics And Toxicodynamics And Therefore Human Health Risk Assessment, Robert A. Yokel, Stephen M. Lasley, David C. Dorman

Pharmaceutical Sciences Faculty Publications

Chemical form (i.e., species) can influence metal toxicokinetics and toxicodynamics and should be considered to improve human health risk assessment. Factors that influence metal speciation (and examples) include: (1) carrier-mediated processes for specific metal species (arsenic, chromium, lead and manganese), (2) valence state (arsenic, chromium, manganese and mercury), (3) particle size (lead and manganese), (4) the nature of metal binding ligands (aluminum, arsenic, chromium, lead, and manganese), (5) whether the metal is an organic versus inorganic species (arsenic, lead, and mercury), and (6) biotransformation of metal species (aluminum, arsenic, chromium, lead, manganese and mercury). The influence of speciation on metal …