Digital Commons Network^™

Mad2 And Bubr1 Function In A Single Checkpoint Pathway That Responds To A Loss Of Tension, Katie Shannon, Julie C. Canman, Edward D. Salmon

Biological Sciences Faculty Research & Creative Works

The spindle checkpoint monitors microtubule attachment and tension at kinetochores to ensure proper chromosome segregation. Previously, PtK1 cells in hypothermic conditions (23°C) were shown to have a pronounced mitotic delay, despite having normal numbers of kinetochore microtubules. At 23°C, we found that PtK1 cells remained in metaphase for an average of 101 min, compared with 21 min for cells at 37°C. The metaphase delay at 23°C was abrogated by injection of Mad2 inhibitors, showing that Mad2 and the spindle checkpoint were responsible for the prolonged metaphase. Live cell imaging showed that kinetochore Mad2 became undetectable soon after chromosome congression. Measurements …

Consumer Health Information For Asians (Chia): A Collaborative Project, Deborah D. Halsted, Beatriz Varman, Marsha Sullivan, Lynne Nguyen

Library Staff Publications

According to the 2000 United States Census, the Asian population in Houston, Texas, has increased more than 67% in the last ten years. To supplement an already active consumer health information program, the staff of the Houston Academy of Medicine-Texas Medical Center Library worked with community partners to bring health information to predominantly Asian neighborhoods. Brochures on health topics of concern to the Asian community were translated and placed in eight informational kiosks in Asian centers such as temples and an Asian grocery store. A press conference and a ribbon cutting ceremony were held to debut the kiosks and to …

Malignancy In Oral Lichen Planus: A Review Of A Group From The Malaysian Population, Wei Cheong Ngeow

Research Publications (2000 to 2005)

The objective of this study was to determine the socio-demography (age, race and gender) of a group of Malaysian patients who were diagnosed as suffering from oral lichen planus (OLP). The occurrence of malignancy was also investigated. A total of 77 clinical and biopsy records of patients with OLP were studied. Females were affected more than males, with the female to male ratio being 2:1. Middle-aged Indian and Chinese females tend to be affected by OLP when compared with the rest of the population. Only 19 patients returned for further follow-up. One adult Indian female with a six-year history of …

Child, Parent, And Peer Predictors Of Early-Onset Substance Use: A Multisite Longitudinal Study, Julie B Kaplow, Patrick J Curran, Kenneth A Dodge

Faculty, Staff and Students Publications

The purpose of this study was to identify kindergarten-age predictors of early-onset substance use from demographic, environmental, parenting, child psychological, behavioral, and social functioning domains. Data from a longitudinal study of 295 children were gathered using multiple-assessment methods and multiple informants in kindergarten and 1st grade. Annual assessments at ages 10, 11, and 12 reflected that 21% of children reported having initiated substance use by age 12. Results from longitudinal logistic regression models indicated that risk factors at kindergarten include being male, having a parent who abused substances, lower levels of parental verbal reasoning, higher levels of overactivity, more thought …

Fibroblast Growth Factor–Specific Modulation Of Cellular Response By Syndecan-4, Arie Horowitz, Eugene Tkachenko, Michael Simons

Dartmouth Scholarship

Proteoglycans participate in growth factor interaction with the cell surface through their heparan sulfate chains (HS), but it is not known if they are otherwise involved in growth factor signaling. It appears now that the syndecan-4 core protein, a transmembrane proteoglycan shown previously to bind phosphatidylinositol 4,5-bisphosphate (PIP(2)) and activate PKC alpha, participates in mediating the effects of fibroblast growth factor (FGF)2 on cell function. Mutations in the cytoplasmic tail of syndecan-4 that either reduced its affinity to PIP(2) (PIP(2)(-)) or disrupted its postsynaptic density 95, disk large, zona occludens-1 (PDZ)-dependent binding (PDZ(-)) produced a FGF2-specific dominant negative phenotype in …

Searching For The Middle Ground: Mechanisms Of Chromosome Alignment During Mitosis, Tarun M. Kapoor, Duane A. Compton

Dartmouth Scholarship

The contributions of key molecules predicted to align chromosomes at the center of the mitotic spindle have been recently examined. New results dictate that models for how chromosomes align during the early stages of mitosis must be revised to integrate properties of microtubule-based motor proteins as well as microtubule dynamics.

Hepatic Steatosis And Its Relationship To Transplantation., Charles J. Imber, Shawn D. St Peter, Ashok Handa, Peter J. Friend

Manuscripts, Articles, Book Chapters and Other Papers

Fatty infiltration of the liver is common in the brain-dead donor population and has a strong correlation with primary nonfunction after cold preservation, a condition that is catastrophic to liver transplant recipients. This literature review examines factors associated with the development, diagnosis, quantification, and clinical management of this difficult condition.

Neural Systems For Visual Orienting And Their Relationships To Spatial Working Memory, Maurizio Corbetta, J. Michelle Kincade, Gordon Shulman

Open Access Publications

We investigated neural correlates of human visual orienting using event-related functional magnetic resonance imaging (fMRI). When subjects voluntarily directed attention to a peripheral location, we recorded robust and sustained signals uniquely from the intraparietal sulcus (IPs) and superior frontal cortex (near the frontal eye field, FEF). In the ventral IPs and FEF only, the blood oxygen level dependent signal was modulated by the direction of attention. The IPs and FEF also maintained the most sustained level of activation during a 7-sec delay, when subjects maintained attention at the peripheral cued location (working memory). Therefore, the IPs and FEF form a …

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 …

Breast Cancer On The World Wide Web: Cross Sectional Survey Of Quality Of Information And Popularity Of Websites, Funda Meric, Elmer V Bernstam, Nadeem Q Mirza, Kelly K Hunt, Frederick C Ames, Merrick I Ross, Henry M Kuerer, Raphael E Pollock, Mark A Musen, S Eva Singletary

Faculty, Staff and Student Publications

OBJECTIVES: To determine the characteristics of popular breast cancer related websites and whether more popular sites are of higher quality.

DESIGN: The search engine Google was used to generate a list of websites about breast cancer. Google ranks search results by measures of link popularity---the number of links to a site from other sites. The top 200 sites returned in response to the query "breast cancer" were divided into "more popular" and "less popular" subgroups by three different measures of link popularity: Google rank and number of links reported independently by Google and by AltaVista (another search engine).

MAIN OUTCOME …

Short-Circuiting Long-Lived Humoral Immunity By The Heightened Engagement Of Cd40, Loren D. Erickson, Brigit G. Durell, Laura A. Vogel, Brian P. Connor, Marilia Cascalho, Teruhito Yasui, Hitoshi Kikutani, Randolph J. Noelle

Dartmouth Scholarship

Agonistic αCD40 Ab’s have been shown to be potent immune adjuvants for both cell- and humoral-mediated immunity. While enhancing short-lived humoral immunity, the administration of a CD40 agonist during thymus-dependent immune responses ablates germinal center formation, prematurely terminates the humoral immune response, blocks the generation of B cell memory, and prevents the generation of long-lived bone marrow plasma cells. Interestingly, some of these effects of heightened CD40 engagement could be mimicked by enhancing the magnitude of antigen-specific T cell help. Taken together, these studies demonstrate that as the magnitude of CD40 signaling intensifies, the fate of antigen-reactive B cells can …

Reduction In The Incidence Of Type 2 Diabetes With Lifestyle Intervention Or Metformin., William C. Knowler, Elizabeth Barrett-Connor, Sarah E. Fowler, Richard F. Hamman, John M. Lachin, Elizabeth A. Walker, David M. Nathan, P. G. Watson, J. T. Mendoza, K. A. Smith, J. Caro, B. Goldstein, C. Lark, L. Menefee, L. Murphy, C. Pepe, J. M. Spandorfer

Department of Medicine Faculty Papers

BACKGROUND: Type 2 diabetes affects approximately 8 percent of adults in the United States. Some risk factors--elevated plasma glucose concentrations in the fasting state and after an oral glucose load, overweight, and a sedentary lifestyle--are potentially reversible. We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes.

METHODS: We randomly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo, metformin (850 mg twice daily), or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least …

Triplet Repeat Dna Structures And Human Genetic Disease: Dynamic Mutations From Dynamic Dna., Richard R. Sinden, Vladimir N. Potaman, Elena A. Oussatcheva, Christopher E. Pearson, Yuri L. Lyubchenko, Luda S. Shlyakhtenko

Journal Articles: Pharmaceutical Sciences

Fourteen genetic neurodegenerative diseases and three fragile sites have been associated with the expansion of (CTG)n (CAG)n, (CGG)n (CCG)n, or (GAA)n (TTC)n repeat tracts. Different models have been proposed for the expansion of triplet repeats, most of which presume the formation of alternative DNA structures in repeat tracts. One of the most likely structures, slipped strand DNA, may stably and reproducibly form within triplet repeat sequences. The propensity to form slipped strand DNA is proportional to the length and homogeneity of the repeat tract. The remarkable stability of slipped strand DNA may, in part, be due to loop-loop interactions facilitated …

Vanadate-Induced Expression Of Hypoxia-Inducible Factor 1Α And Vascular Endothelial Growth Factor Through Phosphatidylinositol 3-Kinase/Akt Pathway And Reactive Oxygen Species, Ning Gao, Min Ding, Jenny Z. Zheng, Zhuo Zhang, Stephen S. Leonard, Ke Jian Liu, Xianglin Shi, Bing-Hua Jiang

Faculty & Staff Scholarship

No abstract provided.

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 …

Presented Antigen From Damaged Pancreatic Beta Cells Activates Autoreactive T Cells In Virus-Mediated Autoimmune Diabetes., Marc S. Horwitz, Alex Ilic, Cody Fine, Enrique Rodriguez, Nora Sarvetnick

Journal Articles: Regenerative Medicine

The induction of autoimmunity by viruses has been attributed to numerous mechanisms. In mice, coxsackievirus B4 (CB4) induces insulin-dependent diabetes mellitus (IDDM) resembling the final step of disease progression in humans. The immune response following the viral insult clearly precipitates IDDM. However, the molecular pathway between viral infection and the subsequent activation of T cells specific for islet antigen has not been elucidated. These T cells could become activated through exposure to sequestered antigens released by damaged beta cells, or they could have responded to factors secreted by the inflammatory response itself. To distinguish between these possibilities, we treated mice …

Development And Characterization Of A Reconstituted Yeast Translation Initiation System, Mikkel A. Algire, David Maag, Peter Savio, Michael G. Acker, Salvador Z. Tarun Jr., Alan B. Sachs, Katsura Asano, Klaus H. Nelson, Deanne S. Olsen, Lon Phan, Alan G. Hinnebusch, Jon R. Lorsch, J.R.

Biology

To provide a bridge between in vivo and in vitro studies of eukaryotic translation initiation, we have developed a reconstituted translation initiation system using components from the yeast Saccharomyces cerevisiae. We have purified a minimal set of initiation factors (elFs) that, together with yeast 80S ribosomes, GTP, and initiator methionyl-tRNA, are sufficient to assemble active initiation complexes on a minimal mRNA template. The kinetics of various steps in the pathway of initiation complex assembly and the formation of the first peptide bond in vitro have been explored. The formation of active initiation complexes in this system is dependent on ribosomes, …

Caveolin-1 Expression Enhances Endothelial Capillary Tubule Formation, Jun Liu, Xiao Bo Wang, David S. Park, Michael P. Lisanti

Faculty & Staff Scholarship

No abstract provided.

Comparing Communication Technology On Chinese, English, And Spanish Diabetes Web Sites, Yanko F Michea, Karen Pancheri, Yang Gong, Elmer Bernstam

Faculty, Staff and Student Publications

Technological and cultural factors influence access to health information on the web in multifarious ways. We evaluated structural differences and availability of communication services on the web in three diverse language and cultural groups: Chinese, English, and Spanish. A total of 382 web sites were analyzed: 144 were English language sites (38%), 129 were Chinese language sites (34%), and 108 were Spanish language sites (28%). We did not find technical differences in the number of outgoing links per domain or the total availability of communication services between the three groups. There were differences in the distribution of available services between …

Nipple Aspirate Cytology And Pathologic Parameters Predict Residual Cancer And Nodal Involvement After Excisional Breast Biopsy., E R Sauter, H Ehya, A Mammen, G Klein

Department of Surgery Faculty Papers

We previously demonstrated that abnormal nipple aspirate fluid (NAF) cytology predicted residual breast cancer (RC) and tumour size after excisional biopsy (EB), although normal NAF cytology did not exclude RC. Tumour size correlates with the risk of lymph node (LN) metastases. LN metastases provide prognostic information allowing medical and radiation oncologists to determine the need for adjuvant therapy. We hypothesized that pathologic factors known after EB, combined with NAF cytology, would predict with a high degree of accuracy the presence of RC and LN spread. NAF cytology and pathologic parameters: tumour distance from biopsy margins, multifocal and multicentric disease, sub-type …

Vdac-Dependent Permeabilization Of The Outer Mitochondrial Membrane By Superoxide Induces Rapid And Massive Cytochrome C Release., M Madesh, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Enhanced formation of reactive oxygen species (ROS), superoxide (O2*-), and hydrogen peroxide (H2O2) may result in either apoptosis or other forms of cell death. Here, we studied the mechanisms underlying activation of the apoptotic machinery by ROS. Exposure of permeabilized HepG2 cells to O2*- elicited rapid and massive cytochrome c release (CCR), whereas H2O2 failed to induce any release. Both O2*- and H2O2 promoted activation of the mitochondrial permeability transition pore by Ca2+, but Ca2+-dependent pore opening was not required for O2*--induced CCR. Furthermore, O2*- alone evoked CCR without damage of the inner mitochondrial membrane barrier, as mitochondrial membrane potential …

A Longitudinal Investigation Of Information Processing And Cognitive Organization In Clinical Depression: Stability Of Schematic Interconnectedness., D J Dozois, K S Dobson

Psychology Publications

This study longitudinally investigated information processing and cognitive organization in clinical depression. The main hypothesis was that individuals whose depression had remitted would show a significant cognitive shift on information processing (e.g., deactivation of negative processing) but not on cognitive organizational tasks, Forty-five individuals with clinical depression completed 2 information processing and 2 cognitive organizational tasks at initial assessment. At 6-month follow-up, the sample (23 remitted, 22 stable depressed) was readministered the tasks. As expected, information processing shifted significantly in individuals who had improved symptomatically, whereas negative cognitive organizational indices remained stable. The implications of these results are discussed as …

Proteolytic Release Of Cd44 Intracellular Domain And Its Role In The Cd44 Signaling Pathway., I Okamoto, Y Kawano, D Murakami, T Sasayama, N Araki, T Miki, A J Wong, H Saya

Department of Microbiology and Immunology Faculty Papers

CD44 is a widely distributed cell surface adhesion molecule and is implicated in diverse biological processes. However, the nature of intracellular signaling triggered by CD44 remains to be elucidated. Here, we show that CD44 undergoes sequential proteolytic cleavage in the ectodomain and intracellular domain, resulting in the release of a CD44 intracellular domain (ICD) fragment. Consequently, CD44ICD acts as a signal transduction molecule, where it translocates to the nucleus and activates transcription mediated through the 12-O-tetradecanoylphorbol 13-acetate-responsive element, which is found in numerous genes involved in diverse cellular processes. Expression of an uncleavable CD44 mutant as well as metalloprotease inhibitor …

Role Of Protein Kinase C-Delta In The Regulation Of Collagen Gene Expression In Scleroderma Fibroblasts, Sergio A. Jimenez, Svetlana Gaidarova, Biagio Saitta, Nora Sandorfi, David J. Herrich, Joan C. Rosenbloom, Umberto Kucich, William R. Abrams, Joel Rosenbloom

Selected Works of Sergio Jiménez, MD, MACR

Working with cultured dermal fibroblasts derived from control individuals and patients with systemic sclerosis (SSc), we have examined the effects of protein kinase C-delta (PKC-delta) on type I collagen biosynthesis and steady-state levels of COL1A1 and COL3A1 mRNAs. Rottlerin, a specific inhibitor of PKC-delta, exerted a powerful, dose-dependent inhibition of type I and type III collagen gene expression in normal and SSc cells. Optimal rottlerin concentrations caused a 70-90% inhibition of type I collagen production, a >80% reduction in COL1A1 mRNA, and a >70% reduction in COL3A1 mRNA in both cell types. In vitro nuclear transcription assays and transient transfections …

Critical Analysis Of Cerebrovascular Autoregulation During Repeated Head-Up Tilt., R L Hughson, M R Edwards, D D O'Leary, J K Shoemaker

Kinesiology Publications

BACKGROUND AND PURPOSE: Cerebrovascular autoregulation has been described with a phase lead of cerebral blood flow preceding changes in cerebral perfusion pressure (CPP), but there has been less focus on the effect of CPP on cerebral vascular resistance. We investigated these relations during spontaneous fluctuations (control) and repeated head-up tilt.

METHODS: Eight healthy adults were studied in supine rest and repeated tilt with 10-second supine, 10 seconds at 45 degrees head-up tilt for a total of 12 cycles. Cerebral blood flow was estimated from mean flow velocity (MFV) by transcranial Doppler ultrasound, CPP was estimated from corrected finger pressure (CPP(F)), …

The Chromokinesin Kid Is Necessary For Chromosome Arm Orientation And Oscillation, But Not Congression, On Mitotic Spindles, Aime A. Levesque, Duane A. Compton

Dartmouth Scholarship

Chromokinesins have been postulated to provide the polar ejection force needed for chromosome congression during mitosis. We have evaluated that possibility by monitoring chromosome movement in vertebrate-cultured cells using time-lapse differential interference contrast microscopy after microinjection with antibodies specific for the chromokinesin Kid. 17.5% of cells injected with Kid-specific antibodies have one or more chromosomes that remain closely opposed to a spindle pole and fail to enter anaphase. In contrast, 82.5% of injected cells align chromosomes in metaphase, progress to anaphase, and display chromosome velocities not significantly different from control cells. However, injected cells lack chromosome oscillations, and chromosome orientation …

Eliciting The Low-Activity Aldehyde Dehydrogenase Asian Phenotype By An Antisense Mechanism Results In An Aversion To Ethanol., E Garver, Tu Gc, Q N Cao, M Aini, F Zhou, Y Israel

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

A mutation in the gene encoding for the liver mitochondrial aldehyde dehydrogenase (ALDH2-2), present in some Asian populations, lowers or abolishes the activity of this enzyme and results in elevations in blood acetaldehyde upon ethanol consumption, a phenotype that greatly protects against alcohol abuse and alcoholism. We have determined whether the administration of antisense phosphorothioate oligonucleotides (ASOs) can mimic the low-activity ALDH2-2 Asian phenotype. Rat hepatoma cells incubated for 24 h with an antisense oligonucleotide (ASO-9) showed reductions in ALDH2 mRNA levels of 85% and ALDH2 (half-life of 22 h) activity of 55% equivalent to a >90% inhibition in ALDH2 …

Tractor Driving Among Kentucky Farm Youth: Results From The Farm Family Health And Hazard Surveillance Project, Steven R. Browning, Susan C. Westneat, Raeanne Szeluga

Epidemiology and Environmental Health Faculty Publications

This article documents the extent of children's involvement in tractor operations among a representative sample of Kentucky children living and working on family farms. Specifically, we describe children's exposures to tractor-related work activities, profile their use of the tractor (number of days worked), and assess compliance with generally recommended safety measures, such as using tractors equipped with ROPS (rollover protective structures), avoiding riding as passengers on tractors, and operating tractors on public roadways. Data for this study were collected in 1994 and 1995 as part of the NIOSH-sponsored Farm Family Health and Hazard Surveillance Project (FFHHSP). Despite recognition in the …

The Toxoplasma Gondii Protein Rop2 Mediates Host Organelle Association With The Parasitophorous Vacuole Membrane, Anthony P. Sinai, Keith A. Joiner

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Toxoplasma gondii replicates within a specialized vacuole surrounded by the parasitophorous vacuole membrane (PVM). The PVM forms intimate interactions with host mitochondria and endoplasmic reticulum (ER) in a process termed PVM–organelle association. In this study we identify a likely mediator of this process, the parasite protein ROP2. ROP2, which is localized to the PVM, is secreted from anterior organelles termed rhoptries during parasite invasion into host cells. The NH₂-terminal domain of ROP2 (ROP2hc) within the PVM is exposed to the host cell cytosol, and has characteristics of a mitochondrial targeting signal. In in vitro assays, ROP2hc is …