Medicine and Health Sciences Commons^™

Pick1 Deficiency Causes Male Infertility In Mice By Disrupting Acrosome Formation, Nan (Tori) Xiao, Chuen Kam, Chong Shen, Wenying Jin, Junqi Wang, Kwong Man Lee, Liwen Jiang, Jun Xia

All Dugoni School of Dentistry Faculty Articles

Protein interacting with C kinase 1 (PICK1) is a peripheral membrane protein involved in protein trafficking, a function that has been well characterized in neurons. Here, we report that male mice deficient in PICK1 are infertile and have a phenotype resembling the human disease globozoospermia. The primary defect in the testes of Pick1-knockout mice was fragmentation of acrosomes in the early stages of spermiogenesis. This fragmentation was followed by defects in nuclear elongation and mitochondrial sheath formation, leading to round-headed sperm, reduced sperm count, and severely impaired sperm motility. We found that PICK1 interacted with Golgi-associated PDZ- and coiled-coil motif-containing …

Laparoscopic Treatment Of Pancreatic Pseudocysts In Children., Suzanne M. Yoder, Steven Rothenberg, Kuojen Tsao, Mark L. Wulkan, Todd A. Ponsky, Shawn D. St Peter, Daniel J. Ostlie, Timothy D. Kane

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Pancreatic pseudocysts are problematic sequelae of pancreatitis or pancreatic trauma causing persistent abdominal pain, nausea, and gastric outlet obstruction. Due to the low volume of disease in children, there is scant information in the literature on the operative management of pseudocysts with minimally invasive techniques. We conducted a multi-institutional review to illustrate several technical variations utilized in achieving laparoscopic cystgastrostomy in the pediatric population.

METHODS: A retrospective review was conducted of all patients who underwent laparoscopic cystgastrostomy in five institutions. Patient data, operative techniques, and postoperative course were analyzed.

RESULTS: There were 13 patients with a mean age of …

Comorbidities, Patient Knowledge, And Disease Management In A National Sample Of Patients With Copd, R Graham Barr, Bartolome R Celli, David M Mannino, Thomas Petty, Stephen I Rennard, Frank C Sciurba, James K Stoller, Byron M Thomashow, Gerard M Turino

Faculty, Staff and Student Publications

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States but is often undertreated. COPD often overlaps with other conditions such as hypertension and osteoporosis, which are less morbid but may be treated more aggressively. We evaluated the prevalence of these comorbid conditions and compared testing, patient knowledge, and management in a national sample of patients with COPD.

METHODS: A survey was administered by telephone in 2006 to 1003 patients with COPD to evaluate the prevalence of comorbid conditions, diagnostic testing, knowledge, and management using standardized instruments. The completion rate was 87%.

RESULTS: …

Coronary Steal Syndrome After Coronary Artery Bypass For Anomalous Aortic Origin Of A Coronary Artery., Benjamin A. Youdelman, Glenn J. Pelletier, C Igor Mesia, Marshall L. Jacobs

Department of Surgery Faculty Papers

Anomalous aortic origin of a coronary artery found in a symptomatic 9-year-old boy was initially treated with coronary artery bypass grafting using a left internal mammary artery anastomoses to the left anterior descending coronary artery, but resulted in coronary ischemia, likely from a steal phenomenon. Subsequent transection of the proximal left internal mammary artery with anastomosis to the ascending aorta, and coronary ostial enlargement, resulted in a durable treatment. We recommend caution in choosing coronary artery bypass grafting using a left internal mammary artery pedicle graft for the treatment of anomalous aortic origin of a coronary artery.

Smoking Enhances Risk For New External Genital Warts In Men, Dorothy J. Wiley, David Elashoff, Emmanuel V. Masongsong, Diane M. Harper

Dartmouth Scholarship

Repeat episodes of HPV-related external genital warts reflect recurring or new infections. No study before has been sufficiently powered to delineate how tobacco use, prior history of EGWs and HIV infection affect the risk for new EGWs. Behavioral, laboratory and examination data for 2,835 Multicenter AIDS Cohort Study participants examined at 21,519 semi-annual visits were evaluated. Fourteen percent (391/2835) of men reported or were diagnosed with EGWs at 3% (675/21,519) of study visits. Multivariate analyses showed smoking, prior episodes of EGWs, HIV infection and CD4+ T-lymphocyte count among the infected, each differentially influenced the risk for new EGWs.

Paracrine Sonic Hedgehog Signalling By Prostate Cancer Cells Induces Osteoblast Differentiation, Samantha M Zunich, Taneka Douglas, Maria Valdovinos, Tiffany Chang

Dartmouth Scholarship

Sonic hedgehog (Shh) and components of its signalling pathway have been identified in human prostate carcinoma and increased levels of their expression appear to correlate with disease progression and metastasis. The mechanism through which Shh signalling could promote metastasis in bone, the most common site for prostate carcinoma metastasis, has not yet been investigated. The present study determined the effect of Shh signalling between prostate cancer cells and pre-osteoblasts on osteoblast differentiation, a requisite process for new bone formation that characterizes prostate carcinoma metastasis.

Life Expectancy And Years Of Life Lost In Chronic Obstructive Pulmonary Disease: Findings From The Nhanes Iii Follow-Up Study, Robert M. Shavelle, David R. Paculdo, Scott J. Kush, David M. Mannino, David J. Strauss

Internal Medicine Faculty Publications

RATIONALE: Previous studies have demonstrated that chronic obstructive pulmonary disease (COPD) causes increased mortality in the general population. But life expectancy and the years of life lost have not been reported.

OBJECTIVES: To quantify mortality, examine how it varies with age, sex, and other risk factors, and determine how life expectancy is affected.

METHODS: We constructed mortality models using the Third National Health and Nutrition Examination Survey, adjusting for age, sex, race, and major medical conditions. We used these to compute life expectancy and the years of life lost.

MEASUREMENTS AND MAIN RESULTS: Pulmonary function testing classified patients as having …

Trends In Mental Health Of An Adolescent Medicine Clinic Patient Population, Abdel Salous, Linah Al-Alem, Hatim A. Omar

Pediatrics Faculty Publications

The correlation between exposure to forms of violence and development of mental disorders in victims is well established. The purpose of this paper was to identify mental health problems in an adolescent medicine clinic population in Lexington, KY and to investigate potential correlation of mental disorders with psychosocial factors. Data were gathered from the charts of 169 adolescent clinic patients (age 10-22) seen in the clinic for mental health care and analyzed using Excel. Of the patient population, 68% were urban, whereas 32% were rural. In terms of gender, 40% of the patients were male and 60% were female, 80% …

Discovering The Complexities Of Adolescent Compliance To Treatment, Megan Song, Hatim A. Omar

Pediatrics Faculty Publications

To explore the challenges faced in enhancing adolescent treatment compliance and to understand the roles of key players in this endeavor: the adolescent, parent and healthcare provider. Obtaining compliance from adolescents requires collaboration from the adolescent, caregiver and provider and depends on well-established relationships between each person in the triad: adolescent-provider, adolescent-caregiver, and caregiver-provider. Ensuring and improving adherence to treatment by adolescents is a challenging task but crucial to overall health outcomes. It requires the collaboration of the adolescent, parent and physician to create the optimal treatment plan, specifically tailored to the adolescent. For the clinician, maintaining good communication and …

Antibiotic Resistance In Staphylococcus Aureus-Containing Cutaneous Abscesses Of Patients With Hiv, Gus W Krucke, Deanna E Grimes, Richard M Grimes, Thai D Dang

Faculty, Staff and Student Publications

PURPOSE: The aim of this study was to document the resistance patterns found in exudates from cutaneous abscesses of HIV-infected persons.

BASIC PROCEDURES: Patient records were reviewed on 93 culture and sensitivity tests performed on exudates taken from incised and drained abscesses of HIV-infected persons.

MAIN FINDINGS: Of the specimens, 84.6% were Staphylococcus aureus. Of these, 93.5% were penicillin resistant, 87% oxacillin resistant, 84.4% cephazolin resistant, 84.4% erythromycin resistant, 52.2% ciprofloxacin resistant, and 15.6% tetracycline resistant. Fifty-eight specimens were tested for clindamycin with 29.3% found resistant; 85.7% were methicillin-resistant S aureus (MRSA) (defined as resistant to both penicillin G and …

Lymphocyte Proliferation To Mycobacterial Antigens Is Detectable Across A Spectrum Of Hiv-Associated Tuberculosis, Timothy Lahey, Mecky Matee, Lillian Mtei, Muhammad Bakari, Kisali Pallangyo, C Fordham Von Reyn

Dartmouth Scholarship

Background:

Identifying novel TB diagnostics is a major public health priority. We explored the diagnostic characteristics of antimycobacterial lymphocyte proliferation assays (LPA) in HIV-infected subjects with latent or active TB.

Methods:

HIV-infected subjects with bacille Calmette Guérin (BCG) scars and CD4 counts ≥ 200 cells/mm³ entering a TB booster vaccine trial in Tanzania had baseline in vivo and in vitro immune tests performed: tuberculin skin tests (TST), LPA and five day assays of interferon gamma (IFN-γ) release. Assay antigens were early secreted antigenic target 6 (ESAT-6), antigen 85 (Ag85), and Mycobacterium tuberculosis whole cell lysate (WCL). Subjects were screened …

Association Of Gucy2c Expression In Lymph Nodes With Time To Recurrence And Disease-Free Survival In Pn0 Colorectal Cancer., Scott A Waldman, Terry Hyslop, Stephanie Schulz, Alan Barkun, Karl Nielsen, Janis Haaf, Christine Bonaccorso, Yanyan Li, David S Weinberg

Department of Pharmacology and Experimental Therapeutics Faculty Papers

CONTEXT: The established relationship between lymph node metastasis and prognosis in colorectal cancer suggests that recurrence in 25% of patients with lymph nodes free of tumor cells by histopathology (pN0) reflects the presence of occult metastases. Guanylyl cyclase 2C (GUCY2C) is a marker expressed by colorectal tumors that could reveal occult metastases in lymph nodes and better estimate recurrence risk.

OBJECTIVE: To examine the association of occult lymph node metastases detected by quantifying GUCY2C messenger RNA, using the reverse transcriptase-polymerase chain reaction, with recurrence and survival in patients with colorectal cancer.

DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 257 patients …

Dna Instability In Replicating Huntington's Disease Lymphoblasts, Milena Cannella, Vittorio Maglione, Tiziana Martino, Giuseppe Ragona, Luigi Frati, Guo-Min Li, Ferdinando Squitieri

Toxicology and Cancer Biology Faculty Publications

BACKGROUND: The expanded CAG repeat in the Huntington's disease (HD) gene may display tissue-specific variability (e.g. triplet mosaicism) in repeat length, the longest mutations involving mitotic (germ and glial cells) and postmitotic (neurons) cells. What contributes to the triplet mutability underlying the development of HD nevertheless remains unknown. We investigated whether, besides the increased DNA instability documented in postmitotic neurons, possible environmental and genetic mechanisms, related to cell replication, may concur to determine CAG repeat mutability. To test this hypothesis we used, as a model, cultured HD patients' lymphoblasts with various CAG repeat lengths.

RESULTS: Although most lymphoblastoid cell lines …

Facilitated Monocyte-Macrophage Uptake And Tissue Distribution Of Superparmagnetic Iron-Oxide Nanoparticles., Arnaud Beduneau, Zhiya Ma, Cassi B. Grotepas, Alexander Kabanov, Barrett E. Rabinow, Nan Gong, R. Lee Mosley, Huanyu Dou, Michael D. Boska, Howard Gendelman

Journal Articles: Radiology

BACKGROUND: We posit that the same mononuclear phagocytes (MP) that serve as target cells and vehicles for a host of microbial infections can be used to improve diagnostics and drug delivery. We also theorize that physical and biological processes such as particle shape, size, coating and opsonization that affect MP clearance of debris and microbes can be harnessed to facilitate uptake of nanoparticles (NP) and tissue delivery.

METHODS: Monocytes and monocyte-derived macrophages (MDM) were used as vehicles of superparamagnetic iron oxide (SPIO) NP and immunoglobulin (IgG) or albumin coated SPIO for studies of uptake and distribution. IgG coated SPIO was …

Remission And Recovery In The Treatment For Adolescents With Depression Study (Tads): Acute And Long-Term Outcomes., Betsy D. Kennard, Susan G. Silva, Simon Tonev, Paul Rohde, Jennifer L. Hughes, Benedetto Vitiello, Christopher J. Kratochvil, John F. Curry, Graham J. Emslie, Mark Reinecke, John March

Journal Articles: Psychiatry

OBJECTIVE: We examine remission rate probabilities, recovery rates, and residual symptoms across 36 weeks in the Treatment for Adolescents with Depression Study (TADS).

METHOD: The TADS, a multisite clinical trial, randomized 439 adolescents with major depressive disorder to 12 weeks of treatment with fluoxetine, cognitive-behavioral therapy, their combination, or pill placebo. The pill placebo group, treated openly after week 12, was not included in the subsequent analyses. Treatment differences in remission rates and probabilities of remission over time are compared. Recovery rates in remitters at weeks 12 (acute phase remitters) and 18 (continuation phase remitters) are summarized. We also examined …

Atorvastatin May Have No Effect On Acute Phase Reaction In Children After Intravenous Bisphosphonate Infusion., Tarak Srivastava, Connie J. Haney, Uri S. Alon

Manuscripts, Articles, Book Chapters and Other Papers

Intravenous bisphosphonate therapy is associated with acute phase reaction characterized by fever and musculoskeletal pain. Bisphosphonates have been shown in vitro to activate gammadeltaT-cells to proliferate and produce cytokines, suggesting a role in acute phase reaction, which can be effectively blocked by statins. We conducted a double-blind randomized crossover placebo controlled study in 12 children (12.1 +/- 4.2 yr; 10 girls and 2 boys) receiving intravenous bisphosphonates to evaluate whether statins can be used to prevent acute phase reaction associated with therapy. Children received two cycles given 3-4 mo apart of intravenous bisphosphonate given on 2 consecutive days in each …

Multiple Independent Genetic Factors At Nos1ap Modulate The Qt Interval In A Multi-Ethnic Population, Dan E. Arking, Amit Khera, Chao Xing, W H Linda Kao, Wendy Post, Eric Boerwinkle, Aravinda Chakravarti

Faculty, Staff and Student Publications

Extremes of electrocardiographic QT interval are associated with increased risk for sudden cardiac death (SCD); thus, identification and characterization of genetic variants that modulate QT interval may elucidate the underlying etiology of SCD. Previous studies have revealed an association between a common genetic variant in NOS1AP and QT interval in populations of European ancestry, but this finding has not been extended to other ethnic populations. We sought to characterize the effects of NOS1AP genetic variants on QT interval in the multi-ethnic population-based Dallas Heart Study (DHS, n = 3,072). The SNP most strongly associated with QT interval in previous samples …

Mitostatin, A Putative Tumor Suppressor On Chromosome 12q24.1, Is Downregulated In Human Bladder And Breast Cancer., A Vecchione, M Fassan, V Anesti, A Morrione, S Goldoni, G Baldassarre, D Byrne, D D'Arca, J P Palazzo, J Lloyd, L Scorrano, L G Gomella, R V Iozzo, R Baffa

Department of Urology Faculty Papers

Allelic deletions on human chromosome 12q24 are frequently reported in a variety of malignant neoplasms, indicating the presence of a tumor suppressor gene(s) in this chromosomal region. However, no reasonable candidate has been identified so far. In this study, we report the cloning and functional characterization of a novel mitochondrial protein with tumor suppressor activity, henceforth designated MITOSTATIN. Human MITOSTATIN was found within a 3.2-kb transcript, which encoded a approximately 62 kDa, ubiquitously expressed protein with little homology to any known protein. We found homozygous deletions and mutations of MITOSTATIN gene in approximately 5 and approximately 11% of various cancer-derived …

Genetic And Hormonal Factors Modulate Spreading Depression And Transient Hemiparesis In Mouse Models Of Familial Hemiplegic Migraine Type 1, Katharina Eikermann-Haerter, Ergin Dileköz, Chiho Kudo, Sean I Savitz, Christian Waeber, Michael J Baum, Michel D Ferrari, Arn M J M Van Den Maagdenberg, Michael A Moskowitz, Cenk Ayata

Faculty, Staff and Student Publications

Familial hemiplegic migraine type 1 (FHM1) is an autosomal dominant subtype of migraine with aura that is associated with hemiparesis. As with other types of migraine, it affects women more frequently than men. FHM1 is caused by mutations in the CACNA1A gene, which encodes the alpha1A subunit of Cav2.1 channels; the R192Q mutation in CACNA1A causes a mild form of FHM1, whereas the S218L mutation causes a severe, often lethal phenotype. Spreading depression (SD), a slowly propagating neuronal and glial cell depolarization that leads to depression of neuronal activity, is the most likely cause of migraine aura. Here, we have …

Aging And Endothelial Progenitor Cell Telomere Length In Healthy Men, Erich J Kushner, Gary Van Guilder, Owen J Maceneaney, Jennifer N Cech, Brian L Stauffer, Christopher A Desouza

Health and Nutritional Sciences Faculty Publications

BACKGROUND: Telomere length declines with age in mature endothelial cells and is thought to contribute to endothelial dysfunction and atherogenesis. Bone marrow-derived circulating endothelial progenitor cells (EPCs) are critical to vascular health as they contribute to both reendothelialization and neovascularization. We tested the hypothesis that EPC telomere length decreases with age in healthy adult humans.
METHODS: Peripheral blood samples were collected from 40 healthy, non-obese, sedentary men: 12 young (age 21-34 years), 12 middle-aged (43-55 years) and 16 older (57-68 years). Putative EPCs were isolated from peripheral blood mononuclear cells and telomere length was determined using genomic DNA preparation and …

Activity Loss Is Associated With Cognitive Decline In Age-Related Macular Degeneration., Barry W. Rovner, Robin J. Casten, Benjamin E. Leiby, William S. Tasman

Department of Psychiatry and Human Behavior Faculty Papers

BACKGROUND/METHODS: The objective of this study was to determine whether relinquishing cognitive, physical, and social activities is associated with an increased risk of cognitive decline in patients with age-related macular degeneration (AMD). We conducted a 3-year longitudinal study of 206 nondemented patients with AMD.

RESULTS: Twenty-three subjects (14.4%) declined cognitively. Age, sex, education, decline in visual acuity, and number of dropped activities were associated with cognitive decline; each additional dropped activity increased the risk by 58%. Subjects who relinquished three activities were 3.87 times (95% confidence interval, 1.95-7.76) more likely to become demented than subjects who relinquished no activities; those …

Unusual Fibrosclerotic Lesion Of The Laryngotracheal Complex Presenting As Subglottic Stenosis., Douglas R. Johnston, Joseph M. Curry, Raphael Rubin, Marc R. Rosen

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

We present a case report that describes the pathology, presentation, and management complexities of an unusual, destructive fibrosclerotic lesion of the laryngotracheal complex. An otherwise healthy 21-year-old man presented with a 1-year history of progressive shortness of breath and stridor. The initial examination revealed a 3-cm, grade III subglottic stenosis. Nodular fibrosis of the strap muscles, laryngotracheal cartilages, and trachea was evident. Biopsies revealed dense peritracheal desmoplastic reaction with focal erosion of cartilage. However, features diagnostic for relapsing polychondritis, desmoid tumor, or orbital pseudotumor were absent. The disease progressed to involve severe stenosis and thickening of the trachea and main …

Malignant Melanoma Metastatic To The Thyroid Gland: A Case Report And Review Of The Literature., Brian Kung, Md, Saba Aftab, Bs, Moira D. Wood, Md, David Rosen, Md

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

The thyroid gland is a relatively uncommon site for a secondary malignancy; even less common is a case of malignant melanoma metastatic to the thyroid. We describe the case of a 68-year-old man who presented with a neck mass in the posterior triangle. Fine-needle aspiration biopsy (FNAB) identified the mass as a malignant melanoma. The patient had had no known primary skin melanoma. He underwent a left modified radical neck dissection, and the mass was discovered to be a positive lymph node. Postoperatively, he declined to undergo radio- and chemotherapy. Eighteen months later, he returned with a diffusely enlarged thyroid. …

Microrna Expression Profiling Of Male Breast Cancer., Matteo Fassan, Raffaele Baffa, Juan P Palazzo, Joshua Lloyd, Marco Crosariol, Chang-Gong Liu, Stefano Volinia, Hannes Alder, Massimo Rugge, Carlo M Croce, Anne Rosenberg

Department of Urology Faculty Papers

INTRODUCTION : MicroRNAs (miRNAs) are a class of small noncoding RNAs that control gene expression by targeting mRNAs and triggering either translation repression or RNA degradation. Their aberrant expression may be involved in human diseases, including cancer. To test the hypothesis that there is a specific miRNA expression signature which characterizes male breast cancers, we performed miRNA microarray analysis in a series of male breast cancers and compared them with cases of male gynecomastia and female breast cancers. METHODS : Paraffin blocks were obtained at the Department of Pathology of Thomas Jefferson University from 28 male patients including 23 breast …

A Glycosylated Recombinant Human Granulocyte Colony Stimulating Factor Produced In A Novel Protein Production System (Avi-014) In Healthy Subjects: A First-In Human, Single Dose, Controlled Study., Roslyn Varki, Ed Pequignot, Mark C Leavitt, Andres Ferber, Walter K Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND: AVI-014 is an egg white-derived, recombinant, human granulocyte colony-stimulating factor (G-CSF). This healthy volunteer study is the first human investigation of AVI-014. METHODS: 24 male and female subjects received a single subcutaneous injection of AVI-014 at 4 or 8 mcg/kg. 16 control subjects received 4 or 8 mcg/kg of filgrastim (Neupogen, Amgen) in a partially blinded, parallel fashion. RESULTS: The Geometric Mean Ratio (GMR) (90% CI) of 4 mcg/kg AVI-014/filgrastim AUC(0-72 hr) was 1.00 (0.76, 1.31) and Cmax was 0.86 (0.66, 1.13). At the 8 mcg/kg dose, the AUC(0-72) GMR was 0.89 (0.69, 1.14) and Cmax was 0.76 (0.58, …

Hematologic Effects Of Placental Pathology On Very Low Birthweight Infants Born To Mothers With Preeclampsia., Kelly J. Zook, Md, Amy B. Mackley, Rnc, Jennifer Kern, David A. Paul. Md

Department of Pediatrics Faculty Papers

OBJECTIVE: To investigate the effect of placental pathology on neonatal neutrophils, platelets, hematocrit and nucleated red blood cells in very low birthweight (VLBW) infants born to mothers with preeclampsia. STUDY DESIGN: Retrospective cohort study of infants with birthweight < 1500 g born to mothers with preeclampsia from july, 2002 to july, 2006 at a single level III neonatal intensive care unit. Placental pathology was reviewed for the presence of placental infarction and vasculopathy. Hematologic parameters from day of life 0, 1 and 2 were obtained. Statistical analysis included repeated-measures analysis of variance and multivariable analysis using logistic regression. RESULT: The study sample included 203 infants with estimated gestational age of 28+/-3 weeks; 45% had placental infarctions and 26% placental vasculopathy. Infants with neutropenia and thrombocytopenia did not have an increased occurrence of placental infarction or maternal vasculopathy but were more likely to be of small gestational age (SGA) and of lower gestational age compared with infants without neutropenia or thrombocytopenia. After multivariable analysis, gestational age and SGA remained associated with both neutropenia and thrombocytopenia whereas placental infarction and vasculopathy did not remain in the models. CONCLUSION: In our population of VLBW infants born to mothers with preeclampsia, placental pathology was common. There was no association of placental infarction or vasculopathy with neonatal neutropenia and thrombocytopenia. The data suggest that neonatal hematologic effects of maternal preeclampsia, if related to the placenta, are associated with factors other than placental histology.

Elevated Expression Of L-Selectin Ligand In Lymph Node-Derived Human Prostate Cancer Cells Correlates With Increased Tumorigenicity., Prakash Radhakrishnan, Ming-Fong Lin, Pi-Wan Cheng

Journal Articles: Biochemistry & Molecular Biology

Human prostate cancer LNCaP cells including C-33 and C-81 cells were originally derived from the lymph nodes of a patient with metastatic prostate cancer. These two cells were employed for characterization of L-selectin ligand and in vitro tumorigenicity, because they mimic the clinical conditions of early and late-stage human prostate cancer. C-81 cells exhibit higher in vitro migratory and invasive properties as compared with C-33 cells. We find that the L-selectin ligand and mucin glycan-associated MECA-79 epitope were elevated in C-81 cells. An increase of these glycotopes positively correlates with elevated tumorigenicity and expression of key glycosyl- and sulfotransferase genes. …

Functional Interleukin-17 Receptor A Is Expressed In Central Nervous System Glia And Upregulated In Experimental Autoimmune Encephalomyelitis., Jayasri Das Sarma, Bogoljub Ciric, Ryan Marek, Sanjoy Sadhukhan, Michael L. Caruso, Jasmine Shafagh, Denise C. Fitzgerald, Kenneth S. Shindler, Am Rostami

Department of Neurology Faculty Papers

BACKGROUND: Interleukin-17A (IL-17A) is the founding member of a novel family of inflammatory cytokines that plays a critical role in the pathogenesis of many autoimmune diseases, including multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). IL-17A signals through its receptor, IL-17RA, which is expressed in many peripheral tissues; however, expression of IL-17RA in the central nervous system (CNS) and its role in CNS inflammation are not well understood.

METHODS: EAE was induced in C57Bl/6 mice by immunization with myelin oligodendroglial glycoprotein. IL-17RA expression in the CNS was compared between control and EAE mice using RT-PCR, in situ …

Revealing Genes Associated With Vitellogenesis In The Liver Of The Zebrafish (Danio Rerio) By Transcriptome Profiling., Liraz Levi, Irena Pekarski, Ellen Gutman, Paolo Fortina, Terry Hyslop, Jakob Biran, Berta Levavi-Sivan, Esther Lubzens

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: In oviparous vertebrates, including fish, vitellogenesis consists of highly regulated pathways involving 17beta-estradiol (E2). Previous studies focused on a relatively small number of hepatic expressed genes during vitellogenesis. This study aims to identify hepatic genes involved in vitellogenesis and regulated by E2, by using zebrafish microarray gene expression profiling, and to provide information on functional distinctive genes expressed in the liver of a vitellogenic female, using zebrafish as a model fish. RESULTS: Genes associated with vitellogenesis were revealed by the following paired t-tests (SAM) comparisons: a) two-month old vitellogenic (Vit2) females were compared with non-vitellogenic (NV) females, showing 825 …

Reduced Neutrophil Count In People Of African Descent Is Due To A Regulatory Variant In The Duffy Antigen Receptor For Chemokines Gene, David Reich, Michael A. Nalls, W H Linda Kao, Ermeg L. Akylbekova, Arti Tandon, Nick Patterson, James Mullikin, Wen-Chi Hsueh, Ching-Yu Cheng, Josef Coresh, Eric Boerwinkle, Man Li, Alicja Waliszewska, Julie Neubauer, Rongling Li, Tennille S. Leak, Lynette Ekunwe, Joe C. Files, Cheryl L. Hardy, Joseph M. Zmuda, Herman A. Taylor, Elad Ziv, Tamara B. Harris, James G. Wilson

Faculty, Staff and Student Publications

Persistently low white blood cell count (WBC) and neutrophil count is a well-described phenomenon in persons of African ancestry, whose etiology remains unknown. We recently used admixture mapping to identify an approximately 1-megabase region on chromosome 1, where ancestry status (African or European) almost entirely accounted for the difference in WBC between African Americans and European Americans. to identify the specific genetic change responsible for this association, we analyzed genotype and phenotype data from 6,005 African Americans from the Jackson Heart Study (JHS), the Health, Aging and Body Composition (Health ABC) Study, and the Atherosclerosis Risk in Communities (ARIC) Study. …