Medical Molecular Biology Commons^™

Autoimmunity To Vimentin And Lupus Nephritis, A. Davidson

Journal Articles

No abstract provided.

Letter From Incoming Editor In Chief Of Molecular Medicine, Dr. Betty Diamond, B. Diamond

Journal Articles

No abstract provided.

Low-Dose T-3 Replacement Restores Depressed Cardiac T-3 Levels, Preserves Coronary Microvasculature And Attenuates Cardiac Dysfunction In Experimental Diabetes Mellitus, N. Y. Weltman, K. Ojamaa, E. H. Schlenker, Y. F. Chen, R. Zucchi, A. Saba, D. Colligiani, V. Rajagopalan, C. J. Pol, A. M. Gerdes

Journal Articles

Thyroid dysfunction is common in individuals with diabetes mellitus (DM) and may contribute to the associated cardiac dysfunction. However, little is known about the extent and pathophysiological consequences of low thyroid conditions on the heart in DM. DM was induced in adult female Sprague Dawley (SD) rats by injection of nicotinamide (N; 200 mg/kg) followed by streptozotocin (STZ; 65 mg/kg). One month after STZ/N, rats were randomized to the following groups (N = 10/group): STZ/N or STZ/N + 0.03 g/mL T-3; age-matched vehicle-treated rats served as nondiabetic controls (C). After 2 months of T-3 treatment (3 months post-DM induction), left …

Genotyping Of Immune-Related Genetic Variants Identifies Tyk2 As A Novel Associated Locus For Idiopathic Inflammatory Myopathies, M. Jani, J. Massey, L. R. Wedderburn, J. Vencovsky, K. Danko, I. E. Lundberg, L. Padyukov, A. Lee, P. K. Gregersen, Eumyonet, +10 Additional Authors

Journal Articles

No abstract provided.

Does A Glp-1 Receptor Agonist Change Glucose Tolerance In Patients Treated With Antipsychotic Medications? Design Of A Randomised, Double-Blinded, Placebo-Controlled Clinical Trial, J. R. Larsen, L. Vedtofte, J. J. Holst, P. Oturai, A. Kjaer, Christoph Correll, T. Vilsboll, A. Fink-Jensen

Journal Articles

Background Metabolic disturbances, obesity and life-shortening cardiovascular morbidity are major clinical problems among patients with antipsychotic treatment. Especially two of the most efficacious antipsychotics, clozapine and olanzapine, cause weight gain and metabolic disturbances. Additionally, patients with schizophrenia-spectrum disorders not infrequently consume alcohol. Glucagon-like peptide-1 (GLP-1) has shown to improve glycaemic control and reduce alcohol intake among patients with type 2 diabetes. Objectives To investigate whether the beneficial effects of GLP-1 analogues on glycaemic control and alcohol intake, in patients with type 2 diabetes, can be extended to a population of pre-diabetic psychiatric patients receiving antipsychotic treatment. Methods and analysis Trial …

Quetiapine Versus Aripiprazole In Children And Adolescents With Psychosis - Protocol For The Randomised, Blinded Clinical Tolerability And Efficacy Of Antipsychotics (Tea) Trial, A. K. Pagsberg, P. Jeppesen, D. G. Klauber, K. G. Jensen, D. Ruda, M. Stentebjerg-Olesen, P. Jantzen, S. Rasmussen, Christoph Correll, B. Fagerlund, +19 Additional Authors

Journal Articles

Background: The evidence for choices between antipsychotics for children and adolescents with schizophrenia and other psychotic disorders is limited. The main objective of the Tolerability and Efficacy of Antipsychotics (TEA) trial is to compare the benefits and harms of quetiapine versus aripiprazole in children and adolescents with psychosis in order to inform rational, effective and safe treatment selections. Methods/Design: The TEA trial is a Danish investigator-initiated, independently funded, multi-centre, randomised, blinded clinical trial. Based on sample size estimation, 112 patients aged 12-17 years with psychosis, antipsychotic-naive or treated for a limited period are, 1:1 randomised to a 12-week, double-blind intervention …

Sentia: A Systematic Online Monitoring Registry For Children And Adolescents Treated With Antipsychotics, I. Palanca-Maresca, B. Ruiz-Antoran, G. Centeno-Soto, S. Jimenez-Fernandez, L. Garcia-Murillo, A. Siles, S. Villagra, H. Blasco-Fontecilla, L. Iruela-Cuadrado, Christoph Correll, +2 Additional Authors

Journal Articles

INTRODUCTION: Despite drastic increases in antipsychotic prescribing in youth, data are still limited regarding their safety in this vulnerable population, necessitating additional tools for capturing long-term, real world data. METHODS: We present SENTIA (SafEty of NeurolepTics in Infancy and Adolescence; https://SENTIA.es), an online registry created in 2010 to track antipsychotic adverse effects in Spanish youthsociodemographic, diagnostic and treatment characteristics, past personal medical/psychiatric history, healthy lifestyle habits and treatment adherence. Additionally, efficacy and adverse effect data are recorded including the Children's Global Assessment Scale; Clinical Global Impressions scale for Severity and Improvement, the Safety Monitoring Uniform Report Form, Simpson-Angus Scale, Abnormal …

Early Specific Cognitive-Behavioural Psychotherapy In Subjects At High Risk For Bipolar Disorders: Study Protocol For A Randomised Controlled Trial, A. Pfennig, K. Leopold, A. Bechdolf, C. U. Correll, M. Holtmann, M. Lambert, C. Marx, T. D. Meyer, G. Juckel, M. Bauer, +5 Additional Authors

Journal Articles

Background: Bipolar disorders (BD) are among the most severe mental disorders with first clinical signs and symptoms frequently appearing in adolescence and early adulthood. The long latency in clinical diagnosis (and subsequent adequate treatment) adversely affects the course of disease, effectiveness of interventions and health-related quality of life, and increases the economic burden of BD. Despite uncertainties about risk constellations and symptomatology in the early stages of potentially developing BD, many adolescents and young adults seek help, and most of them suffer substantially from symptoms already leading to impairments in psychosocial functioning in school, training, at work and in their …

Treatment Of Lupus Nephritis With Abatacept: The Abatacept And Cyclophosphamide Combination Efficacy And Safety Study, A. Askanase, M. Byron, L. Keyes-Elstein, P. Cagnoli, J. Mccune, B. Diamond, D. Daikh, A. Davidson, M. Mackay, D. Wofsy, +24 Additional Authors

Journal Articles

OBJECTIVE: To assess the efficacy and safety of a 24-week course of abatacept in the treatment of active lupus nephritis and to assess the potential of abatacept to induce "clinical tolerance," defined as sustained clinical quiescence of lupus nephritis after discontinuation of immunosuppressive therapy. METHODS: Patients with active lupus nephritis (n = 134) were enrolled in a randomized, double-blind phase II add-on trial in which they received either abatacept or placebo in conjunction with the Euro-Lupus Nephritis Trial regimen of low-dose cyclophosphamide (CYC) followed by azathioprine (AZA). The primary efficacy outcome was the frequency of complete response at week 24. …

Robotic Measurement Of Arm Movements After Stroke Establishes Biomarkers Of Motor Recovery, H. I. Krebs, M. Krams, D. K. Agrafiotis, A. Dibernardo, J. C. Chavez, G. S. Littman, E. Yang, G. Byttebier, L. Dipietro, B. T. Volpe, +4 Additional Authors

Journal Articles

Background and Purpose Because robotic devices record the kinematics and kinetics of human movements with high resolution, we hypothesized that robotic measures collected longitudinally in patients after stroke would bear a significant relationship to standard clinical outcome measures and, therefore, might provide superior biomarkers. Methods In patients with moderate-to-severe acute ischemic stroke, we used clinical scales and robotic devices to measure arm movement 7, 14, 21, 30, and 90 days after the event at 2 clinical sites. The robots are interactive devices that measure speed, position, and force so that calculated kinematic and kinetic parameters could be compared with clinical …

Radiation Absorbed Dose To The Basal Ganglia From Dopamine Transporter Radioligand F-18-Fpcit, W. Robeson, V. Dhawan, Y. L. Ma, D. Bjelke, C. Margouleff, T. Chaly, D. Eidelberg

Journal Articles

Our previous dosimetry studies have demonstrated that for dopaminergic radiotracers, F-18-FDOPA and F-18-FPCIT, the urinary bladder is the critical organ. As these tracers accumulate in the basal ganglia (BG) with high affinity and long residence times, radiation dose to the BG may become significant, especially in normal control subjects. We have performed dynamic PET measurements using F-18-FPCIT in 16 normal adult subjects to determine if in fact the BG, although not a whole organ, but a well-defined substructure, receives the highest dose. Regions of interest were drawn over left and right BG structures. Resultant time-activity curves were generated and used …

Integrating Phage Therapy Into Western Medicine, Jacob B. Jaminet

UROP Posters

The World Health Organization has described the rise of antibiotic use as a “global heath security emergency” (who.int). With the growing concern about antibiotic resistant bacteria, there has been an increased interest in bacteriophages. Bacteriophages are high-specific viruses that only infect bacteria. The use of bacteriophages medicinally to treat bacteria is called phage therapy. Research in phage therapy gained momentum until the introduction of antibiotics. While the USA and other Western countries accepted antibiotics, the Soviet Union and their satellite nations still continued to research phages. Since the funding for research was supplied by the Soviet military, the results of …

Altered Mucins (Muc) Trafficking In Benign And Malignant Conditions., Suhasini Joshi, Sushil Kumar, Amit Choudhury, Moorthy P. Ponnusamy, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Mucins are high molecular weight O-glycoproteins that are predominantly expressed at the apical surface of epithelial cells and have wide range of functions. The functional diversity is attributed to their structure that comprises of a peptide chain with unique domains and multiple carbohydrate moieties added during posttranslational modifications. Tumor cells aberrantly overexpress mucins, and thereby promote proliferation, differentiation, motility, invasion and metastasis. Along with their aberrant expression, accumulating evidence suggest the critical role of altered subcellular localization of mucins under pathological conditions due to altered endocytic processes. The mislocalization of mucins and their interactions result in change in the density …

Expression And Splicing Of Alzheimer’S Disease Risk Gene Phosphatidylinositol-Binding Clathrin Assembly Protein, Ishita Parikh

Theses and Dissertations--Physiology

Recent Genome Wide Association Studies (GWAS) have identified a series of single nucleotide polymorphism (SNP)s that are associated with Alzheimer’s disease (AD). One of the SNPs, rs3851179 (G/A), is near the gene phosphatidylinositol-binding clathrin assembly protein (PICALM). To evaluate whether this SNP is associated with PICALM expression, we quantified PICALM mRNA in 56 brain cDNA samples. Using linear regression analysis, we analyzed PICALM expression relative to rs3851179, AD status, and cell type specific markers. An association was detected between rs3851179 and PICALM, microvessel mRNA, glial fibrillary acidic protein (GFAP) mRNA, and synaptophysin (SYN) mRNA. To gain clarity …

Inhibition Of Rac1 Gtpase Sensitizes Pancreatic Cancer Cells To Γ-Irradiation, Y Yan, Ashley L. Hein, Asserewou Etekpo, Katrina M. Burchett, Chi Lin, Charles A. Enke, Surinder K. Batra, Kenneth Cowan, Michel M. Ouellette

Journal Articles: Biochemistry & Molecular Biology

Radiation therapy is a staple treatment for pancreatic cancer. However, owing to the intrinsic radioresistance of pancreatic cancer cells, radiation therapy often fails to increase survival of pancreatic cancer patients. Radiation impedes cancer cells by inducing DNA damage, which can activate cell cycle checkpoints. Normal cells possess both a G1 and G2 checkpoint. However, cancer cells are often defective in G1 checkpoint due to mutations/alterations in key regulators of this checkpoint. Accordingly, our results show that normal pancreatic ductal cells respond to ionizing radiation (IR) with activation of both checkpoints whereas pancreatic cancer cells respond to IR with G2/M arrest …

Analysis Of The Role Of Astrocyte Elevated Gene-1 In Normal Liver Physiology And In The Onset And Progression Of Hepatocellular Carcinoma, Chadia L. Robertson

Theses and Dissertations

First identified over a decade ago, Astrocyte Elevated Gene-1 (AEG-1) has been studied extensively due to early reports of its overexpression in various cancer cell lines. Research groups all over the globe including our own have since identified AEG-1 overexpression in cancers of diverse lineages including cancers of the liver, colon, skin, prostate, breast, lung, esophagus, neurons and neuronal glia as compared to matched normal tissue. A comprehensive and convincing body of data currently points to AEG-1 as an essential component, critical to the progression and perhaps onset of cancer. AEG-1 is a potent activator of multiple pro-tumorigenic signal transduction …

A Study Of Functional Recovery And Axonal Plasticity Following Tbi And Anti-Nogo-A Immunotherapy, Jennifer Crystal Biesiadecki

Master's Theses

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality globally and often results in long term disability. Unfortunately, the success of rehabilitation techniques as therapy for TBI is limited, which may be due to the growth restrictive environment of the adult central nervous system (CNS). This environment is thought to result from glial scars, lack of neurotrophic factors, and the presence of an array of growth-inhibitory molecules. One such growth-inhibitory molecule is the protein Nogo-A. Our laboratory has shown that neutralization of Nogo-A with anti-Nogo-A immunotherapy after ischemic stroke results in improvement in functional recovery in the …

Inflammatory Cytokine Gene Expression In Mesenteric Adipose Tissue During Acute Experimental Colitis, William Conan Mustain, Marlene E. Starr, Joseph Daniel Valentino, Donald A. Cohen, Daiki Okamura, Chi Wang, B. Mark Evers, Hiroshi Saito

Markey Cancer Center Faculty Publications

BACKGROUND: Production of inflammatory cytokines by mesenteric adipose tissue (MAT) has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Animal models of colitis have demonstrated inflammatory changes within MAT, but it is unclear if these changes occur in isolation or as part of a systemic adipose tissue response. It is also unknown what cell types are responsible for cytokine production within MAT. The present study was designed to determine whether cytokine production by MAT during experimental colitis is depot-specific, and also to identify the source of cytokine production within MAT.

METHODS: Experimental colitis was induced in 6-month-old C57BL/6 …

Impact Of Noise On Molecular Network Inference, Radhakrishnan Nagarajan, Marco Scutari

Biostatistics Faculty Publications

Molecular entities work in concert as a system and mediate phenotypic outcomes and disease states. There has been recent interest in modelling the associations between molecular entities from their observed expression profiles as networks using a battery of algorithms. These networks have proven to be useful abstractions of the underlying pathways and signalling mechanisms. Noise is ubiquitous in molecular data and can have a pronounced effect on the inferred network. Noise can be an outcome of several factors including: inherent stochastic mechanisms at the molecular level, variation in the abundance of molecules, heterogeneity, sensitivity of the biological assay or measurement …

Development Of Novel Antifungal Peptides Based On A Natural Model Of Histatin-5 Peptide, Duy Tu Nguyen

Graduate Theses and Dissertations

Our research group is working toward the development of novel antifungal peptides based on a natural model of peptide histatin-5. Histatin-5 is found in human saliva and known to protect our body against oral infections by Candida species. Candidiasis, or an infection caused by Candida species, is considered one of the most medically important fungal infections worldwide. Blood stream infections caused by Candida species are the fourth leading cause of hospital-acquired fungal infections that is associated with high mortality rates and high costs of treatment. This study investigated the modes of action of histatin-5 with the use of one 16-mer …