Diseases Commons^™

Interventions To Reduce Neonatal Mortality From Neonatal Tetanus In Low And Middle Income Countries - A Systematic Review, Adeel Ahmed Khan, Aysha Zahidie, F. Rabbani

Community Health Sciences

Background

In 1988, WHO estimated around 787,000 newborns deaths due to neonatal tetanus. Despite few success stories majority of the Low and Middle Income Countries (LMICs) are still struggling to reduce neonatal mortality due to neonatal tetanus. We conducted a systematic review to understand the interventions that have had a substantial effect on reducing neonatal mortality rate due to neonatal tetanus in LMICs and come up with feasible recommendations for decreasing neonatal tetanus in the Pakistani setting.

Methods

We systemically reviewed the published literature (Pubmed and Pubget databases) to identify appropriate interventions for reducing tetanus related neonatal mortality. A total …

Fibromyalgia Syndrome: A Pathoneurological Basis Of Disease, Alex D. Hamilton

Senior Honors Theses

Fibromyalgia (also known as fibromyalgia syndrome, or FMS) is a condition which causes its victims to suffer a wide range of symptoms, most notably chronic musculoskeletal pain. Although the causes of fibromyalgia remain unknown, recent advances help elucidate the underlying pathophysiologies of this condition, and show that it is likely not a musculoskeletal condition, but rather a pathoneurological condition.

Cd4 And Cd8 T Cells Directly Recognize Murine Gammaherpesvirus 68-Immortalized Cells And Prevent Tumor Outgrowth, Xiaozhan Liang, Rebecca L. Crepeau, Weijun Zhang, Samuel H. Speck, Edward J. Usherwood

Dartmouth Scholarship

There has been extensive research regarding T cell recognition of Epstein-Barr virus-transformed cells; however, less is known regarding the recognition of B cells immortalized by gamma-2 herpesviruses. Here we show that B cells immortalized by murine gammaherpesvirus 68 (MHV-68, γHV-68) can be controlled by either CD4 or CD8 T cells in vivo. We present evidence for the direct recognition of infected B cells by CD4 and CD8 T cells. These data will help in the development of immunotherapeutic approaches combating gamma-2 herpesvirus-related disease.

Differential Effects Of Micrornas On Glioblastoma Growth And Migration, Duane Jeansonne, Marco Pacifici, Adam Lassak, Krzysztof Reiss, Giuseppe Russo, Jovanny Zabaleta, Francesca Peruzzi

School of Medicine Faculty Publications

Glioblastoma multiforme is characterized by rapid proliferation, aggressive metastatic potential, and resistance to radio- and chemotherapy. The matricellular protein CYR61 regulates cellular proliferation and migration and is highly expressed in Glioblastomas. MicroRNAs are 22-nucleotides long RNAs that regulate gene expression post-transcriptionally. Here, we utilized the LN229 glioblastoma cell line and found that CYR61 is a target of miR-136, miR-155, and miR-634. Over-expression of miR-136 and miR-634 miRNAs negatively affected proliferation, but not migration, while expression of miR-155 reduced migration but did not affect the proliferation of LN229 cells. Investigation of the molecular mechanisms affected by expression of miR-634 revealed an …

Break Out: Urogenital Schistosomiasis And Schistosoma Haematobium Infection In The Post-Genomic Era, Paul J. Brindley, Peter J. Hotez

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.

Icad Deficiency In Human Colon Cancer And Predisposition To Colon Tumorigenesis: Linkage To Apoptosis Resistance And Genomic Instability, Youssef Errami, Hassan Brim, Karine Oumouna-Benachour, Mustapha Oumouna, Amarjit S. Naura, Hogyoung Kim, Jihang Ju, Christian J. Davis, Jong G. Kim, Hassan Ashktorab, Kenneth Fallon, Ming Xu, Jianhua Zhang, Luis Del Valle, A Hamid Boulares

School of Medicine Faculty Publications

We previously showed that DNA fragmentation factor, which comprises a caspase-3-activated DNase (CAD) and its inhibitor (ICAD), may influence the rate of cell death by generating PARP-1-activating DNA breaks. Here we tested the hypothesis that ICAD-deficient colon epithelial cells exhibiting resistance to death stimuli may accumulate additional genetic modifications, leading to a tumorigenic phenotype. We show that ICAD deficiency may be associated with colon malignancy in humans. Indeed, an examination of ICAD expression using immunohistochemistry in an array of both colon cancer and normal tissues revealed that ICAD expression levels were severely compromised in the cancerous tissues. Upon DNA damage …

Diagnosis And Evaluation Of Peripheral Neuropathies, Jay D. Varrato Do

Neurology Update for the Non-Neurologist

No abstract provided.

Diagnosis And Treatment Options For Multiple Sclerosis, Gary Clauser Md

Neurology Update for the Non-Neurologist

No abstract provided.

Current Standards For Treatment Of Stroke: Management Of Acute Ischemic Stroke, John E. Castaldo Md

Neurology Update for the Non-Neurologist

No abstract provided.

Diagnosis, Evaluation And Treatments For Dementia, John W. Margraf Md

Neurology Update for the Non-Neurologist

No abstract provided.

Treatment Options For Seizures: Practical Points In Epilepsy Management, Soraya E. Jiménez Md

Neurology Update for the Non-Neurologist

No abstract provided.

Diagnosis, Assessment And Evaluation For Seizures, John W. Margraf Md

Neurology Update for the Non-Neurologist

No abstract provided.

Special Populations And Considerations In Migraine Therapy, Gary Clauser Md

Neurology Update for the Non-Neurologist

No abstract provided.

Migraine Diagnosis And Treatment, Vitaliy Koss Md

Neurology Update for the Non-Neurologist

No abstract provided.

Defining The Need For Specific Neurological Studies, John E. Castaldo Md

Neurology Update for the Non-Neurologist

No abstract provided.

Data Mining The Functional Characterizations Of Proteins To Predict Their Cancer-Relatedness, Peter Revesz, Christopher Assi

School of Computing: Faculty Publications

This paper considers two types of protein data. First, data about protein function described in a number of ways, such as, GO terms and PFAM families. Second, data about whether individual proteins are experimentally associated with cancer by an anomalous elevation or lowering of their expressions within cancerous cells. We combine these two types of protein data and test whether the first type of data, that is, the functional descriptors, can predict the second type of data, that is, cancer-relatedness. By using data mining and machine learning, we derive a classifier algorithm that using only GO term and PFAM family …

Development Of A Diagnostic Test Set To Assess Agreement In Breast Pathology: Practical Application Of The Guidelines For Reporting Reliability And Agreement Studies (Grras), Natalia V. Oster, Patricia A. Carney, Kimberly H. Allison, Donald L. Weaver, Lisa Reisch, Gary Longton, Tracy Onega

Dartmouth Scholarship

Diagnostic test sets are a valuable research tool that contributes importantly to the validity and reliability of studies that assess agreement in breast pathology. In order to fully understand the strengths and weaknesses of any agreement and reliability study, however, the methods should be fully reported. In this paper we provide a step-by-step description of the methods used to create four complex test sets for a study of diagnostic agreement among pathologists interpreting breast biopsy specimens. We use the newly developed Guidelines for Reporting Reliability and Agreement Studies (GRRAS) as a basis to report these methods.

Effects Of Treatment On Ige Responses Against Parasite Allergen-Like Proteins And Immunit To Reinfection In Childhood Schistosome And Hookworm Coinfections, Angela Pinot De Moira, Frances M. Jones, Shona Wilson, Edridah Tukahebwa, Colin M. Fitzsimmons, Joseph K. Mwatha, Jeffrey M. Bethony, Narcis B. Kabatereine, David W. Dunne

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Naturally occurring human immunity to both schistosomiasis and hookworm infection has been associated with IgE responses against parasite allergen-like proteins. Since the two helminths frequently coinfect the same individuals, there is growing advocacy for their concurrent treatment. However, both helminths are known to exert strong immunomodulatory effects; therefore, coinfected individuals could have immune responses different from those characteristically seen in monoinfected individuals. In this study, we measured changes in IgE, IgG1, and IgG4 responses to schistosome and hookworm antigens, including the allergen-like proteins Schistosoma mansoni tegumental-allergen-like 1 protein (SmTAL1), SmTAL2, and Necator americanus Ancylostoma-secreted protein-2 (Na-ASP-2), following concurrent …

Transcriptional Responses Of In Vivo Praziquantel Exposure In Schistosomes Identifies A Functional Role For Calcium Signalling Pathway Member Camkii, Hong You, Donald P. Mcmanus, Wei Hu, Michael J. Smout, Paul J. Brindley, Geoffrey N. Gobert

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Treatment for clinical schistosomiasis has relied centrally on the broad spectrum anthelmintic praziquantel; however, there is limited information on its mode of action or the molecular response of the parasite. This paper presents a transcriptional and functional approach to defining the molecular responses of schistosomes to praziquantel. Differential gene expression in Schistosoma japonicum was investigated by transcriptome-wide microarray analysis of adult worms perfused from infected mice after 0.5 to 24 hours after oral administration of sub-lethal doses of praziquantel. Genes up-regulated initially in male parasites were associated with “Tegument/Muscle Repair” and “Lipid/Ion Regulation” functions and were followed by “Drug Resistance” …

Generation And Characterization Of Peptide Fusion Proteins, Brianna L. Probasco

Graduate School of Biomedical Sciences Theses and Dissertations

Pathogenic Th17 cells drive progression of many autoimmune diseases. Th17 cells develop from naïve T cells in the immune system after antigen-driven stimulation in a specific cytokine environment. Normally, T cells act to fight off infection, but when not properly controlled, they can cause disease. The cytokine interleukin-23 (IL-23) plays an essential role in the expansion of pathogenic Th17 cells. IL-23 is a heterodimeric protein, composed of a p19 alpha chain and a p40 beta chain. The p40 is also part of IL-12 and binds to the IL-12 receptor beta 1 (IL-12Rβ1) subunit. Thus, it follows that the IL-23 receptor …

Androgen Receptor-Target Genes In African American Prostate Cancer Disparities, Bi-Dar Wang, Qi Yang, Kristin Ceniccola, Fernando Bianco, Ramez Andrawis, Thomas W. Jarrett, Harold A. Frazier, Steven R. Patierno, Norman H. Lee

Pharmacology and Physiology Faculty Publications

The incidence and mortality rates of prostate cancer (PCa) are higher in African American (AA) compared to Caucasian American (CA) men. To elucidate the molecular mechanisms underlying PCa disparities, we employed an integrative approach combining gene expression profiling and pathway and promoter analyses to investigate differential transcriptomes and deregulated signaling pathways in AA versus CA cancers. A comparison of AA and CA PCa specimens identified 1,188 differentially expressed genes. Interestingly, these transcriptional differences were overrepresented in signaling pathways that converged on the androgen receptor (AR), suggesting that the AR may be a unifying oncogenic theme in AA PCa. Gene promoter …

Factors That Lead To The Immunotherapy Gap In Multiple Sclerosis Testing, Karthika Solai

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Multiple sclerosis is a disease that affects the central nervous system. Most doctors and scientists believe that it is an autoimmune disease. Simply put, the immune system attacks the nerves in a person’s body, thereby causing myelin damage, inflammation, and neurodegeneration. The plaque that then builds up on the nerves is scar tissue created when the wounds made by the immune system heal. It is this plaque that inhibits communication between the axons in the body and causes the symptoms of MS, which includes problems with movement, pain, vision problems, trouble swallowing, fatigue, and heat sensitivity (Baker et al., 2011, …

Investigating Therapeutic Options For Lafora Disease Using Structural Biology And Translational Methods, Amanda R. Sherwood

Theses and Dissertations--Molecular and Cellular Biochemistry

Lafora disease (LD) is a rare yet invariably fatal form of epilepsy characterized by progressive degeneration of the central nervous and motor systems and accumulation of insoluble glucans within cells. LD results from mutation of either the phosphatase laforin, an enzyme that dephosphorylates cellular glycogen, or the E3 ubiquitin ligase malin, the binding partner of laforin. Currently, there are no therapeutic options for LD, or reported methods by which the specific activity of glucan phosphatases such as laforin can be easily measured. To facilitate our translational studies, we developed an assay with which the glucan phosphatase activity of laforin as …

Merkel Cell Carcinoma, Cynthia L. Bartus Md, Steven Oberlender Md, Phd, Christian W. Oram Do

Department of Medicine

No abstract provided.

Aβ Alters The Dna Methylation Status Of Cell-Fate Genes In An Alzheimer’S Disease Model, Gary D. Isaacs, Noor Taher, Courtney Mckenzie, Rebecca Garrett, Matthew Baker, Nena Fox

Faculty Publications and Presentations

Alzheimer’s disease (AD) is characterized by neurofibrillary tangles and extracellular amyloid-β plaques (Aβ). Despite ongoing research, some ambiguity remains surrounding the role of Aβ in the pathogenesis of this neurodegenerative disease. While several studies have focused on the mutations associated with AD, our understanding of the epigenetic contributions to the disease remains less clear. To that end, we determined the changes in DNA methylation in differentiated human neurons with and without Aβ treatment. We isolated the DNA from neurons treated with Aβ or vehicle, and digested the two samples with either a methylation-sensitive (HpaII) or a methylation-insensitive (MspI) restriction endonuclease. …

Chlamydia Pneumoniae Infection Of Neuronal Cells Induces Changes In Calcium-Associated Gene Expression Consistent With Alzheimer’S Disease, Christopher Andrew Cappellini, Ahmad B. Cader, Keith G. Williams, Juliana Zoga, Susan T. Hingley

Scholarly Posters

Background and Significance: Previous studies have shown that cells infected with Chlamydia pneumoniae (Cpn) exhibit altered gene expression consistent with that observed in Alzheimer’s disease (AD). Furthermore, AD neurodegeneration has been linked to dysregulation of intracellular calcium and calcium-related processes. Therefore, we hypothesize that one mechanism by which pathogenesis evolves in AD is through infection-induced changes in expression of calcium-related genes. Objectives: To determine if infection of neuronal cells with Cpn alters expression of calciumrelated genes associated with neurodegeneration. Methods: SK-N-MC neuronal cells were infected with Cpn (AR39 strain; MOI=1) for 3 to 72 hours, then calcium-related genes were screened …

Analysis Of Autophagy And Inflammasome Regulation In Neuronal Cells And Monocytes Infected With Chlamydia Pneumoniae: Implications For Alzheimer’S Disease, Brian J. Balin, Christine J. Hammond, Juliana Zoga, Ahmad B. Cader, Annette K. Slutter, Jonathan M. Anzman, Ian Kohler, Susan T. Hingley, Denah M. Appelt

Scholarly Posters

Objectives: Our laboratory has been studying the role of infection with the obligate intracellular bacterium Chlamydia pneumoniae in sporadic late-onset Alzheimer disease (LOAD). This infection may be a trigger for the pathology observed in LOAD as a function of initiating changes in gene regulation following entry of the organism into the brain. As such, we are analyzing how this infection can promote changes in autophagy and inflammasome gene regulation as both have been shown to be altered in LOAD. Methods: Human SKNMC neuronal cells and THP1 monocytes were infected in vitro for 24-72 hrs with a laboratory strain of Chlamydia …

Is There An Alternative Way Of Treating Drug Resistant Epilepsy? The Effects Of The Ketogenic Diet In Children With Intractable Epilepsy, Chaya M. Weinberg

The Science Journal of the Lander College of Arts and Sciences

Many children with epilepsy experience seizures that cannot be resolved with medication. Since surgical intervention is not always an option, the ketogenic diet (KD). a high fat, low carbohydrate and protein diet, offers a chance for seizure reduction and in some cases freedom from seizures and medication. Side effects do exist, although none are serious. Efficacy has been proven through many studies. The mechanism of the KD's effectiveness is still unknown, although several hypotheses exist, including the theory that ketone bodies themselves are anticonvulsant, and the hypothesis that glucose restriction stops seizures. Adenosine A1 receptors are also thought to have …

Effects Of Intranasally Administered Dnsp-11 On The Central Dopamine System Of Normal And Parkinsonian Fischer 344 Rats, James H. Sonne

Theses and Dissertations--Neuroscience

Due to the blood-brain barrier, delivery of many drugs to the brain has required intracranial surgery which is prone to complication. Here we show that Dopamine Neuron Stimulating Peptide 11 (DNSP-11), following non-invasive intranasal administration, protects dopaminergic neurons from a lesion model of Parkinson’s disease in the rat. A significant and dose-dependent increase in an index of dopamine turnover (the ratio of DOPAC to dopamine) was observed in the striatum of normal young adult Fischer 344 rats by whole-tissue neurochemistry compared to vehicle administered controls.

Among animals challenged with a moderate, unilateral 6-hydroxy-dopamine (6-OHDA) lesion of the substantia nigra, those …

Mechanistic Basis For Atrial And Ventricular Arrhythmias Caused By Kcnq1 Mutations, Daniel C. Bartos

Theses and Dissertations--Physiology

Cardiac arrhythmias are caused by a disruption of the normal initiation or propagation of electrical impulses in the heart. Hundreds of mutations in genes encoding ion channels or ion channel regulatory proteins are linked to congenital arrhythmia syndromes that increase the risk for sudden cardiac death. This dissertation focuses on how mutations in a gene (KCNQ1) that encodes a voltage-gated K⁺ ion channel (Kv7.1) can disrupt proper channel function and lead to abnormal repolarization of atrial and ventricular cardiomyocytes.

In the heart, Kv7.1 coassembles with a regulatory protein to conduct the slowly activating delayed rectifier K^{+ …}