Medical Sciences Commons^™

Imaging Of Lung Function Using Hyperpolarized Helium-3 Magnetic Resonance Imaging: Review Of Current And Emerging Translational Methods And Applications, Sean Fain, Mark L Schiebler, David G Mccormack, Grace Parraga

Medical Biophysics Publications

During the past several years there has been extensive development and application of hyperpolarized helium-3 (HP (3)He) magnetic resonance imaging (MRI) in clinical respiratory indications such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, radiation-induced lung injury, and transplantation. This review focuses on the state-of-the-art of HP (3)He MRI and its application to clinical pulmonary research. This is not an overview of the physics of the method, as this topic has been covered previously. We focus here on the potential of this imaging method and its challenges in demonstrating new types of information that has the potential to influence clinical …

Influence Of Sex On Long-Term Outcomes After Percutaneous Coronary Intervention With The Paclitaxel-Eluting Coronary Stent: Results Of The "Taxus Woman" Analysis, Ghada W. Mikhail Md, Robert T. Gerber Md, Phd, David A. Cox Md, Stephen G. Ellis Md, John M. Lasala Md, Phd, John A. Ormiston Mbchb, Gregg W. Stone Md, Mark A. Turco Md, Anita A. Joshi Phd, Donald S. Baim Md, Antonio Colombo Md

Department of Medicine

No abstract provided.

D2r Dopamine Receptor Mediates Changes In Dual Specificity Phosphatase Expression In A Small Cell Lung Cancer Cell Line, Scott Lemar Lattimer

Theses and Dissertations (ETD)

Bromocriptine, a D2 dopamine receptor (D2R) agonist, is used clinically as a treatment for pituitary tumors of a lactotroph origin. Many questions remain unanswered about the mechanism of this effect. The antiproliferative effect has not been demonstrated in DMS 53 cell line, a Small Cell Lung Cancer (SCLC). In this thesis, we have shown that treatment with NPA (N‑propylnorapomorphine), a dopamine receptor agonist inhibits ERK phosphorylation and proliferation in DMS 53 cells. NPA treatment causes significant increases in DUSP‑1 (MKP‑1), DUSP‑4 (MKP‑2) and DUSP5 mRNA. NPA treatment also correlates with increases in DUSP5 (hVHR3) protein visualized using Western Blot. These …

Fat Taste Transduction In Mouse Taste Cells: The Role Of Transient Receptor Potential Channel Type M5, Pin Liu

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

A number of studies have demonstrated the ability of free fatty acids to activate taste cells and elicit behavioral responses consistent with there being a taste of fat. Here I show for the first time that long chain unsaturated free fatty acid, linoleic acid, depolarizes taste cells and elicits a robust intracellular calcium rise via the activation of transient receptor potential channel type M5. The linoleic acid-induced responses depend on G protein-phospholipase C pathway indicative of the involvement of G protein-coupled receptors in the transduction of fatty acids. Mice lacking transient receptor potential channel type M5 exhibit no preference for …

Cerebral Amyloid Angiopathy And Transition Metals In Alzheimer's Disease, Matthew Schrag

Loma Linda University Electronic Theses, Dissertations & Projects

Alterations in brain metals homeostasis and particularly brain iron overload have been postulated to play a role in Alzheimer's disease, contributing to oxidative stress and neuronal injury; however, the source of this iron is not clear and may be due to metabolic derangement(s), failed iron clearance mechanisms or exogenous deposition such as through bleeding. This series of studies was designed to evaluate the extent of metals dyshomeostasis in the Alzheimer's disease brain and specifically whether microvascular bleeding is a major contributor to Alzheimer's disease-related iron overload. Cerebral amyloid angiopathy (CAA) is a vascular manifestation of Alzheimer's disease present to some …

Cd151 Reinforces Vascular Stability By Balancing Endothelial Cell Adhesion And Cytoskeletal Tension, Feng Zhang

Theses and Dissertations (ETD)

Tetraspanin CD151 is highly expressed in endothelial cells and regulates pathological angiogenesis. However, the mechanism by which CD151 promotes vascular morphogenesis and whether CD151 engages other vascular functions are unclear. We observed that CD151 is required for the maintenance of endothelial capillary-like structures formed in vitro and the integrity of lung endothelial cell-cell contacts in vivo. As a master regulator of endothelial cell-matrix and cell-cell adhesions, CD151 is needed for the optimal functions of various cell adhesion proteins such as integrin, cadherin, and CD44. The loss of CD151 elevates the cellular intrinsic contraction by upregulating RhoA signaling and downregulating of …

Study Of The Structure And Function Of Cxc Chemokine Receptor 2, Hae Ryong Kwon

Masters Theses

It has been shown that the amino terminus and second extracellular loop (EC2) of CXCR2 are crucial for ligand binding and receptor activation. The lack of an ionic lock motif in the third intracellular loop of CXCR2 focuses an investigation of the mechanism by which these two extracellular regions contribute to receptor recognition and activation.

The first objective of this investigation was to predict the structure of CXCR2 based on known structures of crystallized GPCRs. Rhodopsin, β2-adrenergic receptor, CXCR4 were used for homology modeling of CXCR2 structure. Highly conserved motifs found in sequence alignments of the template GPCRs were helpful …

Donepezil And Galanin Interactions In An Animal Model Of Alzheimer’S Disease, Jonathan J. Sabbagh

UNLV Theses, Dissertations, Professional Papers, and Capstones

Alzheimer's disease (AD) is a neurodegenerative disorder marked by a progressive loss of cognitive function. One of the neurobiological hallmarks of AD is a progressive loss of cholinergic neurons and a decrease in the amount of acetylcholine in the brain. Pharmacological therapies have targeted the cholinergic system, specifically first-line, palliative treatment using acetylcholinesterase (AChE) inhibitors, such as donepezil. Donepezil has been shown to increase cholinergic tone and ameliorate some of the cognitive deficits in AD patients. Galanin, a neuropeptide that inhibits the evoked release of several neurotransmitters including acetylcholine as well as modulates seveal intracellular cascades, is overexpressed in AD …

Protocol Variation Analysis Of Whole Brain Ct Perfusion In Acute Ischemic Stroke, Peter T. Heiberger

UNLV Theses, Dissertations, Professional Papers, and Capstones

Computed tomography perfusion (CTP) analysis is a rapidly advancing imaging modality that is improving diagnosis of brain abnormalities in patients suffering from hemorrhagic or ischemic stroke, traumatic brain injury, vascular occlusion and numerous other conditions. Through the advancements of computed tomography (CT) imaging, including the introduction of the 320-detector row CT with a 16 centimeter range in the z-axis enabling whole brain CTP, perfusion analysis now has a significantly increased clinical utility that is useful for both diagnosis and treatment of central nervous system (CNS) conditions. This study focuses on the procedural and analytical approach to the diagnostic evaluation of …

Acetate Causes Alcohol Hangover Headache In Rats., Christina R Maxwell, Rebecca Jay Spangenberg, Jan B Hoek, Stephen D Silberstein, Michael L Oshinsky

Department of Neurology Faculty Papers

BACKGROUND: The mechanism of veisalgia cephalgia or hangover headache is unknown. Despite a lack of mechanistic studies, there are a number of theories positing congeners, dehydration, or the ethanol metabolite acetaldehyde as causes of hangover headache.

METHODS: We used a chronic headache model to examine how pure ethanol produces increased sensitivity for nociceptive behaviors in normally hydrated rats.

RESULTS: Ethanol initially decreased sensitivity to mechanical stimuli on the face (analgesia), followed 4 to 6 hours later by inflammatory pain. Inhibiting alcohol dehydrogenase extended the analgesia whereas inhibiting aldehyde dehydrogenase decreased analgesia. Neither treatment had nociceptive effects. Direct administration of acetate …

Long-Term Hypoxia Regulates Cortisol Biosynthesis In The Ovine Fetal Adrenal Cortex, Vladimir Enrique Vargas

Loma Linda University Electronic Theses, Dissertations & Projects

Previous studies demonstrated enhanced fetal adrenal cortisol biosynthesis following exposure to long-term hypoxia (LTH). The studies presented here were designed to determine the mechanism(s) regulating this important adaptive endocrine response. Ewes were maintained at high altitude (3,820 m) from approximately day 40 to 138-141 of gestation. Fetal adrenal glands were then collected from LTH and age matched normoxic controls. Dispersed fetal adrenal cortical cells (FACs) were untreated, treated with ACTH, treated in combination with ACTH precursors (POMC and 22-kDa pro-ACTH), or pre-treated with H-89 and or UO126 followed by ACTH treatment. Following ACTH treatment, cortisol biosynthesis increased in both groups …

Mechanism Of N-Methylation By The Trna M1g37 Methyltransferase Trm5., Thomas Christian, Georges Lahoud, Cuiping Liu, Katherine Hoffmann, John J Perona, Ya-Ming Hou

Department of Biochemistry and Molecular Biology Faculty Papers

Trm5 is a eukaryal and archaeal tRNA methyltransferase that catalyzes methyl transfer from S-adenosylmethionine (AdoMet) to the N(1) position of G37 directly 3' to the anticodon. While the biological role of m(1)G37 in enhancing translational fidelity is well established, the catalytic mechanism of Trm5 has remained obscure. To address the mechanism of Trm5 and more broadly the mechanism of N-methylation to nucleobases, we examined the pH-activity profile of an archaeal Trm5 enzyme, and performed structure-guided mutational analysis. The data reveal a marked dependence of enzyme-catalyzed methyl transfer on hydrogen ion equilibria: the single-turnover rate constant for methylation increases by one …

Hydroxyurea And Acute Painful Crises In Sickle Cell Anemia: Effects On Hospital Length Of Stay And Opioid Utilization During Hospitalization, Outpatient Acute Care Contacts, And At Home, Samir K. Ballas, Md, Facp, Robert L. Bauserman, Phd, William F. Mccarthy, Phd, Oswaldo L. Castro, Md, Wally R. Smith, Md, Myron A. Waclawiw, Phd

Department of Medicine Faculty Papers

Recurrent acute sickle cell painful crises are the hallmark of sickle cell anemia. These events may be mild, moderate or severe in nature and often require treatment at home, in acute care facilities as outpatients, and in the hospital with oral and/or parenteral opioids. The type, dose, route & frequency of administration of opioids, as well as the length of hospital stay (LOS), are not well known for adults with sickle cell anemia (SS). We analyzed these aspects in the 299 patients enrolled in the Multicenter Study of Hydroxyurea (MSH) in SS. For these patients there were 16818 home diaries, …

The Face Of Felt Stigma: Experiences Of Puerto Ricans Living With Hiv In Allentown, Pa, M Reyes Ba, Julio Jiménez Md, Joseph L. Yozviak Do, Facp, Timothy J. Friel Md, D Adams Psyd, Cynthia Beitler, Eric J. Gertner Md, Mph, E Rivera Ba, L Santiago Phd

Department of Medicine

No abstract provided.

Elucidating The Role Of Cd44 Expression On Mesenchymal Stem Cells Within The Tumor Microenvironment, Erika L. Spaeth

Dissertations & Theses (Open Access)

The tumor microenvironment is comprised of a vast array of heterogeneous cells including both normal and neoplastic cells. The tumor stroma recruitment process has been exploited for an effective gene delivery technique using bone marrow derived MSC. Targeted migration of the MSC toward the tumor microenvironment, while successful, is not yet fully understood. This study was designed to assess the role of CD44 in the migration of MSC toward the tumor microenvironment and to determine the implications of CD44-deficient MSC within the tumor stroma. Inhibition of MSC migration was evaluated through a variety of methods in vitro and in vivo …

Bimanual Reaching Across The Hemispace: Which Hand Is Yoked To Which?, Gavin Buckingham, Gordon Binsted, David Carey

Gavin Buckingham

When both hands perform concurrent goal-directed reaches, they become yoked to one another. To investigate the direction of this coupling (i.e., which hand is yoked to which), the temporal dynamics of bimanual reaches were compared with equivalent-amplitude unimanual reaches. These reaches were to target pairs located on either the left or right sides of space; meaning that in the bimanual condition, one hand's contralateral (more difficult) reach accompanied by the other hand's ipsilateral (easier) reach. By comparing which hand's difficult reach was improved more by the presence of the other hand's easier ipsilateral reach, we were able to demonstrate asymmetries …

Biological Rationale For The Use Of Dna Methyltransferase Inhibitors As New Strategy For Modulation Of Tumor Response To Chemotherapy And Radiation., Giovanni L Gravina, Claudio Festuccia, Francesco Marampon, Vladimir M Popov, Richard G Pestell, Bianca M Zani, Vincenzo Tombolini

Kimmel Cancer Center Faculty Papers

Epigenetic modifications play a key role in the patho-physiology of many tumors and the current use of agents targeting epigenetic changes has become a topic of intense interest in cancer research. DNA methyltransferase (DNMT) inhibitors represent a promising class of epigenetic modulators. Research performed yielded promising anti-tumorigenic activity for these agents in vitro and in vivo against a variety of hematologic and solid tumors. These epigenetic modulators cause cell cycle and growth arrest, differentiation and apoptosis. Rationale for combining these agents with cytotoxic therapy or radiation is straightforward since the use of DNMT inhibitor offers greatly improved access for cytotoxic …

Attitudes Of Health Professionals To Electronic Data Sharing Within An Integrated Care Electronic Health Record (Icehr), Charyl O'Malley, Damon Berry, Mary Sharp

Conference Papers

It is estimated that 98,000 people die in hospitals yearly in the USA as a result of medical errors (Agency for Healthcare Research and Quality, 2009). Electronic Health Records (EHR) can offer improved patient safety. EHRs are being implemented by many countries, however, not all health professionals have welcomed them (MORI Social Research Institute, 2006). As outlined in the National Health Information Strategy (NHIS) document, Ireland has plans to introduce an EHR. Attitudes of health professionals are a significant factor for the successful implementation and adoption of a new clinical information system. This study aimed to gauge the attitude of …

Self-Protecting Bactericidal Titanium Alloy Surface Formed By Covalent Bonding Of Daptomycin Bisphosphonates., Chang-Po Chen, Eric Wickstrom

Department of Biochemistry and Molecular Biology Faculty Papers

Infections are a devastating complication of titanium alloy orthopedic implants. Current therapy includes antibiotic-impregnated bone cement and antibiotic-containing coatings. We hypothesized that daptomycin, a Gram-positive peptide antibiotic, could prevent bacterial colonization on titanium alloy surfaces if covalently bonded via a flexible, hydrophilic spacer. We designed and synthesized a series of daptomycin conjugates for bonding to the surface of 1.0 cm² Ti6Al4V foils through bisphosphonate groups, reaching a maximum yield of 180 pmol/cm². Daptomycin-bonded foils killed 53 ± 5% of a high challenge dose of 3 × 10⁵ cfu Staphylococcus aureus ATCC 29213.

Carhsp1 Is Required For Effective Tumor Necrosis Factor Alpha Mrna Stabilization And Localizes To Processing Bodies And Exosomes, Jason R. Pfeiffer, Bethany L. Mcavoy, Ryan E. Fecteau, Kristen M. Deleault, Seth A. Brooks

Dartmouth Scholarship

Tumor necrosis factor alpha (TNF-α) is a critical mediator of inflammation, and its production is tightly regulated, with control points operating at nearly every step of its biosynthesis. We sought to identify uncharacterized TNF-α 3' untranslated region (3'UTR)-interacting proteins utilizing a novel screen, termed the RNA capture assay. We identified CARHSP1, a cold-shock domain-containing protein. Knockdown of CARHSP1 inhibits TNF-α protein production in lipopolysaccharide (LPS)-stimulated cells and reduces the level of TNF-α mRNA in both resting and LPS-stimulated cells. mRNA stability assays demonstrate that CARHSP1 knockdown decreases TNF-α mRNA stability from a half-life (t(1/2)) of 49 min to a t(1/2) …

T-Lymphocyte Responses To Intestinally Absorbed Antigens Can Contribute To Adipose Tissue Inflammation And Glucose Intolerance During High Fat Feeding, Yuehui Wang, Jianing Li, Lihua Tang, Yu Wang, Richard Charnigo, Willem De Villiers, Erik Eckhardt

Internal Medicine Faculty Publications

BACKGROUND: Obesity is associated with inflammation of visceral adipose tissues, which increases the risk for insulin resistance. Animal models suggest that T-lymphocyte infiltration is an important early step, although it is unclear why these cells are attracted. We have recently demonstrated that dietary triglycerides, major components of high fat diets, promote intestinal absorption of a protein antigen (ovalbumin, "OVA"). The antigen was partly transported on chylomicrons, which are prominently cleared in adipose tissues. We hypothesized that intestinally absorbed gut antigens may cause T-lymphocyte associated inflammation in adipose tissue.

METHODOLOGY/PRINCIPAL FINDINGS: Triglyceride absorption promoted intestinal absorption of OVA into adipose tissue, …

Concurrent Validation Of The Dash And The Quickdash In Comparison To Neck-Specific Scales In Patients With Neck Pain, Saurabh Mehta, Joy Macdermid, Lisa Carlesso, Colleen Mcphee

Physical Therapy Faculty Research

Study Design. Concurrent validity study.

Objective. To examine the validity of the Disabilities of Arm, Shoulder, and Hand (DASH) and the QuickDASH in patients with neck pain in comparison with the Neck Disability Index (NDI), the Cervical Spine Outcome Questionnaire (CSOQ), and the Visual Analogue Scale (VAS) for pain. To examine the agreement between the DASH and the QuickDASH and assess whether the QuickDASH can be used instead of full DASH in patients with neck pain.

Summary of Background Data. NDI is commonly used for measuring neck-related disability in patients with neck pain; but it does not offer to assess …

Nanosized Hydroxyapatite And Other Calcium Phosphates: Chemistry Of Formation And Application As Drug And Gene Delivery Agents, Vuk Uskoković, Dragan Uskoković

Pharmacy Faculty Articles and Research

The first part of this review looks at the fundamental properties of hydroxyapatite (HAP), the basic mineral constituent of mammalian hard tissues, including the physicochemical features that govern its formation by precipitation. A special emphasis is placed on the analysis of qualities of different methods of synthesis and of the phase transformations intrinsic to the formation of HAP following precipitation from aqueous solutions. This serves as an introduction to the second part and the main subject of this review, which relates to the discourse regarding the prospects of fabrication of ultrafine, nanosized particles based on calcium phosphate carriers with various …

Sub-Wavelength Plasmonic Readout For Direct Linear Analysis Of Optically Tagged Dna, Jonathan Varsanik, William Teynor, John Leblanc, Heather Clark, Jeffrey Krogmeier, Tian Yang, Jonathan Bernstein

Heather Clark

This work describes the development and fabrication of a novel nanofluidic flow-through sensing chip that utilizes a plasmonic resonator to excite fluorescent tags with sub-wavelength resolution. We cover the design of the microfluidic chip and simulation of the plasmonic resonator using Finite Difference Time Domain (FDTD) software. The fabrication methods are presented, with testing procedures and preliminary results. This research is aimed at improving the resolution limits of the Direct Linear Analysis (DLA) technique developed by US Genomics. In DLA, intercalating dyes which tag a specific 8 base-pair sequence are inserted in a DNA sample. This sample is pumped though …

Failing To Ignore: Paradoxical Neural Effects Of Perceptual Load On Early Attentional Selection In Normal Aging, Taylor W. Schmitz, Frederick H.T. Cheng, Eve De Rosa

Brain and Mind Institute Researchers' Publications

We examined visual selective attention under perceptual load - simultaneous presentation of task-relevant and -irrelevant information - in healthy young and older adult human participants to determine whether age differences are observable at early stages of selection in the visual cortices. Participants viewed 50/50 superimposed face/place images and judged whether the faces were male or female, rendering places perceptible but task-irrelevant. Each stimulus was repeated, allowing us to index dynamic stimulus-driven competition from places. Consistent with intact early selection in young adults, we observed no adaptation to unattended places in parahippocampal place area (PPA) and significant adaptation to attended faces …

A Novel Totivirus And Piscine Reovirus (Prv) In Atlantic Salmon (Salmo Salar) With Cardiomyopathy Syndrome (Cms), Torstein Tengs

Dr. Torstein Tengs

BACKGROUNDCardiomyopathy syndrome (CMS) is a severe disease affecting large farmed Atlantic salmon. Mortality often appears without prior clinical signs, typically shortly prior to slaughter. We recently reported the finding and the complete genomic sequence of a novel piscine reovirus (PRV), which is associated with another cardiac disease in Atlantic salmon; heart and skeletal muscle inflammation (HSMI). In the present work we have studied whether PRV or other infectious agents may be involved in the etiology of CMS.RESULTSUsing high throughput sequencing on heart samples from natural outbreaks of CMS and from fish experimentally challenged with material from fish diagnosed with CMS …

Effect Of Low-Dose Aspirin Or Calcium Supplementation On The Incidence Of Pre-Eclampsia Among Pregnant Women, Philadelphia University

Philadelphia University, Jordan

No abstract provided.

Characterization And Development Of A Stroke-Induced Model Of Acquired Epilepsy In Organotypic Hippocampal Slice Cultures: Role Of The Cannabinoid Cb1 Receptors In Modulation Of Neuronal Excitation And Inhibition, Julie Ziobro

Theses and Dissertations

Stroke is the most common cause of acquired epilepsy in persons 35 and older. The massive increase in extracellular glutamate during stroke causes a cascade of intracellular events that can lead to cell death or the molecular changes that initiate the development of epilepsy. In addition, many studies point to a modulatory role of the endocannabinoid system in controlling seizures. Animal models of stroke induced acquired epilepsy have been difficult to develop. Therefore, this dissertation was initiated to develop an organotypic hippocampal slice culture model of acquired epilepsy and examine the changes in distribution and function of the endogenous CB1 …

Pp32 (Anp32a) Expression Inhibits Pancreatic Cancer Cell Growth And Induces Gemcitabine Resistance By Disrupting Hur Binding To Mrnas., Timothy K Williams, Christina L Costantino, Nikolai A Bildzukewicz, Nathan G Richards, David W Rittenhouse, Lisa Einstein, Joseph A Cozzitorto, Judith C Keen, Abhijit Dasgupta, Myriam Gorospe, Gregory E Gonye, Charles J Yeo, Agnieszka K Witkiewicz, Jonathan R Brody

Department of Surgery Faculty Papers

The expression of protein phosphatase 32 (PP32, ANP32A) is low in poorly differentiated pancreatic cancers and is linked to the levels of HuR (ELAV1), a predictive marker for gemcitabine response. In pancreatic cancer cells, exogenous overexpression of pp32 inhibited cell growth, supporting its long-recognized role as a tumor suppressor in pancreatic cancer. In chemotherapeutic sensitivity screening assays, cells overexpressing pp32 were selectively resistant to the nucleoside analogs gemcitabine and cytarabine (ARA-C), but were sensitized to 5-fluorouracil; conversely, silencing pp32 in pancreatic cancer cells enhanced gemcitabine sensitivity. The cytoplasmic levels of pp32 increased after cancer cells are treated with certain stressors, …

Solar Radiation Damage To Human Skin Mitochondria, Luciene Zanchetta

Doctoral

The central objective of this study was to assess solar radiation-induced changes in cellular function, mitochondrial function and mitochondrial DNA to further investigate the role of these energy-dedicated and metabolically essential organelles in the response to the main environmental stressor associated with skin cancer initiation. An in vitro approach was chosen employing the human malignant melanoma (A375) and human amelanotic melanoma (C32) cells and the human spontaneously immortalized keratinocytes (HaCaT). A Q-Sun Solar Simulator was used to expose cells to low-level simulated solar radiation (SSR) as it provides a mimic of solar radiation that is environmentally relevant in the UV …