Medicine and Health Sciences Commons^™

Methods For Quantifying T Cell Receptor Binding Affinities And Thermodynamics, Kurt H. Piepenbrink, Brian E. Gloor, Kathryn M. Armstrong, Brian M. Baker

Food for Health: Publications

αβ T cell receptors (TCRs) recognize peptide antigens bound and presented by class I or class II major histocompatibility complex (MHC) proteins. Recognition of a peptide/MHC complex is required for initiation and propagation of a cellular immune response, as well as the development and maintenance of the T cell repertoire. Here we discuss methods to quantify the affinities and thermodynamics of interactions between soluble ectodomains of TCRs and their peptide/MHC ligands, focusing on titration calorimetry, surface plasmon resonance, and fluorescence anisotropy. As TCRs typically bind ligand with weak-to-moderate affinities, we focus the discussion on means to enhance the accuracy and …

Sustained Safety And Effectiveness Of Paclitaxel-Eluting Stents For Femoropopliteal Lesions: 2-Year Follow-Up From The Zilver Ptx Randomized And Single-Arm Clinical Studies., Michael D Dake, Gary M Ansel, Michael R Jaff, Takao Ohki, Richard R Saxon, H Bob Smouse, Scott A Snyder, Erin E O'Leary, Gunnar Tepe, Dierk Scheinert, Thomas Zeller, Zilver Ptx Investigators

Heart and Vascular Articles

Objectives: A prospective, multinational randomized controlled trial (RCT) and a complementary single-arm study evaluated the 2-year safety and effectiveness of a paclitaxel-coated drug-eluting stent (DES) in patients with superficial femoral artery lesions. The RCT compared the DES with percutaneous transluminal angioplasty (PTA) and provisional bare-metal stent (BMS) placement.

Background: Local drug delivery for superficial femoral artery lesions has been investigated with the intent of limiting restenosis similarly to DES for the coronary arteries. One-year outcomes of DES in the superficial femoral artery are promising, but longer-term benefits have not been established.

Methods: In the RCT, patients were randomly assigned to …

Post-Prandial Upright Exercise Echocardiography In Hypertrophic Cardiomyopathy, Ellina C. Feiner Md, Milla Arabadjian Fnp, Glenda Winson Rn, Bette Kim Md, Farooq Chaudhry Md, Mark V. Sherrid Md

Department of Medicine

No abstract provided.

A Preliminary Report Of Percutaneous Craniofacial Osteoplasty In A Rat Calvarium, William J. Parkes, Md, Jewel Greywoode, Md, Brian J. O'Hara, Md, Ryan N. Heffelfinger, Md, Howard Krein, Md, Phd

Department of Otolaryngology - Head and Neck Surgery Presentations and Grand Rounds

Objective: To evaluate the potential for injectable, permanent bone augmentation by assessing the biocompatibility and bioactivity of subperiosteal hydroxylapatite (Radiesse) deposition in a rat model.

Methods: Fourteen adult Sprague Dawley rats were injected in the parietal skull with hydroxylapatite (n=10) or a carrier gel control (n=4), using a subperiosteal injection technique on the right and a subcutaneous injection technique on the left. At 1, 3, and 6 months, 3 rats (1 negative control, 2 variables) were sacrificed. At 12 months, the remaining 5 rats were sacrificed. After each harvest, the calvaria were examined under both light and polarized microscopy.

Results: …

Protection Of Dietary Polyphenols Against Oral Cancer, Yijian Ding, Hua Yao, Yanan Yao, Leonard Yenwong Fai, Zhuo Zhang

Toxicology and Cancer Biology Faculty Publications

Oral cancer represents a health burden worldwide with approximate 275,000 new cases diagnosed annually. Its poor prognosis is due to local tumor invasion and frequent lymph node metastasis. Better understanding and development of novel treatments and chemo-preventive approaches for the preventive and therapeutic intervention of this type of cancer are necessary. Recent development of dietary polyphenols as cancer preventives and therapeutic agents is of great interest due to their antioxidant and anti-carcinogenic activities. Polyphenols may inhibit carcinogenesis in the stage of initiation, promotion, or progression. In particular, dietary polyphenols decrease incidence of carcinomas and exert protection against oral cancer by …

Dynamic And Opposing Adjustment Of Movement Cancellation And Generation In An Oculomotor Countermanding Task., Brian D Corneil, Joshua C Cheng, Samanthi C Goonetilleke

Brain and Mind Institute Researchers' Publications

Adaptive adjustments of strategies help optimize behavior in a dynamic and uncertain world. Previous studies in the countermanding (or stop-signal) paradigm have detailed how reaction times (RTs) change with trial sequence, demonstrating adaptive control of movement generation. Comparatively little is known about the adaptive control of movement cancellation in the countermanding task, mainly because movement cancellation implies the absence of an outcome and estimates of movement cancellation require hundreds of trials. Here, we exploit a within-trial proxy of movement cancellation based on recordings of neck muscle activity while human subjects attempted to cancel large eye-head gaze shifts. On a subset …

Dynamic Functions Of Rhoa In Tumor Cell Migration And Invasion, Kathleen L. O'Connor, Min Chen

Markey Cancer Center Faculty Publications

RhoA is one of the more extensively studied members of the Rho family of small GTPase where it is most readily recognized for its contributions to actin-myosin contractility and stress fiber formation. Accordingly, RhoA function during cell migration has been relegated to the rear of the cell where it mediates retraction of the trailing edge. However, RhoA can also mediate membrane ruffling, lamellae formation and membrane blebbing, thus suggesting an active role in membrane protrusions at the leading edge. With the advent of fluorescence resonance energy transfer (FRET)-based Rho activity reporters, RhoA has been shown to be active at the …

Restricted Likelihood Ratio Tests For Functional Effects In The Functional Linear Model, Bruce J. Swihart, Jeff Goldsmith, Ciprian M. Crainiceanu

Johns Hopkins University, Dept. of Biostatistics Working Papers

The goal of our article is to provide a transparent, robust, and computationally feasible statistical approach for testing in the context of scalar-on-function linear regression models. In particular, we are interested in testing for the necessity of functional effects against standard linear models. Our methods are motivated by and applied to a large longitudinal study involving diffusion tensor imaging of intracranial white matter tracts in a susceptible cohort. In the context of this study, we conduct hypothesis tests that are motivated by anatomical knowledge and which support recent findings regarding the relationship between cognitive impairment and white matter demyelination. R-code …

Intracranial Injection Of Gammagard, A Human Ivig, Modulates The Inflammatory Response Of The Brain And Lowers AΒ In App/Ps1 Mice Along A Different Time Course Than Anti-AΒ Antibodies, Tiffany L. Sudduth, Abigail Greenstein, Donna M. Wilcock

Sanders-Brown Center on Aging Faculty Publications

Gammagard IVIg is a therapeutic approach to treat Alzheimer's disease currently in phase 3 clinical trials. Despite the reported efficacy of the approach the mechanism of action is poorly understood. We have previously shown that intracranial injection of anti-Aβ antibodies into the frontal cortex and hippocampus reveals important information regarding the time course of events once the agent is in the brain. In the current study we compared IVIg, mouse-pooled IgG, and the anti-Aβ antibody 6E10 injected intracranially into the frontal cortex and hippocampus of 7-month-old APP/PS1 mice. We established a time course of events ranging from 1 …

Micu1 Controls Both The Threshold And Cooperative Activation Of The Mitochondrial Ca(2+) Uniporter., György Csordás, Tünde Golenár, Erin L Seifert, Kimberli J Kamer, Yasemin Sancak, Fabiana Perocchi, Cynthia Moffat, David Weaver, Sergio De La Fuente Perez, Roman Bogorad, Victor Koteliansky, Jeffrey Adijanto, Vamsi K Mootha, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Mitochondrial Ca(2+) uptake via the uniporter is central to cell metabolism, signaling, and survival. Recent studies identified MCU as the uniporter's likely pore and MICU1, an EF-hand protein, as its critical regulator. How this complex decodes dynamic cytoplasmic [Ca(2+)] ([Ca(2+)]c) signals, to tune out small [Ca(2+)]c increases yet permit pulse transmission, remains unknown. We report that loss of MICU1 in mouse liver and cultured cells causes mitochondrial Ca(2+) accumulation during small [Ca(2+)]c elevations but an attenuated response to agonist-induced [Ca(2+)]c pulses. The latter reflects loss of positive cooperativity, likely via the EF-hands. MICU1 faces the intermembrane space and responds to …

New Jersey Vaccine Mandates: The Confluence Of Regulations, Rights, And Religion, Drew Harris Dpm, Mph

Population Health Matters (Formerly Health Policy Newsletter)

No abstract provided.

Diabetes Mellitus And Hypercholesterolemia Are Risk Factors For Alzheimer’S Disease And Appear To Affect The Integrity Of The Blood Brain Barrier, Jacqueline Dash

Graduate School of Biomedical Sciences Theses and Dissertations

Studies have shown that the vascular risk factors common to diabetes mellitus and hypercholesterolemia are also risk factors for Alzheimer’s disease (AD). It is currently unknown how these diseases are associated with AD, but they may cause a leak in the blood brain barrier (BBB), which is one of the hallmarks of AD. In this preliminary study, over 150 pig brain slides were tested for the expression levels of tight junction proteins occludin and claudin V in the BBB microvasculature. There were three groups of pig brains used in this study namely, control pigs, pigs with diabetes mellitus and hypercholesterolemia …

A Th1 Immune Response Efficiently Clears Rabies Virus From The Cns In The Absence Of Inflammation, Aurore Lebrun, Rhonda Kean, Jianwei Li, Douglas Craig Hooper

Department of Cancer Biology Faculty Papers

Little is known about CD4+ T cell entry into the central nervous system (CNS) in the absence of inflammation. Attenuated rabies viruses (RABV) are unique tools to study this process, as they spread from the site of inoculation to the CNS trans-axonally, without compromising the blood-brain barrier. Previous studies with live-attenuated RABV showed that CD4+ T cell entry into the CNS is associated with an increase in IFN-g mRNA in the brain and the production of IgG2a antibodies in the periphery, indicating a bias towards TH1 immunity. To further investigate the nature of the CD4+ T cells involved in the …

Truncation Of Type Iv Pilin Induces Mucoidy In Pseudomonas Aeruginosa Strain Pao579, T. Ryan Withers, F. Heath Damron, Yeshi Yin, Hongwei D. Yu

Biochemistry and Microbiology

Pseudomonas aeruginosa is a Gram negative, opportunistic pathogen that uses the overproduction of alginate, a surface polysaccharide, to form biofilms in vivo. Overproduction of alginate, also known as mucoidy, affords the bacterium protection from the host's defenses and facilitates the establishment of chronic lung infections in individuals with cystic fibrosis. Expression of the alginate biosynthetic operon is primarily controlled by the alternative sigma factor AlgU (AlgT/σ²²). In a nonmucoid strain, AlgU is sequestered by the transmembrane antisigma factor MucA to the cytoplasmic membrane. AlgU can be released from MucA via regulated intramembrane proteolysis by proteases AlgW and MucP …

Two Distinct Ipsilateral Cortical Representations For Individuated Finger Movements., Jörn Diedrichsen, Tobias Wiestler, John W Krakauer

Brain and Mind Institute Researchers' Publications

Movements of the upper limb are controlled mostly through the contralateral hemisphere. Although overall activity changes in the ipsilateral motor cortex have been reported, their functional significance remains unclear. Using human functional imaging, we analyzed neural finger representations by studying differences in fine-grained activation patterns for single isometric finger presses. We demonstrate that cortical motor areas encode ipsilateral movements in 2 fundamentally different ways. During unimanual ipsilateral finger presses, primary sensory and motor cortices show, underneath global suppression, finger-specific activity patterns that are nearly identical to those elicited by contralateral mirror-symmetric action. This component vanishes when both motor cortices are …

Exploring Volatile General Anesthetic Binding To A Closed Membrane-Bound Bacterial Voltage-Gated Sodium Channel Via Computation., S G Raju, Annika F Barber, David N Lebard, Michael L Klein, Vincenzo Carnevale

Department of Neuroscience Faculty Papers

Despite the clinical ubiquity of anesthesia, the molecular basis of anesthetic action is poorly understood. Amongst the many molecular targets proposed to contribute to anesthetic effects, the voltage gated sodium channels (VGSCs) should also be considered relevant, as they have been shown to be sensitive to all general anesthetics tested thus far. However, binding sites for VGSCs have not been identified. Moreover, the mechanism of inhibition is still largely unknown. The recently reported atomic structures of several members of the bacterial VGSC family offer the opportunity to shed light on the mechanism of action of anesthetics on these important ion …

Expression Of The Chemokine Receptor, Cxcr4, And Its Ligand, Sdf-1, Are Increased In Purkinje Cells Of The Multiple System Atrophy Cerebellum, Megan Welter

Masters Theses

Multiple System Atrophy (MSA) is a sporadic, neurodegenerative disease that consists of three conditions: autonomic dysfunction, Parkinsonism and cerebellar ataxia. Our lab conducted an Affymetrix global gene expression analysis using pons tissue of MSA patients to determine genes that are differentially expressed when compared to non- MSA controls. This study identified upregulated genes, including the C-X-C chemokine receptor type 4, CXCR4, to which stromal cell-derived factor-I (SDF-1) is the natural ligand. The CXCR4/SDF-1 signaling pair has been sho.wn to play multiple roles in the brain, such as inducing neuronal apoptosis and promoting leukocyte recruitment during inflammation. The MSA cerebellum presents …

The 23rd Annual Research Conference Abstract Booklet, Mulu Aderie Alemu, Nikki Lynn Rogers

University of Gondar Research Conferences

Staff members, postgraduate and senior undergraduate students of the University, invited guests and speakers participated in the conference. The annual conference of the University is meant to share experiences in research activities among juniors and seniors, staff and students, and invited guests. It is also meant to motivate students and young faculty to engage in research and also to initiate and strengthen interdisciplinary collaborations. The findings of the studies and the resulting recommendations are expected to be used in solving the diverse societal problems we have been facing.

Research activities at the University of Gondar are primarily aimed at solving …

Uv Radiation And The Skin, John A. D'Orazio, Stuart G. Jarrett, Alexandra Amaro-Ortiz, Timothy Scott

Toxicology and Cancer Biology Faculty Publications

UV radiation (UV) is classified as a "complete carcinogen" because it is both a mutagen and a non-specific damaging agent and has properties of both a tumor initiator and a tumor promoter. In environmental abundance, UV is the most important modifiable risk factor for skin cancer and many other environmentally-influenced skin disorders. However, UV also benefits human health by mediating natural synthesis of vitamin D and endorphins in the skin, therefore UV has complex and mixed effects on human health. Nonetheless, excessive exposure to UV carries profound health risks, including atrophy, pigmentary changes, wrinkling and malignancy. UV is epidemiologically and …

Evaluation Of Clinical Outcomes Of Prophylactic Versus Preemptive Cytomegalovirus Strategy In Liver Transplant Recipients, Ifeanyi Onor, Sarah Todd, Erika Meredith, Sebastian Perez, Aneesh Mehta, G Lyon, Stuart Knechtle, Steven Hanish

Faculty and Staff Publications

Cytomegalovirus (CMV) is a major cause of morbidity and mortality following solid organ transplantation (SOT). Two strategies, prophylactic, and preemptive have emerged for the prevention of CMV infection and disease after SOT. This retrospective chart review of two liver transplant cohorts: prophylactic and preemptive, compares the clinical impact of transitioning from prophylactic to preemptive strategy. The primary outcome is the incidence of CMV viremia at 3-and 6-months post-transplant. Secondary outcomes include: incidence of CMV tissue-invasive disease, acute cellular rejection, leukopenia and neutropenia, opportunistic infection rates, hospital readmission rates, and mortality at 3-and 6-months post-transplant. A total of 109 patients were …

Vegf And Sympathetic Perivascular Nerves Contribute To Hypoxic Remodeling Of Ovine Cranial Arteries, Olayemi Olufikayo Adeoye

Loma Linda University Electronic Theses, Dissertations & Projects

Chronic hypoxia complicates many pregnancies and can result in postnatal pathologies that include compromised fetal cardiovascular structure and function. Mechanisms involved remain unclear. Because hypoxia increases production of VEGF, known to modulate smooth muscle (SM) phenotype, this thesis explored the hypothesis that VEGF contributes to hypoxic fetal vascular remodeling through direct effects on SM cells and indirectly through perivascular nerves. Using a chronic hypoxia sheep model, this work demonstrated that: 1) hypoxia potently upregulates VEGF receptor expression but not endogenous VEGF level in fetal ovine carotid arteries; 2) both chronic hypoxia and VEGF exert similar effects on smooth muscle contractile …

Effect Of Procedural Pain On Purines, Mda And Allantoin In Premature Infants, Megan Sue Holden

Loma Linda University Electronic Theses, Dissertations & Projects

Identifying and measuring the biochemical effects of procedural pain in infants is a continuing challenge for clinicians. To address this issue we evaluated the relationship between procedural pain, ATP utilization (hypoxanthine and uric acid), and oxidative stress (MDA and allantoin) in premature infants. Through these studies we found that 1) a single heel-lance significantly increases plasma uric acid in rabbit kits, 2) tape removal increases MDA and prevents a decrease in uric acid in the plasma of premature infants, and 3) a single dose of oral sucrose before a heel-lance is sufficient to significantly increase plasma markers of ATP utilization …

Small Molecule Inhibitors Of Hpv16 E6, Chung-Hsiang Yuan

Loma Linda University Electronic Theses, Dissertations & Projects

High-risk human papillomaviruses (HR-HPVs) cause nearly all cases of cervical cancer. HPV 16 E6, one of two viral oncogenes, protects cells from apoptosis by binding to and accelerating the degradation of several apoptotic proteins, including caspase 8 and p53. We proposed that blocking the interactions between HPV E6 and its partners using small molecules had the potential to re-sensitize HPV+ cells to apoptosis. To test this prediction, we screened libraries of small molecules for candidates that could block E6/caspase 8 binding, and identified several candidates from different chemical classes. Testing hits for dose-dependency and specificity in vitro and for toxicity …

Role Of Igf-Ii, Prl, And Fabps In The Breast Cancer Disparity Among Aa Women, Teleka Cassandra Patrick

Loma Linda University Electronic Theses, Dissertations & Projects

It is well documented that African-American (AA) patients present with more advanced states of breast cancer and have lower survival rates than Caucasian-Americans (CA). Epidemiological data have shown that pregnancy and lactation at an early age in humans reduce the risk of breast cancer. Studies in mice and rats have shown that lactation stimulates the expression of intracellular fatty-acid binding protein 3 (FABP3). FABP3 is detected in human breast tissue and is known as mammary-derived growth inhibitor (MDGI) because it has a strong inhibitory effect on cell proliferation. FABP5 is also expressed in the breast, and has been associated with …

Microglia And Complement In Alzheimer's Disease With Cerebral Amyloid Angiopathy, Matthew K. Zabel

Loma Linda University Electronic Theses, Dissertations & Projects

Alzheimer’s disease (AD) is the most common form of dementia and completely lacks any viable, long-term therapeutic intervention. This is partly due to an incomplete understanding of AD etiology and the possible confounding factors associated with its genotypic and phenotypic heterogeneity. Cerebral amyloid angiopathy (CAA) is a common, yet frequently overlooked, pathology associated with AD. A pathological hallmark of AD consists of extracellular amyloid-beta (Aβ) deposits, while CAA

manifests with deposition Aβ within the smooth muscle layer of cerebral arteries and arterioles. The role of Aβ in AD and CAA pathophysiology has long been controversial. Although it may have toxic …

Perinatal Nicotine Exposure And Programming Of Hie Sensitive Phenotype In Neonatal Rat Brains, Yong Li

Loma Linda University Electronic Theses, Dissertations & Projects

Large epidemiological and animal studies have revealed a clear association of adverse intrauterine environment with the increased risk of metabolic, cardiovascular and neurological diseases. Maternal smoking is the single most widespread perinatal insult in the world and has been associated with adverse pregnancy outcomes for mother, fetus and the newborn. Our study aims to test the hypothesis that perinatal nicotine exposure induces reprogramming of susceptibility to hypoxic ischemic brain injury in the immature brain, focusing on the roles of AT1R and/or AT2R and trying to reveal the underlying epigenetic mechanisms. Therefore, we established two rat models: perinatal nicotine exposure model …

Associations Between Alcohol Consumption And Fasting Blood Glucose In Young Adults, Julie Ann Lucca

Master's Theses

Current research shows moderate alcohol consumption is associated with decreased risk of diabetes and excessive consumption or binge drinking can cause insulin resistance and diabetes. In 2010, diabetes was the seventh leading cause of death in the United Statesand was responsible for significant health complications: blindness, kidney failure, and limb amputations, and is a large national economic burden. Fasting blood glucose (FBG) is a tool used to help diagnose diabetes. Abnormally high FBG, ≥100 mg/dl, is indicative of diabetes and pre-diabetes. Few studies have observed diabetic prevalence among young adults or college students. Studying young adults can help provide added …

Crash Course In United States Pharmacopeia Standard 797 (Usp 797): Investigation Of Positive Sterility Cultures From A Hospital Pharmacy Preparation, Terry Burger Mba, Bsn, Rn, Ne-Bc, Cic, Deborah Fry Mt (Ascp), Mba, Cic, Gary Tallarita Mt (Ascp), Cindy L. Mitman Pharm D

Department of Medicine

No abstract provided.

Closing The Gap: Revising Sterility Testing Policies And Procedures Based On The United States Pharmacopeia (Usp) 797 Guidelines And A Near Miss, Cindy L. Mitman Pharm D, Terry Burger Mba, Bsn, Rn, Ne-Bc, Cic, Deborah Fry Mt (Ascp), Mba, Cic, Gary Tallarita Mt (Ascp)

Department of Medicine

No abstract provided.

Durability, Reliability, Viability: 48 Year-Survival Of A Starr-Edwards Mitral Valve, Bilal Ayub, Justin L. Guthier, James K. Wu

Department of Medicine

No abstract provided.