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Qcm Aptasensor For Rapid And Specific Detection Of Avian Influenza Virus, Luke Brockman

Graduate Theses and Dissertations

There has been a need for rapid detection of avian influenza virus (AIV) H5N1 due to it being a potential pandemic threat. Most of the current methods, including culture isolation and PCR, are very sensitive and specific but require specialized laboratories and trained personnel in order to complete the tests and are time-consuming. The goal of this study was to design a biosensor that would be able to rapidly detect AIV H5N1 using aptamers as biosensing material and a quartz crystal microbalance (QCM) for transducing method. Specific DNA aptamers against AIV H5N1 were immobilized, through biotin and streptavidin conjugation, onto …

Alpcs(2a)-Mediated Photochemical Internalization Of Bleomycin And Concurrent Hyperthermia Of Multicellular Tumor Spheroids, Aaron Andersen

UNLV Theses, Dissertations, Professional Papers, and Capstones

Treatments for glioblastoma multiforme and invasive ductal carcinoma involve surgical resection and adjuvant or concurrent targeted therapies. The goal of the secondary treatment is to reduce the cancer cells in the resection margin and other areas of suspected involvement. Photochemical internalization is a targeted therapy using light to activate photosensitizers embedded in cellular structures to improve the delivery of macromolecules within the cell.

In a previous study, optimized treatment parameters including radiant exposure, and irradiance, concentration of AlPcS(2a), temperature, and the concentration of bleomycin were determined for human ACBT glioma multicell spheroids. The current study investigates the effectiveness of the …

A Public Health Response Against Strongyloides Stercoralis: Time To Look At Soil-Transmitted Helminthiasis In Full., Alejandro J Krolewiecki, Patrick Lammie, Julie Jacobson, Albis-Francesco Gabrielli, Bruno Levecke, Eugenia Socias, Luis M Arias, Nicanor Sosa, David Abraham, Ruben Cimino, Adriana Echazú, Favio Crudo, Jozef Vercruysse, Marco Albonico

Department of Microbiology and Immunology Faculty Papers

Strongyloides stercoralis infections have a worldwide distribution with a global burden in terms of prevalence and morbidity that is largely ignored. A public health response against soil-transmitted helminth (STH) infections should broaden the strategy to include S. stercoralis and overcome the epidemiological, diagnostic, and therapeutic challenges that this parasite poses in comparison to Ascaris lumbricoides, Trichuris trichiura, and hookworms. The relatively poor sensitivity of single stool evaluations, which is further lowered when quantitative techniques aimed at detecting eggs are used, also complicates morbidity evaluations and adequate drug efficacy measurements, since S. stercoralis is eliminated in stools in a larval stage. …

Novel Therapeutic Targets Identified By High-Throughput Technologies For Triple-Negative Breast Cancer, Christine Shiang

Dissertations and Theses (Open Access)

Triple-negative breast cancers (TNBC) are characterized by the lack of or reduced expression of the estrogen and progesterone receptors, and normal expression of the human epidermal growth factor receptor 2. The lack of a well-characterized target for treatment leaves only systemic chemotherapy as the mainstay of treatment. Approximately 60-70% of patients are chemosensitive, while the remaining majority does not respond. Targeted therapies that take advantage of the unique molecular perturbations found in triple-negative breast cancer are needed. The genes that are frequently amplified or overexpressed represent potential therapeutic targets for triple-negative breast cancer. The purpose of this study was to …

Design, Synthesis And Development Of Transporter Targeting Agents For Image-Guided Therapy And Drug Delivery, Ning Tsao

Dissertations and Theses (Open Access)

The purpose of this study was to design, synthesize and develop novel transporter targeting agents for image-guided therapy and drug delivery. Two novel agents, N4-guanine (N4amG) and glycopeptide (GP) were synthesized for tumor cell proliferation assessment and cancer theranostic platform, respectively. N4amG and GP were synthesized and radiolabeled with ^99mTc and ⁶⁸Ga. The chemical and radiochemical purities as well as radiochemical stabilities of radiolabeled N4amG and GP were tested. In vitro stability assessment showed both ^99mTc-N4amG and ^99mTc-GP were stable up to 6 hours, whereas ⁶⁸Ga-GP was stable up to 2 hours. Cell culture studies …

Completely Steroid-Free Immunosuppression In Liver Transplantation: A Randomized Study., Carlo B. Ramirez, Md, Cataldo Doria, Md, Phd, Adam M. Frank, Md, Stephen T. Armenti, Ignazio R. Marino, Md

Department of Surgery Faculty Papers

INTRODUCTION: Corticosteroids (CS) have been standard immunosuppression to prevent and treat rejection. However, CS are associated with increased risk of infection, obesity, hypertension, hyperlipidemia, diabetes, and accelerated hepatitis C virus (HCV) recurrence post-orthotopic liver transplantation (OLT). This study assesses the safety and efficacy of CS-free immunosuppressive regimen in adult OLT.

METHODS: A two-yr, prospective, randomized study of CS with delayed withdrawal (CS) or CS-free regimen with basiliximab, tacrolimus, and enteric-coated mycophenolate sodium (EC-MPS) was performed in 39 patients (CS=20; CS-free=19). CS group received intra-operative methylprednisolone weaned by six months. HCV patients had HCV PCR pre-OLT and 0.5, one, three, and …

Cavin1; A Regulator Of Lung Function And Macrophage Phenotype., Praveen Govender, Freddy Romero, Dilip Shah, Jesus Paez, Shi-Ying Ding, Libin Liu, Adam Gower, Elizabeth Baez, Sherif Shawky Aly, Paul Pilch, Ross Summer

Center for Translational Medicine Faculty Papers

Caveolae are cell membrane invaginations that are highly abundant in adipose tissue, endothelial cells and the lung. The formation of caveolae is dependent on the expression of various structural proteins that serve as scaffolding for these membrane invaginations. Cavin1 is a newly identified structural protein whose deficiency in mice leads to loss of caveolae formation and to development of a lipodystrophic phenotype. In this study, we sought to investigate the functional role of Cavin1 in the lung. Cavin1 deficient mice possessed dramatically altered distal lung morphology and exhibited significant physiological alterations, notably, increased lung elastance. The changes in distal lung …

Effects Of Perinatal Oxycodone Exposure On The Cardiovascular Response To Acute Stress In Male Rats At Weaning And In Young Adulthood, Thitinart Sithisarn, Henrietta S. Bada, Richard J. Charnigo, Sandra J. Legan, David C. Randall

Pediatrics Faculty Publications

Oxycodone (OXY) is one of the most commonly abused opiates during pregnancy. Perinatal opiate exposure (POE) is associated with neurobehavioral and hormone changes. Little is known about the effects of perinatal OXY on the cardiovascular (CV) responses to stress.

Objectives: to determine the effects of POE on: (1) CV responses to acute stress and ability to discriminate using a classical conditioning paradigm; (2) changes in CV response to the paradigm and retention of the ability to discriminate from postnatal day (PD) 40 to young adulthood.

Methods: Pregnant rats were given i.v. OXY or vehicle (CON) daily. OXY and CON males …

Pharmacology And Clinical Potential Of Guanylyl Cyclase C Agonists In The Treatment Of Ulcerative Colitis., Giovanni M Pitari

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Agonists of the transmembrane intestinal receptor guanylyl cyclase C (GCC) have recently attracted interest as promising human therapeutics. Peptide ligands that can specifically induce GCC signaling in the intestine include endogenous hormones guanylin and uroguanylin, diarrheagenic bacterial enterotoxins (ST), and synthetic drugs linaclotide, plecanatide, and SP-333. These agonists bind to GCC at intestinal epithelial surfaces and activate the receptor's intracellular catalytic domain, an event initiating discrete biological responses upon conversion of guanosine-5'-triphosphate to cyclic guanosine monophosphate. A principal action of GCC agonists in the colon is the promotion of mucosal homeostasis and its dependent barrier function. Herein, GCC agonists are …

Holobiont Nutrition: Considering The Role Of The Gastrointestinal Microbiota In The Health Benefits Of Whole Grains, Jens Walter, Ines Martinez, Devin J. Rose

Food for Health: Publications

Intake of whole grains and other food products high in dietary fiber have long been linked to the prevention of chronic diseases associated with inflammation. A contribution of the gastrointestinal microbiota to these effects has been suggested, but little is known on how whole grains interact with gut bacteria. We have recently published the first human trial that made use of next-generation sequencing to determine the effect of whole grains (whole grain barley, brown rice or a mixture of the two) on fecal microbiota structure and tested for associations between the gut microbiota and blood markers of inflammation, glucose and …

Alcohol And The Heart: To Abstain Or Not To Abstain?, Rajesh Movva, Md, Mrcp, Vincent M. Figueredo, M.D.

Division of Cardiology Faculty Papers

Alcohol has been consumed by most societies over the last 7000 years. Abraham Lincoln said "It has long been recognized that the problems with alcohol relate not to the use of a bad thing, but to the abuse of a good thing." Light to moderate alcohol consumption reduces the incidence of coronary heart disease (CHD), ischemic stroke, peripheral arterial disease, CHD mortality, and all-cause mortality, especially in the western populations. However, heavy alcohol consumption is detrimental causing cardiomyopathy, cardiac arrhythmias, hepatic cirrhosis, pancreatitis, and hemorrhagic stroke. In this article, we review the effects of alcohol on CHD, individual cardiovascular risk …

Smooth Muscle Fascicular Reorientation Is Required For Esophageal Morphogenesis And Dependent On Cdo., Anthony I Romer, Jagmohan Singh, Satish Rattan, Robert S Krauss

Department of Medicine Faculty Papers

Postnatal maturation of esophageal musculature involves proximal-to-distal replacement of smooth muscle with skeletal muscle by elusive mechanisms. We report that this process is impaired in mice lacking the cell surface receptor Cdo and identify the underlying developmental mechanism. A myogenic transition zone containing proliferative skeletal muscle precursor cells migrated in a proximal-distal direction, leaving differentiated myofibers in its wake. Distal to the transition zone, smooth muscle fascicles underwent a morphogenetic process whereby they changed their orientation relative to each other and to the lumen. Consequently, a path was cleared for the transition zone, and smooth muscle ultimately occupied only the …

Caveolar Fatty Acids And Acylation Of Caveolin-1, Qian Cai, Ling Guo, Haiqing Gao, Xiang-An Li

Pediatrics Faculty Publications

PURPOSE: Caveolae are cholesterol and sphingolipids rich subcellular domains on plasma membrane. Caveolae contain a variety of signaling proteins which provide platforms for signaling transduction. In addition to enriched with cholesterol and sphingolipids, caveolae also contain a variety of fatty acids. It has been well-established that acylation of protein plays a pivotal role in subcellular location including targeting to caveolae. However, the fatty acid compositions of caveolae and the type of acylation of caveolar proteins remain largely unknown. In this study, we investigated the fatty acids in caveolae and caveolin-1 bound fatty acids.

METHODS: Caveolae were isolated from Chinese hamster …

Comparison Study Of Airway Reactivity Outcomes Due To A Pharmacologic Challenge Test: Impulse Oscillometry Versus Least Mean Squared Analysis Techniques., Elena Rodriguez, Charrell M Bullard, Milena H Armani, Thomas L Miller, Thomas H Shaffer

Department of Medicine Faculty Papers

The technique of measuring transpulmonary pressure and respiratory airflow with manometry and pneumotachography using the least mean squared analysis (LMS) has been used broadly in both preclinical and clinical settings for the evaluation of neonatal respiratory function during tidal volume breathing for lung tissue and airway frictional mechanical properties measurements. Whereas the technique of measuring respiratory function using the impulse oscillation technique (IOS) involves the assessment of the relationship between pressure and flow using an impulse signal with a range of frequencies, requires less cooperation and provides more information on total respiratory system resistance (chest wall, lung tissue, and airways). …

A Review Of Nutritional Factors In Hypertension Management., Ha Nguyen, Olaide A Odelola, Janani Rangaswami, Aman Amanullah

Department of Medicine Faculty Papers

Hypertension is a major health problem worldwide. Its attendant morbidity and mortality complications have a great impact on patient's quality of life and survival. Optimizing blood pressure control has been shown to improve overall health outcomes. In addition to pharmacological therapies, nonpharmacological approach such as dietary modification plays an important role in controlling blood pressure. Many dietary components such as sodium, potassium, calcium, and magnesium have been studied substantially in the past decades. While some of these nutrients have clear evidence for their recommendation, some remain controversial and are still of ongoing study. Dietary modification is often discussed with patients …

Hyper-Arousal Decreases Human Visual Thresholds, Adam J. Woods, John W. Philbeck, Philip Wirtz

Neurological Surgery Faculty Publications

Arousal has long been known to influence behavior and serves as an underlying component of cognition and consciousness. However, the consequences of hyper-arousal for visual perception remain unclear. The present study evaluates the impact of hyper-arousal on two aspects of visual sensitivity: visual stereoacuity and contrast thresholds. Sixty-eight participants participated in two experiments. Thirty-four participants were randomly divided into two groups in each experiment: Arousal Stimulation or Sham Control. The Arousal Stimulation group underwent a 50-second cold pressor stimulation (immersing the foot in 0–2° C water), a technique known to increase arousal. In contrast, the Sham Control group immersed their …

Bortezomib (Ps-341) Treatment Decreases Inflammation And Partially Rescues The Expression Of The Dystrophin-Glycoprotein Complex In Grmd Dogs., Karla P C Araujo, Gloria Bonuccelli, Caio N Duarte, Thais P Gaiad, Dayson F Moreira, David Feder, José E Belizario, Maria A Miglino, Michael P Lisanti, Carlos E Ambrosio

Department of Stem Cell Biology and Regenerative Medicine Faculty Papers & Presentations

Golden retriever muscular dystrophy (GRMD) is a genetic myopathy corresponding to Duchenne muscular dystrophy (DMD) in humans. Muscle atrophy is known to be associated with degradation of the dystrophin-glycoprotein complex (DGC) via the ubiquitin-proteasome pathway. In the present study, we investigated the effect of bortezomib treatment on the muscle fibers of GRMD dogs. Five GRMD dogs were examined; two were treated (TD- Treated dogs) with the proteasome inhibitor bortezomib, and three were control dogs (CD). Dogs were treated with bortezomib using the same treatment regimen used for multiple myeloma. Pharmacodynamics were evaluated by measuring the inhibition of 20S proteasome activity …

Early Prediction Of Trauma Patient Discharge Disposition, Ronald Beaulieu, Priti Parikh, Akpofure Peter Ekeh, Ronald J. Markert, Mary C. Mccarthy

Department of Surgery Faculty Publications

Objective: Do pre-injury and early hospital admission characteristics help predict patient discharge disposition? Background: Total one-year treatment cost of adult major trauma in the United States is estimated at $30 billion annually, with 58% of the cost due to the index hospitalization. Increased length of stay (LOS) increases morbidity and delays rehabilitation. Prediction of discharge to a location other than home through univariate risk factor methodology and development of a multivariable binary logistic regression model allows early discharge planning. Methods: A one-year Level 1 trauma center registry dataset was used to develop a predictive model of discharge disposition using 2836 …

Glucose Stimulation Induces Dynamic Change Of Mitochondrial Morphology To Promote Insulin Secretion In The Insulinoma Cell Line Ins-1e., Bong Sook Jhun, Hakjoo Lee, Zheng-Gen Jin, Yisang Yoon

Center for Translational Medicine Faculty Papers

Fission and fusion of mitochondrial tubules are the major processes regulating mitochondrial morphology. However, the physiological significance of mitochondrial shape change is poorly understood. Glucose-stimulated insulin secretion (GSIS) in pancreatic β-cells requires mitochondrial ATP production which evokes Ca(2+) influx through plasma membrane depolarization, triggering insulin vesicle exocytosis. Therefore, GSIS reflects mitochondrial function and can be used for evaluating functional changes associated with morphological alterations of mitochondria. Using the insulin-secreting cell line INS-1E, we found that glucose stimulation induced rapid mitochondrial shortening and recovery. Inhibition of mitochondrial fission through expression of the dominant-negative mutant DLP1-K38A eliminated this dynamic mitochondrial shape change …

Glucose Stimulation Induces Dynamic Change Of Mitochondrial Morphology To Promote Insulin Secretion In The Insulinoma Cell Line Ins-1e., Bong Sook Jhun, Hakjoo Lee, Zheng-Gen Jin, Yisang Yoon

Center for Translational Medicine Faculty Papers

Fission and fusion of mitochondrial tubules are the major processes regulating mitochondrial morphology. However, the physiological significance of mitochondrial shape change is poorly understood. Glucose-stimulated insulin secretion (GSIS) in pancreatic β-cells requires mitochondrial ATP production which evokes Ca(2+) influx through plasma membrane depolarization, triggering insulin vesicle exocytosis. Therefore, GSIS reflects mitochondrial function and can be used for evaluating functional changes associated with morphological alterations of mitochondria. Using the insulin-secreting cell line INS-1E, we found that glucose stimulation induced rapid mitochondrial shortening and recovery. Inhibition of mitochondrial fission through expression of the dominant-negative mutant DLP1-K38A eliminated this dynamic mitochondrial shape change …

The Effect Of Network Transitions On Spontaneous Activity And Sycnhrony In Devloping Neural Networks, Jude P. J. Savarraj

Doctoral Dissertations

Connectivity patterns of developing neural circuits and the effects of its dynamics on network behavior, particularly the emergence of spontaneous activity and synchrony, are not clear. We attempt to quantify anatomical connectivity patterns of rat cortical cultures during different stages of development. By culturing the networks on dishes embedded with micro electrode arrays, we simultaneously record electrical activity from multiple regions of the developing network and monitor its electrical behavior, particularly its tendency to fire spontaneously and to synchronize under certain conditions. We investigate possible correlations between changes in the network connectivity patterns and spontaneous electrical activity and synchrony. Cocultures …

The Tweak Receptor Fn14 Is A Therapeutic Target In Melanoma: Immunotoxins Targeting Fn14 Receptor For Malignant Melanoma Treatment., Hong Zhou, Suhendan Ekmekcioglu, John W Marks, Khalid A Mohamedali, Kaushal Asrani, Keeley K Phillips, Sharron A N Brown, Emily Cheng, Michele B Weiss, Walter N Hittelman, Nhan L Tran, Hideo Yagita, Jeffrey A Winkles, Michael G Rosenblum

Department of Cancer Biology Faculty Papers

Fibroblast growth factor-inducible protein 14 (Fn14), the cell surface receptor for tumor necrosis factor-like weak inducer of apoptosis (TWEAK), is overexpressed in various human solid tumor types and can be a negative prognostic indicator. We detected Fn14 expression in ∼60% of the melanoma cell lines we tested, including both B-Raf WT and B-Raf(V600E) lines. Tumor tissue microarray analysis indicated that Fn14 expression was low in normal skin, but elevated in 173/190 (92%) of primary melanoma specimens and in 86/150 (58%) of melanoma metastases tested. We generated both a chemical conjugate composed of the recombinant gelonin (rGel) toxin and the anti-Fn14 …

Perception Of Disease Risk And Vulnerability As A Function Of Proximity To National Park Boundaries In East Africa, Irene Bridget Feretti

Honors Theses and Capstones

Studies suggest households closest to parks and protected areas (PAs) are more likely to sustain park-related losses, but the relationship between human sickness and PAs has not been fully explored. Existing literature primarily focuses on human-wildlife conflicts (i.e. crop raiding) and the potential for zoonotic disease spillover and emergence at the human-livestock-wildlife interface at PA boundaries. Understanding local perceptions of disease risk and vulnerability is essential for assessing human health relative to conservation areas. This understanding will promote better-informed consideration of human health impacts in decision making for conservation. Data from surveys taken at 301 households around Kibale National Park …

Neuroinflammation And Psychiatric Illness, Souhel Najjar, Daniel M. Pearlman, Kenneth Alper, Amanda Najjar, Orrin Devinsky

Dartmouth Scholarship

Multiple lines of evidence support the pathogenic role of neuroinflammation in psychiatric illness. While systemic autoimmune diseases are well-documented causes of neuropsychiatric disorders, synaptic autoimmune encephalitides with psychotic symptoms often go under-recognized. Parallel to the link between psychiatric symptoms and autoimmunity in autoimmune diseases, neuroimmunological abnormalities occur in classical psychiatric disorders (for example, major depressive, bipolar, schizophrenia, and obsessive-compulsive disorders). Investigations into the pathophysiology of these conditions traditionally stressed dysregulation of the glutamatergic and monoaminergic systems, but the mechanisms causing these neurotransmitter abnormalities remained elusive. We review the link between autoimmunity and neuropsychiatric disorders, and the human and experimental evidence …

Intra-Tumoral Heterogeneity In Metastatic Potential And Survival Signaling Between Iso-Clonal Hct116 And Hct116b Human Colon Carcinoma Cell Lines., Sanjib Chowdhury, Melanie Ongchin, Elizabeth Sharratt, Ivan Dominguez, J. Wang, Michael G. Brattain, Ashwani Rajput

Journal Articles: Eppley Institute

BACKGROUND: Colorectal cancer (CRC) metastasis is a leading cause of cancer-related deaths in the United States. The molecular mechanisms underlying this complex, multi-step pathway are yet to be completely elucidated. Recent reports have stressed the importance of intra-tumoral heterogeneity in the development of a metastatic phenotype. The purpose of this study was to characterize the intra-tumoral phenotypic heterogeneity between two iso-clonal human colon cancer sublines HCT116 and HCT116b on their ability to undergo metastatic colonization and survive under growth factor deprivation stress (GFDS).

MATERIALS AND METHODS: HCT116 and HCT116b cells were transfected with green fluorescence protein and subcutaneously injected into …

The Ccl5/Ccr5 Axis Promotes Metastasis In Basal Breast Cancer., Marco Velasco-Velázquez, Richard G Pestell

Kimmel Cancer Center Faculty Papers

Recently, we have shown that the CCL5/CCR5 axis is active in patients affected by an aggressive basal subtype of breast cancer. Using preclinical models, we have demonstrated that CCR5 promotes breast cancer invasiveness and metastatic potential, while CCR5 inhibition abrogates them. Thus, CCR5 antagonists may constitute an alternative therapeutic approach for patients affected by metastatic basal breast cancer.

Study Of The Insulin Mimetic Sodium Orthovanadate In Glucosamine Induced Insulin Resistnace In Primary Rat Hepatocytes, Kalan Mcpherson

Masters Theses

Insulin resistance and type II diabetes is a disease state characterized by a lack of sensitivity of insulin to provoke a proper response in insulin sensitive tissues. Currently, we utilize glucosamine to increase flux through the Hexosamine Biosynthetic Pathway (HBP) to induce an insulin resistance like state in primary rat hepatocytes. We tested the effectiveness of the insulin mimetic sodium orthovanadate to determine if it could elicit an insulin-like response under these conditions. Mixed results were obtained on the effectiveness of vanadate as an insulin mimetic in this insulin resistant model.

Frequency Of Precancerous Lesions In Endoscopic Gastric Biopsies In Chronic Gastritis, Saroona Haroon, Naveen Faridi, Faisal Rashid Lodhi, Shafaq Mujtaba

Department of Pathology and Laboratory Medicine

Objective:
To determine the frequency of precancerous lesions in endoscopic gastric biopsies of patients with chronic gastritis.STUDY Design: A case series.
Place and duration of study:
Department of Histopathology, Liaquat National Hospital, Karachi, from July 2008 to January 2009.METHODOLOGY: Over 6 months, 375 endoscopic gastric biopsies of patients with age group of 15-65 years having endoscopic chronic gastritis were included. From final biopsy report, basic information like patient demographics and presence of precancerous lesions i.e. activity (chronic active gastritis), atrophy (atrophic gastritis), intestinal metaplasia and dysplasia were recorded on proforma. Results were described as proportions and frequency.
Results:
The frequency …

Intracranial Injection Of Aav Expressing Nep But Not Ide Reduces Amyloid Pathology In App+Ps1 Transgenic Mice, Nikisha Carty, Kevin R. Nash, Milene Brownlow, Dana Cruite, Donna M. Wilcock, Maj-Linda B. Selenica, Daniel C. Lee, Marcia N. Gordon, Dave Morgan

Sanders-Brown Center on Aging Faculty Publications

The accumulation of β-amyloid peptides in the brain has been recognized as an essential factor in Alzheimer's disease pathology. Several proteases, including Neprilysin (NEP), endothelin converting enzyme (ECE), and insulin degrading enzyme (IDE), have been shown to cleave β-amyloid peptides (Aβ). We have previously reported reductions in amyloid in APP+PS1 mice with increased expression of ECE. In this study we compared the vector-induced increased expression of NEP and IDE. We used recombinant adeno-associated viral vectors expressing either native forms of NEP (NEP-n) or IDE (IDE-n), or engineered secreted forms of NEP (NEP-s) or IDE (IDE-s). In a six-week study, immunohistochemistry …

Bapineuzumab Alters Aβ Composition: Implications For The Amyloid Cascade Hypothesis And Anti-Amyloid Immunotherapy, Alex E. Roher, David H. Cribbs, Ronald C. Kim, Chera L. Maarouf, Charisse M. Whiteside, Tyler A. Kokjohn, Ian D. Daugs, Elizabeth Head, Carolyn Liebsack, Geidy Serrano, Christine Belden, Marwan N. Sabbagh, Thomas G. Beach

Sanders-Brown Center on Aging Faculty Publications

The characteristic neuropathological changes associated with Alzheimer's disease (AD) and other lines of evidence support the amyloid cascade hypothesis. Viewing amyloid deposits as the prime instigator of dementia has now led to clinical trials of multiple strategies to remove or prevent their formation. We performed neuropathological and biochemical assessments of 3 subjects treated with bapineuzumab infusions. Histological analyses were conducted to quantify amyloid plaque densities, Braak stages and the extent of cerebral amyloid angiopathy (CAA). Amyloid-β (Aβ) species in frontal and temporal lobe samples were quantified by ELISA. Western blots of amyloid-β precursor protein (AβPP) and its C-terminal (CT) fragments …