Medicine and Health Sciences Commons^™

Cellular Responses And Tissue Depots For Nanoformulated Antiretroviral Therapy., Andrea L. Martinez-Skinner, Mariluz Araínga, Pavan Puligujja, Diana L. Palandri, Hannah M. Baldridge, Benson J. Edagwa, Joellyn Mcmillan, R. Lee Mosley, Howard Gendelman

Journal Articles: Pharmacology & Experimental Neuroscience

Long-acting nanoformulated antiretroviral therapy (nanoART) induces a range of innate immune migratory, phagocytic and secretory cell functions that perpetuate drug depots. While recycling endosomes serve as the macrophage subcellular depots, little is known of the dynamics of nanoART-cell interactions. To this end, we assessed temporal leukocyte responses, drug uptake and distribution following both intraperitoneal and intramuscular injection of nanoformulated atazanavir (nanoATV). Local inflammatory responses heralded drug distribution to peritoneal cell populations, regional lymph nodes, spleen and liver. This proceeded for three days in male Balb/c mice. NanoATV-induced changes in myeloid populations were assessed by fluorescence-activated cell sorting (FACS) with CD45, …

Cellular Responses And Tissue Depots For Nanoformulated Antiretroviral Therapy., Andrea L. Martinez-Skinner, Mariluz Araínga, Pavan Puligujja, Diana L. Palandri, Hannah M. Baldridge, Benson J. Edagwa, Joellyn Mcmillan, R. Lee Mosley, Howard Gendelman

Journal Articles: Pharmacology & Experimental Neuroscience

Long-acting nanoformulated antiretroviral therapy (nanoART) induces a range of innate immune migratory, phagocytic and secretory cell functions that perpetuate drug depots. While recycling endosomes serve as the macrophage subcellular depots, little is known of the dynamics of nanoART-cell interactions. To this end, we assessed temporal leukocyte responses, drug uptake and distribution following both intraperitoneal and intramuscular injection of nanoformulated atazanavir (nanoATV). Local inflammatory responses heralded drug distribution to peritoneal cell populations, regional lymph nodes, spleen and liver. This proceeded for three days in male Balb/c mice. NanoATV-induced changes in myeloid populations were assessed by fluorescence-activated cell sorting (FACS) with CD45, …

Selective Vip Receptor Agonists Facilitate Immune Transformation For Dopaminergic Neuroprotection In Mptp-Intoxicated Mice., Katherine E. Olson, Lisa M. Kosloski-Bilek, Kristi M. Anderson, Breha J. Diggs, Barbara E. Clark, John M. Gledhill, Scott J. Shandler, R. Lee Mosley, Howard Gendelman

Journal Articles: Pharmacology & Experimental Neuroscience

UNLABELLED: Vasoactive intestinal peptide (VIP) mediates a broad range of biological responses by activating two related receptors, VIP receptor 1 and 2 (VIPR1 and VIPR2). Although the use of native VIP facilitates neuroprotection, clinical application of the hormone is limited due to VIP's rapid metabolism and inability to distinguish between VIPR1 and VIPR2 receptors. In addition, activation of both receptors by therapeutics may increase adverse secondary toxicities. Therefore, we developed metabolically stable and receptor-selective agonists for VIPR1 and VIPR2 to improve pharmacokinetic and pharmacodynamic therapeutic end points. Selective agonists were investigated for their abilities to protect mice against MPTP-induced neurodegeneration …

Vanishing Retinal Arterial Aneurysms With Anti-Tubercular Treatment In A Patient Presenting With Idiopathic Retinal Vasculitis, Aneurysms, And Neuroretinitis., Ramandeep Singh, Kusum Sharma, Aniruddha Agarwal, Mohit Dogra, Vishali Gupta, Aman Sharma, Mangat R. Dogra

Journal Articles: Ophthalmology

BACKGROUND: Idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) syndrome presents with characteristic clinical manifestations such as aneurysms at arteriolar bifurcations and optic nerve and retinal vascular inflammation. Regression of such features on treatment with anti-tubercular therapy (ATT) combined with corticosteroids has not been reported in literature.

FINDINGS: A 30-year-old female with sudden painless decreased vision in the left eye was referred with a diagnosis of presumed tuberculous retinal vasculitis and a positive tuberculin skin test. Based on the clinical and angiographic features of the right eye, a diagnosis of IRVAN syndrome was made. In the left eye, the patient had …

Silibinin-Mediated Metabolic Reprogramming Attenuates Pancreatic Cancer-Induced Cachexia And Tumor Growth., Surendra K. Shukla, Aneesha Dasgupta, Kamiya Mehla, Venugopal Gunda, Enza Vernucci, Joshua J. Souchek, Gennifer Goode, Ryan King, Anusha Mishra, Ibha Rai, Sangeetha Nagarajan, Nina V. Chaika, Fang Yu, Surendra K. Shukla

Journal Articles: Eppley Institute

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related deaths in the US. Cancer-associated cachexia is present in up to 80% of PDAC patients and is associated with aggressive disease and poor prognosis. In the present studies we evaluated an anti-cancer natural product silibinin for its effectiveness in targeting pancreatic cancer aggressiveness and the cachectic properties of pancreatic cancer cells and tumors. Our results demonstrate that silibinin inhibits pancreatic cancer cell growth in a dose-dependent manner and reduces glycolytic activity of cancer cells. Our LC-MS/MS based metabolomics data demonstrates that silibinin treatment induces global metabolic reprogramming in pancreatic …

Combined Systemic And Ocular Chemotherapy For Anterior Segment Metastasis Of Systemic Mantle Cell Lymphoma., Aniruddha Agarwal, Mohammad Ali Sadiq, William R. Rhoades, Loren S. Jack, Mostafa Hanout, Philip J. Bierman, William W. West, Quan Dong Nguyen

Journal Articles: Ophthalmology

BACKGROUND: Mantle cell lymphoma (MCL) is an aggressive subtype of non-Hodgkin's lymphoma that rarely metastasizes to the iris and the anterior segment. Blastic/pleomorphic morphology is thought to have an adverse effect on prognosis in MCL. MCL is resistant to conventional chemotherapeutic regimens with a tendency for multiple relapses. Management of anterior segment metastasis of systemic MCL has not been described in literature.

FINDINGS: A 58-year-old male presented with an aggressive, relapsing, metastatic, systemic blastic variant of MCL with ocular involvement. At the time of initial presentation, large tumor cells were visible in the anterior chamber (AC) along with hypopyon and …

Outcomes With As-Needed Ranibizumab After Initial Monthly Therapy: Long-Term Outcomes Of The Phase Iii Ride And Rise Trials., David S. Boyer, Quan Dong Nguyen, David M. Brown, Karen Basu, Jason S. Ehrlich

Journal Articles: Ophthalmology

PURPOSE: To determine whether the efficacy and safety achieved with monthly ranibizumab as treatment for diabetic macular edema (DME) can be maintained with less-than-monthly treatment.

DESIGN: Open-label extension (OLE) phase of randomized, sham-controlled phase III trials: RIDE (NCT00473382) and RISE (NCT00473330).

PARTICIPANTS: Five hundred of 582 adults who completed the 36-month randomized core studies elected to enter the OLE.

METHODS: All patients participating in the OLE were eligible to receive 0.5 mg ranibizumab according to predefined re-treatment criteria: Treatment was administered when DME was identified by the investigator on optical coherence tomography or when best-corrected visual acuity (BCVA) worsened by …

Enormous, Rapidly Growing Breast Mass., Vivek Verma, Sanjay Muttineni, Rajesh R. Kulkarni, Edibaldo Silva, William W. West, Robert B. Thompson

Journal Articles: Oncology and Hematology

BACKGROUND: Signs and symptoms of a rapidly enlarging breast mass are not only important for all clinicians to recognize and assess, but also are not uncommon occurrences. We describe a similar but unique case that developed into an enormous, 36 cm exophytic mass.

CASE PRESENTATION: A 51-year-old woman with history of psychiatric conditions presented for signs and symptoms of sepsis. It was determined that the source was an enormous 36 cm mass originating from the breast/chest wall. After stabilizing the patient with antibiotics, she underwent successful resection. Surgical margins were positive, and histopathology demonstrated bland spindle cells with stromal overgrowth. …

Role Of Micrornas In Alcohol-Induced Multi-Organ Injury., Sathish Kumar Natarajan, Joseph M. Pachunka, Justin L. Mott

Journal Articles: Biochemistry & Molecular Biology

Alcohol consumption and its abuse is a major health problem resulting in significant healthcare cost in the United States. Chronic alcoholism results in damage to most of the vital organs in the human body. Among the alcohol-induced injuries, alcoholic liver disease is one of the most prevalent in the United States. Remarkably, ethanol alters expression of a wide variety of microRNAs that can regulate alcohol-induced complications or dysfunctions. In this review, we will discuss the role of microRNAs in alcoholic pancreatitis, alcohol-induced liver damage, intestinal epithelial barrier dysfunction, and brain damage including altered hippocampus structure and function, and neuronal loss, …

Active Yap Promotes Pancreatic Cancer Cell Motility, Invasion And Tumorigenesis In A Mitotic Phosphorylation-Dependent Manner Through Lpar3., Shuping Yang, Lin Zhang, Vinee Purohit, Surendra K. Shukla, Xingcheng Chen, Fang Yu, Kai Fu, Yuanhong Chen, Joyce C. Solheim, Surendra K. Shukla, Wei Song, Jixin Dong

Journal Articles: Eppley Institute

The transcriptional co-activator Yes-associated protein, YAP, is a main effector in the Hippo tumor suppressor pathway. We recently defined a mechanism for positive regulation of YAP through CDK1-mediated mitotic phosphorylation. Here, we show that active YAP promotes pancreatic cancer cell migration, invasion and anchorage-independent growth in a mitotic phosphorylation-dependent manner. Mitotic phosphorylation is essential for YAP-driven tumorigenesis in animals. YAP reduction significantly impairs cell migration and invasion. Immunohistochemistry shows significant upregulation and nuclear localization of YAP in metastases when compared with primary tumors and normal tissue in human. Mitotic phosphorylation of YAP controls a unique transcriptional program in pancreatic cells. …

Endogenous Endophthalmitis: Diagnosis, Management, And Prognosis., Mohammad Ali Sadiq, Muhammad Hassan, Aniruddha Agarwal, Salman Sarwar, Shafak Toufeeq, Mohamed K. Soliman, Mostafa Hanout, Yasir Jamal Sepah, Diana V. Do, Quan Dong Nguyen

Journal Articles: Ophthalmology

Endogenous endophthalmitis is an ophthalmic emergency that can have severe sight-threatening complications. It is often a diagnostic challenge because it can manifest at any age and is associated with a number of underlying predisposing factors. Microorganisms associated with this condition vary along a broad spectrum. Depending upon the severity of the disease, both medical and surgical interventions may be employed. Due to rarity of the disease, there are no guidelines in literature for optimal management of these patients. In this review, treatment guidelines based on clinical data and microorganism profile have been proposed.

Bdnf Contributes To Angiotensin Ii-Mediated Reductions In Peak Voltage-Gated K+ Current In Cultured Cath.A Cells., Bryan K. Becker, Han-Jun Wang, Changhai Tian, Irving H. Zucker

Journal Articles: Cellular & Integrative Physiology

Increased central angiotensin II (Ang II) levels contribute to sympathoexcitation in cardiovascular disease states such as chronic heart failure and hypertension. One mechanism by which Ang II increases neuronal excitability is through a decrease in voltage-gated, rapidly inactivating K(+) current (IA); however, little is known about how Ang II signaling results in reduced IA. Brain-derived neurotrophic factor (BDNF) has also been demonstrated to decrease IA and has signaling components common to Ang II. Therefore, we hypothesized that Ang II-mediated suppression of voltage-gated K(+) currents is due, in part, to BDNF signaling. Differentiated CATH.a, catecholaminergic cell line treated with BDNF for …

Neuroinflammatory Paradigms In Lysosomal Storage Diseases., Megan Bosch, Tammy Kielian

Journal Articles: Pathology and Microbiology

Lysosomal storage diseases (LSDs) include approximately 70 distinct disorders that collectively account for 14% of all inherited metabolic diseases. LSDs are caused by mutations in various enzymes/proteins that disrupt lysosomal function, which impairs macromolecule degradation following endosome-lysosome and phagosome-lysosome fusion and autophagy, ultimately disrupting cellular homeostasis. LSDs are pathologically typified by lysosomal inclusions composed of a heterogeneous mixture of various proteins and lipids that can be found throughout the body. However, in many cases the CNS is dramatically affected, which may result from heightened neuronal vulnerability based on their post-mitotic state. Besides intrinsic neuronal defects, another emerging factor common to …

Apobec3g Interacts With Ssdna By Two Modes: Afm Studies., Luda S. Shlyakhtenko, Samrat Dutta, Jaspreet Banga, Ming Li, Reuben S. Harris, Yuri L. Lyubchenko

Journal Articles: Pharmaceutical Sciences

APOBEC3G (A3G) protein has antiviral activity against HIV and other pathogenic retroviruses. A3G has two domains: a catalytic C-terminal domain (CTD) that deaminates cytidine, and a N-terminal domain (NTD) that binds to ssDNA. Although abundant information exists about the biological activities of A3G protein, the interplay between sequence specific deaminase activity and A3G binding to ssDNA remains controversial. We used the topographic imaging and force spectroscopy modalities of Atomic Force Spectroscopy (AFM) to characterize the interaction of A3G protein with deaminase specific and nonspecific ssDNA substrates. AFM imaging demonstrated that A3G has elevated affinity for deaminase specific ssDNA than for …

Mortality-Related Resource Utilization In The Inpatient Care Of Hypoplastic Left Heart Syndrome., David A. Danford, Quentin Karels, Aparna Kulkarni, Aysha Hussain, Yunbin Xiao, Shelby Kutty

Journal Articles: Pediatrics

BACKGROUND: Quantifying resource utilization in the inpatient care of congenital heart diease is clinically relevant. Our purpose is to measure the investment of inpatient care resources to achieve survival in hypoplastic left heart syndrome (HLHS), and to determine how much of that investment occurs in hospitalizations that have a fatal outcome, the mortality-related resource utilization fraction (MRRUF).

METHODS: A collaborative administrative database, the Pediatric Health Information System (PHIS) containing data for 43 children's hospitals, was queried by primary diagnosis for HLHS admissions of patients ≤21 years old during 2004-2013. Institution, patient age, inpatient deaths, billed charges (BC) and length of …

Naturally Occurring Deletion Mutants Of The Pig-Specific, Intestinal Crypt Epithelial Cell Protein Clca4b Without Apparent Phenotype., Stephanie Plog, Nikolai Klymiuk, Stefanie Binder, Matthew J. Van Hook, Wallace B. Thoreson, Achim D. Gruber, Lars Mundhenk

Journal Articles: Ophthalmology

The human CLCA4 (chloride channel regulator, calcium-activated) modulates the intestinal phenotype of cystic fibrosis (CF) patients via an as yet unknown pathway. With the generation of new porcine CF models, species-specific differences between human modifiers of CF and their porcine orthologs are considered critical for the translation of experimental data. Specifically, the porcine ortholog to the human CF modulator gene CLCA4 has recently been shown to be duplicated into two separate genes, CLCA4a and CLCA4b. Here, we characterize the duplication product, CLCA4b, in terms of its genomic structure, tissue and cellular expression patterns as well as its in vitro electrophysiological …

Invariant Characteristics Of Carcinogenesis., Simon Sherman, Nirosha Rathnayake, Tengiz Mdzinarishvili

Journal Articles: Eppley Institute

Carcinogenic modeling is aimed at mathematical descriptions of cancer development in aging. In this work, we assumed that a small fraction of individuals in the population is susceptible to cancer, while the rest of the population is resistant to cancer. For individuals susceptible to cancer we adopted methods of conditional survival analyses. We performed computational experiments using data on pancreatic, stomach, gallbladder, colon and rectum, liver, and esophagus cancers from the gastrointestinal system collected for men and women in the SEER registries during 1975-2009. In these experiments, we estimated the time period effects, the birth cohort effects, the age effects …

Primary Sclerosing Epithelioid Fibrosarcoma Of Kidney With Variant Histomorphologic Features: Report Of 2 Cases And Review Of The Literature., Dilek Ertoy Baydar, Kemal Kosemehmetoglu, Oguz Aydin, Julia A. Bridge, Berrin Buyukeren, Fazil Tuncay Aki

Journal Articles: Pathology and Microbiology

The authors present two cases of primary sclerosing epithelioid fibrosarcoma (SEF) of the kidney. Both patients had a mass in the upper part of the left kidney without any primary extrarenal neoplastic lesions. Grossly, the tumors were solid masses both measuring 7.5 cm in the greatest diameter. Histologically, one of the lesions exhibited a predominantly lobular growth of round or oval small uniform epithelioid cells in variable cellularity. Circular zones of crowded tumor cells alternating with hypocellular collagenous tissue in a concentric fashion around entrapped native renal tubules were distinctive. The second case was distinctive with significant cytological atypia in …

Prognostic Role Of Bnp In Children Undergoing Surgery For Congenital Heart Disease: Analysis Of Prediction Models Incorporating Standard Risk Factors., Massimiliano Cantinotti, Raffaele Giordano, Marco Scalese, Sabrina Molinaro, Francesca Della Pina, Simona Storti, Luigi Arcieri, Bruno Murzi, Marco Marotta, Vitali Pak, Vincenzo Poli, Giorgio Iervasi, Shelby Kutty, Aldo Clerico

Journal Articles: Pediatrics

BACKGROUND: The routine use of brain natriuretic peptide (BNP) in pediatric cardiac surgery remains controversial. Our aim was to test whether BNP adds information to predict risk in pediatric cardiac surgery.

METHODS: In all, 587 children undergoing cardiac surgery (median age 6.3 months; 1.2-35.9 months) were prospectively enrolled at a single institution. BNP was measured pre-operatively, on every post-operative day in the intensive care unit, and before discharge. The primary outcome was major complications and length ventilator stay >15 days. A first risk prediction model was fitted using Cox proportional hazards model with age, body surface area and Aristotle score …

Platelet Derived Growth Factor Inhibitors: A Potential Therapeutic Approach For Ocular Neovascularization., Mohammad Ali Sadiq, Mostafa Hanout, Salman Sarwar, Muhammad Hassan, Diana V. Do, Quan Dong Nguyen, Yasir Jamal Sepah

Journal Articles: Ophthalmology

Retinochoroidal vascular diseases are the leading causes of blindness in the developed world. They include diabetic retinopathy (DR), retinal vein occlusion, retinopathy of prematurity, age-related macular degeneration (AMD), and pathological myopia, among many others. Several different therapies are currently under consideration for the aforementioned disorders. In the following section, agents targeting platelet-derived growth factor (PDGF) are discussed as a potential therapeutic option for retinochoroidal vascular diseases. PDGF plays an important role in the angiogenesis cascade that is activated in retinochoroidal vascular diseases. The mechanism of action, side effects, efficacy, and the potential synergistic role of these agents in combination with …

Relevance Of The Carotid Body Chemoreflex In The Progression Of Heart Failure., David C. Andrade, Claudia Lucero, Camilo Toledo, Carlos Madrid, Noah J. Marcus, Harold D. Schultz, Rodrigo Del Rio

Journal Articles: Cellular & Integrative Physiology

Chronic heart failure (CHF) is a global health problem affecting millions of people. Autonomic dysfunction and disordered breathing patterns are commonly observed in patients with CHF, and both are strongly related to poor prognosis and high mortality risk. Tonic activation of carotid body (CB) chemoreceptors contributes to sympathoexcitation and disordered breathing patterns in experimental models of CHF. Recent studies show that ablation of the CB chemoreceptors improves autonomic function and breathing control in CHF and improves survival. These exciting findings indicate that alterations in CB function are critical to the progression of CHF. Therefore, better understanding of the physiology of …

The Hippo/Yap Pathway Interacts With Egfr Signaling And Hpv Oncoproteins To Regulate Cervical Cancer Progression., Chunbo He, Dagan Mao, Guohua Hua, Xiangmin Lv, Xingcheng Chen, Peter C. Angeletti, Jixin Dong, Steven W. Remmenga, Kerry J. Rodabaugh, Jin Zhou, Paul F. Lambert, Peixin Yang, John S. Davis, Cheng Wang

Journal Articles: Obstetrics & Gynecology

The Hippo signaling pathway controls organ size and tumorigenesis through a kinase cascade that inactivates Yes-associated protein (YAP). Here, we show that YAP plays a central role in controlling the progression of cervical cancer. Our results suggest that YAP expression is associated with a poor prognosis for cervical cancer. TGF-α and amphiregulin (AREG), via EGFR, inhibit the Hippo signaling pathway and activate YAP to induce cervical cancer cell proliferation and migration. Activated YAP allows for up-regulation of TGF-α, AREG, and EGFR, forming a positive signaling loop to drive cervical cancer cell proliferation. HPV E6 protein, a major etiological molecule of …

Effect Of Dexamethasone Prodrug On Inflamed Temporomandibular Joints In Juvenile Rats., Mitchell Knudsen, Matthew Bury, Callie Holwegner, Adam L. Reinhardt, Fang Yuan, Yijia Zhang, Peter J. Giannini, David B. Marx, Dong Wang, Richard A. Reinhardt

Journal Articles: College of Dentistry

INTRODUCTION: Juvenile idiopathic arthritis (JIA) often causes inflammation of the temporomandibular joint (TMJ) and has been treated with both systemic and intra-articular steroids, with concerns about effects on growing bones. In this study, we evaluated the impact of a macromolecular prodrug of dexamethasone (P-DEX) with inflammation-targeting potential applied systemically or directly to the TMJ.

METHODS: Joint inflammation was initiated by injecting two doses of complete Freund's adjuvant (CFA) at 1-month intervals into the right TMJs of 24 growing Sprague-Dawley male rats (controls on left side). Four additional rats were not manipulated. With the second CFA injection, animals received (1) 5 …

A Home-Based Comprehensive Care Model In Patients With Multiple Sclerosis: A Study Pre-Protocol., Lufei Young, Kathleen Healey, Mary Charlton, Kendra Schmid, Rana Zabad, Rebecca Wester

Journal Articles: College of Nursing

Background Disability is prevalent in individuals with multiple sclerosis (MS), leading to difficulty in care access, significant caregiver burden, immense challenges in self-care and great societal burden. Without highly coordinated, competent and accessible care, individuals living with progressive MS experience psychological distress, poor quality of life, suffer from life-threatening complications, and have frequent but avoidable healthcare utilizations. Unfortunately, current healthcare delivery models present severe limitations in providing easily accessible, patient-centered, coordinated comprehensive care to those with progressive MS. We propose a home-based comprehensive care model (MAHA) to address the unmet needs, challenges, and avoidable complications in individuals with progressive MS …

Myd88 In Lung Resident Cells Governs Airway Inflammatory And Pulmonary Function Responses To Organic Dust Treatment., Jill A. Poole, Todd A. Wyatt, Debra J. Romberger, Elizabeth Staab, Samantha Simet, Stephen J. Reynolds, Joseph H. Sisson, Tammy Kielian

Journal Articles: Pulmonary & Critical Care Med

Inhalation of organic dusts within agriculture environments contributes to the development and/or severity of airway diseases, including asthma and chronic bronchitis. MyD88 KO (knockout) mice are nearly completely protected against the inflammatory and bronchoconstriction effects induced by acute organic dust extract (ODE) treatments. However, the contribution of MyD88 in lung epithelial cell responses remains unclear. In the present study, we first addressed whether ODE-induced changes in epithelial cell responses were MyD88-dependent by quantitating ciliary beat frequency and cell migration following wounding by electric cell-substrate impedance sensing. We demonstrate that the normative ciliary beat slowing response to ODE is delayed in …

Cfap54 Is Required For Proper Ciliary Motility And Assembly Of The Central Pair Apparatus In Mice., Casey W. Mckenzie, Branch Craige, Tiffany V. Kroeger, Rozzy Finn, Todd A. Wyatt, Joseph H. Sisson, Jacqueline A. Pavlik, University Of Massachusetts Medical School, Gregory M. Hendricks, George B. Witman, Lance Lee

Journal Articles: Pulmonary & Critical Care Med

Motile cilia and flagella play critical roles in fluid clearance and cell motility, and dysfunction commonly results in the pediatric syndrome primary ciliary dyskinesia (PCD). CFAP221, also known as PCDP1, is required for ciliary and flagellar function in mice and Chlamydomonas reinhardtii, where it localizes to the C1d projection of the central microtubule apparatus and functions in a complex that regulates flagellar motility in a calcium-dependent manner. We demonstrate that the genes encoding the mouse homologues of the other C. reinhardtii C1d complex members are primarily expressed in motile ciliated tissues, suggesting a conserved function in mammalian motile cilia. The …

Direct Oral Anticoagulants For The Prevention Of Stroke In Patients With Nonvalvular Atrial Fibrillation: Understanding Differences And Similarities., Paul P. Dobesh, John Fanikos

Journal Articles: Pharmacy Practice

The presence of atrial fibrillation (AF), the most common sustained cardiac arrhythmia, significantly increases the risk for stroke. Current guidelines recommend that the vitamin K antagonist warfarin or direct oral anticoagulants (DOACs), such as the approved direct thrombin inhibitor dabigatran and the approved direct factor Xa inhibitors apixaban, rivaroxaban, and edoxaban, should be used for thromboprophylaxis in patients with nonvalvular AF at risk for stroke or systemic embolic events (SEE). Warfarin, the mainstay of stroke prevention in AF, increases the risk of major bleeding. Furthermore, warfarin therapy comes with several limitations including frequent monitoring and the need for dose adjustments, …

Discovering Distinct Functional Modules Of Specific Cancer Types Using Protein-Protein Interaction Networks., Ru Shen, Xiaosheng Wang, Chittibabu Guda

Journal Articles: Genetics, Cell Biology & Anatomy

Background. The molecular profiles exhibited in different cancer types are very different; hence, discovering distinct functional modules associated with specific cancer types is very important to understand the distinct functions associated with them. Protein-protein interaction networks carry vital information about molecular interactions in cellular systems, and identification of functional modules (subgraphs) in these networks is one of the most important applications of biological network analysis. Results. In this study, we developed a new graph theory based method to identify distinct functional modules from nine different cancer protein-protein interaction networks. The method is composed of three major steps: (i) extracting modules …

Identifying The Critical Domain Of Ll-37 Involved In Mediating Neutrophil Activation In The Presence Of Influenza Virus: Functional And Structural Analysis., Shweta Tripathi, Guangshun Wang, Mitchell White, Michael Rynkiewicz, Barbara Seaton, Kevan Hartshorn

Journal Articles: Pathology and Microbiology

The human cathelicidin LL-37 has been shown to play a role in host defense against influenza A viruses (IAV) through direct antiviral effects and through modulating inflammatory responses to infection. We recently showed that LL-37 increases neutrophil respiratory burst and neutrophil extracellular trap (NET) responses to IAV through engaging formyl peptide receptor 2 (FPR-2). In this paper we show that a fragment of LL-37, GI-20, which is composed of the central helical segment of the peptide, has similar effects as LL-37 on neutrophil activation. In addition to increasing respiratory burst and NET responses of the cells to IAV through an …

Staphylococcus Aureus Biofilms Induce Macrophage Dysfunction Through Leukocidin Ab And Alpha-Toxin., Tyler D. Scherr, Mark L. Hanke, Ouwen Huang, David B.A. James, Alexander R. Horswill, Kenneth W. Bayles, Paul D. Fey, Victor J. Torres, Tammy Kielian

Journal Articles: Pathology and Microbiology

UNLABELLED: The macrophage response to planktonic Staphylococcus aureus involves the induction of proinflammatory microbicidal activity. However, S. aureus biofilms can interfere with these responses in part by polarizing macrophages toward an anti-inflammatory profibrotic phenotype. Here we demonstrate that conditioned medium from mature S. aureus biofilms inhibited macrophage phagocytosis and induced cytotoxicity, suggesting the involvement of a secreted factor(s). Iterative testing found the active factor(s) to be proteinaceous and partially agr-dependent. Quantitative mass spectrometry identified alpha-toxin (Hla) and leukocidin AB (LukAB) as critical molecules secreted by S. aureus biofilms that inhibit murine macrophage phagocytosis and promote cytotoxicity. A role for Hla …