Medical Specialties Commons^™

Effect Of Tiotropium On Night-Time Awakening And Daily Rescue Medication Use In Patients With Copd, Peter M.A. Calverley, Stephen I. Rennard, Emmanuelle Clerisme-Beaty, Norbert Metzdorf, Valentina Bayer Zubek, Richard Zuwallack

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Several small studies found night-time awakenings due to COPD symptoms were associated with decreased health status. In this study, night-time awakenings in patients with COPD were examined and effects of tiotropium therapy evaluated.

METHODS: This study was a post hoc, exploratory, pooled analysis of twin, multicenter, double-blind, randomized, placebo-controlled, parallel-group trials. Patients with stable moderate-to-severe COPD were randomized to tiotropium HandiHaler® (n = 550) or placebo (n = 371) and followed for 13 weeks. During a 2-week, pre-treatment baseline period and for 13 weeks on treatment, self-reported night-time awakenings due to COPD symptoms, rescue medication (albuterol) use, and morning …

Validation Of Metabolic Alterations In Microscale Cell Culture Lysates Using Hydrophilic Interaction Liquid Chromatography (Hilic)-Tandem Mass Spectrometry-Based Metabolomics, Venugopal Gunda, Fang Yu, Pankaj K. Singh

Journal Articles: Eppley Institute

By standard convention, in order to increase the efficacy of metabolite detection from cell culture lysates, metabolite extracts from a large quantity of cells are utilized for multiple reaction monitoring-based metabolomic studies. Metabolomics from a small number of cell extracts offers a potential economical alternative to increased cell numbers, in turn increasing the utility of cell culture-based metabolomics. However, the effect of reduced cell numbers on targeted metabolomic profiling is relatively unstudied. Considering the limited knowledge available of the feasibility and accuracy of microscale cell culture metabolomics, the present study analyzes differences in metabolomic profiles of different cell numbers of …

Copd Exacerbation Biomarkers Validated Using Multiple Reaction Monitoring Mass Spectrometry, Janice M. Leung, Virginia Chen, Zsuzsanna Hollander, Darlene Dai, Scott J. Tebbutt, Shawn D. Aaron, Kathy L. Vandemheen, Stephen I. Rennard, J. Mark Fitzgerald, Prescott G. Woodruff, Stephen C. Lazarus, John E. Connett, Harvey O. Coxson, Bruce Miller, Christoph Borchers, Bruce M. Mcmanus, Raymond T. Ng, Don D. Sin

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) result in considerable morbidity and mortality. However, there are no objective biomarkers to diagnose AECOPD.

METHODS: We used multiple reaction monitoring mass spectrometry to quantify 129 distinct proteins in plasma samples from patients with COPD. This analytical approach was first performed in a biomarker cohort of patients hospitalized with AECOPD (Cohort A, n = 72). Proteins differentially expressed between AECOPD and convalescent states were chosen using a false discovery rate < 0.01 and fold change >1.2. Protein selection and classifier building were performed using an elastic net logistic regression model. The performance of the biomarker panel …

Age‐Related Changes In Cerebellar And Hypothalamic Function Accompany Non‐Microglial Immune Gene Expression, Altered Synapse Organization, And Excitatory Amino Acid Neurotransmission Deficits, Stephen J. Bonasera, Jyothi Arikkath, Michael D. Boska, Tammy R. Chaudoin, Nicholas W. Dekorver, Evan H. Goulding, Traci A. Hoke, Vahid Mojtahedzedah, Crystal D. Reyelts, Balasrinivasa R. Sajja, A. Katrin Schenk, Laurence H. Tecott, Tiffany A. Volden

Data: Geriatrics

No abstract provided.

Comparing Biocompatibility Of Ibad-Produced Nano-Films Of Titanium Oxide With Orthopaedic Grade Titanium, Raheleh Miralami

Posters and Presentations: Orthopaedic Surgery & Rehab

Titanium (Ti) is the material of choice for orthopaedic applications because it is biocompatible and encourages osteoblast growth. The present study was devised to compare the osteoblast functions on nano-crystalline titanium oxide films produced by an ion beam assisted deposition (IBAD) technique with the osteoblast functions on micro-crystalline orthopaedic-grade titanium. To characterize the biocompatibility of these surfaces, we have studied cell adhesion, growth, and differentiation on different samples. Cell responses to surfaces were examined using the human osteosarcoma cell line (SAOS-2) with osteoblastic properties. To compare cell adhesion and growth, DAPI-stained nuclei were counted using ImageJ and Metamorph software. Immunofluorescence …

Dysfunctional Epileptic Neuronal Circuits And Dysmorphic Dendritic Spines Are Mitigated By Platelet-Activating Factor Receptor Antagonism, Alberto E. Musto, Robert F. Rosencrans, Chelsey P. Walker, Surjyadipta Bhattacharjee, Chittalsinh M. Raulji, Ludmila Belayev, Zhide Fang, William C. Gordon, Nicolas G. Bazan

Journal Articles: Pediatrics

Temporal lobe epilepsy or limbic epilepsy lacks effective therapies due to a void in understanding the cellular and molecular mechanisms that set in motion aberrant neuronal network formations during the course of limbic epileptogenesis (LE). Here we show in in vivo rodent models of LE that the phospholipid mediator platelet-activating factor (PAF) increases in LE and that PAF receptor (PAF-r) ablation mitigates its progression. Synthetic PAF-r antagonists, when administered intraperitoneally in LE, re-establish hippocampal dendritic spine density and prevent formation of dysmorphic dendritic spines. Concomitantly, hippocampal interictal spikes, aberrant oscillations, and neuronal hyper-excitability, evaluated 15-16 weeks after LE using multi-array …

The Effect Of Body Mass Index On Graft Function And Kidney Transplant Outcomes, Morgan Galle

Theses & Dissertations

Background: When determining eligibility for kidney transplantation, body mass index (BMI) is often a debatable criterion for transplant due to the clinical indication, an elevated BMI has adverse effects on kidney transplant outcomes. There is a current gap in research on the effect BMI has on kidney transplant outcomes.

Purpose: The purpose of this study was to determine the role BMI plays in post-kidney transplant clinical outcomes including delayed graft function, new onset diabetes after transplant, wound complications, hospital length of stay, albumin, and readmissions to the hospital from initial hospitalization and at six months following kidney transplantation. The primary …

Evaluation Of Upper Airway Changes Following Surgical Removal Of The Adenoids Using 3-D Cone Beam Ct, Christopher C. Schultz

Theses & Dissertations

Purpose: The purpose of this study was to evaluate the changes in volume, cross-sectional area and depth of the upper airway following the surgical removal of the adenoids.

Materials and Methods: 16 patients were diagnosed with hypertrophic adenoids and referred for surgical removal. Pre-surgical and post-surgical CBCT scans were taken on each patient. Volume measurements of the total airway, oropharynx and nasopharynx were recorded. In addition, cross-sectional areas and airway depths at the posterior nasal spine (PNS) and cervical vertebrae 2 were recorded. 15 patients diagnosed with no or mild adenoid hypertrophy were treated as the control group. The controls …

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. …

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.

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 …

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 …

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 …

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 …

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 …

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 …

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 …

Ca2+ Diffusion Through Endoplasmic Reticulum Supports Elevated Intraterminal Ca2+ Levels Needed To Sustain Synaptic Release From Rods In Darkness., Minghui Chen, Matthew J. Van Hook, Wallace B. Thoreson

Journal Articles: Ophthalmology

UNLABELLED: In addition to vesicle release at synaptic ribbons, rod photoreceptors are capable of substantial slow release at non-ribbon release sites triggered by Ca(2+)-induced Ca(2+) release (CICR) from intracellular stores. To maintain CICR as rods remain depolarized in darkness, we hypothesized that Ca(2+) released into the cytoplasm from terminal endoplasmic reticulum (ER) can be replenished continuously by ions diffusing within the ER from the soma. We measured [Ca(2+)] changes in cytoplasm and ER of rods from Ambystoma tigrinum retina using various dyes. ER [Ca(2+)] changes were measured by loading ER with fluo-5N and then washing dye from the cytoplasm with …

Confident Difference Criterion: A New Bayesian Differentially Expressed Gene Selection Algorithm With Applications., Fang Yu, Ming-Hui Chen, Lynn Kuo, Heather Talbott, John S. Davis

Journal Articles: Obstetrics & Gynecology

BACKGROUND: Recently, the Bayesian method becomes more popular for analyzing high dimensional gene expression data as it allows us to borrow information across different genes and provides powerful estimators for evaluating gene expression levels. It is crucial to develop a simple but efficient gene selection algorithm for detecting differentially expressed (DE) genes based on the Bayesian estimators.

RESULTS: In this paper, by extending the two-criterion idea of Chen et al. (Chen M-H, Ibrahim JG, Chi Y-Y. A new class of mixture models for differential gene expression in DNA microarray data. J Stat Plan Inference. 2008;138:387-404), we propose two new gene …

Muc16-Mediated Activation Of Mtor And C-Myc Reprograms Pancreatic Cancer Metabolism., Surendra K. Shukla, Venugopal Gunda, Jaime Abrego, Dhanya Haridas, Anusha Mishra, Joshua J. Souchek, Nina V. Chaika, Fang Yu, Aaron R. Sasson, A Lazenby, Surinder K. Batra, Pankaj K. Singh

Journal Articles: Eppley Institute

MUC16, a transmembrane mucin, facilitates pancreatic adenocarcinoma progression and metastasis. In the current studies, we observed that MUC16 knockdown pancreatic cancer cells exhibit reduced glucose uptake and lactate secretion along with reduced migration and invasion potential, which can be restored by supplementing the culture media with lactate, an end product of aerobic glycolysis. MUC16 knockdown leads to inhibition of mTOR activity and reduced expression of its downstream target c-MYC, a key player in cellular growth, proliferation and metabolism. Ectopic expression of c-MYC in MUC16 knockdown pancreatic cancer cells restores the altered cellular physiology. Our LC-MS/MS based metabolomics studies indicate global …