Digital Commons Network^™

Xenograft Tumors Vascularized With Murine Blood Vessels May Overestimate The Effect Of Anti-Tumor Drugs: A Pilot Study, Zhihong Dong, Atsushi Imai, Sudha Krishnamurthy, Zhaocheng Zhang, Benjamin David Zeitlin, Jacques E. Nör

All Dugoni School of Dentistry Faculty Articles

Recent evidence demonstrated that endothelial cells initiate signaling events that enhance tumor cell survival, proliferation, invasion, and tumor recurrence. Under this new paradigm for cellular crosstalk within the tumor microenvironment, the origin of endothelial cells and tumor cells may have a direct impact on the pathobiology of cancer. The purpose of this pilot study was to evaluate the effect of endothelial cell species (i.e. murine or human) on xenograft tumor growth and response to therapy. Tumor xenografts vascularized either with human or with murine microvascular endothelial cells were engineered, side-by-side, subcutaneously in the dorsum of immunodefficient mice. When tumors reached …

Novel And Predominant Pathogen Responsible For The Enterovirus-Associated Encephalitis In Eastern China, Lei Zhang, Jie Yan, David M. Ojcius, Huakun Lv, Ziping Miao, Yin Chen, Yanjun Zhang, Jvying Yan

All Dugoni School of Dentistry Faculty Articles

Enteroviruses (EV) have been increasingly identified as the causative agent for unknown etiological encephalitis in many parts of the world, but the long period surveillance for enterovirus-associated encephalitis (EAE) was not reported in China. From 2002-2012 in Zhejiang, Coxsackieviruses A9, B1, B2, B3, B4, B5; and echoviruses 3, 4, 6, 9, 14, 25, 30 were detected from the unknown etiological encephalitis cases, with coxsackievirus B4 been identified here for the first time. From 2002-2004 and 2010-2012, echovirus 30 was found to be the periodically predominant serotype for in the EAE. The molecular typing results showed that all the EV isolates …

Piperazinylpyrimidine Analogues As Protein Kinase Inhibitors, Wade A. Russu, Hassan M. Shallal

Pacific Patents

The invention provides novel compounds based on piperazinylpyrimidine derivatives to be used as protein kinase inhibitors. The compounds may be useful in treating or preventing different cellular proliferation disorders, such as cancer. The present invention also provides methods of preparing these compounds, and methods of using the same.

The Gating Charge Should Not Be Estimated By Fitting A Two-State Model To A Q-V Curve, Francisco Bezanilla, Carlos A. Villalba-Galea

School of Pharmacy Faculty Articles

The voltage dependence of charges in voltage-sensitive proteins, typically displayed as charge versus voltage (Q-V) curves, is often quantified by fitting it to a simple two-state Boltzmann function. This procedure overlooks the fact that the fitted parameters, including the total charge, may be incorrect if the charge is moving in multiple steps. We present here the derivation of a general formulation for Q-V curves from multistate sequential models, including the case of infinite number of states. We demonstrate that the commonly used method to estimate the charge per molecule using a simple Boltzmann fit is not only inadequate, but in …

Minimizing Part D Costs For Medicare Beneficiaries: Not Just A Drop In The Bucket, Rajul A. Patel, Kate M. O'Dell, Kim-Anh Vo, Tiffany Chu, Kenneth Wang, Shu Lu, Joseph A. Woelfel, Sian M. Carr-Lopez, Suzanne M. Galal, Berit Gundersen

School of Pharmacy Faculty Presentations

Background: Although Medicare Part D has been largely successful in providing prescription drug coverage for Medicare beneficiaries, many continue to be burdened with unnecessary out-of-pocket (OOP) costs. Objective: This study sought to identify the frequency and impact of cost-lowering strategies used to assist Medicare beneficiaries with their Part D drug costs. Methods: Twelve outreach events were conducted in 6 different cities throughout Northern/Central California during the 2013 Medicare open enrollment period. During each event, trained student pharmacists under the supervision of licensed pharmacists assisted beneficiaries to minimize their OOP costs. Individualized assistance included: optimization of the beneficiary's Part D plan, …

Medicare Part D Prescription Drug Costs And Plan Satisfaction As A Function Of Student Pharmacists' Assistance, Rajul A. Patel, Kate M. O'Dell, Kenneth Wang, Shu Lu, Tiffany Chu, Kim-Anh Vo, Sian M. Carr-Lopez, Joseph A. Woelfel, Suzanne M. Galal, Berit Gundersen

School of Pharmacy Faculty Presentations

Background: Beneficiaries can become overwhelmed by the myriad of Medicare Part D (MPD) plans that offer prescription drug coverage. Poor choice and increased out-of-pocket (OOP) costs can be reduced through annual plan reevaluation. Objective: To examine beneficiaries' plan satisfaction and MPD drug costs as a function of prior assistance from trained student pharmacists. Methods: Twelve outreach events, nine at the same location as the previous year, were held throughout Northern/Central California during October-November 2012. Trained student pharmacists, at each event, identified the MPD plan best meeting a beneficiary's needs based on their current medications and personal preferences (e.g., preferred pharmacy). …

Sensing Charges Of The Ciona Intestinalis Voltage-Sensing Phosphatase, Carlos A. Villalba-Galea, Ludivine Frezza, Walter Sandtner, Francisco Bezanilla

School of Pharmacy Faculty Articles

Voltage control over enzymatic activity in voltage-sensitive phosphatases (VSPs) is conferred by a voltage-sensing domain (VSD) located in the N terminus. These VSDs are constituted by four putative transmembrane segments (S1 to S4) resembling those found in voltage-gated ion channels. The putative fourth segment (S4) of the VSD contains positive residues that likely function as voltage-sensing elements. To study in detail how these residues sense the plasma membrane potential, we have focused on five arginines in the S4 segment of the Ciona intestinalis VSP (Ci-VSP). After implementing a histidine scan, here we show that four arginine-to-histidine mutants, namely R223H to …

Membrane Vesicles Nucleate Mineralo-Organic Nanoparticles And Induce Carbonate Apatite Precipitation In Human Body Fluids, Cheng-Yeu Wu, Jan Martel, Wei-Yun Cheng, Chao-Chih He, David M. Ojcius, John Ding-E. Young

All Dugoni School of Dentistry Faculty Articles

Recent studies indicate that membrane vesicles (MVs) secreted by various cells are associated with human diseases, including arthritis, atherosclerosis, cancer, and chronic kidney disease. The possibility that MVs may induce the formation of mineralo-organic nanoparticles (NPs) and ectopic calcification has not been investigated so far. Here, we isolated MVs ranging in size between 20 and 400 nm from human serum and FBS using ultracentrifugation and sucrose gradient centrifugation. The MV preparations consisted of phospholipid-bound vesicles containing the serum proteins albumin, fetuin-A, and apolipoprotein A1; the mineralization-associated enzyme alkaline phosphatase; and the exosome proteins TNFR1 and CD63. Notably, we observed that …

Identification Of Leptospira Interrogans Phospholipase C As A Novel Virulence Factor Responsible For Intracellular Free Calcium Ion Elevation During Macrophage Death, Jing-Fang Zhao, Hong-Hu Chen, David M. Ojcius, Xin Zhao, Dexter Sun, Yu-Mei Ge, Lin-Li Zheng, Xu'ai Lin, Lan-Juan Li, Jie Yan

All Dugoni School of Dentistry Faculty Articles

Background: Leptospira-induced macrophage death has been confirmed to play a crucial role in pathogenesis of leptospirosis, a worldwide zoonotic infectious disease. Intracellular free Ca²⁺ concentration ([Ca²⁺]i) elevation induced by infection can cause cell death, but [Ca²⁺]i changes and high [Ca²⁺]i-induced death of macrophages due to infection of Leptospira have not been previously reported.

Methodology/Principal Findings: We first used a Ca²⁺-specific fluorescence probe to confirm that the infection of L. interrogans strain Lai triggered a significant increase of [Ca²⁺]i in mouse J774A.1 or human THP-1 macrophages. Laser confocal microscopic examination …

Pa Interactions With Law Enforcement, Jed Grant

Physician Assistant Faculty & Staff Presentations

No abstract provided.

Modulation Of The Effects Of Lung Immune Response On Bone Marrow By Oral Antigen Exposure, Pedro Xavier-Elsas, Cassio Luiz Coutinho Almeida-Da-Silva, L. Pinto, Túlio Queto, Bruno Marques Vieira, M. G. Aramha, Bianca De Luca, Daniela Masid-De-Brito, R. A. Luz, R. S. Lopes, R. Ferreira, Maria Ignez C. Gaspar-Elsas

All Dugoni School of Dentistry Faculty Articles

Allergic airway inflammation is attenuated by oral tolerization (oral exposure to allergen, followed by conventional sensitization and challenge with homologous antigen), which decreases airway allergen challenge-induced eosinophilic infiltration of the lungs and bone marrow eosinophilia. We examined its effects on bone marrow eosinophil and neutrophil production. Mice of wild type (BP-2, BALB/c, and C57BL/6) and mutant strains (lacking iNOS or CD95L) were given ovalbumin (OVA) or water (vehicle) orally and subsequently sensitized and challenged with OVA (OVA/OVA/OVA and H2O/OVA/OVA groups, resp.). Anti-OVA IgG and IgE, bone marrow eosinophil and neutrophil numbers, and eosinophil and neutrophil production ex vivo were evaluated. …

Contact Point, Arthur A. Dugoni School Of Dentistry

Contact Point

No abstract provided.

Trident - August 2013, Dugoni School Of Dentistry

Trident

The newsletter of the Pacific Orthodontic Alumni Chapter at University of the Pacific, Arthur A. Dugoni School of Dentistry.

P2x4 Assembles With P2x7 And Pannexin-1 In Gingival Epithelial Cells And Modulates Reactive Oxygen Species Production And Inflammasome Activation, Shu-Chen Hung, Chul Hee Choi, Najwane Said-Sadier, Larry Johnson, Kalina Rosenova Atanasova, Hanen Sellami, Özlem Yilmaz, David M. Ojcius

All Dugoni School of Dentistry Faculty Articles

We have previously reported that Porphyromonas gingivalis infection of gingival epithelial cells (GEC) requires an exogenous danger signal such as ATP to activate an inflammasome and caspase-1, thereby inducing secretion of interleukin (IL)-1β. Stimulation with extracellular ATP also stimulates production of reactive oxygen species (ROS) in GEC. However, the mechanism by which ROS is generated in response to ATP, and the role that different purinergic receptors may play in inflammasome activation, is still unclear. In this study, we revealed that the purinergic receptor P2X₄ is assembled with the receptor P2X₇ and its associated pore, pannexin-1. ATP induces ROS …

An Automated Procedure For Detecting Human Frequency-Following Responses To Voice Pitch, Fuh Cherng Jeng, Jiong Hu

All Faculty Scholarship

The frequency-following response (FFR) to voice pitch has been widely examined in research laboratories and has demonstrated its potential to be transformed into a useful tool for patients with hearing, speech, and language disorders in the clinic. During the past decade, many aspects of the FFR have been reported. The presence of such a response, however, still relies on subjective interpretation of the observer. Aside from a recent study reporting two algorithms for detecting such a response, there has been limited number of studies reporting the development of an automated procedure for FFR. The purpose of this study is (1) …

Influence Of Cochlear Implantation On Sentence Intelligibility And Duration, Olga Peskova, Nirmal Kumar Srinivasan, Sujin Shin, Madhu Sundarrajan, Emily Tobey

All Faculty Scholarship

Cochlear implants (CI) allow children with hearing loss (HL) to achieve speech perception and production outcomes that make their spoken speech understandable to normal hearing adult listeners. This capability is characterize by wide variability of scores. In order to understand the factors that contribute to the overall variability, we investigated the effects of duration of cochlear implantation on speech intelligibility and sentence duration over time. Participants were 107 children implanted between the ages of 2 and 4 and tested at 2 time points there they were 8 and 16 years old. Participants repeated McGarr sentences, which vary in length from …

15th Annual Pacific Research Day Abstracts, University Of The Pacific

Excellence Day

No abstract provided.

Pick1 And Ica69 Control Insulin Granule Trafficking And Their Deficiencies Lead To Impaired Glucose Tolerance, Mian Cao, Zhuo Mao, Chuen Kam, Nan (Tori) Xiao, Xiaoxing Cao, Chong Shen, Kenneth K. Y. Cheng, Aimin Xu, Kwong-Man Lee, Liwen Jiang, Jun Xia

All Dugoni School of Dentistry Faculty Articles

Diabetes is a metabolic disorder characterized by hyperglycemia. Insulin, which is secreted by pancreatic beta cells, is recognized as the critical regulator of blood glucose, but the molecular machinery responsible for insulin trafficking remains poorly defined. In particular, the roles of cytosolic factors that govern the formation and maturation of insulin granules are unclear. Here we report that PICK1 and ICA69, two cytosolic lipid-binding proteins, formed heteromeric BAR-domain complexes that associated with insulin granules at different stages of their maturation. PICK1-ICA69 heteromeric complexes associated with immature secretory granules near the trans-Golgi network (TGN). A brief treatment of Brefeldin A, which …

Contact Point, Arthur A. Dugoni School Of Dentistry

Contact Point

No abstract provided.

Alteration In Corticospinal Excitability, Talocrural Joint Range Of Motion, And Lower Extremity Function Following Manipulation In Non-Disabled Individuals, Todd E. Davenport, Stephen F. Reischl, Somporn Sungkarat, Jason Cozby, Lisa Meyer, Beth E. Fisher

School of Pharmacy Faculty Articles

Background: Clinical outcomes of manual therapy procedures, including manipulation, have been studied. However, mechanisms underlying observed improvements remain unclear.

Objective: To determine the effect of ankle joint manipulation on corticospinal excitability, ankle dorsiflexion range of motion (DF ROM), and lower extremity functional behavior in nondisabled individuals.

Method: Six nondisabled individuals (age range: 31-50 years) received the main outcomes measurements of this study, before and after long axis distraction manipulation of the talocrural joint. Main outcomes measures were motor evoked potential (MEP) amplitude of gastrocnemius (GN) and tibialis anterior (TA) using transcranial magnetic stimulation, ankle DF ROM with the knee flexed …

Hirsutella Sinensis Mycelium Suppresses Interleukin-1b And Interleukin-18 Secretion By Inhibiting Both Canonical And Non-Canonical Inflammasomes, Tsung-Teng Huang, Kowit-Yu Chong, David M. Ojcius, Yi-Hui Wu, Yun-Fei Ko, Cheng-Yeu Wu, Jan Martel, Chia-Chen Lu, Hsin-Chih Lai, John Ding-E. Young

All Dugoni School of Dentistry Faculty Articles

Cordyceps sinensis is a medicinal mushroom used for centuries in Asian countries as a health supplement and tonic. Hirsutella sinensis—the anamorphic, mycelial form of C. sinensis—possesses similar properties, and is increasingly used as a health supplement. Recently, C. sinensis extracts were shown to inhibit the production of the pro-inflammatory cytokine IL-1β in lipopolysaccharide-treated macrophages. However, the molecular mechanism underlying this process has remained unclear. In addition, whether H. sinensis mycelium (HSM) extracts also inhibit the production of IL-1β has not been investigated. In the present study, the HSM extract suppresses IL-1β and IL-18 secretion, and ATP-induced activation of caspase-1. Notably, …

Trident - March 2013, Dugoni School Of Dentistry

Trident

The newsletter of the Pacific Orthodontic Alumni Chapter at University of the Pacific, Arthur A. Dugoni School of Dentistry.

Ccl3 And Cxcl12 Production In Vitro By Dental Pulp Fibroblasts From Permanent And Deciduous Teeth Stimulated By Porphyromonas Gingivalis Lps, Carla Renata Sipert, Ana Carolina Morandini, Karin Cristina Da Silva Modena, Thiago José Dionísio, Maria Aparecida Andrade Moreira Machado, Sandra Helena Penha Oliveira, Ana Paula Campanelli, Carlos Ferreira Santos

All Dugoni School of Dentistry Faculty Articles

OBJECTIVE: The aim of this study was to compare the production of the chemokines CCL3 and CXCL12 by cultured dental pulp fibroblasts from permanent (PDPF) and deciduous (DDPF) teeth under stimulation by Porphyromonas gingivalis LPS (PgLPS).

MATERIAL AND METHODS: Primary culture of fibroblasts from permanent (n=3) and deciduous (n=2) teeth were established using an explant technique. After the fourth passage, fibroblasts were stimulated by increasing concentrations of PgLPS (0-10 µg/mL) at 1, 6 and 24 h. The cells were tested for viability through MTT assay, and production of the chemokines CCL3 and CXCL12 was determined through ELISA. Comparisons among samples …

Medicare Part D Roulette: Potential Implications Of Random Assignment And Plan Restrictions, Rajul A. Patel, Mark P. Walberg, Joseph A. Woelfel, Michelle M. Amaral, Paresh Varu

School of Pharmacy Faculty Articles

Background: Dual-eligible (Medicare/Medicaid) beneficiaries are randomly assigned to a benchmark plan, which provides prescription drug coverage under the Part D benefit without consideration of their prescription drug profile. To date, the potential for beneficiary assignment to a plan with poor formulary coverage has been minimally studied and the resultant financial impact to beneficiaries unknown.

Objective: We sought to determine cost variability and drug use restrictions under each available 2010 California benchmark plan.

Methods: Dual-eligible beneficiaries were provided Part D plan assistance during the 2010 annual election period. The Medicare Web site was used to determine benchmark plan costs and prescription …

Program Assessment: Enough Or Too Much?, Eric G. Boyce

School of Pharmacy Faculty Articles

No abstract provided.

Turning Stealth Liposomes Into Cationic Liposomes For Anticancer Drug Delivery, Vijay Gyanani

University of the Pacific Theses and Dissertations

Targeting the anticancer agents selectively to cancer cells is desirable to improve the efficacy and to reduce the side effects of anticancer therapy. Previously reported passive tumor targeting by PEGylated liposomes (stealth liposomes) have resulted in their higher tumor accumulation. However their interaction with cancer cells has been minimal due to the steric hindrance of the PEG coating. This dissertation reports two approaches to enhance the interaction of stealth liposomes with cancer cells. First, we designed a lipid-hydrazone-PEG conjugate that removes the PEG coating at acidic pH as in the tumor interstitium. However, such a conjugate was highly unstable on …