Medicine and Health Sciences Commons^™

Pharmacotherapy For Uveitis: Current Management And Emerging Therapy., Robert J. Barry, Quan Dong Nguyen, Richard W. Lee, Philip I. Murray, Alastair K. Denniston

Journal Articles: Ophthalmology

Uveitis, a group of conditions characterized by intraocular inflammation, is a major cause of sight loss in the working population. Most uveitis seen in Western countries is noninfectious and appears to be autoimmune or autoinflammatory in nature, requiring treatment with immunosuppressive and/or anti-inflammatory drugs. In this educational review, we outline the ideal characteristics of drugs for uveitis and review the data to support the use of current and emerging therapies in this context. It is crucial that we continue to develop new therapies for use in uveitis that aim to suppress disease activity, prevent accumulation of damage, and preserve visual …

Transformation Of Human Cathelicidin Ll-37 Into Selective, Stable, And Potent Antimicrobial Compounds., Guangshun Wang, Mark L. Hanke, Biswajit Mishra, Tamara Lushnikova, Cortney E. Heim, Vinai Chittezham Thomas, Kenneth W. Bayles, Tammy Kielian

Journal Articles: Pathology and Microbiology

This Letter reports a family of novel antimicrobial compounds obtained by combining peptide library screening with structure-based design. Library screening led to the identification of a human LL-37 peptide resistant to chymotrypsin. This d-amino-acid-containing peptide template was active against Escherichia coli but not methicillin-resistant Staphylococcus aureus (MRSA). It possesses a unique nonclassic amphipathic structure with hydrophobic defects. By repairing the hydrophobic defects, the peptide (17BIPHE2) gained activity against the ESKAPE pathogens, including Enterococcus faecium, S. aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter species. In vitro, 17BIPHE2 could disrupt bacterial membranes and bind to DNA. In vivo, the peptide …

Unbiased Analysis Of Pancreatic Cancer Radiation Resistance Reveals Cholesterol Biosynthesis As A Novel Target For Radiosensitisation., Joshua J. Souchek, Michael J. Baine, Chi Lin, Satyanarayana Rachagani, Suprit Gupta, Sukhwinder Kaur, K Lester, D Zheng, S Chen, Lynette Smith, A Lazenby, Sonny L. Johansson, Maneesh Jain, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: Despite its promise as a highly useful therapy for pancreatic cancer (PC), the addition of external beam radiation therapy to PC treatment has shown varying success in clinical trials. Understanding PC radioresistance and discovery of methods to sensitise PC to radiation will increase patient survival and improve quality of life. In this study, we identified PC radioresistance-associated pathways using global, unbiased techniques.

METHODS: Radioresistant cells were generated by sequential irradiation and recovery, and global genome cDNA microarray analysis was performed to identify differentially expressed genes in radiosensitive and radioresistant cells. Ingenuity pathway analysis was performed to discover cellular pathways …

Clinical Use Of Rivaroxaban: Pharmacokinetic And Pharmacodynamic Rationale For Dosing Regimens In Different Indications., Toby Trujillo, Paul P. Dobesh

Journal Articles: Pharmacy Practice

Target-specific oral anticoagulants have become increasingly available as alternatives to traditional agents for the management of a number of thromboembolic disorders. To date, the direct Factor Xa inhibitor rivaroxaban is the most widely approved of the new agents. The dosing of rivaroxaban varies and adheres to specific schedules in each of the clinical settings in which it has been investigated. These regimens were devised based on the results of phase II dose-finding studies and/or pharmacokinetic modeling, and were demonstrated to be successful in randomized, phase III studies. In most cases, the pharmacodynamic profile of rivaroxaban permits once-daily dosing. A once-daily …

Hemichannels In Neurodegenerative Diseases: Is There A Link To Pathology?, Megan Bosch, Tammy Kielian

Journal Articles: Pathology and Microbiology

Although originally considered a structural component of gap junctions, connexin hemichannels (HCs) are now recognized as functional entities capable of influencing metabolic gradients within the CNS, allowing direct communication between the intra- and extracellular milieus. Besides connexins, HCs can also be formed by pannexins, which are not capable of gap junction assembly. Both positive and negative effects have been attributed to HC activity in the context of neurodegenerative diseases. For example, HCs can exert neuroprotective effects by promoting the uptake of neurotoxic molecules, whereas chronic HC opening can disrupt molecular gradients leading to cellular dysfunction and death. The latter scenario …

Quantification Of Left Atrial Strain And Strain Rate Using Cardiovascular Magnetic Resonance Myocardial Feature Tracking: A Feasibility Study., Johannes Tammo Kowallick, Shelby Kutty, Frank Edelmann, Amedeo Chiribiri, Adriana Villa, Michael Steinmetz, Jan Martin Sohns, Wieland Staab, Nuno Bettencourt, Christina Unterberg-Buchwald, Gerd Hasenfuß, Joachim Lotz, Andreas Schuster

Journal Articles: Cardiology

BACKGROUND: Cardiovascular Magnetic Resonance myocardial feature tracking (CMR-FT) is a quantitative technique tracking tissue voxel motion on standard steady-state free precession (SSFP) cine images to assess ventricular myocardial deformation. The importance of left atrial (LA) deformation assessment is increasingly recognized and can be assessed with echocardiographic speckle tracking. However atrial deformation quantification has never previously been demonstrated with CMR. We sought to determine the feasibility and reproducibility of CMR-FT for quantitative derivation of LA strain and strain rate (SR) myocardial mechanics.

METHODS: 10 healthy volunteers, 10 patients with hypertrophic cardiomyopathy (HCM) and 10 patients with heart failure and preserved ejection …

Clinical And Biochemical Function Of Polymorphic Nr0b1 Ggaa-Microsatellites In Ewing Sarcoma: A Report From The Children's Oncology Group., Michael J. Monument, Kirsten M. Johnson, Elizabeth Mcilvaine, Lisa Abegglen, W. Scott Watkins, Lynn B. Jorde, Richard B. Womer, Natalie Beeler, Laura Monovich, Elizabeth R. Lawlor, Julia A. Bridge, Joshua D. Schiffman, Mark D Krailo, R. Lor Randall, Stephen L. Lessnick

Journal Articles: Pathology and Microbiology

BACKGROUND: The genetics involved in Ewing sarcoma susceptibility and prognosis are poorly understood. EWS/FLI and related EWS/ETS chimeras upregulate numerous gene targets via promoter-based GGAA-microsatellite response elements. These microsatellites are highly polymorphic in humans, and preliminary evidence suggests EWS/FLI-mediated gene expression is highly dependent on the number of GGAA motifs within the microsatellite.

OBJECTIVES: Here we sought to examine the polymorphic spectrum of a GGAA-microsatellite within the NR0B1 promoter (a critical EWS/FLI target) in primary Ewing sarcoma tumors, and characterize how this polymorphism influences gene expression and clinical outcomes.

RESULTS: A complex, bimodal pattern of EWS/FLI-mediated gene expression was observed …

Variation Of Choroidal Thickness And Vessel Diameter In Patients With Posterior Non-Infectious Uveitis, Millena G. Bittencourt, Saleema Kherani, Daniel A. Ferraz, Mehreen Ansari, Humzah Nasir, Yasir J. Sepah, Mostafa S. Hanout, Diana V. Do, Quan Dong Nguyen

Journal Articles: Ophthalmology

Abstract

Background

Choroidal thickness (CTh) and choroidal vessel diameter (VD) in the Haler’s layer were evaluated as markers of inflammatory insult in non-infectious uveitis (NIU). Spectral-domain optical coherence tomography (Spectralis®, Heidelberg Engineering Inc.) scans were acquired from 23 normal subjects (39 eyes – group 1), 7 subjects with high myopia (14 eyes – group 2), and 19 patients with NIU (23 eyes – group 3). In groups 1 and 2, CTh and VD were measured at 3 different points of the same horizontal OCT scan passing through the fovea and a mean calculated. Mean CTh and VD were calculated in …

Novel Role Of Pancreatic Differentiation 2 In Facilitating Self-Renewal And Drug Resistance Of Pancreatic Cancer Stem Cells., Arokia P. Vaz, Moorthy P. Ponnusamy, Satyanarayana Rachagani, P Dey, Apar Kishor Ganti, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: Cancer stem cells (CSCs) contribute towards disease aggressiveness and drug resistance. Specific identification of CSC maintenance genes and targeting can improve the efficiency of currently available treatment modalities. Pancreatic differentiation 2 (PD2) has a major role in the self-renewal of mouse embryonic stem cells. In the present study, we investigated the role of PD2 in pancreatic CSCs.

METHODS: Characterisation of CSCs and non-CSCs from mouse models, pancreatic cancer cells and human tissues by CSC and self-renewal marker analysis using confocal assay. Effect of PD2 knockdown in CSCs (after gemcitabine treatment) was studied by immunoblot and apoptosis assays.

RESULTS: A …

A Concise Review On The Current Understanding Of Pancreatic Cancer Stem Cells., Arokia P. Vaz, Moorthy P. Ponnusamy, Parthasarathy Seshacharyulu, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

No abstract provided.

Division Of Rheumatology New Frontiers, Debra Bergman, John Keenan

New Frontiers

Table of Contents

• Nebraska Arthritis Outcomes Research Center puts UNMC on cutting edge
• Medical education: A fresh perspective
• The reader
• Lupus study becomes international affair
• The puzzle of ‘the loss of self-tolerance’
• An icon in rheumatology
• Registry, research offer insights into RA risk factors
• On the RISE
• RAIN man
• A top-tier team player
• Faculty Publications & Research Awards

Family-Specific, Novel, Deleterious Germline Variants Provide A Rich Resource To Identify Genetic Predispositions For Brcax Familial Breast Cancer., Hongxiu Wen, Yeong C. Kim, Carrie Snyder, Fengxia Xiao, Elizabeth A. Fleissner, Dina Becirovic, Jiangtao Luo, Bradley Downs, Simon Sherman, Kenneth Cowan, Henry T. Lynch, San Ming Wang

Journal Articles: Eppley Institute

BACKGROUND: Genetic predisposition is the primary risk factor for familial breast cancer. For the majority of familial breast cancer, however, the genetic predispositions remain unknown. All newly identified predispositions occur rarely in disease population, and the unknown genetic predispositions are estimated to reach up to total thousands. Family unit is the basic structure of genetics. Because it is an autosomal dominant disease, individuals with a history of familial breast cancer must carry the same genetic predisposition across generations. Therefore, focusing on the cases in lineages of familial breast cancer, rather than pooled cases in disease population, is expected to provide …

A Central Role For Carbon-Overflow Pathways In The Modulation Of Bacterial Cell Death., Vinai Chittezham Thomas, Marat Sadykov, Sujata S. Chaudhari, Joselyn Jones, Jennifer L. Endres, Todd J. Widhelm, Jong-Sam Ahn, Randeep S. Jawa, Matthew C. Zimmerman, Kenneth W. Bayles

Journal Articles: Pathology and Microbiology

Similar to developmental programs in eukaryotes, the death of a subpopulation of cells is thought to benefit bacterial biofilm development. However mechanisms that mediate a tight control over cell death are not clearly understood at the population level. Here we reveal that CidR dependent pyruvate oxidase (CidC) and α-acetolactate synthase/decarboxylase (AlsSD) overflow metabolic pathways, which are active during staphylococcal biofilm development, modulate cell death to achieve optimal biofilm biomass. Whereas acetate derived from CidC activity potentiates cell death in cells by a mechanism dependent on intracellular acidification and respiratory inhibition, AlsSD activity effectively counters CidC action by diverting carbon flux …

Heuristic Modeling Of Carcinogenesis For The Population With Dichotomous Susceptibility To Cancer: A Pancreatic Cancer Example., Tengiz Mdzinarishvili, Simon Sherman

Journal Articles: Eppley Institute

At present, carcinogenic models imply that all individuals in a population are susceptible to cancer. These models either ignore a fall of the cancer incidence rate at old ages, or use some poorly identifiable parameters for its accounting. In this work, a new heuristic model is proposed. The model assumes that, in a population, only a small fraction (pool) of individuals is susceptible to cancer and decomposes the problem of the carcinogenic modeling on two sequentially solvable problems: (i) determination of the age-specific hazard rate in individuals susceptible to cancer (individual hazard rate) from the observed hazard rate in the …

Interaction Of Apobec3a With Dna Assessed By Atomic Force Microscopy., Luda S. Shlyakhtenko, Alexander J. Lushnikov, Ming Li, Reuben S. Harris, Yuri L. Lyubchenko

Journal Articles: Pharmaceutical Sciences

The APOBEC3 family of DNA cytosine deaminases functions to block the spread of endogenous retroelements and retroviruses including HIV-1. Potency varies among family members depending on the type of parasitic substrate. APOBEC3A (A3A) is unique among the human enzymes in that it is expressed predominantly in myeloid lineage cell types, it is strongly induced by innate immune agonists such as type 1 interferon, and it has the capacity to accommodate both normal and 5-methyl cytosine nucleobases. Here we apply atomic force microscopy (AFM) to characterize the interaction between A3A and single- and double-stranded DNA using a hybrid DNA approach in …

Pd2/Paf1 Depletion In Pancreatic Acinar Cells Promotes Acinar-To-Ductal Metaplasia., Parama Dey, Satyanarayana Rachagani, Arokia P. Vaz, Moorthy P. Ponnusamy, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Pancreatic differentiation 2 (PD2), a PAF (RNA Polymerase II Associated Factor) complex subunit, is overexpressed in pancreatic cancer cells and has demonstrated potential oncogenic property. Here, we report that PD2/Paf1 expression was restricted to acinar cells in the normal murine pancreas, but its expression increased in the ductal cells of KrasG12D/Pdx1Cre (KC) mouse model of pancreatic cancer with increasing age, showing highest expression in neoplastic ductal cells of 50 weeks old mice. PD2/Paf1 was specifically expressed in amylase and CK19 double positive metaplastic ducts, representing intermediate structures during pancreatic acinar-to-ductal metaplasia (ADM). Similar PD2/Paf1 expression was observed in murine pancreas …

Omics Technologies And Neovascular Ocular Disorders., Daniel Petrovič, Quan Dong Nguyen, Borut Peterlin, Goran Petrovski

Journal Articles: Ophthalmology

No abstract provided.

Human Antimicrobial Peptides And Proteins, Guangshun Wang

Journal Articles: Pathology and Microbiology

As the key components of innate immunity, human host defense antimicrobial peptides and proteins (AMPs) play a critical role in warding off invading microbial pathogens. In addition, AMPs can possess other biological functions such as apoptosis, wound healing, and immune modulation. This article provides an overview on the identification, activity, 3D structure, and mechanism of action of human AMPs selected from the antimicrobial peptide database. Over 100 such peptides have been identified from a variety of tissues and epithelial surfaces, including skin, eyes, ears, mouths, gut, immune, nervous and urinary systems. These peptides vary from 10 to 150 amino acids …

University Students And The Risk Of Hiv And Other Sexually Transmitted Infections In Uganda: The Crane Survey., George W. Rutherford, Andrew Anglemyer, Danstan Bagenda, Michael Muyonga, Christina P. Lindan, Joseph L. Barker, Lisa Johnston, Wolfgang Hladik

Journal Articles: Epidemiology

Adolescents and young adults are at high risk of human immunodeficiency virus (HIV) infection in sub-Saharan Africa. Previous reports have found that university students in Africa comprise a sexually active population, although the prevalence of HIV or sexually transmitted infections (STI) has not been measured. We conducted a cross-sectional survey of students from five large universities in Kampala, Uganda, using respondent-driven sampling. We asked students to complete behavioral questionnaires and provide biological samples to test for HIV, Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum, Trichomonas vaginalis, and bacterial vaginosis. We enrolled 649 students and obtained interpretable data from 640. Around 50% …

Pathobiological Implications Of Mucin (Muc) Expression In The Outcome Of Small Bowel Cancer., Hiroaki Shibahara, Michiyo Higashi, Chihaya Koriyama, Seiya Yokoyama, Iwao Kitazono, Yasuhiro Kurumiya, Michihiko Narita, Shingo Kuze, Takanori Kyokane, Saburo Mita, Toshiyuki Arai, Takehito Kato, Norihiro Yuasa, Ryuzo Yamaguchi, Hitoshi Kubota, Hideaki Suzuki, Satoshi Baba, Karine Rousseau, Surinder K. Batra, Suguru Yonezawa

Journal Articles: Biochemistry & Molecular Biology

Mucins have been associated with survival in various cancer patients, but there have been no studies of mucins in small bowel carcinoma (SBC). In this study, we investigated the relationships between mucin expression and clinicopathologic factors in 60 SBC cases, in which expression profiles of MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC6 and MUC16 in cancer and normal tissues were examined by immunohistochemistry. MUC1, MUC5AC and MUC16 expression was increased in SBC lesions compared to the normal epithelium, and expression of these mucins was related to clinicopathologic factors, as follows: MUC1 [tumor location (p = 0.019), depth (p = 0.017) and …

Diagnosis Of Pancreatic Neoplasms Using A Novel Method Of Dna Methylation Analysis Of Mucin Expression In Pancreatic Juice., Seiya Yokoyama, Sho Kitamoto, Michiyo Higashi, Yuko Goto, Taro Hara, Dai Ikebe, Taketo Yamaguchi, Yoshifumi Arisaka, Toru Niihara, Hiroto Nishimata, Sadao Tanaka, Kyoichi Takaori, Surinder K. Batra, Suguru Yonezawa

Journal Articles: Biochemistry & Molecular Biology

Mucins (MUC) play crucial roles in carcinogenesis and tumor invasion in pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasms (IPMNs). Our immunohistochemistry (IHC) studies have shown a consensus position on mucin expression profiles in pancreatic neoplasms as follows: MUC1-positive but MUC2-negative expression in PDACs; MUC1-negative but MUC2-positive expression in intestinal-type IPMNs (dangerous type); MUC1-negative and MUC2-negative expression in gastric-type IPMNs (safe type); High MUC4 expression in PDAC patients with a poor outcome; and MUC4-positive expression in intestinal-type IPMNs. We also showed that three mucin genes (MUC1, MUC2 and MUC4) expression in cancer cell line was regulated by DNA methylation. …

Fundus Autofluorescence Imaging: Fundamentals And Clinical Relevance., Yasir J. Sepah, Abeer Akhtar, Mohammad Ali Sadiq, Yamama Hafeez, Humzah Nasir, Brian Perez, Narissa Mawji, Diana J. Dean, Daniel Ferraz, Quan Dong Nguyen

Journal Articles: Ophthalmology

Fundus autofluorescence (FAF), a relatively new imaging modality, focuses on the fluorescent properties of pigments in the retina to generate images that help us view various disease processes from a different perspective. It aids us in the understanding of the pathophysiology of different retinal disorders. Recently, FAF imaging is being used commonly to help us in the diagnosis, prognosis as well as in determining the treatment response of various retinal disorders. It generates an image based on the distribution pattern of a fluorescent pigment called lipofuscin. Knowing the distribution pattern of lipofuscin in the normal retina is key to understanding …

Efficacy And Safety Of Sitagliptin For The Treatment Of New-Onset Diabetes After Renal Transplantation., Brian P. Boerner, Clifford D. Miles, Vijay Shivaswamy

Journal Articles: Diabetes, Endocrinology & Metabolism

New-onset diabetes after transplantation (NODAT) is a common comorbidity after renal transplantation. Though metformin is the first-line agent for the treatment of type 2 diabetes, in renal transplant recipients, metformin is frequently avoided due to concerns about renal dysfunction and risk for lactic acidosis. Therefore, alternative first-line agents for the treatment of NODAT in renal transplant recipients are needed. Sitagliptin, a dipeptidyl-peptidase-4 (DPP-4) inhibitor, has a low incidence of hypoglycemia, is weight neutral, and, in a small study, did not affect immunosuppressant levels. However, long-term sitagliptin use for the treatment of NODAT in kidney transplant recipients has not been studied. …

Evidence For Aberrant Astrocyte Hemichannel Activity In Juvenile Neuronal Ceroid Lipofuscinosis (Jncl)., Maria Burkovetskaya, Nikolay Karpuk, Juan Xiong, Megan Bosch, Michael D. Boska, Hideyuki Takeuchi, Akio Suzumura, Tammy Kielian

Journal Articles: Pathology and Microbiology

Juvenile Neuronal Ceroid Lipofuscinosis (JNCL) is a lysosomal storage disease caused by an autosomal recessive mutation in CLN3 that leads to vision loss, progressive cognitive and motor decline, and premature death. Morphological evidence of astrocyte activation occurs early in the disease process and coincides with regions where neuronal loss eventually ensues. However, the consequences of CLN3 mutation on astrocyte function remain relatively ill-defined. Astrocytes play a critical role in CNS homeostasis, in part, by their ability to regulate the extracellular milieu via the formation of extensive syncytial networks coupled by gap junction (GJ) channels. In contrast, unopposed hemichannels (HCs) have …

The Cancer Care Workforce In Nebraska, Aastha Chandak, Fausto R. Loberiza Jr., Marlene Deras, James O. Armitage, Julie M. Vose, Jim P. Stimpson

Reports: Center for Health Policy

Although cancer is the leading cause of death in Nebraska, the adequacy of Nebraska’s cancer care workforce to care for the cancer population is unknown. Therefore, we used workforce survey data for 2008-2012 from the Health Professions Tracking Service to analyze the cancer care workforce supply in Nebraska. We found that from 2008 to 2012, the cancer care workforce for adults outpaced cancer prevalence. We outline several policy options to improve Nebraska’s cancer care workforce capacity, and we consider the effect the Affordable Care Act may have on Nebraska’s cancer care workforce

Altered Expression Of Transmembrane Mucins, Muc1 And Muc4, In Bladder Cancer: Pathological Implications In Diagnosis., Sukhwinder Kaur, Navneet Momi, Subhankar Chakraborty, David G. Wagner, Adam J. Horn, Subodh M. Lele, Dan Theodorescu, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

PURPOSE: Radical changes in both expression and glycosylation pattern of transmembrane mucins have been observed in various malignancies. We and others have shown that MUC1 and MUC4, two transmembrane mucins, play a sentinel role in cell signaling events that drive several epithelial malignancies. In the present study, we investigated the expression profile of MUC1 and MUC4 in the non-neoplastic bladder urothelium, in various malignant neoplasms of bladder and in bladder carcinoma cell lines.

MATERIAL AND METHODS: Immunohistochemistry was performed on tissue sections from the urinary bladder biopsies, resection samples and tissue microarrays (TMAs) with monoclonal antibodies specific for MUC1 and …

Patterns And Predictors Of Self-Medication In Northern Uganda., Moses Ocan, Freddie Bwanga, Godfrey S. Bbosa, Danstan Bagenda, Paul Waako, Jasper Ogwal-Okeng, Celestino Obua

Journal Articles: Epidemiology

Self-medication with antimicrobial agents is a common form of self-care among patients globally with the prevalence and nature differing from country to country. Here we assessed the prevalence and predictors of antimicrobial self-medication in post-conflict northern Uganda. A cross-sectional study was carried out using structured interviews on 892 adult (≥18 years) participants. Information on drug name, prescriber, source, cost, quantity of drug obtained, and drug use was collected. Households were randomly selected using multistage cluster sampling method. One respondent who reported having an illness within three months in each household was recruited. In each household, information was obtained from only …

Functional Proteomic Analysis Reveals The Involvement Of Kiaa1199 In Breast Cancer Growth, Motility And Invasiveness., Mohammad-Saeid Jami, Jinxuan Hou, Miao Liu, M L. Varney, Hesham Hassan, Jixin Dong, Liying Geng, J. Wang, Fang Yu, Xin Huang, Hong Peng, Kai Fu, Yan Li, Rakesh Singh, Shi-Jian Ding

Journal Articles: Pathology and Microbiology

BACKGROUND: KIAA1199 is a recently identified novel gene that is up-regulated in human cancer with poor survival. Our proteomic study on signaling polarity in chemotactic cells revealed KIAA1199 as a novel protein target that may be involved in cellular chemotaxis and motility. In the present study, we examined the functional significance of KIAA1199 expression in breast cancer growth, motility and invasiveness.

METHODS: We validated the previous microarray observation by tissue microarray immunohistochemistry using a TMA slide containing 12 breast tumor tissue cores and 12 corresponding normal tissues. We performed the shRNA-mediated knockdown of KIAA1199 in MDA-MB-231 and HS578T cells to …

Xiap Antagonist Embelin Inhibited Proliferation Of Cholangiocarcinoma Cells., Cody J. Wehrkamp, Ashley R. Gutwein, Sathish Kumar Natarajan, Mary Anne Phillippi, Justin L. Mott

Journal Articles: Biochemistry & Molecular Biology

Cholangiocarcinoma cells are dependent on antiapoptotic signaling for survival and resistance to death stimuli. Recent mechanistic studies have revealed that increased cellular expression of the E3 ubiquitin-protein ligase X-linked inhibitor of apoptosis (XIAP) impairs TRAIL- and chemotherapy-induced cytotoxicity, promoting survival of cholangiocarcinoma cells. This study was undertaken to determine if pharmacologic antagonism of XIAP protein was sufficient to sensitize cholangiocarcinoma cells to cell death. We employed malignant cholangiocarcinoma cell lines and used embelin to antagonize XIAP protein. Embelin treatment resulted in decreased XIAP protein levels by 8 hours of treatment with maximal effect at 16 hours in KMCH and Mz-ChA-1 …

Prevention Of Arteriovenous Shunt Occlusion Using Microbubble And Ultrasound Mediated Thromboprophylaxis., Shelby Kutty, Juefei Wu, James M. Hammel, Joseph R. Abraham, Jeeva Venkataraman, Ibrahim Abdullah, David A. Danford, Stanley J. Radio, John Lof, Thomas R. Porter

Journal Articles: Pediatrics

BACKGROUND: Palliative shunts in congenital heart disease patients are vulnerable to thrombotic occlusion. High mechanical index (MI) impulses from a modified diagnostic ultrasound (US) transducer during a systemic microbubble (MB) infusion have been used to dissolve intravascular thrombi without anticoagulation, and we sought to determine whether this technique could be used prophylactically to reduce thrombus burden and prevent occlusion of surgically placed extracardiac shunts.

METHODS AND RESULTS: Heparin-bonded ePTFE tubular vascular shunts of 4 mm×2.5 cm (Propaten; W.L Gore) were surgically placed in 18 pigs: a right-sided side-to-side arteriovenous (AV, carotid-jugular) shunt, and a left-sided arterio-arterial (AA, carotid-carotid) interposition shunt …