Medical Specialties Commons^™

St-Segment Elevation Myocardial Infarction In Patient With Left Ventricular Assist Device, Navin Rajagopalan, Ryan E. Wilson

The VAD Journal

Acute myocardial infarction is a rare event in a patient with a left ventricular assist device (LVAD). We present a case of ST-segment elevation myocardial infarction in a LVAD patient.

Procollagen C-Endopeptidase Enhancer Protein 2 (Pcpe2) Reduces Atherosclerosis In Mice By Enhancing Scavenger Receptor Class B1 (Sr-Bi)-Mediated High-Density Lipoprotein (Hdl)-Cholesteryl Ester Uptake, Ricquita D. Pollard, Christopher N. Blesso, Manal Zabalawi, Brian Fulp, Mark Gerelus, Xuewei Zhu, Erica W. Lyons, Nebil Nuradin, Omar L. Francone, Xiang-An Li, Daisy Sahoo, Michael J. Thomas, Mary G. Sorci-Thomas

Pediatrics Faculty Publications

Studies in human populations have shown a significant correlation between procollagen C-endopeptidase enhancer protein 2 (PCPE2) single nucleotide polymorphisms and plasma HDL cholesterol concentrations. PCPE2, a 52-kDa glycoprotein located in the extracellular matrix, enhances the cleavage of C-terminal procollagen by bone morphogenetic protein 1 (BMP1). Our studies here focused on investigating the basis for the elevated concentration of enlarged plasma HDL in PCPE2-deficient mice to determine whether they protected against diet-induced atherosclerosis. PCPE2-deficient mice were crossed with LDL receptor-deficient mice to obtain LDLr^-/-, PCPE2^-/- mice, which had elevated HDL levels compared with LDLr^-/- mice with similar …

Telemetric Blood Pressure Assessment In Angiotensin Ii-Infused Apoe-/- Mice: 28 Day Natural History And Comparison To Tail-Cuff Measurements, Christopher M. Haggerty, Andrea C. Mattingly, Ming C. Gong, Wen Su, Alan Daugherty, Brandon K. Fornwalt

Saha Cardiovascular Research Center Faculty Publications

Abdominal aortic aneurysm (AAA) is a disease of the aortic wall, which can progress to catastrophic rupture. Assessment of mechanical characteristics of AAA, such as aortic distensibility, may provide important insights to help identify at-risk patients and understand disease progression. While the majority of studies on this topic have focused on retrospective patient data, recent studies have used mouse models of AAA to prospectively evaluate the evolution of aortic mechanics. Quantification of aortic distensibility requires accurate measurement of arterial blood pressure, particularly pulse pressure, which is challenging to perform accurately in murine models. We hypothesized that volume/pressure tail-cuff measurements of …

Apoε2 And Education In Cognitively Normal Older Subjects With High Levels Of Ad Pathology At Autopsy: Findings From The Nun Study, Diego Iacono, Peter Zandi, Myron Gross, William R. Markesbery, Olga Pletnikova, Gay Rudow, Juan C. Troncoso

Sanders-Brown Center on Aging Faculty Publications

Asymptomatic Alzheimer's disease (ASYMAD) subjects are individuals characterized by preserved cognition before death despite substantial AD pathology at autopsy. ASYMAD subjects show comparable levels of AD pathology, i.e. β-amyloid neuritic plaques (Aβ-NP) and tau-neurofibrillary tangles (NFT), to those observed in mild cognitive impairment (MCI) and some definite AD cases. Previous clinicopathologic studies on ASYMAD subjects have shown specific phenomena of hypertrophy in the cell bodies, nuclei, and nucleoli of hippocampal pyramidal neurons and other cerebral areas. Since it is well established that the allele APOε4 is a major genetic risk factor for AD, we examined whether specific alleles of APOE …

Akt Inhibition Overcomes Rapamycin Resistance By Enhancing The Repressive Function Of Pras40 On Mtorc1/4e-Bp1 Axis, Wenting Mi, Qing Ye, Side Liu, Qing-Bai She

Markey Cancer Center Faculty Publications

The mTORC1 inhibitors, rapamycin and its analogs, are known to show only modest antitumor activity in clinic, but the underlying mechanisms remain largely elusive. Here, we found that activated AKT signaling is associated with rapamycin resistance in breast and colon cancers by sustained phosphorylation of the translational repressor 4E-BP1. Treatment of tumor cells with rapamycin or the AKT inhibitor MK2206 showed a limited activity in inhibiting 4E-BP1 phosphorylation, cap-dependent translation, cell growth and motility. However, treatment with both drugs resulted in profound effects in vitro and in vivo. Mechanistic investigation demonstrated that the combination treatment was required to effectively …

Calcium Channel Blockers, Progression To Dementia, And Effects On Amyloid Beta Peptide Production, Mark A. Lovell, Erin Abner, Richard Kryscio, Liou Xu, Shuling X. Fister, Bert C. Lynn

Sanders-Brown Center on Aging Faculty Publications

Previous epidemiologic studies suggest that antihypertensive drugs may be protective against cognitive decline. To determine if subjects enrolled in the University of Kentucky longitudinal aging study who used antihypertensive drugs showed diminished progression to dementia, we used a 3-parameter logistic regression model to compare the rate of progression to dementia for subjects who used any of the five common categories of antihypertensive drugs to those with similar demographic characteristics but who did not use antihypertensives. Regression modeling showed that subjects who used calcium channel blockers (CCBs) but not the other classes of antihypertensives showed a significant decrease in the rate …

Pannexin1 Channels Dominate Atp Release In The Cochlea Ensuring Endocochlear Potential And Auditory Receptor Potential Generation And Hearing, Jin Chen, Yan Zhu, Chun Liang, Jing Chen, Hong-Bo Zhao

Otolaryngology--Head & Neck Surgery Faculty Publications

Pannexin1 (Panx1) is a gap junction gene in vertebrates whose proteins mainly function as non-junctional channels on the cell surface. Panx1 channels can release ATP under physiological conditions and play critical roles in many physiological and pathological processes. Here, we report that Panx1 deficiency can reduce ATP release and endocochlear potential (EP) generation in the cochlea inducing hearing loss. Panx1 extensively expresses in the cochlea, including the cochlear lateral wall. We found that deletion of Panx1 in the cochlear lateral wall almost abolished ATP release under physiological conditions. Positive EP is a driving force for current through hair cells to …

An Ex Vivo Approach To Complex Renal Artery Aneurysm Repair, Noah T. Scherrer, Roberto Gedaly, Ramakrishna Venkatesh, Michael A. Winkler, Eleftherios S. Xenos

Surgery Faculty Publications

Ex vivo repair technique for a complex renal artery aneurysm may have several advantages. Smaller incision size and use of minimally invasive techniques may decrease incisional morbidity and improve recovery time, especially in patients with a high body mass index. Improved visualization afforded by back-table methods may also be valuable when repair of aneurysms involving multiple branches is necessary. We report of a successful case of laparoscopic nephrectomy, followed by back-table aneurysmorrhaphy and autotransplant, in a patient with a renal artery aneurysm.

Cellular And Deafness Mechanisms Underlying Connexin Mutation-Induced Hearing Loss - A Common Hereditary Deafness, Jeffrey C. Wingard, Hong-Bo Zhao

Otolaryngology--Head & Neck Surgery Faculty Publications

Hearing loss due to mutations in the connexin gene family, which encodes gap junctional proteins, is a common form of hereditary deafness. In particular, connexin 26 (Cx26, GJB2) mutations are responsible for ~50% of non-syndromic hearing loss, which is the highest incidence of genetic disease. In the clinic, Cx26 mutations cause various auditory phenotypes ranging from profound congenital deafness at birth to mild, progressive hearing loss in late childhood. Recent experiments demonstrate that congenital deafness mainly results from cochlear developmental disorders rather than hair cell degeneration and endocochlear potential reduction, while late-onset hearing loss results from reduction of active …

Successful Implementation Of A Packed Red Blood Cell And Fresh Frozen Plasma Transfusion Protocol In The Surgical Intensive Care Unit, Benjamin E. Szpila, Tezcan Ozrazgat-Baslanti, Jianyi Zhang, Jennifer Lanz, Ruth Davis, Annette Rebel, Erin Vanzant, Lori F. Gentile, Alex G. Cuenca, Darwin N. Ang, Huazhi Liu, Lawrence Lottenberg, Peggy Marker, Marc Zumberg, Azra Bihorac, Frederick A. Moore, Scott Brakenridge, Philip A. Efron

Anesthesiology Faculty Publications

BACKGROUND: Blood product transfusions are associated with increased morbidity and mortality. The purpose of this study was to determine if implementation of a restrictive protocol for packed red blood cell (PRBC) and fresh frozen plasma (FFP) transfusion safely reduces blood product utilization and costs in a surgical intensive care unit (SICU).

STUDY DESIGN: We performed a retrospective, historical control analysis comparing before (PRE) and after (POST) implementation of a restrictive PRBC/FFP transfusion protocol for SICU patients. Univariate analysis was utilized to compare patient demographics and blood product transfusion totals between the PRE and POST cohorts. Multivariate logistic regression …

Percutaneous Ultrasonic Debridement Of Tendinopathy—A Pilot Achilles Rabbit Model, Srinath Kamineni, Timothy Butterfield, Anthony Sinai

Orthopaedic Surgery and Sports Medicine Faculty Publications

BACKGROUND: Tendinopathy is a common clinical pathology, with mixed treatment results, especially when chronic. In this study, we examine the effects of an ultrasonic debridement modality in a rabbit tendinopathy model. We asked four questions: (1) Was it possible to create and visualize with ultrasound a tendinopathy lesion in a rabbit Achilles tendon? (2) Was it possible to guide a 19-gauge ultrasonic probe into the tendinopathy lesion? (3) Following ultrasonic treatment, was tendinopathy debris histologically present? and (4) Was the collagen profile qualitatively and quantitatively normalized following treatment?

METHODS: Skeletally mature female New Zealand white rabbits (n = 12) …

Ferritin Levels In The Cerebrospinal Fluid Predict Alzheimer's Disease Outcomes And Are Regulated By Apoe, Scott Ayton, Noel G. Faux, Ashley I. Bush, Charles D. Smith, Greg A. Jicha, Peter A. Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad, Alzheimer's Disease Neuroimaging Initiative

Neurology Faculty Publications

Brain iron elevation is implicated in Alzheimer's disease (AD) pathogenesis, but the impact of iron on disease outcomes has not been previously explored in a longitudinal study. Ferritin is the major iron storage protein of the body; by using cerebrospinal fluid (CSF) levels of ferritin as an index, we explored whether brain iron status impacts longitudinal outcomes in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. We show that baseline CSF ferritin levels were negatively associated with cognitive performance over 7 years in 91 cognitively normal, 144 mild cognitive impairment (MCI) and 67 AD subjects, and predicted MCI conversion to AD. …

Prospective Study Of Recovery From Copperhead Snake Envenomation: An Observational Study, Eric J. Lavonas, Charles J. Gerardo, Rebecca C. Bowers, Joann Short, Copperhead Snakebite Recovery Outcome Group

Emergency Medicine Faculty Publications

BACKGROUND: Although much is known about signs, symptoms, and management in the acute phase of crotaline snake envenomation, little is known about signs, symptoms, function, and quality of life during the recovery phase. The purpose of this observational pilot investigation is to evaluate the utility of several clinical outcome instruments in the setting of copperhead snakebite, and to characterize the clinical course of recovery.

METHODS: This is a multi-center prospective, open-label, observational study of patients envenomated by copperhead snakes. We administered the Disabilities of the Arm, Shoulder, and Hand (DASH), Lower Extremity Functional Scale (LEFS), Patient-Specific Functional Scale …

Triceps Activation Amplitudes During Functional Activities, Srinath Kamineni, Corey Gildea, Arthur J. Nitz, Timothy L. Uhl

Orthopaedic Surgery and Sports Medicine Faculty Publications

Objective: To investigate the muscular activation amplitudes of three regions of triceps musculature during functional activities. We hypothesized that the medial and lateral triceps would be greatest in the terminal 30° arc of extension activities.

Design: Cross sectional.

Setting: Musculoskeletal Clinical Laboratory.

Participants: 20 healthy subjects recruited from a sample of convenience.

Intervention: Fine wire electromyograhical (EMG) electrodes were placed into the medial, central, and lateral triceps to measure muscular activation amplitude and two dimensional electrogoniometric kinematic activity was recorded during functional activities associated with activities of daily living.

Main Outcome Measure(s): Root mean squared amplitudes of triceps muscles normalized …

Radon Potential, Geologic Formations, And Lung Cancer Risk, Ellen J. Hahn, Yevgeniya Gokun, William M. Andrews Jr., Bethany L. Overfield, Heather Robertson, Amanda T. Wiggins, Mary Kay Rayens

Nursing Faculty Publications

OBJECTIVE: Exposure to radon is associated with approximately 10% of U.S. lung cancer cases. Geologic rock units have varying concentrations of uranium, producing fluctuating amounts of radon. This exploratory study examined the spatial and statistical associations between radon values and geological formations to illustrate potential population-level lung cancer risk from radon exposure.

METHOD: This was a secondary data analysis of observed radon values collected in 1987 from homes (N = 309) in Kentucky and geologic rock formation data from the Kentucky Geological Survey. Radon value locations were plotted on digital geologic maps using ArcGIS and linked to specific geologic map …

Increasing Adipocyte Lipoprotein Lipase Improves Glucose Metabolism In High Fat Diet-Induced Obesity, R. Grace Walton, Beibei Zhu, Resat Unal, Michael Spencer, Manjula Sunkara, Andrew J. Morris, Richard Charnigo, Wendy S. Katz, Alan Daugherty, Deborah A. Howatt, Philip A. Kern, Brian S. Finlin

Barnstable Brown Diabetes Center Faculty Publications

Lipid accumulation in liver and skeletal muscle contributes to co-morbidities associated with diabetes and obesity. We made a transgenic mouse in which the adiponectin (Adipoq) promoter drives expression of lipoprotein lipase (LPL) in adipocytes to potentially increase adipose tissue lipid storage. These mice (Adipoq-LPL) have improved glucose and insulin tolerance as well as increased energy expenditure when challenged with a high fat diet (HFD). To identify the mechanism(s) involved, we determined whether the Adipoq-LPL mice diverted dietary lipid to adipose tissue to reduce peripheral lipotoxicity, but we found no evidence for this. Instead, characterization …

Powerful Anti-Tumor And Anti-Angiogenic Activity Of A New Anti-Vascular Endothelial Growth Factor Receptor 1 Peptide In Colorectal Cancer Models, Valeria Cicatiello, Ivana Apicella, Laura Tudisco, Valeria Tarallo, Luigi Formisano, Annamaria Sandomenico, Younghee Kim, Ana Bastos-Carvalho, Augusto Orlandi, Jayakrishna Ambati, Menotti Ruvo, Roberto Bianco, Sandro De Falco

Ophthalmology and Visual Science Faculty Publications

To assess the therapeutic outcome of selective block of VEGFR1, we have evaluated the activity of a new specific antagonist of VEGFR1, named iVR1 (inhibitor of VEGFR1), in syngenic and xenograft colorectal cancer models, in an artificial model of metastatization, and in laser-induced choroid neovascularization. iVR1 inhibited tumor growth and neoangiogenesis in both models of colorectal cancer, with an extent similar to that of bevacizumab, a monoclonal antibody anti-VEGF-A. It potently inhibited VEGFR1 phosphorylation in vivo, determining a strong inhibition of the recruitment of monocyte-macrophages and of mural cells as confirmed, in vitro, by the ability to inhibit …

Plasma Tnf-Α And Soluble Tnf Receptor Levels After Doxorubicin With Or Without Co-Administration Of Mesna-A Randomized, Cross-Over Clinical Study, John Hayslip, Emily Van Meter Dressler, Heidi L. Weiss, Tammy J. Taylor, Mara D. Chambers, Teresa Noel, Sumitra Miriyala, Jeriel T. R. Keeney, Xiaojia Ren, Rukhsana Sultana, Mary Vore, D. Allan Butterfield, Daret St. Clair, Jeffrey A. Moscow

Markey Cancer Center Faculty Publications

PURPOSE: Chemotherapy-induced cognitive impairment (CICI) is a common sequelae of cancer therapy. Recent preclinical observations have suggested that CICI can be mediated by chemotherapy-induced plasma protein oxidation, which triggers TNF-α mediated CNS damage. This study evaluated sodium-2-mercaptoethane sulfonate (Mesna) co-administration with doxorubicin to reduce doxorubicin-induced plasma protein oxidation and resultant cascade of TNF-α, soluble TNF receptor levels and related cytokines.

METHODS: Thirty-two evaluable patients were randomized using a crossover design to receive mesna or saline in either the first or second cycle of doxorubicin in the context of a standard chemotherapy regimen for either non-Hodgkin lymphoma or breast …

Closed Head Injury In An Age-Related Alzheimer Mouse Model Leads To An Altered Neuroinflammatory Response And Persistent Cognitive Impairment, Scott J. Webster, Linda J. Van Eldik, D. Martin Watterson, Adam D. Bachstetter

Sanders-Brown Center on Aging Faculty Publications

Epidemiological studies have associated increased risk of Alzheimer's disease (AD)-related clinical symptoms with a medical history of head injury. Currently, little is known about pathophysiology mechanisms linked to this association. Persistent neuroinflammation is one outcome observed in patients after a single head injury. Neuroinflammation is also present early in relevant brain regions during AD pathology progression. In addition, previous mechanistic studies in animal models link neuroinflammation as a contributor to neuropathology and cognitive impairment in traumatic brain injury (TBI) or AD-related models. Therefore, we explored the potential interplay of neuroinflammatory responses in TBI and AD by analysis of the temporal …

When Operating On Dead People Saves Lives: Benefits Of Surgical Organ Donor Intensivists, Kristin Long, Cynthia Talley, Rebecca B. Yarrison, Andrew Bernard

Surgery Faculty Publications

Solid organ transplantation has emerged as a life-saving treatment for many patients suffering from end-stage organ failure. Organs have been successfully recovered after a variety of aggressive interventions. We propose that decompressive laparotomy, when clinically indicated, should be considered in the aggressive resuscitation of potential organ donors. A thorough literature review examining aggressive interventions on potential organ donors was conducted after experience with a unique case at this institution. Articles were reviewed for the types of interventions performed as well as the time frame in relation to organ donation. In our case, several ethical issues were raised when considering decompressive …

What Did We Learn About Vads In 2014?, Maya Guglin

The VAD Journal

No abstract provided.

Targeting Human Central Nervous System Protein Kinases: An Isoform Selective P38Αmapk Inhibitor That Attenuates Disease Progression In Alzheimer's Disease Mouse Models, Saktimayee M. Roy, Valerie L. Grum-Tokars, James P. Schavocky, Faisal Saeed, Agnieszka Staniszewski, Andrew F. Teich, Ottavio Arancio, Adam D. Bachstetter, Scott J. Webster, Linda J. Van Eldik, George Minasov, Wayne F. Anderson, Jeffrey C. Pelletier, D. Martin Watterson

Spinal Cord and Brain Injury Research Center Faculty Publications

The first kinase inhibitor drug approval in 2001 initiated a remarkable decade of tyrosine kinase inhibitor drugs for oncology indications, but a void exists for serine/threonine protein kinase inhibitor drugs and central nervous system indications. Stress kinases are of special interest in neurological and neuropsychiatric disorders due to their involvement in synaptic dysfunction and complex disease susceptibility. Clinical and preclinical evidence implicates the stress related kinase p38αMAPK as a potential neurotherapeutic target, but isoform selective p38αMAPK inhibitor candidates are lacking and the mixed kinase inhibitor drugs that are promising in peripheral tissue disease indications have limitations for neurologic indications. Therefore, …

Chaperone Hsp47 Drives Malignant Growth And Invasion By Modulating An Ecm Gene Network, Jieqing Zhu, Gaofeng Xiong, Hanjiang Fu, B. Mark Evers, Binhua P. Zhou, Ren Xu

Markey Cancer Center Faculty Publications

The extracellular matrix (ECM) is a determining factor in the tumor microenvironment that restrains or promotes malignant growth. In this report, we show how the molecular chaperone protein Hsp47 functions as a nodal hub in regulating an ECM gene transcription network. A transcription network analysis showed that Hsp47 expression was activated during breast cancer development and progression. Hsp47 silencing reprogrammed human breast cancer cells to form growth-arrested and/or noninvasive structures in 3D cultures, and to limit tumor growth in xenograft assays by reducing deposition of collagen and fibronectin. Coexpression network analysis also showed that levels of microRNA(miR)-29b and -29c were …

Attenuation Of Traumatic Brain Injury-Induced Cognitive Impairment In Mice By Targeting Increased Cytokine Levels With A Small Molecule Experimental Therapeutic, Adam D. Bachstetter, Scott J. Webster, Danielle S. Goulding, Jonathan E. Morton, D. Martin Watterson, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Evidence from clinical studies and preclinical animal models suggests that proinflammatory cytokine overproduction is a potential driving force for pathology progression in traumatic brain injury (TBI). This raises the possibility that selective targeting of the overactive cytokine response, a component of the neuroinflammation that contributes to neuronal dysfunction, may be a useful therapeutic approach. MW151 is a CNS-penetrant, small molecule experimental therapeutic that selectively restores injury- or disease-induced overproduction of proinflammatory cytokines towards homeostasis. We previously reported that MW151 administered post-injury (p.i.) is efficacious in a closed head injury (CHI) model of diffuse TBI in mice. Here we test …

Lipid-Induced Epigenomic Changes In Human Macrophages Identify A Coronary Artery Disease-Associated Variant That Regulates Ppap2b Expression Through Altered C/Ebp-Beta Binding, Michael E. Reschen, Kyle J. Gaulton, Da Lin, Elizabeth J. Soilleux, Andrew J. Morris, Susan S. Smyth, Christopher A. O'Callaghan

Gill Heart & Vascular Institute Faculty Publications

Genome-wide association studies (GWAS) have identified over 40 loci that affect risk of coronary artery disease (CAD) and the causal mechanisms at the majority of loci are unknown. Recent studies have suggested that many causal GWAS variants influence disease through altered transcriptional regulation in disease-relevant cell types. We explored changes in transcriptional regulation during a key pathophysiological event in CAD, the environmental lipid-induced transformation of macrophages to lipid-laden foam cells. We used a combination of open chromatin mapping with formaldehyde-assisted isolation of regulatory elements (FAIRE-seq) and enhancer and transcription factor mapping using chromatin immuno-precipitation (ChIP-seq) in primary human macrophages before …

Detection Of Phlpp1Α/Β In Human And Mouse Brain By Different Anti-Phlpp1 Antibodies, Travis C. Jackson, Hülya Bayir, Milos D. Ikonomovic, Keri Janesko-Feldman, Zaichuan Mi, Tianyan Gao, Edwin K. Jackson, Patrick M. Kochanek

Markey Cancer Center Faculty Publications

Pleckstrin homology domain and leucine rich repeat protein phosphatase 1 (PHLPP1) is a member of the serine/threonine family of phosphatases. It has been studied in organs including brain, heart, pancreas, adipose, breast, and prostate. Human PHLPP1 encodes two splice variants - PHLPP1α (~140-150 kDa) and PHLPP1β (~180-190 kDa). Commercial antibodies are widely used to characterize PHLPP1 proteins in cells/tissues. Here we validate five different antibodies to detect PHLPP1α/β by Western blot using PHLPP1 WT/KO mice. All antibodies recognize PHLPP1β in brain. Only a single antibody (Cosmo Bio Co) detects PHLPP1α (~145-150 kDa). The other four antibodies detect a non-specific signal …

G9a Is Essential For Emt-Mediated Metastasis And Maintenance Of Cancer Stem Cell-Like Characters In Head And Neck Squamous Cell Carcinoma, Shuli Liu, Dongxia Ye, Wenzheng Guo, Wenwen Yu, Yue He, Jingzhou Hu, Yanan Wang, Ling Zhang, Yueling Liao, Hongyong Song, Shuangshuang Zhong, Dongliang Xu, Huijing Yin, Beibei Sun, Xiaofei Wang, Jingyi Liu, Yadi Wu, Binhua P. Zhou, Zhiyuan Zhang, Jiong Deng

Markey Cancer Center Faculty Publications

Head and neck squamous cell carcinoma (HNSCC) is a particularly aggressive cancer with poor prognosis, largely due to lymph node metastasis and local recurrence. Emerging evidence suggests that epithelial-to-mesenchymal transition (EMT) is important for cancer metastasis, and correlated with increased cancer stem cells (CSCs) characteristics. However, the mechanisms underlying metastasis to lymph nodes in HNSCC is poorly defined. In this study, we show that E-cadherin repression correlates with cancer metastasis and poor prognosis in HNSCC. We found that G9a, a histone methyltransferase, interacts with Snail and mediates Snail-induced transcriptional repression of E-cadherin and EMT, through methylation of histone H3 lysine-9 …

Ppm1a Regulates Antiviral Signaling By Antagonizing Tbk1-Mediated Sting Phosphorylation And Aggregation, Zexing Li, Ge Liu, Liwei Sun, Yan Teng, Xuejiang Guo, Jianhang Jia, Jiahao Sha, Xiao Yang, Dahua Chen, Qinmiao Sun

Markey Cancer Center Faculty Publications

Stimulator of interferon genes (STING, also known as MITA and ERIS) is critical in protecting the host against DNA pathogen invasion. However, the molecular mechanism underlying the regulation of STING remains unclear. Here, we show that PPM1A negatively regulates antiviral signaling by targeting STING in its phosphatase activity-dependent manner, and in a line with this, PPM1A catalytically dephosphorylates STING and TBK1 in vitro. Importantly, we provide evidence that whereas TBK1 promotes STING aggregation in a phosphorylation-dependent manner, PPM1A antagonizes STING aggregation by dephosphorylating both STING and TBK1, emphasizing that phosphorylation is crucial for the efficient activation of STING. Our …

Cystic Multiglandular Maternal Hyperparathyroidism Diagnosed By Neonatal Hypocalcemic Seizures, Kristin Long, Tessa Cartwright, David A. Sloan, Cortney Y. Lee

Surgery Faculty Publications

A 7-day-old male infant born to a healthy 33-year-old female at 37 weeks of gestation was brought to the local emergency department (ED) with sudden-onset tonic-clonic seizures. Laboratory testing revealed extreme hypocalcemia (ionized calcium of 3.2 mg/dl) and undetectable parathyroid hormone (PTH/ml). Concomitant evaluation of the mother revealed both elevated ionized calcium (5.9 mg/dl) and PTH (116 pg/ml). The mother underwent preoperative ultrasound localization and sestamibi scan, followed promptly by parathyroidectomy. Given the cystic appearance and presence of multiglandular disease, evaluation for familial cystic parathyroid adenomatosis (hyperparathyroidism-jaw bone-tumor syndrome) and MEN 1 were undertaken. The infant was stabilized and discharged …

Surgical Considerations Of Lvad Implantation In Patients With Prosthetic Valves, Igor D. Gregoric

The VAD Journal

No abstract provided.