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Geriatric Hepatology: The Hepatic Diseases Of The Elderly And Liver Transplant, Shima Ghavimi, Hamed Azimi, Neel Patel, Oleg Shulik

Internal Medicine

Introduction: With the aging US population, chronic liver diseases are becoming more commonly diagnosed in the geriatric population. Advanced age leads to changes in liver blood flow, volume, morphology and normal physiology. This predisposes elderly patients to develop certain chronic liver diseases. Also, the clinical course and management differ in an older patient when compared to a younger patient. Some causes of chronic liver disease in the geriatric population include Hepatitis A, B, C, Non-Alcoholic Fatty liver disease, prolonged alcohol use and inflammation. Many chronic liver diseases are characterized by a slow, indolent course of progression with non-specific symptoms and …

Identification Of Monocyte-Like Precursors Of Granulocytes In Cancer As A Mechanism For Accumulation Of Pmn-Mdscs., Jérôme Mastio, Thomas Condamine, George Dominguez, Andrew V Kossenkov, Laxminarasimha Donthireddy, Filippo Veglia, Cindy Lin, Fang Wang, Shuyu Fu, Jie Zhou, Patrick Viatour, Sergio Lavilla-Alonso, Alexander T. Polo, Evgenii N. Tcyganov, Charles Mulligan, Brian Nam, Joseph Bennett, Gregory Masters, Michael Guarino, Amit Kumar, Yulia Nefedova, Robert H. Vonderheide, Lucia R. Languino, Scott I. Abrams, Dmitry I. Gabrilovich

Department of Cancer Biology Faculty Papers

We have identified a precursor that differentiates into granulocytes in vitro and in vivo yet belongs to the monocytic lineage. We have termed these cells monocyte-like precursors of granulocytes (MLPGs). Under steady state conditions, MLPGs were absent in the spleen and barely detectable in the bone marrow (BM). In contrast, these cells significantly expanded in tumor-bearing mice and differentiated to polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Selective depletion of monocytic cells had no effect on the number of granulocytes in naive mice but decreased the population of PMN-MDSCs in tumor-bearing mice by 50%. The expansion of MLPGs was found to be …

Surgical Stress And Cancer Progression: The Twisted Tango., Zhiwei Chen, Peidong Zhang, Ya Xu, Jiahui Yan, Zixuan Liu, Wayne Bond Lau, Bonnie Lau, Ying Li, Xia Zhao, Yuquan Wei, Shengtao Zhou

Department of Emergency Medicine Faculty Papers

Surgical resection is an important avenue for cancer treatment, which, in most cases, can effectively alleviate the patient symptoms. However, accumulating evidence has documented that surgical resection potentially enhances metastatic seeding of tumor cells. In this review, we revisit the literature on surgical stress, and outline the mechanisms by which surgical stress, including ischemia/reperfusion injury, activation of sympathetic nervous system, inflammation, systemically hypercoagulable state, immune suppression and effects of anesthetic agents, promotes tumor metastasis. We also propose preventive strategies or resolution of tumor metastasis caused by surgical stress.

Eosinophilic Dermatosis Of Hematologic Malignancy Responding To Dupilumab In A Patient With Chronic Lymphocytic Leukemia., Annie Jin, Bobak T. Pousti, Kevin T. Savage, Nicholas K. Mollanazar, Jason B. Lee, Sylvia Hsu

Department of Dermatology and Cutaneous Biology Faculty Papers

Leukemia cutis (LC) and eosinophilic dermatosis of hematologic malignancy (EDHM) are rare cutaneous manifestations of hematologic malignancies. Various therapeutic options have been reported, with largely underwhelming responses. We present a patient with chronic lymphocytic leukemia (CLL) with concomitant LC and EDHM who was treated with dupilumab.

Pioneers In Dermatology And Venereology: An Interview With Prof. Lawrence C. Parish., Lawrence Charles Parish

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

The Phosphatase Ubash3b/Sts-1 Is A Negative Regulator Of Bcr-Abl Kinase Activity And Leukemogenesis, Afsar Ali Mian, Ines Baumann, Marcus Liebermann, Florian Grebien, Giulio Superti-Furga, Martin Ruthardt, Oliver G. Ottmann, Oliver Hantschel

Centre for Regenerative Medicine & Stem Cell Research

No abstract provided.

Colostrum And Mature Breast Milk Analysis Of Serum Irisin And Sterol Regulatory Element-Binding Proteins-1c In Gestational Diabetes Mellitus, Syeda Sadia Fatima, Erum Khalid, Asma Akbar Ladak, Syed Adnan Ali

Department of Biological & Biomedical Sciences

Background: We aimed to evaluate irisin and SREBP-1c levels in serum, colostrum and mature breast milk in women with and without gestational diabetes (GDM); and to relate them with maternal glucose, lipid profile and weight status of babies.
Methods: GDM positive women (n = 33) and normal glucose tolerant women (NGT) (n = 33) were recruited. Maternal blood samples were collected at 28th week of gestation and later at 6-week post-partum while breast milk samples of the lactating mothers were collected within 72 hours of birth (colostrum) and at 6 weeks post-partum (mature milk). Irisin and SREBP-1c levels were analyzed …

Illegal Motorcycle Street Racing- A Growing Threat To Public Safety, Madiha Mumshad, Aisha Ashraf

Department of Emergency Medicine

No abstract provided.

Collaborative International Research In Clinical And Longitudinal Experience Study In Nmosd., Lawrence J Cook, John W Rose, Jessica S Alvey, Anna Marie Jolley, Renee Kuhn, Brie Marron, Melissa Pederson, Rene Enriquez, Jeff Yearley, Stephen Mckechnie, May H Han, Anna J Tomczak, Michael Levy, Maureen A Mealy, Jessica Coleman, Jeffrey L Bennett, Ruth Johnson, Myka Barnes-Garcia, Anthony L Traboulsee, Robert L Carruthers, Lisa Eunyoung Lee, Julia J Schubert, Katrina Mcmullen, Ilya Kister, Zoe Rimler, Allyson Reid, Nancy L Sicotte, Sarah M Planchon, Jeffrey A Cohen, Diane Ivancic, Jennifer L Sedlak, Ilana Katz Sand, Pavle Repovic, Lilyana Amezcua, Ana Pruitt, Erika Amundson, Tanuja Chitnis, Devin S Mullin, Eric C Klawiter, Andrew W Russo, Claire S Riley, Kaho B Onomichi, Libby Levine, Katherine E Nelson, Nancy M Nealon, Casey Engel, Mason Kruse-Hoyer, Melanie Marcille, Leticia Tornes, Anne Rumpf, Angela Greer, Megan Kenneally Behne, Renee R Rodriguez, Daniel W Behne, Derek W Blackway, Brian Coords, Terrence F Blaschke, Judy Sheard, Terry J Smith, Jacinta M Behne, Michael R Yeaman

Articles, Abstracts, and Reports

Objective: To develop a resource of systematically collected, longitudinal clinical data and biospecimens for assisting in the investigation into neuromyelitis optica spectrum disorder (NMOSD) epidemiology, pathogenesis, and treatment.

Methods: To illustrate its research-enabling purpose, epidemiologic patterns and disease phenotypes were assessed among enrolled subjects, including age at disease onset, annualized relapse rate (ARR), and time between the first and second attacks.

Results: As of December 2017, the Collaborative International Research in Clinical and Longitudinal Experience Study (CIRCLES) had enrolled more than 1,000 participants, of whom 77.5% of the NMOSD cases and 71.7% of the controls continue in active follow-up. Consanguineous …

Medical Evaluation And Management Of Male And Female Voiding Dysfunction: A Review., Alana Murphy, Seth Teplitsky, Akhil K. Das, Joon Yau Leong, Andrew Margules, Costas D. Lallas

Department of Urology Faculty Papers

A significant workforce shortage of urologists available to serve the US population has been projected to occur over the next decade. Accordingly, much of the management of urologic patients will need to be assumed by other specialties and practitioners. Since primary care physicians are often first evaluate common urologic complaints, it makes sense that these physicians are in an excellent position to intervene in the management of these patients when appropriate. One of the most common complaints in urology is voiding dysfunction. The incidence of voiding dysfunction increases with age, with conservative estimates showing that over 50% of elderly patients …

Etiology And Clinical Patterns Of Uveitis At Three Ophthalmic Clinics In Tajikistan, Sayyora Yuldasheva, Saidbeg Satorov, Shekhratdzon Satorov, Vyacheslav Dushenkov

Publications and Research

A prospective observational study was conducted at three ophthalmic clinics to assess the clinical patterns and etiology of uveitis in the Central Asia Republic of Tajikistan. All patients underwent physical and ophthalmologic examinations. Extensive efforts were made to determine the etiology of uveitis, including workups for Behçet's Disease (BD) and Vogt–Koyanagi–Harada (VKH) syndrome. All patients were tested for the presence of HLA-B27. Presence and/or history of tuberculosis and syphilis were ruled out. HSV, CMV, Chlamydia trachomatis and HIV antibody titers were determined by ELISA. Uveitis was diagnosed in 51 patient ages 14 to 60 were with women accounted for 60.8%. …

Patient And Provider Perspectives On Sexual History Taking During Gynecological Care: A Pilot Study In An Academic Family Medical Setting In New York City, Ashley M. Chastain

Dissertations and Theses

Background: In the United States (US), women face a number of serious issues concerning sexual health. Current surveillance data indicates that overall rates of bacterial sexually transmitted infections (STIs) are increasing rapidly. While rates of new diagnoses have decreased, the risks of acquiring HIV are still relatively high for some females, specifically Black/African-American women. In New York City (NYC), where this dissertation research was conducted, similar HIV/STI rates exist among females of reproductive age (aged 15-44). Among women in the US, there are also high estimated rates of other sexual health problems, such as sexual anxiety, sexual dysfunction, and intimate …

What, When And For Whom Model Of Nutrition: A Health Management Approach, Muhammad Rafiq

Pakistan Journal of Neurological Sciences (PJNS)

Studies have shown that nutrition plays an important role in the pathophysiology of different health issues either physiological, or psychological. Nutrition is implicated in the development of health issues in different ways. The purpose of this mini review was to suggest a comprehensive model of nutrition, “What, When and for Whom Model of Nutrition”, in the light of existing literature. For this purpose, existing literature was explored to study the role of nutrition on mental health in perspective to, what type of nutrition, when it is consumed and/or who consumes it. Researchers concluded that it is not only what we …

Detection And Concentration Of Plasma Aflatoxin Is Associated With Detection Of Oncogenic Human Papillomavirus In Kenyan Women, Jianjun Zhang, Elkanah Omenge, Philip Tonui, Yan Tong, Titus Manai, Stephen Kiptoo, Kapten Muthoka, John Groopman, Joshua Smith, Erin Madeen

Obstetrics and Gynaecology, East Africa

Background: Cervical cancer is common in Kenyan women. Cofactors in addition to infection with oncogenic human papillomavirus (HPV) are likely to be important in causing cervical cancer, because only a small percentage of HPV-infected women will develop this malignancy. Kenyan women are exposed to dietary aflatoxin, a potent carcinogen and immunosuppressive agent, which may be such a cofactor.

Methods: Demographics, behavioral data, plasma, and cervical swabs were collected from 88 human immunodeficiency virus-uninfected Kenyan women without cervical dysplasia. Human papillomavirus detection was compared between women with or without plasma aflatoxin B1-lysine (AFB1-lys) and evaluated in relation to AFB1-lys concentration.

Results: …

The Association Of Tas1r2 To Dental And Cardiovascular Health, Joseph Keryakos, Annika Van Oosbree, Alyssa Marie Kiesow

Faculty Work Comprehensive List

Despite brushing and/or flossing their teeth twice daily, many people are still susceptible to dental cavities and tooth decay. This research investigates the genetic and cardiovascular health behind this phenomenon. Two gene variants related to taste pathways, taste 1 receptor member 2 (TAS1R2) and taste 2 receptor member 38 (TAS2R38), were tested on the DNA of 20 students at Northern State University (10 males and 10 females). In concert with genetic screening, tooth impressions were taken of the participants’ upper and lower jaws along with salivary pH, heart rates, and blood pressures. Participants’ cavities and fillings were counted and their …

Association Of Fish Oil And Physical Activity On Mobility Disability In Older Adults, Anoop T. Balachandran

Publications and Research

Purpose: This study aimed to examine whether long-term fish oil (FO) supplementation is associated with a lower risk of mobility disability and enhances benefits of physical activity (PA). Methods: A total of 1635 sedentary adults age 70 to 89 yr from the Lifestyle Interventions and Independence for Elders single-blinded randomized,multicenter clinical trial, which compared a structured PA program to a health education program. Primary outcome was incident major mobility disability (MMD), defined by loss of ability to walk 400 m, measured every 6 months for an average of 2.6 yr. Secondary outcomes included persistent mobility disability, Short Physical Performance Battery, …

Nuclear Receptor Subfamily 4 Group A Member 2 Inhibits Activation Of Erk Signaling And Cell Growth In Response To Β-Adrenergic Stimulation In Adult Rat Cardiomyocytes, Sadia Ashraf, Yassmin K Hegazy, Romain Harmancey

Faculty, Staff and Student Publications

Sustained elevation of sympathetic activity is an important contributor to pathological cardiac hypertrophy, ventricular arrhythmias, and left ventricular contractile dysfunction in chronic heart failure. The orphan nuclear receptor NR4A2 is an immediate early-response gene activated in the heart under β-adrenergic stimulation. The goal of this study was to identify the transcriptional remodeling events induced by increased NR4A2 expression in cardiomyocytes and their impact on the physiological response of those cells to sustained β-adrenergic stimulation. Treatment of adult rat ventricular myocytes with isoproterenol induced a rapid (<4 >h) increase in NR4A2 levels that was accompanied by a transient (<24 >h) increase …

Vitamin D Status And Risk Of Incident Tuberculosis Disease: A Nested Case-Control Study, Systematic Review, And Individual-Participant Data Meta-Analysis, Omowunmi Aibana, Chuan-Chin Huang, Said Aboud, Alberto Arnedo-Pena, Mercedes C Becerra, Juan Bautista Bellido-Blasco, Ramesh Bhosale, Roger Calderon, Silvia Chiang, Carmen Contreras, Ganmaa Davaasambuu, Wafaie W Fawzi, Molly F Franke, Jerome T Galea, Daniel Garcia-Ferrer, Maria Gil-Fortuño, Barbará Gomila-Sard, Amita Gupta, Nikhil Gupte, Rabia Hussain, Jesus Iborra-Millet, Najeeha T Iqbal, Jose Vicente Juan-Cerdán, Aarti Kinikar, Leonid Lecca, Vidya Mave, Noemi Meseguer-Ferrer, Grace Montepiedra, Ferdinand M Mugusi, Olumuyiwa A Owolabi, Julie Parsonnet, Freddy Roach-Poblete, Maria Angeles Romeu-García, Stephen A Spector, Christopher R Sudfeld, Mark W Tenforde, Toyin O Togun, Rosa Yataco, Zibiao Zhang, Megan B Murray

Faculty, Staff and Student Publications

BACKGROUND: Few studies have evaluated the association between preexisting vitamin D deficiency and incident tuberculosis (TB). We assessed the impact of baseline vitamins D levels on TB disease risk.

METHODS AND FINDINGS: We assessed the association between baseline vitamin D and incident TB in a prospective cohort of 6,751 HIV-negative household contacts of TB patients enrolled between September 1, 2009, and August 29, 2012, in Lima, Peru. We screened for TB disease at 2, 6, and 12 months after enrollment. We defined cases as household contacts who developed TB disease at least 15 days after enrollment of the index patient. …

Nuclear Receptor Subfamily 4 Group A Member 2 Inhibits Activation Of Erk Signaling And Cell Growth In Response To Β-Adrenergic Stimulation In Adult Rat Cardiomyocytes, Sadia Ashraf, Yassmin K Hegazy, Romain Harmancey

Faculty, Staff and Student Publications

Sustained elevation of sympathetic activity is an important contributor to pathological cardiac hypertrophy, ventricular arrhythmias, and left ventricular contractile dysfunction in chronic heart failure. The orphan nuclear receptor NR4A2 is an immediate early-response gene activated in the heart under β-adrenergic stimulation. The goal of this study was to identify the transcriptional remodeling events induced by increased NR4A2 expression in cardiomyocytes and their impact on the physiological response of those cells to sustained β-adrenergic stimulation. Treatment of adult rat ventricular myocytes with isoproterenol induced a rapid (<4 >h) increase in NR4A2 levels that was accompanied by a transient (<24 >h) increase …

Vitamin D Status And Risk Of Incident Tuberculosis Disease: A Nested Case-Control Study, Systematic Review, And Individual-Participant Data Meta-Analysis, Omowunmi Aibana, Chuan-Chin Huang, Said Aboud, Alberto Arnedo-Pena, Mercedes C. Becerra, Juan Bautista Bellido-Blasco, Ramesh Bhosale, Roger Calderon, Rabia Hussain, Najeeha Talat Iqbal

Department of Pathology and Laboratory Medicine

Background: Few studies have evaluated the association between preexisting vitamin D deficiency and incident tuberculosis (TB). We assessed the impact of baseline vitamins D levels on TB disease risk.
Methods and Findings: We assessed the association between baseline vitamin D and incident TB in a prospective cohort of 6,751 HIV-negative household contacts of TB patients enrolled between September 1, 2009, and August 29, 2012, in Lima, Peru. We screened for TB disease at 2, 6, and 12 months after enrollment. We defined cases as household contacts who developed TB disease at least 15 days after enrollment of the index patient. …

A Population Pharmacokinetic Model For Simvastatin And Its Metabolites In Children And Adolescents., Kayode Ogungbenro, Jonathan B. Wagner, Susan M. Abdel-Rahman, J Steven Leeder, Aleksandra Galetin

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: Poor adherence to dietary/behaviour modifications as interventions for hypercholesterolemia in paediatric patients often necessitates the initiation of statin therapy. The aim of this study was to develop a joint population pharmacokinetic model for simvastatin and four metabolites in children and adolescents to investigate sources of variability in simvastatin acid exposure in this patient population, in addition to SLCO1B1 genotype status.

METHODS: Plasma concentrations of simvastatin and its four metabolites, demographic and polymorphism data for OATP1B1 and CYP3A5 were analysed utilising a population pharmacokinetic modelling approach from an existing single oral dose (10 mg < 17 years and 20 mg ≥ 18 years) pharmacokinetic dataset of 32 children and adolescents.

RESULTS: The population PK model included …

Obstetric And Neonatal Complications Among Women With Autoimmune Disease, Andrew Williams, Katherine Grantz, Indulaxmi Seeni, Candace Robledo, Shanshan Li, Marion Ouidir, Carrie Nobles, Pauline Mendola

School of Medicine Publications

Background: The impact of autoimmune diseases on pregnancy remains understudied on a population level. Examination of obstetric and neonatal outcomes among women with autoimmune disease and their infants can provide important insights for clinical management.

Methods: Autoimmune diseases and outcomes were identified using medical records. Cesarean delivery, preterm birth, preeclampsia, small for gestational age (SGA), neonatal intensive care (NICU) admission, neonatal respiratory distress syndrome (RDS), and perinatal mortality risk was assessed. Poisson regression with robust standard errors estimated relative risks (RR) and 95% confidence intervals (95% CI) with adjustment for maternal characteristics and other chronic conditions.

Results: Women with …

A Comparison Of Lung Function Values Among A Scuba Diver Population And In Comparison To A Non-Diver Population, Gabriel C. Hutson, Jeremy D. Rentsch, Erin M. Eaton

Journal of the South Carolina Academy of Science

The purpose of this study was to investigate possible correlations between lung function values (PEF, IRV, ERV, and FVC) among a diver population, as well as in comparison to a non-diver population. Independent variables for both populations were biological sex, age, and weekly physical activity. Independent variables for the diver population were dive tenure, number of logged dives, certification level, and gas mixture used. A spirometry test was conducted to collect lung function values of both populations. Data from this study suggest a statistically significant relationship between diver and non-diver sex and FVC, diver age and ERV, diver sex and …

Smart Lighting Clinical Testbed Pilot Study On Circadian Phase Advancement, Joseph D. Gleason, Meeko Oishi, Michelle Simkulet, Arunas Tuzikas, John P. Hanifin, George C. Brainard, S. R.J. Brueck, Robert F. Karlicek, Jr., Lee K. Brown

Department of Neurology Faculty Papers

Objective: Lighting is a strong synchronizer for circadian rhythms, which in turn drives a wide range of biological functions. The objective of our work is a) to construct a clinical in-patient testbed with smart lighting, and b) evaluate its feasibility for use in future clinical studies.

Methods: A feedback capable, variable spectrum lighting system was installed at the University of New Mexico Hospital. The system consists of variable spectrum lighting troffers, color sensors, occupancy sensors, and computing and communication infrastructure. We conducted a pilot study to demonstrate proof of principle, that 1) this new technology is capable of providing continuous …

Activation Of Lxrβ Inhibits Tumor Respiration And Is Synthetically Lethal With Bcl-Xl Inhibition, Trang Thi Thu Nguyen, Chiaki Tsuge Ishida, Enyuan Shang, Chang Shu, Consuelo Torrini, Yiru Zhang, Elena Bianchetti, Maria J. Sanchez-Quintero, Giulio Kleiner, Catarina M. Quinzii, Mike-Andrew Westhoff, Georg Karpel-Massler, Peter Canoll, Markus D. Siegelin

Publications and Research

Liver-X-receptor (LXR) agonists are known to bear anti-tumor activity. However, their efficacy is limited and additional insights regarding the underlying mechanism are necessary. By performing transcriptome analysis coupled with global polar metabolite screening, we show that LXR agonists, LXR623 and GW3965, enhance synergistically the anti-proliferative effect of BH3 mimetics in solid tumor malignancies, which is predominantly mediated by cell death with features of apoptosis and is rescued by exogenous cholesterol. Extracellular flux analysis and carbon tracing experiments (U-¹³C-glucose and U-¹³C-glutamine) reveal that within 5 h, activation of LXRβ results in reprogramming of tumor cell metabolism, leading …

Effects Of Obesity And Fall Risk On Gait And Posture Of Community-Dwelling Older Adults, Thurmon E. Lockhart, Christopher W. Frames, Rahul Soangra, Abraham Lieberman

Physical Therapy Faculty Articles and Research

Epidemiological studies link increased fall risk to obesity in older adults, but the mechanism through which obesity increases falls and fall risks is unknown. This study investigates if obesity (Body Mass Index: BMI>30 kg/m2) influenced gait and standing postural characteristics of community dwelling older adults leading to increased risk of falls. One hundred healthy older adults (age 74.0±7.6 years, range of 56-90 years) living independently in a community participated in this study. Participants’ history of falls over the previous two years was recorded, with emphasis on frequency and characteristics of falls. Participants with at least two falls in the …

Liquid Biopsy-Based Single-Cell Metabolic Phenotyping Of Lung Cancer Patients For Informative Diagnostics., Ziming Li, Zhuo Wang, Yin Tang, Xiang Lu, Jie Chen, Yu Dong, Baojun Wu, Chunying Wang, Liu Yang, Zhili Guo, Min Xue, Shun Lu, Wei Wei, Qihui Shi

Articles, Abstracts, and Reports

Accurate prediction of chemo- or targeted therapy responses for patients with similar driver oncogenes through a simple and least-invasive assay represents an unmet need in the clinical diagnosis of non-small cell lung cancer. Using a single-cell on-chip metabolic cytometry and fluorescent metabolic probes, we show metabolic phenotyping on the rare disseminated tumor cells in pleural effusions across a panel of 32 lung adenocarcinoma patients. Our results reveal extensive metabolic heterogeneity of tumor cells that differentially engage in glycolysis and mitochondrial oxidation. The cell number ratio of the two metabolic phenotypes is found to be predictive for patient therapy response, physiological …

Development Of Substrate Degradation Enzyme Therapy For Mucopolysaccharidosis Iva Murine Model., Kazuki Sawamoto, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Mucopolysaccharidosis IVA (MPS IVA) is caused by a deficiency of the lysosomal enzyme N-acetylgalactosamine-6-sulfate sulfatase (GALNS). Conventional enzyme replacement therapy (ERT) is approved for MPS IVA. However, the fact that the infused enzyme cannot penetrate avascular lesions in cartilage leads to minimal impact on the bone lesion. Moreover, short half-life, high cost, instability, and narrow optimal pH range remain unmet challenges in ERT. Thermostable keratanase, endo-β-N-acetylglucosaminidase, has a unique character of a wide optimal pH range of pH 5.0-7.0. We hypothesized that this endoglycosidase degrades keratan sulfate (KS) polymer in circulating blood and, therefore, ameliorates the accumulation of KS in …

A Renal Cell Carcinoma With Biallelic Somatic Tsc2 Mutation: Clinical Study And Literature Review., Jian Pang, Linang Wang, Jing Xu, Qiubo Xie, Qiuli Liu, Dali Tong, Gaolei Liu, Yiqiang Huang, Xingxia Yang, Jinhong Pan, Xiaochu Yan, Qiang Ma, Dianzheng Zhang, Jun Jiang

PCOM Scholarly Works

OBJECTIVES: To elucidate the effect of the biallelic somatic TSC2 mutations, identified in one adolescent patient, in renal cell carcinoma (RCC).

METHODS: Mutation analyses, immunohistochemistry and real-time polymerase chain reaction (PCR) were conducted.

RESULTS: Two novel somatic mutations of TSC2 in unilateral and solitary RCC samples from a 14-year-old female were identified. The pathological features suggest the tumor as a clear-cell renal cell carcinoma. In addition, immunohistochemistry revealed elevated levels of phosphorylated S6K1. Results from in vitro cellular experiments suggest that the mutant TSC2 proteins were quickly degraded and they failed to repress the phosphorylation of S6K1 and STAT3, which …

Mechanisms Of Simvastatin Myotoxicity: The Role Of Autophagy Flux Inhibition., Arya Emami, Shahla Shojaei, Simone C. Da Silva Rosa, Mahmoud Aghaei, Ehsan Samiei, Amir Reza Vosoughi, Forouh Kalantari, Philip Kawalec, James Thliveris, Pawan Sharma, Amir A. Zeki, Mohsen Akbari, Joseph W. Gordon, Saeid Ghavami

Center for Translational Medicine Faculty Papers

Statins are some of the most widely used drugs worldwide, but one of their major side effects is myotoxicity. Using mouse myoblast (C2C12) and human alveolar rhabdomyosarcoma cell lines (RH30) in both 2-dimensional (2D) and 3-dimensional (3D) cell culture, we investigated the mechanisms of simvastatin's myotoxicity. We found that simvastatin significantly reduced cell viability in C2C12 cells compared to RH30 cells. However, simvastatin induced greater apoptosis in RH30 compared to C2C12 cells. Simvastatin-induced cell death is dependent on geranylgeranyl pyrophosphate (GGPP) in C2C12 cells, while in RH30 cells it is dependent on both farnesyl pyrophosphate (FPP) and GGPP. Simvastatin inhibited …