Digital Commons Network^™

Myricetin Inhibits Proliferation Of Cisplatin-Resistant Cancer Cells Through A P53-Dependent Apoptotic Pathway, Haizhi Huang, Allen Y. Chen, Xingqian Ye, Bingyun Li, Yon Rojanasakul, Gary O. Rankin, Yi Charlie Chen

Pharmacology, Physiology and Toxicology

Cisplatin is a commonly used drug for cancer treatment by crosslinking DNA, leading to apoptosis of cancer cells, resistance to cisplatin treatment often occurs, leading to relapse. Therefore, there is a need for the development of more effective treatment strategies that can overcome chemoresistance. Myricetin is a flavonoid from fruits and vegetables, showing anticancer activity in various cancer cells. In this study, we found myricetin exhibited greater cytotoxicity than cisplatin in two cisplatin-resistant ovarian cancer cell lines, OVCAR-3 and A2780/CP70, and it was less cytotoxic to the normal ovarian cell line IOSE-364. Myricetin selectively induced apoptosis in both cisplatinresistant cancer …

The P53 Tumor Suppressor Protein Protects Against Chemotherapeutic Stress And Apoptosis In Human Medulloblastoma Cells., Sarah Waye, Aisha Naeem, Muhammad Umer Choudhry, Erika Parasido, Lucas Tricoli, Brian R. Rood, +6 Additional Authors

Pediatrics Faculty Publications

Medulloblastoma (MB), a primitive neuroectodermal tumor, is the most common malignant childhood brain tumor and remains incurable in about a third of patients. Currently, survivors carry a significant burden of late treatment effects. The p53 tumor suppressor protein plays a crucial role in influencing cell survival in response to cellular stress and while the p53 pathway is considered a key determinant of anti-tumor responses in many tumors, its role in cell survival in MB is much less well defined. Herein, we report that the experimental drug VMY-1-103 acts through induction of a partial DNA damage-like response as well induction of …

Women With Disabilities: Reproductive Care And Women’S Health, Stephanie Stockburger, Hatim A. Omar

Pediatrics Faculty Publications

Children, adolescents, and women with disabilities experience the same sexual development, pubertal changes, concerns, and desire to reproduce as their typically developing counterparts. However, society has tended to stigmatize women with disabilities as “asexual” and ignore this aspect of their health care. These women are less likely to receive gynecological exams, contraception, and evaluation of sexual dysfunction. Unfortunately, having a disability places women at risk for sexual exploitation and abuse as well as sexually transmitted infections. Therefore, reproductive health care for these women is imperative. A number of barriers to receiving reproductive care exist. However, with proper education and knowledge …

Dietary Almonds Increase Serum Hdl Cholesterol In Coronary Artery Disease Patients In A Randomized Controlled Trial., Humaira Jamshed, Fateh Ali Tipoo Sultan, Romaina Iqbal, Anwar Gilani

Section of Cardiology

Background: More than one-half of coronary artery disease (CAD) patients have low HDL cholesterol despite having well-managed LDL cholesterol. Almond supplementation has not been shown to elevate circulating HDL cholesterol concentrations in clinical trials, perhaps because the baseline HDL cholesterol of trial subjects was not low.

Objective: This clinical trial was designed to test the effect of almond supplementation on low HDL cholesterol in CAD patients.

Methods: A total of 150 CAD patients (50 per group), with serum LDL cholesterol ≤100 mg/dL and HDL cholesterol ≤40 mg/dL in men and ≤50 mg/dL in women, were recruited from the Aga Khan …

Isoniazid Induced Motor-Dominant Neuropathy, Rabeeya Arsalan, Saniya Sabzwari

Department of Family Medicine

Isoniazid though a very effective treatment for tuberculosis can cause severe motor-dominant neuropathy which can be reversible with pyridoxine supplementation. A 45-year-old female diagnosed with psoas abscess, culture positive for mycobacterium tuberculosis, was started on anti- tuberculous treatment with four drugs, including isoniazid at a dose of 5 mg/kg/day. Three months later she developed severe motor weakness of lower limbs with loss of ankle and knee reflexes. She was treated with vitamin B6 injections and isoniazid treatment was continued. Her motor weakness gradually improved in a few months, but mild sensory impairment persisted even after two years. There is need …

Parasite Manipulation Of The Invariant Chain And The Peptide Editor H2-Dm Affects Major Histocompatibility Complex Class Ii Antigen Presentation During Toxoplasma Gondii Infection, Louis-Philippe Leroux, Manami Nishi, Sandy El-Hage, Barbara A. Fox, David I Bzik, Florence Dzierszinsk

Dartmouth Scholarship

Toxoplasma gondii is an obligate intracellular protozoan parasite. This apicomplexan is the causative agent of toxoplasmosis, a leading cause of central nervous system disease in AIDS. It has long been known that T. gondii interferes with major histocompatibility complex class II (MHC-II) antigen presentation to attenuate CD4(+) T cell responses and establish persisting infections. Transcriptional downregulation of MHC-II genes by T. gondii was previously established, but the precise mechanisms inhibiting MHC-II function are currently unknown. Here, we show that, in addition to transcriptional regulation of MHC-II, the parasite modulates the expression of key components of the MHC-II antigen presentation pathway, …

Impact Of Environmental Health On Teen Outcomes In Rural Kentucky, Lesley Davidson, Alissa Briggs, Hatim A. Omar

Pediatrics Faculty Publications

Understanding the impact of family dynamics on health has become an environmental health priority in the field of adolescent medicine. Family dynamics are much more complex than they were 60 years ago and so are behavioral outcomes. This transformation in the American family has led towards a large array of adolescent living situations. Rural Kentucky is a prime example of an area with a high rate of non-traditional family composition. Poor family dynamics may be associated with increased rates of high risk behaviors among teenagers. Among these behaviors are drug use, sexual activity, and depression. In this study, we evaluated …

A Phase 3 Trial Of 2 Years Of Androgen Suppression And Radiation Therapy With Or Without Adjuvant Chemotherapy For High-Risk Prostate Cancer: Final Results Of Radiation Therapy Oncology Group Phase 3 Randomized Trial Nrg Oncology Rtog 9902., Seth A. Rosenthal, Daniel Hunt, A. Oliver Sartor, Kenneth J. Pienta, Leonard G. Gomella, David Grignon, Raghu Rajan, Kevin J. Kerlin, Christopher U. Jones, Michael Dobelbower, William U Shipley, Kenneth Zeitzer, Daniel A. Hamstra, Viroon Donavanik, Marvin Rotman, Alan C. Hartford, Jeffrey Michalski, Michael Seider, Harold Kim, Deborah A. Kuban, Jennifer Moughan, Howard Sandler

Department of Urology Faculty Papers

PURPOSE: Long-term (LT) androgen suppression (AS) with radiation therapy (RT) is a standard treatment of high-risk, localized prostate cancer (PCa). Radiation Therapy Oncology Group 9902 was a randomized trial testing the hypothesis that adjuvant combination chemotherapy (CT) with paclitaxel, estramustine, and oral etoposide plus LT AS plus RT would improve overall survival (OS).

METHODS AND MATERIALS: Patients with high-risk PCa (prostate-specific antigen 20-100 ng/mL and Gleason score [GS] ≥ 7 or clinical stage ≥ T2 and GS ≥ 8) were randomized to RT and AS (AS + RT) alone or with adjuvant CT (AS + RT + CT). CT was …

Fsd-C10: A More Promising Novel Rock Inhibitor Than Fasudil For Treatment Of Cns Autoimmunity., Yan-Le Xin, Jie-Zhong Yu, Xin-Wang Yang, Chun-Yun Liu, Yan-Hua Li, Ling Feng, Zhi Chai, Wan-Fang Yang, Qing Wang, Wei-Jia Jiang, Guang-Xian Zhang, Bao-Guo Xiao, Cun-Gen Ma

Department of Neurology Faculty Papers

Rho-Rho kinase (Rho-ROCK) triggers an intracellular signalling cascade that regulates cell survival, death, adhesion, migration, neurite outgrowth and retraction and influences the generation and development of several neurological disorders. Although Fasudil, a ROCK inhibitor, effectively suppressed encephalomyelitis (EAE), certain side effects may limit its clinical use. A novel and efficient ROCK inhibitor, FSD-C10, has been explored. In the present study, we present chemical synthesis and structure of FSD-C10, as well as the relationship between compound concentration and ROCK inhibition. We compared the inhibitory efficiency of ROCKI and ROCK II, the cell cytotoxicity, neurite outgrowth and dendritic formation, neurotrophic factors and …

Integrating Meal And Exercise Into Personalized Glucoregulation Models: Metabolic Dynamics And Diabetic Athletes, Sofie Schunk

Master's Theses (2009 -)

Diabetes affects nearly 26 million Americans, according to the American Diabetes Association, with as many as three million Americans who have Type 1 Diabetes (ADA, 2015). Type 1 Diabetes (T1D) is autoimmune and characterized by little to no insulin production whereas Type 2 Diabetes (T2D) concerns insulin resistance and inability to use produced insulin. Factors contributing to current diabetes management and regulation include exercise type, daily movement activities, and distinct tissue compartment metabolism, each challenging to model in a robust and comprehensive manner. Past models are highly limited in regard to exercise and varying glucose fluctuations dependent on type, intensity, …

Short Term Outcome And Predictors Of Response To Neoadjuvant Treatment In Rectal Cancer, Rizwan Sultan, Tabish Chawla, Mirza Mirza Aman Beg

Department of Surgery Docs

Abstract

OBJECTIVE:

To evaluate response to neoadjuvant chemoradiation in the treatment of rectal cancer and to see if it can be predicted whether a particular patient will benefit from such treatment.

METHODS:

The retrospective case series was done at the Aga Khan University Hospital, Karachi, and comprised data related to period from January 2005 to December 2014 of patients with rectal cancer who had received neoadjuvant treatment. They were divided into responders and non-responders on the basis of imaging. Pre-treatment factors were compared to identify differences in the two groups. SPSS 19 was used for statistical analysis.

RESULTS:

The median …

Orphan Nuclear Receptor Nur77 Inhibits Cardiac Hypertrophic Response To Beta-Adrenergic Stimulation., Guijun Yan, Ni Zhu, Shengdong Huang, Bing Yi, Xiying Shang, Ming Chen, Nadan Wang, Guan-Xin Zhang, Jennifer A Talarico, Douglas G Tilley, Erhe Gao, Jianxin Sun

Center for Translational Medicine Faculty Papers

The orphan nuclear receptor Nur77 plays critical roles in cardiovascular diseases, and its expression is markedly induced in the heart after beta-adrenergic receptor (β-AR) activation. However, the functional significance of Nur77 in β-AR signaling in the heart remains unclear. By using Northern blot, Western blot, and immunofluorescent staining assays, we showed that Nur77 expression was markedly upregulated in cardiomyocytes in response to multiple hypertrophic stimuli, including isoproterenol (ISO), phenylephrine (PE), and endothelin-1 (ET-1). In a time- and dose-dependent manner, ISO increases Nur77 expression in the nuclei of cardiomyocytes. Overexpression of Nur77 markedly inhibited ISO-induced cardiac hypertrophy by inducing nuclear translocation …

Janus Kinase 2/Signal Transducer And Activator Of Transcription 3 Inhibitors Attenuate The Effect Of Cardiotrophin-Like Cytokine Factor 1 And Human Focal Segmental Glomerulosclerosis Serum On Glomerular Filtration Barrier., Mukut Sharma, Jianping Zhou, Jean-François Gauchat, Ram Sharma, Ellen T. Mccarthy, Tarak Srivastava, Virginia J. Savin

Manuscripts, Articles, Book Chapters and Other Papers

Recurrence of idiopathic focal segmental glomerulosclerosis (FSGS) after renal transplantation is believed to be caused by a circulating factor(s). We detected cardiotrophin-like cytokine factor 1 (CLCF1), a member of the interleukin 6 family, in the plasma from patients with recurrent FSGS. We hypothesized that CLCF1 contributes to the effect of FSGS serum on the glomerular filtration barrier in vitro. Presently, we studied the effect of CLCF1 on isolated rat glomeruli using an in vitro assay of albumin permeability (P(alb)). CLCF1 (0.05-100 ng/mL) increased P(alb) and caused maximal effect at 5-10 ng/mL (P < 0.001). The increase in Palb was analogous to the effect of FSGS serum. Anti-CLCF1 monoclonal antibody blocked the CLCF1-induced increase in P(alb) and significantly attenuated the effect of FSGS serum (P < 0.001). The heterodimer composed of CLCF1 and cosecreted molecule cytokine receptor-like factor 1 (CRLF1) attenuated the increase in P(alb) caused by CLCF1 or FSGS serum. Western blot analysis showed that CLCF1 upregulated phosphorylation of signal transducer and activator of transcription 3 (STAT3) (Tyr705) in glomeruli. This effect was diminished by the heterodimer CLCF1-CRLF1. Janus kinase 2 (JAK2) inhibitor BMS-1119543 or STAT3 inhibitor Stattic significantly blocked the effect of CLCF1 or FSGS serum on P(alb) (P < 0.001). These novel findings suggest that when monomeric CLCF1 increases P(alb), the heterodimer CLCF1-CRLF1 may protect the glomerular filtration barrier. We speculate that albuminuria in FSGS is related to qualitative or quantitative changes in the CLCF1-CRLF1 complex, and that JAK2 or STAT3 inhibitors may be novel therapeutic agents to treat FSGS.

Deubiquitinase Usp47/Ubp64e Regulates Β-Catenin Ubiquitination And Degradation And Plays A Positive Role In Wnt Signaling, Jiandang Shi, Yajuan Liu, Xuehe Xu, Wen Zhang, Tianxin Yu, Jianhang Jia, Chunming Liu

Markey Cancer Center Faculty Publications

Wnt signaling plays important roles in development and tumorigenesis. A central question about the Wnt pathway is the regulation of β-catenin. Phosphorylation of β-catenin by CK1α and GSK3 promotes β-catenin binding to β-TrCP, leading to β-catenin degradation through the proteasome. The phosphorylation and ubiquitination of β-catenin have been well characterized; however, it is unknown whether and how a deubiquitinase is involved. In this study, by screening RNA interference (RNAi) libraries, we identified USP47 as a deubiquitinase that prevents β-catenin ubiquitination. Inactivation of USP47 by RNAi increased β-catenin ubiquitination, attenuated Wnt signaling, and repressed cancer cell growth. Furthermore, USP47 deubiquitinates itself, …

Iv And Ip Administration Of Rhodamine In Visualization Of Wbc-Bbb Interactions In Cerebral Vessels., Zachary Wilmer Reichenbach, Hongbo Li, John P. Gaughan, Melanie B. Elliott, Ronald Tuma

Department of Neurosurgery Faculty Papers

Epi-illuminescence intravital fluorescence microscopy has been employed to study leukocyte-endothelial interactions in a number of brain pathologies. Historically, dyes such as Rhodamine 6G have been injected intravenously. However, intravenous injections can predispose experimental animals to a multitude of complications and requires a high degree of technical skill. Here, we study the efficacy of injecting Rhodamine 6G into the peritoneum (IP) for the purpose of analyzing leukocyte-endothelial interactions through a cranial window during real time intravital microscopy. After examining the number of rolling and adherent leukocytes through a cranial window, we found no advantage to the intravenous injection (IV). Additionally, we …

Monitoring Human Growth And Development: A Continuum From The Womb To The Classroom, José Villar, Aris T. Papageorghiou, Ruyan Pang, Laurent J. Salomon, Ana Langer, Cesar Victora, Manorama Purwar, Cameron Chumlea, Wu Qingqing, Sicco A. Scherjon, Fernando C. Barros, Maria Carvalho, Douglas G. Altman, Francesca Giuliani, Enrico Bertino, Yasmin A. Jaffer, Leila Cheikh Ismail, Eric O. Ohuma, Ann Lambert, J. Alison Noble, Michael G. Gravett, Zulfiqar A. Bhutta, Stephen H. Kennedy

Obstetrics and Gynaecology, East Africa

A comprehensive set of fully integrated anthropometric measures is needed to evaluate human growth from conception to infancy so that consistent judgments can be made about the appropriateness of fetal and infant growth. At present, there are 2 barriers to this strategy. First, descriptive reference charts, which are derived from local, unselected samples with inadequate methods and poor characterization of their putatively healthy populations, commonly are used rather than prescriptive standards. The use of prescriptive standards is justified by the extensive biologic, genetic, and epidemiologic evidence that skeletal growth is similar from conception to childhood across geographic populations, when health, …

Intra-Individual Consistency In Endocrine Profiles Across Successive Pregnancies, Molly Fox, Curt A. Sandman, Elyssia Poggi Davis, Laura M. Glynn

Psychology Faculty Articles and Research

Context: It is yet unknown how similar women’s hormone levels are during successive pregnancies, and very little is known about the degree to which siblings experience similar prenatal environments. Given the importance of understanding how women’s reproductive life-histories exert cumulative effects on health via hormone exposure, and the importance of understanding how fetal programming via endocrine signaling affects sibling trait concordance, here we address this important lacuna in the literature.

Objective: To investigate how consistent are women’s hormone profiles across two successive pregnancies.

Design and Main Outcome Measures: This longitudinal, prospective study followed a cohort of 28 …

Characterization Of 1577 Primary Prostate Cancers Reveals Novel Biological And Clinicopathologic Insights Into Molecular Subtypes., Scott A. Tomlins, Mohammed Alshalalfa, Elai Davicioni, Nicholas Erho, Kasra Yousefi, Shuang Zhao, Zaid Haddad, Robert B. Den, Adam P. Dicker, Bruce J. Trock, Angelo M. Demarzo, Ashley E. Ross, Edward M. Schaeffer, Eric A. Klein, Cristina Magi-Galluzzi, R. Jeffrey Karnes, Robert B. Jenkins, Felix Y. Feng

Department of Radiation Oncology Faculty Papers

BACKGROUND: Prostate cancer (PCa) molecular subtypes have been defined by essentially mutually exclusive events, including ETS gene fusions (most commonly involving ERG) and SPINK1 overexpression. Clinical assessment may aid in disease stratification, complementing available prognostic tests.

OBJECTIVE: To determine the analytical validity and clinicopatholgic associations of microarray-based molecular subtyping.

DESIGN, SETTING, AND PARTICIPANTS: We analyzed Affymetrix GeneChip expression profiles for 1577 patients from eight radical prostatectomy cohorts, including 1351 cases assessed using the Decipher prognostic assay (GenomeDx Biosciences, San Diego, CA, USA) performed in a laboratory with Clinical Laboratory Improvements Amendment certification. A microarray-based (m-) random forest ERG classification model …

A Randomized Controlled Behavioral Intervention Trial To Improve Medication Adherence In Adult Stroke Patients With Prescription Tailored Short Messaging Service (Sms)-Sms4stroke Study., Ayeesha Kamran Kamal, Quratulain Shaikh,, Omrana Pasha, Iqbal Azam Syed, Muhammad Islam,, Adeel Ali Memon, Hasan Rehman, Masood Ahmed Akram,, Muhammad Affan, Sumaira Nazir, Salman Aziz, Muhammad Jan, Anita Andani, Abdul Muqeet, Bilal Ahmed, Shariq Khoja

Department of Medicine

Background: The effectiveness of mobile technology to improve medication adherence via customized Short Messaging Service (SMS) reminders for stroke has not been tested in resource poor areas. We designed a randomized controlled trial to test the effectiveness of SMS on improving medication adherence in stroke survivors in Pakistan.

Methods: This was a parallel group, assessor-blinded, randomized, controlled, superiority trial. Participants were centrally randomized in fixed block sizes. Adult participants on multiple medications with access to a cell phone and stroke at least 4 weeks from onset (Onset as defined by last seen normal) were eligible. The intervention group, in addition …

Severity Of Depression, Anxious Distress And The Risk Of Cardiovascular Disease In A Swedish Population-Based Cohort., Aysha Almas, Yvonne Forsell,, Romaina Iqbal, Imre Janszky,, Jette Moller

Department of Medicine

Background: Depression is known to be associated with cardiovascular diseases (CVD). This population-based cohort study aimed to determine the association between depression of varying severity and risk for CVD and to study the effect of concomitant anxious distress on this association.

Methods: We utilized data from a longitudinal cohort study of mental health, work and relations among adults (20–64 years), with a total of 10,443 individuals. Depression and anxious distress were assessed using psychiatric rating scales and defined according to DSM-5. Outcomes were register-based and self-reported cardiovascular diseases.

Findings: Overall increased odds ratios of 1.5 to 2.6 were seen …

Caffeine And Progression Of Parkinson Disease: A Deleterious Interaction With Creatine., David K. Simon, Cai Wu, Barbara C. Tilley, Anne-Marie Wills, Michael J. Aminoff, Jacquelyn Bainbridge, Robert A. Hauser, Jay S. Schneider, Saloni Sharma, Carlos Singer, Caroline M. Tanner, Daniel Truong, Pei Shieen Wong

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

OBJECTIVE: Increased caffeine intake is associated with a lower risk of Parkinson disease (PD) and is neuroprotective in mouse models of PD. However, in a previous study, an exploratory analysis suggested that, in patients taking creatine, caffeine intake was associated with a faster rate of progression. In the current study, we investigated the association of caffeine with the rate of progression of PD and the interaction of this association with creatine intake.

METHODS: Data were analyzed from a large phase 3 placebo-controlled clinical study of creatine as a potentially disease-modifying agent in PD. Subjects were recruited for this study from …

Increased Expression Of Napdh Oxidase 4 In Systemic Sclerosis Dermal Fibroblasts: Regulation By Transforming Growth Factor Β., Sonsoles Piera-Velazquez, Alma Makul, Sergio A. Jimenez

Department of Dermatology and Cutaneous Biology Faculty Papers

OBJECTIVE: Systemic sclerosis (SSc) is characterized by severe and often progressive fibrosis of the skin and multiple internal organs. The mechanisms responsible for these alterations remain obscure, although excessive reactive oxygen species (ROS)-mediated oxidative stress has been implicated. NOX-4 is 1 of 7 isoforms of NADPH oxidase responsible for the generation of ROS. The purpose of this study was to examine NOX-4 expression in skin and cultured dermal fibroblasts from SSc patients and to examine its regulation by transforming growth factor β1 (TGFβ1).

METHODS: NOX-4 was assessed in normal and SSc skin by immunohistologic analysis and in normal and SSc …

Hereditary Sensory Autonomic Neuropathy Ii, A Rare Disease In A Large Pakistani Family, Fazal M. Arain, Prem Chand

Department of Paediatrics and Child Health

Hereditary Sensory Autonomic Neuropathy II (HSAN II) is a rare genetic disorder, characterized by severe loss of pain, temperature and touch sensation. Injuries in these patients can progress to necrosis and shedding of digits and limbs. Here we report two cases of HSAN II belonging to a Pakistani family. Individual 1, a forty five year old man, had complete loss of pain sensation since birth. Self-mutilation and complication of injuries resulted in the shedding of all the digits and right foot and surgical amputation of left leg. Individual 2, a five year old girl,had delay in healing of wounds and …

Congenital Factor Vii Deficiency In Children At Tertiary Health Care Facility In Pakistan, Muhammad Matloob Alam, Bushra Moiz, Karim Abdur Rehman, Priyanka Jethwani, Zehra Fadoo

Department of Paediatrics and Child Health

This study presents the demographics, clinical spectrum, and outcome of patients with congenital factor VII (FVII) deficiency at a tertiary care center over a period of 12 years. Of the 49 patients, 27 (55%) patients were males. Consanguinity was found in 92% of the patients. The median age of symptom onset was 2.4 (interquartile range [IQR]: 1.1-6.5) years with a median age of 5.8 (IQR: 3.1-10) years at diagnosis. Life-threatening complications like intracranial bleeding (ICB) and intra-abdominal bleeding (IAB) were observed in 8 (16.4%) patients. We found that 11 (55%) of the 20 patients with FVII coagulant activity (FVIIc) 5% …

Efficacy Of Oral Anticoagulation In Stroke Prevention Among Sinus-Rhythm Patients Who Lack Left Atrial Mechanical Contraction After Cryoablation, José Martínez-Comendador, Javier Gualis, José Miguel Marcos-Vidal, Jonnatan Buber, Carlos Esteban Martín, Jesús Gomez-Plana, Miguel Angel Rodríguez, Ignacio Iglesias-Garriz, David Alonso, Carlos Soria, Eva Higuera Miguélez, Mario Castaño

The Texas Heart Institute Journal

The customary recommendation is that oral anticoagulation be withdrawn a few months after cryoablation for atrial fibrillation, independently of left atrial mechanical contraction in patients in sinus rhythm. Recently, a 5-fold increase in stroke has been described in sinus-rhythm patients who lack atrial mechanical contraction. One aim of this study was to evaluate the efficacy of oral anticoagulation in preventing postoperative stroke in such patients.

This prospective study divided 154 sinus-rhythm patients into 2 groups, depending on the presence (108 patients) or absence (46 patients) of left atrial mechanical contraction at 6 months after surgery, and monitored them annually for …

Proporsi Infeksi Virus Hepatitis B Tersamar Pada Pasien Yang Terinfeksi Human Immunodeficiency Virus, Joyce Bratanata, Rino Alvani Gani, Teguh Haryono Karjadi

Jurnal Penyakit Dalam Indonesia

Pendahuluan. Infeksi hati kronik merupakan penyebab penting morbiditas serta mortalitas di antara penderita HIV positif pada pemakaian highly active antiretroviral therapies (HAART). Penyakit hati kronik dapat terjadi mulai dari infeksi tersamar sampai karsinoma hepatoselular. Kejadian VHB tersamar sering ditemukan pada pasien dengan kondisi imunosupresi seperti HIV. Penelitian ini bertujuan untuk mengetahui besarnya proporsi hepatitis B tersamar, hitung CD4+, transmisi IVDU, proporsi hepatitis C dan proporsi anti-HBc yang positif pada koinfeksi hepatitis B tersamar pada pasien HIV/AIDS di RSCM.

Metode. Studi potong-lintang dilakukan pada pasien HIV yang berobat di Pokdisus dan ruang rawat inap RSCM dengan pengambilan sampel secara …

Targeting The Mrna-Binding Protein Hur Impairs Malignant Characteristics Of Pancreatic Ductal Adenocarcinoma Cells., Masaya Jimbo, Fernando F Blanco, Yu-Hung Huang, Aristeidis G Telonis, Brad A Screnci, Gabriela L Cosma, Vitali Alexeev, Gregory E Gonye, Charles Yeo, Janet A Sawicki, Jordan M Winter, Jonathan Brody, Md

Computational Medicine Center Faculty Papers

Post-transcriptional regulation is a powerful mediator of gene expression, and can rapidly alter the expression of numerous transcripts involved in tumorigenesis. We have previously shown that the mRNA-binding protein HuR (ELAVL1) is elevated in human pancreatic ductal adenocarcinoma (PDA) specimens compared to normal pancreatic tissues, and its cytoplasmic localization is associated with increased tumor stage. To gain a better insight into HuR's role in PDA biology and to assess it as a candidate therapeutic target, we altered HuR expression in PDA cell lines and characterized the resulting phenotype in preclinical models. HuR silencing by short hairpin and small interfering RNAs …

Novel Targeted Sirna-Loaded Hybrid Nanoparticles: Preparation, Characterization And In Vitro Evaluation., Nneka Dim, Maryna Perepelyuk, Olukayode Gomes, Chellappagounder Thangavel, Yi Liu, Robert Den, Ashakumary Lakshmikuttyamma, Sunday A Shoyele

Department of Radiation Oncology Faculty Papers

BACKGROUND: siRNAs have a high potential for silencing critical molecular pathways that are pathogenic. Nevertheless, their clinical application has been limited by a lack of effective and safe nanotechnology-based delivery system that allows a controlled and safe transfection to cytosol of targeted cells without the associated adverse effects. Our group recently reported a very effective and safe hybrid nanoparticle delivery system composing human IgG and poloxamer-188 for siRNA delivery to cancer cells. However, these nanoparticles need to be optimized in terms of particle size, loading capacity and encapsulation efficiency. In the present study, we explored the effects of certain production …

Lipin1 Regulates Skeletal Muscle Differentiation Through Extracellular Signal-Regulated Kinase (Erk) Activation And Cyclin D Complex-Regulated Cell Cycle Withdrawal, Weihua Jiang, Jing Zhu, Xun Zhuang, Xiping Zhang, Tao Luo, Karyn Esser, Hongmei Ren

Saha Cardiovascular Research Center Faculty Publications

Lipin1, an intracellular protein, plays critical roles in controlling lipid synthesis and energy metabolism through its enzymatic activity and nuclear transcriptional functions. Several mouse models of skeletal muscle wasting are associated with lipin1 mutation or altered expression. Recent human studies have suggested that children with homozygous null mutations in the LPIN1 gene suffer from rhabdomyolysis. However, the underlying pathophysiologic mechanism is still poorly understood. In the present study we examined whether lipin1 contributes to regulating muscle regeneration. We characterized the time course of skeletal muscle regeneration in lipin1-deficient fld mice after injury. We found that fld mice exhibited smaller regenerated …

Off-Target V(D)J Recombination Drives Lymphomagenesis And Is Escalated By Loss Of The Rag2 C Terminus., Martina Mijušković, Yi-Fan Chou, Vered Gigi, Cory R Lindsay, Olga Shestova, Susanna M Lewis, David B Roth

Cardeza Foundation for Hematologic Research

Genome-wide analysis of thymic lymphomas from Tp53(-/-) mice with wild-type or C-terminally truncated Rag2 revealed numerous off-target, RAG-mediated DNA rearrangements. A significantly higher fraction of these errors mutated known and suspected oncogenes/tumor suppressor genes than did sporadic rearrangements (p < 0.0001). This tractable mouse model recapitulates recent findings in human pre-B ALL and allows comparison of wild-type and mutant RAG2. Recurrent, RAG-mediated deletions affected Notch1, Pten, Ikzf1, Jak1, Phlda1, Trat1, and Agpat9. Rag2 truncation substantially increased the frequency of off-target V(D)J recombination. The data suggest that interactions between Rag2 and a specific chromatin modification, H3K4me3, support V(D)J recombination fidelity. Oncogenic effects of off-target rearrangements created by this highly regulated recombinase may need to be considered in design of site-specific nucleases engineered for genome modification.