Medicine and Health Sciences Commons^™

Inspiration For The Future: The Role Of Inspiratory Muscle Training In Cystic Fibrosis., Ren-Jay Shei, Robert L Dekerlegand, Kelly A Mackintosh, John D Lowman, Melitta A Mcnarry

Department of Physical Therapy Faculty Papers

Cystic fibrosis (CF) is an inherited, multi-system, life-limiting disease characterized by a progressive decline in lung function, which accounts for the majority of CF-related morbidity and mortality. Inspiratory muscle training (IMT) has been proposed as a rehabilitative strategy to treat respiratory impairments associated with CF. However, despite evidence of therapeutic benefits in healthy and other clinical populations, the routine application of IMT in CF can neither be supported nor refuted due to the paucity of methodologically rigorous research. Specifically, the interpretation of available studies regarding the efficacy of IMT in CF is hampered by methodological threats to internal and external …

Incidence Rates Of Critical Low Glucoses (<40 Mg/Dl) By Poct Before And After New Policies For Treatment Of Clinically Significant Hypoglycemia (<54 Mg/Dl): A Comparison Between Two Hospitals, Lilah Evans, Douglas F. Stickle, Barbara Goldsmith

Department of Pathology, Anatomy, and Cell Biology Posters

Glucose <54 mg/dL was recently defined as Clinically Significant Hypoglycemia (CSH, American Diabetes Association, Standards of Medical Care in Diabetes, 2017). In January 2018, our hospitals instituted a callback policy for inpatient CSH from the central laboratory, and instituted a new nursing procedure for response to CSH. We examined whether the new policies had affected the incidence rate of low glucose critical values (CRITICAL, <40 mg/dL) among POCT glucose measurements. This was investigated for two hospitals within our system: A, a 950-bed academic medical center hospital, and B, a 200-bed community hospital.

Identification Of Emergency Care-Sensitive Conditions And Characteristics Of Emergency Department Utilization., Anita A. Vashi, Tracy Urech, Brendan Carr, Liberty Greene, Theodore Warsavage, Renee Hsia, Steven M. Asch

Department of Emergency Medicine Faculty Papers

Importance: Monitoring emergency care quality requires understanding which conditions benefit most from timely, quality emergency care.

Objectives: To identify a set of emergency care-sensitive conditions (ECSCs) that are treated in most emergency departments (EDs), are associated with a spectrum of adult age groups, and represent common reasons for seeking emergency care and to provide benchmark national estimates of ECSC acute care utilization.

Design, Setting, and Participants: A modified Delphi method was used to identify ECSCs. In a cross-sectional analysis, ECSC-associated visits by adults (aged ≥18 years) were identified based on International Statistical Classification of Diseases, Tenth Revision, Clinical Modification diagnosis …

Non-Thermal Plasma-Induced Immunogenic Cell Death In Cancer: A Topical Review., Marian Khalili, Lynsey Daniels, Abraham Lin, Fred C. Krebs, Adam E. Snook, Sander Bekeschus, Wilbur B. Bowne, Vandana Miller

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Recent advances in biomedical research in cancer immunotherapy have identified the use of an oxidative stress-based approach to treat cancers, which works by inducing immunogenic cell death (ICD) in cancer cells. Since the anti-cancer effects of non-thermal plasma (NTP) are largely attributed to the reactive oxygen and nitrogen species that are delivered to and generated inside the target cancer cells, it is reasonable to postulate that NTP would be an effective modality for ICD induction. NTP treatment of tumors has been shown to destroy cancer cells rapidly and, under specific treatment regimens, this leads to systemic tumor-specific immunity. The translational …

Appropriate Therapeutic Drug Monitoring Of Biologic Agents For Patients With Inflammatory Bowel Diseases., Konstantinos Papamichael, Adam S. Cheifetz, Gil Y. Melmed, Peter M. Irving, Niels Vande Casteele, Patricia L. Kozuch, Laura E. Raffals, Leonard Baidoo, Brian Bressler, Shane M. Devlin, Jennifer Jones, Gilaad G. Kaplan, Miles P. Sparrow, Fernando S Velayos, Thomas Ullman, Corey A. Siegel

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND & AIMS: Therapeutic drug monitoring (TDM) is widely available for biologic therapies in patients with inflammatory bowel disease (IBD). We reviewed current data and provided expert opinion regarding the clinical utility of TDM for biologic therapies in IBD.

METHODS: We used a modified Delphi method to establish consensus. A comprehensive literature review was performed regarding the use of TDM of biologic therapy in IBD and presented to international IBD specialists. Subsequently, 28 statements on the application of TDM in clinical practice were rated on a scale of 1 to 10 (1 = strongly disagree and 10 = strongly agree) …

Understanding The Axonal Response To Injury By In Vivo Imaging In The Mouse Spinal Cord: A Tale Of Two Branches., Binhai Zheng, Ariana O Lorenzana, Le Ma

Department of Neuroscience Faculty Papers

Understanding the basic properties of how axons respond to injury in the mammalian central nervous system (CNS) is of fundamental value for developing strategies to promote neural repair. Axons possess complex morphologies with stereotypical branching patterns. However, current knowledge of the axonal response to injury gives little consideration to axonal branches, nor do strategies to promote axon regeneration. This article reviews evidence from in vivo spinal cord imaging that axonal branches markedly impact the degenerative and regenerative responses to injury. At a major bifurcation point, depending on whether one or both axonal branches are injured, neurons may choose either a …

The Case For Patient Navigation In Lung Cancer Screening In Vulnerable Populations: A Systematic Review., Christine S Shusted, Julie A Barta, Michael Lake, Rickie Brawer, Brooke Ruane, Teresa E Giamboy, Baskaran Sundaram, Nathaniel R Evans, Ronald E Myers, Gregory C Kane

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

Patient navigation has been proposed to combat cancer disparities in vulnerable populations. Vulnerable populations often have poorer cancer outcomes and lower levels of screening, adherence, and treatment. Navigation has been studied in various cancers, but few studies have assessed navigation in lung cancer. Additionally, there is a lack of consistency in metrics to assess the quality of navigation programs. The authors conducted a systematic review of published cancer screening studies to identify quality metrics used in navigation programs, as well as to recommend standardized metrics to define excellence in lung cancer navigation. The authors included 26 studies evaluating navigation metrics …

Primary Care Providers' Attitudes And Practices Regarding Cancer Screening In Older Adults., Randa Sifri, Brooke Salzman, Amy Cunningham, Alexis Silverio, Madalene Zale, Christine Talerico

Department of Family & Community Medicine Faculty Papers

Introduction: Cancer-screening decisions for older adults should be individualized. However, conducting such complex shared decisions may be challenging for primary care providers (PCPs). Additionally, there is little information on how PCPs make these decisions. This study consisted of a provider survey and chart review to assess current PCP approaches to breast and colorectal cancer (CRC) screening with patients age ≥75.

Methods: PCP survey questions: panel age, comfort with discussion of screening harms and benefits, screening decision-making process, and discussion style. One Hundred charts were chosen from a random sample of male and female patients ≥75 with a recent office …

Unilateral Enophthalmos., Grace L. Su, Sara E. Lally, Carol L. Shields

Wills Eye Hospital Papers

No abstract provided.

Effects Of The 2017 Clinical Practice Guidelines On Hypertension In Children And Adolescents: A Commentary, Bonita Falkner

Department of Medicine Faculty Papers

No abstract provided.

Prevalence Of Dyskinesia And Off By 30-Minute Intervals Through The Day And Assessment Of Daily Episodes Of Dyskinesia And Off: Novel Analyses Of Diary Data From Gocovri Pivotal Trials., Robert A. Hauser, Daniel Kremens, Lawrence W. Elmer, David L. Kreitzman, Ryan R. Walsh, Reed Johnson, Robert Howard, Jack T. Nguyen, Rajiv Patni

Department of Neurology Faculty Papers

BACKGROUND: Parkinson's disease (PD) patients using levodopa commonly develop dyskinesia and OFF episodes that reduce quality of life.

OBJECTIVE: Evaluate prevalence of troublesome dyskinesia and OFF through the day, assessed by 30-minute intervals, as well as the mean number and duration of troublesome dyskinesia and OFF episodes, transitions between PD states, and effects of Gocovri® (amantadine) extended release capsules on these episodes.

METHODS: Evaluate diary data from pooled Gocovri phase 3, placebo-controlled trials-analyzed for 17 hours following wake-up-at baseline and week 12.

RESULTS: Diaries were evaluable for 162 patients. At baseline, 67% of patients woke up OFF, with prevalence decreasing …

Fetal Fibronectin Testing For Reducing The Risk Of Preterm Birth., Vincenzo Berghella, Gabriele Saccone

Department of Obstetrics and Gynecology Faculty Papers

BACKGROUND: Fetal fibronectin (FFN) is an extracellular matrix glycoprotein localized at the maternal-fetal interface of the amniotic membranes, between chorion and decidua, where it is concentrated in this area between decidua and trophoblast. In normal conditions, FFN is found at very low levels in cervicovaginal secretions. Levels greater than or equal to 50 ng/mL at or after 22 weeks have been associated with an increased risk of spontaneous preterm birth. In fact, FFN is one of the best predictors of preterm birth in all populations studied so far, and can help in selecting which women are at significant risk for …

Report Of The First Patient Treated For Pelvic Sarcoma With A Directional 103pd Brachytherapy Device., Serguei A. Castaneda, Marian Khalili, Jacqueline Emrich, Veronica M Zoghbi, Michael S Weingarten, Mark J Rivard, Wilbur B Bowne, Jaganmohan Poli

Department of Radiation Oncology Faculty Papers

No abstract provided.

Do Employees From Less-Healthy Communities Use More Care And Cost More? Seeking To Establish A Business Case For Investment In Community Health., Russell K. Mcintire, Martha C. Romney, Greg Alonzo, Jill Hutt, Lauren Bartolome, Greg Wood, Gary Klein, Neil I. Goldfarb

College of Population Health Faculty Papers

INTRODUCTION: Few studies have examined the impact of community health on employers. We explored whether employed adults and their adult dependents living in less-healthy communities in the greater Philadelphia region used more care and incurred higher costs to employers than employees from healthier communities.

METHODS: We used a multi-employer database to identify adult employees and dependents with continuous employment and mapped them to 31 zip code regions. We calculated community health scores at the regional level, by using metrics similar to the Robert Wood Johnson Foundation (RWJF) County Health Rankings but with local data. We used descriptive analyses and multilevel …

Functionalization Of Cd36 Cardiovascular Disease And Expression Associated Variants By Interdisciplinary High Throughput Analysis., Namrata Madan, Andrew R. Ghazi, Xianguo Kong, Edward S. Chen, Chad A. Shaw, Leonard C. Edelstein

Department of Medicine Faculty Papers

CD36 is a platelet membrane glycoprotein whose engagement with oxidized low-density lipoprotein (oxLDL) results in platelet activation. The CD36 gene has been associated with platelet count, platelet volume, as well as lipid levels and CVD risk by genome-wide association studies. Platelet CD36 expression levels have been shown to be associated with both the platelet oxLDL response and an elevated risk of thrombo-embolism. Several genomic variants have been identified as associated with platelet CD36 levels, however none have been conclusively demonstrated to be causative. We screened 81 expression quantitative trait loci (eQTL) single nucleotide polymorphisms (SNPs) associated with platelet CD36 expression …

Cleavage And Sub-Cellular Redistribution Of Nuclear Pore Protein 98 By Coxsackievirus B3 Protease 2a Impairs Cardioprotection., Paul J. Hanson, Al Rohet Hossain, Ye Qiu, Huifang M. Zhang, Guangze Zhao, Cheng Li, Veena Lin, Saheedat Sulaimon, Marli Vlok, Gabriel Fung, Victoria H. Chen, Eric Jan, Bruce M. Mcmanus, David J. Granville, Decheng Yang

College of Population Health Faculty Papers

Myocarditis, inflammation of the heart muscle, affects all demographics and is a major cause of sudden and unexpected death in young people. It is most commonly caused by viral infections of the heart, with coxsackievirus B3 (CVB3) being among the most prevalent pathogens. To understand the molecular pathogenesis of CVB3 infection and provide strategies for developing treatments, we examined the role of a key nuclear pore protein 98 (NUP98) in the setting of viral myocarditis. NUP98 was cleaved as early as 2 h post-CVB3 infection. This cleavage was further verified through both the ectopic expression of viral proteases and in …

Assessment Of The Risk And Characterization Of Non-Melanoma Skin Cancer In Kindler Syndrome: Study Of A Series Of 91 Patients., Sara Guerrero-Aspizua, Claudio J. Conti, Maria Jose Escamez, Daniele Castiglia, Giovanna Zambruno, Leila Youssefian, Hassan Vahidnezhad, Luis Requena, Peter Itin, Gianluca Tadini, Ivelina Yordanova, Ludovic Martin, Jouni Uitto, Cristina Has, Marcela Del Rio

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND: Kindler Syndrome (KS) is a rare genodermatosis characterized by skin fragility, skin atrophy, premature aging and poikiloderma. It is caused by mutations in the FERMT1 gene, which encodes kindlin-1, a protein involved in integrin signalling and the formation of focal adhesions. Several reports have shown the presence of non-melanoma skin cancers in KS patients but a systematic study evaluating the risk of these tumors at different ages and their potential outcome has not yet been published. We have here addressed this condition in a retrospective study of 91 adult KS patients, characterizing frequency, metastatic potential and body distribution of …

Prognostic Significance Of Tumor-Associated Macrophage Content In Head And Neck Squamous Cell Carcinoma: A Meta-Analysis., Ayan Tyagi Kumar, Alexander Knops, Brian Swendseid, Md, Ubaldo E. Martinez-Outshoorn, Larry Harshyne, Nancy Philp, Ulrich Rodeck, Adam Luginbuhl, David Cognetti, Jennifer Johnson, Joseph Curry

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Background: Head and neck squamous cell carcinoma (HNSCC) exists within a microenvironment rich in immune cells. Macrophages are particularly abundant in and around tumor tissue, and have been implicated in the growth, malignancy, and persistence of HNSCC (1). However, current literature reports variable degrees of association between the density of tumor-associated macrophages (TAMs) and clinicopathologic markers of disease (2, 3). These inconsistent findings may be a result of differences in approach to TAM detection. Authors have measured total TAMs in tumor tissue, while others have stained tumor samples for individual subtypes of TAMs, which include pro-inflammatory (M1-like) and immunosuppressive (M2-like). …

Codelivery Of Genistein And Mirna-29b To A549 Cells Using Aptamer-Hybrid Nanoparticle Bioconjugates., Koita Sacko, Karthik Thangavel, Sunday A. Shoyele

College of Pharmacy Faculty Papers

This study aimed to evaluate the anti-cancer effect of a combination therapy of miRNA-29b and genistein loaded in mucin-1 (MUC 1)-aptamer functionalized hybrid nanoparticles in non-small cell lung cancer (NSCLC) A549 cell line. Genistein-miRNA-29b-loaded hybrid nanoparticles (GMLHN) was prepared and characterized. Particle size and zeta potential were measured using photon correlation spectroscopy (PCS). Encapsulation efficiency and loading efficiency were determined using HPLC. Preferential internalization of MUC 1-aptamer functionalized GMLHN by A549 cells was evaluated and compared to normal MRC-5 cells. The ability of GMLHN to downregulate targeted oncoproteins Phosphorylated protein kinase, strain AK, Thymoma (Phosphorylated protein kinase B) (pAKT), Phosphorylated …

The Bone Extracellular Matrix As An Ideal Milieu For Cancer Cell Metastases., Alexus D. Kolb, Karen M. Bussard

Department of Cancer Biology Faculty Papers

Bone is a preferential site for cancer metastases, including multiple myeloma, prostate, and breast cancers.The composition of bone, especially the extracellular matrix (ECM), make it an attractive site for cancer cell colonization and survival. The bone ECM is composed of living cells embedded within a matrix composed of both organic and inorganic components. Among the organic components, type I collagen provides the tensile strength of bone. Inorganic components, including hydroxyapatite crystals, are an integral component of bone and provide bone with its rigidity. Under normal circumstances, two of the main cell types in bone, the osteoblasts and osteoclasts, help to …

Mdivi-1, A Mitochondrial Fission Inhibitor, Modulates T Helper Cells And Suppresses The Development Of Experimental Autoimmune Encephalomyelitis., Yan-Hua Li, Fang Xu, Rodolfo Thome, Min-Fang Guo, Man-Luan Sun, Guo-Bin Song, Rui-Lan Li, Zhi Chai, Bogoljub Ciric, A. M. Rostami, Mark T. Curtis, Cun-Gen Ma, Guang-Xian Zhang

Department of Neurology Faculty Papers

BACKGROUND: Unrestrained activation of Th1 and Th17 cells is associated with the pathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). While inactivation of dynamin-related protein 1 (Drp1), a GTPase that regulates mitochondrial fission, can reduce EAE severity by protecting myelin from demyelination, its effect on immune responses in EAE has not yet been studied.

METHODS: We investigated the effect of Mdivi-1, a small molecule inhibitor of Drp1, on EAE. Clinical scores, inflammation, demyelination and Drp1 activation in the central nervous system (CNS), and T cell responses in both CNS and periphery were determined.

RESULTS: Mdivi-1 effectively …

Symmetrical Peripheral Gangrene Associated With Low Output Cardiac Failure., Sijan Basnet, Priya Rajagopalan, Rashmi Dhital, Ataul Qureshi

Department of Medicine Faculty Papers

Symmetrical peripheral gangrene (SPG) is a rare entity characterized by ischemic changes of the distal extremities with maintained vascular integrity. We present the case of a 64-year-old man with bilateral necrotic toes and deranged liver function tests. This was thought to be related to severely depressed ejection fraction from non-ischemic etiology, presumably chronic alcohol ingestion. We hope that awareness of SPG and association with a low output state will aid in early detection and prevention.

Adopting The Direct Anterior Approach: Experience And Learning Curve In A Chinese Patient Population., Xiangpeng Kong, Luis Grau, Alvin Ong, Charlie Yang, Wei Chai

Rothman Institute Papers

BACKGROUND: There are concerns regarding the complications encountered during the learning curve when switching to a direct anterior approach (DAA) for total hip arthroplasty (THA). The purpose of our study is to report our outcomes and complications after adopting a new approach in a Chinese patient population.

METHODS: From 2016 to 2018, a single surgeon's first 100 cases with unilateral DAA for THA were reviewed. The patients were divided into 2 groups, the first 50 cases were designated as group A and the second 50 cases were designated as group B. The preoperative, intraoperative, and postoperative clinical data were analyzed. …

Use Of Plasmapheresis And Immunosuppressants To Treat Diffuse Alveolar Hemorrhage In A Patient With Granulomatosis With Polyangiitis., Yasar Sattar, Ammu Thampi Susheela, Waqas Ullah, Norina Usman, Fnu Zafrullah

Abington Jefferson Health Papers

Granulomatosis with polyangiitis (GPA) is a systemic granulomatous inflammatory disease characterized by small-to-medium vessel vasculitis due to Central Anti-Neutrophil Cytoplasmic Antibody (C-ANCA). GPA commonly involves the lungs and the kidneys. Among the pulmonary manifestations, diffuse alveolar hemorrhage (DHA) is a rare presentation of GPA that can present with hemoptysis leading to acute onset of anemia and hemodynamic instability. An active diagnostic workup including serologic titer of C-ANCA, imaging, intensive care, and aggressive immunosuppression is the key to DAH management. We report a case of DAH secondary to GPA that presented with hemoptysis leading to severe anemia, initially resuscitated symptomatically and …

Bitter Taste Receptors For Asthma Therapeutics., Ajay P. Nayak, Sushrut D. Shah, James V. Michael, Deepak A. Deshpande

Center for Translational Medicine Faculty Papers

Clinical management of asthma and chronic obstructive pulmonary disease (COPD) has primarily relied on the use of beta 2 adrenergic receptor agonists (bronchodilators) and corticosteroids, and more recently, monoclonal antibody therapies (biologics) targeting specific cytokines and their functions. Although these approaches provide relief from exacerbations, questions remain on their long-term efficacy and safety. Furthermore, current therapeutics do not address progressive airway remodeling (AR), a key pathological feature of severe obstructive lung disease. Strikingly, agonists of the bitter taste receptors (TAS2Rs) deliver robust bronchodilation, curtail allergen-induced inflammatory responses in the airways and regulate airway smooth muscle (ASM) cell proliferation and mitigate …

Patient Registries In Idiopathic Pulmonary Fibrosis., Daniel A. Culver, Jürgen Behr, John A. Belperio, Tamera J. Corte, Joao A. De Andrade, Kevin R. Flaherty, Mridu Gulati, Tristan J. Huie, Lisa H. Lancaster, Jesse Roman, Christopher J. Ryerson, Hyun J. Kim

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

Over the past decade, several large registries of patients with idiopathic pulmonary fibrosis (IPF) have been established. These registries are collecting a wealth of longitudinal data on thousands of patients with this rare disease. The data collected in these registries will be complementary to data collected in clinical trials because the patient populations studied in registries have a broader spectrum of disease severity and comorbidities and can be followed for a longer period of time. Maintaining the quality and completeness of registry databases presents administrative and resourcing challenges, but it is important to ensuring the robustness of the analyses. Data …

Spg7 Targets The M-Aaa Protease Complex To Process Mcu For Uniporter Assembly, Ca2 Influx, And Regulation Of Mitochondrial Permeability Transition Pore Opening, Stephen Hurst, Ariele Baggett, György Csordás, Shey-Shing Sheu

Center for Translational Medicine Faculty Papers

The mitochondrial matrix ATPase associated with diverse cellular activities (m-AAA) protease spastic paraplegia 7 (SPG7) has been recently implicated as either a negative or positive regulatory component of the mitochondrial permeability transition pore (mPTP) by two research groups. To address this controversy, we investigated possible mechanisms that explain the discrepancies between these two studies. We found that loss of the SPG7 gene increased resistance to Ca²-induced mPTP opening. However, this occurs independently of cyclophilin D (cyclosporine A insensitive) rather it is through decreased mitochondrial Ca² concentrations and subsequent adaptations mediated by impaired formation of functional mitochondrial Ca …

From Vaccine Vector To Oncomodulation: Understanding The Complex Interplay Between Cmv And Cancer., Nicole A. Wilski, Christopher M. Snyder

Department of Microbiology and Immunology Faculty Papers

Cytomegalovirus (CMV) is a herpesvirus that establishes a persistent, but generally asymptomatic, infection in most people in the world. However, CMV drives and sustains extremely large numbers of antigen-specific T cells and is, therefore, emerging as an exciting platform for vaccines against infectious diseases and cancer. Indeed, pre-clinical data strongly suggest that CMV-based vaccines can sustain protective CD8+ T cell and antibody responses. In the context of vaccines for infectious diseases, substantial pre-clinical studies have elucidated the effcacy and protective mechanisms of CMV-based vaccines, including in non-human primate models of various infections. In the context of cancer vaccines, however, much …

Myc-Mediated Transcriptional Regulation Of The Mitochondrial Chaperone Trap1 Controls Primary And Metastatic Tumor Growth., Ekta Agarwal, Brian J. Altman, Jae Ho Seo, Jagadish C. Ghosh, Andrew V Kossenkov, Hsin-Yao Tang, Shiv Ram Krishn, Lucia R. Languino, Dmitry I. Gabrilovich, David W. Speicher, Chi V. Dang, Dario C. Altieri

Department of Cancer Biology Faculty Papers

The role of mitochondria in cancer continues to be debated, and whether exploitation of mitochondrial functions is a general hallmark of malignancy or a tumor- or context-specific response is still unknown. Using a variety of cancer cell lines and several technical approaches, including siRNA-mediated gene silencing, ChIP assays, global metabolomics and focused metabolite analyses, bioenergetics, and cell viability assays, we show that two oncogenic Myc proteins, c-Myc and N-Myc, transcriptionally control the expression of the mitochondrial chaperone TNFR-associated protein- 1 (TRAP1) in cancer. In turn, this Myc-mediated regulation preserved the folding and function of mitochondrial oxidative phosphorylation (OXPHOS) complex II …

Matrix Metalloproteinase Activity In The Lung Is Increased In Hermansky-Pudlak Syndrome., Ross Summer, Rachana Krishna, Deleila Schriner, Karina Cuevas-Mora, Dominic Sales, Rachel Para, Jesse Roman, Carl Nieweld, Bernadette R. Gochuico, Freddy Romero

Center for Translational Medicine Faculty Papers

BACKGROUND: Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder characterized by oculocutaneous albinism and platelet dysfunction and can sometimes lead to a highly aggressive form of pulmonary fibrosis that mimics the fatal lung condition called idiopathic pulmonary fibrosis (IPF). Although the activities of various matrix metalloproteinases (MMPs) are known to be dysregulated in IPF, it remains to be determined whether similar changes in these enzymes can be detected in HPS.

RESULTS: Here, we show that transcript and protein levels as well as enzymatic activities of MMP-2 and -9 are markedly increased in the lungs of mice carrying the HPS …