Respiratory Tract Diseases Commons^™

Ribosome Hibernation In Mycobacterium Abscessus And Its Effect On Antibiotic Resistance, Ryan Treen

Electronic Theses & Dissertations (2024 - present)

Non-tuberculosis mycobacteria (NTM) represent a diverse repertoire of species, most of which are ubiquitous in the environment. Some NTM species, such as Mycobacterium abscessus, can cause life-threatening infections in people with underlying medical conditions. The clinical incidence of such infections is on the rise, posing an emerging threat to public health. M. abscessus is characterized by intrinsic and acquired antibiotic resistance, complicating treatment strategies. Most chemotherapeutic approaches for M. abscessus infection target the bacterial ribosome, necessitating a better understanding of the physiological processes which confer this resistance. Multiple mycobacterial species respond to zinc-limiting conditions by inducing remodeling and hibernation …

Reducing Healthcare-Acquired Pneumonia In A Geriatric Long-Term Care Facility, Jacob R. Magsalin

Master's Projects and Capstones

Problem: Healthcare-acquired pneumonia (HAP) is a nosocomial infection that poses a serious threat in geriatric long-term care facilities due to its high morbidity and mortality.

Context: This evidence-based quality improvement project seeks to reduce the incidence of HAP in a geriatric long-term care facility in the San Francisco Bay Area by utilizing findings

from existing literature.

Interventions: Key interventions include improving and standardizing oral care techniques and promoting education on HAP prevention to allow patients and their families to be more proactive in preventing this complication.

Measures: Outcome measures include HAP diagnosis rates after implementation, any costs saved for the …

Reducing The Incidence Of Nosocomial Aspiration Pneumonia In The Adult Oncology Population Through Improved Compliance With Oral Hygiene Protocols, Kenneth R. Brown

Master's Projects and Capstones

Objective

Oncology patients receiving chemotherapy are at risk of complications such as mucosal barrier injuries (MBI) and aspiration pneumonia, and aspiration pneumonia rates are higher than desired. Improved oral hygiene protocols and compliance in this population reduces the incidence of these complications.

Context and Background

The microsystem assessed includes six oncology units at Hospital A, a large California academic hospital. Aspiration pneumonia, commonly associated with MBI, is a life-threatening challenge that increases costs and complications in oncological treatment settings. An aspiration pneumonia task force focused on six oncology acute care units is committed to reducing the incidence of hospital acquired …

Obstructive Sleep Apnea And Obesity: How Weight Loss Improves Sleep Apnea Severity And Quality Of Life - An Integrative Review, Hannah Wilson, Neda Akbarshahi

Master's Projects

Introduction: With the growing prevalence of OSA due to the obesity epidemic, there is an urgent need to update treatment regimens. While CPAP continues to be the gold standard of OSA care, challenges with adherence and limited access to effective weight management strategies often impede care. The complex bidirectional relationship between obesity and OSA highlights the importance of addressing weight management in this patient population to help mitigate cardiometabolic risks. Personalized weight loss therapies should be integrated into standard OSA treatment regimens to reduce OSA severity, reduce comorbid conditions, and improve quality of life.

Aim: The objective of this integrative …

Use Of Empagliflozin As An Adjuvant Treatment For Obstructive Sleep Apnea For A Patient Who Has Not Seen A Physician In Over 40 Years, Andrew Demko

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Neeland IJ, Eliasson B, Kasai T, et al. The Impact of Empagliflozin on Obstructive Sleep Apnea and Cardiovascular and Renal Outcomes: An Exploratory Analysis of the EMPA-REG OUTCOME Trial. Diabetes Care. 2020;43(12):3007-3015. https://doi.org/10.2337/dc20-1096

for a patient with obstructive sleep apnea who has not seen a physician in over 40 years.

Association Between Various Types Of Corticosteroids And Mortality For Severe Community-Acquired Pneumonia In Adults: A Systematic Review And Network Meta-Analysis, Peng Wang, Jun Wan, Qiaoyu You, Yuxin Zheng, Wenhao Xu, Jialing He, Liyuan Peng, Cuyubamba Dominguez Jorge Luis, Yuning Feng, Ping Xu, Xinrong Li, Weelic Chong, Yang Hai, Lu Jia, Fang Fang, Yu Zhang

Department of Medical Oncology Faculty Papers

OBJECTIVE: This study aims to conduct a systematic review and network meta-analysis to evaluate the efficacy and safety of specific corticosteroids, including but not limited to hydrocortisone, methylprednisolone, prednisolone, and dexamethasone, in the treatment of severe community-acquired pneumonia (SCAP). Efficacy will be assessed using specific outcomes, such as 30-day mortality and the requirement for mechanical ventilation. Safety evaluations will include adverse events like gastrointestinal bleeding and healthcare-associated infections. The study seeks to address the gaps identified in the latest guidelines regarding the optimal use of different corticosteroid types and to provide recommendations for clinical practice.

DATA SOURCES: This study conducted …

Cardiopulmonary Exercise Testing In Pulmonary Arterial Hypertension And Chronic Thromboembolic Pulmonary Hypertension, Alexis Coulis, Shir Levanon, Gurshaun Randhawa, Yevgeniy Brailovsky, Farhan Raza, Estefania Oliveros

Division of Cardiology Faculty Papers

Cardiopulmonary exercise testing allows for a comprehensive assessment of the mechanism of exercise limitation in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Competitive pathophysiologic mechanisms may affect the clinical interpretation of cardiopulmonary disease as they relate to dyspnea, leg fatigue, and exercise intolerance.

Management Of Covid-19 In A Patient With Kartagener Syndrome: A Case Report, Yatin Ramesh Babu, Shivani Patel, Andy Aleman Espino, Mallory Kazaleh, Hamlet Monteagudo, Odalys Frontela

HCA-NSU MD Research Day

The unprecedented global health challenge posed by COVID-19, caused by SARS-CoV-2, has driven research into its diverse clinical manifestations and underlying pathophysiological mechanisms. This report explores the interplay between pre-existing conditions, particularly Kartagener Syndrome, and COVID-19 outcomes. Kartagener Syndrome, characterized by primary ciliary dyskinesia, presents a unique perspective due to its anatomical and physiological features. The case details a 63-year-old female with Kartagener Syndrome admitted with COVID-19 symptoms. The gold-standard approach for Kartagener Syndrome involves comprehensive management strategies, including airway clearance techniques, pharmacotherapy, and surgical interventions. The patient's treatment encompassed bronchodilators, antibiotics, and subsequent improvements, leading to discharge with a …

To Be Or Not Tb, Gerald Chang, Leidy Huie Martinez Md, Carlos Correa Md, Jose Melendez Md, Brittany Puebla Ms, Yeissen Godinez Md

HCA-NSU MD Research Day

Introduction: Tuberculosis (TB) is an aerosol-transmitted disease that primarily affects the lungs, with active infection presenting as fever, night sweats, weight loss, and productive cough. While it is prevalent worldwide, there may be a lower degree of clinical suspicion in developed countries where it remains uncommon. Therefore, it is important to focus on certain risk factors (travel history, immunosuppression, certain living conditions) in the patient workup. The purpose of this case report is to discuss the presentation and management of a patient with active TB presenting atypically. Case Description: The 47yo male patient with a recent history of pneumonia presented …

The Complex Relationship Between Tuberculosis And Hyperglycemia, Michelle Byers, Elizabeth Guy

Faculty, Staff and Students Publications

Hyperglycemia and tuberculosis are dual global pandemics. Each has a propulsive and amplifying effect on the other, and, because of this, we must consider hyperglycemia and tuberculosis together. Hyperglycemia is immunosuppressive and increases the risk of tuberculosis by threefold. It also leads to a more advanced presentation of pulmonary tuberculosis, thus increasing the likelihood of being smear positive and having cavitating lesions, and it impacts the duration and outcomes of treatment, with an increased one year mortality seen in patients with tuberculosis and diabetes. Additionally, any degree of hyperglycemia can have an impact on susceptibility to tuberculosis, and this effect …

Best Practice Toolkit For Nursing Staff Caring For Ventilated Patients, Erin Belisle

Student Scholarly Projects

Practice Problem: Best practice tool kits are used to guide better outcomes for ventilated patients and staff members. Many reasons can contribute to requiring a patient to be on mechanical ventilation, but the most common reasons are a trauma event and infection.

PICOT: The PICOT question that guided this project was: In critical care staff such as nurses, respiratory therapists (RT), and critical care providers caring for mechanically ventilated patients (P), what is the effect of implementing a best practice coordination toolkit (I) compared to standard care procedures (C) on the adherence to best practices by critical care providers (O)? …

Characteristics Of Exacerbators In The Us Bronchiectasis And Ntm Research Registry: A Cross-Sectional Study, Nicole C. Lapinel, Radmila Choate, Timothy R. Aksamit, Joseph Feliciano, Kevin L. Winthrop, Andreas Schmid, Sebastian Fucile, Mark L. Metersky

School of Medicine Faculty Publications

BACKGROUND: Exacerbations of noncystic fibrosis bronchiectasis (bronchiectasis) are associated with reduced health-related quality of life and increased mortality, likelihood of hospitalisation and lung function decline. This study investigated patient clinical characteristics associated with exacerbation frequency. METHODS: A cross-sectional cohort study of patients ≥ 18 years with bronchiectasis enrolled in the US Bronchiectasis and Nontuberculous Mycobacteria (NTM) Research Registry (BRR) September 2008-March 2020. Patients were stratified by exacerbation frequency in their 2 years before enrolment. Patient demographics, respiratory symptoms, healthcare resource utilisation, microbiology, modified bronchiectasis severity index (mBSI) and select comorbidities were collected at enrolment. Patient characteristics associated with exacerbation frequency …

Current Understanding Of The Impact Of United States Military Airborne Hazards And Burn Pit Exposures On Respiratory Health, Janeen Trembley, Paul Barach, Julie Tomáška, Jedidah Poole, Pamela Ginex, Robert Miller, Jacob Lindheimer, Anthony Szema, Kimberly Gandy, Trishul Siddharthan, Jason Kirkness, Joshua Nixon, Rosie Lopez Torres, Mark Klein, Timothy Nurkiewicz, Tammy Butterick

College of Population Health Faculty Papers

Millions of United States (U.S.) troops deployed to the Middle East and Southwest Asia were exposed to toxic airborne hazards and/or open-air burn pits. Burn pit emissions contain particulate matter combined with toxic gasses and heavy metals. Ongoing research has demonstrated that exposures to the airborne hazards from military burn pits have profound and lasting health and wellness consequences. Research on the long-term health consequences of exposure to open burn pits has been limited. Work continues to understand the scope of the health impacts and the underlying pathobiology following exposures and to establish care standards. The U.S. Sergeant First Class …

Α4 Nicotinic Acetylcholine Receptors In Lipopolysaccharide-Related Lung Inflammation, J. Ritzenthaler, Walter H. Watson, Jesse Roman

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

Sepsis remains an important healthcare challenge. The lungs are often affected in sepsis, resulting in acute lung injury characterized by inflammation. Mechanisms involving lipopolysaccharide (LPS) stimulation of toll-like receptor (TLR) signaling with induction of proinflammatory pathways have been implicated in this process. To date, however, studies targeting these pathways have failed to improve outcomes. We have found that LPS may also promote lung injury through the activation of α4 nicotinic acetylcholine receptors (α4 nAChRs) in immune cells. We observed increased expression of α4 nAChRs in human THP-1 monocytic cells exposed to LPS (100 ng/mL, 24 h). We also observed that …

Physician Perspectives About The Diagnosis And Management Of Acute Chest Syndrome, Neha Bhasin, Dana Marie Leblanc, Sean Yates, Quentin Eichbaum, An Pham, Deva Sharma, Li Zhang, Elliott P. Vichinsky, Ravi Sarode

School of Medicine Faculty Publications

Background: Acute chest syndrome (ACS) is the leading cause of mortality, accounting for 25% of all deaths among individuals with sickle cell disease (SCD). There is a lack of evidence-based laboratory and clinical risk stratification guidelines for the diagnosis and management of ACS. Study Design and Methods: To better understand physician practices for the management of ACS in the United States, we created an ACS Working Group including hematology and transfusion medicine physicians from four different SCD treatment centers in the United States. The working group created a physician survey that included physician demographics and ACS diagnostic criteria that they …

Multiregional Transcriptomic Profiling Provides Improved Prognostic Insight In Localized Non-Small Cell Lung Cancer, Chenyang Li, Thinh T Nguyen, Jian-Rong Li, Xingzhi Song, Junya Fujimoto, Latasha Little, Curtis Gumb, Chi-Wan B Chow, Ignacio I Wistuba, Andrew P Futreal, Jianhua Zhang, Shawna M Hubert, John V Heymach, Jia Wu, Christopher I Amos, Jianjun Zhang, Chao Cheng

Faculty, Staff and Student Publications

Lung Cancer remains the leading cause of cancer deaths in the USA and worldwide. Non-small cell lung cancer (NSCLC) harbors high transcriptomic intratumor heterogeneity (RNA-ITH) that limits the reproducibility of expression-based prognostic models. In this study, we used multiregional RNA-seq data (880 tumor samples from 350 individuals) from both public (TRACERx) and internal (MDAMPLC) cohorts to investigate the effect of RNA-ITH on prognosis in localized NSCLC at the gene, signature, and tumor microenvironment levels. At the gene level, the maximal expression of hazardous genes (expression negatively associated with survival) but the minimal expression of protective genes (expression positively associated with …

Multi-Ancestry Gwas Meta-Analyses Of Lung Cancer Reveal Susceptibility Loci And Elucidate Smoking-Independent Genetic Risk, Bryan R Gorman, Sun-Gou Ji, Michael Francis, Anoop K Sendamarai, Yunling Shi, Poornima Devineni, Uma Saxena, Elizabeth Partan, Andrea K Devito, Jinyoung Byun, Younghun Han, Xiangjun Xiao, Don D Sin, Wim Timens, Jennifer Moser, Sumitra Muralidhar, Rachel Ramoni, Rayjean J Hung, James D Mckay, Yohan Bossé, Ryan Sun, Christopher I Amos, Va Million Veteran Program, Saiju Pyarajan

Faculty, Staff and Student Publications

Lung cancer remains the leading cause of cancer mortality, despite declining smoking rates. Previous lung cancer GWAS have identified numerous loci, but separating the genetic risks of lung cancer and smoking behavioral susceptibility remains challenging. Here, we perform multi-ancestry GWAS meta-analyses of lung cancer using the Million Veteran Program cohort (approximately 95% male cases) and a previous study of European-ancestry individuals, jointly comprising 42,102 cases and 181,270 controls, followed by replication in an independent cohort of 19,404 cases and 17,378 controls. We then carry out conditional meta-analyses on cigarettes per day and identify two novel, replicated loci, including the 19p13.11 …

Forecasting The Effects Of Smoking Prevalence Scenarios On Years Of Life Lost And Life Expectancy From 2022 To 2050: A Systematic Analysis For The Global Burden Of Disease Study 2021, Gbd 2021 Tobacco Forecasting Collaborators

Ateneo School of Government Publications

Background

Smoking is the leading behavioural risk factor for mortality globally, accounting for more than 175 million deaths and nearly 4·30 billion years of life lost (YLLs) from 1990 to 2021. The pace of decline in smoking prevalence has slowed in recent years for many countries, and although strategies have recently been proposed to achieve tobacco-free generations, none have been implemented to date. Assessing what could happen if current trends in smoking prevalence persist, and what could happen if additional smoking prevalence reductions occur, is important for communicating the effect of potential smoking policies.

Methods

In this analysis, we use …

Effects Of Educational Intervention On Asthmatic Children, Zoe Coggins

Nursing | Student Research Posters

Abstract

Children are more vulnerable to asthmatic symptoms due to the physiological immaturity of their respiratory systems. Therefore, irritants are deemed more hazardous for the pediatric population. Pollution is a growing health concern, and within the literature review, several approaches to the measurement of the impact of low air quality and educational interventions are discussed. The themes identified in the literature review are increased risk of pollution-induced exacerbation due to age, behavior, and residential proximity to emission-producing facilities. The review of the literature demonstrated how pollution is a growing public health concern, especially among the pediatric population. Interventions, reviewed in …

Peran Pemeriksaan Penanda Tumor Cairan Pleura Dalam Diagnosis Efusi Pleura Maligna Akibat Kanker Paru Primer, Cleopas M. Rumende, Noorwati Sutandyo, Arif R. Hanafi, Samuel K. Rumende, Erwin C. Susanto, Truely P. Sitorus

Jurnal Penyakit Dalam Indonesia

Introduction. Pleural effusion is a frequently acquired lung disorder and based on the type of cause it is divided into malignant and non-malignant pleural effusion. Cytological examination of pleural fluid to differentiate between malignant and non-malignant pleural effusion shows varying sensitivity. Research regarding the benefits of CEA and Cyfra 21-1 pleural fluid examination to detect malignant pleural effusion due to primary lung cancer in Indonesia is still very limited. The aims of this study is to determine the sensitivity and specificity of CEA and Cyfra 21-1 pleural fluid in diagnosing malignant pleural effusion due to primary lung camcer.

Methods …

Ventilasi Noninvasif Pada Obstructive Sleep Apnea Dan Obesity Hypoventilation Syndrome, Herikurniawan Herikurniawan, Joanna Audrey, Firina Adelya

Jurnal Penyakit Dalam Indonesia

Chronic respiratory disease such as obstructive sleep apnea (OSA) and obesity-hypoventilation syndrome (OHS) remain are respiratory sleeping disorder that gradually affect quality of life. Comprehensive treatment such as the use of non-invasive ventilation (NIV) is a method adopted to improve the patient’s quality of life. The correct choice of NIV mode, mask and titration methods will provide optimal therapeutic effects to the patient. This article review lays out an update on the use of non-invasive ventilation as the treatment of OSA and OHS.

Pulmonary Fibrosis As A Presentation Of Short Telomere Syndrome: Case Report, Roy Kondapavuluru, Jian Garcia Cruz, Sreejith Pillai, Andres Suarez Parraga

Research Colloquium

Introduction: Short telomere syndrome (STS), also known as accelerated aging syndrome, is an inheritable gene mutation resulting in decreased telomere length causing high cell turnover of organ systems such as skin, bone marrow, liver, hair, lungs, and immune system. Due to diverse clinical manifestations, STS poses a diagnostic challenge, with bone marrow failure and idiopathic pulmonary fibrosis being frequent manifestations. The inherited form of STS demonstrates genetic anticipation occurring at an earlier age with more severe manifestations in the affected progeny. We present a rare case of inherited STS in a young patient with severe pulmonary fibrosis.

Case Presentation: A …

Immunoactive Signatures Of Circulating Trna- And Rrna-Derived Rnas In Chronic Obstructive Pulmonary Disease, Megumi Shigematsu, Takuya Kawamura, Deepak Deshpande, Yohei Kirino

Computational Medicine Center Faculty Papers

Chronic obstructive pulmonary disease (COPD) is the most prevalent lung disease, and macrophages play a central role in the inflammatory response in COPD. We here report a comprehensive characterization of circulating short non-coding RNAs (sncRNAs) in plasma from patients with COPD. While circulating sncRNAs are increasingly recognized for their regulatory roles and biomarker potential in various diseases, the conventional RNA sequencing (RNA-seq) method cannot fully capture these circulating sncRNAs due to their heterogeneous terminal structures. By pre-treating the plasma RNAs with T4 polynucleotide kinase, which converts all RNAs to those with RNA-seq susceptible ends (5′-phosphate and 3′-hydroxyl), we comprehensively sequenced …

Pleural Effusions In Patients Diagnosed With Pneumonia In Urgent Care Clinics, Nathan C. Dean, Jacqueline R. Eve, Allison M. Butler, James H. Hart, Theadora Sakata, Karen E. Connor, Edward A. Stenehjem, Y.C.G. Lee

The University of Louisville Journal of Respiratory Infections

Introduction: Pleural effusions in patients with community-acquired pneumonia have been associated with worse outcomes in emergency department and hospital inpatient populations, but the incidence of effusions and their outcomes in outpatient urgent care clinics is unknown. This observational cohort study describes patients diagnosed with pneumonia and pleural effusions on upright 2-view chest X-rays performed in urgent care clinics.

Methods: We extracted electronic health record data from January 2019 through December 2020 on all patients over 12 years old with an International Statistical Classification of Diseases 10^th revision diagnosis of pneumonia entered by the treating clinician, plus “possible” or “likely” …

Premalignant Progression In The Lung: Knowledge Gaps And Novel Opportunities For Interception Of Non-Small Cell Lung Cancer An Official American Thoracic Society Research Statement, Seyed Javad Moghaddam, Rajkumar Savai, Ramin Salehi-Rad, Shreoshi Sengupta, Michael N Kammer, Pierre Massion, Jennifer E Beane, Edwin J Ostrin, Carmen Priolo, Meredith A Tennis, Laura P Stabile, Alison K Bauer, Catherine R Sears, Eva Szabo, M Patricia Rivera, Charles A Powell, Humam Kadara, Brendan J Jenkins, Steven M Dubinett, A Mcgarry Houghton, Carla F Kim, Robert L Keith

Faculty, Staff and Student Publications

Rationale: Despite significant advances in precision treatments and immunotherapy, lung cancer is the most common cause of cancer death worldwide. To reduce incidence and improve survival rates, a deeper understanding of lung premalignancy and the multistep process of tumorigenesis is essential, allowing timely and effective intervention before cancer development. Objectives: To summarize existing information, identify knowledge gaps, formulate research questions, prioritize potential research topics, and propose strategies for future investigations into the premalignant progression in the lung. Methods: An international multidisciplinary team of basic, translational, and clinical scientists reviewed available data to develop and refine research questions pertaining to the …

Association Of Self-Reported Disease Severity With Depression And Anxiety Among Copd Patients, Yousef Saad Aldabayan, Antonieto Alaban, Eduardo Fabella, Amal Ismael Abdelhameed

Makara Journal of Health Research

Background: This study was conducted to estimate the proportion of patients who experience a high impact from chronic obstructive pulmonary disease (COPD) on their health status and those who also experience symptoms of depression and anxiety. It also sought to determine whether the health impact of the disease is associated with anxiety and depression.

Methods: An analytical cross-sectional study was conducted among 177 randomly selected patients with COPD seeking treatment in various primary health centers in Al Ahsa, Saudi Arabia. The COPD Assessment Test (CAT) was used to determine the impact of COPD on health generally, and the …

Inhibition Of Ulk1/2 And Kras G12c Controls Tumor Growth In Preclinical Models Of Lung Cancer, Phaedra C Ghazi, Kayla T O'Toole, Sanjana Srinivas Boggaram, Michael T Scherzer, Mark R Silvis, Yun Zhang, Madhumita Bogdan, Bryan D Smith, Guillermina Lozano, Daniel L Flynn, Eric L Snyder, Conan G Kinsey, Martin Mcmahon

Faculty, Staff and Student Publications

Mutational activation of KRAS occurs commonly in lung carcinogenesis and, with the recent U.S. Food and Drug Administration approval of covalent inhibitors of KRASG12C such as sotorasib or adagrasib, KRAS oncoproteins are important pharmacological targets in non-small cell lung cancer (NSCLC). However, not all KRASG12C-driven NSCLCs respond to these inhibitors, and the emergence of drug resistance in those patients who do respond can be rapid and pleiotropic. Hence, based on a backbone of covalent inhibition of KRASG12C, efforts are underway to develop effective combination therapies. Here, we report that the inhibition of KRASG12C signaling increases autophagy in KRASG12C-expressing lung cancer …

Asthma And Hyperglycemia: Exploring The Interconnected Pathways, Dharani K Narendra, Sandhya Khurana

Faculty, Staff and Students Publications

The interplay between asthma and glucose metabolism disorders, such as hyperglycemia, has gained increasing attention due to the potential exacerbation of asthma symptoms and severity. This review explores the complex relationship between hyperglycemia and asthma, emphasizing the pathophysiological links, the impact of glucose metabolism disorders on asthma, and the effects of asthma medications on glucose levels. Hyperglycemia, often induced by asthma treatments like corticosteroids, has been associated with an increased risk of asthma exacerbations. This review delves into the pathophysiology underlying this association, highlighting the role of insulin resistance, metabolic syndrome, and obesity in both the development and management of …

Lung Cell Transplantation For Pulmonary Fibrosis, Irit Milman Krentsis, Yangxi Zheng, Chava Rosen, Sarah Y Shin, Christa Blagdon, Einav Shoshan, Yuan Qi, Jing Wang, Sandeep K Yadav, Esther Bachar Lustig, Elias Shetzen, Burton F Dickey, Harry Karmouty-Quintana, Yair Reisner

Faculty, Staff and Student Publications

Idiopathic pulmonary fibrosis is a major cause of death with few treatment options. Here, we demonstrate the therapeutic efficacy for lung fibrosis of adult lung cell transplantation using a single-cell suspension of the entire lung in two distinct mouse systems: bleomycin treatment and mice lacking telomeric repeat-binding factor 1 expression in alveolar type 2 (AT2) cells (SPC-Cre TRF1fl/fl), spontaneously developing fibrosis. In both models, the progression of fibrosis was associated with reduced levels of host lung progenitors, enabling engraftment of donor progenitors without any additional conditioning, in contrast to our previous studies. Two months after transplantation, engrafted progenitors …

G12/13 Signaling In Asthma, Elizabeth L. Mcduffie, Reynold A Panettieri, Charles P. Scott

Department of Biochemistry and Molecular Biology Faculty Papers

Shortening of airway smooth muscle and bronchoconstriction are pathognomonic for asthma. Airway shortening occurs through calcium-dependent activation of myosin light chain kinase, and RhoA-dependent calcium sensitization, which inhibits myosin light chain phosphatase. The mechanism through which pro-contractile stimuli activate calcium sensitization is poorly understood. Our review of the literature suggests that pro-contractile G protein coupled receptors likely signal through G12/13 to activate RhoA and mediate calcium sensitization. This hypothesis is consistent with the effects of pro-contractile agonists on RhoA and Rho kinase activation, actin polymerization and myosin light chain phosphorylation. Recognizing the likely role of G12/13 signaling in the pathophysiology …