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Evolution Of The Alpha-1 Antitrypsin Muscle Gene Therapy: Translation From Clinical Trial To Benchtop And Back Again, Alisha M. Gruntman, Gwladys Gernoux, Gensheng Wang, Janet Benson, Jeff Chulay, Dave Knop, Christian Mueller, Terence R. Flotte 2017 University of Massachusetts Medical School

Evolution Of The Alpha-1 Antitrypsin Muscle Gene Therapy: Translation From Clinical Trial To Benchtop And Back Again, Alisha M. Gruntman, Gwladys Gernoux, Gensheng Wang, Janet Benson, Jeff Chulay, Dave Knop, Christian Mueller, Terence R. Flotte

Christian Mueller

Alpha-one antitrypsin (AAT) deficiency is a genetic disease affecting the lungs due to inadequate anti-protease activity in the pulmonary interstitium. On-going human trials use intra-muscular delivery of adeno-associated virus (rAAV1), allowing expressing myofibers to secrete normal (M)AAT protein. In the Phase IIa trial, patients in the highest dose cohort (6x1012vg/kg) were given 100 intra-muscular (IM) injections of undiluted vector, with serum AAT levels still substantially below target levels. Previous work has shown that delivering rAAV vector to the musculature via limb perfusion leads to widespread gene expression in myofibers. We hypothesize that widespread delivery would result in an ...


Lung Ultrasound As A Diagnostic Tool For Radiographically-Confirmed Pneumonia In Low Resource Settings, L E. Ellington, R H. Gilman, M A. Chavez, F Pervaiz, J Marin-Concha, P Compen-Chang, S Riedel, S J. Rodriguez, C Gaydos, J Hardick, J M. Tielsch, M Steinhoff, J Benson, E A. May, D Figueroa-Quintanilla, W Checkley 2017 George Washington University

Lung Ultrasound As A Diagnostic Tool For Radiographically-Confirmed Pneumonia In Low Resource Settings, L E. Ellington, R H. Gilman, M A. Chavez, F Pervaiz, J Marin-Concha, P Compen-Chang, S Riedel, S J. Rodriguez, C Gaydos, J Hardick, J M. Tielsch, M Steinhoff, J Benson, E A. May, D Figueroa-Quintanilla, W Checkley

Global Health Faculty Publications

Background

Pneumonia is a leading cause of morbidity and mortality in children worldwide; however, its diagnosis can be challenging, especially in settings where skilled clinicians or standard imaging are unavailable. We sought to determine the diagnostic accuracy of lung ultrasound when compared to radiographically-confirmed clinical pediatric pneumonia.

Methods

Between January 2012 and September 2013, we consecutively enrolled children aged 2–59 months with primary respiratory complaints at the outpatient clinics, emergency department, and inpatient wards of the Instituto Nacional de Salud del Niño in Lima, Peru. All participants underwent clinical evaluation by a pediatrician and lung ultrasonography by one of ...


Impact Of Neuraminidase Inhibitors On Influenza A(H1n1)Pdm09-Related Pneumonia: An Individual Participant Data Meta-Analysis, Stella G Muthuri, Sudhir Venkatesan, Puja R Myles, Jo Leonardi-Bee, Wei Shen Lim, Abdullah Al Mamun, Ashish P Anovadiya, Wildo N Araújo, Eduardo Azziz-Baumgartner, Clarisa Báez, Carlos Bantar, Mazen M Barhoush, Matteo Bassetti, Bojana Beovic, Roland Bingisser, Isabelle Bonmarin, Victor H Borja-Aburto, Bin Cao, Jordi Carratala, María R Cuezzo, Justin T Denholm, Samuel R Dominguez, Pericles A D Duarte, Gal Dubnov-Raz, Marcela Echavarria, Sergio Fanella, James Fraser, Zhancheng Gao, Patrick Gérardin, Maddalena Giannella, Sophie Gubbels, Jethro Herberg, Anjarath L Higuera Iglesias, Peter H Hoeger, Matthias Hoffmann, Xiaoyun Hu, Quazi T Islam, Mirela F Jiménez, Amr Kandeel, Gerben Keijzers, Hossein Khalili, Gulam Khandaker, Marian Knight, Gabriela Kusznierz, Ilija Kuzman, Arthur M C Kwan, Idriss Lahlou Amine, Eduard Langenegger, Kamran B Lankarani, Yee-Sin Leo, Rita Linko, Pei Liu, Faris Madanat, Toshie Manabe, Elga Mayo-Montero, Allison McGeer, Ziad A Memish, Gokhan Metan, Dragan Mikić, Kristin G I Mohn, Ahmadreza Moradi, Pagbajabyn Nymadawa, Bulent Ozbay, Mehpare Ozkan, Dhruv Parekh, Mical Paul, Wolfgang Poeppl, Fernando P Polack, Barbara A Rath, Alejandro H Rodríguez, Marilda M Siqueira, Joanna Skręt-Magierło, Ewa Talarek, Julian W Tang, Antoni Torres, Selda H Törün, Dat Tran, Timothy M Uyeki, Annelies van Zwol, Wendy Vaudry, Daiva Velyvyte, Tjasa Vidmar, Paul Zarogoulidis, Jonathan S Nguyen-Van-Tam 2017 The University of Nottingham

Impact Of Neuraminidase Inhibitors On Influenza A(H1n1)Pdm09-Related Pneumonia: An Individual Participant Data Meta-Analysis, Stella G Muthuri, Sudhir Venkatesan, Puja R Myles, Jo Leonardi-Bee, Wei Shen Lim, Abdullah Al Mamun, Ashish P Anovadiya, Wildo N Araújo, Eduardo Azziz-Baumgartner, Clarisa Báez, Carlos Bantar, Mazen M Barhoush, Matteo Bassetti, Bojana Beovic, Roland Bingisser, Isabelle Bonmarin, Victor H Borja-Aburto, Bin Cao, Jordi Carratala, María R Cuezzo, Justin T Denholm, Samuel R Dominguez, Pericles A D Duarte, Gal Dubnov-Raz, Marcela Echavarria, Sergio Fanella, James Fraser, Zhancheng Gao, Patrick Gérardin, Maddalena Giannella, Sophie Gubbels, Jethro Herberg, Anjarath L Higuera Iglesias, Peter H Hoeger, Matthias Hoffmann, Xiaoyun Hu, Quazi T Islam, Mirela F Jiménez, Amr Kandeel, Gerben Keijzers, Hossein Khalili, Gulam Khandaker, Marian Knight, Gabriela Kusznierz, Ilija Kuzman, Arthur M C Kwan, Idriss Lahlou Amine, Eduard Langenegger, Kamran B Lankarani, Yee-Sin Leo, Rita Linko, Pei Liu, Faris Madanat, Toshie Manabe, Elga Mayo-Montero, Allison Mcgeer, Ziad A Memish, Gokhan Metan, Dragan Mikić, Kristin G I Mohn, Ahmadreza Moradi, Pagbajabyn Nymadawa, Bulent Ozbay, Mehpare Ozkan, Dhruv Parekh, Mical Paul, Wolfgang Poeppl, Fernando P Polack, Barbara A Rath, Alejandro H Rodríguez, Marilda M Siqueira, Joanna Skręt-Magierło, Ewa Talarek, Julian W Tang, Antoni Torres, Selda H Törün, Dat Tran, Timothy M Uyeki, Annelies Van Zwol, Wendy Vaudry, Daiva Velyvyte, Tjasa Vidmar, Paul Zarogoulidis, Jonathan S Nguyen-Van-Tam

Gerben Keijzers

BACKGROUND:

The impact of neuraminidase inhibitors (NAIs) on influenza-related pneumonia (IRP) is not established. Our objective was to investigate the association between NAI treatment and IRP incidence and outcomes in patients hospitalised with A(H1N1)pdm09 virus infection.

METHODS:

A worldwide meta-analysis of individual participant data from 20 634 hospitalised patients with laboratory-confirmed A(H1N1)pdm09 (n = 20 021) or clinically diagnosed (n = 613) 'pandemic influenza'. The primary outcome was radiologically confirmed IRP. Odds ratios (OR) were estimated using generalised linear mixed modelling, adjusting for NAI treatment propensity, antibiotics and corticosteroids.

RESULTS:

Of 20 634 included participants, 5978 (29·0 ...


Impact Of Neuraminidase Inhibitors On Influenza A(H1n1)Pdm09-Related Pneumonia: An Individual Participant Data Meta-Analysis, Stella G Muthuri, Sudhir Venkatesan, Puja R Myles, Jo Leonardi-Bee, Wei Shen Lim, Abdullah Al Mamun, Ashish P Anovadiya, Wildo N Araújo, Eduardo Azziz-Baumgartner, Clarisa Báez, Carlos Bantar, Mazen M Barhoush, Matteo Bassetti, Bojana Beovic, Roland Bingisser, Isabelle Bonmarin, Victor H Borja-Aburto, Bin Cao, Jordi Carratala, María R Cuezzo, Justin T Denholm, Samuel R Dominguez, Pericles A D Duarte, Gal Dubnov-Raz, Marcela Echavarria, Sergio Fanella, James Fraser, Zhancheng Gao, Patrick Gérardin, Maddalena Giannella, Sophie Gubbels, Jethro Herberg, Anjarath L Higuera Iglesias, Peter H Hoeger, Matthias Hoffmann, Xiaoyun Hu, Quazi T Islam, Mirela F Jiménez, Amr Kandeel, Gerben Keijzers, Hossein Khalili, Gulam Khandaker, Marian Knight, Gabriela Kusznierz, Ilija Kuzman, Arthur M C Kwan, Idriss Lahlou Amine, Eduard Langenegger, Kamran B Lankarani, Yee-Sin Leo, Rita Linko, Pei Liu, Faris Madanat, Toshie Manabe, Elga Mayo-Montero, Allison McGeer, Ziad A Memish, Gokhan Metan, Dragan Mikić, Kristin G I Mohn, Ahmadreza Moradi, Pagbajabyn Nymadawa, Bulent Ozbay, Mehpare Ozkan, Dhruv Parekh, Mical Paul, Wolfgang Poeppl, Fernando P Polack, Barbara A Rath, Alejandro H Rodríguez, Marilda M Siqueira, Joanna Skręt-Magierło, Ewa Talarek, Julian W Tang, Antoni Torres, Selda H Törün, Dat Tran, Timothy M Uyeki, Annelies van Zwol, Wendy Vaudry, Daiva Velyvyte, Tjasa Vidmar, Paul Zarogoulidis, Jonathan S Nguyen-Van-Tam 2017 The University of Nottingham

Impact Of Neuraminidase Inhibitors On Influenza A(H1n1)Pdm09-Related Pneumonia: An Individual Participant Data Meta-Analysis, Stella G Muthuri, Sudhir Venkatesan, Puja R Myles, Jo Leonardi-Bee, Wei Shen Lim, Abdullah Al Mamun, Ashish P Anovadiya, Wildo N Araújo, Eduardo Azziz-Baumgartner, Clarisa Báez, Carlos Bantar, Mazen M Barhoush, Matteo Bassetti, Bojana Beovic, Roland Bingisser, Isabelle Bonmarin, Victor H Borja-Aburto, Bin Cao, Jordi Carratala, María R Cuezzo, Justin T Denholm, Samuel R Dominguez, Pericles A D Duarte, Gal Dubnov-Raz, Marcela Echavarria, Sergio Fanella, James Fraser, Zhancheng Gao, Patrick Gérardin, Maddalena Giannella, Sophie Gubbels, Jethro Herberg, Anjarath L Higuera Iglesias, Peter H Hoeger, Matthias Hoffmann, Xiaoyun Hu, Quazi T Islam, Mirela F Jiménez, Amr Kandeel, Gerben Keijzers, Hossein Khalili, Gulam Khandaker, Marian Knight, Gabriela Kusznierz, Ilija Kuzman, Arthur M C Kwan, Idriss Lahlou Amine, Eduard Langenegger, Kamran B Lankarani, Yee-Sin Leo, Rita Linko, Pei Liu, Faris Madanat, Toshie Manabe, Elga Mayo-Montero, Allison Mcgeer, Ziad A Memish, Gokhan Metan, Dragan Mikić, Kristin G I Mohn, Ahmadreza Moradi, Pagbajabyn Nymadawa, Bulent Ozbay, Mehpare Ozkan, Dhruv Parekh, Mical Paul, Wolfgang Poeppl, Fernando P Polack, Barbara A Rath, Alejandro H Rodríguez, Marilda M Siqueira, Joanna Skręt-Magierło, Ewa Talarek, Julian W Tang, Antoni Torres, Selda H Törün, Dat Tran, Timothy M Uyeki, Annelies Van Zwol, Wendy Vaudry, Daiva Velyvyte, Tjasa Vidmar, Paul Zarogoulidis, Jonathan S Nguyen-Van-Tam

Gerben Keijzers

BACKGROUND:

The impact of neuraminidase inhibitors (NAIs) on influenza-related pneumonia (IRP) is not established. Our objective was to investigate the association between NAI treatment and IRP incidence and outcomes in patients hospitalised with A(H1N1)pdm09 virus infection.

METHODS:

A worldwide meta-analysis of individual participant data from 20 634 hospitalised patients with laboratory-confirmed A(H1N1)pdm09 (n = 20 021) or clinically diagnosed (n = 613) 'pandemic influenza'. The primary outcome was radiologically confirmed IRP. Odds ratios (OR) were estimated using generalised linear mixed modelling, adjusting for NAI treatment propensity, antibiotics and corticosteroids.

RESULTS:

Of 20 634 included participants, 5978 (29·0 ...


5 Year Expression And Neutrophil Defect Repair After Gene Therapy In Alpha-1 Antitrypsin Deficiency, Christian Mueller, Gwladys Gernoux, Alisha M. Gruntman, Florie Borel, Emer P. Reeves, Roberto Calcedo, Farshid N. Rouhani, Anthony Yachnis, Margaret Humphries, Martha Campbell-Thompson, Louis M. Messina, Jeffrey D. Chulay, Bruce Trapnell, James M. Wilson, Noel G. McElvaney, Terence R. Flotte 2017 University of Massachusetts Medical School

5 Year Expression And Neutrophil Defect Repair After Gene Therapy In Alpha-1 Antitrypsin Deficiency, Christian Mueller, Gwladys Gernoux, Alisha M. Gruntman, Florie Borel, Emer P. Reeves, Roberto Calcedo, Farshid N. Rouhani, Anthony Yachnis, Margaret Humphries, Martha Campbell-Thompson, Louis M. Messina, Jeffrey D. Chulay, Bruce Trapnell, James M. Wilson, Noel G. Mcelvaney, Terence R. Flotte

Christian Mueller

Alpha-1 antitrypsin deficiency is a monogenic disorder resulting in emphysema due principally to the unopposed effects of neutrophil elastase. We previously reported achieving plasma wild-type alpha-1 antitrypsin concentrations at 2.5%-3.8% of the purported therapeutic level at 1 year after a single intramuscular administration of recombinant adeno-associated virus serotype 1 alpha-1 antitrypsin vector in alpha-1 antitrypsin deficient patients. We analyzed blood and muscle for alpha-1 antitrypsin expression and immune cell response. We also assayed previously reported markers of neutrophil function known to be altered in alpha-1 antitrypsin deficient patients. Here, we report sustained expression at 2.0%-2 ...


5 Year Expression And Neutrophil Defect Repair After Gene Therapy In Alpha-1 Antitrypsin Deficiency, Christian Mueller, Gwladys Gernoux, Alisha M. Gruntman, Florie Borel, Emer P. Reeves, Roberto Calcedo, Farshid N. Rouhani, Anthony Yachnis, Margaret Humphries, Martha Campbell-Thompson, Louis M. Messina, Jeffrey D. Chulay, Bruce Trapnell, James M. Wilson, Noel G. McElvaney, Terence R. Flotte 2017 University of Massachusetts Medical School

5 Year Expression And Neutrophil Defect Repair After Gene Therapy In Alpha-1 Antitrypsin Deficiency, Christian Mueller, Gwladys Gernoux, Alisha M. Gruntman, Florie Borel, Emer P. Reeves, Roberto Calcedo, Farshid N. Rouhani, Anthony Yachnis, Margaret Humphries, Martha Campbell-Thompson, Louis M. Messina, Jeffrey D. Chulay, Bruce Trapnell, James M. Wilson, Noel G. Mcelvaney, Terence R. Flotte

University of Massachusetts Medical School Faculty Publications

Alpha-1 antitrypsin deficiency is a monogenic disorder resulting in emphysema due principally to the unopposed effects of neutrophil elastase. We previously reported achieving plasma wild-type alpha-1 antitrypsin concentrations at 2.5%-3.8% of the purported therapeutic level at 1 year after a single intramuscular administration of recombinant adeno-associated virus serotype 1 alpha-1 antitrypsin vector in alpha-1 antitrypsin deficient patients. We analyzed blood and muscle for alpha-1 antitrypsin expression and immune cell response. We also assayed previously reported markers of neutrophil function known to be altered in alpha-1 antitrypsin deficient patients. Here, we report sustained expression at 2.0%-2 ...


Central Role Of Il-23 And Il-17 Producing Eosinophils As Immunomodulatory Effector Cells In Acute Pulmonary Aspergillosis And Allergic Asthma, Evelyn V. Santos Guerra, Chrono K. Lee, Charles A. Specht, Bhawna Yadav, Haibin Huang, Ali Akalin, Jun R. Huh, Christian Mueller, Stuart M. Levitz 2017 University of Massachusetts Medical School

Central Role Of Il-23 And Il-17 Producing Eosinophils As Immunomodulatory Effector Cells In Acute Pulmonary Aspergillosis And Allergic Asthma, Evelyn V. Santos Guerra, Chrono K. Lee, Charles A. Specht, Bhawna Yadav, Haibin Huang, Ali Akalin, Jun R. Huh, Christian Mueller, Stuart M. Levitz

Christian Mueller

Aspergillus fumigatus causes invasive pulmonary disease in immunocompromised hosts and allergic asthma in atopic individuals. We studied the contribution of lung eosinophils to these fungal diseases. By in vivo intracellular cytokine staining and confocal microscopy, we observed that eosinophils act as local sources of IL-23 and IL-17. Remarkably, mice lacking eosinophils had a >95% reduction in the percentage of lung IL-23p19+ cells as well as markedly reduced IL-23 heterodimer in lung lavage fluid. Eosinophils killed A. fumigatus conidia in vivo. Eosinopenic mice had higher mortality rates, decreased recruitment of inflammatory monocytes, and decreased expansion of lung macrophages after challenge with ...


Analysis Of The Local And Systemic Cytokine Response Profiles In Patients With Community-Acquired Pneumonia. Relationship With Disease Severity And Outcomes., Rafael Fernandez-Botran, Timothy Lee Wiemken, Robert R. Kelley, Paula Peyrani, Jose Bordon, Rodrigo Cavallazzi, Julio A. Ramirez 2017 University of Louisville

Analysis Of The Local And Systemic Cytokine Response Profiles In Patients With Community-Acquired Pneumonia. Relationship With Disease Severity And Outcomes., Rafael Fernandez-Botran, Timothy Lee Wiemken, Robert R. Kelley, Paula Peyrani, Jose Bordon, Rodrigo Cavallazzi, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

The goals of this study were to investigate the relationship of systemic and local cytokine responses with time to clinical stability (TCS) in patients with community-acquired pneumonia (CAP) and to develop a model to integrate multiple cytokine data into “cytokine response profiles” based on local vs. systemic and pro- vs. anti-inflammatory cytokine patterns in order to better understand their relationships with measures of CAP severity and outcomes. Forty hospitalized patients enrolled through the Community Acquired Pneumonia Inflammatory Study Group (CAPISG) were analyzed. Based on the ranked distribution of the levels of eight different pro-inflammatory cytokines and chemokines (IL-1b, IL-6, IL-8 ...


The Kinetics Of Type I Interferons During Influenza Virus Infection, Margaret A. Myers 2017 St. Jude Children's Research Hospital, Rhodes College

The Kinetics Of Type I Interferons During Influenza Virus Infection, Margaret A. Myers

Biology and Medicine Through Mathematics Conference

No abstract provided.


Evolution Of The Alpha-1 Antitrypsin Muscle Gene Therapy: Translation From Clinical Trial To Benchtop And Back Again, Alisha M. Gruntman, Gwladys Gernoux, Gensheng Wang, Janet Benson, Jeff Chulay, Dave Knop, Christian Mueller, Terence R. Flotte 2017 University of Massachusetts Medical School

Evolution Of The Alpha-1 Antitrypsin Muscle Gene Therapy: Translation From Clinical Trial To Benchtop And Back Again, Alisha M. Gruntman, Gwladys Gernoux, Gensheng Wang, Janet Benson, Jeff Chulay, Dave Knop, Christian Mueller, Terence R. Flotte

UMass Center for Clinical and Translational Science Research Retreat

Alpha-one antitrypsin (AAT) deficiency is a genetic disease affecting the lungs due to inadequate anti-protease activity in the pulmonary interstitium. On-going human trials use intra-muscular delivery of adeno-associated virus (rAAV1), allowing expressing myofibers to secrete normal (M)AAT protein. In the Phase IIa trial, patients in the highest dose cohort (6x1012vg/kg) were given 100 intra-muscular (IM) injections of undiluted vector, with serum AAT levels still substantially below target levels. Previous work has shown that delivering rAAV vector to the musculature via limb perfusion leads to widespread gene expression in myofibers. We hypothesize that widespread delivery would result ...


Home Interventions For Older Adults With Asthma, David Turcotte, Susan Woskie, Emily Chaves, Kelechi Adejumo, Rebecca Gore 2017 University of Massachusetts Lowell

Home Interventions For Older Adults With Asthma, David Turcotte, Susan Woskie, Emily Chaves, Kelechi Adejumo, Rebecca Gore

UMass Center for Clinical and Translational Science Research Retreat

Older asthmatic adults are more likely to experience respiratory failure than younger adults and children with asthma. Older adults spend up to 90% of their time in the home where many allergens are found. While there is sufficient evidence that home interventions improve the health of asthmatic children, there is insufficient evidence for the effectiveness of home interventions with adults. Our research evaluates the hypothesis that multi-trigger, multifaceted home interventions improve respiratory health and reduce home asthma triggers for older adults.

Methods: We evaluated the effectiveness of conducting interventions in the homes of 86 diverse, low-income older adults (age 62 ...


Procalcitonin Levels; An Alternative Diagnostic Approach For Community Acquired Pneumonia In Acute Care Settings And Determination Of Antibiotic Therapy, Jamie Anne Rhodine 2017 University of Wyoming

Procalcitonin Levels; An Alternative Diagnostic Approach For Community Acquired Pneumonia In Acute Care Settings And Determination Of Antibiotic Therapy, Jamie Anne Rhodine

Honors Theses AY 16/17

Procalcitonin (PCT) levels are an accurate reflection of bacterial replication within the human body. By deciphering between bacterial and viral invasion, antibiotic therapy will be reduced contributing to the reduction of antibiotic resistance. For atypical patients with community acquired pneumonia (CAP), PCT levels will detect when antibiotic therapy is effective and when it is safe to discontinue antibiotics. Hospital stay length will be reduced and patients to nurse ratios will improve. One simple diagnostic PCT test used as an adjunct with traditional diagnostic testing for CAP will help minimize morbidity and mortality rates among patients. Traditionally used with septic patients ...


Informal Caregivers’ Experience During Acute Exacerbation Of Copd In Older Adults: A Dissertation, Helen M. Flaherty 2017 University of Massachusetts Medical School

Informal Caregivers’ Experience During Acute Exacerbation Of Copd In Older Adults: A Dissertation, Helen M. Flaherty

Graduate School of Nursing Dissertations

Chronic obstructive pulmonary disease (COPD) has been recognized as a leading cause of mortality in older adults involving acute exacerbations as life-threatening events that lead to frequent hospitalization for care. Informal caregivers have been essential to helping older adults with COPD during an acute exacerbation of chronic obstructive pulmonary disease (AECOPD). A lack of empirical knowledge exists regarding the experience of informal caregivers of older adults with AECOPD in situation awareness for recognizing, understanding, and responding to an AECOPD in an emergent situation. This qualitative descriptive study explored situation awareness and its components of perception, comprehension and projection of next ...


Community Acquired Pneumonia, Allison Foering 2017 Liberty University

Community Acquired Pneumonia, Allison Foering

The Kabod

Community acquired pneumonia is discussed, including the pathophysiology, treatment, patient education, and nursing practice points.


Pulmonary Microrna Profiles Identify Involvement Of Creb1 And Sec14l3 In Bronchial Epithelial Changes In Allergic Asthma., Sabine Bartel, Nikola Schulz, Francesca Alessandrini, Andrea C Schamberger, Philipp Pagel, Fabian J Theis, Katrin Milger, Elfriede Noessner, Stephen M Stick, Anthony Kicic, Oliver Eickelberg, Robert J Freishtat, Susanne Krauss-Etschmann 2017 George Washington University

Pulmonary Microrna Profiles Identify Involvement Of Creb1 And Sec14l3 In Bronchial Epithelial Changes In Allergic Asthma., Sabine Bartel, Nikola Schulz, Francesca Alessandrini, Andrea C Schamberger, Philipp Pagel, Fabian J Theis, Katrin Milger, Elfriede Noessner, Stephen M Stick, Anthony Kicic, Oliver Eickelberg, Robert J Freishtat, Susanne Krauss-Etschmann

Medicine Faculty Publications

Asthma is highly prevalent, but current therapies cannot influence the chronic course of the disease. It is thus important to understand underlying early molecular events. In this study, we aimed to use microRNAs (miRNAs) - which are critical regulators of signaling cascades - to identify so far uncharacterized asthma pathogenesis pathways. Therefore, deregulation of miRNAs was assessed in whole lungs from mice with ovalbumin (OVA)-induced allergic airway inflammation (AAI). In silico predicted target genes were confirmed in reporter assays and in house-dust-mite (HDM) induced AAI and primary human bronchial epithelial cells (NHBE) cultured at the air-liquid interface. We identified and validated ...


Cigarette Smoke Impairs A2a Adenosine Receptor Mediated Wound Repair Through Up-Regulation Of Duox-1 Expression., Zhi Tian, Hui Zhang, Jendayi Dixon, Nicole Traphagen, Todd A. Wyatt, Kusum K. Kharbanda, Samantha Simet, Narasaiah Kolliputi, Diane S Allen-Gipson 2017 University of South Florida

Cigarette Smoke Impairs A2a Adenosine Receptor Mediated Wound Repair Through Up-Regulation Of Duox-1 Expression., Zhi Tian, Hui Zhang, Jendayi Dixon, Nicole Traphagen, Todd A. Wyatt, Kusum K. Kharbanda, Samantha Simet, Narasaiah Kolliputi, Diane S Allen-Gipson

Journal Articles: Pulmonary & Critical Care Med

Cigarette smoke (CS) exposure and intrinsic factors such as the NADPH oxidases produce high levels of reactive oxygen species (ROS), ensuing inflammatory tissue injury. We previously demonstrated that CS-generated ROS, particularly hydrogen peroxide (H2O2), impaired adenosine stimulated wound repair. We hypothesized that CS exposure modulates expression of Dual oxidase 1 (Duox-1), a NADPH oxidases known to generate H2O2. To test this hypothesis, we used human bronchial epithelial cell line Nuli-1 and C57BL/6 mice. Cells were treated with 5% CS extract (CSE) for various periods of time, and mice were exposed to whole body CS for six weeks. Both CSE ...


Effect Of Low-Level Co2 On Innate Inflammatory Protein Response To Organic Dust From Swine Confinement Barns., David Schneberger, Jane M. DeVasure, Kristina L. Bailey, Debra J. Romberger, Todd A. Wyatt 2017 University of Nebraska Medical Center

Effect Of Low-Level Co2 On Innate Inflammatory Protein Response To Organic Dust From Swine Confinement Barns., David Schneberger, Jane M. Devasure, Kristina L. Bailey, Debra J. Romberger, Todd A. Wyatt

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Organic hog barn dust (HDE) exposure induces lung inflammation and long-term decreases in lung function in agricultural workers. While concentrations of common gasses in confined animal facilities are well characterized, few studies have been done addressing if exposure to elevated barn gasses impacts the lung immune response to organic dusts. Given the well documented effects of hypercapnia at much higher levels we hypothesized that CO2 at 8 h exposure limit levels (5000 ppm) could alter innate immune responses to HDE.

METHODS: Using a mouse model, C57BL/6 mice were nasally instilled with defined barn dust extracts and then housed ...


Effect Of Low-Level Co2 On Innate Inflammatory Protein Response To Organic Dust From Swine Confinement Barns., David Schneberger, Jane M. DeVasure, Kristina L. Bailey, Debra J. Romberger, Todd A. Wyatt 2017 University of Nebraska Medical Center

Effect Of Low-Level Co2 On Innate Inflammatory Protein Response To Organic Dust From Swine Confinement Barns., David Schneberger, Jane M. Devasure, Kristina L. Bailey, Debra J. Romberger, Todd A. Wyatt

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Organic hog barn dust (HDE) exposure induces lung inflammation and long-term decreases in lung function in agricultural workers. While concentrations of common gasses in confined animal facilities are well characterized, few studies have been done addressing if exposure to elevated barn gasses impacts the lung immune response to organic dusts. Given the well documented effects of hypercapnia at much higher levels we hypothesized that CO2 at 8 h exposure limit levels (5000 ppm) could alter innate immune responses to HDE.

METHODS: Using a mouse model, C57BL/6 mice were nasally instilled with defined barn dust extracts and then housed ...


The Role Of Asb3 Gene Single Nucleotide Polymorphism In The Progression To Bronchopulmonary Dysplasia In Extremely Low Birth Weight Infants, Anna Zylak, Leewen Hsu, Asma Amin, Shaili Amatya, Sharina Rajbhandari, Alexander Feldman, Umesh Paudel, Lance A. Parton 2017 New York Medical College

The Role Of Asb3 Gene Single Nucleotide Polymorphism In The Progression To Bronchopulmonary Dysplasia In Extremely Low Birth Weight Infants, Anna Zylak, Leewen Hsu, Asma Amin, Shaili Amatya, Sharina Rajbhandari, Alexander Feldman, Umesh Paudel, Lance A. Parton

NYMC Faculty Posters

No abstract provided.


Rock2 Gene Single Nucleotide Polymorphisms And Association With Bronchopulmonary Dysplasia In Extremely Low Birth Weight Infants, Sharina Rajbhandari, Asma Amin, Shaili Amatya, Leewen Hsu, Anna Zylak, Umesh Paudel, Lance A. Parton 2017 New York Medical College

Rock2 Gene Single Nucleotide Polymorphisms And Association With Bronchopulmonary Dysplasia In Extremely Low Birth Weight Infants, Sharina Rajbhandari, Asma Amin, Shaili Amatya, Leewen Hsu, Anna Zylak, Umesh Paudel, Lance A. Parton

NYMC Faculty Posters

No abstract provided.


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