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272 results on '"Woolard, A"'

5. Lung and lymph node explants to study the interaction between host cells and canine distemper virus

Author

Omar, Gonzales-Viera, Kevin D, Woolard, and M Kevin, Keel

Subjects
General Veterinary
Abstract

Canine distemper virus (CDV, family Paramyxoviridae) is a widely known fatal disease in unvaccinated dogs and wild carnivores. The virus enters via the respiratory tract and rapidly spreads to the lymphoid organs. To investigate viral entry into these tissues, a dog tissue explant model was developed for lung and lymph nodes. Canine lung explants were cultured with CDV for three days. During this time CDV antigens were visible on alveolar cells, which were CD163-positive and SLAM-positive (signaling lymphocytic activation molecule), demonstrating that they were macrophages. The lymph node explants were maintained for five days. During this time the viral replication increased progressively by each day post infection and syncytia were observed by day three, post exposure. The microscopic distribution of CDV-positive cells in the lymph nodes, including the syncytia, and co-expression of CD163 and SLAM, demonstrated that they were macrophages. These findings suggest that alveolar macrophages are the first cells in the lung to become infected during CDV infection, and lymph node explants showed similar replication rates and virus-cell interactions as seen in experimental live animals. This demonstrates the utility of canine respiratory and lymphoid explant model to evaluate cell entry and viral replication of CDV and other morbilliviruses in dogs or other susceptible carnivores.

Published
2023
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7. The relationship between pitch contours in infant-directed speech and early signs of autism in infancy

Author

Woolard, Alix, primary, Benders, Titia, additional, Campbell, Linda E., additional, Whalen, Olivia M., additional, Mallise, Carly, additional, Karayanidis, Frini, additional, Barker, Daniel, additional, Murphy, Vanessa E., additional, Tait, Jordan, additional, Gibson, Peter, additional, Korostenski, Larissa, additional, and Lane, Alison E., additional

Published
2023
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9. An Unusual Finding in a Patient Presenting for Pulmonary Thromboendarterectomy: Pulmonary Venous Thrombosis

Author

Susan S. Eagle, Kara K. Siegrist, Karl D Hillenbrand, Ashish S. Shah, and Austin A. Woolard

Subjects
medicine.medical_specialty, genetic structures, Hypertension, Pulmonary, medicine.medical_treatment, Radiography, Catheter ablation, Endarterectomy, Malignancy, Asymptomatic, Biopsy, medicine, Humans, Lung, Venous Thrombosis, Pulmonary thromboendarterectomy, medicine.diagnostic_test, business.industry, Atrial fibrillation, medicine.disease, Anesthesiology and Pain Medicine, Etiology, Radiology, medicine.symptom, Pulmonary Embolism, Cardiology and Cardiovascular Medicine, business
Abstract

Pulmonary venous thrombosis (PVT) is a rare but potentially devastating disease state with a largely unknown incidence. The most common etiologies of PVT are secondary to complications of lung surgery, malignancy, catheter ablation for atrial fibrillation, and idiopathic causes. Diagnosis can be challenging because presenting symptoms often are vague and nonspecific, or even asymptomatic, and traditional diagnostic modalities, such as chest radiography and arterial phase computed tomography scans, are poor techniques for diagnosis. The authors present a case of a patient presenting for pulmonary thromboendarterectomy for a presumed diagnosis of chronic thromboembolic pulmonary hypertension who was found incidentally to have a PVT, on intraoperative transesophageal echocardiography. Due to significant thrombus burden, the new finding of PVT, and known association of PVT and malignancy, a biopsy of mediastinal lymph nodes was obtained, which revealed metastatic cervical carcinoma. The pulmonary endarterectomy procedure was aborted.

Published
2022
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14. Methamphetamine causes cardiovascular dysfunction via cystathionine gamma lyase and hydrogen sulfide depletion

Author

Kolluru, Gopi K., primary, Glawe, John D., additional, Pardue, Sibile, additional, Kasabali, Ahmad, additional, Alam, Shafiul, additional, Rajendran, Saranya, additional, Cannon, Allison L., additional, Abdullah, Chowdhury S., additional, Traylor, James G., additional, Shackelford, Rodney E., additional, Woolard, Matthew D., additional, Orr, A. Wayne, additional, Goeders, Nicholas E., additional, Dominic, Paari, additional, Bhuiyan, Md Shenuarin S., additional, and Kevil, Christopher G., additional

Published
2022
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19. Effects of intensive versus standard blood pressure control on domain-specific cognitive function: a substudy of the SPRINT randomised controlled trial

Author

Stephen R Rapp, Sarah A Gaussoin, Bonnie C Sachs, Gordon Chelune, Mark A Supiano, Alan J Lerner, Virginia G Wadley, Valarie M Wilson, Lawrence J Fine, Jeff C Whittle, Alexander P Auchus, Srinivasan Beddhu, Dan R Berlowitz, Adam P Bress, Karen C Johnson, Marie Krousel-Wood, Jennifer Martindale-Adams, Eliza C Miller, Dena E Rifkin, Joni K Snyder, Leonardo Tamariz, Dawn F Wolfgram, Maryjo L Cleveland, Mia Yang, Linda O Nichols, Robert Nick Bryan, David M Reboussin, Jeff D Williamson, Nicholas M Pajewski, Alfred K Cheung, Laura H Coker, Michael G Crowe, William C Cushman, Jeffery A Cutler, Christos Davatzikos, Lisa Desiderio, Jimit Doshi, Guray Erus, Darrin Harris, Paul L Kimmel, Manjula K Tamura, Lenore J Launer, Cora E Lewis, Claudia S Moy, Suzanne Oparil, Paula K Ogrocki, Mahboob Rahman, Ilya M Nasrallah, Michael V Rocco, Kaycee M Sink, Carolyn H Still, Jennifer Walker, Daniel E Weiner, Paul K Whelton, Valerie M Wilson, Nancy Woolard, Jackson T Wright, Clinton B Wright, and R Nick Bryan

Subjects
Male, medicine.medical_specialty, Trail Making Test, Blood Pressure, 030204 cardiovascular system & hematology, Verbal learning, law.invention, 03 medical and health sciences, Cognition, 0302 clinical medicine, Randomized controlled trial, law, medicine, Humans, Cognitive Dysfunction, Stroke, Veterans Affairs, Antihypertensive Agents, Aged, Aged, 80 and over, business.industry, Standard treatment, Blood Pressure Monitoring, Ambulatory, Middle Aged, Mental Status and Dementia Tests, medicine.disease, United States, United States Department of Veterans Affairs, Treatment Outcome, Blood pressure, Sprint, Hypertension, Physical therapy, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract

Summary Background Results from the Systolic Blood Pressure Intervention Trial (SPRINT) showed that intensive control of systolic blood pressure significantly reduced the occurrence of mild cognitive impairment, but not probable dementia. We investigated the effects of intensive lowering of systolic blood pressure on specific cognitive functions in a preplanned substudy of participants from SPRINT. Methods SPRINT was an open-label, multicentre, randomised controlled trial undertaken at 102 sites, including academic medical centres, Veterans Affairs medical centres, hospitals, and independent clinics, in the USA and Puerto Rico. Participants were adults aged 50 years or older with systolic blood pressure higher than 130 mm Hg, but without diabetes, history of stroke, or dementia. Participants were randomly assigned (1:1) to a systolic blood pressure goal of less than 120 mm Hg (intensive treatment) versus less than 140 mm Hg (standard treatment). All major classes of antihypertensive agents were included. A subgroup of randomly assigned participants including, but not limited to, participants enrolled in an MRI substudy was then selected for a concurrent substudy of cognitive function (target 2800 participants). Each individual was assessed with a screening cognitive test battery and an extended cognitive test battery at baseline and biennially during the planned 4-year follow-up. The primary outcomes for this substudy were standardised composite scores for memory (Logical Memory I and II, Modified Rey-Osterrieth Complex Figure [immediate recall], and Hopkins Verbal Learning Test-Revised [delayed recall]) and processing speed (Trail Making Test and Digit Symbol Coding). SPRINT was registered with ClinicalTrials.gov , NCT01206062 . Findings From Nov 23, 2010, to Dec 28, 2012, 2921 participants (mean age 68·4 years [SD 8·6], 1080 [37%] women) who had been randomly assigned in SPRINT were enrolled in the substudy (1448 received intensive treatment and 1473 received standard treatment). SPRINT was terminated early due to benefit observed in the primary outcome (composite of cardiovascular events). After a median follow-up of 4·1 years (IQR 3·7–5·8), there was no between-group difference in memory, with an annual decline in mean standardised domain score of −0·005 (95% CI −0·010 to 0·001) in the intensive treatment group and −0·001 (–0·006 to 0·005) in the standard treatment group (between-group difference −0·004, 95% CI −0·012 to 0·004; p=0·33). Mean standardised processing speed domain scores declined more in the intensive treatment group (between-group difference −0·010, 95% CI −0·017 to −0·002; p=0·02), with an annual decline of −0·025 (–0·030 to −0·019) for the intensive treatment group and −0·015 (–0·021 to 0·009) for the standard treatment group. Interpretation Intensive treatment to lower systolic blood pressure did not result in a clinically relevant difference compared with standard treatment in memory or processing speed in a subgroup of participants from SPRINT. The effect of blood pressure lowering might not be evident in specific domains of cognitive function, but instead distributed across multiple domains. Funding National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute on Aging, National Institute of Neurological Disorders and Stroke, and the Alzheimer's Association.

Published
2020
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22. Kidney Disease, Hypertension Treatment, and Cerebral Perfusion and Structure

Author

Kurella Tamura, Manjula, primary, Gaussoin, Sarah, additional, Pajewski, Nicholas M., additional, Zaharchuk, Greg, additional, Freedman, Barry I., additional, Rapp, Stephen R., additional, Auchus, Alexander P., additional, Haley, William E., additional, Oparil, Suzanne, additional, Kendrick, Jessica, additional, Roumie, Christianne L., additional, Beddhu, Srinivasan, additional, Cheung, Alfred K., additional, Williamson, Jeff D., additional, Detre, John A., additional, Dolui, Sudipto, additional, Bryan, R. Nick, additional, Nasrallah, Ilya M., additional, Whelton, Paul, additional, Johnson, Karen C., additional, Snyder, Joni, additional, Bild, Diane, additional, Bonds, Denise, additional, Cook, Nakela, additional, Cutler, Jeffrey, additional, Fine, Lawrence, additional, Kaufmann, Peter, additional, Kimmel, Paul, additional, Launer, Lenore, additional, Moy, Claudia, additional, Riley, William, additional, Ryan, Laurie, additional, Tolunay, Eser, additional, Yang, Song, additional, Reboussin, David, additional, Williamson, Jeff, additional, Ambrosius, Walter T., additional, Applegate, William, additional, Evans, Greg, additional, Foy, Capri, additional, Kitzman, Dalane, additional, Lyles, Mary, additional, Pajewski, Nick, additional, Rapp, Steve, additional, Rushing, Scott, additional, Shah, Neel, additional, Sink, Kaycee M., additional, Vitolins, Mara, additional, Wagenknecht, Lynne, additional, Wilson, Valerie, additional, Perdue, Letitia, additional, Woolard, Nancy, additional, Craven, Tim, additional, Garcia, Katelyn, additional, Lovato, Laura, additional, Newman, Jill, additional, Lovato, James, additional, Lu, Lingyi, additional, McLouth, Chris, additional, Russell, Greg, additional, Amoroso, Bobby, additional, Davis, Patty, additional, Griffin, Jason, additional, Harris, Darrin, additional, King, Mark, additional, Lane, Kathy, additional, Roberson, Wes, additional, Steinberg, Debbie, additional, Ashford, Donna, additional, Babcock, Phyllis, additional, Chamberlain, Dana, additional, Christensen, Vickie, additional, Cloud, Loretta, additional, Collins, Christy, additional, Cook, Delilah, additional, Currie, Katherine, additional, Felton, Debbie, additional, Harpe, Stacy, additional, Howard, Marjorie, additional, Lewis, Michelle, additional, Nance, Pamela, additional, Puccinelli-Ortega, Nicole, additional, Russell, Laurie, additional, Walker, Jennifer, additional, Craven, Brenda, additional, Goode, Candace, additional, Troxler, Margie, additional, Davis, Janet, additional, Hutchens, Sarah, additional, Killeen, Anthony A., additional, Lukkari, Anna M., additional, Ringer, Robert, additional, Dillard, Brandi, additional, Archibeque, Norbert, additional, Warren, Stuart, additional, Sather, Mike, additional, Pontzer, James, additional, Taylor, Zach, additional, Soliman, Elsayed Z., additional, Zhang, Zhu-Ming, additional, Li, Yabing, additional, Campbell, Chuck, additional, Hensley, Susan, additional, Hu, Julie, additional, Keasler, Lisa, additional, Barr, Mary, additional, Taylor, Tonya, additional, Davatzikos, Christos, additional, Nasarallah, Ilya, additional, Desiderio, Lisa, additional, Elliott, Mark, additional, Borthakur, Ari, additional, Battapady, Harsha, additional, Erus, Guray, additional, Smith, Alex, additional, Wang, Ze, additional, Doshi, Jimit, additional, Wright, Jackson T., additional, Rahman, Mahboob, additional, Lerner, Alan J., additional, Still, Carolyn, additional, Wiggers, Alan, additional, Zamanian, Sara, additional, Bee, Alberta, additional, Dancie, Renee, additional, Thomas, George, additional, Schreiber, Martin, additional, Navaneethan, Sankar Dass, additional, Hickner, John, additional, Lioudis, Michael, additional, Lard, Michelle, additional, Marczewski, Susan, additional, Maraschky, Jennifer, additional, Colman, Martha, additional, Aaby, Andrea, additional, Payne, Stacey, additional, Ramos, Melanie, additional, Horner, Carol, additional, Drawz, Paul, additional, Raghavendra, Pratibha P., additional, Ober, Scott, additional, Mourad, Ronda, additional, Pallaki, Muralidhar, additional, Russo, Peter, additional, Raghavendra, Pratibha, additional, Fantauzzo, Pual, additional, Tucker, Lisa, additional, Schwing, Bill, additional, Sedor, John R., additional, Horwitz, Edward J., additional, Schellling, Jeffrey R., additional, O’Toole, John F., additional, Humbert, Lisa, additional, Tutolo, Wendy, additional, White, Suzanne, additional, Gay, Alishea, additional, Clark, Walter, additional, Hughes, Robin, additional, Dobre, Mirela, additional, Still, Carolyn H., additional, Williams, Monique, additional, Bhatt, Udayan, additional, Hebert, Lee, additional, Agarwal, Anil, additional, Murphy, Melissa Brown, additional, Ford, Nicole, additional, Stratton, Cynthia, additional, Baxter, Jody, additional, Lykins, Alicia A., additional, McKinley Neal Leena Hirmath, Alison, additional, Kwame, Osei, additional, Soe, Kyaw, additional, Miser, William F., additional, Sagrilla, Colleen, additional, Johnston, Jan, additional, Anaya, Amber, additional, Mintos, Ashley, additional, Howell, Angel A., additional, Rogers, Kelly, additional, Taylor, Sara, additional, Ebersbacher, Donald, additional, Long, Lucy, additional, Bednarchik, Beth, additional, Schnall, Adrian, additional, Smith, Jonathan, additional, Peysha, Lori, additional, Leach, Lisa, additional, Tribout, Megan, additional, Harwell, Carla, additional, Ellington, Pinkie, additional, Banerji, Mary Ann, additional, Ghody, Pranav, additional, Rambaud, Melissa Vahídeh, additional, Townsend, Raymond, additional, Cohen, Debbie, additional, Huan, Yonghong, additional, Duckworth, Mark, additional, Ford, Virginia, additional, Leshner, Juliet, additional, Davison, Ann, additional, Veen, Sarah Vander, additional, Gadegbeku, Crystal A., additional, Gillespie, Avi, additional, Paranjape, Anuradha, additional, Amoroso, Sandra, additional, Pfeffer, Zoe, additional, Quinn, Sally B., additional, He, Jiang, additional, Chen, Jing, additional, Lustigova, Eva, additional, Malone, Erin, additional, Krousel-Wood, Marie, additional, Deichmann, Richard, additional, Ronney, Patricia, additional, Muery, Susan, additional, Trapani, Donnalee, additional, Rocco, Michael, additional, Goff, David, additional, Rodriguez, Carlos, additional, Coker, Laura, additional, Hawfield, Amret, additional, Yeboah, Joseph, additional, Crago, Lenore, additional, Summerson, John, additional, Hege, Anita, additional, Diamond, Matt, additional, Mulloy, Laura, additional, Hodges, Marcela, additional, Collins, Michelle, additional, Weathers, Charlene, additional, Anderson, Heather, additional, Stone, Emily, additional, Walker, Walida, additional, McWilliams, Andrew, additional, Dulin, Michael, additional, Kuhn, Lindsay, additional, Standridge, Susan, additional, Lowe, Lindsay, additional, Everett, Kelly, additional, Preston, Kelry, additional, Norton, Susan, additional, Gaines, Silena, additional, Rizvi, Ali A., additional, Sides, Andrew W., additional, Herbert, Diamond, additional, Hix, Matthew M., additional, Whitmire, Melanie, additional, Arnold, Brittany, additional, Hutchinson, Philip, additional, Espiritu, Joseph, additional, Feinglos, Mark, additional, Kovalik, Eugene, additional, Gedon-Lipscomb, Georgianne, additional, Evans, Kathryn, additional, Thacker, Connie, additional, Zimmer, Ronna, additional, Furst, Mary, additional, Mason, MaryAnn, additional, Powell, James, additional, Bolin, Paul, additional, Zhang, Junhong, additional, Pinion, Mary, additional, Davis, Gail, additional, Bryant, Winifred, additional, Phelps, Presley, additional, Garris-Sutton, Connie, additional, Atkinson, Beatrice, additional, Contreras, Gabriele, additional, Suarez, Maritza, additional, Schulman, Ivonne, additional, Koggan, Don, additional, Vassallo, Jackie, additional, Peruyera, Gloria, additional, Whittington, Sheri, additional, Bethea, Cassandra, additional, Gilliam, Laura, additional, Pedley, Carolyn, additional, Zurek, Geraldine, additional, Baird, Miriam, additional, Herring, Charles, additional, Smoak, Mary Martha, additional, Williams, Julie, additional, Rogers, Samantha, additional, Gordon, Lindsay, additional, Kennedy, Erin, additional, Belle, Beverly, additional, McCorkle-Doomy, Jessica, additional, Adams, Jonathan, additional, Lopez, Ramon, additional, Janavs, Juris, additional, Rahbari-Oskoui, Frederic, additional, Chapman, Arlene, additional, Dollar, Allen, additional, Williams, Olubunmi, additional, Han, Yoosun, additional, Haley, William, additional, Fitzpatrick, Peter, additional, Blackshear, Joseph, additional, Shapiro, Brian, additional, Harrell, Anna, additional, Palaj, Arta, additional, Henderson, Katelyn, additional, Johnson, Ashley, additional, Gonzalez, Heath, additional, Robinson, Jermaine, additional, Tamariz, Leonardo, additional, Denizard, Jennifer, additional, Barakat, Rody, additional, Krishnamoorthy, Dhurga, additional, Greenway, Frank, additional, Monce, Ron, additional, Church, Timothy, additional, Hendrick, Chelsea, additional, Yoches, Aimee, additional, Sones, Leighanne, additional, Baltazar, Markee, additional, Pemu, Priscilla, additional, Jones, Connie, additional, Akpalu, Derrick, additional, Chelune, Gordon, additional, Childs, Jeffrey, additional, Gren, Lisa, additional, Randall, Anne, additional, Dember, Laura, additional, Soares, Denise, additional, Yee, Jerry, additional, Umanath, Kausik, additional, Ogletree, Naima, additional, Thaxton, Schawana, additional, Campana, Karen, additional, Sheldon, Dayna, additional, MacArthur, Krista, additional, Muhlestein, J. Brent, additional, Allred, Nathan, additional, Clements, Brian, additional, Dhar, Ritesh, additional, Meredith, Kent, additional, Le, Viet, additional, Miner, Edward, additional, Orford, James, additional, Riessen, Erik R., additional, Ballantyne, Becca, additional, Chisum, Ben, additional, Johnson, Kevin, additional, Peeler, Dixie, additional, Chertow, Glenn, additional, Tamura, Manju, additional, Chang, Tara, additional, Erickson, Kevin, additional, Shen, Jenny, additional, Stafford, Randall S., additional, Zaharchuk, Gregory, additional, Del Cid, Margareth, additional, Dentinger, Michelle, additional, Sabino, Jennifer, additional, Sahay, Rukmani, additional, Telminova, Ekaterina, additional, Weiner, Daniel E., additional, Sarnak, Mark, additional, Chan, Lily, additional, Civiletto, Amanda, additional, Heath, Alyson, additional, Kantor, Amy, additional, Jain, Priyanka, additional, Kirkpatrick, Bethany, additional, Well, Andrew, additional, Yuen, Barry, additional, Chonchol, Michel, additional, Farmer, Beverly, additional, Farmer, Heather, additional, Greenwald, Carol, additional, Malaczewski, Mikaela, additional, Lash, James, additional, Porter, Anna, additional, Ricardo, Ana, additional, Rosman, Robert T., additional, Cohan, Janet, additional, Barrera, Nieves Lopez, additional, Meslar, Daniel, additional, Meslar, Patricia, additional, Conroy, Margaret, additional, Unruh, Mark, additional, Hess, Rachel, additional, Jhamb, Manisha, additional, Thomas, Holly, additional, Fazio, Pam, additional, Klixbull, Elle, additional, Komlos-Weimer, Melissa, additional, Mandich, LeeAnne, additional, Vita, Tina, additional, Toto, Robert, additional, Van Buren, Peter, additional, Inrig, Julia, additional, Cruz, Martha, additional, Lightfoot, Tammy, additional, Wang, Nancy, additional, Webster, Lori, additional, Raphael, Kalani, additional, Stults, Barry, additional, Zaman, Tahir, additional, Simmons, Debra, additional, Lavasani, Tooran, additional, Filipowicz, Rebecca, additional, Wei, Guo, additional, Miller, Gracie Mary, additional, Harerra, Jenice, additional, Christensen, Jeff, additional, Giri, Ajay, additional, Chen, Xiaorui, additional, Anderton, Natalie, additional, Jensen, Arianna, additional, Lewis, Julia, additional, Burgner, Anna, additional, Dwyer, Jamie P., additional, Schulman, Gerald, additional, Herrud, Terri, additional, Leavell, Ewanda, additional, McCray, Tiffany, additional, McNeil-Simaan, Edwina, additional, Poudel, Munmun, additional, Reed, Malia, additional, Sika, Mohammed, additional, Woods, Delia, additional, Zirkenbach, Janice L., additional, Raj, Dominic S., additional, Cohen, Scott, additional, Patel, Samir, additional, Velasquez, Manuel, additional, Bastian, Roshni S., additional, Wing, Maria, additional, Roy-Chaudhury, Akshay, additional, Depner, Thomas, additional, Dalyrymple, Lorien, additional, Kaysen, George, additional, Anderson, Susan, additional, Nord, John, additional, Ix, Joachim H., additional, Goldenstein, Leonard, additional, Miracle, Cynthia M., additional, Forbang, Nketi, additional, Mircic, Maja, additional, Thomas, Brenda, additional, Tran, Tiffany, additional, Rastogi, Anjay, additional, Kim, Mihae, additional, Rashid, Mohamad, additional, Lizarraga, Bianca, additional, Hocza, Amy, additional, Sarmosyan, Kristine, additional, Norris, Jason, additional, Sharma, Tushar, additional, Chioy, Amanda, additional, Bernard, Eric, additional, Cabrera, Eleanore, additional, Lopez, Christina, additional, Nunez, Susana, additional, Riad, Joseph, additional, Schweitzer, Suzanne, additional, Sirop, Siran, additional, Thomas, Sarah, additional, Wada, Lauren, additional, Kramer, Holly, additional, Bansal, Vinod, additional, Taylor, Corliss E., additional, Segal, Mark S., additional, Hall, Karen L., additional, Kazory, Amir, additional, Gilbert, Lesa, additional, Owens, Linda, additional, Poulton, Danielle, additional, Whidden, Elaine, additional, Wiggins, Jocelyn, additional, Blaum, Caroline, additional, Nyquist, Linda, additional, Min, Lillian, additional, Gure, Tanya, additional, Lewis, Ruth, additional, Mawby, Jennifer, additional, Robinson, Eileen, additional, Lewis, Cora E., additional, Bradley, Virginia, additional, Calhoun, David, additional, Glasser, Stephen, additional, Jenkins, Kim, additional, Ramsey, Tom, additional, Qureshi, Nauman, additional, Ferguson, Karen, additional, Haider, Sumrah, additional, James, Mandy, additional, Jones, Christy, additional, Renfroe, Kim, additional, Seay, April, additional, Weigart, Carrie, additional, Thornley-Brown, Denyse, additional, Rizik, Dana, additional, Cotton, Bari, additional, Fitz-Gerald, Meredith, additional, Grimes, Tiffany, additional, Johnson, Carolyn, additional, Kennedy, Sara, additional, Mason, Chanel, additional, Rosato-Burson, Lesa, additional, Willingham, Robin, additional, Judd, Eric, additional, Breaux-Shropshire, Tonya, additional, Cook, Felice, additional, Medina, Julia, additional, Ghazi, Lama, additional, Bhatt, Hemal, additional, Lewis, James, additional, Brantley, Roman, additional, Brouilette, John, additional, Glaze, Jeffrey, additional, Hall, Stephanie, additional, Hiott, Nancy, additional, Tharpe, David, additional, Boddy, Spencer, additional, Mack, Catherine, additional, Womack, Catherine, additional, Asao, Keiko, additional, Griffin, Beate, additional, Hendrix, Carol, additional, Johnson, Karen, additional, Jones, Lisa, additional, Towers, Chelsea, additional, Punzi, Henry, additional, Cassidy, Kathy, additional, Schumacher, Kristin, additional, Irizarry, Carmen, additional, Colon, Ilma, additional, Colon-Ortiz, Pedro, additional, Colón-Hernández, Pedro J., additional, Carrasquillo-Navarro, Orlando J., additional, Carrasquillo, Merari, additional, Vazquez, Nivea, additional, Sosa-Padilla, Miguel, additional, Cintron-Pinero, Alex, additional, Ayala, Mayra, additional, Pacheco, Olga, additional, Rivera, Catalina, additional, Sotomayor-Gonzalez, Irma, additional, Claudio, Jamie, additional, Lazaro, Jose, additional, Arce, Migdalia, additional, Heres, Lourdes, additional, Perez, Alba, additional, Tavarez-Valle, Jose, additional, Arocho, Ferlinda, additional, Torres, Mercedes, additional, Vazquez, Melvaliz, additional, Aurigemma, Gerard P., additional, Takis-Smith, Rebecca, additional, Andrieni, Julia, additional, Bodkin, Noelle, additional, Chaudhary, Kiran, additional, Hu, Paula, additional, Kostis, John, additional, Cosgrove, Nora, additional, Bankowski, Denise, additional, Boleyn, Monica, additional, Casazza, Laurie, additional, Giresi, Victoria, additional, Patel, Tosha, additional, Squindo, Erin, additional, Wu, Yan, additional, Henson, Zeb, additional, Wofford, Marion, additional, Lowery, Jessica, additional, Minor, Deborah, additional, Harkins, Kimberley, additional, Auchus, Alexander, additional, Flessner, Michael, additional, Adair, Cathy, additional, Asher, Jordan, additional, Loope, Debbie, additional, Cobb, Rita, additional, Venegas, Reiner, additional, Bigger, Thomas, additional, Bello, Natalie, additional, Homma, Shunichi, additional, Donovan, Daniel, additional, Lopez-Jimenez, Carlos, additional, Tirado, Amilcar, additional, Getaneh, Asqual, additional, Tang, Rocky, additional, Durant, Sabrina, additional, Maurer, Mathew, additional, Teruya, Sergio, additional, Helmke, Stephen, additional, Alvarez, Julissa, additional, Campbell, Ruth, additional, Pisoni, Roberto, additional, Sturdivant, Rachel, additional, Brooks, Deborah, additional, Counts, Caroline, additional, Hunt, Vickie, additional, Spillers, Lori, additional, Brautigam, Donald, additional, Kitchen, Timothy, additional, Gorman, Timothy, additional, Sayers, Jessica, additional, Button, Sarah, additional, Chiarot, June, additional, Fischer, Rosemary, additional, Lyon, Melissa, additional, Resnick, Maria, additional, Hodges, Nicole, additional, Ferreira, Jennifer, additional, Cushman, William, additional, Wall, Barry, additional, Nichols, Linda, additional, Burns, Robert, additional, Martindale-Adams, Jennifer, additional, Berlowitz, Dan, additional, Clark, Elizabeth, additional, Walsh, Sandy, additional, Geraci, Terry, additional, Huff, Carol, additional, Shaw, Linda, additional, Servilla, Karen, additional, Vigil, Darlene, additional, Barrett, Terry, additional, Sweeney, Mary Ellen, additional, Johnson, Rebecca, additional, McConnell, Susan, additional, Salles, Khadijeh Shahid, additional, Watson, Francoise, additional, Schenk, Cheryl, additional, Whittington, Laura, additional, Maher, Maxine, additional, Williams, Jonathan, additional, Swartz, Stephen, additional, Conlin, Paul, additional, Alexis, George, additional, Lamkin, Rebecca, additional, Underwood, Patti, additional, Gomes, Helen, additional, Rosendorff, Clive, additional, Atlas, Stephen, additional, Khan, Saadat, additional, Gonzalez, Waddy, additional, Barcham, Samih, additional, Kwon, Lawrence, additional, Matar, Matar, additional, Adhami, Anwar, additional, Basile, Jan, additional, John, Joseph, additional, Ham, Deborah, additional, Baig, Hadi, additional, Saklayen, Mohammed, additional, Yap, Jason, additional, Neff, Helen, additional, Miller, Carol, additional, Zheng-Phelan, Ling, additional, Gappy, Saib, additional, Rau, Shiva, additional, Raman, Arathi, additional, Berchou, Vicki, additional, Jones, Elizabeth, additional, Olgren, Erin, additional, Marbury, Cynthia, additional, Yudd, Michael, additional, Sastrasinh, Sithiporn, additional, Michaud, Jennine, additional, Fiore, Jessica, additional, Kutza, Marianne, additional, Shorr, Ronald, additional, Mount, Rattana, additional, Dunn, Helen, additional, Stinson, Susan, additional, Hunter, Jessica, additional, Taylor, Addison, additional, Bates, Jeffery, additional, Anderson, Catherine, additional, Kirchner, Kent, additional, Stubbs, Jodi, additional, Hinton, Ardell, additional, Spencer, Anita, additional, Sharma, Santosh, additional, Wiegmann, Thomas, additional, Mehta, Smita, additional, Krause, Michelle, additional, Dishongh, Kate, additional, Childress, Richard, additional, Gyamlani, Geeta, additional, Niakan, Atossa, additional, Thompson, Cathy, additional, Moody, Janelle, additional, Gresham, Carolyn, additional, Whittle, Jeffrey, additional, Barnas, Gary, additional, Wolfgram, Dawn, additional, Cortese, Heidi, additional, Johnson, Jonette, additional, Roumie, Christianne, additional, Hung, Adriana, additional, Wharton, Jennifer, additional, Niesner, Kurt, additional, Katz, Lois, additional, Richardson, Elizabeth, additional, Brock, George, additional, Holland, Joanne, additional, Dixon, Troy, additional, Zias, Athena, additional, Spiller, Christine, additional, Baker, Penelope, additional, Felicetta, James, additional, Rehman, Shakaib, additional, Bingham, Kelli, additional, Watnick, Suzanne, additional, Cohen, David, additional, Weiss, Jessica, additional, Johnston, Tera, additional, Giddings, Stephen, additional, Yamout, Hala, additional, Klein, Andrew, additional, Rowe, Caroline, additional, Vargo, Kristin, additional, Waidmann, Kristi, additional, Papademetriou, Vasilios, additional, Elkhoury, Jean Pierre, additional, Gregory, Barbara, additional, Amodeo, Susan, additional, Bloom, Mary, additional, Goldfarb-Waysman, Dalia, additional, Treger, Richard, additional, Kashefi, Mehran, additional, Huang, Christina, additional, Knibloe, Karen, additional, Ishani, Areef, additional, Slinin, Yelena, additional, Olney, Christine, additional, Rust, Jacqueline, additional, Fanti, Paolo, additional, Dyer, Christopher, additional, Bansal, Shweta, additional, Dunnam, Monica, additional, Hu, Lih-Lan, additional, and Zarate-Abbott, Perla, additional

Published
2022
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27. Cetylpyridinium chloride is a potent AMP-activated kinase (AMPK) inducer and has therapeutic potential in cancer

Author

Sonia A. Allen, James M. Angelastro, Alexey Tomilov, Thomas K. Sears, Sandipan Datta, Gino A Cortopassi, Kevin D. Woolard, and Jose Sandoval

Subjects
0301 basic medicine, Cell Survival, Antineoplastic Agents, Cetylpyridinium, Pharmacology, Cetylpyridinium chloride, Cell Line, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, AMP-activated protein kinase, medicine, Animals, Humans, Inducer, Protein kinase A, Molecular Biology, biology, Adenylate Kinase, Cancer, AMPK, Glioma, Cell Biology, medicine.disease, Metformin, 030104 developmental biology, chemistry, Mitochondrial biogenesis, Anti-Infective Agents, Local, Hepatocytes, Neoplastic Stem Cells, biology.protein, Molecular Medicine, 030217 neurology & neurosurgery, medicine.drug
Abstract

AMP-activated protein kinase (AMPK) is a eukaryotic energy sensor and protector from mitochondrial/energetic stress that is also a therapeutic target for cancer and metabolic disease. Metformin is an AMPK inducer that has been used in cancer therapeutic trials. Through screening we isolated cetylpyridinium chloride (CPC), a drug known to dose-dependently inhibit mitochondrial complex 1, as a potent and dose-dependent AMPK stimulator. Mitochondrial biogenesis and bioenergetics changes have also been implicated in glioblastoma, which is the most aggressive form of brain tumors. Cetylpyridinium chloride has been administered in humans as a safe drug-disinfectant for several decades, and we report here that under in vitro conditions, cetylpyridinium chloride kills glioblastoma cells in a dose dependent manner at a higher efficacy compared to current standard of care drug, temozolomide.

Published
2020
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28. Sensitivity of a bedside reagent strip for the detection of spontaneous bacterial peritonitis in ED patients with ascites

Author

Gregory W. Hendey, Robert E. Woolard, Radosveta N. Wells, Deena I. Bengiamin, Daniel Vo, Rene Ramirez, Leann Mainis, Scott B. Crawford, and Brian Chinnock

Subjects
Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, Peritonitis, Gastroenterology, Spontaneous bacterial peritonitis, Predictive Value of Tests, Internal medicine, Ascites, medicine, Paracentesis, Ascitic Fluid, Humans, Prospective Studies, Reagent Strips, medicine.diagnostic_test, business.industry, Peritoneal fluid, Bacterial Infections, General Medicine, Middle Aged, medicine.disease, Confidence interval, Leukocyte esterase, Point-of-Care Testing, Case-Control Studies, Emergency Medicine, Female, medicine.symptom, business
Abstract

Study objective To determine the sensitivity of a highly sensitive bedside leukocyte esterase reagent strip (RS) for detection of spontaneous bacterial peritonitis (SBP) in emergency department (ED) ascites patients undergoing paracentesis. Methods We conducted a prospective, observational cohort study of ED ascites patients undergoing paracentesis at two academic facilities. Two practitioners, blinded to each other's results, did a bedside RS analysis of the peritoneal fluid in each patient and documented the RS reading at 3-min according to manufacturer-specified colorimetric strip reading as either “negative”, “trace”, “small”, or “large”. The primary outcome measure was sensitivity of the RS strip for SBP (absolute neutrophil count ≥ 250 cells/mm3) at the “trace” threshold (positive equals trace or greater). Results There were 330 cases enrolled, with 635 fluid analyses performed. Of these, 40 fluid samples had SBP (6%). Bedside RS had a sensitivity, specificity, positive predictive value, and negative predictive value of 95% (95% CI 82%–99%), 48% (95% CI 44%–52%), 11% (95% CI 10%–11%), and 99% (95% CI 97%–99%) respectively at the “trace” threshold for the detection of SBP. Conclusion Bedside use of the RS in ED ascites patients demonstrated high sensitivity for SBP. Given the wide confidence intervals, we cannot currently recommend it as a stand-alone test. We recommend further study with a larger number of SBP patients, potentially combining a negative RS result with low clinical suspicion to effectively rule out SBP without formal laboratory analysis.

Published
2019
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32. Macrophage CD14 impacts immune defenses against influenza virus in allergic hosts

Author

Kim S. LeMessurier, Amali E. Samarasinghe, Maneesha Palipane, Anna K. Schofield, Stacie Woolard, and John D. Snyder

Subjects
0301 basic medicine, Viral pathogenesis, CD14, 030106 microbiology, Lipopolysaccharide Receptors, Inflammation, Real-Time Polymerase Chain Reaction, Microbiology, Article, Virus, Mice, 03 medical and health sciences, Immune system, Orthomyxoviridae Infections, medicine, Animals, Asthma, Mice, Knockout, Innate immune system, Histocytochemistry, business.industry, Macrophages, Body Weight, Viral Load, Flow Cytometry, Orthomyxoviridae, medicine.disease, respiratory tract diseases, Disease Models, Animal, 030104 developmental biology, Infectious Diseases, Immunology, medicine.symptom, business, Viral load
Abstract

Asthma and influenza are leading causes of worldwide morbidity and mortality. Although these two conditions can co-exist in the same patient, the immune parameters that impact disease outcomes are not fully elucidated. The importance of macrophages to both conditions suggested a role for CD14, a co-receptor for endotoxin, as a regulatory mechanism for innate immune responses during asthma and influenza co-morbidity. Herein, we hypothesized that parameters of influenza morbidity will be reduced in the absence of CD14. Age and gender matched wild-type (WT) and CD14 knock-out (KO) mice were subjected to our validated model of Aspergillus-induced model of asthma and/or influenza. Characteristics of disease pathogenesis were investigated using standard methods in weight loss, flow cytometry, airway resistance, histology, quantitative real-time PCR, and viral titer quantification. The absence of CD14 did not have an impact on morbidity as these mice were equally susceptible to disease with similar airway resistance. Peribronchovascular inflammation and goblet cell content were equivalent between WT and KO mice in asthma alone and asthma and influenza co-morbidity. Co-morbid KO mice had less lymphocytes and eosinophils in the airways although their lung viral burden was equivalent to WT. Inflammatory gene signatures were altered in co-morbid mice in each genotype. CD14 expression on macrophages is necessary for airway inflammation but not for viral pathogenesis in allergic hosts.

Published
2019
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33. AAV8-mediated overexpression of mPCSK9 in liver differs between male and female mice

Author

Aimee E. Vozenilek, Sunitha Chandran, Robert M. Schilke, Ronald Klein, Reneau Castore, Matthew D. Woolard, and Cassidy M.R. Blackburn

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, Hypercholesterolemia, 030204 cardiovascular system & hematology, Biology, Article, Viral vector, law.invention, Mice, 03 medical and health sciences, Transduction (genetics), chemistry.chemical_compound, Sex Factors, 0302 clinical medicine, law, Internal medicine, medicine, Animals, Cholesterol, PCSK9, Gene Transfer Techniques, Dependovirus, Proprotein convertase, Phenotype, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, Endocrinology, Liver, chemistry, Mutation, Recombinant DNA, Kexin, Female, Proprotein Convertase 9, Cardiology and Cardiovascular Medicine
Abstract

Abstrat Background and aims The recombinant adeno-associated viral vector serotype 8 expressing the gain-of-function mutation of mouse proprotein convertase subtilisin/kexin type 9 (AAV8- PCSK9) is a new model for the induction of hypercholesterolemia. AAV8 preferentially infects hepatocytes and the incorporated liver-specific promoter should ensure expression of PCSK9 in the liver. Since tissue distribution of AAVs can differ between male and female mice, we investigated the differences in PCSK9 expression and hypercholesterolemia development between male and female mice using the AAV8-PCSK9 model. Methods Male and female C57BL/6 mice were injected with either a low-dose or high-dose of AAV8-PCSK9 and fed a high-fat diet. Plasma lipid levels were evaluated as a measure of the induction of hypercholesterolemia. Results Injection of mice with low dose AAV8-PCSK9 dramatically elevated both serum PCSK9 and cholesterol levels in male but not female mice. Increasing the dose of AAV8-PCSK9 threefold in female mice rescued the hypercholesterolemia phenotype but did not result in full restoration of AAV8-PCSK9 transduction of livers in female mice compared to the low-dose male mice. Our data demonstrate female mice respond differently to AAV8-PCSK9 injection compared to male mice. Conclusions These differences do not hinder the use of female mice when AAV8-PCSK9 doses are taken into consideration. However, localization to and production of AAV8-PCSK9 in organs besides the liver in mice may introduce confounding factors into studies and should be considered during experimental design.

Published
2018
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34. IL-1β reduces cardiac lymphatic muscle contraction via COX-2 and PGE2 induction: Potential role in myocarditis

Author

Ikuo Tsunoda, Mariappan Muthuchamy, Felicity N. E. Gavins, Mohamed Ghoweba, Pierre Yves Von der Weid, Felix Becker, Mahmoud Al-Kofahi, Yuping Wang, Seiichi Omura, Anatoliy A. Gashev, Israa Shihab, Christopher B. Pattillo, Fumitaka Sato, David C. Zawieja, J. Steven Alexander, and Matthew D. Woolard

Subjects
0301 basic medicine, Pharmacology, Anakinra, Myocarditis, business.industry, medicine.drug_class, EP4 Receptor, Prostaglandin, General Medicine, 030204 cardiovascular system & hematology, Receptor antagonist, medicine.disease, Contractility, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, Lymphatic system, chemistry, Medicine, Tumor necrosis factor alpha, business, medicine.drug
Abstract

The role of lymphatic vessels in myocarditis is largely unknown, while it has been shown to play a key role in other inflammatory diseases. We aimed to investigate the role of lymphatic vessels in myocarditis using in vivo model induced with Theiler's murine encephalomyelitis virus (TMEV) and in vitro model with rat cardiac lymphatic muscle cells (RCLMC). In the TMEV model, we found that upregulation of a set of inflammatory mediator genes, including interleukin (IL)-1β, tumor necrosis factor (TNF)-αand COX-2 were associated with disease activity. Thus, using in vitro collagen gel contraction assays, we decided to clarify the role(s) of these mediators by testing contractility of RCLMC in response to IL-1β and TNF-α individually and in combination, in the presence or absence of: IL-1 receptor antagonist (Anakinra); cyclooxygenase (COX) inhibitors inhibitors (TFAP, diclofenac and DuP-697). IL-1β impaired RCLMC contractility dose-dependently, while co-incubation with both IL-1β and TNF-α exhibited synergistic effects in decreasing RCLMC contractility with increased COX-2 expression. Anakinra maintained RCLMC contractility; Anakinra blocked the mobilization of COX-2 induced by IL-1β with or without TNF-α. COX-2 inhibition blocked the IL-1β-mediated decrease in RCLMC contractility. Mechanistically, we found that IL-1β increased prostaglandin (PG) E2 release dose-dependently, while Anakinra blocked IL-1β mediated PGE2 release. Using prostaglandin E receptor 4 (EP4) receptor antagonist, we demonstrated that EP4 receptor blockade maintained RCLMC contractility following IL-1β exposure. Our results indicate that IL-1β reduces RCLMC contractility via COX-2/PGE2 signaling with synergistic cooperation by TNF-α. These pathways may help provoke inflammatory mediator accumulation within the heart, driving progression from acute myocarditis into dilated cardiomyopathy.

Published
2018
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35. Investigating the use of multi-point coupling for single-sensor bearing estimation in one direction

Author

Americo G. Woolard, Austin A. Phoenix, and Pablo A. Tarazaga

Subjects
010302 applied physics, Physics, Acoustics and Ultrasonics, Mechanical Engineering, Acoustics, Stiffness, 02 engineering and technology, Impulse (physics), 021001 nanoscience & nanotechnology, Condensed Matter Physics, 01 natural sciences, Mechanics of Materials, 0103 physical sciences, medicine, medicine.symptom, 0210 nano-technology, Large diameter, Multi point
Abstract

Bearing estimation of radially propagating symmetric waves in solid structures typically requires a minimum of two sensors. As a test specimen, this research investigates the use of multi-point coupling to provide directional inference using a single-sensor. By this provision, the number of sensors required for localization can be reduced. A finite-element model of a beam is constructed with a symmetrically placed bipod that has asymmetric joint-stiffness properties. Impulse loading is applied at different points along the beam, and measurements are taken from the apex of the bipod. A technique is developed to determine the direction-of-arrival of the propagating wave. The accuracy when using the bipod with the developed technique is compared against results gathered without the bipod and measuring from an asymmetric location along the beam. The results show 92% accuracy when the bipod is used, compared to 75% when measuring without the bipod from an asymmetric location. A geometry investigation finds the best accuracy results when one leg of the bipod has a low stiffness and a large diameter relative to the other leg.

Published
2018
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36. Amine-functionalized fumed silica for CO2 capture through particle molecular layer deposition

Author

Annika Lai, Alan W. Weimer, Hailey C. Loehde-Woolard, Jessica Burger, Robert Pfeffer, and W. Wilson McNeary

Subjects
Sorbent, Materials science, Applied Mathematics, General Chemical Engineering, General Chemistry, TMPTA, Industrial and Manufacturing Engineering, chemistry.chemical_compound, Adsorption, chemistry, Chemical engineering, Triethoxysilane, Particle, Amine gas treating, Layer (electronics), Fumed silica
Abstract

Solid adsorbent materials for CO2 capture have received increasing attention due to the high regenerative energy requirements and physical limitations of traditional liquid systems. Supported amines have become widely-researched materials due to their ambient adsorption capabilities and low regeneration temperatures. Here, Particle Molecular Layer Deposition (MLD) is introduced as a novel loading method for amine functionalization to improve the regeneration stability and adsorption capacity of supported amine sorbents. This paper confirms two MLD chemistries: (3-aminopropyl)triethoxysilane (APTES) and N1-(3-trimethoxysilylpropyl)diethylene triamine (TMPTA). Both precursors were deposited at 150 °C in a binary reaction with water. Adsorption capacity of the amine functional groups increased to ~0.005 mmol/m2 as the number of MLD cycles increased. Low sorbent regeneration temperatures and stable regeneration of active sites over 25 cycles were demonstrated by both the APTES and TMPTA functionalized sorbent. This is the first demonstration of an MLD process used to functionalize a sorbent for CO2 capture. This is also the first use of TMPTA for MLD.

Published
2021
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38. Effects of intensive versus standard blood pressure control on domain-specific cognitive function: a substudy of the SPRINT randomised controlled trial

Author

Rapp, Stephen R, primary, Gaussoin, Sarah A, additional, Sachs, Bonnie C, additional, Chelune, Gordon, additional, Supiano, Mark A, additional, Lerner, Alan J, additional, Wadley, Virginia G, additional, Wilson, Valarie M, additional, Fine, Lawrence J, additional, Whittle, Jeff C, additional, Auchus, Alexander P, additional, Beddhu, Srinivasan, additional, Berlowitz, Dan R, additional, Bress, Adam P, additional, Johnson, Karen C, additional, Krousel-Wood, Marie, additional, Martindale-Adams, Jennifer, additional, Miller, Eliza C, additional, Rifkin, Dena E, additional, Snyder, Joni K, additional, Tamariz, Leonardo, additional, Wolfgram, Dawn F, additional, Cleveland, Maryjo L, additional, Yang, Mia, additional, Nichols, Linda O, additional, Bryan, Robert Nick, additional, Reboussin, David M, additional, Williamson, Jeff D, additional, Pajewski, Nicholas M, additional, Rapp, Stephen R, additional, Cheung, Alfred K, additional, Coker, Laura H, additional, Crowe, Michael G, additional, Cushman, William C, additional, Cutler, Jeffery A, additional, Davatzikos, Christos, additional, Desiderio, Lisa, additional, Doshi, Jimit, additional, Erus, Guray, additional, Harris, Darrin, additional, Kimmel, Paul L, additional, Tamura, Manjula K, additional, Launer, Lenore J, additional, Lewis, Cora E, additional, Moy, Claudia S, additional, Oparil, Suzanne, additional, Ogrocki, Paula K, additional, Rahman, Mahboob, additional, Nasrallah, Ilya M, additional, Rocco, Michael V, additional, Sink, Kaycee M, additional, Still, Carolyn H, additional, Walker, Jennifer, additional, Weiner, Daniel E, additional, Whelton, Paul K, additional, Wilson, Valerie M, additional, Woolard, Nancy, additional, Wright, Jackson T, additional, Wright, Clinton B, additional, and Bryan, R Nick, additional

Published
2020
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41. INSPIRE: A European training network to foster research and training in cardiovascular safety pharmacology

Author

Guns, Pieter-Jan D., primary, Guth, Brian D., additional, Braam, Stefan, additional, Kosmidis, Georgios, additional, Matsa, Elena, additional, Delaunois, Annie, additional, Gryshkova, Vitalina, additional, Bernasconi, Sylvain, additional, Knot, Harm J., additional, Shemesh, Yair, additional, Chen, Alon, additional, Markert, Michael, additional, Fernández, Miguel A., additional, Lombardi, Damiano, additional, Grandmont, Céline, additional, Cillero-Pastor, Berta, additional, Heeren, Ron M.A., additional, Martinet, Wim, additional, Woolard, Jeanette, additional, Skinner, Matt, additional, Segers, Vincent F.M., additional, Franssen, Constantijn, additional, Van Craenenbroeck, Emeline M., additional, Volders, Paul G.A., additional, Pauwelyn, Thomas, additional, Braeken, Dries, additional, Yanez, Paz, additional, Correll, Krystle, additional, Yang, Xi, additional, Prior, Helen, additional, Kismihók, Gábor, additional, De Meyer, Guido R.Y., additional, and Valentin, Jean-Pierre, additional

Published
2020
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44. A monoclonal antibody raised against a thermo-stabilised β1-adrenoceptor interacts with extracellular loop 2 and acts as a negative allosteric modulator of a sub-set of β1-adrenoceptors expressed in stable cell lines

Author

Mark Soave, Catherine J Hutchings, Alastair J.H. Brown, G. Cseke, Jeanette Woolard, and Stephen J. Hill

Subjects
0301 basic medicine, Pharmacology, Allosteric modulator, medicine.drug_class, HEK 293 cells, Allosteric regulation, Plasma protein binding, Biology, Monoclonal antibody, Biochemistry, Molecular biology, 3. Good health, Cell biology, 03 medical and health sciences, 030104 developmental biology, medicine, Receptor, Peptide sequence, G protein-coupled receptor
Abstract

Recent interest has focused on antibodies that can discriminate between different receptor conformations. Here we have characterised the effect of a monoclonal antibody (mAb3), raised against a purified thermo-stabilised turkey β1-adrenoceptor (β1AR-m23 StaR), on β1-ARs expressed in CHO-K1 or HEK 293 cells. Immunohistochemical and radioligand-binding studies demonstrated that mAb3 was able to bind to ECL2 of the tβ1-AR, but not its human homologue. Specific binding of mAb3 to tβ1-AR was inhibited by a peptide based on the turkey, but not the human, ECL2 sequence. Studies with [3H]-CGP 12177 demonstrated that mAb3 prevented the binding of orthosteric ligands to a subset (circa 40%) of turkey β1-receptors expressed in both CHO K1 and HEK 293 cells. MAb3 significantly reduced the maximum specific binding capacity of [3H]-CGP-12177 without influencing its binding affinity. Substitution of ECL2 of tβ1-AR with its human equivalent, or mutation of residues D186S, P187D, Q188E prevented the inhibition of [3H]-CGP 12177 binding by mAb3. MAb3 also elicited a negative allosteric effect on agonist-stimulated cAMP responses. The identity of the subset of turkey β1-adrenoceptors influenced by mAb3 remains to be established but mAb3 should become an important tool to investigate the nature of β1-AR conformational states and oligomeric complexes.

Published
2018
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45. Impacts of maternal diet and exercise on offspring behavior and body weights

Author

Katherine L. McDaniel, Jason N. Franklin, Emily Alice Woolard, Virginia C. Moser, Pamela M. Phillips, and Christopher J. Gordon

Subjects
0301 basic medicine, Litter (animal), medicine.medical_specialty, Offspring, Morris water navigation task, Weaning, Biology, Diet, High-Fat, Toxicology, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, food, Developmental Neuroscience, Pregnancy, Internal medicine, Lactation, medicine, Animals, Rats, Long-Evans, Obesity, Behavior, Animal, Body Weight, medicine.disease, food.food, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, Prenatal Exposure Delayed Effects, Chocolate milk, Female, 030217 neurology & neurosurgery
Abstract

Human and animal studies indicate that maternal obesity can negatively impact aspects of metabolism and neurodevelopment in the offspring. Not known, however, is whether maternal exercise can alter these adverse outcomes. In this study, Long-Evans female rats were provided a high fat (60%; HFD) or control diet (CD) 44days before mating and throughout gestation and lactation. Running wheels were available to half of each diet group during the gestational period only, resulting in four conditions: CD diet with (CDRW) or without (sedentary; CDSED) exercise, and HFD with (HFRW) or without (HFSED) exercise. Only male offspring (one per litter) were available for this study: they were put on control diet two weeks after weaning and examined using behavioral evaluations up to four months of age. Before weaning, offspring of CDRW dams weighed less than offspring from CDSED or HFD dams. After weaning, the lower weight in CDRW offspring generally persisted. Adult offspring from HFSED dams performed worse than the HFRW group in a Morris water maze during initial spatial training as well as reversal learning; memory was not impacted. No differences between groups were seen in tests of novel object recognition, social approach, or chocolate milk preference. Thus, maternal diet and exercise produced differential effects on body weights and cognitive behaviors in the offspring, and the data demonstrate a positive impact of maternal exercise on the offspring in that it ameliorated some deleterious behavioral effects of a maternal high fat diet.

Published
2017
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46. Toll-like receptors in the pathogenesis of pulmonary fibrosis

Author

Theodoros Karampitsakos, Demosthenes Bouros, Tony Woolard, and Argyris Tzouvelekis

Subjects
0301 basic medicine, Pulmonary Fibrosis, Lung Disorder, 03 medical and health sciences, Idiopathic pulmonary fibrosis, 0302 clinical medicine, Immune system, Fibrosis, Pulmonary fibrosis, medicine, Animals, Humans, Pharmacology, Wound Healing, Lung, business.industry, Toll-Like Receptors, Pattern recognition receptor, respiratory system, medicine.disease, Acquired immune system, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Immunology, business, Signal Transduction
Abstract

Pulmonary fibrosis (PF) constitutes the end stage of a broad range of heterogeneous interstitial lung diseases, characterized by the destruction of the pulmonary parenchyma, deposition of extracellular matrix and dramatic changes in the phenotype of both fibroblasts and alveolar epithelial cells. More than 200 causes of pulmonary fibrosis have been identified so far, yet the most common form is idiopathic pulmonary fibrosis (IPF). IPF is a lethal lung disorder of unknown etiology with a gradually increasing worldwide incidence and a median survival of 3-5 years from the time of diagnosis. Despite intense research efforts, the pathogenesis remains elusive and no effective treatment is available. Accumulating body of evidence suggests an abnormal wound healing response followed by extracellular matrix deposition, destruction of lung architecture, ultimately leading to respiratory failure. The contribution of immune system in lung fibrogenesis had been largely underscored due to the absence of response to immunosuppressive agents; however, the premise that lung fibrosis has an immunologic background has been recently revived. Toll-like receptors (TLRs) are pattern recognition receptors (PRRs), which link innate and adaptive immune response and regulate wound healing. TLRs promote tissue repair or fibrosis in many disease settings including lung fibrosis, albeit with profound differences depending on the cellular microenvironment. This review summarizes the current state of knowledge regarding the mechanistic implications between TLRs and lung fibrosis and highlights the therapeutic potential of targeting TLR signaling at the ligand or receptor level.

Published
2017
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47. Real-time analysis of the binding of fluorescent VEGF 165 a to VEGFR2 in living cells: Effect of receptor tyrosine kinase inhibitors and fate of internalized agonist-receptor complexes

Author

Thomas Machleidt, Amanda J. Wheal, Matthew B. Robers, Diana C Alcobia, Stephen J. Hill, Stephen J. Briddon, Jeanette Woolard, Kristin M. Riching, Keith V. Wood, Kris Zimmerman, Chloe J. Peach, Laura E. Kilpatrick, and Rachel Friedman-Ohana

Subjects
0301 basic medicine, Pharmacology, Agonist, medicine.drug_class, Endosome, media_common.quotation_subject, Kinase insert domain receptor, Endocytosis, 7. Clean energy, Biochemistry, 3. Good health, Cell biology, Vascular endothelial growth factor, 03 medical and health sciences, chemistry.chemical_compound, Vascular endothelial growth factor A, 030104 developmental biology, chemistry, cardiovascular system, medicine, Receptor, Internalization, media_common
Abstract

Vascular endothelial growth factor (VEGF) is an important mediator of angiogenesis. Here we have used a novel stoichiometric protein-labeling method to generate a fluorescent variant of VEGF (VEGF165a-TMR) labeled on a single cysteine within each protomer of the antiparallel VEGF homodimer. VEGF165a-TMR has then been used in conjunction with full length VEGFR2, tagged with the bioluminescent protein NanoLuc, to undertake a real time quantitative evaluation of VEGFR2 binding characteristics in living cells using bioluminescence resonance energy transfer (BRET). This provided quantitative information on VEGF-VEGFR2 interactions. At longer incubation times, VEGFR2 is internalized by VEGF165a-TMR into intracellular endosomes. This internalization can be prevented by the receptor tyrosine kinase inhibitors (RTKIs) cediranib, sorafenib, pazopanib or vandetanib. In the absence of RTKIs, the BRET signal is decreased over time as a consequence of the dissociation of agonist from the receptor in intracellular endosomes and recycling of VEGFR2 back to the plasma membrane.

Published
2017
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48. Dynapenia and Metabolic Health in Obese and Nonobese Adults Aged 70 Years and Older: The LIFE Study

Author

Mylène Aubertin-Leheudre, Stephen Anton, Daniel P. Beavers, Todd M. Manini, Roger Fielding, Ann Newman, Tim Church, Stephen B. Kritchevsky, David Conroy, Mary M. McDermott, Anda Botoseneanu, Michelle E. Hauser, Marco Pahor, Thomas Gill, Carlos Fragoso, Jack M. Guralnik, Christiaan Leeuwenburgh, Connie Caudle, Lauren Crump, Latonia Holmes, Jocelyn Lee, Ching-ju Lu, Michael E. Miller, Mark A. Espeland, Walter T. Ambrosius, William Applegate, Robert P. Byington, Delilah Cook, Curt D. Furberg, Lea N. Harvin, Leora Henkin, Med John Hepler, Fang-Chi Hsu, Laura Lovato, Wesley Roberson, Julia Rushing, Scott Rushing, Cynthia L. Stowe, Michael P. Walkup, Don Hire, W. Jack Rejeski, Jeffrey A. Katula, Peter H. Brubaker, Shannon L. Mihalko, Janine M. Jennings, Evan C. Hadley, Sergei Romashkan, Kushang V. Patel, Denise Bonds, Bonnie Spring, Joshua Hauser, Diana Kerwin, Kathryn Domanchuk, Rex Graff, Alvito Rego, Timothy S. Church, Steven N. Blair, Valerie H. Myers, Ron Monce, Nathan E. Britt, Melissa Nauta Harris, Ami Parks McGucken, Ruben Rodarte, Heidi K. Millet, Catrine Tudor-Locke, Ben P. Butitta, Sheletta G. Donatto, Shannon H. Cocreham, Abby C. King, Cynthia M. Castro, William L. Haskell, Randall S. Stafford, Leslie A. Pruitt, Kathy Berra, Veronica Yank, Roger A. Fielding, Miriam E. Nelson, Sara C. Folta, Edward M. Phillips, Christine K. Liu, Erica C. McDavitt, Kieran F. Reid, Dylan R. Kirn, Evan P. Pasha, Won S. Kim, Vince E. Beard, Eleni X. Tsiroyannis, Cynthia Hau, Stephen D. Anton, Susan Nayfield, Thomas W. Buford, Michael Marsiske, Bhanuprasad D. Sandesara, Jeffrey D. Knaggs, Megan S. Lorow, William C. Marena, Irina Korytov, Holly L. Morris, Margo Fitch, Floris F. Singletary, Jackie Causer, Katie A. Radcliff, Anne B. Newman, Stephanie A. Studenski, Bret H. Goodpaster, Nancy W. Glynn, Oscar Lopez, Neelesh K. Nadkarni, Kathy Williams, Mark A. Newman, George Grove, Janet T. Bonk, Jennifer Rush, Piera Kost, Diane G. Ives, Anthony P. Marsh, Tina E. Brinkley, Jamehl S. Demons, Kaycee M. Sink, Kimberly Kennedy, Rachel Shertzer-Skinner, Abbie Wrights, Rose Fries, Deborah Barr, Thomas M. Gill, Robert S. Axtell, Susan S. Kashaf, Nathalie de Rekeneire, Joanne M. McGloin, Karen C. Wu, Denise M. Shepard, Barbara Fennelly, Lynne P. Iannone, Raeleen Mautner, Theresa Sweeney Barnett, Sean N. Halpin, Matthew J. Brennan, Julie A. Bugaj, Maria A. Zenoni, Bridget M. Mignosa, Jeff Williamson, Hugh C. Hendrie, Stephen R. Rapp, Joe Verghese, Nancy Woolard, Mark Espeland, Janine Jennings, Valerie K. Wilson, Carl J. Pepine, Mario Ariet, Eileen Handberg, Daniel Deluca, James Hill, Anita Szady, Geoffrey L. Chupp, Gail M. Flynn, John L. Hankinson, Carlos A. Vaz Fragoso, Erik J. Groessl, and Robert M. Kaplan

Subjects
Male, medicine.medical_specialty, Waist, Blood lipids, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, Lower risk, Article, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Humans, Muscle Strength, Obesity, General Nursing, Abdominal obesity, Aged, Aged, 80 and over, Metabolic Syndrome, business.industry, Health Policy, General Medicine, Odds ratio, medicine.disease, Endocrinology, Female, Waist Circumference, Geriatrics and Gerontology, Metabolic syndrome, medicine.symptom, business, Body mass index
Abstract

Objective The purpose of this study was to examine the relationship between dynapenia and metabolic risk factors in obese and nonobese older adults. Methods A total of 1453 men and women (age ≥70 years) from the Lifestyle Interventions and Independence for Elders (LIFE) Study were categorized as (1) nondynapenic/nonobese (NDYN-NO), (2) dynapenic/nonobese (DYN-NO), (3) nondynapenic/obese (NDYN-O), or (4) dynapenic/obese (DYN-O), based on muscle strength (Foundation for the National Institute of Health criteria) and body mass index. Dependent variables were blood lipids, fasting glucose, blood pressure, presence of at least 3 metabolic syndrome (MetS) criteria, and other chronic conditions. Results A significantly higher likelihood of having abdominal obesity criteria in NDYN-NO compared with DYN-NO groups (55.6 vs 45.1%, P ≤ .01) was observed. Waist circumference also was significantly higher in obese groups (DYN-O = 114.0 ± 12.9 and NDYN-O = 111.2 ± 13.1) than in nonobese (NDYN-NO = 93.1 ± 10.7 and DYN-NO = 92.2 ± 11.2, P ≤ .01); and higher in NDYN-O compared with DYN-O ( P = .008). Additionally, NDYN-O demonstrated higher diastolic blood pressure compared with DYN-O (70.9 ± 10.1 vs 67.7 ± 9.7, P ≤ .001). No significant differences were found across dynapenia and obesity status for all other metabolic components ( P > .05). The odds of having MetS or its individual components were similar in obese and nonobese, combined or not with dynapenia (nonsignificant odds ratio [95% confidence interval]). Conclusion Nonobese dynapenic older adults had fewer metabolic disease risk factors than nonobese and nondynapenic older adults. Moreover, among obese older adults, dynapenia was associated with lower risk of meeting MetS criteria for waist circumference and diastolic blood pressure. Additionally, the presence of dynapenia did not increase cardiometabolic disease risk in either obese or nonobese older adults.

Published
2017
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49. Monitoring Ligand-Induced Changes in Receptor Conformation with NanoBiT Conjugated Nanobodies

Author

Raimond Heukers, Jeanette Woolard, Stephen J. Hill, Stephen J. Briddon, Barrie Kellam, Martine J. Smit, and Mark Soave

Subjects
0303 health sciences, Chemistry, Ligand, HEK 293 cells, Allosteric regulation, Immunoglobulin domain, Protein tag, 03 medical and health sciences, Chemokine receptor, 0302 clinical medicine, 030220 oncology & carcinogenesis, Biophysics, Luciferase, Receptor, 030304 developmental biology
Abstract

SummaryCamelid single-domain antibody fragments (nanobodies) offer the specificity of an antibody in a single 15kDa immunoglobulin domain. Their small size allows for easy genetic manipulation of the nanobody sequence to incorporate protein tags, facilitating their use as biochemical probes. The nanobody VUN400, which recognises the second extracellular loop of the human CXCR4 chemokine receptor, was used as a probe to monitor specific CXCR4 conformations. VUN400 was fused via its C-terminus to the 11-amino acid HiBiT tag (VUN400-HiBiT) which complements to LgBiT protein, forming a full length functional NanoLuc luciferase. Here, complemented luminescence was used to detect VUN400-HiBiT binding to CXCR4 receptors expressed in living HEK293 cells. VUN400-HiBiT binding to CXCR4 could be prevented by orthosteric and allosteric ligands, allowing VUN400-HiBiT to be used as a probe to detect specific conformations of CXCR4. These data demonstrate that the high specificity offered by extracellular-targeted nanobodies can be utilised to probe receptor pharmacology.

Published
2020
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50. B-PO04-137 SOLUBLE ST-2 LEVELS ARE ELEVATED IN PATIENTS WITH ATRIAL FIBRILLATION

Author

Zoya Mohammad, Christopher G. Kevil, Parinita Dherange, Matthew D. Woolard, Paari Dominic, Megan N. Watts, Gopi K. Kolluru, and Sindhu Thevuthasan

Subjects
medicine.medical_specialty, business.industry, Physiology (medical), Internal medicine, Cardiology, medicine, In patient, Atrial fibrillation, Cardiology and Cardiovascular Medicine, business, medicine.disease
Published
2021
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