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5. Age‐related increase of CD38 directs osteoclastogenic potential of monocytic myeloid‐derived suppressor cells through mitochondrial dysfunction in male mice.

Author

Thiyagarajan, Ramkumar, Zhang, Lixia, Glover, Omar D., Kwack, Kyu Hwan, Ahmed, Sara, Murray, Emma, Yellapu, Nanda Kumar, Bard, Jonathan, Seldeen, Kenneth L., Rosario, Spencer R., Troen, Bruce R., and Kirkwood, Keith L.

Abstract

An aged immune system undergoes substantial changes where myelopoiesis dominates within the bone marrow. Monocytic‐MDSCs (M‐MDSCs) have been found to play an important role in osteoclastogenesis and bone resorption. In this study, we sought to provide a more comprehensive understanding of the osteoclastogenic potential of bone marrow M‐MDSCs during normal aging through transcriptomic and metabolic changes. Using young mature and aged mice, detailed immunophenotypic analyses of myeloid cells revealed that the M‐MDSCs were not increased in bone marrow, however M‐MDSCS were significantly expanded in peripheral tissues. Although aged mice exhibited a similar number of M‐MDSCs in bone marrow, these M‐MDSCs had significantly higher osteoclastogenic potential and greater demineralization activity. Intriguingly, osteoclast progenitors from aged bone marrow M‐MDSCs exhibited greater mitochondrial respiration rate and glucose metabolism. Further, transcriptomic analyses revealed the upregulation of mitochondrial oxidative phosphorylation and glucose metabolism genes. Interestingly, there was 8‐fold increase in Cd38 mRNA gene expression, consistent with the Mouse Aging Cell Atlas transcriptomic database, and confirmed by qRT‐PCR. CD38 regulates NAD+ availability, and 78c, a small molecule inhibitor of CD38, reduced the mitochondrial oxygen consumption rate and glucose metabolism and inhibited the osteoclastogenic potential of aged mice bone marrow‐derived M‐MDSCs. These results indicate that the age‐related increase in Cd38 expression in M‐MDSCs bias the transcriptome of M‐MDSCs towards osteoclastogenesis. This enhanced understanding of the mechanistic underpinnings of M‐MDSCs and their osteoclastogenesis during aging could lead to new therapeutic approaches for age‐related bone loss and promote healthy aging. [ABSTRACT FROM AUTHOR]

Published
2024
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13. Supplementary Figure 2 from Inactivation or Loss of TTP Promotes Invasion in Head and Neck Cancer via Transcript Stabilization and Secretion of MMP9, MMP2, and IL-6

Author

Van Tubergen, Elizabeth A., primary, Banerjee, Rajat, primary, Liu, Min, primary, Broek, Robert Vander, primary, Light, Emily, primary, Kuo, Shiuhyang, primary, Feinberg, Stephen E., primary, Willis, Amanda L., primary, Wolf, Gregory, primary, Carey, Thomas, primary, Bradford, Carol, primary, Prince, Mark, primary, Worden, Francis P., primary, Kirkwood, Keith L., primary, and D'Silva, Nisha J., primary

Published
2023
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14. Supplementary Figure 3 from Inactivation or Loss of TTP Promotes Invasion in Head and Neck Cancer via Transcript Stabilization and Secretion of MMP9, MMP2, and IL-6

Author

Van Tubergen, Elizabeth A., primary, Banerjee, Rajat, primary, Liu, Min, primary, Broek, Robert Vander, primary, Light, Emily, primary, Kuo, Shiuhyang, primary, Feinberg, Stephen E., primary, Willis, Amanda L., primary, Wolf, Gregory, primary, Carey, Thomas, primary, Bradford, Carol, primary, Prince, Mark, primary, Worden, Francis P., primary, Kirkwood, Keith L., primary, and D'Silva, Nisha J., primary

Published
2023
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15. Supplementary Figure 4 from Inactivation or Loss of TTP Promotes Invasion in Head and Neck Cancer via Transcript Stabilization and Secretion of MMP9, MMP2, and IL-6

Author

Van Tubergen, Elizabeth A., primary, Banerjee, Rajat, primary, Liu, Min, primary, Broek, Robert Vander, primary, Light, Emily, primary, Kuo, Shiuhyang, primary, Feinberg, Stephen E., primary, Willis, Amanda L., primary, Wolf, Gregory, primary, Carey, Thomas, primary, Bradford, Carol, primary, Prince, Mark, primary, Worden, Francis P., primary, Kirkwood, Keith L., primary, and D'Silva, Nisha J., primary

Published
2023
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16. Supplementary Figure 5 from Inactivation or Loss of TTP Promotes Invasion in Head and Neck Cancer via Transcript Stabilization and Secretion of MMP9, MMP2, and IL-6

Author

Van Tubergen, Elizabeth A., primary, Banerjee, Rajat, primary, Liu, Min, primary, Broek, Robert Vander, primary, Light, Emily, primary, Kuo, Shiuhyang, primary, Feinberg, Stephen E., primary, Willis, Amanda L., primary, Wolf, Gregory, primary, Carey, Thomas, primary, Bradford, Carol, primary, Prince, Mark, primary, Worden, Francis P., primary, Kirkwood, Keith L., primary, and D'Silva, Nisha J., primary

Published
2023
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17. Supplementary Methods, Table 1 from Inactivation or Loss of TTP Promotes Invasion in Head and Neck Cancer via Transcript Stabilization and Secretion of MMP9, MMP2, and IL-6

Author

Van Tubergen, Elizabeth A., primary, Banerjee, Rajat, primary, Liu, Min, primary, Broek, Robert Vander, primary, Light, Emily, primary, Kuo, Shiuhyang, primary, Feinberg, Stephen E., primary, Willis, Amanda L., primary, Wolf, Gregory, primary, Carey, Thomas, primary, Bradford, Carol, primary, Prince, Mark, primary, Worden, Francis P., primary, Kirkwood, Keith L., primary, and D'Silva, Nisha J., primary

Published
2023
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18. Supplementary Figure Legend from Inactivation or Loss of TTP Promotes Invasion in Head and Neck Cancer via Transcript Stabilization and Secretion of MMP9, MMP2, and IL-6

Author

Van Tubergen, Elizabeth A., primary, Banerjee, Rajat, primary, Liu, Min, primary, Broek, Robert Vander, primary, Light, Emily, primary, Kuo, Shiuhyang, primary, Feinberg, Stephen E., primary, Willis, Amanda L., primary, Wolf, Gregory, primary, Carey, Thomas, primary, Bradford, Carol, primary, Prince, Mark, primary, Worden, Francis P., primary, Kirkwood, Keith L., primary, and D'Silva, Nisha J., primary

Published
2023
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19. Supplementary Figure 6 from Inactivation or Loss of TTP Promotes Invasion in Head and Neck Cancer via Transcript Stabilization and Secretion of MMP9, MMP2, and IL-6

Author

Van Tubergen, Elizabeth A., primary, Banerjee, Rajat, primary, Liu, Min, primary, Broek, Robert Vander, primary, Light, Emily, primary, Kuo, Shiuhyang, primary, Feinberg, Stephen E., primary, Willis, Amanda L., primary, Wolf, Gregory, primary, Carey, Thomas, primary, Bradford, Carol, primary, Prince, Mark, primary, Worden, Francis P., primary, Kirkwood, Keith L., primary, and D'Silva, Nisha J., primary

Published
2023
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20. Supplementary Figure 1 from Inactivation or Loss of TTP Promotes Invasion in Head and Neck Cancer via Transcript Stabilization and Secretion of MMP9, MMP2, and IL-6

Author

Van Tubergen, Elizabeth A., primary, Banerjee, Rajat, primary, Liu, Min, primary, Broek, Robert Vander, primary, Light, Emily, primary, Kuo, Shiuhyang, primary, Feinberg, Stephen E., primary, Willis, Amanda L., primary, Wolf, Gregory, primary, Carey, Thomas, primary, Bradford, Carol, primary, Prince, Mark, primary, Worden, Francis P., primary, Kirkwood, Keith L., primary, and D'Silva, Nisha J., primary

Published
2023
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24. Editorial: Early and accurate diagnosis and regulatory mechanism of lymph node metastasis in head and neck carcinoma.

Author

Fa-yu Liu, Kirkwood, Keith L., and Zhien Feng

Subjects
LYMPHATIC metastasis, THYROID cancer, EARLY diagnosis, HEAD & neck cancer, CARCINOMA, NECK, PROGNOSIS
Abstract

This article, published in Frontiers in Oncology, discusses the importance of early and accurate diagnosis of lymph node metastasis (LNM) in head and neck carcinoma. The authors highlight the limitations of current monitoring techniques, such as ultrasound, MRI, CT, and PET-CT, which rely on physician judgment and can result in inconsistent diagnoses. The article explores the use of radiomics and deep learning, branches of artificial intelligence, as potential solutions for more accurate and non-invasive diagnosis. The authors also present several studies that focus on the relationship between LNM and distant metastasis-free survival in different types of head and neck cancer. Overall, the article emphasizes the potential of medical imaging-based research methods to improve diagnostic accuracy and treatment decisions in head and neck carcinoma. [Extracted from the article]

Published
2024
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26. Periodontal disease is associated with increased gut colonization of pathogenic Haemophilus parainfluenzae in patients with Crohn’s disease

Author

Sohn, Jiho, primary, Li, Lu, additional, Zhang, Lixia, additional, Genco, Robert J., additional, Falkner, Karen L., additional, Tettelin, Hervé, additional, Rowsam, Aryn M., additional, Smiraglia, Dominic J., additional, Novak, Jan M., additional, Diaz, Patricia I., additional, Sun, Yijun, additional, and Kirkwood, Keith L., additional

Published
2023
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28. Tristetraprolin limits age-related expansion of myeloid-derived suppressor cells

Author

Kwack, Kyu Hwan, primary, Zhang, Lixia, additional, Kramer, Elliot D., additional, Thiyagarajan, Ramkumar, additional, Lamb, Natalie A., additional, Arao, Yukitomo, additional, Bard, Jonathan E., additional, Seldeen, Kenneth L., additional, Troen, Bruce R., additional, Blackshear, Perry J., additional, Abrams, Scott I., additional, and Kirkwood, Keith L., additional

Published
2022
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37. Porphyromonas gingivalis indirectly elicits intestinal inflammation by altering the gut microbiota and disrupting epithelial barrier function through IL9‐producing CD4 + T cells

Author

Sohn, Jiho, primary, Li, Lu, additional, Zhang, Lixia, additional, Settem, Rajendra P., additional, Honma, Kiyonobu, additional, Sharma, Ashu, additional, Falkner, Karen L., additional, Novak, Jan M., additional, Sun, Yijun, additional, and Kirkwood, Keith L., additional

Published
2022
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45. Contributors

Author

Abt, Elliot, primary, Aguirre, Alfredo, additional, Allen, Edward P., additional, Ammons, William F., additional, Anderson, Maxwell H., additional, Aoki, Akira, additional, Azzi, Robert R., additional, Bauer, Janet G., additional, Beumer, John, additional, Bloom, Mitchell J., additional, Serhal, Charbel Bou, additional, Bulkacz, Jaime, additional, Butler, Bobby, additional, Camargo, Paulo M., additional, Carranza, Fermin A., additional, Chang, Ting-Ling, additional, Cho, Sang-Choon, additional, Chou, Chih-Hung, additional, Ciancio, Sebastian G., additional, Cochran, David L., additional, Cooney, Joseph P., additional, Crall, James J., additional, Cross, J. David, additional, Dadamio, Jesica, additional, Derycke, Raymond R., additional, Diehl, Scott R., additional, Duperon, Donald F., additional, Elian, Nicolas, additional, Etienne, Daniel H., additional, Fazio, Robert C., additional, Fiorellini, Joseph P., additional, Forrest, Jane L., additional, Froum, Stuart J., additional, Froum, Scott H., additional, Gu, Ying, additional, Han, Thomas J., additional, Harrington, Gerald W., additional, Haytac, M. Cenk, additional, Hinrichs, James E., additional, Hogan, Eva L., additional, Huang, Ching-Yu, additional, Hujoel, Philippe P., additional, Ishikawa, Isao, additional, Jahn, Carol A., additional, Jakubovics, Nick, additional, Jolkovsky, David L., additional, Kamel, Brian P., additional, Kang, Mo K., additional, Kao, Daniel W.K., additional, Kenney, E. Barrie, additional, Kim, David, additional, Kim, Geon U., additional, Kirkwood, Keith L., additional, Klokkevold, Perry R., additional, Kokich, Vincent G., additional, Kuo, Fengshen, additional, Law, Clarice S., additional, Lieberman, Mark B., additional, Mariotti, Angelo, additional, McDevitt, Michael J., additional, McGregor, Adriana, additional, Mealey, Brian L., additional, Melnick, Philip R., additional, Merin, Robert L., additional, Miller, Syrene A., additional, Needleman, Ian, additional, Newman, Michael G., additional, Nevins, Marc L., additional, Nisengard, Russell J., additional, Novak, Karen F., additional, Novak, M. John, additional, Otomo-Corgel, Joan, additional, Ozcelik, Onur, additional, Park, Kwang-Bum, additional, Pattison, Anna Matsuishi, additional, Pattison, Gordon L., additional, Pelsmaekers, Birgit, additional, Perry, Dorothy A., additional, Preshaw, Philip, additional, Quirynen, Marc, additional, Rees, Terry D., additional, Reynolds, Mark A., additional, Rossa, Carlos, additional, Ryan, Maria Emanuel, additional, Scheyer, E. Todd, additional, Shanelec, Dennis A., additional, Shin, Kitetsu, additional, Shklar, Gerald, additional, Sims, Thomas N., additional, Spackman, Sue S., additional, Spear, Frank M., additional, Takei, Henry H., additional, Tapia, Jose Luis, additional, Tarnow, Dennis P., additional, Taylor, John J., additional, Tetradis, Sotirios, additional, Teughels, Wim, additional, Tibbetts, Leonard S., additional, Trabert, Kenneth C., additional, Urban, Istvan A., additional, Uzel, N. Buzin, additional, Van den Velde, Sandra, additional, Vendekerckhove, Betty, additional, Vercellotti, Tomaso, additional, Wada, Keisuke, additional, and Zackin, S. Jerome, additional

Published
2012
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48. Porphyromonas gingivalis indirectly elicits intestinal inflammation by altering the gut microbiota and disrupting epithelial barrier function through IL9‐producing CD4+ T cells.

Author

Sohn, Jiho, Li, Lu, Zhang, Lixia, Settem, Rajendra P., Honma, Kiyonobu, Sharma, Ashu, Falkner, Karen L., Novak, Jan M., Sun, Yijun, and Kirkwood, Keith L.

Abstract

Recent epidemiological studies have shown that inflammatory bowel disease is associated with periodontal disease. The oral–gut microbiota axis is a potential mechanism intersecting the two diseases. Porphyromonas gingivalis is currently considered a keystone oral pathogen involved in periodontal disease pathogenesis and disease progression. Recent studies have shown that oral ingestion of P. gingivalis leads to intestinal inflammation. However, the molecular underpinnings of P. gingivalis‐mediated gut inflammation have remained elusive. In this study, we show that the oral administration of P. gingivalis indeed leads to ileal inflammation and alteration in gut microbiota with significant reduction in bacterial alpha diversity despite the absence of P. gingivalis in the lower gastrointestinal tract. Utilizing an antibiotic‐conditioned mouse model, cecal microbiota transfer experiments were performed to demonstrate that P. gingivalis‐induced dysbiotic gut microbiota is sufficient to reproduce gut pathology. Furthermore, we observed a significant expansion in small intestinal lamina propria IL9+ CD4+ T cells, which was negatively correlated with both bacterial and fungal alpha diversity, signifying that P. gingivalis‐mediated intestinal inflammation may be due to the subsequent loss of gut microbial diversity. Finally, we detected changes in gene expression related to gut epithelial barrier function, showing the potential downstream effect of intestinal IL9+CD4+ T‐cell induction. This study for the first time showed the mechanism behind P. gingivalis‐mediated intestinal inflammation where P. gingivalis indirectly induces intestinal IL9+ CD4+ T cells and inflammation by altering the gut microbiota. Understanding the mechanism of P. gingivalis‐mediated intestinal inflammation may lead to the development of novel therapeutic approaches to alleviate the morbidity from inflammatory bowel disease patients with periodontal disease. [ABSTRACT FROM AUTHOR]

Published
2022
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50. Contributors

Author

Aguirre, Alfredo, Allen, Edward P., Alshagroud, Rana, Avila-Ortiz, Gustavo, Azzi, Robert R., Barsoum, Adam, Barwacz, Christopher A., Bassir, Seyed Hossein, Bergamini, Marco, Bezerra, Beatriz, Bickett, Lucy, Bloom, Mitchell J., Camargo, Paulo M., Carranza, Fermin A., Celenza, Frank, Periodontology, Cert, Orthodontics, Cert, Chambrone, Leandro, Chang, Ting-Ling, Chang, Yu-Cheng, Chao, Denny, Cho, Sang Choon, Patricia Chun, Yong-Hee, Dent, Med, Chung, Evelyn, Clark, Daniel R., Cobb, Charles M., Cochran, David L., Cooney, Joseph P., Crocket, Russell J., Cross, J. David, Dadamio, Jesica, Decker, Ann, Dekeyser, Christel, Diehl, Scott R., Divaris, Kimon, Do, Jonathan H., Dommisch, Henrik, Dragan, Irina F., Elangovan, Satheesh, Felix Gomez, Grace Gomez, Feres, Magda, Finkelman, Richard D., Fiorellini, Joseph P., Forrest, Jane L., Freire, Marcelo, Froum, Scott H., Froum, Stuart J., Ganesan, Sukirth M., Gidley, Mark David, Gu, Ying, Hajishengallis, George, Han, Thomas J., Haytac, M. Cenk, Hinrichs, James E., Holliday, Richard, Hujoel, Philippe P., Husain, Mohammed, Jahn, Carol A., Jakubovics, Nicholas S., John, Stephen, Kang, Mo K., Kantarci, Alpdogan, Kao, Richard T., Hernandez-Kapila, Yvonne L., Kebschull, Moritz, Kim, David M., Kirkwood, Keith L., Klokkevold, Perry R., Kokich, Vincent G., Korczeniewska, Olga A., Kotsakis, Georgios A., Kramer, Jill Marie, Kumar, Purnima S., Kuraji, Ryutaro, Lee, Chun-Teh, Li, Shuning, Lin, Guo-Hao, Luan, Kevin W., Mair, Yasmin, Mallya, Sanjay M., Mancinelli-Lyle, Deborah, Marchesan, Julie Teresa, Mariotti, Angelo, Martín, Conchita, Martinez, April G., McDevitt, Michael J., McGregor, Adriana, Mealey, Brian L., Melnick, Philip R., Merin, Robert L., Mehrazarin, Shebli, Miller, Greg W., Miller, Joseph M., Miller, Syrene A., Mincer, Reeva, Mitchell, Julie, Myneni, Srinivas, Nagarajan, Radhakrishnan, Needleman, Ian, Newman, Michael G., Novak, Karen F., Otomo-Corgel, Joan, Pattison, Anna M., Pattison, Gordon L., Pirih, Flavia Q., Polson, Alan M., Preshaw, Philip M., Quirynen, Marc, Rajapuri, Anushri Singh, Reis, Natacha, Robben, Jits, Rossa, Carlos, Jr, Ryan, Maria Emanuel, Sarmiento, Hector L., Scheyer, E. Todd, Schleyer, Titus, Schoenbaum, Todd R., Shanelec, Dennis A., Shin, Kitetsu, Silva, Daniela Rodrigues P., Sourvanos, Dennis, Spear, Frank M., Stacchi, Claudio, Stein, Corey, Takei, Henry H., Tan, Kai Soo, Tarnow, Dennis P., Tetradis, Sotirios, Teughels, Wim, Thumbigere-Math, Vivek, Thyvalikakath, Thankam P., Tibbetts, Leonard S., Trabert, Kenneth C., Turer, Onur Ucak, Urban, Istvan A., Tapia Vazquez, Jose Luis, Vercellotti, Giuseppe, Vercellotti, Tomaso, Wada, Keisuke, Whang, Michael, White, Joel M., Williamson, Megumi A., Wisitrasameewong, Wichaya, Yarascavitch, Carilynne, and Zacher, Adrian Karl

Published
2023
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