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3. Sex-specific differences in the mechanisms for enhanced thromboxane A2-mediated vasoconstriction in adult offspring exposed to prenatal hypoxia.

Author

Graton, Murilo E., Spaans, Floor, He, Rose, Chatterjee, Paulami, Kirschenman, Raven, Quon, Anita, Phillips, Tom J., Case, C. Patrick, and Davidge, Sandra T.

Subjects
ADULT children, VASOCONSTRICTION, PREGNANCY, HYPOXEMIA, MESENTERIC artery, LABORATORY rats, PREGNANCY complications
Abstract

Background: Prenatal hypoxia, a common pregnancy complication, leads to impaired cardiovascular outcomes in the adult offspring. It results in impaired vasodilation in coronary and mesenteric arteries of the adult offspring, due to reduced nitric oxide (NO). Thromboxane A2 (TxA2) is a potent vasoconstrictor increased in cardiovascular diseases, but its role in the impact of prenatal hypoxia is unknown. To prevent the risk of cardiovascular disease by prenatal hypoxia, we have tested a maternal treatment using a nanoparticle-encapsulated mitochondrial antioxidant (nMitoQ). We hypothesized that prenatal hypoxia enhances vascular TxA2 responses in the adult offspring, due to decreased NO modulation, and that this might be prevented by maternal nMitoQ treatment. Methods: Pregnant Sprague–Dawley rats received a single intravenous injection (100 µL) of vehicle (saline) or nMitoQ (125 µmol/L) on gestational day (GD)15 and were exposed to normoxia (21% O2) or hypoxia (11% O2) from GD15 to GD21 (term = 22 days). Coronary and mesenteric arteries were isolated from the 4-month-old female and male offspring, and vasoconstriction responses to U46619 (TxA2 analog) were evaluated using wire myography. In mesenteric arteries, L-NAME (pan-NO synthase (NOS) inhibitor) was used to assess NO modulation. Mesenteric artery endothelial (e)NOS, and TxA2 receptor expression, superoxide, and 3-nitrotyrosine levels were assessed by immunofluorescence. Results: Prenatal hypoxia resulted in increased U46619 responsiveness in coronary and mesenteric arteries of the female offspring, and to a lesser extent in the male offspring, which was prevented by nMitoQ. In females, there was a reduced impact of L-NAME in mesenteric arteries of the prenatal hypoxia saline-treated females, and reduced 3-nitrotyrosine levels. In males, L-NAME increased U46619 responses in mesenteric artery to a similar extent, but TxA2 receptor expression was increased by prenatal hypoxia. There were no changes in eNOS or superoxide levels. Conclusions: Prenatal hypoxia increased TxA2 vasoconstrictor capacity in the adult offspring in a sex-specific manner, via reduced NO modulation in females and increased TP expression in males. Maternal placental antioxidant treatment prevented the impact of prenatal hypoxia. These findings increase our understanding of how complicated pregnancies can lead to a sex difference in the programming of cardiovascular disease in the adult offspring. Highlights: Prenatal hypoxia increases thromboxane-mediated vasoconstrictor responses in both coronary and mesenteric arteries from the adult female and male offspring. This was more pronounced in females, and was prevented by maternal placental antioxidant treatment in pregnancy. The mechanisms for the increased thromboxane-mediated vasoconstrictor responses by prenatal hypoxia exposure were sex-specific, where females had reduced nitric oxide modulation of vasoconstriction, while males had increased thromboxane receptor expression. There are sex-specific differences on how prenatal hypoxia impairs vascular function in the adult offspring. Placenta-targeted therapies in pregnancy should be considered to improve cardiovascular outcomes in the offspring later life but should take the sex of the fetus into consideration. Plain language summary: Prenatal hypoxia, when the fetus does not receive enough oxygen, is a common problem during pregnancy that impacts the developing fetus. It is associated with an increased risk of cardiovascular disease in the offspring in adulthood. While the mechanisms are not fully understood, the blood vessel function in the offspring may be impacted by prenatal hypoxia. We hypothesize that prenatal hypoxia increases the constriction of the blood vessels in the offspring. The placenta, an essential organ for fetal development, supplies oxygen and nutrients to the fetus. In prenatal hypoxia pregnancies, the placenta does not work properly. We have been studying a placental treatment (called nMitoQ) to improve placenta function and thereby the blood vessel function of the offspring. We used a rat model of prenatal hypoxia, where pregnant rats (dams) were placed in a low oxygen environment (hypoxia) during the last trimester of pregnancy. Control rats were kept in normal oxygen conditions. The dams were treated with nMitoQ, or with saline (control). Next, we studied the blood vessels of the offspring in adulthood. We found that prenatal hypoxia increases the constriction of the blood vessels, which was prevented by treating the dams with nMitoQ. Interestingly, this impact was more severe in females compared to males, and the mechanisms were different between the sexes. This study helps in the understanding of how complicated pregnancies can impair cardiovascular health in the offspring, and in a potential development of targeted and sex-specific therapies for those offspring at high risk for future cardiovascular disease. [ABSTRACT FROM AUTHOR]

Published
2024
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6. Sex-Specific Effects of Prenatal Hypoxia and a Placental Antioxidant Treatment on Cardiac Mitochondrial Function in the Young Adult Offspring

Author

Chatterjee, Paulami, primary, Holody, Claudia D., additional, Kirschenman, Raven, additional, Graton, Murilo E., additional, Spaans, Floor, additional, Phillips, Tom J., additional, Case, C. Patrick, additional, Bourque, Stephane L., additional, Lemieux, Hélène, additional, and Davidge, Sandra T., additional

Published
2023
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10. Demonstration of Deployment Accuracy of the Starshade Inner Disk Subsystem

Author

Turse, Dana, Hepper, David, Adams, Larry, Pulford, Mike, Medina, Kamron, Butler, Kassi, Hazelton, Craig, Thomas, Tayler, Tomchek, Andrew, Freebury, Gregg, Stienmier, J. David, Beidleman, Neal, Neff, Kenzo, Kelso, Eric, Bradford, S. Case, Willems, Phil, Lisman, P. Doug, Steeves, John, Webb, David, and Bradford, Samuel Case C

Abstract

We present experimental results that demonstrate the required in-plane deployment accuracy of the starshade Inner Disk Subsystem (IDS). This effort was to address Milestone 7C of the Starshade Technology Activity S5, which requires that the in-plane deployment accuracy of the petal interfaces on the IDS be within +/-300um. A full-scale 10m-diameter IDS prototype was constructed. This prototype comprised a medium-fidelity perimeter truss, medium-fidelity spokes, and a low-fidelity optical shield (OS). The testbed also included gravity compensation systems and a laser tracker metrology system. The post-processed measurement uncertainties of the laser tracker were less than 30um at the 3 sigma level. Design, engineering and fabrication of these components was done by JPL, Tendeg, and Roccor. Testing was performed at the Tendeg facility in Louisville, Colorado. The IDS prototype was deployed 22 times and the locations of petal interfaces on the IDS were measured after each deployment. Based on this data, tolerance intervals were calculated that would contain 99.73% of future deployment accuracy errors with 90% confidence. These tolerance intervals are conservative estimates for 3 sigma bounds. The tolerance intervals for the three pertinent error components were found to be within the required allocations, with at least 19% margin.

Published
2020

11. Demonstration of Deployment Accuracy of the Starshade Inner Disk Subsystem

Author

Bradford, Samuel Case C, Webb, David, Steeves, John, Lisman, P. Doug, Willems, Phil, Bradford, S. Case, Kelso, Eric, Neff, Kenzo, Beidleman, Neal, Stienmier, J. David, Freebury, Gregg, Tomchek, Andrew, Thomas, Tayler, Hazelton, Craig, Butler, Kassi, Medina, Kamron, Pulford, Mike, Adams, Larry, Hepper, David, and Turse, Dana

Published
2020

13. Secretions from placenta, after hypoxia/reoxygenation, can damage developing neurones of brain under experimental conditions

Author

Curtis, Daniel J., Sood, Aman, Phillips, Tom J., Leinster, Veronica H.L., Nishiguchi, Akihiro, Coyle, Christopher, Lacharme-Lora, Lizeth, Beaumont, Oliver, Kemp, Helena, Goodall, Roberta, Cornes, Leila, Giugliano, Michele, Barone, Rocco A., Matsusaki, Michiya, Akashi, Mitsuru, Tanaka, Hiroyoshi Y., Kano, Mitsunobu, McGarvey, Jennifer, Halemani, Nagaraj D., Simon, Katja, Keehan, Robert, Ind, William, Masters, Tracey, Grant, Simon, Athwal, Sharan, Collett, Gavin, Tannetta, Dionne, Sargent, Ian L., Scull-Brown, Emma, Liu, Xun, Aquilina, Kristian, Cohen, Nicki, Lane, Jon D., Thoresen, Marianne, Hanley, Jon, Randall, Andrew, and Case, C. Patrick

Published
2014
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16. The Application of PERT to Large-Scale Educational Research and Evaluation Studies.

Author

Educational Testing Service, Princeton, NJ. and Case, C. Marston

Abstract

The application of a PERT system to a large-scale project will increase the probability of accomplishing project objectives by providing greater visibility of (1) the project objectives, (2) the relationships among the parts of the projects, and (3) the relationships of those component parts to the project objectives. Consequently, educational researchers should find that a PERT system will increase their collective ability to coordinate planning and evaluation efforts. A review of a PERT system applied to a study of disadvantaged school children indicates that in order to achieve optimal utility, the system should be implemented well ahead of the project starting time, and must be responsive to program developments through continued updating procedures. (JH)

Published
1969

17. A Bibliographic Guide to Operations Analysis of Education.

Author

National Center for Educational Statistics (DHEW/OE), Washington, DC. Div. of Data Analysis and Dissemination., Case, C. Marston, and Clark, Stephen C.

Abstract

This bibliography lists 155 books, articles, monographs, and other studies on operations analysis in education. The criteria for inclusion are that the study be quantitative and analytical and use techniques of operations research, systems analysis, management science, program planning and budgeting, benefit analysis, cost analysis, benefit-cost analysis, cost effectiveness analysis, multivariate statistical methods, economics, or computer science. A list of six bibliographies which include most of the studies cited and a list of 38 Technical Notes of the Division of Operations Analysis that are available through ERIC are appended. This document replaces ED 014 129. (HW)

Published
1967

18. ON THE THEORY AND PROCEDURE FOR CONSTRUCTING A MINIMAL-LENGTH, AREA-CONSERVING FREQUENCY POLYGON FROM GROUPED DATA.

Author

National Center for Educational Statistics (DHEW/OE), Washington, DC. and CASE, C. MARSTON

Abstract

THIS PAPER IS CONCERNED WITH GRAPHIC PRESENTATION AND ANALYSIS OF GROUPED OBSERVATIONS. IT PRESENTS A METHOD AND SUPPORTING THEORY FOR THE CONSTRUCTION OF AN AREA-CONSERVING, MINIMAL LENGTH FREQUENCY POLYGON CORRESPONDING TO A GIVEN HISTOGRAM. TRADITIONALLY, THE CONCEPT OF A FREQUENCY POLYGON CORRESPONDING TO A GIVEN HISTOGRAM HAS REFERRED TO THAT POLYGON FORMED BY CONNECTING THE MIDPOINTS OF THE TOPS OF THE RECTANGLES MAKING UP THE HISTOGRAM. THE MOST IMPORTANT DEFICIENCY IN THE TRADITIONAL FREQUENCY POLYGON IS THAT THE AREA OF ANY SPECIFIC RECTANGLE IN THE UNDERLYING HISTOGRAM IS GENERALLY NOT EQUAL TO THE AREA UNDER THE FREQUENCY POLYGON OVER THE SAME INTERVAL. DUE TO THIS DEFICIENCY, DATA ARE SELDOM PRESENTED IN THE FORM OF A FREQUENCY POLYGON. (HW)

Published
1966

19. ON DEPARTURES FROM INDEPENDENCE IN CROSS-CLASSIFICATIONS.

Author

National Center for Educational Statistics (DHEW/OE), Washington, DC. and CASE, C. MARSTON

Abstract

THIS NOTE IS CONCERNED WITH IDEAS AND PROBLEMS INVOLVED IN CROSS-CLASSIFICATION OF OBSERVATIONS ON A GIVEN POPULATION, ESPECIALLY TWO-DIMENSIONAL CROSS-CLASSIFICATIONS. MAIN OBJECTIVES OF THE NOTE INCLUDE--(1) ESTABLISHMENT OF A CONCEPTUAL FRAMEWORK FOR CHARACTERIZATION AND COMPARISON OF CROSS-CLASSIFICATIONS, (2) DISCUSSION OF EXISTING METHODS FOR CHARACTERIZING CROSS-CLASSIFICATIONS, (3) PROPOSAL OF A NEW APPROACH TO AND A NEW METHOD FOR CHARACTERIZING AND MAKING INFERENCES FROM CROSS-CLASSIFICATIONS, AND (4) INDICATION OF HOW MARKOV PROCESSES CAN BE TREATED AS CROSS-CLASSIFICATIONS. THREE KINDS OF PROBABILITIES (UNCONDITIONAL, CONDITIONAL, AND JOINT) ARE DISCUSSED IN TERMS OF STATISTICAL INDEPENDENCE. MEASURES OF ASSOCIATION, ESPECIALLY THE Z-MEASURE OF ASSOCIATION AND ITS RELATION TO THE PHI COEFFICIENT IN VARIOUS SITUATIONS, ARE DISCUSSED AS MEANS OF INVESTIGATING NON-INDEPENDENCE. AN EXAMPLE OF THE Z-MEASURE APPLICATION IS PRESENTED. THE PROCESS OF DERIVING JOINT PROBABILITIES FROM Z-MEASURES AND THE INTERPRETATION OF MARKOV PROCESSES AS CROSS-CLASSIFICATIONS ARE ILLUSTRATED. (HW)

Published
1966

26. Nanoparticle‐encapsulated antioxidant improves placental mitochondrial function in a sexually dimorphic manner in a rat model of prenatal hypoxia

Author

Ganguly, Esha, primary, Kirschenman, Raven, additional, Spaans, Floor, additional, Holody, Claudia D., additional, Phillips, Thomas E. J., additional, Case, C. Patrick, additional, Cooke, Christy‐Lynn M., additional, Murphy, Michael P., additional, Lemieux, Hélène, additional, and Davidge, Sandra T., additional

Published
2021
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32. METAL ON METAL HIP REPLACEMENT

Author

Nolan, J F, Darrah, C, Donell, S T, Wimhurst, J, Toms, A, Marshall, T, Barker, T, Case, C P, Peters, C, and Tucker, J K

Published
2008

33. Molecular Approaches to the Study of Pain

Author

Medhurst, Andrew, primary, Lawson, Sally, additional, Raval, Pravin, additional, Sanger, Gareth, additional, Newton, Richard, additional, Parsons, Andrew, additional, Davey, Philip, additional, Bingham, Sharon, additional, Patrick Case, C, additional, and Piercy, Val, additional

Published
2003
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38. Irish cardiac society: Proceedings of annual general meeting held 20th & 21st November 1992 in Dublin Castle

Author

Cullen, C., MacKenzie, G., Adgey, J., Lavin, F., Keane, M., Forde, A., Shah, P., Gannon, F., Daly, K., McClements, B. M., McNeil, A. J., Wilson, C. M., Webb, S. W., Campbell, N. P. S., Khan, M. M., O’Murchu, B., Gersh, B. J., Bailey, K. R., Holmes, D. R., Foley, D. P., Hermans, W. R., Rensing, B. J., Vos, J., Herman, J-P, Serruys, P. W., Mannion, A., Finn, J., Grimes, H., Lonergan, M., O’Donnell, Daly, L., McGovern, E., Graham, I., Joseph, P. A., Robinson, K., Kinsella, T., Crean, P., Gearty, G., Walsh, M., Ryan, M., Clarke, R., Refsum, R., Ueland, P., Coehrane, D. J., Stewart, A. J., McEneaney, D. J., Allen, J. D., Anderson, J., Dempsey, G., Adgey, A. A. J., Casey, F. A., Mulholland, H. C., Craig, B. G., Power, R., Rooney, N., O’Keeffe, D. B., McComb, J., Wilson, C., Tan, K. S., Pye, C., McCabe, N., Hickey, N., McEneaney, D., Cochrane, D., Oslizlok, P. C., Case, C. L., Gillette, P. C., Knick, Barbara J., Henry, L. P. N., Blair, L., Gumbrielle, T., Bourke, J. P., Hilton, C. J., Campbell, R. W. F., Kearney, P. P., Fennell, F., McKiernan, S., Fennell, W., Escaned, J., Hermans, W. R, Umans, V. A., de Jaegere, P. P., de Feyter, P. J., Galvin, J., Leavey, S., Sugrue, D., Vallely, S. R., Campbell, N. P. S., Laird, J. D., Ferguson, R., Duff, S., Bridges, A. B., Pringle, T. H., McNeill, G. P., McLaren, M., Belch, J. J. F., O’Sullivan, L., Bain, H., Hunter, S., Wren, C., Hennesy, A., Codd, M., Daly, C., McCarthy, C., Carroll, K., Coakley, F., O’Mahony, S., Sullivan, P. A., Kearney, P., Higgins, T., Crowey, J. J, Donnelly, S. M., Tobin, M., FitzGerald, O., Bresnihan, B., Maurer, B. J., Quigley, P. J., Shelley, E., Collins, C., Hickey, N., ulcahy, R., Johnston, P. W., Gibson, J., Crowe, P., King, G., Freyne, P. J., Geary, G., McAdam, B., Sheahan, R., Gaylani, N. El, Simpson, A., Temperley, I., Mulcahy, F., McGee, H. M., Graham, T., Crowe, B., Horgan, J. H., McGinley, J., Hurley, J., Neligan, M., Austin, C., Cleland, J., Gladstone, D., O’Kane, H., O’Sullivan, J., Hasan, A., Hamilton, J. R. L., Hunter, S., Dark, J. H., McDaid, C. M., Phillips, A. S., Lewis, S. A., McMurray, T. J., Walsh, K. P., Abrams, S. E., Diamond, M., Clarkson, M. J., Rutsch, W., Emanuelsson, H., Danchin, N., Wijns, W., and Chappuis, F.

Published
1993
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43. Irish Cardiac Society Proceedings of meeting held 23rd–24th November, 1990

Author

Stanton, A., Kilfeather, S., O’Brien, E., O’Malley, K., Donnelly, M. D. I., Batchelor, Y., McAleer, B., Dalton, G., Turkington, E., Williams, J. R., Varma, M. P. S., Okeefe, S., Redehan, C., Keane, P., Daly, K., Rollins, N. C., Mulholland, H. C., Craig, B., McCann, H. A., Walsh, T. P., Kittrick, H. C., Keelan, E., Codd, M., McCarthy, J., McCarthy, C., Sugrue, D. D., O’Donnell, A. F., Lonergan, M., Daly, L., McGovem, E. M., Keelan, E., Sugrue, D. D., Murphy, J. G., Schwartz, R. S., Garratt, K., Holmes, D. R., Foley, B., Sheehan, R., Kinsella, A., Gearty, G., Walsh, M., Crean, P., Glazier, J. J., Piessens, J., Stammen, F., Vergauwen, V., De Geest, H., Willems, J. L., Quigley, P. J., Ohman, M., Smith, J. E., Stack, R. S., Glazier, J. J., Rickards, A. F., McFadden, E., Clarke, J., Davies, G., Maseri, A., Dickey, W., Adgey, A. A. J., Chew, E. W., Morton, P., Murtagh, J. G., Scott, M. E., O’Keeffe, D. B., O’Murchu, B., Miller, M., Burnett, J. C., Rose, M., Gibney, M., Gearty, G., Crean, P., O’Connor, P., Walsh, M., O’Keeffe, S., Grimes, H., Finn, J., McMurrough, P., Daly, K., Roberts, M. J. D., Pruvis, J. A., McNeill, A. J., Trouton, T. J., Dalzell, T. G. W. N., Dalzell, G. W. N., Flannery, D. J., Wilson, C. M., Patterson, G. C., Webb, S. W., Campbell, N. P. S., Khan, M. M., Molajo, A. O., Adgey, A. A. J., McClements, B. M., Trouton, T. G., Dalzell, G. W. N., Campbell, N. P. S., Webb, S. W., Khan, M. M., Patterson, G. C., Wilson, C. M., Adgey, A. A. J., Flannery, D. J., O’Neill, A. J., Adgey, J., Campbell, N. P. S., Walsh, K., Sreeram, N., Franks, R., Arnold, R., Lonergan, M., Daly, L., Graham, I., Hurley, J., Neligan, M. C., Wood, A. E., de Buitleir, M., Sousa, J., Calkins, H., Rosenheck, S., Langberg, J., Morady, F., Maghur, H. A., Wood, A. E., Neligan, M. C., Murphy, J. G., Gersh, B. J., Oslizok, P., Allen, M., Gillette, R. N., Oslizlok, P., Allen, M., Case, C., Gillette, P. C., Duff, D., Mulholland, C., Craig, B., Mulholland, C., and Duff, D.

Published
1991
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