The applicant is dedicated to the pursuit of a career in academic medicine; to that end, she seeks to acquire additional research skills that will enable her to conduct independent research. She is an Obstetrician-Gynecologist who will complete subspecialty training in Maternal-Fetal Medicine June 30, 1988. She also holds the Master of Arts degree in Cell Biology. The applicant is highly motivated to address one of the major health problems of our time, viz, preterm birth. To do so, an innovative research strategy has been developed. The hypothesis to be tested in the research proposed in this application is that infection-induced preterm labor is caused by bioactive agents of infection that serve to effect increased prostaglandin formation in decidua. Based on this proposition, the long-range goals of the research proposed are (i) define the biomolecular events operative in the initiation of preterm labor in pregnancies complicated by infection and (ii) to ascertain whether selected biomolecular processes involved in infection-associated preterm labor are uniquely appropriate as a model for the study of spontaneous parturition. To accomplish the long-range goals of this research and to provide optimal opportunity for the applicant to acquire the investigative skills necessary for independent research, we propose five specific aims as follow: The goals of aim 1 are (i) to establish, characterize, and validate assays for the quantification of bacterial endotoxin (lipopolysaccharide (LPS)), tumor necrosis factor/cachectin (TNF-alpha), interleukin-1 (IL-1), and colony stimulating factor(s) (CSF(s)) in amniotic fluid and (ii) to ascertain if bioactive agents of infection (LPS or selected cytokines or both), which may accumulate in amniotic fluid, are more sensitive indices and more informative guides to the pathophysiology of infection-complicated preterm labor than are examinations directed toward identifying infection by bacteriologic criteria. The goal of aim 2 is to define the mechanism(s) by which bioactive agents of infection cause preterm labor. Specifically, are selected cytokines, produced in response to infection, instrumental in the stimulation of prostaglandin formation in decidua? The goal of aim 3 is to make use of the data obtained in the research conducted to address aims 1 and 2 to establish a system for the classification of the causes of preterm labor. The goal of aim 4 is to investigate the regulation of cytokine production by the macrophage-like uterine decidua vera tissue and cytotrophoblasts of placenta; and we will evaluate the mechanisms that are operative in the expression of receptors for cytokines in decidua, chorion leave, amnion, and villous trophoblastic tissues. The goal of aim 5 is to provide the opportunity for the applicant to perform the research proposed in an academic-research environment that is conducive to the acquisition of research skills necessary for the conduct of independent investigation. This research will be conducted in the Cecil H. and Ida Green Center for Reproductive Biology Sciences. Basis and clinical scientists work side-by-side in this center to address biomedical problems of common interest.
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| Cox, S M; King, M R; Casey, M L et al. (1993) Interleukin-1 beta, -1 alpha, and -6 and prostaglandins in vaginal/cervical fluids of pregnant women before and during labor. J Clin Endocrinol Metab 77:805-15 |
| Cox, S M; Shelburne, P; Mason, R et al. (1991) Mechanisms of hemolysis and anemia associated with acute antepartum pyelonephritis. Am J Obstet Gynecol 164:587-90 |
| Waldron, K W; Renou, P M; Lolatgis, N et al. (1990) Second-trimester termination with 16,16 dimethyl-PGE1-methyl ester (gemeprost), compared with a regimen that included intra-amniotic PGF2 alpha and hypertonic saline. Reprod Fertil Dev 2:495-8 |
