- Pelvic floor disorders treatments
- Endometriosis Research and Treatment
- Anorectal Disease Treatments and Outcomes
- Pregnancy-related medical research
- Reproductive System and Pregnancy
- Preterm Birth and Chorioamnionitis
- Hernia repair and management
- Ion channel regulation and function
- Ovarian function and disorders
- Pelvic and Acetabular Injuries
- Nitric Oxide and Endothelin Effects
- Estrogen and related hormone effects
- Pregnancy and preeclampsia studies
- Neuroendocrine regulation and behavior
- Uterine Myomas and Treatments
- Protein Kinase Regulation and GTPase Signaling
- Connective tissue disorders research
- Urinary Bladder and Prostate Research
- Cardiovascular Issues in Pregnancy
- Renin-Angiotensin System Studies
- Cardiomyopathy and Myosin Studies
- Growth Hormone and Insulin-like Growth Factors
- Reproductive Biology and Fertility
- Neonatal Respiratory Health Research
- Receptor Mechanisms and Signaling
The University of Texas Southwestern Medical Center
2013-2022
Institute for Female Pelvic Medicine and Reconstructive Surgery
2008-2017
Southwestern Medical Center
2004-2014
American Urogynecologic Society
2011
Astellas Pharma (Japan)
2011
McGill University
2009
University of Arizona
1984-2009
Weatherford College
2009
Florida College
2009
University of Florida
2009
Amniotic membrane has been applied to the ocular surface restore corneal function. The beneficial effect of amniotic transplantation may be due immunosuppressive effects epithelial cells. purpose this study was determine whether cells (AECs) secrete anti-inflammatory and antiproliferative factors that affect chemotaxis neutrophils macrophages suppress both T- B-cell proliferation in vitro.Human were isolated from human cultured vitro. supernatants AEC cultures collected after 48 hours...
Successful delivery of the fetus (parturition) depends on coordinate interactions between uterus and cervix. A majority (70%) mice deficient in type 1 isozyme steroid 5α-reductase fail to deliver their young at term thus manifest a parturition defect. Using vitro vivo measurements we show here that rhythmic contractions occur normally these mutant end gestation. In contrast, cervix animal fails ripen as judged by biomechanical, histological, endocrinological assays. Impaired metabolism...
Cervical remodeling during pregnancy and parturition is a single progressive process that can be loosely divided into four overlapping phases termed softening, ripening, dilation/labor, post partum repair. Elucidating the molecular mechanisms facilitate all of cervical critical for an understanding identifying processes are misregulated in preterm labor, significant cause perinatal morbidity. In present study, biomechanical measurements indicate softening was initiated between gestation days...
Excessive secretion of aldosterone from the adrenal results in most common form endocrine hypertension. An understanding regulatory processes involved synthesis and release is needed to define biomolecular mechanisms controlling excessive production aldosterone. However, vitro studies regarding human have been limited because difficulties obtaining tissue subsequent isolation aldosterone-secreting glomerulosa cells. Herein we describe an adrenocortical carcinoma cell line, NCI-H295, which...
Aberrant up-regulation of aromatase in eutopic endometrium and implants from women with endometriosis has been reported. Aromatase induction may be mediated by increased cyclooxygenase-2 (COX-2). Recently, we demonstrated that progesterone receptor (PR)-A PR-B serve an antiinflammatory role the uterus antagonizing nuclear factor κB activation COX-2 expression. PR-C, which antagonizes PR-B, is up-regulated inflammation. Although estrogen α (ERα) implicated endometriosis, ERβ suggested. We...
Rationale : Loss of fibulin-4 during embryogenesis results in perinatal lethality because aneurysm rupture, and defective elastic fiber assembly has been proposed as an underlying cause for the phenotype. However, aneurysms are never seen mice deficient elastin, or fibulin-5, which absence also leads to compromised fibers. Objective We sought determine mechanism development establish role aortic development. Methods Results generated germline smooth muscle cell (SMC)-specific deletion gene (...
Pelvic organ prolapse (POP) is a common condition affecting almost half of women over the age 50. The molecular and cellular mechanisms underlying this condition, however, remain poorly understood. Here we have reported that fibulin-5, an integrin-binding matricellular protein essential for elastic fiber assembly, regulated activity MMP-9 to maintain integrity vaginal wall prevented development POP. In murine stromal cells, fibulin-5 inhibited β1 integrin–dependent, fibronectin-mediated...
Several strategies have been described for the primary culture of human myometrial cells.However, cultures cells a limited life span, making continual tissue acquisition and cell isolation necessary.Recent studies demonstrated that span is related to chromosomal telomere length, cellular senescence results from progressive shortening lack telomerase expression.Transfection with expression vectors containing reverse transcriptase (hTERT) maintains length effectively gives normal an unlimited...
Identification of temporal and spatial changes in myometrial gene expression during parturition may further the understanding coordinated regulation contractions parturition. The objective this study was to compare profiles human fundal myometrium from pregnant women before after onset labor using a functional genomics approach, characterize patterns three genes believed be important Fundal mRNA isolated five not labor, analyzed UniGEM-V microarrays with 9182 cDNA elements. Real-time...
The conversion of C19 steroids to estrogens occurs in a number tissues and is catalyzed by specific form cytochrome P450, namely aromatase P450 (P450arom). Previously, radiolabeled androstenedione estrone has been demonstrated uterine leiomyomas. By use reverse transcription followed polymerase chain reaction amplification total RNA together with rat cRNA as an internal standard, we detected quantified P450arom transcripts isolated from 32 the 35 leiomyoma (91%) 18 24 adjacent myometrial...
Stimulation of tracheal smooth muscle cells in culture with ionomycin resulted a rapid increase cytosolic free Ca2+ concentration ([Ca2+]i) and an both myosin light chain kinase phosphorylation. These responses were markedly inhibited the absence extracellular Ca2+. Pretreatment 1-[N-O-bis(5-isoquinolinesulfonyl)-N- methyl-L-tyrosyl]-4-phenylpiperazine (KN-62), specific inhibitor multifunctional calmodulin-dependent protein II (CaM II), did not affect [Ca2+]i but ionomycin-induced...
Studies have shown that labor occurs primarily in the night/morning hours. Recently, we identified human myometrium as a target for melatonin (MEL), neuroendocrine output signal coding circadian night.The purpose of this study was to determine effects MEL on contractility and contractile machinery telomerase-immortalized myometrial cells.To ascertain effect vitro, performed gel retraction assays with cells exposed iodomelatonin +/- oxytocin (OT). The gap junctions were also investigated....
Increased synthesis of cervical hyaluronan (HA) from early to late pregnancy has long been proposed play an essential role in disorganization the collagen-rich extracellular matrix allow for maximal compliance and dilation cervix during birth process. Here, we show that HA is not increased distensibility pregnancy. Rather, cervicovaginal plays unanticipated important epithelial barrier protection lower reproductive tract. Specifically, depletion vagina resulted inappropriate differentiation...
Pelvic organ prolapse (POP) increases in prevalence with age; recurrence after surgical repair is common.The objective of the study was to determine effects local estrogen treatment on connective tissue synthesis and breakdown vaginal wall postmenopausal women planning POP.This a randomized trial.The conducted at an academic tertiary medical center.Postmenopausal uterus symptomatic anterior and/or apical stage 2 or greater participated study.Estrogen (Premarin) placebo cream for 6 weeks...
Smooth muscle contraction is initiated primarily by an increase in intracellular Ca2+, Ca(2+)-dependent activation of myosin light chain kinase, and phosphorylation chain. In this investigation, we identified pregnancy-associated alterations phosphorylation, force contraction, content contractile proteins human myometrium. Steady-state levels stress were correlated positively both tissues, but the myometrial strips from pregnant women developed more at any given level phosphorylation. During...
Experimental and clinical studies in a variety of nonprimate species demonstrate that progesterone withdrawal leads to changes gene expression initiate parturition at term. Mice deficient 5alpha-reductase type I fail undergo cervical ripening term despite the timely onset luteolysis blood.Our objective was test hypothesis estrogen metabolism is regulated tissues during pregnancy, even which not characterized by blood.Estradiol quantified intact from nonpregnant pregnant women before or after...
Adenosine 3',5'-cyclic monophosphate (cAMP) is believed to be an important mediator of myometrial relaxation, and there evidence suggest that guanosine (cGMP) a smooth muscle relaxation in vascular probably nonvascular tissues. To investigate the biochemical mechanisms involved regulation human contractility, we studied effects analogues cAMP cGMP, as well activators adenylate guanylate cyclases, on uterine contractile activity. We found cells culture respond cGMP cAMP, cyclase, with...
The objective of this study was to compare the effects systemic and local estrogen treatment on collagen assembly biomechanical properties vaginal wall. Ovariectomized nulliparous rats were treated with estradiol or conjugated equine estrogens (CEEs) either systemically, CEE, placebo cream for 4 wk. Low-dose CEE resulted in increased epithelial thickness significant growth without uterine hyperplasia. Furthermore, wall distensibility compromise maximal force at failure. Systemic modest...