PubMed Health⌕ Search

Biomedical subjects

B Mercer

Publications and source records attributed to B Mercer.

At least 19 recordsLinked to original sources
PubMed2004

Term human fetal membranes have a weak zone overlying the lower uterine pole and cervix before onset of labor.

The etiology of fetal membrane (FM) rupture is unknown. A hypothesis that the FM weakens by a process of collagen remodeling and apoptosis to facilitate rupture has been proposed. Human FMs reportedly exhibit a zone of altered histology, postulated to be the FM rupture site, but concomitant FM weakness has not been demonstrated. We hypothesized that a discrete zone of FM with marked weakness, histological change, and evidence of remodeling and apoptosis, develops in late gestation in the FM overlying the cervix. FM tissue from women undergoing prelabor cesarean delivery were perioperatively marked to identify the FM overlying the cervix, cut with a procedure that facilitates remapping the rupture strength of FM pieces to their former location and orientation on a three-dimensional model, and tested for strength. A 10-cm FM zone centered at the cervical mark was compared with the remaining FM. Mean rupture strength within the cervical zone was 55% of the remaining FM. The cervical zone also exhibited increased MMP-9 protein, decreased tissue inhibitor of metalloproteinases-3 (TIMP-3) protein, and increased PARP cleavage coincident with the previously reported zone of altered histology. A discrete zone of weakness is present in term prelabor FMs overlying the cervix and has biochemical characteristics consistent with tissue remodeling and apoptosis.

Apoptosis↗
PubMed2001

The Preterm Prediction Study: association between cervical interleukin 6 concentration and spontaneous preterm birth. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

OBJECTIVE: The aim of this study was to determine the interrelationship between cervical concentration of interleukin 6 and detection of fetal fibronectin and other risk factors for spontaneous preterm birth. STUDY DESIGN: All patients with spontaneous preterm birth at <35 weeks' gestation (case patients; n = 125) and subjects matched for race, parity, and center delivered at > or = 37 weeks' gestation (n = 125; control subjects) were selected from women enrolled in the National Institute of Child Health and Human Development's Preterm Prediction Study. Interleukin 6 concentrations were determined by enzyme-linked immunosorbent assay in cervical swabs obtained at 22 weeks' to 24 weeks 6 days' gestation. Cutoffs to define an elevated interleukin 6 concentration included the 90th and 95th percentiles for control subjects (>305 and >538 pg/mL, respectively). RESULTS: The mean (+/-SD) interleukin 6 concentration was significantly higher in case patients than in control subjects (212 +/- 339 vs 111 +/- 186 pg/mL; P = .008). With either cutoff value elevated interleukin 6 concentration was significantly associated with spontaneous preterm birth (90th percentile, 20% vs 9.6%; P = .02; 95th percentile, 12% vs 4.8%; P = .04). Cervical interleukin 6 levels were highest within 4 weeks of delivery, and the trend continued until term. Elevated interleukin 6 concentration was not significantly associated with bacterial vaginosis, maternal body mass index <19.8 kg/m2, or a short cervix (< or = 25 mm), but it was significantly associated with a positive cervicovaginal fetal fibronectin test result (90th percentile, odds ratio, 5.5; 95% confidence interval, 2.6-11.9; 95th percentile, odds ratio, 5.3, 95% confidence interval, 2.1-12.9). The mean interleukin 6 concentration among women with a positive fibronectin test result was 373 +/- 406 pg/mL; that among women with a negative fetal fibronectin test result was 130 +/- 239 pg/mL (P = .001). In a regression analysis that adjusted for risk factors significantly associated with spontaneous preterm birth in this population (positive fetal fibronectin test result, body mass index <19.8 kg/m2, vaginal bleeding in the first or second trimester, previous spontaneous preterm birth, and short cervix) elevated cervical interleukin 6 concentration was not independently associated with spontaneous preterm birth (odds ratio, 1.8; 95% confidence interval, 0.8-4.3). CONCLUSIONS: At 24 weeks' gestation cervical interleukin 6 concentration in women who subsequently had a spontaneous preterm birth at <35 weeks' gestation was significantly elevated relative to those who were delivered at term. The association was particularly strong within 4 weeks of testing. A positive fetal fibronectin test result was strongly associated with elevated cervical interleukin 6 concentration, but bacterial vaginosis was not.

Case-Control Studies↗
PubMed2000

MEF2 responds to multiple calcium-regulated signals in the control of skeletal muscle fiber type.

Different patterns of motor nerve activity drive distinctive programs of gene transcription in skeletal muscles, thereby establishing a high degree of metabolic and physiological specialization among myofiber subtypes. Recently, we proposed that the influence of motor nerve activity on skeletal muscle fiber type is transduced to the relevant genes by calcineurin, which controls the functional activity of NFAT (nuclear family of activated T cell) proteins. Here we demonstrate that calcineurin-dependent gene regulation in skeletal myocytes is mediated also by MEF2 transcription factors, and is integrated with additional calcium-regulated signaling inputs, specifically calmodulin-dependent protein kinase activity. In skeletal muscles of transgenic mice, both NFAT and MEF2 binding sites are necessary for properly regulated function of a slow fiber-specific enhancer, and either forced expression of activated calcineurin or motor nerve stimulation up-regulates a MEF2-dependent reporter gene. These results provide new insights into the molecular mechanisms by which specialized characteristics of skeletal myofiber subtypes are established and maintained.

Animals↗
PubMed2000

Stimulation of slow skeletal muscle fiber gene expression by calcineurin in vivo.

Adult skeletal muscle fibers can be categorized into fast and slow twitch subtypes based on specialized contractile and metabolic properties and on distinctive patterns of muscle gene expression. Muscle fiber-type characteristics are dependent on the frequency of motor nerve stimulation and are thought to be controlled by calcium-dependent signaling. The calcium, calmodulin-dependent protein phosphatase, calcineurin, stimulates slow fiber-specific gene promoters in cultured skeletal muscle cells, and the calcineurin inhibitor, cyclosporin A, inhibits slow fiber gene expression in vivo, suggesting a key role of calcineurin in activation of the slow muscle fiber phenotype. Calcineurin has also been shown to induce hypertrophy of cardiac muscle and to mediate the hypertrophic effects of insulin-like growth factor-1 on skeletal myocytes in vitro. To determine whether activated calcineurin was sufficient to induce slow fiber gene expression and hypertrophy in adult skeletal muscle in vivo, we created transgenic mice that expressed activated calcineurin under control of the muscle creatine kinase enhancer. These mice exhibited an increase in slow muscle fibers, but no evidence for skeletal muscle hypertrophy. These results demonstrate that calcineurin activation is sufficient to induce the slow fiber gene regulatory program in vivo and suggest that additional signals are required for skeletal muscle hypertrophy.

Animals↗
PubMed2000

Direct activation of a GATA6 cardiac enhancer by Nkx2.5: evidence for a reinforcing regulatory network of Nkx2.5 and GATA transcription factors in the developing heart.

The zinc finger transcription factors GATA4, -5, and -6 and the homeodomain protein Nkx2.5 are expressed in the developing heart and have been shown to activate a variety of cardiac-specific genes. To begin to define the regulatory relationships between these cardiac transcription factors and to understand the mechanisms that control their expression during cardiogenesis, we analyzed the mouse GATA6 gene for regulatory elements sufficient to direct cardiac expression during embryogenesis. Using beta-galactosidase fusion constructs in transgenic mice, a 4.3-kb 5' regulatory region that directed transcription specifically in the cardiac lineage, beginning at the cardiac crescent stage, was identified. Thereafter, transgene expression became compartmentalized to the outflow tract, a portion of the right ventricle, and a limited region of the common atrial chamber of the embryonic heart. Further dissection of this regulatory region identified a 1.8-kb cardiac-specific enhancer that recapitulated the expression pattern of the larger region when fused to a heterologous promoter and a smaller 500-bp subregion that retained cardiac expression, but was quantitatively weaker. The GATA6 cardiac enhancer contained a binding site for Nkx2.5 that was essential for cardiac-specific expression in transgenic mice. These studies demonstrate that GATA6 is a direct target gene for Nkx2.5 in the developing heart and reveal a mutually reinforcing regulatory network of Nkx2.5 and GATA transcription factors during cardiogenesis.

Animals↗
PubMed2000

The preterm prediction study: cervical lactoferrin concentration, other markers of lower genital tract infection, and preterm birth. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

OBJECTIVE: This study was undertaken to determine the relationship among cervical lactoferrin concentration, other cervical markers potentially related to infection, and spontaneous preterm birth. STUDY DESIGN: Cervical lactoferrin concentrations obtained at 22 to 24 weeks' gestation among 121 women who had a spontaneous preterm birth <35 weeks' gestation were compared with cervical lactoferrin concentrations among 121 women matched for race, parity, and center who were delivered at >/=37 weeks' gestation. Results were compared against levels of cervical interleukin 6, fetal fibronectin, and sialidase, against cervical length according to ultrasonography, and according to the bacterial vaginosis Gram stain score. RESULTS: Cervical lactoferrin concentrations ranged from not measurable (19% of the concentrations were below the threshold for this assay) to a titer of >/=1:64. There was no significant difference in the overall distributions of lactoferrin concentrations between the case patients and control subjects (P =.18). Only when the highest titers of lactoferrin were considered were there more women in the spontaneous preterm birth group (6/121 vs 0/121; P =.03). According to Spearman correlation analyses the cervical lactoferrin concentrations were strongly related to interleukin 6 concentration (r =.51; P =.0001), sialidase activity (r =.38; P =.0001), and bacterial vaginosis (r =.38; P =.0001), were weakly related to fetal fibronectin (r =. 16; P =.01), and were not related to cervical length. With the 90th percentile (a dilution of 1:32) used as a cutoff to establish a dichotomous variable, lactoferrin concentration had the following odds ratios and 95% confidence intervals for associations with other potential markers of infection: bacterial vaginosis odds ratio, 4.8 (95% confidence interval, 2.2-10.3); interleukin 6 concentration odds ratio, 2.8 (95% confidence interval, 1.2-6.5); sialidase activity odds ratio, 5. 5 (95% confidence interval, 2.2-13.7); fetal fibronectin concentration odds ratio, 0.6 (95% confidence interval, 0.2-2.0); chlamydiosis odds ratio, 2.3 (95% confidence interval, 0.8-6.9); and short cervix odds ratio, 0.5 (95% confidence interval, 0.2-1.4). CONCLUSIONS: Lactoferrin found in the cervix correlated well with other markers of lower genital tract infection. High lactoferrin levels were associated with spontaneous preterm birth but had a very low predictive sensitivity.

Bacterial Infections↗
PubMed2000

The Preterm Prediction Study: association of second-trimester genitourinary chlamydia infection with subsequent spontaneous preterm birth.

OBJECTIVE: This study was undertaken to determine the association between genitourinary tract infection with Chlamydia trachomatis and spontaneous preterm birth. STUDY DESIGN: Genitourinary tract infection with C trachomatis was determined with a ligase chain reaction assay of voided urine samples collected at 24 weeks' gestation (22 weeks' to 24 weeks 6 days' gestation) and 28 weeks' gestation (27 weeks' to 28 weeks 6 days' gestation). Case patients (spontaneous preterm birth at <37 weeks' gestation; n = 190) and control subjects (delivery at >/=37 weeks' gestation, matched for race, parity, and center; n = 190) were selected from 2929 women enrolled in the Preterm Prediction Study of the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. RESULTS: Genitourinary C trachomatis infection (11% overall) was significantly more common among the case patients than among the control subjects at 24 weeks' gestation (15.8% vs 6.3%; P =.003) but not at 28 weeks' gestation (12.6% vs 10.9%; P =.61). Women with chlamydia infection were more likely to have bacterial vaginosis (57.1% vs 32.9%; P =.002) and a short cervical length (</=25 mm; 33.0% vs 17.9%; P =.02) but not a body mass index <19.8 kg/m(2) (35.0% vs 23.9%; P =.17) or a positive fetal fibronectin test result (7.1% vs 9.5%; P =.62). After adjustment for risk factors for spontaneous preterm birth, women with C trachomatis infection at 24 weeks' gestation were 2 times as likely as uninfected women to have a spontaneous preterm birth at <37 weeks' gestation (odds ratio, 2.2; 95% confidence interval, 1.03-4.78) and 3 times as likely to have a spontaneous preterm birth at <35 weeks' gestation (odds ratio, 3.2; 95% confidence interval, 1.08-9.57). CONCLUSION: Genitourinary C trachomatis infection at 24 weeks' gestation was associated with a 2-fold to 3-fold increased risk of subsequent spontaneous preterm birth.

Adolescent↗
PubMed2000

The preterm prediction study: quantitative fetal fibronectin values and the prediction of spontaneous preterm birth. The National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

OBJECTIVE: A cervicovaginal fetal fibronectin value of >/=50 ng/mL has been used to define women at risk of having a preterm birth. We evaluated the relationship between quantitative fetal fibronectin values and spontaneous preterm birth. STUDY DESIGN: Cervical and vaginal specimens for fetal fibronectin were obtained at 24, 26, 28, and 30 weeks' gestation from 2926 women. Quantitative fetal fibronectin values were calculated by using absorbances determined by enzyme-linked immunosorbent assay. The highest fetal fibronectin value (cervical or vaginal) for each woman at each visit was evaluated in relation to spontaneous preterm birth at <35 weeks' gestation. Receiver operating characteristic curves were constructed to determine the optimal cutoff point for fetal fibronectin values to predict spontaneous preterm birth at <35 weeks' gestation and within 4 weeks of testing. RESULTS: The risk of spontaneous preterm birth increased as a function of increasing fetal fibronectin values from approximately 20 to 300 ng/mL. Fetal fibronectin values > or =300 ng/mL were not associated with a further increase in spontaneous preterm birth. Examination of the receiver operating characteristic curve indicates that the optimal cutoff point for a positive fetal fibronectin test result at 24 to 30 weeks' gestation to predict spontaneous preterm birth at <35 weeks is between 45 and 60 ng/mL. CONCLUSION: Increasing levels of cervicovaginal fetal fibronectin up to 300 ng/mL are associated with an increasing risk of spontaneous preterm birth. Nevertheless, at 24 to 30 weeks, the value currently used, 50 ng of fetal fibronectin per milliliter, appears to be a reasonable cutoff point for predicting spontaneous preterm birth at <35 weeks' gestation.

Cervix Uteri↗
PubMed2000

Risk factors and opportunities for prevention of early-onset neonatal sepsis: a multicenter case-control study.

BACKGROUND: Early-onset group B streptococcal (GBS) prevention efforts are based on targeted use of intrapartum antibiotic prophylaxis (IAP); applicability of these prevention efforts to infections caused by other organisms is not clear. METHODS: Multicenter surveillance during 1995 to 1996 for culture-confirmed, early-onset sepsis in an aggregate of 52 406 births; matched case-control study of risk factors for GBS and other sepsis. RESULTS: Early-onset disease occurred in 188 infants (3.5 cases per 1000 live births). GBS (1.4 cases per 1000 births) and Escherichia coli (0.6 cases per 1000 births) caused most infections. GBS sepsis less often occurred in preterm deliveries compared with other sepsis. Compared with gestation-matched controls without documented sepsis, GBS disease was associated with intrapartum fever (matched OR, 4.1; CI, 1.2-13.4) and frequent vaginal exams (matched OR, 2.9; CI, 1.1-8. 0). An obstetric risk factor-preterm delivery, intrapartum fever, or membrane rupture >/=18 hours-was found in 49% of GBS cases and 79% of other sepsis. IAP had an adjusted efficacy of 68.2% against any early-onset sepsis. Ampicillin resistance was evident in 69% of E coli infections. No deaths occurred among susceptible E coli infections, whereas 41% of ampicillin-resistant E coli infections were fatal. Ninety-one percent of infants who developed ampicillin-resistant E coli infections were preterm, and 59% of these infants were born to mothers who had received IAP. CONCLUSIONS: Either prenatal GBS screening or a risk-based strategy could potentially prevent a substantial portion of GBS cases. Sepsis caused by other organisms is more often a disease of prematurity. IAP seemed efficacious against early-onset sepsis. However, the severity of ampicillin-resistant E coli sepsis and its occurrence after maternal antibiotics suggest caution regarding use of ampicillin instead of penicillin for GBS prophylaxis.

Ampicillin Resistance↗
PubMed1999

The preterm prediction study: failure of midtrimester cervical sialidase level elevation to predict subsequent spontaneous preterm birth.

OBJECTIVE: Our objective was to determine any associations among midtrimester cervical fluid sialidase activity, bacterial vaginosis, and subsequent spontaneous preterm birth. STUDY DESIGN: In this nested case-control study all patients (n = 126) with spontaneous preterm birth at <35 weeks' gestation and selected control subjects delivered at >/=37 weeks' gestation (n = 126, matched for race, parity, and center) were derived from women enrolled in the multicenter National Institute of Child Health and Human Development Preterm Prediction Study. Sialidase activity and presence of bacterial vaginosis according to Gram stain were determined in cervical swabs and vaginal smears, respectively, obtained at 22 weeks' to 24 weeks 6 days' gestation. RESULTS: The mean +/- SD sialidase activities were similar in case patients and control subjects (0.64 +/- 1.60 vs 0.41 +/- 0.94 nmol. mL-1. min-1, P =.21). Neither sialidase activity above the 90th percentile (10.3% vs 9.5%, P =.8) nor sialidase activity above the 95th percentile (7.9% vs 4. 8%, P =.3) of control specimens (>1.43 and >2.23 nmol. mL-1. min-1, respectively) was associated with spontaneous preterm birth. The frequency of combinations of bacterial vaginosis and elevated sialidase activity was similar (P >/=.63 with either cutoff) in case patients and control subjects. Sialidase activity was significantly higher among women with bacterial vaginosis than among those without bacterial vaginosis (1.35 +/- 1.87 vs 0.03 +/- 0.14 nmol. mL-1. min-1, P <.0001). CONCLUSIONS: Elevated cervical fluid sialidase activity at 22 to 24 weeks' gestation did not distinguish women at increased risk for spontaneous preterm birth, nor did it discriminate a subgroup of patients who had bacterial vaginosis associated with spontaneous preterm birth.

Case-Control Studies↗
PubMed1999

Obstetrical determinants of neonatal neurological morbidity in < or = 1000-gram infants.

The purpose of this study is to identify obstetrical factors associated with adverse neurological outcome in < or =1000-g infants. In a 1-year (1992-1993) observational study, the NICHD MFMU Network collected obstetrical risk factors for 486 infants who weighed < or =1000 g at birth and who survived > 2 days. Infants' records were abstracted for seizures, intraventricular hemorrhage, and an abnormal neurological evaluation. Seventy-nine (16%) infants had a Grade III or IV intraventricular hemorrhage, 46 (9%) developed seizures and 57 (14%) had an abnormal neurological evaluation. Both lower birth weight and earlier gestational age correlated (P <0.01) with an increasing incidence of all three outcomes. Several other factors appeared to be associated with neurological morbidity, however, after controlling for potential confounders in the multivariate analyses, most of these factors were no longer significant. African-American race, odds ratio (OR) 0.6 (0.3-1.0), and severe preeclampsia, OR 0.2 (0.1-0.7), were protective against intraventricular hemorrhage. Maternal treatment with corticosteroids did not impact neurological outcome in this study population. We conclude that, in a population of < or =1000-g infants, lower birth weight and earlier gestational age were the only consistently significant predictors of all three adverse neurological outcomes.

Alabama↗
PubMed1999

Control of early cardiac-specific transcription of Nkx2-5 by a GATA-dependent enhancer.

The homeobox gene Nkx2-5 is the earliest known marker of the cardiac lineage in vertebrate embryos. Nkx2-5 expression is first detected in mesodermal cells specified to form heart at embryonic day 7.5 in the mouse and expression is maintained throughout the developing and adult heart. In addition to the heart, Nkx2-5 is transiently expressed in the developing pharynx, thyroid and stomach. To investigate the mechanisms that initiate cardiac transcription during embryogenesis, we analyzed the Nkx2-5 upstream region for regulatory elements sufficient to direct expression of a lacZ transgene in the developing heart of transgenic mice. We describe a cardiac enhancer, located about 9 kilobases upstream of the Nkx2-5 gene, that fully recapitulates the expression pattern of the endogenous gene in cardiogenic precursor cells from the onset of cardiac lineage specification and throughout the linear and looping heart tube. Thereafter, as the atrial and ventricular chambers become demarcated, enhancer activity becomes restricted to the developing right ventricle. Transcription of Nkx2-5 in pharynx, thyroid and stomach is controlled by regulatory elements separable from the cardiac enhancer. This distal cardiac enhancer contains a high-affinity binding site for the cardiac-restricted zinc finger transcription factor GATA4 that is essential for transcriptional activity. These results reveal a novel GATA-dependent mechanism for activation of Nkx2-5 transcription in the developing heart and indicate that regulation of Nkx2-5 is controlled in a modular manner, with multiple regulatory regions responding to distinct transcriptional networks in different compartments of the developing heart.

Animals↗
PubMed1998

The effect of maternal magnesium sulfate treatment on neonatal morbidity in < or = 1000-gram infants.

We evaluated the effect of maternal magnesium sulfate treatment on selected neonatal outcomes in < or =1000-g infants. In a 1-year (1992-1993) observational study, the National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units collected outcome data for 799 infants whose birth weights were < or =1000 g. Only singleton infants, with a gestational age >20 weeks who were not the product of an induced abortion were included. Our analysis was further limited to those infants without major congenital anomalies, who were deemed potentially viable by the obstetrician, whose mother would have undergone a cesarean delivery for fetal indications, and who survived greater than 2 days. Outcomes were compared in infants whose mothers did and did not receive magnesium sulfate for labor tocolysis. Among the 124 women who did and the 184 who did not receive magnesium sulfate tocolytic therapy, the frequencies of grade III or IV intraventricular hemorrhage (16 vs. 20%, p = 0.34), seizure activity (7 vs. 10%, p = 0.35), grade III or IV retinopathy of prematurity (21 vs. 18% p = 0.59), abnormal neurological exam (28 vs. 28%, p = 0.91), intact survival to 120 days or to discharge (48 vs. 44%, p = 0.54), and infant mortality (23 vs. 31%, p = 0.10) were similar. Multiple logistic regression analysis was used to control for the effect of potential confounders (specifically, gestational age) and confirmed the lack of a significant association between maternal magnesium sulfate treatment for tocolysis and selected neonatal outcomes in this population of < or =1000-gram infants.

Adult↗
PubMed1998

Contortrostatin, a homodimeric snake venom disintegrin, is a potent inhibitor of osteoclast attachment.

Disintegrins are small disulfide-rich proteins containing an Arg-Gly-Asp (RGD) sequence near their carboxyl terminus. These polypeptides inhibit binding of adhesion molecules to their receptors (integrins) on the surface of cells. Osteoclasts express integrins, heterodimeric cell surface adhesion receptors, that have been shown to be involved in interactions with the extracellular matrix (ECM), including attachment to bone and bone resorption. It has recently been shown that disintegrins effectively inhibit attachment of osteoclasts to components of the ECM and also disrupt osteoclast-mediated bone resorption. Here we characterize the effects of contortrostatin (CTS), a novel homodimeric snake venom disintegrin, on osteoclast attachment. Plastic dishes coated with CTS were able to support osteoclast attachment with a high affinity (EC50,CTS = 86 +/- 6.7 nM) similar to that of vitronectin (VTN; EC50,VTN = 80 +/- 20 nM). Further, CTS was observed to inhibit completely osteoclast attachment to fetal bovine serum (FBS; IC50,FBS = 0.36 +/- 0.04 nM) and VTN (IC50,VTN = 0.85 +/- 0.13 nM). We used monoclonal antibodies directed against the beta1 (monoclonal antibody [MAb] CD29) and beta3 (MAb F11) integrin subunits to explore the mechanism of osteoclast attachment to immobilized CTS. Only MAb F11 inhibited attachment to immobilized CTS (IC50 = 0.41 +/- 0.12 microg/ml), suggesting that binding to CTS is mediated in part by a beta3 integrin, presumably the alpha(v)beta3 VTN receptor. In further support of an integrin-mediated mechanism, binding of osteoclasts to CTS is inhibited by the RGD peptide, GRGDSP. CTS was also more potent (IC50,FBS = 0.36 +/- 0.04 nM) at inhibiting osteoclast attachment to FBS-coated wells than the monomeric snake venom disintegrin echistatin (IC50,FBS = 8.9 +/- 1.5 nM) or VTN (IC50FBS = 97.5 +/- 25.5 nM). Taken together, these data suggest that the snake venom disintegrin CTS is a potent inhibitor of beta3 integrin-mediated osteoclast attachment, presumably involving the VTN receptor (an alpha[v]beta3 integrin). Further studies of the mechanism of CTS-osteoclast interactions may aid in the design of peptide mimetics to act as antiresorptive agents for the treatment of osteoporosis and other skeletal pathology.

Animals↗
PubMed1997

Evidence for serum response factor-mediated regulatory networks governing SM22alpha transcription in smooth, skeletal, and cardiac muscle cells.

SM22alpha is an adult smooth muscle-specific protein that is expressed in the smooth, cardiac, and skeletal muscle lineages during early embryogenesis before becoming restricted specifically to all vascular and visceral smooth muscle cells (SMC) in late fetal development and adulthood. We have used the SM22alpha gene as a marker to define the regulatory mechanisms that control muscle-specific gene expression in SMCs. Previously, we reported that the 445-base-pair promoter of SM22alpha was sufficient to direct transcription of a lacZ reporter gene in early cardiac and skeletal muscle cell lineages and in a subset of arterial SMCs, but not in venous nor visceral SMCs in transgenic mice. Here we describe two evolutionarily conserved CArG (CC(A/T)6GG) boxes in the SM22alpha promoter, both of which are essential for full promoter activity in cultured SMCs. In contrast, only the promoter-proximal CArG box is essential for specific expression in developing smooth, skeletal, and cardiac muscle lineages in transgenic mice. Both CArG boxes bind serum response factor (SRF), but SRF binding is not sufficient for SM22alpha promoter activity, since overexpression of SRF in the embryonal teratocarcinoma cell line F9, which normally expresses low levels of SRF, fails to activate the promoter. However, a chimeric protein in which SRF was fused to the transcription activation domain of the viral coactivator VP16 is able to activate the SM22alpha promoter in F9 cells. These results demonstrate the SM22alpha promoter-proximal CArG box is a target for the regulatory programs that confer smooth, skeletal, and cardiac muscle specificity to the SM22alpha promoter and they suggest that SRF activates SM22alpha transcription in conjunction with additional regulatory factors that are cell type-restricted.

Animals↗
PubMed1996

Postoperative incision complications after cesarean section in patients with antepartum syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP): does delayed primary closure make a difference?

OBJECTIVE: Our purpose was to evaluate wound complications between patients with antepartum HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome with primary closure versus delayed closure and Pfannenstiel versus midline skin incisions. STUDY DESIGN: Medical records of patients with antepartum HELLP syndrome undergoing cesarean section were examined for type and timing of skin closure: Pfannenstiel versus midline skin incision and primary versus delayed closure. The immediate (before hospital discharge) and late (2-week postoperative check) wound complications were analyzed with respect to timing of wound closure and type of skin incision. RESULTS: A total of 104 patients were identified; 75 had a primary skin closure and 29 had a delayed closure 48 to 72 hours postoperatively. Immediate wound complications (wound infection, hematoma), occurred in 18 (26%) patients who had primary closure versus 8 (24%) who had a delayed closure, odds ratio 1.13 (95% confidence interval 0.39 to 3.27). A late wound breakdown was seen in only 1 patient with primary closure but in none with delayed closure. There were no fascial wound dehiscences. No statistical difference in wound complication was found between midline (primary, delayed) and Pfannenstiel (primary, delayed) incisions, odds ratio 0.65 (95% confidence interval 0.23 to 1.88). CONCLUSION: In women with antepartum HELLP syndrome delivered by cesarean section the frequency of wound complications is not influenced by type of skin incision or time of skin closure (primary or delayed).

Adult↗
PubMed1996

Prenatal diagnosis of genital anomalies.

OBJECTIVES: This is a report of five cases of abnormal fetal genitalia detected by routine prenatal ultrasound. METHODS: Retrospective review was conducted to identify all cases of abnormal fetal genitalia identified by routine obstetrical ultrasound at our institution in which postpartum follow-up was available. RESULTS: Five cases of prenatal sonographically diagnosed abnormal fetal genitalia were confirmed postnatally. The abnormalities include ambiguous genitalia, severe hypospadias with unilateral cryptorchidism, megalourethra, and concealed penis. In all cases, other anomalies were discovered during the prenatal ultrasound. CONCLUSIONS: Prenatal ultrasound may detect a variety of abnormalities of the fetal genitalia.

Female↗