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Roberto Romero

Publications and source records attributed to Roberto Romero.

136 records · Page 8Linked to original sources
PubMed2002

The CARD15 2936insC mutation and TLR4 896 A>G polymorphism in African Americans and risk of preterm premature rupture of membranes (PPROM).

Infection is believed to be a leading cause of preterm premature rupture of membranes (PPROM). The bacterial cell wall component, lipopolysaccharide (LPS), is thought to initiate tissue responses leading to PPROM in the setting of Gram negative infection. LPS is recognized by the innate immune system, including the proteins encoded by the CARD15 and TLR4 genes. A recently described mutation (2936insC) in CARD15 and a polymorphism in TLR4 896 A>G impair responses to LPS. The objective of this study was to determine if African Americans, who have a higher incidence of PPROM than Caucasians, have different frequencies of the mutant CARD15 allele and the TLR4 hyporesponsive variant, and if risk of PPROM is influenced by fetal carriage of these alleles. The allele frequencies for the CARD15 mutation and the TLR4 896G variant in African Americans were similar to those reported for Caucasians. There was no association between the TLR4 alleles examined and PPROM. However, the CARD15 mutation was only detected in controls and not in PPROM cases. We conclude that the CARD15 mutation and hyporesponsive TLR4 allele do not contribute to ethnic variation in the incidence of PPROM.

Adult↗
PubMed2002

A polymorphism in the matrix metalloproteinase-9 promoter is associated with increased risk of preterm premature rupture of membranes in African Americans.

Fetal membrane rupture is associated with increased expression of matrix metalloproteinase-9 (MMP-9) and matrix degradation. We have determined the functional significance of a variable number tandem repeat and a single nucleotide polymorphism (SNP) in the MMP-9 gene on promoter activity and their association with preterm premature rupture of membranes (PPROM). The 14 CA-repeat allele was a stronger promoter than the 20 CA-repeat allele in amnion epithelial cells and WISH amnion-derived cells, but in THP-1 monocyte/macrophage cells the 14 and 20 CA-repeat alleles had similar activities. An SNP at -1562 did not significantly affect promoter activity. A case-control study of African American neonates revealed that the 14 CA-repeat allele was more common in newborns delivered of mothers who had PPROM than in those delivered at term. There was no association between the -1562 SNP and PPROM. We conclude that there are cell host-dependent differences in MMP-9 promoter activity related to CA-repeat number and that fetal carriage of the 14 CA-repeat allele is associated with PPROM in African Americans.

Black or African American↗
PubMed2002

Pregnancy alters glucose-6-phosphate dehydrogenase trafficking, cell metabolism, and oxidant release of maternal neutrophils.

Pregnancy is associated with changes in host susceptibility to infections and inflammatory disease. We hypothesize that metabolic enzyme trafficking affects maternal neutrophil activation. Specifically, immunofluorescence microscopy has shown that glucose-6-phosphate dehydrogenase (G-6-PDase), the rate-controlling step of the hexose monophosphate shunt (HMS), is located near the cell periphery in control neutrophils but is found near the microtubule-organizing centers in cells from pregnant women. Cytochemical studies confirmed that the distribution of the G-6-PDase antigen is coincident with functional G-6-PDase activity. Metabolic oscillations within activated pregnancy neutrophils are higher in amplitude, though lower in frequency, than activated control neutrophils, suggesting limited HMS activity. Analysis of radioisotope-labeled carbon flux from glucose to CO(2) indicates that the HMS is intact in leukocytes from pregnant women, but its level is not enhanced by cell stimulation. Using extracellular fluorescent markers, activated pregnancy neutrophils were found to release reactive oxygen metabolites (ROMs) at a lower rate than activated control neutrophils. However, basal levels of ROM production in polarized pregnancy neutrophils were greater than in control neutrophils. Microtubule-disrupting agents reversed the observed changes in G-6-PDase trafficking, metabolic oscillations, and ROM production by maternal neutrophils. G-6-PDase trafficking appears to be one mechanism regulating ROM production by maternal neutrophils.

Animals↗
PubMed2002

Amniotic fluid matrix metalloproteinase-8 and the development of cerebral palsy.

AIMS: To examine if increased concentrations of matrix metalloproteinase-8 (MMP-8) in amniotic fluid are associated with the development of cerebral palsy at the age of three years. METHODS: The relationship between amniotic fluid concentrations of MMP-8 and the development of cerebral palsy was examined in 116 preterm singleton newborns (gestational age at birth < 35 weeks) born to mothers who underwent amniocentesis and were followed for at least 3 years. Amniotic fluid was cultured for aerobic and anaerobic bacteria and mycoplasmas. MMP-8 concentrations were measured by specific immunoassays. Cerebral palsy was diagnosed by neuro developmental assessment at the age of three years. RESULTS: Median amniotic fluid concentration of MMP-8 was significantly higher in mothers whose newborns developed cerebral palsy than in mothers whose newborns did not develop cerebral palsy (median 153.9 [range < 0.3-1535.9] ng/ml vs median 6.4 [range < 0.3-3836.8] ng/ml; p < 0.01). Neonates who developed cerebral palsy were delivered at earlier gestational age than those without cerebral palsy. After adjustment for the gestational age at birth and the results of amniotic fluid culture, elevated concentrations of amniotic fluid MMP-8 significantly increased the odds of development of cerebral palsy (odds ratio, 6.0; 95% confidence interval, 1.1-33.0; p < 0.05). CONCLUSION: Increased concentrations of amniotic fluid MMP-8 are associated with the subsequent development of cerebral palsy at the age of 3 years.

Adult↗
PubMed2002

Genetic sonography: a cost-effective method for evaluating women 35 years and older who decline genetic amniocentesis.

OBJECTIVE: To determine whether offering genetic sonography to patients who decline invasive testing can increase the detection rate of trisomy 21 and is cost-effective. METHODS: The detection rate of trisomy 21, the number of pregnancy losses after amniocentesis, and the cost of detecting a single fetus with trisomy 21 were determined in women 35 years and older managed according to the following 3 policies: (1) universal amniocentesis, (2) genetic counseling for maternal age-associated risks for trisomy 21 followed by amniocentesis in patients who elected it, and (3) genetic counseling followed by genetic sonography in patients who originally declined genetic amniocentesis. RESULT: From a population of 40,143 women 35 years and older, the expected number of trisomy 21 fetuses was 349. After genetic counseling, 32% of patients declined invasive testing, resulting in detection of 70% of fetuses with trisomy 21. For universal amniocentesis, the cost to detect 1 fetus with trisomy 21 was $138,036. For the 32% who declined invasive testing after genetic counseling and underwent genetic sonography, the cost to detect a single fetus with trisomy 21 was a function of sensitivity and the screen-positive rate. For screen-positive rates between 5% and 25%, genetic sonography resulted in a cost savings between 14.3% and 18.8% when compared with universal invasive testing and resulted in a considerable increase in detection of fetuses with trisomy 21 (77% to 97%). CONCLUSIONS: A policy of offering genetic sonography followed by amniocentesis to patients 35 years and older who originally decline invasive testing for the diagnosis of trisomy 21 is cost-effective and results in a higher overall detection rate for trisomy 21 without an increased risk of pregnancy loss.

Adult↗
PubMed2002

A diagnostic approach for the evaluation of spina bifida by three-dimensional ultrasonography.

OBJECTIVE: To describe a prenatal diagnostic method for evaluating spina bifida by three-dimensional ultrasonography. METHODS: Two- and three-dimensional ultrasonography were used to determine the extent of vertebral defects among fetuses with spina bifida. Spinal levels were independently counted from the most caudal thoracic vertebra with a rib (e.g., 12th thoracic rib). A virtual cutting plane was manipulated through a volume-rendered spine to generate optimal multiplanar views for this blinded analysis. Prenatal diagnosis was compared with a postnatal analysis of bony spine defects derived from radiographic films or magnetic resonance imaging. RESULTS: Nine fetuses were examined by two-dimensional ultrasonography (21.8 +/- 3.4 menstrual weeks) and three-dimensional ultrasonography (22.8 +/- 4.4 menstrual weeks). For two-dimensional ultrasonography, the spinal level agreed to within 1 vertebral segment in 6 of 9 infants. In contrast, three-dimensional ultrasonography agreed to within 1 vertebral segment in 8 of 9 infants. Three fetuses had vertebral defect levels on two-dimensional ultrasonography that were 1.5 to 2 segments away from postnatal findings. The same fetuses had results that were within 1 vertebral segment on three-dimensional ultrasonography. Volume rendering showed splayed vertebral pedicles and disrupted vertebrae. An intact meningeal sac was easily rendered in 5 of 9 subjects. CONCLUSIONS: Multiplanar views are generally more informative than rendered views for localizing bony defects of the fetal spine. The level of the defect on three-dimensional ultrasonography correlates well with those on two-dimensional ultrasonography and postnatal imaging studies. This approach may improve characterization of spina bifida by adding diagnostic information that is complementary to the initial assessment by two-dimensional ultrasonography.

Female↗
PubMed2002

Three-dimensional ultrasonographic presentation of micrognathia.

OBJECTIVE: To present the variable appearance of micrognathia in fetuses by three-dimensional ultrasonography and to describe practical methods for analysis of these volume data. METHODS: Three-dimensional multiplanar imaging and surface-rendering techniques were used to show various syndromes and diagnostic approaches for the evaluation of fetal micrognathia. RESULTS: Nine cases of fetal micrognathia are presented. Orthogonal multiplanar views were used to obtain a midsagittal facial profile. Examples of micrognathia include 3 cases of Pierre Robin sequence, cerebrocostomandibular syndrome, Cornelia de Lange syndrome, and hypochondrogenesis. Diagnostic pitfalls for micrognathia are also shown. CONCLUSIONS: Three-dimensional multiplanar imaging increases the likelihood that a true midline sagittal view of the facial profile is being analyzed. Surface rendering provides another way to qualitatively evaluate the fetal chin from different viewing perspectives. Three-dimensional ultrasonographic methods are useful adjuncts to the preliminary diagnostic impression from two-dimensional ultrasonography.

Abnormalities, Multiple↗
PubMed2001

A single nucleotide polymorphism in the matrix metalloproteinase-1 (MMP-1) promoter influences amnion cell MMP-1 expression and risk for preterm premature rupture of the fetal membranes.

Interstitial collagen gives fetal membranes tensile strength, and membrane rupture has been attributed to collagen degradation. A polymorphism at -1607 in the matrix metalloproteinase-1 (MMP-1) promoter (an insertion of a guanine (G)) creates a core Ets binding site and increases promoter activity. We investigated whether this polymorphism is functionally significant for MMP-1 expression in amnion cells and whether it is associated with preterm premature rupture of the membranes (PPROM). The 2G promoter had >2-fold greater activity than the 1G allele in amnion mesenchymal cells and WISH amnion cells. Phorbol 12-myristate 13-acetate (PMA) increased mesenchymal cell nuclear protein binding with greater affinity to the 2G allele. Induction of MMP-1 mRNA by PMA was significantly greater in cells with a 1G/2G or 2G/2G genotype compared with cells homozygous for the 1G allele. When treated with PMA, the 1G/2G and 2G/2G cells produced greater amounts of MMP-1 protein than 1G/1G cells. A significant association was found between fetal carriage of a 2G allele and PPROM. We conclude that the 2G allele has stronger promoter activity in amnion cells, that it confers increased responsiveness of amnion cells to stimuli that induce MMP-1, and that this polymorphism contributes to the risk of PPROM.

Amnion↗
PubMedDate not supplied

Interferon gamma antagonizes interleukin-1beta-induced cyclooxygenase-2 expression and prostaglandin E(2) production in human myometrial cells.

OBJECTIVE: To evaluate the effect of interferon gamma (IFNgamma) on interleukin-1beta (IL-1) and tumor necrosis factor-alpha (TNFalpha)-promoted prostaglandin E(2) (PGE(2)) production and to investigate the interaction of IFNgamma and IL-1 on cyclooxygenase-2 (COX-2) expression, as well as nuclear factor-kappaB (NF-kappaB) activation in human myometrial cells. METHODS: An immortalized human myometrial cell line was cultured in Dulbecco modified Eagle medium (DMEM) fortified with 10% (v/v) fetal calf serum (FCS) in multiwell plates until near confluency. Twenty-four hours before the start of the experiments, the medium was replaced with FCS-free medium containing 0.5% bovine serum albumin. Prostaglandin E(2) was determined in the medium with a specific radioimmunoassay having a sensitivity of 10 pg. The COX-2 and NF-kappaB inhibitory protein (IkappaB) protein levels were measured in cell extracts by Western blot. RESULTS: Cell cultures primed with IFNgamma produced significantly less (P <.05-.01) PGE(2) in response to cytokines than cells exposed to IL-1, TNF-alpha, or the combination of the two. This result corresponded to a similar inhibition of IkappaB degradation (a prerequisite of NF-kappaB activation) as well as COX-2 protein steady state levels. CONCLUSION: Interferon gamma acts as a partial antagonist of IL-1 signaling in this cell model at a site upstream from the activation of the NF-kappaB pathway, causing a partial inhibition of COX-2 expression and PGE(2) production.

Blotting, Western↗