Biomedical subjects

James M Roberts

Publications and source records attributed to James M Roberts.

At least 37 records · Page 2Linked to original sources

PubMed2006

Intracellular adhesion molecule concentrations in women who smoke during pregnancy.

OBJECTIVE: Smoking and endothelial dysfunction are associated with adverse pregnancy outcomes. The effect of smoking on vascular endothelium during pregnancy has not been well studied. Our objectives were to determine if smoking has an impact on endothelial function in pregnancy by comparing markers of endothelial function and to evaluate the contribution from different cellular sources. METHODS: We measured markers of endothelial function in a prospective cohort of 198 primiparous women who had 325 plasma samples obtained throughout pregnancy. Samples were assayed for intracellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin. Smoking status was determined by serum cotinine concentration. Analyses of adhesion molecules were performed for 4 gestational age intervals by using Mann-Whitney and Kruskal-Wallis tests. Gene expression for ICAM-1 was determined by real-time polymerase chain reaction from placental biopsies. A human umbilical vein endothelial cell (HUVEC) culture model was utilized to evaluate the effect of cotinine on endothelial cell production of ICAM-1. RESULTS: ICAM-1 is increased, VCAM-1 was not different, and E-selectin was decreased among smokers at various times during pregnancy. Placental production of ICAM-1 was decreased in women who smoked (P = .02) as measured by real-time polymerase chain reaction. Human umbilical vein endothelial cells production of ICAM-1 increased with heavy concentrations of cotinine exposure (P < .01). CONCLUSION: Smoking during pregnancy is associated with vascular perturbations, as evidenced by increased concentrations of serum ICAM-1. It appears unlikely that the source of the increased ICAM-1 is the placenta. The endothelium most likely contributes to increased maternal ICAM-1 in heavy smokers, but a leukocyte source cannot be ruled out. LEVEL OF EVIDENCE: II-2.

Adult↗

PubMed2006

Maternal androgen and estrogen concentrations are not associated with blood pressure changes in uncomplicated pregnancies.

Systolic blood pressure increase between the second and third trimester of pregnancy has been associated with a substantially reduced maternal breast cancer risk, and it has been suggested that elevated androgens mediate the association. Androgen and estrogen concentrations were measured in maternal serum collected in 86 uncomplicated, singleton pregnancies. Overall, there were no consistent or statistically significant patterns of association between the hormones and systolic, diastolic, or mean arterial blood pressure or blood pressure change between trimesters. Results were similar with adjustment for factors related to the hormones. These data are not consistent with the hypothesis that elevated androgen concentrations mediate the observed reduction in maternal breast cancer risk associated with increases in blood pressure over the pregnancy.

Adult↗

PubMed2006

Variability in cerebral oxygen delivery is reduced in premature neonates exposed to chorioamnionitis.

Premature infants exposed to chorioamnionitis are at increased risk for periventricular leukomalacia (PVL) and intraventricular hemorrhage (IVH), lesions that may result from inflammation and/or fluctuations in cerebral blood flow. The effect of chorioamnionitis on near-infrared spectroscopy (NIRS) measures of cerebral oxygen delivery has not been evaluated previously. Forty-nine infants born at 25-31 6/7 wk gestation underwent NIRS examination on d 1, 2, 3, and 7 of life. Variability in NIRS tracings was analyzed by partitioning each tracing into three components: long-term, intermediate, and short-term variability; the latter two components were analyzed. Chorioamnionitis-exposed infants manifest reduced intermediate variability in cerebral oxygenated and deoxygenated Hb but not total Hb. Infants with severe IVH/PVL had the lowest intermediate variability on d 1. Short-term variability was similar between chorioamnionitis-exposed and unexposed infants, and between infants with versus without severe IVH or PVL. We conclude that intermediate-term variability in NIRS cerebral oxygen delivery is reduced in chorioamnionitis-exposed infants. We speculate that intermediate variability represents the important time frame for evaluating the pathogenesis of perinatal brain injury. Further studies are needed to determine how these findings relate to cerebral blood flow autoregulation and oxygen utilization in premature infants.

Brain↗

PubMed2005

Accuracy and reliability of maternal recall of infant birth weight among older women.

PURPOSE: We assessed the accuracy and reliability of maternal recall of infant birth weight 35 to 70 years after delivery. METHODS: A total of 120 well functioning women (mean age 80 years; 45% Black) reported the birth weight for each live birth and then provided documentation of birth weights (n = 22) or reported birth weights a second time (n = 98). RESULTS: Agreement between recalled and documented birth weights was high for first births (ICC = 0.96) but moderate for subsequent births (ICC = 0.59). Maternal recall was highly reliable for first births (r = 0.95) and subsequent births (r = 0.87), and reliability remained high when considered separately by race, education, income, and age. CONCLUSION: Women report accurate and reliable infant birth-weight data an average of 57 years after delivery, and recall is particularly precise for first births.

Age Factors↗

PubMed2005

Inflammation and triglycerides partially mediate the effect of prepregnancy body mass index on the risk of preeclampsia.

The objective of this study was to quantify the mediating role of inflammation and triglycerides in the association between prepregnancy body mass index (weight (kg)/height (m)2) and preeclampsia. The authors conducted a nested case-control study of 55 preeclamptic women and 165 pregnant controls from the Pregnancy Exposures and Preeclampsia Prevention Study (Pittsburgh, Pennsylvania, 1997-2001). Serum samples collected at < or = 20 weeks' gestation were analyzed for levels of C-reactive protein and triglycerides. The adjusted odds ratio (AOR) from a multivariable conditional logistic regression model assessing the total effect of body mass index on preeclampsia risk was compared with the AOR from the same model after results were controlled for C-reactive protein, triglycerides, and confounding factors (direct-effects model). The percentage of the total effect that was mediated through inflammation and triglycerides was calculated as 100 - [ln(direct-effects AOR)/ln(total-effects AOR)]. In the total-effects model, 4- and 8-unit increases in body mass index were associated with 1.7-fold (95% confidence interval (CI): 1.3, 2.3) and 2.9-fold (95% CI: 1.6, 5.2) increases in preeclampsia risk, whereas in the direct-effects model, these AORs were 1.4 (95% CI: 1.0, 1.9) and 2.0 (95% CI: 1.0, 3.8), respectively. Inflammation was a more important mediator than triglycerides. These findings suggest that approximately one third of the total effect of body mass index on preeclampsia risk is mediated through inflammation and triglyceride levels.

Adult↗

PubMed2005

Uric acid is as important as proteinuria in identifying fetal risk in women with gestational hypertension.

Gestational hypertension is differentiated into higher and lower risk by the presence or absence of proteinuria. We asked if hyperuricemia, a common finding in pregnancy hypertension, might also be an indicator of increased risk. We examined fetal outcome data from 972 pregnancies collected from 1997 to 2002 in a nested case-control study. Participants were nulliparous with no known medical complications. The frequency of preterm birth, the duration of pregnancy, frequency of small-for-gestational-age infants, and birth weight centile were determined for pregnancies assigned to 8 categories by the presence or absence of combinations of hypertension, hyperuricemia, and proteinuria. In women with gestational hypertension, hyperuricemia was associated with shorter gestations and smaller birth weight centiles and increased risk of preterm birth and small-for-gestational-age infants. Hyperuricemia increased the risk of these outcomes in the presence or absence of proteinuria. Risk was also increased in a small group of women with hyperuricemia and proteinuria without hypertension. Women with only hypertension and hyperuricemia have similar or greater risk as women with only hypertension and proteinuria. Those with hypertension, proteinuria, and hyperuricemia have greater risk than those with hypertension and proteinuria alone. The risk of these outcomes increased with increasing uric acid. Hyperuricemia is at least as effective as proteinuria at identifying gestational hypertensive pregnancies at increased risk. Uric acid should be reexamined for clinical and research utility.

Adult↗

PubMed2005

Preeclampsia: recent insights.

Preeclampsia is a pregnancy complication with serious consequences for mother and infant. The disorder is diagnosed by gestational hypertension and proteinuria but is far more than pregnancy induced hypertension. Preeclampsia is proposed to occur in 2 stages. Stage 1 reduced placental perfusion is postulated as the root cause and to lead to the maternal syndrome, Stage 2. Why perfusion is reduced, how this translates to a maternal disease in some but not all women and what is the linkage of the 2 stages are topics of intense study. In the last decade such studies have provided valuable insights into pathophysiology that now guide ongoing clinical trials.

Endocrinology↗

PubMed2005

Effect of smoking on uric acid and other metabolic markers throughout normal pregnancy.

OBJECTIVES: Smoking, pregnancy, and preeclampsia are all associated with changes in markers of the metabolic syndrome. Several markers are increased in all three conditions. However, smoking is negatively associated with preeclampsia, and therefore some markers would be expected to behave differently in smokers during pregnancy. We compared several metabolic markers of the metabolic syndrome in healthy primigravid smokers and nonsmokers over normal pregnancy to explore mechanisms for the reduced risk of preeclampsia in smokers. STUDY DESIGN: Plasma was obtained from 63 women throughout pregnancy who delivered at term. Smoking status was determined by urinary cotinine concentrations measured by HPLC. Uric acid, creatinine, free fatty acids, triglycerides, and total cholesterol were measured with diagnostic kits. Data were analyzed by repeated-measures ANOVA. RESULTS: The smoking groups were not different by delivery gestational age, maternal age, body mass index, or race. Uric acid, cholesterol, and triglyceride concentrations increased during pregnancy (significant for time, P < 0.0001). Mean uric acid and creatinine concentrations were different by smoking status (P < 0.001 and P = 0.046). Nonsmokers had the lowest concentrations of uric acid, and women who quit smoking had the highest concentrations. Uric acid concentrations remained significantly different controlling for serum creatinine CONCLUSIONS: Women have changes in markers of the metabolic syndrome during pregnancy, and uric acid is further influenced by smoking. The difference in uric acid concentrations by smoking status may be secondary to increased production through the xanthine oxidase pathway but is not simply a result of altered glomerular function because the association persists after controlling for creatinine.

Adult↗

PubMed2005

Soluble fms-like tyrosine kinase 1 is increased in preeclampsia but not in normotensive pregnancies with small-for-gestational-age neonates: relationship to circulating placental growth factor.

CONTEXT: An excess of the soluble receptor, fms-like tyrosine kinase 1 (sFlt-1) may contribute to maternal vascular dysfunction in women with preeclampsia by binding and thereby reducing concentrations of free vascular endothelial growth factor and placental growth factor (PlGF) in the circulation. The putative stimulus for increased sFlt-1 during preeclampsia, placental hypoxia due to poor perfusion, is common to both preeclampsia and idiopathic intrauterine growth restriction. However, the latter condition occurs without maternal vascular disease. OBJECTIVE: We asked whether, as with preeclampsia, sFlt-1 is increased and free PlGF is decreased in villous placenta and maternal serum of normotensive women with small-for-gestational-age (SGA) neonates. STUDY DESIGN: This was a case-control study using banked samples. Groups of women with SGA neonates (birth weight centile < 10th) and women with preeclampsia were matched to separate sets of normal pregnancy controls based on gestational age at blood sampling (serum) or gestational age at delivery (placenta). RESULTS: sFlt-1 levels were higher in preeclamptics than controls (serum, P < 0.0001; placental protein, P = 0.03; placental mRNA, P = 0.007) but not increased in SGA pregnancies. PlGF was lower in both preeclampsia (serum, P < 0.0001; placental protein, P = 0.05) and SGA (serum, P = 0.0008; placental protein, P = 0.03) compared with their controls. PlGF in preeclampsia and SGA groups did not differ. CONCLUSIONS: These data are consistent with a role for sFlt-1 in the maternal manifestations of preeclampsia. In contrast to preeclampsia, sFlt-1 does not appear to contribute substantially to decreased circulating free PlGF in SGA pregnancies in the absence of a maternal syndrome.

Adult↗

PubMed2005

The risk of preeclampsia rises with increasing prepregnancy body mass index.

PURPOSE: To explore the dose-dependent relation between prepregnancy body mass index (BMI) and the risk of preeclampsia after adjusting for measured confounders. METHODS: We studied 1179 primiparous women who enrolled at < 16 weeks' gestation into a prospective cohort study of the pathogenesis of preeclampsia. Multivariable logistic regression was used to quantify the independent effect of prepregnancy BMI on the risk of preeclampsia after adjusting for race and smoking status. BMI was specified as a restricted quadratic spline. RESULTS: Preeclampsia risk rose strikingly from a BMI of 15 to 30 kg/m(2). Compared with women with a BMI of 21, the adjusted risk of preeclampsia doubled at a BMI of 26 (odds ratio 2.1 [95% confidence interval, 1.4, 3.4]), and nearly tripled at a BMI of 30 (2.9 [1.6, 5.3]). Women with a BMI of 17 had a 57% reduction in preeclampsia risk compared with women with a BMI of 21 (0.43 [0.25, 0.76]), and a BMI of 19 was associated with a 33% reduction in risk (0.66 [0.50, 0.87]). CONCLUSIONS: These results indicate that preeclampsia risk rises through most of the BMI distribution. The dramatic elevation in overweight prevalence in the United States may increase preeclampsia incidence in the future.

Adolescent↗

PubMed2005

A mouse model for cyclin E-dependent genetic instability and tumorigenesis.

Ubiquitination of murine cyclin E is triggered by phosphorylation on threonine 393. Cyclin E(T393A) knockin mice exhibited increased cyclin E stability, but no phenotypic abnormalities. Importantly, loss of the p53 pathway exacerbated the effect of the T393A mutation. Thus, in p21(-/-) cells the T393A mutation had an exaggerated effect on cyclin E abundance and its associated kinase activity, which caused abnormal cell cycle progression, and genetic instability involving chromosome breaks and translocations. Moreover, cyclin E(T393A) acted synergistically with p53 deficiency to accelerate tumorigenesis in cyclin E(T393A) p53(-/-) mice; Ras more readily transformed cyclin E(T393A) p53(-/-) cells than p53(-/-) cells in vitro; and cyclin E(T393A) mice had a greatly increased susceptibility to Ras-induced lung cancer.

Animals↗

PubMed2005

The uriscreen test to detect significant asymptomatic bacteriuria during pregnancy.

BACKGROUND: Asymptomatic bacteriuria (ASB) occurs in 2-11% of pregnancies and it is a clear predisposition to the development of acute pyelonephritis, which, in turn, poses risk to mother and fetus. Treatment of bacteriuria during pregnancy reduces the incidence of pyelonephritis. Therefore, it is recommended to screen for ASB at the first prenatal visit. The gold standard for detection of bacteriuria during pregnancy is urine culture, but this test is expensive, time-consuming, and labor-intensive. OBJECTIVE: To determine the reliability of an enzymatic urine screening test (Uriscreen; Savyon Diagnostics, Ashdod, Israel) for detecting ASB in pregnancy. METHODS: Catheterized urine samples were collected from 150 women who had routine prenatal screening for ASB. Patients with urinary symptoms, active vaginal bleeding, or who were previously on antibiotics therapy were excluded from the study. Sensitivity, specificity, and the positive and negative predictive values for the Uriscreen were estimated using urine culture as the criterion standard. Urine cultures were considered positive if they grew >10(5) colony-forming units of a single uropathogen. RESULTS: Twenty-eight women (18.7%) had urine culture results indicating significant bacteriuria, and 17 of these 28 specimens had positive enzyme activity. Of 122 samples with no growth, 109 had negative enzyme activity. Sensitivity, specificity, and positive and negative predictive values for the Uriscreen test were 60.7% (+/-18.1), 89.3% (+/-5.6), 56.6%, and 90.8%, respectively. CONCLUSION: The Uriscreen test had inadequate sensitivity for rapid screening of bacteriuria in pregnancy.

Adult↗

PubMed2005

Second pregnancy outcomes following preeclampsia in a first pregnancy.

OBJECTIVES: We compared second pregnancy outcomes among women with and without preeclampsia in their first pregnancies who all had second pregnancies without preeclampsia. METHODS: One hundred thirty women with and 6148 without preeclampsia in their first pregnancies, who all had nonpreeclamptic second pregnancies, were included. Outcomes, including delivery gestational age, birthweight, small-for-gestational-age (SGA), and preterm delivery were compared. RESULTS: Overall, second pregnancy outcomes were not different between women with and without preeclampsia in their first pregnancy. However, when women were stratified by gestational timing of preeclampsia, women with preeclampsia at < 34 weeks (N = 22) had smaller infants and delivered earlier in their second nonpreeclamptic pregnancy compared to women with later preeclampsia (N = 108) or no preeclampsia in the first pregnancy. Women with early preeclampsia also had an increased risk of prematurity (< 37 weeks) in second pregnancies that persisted after controlling for confounding factors [Odds ratio (OR = 3.2)]. DISCUSSION: Second, nonpreeclamptic pregnancy outcomes are different between women with previous early preeclampsia and controls but not between late preeclampsia and controls. These findings support other epidemiological data indicating differences between early and late onset preeclampsia as well as a potential relationship of preeclampsia and spontaneous preterm birth.

Adult↗

PubMed2005

Maternal plasma homocysteine concentrations are not increased in twin pregnancies.

OBJECTIVE(S): We tested the hypothesis that twin pregnancies would lead to increased maternal plasma homocysteine. We further hypothesized that twin pregnancies complicated by preeclampsia would have increased plasma homocysteine compared to twin pregnancies without preeclampsia and normal singleton pregnancies. METHODS: Plasma was collected at delivery from 127 nulliparous subjects: 57 women with normal singleton pregnancies, 39 women with singleton and preeclampsia, 17 women with uncomplicated twin pregnancies, and 14 women with twins and preeclampsia. Subjects were group matched for prepregnancy body mass index (BMI) and race. Plasma homocysteine was analyzed by high pressure liquid chromatography (HPLC) with fluorescence detection, and plasma folic acid was measured by radio immunoassay (RIA). RESULTS: The mean plasma concentration of homocysteine was significantly increased in all women with preeclampsia (7.4+/-2.9 microM) compared to all normal pregnant women (5.9+/-2.1 microM, p=0.002). However, homocysteine was not significantly increased in all women with twins (6.7+/-2.1 microM) compared to all women with singleton pregnancies (6.5+/-2.7 microM, p=0.61). In addition, women with twins and preeclampsia did not have increased homocysteine (6.8+/-2.1 microM) compared to women with twins and normal pregnancy (6.7+/-2.1 microM, p=0.72). As expected, because of extra supplementation, plasma folic acid was significantly increased in women with twins (27.9+/-11.6 ng/mL) compared to women with singleton pregnancies (20.8+/-8.5 ng/mL, p=0.0003). However, folic acid was not different between preeclamptics and controls (23.5+/-10.8 vs. 21.9+/-9.2 ng/mL respectively, p=0.36). Lastly, there was a significant inverse correlation between homocysteine and folic acid among all the subjects (r2=- 0.053, p< 0.01), and this correlation persisted in the women with singleton pregnancies (r2=- 0.078, p< 0.01), but was lost in the twins (r2=- 0.073, p=0.14). CONCLUSIONS: With contemporary management including increased folic acid supplementation, plasma homocysteine is not increased in twin pregnancies with or without preeclampsia.

Adult↗

PubMed2005

Placental system A transporter mRNA is not different in preeclampsia, normal pregnancy, or pregnancies with small-for-gestational-age infants.

OBJECTIVE: System A amino acid transporter activity is reduced in placentas from small-for-gestational-age (SGA) compared to normal pregnancies. We compared the expression of the system A transporters between preeclamptic and control and between small-for-gestational-age and controls pregnancies. METHODS: We used placental samples from 18 preeclamptic pregnancies matched with 17 normal pregnancies and from 16 SGA pregnancies matched with 15 different normal pregnancies. Using real-time reverse transcriptase-polymerase chain reaction (RT-PCR) we quantified the mRNA for two system A subtype target genes ATA1 and ATA2 as well as beta-actin for normalization. RESULTS: There was no significant difference of mRNA for ATA1 or ATA2 transporters between preeclamptic and their controls or SGA pregnancies and their controls. CONCLUSIONS: Despite previous studies reporting reduced activity for system A transporters in small-for-gestational-age pregnancies, we found no difference in steady-state concentrations of the mRNA, of the system A transporters among preeclamptic, SGA, and normal control pregnancies. These results do not exclude differences in actual protein levels or activity of the amino acid transporters, which warrant further study.

Adult↗

PubMed2005

Early occurrence of metabolic syndrome after hypertension in pregnancy.

OBJECTIVE: The objective of the present study was to evaluate the cardiovascular risk profile and the prevalence of metabolic syndrome among women with a history of pregnancy-induced hypertension (PIH). METHODS: From a cohort of 3,799 nulliparous women prospectively recruited between 1989 and 1997, we performed an observational study on 168 case-control pairs 7.8 years after delivery. Participants were scheduled for a visit with a research nurse to evaluate their cardiovascular risk profile using a questionnaire, anthropometric measurements and blood specimen analysis. RESULTS: One hundred sixty-eight women with prior PIH (105 with gestational hypertension and 63 with preeclampsia) and 168 controls matched for age and year of index delivery were evaluated. The women with PIH (34.6 +/- 4.4 years) were more obese and had higher systolic (115 mm Hg versus 108 mm Hg) and diastolic (75 mm Hg versus 70 mm Hg) blood pressures (P < .001) than the 168 controls (35.1 +/- 4.5 years). They had lower high-density lipoprotein cholesterol level (1.30 mmol/L versus 1.42 mmol/L; P < .001), increased fasting blood glucose concentration (5.2 mmol/L versus 5.0 mmol/L; P = .002), and higher insulin levels (119 versus 91 pmol/L; P < .001). The prevalence of the metabolic syndrome was higher in the PIH group (unadjusted odds ratio = 4.9; 95% confidence interval 2.1-10.9) compared with controls, even after adjustment for confounders (adjusted odds ratio = 3.6; 95% confidence interval 1.4 -9.0). CONCLUSION: In white women in their mid-30s, the prevalence of the metabolic syndrome is 3- to 5-fold increased in those with a history of PIH in their first pregnancy. This emphasizes the importance of long-term follow-up assessment for cardiovascular risk factors in these women.

Adult↗

PubMed2004

N-acetylation and ubiquitin-independent proteasomal degradation of p21(Cip1).

Expression of the CDK inhibitor p21(Cip1) is tightly regulated by signals that control cell division. p21 is an unstable protein that is degraded by the proteasome; however, the pathway that leads to proteasomal degradation of p21 has proven to be enigmatic. An important issue is whether proteasomal degradation of p21 occurs independently of ubiquitylation or, alternatively, whether ubiquitylation on its N terminus is crucial. We resolve this uncertainty by showing that endogenous cellular p21 is completely acetylated at its amino terminus and is therefore not a substrate for N-ubiquitylation. We further show that inactivation of essential components of the ubiquitylation machinery does not directly impact endogenous p21 degradation. Our results underscore the importance of N-acetylation in restricting N-ubiquitylation and show, in particular, that ubiquitylation of endogenous p21 either at internal lysines or on the N terminus is unlikely to control its degradation by the proteasome.

Acetylation↗

PubMed2004

Living with or without cyclins and cyclin-dependent kinases.

Entry into, progression through, and exit from the G1 phase of the mammalian cell cycle in response to extracellular mitogenic cues are presumed to be governed by cyclin-dependent kinases (Cdks) regulated by the D-type and E-type cyclins. Studies performed over more than a decade have supported the view that these holoenzymes are important, if not required, for these processes. However, recent experiments in which the genes encoding all three D-type cyclins, the two E-type cyclins, cyclin D-dependent Cdk4 and Cdk6, or cyclin E-dependent Cdk2 have been disrupted in the mouse germ line have revealed that much of fetal development occurs normally in their absence. Thus, none of these genes is strictly essential for cell cycle progression. To what extent is the prevailing dogma incorrect, and how can the recent findings be reconciled with past work?

Animals↗