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Biomedical subjects

D M Olson

Publications and source records attributed to D M Olson.

At least 37 records · Page 2Linked to original sources
PubMed2000

Maternal smoking and preeclampsia.

OBJECTIVE: To study the relationship between maternal smoking and preeclampsia and whether this association differs between primiparous and multiparous women. STUDY DESIGN: We conducted a population-based, retrospective, cohort study of 58,216 singleton pregnancies from northern and central Alberta, Canada, between 1995 and 1997. Multivariate logistic regression was used to control for maternal alcohol consumption, drug dependence, maternal age, maternal weight, prior intrauterine growth restriction and other confounders. RESULTS: Maternal smoking was associated with a significantly reduced overall risk of preeclampsia (adjusted odds ratio [aOR]: .61; 95% confidence interval [CI]: .50-.75; P < .01). Stratified analyses showed that in primiparous pregnancies, maternal smoking was associated with a significantly decreased risk (aOR: .63; 95% CI: .50-.80; P < .01); in multiparous women, maternal smoking was not associated with a statistically significant decreased risk of preeclampsia (aOR: 0.72; 95% CI: .51-1.02; P > .05). CONCLUSION: Maternal smoking is protective against preeclampsia. Understanding the underlying biologic mechanisms of this protective effect may advance our knowledge of the pathogenesis of preeclampsia.

Adolescent↗
PubMed1999

Impact of pregnancy-induced hypertension on fetal growth.

OBJECTIVE: The purpose of this study was to evaluate the effect of different types of pregnancy-induced hypertension on fetal growth. STUDY DESIGN: A retrospective cohort study was conducted on the basis of 16,936 births from January 1, 1989, through December 31, 1990, by means of data from a population-based perinatal database in Suzhou, China. Pregnancy-induced hypertension was classified as gestational hypertension, preeclampsia, or severe preeclampsia-eclampsia. Univariate and multivariate regression analyses were performed to examine the effect of the various types of pregnancy-induced hypertension on gestational age, preterm birth, birth weight, low birth weight, and intrauterine growth restriction. RESULTS: Gestation was 0.6 week shorter in women with severe preeclampsia than in normotensive women (P <.01). However, the risk of preterm birth was not increased with any classification of pregnancy-induced hypertension (for severe preeclampsia: adjusted odds ratio 1.75; 95% confidence interval, 0.88-3.47). After adjustment for duration of gestation and other confounders, preeclampsia and severe preeclampsia increased the risk of intrauterine growth restriction and low birth weight. The adjusted odds ratios of low birth weight were 2.65 (1.73-4.39) for preeclampsia and 2.53 (1.19-4.93) for severe preeclampsia. However, the risk of low birth weight was not increased significantly for gestational hypertension (adjusted odds ratio 1.56 [1.00-2.41]). CONCLUSION: Preeclampsia increases the risk of intrauterine growth restriction and low birth weight.

Adult↗
PubMed1999

Prostaglandin endoperoxide H synthase mRNA expression in the human amnion and decidua during pregnancy and in the amnion at preterm labour.

We have examined the expression of prostaglandin endoperoxide H synthase (PGHS) isoenzymes in the amnion and the decidua during gestation, and the abundance of PGHS mRNA in the amnion at idiopathic preterm labour. PGHS-1 and -2 mRNA abundance in the amnion, determined with ribonuclease protection assays, was significantly (P< 0.05) higher at term than earlier during pregnancy. In contrast, neither PGHS-1 and -2 mRNA values, nor PGHS-specific activity, measured with a cell-free assay, was different in the decidua at term as compared to earlier gestational ages. In individual term patients, PGHS-2 mRNA values in the amnion were positively correlated with PGHS-2 mRNA values in the chorion laeve. PGHS-1 and -2 mRNA abundance was higher (P < 0.05) in the amnion after idiopathic preterm labour than in the absence of labour at the same gestational age (28-35 weeks). Thus, PGHS-1 and -2 are induced in the amnion at term. Furthermore, amniotic PGHS-2 changes in co-ordination with PGHS-2 concentrations in the chorion laeve. PGHS is not induced in the decidua at term. Increased amniotic PGHS expression may contribute to the enhanced intrauterine prostaglandin synthesis before term labour. Both PGHS isoenzymes may participate in the increase of PGHS activity in the amnion at preterm birth.

Amnion↗
PubMed1999

Tyrosine kinase inhibitors block the glucocorticoid stimulation of prostaglandin endoperoxide H synthase expression in amnion cells.

Human amnion cells in primary culture respond to glucocorticoids in a characteristic fashion by the increased expression of the inducible prostaglandin endoperoxide H synthase isoenzyme, PGHS-2. Since PGHS-2 induction by agonists generally involves tyrosine kinases, we examined the possibility that the glucocorticoid stimulation of PGHS-2 in the amnion cells is tyrosine kinase dependent. PGHS-2 expression was stimulated in confluent, serum-starved amnion cells with dexamethasone, and the effect of the tyrosine kinase inhibitors herbimycin A and tyrphostins AG126, AG1288, and A1 on enzyme activity induction was determined. All four inhibitors blocked the increase of PGHS activity in a concentration-dependent manner with IC50 values of 0.077 +/- 0.05, 15.38 +/- 5.14, 20.91 +/- 3.1, and 29.77 +/- 8.21 microM, respectively (mean +/- SE, n = 4). Dexamethasone increased (approximately twofold) the tyrosine phosphorylation of 120-, 110-, and 77-kDa proteins in cell extracts, and herbimycin A selectively blocked the phosphorylation of the 110-kDa phosphoprotein. The stimulation of the steady-state level of PGHS-2 mRNA by dexamethasone was also inhibited by herbimycin A. These results suggest that glucocorticoids induce PGHS-2 expression in amnion cells with the involvement of tyrosine kinase(s). The role of tyrosine kinase dependent mechanisms in the control of amnion cell responsiveness to corticosteroids remains to be established.

Amnion↗
PubMed1999

Progesterone and prostaglandin H synthase-2 involvement in alcohol-induced preterm birth in mice.

BACKGROUND: Recently, an association between alcohol consumption during pregnancy and shortened gestational length has been reported, but the underlying mechanisms remain unknown. Progesterone (P4) and prostaglandins have been shown to play important roles in parturition in both human and animal models. Recently, it has been suggested that prostaglandin H synthase-2 (PGHS-2) is responsible for prostaglandin changes associated with term and preterm labor. It is possible that alcohol induces preterm birth by altering P4 or PGHS-2 levels. These studies were designed to determine the role of P4 and PGHS-2 in alcohol-induced preterm labor in mice. METHODS: Experiment 1: Pregnant dams treated with either vehicle or alcohol (6 g/kg, intragastrically) on gestational day (GD) 16 were killed at various times in gestation up to the time of delivery. Plasma P4 levels were measured by radioimmunoassay and uterine PGHS-2 mRNA expression was measured by Ribonuclease Protection Assay. Results indicated that alcohol treatment was associated with an earlier decline in plasma P4 levels and an earlier rise in uterine PGHS-2 mRNA levels during gestation. Experiment 2: Pregnant C57BL/6J females were treated with either P4 (2.0 mg, subcutaneously) or vehicle (sesame oil) 2 hr before receiving either 6 g/kg alcohol (intragastrically) or vehicle (isocaloric sucrose) on gestational day (GD) 16. Results indicate that P4 pretreatment effectively antagonized alcohol-induced preterm delivery. Experiment 3: On GD16, pregnant dams received either 100 mg/kg nimesulide (a specific PGHS-2 inhibitor) or vehicle (saline) subcutaneously, 2 hr before treatment with either 6 g/kg alcohol (given intragastrically) or isocaloric sucrose. Nimesulide was effective in antagonizing alcohol-induced preterm labor. CONCLUSIONS: Together, these data suggest that both P4 and PGHS-2 may play roles in alcohol-induced preterm birth.

Animals↗
PubMed1998

Regulation of prostaglandin H2 synthase-2 expression in primary human amnion cells by tyrosine kinase dependent mechanisms.

Prostaglandin H2 synthase (PGHS)-1 and PGHS-2 expression was examined in primary cultures of human amnion cells, an in vitro model of amnion tissue. Epidermal growth factor (EGF), the protein kinase C (PKC) activating phorbol ester TPA, and the protein phosphatase inhibitor, okadaic acid (OA), stimulated PGHS activity and the level of PGHS-2 mRNA, but did not affect the level of PGHS-1 mRNA. In situ hybridization suggested that the same population of cells responded to EGF, TPA and OA. Okadaic acid promoted PGHS activity independently of PKC. EGF stimulated the activity of extracellular signal-regulated protein kinase (Erk) and N-terminal c-Jun kinase (Jnk). OA increased Jnk activity but had no effect on Erk activity, while TPA had no influence on either Erk or Jnk activity. PD098059, a selective inhibitor of the Erk-activating kinase MEK, blocked the stimulation of PGHS expression by EGF, but did not decrease stimulation in response to OA. Herbimycin A, a tyrosine kinase inhibitor, suppressed the stimulation of PGHS activity and PGHS-2 mRNA abundance by all three stimulants, and blocked signalling via the Erk and Jnk mitogen-activated protein kinase pathways. Thus, growth factor stimulation, PKC activation and protein phosphatase inhibition induced the expression of PGHS-2 in primary amnion cells by distinct regulatory mechanisms involving tyrosine kinase(s). Tyrosine kinase inhibitors may constitute a new category of PGHS-2 inhibitors that act by blocking the expression of the enzyme.

Amnion↗
PubMed1998

The role of nitric oxide and metalloproteinases in the pathogenesis of hyperoxia-induced lung injury in newborn rats.

The effects of nitric oxide (NO) and metalloproteinases (MMP-2 and MMP-9) in the pathogenesis of hyperoxia-induced lung damage in newborn rats were examined. Three-day-old rat pups were subjected to hyperoxia (> or = 95% O2) or room air for 7 and 14 days. Some animals were treated with NG-L-nitro-L-arginine methyl ester (L-NAME, 10 mg kg(-1), s.c., daily). Histology, morphometry, oedema, Ca2+-dependent and -independent NO synthase (NOS) activities, expression of NOS isoforms and the activities of MMP-2 and MMP-9 were measured in lungs of hyperoxic and control animals. Exposure of rats to hyperoxia for 7 days resulted in alveolar sac injury characterized by the presence of cellular debris, red cell extravasation and inflammatory infiltration with mononuclear cells. Lung water content, epithelial, smooth muscle layers and total airway thickness was similar to controls. In contrast, exposure of rats to hyperoxia for 14 days resulted in lung oedema, inflammation and epithelial proliferation. Hyperoxia caused a decrease in Ca2+-dependent NOS activity, an effect that was associated with increased expression of eNOS protein. In control rats, Ca2+-dependent NOS activity and expression of eNOS were reduced at 14 days. Hyperoxia caused 10 fold increase in the activity of Ca2+-independent NOS that remained significantly elevated after 14 days of exposure to hyperoxia. The activity of this enzyme was unchanged in control rats. In lungs of hyperoxic rats, the immunoblot showed time-dependent, biphasic expression (peak at 7 days) of iNOS. The profile of expression of iNOS in control rats was similar. The activities of MMPs were increased in lungs of hyperoxic animals. The L-NAME treatment of hyperoxic animals reduced lung oedema and epithelial proliferation, but enhanced the activities of MMPs. L-NAME exerted no significant effects in control rats. It is concluded that increased generation of NO contributes to the pathogenesis of hyperoxia-induced lung damage in newborn rats.

Animals↗
PubMed1998

Prostaglandin endoperoxide H synthase (PGHS) activity and PGHS-1 and -2 messenger ribonucleic acid abundance in human chorion throughout gestation and with preterm labor.

Term and preterm parturition is associated with elevated intrauterine PG production. Although an increase of PG synthesis by the fetal membranes during term labor is well documented, there is little data available regarding the prostanoid production of these tissues at term, before the spontaneous onset of labor. In the present study, we determined the expression of PG H2 synthase (PGHS), the committing and rate-limiting enzyme of prostanoid biosynthesis, in the chorion laeve during gestation. Tissues were collected from 18 patients at term (37-41 weeks of gestation) and from 13 patients between 17 and 35 weeks of pregnancy. None of the patients were in labor. PGHS-specific activity and the abundance of messenger RNAs (mRNAs) encoding the two PGHS isoenzymes (the constitutive PGHS-1 and the inducible PGHS-2) were measured by a cell-free enzyme assay and specific ribonuclease protection assays, respectively. PGHS-specific activity as well as PGHS-1 and -2 mRNA levels were significantly (P < 0.01) higher at term before labor than earlier during gestation. Furthermore, PGHS activity at term exhibited significant positive correlation with PGHS-2 mRNA levels, but not with PGHS-1 mRNA levels. In situ hybridization indicated that the expression of both PGHS mRNAs increased in the epithelial and the mesenchymal cells of the amnion and the chorion laeve at term. Additionally, PGHS activity and mRNA levels were determined in the chorion laeve of a group of patients who gave birth spontaneously before term (30.6 +/- 1 weeks, mean +/- SEM, n = 5), and the values were compared with a group who delivered by cesarean section before labor at a similar gestational age (31.9 +/- 1.4 weeks, n = 5, P > 0.05 vs. the preterm labor group). None of the patients exhibited signs of genital tract infection. PGHS-specific activity and PGHS-1 and -2 mRNA levels were significantly higher in the preterm labor group than in the group who delivered preterm without labor. In situ hybridization suggested that the enhanced PGHS-1 and -2 mRNA expression occurred predominantly in the mesenchymal cells of the fetal membranes at preterm labor. Thus, PGHS-1 and -2 expression increases in the chorion laeve at term before labor, with PGHS-2 as the functionally prevalent isoform. This supports the possibility that PGs originating in the fetal membranes promote the onset of normal labor. Furthermore, preterm labor is associated with the elevated expression of the two PGHS isoenzymes in the chorion laeve. The maturation of the fetal membranes in preparation for term labor involves both the epithelial and the mesenchymal cells, whereas preterm labor is accompanied by the maturation of the mesenchymal tissue components, as reflected by PGHS expression. This difference may have implications in the early recognition of preterm labor.

Adult↗
PubMed1997

Prostaglandin-endoperoxide H synthase-2 expression and activity increases with term labor in human chorion.

We investigated the changes in prostaglandin-endoperoxide H synthase (PGHS) specific activity and the levels and distribution of PGHS-1 and PGHS-2 mRNA in chorion collected at term before the onset of labor (CS) and after term labor and delivery (SL). PGHS specific activity and PGHS-2 mRNA abundance were higher in chorion collected after SL compared with that obtained at CS (P < 0.001); there was no difference in the levels of PGHS-1 mRNA between CS and SI, tissues. The increase in PGHS specific activity at SL was significantly correlated with PGHS-2 mRNA expression (P < 0.05) but not with PGHS-1 mRNA levels. In situ hybridization indicated that the pervasiveness of staining for PGHS-1 mRNA throughout full-thickness membranes did not change with labor onset; however, a greater number of cells expressed PGHS-2 in SL tissues. Our results demonstrate a selective increase in PGHS-2 expression and activity in chorion trophoblasts and mesenchymal cells with term labor onset. These observations are similar to those concerning amnion and imply that a concerted mechanism may exist in the fetal membranes to induce PGHS-2 expression at labor.

Chorion↗
PubMed1997

Leukotrienes are indicated as mediators of hyperoxia-inhibited alveolarization in newborn rats.

We investigated the role of leukotrienes (LT) in hyperoxia-induced changes in lung parenchyma in neonatal rat pups. Rat pups were exposed to 21% O(2) (air) or >95% O(2) from days 4 to 14 after birth and were administered the 5-lipoxygenase (5-LO) inhibitor and LTD4 receptor antagonist Wy-50295, 5-LO-activating protein inhibitor MK-0591, or vehicle from days 3 to 14. All measurements were done on days 12-14. There was a significant (P < 0.05) increase in peptido-LT output from lung slices of animals exposed to O(2) compared with air-exposed animals. Both Wy-50295 and MK-0591 significantly lowered (P < 0.05) peptido-LT output in O(2)-exposed animals. The 6-ketoprostaglandin F(1alpha) output was increased similarly in both vehicle- and drug-treated O(2)-exposed animals. O(2) exposure also caused a significant increase in bronchoalveolar lavage fluid protein and extravascular lung water that could not be ameliorated by Wy-50295 or MK-0591. Hyperoxia-induced inhibition of alveolarization, indicated by a significantly (P < 0.05) lower parenchymal tissue density, specific internal surface area, and airspace perimeter-to-area ratio, and a significantly (P < 0.05) higher mean linear intercept and airspace unit volume than air-exposed animals, was prevented by both Wy-50295 and MK-0591. Although hyperoxia had no effect on septal thickness, Wy-50295 caused significant thickening in both air- and O(2)-exposed pups. Our studies provide evidence that hyperoxia-induced peptido-LT may mediate O(2)-induced inhibition of alveolarization and that this is not caused by an arachidonic acid shunt to cyclooxygenase.

Acute Disease↗
PubMed1996

Life-threatening effects of discontinuing inhaled nitric oxide in severe respiratory failure.

We present the effects of abrupt discontinuation of inhaled nitric oxide (NO) in four patients with severe hypoxemic respiratory failure. These patients ranged from 9 mo to 65 yr of age. In each patient, after the initiation of inhaled NO, a marginal, but immediate, beneficial effect on gas exchange and, when measured, a reduction in pulmonary artery pressures was noted. However, during attempts to discontinue inhaled NO, not only did these patients develop worsening oxygenation and recrudescence of pulmonary hypertension but, unexpectedly, these parameters were worse than the baseline values, leading to life-threatening hemodynamic instability. These effects reversed immediately after reinstitution of inhaled NO. The mechanism of this severe ¿rebound¿ in pulmonary hypertension after abrupt withdrawal of NO is unclear, but its existence emphasizes the need to avoid a substantial risk to these patients. Moreover, we believe that both unintentional and intentional termination of inhaled NO therapy may lead to life-threatening deterioration in gas exchange and circulatory hemodynamics that exceeds the initial therapeutic benefit.

Administration, Inhalation↗
PubMed1996

Lipid mediators in oxygen-induced airway remodeling and hyperresponsiveness in newborn rats.

We examined whether lipid mediators have a causal role in neonatal hyperoxia-induced lung damage, specifically, airway remodeling and hyperresponsiveness. Newborn rat pups were exposed to hyperoxia (> 95% O2 from Days 4 to 14 and 65% from Days 14 to 32) or normoxia. The 5-lipoxygenase inhibitor, LTD4 receptor antagonist, and inhibitor of platelet-activating factor synthesis, Wy-50,295 (30 mg/kg), or vehicle was administered daily from Days 3 to 32. Oxygen exposure significantly increased (p < 0.05) the production of one potential lipid mediator group, peptido-LTs, from explanted lung slices and large airways from 2-wk-old rat pups. At 4 wk, only the large airway tissue output showed significant elevation because of oxygen exposure. At both ages, Wy-50,295 significantly decreased (p < 0.05) the production of peptido-LTs in the lung and large airways of oxygen-exposed pups. Pulmonary function and airway wall morphometry were studied in 5-wk-old rat pups 2 to 3 d after oxygen exposure and drug administration ceased. The resistance change in response to methacholine (0 to 20 microg/kg body weight given intravenously) was greater (p < 0.02) in oxygen-exposed animals. Oxygen exposure caused significant (60% increase) smooth muscle thickening (p < 0.05). Wy-50,295 prevented the oxygen-induced airway hyperresponsiveness and smooth muscle thickening. We conclude that chronic hyperoxic exposure causes an increase in pulmonary production of at least one lipid mediator, peptido-LTs, from newborn rats and that this is associated with airway smooth muscle layer thickening and, consequently, airway hyperresponsiveness.

Animals↗
PubMed1996

Umbilical arterial blood flow and plasma prostaglandin E2 concentrations during arousal and breathing movements in fetal sheep.

To investigate the effects of lung distension and oxygenation on umbilical blood flow (UBF) and plasma prostaglandin E2 (PGE2) in relation to arousal and stimulation of breathing movements, we studied eight chronically instrumented, unanesthetized fetal sheep between 137 and 143 d of gestation. Electrocorticogram, electro-oculogram, nuchal and diaphragmatic electromyograms, arterial pH and blood gas tensions, Hb oxygen saturation, body temperature, and UBF were recorded in each fetus. Electrocorticogram, electro-oculogram, and nuchal electromyograms were used to define sleep states. No sooner than 4 d after surgery, fetal lungs were distended with 100% O2 or N2 in a randomized order via an in situ Y-endotracheal tube. PGE2 concentrations were analyzed by RIA. A significant increase in fetal arousal and stimulation of breathing during nonrapid eye movement sleep was observed during lung distension with O2 as compared with control periods and lung distension with nitrogen. In all sleep states, UBF significantly decreased during oxygenation as compared with the control values. However, no significant correlation was observed between the time of the onset of arousal and the decrease in UBF. Lung distension with N2 resulted in increased plasma PGE2 concentrations, whereas, no change was observed during oxygenation. Our data suggest that an increase in fetal partial pressure of arterial O2 leads to a decrease in UBF. However, the onset of arousal and stimulation of breathing during lung distension and oxygenation were not dependent on a decrease in plasma PGE2 concentrations.

Animals↗
PubMed1996

Regulation of prostaglandin endoperoxide H2 synthase in term human gestational tissues.

Increased production of prostaglandins by the gestational tissues is pivotal for the initiation and maintenance of human labour. A major source of prostaglandins in the pregnant human uterus is the amnion membrane, which synthesizes increased amounts of prostaglandin E2 (PGE2) at parturition. We have found that the activity of prostaglandin endoperoxide H2 synthase (PGHS), the enzyme catalyzing the committing step of prostanoid biosynthesis, increases significantly in the amnion at term and preterm labour, and also prior to the onset of clinical labour at term. Furthermore, the abundance of the mRNA encoding the inducible PGHS-2 isoenzyme was higher in the amnion after spontaneous delivery that before labour. The level of the constitutive PGHS-1 mRNA remained unchanged. In addition, we found a significant positive correlation between PGHS activity and the level of PGHS-2 mRNA, but not of PGHS-1 mRNA, in the individual tissue samples, also indicating that PGHS-2 was selectively induced in the amnion membrane at labour. The regulation of PGHS expression by agonists was studied using primary cultures of amnion cells. Glucocorticoid treatment enhanced the activity of PGHS and the level of PGHS-2 mRNA in the cultured cells, without affecting PGHS-1 mRNA abundance. The stimulation was glucocorticoid specific and was blocked by the glucocorticoid receptor antagonist RU486, suggesting that it was mediated by the glucocorticoid receptor. Inhibition of protein synthesis did not block the accumulation of PGHS-2 mRNA showing that the steroid acted directly, without inducing an intervening protein. Protein kinase C activator and protein phosphatase inhibitor compounds and epidermal growth factor also promoted PGHS-2 mRNA expression, demonstrating the involvement of protein kinase dependent mechanisms in PGHS-2 regulation. However, the role of these effectors in the in vivo control of PGHS-2 expression remains to be determined.

Amnion↗
PubMed1995

Control of human parturition.

Parturition is a process that is composed of five separate and distinct physiological components but which lead from one to the next and are, therefore, interdependent. As such, the regulation of myometrial contractility should not be examined in isolation but as part of this continuum. The initiation of labor begins with the biochemical events that result in the rupture of the fetal membranes, effacement of the cervix, and the switch from contractures to contractions. Because we have defined being in labor as the point at which contractions no longer revert to contractures, we suggest that labor is superimposed upon pregnancy in humans and nonhuman primates. There is no withdrawal or retreat from pregnancy, and no evidence exists that the concentrations or actions of progesterone diminish at term. Rather, the target tissues of labor are activated to perform their physiological functions, and these functions are initiated by stimulators. The best candidate for achieving activation is maternal estrogen, derived from fetal DHEAS, but major gaps in our knowledge of this process still exist. Prostaglandins are the most likely candidates as the stimulators of labor initiation, but close inspection of their precise roles also demands that clearer definition of their synthesis and actions be acquired. Coordination of and communication between the physiological events of labor motivates us to examine nontraditional mediators such as cytokines for their potential roles in the regulation of these events at normal term.

Animals↗
PubMed1995

Studies on glucocorticoid hormone actions in the regulation of human amnion PGHS.

The human amnion is an excellent model in which to study the regulation of the expression of prostaglandin endoperoxide H synthase-2 (PGHS-2) mRNA by glucocorticoids, as glucocorticoids can both stimulate and inhibit PGHS activity and can have their stimulatory effect reversed to an inhibitory one. Our studies suggest the presence of a glucocorticoid-induced inhibitory protein which affects the post-transcriptional activity of PGHS-2 mRNA. Glucocorticoid-induced expression of PGHS-2 mRNA may be dependent on protein phosphorylation.

Amnion↗