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Biomedical subjects

E Ostlund

Publications and source records attributed to E Ostlund.

At least 19 recordsLinked to original sources

Presence of CD30(+) and CD30L(+) cells in human placenta and soluble CD30 levels in cord blood are independent of maternal atopy.

The intrauterine environment is characterized by a Th2 dominance during pregnancy, a milieu that also promotes atopic allergy. The aim of this study was to compare the presence of CD30, a molecule associated with Th2 related disorders such as atopic allergy, and its ligand (CD30L) in placenta in order to investigate if the placenta environment differs between atopic and non-atopic women. Serum concentrations of soluble CD30 (sCD30) from the mothers and their newborns were also elucidated. There were no differences in the immunohistochemical expression of CD30 and CD30L in placenta from atopic (n=28) compared with non-atopic (n=37) women. CD30 was expressed on the decidual stromal cells alone, while CD30L, previously not described in placenta, was detected on macrophage-like HLA-DR(+) cells throughout the mesenchymal chorionic villi. Serum sCD30 in atopic mothers was significantly elevated compared with serum sCD30 in non-atopic mothers (P< 0.05), while sCD30 levels in cord blood were similar in both groups independently of maternal atopic heredity. We suggest that sCD30 in cord blood and CD30 expression by decidual cells may reflect the Th2 environment surrounding the fetus, and both CD30 and CD30L could have immune regulatory functions in placenta.

Decidua↗

Fibronectin is a marker for organ involvement and may reflect the severity of preeclampsia.

OBJECTIVE: We have studied whether plasma fibronectin is related to a rise in blood pressure during normal pregnancy, whether it can be used for the early prediction of preeclampsia, and whether plasma fibronectin is a marker for organ involvement in preeclampsia. STUDY DESIGN: Two hundred twenty-eight healthy pregnant nullipara women were examined prospectively during pregnancy. Analyses of fibronectin in plasma were performed in pregnancy weeks 16, 24, 28, 32, and 36. During the same period, 177 patients with suspected preeclampsia and/or intrauterine growth retardation (IUGR) were tested for plasma fibronectin, mainly in the third trimester. RESULTS: In the normal population of pregnant women (n=222/228), fibronectin levels were 0.35 +/- 0.06 g/L in pregnancy week 16 and 0.43 +/- 0.12 g/L in week 36. These levels showed a positive correlation to blood pressure elevation during pregnancy (r=0.21, p=0.006). The six patients in this group (n=6/228) who later developed preeclampsia had higher fibronectin values 0.42 +/- 0.07 g/L already in week 16 (p=0.023). In the population of women with suspected preeclampsia (preeclampsia, n=129; IUGR alone, n=17; hypertension or proteinuria during pregnancy, n=31), fibronectin values were significantly higher, 0.75 +/- 0.27 g/L than in the normal population. Patients with preeclampsia and laboratory signs of organ involvement (n=56) showed significantly higher fibronectin values (0.85 +/- 0.27 g/L) compared to preeclampsia without organ involvement (n=73) [0.76 +/- 0.22 g/L (p=0.03)]. CONCLUSION: Our data show that fibronectin is related to blood pressure in pregnancy. Fibronectin values in women who develop preeclampsia are elevated already in pregnancy week 16 and were higher in those with laboratory signs of organ involvement.

Adolescent↗

Decreased expression of thioredoxin and glutaredoxin in placentae from pregnancies with pre-eclampsia and intrauterine growth restriction.

Pre-eclampsia is one of the major contributors to perinatal morbidity. This study was performed to test a hypothesis which suggests that pre-eclampsia is associated with inadequate control by the thioredoxin system and other related reducing systems. Placental tissue from normal pregnancies (NC), severe pre-eclampsia with fetuses small for gestational age (SPE), mild pre-eclampsia with fetuses small for gestational age (MPE) and pregnancies with small fetuses for gestational age without any sign of pre-eclampsia (IUGR) was collected immediately after delivery. The mRNA levels for thioredoxin and glutaredoxin were determined using a solution hybridization method and the distribution of the proteins in a normal placenta was analysed by immunohistochemistry. Results showed that the thioredoxin mRNA level in the SPE group was decreased to one third of the level in the NC group. Also the IUGR group showed a significant decrease. The glutaredoxin mRNA level in the SPE group was one half of that seen in the NC group. There was significant correlation between the mRNA levels for thioredoxin and glutaredoxin, both in the normal and growth restricted pregnancies. We conclude that the thioredoxin and glutaredoxin reducing systems are affected in placenta from pregnancies with pre-eclampsia and/or growth restriction of fetuses, and that the decrease correlates to the severity of the condition.

Cell Nucleus↗

Fetal erythropoietin and endothelin-1: relation to hypoxia and intrauterine growth retardation.

BACKGROUND: We have examined whether endothelin-1 (ET-1) and erythropoietin (EPO) in amniotic fluid, and EPO in fetal serum obtained by cordocentesis from fetuses with signs of intrauterine growth retardation (IUGR), were correlated to fetal growth and/or chronic fetal hypoxia. METHODS: Amniotic fluid and fetal serum were obtained by cordocentesis from 28 fetuses suspected to have IUGR and subsequently analyzed for EPO and ET-1 by ELISA. These data were correlated to blood gas results and fetal/maternal parameters at delivery. RESULTS: A novel finding was that ET-1 correlated to PO2 in amniotic fluid. The average level of ET-1 in amniotic fluid was 48.3+/-4.7 pmol/L. The results also showed a correlation between EPO levels in amniotic fluid and EPO in fetal serum. Furthermore, EPO correlated weakly to birth weight at delivery. Children with the lowest birth weights had the highest EPO levels. High EPO values, similarly to ET-1, correlated to low pO2 values. The level of EPO in amniotic fluid was 8.0+/-1.6 mIU/ml and in cord blood 29.5+/-9.6 mIU/ml. CONCLUSIONS: The results indicate that ET-1 levels may be a marker for short-term hypoxia, but not for fetal growth, since ET-1 in amniotic fluid was correlated to PO2 at the time of cordocentesis, but not to birth weight. The results also indicate that EPO levels in amniotic fluid and in fetal cord serum are highly correlated, and thus both can be used as markers for fetal growth and chronic hypoxia before the onset of labor.

Adult↗

Termination of second trimester pregnancy with mifepristone and gemeprost. The clinical experience of 197 consecutive cases.

BACKGROUND: Earlier controlled clinical trials have demonstrated that combined treatment with the antiprogestagen, mifepristone and a suitable prostaglandin reduce the induction to abortion time in second trimester abortion. The aim of this study was to describe the results of the 197 consecutive second trimester terminations performed in routine clinical practice at our Department from 1996 to 1998. METHODS: The report is based on 197 consecutive second trimester abortions including live pregnancies and missed abortions, carried out in 192 women. The women were treated with 600 mg mifepristone followed 24 to 48 hours later by 1 mg gemeprost administered every 6 hours four times. If abortion had not occurred, 1 mg gemeprost was administered every 3 hours for the next 12 hours. After expulsion of the fetus a surgical evacuation of the uterus was routinely performed up to 18 weeks gestation and thereafter when needed. The induction to abortion time was defined as the interval between the insertion of the first gemeprost pessary and expulsion of the fetus. RESULTS: The median abortion time was 9.0 (1.4-40.5) hours for primigravidae and 7.2 (0-152.5) hours for multigravidae. The medium number of gemeprost pessaries to induce abortion was two and all except seven women aborted within 24 hours. Significantly more abortions occurred before 6, 7 and 8 hours in multigravidae than among primigravidae. The induction to abortion interval was also significantly shorter for nulliparous than for parous women. Except for one case of heavy bleeding, no serious complications occurred. CONCLUSION: The study confirms the efficacy and safety of mifepristone, together with gemeprost, for termination of second trimester pregnancy when routinely used in the clinic.

Abortifacient Agents, Nonsteroidal↗

Origin of the West Nile virus responsible for an outbreak of encephalitis in the northeastern United States.

In late summer 1999, an outbreak of human encephalitis occurred in the northeastern United States that was concurrent with extensive mortality in crows (Corvus species) as well as the deaths of several exotic birds at a zoological park in the same area. Complete genome sequencing of a flavivirus isolated from the brain of a dead Chilean flamingo (Phoenicopterus chilensis), together with partial sequence analysis of envelope glycoprotein (E-glycoprotein) genes amplified from several other species including mosquitoes and two fatal human cases, revealed that West Nile (WN) virus circulated in natural transmission cycles and was responsible for the human disease. Antigenic mapping with E-glycoprotein-specific monoclonal antibodies and E-glycoprotein phylogenetic analysis confirmed these viruses as WN. This North American WN virus was most closely related to a WN virus isolated from a dead goose in Israel in 1998.

Amino Acid Sequence↗

Examination for heat-labile, heat-stable, and Shiga-like toxins and for the eaeA gene in Escherichia coli isolates obtained from dogs dying with diarrhea: 122 cases (1992-1996).

OBJECTIVE: To examine Escherichia coli isolates obtained from dogs dying with diarrhea for heat-labile, heat-stable, and Shiga-like toxins and for the eaeA gene, which is associated with attaching and effacing lesions. DESIGN: Retrospective study. ANIMALS: 122 dogs. PROCEDURE: E coli isolates were tested by means of dot-blot hybridization of DNA extracts of cultured bacteria. Medical records of dogs from which E coli isolates with virulence genes had been isolated were examined, and histologic findings and evidence of intercurrent bacterial and viral infections were recorded. RESULTS: None of the E coli isolates obtained from these dogs produced heat-labile, heat-stable, or Shiga-like toxins; however, E coli isolates from 44 of 122 dogs were found to have the eaeA gene. Histologically, multifocal bacterial adherence to the epithelium and epithelial necrosis and detachment were seen in colonic specimens from 20 of 44 (45%) dogs. Escherichia coli was the sole pathogen identified in 15 of 44 (34%) dogs. Intercurrent pathogens, including canine parvovirus (n = 19), Clostridium perfringens (8), rotavirus (5), hookworms (3), coccidia (3), and Salmonella agona (1), were identified in the remaining 29 (66%) dogs. CLINICAL IMPLICATIONS: Attaching and effacing E coli can be a primary or secondary pathogen in dogs with diarrhea. Antibiotic treatment is indicated in dogs with diarrhea because of the possibility that it is primarily bacterial in origin and because, even if it is primarily viral in origin, there may be secondary bacterial infection.

Adhesins, Bacterial↗

Endothelin-induced contractions in placental arteries is mediated by both ETA- and ETB-receptors.

We have examined the contractile response to the vasoconstrictor endothelin-1 (ET-1) in uteroplacental arteries from normal pregnant women in the presence and absence of specific ET-receptor antagonists and agonists, and the vasodilator nitric oxide. Segments of placental arteries (n = 97) obtained from 37 placentas immediately after delivery were mounted in organ baths superfused with Krebs-Ringer solution at 37 degrees C. The tension was recorded isometrically and registered on a polygraph. We found that the placental artery segments responded to ET with a dose-dependent vasoconstriction. Half-maximal response was obtained at 2.6 x 10(-8) M. At 10(-7) M, the contractile response was 52% of the maximum KCl-response. The ET-1 induced contraction at 10(-7) M was inhibited by 74% after addition of the ETA-antagonist BQ-123 (10(-6) M), and by 58% by the ETB-antagonist BQ-788 (10(-6) M). Both BQ-123 and BQ-788 almost completely abolished the response to ET (10(-7) M). The selective ETB-agonist IRL-1620 also elicited vasoconstriction in the placental artery with a half maximal response at 8 x 10(-7) M. On a molar basis at 10(-7) M, the contraction by IRL-1620 as compared to ET was 30-fold lower. The contractile response of IRL-1620 (10(-6) M) was inhibited by 99% by BQ-788 (10(-6) M). After pre-contraction of the placental arteries with ET-1 (10(-7) M), the vessels relaxed in response to the nitric oxide donor, nitroglycerin (10(-6) M). The present results show that ET-1 contracts placental arteries through both ETA- and ETB-receptor activation. Nitric oxide (10(-6) M) was able to relax more than half of the initial ET-1 contraction, indicating that nitric oxide may be an important vasodilator in the placenta.

Adult↗

Plasma leptin in infants: relations to birth weight and weight loss.

BACKGROUND: The hormone leptin, produced in the adipose tissue, is involved in the regulation of body weight. The release of the hormone is increased in obese adults and decreased after fasting in human adults. This study investigated whether the plasma leptin level was related to the infant's birth weight and whether the level was reduced in connection with the physiological weight loss during the neonatal period. METHODS: We measured the plasma leptin level in cord blood from infants who were large for gestational age (LGA) (n = 15), small for gestational age (SGA) (n = 16), and appropriate for gestational age (AGA) (n = 38). AGA infants (n = 120), who were exclusively breastfed, were also studied during their first 4 postnatal days in a cross-sectional method. One blood sample was collected before breastfeeding from each infant. Plasma leptin concentrations were determined by radioimmunoassay. RESULTS: The median (range) concentration of leptin from cord blood was increased in LGA infants and decreased in SGA infants compared with the level in AGA infants. There was a positive correlation between the log of the plasma leptin level in cord blood and both the infant's birth weight (r = 0.76; n = 69) and the body mass index (r = 0.63; n = 69). The normal 3% to 6% weight reduction that occurs during the first 4 postnatal days was associated with a 26% decrease in the plasma leptin level in healthy breastfed infants. CONCLUSIONS: The plasma leptin level is highly correlated to the size of adipose tissue mass and decreases in connection with the initial physiological weight loss in newborn infants. These data provide evidence that leptin is highly related to the nutritional status already during the fetal and neonatal periods.

Adipose Tissue↗

Soluble fibrin in plasma as a sign of activated coagulation in patients with pregnancy complications.

BACKGROUND: Disseminated intravascular coagulation (DIC) is a frequently observed complication in pregnant women. The laboratory diagnosis of DIC is difficult but the development in the detection of circulating soluble fibrin has improved the possibility. METHODS: A number of pregnant women (n= 175) with obstetric complications e.g. preeclampsia, hypertension, intrauterine growth retardation (IUGR) and intrahepatic cholestasis was examined for plasma soluble fibrin and subjected to some routine hemostatic tests, mainly during the third trimester of pregnancy. RESULTS: Of these patients, 57 of 175 (33%) had an elevated concentration of soluble fibrin (above 23 nmol/L) as compared with a healthy group of women sampled in the third trimester. Eighteen patients (10%) had highly increased levels, above 100 nmol/L. In comparison, none of the 23 healthy, pregnant women investigated had a value above 40 nmol/L. CONCLUSIONS: Hemostatic abnormalities, including increased concentrations of soluble fibrin, are quite frequently observed in women with obstetric complications, most likely as a sign of a systemic activation of coagulation. Although a higher concentration of plasma soluble fibrin was observed in many of the women, no clear correlation to the outcome of the pregnancy was obtained. Whether or not plasma soluble fibrin is of any value, either diagnostically or the treatment of patients with pregnancy complications, remains to be shown.

Blood Coagulation Tests↗

Insulin-like growth factor I in fetal serum obtained by cordocentesis is correlated with intrauterine growth retardation.

We examined whether insulin-like growth factor-I (IGF-I) and one of its binding proteins (IGFBP-1) in fetal serum obtained by cordocentesis is correlated with intrauterine growth retardation (IUGR) and weight estimation by ultrasound. Cordocentesis sera from 27 fetuses suspected of having IUGR were analysed for IGF-I and IGFBP-1 by radioimmunoassay. The results showed that IGF-I concentrations were correlated significantly with birth weight (P < 0.001) and placenta weight (P < 0.05). Mean fetal concentrations of IGF-I were 38 +/- 18 microg/l. In patients (n = 11) with a weight deviation at delivery <-33%, IGF-I concentrations were 24.1 +/- 13.2 microg/l. IGFBP-1 was inversely correlated with birth weight (P < 0.006) and concentrations of IGF-I. Mean plasma concentrations of IGFBP-1 were 234.2 +/- 161.4 microg/l. Furthermore, IGF-I concentrations were correlated with the weight deviation estimated by ultrasonography at the time of cordocentesis (P < 0.007), as well as with the weight deviation at delivery (P < 0.0001). The actual weight deviation at delivery was correlated more strongly with fetal IGF-I concentrations than with the estimated weight deviation at cordocentesis. The lowest concentrations of IGF-I were found in patients with a weight deviation <-33%. Very low concentrations of IGF-I are thus associated with IUGR, indicating that IGF-I measured in fetal serum may increase the predictive value of ultrasonographic weight estimation.

Cordocentesis↗

Expression of protein kinase C isoforms in renal tissue.

PKC plays a central role for the regulation of renal function. PKC consists of a family of isoenzymes. By employing Northern blot techniques we have demonstrated that mRNA transcripts for the classical Ca(2+)-dependent, diacylglycerol-activated isoform alpha, the novel, Ca(2+)-independent isoform delta and the atypical isoform zeta are abundantly expressed in the rat kidney. The novel PKC-epsilon was weakly expressed. The classical PKCs beta I, beta II and gamma could not be detected. The mRNA expression of PKC-delta and -zeta increased with age. The intrarenal localization of PKC-alpha, -delta and -zeta isoforms were studied in the adult kidney using in situ hybridization. In the cortex, the PKC-alpha isoform showed the strongest hybridization signal. PKC alpha, delta and zeta were all distributed in the outer medulla. The PKC-alpha probe detected particularly strong signal in the outer stripe of the outer medulla. Western blot confirmed the presence of the PKC-alpha, -delta and -zeta enzymes in renal tissue. The results show cell-specific and developmentally-dependent expression of three types of PKC isoforms with different responses to diacylglycerol and calcium. The developmental increase of both PKC-delta and PKC-zeta suggests a specific role for these isoforms for the functional regulation of the mature kidney.

Animals↗

Endothelin-induced contractions in human placental blood vessels are enhanced in intrauterine growth retardation, and modulated by agents that regulate levels of intracellular calcium.

Endothelin-1 (ET-1) is a strongly vasoactive polypeptide that may be involved in the regulation of the uteroplacental blood flow. In the present study we have examined the contractile response to ET-1 in human placental arteries in the presence of several agents that interfere with storage of intracellular calcium, e.g. caffeine, ryanodine and thapsigargin. We have also compared the contractile response to ET-1 in normal pregnancies with that of patients with foetal intrauterine growth retardation (IUGR), a condition with reduced uteroplacental blood flow. We found that the response to ET-1 in the placental arteries from women with normal pregnancies was reduced by 20% in the absence of extracellular calcium. Caffeine relaxed the basal tone of the vessels and reduced the contractile response to ET-1 by 51%. Nifedipine in addition to caffeine resulted in a reduction of 70%. Ryanodine also reduced the tone. Thapsigargin had no effect on the placental arteries at lower concentrations, but gave a progressive and slow contraction at 10(-6) M. The ET-1 induced contraction in placental arteries from IUGR patients was 67% more potent than in placental arteries from women with normal pregnancies, 129% as compared with 77% of the maximal K(+)-induced contraction. We conclude that the ET-1-induced contractile response in the human placental artery is dependent on influx of extracellular calcium as well as mobilization of calcium from intracellular stores. An increased sensitivity to ET-1 in placental arteries may contribute to the reduced uteroplacental blood flow in intrauterine growth retardation.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Growth regulation of LLC-PK1 cells: lack of effect of Na(+)-loading.

To gain more information about the growth regulation of renal epithelial cells, we examined the growth stimulatory effect of serum and intracellular sodium in the renal epithelial cell line, LLC-PK1. In subconfluent LLC-PK1 cells serum-starved for 5 days and exposed to [3H]thymidine for 24 h, 22.9% of the cells synthesized DNA. Stimulation with 10% foetal calf serum (FCS) caused an almost three-fold increase in the fraction of labelled nuclei (62.2%). Serum-starved LLC-PK1 cells exposed to 10% FCS responded with an increased abundance of c-jun transcripts. The maximal expression of the c-jun transcripts occurred at 60 min and declined 120 min after serum stimulation. It has been suggested that an increase in Na+ influx plays a role in the growth regulation of renal epithelial cells. This prompted us to study the effect of intracellular Na+ loading on the growth response of LLC-PK1 cells. Serum-starved LLC-PK1 cells were incubated in a low K+ medium or exposed to Nystatin. Incubation in a low K+ medium or with Nystatin resulted in a marked increase in intracellular Na after only 5 min. A low K+ medium did not significantly influence the intracellular pH. No effect was observed on DNA synthesis or the abundance of c-jun transcripts in LLC-PK1 cells. Nor did Na+ loading enhance the growth stimulatory effect of serum. The results suggest that an increase in intracellular sodium does not directly regulate the growth of renal epithelial cells.

Animals↗

Very low cadmium concentrations stimulate DNA synthesis and cell growth.

Uptake of cadmium into cultured cells and its effects on cell growth and DNA synthesis are measured over a range of Cd concentrations of seven orders of magnitude. Cd uptake is found to be proportional to the external Cd concentration and to incubation time over a very broad range of concentrations. At least 200 mmol cadmium per kg dry weight of cells can be accumulated in this way, leading to exhaustion of the major intracellular Cd binding sites before cell death. On the other hand, very low cadmium concentrations down to 100 pM stimulate cell growth and DNA synthesis significantly. Stimulation is found in all three mammalian cell types examined: namely L6J1, a rat permanent myoblast cell line, LLC-PK1 porcine renal epithelial cells, and a primary rat chondrocyte culture. Cd acts as a cofactor with serum in L6J1 cultures, but is stimulatory only in serum-free cultures of chondrocytes. Stimulation occurs at Cd concentrations too low to result in a measurable induction of metallothionein. This might implicate the action of response amplifiers in the chain of events leading to Cd-stimulated DNA replication and cell growth.

Animals↗

Enhanced thrombin generation and fibrinolytic activity in normal pregnancy and the puerperium.

Blood coagulation and fibrinolytic inhibitors and the balance between and within the two systems were investigated in 26 normal pregnant women during pregnancy and the puerperium. The concentration of the coagulation inhibitors antithrombin and protein C remained within normal levels, whereas the mean level of free protein S showed a significant decrease from 0.26 U/mL in early pregnancy to 0.14 U/mL in week 35. At the same time, soluble fibrin levels increased from 9.2 to 13.4 nmol/L and thrombin-antithrombin complexes increased from 3.1 to 7.1 micrograms/L; both are indicators of thrombin activity. A concurrent increase in the levels of the fibrinolytic inhibitors plasminogen activator inhibitor-1 and -2 from 7.4 to 37.8 AU/mL and 31 to 160 micrograms/L, respectively, suggests a decrease in fibrinolytic activity. However, the levels of fibrin D-dimer, ie, fibrin split products, also increased in parallel from 91 to 198 micrograms/L, suggesting that fibrinolysis is present. Thus, a balance normally exists, which is probably why thrombotic events are rare during pregnancy.

Adult↗

Antenatal nonstress test in complicated and uncomplicated pregnancies in type-1-diabetic women.

111 pregnant women with type-1 diabetes were cared for at the Karolinska Hospital from 1979 to 1986. As routine fetal monitoring, a non-stress test (NST) was performed twice weekly from the 35th or 36th week of gestation to delivery. If pregnancy complications occurred, an NST was still used for fetal monitoring, but more frequently. The median gestational age at delivery was 270 days. The mean maternal blood glucose during the third trimester was 6.0 mmol/l. In 88 of the totally 111 women the only indication for an NST was the patient's diabetes. In this routinely monitored group, 2/88 patients had abnormal NSTs and cesarean sections were performed. The neonatal outcome was good in both cases. Twenty-three had such complications as pre-eclampsia or IUGR, and in these cases the frequency of an NST was individualized. Four of these 23 had abnormal NSTs leading to cesarean sections. There were no signs of asphyxia among these four infants. Thus, in diabetic pregnancies with a well-regulated blood glucose, intervention due to abnormal fetal monitoring is more associated with acute pregnancy complications than the diabetes per se. The results of this study suggest that antenatal NSTs twice a week from week 35-36 is sufficient in well blood-glucose regulated type-1-diabetic women with a well-regulated blood glucose. If pregnancy complications occur, the NST, in an individualized frequency, seems to be a safe way of fetal monitoring.

Blood Glucose↗