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Biomedical subjects

J Pirhonen

Publications and source records attributed to J Pirhonen.

At least 37 records · Page 2Linked to original sources

Activation of IFN-alpha, IFN-gamma, MxA, and IFN regulatory factor 1 genes in influenza A virus-infected human peripheral blood mononuclear cells.

Mononuclear blood cells have an important role in immunity as they produce different cytokines in response to microbial infections. We infected primary human mononuclear blood cells with a pathogenic influenza A virus (A/Beijing/353/89) and studied the activation of IFN-alpha, IFN-gamma, IRF-1, and MxA genes. IFN-alpha and IFN-gamma steady state mRNA levels peaked at 6 to 9 h after infection and declined rapidly thereafter. Only a modest (twofold) increase in IRF-1 mRNA was seen. MxA gene expression, normally strictly regulated by IFN-alpha/beta, had expression kinetics similar to those of IFN mRNA. Infection experiments done in the presence of cycloheximide showed that influenza virus infection could induce all genes studied in the absence of detectable protein synthesis. Pretreatment with IFN-alpha, but not with IFN-gamma, caused a dose-dependent inhibition of influenza virus replication in PBMC, and this inhibition correlated with increasing levels of MxA protein. Influenza virus replication was also inhibited in a stably transfected, MxA-expressing promonocytic U937 cell line. The results suggest that MxA protein significantly contributes to IFN-mediated host defence mechanisms against influenza A virus.

Antibodies, Monoclonal↗

Diagnosis of fetal anemia with Doppler ultrasound in the pregnancy complicated by maternal blood group immunization.

We investigated whether Doppler measurement of the fetal middle cerebral artery peak systolic velocity can be used to detect fetal anemia in pregnancies complicated by maternal blood group immunization. We first studied normal values for the middle cerebral artery peak systolic velocity in 135 fetuses (Group A), and also in 23 fetuses at risk for anemia who underwent 56 cordocenteses to assess the fetal hematocrit (Group B). A test to detect fetal anemia, based on the middle cerebral artery peak systolic velocity, was developed by using the data of the fetuses of Group A and Group B. Successively, the middle cerebral artery peak systolic velocity was prospectively determined in 16 fetuses at risk for anemia who underwent 42 cordocenteses (Group C) to assess the test developed, in a multicenter prospective fashion, by using the data of Group A and Group B. In the normal fetuses an exponential model expressed the increase of the middle cerebral artery peak systolic velocity values with advancing gestation. By using the data of the fetuses of Group A and Group B, four zones of anemia risk were identified. In Group C, none of the anemic fetuses had the middle cerebral artery peak velocity below the normal mean value, whereas all of the anemic fetuses had the peak velocity above the normal mean. The middle cerebral artery blood velocity increases with advancing gestation and is a non-invasive method of detecting anemia in pregnancies complicated by maternal blood group immunization.

Adult↗

The effect of nimesulide and naproxen on the uterine and ovarian arterial blood flow velocity. A Doppler study.

BACKGROUND: To measure the effect of oral naproxen and nimesulide treatments on the uterine and ovarian arterial blood flow velocity in both eumenorrheic and dysmenorrheic women. METHODS: The double-blind, placebo-controlled, study comprised six eumenorrheic women receiving either placebo or nimesulide (100 mg, single oral dose) during two consecutive cycles. Six women with moderate to severe dysmenorrhea were treated with placebo, nimesulide or naproxen (500 mg, single oral dose) during three consecutive cycles. Uterine impedance (pulsatile index, PI) was measured during the cycle day 1 at four different levels of the uterus and in the ovarian branch of the uterine artery at 0, 30, 60, and 120-140 min, with a color Doppler ultrasonograph for orientation and with pulsatile Doppler for recording waveforms. RESULTS: In the eumenorrheic women no significant changes were found with any treatment. In dysmenorrheic patients, nimesulide relieved symptoms and caused a decrease in uterine artery PI earlier than naproxen. Both treatments reduced the elevated uterine impedance in dysmenorrhea close to the normal level. When analyzing the PIs of the uterine artery at 4 different levels, the most prominent changes were observed in the fundus. The ovarian branch remained unaffected. CONCLUSIONS: Color Doppler ultrasonography and pulsatile Doppler are good methods for investigating disease- or drug-induced changes in uterine and ovarian blood flow velocities. Nimesulide induced a slightly faster and more complete decrease of the elevated uterine vascular resistance in dysmenorrhea, towards normal eumenorrheic levels, than naproxen. The fundal part of the uterus appears to be an important site of the pathogenesis in primary dysmenorrhea.

Adult↗

Invasive techniques for prenatal diagnosis: current concepts.

Recent dramatic advances have been made in our understanding of the genetic basis of diseases. One result will be an increase in the number of pregnant women considered potential candidates for prenatal diagnosis. At the same time, the invasive techniques by which fetal specimens for prenatal diagnosis are obtained have come under increasing scrutiny in the lay press. Practicing obstetricians must have sufficient knowledge of the benefits, risks, and limitations of these techniques to respond to patient inquiries. This article reviews the commonly used invasive prenatal diagnostic methods, including amniocentesis, chorionic villus sampling, and fetal blood sampling, as well as less widely available techniques, such as fetal skin and liver biopsies. Such relevant issues as indications, timing, and fetal risks are covered.

Amniocentesis↗

Role of N-glycosylation in the synthesis, dimerization and secretion of human interferon-gamma.

Human interferon-gamma (IFN-gamma) is a secretory glycoprotein, which has two potential N-linked glycosylation sites at positions Asn-25 and Asn-97 of its 143 amino acid long mature polypeptide chain. In order to understand the role of glycan residues in the synthesis and secretion of human IFN-gamma, both or either one of the potential N-linked glycosylation sites were mutated to Gln. The mutant and the wild-type (Wt) polypeptides were expressed in insect cells using a baculovirus vector. Elimination of the N-glycosylation site at position Asn-97 (N97Q) resulted in secreted protein yields of 70-90% as compared with the Wt production, whereas only 10-25% (N25Q) and 1-10% (N25Q,N97Q) levels of protein production was observed when the first or both sites were mutated, respectively. Although there was a difference between extracellular levels of produced protein, the kinetics of secretion was similar for all different IFN-gamma molecules. The Wt and the N-glycosylation site mutants were all secreted as dimers. The formation of biologically active dimers was more efficient for IFN-gamma polypeptides that had the intact glycosylation site at Asn-25 as compared with the other two mutant forms of IFN-gamma. The extent of dimerization correlated well with the observed secretion. The specific antiviral activity was of the same order (1 x 10(7) i.u./mg of protein) for the glycosylated IFN-gamma molecules, whereas it was slightly lower (0.5 x 10(7) i.u./mg of protein) for the unglycosylated mutant form.

Amino Acid Sequence↗

The effects of regional anaesthesia for caesarean section on maternal and fetal blood flow velocities measured by Doppler ultrasound.

We studied the effects of spinal anaesthesia (Group S), epidural anaesthesia (Group E), and combined spinal and epidural anaesthesia (Group SE), on maternal and fetal blood flow in 24 healthy parturients (n = 8/group) with uncomplicated singleton pregnancies using Doppler technique. Prior to the induction of anaesthesia, the patients were prehydrated with balanced electrolyte solution 15 ml.kg-1 over a period of 15 min. After the induction of regional anaesthesia, the systolic blood pressure was maintained within 15% limits of the preoperative values using prophylactic etilefrine infusion in Groups S and SE. The flow velocity waveforms of the maternal femoral artery, the main branch of the uterine artery (placental side), the foetal umbilical and middle cerebral arteries were recorded by Doppler technique before and after prehydration as well as after onset of T7 analgesia and the pulsatility indices (PI) were derived. Rapid intravenous prehydration had no effects on uteroplacental or fetal circulation as indicated by unaltered uterine, umbilical, and fetal middle cerebral artery PIs. After the onset of T7 analgesia, the uterine artery PI was increased in Group S indicating increased uterine vascular resistance while no changes occurred in Groups E and SE. No adverse effects were observed on the neonates as indicated by the Apgar score and the umbilical artery and vein acid-base status in any of the groups.

Adult↗

Postpartum diagnosis of placenta accreta with colour Doppler sonography.

Placenta accreta, although uncommon, is becoming an increasingly important clinical problem associated with placenta praevia and previous Caesarean section. A case report is presented of a woman with post partum partial placenta accreta diagnosed with color Doppler ultrasound. The aetiology, risk factors, clinical conditions, treatment and sonographic diagnosis are shortly reviewed.

Adult↗

Hydatidiform mole in a 56-year-old woman.

We present a rare case of a hydatidiform mole that occurred in a 56-year old woman. The main symptom was prolonged vaginal bleeding, and the gynaecological examination revealed a markedly enlarged uterus. Sonography revealed a 9 x 15 cm large cystic tumour in the pelvis. At operation, a suspicion of trophoblastic disease was arosen. Serum human chorion gonadotropin was still markedly elevated on the fifth postoperative day. After removal of the uterus and adnexae the recovery and the 3-year follow-up have been uneventful.

Antigens, Tumor-Associated, Carbohydrate↗

Comparison of intravaginal and two intracervical prostaglandin E2 gels in pre-induction of labour.

A randomized study was undertaken to compare the effect of vaginal (1 mg of dinoprostone/2.5 ml gel) and intracervical (0.5 mg of dinoprostone in 2.5 ml of two different vehicles) on induction of labor and perinatal outcome. Sixty women (n = 20/20/20) who presented with an unfavorable cervix and a specific indication for the induction of labor participated in the study. There were no significant differences between the groups with respect to maternal age, weight, parity, gestational length or Bishop scores before prostaglandin E2 preinduction. Labour was induced with prostaglandin gel alone in twenty-two patients and with oxytocin infusion on the following morning after gel application in seven patients; altogether the rate of successful induction was 48.3%. The rate of uterine hyperstimulation was 16.7% with most cases in the groups receiving intracervical prostaglandin E2. Neonatal asphyxia diagnosed with umbilical vein and artery blood gas analysis was seen in eleven neonates who were delivered by labor induced with prostaglandin gel alone (50%). Prostaglandin pre-induction decreases the need for Cesarean sections in complicated pregnancies, but because of the risk of uterine hyperstimulation and neonatal asphyxia prostaglandins should be used only with specific indications.

Administration, Intravaginal↗

The fetal cardiovascular function in chronic placental insufficiency is different from experimental hypoxia.

Ten mothers at normal term pregnancy were rendered mildly hypoxic by allowing them to breathe a gas mixture of 10% oxygen and 90% nitrogen. The fetuses were studied with Doppler ultrasound and computer assisted cardiotocography. There was vasodilatation in the cerebral vasculature while the utero-placental blood flow decreased. No changes in fetal haemodynamics occurred. The fetal heart rate was correlated inversely to the heart rate variation. There was a positive correlation between the heart rate variation and the umbilical flow velocity waveform index. In a group of 30 subjects with severe pre-eclampsia and/or severe intrauterine growth retardation, the fetal heart rate variation was inversely correlated to the umbilical blood flow. Hence, the study shows a clear physiological difference in fetal heart function during short-term hypoxia compared to that during long term placental insufficiency.

Adult↗

Diagnostic transabdominal amnioinfusion in a case of anhydramnion and fetal kidney dysplasia.

Diagnostic transabdominal amnioinfusion was performed at 32 weeks of gestation in a case of anhydramnion. Before saline infusion, no exact fetal structures could be identified by sonography. Also, there was a total diastolic block in the fetal aorta (FA) and umbilical artery (UA). After infusion of 270ml of saline, the diastolic blocks in the FA and UA disappeared, and, after another infusion of 410ml of saline, severe fetal congenital kidney abnormalities were identified. Transabdominal amnioinfusion is a practical aid to fetal sonography in severe oligohydramnion and anhydramnion.

Adult↗

Flow velocity waveforms in the uterine artery in high risk pregnancies.

Blood flow velocity investigations by applying Doppler method have emerged as a useful tool in obstetrics and gynaecology. The final role of the method is still to be established. Thus far, the umbilical artery Doppler indices have been preferred to the utero-placental indices. We have analysed the Doppler indices from the main branch of uterine artery in 280 women with singleton pregnancy in the third trimester. While fetal blood flow velocities in the cerebral arteries or in the umbilical artery are still unchanged, the increase in the uterine artery resistance may serve as an early indicator of the increased risk to the fetus.

Adult↗

Effect of carbohydrates on the pharmacokinetics of human interferon-gamma.

Human interferon-gamma (IFN-gamma) has two N-linked glycosylation sites at positions 25 and 97 of the 143-amino-acid-long secretory form. To study the role of glycan residues in the pharmacokinetics of IFN-gamma, we produced recombinant IFN-gamma molecules lacking either one or both of the glycosylation sites (Asn mutated to Gln) by baculovirus expression in insect cells. In addition, we produced the fully glycosylated forms both in insect cells and in human leukocyte cultures. Two million units of each IFN were injected intravenously or intramuscularly into rabbits. The glycosylated IFN-gamma molecules from the insect cells were rapidly eliminated from the blood. This is probably due to the fact that their oligosaccharides are of a high mannose type that are rapidly taken up by the liver. The unglycosylated IFN-gamma persisted longer in the blood than the glycosylated recombinant forms. However, the natural IFN-gamma exhibited the longest survival in the blood. The results emphasize the importance of the carbohydrate groups in human IFN-gamma to its pharmacokinetic properties.

Animals↗

Differential inactivation of interferons by a protease from human granulocytes.

Human leukocyte suspensions produced interferon-alpha (IFN-alpha) without induction during incubation at 37 degrees C. The highest titers were obtained at about 30 million cells/ml. The best yields, approximately 2 IU per 10(6) cells, were achieved in medium with or without albumin; serum inhibited the production. The uninduced IFN-alpha peaked at 24 h. The titers dropped on further incubation due to release of a protease from polymorphonuclear cells. The protease inactivated all tested human class I IFNs, but recombinant IFN-alpha 1 was clearly more resistant to the enzyme than rIFN-alpha 2. Human IFNs-gamma from different sources exhibited striking differences in their sensitivity to the protease. Glycosylated natural IFN-gamma from human leukocytes and glycosylated rIFN-gamma from CHO cells were relatively resistant, whereas unglycosylated rIFN-gamma from Escherichia coli was rapidly degraded by the protease. The protease was inhibited by PMSF and by greater than or equal to 1% human or fetal bovine serum but not by EDTA or less than or equal to 1% human albumin. Its optimum pH was between 7 and 8. It was resistant to treatment for 30 min at 56 degrees C.

Cells, Cultured↗

Doppler flow measurement of uterine and umbilical arteries in heat stress during late pregnancy.

The effect of a moderate heat stress (20 minutes 70 degrees C) on uterine and umbilical artery blood flow was studied by continuous-wave Doppler ultrasound in 17 women 36 to 37 weeks pregnant. Maternal heart rate increased on average by 26 beats/minute. Maternal arterial blood pressure did not change during the heat stress but declined slightly immediately after. The fetal heart rate increased on average by 14 beats/minute by the end of the exposure. The variability of fetal heart rate was normal in each subject during the whole experiment and only one subject had a nonreactive tracing during the heat stress, which returned to normal during the recovery period. The ratio of the systolic to diastolic velocity in the uterine artery did not change significantly. Only two subjects had a marked increase in uterine artery vascular resistance; they had concomitantly a significant fall in the arterial blood pressure. Still, there was no change in umbilical artery blood flow. The fetuses of healthy pregnant women are not compromised during or after moderate thermal stress.

Adult↗