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R Austgulen

Publications and source records attributed to R Austgulen.

At least 37 records · Page 2Linked to original sources
PubMed1996

Soluble tumor necrosis factor receptors and CA 125 in serum as markers for epithelial ovarian cancer.

Increased serum levels of soluble tumor necrosis factor receptors (TNFRs) have been observed in patients with various types of malignancies. For the monitoring of ovarian cancer during treatment serum TNFRs have given information equivalent or better than that obtained by CA 125. In this study, we compared the diagnostic value of TNFRs and CA 125 in discriminating ovarian cancer from benign pelvic masses. Preoperative serum levels of p55 and p75, two distinct types of TNFRs, and that of CA 125 were determined by immunoassays in 45 patients with malignant and 27 patients with benign tumors operated consecutively. A group of 26 healthy women served as controls. For each of the three markers the group with ovarian cancer showed significantly higher values than the group with benign masses (p < 0.01). The rate of marker elevation correlated with ovarian cancer staging. Using upper cutoff levels of 2.0 ng/ml (p55), 4.3 ng/ml (p75) and 20 U/ml (CA 125), the calculated sensitivities were 58% (p55), 16% (p75) and 82% (CA 125). The specificities were 89% (p55), 96% (p75) and 85% (CA 125), respectively. Adding p55 to CA 125 did not increase the diagnostic values compared to using the CA 125 test alone. Our data confirm the superiority of serum CA 125 as a marker for discriminating ovarian cancer from benign pelvic masses. The p75 marker was found to be of no value, and for the detection of early stage ovarian cancer the sensitivity of p55 was too low to be of clinical importance.

Adult↗
PubMed1996

Detection of soluble receptors for tumor necrosis factor, interleukin-2 and interleukin-6 in retroplacental serum from normal pregnant women.

Soluble cytokine receptors (R) may regulate the activities of the cytokines present. We have studied the occurrence of soluble receptors for the cytokines tumor necrosis factor (TNF), interleukin-2 (IL-2) and interleukin-6 (IL-6) in normal pregnant women. Levels of TNFR and IL-2R were higher in retroplacental serum (RPS) than in the corresponding peripheral serum (PS) samples. TNFR, but neither IL-2R nor IL-6R, concentrations in PS from pregnant women were elevated compared to that in nonpregnant women. RPS inhibited TNF-mediated cytotoxicity, with the inhibitory effect being reduced after the removal of 55 kD TNFR from RPS. Our data reveal that soluble cytokine receptors are present in RPS and may contribute to the adjustment of intrauterine cytokine activities during pregnancy.

Antigens, CD↗
PubMed1995

Comparison between soluble tumor necrosis factor receptors and CA125 in peritoneal fluids as a marker for epithelial ovarian cancer.

The levels of the soluble forms of the membrane-bound receptor for tumor necrosis factor (TNF), p55 and p75, were assessed in peritoneal fluid samples from 50 patients with ovarian cancer, from 20 patients operated for benign pelvic masses, and from 26 healthy women undergoing laparoscopy. The 95% cutoff for normal levels were 14.0 and 5.2 ng/ml for p55 and p75, respectively. In patients with active ovarian cancer, elevated levels of p55 and p75 were found in 54 (p55) and 84% (p75) of the patients, and elevated levels were seen in all histologic types. The levels correlated with peritoneal fluid quantity and with stage of disease. Among 20 patients operated for benign pelvic masses, 1 patient had elevated p55 and 8 patients (40%) had elevated p75. The concentration of CA125 in peritoneal fluids showed a 95% cutoff value in healthy individuals of 8.950 U/ml; and elevated CA125 levels were found in 7 patients with ovarian cancer (14%) and in none of the patients with benign masses. The results indicate that in peritoneal fluid, measurement of soluble TNF receptors, and particularly of p75, has an increased sensitivity and accuracy over CA125 in distinguishing ovarian cancer from benign pelvic masses.

Adult↗
PubMed1995

Detection of cytokines (interleukin-1, interleukin-6, transforming growth factor-beta) and soluble tumour necrosis factor receptors in embryo culture fluids during in-vitro fertilization.

Several lines of evidence suggest that a number of immunoactive cytokines participate in early reproductive events such as implantation and placental development. Furthermore, cytokines may influence embryo growth and differentiation. In the present study, the production of tumour necrosis factor (TNF), interleukin-1 (IL1), interleukin-6 (IL6) and transforming growth factor-beta (TGF beta) during the first 48 h after oocyte retrieval during in-vitro fertilization was investigated. In addition, the question was raised whether soluble receptors may contribute to cytokine activity regulation in early reproduction, and concentrations of TNF and IL6 receptors in culture media were determined. Finally, an investigation of whether any association exists between cytokine concentrations and embryo morphology was performed. Media from 256 embryos were analysed. IL1, IL6 and TGF beta were produced during the 48 h culture period, whereas no TNF was detected. Levels of IL1 and IL6 were significantly higher in media from the first 24 h culture period than from the second period, whereas TGF beta concentrations in supernatants from the two observation periods did not differ. IL6 receptors were not detected, whereas TNF receptors (p75) appeared in media from the 24-48 h culture period. Granulosa, cumulus and sperm cells are potential sources of cytokine production, especially during the first 24 h period. The contribution of the embryo to cytokine/cytokine receptor production remains an open question. No significant correlation was observed between cytokine/cytokine receptor concentrations and embryo morphological score.

Culture Media, Conditioned↗
PubMed1995

Interleukin-6, tumour necrosis factor and soluble tumour necrosis factor receptors in women with pre-eclampsia.

OBJECTIVES: Generalised maternal endothelial cell dysfunction appears to be an underlying problem in pre-eclampsia presumed to be caused, directly or indirectly, by one or more circulating factors derived from the placenta. Recently it has been suggested that tumour necrosis factor (TNF) may play an important role in pre-eclampsia and contribute to endothelial activation. This study was designed to investigate this proposal. DESIGN: Plasma TNF-alpha, IL-6 and both forms of soluble TNF receptors (p55 and p75 TNF-R) have been measured by ELISA in 31 pre-eclamptic patients and 31 pregnant controls matched for age, parity and gestational age. RESULTS: Levels of IL-6, TNF-alpha and soluble TNF-R (p55 and p75) were significantly higher in pre-eclamptic patients, compared with age and gestation matched controls with a wide variation in levels between pre-eclamptic individuals. There was a correlation between levels of IL-6 and TNF or TNF-R and between TNF and TNF-R levels. However, when the pre-eclamptic patients were subdivided on the basis of the severity of their disease, the median values of plasma concentrations of IL-6, TNF-alpha and TNF-R were all higher in the group with lower platelet counts. CONCLUSIONS: These new findings are consistent with the concept that the maternal syndrome of pre-eclampsia is associated with endothelial dysfunction and provide evidence that at least part of this dysfunction could arise from excessive release of TNF-alpha into the circulation.

Adult↗
PubMed1995

Soluble tumor necrosis factor receptor in serum and urine throughout normal pregnancy and at delivery.

PROBLEM: To determine the concentration of the two soluble tumor necrosis factor receptors (sTNFR), sp55 and sp75, in healthy pregnant women. METHOD: Serum and urine samples were longitudinally collected from a group of pregnant women (N = 53) five times throughout pregnancy. Maternal and umbilical sera were obtained from some of the deliveries (N = 31). The samples were analysed using ELISA based on two monoclonal antibodies (IV4E and 3H5) against the soluble tumor necrosis factor receptors (sp55 and sp75). RESULTS: Serum concentration of sp55 and sp75 were increased in pregnant women compared to that of nonpregnant controls. Concentration of both sTNFRs increased towards term. Labor was associated with further increase of sp55. Concentrations of sp55 and sp75 in umbilical serum were significantly higher than those of maternal serum. Significant correlations were observed between maternal and umbilical sTNFR concentrations. CONCLUSIONS: The current study suggests that pregnancy is associated with an activation of mechanisms regulating the biological activities of TNF.

Female↗
PubMed1995

Interleukin-1, interleukin-6 and tumor necrosis factor at delivery in preeclamptic disorders.

BACKGROUND: To examine if preeclamptic disorders lead to altered concentrations of tumor necrosis factor, interleukin-1 and interleukin-6 at delivery compared to normal pregnancy. METHODS: Amniotic fluid, placenta, maternal and cord serum were collected at delivery by cesarean section or spontaneous labor. Samples were retrieved from 53 women with normal pregnancy, 54 with preeclamptic disorders and 15 who delivered a small for gestational neonate of unknown cause. Cytokines were measured by bioassays. Statistics were performed with nonparametric tests. RESULTS: Interleukin-1 in amniotic fluid tended to be lower with preeclamptic disorders than in normal pregnancy irrespective of labor. There was an increase in amniotic fluid tumor necrosis factor, interleukin-1 and interleukin-6 with onset of labor in preeclamptic disorders just as in normal pregnancy. There was a similar increase in interleukin-6 in cord and maternal serum in the same groups, even if concentration of interleukin-6 in cord serum in labor of preeclamptic disorders was lower than in normal pregnancy. CONCLUSIONS: No major differences were seen in concentrations of interleukin-1, interleukin-6 and tumor necrosis factor in amniotic fluid, placenta, maternal or cord serum at delivery with preeclamptic disorders compared to normal pregnancy.

Adult↗
PubMed1994

[Normal labor. Is it induced as a result of subtle intrauterine inflammatory reactions?].

The present study was conducted in order to test the hypothesis the elevated cytokine levels in amniotic fluid from normal deliveries may be generated by a subclinical inflammatory response in intrauterine tissue. Specimens were collected from 38 women with normal deliveries. The levels of tumour necrosis factor, IL1 and IL6 in amniotic fluid samples correlated with the extent of inflammatory cell infiltration in specimens of the foetal membranes, placenta and umbilical cord. Tumour necrosis factor, IL1 and IL6 are generally produced as part of the inflammatory reaction and stimulate synthesis of prostaglandin. Thus a subclinical, intrauterine inflammatory response may play a role in initiation of normal parturition at term.

Amniotic Fluid↗
PubMed1994

Cytokine levels in amniotic fluid and inflammatory changes in the placenta from normal deliveries at term.

Cytokine levels in amniotic fluid have been shown to increase towards term in normal pregnancies, and may play a regulatory role in parturition by stimulating the local production of prostaglandins. The work reported in the present paper was conducted in order to test the hypothesis that the increased cytokine levels may be induced by a subclinical inflammatory reaction in intrauterine tissues. The concentrations of tumor necrosis factor (TNF), interleukin 1 (IL-1), interleukin 2 (IL-2) and interleukin 6 (IL-6) were determined in samples of amniotic fluid from 38 women in delivery at term, after a clinically normal pregnancy. In 33 of the cases, tissue material was available for histological examination. In these, the extent of inflammatory cell infiltration was assessed in the fetal membranes, placenta and umbilical cord. A close interrelation was observed between the levels of the mediators typically released during inflammatory processes (TNF, IL-1, IL-6). Frank chorioamnionitis was not found in any of the histological specimens, although most placentae showed varying degrees of granulocyte infiltration in the fibrin layer under the chorion, sometimes also in the chorionic membrane. The degree of such leukocytic infiltration correlated positively with the levels of TNF, IL-1 and IL-6. These findings lend support to the hypothesis that a low-level inflammatory process may be a normal occurrence in the term placenta, and that this process may induce the production of cytokines, which, in turn, may play a role in the regulation of parturition. Such inflammation could be due to exposure of the fetal membranes to microbial material from the vagina, as the cervix dilates towards term.

Amniotic Fluid↗
PubMed1994

Increased levels of cytokines and cytokine activity modifiers in normal pregnancy.

Accumulating evidence suggests that cytokines are major participants in human reproduction. Cytokines may have beneficial or negative influence on pregnancy outcome, depending on the cytokine level present. Thus, successful reproduction appears to depend on a tight regulation of cytokine activities. The present study raised the question whether normal pregnancy is associated with an activation of native cytokine buffer mechanisms. Soluble interleukin 6 receptors (IL-6Rs) and soluble interleukin 1 receptor antagonists (IL-1RAs) may modify the activity of IL-6 and IL-1, respectively. The production of soluble IL-6R and IL-1RA in pregnancy was studied by assessing the IL-6R and IL-1RA concentrations in serum samples from healthy pregnant women at different gestational ages. At delivery, both maternal and umbilical blood was obtained. Concentrations of IL-6 and IL-1 in the samples were determined to study the influence of cytokines on the activity level of the corresponding buffer mechanism. Serum levels of both IL-6R and IL-1RA were increased in pregnant women, as were levels of IL-6 and IL-1. Cytokine levels did not demonstrate a significant correlation with the concentration of the corresponding activity modifier. IL-1RA and IL-6 increased with gestational age and with labor activity. A significant correlation was observed between the levels of IL-6 and IL-1RA.

Female↗
PubMed1994

Immunohistologic detection of non-pancreatic phospholipase A2 (type II) in human placenta and its possible involvement in normal parturition at term.

Placenta is one of the richest sources of non-pancreatic phospholipase A2 (npPLA2) (type II) in the human body, and the enzyme is the key enzyme releasing unsaturated fatty acids from membrane phospholipids. Prostaglandins (PGs) play a critical role in the initiation and progression of parturition. Cytokines are presumed to play a central role in the initiation of normal labor at term, and cytokines are also found to regulate both synthesis and secretion of npPLA2 enzyme. In an attempt to resolve the physiologic function of the npPLA2 enzyme in placental tissue, immunohistologic localization and enzymatic activity measurements of npPLA2 enzyme were performed. NpPLA2 protein was detected in vascular smooth muscle, endothelial cells and connective tissue cells in placenta and umbilical cord, and the protein was weakly stained in trophoblast cells in placenta. Enzymatic activity was not increased in sera from mother nor child compared to sera from healthy individuals, but the activity in amniotic fluid was considerably higher. Our findings support the candidacy for npPLA2 in enzymatic arachidonic acid release from foetal membranes.

Amniotic Fluid↗
PubMed1993

Tumor necrosis factor, interleukin-1, and interleukin-6 in normal human pregnancy.

OBJECTIVE: Our purpose was to investigate the cytokines, tumor necrosis factor, interleukin-1, and interleukin-6 in normal human pregnancy and labor. STUDY DESIGN: Bioassays were used to measure these factors in extraembryonic coelomic fluid, amniotic fluid, placenta, and maternal and cord serum. RESULTS: Little or no tumor necrosis factor, interleukin-1, or interleukin-6 was found in coelomic fluid or amniotic fluid in the first trimester. Interleukin-6 appeared in second-trimester amniotic fluid. At term tumor necrosis factor was present (median 17 pg/ml) and increased with the onset of labor (median 58 pg/ml), as did interleukin-1 (median 188 to 680 pg/ml) and interleukin-6 (median 399 to 4800 pg/ml). Maternal serum interleukin-6 increased during pregnancy with a further increment with the onset of labor. Cord interleukin-6 also increased with labor but at a lower level. CONCLUSION: The cytokines tumor necrosis factor, interleukin-1, and interleukin-6 may play a role in the onset of normal labor.

Amniotic Fluid↗
PubMed1993

High concentrations of the soluble p55 tumour necrosis factor receptor in human seminal plasma.

Soluble TNFRs (tumour necrosis factor receptors) inhibit in-vivo and in-vitro bioactivities of TNF, and thus the secretion of soluble TNFRs could be a physiological principle to attenuate the bioactivities of TNF. Two types of TNFR have been identified and both forms can be released from cells. In this study, soluble TNFRs in seminal plasma from three groups of men were analysed: from men with normal semen quality (n = 32), with reduced semen quality (n = 7) and vasectomized men (n = 3). Sensitive and specific enzyme-linked immunosorbent assays were utilized to detect soluble TNFRs in seminal plasma, based on capture antibodies directed against non-TNF-binding sites of the TNFRs and digoxigenin (DIG)-labelled TNF. The mean +/- standard deviation levels of p55 TNFR were 56.4 +/- 20, 64.4 +/- 17 and 45.4 +/- 5 ng/ml in the three groups, respectively. The concentration of p75 TNFR was < 1 ng/ml in all groups. The results suggest an exclusive existence of high amounts of the soluble p55 TNFR in seminal plasma. Seminal plasma from vasectomized men contained p55 TNFR at approximately the same levels as the specimen from the two other groups, indicating that the source of p55 TNFR is not the testis but rather some tissue more distal in the male genital tract, such as the prostate or the seminal vesicles. The soluble p55 TNFR was purified from human seminal plasma, using affinity and gel filtration chromatography. Further characterization of the purified p55 revealed a protein with a molecular weight of approximately 22 kDa, both under reducing and non-reducing conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, Affinity↗
PubMed1993

Increased levels of soluble tumor necrosis factor-alpha receptors in serum from pregnant women and in serum and urine samples from newborns.

Secretion of soluble cytokine receptors has been suggested as a mechanism of regulating cytokine activity in vivo. In this study, the presence of soluble receptors for tumor necrosis factor-alpha (TNF-alpha) in serum samples from pregnant women and newborn babies was examined by using TNF-alpha receptor-specific immunoassays. Serum from pregnant women contained the 55-kD TNF-alpha receptor p55 [6.4 micrograms/L, interquartile range, i.e. the difference between the 25th and 75th percentile, (IQR) 7.2 micrograms/L], whereas p55 was not detected in control sera from nonpregnant, fertile women. The levels of p55 were also elevated in serum from newborns (3.2 micrograms/L, IQR 0.7 micrograms/L). Furthermore, first-voided urine from newborns contained high levels of p55 (44.6 micrograms/L, IQR 96.6 micrograms/L). The concentration of p55 in the neonatal period was significantly higher than that of children later in childhood (p < 0.05). The concentration of p55 was 7.3 micrograms/L, IQR 13.8 micrograms/L, in urine samples from a group of preschool children (1 mo < age < 5 y) and 6.9 micrograms/L, IQR 2.9 micrograms/L, in urine samples from children in a higher age group (5 y < age < 10 y). The concentration of the 75-kD TNF-alpha receptor in urine did not differ significantly between the different age groups studied. The elevated p55 serum levels of pregnant women and neonates are suggestive of a pregnancy-associated release of soluble receptors. The high concentration of p55 in neonatal urine may reflect a postpartum elimination of soluble receptors shed during pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗
PubMed1993

Soluble receptors for tumor necrosis factor: occurrence in association with normal delivery at term.

OBJECTIVE: To compare levels of tumor necrosis factor (TNF) and interleukin 1 (IL-1) and 6 (IL-6) with levels of the soluble receptors for TNF in maternal and neonatal urine and amniotic fluid (AF). METHODS: Levels of soluble TNF receptors (p55, p75) in AF and urine from 21 women and their newborns were measured by immunoassay. The amniotic concentrations of IL-1 and IL-6 were assessed by biologic assays, whereas an immunoassay was used to measure TNF levels. The comparison between receptor concentrations in different compartments was performed by one-way analysis of variance, and Student t test was used to compare pairs of groups. Correlation studies were performed when indicated. RESULTS: A high correlation was observed between the concentrations of p55 and p75 in all compartments. The concentration of p55 in AF was significantly higher than that in both maternal and neonatal urine, but the correlation between TNF receptor concentrations in the AF samples and the concomitant levels of cytokines was not statistically significant. CONCLUSION: The high concentration of receptors in the AF compared to those of other biologic compartments suggests that the pregnancy-associated increased receptor shedding takes place in intrauterine tissues. Physiologic levels of cytokines, such as those accompanying normal delivery at term, did not seem to influence the soluble TNF receptor release.

Amniotic Fluid↗
PubMed1992

[Secretion of soluble receptors for tumor necrosis factor. An immunologic buffer mechanism during normal pregnancy?].

High concentrations of tumour necrosis factor may threaten the well-being of the foetus. Secretion of soluble cytokine receptors has been suggested as a mechanism for regulating cytokine activity in vivo. In this study pregnancy-related materials were examined for the presence of soluble receptors (p55 and p75) for tumour necrosis factor. In contrast to control materials, serum and urine samples from pregnant women and newborns contained high concentrations of p55, and p55 was highly expressed by villous syncytiotrophoblasts. Thus, the present data suggest that shedding of specific receptors may contribute to the regulation of tumour necrosis factor activity throughout a normal pregnancy.

Cytokines↗
PubMed1992

Soluble TNF receptors in amniotic fluid and in urine from pregnant women.

Secretion of soluble cytokine receptors has been suggested as a mechanism for regulation of cytokine activity in vivo. The present investigation was performed to study whether secretion of soluble TNF (tumor necrosis factor) receptors (TNFRs) might be associated with pregnancy. There are two known molecular species of the TNFR, the 55-kDa TNFR and the 75-kDa TNFR. The 75-kDa, as well as the 55-kDa TNFR, was detected in urine from pregnant women, whereas only the 75-kDa TNFR was detected in urine from the non-pregnant group. The concentration of TNFRs in urine increased towards term and was reduced in association with spontaneous delivery. The soluble forms of both TNFRs were also detected in amniotic fluid. Collectively, the data suggest that secretion of soluble TNFRs during pregnancy might be a defence mechanism for the protection of the fetus against TNF action.

Amniotic Fluid↗