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Biomedical subjects

T Ranta

Publications and source records attributed to T Ranta.

At least 19 recordsLinked to original sources
PubMed1998

Doppler assessment of the maternal interlobar renal and uterine arteries in mid-pregnancy in women at low and high risk for pregnancy-induced hypertension.

PURPOSE: The purpose of this study was to examine the relationship between vascular resistance of the maternal intrarenal arteries and the main uterine arteries in pregnant women at low and high risk for pregnancy-induced hypertension. METHODS: The resistance indices (RIs) in the main uterine arteries and the interlobar branches of the right renal artery were measured by duplex Doppler sonography in 338 pregnant women at 21-24 weeks of gestation, including 175 women at high risk for pregnancy-induced hypertension. Of those, 54 patients had repeat Doppler measurements during pregnancy. RESULTS: Cross-sectional data showed no correlation between the RIs in the right interlobar renal arteries and either uterine artery. Furthermore, no relationship existed between persistent diastolic notching in the uterine arteries and the RI in the renal circulation. The mean renal artery RI was 0.62. Compared to that in patients with a normal outcome, the renal artery RI was not significantly different in patients who developed proteinuric pregnancy-induced hypertension (PPIH) or severe pregnancy-induced hypertension (PIH) later during pregnancy. Multiple analysis of variance for longitudinal data showed no correlation between the RI in the maternal renal arteries and gestational age, severe PIH, or PPIH. CONCLUSIONS: The RIs in the maternal intrarenal arteries and the main uterine arteries are not related to each other in pregnant women, even in patients with abnormal uterine artery Doppler findings, severe PIH, or PPIH.

Arteries↗
PubMed1997

Doppler assessment of the uterine and uteroplacental circulation in the second trimester in pregnancies at high risk for pre-eclampsia and/or intrauterine growth retardation: comparison and correlation between different Doppler parameters.

During a 20-month period we studied 175 pregnant women at high risk for hypertensive disorders of pregnancy or intrauterine growth retardation, and 172 patients at low risk, in a prospectively designed cross-sectional trial. Using duplex pulsed wave Doppler ultrasound, we recorded blood velocity waveforms from both main uterine arteries, the uteroplacental arteries in the region of placental implantation and the umbilical artery at 21-24 weeks of gestation. Persistent notches in the main stem uterine arteries and elevated resistance indices of > 0.68 in the uterine arteries and > 0.38 in the uteroplacental arteries were defined as abnormal waveforms. The incidence of proteinuric pregnancy-induced hypertension (PPIH) and intrauterine growth retardation (IUGR) were recorded as main outcome measures. Doppler proved to be more efficient at predicting a complicated pregnancy in those patients who were at high risk: a positive medical history alone was associated with a three-fold greater risk of developing PPIH and/or IUGR. In the high-risk group a single pathological Doppler sign accounted for an additional three- to four-fold increased risk, and the combination of all three pathological signs, a seven-fold additional risk for later disease. In this group PPIH and/or IUGR was found in 58.3%, compared to 8.3% if Doppler results were normal. The criterion for the definition of pathological Doppler results, whether persistent notching, the resistance index (RI) of the main stem uterine artery, or the RI in the arteries of the uteroplacental bed, was of minor importance, as all Doppler parameters were strongly correlated. However, the combination of all parameters was superior to a single parameter, and a bilateral notch was superior to a unilateral notch in terms of minimizing false-positive results. However, Doppler was less powerful in the population at low risk. Here PPIH and/or IUGR was seen in 6.1-6.4% in the group with abnormal Doppler findings compared to 5.2% in pregnancies with normal findings. None of the patients showed bilateral notching. In conclusion, pathological Doppler velocimetry of the uterine and uteroplacental circulation was a powerful predictor of PPIH and/or IUGR in high-risk pregnancies, identifying a group in which 58.3% would suffer from disease later in pregnancy. A combination of several Doppler parameters was superior to a single parameter, although the parameters were strongly correlated with each other.

Blood Flow Velocity↗
PubMed1995

Oral contraceptive containing natural estradiol for premenopausal women.

An open multicenter trial was performed in six centers in Finland to study the efficacy, safety and acceptability of a new biphasic oral contraceptive pill containing natural estradiol and cyproterone acetate. The participants were 288 women with a mean age of 39.3 +/- 3.4 years (range 30-49) who were willing to use the new pill as their only contraceptive method. In total, 23% of the women were smokers. The cumulative experience was 2800 treatment cycles during the first year. The net 12-month continuation rate was 63%. One pregnancy occurred in a woman who lost 5 tablets in the second treatment cycle, which gives a 12-month cumulative pregnancy rate of 0.4%. Serum progesterone values, determined twice during the third treatment cycle, showed ovulation inhibition in 95% of women. There were no serious side effects. Intermenstrual bleeding was recorded by 35.5% and 24.5% of women at 3 and 12 months, respectively. The bleedings became scantier in most women and dysmenorrhoea disappeared. No changes were observed in total and high density lipoprotein cholesterol concentrations after 1 year. With the exception of intermenstrual spotting, the efficacy, safety and acceptability of the new pill was almost as good as that of the modern low dose oral contraceptives. This is the first pill containing natural estradiol that has gained clinical acceptance and which can also be prescribed for smokers over 35 years old until the climacteric.

Adult↗
PubMed1995

Doppler flow velocimetry of the umbilical artery, uteroplacental arteries and fetal middle cerebral artery in prolonged pregnancy.

A total of 153 pregnant women, of at least 287 days' menstrual age, were studied in a prospectively designed cross-sectional trial. In addition to the non-stress test, contraction stress test, sonographic estimate of amniotic fluid and grade of placental maturation, Doppler measurements of the resistance index (RI) were taken in the umbilical artery, the uteroplacental arteries in the region of placental implantation and the fetal middle cerebral artery. Data were analyzed with regard to asphyxia and otherwise complicated fetal outcome. Furthermore, a possible relationship between grade of placental maturation, Doppler flow velocity waveforms and fetal outcome was investigated. Doppler resistance indices in the umbilical artery, uteroplacental arteries in the region of placental implantation and fetal middle cerebral artery did not change significantly with increasing gestation from 41 to 43 weeks. The grade of placental maturation on ultrasound examination was not related to fetal outcome or Doppler indices in the first two vessels. In all vessels examined in this study, the majority of Doppler measurements in pregnancies with subsequent asphyxia or otherwise complicated fetal outcome were within the 95% prediction interval for patients with normal fetal outcome. None of the patients showed absent diastolic flow in the umbilical artery. With the use of a cut-off value of RI = 0.62 in the umbilical artery, asphyxia could be predicted with 37% sensitivity and 75% specificity. Oligohydramnios and antpartum cardiotocography predicted asphyxia with 16% and 8% sensitivity and 95% and 96% specificity, respectively. Sensitivity for prediction of otherwise complicated fetal outcome by umbilical artery Doppler was only 7%.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Flow Velocity↗
PubMed1991

Testosterone-secreting virilizing adrenal adenoma with human chorionic gonadotrophin receptors and 21-hydroxylase deficiency.

A 60-year-old woman was evaluated for persistently elevated serum testosterone concentrations after bilateral ovariectomy. Her serum cortisol, androstenedione, dehydroepiandrosterone sulphate and 17-hydroxyprogesterone levels were normal, and decreased after dexamethasone administration. Those of testosterone (17.8-18.4 nmol/l) were remarkably high (normal range 0.7-2.8 nmol/l), were not suppressed by dexamethasone, but clearly increased after hCG administration (up to 128 nmol/l). Computed tomography revealed an adenoma in the right adrenal gland and adrenal scintigraphy under dexamethasone suppression visualized this adenoma. A right adrenalectomy was performed. (1) The tumour was histologically and ultrastructurally adrenocortical adenoma of zona reticularis cell type. (2) The adenoma tissue contained hCG receptors (198 fmol/g). (3) During tissue culture both ACTH and hCG were capable of maintaining its testosterone production, which was attenuated with time without stimulation. (4) The adenoma tissue did not elaborate 21-hydroxylated steroids in contrast to normal adrenal tissue. Thus the aberrant endocrine behaviour of this gonadotrophin-responsive testosterone-secreting adenoma of adrenal zona reticularis cell origin can be explained by ectopic functional hCG receptors and the lack of 21-hydroxylase activity.

Adenoma↗
PubMed1991

Doppler umbilical artery velocimetry in pregnancies complicated by intrahepatic cholestasis.

Doppler umbilical velocimetry is a useful clinical tool for antepartum fetal surveillance of pregnancies at risk of fetal compromise. Intrahepatic cholestasis of pregnancy is associated with an increased incidence of fetal death, which might due to the toxic effect of elevated maternal serum concentrations of bile acids. To study a possible effect of the concentration of bile acids on the umbilical circulation we performed pulse-wave Doppler velocimetry of the umbilical artery in 15 patients with intrahepatic cholestasis between 34 and 38 weeks of gestation. The findings were compared to the Doppler flow velocities of the umbilical artery of 129 normal pregnancies. Peak-systolic (A) and end-diastolic (B) velocities of two to three cardiac cycles were measured by electronic calipers and the Pourcelot (PR)-index (PR = (A - B)(A)) was calculated. Two of 29 Doppler measurements in patients with intrahepatic cholestasis were above two standard deviations (2 SD) of the values in normal pregnancies. No significant correlation was found between Doppler flow velocities and serum levels of bile acids (r = 0.20) or the levels of alanine aminotransferase (ALAT) (r = -0.05). The mean level of bile acids was 24 mumol/l with a maximum of 98 mumol/l. The mean level of ALAT was 165 IU/l with a maximum of 576 IU/l. Since even high levels of bile acids do not influence umbilical circulation, Doppler investigations of the umbilical artery seem to be of little value in studying the disease-specific risk of fetal compromise in pregnancies complicated by intrahepatic cholestasis.

Alanine Transaminase↗
PubMed1991

Discordant levels of serum bioactive LH in man as measured in different in-vitro bioassay systems using rat and mouse interstitial cells and human granulosa-luteal cells.

Serum samples from healthy men (n = 6), perimenopausal women (n = 9) and patients with polycystic ovarian disease (n = 4) were analysed for LH bioactivity by the two widely used in-vitro bioassay systems: the mouse and rat interstitial cell testosterone-formation assays. The results were compared with an assay employing LH-stimulated cyclic AMP production by cultured human granulosa-luteal cells. Average bioactive LH levels in the mouse cell assay were 1.6-fold higher than those measured using the rat assay. A good correlation (r = 0.89, P less than 0.01) was observed between the bioactive LH levels measured by these two assays. No significant difference was found between the sensitivities of the two assays: 0.009 +/- 0.003 IU/l (mean +/- S.E.M., n = 10) with rat cells and 0.011 +/- 0.003 IU/l (n = 10) with mouse cells. The LH level resulting in half-maximal stimulation of testosterone production in the mouse model was twofold higher than that in the rat model (0.185 +/- 0.020 vs 0.083 +/- 0.022 IU/l, P less than 0.01). The bioactive LH levels measured by the human granulosa-luteal cell assay averaged 12% higher than those obtained with the rat assay (r = 0.84, P less than 0.01), but 58% lower than levels measured with the mouse assay (r = 0.86, P less than 0.01). The data indicate that the target cell model used in the in-vitro bioassay of LH contributes to the documented discrepancies in reports on serum levels of bioactive LH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Human granulosa cells synthesize low molecular weight insulin-like growth factor-binding protein.

Human follicular fluid contains insulin-like growth factor I (IGF-I) and its low molecular weight binding protein (IGF-BP). We studied the synthesis of IGF-BP by the granulosa cells obtained after ovarian hyperstimulation for in vitro fertilization. The granulosa cells were cultured for 72 hours in Ham's F-10 medium supplemented with 10% fetal calf serum (FCS). Samples of the culture medium were collected every 24 hours. The IGF-BP concentration in culture medium increased from 1.2 to 2.1 micrograms/l at 48 h and to 3.3 micrograms/l at 72 h. De novo synthesis of IGF-BP was shown by incorporation of labeled methionine into immunoreactive IGF-BP, as detected by SDS polyacrylamide electrophoresis (PAGE) and fluorography. Our results demonstrate synthesis of IGF-BP in the human ovary.

Cells, Cultured↗
PubMed1989

Regulation of insulin-like growth factor-binding protein-1 production in human granulosa-luteal cells.

Human follicular fluid contains the insulin-like growth factor-binding protein (IGFBP-1) synthesized by ovarian granulosa cells. We studied the regulation of IGFBP-1 production by the granulosa-luteal cells from the hyperstimulated follicles of patients attending an in vitro fertilization program. The cells were first allowed to attach and recover from the hyperstimulation for 2 days. Then, a protein kinase-C activator, 12-O-tetradecanoyl phorbol-13-acetate (TPA), and adenylate cyclase activators, gonadotropins, FSH, hCG, cholera toxin, or prostaglandin E2 (PGE2) were added to the cells. The gonadotropins failed to increase IGFBP-1 production, whereas it was enhanced by TPA and to a lesser extent by cholera toxin and PGE2. The maximal response to TPA occurred at the concentration of 1.0 ng/mL, and the enhancing effect of TPA was detected at 24 h. PGE2 stimulated IGFBP-1 production; the lowest effective concentration was 10(-8) mol/L. The mean highest response was 4.3-fold and occurred at the PGE2 concentration of 10(-5) mol/L. The effect of PGE2 on IGFBP-1 production became detectable at 24 h, and it continued to increase up to 72 h. PGE2 also increased granulosa-luteal cell progesterone production in a dose- and time-dependent manner. Incorporation of [35S]methionine into immunoreactive IGFBP-1, as detected by sodium dodecyl sulfate-polyacrylamide electrophoresis and fluorography, was also increased by TPA. This suggests that TPA accelerated the synthesis of IGFBP-1. Our results indicate that the production of IGFBP-1 by human granulosa-luteal cells can be regulated both via protein kinase-C- and adenylate cyclase-dependent pathways.

Cells, Cultured↗
PubMed1989

Efficacy of gonadotropin-releasing hormone agonist (buserelin) in the treatment of endometriosis.

In a multicenter study, the efficacy of and tolerance of 6 months' intranasal gonadotropin-releasing hormone agonist (buserelin) treatment (300 micrograms x 3/day) on laparoscopically verified endometriosis was evaluated in 25 patients. At second-look laparoscopy at the end of medication, the mean endometriosis score had fallen by 82.2%. All endometriosis-associated symptoms and physical findings decreased or almost disappeared during buserelin administration. After discontinuing therapy, they showed a tendency to reappear, but nevertheless they were milder after one year of follow-up, than before treatment. Seven (54%) of the 13 women wishing pregnancy actually conceived. Vaginal irregular spotting bleedings during the first 2 months occurred in 7 patients. No patient withdrew from the trial because of side effects, although almost all women developed symptoms of estrogen deficiency (serum estradiol concentrations fell to menopausal levels).

Administration, Intranasal↗
PubMed1988

Differential regulation of hCG and progesterone secretion by cholera toxin and phorbol ester in human cytotrophoblasts.

The secretion of hCG and progesterone (P) by human cytotrophoblasts was studied in response to cholera toxin (CT), which activates adenylate cyclase, and 12-O-tetradecanoylphorbol-13-acetate (TPA), a protein kinase C stimulator. During a 24 h incubation CT and TPA increased hCG and P secretion in a concentration-dependent manner. At maximal effective concentrations, CT (1.0 ng/ml), TPA (10 ng/ml) and CT plus TPA stimulated hCG production by 5.7-, 2.7- and 10.0-fold, respectively, and P production by 1.8-, 1.8- and 2.0-fold, respectively. Time-course studies indicated that these effects became detectable after 12 h and increased up to 48 h of incubation. During a 24 h culture TPA potentiated CT-induced cAMP formation by 1.4-fold indicating that its effects on hCG production may be, at least partly, mediated through cAMP. In conclusion, CT and TPA are potent stimulators of human cytotrophoblast hCG and P production. Simultaneous stimulation by these agents results in potentiation of hCG production whereas P production remains at the same level as with CT or TPA alone. The results suggest that the endocrine activity of human cytotrophoblasts is under multihormonal control and hCG and P secretion are differentially regulated.

Cells, Cultured↗
PubMed1988

Regulation of the production of placental protein 5 by human endometrial stromal cells; the role of prostaglandins E2 and F2 alpha.

Cultured human endometrial stromal cells were found to release placental protein 5 (PP5), a glycoprotein with properties of a serine protease inhibitor. Progesterone had no effect on PP5 release, but cholera toxin and 12-O-tetradecanoylphorbol 13-acetate stimulated PP5 release in a time- and concentration-dependent fashion. Prostaglandin E2 (PGE2) caused a parallel increase in cAMP and PP5 release in a time- and concentration-dependent fashion. The lowest PGE2 concentration which increased cAMP and PP5 release was 1 X 10(-9) M. Maximal increase in cAMP (42-fold) and PP5 (25-fold) release was obtained by 10(-5) M PGE2. Stimulation of cAMP by PGE2 was detectable at 15 min and was followed by an increased PP5 release at 24 h. The concentrations of prostaglandin F2 alpha (PGF2 alpha) which stimulated cAMP and PP5 release were pharmacological suggesting that this effect is nonspecific. The results indicate that the activation of cAMP- and protein kinase C-dependent pathways in endometrial stromal cells increases the production of PP5. PGE2 could be one of the physiological ligands employing the cAMP-dependent pathway in endometrial stromal cells.

Cells, Cultured↗
PubMed1988

Biological and immunological activity of human chorionic gonadotrophin in maternal serum during early pregnancy.

Serum chorionic gonadotrophin (hCG) levels were measured by three different assay methods in 20 women admitted to legal abortion and 21 patients having insulin-dependent diabetes, both during 8 to 14 weeks of pregnancy. Biological activity of hCG was determined with a mouse Leydig cell in-vitro bioassay, binding activity of the hormone to LH receptors by rat testis radioreceptorassay, and immunoreactivity by fluorimmunoassay. Bioassay and radioreceptorassay gave 1.4 and 1.7-fold higher hCG concentrations than fluoroimmunoassay using the same standard. Correlations between hCG levels measured by bioassay and fluoroimmunoassay (r = 0.81; P less than 0.01) and radioreceptorassay and fluoroimmunoassay (r = 0.95; P less than 0.01) were good. The results emphasize the heterogeneity of hCG in the pregnancy serum. Different domains of the molecules are recognized by assay methods based on antigenicity, receptor binding and biopotency of the hormone.

Adult↗
PubMed1988

Characterization of functional type I insulin-like growth factor receptors from human choriocarcinoma cells.

Specific receptors for insulin-like growth factor I (IGF-I) on cultured human choriocarcinoma cells (JEG-3 and BeWo) were characterized. The binding of 125I-labeled recombinant (Thr59)IGF-I to the cells was reversible and time, temperature, and pH dependent. Steady state of binding occurred after 16 h at 4 C, pH 7.4. Natural human IGF-I (hIGF-I), hIGF-II, recombinant (N-Met)IGF-I, rat multiplication-stimulating activity, and insulin were 200%, 37%, 37%, 1.6%, and 0.1% as potent as (Thr59)IGF-I in inhibiting the binding of [125I]iodo-(Thr59)IGF-I to JEG-3 cells, respectively. Epidermal growth factor was ineffective. The half-maximal displacement of [125I]iodo-(Thr59)IGF-I by unlabeled (Thr59)IGF-I occurred at 11 +/- 2 ng/ml (mean +/- SEM) in both JEG-3 and BeWo cells. Scatchard analysis of the competitive binding data revealed linear plots indicating a single species of binding sites with an association constant of 0.8 X 10(9) M-1 for the binding of [125I]iodo-(Thr59)IGF-I to both cell lines. The binding capacity was 30,000 and 20,000 sites/cell for JEG-3 and BeWo cells, respectively. Chemical cross-linking of [125I]iodo-(Thr59)IGF-I to JEG-3 cells revealed two receptor complexes of 130K and 260K. Their formation was completely inhibited by an excess of unlabeled (Thr59)IGF-I or hIGF-II. Increasing amounts of insulin affected both labeled bands equally, suggesting that the 130K and 260K bands represent the monomer and dimer forms, respectively, of the ligand-binding alpha-subunit of type I IGF receptor. (Thr59)IGF-I, in a dose-dependent manner, stimulated uptake of nonmetabolizable alpha-[3H]aminoisobutyric acid by JEG-3 cells, showing that the receptor is biologically active. Our results demonstrate that choriocarcinoma cells possess functional high affinity type I IGF receptors and suggest that IGF-I is involved in the growth-regulating processes of JEG-3 and BeWo cells. These cells may provide a useful model to study the role of IGFs in trophoblast physiology.

Aminoisobutyric Acids↗
PubMed1988

Insulin-like growth factor (IGF) binding protein from human decidua inhibits the binding and biological action of IGF-I in cultured choriocarcinoma cells.

The placenta expresses genes for insulin-like growth factors (IGFs) and possesses IGF-receptors, suggesting that placental growth is regulated by IGFs in an autocrine manner. We have previously shown that human decidua, but not placenta, synthesizes and secretes a 34 K IGF-binding protein (34 K IGF-BP) called placental protein 12. We now used human choriocarcinoma JEG-3 cell monolayer cultures and recombinant (Thr59)IGF-I as a model to study whether the decidual 34 K IGF-BP is able to modulate the receptor binding and biological activity of IGFs in trophoblasts. JEG-3 cells, which possess type I IGF receptors, were unable to produce IGF-BPs. Purified 34 K IGF-BP specifically bound [125I]iodo-(Thr59)IGF-I. Multiplication-stimulating activity had 2.5% the potency of (Thr59)IGF-I, and insulin had no effect on the binding of [125I] iodo-(Thr59)IGF-I. 34 K IGF-BP inhibited the binding of [125I] iodo-(Thr59)IGF-I to JEG-3 monolayers in a concentration-dependent manner by forming with the tracer a soluble complex that could not bind to the cell surface as demonstrated by competitive binding and cross-linking experiments. After incubating the cell monolayers with [125I]iodo-(Thr59)IGF-I in the presence of purified binding protein, followed by cross-linking, no affinity labeled bands were seen on autoradiography. In contrast, an intensely labeled band at 40 K was detected when the incubation medium was analyzed, suggesting that (Thr59)IGF-I and 34 K IGF-BP formed a complex in a 1:1 molar ratio. Also, 34 K IGF-BP inhibited both basal and IGF-I-stimulated uptake of alpha-[3H]aminoisobutyric acid in JEG-3 cells. RNA analysis revealed that IGF-II is expressed in JEG-3 cells. We conclude that decidual 34 K IGF-BP inhibits the cellular binding and biological action of IGFs in JEG-3 cells. Our data show that JEG-3 cells represent a cell type that can produce IGF, but not IGF-BPs. These cells may thus provide a useful model system for a better understanding of autocrine growth regulation mediated by the IGFs.

Binding, Competitive↗