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Biomedical subjects

S Yagel

Publications and source records attributed to S Yagel.

At least 109 records · Page 6Linked to original sources
PubMed1993

The regulatory role of tri-iodothyronine on the production of alpha-fetoprotein and albumin by mouse fetal liver cells.

The purpose of this study was to assess possible effects of tri-iodothyronine (T3) on the production of alpha fetoprotein (AFP) and albumin by mouse fetal liver cells. AFP from serum-free conditioned media of TIB73 mouse fetal liver cells was measured by immunoradiometric assay and albumin was measured by chromogenic assay. The expression of mRNAs was quantified by Northern blotting analysis. A marked inhibition of AFP secretion was found as well as an increase in albumin produced by T3 in a dose-dependent manner. The effects of T3 AFP and albumin secretion paralleled the effects of T3 on the steady-state expression of mRNAs encoding albumin and AFP. These data may point to a possible role of T3 in the transcriptional switch from AFP to albumin during fetal development and may explain the observation of high levels of AFP in cases of congenital hypothyroidism.

Albumins↗
PubMed1993

Trophoblasts protect the inner cell mass from macrophage destruction.

Several mechanisms have been suggested to account for the survival of the semiallogeneic fetus in the maternal uterus. However, no data are available to explain how the blastocyst resists the high number of macrophages in the uterus at the time of implantation. The present study examines the in vitro development of murine 3.5-day-old syngeneic or semiallogeneic blastocysts in the presence of nonactivated or lipopolysaccharide (LPS)-activated macrophages. It was found that the in vitro development of blastocysts was undisturbed by the presence of nonactivated or LPS-activated macrophages. The outgrowing trophoblasts were not only nonadhesive to the macrophages but also repelled them actively, thus preventing them from reaching the inner cell mass (ICM). Removing the zona pellucida by use of pronase or killing the ICM by irradiation did not alter the repulsion of macrophages by the trophoblasts. On the other hand, removal of the trophectoderm by antibody and complement treatment rendered the macrophages adhesive and destructive to the ICM. Four of 15 ICM (27%) were destroyed by nonactivated macrophages, and all of the ICM (15/15) were destroyed by LPS-activated macrophages. It is noteworthy that the addition of colchicine, cytochalasin B, proteinase inhibitors, anti-transforming growth factor-beta (TGF beta) antibodies, and indomethacin had no effect on the repulsion of macrophages by the trophoblasts. Therefore, it seems that microtubular proteins, microfilaments, extracellular matrix-degrading enzymes, TGF beta, and prostaglandins are not involved in the repulsion process. These results indicate that trophoblasts protect the ICM from the destructive action of macrophages by a repulsion mechanism of an as yet unknown nature.

Animals↗
PubMed1993

Cytokine-mediated regulation of rat ovarian function: interleukin-1 stimulates the accumulation of a 92-kilodalton gelatinase.

It is known that the mammalian ovary possesses a complete interleukin-1 (IL-1) system replete with ligands, receptors, and a receptor antagonist. To further assess the hypothesis that IL-1 may play an intermediary role in gonadotropin-triggered ovulation, we have set out to determine whether IL-1 is capable of promoting ovarian collagenase biosynthesis, an established component of the ovulatory cascade. Untreated cultured whole ovarian dispersates from immature (25 day old) rats constitutively elaborated several collagenolytic species as assessed in a gelatin matrix. A major 72 kilodalton (kDa) gelatinase (GL) was particularly apparent. Treatment with IL-1 beta produced selective dose- and cell density-dependent increments in the accumulation of a 92-kDa GL species. Administration of an IL-1 receptor antagonist neutralized the IL-1-induced stimulation of the 92-kDa GL in a dose-dependent fashion thereby supporting the presumption that the IL-1 effect is receptor mediated. Studies of comparable cellular densities of granulosa or enriched theca-interstitial cultures demonstrated the IL-1 induced 92-kDa GL to be highly expressed in the enriched theca-interstitial but not in the isolated granulosa cell preparations. Treatment with transforming growth factor-beta 1, a putative regulator of IL-1 action, significantly attenuated IL-1-induced 92-kDa GL accumulation thereby suggesting a potential regulatory paracrine/autocrine role for this agent in ovarian gelatinase economy. Initial characterization revealed the 92-kDa GL species to be a metalloproteinase present in its proenzyme zymogenic form. Taken together, our present findings reveal the ovarian expression of a constitutive 72-kDa GL and of an IL-1-stimulated 92-kDa GL the accumulation of which is particularly marked in enriched theca-interstitial preparations. These observations, along with the demonstration of the gonadotropin-dependent preovulatory induction of ovarian IL-1 gene expression, provide strong indirect support for the view that IL-1 may be the centerpiece of an intraovarian regulatory loop concerned with the promotion of the ovulatory cascade.

Animals↗
PubMed1993

Gonadotropin-mediated inhibition of proteolytic enzymes produced by human trophoblast in culture.

We investigated the effect of gonadotropins on protease that were suggested to be implicated in the invasive activity of the trophoblast. hCG levels ranging from 10 x 10(3) to 333 x 10(3) IU/L produced a dose-dependent inhibition of the in vitro globinolytic activity of the purified proteases trypsin, chymotrypsin, and urokinase, but failed to inhibit plasmin, collagenase, elastase, and tissue-type plasminogen activator. Likewise, FSH inhibited purified trypsin and urokinase, but not plasmin or tissue-type plasminogen activator. Culture medium conditioned with human trophoblast displayed serine protease and urokinase-like activities; exposure of the cultured trophoblast to exogenous hCG markedly suppressed serine protease and urokinase activities in the conditioned medium. A short treatment of the conditioned medium with trypsin abolished the hCG-mediated inhibition of urokinase activity. The present findings offer an explanation for earlier observations that hCG reduced collagenase activity in trophoblasts without affecting the level of collagenase-specific mRNA. The present results are also consistent with the concept that hCG, by its direct ability to inhibit certain serine proteases and urokinase in trophoblast, suppresses a protease-mediated conversion of procollagenase to active collagenase. The ability of hCG to prevent initiation of the collagenolytic cascade suggests that gonadotropins may regulate the transient invasive activity of the trophoblast.

Aprotinin↗
PubMed1993

High levels of human chorionic gonadotropin retard first trimester trophoblast invasion in vitro by decreasing urokinase plasminogen activator and collagenase activities.

Trophoblast cells of the blastocyst and of the first trimester placenta penetrate the endometrial basement membrane during the process of implantation and placental development. However, this invasive capacity seems to be restricted to the fetomaternal interface, as few trophoblast cells can be identified in the decidua, and trophoblasts rarely penetrate the maternal blood vessels. We have shown that the high invasive ability of first trimester human trophoblasts in vitro depends on collagenase activated by plasmin generation. In our study we used invasive first trimester trophoblast cells in conjunction with as in vitro amnion invasion assay to assess the role of hCG in the invasive process. hCG inhibited trophoblast invasion capacity in a dose-dependent fashion but exerted no effect on the ability of the trophoblasts to attach to the basement membrane. The activity of collagenase by trophoblasts (determined by zymography) was down-regulated by hCG, again in a dose-dependent manner. In contrast, hCG had no effect on production of the tissue inhibitor of metalloproteinases. Similar inhibitory effects of hCG on urokinase-plasminogen activator (uPA) and the activity of trophoblast-conditioned media were shown (measured by degradation of S-2444). The hCG effect on collagenase production was not mediated by the expression of procollagenase messenger RNA (mRNA), the expression of the mRNA encoding tissue inhibitor of metalloproteinase, or the expression of uPA mRNA, suggesting posttranscriptional control of hCG action. High levels of hCG attenuated the activity of commercial uPA but had no effect on commercial collagenase activity. These observations suggest that hCG may play a role in the trophoblast invasion process by inhibition of uPA activity, in turn decreasing collagenase activity and thereby reducing trophoblast cell invasion.

Cell Adhesion↗
PubMed1993

The prognosis of hypertensive disease of pregnancy accompanied by intrauterine growth retardation in relation to parity.

Twenty-two primiparous women with hypertensive disease of pregnancy (HDP) associated with intra uterine growth retardation (IUGR) were compared with 20 parous women in whom HDP associated with IUGR appeared for the first time in a second or a later pregnancy. Both groups of women were followed up for 10-13 years. The course of the disease among the parous women was more severe as compared to the primiparous women; the mean gestational age at the first increase in blood pressure and gestational age at delivery were significantly earlier in the parous group (33.3 weeks +/- 3.5 v.s. 35.3 +/- 3.2 weeks, p < 0.01, 36.2 weeks +/- 2.2 v.s. 37.6 +/- 1.9 p < 0.01 accordingly). Maternal indication for induction of labor because of uncontrollable hypertension was present in 77% of the cases in the parous group as compared to 31% in the primiparous group (p < 0.05). These complications were present in 66% of subsequent pregnancies in the parous group as compared with 31% in the primiparous group (p < 0.05). Chronic hypertension developed in 33% of the parous group as compared with 20% in the primiparous group. These differences show that the manifestation of HDP is more severe in women in whom HDP with IUGR occur for the first time in a second or a later pregnancy than in those in whom this complication occurs for the first time in a second or a later pregnancy than in those in whom this complication occurs for the first time in their first pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Intrauterine device failure: relation to its location within the uterine cavity.

OBJECTIVE: To investigate the possible role of position of the intrauterine device (IUD) in accidental pregnancies. METHODS: We examined the location of the IUD in 97 normal women 45-60 days post-insertion, and in 25 pregnant women with the device in situ. RESULTS: A cervically located IUD was identified in seven of 97 women (7.2%) after insertion and in 13 of 25 pregnant women (52%) with the device in situ. The odds ratio for a woman with an intracervical IUD to be pregnant compared with a woman with an IUD in the uterus was 13.93 (95% confidence limits 4.13-48.96). Sonographic follow-up of the pregnant women revealed no change in IUD location during early gestation. CONCLUSIONS: We suggest that cases of failed contraceptive action of the IUD may be secondary to a malpositioned device. A sonographic survey can identify displaced devices. Reinsertion of the IUD in such cases is recommended.

Adult↗
PubMed1992

Extended fetal echocardiographic examination for detecting cardiac malformations in low risk pregnancies.

OBJECTIVE: To improve the rate of prenatal detection of cardiac malformations in a low risk population. DESIGN: Comparison of extended fetal echocardiography with the standard four chamber view in detecting abnormalities. Extended echocardiography comprised the four chamber view and visualisation of the left ventricular outflow tract, the right ventricular outflow tract, and the main pulmonary artery and its branches. In cases with abnormal results complete echocardiographic studies were performed by a paediatric cardiologist using M mode, Doppler, and colour flow mapping techniques. SETTING: Obstetric ultrasonographic unit at Shaare-Zedek Medical Centre, Jerusalem. SUBJECTS: 5400 fetuses in low risk pregnancies between 18 and 24 weeks' gestation (mean 21 weeks); 53 were lost to follow up. MAIN OUTCOME MEASURES: Detection of abnormality before and after birth. RESULTS: During the study 23 infants (0.4%) were born with cardiac abnormalities, 21 of whom had major structural and functional heart disease. 18 fetuses had heart disease diagnosed prenatally, 11 by the four chamber view alone (sensitivity 48%) and a further seven by extended echocardiography (sensitivity 78%). Five fetal cardiac defects were missed prenatally (false negative rate 22%). These included coarctation of aorta, persistent truncus arteriosus, tetralogy of Fallot, ventricular septal defect, and pulmonic stenosis. Only one false positive diagnosis (coarctation of aorta) was made (specificity 99.9%, false positive rate 0.1%). The abnormality was correctly identified in 17 out of 18 cases. CONCLUSIONS: The extended fetal heart examination detected 86% (18/21) of major abnormalities in a low risk population. The examination should be incorporated into routine prenatal ultrasonographic investigations.

Adolescent↗
PubMed1992

The effect of ethinyl estradiol on endometrial thickness and uterine volume during ovulation induction by clomiphene citrate.

OBJECTIVE: To assess the deleterious effect of clomiphene citrate (CC) on the development of the endometrium and its improvement by the addition of ethinyl estradiol (E2). PARTICIPATING PATIENTS: Infertility-treated patients, monitored for induction of ovulation or timing of insemination (control group). DESIGN: We studied four groups of women during an ovulatory cycle with various treatment schedules. Group 1: untreated patients; group 2: patients treated by CC; group 3: patients treated by CC + ethinyl E2; group 4: patients treated by human menopausal gonadotropin. Follow-up of the patients was done by vaginal ultrasonography and measurements of blood E2. RESULTS: In the group treated by CC, both endometrial thickness and uterine volume growth during the follicular phase were lower as compared with untreated controls and menotropin-treated patients. The addition of ethinyl E2 to these patients reversed this deleterious effect of CC without interfering with ovulation. CONCLUSION: Ethinyl E2 may reverse the deleterious effect of CC on endometrial development during the follicular phase.

Adult↗
PubMed1992

Fetal middle cerebral artery blood flow during normal active labour and in labour with variable decelerations.

OBJECTIVE: To assess the distribution of fetal blood flow impedance of the umbilical and middle cerebral artery in active uncomplicated labour and in labour complicated by variable decelerations. INTERVENTIONS: Blood flow impedance of the umbilical and fetal middle cerebral arteries was assessed by means of pulsed Doppler ultrasonography and measured by the resistance index (RI) and the systolic/diastolic ratio. SUBJECTS: 35 women at 38-40 weeks gestation admitted to, or monitored in the intrapartum unit. One group of 25 women had a normal active labour, the second group of 10 women were in active labour with moderate variable decelerations. A control group of 25 women--healthy pregnant women at term but not in active labour. All three groups were comparable for maternal age and parity. SETTING: Hospital department of obstetrics and gynaecology, Israel. DESIGN: A prospective descriptive study. RESULTS: There was a 40% reduction in middle cerebral artery blood flow impedance in the two groups of women in active labour compared with the control group. Umbilical blood flow did not differ significantly between the three groups. Fetal middle cerebral blood flow impedance in labour was not significantly different in uncomplicated labours and those complicated by fetal heart rate decelerations. CONCLUSIONS: During active labour, mechanisms that may be unrelated to low fetal blood oxygen content reduce fetal brain blood vessel impedance.

Blood Flow Velocity↗
PubMed1992

The role of abnormal fetal heart rate in scheduling chorionic villus sampling.

OBJECTIVE: To assess the value of fetal heart rate (FHR) measurements in predicting spontaneous fetal loss in pregnancies scheduled for chorionic villus sampling (CVS). DESIGN: A prospective descriptive study. SETTING: Two hospital departments of obstetrics and gynaecology in Israel. SUBJECTS: 114 women between 9 and 11 weeks gestation scheduled for chorionic villus sampling (CVS). INTERVENTIONS: Fetal heart rate was measured by transvaginal Doppler ultrasound and compared with a monogram established from 75 fetuses. Whenever a normal FHR was recorded, CVS was performed immediately. RESULTS: 106 women had a normal FHR and underwent CVS; two of these pregnancies ended in miscarriage. In five pregnancies no fetal heart beats could be identified and fetal death was diagnosed. In three pregnancies an abnormal FHR was recorded and CVS was postponed; all three pregnancies ended in miscarriage within 2 weeks. CONCLUSION: Determination of FHR correlated with crown-rump length could be useful in predicting spontaneous miscarriage before performing any invasive procedure late in the first trimester.

Adult↗
PubMed1992

Extraluminal hyperechogenic echo detected by transvaginal ultrasonography as a prognostic factor in recurrent hydatidiform mole.

Measuring beta hCG titers by either bioassay or radioimmunoassay has become the cornerstone in the management and treatment of hydatidiform mole. It is this very determination which will indicate either spontaneous remission or the need for chemotherapy treatment due to rising or plateauing titers. Herein, we report on the potential assistance of a unique ultrasonographic appearance of a hyperechogenic shadow located in the uterine wall, before and after an attempt for full evacuation of hydatidiform mole. The behavior of this echogenic area was more sensitive in predicting the course of the disease than did the beta hCG titers. Thus, using transvaginal sonography may serve as another predictor and indicator in evaluating the treatment of hydatidiform mole.

Adult↗
PubMed1992

Rupture of ectopic pregnancy following disappearance of serum beta subunit of hCG.

The introduction of sensitive assays for the beta subunit of hCG (beta-hCG) and improved ultrasound technology for diagnosis and monitoring of ectopic pregnancy have changed the clinical approach to the management of ectopic pregnancy. Only a few reports have been published of patients with ectopic gestation and negative serum beta-hCG levels. None of these described rupture of ectopic pregnancy following the decline of beta-hCG levels to below 10 mIU/mL. We describe a case of ectopic pregnancy, managed expectantly, in which rupture and hemoperitoneum occurred after the decline of beta-hCG levels to below 10 mIU/mL.

Adult↗
PubMed1992

Oncogenic consequences of down-modulating TIMP expression in 3T3 cells with antisense RNA.

We have used recombinant DNA technology to engineer a set of murine 3T3 cell lines that vary in the extent to which they express TIMP, tissue inhibitor of metalloproteinases, and we have found that both invasiveness and tumorigenic potential are conferred when TIMP production is impaired. These cell clones were produced by transfecting immortal Swiss 3T3 cells with plasmid constructs capable of expressing antisense TIMP RNA under the control of the mouse metallothionein promoter (Khokha & Denhardt, AntiCancer Res. 7: 653-660, 1987). The ability of these cells to invade the amnion membrane in vitro was dependent upon metalloproteinase expression (Yagel et al., JNCI 81: 768-775, 1989). Cells expressing TIMP at a reduced level acquired the ability to form tumors in nude mice (Khokha et al. SCIENCE 243: 947-950, 1989). These results suggest not only that TIMP controls the invasive character of the immortal 3T3 cell, but also that it determines cellular tumorigenic potential in the mouse. We presume that these phenotypes are conferred as a consequence of a net increase in extracellular matrix metalloproteinase activity resulting from the reduced quantities of TIMP secreted. The lag in formation of tumors by the cells down-modulated for TIMP production suggests that further changes in gene expression may be necessary. In support of this hypothesis, recent experiments indicate that the expression of genes encoding one or more matrix metalloproteinases is increased in cell lines derived from tumors that have developed from the engineered cells. Thus, in the immortal 3T3 cell line, TIMP has the properties of a tumor-suppressor gene, or anti-oncogene.

3T3 Cells↗