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A Ornoy

Publications and source records attributed to A Ornoy.

At least 73 records · Page 4Linked to original sources
PubMed1996

Teratogenic IgG from sera of women with spontaneous abortions seem to induce anomalies and yolk sac damage in rat embryos. A possible method to detect abortions of immunologic origin.

PROBLEM: Spontaneous abortions due to immunological rejection of the embryo may be avoided by immunotherapy with paternal allogeneic leukocytes but there is no appropriate method to detect and differentiate this group of aborters from other groups. METHODS: In previous studies we have demonstrated that in about two-thirds of sera from women with spontaneous abortions the IgG antibodies are responsible (alone or in combination with other factors) for the embryotoxic effects of these sera on cultured rat embryos. We presently cultured 10.5-day-old rat embryos on highly teratogenic serum ("high risk" serum that induced anomalies in more than 50% of the embryos) from women with spontaneous abortions, where the IgG fraction was exchanged with IgG from control sera and vice-versa. We studied by Transmission Electron Microscopy (TEM) the extent of yolk sac damage in comparison to the rate of embryonic anomalies. RESULTS: In cases where IgG antibodies were teratogenic, embryos cultured in control sera with IgG from "high risk" sera exhibited ultrastructural yolk sac damage as well as embryonic anomalies, and the yolk sacs cultured in "high risk" sera with control IgG were normal. In cases in which the IgG exchange did not change the rate of anomalies, as IgG was not teratogenic, yolk sacs from embryos cultured in "high risk" sera remained damaged, while yolk sacs from embryos cultured in control sera after IgG exchange stayed normal. Although no significant difference in total IgG levels was found between the groups, a higher IgG1 level in sera from women with teratogenic IgG was observed in comparison to control women's sera. The obstetrical history of the women with two or more abortions who took part in our study showed that there were more cases of unknown etiology of the abortion in the women from the "high risk" group. CONCLUSIONS: The serum and the IgG fraction from women with habitual abortions can be tested in whole embryo culture to evaluate the embryonic and yolk sac damage. On this basis it may be possible to detect the women in whom the habitual abortions result from immunological rejection.

Abortion, Habitual↗
PubMed1996

Outcome of children born to epileptic mothers treated with carbamazepine during pregnancy.

AIM: The purpose of the study was to assess whether there was an increased rate of congenital anomalies or significant developmental delay in infants of women with epilepsy who had been treated with carbamazepine during pregnancy. METHODS: 47 children were studied, aged 6 months-6 years, who were born to 37 epileptic mothers on carbamazepine monotherapy (group A). All children had a complete physical and neurodevelopmental assessment by a developmental paediatrician, and 41 a complete psychological evaluation. They were compared with 47 children of similar socioeconomic status (group B). RESULTS: Six of the 47 children in group A had typical facial features of 'carbamazepine syndrome'. The average cognitive score of children in group A was significantly lower than in group B. This was mainly because all six children with carbamazepine syndrome had a development quotient or intelligence quotient below 90. There were no differences between the two groups in physical growth or in the rate of major anomalies. Two children in group A had cleft palate but in each case this was found in a parent as well. CONCLUSIONS: In utero exposure to carbamazepine may result in 'carbamazepine syndrome' characterised by facial dysmorphic features and mild mental retardation. Prevalence of carbamazepine syndrome does not seem to be related to the dose of carbamazepine or the presence of maternal convulsions. It may depend upon heredofamilial factors that have yet to be defined. One possible factor is decreased activity of the enzyme epoxide hydrolase with resulting increased concentrations of carbamazepine epoxide which may be teratogenic.

Anticonvulsants↗
PubMed1996

The effects of in utero diagnostic X-irradiation on the development of preschool-age children.

High doses of X-irradiation may affect the developing human embryo and fetus, causing brain, eye, skeletal and other defects. Although the doses used in diagnostic irradiation are not considered to be high enough to cause fetal anomalies, it is unknown whether they affect the long-term development of the in utero exposed children. Using the Bayley or McCarthy developmental scales we examined 52 children born to mothers exposed to diagnostic X-irradiation of the abdomen and/or pelvis during the first trimester of pregnancy, 60 children born to mothers exposed during pregnancy (58 in the first trimester) to X-rays in areas other than the abdomen or pelvis, and 62 normal children without maternal exposure to X-rays during pregnancy. All children were aged 1-5 years at examination. Parental socioeconomic status was the same in all three groups. There were no differences in the results of the medical and neurological examination, and in the motor or congnitive scores among three groups. Embryonic or fetal exposure to X-irradiation in doses below 5 rads does not seem to have any effect on development during childhood.

Age Factors↗
PubMed1996

Role of reactive oxygen species in diabetes-induced embryotoxicity: studies on pre-implantation mouse embryos cultured in serum from diabetic pregnant women.

Sera from diabetic patients or sera with high levels of diabetic metabolic products, were found to affect mouse and rat blastocysts. In the present study we examined the earliest developmental stages at which human diabetic serum will be lethal to mouse pre-implantation embryos, and whether reactive oxygen species (ROS) are involved in these diabetes-induced injuries. We cultured 2-4 cell-stage embryos and blastocysts in a medium containing 30 or 50% serum obtained from pregnant women with diabetes Type I, Type II and gestational diabetes (GDM) for 72 h. The development of the 2-4 cell-stage embryos was delayed when cultured in 30% diabetic serum, but the viability was impaired to a lesser extent. Viability was reduced in blastocysts cultured in 50% diabetic serum, but the development of the living embryos was not delayed. Cyclic voltametry measures the oxidation potential of the tissue and the concentration of antioxidants, thus reflecting the total antioxidative activity of the embryos. Pre-implantation embryos cultured in diabetic serum had a lower concentration of antioxidants than embryos cultured in non-diabetic serum. It seems, therefore, that diabetic metabolic factors may induce embryotoxicity in pre-implantation embryos through derangement of the antioxidant defense mechanism. A similar mechanism is suggested for the diabetes-induced teratogenicity in post-implantation embryos.

Animals↗
PubMed1995

Anticalcification and antiresorption effects of bisacylphosphonates.

Some geminal bisphosphonates are used clinically in a number of important bone and calcium-related diseases. This work reports the anticalcification and antiresorption effects of a series of bisacylphosphonates, nongeminal compounds with varying chain lengths having oxo groups in alpha positions relative to the phosphonic functions. We compared the activity of the novel compounds to clinically used geminal bisphosphonates, and to a bisphosphonate devoid of the oxo groups. The interaction of the compounds with calcium was studied by various in vitro and in vivo models. We found that keto groups in alpha positions to the phosphonic functions render activity. The bisacylphosphonates with a shorter chain [(CH2)n, = 4, 6] were found significantly to inhibit hydroxyapatite formation and dissolution in vitro, the calcification of bioprosthetic tissue implanted subdermally in rats, and bone resorption in the intact young animal model. The various in vitro results were found to be in good correlation with the in vivo results. Structure-activity relationship studies indicate that both bisacylphosphonates and geminal bisphosphonates are active only when at least three ionizable groups are present in the molecule. The role of the keto groups is related to their contribution to chelating calcium and/or to their electron-withdrawing influence on acidity.

Acylation↗
PubMed1995

Effect of 17-beta-estradiol on the healing of tibial bone after marrow ablation.

The present study has been undertaken to demonstrate the effect of 17 beta-estradiol on the healing of tibial bones after marrow ablation. Ninety-six 4-month-old female rats were divided into three experimental groups: group 1 was subjected to ablation in both tibiae and to injection of vehicle; group 2 to ablation in both tibiae and estradiol administration, and group 3 to estradiol administration without ablation. Before the rats were killed, all on the same day, 8 animals of each group underwent treatment for 3, 6, 14 and 21 days, respectively: every second day, 0.1 ml arachis oil was injected intramuscularly into group 1 and 17 beta-estradiol into groups 2 and 3. An additional 8 untreated animals were used as controls. Tibial bones were studied chemically and morphologically. While the control and ablated animals gained weight, there was a significant decrease in the gain in body weight of estradiol-treated rats. Bone and ash weight were increased in all experimental groups. The ratios (%) of tibial ash weight and of tibial Ca and Mg contents to body weight significantly increased in all experimental groups, compared to the controls; whereas P increased only at 6 and 14 days. As shown by computerized histomorphometry, the height of the proximal tibial growth plate was increased following ablation, but not with estradiol treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Gender dependent effects of testosterone and 17 beta-estradiol on bone growth and modelling in young mice.

This study examined the effects of estrogen (17 beta-estradiol) and testosterone on the growth of long bones in male and female mice, with and without gonadectomy. Weight and nose-to-tail length were determined at 3 weeks of age at time of gonadectomy, 7 days later at the onset of hormone therapy, and throughout the treatment period. Gonadectomized mice exhibited an initial weight gain during the pretreatment period but length was unaffected. Hormone treatment altered weight gain in surgical and intact animals in a gender- and hormone-dependent manner. Estradiol enhanced weight gain in intact mice, but inhibited weight gain in ovariectomized mice. Lower doses of estradiol increased weight gain in orchiectomized mice at early time points. Testosterone increased weight in intact females and males, but not in gonadectomized mice. Estradiol increased nose-to-tail length in intact females at early time points, but inhibited length in ovariectomized females at later times, and it decreased length in intact males. Testosterone increased length in normal females and normal males. Serum Ca was unaffected by ovariectomy, but orchiectomy resulted in decreased levels. Estradiol reduced serum Ca in gonadectomized animals; serum Ca was increased by estradiol treatment in intact females. Changes in tibial bone weight, ash weight and mineral composition, and relative sizes of epiphyseal and metaphyseal bone were gender-, gonadectomy- and hormone-specific. Bone weight was greater in ovariectomized mice. Ash weight per bone was comparable, but there was an increase in Ca and P content with ovariectomy. Estradiol increased bone weight, ash content, and bone Ca and P in ovariectomized and intact females. Orchiectomy alone did not alter bone weight, ash content, or Ca and P, but orchiectomized mice were sensitive to estradiol; all parameters were increased in the orchiectomized animals treated with estradiol. Analysis of the ash content and Ca and P per mg bone, rather than per bone, demonstrated estradiol and testosterone alter net bone formation, but not the amount of mineral per unit bone. Ovariectomy increased hypertrophic cartilage. While estradiol did not alter tibial area in ovariectomized mice, it caused an increase in intact females. The total amount of growth plate cartilage in ovariectomized animals was decreased by estradiol to levels typical of intact animals due to a greater decrease in the hypertrophic cartilage in the ovariectomized mice, as well as a greater increase in metaphyseal bone area. Testosterone had no effect on these parameters in the females. Orchiectomy decreased the amount of growth plate cartilage, but increased the hypertrophic zone.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Gender-related effects of vitamin D metabolites on cartilage and bone.

Sex steroid hormones are known to have gender-dependent effects on bone and cartilage in vivo and in vitro. To investigate whether this is a general property of steroids, or is specific to the sex steroid hormones, we examined whether the effects on bone of 1,25-(OH)2D3 and 24,25(OH)2D3, the two active metabolites of vitamin D, are also gender-dependent. One-month-old male and female rats were treated for 1 month with various doses of 1,25-(OH)2D3, 24,25-(OH)2D3, or a combination of both metabolites. The direct effects of both metabolites on the skeleton of the treated animals were similar in male and female rats. 24,25-(OH)2D3 alone or in combination with 1,25-(OH)2D3 increased bone calcium and phosphorus, while 1,25-(OH)2D3 slightly decreased bone mineral content. 24,25-(OH)2D3 also enhanced the differentiation of cartilage in the growth plate, increasing the size of the hypertrophic zone. In addition, an increased metaphyseal bone volume was observed following 24,25-(OH)2D3 treatment in rats of both sexes, but not with 1,25-(OH)2D3. Vitamin D metabolites affected the weight gain of the experimental animals in a gender-dependent manner; 1,25-(OH)2D3 increased weight gain of male rats and 24,25-(OH)2D3 decreased weight gain of female rats. In addition, 1,25-(OH)2D3 increased bone weight and ash weight in male animals. These gender-dependent effects of vitamin D metabolites may occur indirectly via effects of sex steroid hormones, the latter being a sex-related effect.

24,25-Dihydroxyvitamin D 3↗
PubMed1994

The effects of sera from women with spontaneous abortions on the in vitro development of early somite stage rat embryos.

PROBLEM: Spontaneous abortions occur in 40 to 50% of pregnancies, but the causes for some abortions, especially those that are recurrent (spontaneous), are still unknown. METHOD: Following previous studies that demonstrated embryotoxic effects of sera from women with spontaneous abortions in preimplantation mouse embryos, we cultured 10.5-day-old rat embryos in sera from women after spontaneous abortions to look for specific teratogenic effects. RESULTS: About 50% of the embryos cultured in sera from women after spontaneous abortions were malformed, as compared to 19.1 and 27.1% malformations in embryos cultured in sera from women after a normal delivery and during a normal second trimester of pregnancy, respectively. We divided the sera from women who had spontaneous abortions into high-risk, and low-risk sera. In the high-risk sera from one abortion, we found 74.2% malformed embryos and in the high-risk group from two or more abortions this rate was 81.0%. This is compared to a rate of 17.1 and 10.3% in the low-risk sera, respectively. We have also found lower DNA and protein synthesis in the embryos cultured in high-risk sera compared to those cultured in low-risk and control sera. Transmission electron microscopy examination of yolk sacs cultured in high risk sera showed ultrastructural damage as represented by a lower number of microvilli and a higher number of inclusions in the entodermal cells when compared to controls. Amino acid chromatography of the serum and the concentrations of folic acid and zinc were similar in control and high-risk sera. CONCLUSION: It seems that the majority of sera from women with unexplained spontaneous abortions are teratogenic to rat embryos in culture. In about two-thirds of these sera the teratogenic factor(s) seem to be present in the IgG fraction.

Abortion, Habitual↗
PubMed1994

Gender-specific, maturation-dependent effects of testosterone on chondrocytes in culture.

This study examined the effects of testosterone on chondrocytes in vitro in order to determine whether the effects of testosterone were dependent on the stage of chondrocyte maturation and gender specific. Cells derived from male or female rat costochondral growth zone and resting zone cartilage were used as the cell culture model. [3H]Thymidine incorporation, cell number, alkaline phosphatase specific activity, and percent collagen production were used as indicators. Alkaline phosphatase specific activity in matrix vesicles and plasma membranes isolated from male and female chondrocyte cultures was measured to determine which membrane fraction was targeted by the hormone. The role of fetal bovine serum in the culture medium was also addressed. The results demonstrated that testosterone decreases cell number and [3H]thymidine incorporation in male chondrocytes, suggesting that it may promote differentiation of these cells. Alkaline phosphatase specific activity is stimulated in growth zone cells, with no effect on resting zone cells. The increase in enzyme activity is targeted to the matrix vesicles. Cells cultured in serum-free medium exhibit a dose-dependent inhibition of alkaline phosphatase activity when cultured with testosterone, even in the presence of phenol red. Testosterone-dependent stimulation of enzyme activity is seen only in the presence of serum, suggesting that serum factors are also necessary. Testosterone increased the percent collagen production in male cells only, regardless of the cartilage zone of origin. The results of this study indicate that the effects of testosterone are dependent on the time of exposure, presence of serum, and sex and stage of maturation of the chondrocytes. Testosterone-dependent stimulation of alkaline phosphatase specific activity is targeted to matrix vesicles.

Alkaline Phosphatase↗
PubMed1994

Evidence for receptors specific for 17 beta-estradiol and testosterone in chondrocyte cultures.

Recently, sex hormones were shown to stimulate chondrocyte differentiation and matrix protein synthesis in vitro in a sex-specific and maturation-dependent manner. The aim of the present study was to determine whether cytosolic receptors in these cells would specifically bind 17 beta-estradiol and testosterone, and if so, whether binding was gender- and maturation-dependent. Confluent, fourth passage cultures of cells derived from male or female rat costochondral growth zone and resting zone cartilage were homogenized and specific binding of 17 beta-estradiol or testosterone measured in the cytosolic fraction. Scatchard analysis indicated the presence of a high-affinity 17 beta-estradiol receptor (Kd = 4.5 to 8.7 x 10(-11) M), with low binding capacity (3.9 to 11.2 fmol/mg protein). Chondrocytes from female rats were found to have a significantly greater binding capacity for 17 beta-estradiol than chondrocytes from male rats. However, cells from both sexes had binding capacities that were independent of cell maturation. A high-affinity testosterone receptor (Kd = 4.3 to 6.3 x 10(-11) M) with low binding capacity (4.1 to 5.9 fmol/mg protein) was found in both males and females, but no difference in binding capacity was noted, either as a function of gender or stage of cell maturation. Immunohistochemistry using antibodies against 17 beta-estradiol and testosterone and the 17 beta-estradiol nuclear receptor (D-75) confirmed that 17 beta-estradiol and testosterone receptors were present in chondrocytes from both male and female rats. These data demonstrate that chondrocytes from growth zone and resting zone cartilage are capable of binding both 17 beta-estradiol and testosterone. This suggests that these hormones mediate their direct effects on chondrocytes via receptors specific for their appropriate ligand. The sex-specific effects of 17 beta-estradiol may be due to differences in receptor number between chondrocytes derived from female and male rats. In contrast, the sex-specific effects of testosterone may be regulated at the post receptor level since no differences in binding capacity were found between males and females.

Animals↗
PubMed1993

[First trimester sonographic diagnosis of acrania].

Anencephaly, a well-known lethal fetal malformation, was long considered to result from primary nonclosure of the neural tube. In the past few years other pathogenic mechanisms, such as reopening or degeneration of a closed neural tube have been suggested. High-resolution transvaginal ultrasonography, which provides fine visualization of the different stages in embryogenesis, allowed us to detect fetal acrania as early as the 12th week of gestation. Very high levels of alpha-fetoprotein, almost undetectable levels of unconjugated estriol (E3), and postabortion histology were consistent with anencephaly, suggesting that anencephaly is the end result of fetal acrania.

Adult↗
PubMed1993

Sex-dependent effects of 17-beta-estradiol on chondrocyte differentiation in culture.

This study examined the effects of 17-beta-estradiol (E2) on chondrocyte differentiation in vitro. Cells derived from male or female rat costochondral growth zone and resting zone cartilage were used to determine whether the effects of E2 were dependent on the stage of chondrocyte maturation and whether they were sex-specific. [3H]-Thymidine incorporation, cell number, alkaline phosphatase specific activity, and percent collagen production were used as indicators of differentiation. Alkaline phosphatase specific activity in matrix vesicles and plasma membranes isolated from female chondrocyte cultures was measured to determine which membrane fraction was targeted by the hormone. Specificity of the E2 effects was assessed using 17-alpha-estradiol. The role of fetal bovine serum and phenol red in the culture medium was also addressed. The results demonstrated that E2 decreases cell number and [3H]-thymidine incorporation in female chondrocytes, indicating that it promotes differentiation of these cells. Alkaline phosphatase specific activity is stimulated in both growth zone and resting zone cells, but the effect is greater in the less mature resting zone chondrocytes. The increase in enzyme activity is targeted to the matrix vesicles in both cell types, but the fold increase is greater in the growth zone cells. In male chondrocytes, there was a decrease in [3H]-thymidine incorporation at high E2 concentrations in resting zone cells at the earliest time point examined (12 hours) and a slight stimulation in alkaline phosphatase activity in growth zone cells at 24 hours. Cells cultured in serum-free medium exhibited a dose-dependent inhibition in alkaline phosphatase activity when cultured with E2, even in the presence of phenol red. E2-dependent stimulation of enzyme activity is seen only in the presence of serum, suggesting that serum factors are also necessary. E2 increased percent collagen production in female cells only; the magnitude of the effect was greatest in the resting zone chondrocyte cultures. The results of this study indicate that the effects of E2 are dependent on time of exposure, presence of serum, and the sex and state of maturation of the chondrocytes. E2-dependent stimulation of alkaline phosphatase specific activity is targeted to matrix vesicles.

Alkaline Phosphatase↗
PubMed1993

Localization of estrogen receptors in long bones and vertebrae of human fetuses.

In order to investigate the possible role of estrogen in the development of cartilage and bone we studied by immunofluorescence immunohistochemistry and autoradiography 26 human embryos and fetuses 7-22 weeks in gestational age associated with pregnancy interrupted for non-medical reasons. In order to demonstrate the presence of estrogen receptors (ERs) in human fetal cartilage, cryostat sections of long bones and lumbar and thoracic vertebrae were prepared for (1) fluorescent immunocytochemistry using an antiidiotypic monoclonal antibody to anti-estradiol receptor monoclonal Ab labeled with fluorescein isothiocyanate (FITC), (2) immunohistochemistry using monoclonal antihuman estradiol receptor antibody, labeled with strept. A-B immunoperoxidase, and (3) autoradiographic localization of estradiol using labeled (3H) 17 beta estradiol. In fetuses aged 10 weeks or older, intranuclear and perinuclear localization of ER was demonstrated by all methods, mainly amongst chondrocytes of the proliferating and higher hypertrophic zones of the epiphyses and in the cartilage of vertebral bodies. These data suggest that estrogen acts directly on chondrocytes of human fetuses through an ER-mediated mechanism.

Antibodies, Monoclonal↗
PubMed1993

Specific beta estradiol binding in cartilage and serum from young mice and rats is age dependent.

Various studies have shown a direct effect of beta estradiol on cartilage and bone. Such effects point to the possibility that specific receptors to estradiol exist in the growth plate cartilage as well as in bone. 3H-estradiol specific binding (EB) was therefore investigated in the supernatant of cartilage homogenates from the epiphyses and ribs of young growing mice and rats. High levels of EB were observed in the cytosol fraction of cartilage homogenates in the late fetal stage and in young rats and mice. The EB levels decreased gradually from late fetal stage up to 14 days of age in both groups of animals independent of their sex. Nuclear binding of 3H estradiol was also demonstrated by autoradiography in the chondrocytes of proliferating and hypertrophic zones. Estradiol binding was inhibited by high doses of unlabelled beta-estradiol, but not by alpha estradiol. Binding was also inhibited by tamoxifen and DES but not by testosterone. High levels of estradiol binding (EBS) were also observed in serum from young animals, but not in animals 2 months of age or older. Study of estradiol binding in cartilage and in serum of rats of the same age showed a significant difference in estradiol binding between these two systems. The difference in estradiol binding between serum and cartilage was seen in the response to inhibitors, Scatchard analysis, and temperature dependence. The results of our study imply that there are specific receptors for 17 beta estradiol in growth plate cartilage; they originate from chondrocytes, and their amount decreases with age. The effects of estradiol on endochondral bone growth seems therefore to be receptor mediated.

Aging↗