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Biomedical subjects

F Naftolin

Publications and source records attributed to F Naftolin.

At least 253 records · Page 14Linked to original sources
PubMed1983

In vitro development of the mammalian embryo.

Normal growth and differentiation of mammalian embryos in vitro during the preimplantation period appear to be dependent upon the availability of appropriate metabolic substrates. For preimplantation embryos, defined conditions of culture have been achieved only in a few laboratory species. There is now evidence that differentiation factors isolated from fetal calf serum and human placental cord serum may promote further development of blastocysts. Postimplantation rat and mouse embryos can be cultured during the organogenesis period with rat or human sera in roller bottles. The embryonic differentiation of the rat at this stage of development is progressively retarded in such cultures with male rat serum. The embryonic development is not improved, even in sera obtained from rats at different days of gestation (12, 15-16, and 20-21). Inability to grow placental tissues simultaneously with embryos, accumulation of unfavorable substances, and rapid depletion of nutrients contribute to the retardation of embryonic growth. To improve growth and differentiation of conceptuses, a continuous culture system with the possibility of infusion of increasing concentrations of oxygen in the roller bottle gas atmosphere has been developed. This improved method allows considerable continuous growth and differentiation from the neurula stage with development of numerous primary organs. Utilizing these in vitro culture methods during pre- and postimplantation periods, it is now possible to assess embryotoxic or teratogenic potential of drugs and chemical agents. The postimplantation culture procedure allows a more precise assessment of mechanisms associated with anomalous embryonic differentiation. Bioactivation of teratogens and effects of active toxic metabolites on organ primordium differentiation have been shown by combining embryo culture with a hepatic microsomal activating system. Microinjection of teratogens and cells into conceptus compartments is being used to elucidate specific anomalous differentiation processes.

Animals↗
PubMed1983

Kinetics of catechol estrogen-estrogen receptor dissociation: a possible factor underlying differences in catechol estrogen biological activity.

The mechanisms underlying the differences in uterotrophic potency between 2- and 4-hydroxyestrogens were explored. Doses of estradiol (E2)(10 micrograms/kg), 2-OHE2 (500 micrograms/kg) and 4-OHE2 (100 micrograms/kg) sufficient to induce near maximal cell nuclear estrogen receptor (ERn) binding were injected subcutaneously into 26 day old female rats. Uterine ERn concentrations declined more rapidly after 2-OHE2 than after E2 or 4-OHE2. E2 and 4-OHE2 both elicited a significant increase in uterine wet weight, measured at 24-36 hrs after injection. 2-OHE2 had no significant effect and neither synergized with nor antagonized the effects of simultaneously administered E2 or 4-OHE2. Under in vitro conditions at 25 degrees C, 2-hydroxyestrone (2-OHE1) and 2-OHE2 both dissociated from the receptors more rapidly than either their parent monophenolic estrogens or the corresponding 4-hydroxyestrogens. These results suggest that differences in estrogenic potency between 2- and 4-hydroxyestrogens may partly be a function of the dissociation kinetics of their estrogen receptor complexes.

Animals↗
PubMed1983

Tamoxifen-induced increase in cytosol progestin receptor levels in a case of metastatic endometrial cancer.

A patient with endometrial carcinoma metastatic to the groin has had serial cytosol estrogen (ERc) and progestin (PRc) receptor determinations during hormonal therapy. The primary lesion was well differentiated and a left iliac node metastasis had high ERc and borderline PRc levels. PRc levels increased substantially in a subsequently appearing right groin metastasis at three times during the clinical course when the patient was treated with the antiestrogen tamoxifen. The patient had a partial response to the first course of tamoxifen and at one later time briefly had stabilized disease on tamoxifen plus medroxyprogesterone acetate. Tamoxifen with and without progestin should be further evaluated in the treatment of endometrial carcinoma.

Adenocarcinoma↗
PubMed1983

The relationship of circulating estradiol to tardive dyskinesia in men and postmenopausal women.

In order to assess the relationship between tardive dyskinesia (TD) and baseline circulating concentrations of estradiol, prolactin and homovanillic acid, we studied 43 outpatient men and postmenopausal women on chronic antipsychotic medication. Serum estradiol did not correlate with severity of TD, antipsychotic medication dose, serum prolactin or plasma HVA. Multiple regression analysis indicated a significant relationship between plasma HVA and severity of TD in postmenopausal women. These findings support the hypothesis that estrogen might serve a protective role against neuroleptic-induced striatal dopamine pathology.

Antipsychotic Agents↗
PubMed1983

Analysis of failure of microsurgical anastomosis after midsegment, non-coagulation tubal ligation.

Improved prognosis of tubal anastomosis after midsegment tubal ligation is an important goal. A review of the causes of failure in 124 patients operated on from 1974 through 1978 is presented. All patients were ovulatory and had normal results in postcoital tests and semen analyses. All tubal ligations had been non-coagulation. The overall pregnancy rate was 74.2%. The follow-up period was 18 months to 5 years. Of the 32 failures, 6 had bilaterally occluded tubes, 3 had severe ovulatory dysfunction, in 12 the husbands had not previously fathered a child, and 11 were unexplained. In 20.7% of successes and in 37.5% of failures the husband had not previously fathered a child. This significant difference suggests an undefined male factor.

Adult↗
PubMed1983

The use of high-dose human menopausal gonadotropin in an in vitro fertilization program.

Sixty-three normal ovulatory women suffering from obstructive tubal disease not corrected by previous surgery were enrolled in an in vitro fertilization (IVF) program. To achieve a large number of mature follicles, a relatively high dose of human menopausal gonadotropin (hMG) was administered (19 +/- 4 ampules/cycle). Monitoring consisted of daily follicular ultrasonography and serum estradiol measurements. Human chorionic gonadotropin (10,000 IU) was administered when more than two large follicles (1.6 to 1.8 cm in diameter) were visualized. Fifty-five laparoscopies for oocyte retrieval were performed. A mean of 4.3 follicles per woman were aspirated, and 3.2 oocytes per woman were recovered. The oocytes were preincubated for 8 or 24 hours according to the morphologic degree of mucification and dispersal of the oocyte-corona-cumulus complex. Seventy-seven percent of the oocytes were fertilized and were transferred into the uterus 38 to 40 hours after insemination. Fifty-two women received one to eight embryos (mean, 3.5 +/- 1.9), and 9 (17%) conceived. This regimen of high-dose hMG precludes the need for serum or urine luteinizing hormone monitoring, because the occurrence of spontaneous ovulation is low. It is valuable in increasing the number of fertilizable oocytes, the percentage of women undergoing embryo transfer, and compensates with multiple oocyte transfer for the high embryonic loss involved in IVF.

Adult↗
PubMed1983

HLA-DR antigen on human trophoblast.

To assess the presence of human leukocyte antigens (HLA) on first trimester human trophoblast cells, frozen sections of villous trophoblast and monolayer cultures of isolated cells from placental villi were prepared and exposed to a mouse monoclonal antibody directed against HLA-DR and then incubated with fluorescein-conjugated goat antimouse antibodies. Fluorescence microscopy demonstrated that HLA-DR antigens were present on only the small polygonal epithelioid cells of the monolayer culture. The crescentic staining pattern was consistent with widespread distribution of antigen on the cell membrane. There was no staining over giant multinucleated structures or on fibroblasts of such cell cultures. No HLA-DR was detected when this indirect immunofluorescent technique was applied to tissue sections of villous trophoblast. Existence of high concentrations of hCG in culture supernatants and coincident localization of both hCG and HLA-DR using antibodies conjugated with rhodamine or fluorescein on the polygonal epithelioid cells indicate the trophoblastic origin and expression of HLA-DR antigen under in vitro monolayer culture conditions.

Cells, Cultured↗
PubMed1983

Anovulation in female rats induced by neonatal administration of the catechol estrogens, 2-hydroxy-estradiol and 4-hydroxy-estradiol.

The effects of estradiol (E2) and its 2- and 4-hydroxylated metabolites on gonadotrophin regulation in the female rat brain were examined. Neonatal female rats were injected from day 1 through 5 with E2, 2-OHE2 and 4-OHE2, at doses of 0.1, 1 and 10 micrograms/day. At 2, 6 and 24 h after the last estrogen injection, some animals from each treatment group were killed and the concentration of estrogen receptors (ERn) in their brain cell nuclei determined. The remaining animals were allowed to mature. Their vaginal smear patterns were examined from 7 to 9 and from 15 to 17 weeks of age. They were then ovariectomized and tested for their capacity to exhibit a luteinizing hormone (LH) surge in response to estrogen and progesterone injections. In a parallel series of experiments, the affinities of the three test estrogens for alpha-fetoprotein (AFP) were determined from in vitro competition studies with fetal rat serum. All three estrogens increased brain cell nuclear ERn concentrations, measured at 2 h after the final injection. E2 was more potent in this respect than either 4-OHE2 or 2-OHE2. E2 and 4-OHE2 competed for binding to AFP to an approximately equal extent. 2-OHE2, however, was a much weaker competitor for AFP than either of the other two compounds. The neonatal E2 and 4-OHE2 treatments reduced the number of animals showing regular cyclic vaginal smears, at all three doses tested. In contrast, 2-OHE2 significantly affected vaginal cyclicity only at a dose of 10 micrograms/day.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

[Biochemical and morphological study of pregnant rat myometrium: role of steroid receptors and gap junction formation in onset of parturition].

In order to understand the mechanism involved in the onset of labor in rats, a series of biochemical and morphological studies were done on pregnant rat myometrium, during the latter half of pregnancy and in the postpartum period. It was observed that plasma progesterone (P) levels gradually declined between day 15 and 20 of pregnancy as did cytosol (PRC) and nuclear P receptors (PRN). In contrast, nuclear estrogen receptors (ERN), both occupied and unoccupied, increased in number during this period of time. Between 24 to 6 hrs prior to labor, plasma P levels and PRN reached a nadir (day 15 v.s. day 21; 776 +/- 88.5 and 187.4 +/- 40.4 fmol/mg DNA, mean +/- S.E., p less than 0.01), while ERN showed an abrupt increase (day 21 v.s. day 22; 1710.6 +/- 61.1 and 3254.8 +/- 203.8 fmol/mg DNA, p less than 0.01), and remained high during labor. After delivery, ERN gradually decreased, but PRN showed a surge between 6 to 12 hrs postpartum in concert with the rise in plasma P levels due to ovulation. Electromicroscopic quantitation of gap junctions (gis) also showed a sharp increase in the number of gjs during labor (day 21 v.s. during labor; 2.0 +/- 0.4 and 17.9 +/- 1.5 gjs per 1,000mcm of plasma membrane, p less than 0.01). A large number of gjs were observed during the first 12 hrs postpartum, but they abruptly disappeared thereafter. These observations suggest that in rats, prepartum accumulation of ERN may facilitate the formation of gjs, which serve as a means for either electrical or chemical excitations to synchronize myometrial contractions and initiate/sustain labor. After delivery, on the other hand, P seems to down-regulate the number of gjs and induce rapid myometrial quiescence during postpartum ovulation which allows the myometrium to be receptive to fertilized ovum.

Animals↗
PubMed1982

Salpingostomy for ectopic pregnancy in the sole patent oviduct: reproductive outcome.

The ultimate success of conservative surgery for tubal ectopic pregnancy is difficult to evaluate in the presence of a potentially normal contralateral fallopian tube. Fifteen cases of tubal pregnancy with only one functional fallopian tube were treated by linear salpingostomy at Yale-New Haven Hospital between 1975 and 1980. The overall term viable pregnancy rate to date is 53%; the recurrent ectopic pregnancy rate is 20%. Twenty-seven percent of those patients operated upon until now have not conceived. These statistics are based on a 100% follow-up of at least 1 year, with all patients trying actively to conceive. Review of the literature on conservative treatment of ectopic pregnancy when only one tube is present reveals an intrauterine pregnancy rate of 61% and a repeat ectopic pregnancy rate of 17%. We conclude that linear salpingostomy is an acceptable surgical technique for the treatment of tubal ectopic pregnancy, because this experiment, by its nature, eliminates the variable performance of the contralateral tube in relationship to subsequent intrauterine pregnancy and repeat ectopic pregnancy in these patients.

Fallopian Tubes↗
PubMed1982

Estrogen stimulation of 3-o-methyl-D-glucose uptake in isolated rat hepatocytes.

The effect of in vivo and in vitro estrogen treatment on 3-O-methyl-D-glucose (30MDG) uptake in isolated rat hepatocytes was examined. A 1-h preincubation of isolated hepatocytes with 17 beta-estradiol (E2) or 17 alpha-ethynyl estradiol stimulated uptake of 30MDG in a dose-dependent fashion. The response appeared to be sterospecific, in that 17 alpha-estradiol was approximately 100-fold less effective than its 17 beta isomer. By itself, the triarylethylene antiestrogen, nafoxidine, slightly increased hepatocyte 30MDG uptake, while in combination with estrogen, nafoxidine completely blocked the effects of both E2 and 17 alpha-ethynyl estradiol. The protein synthesis inhibitor, cycloheximide, inhibited basal 30MDG uptake and abolished the stimulatory effect of estrogen. Kinetic analysis indicated that the estrogen effect resulted from an increase in the Vmax of the 30MDG transport system, with no measurable change in its Km. In vivo estrogen treatment, using either estrogen injections or continuous release Silastic E2 capsules, produced an increase in hepatocyte 30MDG uptake of 52-86%. A similar (66%) increase was seen in pregnant animals between the 14th and 19th days of gestation. These findings demonstrate that estrogens exert a rapid stimulatory effect on hepatocyte hexose transport. This effect is qualitatively similar to the response to estrogen of the hexose transport systems in other estrogen target tissues, such as the uterus. In addition, the results provide further support for the concept that the effects of the triarylethylene antiestrogens are both tissue and end-point dependent. Although previous studies have shown that nafoxidine exerts estrogen-like effects on hepatic renin substrate production, the present data indicate that, with respect to hepatocyte 30MDG, nafoxidine is almost a pure estrogen antagonist.

3-O-Methylglucose↗
PubMed1982

Unfilled nuclear oestrogen receptors in the rat brain and pituitary gland.

This study describes the presence of a population of oestrogen receptors in cell nuclei from the pituitary gland and brain of untreated and oestradiol-treated ovariectomized rats. The receptors behaved as if they were not occupied by oestradiol. These 'unfilled' oestrogen receptors could be distinguished from occupied nuclear receptor sites on the basis of their ability to bind [3H]oestradiol at low temperatures (0-4 degrees C). Occupied receptors bound labelled [3H]oestradiol only under exchange conditions at an increased temperature (25 degrees C). Unfilled and occupied nuclear receptors were physicochemically similar in terms of sedimentation coefficients in sucrose density gradients containing 0.4 M-KCl (4-5S), equilibrium dissociation constants for reaction with [3H]oestradiol (0.2-0.6 nmol/l) and ligand specificity. In ovariectomized rats, unfilled receptors constituted more than 75% of the total nuclear receptor population. One hour after i.v. treatment with oestradiol (3.6 micrograms/kg), both total and unfilled nuclear receptor concentrations increased and then subsequently declined over the next 12 h. The increase in unfilled sites was, however, proportionately less than that occurring in the filled component; at 1 h after oestradiol injection unfilled sites constituted less than 20% of the receptors present in brain and pituitary cell nuclei. The physiological significance of unfilled nuclear oestrogen receptors remains unknown. The observations that they exist in various oestrogen target tissues and that their levels are influenced by oestradiol treatment suggest a possible role for these receptors in the mechanism of oestrogen action.

Adrenalectomy↗
PubMed1982

Comparative pharmacology of oestrogens and catechol oestrogens: actions on the immature rat uterus in vivo and in vitro.

The effects of primary and catechol oestrogens on the uterus of the immature rat were compared. Because differences between the in-vivo and in-vitro oestrogenic actions of catechol oestrogens on the secretion of LH had been observed, their effects on a peripheral target organ, the uterus, were examined under similar conditions. In-vivo effects were assessed by measurement of uterine weight, induction of uterine cytoplasmic progestogen receptors, and by histological examination. In-vitro actions were determined by measurement of oestrogen-specific induced protein. It was found that the uterotrophic effects in vivo of 4-hydroxyoestradiol were indistinguishable from those of oestradiol whereas 2-hydroxyoestradiol was only weakly oestrogenic and 2-hydroxyoestrone had no effect. However, in vitro, 2-hydroxyoestradiol was as effective as 4-hydroxyoestradiol or oestradiol in stimulating synthesis of uterine induced protein, and 2-hydroxyoestrone, although less potent than oestradiol, had a significant effect. These results were consistent with the observed effects on the secretion of LH. The differences between in-vivo and in-vitro uterotrophic properties of catechol oestrogens can be explained on the basis of known pharmacokinetic factors.

Animals↗
PubMed1982

Tamoxifen therapy for advanced ovarian cancer.

Thirteen patients with rapidly advancing recurrent epithelial ovarian cancers, in whom chemotherapy and, in some cases, radiation therapy failed, were treated with the estrogen antagonist tamoxifen. The presence of cytosol estrogen receptors, which have recently been identified in ovarian cancer specimens, was determined in the tumor from each patient prior to tamoxifen treatment. No complete responses were observed. One patient had a partial response and 4 patients had prolonged stabilization of disease. All patients with stabilized disease had estrogen receptor levels that were borderline or high. Eight patients demonstrated no response to oral tamoxifen therapy, but 5 of these had partial small bowel obstruction secondary to advanced recurrent cancer. As tamoxifen in this preliminary study may have stabilized rapidly advancing recurrent ovarian cancer in combination with cytotoxic chemotherapy should be considered.

Adult↗
PubMed1982

Aromatase in the central nervous system.

Central (central nervous system and pituitary) aromatization appears to be a fundamental process for endocrine control and development. Metabolism of androgens to estrogens and the subsequent metabolism of estrogens have been proven in many species, including humans, and linked to estrogen action. Thus, aromatization appears to initiate or to be involved in activities of importance to endocrine function at the central level and their effects peripherally. In the context of breast cancer, central aromatization relates to the control of gonadotrophins and other pituitary-brain hormones which may effect metabolism at the level of the breast. For example, follicle-stimulating hormone can increase aromatization and may be a factor in the control of such metabolism in breast tissue.

Androgens↗
PubMed1982

Early postnatal development of the arcuate nucleus in normal and sexually reversed male and female rats.

The ultrastructural characteristics of the arcuate nucleus in the rat were examined at days 2, 5, 10 and 15 postpartum in order to evaluate the cytological development of the nucleus during sexual differentiation of the hypothalamus. In an effort to accentuate potential steroid-dependent structural features, the nucleus in normal male and female rats was compared with that of rats in which sexual differentiation had been reversed, by subcutaneous injection of testosterone proprionate in neonatal female rats, and by bilateral castration of neonatal male rats. The arcuate nucleus did not reveal any evidence of sexual dimorphism nor any effects of neonatal castration or androgenisation. The nuclei of any animals exhibited an increase, with age, in morphologically mature neurons and synapses. At day 15, however, the nuclei still possessed features indicative of an immature neural system, including organelle-poor profiles of young neurons, growth cones, focal points of cellular degeneration, and a lack of myelinated axons and morphologically mature macroglial cells. Of particular interest was the observation that neonatally-castrated male rats failed to exhibit a quantitative increase in whorl bodies by day 15 post partum, in contrast to the characteristic increase in whorl bodies observed in male rats that were castrated in adulthood. The results indicate that the arcuate nucleus undergoes progressive structural maturation during sexual differentiation of the hypothalamus and that this development is not altered ultrastructurally by changes in the steroid environment. At day 15 postpartum, an age at which sexual differentiation is irreversibly fixed, the nucleus remains a partially developed neural system. Further structural maturation, both neuronal and glial, will undoubtedly contribute to changes in hypothalamic regulation of the pituitary-gonad axis which occur with age. The lack of whorl body proliferation in neonatally-castrated males indicates that the arcuate nucleus of developing animals does not respond morphologically to negative steroid feedback mechanisms in a manner comparable to that of adults. The proliferation of whorl bodies in response to steroid withdrawal is thus an age-dependent phenomenon.

Animals↗