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Biomedical subjects

R A Pedersen

Publications and source records attributed to R A Pedersen.

At least 91 records · Page 5Linked to original sources
PubMed1982

Turnover of embryonic messenger RNA in preimplantation mouse embryos.

We have estimated the average half-life of embryonic messenger RNA in mouse embryos at two stages of preimplantation development. Embryos were collected at 48 and 75 h post-hCG and cultured overnight in the presence of [3H]uridine. Beginning at 65--68 h (morulae) or 92--94 h (early blastocysts), the label was withdrawn and replaced with unlabelled uridine, and samples were taken at intervals thereafter for RNA isolation. Label in cytoplasmic, poly(A)-containing RNA was measured after binding to oligo(dT)-cellulose, and was normalized to label in 28S and 18S ribosomal RNA, separated on sucrose gradients. The stability of rRNA in both stages was verified directly, as was the integrity and purity of the isolated mRNA. With morulae, the mRNA decay curve was monophasic, with an average half-life of 9.5 +/- 0.9 h. In three experiments with early blastocysts the decay curve appeared to be biphasic, consisting of short-lived (less than 6 h) and long-lived (30--50 h) components; in two other experiments a short-lived component was not evident. In all cases, however, the overall average half-life of mRNA in early blastocysts, determined by linear regression assuming monophasic kinetics, was greater than that in morulae. Our data indicate that the stability of embryonic mRNA increases by at least twofold during the morula-to-blastocyst transition. The results are considered in terms of the transcriptional dependency of early mouse embryos and the regulation of maternal and embryonic mRNA.

Animals↗
PubMed1981

Repair of the ultraviolet-irradiated male genome in fertilized mouse eggs.

Unscheduled DNA synthesis occurred in both male and female pronuclei of the mouse zygote in response to irradiation with ultraviolet light, indicating a capacity for excision repair. Furthermore, damage to DNA of the male gamete before fertilization can be repaired after the sperm enters the egg cytoplasm.

Animals↗
PubMed1981

Carotid-cavernous sinus fistula after external ethmoid-sphenoid surgery. Clinical course and management.

The occurrence of a carotid-cavernous sinus fistula following transethmoidal-sphenoid sinus surgery is unusual. The etiology of this complication is related to the variations in anatomic position of the carotid artery and in the thickness of bone overlying the artery in the lateral sinus wall. In the case reported herein, the clinical course was complicated by the development of cranial nerve palsies and ocular ischemia. The patient's symptoms worsened following an attempted to close the fistula with a microcatheter balloon and isobutyl-cyanoacrylate embolization. Dramatic improvement in the patient's condition was obtained by subsequent occlusion of the carotid artery on the side of the fistula with a microcatheter balloon.

Arteriovenous Fistula↗
PubMed1981

Inhibition of mouse blastocyst attachment and outgrowth by protease inhibitors.

Effects of protease inhibitors on development of mouse blastocysts and fibrinolytic activity of trophoblast were examined by growing embryos on monolayers of decidual cells in the presence of inhibitors. Nitrophenol-p-guanidino benzoate (NPGB) was the most effective inhibitor; 10(-4) M NPGB inhibited attachment and trophoblast outgrowth by 24% and 66%, respectively, and inhibited the fibrinolytic activity of trophoblast by 86%. The effects of NPGB were reversible, as demonstrated by the embryos' ability to attach and resume normal development when transferred to NPGB-free medium. Soybean trypsin inhibitor and epsilon-aminocaproic acid were less effective than NPGB in inhibiting blastocyst development. When 10(-4) M NPGB and 350 microgram/ml of soybean trypsin inhibitor were added together, blastocyst development and fibrinolytic activity were inhibited more severely than when either inhibitor was added alone. We suggest that at least two types of proteolytic activities in mouse blastocysts are involved in implantation, attachment requiring trypsin-like activity, and trophoblast outgrowth requiring both plasminogen activator and trypsin-like activity.

Animals↗
PubMed1980

Role of the blastocoele microenvironment in early mouse embryo differentiation.

During preimplantation development, the mouse embryo differentiates into an outer layer of cells, the trophectoderm, and an inner group, the inner cell mass. Tarkowski and Wróblewska proposed that this differentiation depends on the position of blastomeres in the morula, with outside cells giving rise to trophectoderm and inside cells producing the inner cell mass. This epigenetic hypothesis has been confirmed by other studies in which blastomere position was altered at the 4-cell of 8-cell stage, thus demonstrating the totipotency of the blastomeres at these stages. It was recently found that the inner cell mass of the early blastocyst is also totipotent and can form trophectoderm when isolated by immunosurgery. Because inner cells apparently become committed during the time that they are exposed to the distinct microenvironment of the blastocyst, we postulated that diffusible components or other factors in the blastocoele may have a role in the commitment of cells in the inner cell mass. We report here results, obtained by injecting donor cells into host blastocysts, showing that totipotent cells exposed only to blastocoele fluid differentiate into morphologically normal blastocysts, whereas those in contact with the blastocyst's inner surface do not.

Animals↗
PubMed1980

Radiation- and drug-induced DNA repair in mammalian oocytes and embryos.

A review of studies showing ultraviolet- or drug-induced unscheduled DNA synthesis in mammalian oocytes and embryos suggests that the female gamete has an excision repair capacity from the earliest stages of oocyte growth. The oocyte's demonstrable excision repair capacity decreases at the time of meiotic maturation for unknown reasons, but the fully mature oocyte maintains a repair capacity, in contrast to the mature sperm, and contributes this to the zygote. Early embryo cells maintain relatively constant levels of excision repair until late fetal stages, when they lose their capacity for excision repair. These apparent changes in excision repair capacity do not have a simple relationship to known differences in radiation sensitivity of germ cells and embryos.

Animals↗
PubMed1980

Cultured mouse embryos metabolize benzo[a]pyrene during early gestation: genetic differences detectable by sister chromatid exchange.

Mouse embryos explanted at 7 1/2 or 8 1/2 days of gestation were cultured in medium containing benzo[a]pyrene and supplemented with 5-bromodeoxyuridine to allow detection of sister chromatid exchanges. The murine Ah locus regulates the inducible metabolism of polycyclic hydrocarbons such as benzo[a]pyrene. A high frequency of sister chromatid exchange was induced by benzo[a]pyrene in embryos from three Ah-"responsive" inbred strains (BALB/cDub, C3H/AnfCum, and C57BL/6N); there was little or no increase in two Ah-"nonresponsive" inbred strains (AKR/J and DBA/2J). Benzo[a]pyrene also induced sister chromatid exchanges in the Ah-responsive recombinant inbred line B6NXAKN-12 but not in the Ah-nonresponsive recombinant inbred line B6NXAKN-3. Sister chromatid exchange in cultured Ah-responsive mouse embryos was thus shown to be a sensitive assay. These data provide direct evidence that genetically responsive mouse embryos (early postimplantation stage) possess the subcellular processes necessary for induction of enzymes that metabolize benzo[a]pyrene to its chemically active forms(s). Both the Ah regulatory gene product (a cytoslic receptor) and the structural gene product (inducible cytochrome P1-450) therefore appear to be functional at an early embryonic age. Furthermore, this metabolic capacity may play an important role in the damage to embryonic cells by polycyclic hydracarbons.

Animals↗
PubMed1980

Intermittent downbeat nystagmus and oscillopsia reversed by suboccipital craniectomy.

We describe an unusual case of vertical oscillopsia and primary position downbeat nystagmus associated with an adult Arnold-Chiari malformation. A unique aspect of the ocular motor abnormality was the intermittent nature of the nystagmus, which displayed no relationship to head position, emotion, or the Valsalva maneuver. Conventional computed tomography with posterior fossa views was normal, but metrizamide cisternography demonstrated an extramedullary mass originally believed to be a meningioma. There was a dramatic diminution of the visual complaints and downbeat nystagmus after suboccipital craniectomy for an Arnold-Chiari malformation. Nystagmus characteristics were documented by serial quantitative eye movement recordings.

Adult↗
PubMed1980

The free surface of mouse trophoblast in culture is non-adhesive for other cells.

Dispersed cells from cultured mouse cell lines, mouse macrophages, and inert microspheres were layered onto outgrowing mouse trophoblast in culture. The cells that settled onto the trophoblast remained round, in contrast to the elongated spreading shape they assumed on the glass substratum. The cells were readily dislodged from the trophoblast surface, whereas the microspheres were strongly adherent to trophoblast within 30 min. Scanning electron microscopy showed that trophoblast engulfed the spheres, but not the cells. Despite the lack of adhesion between cells and trophoblast, cell processes connected the two. The inability of cells to adhere to the free surface of the trophoblast could explain the trophoblast's ability to induce contact inhibition in co-cultured cells.

Animals↗
PubMed1979

Detecting mutations expressed during early development of cultured mammalian embryos.

Mammalian embryo culture systems can be used to study dominant lethal, recessive lethal, and visible mutations that are expressed between fertilization and early stages of organogenesis. The incidence of dominant lethal mutations has been determined for cultured mouse embryos by morphological observations during pre-implantation and early post-implantation growth in vitro, and the mechanisms of dominant lethal mutations have been studied cytogenetically. Recessive lethal mutations have been studied with cultured embryos, although they can be initially detected only with appropriate breeding protocols. Visible mutations that are due to deletions or single-site base alterations in the DNA can be detected in embryos by isoelectric focusing and gel-electrophoresis techniques.--The principal advantage of cultured embryos for detecting mutations and studying the mechanism of action of particular mutagens is that embryos are accessible for analysis before death with a minimum of indirect maternal effects. The primary disadvantages, which may be alleviated with improved culture conditions, are that only a limited amount of tissue is available, attrition and retardation occur, and offspring are not recovered for further breeding studies.

Animals↗
PubMed1978

Dose-response relationship for X-ray induced dominant lethal mutations detected in mouse embryos in vitro.

X-Irradiated male mice sired offspring that expressed dominant lethal mutations during development in vitro. These mutations were expressed as arrest of the embryo either before or after blastocyst formation and were induced in germ cells irradiated as spermatids. When the dose-response data for the induced dominant lethal mutation rate were fit to a linear-quadratic model for dose-response curves, they were found to be compatible with mutation induction by both one-track and two-track processes, and the calculated interaction distance agreed well with those values found for radiation-induced translocations in Vicia faba and mouse spermatogonia. This correlation suggests that dominant lethal mutations in embryos and translocations in germ cells both result from similar radiation-induced chromosome damage.

Animals↗