bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insulin but not progesterone promotes the biosynthesis of glycogen in Xenopus laevis oocytes: Implications on the control of glycogen synthase by phosphorylation, dephosphorylation
Authors: Debauche Pascal , Baras Benoǐt , Devos Pierre 
Published: June 2005

AbstractInsulin, the well‐known hypoglycemic hormone, mimics progesterone in promoting the resumption of meiosis within the oocyte of Xenopus laevis. Both hormones exert their action through the inhibition of protein kinases and the activation of protein phosphatases. Because glycogen synthase is an enzyme regulated by a kinases/phosphatases cascade, we investigated the effect of insulin and progesterone on the regulation of glycogen synthesis and glycogen synthase throughout the oogenesis of Xenopus laevis oocytes. In this framework the maximal activity of synthase “a” is concomitant with the vitellogenic period characterized by a drastic increase in the amount of glycogen. Oocyte glycogen synthase is inhibited by cAMP‐dependent phosphorylation and stimulated by 20 mM Mg2+. The magnesium effect is inhibited by μmolar concentrations of okadaic acid and suggests that oocyte glycogen synthase is activated by dephosphorylation achieved by protein phosphatase‐1. The okadaic acid effect is itself thwarted by the specific inhibitor of protein kinase A, confirming the role of this kinase in the regulation of glycogen synthase. Finally, working on intact ripe oocytes, we showed that insulin but not progesterone increases glycogen synthesis and glycogen synthase “a” activity and lowers the rates of phosphorylation, especially in the glycogen‐bound proteins. © Wiley‐Liss, Inc.
Ovarian follicles of rainbow trout (Oncorhynchus mykiss) cultured within lamellae survive well, and sequester and process vitellogenin
Authors: Nagler J. J. , Tyler C. R. , Sumpter J. P. 
Published: June 2005

AbstractThe culture of ovarian follicles of fish has proved difficult and this has hindered research on factors controlling oocyte growth. Here we describe a system for the in vitro culture of vitellogenic ovarian follicles from rainbow trout (Oncorhynchus mykiss) contained within their lamellae, and compare it to results obtained with individual follicles. Gross morphological appearance, volume change, rate of vitellogenin (VTG) uptake, and subsequent processing of VTG were used as indicators of viability and physiological status. In culture, follicles maintained within ovarian lamellae had significantly higher survival rates compared to individual follicles divested of connective tissue and surface epithelia (90% vs. 45% survival, respectively) after 6 d. Although surrounded by follicle cell layers and surface epithelia, oocytes within lamellae still sequestered VTG, albeit at a lower rate than individual follicles devoid of their surface epithelia. Further, VTG sequestered by follicles within lamellae was processed into lower molecular weight proteins within the oocyte. The superior survival rate of ovarian follicles within lamellae (compared to those divested of their surface epithelia), together with their ability to incorporate VTG and process it suggest that this method provides an excellent system for studying factors controlling oocyte growth. © Wiley‐Liss, Inc.
Role of glutamate and GABA in the pathophysiology of epilepsy
Authors: Holmes Gregory L. 
Published: June 2005

AbstractEpilepsy, a paroxysmal disorder characterized by abnormal neuronal discharges, is common in children. While the causes of epilepsy are many, the fundamental disorder is secondary to abnormal synchronous discharges of a network of neurons. Whether or not a seizure occurs in a child depends upon the balance between excitability and inhibition. Central nervous system neurotransmitters have significant effects on neuronal excitability and play a pivotal role in brain excitability. The most common excitatory neurotransmitter in the brain, glutamate, has been implicated in both the initiation and propagation of seizures as well as brain damage that can occur following prolonged or repeated seizures. Gammaaminobutyric acid, the most common inhibitory neurotransmitter, usually suppresses seizure activity, although in absence seizure drugs that enhance GABA may exacerbate seizures. Experience with GABA indicates that certain neurotransmitters may have either anticonvulsant or proconvulsant effects depending on the neuronal networks involved. While other neurotransmitters also have effects on neuronal excitability, their function in epilepsy remains to be defined. © 1995 Wiley‐Liss, Inc.
Empiric recurrence risks in common and uncommon congenital heart lesions
Authors: Nora James J. , McGill Charles W. , McNamara Dan G. 
Published: June 2005

AbstractEmpiric recurrence risks in sibs for the eight most common and four uncommon congenital heart lesions have been obtained from a study of 1405 patients with congenital cardiovascular malformations. Risks to offspring of parents with any of four common congenital heart diseases were determined in a study of 210 adults who had congenital heart defects and who had reproduced. The recurrence risks are presented and are found to approximate the prediction of the multifactorial inheritance hypothesis.
Influence of 2‐deoxy‐D‐glucose and sodium fluoroacetate on respiratory metabolism of rat embryos during organogenesis
Authors: Spielmann Horst , Meyer‐Wendecker Rainer , Spielmann Frauke 
Published: June 2005

AbstractThe effect of various concentrations of 2‐deoxy‐D‐glucose (2DG) and sodium fluoroacetate (SFA) on the Q of day‐11 and 12 rat embryos was studied in vitro. The dose‐response curves—% inhibition versus log concentration—were linear for 2DG between 500 μM and 50 mM; day‐11 rat embryos showed a higher rate of inhibition than day‐12 embryos and adult kidney tissue. The inhibitory effect of SFA on the embryonic Q in vitro was significantly lower than on adult kidney tissue slices. These in vitro effects are in agreement with recent investigations on the energy metabolism of rat embryos that revealed a change from glycolysis to an oxidative, respiratory metabolism during organogenesis. The administration of a single dose of 2DG and SFA to pregnant rats at day 9 or 10 of pregnancy significantly reduced the Q and dry weight of the embryos at day 11, whereas both parameters were unchanged at day 12. The same treatment was nonteratogenic, which is in contrast to the findings of other investigators.
Glucocorticoid inhibition of RNA synthesis and the critical period for cleft palate induction in inbred mice
Authors: Andrew Floyd D. , Bowen Donna , Zimmerman Ernest F. 
Published: June 2005

AbstractA comparison was made of the teratogenic effects of triamcinolone (induction of cleft palate) and its ability to inhibit RNA synthesis in the C3H and A/J strains of mice. The “critical period” for induction of cleft palate in C3H mice was at day 11.5 of gestation, 3 days before palate shelf elevation. The extent of inhibition of RNA synthesis decreased when the drug was administered at later times of development and was correlated with a lower concentration of drug in fetuses. However when a higher dose (15 mg/kg) was administered at a later time (day 13.5), although the fetal drug concentration and inhibition of RNA synthesis were approximately equal to that produced by 10 mg/kg triamcinolone administered at day 11.5 (which produces 80% cleft palate), the frequency of cleft palate was much lower (33%). Thus the critical period for teratogenesis is not related to maximal absorption of drug. In A/J mice the critical period was at day 12.5. When one‐fifth as much triamcinolone (2 mg/kg) was administered to A/J mice the inhibition of RNA synthesis in palate and total fetus was similar to that seen after 10 mg/kg in the C3H strain. The concentration of drug in fetuses of each strain was approximately proportional to the dose administered. Thus A/J may be more sensitive to the effect of triamcinolone on RNA synthesis than C3H. The mechanism of action of the glucocorticoid with respect to the “critical period,” inhibition of RNA synthesis, and strain differences is discussed.
Evaluation of the teratogenic potential of a spray adhesive in hamsters
Authors: Murphy James C. , Collins Thomas F. X. , Black Thomas N. , Osterberg Robert E. 
Published: June 2005

AbstractPregnant Syrian hamsters were placed in a 100‐1 static inhalation chamber for 30 min twice daily on days 5‐10 of gestation and exposed to 8.0 ± 0.13, 11.6 ± 0.11, or 13.23 ± 0.49 g of “Foil Art Adhesive” and killed on day 14. Controls were placed in adjacent identical chambers but received no spray. The spray adhesive was toxic but not teratogenic at the doses administered. Maternal alopecia occurred upon exposure to the 2 highest dose levels, and 1 female died during exposure to the highest dose level. Fetal survival was not affected. Mean fetal weight was significantly decreased after exposure to all 3 dose levels, and delayed skeletal development occurred but was not dose related.
Prenatal ossification in rabbits as indicative of fetal maturity
Authors: Fritz Hans 
Published: June 2005

AbstractDuring the prenatal period of development of the rabbit skeleton (days 21–30) the successive phases of fetal maturity can be distinguished by reference to the progress of ossification, particularly in the distal limbs and sternum. In the present study absent or incomplete ossification of sternebra 5 occurred in 8% of term fetuses. The incidence of anomalies of prenatal ossification of the axial skeleton was 1.9%. The relevance of delayed and disturbed ossification with regard to teratological tests is discussed.
Teratogenic effects of excess glucose on head‐fold rat embryos in culture
Authors: Cockroft D. L. , Coppola P. T. 
Published: June 2005

AbstractRat embryos explanted at nine and one‐half days of gestation (early head‐fold stages) were cultured for 48 hours in rotating bottles containing rat serum and a gas phase. Addition of 12‐15 mg/ml of D‐glucose to the culture medium resulted in severe abnormalities and retarded development in a high proportion of embryos, whether or not the osmolarity increase brought about by the addition of glucose was corrected. The raised osmolarity, however, increased the frequency and severity of malformations observed. L‐glucose produced no abnormalities, though embryonic development was retarded.
A comparison of the distribution, metabolism and excretion of ethylenethiourea in the pregnant mouse and rat
Authors: Ruddick Joseph A. , Newsome W. H. , Iverson F. 
Published: June 2005

AbstractPregnant mice and rats were treated by stomach intubation on day 15 of gestation with 240 mg/kg of ethylenethiourea (ETU) made up in part with radiolabeled ETU. Animals were sacrificed at specific times post‐treatment, and maternal tissues, fetus, urine and feces were collected for determination of radioactivity. Maternal and fetal tissue levels of ETU were similar at three hours post treatment; thereafter, the mouse (maternal and fetus) showed much less ETU than the rat. The t½ of ETU elimination from the maternal blood was 9.4 and 5.5 hours for the rat and mouse, respectively. Analysis of urine by thinlayer chromatography and radiochromatography revealed that the mouse and rat metabolized ETU by different pathways. Furthermore, the mouse is able to metabolize ETU to a greater extent than the rat.
Translocation heterozygosity in a malformed piglet and its normal littermates
Authors: Miyake Yoh‐Ichi , Kawata Keiichiro , Ishikawa Tsune , Umezu Masatoshi 
Published: June 2005

AbstractA translocation with centric fusion between the Nos. 13 and 17 acrocentric chromosomes was described in a malformed female piglet and three phenotypically normal littermates by the G‐banding staining technique. Since the translocation was heterozygous, the chromosome number was 37. The differences between the translocation of the present cases and those previously reported in the domestic swine species, as well as in some wild pigs, are mentioned.
Teratogenic effects of combined administration of ethylenethiourea and nitrite in mice
Authors: Teramoto S. , Saito R. , Shirasu Y. 
Published: June 2005

AbstractTeratogenic potential of ethylenethiourea (ETU) was investigated in SLC‐ICR mice after its reaction with sodium nitrite. ETU was given orally in dose of 400 mg/kg on various days of pregnancy in combination with 200 mg/kg NaNO2 at varied intervals. When NaNO2 was given to females immediately after their treatment with ETU on day 6 or 8 of pregnancy, fetal survival was significantly decreased. Various types of malformations were observed in the living fetuses from mothers treated on day 6, 8, or 10 of pregnancy, but not on day 12. The teratogenicity disappeared when NaNO2 was given 2 h after the treatment with ETU.
Maternal fever and neural tube defects
Authors: Layde Peter M. , Edmonds Larry D. , Erickson J. David 
Published: June 2005

AbstractIt has been proposed that hyperthermia in the pregnant woman is associated with neural tube defects in her offspring. We analyzed retrospective interview data for a maternal history of probable febrile illness during the first trimester of pregnancy among mothers of infants with anencephaly or spina bifida. There were two control groups—mothers of infants with Down syndrome and mothers of infants with cleft lip or palate. With the Down syndrome group serving as controls, the incidence of febrile illness among mothers of all infants with neural tube defects was significantly elevated. With the cleft group as controls, the fever incidence was not significantly increased in the neural tube defect groups. When the combined cleft and Down syndrome controls were used, only mothers of the spina bifida group had an elevated fever incidence. Epidemiologic data suggest an association of maternal fever during pregnancy with neural tube defects in the offspring.
Effect of phenytoin on maternal heart rate in A/J mice: Possible role in teratogenesis
Authors: Watkinson William P. , Millicovsky Guillermo 
Published: June 2005

AbstractPhenytoin (diphenylhydantion, Dilantin®, PHT), an anticonvulsant and antiarrhythmic drug, is teratogenic to A/J mice, producing an increased incidence of cleft lip with or without cleft palate [CL(P)] and cardiac defects. Although its mechanism of teratogenic action remains unclear, one possibility may involve uterine ischemia resulting from an exaggerated depressant effect on maternal cardiovascular function. To test this hypothesis, the heart rate response of susceptible A/J and resistant C57B1/6J mice was monitored following intraperitoneal injection of doses of PHT of known teratogenic potential.Heart rate (HR) was obtained electrocardiographically from unanesthetized, pregnant mice on day 10 of gestation via previously implanted subcutaneous electrodes. The HR of A/J mice was significantly depressed relative to vehicle‐injected controls following doses of 40, 60, and 75 mg/kg, with the greatest effect occurring in the high‐dose group. In C57B1/6J mice, the HR response of the group treated with 75 mg/kg was not different from that of the vehicle‐treated controls. At the same dose level, the depression of HR of A/J mice was significantly greater in magnitude and duration than that of C57B1/6J mice.A proposed maternally mediated mechanism of CL(P) in A/J mice involving low placental/embryonic oxygen delivery is discussed. The results of the present study indicate the potential significance that changes in maternal physiology may have on embryonic development.
Monozygotic twin aborted fetuses discordant for holoprosencephaly/synotia
Authors: Machin G. A. , Sperber G. H. , Wootliffe J. 
Published: June 2005

AbstractA pair of monozygotic twin fetuses aborted at 15 weeks were found to be discordant for holoprosencephaly and synotia. They were studied grossly, radiologically, and histologically. Features of first brancial arch dysplasia (synotia, agnathia, and astomia) and holoprosencephaly (absent ethmoid bone and Rathke's pouch) observed in one twin were contrasted with minimal dysmorphology in the co‐twin. Some evidence of the twin transfusion syndrome was also apparent, perhaps contributing to the twins' spontaneous abortion.
Developmental toxicity of the cyanogenic glycoside linamarin in the golden hamster
Authors: Frakes Robert A. , Sharma Raghubir P. , Willhite Calvin C. 
Published: June 2005

AbstractCassava, a staple food in many tropical countries, has been suspected as a cause of human congenital defects. Ingestion of the material during pregnancy has been reported to induce limb defects, microcephaly, open eye, and growth retardation in rats. Linamarin is a natural cyanogenic glycoside that occurs in high concentrations in cassava. In the present study, pregnant hamsters received an oral dose of 70, 100, 120 or 140 mg/kg linamarin or an equivalent volume of isotonic saline during the early primitive streak stage of gestation. A dose of 120 or 140 mg/kg of the glycoside was associated with an increased incidence of vertebral and rib anomalies as well as the production of encephaloceles in the offspring. These larger doses of linamarin also resulted in obvious maternal toxicity. Linamarin treatment had no effect on fetal body weight, ossification of fetal skeletons, embryonic mortality, or litter size. Although ingestion of the cyanogenic glycoside was associated with a significant teratogenic response, the effects occurred only at doses that elicited signs of maternal intoxication.
Pathogenesis of the mouse forelimb deformity induced by acetazolamide: An electron microscopic study
Authors: Datu Abdul Razak , Nakamura Harukazu , Yasuda Mineo 
Published: June 2005

AbstractScanning electron microscopic observations after removal of the epidermis from developing limb buds reveal a fine mesenchymal cell process meshwork (CPM). The relationship between apical ectodermal ridge (AER) development and CPM density was investigated and related to the postaxial reduction deformities induced by acetazolamide (AA). AA was given orally to pregnant mice at 9 A.M. and 4 P.M. of day 9 and 9 A.M. of day 10 (VP = 0) in a dose of 1,000 mg/kg. Forelimb ectrodactyly, especially on the right, was the most common deformity observed. Scanning electron microscopic observations showed that the AER in AA‐treated right forelimb buds did not extend postaxially as far as that in controls. The postaxial region with the hypoplastic AER became defective. Scanning and transmission electron microscopic observations revealed that in control and treated right forelimb buds, the CPM underneath the typical AER was sparser than that underneath the dorsal or ventral non‐ridge epidermis. However, in treated right forelimb buds, the CPM underneath a hypoplastic AER was denser than that underneath the normal AER. These findings suggest that AA‐induced deformity results from a disturbance of the AER‐mesenchymal interactions.
Developmental toxicity of aflatoxin B1 in the rodent embryo in vitro: Contribution of exogenous biotransformation systems to toxicity
Authors: Geissler Francis , Faustman Elaine M. 
Published: June 2005

AbstractAflatoxin B1 (AFB1) is a known carcinogen and developmental toxin in various species of mammals, birds, amphibians, and fish. AFB1 requires metabolic activation (biotransformation) to the 2,3‐epoxide metabolite for carcinogenicity; however, it is unknown if biotransformation is a prerequisite for AFB1 embryotoxicity. Cultured day 10 rat embryos were exposed to AFB1 alone and AFB1 in the presence of cofactors and hepatic S9 fractions from adult male rats induced with either phenobarbital or 3‐methylcholanthrene. Under these different culture conditions qualitatively similar patterns of malformation were seen in all embryos exposed to AFB1. At culture concentrations of 15 μM or greater, AFB1 produced abnormalities in neural tube development in a concentration‐dependent manner. The presence of hepatic S9 fractions had no effect on the ability of AFB1 to produce dysmorphogenesis in vitro or on the spectrum of malformations elicited. However, the addition of hepatic S9 fractions did greatly enhance the embryolethality of AFB1. This enhancement was greater with phenobarbital‐ than 3‐methylcholanthrene‐preinduced hepatic S9 fractions. Our results suggest that separate chemical mediators may be responsible for the embryolethal and dysmorphogenic effects of AFB1 observed in day 10 rat embryos in vitro. We found that the embryolethality of AFB1, but not the dysmorphogenicity, could be greatly modulated by exogenous biotransformation.
Brain changes in rats induced by prenatal injection of methylazoxymethanol
Authors: Tamaru Masao , Hirata Yukari , Nagayoshi Michiko , Matsutani Tenhoshimaru 
Published: June 2005

AbstractVarious doses (0, 1, 5, 10, 15, 20, or 25 mg/kg) of methylazoxymethanol acetate (MAM), a potent alkylating agent, were injected singly into pregnant rats intraperitoneally on day 15 of gestation. Relationships between brain weights and neurochemical changes in the cerebral hemispheres (CHs; cerebral cortex and subjacent white matter, hippocampus, amygdala) and remainder of the brain (BGDM; basal ganglia, diencephalon, and mesencephalon) were examined at 60 days of age in offspring; varying degrees of microencephaly were observed. Dose‐dependent reductions in the weights of CH and BGDM were observed. Reductions in total DNA content positively correlated with decreases in brain weights also observed. Dose‐dependent elevations of noradrenaline (NA) and dopamine (DA) were observed in CH at MAM levels 10 mg/kg and above; dose‐dependent elevations of 5‐hydroxytryptamine (5‐HT) were observed at 15 mg/kg and above; and in BGDM at 20 mg/kg and above dose‐dependent elevations for NA and 5‐HT were observed; dose‐dependent elevations at 15 mg/kg and above were observed for DA. Monoamine concentrations were negatively correlated with brain weights or total DNA contents. NA and DA concentrations increased to the extent of approximately 1.3 times of control at a time when an 18% loss of CH weight was noted in animals treated with 10 mg/kg MAM. It is suggested that the above variables might be appropriately sensitive neurochemical markers for detecting minor developmental anomalies in the brain.
Valproic acid developmental toxicity and pharmacokinetics in the rhesus monkey: An interspecies comparison
Authors: Hendrickx A. G. , Nau H. , Binkerd P. , Rowland J. M. , Rowland J. R. , Cukierski M. J. , Cukierski M. A. 
Published: June 2005

AbstractThis study was undertaken to assess the developmental toxicity and drug distributional and metabolic characteristics of prenatal valproic acid (VPA) exposure in rhesus monkeys. Oral administration of 20–600 mg/kg/ day VPA (approximately 1–15 × human therapeutic dose) to 33 animals on variable gestational days (GD) during organogenesis resulted in dose‐dependent developmental toxicity manifested as increased embryo/fetal mortality, intrauterine growth retardation, and craniofacial and skeletal defects. Biphasic plasma elimination curves were observed for total and free VPA on the first (GD 21) and last (GD 50) days of treatment in the 100‐ and 200‐mg/kg/day dose groups. VPA exhibited dose‐independent elimination kinetics at the plasma concentrations observed in this study. There was no significant change in pharmacokinetic parameters (maternal plasma elimination rate, area under the curve, peak plasma concentration) between the first and last days of treatment at either dose level. Placental transfer studies indicated that embryos were exposed to half the free VPA concentrations present in maternal plasma on GD 37. Comparisons of interspecies sensitivity to VPA‐induced developmental toxicity in the mouse, rat, monkey, and man are made.