bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early sialylation on N‐CAM in splotch neural tube defect mouse embryos
Authors: Neale Sondra A. , Trasler Daphne G. 
Published: June 2005

AbstractThe splotch (Sp) mutant mouse is a model for neural tube defects and Waardenburg syndrome type I. The neural tube defects that arise in sp, which include spina bifida and exencephaly, are though to be caused by a change in the timing of the cellular events which are taking place during neurulation. Cell adhesion molecules are strongly implicated in a variety of cell‐cell interaction throughout development, thus the neural cell adhesion molecule (N‐CAM) may play a role in neural tube formation and closure. The N‐CAM in day 9Sp embryos is altered showing a heavy 200 kD species rather than the 180 and 140 kD isoforms which are normally present at that developmental stage [Moase and Trasler (1991) Development 113: 1049–1058]. These N‐CAM isoforms normally become modified post‐translationally by the addition of α‐2,8 linked polysialosyl (PSA) units beginning at gestational day 11. Sp/Sp, Sp/+, and +/+ embryos were examined by Western blot analysis with an antibody (mAb 5A5 ) which specifically recognizes PSA residues on N‐CAM. Mutant and heterozygote embryos display a sialylated N‐CAM form at 20, 14, and 12 somite‐stages which is absent in controls. Enzymatic removal of PSA on N‐CAM resulted in a reduction of the 200 kD species to the expected 180 and 140 kD PSA–free N‐CAM isoforms. These result demonstrate that PSA exits on N‐CAM at an abnormally early developmental stage which results in the observed 200 kD species, and suggest that the sp gene is involved in the regulation of expression or the post‐translational modification of N‐CAM. © Wiley‐Liss, Inc.
Selenium kinetics, placental transfer, and neonatal exposure in cynomolgus macaques (Macaca fascicularis)
Authors: Hawkes Wayne Chris , Willhite Calvin C. , Omaye Stanley T. , Cox Douglas N. , Choy Wai Nang , Tarantal Alice F. 
Published: June 2005

AbstractForty pregnant cynomolgus macaques were treated daily from gestational day 20 to 50 by nasogastric intubation of 0, 25, 150, or 300 μg selenium asL‐selenomethionine/kg body weight. In each group, 7–8 pregnancies were terminated by hysterotomy at gestational day 100 ± 2 and the fetuses were examined, while 2–3 pregnancies in each group were allowed to proceed to term. Selenium and soluble glutathione peroxidase were measured in: maternal, neonatal, and fetal plasma and erythrocytes; fetal kidney, liver, muscle, and placenta; and maternal breast milk. The area under the multidose maternal plasma selenium concentration:time curve, the maximum maternal plasma selenium concentration, and the maternal urinary selenium excertion rates were proportional to theL‐selenomethionine dose. Selenium concentrations in all fetal and neonatal tissues were also proportional to maternalL‐selenomethionine dose. Glutathione peroxidase was affected only in maternal erthrocytes, fetal kidney, and neonatal plasma. The selenium concentration in fetal plasma was an average 33% of that in maternal plasma. Although selenium concentration in macaque milk were doubled by the highest does, intrauterine selenium accumulation accounted for the majority of the neonatal selenium body burden. Despite the elevated selenium concentrations in fetal tissues, neonatal blood, and milk, no deleterious effects on neonates were observed. There results suggest that primate fetuses are well protected against selenium toxicity arising from high maternalL‐selenomethionine intakes. © 1994 Wiley‐Liss, Inc.
Placental teratoma with three‐germ layer differentiation
Authors: Sironi Maria , Declich Paolo , Isimbaldi Giuseppe , Monguzzi Alberto , Poggi Giuseppe 
Published: June 2005

AbstractA rare case of placental teratoma is described. Major features were the presentation as a pedunculated mass from the fetal surface of the placenta, the mixture of different tissues derived from all three germ layers (skin with dermal appendages, ganglion‐like cells, and nervous structures, gut structures, osteocartilagineous and smooth and striated muscle), and the absence of segmental organization. © 1994 Wiley‐Liss, Inc. © 1994 Wiley‐Liss, Inc.
In vitro embryotoxicity of the cysteine proteinase inhibitors benzyloxycarbonyl‐phenylalanine‐alanine‐diazomethane (Z‐Phe‐Ala‐CHN2) and benzyloxycarbony1‐phenylalanine‐phenylalanine‐diazomethane (Z‐Phe‐Phe‐CHN2)
Authors: Ambroso Jeffrey L. , Harris Craig 
Published: June 2005

AbstractThis study makes use of whole embryo culture to investigate the potential embryotoxicity of benzyloxycarbonyl‐phenylalanine‐alanine‐diazomethane (Z‐Phe‐Ala‐CHN2) and benzyloxycarbonyl‐phenylalanine‐phenylalanine‐diazomethane (Z‐Phe‐Phe‐CHN2), two low molecular weight, active site‐directed and irreversible inhibitors of the lysosomal cysteine proteinases. Peptidyl diazomethanes are the most specific inhibitors available for lysosomal cysteine proteinases and can be hypothesized to interrupt visceral yolk sac (VYS)‐mediated nutrition during early organogenesis. When added directly to the culture medium of gestational day 10–11 rat conceptuses, both compounds inhibited lysosomal cysteine proteinase activity in the VYS in a concentration‐dependent fashion that correlated with the degree of embryotoxicity observed. Z‐Phe‐Ala‐CHN2 and Z‐Phe‐Phe‐CHN2 were also found to increase the protein content of the VYS, even though all other conceptal growth parameters decreased. This effect was dependent on the serum content of the culture medium and the exposure time. Histological examination of Z‐Phe‐Ala‐CHN2‐treated conceptuses revealed a dramatic increase in the size and number of vacuoles in the VYS endoderm epithelium, suggestive of inhibition of VYS proteolysis. At the same time, excessive cell death was observed throughout the neuroepithelium and in specific regions of the mesenchyme of the corresponding embryos. This cell death manifested morphological characteristics of apoptosis and could be detected by supravital staining with Nile Blue Sulphate. These findings provide additional evidence in support of the hypothesis that lysosomal cysteine proteinases play a critical role in VYS‐mediated histiotrophic nutrition and suggest that peptidyl diazomethanes may be useful in further characterization of these enzymes. The possible direct effects of these inhibitors on embryonic cells and the relationships between interruption of VYS‐mediated nutritional processes and embryonic cell death are discussed. © 1994 Wiley‐Liss, Inc.
Cell death and cell cycle perturbation in the developmental toxicity of the demethylating agent, 5‐Aza‐2′‐deoxycytidine
Authors: Rogers John M. , Francis B. Magnus , Sulik Kathleen K. , Alles Ajit J. , Massaro Edward J. , Zucker Robert M. , Elstein Kenneth H. , Rosen Mitchell B. , Chernoff Neil 
Published: June 2005

AbstractDNA methylation is a probable mechanism for regulating gene expression, and alterations in methylation may significantly affect embryonic development. We administered the cytidine analogue 5‐aza‐2′‐deoxycytidine (dAZA), a specific and potent demethylator of DNA, to pregnant mice to determine its teratogenicity and effects on embryonic cell death and cell cycle. Groups of females were dosed intraperitoneally on gestation day 10 with doses of 0.05‐3 mg/kg dAZA and killed at 4, 8, or 28 hr later. Two embryos per litter were immediately stained with Nile blue sulfate (NBS) to identify areas of cell death; the remaining embryos were frozen and stored for subsequent flow cytometric (FCM) analysis of the cellular DNA synthetic cycle in limb buds. A dose‐related accumulation of cells in the S and G2/M phases was observed at 4 and 8 hr after maternal dosing. S‐phase accumulation was the most sensitive indicator of effect; a dose‐related increase in the percentage of hindlimb bud cells in S‐phase was evident at all dosages 4 hr after maternal dosing. By 28 hr postdosing, a normal cell cycle phase distribution was observed at doses of < 0.3 mg/kg. However, cell cycle perturbations persisted at higher dosages. NBS staining demonstrated increased cell death in areas of rapid cell division, indicative of replication‐associated cytotoxicity, at doses of ≥0.1 mg/kg. Observation of litters from additional dams killed at term revealed that at dosages of ≥0.3 mg/kg, cleft palate and hindlimb defects were significantly elevated. In addition, above 0.3 mg/kg, fetal weight was significantly decreased. Embryonic mortality did not increase significantly at dosages of < 2 mg/kg but reached 100% at 3 mg/kg. Vertebral and pelvic girdle malformations were seen at doses of 2l mg/kg. These results indicate that the demethylating agent dAZA perturbs embryonal DNA synthesis and results in the death of rapidly proliferating cells. The observation of cell cycle perturbations and cell death at dosages below those producing frank terata indicate some ability of the embryo to compensate for and/or repair dAZA‐induced cellular damage. © 1994 Wiley‐Liss, Inc.This article is a US Government work and, as such, is in the public domain in the United States of America.
Maternal restraint stress‐enhanced teratogenicity of all‐trans‐retinoic acid in CD‐1 mice
Authors: Rasco Jane F. , Hood Ronald D. 
Published: June 2005

AbstractThe present study combined maternal restraint stress with a teratogenic agent, all‐trans‐retinoic acid (†RA). Five treatment groups were used initially: (1) vehicle (corn oil) control [C],(2) food/water‐deprived [FWD], (3) †RA only [†RA](4)restraint only [R], and (5) †RA plus restraint [†RA+R] Mated CD‐1 mice in groups 3 and 5 were given 20 mg/kg †RA po. Mice in groups 4 and 5 were restrained in the supine position for 12 hr (9:00 a.m. to 9.00 p.m.), and the FWD group mice were deprived during the same time period. The †RA+R mice were dosed immediately prior to the 12‐hr restraint period. All treatments were administered on gestation day (GD) 9 (copulation plug = day 1). On GD 18, all females were killed and subjected to teratological examination. The incidences of resorptions, short tails, bent tails, fused ribs, and fused vertebrae were significantly increased in the †RA+R group, in comparison with all other groups. Spina bifida was observed only in the †RA+R group. The current results, combined with those of earlier studies with other agents, support the likelihood that maternal stress can exacerbate adverse effects of chemical teratogens on mouse development.
Reduced recurrence of orofacial clefts after periconceptional supplementation with high‐dose folic acid and multivitamins
Authors: Tolarova Marie , Harris John 
Published: June 2005

AbstractTo assess effects of periconceptional multivitamin and folic‐acid supplementation on recurrence of cleft lip with or without cleft palate (CL±P), we prospectively evaluated 221 pregnancies in women at risk of a child with CL±P. The 10‐step protocol included multivitamin supplementation with SPOFAVIT (A, B1, B2, B6, C, D3, E, nicotinamide, calcium pantothenicum) and folic acid (10 mg/day), beginning ≥2 months before planned conception and continuing for ≥3 months thereafter. A comparison group comprised 1,901 women at risk of a child with CL±P, who received no supplementation and gave birth within the same period as the study group. In the supplemented group, 3 of 214 informative pregnancies ended with infants with CL±P, a 65.4% decrease (observed versus expected value ‐5.67; P = 0.031, Fisher's exact test); the expected value of 8.7 was calculated based on the incidence of cleft among first‐degree relatives among the comparison group. Subset analysis by proband's sex, severity of CL±P, and both variables showed highest supplementation efficacy in probands with unilateral cleft (82.6% decrease, P = 0.024, Fisher's exact test). No efficacy was observed for female probands with bilateral CL±P. Generally, efficacy was greater for subgroups with unilateral than with bilateral cleft and for male than female probands. These findings confirm the need for a randomized, double‐blind, controlled multicenter trial to establish whether periconceptional vitamin supplementation, prevent CL±P and, if it does, whether the effective agent is folic acid or multivitamins, or both combined. © 1995 Wiley‐Liss, Inc.
Developmental toxicity of formate and formic acid in whole embryo culture: A comparative study with mouse and rat embryos
Authors: Andrews James E. , Ebron‐McCoy Marian , Kavlock Robert J. , Rogers John M. 
Published: June 2005

AbstractAcute methanol (MeOH) toxicity in primates is attribute to the conversion of MeOH to formate and the resulting acidosis. MeOH has been shown to be developmentally toxic in mice and rats both in vivo and in vivo, but rodents neither accumulate formate nor develop acidosis after MeOH exposure. To further assess the potential human developmental effects of sodium (Na) formate and formic acid in rodent whole embryos were cultured (WEC). Day 9 rat embryos were cultured for 24 or 48 hours and day 8 mouse embyos were cultured for 24 hours in the presence of Na‐formate or formic acid. Rat and mouse embryos exposed to either agent for 24 hours exhibited a trend toward reduced growth and development and the number of abnormalities increased at the higher concentrations. Rat embryos exposed for 48 hours to either Na‐formate or formic acid showed a trend toward reduced growth and development with increasing concentrations. The anomalies abserved in both species after exposure to either compound were primarily open anterior and posterior neuropore with less frequent incidence of rotational defects, tail anomalies, enlarged pericardium and delayed heart development. Exposure to Na‐formate or formic acid for comparable periods of time results in comparable degrees of embryotoxicity at concentrations (mMolar) at least 4‐fold lower than those previously reported for methanol exposure. © 1995 Wiley‐Liss, Inc. This article is a US Government work and, as such, is in the public domain in the United States of America.
Antisense targeting of Engrailed‐1 causes abnormal axis formation in mouse embryos
Authors: Sadler T. W. , Liu Edison T. , Augustine Karen A. 
Published: June 2005

AbstractAntisense oligonucleotide targeting ofengrailed‐1 (En‐1) in early somite mouse embryos resulted in reducedEnprotein levels and produced abnormalities of the brain, face, and heart and shortening of the embryonic axis (caudal dysgenesis). Defects of the brain and limbs were consistent with abnormalities observed in null mutant mice described by other investigators. Abnormalities of the face and heart may be related to alterations in neural crest cells. Caudal dysgenesis suggested a role forEn‐1in axis formation and this hypothesis was supported by results showing thatEn‐1 protein and mRNA are present in the primitive streak. Thus, in addition to participating in the signaling pathway for brain and limb development, En‐1 appears to play a role in patterning the embryonic axis. © 1995 Wiley‐Liss, Inc.
Platelet‐derived growth factor receptor alpha subunit deleted Patch mouse exhibits severe cardiovascular dysmorphogenesis
Authors: Schatteman Gina C. , Motley S. Tim , Effmann Eric L. , Bowen‐Pope Daniel F. 
Published: June 2005

AbstractPath (Ph) mice, whose platelet‐derived growth factor receptor alpha subunit (αPDGFR) gene has been deleted, have been used to elucidate requirements for αPDGFR for normal murine development. In this report we evaluate the role of αPDGFR in cardiovascular development by using in situ hybridization to follow the changing pattern of αPDGFR expression in cardiovascular tissues after embryonic day 13, and comparing this pattern with the pattern of cardiovascular defects observed in homozygous Ph mutants. Both mesodermally derived and neural crest‐derived components of the cardiovascular system are severely dysmorphic in Ph/Ph embryos and those structures most severely affected are those that normally express αPDGFR mRNA at the highest levels and for the longest duration. Ph/Ph vessels appear to be lined with a normal endothelium, but contain a reduced number of smooth muscle cells and are fragile during processing for histology. The myocardium is thin, the heart is small and dysmorphic, the valves are malformed, and the interventricular and interatrial septa of the heart are defective. In the outflow tract, the spectrum of defects includes both persistent truncus arteriosus and double outlet right ventricle. This pattern of abnormalities is consistent with the hypothesis that deletion of αPDGFR results in a functional ablation of cranial neural crest cells, and that mesodermally derived components of the vascular system also require αPDGFR. © 1995 Wiley‐Liss, Inc.
Programmed cell death and N‐acetoxy‐2‐acetylaminofluorene‐induced apoptosis in the rat embryo
Authors: Thayer Jeanette M. , Mirkes Philip E. 
Published: June 2005

AbstractN‐acetoxy‐2‐acetlylaminofluorene(N‐Ac‐AAF) is an alkylating agent that forms DNA adducts at C‐8 is guanine and causes single strand breaks. It has abnormal development have not been investigated. Previous studies have indicated that other DNA alkylating agents cause cell death during embryonic development although the types of cell death were not characterized. Using a whole embryo culture system, gestation day 10 rat embryo were exposed to several concentrations (5, 50 and 200 μg/ml)of N‐Ac‐AAF at several times points after expire was begun (5,10,24 hours), the embryos were removed from culture from culture and examined to identify location, type and quantity of cell death, relative to programmed cell death observed in control embryos. Vital staining with Nile blue sulphate revealed that the location of N‐Ac‐AAf‐ include cell death included the forebrain region, tail and areas of programmed cell death Examination of tissue section from both control and treated embryos indicated that the location of apoptotic cell death revealed by in situ DNA nick end ‐labelling was generally consistent with the cell death pattern observed by vital staining of whole embryos. Agarose gel analyses indicated that all concentration of N‐Ac‐AAF caused DNA fragmentation, and Quantification demonstrated a dose response. Examination of treated embryos (50 and 200μg/ ml) by transmission electron microscopy revealed that, by 5 hours after exposure, cells with class, ultrastructural features of apoptosis were present. In conclusion, multiple method have all indicated that, regardless of exposure level, apoptosis was the predominant from of cell death. Because opotosis also occurs in developmental cell death, it is possible that apotosis induced by N‐Ac‐AAF is due to an alternation in cell fate via premature or ectopic induced of the cell death program. © 1995 Wiley‐Liss, Inc.
Utility of fluorescence microscopy in embryonic/fetal topographical analysis
Authors: Zucker Robert M. , Elstein Kenneth H. , Shuey Dana L. , Ebron‐Mccoy Marian , Rogers John M. 
Published: June 2005

AbstractFor topographical analysis of developing embryos, investigators typically rely on scanning electron microcopy (SEM) to provide the surface details not attainable with light microscopySEM is an expensive and time consuming technique, however, and the preparation procedure may alter morphology and leave the specimen friable. We report that by using a high‐resolution compound epilfluorescence microscope with inexpensive low‐power objectives and the flurochrome acridine orange, we were able to obtain surface image of fixed or fresh whole rat embryos and fetal palates of considerably greater topographical detail than those obtained using routine light microscopy. Indeed the resulting high‐resolution image offered not only superior qualitative documentation of morphological observation, but the capability for detailed morphometry via digitization and computer‐assisted image analysis. © 1995 Wiley‐Liss, Inc.
Induction of apoptosis and cathepsin D in limbs exposed in vitro to an activated analog of cyclophosphamide
Authors: Moallem S. Adel , Hales Barbara F. 
Published: June 2005

AbstractApoptosis, a form of active cell death, plays a role during normal limb development. The present study was done to test the hypothesis that the teratogen cyclophosphamide, an alkylating agent and commonly used anticancer drug, produces malformations by disturbing the regulation of apoptosis in the limb. The effects of a preactivated analog of cyclophosphamide, 4‐hydroperoxycyclophosphamide, on limb development and on apoptosis in the limb were determined in vitro. Cathepsin D is a lysosomal protease which is induced in tissues undergoing destruction by apoptosis. To further examine the process of apoptosis in the limb, the effects of 4‐hydroperoxycylophosphamide exposure on cathepsin D protein concentration and on the immunolocalization of cathepsin D in limb buds were assessed. Limb buds from gestational day 12 mice were excised and cultured in roller bottles in a chemically defined medium for up to 6 days. The addition of 4‐hydroperoxycyclophosphamide (1 or 10 μg/ml) to the culture medium produced time‐ and concentration‐dependent limb malformations. Electrophoresis of the DNA extracted from both control and treated limbs revealed a DNA fragmentation pattern characteristic of apoptosis. Limbs cultured in the control medium showed a “DNA ladder” only after 72 hours in vitro; however, those in the drug‐treated groups showed fragmentation within 12 hours of drug exposure. Acridine orange staining and examination of cell ultrastructure with the electron microscope further confirmed that apoptotic cell death in the interdigital areas was accelerated in drug‐exposed limbs. The relative abundance of cathepsin D in limbs exposed to 4‐hydroperoxycyclophosphamide for 24 hours was increased compared to control limbs. Using immunohistochemical staining at the light microscope level, the cathepsin D protein in control limbs was localized mainly to the interdigital and apical ectodermal ridge areas; staining in these areas was increased in limbs exposed to 4‐hydroperoxycyclophosphamide. Using immunogold electron microscopy, cathepsin D immunoreactivity was found to be localized in phagocytosed apoptotic bodies; this observation suggests that it is the process of phagocytosis which induces cathepsin D. Thus, exposure to 4‐hydroperoxycylophosphamide increased apoptosis in the interdigital areas and apical ectodermal ridge of mouse limb buds in vitro. Moreover, cathepsin D may play an important role in mediating the phagocytosis of apoptotic bodies in the teratogen‐exposed limbs. ©1995 Wiley‐Liss, Inc.
Descriptive epidemiology of alimentary tract atresia
Authors: Harris John , Källén Bengt , Robert Elisabeth 
Published: June 2005

AbstractA study has been made on certain epidemiological characteristics of infants with alimentary tract atresia: esophageal atresia, small and large gut atresia, and anal atresia. Data were collected from three malformation registries and represent a material of more than 4.5 million births. A total of 3,550 infants with alimentary atresia were identified corresponding to a total rate of about 8 per 10,000 births. In 167 infants (4.7%) more than one of the major atresia types were present simultaneously. Racial differences were found (based on data from California) for esophageal atresia where whites had a higher rate than other races. For gastrointestinal atresia, a high rate in blacks was found, while no differences between races were seen for anal atresia. Also, differences in registered rates between the three programs were found, at least partly explainable by different ascertainment. The different forms of atresia were compared from the point of view of sex ratio, twinning rate, maternal age and parity distribution, presence of chromosome anomalies, and types of associated malformations. The pathogenesis and etiology of the various types of atresia are discussed based on these observations. The conclusion is that although undoubtedly other pathogenetic mechanisms may exist for gastrointestinal atresia, a substantial proportion of all infants with alimentary atresia had their malformations as a result of early disturbances of intestinal morphogenesis. Within each subgroup, apparently different etiologies may exist, resulting in differences in epidemiological characteristics. © 1995 Wiley‐Liss, Inc.