bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toxicity of the methyl isocyanate metabolite S‐(N‐methylcarbamoyl)GSH on mouse embryos in culture
Authors: Guest Ian , Baillie Thomas A. , Varma Daya R. 
Published: June 2005

AbstractMethyl isocyanate, the chemical involved in the 1984 accident at Bhopal, India, forms a labile conjugate, S‐(N‐methylcarbamoyl)GSH (SMG), by way of a reversible reaction with GSH. We studied the toxicity of SMG on mouse embryos explanted on day 8 of gestation and cultured in rat serum for 42 hr. SMG caused concentration‐dependent decreases in growth and development over the range 0.1–2 mM, without causing significant mortality. At a concentration of 2 mM, SMG completely arrested embryo development, but heartbeat was absent in only one of nine embryos at 42 hr. At a concentration of 0.25 mM, SMG reduced embryo size to 75% and protein content to 63% of the control; 18% of embryos failed to rotate. At this concentration (0.25 mM), which was selected for all other studies, spinal kinks and somite pair distortion in the region of the forelimb were evident in 38% of embryos; no other abnormalities were noted. DNA content of and thymidine incorporation by embryos and yolk sacs was reduced by SMG, although this was more pronounced in the yolk sac than in embryos. At subtoxic concentrations, the L‐cysteine precursor (−)‐2‐oxo‐4‐thiazolidine‐carboxylic acid did not, but GSH did, inhibit embryotoxicity of SMG. It is concluded that SMG exerts embryotoxic and dysmorphogenic effects and may contribute to systemic toxicity of methyl isocyanate. © 1992 Wiley‐Liss, Inc.
Morphological and physiological correlates of unilateral agenesis of the urogenital system in young ovariectomized ACI rats
Authors: Vassilacopoulou Dido , Boylan Elizabeth S. 
Published: June 2005

AbstractACI rats are distinguished by a polygenic trait resulting in unilateral agenesis of the urogenital system in 20–30% of animals of both sexes. This report details additional features, both morphological and physiological, which distinguish ACI rats with unilateral agenesis of the reproductive and urinary tracts from the majority of ACI rats that have intact urogenital systems. Young female ACI rats were ovariectomized at 34 days of age and sacrificed 19 days later. A preliminary determination of the urogenital morphology was made at the time of ovariectomy and then confirmed by careful abdominal inspection at necropsy. Data on the time of vaginal opening were obtained at selected intervals prior to sacrifice. At necropsy, the mammary glands were removed and were prepared as stained whole mounts for morphological evaluation; the remaining portions of the reproductive tracts were excised, weighed, fixed, and sectioned for microscopic examination. A majority of animals with unilateral agenesis had mammary glands that had higher degrees of glandular proliferation than the mammary glands of intact rats. Unilateral agenesis animals also possessed significantly thicker and heavier uterine horns, despite having been ovariectomized. Furthermore, rats with unilateral agenesis were found to have an earlier time of vaginal opening than that of their intact counterparts. These features of ovariectomized ACI rats with unilateral agenesis are consistent with an active, extra‐ovarian source of endogenous estrogen. Further investigation of the endocrinological state of animals with unilateral agenesis of the urogenital tract is warranted. Those using this model system for transplacental or endocrinological studies should take into account these distinguishing characteristics of ovariectomized ACI rats with unilateral agenesis when planning experiments and analyzing data from a population of rats with both morphologies. © 1992 Wiley‐Liss, Inc.
Ellagic acid protects rat embryos in culture from the embryotoxic effects of N‐methyl‐N‐nitrosourea
Authors: Frank Anthony A. , Collier John M. , Forsyth Carol S. , Heur Young‐Hun , Stoner Gary D. 
Published: June 2005

AbstractEllagic acid is a naturally occurring plant phenol that has demonstrated anticarcinogenic and antimutagenic acitvity in several test systems. Given the common proposed etiopathogenic processes of mutagenesis, carcinogenesis, and teratogenesis induced by genotoxic chemicals, the present study was initiated to determine whether ellagic acid would protect rat embryos in culture from the teratogenic effects of N‐methyl‐N‐nitrosourea (MNU). Ellagic acid alone (as used in these experiments; 50 μM in DMSO) was not embryotoxic. Ellagic acid (50 μM) significantly (P < 0.01) prevented MNU (75 μM)‐induced effects including mortality (absence of heart beat), abnormal formation of the cephalic neural tube derivatives, and delayed differentiation as assessed by a morphological scoring system. These embryoprotective effects were dose responsive. Sequential treatment of embryos with ellagic acid followed by MNU in fresh media also was embryoprotective with no diminution of effect. The site at which ellagic acid interrupts the critical teratogenic events induced by MNU is apparently within the embryo and/or placenta. This model of chemical embryoprotection may be useful in determining the role of cell death and/or mutation in the teratogenic mechanism of action of methylating agents. © 1992 Wiley‐Liss, Inc.
Prevention of tilorone developmental toxicity with progesterone
Authors: Terry Roger D. , Marks Thomas A. , Hamilton Ramon D. , Pitts Thomas W. , Renis Harold E. 
Published: June 2005

AbstractThe immunomodulator tilorone hydrochloride was administered (gastric intubation) once to time‐pregnant Upj:TUC(SD)spf (Sprague‐Dawley) rats in four experiments. In experiment 1, tilorone (250 or 500 mg/kg) was administered on day 10 of gestation. The dams were killed 4 or 72 hr after dosing. Interferon‐like activity and drug levels were determined in maternal blood, spleen, and thymus, as well as in the embryos. In experiment 2, the test groups received progesterone (2 mg/kg), or tilorone (200 or 400 mg/kg), or progesterone and tilorone. The dams from each group were killed 24 or 48 hr after receiving tilorone. Experiment 3 was similar to experiment 2, except that the dams were killed on gestation day 20. In experiment 4, tilorone (400 mg/kg) was administered on gestation day 17, 18, or 19, and the dams were killed 24 hr after dosing or on gestation day 20. In all four experiments, tilorone‐related maternal toxicity (regardless of whether progesterone also was administered) was observed, as characterized by marked decreases in weight gain, the occurrence of clinical signs, and in experiment 1 by decreased thymus weights, 72 hr postdosing. Dose‐related increases in the mean number of dead embryos and in serum interferon titers occurred 72 hr postdosing. In experiment 2, there was an increase in the number of dams in the 400‐mg/kg (tilorone only) group with dead embryos only, 24 hr postdosing; similar results occurred in both the 200‐ and 400‐mg/kg groups, 48 hr postdosing. However, in the groups that also received progesterone, a partial prevention of such embryolethality was evident. In experiment 3, embryotoxicity again was observed in both tilorone‐treated groups, whereas several of the dams that were also given progesterone through day 19 of gestation experienced at least a partial prevention of the embryolethal effects of tilorone. In experiment 4, no fetotoxicity was observed despite the severe maternal toxicity evident. © 1992 Wiley‐Liss, Inc.
Epidemiology of congenital heart disease in Louisiana: An association between race and sex and the prevalence of specific cardiac malformations
Authors: Storch Thomas G. , Mannick Elizabeth E. 
Published: June 2005

AbstractWe hypothesized that susceptibility to the genetic and environmental factors that disrupt cardiac development is associated with race and sex. To evaluate this hypothesis, we asked whether the prevalence of specific cardiac malformations differs by race and sex. We attempted to include all infants born alive in the State of Louisiana from January 1, 1988, through December 31, 1989, and diagnosed by echocardiography, catheterization and/or autopsy within a year of birth as having one of ten specific cardiac malformations. The prevalence of atrioventricular canal defects (AVCD) per 1,000 live births was significantly higher for black females (.744) compared to black males (.198) and for white females (.414) compared to white males (.116). Complete transposition of the great arteries (TGA) was significantly higher for white males (.559) compared to white females (.122); in contrast, TGA was not significantly different for black males (.198) and black females (.169). Obstructive left heart syndrome (OLHS)—aortic stenosis and/or coarctation of the aorta—was significantly higher for white males (.652) compared to white females (.317); in contrast, OLHS was not significantly different for black males (.264) and black females (.169). Single ventricle (SV) was significantly higher for whites (.202) compared to blacks (.067). We did not find that race and sex were associated with differences in the prevalence of tetralogy of Fallot and hypoplastic left heart syndrome. The numbers of infants with anomalous pulmonary venous return, tricuspid atresia, double outlet right ventricle, or truncus arteriosus were too small to measure an association with race and sex. These results demonstrate that the prevalence of a subset of cardiac malformations differs by race and sex. Selective fetal survival and differential susceptibility to cardiac malformations may be associated with these findings. © 1992 Wiley‐Liss, Inc.
The perception of teratogenic risk of cocaine
Authors: Koren Gideon , Gladstone David , Robeson Christine , Robieux Isabelle 
Published: June 2005

AbstractWhile there has been a substantial increase in recreational use of cocaine by young adults, conclusive evidence for cocaine teratogenicity in humans in lacking, and even those believing the drug is teratogenic agree that the rates are quite small. While counseling pregnant women on their teratogenic risk, it was our impression that there is an unrealistically high perception of reproductive risk of cocaine. We wished to quantify the perception of teratogenic risk of cocaine by the public, physicians, and by pregnant women who were counseled following gestational exposure to the drug. Women taking cocaine during the first trimester of pregnancy (n = 54), controls with post secondary education (n = 30), and physicians (n = 30) were asked, using a visual analogue scale, to quantify the teratogenic risk of cocaine and the tendency to terminate/contiue the pregnancy after first trimester exposure; in the case of the “public” and physicians this was a hypothetical question. Both physicians and the controls perceived cocaine to be teratogenic (13.4 ± 11% risk of major malformations by physicians, and 56.5 ± 22.8% by the “public”). The controls believed cocaine to be as hazardous as thalidomide (57.2 ± 25.6% risk for thalidomide). Asked whether they would wish to terminate such pregnancy in their family, most physicians (56%) and the controls (70%) had a greater than 50% tendency to terminate. In pregnant patients attending Motherisk, the counseling process resulted in a significant decrease in risk perception of cocaine (from 37.5 ± 20.5% to 17.6 ± 14.2% P<0.0005), and a similar decrease in tendency to terminate pregnancy [from 21/54 (38%) with 50% tendency to terminate to 11 (20%); P = 0.0014]. Postnatal follow‐up revealed that eight women terminated pregnancy while the rest had morphologically and developmentally normal babies. An unrealistically high perception of teratogenic risk of cocaine exists among the controls, physicians, and pregnant women. Physicians' erroneous perception may lead them to offer women unjustified terminations of pregnancy after first trimester exposure to cocaine. Counseling these women during the first trimester is effective in preventing termination of many otherwise wanted pregnancies. © 1992 Wiley‐Liss, Inc.
Process of building biologically based dose–response models for developmental defects
Authors: Gaylor David W. , Razzaghi Mehdi 
Published: June 2005

AbstractThe problem of developing biologically‐based dose–response models is addressed for predicting the prevalence of birth defects at low doses of toxic chemicals administered during pregnancy. To illustrate the process of incorporating biological information, a model is postulated to predict the prevalence of cleft palate for a chemical that reduces embryonic/fetal growth, which results in inadequate palatel cells for closure. Experimental bioassay data examining the prevalence of cleft palate in mice exposed to the herbicide 2,4,5‐T are used to illustrate the process. With the limited data available, it is necessary to assume a model for cell growth and the relationship between the cell growth rate parameter and dose of 2,4,5‐T. Also, a relationship between cleft palate prevalence and growth is assumed and then checked with experimental data. The purpose for the paper is not to provide a universal biologically based dose–response model for cleft palate, but rather to demonstrate the extent, and type of information and data required. It remains to be seen if the form of the model is appropriate for chemicals that primarily produce embryo/fetal malformations or death via reduced or delayed cellular growth. © 1992 Wiley‐Liss, Inc.
Neural tube defects without neural crest defects in Splotch mice
Authors: Franz Thomas 
Published: June 2005

AbstractHomozygous Splotch mutant mice (Sp/Sp) die on day 14 of gestation with neural tube defects, curly tail, and malformations of neural crest derivatives. Sp1H mice, which have a radiation‐induced allele of Splotch with a similar phenotype, were used for this study. The neural tube defects are always located in the lumbosacral region and in 50% of the cases also in the region of the hindbrain. In this report, rare cases of neural tube defects and tail defects among the offspring of crosses between Splotch (Sp1H) heterozygotes are presented, which are not associated with a neural crest defect. This suggests that the development of the neural tube and neural crest defects in this mutant is caused by independent mechanisms or is dependent on the dosage of the mutant gene, with different thresholds being pathogenetic in the neural tube and neural crest, respectively. © 1992 Wiley‐Liss, Inc.
Craniometric measurements of craniofacial malformations in the X‐linked hypophosphatemic (Hyp) mouse on two different genetic backgrounds: C57BL/6J and B6C3H
Authors: Gonzalez Cesar D. , Meyer Ralph A. , Iorio Robert J. 
Published: June 2005

AbstractThis study reports data on craniometric measurements in the X‐linked hypophosphatemic (Hyp) mouse on two different genetic backgrounds: C57BL/6J and B6C3H. Heads of normal females “+/+,” normal males “+/Y,” heterozygous mutant females “Hyp/+,” and hemizygous mutant males “Hyp/Y” for each genetic background were examined. Data were collected via skull measurements. On a C57BL/6J background, the neurocranium of mutants “Hyp/+” and “Hyp/Y” was shorter and slightly higher than in normal counterparts. On a B6C3H background, mutant mice “Hyp/+” and “Hyp/Y” were shorter in neurocranial length than in normal counterparts. Viscerocranial height was larger in “Hyp/Y” than in normal counterparts. No differences in neurocranial and mandibular height were found. Mutant mice on a C57BL/6J background were compared to mutant mice on a B6C3H background. No differences in neurocranial length were found. Cranial length was shorter in “Hyp/Y” on C57BL/6J than in “Hyp/+” on B6C3H. Facial length parameters were shorter in “Hyp/Y” on C57BL/6J than in “Hyp/Y” and “Hyp/+” mutant mice on B6C3H. Mandibular length was shorter in “Hyp/Y” on C57BL/6J than in “Hyp/+” on C57BL/6J and both mutant mice (“Hyp/Y” and “Hyp/+”) on a B6C3H background. The results of this study indicate that craniofacial growth is less affected in mutant mice on a B6C3H genetic background than in mutant mice on a C57BL/6J genetic background. © 1992 Wiley‐Liss, Inc.
Nitrofen‐induced congenital diaphragmatic defects in CD1 mice
Authors: Wickman Debra S. , Siebert Joseph R. , Benjamin Denis R. 
Published: June 2005

AbstractIn previous clinical reports, we have documented the association of several morphologic changes with congenital diaphragmatic hernia or, perhaps more appropriately termed, congenital diaphragmatic defect (CDD). These anomalies include decreased cardiac mass with left ventricular hypoplasia in infants with left‐sided CDDs (Siebert et al., '84), enlarged, asymmetric chests (Siebert and Benjamin, '87), and extrathoracic anomalies (Benjamin et al., '88), including urinary tract anomalies and elevated kidney weights in otherwise normal kidneys (Glick et al., '90; Siebert et al., '90). Hypoplastic lungs and hearts and enlarged chests are thought to result from the herniation of abdominal viscera into the thoracic cavity, but for the renal abnormalities, pathogenesis is unclear. The findings are intriguing, for they could mirror unrecognized developmental relationships between the diaphragm, lung, heart, and kidney. In order to further examine these issues and to test the applicability of experimentally produced CDDs to human disease, we administered nitrofen (2,4‐dichlorophenyl‐p‐nitrophenyl ether), an herbicide known to produce diaphragmatic defects in rodents, to time‐mated CD1 mice by gavage feeding on gestational days 8 and 9. Dosages were 200 (low dose) or 500 (high dose) mg/kg body weight, and fetuses were studied on gestational day 18. Diaphragmatic defects occurred in a dose‐response fashion: 0% (0/48) control or sham‐fed, 5% (5/104) in the low‐dose group, and 25% (19/75) in the high‐dose group. Several fetuses with cleft palate, renal agenesis, exencephaly/encephalocele, and/or Di‐George sequence were noted at the high dose, the latter a previously undescribed finding. Diaphragmatic defects were primarily right sided and only associated with herniation of abdominal viscera in animals exposed to 500 mg/kg. Body weight was uniformly decreased and crown‐rump length variably so by nitrofen exposure, while chest diameters were increased. Reduced heart and lung weights and elevated kidney weights were identified in animals exposed to low‐ or high‐dose nitrofen, but this occurred regardless of the presence of a diaphragmatic defect, suggesting that growth of the lung, heart, and kidney is directly affected by nitrofen. Because the effects of nitrofen could not be differentiated from those associated with CDDs or visceral herniation, it is impossible to resolve questions regarding the interrelationships of diaphragmatic defects and pulmonary, renal, and cardiac changes. Morphogenetic, anatomic, and other differences between laboratory rodents and humans reaffirm the need for careful extrapolation between experimental, teratogenic models and human disease. © 1993 Wiley‐Liss, Inc.
Evaluation of congenital limb reduction defects in upstate New York
Authors: Lin Shao , Marshall Elizabeth G. , Davidson Georgia K. , Roth Geraldine B. , Druschel Charlotte M. 
Published: June 2005

AbstractLimb reduction defects (LRD), reported to the Congenital Malformations Registry in upstate New York between 1983–1987, were invetigated in terms of LRD classification, parental demographics, and LRD characteristics. After excluding LRD with chromosome abnormalities, we followed guidelines developed by the European Congenital Anomaly Surveillance Consortium (EUROCAT) to classify 271 LRD into six groups based on similar patterns of embryological failure. The descriptive analysis indicated a prevalence of 0.45 per 1,000 births (stable over 5 years) for LRD diagnosed during the first 2 years of life. Among 271 LRD cases, 95 were classified as terminal transverse (35.1%), 71 as split limbs (26.2%), 36 as preaxial (13.3%), 32 as postaxial (11.8%), 26 as intercalary (9.6%), and 11 as multiple types (4.1%). In cases with multiple limb involvement (28.4%), two thirds had the same type of LRD in each limb. The multiple types and preaxial groups showed the most distinctive characteristics: they had the highest frequency of suspected syndromes, other birth defects, and syndactyly compared to the other LRD. There were no significant differences in the distribution of demographic variables among different LRD types. Consideration of the incidence and characteristics of LRD by classifying them into these distinct subgroups may be useful for evaluating possible mechanisms of malformation. © 1993 Wiley‐Liss, Inc.
Additional endpoints and overview of a mouse skeletal variant assay for detecting exposure to teratogens
Authors: Beck Sidney L. 
Published: June 2005

AbstractCD‐1 mice were exposed in utero to one of 14 treatment regimes, several of them being replicated, with close agreement between series. Prenatal exposure to a teratogenic dose at a sensitive time enabled detection of 10 of 14 teratogen regimes by alterations in frequency or severity of a substantial number of the 88 variants in the Skeletal Variant Assay System (SVAS) screen when examined at 60–65 days post natal (DPN). These included 2,4,5‐T (245T), Trifluralin (TFL), Maneb (MNB), Decamethrin (DMT), Acetazolamide (ACZM) either at 8 days post‐coitus (DPC) or days 9–11 PC, trypan blue (TB), or 5′ Bromodeoxyuridine (BUDR) on either 7 DPC, 8 DPC, or 9 DPC. Most of these observations have been reported elsewhere.All of the treatment regimes mentioned above, and another group of treatments, could be detected in the exposed CD‐1 cohorts when additional endpoints were employed. One such endpoint was “frequently responding variants.” These were: Interfrontals (IF), Parted Frontals (PF), Preoptic Sutures (PS), Foramina Transversaria Imperfecta of the first cervical (C) vertebra (FTI C1), FTI of the axis (C2), Accessory (Acc) Transverse Foramina (TF) of C3–C6, malformations of C3–C7, Fourteen (14) Ribs, Carpal Fusions (Fus), Lumbar Fus, 27‐Presacral Vertebrae (PSV), and Sacral Fus. This endpoint revealed significant differences in the initial group of 10, plus Captan (CAPT) and Phenytoin (DPH). Yet another useful endpoint reported here was the existence of high magnitude effects (i.e., dramatic alterations in frequency of occurrence of a variant). These included IF in TB and ACZM; PF in ACZM; PS in BUDR; FTI‐C1 in TB and 245T; FTI‐C2 in 245T; 14 Ribs in ACZM, BUDR, and TFL; Carpal Fus in TB; 27‐PSV in ACZM; Fewer than (<) 30 Caudal Vertebrae (Vert) in 245T, TFL; Caudal Fus in TB, ACZM‐D9. Eight treatment regimes in all could be detected by the existence of 3 or more high magnitude effects (245T, MNB, TB, ACZM8, ACZM9‐11, phenytoin, and possibly BUDR on days 7 or 8, each seen in one of two series only).Clusters of related variants were affected in 9 of the 14 groups: Frontal (F) bones and C Vert in 245T; F bones in ACZM‐D8; Fus in Posterior Vert Column in ACZM‐D9‐11; C Vert and Fus in Vert and articular skeleton in TB; Thoracic (Th) Vert and rib‐cage effects in BUDR. Finally, unique effects were seen in 4 of the 14 groups: Fused F and F Foramen (For) variants in 245T; For Palatinum Minus Posterior Double in TFL; Maxillary For I Absent (Abs), Dyssymphysis/Fus Th Vert, Tarsal Fus, the magnitude of the IF effect in TB; Acc Mental For in ACZM.Using one or more of the endpoints employed, 12 of the teratogenic regimes employed (not cortisone or thalidomide exposure) could be detected in the surviving, non‐malformed adult CD‐1 populations; 9 of the 12 were positive for three or more of the five endpoints. © 1993 Wiley‐Liss, Inc.