bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative anatomical analysis of human trisomies 13, 18, and 21: I. The forelimb
Authors: Dunlap S. S. , Aziz M. A. , Rosenbaum K. N. 
Published: June 2005

AbstractHuman trisomies 13, 18 and 21 exhibit specific neuromuscular phenotypes (Pettersen and Bersu, '82) which include a high proportion of neuromuscular forelimb variations, many of which are atavistic in nature (de Beer, '58; Barash et al., '79; Aziz, '81a). In order to test the neuromuscular phenotype, examine the atavistic nature, and analyze the developmental delay of the trisomy forearm musculature, we dissected the forelimbs of five trisomy 13, ten trisomy 18, and two trisomy 21 cases. Our dissections compare favorably with the existing published trisomy cases (Opitz et al., '79; Pettersen and Bersu, '82). Additionally, we found significant differences in the stage at which developmental arrest occurred in trisomies 13 and 18 for the pectoral complex, extensor digitorum profundus, and intrinsic hand musculature. Some of these muscles, which occur normally in nonhuman primates (Cihak, '67, '69; Dunlap et al., '85), also appear briefly in normal human ontogeny (Cihak, '72), constituting further evidence for developmental delay in aneuploids. The disproportionately effected limb tissues also lend support to the evidence for some degree of autonomy in their development in normal individuals. Our observations are consistent with Shapiro's amplified developmental instability model ('83). Aneuploids may be viewed as genetic variants from which much may be learned about normal limb development, how aneuploidy affects dysmorphogenesis, and the kind of information which exists on the duplicated (or monosomic) chromosome.
Risk factors in the prevalence of anencephalus and spina bifida in New Zealand
Authors: Barry Borman G. , Smith Allan H. , Keir Howard J. 
Published: June 2005

AbstractThis paper presents results from an epidemiological study on the 51 anencephalus and 53 spina bifida cases in the 1978 New Zealand birth cohort. Multiple sources were used in the ascertainment, and the prevalence rates were 0.98 and 1.02 per 1,000 total births, respectively. No association was found with the traditional indicators of the effect of environmental factors: maternal age, social class, nuptiality, month of birth, or estimated month of conception. Males comprised 41% of anencephalus and 36% of spina bifida cases; the prevalence was higher in the non‐Maori than in the Maori population. New Zealand‐born mothers appear to have a much lower risk of spina bifida, but not anencephaly, than those born in England/Scotland. The rate for the latter population was within the range of a number of UK‐based studies. As the bloodstock of New Zealand whites has been predominantly derived from the UK population, and as New Zealand is a low prevalence area, this suggests that the higher risk for these women is likely to be attributable to factors present in their birthplace but absent in New Zealand. These findings provide further evidence that the epidemiologic patterns of anencephalus and spina bifida in low‐prevalence areas are at variance with those in high‐prevalence areas, such as the United Kingdom. They also support the hypothesis that the contrast in rates between high‐ and low‐prevalence areas is a reflection of the impact of environmental factors in high‐prevalence areas on the “background” or baseline frequency of anencephalus and spina bifida found in low‐prevalence areas.
Maternal metabolism and teratogenesis in zinc‐deficient rats
Authors: Record I. R. , Dreosti I. E. , Tulsi R. S. , Manuel S. J. 
Published: June 2005

AbstractEmbyos removed at 11.5 days gestation from pregnant rats allowed a zinc‐deficient diet from the time of mating showed a high frequency of malformations of all organ systems. There were, however, large differences between litters of individual dams. Comparison of the daily food intake of zinc‐deficient dams with the appearance of the embryos suggested that fluctuations in the maternal serum zinc levels induced by feeding or fasting influenced the availability of zinc to the embryos. By cyclically feeding zinc‐deficient dams to a predetermined schedule, low maternal serum zinc levels were induced at selected stages of development. This was accompanied by specific malformations of the organs developing at that time.
Caffeine effects on cyclic AMP levels in the mouse embryonic limb and palate in vitro
Authors: Schreiner Claire M. , Zimmerman Ernest F. , Wee Elizabeth L. , Scott William J. 
Published: June 2005

AbstractCaffeine is a teratogen that causes limb and palate malformations in rodents. Since the ability to raise cyclic nucleotide levels is a known biological action of caffeine, cyclic AMP levels were measured in CD‐1 mouse embryonic forelimb from whole embryo culture and embryonic limb and palate cells grown in primary culture following treatment with various concentrations of caffeine (0, 1, 3, or 10 mM). In forelimb buds from whole embryo culture, a dose‐dependent response was observed. Caffeine at 1 mM concentration stimulated cyclic AMP levels to 151% of control value at 60 min. Even greater stimulation of cyclic AMP occurred at higher caffeine concentrations. A dose‐dependent response was seen in both limb and palate cell culture. In limb cell culture, all caffeine concentrations significantly stimulated cyclic AMP after 10 min compared to control. In palate cell culture, there was a twofold increase in cyclic AMP at the 1‐mM caffeine concentration. At higher caffeine concentrations, cyclic AMP was significantly increased after 60 min. In addition, stimulation of cyclic AMP in cultured limb and palate cells by isoproterenol, a beta‐adrenergic agonist, was used as a positive control. Isoproterenol stimulated a 2.5‐fold greater response in the palate cells than in the limb bud cells at isoproterenol levels of 10−5 or 10−4 M. The increase of cyclic AMP may be influential in the process of abnormal limb or palate development.
The position effect in mice on day 14
Authors: Domarus Helmut V. , Louton Tom , Lange‐Wühlisch Frank 
Published: June 2005

AbstractPrevious publications have produced conflicting results concerning the effect and nature of uterine horn position on embryonic weight and development in the uterus bicornis. For this investigation we used 503 embryos from 41 litters of NMRI ‐ mice on gestational day 14. The relative position of each embryo was determined by measuring the distance from the center of each placenta to the cervix in relation to the total length of the uterine horn. After cessation of shrinkage due to fixation the umbilical cord and remaining membranes were removed under the dissecting microscope and the embryos were weighed to the nearest 0.1 mg. Analysis of potential embryonic positions along the uterine horns indicated that 10% at the extreme ovarian and cervical ends were almost devoid of implantations. A mixed nested analysis of variance was used as the appropriate model to test a position on weight effect. Not only was a position effect found but, in contrast to other studies, it is also quantitatively represented. Embryos were lighter both at the ovarian and cervical ends, the mean weight difference being in the range of less than 10% of the average embryo weight.
Acetazolamide teratogenesis in Wistar rats: Potentiation and antagonism by adrenergic agents
Authors: Ugen Kenneth E. , Scott William J. 
Published: June 2005

AbstractAcetazolamide, a carbonic anhydrase inhibitor, induced right forelimb ectrodactyly in rat fetuses when the mothers were treated on late day 10 and early day 11 of gestation. Coadministration of the selective alpha‐1‐adrenergic agonist phenylephrine significantly increased the incidence of acetazolamide‐induced right forelimb ectrodactyly while failing to induce the lesion when administered alone. Pretreatement with the alpha‐adrenergic antagonists phenoxybenzamine and prazosin prevented the phenylephrine‐induced increase in right forelimb ectrodactyly. In addition, treatment with either phenoxybenzamine or prazosin in the absence of stimulation with phenylephrine significantly decreased the incidence of acetazolamide‐induced ectrodactyly. The results suggest an adrenergic component in acetazolamide teratogenesis. Alterations in uterine blood flow are discussed as a plausible mechanism for the modification of the incidence of ectrodactyly by these adrenergic agents.
Effect of inorganic lead on the primordial germ cells in the mouse embryo
Authors: Wide Mariann , D'argy Roland 
Published: June 2005

AbstractEmbryos from mice exposed to lead chloride (20 μg/gm body weight) by a single intravenous injection on day 8 of gestation were examined regarding the number and distribution of their primordial germ cells on 4 consecutive days of development. The cells, visulized by histochemical staining for alkaline phosphatase, showed a normal body distribution but were significantly fewer at all four stages compared with those of control embryos of corresponding age. Furthermore, the staining of the primordial germ cells was much weaker in the embryos from the lead‐treated dams than in those from control dams, suggesting that the lead had interfered with the production or activity of alkaline phosphatease. It is assumed that these effects could have contributed to the fertility reduction previously observed in female offspring of mice exposed to lead at an early stage of pregnancy.
Operant behavior in transition reflects neonatal exposure to cadmium
Authors: Newland M. Christopher , Ng Wendy W. , Baggs Raymond B. , Gentry G. David , Weiss Bernard , Miller Richard K. 
Published: June 2005

AbstractMale Long‐Evans rats were injected with 0, 1, 3, or 6 mg/kg of cadmium chloride on the first day of life. Animals free of morphological stigmata at weaning were selected for study. Tissue concentrations of cadium and operant behavior under various fixed‐ratio (FR) schedules of reinforcement were evaluated when these rats were adults. Dose‐related increases in cadmium were present in the brains, livers, and kidneys. Dose‐related differences in behavior were most evident during the transition from fixed ratio 25 (FR 25 or 25 responses/reinforcer) to FR 75. An inverted U describes the relationship between response output during the transition to FR 75 and cadmium chloride dose:response output increased at 3 mg/kg and decreased at 6 mg/kg. The rate decreases were not correlated with weight loss that appeared after some of the animals exposed to 6 mg/kg reached 60 days of age. Challenge doses of damphetamine revealed no interaction between neonatal exposure to cadmium and d‐amphetamine. The occurrence of alterations in operatnt behavior in animals that appeared normal on a number of preweaning evaluations suggests that operant behavior in transition was sensitive to subtle effects not observed with other commonly used tests. The data provide evidence for delayed effects in the adult that are due to neonatal exposure to cadmium.
Differential effects of 4‐hydroperoxycyclophosphamide on limb development in vitro
Authors: Hales Barbara F. , Jain Ranjana 
Published: June 2005

AbstractCyclophosphamide must be metabolically activated to produce malformations in limbs developing in culture; 4‐hydroperoxycyclophosphamide is an analog of the active metabolite of cyclophosphamide, that breaks down spontaneously in solution to form 4‐hydroxycyclophosphamide. To study the mechanism by which metabolites of cyclophosphamide produce limb malformations in vitro we determined the effects of exposure of cultured limb buds to 4‐hydroperoxycyclophosphamide. Fore‐ and hindlimbs were excised from ICR mice on day 12 of gestation and cultured in roller bottles for 6 days. Limbs were exposed to 4‐hydroperoxycyclophosphamide for the first 20 hours of the culture period. Addition of 10 μg/ml of 4‐hydroperoxycyclophosphamide to forelimb or to hindlimb buds in culture produced limb reduction malformations. A dramatic decrease in total limb bone area in fore‐ and hindlimbs was observed with 10 μg/ml of 4‐hydroperoxycyclophosphamide. In forelimbs, the long bone area decreased and the paw area remained constant so that the relative contribution of the long bone area to total limb bone area was decreased. In hindlimbs treated with 10 μg/ml of 4‐hydroperoxycyclophosphamide, no paw skeleton was observed. The DNA, RNA, and protein contents of the limbs were not affected by exposure to 1 μg/ml of 4‐hydroperoxycyclophosphamide, but were decreased by exposure to 10 μg/ml of this compound. Exposure to the higher concentration of 4‐hydroperoxycyclophosphamide also decreased alkaline phosphatase activity, a marker for osteogenesis, in both fore‐ and hindlimbs; in contrast, neither concentration of 4‐hydroperoxycyclophosphamide had an effect on creatine phosphokinase activity, a marker for myogenesis. Thus, the higher concentration of 4‐hydroperoxycyclophosphamide had differential effects on enzyme markers for osteogenesis and myogenesis and, in the forelimbs, on the long bones relative to the paw skeleton. The limb reduction malformations produced by exposure in vivo to cyclophosphamide may be a consequence of selective inhibition of osteogenesis.
Effects of cadmium on lactate dehydrogenase activities in mouse pre‐embryos at various stages
Authors: Yu H. S. , Chan S. T. H. 
Published: June 2005

AbstractA decline in LDH activity from four‐cell to late blastocyst was demonstrated in pre‐embryos from F1 (C57 female × A2G male) female mice. An exposure to 0.5 or 1 μg/ml cadmium did not affect the in vitro development of the four‐cell pre‐embryos and morulae or their LDH activities. At 5 or 10 μg/ml cadmium, the in vitro development of the treated pre‐embryos was affected. Although most of the treated four‐cell pre‐embryos had proceeded to compaction, they became degenerated 24 h after treatment. The LDH activity of these degenerated pre‐embryos was higher than that in the control blastocysts. We propose that cadmium may interfere with the general energy metabolism of the cells. This causes a reduced rate of LDH degradation, leading to a slower decline in LDH activity in cadmium‐treated pre‐embryos. Failure of some critical biochemical processes after cadmium treatment may ultimately lead to the subsequent degeneration of the treated pre‐embryos.
Identification of Dh/ + and Dh/Dh embryos through close linkage of Dh and peptidase‐3
Authors: Holmes Lewis B. 
Published: June 2005

AbstractThe close linkage between the genes Dominant hemimelia (Dh) and peptidase‐3 (Pep‐3) has been determined in 65 informative matings with the recombination freqency of 3.8%. Progeny testing showed that non‐penetrance does occur in Dh/+ adults. The presence of the “slow” and “fast” variants of Pep‐3 can be determined in homogenates of kidney tissue as well as in a portion of the day 10 and 11 embryos. In a litter of embryos born to an informative mating, those which are Dh/Dh, Dh/+, and +/+ can be distinguished by the presence of the Pep‐3 allele known to be in coupling with the Dh gene. This technique makes it possible to identify and to study the limb malformations and other phenotypic effects of Dh during their development and before the limb deformity is visible.
Teratogenicity of di(2‐ethylhexyl) phthalate, 2‐ethylhexanol, 2‐ethylhexanoic acid, and valproic acid, and potentiation by caffeine
Authors: Ritter E. J. , Scott W. J. , Randall J. L. , Ritter J. M. 
Published: June 2005

AbstractIt is hypothesized that the teratogen di(2‐ethylhexyl) phthalate (DEHP) acts by in vivo hydrolysis to 2‐ethylhexanol (2‐EHXO), which in turn is metabolized to 2‐ethylhexanoic acid (2‐EHXA), the proximate teratogen. Teratological studies were conducted with Wistar rats, with administration of these agents on day 12 of gestation. On an equimolar basis DEHP was least potent, 2‐EHXO was intermediate, and 2‐EXHA was the most potent of the three agents, which is consistent with the hypothesis. Similarity in the types of defects found with these agents also suggests a common mechanism, with 2‐EHXA as the proximate teratogen. All three agents were potentiated by caffeine. Valproic acid, which is an isomer of 2‐EXHA, also produced similar defects, and was approximately twice as potent as 2‐EHXA.
Search for teratogenic risks with the aid of malformation registries
Authors: Källén Bengt 
Published: June 2005

AbstractA summary is given of experiences in the use of the Swedish registries of birth defects for causal epidemiological studies. Case‐control studies and cohort studies are described and exemplified. The application of case‐control techniques to cohorts of women selected for probable or possible exposure is also described. The importance of using large‐scale registry studies in the search for common but low‐risk teratogens is stressed.
Ethyl alcohol‐induced cardiovascular malformations in the chick embryo
Authors: Fang Tzann‐Tarn , Bruyere Harold J. , Kargas Steve A. , Nishikawa Toshio , Takagi Yasuo , Gilbert Enid F. 
Published: June 2005

AbstractChick embryos incubated for 72–80 hours were exposed to various volumes (0.20–0.40 m1/egg) of 50% ethyl alcohol. Examination of embryos at day 14 of incubation showed that higher doses of ethanol decreased the survival rate of embryos compared with control embryos. Three major categories of cardiovascular malformations were observed in this study: intracardiac anomalies characterized primarily by isolated ventricular septal defect, ventricular septal defect with overriding aorta, double outlet right ventricle or common aorticopulmonary trunk; aortic arch anomalies; and subclavian artery anomalies. Frequencies of embryos with intracardiac anomalies were equal to or greater than 64.8% in the six groups exposed to ethanol. Administration of ethanol also induced high frequencies of embryos with subclavian artery anomalies (11.2–89.1%). Absence or hypoplasia of the right and/or left secondary subclavian artery was commonly associated with persistence of the corresponding primary subclavian artery. Bilateral absence and/or hypoplasia of the secondary subclavian arteries was more common than unilateral anomalies, whereas absence of the left secondary subclavian artery was more commonly observed than an absent right secondary subclavian artery. No embryos in the two control groups combined (n = 94) demonstrated aortic arch or subclavian artery anomalies.
Strain differences in phenobarbital‐induced teratogenesis in mice
Authors: Finnell Richard H. , Shields Heidi E. , Taylor Stephen M. , Chernoff Gerald F. 
Published: June 2005

AbstractAnticonvulsant drugs are widely prescribed medications known to complicate more than 11,500 pregnancies each year in the United States. Although there is no clear consensus as to the teratogenicity of all of the clinically available compounds, it appears that most anticonvulsant drugs can induce congenital abnormalities in susceptible individuals. In a study designed to examine the role of the genotype on sensitivity to phenobarbitalinduced malformations, three highly inbred mouse strains (SWV, C57BL/6J, and LM/Bc) received the drug via chronic oral administration. Phenobarbital was found to have a significant teratogenic potential in mice, resulting in skeletal, cardiac, renal, neural, and urogenital defects in a dose‐related fashion. The LM/Bc strain was most sensitive to phenobarbital, with 46.7% of the fetuses exposed to the highest maternal plasma concentrations having malformations. C57BL/6J fetuses were the most resistant strain, with only 28.6% abnormalities.
Coadministration of methylxanthines and inhibitor compounds potentiates teratogenicity in Xenopus embryos
Authors: Dawson Douglas A. , Bantle John A. 
Published: June 2005

AbstractInhibitors of DNA synthesis (hydroxyurea and cytosine arabinoside), protein synthesis (cycloheximide and emetine), and nucleic acid synthesis (5‐fluorouracil) were administered with each of three methylxanthines (caffeine, theophylline, and theobromine) to determine if teratogenic effects could be potentiated in Xenopus laevis embryos. The animals were exposed for 96 hours to methylxanthine and inhibitor concentrations that, alone, produced low percentages of malformations.Coadministration of caffeine or theophylline with each inhibitor greatly increased the incidence of malformed embryos. Similar potentiation was induced when theobromine and the protein synthesis inhibitors were tested. A lesser potentiative response was produced when theobromine and the nucleic acid synthesis inhibitor were administered together. Teratogenic potentiation did not occur when theobromine was administerd in conjunction with the DNA synthesis inhibitors. Growth reduction in the treatments proved to be the most sensitive indicator of the potentiative effects.This study had two significant findings: the teratogenicity of the protein synthesis inhibitors was greatly increased upon coadministration with each methylxanthine, even though they are typically not very teratogenic by themselves, and coadministration of the DNA synthesis inhibitors with theobromine did not result in teratogenic potentiation. Additionally, this study serves as one method of validating the frog embryo teratogenesis assay‐Xenopus (FETAX), since the results obtained concur with results from similar mammalian studies.
Enhanced susceptibility of mouse embryos heterozygous for oligosyndactyly (Os/+) to mitomycin C‐induced skeletal abnormalities
Authors: Moreno Patricia A. , Epstein Charles J. 
Published: June 2005

AbstractThe mouse mutation, oligosyndactyly (Os), results in syndactyly, muscle anomalies, and deficiency of nephrons in heterozygous animals and early embryonic lethality in homozygotes. Since the homozygous lethality results from mitotic arrest with intact spindles at the time of implantation, we have hypothesized that the heterozygous manifestations may result from impairment of cell proliferation in regions with high proliferative rates. To test this hypothesis, Os/+ and +/+ mouse embryos at 6.5 days of gestation were exposed to mitomycin C (MMC), an agent that causes a high degree of embryonic cell death which is “compensated” for by a period of rapid cell proliferation. 17.9% of MMC‐treated +/+ fetuses had fused vertebrae, a significant increase over untreated fetuses, and this frequency was further increased to 33.6% in MMC‐treated Os/+ fetuses. Saline treated Os/+ and +/+ fetuses showed the same low rate (0.3%) of vertebral fusion. These results indicate that Os/+ embryos have an increased sensitivity to the vertebral fusioninducing effect of MMC at 6.5 days of gestation, a finding compatible with the hypothesis that rapid cell proliferation may be impaired in Os/+ embryos and fetuses.
Microscopic‐anatomical changes in the chick embryo after administration of 9‐(RS)‐(2,3‐dihydroxypropyl) adenine
Authors: Jelínek R. , Doskočil M. , Holý A. 
Published: June 2005

AbstractMicroscopic‐anatomical changes were followed in embryos of white leghorn fowl 1–5 days after administration of 9‐(RS)‐2,3‐dihydroxypropyl) adenine on day 2 of incubation. The main changes involved the spinal cord, eyes, and extremities, manifesting gross structural abnormalities. Development of the limb buds appeared to be arrested at stages corresponding to the third day of incubation, with their apical ectodermal ridges frequently absent. A conspicuous feature of all the experimental embryos was a seriously damaged spinal cord. The disturbance of spinal cord development was reflected in defective formation of vertebral anlagen. Development of eye anlagen was arrested at the optic cup stage. The lens, however, developed normally. No causal relationship between the CNS abnormalities and limb damage was determined.