bluuebunny/crossref_metadata_2025_split huggingface dataset:
Teratogenic action and embryo lethality of AY 9944R: Prevention by a hypercholesterolemia‐provoking diet
Authors: Roux Charles , Horvath Cécilia , Dupuis Rolande 
Published: June 2005

AbstractEmbryomortality and teratogenesis provoked by inhibitors of cholesterol synthesis are well demonstrated. Teratogenic action is particularly reflected by holoprosencephalies, but also by uro genital abnormalities. A hypercholesterolemia‐provoking diet has been shown to be completely effective for preventing holoprosencephaly, but only partially so for preventing the urogenital malformations and fetal mortality. It is thus possible that the two types of abnormalities are governed by different mechanisms. In addition, the diet itself, whose hypercholesterolemic effect is considerable, has certain disadvantages. It seems to have a certain effect on fetal mortality and could be responsible for several uro‐genital malformations. This deserves further study.
Abnormal circulatory development in medaka caused by the insecticides carbaryl, malathion and parathion
Authors: Solomon Howard M. , Weis Judith S. 
Published: June 2005

AbstractThree insecticides, carbaryl, malathion and parathion were tested for teratogenic effects in developing medaka eggs. The concentrations of insecticides ranged from 0.5 to 40.0 parts per million (ppm). The insecticides, dissolved in acetone, were added to dishes containing 10 newly fertilized eggs and 10 ml of embryo rearing solution. Circulatory anomalies which resulted in‐cluded defects in heart morphology, pericardial edema, irregular heart beat, blood clots and oscillating blood in the heart. The ED50 (effective dose) for cabaryl was 2.5 ppm; malathion, 10.0 ppm and parathion, 2.0 ppm.Limited exposure experiments were undertaken to determine possible sensitivity periods during development. These experiments, using 10 ppm carbaryl were initiated on days 0–7. Exposure lasted 24 to 96 hours. No periods of sensitivity were observed in these experiments. In a slightly varied experiment, eggs developed normally for 0–5 days, but were not removed from the insecticide once exposed. These results showed that carbaryl could cause circulatory abnormalities in 92% of the embryos which had completed cardiac morphogenesis before exposure.Combinations of malathion and carbaryl were administered to determine possible interactions. Twenty‐five different combinations ranging from 0.0 to 25.0 ppm were employed. At low concentrations, combinations had slightly greater than additive effects. At higher concentrations additive and antagonistic effects were observed.The above experiments show that (a) these insecticides are teratogenic, (b) carbaryl at 10 ppm does not disrupt developmental events but rather affects‐cell physiology and (c) combinations of some insecticides have an additive effect.
Prevention by diazepam of adverse effects of maternal restraint stress on postnatal development and learning in the rat
Authors: Barlow S. M. , Knight A. F. , Sullivan F. M. 
Published: June 2005

AbstractRats on days 12–14 of pregnancy were treated with restraint stress alone (9h daily), restraint stress plus diazepam (1 mg/kg, twice daily), diazepam alone, or left as untreated controls. Postnatal development and behaviour was assessed on a wide‐ranging battery of tests. Offspring of mothers subjected to restraint stress alone were significantly retarded on a number of developmental measures including growth, ear‐opening, cliff avoidance response, auditory startle response and mid‐air righting reflex. When adult these offspring also showed significantly impaired learning ability in a swimming maze. However, the rate of development and learning ability in the restraint plus diazepam or diazepam alone groups was comparable to or slightly advanced of that in untreated controls. It is concluded that concurrent administration of a low dose of the tranquiliser diazepam during restraint stress prevents the adverse postnatal effects of maternal restraint stress.
Prune belly syndrome and fetal ascites
Authors: Monie Ian W. , Monie Barbara J. 
Published: June 2005

AbstractA case of prune belly syndrome (PBS) in a 22 week male fetus is described. All the features characteristic of the syndrome were present: absence of abdominal muscle; dilatation of the bladder, ureters, and renal pelves; and undescended testes. In addition, there was marked ascites. The rectus abdominis muscles were entirely absent whereas other abdominal muscles were only absent centrally. Between regions of normal and absent musculature muscle fibers were sparse, enlarged, frequently disrupted, and mostly in the myotubule stage. The prostate was thin‐walled and its urethra greatly expanded. The testes lay close to the corresponding ureters and each ductus deferens was only partially present. It is considered that prostatic dysgenesis and fetal a'scites are key factors in the causation of PBS.
In vitro metabolism of cyclophosphamide in limb bud culture
Authors: Manson Jeanne M. , Simons Ruth 
Published: June 2005

AbstractThe presence of a drug‐metabolizing system in any in vitro bioassay for teratogenicity is necessary because many chemical agents require metabolism before their activity can be expressed, and limb bud cells lack the enzymes necessary to activate these chemicals. We have taken three approaches to add a drug‐metabolizing system to limb bud culture; addition of a 9,000 × g supernatant (S9) or a purified microsomal fraction, both from mouse liver, and co‐incubation of limb buds with hamster embryo cells (HEC). The liver preparations were able to convert the teratogen cyclophosphamide to five separate metabolites with alkylating activity in limb bud culture but the cytotoxicity of these preparations limited their usefulness as metabolizing systems in limb bud culture.HEC did not exert a toxic effect on limb buds and they were able to continue metabolism of cyclophosphamide for three days. Analysis of the metabolites indicated that HEC did not convert cyclophosphamide to the same products as the liver preparations. The metabolic products were capable of inducing abnormal limb development in vitro. Addition of 14C‐cyclophosphamide in the presence of an HEC activating system led to uptake of radioactivity into limb buds. In the absence of HEC, little radioactivity was detected in the target tissue. These results suggest that culturing intact cells capable of drug metabolism with limb buds may be the most likely method to follow in achieving in vitro activation of chemicals.
Equivalent ages in rat, mouse and chick embryos
Authors: Schneider Bernard F. , Norton Stata 
Published: June 2005

AbstractData for estimating equivalent ages of rat, mouse and chick embryos are presented, using several sources from the literature. When the time of development of various embryonic structures is matched for the three species, the differences in time for the stages are primarily due to delays in development of the preimplantation blastulas of the rat and mouse in comparison with the incubated chick egg. Development from the blastula stage to completion of major organogenesis proceeds at approximately the same rate for all three species.
Unusual muscle abnormalities associated with thalidomide treatment in a rhesus monkey: A case report
Authors: Theisen Charles T. , Bodin Jeffery D. , Svoboda James A. , Pettinelli Michael W. 
Published: June 2005

AbstractUnusual musculotendinous abnormalities were observed in the forelimbs of a rhesus monkey treated prenatally with thalidomide (10 mg/kg maternal body weight, gestation days 33, 34, and 35). Although the hindlimbs exhibited malformations typical of thalidomide dysmelia, the forelimbs appeared relatively normal externally. However, dissection revealed totally anomalous insertions of preaxial muscles of both forearms. Extensor muscles inserted on flexor surfaces even though normal sites of insertion were present and unoccupied. Radiographs revealed only minor ossification deficiencies in the carpus and distal radius. These observations suggest that thalidomide, given at the appropriate time, can disrupt condensation and splitting of pre‐muscle masses without greatly disturbing condensation of corresponding pre‐skeletal elements. These types of musculoskeletal relationships are unusual findings in congenital malformations of the limbs and have not been widely associated with thalidomide teratogenesis.
Selective proliferation and accumulation of chondroprogenitor cells as the mode of action of biomechanical factors during secondary chondrogenesis
Authors: Hall B. K. 
Published: June 2005

AbstractSecondary cartilage fails to differentiate on membrane bones of embryonic chicks which have been paralyzed by the in ovo injection of Dtubocurarine chloride at ten days of incubation. A planimetric analysis of serial sections of a membrane bone (the quadratojugal) from control (mobile), and from paralyzed embryos, indicated that osteogenesis was not slowed in paralyzed embryos. However the rate of accumulation of periosteal progenitor cells was significantly lower in paralyzed than in mobile embryos. Quantitative analysis of 3H‐thymidine‐labelled progenitor cells indicated that the slowed accumulation of progenitor cells was the result of fewer progenitor cells initiating DNA synthesis and mitosis. Between 10 and 11 days of incubation, 60 to 75 more 3H‐thymidine‐labelled progenitor cells accumulated in mobile embryos than accumulated on each quadratojugal in paralyzed embryos. This subpopulation of cells could represent the chondroprogenitor cells which produce secondary cartilage in mobile embryos. If this is so, then biomechanical factors control the ability of the embryo to produce secondary cartilage by allowing the selective accumulation of chondrogenic progenitor cells.
The history of the A family of inbred mice and the biology of its congenital malformations
Authors: Kalter Harold 
Published: June 2005

AbstractThe A family of inbred mice which originated in 1921, came during its early development to have incorporated into its genome the tendency to several congenital malformations, among them cleft lip and palate. These sporadic abnormalities are of interest because they closely resemble their human counterparts in morphology and development, and because they share with them a multifactorial basis. The origins and development of the A family are traced, and the abnormalities are described and the forces affecting them detailed.
Palate morphogenesis. III. Changes in cell shape and orientation during shelf elevation
Authors: Babiarz Bruce S. , Wee Elizabeth L. , Zimmerman Ernest F. 
Published: June 2005

AbstractThe process of palate shelf elevation has been analyzed by light microscopy in mouse embryos cultured in vitro. The observations presented correlate changes in cell shape and orientation in the palate with the morphogenetic movement of the shelf. These studies suggest that in addition to any physical‐chemical force elevating the shelf an active contraction of specific palate cells could also aid the process. Contribution to elevation could be derived from masses of contracting cells from the previously described non‐muscle contractile systems in posterior (region 2) and mid‐anterior (region 3) palate as well as other peripheral mesenchymal cells. Finally, elongation and contraction of the tongue side epithelial cells may also play a role in palate elevation.
Muscular and other abnormalities in a case of Edwards' Syndrome (18‐trisomy)
Authors: Aziz M. Ashraf 
Published: June 2005

AbstractThis paper describes the anatomical variations observed in a specimen exhibiting Edwards' Syndrome (18‐trisomy). The clinical and autopsy data are compared with those reported in earlier literature. Aside from having a tracheoesophageal fistula, the viscera were characterized by abnormalities of the heart, lungs, liver and kidneys.The facial musculature was relatively undifferentiated. Only a few abnormalities were recorded in the otomandibular and suprahyoid structures. The infrahyoid region had three pairs of supernumerary muscles, including the “sternohyoideus azygos.”.The bulk of abnormalities were found in the muscles and nerves of the upper limb. These included the absence of the palmaris longus and brevis, the subclavius and the extensor digiti quinti proprius; the presence of supernumerary muscles, e.g., the “rhomboideus occipitalis,” the “latissimocondyloideus,” and the “subclavius posticus.” The deltoid and the pectoralis major were fused to form the “deltopectoral” complex. A definitive musculocutaneous nerve was found in the right arm only.In the lower extremity supernumerary muscles included the “tenuissimus,” “peroneus quinti digiti,” and the “extensor primi internodii hallucis”.
Neural tube closure defects caused by papaverine in explanted early chick embryos
Authors: Lee H. , Nagele R. G. 
Published: June 2005

AbstractPapaverine (50 μg/ml) preferentially inhibited uplifting of neural folds in explanted stage 8 chick embryos. Affected neuroepithelial cells often lost their wedge‐shaped and elongated appearance. Also, luminal surfaces of most affected cells were smoother than usual as evidenced by the marked decrease in the number of cytoplasmic extensions, but the integrity of other structures (including cytoskeletal components) was noticeably affected. The observed changes in cell surface topography were due, at least in part, to the impaired ability of apical microfilaments to contract and their eventual relaxation. The “relaxing” effect of papaverine on neural folds could be reversed by subsequent treatment with ionophore A23187. Since papaverine and ionophore A23187 are known to alter the normal distribution of intracellular Ca2+ and changes in cell surface topography are correlated with contractile activities of apical microfilaments, papaverine elicits neural tube closure defects by lowering intracellular free Ca2+ levels, thereby relaxing contracted apical microfilaments in neuroepithelial cells.
A teratogenicity study on hydroxyurea and diphenylhydantoin in cats
Authors: Khera K. S. 
Published: June 2005

AbstractHydroxyurea, an antitumor drug and known teratogen in rat, miniature swine and dog, and diphenylhydantoin, a teratogen in mouse and rat, were assessed for teratogenic effects in cat. Pregnancies were induced, by synchronizing gonadotropin‐stimulated estrus and ovulation with natural copulations. Hydroxyurea at 50 or 100 mg/kg, and sodium diphenylhydantoin at 1 or 2 mg/kg dosages, were administered orally in single daily doses from gestation days 10–22. Appropriate controls given empty capsules, were included for each drug. Cats were necropsied on gestation day 43. Fetuses were examined for external, visceral and skeletal malformations. Hydroxyurea at 50 mg/kg dose produced a low teratogenic activity and at 100 mg/kg a high incidence of non‐pregnancy and resorptions with, consequently, fewer live fetuses. Diphenylhydantoin gave no clear evidence of teratogenicity at any test dose but was embryolethal at the maternally toxic dose of 2 mg/kg. So far, studies conducted suggest that the cat is a useful species for screening drugs and chemicals for their teratogenic potential.
Teratogenic potential of phencyclidine in the mouse
Authors: Marks T. A. , Worthy W. C. , Staples R. E. 
Published: June 2005

AbstractPregnant CD‐1 mice were given phencyclidine by gavage on days 6–15 of gestation, at dose levels of 60, 80, 100, and 120 mg/kg/day. The mice were killed on day 18 and the offspring were examined for external, visceral, and skeletal alterations. There was a significant increase in the average percent of malformed fetuses per litter only at the 120 mg/kg/day dose level (6.1% versus 1.2% for the control), a dose level which resulted in the death of 8 of 18 dams before scheduled sacrifice. At dose levels less than 120 mg/kg/day, the incidence of malformations was not significantly higher than the control value, in spite of the presence of overt maternal toxicity. Because a significant number of malformations was not seen at dose levels which were not highly toxic to the dams, it was concluded that phencyclidine was not demonstrated to be a teratogen in the mouse.
Proximal 14 trisomy 46, XX, −22+der(14)t(14;22)(q21;q11)mat
Authors: Fried K. , Goldberg M. D. , Rosenblatt M. 
Published: June 2005

AbstractA firstborn newborn female was noticed to have dysplastic folded ears, odd facies, small palpebral fissures, peculiar shape of mouth and nose, clinodactily, broad chest, and short neck. Her karyotype was 46, XX, −22+der(14)t(14;22) (q21;q11)mat. Her mother was a de novo balanced reciprocal translocation carrier. The infant was the product of the rather rare adjacent 2 form of segregation. Follow‐up of the infant to the age of 19 months revealed severe mental retardation. The syndrome of proximal 14 trisomy can be suspected on clinical grounds in the newborn.
Embryo transfer in the analysis of teratological responses of mice: A critical examination
Authors: Takano Kiichi , Biddle Frederick G. , Peterson Alan C. , Miller James R. 
Published: June 2005

AbstractAlthough the technique of embryo transfer has been used extensively in preimplantation mammalian embryology, its role in experimental teratology will probably be quite. This statement is based on the authors' personal experience, a review of other studies employing the technique, and a reexamination of certain fundamental principles of teratology. The experiment reported here involved cleft palate induced by triamcinolone acetonide in the SWV (sensitive) and C57BL/10J (less sensitive) strains of inbred mice. Despite technical success in transferring embryos between the two strains, the cleft palate results were not consistent with those of the natural mating studies and were inconclusive. In contrast, fetal death due to triamcinolone was strongly nfluenced by the genotype of the famale, in both natural and embryo transfer pregnancies.
Hydrocephalus induced by N‐nitrosoethylenethiourea in the progeny of rats treated during gestation
Authors: Khera K. S. , Iverson F. 
Published: June 2005

AbstractEthylenethiourea (ETU), as result of degradation of ethylenebisdithiocarbamate fungicides, is often found in ingested foods. The interaction in vivo of ETU with the food preservative, sodium nitrite, may be expected to form N‐nitrosoethylenethiourea (NO‐ETU). To evaluate the pre‐ and postnatal effects of NO‐ETU in Wistar rats, single oral doses were administered: 120, 160, 200, and 240 mg/kg on day 13 of pregnancy in the prenatal study, and 60 and 120 mg/kg on day 15 of pregnancy in the postnatal study. In the prenatal study, the 200 and 240 mg/kg doses were maternally lethal, and the 120 and 160 mg/kg doses produced high incidences of malformed fetuses with hydrocephalus, exencephaly, hypoplastic cerebellum, hydronephrosis, and other anomalies. In the postnatal study, the 60 and 120 mg/kg doses were associated with hydrocephalus and microphthalmia.
A study of cartilaginous fusions, DNA synthesis, and protein synthesis in embryonic rat limbs after injection of aminothiadiazole
Authors: Wotring Glenn E. , Beaudoin Allan R. 
Published: June 2005

AbstractSprague‐Dawley rats were injected with 2‐amino‐1,3,4‐thiadiazole (ATDA), 100 mg/kg ip, on one of days 10–14 of pregnancy (sperm day = day 0). A supplementary ip injection of nicotinamide (N), 100 mg/kg, was administered to some rats immediately after the ATDA injection on day 12. Embryonic deaths, reduction limb malformations, and depressed fetal weights were attributable to ATDA treatment, but N coadministration was protective. Fetuses from rats dosed with ATDA or ATDA+N on day 12 were recovered on day 18 or 19 and their skeletons stained with methylene blue. Abnormal cartilaginous continuities or “fusions” between the various cartilage skeletal elements were present in 99% of limbs in the ATDA‐treated group. Extent of the fusions varied widely. In the forelimb, fusions occurred only in the carpus and paw, whereas in the hindlimb, there were many abnormal fusions of the tibia and fibula in addition to the fusions in the tarsus and paw. Cotreatment with N prevented fusions. Other rats treated on day 12 were sacrificed 4, 10, 24, 48, and 72 hours later. Embryonic limbs were cultured in vitro for two hours in a medium containing 3H‐thymidine or 14C‐leucine. Isotope incorporation was determined. Ten hours after treatment with ATDA, DNA synthesis was depressed to 1.2%–5.1% of control levels. By 72 hours, the rate of synthesis returned to normal. N coadministration was protective against the ATDA‐induced depression of DNA synthesis at 10 hours. Some changes in the rate of protein synthesis after ATDA treatment were apparent.
The effect of triamcinolone on the development of the bursa of fabricius in chick embryos
Authors: Fisher Cynthia J. , Sawyer Roger H. 
Published: June 2005

AbstractTriamcinolone acetonide (TAC), a long‐acting synthetic glucocorticoid, markedly reduces survival rates in chick embryos when injected in small (10–100 ng) single‐injection doses on days 5 or 9 of incubation. In addition to its embryotoxic effect, TAC causes such gross malformations as gastroschisis, reduced body weight, encephalocele, micrognathia, curled toes, and club feathers. These effects of TAC are more severe in 5‐day‐old chick embryos than in 9‐day‐old ones. A comparison with cortisol (hydrocortisone), a structurally similar, naturally occurring steroid, indicates that TAC is approximately 600 times more toxic in chick embryos than cortisol. TAC also inhibits differentation of the bursa of Fabricius: single injections on the chorioallantoic membrane (CAM) of 10–20 ng on day 5 or 9 reduced size and weight of this lymphoid organ. Histological examination showed a sharp reduction in the size and number of bursal follicles, a reduction in the number of lymphocytes within these follicles, and a degeneration of the epithelium covering bursal plicae.
Craniofacial and central nervous system malformations induced by triamcinolone acetonide in nonhuman primates: I. General teratogenicity
Authors: Hendrickx A. G. , Pellegrini M. , Tarara R. , Parker R. , Silverman S. , Steffek A. J. 
Published: June 2005

AbstractEighteen pregnant Macaca mulatta, 15 Macaca radiata, and six Papio cynocephalus were treated with 5–20 mg/kg triamcinolone acetonide (TAC) between 21 and 43 days of gestation on single‐ or multiple‐day treatment schedules. Prenatal deaths and stillbirths were tripled in the bonnet monkey and doubled in the rhesus monkey, but did not significantly increase in the baboon. The central nervous system and cranium were the most commonly malformed areas in all three species. The incidence of severe defects, e.g., cranium bifidum, encephalocele, meningocele, and hydrocephalus, was increased in multiple‐day treated cases. Minor abnormalities such as aplasia cutis congenita, cranium bifidum occultum, and occipital lobe hypoplasia were more prevalent in single‐day treated cases. The sensitive period (days 23–31) for TAC for this group of defects encompasses neural tube closure, rostral demarcation of the midbrain, and development of the primordial collicular plate and two midbrain neuromeres. The results of this study indicate that TAC is a valuable chemical tool for the study of malformations and pathogenesis of the brain and accompanying craniofacial defects.