bluuebunny/crossref_metadata_2025_split huggingface dataset:
Response of early chick embryos to busulfan
Authors: Swartz William J. 
Published: June 2005

AbstractBusulfan, suspended in peanut oil, was injected into the yolk sac of white Leghorn chick embryos in dosages of 0.1 mg, 0.5 mg, or 1.0 mg. Embryos received a single injection of busulfan either prior to incubation, at 24, 48, 72, or 96 hours of incubation. Surviving embryos were sacrificed when they reached five days of incubation. Some embryos exposed to busulfan at 96 hours were allowed to develop to nine days of incubation to determine whether the time of initial exposure or the length of exposure to busulfan was more critical. The embryo required 48 hours to manifest the deleterious effects of busulfan. Abnormalities such as defects in the formation of the limb buds and cephalic hematomas were commonly seen in survivors no matter when exposed to busulfan. Some embryos injected at 96 hours and allowed to develop to nine days displayed edema of the body cavities. The role of busulfan in eliciting these malfomations is discussed.
Cell cycle phase specificity of hydroxyurea and its effects on the cell kinetics in embryonic spinal cord
Authors: Herken R. 
Published: June 2005

AbstractPregnant mice (NMRI) received an intravenous injection of 500 mg/kg of hydroxyurea (HU) on day 10 of gestation. The animals were killed 1, 1.5, 2, 2.5, 4, 6, 8 or 10 h after application of the drug and the embryos removed. Forty‐five min. prior to sacrifice, the animals were given an intraperitoneal injection of 5 μ Ci/g 3H‐thymidine (specific activity 5 Ci/mmol). From autoradiographs of the embryos the percentage of mitoses, necroses and labelled cells of the spinal cord was determined at the various time intervals. It was observed that HU inhibited DNA‐synthesis in all S‐phase cells for more than 4 hours. All cells damaged by HU did not start DNA ‐synthesis again and became necrotic. Only cells entering the S‐phase after the influence of HU could replicate their DNA in a normal manner. It is assumed that HU possibly blocks cells in the G2‐phase and in the mitosis for a certain period of time.
A glucocorticoid receptor in fetal mouse: Its relationship to cleft palate formation
Authors: Hackney John F. 
Published: June 2005

AbstractFetal mouse tissue was investigated for a glucocorticoid binding receptor which might be responsible for cleft palate formation. Fetal mouse heads contain a soluble component which binds the glucocorticoid triamcinolone acetonide in vitro with high affinity. This binding component is present in small finite amounts. Other glucocorticoids compete with triamcinolone acetonide for the binding site in a manner consistent with their potency ranking as cleft palate teratogens. Several mineralocorticoids and progestins also compete when administered in vitro but not when administered in vivo. Triamcinolone acetonide binding was determined in three mouse strains, A/J C3H, and C57BL, which are listed in decreasing order of cleft palate susceptibility to cortisone. No positive correlation was found between cortisone cleft palate susceptibility and either triamcinolone acetonide binding affinity or binding amout in fetuses from these strains. Cleft palate dose response curves for triamcinolone acetonide were determined in these strains, but they were not parallel to each other as they were for cortisone. This suggests that triamcinolone acetonide may cause cleft palate by different mechanisms in these strains. Thus, fetal mouse tissue contains and apparent glucocorticoid receptor, but its relationship to cleft palate formation in mice is not clear.
Ectopic pregnancy and myoma uteri: Teratogenic effects and maternal characteristics
Authors: Matsunaga Ei , Shiota Kohei 
Published: June 2005

AbstractMorphological data from 3,614 well‐preserved human embryos derived from artificial termination of pregnancy were used to determine whether ectopic implantation or enlarged myomas could enhance the prevalence of localized malformations of the embryo. The frequency of malformed embryos was 11.6% among 43 recovered from ectopic pregnancies, 6.2% among 97 from myomatous pregnancies, and 3.3% among 3,474 from normally implanted pregnancies not complicated by myomas. Unilateral amelia in the ectopic cases and caudal dysplasia in the myoma cases were significantly increased. Both malformations were quite unusual in the control group. It is argued that spatial restrictions could be a teratogenic agent in human embryos. Mothers of both ectopic and myoma cases were on average much older than mothers of the control specimens, and those with myomas had a higher frequency of previous pregnancy wastages. Ectopic pregnancy was found to be associated with lowered parity, previous ectopic pregnancy, and maternal smoking and drinking. These associations are discussed and interpreted in relation to etilogy of each of the two conditions.
Syndromes of cardiovascular malformations induced by copper citrate in hamsters
Authors: Dicarlo Frederick J. 
Published: June 2005

AbstractPregnant golden hamsters were injected intraperitoneally on the morning of the eighth day of gestation with a solution of copper citrate (2.7 mg/kg) or deionized water. Embryos were removed from the mothers by laparotomy on the 12th and 13th days of gestation, serially sectioned through the thorax, and examined for cardiac malformations. Twenty‐one of the 37 edematous embryos from copper‐treated mothers were affected with a total of 58 major cardiac anomalies. Sixteen of these embryos were affected with double outlet right ventricle in association with a membranous ventricular septal defect, two embryos contained hearts with overriding aortas, and three embryos were affected with isolated ventricular septal defects. Eleven of the 16 embryos with double outlet right ventricle were also affected with pulmonary trunk hypoplasia. The concept that these cardiac anomalies arise from a common pathogenetic basis is supported by the present model.
Potentiating effects of caffeine of teratogenicity of alkylating agents in mice
Authors: Fujii Takaaki , Nakatsuka Toshio 
Published: June 2005

AbstractTeratogenic to subteratogenic doses of x‐ray, mitomycin C, MNNG, thio‐TEPA, cyclophosphamide, and chlorambucil were administered to pregnant ICR mice together with caffeine at doses of 12.5, 25, or 50 mg/kg on day 11 of gestation. Fetuses were examined for gross malformations on day 18 of gestation. The teratogenicity of mitomycin C was significantly potentiated by caffeine at a dose as low as 12.5 mg/kg. The teratogenicity of chlorambucil was also significantly potentiated by caffeine at 50 mg/kg, but similar potentiation was not observed for x‐ray, MNNG, thio‐TEPA, and cyclophosphamide.
Craniofacial and central nervous system malformations induced by triamcinolone acetonide in nonhuman primates: II. Craniofacial pathogenesis
Authors: Parker R. M. , Hendrickx A. G. 
Published: June 2005

AbstractThis study further defines the craniofacial malformations induced by triamcinolone acetonide in the rhesus monkey. Ten timed‐mated pregnant rhesus monkeys (Macaca mulatta) received intramuscular injections of 10 mg/kg TAC on days 23, 25, 27, 29, and 31 of gestation. Results of previous experiments with rhesus and bonnet monkeys and baboons indicated that specific craniofacial and brain malformations could be induced with TAC during this period of pregnancy (Hendrickx et al., '80). Stage‐matched TAC‐treated and control embryos (stages 17–18 and 22) and age‐matched TAC‐treated and control fetuses (50, 60, and 70 days gestation) were removed by hysterotomy. Stage 17–18 TAC embryos appeared grossly normal but histologic evaluation revealed a shortened anlage of the posterior cranial base. Stage 22 TAC embryos and all TAC fetuses exhibited craniofacial dysmorphia and encephalocele. The developing sphenoid was the earliest affected and most severely malformed bone. Its defects included reduced anterioposterior and transverse dimensions, reduced orbitosphenoid and alisphenoid, abnormal pituitary fossa, and reduced dorsum and tuberculum sellae. In addition, shortening of the posterior cranial base and decreased cranial base angle was a consistent finding in the treated embryos and fetuses. Decreased ossification and remodeling in the facial bones and abnormal position due to the malformed sphenoid occurred.
Forebrain damage in chick embryos exposed to carbon monoxide
Authors: Daughtrey Wayne C. , Newby‐Schmidt M. B. , Norton Stata 
Published: June 2005

AbstractThe consequences of CO‐induced hypoxia to the forebrain of seven‐day‐old chick embryos were investigated. Exposure of embryos to CO for three hours caused hemorrhages in developing forebrain areas. Carboxyhemoglobin levels reached about 50% in the embryos. Two weeks later, about one day prior to hatching, morphology of large neurons in the paleostriatum primitivum was evaluated. In Golgi‐stained sections examined under the light microscope, the CO‐exposed chicks were found to have reduced branching of the dendritic tree. In addition, the nuclear size of the paleostriatum primitivum neurons was reduced in the CO‐exposed chicks. These findings in chick embryos are comparable to results in previous experiments with fetal rats.
Detection of teratogens in the Drosophila embryonic cell culture test: Assay of 100 chemicals
Authors: Bournias‐Vardiabasis Nicole , Teplitz Raymond L. , Chernoff Gerald F. , Seecof Robert L. 
Published: June 2005

AbstractAn in vitro assay of teratogenesis has been developed that utilizes Drosophila embryonic cell cultures. The endpoint selected in assessing the teratogenic potential of any substance involves detection of interference with normal muscle and/or neuron differentiation. In the validation phase of this project, 100 chemicals were tested. With drugs for which extensive reliable mammalian data are available, the results in the Drosophila assay equate rather favorably with those observed in animals and humans (i.e., a low percentage of false positives and false negatives has been obtained). In an effort to determine if strain differences exist and also to establish that the system shows a dose response, cultures from three wild‐type Drosophila strains (Canton S, Canton S109, and Oregon R) were tested. Dose‐response differences were observed when diethylstilbestrol, diphenylhydantoin, imipramine, testosterone, and tolbutamide were added to the cultures. These results suggest that the Drosophila assay, with further testing and refinements, might be capable of identifying agents of high teratogenic potential by their effect on neurons and muscle differentiation. Furthermore, sensitive strains might be used to study mechanisms of abnormal development and gene involvement in teratogenic resistance.
Ultrastructure of trypan blue induced ocular defects: I. Retina and lens
Authors: Schmidt Karmen L. , Milner Karen , Hilburn Pamela J. , Schmidt Waldemar A. 
Published: June 2005

AbstractThe histological and cytological basis of trypan blue–induced ocular defects were studied using scanning and transmission electron microscopy. Microphthalmic and anophthalmic eyes of 16‐day rat fetuses were utilized from dams exposed to a teratogenic dose of trypan blue. Retinal and lenticular anlagen were specifically examined for architectural and cellular changes. Nearly all severely abnormal eyes showed no evidence of retina development: Of 41 such eyes, only two retinal rudiments were observed. Those eyes with mild microphthalmia always demonstrated retinae although architectural changes were present. In every abnormal eye, some degree of lenticular morphogenesis was always present. Lenses were small, displaced in the eye field, and arrested at the lens vesicle stage. Lens cells were markedly undifferentiated and thus lacked most of the cytological features normally present at this developmental stage. Neither retinal nor lenticular rudiments were necrotic despite major architectural and cytological disturbances. The data offer three conclusions: First, the absence of necrosis suggests that trypan blue causes developmental arrest in this eye model; second, absence of retinae is most likely due to primary failure of optic vesicle development; third, lack of lens differentiation is attributed to absence of the retina, the primary lens inducer.
Prune perineum syndrome: Report of a second case
Authors: Williams David A. , Weiss Terry , Wade Elizabeth , Dignan Peter 
Published: June 2005

AbstractA child is reported with a constellation of anomalies which include acetabular dysplasia with bilateral dislocated hips, persistent cloaca, hypoplastic kidney, two umbilical vessels, anal atresia and no obvious external genitalia. These anomalies are strikingly similar to a case reported by Peeden et al ('79) which was referred to as prune perineum. A discussion on possible underlying cause(s) of caudal dysplasia is included.
Embryotoxic effects of doxorubicin and N‐trifluoroacetyladriamycin‐14‐valerate (AD‐32)
Authors: Zirvi Karimullah A. , Gilani Shamshad H. , Hill George J 
Published: June 2005

AbstractAnthracyclines are mutagenic, carcinogenic, and also cardiotoxic. Concern has been shown over the use of anthracycline anticancer drugs during pregnancy as these may be teratogenic to the human fetus. We have performed a series of experiments using the chick embryo to investigate and compare the toxic and teratogenic effects of doxorubicin (DX) and its new analog N‐trifluoroacetyladriamycin‐4‐valerate (AD‐32). DX and AD‐32, dissolved in 1:1 emulphor/ethanol and diluted to 1:4 with water, were injected into the air sac of white leghorn chick eggs at dose levels of 1‐20 μg (DX) and 5–100 μg (AD‐32) per egg. Eggs received a single injection of the drugs on days 1 and 2 of incubation. Control eggs were injected with an equivalent volume of the drug vehicle (0.05 ml per egg). Both of the drugs caused embryonic death, stunted growth, and various gross morphological malformations. Surviving embryos were sacrificed when they reached 13 days of incubation. The LD50 values for days 1 and 2 were as follows: (DX, 2.5 μg/egg on day 1 and 0.9 μg/egg on day 2; AD‐32, 10.6 μg/egg on day 1 and 11.8 μg/egg on day 2). Stunting of growth, a common anomaly with both drugs, decreased sharply from day 1 to day 2. The studies demonstrate that both DX and AD‐32 are toxic and teratogenic during the period of early organogenesis in the chick embryos. However, the toxic and teratogenic potentials of DX and AD‐32 differ quantitatively. AD‐32 is a more potent teratogen than DX when injected on day 1.
A comparative study of the effects or retinoic acid given during the critical period for inducing spina bifida in mice and hamsters
Authors: Tibbles L. , Wiley M. J. 
Published: June 2005

AbstractSpina bifida occurred in the offspring of golden Syrian hamsters treated on day 8 of gestation, and CD‐1 mice treated on day 9, with 80 mg/kg of retinoic acid. Light microscopic examination of term fetuses demonstrated that myeloschisis was the characteristic form of the defect in mice, whereas myelocystocele was the predominant type of spina bifida induced in the hamster. To investigate the pathogenesis of these defects, a comparative study was undertaken by light microscopy and scanning electron microscopy of the changes occurring in caudal embryonic tissues during the initial 48 hr following maternal treatment. Within 18 hr of exposure, similar effects were observed in both species. These included distortion of the neural folds at the level of the posterior neuropore, vascular damage and hematoma formation, malformation of the notochord, and abnormalities of secondary neurulation. No differences were observed that we thought could account for the apparent variation in the pattern of malformations seen in the term litters. Rather, the dissimilarity may reflect species differences in the position of the posterior neuropore in the neuraxis and in the extent to which secondary neurulation contributes to the development of the lumbosacral cord segments.
First‐trimester hemoglobin A1 and risk for major malformation and spontaneous abortion in diabetic pregnancy
Authors: Greene Michael F. , Hare John W. , Cloherty John P. , Benacerraf Beryl R. , Soeldner J. Stuart 
Published: June 2005

AbstractThe relationship between the level of hemoglobin A1 (Hb A1) in the first trimester and major malformations and spontaneous abortions was examined in 303 insulin‐requiring diabetic gravidas. During the study period, all patients with insulin‐requiring diabetes mellitus antedating pregnancy who registered for prenatal care prior to 12 weeks' gestation and who had a known outcome were included. Thirty‐five percent of the patients entered with a first‐trimester Hb A1 of greater than 11.0% of total hemoglobin (9 standard deviations above the mean for a nondiabetic population). A broad spectrum of glycemic control was therefore represented. The risk of spontaneous abortion was 12.4% with first‐trimester Hb A1 ⩽ 9.3% and 37.5% with Hb A1 > 14.4% (risk ratio 3.0; 95% confidence interval 1.3–7.0). The risk for major malformation was 3.0% with Hb A1 ⩽ 9.3% and 40% with Hb A1 > 14.4% (risk ratio 13.2; 95% confidence interval 4.3–40.4). Although the risks for both adverse outcomes were markedly elevated following a first trimester in very poor metabolic control, there was a broad range of control over which the risks were not substantially elevated. To keep malformations and spontaneous abortions to a minimum among diabetic women does not require “excellent” control; there seems to be a fairly broad range of “acceptable” control.
Transplacental estrogen responses in the fetal rat: Increased uterine weight and ornithine decarboxylase activity
Authors: Harmon James R. , Branham William S. , Sheehan Daniel M. 
Published: June 2005

AbstractThe synthetic estrogens, diethylstibestrol (DES) and ethynylestradiol (EE2), are more potent than 17β‐estradiol (E2) in inducing uterine weight gain in the neonatal rat, due to the binding of E2 to serum α‐fetoprotein (AFP). However, all three hormones are equipotent in inducing neonatal uterine ornithine decarboxylase (ODC) activity. The present study assessed estrogen potency in fetal rats. Pregnant CD rats were injected sc. daily on gestation days (GD) 16–20 with DES, EE2, or E2 in sesame oil. Both DES and EE2, but not E2, significantly increased uterine weight at birth, to more than twice that of controls. In addition, implants which continuously release E2 only slightly increased uterine weight at birth. Alternatively, dams were given a single estrogen injection on GD 20 and were sacrificed at various times after injection. Peak fetal uterine ODC activity occurred at 6–8 hours after maternal injection for all three estrogens. E2 had a relative potency about tenfold less than either DES or EE2 in stimulating fetal ODC activity, in contrast to equal potencies of the three estrogens in the postnatal rat uterus. Similar patterns were found following direct fetal injection with E2 or DES. In summary, these data demonstrate a transplacental induction of fetal uterine ODC activity and uterine weight gain by both DES and EE2. In addition, the lack of correlation between these endpoints in response to E2 suggests that they may be useful as selective indicators of potential toxicity of both natural and synthetic estrogens.
Ethylenethiourea‐induced hydrocephalus in vivo and in vitro with a note on the use of a constant gaseous atmosphere for rat embryo cultures
Authors: Khera K. S. 
Published: June 2005

AbstractEmbryos were studied either after direct exposure to ethylenethiourea (ETU) during incubation of embryo cultures or after maternal ETU dosing and subsequent embryonic development in utero with a view to assess the similarity of these two systems to produce hydrocephalus. Ten‐day‐old rat embryos were incubated with nutrient media containing 0–2.0 mM of ETU in a constant gasseous environment following a newly modified method. The cultured embryos showed hydrocephalus in the form of dilated rhombencephalon and other anomalies at the 1.5 and 2.0 mM of ETU after 26 hours of incubation. No anomalies were seen in the control group. In in vivo studies, dilated rhombencephalon or hydrocephalus was not observed when dams, orally dosed with ETU on gestation day 10, were either killed daily for three postdosing days to examine embryos or killed at term to evaluate fetuses. This discrepancy in dilatation that was incidental to the rhombencephalon in the two systems pointed out that the fourth ventricle of the cranial neural tube responded by dilatation in vitro but remained unaffected in vivo following ETU exposure. ETU dosing of dams on the 12th day of pregnancy, when embryos are known to be sensitive to ETU‐induced hydrocephalus, followed by serial gross examination of embryos, suggested that edema occurred in a generalized form but only after the appearance of both hydrocephalus (dilatation primarily in mesencephalon) and, the previously reported, neuroblastic necrosis.
Pathogenesis of persistent truncus arteriosus induced by nimustine hydrochloride in chick embryos
Authors: Miyagawa Sachiko , Kirby Margaret L. 
Published: June 2005

AbstractNimustine hydrochloride (ACNU) is a nitrosourea derivative anticancer agent which has been shown to cause persistent truncus arteriosus in chick embryos. The objective of this study was to confirm the teratogenic effects of ACNU on the cardiovascular system of chick embryos and to determine whether ACNU induces persistent truncus arteriosus by interfering with neural crest cells. Various doses of ACNU ranging from 10 to 200 μg were injected under the chorioallantoic membrane of chick embryos on the third day of incubation. Saline solution was used as the control. After 10 to 11 days of incubation, 242 (46%) survivors of the 524 treated eggs were obtained. The survival rates of the embryos and the frequencies of cardiovascular anomalies were dose dependent. Of 146 embryos with cardiovascular anomalies, 104 (71%) had persistent truncus arteriosus. Ventricular septal defect and double‐outlet right ventricle were seen in 37 (25%) and one (1%), respectively. Aortic arch anomalies were seen in 116 embryos (79%). Quail‐chick chimeras (chick embryos with quail cardiac neural crest) were treated with 50 μg of ACNU and examined histologically 24 hours later. These chimeras showed dying neural crest cells in the pharyngeal arches. Dying cells were also noted in the neural tube, cranial ganglia, retina, and otocyst. These results suggest that persistent truncus arteriosus in chick embryos treated with ACNU is induced by neural crest cell death.
Embryonic malformations in a case of intrauterine parvovirus B19 infection
Authors: Hartwig N. G. , Vermeij‐Keers C. , Van Elsacker‐Niele A. M. W. , Fleuren G. J. 
Published: June 2005

AbstractAn incomplete embryo of 9 weeks development from a woman infected by human parvovirus B19 during early pregnancy was histologically examined. B19‐DNA was detected in both embryonic and placental tissue by dot‐blot hybridization. Focal vascular endothelial damage was found throughout the entire embryo and placenta together with mononuclear infiltrations around the vessels. In the placenta these mononculear cells belonged for the greater part to the cytotoxic and/or suppressor. T‐cell group. One eye showed lens abnormalities and retinal folds. The other eye was microphthalmic and aphakic and showed dysplasia of the sclera, anterior segment, and retina. The skeletal muscle cells displayed a general eosinophilic degeneration. Focally, similar changes were found in heart muscle and smooth muscle tissue. In several tissues pathologic effects at a cellular level were noted, as intranuclear vacuole‐like inclusions and nuclear ballooning. On the basis of this study it is concluded that human parvovirus B19 may affect several fetal tissues and may even have teratological effects on a developing human embryo.