bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retrospective study of the relationship between agricultural use of 2,4,5‐T and cleft palate occurrence in Arkansas
Authors: Nelson C. J. , Holson J. F. , Green H. G. , Gaylor D. W. 
Published: June 2005

AbstractThe relationship between use of the herbicide 2,4,5‐T in Arkansas and the concurrent incidence of facial clefts in children was studied retrospectively. Pertinent animal studies of the toxicity of 2,4,5‐T, and related compounds were reviewed; embryotoxic and teratogenic effects, including cleft palate, have been noted in several mammalian species.Although newspaper articles appeared linking defoliant use with increased birth anomalies in South Vietnam in 1969, human epidemiology studies have not established a causal relationship between use of 2,4,5‐T and birth defects. We felt that additional information concerning the human problem was needed to complement the experimental animal data, so we analyzed facial cleft rates and concurrent estimated use of 2,4,5‐T in Arkansas during 1948‐1974. Estimated level of exposure to 2,4,5‐T was determined by categorizing the 75 Arkansas counties into high‐, medium‐, or low‐exposure groups on the basis of their rice acreage during 6‐ or 7‐year intervals beginning in 1943. A total of 1,201 cases of cleft lip and/or cleft palate for these 32 years was detected by screening birth certificates and checking the records of the Crippled Children's Services. Facial cleft rates, presented by sex, race, time period, and exposure group, generally rose over time. No significant differences were found for any race or sex combination. We believe that the general increase seen in facial cleft incidence in the high and low‐exposure groups is attributable to better case finding rather than maternal exposure to 2,4,5‐T.
Early human pregnancy with the intrauterine contraceptive device in situ: Incidence of heteroploidy
Authors: Honoré Louis H. 
Published: June 2005

AbstractAn indirect method, based on placental morphology, was used to establish the incidence of heteroploidy in early human pregnancy and to determine the possible effect of the IUD on its occurrence. The non‐IUD‐wearing control population, comprised of 5,779 healthy fertile women undergoing therapeutic abortion for socioeconomic reasons, yielded an incidence of heteroploidy of 0.83% as compared with an overall incidence of 46.7% in our group of spontaneous aborters. In contrast heteroploidy was never detected pathologically in IUD‐associated spontaneous and therapeutic abortions. It was concluded that the IUD significantly prevented the development of heteroploid conceptuses. The biological and clinical significance of these findings was discussed.
Biochemical and electrophoretic studies of cholinesterases in the muscular dysgenesis (mdg) mutant mouse
Authors: Nawrot Peter S. , Howell William E. , Wenger Byron S. 
Published: June 2005

AbstractAcetyl‐ and butyrylcholinesterase activities were investigated in muscle, brain, blood plasma and erythrocyte membranes obtained from adult and fetal mice of different genotypes ( + / +, +/mdg, +/?, and mdg/mdg) with respect to the muscular dysgenesis (mdg) mutant gene. The study revealed that both AChE and BChE are present in muscle, brain and plasma, whereas erythrocyte membranes exhibit only AChE activity. Significantly lower (P < 0.05) AChE activity was observed in thigh muscle of 20‐day‐old fetuses homozygous for the mutant gene, compared with muscles of wild ( + / + ) and unknown genotypes ( + /?). The mutant (mdg/mdg) fetuses had a slightly significantly (P < 0.05) depressed level of AChE activity in brain tissue, as compared to fetuses of unknown genotype ( + /?). AChE activity was higher (P < 0.05) in the plasma of (mdg/mdg) fetuses than in that of fetuses of unknown genotype ( + /?) but did not differ significantly from those of wild type ( + / + ) fetuses. Samples of the same tissues were subjected to zone electrophoresis, for investigating patterns of cholinesterase isozymes, non‐specific esterases and total protein. Two distinct bands and a faster moving series of poorly resolved bands of acetylcholinesterase were found in muscle and brain of phenotypically normal fetuses. One of the main bands and the diffuse bands were absent in muscle and the diffuse bands were reduced in brain of homozygous (mdg/mdg) mutant fetuses. Except for increased Coomassie blue staining of a few bands in muscle, gels stained for AChE in other tissues, for BuChE, for alpha naphthyl esterase and for total protein showed no differences between mutant and control fetuses. No differences in any electrophoretic patterns were detected between heterozygous ( + /mdg) and homozygous wild type adults.
Development and standardization of screening methods for behavioral teratology
Authors: Buelke‐Sam Judy , Kimmel Carole A. 
Published: June 2005

AbstractBehavioral alterations have been reported following perinatal exposures to a variety of agents. If subtle effects of this type are to be detected and prevented, sensitive and appropriate measures are needed for prospective screening of new compounds. However, studies reported in the literature have used differing exposure regimens, postnatal environmental conditions and behavioral testing procedures thus making it difficult to determine which existing techniques have particular relevance to screening new drugs and chemicals. It is imperative that such techniques be identified or new ones be developed for screening purposes, as the incorporation of behavioral evaluation into regulatory guidelines and protocols is being considered seriously. Before behavioral assessment can become a meaningful aspect of a routine screening system, considerable research and development must occur. The objectives of such a behavioral screen must be defined. Procedural standardization must be included in efforts to identify those methods which: (1) yield reproducible results within and across laboratories; (2) are sensitive to alterations produced by a range of agents; (3) are predictive of effects in man; (4) are cost‐efficient. Identification of positive control agents, critical periods for testing and early indicators of behavioral dysfunction is urgently needed. The utility of pharmacologic/environmental challenges in unmasking functional abnormalities, and the possibility of multitesting interactions should be investigated. As the resources necessary to accomplish such a task are enormous, it is imperative that behavioral teratologists from academia, industry and government work together during all phases of such development. Interlaboratory cooperation in standardization, validation and interpretation of test methods and results is especially encouraged.
The evolution of teratological testing
Authors: Wilson James G. 
Published: June 2005

AbstractThe beginnings of mammalian experimental teratology in this century are briefly reviewed and it is noted that prior to 1960 a degree of sophistication in concept and technology had already been achieved. Thus, contrary to claims that teratology had its beginning with the thalidomide catastrophe, a modest but expanding activity and body of knowledge already existed before this unfortunate event.This activity and this knowledge, however, were largely confined to academic and research institute laboratories and made little impact on the agencies in medicine, government and industry which oversaw public health and safety and set policies intended to preserve them. No individual, group, or agency can rightly be blamed for not having sooner brought together the concepts and methodology needed for meaningful animal testing and the regulatory insight and experience needed intelligently to apply test data to human safety evaluation. To accomplish this liaison seems to have required the largest toxicological catastrophe yet recorded in human history.The major events leading to formulation of the first standardized guidelines are reviewed, but it is emphasized that even today the best animal testing can only provide a limited statement of probability regarding human risk vis‐à‐vis safety.
Morphological alterations in the developing fetal rat limb due to maternal injection of chlorambucil
Authors: Brummett Elaine S. , Johnson E. Marshall 
Published: June 2005

AbstractOn day 14 of pregnancy, rats were injected i.p. with 9.5 mg/kg of chlorambucil. At term, all the fetuses were stunted and had obvious skeletal malformations. From days 15‐‐20 of gestation there was a steady progression of cell death and histologic derangement in long bone formation. This began on day 15, the day following exposure to chlorambucil, with extensive cell death of chondroblasts in the long bone primordia. By day 16, dead or dying cells were located in the cartilage model and became associated with a higher than normal matrix to cell ratio. In day 17 limbs, many cells of the cartilage model were irregular in size and shape so that the normally precise cellular arrangement was lacking. On day 18, periosteal and enchondrial calcification was delayed and scanty. The fibular hemimelia observed in all drug‐treated term fetuses stained with alizarin appeared to result from lack of development of the proximal half of the cartilage model. The observed alterations, particularly bowing of the ulna, in the teratogen‐treated fetuses appeared to result primarily from specific cell death and formation of aberrant cell types but abnormal cell products may also play a role.
Prevention by Tiopronin (2‐mercaptopropionyl glycine) of methylmercuric chloride‐induced teratogenic and fetotoxic effects in mice
Authors: Fujimoto Toyoaki , Fuyuta Masatoshi , Kiyofuji Eiiti , Hirata Shuichi 
Published: June 2005

AbstractPrevious investigations (Fuyuta et al., 76, '79) have shown that a single oral administration of 25 mg/kg methylmercuric chloride (MMC) to pregnant ICR mice on day 10 of pregnancy induced cleft palate in a remarkably high incidence in fetuses. Based on these findings, the present study dealing with the prevention of cleft palate by Tiopronin, (2‐mercaptopropionyl glycine, Tp), was initiated. Twenty females in the positive control group were given 25 mg/kg MMC orally on day 10 of pregnancy and then given physiological saline intraperitoneally. Twenty females in the negative control group were given distilled water orally and then given saline intraperitoneally. Cleft palate was found in 98.1% of fetuses in the positive control group and none of them in the negative control group. Twenty females were pretreated with a single oral dose of 25 mg/kg MMC on day 10 of pregnancy and were posttreated with Tp intraperitoneally, immediately and at every 24, 48, and 72 hours after the MMC treatment. The doses of Tp were 320, 160 and 80 mg/kg/day. The incidences of cleft palate in fetuses were reduced to 1.49, 31.3 and 47.8% in the Tp‐treated groups with the doses of 320, 160 and 80 mg/kg/day, respectively. Tiopronin could effectively prevent the expected incidence of cleft palate. Other types of abnormalities as well as fetotoxicity represented by reduced fetal body weight were also effectively prevented with the Tp‐Treatment.
Threatened abortion, hormone therapy and malformed embryos
Authors: Matsunaga Ei , Shiota Kohei 
Published: June 2005

AbstractCausal relations between maternal genital bleeding, supportive hormone therapy and external malformations of the embryos were investigated with special reference to the critical period of organogenesis. This was done using morphological and obstetrical data obtained by Nishimura and his associates from 667 undamaged embryos derived from induced abortions whose mothers had genital bleeding in early pregnancy. In addition, data from 90 embryos with polydactyly and 38 with limb reductions in the Nishimura collection were used for case history studies. Evidence was presented to demonstrate that, for major malformations such as CNS anomalies, cleft lip, polydactyly and limb reductions, maternal genital bleeding was not a cause but a consequence of the conception of an abnormal embryo. No indication was revealed that exogenous female hormones currently used in Japan for preventing miscarriages could produce major malformations recognizable at the embryonic stage, including limb reductions, nor salvage the severely malformed embryos. This does not however mean to exclude the possible relationship of progestogens/estrogens intake during early pregnancy with an increased incidence at birth of certain internal and/or external malformations. It was suggested that most, if not all, of the minor anomalies observed at certain embryonic stages are kinds of normal variants without any functional impairment of embryonic development.
Down syndrome, water fluoridation, and maternal age
Authors: Erickson J. David 
Published: June 2005

AbstractIt has been claimed that there is a positive association between the frequency of Down syndrome and the fluoridation of drinking water. It has also been suggested that this association is most pronounced in young women. Recent congenital malformations data obtained from birth certificates from large U.S. cities have been analyzed. Some cities had fluoridated water supplies, while others had supplies deficient in fluoride. The rates of Down syndrome in the cities with fluoridated and in those with non‐fluoridated water supplies were comparable. In addition, there was no indication of any maternal age‐specific association.
The susceptibility of inbred strains of hamsters to cadmium‐induced embryotoxicity
Authors: Gale Thomas F. , Layton William M. 
Published: June 2005

AbstractPrior research has involved several aspects of cadmium‐induced embryotoxicity in non‐inbred hamsters, mice, and rats. This study compares the embryotoxic profile of cadmium in one non‐inbred (LVG) and five inbred (CB, LHC, LSH, MHA, PD4) strains of hamsters. A single IV dose (2 mg/kg) of cadmium sulfate was injected into pregnant hamsters early on the 8th gestation day. Fifteenth gestation day fetuses from treated, and control animals were studied for the kinds and incidence of external, internal, and skeletal malformations, as well as the frequency of resorptions. All six hamster strains developed significant resorption rates and external, internal, and skeletal abnormalities, e.g., exencephaly, microphthalmia, cleft lip, cleft palate, renal agenesis, rib fusions, etc. Significant interstrain differences were detected in only three categories of embryonic damage, i.e., resorptions, microphthalmia, and renal agenesis. The data of this study was compared with that of another study in which the same hamster strains were exposed to the metallic teratogen, lead. While the manner by which cadmium damages the mammalian embryo is unknown at this time, several possibilities are presented.
Abnormally elevated blood pressure in the trypan blue‐treated chick embryo during early morphogenesis
Authors: Rajala G. M. , Kaplan S. 
Published: June 2005

AbstractTreating chick embryos with trypan blue at 48 hours of incubation was previously shown to lead to: (1) distension of the caudal dorsal aortae to twice the normal cross‐sectional area by 12 hours posttreatment; (2) rupture of one or both of the dorsal aortae, with hemorrhage into the surrounding tissue spaces by 16 hours posttreatment; and (3) structural damage due to expanding caudal hematomas by 24 hours posttreatment. An increase in blood pressure, heart rate, cardiac output, or circulating fluids, or a selective weakening of the caudal tissues were proposed as possible causes of vessel rupture and hematoma formation. Our present experiments were designed to measure mean ventricular blood pressure (MVBP) and heart rate in treated and control embryos to determine what role these factors may have in the induction of caudal hematomas. Our major findings were: (1) Treated embryos had a significantly elevated MVBP, but no significant change in heart rate when compared to saline‐treated and unopened controls at 12–16 hours after treatment. (2) Treated embryos without hematomas had a slightly elevated MVBP and a significantly lower heart rate when compared to both control groups at 24 hours after treatment. (3) Treated embryos with hematomas had a significantly lower MVBP and heart rate when compared to the treated embryos without hematomas and both control groups at 24 hours after treatment. We conclude that the rupture of the dorsal aortae in trypan blue‐treated embryos is due, at least in part, to increased blood pressure.
Role of decreased cardiac output in isoproterenol‐induced cardiovascular teratogenesis in chick embryos
Authors: Gilbert Enid F. , Bruyere Harold J. , Ishikawa Shizen , Foulke Laura M. , Heimann Sandra R. 
Published: June 2005

AbstractStudies employing microcinematography, time‐lapse microphotography, electrocardiography, and bioelectrical impedance cardiography indicate that a decrease in cardiac output may be important in isoproterenol‐induced cardiovascular teratogenesis in the chick embryo and merits further investigation. It has been demonstrated by microcinematography that the rate of flow through embryonic chick hearts (Hamburger‐Hamilton developmental stages 24–26) treated with 7.5 × 10−4 M isoproterenol is less than that observed before or without drug administration. Bioelectrical impedance cardiograms have confirmed the above observations. Furthermore, isoproterenol induced momentary asystoles and depressed heart rates for as long as 1–2 hours. Pretreatment of embryos with practolol, a β‐1 adrenergic receptor antagonist, induced more normal cardiac performance after isoproterenol administration. Time‐lapse microphotographs demonstrated morphological alterations, indicating possible venous pressure changes in the vitelline system. Those findings are consistent with a hypothesis that practolol prevents isoproterenol‐induced acute heart failure in the embryonic chick.
Reproductive tract anomalies in mice after prenatal exposure to DES
Authors: Walker Bruce E. 
Published: June 2005

AbstractMice were injected prenatally with diethylstilbestrol (DES), using various treatment schedules to see if anomalies could be induced comparable to those seen in DES‐exposed women. Among 96 female offspring, the only tumors of the reproductive tract observed within 14 months of age were two benign tumors of the ovary. However, three other types of anomalies were identified among 20 mice in which the reproductive tract was sectioned. Adenosis occurred with a frequency of 40% in the upper half of the vagina, especially in the fornices. Large, transverse ridges of the vaginal mucosa were present in five mice. Metaplasia of the cervical squamo‐columnar junction was seen in 80% of the sectioned reproductive tracts. These anomalies are similar in morphology and frequency to those seen in women exposed prenatally to DES. Thus, an animal model has been discovered in which the developmental origin and eventual fate of these anomalies can be studied.
Effects of maternal diabetes on early embryogenesis: I. The teratogenic potential of diabetic serum
Authors: Sadler T. W. 
Published: June 2005

AbstractEffects of maternal diabetes on initial stages of organogenesis was examined by culturing early somite stage mouse embryos in the presence of diabetic serum. Serum for the cultures was prepared from rats which had been made mildly or severely diabetic by the intraperitoneal administration of 50 mg/kg or 75 mg/kg streptozotocin, respectively. Effects of this diabetic serum were age‐and dose‐related, with a higher incidence of malformations occurring among younger (2–3 vs 4–6 somite) embryos and among embryos exposed to serum from severely diabetic animals. The most commonly occuring anomaly was inhibition of neural tube closure which involved cranial (exencephaly) regions only, and was accompanied by growth inhibition in embryos exposed to severely diabetic serum. Histologically, embryos cultured in diabetic serum exhibited a wave of cell necrosis which occurred during the first 4–8 h of culture and was primarily restricted to neuroepithelial and prospective neural crest cells. However, by 24 h the neurotic debris had disappeared, even in severely malformed embryos. These abnormalities are similar to central nervous system defects described for offspring from diabetic mothers. Furthermore, the severity of diabetes produced by streptozotocin treatment promoted glucose and insulin levels comparable to those observed in diabetic patients.
A turner‐like phenotype in the aborted fetus
Authors: Poland Betty J. , Dill Fred , Paradice Barbara 
Published: June 2005

AbstractTwenty‐two fetuses with bilateral hygromata, lymphedema, and other associated anomalies are described. Two fetuses had a 45,X karyotype, five were sex chromatin‐negative. The association of specific external and internal anomalies is suggestive of the phenotype of Turner syndrome and a 45,X karyotype.
A compendium of the genetically induced congenital Malformations of the mouse
Authors: Kalter H. 
Published: June 2005

AbstractOver one‐quarter of the more than 870 known alleles in the house mouse cause congenital malformations, forming a valuable but hardly used experimental resource for the study of numerous aspects fo prenatal maldevelopment. These “teratogenes” are here extensively tabulated according to the types of malformations produced, and their various effects are listed, Introducing the tables are some general remarks including comments on variability of gene action and a breakdown of the number of the genes that are recessive and dominant.
Teratological and radiocephalometric analysis of craniofacial malformations induced with retinoic acid in rhesus monkeys (Macaca mulatta)
Authors: Hendrickx A. G. , Silverman S. , Pellegrini M. , Steffek A. J. 
Published: June 2005

AbstractFifteen pregnant Macaca mulatta were treated with doses of 20 or 40 mg of retinoic acid between 19–45 or 17–45 days of gestation, respectively, for 4–8 consecutive days. Based on gross examination, ten malformed infants, including one stillbirth and one abortus, four normal infants, and one resorption were produced. The most critical sensitive period was between days 24–35 of gestation, and the malformations primarily involved the craniofacial skeleton. Ten treated infants and eight age‐matched controls were cephalometrically analyzed using craniometric points as closely correlated as possible with those in humans in order to define the craniofacial malformations induced prenatally by retinoic acid. Although all ten animals had detectable linear and angular deviations from the controls, four had cephalometric patterns which appeared to be of similar developmental origin.