bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protective effect of deoxycytidylic acid (CdMP) on hydroxyurea‐induced malformations in rats
Authors: Chaube Shakuntala , Murphy M. Lois 
Published: June 2005

AbstractSingle ip injections of 500 mg/kg hydroxyurea (HU) to 11‐day pregnant rats produced minimal fetal mortality and malformations of the limbs, palate, jaw, and tail in 98.8% of fetuses surviving to day 21 of gestation. Simultaneous administration of 500 mg/kg HU and 700 mg/kg deoxycytidylic acid (CdMP) provided complete protection against HU teratogenesis. Lower doses of CdMP (3.7–500 mg/kg) gave partial, dose‐related, protection, as indicated by increased frequency of normal survivors and decreased severity of specific malformations. Maximal protection was provided to the forepaw and jaw and minimal to the tail. In experiments in which 700 mg/kg CdMP were given 15–60 minutes after or up to 150 minutes before HU administration, its protective effect gradually diminished with lengthening of time between the administration of the two compounds. The incidence and manifestation of individual malformations in both sets of experiments were time related. When a mixture of 700 mg/kg of CdMP and 500 mg/kg of HU was left at room temperature for 15 minutes before injection, the protective effect of CdMP was diminished by 15.1%. When the effects of several pyrimidine compounds were equated on the basis of biochemically equivalent doses (mmol/kg), among the cytidine derivatives CdMP was more effective at all doses than cytidine or deoxycytidine. All cytidine compounds gave greater protection than the uridine compounds, whereas thymidine and thymidylic acid did not protect the fetal rat against HU‐induced malformations.
Normal production of cartilage glycosaminoglycan in mice homozygous for the chondrodysplasia gene
Authors: Stephens Trent D. , Seegmiller Robert E. 
Published: June 2005

AbstractBiochemical analysis of a lethal recessive mutation affecting chondrogenesis in mice further delineated the mechanism by which this pleiotropic gene acts. Cartilage from late fetuses homozygous for chondrodysplasia (cho/cho) were terminally labeled in vitro with Na235SO4, [14C] glucosamine, and [14C] glucose. Rates of precursor incorporation; tissue contents of uronic acid, amino sugar, and protein; and molecular weight of glycosaminoglycan were determined and found normal compared with control littermate cartilage. Samples from mutants, agitated overnight in distilled water and assayed for loss of incorporated 35S, showed between 47 and 77% of control activity. The rinse water from mutant cartilage contained correspondingly more 35S than did control. Chromatographic analysis of both tissue‐bound and water‐diffusible macro‐molecules confirmed that glycosaminoglycan and protein backbone were intact. Because the molecular content and rates of precursor incorporation were normal the results suggested that the cho gene does not alter net synthesis of glycosaminoglycan. The observation that water facilitates extraction of a glycosaminoglycan‐protein complex of normal molecular weight suggests that the defect in chondrogenesis results from defective interaction of proteoglycan and some other matrix constituent. In view of a previous report that collagen fibrils of mutant cartilage are atypically large and natively banded the site of chondrogenic defect might be the interaction between proteoglycan and collagen.
Warfarin‐associated embryopathy in a 17‒week‐old abortus
Authors: Barr Mason , Burdi Alphonse R. 
Published: June 2005

AbstractHistological and anthropometric studies were made of the hands and face of a 17‐week‐old (postmenstrual) human fetus that was exposed to warfarin throughout gestation. The fetus had marked nasal hypoplasia and the facial cartilages contained discrete foci of abnormal cartilage. When compared with agematched control fetuses hand pattern profile analysis showed that the brachydactyly was due to shortening of the terminal phalanges. Histologically chondrogenesis was disordered in the carpals and phalanges, with the most deviant development occurring at the distal ends of the terminal phalanges. In none of the areas of abnormal cartilage was there evidence of hemorrhage or hemosiderin deposition. It is our contention that warfarin is teratogenic in human beings and that its teratogenicity is not due to focal hemorrhage.
Preventive effect of riboflavin and ATP on the teratogenic effects of the phenothiazine derivative T‐82
Authors: Horvath Cecilia , Szonyi Laszlo , Mold Katalin 
Published: June 2005

AbstractTo examine the hypothesis that the teratogenic effects of the phenothiazine derivative T‐82 are due to its causing a riboflavin deficiency day 11 or 12 pregnant CB Wistar rats were each given 2,000 mg/kg T‐82 po plus 100 mg/kg riboflavin ip, 12.4 mg/kg ATP ip, or both. The rates of fetal mortality and external malformations were significantly decreased in all supplementation experiments. The frequencies of cleft palate, micrognathia, and micromelia were unchanged but those of ectopic testis and hydrops fetalis were significantly increased in the group treated with T‐82 and ATP on day 12.
Growth inhibition of human embryonic and fetal rat bones in organ culture by rubella virus
Authors: Heggie Alfred D. 
Published: June 2005

AbstractPaired organ cultures of metacarpal, metatarsal, and long bones of previable human embryos, of 7 to 12 weeks' gestation, and tibias of 17‐day rat fetuses were inoculated with live or ultraviolet‐inactivated rubella virus or control fluids and the growth of the bones was measured by increase in wet weight. In several cultures the ability of the human bones to incorporate 35S, a measure of rate of mucopolysaccharide synthesis, was tested. Growth of human and rat bones was retarded in cultures inoculated with live virus but not in cultures inoculated with inactivated virus or control fluids. Mean 35S uptake was increased by approximately 25% in virus‐inoculated cultures of bones of 9‐ to 12‐week human embryos. No histological abnormalities were seen. These findings suggest that (1) defective bone growth in congenital rubella is a direct effect of viral infection of bone, (2) a disorder of mucopolysaccharide syntheses may contribute to the osseous lesions that occur in this disease, and (3) organ cultures of human embryonic and fetal rat bones may serve as convenient models for studying the pathogenesis of this virus‐induced congenital osteopathy.
Temporal, morphological, and genetic responses of avian embryos to Azodrin, an organophosphate insecticide
Authors: Schom C. B. , Abbott U. K. 
Published: June 2005

AbstractThe effect of Azodrin on avian development was studied using a bobwhite quail line and two chicken lines—a single comb White Leghorn (SCWL) and an Australorp line. The bobwhite quail embryos did not respond to injections of Azodrin until stages 22 to 23 (6 days of incubation); the SCWL embryos, not until stage 18 (3 days of incubation) with increasing susceptibility through stage 20. The threshold concentration, at stage 19, for the SCWL was 0.4 mg/kg, for the Australorp, less. Within one hour of treatment stage‐20 embryo shape was altered. There was, however, no immediate response from embryos treated earlier. The effect appeared as a reduced growth rate in the cervical flexure, and may be mediated by interference with the normal energy balance. The response, once initiated, was continuous through 10 days of incubation.
The effect of vidarabine on the development of the offspring of rats, rabbits, and monkeys
Authors: Schardein James L. , Hentz David L. , Petrere Judith A. , Fitzgerald James E. , Kurtz Stanley M. 
Published: June 2005

AbstractThe effect of vidarabine, a new antiviral agent, on the offspring of rats, rabbits, and monkeys was studied by varying routes of administration during several periods of gestation.Vidarabine demonstrated a dose‐related teratogenic effect in rats when given parenterally at doses of 30 mg/kg and greater. The drug was also teratogenic in the rabbit at dosages of 5 mg/kg and greater by the parenteral route or when applied topically in 10% concentration to 5 or 10% of the body surface area. The pattern of malformation was similar in the two species, and consisted of multiple, severe abnormalities of the head, trunk, and limbs.The drug had no demonstrable teratogenic effect in a limited study in the rhesus monkey; nor were there adverse effects on the offspring when it was applied intravaginally to pregnant rats in the perinatal period.
Craniosynostosis. II. Coronal synostosis: Its familial characteristics and associated clinical findings in 109 patients lacking bilateral polysyndactyly or syndactyly
Authors: Hunter Alasdair G. W. , Rudd Noreen L. 
Published: June 2005

AbstractThis paper is the second part of a survey of 370 patients with Craniosynostosis. It concerns 109 patients with coronal synostosis, with or without additional suture involvement who lacked polysyndactyly or syndactyly. Bilateral and unilateral coronal synostosis occurred with approximately equal frequency and there was an excess of males in both groups. Multiple suture involvements was frequent in patients with bilateral synostosis, but was uncommon in those with unilateral involvement. Those patients with bilateral synostosis and additional suture involvement were treated later than those with isolated bilateral synostosis and a possible explanation for this finding is discussed. Forty‐seven percent of patients with bilateral synostosis had additional major malformations. Cardiac malformations were significantly more frequent than would be 'expected by chance. Thirty‐five percent of patients with unilateral involvement had major malformations. Twenty‐six percent of those with bilateral and ten percent of those with unilateral synostosis were mentally retarded, but retardation was found to be associated either with increased frequency of major malformations or with a complex medical history. Mental retardation is uncommon in simple, uncomplicated coronal synostosis. Twelye of the 104 families showed a positive family history; nine with vertical and three with horizontal transmission. An admixture of unilateral and bilateral suture involvement was the rule, and families with involvement limited to unilateral synostosis did not occur. Certain patterns of characteristic familial minor malformation, particularly of the hands, allow recognition of a number of these familial cases. The recurrence risks for coronal synostosis are discussed.
The acardiac anomaly
Authors: Benirschke Kurt , Harper Virginia Des Roches 
Published: June 2005

AbstractKaryotype analysis of a premature human acardiac twin disclosed normal chromosomes. A review of previous cytogenetic, placental and animal studies suggests that chromosomal errors are not the cause of the acardiac anomaly. Rather, they point to the placental vascular anastomoses as the principal pathogenetic event.
The Klippel‐Feil Anomalad as part of the fetal alcohol syndrome
Authors: Lowry R. B. 
Published: June 2005

AbstractA brother and sister are described with malformations and handicaps consistent with both the Klippel‐Feil Anomalad and the Fetal Alcohol Syndrome. The mother was known to be a chronic alcoholic throughout both pregnancies. It is suggested that these anomalies are not purely fortuitous but rather that maternal alcoholism may cause errors in cervical vertebrae segmentation.
Alpha‐fetoprotein and albumin in experimentally‐induced exencephaly in the rat
Authors: Smith Carol J. , Kelleher Philip C. 
Published: June 2005

AbstractAlpha‐fetoprotein and albumin were quantified in the sera and amniotic fluids from control, Vitamin A‐treated non‐exencephalic and Vitamin A‐treated exencephalic rat fetuses. Exencephaly was associated with amniotic fluid alpha‐fetoprotein concentrations which were significantly elevated over those of Vitamin A‐treated non‐exencephalic and of untreated fetuses. Amniotic fluid albumin concentrations also were higher in the exencephalic fetuses than in the non‐exencephalic fetuses. Serum alpha‐fetoprotein and albumin concentrations were lower in the exencephalic than in the non‐exencephalic fetuses. The results are consistent with simple diffusion across a defective barrier as the cause of elevated amniotic fluid alpha‐fetoprotein concentrations in the presence of open neural tube defects. This experimental model of neural tube defects results in changes in amniotic fluid alpha‐fetoprotein similar to those changes found in human amniotic fluid alpha‐fetoprotein concentrations in the presence of neural tube defects.
Arsenate‐induced renal agenesis in rats,
Authors: Burk Dorothy , Beaudoin Allan R. 
Published: June 2005

AbstractThe developmental origin of arsenate‐induced renal agenesis was investigated. Pregnant Wistar rats were each injected once ip with 45 mg/kg sodium arsenate at day 10 (sperm day = day 0). Pregnancy was terminated at various times following injection and the embryos recovered and serially sectioned. Renal agenesis resulted when the mesonephric duct failed to give rise to a ureteric bud with subsequent failure of induction of the metanephric blastema. The underlying defect was retardation in growth of the mesonephric duct, first observed 48 hours after arsenate injection. A shortened mesonephric duct also resulted in a failure of the mesonephros to attain normal size and in the male resulted in absence of the ductus deferens, seminal vesicle and a variable portion of the epididymis. Due to the intimate association of the mesonephric and growing paramesonephric ducts, a shortened mesonephric duct resulted in a shortened paramesonephric duct with resultant lack of a uterine horn.
The fine structure of ventricular cells in the brains of mouse embryos homozygous for the loop‐tail gene
Authors: Wilson Doris B. 
Published: June 2005

AbstractThe neural tube in normal (+/+), heterozygous (Lp/+), and abnormal (Lp/Lp) mutant mouse embryos ranging in age from 10 to 12 days of gestation was studied by means of transmission electron microscopy. In the abnormal embryos, ventricular cells in defective regions of the brain show distortions and crowding together of internal cellular processes and a decrease in blebs and bulbous projections, as compared with their normal counterparts. At 12 days' gestation the abnormal brains show a scarcity of the T‐shaped internal cellular processes characteristic of normal brains. The abnormal brains also show increased amounts of intercellular space and extensive gaps between the cells, particularly in basal regions. There are no striking differences between the normal and abnormal brains at 10 to 12 days' gestation with respect to the appearance and distribution of cilia, microfilaments, microtubules, tight junctions, and ribosomes.
Congenital absence of the heart: Observation of human funiculopagous twinning with insertio funiculi furcata, fusion, forking, and interpositio velamentosa
Authors: Averback P. , Wiglesworth F. W. 
Published: June 2005

AbstractAn anatomic and radiologic study of a normal and acardius twinning with a single placenta is presented with literature review. The fetus was unusually well‐developed with an almost normal skeletal and brain formation, a normal genito‐urinary tract, and an absence of liver, spleen, lungs, and pancreas. The heart was absent but the great arteries, single aorta, and veins were present. The placentation is described as funiculopagous with insertio funiculi furcata, fusion, forking and interpositio velamentosa, and the latter may account for the fusion of the two circulations in this instance with the possibility that the heart was never present. The present and other observations of funiculopagous twins with two amniotic sacs suggest that the forked cord twin anomaly may occur earlier than generally recognized.
Teratogenicity of adriamycin and daunomycin in the rat and rabbit,
Authors: Thompson Daniel J. , Molello Joseph A. , Strebing Robert J. , Dyke Irene L. 
Published: June 2005

AbstractThe antitumor drugs adriamycin and daunomycin were evaluated for effects on embryonal and fetal development in the rat and rabbit. Doses of adriamycin ranging from 1‐2 mg/kg/day or daunomycin ranging from 1‐4 mg/kg/day were administered ip to pregnant rats on days 6‐15, 6‐9, 9‐12 or 12‐15 of gestation. Both drugs were teratogenic in the rat, particularly when administered on days 6‐15 or 6‐9 of gestation. Relatively few anomalies resulted from treatment on days 9‐12 or 12‐15. On a mg/kg basis, adriamycin was the more potent teratogen, producing major anomalies at doses as low as 1.25 mg/kg. Similar anomalies, but at a lower incidence, were produced by daunomycin at dose levels of 4 mg/kg. Characteristic malformations included esophageal and intestinal atresia, tracheo‐esophageal fistula, hypoplasia of the urinary bladder and various cardiovascular anomalies. Neither drug was teratogenic when given iv to rabbits at doses up to and including 0.6 mg/kg/day on days 6‐18 of gestation, but a high incidence of abortion occurred in rabbits treated with adriamycin.
Aortic aneurysm associated with cardiac defects in theophylline stimulated chick embryos
Authors: Ishikawa Shizen , Gilbert Enid F. , Bruyere Harold J. , Cheung Matthias O. 
Published: June 2005

AbstractTheophylline (1 ml 0.02 M in 0.15 M saline) was administered to embryonic chicks (Hamburger‐Hamilton developmental stages 24–27). The drug was topically applied to the surface of the chorioallantoic membrane in the vicinity of the embryonic heart.At necropsy, 63% (44/70) of the theophylline‐exposed embryos demonstrated an aneurysm in the ascending aorta.Among the cases exhibiting aortic aneurysm, 48% (21/44) of the embryos demonstrated ventricular septal defects. Four cases of truncus arteriosus were also observed.The morphogenesis and mechanism of theophylline‐induced cardiac defects with accompanying aortic aneurysm may be related to the development of the conotruncal region of the heart.
Teratogenic potential of blighted potato concentrate in rabbits, hamsters, and miniature swine
Authors: Sharma R. P. , Willhite C. C. , Wu M. T. , Salunkhe D. K. 
Published: June 2005

AbstractFreeze‐dried preparations of potatoes infected with Phytophthora infestans or Alternaria solani were fed to pregnant hamsters, rabbits, and miniature swine. No evidence was observed that these diets or the extracts of respective blights were capable of producing teratologic effects in hamsters. Lesions of neurulation and anencephaly were noticed in rabbits and swine, respectively. The need for further pharmacological and toxicological evaluation in sensitive species is emphasized.
The morphogenesis of β‐aminopropionitrile‐induced rib mal formation in fetal golden syrian hamsters
Authors: Wiley M. J. , Joneja M. G. 
Published: June 2005

AbstractIn order to provide information on the mechanism of β‐aminopropionitrile (βapn) induced teratogenesis, the pathogenesis of a fetal rib abnormality was studied at relatively short time intervals following maternal treatment with 2,500 mg/kg aqueous βapn on day 11 of gestation. Histochemical tests of ribs from βapn‐exposed fetuses indicated a slight decrease in the level of glycosaminoglycans but at a time when the defect was already morphologically established. Ultrastructural observations on the chondrocytes of ribs from βapn‐exposed fetuses revealed alterations in mitochondrial structure indicative of a slight cytotoxic effect for the teratogen. The mitochondrial changes were transient, occurring initially at three hours after treatment and lasting for nine hours. Alterations in the size of collagen fibres in the cartilage of the fetal rib were also observed in the offspring of βapn treated females. The mean diameter of collagen fibres in the ribs of control fetuses increased throughout the course of the study. The mean diameter of fibres in the fetuses of βapn‐exposed females failed to show any increase and was found to be significantly less than controls as early as three hours following maternal administration. The results suggested that the principal factor in the production of the fetal rib deformity was fundamentally the same as that known to affect the adult; namely a defect in the extracellular maturation of collagen.
Effect of 4‐methylumbelliferyl‐β‐D‐xylopyranoside on the morphology of embryonic cartilage in limb bud cultures
Authors: Merker H.‐J. , Günther Th. , Krüger U. 
Published: June 2005

AbstractLimb buds of 11‐day‐old mouse embryos were cultured for six days in the presence of 0.1, 0.5 or 2 mg/kg 4‐methylumbelliferyl‐β‐D‐xylopyranoside. A dose‐dependent decrease in chondrogenesis could be observed in preparations stained with methylene blue and cleared. A reduction or even disappearance (after 2 mg/kg) of intercellular spaces and a change in shape and size of chondroblasts was striking in the light microscopical picture. The electron microscopical findings reveal a decrease in the number, size, and electrondensity of the ruthenium‐red‐positive proteoglycan granules as well as an alteration in the collagen morphology. Up to 1,000 Å thick fibrils occur which partly show a so‐called continuous cross‐striation. In addition, bundles of thin (50–100 Å) collagen filaments without cross‐striation occur. The number, distribution and packing density of the cell organelles in the chondroblasts are very variable. The vacuoles of the Golgi apparatus are dilated. These effects may be attributed to the xyloside‐induced alterations of proteoglycans.
Toxicity of ethylenethiourea in pregnant cats
Authors: Khera K. S. , Iverson F. 
Published: June 2005

AbstractEthylenethiourea (ETU) was administered orally in single daily doses of 0, 5, 10, 30, 60 or 120 mg/kg to time‐mated cats. Daily dosing was started on day 16 of gestation in all test groups and was discontinued on the appearance of toxicity signs (between days 27–34 of gestation) in the 120 mg/kg group and on day 35 of gestation in the remaining test groups. Signs of toxicity, observed at all dose levels except in the 5 mg/kg and control, were delayed in onset and characterized by progressive loss in body weight, ataxia, tremors and hind‐limb paralysis. A number of cats died or were killed in a moribund condition in the 30, 60 and 120 mg/kg dose groups. Eleven of the thirty‐five fetuses obtained from six cats killed in a moribund state (4 from the 30 mg/kg and 1 each from the 60‐ and 120 mg/kg groups) were malformed, with coloboma occurring in four fetuses, cleft palate in two, spina bifida in one and umbilical hernia in four fetuses. Incidences of abortion and non‐pregnancy, both unrelated to the treatment, were found in all groups including the control. All surviving cats were necropsied on day 46 of gestation and fetuses were collected for teratologic evaluation. No clear evidence was found for teratogenicity of ETU in live fetuses.
Embryotoxic effects of methylmercuric chloride administered to mice and rats during organogenesis
Authors: Fuyuta Masatoshi , Fujimoto Toyoaki , Hirata Shuichi 
Published: June 2005

AbstractPregnant C57BL mice were given a daily dose of 7.5, 6.0, 5.0 or 2.5 mg/kg methylmercuric chloride (MMC) orally from the sixth through the thirteenth day of pregnancy. Pregnant Wistar rats were given a daily dose of 7.5, 5.0 or 2.5 mg/kg MMC orally from the seventh through the fourteenth day of pregnancy. Fetal examinations were performed on days 18 and 20 in mice and rats, respectively. In mice, the dose of 7.5 mg/kg was embryocidal. The dose of 6.0 mg/kg also caused a high incidence of fetal death, decreased fetal weight and a marked increase in malformations. A dose of 5.0 mg/kg caused a decrease in fetal weight and a marked increase in the incidence of malformations. The most common malformations were cleft palate and fused thoracic vertebrae. In rats, the dose of 7.5 mg/kg caused a high incidence of fetal death and malformations. The most frequent malformations were cleft palate, generalized edema, brain lesions and wavy ribs. A dose of 5.0 mg/kg caused a significant decrease in fetal weight and a significant increase in the incidence of malformations.