bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetically mediated induction of drug‐metabolizing enzymes associated with congenital defects in the mouse
Authors: Lambert George H. , Nebert Daniel W. 
Published: June 2005

AbstractVarious polycyclic aromatic compounds induce certain monooxygenase activities, including aryl hydrocarbon (benzo[a]pyrene) hydroxylase (EC 1.14.14.2), and cytochrome P1‐450 in the liver and many nonhepatic tissues of the mouse. This induction process is controlled by the Ah locus. Genetic differences that have been shown in the past to be associated with the Ah locus include an increased susceptibility to chemical carcinogenesis, mutagenicity in vitro, and drug toxicity – manifested as hepatic necrosis, aplastic anemia, or shortened survival time. Pregnant mice received a single injection of 3‐methylcholanthrene or 7,12‐dimethylbenz[a] anthracene between day 5 and day 13 of gestation, and the uterine contents were examined on day 18. Striking increases were observed in the incidence of MC‐1 and DMBA‐induced resorptions and congenital malformations in the aromatic hydrocarbon “responsive” C57BL/ 6N inbred strain, and of DMBA‐induced resorptions in the “responsive” C3H/HeN and BALB/cAnN strains – when compared with the similarly treated genetically “nonresponsive” AKR/N strain. These data suggest but do not prove that an association exists between the Ah locus and developmental toxicity, i.e., teratogenesis. Although numerous teratogenic differences among inbred mouse strains have previously reported, this study is unique in that the genetic differences in teratogenicity observed were predicted in advance on the basis of known differences among these strains in polycyclic hydrocarbon metabolism regulated by the Ah locus.
Environmental heat stress effects in the hamster
Authors: Umpierre Carmen C. , Dukelow W. Richard 
Published: June 2005

AbstractExposure of Syrian hamsters for two twenty‐minute periods at 40°C on a single day of pregnancy (ranging from day 6 to day 13) resulted in differing teratogenic effects. Maximum resorption (52.6%) was seen with treatment on day 7 whereas the highest rate of malformation (51.9%) was observed with treatment on day 9. Cranial defects predominated with treatment early in pregnancy (highest incidence on day 9) while limb defects were not observed with any treatment administered before day 9. Exencepaly occurred with treath ments on days 6 and 8, with a single case after treatment on day 10. Cleft lip and cleft palate were observed with treatment on days 9 and 10.These studies illustrate the usefulness of the Syrian hamsters in teratological studies and characterize some of effects exerted after mild heat treatment at varying stages of pregnancy.
Effects of methyl mercury on murine fetal amino acid uptake, protein synthesis and palate closure
Authors: Olson Fred C. , Massaro Edward J. 
Published: June 2005

AbstractMethylmercury (MeHg: 5 mg Hg/kg maternal body weight) in 0.13 M NaCl, 0.01 M NaH2PO4‐Na2HPO4, pH 7.4 (PBS) administered to gravid CFW mice on day 12, hour 6 (126) of gestation induced a high incidence of cleft palate in fetuses examined on days 156 (72%), 166 (62%) and 176 (40%). Palate closure (100%) in PBS control animals occurred by 1410.One day post MeHg administration, total fetal protein was decreased 22% while DNA content was unaltered. Protein was maximally decreased (28%) on 146 and, thereafter, returned toward control levels. Alterations in DNA content followed a similar pattern; but the maximal decrease (32%) occurred on 156.The rate of fetal protein synthesis was depressed 5% at 129 and between 20% to 26% from this time to 136 (end of observation). The agreement between the calculated decrease in protein synthesis (19%) and the measured decrease in protein content (22%) suggests that a reduction in protein synthesis is responsible for the decreased fetal protein content.Pacental blood flow and fetal water space, measured with 3H – H2O at 1218, were not affected by MeHg treatment. However, fetal free amino acid concentrations at 1218 were generally decreased (alanine, 23.0%; valine, 9.7%; methionine, 22. 6%; isoleucine, 12.0%; leucine, 18.2%) while uptake of the non‐metabolizable amino acid, 14C‐cycloleucine, was decreased 23%. From this, it is concluded that the growth inhibitory effects of MeHg are related, at least in part, to impaired placental/fetal transfer of amino acids.
Digital anomalies in the embryonic mouse limb cultured in the presence of excess vitamin A
Authors: Nakamura Harukazu 
Published: June 2005

AbstractForelimb buds of days 10 to 12 ICR/JCL mouse embryos were cultured on a liquid medium consisting of 90% Eagle's MEM and 10% fetal calf serum. Experimental explants were exposed to retinol (10 iu/ml) for the first 24 hours of culturing. In the control explants, chondrified metacarpals and proximal phalanges increased in number as the age of the donor limb bud increased. All treated explants cultured on the experimental medium showed abnormal development compared with the controls. Lesions caused by vitamin A shifted from proximal to distal limb segments as the age of donor limb bud increased.
The effect of high doses of retinoic acid on prenatal craniofacial development in Macaca nemestrina
Authors: Yip Janice E. , Kokich Vincent G. , Shepard Thomas H. 
Published: June 2005

AbstractEight pregnant Macaca nemestrina were administered from 7.5 to 10 mg/kg retinoic acid by mouth from day 20 to 44 of gestation. All fetuses exhibited craniofacial abnormalities. The craniofacial complex was studied in detail utilizing gross photography, silver nitrate impregnation, radiography, alizarin staining, and histologic processing. Nearly all the bones of the craniofacial complex were affected; the zygomatic bone and the mandible were most severly altered. Premature fusion of the coronal suture occurred in all the specimens, and there was a clockwise rotation of the craniofacial complex on right lateral view. In general, the bones of the affected fetus were smaller and less well developed than in the control specimen. The abnormal specimens in the present investigation resembled the Treacher‐Collins syndrome in humans, and may be the result of defective neural crest cell migration in the first and second branchial arches.
The association of spinal retroflexion with limb anomalies
Authors: Bowden Releigh A. , Stephens Trent D. , Lemire Ronald J. 
Published: June 2005

AbstractThe spectrum of conditions in which retroflexion of the spine occurs includes anencephaly, iniencephaly, and Klippel‐Feil syndrome. It was suggested by Gilmour ('41) that a continuum may exist linking the latter two entities. The present paper attempts to reopen this question by reporting two specimens which have none of the above conditions, yet have spinal retroflexion and limb malformations. Combined with other isolated case reports, they show that spinal retroflexion can arise over a variable period of time.
Cleft palate in domestic animals: Epidemiologic features
Authors: Mulvihill John J. , Mulvihill Charlotte G. , Priester William A 
Published: June 2005

AbstractAmong 331 animals with cleft palate in a veterinary clinic‐hospital population, cats, mixed breed dogs and German Shepherd Dogs had low risk for cleft palate; high rates were seen in English Bulldogs, some small purebred dogs and Charolais cattle, where cleft palate occurred as part of a syndrome of multiple malformations. Many of the epidemiologic characteristics resemble features of cleft palate in humans and suggest animal breeds suitable for exploration as animal models for use by experimental teratologists, development biologists, and clinicians.
Hypervitaminosis A and matrix alterations in maxillary explants from 16‐day rat embryos
Authors: Sauer George J. R. , Evans Carlotta A. 
Published: June 2005

AbstractHypervitaminosis A in treated pregnant rats has been shown to interfere with normal palatal closure and fusion, as demonstrated by the presence of cleft palates in offspring. The observation that palatal shelves of excess witamin A exposed fetuses are stunted and delayed in rotation suggests that vitamin A may inhibit a biochemical event crucial to the successful contact of the palatal shelves. Maxillary explants from 16 day Wistar rat embryos cultured in the presence or absence of 30 IU/ml retinyl palmitate were analyzed for DNA, glycosaminoglycan, and collagen synthesis. Maxillary explants cultured in vitamin A‐containing medium showed an inhibition in DNA, GAG, and collagen synthesis in comparison to control explants. Excess vitamin A in the culture medium of maxillary explants also resulted in a reduction of intermolecular cross‐links in collagen. The possible significance of the results in terms of cleft palate and normal secondary palate formation is discussed.
Maternal characteristics and hypospadias: A case‐control study
Authors: Polednak Anthony P. , Janerich Dwight T. 
Published: June 2005

AbstractVarious characteristics were compared among mothers of 99 singleton male live births (in Upstate New York, 1970–1974) with hypospadias and mothers of 99 singleton male live births, matched for maternal age, race, and residence. Maternal (and paternal) education, maternal height and weight, and the frequency of maternal diseases did not differ between cases and controls. Mean age at menarche was significantly later, but delayed menarche (16 years) was not more frequent, in case vs. control mothers. In the latest year during which the mother was neither pregnant nor taking oral contraceptives, menstrual cycles were significantly more often asymptomatic in case vs. control mothers, implying a higher frequency of anovulatory cycles in case mothers. This suggests the need for further studies on menstrual symptoms. Among case‐control pairs with a previous pregnancy, the first pregnancy was less likely to have resulted in a male fetus in case vs. control mothers. Maternal use of exogenous sex hormones (oral contraceptives, hormone therapy, and hormone pregnancy tests) during the index pregnancy did not differ significantly between cases and controls, but the relative risk of 3.50 for hormone pregnancy tests (seven cases vs. two controls) was noteworthy in view of the results of previous studies.
Cardiovascular malformations associated with administration of prenalterol to young chick embryos
Authors: Bruyere Harold J. , Matsuoka Rumiko , Carlsson Enar , Cheung Matthias O. , Dean Roxanne , Gilbert Enid F. 
Published: June 2005

AbstractPrenalterol (levo‐1‐[4‐hydroxyphenoxy]‐3‐isopropyl‐amino‐2‐propanol), a new stimulant of cardiac β‐adrenergic receptors in man, induces cardiovascular malformations when topically administered to 2½‐through 5½‐day chick embryos (Hamburger‐Hamilton stages 17–27). Ventricular septal defects (VSD) located in the middle portion of the conal septum and classified as the simple, punched‐out type VSD without septal malalignment were the predominant malformations observed throughout the developmental period tested. Arch malformations of the aortic circulation were also observed throughout the test interval, while anomalies of the pulmonary system were observed only at Hamburger‐Hamilton stages 17 and 26–27. At stage 25 prenalterol demonstrated an acute toxicity significantly less than (1/50–1/20) epinephrine (P = .035 at concentrations of 8–10 mM) but was relatively equipotent with epinephrine in producing cardiovascular malformations. The effective median concentrations of the two agents were comparable (0.5–1.0 mM). The spectra of malformations induced by prenalterol and epinephrine were qualitatively similar. Malformations included absence of the right and/or left third aortic arch (innominate arteries), persistent remnant of the left fourth aortic arch, and VSD. These results support a previously proposed theory by these investigators that hyperstimulation of cardiac β‐adrenergic receptors in the chick embryo produces cardiovascular malformations.
Differential response of heterozygous curly‐tail mouse embryos to vitamin A teratogenesis depending on maternal genotype
Authors: Seller Mary J. , Perkins Kathleen J. , Adinolfi Matteo 
Published: June 2005

AbstractAround 60% of mice homozygous for the curly‐tail gene have neural tube defects (NTD). F1 hybrids between curyl‐tail mice (ct) and a nongenetically predisposed A strain (A) do not have NTD. Vitamin A increases the penetrance of the ct gene at doses that hardly cause any NTD in A mice. The susceptibility to vitamin A of the F1 hybrids, derived from ct female × A male and A female × ct male crosses, was examined. Either 10, 20, or 40 mg/kg was injected into the mother on the eighth day of pregnancy. The F1 hybrids did develop NTD, and there was a dose response. The number with NTD was roughly intermediate between that found in the two pure parental crosses. However, there was a significant difference in response according to whether the ct or the A was the mother, more F1 embryos having NTD in the former situation. Also, significantly more of the female F1 hybrids had NTD when the ct was the mother than when the A was the mother, but for the males, the number with NTD was the same in both crosses. The number of intrauterine deaths of F1 hybrids, seen as resorptions in each reciprocal cross, was not intermediate but matched that of the pure parental strain of the mother involved in the hybrid cross. It is concluded that gene‐environment interaction has been demonstrated, together with both a maternal effect and a contribution of the fetal genotype in the liability to produce NTD in response to vitamin A.
Palatal slit: A new spontaneous defect of the palate of C57BL/6 mice
Authors: Kusanagi Takao 
Published: June 2005

AbstractA hitherto undescribed palatal defect, here named “palatal slit,” was observed during a teratological study of C57BL/6 fetuses. The defect, involving a failure of fusion of the premaxilla and palatal shelves, corresponds to stage 7 in normal palate closure. Adult C57BL/6 mice have been observed with the defect, so it does not represent a developmental delay that is repaired postnatally. Genetic factors of an unknown nature seem to be involved in the occurrence of palatal slit, which does not appear to be related developmentally to cleft palate. Some preliminary information on the defect is reported here.
Reduction of caffeine teratogenicity in mice by inducing maternal drug metabolism with β‐naphthoflavone
Authors: York Raymond G. , Randall Joan L. , Scott William J. 
Published: June 2005

AbstractThe effect of stimulating maternal drug metabolism on caffeine teratogenicity was investigated in C57BL/6J (cytochrome P1‐450 inducible) and AKR/J (cytochrome P1‐450 noninducible) mice. The inducing agent, β‐naphthoflavone (β‐NF) in corn oil, was administered intraperiotoneally (IP) to dams at 20 or 80 mg/kg/d on days 9 and 10 of gestation. Teratogenic injections of 175 mg/kg/d caffeine in deionized water were administered IP on days 11 and 12 of gestation. All dams were sacrificed on day 18 of gestation, and fetuses were fixed for razor blade sectioning and skeletal examination. Caffeine, without maternal metabolism stimulation, caused similar types and rates of malformations in both strains of mice. Inducing drug metabolism during pregnancy with β‐NF protected the embryos from the congenital toxicities of large injections of caffeine. Reductions in embryolethality, limb malformations, and hematoma formation were evident in the inducible strain but not in the strain incapable of being induced. A dosage of eighty mg/kg/d was more effective than 20 mg/kg/d β‐NF in decreasing malformations, suggesting that stimulation of metabolism and caffeine‐induced teratogenicity are inversely related. Rapid elimination of caffeine resulting from increasing drug metabolism with the concomitant decrease in toxicity would indicate that caffeine, and not a metabolite, is the toxicant.
Effects of hyperketonemia on mouse embryonic and fetal glucose metabolism in vitro
Authors: Horton W. E. , Sadler T. W. , Hunter E. S. 
Published: June 2005

AbstractThe ketone body β‐hydroxybutyrate (B‐OHB) has been shown to be teratogenic to early‐somite mouse embryos, although the mechanism responsible for these defects has not been determined. In an attempt to define this mechanism, the present study investigated the normal pattern of both glucose and B‐OHB utilization in the developing embryo and fetus. Furthermore, the metabolic interaction of these two substrates, i.e., the potential for B‐OHB to inhibit glycolysis, was studied. All studies compared early and late embryonic periods of development as well as fetal stages. The results show that the early embryo relies almost exclusively on glycolysis for energy metabolism and suggests that there is an increasing importance of the Krebs cycle with increasing gestational age. Similarly, the early embryo has a low capacity to metabolize B‐OHB, whereas later gestational stages display a greater rate of utilization. Finally, there appears to be no inhibition of glycolysis by B‐OHB (via so‐called “substrate interactions”) during early embryonic stages. However, the compound significantly inhibits glycolysis during later embryonic and fetal stages. These studies suggest that the teratogenicity of B‐OHB in the early embryo is not due to its effects on modulating glycolysis, although this mechanism may be operating at later periods of gestation.
The interference of naloxone hydrochloride in the teratogenic activity of opiates
Authors: Jurand A. 
Published: June 2005

AbstractDiamorphine hydrochloride, methadone hydrochloride, and the synthetic enkephalin analogue FK 33‐824 are potent teratogens for the central nervous system in mouse embryos. They induce the “neurotropic syndrome of malformations,” which is restricted to the central nervous system if administered during the critical period of neural tube closure. Pretreatment with corresponding equimolecular doses of the antagonist naloxone hydrochloride applied 30 minutes before treatment with the opiate agonists abolishes the major severe malformations, i.e., exencephaly, craniorachischisis, and brachyury, and reduces the number of cases of kinking of the spinal cord. Dilation of the fourth brain ventricle remains unaffected.It is suggested that the mechanism of interference in the teratogenicity of the opiates by naloxone hydrochloride reported here is based on competition for opiate receptors. In general, these observations are regarded as evidence that the pharmacological affinity of opiate agonists to receptors in the central nervous system is responsible for the malformations caused by them in this system.
Potentiation of acetazolamide induced ectrodactyly in wistar rats by vasoactive agents and physical clamping of the uterus
Authors: Ugen Kenneth E. , Scott William J. 
Published: June 2005

AbstractThe vasoactive agents serotonin, ergotamine, and nicotine potentiate acetazolamide induced forelimb ectrodactyly (missing digits) in Wistar rats. These vasoactive agents administered alone do not produce forelimb ectrodactyly and are not known to be inhibitors of carbonic anhydrase. Additionally, physical clamping of the uterine horns in addition to oral acetazolamide administration increases the frequency of forelimb ectrodactyly, suggesting that decreased uterine blood flow can potentiate acetazolamide teratogenesis. Since the vasoactive agents used in this study are reported to possoss uterine vasoconstrictive activity, a decrease in uterine blood flow is a plausible mechanism for the potentiative ability of these agents.
Strain differences between C57BL/6 and SWV mice in time of palate closure and induction of palatal slit and cleft palate
Authors: Kusanagi Takao 
Published: June 2005

AbstractPalatal slit, which occurs spontaneously in C57BL/6 (C57BL) mice, is increased in frequency among C57BL fetuses from dams treated with triamcinolone acetonide, but is not induced in SWV fetuses. On the other hand, C57BL is more resistant than SWV to left palate induction by triamcinolone. Using these C57BL and SWV mice, the relation of palate stage and chronological age was examined from 1 P.M. on day 14 to 9 A.M. on day 16 in untreated embryos, and the condition of the palate after triamcinolone treatment on day 12 was examined at 9 A.M. on day 16. In untreated embryos, horizontalization and fusion of the palatal shelves occurred earlier in C57BL than in SWV embryos, but fusion of the primary palate with the secondary palate occurred later. After triamcinolone treatment, the development of the palate was delayed in both C57BL and SWV embryos. These results suggest that the times of normal palate closure are related to the differences between C57BL and SWV mice in their susceptibilities to palatal slit and cleft palate induction and that triamcinolone produces palatal slit and cleft palate by delaying palate closure.
Umbilical vein variations: Review of the literature and a case report of a persistent right umbilical vein
Authors: Ricklan D. E. , Collett T. A. , Lyness S. K. 
Published: June 2005

AbstractA case of a ligamentum teres formed from an obliterated right umbilical vein is described. It passed to the right branch of the portal vein. The quadrate and left lobes of the liver were not separated by the usual fissure. Very few cases of anomalous umbilical veins or persistent right umbilical veins have been recorded. Of these, several have been recorded only in the umbilical cord, while in others the persistent right umbilical vein has been found intra‐abdominally, in an extrahepatic position, and passing directly to the right atrium or to the inferior vena cava. Its presence is generally associated with severe congenital abnormalities, in contrast with the present case. In view of the high incidence of congenital defects associated with aberrant or accessory umbilical veins, when these are detected either in the umbilical cord or in the abdomen by umbilical phlebography, it is suggested that the patient should be carefully investigated for other congenital abnormalities.
Long‐term changes in medication during pregnancy
Authors: Harjulehto Tiina , Aro Timo , Saxén Lauri 
Published: June 2005

AbstractThe Finnish Register of Congenital Malformations, established in 1963, rendered possible the study of changes in medication during pregnancy. The study consisted of 659 control mothers who had delivered a healthy child during the years 1964–1984. The data of this long‐term follow‐up study were collected by interviews at Maternal Health Care Centers after delivery and were completed by filed antenatal data. The results show a continuous decreasing trend in the usage of analgesics and tranquilizers but not in the usage of antiemetics, antibiotics, and vitamins. We believe that in Finland the publicity aimed at unnecessary medication during pregnancy has affected both the mothers and the health personnel.