bluuebunny/crossref_metadata_2025_split huggingface dataset:
The influence of D‐penicillamine on the proliferation rate of cells from the upper limb bud of mouse embryos in vitro
Authors: Herken R. 
Published: June 2005

AbstractD‐Penicillamine was given on the fourth day of culture of limb buds from 11‐day mouse embryos at a dose of 100 μg/ml medium and allowed to react for 24 hours. On day 5 there was found a significant decrease in the [3H] thymidine labeling index of cartilage cells and of cells of the perichondrium, whereas mesenchyme cells showed no decrease in proliferation under these conditions. The toxic effects of D‐penicillamine on prenatal skeletal development in vivo could therefore result not only from direct action on collagen but also via inhibition of proliferation of cartilage cells.
The fetal alcohol syndrome in mice: An animal model
Authors: Chernoff Gerald F. 
Published: June 2005

AbstractCBA and C3H female mice were maintained on liquid diets—Metrecal plus ethanol—containing 15.35% ethanol‐derived calories. These diets, which resulted in alcohol blood levels of 73.398 mg/100 ml blood in nonpregnant females, were the sole sustenance for the females for at least 30 days before and throughout gestation. Females were killed on day 18 of gestation and offspring examined for skeletal and soft tissue anomalies. Prenatal death and maldevelopment increased with the level of alcohol intake. Deficient occiput ossification, neural anomalies, and low fetal weight occurred with low ethanol diets, and cardiac and eyelid dysmorphology with higher ethanol diets. This pattern of mal‐formations, which exhibited both a dose‐response effect and strain differences in susceptibility, indicated that chronic maternal alcoholism is embryolethal and teratogenic in mice.
Ultrastructure of the expected fusion zone in rat fetuses with diazo‐oxo‐norleucine (DON)‐induced cleft palate
Authors: Morgan P. R. , Pratt R. M. 
Published: June 2005

AbstractThe aim of this study was to determine whether the glutamine analog, 6‐diazo‐5‐oxo‐L‐norleucine (DON), which is known to inhibit cell degeneration in rat palatal processes in vitro, exerted a similar effect on cleft palatal processes in vivo. Sprague‐Dawley rats were injected intraperitoneally with 5.0 mg/kg body wt of DON on Day 15 of gestation and fetuses were removed over Days 16, 17 and 18. A high frequency (80–90%) of cleft palate was obtained. Fetal heads were removed on each of the three days and transverse sections of the palatal processes were examined by light and electron microscopy. Results showed that treatment with DON failed to inhibit degenerative changes in the palatal epithelium. The same sequence and timing of ultrastructural changes occurred in the expected fusion zone (EFZ) as have been described previously in cleft palatal processes from Meclozine‐treated and amniotic sac punctured rat fetuses; namely, autophagic cytoplasmic degeneration, loss of basal lamina and the subepithelial accumulation of macrophages all of which were most prominent in that part of the EFZ immediately next to the developing oral epithelium. The results therefore suggest that a teratogenic dose of DON does not interfere with the ultrastructurally observable changes in the EFZ.
Anencephaly in trisomy 18: Related or unrelated?
Authors: Menashi M. , Ornoy A. , Cohen M. M. 
Published: June 2005

AbstractA fetus of 20 to 21 weeks of development with the trisomy 18 syndrome has been described. In addition to the phenotypic manifestations usually associated with the syndrome, i.e., low set ears, short neck, omphalocoele, flexion of fingers with the convergence of the second and fifth digits, rocker bottom feet, urinary tract anomalies and intrauterine growth retardation, the fetus also showed left diaphragmatic hernia, anencephaly and aplasia of the squamous part of occipital bone.Since anencephaly has never been described as one of the phenotypic manifestations of trisomy 18, it is reasonable to assume that in the present fetus it is unrelated and resulted from secondary destruction of the neural tube.
Cell degeneration and recovery of the fetal mammalian brain after a chemical insult
Authors: Langman Jan , Cardell Emma Lou 
Published: June 2005

AbstractIn this experiment 12‐day pregnant mice were treated with 5‐fluorodeoxyuridine, an inhibitor of DNA‐synthesis, to examine the influence of the drug on the central nervous system of the embryos. More specifically the sites of cell degeneration, the type of cells affected, and the elimination of cellular debris were investigated.Approximately two hours after treatment with FUdR, mitotic activity in the neocortex ceased and the first degenerating cells became visible in the outer zone of the neuroepithelial layer, e.g., the DNA‐synthetic zone. During the following 8 to 11 hours degenerating cells increased in number and were seen throughout the neuroepithelial layer, suggesting either that other than DNA‐synthesizing cells were affected or that degenerating cells moved from the outer zone towards the inner zone. Since all dying cells were labeled when tritiated thymidine was given shortly before FUdR treatment, it is concluded that DNA synthesizing cells have moved to the lumen despite blockage of DNA synthesis and degeneration of the nucleus. At 24 hours after treatment all degenerating cells were found in the outer region of the neuroepithelial zone, indicating that they had moved from the inner zone (near the lumen) to the outer region. Hence, the degenerating cells did not remain in the DNA‐synthetic zone, but apparently moved or were pushed from the outer to the inner zone, and vice versa.When a search was made for cells cleaning up the debris, relatively few macrophages were seen. In addition only a few normal neuroepithelial cells could be identified as containing phagocytosed material. Many degenerating cells apparently were not phagocytosed but underwent lysis, leaving temporarily large holes in the tissue. It is thus suggested that in the embryo the large amount of cellular debris is eliminated mainly by autolysis, partially by macrophages, and also to some extent by neighboring neuroepithelial cells.Despite the presence of many degenerating cells, a number of mitotic cells were seen 11 hours after treatment, indicating that the drug had ceased to act. During the following 24 hours the neuroepithelial zone is reconstituted, but few if any neuroblasts are formed. Hence, despite the extensive repair which follows the action of a chemical compound, a permanent shortage of neurons results.
T1Wh, a promising mouse strain with chromosomal markers for cleft palate research
Authors: Miller K. K. , Atnip R. L. 
Published: June 2005

AbstractAttainment of the horizontal position by the secondary palatal shelves and fusion in relationship to morphological and chronological ages in TlWh, an albino strain of mice homozygous for a 5; 19 Robertsonian translocation, was found to be late and slow in comparison to other strains previously investigated. Spontaneous and cortisone‐induced cleft palate frequencies of 3.5% and 100% respectively, were found in this strain. Its slow and late palatal closure, high susceptibility to cortisone, obvious marker chromosomes, and good breeding performance promise to make TlWh a useful strain for cleft palate research.
Differential susceptibility of the embryo to inorganic lead during periimplantation in the mouse
Authors: Wide M. , Nilsson O. 
Published: June 2005

AbstractThe effect of intravenously administered inorganic lead on periimplantation period of embryonic development in the mouse was investigated with light microscopy. Three developmental stages were studied: the attachment of the blastocyst, the invasion of the trophoblast and the formation of the primitive streak. All three stages were affected, but the stage of invasion was found to be the most susceptible to lead as determined by decrease in frequency of animals with normal embryos.
Repair mechanism in the embryonic spinal cord after a chemical insult
Authors: Crowley Karen K. , Geelen Jan A. G. , Langman Jan 
Published: June 2005

AbstractThe purpose of this experiment was to determine the level of mitotic activity of the proliferative population of the central nervous system during and after treatment with 5‐FUdR (a DNA‐synthesis inhibitor) and to examine whether the high mitotic activity seen during the repair phase was used to produce neurons or neuroepithelial cells. Chick embryos were treated with 0.01 μg 5‐fluoro‐2′‐deoxyuridine in 5 μl saline on day 2.5 of incubation and fixed at various time intervals, ranging from 1 to 120 hours after treatment.In the treated embryos the mitotic activity decreased rapidly two hours after treatment and few if any mitotic figures were seen during the following 12‐hour period. Hence, during this period few if any neuroblasts were formed. In addition, large numbers of neuroepithelial cells died as a result of the treatment, reducing the proliferative neuroepithelial population by about 50%. From 22 to 48 hours after treatment the mitotic index was almost twice that of controls, indicating that large numbers of new cells were formed to compensate for cell losses suffered during the treatment.When the number of neuroepithelial cells in the treated embryos was counted, it decreased during the first 20 hours after treatment, but thereafter increased rapidly until it reached the control value at about 50 hours after treatment. Hence, the increased mitotic activity was used mainly to increase the depleted neuroepithelial population. The neuroblast population suffered particularly, since no neuroblasts were formed during the initial degeneration phase, and only a restricted number was formed during the repair phase when the mitotic activity was used mainly for the production of neuroepithelial cells.
Congenital anomalies of the central nervous system incidence in British Columbia, 1952‐72
Authors: Trimble Benjamin K. , Baird Patricia A. 
Published: June 2005

AbstractThe records of an ongoing health surveillance registry that utilizes multiple sources of ascertainment were used to study the incidence rates of congenital malformations of the central nervous system in children born in British Columbia during the period 1952‐72. No overall increase in incidence rate of these anomalies was detected over the study period and the total frequency ascertained was three per thousand births. For anencephaly, spina bifida, hydrocephaly, and other CNS anomalies, the estimated incidence rates per 1,000 births are 0.6, 0.8, 1.0 and 0.5 respectively. A greater incidence rate of neural tube closure defects was found in females than in males and this difference was most marked amongst the stillbirths. The data indicate that multiple sources of ascertainment and follow‐up of children beyond one year after birth are necessary for adequate reporting even for these sorts of defects which have generally been thought to be readily recognized at or shortly after birth.
The craniofacial skeleton in anencephalic human fetuses. I. Cranial floor
Authors: Fields Henry W. , Metzner Louis , Garol James D. , Kokich Vincent G. 
Published: June 2005

AbstractTwelve anencephalic and four normal fetuses 26 to 40 weeks gestational age were compared by anatomic, radiographic and histologic methods in order to gain information concerning morphogenesis. In the anencephalics, alterations located within the body of the sphenoid bone led to a reduced cranial floor angle and a more vertical clivus. The reduced lateral extension of the lesser and greater wings of the sphenoid constricted the anterior and middle cranial fossae respectively. The posterior cranial fossa tended to have an increased transverse dimension related to the supraoccipital and exoccipital bone orientation. The increased anterior and inferior position of the lateral end of the petrous temporal ridge was positively correlated with the degree of dorsal schisis in the anencephalics. Alterations in the size, form, or duration of the neural functional matrix are suggested as the cause of changes in the cranial floor.
Effect of inorganic lead on the mouse blastocyst in vitro
Authors: Wide Mariann 
Published: June 2005

AbstractIn vitro culture of mouse blastocysts over the implantation period was used (1) to find out whether embryos recovered from uteri of mice given an injection of lead, which has been shown in a previous study to inhibit implantation in vivo, were capable of attachment and outgrowth when transferred to a lead free culture medium; (2) to study the effect of different amounts of inorganic lead in the culture medium on blastocyst viability and ability to attach and grow out. The levels of lead used in the medium were comparable to those found in uterine tissue of animals given an implantation inhibiting dose of lead. It was found that the preimplantation blastocyst was unaffected by the administration of lead to the mother as regards the ability to attach and grow out. It was also shown that normal blastocysts were adversely affected by the presence of lead in the culture medium. Addition of increasing amounts of inorganic lead (5, 10 and 20 μmol/l) caused a corresponding decrease in the ability of the blastocysts to attach and grow out, the highest concentration also causing abnormal appearance of the embryos within 48 hours of culture.
Hemorrhagic necrosis of the central nervous system of fetal hamsters: Litter incidence and age‐related pathological changes
Authors: Young Stuart , Keeler Richard F. 
Published: June 2005

AbstractThe occurrence, anatomic distribution, and character of lesions of spontaneous hemorrhagic necrosis (SHN) are reported in each hamster fetus of/two affected litters examined on the fifteenth day of gestation and in selected individuals of other affected litters on the twelfth, thirteenth, and fourteenth days of gestation. The pathologic process seems primarily to affect the capillary vasculature of the central nervous system and shows a predilection for rapidly growing and differentiating regions of the fetal forebrain, thalamus, and brain stem. Lesions demonstrable in members of affected litters of susceptible stocks are of a progressive character, increasing both in severity and topographic extent with increasing fetal age and growth. Spontaneous patterns of regression and recurrence of SHN disease in susceptible stocks may reflect variable physiologic factors in the intrauterine environment.
Congenital deformities produced in hamsters by potato sprouts
Authors: Keeler Richard F. , Young Stuart , Brown Dennis , Stallknecht Gilbert F. , Douglas Dexter 
Published: June 2005

AbstractDried ground potato sprout preparations from seven varieties produced congenital deformities in one strain of hamsters. Incidence of affected litters varied from 8 to 25%, depending on potato variety. Certain steroidal solanum and veratrum alkaloids produced similar defects. Neither peel nor tuber material was teratogenic from one of the potato varieties with highly teratogenic sprouts.
Effects of salicylamide and protein restriction on the skeletal development of the rat fetus
Authors: Knight Enid , Roe Daphne A. 
Published: June 2005

AbstractSalicylamide has previously been shown to be teratogenic to the rat. Aims of the present study were to examine separate effects and interactions of salicylamide administration and protein restriction on development of the rat fetus. In experiments using Holtzman rats, the percentage of fetal resorptions was significantly increased by drug treatment and by protein restriction. Malformations were seen in fetuses from dams given the drug from the fifth to eleventh days of gestation; the incidence of these malformations being independent of the diet. Factors affecting appearance of ossification centers included drug dosage, placental and fetal weight and litter size. Protein restriction had no significant effect on the development of centers of ossification.It is concluded that salicylamide, as well as protein restriction, produces adverse effects on pregnancy outcome in the rat.
Limb development in mouse embryos. II. Reduction defects, cytotoxicity and inhibition of DNA synthesis produced by cytosine arabinoside
Authors: Kochhar D. M. , Penner John D. , McDay Jane A. 
Published: June 2005

AbstractVarious morphological and biochemical parameters were used to study the mode of interference by cytosine arabinoside (Ara‐C) in critical phases of embryonic limb development. Inhibition of embryonic DNA synthesis occurred immediately after injection of Ara‐C into the mother. The inhibition was dose‐dependent and was substantial even after the nonteratogenic dose (2 mg/kg) of Ara‐C. The pattern of limb bone deficiencies in Ara‐C treated fetuses was specific for each developmental stage at which the treatment was given; the site of affect moved distalwards along the limb as the development advanced. The teratogenic dose was cytotoxic to mesenchymal cells with a high proliferation rate but did not affect others such as the future cartilage cells in which the rate of proliferation was lower. The existence of this differential susceptibility at each stage of development, together with information about the pattern of bone defects at the same stage, permitted us not only to define with some precision the cellular basis of origin of limb defects but also to infer the relative level of cell differentiation pertaining to each successive stage.Deoxycytidine, if injected simultaneously with and at doses eight times larger than Ara‐C, afforded virtually complete protection against teratogenic effects. Deoxycytidine also prevented cell death in the limbs of Ara‐C treated embryos. However, a dramatic increase in the frequency of polydactyly was found in the protected fetuses. The fact that the frequency of ectrodactyly in the protected fetuses decreased in inverse proportion to the frequency of polydactyly strengthened the notion that there may be a common cellular basis underlying these two types of digital defects.Striking changes were found in the structure of AER at 24 hours after Ara‐C treatment; it was abnormally thickened into a gland‐like structure and its inner edge facing the mesenchyme was thrown into several folds. This may constitute a response to impairment in the underlying mesenchyme with which AER has long been considered to have an interdependent relationship.
Investigation of the effect of hydroxyurea on the cell cycle and the development of necrosis in the embryonic CNS of mice
Authors: Herken R. , Merker H.‐J. , Krowke R. 
Published: June 2005

AbstractOn day 10 of gestation pregnant mice (strain NMRI) were given an intravenous injection of 500 mg/kg Hydroxyurea (HU). Simultaneously either 5 μCi/g or 10 μCi/g 3H‐thymidine (3H‐Tdr; specific activity 5 Ci/mmol) was administered to the animals. At various times after treatment embryos were removed, sectioned and prepared for autoradiography, light microscopy and electron microscopy. Two hours after administration of HU condensations of the chromatin structure could be detected electron microscopically in some cells. Thirty minutes later the nucleolus became smaller and denser, the cytoplasm shrank, and the cell organelles moved closer together. Three hours after application of the drug break‐down of the involved cells set in. As in the autora‐diograms about 98% of the counted necroses were labelled, and since labelled thymidine is almost exclusively incorporated during the S‐phase, it can be stated that HU influences only metabolic processes which take place during the S‐phase. From the morphological findings it can be concluded that in the case of the S‐phase‐specific metabolic pathway, which is influenced by HU, we are primarily dealing with DNA synthesis.
Biochemical aspects of the interactions of the teratogens 5‐fluorouracil and 5‐fluorodeoxyuridine with normal nucleic acid precursors in mice selected for low and high expression of Strong's luxoid gene
Authors: Forsthoefel Paulinus F. , Blend Michael J. , Snow June W. 
Published: June 2005

AbstractPregnant female mice selected for plus‐ and minus‐modifying genes of the limb‐skeleton effects of Strong's luxoid gene (1st) were injected ip on day 10 of gestation with 20 mg/kg of 14C‐labeled 5‐fluorouracil (FU) or 5‐fluorodeoxyuridine (FUdR) with or without added equimolecular amounts of unlabeled uracil (U) or thymidine (TD). At 1, 2, or 4 hours after injections, the treated mice were killed and their plasma, livers, embryos, and extraembryonic tissues removed. TCA‐soluble, RNA, DNA, and protein fractions were separated from the tissue samples and the radioactivity of each fraction determined.Label was incorporated into the RNA of all materials but only into the DNA of embryos. The addition of U to FU and of TD to FUdR increased the retention of FU in the TCA‐soluble fraction and the incorporation of FU into RNA. The radioactivity of the TCA‐soluble fraction declined rapidly over the entire 4‐hour sampling period, while the level of incorporation of FU into RNA of embryos and extraembryonic tissues showed large increases. No effects of 1st or of its modifiers on the biochemical parameters investigated were found.These results provide some understanding of the biochemical pathways for the teratogenicity of FU and FUdR and the effects of added U and TD.
The effect of hypervitaminosis A on rat palatal development
Authors: Lorente Carol A. , Miller Sanford A. 
Published: June 2005

AbstractRetinoic acid or retinyl acetate was administered to pregnant rats in doses sufficient to induce a 90% incidence of cleft palate. In another study, a delay in the reorientation of the palatal shelves was observed to be longer with the more potent teratogen, retinoic acid. On day 16 of gestation, 24 hours after final dosage with vitamin A, the synthesis of DNA and protein was studied in fetal carcass, mandible, and palate, and that of sulfated mucopolysaccharides (S‐MPS) and glycoproteins (GP) in fetal head, mandible, and palate. Increases in DNA synthesis in fetal palate and in GP synthesis in fetal palate were found; thus, the mechanism of action of vitamin A in inducing cleft palates in rats may be caused by interference with the normal biochemical synthetic pattern of the palatal shelves.
Teratogenic potential of ethanol in mice, rats and rabbits
Authors: Schwetz B. A. , Smith F. A. , Staples R. E. 
Published: June 2005

AbstractPregnant CF‐1 mice, Sprague‐Dawley rats and New Zealand white rabbits were given 15% ethanol in their drinking water during the period of major organogenesis, from day 6 through 15 of gestation in mice and rats and days 6 through 18 of gestation in rabbits. Maximum blood alcohol levels, measured in non‐pregnant animals, were about 200 mg percent in mice and 25–50 mg percent in rats and rabbits. Maternal toxicity in the form of decreased liquid intake and decreased maternal body weight occurred in all species during the experimental period. A significant increase in the incidence of external or soft tissue alterations was not observed in the alcohol‐exposed groups of any species, but a significant increase in minor skeletal variants was observed in mice and rats. These were probably due to retarded fetal growth rather than to a specific effect of the ethanol. Teratogenic effects were not observed in any of the three species.
Folate antagonism following teratogenic exposure to diphenylhydantoin
Authors: Netzloff Michael L. , Streiff Richard R. , Frias Jaime L. , Rennert Owen M. 
Published: June 2005

AbstractPrevious studies have reported indirect evidence for the mediation of folate antagonism in the induction of malformations by diphenylhydantoin. We have demonstrated that a teratogenic regimen of folate‐deficiency and antagonism using 9‐methyl PGA in the rat produces significantly decreased rates of oxygen consumption in the maldeveloping embryos. The present study reports similar reductions in oxygen uptake by mouse embryos from mothers treated with teratogenic doses of diphenylhydantoin, and documents a significant depression of the actual folate levels in such embryos. The differences are less significant with lower doses of diphenylhydantoin, and do not occur with a nonteratogenic dose.