bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pathogenesis of cleft lip and its relation to embryonic face shape in A/J and C57BL mice
Authors: Trasler Daphne G. 
Published: June 2005

AbstractA comparison was made of early face embryology in the inbred A/J mouse strain with a spontaneous frequency of about 12% cleft lip and the C57BL/6J strain which virtually never has cleft lip. From the time of their appearance the medial nasal, lateral nasal and maxillary processes are connected by an isthmus. Subsequently there is fusion between the adjacent epithelia of medial and lateral nasal processes. Failure of this fusion, followed by breakdown of the isthmus, results in cleft lip. Just before and when the adjacent epithelia of medial nasal and lateral nasal processes meet and fuse at the posterior end of the nasal pit, the medial nasal processes of A/J embryos were more prominent, more medially placed, and diverged less than those of C57BL/6J. It is suggested that (a) cleft lip is a threshold character or quasi‐continuous variant such that a very slight change in the divergence of the medial nasals leads to their partial or complete lack of fusion with the lateral nasals. This is followed by a lack of fusion of medial and maxillary processes, and a complete or partial breakdown of the isthmus, resulting in a cleft lip; (b) the strain differences in type of aspirin‐induced cleft lip and in topography and growth of the facial processes between the two strains are causally related to the A/J predisposition to cleft lip.
Studies on metabolism and identification of the causative agent in aspirin teratogenesis in rats
Authors: Kimmel Carole A. , Wilson James G. , Schumacher Herbert J. 
Published: June 2005

AbstractPregnant Wistar rats treated orally at day 9, 10, or 11 with 250, 500, 750, or 1000 mg/kg aspirin showed a teratogenic dose‐response relation at each treatment time, but a decreased overall embryonic susceptibility as treatment was applied later in gestation. The types of abnormalities produced generally correlated with the state of development at the time of treatment. Treatment of animals at day 9 with 510 mg/kg benzole acid and 2 hours later with 250 or 500 mg/kg aspirin caused a significant increase in percentage of malformations above effects observed after 250 or 500 mg/kg aspirin alone. Determination of free salicylate in embryos and maternal serum after treatment at day 11 with sodium salicylate with or without benzoic acid pretreatment indicated that benzoic acid significantly increased the concentration of salicylate in both embryos and serum 6 and 12 hours after salicylate treatment and throughout the observed period. Thin‐layer chromatography of tissues from these animals revealed only salicylic acid in both embryos and maternal serum, thus implicating salicylic acid as the causative agent in aspirin teratogenesis.
Teratogenic action of acetazolamide in golden hamsters
Authors: Layton W. M. 
Published: June 2005

AbstractThe carbonic‐anhydrase inhibitor acetazolamide was teratogenic for golden hamsters when given in single intraperitoneal doses of from 300‐1200 mg/kg on the 9th day of pregnancy. Most deformities were of the postaxial part of the forelimb. There was a well‐defined dose‐response relation with an ED50 of 695 mg/kg. A sensitive period was demonstrated from 192–210 hours after mating with a peak at 204 hours. The production of this deformity was not associated with a significant embryonic mortality. Acetazolamide is quite specific in that in addition to hand deformities only a few foot deformities and rare cases of exencephaly were produced. In contrast to rats, where acetazolamide‐induced deformities are almost exclusively of the postaxial portion of the right forelimb, the deformity in hamsters occurred in either forelimb, although when a single hindfoot was malformed it was always the left one. The demonstrated sensitive period is during the time of limbbud formation, and the first external signs of deformity were seen as a flattening of the postaxial margins of the limb bud 24 hours after drug administration. The mechanism of action of acetazolamide is not clear since the teratogenic dose probably exceeds the amount needed for complete inhibition of carbonic‐anhydrase activity. The dose needed is also much greater than that used for human therapy, so it does not appear that this drug is a teratogenic hazard for human beings.
Teratogenic effects of methamphetamine in mice and rabbits
Authors: Kasirsky Gilbert , Tansy Martin F. 
Published: June 2005

AbstractPregnant CFI mice and New Zealand White rabbits were given methamphetamine hydrochloride intravenously during days 9–15 and 12–30 of gestation, respectively. Offspring of mice given 5.0 mg/kg on days 9–15 of gestation had less than 2% anomalies. When 10.0 mg/kg were given on days 9–15, a 13.6% incidence of anomalies was observed. Offspring of rabbits receiving 1.5 mg/kg of methamphetamine on days 12–15, 15–20, and 12–30 of gestation showed an incidence of fetal anomalies of 12, 4, and 15.5% respectively. Offspring sired by treated males showed no significant weight change and had no increased anomaly rate.
Effects of fasting and insulin on skeletal development in rats
Authors: Hannah Richard S. , Moore Keith L. 
Published: June 2005

AbstractAcute hypoglycemia was produced in pregnant Holtzman rats, by fasting or fasting plus insulin injections. Rats were fasted for 48 hours beginning on days 7, 9, or 11 of gestation. Examinations of day‐21 fetuses showed that greatest susceptibility to the effects of fasting occurred during gestation days 9 and 10. The effects noted were retarded ossification of the axial skeleton and increased frequency of supernumerary ribs, duplicated vertebral centra, and asynchronous ossification of vertebral centra. Insulin administered during the fasting state produced no further decrease in the ossification rate, but the frequency of supernumerary ribs and duplicated vertebral centra was increased.
Lupin alkaloids from teratogenic and nonteratogenic lupins. II. Identification of the major alkaloids by tandem gas chromatography‐mass spectrometry in plants producing crooked calf disease
Authors: Keeler Richard F. 
Published: June 2005

AbstractThe major alkaloids of lupin plants producing crooked calf disease were identified by tandem gas chromatography‐mass spectrometry and infrared analysis. The gas chromatography peak invariably present in teratogenic plants proved to be anagyrine. A minor but irregular contaminant of the peak was α‐isolupanine. Other alkaloids present but apparently not associated with crooked calf disease were lupanine and two others that were probably epimethoxylupanine and 5,6‐dehydrolupanine.
Teratogenic activity of 2‐amino‐1,3,4‐thiadiazole hydrochloride in Wistar rats and the protection afforded by nicotinamide
Authors: Beaudoin Allan R. 
Published: June 2005

AbstractPregnant Wistar rats were each injected once ip with various doses of 2‐amino‐l,3,4‐thiadiazole hydrochloride (ATDA) at days 1–16 of gestation (sperm day = day 0). The optimal teratogenic dose was determined to be 100 mg/kg and this dose was employed throughout the experiment. At autopsy at day 20 resorptions and malformations were found in all litters from treated females. Two periods of increased embryonic susceptibility to the lethal effects of ATDA were observed. The first at day 5 (100% resorbed) and the second at days 9 and 10 (71.5 and 92.5% resorbed). Periods of increased sensitivity to the teratogenic action of ATDA were at days 9 through 13, when the incidence of abnormal fetuses produced exceeded 90%. The major malformations were anophthalmia, microphthalmia, hydrocephalus, short tail, taillessness, ectrodactyly, syndactyly, and cleft palate. Other malformations occurred occasionally. The malformations were related to the developmental stage at the time of treatment. Supplemental treatment with nicotinamide at days 5, 11, 12, and 13 markedly diminished the teratogenic and lethal effects of ATDA, and at day 11 the administration of nicotinamide completely abolished its teratogenic activity. ATDA probably acts by interfering with NAD‐dependent enzyme reactions.
Alkaline phosphatase activity in fetal hind limbs of the mouse mutation brachypodism
Authors: Krotoski Danuta M. , Elmer William A. 
Published: June 2005

AbstractA reduction in alkaline phosphatase activity was demonstrated histochemically and biochemically in the hind limbs of brachypod fetal mice. Seventeen‐day brachypod tibias had a 2–3‐fold lower alkaline phosphatase activity than controls of a similar age. In mutant femurs of this age the decrease in activity was as much as 3–4‐fold. Brachypod fibulas never demonstrated enzyme activity in the stages studied. The enzyme from mutant limb tissues showed the same kinetics, thermal stability, and electrophoretic mobility as that from non‐mutant tissues. Embryo extract from 13‐day brachypod mice, reported to inhibit the growth of normal rudiments in vitro, had no effect on the activity of the normal enzyme. It is proposed that the reduction in enzyme activity is a secondary effect related to the disruption and retardation of limb development in the mutant.
Correlation of teratogenicity and molecular structure: Ethylenethiourea and related compounds
Authors: Ruddick Joseph A. , Newsome W. H. , Nash L. 
Published: June 2005

AbstractSixteen compounds related to ethylenethiourea and to its parent compound, ethylenebisdithiocarbamate, were investigated to determine the structural requirement for teratogenicity. Modifications of the molecular structure of ethylenethiourea involved altered ring size and added heteroatoms and substituents. Only ethylenethiourea and 4‐methylethylenethiourea were teratogenic, indicating that teratogenicity was intimately linked with the imidazolidinethione structure.
Phenotypic expression of lethal chromosomal anomalies in human abortuses
Authors: Bouié Joëlle , Philippe Emile , Giroud Antoine , Boué André 
Published: June 2005

AbstractFrom anatomical and cytogenetic studies of 1500 spontaneous abortuses attempts were made to establish correlations between the phenotype and karyotype of the specimens. The criteria used to determine the phenotype were based on estimated developmental age and macroscopic and microscopic examinations of embryo and placenta. Main features were described permitting, on anatomic examination of the conceptus, diagnosis of genetic anomalies, and in some instances possibly assigning the type of chromosomal aberration: viz., in monosomy X, triploidies, tetraploidies, and some trisomies. Phenotypic expression at the cellular level was studied by morphometry of the placenta and by study of in‐vitro growth characteristics of cells lines initiated from aneuploid embryos. Study of growth rate characteristics may reveal the basis for the pathogenesis of developmental arrests.
Placental morphology in spontaneous human abortuses with normal and abnormal karyotypes
Authors: Honore Louis H. , Dill Frederick J. , Poland Betty J. 
Published: June 2005

AbstractA systematic gross and microscopic study of the placenta was done on human spontaneous abortions, correlating placental morphology and karyotype of the conceptus. Consistent abnormalities were seen in the four major forms of human heteroploidy, so that a fairly accurate “karyotypic diagnosis” could be made from careful gross and microscopic examination of the aborted material. Depressed growth activity and dysmorphogenesis characterized these placentas, reflecting placental participation in the disturbed phenotypic expression of heteroploidy.
The multifactorial/threshold concept—uses and misuses
Authors: Fraser F. C. 
Published: June 2005

AbstractThe common congenital malformations have familial distributions that cannot be accounted for by simple Mendelian models, but can be explained in terms of a continuous variable, “liability,” with a threshold value beyond which individuals will be affected. Both genetic and environmental factors determine liability, making the system multifactorial. Cleft palate is a useful experimental model, illustrating a number of factors that contribute to palate closure, the nature of a developmental threshold, and how genes and teratogens can alter the components of liability to increase the probability of cleft palate. The nature of the genetic component to liability in human malformations is not clear, and various possibilities, ranging from polygenic in the strict sense to a major gene with reduced penetrance are compatible with the data—but the important feature is the threshold. Much of the confusion over the concept results from inconsistent use of terminology. The term “multifactorial” should be used for “determined by a combination of genetic and environmental factors,” without reference to the nature of the genetic factor(s). “Polygenic” should be reserved for “a large number of genes, each with a small effect, acting additively.” When several genes, with more major effects are involved, “multilocal” can be used. When it is not clear which of these is applicable the term “plurilocal” is suggested, in the sense of “genetic variation more complex than a simple Mendelian difference,” Since teratological data often represent threshold characters the concept also has important implications for the interpretation of data on dose‐response curves, synergisms, and strain differences in response to teratogens.
Exencephaly in fetal hamsters following exposure to hyperthermia
Authors: Kilham Lawrence , Ferm Vergil H. 
Published: June 2005

AbstractExposure of pregnant hamsters on gestation day 8 to 40 or 41°C for one hour caused an increased rate of resorption and a high frequency of exencephaly and encephatocele. Longer exposures often killed pregnant females. Hamsters that had fetuses with abnormalities usually experienced body temperature elevations of 3‒4°C above normal (37°C).
An evaluation of the embryotoxic effects of blighted potatoes on chicken embryos
Authors: Jelínek Richahd , Kyzlink Vladimír , Blattný Ctibor 
Published: June 2005

AbstractThe embryotoxic properties of an ethanol extract of boiled potatoes infected with Phytophthora infestans were investigated in White Leghorn chicken embryos, using controlled subgerminal injection on the second day of incubation and intraamniotic injection on the third and fourth days. A dose of 0.3 mg of sublimation‐dried extract interfered at the somite stages with the function of the caudal morphogenetic system and induced various degrees of the caudal regression syndrome. Administration on the third and fourth days led to the development of a malformation syndrome comprising cranioschisis, celosoma, and cardiac septal defects. An equivalent amount of extract of healthy potatoes of the same variety and injection of pure solanine had the same effect. The results warrant the claim that the main factor responsible for the direct embryotoxicity of potatoes attacked by P. infestans is solanine, which evokes tonic contract ion of the smooth muscle elements of the amnion.
Teratogenicity studies on late blighted potatoes in nonhuman primates (Macaca mulatta and Saguinus labiatus)
Authors: Allen J. R. , Marlar R. J. , Chesney C. F. , Helgeson J. P. , Kelman A. , Weckel K. G. , Traisman E. , White J. W. 
Published: June 2005

AbstractFemale rhesus monkeys and marmosets were fed a diet containing blighted potatoes (Phytophthora infestans) at a level of 10 g/kg per day for at least two weeks prior to breeding and six weeks following conception in order to gain additional information on the association of blighted potatoes and the development of anencephaly and spina bifida in primate species. There was an absence of either of these neural‐tube defects in 32 rhesus and 14 marmoset infants whose mothers had received a blighted potato diet. In addition there were no cranial osseous defects. There were, however, two rhesus monkey infants with internal hydrocephalus whose mothers had consumed blighted potatoes.
Prenatal toxicity of medroxyprogesterone acetate in rabbits, rats, and mice
Authors: Andrew F. D. , Staples R. E. 
Published: June 2005

AbstractMedroxyprogesterone acetate (MPA) was given once daily sc at 0.1–3,000 mg/kg/day for 3, 6, or 9 consecutive days during gestation days 7 to 15 to GDI and A/J mice, and New Zealand (NZ) and Dutch Belted (DB) rabbits, and during days 8 to 16 to CD rats. Malformations attributable to MPA did not occur in fetuses of mice or rats exposed to the largest dosage tested. However, 1, 3, or 10 mg/kg on days 13 to 15 to NZ rabbits resulted in 6, 28, and 42% cleft palate, respectively. Comparable cleft palate frequencies were seen in DB offspring.
Vater syndrome: Hypothesis and report of two further cases
Authors: Lloyd David J. , McKenzie John , Kaye Henry H. , Russell George 
Published: June 2005

AbstractTwo cases are reported of the association of a group of abnormalities defined as the Vater syndrome, together with a hypothesis, based on the presence of normal cell death during embryogenesis, on how they occur together so frequently. Althouh the medhanism of normal cell death is unknown, adjacent cells are probably affected sublethaly and subsequently recover. A teratogenic situation introduced simultaneously with the occurrence of normal cell death may further diminish the viability of those adjacent cells, causing increase in the necorotic zone and loss of both normal tissue and growth potential.
Human fetal development between 90 and 170 days postmenses
Authors: Golbus Mitchell S. , Berry Leonard C. 
Published: June 2005

AbstractLinear measurements, total weights, and organ weights of 133 fresh human fetuses were obtained after therapeutic abortion between 90 and 170 days postmenses. Great apparent variation was observed in fetuses of given ages, especially in organ weights. There was no evidence of sex or parity differences.
Comparison of the effects of retinol and retinoic acid on postimplantation rat embryos in vitro
Authors: Morriss G. M. , Steele C. E. 
Published: June 2005

AbstractRat embryos were explanted on day 8 or 9 of pregnancy and cultured for up to 48 hours in serum containing added retinol (vitamin A), retinoic acid (vitamin A acid), or absolute ethanol. They were examined morphologically and their protein content determined. Retinoic acid was more teratogenic and growthretarding than retinol. Electron microscopy of embryos cultured for 30 minutes or one hour revealed that both forms of vitamin A brought about similar ultrastructural effects on the embryonic cells; however, the abnormally large intracellular lipid droplets observed in a previous study following exposure to retinol in vitro and retinyl palmitate in vivo were not observed in embryos exposed to retinoic acid. It is possible that the differential teratogenicity may be due to the inability of the embryonic cells to convert and store retinoic acid in a less teratogenic form.
Drug‐induced limb dysplasias in fetal rabbits
Authors: Desesso John M. , Jordan Robert L. 
Published: June 2005

AbstractPregnant New Zealand White rabbits were treated on gestation day 12 with 19.2 mg/kg methotrexate (MTX), 750 mg/kg hydroxyurea (HU), or 1,500 mg/kg acetazolamide. Rabbits were killed either 2–32 hours posttreatment for histological analysis of embryos or at day 29 for gross and skeletal examination of fetuses. MTX produced cleft palate, hydrocephalus, and fore‐ and hindlimb reduction defects. Histological analysis revealed pyknosis and edema in mesenchymal tissues at four to eight hours following treatment. The apical ectodermal ridges (AER) of treated embryos permanently lost their characteristic pseudostratified organization. By 32 hours the limb buds had regained their normal appearance except for the AER. HU affected all fetuses with skull and facial anomalies as well as severe reduction deformities of all limbs. Histologically HU‐treated embryos had numerous, basophilic, intercellular granules (presumably cell debris) which appeared within two to four hours in the limb bud mesenchyme, neural tube, and dorsal root ganglion. The architecture of the AER was unchanged. Acetazolamide produced bilateral retarded ossification or possible aplasia of the first metacarpal and talus in nearly 80% of fetuses. Microscopic examination disclosed no apparent alterations in limb‐bud morphology. Methyl green‐pyronin Y staining called attention to green intracellular droplets within the endoderm of the trachea and bronchi at two hours posttreatment. It was concluded that the three drugs do not produce limb dysplasias by a common teratogenic mechanism.
Palatomandibular and maxillo‐mandibular fusion, partial aglossia and cleft palate in a human embryo. Report of a case
Authors: Shah Ravindra M. 
Published: June 2005

AbstractA 32‐mm CRL male human embryo was examined for malformation. Histological observation showed fusion between the left vertical palatal shelf and mandible and the maxilla and mandible in the posterior part of the oronasal cavity. The right shelf was horizontal anteriorly, vertical posteriorly and changing its position from a vertical to a horizontal plane in the middle. The tongue was underdeveloped anteriorly and completely absent posteriorly. The mandibular tooth buds were not formed. Both clinical and experimental literature were analyzed to find the mechanism of statu nascendi defect observed in the present case. It was deduced that the tongue may not play an active role during normal palatal development and that it may not have played any role during the fusion between different intraoral structures observed in the present case. It was concluded that, had the embryo developed further, then at the birth a cleft palate, partial aglossia and associated intraoral malformation would have been expected.
Litigation‐produced pain, disease and suffering: An experience with congenital malformation lawsuits
Authors: Brent Robert L. 
Published: June 2005

AbstractThe exponential rise in malpractice litigation is due to attitudes and happenings in the medical, legal and lay sectors of our society. Evaluation of congenital malformation lawsuits provides a unique opportunity to evaluate the process of litigation. Because the cases are rarely meritorious, the litigation process is detrimental to the plaintiff, society and frequently unfair to the defendant. There is no area of our legal system with such a high percentage of innocent defendants. When the family of a malformed infant becomes orchestrated by an attorney into a position of devoting their energy to winning a lawsuit, many high priority family responsibilities may be ignored and important ethical standards are distorted. To win at all costs may be appropriate for a football team but it can be detrimental to a family. The family enters the litigation arena unaware of the lengthiness of the litigation process and ignorant of the fact that only a small portion of the malpractice premium dollar ever reaches the patient. The plaintiffs are not the only participants who lose their objectivity and lower their ethical standards. The quality and veracity of the testimony of expert witnesses has deteriorated to the point that drastic corrective measures have to be instituted. It is believed that recommendations for solving the malpractice crisis, which are based on the experience with congenital malformation lawsuits, should have applicability to the overall malpractice problem and must involve changes in the medical, legal and lay sectors of our society. These recommendations are discussed in detail. It must be recognized that it is difficult to alter the laws and procedures that are not of benefit to the legal profession because so many legislatures are dominated by elected officials who happen to be attorneys. But it is emphasized that of all the recommendations put forth, the one having the greatest beneficial effect on the present malpractice crisis would be the elimination of the contingency fee system and replacing it with no‐fault compensation or legal‐fee insurance. The contingency fee system provokes and promotes malpractice litigation. The process of litigation rarely solves the patient's problems and frequently develops into a disease all its own.