bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation between the growth inhibitory effects, partition coefficients and teratogenic effects of lipophilic acids
Authors: Freese E. , Levin B. C. , Pearce R. , Sreevalsan T. , Kaufman J. J. , Koski W. S. , Semo N. M. 
Published: June 2005

AbstractThe inhibition of cell duplication by many lipophilic acids was measured in Bacillus subtilis and in the following mammalian cell lines, the hunran epithelial‐type cell lines HeLa, strain R and strain L‐132, the human fibroblast cell line VA‐13, and the rat glial cell line C. The results were correlated to the partition coefficient and the distribution coefficient (= apparent partition coefficient at pH 7.2) of the compounds, using octanol/water partition coefficients and pKa values either from the literature or measured for this work. For B. subtilis, the logarithm of the inhibitory potency of most compounds increases linearly with the logarithm of the partition coefficient. Exceptional high potencies were observed for compounds that can efficiently delocalize the charge of the negative ion over the whole molecule. Most compounds inhibit tissue cultures at least as potently as they inhibit B. subtilis. But some compounds are significantly more potent in tissue cultures than would have been expected from the B. subtilis data; such compounds (analgesics/antipyretics, anti‐inflammatory compounds, but rate, norepinephrine) presumably inhibit mammalian cells by specific reactions with certain cell components. However, most compounds inhibit the different cell lines to a similar degree, indicating no cellular specificity; exceptions to this rule are chlorambucil, chlortetracycline and dexamethasone.Many of the lipophilic acids that are potent inhibitors of mammalian cell replication are also teratogenic. Exceptional compounds may not reach the embryo. We propose that a number of other lipophilic acids that are potent inhibitors and to which humans are frequently exposed should be tested for their teratogenic effect.
A study of spontaneoulsy aborted twins
Authors: Livingston J. E. , Poland B. J. 
Published: June 2005

AbstractFifty‐three pairs of twins were obtained during examination of 1,939 spontaneously aborted complete embroys and fetuses. Therefore, the rate of twinning in pregnancies which spontaneously aborted was about 1 in 35. The spontaneous twin abortions consisted of 25 sets of twin embroys, 26 sets of twin fetuses, and two sets in which one was an embryo and one was a fetus. It was possible to determine the zygosity in 37 pairs. The ratio of monozygotic to dizygotic was 17.5:1. About 88% of the twin embryos and 21% of the twin fetuses were abnormal. These abnormality rates were similar to those observed in the overall study of the abortuses. The data on spontaneously aborted twins were compared with data on liveborn twins. The results suggest that twinning, particularly MZ twinning, occurs more frequently than has been thought, based on newborn data, and that embryonic and fetal mortality is much higher in twins than in singletons.
Dermatoglyphic abnormalities in the fetal alcohol syndrome
Authors: Qazi Qutub H. , Masakawa Akiko , McGann Barbara , Woods James 
Published: June 2005

AbstractDermatoglyphics of 19 male and 23 female patients with fetal alcohol syndrome were compared with those of matched controls. Both male and female patients differed in several of the dermatoglyphic characteristics from their sex‐matched controls. The abnormalities of dermatoglyphics reported here constitute a valuable marker trait of the teratogenic effect of the alcohol on fetal development and provide additional diagnostic signs for the fetal alcohol syndrome.
Genetic maternal effects on cleft lip frequency in A/J and CL/Fr mice
Authors: Juriloff D. M. , Fraser F. C. 
Published: June 2005

AbstractTwo related strains of mice, A/J and CL/Fr, differ in the frequency of spontaneous cleft lip produced in term fetuses: 10% versus 25%. In order to examine the nature of the genetic basis for this difference, various crosses between the strains were made. The results indicated that genes acting in the mothers, rather than in the embryos, caused the strain difference, and that their effect may be on CL(P) embryo survival rather than occurrence. The A/J strain alleles were dominant to those of CL/Fr, and a one‐locus difference can explain the data.The importance of genetic maternal effects on CL(P) frequency in mice, with dominance, should be borne in mind when the polygenic, additive threshold model is applied to human data. Neither effect is allowed within the model, yet if the traits are homologous between species, these effects may well be present in man as in the mouse.
The use of cultured rat embryos to evaluate the teratogenic activity of serum: Cadmium and cyclophosphamide
Authors: Klein Norman W. , Vogler Mary A. , Chatot Clare L. , Pierro Louis J. 
Published: June 2005

AbstractHead fold stage rat embryos were cultured for 48 hours in vitro on serum taken at various intervals from rats that had been injected ip with either cadmium or cyclophosphamide. Their response was compared to that of embryos cultured for the same period on control serum to which these substances were added directly. One and 4 hour sera from cadmium‐injected rats (2.13 mg Cd++/kg) were lethal. Eight hour serum allowed survival but embryos were exencephalic and contained reduced amounts of protein and DNA. The response to direct cadmium was characteristically different and was related to dosage and the extent to which zero‐time embryos had progressed through the head fold stage. At 1.6 μM, Cd++ susceptible embryos were hemorrhagic, though not exencephalic. One hour serum from rats given cyclophosphamide (180 mg/kg) was lethal. On 4 hour serum, embryos survived but were exencephalic and contained less protein and DNA than controls. Embryos were resistant to direct cyclophosphamide up to 800 μg per ml of medium. At this concentration, embryos appeared morphologically normal but contained reduced amounts of protein.
Teratogenicity of diphenylhydantoin in the New Zealand white rabbit
Authors: McClain R. M. , Langhoff L. 
Published: June 2005

AbstractThe teratogenic potential of diphenylhydantoin sodium (DPH) was investigated in the rabbit after oral intubation of 0 (Control), 25, 50, 75, 100, and 150 mg/kg/day from days 7–18 of gestation. Except for reduced maternal weight gains at the two higher dosages, no other obvious pharmacological or toxic effects were noted in treated rabbits.Dose‐response‐related increases in the resorption and malformation rates were observed. Four litters (one of 14 litters with viable fetuses at 75 mg/kg/day and three of eight litters with viable fetuses at 100 mg/kg/day) exhibited a similar pattern of multiple malformations that included some or all of the following defects: open eyes, cleft palate, and limb abnormalities that included shortened and curved long bones, pes caves, syndactyly, and ossification defects of the phalanges. Dosages of 150 mg/kg/day produced nearly complete resorption, which may have masked the teratogenic response to the drug.
Influence of formaldehyde and sonacide® (potentiated acid glutaraldehyde) on embryo and fetal development in mice
Authors: Marks Thomas A. , Worthy William C. , Staples Robert E. 
Published: June 2005

AbstractPregnant outbred albino mice were given formaldehyde or Sonacide® (potentiated acid glutaraldehyde) by gavage on days 6–15 of gestation. The mice were killed on day 18, the general health and reproductive status of the dam evaluated, and the fetuses examined and processed in order to characterize external, visceral, and skeletal malformations. Although formaldehyde (stock solution containing 12–15% methanol as a preservative) was lethal to 22 of 34 dams treated with 185 mg/kg/day, and one of 35 dams treated with 148 mg/kg/day, these doses did not produce statistically significant (two‐sided p < 0.05 versus controls) teratogenic effects in the fetuses of the surviving dams. Sonacide® was also judged not to be teratogenic to the mice employed in this study, in spite of the fact that relatively high doses were employed. The highest doses of Sonacide® studied (5.0 ml/kg/day, which is equivalent to 100 mg/kg/day of glutaraldehyde) killed 19 of 35 dams and caused a significant reduction in the mean weight gain of the surviving mothers. In addition, this dose produced a significant increase in the number of stunted fetuses.
The effects of cytochalasins on the ultrastructure of neurulating hamster embryos in vivo
Authors: Wiley M. J. 
Published: June 2005

AbstractSingle intraperitoneal injections of cytochalasin B (CB) in dimethylsulfoxide were given to gravid Syrian hamsters on the eighth day of pregnancy at various dose levels. Exencephaly and encephalocele, the only defects which were seen in the term litters, occurred in dose‐response patterns reaching peak frequencies of 14.9% and 53.2%, respectively, at the highest dose level, while accompanied by a mortality of 27.7% of implantations. Although these abnormalities were the same as those resulting from cytochalasin D (CD) treatment at this time, the frequencies were lower and the distribution of defects somewhat different. Morphological comparison of embryos fixed at various times after maternal treatment with 7.0 mg/kg CB or 1.5 mg/kg CD demonstrated qualitatively similar changes in response to either teratogen, leading to failure of the cranial neural folds to approximate and close. The principal ultrastructural changes involved alterations in the topography of the apical membranes of neuroectoderm cells. At doses which produced high frequencies of gross defects in the term litters, no changes were seen in the apical bundles of microfilaments in these cells, although much higher dose levels did disrupt these structures. The results support the hypothesis that the cell membrane is the primary target of these teratogens in vivo.
The fetal alcohol syndrome in mice: Maternal variables
Authors: Chernoff Gerald F. 
Published: June 2005

AbstractCBA, C3H, and C57 female mice maintained on a diet of 20 percent ethanol‐derived calories prior to and throughout gestation were mated in a diallele cross. Prenatal death, malformations, and fetal weights were directly related to maternal blood alcohol levels, indicating a maternal effect. Fetal abnormalities and maternal blood alcohol levels varied with maternal strain (CBA > C3H > C57) and were inversely related to maternal alcohol dehydrogenase activity. Microsomal ethanol oxidizing systems induction was directly associated with increased fetal abnormalities, being greatest in CBA females. These results indicate that liability for the pattern of malformation observed in this syndrome is dependent on maternal blood alcohol levels, which are determined by the rate of maternal alcohol metabolism as well as the amount of maternal alcohol consumption.
Anatomical defects in a case of trisomy 13 with a D/D translocation
Authors: Aziz M. Ashraf 
Published: June 2005

AbstractGross morphological defects and variations in a cytogenetically confirmed case of trisomy 13 with t (D/D) are described comprehensively for the first time. The subject, a female neonate, exhibited the following clinical features: microcephaly, sloping forehead, coloboma of the iris, bilateral cleft lip and palate, short neck, and postaxial extra digits on hands and feet. Visceral anomalies included: dextrocardia; hypertrophied right ventricle; common atrium; hypertrophied sinus venosus; persistent left superior vena cava; a large, patent ductus arteriosus interventricular septal defect; Meckel diverticulum; common mesentary; omphalocele; accessory renal arteries and veins; bicornuate uterus; bilateral agenesis of the olfactory bulb; partial holoprosencephaly; and the ulnar nerve passed anterior to the medial epicondyle, bilaterally. Supernumerary muscles included: pectorodorsalis (“achselbogen”); chondroepitrochlearis; sternochondroscapularis; accessory heads of biceps brachii; and radiocarpus. The following muscles were absent: stylohyoideus; pectoralis minor (left); subclavius; palmaris longus and brevis; plantaris; and peroneus tertius. The following muscles exhibited unusual variations: digastricus; mylohyoideus; pectoralis major; and extensor indicis. These findings are compared and contrasted with those recently reported in primary trisomy 13 and 18 and with a case of trisomy 13 with a D/G translocation.
Regional differences in the effects of glucocorticoids on maturation of the fetal skeleton of the rat
Authors: Mosier H. David , Dearden Lyle C. , Roberts Rosalinda C. , Jansons Regina A. , Biggs Cynthia S. 
Published: June 2005

AbstractThe effects of glucocorticoids on fetal growth and development in the rat were investigated. Pregnant rats were injected subcutaneously on gestational days 12 and 13 with betamethasone (0.18 or 0.42 mg), with dexamethasone (0.12 or 0.24 mg), or with physiological saline. Fetuses at day 21 of gestation were weighed, cleared, and stained for calcification with Alizarin Red S. Fetal weight was significantly reduced at both dose levels of each steroid; a greater reduction occurred with the higher dose. Retardation of growth and of calcification of bones in the axial skeleton occurred at both doses; there was greater retardation with the high dose. In the appendicular skeleton there was enhanced calcification of some bones with the low dose, and a retardation of calcification with the high dose of each steroid.The present findings show that different regions of the fetal skeleton may respond discordantly to the effect of glucocorticoids depending on the dose.
The effect of vitamin A on fusion of mouse palates. II. Retinyl palmitate, retinol, and retinoic acid in vitro
Authors: Newall D. R. , Edwards J. R. G. 
Published: June 2005

AbstractA fixed‐exposure culture technique is described using palatal shelves removed from mouse fetuses on day 14 of pregnancy. In this technique growth is eliminated as a possible variable. The addition of retinyl palmitate, retinol, or retinoic acid to culture medium at concentrations similar to those found associated with cleft palates produced in vivo after dosing dams with vitamin A on day 14 prevented fusion of explanted shelves in vitro after a 24‐hour exposure period. Retinoic acid prevented fusion of explants after as little as 4 hours exposure. Retinoic acid was more active in vitro than retinol, which was itself eight to ten times more active than retinyl palmitate. An explanation of the effect of vitamin A on the fusing mouse palate is given based on altered glycoprotein synthesis.
Effect of retinoic acid upon the chick embryonic morphogenetic systems. I. The embryotoxicity dose range
Authors: Jelínek R. , Kistler A. 
Published: June 2005

AbstractThe effects of all‐trans‐beta‐retinoic acid upon the developing chick embryo were investigated using the Chick Embryotoxicity Screening Test (CHEST). A dose of 0.3 μg, injected subgerminally in stages HH 10–11, arrested the neural tube development, disturbed extraembryonic vasculogenesis, and induced formation of haemorrhagic blisters in the caudal region. Single administration of retinoic acid on days 2,3, and 4 revealed a stage‐specific effect. Being high, due to the abundant mortality of embryos injected on day 2, the effect drops conspicuously on day 3, and rises once again on day 4 when a remarkable proportion of the surviving fetuses suffer from serious morphological damage comprising cardiovascular lesions, maldevelopment of the central face, and dysmelia. The target tissues are similar to those of vitamin A in developing mammals. The increased sensitivity of chick embryo morphogenetic systems between days 3 and 4 supports the hypothesis that the deleterious action of retinoic acid is due to the development of specific binding sites in the target cell populations.
Comparative ultrastructural alterations in rabbit limb‐buds after a teratogenic dose of either hydroxyurea or methotrexate
Authors: Desesso John M. 
Published: June 2005

AbstractEarly changes in rabbit limb‐bud fine structure subsequent to maternal administration of either hydroxyurea (750 mg HU/kg) or methotrexate (19.2 mg MTX/kg) on gestational day 12 have been analyzed in order to identify the morphologic sites of teratogenic action. Forelimb‐buds were examined at 15 minutes to 32 hours posttreatment for ultrastructural alterations. HU caused early dispersion of ribosomes, condensation of nuclei, segregation of the granular portion of the nucleoli, and eventual fragmentation of mesenchymal cells. As a consequence of the extensive mesenchymal cellular death, the intercellular space among the remaining viable cells was increased. Cellular debris from fragmented cells was seen phagocytized within cells and in the intercellular space. In contrast, MTX caused an increase in cytoplasmic lipid, angular contours of nuclei, but relatively little cellular death. The most prominent change was a disruption of the normal mesenchymal architecture characterized by greatly increased intercellular space and a consequent reduction in the number of intercellular junctions. Nearly normal cytoarchitecture was restored by 32 hours. It was concluded that the primary morphologic sites of action are indeed different. Nevertheless, MTX and HU shared a common denominator since both caused disruption of intercellular contacts and possible breakdown of intercellular communication: HU through cytolethality, and MTX via disruption of intercellular junctions. This latter phenomenon may help to explain the similarities in limb defects caused by these two drugs.
Comment on the prune belly syndrome: An 11‐week fetus with megacystis
Authors: Barr Mason , Burdi Alphonse R. 
Published: June 2005

AbstractAn 11‐week human fetus with megacystis, prostatic dysgenesis, and lateral displacement of the abdominal muscles is described. We suggest that a subtle outflow obstruction of the very early bladder may give rise to both bladder dilation and bladder wall dysgenesis. The bladder dilation may produce abdominal muscle dysplasia or atrophy and almost certainly produces dilation of the prostatic urethra. The dilation of the prostatic urethra disrupts the formation of the prostate.
Teratogenic effects of aliphatic nitriles
Authors: Willhite Calvin C. , Ferm Vergil H. , Smith Roger P. 
Published: June 2005

AbstractIntraperitoneal injection of acrylonitrile at 1.51–2.26 mmole/kg (80–120 mg/kg) or propionitrile at 0.54–1.51 mmole/kg (30–83 mg/kg) on the morning of Day 8 of gestation in the hamster induced exencephaly, encephalocoeles, and rib fusions and bifurcations in the offspring. These doses of the aliphatic nitriles also resulted in obvious toxicity to the dams. Multiple intraperitoneal injections of sodium thiosulfate at 4.03 mmole/kg (1 gm/kg) protected both dams and embryos against toxicity. When the larger doses of either acrylonitrile or propionitrile were given in the presence of sodium thiosulfate, teratogenic effects were observed in the absence of overt signs of maternal poisoning. A survey of the literature describes many studies which demonstrate that acrylonitrile and propionitrile are converted in vivo to toxicologically significant concentrations of cyanide and that sodium thiosulfate, an established cyanide antagonist, can provide protective actions against poisoning by either acrylonitrile or propionitrile. The observations suggest that the teratogenic effects of both acrylonitrile and propionitrile are related to the metabolic release of cyanide.
Diazepam‐induced neural tube closure defects in explanted early chick embryos
Authors: Nagele R. G. , Pietrolungo J. F. , Lee H. , Roisen F. 
Published: June 2005

AbstractThe effects of diazepam on the development of explanted stage 4 chick embryos were investigated. Diazepam, at 10–120 μg/ml, preferentially inhibited closure of the neural tube. This effect was reversible. Concentrations of 150–200 μg/ml inhibited not only neural tube closure but also blastodermal expansion, somite formation, and heart development in 52% of the embryos. Concentrations above 200 μg/ml were highly embryotoxic. Electron microscopy of affected neuroepithelial cells revealed that (1) apical surfaces were much smoother than usual and (2) apical filament bundles, which are generally thought to provide motive forces for uplifting of neural folds, were not well organized and often lacked alternating dark and light areas along their length. These findings and the fact that changes in cell surface topography reflect the contractile activities of underlying filament bundles suggest that the observed “smoothing” effect on apical cell surfaces and neural tube closure defects are due, at least in part, to the impaired ability of these filament bundles to contract.
Modification of the teratogenicity and mutagenicity of cyclophosphamide with thiol compounds
Authors: Hales Barbara F. 
Published: June 2005

AbstractCyclophosphamide must be metabolized to have either therapeutic or toxic effects; many of the major metabolites of cyclophosphamide interact with thiol compounds. To characterize the relationship between the teratogenic and mutagenic metabolites of cyclophosphamide, the effect of thiol compounds on the teratogenicity and mutagenicity of this drug was studied. The effect on teratogenicity was assessed in vivo by treatment of rats with thiol compounds or thiol‐depleting agents prior to administration to cyclophosphamide on day 13 of gestation. The effect on mutagenicity was measured in vitro with a bacterial mutagenicity test using Salmonella typhimurium TA 1535. The administration of thiol compounds (glutathione or cysteine) decreased the teratogenicity of cyclophosphamide, whereas the administration of a thiol‐depleting agent (diethyl maleate) increased its teratogenicity. Low concentrations of glutathione (0.1–1.0 mM) increased the mutagenicity of cyclophosphamide; this effect was not observed with S‐methylglutathione or other thiol compounds. Higher concentrations of glutathione (10 mM, reduced or oxidized) and cystine, but not cysteine, decreased the mutagenicity of cyclophosphamide. Reduced dithiothreitol also decreased the mutagenicity of cyclophosphamide but was toxic in experiments in vivo so its effect on teratogenicity could not be evaluated. Thus, thiol compounds modify both the teratogenic and mutagenic effects of cyclophosphamide. Low concentrations of glutathione (the addition of glutathione in mutagenicity experiments or the depletion of endogenous glutathione in teratogenicity experiments) increased both the mutagenicity and the teratogenicity of cyclophosphamide, whereas high concentrations of this or other thiol compounds decreased these toxic effects. It may be possible to exploit the protective effect of thiol compounds clinically by using thiols to protect pregnant women from the teratogenic effects of inadvertent or intentional administration of cyclophosphamide.
Genetic aspects of the effects of methylmercury in mice: The incidence of cleft palate and concentrations of adenosine 3′:5′ cyclic monophosphate in tongue and palatal shelf
Authors: Harper Kenneth , Burns Risa , Erickson Robert P. 
Published: June 2005

AbstractConcentrations of adenosine 3′:5′ cyclic monophosphate (cAMP) were measured in the tongues and palates of 14.5‐day‐old fetuses from control and methylmercury‐treated mothers of four inbred lines of mice which represent the four possible combinations of two H‐2 alleles and two residual genetic backgrounds. The incidence of cleft palate in fetuses from control and methylmercury‐treated mothers was also examined. The H‐2 alleles significantly affected the degree of reduction of cAMP concentration in palates seen in fetuses from mothers treated with methylmercury. Neither the H‐2 allele nor the residual genetic background played a role in the effect of methylmercury on cAMP concentrations in fetal tongues. The magnitude of increase in the incidence of cleft palate with methylmercury treatment was approximately the same for all lines. Thus, methylmercury‐induced cleft palate may not be mediated by the reduction of cAMP. Finally, fetuses with cleft lip had increased palatal cAMP levels, whether or not they were from control or methylmercury treated mothers.