bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of the time allowed for mating on variability of fetal weight in rats
Authors: Barr Mason 
Published: June 2005

AbstractIn rats variation of fetal weights among litters is significantly greater than variation of fetal weights within litters. This phenomenon is called the litter effect. Twenty litters of Wistar rats were studied to determine whether or not variation in the duration of the period allowed for copulation (1.5 hours versus 15 hours) was a cause of the litter effect. Analyses of variance showed that the duration of the mating period did not significantly influence mean fetal weight, intralitter variability, or interlitter variability. It is concluded that the use of a restricted mating period as opposed to the commonly used overnight mating period offers no advantage from the standpoint of fetal weight variability. The need to consider the sample size of both litters and fetuses in teratologic and fetal growth studies is stressed.
Teratogenesis and inhibition of DNA synthesis induced in rat embryos by cytosine arabinoside
Authors: Ritter Edmond J. , Scott William J. , Wilson James G. 
Published: June 2005

AbstractPregnant Wistar rats were injected at day 12 of gestation with 25, 50, 100, or 200 mg/kg cytosine arabinoside. One to 27 hours later 3H‐thymidine was also injected followed 2 hours later by surgical removal of one uterine horn. The remaining horn was left in situ until day 20 for evaluation of embryotoxicity (malformation, death, or growth retardation). Half of the embryos in the removed horn were prepared individually for whole‐embryo scintillation counts and the other half were homogenized and treated with perchloric acid, of which the acid‐insoluble fraction was quantitated for 3H‐thymidine incorporation by scintillation counting. Other pregnant rats were treated with cytosine arabinoside and allowed to continue to day 20 without further treatment.Twenty‐day fetuses from females given cytosine arabinoside at day 12 showed dose related malformation and growth retardation but not death following 50 to 200 mg/kg. These effects were more severe when treatment was followed by thymidine injection and partial hysterectomy. The latter procedures revealed striking and dose related suppression of DNA synthesis evidenced by 3H‐thymidine incorporation 1 to 27 hours after cytosine‐arabinoside injection. Embryotoxic effects in 20‐day fetuses were more closely related to the cumulative suppression of DNA synthesis caused by a given dosage than with either the level at any one posttreatment interval or the duration of the suppression. Although all dosages caused reduction in the rate of DNA synthesis to less than 25% of control rate 1 hour following treatment, after the smaller dosages recovery to control rate occurred by 15 hours whereas after 200 mg/kg recovery was not complete even after 27 hours. Surprisingly, 12‐day rat embryos exhibited suppression of DNA synthesis of between 25 and 75% of control rate for up to 9 hours with little effect being apparent in 20‐day fetuses.
Induction of cleft palate in rats with antiinflammatory drugs
Authors: Walker Bruce E. 
Published: June 2005

AbstractPregnant Holtzman rats were injected subcutaneously with anti‐inflammatory drugs from days 12–15 of gestation. Daily doses producing significant frequencies of cleft palate in the offspring ranged from 0.1–0.8 mg/day for triamcinolone, betamethasone, and dexamethasone. Cleft palate was not induced by methylprednisolone, prednisolone, and cortisone, even by daily doses ranging from 8–75 mg. Similar experiments were performed on A/J mice. The possible significance of these experiments in relation to testing potential teratogens and to the mechanism of palate closure is discussed.
Comparative studies on the absorption of 3H‐thalidomide in rabbits and rats
Authors: Keller George R. , Blake David A. 
Published: June 2005

AbstractAn extensive review of the literature revealed that orally administered thalidomide produces a variable teratogenic response in rabbits at equal doses; while rats are uniformly resistant to the teratogenic effects of thalidomide. In an effort to explain these individual and species differences a study was made comparing the oral absorption of 3H‐thalidomide suspension in these species under identical conditions at teratogenic dosage levels (50, 100, and 200 mg/kg). New Zealand white female virgin rabbits and Sprague‐Dawley female virgin rats were employed. Unlike rats, rabbits were quite variable in absorbing thalidomide suspensions, and this was presumably related to the delayed gastric emptying time in some animals. However, the mean plasma concentrations were similar in both species during multiple daily administration of thalidomide suspensions. When thalidomide was administered to rabbits in hard gelatin capsules it was poorly absorbed because of slow dissolution of the powdered drug in gastrointestinal fluids. Regardless of the dosage form administered, only negligible absorption occurred from the rabbit stomach. The small intestine was shown to be the site of absorption in rabbits. These results suggest that the absorption of orally administered thalidomide suspension is so similar in rabbits and rats that it could not be responsible for the species difference in its teratogenic potency. However, the availability of thalidomide from encapsulated powder is so poor in rabbits that the positive teratogenic results recorded in the literature with this dosage form are questionable.
Teratogenicity of structural truncates of cyclophosphamide in mice
Authors: Gibson James E. , Becker Bernard A. 
Published: June 2005

AbstractTruncates of cyclophosphamide including proposed in vivo metabolic products were administered to pregnant mice on day 11 of gestation. Minimal teratogenic dosages were determined: cytoxyl alcohol, 290 mg/kg; cytoxyl amine, 270 mg/kg; phosphoramide mustard, 154 mg/kg; nornitrogen mustard, 1.6 mg/kg; and 3‐amino‐l‐propanol, 5.7 mg/kg. Maternal toxicity was evident in each case. Malformations varied from agent to agent but no agent paralleled cyclophosphamide (20 mg/kg) teratogenicity. Cyclophosphamide produced more frequent and more severe soft tissue and skeletal malformations without maternal toxicity than did any of the cyclophosphamide truncates tested. Common teratogenic effects of cyclophosphamide, cytoxyl alcohol, and nitrogen mustard were polydactyly, oligodactyly, syndactyly, cleft palate, and some skeletal defects. Cytoxyl amine, phosphoramide mustard, nornitrogen mustard, and 3‐amino‐l‐propanol were less teratogenic. Alkylating activities of these agents were determined by nitrobenzyl pyridine reaction in plasma of mice 2, 4, 8, 16, 32, and 64 minutes after intraperitoneal dosages equimolar to cyclophosphamide (100 mg/ kg). No relation between teratogenicity and alkylating potencies of the various agents was demonstrated.
Teratogenic effects of lithium in rats
Authors: Wright T. L. , Hoffman L. H. , Davies J. 
Published: June 2005

AbstractDevelopmental defects were observed in fetuses following intra‐peritoneal administration of lithium chloride to pregnant rats. The resulting malformations were almost exclusively cranial in location, primarily affecting the eye, external ear, and palate. In addition resorption rate was increased. Since this represents the first report of such effects in rats, the results are discussed with respect to previous experiments using lithium in other experimental animals and to the possibility of lithium‐induced teratogenesis in human beings.
Interorbital distance in cleft lip and palate
Authors: Aduss Howard , Pruzansky Samuel , Miller Marilyn 
Published: June 2005

AbstractThe bony interorbital distance (BIOD), as a measure of orbital hypertelorism, was determined for 285 children representing the major categories of cleft lip and/or cleft palate. The BIOD was measured on longitudinal postero‐anterior roentgencephalograms from 6 months to 16 years. There were no significant differences in BIOD between the males and females with complete unilateral and complete bilateral cleft lip and palate or between the combined cleft samples. The BIOD was increased more in those with cleft lip and cleft lip‐cleft palate than in those with only cleft palate. Although patients with clefts had an increased BIOD, in most cases the increase did not exceed 1 SD of that reported for a control group. In unoperated infants no association was found between increased BIOD and the width of the cleft or palate at the level of the maxillary tuberosities. This finding suggested that the BIOD may reflect abnormal development in the nasofrontal process, which also affects the lip but does not include the palatal shelves. Finally, it is suggested that the BIOD is a relevant developmental variable with a threshold character in the etiopathogenesis of cleft lip and cleft lip‐cleft palate.
Present status of drugs as teratogens in man
Authors: Wilson James G. 
Published: June 2005

AbstractThe literature pertaining to the effects of drugs on human in‐trauterine development has been reviewed. As far as quality and quantity of reported evidence permits, four categories of drugs were established, namely, those: (1) positively implicated as teratogenic, (2) suspected of having some teratogenic potential, (3) possibly teratogenic under some conditions, and (4) having little or no teratogenic potential under usual conditions of usage. Although a few compounds were judged to belong in each of the first three categories, it was concluded that drugs taken during pregnancy appear in total to make only a small contribution to the causation of human developmental defects.
Lupin alkaloids from teratogenic and nonteratogenic lupins. I. Correlation of crooked calf disease incidence with alkaloid distribution determined by gas chromatography
Authors: Keeler Richard F. 
Published: June 2005

AbstractA comparison was made by gas chromatography of lupin alkaloid distribution among members of the Lupinus genus that produced crooked calf disease experimentally and those that failed to do so. Further comparison of distribution was made of plants from areas where the disease is common and from areas where the disease is not known. There were alkaloid distribution similarities in all active plants that were not shared by the inactive ones. Four major alkaloid peaks were generally present in active samples, but peak 4 was the only one invariably present in active plants and invariably absent or of low concentration in inactive ones. The data do not positively incriminate an alkaloid as the active principal in the disease, but it is clear that if a major alkaloid is responsible it is the alkaloid of peak 4. That alkaloid is anagyrine. The data further indicate that one can recognize potentially teratogenic lupins by their alkaloid distribution patterns.
Effects of histone on morphogenesis of chick embryonic constituents. I. The teratogenic range
Authors: Hořejší J. , Jelínek R. , Láznička M. , Loštický C. 
Published: June 2005

AbstractTo investigate the claim that the teratogenic effects of histones in chick embryos are limited to a certain period of early development we used total calf thymus histone. After finding that 30 μg were effective at the somite stages, single doses of 0.3, 3, and 30 μg were applied subgerminally on day 2 and intraamniotically on days 3 and 4 to White Leghorn embryos. The teratogenic activity was much greater on days 3 and 4 than on day 2; treatment at the former times produced a characteristic syndrome consisting of cranioschisis, hyperlordosis, eventration, and transposition of the aorta. In view of these findings the opinion that histones lack teratogenic action at later developmental stages is no longer tenable. Furthermore the present results also support the view that the teratogenic effects of histone are caused by mechanisms other than suppression of genomic activity.
Spontaneous pleural effusion in a human fetus
Authors: Barr Mason , Burdi Alphonse R. 
Published: June 2005

AbstractLeft sided pleural effusion was found in a human fetus spontaneously aborted at 20 weeks postmenstrual. Pulmonary hypoplasia associated with the effusion suggested that the fluid had been present for some time before delivery. Absence of other anomalies supports the view that the effusion was due to maldevelopment of the thoracic lymph channels.
Comparative distribution and embryotoxicity of hydroxyurea in pregnant rats and rhesus monkeys
Authors: Wilson James G. , Scott William J. , Ritter Edmond J. , Fradkin Rochelle 
Published: June 2005

AbstractHydroxyurea was given to pregnant rhesus monkeys and pregnant rats in regimens adjusted to produce similar degrees of teratogenicity, for the purpose of comparing the distribution of the drug in the females and their embryos. Accordingly, in rats 137 mg/kg/day ip on days 9–12 resulted in a drug half‐life in maternal plasma of about 15 min and in embryos about 85 min, after the last injection; and in monkeys 100 mg/kg/days iv on days 23–32 resulted in drug half‐life in maternal plasma estimated to be 120 min and in embryos 265 min, after the last injection. Using as a baseline of biological effects the minimal concentration known to inhibit DNA synthesis in rat embryos and cancer cells, namely 10−4 M, it was calculated that the rat embryos in the present study were exposed to this level or more for approximately 12 h whereas the monkey embryos were exposed for approximately 100 h. Although the teratogenic effects were not identical in the two species, these data are interpreted to mean that rat embryos are teratogenically much more sensitive to hydroxyurea than monkey embryos. These observations have important implications in the selection of appropriate species for tests to estimate human teratogenic risks. The rat, which is currently the most widely used animal for such tests, displays sizeable differences from rhesus monkeys, which is one of the animals thought to be most like man in teratogenic susceptibility.
The teratogenic effects of 6‐mercaptopurine on chick embryos in ovo
Authors: Grubb Randall B. , Montiegel Ethel C. 
Published: June 2005

AbstractFertilized eggs of single‐combed White Leghorn hens were each injected through a shell window directly beneath the embryo at 70 or 96 h of incubation with 2 mg of the sodium salt of 6‐MP dissolved in 0.1 M phosphate buffer, and at 11 days of incubation the embryos were examined for gross morphological abnormalities. Various gross malformations and growth retardation were found, the most frequently and severely affected structures being limbs, beak, and eyes. Treatment at 70 h caused more severe abnormalities than at 96 h, but the spectrum of defects was not very different.
The in vivo and in vitro effects of lithium on human chromosomes and cell replication
Authors: De La Torre Rafael , Krompotic Eva , Kowlessard Leslie 
Published: June 2005

AbstractPhytohemagglutinin (PHA)‐stimulated lymphocyte cultures of a healthy human donor, treated in vitro with 0.5, 1.0, and 1.5 mg LiCl/10 ml of culture (equivalent to 1.1, 1.5, and 2.1 mEq/l, respectively) had an increased incidence of chromosomal anomalies and a significant increase in satellite associations, compared with an unexposed culture. The in vivo effects of Li2CO3 on the chromosomes of psychiatric patients on lithium therapy showed increased chromosomal abnormalities, as compared with lithium‐free controls. A significant finding was a marked increase in satellite associations in all lithium‐treated patients. The mitotic index of PHA‐stimulated human lymphocytes exposed to doses of lithium salts (0.5–1.5 mg/10 ml of culture media) was decreased, as measured by [3H]thymidine incorporation into cells.
Accessory spleens in domestic rabbits (Oryctolagus cuniculus). I. Frequency, description, and genetic factors
Authors: Fox R. R. , Weisbroth S. H. , Crary D. D. , Scher S. 
Published: June 2005

AbstractAccessory spleens in 2 separate necropsy series of (a) 1848 randombred rabbits and (b) 21,802 inbred and partially inbred and 880 hybrid rabbits were described and illustrated. The overall frequency in the randombred population (8.9%) was comparable to that in unselected human necropsy series (10%). The predominant locations of accessory spleens in the rabbits (adjacent to the splenic hilus, the gastrosplenic ligament, and the tail of the pancreas) arranged in descending order, were comparable to their locations in human beings. The inbred rabbits had an overall frequency of at least one accessory spleen of 22.5%, similarly located, and ranged from 1–50%, depending on the strain. It was shown by crosses of high‐ and low‐frequency strains that the presence of accessory spleens is due in part to genetic factors and that a high frequency of accessory spleens is probably a recessive characteristic. The latter interpretation is also supported by the fact that the low or “normal” strains had an overall frequency of at least 1 accessory spleen of 8.8% which is in accord with both the randombred rabbit population and human necropsy findings.
Distribution of 203Hg in pregnant and fetal rats
Authors: King Richard B. , Robkin Maurice A. , Shepard Thomas H. 
Published: June 2005

AbstractThe distribution of mercury was studied in pregnant and fetal rats after administration at days 11, 13, and 19 of pregnancy. Methyl‐203Hg‐chloride was used as a tracer to determine amounts of mercury in brain, kidneys, liver, heart, placenta, and whole fetus. The fetal brain was shown to accumulate 19 times more of the amount in the fetus than did the maternal brain the amount in the pregnant female. In addition, the fetal brain concentration was 3.4 times higher than the maternal brain concentration. Clearance studies showed that the organ concentrations were variable with little change occurring in maternal brain and fetus. These results are consistent with sensitivity to mercury damage being greater in the fetal than the maternal brain.
Analysis of fetal development in rats following maternal exposure to subanesthetic concentrations of halothane
Authors: Lansdown A. B. G. , Pope W. D. B. , Halsey M. J. , Bateman P. E. 
Published: June 2005

AbstractPregnant Sprague‐Dawley rats were exposed to 50, 100, 200, 800, 1600, or 3200 ppm halothane on days 8, 9, 10, 11, and 12 of pregnancy. This did not result in increased fetal death and resorption rates, growth retardation, or an increased frequency of skeletal anomalies. When rats were exposed to 1600 ppm halothane on days 1–21 of pregnancy fetal growth was retarded but the differences in the number of centers of ossification in the skeletons were not significant. Skeletal anomalies including supplementary ribs, defective or delayed ossification of sternebrae, and missing centers of ossification in the lower parts of the limbs were seen in some fetuses in all groups but the frequency was not treatment related. Our results indicate that in Sprague‐Dawley rats halothane is not teratogenic or otherwise fetotoxic at subanesthetic concentrations.
Cardiovascular malformations found in 1286 externally normal human embryos alive in utero
Authors: Semba Reiji 
Published: June 2005

AbstractThe heart and great vessels of 1286 human embryos were microdissected and examined for malformations. Most of the embryos were obtained by induced abortion conducted for socioeconomic reasons and the remainder by hysterectomy performed because of some minor disturbance. Only embryos that were alive in utero, at Carnegie stages 18–23, and showed no external anomalies were included. A microdissection procedure that enables precise examination of the heart was used. Criteria for diagnosis of such defects as ventricular septal defect, stenosis, and coarctation were established. Twenty‐seven (2.1%) embryos with congenital cardiovascular malformation (CCM) were found. The frequency was higher than that (0.46–1.17%) reported for newborns. The defects included most of the comparatively common types of CCM, and it was confirmed that the major types of CCM are manifested early in life. It was also noted that certain severe types of anomaly, reported to be scarce in infants, are relatively common in embryos.
Test of the hypothesis that embryonic face shape is a causal factor in genetic predisposition to cleft lip in mice
Authors: Juriloff D. M. , Trasler D. G. 
Published: June 2005

AbstractIt was proposed that embryonic face shape is one of the quantitative variables underlying the threshold trait, cleft lip. To test the hypothesis several facial dimensions were measured in photographs of embryos at an early stage of formation of the face in 3 lines of mice. The lines had been selected from one original population using frequency of cleft lip induced by 6‒aminonicotinamide as the selection criterion. Line L was susceptible to spontaneous cleft lip; lines M and C were not. Line L had a significantly smaller distance between the nasal pits than the other 2 lines, but did not differ in overall head size. A trend towards reduced angle between the medial nasal processes in the L line was noted, though this was not statistically significant. These results were predicted by the face‐shape hypothesis.
The teratogenic effects of β‐aminopropionitrile in hamsters
Authors: Wiley M. J. , Joneja M. G. 
Published: June 2005

AbstractThe teratogenicity of β‐aminopropionitrile (βAPN) was evaluated in golden Syrian hamsters; single doses of 1250, 2500, and 3750 mg/kg given on days 7‒13 produced fetal mortality, growth retardation and malformations. All time‐dose combinations produced gross external abnormalities with the highest rate (92.5%) occurring following day‐12 treatment. High frequencies of skeletal abnormalities including deformities of the ribs, fibula, and scapula occurred after days‐10‒12 treatment. Deformed ribs occurred in 100% of fetuses exposed on day ll to any of the dosages. The types of abnormality generally resembled those produced by lathyrogens in other species except for exencephaly and encephalocele, which occurred after treatment on day 7. These results indicate that βAPN is a typical teratogen, capable of producing abnormalities of the central nervous system early in gestation, and may reflect a broader mechanism for its activity than previously suggested.
Neural‐tube defects caused by 5‐bromodeoxyuridine in chicks
Authors: Lee Hsin‐Yi , Hikida Robert S. , Levin Martin A. 
Published: June 2005

AbstractChick embryos were explanted at HH stage 4 and cultured for 24 h on thin albumen with 10 μg/ml 5‐bromodeoxyuridine (BrdU). BrdU inhibited closure of the neural tube in over 90% of the embryos. Mitotic figures were found throughout adversely effected neuroepithelium, suggesting that interkinetic nuclear migration had been inhibited. Electron microscopic studies of BrdU‐treated neural‐tube cells showed fewer and more amorphous cytoplasmic extensions, microfilaments, and desmosomal (functional) tonofibrils than in controls, but micro‐tubules were unaffected.
Ca‐DTPA‐induced fetal death and malformation in mice
Authors: Fisher Darrell R. , Calder Scott E. , Mays Charles W. , Taylor Glenn N. 
Published: June 2005

AbstractIncreased fetal mortality and congenital malformation were induced in mice by Ca‐DTPA, a chelate widely used for the removal of internally deposited plutonium in human beings. Mated C57BL/Do female mice were given five daily injections of 720–2,880 μmol/kg Ca‐DTPA during early, mid, or late gestation. Damage probably occurred as a result of the depletion by Ca‐DTPA of zinc and manganese, trace elements essential to growth and development. By extension, it seems likely that Ca‐DTPA could damage human fetuses. A much safer chelate, Zn‐DTPA, is recommended for the treatment of accidental plutonium contamination.