bluuebunny/crossref_metadata_2025_split huggingface dataset:
Studies of the development of congenital anomalies in embryos of riboflavin‐deficient, galactoflavin fed rats. I. Growth and embryologic pathology
Authors: Shepard Thomas H. , Lemire R. J. , Aksu O. , Mackler Bruce 
Published: June 2005

AbstractEmbryos from maternal rats maintained on a riboflavin‐deficient, galactoflavin‐augmented diet were compared by gross and histologic examinations with normal controls. On day 11 of gestation no differences were noted between control and treated embryos; on days 12 and 13 the treated embryos were smaller in overall size; and on day 14 the rate of differentiation of tissues of the treated embryos was delayed.The embryonic mortality occurred between day 11 and day 15. Serial sections of day‐14 treated embryos consistently contained extensive areas of necrosis in the mesoblast of the extremities and first branchial arch. A less frequent but similar lesion was found in the central nervous systems in two of four treated embryos examined on day 14. The pathologic lesion resembles the normal cell death which is part of the sculpturing process of developing extremities, but was of much greater magnitude. In addition, studies of sections of the extremities of the treated day‐14 embryos demonstrated a reduction in the number of cellular mitoses. By day 15 the necrosis had disappeared, the mode of clearing presumably being due to macrophage action as evidenced by photographs and by the presence of acid phosphatase‐containing cells in the areas of phagocytosis.In the early stages of mesenchymal condensation the treated specimens evidenced digital fusion but measurements of the relative total volume of mesenchyme were similar in treated and control specimens.Histochemical studies of the treated embryos but not the placentas or maternal tissues demonstrated an overall decrease in the reactions for succinic dehydrogenase from day 12 to day 17. Levels of malic and lactic dehydrogenases and alkaline and acid phosphatases were not decreased in the treated embryos when measured histochemically.
Failure of muscle relaxants to produce cleft palate in mice
Authors: Jacobs Richard M. 
Published: June 2005

AbstractThis study was designed to examine the validity of the theory that descent of the tongue, which is presumably induced by fetal muscular movements, is essential for normal closure of the secondary palate in mice. Nulliparous CD1 mice were given the following “muscle‐paralyzing” agents on day 13° of gestation, i.e., 1 day before the onset of the critical period of palate closure: d‐tubocurarine chloride, gallamine triethiodide (Flaxedil), phenobarbital sodium, chlorphenesin carbamate (Maolate), and ethyl ether. The full paralytical effect of each drug was maintained for 42 hours, i.e., until day 15 1/3 of gestation, by means of subsequent fractional doses. Various combinations of barbiturates, anesthetics, and muscle relaxants were also employed. All litters were recovered by laparotomy on day 15° of gestation. The presence of fetuses that were flaccid, limp, apneic, and unresponsive to stimulation was accepted as evidence of transplacental passage of the employed compounds. No cleft palates were found in 656 recovered fetuses. This may be viewed as an indication that muscular activity — either spontaneous or reflexogenic — is not essential for normal closure of the secondary palate in mice.
Fetal infections of hamsters, rats, and mice induced with the minute virus of mice (MVM)
Authors: Kilham Lawrence , Margolis George 
Published: June 2005

AbstractTransplacental infections with MVM were studied in hamsters, rats, and mice. The most striking infections were in hamsters in which infected fetuses developed high titers of virus, then died, and were resorbed. Only a few fetuses out of each litter became infected, the majority remaining alive, well, and free of infection. The situation in pregnant mice, which are natural hosts of this agent, was different. In them parenteral inoculations produced no discernible effects on either mother or fetuses. But infected fetuses with high titers of virus were recovered from other females at term. In neither hamsters nor mice were instances found of placental infection unaccompanied by fetal infection. Why only a small percent of inoculated pregnant mice developed transplacental infections was not clear. Rats free of immunity and hence susceptible to parenteral inoculations were not found. Intrafetal inoculations of rats revealed, however, that MVM can proliferate in fetuses and then persist for weeks following birh without inducing detectable illness. Histologic studies revealed sparse but characteristic intranuclear inclusions in some animals but it was evident in others that MVM can be present in substantial titers in an absence of apparent histologic change. After direct inoculation of some rat and hamster fetuses generalized severe disease resulted, with replicating tissues being the major viral targets, as has been previously observed in infections with other intrauterine parvoviruses. Here large infectious doses were thought to be responsible for the special effects observed.
The effects of trypan blue on the blood pressure of rat embryos
Authors: Grabowski Casimer T. , Tsai Enoch N. C. , Chernoff Neil 
Published: June 2005

AbstractThe mean ventricular blood pressure (MVBP) of 141 control rat embryos and 164 embryos exposed to trypan blue was measured at 13.5, 14.5, 17.5, and 18.5 days of gestation. The mean pressure in the controls ranged from 19.7 mm water at 13.5 days to 62.7 mm at 18.5 days. The mean pressure of the treated embryos was the same as that of the controls at 13.5 days but about 10 mm lower at all other ages. The range of variation was much greater in experimental embryos than in controls. Many extremely low pressures were recorded in the treated embryos. The pressure differences between control and treated embryos were not due to any differences in rate of heart beat. Since the morphogenesis of the heart and major blood vessels is not completed until day 15.5, and because abnormal pressure and flow patterns can affect cardiovascular development, the abnormal pressures in the 13.5‐ and 14.5‐day groups possibly contribute to the high rate of cardiovascular anomalies induced by trypan blue. The abnormal pressures in the older age group are probably reflections of this heart damage.
The teratogenic response of mouse embryos to 5‐bromodeoxyuridine
Authors: Skalko Richard G. , Packard David S. , Schwendimann Robert N. , Raggio John F. 
Published: June 2005

AbstractPregnant ICR mice were administered single intraperitoneal injections of 300, 400, or 500 mg/kg of the thymidine analogue 5‐bromodeoxyuridine during the period of major organogenesis (days 7–11, Witschi stages 12–25). All dosages were teratogenic. The spectrum of malformations present on day 18 followed a definite stage‐dependency. Exencephaly with associated micrognathia and open eyelid were produced only by treatment during the time the anterior neuropore is open (days 7 and 8) with a peak on day 7. Polydactyly was produced by treatment on days 7 through 10 with a peak on day 9; while cleft palate occurred after treatment on days 9 through 11 with a peak on day 10. Experiments with 3H‐BUDR demonstrated that label appeared in the DNA of embryos and maternal liver at a time when the embryo is susceptible to the teratogenic action of BUDR.
Workshop on monitoring of human mutagenesis
Authors: Sutton H. E. 
Published: June 2005

AbstractOn November 7–8, 1969 a workshop was held in Bethesda, Maryland for the purpose of considering methods of monitoring human populations for environmentally induced mutations. This workshop, sponsored by the National Institute of Environmental Health Sciences, had as participants Drs. Heinz W. Berendes, Barton Childs, Edward M. Cohart, James F. Crow, John H. Edwards, George B. Hutchison, Marvin Legator, Brian MacMahon, Robert W. Miller, James V. Neel, Margery W. Shaw, H. Eldon Sutton (Chairman), and Niel Wald. In addition there were a number of observers from interested government agencies. Members of the workshop considered the various possibilities for systems of monitoring, including, where possible, an estimate of costs as well as scientific benefits.This report was submitted by members of the workshop to Dr. Paul Kotin, Director of the National Institute of Environmental Health Sciences, and does not represent official policy of that Institute. It is presented here because of the general interest in population monitoring for mutations as well as for other effects.
Techniques for prenatal neurosurgical operations on rat fetuses and for obtaining postnatal survivors
Authors: Demyer William , Baird Irene 
Published: June 2005

AbstractPostnatal survivors were obtained after intrauterine neurosurgical lesions were made in fetal rats on the 14th–19th days of gestation. The operations included destruction of a hemispheric wall, unilateral destruction of a rhombic lip or of the nuclei gracilis and cuneatus, spinal cord transection, septal destruction, and optic enucleation. Of 1047 animals subjected to various neurosurgical operations 24% were recovered alive at term. A significant cause of fetal mortality and morbidity was drainage of amniotic fluid. In operations done before the 16th day of gestation, loss of fluid causes cleft palate in approximately 50% of the fetuses born alive. Animals with cleft palate die within hours of birth because they cannot nurse. Postnatal survivability of fetuses subjected to operations can be improved in several ways. Rat mothers vary greatly in handling and nursing their offspring and in their tendency to cannibalization. The experimenter can identify tolerant mothers, and they can be used to produce several litters of operated fetuses. Operations can be planned so that several operated and unoperated females deliver on the same day, so that when some operated females fail to deliver spontaneously many fetuses can still be recovered alive at cesarean section and cross‐fostered to unoperated mothers.
Cysts in cultured fetal rat kidneys
Authors: Monie I. W. , Morgan J. R. 
Published: June 2005

AbstractThe formation of cysts has been studied in kidneys removed from day‐15 and day‐18 rat fetuses and cultured in a mixture of medium 199 (Morgan et al., '50) for periods of up to 15 days. Gas phases of 95% O2 and 5% CO2, and 95% air and 5% CO2, were employed, the latter being considered more satisfactory. In day‐15 kidneys cysts formed from the ampullary portions of the collecting tubules after 2 days whereas cysts derived from nephrons were not seen until 9 days of culturing. The latter arose from developing juxtamedullary nephrons. In day‐18 kidneys cysts from collecting tubules and nephrons were both present after 3 days of culturing. The latter, in this instance, originated mostly in immature midcortical nephrons, the juxtamedullary nephrons having undergone rapid degeneration. The tubular portion of the nephron seemed to be the primary site of dilatation. Under culture conditions cysts of nephrons thus formed from immature actively developing nephrons and not from those that were mature. Cysts associated with collecting tubules arose from the ampullary (terminal) portions of the latter in both day‐15 and day‐18 cultured kidneys. The study of cultured mammalian fetal kidneys can provide information on the nature and genesis of renal cysts. It is possible that the same technique also may be helpful for examining the effects of teratogens directly on the kidney.
Ultrastructural changes in rat palatal epithelium after β‐aminopropionitrile
Authors: Mato M. , Uchiyama Y. , Aikawa E. , Smiley G. R. 
Published: June 2005

Abstractβ‐Aminopropionitrile (BAPN) retarded or suppressed epithelial changes in the medial edge of the palatal process in later stages of gestation in rats. Programmed cell death did not follow the usual pattern, and only a few lysosomes were observed on day 18 of gestation. The sensitivity of the medial epithelium to BAPN appeared to be different in various areas of the palatal epithelium; the epithelium on the anterior region of the palatal process was hypertrophied and keratinized, while posteriorly the medial or neighboring epithelium was very thin and, in neonatal rats, the covering was absent. A basal lamina was distinct in the anterior region and indistinct or fragmented posteriorly. Collagen fibers did not develop adjacent to the basal lamina, and an amorphous material was scattered throughout the mesenchymal tissue. These findings suggest that BAPN decreases the “connecting capacity” between mesenchyme and epithelium, and results in a modification of epithelial changes.
Teratologic evaluation of imipramine hydrochloride in bonnet (Macaca radiata) and rhesus monkeys (Macaca mulatta)
Authors: Hendrickx Andrew G. 
Published: June 2005

AbstractImipramine hydrochloride was administered orally twice daily to 18 bonnet and 3 rhesus monkeys between days 23 and 45 of pregnancy for 1–3 or 18–22 days at 1, 2, and 10 times the recommended human dose. No teratologic changes were observed, although signs of maternal toxicity occurred at the high dose level, and the abortion rate was higher than in controls.
Nonteratogenicity of captan in beagles
Authors: Kennedy Gerald L. , Fancher Otis E. , Calandra J. C. 
Published: June 2005

AbstractThirty and 60 mg/kg captan, administered in the diet during the entire gestation period or during gestation and an 8‐week lactation period, caused no adverse effects in either mothers or progeny, and captan is thus judged to be nonteratogenic in beagles.
Comparison of the teratogenic effects of mustine hydrochloride in rats and ferrets. The value of the ferret as an experimental animal in teratology
Authors: Beck F. , SchöN H. , Mould G. , Swidzinska P. , Curry S. , Grauwiler J. 
Published: June 2005

AbstractThe teratogenic effects on the offspring of ferrets given single sc injections of mustine hydrochloride on various days of gestation is described and compared with a smaller series of rats treated at similar stages of embryonic development. Distinct qualitative differences in the teratogenic responses of the 2 species were demonstrated. The predominant defects in ferrets were anophthalmia produced during early gastrulation, and tail abnormalities produced at the head‐process stage; whereas in rats the major deformities were limb defects and cleft palate and these resulted from treatment at the stage of the paddleshaped forelimb. The advantages of the ferret as an additional species for teratogenicity studies is discussed and methods of providing a continuously breeding colony required for such studies are described.
Accessory Spleens in domestic rabbits (Oryctolagus cuniculus). II. Increased frequency in hematological diseases and experimental induction with phenylhydrazine
Authors: Wkisbroth S. H. , Fox R. R. , Scher S. , Crary D. D. 
Published: June 2005

AbstractAnalysis of several inbred strains of rabbits with high (30–50%) frequencies of accessory spleens revealed that hereditary hematological diseases, autoimmune hemolytic anemia and lymphosarcoma, occurred in some of them. Twenty‐one per cent of individuals in these strains, though phenotypically normal, had globulin‐coated (Coombs'‐positive) erythrocytes. These findings supported observations of increased frequency of accessory spleens in human beings with similar diseases (e.g., autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, “secondary hypersplenism,” Gaucher's disease, hereditary spherocytosis, etc.) and suggested that accessory spleens represent physiological responses to demand for phagocytic capacity provided by the reticuloendothelial system in the spleen, rather than as passive developmental anomalies. This hypothesis predicted that simulation of the basic defect might yield a laboratory model for the induction and study of accessory spleens in rabbits. Phenylhydrazine was used for this purpose and it was shown that the frequency of accessory spleens in 80 rabbits so treated was 45%. Most of these accessories appeared to arise de novo because pretreatment examination in situ by laparotomy revealed a naturally occurring frequency of about 7.5%. These results supported, and provide a basis for, observations by surgeons that subsequent to an initial splenectomy, during which spleniculi were noted to be absent, recurrent indications for splenectomy would later reveal functional accessory spleens. No evidence was found to relate anemia, per se, or cardiovascular anomalies to the increased frequency of accessory spleens in rabbits. It was suggested that heritable factors limit the upward expression of accessory spleens in “normal” populations, as well as during the course of certain diseases and of phenylhydrazine treatment.
Quantitative assessment of effects on fetal rat eyes of fixative and of time postmortem at fixation
Authors: Barash Beverly A. , Shepard Thomas H. 
Published: June 2005

AbstractNumbers of mitotic figures present in parasagittal sections of lens capsules of day‐20 fetal rat eyes and comparison of relative lens volume provided a quantitative basis for comparing tissues fixed in neutral buffered formalin and Bouin's and Lillie's fluids. The number of mitotic figures at 1 or 6 h postmortem was significantly higher in Bouin's and Lillie's‐fixed material than in that fixed in formalin. The estimated volume of the tissue fixed in Bouin's was significantly greater than that of lenses in the other 2 fixatives. In addition the overall appearance of the sectioned lens was examined in an effort to evaluate possible artifacts, especially those that might be interpreted as cataracts. Excessive shrinkage and fragmentation of formalin‐fixed lenses was observed.
Cervical dislocation of the cerebellum in children with meningomyelocele
Authors: Variend S. , Emery John L. 
Published: June 2005

AbstractIn a study of 100 cerebellums from children dying with meningomyelocele, the lobular pattern of the dislocated segment was identified and classified. There was a graded variation in the degree of cerebellar deformity ranging from complete absence of cerebellar tissue in the upper cervical canal to one in which the upper cerebellar lobules were displaced through the foramen magnum. Within this range there were 2 instances in which the cerebellar defect conformed to that found in the Chiari type 1 deformity, consisting of prolapse of tonsillar tissue only. During fetal life the lobular relation in the caudal aspect of the cerebellum undergoes considerable change and it is likely that the type of deformity present in the cervical canal is closely related to the stage of cerebellar development at which the alteration in growth has its inception. The evidence presented argues against the defect being of a primary developmental nature. The terms “Chiari type 1 deformity” and “Arnold‐Chiari malformation” have outlived their usefulness and future descriptions of the cerebellum in children with hindbrain deformities should indicate the shape of the lobules and precise ones involved in the herniation.
Influence of coxsackievirus B infections on fetal growth in mice
Authors: Lansdown A. B. G. 
Published: June 2005

AbstractCoxsackieviruses B1, B3, B4, and B5 injected into TO outbred mice on the 8th day of pregnancy resulted in increased fetal wastage and growth retardation. Coxsackievirus B2 caused increased fetal wastage, whereas Coxsackievirus B6 exhibited no fetal effects. Pregnant animals injected with viruses causing fetal growth impairment ate more food than controls yet did not increase their body weight as much as control animals. Autopsy and pathological findings of advanced destruction of pancreatic exocrine‐tissue and hepatic‐cell vacuolation suggest that the animals were subject to a dietary defect resulting from pancreatic exocrine insufficiency. Fetal growth impairment in mice due to infection with certain Coxsackieviruses of the B group appears to be largely due to a virus‐induced reduction in the state of maternal health. However, since some of these viruses have been shown to pass transplacentally, further studies are necessary to show whether the viruses may also exert a direct effect on fetal tissues.
Concerning so‐called sexual dimorphism in acetazolamide‐induced dysmelia of rats
Authors: Vickers T. H. 
Published: June 2005

AbstractExamination, including gonadal sexing, of Sprague‐Dawley‐derived rats with acetazolamide‐induced dysmelia did not reveal deformity in significantly more females than males. The attributes considered were frequency of defects, prevalence of bilateral lesions, number of litters in which both sexes were present but only 1 was malformed, and severity of anomalies as assessed by the number of residual digits in malformed paws. Unlike the morphological pattern of the dysmelia, which seems stereotyped among the sexes in mice and rats, sex‐determined variation in its severity is not a constant feature of the limb lesions induced by acetazolamide in rats.
The effects of medroxyprogesterone acetate on the maintenance of pregnancy in ovariectomized rats and rabbits
Authors: Bruce N. W. , Bartholomeusz R. K. 
Published: June 2005

AbstractFetal survival, malformation rate, and fetal and placental weights were examined near term in control rabbits, rabbits treated on day 6 with 5 mg of medroxyprogesterone acetate (MPA), a long acting progestin, and rabbits treated with 5 mg of MPA on day 6 and ovariectomized on day 7. MPA alone had no apparent effect on fetal or placental development but MPA plus ovariectomy increased fetal weight by 19% and placental weight by 60%. Fetal and placental development were examined near term in rats given similar treatments. One milligram of MPA administered alone on day 7 had no apparent effect. However, in rats given 1 mg of MPA on day 6 and ovariectomized on day 7 no fetuses survived. In rats given 1 mg of MPA on day 11 and ovariectomized on day 12 only 4.7% of the fetuses survived and all were pressure malformed. In rats given 1 mg of MPA on day 11, ovariectomized on day 12, and supplemented daily with 0.5 μg of estradiol benzoate thereafter, 40% of the fetuses survived and none was malformed, but fetal weights were 22% and placental weights 15% below those of the controls. The underlying problem in the ovariectomized rats supplemented with progestins alone appeared to be failure of myometrial growth. These results highlight the species differences in steroid hormone requirements for fetal, placental, and myometrial development during pregnancy.
Down syndrome in british columbia, 1952‒73: Incidence and mean maternal age
Authors: Lowry R. B. , Jones D. C. , Renwick D. H. G. , Trimble B. K. 
Published: June 2005

AbstractRecords of children with Down syndrome (DS) at the BC Health Surveillance Registry were linked to their Birth Registrations to derive maternal ages. Incidence and maternal‐age specific rates were calculated for 1952‒73. Mean maternal age has declined both for normal and DS children, the latter to a marked degree, so that in 1972‒73 80% were horn to women under 35 years. Using maternal age of 40 and over as an indication for amniocentesis would only detect 10% of DS children. The crude incidence rate (mean 1.28/1000 livebirths) has not changed appreciably over the study period except for 1969 in which a statistically significant peak occurred. The standardized rate showed an increasing trend but it is not clear whether this was a true biological increase or resulted from better ascertainment.