摘要:

AbstractNasolabial morphogenesis in Long‐Evans rats was studied both antenatally and postnatally. Microscopically, the facial processes corresponded to areas where mesenchyme had condensed to form growth centers. Teratogens such as methyl salicylate, trypan blue, and 9‐methyl PGA when administered to pregnant rats principally caused underdevelopment of the maxillary processes and failure of mergence of the nasomedial processes in the young so that a variety of clefts resulted. In addition, some experimental embryos showed shallow grooving of the maxillary process, which corresponded with the location of maxillary cleft, and abnormality occasionally seen at a later stage in man and other anim

ISSN:0040-3709    

DOI:10.1002/tera.1420020102

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1969

数据来源: WILEY

摘要:

AbstractThe cartilage of long bones in newborn achondroplastic (ac/ac) dwarf rabbits was compared with that of phenotypically normal littermates using histologic, histochemical, and electron‐microscopic procedures. The dwarf cartilages contained (1) dead chondrocytes (nuclear pyknosis and absence of surrounding moat) distributed with increasing frequency from the periphery to the center of the resting cartilage (littermate controls showed far fewer and a random distribution of dead chondrocytes); (2) fewer chondrocytes in the isogenous groups or capsules of central portion of the metaphyseal growth plate compared to controls; and (3) less cartilage matrix. Based on these observations it is suggested that a metabolic defect may become expressed specifically in achondroplastic cartilage cells when they are isolated from their vascular suppl

ISSN:0040-3709    

DOI:10.1002/tera.1420020103

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1969

数据来源: WILEY

摘要:

AbstractSingle intraperitoneal injections ofN‐isopropyl‐α‐(2‐methylhydrazino)‐p‐toluamide hydrochloride (procarbazine) at doses ranging from 5–550 mg/kg were given to pregnant rats on the fifth to twelfth, fourteenth, and seventeenth days of gestation. Malformations were seen in twenty‐first‐day fetuses exposed to doses that were slightly higher than one‐half (250 mg/kg on 17th day) to one forty‐fifth (12 mg/kg on 12th day) the single dose that was lethal to females (550 mg/kg) when they were treated once on the fifth, sixth, ninth to twelfth, fourteenth, or seventeenth day of gestation. Tail and appendicular defects were observed after treatment on all eight days, injury to the brain only after that on the ninth day, facial clefts on the ninth or tenth day, and cleft palate and shortened jaws on the sixth, ninth, twelfth, fourteenth, and seventeenth days. Malformations were not seen with any of the doses used on the seventh or eighth day of gestation. Attempts to protect the twelfth‐day fetus against the teratogenic effects of 100 mg/kg of procarbazine by administration of various amounts of L‐methionine were

ISSN:0040-3709    

DOI:10.1002/tera.1420020104

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1969

数据来源: WILEY

摘要:

AbstractRat fetuses were subjected to amniocentesis on days 14.5 to 16.5 of gestation, and the mothers were sacrificed on day 21.5 to ascertain the condition of the fetuses.Amniocentesis of day‐14.5, 15.5, or 16.5 rat fetuses resulted in mortality and malformations whose rates were age‐dependent. Amniocentesis on day 14.5 resulted in nearly 100% mortality, while on day 16.5 the mortality rate was only 26%.Malformations, like mortality, were more frequent after amniocentesis in younger fetuses. Cleft palate occurred only in day‐15.5 animals, but otherwise the malformations after amniocentesis on days 15.5 and 16.5 were similar in type. Compared to controls the fetuses subjected to amniocentesis were smaller and had peculiar, thickened trunks and necks. They had short, stiff extremities with clubfeet, primitive digits or adactyly, scoliotic tails, microstomia, and short umbilical cords. None of the control fetuses had any of these features.The mechanism of the malformations is postulated to be oligohydramnios and intrauterine immob

ISSN:0040-3709    

DOI:10.1002/tera.1420020105

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1969

数据来源: WILEY

摘要:

AbstractA number of viruses are capable of producing intrauterine infection and damage. Both rubella and cytomegalovirus may cause malformations. For rubella the most frequent defects are those involving the heart, eyes, brain, and ears. With cytomegalovirus, children may be microcephalic, small, and mentally retarded. The mechanism of teratogenesis for rubella is apparently related to the direct infection of the virus in certain tissues of the developing fetus. Indirect effects may also be caused by vascular occlusion due to damage of blood vessels. Studies of rubella in experimental animals have not been particularly successful. Isolated reports have suggested that congenital damage can be produced in monkeys and rats. Further studies, however, are necessary.A number of “model systems” are available for the study of viruses in experimental animals. It is now possible to utilize basic guidelines in consideration of experimental teratogenesis in these systems. These guidelines include: 1. Infection should be produced in the adult and fetus or newborn animal. 2. In most cases the virus used should be low passage, well adapted to the animal, and preferably passaged in the living animal. 3. Several different intervals during gestation should be studied, including the inoculation of newborn young. Several dosages and routes should be tried. 4. Indirect effects on the mother or infant, environmental factors, mating patterns, and genetic background variables should be considered. 5. The effects should be prevented by specific neutralization of the vi

ISSN:0040-3709    

DOI:10.1002/tera.1420020106

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1969

数据来源: WILEY

摘要:

AbstractPreimplantation mouse embryos (ICR strain) were removed from the oviducts of pregnant females at 55, 60, and 65 hours after ovulation and cultured in a medium containing inorganic salts, horse serum, and sodium pyruvate. Experimental embryos were exposed to a range of dosages of actinomycin D (10−1–10−5μg/ml) and were observed at 24 and 48 hours after the initiation of the experiment. The results obtained were independent of embryonic stage but demonstrated a distinct dose‐dependency. Exposure to 10−1μg/ml was incompatible with further development. Embryos exposed to 10−2μg/ml formed blastocysts (24 hours) at a rate lower than corresponding controls and all were degenerated at the termination of the experiment (48 hours). Blastocyst formation by embryos exposed to 10−3μg/ml occurred at a rate that was equal to or exceeded control values, but a significant percentage of these blastocysts were degenerated after 48 hours in vitro. Embryos exposed to the lower dosages (10−4and 10−5μg/ml) did not differ from corresponding control embryos with respect to the percentage of blastocysts observed at 24 and 48 hours.These results suggest that actinomycin D affects two developmental processes: blastocyst formation and blastocyst survival or differentiation. The latter of these is more sensitive to the developmental effects of the agent and is at least circumstantially related to the early appearance of the nucl

ISSN:0040-3709    

DOI:10.1002/tera.1420020107

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1969

数据来源: WILEY

摘要:

AbstractA technique was developed for the intrauterine application of teratogens to study fetal rat malformations produced by benzhydrylpiperazine compounds. Millipore filters (0.2 × 0.2 cm) impregnated with 50 μg chlorcyclizine HCl, 50 μg norchlorcyclizine HCl, or HCl alone were inserted through the uterine wall and placed on either the intact amniotic sac (over the fetus) or the placenta. Filters containing norchlorcyclizine implanted on the amniotic sac on day 13 or 14 produced 30% cleft palate, while chlorcyclizine filters produced only 3% cleft palate. Limb anomalies were also seen after norchlorcyclizine‐ or chlorcyclizine‐filter insertion. The optimal time of producing these malformations was day 13 or 14 of gestation. The agents exerted localized teratogenic activity since insertion of norchlorcyclizine filters over the head area of day‐14 fetuses resulted in 42% cleft palate, while those placed over the hindlimb produced only 11% cleft palate but 55% hindlimb malformations. Control HCl filters inserted over the fetus and norchlorcyclizine filters placed on the placenta produced no malfo

ISSN:0040-3709    

DOI:10.1002/tera.1420020108

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1969

数据来源: WILEY

摘要:

AbstractExposure of chick embryos to moderate hypoxia (6–10% O2for 4–6 hours) induces a marked blood‐volume increase. This treatment also precipitates hemorrhage that can cause death or malformation or both when localized near rapidly developing structures. To determine whether the hypoxia‐induced hypervolemia can raise embryonic blood pressure to a hemorrhage level, the mean ventricular blood pressure (MVBP) of 587 embryos was measured before, during, and after treatment. The mean MVBP of 3‐day embryos rose from 11.1 mm water to 14.7 mm during the first two hours of hypoxia, dropped slowly during the rest of treatment, then increased again after exposure to air. The highest mean values (16.4 mm) were obtained two hours after treatment, coinciding with the time of maximum hemorrhage. The range of MVBP at that time was wide (6.0–27.0 mm) and in many embryos was twice as high as normal. The MVBP gradually returned to normal 2–13 hours after treatment. Maximum increases in the MVBP of 4 to 5‐day embryos also occurred during the second hour after treatment, but recovery after that was faster than at three days.In a parallel experiment hypervolemia was induced by sequential injection of saline into the ventricles of 3‐day embryos, in between pressure measurements. The MVBP rose slowly up to 30 mm water. Bleeding usually began at pressures of 18 mm. Hypervolemia induced by hypoxia appears to be responsible for the blood‐pressure increases and the development of teratogenically i

ISSN:0040-3709    

DOI:10.1002/tera.1420020109

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1969

数据来源: WILEY

摘要:

AbstractAs is true for laboratory or clinical research, epidemiology can either generate or test hypotheses about the origins of disease. In so doing with respect to cardiac anomalies, rubella virus was identified as an environmental cause and the role of genetics has been clarified. Microscopically visible chromosomal aberrations have been related to high rates of diverse cardiac defects in Turner's and autosomaltrisomy syndromes. Submicroscopic genetic defects may also produce heart anomalies, as in Marfan's syndrome. The role of inheritance in the production of cardiac malformations in general, however, appears to be small as indicated by studies of twins (only 1 of 6 series revealed an elevated concordance rate in identical pairs) or by studies of the effect of consanguinity. Yet a wide variety of congenital heart disease has been repeatedly found to occur excessively in families. Future research must evaluate whether these occurrences are determined pre‐ or postzygotically. By so doing the origins of sporadic cases may be elicited. The possibilities include submicroscopic chromosomal abnormalities, chemical or microbial agents that interfere with normal embryonic development, and combinations of these factors. Through the use of existing data resources epidemiologic research can help to identify the influence of each. Although computer technology has its value, etiologic insight, which can be tested by the epidemiologic method, seems more likely to come from observations made by physicians at the bedsid

ISSN:0040-3709    

DOI:10.1002/tera.1420020110

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1969

数据来源: WILEY

ISSN:0040-3709    

DOI:10.1002/tera.1420020101

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1969

数据来源: WILEY