ISSN:0040-3709    

DOI:10.1002/tera.1420230215

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

年代:1981

数据来源: WILEY

摘要:

AbstractAnatomical features are described in a case of cephalothoracopagus female twins with laterally fused heads. There was a single foregut, shared equally by the two individuals. The tracheae, lungs, hearts, livers, and gallbladders were also shared by the two individuals. They were located in the anterior and posterior regions of the joined bodies. These peculiarities occur in other cases of Cephalothoracopagus twinning reported in the literature, and may have been caused by spatial problems in the developing twin embryos. In particular, each heart is considered to be a composite organ, formed by tissue from both individuals. The occipital region of the skull was double, but the remainder of the cranium was single. The oral cavity was divided in two by a midline mandibular body thought to represent the fused medial portions of two mandibles. Each compartment so formed contained a tongue. This midline body is considered responsible for a cleft lip and palate. Finally, we propose that anencephaly in this and other cases of laterally fused heads is associated with mechanical difficulty in closing the rostral neuropore.

ISSN:0040-3709    

DOI:10.1002/tera.1420230202

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

年代:1981

数据来源: WILEY

摘要:

AbstractPrevention of congenital malformations is recognized as the ultimate goal of teratology, a goal that has not yet been reached despite much progress in the description, experimental production, and treatment of birth defects. In addition to quests for the causes of congenital malformations and the removal of these causes, indirect preventive methods must be sought that could aid in eliminating these malformations as sources of children's morbidity and mortality.

ISSN:0040-3709    

DOI:10.1002/tera.1420230203

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

年代:1981

数据来源: WILEY

摘要:

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 p

ISSN:0040-3709    

DOI:10.1002/tera.1420230204

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

年代:1981

数据来源: WILEY

摘要:

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 dr

ISSN:0040-3709    

DOI:10.1002/tera.1420230205

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

年代:1981

数据来源: WILEY

摘要:

AbstractPregnant rats were intubated twice daily throughout gestation with the equivalent of 3 gm/kg of alcohol in the form of either beer, wine, whiskey, or 95% ethanol. Control animals received vehicle. All animals were pair‐fed to those receiving ethanol. Offspring were removed from their biological mothers immediately following birth and were nursed by nondrug‐treated mothers. Animals in each of the four alcohol‐treated groups weighed significantly less than the animals in the control group at birth and at 22 days of age and also performed significantly worse on a Rotarod at 17 days; differences among the four alcohol‐treated groups were not significant for any of these measures. Results suggest that congeners present in these alcohol beverages do not potentiate the effects of alcohol on embryonic/fetal development in rats administered this alcoh

ISSN:0040-3709    

DOI:10.1002/tera.1420230206

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

年代:1981

数据来源: WILEY

摘要:

AbstractPregnant rats received intraperitoneal injections of cytochalasin D (CD) on gestational days 7–11. Doses of 400 μg/kg were only minimally and nonsig‐nificantly teratogenic, leading to 2 exencephalic fetuses among the 111 fetuses delivered. By contrast, embryos exposed to CD in vitro on day 10 showed significant frequencies of neural tube abnormalities when exposed to CD concentrations at or above 3.1ng/ml. These embryos also exhibited significantly decreased protein, somite counts, and crown‐rump lengths.In order to understand this apparent discrepancy between the teratogenicity of CD in vivo and in vitro we performed experiments to determine whether drug metabolism could inhibit the teratogenicity in vitro. Male rats were pretreated with a mixture of polychlorinated biphenyls as cytochrome P‐450 inducers, and their livers were used to prepare a microsome‐rich fraction (S‐9). This S‐9 fraction, plus a source of reducing equivalents (NADPH), significantly inhibited the teratogenicity of CD. The teratogenicity was restored by the omission of NADPH, and was partially restored with the addition of carbon monoxide.These results led us to conclude that the teratogenic effect of CD can be inhibited by drug metabolism in vitro; additionally, it is likely that some or all of this drug metabolism may depend on cytochrome P‐450. We further speculate that CD may be inactivated in vivo by these same systems, explaining the discrepancy between the teratogenicity of CD in v

ISSN:0040-3709    

DOI:10.1002/tera.1420230207

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

年代:1981

数据来源: WILEY

摘要:

AbstractPregnant ICR/JCL mice were given orally 0.02, 0.2, or 2.0 mg/ kg body weight/day of ethinyl estradiol in olive oil or vehicle alone on day 11 through day 17 of pregnancy. Pregnant mice of another group received a single oral dose of ethinyl estradiol on day 8 or day 11 of pregnancy. A lethal effect on fetuses of both groups with single and continuous exposure to ethinyl estradiol was observed in a dose‐response relationship. Growth suppression of fetuses was only found at term in a dose‐response relationship following continuous exposure to ethinyl estradiol. Hypertrophic nipples were seen in 42% of surviving female fetuses prenatally exposed to 2.0 mg/kg of ethinyl estradiol singly on day 11 of gestation. There was not an increase in other congenital malformations in any of the treated groups. These findings indicate that administered ethinyl estradiol can affect the developing mouse embryo but the embryotoxic doses in the mouse are substantially greater than the usual therapeutic or contraceptive doses in the hu

ISSN:0040-3709    

DOI:10.1002/tera.1420230208

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

年代:1981

数据来源: WILEY

摘要:

AbstractA potent inhibitor of thymidylate synthetase, 5–Fluorodeoyxyuridine (FUdR), produced dose‐ and stage‐dependent skeletal defects in embryos of mice injected during early development (10th‐13th day). The dose of 25 mg/kg was teratogenic producing few resorptions and little reduction in fetal weight. Hindlimbs were much more sensitive to the drug than were the forelimbs and showed dose‐dependent long bone reductions. Specific long bone reductions occurred after treatment on the 11th or 11.5 day and were accompanied by preaxial polydactyly; treatment on the 12th or 12.5 day produced high incidence of ectrodactyly but no long bone reductions. Limbs were insensitive on the 13th day of development and beyond. Limb buds in organ culture demonstrated a direct action of FUdR on undifferentiated mesenchymal cells, incurring what has been previously termed “thymineless” cell death. Dose‐dependent reduction of viable cell number led to a reduction in chondrogenic expression in vitro–more so in the hindlimb than the forelimb. Similar occurrence of cell death was also noted after in utero exposure, and here, it was followed by a process of recovery. The recovery phase was characterized by the formation of a distal synchronized cell population derived from undamaged subridge cells leaving damaged cells at the proximal extent of the subridge zone. Limb segments maintained their temporal sequence of differentiation, and their regulatory capability was related to the time allotted for repopulation of the subridge zone. We propose that a faster growth during early development of the elements of the hindlimb versus analogous ones of the forelimb allows the former less time for regulation–and hence, higher sensitivity to antiproliferative

ISSN:0040-3709    

DOI:10.1002/tera.1420230209

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

年代:1981

数据来源: WILEY

摘要:

AbstractLong‐Evans black‐hooded rats treated via stomach tube with 160,000USP units of retinyl acetate (vitamin A) in 0.5 ml Mazola corn oil on gestational days 15–19 deliver normal‐sized litters with significantly decreased viability. Vitamin A is known to effect the differentiation and to stimulate the growth of epithelial cells. Additionally, lung epithelia undergo marked morphologic and physiologic changes late in gestation. Thus the effects of hypervitaminosis A on developing lung constitute an excellent system for the study of teratogenesis late in gestation.Non‐hilar, right lower‐lobe sections of lungs from the vehicle control and experimental groups, compared via quantitative light microscopy, revealed no significant difference in gross overall histologic appearance on any given day, either in the total number of airways present in the volume of lung sectioned or in the percent area of any individual airway occupied by cells or by lumen. The only significant difference was in the number of cells per square micrometer in that region of an airway occupied by cells. Additionally, there was a significant difference between the control and experimental mitotic indices on gestational days 18 and 19. Thus in the experimental group the number of cells lining the developing airways increases, while the absolute thickness of this cellular layer remains constant. Transmission electron microscopy (TEM) fails to reveal any morphologic differences between control and treated type II pneumatocytes. The increased number of respiratory cells in what otherwise appears to be normal lung may create a diffusion‐perfusion imbalance or other difficulties contributing to the heightened neonatal mortality resulting from teratogen exposure late

ISSN:0040-3709    

DOI:10.1002/tera.1420230210

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

年代:1981

数据来源: WILEY