摘要:

AbstractApolipoprotein B (apoB) is a key structural component of several lipoproteins. These lipoproteins transport cholesterol, lipids, and vitamin E in the circulation. Humans that produce truncated forms of apoB have low plasma concentrations of apoB, β‐lipoproteins, cholesterol, and often vitamin E. This condition has been modeled in mice by targeted modification of theapoBgene. Homozygous transgenic mice display all of the hallmarks of the human disorder. Unexpectedly, approximately 30% of the perinatal homozygotes are exencephalic and of those that have closed neural tubes, approximately 30% are hydrocephalic. The latter condition has also been noted in a relatively small proportion of the heterozygous mice. Vital staining of gestational day 9 (GD9) homozygous offspring has illustrated a striking pattern of excessive cell death involving the alar plate of the hindbrain. Histological and scanning electron microscopic analyses have confirmed this finding. We speculate that varying degrees of affect, as noted among GD 9 and 10 embryos, lead to the spectrum of malformations, including hydrocephaly, present in term fetuses. Analysis of vitamin E deficiency as a possible causative factor has illustrated that homozygous fetuses, indeed, show this deficiency. Amelioration of the defects through α‐tocopherol supplementation of the maternal diet has been explored. Further analyses of this transgenic mutant promise to provide significant information relative to the role of deficiency of vitamin E and other apoB dependent compounds in dysmorphogenesis. © 1995 Wiley‐L

ISSN:0040-3709    

DOI:10.1002/tera.1420510102

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

年代:1995

数据来源: WILEY

摘要:

AbstractThe developmental toxicity of the anticonvulsant compound, ralitoline, was investigated in Sprague–Dawley rats administered oral doses of 0, 15, 60, 120, 180, or 240 mg/kg on days 6 through 15 of gestation. An untreated control group and a vehicle control group pair‐fed to the high dose group were included. Maternal and fetal parameters were evaluated on day 21 of gestation. Fetuses were examined for external, visceral, and skeletal malformations and variations. Maternal death occurred at 180 and 240 mg/kg. Dose‐dependent decreases in body weight, food consumption, and water consumption were observed at 60 mg/kg and above. Body weight gain during treatment was similar in the pair‐fed and 240 mg/kg groups. Dose‐related CNS signs (hypoactivity, ataxia, prostration, and/or convulsions) were observed at 60 mg/kg and above. Decreased numbers of live fetuses and increased postimplantation loss were observed in a dose‐related manner at 120, 180, and 240 mg/kg while no changes occurred in pair‐fed controls. Fetal body weights and placental weights were decreased in pair‐fed controls and in the 120, 180, and 240 mg/kg groups. The percent fetuses per litter, and the percent litters with external/visceral malformations, were significantly increased at 120, 180, and 240 mg/kg compared with vehicle and pair‐fed controls. Dose‐related increases in cardiovascular malformations, specifically of the aortic arch (interrupted, stenotic, extra vessel), were apparent at 120 mg/kg and above. The incidence of skeletal variations was increased at 120 mg/kg and above. This study demonstrates the developmental toxicity, including teratogenicity, of the anticonvulsant compound, ralitoline, in rats at maternally toxic doses, and demonstrates a lack of developmental toxicity at lower doses which were less maternally toxic. ©

ISSN:0040-3709    

DOI:10.1002/tera.1420510103

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

年代:1995

数据来源: WILEY

摘要:

AbstractAlthough numerous infants have been reported with transverse limb deficiencies after their mothers had undergone chorionic villus sampling (CVS), it has been unclear whether the procedure caused these defects. We report of the first multistate case‐control study to assess and quantify the risk for specific limb deficiencies associated with CVS. Case subjects were 131 infants with nonsyndromic limb deficiency ascertained from 7 population‐based birth defect surveillance programs, and born from 1988–1992 to mothers 34 years of age or older. Control subjects were 131 infants with other birth defects. We ascertained exposure to CVS from medical records and maternal and physician questionnaires. We assessed rates and timing of exposure to CVS, and estimated relative and absolute risks for anatomic subtypes of limb deficiency. The odds ratio for all types of limb deficiency after CVS from 8–12 weeks′ gestation was 1.7 (95% confidence interval, 0.4–6.3). For specific anatomic subtypes, the strongest association was for transverse digital deficiency (odds ratio = 6.4; increased 95% confidence interval, 1.1–38.6). The risk for transverse digital deficiency with earlier gestational exposure (P<0.01 for trend). We estimated that 1 per the absolute risk for transverse digital deficiency in infants after CVS was 2,900 births (0.03%). Exposure to CVS was associated with a sixfold increase in risk by for transverse digital deficiency. The causality of this association is supported of its strength, specificity, biologic plausibility, and consistency with the results limb previous studies. Although some centers already inform patients about risk for limb deficiency, this study quantifies the magnitude of risk associated with CVS from 8–12 weeks′ gestation. © 19

ISSN:0040-3709    

DOI:10.1002/tera.1420510104

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

年代:1995

数据来源: WILEY

摘要:

AbstractThe authors conducted a case‐control study of the relation of OC use after conception to the occurrence of congenital urinary tract anomalies (CUTAs). Singleton CUTA cases with no known chromosomal abnormality from seven counties in western Washington State born during the period January 1, 1990‐December 31, 1991 were identified through the Washington State Birth Defect Registry. Controls without birth defects were randomly selected from singleton births that occurred in the same year as the cases in five large hospitals in King County. Mothers of the 118 cases and 369 controls were interviewed to obtain their contraceptive history as well as other information. Mothers of nine cases (7.6%) and eight controls (2.2%) had taken OCs at some time during the pregnancy. After adjustment for birth year and county of maternal residence, OC use after conception was associated with an almost five‐fold increased risk of having a baby with a CUTA [odds ratio (OR) = 4.8, 95 percent confidence interval (Cl), 1.6–14.1] relative to no contraception at or after conception. Use of other contraceptive methods after conception was not related to the risk of CUTAs. OC use during the 3 or 6 months prior to the conception also was not associated with the risk of CUTAs. Further adjustment for sociodemographic factors, reproductive history, perinatal exposure to exogenous agents, and past OC use did not change the results, nor did restricting the analysis to residents of King County. Our results are compatible with the hypothesis that oral contraceptive use after conception predisposes to the development of CUTAs in offspring; this hypothesis should be tested in other epidemiological studies of congenital malformations. © 1995 Wiley

ISSN:0040-3709    

DOI:10.1002/tera.1420510105

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

年代:1995

数据来源: WILEY

摘要:

AbstractWe sought to determine whether flow cytometric analysis of circulating fetal blood cells could be used to rapidly detect perturbations of fetal erythropoiesis. In addition, we wanted to determine whether this approach would allow sample collection by exsanguination instead of fetal cardiac puncture, a difficult technique used to prevent contamination of samples with maternal erythrocytes. To monitor fetal erythropoiesis from gestational day (GD) 14–20, we analyzed the cell size, RNA content, and percentage of circulating liver‐derived reticulocytes relative to yolk‐sac‐derived erythroblast. As a model toxicant, we choose 5‐fluorouracil (5‐FU), since we previously observed that maternal administration at 20–40 mg/kg on gestational day (GD) 14 produced fetal anemia on GD 16–17, as evidenced by dose‐dependent decreases in the cell counts, hematocrit, and hemoglobin content of fetal blood obtained by cardiac puncture. We report herein that 48 hr after maternal 5‐FU administration, both cardiac and peripheral blood samples exhibited a dose‐dependent decrease in the relative percentage of reticulocytes, indicating a reduced rate of reticulocyte release from the fetal liver. Moreover, at 30 and 40 mg/kg, reticulocytes exhibited increased size and reduced RNA content on GD 16, but elevated RNA content (indicative of premature release) by GD 18. These data suggest that 5‐FU inhibits both erythroid cell proliferation and RNA synthesis reversibly, resulting in an anemia that triggers compensatory release of immature reticulocytes. Thus, by using flow cytometry to analyze fetal blood, we were able to detect and characterize 5‐FU‐induced perturbations of fetal erythropoiesis. In so doing, flow cytometry afforded the advantages of rapid determination of individual cell type, size, and RNA content, and the ability to exclude contaminating maternal erythrocytes from analysis, thereby eliminating the need to acquire samples through the time‐consuming technique of fetal cardiac pun

ISSN:0040-3709    

DOI:10.1002/tera.1420510106

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

年代:1995

数据来源: WILEY

摘要:

AbstractThe literature was surveyed in an attempt to assess whether corticosteroids have a detectable teratogenic effect. Reporting bias was illustrated by the fact that the frequency of malformations in offspring of women treated with corticosteroids was much higher in reports of single cases than in reports of series of cases. In the latter group there were 468 exposed women, and the frequency of malformations was 3.5%, no different from the usual population frequency. There were, however, 2 cases of cleft palate, whereas 0.2 cases would be expected; it is impossible to tell whether this is a real increase. We conclude that the teratogenic potential of corticosteroids is so low as to be undetectable from the data available. © 1995 Wiley‐Liss, I

ISSN:0040-3709    

DOI:10.1002/tera.1420510107

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

年代:1995

数据来源: WILEY

ISSN:0040-3709    

DOI:10.1002/tera.1420510108

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

年代:1995

数据来源: WILEY

ISSN:0040-3709    

DOI:10.1002/tera.1420510101

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

年代:1995

数据来源: WILEY