Teratology最新文献

{"title":"Pregnancy outcomes after first trimester exposure to phentermine/fenfluramine.","authors":"K. Jones, Kathleen A. Johnson, Lyn M. Dick, R. Felix, K. Kao, C. Chambers","doi":"10.1002/TERA.10023","DOIUrl":"https://doi.org/10.1002/TERA.10023","url":null,"abstract":"BACKGROUND\u0000Fenfluramine was withdrawn from the U.S. market in 1997 because of its association with cardiac-valve abnormalities in adults. The combination of fenfluramine and phentermine had been widely used to promote weight loss, and many women were inadvertently exposed during the first trimester of pregnancy. The possible effect on the developing fetus has not been studied.\u0000\u0000\u0000METHODS\u0000Controlled prospective cohort study comparing 98 women who had taken phentermine/fenfluramine to 233 women who had not, all of whom contacted the California Teratogen Information Service during pregnancy.\u0000\u0000\u0000RESULTS\u0000The proportion of liveborn infants with major structural anomalies was similar in the two groups (3.6% vs. 1.0%, relative risk (RR) 3.59; 95% confidence interval (CI) 0.61, 21.10), as was the proportion of infants with >or=3 minor anomalies (11.7% vs. 7.6%, RR 1.53; 95% CI 0.61, 3.82). Furthermore, no pattern of malformation was identified. There were no significant differences between the groups in spontaneous pregnancy loss (6.1% vs. 8.2%, P = 0.65) or premature delivery (8.6% vs. 7.7%, P = 0.95). Birth weight and head circumference were significantly increased in the exposed group; however, these differences were not associated with anorexiant use itself. The rate of gestational diabetes was significantly increased in pregnant women who took phentermine/fenfluramine during the first trimester of pregnancy.\u0000\u0000\u0000CONCLUSIONS\u0000Although it is not possible from this study to rule out weak to moderate associations, the lack of an increased risk of spontaneous pregnancy loss, and major or minor anomalies in the offspring of women who took phentermine/fenfluramine at the recommended daily dose during the first trimester of pregnancy is reassuring.","PeriodicalId":22211,"journal":{"name":"Teratology","volume":"48 1","pages":"125-30"},"PeriodicalIF":0.0,"publicationDate":"2002-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90967047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered mandibular development precedes the time of palate closure in mice homozygous for disproportionate micromelia: an oral clefting model supporting the Pierre-Robin sequence.","authors":"James E Ricks, Victoria M Ryder, L. Bridgewater, B. Schaalje, R. Seegmiller","doi":"10.1002/TERA.10022","DOIUrl":"https://doi.org/10.1002/TERA.10022","url":null,"abstract":"BACKGROUND\u0000Development of the human craniofacial anatomy involves a number of interrelated, genetically controlled components. The complexity of the interactions between these components suggests that interference with the spaciotemporal interaction of the expanding tongue and elongating Meckel's cartilage correlates with the appearance of cleft palate. Mice homozygous for the semi-dominant Col2a1 mutation Disproportionate micromelia (Dmm), presenting at birth with both cleft palate and micrognathia, provide the opportunity to test the hypothesis that mandibular growth retardation coincides with formation of the secondary palate as predicted from our understanding of the Pierre Robin sequence. The present study was conducted in embryonic day 14 (E14) mice, 1 day before palate closure, to describe the relationship between growth of the lower jaw/tongue complex versus genotype of the embryo.\u0000\u0000\u0000METHODS\u0000Whole heads, isolated from E14.25, E14.5 and E14.75 wild-type and homozygous mutant embryos, were fixed in Bouin's solution, embedded in paraffin, and serially sectioned. Mid-sagittal sections, stained with toluidine blue, were used to estimate growth of both tongue and lower jaw (Meckel's cartilage length) during a 12-hr period preceding palate closure.\u0000\u0000\u0000RESULTS\u0000In control embryos, the largest increase in Meckel's cartilage length occurred between E14.5 and E14.75. Compared to control, the mean Meckel's cartilage length in the mutant was similar at E14.25, but was significantly less at E14.5 and E14.75. Absolute tongue size in control embryos increased linearly during this period of E14.25 to E14.75. Relative to the rapidly growing Meckel's cartilage, however, relative tongue size in control embryos actually decreased over time. Absolute tongue size in the mutant was not significantly different from that of control at any of the embryonic stages examined, however, relative tongue size in the mutant was significantly greater at E14.75 compared to control.\u0000\u0000\u0000CONCLUSION\u0000Mandibular growth retardation, coupled with relative macroglossia in E14 Dmm/Dmm mice, suggests that the concerted development of the palate and lower jaw complex in the mutant is aberrant. Detection of micrognathia and pseudomacroglossia in homozygotes, before the time of palate closure, supports the hypothesis that a relationship exists between growth retardation of Meckel's cartilage and malformation of the secondary palate, as predicted by the Pierre-Robin sequence.","PeriodicalId":22211,"journal":{"name":"Teratology","volume":"29 1","pages":"116-20"},"PeriodicalIF":0.0,"publicationDate":"2002-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83736150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Do platelet-released phospholipids play a role in cardiovascular malformations and heritable coangulopathies?","authors":"D. English","doi":"10.1002/TERA.10026","DOIUrl":"https://doi.org/10.1002/TERA.10026","url":null,"abstract":"","PeriodicalId":22211,"journal":{"name":"Teratology","volume":"63 1","pages":"102-5"},"PeriodicalIF":0.0,"publicationDate":"2002-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91140661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The biology of cardiovascular malformations—At last! Reply to Dr. English","authors":"C. Ferencz","doi":"10.1002/TERA.10027","DOIUrl":"https://doi.org/10.1002/TERA.10027","url":null,"abstract":"","PeriodicalId":22211,"journal":{"name":"Teratology","volume":"54 1","pages":"105-105"},"PeriodicalIF":0.0,"publicationDate":"2002-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75927149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design and development of an Internet registry for congenital heart defects.","authors":"W. Mitri, A. Sandridge, S. Subhani, W. Greer","doi":"10.1002/TERA.10016","DOIUrl":"https://doi.org/10.1002/TERA.10016","url":null,"abstract":"BACKGROUND\u0000Congenital Heart Defects (CHD) are conditions that encompass more than 50 diagnoses and are due to developmental abnormalities early in fetal life. The King Faisal Specialist Hospital and Research Centre in the Kingdom of Saudi Arabia treats approximately 100 new cases per month. We recently developed a new CHD Registry that captures, stores and processes our data via the Internet.\u0000\u0000\u0000METHODS\u0000The Registry was developed using Hypertext Markup Language (HTML), Microsoft Active Server Pages and Microsoft Structured Query Language (SQL).\u0000\u0000\u0000RESULTS\u0000Details of CHD cases are captured in a World Wide Web (WWW) Registry, permitting any browser-enabled PC or Mac to participate fully in all registry functions, including data-entry, viewing, editing, searching, reporting, validating, charting, and exporting data subsets to statistics packages. It includes \"administrative\" features and an active security system. The paper forms have been designed to reflect the \"look and feel\" of the Web pages. Automatic validation procedures are also included.\u0000\u0000\u0000CONCLUSIONS\u0000Our Registry has been in operation for 3 years. It serves 10 PCs and contains more than 3,000 registered cases of CHD. It is the first CHD Registry to be fully functional on the Internet. It is also the first dedicated CHD registry, and the first to routinely report on the full spectrum of CHD diagnoses. The WWW offers several logistical advantages to disease registries, especially those that represent large regions. It also offers the possibility of sharing resources between registries, facilitating the aggregation and analysis of disease data on a world-wide scale. This is useful for rare diseases such as CHD (see http://rc.kfshrc.edu.sa/chdr/demo/).","PeriodicalId":22211,"journal":{"name":"Teratology","volume":"20 1","pages":"78-87"},"PeriodicalIF":0.0,"publicationDate":"2002-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75440181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Priming the search for HOX mutations.","authors":"J. Innis","doi":"10.1002/TERA.10021","DOIUrl":"https://doi.org/10.1002/TERA.10021","url":null,"abstract":"Background: The HOX gene family consists of highly conserved transcription factors that specify the identity of the body segments along the anteroposterior axis of the embryo. Because the phenotypes of mice with targeted disruptions of Hox genes resemble some patterns of human malformations, mutations in HOX genes have been expected to be associated with a significant number of human malformations. Thus far, however, mutations have been documented in only three of the 39 human HOX genes (HOXD13, HOXA13, and HOXA11) partly because current knowledge on the complete coding sequence and genome structure is limited to only 20 of the 39 human HOX genes. Methods: Taking advantage of the human and mouse draft genome sequences, we attempted to characterize the remaining 19 human HOX genes by bioinformatic analysis including phylogenetic footprinting, the probabilistic prediction method, and comparison of genomic sequences with the complete set of the human anonymous cDNA sequences. Results: We were able to determine the full coding sequences of 19 HOX genes and their genome structure and successfully designed a complete set of PCR primers to amplify the entire coding region of each of the 39 HOX genes from genomic DNA. Conclusions: Our results indicate the usefulness of bioinformatic analysis of the draft genome sequences for clinically oriented research projects. It is hoped that the mutation panel provided here will serve as a launch-pad for a new discourse on the genetic basis of human malformations.","PeriodicalId":22211,"journal":{"name":"Teratology","volume":"1 1","pages":"47-9"},"PeriodicalIF":0.0,"publicationDate":"2002-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90132866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of folate supplementation on the risk of spontaneous and induced neural tube defects in Splotch mice.","authors":"L. Gefrides, G. Bennett, R. Finnell","doi":"10.1002/TERA.10019","DOIUrl":"https://doi.org/10.1002/TERA.10019","url":null,"abstract":"BACKGROUND\u0000Neural tube defects (NTDs) are among the most common human congenital malformations. Although clinical investigations have reported that periconceptional folic acid supplementation can reduce the occurrence of these defects, its mechanism remains unknown. Therefore, the murine mutant Splotch, which has a high incidence of spontaneous NTDs, along with the inbred strains SWV and LM/Bc, were used to investigate the relationship between folate and NTDs.\u0000\u0000\u0000METHODS\u0000To investigate whether folates could reduce spontaneous NTDs, heterozygous Splotch dams (+/Sp) were treated with either folate or folinic acid throughout neurulation, gestational day (GD) 6.5 to 10.5. On GD 18.5 the dams were sacrificed and the fetuses examined for any neural tube defects. Subsequently, Sp/+ dams were treated with arsenic while receiving either a folate or folinic acid supplementation. Similar experiments were performed in the LM/Bc and SWV strains.\u0000\u0000\u0000RESULTS\u0000Neither folate nor folinic acid supplements reduced the frequency of spontaneous NTDs in the embryos from Splotch heterozygote crosses. Arsenic increased the frequency of NTDs and embryonic death in the Splotch, LM/Bc and SWV litters and folinic acid failed to ameliorate the teratogenic effect of this metal. A folate supplement given to arsenic-treated dams proved to be maternally lethal in all three strains.\u0000\u0000\u0000CONCLUSIONS\u0000Splotch embryos were not protected from either spontaneous or arsenic-induced NTDs by folinic or folic acid supplementation. Furthermore, folinic acid supplements did not reduce the incidence of arsenic-induced NTDs in either the LM/Bc or SWV litters.","PeriodicalId":22211,"journal":{"name":"Teratology","volume":"5 1","pages":"63-9"},"PeriodicalIF":0.0,"publicationDate":"2002-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75396443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Depletion of Mab21l1 and Mab21l2 messages in mouse embryo arrests axial turning, and impairs notochord and neural tube differentiation.","authors":"R. Wong, K. Chow","doi":"10.1002/TERA.10018","DOIUrl":"https://doi.org/10.1002/TERA.10018","url":null,"abstract":"BACKGROUND\u0000The nematode mab-21 gene specifies sensory ray cell identity and was first isolated because of its mutant sensory ray defects. Vertebrate Mab21 orthologs have since been identified in mammals and amphibians. In this report, we characterized in detail two Mab21 orthologs in mouse, Mab21l1 and Mab21l2.\u0000\u0000\u0000METHODS\u0000We examined the genomic organizations of Mab21 genes and used northern blot and in situ hybridizations to assay their temporal-spatial expression pattern. Their embryonic functions were revealed by specific attenuation of Mab21 messages with antisense oligos in cultured embryos.\u0000\u0000\u0000RESULTS\u0000Mab21l1 and Mab21l2 have very similar protein make-up and gene structures. Both genes were expressed in overlapping domains of actively differentiating embryonic tissues. In addition, Mab21l1 had unique expression in the lens vesicles and genital tubercle whereas Mab21l2 was expressed in the retinal epithelium and umbilical cord. Mab21l1 and Mab21l2 depleted embryos had severe defects in notochord, neural tube, organogenesis, vasculogenesis, and axial turning.\u0000\u0000\u0000CONCLUSIONS\u0000The findings demonstrate that both Mab21 genes are required in developing embryos for embryonic turning, formation of the notochord, neural tube, and other organ tissues.","PeriodicalId":22211,"journal":{"name":"Teratology","volume":"1 1","pages":"70-7"},"PeriodicalIF":0.0,"publicationDate":"2002-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91542436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Knowledge, use, and education regarding folic acid supplementation: continuation study of women in Colorado who had a pregnancy affected by a neural tube defect.","authors":"Janice Rinsky-Eng,&nbsp;Lisa Miller","doi":"10.1002/tera.90007","DOIUrl":"https://doi.org/10.1002/tera.90007","url":null,"abstract":"<p><strong>Background: </strong>This study was conducted to: (1) determine whether women who have had a neural tube defect (NTD) affected pregnancy know about recommendations for NTD recurrence prevention; (2) educate them about the recommendations; and (3) ensure that they have access to folic acid prior to another pregnancy.</p><p><strong>Methods: </strong>Colorado women who had an NTD affected pregnancy in 1999 or later were interviewed about their knowledge and use of folic acid, provided with verbal information about folic acid and NTD prevention, and offered written information and a voucher for free folic acid.</p><p><strong>Results: </strong>Thirty-two of 68 women who had an NTD affected pregnancy were interviewed. Of these, 22 (69%) were aware of the 0.4 mg. folic acid recommendation for women of child bearing age who have not had an NTD affected pregnancy (MMWR, '91). Only 15 (47%) of the women knew about the U.S. Public Health Service recommendation (MMWR, '92) to consume 4.0 mg of folic acid prior to another pregnancy for NTD recurrence prevention. Twenty-five (78%) of the women reported taking a multivitamin or folic acid daily.</p><p><strong>Conclusions: </strong>Nine years after national folic acid recommendations, a majority of interviewed women (53%) with NTD affected pregnancies did not know about the recommendation to consume 4.0 mg of folic acid for NTD recurrence prevention. This sample of women are receptive to information about folic acid. Health care providers and public health officials should ensure that education about folic acid is provided in an effective and timely manner to women with NTD-affected pregnancies.</p>","PeriodicalId":22211,"journal":{"name":"Teratology","volume":"66 Suppl 1 ","pages":"S29-31"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/tera.90007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21998007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of the aryl hydrocarbon receptor repressor gene and association of its Pro185Ala polymorphism with micropenis.","authors":"H. Fujita, R. Kosaki, H. Yoshihashi, T. Ogata, M. Tomita, T. Hasegawa, Takao Takahashi, N. Matsuo, K. Kosaki","doi":"10.1002/TERA.1093","DOIUrl":"https://doi.org/10.1002/TERA.1093","url":null,"abstract":"BACKGROUND Genetic background of a fetus contributes to the abnormal development after teratogen exposure. In rodents, in utero exposure to dioxins affects male external genital development. The effects of dioxins are mediated via the aryl hydrocarbon receptor (AHR) and its binding protein, aryl hydrocarbon receptor nuclear translocator (ARNT). In mice, aryl hydrocarbon receptor repressor (AHRR), which binds to ARNT in competition with AHR, plays a critical negative regulatory role in AHR signaling. We attempt to characterize the human AHRR gene and investigate the relationship between AHRR polymorphisms and the incidence of micropenis, a phenotype of undermasculinization. METHODS We identified and characterized the human homolog of mouse AHRR, taking advantage of the publicly available draft version of the human genome sequence. After detecting an AHRR protein polymorphism by the direct sequencing of pooled human genomic DNA, we evaluated the association between the polymorphism and the presence or absence of micropenis (< -2.5 SD) in patients with micropenis and control subjects. RESULTS The deduced sequence for human AHRR (715 residues) and the mouse AHRR protein exhibited 81% sequence homology to each other. The Pro185Ala polymorphism was identified between the PAS-A region and the highly conserved arginine/cysteine-rich RCFRCRL/VRC region. Forty-six percent (27/59) of patients with micropenis and 27% (22/80) of the controls were homozygous for 185Pro; this difference in frequencies was significant (P = 0.03). CONCLUSIONS Homozygosity for the 185Pro allele of AHRR may increase the susceptibility of a fetus to the undermasculinizing effects of dioxin exposure in utero, presumably through the diminished inhibition of AHR-mediated signaling.","PeriodicalId":22211,"journal":{"name":"Teratology","volume":"59 1","pages":"10-8"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74870612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}